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WE'D LIKE TO WELCOME
ALL OF 

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YOU BOTH IN THE ROOM AND 

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WATCHING US ONLY THE VIDEO CAST.

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FOR THE WORKSHOP.  MOST ARE HERE

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TODAY FROM NINE INSTITUTESES AND

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CENTERS OF THE NIH.  THE FNIH 

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AND THE FDA.  BY WAY OF SOME 

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BACKGROUND.  IT WAS ESTABLISHED 

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AS PART OF THE CURE ACT.  IT WAS

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DESIGNED TO ACCELERATE PROGRESS 

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BY SUPPORTING CLINICAL WORKSHOP 

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ON ADULT STEM CELLS.  THIS 

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REGENERATIVE MEDICINE IS AN 

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EFFORT IN COORDINATION WITH THE 

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FDA.  THE RMIP HAS FUNDED ABOUT 

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20 PROJECTS AND IT'S BEEN 

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SUCCESSFUL AS A COORDINATED 

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INITIATIVE ACROSS THE NIH 

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INSTITUTES AND CENTERS AND OTHER

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FEDERAL PARTNERS.  BUT, RMIP 

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FUNDING IS COMPLETED AND WE'RE 

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ASKING THE QUESTION, OF HOW TO 

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SUSTAIN COLLABORATION ACROSS THE

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NIH AND OTHER AGENCIES TO 

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FURTHER RESEARCH.  WITH ABOUT 

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TWO THOUSAND CLINICAL TRIALS 

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ONGOING IN REGENERATIVE MEDICINE

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WORLDWIDE EVERYONE HERE KNOWS 

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THAT REGENERATIVE MEDICINE HOLDS

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GREAT PROMISE FOR TREATING AND 

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EVEN CURING A VARIETY OF 

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INJURIES AND DISEASES BUT WE 

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ALSO KNOW THAT MORE WORK REMAINS

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TO BE DONE TOWARDS THE 

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DEVELOPMENT OF SAFE AND 

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EFFECTIVE REGENERATIVE MEDICINE 

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PRODUCTS TO REALIZE THE FULL 

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POTENTIAL OF THIS FIELD.  THE 

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NIH AND OUR FEDERAL PARTNERS ARE

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HOLDING WITH WORKSHOP TO LEARN 

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ABOUT YOUR EXPERIENCES, BOTH 

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YOUR SUCCESSES AND YOUR 

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CHALLENGES WHETHER YOU WERE 

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FUNDED BY RMIP OR NOT AND TO 

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IDENTIFY RESEARCH QUESTIONS THAT

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ARE SHARED ACROSS ISSUES AND 

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DISEASES WHERE AN NIH-WIDE 

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APPROACH WOULD BE VALUABLE AND 

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I'M NOW GOING TO TURN THE 

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MEETING OVER TO BOB CARTER FOR 

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HIS REMARKS INVOLVING THE 

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WORKSHOP.

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>> BOB CARTER: THANK YOU. 
AND 

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REALLY GLAD TO SEE EVERYBODY 

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HERE.  THIS MEETING GOT PLANNED 

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ON A VERY FAST TIMELINE AND IT'S

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WONDERFUL THAT WE MANAGED TO GET

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YOU ALL HERE.  AND LOOK FORWARD 

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TO WHAT YOU HAVE TO SAY AND I 

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THINK SHE CAPTURED WHAT WE'RE 

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TRYING TO DO BUT I WANT TO 

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EMPHASIZE A COUPLE POINTS.  

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FIRST OF ALL, LET'S HAVE THE 

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MEMBERS OF THE WORKING GROUP WHO

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ARE HERE, STAND UP.  SO THESE

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-- THERE'S THE KIND OF MEDICINES

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WHERE YOU GIVE PEOPLE PILLS OR 

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ANTIBIOTICS OR WHATEVER AND THEN

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THERE'S SURGERY AND THEN THERE'S

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REYEN RAHTIVE MEDICINE AND I 

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THINK WE CAN ALL AGREE THAT THE 

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BEST OUTCOME FROM ANY INJURY OR 

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DISEASE WOULD BE TO REGROW 

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HEALTHY TISSUE AND THAT'S REALLY

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WHAT WE'RE ABOUT.  SO WHAT ARE 

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THE CHALLENGES AND HOW DO WE 

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MEET THEM SO THAT WE CAN GET 

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MORE OF REGENERATIVE MEDICINE 

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APPROACHES TO BE USED IN THE 

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CLINIC.  AT A SCALE THAT'S 

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FEASIBLE AND A COST THAT DOESN'T

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PRECLUDE A LOT OF PEOPLE FROM 

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RECEIVING IT?  THAT'S ACTUALLY A

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BIG CHALLENGE.  AND WE'RE 

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ACTUALLY STILL A GOOD WAYS FROM 

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THAT.  IN PART BECAUSE A LOT OF 

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THIS IS PERSONALIZED.  IN PART 

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BECAUSE IT'S NEW IN PART BECAUSE

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IT'S CELLS WHICH IS A LOT 

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DIFFERENT THAN AN ANTIBODY AND 

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IN PART BECAUSE SOMETIMES WE 

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MANIPULATE THE CELLS AND WE HAVE

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TO BE CAREFUL WHAT DID WE 

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PRODUCE IN THE TEST TUBE?  SO 

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THE POINT TO THINK ABOUT, THE 

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SORT OF FRAME OF REFERENCE IS 

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NOT JUST WHAT IS THE NEXT 

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EXPERIMENT FOR MY LAB BUT WHAT'S

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THE THING THAT NIH CENTERS AND 

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INSTITUTES CAN DO TOGETHER TO 

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MOVE THIS WHOLE FIELD FORWARD?  

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THAT'S NOT TO SAY WE DON'T WANT 

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TO LOOK AT INDIVIDUAL PROJECTS 

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BUT WE WANT TO LOOK AT 

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INDIVIDUAL PROJECTS IN THAT 

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CONTEXT.  SO THERE MAY BE SOME 

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REYEN RAHTIVE MEDICINE APPROACH 

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THAT ACTUALLY HAS SOME 

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SIMILARITIES.  BECAUSE YOU HAVE 

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TO MAINTAIN CELLS AND SOMETIMES 

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MANIPULATE THEM.  WHAT CAN WE 

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LEARN FROM DOING THAT IN 

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DIFFERENT SYSTEMS? SO THE EXACT 

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APPROACHES, EXACTLY, WE TAKE AN 

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IPS CELL, HOW DO YOU REPAIR AN 

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ORGAN BUT HOW DO YOU ASSESS 

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WHETHER WHAT YOU PRODUCED IS THE

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RIGHT THING, ITS QUALITY 

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ASSURANCE WHETHER IT'S NOT GOING

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TO KILL SOMEBODY WHICH IS NOT 

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TRIVIAL AND THAT IT'S GOING TO 

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WORK FOR EVERYTHING THAT YOU 

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PRODUCE.  IS KIND OF A SHARED 

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QUESTION THAT GOES ACROSS ALL OF

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REGENERATIVE MEDICINE SO IT 

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CAN -- IN MY MIND I DO THINK OF 

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SPECIFIC PROJECTS THAT WE MIGHT 

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THINK ABOUT THAT WE MIGHT 

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ULTIMATELY WANT TO FUND SOZ R 

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SORT OF AS WE DID WITH MRP SO WE

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TAKE STEM CELLS AND LOOK AT THE 

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JOINT OR CARDIAC TISSUE OR 

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RETINA.  AS LONG AS THOSE 

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PROJECTS ARE DESIGNED SUCH THAT 

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THEY WOULD PRODUCE DATA THAT 

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WOULD ENABLE ALL THOSE DIFFERENT

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APPROACHES TO MOVE FORWARD 

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FASTER.  AND, IN FACT, AT A 

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RECENT NATIONAL ACADEMIES 

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CONFERENCE ON THEIR REGENERATIVE

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MEDICINE PARTIALLY ORGANIZED BY 

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CHRIS ROY WHO IS ONE OF THE 

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ORGANIZERS OF THIS MEETING BUT 

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COULDN'T TRAVEL LOOKED AT 

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MANUFACTURING AND THE THING THAT

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CAME OUT WAS HOW DO YOU DO 

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QUALITY ASSURANCE AT THE END 

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AFTER YOU PRODUCED YOUR PRODUCT 

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HOW DO YOU MAKE SURE THAT IT'S 

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FIT FOR PURPOSE?  AND THAT -- HE

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WAS ACTUALLY -- CAME OUT OF THAT

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MEETING AS PROBABLY ONE OF THE 

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BIGGEST HOLDUPS BECAUSE ACTUALLY

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AS A CLINICIAN YOU WANT TO BE 

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SURE BUT ALSO FOR REGULATORY 

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PURPOSES YOU HAVE TO BE SURE.  

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CAN WE PRODUCE DATA TO ALLOW US 

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TO GET A BETTER IDEA OF WHAT ARE

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THE CHARACTERISTICS OF THE 

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THINGS THAT WE PRODUCE THAT MAKE

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THEM FIT FOR PURPOSE?  SO IT MAY

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BE BASED ON INDIVIDUAL PROJECTS 

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WITH SPECIFIC CELLS AND SPECIFIC

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TISSUES BUT IF IT CAN HELP US 

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GET THE DATA THAT WE CAN USE AND

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PERHAPS WE'RE GOING TO BE HEADED

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TOWARDS MACHINE LEARNING TO 

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UNDERSTAND WHAT THE PARAMETERS 

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ARE THAT ACTUALLY DETERMINE 

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WHETHER SOMETHING IS FIT FOR 

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PURPOSE, WHAT WE MIGHT BE ABLE 

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TO DO IS HELP GENERATE THE DATA 

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THAT CAN BE THEN APPLIED TO 

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ANSWER THOSE QUESTIONS TO SPEED 

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THINGS THROUGH, BOTH MOVE FROM 

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MANUFACTURING AND INTO THE 

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PATIENT AND THE REGULATORY 

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PROCESS.  SO I HOPE I'M TRYING 

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TO DESCRIBE SORT OF A THOUGHT 

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FRAMEWORK THAT WE HAVE TO KEEP 

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IN MIND TODAY.  SO THERE ARE TWO

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DIFFERENT GOALS.  THIS, THE IDEA

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FOR THIS MEETING CAME OUT OF 

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REGENERATIVE MEDICINE INNOVATION

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PROJECT AND THE IDEA WAS WE 

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FUNDED A LOT OF RESEARCH, 

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DIFFERENT STAGES OF PRECLINICAL 

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ALL THE WAY TO CLINICAL TRIALS. 

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AND SOME OF THEM ARE ONGOING NOW

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RECENTLY FUNDED A YEAR AGO.  BUT

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WHAT CAN WE LEARN FROM THIS?  

192
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AND HOW DO WE SUSTAIN THE 

193
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MOMENTUM OF REGENERATIVE 

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MEDICINE INNOVATION PROJECT OF 

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BRINGING THE NIH INSTITUTES AND 

196
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CENTERS TOGETHER AND WHAT ARE 

197
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THE PLACES WHERE WE CAN FIND 

198
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COMMON GROUND?  AND AS I'VE 

199
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DESCRIBED, A LOT OF THINGS MAY 

200
00:09:23,178 --> 00:09:27,849
BE ONE-OFF PROJECTS THROUGH 

201
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THERE SHOULD BE SHARED LEARNING 

202
00:09:29,351 --> 00:09:31,186
ACROSS THEM.  THROUGH THE 

203
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EFFORTS ACTUALLY I WILL GIVE 

204
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CREDIT TO SUSANNA STEIN AND TONY

205
00:09:35,957 --> 00:09:38,026
STARTED THINKING ABOUT WHAT ARE 

206
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THE OPPORTUNITY TO ACTUALLY DO 

207
00:09:39,294 --> 00:09:39,928
SOMETHING HERE 

208
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AND THAT RELATED TO THE 

209
00:09:43,665 --> 00:09:44,366
ACCELERATING MEDICINES 

210
00:09:44,366 --> 00:09:47,903
PARTNERSHIP RUN THROUGH FNIH AND

211
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COURTNEY S HERE IS THE 

212
00:09:49,404 --> 00:09:52,274
REPRESENTATIVE AND ACTUALLY IN 

213
00:09:52,274 --> 00:09:56,077
CHARGE OF OF THE PARTNERSHIP AND

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00:09:56,077 --> 00:09:57,846
THEY HAD THE BESPOKE CONSORTIUM 

215
00:09:57,846 --> 00:09:59,981
AND WHAT THAT GROUP DID WAS 

216
00:09:59,981 --> 00:10:01,249
DIFFERENT FROM THE OTHER 

217
00:10:01,249 --> 00:10:02,918
PARTNERSHIP.  IT TOOK WHAT THEY 

218
00:10:02,918 --> 00:10:04,019
CALLED A PLATFORM THEY TOOK A 

219
00:10:04,019 --> 00:10:06,187
SINGLE APPROACH AND FOCUSED ON 

220
00:10:06,187 --> 00:10:08,189
IT WITHOUT REALLY THINKING 

221
00:10:08,189 --> 00:10:09,724
BEFOREHAND WHAT IS THE DISEASE 

222
00:10:09,724 --> 00:10:11,760
AND CONDITION WHICH IS THE EXACT

223
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OPPOSITE OF MOST OF THE 

224
00:10:13,628 --> 00:10:14,496
ACCELERATING MEDICINES PROJECT 

225
00:10:14,496 --> 00:10:17,198
BUT THEY DECIDED IF YOU COULD 

226
00:10:17,198 --> 00:10:20,869
REALLY IMPROVE AAV THERAPY THAT 

227
00:10:20,869 --> 00:10:21,870
WOULD BENEFIT EVERYBODY AND THEY

228
00:10:21,870 --> 00:10:23,705
TOOK TWO APPROACHES ONE WAS HOW 

229
00:10:23,705 --> 00:10:25,907
DO YOU MAKE A BETTER AAV AND THE

230
00:10:25,907 --> 00:10:28,944
OTHER IS HOW DO YOU MAKE IT IN 

231
00:10:28,944 --> 00:10:30,645
THE, YOU KNOW, IN -- MANUFACTURE

232
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IT AND WITH THOSE TWO FOCUSES SO

233
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IT'S A PLATFORM APPROACH AND 

234
00:10:35,350 --> 00:10:38,353
THEN THEY TAKE THOSE TWO SORT OF

235
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GOALS FUNDED NOW A BUNCH OF 

236
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CLINICAL TRIALS IN DIFFERENT 

237
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DISEASES BY EACH WITH THAT 

238
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PURPOSE OF UNDERSTANDING THOSE 

239
00:10:46,061 --> 00:10:47,929
BOTH THE BASIC BIOLOGY. 

240
00:10:47,929 --> 00:10:51,099
OR HOW DO YOU MANUFACTURE IT TO 

241
00:10:51,099 --> 00:10:54,736
MAKE IT MORE UNIFORM BETTER 

242
00:10:54,736 --> 00:11:01,676
PROJECT?  SO I THINK THAT'S 

243
00:11:01,676 --> 00:11:03,278
WHERE WE WANT TO DEVELOP.  WE 

244
00:11:03,278 --> 00:11:04,145
SPOKE TO THE BESPOKE GENE 

245
00:11:04,145 --> 00:11:06,081
THERAPY AND SAID YOU HAVE A NICE

246
00:11:06,081 --> 00:11:08,917
PLATFORM HERE FOR TESTING THIS 

247
00:11:08,917 --> 00:11:10,819
APPROACH.  BUT THE AAV IS KIND 

248
00:11:10,819 --> 00:11:13,221
OF RESTRICTED TO ONE PLACE THAT 

249
00:11:13,221 --> 00:11:14,456
WE MAY NOT EVEN THINK IS THE 

250
00:11:14,456 --> 00:11:16,758
BEST ONE FOR THE FUTURE.  CAN WE

251
00:11:16,758 --> 00:11:19,628
BUILD ON THAT?  CAN WE USE THAT 

252
00:11:19,628 --> 00:11:21,663
PLATFORM TO LOOK AT OTHER 

253
00:11:21,663 --> 00:11:24,099
APPROACHES? AND THE ANSWER WAS 

254
00:11:24,099 --> 00:11:27,268
THEY HAD THEIR HANDS FULL.  THEY

255
00:11:27,268 --> 00:11:29,137
DIDN'T WANT TO BROAD -- THE 

256
00:11:29,137 --> 00:11:31,039
BESPOKE GENE THERAPY CONSORTIUM 

257
00:11:31,039 --> 00:11:32,841
BUT THEY DID -- WERE WILLING TO 

258
00:11:32,841 --> 00:11:34,209
WORK WITH US AS SORT OF A 

259
00:11:34,209 --> 00:11:35,777
PARALLEL PROCESS TO TAKE THAT 

260
00:11:35,777 --> 00:11:38,647
IDEA OF A PLATFORM, TO TAKE THE 

261
00:11:38,647 --> 00:11:40,582
WAY THEY STRUCTURED IT, THE WAY 

262
00:11:40,582 --> 00:11:43,385
THEY SET UP A THEME TO FIND THE 

263
00:11:43,385 --> 00:11:46,488
THEME AND THEN FUNDED CLINICAL 

264
00:11:46,488 --> 00:11:47,288
TRIALS WITHIN THOSE THEMES SO 

265
00:11:47,288 --> 00:11:49,391
THAT'S WHERE WE'RE HEADED NOW 

266
00:11:49,391 --> 00:11:51,693
FOR THE CELL BASED THERAPIES 

267
00:11:51,693 --> 00:11:55,096
CONSORTIUM THE GOOD NEWS IS THAT

268
00:11:55,096 --> 00:11:58,433
THE EXECUTIVE COMMITTEE FOR THE 

269
00:11:58,433 --> 00:12:00,235
OVERALL ACCELERATED MEDICINES 

270
00:12:00,235 --> 00:12:03,805
PROJECT HAS APPROVED CBTC.  CELL

271
00:12:03,805 --> 00:12:07,008
BASED THERAPIES CONSORTIUM AS A 

272
00:12:07,008 --> 00:12:09,511
CONCEPT WITHIN THE ACCELERATING 

273
00:12:09,511 --> 00:12:11,146
MEDICINES PARTNERSHIP WHAT THAT 

274
00:12:11,146 --> 00:12:14,015
MEANS IS COURTNEY'S TEAM WORKS 

275
00:12:14,015 --> 00:12:15,350
TO PUT TOGETHER THE DIFFERENT 

276
00:12:15,350 --> 00:12:16,818
STAKEHOLDERS AND SEE WHO CAN 

277
00:12:16,818 --> 00:12:18,486
HELP DESIGN THE PROTOCOL, 

278
00:12:18,486 --> 00:12:20,121
ADDRESS THE QUESTION OF WHAT'S 

279
00:12:20,121 --> 00:12:22,323
THIS PLATFORM GOING TO BE AND 

280
00:12:22,323 --> 00:12:26,761
HOW DO WE APPROACH IT?  

281
00:12:26,761 --> 00:12:28,530
ALTERNATIVELY THOUGH WE HAVE TO 

282
00:12:28,530 --> 00:12:30,465
GET A PROTOCOL THAT WILL BE OF 

283
00:12:30,465 --> 00:12:32,133
INTEREST TO MULTIPLE DIFFERENT 

284
00:12:32,133 --> 00:12:34,869
STAKEHOLDERS THAT INCLUDE NIH, 

285
00:12:34,869 --> 00:12:36,071
FDA BUT ALSO INDUSTRY AND IT 

286
00:12:36,071 --> 00:12:36,971
WILL BE A PARTNERSHIP BETWEEN 

287
00:12:36,971 --> 00:12:38,640
THOSE GROUPS WITH FUNDING FROM 

288
00:12:38,640 --> 00:12:40,208
BOTH THOSE GROUPS IF IT'S GOING 

289
00:12:40,208 --> 00:12:42,077
TO WORK.  IN OTHER WORDS, 

290
00:12:42,077 --> 00:12:43,878
NOTHING'S GOING TO MOVE FORWARD 

291
00:12:43,878 --> 00:12:45,547
THAT IS NOT OF INTEREST ACROSS 

292
00:12:45,547 --> 00:12:47,315
THOSE DIFFERENT GROUPS.  SO WE 

293
00:12:47,315 --> 00:12:49,818
HAVE TO KEEP THAT THOUGHT IN OUR

294
00:12:49,818 --> 00:12:52,153
HEAD.  WHAT IS THE PLATFORM THAT

295
00:12:52,153 --> 00:12:55,356
WE CAN USE TO ADVANCE CELL BASED

296
00:12:55,356 --> 00:12:56,558
THERAPIES THAT WILL BE BROADLY 

297
00:12:56,558 --> 00:13:00,428
OF INTEREST TO THOSE DIFFERENT 

298
00:13:00,428 --> 00:13:01,730
STAKEHOLDERS.  SO WE'RE DOING 

299
00:13:01,730 --> 00:13:03,631
PRETTY WELL.  THAT'S THE MESSAGE

300
00:13:03,631 --> 00:13:04,733
I WANT TO DELIVER.  IF THERE ARE

301
00:13:04,733 --> 00:13:09,003
ANY QUESTIONS ABOUT WHAT I JUST 

302
00:13:09,003 --> 00:13:13,408
SAID?  WELL, EITHER YOU ARE 

303
00:13:13,408 --> 00:13:17,779
REALLY CONFUSED OR -- SO WE ARE 

304
00:13:17,779 --> 00:13:19,581
GOING TO START WITH WHAT WAS THE

305
00:13:19,581 --> 00:13:21,816
INITIAL SORT OF IMPETUS FOR THIS

306
00:13:21,816 --> 00:13:24,419
MEETING.  WHICH IS TO THINK 

307
00:13:24,419 --> 00:13:27,355
ABOUT HOW NIH INSTITUTES AND 

308
00:13:27,355 --> 00:13:29,457
CENTERS CAN WORK TOGETHER TO 

309
00:13:29,457 --> 00:13:33,461
ADVANCE REGENERATIVE MEDICINE.  

310
00:13:33,461 --> 00:13:36,131
AND THE -- AS WE SAID, WHAT WE 

311
00:13:36,131 --> 00:13:37,565
WANTED TO DO INITIALLY WAS BRING

312
00:13:37,565 --> 00:13:40,068
TOGETHER THE RMIP INVESTIGATORS 

313
00:13:40,068 --> 00:13:41,903
TO TELL US ABOUT THEIR 

314
00:13:41,903 --> 00:13:42,570
EXPERIENCE OF LESSONS LEARNED, 

315
00:13:42,570 --> 00:13:45,507
OF WHAT HAS WORKED, WHAT HASN'T 

316
00:13:45,507 --> 00:13:46,641
AND THINK ABOUT COMMON 

317
00:13:46,641 --> 00:13:47,575
CHALLENGES GOING FORWARD.  

318
00:13:47,575 --> 00:13:49,377
HAVING DESIGNED THE MEETING WITH

319
00:13:49,377 --> 00:13:51,880
THAT AS THE INITIAL GOAL, WE 

320
00:13:51,880 --> 00:13:54,382
THEN SAID, WELL, WAIT A MINUTE, 

321
00:13:54,382 --> 00:13:55,350
THERE ARE OTHER PEOPLE IN 

322
00:13:55,350 --> 00:13:56,384
REGENERATIVE MEDICINE WHO ALSO 

323
00:13:56,384 --> 00:13:58,086
MIGHT HELP US ANSWER THOSE 

324
00:13:58,086 --> 00:14:01,356
QUESTIONS AND SO WE BEGAN 

325
00:14:01,356 --> 00:14:04,559
INVITING A BUNCH OF OTHER 

326
00:14:04,559 --> 00:14:08,997
INVESTIGATOR WHO IS WERE NOT 

327
00:14:08,997 --> 00:14:11,933
FUNDED BY RMIP BUT COULD HELP 

328
00:14:11,933 --> 00:14:13,067
ABOUT SHARED INTERESTS GOING 

329
00:14:13,067 --> 00:14:14,669
FORWARD SO THE FIRST TWO 

330
00:14:14,669 --> 00:14:16,571
SESSIONS ARE ON THOSE BASIS.  

331
00:14:16,571 --> 00:14:18,406
AND WE HAVE TWELVE SPEAKERS IN 

332
00:14:18,406 --> 00:14:22,477
THE FIRST ONE, ALL FROM RMIP.  

333
00:14:22,477 --> 00:14:24,512
AND WE HAVE AN HOUR AND A HALF 

334
00:14:24,512 --> 00:14:26,447
SO THE TIME IS POSSIBLE IF 

335
00:14:26,447 --> 00:14:27,749
PEOPLE KEEP THEIR REMARKS TO 

336
00:14:27,749 --> 00:14:30,518
FIVE MINUTES WHICH IS WHAT THEY 

337
00:14:30,518 --> 00:14:34,255
WERE ASKED TO DO.  AND MY 

338
00:14:34,255 --> 00:14:36,891
CO-CHAIR FAY WONG WILL HELP 

339
00:14:36,891 --> 00:14:39,060
POLICE THIS.  IN FOUR MINUTES 

340
00:14:39,060 --> 00:14:41,329
SHE'LL HOLD UP A CARD AND AT 

341
00:14:41,329 --> 00:14:44,199
TIME ZERO WHEN FIVE MINUTES ARE 

342
00:14:44,199 --> 00:14:46,434
UP SHE WILL INTERFERE POLITELY 

343
00:14:46,434 --> 00:14:48,136
AND SHE'S VERY QUIET AND 

344
00:14:48,136 --> 00:14:51,573
RESERVED AND I HATE TO SAY IT 

345
00:14:51,573 --> 00:14:53,942
BUT THAT'S A JOKE.  SO TALK 

346
00:14:53,942 --> 00:14:56,244
ABOUT GOOD COP BAD COP I GOT THE

347
00:14:56,244 --> 00:14:59,314
GREAT BAD COP.  SO WE DO WANT TO

348
00:14:59,314 --> 00:15:00,915
TRY TO KEEP THAT ON TRACK.  

349
00:15:00,915 --> 00:15:01,783
OBVIOUSLY WHAT WE'RE GOING TO DO

350
00:15:01,783 --> 00:15:03,618
IS TRANSITIONS WILL NEED TO BE 

351
00:15:03,618 --> 00:15:05,386
QUICK AND THANK YOU, ALL, FOR 

352
00:15:05,386 --> 00:15:07,856
GETTING YOUR SLIDES.  WHERE IS 

353
00:15:07,856 --> 00:15:10,425
JANNA?  IS SHE STEPPED OUT?  

354
00:15:10,425 --> 00:15:12,026
GOOD BECAUSE JANNA IS THE HERO 

355
00:15:12,026 --> 00:15:15,496
OF THIS WHOLE THING.  SHE WAS AN

356
00:15:15,496 --> 00:15:18,833
ANALYST AND WITHOUT HER EFFORTS 

357
00:15:18,833 --> 00:15:20,368
PULLING THIS THING TOGETHER IT 

358
00:15:20,368 --> 00:15:23,004
WOULD NOT HAVE HAPPENED SOME OF 

359
00:15:23,004 --> 00:15:25,540
YOU WERE BRINGING SLIDES TO HER 

360
00:15:25,540 --> 00:15:26,774
ONLY TEN MINUTES AGO.  SOME OF 

361
00:15:26,774 --> 00:15:29,210
YOU MAY BE E-MAILING SLIDES TO 

362
00:15:29,210 --> 00:15:30,712
HER NOW SO WE HOPE THE ORDER 

363
00:15:30,712 --> 00:15:32,547
WORKS OUT AND WE HOPE WE GET THE

364
00:15:32,547 --> 00:15:33,481
RIGHT SLIDE SET IN FACT SOME OF 

365
00:15:33,481 --> 00:15:36,251
THE TITLES HAVE CHANGED, SO WHAT

366
00:15:36,251 --> 00:15:37,952
WE'RE GOING TO DO IS GO PRETTY 

367
00:15:37,952 --> 00:15:38,686
QUICKLY THROUGH THAT.  IF WE 

368
00:15:38,686 --> 00:15:40,421
HAVE TIME AT THE END, WE CAN 

369
00:15:40,421 --> 00:15:41,756
START TO SAY, OKAY, WHAT WERE 

370
00:15:41,756 --> 00:15:46,394
THE THEMES THAT WE HEARD?  WHAT 

371
00:15:46,394 --> 00:15:49,063
WERE THE THINGS THAT RESONATE AS

372
00:15:49,063 --> 00:15:52,233
CROSS NIH PROJECTS COMING OUT OF

373
00:15:52,233 --> 00:15:53,902
MEDICINE?  THESE INVESTIGATORS 

374
00:15:53,902 --> 00:15:55,336
HAVE BEEN WORKING IN A PROGRAM 

375
00:15:55,336 --> 00:15:58,573
WHICH IS -- WHICH OPERATES 

376
00:15:58,573 --> 00:16:00,241
ACROSS NIH WHERE HAS THAT 

377
00:16:00,241 --> 00:16:03,878
WORKED? WE KNOW THAT THE 

378
00:16:03,878 --> 00:16:05,213
NEGATIVES, RMIP REQUIRED 

379
00:16:05,213 --> 00:16:07,081
MATCHING FRONTS FROM SOMEBODY 

380
00:16:07,081 --> 00:16:10,418
OUTSIDE OF NIH EITHER THE HOST 

381
00:16:10,418 --> 00:16:12,453
SOLUTION AND SOMETIMES ADVOCACY 

382
00:16:12,453 --> 00:16:14,489
ORGANIZATIONS.  THAT OBVIOUSLY 

383
00:16:14,489 --> 00:16:17,091
WAS A PRETTY BIG IMPEDIMENT.  WE

384
00:16:17,091 --> 00:16:19,494
KNOW THINGS LIKE THAT SO REALLY 

385
00:16:19,494 --> 00:16:20,895
KEEP THE QUESTION FOCUSED ON THE

386
00:16:20,895 --> 00:16:23,398
FUTURE OF HOW WE WORK TOGETHER. 

387
00:16:23,398 --> 00:16:25,233
THE SECOND SESSION WILL BE THE 

388
00:16:25,233 --> 00:16:27,235
SPEAKERS FROM OUTSIDE OF RMIP 

389
00:16:27,235 --> 00:16:29,270
THAT REALLY STILL FOCUSED ON 

390
00:16:29,270 --> 00:16:31,239
THAT INITIAL QUESTION.  OF HOW 

391
00:16:31,239 --> 00:16:33,374
CAN NIH INSTITUTES AND CENTERS 

392
00:16:33,374 --> 00:16:35,910
WORK TOGETHER TO ADVANCE THIS 

393
00:16:35,910 --> 00:16:37,345
FIELD?  AT THAT POINT WE THEN 

394
00:16:37,345 --> 00:16:39,213
START TO SHIFT.  AND WE'LL BRING

395
00:16:39,213 --> 00:16:41,983
IN SOME OTHER SPEAKERS FROM -- 

396
00:16:41,983 --> 00:16:44,919
WHO ARE NOT INVESTIGATORS BUT IN

397
00:16:44,919 --> 00:16:46,120
OTHER CASES ADVOCATE 

398
00:16:46,120 --> 00:16:48,189
ORGANIZATIONS, INDUSTRY 

399
00:16:48,189 --> 00:16:48,756
REPRESENTATIVES, SOMETIMES 

400
00:16:48,756 --> 00:16:52,593
ORGANIZATIONS THAT ARE FUNDED BY

401
00:16:52,593 --> 00:16:54,228
INDUSTRY TO FORWARD THEIR 

402
00:16:54,228 --> 00:16:55,596
INTEREST.  AND HEAR THEIR 

403
00:16:55,596 --> 00:16:56,764
PERSPECTIVES SO THAT WE KEEP 

404
00:16:56,764 --> 00:16:58,266
THAT IN MIND BEFORE WE START 

405
00:16:58,266 --> 00:17:01,035
GETTING INTO DETAILS OF WHAT WE 

406
00:17:01,035 --> 00:17:03,571
MIGHT DO WITHIN CELL BASED 

407
00:17:03,571 --> 00:17:04,505
THERAPIES CONSORTIUM AND THEN 

408
00:17:04,505 --> 00:17:07,575
TALK ABOUT THE FDA ABOUT THEIR 

409
00:17:07,575 --> 00:17:08,943
PERSPECTIVES ON WHAT THE NEEDS 

410
00:17:08,943 --> 00:17:11,279
ARE AND THEN GET INTO THE 

411
00:17:11,279 --> 00:17:15,116
SESSIONS ON TWO TOPICS THAT WE 

412
00:17:15,116 --> 00:17:18,486
THINK MIGHT BE RIGHT.  ONE ON 

413
00:17:18,486 --> 00:17:21,222
TISSUE SPECIFIC STEM CELLS AND 

414
00:17:21,222 --> 00:17:24,926
THEN ONE ON IPSCS.  THAT DOESN'T

415
00:17:24,926 --> 00:17:27,195
MEAN THAT THESE ARE OUR ONLY 

416
00:17:27,195 --> 00:17:29,831
INTERESTS.  SO WHAT WE TALKED 

417
00:17:29,831 --> 00:17:33,034
ABOUT IN A LOT OF OUR OTHER 

418
00:17:33,034 --> 00:17:34,502
OPPORTUNITIES, FOR EXAMPLE, 

419
00:17:34,502 --> 00:17:35,870
ORGANOIDS AND MAYBE WE WILL BE 

420
00:17:35,870 --> 00:17:36,904
ABLE TO ORGANIZE SOMETHING 

421
00:17:36,904 --> 00:17:39,741
AROUND ORGAN NOISE IN THE 

422
00:17:39,741 --> 00:17:40,174
FUTURE.  

423
00:17:40,174 --> 00:17:42,643
BUT WE WILL THEN END WITH A 

424
00:17:42,643 --> 00:17:44,312
GROUP DISCUSSION OF WHAT ARE THE

425
00:17:44,312 --> 00:17:46,481
THINGS WE HEARD, WHAT DO WE 

426
00:17:46,481 --> 00:17:48,950
THINK AS A GROUP IS RIGHT FOR 

427
00:17:48,950 --> 00:17:50,418
CELL BASED THERAPIES CONNOISSEUR

428
00:17:50,418 --> 00:17:52,487
SHIM AS A PLATFORM. 

429
00:17:52,487 --> 00:17:54,322
AND THEN AT -- ACTUALLY WE'RE 

430
00:17:54,322 --> 00:17:55,857
GOING TO CHANGE THE AGENDA TO 

431
00:17:55,857 --> 00:18:00,061
ONE PLACE.  NIH INSTITUTES AND 

432
00:18:00,061 --> 00:18:02,263
CENTERS LISTEN, WANT TO LEARN 

433
00:18:02,263 --> 00:18:04,632
FROM YOU, BUT WE HAVE TO BE 

434
00:18:04,632 --> 00:18:07,435
CAREFUL THAT WE DON'T TRY TO USE

435
00:18:07,435 --> 00:18:09,437
YOUR INFORMATION TO ACTUALLY 

436
00:18:09,437 --> 00:18:10,605
START WRITING FUNDING 

437
00:18:10,605 --> 00:18:12,073
OPPORTUNITY ANNOUNCEMENTS WE 

438
00:18:12,073 --> 00:18:13,808
CAN'T GIVE ANYBODY A HEAD START 

439
00:18:13,808 --> 00:18:16,644
NOW WE ARE VIDEO CAST, THIS IS 

440
00:18:16,644 --> 00:18:18,679
PUBLIC.  BUT WE DECIDED TO MAKE 

441
00:18:18,679 --> 00:18:21,549
THE -- ACTUALLY WHAT HAD BEEN 

442
00:18:21,549 --> 00:18:22,483
THE FINAL SESSION THE CLOSE 

443
00:18:22,483 --> 00:18:27,121
SESSION JUST SO THAT THE NIH CAN

444
00:18:27,121 --> 00:18:28,523
MEET AND TALK ABOUT WHAT THEY 

445
00:18:28,523 --> 00:18:30,625
HEARD AS OF THING.  SO WE MIGHT 

446
00:18:30,625 --> 00:18:32,960
CHANGE THE AGENDA JUST A LITTLE 

447
00:18:32,960 --> 00:18:39,133
BIT THERE.  WHEN WITH THAT, WE 

448
00:18:39,133 --> 00:18:41,269
CAN LAUNCH INTO SESSION ONE.  

449
00:18:41,269 --> 00:18:48,676
SO, AGAIN, AS I HEARD FROM YAN 

450
00:18:48,676 --> 00:18:50,144
 -- JANNA, SOME OF THE TITLES 

451
00:18:50,144 --> 00:18:51,145
HAVE CHANGED. 

452
00:18:51,145 --> 00:18:52,580
AND I WILL READ OUT THE NAME OF 

453
00:18:52,580 --> 00:18:54,215
THE SPEAKER AND THE SPEAKER 

454
00:18:54,215 --> 00:18:55,583
AFTER THAT.  HOPEFULLY THE 

455
00:18:55,583 --> 00:18:57,585
SPEAKER WILL COME FORWARD AND 

456
00:18:57,585 --> 00:18:59,320
THE ONE WHO IS ON DECK CAN COME 

457
00:18:59,320 --> 00:19:00,855
AND HANG OUT SO THEY'LL BE READY

458
00:19:00,855 --> 00:19:03,191
TO GO AS SOON AS THE FIRST 

459
00:19:03,191 --> 00:19:04,792
SPEAKER'S DONE.  JANNA, DO YOU 

460
00:19:04,792 --> 00:19:15,336
HAVE -- OKAY.  JANNA DIDN'T GET 

461
00:19:16,604 --> 00:19:18,840
EMBARRASSED BECAUSE SHE WASN'T 

462
00:19:18,840 --> 00:19:25,079
IN THE ROOM WHEN I WAS SINGING 

463
00:19:25,079 --> 00:19:35,590
PRAISES.  UNBELIEVABLE WE'VE 

464
00:19:56,344 --> 00:20:02,283
GOTTEN THIS FAR.  SO THE FIRST 

465
00:20:02,283 --> 00:20:05,887
SPEAKER IS G AND AFTER THAT IS 

466
00:20:05,887 --> 00:20:08,456
DENNIS SO IS THERE A MICROPHONE,

467
00:20:08,456 --> 00:20:13,528
DENNIS, CAN YOU GET UP ON THE 

468
00:20:13,528 --> 00:20:15,563
PODIUM OR ARE WE GOING TO NEED A

469
00:20:15,563 --> 00:20:17,532
MICROPHONE?  MAYBE JUST PULL UP 

470
00:20:17,532 --> 00:20:19,000
A CHAIR UP HERE?  SO, YES, 

471
00:20:19,000 --> 00:20:29,544
THEY'RE BRINGING IT UP.  OKAY.  

472
00:20:33,948 --> 00:20:36,350
THE FLOOR IS YOURS.

473
00:20:36,350 --> 00:20:38,686
>> GOOD MORNING, I WOULD
LIKE TO

474
00:20:38,686 --> 00:20:39,820
THANK THE ORGANIZERS FOR 

475
00:20:39,820 --> 00:20:42,390
ORGANIZING THIS MEETING AND FOR 

476
00:20:42,390 --> 00:20:45,193
INVITING ME TO BE HERE.  SO WE 

477
00:20:45,193 --> 00:20:47,728
WERE ASKED TO ANSWER THREE 

478
00:20:47,728 --> 00:20:49,997
QUESTIONS.  THE FIRST ONE WAS 

479
00:20:49,997 --> 00:20:55,069
WHAT IS RMIP FUNDING ALLOW YOU 

480
00:20:55,069 --> 00:20:56,771
TO ACCOMPLISH THAT WOULD BE 

481
00:20:56,771 --> 00:20:57,905
DIFFICULT OTHERWISE AND WE WERE 

482
00:20:57,905 --> 00:21:01,542
ABLE WITH THIS FUNDING TO 

483
00:21:01,542 --> 00:21:04,779
ISOLATE AND DETECT WHAT WOULD BE

484
00:21:04,779 --> 00:21:10,017
THE BEST CELLULAR PLATFORM TO 

485
00:21:10,017 --> 00:21:14,322
MODIFY WITH BIO ENGINEERED GENE 

486
00:21:14,322 --> 00:21:19,193
TO PROVIDE FACTOR EIGHT PROTEIN 

487
00:21:19,193 --> 00:21:21,996
TO TISSUES SO WE MANUFACTURED 

488
00:21:21,996 --> 00:21:25,333
AND TESTED THIS NEW REGENERATIVE

489
00:21:25,333 --> 00:21:28,336
MEDICINE PRODUCT THAT WAS 

490
00:21:28,336 --> 00:21:30,471
DESIGNED TO SPECIFICALLY TREAT 

491
00:21:30,471 --> 00:21:33,274
HEMOPHILIA A PRIOR TO BIRTH WE 

492
00:21:33,274 --> 00:21:35,076
TEST THE THERAPEUTIC POTENTIAL 

493
00:21:35,076 --> 00:21:36,577
OF THIS PRODUCT IN A LARGE 

494
00:21:36,577 --> 00:21:40,848
ANIMAL MODEL AND THE PRODUCT 

495
00:21:40,848 --> 00:21:44,485
CONSISTED OF CELLS TRANSDUCED 

496
00:21:44,485 --> 00:21:48,856
WITH THE TRANSGENE A GENE THAT 

497
00:21:48,856 --> 00:21:50,224
PRODUCES FACTOR EIGHT AND WE 

498
00:21:50,224 --> 00:21:53,995
LOOKED AT THE SYSTEMIC TOXICITY 

499
00:21:53,995 --> 00:21:55,896
OF THIS PRODUCT AND WE FOUND 

500
00:21:55,896 --> 00:21:59,400
THAT THE PRODUCT WAS SAFE AND 

501
00:21:59,400 --> 00:22:06,774
THAT REMAIN FOR FOUR YEARS.  

502
00:22:06,774 --> 00:22:08,476
THAT IS A PRECLINICAL MODEL THAT

503
00:22:08,476 --> 00:22:13,080
WHEN WE INJECT THE CELLS THE 

504
00:22:13,080 --> 00:22:15,182
SHEEP WEIGHS ONE HUNDRED GRAMS 

505
00:22:15,182 --> 00:22:17,752
AND BY YEAR FOUR ONE HUNDRED 

506
00:22:17,752 --> 00:22:19,887
KILOS SO THE CELLS REMAIN AND 

507
00:22:19,887 --> 00:22:21,789
PRODUCE FACTOR EIGHT LEVELS WE 

508
00:22:21,789 --> 00:22:23,591
ALSO ASK THE QUESTION WHAT THIS 

509
00:22:23,591 --> 00:22:26,494
THERAPY WOULD BE SAFE FOR THE 

510
00:22:26,494 --> 00:22:27,962
MOTHER.  AND WE SHOW THAT 

511
00:22:27,962 --> 00:22:35,303
NEITHER THE CELLS OR THE PROTEIN

512
00:22:35,303 --> 00:22:36,937
PASS THE PLACENTAL BARRIER AND 

513
00:22:36,937 --> 00:22:39,307
REACH THE MOTHER.  WE WERE ABLE 

514
00:22:39,307 --> 00:22:41,776
TO HAVE THE CLINICAL TRIAL AFTER

515
00:22:41,776 --> 00:22:45,513
WE OBTAIN IND APPROVAL.  THE 

516
00:22:45,513 --> 00:22:46,647
SECOND QUESTION THAT WE WERE 

517
00:22:46,647 --> 00:22:49,283
ASKED WAS WHAT DO YOU SEE AS THE

518
00:22:49,283 --> 00:22:51,319
MOST PROMINENT SHARED OR 

519
00:22:51,319 --> 00:22:51,986
CROSSCUTTING CHALLENGES TO 

520
00:22:51,986 --> 00:22:54,755
GETTING THERAPIES TO PATIENTS?  

521
00:22:54,755 --> 00:22:59,760
AND WORKING IN A FIELD OF FETAL 

522
00:22:59,760 --> 00:23:01,295
THERAPIES, AND SPECIAL CELLULAR 

523
00:23:01,295 --> 00:23:03,764
THERAPIES WE KNOW THERE'S A NEED

524
00:23:03,764 --> 00:23:05,733
FOR AGE SPECIFIC THERAPEUTIC 

525
00:23:05,733 --> 00:23:07,568
PRODUCTS SUCH AS THE FETUS 

526
00:23:07,568 --> 00:23:09,437
DOESN'T HAVE THE SAME BIOLOGY AS

527
00:23:09,437 --> 00:23:12,840
AN ADULT OR EVEN CHILD.  WE ALSO

528
00:23:12,840 --> 00:23:15,376
NEED TO TREAT THESE PATIENTS 

529
00:23:15,376 --> 00:23:17,044
EARLY IN GESTATION AND 

530
00:23:17,044 --> 00:23:19,347
THEREFORE, WE NEED RELIABLE AND 

531
00:23:19,347 --> 00:23:22,016
NON EVASIVE DIAGNOSTIC PLATFORMS

532
00:23:22,016 --> 00:23:23,484
FOR EARLY DETECTION OF GENETIC 

533
00:23:23,484 --> 00:23:27,054
DISORDERS OR OTHER DISORDERS.  

534
00:23:27,054 --> 00:23:32,860
TO AND -- AND REPLACE THE 

535
00:23:32,860 --> 00:23:36,230
DIAGNOSTIC TOOLS BECAUSE TIME IS

536
00:23:36,230 --> 00:23:37,932
OF ESSENCE AND ALSO 

537
00:23:37,932 --> 00:23:38,999
EXTRAPOLATING TO A BROADER FIELD

538
00:23:38,999 --> 00:23:42,503
WE KNOW THAT THE TIME TO 

539
00:23:42,503 --> 00:23:46,474
MANUFACTURE PRODUCTS FOR 

540
00:23:46,474 --> 00:23:48,342
PERSONALIZED ALOE YES NAYIC IS 

541
00:23:48,342 --> 00:23:52,313
OF ESSENCE FOR THESE PATIENTS.  

542
00:23:52,313 --> 00:23:56,650
SO WE NEED A REDUCTION OF 

543
00:23:56,650 --> 00:23:59,754
PROCESSING AND HANDS ON TIME SO 

544
00:23:59,754 --> 00:24:03,057
SORT OF AUTOMATION THAT ABLE TO 

545
00:24:03,057 --> 00:24:04,258
GENERATE THESE PRODUCTS QUICKLY 

546
00:24:04,258 --> 00:24:06,394
WE NEED A CONSISTENCY OF RESULTS

547
00:24:06,394 --> 00:24:08,062
INDEPENDENT OF THE SITE OF 

548
00:24:08,062 --> 00:24:10,865
MANUFACTURING.  

549
00:24:10,865 --> 00:24:15,703
AND TO ADDRESS THE PRODUCTS IN 

550
00:24:15,703 --> 00:24:17,371
ORDER TO TRANSLATE THESE 

551
00:24:17,371 --> 00:24:19,373
PROJECTS QUICKLY TO THE CLINIC 

552
00:24:19,373 --> 00:24:22,443
WE NEED INFRASTRUCTURES TO 

553
00:24:22,443 --> 00:24:26,480
MANUFACTURE THESE PRODUCTS AT 

554
00:24:26,480 --> 00:24:29,049
ACADEMIC INSTITUTIONS WE NEED 

555
00:24:29,049 --> 00:24:30,151
INFRASTRUCTURES THAT WE CAN PUSH

556
00:24:30,151 --> 00:24:31,552
PRODUCTS THROUGH THE REGULATORY 

557
00:24:31,552 --> 00:24:35,523
APPROVAL OF NEW PRODUCTS.  AND 

558
00:24:35,523 --> 00:24:38,292
THOSE INSTITUTIONS TO PERFORM 

559
00:24:38,292 --> 00:24:39,994
CLINICAL TRIALS OR AT LEAST TO 

560
00:24:39,994 --> 00:24:42,797
ADMINISTER THE THERAPIES.  WE 

561
00:24:42,797 --> 00:24:47,368
ALSO NEED THE STANDARDIZED AND 

562
00:24:47,368 --> 00:24:52,840
VALIDATED SYSTEMS FOR CELL 

563
00:24:52,840 --> 00:24:54,875
ISOLATION AND WE NEED THE 

564
00:24:54,875 --> 00:24:55,976
RECRUITMENT WITH ACCURATE 

565
00:24:55,976 --> 00:24:58,479
INFORMATION AND FAIR ACCESS TO 

566
00:24:58,479 --> 00:24:59,246
DIAGNOSIS AND THERAPIES AND 

567
00:24:59,246 --> 00:25:01,582
LATELY, WHAT RESEARCH IS NEEDED 

568
00:25:01,582 --> 00:25:04,552
TO OVERCOME THESE CHALLENGES AND

569
00:25:04,552 --> 00:25:06,821
I THOUGHT THAT DEVELOPMENT -- A 

570
00:25:06,821 --> 00:25:08,556
VALUELATION OF DIAGNOSTIC 

571
00:25:08,556 --> 00:25:09,390
TECHNOLOGIES IS APPROPRIATE FOR 

572
00:25:09,390 --> 00:25:11,826
ALL AGES BECAUSE WE DON'T KNOW 

573
00:25:11,826 --> 00:25:13,027
THE INFLUENCE OF DISEASE STAGE 

574
00:25:13,027 --> 00:25:14,929
ON OUTCOME OF CELL THERAPIES. 

575
00:25:14,929 --> 00:25:17,898
WE NEED DEVELOPMENTAL CELL 

576
00:25:17,898 --> 00:25:19,967
THERAPIES SPECIFIC FOR PATIENT 

577
00:25:19,967 --> 00:25:21,502
AGE.  WE COULD USE MANUFACTURING

578
00:25:21,502 --> 00:25:23,370
CELL THERAPIES PLATFORMS THAT 

579
00:25:23,370 --> 00:25:28,576
COULD BE USED TO TREAT BROAD 

580
00:25:28,576 --> 00:25:30,411
RANGES OF DISEASES. 

581
00:25:30,411 --> 00:25:31,545
IDENTIFICATION AND MANUFACTURE 

582
00:25:31,545 --> 00:25:36,050
OF ALOE YES NAYIC SOURCES AND 

583
00:25:36,050 --> 00:25:38,452
LABEL CELL -- LABEL FREE CELL 

584
00:25:38,452 --> 00:25:40,221
SYSTEMS TO GENERATE AND REACH 

585
00:25:40,221 --> 00:25:43,090
POPULATIONS OF CELLS WITH 

586
00:25:43,090 --> 00:25:45,693
MINIMAL MANIPULATION.  THANK 

587
00:25:45,693 --> 00:25:54,702
YOU

588
00:25:54,702 --> 00:25:54,869
YOU.

589
00:25:54,869 --> 00:25:56,937
>> BOB CARTER: THAT WAS
PRETTY 

590
00:25:56,937 --> 00:25:59,473
WELL PERFECT.  ALAN IS ON DECK 

591
00:25:59,473 --> 00:26:01,075
AND DENNIS.  I WILL ADVANCE THE 

592
00:26:01,075 --> 00:26:02,676
SLIDES FOR YOU.  WE NEED TO 

593
00:26:02,676 --> 00:26:06,480
GET -- JANNA, HOW TO -- SO JUST 

594
00:26:06,480 --> 00:26:16,957
DOWN?  IS THAT YOU, DENNIS?

595
00:26:18,492 --> 00:26:19,026
>> DENNIS: (SPEAKER FAR
FROM 

596
00:26:19,026 --> 00:26:29,570
MIC) OF HOW WE CAN ADDRESS THESE

597
00:28:54,782 --> 00:29:05,259
CHALLENGES.  NEXT SLIDE.  OKAY, 

598
00:29:10,264 --> 00:29:11,665
SO WITH RESPECT TO CLONE TO 

599
00:29:11,665 --> 00:29:13,801
CLONE VARIATION AND THE CAPACITY

600
00:29:13,801 --> 00:29:14,935
TO DIFFERENTIATE INTO DIFFERENT 

601
00:29:14,935 --> 00:29:17,204
ADULT LANGUAGES I THINK IT'S KEY

602
00:29:17,204 --> 00:29:20,240
TO IDENTIFY EARLY MARKERS THAT 

603
00:29:20,240 --> 00:29:21,775
WOULD INDICATE THE CAPACITY OF A

604
00:29:21,775 --> 00:29:24,078
GIVEN CLONE TO DIFFERENTIATE 

605
00:29:24,078 --> 00:29:25,779
INTO THAT ADULT LINEAGE AND 

606
00:29:25,779 --> 00:29:28,215
THAT, AGAIN, IS KIND OF A 

607
00:29:28,215 --> 00:29:33,220
COMBINED BIOINFORMATICS CELL 

608
00:29:33,220 --> 00:29:38,992
BIOLOGY ISSUE.  WITH RESPECT TO 

609
00:29:38,992 --> 00:29:42,029
DIFFERENTIATING IPSC HAVE 

610
00:29:42,029 --> 00:29:44,098
DIFFERENT EFFICIENCIES AT LEAST 

611
00:29:44,098 --> 00:29:46,800
IN OUR CASE AND I THINK WE HAVE 

612
00:29:46,800 --> 00:29:49,603
A SPEAKER TOMORROW THE USE OF 

613
00:29:49,603 --> 00:29:52,339
ORGANOIDS WHERE YOU 

614
00:29:52,339 --> 00:29:54,575
DIFFERENTIATE IN A 3D MICRO 

615
00:29:54,575 --> 00:29:59,213
ENVIRONMENT WRA Y WHERE YOU HAV 

616
00:29:59,213 --> 00:30:01,148
CELL INTERACTION TO SOLVE THAT 

617
00:30:01,148 --> 00:30:01,415
PROBLEM. 

618
00:30:01,415 --> 00:30:03,951
WITH RESPECT TO TO USING 

619
00:30:03,951 --> 00:30:04,852
ORGANOIDS, AGAIN, I THINK 

620
00:30:04,852 --> 00:30:07,621
IT'S -- IT'LL BE CURIOUS TO SEE 

621
00:30:07,621 --> 00:30:12,760
HOW THE FDA RESPONDS TO USING 

622
00:30:12,760 --> 00:30:16,263
ORGANOIDS THAT MAY ACTUALLY -- 

623
00:30:16,263 --> 00:30:18,198
GRAPHED IN AN HOUR PRECLINICAL 

624
00:30:18,198 --> 00:30:21,435
TEST FUNCTIONAL BUT WE MAY NOT 

625
00:30:21,435 --> 00:30:24,471
IDENTIFY ALL THE CELL TYPES TO 

626
00:30:24,471 --> 00:30:28,008
THE DEGREE OF CHARACTERIZATION 

627
00:30:28,008 --> 00:30:30,978
THAT THE FDA MAY REQUIRE WITH 

628
00:30:30,978 --> 00:30:31,612
RESPECT TO IDENTIFYING HEALTH 

629
00:30:31,612 --> 00:30:33,680
TARGET INSTEAD OF REQUIRING 

630
00:30:33,680 --> 00:30:34,648
SEQUENCING WHICH IS CLEARLY 

631
00:30:34,648 --> 00:30:36,984
GOING TO SHOW A LOT OF MUTATIONS

632
00:30:36,984 --> 00:30:39,386
THAT MAY NOT HAVE ACTUALLY AN 

633
00:30:39,386 --> 00:30:45,058
IMPACT ON FUNCTION, MAYBE SELECT

634
00:30:45,058 --> 00:30:45,626
PANEL THAT WOULD POTENTIAL 

635
00:30:45,626 --> 00:30:48,529
ONCOGENES TO FOCUS ON AND 

636
00:30:48,529 --> 00:30:50,731
FINALLY WITH REQUIRE POLY 

637
00:30:50,731 --> 00:30:54,168
ALLYLIC DISEASES, INSTEAD OF ONE

638
00:30:54,168 --> 00:30:58,772
GUIDE PER IND CONSIDER EACH 

639
00:30:58,772 --> 00:31:02,643
GUIDE RNA HAS AN AGENT CHANGE 

640
00:31:02,643 --> 00:31:03,944
AND I THINK THIS WOULD SIMPLIFY 

641
00:31:03,944 --> 00:31:06,613
THIS ISSUE FOR THOSE WORKING ON 

642
00:31:06,613 --> 00:31:09,683
RARE DISEASES THAT ARE POLY 

643
00:31:09,683 --> 00:31:10,217
ALLELIC.  SO THOSE ARE MY 

644
00:31:10,217 --> 00:31:17,958
COMMENTS.

645
00:31:17,958 --> 00:31:21,228
>> THANK YOU, DENNIS, ALAN
WITH 

646
00:31:21,228 --> 00:31:27,167
TIMOTHY CAMP ON DECK.  IS 

647
00:31:27,167 --> 00:31:36,643
TIMOTHY HERE, YEP.

648
00:31:36,643 --> 00:31:41,982
>> I GOT MY RPIP AWARD IN
2020. 

649
00:31:41,982 --> 00:31:43,350
THERE WAS A LOT OF WORK THAT WAS

650
00:31:43,350 --> 00:31:47,154
NOT FUNDED BUT PART OF TWO 

651
00:31:47,154 --> 00:31:49,456
COMPANIES I'VE WORKED WITH.  THE

652
00:31:49,456 --> 00:31:53,026
GOAL OF OUR WORK WAS TO BRING AN

653
00:31:53,026 --> 00:31:56,563
OFF THE SHELF ALOE YES NAYIC 

654
00:31:56,563 --> 00:31:59,933
DERIVED CELL TO THE MARKET.  TO 

655
00:31:59,933 --> 00:32:03,170
TREAT AGE-RELATED MACULAR 

656
00:32:03,170 --> 00:32:04,238
DEGENERATION DISEASE THAT 

657
00:32:04,238 --> 00:32:05,973
AFFECTS NEARLY TWO HUNDRED 

658
00:32:05,973 --> 00:32:08,408
MILLION PEOPLE WORLDWIDE THE 

659
00:32:08,408 --> 00:32:09,776
PICTURES ARE EXAMPLES OF THAT 

660
00:32:09,776 --> 00:32:12,880
PRODUCT BUT THE RMIP AWARD WAS 

661
00:32:12,880 --> 00:32:14,348
FOR THE DEVELOPMENT OF MASTER 

662
00:32:14,348 --> 00:32:17,951
AND WORKING BANKS FOR USE IN 

663
00:32:17,951 --> 00:32:19,453
THIS ALOE YES NAYIC CELL THERAPY

664
00:32:19,453 --> 00:32:22,022
AND MAYBE OTHERS.  WHEN WE DID 

665
00:32:22,022 --> 00:32:24,258
THAT WORK, THE CELL LINE THAT WE

666
00:32:24,258 --> 00:32:26,226
WERE WORKING WITH WHICH WAS A 

667
00:32:26,226 --> 00:32:29,229
RARE CELL LINE BUT WE HAVE FOUND

668
00:32:29,229 --> 00:32:34,268
WITH RIPCSS IS IT'S 5% OF LINES 

669
00:32:34,268 --> 00:32:36,737
THAT WE'VE TESTED HAVE THE 

670
00:32:36,737 --> 00:32:37,337
CHARACTERISTICS THAT WE WERE 

671
00:32:37,337 --> 00:32:41,208
LOOKING FOR IN AN ALOE YES NAYIC

672
00:32:41,208 --> 00:32:42,743
THERAPY WITH REGARD TO 

673
00:32:42,743 --> 00:32:44,378
DIFFERENTIATION AND WITH FIVE 

674
00:32:44,378 --> 00:32:46,246
MINUTES I CAN'T GO INTO DETAILS 

675
00:32:46,246 --> 00:32:49,583
OF THAT.  BUT ABOUT 95% DON'T SO

676
00:32:49,583 --> 00:32:50,484
THIS WAS A VERY SPECIAL CELL 

677
00:32:50,484 --> 00:32:52,319
LINE WE DID THE MASTER BANK WE 

678
00:32:52,319 --> 00:32:53,854
DID THE WORKING BANK.  WE HAD 

679
00:32:53,854 --> 00:32:56,957
ALL OF THE DOCUMENTATION AND 

680
00:32:56,957 --> 00:32:58,926
REGULATORY FILINGS REVIEWED 

681
00:32:58,926 --> 00:33:00,594
ACTUALLY BY THREE DIFFERENT 

682
00:33:00,594 --> 00:33:02,195
INDEPENDENT CONSULTANTS AND 

683
00:33:02,195 --> 00:33:04,064
DETERMINED AFTER THAT AN 

684
00:33:04,064 --> 00:33:04,698
INTERACTION THAT THERE WERE A 

685
00:33:04,698 --> 00:33:06,366
FEW PROBLEMS WITH THAT CELL LINE

686
00:33:06,366 --> 00:33:08,101
AND THESE WERE NOT IN THE AREA 

687
00:33:08,101 --> 00:33:10,704
OF DONOR ELIGIBILITY, 

688
00:33:10,704 --> 00:33:12,940
DOCUMENTATION SURROUNDING THE 

689
00:33:12,940 --> 00:33:13,840
PROGRAMMING VECTORS AND 

690
00:33:13,840 --> 00:33:15,509
UNFORTUNATELY SOME POOR 

691
00:33:15,509 --> 00:33:22,482
RECORDKEEPING AROUND THE FIE  

692
00:33:22,482 --> 00:33:24,551
FIBROBLASTS EXTENSION. 

693
00:33:24,551 --> 00:33:25,986
IN THE SUBSEQUENT YEARS WE MADE 

694
00:33:25,986 --> 00:33:29,423
SOME NEW CELL LINES OUR DONOR 

695
00:33:29,423 --> 00:33:31,058
ELIGIBILITY CRITERIA FOR REVISED

696
00:33:31,058 --> 00:33:32,826
AND THE COMPLIANT PROCESSES THAT

697
00:33:32,826 --> 00:33:34,962
COVER THE POOR RECORDKEEPING 

698
00:33:34,962 --> 00:33:36,930
WERE PUT INTO PLACE.  AND A NEW 

699
00:33:36,930 --> 00:33:41,201
CELL LINE WAS GENERATED USING 

700
00:33:41,201 --> 00:33:43,670
GMP-LIKE PRACTICES AND I WANT TO

701
00:33:43,670 --> 00:33:45,539
SAY GMP-LIKE BECAUSE WE'RE 

702
00:33:45,539 --> 00:33:46,873
MAKING THIS LINE ONE TIME AND 

703
00:33:46,873 --> 00:33:48,675
IT'S ALWAYS BEEN AN ISSUE 

704
00:33:48,675 --> 00:33:50,610
BECAUSE WHAT I HAVE FOUND WITH 

705
00:33:50,610 --> 00:33:52,879
IPCSS IS ONE IPCS DOES NOT WORK 

706
00:33:52,879 --> 00:33:55,048
THE SAME AS THE NEXT THE NUMBER 

707
00:33:55,048 --> 00:33:56,917
OF DEVIATIONS THAT YOU HAVE TO 

708
00:33:56,917 --> 00:33:58,085
FILE IN YOUR RECORDKEEPING IF 

709
00:33:58,085 --> 00:34:01,388
YOU THINK THAT EVERY IPSC 

710
00:34:01,388 --> 00:34:03,457
MANUFACTURE THE SAME WAY IS 

711
00:34:03,457 --> 00:34:07,094
GOING TO BE DONE THE SAME WAY IS

712
00:34:07,094 --> 00:34:09,029
INCALCULABLE GMP-LIKE AND FROM 

713
00:34:09,029 --> 00:34:12,265
THIS, WE HAD ONE LINE OUT OF 23 

714
00:34:12,265 --> 00:34:14,634
CLONES THAT WERE ISOLATED FROM 

715
00:34:14,634 --> 00:34:17,170
FIBROBLASTS THAT WERE DONATED BY

716
00:34:17,170 --> 00:34:19,740
FOUR SEPARATE DONORS THAT HAD 

717
00:34:19,740 --> 00:34:21,208
SUITABLE PROPERTIES FOR 

718
00:34:21,208 --> 00:34:24,277
DEVELOPMENT AND TO PUSH FORWARD 

719
00:34:24,277 --> 00:34:26,480
IN OUR WORK.  SO WHAT ARE THE 

720
00:34:26,480 --> 00:34:27,681
CHALLENGES THAT WE IDENTIFIED 

721
00:34:27,681 --> 00:34:29,349
HERE?  I LISTED TWO BECAUSE 

722
00:34:29,349 --> 00:34:30,917
THESE ARE THE TWO BIG ONES IN MY

723
00:34:30,917 --> 00:34:32,386
OPINION THE FIRST ONE REALLY IS 

724
00:34:32,386 --> 00:34:36,456
THE MANUFACTURER OF IPSCS IN OUR

725
00:34:36,456 --> 00:34:37,791
OPINION YOU NEED TO HAVE BETTER 

726
00:34:37,791 --> 00:34:41,595
THAN A 98% YIELD OF THE FINAL 

727
00:34:41,595 --> 00:34:43,430
DESIRED CELL TYPE AND PREFERABLY

728
00:34:43,430 --> 00:34:44,865
HIGHER THAN THAT THOUGH IT'S 

729
00:34:44,865 --> 00:34:46,166
DIFFICULT TO ASSESS PERCENTAGES 

730
00:34:46,166 --> 00:34:48,502
THAT ARE GETTING INTO THAT RANGE

731
00:34:48,502 --> 00:34:50,370
I KNOW IN OUR INTERACTIONS WITH 

732
00:34:50,370 --> 00:34:53,340
THE AGENCY THEY'VE ASKED US 

733
00:34:53,340 --> 00:34:54,508
EVERY SINGLE TIME TO TELL THEM 

734
00:34:54,508 --> 00:34:57,077
WHAT THE IMPURITIES ARE.  SO 

735
00:34:57,077 --> 00:34:58,011
THIS IS SOMETHING THAT WE 

736
00:34:58,011 --> 00:35:00,680
DEFINITELY SEE AS A CHALLENGE.  

737
00:35:00,680 --> 00:35:02,449
ONE OF THE PROBLEMS IN 

738
00:35:02,449 --> 00:35:04,918
GENERATING THE IPS LINES IS THAT

739
00:35:04,918 --> 00:35:08,288
THE EXPRESSION OF POTENT MARKERS

740
00:35:08,288 --> 00:35:09,523
OR DIFFERENTIATION REALLY 

741
00:35:09,523 --> 00:35:10,891
DOESN'T CORRELATE WITH THE 

742
00:35:10,891 --> 00:35:12,325
UTILITY OF THE LINE AT ALL.  

743
00:35:12,325 --> 00:35:14,027
EVERY SINGLE ONE OF THOSE 23 

744
00:35:14,027 --> 00:35:15,529
CLONES THAT I MENTIONED IN THE 

745
00:35:15,529 --> 00:35:17,764
PREVIOUS SLIDE ALL OF THEM 

746
00:35:17,764 --> 00:35:20,233
EXPRESSED LARGE PERCENTAGES OF 

747
00:35:20,233 --> 00:35:22,402
POTENCY MARKERS, ON FLOW, ALL OF

748
00:35:22,402 --> 00:35:25,572
THEM PERFORMED BEAUTIFULLY IN 

749
00:35:25,572 --> 00:35:28,175
TRILINEAGE ASSAYS AND THE VAST 

750
00:35:28,175 --> 00:35:29,142
MAJORITY OF THEM WERE ABSOLUTELY

751
00:35:29,142 --> 00:35:32,412
GARBAGE FOR USE IN TERMS OF 

752
00:35:32,412 --> 00:35:34,714
MANUFACTURE OF A THERAPEUTIC THE

753
00:35:34,714 --> 00:35:37,784
IPS LINES THAT YOU DO HAVE TO 

754
00:35:37,784 --> 00:35:39,119
HAVE NO SPONTANEOUS 

755
00:35:39,119 --> 00:35:40,320
DIFFERENTIATION.  THIS IS ONE OF

756
00:35:40,320 --> 00:35:41,788
THE ATTRIBUTES THAT WE LOOKED AT

757
00:35:41,788 --> 00:35:44,224
AND SOMETHING THAT NEEDS TO BE 

758
00:35:44,224 --> 00:35:45,459
LOOKED INTO TO UNDERSTAND HOW 

759
00:35:45,459 --> 00:35:47,594
AND WHY WE CAN REMOVE THAT.  THE

760
00:35:47,594 --> 00:35:49,663
OTHER THINGS THESE ARE JUST 

761
00:35:49,663 --> 00:35:51,298
REGULATORY CONCERNS REALLY THAT 

762
00:35:51,298 --> 00:35:53,500
PURIFICATION INVOLVING REAGENTS 

763
00:35:53,500 --> 00:35:54,801
SO WHEN YOU'RE DIFFERENTIATING 

764
00:35:54,801 --> 00:35:58,038
THAT MAY BE REGULATED AS 

765
00:35:58,038 --> 00:35:59,106
BIOLOGICS ON THEIR OWN WHICH 

766
00:35:59,106 --> 00:36:01,108
REALLY MAKES THE REGULATORY 

767
00:36:01,108 --> 00:36:02,476
FILINGS EXTRAORDINARILY 

768
00:36:02,476 --> 00:36:04,878
COMPLICATED JUST A PERSONAL 

769
00:36:04,878 --> 00:36:06,480
EXPERIENCE CDMOS DO NOT 

770
00:36:06,480 --> 00:36:07,914
APPRECIATE THE CHALLENGES OF 

771
00:36:07,914 --> 00:36:10,484
WORKING WITH IPSCS AND REALLY 

772
00:36:10,484 --> 00:36:13,053
ULTIMATELY, IF YOU WANT TO BRING

773
00:36:13,053 --> 00:36:16,523
AN ALOE YES NAYIC CELL TO MARKET

774
00:36:16,523 --> 00:36:19,726
YOU NEED TO HAVE UNIVERSAL DONOR

775
00:36:19,726 --> 00:36:22,729
CELLS THE COMPLEXITY IS SUCH TO 

776
00:36:22,729 --> 00:36:24,131
TAKE ONE THAT IS GOOD AND 

777
00:36:24,131 --> 00:36:25,999
FURTHER SUBJECT IT TO ANY SORT 

778
00:36:25,999 --> 00:36:30,737
OF GENE EDDIITING OR OTHER 

779
00:36:30,737 --> 00:36:31,872
PROCEDURES LIKE THAT MAY HAVE 

780
00:36:31,872 --> 00:36:33,707
TERRIBLE CONSEQUENCES FOR THE 

781
00:36:33,707 --> 00:36:35,275
UTILITY OF THAT CELL LINE I WILL

782
00:36:35,275 --> 00:36:44,184
LEAVE IT AT THAT.  THANK YOU.

783
00:36:44,184 --> 00:36:48,555
>> TIM CAMP AND THEN FINN
WILL 

784
00:36:48,555 --> 00:36:51,491
BE VIRTUAL AFTER TIM.

785
00:36:51,491 --> 00:36:53,326
>> OKAY.  THANK YOU VERY
MUCH 

786
00:36:53,326 --> 00:36:55,228
FOR THE INVITATION AND IT'S MY 

787
00:36:55,228 --> 00:37:00,834
PLEASURE TO SHARE SOME OF THE 

788
00:37:00,834 --> 00:37:03,336
WORK THAT WE PERFORMED WITH MY 

789
00:37:03,336 --> 00:37:05,539
CO-PI WE DID A PROJECT LOOKING 

790
00:37:05,539 --> 00:37:10,410
AT CARDIAC CELLS IN A MYOCARDIAL

791
00:37:10,410 --> 00:37:15,849
INFARCTION MODEL WE TEAMED WITH 

792
00:37:15,849 --> 00:37:17,984
FUJIFILM THAT MADE IPS DERIVED 

793
00:37:17,984 --> 00:37:20,520
CELLS.  AND WE COMBINED THAT 

794
00:37:20,520 --> 00:37:24,858
WITH CARDIAC EXTRACELLULAR 

795
00:37:24,858 --> 00:37:28,428
MATRIX MADE FROM DENSE 

796
00:37:28,428 --> 00:37:30,230
FIBROBLASTS, CARDIAC FIBROBLASTS

797
00:37:30,230 --> 00:37:31,498
CULTURES AND THEN MANUFACTURED. 

798
00:37:31,498 --> 00:37:36,469
THE IDEA IF WE TRANSPLANTED THE 

799
00:37:36,469 --> 00:37:40,140
CELLS IN A MATRIX FOLLOWING A 

800
00:37:40,140 --> 00:37:43,843
MODEL PRODUCED BY BALLOON 

801
00:37:43,843 --> 00:37:46,246
OCCLUSION AND REPERFUSION AND A 

802
00:37:46,246 --> 00:37:48,048
MONTH LATER DELIVER THE CELLS BY

803
00:37:48,048 --> 00:37:52,085
DELIVERY USING A CATHETER BASED 

804
00:37:52,085 --> 00:37:57,557
SYSTEM BY THE DOCTOR AND MAPPING

805
00:37:57,557 --> 00:37:59,659
TO SEE IF WE CAN REGENERATE 

806
00:37:59,659 --> 00:38:02,262
CARDIAC MUSCLE AND LOOK AT 

807
00:38:02,262 --> 00:38:04,364
THINGS LIKE ARRHYTHMIA RISK WITH

808
00:38:04,364 --> 00:38:06,666
A LOOP RECORDER, CARDIAC 

809
00:38:06,666 --> 00:38:09,336
FUNCTION WITH MRI ANALYSIS AND 

810
00:38:09,336 --> 00:38:11,037
PRESSURE VOLUME LOOP ANALYSIS 

811
00:38:11,037 --> 00:38:13,106
AND THEN TERMINAL STUDIES 

812
00:38:13,106 --> 00:38:15,609
LOOKING AT THE HISTOLOGIC IMPACT

813
00:38:15,609 --> 00:38:19,279
ON THE HEART TO GET CLOSER TO 

814
00:38:19,279 --> 00:38:20,313
CLINICAL APPLICATIONS BUT THIS 

815
00:38:20,313 --> 00:38:23,149
IS PRECLINICAL.  AND WHAT WE 

816
00:38:23,149 --> 00:38:24,117
ACCOMPLISHED IN THIS STUDY WHICH

817
00:38:24,117 --> 00:38:26,486
DOING A LARGE ANIMAL STUDY IN 

818
00:38:26,486 --> 00:38:28,521
THIS WAY WITH THESE UNIQUE 

819
00:38:28,521 --> 00:38:29,956
PRODUCTS, WAS UNIQUELY ENABLED 

820
00:38:29,956 --> 00:38:35,662
BY THE RMIP WE DID SHOW THAT THE

821
00:38:35,662 --> 00:38:38,064
CCPS COULD ENGRAFT AND COULD 

822
00:38:38,064 --> 00:38:40,634
DIFFERENTIATE IN THE INFARCTED 

823
00:38:40,634 --> 00:38:43,103
HEART THIS IS IMAGES FROM TWO 

824
00:38:43,103 --> 00:38:44,604
WEAK HEARTS IF YOU HAVE GOOD 

825
00:38:44,604 --> 00:38:46,106
EYES THE LITTLE RED DOTS THERE 

826
00:38:46,106 --> 00:38:48,174
ARE THE HUMAN CELLS SO THEY'RE 

827
00:38:48,174 --> 00:38:51,478
BEGINNING TO FORM EARLY STAGE 

828
00:38:51,478 --> 00:38:53,980
CARDIOMYOCYTES THAT FURTHER 

829
00:38:53,980 --> 00:38:56,950
MATURE IN TIME AND WE SAW SOME 

830
00:38:56,950 --> 00:38:57,617
IMPACT ON RESERVE IN OTHER WORDS

831
00:38:57,617 --> 00:38:59,819
THE HEART PERFORMED BETTER IN 

832
00:38:59,819 --> 00:39:02,756
RESPONSE TO BETA ADRA NEVER JUST

833
00:39:02,756 --> 00:39:04,291
IN CASE STIMULATION AFTER 

834
00:39:04,291 --> 00:39:06,126
RECEIVING THE CELLS. 

835
00:39:06,126 --> 00:39:08,628
HOWEVER, OUR PRIMARY END POINT 

836
00:39:08,628 --> 00:39:12,365
CARDIAC MRI EJECTION FRACTION 

837
00:39:12,365 --> 00:39:13,633
DID NOT SHOW A SIGNIFICANT 

838
00:39:13,633 --> 00:39:15,435
DIFFERENCE SO WE DID RUN INTO 

839
00:39:15,435 --> 00:39:17,504
SOME CHALLENGES.  AND I'LL 

840
00:39:17,504 --> 00:39:18,338
HIGHLIGHT CHALLENGES 

841
00:39:18,338 --> 00:39:22,342
PARTICULARLY FOCUSING ON HUMAN 

842
00:39:22,342 --> 00:39:23,977
POTENT STEM CELL THERAPIES AND 

843
00:39:23,977 --> 00:39:25,679
SOME OF THE CROSSCUTTING 

844
00:39:25,679 --> 00:39:27,147
CHALLENGES THAT WE SEE ARE THAT 

845
00:39:27,147 --> 00:39:30,183
OFF THE SHELF ALOE YES NAYIC 

846
00:39:30,183 --> 00:39:31,117
THERAPIES REALLY WE NEED TO 

847
00:39:31,117 --> 00:39:32,686
THINK ABOUT IMMUNE TOLERANCE AND

848
00:39:32,686 --> 00:39:34,954
HOW BEST TO PERFORM IMMUNE 

849
00:39:34,954 --> 00:39:36,690
SUPPRESSION AS NEEDED AND THAT 

850
00:39:36,690 --> 00:39:39,626
IS I THINK A VERY MUCH SHARED 

851
00:39:39,626 --> 00:39:41,695
CHALLENGE ACROSS VARIOUS 

852
00:39:41,695 --> 00:39:42,495
APPROACHES.  ALTERNATIVELY, IF 

853
00:39:42,495 --> 00:39:44,964
WE'RE THINKING ABOUT 

854
00:39:44,964 --> 00:39:48,702
PERSONALIZED OR ONTOLOGIST 

855
00:39:48,702 --> 00:39:51,838
THERAPIES BEING ABLE TO IN A 

856
00:39:51,838 --> 00:39:54,708
TIME EFFICIENT MANNER CELLS IS 

857
00:39:54,708 --> 00:39:55,775
CLEARLY A CHALLENGE.  BUT 

858
00:39:55,775 --> 00:39:57,210
PERHAPS THE BIGGEST CHALLENGE WE

859
00:39:57,210 --> 00:39:59,045
FACED IN OUR PROJECT WAS THAT WE

860
00:39:59,045 --> 00:40:02,115
NEEDED PROFOUND 

861
00:40:02,115 --> 00:40:04,718
IMMUNOSUPPRESSION FOR THE ZENO 

862
00:40:04,718 --> 00:40:06,486
YES NAYIC PRODUCT EVALUATION IN 

863
00:40:06,486 --> 00:40:10,457
THE SWINE MODEL AND WE SAW 

864
00:40:10,457 --> 00:40:12,192
PROBLEMS WITH OPPORTUNISTIC 

865
00:40:12,192 --> 00:40:14,461
INFECTIONS AND ALSO WE WORRY 

866
00:40:14,461 --> 00:40:15,695
THAT HAD THE IMMUNOSUPPRESSION 

867
00:40:15,695 --> 00:40:17,664
WAS ALTERING THE PATH OF 

868
00:40:17,664 --> 00:40:19,933
PHYSIOLOGY BECAUSE FOLLOWING THE

869
00:40:19,933 --> 00:40:21,034
INFARCTION THE IMMUNE SYSTEM 

870
00:40:21,034 --> 00:40:24,604
CONTINUES TO PLAY A PROMINENT 

871
00:40:24,604 --> 00:40:25,238
ROLE IN THE CARDIAC REMODELLING.

872
00:40:25,238 --> 00:40:32,412
TO GIVE YOU AN IDEA THE IMMUNE 

873
00:40:32,412 --> 00:40:33,947
SUPPRESSION REQUIRED CYCLOSPORIN

874
00:40:33,947 --> 00:40:37,183
AND ALSO AN IMMUNO MODULATOR 

875
00:40:37,183 --> 00:40:39,285
THAT BLOCKS T-CELL FUNCTION AND 

876
00:40:39,285 --> 00:40:42,689
THIS PROFOUND IMMUNOSUPPRESSION 

877
00:40:42,689 --> 00:40:44,891
CAUSED US TO HAVE A NUMBER OF 

878
00:40:44,891 --> 00:40:47,160
ANIMALS THAT GOT OPPORTUNISTIC 

879
00:40:47,160 --> 00:40:50,163
INFECTIONS INSTEAD OF -- IN 

880
00:40:50,163 --> 00:40:55,869
SPITE OF PROPHYLACTIC 

881
00:40:55,869 --> 00:40:57,604
ANTIBIOTICS.  SO HOW CAN WE 

882
00:40:57,604 --> 00:40:58,605
OVERCOME SOME OF THESE 

883
00:40:58,605 --> 00:41:00,140
CHALLENGES? WELL FOR THE ISSUE 

884
00:41:00,140 --> 00:41:03,443
OF IMMUNE TOLERANCE OBVIOUSLY 

885
00:41:03,443 --> 00:41:05,712
MANY GROUPS ARE LOOKING AT GENE 

886
00:41:05,712 --> 00:41:07,680
EDITING APPROACHES KNOCKING OUT 

887
00:41:07,680 --> 00:41:09,449
A VARIETY OF MOLECULES AS WELL 

888
00:41:09,449 --> 00:41:11,251
AS OVEREXPRESSING SOME.  I THINK

889
00:41:11,251 --> 00:41:13,420
IT'S GOING TO TAKE US TIME TO 

890
00:41:13,420 --> 00:41:17,157
UNDERSTAND WHAT THE APPROPRIATE 

891
00:41:17,157 --> 00:41:18,825
HYPO IMMUNE CELLS ARE AND WE 

892
00:41:18,825 --> 00:41:22,829
NEED GOOD STUDIES FOR THAT.  FOR

893
00:41:22,829 --> 00:41:25,899
AUTOLOGOUS APPROACHES, OBVIOUSLY

894
00:41:25,899 --> 00:41:27,600
QUALITY CONTROL PRACTICES AND 

895
00:41:27,600 --> 00:41:28,902
PROCESSES NEED TO IMPROVE BUT 

896
00:41:28,902 --> 00:41:30,770
THE THING AGAIN I WILL HIGHLIGHT

897
00:41:30,770 --> 00:41:33,773
IS WE REALLY NEED PREDICTIVE 

898
00:41:33,773 --> 00:41:35,708
AFFORDABLE ANIMAL MODELS THAT 

899
00:41:35,708 --> 00:41:38,445
DON'T REQUIRE SUCH MARKED IMMUNO

900
00:41:38,445 --> 00:41:41,247
SIP PRESENTATION FOR THESE ZENO 

901
00:41:41,247 --> 00:41:42,515
YES NAYIC PRODUCTS. 

902
00:41:42,515 --> 00:41:44,150
JUST TO GIVE YOU AN EXAMPLE OF 

903
00:41:44,150 --> 00:41:48,221
WHY I SAID AFFORDABLE THIS WAS 

904
00:41:48,221 --> 00:41:49,789
TWO THOUSAND DOLLARS PER DOSE 

905
00:41:49,789 --> 00:41:52,158
REQUIRING DOSES EVERY TWO WEEKS,

906
00:41:52,158 --> 00:41:54,494
THE COST OF DRUGS AND THE 

907
00:41:54,494 --> 00:41:55,462
NECESSARY MAINTENANCE OF THIS 

908
00:41:55,462 --> 00:41:57,464
MODEL ARE EXTRAORDINARY SO IF WE

909
00:41:57,464 --> 00:41:59,632
CAN GET HUMANIZED MODELS WE 

910
00:41:59,632 --> 00:42:01,100
ALREADY HAVE GOOD PROGRESS WITH 

911
00:42:01,100 --> 00:42:05,004
MOUSE MODELS BUT WE REALLY NEED 

912
00:42:05,004 --> 00:42:07,307
LARGER MAMMALS THAT WOULD BE A 

913
00:42:07,307 --> 00:42:08,741
MAJOR ADVANCE AND CORE 

914
00:42:08,741 --> 00:42:09,809
FACILITIES THAT REALLY ARE 

915
00:42:09,809 --> 00:42:12,645
EXPERT AT THESE UNIQUE ANIMAL 

916
00:42:12,645 --> 00:42:23,189
MODELS WOULD ALSO HELP.  THANKS.

917
00:42:32,799 --> 00:42:34,968
>> JANNA, HOW DO WE DO
THIS?

918
00:42:34,968 --> 00:42:38,905
>> GOOD MORNING, CAN YOU
HEAR ME

919
00:42:38,905 --> 00:42:40,874
OKAY?

920
00:42:40,874 --> 00:42:43,610
>> AND YING IF YOU COULD
BE ON 

921
00:42:43,610 --> 00:42:43,943
DECK, PLEASE.

922
00:42:43,943 --> 00:42:46,279
>> SINCERE APOLOGIES THEY
CANNOT

923
00:42:46,279 --> 00:42:47,447
BE THERE IN-PERSON I'M GIVING 

924
00:42:47,447 --> 00:42:51,417
THE UPDATE FOR BOSTON UNIVERSITY

925
00:42:51,417 --> 00:42:52,886
RMIP GROUP LED BY DARRYL AND I 

926
00:42:52,886 --> 00:42:59,726
WAS A CO-PI ON THESE DUD  

927
00:42:59,726 --> 00:42:59,993
STUDIES. 

928
00:42:59,993 --> 00:43:02,061
OUR GOAL IS LUNG REGENERATION.  

929
00:43:02,061 --> 00:43:04,163
AND OUR VISION IS THAT IN THE 

930
00:43:04,163 --> 00:43:05,698
RELATIVE SHORTER TERM GENETIC 

931
00:43:05,698 --> 00:43:08,268
DISEASES OF THE AIRWAY LIKE 

932
00:43:08,268 --> 00:43:10,470
CYSTIC FIBROSIS COULD IN THEORY 

933
00:43:10,470 --> 00:43:12,405
BE CURED BY CELL BASED THERAPY 

934
00:43:12,405 --> 00:43:15,808
TO THE AIRWAYS.  AND I'M JUST 

935
00:43:15,808 --> 00:43:19,112
GOING TO SHOW YOU THIS ONE DATA 

936
00:43:19,112 --> 00:43:21,114
SLIDE WHICH I THINK WAS A 

937
00:43:21,114 --> 00:43:22,749
CRUCIAL TO US.  AND ACHIEVED 

938
00:43:22,749 --> 00:43:26,653
THROUGH THE RMIP FUNDING AND 

939
00:43:26,653 --> 00:43:28,321
THIS IS THE MOST IMPORTANT DATA 

940
00:43:28,321 --> 00:43:32,625
SLIDE I'VE SEEN SO FAR IN MY 

941
00:43:32,625 --> 00:43:37,096
CAREER SO IPSC DERIVED BASAL 

942
00:43:37,096 --> 00:43:37,864
CELLS FROM A MOUSE THAT WERE 

943
00:43:37,864 --> 00:43:41,501
DELIVERED TO A TRACHEA AFTER A 

944
00:43:41,501 --> 00:43:42,335
DETERGENT BASED INJURY AND THIS 

945
00:43:42,335 --> 00:43:45,605
IS TWO YEARS LATER AND THIS IS A

946
00:43:45,605 --> 00:43:49,242
WHOLE TRACHEAL.  SO VERY LOW 

947
00:43:49,242 --> 00:43:51,878
MAGNIFICATION VIEW AND YOU CAN 

948
00:43:51,878 --> 00:43:54,180
SEE HIGHLY EFFICIENT GRAFTED 

949
00:43:54,180 --> 00:43:55,448
CELLS THAT IS CLEARLY DURABLE 

950
00:43:55,448 --> 00:43:57,951
BECAUSE THIS IS AFTER TWO YEARS 

951
00:43:57,951 --> 00:44:02,088
AND THESE CELLS -- THE DELIVERED

952
00:44:02,088 --> 00:44:05,625
CELLS WERE AN AIRWAY CELL CALLED

953
00:44:05,625 --> 00:44:07,794
THE BASAL CELL SO ESSENTIALLY WE

954
00:44:07,794 --> 00:44:10,096
WERE ABLE TO SHOW THAT DELIVERY 

955
00:44:10,096 --> 00:44:12,899
OF THIS CELL WAS ABLE TO 

956
00:44:12,899 --> 00:44:14,601
RECONSTITUTE ALL THE AIRWAY 

957
00:44:14,601 --> 00:44:15,635
EPITHELIUM FOR THE LIFETIME OF 

958
00:44:15,635 --> 00:44:17,070
THE MOUSE AND WE WERE ABLE TO 

959
00:44:17,070 --> 00:44:21,641
REPEAT THIS WITH A HUMAN IPSC 

960
00:44:21,641 --> 00:44:24,043
DERIVED BASAL CELLS.  AND WE 

961
00:44:24,043 --> 00:44:27,614
ALSO HAVE DATA JUST PUBLISHED IN

962
00:44:27,614 --> 00:44:29,916
THE COMPARTMENT SO THESE PAPERS 

963
00:44:29,916 --> 00:44:33,920
JUST CAME OUT BACK-TO-BACK IN 

964
00:44:33,920 --> 00:44:34,854
CELL STEM CELL WE ARE REALLY 

965
00:44:34,854 --> 00:44:37,090
EXCITED ABOUT THIS WE THINK, FOR

966
00:44:37,090 --> 00:44:39,425
EXAMPLE, YOU KNOW, CYSTIC 

967
00:44:39,425 --> 00:44:42,295
FIBROSIS JUST TO GIVE YOU AN 

968
00:44:42,295 --> 00:44:45,398
IDEA THERE'S HIGHLY EFFECTIVE 

969
00:44:45,398 --> 00:44:46,332
TREATMENTS.  THAT'S A LIFELONG 

970
00:44:46,332 --> 00:44:48,368
THERAPY THAT CURRENTLY COSTS 

971
00:44:48,368 --> 00:44:52,739
300,000 DOLLARS PER YEAR.  SO IN

972
00:44:52,739 --> 00:44:54,440
THINKING ABOUT NEXT STEPS WE 

973
00:44:54,440 --> 00:44:55,508
THINK ABOUT THIS A LOT BECAUSE 

974
00:44:55,508 --> 00:44:57,777
ONE OF THE UNIQUE CHALLENGES OF 

975
00:44:57,777 --> 00:45:00,480
THE LUNG AND THE AIRWAYS IS IT 

976
00:45:00,480 --> 00:45:02,181
IS REALLY WELL-DESIGNED OVER THE

977
00:45:02,181 --> 00:45:04,817
COURSE OF EVOLUTION TO ACTUALLY 

978
00:45:04,817 --> 00:45:06,619
EXPEL ANYTHING THAT YOU TRY TO 

979
00:45:06,619 --> 00:45:08,988
DELIVER TO IT.  IT HAS A 

980
00:45:08,988 --> 00:45:14,460
PHYSICAL BARRIER OF MUCOUS AND 

981
00:45:14,460 --> 00:45:15,995
ALSO MUCOUS CLEARANCE AND SO 

982
00:45:15,995 --> 00:45:17,463
IT'S ACTUALLY A VERY UNIQUE 

983
00:45:17,463 --> 00:45:19,932
CHALLENGE WE THINK TO GET CELLS 

984
00:45:19,932 --> 00:45:22,168
SAFELY INTO THE AIRWAY SO THIS 

985
00:45:22,168 --> 00:45:24,270
IS A SOMEWHAT ARBITRARY SCHEMA 

986
00:45:24,270 --> 00:45:27,740
OF WHAT WE SEE AS A PATH TO A 

987
00:45:27,740 --> 00:45:29,709
CURE.  AND I HAVE IDENTIFIED 

988
00:45:29,709 --> 00:45:33,046
WHAT OUR GROUP THINKS OF AS SOME

989
00:45:33,046 --> 00:45:36,249
REALLY, REALLY KEY NEXT STEP 

990
00:45:36,249 --> 00:45:38,451
RESEARCH HURDLES TO TRY AND 

991
00:45:38,451 --> 00:45:41,788
TACKLE.  ANIMAL MODELS ARE A 

992
00:45:41,788 --> 00:45:45,625
MAJOR NEXT STEP FOR US.  AND IN 

993
00:45:45,625 --> 00:45:47,393
TERMS OF THIS WORKSHOP, THE 

994
00:45:47,393 --> 00:45:50,596
OBVIOUS ISSUES THERE ARE THE 

995
00:45:50,596 --> 00:45:53,132
COST AND THE EXPERTISE REQUIRED 

996
00:45:53,132 --> 00:45:55,001
TO DO SOME OF THESE STUDIES IN 

997
00:45:55,001 --> 00:45:57,470
LARGER ANIMAL MODELS, SO, 

998
00:45:57,470 --> 00:45:58,838
SPECIFICALLY FOR THE LUNGS, SOME

999
00:45:58,838 --> 00:46:02,709
OF THE BEST ANIMAL MODELS WHERE 

1000
00:46:02,709 --> 00:46:05,211
YOU CAN TRY TO CURE DISEASE 

1001
00:46:05,211 --> 00:46:07,113
WOULD BE SOMETHING LIKE THE 

1002
00:46:07,113 --> 00:46:08,281
FERRET AND THESE ARE VERY 

1003
00:46:08,281 --> 00:46:10,683
EXPENSIVE MODELS THAT ARE NOT 

1004
00:46:10,683 --> 00:46:14,153
EASILY FUNDED.  THE OTHER POINT 

1005
00:46:14,153 --> 00:46:15,822
I WANTED TO THEN MAKE IS 

1006
00:46:15,822 --> 00:46:17,690
DELIVERY.  DELIVERY TO THE LUNG 

1007
00:46:17,690 --> 00:46:19,025
IS A HUGE CHALLENGE.  AND SO 

1008
00:46:19,025 --> 00:46:21,194
WE'RE MAINLY TALKING ABOUT CELL 

1009
00:46:21,194 --> 00:46:23,663
BASED THERAPIES BUT THE GENE 

1010
00:46:23,663 --> 00:46:26,432
THERAPY, GENE EDITING MACHINERY 

1011
00:46:26,432 --> 00:46:27,800
WHILE WE MADE HUGE PROGRESS 

1012
00:46:27,800 --> 00:46:30,603
WHILE IT GET TO THE POINT OF 

1013
00:46:30,603 --> 00:46:32,205
ACHIEVING DELIVERY TO THE 

1014
00:46:32,205 --> 00:46:33,840
AIRWAYS OR COMPARTMENTS WE HAVE 

1015
00:46:33,840 --> 00:46:36,275
A LOT OF WORK TO DO AND SO OUR 

1016
00:46:36,275 --> 00:46:38,277
THINKING IS THAT REALLY NOW WE 

1017
00:46:38,277 --> 00:46:40,079
NEED TO CREATE AN ENTIRELY NEW 

1018
00:46:40,079 --> 00:46:42,081
RESEARCH PROGRAM DIRECTION WHICH

1019
00:46:42,081 --> 00:46:43,816
IS HOW TO ACTUALLY DELIVER TO 

1020
00:46:43,816 --> 00:46:45,752
THE LUNG, NEVER AS A FIELD 

1021
00:46:45,752 --> 00:46:48,287
BEFORE HAVE WE REALLY HAD TO TRY

1022
00:46:48,287 --> 00:46:50,623
TO DELIBERATELY INDUCE TOLERATED

1023
00:46:50,623 --> 00:46:52,658
LUNG INJURY.  MOST OF THE WORK 

1024
00:46:52,658 --> 00:46:54,927
TO DATE HAS BEEN INDUCING LUNG 

1025
00:46:54,927 --> 00:46:56,529
INJURY IN ANIMAL MODELS TO 

1026
00:46:56,529 --> 00:46:57,830
UNDERSTAND THE BIOLOGY OF 

1027
00:46:57,830 --> 00:46:59,298
REGENERATION BUT NOW I THINK WE 

1028
00:46:59,298 --> 00:47:01,267
NEED A VERY CONCERTED EFFORT 

1029
00:47:01,267 --> 00:47:03,836
FROM THE VERY MICROSCOPIC OF 

1030
00:47:03,836 --> 00:47:05,738
UNDERSTANDING LUNG REGENERATION 

1031
00:47:05,738 --> 00:47:08,975
TO THE MORE MACROSCOPIC 

1032
00:47:08,975 --> 00:47:11,844
BIOENGINEERING APPROACHES TO HOW

1033
00:47:11,844 --> 00:47:13,713
WE EFFICIENTLY DELIVER CELL TO 

1034
00:47:13,713 --> 00:47:15,982
SUCH A LARGE SURFACE AREA IS 

1035
00:47:15,982 --> 00:47:17,850
WHAT IS NOW REQUIRED. 

1036
00:47:17,850 --> 00:47:20,620
SO THIS IS JUST TO THEN 

1037
00:47:20,620 --> 00:47:21,821
ACKNOWLEDGE THE TEAM WHO DID THE

1038
00:47:21,821 --> 00:47:25,258
WORK AND THANK YOU FOR YOUR 

1039
00:47:25,258 --> 00:47:34,467
TIM

1040
00:47:34,467 --> 00:47:35,835
TIME

1041
00:47:35,835 --> 00:47:37,737
TIME.  ANY .

1042
00:47:37,737 --> 00:47:46,479
>> THANK YOU, FINN.  YING
AND 

1043
00:47:46,479 --> 00:47:47,780
THEN CHRISTOPHER BREAUXER.

1044
00:47:47,780 --> 00:47:49,348
>> THANK YOU.  THANK YOU
TO THE 

1045
00:47:49,348 --> 00:47:50,817
ORGANIZERS FOR THE OPPORTUNITY 

1046
00:47:50,817 --> 00:47:52,885
TO TALK ABOUT MY PROJECT AND 

1047
00:47:52,885 --> 00:47:55,655
THAT SHARE OUR INSIGHTS ABOUT 

1048
00:47:55,655 --> 00:47:59,125
THE -- OUR PERSPECTIVE ABOUT 

1049
00:47:59,125 --> 00:48:02,628
REGENERATIVE MEDICINE AND MY 

1050
00:48:02,628 --> 00:48:06,065
RMIP PROJECT IS THE ORGANOID 

1051
00:48:06,065 --> 00:48:08,034
TREATING.  LET'S START WITH THE 

1052
00:48:08,034 --> 00:48:08,634
CLINICAL NEEDS I DON'T THINK 

1053
00:48:08,634 --> 00:48:10,603
WITH THIS AUDIENCE I NEED TO 

1054
00:48:10,603 --> 00:48:14,907
CONVINCE YOU THAT INFECTION IS A

1055
00:48:14,907 --> 00:48:19,579
PROBLEM AND THIS IS EMERGING AS 

1056
00:48:19,579 --> 00:48:21,647
WE IMPROVE CELLS FOR TREATING.  

1057
00:48:21,647 --> 00:48:27,019
THE TRADITIONAL WAY TO TREATING 

1058
00:48:27,019 --> 00:48:30,122
MYOCARDIAL INFARCTION IS TO 

1059
00:48:30,122 --> 00:48:30,823
INJECTING.  THE PROBLEM IS THE 

1060
00:48:30,823 --> 00:48:33,693
HEART IS, YOU KNOW, CONSTANTLY 

1061
00:48:33,693 --> 00:48:36,128
PUMPING SO IT'S ALMOST INSTANTLY

1062
00:48:36,128 --> 00:48:38,764
PUMP OUT INTO CIRCULATION AND 

1063
00:48:38,764 --> 00:48:41,434
THE LEADING PRETTY LOW, LIKE, 

1064
00:48:41,434 --> 00:48:43,502
YOU KNOW, CELL RETENTION AND 

1065
00:48:43,502 --> 00:48:45,905
SURVIVAL AND LEADING TO MODERATE

1066
00:48:45,905 --> 00:48:49,275
FUNCTION AND RECOVERY AND THE 

1067
00:48:49,275 --> 00:48:51,878
HUMAN COST.  BECAUSE THE CELLS, 

1068
00:48:51,878 --> 00:48:54,680
IS THEY JUST, THEY DON'T 

1069
00:48:54,680 --> 00:48:56,415
NECESSARILY COORDINATE WITH THE 

1070
00:48:56,415 --> 00:49:01,988
HEARTS TO ADDRESS THIS ISSUE, WE

1071
00:49:01,988 --> 00:49:04,123
PROPOSING TO DEVELOP THIS ORGAN 

1072
00:49:04,123 --> 00:49:06,692
NOWED SYSTEM AND, YOU KNOW, WE 

1073
00:49:06,692 --> 00:49:08,895
ESSENTIALLY TRY TO HAVE OUR 

1074
00:49:08,895 --> 00:49:15,534
IDEAS DEVELOP AN INJECTABLE 

1075
00:49:15,534 --> 00:49:16,535
ORGANOIDS. 

1076
00:49:16,535 --> 00:49:25,244
AND AN ASSEMBLY OF CUTTING OF 

1077
00:49:25,244 --> 00:49:25,945
FIBROBL

1078
00:49:25,945 --> 00:49:26,779
FIBROBLASTS.  THE ISSUES 

1079
00:49:26,779 --> 00:49:28,881
CONTRACT AND THERE'S THE REGION 

1080
00:49:28,881 --> 00:49:32,351
OF THE PERIPHERY OF THE 

1081
00:49:32,351 --> 00:49:33,185
ORGANOIDS AND FORMING THIS 

1082
00:49:33,185 --> 00:49:34,787
STRUCTURE WITHIN THE ORGANOIDS 

1083
00:49:34,787 --> 00:49:38,124
AND THE IDEA HERE IS IF YOU MAKE

1084
00:49:38,124 --> 00:49:41,827
AN INSTEAD OF THE CELLS YOU HAVE

1085
00:49:41,827 --> 00:49:44,463
A TISSUE THIS BETTER SUSTAIN THE

1086
00:49:44,463 --> 00:49:45,097
SHEER FORCE OF THE CONTRACTION 

1087
00:49:45,097 --> 00:49:49,101
AND MAKE IT A BETTER STAY IN THE

1088
00:49:49,101 --> 00:49:53,239
MYOCARDIUM AND MAKE IT BETTER 

1089
00:49:53,239 --> 00:49:54,607
SURVIVE IN THE ENVIRONMENT.  ON 

1090
00:49:54,607 --> 00:49:58,511
TOP OF THAT WE WANT TO 

1091
00:49:58,511 --> 00:50:00,146
INCORPORATE THE ANCILLARY 

1092
00:50:00,146 --> 00:50:01,247
INTEGRATION WITH THE HOST HEART 

1093
00:50:01,247 --> 00:50:03,582
TO IMPROVE THEIR FUNCTIONAL 

1094
00:50:03,582 --> 00:50:05,084
PERFORMANCE AND WE ARE FORTUNATE

1095
00:50:05,084 --> 00:50:07,620
TO RECEIVING OUR SUPPORT TO 

1096
00:50:07,620 --> 00:50:13,960
PURSUE THIS IDEA.  AND RECENT 

1097
00:50:13,960 --> 00:50:14,560
SUPPORT WE HAVE THE ORGANOID 

1098
00:50:14,560 --> 00:50:16,262
THAT COMES WITH A BETTER 

1099
00:50:16,262 --> 00:50:18,097
FUNCTIONAL RECOVERY WITH ONLY 

1100
00:50:18,097 --> 00:50:20,666
10% OF CELLS COMPARED TO THE 

1101
00:50:20,666 --> 00:50:23,135
CURRENT STATE OF ART.  WE HAVE 

1102
00:50:23,135 --> 00:50:25,838
THE PERFUSION MODEL BUT WITH THE

1103
00:50:25,838 --> 00:50:27,006
CLINICAL TRANSLATION THERE'S 

1104
00:50:27,006 --> 00:50:31,744
RIGHT NOW WITH THE IPSA MOUSE.  

1105
00:50:31,744 --> 00:50:33,813
WE HAVE THE CELLS THAT COME FROM

1106
00:50:33,813 --> 00:50:36,349
DIFFERENT DONOR LEADING TO 

1107
00:50:36,349 --> 00:50:38,117
UNDEFINED EXPRESSIONS.  ON TOP 

1108
00:50:38,117 --> 00:50:40,586
OF THAT AS OF RIGHT NOW WE CAST 

1109
00:50:40,586 --> 00:50:44,190
THIS IN THE RED MODEL BUT THE 

1110
00:50:44,190 --> 00:50:45,524
FREQUENCY OF THE RED HEARTBEAT 

1111
00:50:45,524 --> 00:50:48,561
IS BEATING TOO FAST MAKING THAT 

1112
00:50:48,561 --> 00:50:51,197
AN IDEAL MODEL TO TEST THE 

1113
00:50:51,197 --> 00:50:54,600
IMPLANTED ORGANOIDS.  SO THE 

1114
00:50:54,600 --> 00:50:57,203
RMIP PROJECT IS UNIQUE.  IT'S A 

1115
00:50:57,203 --> 00:50:59,138
WONDERFUL OPPORTUNITY AS A 

1116
00:50:59,138 --> 00:50:59,972
TECHNOLOGY DEVELOPMENT TO GRANT 

1117
00:50:59,972 --> 00:51:02,475
TO US TO FACILITATE IN THE 

1118
00:51:02,475 --> 00:51:04,977
CLINICAL TRANSLATION OF THE -- 

1119
00:51:04,977 --> 00:51:08,748
OUR TECHNOLOGY SO IN THE RMIP 

1120
00:51:08,748 --> 00:51:09,782
PROJECT IT WOULD BE INTERESTING 

1121
00:51:09,782 --> 00:51:12,051
TO SAY WHETHER INSTEAD OF USING 

1122
00:51:12,051 --> 00:51:13,586
CELLS FROM DIFFERENT DONOR WE 

1123
00:51:13,586 --> 00:51:21,560
USE ONE SINGLE, LIKE AN IPSC 

1124
00:51:21,560 --> 00:51:25,765
DONOR TO DERIVE THE CELLS AND TO

1125
00:51:25,765 --> 00:51:29,935
MAKING ORGANOIDS TO POTENTIALLY 

1126
00:51:29,935 --> 00:51:31,704
PROVIDE ALSO THERAPY AND WE WANT

1127
00:51:31,704 --> 00:51:34,273
TO DERIVE THOSE CELLS AND 

1128
00:51:34,273 --> 00:51:41,047
FABRICATE THE ORGANOID IN THE 

1129
00:51:41,047 --> 00:51:42,214
CRITICAL CONDITIONS AND HAVE THE

1130
00:51:42,214 --> 00:51:45,351
EFFICACY TO TEST THEM IN LIKE A 

1131
00:51:45,351 --> 00:51:47,887
LARGER ANIMAL OR MODEL.  SO, YOU

1132
00:51:47,887 --> 00:51:49,555
KNOW, TO -- IN TERMS OF THE 

1133
00:51:49,555 --> 00:51:52,124
QUESTION ABOUT THE, YOU KNOW, 

1134
00:51:52,124 --> 00:51:54,093
THE CHALLENGES AND OPPORTUNITIES

1135
00:51:54,093 --> 00:51:57,063
I THINK IT'S LIKE A -- WELL 

1136
00:51:57,063 --> 00:51:59,265
DURING -- DURING OUR OWN, LIKE, 

1137
00:51:59,265 --> 00:52:00,933
YOU KNOW, TRANSLATION, ONE OF 

1138
00:52:00,933 --> 00:52:03,969
THE THINGS THAT WE FEEL WERE THE

1139
00:52:03,969 --> 00:52:05,604
CHALLENGES IS THEY NEED A 

1140
00:52:05,604 --> 00:52:07,740
BLUEPRINT OF SAFETY TRACK TO 

1141
00:52:07,740 --> 00:52:12,211
MOVE INTO THE CELL THERAPY OF 

1142
00:52:12,211 --> 00:52:15,815
CLINICAL TRIALS FIRSTLY THE CELL

1143
00:52:15,815 --> 00:52:17,683
MANUFACTURER.  YOU HAVE THE CELL

1144
00:52:17,683 --> 00:52:19,151
GENERATION, THE LINE SELECTIONS,

1145
00:52:19,151 --> 00:52:24,490
LIKE THE ONECIDE  -- ONE SIZE 

1146
00:52:24,490 --> 00:52:26,358
FITS ALL FOR DIFFERENT DISEASE 

1147
00:52:26,358 --> 00:52:28,494
YOU NEED DIFFERENT LINES.  AND 

1148
00:52:28,494 --> 00:52:31,130
THE FIELD IS MOVING TO DOING A 

1149
00:52:31,130 --> 00:52:32,598
SAFETY CHECK.  AND EXPANSION.  

1150
00:52:32,598 --> 00:52:35,201
SCALE UP.  IT'S ONE THING TO 

1151
00:52:35,201 --> 00:52:36,735
MAKING A FEW CELL TO TREAT A RAT

1152
00:52:36,735 --> 00:52:38,404
BUT IT'S DIFFERENT IF YOU WANT 

1153
00:52:38,404 --> 00:52:39,872
TO MAKE BILLIONS OF CELLS TO 

1154
00:52:39,872 --> 00:52:42,074
TREATING THE, YOU KNOW, TREATING

1155
00:52:42,074 --> 00:52:45,444
THE PATIENT.  AND THE CRYO 

1156
00:52:45,444 --> 00:52:47,046
PRESERVATION.  WE LOST A LOT OF 

1157
00:52:47,046 --> 00:52:47,880
CELLS DURING THIS. 

1158
00:52:47,880 --> 00:52:51,784
CAN WE IMPROVE IT?  LIKE THE 

1159
00:52:51,784 --> 00:52:54,753
TUMOR GENESISTY AND LIKE A TEAM 

1160
00:52:54,753 --> 00:52:56,655
SAID WHERE IS THE GAP?  WE NEED 

1161
00:52:56,655 --> 00:52:59,125
TO ADDRESS THE GAP BETWEEN THE 

1162
00:52:59,125 --> 00:53:00,693
ORIGIN MODEL AND THE PATIENT.  

1163
00:53:00,693 --> 00:53:03,028
RIGHT NOW OUR REVIEW ABOUT THE 

1164
00:53:03,028 --> 00:53:05,831
CELL, LIKE A CELL BASED MEDICINE

1165
00:53:05,831 --> 00:53:07,867
IS THE ALOE GENERALIC.  THEN 

1166
00:53:07,867 --> 00:53:14,073
RIGHT NOW WITH PEOPLE FOCUS ON, 

1167
00:53:14,073 --> 00:53:21,213
WE HAVE A HUMANIZED BY  BUT DO 

1168
00:53:21,213 --> 00:53:22,815
WE NEED OTHER TECHNOLOGIES?

1169
00:53:22,815 --> 00:53:24,316
LAST BUT NOT LEAST IS A 

1170
00:53:24,316 --> 00:53:25,017
WORKFORCE DEVELOPMENT.  THANK 

1171
00:53:25,017 --> 00:53:28,420
YOU FOR YOUR ATTENTION.  THANK 

1172
00:53:28,420 --> 00:53:36,695
YOU

1173
00:53:36,695 --> 00:53:36,862
YOU.

1174
00:53:36,862 --> 00:53:39,532
>> I UNDERSTAND THAT
CHRISTOPHER

1175
00:53:39,532 --> 00:53:41,667
BREWER IS STILL WORKING TO GET 

1176
00:53:41,667 --> 00:53:43,969
HERE SO WE'LL SAVE THAT AND HAVE

1177
00:53:43,969 --> 00:53:48,340
TO COME BACK, JEFFREY STERN IF 

1178
00:53:48,340 --> 00:53:53,512
YOU COULD.  WE HAD TO SKIP ONE 

1179
00:53:53,512 --> 00:54:04,023
OF THE TALKS.  THANK YOU.  DO 

1180
00:54:12,464 --> 00:54:16,468
HOPE THAT CHRISTOPHER SHOWS UP. 

1181
00:54:16,468 --> 00:54:24,109
BUT -- A.

1182
00:54:24,109 --> 00:54:29,448
>> HOW DO YOU ADVANCE THIS
GOOD 

1183
00:54:29,448 --> 00:54:31,116
MORNING I WILL DISCUSS A 

1184
00:54:31,116 --> 00:54:32,418
CHALLENGE WE'RE ALL FAMILIAR 

1185
00:54:32,418 --> 00:54:34,887
WITH.  HOW DO WE CHARACTERIZE A 

1186
00:54:34,887 --> 00:54:36,822
DRUG SUBSTANCE?  AND 

1187
00:54:36,822 --> 00:54:39,225
TRADITIONALLY WE USE IDENTITY, 

1188
00:54:39,225 --> 00:54:42,494
PURITY, AND POTENCY.  I'M GOING 

1189
00:54:42,494 --> 00:54:47,099
TO FOCUS ON IDENTITY.  WHAT IS 

1190
00:54:47,099 --> 00:54:50,903
THE DRUG SUBSTANCE?  IF I CAN 

1191
00:54:50,903 --> 00:54:57,343
WORK THIS SLIDE DECK.  

1192
00:54:57,343 --> 00:55:01,113
TRADITIONALLY SINCE 1906 THE FDA

1193
00:55:01,113 --> 00:55:03,916
AS USED MOLECULAR FORMULA TO 

1194
00:55:03,916 --> 00:55:06,986
VERY PRECISELY DESCRIBE A DRUG. 

1195
00:55:06,986 --> 00:55:12,191
THIS DOESN'T WORK VERY WELL FOR 

1196
00:55:12,191 --> 00:55:14,393
CELLS.  AND POINTS TO THE 

1197
00:55:14,393 --> 00:55:15,261
CHALLENGE, HOW DO WE DESCRIBE 

1198
00:55:15,261 --> 00:55:19,198
THE IDENTITY OF A LIVING CELL 

1199
00:55:19,198 --> 00:55:26,038
PRODUCT?  I APOLOGIZE FOR TH

1200
00:55:26,038 --> 00:55:28,507
THIS -- I'M GOING TO USE ON 

1201
00:55:28,507 --> 00:55:32,244
EXAMPLE OF THE RPE CELL WHICH WE

1202
00:55:32,244 --> 00:55:34,947
WORK ONTO TRANSPLANT TO TREAT 

1203
00:55:34,947 --> 00:55:38,751
MACULAR DEGENERATION TO REVERSE 

1204
00:55:38,751 --> 00:55:42,788
THESE AREAS UNDER THE RETINA AND

1205
00:55:42,788 --> 00:55:46,825
GROW RPE AND INJECTED UNDER THE 

1206
00:55:46,825 --> 00:55:48,527
RETINA IN AN EFFORT TO REVERSE 

1207
00:55:48,527 --> 00:55:50,929
THIS IN A CLINICAL TRIAL WE 

1208
00:55:50,929 --> 00:55:53,098
IDENTIFY THE IDENTITY OF THE 

1209
00:55:53,098 --> 00:55:54,466
CELLS WHICH ARE VERY HOMOGENOUS 

1210
00:55:54,466 --> 00:55:58,604
AND ALL LOOK THE CELL USING 

1211
00:55:58,604 --> 00:56:02,174
ANTIBODIES THAT STAIN FOR RMP 

1212
00:56:02,174 --> 00:56:04,209
SPECIFIC MARKERS AND ALL OF 

1213
00:56:04,209 --> 00:56:07,746
THESE CELLS STAIN FOR RMP 

1214
00:56:07,746 --> 00:56:11,684
MARKERS AND THIS APPROACHES.  IS

1215
00:56:11,684 --> 00:56:15,854
GOOD.  IT WORKS.   BUT I THINK 

1216
00:56:15,854 --> 00:56:19,024
WE CAN DO BETTER THAN AND THE 

1217
00:56:19,024 --> 00:56:22,661
PROGRAM HAS HELPED US MOVE IN 

1218
00:56:22,661 --> 00:56:26,999
THAT DIRECTION.  WE FOUND THAT 

1219
00:56:26,999 --> 00:56:29,702
THE IDENTITY OF A CELL PRODUCT 

1220
00:56:29,702 --> 00:56:33,772
CAN BE, LIKE, BROOKLYN'S 

1221
00:56:33,772 --> 00:56:36,709
DEMOGRAPHIC.  DIVERSE.  CELLS.  

1222
00:56:36,709 --> 00:56:40,679
DIVERSE POPULATIONS OF CELLS.  

1223
00:56:40,679 --> 00:56:42,314
THAT CHANGE OVER TIME THAT EACH 

1224
00:56:42,314 --> 00:56:44,416
HAVE DISTINCT FUNCTIONS AND THAT

1225
00:56:44,416 --> 00:56:46,518
WORK TOGETHER.  WE'D LIKE TO 

1226
00:56:46,518 --> 00:56:52,658
IDENTIFY THE SUBPOPULATION.  I 

1227
00:56:52,658 --> 00:56:55,661
HAD A POINTER.  EXCUSE ME.  WE'D

1228
00:56:55,661 --> 00:56:59,932
LIKE TO IDENTIFY WHICH OF THESE 

1229
00:56:59,932 --> 00:57:01,700
SUBPOPULATIONS CONFERS RESCUE.  

1230
00:57:01,700 --> 00:57:03,902
WHICH OF THESE SUBPOPULATIONS 

1231
00:57:03,902 --> 00:57:08,307
CAUSE THE CELLS TO GRAFT AFTER 

1232
00:57:08,307 --> 00:57:09,541
TRANSPLANTED AND WE'RE MAKING 

1233
00:57:09,541 --> 00:57:12,177
SOME PROGRESS IN THAT DIRECTION 

1234
00:57:12,177 --> 00:57:20,018
FUNDED BY THE RMIP.  SO IT'D BE 

1235
00:57:20,018 --> 00:57:21,820
RMIP HAS FUNDED AND SUPPORT THIS

1236
00:57:21,820 --> 00:57:23,822
HAD IN DEPTH CELL 

1237
00:57:23,822 --> 00:57:26,091
CHARACTERIZATION.  THAT IS 

1238
00:57:26,091 --> 00:57:28,460
LEADING THE WAY TO THE NEXT 

1239
00:57:28,460 --> 00:57:31,830
LEVEL OF DETERMINING A CELL 

1240
00:57:31,830 --> 00:57:34,466
PRODUCT'S IDENTITY.  FOR 

1241
00:57:34,466 --> 00:57:37,069
SUBSEQUENT EVALUATIONS.  WHAT WE

1242
00:57:37,069 --> 00:57:46,345
NEED NEXT, EXCUSE ME, HOW 

1243
00:57:46,345 --> 00:57:49,448
EMBARRASSING.  I AM LOST WITH 

1244
00:57:49,448 --> 00:57:54,086
THE SLIDES.  THE -- WHAT WE NEED

1245
00:57:54,086 --> 00:57:57,089
IS EARLY FDA COMMUNICATION 

1246
00:57:57,089 --> 00:58:00,859
PROGRAMS LIKE THE R MAP, 

1247
00:58:00,859 --> 00:58:02,361
INTERACTING PROGRAM IF WE CAN 

1248
00:58:02,361 --> 00:58:04,797
EXPAND ACCESS FOR THE NIH, FOR 

1249
00:58:04,797 --> 00:58:07,599
THE GRANTEES, SUCH AS OUR 

1250
00:58:07,599 --> 00:58:08,801
OURSELVES TO WORK TOGETHER WITH 

1251
00:58:08,801 --> 00:58:12,938
THE FDA TO OUTLINE THE PATH TO 

1252
00:58:12,938 --> 00:58:13,739
CRYOPRESERVATION, THE SPEAKERS 

1253
00:58:13,739 --> 00:58:16,642
BEFORE ME HAVE MENTIONED OTHER 

1254
00:58:16,642 --> 00:58:19,178
STEPS.  HOW DO WE DETERMINE 

1255
00:58:19,178 --> 00:58:22,080
ENGRAFTMENT?  HOW DO WE CREATE 

1256
00:58:22,080 --> 00:58:26,819
HOMOGENEITY.  HOW DO WE DEFINE 

1257
00:58:26,819 --> 00:58:34,460
HOMO JAY NAYTY TO ACCELERATE 

1258
00:58:34,460 --> 00:58:45,971
CELL DEVELOPMENT.  THDEVELOPME

1259
00:58:47,272 --> 00:58:49,241
>> CHRISTOPHER, OKAY,
YOU'LL BE 

1260
00:58:49,241 --> 00:58:55,113
ON DECK.  OKAY?  SO WHICH ONE --

1261
00:58:55,113 --> 00:58:56,482
YES, YOU CAN COME IN BUT I DON'T

1262
00:58:56,482 --> 00:59:06,992
KNOW WHAT'S YOUR FIRST SLIDE.

1263
00:59:09,895 --> 00:59:11,630
>> GOOD MORNING, I'M GARY,
THANK

1264
00:59:11,630 --> 00:59:13,365
YOU FOR THE INVITATION AND FOR 

1265
00:59:13,365 --> 00:59:17,436
THE CHANCE TO TALK ABOUT THIS 

1266
00:59:17,436 --> 00:59:20,072
PROJECT.  SO MY LAB AT THE 

1267
00:59:20,072 --> 00:59:25,110
UNIVERSITY, STUDY REGENERATION, 

1268
00:59:25,110 --> 00:59:27,079
THIS FUNDING SUPPORTS THE 

1269
00:59:27,079 --> 00:59:30,282
MANUFACTURING OF THE HUMAN CELLS

1270
00:59:30,282 --> 00:59:35,287
OR  AND OUR GOAL IS FOR 

1271
00:59:35,287 --> 00:59:37,022
SCARRING.  SO IN MY PROJECT I 

1272
00:59:37,022 --> 00:59:41,527
HAVE A CO-PI, I'M SORRY, YEAH.  

1273
00:59:41,527 --> 00:59:47,132
OKAY.  SO HE'S THE HEAD OF THE 

1274
00:59:47,132 --> 00:59:48,433
FACILITIES AND TAKES CARE OF THE

1275
00:59:48,433 --> 00:59:50,669
MANUFACTURING AND ALSO THE 

1276
00:59:50,669 --> 00:59:53,038
STUDIES.  SO WE HAVE OVER MORE 

1277
00:59:53,038 --> 00:59:55,307
THAN TEN YEARS WORK THAT WAS LED

1278
00:59:55,307 --> 00:59:59,912
BY THE FORMER PI.  AND ALSO 

1279
00:59:59,912 --> 01:00:02,314
CURRENTLY MYSELF.  THAT WE'RE WE

1280
01:00:02,314 --> 01:00:05,918
HAVE SHOWN HUMANS FOR CELL 

1281
01:00:05,918 --> 01:00:09,054
TREATMENT.  THE FIBROSIS AND 

1282
01:00:09,054 --> 01:00:11,723
ALSO THE SCAR TISSUE.  SO HERE 

1283
01:00:11,723 --> 01:00:12,758
THERE'S THE DIFFERENT MODELS 

1284
01:00:12,758 --> 01:00:16,328
THAT WE HAVE IN OUR EXPERIMENTS.

1285
01:00:16,328 --> 01:00:22,067
SO THE TREATMENT IS SIMPLE THAT 

1286
01:00:22,067 --> 01:00:24,536
WE PLACE IT TOPICALLY AND AFTER,

1287
01:00:24,536 --> 01:00:29,441
IN A DROP, IN THE GMP.  SO AFTER

1288
01:00:29,441 --> 01:00:32,744
TWO WEEKS OR LONGER DEPENDING ON

1289
01:00:32,744 --> 01:00:34,846
EXPERIMENTS THOSE CONTROLS THAT 

1290
01:00:34,846 --> 01:00:37,749
DO NOT RECEIVE THE TREATMENTS, 

1291
01:00:37,749 --> 01:00:40,819
THEY DEVELOP OPACITIES.  BUT FOR

1292
01:00:40,819 --> 01:00:44,990
THOSE CORNEAS, TREATED WITH STEM

1293
01:00:44,990 --> 01:00:46,625
CELLS THEY HAVE MUCH CLEAR 

1294
01:00:46,625 --> 01:00:48,627
CORNEAS AND VERY SUPPRESSED 

1295
01:00:48,627 --> 01:00:50,562
SCARRING AND OPACITIES AND ALSO 

1296
01:00:50,562 --> 01:00:53,198
THE EXPRESSIONS OF THE VARIOUS 

1297
01:00:53,198 --> 01:00:56,902
IMAGERY AND ALSO THE FIBROSIS 

1298
01:00:56,902 --> 01:00:59,137
MARKERS ARE SIGNIFICANTLY 

1299
01:00:59,137 --> 01:01:00,572
REDUCED.  SO THESE RESULTS ARE 

1300
01:01:00,572 --> 01:01:02,474
HIGHLY REPRODUCIBLES IN OUR 

1301
01:01:02,474 --> 01:01:06,345
DIFFERENT ANIMAL EXPERIMENTS AND

1302
01:01:06,345 --> 01:01:09,014
WITH DIFFERENT STEM CELLS.  SO 

1303
01:01:09,014 --> 01:01:11,550
AND ALSO WE REPORTED MECHANISMS 

1304
01:01:11,550 --> 01:01:13,385
OF THE STEM CELL TREATMENT THAT 

1305
01:01:13,385 --> 01:01:15,153
INVOLVES THE ACTIVITIES MEANING 

1306
01:01:15,153 --> 01:01:17,522
IT'S PART OF THE EXPRESSIONS.  

1307
01:01:17,522 --> 01:01:21,159
AND ALSO THE STEM CELLS 

1308
01:01:21,159 --> 01:01:24,096
DIFFERENTIATE WITH THE CELL 

1309
01:01:24,096 --> 01:01:25,330
TYPE.  SO THIS CAN HELP.  THIS 

1310
01:01:25,330 --> 01:01:30,002
CAN DEPOSIT THE ECM PROTEIN AND 

1311
01:01:30,002 --> 01:01:34,039
ALSO THE STROMAL MODELING THAT 

1312
01:01:34,039 --> 01:01:35,140
HAS CONFIGURATIONS AND ALSO THE 

1313
01:01:35,140 --> 01:01:39,645
STROMAL STEM CELLS REDUCED.  AND

1314
01:01:39,645 --> 01:01:42,848
ALSO THE ANTIFIBROSIS MICRO RNA 

1315
01:01:42,848 --> 01:01:45,250
AS WELL AS THE XO SOMES THAT WE 

1316
01:01:45,250 --> 01:01:47,486
ARE CURRENTLY EXPLORING IN THE 

1317
01:01:47,486 --> 01:01:47,886
MOLECULES. 

1318
01:01:47,886 --> 01:01:49,755
AND FOR THE LATEST DEVELOPMENT 

1319
01:01:49,755 --> 01:01:50,989
IN THIS PROJECT THAT WE HAVE 

1320
01:01:50,989 --> 01:01:56,028
ALREADY OPTIMIZED THE GMP SOP 

1321
01:01:56,028 --> 01:01:57,963
FOR THE CULTURE PROPAGATIONS AND

1322
01:01:57,963 --> 01:02:00,599
SO ON AND ALSO SO THAT'S WHY 

1323
01:02:00,599 --> 01:02:03,035
WITH THIS -- WITH THIS RMIP 

1324
01:02:03,035 --> 01:02:04,269
FUNDING WE WILL START THE 

1325
01:02:04,269 --> 01:02:07,839
MANUFACTURING OF THE CELLS AND 

1326
01:02:07,839 --> 01:02:09,341
ALSO THESE STROMAL STEM CELLS 

1327
01:02:09,341 --> 01:02:13,945
ARE ACE  ISOLATED SO THAT'S WHY 

1328
01:02:13,945 --> 01:02:17,983
WE ALSO ESTABLISHED A QCSH FOR 

1329
01:02:17,983 --> 01:02:19,951
THE CELLS AND CALCULATE THE 

1330
01:02:19,951 --> 01:02:21,286
SCARRING INDEX FOR DIFFERENT 

1331
01:02:21,286 --> 01:02:23,789
STEM CELL BATCHES TO PROTECT THE

1332
01:02:23,789 --> 01:02:27,893
IN VIVO POTENCY OF THE CELLS. 

1333
01:02:27,893 --> 01:02:30,228
AND WE HAVE FOUND THIS.  AND 

1334
01:02:30,228 --> 01:02:32,698
CURRENTLY WE ARE LOOKING ON THE 

1335
01:02:32,698 --> 01:02:34,933
ANIMAL MODELS WITH THE STEM 

1336
01:02:34,933 --> 01:02:37,335
CELLS TREATING THE ANIMAL MODEL 

1337
01:02:37,335 --> 01:02:40,539
WITH THE CHRONIC OPACITIES AND 

1338
01:02:40,539 --> 01:02:42,974
SO FAR IS PRETTY GOOD AND PRETTY

1339
01:02:42,974 --> 01:02:44,609
ENCOURAGING AND WE ARE WORK ON 

1340
01:02:44,609 --> 01:02:47,479
DEFINING THE MECHANISMS OF 

1341
01:02:47,479 --> 01:02:49,448
ACTIONS SO OUR GOAL IS TO 

1342
01:02:49,448 --> 01:02:50,649
APPRISE THIS STEM CELL TREATMENT

1343
01:02:50,649 --> 01:02:57,622
WITH A NONNATIVE APPROACH OR 

1344
01:02:57,622 --> 01:03:01,693
APPLICATIONS TO PROTECT AND THE 

1345
01:03:01,693 --> 01:03:02,894
ALTERNATIVES FOR THE HIGHLY OR 

1346
01:03:02,894 --> 01:03:07,099
HEAVILY RELIED ON THE DONOR 

1347
01:03:07,099 --> 01:03:09,801
MATERIALS WHICH IS A WORLDWIDE 

1348
01:03:09,801 --> 01:03:11,803
HEALTH CARE ISSUES.  SO WITH 

1349
01:03:11,803 --> 01:03:14,272
THIS RMIP FUNDING WE WILL START 

1350
01:03:14,272 --> 01:03:17,008
OUR CELL MANUFACTURING FOLLOWED 

1351
01:03:17,008 --> 01:03:21,747
BY CMC STUDIES TO LOOK AT CELL 

1352
01:03:21,747 --> 01:03:25,117
SAFETY AND ALSO METABOLIC 

1353
01:03:25,117 --> 01:03:26,184
PROFILING AND ALSO THE MET TAB 

1354
01:03:26,184 --> 01:03:28,186
LYMPHS COMPARED WITH THE LAB 

1355
01:03:28,186 --> 01:03:30,255
BASED CELLS. 

1356
01:03:30,255 --> 01:03:31,890
AND ALSO WE WILL USE THIS UPON 

1357
01:03:31,890 --> 01:03:35,761
THE STEM CELL, USE THESE GMP 

1358
01:03:35,761 --> 01:03:37,662
STEM CELLS FOR THE ANIMAL 

1359
01:03:37,662 --> 01:03:39,498
EXPERIMENT TO LOOK AT THE IN 

1360
01:03:39,498 --> 01:03:41,266
VIVO CELL SAFETY, THE TREATMENT 

1361
01:03:41,266 --> 01:03:46,338
SAFETY, ADVOCACY AND ALSO THE 

1362
01:03:46,338 --> 01:03:48,840
ADME AND DO SOME DATA MINING FOR

1363
01:03:48,840 --> 01:03:51,443
THE NEXT PLAN SUBMISSIONS.  SO 

1364
01:03:51,443 --> 01:03:53,078
WHILE WE ARE WORKING ON 

1365
01:03:53,078 --> 01:03:54,312
DIFFERENT THINGS THERE ARE 

1366
01:03:54,312 --> 01:03:55,647
SEVERAL ISSUES THAT CAN BE 

1367
01:03:55,647 --> 01:03:56,982
CONSIDERED AS CHALLENGES FOR 

1368
01:03:56,982 --> 01:03:58,550
THIS STEM CELL TREATMENT BEFORE 

1369
01:03:58,550 --> 01:04:00,786
WE PUT THEM TO THE 

1370
01:04:00,786 --> 01:04:01,853
APPLICATIONS -- AT THE 

1371
01:04:01,853 --> 01:04:04,356
APPLICATION.  FIRST IS THE STEM 

1372
01:04:04,356 --> 01:04:09,761
CELL FACE CHANGES WHETHER THEY 

1373
01:04:09,761 --> 01:04:15,467
ARE STILL MAINTAINED THE STEM 

1374
01:04:15,467 --> 01:04:19,237
CELL FUNCTIONS.  SO THIS CAN BE 

1375
01:04:19,237 --> 01:04:21,473
POSSIBLY ANSWERED BY SINGLE 

1376
01:04:21,473 --> 01:04:24,242
CELL -- THE SINGLE CELL AND ALSO

1377
01:04:24,242 --> 01:04:27,345
THE STUDIES AND SO ON AND ALSO 

1378
01:04:27,345 --> 01:04:29,481
HOW THIS CHANGES ESPECIALLY IN 

1379
01:04:29,481 --> 01:04:33,718
THE DEPOSIT, THE ECM PROTEINS 

1380
01:04:33,718 --> 01:04:36,021
PRODUCED BY THE TRANSPONDER STEM

1381
01:04:36,021 --> 01:04:38,790
CELLS SO THIS CAN BE STUDIED BY 

1382
01:04:38,790 --> 01:04:44,563
THE HIGH RESOLUTION AND CAPPITUE

1383
01:04:44,563 --> 01:04:46,131
CAPTURING TO STUDY AS WELL AS 

1384
01:04:46,131 --> 01:04:47,132
THE MATRIX REORDERING.  SO FOR 

1385
01:04:47,132 --> 01:04:50,468
THIS WE NEED THE EXPERT TO 

1386
01:04:50,468 --> 01:04:51,703
COLLABORATE WITH A DIFFERENT 

1387
01:04:51,703 --> 01:04:54,039
EXPERT AND THIS IS A CHANCE TO 

1388
01:04:54,039 --> 01:04:55,140
STUDY SOME RESEARCH ON THIS 

1389
01:04:55,140 --> 01:04:59,144
PROJECT.  SO THIS IS KIND OF A 

1390
01:04:59,144 --> 01:05:00,345
SHORT SUMMARY OF OUR PROJECT AND

1391
01:05:00,345 --> 01:05:02,814
OUR PRESENTERS.  AND ALSO THE 

1392
01:05:02,814 --> 01:05:03,849
DIFFERENT CHALLENGES AND I 

1393
01:05:03,849 --> 01:05:04,850
WELCOME YOUR SUGGESTION AND ALSO

1394
01:05:04,850 --> 01:05:08,220
YOUR COMMENTS.  THANK YOU VERY 

1395
01:05:08,220 --> 01:05:18,330
MUC

1396
01:05:19,231 --> 01:05:19,364
MUCH.

1397
01:05:19,364 --> 01:05:21,066
>> CHRISTOPHER, YOU HAVE A
CLANS

1398
01:05:21,066 --> 01:05:22,400
TO HANG YOUR COAT UP?

1399
01:05:22,400 --> 01:05:23,301
>> I DID.

1400
01:05:23,301 --> 01:05:27,706
>> I SO I THINK WE BACK UP

1401
01:05:27,706 --> 01:05:30,542
THAT'S YOU.  OKAY.  THIS ONE.  

1402
01:05:30,542 --> 01:05:34,613
OH -- AND THEN RANDALL KIMBALL 

1403
01:05:34,613 --> 01:05:35,213
WILL BE ON DECK.

1404
01:05:35,213 --> 01:05:40,886
>> GOOD MORNING, MY NAME'S
CHRIS

1405
01:05:40,886 --> 01:05:43,788
I'M FROM COLUMBUS, OHIO AND I 

1406
01:05:43,788 --> 01:05:45,657
HAD THE GOOD FORTUNE TO WORK 

1407
01:05:45,657 --> 01:05:46,791
WITH THE PROGRAM ON MY PROJECT 

1408
01:05:46,791 --> 01:05:49,160
DEVELOPING TISSUE ENGINEERED 

1409
01:05:49,160 --> 01:05:51,696
VASCULAR GRAFT.  THE TISSUE 

1410
01:05:51,696 --> 01:05:55,133
ENGINEERED VASCULAR DWRAFT  

1411
01:05:55,133 --> 01:05:57,636
GRAFT IS A COMBINATION PROJECT. 

1412
01:05:57,636 --> 01:06:07,379
THE DEVICE SPOENT  COMPONENT IS 

1413
01:06:07,379 --> 01:06:09,147
BIODEGRADABLE AND THIS IS 

1414
01:06:09,147 --> 01:06:10,682
HARVESTED ON THE SAME SCAFFOLD 

1415
01:06:10,682 --> 01:06:12,984
THAT IT'S IMPLANTED AND THIS IS 

1416
01:06:12,984 --> 01:06:14,486
OUR SECOND CLINICAL TRIAL 

1417
01:06:14,486 --> 01:06:16,621
EVALUATE THING CONSTRUCT.  THE 

1418
01:06:16,621 --> 01:06:17,856
RATIONALE FOR DEVELOPING IT IS 

1419
01:06:17,856 --> 01:06:20,625
IT'S A LIVING VAS YOU LOW GRAFT 

1420
01:06:20,625 --> 01:06:22,460
SO IT CAN GROW WITH CHILDREN 

1421
01:06:22,460 --> 01:06:23,061
WHEN IT'S IMPLANTED. 

1422
01:06:23,061 --> 01:06:25,764
AND WHAT WE'RE TRYING TO DO WITH

1423
01:06:25,764 --> 01:06:28,967
THE RMIP PROJECT NOW IS TO 

1424
01:06:28,967 --> 01:06:29,968
DEVELOP BETTER RELEASE CRITERIA 

1425
01:06:29,968 --> 01:06:32,170
WE KNOW QUITE A BIT ABOUT THE 

1426
01:06:32,170 --> 01:06:35,941
MECHANISM OF ACTION OF HOW THE 

1427
01:06:35,941 --> 01:06:38,810
TISSUE TRANSFORMS FROM A BIO 

1428
01:06:38,810 --> 01:06:41,079
DEGRADABLE SCAFFOLD TO A LIVING 

1429
01:06:41,079 --> 01:06:42,047
BLOOD VESSEL AND THERE ARE THREE

1430
01:06:42,047 --> 01:06:43,448
IMPORTANT POINTS THE FIRST IS 

1431
01:06:43,448 --> 01:06:45,483
THAT IT -- THE CELLS THAT ARE 

1432
01:06:45,483 --> 01:06:46,985
SEATED ON TO THE SCAFFOLD ARE 

1433
01:06:46,985 --> 01:06:50,388
NOT THE CELLS THAT MAKE THE 

1434
01:06:50,388 --> 01:06:52,324
NEOTISSUE.  THE NEOTISSUE IS 

1435
01:06:52,324 --> 01:06:55,060
DERIVED FROM THE VESSEL.  SECOND

1436
01:06:55,060 --> 01:06:57,262
THIS PROCESS IS INFLAMMATION 

1437
01:06:57,262 --> 01:06:59,197
MEDIATED SO IT IS THE FOREIGN 

1438
01:06:59,197 --> 01:07:01,132
BODY REACTION.  AND FINALLY TOO 

1439
01:07:01,132 --> 01:07:02,701
MUCH INFLAMMATION CAUSES 

1440
01:07:02,701 --> 01:07:04,602
STENOSIS WHICH IS THE MOST 

1441
01:07:04,602 --> 01:07:05,870
COMMON GRAFT RELATED 

1442
01:07:05,870 --> 01:07:07,105
COMPLICATION AND WE'RE TRYING TO

1443
01:07:07,105 --> 01:07:09,374
DEVELOP BETTER ASSAYS FOR 

1444
01:07:09,374 --> 01:07:11,876
LOOKING AT HOW HOW OUR SEATED 

1445
01:07:11,876 --> 01:07:13,945
SCAFFOLD WILL AL FER THE 

1446
01:07:13,945 --> 01:07:15,613
INFILTRATION WHICH IS WHAT 

1447
01:07:15,613 --> 01:07:17,315
DRIVES THIS TISSUE FORMATION. 

1448
01:07:17,315 --> 01:07:19,951
AND WE'RE DEVELOPING ASSAYS AND 

1449
01:07:19,951 --> 01:07:21,619
EVALUATING PERFORMANCE AS WE 

1450
01:07:21,619 --> 01:07:23,188
SPEAK.  WE RECENTLY COMPLETED 

1451
01:07:23,188 --> 01:07:27,092
THE SAFETY ARMOR OF OUR STUDY 

1452
01:07:27,092 --> 01:07:28,994
AND THE GRAFT HAVE PREVENTATIVE 

1453
01:07:28,994 --> 01:07:32,831
FORMATION OF STENOSIS AWHILE 

1454
01:07:32,831 --> 01:07:35,934
BACK I WROTE A COMMENTARY FOR 

1455
01:07:35,934 --> 01:07:36,568
SCIENCE TRANSLATIONAL MEDICINE 

1456
01:07:36,568 --> 01:07:39,371
TALKING ABOUT THE PROBLEMS OF 

1457
01:07:39,371 --> 01:07:40,538
TRANSLATION TO THE CLINIC AND 

1458
01:07:40,538 --> 01:07:42,507
DECIDED THAT ONE OF THE DRIVING 

1459
01:07:42,507 --> 01:07:44,876
FORCES OF WHAT I CALL THE 

1460
01:07:44,876 --> 01:07:46,378
UNCERTAINTY PRINCIPLE THAT WE'RE

1461
01:07:46,378 --> 01:07:48,980
ALL INTERESTED IN DEVELOPING 

1462
01:07:48,980 --> 01:07:52,384
CUTTING EDGE NEW BIOLOGICS AND 

1463
01:07:52,384 --> 01:07:54,319
DEVICE TO BRING TO THE CLINIC TO

1464
01:07:54,319 --> 01:07:57,055
HELP OUR PATIENTS AND AS SUCH 

1465
01:07:57,055 --> 01:07:58,490
THERE'LL ALWAYS BE A GREAT DEAL 

1466
01:07:58,490 --> 01:08:03,828
OF UNCERTAINTY AND WE COINED THE

1467
01:08:03,828 --> 01:08:05,230
TERM THE BARNEY PHENOMENA AND I 

1468
01:08:05,230 --> 01:08:07,599
THINK MANY OF THE ASSAYS THAT 

1469
01:08:07,599 --> 01:08:09,834
ARE CURRENTLY USED PERHAPS 

1470
01:08:09,834 --> 01:08:11,936
SUFFER FROM THIS BARNY 

1471
01:08:11,936 --> 01:08:15,240
PHENOMENA.  THEY'RE TRIED AND 

1472
01:08:15,240 --> 01:08:21,079
TESTED AND TRUE FROM THE 

1473
01:08:21,079 --> 01:08:21,913
PERSPECTIVE THAT PEOPLE ARE 

1474
01:08:21,913 --> 01:08:23,648
COMFORTABLE USING THEM BUT I 

1475
01:08:23,648 --> 01:08:25,350
WONDER IF WE NEED TO KICK IT UP 

1476
01:08:25,350 --> 01:08:28,186
A NOTCH AND DEVELOP FOR SCIENCE 

1477
01:08:28,186 --> 01:08:29,821
AND APPLY MORE SCIENCE AND I 

1478
01:08:29,821 --> 01:08:32,023
THINK THIS GIVES US THE 

1479
01:08:32,023 --> 01:08:35,827
OPPORTUNITY TO DO THIS I THINK 

1480
01:08:35,827 --> 01:08:37,929
THE PROGRAM IS DOING VERY GOOD 

1481
01:08:37,929 --> 01:08:39,597
SO FAR, IT'S HELPING MY PROJECT 

1482
01:08:39,597 --> 01:08:41,566
QUITE A BIT.  I'M LOOKING 

1483
01:08:41,566 --> 01:08:43,334
FORWARD TO HEARING ABOUT OTHERS'

1484
01:08:43,334 --> 01:08:45,236
WORK BEYOND THE PROJECT I THINK 

1485
01:08:45,236 --> 01:08:46,104
THERE ARE TWO THINGS I'D LIKE TO

1486
01:08:46,104 --> 01:08:48,139
SEE ONE, I THINK I'D LIKE TO SEE

1487
01:08:48,139 --> 01:08:52,744
THE FDA GIVEN THE ABILITY TO 

1488
01:08:52,744 --> 01:08:54,679
WORK WITH INDUSTRY TO FIND 

1489
01:08:54,679 --> 01:08:57,749
MECHANISMS FOR ENHANCING THEIR 

1490
01:08:57,749 --> 01:09:00,151
ABILITY TO SHARE BETTER RELEASE 

1491
01:09:00,151 --> 01:09:01,019
CRITERIA AS THEY'RE DEVELOPED 

1492
01:09:01,019 --> 01:09:05,323
AND SECONDLY, I THINK THAT THE 

1493
01:09:05,323 --> 01:09:09,527
NIH STTR PROGRAMS WOULD BE AN 

1494
01:09:09,527 --> 01:09:11,796
EXCELLENT PLACE TO INTRODUCE 

1495
01:09:11,796 --> 01:09:12,430
ADDITIONAL STUDIES FOCUSED ON 

1496
01:09:12,430 --> 01:09:14,866
THE REGULATORY SCIENCES WHICH 

1497
01:09:14,866 --> 01:09:16,901
ARE FREQUENTLY IGNORED.  THANK 

1498
01:09:16,901 --> 01:09:27,312
YOU FOR YOUR ATTENTION.

1499
01:09:28,213 --> 01:09:32,283
>> RANDALL AND THEN
JOHNNY.  AND

1500
01:09:32,283 --> 01:09:39,824
TELL ME WHEN --

1501
01:09:39,824 --> 01:09:45,096
>> ALL RIGHT.  ON BEHALF
OF MY 

1502
01:09:45,096 --> 01:09:47,132
CO-I I AM PLEASED TO PRESENT 

1503
01:09:47,132 --> 01:09:50,468
WHAT I THINK IS PROBABLY THE 

1504
01:09:50,468 --> 01:09:52,704
SHORTEST FUNDED RMIP AWARD THAT 

1505
01:09:52,704 --> 01:09:54,072
I'VE SEEN YET TODAY.  WE STARTED

1506
01:09:54,072 --> 01:09:56,040
OUR FUNDING ABOUT TWO MONTHS AGO

1507
01:09:56,040 --> 01:09:57,475
SO WE'RE VERY EARLY IN THIS 

1508
01:09:57,475 --> 01:09:59,878
PROCESS.  AND WE'RE WORKING TO 

1509
01:09:59,878 --> 01:10:03,214
DEVELOP SELF THERAPIES TO TREAT 

1510
01:10:03,214 --> 01:10:06,084
DRY MOUTH PARTICULARLY THAT IN 

1511
01:10:06,084 --> 01:10:07,819
THIS PROJECT INDUCED BY 

1512
01:10:07,819 --> 01:10:10,955
RADIATION THERAPY FOR HEAD AND 

1513
01:10:10,955 --> 01:10:15,126
NECK CANCER.  SO REALLY IN TERMS

1514
01:10:15,126 --> 01:10:18,263
OF WHAT ARE THE RMIP FUNDINGS 

1515
01:10:18,263 --> 01:10:20,965
WE'RE FUNDING THROUGH A CLINICAL

1516
01:10:20,965 --> 01:10:22,767
TRIAL PLANNING GRANT.  THIS IS 

1517
01:10:22,767 --> 01:10:24,636
ALLOWING US TO DEVELOP A PHASE 

1518
01:10:24,636 --> 01:10:28,706
ONE STUDY TO TEST THE USE OF 

1519
01:10:28,706 --> 01:10:32,977
AUTOLOGOUS CELLS TO PREVENT 

1520
01:10:32,977 --> 01:10:38,183
DEVELOPMENT OF ROW DAWESED ZERO 

1521
01:10:38,183 --> 01:10:40,885
TOME YA.  THE DATABASES 

1522
01:10:40,885 --> 01:10:42,520
NECESSARY TO RECORD DATA. 

1523
01:10:42,520 --> 01:10:45,456
AND THE FINAL DATA NEEDED FOR 

1524
01:10:45,456 --> 01:10:46,925
IND SUBMISSION AND THIS IS I 

1525
01:10:46,925 --> 01:10:50,495
THINK A REALLY KEY POINT BECAUSE

1526
01:10:50,495 --> 01:10:52,430
SOME OF THE SORT OF VERY SIMPLE 

1527
01:10:52,430 --> 01:10:56,768
STUDIES THAT WE NEED ARE THINGS 

1528
01:10:56,768 --> 01:10:58,369
THAT ARE REALLY CHALLENGING FOR 

1529
01:10:58,369 --> 01:11:02,106
US TO FIND FUNDING FOR.  WE HAVE

1530
01:11:02,106 --> 01:11:06,077
A CURRENT PHASE ONE STUDY THAT 

1531
01:11:06,077 --> 01:11:09,113
IS OPEN AND THAT WAS ALL FUNDED 

1532
01:11:09,113 --> 01:11:11,616
THROUGH SORT OF START-UP FUNDS 

1533
01:11:11,616 --> 01:11:12,350
TO THE INVESTIGATORS BUT THIS 

1534
01:11:12,350 --> 01:11:15,420
IS, YOU KNOW, ALLOWING US TO USE

1535
01:11:15,420 --> 01:11:17,155
PEER-REVIEWED FUNDING TO HELP 

1536
01:11:17,155 --> 01:11:18,923
SUPPORT THIS IND SUBMISSION THAT

1537
01:11:18,923 --> 01:11:21,159
ULTIMATELY WILL OCCUR SORT OF 

1538
01:11:21,159 --> 01:11:24,262
MIDWAY THROUGH OUR FUNDING 

1539
01:11:24,262 --> 01:11:26,264
PERIOD.  FROM OUR POINT OF VIEW,

1540
01:11:26,264 --> 01:11:28,933
SO WE WORK WITH THE WISCONSIN 

1541
01:11:28,933 --> 01:11:29,500
PROGRAM FOR ADVANCED CELL 

1542
01:11:29,500 --> 01:11:31,769
THERAPY AND IN TALKING SORT OF 

1543
01:11:31,769 --> 01:11:32,971
AMONG OUR WORKING GROUP 

1544
01:11:32,971 --> 01:11:34,706
CHALLENGES AND GETTING THERAPIES

1545
01:11:34,706 --> 01:11:37,775
TO PATIENTS IS, YOU KNOW, AS I 

1546
01:11:37,775 --> 01:11:38,810
MENTIONED ONE PRODUCING THIS 

1547
01:11:38,810 --> 01:11:41,379
DATA TO SUPPORT THE IND 

1548
01:11:41,379 --> 01:11:44,415
SUBMISSIONS AND THEN AS WE THINK

1549
01:11:44,415 --> 01:11:47,518
FORWARD WE'RE ALREADY SORT OF IN

1550
01:11:47,518 --> 01:11:51,289
THE INITIAL STEPS FOR OUR NON 

1551
01:11:51,289 --> 01:11:55,260
RMIP STUDY TO THINK OF HOW WE GO

1552
01:11:55,260 --> 01:11:57,228
TO SCALE ONE TO THE STUDIES 

1553
01:11:57,228 --> 01:11:59,330
THAT'S A MAJOR CHALLENGE FOR 

1554
01:11:59,330 --> 01:12:00,531
ULTIMATELY GETTING THESE 

1555
01:12:00,531 --> 01:12:01,699
PATIENT -- OR THESE THERAPIES TO

1556
01:12:01,699 --> 01:12:05,737
AS MANY PATIENTS AS COULD 

1557
01:12:05,737 --> 01:12:08,506
BENEFIT FROM THEM.  SO FUNDING 

1558
01:12:08,506 --> 01:12:10,475
DEDICATED TO PRECLINICAL DATA 

1559
01:12:10,475 --> 01:12:13,778
SUPPORTIVE OF THE IND, USING THE

1560
01:12:13,778 --> 01:12:16,281
IND AS A FINAL SUBMISSION 

1561
01:12:16,281 --> 01:12:17,849
MILESTONE, SOMETHING ON THE 

1562
01:12:17,849 --> 01:12:21,519
ORDER OF R 21 TYPE SIZE AWARDS I

1563
01:12:21,519 --> 01:12:23,788
THINK IS FOR -- AT LEAST FOR OUR

1564
01:12:23,788 --> 01:12:24,889
GROUP HAS PROVED TO BE 

1565
01:12:24,889 --> 01:12:26,791
SUFFICIENT FUNDING TO SORT OF GO

1566
01:12:26,791 --> 01:12:30,428
FROM THE PRECLINICAL DATA TO THE

1567
01:12:30,428 --> 01:12:32,096
IND SUBMISSION.  AND THEN 

1568
01:12:32,096 --> 01:12:34,232
ULTIMATELY, YOU KNOW, LOOKING AT

1569
01:12:34,232 --> 01:12:36,200
THE LATER DEVELOPMENT NIH 

1570
01:12:36,200 --> 01:12:38,369
FUNDING MECHANISMS TO SUPPORT 

1571
01:12:38,369 --> 01:12:41,606
THESE EFFICACY FOCUSED STUDIES. 

1572
01:12:41,606 --> 01:12:43,441
ARE CERTAINLY ONE POSSIBILITY AS

1573
01:12:43,441 --> 01:12:44,776
WAS JUST MENTIONED AND WITH THAT

1574
01:12:44,776 --> 01:12:48,680
I WILL TURN IT BACK TO THE NEXT 

1575
01:12:48,680 --> 01:12:57,255
SPEAKE

1576
01:12:57,255 --> 01:12:57,488
SPEAKER.

1577
01:12:57,488 --> 01:13:02,093
>> JOHNNY AND THEN ASIA
KHAN.  

1578
01:13:02,093 --> 01:13:05,396
THERE YOU GO.

1579
01:13:05,396 --> 01:13:09,300
>> OKAY.  SO, THE GOAL OF
OUR 

1580
01:13:09,300 --> 01:13:11,502
TRIALS THAT WAS FUNDED WAS 

1581
01:13:11,502 --> 01:13:13,371
FUNDED IN 2000 SO WE ARE ON THE 

1582
01:13:13,371 --> 01:13:18,142
END OF THIS.  SO THE GOAL OF 

1583
01:13:18,142 --> 01:13:22,480
THIS WAS TO IMPROVE THE BONE 

1584
01:13:22,480 --> 01:13:25,717
MARROW FOR A PATIENT WITH 

1585
01:13:25,717 --> 01:13:28,219
OSTEOARTHRITIS.  THE TARGET 

1586
01:13:28,219 --> 01:13:33,691
ENROLLMENT, AGAIN, WE HAVE FOR 

1587
01:13:33,691 --> 01:13:37,729
ARM.  WE HAVE BONE MARROW PLUS 

1588
01:13:37,729 --> 01:13:39,597
LOSARTAN AND FIE SE TIN.  WE 

1589
01:13:39,597 --> 01:13:40,631
HAVE ONE HUNDRED PATIENT IN OUR 

1590
01:13:40,631 --> 01:13:43,368
TARGET ENROLLMENT.  25 PER ARM 

1591
01:13:43,368 --> 01:13:45,269
AND I REMEMBER, YOU KNOW, WHEN I

1592
01:13:45,269 --> 01:13:48,306
GOT THIS GRANT FUNDING BY THE 

1593
01:13:48,306 --> 01:13:50,975
NIH, YOU KNOW, FAY CALLED ME AND

1594
01:13:50,975 --> 01:13:52,577
SAID YOU CAN RECRUIT ONE HUNDRED

1595
01:13:52,577 --> 01:13:55,079
PATIENTS AND I SAID, I THINK WE 

1596
01:13:55,079 --> 01:13:55,847
CAN.  

1597
01:13:55,847 --> 01:13:57,448
AND AGAIN I'M VERY HAPPY TO SAY,

1598
01:13:57,448 --> 01:13:58,916
THAT, YOU KNOW, WE HAVE ACHIEVED

1599
01:13:58,916 --> 01:14:00,785
OUR TARGET, YOU KNOW, 

1600
01:14:00,785 --> 01:14:01,586
POPULATION, YOU KNOW, THREE 

1601
01:14:01,586 --> 01:14:05,356
MONTH BEFORE THE DEADLINE 

1602
01:14:05,356 --> 01:14:07,125
DESPITE COVID AND OMICRON SO I 

1603
01:14:07,125 --> 01:14:09,827
THINK WE'RE VERY PROUD OF THIS. 

1604
01:14:09,827 --> 01:14:10,862
AS YOU KNOW CLINICAL TRIAL 

1605
01:14:10,862 --> 01:14:12,530
SOMETIMES THE BIGGEST PROBLEM IS

1606
01:14:12,530 --> 01:14:13,631
WE CANNOT ACHIEVE THE TARGET 

1607
01:14:13,631 --> 01:14:14,599
POPULATION THAT WE NEED WHAT IS 

1608
01:14:14,599 --> 01:14:17,068
THE BIGGEST PROBLEM WE FACE IS 

1609
01:14:17,068 --> 01:14:20,104
REALLY, YOU KNOW, WHEN IT 

1610
01:14:20,104 --> 01:14:21,773
BECOMES TO RECRUITMENT 

1611
01:14:21,773 --> 01:14:25,143
MINORITIES WE TARGET, YOU KNOW, 

1612
01:14:25,143 --> 01:14:26,244
DIFFERENT, YOU KNOW, GENDER MALE

1613
01:14:26,244 --> 01:14:28,045
AND FEMALE.  WE DIDN'T HAVE ANY 

1614
01:14:28,045 --> 01:14:29,213
PROBLEM THERE BUT WHEN IT COMES 

1615
01:14:29,213 --> 01:14:31,616
TO RECRUIT MINORITIES WE HAD TO 

1616
01:14:31,616 --> 01:14:33,217
PUT THE CLINICAL TRIALS ON PAUSE

1617
01:14:33,217 --> 01:14:34,852
TO MAKE SURE THAT WE CAN RECRUIT

1618
01:14:34,852 --> 01:14:38,489
THOSE PATIENT.  AND AGAIN, THAT 

1619
01:14:38,489 --> 01:14:40,725
REQUIRED, YOU KNOW, INTEGRATED 

1620
01:14:40,725 --> 01:14:44,395
WORK WITH THE DSMB, IRB AND 

1621
01:14:44,395 --> 01:14:46,697
HOSPITAL EXECUTIVES AND WHAT WE 

1622
01:14:46,697 --> 01:14:51,035
HAD TO DO WAS TRANSLATE OUR 

1623
01:14:51,035 --> 01:14:53,704
DOCUMENT

1624
01:14:53,704 --> 01:14:55,106
DOCUMENTS IN SPANISH AND MADE 

1625
01:14:55,106 --> 01:14:57,074
SURE WE PUT IT IN THE NEWSPAPER.

1626
01:14:57,074 --> 01:14:59,444
THAT WAS A BIG, YOU KNOW, 

1627
01:14:59,444 --> 01:15:05,516
SETBACK FOR US.  WHAT IS ANOTHER

1628
01:15:05,516 --> 01:15:07,418
TECHNICAL CHALLENGE FOR US IS 

1629
01:15:07,418 --> 01:15:11,923
OUR RMIP STUDY DESIGN WAS AN 

1630
01:15:11,923 --> 01:15:14,592
UNUSUAL COMPLEX WAS COMBINING 

1631
01:15:14,592 --> 01:15:16,461
SAFETY.  BUT ALSO PATIENT 

1632
01:15:16,461 --> 01:15:18,896
REPORTED PAIN AND FUNCTION.  

1633
01:15:18,896 --> 01:15:20,832
WE'RE LOOKING AT EFFICACY OF 

1634
01:15:20,832 --> 01:15:21,699
THOSE TREATMENT AND WE'RE 

1635
01:15:21,699 --> 01:15:23,401
LOOKING AT MECHANISM WE WANTED 

1636
01:15:23,401 --> 01:15:25,837
TO KNOW IF THE CELLS THEMSELVES,

1637
01:15:25,837 --> 01:15:27,205
FIBROSIS CAN PLAY A ROLE THERE 

1638
01:15:27,205 --> 01:15:29,073
BUT I THINK WE BELIEVE THAT, YOU

1639
01:15:29,073 --> 01:15:30,374
KNOW, IT PROVIDE AN OPPORTUNITY 

1640
01:15:30,374 --> 01:15:33,611
FOR INVESTIGATING THE FACTOR 

1641
01:15:33,611 --> 01:15:35,513
ASSOCIATED WITH SUCCESSFUL 

1642
01:15:35,513 --> 01:15:36,547
BIOLOGICAL TREATMENT FOR ALL 

1643
01:15:36,547 --> 01:15:41,486
PATIENT SO WHAT WE NOW  KNOW NOW

1644
01:15:41,486 --> 01:15:43,754
IS WE HAVE MORE IN THE BLOOD 

1645
01:15:43,754 --> 01:15:46,157
THAN PATIENT WITH 

1646
01:15:46,157 --> 01:15:47,024
OSTEOARTHRITIS. 

1647
01:15:47,024 --> 01:15:48,793
AND WE KNOW THAT PATIENT WITH 

1648
01:15:48,793 --> 01:15:52,964
PAIN HAS MORE CELLS THAN PATIENT

1649
01:15:52,964 --> 01:15:55,166
WITHOUT PAIN.  WE KNOW IF WE DO 

1650
01:15:55,166 --> 01:15:57,268
AN MRI OF THE KNEE JOINT WE CAN 

1651
01:15:57,268 --> 01:16:00,004
SEE THAT THE PATIENT THAT HAS A 

1652
01:16:00,004 --> 01:16:03,474
HIGH NUMBER SENESCE SENT CELLS 

1653
01:16:03,474 --> 01:16:06,344
HAS MORE.  AND NOW WE KNOW THE 

1654
01:16:06,344 --> 01:16:10,481
SENESCE SENT CELLS CAN BE FOUND 

1655
01:16:10,481 --> 01:16:12,884
IN BONE MARROW AS WELL AND CAN 

1656
01:16:12,884 --> 01:16:13,951
ALSO BE FOUND IN THE JOINT 

1657
01:16:13,951 --> 01:16:14,185
FLUID. 

1658
01:16:14,185 --> 01:16:15,953
SO I THINK THAT WAS, YOU KNOW, 

1659
01:16:15,953 --> 01:16:17,588
VERY IMPORTANT THING, YOU KNOW, 

1660
01:16:17,588 --> 01:16:19,891
FOR US TO START THIS.  THIS WILL

1661
01:16:19,891 --> 01:16:23,261
BE -- THIS WILL HAVE BEEN 

1662
01:16:23,261 --> 01:16:27,031
IMPOSSIBLE TO DO WITH RN 1 FOR 

1663
01:16:27,031 --> 01:16:28,266
SURE AND MOST SURPRISING THING 

1664
01:16:28,266 --> 01:16:30,334
FOR ME IS WHEN I START THE 

1665
01:16:30,334 --> 01:16:31,536
TRIALS WE WERE HARVESTING THE 

1666
01:16:31,536 --> 01:16:34,472
BONE MARROW.  WE DO THE BONE 

1667
01:16:34,472 --> 01:16:37,875
HARROW -- MARROW CONCENTRATE AND

1668
01:16:37,875 --> 01:16:39,710
WE GET WHAT IS UP INJECTED IN 

1669
01:16:39,710 --> 01:16:42,013
THE PATIENT AND THEN WE GET WHAT

1670
01:16:42,013 --> 01:16:42,613
COME TO THE LAB. 

1671
01:16:42,613 --> 01:16:45,216
AND WHEN I START THE PROJECT I 

1672
01:16:45,216 --> 01:16:46,217
THOUGHT WE WOULD FIND MILLIONS 

1673
01:16:46,217 --> 01:16:47,919
OF STEM CELLS WITHIN THE BONE 

1674
01:16:47,919 --> 01:16:49,453
MARROW OF THE PATIENT BUT IT 

1675
01:16:49,453 --> 01:16:51,255
TURNS OUT THAT WAS NOT MILLIONS 

1676
01:16:51,255 --> 01:16:52,857
OF STEM CELLS, IT WAS THOUSANDS 

1677
01:16:52,857 --> 01:16:54,458
OF STEM CELLS AS YOU CAN SEE 

1678
01:16:54,458 --> 01:16:58,296
HERE, YOU KNOW, THE IS BAR 

1679
01:16:58,296 --> 01:17:00,798
THERE, THAT'S 40 PATIENT WHERE 

1680
01:17:00,798 --> 01:17:01,399
WE HAVE PROBABLY 20,000 STEM 

1681
01:17:01,399 --> 01:17:03,901
CELLS SO CLEARLY IT WAS REALLY 

1682
01:17:03,901 --> 01:17:06,404
IMPORTANT FOR US BECAUSE WE HAVE

1683
01:17:06,404 --> 01:17:08,506
TO SHARE OUR SAMPLE WITH THE 

1684
01:17:08,506 --> 01:17:10,107
CATALYST WHICH IS, YOU KNOW, THE

1685
01:17:10,107 --> 01:17:13,044
PEOPLE THAT LOOK AT THE STEM 

1686
01:17:13,044 --> 01:17:14,946
CELLS IN THE ANALYSIS BUT WHILE 

1687
01:17:14,946 --> 01:17:18,482
WE FIND VERY FEW MSCS, WHEN WE 

1688
01:17:18,482 --> 01:17:22,853
START TO LOOK AT XO SOME WE FIND

1689
01:17:22,853 --> 01:17:23,120
BILLIONS. 

1690
01:17:23,120 --> 01:17:25,356
SO WHAT WE DID IS WE SUBMITTED 

1691
01:17:25,356 --> 01:17:28,426
AN ANCILLARY STUDIES TO START TO

1692
01:17:28,426 --> 01:17:29,760
LOOK AT THE XO SOME IN THOSE 

1693
01:17:29,760 --> 01:17:31,562
PATIENTS BECAUSE WE BELIEVE THAT

1694
01:17:31,562 --> 01:17:36,367
THE EFFECT OF THE COMBINING 

1695
01:17:36,367 --> 01:17:39,270
THESE IS MAYBE RELATED TO THE XO

1696
01:17:39,270 --> 01:17:40,805
SOME NOT REALLY THE STEM CELLS 

1697
01:17:40,805 --> 01:17:42,873
WITHIN THE FRACTION.  AND THIS 

1698
01:17:42,873 --> 01:17:48,980
IS REALLY IMPORTANT FOR US. 

1699
01:17:48,980 --> 01:17:55,319
BECAUSE WE HAVE TO SEND THOSE 

1700
01:17:55,319 --> 01:17:56,520
SAMPLES AND I DON'T WANT TO SEND

1701
01:17:56,520 --> 01:17:59,624
IT TOO EARLY BEFORE WE ANALYZE 

1702
01:17:59,624 --> 01:18:02,426
THE XO SOME WITHIN THIS.  I AM 

1703
01:18:02,426 --> 01:18:04,362
GOING TO CLOSE HERE.  THIS IS 

1704
01:18:04,362 --> 01:18:05,963
CLEARLY A TEAM EFFORT WE 

1705
01:18:05,963 --> 01:18:06,998
WOULDN'T HAVE BEEN ABLE TO DO 

1706
01:18:06,998 --> 01:18:11,369
WITH WITHOUT OUR RMIP FUNDING 

1707
01:18:11,369 --> 01:18:12,303
THIS IS A SIX MILLION DOLLAR 

1708
01:18:12,303 --> 01:18:13,938
CLINICAL TRIAL AND YOU CAN SEE 

1709
01:18:13,938 --> 01:18:15,039
ALL THE PEOPLE THAT PARTICIPATE 

1710
01:18:15,039 --> 01:18:17,241
IN THESE TRIALS HERE AND ALL THE

1711
01:18:17,241 --> 01:18:18,109
ACADEMIC INSTITUTIONS THAT 

1712
01:18:18,109 --> 01:18:19,377
COLLABORATE WITH US, YOU KNOW, 

1713
01:18:19,377 --> 01:18:22,847
IN THIS PROJECT.  THANK YOU VERY

1714
01:18:22,847 --> 01:18:32,957
MUC

1715
01:18:34,558 --> 01:18:34,692
MUCH.

1716
01:18:34,692 --> 01:18:35,926
>> GOOD MORNING, I'M FROM
THE 

1717
01:18:35,926 --> 01:18:37,194
UNIVERSITY OF MIAMI.  THANK YOU 

1718
01:18:37,194 --> 01:18:39,030
SO MUCH, I WANT TO THANK 

1719
01:18:39,030 --> 01:18:41,265
ORGANIZERS WHO HAVE SET IT UP 

1720
01:18:41,265 --> 01:18:45,569
EVERYTHING SO NICELY.  SO I WILL

1721
01:18:45,569 --> 01:18:47,905
BE PRESENTING BASICALLY THIS IS 

1722
01:18:47,905 --> 01:18:50,374
OUR FIRST RMIP GRANT AND MY 

1723
01:18:50,374 --> 01:18:53,611
PRINCIPLE INVESTIGATOR WITH ME. 

1724
01:18:53,611 --> 01:18:56,013
WE ARE BOTH MULTIPLE 

1725
01:18:56,013 --> 01:18:59,083
INVESTIGATORS IS DR. JOSHUA AND 

1726
01:18:59,083 --> 01:19:02,420
HE BASICALLY FOR OUR -- THIS 

1727
01:19:02,420 --> 01:19:03,888
PROJECT WHAT WE ARE DOING WE ARE

1728
01:19:03,888 --> 01:19:06,524
TRYING TO CONFIRM OUR HYPOTHESIS

1729
01:19:06,524 --> 01:19:09,860
AND PERFORMING A PRECLINICAL 

1730
01:19:09,860 --> 01:19:13,297
STUDY TO MAKE SURE OR TO CONFIRM

1731
01:19:13,297 --> 01:19:15,933
THAT THE DELIVERIES OF THE 

1732
01:19:15,933 --> 01:19:18,903
EXOSOMES ARE EXTRACELLULAR 

1733
01:19:18,903 --> 01:19:21,605
VESICLE HELP WITH CARDIAC 

1734
01:19:21,605 --> 01:19:23,407
INDICATION.  SO THERE ARE A FEW.

1735
01:19:23,407 --> 01:19:25,209
WE JUST GOT TWO MONTHS THIS 

1736
01:19:25,209 --> 01:19:27,211
GRANT AND WE'RE VERY NEW TO THIS

1737
01:19:27,211 --> 01:19:30,147
MECHANISM AND WE ARE RIGHT NOW 

1738
01:19:30,147 --> 01:19:31,482
STARTING TO PRODUCE PRODUCTS SO 

1739
01:19:31,482 --> 01:19:32,783
WE CAN DO THESE STUDIES SO 

1740
01:19:32,783 --> 01:19:36,987
THERE'S NOT MUCH DATA FOR US TO 

1741
01:19:36,987 --> 01:19:37,488
PROT

1742
01:19:37,488 --> 01:19:38,756
PRESENT BUT I CAN QUICKLY GO 

1743
01:19:38,756 --> 01:19:41,826
OVER THE TRIAL DESIGN SO WE WANT

1744
01:19:41,826 --> 01:19:43,694
TO -- AT THE UNIVERSITY OF MIAMI

1745
01:19:43,694 --> 01:19:45,196
WE HAVE DONE QUITE A LOT OF WORK

1746
01:19:45,196 --> 01:19:47,898
ON STEM CELLS AND NOW WE ARE 

1747
01:19:47,898 --> 01:19:54,205
MOVING TO APSCS, EXTRACELLULAR 

1748
01:19:54,205 --> 01:19:57,475
VESICLES AND I'M TRYING TO SEE 

1749
01:19:57,475 --> 01:19:59,210
IF SINGLE DOSE VERSUS REPEATED 

1750
01:19:59,210 --> 01:20:01,145
DOSE MAKES A DIFFERENCE AND WE 

1751
01:20:01,145 --> 01:20:03,347
HAVE THREE DIFFERENT COHORT AND 

1752
01:20:03,347 --> 01:20:04,949
ONE HAS SINGLE DOSE WITH SINGLE 

1753
01:20:04,949 --> 01:20:07,451
DOSE OF THREE DIFFERENT DOSES 

1754
01:20:07,451 --> 01:20:08,786
BECAUSE WHEN WE DID OUR 

1755
01:20:08,786 --> 01:20:11,122
PRELIMINARY STUDIES WE TESTED 

1756
01:20:11,122 --> 01:20:13,324
ONE DOSE SO NOW WE HAVE SELECTED

1757
01:20:13,324 --> 01:20:16,861
ONE ABOVE AND ONE BELOW.  SO AND

1758
01:20:16,861 --> 01:20:18,462
THEN THERE IS SECOND COHORT 

1759
01:20:18,462 --> 01:20:21,766
WHERE WE ARE DOING THREE 

1760
01:20:21,766 --> 01:20:22,767
INJECTIONS.  EACH INJECTION IS A

1761
01:20:22,767 --> 01:20:26,871
WEEK APART AND THIS IS ON OUR MY

1762
01:20:26,871 --> 01:20:28,672
MODEL WHICH WE HAVE DEVELOPED 

1763
01:20:28,672 --> 01:20:29,540
THROUGHOUT MANY YEARS AND THEN 

1764
01:20:29,540 --> 01:20:33,310
THE LAST COHORT IS SIX 

1765
01:20:33,310 --> 01:20:34,578
INJECTIONS WEEKLY.  AND THAT 

1766
01:20:34,578 --> 01:20:36,547
IS -- WE'RE DOING THE LOW DOSE, 

1767
01:20:36,547 --> 01:20:40,484
MEDIUM DOSE, HIGH DOSE AND 

1768
01:20:40,484 --> 01:20:41,786
PLACEBO SO IT'S PRETTY 

1769
01:20:41,786 --> 01:20:43,320
ELABORATED STUDY AND WE'RE VERY 

1770
01:20:43,320 --> 01:20:45,389
EXCITED TO START THAT NEXT 

1771
01:20:45,389 --> 01:20:47,024
MONTH.  WE'RE RIGHT NOW IN 

1772
01:20:47,024 --> 01:20:50,895
PROCESS OF MAKING EXOSOMES OR 

1773
01:20:50,895 --> 01:20:52,530
EXTRACELLULAR VESICLES SINCE WE 

1774
01:20:52,530 --> 01:20:54,165
HAVE NOT STARTED OUR PROJECT.  

1775
01:20:54,165 --> 01:20:57,067
SO I AM MORE LIKE, YOU KNOW, THE

1776
01:20:57,067 --> 01:20:58,903
CHALLENGE I CAN SEE I WILL BE 

1777
01:20:58,903 --> 01:21:03,374
FACING IS TRANSLATING IT TO 

1778
01:21:03,374 --> 01:21:09,213
LARGE ANIMAL BECAUSE THIS IS 

1779
01:21:09,213 --> 01:21:11,982
SMALL ANIMAL STUDY.  I HOPE 

1780
01:21:11,982 --> 01:21:15,920
THERE'S MORE FUNDING MECHANISM 

1781
01:21:15,920 --> 01:21:19,056
WHERE WE CAN SUPPORT THOSE LARGE

1782
01:21:19,056 --> 01:21:20,758
ANIMAL TRIALS AND WE ARE FOCUSED

1783
01:21:20,758 --> 01:21:23,861
ON THE INDICATION.  WE HAVE THE 

1784
01:21:23,861 --> 01:21:27,865
SMALL WORK ON MNRI AND THERE MAY

1785
01:21:27,865 --> 01:21:29,600
BE PROBLEM TRANSLATING TO OTHER 

1786
01:21:29,600 --> 01:21:30,367
DISEASES.  RIGHT NOW WE'RE 

1787
01:21:30,367 --> 01:21:33,871
WORKING ON THE MODEL.  SO I 

1788
01:21:33,871 --> 01:21:35,706
BELIEVE AND THINK THAT I HAVE TO

1789
01:21:35,706 --> 01:21:38,108
GO BACK AND DO SOME SMALL ANIMAL

1790
01:21:38,108 --> 01:21:41,512
AND LARGE ANIMAL WORK WITH, YOU 

1791
01:21:41,512 --> 01:21:45,416
KNOW, THIS PRODUCT.  SO 

1792
01:21:45,416 --> 01:21:46,784
HOPEFULLY WE WILL PASS THESE 

1793
01:21:46,784 --> 01:21:48,085
CHALLENGES OR OVERCOME WHEN WE 

1794
01:21:48,085 --> 01:21:51,689
GET THERE.  IN GENERAL TERM THAT

1795
01:21:51,689 --> 01:21:54,225
WHAT I FEEL THAT THERE'S A 

1796
01:21:54,225 --> 01:21:56,627
REGULATORY HURDLE HERE.  I -- 

1797
01:21:56,627 --> 01:21:59,463
THE FDA FOLKS ARE HERE SO I CAN 

1798
01:21:59,463 --> 01:22:02,132
PROBABLY, YOU KNOW, TALK ABOUT 

1799
01:22:02,132 --> 01:22:03,667
THAT.  THAT REGULATORY PATHWAY 

1800
01:22:03,667 --> 01:22:05,336
FOR BRINGING REGENERATIVE 

1801
01:22:05,336 --> 01:22:08,706
THERAPY TO MAKE IT IS COMPLEX 

1802
01:22:08,706 --> 01:22:12,576
AND IT VERY SIGNIFICANTLY ACROSS

1803
01:22:12,576 --> 01:22:13,510
DIFFERENT REGIONS. 

1804
01:22:13,510 --> 01:22:17,181
THESE ARE COMPLEX AND, YOU KNOW,

1805
01:22:17,181 --> 01:22:19,183
DURING WHEN PEOPLE ARE EDGE -- 

1806
01:22:19,183 --> 01:22:22,419
GETTING THEIR EDUCATION I FEEL 

1807
01:22:22,419 --> 01:22:25,656
THAT THERE SHOULD BE SOME -- IN 

1808
01:22:25,656 --> 01:22:27,791
MODIFICATION OR CHANGES IN 

1809
01:22:27,791 --> 01:22:29,426
CURRICULUM THAT PHYSICIANS OR 

1810
01:22:29,426 --> 01:22:31,161
PH.D.S, THEY ARE EDUCATED ON 

1811
01:22:31,161 --> 01:22:32,596
THESE REGULATIONS.  AND THEY 

1812
01:22:32,596 --> 01:22:34,298
KNOW WHAT THEY WILL BE DEALING 

1813
01:22:34,298 --> 01:22:35,332
WITH WHEN THEY HAVE A THERAPY 

1814
01:22:35,332 --> 01:22:38,836
WHICH THEY WILL TAKE IT FROM, 

1815
01:22:38,836 --> 01:22:41,605
YOU KNOW, BENCH TO BEDSIDE AND 

1816
01:22:41,605 --> 01:22:42,473
ALSO THE STRINGENT REQUIREMENT 

1817
01:22:42,473 --> 01:22:45,142
FOR SAFETY AND EFFICACY ARE 

1818
01:22:45,142 --> 01:22:46,477
ESSENTIAL BUT CAN BE A BARRIER 

1819
01:22:46,477 --> 01:22:49,980
TO INNOVATION AND TIMELY PATIENT

1820
01:22:49,980 --> 01:22:52,383
ACCESS.  SO AND ALSO THIS IS 

1821
01:22:52,383 --> 01:22:56,854
LIKE, YOU KNOW, NAVIGATING THE 

1822
01:22:56,854 --> 01:22:58,622
EVOLVING AND GUIDELINES OR 

1823
01:22:58,622 --> 01:23:00,424
REGULATIONS IS ALSO A CHALLENGE 

1824
01:23:00,424 --> 01:23:02,459
AND ALSO THE HARMONIZATION OF 

1825
01:23:02,459 --> 01:23:03,994
THESE REGULATORY STANDARDS WHICH

1826
01:23:03,994 --> 01:23:06,230
THERE'S A LOT OF EFFORTS DONE IN

1827
01:23:06,230 --> 01:23:11,669
THAT AREA BUT I FEEL IF WE CAN 

1828
01:23:11,669 --> 01:23:13,504
HAVE INITIATIVE WHERE THESE 

1829
01:23:13,504 --> 01:23:15,839
BIOMARKERS AND PREDICTIVE 

1830
01:23:15,839 --> 01:23:17,207
TESTINGS AND PATIENT REPORTED 

1831
01:23:17,207 --> 01:23:19,176
OUTCOMES CAN BE MORE 

1832
01:23:19,176 --> 01:23:20,044
COMMUNICATED THAT WOULD BE 

1833
01:23:20,044 --> 01:23:22,379
REALLY HELPFUL.  I WILL QUICKLY 

1834
01:23:22,379 --> 01:23:26,483
GO TO THE SLIDE.  IT'S MORE 

1835
01:23:26,483 --> 01:23:28,552
DISCUSSING ABOUT THE REGULATORY 

1836
01:23:28,552 --> 01:23:29,853
SCIENCE, THERE'S THE GAP WHICH I

1837
01:23:29,853 --> 01:23:31,455
ALREADY MENTIONED BUT THERE IS 

1838
01:23:31,455 --> 01:23:33,857
ONE THING I WANTED TO MENTION 

1839
01:23:33,857 --> 01:23:35,893
WHICH IS MY MAIN AREA IS WHEN A 

1840
01:23:35,893 --> 01:23:37,294
PRODUCT IS DEVELOPED, A THERAPY 

1841
01:23:37,294 --> 01:23:39,063
IS DEVELOPED, MAKING THAT 

1842
01:23:39,063 --> 01:23:40,364
PRODUCT, SCALING UP THAT 

1843
01:23:40,364 --> 01:23:42,132
PRODUCT, CHARACTERIZING THAT 

1844
01:23:42,132 --> 01:23:43,867
PRODUCT, MOST OF US FEEL OR 

1845
01:23:43,867 --> 01:23:45,970
THINK THAT WHEN YOUR PRODUCT IS 

1846
01:23:45,970 --> 01:23:48,472
DEVELOPED AND YOU ARE DOING 

1847
01:23:48,472 --> 01:23:50,074
CLINICAL TRIAL IT STARTS THERE 

1848
01:23:50,074 --> 01:23:52,009
AND I'M SURE THERE IS AN ONGOING

1849
01:23:52,009 --> 01:23:55,312
CHALLENGE OF SCALING UP.  FULLY 

1850
01:23:55,312 --> 01:23:57,481
CHARACTERIZING YOUR PRODUCT AND 

1851
01:23:57,481 --> 01:23:59,650
CHALLENGING THOSE ONGOING THINGS

1852
01:23:59,650 --> 01:24:00,484
WHICH WE DON'T KNOW SOMETIMES 

1853
01:24:00,484 --> 01:24:03,487
ESTABLISHING A POTENCY ASSAY AND

1854
01:24:03,487 --> 01:24:06,223
IF YOUR MODE OF MECHANISM IS NOT

1855
01:24:06,223 --> 01:24:08,659
WELL-DEFINED OR YOU'RE DEFINING 

1856
01:24:08,659 --> 01:24:10,561
IT, ESTABLISHING THOSE ASSAYS IS

1857
01:24:10,561 --> 01:24:12,629
DIFFICULT SO WITH THE HELP OF 

1858
01:24:12,629 --> 01:24:15,666
THESE FUNDING INITIATIVE I FEEL 

1859
01:24:15,666 --> 01:24:17,634
THAT THERE SHOULD BE SOME FOCUS 

1860
01:24:17,634 --> 01:24:19,136
ON PRODUCTS WHICH ARE ALREADY 

1861
01:24:19,136 --> 01:24:21,305
DEVELOPED AND WE HAVE TO 

1862
01:24:21,305 --> 01:24:25,542
MAINTAIN IT OR GO WITH THE 

1863
01:24:25,542 --> 01:24:31,815
SCALING UP AND EDUCATION 

1864
01:24:31,815 --> 01:24:32,850
DEFINITELY.  WE NEED TO TRAIN 

1865
01:24:32,850 --> 01:24:34,518
PEOPLE LIKE US AND RESEARCHERS 

1866
01:24:34,518 --> 01:24:35,919
THAT WHAT ARE THESE STEPS THEY 

1867
01:24:35,919 --> 01:24:38,689
HAVE TO TAKE IF THEY WANT TO 

1868
01:24:38,689 --> 01:24:40,858
TAKE A THERAPY FROM THE BENCH TO

1869
01:24:40,858 --> 01:24:47,131
BED SITE -- SIDE.  THIS 

1870
01:24:47,131 --> 01:24:49,633
CONCLUDES MY COMMENTS.  THANK 

1871
01:24:49,633 --> 01:24:50,267
YOU, EVERYBODY.

1872
01:24:50,267 --> 01:24:54,471
>> I'M AMAZED.  THANK YOU,
ALL, 

1873
01:24:54,471 --> 01:24:57,708
FOR DOING SO WELL.  AND STICKING

1874
01:24:57,708 --> 01:25:00,010
TO THE SHORT TALK FORMAT.  WE 

1875
01:25:00,010 --> 01:25:03,947
SURE HEARD A LOT.  AND I THINK, 

1876
01:25:03,947 --> 01:25:05,716
YOU KNOW, THERE'S ABUNDANT FOOD 

1877
01:25:05,716 --> 01:25:10,487
FOR THOUGHT HERE.  WE WILL -- 

1878
01:25:10,487 --> 01:25:14,091
THIS WILL GROW IF FAY, WON'T YOU

1879
01:25:14,091 --> 01:25:16,527
COME ON UP.  SO I THINK ONE 

1880
01:25:16,527 --> 01:25:18,729
THING WE CAN START TO DO OVER 

1881
01:25:18,729 --> 01:25:20,798
THE COURSE OF TODAY IS TO 

1882
01:25:20,798 --> 01:25:23,934
IDENTIFY THEMES THAT WE HEAR.  

1883
01:25:23,934 --> 01:25:27,337
AND I THINK THIS -- IT ISN'T 

1884
01:25:27,337 --> 01:25:29,973
ROCKET SCIENCE.  IT'S STEPPING 

1885
01:25:29,973 --> 01:25:33,777
BACK AND LISTENING AND TRYING TO

1886
01:25:33,777 --> 01:25:35,279
UNDERSTAND SORT OF COMMON THEMES

1887
01:25:35,279 --> 01:25:38,515
THAT COME UP ACROSS THE TALKS.  

1888
01:25:38,515 --> 01:25:41,752
AND BECAUSE WE HAVE SOME TIME I 

1889
01:25:41,752 --> 01:25:44,688
THINK WE CAN START NOW IS THERE 

1890
01:25:44,688 --> 01:25:47,658
ANY QUESTIONS FOR THE SPEAKERS? 

1891
01:25:47,658 --> 01:25:51,095
I THINK JANUARY  JANNA, WE'RE 

1892
01:25:51,095 --> 01:25:53,130
GOING TO NEED A MICROPHONE. 

1893
01:25:53,130 --> 01:25:54,998
SO JANNA WILL HAVE THE 

1894
01:25:54,998 --> 01:26:01,171
MICROPHONE.  JANNA, WE'RE GOING 

1895
01:26:01,171 --> 01:26:01,605
NEED A MICROPHONE. 

1896
01:26:01,605 --> 01:26:02,106
SO JANNA WILL HAVE THE 

1897
01:26:02,106 --> 01:26:02,773
MICROPHONE. JANNA, WE'RE GOING  

1898
01:26:02,773 --> 01:26:03,207
NEED A MICROPHONE. 

1899
01:26:03,207 --> 01:26:03,707
SO JANNA WILL HAVE THE 

1900
01:26:03,707 --> 01:26:06,043
MICROPHONE.  SHOULD I START WITH

1901
01:26:06,043 --> 01:26:06,677
THE THEMES WE HEARD?

1902
01:26:06,677 --> 01:26:17,154
>> (SPEAKER FAR FROM MIC).

1903
01:26:26,263 --> 01:26:29,766
>> WE ARE BEING VIDEO
CAST.

1904
01:26:29,766 --> 01:26:31,401
>> I HAVE A QUESTION FOR 

1905
01:26:31,401 --> 01:26:33,036
DR. STERN, I WAS WONDERING IF HE

1906
01:26:33,036 --> 01:26:37,174
COULD ELABORATE ON THE EARLY FDA

1907
01:26:37,174 --> 01:26:39,576
OPPORTUNITIES.  HE MENTIONED 

1908
01:26:39,576 --> 01:26:49,853
SOME PROGRAMS.

1909
01:26:54,224 --> 01:26:58,495
>> WE'RE LOOKING TO MOVE A
CR

1910
01:26:58,495 --> 01:27:00,964
CRYOPRESERVATION TECHNIQUE AND 

1911
01:27:00,964 --> 01:27:03,967
THE PATHWAY TO GET FEEDBACK FROM

1912
01:27:03,967 --> 01:27:10,440
THE FDA EARLY ON IS LIMITED.  

1913
01:27:10,440 --> 01:27:18,682
SO, I'M SORRY, THIS REQUIRES A 

1914
01:27:18,682 --> 01:27:20,150
FAIRLY MATURE APPLICATION TO 

1915
01:27:20,150 --> 01:27:22,119
REQUEST MEETINGS WITH THE FDA 

1916
01:27:22,119 --> 01:27:24,821
AND THERE ARE TWO NEW PROGRAMS 

1917
01:27:24,821 --> 01:27:26,490
THAT THE CAT WHICH I HAVEN'T 

1918
01:27:26,490 --> 01:27:28,358
FIGURED OUT HOW TO ACCESS WHICH 

1919
01:27:28,358 --> 01:27:30,494
THERE CAN BE A DISCUSSION WITH 

1920
01:27:30,494 --> 01:27:32,696
THE FDA EARLY ON, LESS FORMAL 

1921
01:27:32,696 --> 01:27:36,133
PATHWAYS AND REALLY BY RAISING 

1922
01:27:36,133 --> 01:27:39,703
THOSE TO THE RMIP PROGRAM WAS 

1923
01:27:39,703 --> 01:27:42,639
INITIALLY NIH AND FDA AND HOW DO

1924
01:27:42,639 --> 01:27:48,178
WE ENGAGE THE FDA MORE 

1925
01:27:48,178 --> 01:27:51,114
EXTENSIVELY AND PERHAPS LESS 

1926
01:27:51,114 --> 01:27:52,449
FORMALLY WOULD BE VERY 

1927
01:27:52,449 --> 01:27:53,884
ADVANTAGEOUS TO OUR EFFORTS AT 

1928
01:27:53,884 --> 01:27:54,084
LEAST.

1929
01:27:54,084 --> 01:27:56,053
>> SO I THINK WE HEARD
THAT 

1930
01:27:56,053 --> 01:27:58,822
CERTAINLY WAS A THEME THAT CAME 

1931
01:27:58,822 --> 01:27:59,990
UP.  THERE ARE TWO WAYS -- 

1932
01:27:59,990 --> 01:28:01,825
MULTIPLE WAYS TO THINK ABOUT IT.

1933
01:28:01,825 --> 01:28:04,194
ONE IS CONVERSATIONS WITH THE 

1934
01:28:04,194 --> 01:28:06,830
FDA.  AND LISTENING TO THIS AND 

1935
01:28:06,830 --> 01:28:09,866
OTHER WORKSHOPS THE WAY I WOULD 

1936
01:28:09,866 --> 01:28:11,401
FORMULATE IT IS, WHAT IS THE 

1937
01:28:11,401 --> 01:28:14,304
DATA THAT WE NEED TO HELP THE 

1938
01:28:14,304 --> 01:28:17,708
FDA MAKE DECISIONS?  AND AS 

1939
01:28:17,708 --> 01:28:20,777
SOMEONE ELSE -- AS YOU ACTUALLY 

1940
01:28:20,777 --> 01:28:23,046
SAID, WE -- WITH THE CELL 

1941
01:28:23,046 --> 01:28:24,214
CHARACTERIZATION WE'RE LEARNING 

1942
01:28:24,214 --> 01:28:27,117
A LOT ABOUT WHAT'S IN THESE 

1943
01:28:27,117 --> 01:28:29,152
PREPS AND IT'S SOMETIMES 

1944
01:28:29,152 --> 01:28:30,821
SURPRISING AND SOMEONE ELSE SAID

1945
01:28:30,821 --> 01:28:31,922
THERE WERE CELLS IN THEIR PREP 

1946
01:28:31,922 --> 01:28:33,390
THAT WAS IDENTIFIED.  SO YOU CAN

1947
01:28:33,390 --> 01:28:36,627
SEE HOW THAT CAN GIVE THE FDA A 

1948
01:28:36,627 --> 01:28:39,329
LITTLE PAUSE AS TO OKAY WHAT, IS

1949
01:28:39,329 --> 01:28:41,531
IT?  WHAT'S THE DATA?  WHAT IS 

1950
01:28:41,531 --> 01:28:43,166
IT THAT WE COULD DO SOME 

1951
01:28:43,166 --> 01:28:44,668
EXPERIMENTS THAT MAY HAVE 

1952
01:28:44,668 --> 01:28:49,172
SPECIFIC GOALS BUT THAT WOULD 

1953
01:28:49,172 --> 01:28:51,441
GENERATE DATA THAT WOULD HELP 

1954
01:28:51,441 --> 01:28:52,909
THE FDA UNDERSTAND WHAT SAFETY 

1955
01:28:52,909 --> 01:28:54,278
MEANS AND YOU CAN TALK ABOUT IN 

1956
01:28:54,278 --> 01:28:56,847
THE ANIMAL MODEL STAGE, YOU CAN 

1957
01:28:56,847 --> 01:29:01,151
TALK AT THE INITIAL, YOU KNOW, 

1958
01:29:01,151 --> 01:29:04,221
WHAT ARE YOU GOING GIVE TO THE 

1959
01:29:04,221 --> 01:29:05,355
HUMANS AND THEN SCALE UP AND 

1960
01:29:05,355 --> 01:29:07,991
THEN IT GOES TO THE RELATED 

1961
01:29:07,991 --> 01:29:09,893
QUESTION OF QUALITY CONTROL.  

1962
01:29:09,893 --> 01:29:12,362
THAT WITH THE GENERATION OF THE 

1963
01:29:12,362 --> 01:29:16,199
AUTOMATED SYSTEMS, FOR PRODUCING

1964
01:29:16,199 --> 01:29:19,970
CELLS, AND CLOSED CIRCUIT 

1965
01:29:19,970 --> 01:29:21,305
SYSTEMS, I THINK THAT IS GOING 

1966
01:29:21,305 --> 01:29:23,707
TO STREAMLINE A LOT OF THE 

1967
01:29:23,707 --> 01:29:25,876
PRODUCTION PROCESS AT EACH 

1968
01:29:25,876 --> 01:29:27,744
STAGE.  BUT THERE'S STILL THE 

1969
01:29:27,744 --> 01:29:29,179
SAME QUESTION.  WHAT ARE YOU 

1970
01:29:29,179 --> 01:29:31,348
GIVING?  WHAT'S IN THE PREP?  IS

1971
01:29:31,348 --> 01:29:34,318
IT SAFE AND IS IT EFFECTIVE?  SO

1972
01:29:34,318 --> 01:29:37,354
HOW CAN WE GENERATE DATA USING 

1973
01:29:37,354 --> 01:29:39,022
INDIVIDUAL PROJECTS WITH THE 

1974
01:29:39,022 --> 01:29:41,425
SPECIFIC MISSIONS TO GENERATE 

1975
01:29:41,425 --> 01:29:46,496
DATA AS TO WHAT IS SAFE AND 

1976
01:29:46,496 --> 01:29:48,398
EFFECTIVE?  I THINK -- THIS IS 

1977
01:29:48,398 --> 01:29:51,201
ONE WAY -- THAT'S A THEME THAT I

1978
01:29:51,201 --> 01:29:55,806
THINK I HEARD TODAY.  ANY 

1979
01:29:55,806 --> 01:29:59,409
COMMENTS? TONY, I'M SORRY -- 

1980
01:29:59,409 --> 01:30:07,184
TONY AND -- TONY AND THEN DAN.

1981
01:30:07,184 --> 01:30:09,152
>> I WILL BE SPEAKING FOR
THE 

1982
01:30:09,152 --> 01:30:10,887
ISCT A LITTLE BIT LATER BUT I 

1983
01:30:10,887 --> 01:30:13,390
THINK ONE OF THE COMMON THEMES 

1984
01:30:13,390 --> 01:30:15,792
WE'VE HEARD IN ADDITION TO THE 

1985
01:30:15,792 --> 01:30:17,661
MANUFACTURING REGULATORY IS 

1986
01:30:17,661 --> 01:30:19,162
POTENCY.  ALL RIGHT, THIS CAME 

1987
01:30:19,162 --> 01:30:21,898
UP A COUPLE TIMES AND A COUPLE 

1988
01:30:21,898 --> 01:30:25,035
OF THE EXAMPLES WERE THAT YOU 

1989
01:30:25,035 --> 01:30:28,338
CAN DO TRIAL DIFFERENTIATION OR 

1990
01:30:28,338 --> 01:30:30,874
CHARACTERIZE YOUR EMBRYONIC 

1991
01:30:30,874 --> 01:30:34,010
MARKERS OR THINGS LIKE THAT.  

1992
01:30:34,010 --> 01:30:36,646
IT'S POTENCY AND PATIENT 

1993
01:30:36,646 --> 01:30:39,149
PHENOTYPE.  NOT EVERY PATIENT IS

1994
01:30:39,149 --> 01:30:42,686
THE SAME REGARDLESS OF THE 

1995
01:30:42,686 --> 01:30:44,321
DISEASE.  I THINK WE'RE THE SAME

1996
01:30:44,321 --> 01:30:45,522
WHERE WE CAN BE REALLY HELPFUL 

1997
01:30:45,522 --> 01:30:47,457
IN SUPPORTING THE TYPES OF 

1998
01:30:47,457 --> 01:30:50,927
STUDIES THAT WOULD DEFINE 

1999
01:30:50,927 --> 01:30:53,196
POTENCY.  AND ALONG WITH POTENCY

2000
01:30:53,196 --> 01:30:55,132
IS MECHANISMS OF ACTION BECAUSE 

2001
01:30:55,132 --> 01:30:56,433
THEY'RE HAND IN HAND FOR 

2002
01:30:56,433 --> 01:30:57,467
DIFFERENT DISEASES YOU CAN HAVE 

2003
01:30:57,467 --> 01:30:59,302
THE SAME CELL APPLIED OR THE 

2004
01:30:59,302 --> 01:31:01,838
SAME CELL TYPE APPLIED ACROSS 

2005
01:31:01,838 --> 01:31:03,206
THE SPECTRUM DIFFERENT 

2006
01:31:03,206 --> 01:31:04,941
INDICATIONS AND IT'S GOING TO 

2007
01:31:04,941 --> 01:31:10,180
WORK DIFFERENTLY.  AND USE MSCS 

2008
01:31:10,180 --> 01:31:12,582
THEY ALL CHANGE THEIR PHENOTYPE 

2009
01:31:12,582 --> 01:31:14,418
DEPENDING ON THE INFLAMMATORY 

2010
01:31:14,418 --> 01:31:19,656
ENVIRONMENT THEY ENCOUNTER 

2011
01:31:19,656 --> 01:31:22,259
INVIVO YOU CAN CHARACTERIZE THEM

2012
01:31:22,259 --> 01:31:22,993
BUT THAT'S NOT REAL LIFE TO 

2013
01:31:22,993 --> 01:31:25,162
SUPPORT STUDIES THAT WOULD 

2014
01:31:25,162 --> 01:31:27,531
ADDRESS POTENCY, PATIENT 

2015
01:31:27,531 --> 01:31:28,698
PHENOTYPE, WHAT REALLY HAPPEN TO

2016
01:31:28,698 --> 01:31:31,535
THE CELL OR CELLS ONCE THEY SEE,

2017
01:31:31,535 --> 01:31:32,736
AGAIN, THE CLINICAL ENVIRONMENT,

2018
01:31:32,736 --> 01:31:34,438
I THINK WOULD GO A LONG WAY AND 

2019
01:31:34,438 --> 01:31:36,473
IT ALSO ADDRESSES IN PART THE 

2020
01:31:36,473 --> 01:31:39,342
FACT THAT A LOT OF THINGS WORK 

2021
01:31:39,342 --> 01:31:41,077
IN -- AND THIS CAME UP 

2022
01:31:41,077 --> 01:31:43,747
REPEATEDLY THE MOUSE STATE YOUR 

2023
01:31:43,747 --> 01:31:45,816
NAME FOR THE RECORD  STUDIES 

2024
01:31:45,816 --> 01:31:49,853
THAT JUST DON'T FLY IN PATIENTS.

2025
01:31:49,853 --> 01:31:52,789
THAT WOULD BE A GOOD USE OF OUR 

2026
01:31:52,789 --> 01:31:53,957
THINKING AND FUNDING.

2027
01:31:53,957 --> 01:31:57,561
>> THAT'S EXCELLENT, TONY.

2028
01:31:57,561 --> 01:31:59,930
>> THANKS.  HI, TONY.  I
JUST 

2029
01:31:59,930 --> 01:32:02,165
WANTED TO ECHO WHAT JEFFREY AND 

2030
01:32:02,165 --> 01:32:04,501
DAN SAID ABOUT POTENCY ASSAYS 

2031
01:32:04,501 --> 01:32:08,705
AND ALSO DAN'S POINT ABOUT 

2032
01:32:08,705 --> 01:32:10,740
EPIGENETICS TRAJECTORY ANALYSIS 

2033
01:32:10,740 --> 01:32:13,109
AND SINGLE CELL ANALYSIS THAT IS

2034
01:32:13,109 --> 01:32:14,511
A COMMON ELLE TOOLE FOR EVERY 

2035
01:32:14,511 --> 01:32:17,214
CELL LINEAGE THAT IS A COMMON 

2036
01:32:17,214 --> 01:32:19,349
GRAMMAR THAT CAN BE USED TO 

2037
01:32:19,349 --> 01:32:21,017
STUDY DIFFERENT CELL STATES.  

2038
01:32:21,017 --> 01:32:22,385
ACROSS DIFFERENT TISSUE TYPES.  

2039
01:32:22,385 --> 01:32:24,387
AND SO WE MIGHT THINK ABOUT THAT

2040
01:32:24,387 --> 01:32:26,923
AS -- IN TERMS OF IN PROCESS 

2041
01:32:26,923 --> 01:32:29,559
MILE MARKERS, POTENCY ASSAYS 

2042
01:32:29,559 --> 01:32:31,661
BECAUSE WE KNOW THOSE ARE 

2043
01:32:31,661 --> 01:32:35,866
CORRELATED WITH PHENOTYPES WITH 

2044
01:32:35,866 --> 01:32:38,401
THAT AND SAYING DIFFERENT KINDS 

2045
01:32:38,401 --> 01:32:41,738
OF POTENCY ASSAYS AND DIFFERENT 

2046
01:32:41,738 --> 01:32:45,375
TRAJECTORIES FOR TISSUES.

2047
01:32:45,375 --> 01:32:49,379
>> ANYONE ELSE?  SO I --
ECHO 

2048
01:32:49,379 --> 01:32:51,047
WHAT BOB SAID.  WHAT KIND OF 

2049
01:32:51,047 --> 01:32:53,149
DATA WE CAN, YOU KNOW, PROVIDE 

2050
01:32:53,149 --> 01:32:54,718
FOR FDA BECAUSE -- AT LEAST IN 

2051
01:32:54,718 --> 01:32:57,587
MY CONVERSATION WITH OUR FDA 

2052
01:32:57,587 --> 01:32:58,555
COLLEAGUES, IF YOU LISTEN TO 

2053
01:32:58,555 --> 01:33:02,125
ENOUGH FDA TALKS, THEY ACTUALLY 

2054
01:33:02,125 --> 01:33:05,929
VERY OPEN FOR DISCUSSION.  AND 

2055
01:33:05,929 --> 01:33:07,731
THERE'S NO -- ONE PATHWAY.  I 

2056
01:33:07,731 --> 01:33:12,669
THINK FOR THEM, SAFETY IS VERY 

2057
01:33:12,669 --> 01:33:13,737
CENTRIC.  RIGHT?  SO IF YOU 

2058
01:33:13,737 --> 01:33:19,175
ARE -- OR YOUR COLLEAGUES ARE 

2059
01:33:19,175 --> 01:33:21,278
THE FDA ADVISORY BOARD THESE ARE

2060
01:33:21,278 --> 01:33:23,213
THE PLACES YOU CAN PUT IN YOUR 

2061
01:33:23,213 --> 01:33:26,283
IDEAS AND WHAT CAN YOU OFFER TO 

2062
01:33:26,283 --> 01:33:29,052
ENSURE WHAT THEY ARE LOOKING 

2063
01:33:29,052 --> 01:33:32,622
FOR?  SO I AGREE WITH THE ENGAGE

2064
01:33:32,622 --> 01:33:35,425
WITH THE FDA EARLY BUT 

2065
01:33:35,425 --> 01:33:37,961
OFTENTIMES, THEY DON'T GIVE 

2066
01:33:37,961 --> 01:33:39,195
PRE-APPROVAL EVEN IF THEY ARE 

2067
01:33:39,195 --> 01:33:40,664
ENGAGING EARLY.  SOMETIMES THEY 

2068
01:33:40,664 --> 01:33:44,134
MIGHT PUT THEM INTO CONFLICT.  

2069
01:33:44,134 --> 01:33:54,344
SO YEAH.  DAN, GO AHEAD.

2070
01:33:54,344 --> 01:33:55,845
>> SO ACKNOWLEDGING THAT,
THE 

2071
01:33:55,845 --> 01:33:58,648
FDA HAS COME BACK NOW REPEATEDLY

2072
01:33:58,648 --> 01:33:59,716
WITH RESPECT TO CLINICAL 

2073
01:33:59,716 --> 01:34:06,056
INVESTIGATIONS FOR THE MSCS AND 

2074
01:34:06,056 --> 01:34:07,057
WHAT THEY SPECIFICALLY ASK FOR 

2075
01:34:07,057 --> 01:34:08,858
ARE POTENCY ASSAYS.  HOW DO YOU 

2076
01:34:08,858 --> 01:34:12,195
DEFINE YOUR POTENCY.  SO I THINK

2077
01:34:12,195 --> 01:34:13,763
AGAIN WHAT INFORMATION CAN WE 

2078
01:34:13,763 --> 01:34:15,999
PROVIDE IF WE CAN DESIGN A 

2079
01:34:15,999 --> 01:34:18,735
CONSORTIUM APPROACH THAT WOULD 

2080
01:34:18,735 --> 01:34:20,303
ADDRESS AMONGST EVERYTHING ELSE 

2081
01:34:20,303 --> 01:34:22,072
MECHANISMS AND POTENCY.  THAT'S 

2082
01:34:22,072 --> 01:34:31,047
WHAT THE FDA WANTS.

2083
01:34:31,047 --> 01:34:40,857
>> YEAH.  THANK YOU.

2084
01:34:40,857 --> 01:34:44,227
>> HI, CHRIS.  I THINK A
LOT OF 

2085
01:34:44,227 --> 01:34:45,562
PEOPLE HERE ARE COMING FROM 

2086
01:34:45,562 --> 01:34:47,197
ACADEMIA AND THIS IS REALLY 

2087
01:34:47,197 --> 01:34:48,431
INDUSTRY.  I DON'T THINK WE'RE 

2088
01:34:48,431 --> 01:34:52,936
AT ALL FAMILIAR DEALING WITH 

2089
01:34:52,936 --> 01:34:53,903
PROPRIETARY INFORMATION AND IT'S

2090
01:34:53,903 --> 01:34:54,904
NOT THE WAY WE'RE TRAINED BUT 

2091
01:34:54,904 --> 01:34:56,172
YOU HAVE TO LEARN HOW TO DO IT 

2092
01:34:56,172 --> 01:34:57,574
IF YOU WANT TO GET INTO THIS 

2093
01:34:57,574 --> 01:34:58,975
FIELD.  SO, YOU KNOW, I THINK A 

2094
01:34:58,975 --> 01:35:02,445
LOT OF TIMES THE FDA SEES THAT A

2095
01:35:02,445 --> 01:35:03,546
COMPANY IS DOING IT WELL OR THAT

2096
01:35:03,546 --> 01:35:05,815
A PRODUCT IS DOING IT WELL, THEY

2097
01:35:05,815 --> 01:35:06,683
KNOW THERE'S A PROBLEM OUT THERE

2098
01:35:06,683 --> 01:35:07,784
AND YOU PLAY A LITTLE BIT OF 

2099
01:35:07,784 --> 01:35:09,452
THIS GUESS WHAT I'M THINKING 

2100
01:35:09,452 --> 01:35:11,154
GAME BECAUSE THEY KNOW WHAT THE 

2101
01:35:11,154 --> 01:35:12,255
ANSWER IS OR AT LEAST THEY KNOW 

2102
01:35:12,255 --> 01:35:13,990
WHAT THE PROBLEM IS BUT WHAT 

2103
01:35:13,990 --> 01:35:15,692
INFORMATION THEY CAN SHARE WITH 

2104
01:35:15,692 --> 01:35:16,359
YOU IS LIMITED AND SO YOU NEED 

2105
01:35:16,359 --> 01:35:17,994
TO BE AWARE OF THAT GETTING INTO

2106
01:35:17,994 --> 01:35:19,329
THIS AND I THINK ANOTHER WAY 

2107
01:35:19,329 --> 01:35:21,231
THAT THIS REALLY MANIFESTS 

2108
01:35:21,231 --> 01:35:22,465
ITSELF ESPECIALLY AS WE TRY AND 

2109
01:35:22,465 --> 01:35:25,201
TAKE DISCOVERY TO THE CLINIC, 

2110
01:35:25,201 --> 01:35:29,039
THROUGH AN ACADEMIC ROUTE IS 

2111
01:35:29,039 --> 01:35:31,207
THROUGH THE NOTION OF GLP AND 

2112
01:35:31,207 --> 01:35:32,742
SAVING YOUR DATA THE RIGHT WAY 

2113
01:35:32,742 --> 01:35:36,179
AND I THINK THE FDA'S BEEN 

2114
01:35:36,179 --> 01:35:37,580
WONDERFUL FROM THAT POST THAT 

2115
01:35:37,580 --> 01:35:40,116
THINGS DO NOT HAVE TO BE JLP BUT

2116
01:35:40,116 --> 01:35:42,385
YOU HAVE TO GIVE THEM DATA IN A 

2117
01:35:42,385 --> 01:35:45,855
WAY THAT THEY CAN REPLICATE YOUR

2118
01:35:45,855 --> 01:35:46,489
EXPERIMENT AND YOU CAN DEVELOP 

2119
01:35:46,489 --> 01:35:50,827
THAT CULTURE AND DO IT VERY 

2120
01:35:50,827 --> 01:35:51,327
EFFECTIVELY.

2121
01:35:51,327 --> 01:35:55,098
>> YEP.  THANK YOU.

2122
01:35:55,098 --> 01:35:58,435
>> THE INDIVIDUAL
EXPERIMENTS 

2123
01:35:58,435 --> 01:35:59,803
FOR INDUSTRY ARE GOING TO BE 

2124
01:35:59,803 --> 01:36:04,040
PROPRIETARY BUT WE DO NEED TO BE

2125
01:36:04,040 --> 01:36:05,408
COMPETITIVE.  WHAT THAT MEANS TO

2126
01:36:05,408 --> 01:36:08,912
ME IS THAT AS ACADEMICS WE 

2127
01:36:08,912 --> 01:36:10,246
PRODUCE DATA THAT THEN CAN BE 

2128
01:36:10,246 --> 01:36:13,883
USED TO ANSWER THESE QUESTIONS 

2129
01:36:13,883 --> 01:36:17,487
MORE GLOBALLY.  AND SO THAT'S MY

2130
01:36:17,487 --> 01:36:21,324
THINKING IS YES A LOT OF THIS IS

2131
01:36:21,324 --> 01:36:23,960
MOVING INTO MANUFACTURING 

2132
01:36:23,960 --> 01:36:25,795
COMPANIES THAT DO DO THAT.  

2133
01:36:25,795 --> 01:36:27,097
THERE ARE COMPANIES THAT ARE 

2134
01:36:27,097 --> 01:36:29,199
DEVELOPING PRODUCTS.  BUT IF WE 

2135
01:36:29,199 --> 01:36:31,401
AS A GROUP CAN PRODUCE THE DATA 

2136
01:36:31,401 --> 01:36:33,069
THAT CAN HELP ANSWER THE 

2137
01:36:33,069 --> 01:36:36,306
QUESTION THAT YOU JUST RAISED OF

2138
01:36:36,306 --> 01:36:38,074
WHAT IS GOOD ENOUGH AND THAT 

2139
01:36:38,074 --> 01:36:41,845
BECOMES ANSWERABLE WITH OUR 

2140
01:36:41,845 --> 01:36:43,046
PRECOMPETITIVE DATA WITHOUT 

2141
01:36:43,046 --> 01:36:44,681
HAVING TO GO TO THE COMPANY THAT

2142
01:36:44,681 --> 01:36:46,683
IS TO ME IS A VISION OF HOW WE 

2143
01:36:46,683 --> 01:36:52,288
CAN ACTUALLY MOVE THINGS FORWARD

2144
01:36:52,288 --> 01:36:52,422
.

2145
01:36:52,422 --> 01:36:56,926
>> THANKS.  ALAN, SORRY. 
ALAN 

2146
01:36:56,926 --> 01:36:58,261
FIRST AND THEN JEN.

2147
01:36:58,261 --> 01:37:01,264
>> SO FOLLOWING UP ON
THAT.  

2148
01:37:01,264 --> 01:37:05,301
DR. CAMP MENTIONED THE NEED FOR 

2149
01:37:05,301 --> 01:37:08,037
BETTER ANIMAL MODELS.  

2150
01:37:08,037 --> 01:37:10,406
ESPECIALLY LARGE ANIMAL MODELS. 

2151
01:37:10,406 --> 01:37:12,308
EVERY TIME WALK INTO AN OR WITH 

2152
01:37:12,308 --> 01:37:15,545
A BIG IT'S A 15,000 DOLLAR 

2153
01:37:15,545 --> 01:37:17,447
INVESTMENT AND I'M PUTTING HUMAN

2154
01:37:17,447 --> 01:37:20,416
CELLS IN A PIG AND THE PIGS DIE 

2155
01:37:20,416 --> 01:37:25,555
FROM THE IMMUNOSUPPRESSION.  WE 

2156
01:37:25,555 --> 01:37:27,457
WORK WITH THE EYE SO WE USE 

2157
01:37:27,457 --> 01:37:28,792
IMPLANTS AND SO ON BUT WE STILL 

2158
01:37:28,792 --> 01:37:33,429
GET REJECTION REGARDLESS.  AND 

2159
01:37:33,429 --> 01:37:37,400
SO IF WE WERE ABLE TO BRING DATA

2160
01:37:37,400 --> 01:37:41,538
TO THE AGENCY USING PIG MODELS 

2161
01:37:41,538 --> 01:37:44,374
AND I MEAN SAFETY MODELS IN 

2162
01:37:44,374 --> 01:37:45,975
PARTICULAR.  THAT ALLOW US TO 

2163
01:37:45,975 --> 01:37:47,677
CONSIDER THE IMPURITIES IN OUR 

2164
01:37:47,677 --> 01:37:49,445
SAMPLES SO DR. STERN, FOR 

2165
01:37:49,445 --> 01:37:51,214
EXAMPLE, SHOWED US MULTIPLE 

2166
01:37:51,214 --> 01:37:53,383
DIFFERENT CELL TYPES IN HIS 

2167
01:37:53,383 --> 01:37:55,485
PREPARATION.  THAT MAY ALL BE 

2168
01:37:55,485 --> 01:37:56,986
RPE AT DIFFERENT STAGES FOR 

2169
01:37:56,986 --> 01:37:58,755
EXAMPLE BUT SOME ARE GOING TO BE

2170
01:37:58,755 --> 01:38:00,256
MORE EFFICACIOUS THAN OTHERS THE

2171
01:38:00,256 --> 01:38:03,159
QUESTION IS DO THE IMPURITIES 

2172
01:38:03,159 --> 01:38:05,128
MATTER?  WE KNOW THAT THERE'S 

2173
01:38:05,128 --> 01:38:07,197
SOME THAT MATTER BECAUSE THERE'S

2174
01:38:07,197 --> 01:38:10,300
POTENTIAL FOR TERRA TO MA 

2175
01:38:10,300 --> 01:38:11,668
FORMATION FOR EXAMPLE AND THE 

2176
01:38:11,668 --> 01:38:13,203
QUESTION OF HAVING THE LOT 

2177
01:38:13,203 --> 01:38:15,572
RELEASE ASSAYS, FOR EXAMPLE, 

2178
01:38:15,572 --> 01:38:17,273
COULD BE POTENTIALLY NEGATED IF 

2179
01:38:17,273 --> 01:38:20,476
WE HAD PROPERLY ANIMAL MODELS TO

2180
01:38:20,476 --> 01:38:22,078
EVALUATE IF THERE'S A POSED RISK

2181
01:38:22,078 --> 01:38:24,047
TO SAFETY AND TO DO THIS AT 

2182
01:38:24,047 --> 01:38:26,182
EARLY STAGES AND NOT AT THE 

2183
01:38:26,182 --> 01:38:29,819
SAFETY STUDIES AND IN ANIMAL 

2184
01:38:29,819 --> 01:38:30,920
MODELS THAT DON'T REQUIRE THE 

2185
01:38:30,920 --> 01:38:32,455
LEVEL OF IMMUNOSUPPRESSION THAT 

2186
01:38:32,455 --> 01:38:35,458
WE WORK WITH.

2187
01:38:35,458 --> 01:38:38,828
>> THANK YOU.

2188
01:38:38,828 --> 01:38:41,731
>> SO COMING BACK TO THE
STEM 

2189
01:38:41,731 --> 01:38:43,700
CELLS AND THE FDA IN OUR CASE, 

2190
01:38:43,700 --> 01:38:45,435
WE WERE USING BONE MARROW 

2191
01:38:45,435 --> 01:38:48,438
ASPIRATE SO CLEARLY THERE WAS 

2192
01:38:48,438 --> 01:38:50,473
TALKING THERE THAT IS VERY 

2193
01:38:50,473 --> 01:38:51,641
IMPORTANT.  ONE THEY ARE NOT 

2194
01:38:51,641 --> 01:38:57,013
PURE STEM CELLS AND ALL THAT.  

2195
01:38:57,013 --> 01:38:59,749
BUT THE SECOND THING TOO IS THEY

2196
01:38:59,749 --> 01:39:03,086
ARE NOT EXPENDED AND THAT HAS 

2197
01:39:03,086 --> 01:39:05,288
PAVED THE WAY FOR US TO GET 

2198
01:39:05,288 --> 01:39:06,789
CLEARANCE WITH THE FDA AND 

2199
01:39:06,789 --> 01:39:09,893
AGAIN, I THINK, YOU KNOW, WE 

2200
01:39:09,893 --> 01:39:11,094
SHOULD THINK AS A GROUP THAT 

2201
01:39:11,094 --> 01:39:17,066
I'VE BEEN WORKING FOR A LONG 

2202
01:39:17,066 --> 01:39:18,935
TIME TO EXPEND A STEM CELL 

2203
01:39:18,935 --> 01:39:20,169
FOREVER BEFORE I INJECT THEM.  I

2204
01:39:20,169 --> 01:39:22,338
KNOW IN SOME CASE WE NEED 

2205
01:39:22,338 --> 01:39:24,540
EXTENSION.  I KNOW THOROUGHLY IN

2206
01:39:24,540 --> 01:39:26,109
SOME CASE WE NEED EXTENSION BUT 

2207
01:39:26,109 --> 01:39:27,944
IN SOME CASE YOU DON'T NEED 

2208
01:39:27,944 --> 01:39:30,346
EXTENSION AND IN OUR CASE THAT, 

2209
01:39:30,346 --> 01:39:31,214
YOU KNOW, THAT WAS WHAT HAPPENED

2210
01:39:31,214 --> 01:39:33,917
SO CLEARLY I THINK, BUT WE 

2211
01:39:33,917 --> 01:39:35,985
EMBODY THAT RIGHT AWAY.  I HAVE 

2212
01:39:35,985 --> 01:39:38,488
A TEAM OF PEOPLE THAT WORK WITH 

2213
01:39:38,488 --> 01:39:40,590
THE FDA AND I WANT TO MAKE SURE 

2214
01:39:40,590 --> 01:39:42,525
I EDUCATE THEM AND THEY HELP ME 

2215
01:39:42,525 --> 01:39:45,495
TO GO THROUGH THAT, YOU KNOW, 

2216
01:39:45,495 --> 01:39:46,429
PROCESS.  AND THE FINAL THING 

2217
01:39:46,429 --> 01:39:49,599
FOR US, THE BIGGEST PROBLEM WAS 

2218
01:39:49,599 --> 01:39:51,434
MORE THE DRUG WE WERE USING.  WE

2219
01:39:51,434 --> 01:39:58,374
ARE USING ENOUGH LABELED DRUG TO

2220
01:39:58,374 --> 01:40:01,778
REDUCE THIS AND THERE WE HAD TO 

2221
01:40:01,778 --> 01:40:05,815
HAVE THE FDA APPROVAL AND I 

2222
01:40:05,815 --> 01:40:08,384
COLLABORATE WITH THE CLINIC.  

2223
01:40:08,384 --> 01:40:10,119
AND IF YOU HAVE SOMEONE IN THE 

2224
01:40:10,119 --> 01:40:11,654
FIELD THAT IS DOING CLINICAL 

2225
01:40:11,654 --> 01:40:13,423
TRIALS ON THE SAME DRUG MAYBE 

2226
01:40:13,423 --> 01:40:16,693
YOU CAN PIGGYBACK ON WHAT THEY 

2227
01:40:16,693 --> 01:40:20,163
DO AND THAT REALLY IS PAVE WHAT 

2228
01:40:20,163 --> 01:40:23,700
YOU DO AS WELL.

2229
01:40:23,700 --> 01:40:27,270
>> THANK YOU.  TONY, GO
AHEAD.

2230
01:40:27,270 --> 01:40:30,239
>> I JUST WANTED TO -- I
WANTED 

2231
01:40:30,239 --> 01:40:31,374
TO BRING UP ONE MORE THEME THAT 

2232
01:40:31,374 --> 01:40:33,009
WAS -- WE SAW IN THE FIRST 

2233
01:40:33,009 --> 01:40:35,979
SESSION WHICH WAS THIS 

2234
01:40:35,979 --> 01:40:37,613
COMPARISON BETWEEN OFF THE SHELF

2235
01:40:37,613 --> 01:40:40,583
ALOE PRODUCTS AND WHICH ARE 

2236
01:40:40,583 --> 01:40:43,519
IMMUNO REACTIVE AND THEN 

2237
01:40:43,519 --> 01:40:48,291
AUTOLOGOUS LONGER MANUFACTURING 

2238
01:40:48,291 --> 01:40:52,028
ROUTES WITH VARIABILITY THAT ARE

2239
01:40:52,028 --> 01:40:55,565
RELATIVELY INERT AND THIS 

2240
01:40:55,565 --> 01:40:59,435
BALANCE OF HOW TO OVERCOME THIS 

2241
01:40:59,435 --> 01:41:02,238
TRANSPLANTATION BARRIER IS I 

2242
01:41:02,238 --> 01:41:05,408
THINK A BIG ISSUE BECAUSE IT'S 

2243
01:41:05,408 --> 01:41:06,943
LESS COST.  SO EVERYONE'S 

2244
01:41:06,943 --> 01:41:08,311
TALKING ABOUT IT BUT IT'S IN THE

2245
01:41:08,311 --> 01:41:12,382
ROOM WHERE YOU HAVE TO DEAL WITH

2246
01:41:12,382 --> 01:41:12,548
IT.

2247
01:41:12,548 --> 01:41:17,653
>> I THINK ALAN MENTIONED
THE 

2248
01:41:17,653 --> 01:41:19,856
UNIVERSAL DONORS AND I WAS 

2249
01:41:19,856 --> 01:41:21,924
THINKING, WOULD IT EVEN BE 

2250
01:41:21,924 --> 01:41:23,092
POSSIBLE?  WOULD IT BE IDEAL OFF

2251
01:41:23,092 --> 01:41:25,194
THE SHELF AND DO WE HAVE A 

2252
01:41:25,194 --> 01:41:26,829
DEFINITION FOR THAT?  AND SO 

2253
01:41:26,829 --> 01:41:30,366
MAYBE ALAN YOU WANT TO COMMENT 

2254
01:41:30,366 --> 01:41:34,704
ON THAT?

2255
01:41:34,704 --> 01:41:37,206
>> WELL I DON'T HAVE IT. 
I 

2256
01:41:37,206 --> 01:41:38,341
UNDERSTAND THAT THERE'S SOME 

2257
01:41:38,341 --> 01:41:39,809
PRODUCED KNOCKOUTS THAT ARE 

2258
01:41:39,809 --> 01:41:41,844
WORKING IN OTHERS' HANDS BUT THE

2259
01:41:41,844 --> 01:41:43,346
QUESTION BECOMES ONE OF 

2260
01:41:43,346 --> 01:41:45,548
MANUFACTURING, FROM A REGULATORY

2261
01:41:45,548 --> 01:41:46,315
PERSPECTIVE, AS I'VE MOVED 

2262
01:41:46,315 --> 01:41:47,817
THROUGH THIS PROCESS AND WE HAVE

2263
01:41:47,817 --> 01:41:51,120
NOT YET FILED AN IND BUT WE'VE 

2264
01:41:51,120 --> 01:41:52,688
HAD MULTIPLE MEETINGS WITH THE 

2265
01:41:52,688 --> 01:41:54,390
AGENCY THE PROBLEM IS YOU START 

2266
01:41:54,390 --> 01:41:56,859
WITH A DONOR CELL MAYBE WHAT'S 

2267
01:41:56,859 --> 01:41:59,095
COLLECTED UNDER GTPS AND THEN 

2268
01:41:59,095 --> 01:42:00,563
MOVE TO THE PRODUCTION OF A LINE

2269
01:42:00,563 --> 01:42:02,799
AND THEN THE PRODUCTION OF THE 

2270
01:42:02,799 --> 01:42:04,767
IPSC LINE TO A DIFFERENTIATION. 

2271
01:42:04,767 --> 01:42:06,602
IT IS A SUPER COMPLICATED 

2272
01:42:06,602 --> 01:42:07,837
PROCESS.  AND THEN THERE MAY 

2273
01:42:07,837 --> 01:42:09,338
BE'RE PARTS TO THAT.  MAYBE YOU 

2274
01:42:09,338 --> 01:42:10,940
HAVE, YOU KNOW, SURGICAL 

2275
01:42:10,940 --> 01:42:12,909
INSTRUMENTS THAT ARE PART OF THE

2276
01:42:12,909 --> 01:42:13,876
PACKAGING, A SCAFFOLD THAT'S A 

2277
01:42:13,876 --> 01:42:15,678
PART OF IT SO THIS IS A REALLY 

2278
01:42:15,678 --> 01:42:18,948
COMPLEX THING AND THEN TO ADD 

2279
01:42:18,948 --> 01:42:24,821
ONTO THAT THE REMOVAL, SAY, OF 

2280
01:42:24,821 --> 01:42:26,856
MHA GENES DO AND DOING THAT BY 

2281
01:42:26,856 --> 01:42:32,829
GENE EDITING KNEW  -- NOW YOU'RE

2282
01:42:32,829 --> 01:42:34,130
TAKING A CELL THAT WAS PRODUCED 

2283
01:42:34,130 --> 01:42:36,065
AND NOW YOU'RE GOING TO MESS 

2284
01:42:36,065 --> 01:42:37,200
WITH THAT GOOD CELL LINE AND 

2285
01:42:37,200 --> 01:42:40,436
MAYBE IT'S GOING TO TAKE ANOTHER

2286
01:42:40,436 --> 01:42:41,938
20 PASSAGES WHAT HAVE YOU DONE 

2287
01:42:41,938 --> 01:42:43,206
GENETICALLY AT THAT POINT?  HOW 

2288
01:42:43,206 --> 01:42:46,943
MANY PASSAGES HAVE YOU BEEN 

2289
01:42:46,943 --> 01:42:47,743
THROUGH?  WHAT ARE THE 

2290
01:42:47,743 --> 01:42:48,811
CONSEQUENCES OF THAT?  I THINK 

2291
01:42:48,811 --> 01:42:50,079
IT'S IMPORTANT TO GET THERE TO 

2292
01:42:50,079 --> 01:42:51,481
GET OFF THE SHELF PRODUCTS IN 

2293
01:42:51,481 --> 01:42:53,116
THE MARKETPLACE.  BUT I THINK 

2294
01:42:53,116 --> 01:42:58,488
THAT WE HAVE TO HAVE A MEANS OF 

2295
01:42:58,488 --> 01:42:59,088
INTRODUCING THAT UNIVERSAL 

2296
01:42:59,088 --> 01:43:01,190
DONORNESS FOR LACK OF A BETTER 

2297
01:43:01,190 --> 01:43:04,527
TERM AT THE TIME OF 

2298
01:43:04,527 --> 01:43:05,528
REPROGRAMMING SO IT DOESN'T 

2299
01:43:05,528 --> 01:43:06,863
CAUSE ADDITIONAL CHANGES AND 

2300
01:43:06,863 --> 01:43:10,466
ALLOWS US TO SELECT THE CELLS AT

2301
01:43:10,466 --> 01:43:17,840
THE EARLIEST STAGE POSSIBLE.  I 

2302
01:43:17,840 --> 01:43:19,375
DO KNOW A GROUP THAT IS WORKING 

2303
01:43:19,375 --> 01:43:29,919
ON THAT  BUT THEY HAVEN'T GOTTEN

2304
01:43:30,486 --> 01:43:31,888
TO THAT YET.

2305
01:43:31,888 --> 01:43:33,823
>> I TRIED TO FIND THE
ANSWER ON

2306
01:43:33,823 --> 01:43:35,925
GOOGLE BUT I CAN'T QUITE 

2307
01:43:35,925 --> 01:43:39,228
REMEMBER I THINK THE COMPANY IS 

2308
01:43:39,228 --> 01:43:41,164
CALLED SOMETHING BUT THERE'S A 

2309
01:43:41,164 --> 01:43:46,636
NUMBER OF PAPERS WHERE THEY MAKE

2310
01:43:46,636 --> 01:43:50,039
UNIVERSAL STEM CELLS AND THEY 

2311
01:43:50,039 --> 01:43:54,710
USED A PRIMATE MODEL AND MADE 

2312
01:43:54,710 --> 01:43:57,747
THESE UNIVERSAL STEM CELLS.  YOU

2313
01:43:57,747 --> 01:44:00,983
CAN NOW DO IT FAIRLY 

2314
01:44:00,983 --> 01:44:02,385
EFFICIENTLY.  YOU CAN KNOCK OUT 

2315
01:44:02,385 --> 01:44:05,254
AN HLA CLASS ONE OR TWO AND AT 

2316
01:44:05,254 --> 01:44:06,222
THE SAME TIME AS YOU ARE 

2317
01:44:06,222 --> 01:44:08,224
KNOCKING IT OUT YOU CAN KNOCK IN

2318
01:44:08,224 --> 01:44:12,962
SOMETHING USEFUL LIKE HLA OR 

2319
01:44:12,962 --> 01:44:14,330
CD47 SO THEY'RE ACCOMPLISHING A 

2320
01:44:14,330 --> 01:44:17,533
LOT OF THINGS WITH MAYBE A 

2321
01:44:17,533 --> 01:44:19,769
COUPLE OF KNOCK OUT KNOCK IN 

2322
01:44:19,769 --> 01:44:22,471
STEPS AND SO IN THAT SHORT 

2323
01:44:22,471 --> 01:44:24,473
PERIOD OF TIME, THEY'RE ABLE TO 

2324
01:44:24,473 --> 01:44:32,114
GENERATE A PRETTY NICE CELL.

2325
01:44:32,114 --> 01:44:42,592
>> (SPEAKER FAR FROM MIC).

2326
01:44:43,192 --> 01:44:44,927
>> IT'S NOT THAT THE 

2327
01:44:44,927 --> 01:44:49,398
TECHNOLOGIES DON'T EXIST.  THERE

2328
01:44:49,398 --> 01:44:53,603
HAVE BEEN A DIFFERENT GROUPS.  

2329
01:44:53,603 --> 01:44:54,804
THE PROBLEM IS THE 

2330
01:44:54,804 --> 01:44:56,839
MANUFACTURING.  AND EACH STEP 

2331
01:44:56,839 --> 01:44:58,808
IMPOSES RISK AND WHEN YOU'RE 

2332
01:44:58,808 --> 01:45:01,277
TAKING AND AGAIN IN THE ALOE YES

2333
01:45:01,277 --> 01:45:04,614
NAYIC WORLD IS DIFFERENT FROM 

2334
01:45:04,614 --> 01:45:08,618
THE AWETOLOGIST WORLD.  I CAN 

2335
01:45:08,618 --> 01:45:10,319
USE THIS IN ONE PATIENT.  WHO 

2336
01:45:10,319 --> 01:45:13,155
CARES FROM AN ALOE YES NAYIC 

2337
01:45:13,155 --> 01:45:15,191
STANDPOINT I NEED A VERY 

2338
01:45:15,191 --> 01:45:16,792
EFFICIENT PRICE IN ORDER TO KEEP

2339
01:45:16,792 --> 01:45:17,793
THE PRICE DOWN AND MAKE THIS 

2340
01:45:17,793 --> 01:45:20,263
SOMETHING THAT IS UNIVERSAL FOR 

2341
01:45:20,263 --> 01:45:20,997
EVERYBODY. 

2342
01:45:20,997 --> 01:45:21,897
EVERYTHING I ADD TO THAT PROCESS

2343
01:45:21,897 --> 01:45:23,933
INCREASES THE COST OF GENERATING

2344
01:45:23,933 --> 01:45:26,335
THE CELL LINE AND INCREASES THE 

2345
01:45:26,335 --> 01:45:29,472
RISK AND ADDS TO THE REGULATORY 

2346
01:45:29,472 --> 01:45:31,907
BURDEN.  AND THAT'S WHERE A LOT 

2347
01:45:31,907 --> 01:45:33,776
OF THESE PROBLEMS REALLY 

2348
01:45:33,776 --> 01:45:35,878
ORIGINATE FROM IT'S NOT THAT THE

2349
01:45:35,878 --> 01:45:36,846
TECHNOLOGY ISN'T THERE.  IT'S 

2350
01:45:36,846 --> 01:45:38,481
THE REGULATORY BURDEN COMBINED 

2351
01:45:38,481 --> 01:45:47,223
WITH THE RISK TO PRODUCT.

2352
01:45:47,223 --> 01:45:48,124
>> THANK YOU.  DAN.

2353
01:45:48,124 --> 01:45:49,859
>> SO TO FOLLOW UP ON THE 

2354
01:45:49,859 --> 01:45:51,093
CONVERSATION I JUST WANT TO GO 

2355
01:45:51,093 --> 01:45:51,827
BACK TO SOMETHING THAT CHRIS 

2356
01:45:51,827 --> 01:45:54,463
SAID AND THE QUESTION IS, WHERE 

2357
01:45:54,463 --> 01:45:56,499
SHOULD MANUFACTURING BE?  AND 

2358
01:45:56,499 --> 01:45:58,868
WHAT'S THE BEST MEANS TO AN END 

2359
01:45:58,868 --> 01:46:01,237
POINT, RIGHT?  IS IT REALLY 

2360
01:46:01,237 --> 01:46:02,738
ACADEMIA?  OR IS THIS WHERE 

2361
01:46:02,738 --> 01:46:03,973
INDUSTRY PARTNERSHIP IS REALLY 

2362
01:46:03,973 --> 01:46:05,741
GOING TO BE CRITICAL, 

2363
01:46:05,741 --> 01:46:07,743
PARTICULARLY FOR IF YOU THINK 

2364
01:46:07,743 --> 01:46:11,113
THE VOLUME OF PRODUCT THAT YOU 

2365
01:46:11,113 --> 01:46:13,082
WANT TO EVENTUALLY PRODUCE IT 

2366
01:46:13,082 --> 01:46:15,384
INCORPORATES ALL THE SAFETY AND 

2367
01:46:15,384 --> 01:46:18,254
QUALITY CONTROL AND POTENCY AND 

2368
01:46:18,254 --> 01:46:20,089
THINGS LIKE THAT BUT ON THE 

2369
01:46:20,089 --> 01:46:22,958
OTHER HAND WE'RE ALL ADMISSIONS,

2370
01:46:22,958 --> 01:46:24,060
RIGHT?  AND THERE HAVE BEEN 

2371
01:46:24,060 --> 01:46:25,261
EXAMPLES IN THE PAST AND I WILL 

2372
01:46:25,261 --> 01:46:29,999
POINT TO MARTHA HERE BECAUSE NH 

2373
01:46:29,999 --> 01:46:32,435
HAD A PROGRAM CALLED THE PACT 

2374
01:46:32,435 --> 01:46:37,406
PROGRAM THAT SUNSETTED, RIGHT? 

2375
01:46:37,406 --> 01:46:39,909
BUT THE WHOLE GOAL WAS TO 

2376
01:46:39,909 --> 01:46:41,043
PROVIDE MATERIALS FOR CLINICAL 

2377
01:46:41,043 --> 01:46:42,078
INVESTIGATIONS SO WE'VE DONE 

2378
01:46:42,078 --> 01:46:44,880
THAT BEFORE.  IS THAT SOMETHING 

2379
01:46:44,880 --> 01:46:46,449
WE CAN DO AGAIN?  BUT BEEF IT UP

2380
01:46:46,449 --> 01:46:48,617
WITH THE TYPE OF FUNDING THAT 

2381
01:46:48,617 --> 01:46:52,288
WOULD ALLOW, AGAIN, THE 

2382
01:46:52,288 --> 01:46:53,923
RELIABILITY, REPRODUCIBILITY AND

2383
01:46:53,923 --> 01:46:56,559
MECHANISM, THINGS OF THAT 

2384
01:46:56,559 --> 01:46:56,826
NATURE.

2385
01:46:56,826 --> 01:46:58,094
>> YEAH, THANK YOU.  JENNA
OVER 

2386
01:46:58,094 --> 01:47:00,262
HERE AND THEN I WILL MOVE ONTO 

2387
01:47:00,262 --> 01:47:10,806
ANOTHER COMMON THEME I'VE HEARD.

2388
01:47:14,243 --> 01:47:17,680
>> WE KNOW THAT ADULT STEM
CELLS

2389
01:47:17,680 --> 01:47:21,917
OR TISSUE CELLS, THEY DON'T 

2390
01:47:21,917 --> 01:47:23,018
EXPRESS EQUALLY.  THEY EXPRESS 

2391
01:47:23,018 --> 01:47:25,221
IN CLASS ONE AND THEY EXPRESS G 

2392
01:47:25,221 --> 01:47:28,991
OR HLE.  SO THEREFORE THEY DON'T

2393
01:47:28,991 --> 01:47:31,527
STIMULATE T-CELL RESPONSES.  CAN

2394
01:47:31,527 --> 01:47:34,563
THEY STILL BE REJECTED? 

2395
01:47:34,563 --> 01:47:36,532
PROBABLY.  BUT IF WE START WITH 

2396
01:47:36,532 --> 01:47:40,736
A PLATFORM THAT IS ALREADY SET 

2397
01:47:40,736 --> 01:47:43,272
TO -- PRESENT THE CELLS, THEY 

2398
01:47:43,272 --> 01:47:46,876
PREVENT THE FETUS FOR BEING 

2399
01:47:46,876 --> 01:47:50,513
REJECTED TO THE MOTHER.  FROM 

2400
01:47:50,513 --> 01:47:52,448
PREVENTING BEING REJECTED.  SO 

2401
01:47:52,448 --> 01:47:55,217
IF YOU START WITH THOSE TYPE OF 

2402
01:47:55,217 --> 01:47:57,720
PLATFORMS WE ALREADY HAVE CELLS 

2403
01:47:57,720 --> 01:47:58,988
THAT CAN DO WHAT WE WANT TO DO 

2404
01:47:58,988 --> 01:48:03,859
THEN IT'S JUST USING THEM TO 

2405
01:48:03,859 --> 01:48:05,728
DELIVER SPECIFIC GENES OR 

2406
01:48:05,728 --> 01:48:07,196
DIFFERENTIATE THEM INTO SPECIFIC

2407
01:48:07,196 --> 01:48:07,897
POTENTIAL.  I THINK THE 

2408
01:48:07,897 --> 01:48:10,433
POTENTIAL IS OUT THERE WE JUST 

2409
01:48:10,433 --> 01:48:12,168
LIKE TO LOOK FOR THE CELLS THAT 

2410
01:48:12,168 --> 01:48:15,037
ARE RIGHT FOR WHAT WE WANT TO DO

2411
01:48:15,037 --> 01:48:16,906
AND THAT THEY ARE NOT 

2412
01:48:16,906 --> 01:48:19,809
IMMUNOGENIC IN NATURE TO START 

2413
01:48:19,809 --> 01:48:20,709
WITH.

2414
01:48:20,709 --> 01:48:22,778
>> YEP.  THANK YOU.  SO
ANOTHER 

2415
01:48:22,778 --> 01:48:23,879
COMMON THING I'VE HEARD IS 

2416
01:48:23,879 --> 01:48:29,185
ANIMAL MODELS, RIGHT?  WE HAVE 

2417
01:48:29,185 --> 01:48:30,886
INVESTIGATOR PRESENTED SUCH AS 

2418
01:48:30,886 --> 01:48:33,656
DENNIS IN HUMANS AND WE HAVE 

2419
01:48:33,656 --> 01:48:36,592
PEOPLE WORKING WITH PIGS AND 

2420
01:48:36,592 --> 01:48:39,028
OTHERS THINKING TRANSLATING FROM

2421
01:48:39,028 --> 01:48:42,364
MOUSE MODEL TO LARGE ANIMAL 

2422
01:48:42,364 --> 01:48:44,166
MODELS AND SO MY QUESTION IS ARE

2423
01:48:44,166 --> 01:48:49,238
THERE OTHER MODELS, I MEAN, WE 

2424
01:48:49,238 --> 01:48:50,973
ACTUALLY HEARD SOMEONE MENTIONED

2425
01:48:50,973 --> 01:48:53,108
DIGITAL.  AND IF YOU ARE AWARE 

2426
01:48:53,108 --> 01:48:55,911
NIH ACTUALLY RIGHT NOW IS 

2427
01:48:55,911 --> 01:48:57,480
DISCUSSING A COMMON FUND 

2428
01:48:57,480 --> 01:48:58,380
INITIATIVE COMPLEMENTARY 

2429
01:48:58,380 --> 01:49:03,419
ALTERNATIVE MODELS THAT YOU KNOW

2430
01:49:03,419 --> 01:49:05,254
FDA HAS CHANGED THEIR DRUG 

2431
01:49:05,254 --> 01:49:06,622
APPROVAL GUIDELINE AND THEN 

2432
01:49:06,622 --> 01:49:11,260
CHANGING ANIMAL MODELS TO MODELS

2433
01:49:11,260 --> 01:49:15,231
POSSIBLY IN VITRO MODELS I 

2434
01:49:15,231 --> 01:49:25,774
WONDER WHETHER, YOU KNOW, IF YOU

2435
01:49:43,325 --> 01:49:45,494
HAVE COMMENTS? ANY?

2436
01:49:45,494 --> 01:49:47,963
>> I THINK ANY MODEL IS 

2437
01:49:47,963 --> 01:49:50,432
IMPERFECT BUT IT DEPENDS ON THE 

2438
01:49:50,432 --> 01:49:52,101
QUESTION YOU'RE ASKING AND I 

2439
01:49:52,101 --> 01:49:54,470
TOOK STUFF FROM MICE TO HUMANS 

2440
01:49:54,470 --> 01:49:55,771
BECAUSE I WAS USING A DRUG THAT 

2441
01:49:55,771 --> 01:49:56,906
ALREADY HAD A KNOWN SAFETY 

2442
01:49:56,906 --> 01:49:59,275
PROFILE SO WE SHOWED ITS 

2443
01:49:59,275 --> 01:50:00,609
BIOLOGIC EFFECT WITH RELATION TO

2444
01:50:00,609 --> 01:50:02,411
THE MECHANISM OF ACTION OR 

2445
01:50:02,411 --> 01:50:03,812
PRODUCT THEY ALREADY KNEW IT WAS

2446
01:50:03,812 --> 01:50:08,384
SAFE AND SO WE COULD TAKE THAT 

2447
01:50:08,384 --> 01:50:09,618
LEAP OF FAITH IN OTHER 

2448
01:50:09,618 --> 01:50:11,720
SITUATIONS WE USED LARGE ANIMAL 

2449
01:50:11,720 --> 01:50:13,856
MODEL ONE OF THE THINGS THAT 

2450
01:50:13,856 --> 01:50:19,228
STARTED PAY BENEFITS RECENTLY IS

2451
01:50:19,228 --> 01:50:20,029
DOING LARGE TERM LARGE ANIMAL 

2452
01:50:20,029 --> 01:50:21,897
MODEL.  SO MUCH OF THIS IS JUST 

2453
01:50:21,897 --> 01:50:24,099
A TINY FRACTION OF THE ANIMAL'S 

2454
01:50:24,099 --> 01:50:27,236
LIFE SPAN.  WE HAD THE GOOD 

2455
01:50:27,236 --> 01:50:31,073
FORTUNE OF FOLLOWING A COHORT OF

2456
01:50:31,073 --> 01:50:32,841
ANIMALS AND THE DATA IS SO 

2457
01:50:32,841 --> 01:50:34,443
USEFUL IN HELPING YOU BRING YOUR

2458
01:50:34,443 --> 01:50:35,644
PRODUCT TO THE CLINIC AND 

2459
01:50:35,644 --> 01:50:38,547
FINALLY WITH THE RELATIONSHIP TO

2460
01:50:38,547 --> 01:50:40,950
THE CLINICAL TWIN.  ONE OF THE 

2461
01:50:40,950 --> 01:50:45,988
THINGS THAT'S PAID GREAT 

2462
01:50:45,988 --> 01:50:48,824
DIVIDENDS FOR US IS WHEN YOU 

2463
01:50:48,824 --> 01:50:50,059
SYNTHESIZE THESE MODELS AND PUT 

2464
01:50:50,059 --> 01:50:52,027
THEM TOGETHER AND IT'S PROVED 

2465
01:50:52,027 --> 01:50:54,363
USEFUL AND IN THE DEVELOPMENT 

2466
01:50:54,363 --> 01:50:54,597
PROCESS.

2467
01:50:54,597 --> 01:51:02,705
>> YEAH.  THANK YOU. 
JOHNNY?

2468
01:51:02,705 --> 01:51:04,273
>> IN OUR CASE WE DIDN'T
USE 

2469
01:51:04,273 --> 01:51:06,408
LARGE ANIMAL MODEL WE WENT FROM 

2470
01:51:06,408 --> 01:51:08,010
THE MOUSE THEORETICALLY TO THE 

2471
01:51:08,010 --> 01:51:09,378
PATIENT AS THE PREVIOUS SPEAKER.

2472
01:51:09,378 --> 01:51:15,117
I MEAN, A LOT OF WHAT WAS USED 

2473
01:51:15,117 --> 01:51:18,487
WAS ALREADY APPROVED.  BUT ALSO 

2474
01:51:18,487 --> 01:51:21,323
I WOULD LIKE TO STRESS IN THE 

2475
01:51:21,323 --> 01:51:27,997
LARGE AN MOLL  -- ANIMAL MODEL 

2476
01:51:27,997 --> 01:51:30,699
IT'S VERY EXPENSIVE.  WHEN YOU 

2477
01:51:30,699 --> 01:51:32,968
DO SHEEP ANIMAL STUDIES, IT'S 

2478
01:51:32,968 --> 01:51:34,703
VERY EXPENSIVE AND YOU CANNOT 

2479
01:51:34,703 --> 01:51:37,006
USE AS MUCH AS YOU WANT LIKE YOU

2480
01:51:37,006 --> 01:51:40,042
DO IN MICE.  YOU CANNOT EXTEND. 

2481
01:51:40,042 --> 01:51:43,646
WITH A HORSE.  I STRESS THAT 

2482
01:51:43,646 --> 01:51:45,414
SOMETIMES LARGE ANIMAL MODEL 

2483
01:51:45,414 --> 01:51:47,783
YES, THEY MIMIC MORE THE PATIENT

2484
01:51:47,783 --> 01:51:49,151
BUT THERE ARE MORE DIFFICULT TO 

2485
01:51:49,151 --> 01:51:52,855
FUND AND SOMETIME, YOU KNOW, THE

2486
01:51:52,855 --> 01:51:55,224
NUMBER OF ANIMAL MODEL YOU NEED 

2487
01:51:55,224 --> 01:51:56,825
YOU CANNOT DO IN LARGE ANIMAL 

2488
01:51:56,825 --> 01:51:57,026
MODEL.

2489
01:51:57,026 --> 01:52:05,300
>> YEAH.  GO AHEAD.

2490
01:52:05,300 --> 01:52:08,103
>> I THINK THE IDEA OF A
DIGITAL

2491
01:52:08,103 --> 01:52:10,906
TWIN IS INTERESTING BUT IS 

2492
01:52:10,906 --> 01:52:12,741
COMPLEMENTARY.  NOT OF 

2493
01:52:12,741 --> 01:52:14,009
CIRCUMVENTING LARGE AN MOLL 

2494
01:52:14,009 --> 01:52:15,678
MODELS IN THE FUTURE. 

2495
01:52:15,678 --> 01:52:16,979
IF YOU HAVE THERAPIES OUT THERE 

2496
01:52:16,979 --> 01:52:19,248
THAT ARE ACQUIRING THE DELIVERY 

2497
01:52:19,248 --> 01:52:21,250
SYSTEMS YOU NOT ONLY HAVE TO 

2498
01:52:21,250 --> 01:52:23,419
APPROVE THAT THOSE SYSTEMS, 

2499
01:52:23,419 --> 01:52:24,086
ROBOTIC ARMS OR WHATEVER IT IS 

2500
01:52:24,086 --> 01:52:25,788
IS SAFE IN THAT ENVIRONMENT.  

2501
01:52:25,788 --> 01:52:28,190
AND THEN YOU HAVE TO HAVE A 

2502
01:52:28,190 --> 01:52:29,992
TRAINING PATHWAY TO BE ABLE TO 

2503
01:52:29,992 --> 01:52:31,460
DISSEMINATE THAT KNOWLEDGE 

2504
01:52:31,460 --> 01:52:33,295
ACROSS THE CENTERS THAT -- ONE 

2505
01:52:33,295 --> 01:52:35,564
NEEDS TO ENROLL PATIENTS FOR.

2506
01:52:35,564 --> 01:52:41,236
>> THANK YOU.  TONY?

2507
01:52:41,236 --> 01:52:43,872
>> AS FAR AS LARGE ANIMAL
MODELS

2508
01:52:43,872 --> 01:52:46,041
I WANT TO MAKE SURE WE 

2509
01:52:46,041 --> 01:52:48,210
UNDERSTAND THE DIFFERENCE 

2510
01:52:48,210 --> 01:52:49,978
BETWEEN SMALL ANIMALS REQUIRED 

2511
01:52:49,978 --> 01:52:52,848
FOR THOSE DRUG SUBSTANCES AND 

2512
01:52:52,848 --> 01:52:53,849
LIVING CELL THERAPIES THAT 

2513
01:52:53,849 --> 01:52:56,485
REQUIRE IMMUNOLOGIC TOLERANCE.  

2514
01:52:56,485 --> 01:52:58,721
SO I THINK IF YOU MAKE A LARGE 

2515
01:52:58,721 --> 01:53:01,990
ANIMAL MODEL IT HAS TO BE IMMUNO

2516
01:53:01,990 --> 01:53:04,560
COMPETENT.  YOU HAVE TO IMMUNO 

2517
01:53:04,560 --> 01:53:07,996
SUPPRESS AND FOR WOUND HEALING 

2518
01:53:07,996 --> 01:53:08,664
IMMUNOSUPPRESSION AFFECTS WOUND 

2519
01:53:08,664 --> 01:53:10,933
HEALING INDIRECTLY SO I JUST 

2520
01:53:10,933 --> 01:53:12,634
WANT TO BE CLEAR THAT THIS CELL 

2521
01:53:12,634 --> 01:53:14,603
THERAPY TYPE IS DIFFERENT THAN A

2522
01:53:14,603 --> 01:53:18,807
SMALL MOLECULE AND WE MAY NOT 

2523
01:53:18,807 --> 01:53:19,775
NEED TO DO THE DISTRIBUTION THAT

2524
01:53:19,775 --> 01:53:21,877
ARE RELEVANT TO HUMANS BECAUSE 

2525
01:53:21,877 --> 01:53:22,845
WE'RE LOOKING AT TISSUE 

2526
01:53:22,845 --> 01:53:26,248
INTERACTIONS WHICH ARE MORE 

2527
01:53:26,248 --> 01:53:26,515
IMPORTANT.

2528
01:53:26,515 --> 01:53:28,183
>> THANK YOU.  I THINK
THEN 

2529
01:53:28,183 --> 01:53:30,853
BEHIND YOU AND THEN ROSEMARY 

2530
01:53:30,853 --> 01:53:31,286
OVER HERE.

2531
01:53:31,286 --> 01:53:34,823
>> SO, THIS DISCUSSION HAS
BEEN 

2532
01:53:34,823 --> 01:53:37,092
GOING ON FOR 40 YEARS, RIGHT?  

2533
01:53:37,092 --> 01:53:39,261
I'M NOT SURE WE'RE GOING TO GET 

2534
01:53:39,261 --> 01:53:40,395
ANYTHING USEFUL OUT OF THE 

2535
01:53:40,395 --> 01:53:42,698
ARGUMENT.  I THINK IT'S ALL 

2536
01:53:42,698 --> 01:53:44,032
CONTEXT SPECIFIC BUT THE WAY I 

2537
01:53:44,032 --> 01:53:47,369
THINK ABOUT IT IS DIFFERENTLY, 

2538
01:53:47,369 --> 01:53:48,537
RIGHT?  AND IT REALLY ENDS UP 

2539
01:53:48,537 --> 01:53:51,306
THAT THE CLINICAL INVESTIGATIONS

2540
01:53:51,306 --> 01:53:53,175
THAT ARE GOING TO GET THE MOST 

2541
01:53:53,175 --> 01:53:54,643
INFORMATION I THINK ONE WAY OF 

2542
01:53:54,643 --> 01:53:56,879
DOING IT IS -- AND IDENTIFY 

2543
01:53:56,879 --> 01:53:58,013
ADVOCATED FAR LONG TIME IS WHEN 

2544
01:53:58,013 --> 01:54:00,149
YOU DO THAT INITIAL PHASE ONE 

2545
01:54:00,149 --> 01:54:03,485
AND MOVE ONTO PHASE TWO YOU 

2546
01:54:03,485 --> 01:54:04,953
ABSOLUTELY BUILD IN AS MANY 

2547
01:54:04,953 --> 01:54:08,390
MECKISTIC END POINTS AS YOU CAN.

2548
01:54:08,390 --> 01:54:09,858
NOT JUST CLINICAL BUT YOU TAKE 

2549
01:54:09,858 --> 01:54:14,630
BLOOD, SAMPLES, YOU MEASURE 

2550
01:54:14,630 --> 01:54:15,497
INFLAMMATORY THINGS AND YOU BASE

2551
01:54:15,497 --> 01:54:17,833
THAT ON THE HYPOTHESIS OF ACTION

2552
01:54:17,833 --> 01:54:20,569
AND YOU TRY TO INVESTIGATE THAT 

2553
01:54:20,569 --> 01:54:23,172
AND THIS IS WHERE WE AS A GROUP 

2554
01:54:23,172 --> 01:54:24,606
COULD PROVIDE FUNDING FOR THAT 

2555
01:54:24,606 --> 01:54:26,708
TYPE OF THING.  IT'S EXPENSIVE 

2556
01:54:26,708 --> 01:54:28,911
ENOUGH TO DO A CLINICAL 

2557
01:54:28,911 --> 01:54:29,678
INVESTIGATION WITH ALL THE 

2558
01:54:29,678 --> 01:54:32,581
CLINICAL END POINTS AND 

2559
01:54:32,581 --> 01:54:34,483
EVERYTHING ABOUT EXTRA FUNDING 

2560
01:54:34,483 --> 01:54:37,419
OR MECHANISTIC INVESTIGATIONS I 

2561
01:54:37,419 --> 01:54:39,988
THINK IT WOULD BE REALLY 

2562
01:54:39,988 --> 01:54:40,222
HELPFUL.

2563
01:54:40,222 --> 01:54:42,391
>> THANK YOU.  I THINK WAS
THERE

2564
01:54:42,391 --> 01:54:45,194
ONE OVER HERE?  YEAH.  YEAH.  

2565
01:54:45,194 --> 01:54:51,867
THEN WHEN ROSEMA ROSEMARY. 

2566
01:54:51,867 --> 01:54:53,435
THEN WHEN ROSEMA ROSEMARY.

2567
01:54:53,435 --> 01:54:56,271
>> I ALSO WANT TO DISCUSS 

2568
01:54:56,271 --> 01:54:58,874
PREDICTIVE BIOMARKER.  THERE'S A

2569
01:54:58,874 --> 01:55:01,076
CHALLENGE, YOU CANNOT HAVE A 

2570
01:55:01,076 --> 01:55:05,147
GOOD -- YOU KNOW, INFORMATION 

2571
01:55:05,147 --> 01:55:07,883
DOING THESE STUDIES ON ANIMALS. 

2572
01:55:07,883 --> 01:55:09,751
SOMETIME MAYBE BUT MOSTLY IN MY 

2573
01:55:09,751 --> 01:55:11,019
EXPERIENCE, YOU KNOW, THEY 

2574
01:55:11,019 --> 01:55:13,255
BEHAVE, THINGS BEHAVE VERY 

2575
01:55:13,255 --> 01:55:15,724
DIFFERENT WHEN THERAPY IS 

2576
01:55:15,724 --> 01:55:18,493
APPLIED THAN ON A HUMAN.  AND 

2577
01:55:18,493 --> 01:55:21,496
ALSO -- SO THESE BIOMARKER 

2578
01:55:21,496 --> 01:55:24,600
STUDIES SHOULD BE DONE ON 

2579
01:55:24,600 --> 01:55:27,502
HEALTHY VOLUNTEERS OR DISEASE 

2580
01:55:27,502 --> 01:55:29,004
PATIENTS.  SO, AND, 

2581
01:55:29,004 --> 01:55:31,240
ACCESSIBILITY, HOW TO ACCESS 

2582
01:55:31,240 --> 01:55:33,575
THESE SAMPLES IT'S LIKE A MAJOR 

2583
01:55:33,575 --> 01:55:35,644
CHALLENGE.  I SEE, LIKE, 

2584
01:55:35,644 --> 01:55:36,345
DEPARTMENT OF DEFENSE AND SOME 

2585
01:55:36,345 --> 01:55:39,248
OF THE OTHER FUNDING AGENCIES 

2586
01:55:39,248 --> 01:55:42,317
ARE OPENING UP SOME RFAS IN THAT

2587
01:55:42,317 --> 01:55:44,653
RESPECT BUT WHEN YOU GO AND 

2588
01:55:44,653 --> 01:55:45,787
APPLY BECAUSE THERE IS NOT MUCH 

2589
01:55:45,787 --> 01:55:47,155
PRELIMINARY DATA YOU CAN 

2590
01:55:47,155 --> 01:55:49,224
GENERATE SO YOU KNOW WHAT THE 

2591
01:55:49,224 --> 01:55:52,327
RESPONSE IS SO JUST SOMETHING TO

2592
01:55:52,327 --> 01:55:53,729
THINK ABOUT MAYBE WE CAN ALSO 

2593
01:55:53,729 --> 01:55:56,265
HAVE ONE OF THIS AREA IN THE 

2594
01:55:56,265 --> 01:55:59,067
FUNDING.  AND I WANT TO COMMENT 

2595
01:55:59,067 --> 01:56:01,236
ON PACT ACTUALLY.  WE -- OUR 

2596
01:56:01,236 --> 01:56:04,273
FACILITY WAS PART OF PACT FOR 

2597
01:56:04,273 --> 01:56:06,241
FIVE YEARS.  I CLOSELY WORKED 

2598
01:56:06,241 --> 01:56:08,810
WITH MARTHA.  I FELT THAT THIS 

2599
01:56:08,810 --> 01:56:10,312
WAS REALLY A VERY GOOD 

2600
01:56:10,312 --> 01:56:13,849
INITIATIVE TAKEN BY NIH AND WHAT

2601
01:56:13,849 --> 01:56:16,618
WE HAVE DONE DURING THAT TIME, 

2602
01:56:16,618 --> 01:56:18,754
YOU KNOW, IT'S -- A BIG 

2603
01:56:18,754 --> 01:56:20,923
DIFFERENCE BETWEEN GMP FACILITY 

2604
01:56:20,923 --> 01:56:25,193
AND ACADEMIA VERSUS A COMPANY.  

2605
01:56:25,193 --> 01:56:26,261
BUT THESE FIVE -- I MEAN, WE 

2606
01:56:26,261 --> 01:56:28,864
WERE PART OF THE LAST RENEWAL 

2607
01:56:28,864 --> 01:56:31,233
BUT THESE FIVE-SIX YEARS OUR 

2608
01:56:31,233 --> 01:56:32,901
FACILITY, WE WERE ABLE TO DO SO 

2609
01:56:32,901 --> 01:56:35,170
MUCH MORE BECAUSE OF THIS 

2610
01:56:35,170 --> 01:56:37,239
PLATFORM AVAILABLE AND THEY WERE

2611
01:56:37,239 --> 01:56:38,640
LIKE OUR OWN FUNDING GRANTS AND 

2612
01:56:38,640 --> 01:56:41,143
A LOT OF OTHER INVESTIGATORS.  

2613
01:56:41,143 --> 01:56:44,279
THAT'S SOMETHING ALSO TO THINK 

2614
01:56:44,279 --> 01:56:45,747
ABOUT IT, MAYBE BRINGING 

2615
01:56:45,747 --> 01:56:47,249
SOMETHING BACK LIKE THAT IT WILL

2616
01:56:47,249 --> 01:56:51,053
BE GREAT BECAUSE AS I SAID IN MY

2617
01:56:51,053 --> 01:56:53,455
TALK TOO THAT DEVELOPING IN AN 

2618
01:56:53,455 --> 01:56:55,023
ONGOING MAINTENANCE AND ON 

2619
01:56:55,023 --> 01:56:56,058
ONGOING DEVELOPMENT AND MAKING 

2620
01:56:56,058 --> 01:56:59,594
SURE SCALING UP CHARACTERIZATION

2621
01:56:59,594 --> 01:57:02,097
LEARNING ABOUT YOUR PRODUCT IS 

2622
01:57:02,097 --> 01:57:03,932
EXTREMELY IMPORTANT.  THANK YOU.

2623
01:57:03,932 --> 01:57:05,600
>> THANK YOU.  BIOMARKERS 

2624
01:57:05,600 --> 01:57:09,438
CERTAINLY EXTREMELY, EXTREMELY 

2625
01:57:09,438 --> 01:57:18,413
IMPORTANT.  ROSEMARY.

2626
01:57:18,413 --> 01:57:23,919
>> SO ROSEMARY, ARMY,
VIS-A-VIS 

2627
01:57:23,919 --> 01:57:26,455
ON MODELS I LOVE THE IDEA.  THE 

2628
01:57:26,455 --> 01:57:28,190
CONCEPT.  THAT NO MODEL IS 

2629
01:57:28,190 --> 01:57:32,194
PERFECT.  OF COURSE.  BUT WE CAN

2630
01:57:32,194 --> 01:57:33,829
MAYBE THINK ABOUT COMBINING 

2631
01:57:33,829 --> 01:57:35,497
MODELS TO GET US CLOSER TO 

2632
01:57:35,497 --> 01:57:37,366
ANSWER BY TAKING THE DATA THAT 

2633
01:57:37,366 --> 01:57:39,134
COMES OUT OF THOSE AND COMBINING

2634
01:57:39,134 --> 01:57:41,269
THEM WITH AI FACILITATED TOOLS 

2635
01:57:41,269 --> 01:57:43,839
TO GET CLOSER TO ANSWERS THAT 

2636
01:57:43,839 --> 01:57:46,475
MIGHT GET US TO THE CLINIC 

2637
01:57:46,475 --> 01:57:48,377
FASTER AND SPECIFICALLY ON 

2638
01:57:48,377 --> 01:57:50,012
THINKING THAT THE ADVANCEMENTS 

2639
01:57:50,012 --> 01:57:52,280
IN TISSUE CHIPS OVER THE LAST 

2640
01:57:52,280 --> 01:57:54,116
TEN YEARS HAVE BEEN PRETTY 

2641
01:57:54,116 --> 01:57:56,952
DRAMATIC AND ONE OF THE THINGS 

2642
01:57:56,952 --> 01:57:59,087
THAT I ALWAYS THOUGHT WAS A 

2643
01:57:59,087 --> 01:58:00,655
TREMENDOUS POTENTIAL ADVANTAGE 

2644
01:58:00,655 --> 01:58:04,760
ABOUT USING TISSUE CHIPS WAS TO 

2645
01:58:04,760 --> 01:58:06,261
DO PATIENT MODELING AND SO, FOR 

2646
01:58:06,261 --> 01:58:07,662
EXAMPLE, ONE OF THE THINGS 

2647
01:58:07,662 --> 01:58:08,997
THAT'S VERY, VERY DIFFICULT TO 

2648
01:58:08,997 --> 01:58:10,532
CHARACTERIZE IS WHAT IS THE 

2649
01:58:10,532 --> 01:58:11,633
PATIENT ENVIRONMENT THAT YOU'RE 

2650
01:58:11,633 --> 01:58:15,737
TAKING THESE INNOVATIONS INTO?  

2651
01:58:15,737 --> 01:58:19,241
AND ONE SIZE WILL ABSOLUTELY NOT

2652
01:58:19,241 --> 01:58:20,776
FIT ALL SO WE HAVE TO BE ABLE TO

2653
01:58:20,776 --> 01:58:22,377
TWEAK WHAT WE HAVE GOT AND GET 

2654
01:58:22,377 --> 01:58:24,413
ALL OF THE PARTS OF THE SYSTEM 

2655
01:58:24,413 --> 01:58:25,680
COMFORTABLE AND W THE IDEA THAT 

2656
01:58:25,680 --> 01:58:27,416
WE'RE GOING TO BE LOOKING AT 

2657
01:58:27,416 --> 01:58:28,417
RAKES. 

2658
01:58:28,417 --> 01:58:30,118
NOT NECESSARILY THESE SINGLE 

2659
01:58:30,118 --> 01:58:32,154
WELL, WELL, WELL CHARACTERIZED 

2660
01:58:32,154 --> 01:58:33,555
PRODUCTS AND ONE OF THE WAYS TO 

2661
01:58:33,555 --> 01:58:35,791
GET AT THAT IS IF WE CAN MODEL 

2662
01:58:35,791 --> 01:58:37,359
THE PATIENT ENVIRONMENT BETTER 

2663
01:58:37,359 --> 01:58:39,227
AND A TISSUE CHIP MODEL THAT'S 

2664
01:58:39,227 --> 01:58:40,896
CAREFULLY DESIGNED CAN DO THINGS

2665
01:58:40,896 --> 01:58:43,598
LIKE TITRATE THE AMOUNT OF 

2666
01:58:43,598 --> 01:58:44,833
FIBROSIS THAT'S IN THERE.  

2667
01:58:44,833 --> 01:58:46,835
TITRATE SOME OTHER THINGS SO IN 

2668
01:58:46,835 --> 01:58:47,736
COMBINATION WITH SOME OF THESE 

2669
01:58:47,736 --> 01:58:50,906
ANIMAL MODELS I THINK THEY COULD

2670
01:58:50,906 --> 01:58:52,841
BE BETTER USED THAN IT'S BEING 

2671
01:58:52,841 --> 01:58:54,876
RIGHT NOW SO GO OUT THERE AND 

2672
01:58:54,876 --> 01:58:55,243
COLLABORATE.

2673
01:58:55,243 --> 01:58:58,580
>> YEP.  I TOTALLY AGREE. 
SO 

2674
01:58:58,580 --> 01:59:01,950
BASICALLY WHAT ROSEMARY 

2675
01:59:01,950 --> 01:59:05,554
MENTIONED IS THE CATS TISSUE 

2676
01:59:05,554 --> 01:59:07,956
CHIP PROGRAM IF YOU GOOGLE -- 

2677
01:59:07,956 --> 01:59:10,058
YOU WILL SEE MULTIPLE.  IT'S 

2678
01:59:10,058 --> 01:59:11,960
OVER TEN YEARS OF FUNDING AND 

2679
01:59:11,960 --> 01:59:15,931
THEN ONE OF THE OUTCOME WHERE 

2680
01:59:15,931 --> 01:59:20,202
THE CONSEQUENCE OF THAT IS THE 

2681
01:59:20,202 --> 01:59:21,703
COMPLEMENTARY VISION WHICH, 

2682
01:59:21,703 --> 01:59:23,138
RIGHT, IT'S CORRECT, IT'S NOT 

2683
01:59:23,138 --> 01:59:25,240
GOING TO REPLACE ANIMAL MODEL 

2684
01:59:25,240 --> 01:59:26,675
WHICH IS THE REASON I ACTUALLY 

2685
01:59:26,675 --> 01:59:28,710
USE COMPLEMENTARY.  I THINK YOU 

2686
01:59:28,710 --> 01:59:31,179
HAVE A COMMENT?  YEAH AND THEN 

2687
01:59:31,179 --> 01:59:33,515
WE ARE, YEAH, LAST ONE.  WE ARE 

2688
01:59:33,515 --> 01:59:35,650
GOING TO WRAP UP GOING TO 

2689
01:59:35,650 --> 01:59:35,884
BREAKS.

2690
01:59:35,884 --> 01:59:37,018
>> ONE OF THE COMMENTS
THAT WERE

2691
01:59:37,018 --> 01:59:39,087
MADE EARLIER THAT THESE LARGE 

2692
01:59:39,087 --> 01:59:41,456
ANIMAL STUDIES INVOLVE A LOT OF 

2693
01:59:41,456 --> 01:59:43,959
MONEY.  15,000 DOLLARS PER 

2694
01:59:43,959 --> 01:59:44,926
ANIMAL, SOMETIMES MORE.  WHILE 

2695
01:59:44,926 --> 01:59:46,928
CLINICAL PATIENTS ARE TRIPLE 

2696
01:59:46,928 --> 01:59:49,030
THAT OR QUADRUPLE THAT.  THERE 

2697
01:59:49,030 --> 01:59:49,965
MIGHT BE AN OPPORTUNITY IN A 

2698
01:59:49,965 --> 01:59:54,369
ROLLING WAY FOR THE NIH TO 

2699
01:59:54,369 --> 01:59:55,270
IMPART THEMSELVES AND APPROACH 

2700
01:59:55,270 --> 01:59:56,538
THESE COMPANIES OF WHEN YOU'RE 

2701
01:59:56,538 --> 01:59:58,140
STARTING YOUR PHASE ONE, PHASE 

2702
01:59:58,140 --> 02:00:00,675
TWO CAN WE GET TO SOME OF THE 

2703
02:00:00,675 --> 02:00:02,477
ANSWERS OF THE MORE BASIC 

2704
02:00:02,477 --> 02:00:04,146
SCIENTIFIC QUESTIONS.  BECAUSE 

2705
02:00:04,146 --> 02:00:06,481
THESE COMPANIES THERE ARE 

2706
02:00:06,481 --> 02:00:07,549
BEHOLDEN TO THEIR INVESTORS AND 

2707
02:00:07,549 --> 02:00:08,450
SHARE HOLDERS AND THEY DON'T 

2708
02:00:08,450 --> 02:00:10,919
HAVE UNLIMITED FUNDING TO BE 

2709
02:00:10,919 --> 02:00:12,120
ABLE TO DO THE KIND OF SCIENCE 

2710
02:00:12,120 --> 02:00:13,588
THAT WE'D LIKE. 

2711
02:00:13,588 --> 02:00:15,190
AND I GUESS THE QUID PRO QUO 

2712
02:00:15,190 --> 02:00:16,758
THERE WOULD BE THAT THAT DATA IS

2713
02:00:16,758 --> 02:00:23,165
NOW AVAILABLE TO OTHER INVAES 

2714
02:00:23,165 --> 02:00:24,933
 -- INVESTIGATORS. 

2715
02:00:24,933 --> 02:00:26,434
THESE TRIALS WHEN THEY START 

2716
02:00:26,434 --> 02:00:27,702
THEY WANT TO GO.  YOU KNOW.  I 

2717
02:00:27,702 --> 02:00:29,137
THINK YOU HAVE TO HAVE IT KIND 

2718
02:00:29,137 --> 02:00:31,339
OF A ROLLING OR SOMETHING THAT 

2719
02:00:31,339 --> 02:00:34,643
IS AVAILABLE TO THEM QUICKLY.

2720
02:00:34,643 --> 02:00:36,878
>> THANK YOU.  SO WE ARE
GOING 

2721
02:00:36,878 --> 02:00:39,181
TO GO INTO A FIFTEEN MINUTES 

2722
02:00:39,181 --> 02:00:40,448
BREAK.  THANK YOU VERY MUCH FOR 

2723
02:00:40,448 --> 02:00:42,584
THE SPEAKERS AND THE 

2724
02:00:42,584 --> 02:00:44,119
PARTICIPANTS.  LET'S GIVE US A 

2725
02:00:44,119 --> 02:00:49,257
ROUND OF APPLAUSE.  THANK YOU.  

2726
02:00:49,257 --> 02:00:50,443
THANK YOU.

2727
02:00:51,482 --> 02:00:54,084
SO WE'RE GOING TO
FOLLOW THE 

2728
02:00:54,084 --> 02:00:56,186
SAME FORMAT AS THE FIRST 

2729
02:00:56,186 --> 02:00:58,856
SESSION.  MY CO-MODERATOR IS 

2730
02:00:58,856 --> 02:01:00,157
SITTING RIGHT IN THE FRONT.  

2731
02:01:00,157 --> 02:01:01,625
MARTHA WILL BE HOLDING UP THE 

2732
02:01:01,625 --> 02:01:06,730
ONE MINUTE TO GO SIGN SO IF 

2733
02:01:06,730 --> 02:01:13,570
YOU'RE RUNNING A LITTLE BIT OVER

2734
02:01:13,570 --> 02:01:17,608
SHE WILL BE LETTING YOU KNOW.  I

2735
02:01:17,608 --> 02:01:20,477
THROUGH THE FIRST ACT WAS GREAT.

2736
02:01:20,477 --> 02:01:21,378
THERE'S THE CHALLENGE TO STICK 

2737
02:01:21,378 --> 02:01:25,215
TO YOUR TIME AS BEST YOU CAN.  

2738
02:01:25,215 --> 02:01:30,487
FIRST UP WE CONSTANCE SHEW AND 

2739
02:01:30,487 --> 02:01:31,455
ON DECK.

2740
02:01:31,455 --> 02:01:34,925
 THANK YOU, MAY I HAVE
MY 

2741
02:01:34,925 --> 02:01:36,189
SLIDES, PLEASE?

2742
02:01:40,438 --> 02:01:42,540
THANK YOU FOR THIS 

2743
02:01:42,540 --> 02:01:44,809
OPPORTUNITY TO TALK ABOUT SOME 

2744
02:01:44,809 --> 02:01:47,411
OF THE WORK THAT WAS ACTUALLY 

2745
02:01:47,411 --> 02:01:49,280
FUNDED WITH THE AMERICAN 

2746
02:01:49,280 --> 02:01:51,249
RECOVERY ACT THE ARA FUNDS AND 

2747
02:01:51,249 --> 02:01:55,186
SO IF WE COULD HAVE THE NEXT 

2748
02:01:55,186 --> 02:01:57,855
SLIDE, PLEASE?  SO AS AN 

2749
02:01:57,855 --> 02:01:59,757
ORTHOPEDIC SURGEON I TREAT 

2750
02:01:59,757 --> 02:02:03,628
ARTICULAR CARTILAGE DEFECTS AND 

2751
02:02:03,628 --> 02:02:05,263
ARTICULAR CARTILAGE IS ONE OF 

2752
02:02:05,263 --> 02:02:06,998
THE TISSUES THAT DOESN'T HEAL 

2753
02:02:06,998 --> 02:02:08,366
WELL OR REGENERATE ITSELF.  

2754
02:02:08,366 --> 02:02:11,636
THERE'S NOT A POINTER THAT I CAN

2755
02:02:11,636 --> 02:02:13,671
SEE BUT ON THE LEFT-HAND SIDE 

2756
02:02:13,671 --> 02:02:19,443
BACK TO THE LAST SLIDE, PLEASE. 

2757
02:02:19,443 --> 02:02:21,646
AND SO THROUGH THIS FUNDING WE 

2758
02:02:21,646 --> 02:02:24,549
DID TWO RANDOMIZED CONTROL 

2759
02:02:24,549 --> 02:02:26,851
TRIALS IN HORSES.  AND SO IN 

2760
02:02:26,851 --> 02:02:28,686
THIS INSTANCE, IF YOU LOOK ON 

2761
02:02:28,686 --> 02:02:30,688
THE LEFT-HAND SIDE, THAT IS A 

2762
02:02:30,688 --> 02:02:33,891
CARTILAGE DEFECT.  SO IT'S A 

2763
02:02:33,891 --> 02:02:36,460
POTHOLE IN THE JOINT CARTILAGE, 

2764
02:02:36,460 --> 02:02:38,796
THESE PATIENTS DON'T HAVE 

2765
02:02:38,796 --> 02:02:40,598
OSTEOARTHRITIS BUT IF THESE 

2766
02:02:40,598 --> 02:02:42,767
POTHOLES AREN'T FILLED THEN 

2767
02:02:42,767 --> 02:02:44,035
EVENTUALLY THE PATIENT DOES 

2768
02:02:44,035 --> 02:02:50,408
DEVELOP OSTEOARTHRITIS SO YOU 

2769
02:02:50,408 --> 02:02:52,710
CAN SEE THE HUMAN PATIENT ON THE

2770
02:02:52,710 --> 02:02:54,345
LEFT AND THEN YOU CAN SEE 

2771
02:02:54,345 --> 02:02:57,615
HORSES.  SO USING A GREAT ANIMAL

2772
02:02:57,615 --> 02:03:01,218
MODEL FOR THIS, WE USED BONE 

2773
02:03:01,218 --> 02:03:02,887
MARROW CONCENTRATE TO TREAT ONE 

2774
02:03:02,887 --> 02:03:05,356
OF THE DEFECTS AND SO YOU 

2775
02:03:05,356 --> 02:03:07,992
ALREADY HEARD ABOUT BONE HARROW 

2776
02:03:07,992 --> 02:03:14,131
ASPIRATE CONCENTRATE FROM JOHNNY

2777
02:03:14,131 --> 02:03:16,867
AND BY THE TIME WE DID THIS 

2778
02:03:16,867 --> 02:03:18,536
STUDY THIS WAS CONSIDERED THE 

2779
02:03:18,536 --> 02:03:20,471
CLINICAL STANDARD BY WHICH THE 

2780
02:03:20,471 --> 02:03:22,540
THERAPIES NEEDED TO BE COMPARED 

2781
02:03:22,540 --> 02:03:24,775
TO.  SOME OF THE CHALLENGES WITH

2782
02:03:24,775 --> 02:03:27,612
MICRO FRACTURE INVOLVED DAMAGE 

2783
02:03:27,612 --> 02:03:29,614
TO THE SUB CON JULY BONE SO 

2784
02:03:29,614 --> 02:03:32,249
WE'RE MAKING TINY HOLES IN THE 

2785
02:03:32,249 --> 02:03:33,851
BONES SO THAT THE BONE MARROW 

2786
02:03:33,851 --> 02:03:37,922
CAN COME UP AND FILL THAT 

2787
02:03:37,922 --> 02:03:40,491
CARTILAGE DEFECT AND ESSENTIALLY

2788
02:03:40,491 --> 02:03:42,727
HEAL AND SO OUR STRATEGY WAS TO 

2789
02:03:42,727 --> 02:03:44,695
DIRECTLIES A PLACE THE BONE 

2790
02:03:44,695 --> 02:03:47,465
MARROW CELLS FROM THE BONE 

2791
02:03:47,465 --> 02:03:48,165
MARROW. 

2792
02:03:48,165 --> 02:03:49,467
CONCENTRATE THEM AND PUT THEM 

2793
02:03:49,467 --> 02:03:53,237
INTO THE DEFECT WITHOUT 

2794
02:03:53,237 --> 02:03:55,006
PERFORMING A MICRO FRACTURE SO 

2795
02:03:55,006 --> 02:03:57,908
WITHOUT DAMAGING THE SUB CON 

2796
02:03:57,908 --> 02:04:01,646
DROLL BONE AND WE DID SHOW THAT 

2797
02:04:01,646 --> 02:04:04,915
THESE BONE CONCENTRATE REPAIRS 

2798
02:04:04,915 --> 02:04:06,550
HAD BETTER BONE CHARACTERISTICS 

2799
02:04:06,550 --> 02:04:09,887
AND BETTER CARTILAGE TEXTURAL 

2800
02:04:09,887 --> 02:04:10,554
FEATURES THAN MICRO FRACTURE SO 

2801
02:04:10,554 --> 02:04:13,090
THIS WAS A POSITIVE IN THIS 

2802
02:04:13,090 --> 02:04:14,825
RANDOMIZED CONTROL TRIAL FOR THE

2803
02:04:14,825 --> 02:04:15,793
CELL THERAPY. 

2804
02:04:15,793 --> 02:04:21,632
AND NOW QUICKLY MOVE ONTO THE 

2805
02:04:21,632 --> 02:04:24,468
NEXT STUDY.  THE FIRST ONE WAS 

2806
02:04:24,468 --> 02:04:27,171
DONE WITH LISA IN CORNELL AND 

2807
02:04:27,171 --> 02:04:31,242
THE NEXT AT CSU AND HERE WE 

2808
02:04:31,242 --> 02:04:34,278
COMPARED CULTURE EXPANDED BONE 

2809
02:04:34,278 --> 02:04:42,353
HARROW CELL SEEDED FIBRIN 

2810
02:04:42,353 --> 02:04:44,955
SCAFFOLD WITH THE CELL FREE 

2811
02:04:44,955 --> 02:04:47,658
CONTROLLED SCAFFOLD AND THIS 

2812
02:04:47,658 --> 02:04:48,225
SHOWED THAT THE CELL FREE 

2813
02:04:48,225 --> 02:04:49,727
SCAFFOLD PERFORMED BETTER, HAD 

2814
02:04:49,727 --> 02:04:53,998
MORE CONSISTENT REPAIRS, THE 

2815
02:04:53,998 --> 02:04:55,599
QUANTITATIVE IMAGING WAS 

2816
02:04:55,599 --> 02:04:57,835
PROIMPROVED AND WE DIDN'T HAVE 

2817
02:04:57,835 --> 02:05:00,638
ATOPIC BONE FORMATION WHICH WE 

2818
02:05:00,638 --> 02:05:03,507
DID SEE IN THE FOUR CELL SEEDED 

2819
02:05:03,507 --> 02:05:05,776
REPAIRS AND SO LET'S MOVE ONTO 

2820
02:05:05,776 --> 02:05:07,378
THE NEXT SLIDE AND SO 

2821
02:05:07,378 --> 02:05:11,482
ESSENTIALLY OUR ACADEMIC 

2822
02:05:11,482 --> 02:05:14,552
FINDINGS WITH RNA FINDING WAS WE

2823
02:05:14,552 --> 02:05:16,287
HAD SINGLE STEP PROCEDURES.  

2824
02:05:16,287 --> 02:05:19,857
THAT IN THE FIRST INSTANCE IN 

2825
02:05:19,857 --> 02:05:23,394
DIRECT COMPARISON WITH MICRO 

2826
02:05:23,394 --> 02:05:24,795
FRACTURE THE REPAIRS WERE 

2827
02:05:24,795 --> 02:05:26,530
SUPERIOR AND IN THE SECOND 

2828
02:05:26,530 --> 02:05:27,665
INSTANCE WE HAD A CELL FREE 

2829
02:05:27,665 --> 02:05:30,701
SCOFF FOLD THAT IF WE COMPARED 

2830
02:05:30,701 --> 02:05:32,303
THE HISTOLOGY AND THE 

2831
02:05:32,303 --> 02:05:34,672
QUANTITATIVE MR SO WE USED THE 

2832
02:05:34,672 --> 02:05:37,341
SAME QUANTITATIVE MR THAT I USE 

2833
02:05:37,341 --> 02:05:40,745
IN MY HUMAN PATIENTS I THINK THE

2834
02:05:40,745 --> 02:05:42,913
APF EF REPAIR WAS SIMILARLY 

2835
02:05:42,913 --> 02:05:46,016
GOOD, POSSIBLY A LITTLE BIT 

2836
02:05:46,016 --> 02:05:49,086
BETTER.  AND SO WHAT HAPPENED?  

2837
02:05:49,086 --> 02:05:50,888
WHY DID THESE NOT PROGRESS.  

2838
02:05:50,888 --> 02:05:54,825
WELL I TERM THEM ORPHAN BECAUSE 

2839
02:05:54,825 --> 02:05:57,828
IN THIS SAME TIME PERIOD, THERE 

2840
02:05:57,828 --> 02:06:03,667
WERE TRIALS GOING ON FOR 

2841
02:06:03,667 --> 02:06:06,370
NEOCART.  THE MACY WAS COMING 

2842
02:06:06,370 --> 02:06:10,307
INTO FRUITION FROM MULTICENTERED

2843
02:06:10,307 --> 02:06:15,846
TRIALS AND THESE SIMPLY WEREN'T 

2844
02:06:15,846 --> 02:06:16,547
CONSIDERED INNOVATIVE CELL 

2845
02:06:16,547 --> 02:06:19,083
THERAP

2846
02:06:19,083 --> 02:06:20,084
THERAPIES.  THERE WAS ALSO 

2847
02:06:20,084 --> 02:06:22,820
THE -- WE COULD NOT GET INDUSTRY

2848
02:06:22,820 --> 02:06:23,754
INTERESTED.  THE PEOPLE WHO DID 

2849
02:06:23,754 --> 02:06:25,689
THE BONE MARROW CONCENTRATES 

2850
02:06:25,689 --> 02:06:28,559
BECAUSE THE COMMENT WAS, WELL, 

2851
02:06:28,559 --> 02:06:30,628
YOU CAN JUST DO THIS WITHOUT 

2852
02:06:30,628 --> 02:06:35,166
FURTHER RESEARCH.  AND IN MIND 

2853
02:06:35,166 --> 02:06:36,834
WHAT I THOUGHT WAS THIS NEEDED 

2854
02:06:36,834 --> 02:06:40,104
AT LEAST A RANDOMIZED CONTROL 

2855
02:06:40,104 --> 02:06:41,605
TRIAL IN HUMAN PATIENTS TO DO A 

2856
02:06:41,605 --> 02:06:44,375
WELL CONDUCTED STUDY.  GET OUR 

2857
02:06:44,375 --> 02:06:45,609
QUANTITATIVE ASSESSMENTS AND 

2858
02:06:45,609 --> 02:06:49,180
REALLY SEE WHERE THIS STANDS IN 

2859
02:06:49,180 --> 02:06:53,317
HUMANS.  AND IT SIMPLY HAD -- WE

2860
02:06:53,317 --> 02:06:56,320
FELL INTO THIS GAP.  THERE WAS 

2861
02:06:56,320 --> 02:06:59,790
NOT INDUSTRY INTEREST.  FROM A 

2862
02:06:59,790 --> 02:07:02,493
REVIEW PANEL STANDPOINT.  IT WAS

2863
02:07:02,493 --> 02:07:04,195
CONSIDERED MAYBE NOT THAT 

2864
02:07:04,195 --> 02:07:08,098
INTERESTING AND ALSO AMONG MY 

2865
02:07:08,098 --> 02:07:09,333
COLLEAGUES.  SO THESE CON DROLL 

2866
02:07:09,333 --> 02:07:10,701
DEFECTS ARE NOT SO COMMON THAT 

2867
02:07:10,701 --> 02:07:13,103
YOU CAN DO A GOOD RANDOMIZED 

2868
02:07:13,103 --> 02:07:14,572
CONTROL TRIAL IN A SINGLE 

2869
02:07:14,572 --> 02:07:14,939
CENTER. 

2870
02:07:14,939 --> 02:07:16,907
YOU NEED TO HAVE MULTICENTER 

2871
02:07:16,907 --> 02:07:20,544
STUDIES AND OTHERS WERE ALREADY 

2872
02:07:20,544 --> 02:07:23,781
INVOLVED IN NEOCART OR SOME 

2873
02:07:23,781 --> 02:07:26,617
OTHER STUDIES.  AND SO THE 

2874
02:07:26,617 --> 02:07:28,219
THINKING THAT I HAVE IS THAT IF 

2875
02:07:28,219 --> 02:07:32,556
THERE'S AN NIH FUNDED STUDY. 

2876
02:07:32,556 --> 02:07:34,325
THERE PROBABLY SHOULD BE A 

2877
02:07:34,325 --> 02:07:37,761
REVIEW AND IT SHOULD BE A -- 

2878
02:07:37,761 --> 02:07:42,066
WITH THE FDA AND OTHER FEDERAL 

2879
02:07:42,066 --> 02:07:43,133
AGENCIES.  WHAT'S THE NEXT STEP 

2880
02:07:43,133 --> 02:07:45,469
FOR THIS?  IS THIS ONE -- GOOD 

2881
02:07:45,469 --> 02:07:47,238
ENOUGH?  IS THIS ANIMAL DATA 

2882
02:07:47,238 --> 02:07:49,440
LARGE ANIMAL STUDY GOOD ENOUGH 

2883
02:07:49,440 --> 02:07:51,408
FOR CLINICAL IMPLEMENTATION?  

2884
02:07:51,408 --> 02:07:53,210
LIKE I WAS BEING TOLD BY 

2885
02:07:53,210 --> 02:07:54,912
INDUSTRY OR DOES IT NEED ANOTHER

2886
02:07:54,912 --> 02:07:57,414
STUDY AND IF SO, WHAT DOES IT 

2887
02:07:57,414 --> 02:08:00,117
NEED?  ALSO, IT'S ALREADY BEEN 

2888
02:08:00,117 --> 02:08:02,119
MENTIONED FDA PARTNERSHIP AND 

2889
02:08:02,119 --> 02:08:05,089
DEVELOPING CLINICAL TRIAL 

2890
02:08:05,089 --> 02:08:07,124
STANDARDS EARLY ON.  CLINICAL 

2891
02:08:07,124 --> 02:08:09,894
OUTCOMES EVALUATION AND THIS IS 

2892
02:08:09,894 --> 02:08:13,097
A CONTINUOUS PROCESS.  SO EVERY 

2893
02:08:13,097 --> 02:08:15,065
RANDOMIZED CONTROL TRIAL DONE IN

2894
02:08:15,065 --> 02:08:17,368
EACH OF OUR DISEASE STATES, WE 

2895
02:08:17,368 --> 02:08:20,237
LEARN FROM IT.  VALUABLE 

2896
02:08:20,237 --> 02:08:21,906
INFORMATION THAT'S USEFUL FOR 

2897
02:08:21,906 --> 02:08:24,308
THE NEXT STEP.  AND MANY TIMES 

2898
02:08:24,308 --> 02:08:27,244
IT'S LOST BECAUSE ONE IS 

2899
02:08:27,244 --> 02:08:28,345
CONDUCTED BY ONE COMPANY THAT 

2900
02:08:28,345 --> 02:08:31,916
COMPANY GOES OUT OF BUSINESS OR 

2901
02:08:31,916 --> 02:08:33,250
THERE ARE TRADE SECRETS, THINGS 

2902
02:08:33,250 --> 02:08:37,721
THAT AREN'T SHARED AND SO MY 

2903
02:08:37,721 --> 02:08:41,191
RADICAL IDEA IS THAT THIS MAY 

2904
02:08:41,191 --> 02:08:45,896
NOT BE -- NEXT -- CLICK ON THE 

2905
02:08:45,896 --> 02:08:49,833
THIS MAY NOT BE THE DIRECT 

2906
02:08:49,833 --> 02:08:51,468
VERSION IS PERHAPS THESE EARLY 

2907
02:08:51,468 --> 02:08:53,637
STAGE CLINICAL TRIALS COULD BE 

2908
02:08:53,637 --> 02:08:57,875
DONE AT THE NIH CLINICAL CENTER 

2909
02:08:57,875 --> 02:09:00,544
OR IN COLLABORATION MAYBE WITH 

2910
02:09:00,544 --> 02:09:03,380
THE BETHESDA MILITARY MEDICAL 

2911
02:09:03,380 --> 02:09:05,616
CENTER AND YOU'RE GOING TO LEARN

2912
02:09:05,616 --> 02:09:08,452
WHAT'S IMPORTANT IN THIS SPACE. 

2913
02:09:08,452 --> 02:09:09,720
FOR THAT CLINICAL TRIAL.  WHAT 

2914
02:09:09,720 --> 02:09:13,524
ARE SOME OF THE PITFALLS AND 

2915
02:09:13,524 --> 02:09:16,060
YOU'LL ALSO HAVE SOME 

2916
02:09:16,060 --> 02:09:16,827
INSTITUTIONAL KNOWLEDGE.  SO ONE

2917
02:09:16,827 --> 02:09:20,631
OF THE STUDIES I MENTIONED IN 

2918
02:09:20,631 --> 02:09:23,100
NEOCART ACTUALLY WAS STOPPED 

2919
02:09:23,100 --> 02:09:25,469
EARLY.  BECAUSE THE MICRO 

2920
02:09:25,469 --> 02:09:29,173
FRACTURE THAT I MENTIONED THAT 

2921
02:09:29,173 --> 02:09:32,710
OUR BONE MARROW CONCENTRATE 

2922
02:09:32,710 --> 02:09:37,014
WAS -- WAS IMPROVED OVER THE 

2923
02:09:37,014 --> 02:09:38,716
MICRO FRACTURE OUTPERFORMS SO 

2924
02:09:38,716 --> 02:09:40,584
THEY DIDN'T SHOW SUFFICIENT 

2925
02:09:40,584 --> 02:09:42,953
IMPROVEMENT AT ONE YEAR ABOVE 

2926
02:09:42,953 --> 02:09:43,320
MICRO FRACTURE. 

2927
02:09:43,320 --> 02:09:45,289
BUT THEN ALL THOSE PATIENTS HAVE

2928
02:09:45,289 --> 02:09:48,258
BEEN LOST.  SO NOW WE'RE GETTING

2929
02:09:48,258 --> 02:09:50,427
FIVE TO TEN YEARS FROM WHEN 

2930
02:09:50,427 --> 02:09:53,864
THOSE PATIENTS WERE FIRST 

2931
02:09:53,864 --> 02:09:55,766
IMPLANTED IN THE PHASE TWO TRIAL

2932
02:09:55,766 --> 02:09:57,634
AND IT WOULD BE EXTREMELY 

2933
02:09:57,634 --> 02:09:59,703
VALUABLE IF THOSE PATIENTS COULD

2934
02:09:59,703 --> 02:10:01,772
ACTUALLY BE BROUGHT BACK.  FOR A

2935
02:10:01,772 --> 02:10:05,542
LONGER TERM FOLLOW-UP SO THANK 

2936
02:10:05,542 --> 02:10:15,986
YOU FOR YOUR PATIENCE.  .

2937
02:10:25,629 --> 02:10:28,932
>> THANK YOU FOR HAVING
ME.  

2938
02:10:28,932 --> 02:10:33,337
THIS IS A GREAT FORUM.  TIM CAMP

2939
02:10:33,337 --> 02:10:36,173
EMBARKED ON THIS RMIP PROJECT 

2940
02:10:36,173 --> 02:10:37,875
AND TIM HIGHLIGHTED IT QUITE 

2941
02:10:37,875 --> 02:10:39,910
NICELY ALREADY.  I ALSO CONSULT 

2942
02:10:39,910 --> 02:10:41,345
FOR A NUMBER OF COMPANIES 

2943
02:10:41,345 --> 02:10:43,113
ACTIVELY AND I'VE BEEN INVOLVED 

2944
02:10:43,113 --> 02:10:45,082
WITH OVER A DOZEN CLINICAL 

2945
02:10:45,082 --> 02:10:46,784
TRIALS AND IN THE CARDIOVASCULAR

2946
02:10:46,784 --> 02:10:48,585
SPACE OVER THE LAST TWENTY YEARS

2947
02:10:48,585 --> 02:10:50,721
OR SO RELATED TO CELL BASED 

2948
02:10:50,721 --> 02:10:54,391
THERAPY SO WHAT I'M GOING TO SAY

2949
02:10:54,391 --> 02:11:01,331
IS PART OF THAT.  THERE WE GO.  

2950
02:11:01,331 --> 02:11:03,400
ALL RIGHT.  SO IN TERMS OF 

2951
02:11:03,400 --> 02:11:05,569
CHALLENGES THAT WE FACE IN THE 

2952
02:11:05,569 --> 02:11:06,336
FIELDS OF CARDIOVASCULAR THERAPY

2953
02:11:06,336 --> 02:11:08,505
AND I AM TRYING TO THINK ABOUT 

2954
02:11:08,505 --> 02:11:11,942
IT IN HOLISTIC TERMS IN HOW WE 

2955
02:11:11,942 --> 02:11:13,844
CAN AFFECT MULTIPLE DIFFERENT 

2956
02:11:13,844 --> 02:11:15,045
SPECIALTIES AND SO FORTH.  I 

2957
02:11:15,045 --> 02:11:18,048
THINK ONE OF THE THINGS THAT -- 

2958
02:11:18,048 --> 02:11:19,750
AND IT'S DIFFICULT TO PRIORITIZE

2959
02:11:19,750 --> 02:11:20,951
WHAT'S MORE IMPORTANT THAN 

2960
02:11:20,951 --> 02:11:22,052
OTHERS.  I HAD A DIFFERENT TIME 

2961
02:11:22,052 --> 02:11:25,022
WITH THAT BUT I WANTED TO 

2962
02:11:25,022 --> 02:11:26,390
EMPHASIZE CELL DELIVERY.  I 

2963
02:11:26,390 --> 02:11:28,725
THINK IT'S OFTEN OVERLOOKED.  

2964
02:11:28,725 --> 02:11:30,327
YES, WE DO NEED IMPORTANT 

2965
02:11:30,327 --> 02:11:30,994
ADVANCES IN CLINICAL GRADE 

2966
02:11:30,994 --> 02:11:32,963
MANUFACTURING TO MAKE IT 

2967
02:11:32,963 --> 02:11:34,098
ACCESSIBLE TO SMALL START-UP 

2968
02:11:34,098 --> 02:11:37,468
COMPANIES OR ACADEMIC 

2969
02:11:37,468 --> 02:11:40,571
INSTITUTIONS.  WE NEED A 

2970
02:11:40,571 --> 02:11:41,705
CLINICAL TRIALS INFRASTRUCTURE, 

2971
02:11:41,705 --> 02:11:42,940
YES, WE NEED THAT AS WELL.  I 

2972
02:11:42,940 --> 02:11:44,741
THINK ONE OF THE THINGS I 

2973
02:11:44,741 --> 02:11:45,976
OBSERVED IS I WAS JUST TALKING 

2974
02:11:45,976 --> 02:11:47,878
EARLIER IN THE BREAK, YOU KNOW, 

2975
02:11:47,878 --> 02:11:50,481
A LOT OF ACADEMIC INSTITUTIONS 

2976
02:11:50,481 --> 02:11:56,487
DEVELOP A CELL THERAPY PRODUCT, 

2977
02:11:56,487 --> 02:11:57,855
GETS IT THROUGH THINKING ABOUT 

2978
02:11:57,855 --> 02:12:00,224
ALL THE POTENCY DISCUSSION AND 

2979
02:12:00,224 --> 02:12:01,058
THEN ALL OF A SUDDEN OKAY NOW 

2980
02:12:01,058 --> 02:12:02,459
IT'S TIME TO DELIVER IT IN A 

2981
02:12:02,459 --> 02:12:04,428
PATIENT AND WE'RE AT A ROADBLOCK

2982
02:12:04,428 --> 02:12:06,230
BECAUSE WE DON'T HAVE THE TOOLS 

2983
02:12:06,230 --> 02:12:09,366
NECESSARY TO DELIVER THAT IN A 

2984
02:12:09,366 --> 02:12:15,305
PATIENT YET.  CROSSCUTTING, YOU 

2985
02:12:15,305 --> 02:12:17,608
KNOW, OPPORTUNITIES TO TRY TO 

2986
02:12:17,608 --> 02:12:19,209
ADDRESS THESE CHALLENGES I 

2987
02:12:19,209 --> 02:12:21,211
THINK, YOU KNOW, IF WE COULD -- 

2988
02:12:21,211 --> 02:12:22,946
GET INVESTMENT INTO THINKING 

2989
02:12:22,946 --> 02:12:24,615
ABOUT, OKAY, HOW CAN WE DELIVER 

2990
02:12:24,615 --> 02:12:27,184
THESE CELLS TO THEIR TARGET 

2991
02:12:27,184 --> 02:12:29,219
ORGANS?  HOW DO WE DO THIS 

2992
02:12:29,219 --> 02:12:35,492
MINIMALLY INVEINOVATVEIASIVE AN 

2993
02:12:35,492 --> 02:12:37,327
ABOUT MAXIMUM LOCAL CELL 

2994
02:12:37,327 --> 02:12:40,397
RETENTION AND HOW IT'S IMPORTANT

2995
02:12:40,397 --> 02:12:45,068
AND THEN OF COURSE THE GRAFTING.

2996
02:12:45,068 --> 02:12:47,137
HOW DO WE GET THE CELLS TO STAY 

2997
02:12:47,137 --> 02:12:49,006
THERE AND THAT WAS PART OF OUR 

2998
02:12:49,006 --> 02:12:51,642
RMIP INITIATIVE.  THE LAST -- 

2999
02:12:51,642 --> 02:12:55,312
THE BOTTOM FOUR FIGURES THERE 

3000
02:12:55,312 --> 02:12:57,781
WERE NOT COVERED BY THE RMIP BUT

3001
02:12:57,781 --> 02:13:00,784
DO HIGHLIGHT WHAT I'M KIND OF 

3002
02:13:00,784 --> 02:13:02,653
GETTING AT.  ON THE LEFT SIDE IS

3003
02:13:02,653 --> 02:13:06,823
A RAT HEART WHERE WE INJECTED 

3004
02:13:06,823 --> 02:13:09,893
STEM CELLS.  ALONGSIDE THE 

3005
02:13:09,893 --> 02:13:13,564
RETENTION MATRIX THAT WE WERE 

3006
02:13:13,564 --> 02:13:14,798
INVESTIGATING.  IN ADDITION, THE

3007
02:13:14,798 --> 02:13:15,933
BLUE IT IS A BIT DIFFICULT TO 

3008
02:13:15,933 --> 02:13:17,668
SEE THERE ARE THE CELLS INJECTED

3009
02:13:17,668 --> 02:13:19,937
WITHOUT THE MATRIX IN THE RAT 

3010
02:13:19,937 --> 02:13:21,438
HEART WITH THE NEEDLE INJECTION,

3011
02:13:21,438 --> 02:13:24,508
THE CELLS THAT HAD THE MATRIX 

3012
02:13:24,508 --> 02:13:25,876
RETAINED IN A LINEAR FASHION 

3013
02:13:25,876 --> 02:13:27,778
WITH A NEEDLE INJECTION WAS THE 

3014
02:13:27,778 --> 02:13:31,014
BLUE CELLS THAT ARE NOW BEING 

3015
02:13:31,014 --> 02:13:33,917
DISPERSED THROUGHOUT THE 

3016
02:13:33,917 --> 02:13:35,452
LYMPHATICS ALL THROUGHOUT BUT 

3017
02:13:35,452 --> 02:13:36,486
OPEN CHEST IN A RAT IS NOT 

3018
02:13:36,486 --> 02:13:38,222
REALLY APPEALING CLINICALLY.  

3019
02:13:38,222 --> 02:13:41,725
HOW DO WE ACHIEVE THAT GOAL OF 

3020
02:13:41,725 --> 02:13:43,260
INTRAMY OWE YARD CALENDAR 

3021
02:13:43,260 --> 02:13:43,560
DELIVERY?

3022
02:13:43,560 --> 02:13:45,529
ALLOWING THE LINE OF TWO OR 

3023
02:13:45,529 --> 02:13:49,066
THREE DIFFERENT CATHETER 

3024
02:13:49,066 --> 02:13:51,134
COMPANIES HAVE DEVELOPED MINIMAL

3025
02:13:51,134 --> 02:13:52,236
STEERABLE CATHETERS THAT WE CAN 

3026
02:13:52,236 --> 02:13:54,504
FEED IN AND INTRODUCE IN THE 

3027
02:13:54,504 --> 02:13:57,441
HEART BUT THESE ARE ALL IDE TYPE

3028
02:13:57,441 --> 02:13:58,976
DEVICES.  THERE'S NOTHING LIKE 

3029
02:13:58,976 --> 02:14:00,544
THAT OUT CURRENTLY.  AND, YOU 

3030
02:14:00,544 --> 02:14:01,511
KNOW, WHEN I WAS INVOLVED WITH 

3031
02:14:01,511 --> 02:14:03,413
CLINICAL TRIALS, YOU KNOW, YOU 

3032
02:14:03,413 --> 02:14:05,549
ENROLLED TWO OR THREE PATIENTS 

3033
02:14:05,549 --> 02:14:06,583
AND THEN ALL OF A SUDDEN YOU 

3034
02:14:06,583 --> 02:14:11,755
BECAME A PROBLCTOR AND YOU GO 

3035
02:14:11,755 --> 02:14:14,124
AROUND TEACHING PEOPLE THESE 

3036
02:14:14,124 --> 02:14:15,192
DEVICES.  THERE'S QUITE A STEEP 

3037
02:14:15,192 --> 02:14:16,660
LEARNING CURVE NOT ONLY IN THE 

3038
02:14:16,660 --> 02:14:17,728
PREPARATION OF THE CELLS BUT 

3039
02:14:17,728 --> 02:14:20,264
ALSO IN THE DELIVERY ASPECT.  

3040
02:14:20,264 --> 02:14:24,268
LOCALLY WE'RE ALSO LOOKING AT 

3041
02:14:24,268 --> 02:14:26,236
WAYS OF DELIVERING THE CELLS IN 

3042
02:14:26,236 --> 02:14:29,840
A TARGETED FASHION BY 

3043
02:14:29,840 --> 02:14:31,241
MULTIMODALITY INFUSION IMAGING 

3044
02:14:31,241 --> 02:14:35,946
WHERE WE CAN SEE THE MRI VISION 

3045
02:14:35,946 --> 02:14:38,982
OF THE HEART.  SO TO FINISH, 

3046
02:14:38,982 --> 02:14:40,417
WHAT ARE THE OPPORTUNITIES THAT 

3047
02:14:40,417 --> 02:14:42,953
WE -- I THINK THAT THE -- THIS 

3048
02:14:42,953 --> 02:14:44,288
GROUP COULD POTENTIALLY DELIVER 

3049
02:14:44,288 --> 02:14:45,889
HERE ON THIS?  I THINK 

3050
02:14:45,889 --> 02:14:47,491
INVESTMENTS IN FIGURING OUT 

3051
02:14:47,491 --> 02:14:49,459
BETTER WAYS OF CELL TRACKING SO 

3052
02:14:49,459 --> 02:14:51,295
WE CAN DO MORE LONGITUDINAL 

3053
02:14:51,295 --> 02:14:54,564
STUDIES, DEVELOPING NEWER, LESS 

3054
02:14:54,564 --> 02:14:56,566
INNOVATIVE DELIVERY TOOLS TO 

3055
02:14:56,566 --> 02:14:58,235
REALLY EMBARK UPON THAT HOLY 

3056
02:14:58,235 --> 02:15:01,605
GRAIL OF BEST CELL RETENTION AND

3057
02:15:01,605 --> 02:15:03,073
ENGRAFTMENT AND THEN TRANSLATING

3058
02:15:03,073 --> 02:15:05,409
THAT IN CLINICALLY TRANSLATABLE 

3059
02:15:05,409 --> 02:15:07,377
MODELS LIKE IN THE PIG, FOR 

3060
02:15:07,377 --> 02:15:08,679
EXAMPLE, AND OUR INSTITUTION HAS

3061
02:15:08,679 --> 02:15:11,181
MADE SOME INVESTMENTS IN THAT, 

3062
02:15:11,181 --> 02:15:13,016
SOME SEED MONEY HAS GONE TOWARD 

3063
02:15:13,016 --> 02:15:17,020
A CENTER FOR BIOMEDICAL SWINE 

3064
02:15:17,020 --> 02:15:20,057
RESEARCH FOR EXAMPLE.  AND THEN 

3065
02:15:20,057 --> 02:15:21,992
ALONG THE WAYS DEVELOPING THE 

3066
02:15:21,992 --> 02:15:23,527
CLINICAL TRIAL NETWORK SO WE CAN

3067
02:15:23,527 --> 02:15:26,830
CONSOLIDATE THE EXPERTISE AND 

3068
02:15:26,830 --> 02:15:30,167
THEN IN A LOW TAG MODEL SEND 

3069
02:15:30,167 --> 02:15:33,670
THAT EXPERTISE OUT AND 

3070
02:15:33,670 --> 02:15:34,938
PROCTORING OTHER PEOPLE TO DO 

3071
02:15:34,938 --> 02:15:38,442
THESE PROCEDURES.  THAT'S IT.  

3072
02:15:38,442 --> 02:15:48,652
THANK YOU.

3073
02:15:51,555 --> 02:15:53,557
>> THANK YOU FOR INVITING
ME TO 

3074
02:15:53,557 --> 02:15:55,592
SPEAK HERE TODAY.  IT'S A REALLY

3075
02:15:55,592 --> 02:15:56,693
WONDERFUL MEETING AND I HOPE TO 

3076
02:15:56,693 --> 02:15:59,596
LEARN A LOT AND MAYBE CONTRIBUTE

3077
02:15:59,596 --> 02:16:03,266
A BIT TO YOURS AS WELL.  WHAT MY

3078
02:16:03,266 --> 02:16:06,136
LAB IS INTERESTED IN IS THE 

3079
02:16:06,136 --> 02:16:07,037
TRANSPORTATION.  IT'S A LARGE 

3080
02:16:07,037 --> 02:16:09,706
NEURON THAT SIT IN THE BACK OF 

3081
02:16:09,706 --> 02:16:14,311
THE EYE IN THE RETINA AND THEIR 

3082
02:16:14,311 --> 02:16:15,912
ACCESS SENDS THE PROJECTIONS AND

3083
02:16:15,912 --> 02:16:17,647
ALL THE INFORMATION TO THE 

3084
02:16:17,647 --> 02:16:19,149
BRAIN.  AND WHAT IS VERY 

3085
02:16:19,149 --> 02:16:20,050
DIFFERENT ABOUT THE RETINA OF 

3086
02:16:20,050 --> 02:16:24,554
THE EYE, THE OPTIC NERVE IN AND 

3087
02:16:24,554 --> 02:16:27,457
OTHER MAMMALS IS IT DOES NOT 

3088
02:16:27,457 --> 02:16:28,658
REGENERATE AFTER THE DEVELOPMENT

3089
02:16:28,658 --> 02:16:30,927
IS COMPLETE.  WHETHER WE EMBARK 

3090
02:16:30,927 --> 02:16:32,396
ON DEVELOPING THE MEDICINE 

3091
02:16:32,396 --> 02:16:33,397
THERAPIES WE HAVE TO COME UP 

3092
02:16:33,397 --> 02:16:38,101
WITH SOME SOLUTIONS THAT EITHER 

3093
02:16:38,101 --> 02:16:40,237
COME UP AS WHOLE TISSUE 

3094
02:16:40,237 --> 02:16:43,640
APPROACH, SOUNDS LIKE RP 

3095
02:16:43,640 --> 02:16:45,242
TRANSPORTATION IF YOU HEARD FROM

3096
02:16:45,242 --> 02:16:46,710
AARON AND JEFFREY OR DO 

3097
02:16:46,710 --> 02:16:48,178
SOMETHING LIKE RETICKULATION OF 

3098
02:16:48,178 --> 02:16:49,579
THE DEVELOPMENT.  THIS IS WHAT 

3099
02:16:49,579 --> 02:16:52,749
WE TRIED TO DO WITH THE GANGLION

3100
02:16:52,749 --> 02:16:53,884
CELL IMPLEMENTATION AND BACK TO 

3101
02:16:53,884 --> 02:16:56,620
THE LIST OF QUESTIONS THAT WE 

3102
02:16:56,620 --> 02:16:58,722
GOT.  WITH THIS INVITATION SO I 

3103
02:16:58,722 --> 02:17:02,759
WOULD SAY, I WILL GO BACK.  

3104
02:17:02,759 --> 02:17:05,629
LET'S TRY THIS ONE.  OH, THANK 

3105
02:17:05,629 --> 02:17:07,964
YOU.  I THINK THIS IS THE FIRST 

3106
02:17:07,964 --> 02:17:09,933
CHALLENGE.  SO THAT'S HOW THE 

3107
02:17:09,933 --> 02:17:11,501
STANDARD CELL LOOK LIKE.  YOU 

3108
02:17:11,501 --> 02:17:15,138
CAN REPLACE THE RETINAL GANGLION

3109
02:17:15,138 --> 02:17:19,209
CELL WHICH IS HERE.  LASER 

3110
02:17:19,209 --> 02:17:28,685
POINTER?  NO?  I THINK REPLACE 

3111
02:17:28,685 --> 02:17:29,886
RETINAL GANGLION CELL WITH ANY 

3112
02:17:29,886 --> 02:17:31,521
OTHER CELL TYPE OF INTEREST BUT 

3113
02:17:31,521 --> 02:17:34,591
THIS IS THE MAIN CHALLENGE.  WE 

3114
02:17:34,591 --> 02:17:36,126
HAVE TO DO EVERYTHING ALL OF 

3115
02:17:36,126 --> 02:17:38,562
THESE STEPS THAT DO TO CELL 

3116
02:17:38,562 --> 02:17:40,564
THERAPY WITHIN ONE LAB.  SO 

3117
02:17:40,564 --> 02:17:42,132
THAT'S WHAT I THINK THE SOLUTION

3118
02:17:42,132 --> 02:17:42,999
IS.  YOU REALLY ADVANCE AND 

3119
02:17:42,999 --> 02:17:48,872
MAUVE  MOVE ON TO BE ABLE TO 

3120
02:17:48,872 --> 02:17:51,908
DELIVER THE FINAL PRODUCT.  THE 

3121
02:17:51,908 --> 02:17:53,810
ACTUAL CELL THERAPY TO REGAIN 

3122
02:17:53,810 --> 02:17:54,778
THEIR VISION. 

3123
02:17:54,778 --> 02:17:57,047
AND THE SECOND CHALLENGE, THAT 

3124
02:17:57,047 --> 02:17:58,682
GOES INTO THIS AND MAKE THESE 

3125
02:17:58,682 --> 02:18:00,584
THINGS CONNECTED IS I LIKE TO 

3126
02:18:00,584 --> 02:18:03,053
THINK ABOUT IS A NUMBERS GAME.  

3127
02:18:03,053 --> 02:18:05,555
SO AT EACH STEP WE NEED TO HAVE 

3128
02:18:05,555 --> 02:18:08,191
SOME DELIVERABLE.  COULD YOU 

3129
02:18:08,191 --> 02:18:11,728
ADVANCE THE SLIDE?  AND WITH 

3130
02:18:11,728 --> 02:18:13,730
RETINAL, COULD YOU ADVANCE THE 

3131
02:18:13,730 --> 02:18:17,067
SLIDE, PLEASE?  ALL RIGHT.  

3132
02:18:17,067 --> 02:18:21,071
THANKS.  AND WITH RETINAL 

3133
02:18:21,071 --> 02:18:22,973
IMPLEMENTATION IF WE INJECT WE 

3134
02:18:22,973 --> 02:18:24,774
NEED ABOUT FIVE THOUSAND CELLS. 

3135
02:18:24,774 --> 02:18:26,209
THAT'S THE MINIMAL NUMBER THAT 

3136
02:18:26,209 --> 02:18:28,512
IS NEEDED TO REGAIN FUNCTIONAL 

3137
02:18:28,512 --> 02:18:30,747
VISION AND AT EACH STEP YOU 

3138
02:18:30,747 --> 02:18:33,083
THINK OF ALL STEPS THAT CELL HAS

3139
02:18:33,083 --> 02:18:34,818
TO DO THROUGH AFTER 

3140
02:18:34,818 --> 02:18:36,086
TRANSPLANTATION HAS SUSTAINED.  

3141
02:18:36,086 --> 02:18:40,357
AT THE SITE OF INJECTION HAS TO 

3142
02:18:40,357 --> 02:18:42,158
MIGRATE TO THE RETINAL GANGLION 

3143
02:18:42,158 --> 02:18:45,061
CELL LAYER, AND TO CONNECT WITH 

3144
02:18:45,061 --> 02:18:49,866
THE ADJACENT NEURONS AND UNDERGO

3145
02:18:49,866 --> 02:18:54,604
FUNCTIONAL MOLECULAR METABOLIC 

3146
02:18:54,604 --> 02:18:56,973
AND AT THE END YOU HAVE THIS.  

3147
02:18:56,973 --> 02:18:58,875
SO AT EACH STEP SOME CELLS ARE 

3148
02:18:58,875 --> 02:19:02,212
LOST AND IDEALLY, AND SOME, FOR 

3149
02:19:02,212 --> 02:19:04,381
EXAMPLE, IF WE INJECT ONE ONLY 

3150
02:19:04,381 --> 02:19:06,983
FIVE THOUSAND CELLS WILL MAKE IT

3151
02:19:06,983 --> 02:19:08,919
AFTER TWO WEEKS SO YOU KNOW THAT

3152
02:19:08,919 --> 02:19:10,287
YOU GET TO THE FINAL NUMBER WE 

3153
02:19:10,287 --> 02:19:12,255
NEED TO GO WITH TRILLIONS BUT 

3154
02:19:12,255 --> 02:19:13,723
OBVIOUSLY THIS IS NOT POSSIBLE 

3155
02:19:13,723 --> 02:19:16,092
SO THIS IS WHERE WE HAVE TO 

3156
02:19:16,092 --> 02:19:18,828
IMPROVE AND THAT'S WHERE SHARING

3157
02:19:18,828 --> 02:19:21,331
INFORMATION, SHARING THE DATA, 

3158
02:19:21,331 --> 02:19:24,834
COMING UP WITH QUANTIFIABLE 

3159
02:19:24,834 --> 02:19:27,003
METRICS FOR EACH OF THESE STEPS 

3160
02:19:27,003 --> 02:19:28,772
THAT CELLS HAS TO GO THROUGH 

3161
02:19:28,772 --> 02:19:31,575
WOULD REALLY HELP TO ADVANCE THE

3162
02:19:31,575 --> 02:19:32,509
FIELD.  AND THIS JUST AN EXAMPLE

3163
02:19:32,509 --> 02:19:34,778
OF HOW WE DO IT IN THE LAB.  SO 

3164
02:19:34,778 --> 02:19:36,313
WE FOCUS ON THE CELLULAR 

3165
02:19:36,313 --> 02:19:38,615
FUNCTION TRYING TO LEARN FROM 

3166
02:19:38,615 --> 02:19:39,883
THE DEVELOPMENT USING SINGLE LAR

3167
02:19:39,883 --> 02:19:41,985
CELL APPROACHES, HOW TO MODIFY 

3168
02:19:41,985 --> 02:19:45,922
THE RETINAL MICRO ENVIRONMENT IN

3169
02:19:45,922 --> 02:19:48,425
ORDER TO SUPPORT DONOR CELLS 

3170
02:19:48,425 --> 02:19:50,894
AFTER TRANSPLANTATION TO CONTROL

3171
02:19:50,894 --> 02:19:53,096
DONOR CELLS AFTER 

3172
02:19:53,096 --> 02:19:54,497
TRANSPLANTATION AND WE TALK 

3173
02:19:54,497 --> 02:19:56,533
TODAY A LOT ABOUT POLYMERS AND 

3174
02:19:56,533 --> 02:19:59,502
DELIVERY STRATEGIES BUT ANOTHER 

3175
02:19:59,502 --> 02:20:02,839
STEP IS WHAT ARE WE DOING WITH 

3176
02:20:02,839 --> 02:20:04,641
THE HOST NICHE, WITH THE HOST 

3177
02:20:04,641 --> 02:20:07,344
TISSUE, IN ORDER TO MAKE IT MORE

3178
02:20:07,344 --> 02:20:09,713
PERMISSIBLE FOR DONOR CELLS TO 

3179
02:20:09,713 --> 02:20:11,414
INTEGRATE AND REALLY DO WHAT WE 

3180
02:20:11,414 --> 02:20:14,784
WANT THEM TO DO?  BECAUSE 

3181
02:20:14,784 --> 02:20:18,254
SURVIVAL IS OBVIOUSLY NOT THE 

3182
02:20:18,254 --> 02:20:19,623
PRIMARY INVOLVED AND YOU SEE 

3183
02:20:19,623 --> 02:20:22,058
THOSE NEURONS THAT SURVIVE THEY 

3184
02:20:22,058 --> 02:20:24,995
DON'T NECESSARILY THE ONES THAT 

3185
02:20:24,995 --> 02:20:26,396
WITHDRAW NEW RIGHTS OR THE ONES 

3186
02:20:26,396 --> 02:20:28,531
THAT WOULD FORM A LOT OF 

3187
02:20:28,531 --> 02:20:31,768
SYNAPSES SO THAT IS WHERE WE 

3188
02:20:31,768 --> 02:20:33,837
HAVE TO PRIORITIZE FUNCTION AS A

3189
02:20:33,837 --> 02:20:35,839
RESULT FOR TRANSPLANTATION AND 

3190
02:20:35,839 --> 02:20:41,077
ALSO MODIFYING THE ENVIRONMENT. 

3191
02:20:41,077 --> 02:20:45,915
THANK YOU.

3192
02:20:45,915 --> 02:20:50,186
>> KIMBERLEY IS NEXT.  AND
ON 

3193
02:20:50,186 --> 02:21:00,597
DECK IS DEMETRI SHANE.

3194
02:21:03,533 --> 02:21:09,372
>> MY NAME IS KIM AND I'M
A 

3195
02:21:09,372 --> 02:21:10,507
NEUROOPHTHALMO

3196
02:21:10,507 --> 02:21:11,174
NEUROOPHTHALMOLOGIST.  THE NICE 

3197
02:21:11,174 --> 02:21:11,841
THING ABOUT GOING AFTER PETER IS

3198
02:21:11,841 --> 02:21:15,178
WE TRY TO REGENERATE THE OPTIC 

3199
02:21:15,178 --> 02:21:16,813
NERVE THAT WORKS WITH THE EYE TO

3200
02:21:16,813 --> 02:21:20,884
THE BRAIN.  MAY I HAVE MY SLIDE?

3201
02:21:20,884 --> 02:21:22,886
OH, PERFECT.  SO THIS IS A 

3202
02:21:22,886 --> 02:21:23,753
DIFFICULT QUESTION OR CHALLENGE 

3203
02:21:23,753 --> 02:21:26,056
FOR A NUMBER OF REASONS AND SO 

3204
02:21:26,056 --> 02:21:27,524
ONE IF I WOULD SAY THE WINS THAT

3205
02:21:27,524 --> 02:21:30,460
WE HAVE IN THIS FIELD IS THAT WE

3206
02:21:30,460 --> 02:21:32,629
DO HAVE A SOURCE OF RETINAL 

3207
02:21:32,629 --> 02:21:36,032
GANGLION CELLS.  THEY DON'T 

3208
02:21:36,032 --> 02:21:37,534
NECESSARILY FUNCTION PERFECTLY 

3209
02:21:37,534 --> 02:21:39,402
BUT THE BIG CHALLENGE IS 

3210
02:21:39,402 --> 02:21:40,704
INTEGRATION AND IT HAS TO OCCUR 

3211
02:21:40,704 --> 02:21:43,306
AT TWO LEVELS.  RIGHT?  AND SO 

3212
02:21:43,306 --> 02:21:45,475
CAN YOU CLICK NEXT, PLEASE?  AND

3213
02:21:45,475 --> 02:21:49,045
SO ONE, WE'RE TRYING TO 

3214
02:21:49,045 --> 02:21:49,746
TRANSBREAST IMPLANT A NEURON 

3215
02:21:49,746 --> 02:21:52,482
INTO A TISSUE THAT'S HIGHLY 

3216
02:21:52,482 --> 02:21:53,917
STRUCTURED AND LAYERED. 

3217
02:21:53,917 --> 02:21:56,086
WE NEED TO HAVE THE NEURON IN 

3218
02:21:56,086 --> 02:21:58,054
THE CORRECT ORIENTATION AND THEN

3219
02:21:58,054 --> 02:21:59,923
ONCE IT ACTUALLY FINDS ITSELF IN

3220
02:21:59,923 --> 02:22:00,857
THE RIGHT PLACE IT'S GOT TO 

3221
02:22:00,857 --> 02:22:01,958
CONNECT WITH THE NEIGHBORING 

3222
02:22:01,958 --> 02:22:03,293
CELLS IN THE RETINA AND THEN 

3223
02:22:03,293 --> 02:22:05,628
IT'S GOT TO GROW AN AX ON INTO 

3224
02:22:05,628 --> 02:22:07,497
THE BRAIN AND THEN RECONNECT 

3225
02:22:07,497 --> 02:22:08,231
WITH THE BRAIN. 

3226
02:22:08,231 --> 02:22:10,266
AND SO WHAT WE'RE SEEING IS THIS

3227
02:22:10,266 --> 02:22:12,102
IS A DEVELOPMENTAL PROCESS 

3228
02:22:12,102 --> 02:22:13,703
UNLIKE A SITUATION WHERE YOU CAN

3229
02:22:13,703 --> 02:22:15,739
HAVE A MATURE CELL THAT YOU 

3230
02:22:15,739 --> 02:22:16,773
IMPLANT INTO YOUR TISSUE YOU'VE 

3231
02:22:16,773 --> 02:22:19,409
GOT TO IMPLANT A CELL THAT HAS 

3232
02:22:19,409 --> 02:22:20,744
TO DO MULTIPLE FUNCTIONS AND 

3233
02:22:20,744 --> 02:22:22,412
CONTINUE TO DEVELOP TO 

3234
02:22:22,412 --> 02:22:24,814
INTEGRATE.  AND SO I KIND OF 

3235
02:22:24,814 --> 02:22:28,685
EQUATE THIS AS TOO BAD WE TRIED 

3236
02:22:28,685 --> 02:22:29,919
BUT YOU CAN'T TAKE A CHIP AND 

3237
02:22:29,919 --> 02:22:32,689
THROW IT ONTO A MOTHERBOARD AND 

3238
02:22:32,689 --> 02:22:34,891
SAY I HOPE IT WORKS AND CONNECTS

3239
02:22:34,891 --> 02:22:36,259
AND THAT'S WHAT MAKES THIS 

3240
02:22:36,259 --> 02:22:36,893
CHALLENGE REALLY DIFFICULT AND 

3241
02:22:36,893 --> 02:22:38,795
THE STRATEGIES THAT PEOPLE IN 

3242
02:22:38,795 --> 02:22:40,130
OUR FIELD TEND TO USE TO 

3243
02:22:40,130 --> 02:22:43,133
OVERCOME THIS CHALLENGE IS TO 

3244
02:22:43,133 --> 02:22:45,068
REACTIVATE SIGNALLING PATHWAYS 

3245
02:22:45,068 --> 02:22:47,170
IN DEVELOPMENT THAT DROVE AXON 

3246
02:22:47,170 --> 02:22:48,805
GROWTH BUT THE PROBLEM IS THAT 

3247
02:22:48,805 --> 02:22:50,440
THESE PATHWAYS WERE TURNED OFF 

3248
02:22:50,440 --> 02:22:52,642
FOR A REASON.  IF YOU TURN ON 

3249
02:22:52,642 --> 02:22:54,911
THESE PATHWAYS LIKE ENTOR AND 

3250
02:22:54,911 --> 02:22:56,446
NOT REGULATE THEM YOU'RE GOING 

3251
02:22:56,446 --> 02:22:58,381
TO CAUSE OTHER PROBLEMS LIKE 

3252
02:22:58,381 --> 02:23:03,086
CANCER AND WHATNOT SO WHATEVER 

3253
02:23:03,086 --> 02:23:03,920
STRATEGY WE DO WITH THIS IS WE 

3254
02:23:03,920 --> 02:23:05,388
HAVE TO BE ABLE TO CONTROL.  WE 

3255
02:23:05,388 --> 02:23:07,690
HAVE TO TURN THINGS ON AND ALSO 

3256
02:23:07,690 --> 02:23:09,592
TURN THINGS OFF WHEN WE NEED 

3257
02:23:09,592 --> 02:23:11,127
THEM AND ARZ AS FAR AS TO SEE DO

3258
02:23:11,127 --> 02:23:12,962
WE NEED A KILL SWITCH. 

3259
02:23:12,962 --> 02:23:15,732
DO WE NEED SOME TYPE OF DRUG 

3260
02:23:15,732 --> 02:23:17,400
INDUCED GENE EXPRESSION AND 

3261
02:23:17,400 --> 02:23:19,869
ANOTHER THAT WILL TURN OFF THESE

3262
02:23:19,869 --> 02:23:21,070
CELLS IF THEY START TO DO 

3263
02:23:21,070 --> 02:23:22,405
SOMETHING AVENUE RANT THAT WE 

3264
02:23:22,405 --> 02:23:25,542
DON'T WANT?  CAN YOU CLICK NEXT,

3265
02:23:25,542 --> 02:23:29,779
PLEASE?  OKAY, NEXT AGAIN.  NEXT

3266
02:23:29,779 --> 02:23:35,485
AGAIN.  AND THE OTHER THING THAT

3267
02:23:35,485 --> 02:23:37,587
WE DON'T TALK ABOUT IS THERE ARE

3268
02:23:37,587 --> 02:23:39,289
OVER 30 DIFFERENT SUBTYPES OF 

3269
02:23:39,289 --> 02:23:42,025
RETINAL GANGLION CELLS IN THE 

3270
02:23:42,025 --> 02:23:43,693
EYE.  THEY PORP DIFFERENT THINGS

3271
02:23:43,693 --> 02:23:45,061
AND WE'RE VISUAL ANIMALS VISUAL 

3272
02:23:45,061 --> 02:23:47,864
IS A COMPLEX PROCESS AND THESE 

3273
02:23:47,864 --> 02:23:49,065
AXONS TARGET DIFFERENT PARTS OF 

3274
02:23:49,065 --> 02:23:51,000
THE BRAIN.  IF YOU'RE TRYING TO 

3275
02:23:51,000 --> 02:23:52,669
ACTUALLY PUT REPLACEMENT 

3276
02:23:52,669 --> 02:23:54,103
BEGANING LEON CELLS ARE YOU 

3277
02:23:54,103 --> 02:23:55,004
GOING TO GET THE RIGHT ONES TO 

3278
02:23:55,004 --> 02:23:57,106
GO INTO THE RIGHT PLACE?  NEXT 

3279
02:23:57,106 --> 02:23:58,308
SLIDE, PLEASE. 

3280
02:23:58,308 --> 02:23:59,876
AND ONE OF THE BIG CHALLENGES WE

3281
02:23:59,876 --> 02:24:01,878
NEED TO ADDRESS IS WHAT MODEL 

3282
02:24:01,878 --> 02:24:03,246
SYSTEM ARE WE GOING TO USE?  

3283
02:24:03,246 --> 02:24:04,681
THERE ARE A LOT OF DIFFERENT 

3284
02:24:04,681 --> 02:24:06,549
OPTIC NERVE DISEASES BUT THEY 

3285
02:24:06,549 --> 02:24:08,418
CAUSE DISEASES AT DIFFERENT 

3286
02:24:08,418 --> 02:24:10,520
RATES DO WE WANT TO DO A 

3287
02:24:10,520 --> 02:24:11,921
STROKE-LIKE OPTIC DISEASE WHERE 

3288
02:24:11,921 --> 02:24:15,358
YOU GET SIMULTANEOUS DAMAGE TO 

3289
02:24:15,358 --> 02:24:16,693
NEURONS ALL AT ONCE SO THEY'RE 

3290
02:24:16,693 --> 02:24:19,229
ALL SYNCHRONIZED, PROBABLY DIE 

3291
02:24:19,229 --> 02:24:21,631
AT A SYNCHRONOUS RATE OR DO 

3292
02:24:21,631 --> 02:24:23,066
SOMETHING LIKE GLAUCOMA WHICH IS

3293
02:24:23,066 --> 02:24:24,567
A SLOW COMPRESSIVE DISEASE WHERE

3294
02:24:24,567 --> 02:24:26,836
YOU HAVE A COUPLE HUNDRED OR 

3295
02:24:26,836 --> 02:24:27,770
THOUSAND CELLS THAT ARE DYING AT

3296
02:24:27,770 --> 02:24:29,906
A TIME BUT THEY'RE ALL DYING AT 

3297
02:24:29,906 --> 02:24:30,807
DIFFERENT RATES AND HOW ARE YOU 

3298
02:24:30,807 --> 02:24:32,909
GOING TO GET THEM TO FILL IN TO 

3299
02:24:32,909 --> 02:24:34,677
THE PARTICULAR SPOTS THAT ARE 

3300
02:24:34,677 --> 02:24:35,545
NEEDED?  SO THIS IS A BIG 

3301
02:24:35,545 --> 02:24:38,915
CHALLENGE FOR US IN THE FIELD.  

3302
02:24:38,915 --> 02:24:44,554
NEXT SLIDE, PLEASE.  THIS IS A 

3303
02:24:44,554 --> 02:24:45,955
DEVELOPING PROCESS AND CELL 

3304
02:24:45,955 --> 02:24:49,058
SURVIVAL ACTS ON GROWTH, SYNAPSE

3305
02:24:49,058 --> 02:24:50,526
FORMATION, MYELINATION, THESE 

3306
02:24:50,526 --> 02:24:52,562
ARE ALL INDEPENDENTLY REGULATED 

3307
02:24:52,562 --> 02:24:57,500
PROCESSES AND THEY OCCUR 

3308
02:24:57,500 --> 02:25:00,536
SEQUEN

3309
02:25:00,536 --> 02:25:01,104
SEQUENTIALLY.  AND I THINK 

3310
02:25:01,104 --> 02:25:02,472
THAT'S A REALLY BIG PROBLEM.  

3311
02:25:02,472 --> 02:25:04,240
YOU KNOW, LIKE, SO OUR LAB WORKS

3312
02:25:04,240 --> 02:25:07,110
ON ELECTRIC FIELDS AND USING 

3313
02:25:07,110 --> 02:25:08,978
THAT TO GUIDE AXON GROWTH BUT WE

3314
02:25:08,978 --> 02:25:12,582
DON'T HAVE THE EXPERTISE IN 

3315
02:25:12,582 --> 02:25:18,421
THINGS LIKE FLUOROAL SURVIVAL SO

3316
02:25:18,421 --> 02:25:19,522
WE NEED TO CROSS TRAIN OR WORK 

3317
02:25:19,522 --> 02:25:19,789
TOGETHER. 

3318
02:25:19,789 --> 02:25:23,526
I TRIED TO WORK WITH PEOPLE LIKE

3319
02:25:23,526 --> 02:25:25,361
A DOCTOR IN L.A. AND I'M IN 

3320
02:25:25,361 --> 02:25:28,431
BOSTON DO I SHIP MY RATS OVER 

3321
02:25:28,431 --> 02:25:29,799
AND YOU INJECT SOME CELLS AND 

3322
02:25:29,799 --> 02:25:31,200
SHIP THE RATS BACK AND THEN 

3323
02:25:31,200 --> 02:25:33,303
WE'RE GOING TO STIMULATE THEM?  

3324
02:25:33,303 --> 02:25:35,872
HOW ARE WE GOING TO ACTUALLY DO 

3325
02:25:35,872 --> 02:25:36,973
THAT?  AND SO I FEEL LIKE WE 

3326
02:25:36,973 --> 02:25:39,642
HAVE SOME SILOED EXPERTISE.  I 

3327
02:25:39,642 --> 02:25:41,277
ALSO, YOU KNOW, I WAS TRAINED AS

3328
02:25:41,277 --> 02:25:44,213
A MOLECULAR BIOLOGIST BUT I ALSO

3329
02:25:44,213 --> 02:25:47,450
THINK IN GENERAL THERE'S A BIG 

3330
02:25:47,450 --> 02:25:48,851
BIAS AGAINST NON MOLECULAR 

3331
02:25:48,851 --> 02:25:49,919
TECHNOLOGIES AND I FEEL THIS 

3332
02:25:49,919 --> 02:25:55,591
WHEN I APPLY  FOR GRANTS AND WE 

3333
02:25:55,591 --> 02:25:57,093
NEED TO THINK OUTSIDE THE BOX 

3334
02:25:57,093 --> 02:25:58,928
ASKING THE BIG QUESTIONS AND 

3335
02:25:58,928 --> 02:26:03,933
COLLABORATING WITH PEOPLE IN 

3336
02:26:03,933 --> 02:26:05,068
ENGINEERING AND WHATNOT. 

3337
02:26:05,068 --> 02:26:07,437
IN ORDER TO HAVE SYNERGISTIC 

3338
02:26:07,437 --> 02:26:08,604
APPROACHES.  STEM CELLS ARE 

3339
02:26:08,604 --> 02:26:09,472
DEFINED BY THEIR ENVIRONMENT AND

3340
02:26:09,472 --> 02:26:13,242
WE DO ALL OF THESE THINGS TO 

3341
02:26:13,242 --> 02:26:18,781
MODULATE THE CELL BUT WHAT ABOUT

3342
02:26:18,781 --> 02:26:21,050
THE EXTRINSIC BARRIERS.  WE NEED

3343
02:26:21,050 --> 02:26:22,552
TO INVOLVE THE CLINICIAN AND I 

3344
02:26:22,552 --> 02:26:23,953
KNOW THIS IS SELF-SERVING THE 

3345
02:26:23,953 --> 02:26:25,221
CLINICIAN IS GOING TO HELP 

3346
02:26:25,221 --> 02:26:27,056
INFORM US AS TO WHAT IS ACTUALLY

3347
02:26:27,056 --> 02:26:28,224
POSSIBLE.  I CAN'T TELL YOU THE 

3348
02:26:28,224 --> 02:26:29,625
NUMBER OF TIMES MY EVENING 

3349
02:26:29,625 --> 02:26:35,698
NEARING CL -- ENGINEERING 

3350
02:26:35,698 --> 02:26:37,066
COLLABORATORS HAVE TOLD US TO DO

3351
02:26:37,066 --> 02:26:39,669
THIS.  THEY'RE GOING TO TELL YOU

3352
02:26:39,669 --> 02:26:40,803
WHAT POSSIBLE AND MOST 

3353
02:26:40,803 --> 02:26:43,539
IMPORTANTLY WILL TELL YOU WHAT 

3354
02:26:43,539 --> 02:26:45,708
IS A RELEVANT OUTCOME?  HOW ARE 

3355
02:26:45,708 --> 02:26:48,578
WE GOING TO MEASURE THIS?  I USE

3356
02:26:48,578 --> 02:26:49,579
RATS.  THEY AREN'T EVEN VISUAL 

3357
02:26:49,579 --> 02:26:51,647
ANIMAL TO THE TOPICS THAT WERE 

3358
02:26:51,647 --> 02:26:52,749
DISCUSSED EARLIER I HAVE -- 

3359
02:26:52,749 --> 02:26:54,984
BEHAVIORAL ASSAYS WHEN USING AN 

3360
02:26:54,984 --> 02:26:57,453
ANIMAL THAT DOESN'T USE ITS EYES

3361
02:26:57,453 --> 02:27:00,189
TO SURVIVE IN THE ENVIRONMENT I 

3362
02:27:00,189 --> 02:27:01,024
THINK INVOLVING THE CLINICIAN AT

3363
02:27:01,024 --> 02:27:02,825
THE EARLY STAGE TO SEE AND ASK 

3364
02:27:02,825 --> 02:27:03,926
WHAT IS ACTUALLY IMPORTANT WHAT 

3365
02:27:03,926 --> 02:27:05,928
ARE WE AIMING TO ACHIEVE IS 

3366
02:27:05,928 --> 02:27:08,965
REALLY IMPORTANT?  THANK YOU SO 

3367
02:27:08,965 --> 02:27:19,075
MUC

3368
02:27:21,144 --> 02:27:21,277
MUCH.

3369
02:27:21,277 --> 02:27:26,649
>>  THANK YOU FOR INVITING
ME 

3370
02:27:26,649 --> 02:27:32,622
AND FEW OTHER INVESTIGATORS TO 

3371
02:27:32,622 --> 02:27:34,457
SHARE.  I THINK I WAS MORE 

3372
02:27:34,457 --> 02:27:35,558
RELIGIOUS AT ADHERING TO THE 

3373
02:27:35,558 --> 02:27:39,462
POLICEMEN AT A TIME.  -- 

3374
02:27:39,462 --> 02:27:39,729
TEMPLATE. 

3375
02:27:39,729 --> 02:27:40,630
NEXT SLIDE, PLEASE. 

3376
02:27:40,630 --> 02:27:44,267
I CAME HERE TO ADVOCATE FOR IPS 

3377
02:27:44,267 --> 02:27:46,502
DERIVED THERAPIES.  SEEMS I'M 

3378
02:27:46,502 --> 02:27:51,941
PREACHING TO THE CHOIR.  WE HAVE

3379
02:27:51,941 --> 02:27:57,413
SOME PROTOCOLS THAT WE WORK ON 

3380
02:27:57,413 --> 02:27:59,849
IN THE LAB AND PUSH THE CELLS IN

3381
02:27:59,849 --> 02:28:04,554
DIFFERENT DIRECTIONS AND MOSTLY 

3382
02:28:04,554 --> 02:28:06,289
FOCUSED ON THE CELLS AND WE WORK

3383
02:28:06,289 --> 02:28:08,024
WITH DIFFERENT CELLS NOW AND 

3384
02:28:08,024 --> 02:28:11,360
ITEN KNOW SITES, MACROPHAGES AND

3385
02:28:11,360 --> 02:28:14,430
KNOW SIS CEPTORS FOR DISEASE 

3386
02:28:14,430 --> 02:28:17,233
MODEL PURPOSES.  NEXT.  SO WHAT 

3387
02:28:17,233 --> 02:28:18,601
I THOUGHT ARE THAT THE 

3388
02:28:18,601 --> 02:28:20,203
OPPORTUNITY THAT WE HAVE NOW. 

3389
02:28:20,203 --> 02:28:24,140
WITH THESE THERAPIES?  SO FIRST 

3390
02:28:24,140 --> 02:28:27,944
OF ALL, IPSCS ARE AMAZING AND 

3391
02:28:27,944 --> 02:28:32,215
CAN DO A LOT OF THINGS HAVE 

3392
02:28:32,215 --> 02:28:34,016
UNLIMITED CELL SOURCE FOR CELL 

3393
02:28:34,016 --> 02:28:36,586
THERAPIES BUT ALSO -- WE CAN 

3394
02:28:36,586 --> 02:28:39,789
ALSO SHARE SOME IPS LINES AND WE

3395
02:28:39,789 --> 02:28:43,192
DON'T REALLY HAVE TO WORK 

3396
02:28:43,192 --> 02:28:44,760
THROUGH 23 LINES THAT DON'T WORK

3397
02:28:44,760 --> 02:28:48,998
TO FIND ONE THAT DOES WORK.  AND

3398
02:28:48,998 --> 02:28:51,367
ANOTHER THING I THOUGHT IS 

3399
02:28:51,367 --> 02:28:53,402
IMPORTANT TO MENTION IS THIS -- 

3400
02:28:53,402 --> 02:28:56,672
ALL THE SINGLE CELL TECHNOLOGIES

3401
02:28:56,672 --> 02:29:01,844
THAT WE HAVE IN WHAT'S COMING 

3402
02:29:01,844 --> 02:29:03,779
UP.  REALLY GIVES US THE 

3403
02:29:03,779 --> 02:29:05,414
OPPORTUNITY TO KNOW THE 

3404
02:29:05,414 --> 02:29:06,415
LANDSCAPE OF THE TISSUE, TISSUE 

3405
02:29:06,415 --> 02:29:10,319
IS COMPLEX, IT'S NOT ONE CELL 

3406
02:29:10,319 --> 02:29:13,256
TYPE EVEN WITHIN ONE CELL TIME 

3407
02:29:13,256 --> 02:29:18,528
THERE'S ANDROTIME 

3408
02:29:18,528 --> 02:29:21,831
THERE'S ANDRO AND WE DID THAT --

3409
02:29:21,831 --> 02:29:25,001
WE YAUDZ IPSCS. 

3410
02:29:25,001 --> 02:29:26,936
AND SINGLE CELL TRAN SCRIP 

3411
02:29:26,936 --> 02:29:28,004
TOPICS TO LEARN ABOUT THE 

3412
02:29:28,004 --> 02:29:29,505
PROCESS OF DIFFERENTIATION. 

3413
02:29:29,505 --> 02:29:31,841
AND IMPROVE THAT PROCESS DOWN 

3414
02:29:31,841 --> 02:29:35,211
THE LINE.  NEXT.  SO IN TERMS OF

3415
02:29:35,211 --> 02:29:39,615
CHALLENGES, I LISTED FOUR.  WE 

3416
02:29:39,615 --> 02:29:41,551
TALKED ABOUT REPRODUCIBILITY OF 

3417
02:29:41,551 --> 02:29:43,085
THE DIFFERENTIATION PROTOCOLS.  

3418
02:29:43,085 --> 02:29:44,320
I THINK THAT'S THE MAIN 

3419
02:29:44,320 --> 02:29:47,256
CHALLENGE IN IPS WORK BECAUSE 

3420
02:29:47,256 --> 02:29:55,565
EVERY LINE IS DIFFERENT.  WE 

3421
02:29:55,565 --> 02:29:56,699
MENTIONED ANIMAL MODELS AND THE 

3422
02:29:56,699 --> 02:29:59,936
THING IS SPECIFICALLY, RELEVANT 

3423
02:29:59,936 --> 02:30:03,940
FOR THE CONDITIONED SO WE'RE 

3424
02:30:03,940 --> 02:30:08,544
GOOD AT INJURING ANIMALS BUT CAN

3425
02:30:08,544 --> 02:30:13,049
WE REGENERATE THE HUMAN 

3426
02:30:13,049 --> 02:30:15,117
CONDITION AND CELL THERAPIES 

3427
02:30:15,117 --> 02:30:18,621
USUALLY REQUIRE A CARRIER SO 

3428
02:30:18,621 --> 02:30:21,057
THAT COMPLICATES THINGS AND WE 

3429
02:30:21,057 --> 02:30:22,792
NEED TO DESIGN NOT ONLY THE CELL

3430
02:30:22,792 --> 02:30:23,659
BUT THE CARRIER AND ANOTHER 

3431
02:30:23,659 --> 02:30:25,795
CHALLENGE I THINK THAT WE DID 

3432
02:30:25,795 --> 02:30:27,463
MENTION HERE IS CELL TRACKING 

3433
02:30:27,463 --> 02:30:30,433
HOW DO WE ENSURE WHERE THESE 

3434
02:30:30,433 --> 02:30:32,568
CELLS END UP, WHAT'S THE FATE IN

3435
02:30:32,568 --> 02:30:35,838
THE END IN THE ANIMAL.  IT'S -- 

3436
02:30:35,838 --> 02:30:38,074
ALL THE STUDIES ARE DESIGNED FOR

3437
02:30:38,074 --> 02:30:41,644
DRUGS, NOT FOR CELL THERAPIES.  

3438
02:30:41,644 --> 02:30:44,513
NEXT.  AND HOW I THOUGHT THAT WE

3439
02:30:44,513 --> 02:30:47,917
CAN ADDRESS THESE CHALLENGES SO 

3440
02:30:47,917 --> 02:30:50,219
STANDARDIZING PROTOCOLS I THINK 

3441
02:30:50,219 --> 02:30:52,655
PROGRAMS LIKE THAT HAVE A LOT OF

3442
02:30:52,655 --> 02:30:56,959
POWER TO FORCE INVESTIGATORS TO 

3443
02:30:56,959 --> 02:31:02,064
STANDARDIZE AND SHARE RESOURCES 

3444
02:31:02,064 --> 02:31:05,534
AND PROTOCOLS.  RECENTLY WE HAVE

3445
02:31:05,534 --> 02:31:08,537
A PAPER IN SPECIAL MEDICINE 

3446
02:31:08,537 --> 02:31:14,543
WHERE WE USED ANIMAL MODEL AND 

3447
02:31:14,543 --> 02:31:18,147
ORGAN ON CHIP SYSTEM SO YOU CAN 

3448
02:31:18,147 --> 02:31:21,751
USE THE INVIVO ANIMAL MODEL BUT 

3449
02:31:21,751 --> 02:31:24,220
ALSO COMBINE IT WITH ORGAN AND 

3450
02:31:24,220 --> 02:31:25,388
CHIP SYSTEMS THAT HAVE THE 

3451
02:31:25,388 --> 02:31:27,957
ADVANTAGE OF USING THE ACTUAL 

3452
02:31:27,957 --> 02:31:33,696
HUMAN CELLS.  NEXT.  AND WE ALSO

3453
02:31:33,696 --> 02:31:35,898
DEVELOPING SOME OFF THE SHELF 

3454
02:31:35,898 --> 02:31:39,602
CELL DELIVERY SYSTEMS.   

3455
02:31:39,602 --> 02:31:43,806
SCAFFOLDS ARE A BIG FIELD.  THIS

3456
02:31:43,806 --> 02:31:49,345
IS OUR HEAL INITIATIVE STUDY IN 

3457
02:31:49,345 --> 02:31:53,082
DEVELOPING THE MICRO INJECTION. 

3458
02:31:53,082 --> 02:31:56,919
NEXT AND NEXT.  NEXT.  AND LAST 

3459
02:31:56,919 --> 02:31:58,854
POINT I WANT TO MAKE IS I THINK 

3460
02:31:58,854 --> 02:32:02,958
THERE IS A LOT OF OPPORTUNITY TO

3461
02:32:02,958 --> 02:32:03,859
DEVELOP IMAGING AND CELL 

3462
02:32:03,859 --> 02:32:07,263
TRACKING TECHNIQUES.  HERE WE 

3463
02:32:07,263 --> 02:32:08,597
PUBLISHED A MULTIPLE LABEL 

3464
02:32:08,597 --> 02:32:11,734
EXISTING FOR CELLS IN THE LARGE 

3465
02:32:11,734 --> 02:32:15,037
ANIMAL MODEL TO TRACK IN THE 

3466
02:32:15,037 --> 02:32:16,405
KNEE IN THE PIG BUT I THINK 

3467
02:32:16,405 --> 02:32:18,140
THERE'S A LOT OF THINGS WE CAN 

3468
02:32:18,140 --> 02:32:22,745
DO BETTER IN TERMS OF TRACKING 

3469
02:32:22,745 --> 02:32:30,820
CELLS AND DEVELOPING THESE 

3470
02:32:30,820 --> 02:32:35,558
TECHNOLOGIES.  THANK YOU.

3471
02:32:35,558 --> 02:32:41,430
>> DAN FOLLOWED BY TONY.

3472
02:32:41,430 --> 02:32:44,233
>> THANK YOU VERY MUCH.  I
HOPE 

3473
02:32:44,233 --> 02:32:47,069
THAT THE CLICKER DOES WORK.  MY 

3474
02:32:47,069 --> 02:32:52,541
NAME IS DAN.  I'M AN ORTHOPEDIC 

3475
02:32:52,541 --> 02:32:57,913
SURGEON.  I HAD MY FIRST PART OF

3476
02:32:57,913 --> 02:33:02,985
MY CLINIC IN EUROPE AND NOW 

3477
02:33:02,985 --> 02:33:05,221
HERE.  THESE ARE MY DISCLOE 

3478
02:33:05,221 --> 02:33:06,889
SURES.  WHEN YOU TALK TO 

3479
02:33:06,889 --> 02:33:08,057
SURGEONS ABOUT STEM CELL 

3480
02:33:08,057 --> 02:33:09,358
THERAPIES THERE'S A LOT OF 

3481
02:33:09,358 --> 02:33:10,659
CONFUSION ABOUT WHAT IS ALLOWED,

3482
02:33:10,659 --> 02:33:12,661
WHAT IS NOT ALLOWED, WHAT IS 

3483
02:33:12,661 --> 02:33:14,230
REGULATED, HOW IT'S REGULATED.  

3484
02:33:14,230 --> 02:33:15,364
WHAT IS AVAILABLE AND WHAT IS 

3485
02:33:15,364 --> 02:33:16,599
STILL IN STUDIES AND I THINK 

3486
02:33:16,599 --> 02:33:19,535
THAT'S ONE OF THE THINGS WHERE 

3487
02:33:19,535 --> 02:33:21,737
NIH AND FDA AND ACADEMIC 

3488
02:33:21,737 --> 02:33:23,739
SOCIETIES HAVE A BIG ROLE IN 

3489
02:33:23,739 --> 02:33:24,740
EDUCATING WHAT IS ABOVE BOARD 

3490
02:33:24,740 --> 02:33:31,180
AND WHAT'S NOT AND HIGH HOW TO 

3491
02:33:31,180 --> 02:33:33,549
TAKE THE FIELD TO MORE LIGHTS.  

3492
02:33:33,549 --> 02:33:35,184
THERE ARE A FEW NOT SO GOOD 

3493
02:33:35,184 --> 02:33:35,951
TECHNOLOGIES THAT ARE OUT THERE 

3494
02:33:35,951 --> 02:33:38,087
WITHOUT BEING REGULAR LATESED 

3495
02:33:38,087 --> 02:33:39,522
PROPERLY SO IT'S REALLY 

3496
02:33:39,522 --> 02:33:41,056
IMPORTANT TO COME UP WITH 

3497
02:33:41,056 --> 02:33:41,957
SOLUTIONS THAT HELP THE FIELD AS

3498
02:33:41,957 --> 02:33:43,292
A CLINICIAN FURTHER. 

3499
02:33:43,292 --> 02:33:44,693
AND THAT'S DIFFICULT.  YOU HAVE 

3500
02:33:44,693 --> 02:33:45,728
TO MAKE SURE THAT IT DOESN'T 

3501
02:33:45,728 --> 02:33:47,963
BECOME SO DIFFICULT THAT YOU END

3502
02:33:47,963 --> 02:33:49,799
UP HAVING ALL YOUR CLINICIANS 

3503
02:33:49,799 --> 02:33:51,734
FRUSTRATED BY THE CHALLENGES 

3504
02:33:51,734 --> 02:33:53,903
THAT WE HAVE.  AND THEREFORE, 

3505
02:33:53,903 --> 02:33:56,172
SORT OF LEADING THE 

3506
02:33:56,172 --> 02:33:57,239
TRANSLATIONAL FIELD BUT YOU ALSO

3507
02:33:57,239 --> 02:34:00,643
HAVE TO MAKE SURE YOU DON'T 

3508
02:34:00,643 --> 02:34:02,011
OVERPROMISE WHAT YOU CAN BRING 

3509
02:34:02,011 --> 02:34:03,846
TO THE CLINICAL FIELD BECAUSE OF

3510
02:34:03,846 --> 02:34:05,514
THE BASIC SCIENCE AND ALL THE 

3511
02:34:05,514 --> 02:34:06,782
OPPORTUNITY THAT WORKS IN THE 

3512
02:34:06,782 --> 02:34:08,350
LAB AND I KNOW THIS IS SOMETHING

3513
02:34:08,350 --> 02:34:10,019
THAT YOU GUYS ARE ALL FAMILIAR 

3514
02:34:10,019 --> 02:34:12,555
WITH BUT NOT ALL OF MY CLINICAL 

3515
02:34:12,555 --> 02:34:13,856
COLLEAGUES SHARE THAT SAME 

3516
02:34:13,856 --> 02:34:15,424
PERCEPTION AND NOT ALL OF OUR 

3517
02:34:15,424 --> 02:34:18,594
BASIC SCIENTISTS UNDERSTAND.  

3518
02:34:18,594 --> 02:34:19,228
AND THAT'S SOMETHING WHERE SOME 

3519
02:34:19,228 --> 02:34:21,063
OF US CLINICIANS HAVE BEEN 

3520
02:34:21,063 --> 02:34:22,531
FORTUNATE TO BE ABLE TO BE PART 

3521
02:34:22,531 --> 02:34:25,534
OF THESE.  I AM JUST WANTING TO 

3522
02:34:25,534 --> 02:34:27,736
SHARE PART OF THE STORY THAT'S 

3523
02:34:27,736 --> 02:34:29,438
THERE AND COME BACK TO THE 

3524
02:34:29,438 --> 02:34:32,708
PREVIOUS SLIDE, I'M SORRY.  SO 

3525
02:34:32,708 --> 02:34:35,911
THE RECLAIM TECHNOLOGY IS 

3526
02:34:35,911 --> 02:34:37,046
SOMETHING WE CAME UP WITH 

3527
02:34:37,046 --> 02:34:39,882
BECAUSE WE DID THESE TRIALS IN 

3528
02:34:39,882 --> 02:34:41,584
EUROPE UNDER THE EMA GUIDANCE 

3529
02:34:41,584 --> 02:34:43,953
AND THE MACY PRODUCT WHICH IS 

3530
02:34:43,953 --> 02:34:46,822
THE CELL THERAPY UNDER FDA 

3531
02:34:46,822 --> 02:34:49,091
GUIDANCE AND THOSE WERE DONE IN 

3532
02:34:49,091 --> 02:34:51,160
LARGER TRIALS BECAUSE IT'S 

3533
02:34:51,160 --> 02:34:52,495
DIFFICULT TO DO IN ONE CENTER.  

3534
02:34:52,495 --> 02:34:56,131
IT ALSO TAUGHT ME THAT DOING TWO

3535
02:34:56,131 --> 02:34:57,333
SURGERIES TO FILL A POTHOLE IS 

3536
02:34:57,333 --> 02:34:58,734
PROBABLY NOT THE WAY FORWARD.  

3537
02:34:58,734 --> 02:35:00,669
WE WANT TO DO THIS IN 

3538
02:35:00,669 --> 02:35:02,338
INJECTABLE.  WE WANT TO BE ABLE 

3539
02:35:02,338 --> 02:35:04,573
TO DO THIS IN ONE TECHNIQUE AND 

3540
02:35:04,573 --> 02:35:07,376
CARTILAGE IS A RELATIVELY SIMPLE

3541
02:35:07,376 --> 02:35:08,410
TISSUE.  THE CELLS STILL KNOW 

3542
02:35:08,410 --> 02:35:10,746
WHAT IT'S LIKE TO MAKE CARTILAGE

3543
02:35:10,746 --> 02:35:12,381
BUT THE TISSUE FUNCTIONALLY 

3544
02:35:12,381 --> 02:35:13,849
DOESN'T DO SO ANYMORE WHEN IT'S 

3545
02:35:13,849 --> 02:35:16,385
DAMAGED SO THE HYPOTHESIS WAS AS

3546
02:35:16,385 --> 02:35:18,020
YOU CLEAN THE DEFECT TO MAKE 

3547
02:35:18,020 --> 02:35:21,323
SURE IT'S NICE AND STABLE CAN'T 

3548
02:35:21,323 --> 02:35:22,725
WE JUST RECYCLE THOSE AND 

3549
02:35:22,725 --> 02:35:24,426
PROVIDE THEM WITH SIGNALS TO 

3550
02:35:24,426 --> 02:35:28,731
GROW CARTILAGE AGAIN AND TO 

3551
02:35:28,731 --> 02:35:29,899
PROVIDE A BETTER ENVIRONMENT FOR

3552
02:35:29,899 --> 02:35:31,600
THE CELLS TO DO SO WHICH WAS 

3553
02:35:31,600 --> 02:35:34,169
MENTIONED BY OTHERS AS WELL WE 

3554
02:35:34,169 --> 02:35:39,008
THOUGHT THIS COULD BE A ROLE FOR

3555
02:35:39,008 --> 02:35:41,977
ALOE YES NAYIC.  SO THAT'S WHY 

3556
02:35:41,977 --> 02:35:45,881
WE SAID LET'S COME ONE A 

3557
02:35:45,881 --> 02:35:47,116
TECHNIQUE TO SURGICALLY WORK 

3558
02:35:47,116 --> 02:35:48,951
WITH THE TISSUE AND CHEMICALLY 

3559
02:35:48,951 --> 02:35:55,824
DIGEST IT TO THE LEVEL OF THE 

3560
02:35:55,824 --> 02:35:57,359
CON DRON AND PUT THEM BACK INTO 

3561
02:35:57,359 --> 02:35:59,194
N THE JOINT IN ONE PROCEDURE. 

3562
02:35:59,194 --> 02:36:03,966
AND WE'VE DONE SO NOW IN TWO 

3563
02:36:03,966 --> 02:36:09,071
TRIALS.  IN EUROPE WE COMPLETED 

3564
02:36:09,071 --> 02:36:10,639
THE TWO TRIALS.  AND ONE IN 

3565
02:36:10,639 --> 02:36:13,342
MINNESOTA AND TRANSFORMED THE 

3566
02:36:13,342 --> 02:36:14,877
PRACTICE.  AND AFTER, SEVEN 

3567
02:36:14,877 --> 02:36:16,312
YEARS, FOLLOW UP IN EUROPE AND 

3568
02:36:16,312 --> 02:36:18,347
NOW TWO YEARS FOLLOW UP OF THE 

3569
02:36:18,347 --> 02:36:19,481
SECONDARY COHORT IN THE UNITED 

3570
02:36:19,481 --> 02:36:21,550
STATES I CAN SAY THIS IS A 

3571
02:36:21,550 --> 02:36:25,454
REDUCIBLE -- REPRODUCIBLE 

3572
02:36:25,454 --> 02:36:26,555
CLINICALLY EFFICACIOUS 

3573
02:36:26,555 --> 02:36:29,024
TECHNOLOGY THAT ALLOWS PATIENT 

3574
02:36:29,024 --> 02:36:32,661
LESS PAIN, BETTER QUALITY OF 

3575
02:36:32,661 --> 02:36:33,662
LIFE, FUNCTIONAL OUTCOME SCORES 

3576
02:36:33,662 --> 02:36:36,165
THAT IS NOT ONLY STATISTICALLY 

3577
02:36:36,165 --> 02:36:37,900
SIGNIFICANT AND CLINICALLY 

3578
02:36:37,900 --> 02:36:38,901
SIGNIFICANT AND REPRODUCIBLE 

3579
02:36:38,901 --> 02:36:41,503
BETWEEN CENTERS, BETWEEN 

3580
02:36:41,503 --> 02:36:42,972
CONTINENTS AND SCIENTIFICALLY IN

3581
02:36:42,972 --> 02:36:45,007
EUROPE WE USE BONE MARROW 

3582
02:36:45,007 --> 02:36:48,811
DERIVED ALOE YES NAYIC MSCS. 

3583
02:36:48,811 --> 02:36:50,112
HERE WE USE DIFFERENT.  AND THE 

3584
02:36:50,112 --> 02:36:52,381
CLINICAL OUTCOMES ARE THE SAME. 

3585
02:36:52,381 --> 02:36:55,551
WHICH IS INTERESTING FROM A 

3586
02:36:55,551 --> 02:36:57,820
MANUFACTURING PERSPECTIVE.  SO 

3587
02:36:57,820 --> 02:36:59,989
WHAT DO WE KNOW ABOUT THE 

3588
02:36:59,989 --> 02:37:01,624
PRODUCT?  NOT MUCH EXCEPT THAT 

3589
02:37:01,624 --> 02:37:03,492
WE HAVEN'T HAD ANY SAFETY ISSUES

3590
02:37:03,492 --> 02:37:06,829
AND IN THE EUROPEAN PATIENTS IN 

3591
02:37:06,829 --> 02:37:08,263
33/35 PATIENTS WE WERE ABLE TO 

3592
02:37:08,263 --> 02:37:09,632
GO BACK FOR A SECOND LOOK TO 

3593
02:37:09,632 --> 02:37:11,233
LOOK AT THE TISSUE AND DO VIDEO 

3594
02:37:11,233 --> 02:37:13,102
ANALYSIS TO LOOK AT THE QUALITY 

3595
02:37:13,102 --> 02:37:18,073
OF THE REPAIR AND THE CONDITION 

3596
02:37:18,073 --> 02:37:21,877
OF THE GROWTH AND TO DO BIOPSIES

3597
02:37:21,877 --> 02:37:22,978
AND TO DO DNA TYPING SO WE WERE 

3598
02:37:22,978 --> 02:37:25,981
ABLE TO ANALYZE THE D DNA FROM 

3599
02:37:25,981 --> 02:37:27,449
THE NEWLY GROWN TISSUE. 

3600
02:37:27,449 --> 02:37:30,686
AND WE ONLY FOUND PATIENT'S OWN 

3601
02:37:30,686 --> 02:37:33,455
DNA WHERE WE STARTED WITH 99% 

3602
02:37:33,455 --> 02:37:37,626
ALOE YES NAYIC CELLS AND THAT'S 

3603
02:37:37,626 --> 02:37:40,929
AN INTERESTING FINDING.  SO WHAT

3604
02:37:40,929 --> 02:37:42,531
DO I THINK THE CHALLENGES ARE.  

3605
02:37:42,531 --> 02:37:46,235
I HAVE DONE FIFTEEN YEARS OF 

3606
02:37:46,235 --> 02:37:48,937
TRIALS AND IT SOUNDS STRANGE BUT

3607
02:37:48,937 --> 02:37:52,107
TRUE BY I'VE BEEN REGISTERED IN 

3608
02:37:52,107 --> 02:37:52,608
BOTH.  

3609
02:37:52,608 --> 02:37:55,210
HAVE LEARNED FROM THE TRIALS AND

3610
02:37:55,210 --> 02:37:56,612
EACH TRIAL TEACHES YOU SOMETHING

3611
02:37:56,612 --> 02:37:58,681
YOU WILL DO DIFFERENTLY.  I HAVE

3612
02:37:58,681 --> 02:38:00,249
SEEN GOOD PRODUCTS NOT MAKE IT 

3613
02:38:00,249 --> 02:38:01,884
THROUGH BECAUSE THEY DESIGNED 

3614
02:38:01,884 --> 02:38:03,819
THE TRIAL THAT WAS TOO STRENUOUS

3615
02:38:03,819 --> 02:38:05,387
AND DIFFICULT TO MEET THE BAR 

3616
02:38:05,387 --> 02:38:06,488
EVEN THOUGH THE BAR WOULD HAVE 

3617
02:38:06,488 --> 02:38:09,958
BEEN TYPE A LITTLE TTLE BIT -- A

3618
02:38:09,958 --> 02:38:11,293
LITTLE BIT LOWER. 

3619
02:38:11,293 --> 02:38:16,632
AND THE COMPARATORS ARE 

3620
02:38:16,632 --> 02:38:18,867
WRONG.AND THE REGULATORY 

3621
02:38:18,867 --> 02:38:20,235
AGENCIES SHOULD ALLOWS US TO 

3622
02:38:20,235 --> 02:38:22,571
COME UP WITH BETTER 

3623
02:38:22,571 --> 02:38:23,605
METHODOLOGIES.  I HAVE ALSO SEEN

3624
02:38:23,605 --> 02:38:25,140
WITH INCREASING TECHNOLOGY AND 

3625
02:38:25,140 --> 02:38:29,511
WITH INCREASE IN TIME, CLICK, 

3626
02:38:29,511 --> 02:38:34,650
PLEASE.  THE RESULTS ARE BETTER.

3627
02:38:34,650 --> 02:38:37,052
THIS IS AN IMPROVEMENT.  SO IT 

3628
02:38:37,052 --> 02:38:39,121
WAS THE POTENCY ASSAYS THAT 

3629
02:38:39,121 --> 02:38:40,422
IMPROVED.  IT WAS THE DNA 

3630
02:38:40,422 --> 02:38:41,356
TECHNOLOGY THAT IMPROVED.  IT 

3631
02:38:41,356 --> 02:38:45,060
WAS THE MATRIX BASED SURGICAL 

3632
02:38:45,060 --> 02:38:49,031
TECHNIQUE THAT IMPROVED THE MACI

3633
02:38:49,031 --> 02:38:51,033
OUTCOMES AND IT'S THE ONE STAGE 

3634
02:38:51,033 --> 02:38:53,936
TECHNOLOGIES THAT ALLOW IMMUNE 

3635
02:38:53,936 --> 02:38:54,970
MODULATION AS WELL AS CARTILAGE 

3636
02:38:54,970 --> 02:38:56,572
REGENERATION SO THESE ARE ALL 

3637
02:38:56,572 --> 02:38:57,673
REITERATIONS AND IMPROVEMENTS 

3638
02:38:57,673 --> 02:38:58,474
THAT COME THROUGH TIME.  WHERE 

3639
02:38:58,474 --> 02:39:00,476
ARE THE LIMITATIONS?  AND WHERE 

3640
02:39:00,476 --> 02:39:03,879
ARE THE CHALLENGES I TRY TO SUM 

3641
02:39:03,879 --> 02:39:05,414
THOSE UP.  WE NEED TO PUT OUR 

3642
02:39:05,414 --> 02:39:06,682
HANDS TOGETHER TO MAKE SURE THAT

3643
02:39:06,682 --> 02:39:08,517
MORE GOOD TECHNOLOGIES MAKE IT 

3644
02:39:08,517 --> 02:39:10,185
THROUGH AND DON'T STAY BEHIND 

3645
02:39:10,185 --> 02:39:12,321
THE BAR.  AND I THINK THAT THE 

3646
02:39:12,321 --> 02:39:15,290
ASPECTS TO CONSIDER MANY OF THEM

3647
02:39:15,290 --> 02:39:17,793
HAVE BEEN MENTIONED IS UNIFORM 

3648
02:39:17,793 --> 02:39:20,395
CHARACTERIZATION OF CELLULAR 

3649
02:39:20,395 --> 02:39:21,263
PRODUCTS, DESCRIPTION, TEAM 

3650
02:39:21,263 --> 02:39:22,865
ORGANIZATION AND CENTRALIZED 

3651
02:39:22,865 --> 02:39:25,234
MAYBE EVEN TOPDOWN INITIATIVES 

3652
02:39:25,234 --> 02:39:26,602
SO WE DON'T HAVE TO DO TOO MANY 

3653
02:39:26,602 --> 02:39:27,870
THINGS THE SAME WAY OR DIFFERENT

3654
02:39:27,870 --> 02:39:29,104
WAYS IN DIFFERENT LABS AT 

3655
02:39:29,104 --> 02:39:30,372
DIFFERENT TIMES WITHOUT 

3656
02:39:30,372 --> 02:39:32,875
COMMUNICATING THAT.  I THINK WE 

3657
02:39:32,875 --> 02:39:34,510
SHOULD FIND THE REALLY 

3658
02:39:34,510 --> 02:39:35,778
INNOVATIVE PROJECT AND THE ONE 

3659
02:39:35,778 --> 02:39:37,312
WITH CLINICAL RELEVANCE AND IT'S

3660
02:39:37,312 --> 02:39:38,781
ALWAYS DIFFICULT TO DO THAT AS A

3661
02:39:38,781 --> 02:39:40,315
CLINICIAN BECAUSE YOU'RE TOTALLY

3662
02:39:40,315 --> 02:39:41,617
BIASED TOWARD THE JOINT OR THE 

3663
02:39:41,617 --> 02:39:43,051
ORGAN OR THE DISEASE THAT YOU 

3664
02:39:43,051 --> 02:39:45,954
WANT TO CONQUER I DO THINK THAT 

3665
02:39:45,954 --> 02:39:47,489
THE AGENCY AND NIH BOTH HAVE A 

3666
02:39:47,489 --> 02:39:50,659
ROLE IN PROVIDING US WITH 

3667
02:39:50,659 --> 02:39:52,427
GUIDANCE MORE THAN WITH JUDGMENT

3668
02:39:52,427 --> 02:39:55,230
AND PARTNERING MORE THAN SAYING 

3669
02:39:55,230 --> 02:39:57,099
YES OR NO ONLY.  AND I THINK 

3670
02:39:57,099 --> 02:40:00,369
IT'S BEEN SAID BEFORE BUT I -- 

3671
02:40:00,369 --> 02:40:01,203
FOR US IT'S BEEN REALLY 

3672
02:40:01,203 --> 02:40:02,805
IMPORTANT IF YOU HAVE TIME WITH 

3673
02:40:02,805 --> 02:40:04,907
THE FDA IT'S USUALLY REALLY GOOD

3674
02:40:04,907 --> 02:40:06,308
QUALITY TIME SO WE WANT MORE OF 

3675
02:40:06,308 --> 02:40:10,045
IT EARLIER ON BECAUSE THAT JUST 

3676
02:40:10,045 --> 02:40:10,979
ACCELERATES THE PROCESS AND HAS 

3677
02:40:10,979 --> 02:40:12,748
BEEN A VERY, VERY PLEASANT 

3678
02:40:12,748 --> 02:40:14,449
EXPERIENCE FOR US THOSE ARE THE 

3679
02:40:14,449 --> 02:40:14,983
THOUGHTS WE HAVE FOR THIS 

3680
02:40:14,983 --> 02:40:16,752
PROJECT AND I LOOK FORWARD TO 

3681
02:40:16,752 --> 02:40:20,255
DISCUSSING IT IN THE UPCOMING 

3682
02:40:20,255 --> 02:40:27,529
DAYS, THANK YOU VERY MUCH.

3683
02:40:27,529 --> 02:40:31,033
>> FINAL SPEAKER FOR
TODAY'S 

3684
02:40:31,033 --> 02:40:35,571
SESSION TWO IS TONY ORO.

3685
02:40:35,571 --> 02:40:36,705
>> THANK YOU SO MUCH AGAIN
FOR 

3686
02:40:36,705 --> 02:40:41,710
THE INVITATION, I'M THE 

3687
02:40:41,710 --> 02:40:43,846
CODIRECTOR FOR THE DEFINITIVE 

3688
02:40:43,846 --> 02:40:45,080
CURATIVE MEDICINE.  AND SO I'M 

3689
02:40:45,080 --> 02:40:46,248
GOING TO TALK ABOUT A PROJECT 

3690
02:40:46,248 --> 02:40:48,951
WHICH WAS INITIALLY FUNDED WITH 

3691
02:40:48,951 --> 02:40:51,119
DENNIS AND SUBSEQUENTLY FUNDED 

3692
02:40:51,119 --> 02:40:55,357
BY SERM AND THE DEVELOPMENT OF 

3693
02:40:55,357 --> 02:40:57,125
DEFENSE WITH OTHERS.  IT REALLY 

3694
02:40:57,125 --> 02:41:00,729
IS A -- IT'S DESIGNED TO TREAT 

3695
02:41:00,729 --> 02:41:04,233
NON HEALING WOUNDS IN PATIENTS 

3696
02:41:04,233 --> 02:41:14,776
WITH A -- IT HAS SKIN, DERMIS.  

3697
02:41:16,979 --> 02:41:18,580
AND IT'S -- SO BASICALLY WHAT 

3698
02:41:18,580 --> 02:41:21,984
WE'VE DONE IS WE HAVE DEVELOPED 

3699
02:41:21,984 --> 02:41:25,921
AN AWE TOLL LOW GUS IPS 

3700
02:41:25,921 --> 02:41:26,221
CORRECTION. 

3701
02:41:26,221 --> 02:41:28,123
MAKING THE BANK FOR EACH PATIENT

3702
02:41:28,123 --> 02:41:30,959
TARGETED TO ONE GUIDE AND ONE 

3703
02:41:30,959 --> 02:41:31,226
MUTATION. 

3704
02:41:31,226 --> 02:41:35,130
AND THEN USE THE SKILLS TO 

3705
02:41:35,130 --> 02:41:38,233
DEVELOP THREE DIFFERENT 

3706
02:41:38,233 --> 02:41:41,904
LINEAGES.  ACTIVE DERM WHICH 

3707
02:41:41,904 --> 02:41:45,107
EACH OF THESE INTERACT.  WE USE 

3708
02:41:45,107 --> 02:41:47,910
SINGLE CELL ANALYSIS TO DEFINE 

3709
02:41:47,910 --> 02:41:51,013
THE PRODUCT.  GIVE US BIOMARKERS

3710
02:41:51,013 --> 02:41:53,515
TO THEN BASICALLY DO DELIVER -- 

3711
02:41:53,515 --> 02:41:55,284
IN TERMS OF TISSUE ORGANOIDS 

3712
02:41:55,284 --> 02:41:57,586
ONTO THE SKIN WHICH IS A LOT 

3713
02:41:57,586 --> 02:41:58,787
EASIER TO DO THAN BASICALLY THE 

3714
02:41:58,787 --> 02:42:00,188
HEART OR THE BRAIN BECAUSE IT'S 

3715
02:42:00,188 --> 02:42:01,556
RIGHT HERE IN THE PATIENTS AND 

3716
02:42:01,556 --> 02:42:02,958
THE WOUNDS ARE THERE AS WELL SO 

3717
02:42:02,958 --> 02:42:05,560
WE'VE BEEN ABLE TO DO THIS BY 

3718
02:42:05,560 --> 02:42:06,995
THREE MANUFACTURING.  WITH ONE 

3719
02:42:06,995 --> 02:42:08,730
MUTATION AND ONE GUIDE FOR -- 

3720
02:42:08,730 --> 02:42:11,099
AND THEN ALSO FOR A SEPARATE 

3721
02:42:11,099 --> 02:42:13,368
GUIDE IN RNA MUTATION WE 

3722
02:42:13,368 --> 02:42:16,471
DEVELOPED POTENCY MARKERS FOR 

3723
02:42:16,471 --> 02:42:19,007
GRAFTABILITY AND EFFICACY AND 

3724
02:42:19,007 --> 02:42:21,076
HAVE DONE THREE TO SIX MONTH 

3725
02:42:21,076 --> 02:42:22,611
TOXICOLOGY STUDIES ON OUR 

3726
02:42:22,611 --> 02:42:23,312
ORGANOIDS.  

3727
02:42:23,312 --> 02:42:24,947
SO WITH THE POTENCY AND 

3728
02:42:24,947 --> 02:42:26,782
SKILLABILITY IS THERE.  WE CAN 

3729
02:42:26,782 --> 02:42:29,084
MAKE ENOUGH TO COVER THE BODY 

3730
02:42:29,084 --> 02:42:32,888
THREE TIMES OVER FOR EACH 

3731
02:42:32,888 --> 02:42:34,456
PATIENT AND WE HAVE A MEETING 

3732
02:42:34,456 --> 02:42:36,058
WITH THE FDA NEXT WEEK AND WE 

3733
02:42:36,058 --> 02:42:38,293
LOOK FORWARD TO THE DISCUSSION 

3734
02:42:38,293 --> 02:42:40,395
WITH THEM ON THE PROJECT.  SO 

3735
02:42:40,395 --> 02:42:42,931
WHAT HAVE WE LEARNED? WE LEARNED

3736
02:42:42,931 --> 02:42:44,766
BASICALLY THAT AS THE SAME 

3737
02:42:44,766 --> 02:42:45,367
THEMES THAT YOU HEARD ABOUT 

3738
02:42:45,367 --> 02:42:49,504
OTHER OVER THE MORNING THAT IT'S

3739
02:42:49,504 --> 02:42:50,372
THE COST OF MANUFACTURING. 

3740
02:42:50,372 --> 02:42:53,575
THE BESPOKE IPS BANKS FOR EACH 

3741
02:42:53,575 --> 02:42:55,143
PATIENT AND THE LINE TO LINE 

3742
02:42:55,143 --> 02:42:56,278
VARIABILITY WHICH THEN INCREASE 

3743
02:42:56,278 --> 02:42:58,580
THE COST, TIME OF MANUFACTURING.

3744
02:42:58,580 --> 02:43:00,749
WE HAVE GONE A LONG WAY IN 

3745
02:43:00,749 --> 02:43:03,752
UNDERSTANDING HOW IPS CELL 

3746
02:43:03,752 --> 02:43:05,454
DIFFERENTIATES INTO THREE 

3747
02:43:05,454 --> 02:43:06,321
LINEAGES AND THEN BASICALLY INTO

3748
02:43:06,321 --> 02:43:09,057
THE INTERACTION BETWEEN THE 

3749
02:43:09,057 --> 02:43:10,425
DIFFERENT LINEAGE TO MAKE 

3750
02:43:10,425 --> 02:43:12,995
DIFFERENT SKIN ORGAN NOISE.  

3751
02:43:12,995 --> 02:43:15,564
HOWEVER, IT STILL NEEDS TO BE 

3752
02:43:15,564 --> 02:43:17,065
BETTER. 

3753
02:43:17,065 --> 02:43:19,701
ALSO, IN TERMS OF THE DENNIS 

3754
02:43:19,701 --> 02:43:20,769
TALKED ABOUT THIS MORNING ABOUT 

3755
02:43:20,769 --> 02:43:25,073
THE ONE ID POLICY.  AGAIN, THE 

3756
02:43:25,073 --> 02:43:29,644
FDAS  WANTS US TO PROVIDE THE 

3757
02:43:29,644 --> 02:43:31,613
POLICY. 

3758
02:43:31,613 --> 02:43:32,547
BY PROVIDING TWO DIFFERENT 

3759
02:43:32,547 --> 02:43:33,648
GUIDES FOR TWO DIFFERENT 

3760
02:43:33,648 --> 02:43:35,984
MUTATIONS AND THE IPS 

3761
02:43:35,984 --> 02:43:37,552
INTERMEDIATE WE CAN PROVIDE THE 

3762
02:43:37,552 --> 02:43:39,187
GUIDANCE THEY NEED TO ALLOW THEM

3763
02:43:39,187 --> 02:43:43,525
TO SOFTEN THE ONE GUIDE ONE RND 

3764
02:43:43,525 --> 02:43:47,796
POLICY.  I THINK THE NEXT THING 

3765
02:43:47,796 --> 02:43:51,166
IS -- WE'RE MAKING IT AUTOLOGOUS

3766
02:43:51,166 --> 02:43:52,634
BECAUSE WE WANT IT TO BE INERT 

3767
02:43:52,634 --> 02:43:54,569
BUT FOR THE BANKS WHICH HAVE -- 

3768
02:43:54,569 --> 02:43:57,372
A DECREASED COST OF GOODS, THE 

3769
02:43:57,372 --> 02:43:59,641
ISSUE IS IMMUNOLOGIC ACTIVITY.  

3770
02:43:59,641 --> 02:44:01,376
SO FOR THE NEXT SLIDE, SO WHAT 

3771
02:44:01,376 --> 02:44:03,612
DO WE NEED IN TERMS OF RESEARCH?

3772
02:44:03,612 --> 02:44:05,213
IN TERMS OF COST AND SCALE OF 

3773
02:44:05,213 --> 02:44:06,515
MANUFACTURING WE NEED TO 

3774
02:44:06,515 --> 02:44:07,783
AUTOMATE THE MANUFACTURING 

3775
02:44:07,783 --> 02:44:09,518
PROCEDURES FOR THESE PATIENTS.  

3776
02:44:09,518 --> 02:44:10,485
WE NEED TO BASICALLY UNDERSTAND 

3777
02:44:10,485 --> 02:44:13,688
USING AS WE TALKED ABOUT IPS 

3778
02:44:13,688 --> 02:44:15,891
WHAT I CALL MAPS OF THE LYNN 

3779
02:44:15,891 --> 02:44:18,326
YAMS SO WE KNOW HOW THE LINEAGE 

3780
02:44:18,326 --> 02:44:19,761
INTERACT IN THE ORGANOIDS. 

3781
02:44:19,761 --> 02:44:22,497
WE KNOW HOW TO PREDICT WHAT 

3782
02:44:22,497 --> 02:44:23,532
THEY'LL DO IN THE TISSUE BECAUSE

3783
02:44:23,532 --> 02:44:25,967
WE KNOW WHAT THEIR STATE IS AT 

3784
02:44:25,967 --> 02:44:28,770
THE TIME OF THE PRODUCT.  AS 

3785
02:44:28,770 --> 02:44:30,072
WELL AS BASICALLY IDENTIFYING 

3786
02:44:30,072 --> 02:44:32,407
AND UPDATING AND WORKING WITH 

3787
02:44:32,407 --> 02:44:36,778
THE SCIENTIFIC COVER FOR OUR -- 

3788
02:44:36,778 --> 02:44:39,414
FOR SIMPLIFYING AND ACCELERATING

3789
02:44:39,414 --> 02:44:40,148
MANUFACTURING POLICIES AND 

3790
02:44:40,148 --> 02:44:42,651
THAT'S REALLY UP TO US TO DO 

3791
02:44:42,651 --> 02:44:46,288
THAT AND LASTLY ACTIVITY FOR 

3792
02:44:46,288 --> 02:44:47,823
ALLOGENEIC BANKS WE NEED TO TALK

3793
02:44:47,823 --> 02:44:50,559
ABOUT HOW TO MODIFY THE PRODUCT 

3794
02:44:50,559 --> 02:44:56,965
OR THE PATIENT.  AND I THANK 

3795
02:44:56,965 --> 02:45:00,235
EVERYONE FOR OUR PROJECT.  IT'S 

3796
02:45:00,235 --> 02:45:06,641
A LARGE GROUP.  AND WE'VE ALL 

3797
02:45:06,641 --> 02:45:07,609
CONTRIBUTED SO THANKS VERY MUCH.

3798
02:45:07,609 --> 02:45:09,544
>> I WANT TO THANK ALL OUR

3799
02:45:09,544 --> 02:45:11,313
SESSION TWO SPEAKERS.  WE'RE 

3800
02:45:11,313 --> 02:45:13,014
GOING TO OPEN UP THE SESSION TO 

3801
02:45:13,014 --> 02:45:14,616
QUESTIONS FROM THE FLOOR.  AND 

3802
02:45:14,616 --> 02:45:15,784
MARTHA IS GOING TO LEAD THE 

3803
02:45:15,784 --> 02:45:26,128
DISCUSSION AND Q&A.

3804
02:45:30,432 --> 02:45:33,502
>> HEY.  OUTSTANDING.  I
REALLY 

3805
02:45:33,502 --> 02:45:35,370
ENJOYED HEARING ABOUT SCIENCE 

3806
02:45:35,370 --> 02:45:37,105
THAT I'M NOT TOO UP-TO-DATE ON 

3807
02:45:37,105 --> 02:45:40,008
SO I WOULD LOVE TO HEAR FROM YOU

3808
02:45:40,008 --> 02:45:42,377
FIRST BEFORE I DIVE INTO MAYBE 

3809
02:45:42,377 --> 02:45:45,046
IDENTIFYING MY QUESTIONS OR 

3810
02:45:45,046 --> 02:45:46,014
IDENTIFYING SPECIFIC THINGS.  I 

3811
02:45:46,014 --> 02:45:48,350
DO THINK THAT WE HAVE SOME 

3812
02:45:48,350 --> 02:45:49,584
THINGS IN THIS SESSION THAT ARE 

3813
02:45:49,584 --> 02:45:51,786
SIMILAR TO THE OTHER SESSION.  

3814
02:45:51,786 --> 02:45:55,624
SO IF ANYONE WOULD LIKE TO ASK 

3815
02:45:55,624 --> 02:45:59,060
ANY SPECIFIC SCIENTIFIC 

3816
02:45:59,060 --> 02:46:00,362
QUESTIONS FIRST BASED ON WHAT 

3817
02:46:00,362 --> 02:46:02,831
YOU HEARD TODAY OR WE COULD DIVE

3818
02:46:02,831 --> 02:46:13,074
RIGHT INTO THEMES.  YES?

3819
02:46:13,074 --> 02:46:14,309
>> I JUST WANT TO ECHO MY 

3820
02:46:14,309 --> 02:46:17,812
COLLEAGUE IN THE FIELD.  SO MY 

3821
02:46:17,812 --> 02:46:20,749
WORK FOCUS ON HUMAN RETINAL 

3822
02:46:20,749 --> 02:46:22,584
IMPLEMENTATION INTO A RODENT 

3823
02:46:22,584 --> 02:46:25,086
MODEL SO I SAID ONE OF THE 

3824
02:46:25,086 --> 02:46:27,155
CHALLENGES WE HAVE OR I HAVE IS 

3825
02:46:27,155 --> 02:46:29,291
WE CAN HAVE A LOW CELL SURVIVAL 

3826
02:46:29,291 --> 02:46:31,526
AND ALSO VERY LOW CELL 

3827
02:46:31,526 --> 02:46:34,930
INTEGRATION BECAUSE THERE'S A 

3828
02:46:34,930 --> 02:46:40,001
LAYER MEMBRANE, THE DONOR CELL 

3829
02:46:40,001 --> 02:46:42,504
TO THE LAYER.  FOR THE DONOR 

3830
02:46:42,504 --> 02:46:44,873
CELL WE USE THE INJECTION AND SO

3831
02:46:44,873 --> 02:46:47,509
TO OVERCOME THIS BARRIER, IT'S A

3832
02:46:47,509 --> 02:46:51,746
POSSIBLE WAY.  ONE IS TO USE THE

3833
02:46:51,746 --> 02:46:53,949
ENZYMATIC DIGESTION TO DIGEST IT

3834
02:46:53,949 --> 02:46:55,183
THERE BECAUSE THIS IS ACTUALLY A

3835
02:46:55,183 --> 02:46:58,987
CELLULAR METRIC.  HOWEVER, 

3836
02:46:58,987 --> 02:47:01,056
IMMUNE ACCURATE INFORMATION 

3837
02:47:01,056 --> 02:47:03,758
MIGHT HAPPEN SOMETIMES.  AND 

3838
02:47:03,758 --> 02:47:04,926
EVERYTHING IS MECHANIC REMOVAL 

3839
02:47:04,926 --> 02:47:08,964
OF THIS MEMBRANE BUT LIKE IN 

3840
02:47:08,964 --> 02:47:12,567
CLINIC PEOPLE USE A PATIENT YOU 

3841
02:47:12,567 --> 02:47:16,004
CAN DO THIS.  HOWEVER IT'S ALSO 

3842
02:47:16,004 --> 02:47:19,107
CONSTANT RISK BECAUSE YOU CAN 

3843
02:47:19,107 --> 02:47:21,543
REMOVE THIS MEMBRANE.  SO IN 

3844
02:47:21,543 --> 02:47:24,613
COLLABORATION WITH THE PHYSICIAN

3845
02:47:24,613 --> 02:47:27,048
SCIENTIST IN TOM AND JOHNS 

3846
02:47:27,048 --> 02:47:30,151
HOPKINS WE TRIED TO DEVELOP A 

3847
02:47:30,151 --> 02:47:34,589
METHOD TO APPROVE TO REMOVE THIS

3848
02:47:34,589 --> 02:47:35,690
MEMBRANE TO GET BETTER 

3849
02:47:35,690 --> 02:47:36,725
EFFICIENCY.  YEAH, I JUST WANT 

3850
02:47:36,725 --> 02:47:40,195
TO ECHO MY COLLEAGUE IN THIS 

3851
02:47:40,195 --> 02:47:44,899
FIELD, YEAH.  THANK YOU.

3852
02:47:44,899 --> 02:47:55,043
>> DAN?

3853
02:47:56,111 --> 02:47:58,013
>> I WANTED TO FOLLOW UP, 

3854
02:47:58,013 --> 02:47:58,980
ANOTHER COMMON THEME WHICH IS 

3855
02:47:58,980 --> 02:48:00,982
SHARING OF INFORMATION.  YOU 

3856
02:48:00,982 --> 02:48:02,284
MENTIONED THAT IT'S VERY 

3857
02:48:02,284 --> 02:48:04,152
DIFFICULT FOR ALL THE RIGHT 

3858
02:48:04,152 --> 02:48:06,087
REASONS TO GET PROPRIETARY 

3859
02:48:06,087 --> 02:48:06,721
INFORMATION FROM INDUSTRY TRIALS

3860
02:48:06,721 --> 02:48:09,357
AND THINGS LIKE THAT.  BUT THIS,

3861
02:48:09,357 --> 02:48:10,859
I THINK THIS IS VERY IMPORTANT 

3862
02:48:10,859 --> 02:48:13,328
IF WE CAN FIGURE OUT -- AND RUN 

3863
02:48:13,328 --> 02:48:15,297
AROUND WITH SOMETHING NOW SO TWO

3864
02:48:15,297 --> 02:48:18,466
THOUGHTS.  ONE IS PROBABLY 

3865
02:48:18,466 --> 02:48:20,101
IMPOSSIBLE IS TO WHETHER OR NOT 

3866
02:48:20,101 --> 02:48:21,269
THERE COULD BE ANY INFLUENCE OF 

3867
02:48:21,269 --> 02:48:24,639
THIS GROUP IN THE CONSORTIUM ON 

3868
02:48:24,639 --> 02:48:30,245
MAKING CLINICAL TRIALS.GOV MORE 

3869
02:48:30,245 --> 02:48:31,946
ACCOUNTABLE.  THERE ARE SO MANY 

3870
02:48:31,946 --> 02:48:34,015
TRIALS.  CELL BASED THERAPY.  

3871
02:48:34,015 --> 02:48:36,184
GENE THERAPIES AND THE LIKE THAT

3872
02:48:36,184 --> 02:48:37,485
YOU JUST NEVER SEE THE LIGHT OF 

3873
02:48:37,485 --> 02:48:38,987
THE INFORMATION BUT THE OTHER 

3874
02:48:38,987 --> 02:48:41,156
WHICH I THINK MIGHT BE MORE 

3875
02:48:41,156 --> 02:48:44,626
PRACTICAL AND REALISTIC IS 

3876
02:48:44,626 --> 02:48:45,593
PATIENT REGISTRIES FOR CLINICAL 

3877
02:48:45,593 --> 02:48:46,928
INVESTIGATIONS THAT ARE 

3878
02:48:46,928 --> 02:48:49,331
ADDRESSING A COMMON THEME, AND 

3879
02:48:49,331 --> 02:48:52,000
THROUGH -- IF IT'S GOING TO BE 

3880
02:48:52,000 --> 02:48:53,735
WITH GOVERNMENTAL SUPPORT LET'S 

3881
02:48:53,735 --> 02:48:56,338
PUT TOGETHER REGISTRIES, THE 

3882
02:48:56,338 --> 02:48:57,872
BONE TRANSPLANT PEOPLE HAVE DONE

3883
02:48:57,872 --> 02:49:01,676
THAT SUCCESSFULLY, THE ONCOLOGY 

3884
02:49:01,676 --> 02:49:02,277
INVESTIGATORS OF COURSE HAVE 

3885
02:49:02,277 --> 02:49:03,912
DONE THAT TREMENDOUSFULLY 

3886
02:49:03,912 --> 02:49:05,680
SUCCESSFULLY WE CAN DO THE SAME 

3887
02:49:05,680 --> 02:49:08,149
THING AND WHAT IT GETS TO IS I 

3888
02:49:08,149 --> 02:49:09,884
THINK REALLY STILL A PRESSING 

3889
02:49:09,884 --> 02:49:11,386
QUESTION WHICH IS PATIENT 

3890
02:49:11,386 --> 02:49:12,120
PHENOTYPE.  

3891
02:49:12,120 --> 02:49:14,956
AND IT'S NOT ONE SIZE FITS ALL 

3892
02:49:14,956 --> 02:49:16,958
SO IF WE BUILD INTO REGISTRIES 

3893
02:49:16,958 --> 02:49:18,360
NOT JUST CLINICAL OUTCOME BUT GO

3894
02:49:18,360 --> 02:49:20,662
BACK TO BIOMARKERS, GO BACK TO 

3895
02:49:20,662 --> 02:49:22,564
THE IDEA THAT ARE THERE 

3896
02:49:22,564 --> 02:49:25,834
PREDICTIVE THINGS THAT WE COULD 

3897
02:49:25,834 --> 02:49:28,470
OBTAIN ON DAY NEGATIVE ONE, ON 

3898
02:49:28,470 --> 02:49:29,471
WHATEVER TRIAL YOU'RE GOING TO 

3899
02:49:29,471 --> 02:49:30,605
DO THAT YOU CAN LINK WITH 

3900
02:49:30,605 --> 02:49:34,309
SUCCESS AND THEN BUILD A BETTER 

3901
02:49:34,309 --> 02:49:40,515
MOUSE TRAP.

3902
02:49:40,515 --> 02:49:43,485
>> ON THAT NOTE IN TERMS
OF THE 

3903
02:49:43,485 --> 02:49:45,487
CLINICAL TRIALS.GOV AS WELL AS 

3904
02:49:45,487 --> 02:49:47,689
GETTING PHENOTYPE AND PREDICTIVE

3905
02:49:47,689 --> 02:49:48,990
MARKERS WHERE IS ARTIFICIAL 

3906
02:49:48,990 --> 02:49:52,026
INTELLIGENCE IN TERMS OF THE 

3907
02:49:52,026 --> 02:49:52,460
PREDICTIVE NATURE?

3908
02:49:52,460 --> 02:49:54,729
>> WAITING TO HAPPEN.  I
MEAN, 

3909
02:49:54,729 --> 02:49:55,997
THIS IS WHERE WE CAN BE SMART 

3910
02:49:55,997 --> 02:49:59,634
ABOUT IT.  AI AND MACHINE BASED 

3911
02:49:59,634 --> 02:50:00,702
LEARNING CLEARLY IS HERE AND IS 

3912
02:50:00,702 --> 02:50:02,771
GOING TO BE WAITING IN THE 

3913
02:50:02,771 --> 02:50:04,339
FUTURE.  WE, AGAIN, IF WE CAN 

3914
02:50:04,339 --> 02:50:05,607
FIGURE OUT AS A GROUP HOW TO 

3915
02:50:05,607 --> 02:50:07,375
SUPPORT THE TYPE OF 

3916
02:50:07,375 --> 02:50:09,444
INVESTIGATIONS THAT WOULD MAKE 

3917
02:50:09,444 --> 02:50:12,080
THIS EFFECTIVE FOR CLINICAL 

3918
02:50:12,080 --> 02:50:13,581
TRIALS BUT NOT ONLY CLINICAL 

3919
02:50:13,581 --> 02:50:16,050
TRIALS IT'S COME UP A COUPLE 

3920
02:50:16,050 --> 02:50:17,552
TIMES EARLIER IN THE 

3921
02:50:17,552 --> 02:50:18,486
CONVERSATION IN MANUFACTURING.  

3922
02:50:18,486 --> 02:50:19,354
ALL RIGHT.  SO I THINK THERE'S A

3923
02:50:19,354 --> 02:50:23,124
LOT OF ROOM FOR THAT.

3924
02:50:23,124 --> 02:50:30,231
>> OKAY.  THANK YOU. 
RICHARD?

3925
02:50:30,231 --> 02:50:35,069
>> JUST ONE POINT RELATED
TO 

3926
02:50:35,069 --> 02:50:37,238
CLINICALTRIALS.GOV THERE'S A 

3927
02:50:37,238 --> 02:50:39,174
SMALL NONPROFIT CALLED TRUE 

3928
02:50:39,174 --> 02:50:42,944
TRIALS WHICH JUST LAUNCHED AT 

3929
02:50:42,944 --> 02:50:45,313
MESA ABOUT A MONTH AGO.  AND 

3930
02:50:45,313 --> 02:50:48,750
WITH TALKING TO FDA, THEY'RE 

3931
02:50:48,750 --> 02:50:51,853
ONLY GOING TO LIST TRIALS WHO 

3932
02:50:51,853 --> 02:50:55,890
HAVE INDS OR CELL THERAPIES AND 

3933
02:50:55,890 --> 02:50:58,726
SO THE IDEA IS TO -- IT'S A, AS 

3934
02:50:58,726 --> 02:51:03,565
I SAID, A NONPROFIT, TO KIND OF 

3935
02:51:03,565 --> 02:51:08,603
ANSWER THAT QUESTION BETWEEN THE

3936
02:51:08,603 --> 02:51:10,805
MANDATE OF CLINICALTRIALS.GOV 

3937
02:51:10,805 --> 02:51:14,275
AND THE PATIENT NEED TO FIND 

3938
02:51:14,275 --> 02:51:23,985
TRIALS THAT ARE ONGOING.

3939
02:51:23,985 --> 02:51:25,720
>> I'M FROM
SLOAN-KETTERING.  I 

3940
02:51:25,720 --> 02:51:27,355
WANTED TO FOLLOW UP ON THE NEED 

3941
02:51:27,355 --> 02:51:30,058
FOR BETTER UNDERSTANDS A WAY TO 

3942
02:51:30,058 --> 02:51:33,061
PRODUCT PERFORMS IN VIVO AND YOU

3943
02:51:33,061 --> 02:51:34,762
HEARD.  I THINK THAT COULD BE AN

3944
02:51:34,762 --> 02:51:38,166
AREA WHERE THERE ARE COMMON 

3945
02:51:38,166 --> 02:51:40,435
PROBLEMS THAT OCCUR JUST THE 

3946
02:51:40,435 --> 02:51:44,372
WORK IN THE BRAIN.  AND YOU HAVE

3947
02:51:44,372 --> 02:51:45,874
PARKINSON'S DISEASE AND THE 

3948
02:51:45,874 --> 02:51:49,444
CRISPR SCREENING AND THEY FIND 

3949
02:51:49,444 --> 02:51:52,080
THE PATHWAY AND THAT CAN BE 

3950
02:51:52,080 --> 02:51:55,483
EASILY PHARMACOLOGICALLY 

3951
02:51:55,483 --> 02:51:56,584
INHIBITED.  AND I'M PRETTY SURE 

3952
02:51:56,584 --> 02:52:00,788
THAT HAPPENS FOR MANY TISSUES.  

3953
02:52:00,788 --> 02:52:02,290
IF THERE WERE INITIATIVES IN 

3954
02:52:02,290 --> 02:52:04,759
THAT AREA TO LOOK AT WHAT ARE 

3955
02:52:04,759 --> 02:52:06,327
THE COMMON PROBLEMS OF SURVIVAL 

3956
02:52:06,327 --> 02:52:08,663
I THINK THAT WOULD BE SOMETHING 

3957
02:52:08,663 --> 02:52:10,365
THAT WOULD BENEFIT MORE WITH THE

3958
02:52:10,365 --> 02:52:11,399
GROUPS AND THERE HASN'T BEEN 

3959
02:52:11,399 --> 02:52:13,968
ENOUGH FOCUS ON THAT SO FAR.

3960
02:52:13,968 --> 02:52:17,238
>> SO AS A CONSORTIUM OR A
GROUP

3961
02:52:17,238 --> 02:52:19,474
EFFORT YOU THINK THAT MIGHT BE 

3962
02:52:19,474 --> 02:52:20,341
ADDRESSED A LITTLE BIT MORE?

3963
02:52:20,341 --> 02:52:23,144
>> YES.  I MEAN, IT COULD
BE 

3964
02:52:23,144 --> 02:52:24,779
JUST SIMPLY GROUPS THAT ARE 

3965
02:52:24,779 --> 02:52:26,648
ALREADY DOING THAT.  THEY COULD 

3966
02:52:26,648 --> 02:52:29,017
SHARE MORE INFORMATION.  WE HAVE

3967
02:52:29,017 --> 02:52:31,319
A CONSORTIUM GROUP FROM JAPAN, 

3968
02:52:31,319 --> 02:52:33,087
FROM EUROPE, FROM THE U.S. THAT 

3969
02:52:33,087 --> 02:52:35,823
ALL HELPED EACH OTHER GET INTO 

3970
02:52:35,823 --> 02:52:38,059
CLINIC AND NOW WE ARE ALREADY IN

3971
02:52:38,059 --> 02:52:39,761
THE PHASE ONE TRIAL SO FAR AND I

3972
02:52:39,761 --> 02:52:41,095
THINK IT HELPED ALL OF THEM TO 

3973
02:52:41,095 --> 02:52:43,698
BE IN A COMPETITIVE BUT 

3974
02:52:43,698 --> 02:52:45,667
COLLABORATIVE EFFORT WHERE THERE

3975
02:52:45,667 --> 02:52:46,935
IS, LIKE, I DON'T KNOW WHAT IS 

3976
02:52:46,935 --> 02:52:48,236
THE RIGHT TERM BUT WHERE 

3977
02:52:48,236 --> 02:52:50,805
EVERYONE SHARES A LIST THERE AND

3978
02:52:50,805 --> 02:52:51,940
ALSO ACROSS FIELDS BECAUSE OF 

3979
02:52:51,940 --> 02:52:56,177
THE PATHWAY I MENTIONED IS GOING

3980
02:52:56,177 --> 02:52:58,680
TO BE LIKE THIS.  AND IF ONE 

3981
02:52:58,680 --> 02:53:00,315
GETS THAT INFORMATION, AND GETS 

3982
02:53:00,315 --> 02:53:03,685
ACCESS TO THAT INFORMATION, YOU 

3983
02:53:03,685 --> 02:53:05,086
KNOW, EARLY, AND THEY 

3984
02:53:05,086 --> 02:53:06,421
SPECIFICALLY CALL AND LOOKING AT

3985
02:53:06,421 --> 02:53:08,690
THAT AREA NOT JUST MAKING THE 

3986
02:53:08,690 --> 02:53:11,593
RIGHT CELL BUT ACTUALLY 

3987
02:53:11,593 --> 02:53:12,493
INTEGRATION IS LIMITED I THINK 

3988
02:53:12,493 --> 02:53:14,996
THERE'S A LOT OF SCIENTIFIC 

3989
02:53:14,996 --> 02:53:17,065
KNOWLEDGE THAT IS TO SOME EXTENT

3990
02:53:17,065 --> 02:53:18,866
MISSING BUT WE COULD HAVE A 

3991
02:53:18,866 --> 02:53:21,069
SIMPLE SOLUTION THAT WE CAN 

3992
02:53:21,069 --> 02:53:23,304
UNDERSTAND A LITTLE BIT BETTER.

3993
02:53:23,304 --> 02:53:25,206
>> THANKS SO MUCH JUST FOR
WHAT 

3994
02:53:25,206 --> 02:53:26,374
LAUREN JUST TALKED ABOUT IN 

3995
02:53:26,374 --> 02:53:28,476
TERMS OF SHARING DATA.  SO ONE 

3996
02:53:28,476 --> 02:53:32,046
OF THE CLUES WE GOT FROM -- TO 

3997
02:53:32,046 --> 02:53:36,818
MAKE MULTILINEAGE TISSUE 

3998
02:53:36,818 --> 02:53:40,054
ORGANOIDS WAS WORK THAT WAS 

3999
02:53:40,054 --> 02:53:42,790
SHARED BY LAWRENCE IN THE 

4000
02:53:42,790 --> 02:53:45,860
DIFFERENTIATION TO DEFINE THE 

4001
02:53:45,860 --> 02:53:48,630
PRODUCT IN SINGLE CELL.  WHICH 

4002
02:53:48,630 --> 02:53:53,601
CAN JUST DEPOSIT INTO DB GAP OR 

4003
02:53:53,601 --> 02:53:56,804
GEO, AND THE PUBLICLY AVAILABLE.

4004
02:53:56,804 --> 02:53:58,906
AND CS MAPS WHICH IS ALSO 

4005
02:53:58,906 --> 02:54:01,075
PUBLICLY AVAILABLE AND ALSO USED

4006
02:54:01,075 --> 02:54:03,678
LAWRENCE'S DATA FOR US AND HELP 

4007
02:54:03,678 --> 02:54:07,015
TO MAKE US SKIN.  USING OTHER 

4008
02:54:07,015 --> 02:54:08,049
PEOPLE'S DATA TO MAKE TISSUES 

4009
02:54:08,049 --> 02:54:12,520
AND USING, AGAIN, AI APPROACHES.

4010
02:54:12,520 --> 02:54:13,755
I THINK REALLY IS THE WAY 

4011
02:54:13,755 --> 02:54:15,123
FORWARD.  BUT I HAVE TO SHARE 

4012
02:54:15,123 --> 02:54:17,058
THE DATA.  IT'S ALREADY OUT 

4013
02:54:17,058 --> 02:54:19,027
THERE AND I THINK THAT'S JUST A 

4014
02:54:19,027 --> 02:54:21,763
FOLLOW UP ON WHAT LAWRENCE SAID.

4015
02:54:21,763 --> 02:54:24,399
>> AND MAYBE ACCESSIBLE
BUT NOT 

4016
02:54:24,399 --> 02:54:27,402
DIGESTIBLE IS THAT WHAT YOU'RE 

4017
02:54:27,402 --> 02:54:30,338
SAYING?  IN TERMS OF DB GAP AND 

4018
02:54:30,338 --> 02:54:30,538
OTHER.

4019
02:54:30,538 --> 02:54:31,939
>> I THINK THE QUESTION
FOR US 

4020
02:54:31,939 --> 02:54:35,877
IS -- SO WHAT IS THE -- SO THE 

4021
02:54:35,877 --> 02:54:38,346
MINIMAL UNIT FOR CHEMICALS IS --

4022
02:54:38,346 --> 02:54:43,451
IS THAT ALWAYS -- MRI.  FOR 

4023
02:54:43,451 --> 02:54:45,319
CELLS WHAT'S THE MINIMAL UNIT?  

4024
02:54:45,319 --> 02:54:50,458
AND I'D ARGUE IT'S EPIGENETIC 

4025
02:54:50,458 --> 02:54:52,627
STATE AND SO BY USING THAT AS A 

4026
02:54:52,627 --> 02:54:53,728
COMMON LANGUAGE WE CAN THEN 

4027
02:54:53,728 --> 02:54:57,131
SHARE OUR DATA ACROSS TISSUE 

4028
02:54:57,131 --> 02:54:59,033
PLATFORM CELL STATE TRAJECTORY 

4029
02:54:59,033 --> 02:55:01,469
AND ALSO THEN MAKE PREDICTIVE 

4030
02:55:01,469 --> 02:55:02,603
MARKERS FOR WHERE THE PRODUCT IS

4031
02:55:02,603 --> 02:55:05,840
NOW AND WHAT IT WILL DO IN THE 

4032
02:55:05,840 --> 02:55:07,909
TISSUE WHERE WE CAN SCREEN FOR 

4033
02:55:07,909 --> 02:55:10,578
THINGS LIKE CELL.  I THINK 

4034
02:55:10,578 --> 02:55:12,980
THAT'S WHERE WE ARE IN THE 

4035
02:55:12,980 --> 02:55:16,184
TECHNOLOGY RIGHT NOW.

4036
02:55:16,184 --> 02:55:18,352
>> THANKS.

4037
02:55:18,352 --> 02:55:19,954
>> ONE MORE FOLLOW UP
AGAIN 

4038
02:55:19,954 --> 02:55:21,656
BECAUSE MANY OF YOU PROBABLY 

4039
02:55:21,656 --> 02:55:23,257
KNOW THERE ARE NOW BIG CELL 

4040
02:55:23,257 --> 02:55:26,627
ATLAS PROJECTS ONGOING FROM CCE 

4041
02:55:26,627 --> 02:55:29,030
AND OTHERS AND THE PROBLEM IS 

4042
02:55:29,030 --> 02:55:31,833
SOME OF THOSE IS NOT THEIR 

4043
02:55:31,833 --> 02:55:33,701
PRIMARY RESULTS AND IF YOU MATCH

4044
02:55:33,701 --> 02:55:35,169
THEM.  BUT THERE'S A LOT OF, 

4045
02:55:35,169 --> 02:55:36,838
AGAIN, AREA WHERE WE, FOR 

4046
02:55:36,838 --> 02:55:38,673
EXAMPLE, TRIED TO BUILD THAT AND

4047
02:55:38,673 --> 02:55:39,707
THAT YOU CAN VERY EASILY TAKE 

4048
02:55:39,707 --> 02:55:43,878
YOUR DATA, PLUCK THEM IN AND IT 

4049
02:55:43,878 --> 02:55:46,447
GIVES THE QUALITY SCORES AND YOU

4050
02:55:46,447 --> 02:55:47,782
KNOW HOW CLOSE YOU ARE TO MAYBE 

4051
02:55:47,782 --> 02:55:48,816
THE GOLD STANDARD OF THE CELL 

4052
02:55:48,816 --> 02:55:50,251
AND THAT'S AN OPPORTUNITY NOW 

4053
02:55:50,251 --> 02:55:51,385
THAT'S COMING UP BECAUSE THERE'S

4054
02:55:51,385 --> 02:55:54,322
BEEN A HUGE INVESTMENT FROM CCI 

4055
02:55:54,322 --> 02:55:55,823
IN ORDER TO BUILD THOSE ATLASES 

4056
02:55:55,823 --> 02:55:57,125
AND THAT'S JUST GOING TO 

4057
02:55:57,125 --> 02:56:00,661
EEXPLODE AND SO WE SOMEHOW, EVEN

4058
02:56:00,661 --> 02:56:03,030
WE HAD A BINGE OF RELEASE 

4059
02:56:03,030 --> 02:56:04,932
CRITERIA MARKERS AND THEY'RE 

4060
02:56:04,932 --> 02:56:07,935
VERY, VERY LIMITED TO DEFINE A 

4061
02:56:07,935 --> 02:56:08,536
PRODUCT.  ON THE OTHER HAND, 

4062
02:56:08,536 --> 02:56:09,670
THERE'S THIS WEALTH OF 

4063
02:56:09,670 --> 02:56:11,439
INFORMATION WHERE WE CAN GO 

4064
02:56:11,439 --> 02:56:12,974
VERY, VERY DEEP AND I THINK HOW 

4065
02:56:12,974 --> 02:56:14,909
DO TO CLOSE THAT GAP IN MY 

4066
02:56:14,909 --> 02:56:16,310
OPINION IS A BIG QUESTION THAT 

4067
02:56:16,310 --> 02:56:19,714
THE FDA NEEDS TO HELP US TOO TO 

4068
02:56:19,714 --> 02:56:23,284
ADVANCE THOSE IN THOSE COMPLEX 

4069
02:56:23,284 --> 02:56:24,318
FIELDS.  I THINK THERE'S MORE 

4070
02:56:24,318 --> 02:56:26,954
EFFORT NEEDED BUT THERE'S A LOT 

4071
02:56:26,954 --> 02:56:30,892
OF DATA OUT THERE AND WE CAN 

4072
02:56:30,892 --> 02:56:34,695
MAKE THAT MORE ACCESSIBLE AND 

4073
02:56:34,695 --> 02:56:38,366
MAKE IT EASILY TOO TO GIVE YOU 

4074
02:56:38,366 --> 02:56:46,007
SCORES.  THAT'S ON THE CELL 

4075
02:56:46,007 --> 02:56:56,217
SIDE, YEAH.

4076
02:56:59,654 --> 02:57:00,755
>> I HAVE A QUESTION FOR
THE 

4077
02:57:00,755 --> 02:57:02,857
SCIENTIST.  DO YOU THINK WE KNOW

4078
02:57:02,857 --> 02:57:05,059
OR CAN IDENTIFY THE 

4079
02:57:05,059 --> 02:57:05,993
CHARACTERISTICS OF THE VARIANCE 

4080
02:57:05,993 --> 02:57:09,664
DIFFERENT CELLS SUCH AS SURVIVAL

4081
02:57:09,664 --> 02:57:13,067
FACTORS AS YOU MENTIONED OR 

4082
02:57:13,067 --> 02:57:14,602
ENGRAFTMENT AND PROCESS 

4083
02:57:14,602 --> 02:57:16,537
OUTGROWTH THAT ARE IMPORTANT FOR

4084
02:57:16,537 --> 02:57:17,605
REGENERATIVE MEDICINE SO THIS 

4085
02:57:17,605 --> 02:57:20,107
SEEMS TO BE A VERY LIMITED SET. 

4086
02:57:20,107 --> 02:57:21,776
THAT MAY NOT APPLY TO THE ATLAS 

4087
02:57:21,776 --> 02:57:24,612
OF FACTORS OR CHARACTERISTICS OF

4088
02:57:24,612 --> 02:57:26,747
THE CELLS THAT WILL DRIVE THEIR 

4089
02:57:26,747 --> 02:57:27,915
SUCCESS ACROSS DIFFERENT TIS

4090
02:57:27,915 --> 02:57:32,253
TISSUES.  AND JUST TO ADD FOR 

4091
02:57:32,253 --> 02:57:34,055
THAT, GETTING THOSE CATEGORIES 

4092
02:57:34,055 --> 02:57:36,190
FIRST MAYBE WOULD BE A STEP 

4093
02:57:36,190 --> 02:57:46,734
TOWARDS MORE AI ANALYSIS AFTER

4094
02:57:52,540 --> 02:57:55,877
>> IS ANSWER IS YES.  WE
TOOK 

4095
02:57:55,877 --> 02:57:57,778
BASICALLY THE DIFFERENTIATION 

4096
02:57:57,778 --> 02:57:59,547
LINE FOR LINE VARIANT IN THE 

4097
02:57:59,547 --> 02:58:02,650
FIVE DIFFERENT PATIENT LICENSE. 

4098
02:58:02,650 --> 02:58:04,185
GRAFTABILITY STUDIES, TAKE THE 

4099
02:58:04,185 --> 02:58:07,221
ANALYSIS AND MAP THE CLUSTERS 

4100
02:58:07,221 --> 02:58:08,890
WITH GRAFTABILITY, THERE'S TWO 

4101
02:58:08,890 --> 02:58:11,993
OF THEM THAT ACTUALLY ARE 

4102
02:58:11,993 --> 02:58:13,928
LOCALIZED USING THE MARKERS TO 

4103
02:58:13,928 --> 02:58:15,763
THE FINAL CELL PRODUCT BUT FOR 

4104
02:58:15,763 --> 02:58:20,101
POTENCY AND GRAFTABILITY 

4105
02:58:20,101 --> 02:58:30,645
MARKERS.  THAT'S DOABLE TODAY.  

4106
02:58:41,522 --> 02:58:43,457
WE CIRCUMSTRENGTH OTHER PROBLEMS

4107
02:58:43,457 --> 02:58:45,860
THAT PEOPLE HAVE BUT IT'S 

4108
02:58:45,860 --> 02:58:53,067
CERTAINLY IN ASSAY.

4109
02:58:53,067 --> 02:58:55,403
>> I THINK IT'S DIFFICULT
TO GO 

4110
02:58:55,403 --> 02:58:56,971
TOO DEEP INTO THE WEEDS WITH 

4111
02:58:56,971 --> 02:58:57,872
THIS DISCUSSION BUT IN SOME 

4112
02:58:57,872 --> 02:59:01,542
AREAS I THINK WE KNOW.  IT'S AN 

4113
02:59:01,542 --> 02:59:02,677
OBVIOUS MEASURE.  EITHER THEY 

4114
02:59:02,677 --> 02:59:03,678
SURVIVE OR THEY DON'T AND YOU 

4115
02:59:03,678 --> 02:59:05,579
CAN TRY TO FIND THAT STATE BUT A

4116
02:59:05,579 --> 02:59:07,682
LOT OF IT IS ALSO EMPIRICAL AND 

4117
02:59:07,682 --> 02:59:09,317
WE DON'T KNOW WE NEED TO LEARN 

4118
02:59:09,317 --> 02:59:13,587
WHAT IS THE RIGHT STAGE OF EACH 

4119
02:59:13,587 --> 02:59:15,423
OF THOSE FUNCTIONS.  WHATEVER 

4120
02:59:15,423 --> 02:59:16,857
THE FUNCTION IS.  YOU CAN ONLY 

4121
02:59:16,857 --> 02:59:18,592
DO THAT IF YOU HAVE A 

4122
02:59:18,592 --> 02:59:20,194
WELL-DEFINED PRODUCT.  IF WE 

4123
02:59:20,194 --> 02:59:22,396
JUST TRY MANY, MANY TIMES 

4124
02:59:22,396 --> 02:59:23,764
WITHOUT HAVING ENOUGH 

4125
02:59:23,764 --> 02:59:26,100
INFORMATION TO THE PROCESS.  IF 

4126
02:59:26,100 --> 02:59:28,936
YOU CAN DO IT MORE PREDICTIVE 

4127
02:59:28,936 --> 02:59:30,471
AND IDENTIFY THE IMMEDIATE 

4128
02:59:30,471 --> 02:59:33,074
STAGES AND DISASSEMBLE THE RIGHT

4129
02:59:33,074 --> 02:59:34,709
CELL TYPES YOU CAN DO IT MUCH 

4130
02:59:34,709 --> 02:59:36,844
MORE PREDICTIVE AND IT'S A 

4131
02:59:36,844 --> 02:59:38,879
TRANSLATIONAL HAT.  HOW DO YOU 

4132
02:59:38,879 --> 02:59:41,615
MAKE THAT SCIENCE PRESENTABLE 

4133
02:59:41,615 --> 02:59:42,850
AND INTRODUCIBLE AND FOLLOWING 

4134
02:59:42,850 --> 02:59:44,719
ALL THE QC THAT YOU CAN ACTUALLY

4135
02:59:44,719 --> 02:59:46,454
BRING TO THE FDA THAT CAN BE 

4136
02:59:46,454 --> 02:59:54,228
APPROVED?

4137
02:59:54,228 --> 02:59:55,596
>> SO, QUESTION BECAUSE I
ALSO 

4138
02:59:55,596 --> 02:59:59,133
THINK THAT WE NEED MARKERS THAT 

4139
02:59:59,133 --> 03:00:01,736
WOULD SAY WHETHER A CELL'S GOING

4140
03:00:01,736 --> 03:00:03,704
TO BE TUMISA HER GENERALIC OR 

4141
03:00:03,704 --> 03:00:12,380
GOING INTO A STATE OF SENES

4142
03:00:12,380 --> 03:00:12,680
SENESCENCE.

4143
03:00:12,680 --> 03:00:13,614
>> I THINK -- WE DEVELOPED
A 

4144
03:00:13,614 --> 03:00:17,518
WHOLE GENOME SEQUENCING PIPELINE

4145
03:00:17,518 --> 03:00:22,623
AND THEN THE PANEL
RELEASED>> I 

4146
03:00:22,623 --> 03:00:23,257
WHOLE GENOME SEQUENCING PIPELINE

4147
03:00:23,257 --> 03:00:23,824
AND THEN THE PANEL RELEASED 

4148
03:00:23,824 --> 03:00:27,495
CRITERION FOR OUR PRODUCT.  WE 

4149
03:00:27,495 --> 03:00:32,299
HAVE DONE SEQUENCING AND THE 

4150
03:00:32,299 --> 03:00:34,435
PATIENTS GET SQUAMOUS CELL IF 

4151
03:00:34,435 --> 03:00:35,936
YOU DON'T TREAT THEIR WOUNDS.  

4152
03:00:35,936 --> 03:00:40,074
THEY ALL HAVE PRECANCER REGIONS.

4153
03:00:40,074 --> 03:00:42,043
YOU CAN FIND THE BANKS THAT ARE 

4154
03:00:42,043 --> 03:00:43,044
CLEAN AND GIVE THEM SOMETHING 

4155
03:00:43,044 --> 03:00:44,712
BETTER THAN WHAT THEY HAD 

4156
03:00:44,712 --> 03:00:48,549
BEFORE.  THAT'S AN EXAMPLE OF 

4157
03:00:48,549 --> 03:00:49,083
THAT.

4158
03:00:49,083 --> 03:00:50,651
>> OPTIMIZING THE ANIMAL
MODEL 

4159
03:00:50,651 --> 03:00:51,752
SYSTEM IT SEEMS TO ME THAT 

4160
03:00:51,752 --> 03:00:54,221
THAT'S A MAJOR THEME ALSO FROM 

4161
03:00:54,221 --> 03:00:55,723
THIS GROUP IS THAT OPTIMIZATION 

4162
03:00:55,723 --> 03:00:58,059
OF THE MODEL SYSTEM IS WHAT'S 

4163
03:00:58,059 --> 03:00:58,993
NEEDED AND THE KNOWLEDGE THAT 

4164
03:00:58,993 --> 03:01:01,295
YOU'RE TALKING ABOUT IS WHAT 

4165
03:01:01,295 --> 03:01:03,831
WOULD BE NECESSARY TO OPTIMIZE 

4166
03:01:03,831 --> 03:01:04,131
YOUR MODEL.

4167
03:01:04,131 --> 03:01:07,568
>> THIS IS PREANIMAL. 
THIS IS 

4168
03:01:07,568 --> 03:01:09,537
ALL TISSUE ORGANOIDS SO YOU CAN 

4169
03:01:09,537 --> 03:01:11,906
DO A -- IT'S -- JUST, I JUST 

4170
03:01:11,906 --> 03:01:14,542
WANT TO -- RATHER THAN -- I 

4171
03:01:14,542 --> 03:01:20,247
THINK DOING A TON OF INSILLY KOE

4172
03:01:20,247 --> 03:01:22,516
ANALYSIS.  AI.  WE CAN DO SO 

4173
03:01:22,516 --> 03:01:22,950
MUCH.

4174
03:01:22,950 --> 03:01:23,217
>> RIGHT.

4175
03:01:23,217 --> 03:01:26,087
>> IN THE END YOU NEED TO
DO THE

4176
03:01:26,087 --> 03:01:26,787
FUNCTIONAL STUFF AND THAT'S 

4177
03:01:26,787 --> 03:01:27,755
IMPORTANT.  BUT I THINK THERE'S 

4178
03:01:27,755 --> 03:01:30,691
A -- I THINK WE'RE MISSING A LOT

4179
03:01:30,691 --> 03:01:33,894
OF THE OPPORTUNITY TO DO A LOT 

4180
03:01:33,894 --> 03:01:39,500
OF STUFF THAT'S THERE.

4181
03:01:39,500 --> 03:01:42,470
>> IT GETS SO EASY TO BE
LOST IN

4182
03:01:42,470 --> 03:01:43,838
CERTAIN QUESTIONS.  THIS HAS 

4183
03:01:43,838 --> 03:01:45,005
BEEN MY EXPERIENCE WITH THIS 

4184
03:01:45,005 --> 03:01:47,074
DEVELOPED TWO IPS LINES THAT 

4185
03:01:47,074 --> 03:01:48,909
WE'VE BEEN TRYING TO GET 

4186
03:01:48,909 --> 03:01:49,944
REGULATORY APPROVAL FOR AND 

4187
03:01:49,944 --> 03:01:52,079
WHOLE GENOME SEQUENCING HAS 

4188
03:01:52,079 --> 03:01:55,516
TLULT BEEN  ABSOLUTELY BEEN A 

4189
03:01:55,516 --> 03:01:58,519
PART OF THE TESTING FOR THAT. 

4190
03:01:58,519 --> 03:02:01,088
WHERE'S THE LINE DRAWN?  THERE 

4191
03:02:01,088 --> 03:02:04,658
ARE CERTAIN GENES, CERTAIN 

4192
03:02:04,658 --> 03:02:05,826
VARIANCES THAT ARE PROHIBITIVE 

4193
03:02:05,826 --> 03:02:08,262
OF, YOU KNOW, AROUND THE LINES, 

4194
03:02:08,262 --> 03:02:09,830
BUT, HOW MANY VARIANCE AND HOW 

4195
03:02:09,830 --> 03:02:11,799
MANY GENES IS CONSIDERED 

4196
03:02:11,799 --> 03:02:12,433
ACCEPTABLE?  NOW HAVING SAID 

4197
03:02:12,433 --> 03:02:13,334
THAT OBVIOUSLY YOU'RE GOING TO 

4198
03:02:13,334 --> 03:02:16,737
GO FORWARD AND DO A SAFETY STUDY

4199
03:02:16,737 --> 03:02:18,472
AND TUMISA HER YES IN THIS 

4200
03:02:18,472 --> 03:02:19,440
CASETY STUDIES WHERE WEATHER YOU

4201
03:02:19,440 --> 03:02:21,775
LIKE IT OR NOT AND THOSE WILL 

4202
03:02:21,775 --> 03:02:23,144
HAVE CERTAIN OUTCOMES. 

4203
03:02:23,144 --> 03:02:25,846
AND IT WOULD BE HELPFUL TO HAVE 

4204
03:02:25,846 --> 03:02:27,481
SOME INITIATIVE THAT'S AI-BASE 

4205
03:02:27,481 --> 03:02:28,382
THAT HAD WILL JUST SORT OF 

4206
03:02:28,382 --> 03:02:30,818
DEFINE A BASELINE OF WHAT 

4207
03:02:30,818 --> 03:02:32,553
CONSTITUTES A HEALTHY GENOME FOR

4208
03:02:32,553 --> 03:02:33,954
A CELL THERAPY PRODUCT.  

4209
03:02:33,954 --> 03:02:44,498
AT LEAST IN AN ALOE YES NAYIC.

4210
03:02:44,899 --> 03:02:48,502
>> I APPRECIATE YOUR
INSIGHTS.  

4211
03:02:48,502 --> 03:02:51,038
YOU CAN LOOK AT ALL THE GENETICS

4212
03:02:51,038 --> 03:02:52,806
INFORMATION BY I APPRECIATE THE 

4213
03:02:52,806 --> 03:02:55,376
POINT ABOUT, YOU KNOW, ANIMAL 

4214
03:02:55,376 --> 03:02:59,180
MODEL BECAUSE, AGAIN, THE CELL 

4215
03:02:59,180 --> 03:03:02,483
ENVIRONMENT IS WHAT KIND OF 

4216
03:03:02,483 --> 03:03:04,084
ENVIRONMENT YOU OBSERVE IS 

4217
03:03:04,084 --> 03:03:06,420
DEPENDENT ON WHICH MODEL YOU 

4218
03:03:06,420 --> 03:03:08,255
PASSED.  USING DIFFERENT ANIMAL 

4219
03:03:08,255 --> 03:03:09,390
MODEL YOU CAN HAVE DIFFERENT 

4220
03:03:09,390 --> 03:03:11,125
RESULTS.  I THINK -- THE AI 

4221
03:03:11,125 --> 03:03:13,494
CAN'T BE AS GOOD AS THE DATA 

4222
03:03:13,494 --> 03:03:15,329
INPUTTING SO, YOU KNOW, I THINK 

4223
03:03:15,329 --> 03:03:17,298
THAT IS CERTAINLY GOING TO BE 

4224
03:03:17,298 --> 03:03:26,006
IMPORTANT METRICS TO CONSIDER.

4225
03:03:26,006 --> 03:03:28,042
>> YOU KNOW, I COULDN'T
RESIST, 

4226
03:03:28,042 --> 03:03:29,777
THIS IS RICHARD, COMMENTING 

4227
03:03:29,777 --> 03:03:32,980
ABOUT NON-CLINICAL -- WHAT 

4228
03:03:32,980 --> 03:03:35,082
PEOPLE CALL PRECLINICAL.  I WISH

4229
03:03:35,082 --> 03:03:36,850
WE COULD CALL IT NON-CLINICAL.  

4230
03:03:36,850 --> 03:03:38,686
IT ISN'T ALWAYS ANIMAL STUDIES. 

4231
03:03:38,686 --> 03:03:41,855
I THINK IN THE AGENCY IT'S IN 

4232
03:03:41,855 --> 03:03:44,758
THEIR GUIDANCE FOR NON-CLINICAL 

4233
03:03:44,758 --> 03:03:46,527
STUDIES FOR GENE THERAPIES THEY 

4234
03:03:46,527 --> 03:03:48,162
POINT OUT IT DOESN'T ALWAYS HAVE

4235
03:03:48,162 --> 03:03:49,930
TO BE AN ANIMAL STUDY BUT AN 

4236
03:03:49,930 --> 03:03:52,666
IDEA OF EXPLAINING YOUR STUDIES 

4237
03:03:52,666 --> 03:03:56,637
AND WHAT YOUR END POINTS ARE AND

4238
03:03:56,637 --> 03:03:57,871
HOW THEY SUPPORT CLINICAL TRIALS

4239
03:03:57,871 --> 03:03:59,440
AND DEVELOPMENT IS IMPORTANT AND

4240
03:03:59,440 --> 03:04:01,308
I HAVE GOT ONE QUESTION RELATED.

4241
03:04:01,308 --> 03:04:04,078
YOU SAID, WELL, OF COURSE YOU DO

4242
03:04:04,078 --> 03:04:05,379
TWO STUDIES WHETHER YOU WANT TO 

4243
03:04:05,379 --> 03:04:08,048
OR NOT IS THERE ANYONE IN THE 

4244
03:04:08,048 --> 03:04:10,050
ROOM WHO'S ACTUALLY FOUND 

4245
03:04:10,050 --> 03:04:12,086
SOMETHING USEFUL DOING ANIMAL 

4246
03:04:12,086 --> 03:04:13,687
TUMOR IN THIS CASETY STUDIES IN 

4247
03:04:13,687 --> 03:04:17,324
THE LAST 30 YEARS BECAUSE IF 

4248
03:04:17,324 --> 03:04:23,397
THERE ISN'T, MAYBE TAKING SOME 

4249
03:04:23,397 --> 03:04:27,201
OF THE DATA THAT WE WERE ABLE TO

4250
03:04:27,201 --> 03:04:31,071
DO WITH THE MULTIPARAMETERS TO 

4251
03:04:31,071 --> 03:04:34,141
PROVIDE JUST AS MUCH 

4252
03:04:34,141 --> 03:04:35,542
PREDICTABILITY OF THE POTENTIAL 

4253
03:04:35,542 --> 03:04:39,013
BAD EFFECT OF A TUMOR.  

4254
03:04:39,013 --> 03:04:42,016
THAN DOING A TUMOR GENESISTY 

4255
03:04:42,016 --> 03:04:52,526
STUDY WOULD MAKE MORE SENSE.

4256
03:04:58,432 --> 03:05:01,068
>> I HAVE NO CLUE OVER THE
LAST 

4257
03:05:01,068 --> 03:05:03,270
30 YEARS I KNOW THERE ARE IPS 

4258
03:05:03,270 --> 03:05:04,371
STUDIES THAT HAVE BEEN DONE THAT

4259
03:05:04,371 --> 03:05:07,441
HAVE LOOKED AT THRESHOLDS OF 

4260
03:05:07,441 --> 03:05:09,376
RESIDUAL IPSCS THAT WOULD RESULT

4261
03:05:09,376 --> 03:05:12,179
IN TUMORS IN ANIMALS AND I 

4262
03:05:12,179 --> 03:05:17,551
BELIEVE THEY FOUND A THRESHOLD. 

4263
03:05:17,551 --> 03:05:19,253
IN MY OWN ACTION WITH THE AGENCY

4264
03:05:19,253 --> 03:05:21,522
WE TRIED TO GET AWAY WITH AT 

4265
03:05:21,522 --> 03:05:23,891
LEAST DOING IN VITRO SOFT TYPE 

4266
03:05:23,891 --> 03:05:26,360
ASSAYS AND WE WERE TOLD WE HAD 

4267
03:05:26,360 --> 03:05:27,728
TO DO FULL BLOWN RAT STUDIES 

4268
03:05:27,728 --> 03:05:29,096
WHICH MAKES SENSE TO ME AT THIS 

4269
03:05:29,096 --> 03:05:30,297
STAGE THERE AREN'T A WHOLE LOT 

4270
03:05:30,297 --> 03:05:34,835
OF IPSC STUDIES GOING ON BUT 

4271
03:05:34,835 --> 03:05:38,405
THERE HAS BEEN TUMORS FORMED AND

4272
03:05:38,405 --> 03:05:48,682
FOUND.  SO. . .

4273
03:05:54,188 --> 03:06:02,262
>> (SPEAKER FAR FROM MIC).

4274
03:06:02,262 --> 03:06:12,606
>> ASK THE AGENCY.

4275
03:06:21,048 --> 03:06:22,282
>> TO FOLLOW UP ON SOME OF
THIS 

4276
03:06:22,282 --> 03:06:27,388
DISCUSSION I THINK ONE OF OUR 

4277
03:06:27,388 --> 03:06:27,988
PRESENTERS, AT LEAST I WROTE 

4278
03:06:27,988 --> 03:06:32,059
THIS DOWN WAS COMBINING RELEVANT

4279
03:06:32,059 --> 03:06:34,428
MODELS WITH ORGAN ON CHIP.  WHO 

4280
03:06:34,428 --> 03:06:36,463
WAS IT THAT SAID THAT?  

4281
03:06:36,463 --> 03:06:37,798
ROSEMARY, YOU DIDN'T SAY THAT.  

4282
03:06:37,798 --> 03:06:41,335
YOU DIDN'T COME UP HERE AND GIVE

4283
03:06:41,335 --> 03:06:46,840
A TALK.  GO AHEAD.  DOESN'T TO 

4284
03:06:46,840 --> 03:06:49,276
SAY SOMETHING?  YEAH.  WELL, 

4285
03:06:49,276 --> 03:06:50,911
OKAY.  ALL RIGHT.  YEAH.  SO I 

4286
03:06:50,911 --> 03:06:53,881
THOUGHT THAT WAS A THEME THAT 

4287
03:06:53,881 --> 03:06:55,549
WAS INTERESTING.  AND ALONG WITH

4288
03:06:55,549 --> 03:06:57,951
THAT THEME CAME, YOU KNOW, THE 

4289
03:06:57,951 --> 03:07:01,054
CELL DELIVERY SYSTEMS AND 

4290
03:07:01,054 --> 03:07:04,057
TRACKING AND ALL THAT GOOD 

4291
03:07:04,057 --> 03:07:07,428
STUFF.  ANYBODY ELSE HAVE ANY 

4292
03:07:07,428 --> 03:07:14,301
CONTRIBUTIONS TO THAT THEME?  

4293
03:07:14,301 --> 03:07:15,302
OKA

4294
03:07:15,302 --> 03:07:15,502
OKAY.

4295
03:07:15,502 --> 03:07:16,670
>> SO THE POINT THAT I
GUESS I 

4296
03:07:16,670 --> 03:07:19,440
WAS TRYING TO MAKE AND I WOULD 

4297
03:07:19,440 --> 03:07:21,775
REALLY LOVE OTHER PEOPLE TO 

4298
03:07:21,775 --> 03:07:23,343
CHIME IN WAS THAT THERE'S A 

4299
03:07:23,343 --> 03:07:25,679
CERTAIN SET OF CHARACTERISTICS 

4300
03:07:25,679 --> 03:07:28,048
THAT COME OUT OF DIFFERENT TYPES

4301
03:07:28,048 --> 03:07:30,083
OF STUDIES.  AND, YOU KNOW, WHAT

4302
03:07:30,083 --> 03:07:33,487
WE NEED TO DO IS I THINK CAMPING

4303
03:07:33,487 --> 03:07:34,421
ON BUILDING ON SOMETHING 

4304
03:07:34,421 --> 03:07:36,190
SOMEBODY ELSE SAID WHICH WAS, 

4305
03:07:36,190 --> 03:07:37,691
YOU KNOW, TRYING TO DEFINE THE 

4306
03:07:37,691 --> 03:07:39,660
MOST IMPORTANT CHARACTERISTICS. 

4307
03:07:39,660 --> 03:07:41,862
TRYING TO DEFINE THE MOST 

4308
03:07:41,862 --> 03:07:43,564
IMPORTANT DATA POINTS.  EVERY 

4309
03:07:43,564 --> 03:07:45,299
ONE OF US IS GOING TO HAVE OUR 

4310
03:07:45,299 --> 03:07:48,669
OWN BIASES TO WHAT'S THE MOST 

4311
03:07:48,669 --> 03:07:50,204
IMPORTANT.  SO I THINK 

4312
03:07:50,204 --> 03:07:51,772
THERE'S -- THERE SHOULD BE A 

4313
03:07:51,772 --> 03:07:53,941
PRACTICAL WAY TO SORT THESE OUT 

4314
03:07:53,941 --> 03:07:56,510
AT LEAST AS WE GET CLOSER AND 

4315
03:07:56,510 --> 03:07:58,312
CLOSER TO THAT MORE KNOWLEDGE 

4316
03:07:58,312 --> 03:08:00,013
BASE, MORE INFORMATION, GREATER 

4317
03:08:00,013 --> 03:08:01,248
UTILITY OF THE INFORMATION WE 

4318
03:08:01,248 --> 03:08:02,716
GET.  BUT WE HAVE TO START 

4319
03:08:02,716 --> 03:08:05,052
LOOKING AT IT IN AN UNBIASED 

4320
03:08:05,052 --> 03:08:05,986
FASHION AND THAT'S ONE OF THE 

4321
03:08:05,986 --> 03:08:07,988
WAYS THAT AI CAN REALLY HELP US 

4322
03:08:07,988 --> 03:08:11,458
IS THE MORE DATA WE HAVE THE 

4323
03:08:11,458 --> 03:08:13,293
MORE INTEROPERATIVE IT IS THE 

4324
03:08:13,293 --> 03:08:15,829
MORE LOGICALLY IT CAN MAKE 

4325
03:08:15,829 --> 03:08:20,667
PREDICTIONS FOR US AND I HAVE A 

4326
03:08:20,667 --> 03:08:21,935
LITTLE MORE TO SAY ABOUT THAT 

4327
03:08:21,935 --> 03:08:27,040
TODAY BUT THE POINT IS THAT WE 

4328
03:08:27,040 --> 03:08:30,577
SHOULD COLLABORATE AS AN OPEN 

4329
03:08:30,577 --> 03:08:31,879
ENVIRONMENT AS WE CAN.  TO BE 

4330
03:08:31,879 --> 03:08:34,414
ABLE TO REACH OUT TO PEOPLE WHO 

4331
03:08:34,414 --> 03:08:35,649
HAVE INFORMATION THAT COULD BE 

4332
03:08:35,649 --> 03:08:36,984
VERY HELPFUL TO US OTHER THAN 

4333
03:08:36,984 --> 03:08:38,986
KEEPING THESE SILOS IN PLACE.

4334
03:08:38,986 --> 03:08:40,420
>> RIGHT.

4335
03:08:40,420 --> 03:08:41,054
>> BECAUSE THAT'S NOT
GOING TO 

4336
03:08:41,054 --> 03:08:42,789
BE USEFUL.  IT'S INTERESTING 

4337
03:08:42,789 --> 03:08:44,625
THAT I HAVE HEARD PEOPLE SAY, 

4338
03:08:44,625 --> 03:08:46,560
WHAT ARE THE IMPORTANT 

4339
03:08:46,560 --> 03:08:48,328
CHARACTERISTICS?  YOU KNOW, WE 

4340
03:08:48,328 --> 03:08:51,598
DON'T KNOW YET.  BUT IN THE 

4341
03:08:51,598 --> 03:08:52,666
WORLD OF MANUFACTURING THAT'S 

4342
03:08:52,666 --> 03:08:53,967
CALLED A CRITICAL QUALITY 

4343
03:08:53,967 --> 03:08:55,102
ATTRIBUTE AND THOSE ARE THINGS 

4344
03:08:55,102 --> 03:08:56,803
THAT WE HAVE TO LOOK FOR AND 

4345
03:08:56,803 --> 03:08:58,338
SEARCH FOR.  ONE OF THE THINGS 

4346
03:08:58,338 --> 03:08:59,773
THAT HAVE AN IMPACT ON THE 

4347
03:08:59,773 --> 03:09:02,476
OUTCOMES THAT WE'RE LOOKING AT. 

4348
03:09:02,476 --> 03:09:04,044
AND, YOU KNOW, THERE'S 

4349
03:09:04,044 --> 03:09:07,314
DEFINITELY NOT ONE SIZE FITS 

4350
03:09:07,314 --> 03:09:07,614
ALL.

4351
03:09:07,614 --> 03:09:10,918
>> THANK YOU.  I DID WANT
TO 

4352
03:09:10,918 --> 03:09:13,487
MENTION THAT RECURRENT THEME BUT

4353
03:09:13,487 --> 03:09:16,123
A LITTLE BIT OF A TWIST WAS 

4354
03:09:16,123 --> 03:09:18,458
EDUCATION OR WORKFORCE 

4355
03:09:18,458 --> 03:09:20,627
DEVELOPMENT.  I KNOW ARMY HAS A 

4356
03:09:20,627 --> 03:09:23,864
WHOLE ARM COMPONENT OF THAT AND 

4357
03:09:23,864 --> 03:09:27,401
THE INITIATIVE.  BUT SOMEONE 

4358
03:09:27,401 --> 03:09:28,602
SAID SOMETHING ABOUT 

4359
03:09:28,602 --> 03:09:31,004
CROSSCUTTING FOR INVESTIGATORS 

4360
03:09:31,004 --> 03:09:33,073
SO SILOED EXPERTISE.  NOT BEING 

4361
03:09:33,073 --> 03:09:37,210
ABLE TO TALK TO ONE ANOTHER IN 

4362
03:09:37,210 --> 03:09:40,447
REALTIME.  DO INVESTIGATORS 

4363
03:09:40,447 --> 03:09:41,114
ESTABLISH -- IN ADDITION TO 

4364
03:09:41,114 --> 03:09:42,916
CURRICULUM CHANGES FOR THE 

4365
03:09:42,916 --> 03:09:44,384
STUDENT, BUT DO INVESTIGATORS 

4366
03:09:44,384 --> 03:09:47,888
THAT ARE LOOKING TO STAY IN THE 

4367
03:09:47,888 --> 03:09:52,292
RN FIELD DO THEY NEED ADDITIONAL

4368
03:09:52,292 --> 03:09:54,394
TRAINING, EDUCATION?  OKAY?  

4369
03:09:54,394 --> 03:09:56,530
I'VE RAISED SEVERAL HANDS.

4370
03:09:56,530 --> 03:09:57,965
THANK YOU FOR CALLING
OUT 

4371
03:09:57,965 --> 03:10:01,568
THAT THAT'S AN ASPECT OF THESE 

4372
03:10:01,568 --> 03:10:02,736
MANUFACTURING INNOVATION 

4373
03:10:02,736 --> 03:10:04,705
INSTITUTES BUT WE NEED TO 

4374
03:10:04,705 --> 03:10:06,340
REMEMBER IT'S ALSO REALLY KEY 

4375
03:10:06,340 --> 03:10:08,542
ASPECT IT'S BEEN THERE FOR 

4376
03:10:08,542 --> 03:10:10,444
DECADES AT THE NATIONAL SCIENCE 

4377
03:10:10,444 --> 03:10:11,278
FOUNDATION THROUGH THEIR 

4378
03:10:11,278 --> 03:10:12,346
ENGINEERING RESOURCE CENTERS AND

4379
03:10:12,346 --> 03:10:14,648
THE ONES THAT ARE IN THIS SPACE.

4380
03:10:14,648 --> 03:10:16,817
THERE ARE A FEW OF THEM IN THIS 

4381
03:10:16,817 --> 03:10:18,151
SPACE AND SO THEY HAVE BEEN 

4382
03:10:18,151 --> 03:10:20,520
DEVELOPING THESE PROGRAMS FOR 

4383
03:10:20,520 --> 03:10:22,055
YEARS AND SOME OF THE OTHER -- 

4384
03:10:22,055 --> 03:10:26,193
THE MMIS ARE DOING THEM AND 

4385
03:10:26,193 --> 03:10:26,860
THERE ARE OTHER ORGANIZATIONS 

4386
03:10:26,860 --> 03:10:29,296
THAT ARE FOCUSED IN THIS AREA 

4387
03:10:29,296 --> 03:10:30,631
BECAUSE ANYTIME ANYBODY TRIES TO

4388
03:10:30,631 --> 03:10:32,966
DO THIS STUFF AT A HIGHER LEVEL 

4389
03:10:32,966 --> 03:10:35,902
AT A GREATER SCALE THEY BUMP 

4390
03:10:35,902 --> 03:10:37,371
AGAINST -- THEY BUMP UP AGAINST 

4391
03:10:37,371 --> 03:10:38,538
THIS WORKFORCE DEVELOPMENT THING

4392
03:10:38,538 --> 03:10:40,507
RIGHT AWAY AT MULTIPLE LEVELS AS

4393
03:10:40,507 --> 03:10:42,409
YOU POINTED OUT YOU NEED TO 

4394
03:10:42,409 --> 03:10:44,077
EDUCATE THE TECHNICIANS THAT ARE

4395
03:10:44,077 --> 03:10:45,979
PUSHING THE BUTTONS AND RUNNING 

4396
03:10:45,979 --> 03:10:47,147
THE MACHINES BUT YOU ALSO HAVE 

4397
03:10:47,147 --> 03:10:49,916
TO GET THE UPPER LEVEL 

4398
03:10:49,916 --> 03:10:50,917
INVESTIGATORS TALKING TO EACH 

4399
03:10:50,917 --> 03:10:54,388
OTHER ACROSS THE BARRIERS.  AND 

4400
03:10:54,388 --> 03:10:56,757
I HAVE TO ADMIT THE NIH HAS NOT 

4401
03:10:56,757 --> 03:11:00,694
BEEN PARTICULARLY GOOD AT THIS 

4402
03:11:00,694 --> 03:11:11,071
KIND OF THING BUT THE 

4403
03:13:45,692 --> 03:13:46,726
SO, I'M ARON MARQUITZ.

4404
03:13:46,726 --> 03:13:49,296
CANDACE KERR FROM
NIAID, AND

4405
03:13:49,296 --> 03:13:52,332
I'M INVOLVED IN THE IN-DEPTH

4406
03:13:52,332 --> 03:13:52,799
CELL CHARACTERIZATION.

4407
03:13:52,799 --> 03:13:53,834
>> THANK YOU.

4408
03:13:53,834 --> 03:13:54,501
ALL RIGHT.

4409
03:13:54,501 --> 03:13:56,837
SO, I THINK WE'LL STICK WITH THE

4410
03:13:56,837 --> 03:13:59,072
SAME FORMAT HERE, AND I WILL

4411
03:13:59,072 --> 03:14:00,173
CALL UP THE FIRST SPEAKER AND

4412
03:14:00,173 --> 03:14:04,945
THE ONES ON DECK.

4413
03:14:04,945 --> 03:14:08,448
FIRST UP IS DAN WEISS AND ON

4414
03:14:08,448 --> 03:14:13,208
DECK IS TYLER RAM.

4415
03:14:13,208 --> 03:14:18,504
THANK YOU TO THE
ORGANIZERS, A PHENOMENAL
MEETING.

4416
03:14:18,504 --> 03:14:19,705
I'M PROFESSOR OF MEDICINE,

4417
03:14:19,705 --> 03:14:21,040
UNIVERSITY OF VERMONT IN

4418
03:14:21,040 --> 03:14:25,077
PULMONARY AND CRITICAL CARE.

4419
03:14:25,077 --> 03:14:27,747
I'M AN ACADEMICIAN, LONGSTANDING

4420
03:14:27,747 --> 03:14:28,714
INTEREST IN LUNG REGENERATIVE

4421
03:14:28,714 --> 03:14:29,749
MEDICINE, HERE AS REPRESENTATIVE

4422
03:14:29,749 --> 03:14:31,651
OF THE INTERNATIONAL SOCIETY OF

4423
03:14:31,651 --> 03:14:32,752
CELL AND GENE THERAPY, WHERE

4424
03:14:32,752 --> 03:14:35,488
I'VE BEEN THE FORMER LONG-TERM

4425
03:14:35,488 --> 03:14:38,558
CHIEF SCIENTIFIC OFFICER.

4426
03:14:38,558 --> 03:14:40,526
THE ISET -- CAN WE -- GREAT,

4427
03:14:40,526 --> 03:14:40,860
OKAY.

4428
03:14:40,860 --> 03:14:43,696
FOR THOSE WHO ARE NOT FAMILIAR,

4429
03:14:43,696 --> 03:14:47,733
ONE OF THE LEADING GLOBAL

4430
03:14:47,733 --> 03:14:49,502
ORGANIZATIONS LOOKING TO MAKE

4431
03:14:49,502 --> 03:14:53,439
CELL-BASED THERAPY A REALITY.

4432
03:14:53,439 --> 03:14:54,340
NEXT SLIDE.

4433
03:14:54,340 --> 03:14:59,812
AGAIN, TO GIVE A SMALL 

4434
03:14:59,812 --> 03:15:00,413
PERSPECTIVE, MULTI-THOUSAND

4435
03:15:00,413 --> 03:15:01,981
MEMBERS, GLOBALLY, WE FOCUS NOT

4436
03:15:01,981 --> 03:15:05,685
JUST ON SCIENCE BUT PARTICULARLY

4437
03:15:05,685 --> 03:15:07,320
ON REGULATORY COMMERCIALIZATION,

4438
03:15:07,320 --> 03:15:10,056
AND MANUFACTURING.

4439
03:15:10,056 --> 03:15:11,691
NEXT SLIDE.

4440
03:15:11,691 --> 03:15:13,092
AS SUCH HERE.

4441
03:15:13,092 --> 03:15:13,893
SO, NEXT SLIDE PLEASE.

4442
03:15:13,893 --> 03:15:15,728
WHAT I THOUGHT WOULD BE HELPFUL

4443
03:15:15,728 --> 03:15:17,997
WOULD BE A SWAT ANALYSIS

4444
03:15:17,997 --> 03:15:19,899
APPROACH, AND A LOT OF THE TOPIC

4445
03:15:19,899 --> 03:15:21,500
AREAS WE'VE TOUCHED ON, WHICH IS

4446
03:15:21,500 --> 03:15:22,969
IMPORTANT TO ME BECAUSE WE'RE

4447
03:15:22,969 --> 03:15:24,937
ALL THINKING THE SAME.

4448
03:15:24,937 --> 03:15:27,773
AND SO, IF YOU LOOK AT SECTOR

4449
03:15:27,773 --> 03:15:29,742
STRENGTHS, WHAT WE CAN LEARN,

4450
03:15:29,742 --> 03:15:35,748
THERE HAS BEEN TREMENDOUSLY

4451
03:15:35,748 --> 03:15:40,586
SUCCESSFUL CELL-BASED THERAPY, 

4452
03:15:40,586 --> 03:15:43,122
TRANSPLANTATION, CAR-T,

4453
03:15:43,122 --> 03:15:44,490
GENE-MODIFIED HEMATOPOIETIC STEM

4454
03:15:44,490 --> 03:15:45,691
CELLS.

4455
03:15:45,691 --> 03:15:49,962
WE'VE HEARD ABOUT iPSCs,

4456
03:15:49,962 --> 03:15:52,064
MSCs, GENE-MODIFIED, EDITED

4457
03:15:52,064 --> 03:15:54,700
IMMUNOREGULATORY CELLS, 

4458
03:15:54,700 --> 03:15:56,068
ENDOGENOUS TISSUE-SPECIFIC

4459
03:15:56,068 --> 03:15:57,336
PROGENITOR CELLS, EXOSOMES,

4460
03:15:57,336 --> 03:15:59,872
EXTRACELLULAR VESICLES IS,

4461
03:15:59,872 --> 03:16:00,940
THERE'S A STRONG PRE-CLINICAL

4462
03:16:00,940 --> 03:16:02,608
TRACK RECORD OF EFFICACY, BUT

4463
03:16:02,608 --> 03:16:05,111
ALSO IMPORTANTLY A GROWING

4464
03:16:05,111 --> 03:16:06,879
CLINICAL SAFETY RECORD.

4465
03:16:06,879 --> 03:16:07,780
GREAT, THANK YOU.

4466
03:16:07,780 --> 03:16:09,649
AND THE LIKE TOO.

4467
03:16:09,649 --> 03:16:13,786
SO, WHAT ARE THE WEAKNESSES,

4468
03:16:13,786 --> 03:16:14,020
RIGHT?

4469
03:16:14,020 --> 03:16:18,391
DESPITE MSC AS AN EXAMPLE, THERE

4470
03:16:18,391 --> 03:16:21,794
ARE THOUSANDS OF PRE-CLINICAL,

4471
03:16:21,794 --> 03:16:23,329
NON-CLINICAL STUDIES SHOWING YOU

4472
03:16:23,329 --> 03:16:26,365
CAN PICK YOUR DISEASE TARGET AND

4473
03:16:26,365 --> 03:16:27,566
ENDPOINTS, AND MSCs WILL SAVE

4474
03:16:27,566 --> 03:16:30,202
THE DAY.

4475
03:16:30,202 --> 03:16:31,737
BUT THEY JUST HAVEN'T WORKED

4476
03:16:31,737 --> 03:16:35,107
CLINICAL, YOU HAVE TO FIGURE OUT

4477
03:16:35,107 --> 03:16:36,509
WHY.

4478
03:16:36,509 --> 03:16:38,511
MULTIPLE UNRESOLVED ISSUES,

4479
03:16:38,511 --> 03:16:39,879
MANUFACTURING DOSE, DOSING, I

4480
03:16:39,879 --> 03:16:42,148
KEEP HARPING ON PATIENT

4481
03:16:42,148 --> 03:16:45,551
PHENOTYPE, NOT ONE SIZE FITS

4482
03:16:45,551 --> 03:16:46,285
ALL.

4483
03:16:46,285 --> 03:16:50,523
WE'VE TALKED ABOUT POTENCY OF

4484
03:16:50,523 --> 03:16:50,756
ACTION.

4485
03:16:50,756 --> 03:16:52,358
DELIVERY IS KEY, REGULATORY

4486
03:16:52,358 --> 03:16:54,226
HARMONIZATION, IT'S NOT JUST WE

4487
03:16:54,226 --> 03:16:55,895
THE INVESTIGATORS WHO DON'T

4488
03:16:55,895 --> 03:16:56,495
FULLY UNDERSTAND REGULATORY.

4489
03:16:56,495 --> 03:16:58,798
A LOT OF AGENCIES AND

4490
03:16:58,798 --> 03:17:00,032
INSTITUTIONS DON'T UNDERSTAND

4491
03:17:00,032 --> 03:17:01,934
THE REGULATORY AS WELL.

4492
03:17:01,934 --> 03:17:04,070
WORKFORCE, WE'LL TALK MORE ABOUT

4493
03:17:04,070 --> 03:17:04,270
AGAIN.

4494
03:17:04,270 --> 03:17:10,409
ALSO, IF YOU THINK ABOUT 

4495
03:17:10,409 --> 03:17:11,644
IMPLEMENTATION, REGIONAL

4496
03:17:11,644 --> 03:17:12,078
DISPARITIES, ACCESS,

4497
03:17:12,078 --> 03:17:12,678
IMPLEMENTATION, ET CETERA, AND

4498
03:17:12,678 --> 03:17:15,147
THE LIKE TOO.

4499
03:17:15,147 --> 03:17:16,449
WHAT ABOUT THREATS?

4500
03:17:16,449 --> 03:17:18,851
FUNDING IS A THREAT, AND THE

4501
03:17:18,851 --> 03:17:19,185
LIKE.

4502
03:17:19,185 --> 03:17:22,321
APPRECIATE THE TRACK RECORD OF

4503
03:17:22,321 --> 03:17:24,757
FUNDING, THE RMIP AND THINGS

4504
03:17:24,757 --> 03:17:32,098
LIKE THAT, BUT IT'S NEVER

4505
03:17:32,098 --> 03:17:32,832
ENOUGH, RIGHT?

4506
03:17:32,832 --> 03:17:34,467
I WANT TO HIGHLIGHT THAT WE'RE

4507
03:17:34,467 --> 03:17:37,103
ALL DEPENDENT ON THE ECONOMY, A

4508
03:17:37,103 --> 03:17:38,204
GOVERNMENT SHUTDOWN IS GOING TO

4509
03:17:38,204 --> 03:17:39,939
AFFECT HOW NIH IS GOING TO HAVE

4510
03:17:39,939 --> 03:17:41,607
MONEY TO SPEND, SO TO SPEAK.

4511
03:17:41,607 --> 03:17:43,342
I ALSO WANT TO SHIFT GEARS, IF

4512
03:17:43,342 --> 03:17:45,678
YOU THINK ABOUT WHERE ELSE DOES

4513
03:17:45,678 --> 03:17:49,915
MONEY COME FROM FOR THESE

4514
03:17:49,915 --> 03:17:52,918
THINGS?

4515
03:17:52,918 --> 03:17:55,488
FROM INDUSTRY, INVESTORS, AND

4516
03:17:55,488 --> 03:17:57,356
THERE'S A BURNOUT BECAUSE SO

4517
03:17:57,356 --> 03:17:59,658
MANY TRIALS ARE NOT WORKED.

4518
03:17:59,658 --> 03:18:01,727
WE'RE NOT MAKING MONEY ON THIS.

4519
03:18:01,727 --> 03:18:03,562
THE OTHER THING TOUCHED ON NOT

4520
03:18:03,562 --> 03:18:04,897
ENOUGH I THINK IS EDUCATION.

4521
03:18:04,897 --> 03:18:07,533
YOU SAY THE WORD STEM CELL, IT

4522
03:18:07,533 --> 03:18:11,070
EVOKES ALL TYPES OF MAGICAL

4523
03:18:11,070 --> 03:18:13,239
POLICIES AND WHATEVER.

4524
03:18:13,239 --> 03:18:15,941
AND STEM CELL MEDICAL TOURISM

4525
03:18:15,941 --> 03:18:17,043
INDUSTRY IS A REAL THREAT AND

4526
03:18:17,043 --> 03:18:19,412
STILL OUT THERE, AND THE LIKE.

4527
03:18:19,412 --> 03:18:21,347
WHAT KIND OF OPPORTUNITIES ARE

4528
03:18:21,347 --> 03:18:21,614
THERE?

4529
03:18:21,614 --> 03:18:24,417
WE'RE A CON SHORT YUM APPROACH

4530
03:18:24,417 --> 03:18:25,951
GLOBAL REACH, AND TO GO THROUGH

4531
03:18:25,951 --> 03:18:34,293
THE  THROUGH THE LAUNDRY LIST,

4532
03:18:34,293 --> 03:18:34,960
DEVELOPMENT, IMPLEMENTING,

4533
03:18:34,960 --> 03:18:35,594
MANUFACTURING IMPROVEMENTS, LOTS

4534
03:18:35,594 --> 03:18:39,665
OF WAYS TO DO THIS.

4535
03:18:39,665 --> 03:18:41,333
DELIVERY, I WANT TO HIGHLIGHT

4536
03:18:41,333 --> 03:18:43,135
ONE THING, SYSTEMIC NOT THE ONLY

4537
03:18:43,135 --> 03:18:43,569
WAY.

4538
03:18:43,569 --> 03:18:45,671
LOCAL DELIVERY, CAN YOU INJECT

4539
03:18:45,671 --> 03:18:46,972
OR ADMINISTER YOUR CELLS

4540
03:18:46,972 --> 03:18:50,176
SUBCUTANEOUSLY, FOR EXAMPLE, AND

4541
03:18:50,176 --> 03:18:52,044
THEY WILL HAVE DISTANT EFFECTS

4542
03:18:52,044 --> 03:18:54,113
THAT WILL AFFECT YOUR DISEASE OF

4543
03:18:54,113 --> 03:18:55,848
INTEREST OR DISEASE OF TARGET,

4544
03:18:55,848 --> 03:18:58,517
IF YOU WILL.

4545
03:18:58,517 --> 03:19:00,886
THIS IS NOT NECESSARILY LOCAL

4546
03:19:00,886 --> 03:19:03,522
INJECTION INTO A JOINT, BUT

4547
03:19:03,522 --> 03:19:05,925
INJECTION, AGAIN, SOMEWHERE ELSE

4548
03:19:05,925 --> 03:19:07,893
THAT WILL HAVE DISTANT EFFECTS.

4549
03:19:07,893 --> 03:19:10,396
HOW DOES THAT WORK?

4550
03:19:10,396 --> 03:19:12,531
YOU MODIFY IMMUNE AND

4551
03:19:12,531 --> 03:19:13,165
INFLAMMATORY PATHWAYS INVOLVED,

4552
03:19:13,165 --> 03:19:14,567
AND THEY HAVE SYSTEMIC EFFECTS,

4553
03:19:14,567 --> 03:19:16,235
IF YOU WILL.

4554
03:19:16,235 --> 03:19:19,939
WE HEARD LOCAL DELIVERY, HEARD

4555
03:19:19,939 --> 03:19:21,707
FINN TALK ABOUT CF.

4556
03:19:21,707 --> 03:19:22,708
TO GET THOSE CELLS ENGRAFTED

4557
03:19:22,708 --> 03:19:25,077
RIGHT NOW THEY HAVE TO USE

4558
03:19:25,077 --> 03:19:27,947
DETERGENT TO RIP OPEN HOLES IN

4559
03:19:27,947 --> 03:19:31,250
THE EPITHELIUM, THAT'S NOT A

4560
03:19:31,250 --> 03:19:36,489
CLINICAL STRATEGY, BETTER WAYS

4561
03:19:36,489 --> 03:19:38,891
TO GO.

4562
03:19:38,891 --> 03:19:41,827
LATE STAGE DEVELOPMENT,

4563
03:19:41,827 --> 03:19:43,462
COMMERCIALIZATION, RAPID

4564
03:19:43,462 --> 03:19:44,130
ANALYTICS ARE CRITICAL IN

4565
03:19:44,130 --> 03:19:46,465
QUALITY CONTROL FOR MASS

4566
03:19:46,465 --> 03:19:47,500
PRODUCTION.

4567
03:19:47,500 --> 03:19:48,501
REGISTRIES, SO MENTIONED

4568
03:19:48,501 --> 03:19:50,002
EARLIER, FOCUS ON PATIENT

4569
03:19:50,002 --> 03:19:51,770
SELECTION, POINT OF CARE PATIENT

4570
03:19:51,770 --> 03:19:55,074
ASSESSMENTS FOR ACUTE DISEASE

4571
03:19:55,074 --> 03:19:56,809
APPLICATIONS, GOES TO THE

4572
03:19:56,809 --> 03:19:57,776
BIOMARKERS.

4573
03:19:57,776 --> 03:19:59,912
RECENT TRIALS OF CELL-BASED

4574
03:19:59,912 --> 03:20:02,081
THERAPY FOR COVID, ACUTE

4575
03:20:02,081 --> 03:20:03,315
RESPIRATORY DISTRESS SYNDROME,

4576
03:20:03,315 --> 03:20:06,152
SOME TRIALS WORKED, SOME TRIALS

4577
03:20:06,152 --> 03:20:07,019
DIDN'T WORK.

4578
03:20:07,019 --> 03:20:08,954
HOW DO WE FERRET OUT WHO IS

4579
03:20:08,954 --> 03:20:10,256
GOING TO RESPOND?

4580
03:20:10,256 --> 03:20:12,358
IF WE COULD HAVE, FOR EXAMPLE, A

4581
03:20:12,358 --> 03:20:14,460
QUICK BLOOD TEST, FOUR OR FIVE

4582
03:20:14,460 --> 03:20:15,094
INFLAMMATORY MARKERS, YOU'RE

4583
03:20:15,094 --> 03:20:16,962
LIKELY TO RESPOND, YOU'RE LESS

4584
03:20:16,962 --> 03:20:19,298
LIKELY TO RESPOND, IT'S GOING TO

4585
03:20:19,298 --> 03:20:24,503
MAKE SUCCESS I THINK MORE

4586
03:20:24,503 --> 03:20:25,838
ACHIEVABLE.

4587
03:20:25,838 --> 03:20:26,906
PATIENT/CAREGIVER EDUCATION,

4588
03:20:26,906 --> 03:20:27,706
REGULATORY HARMONIZATION,

4589
03:20:27,706 --> 03:20:28,841
WORKFORCE DEVELOPMENT, TISSUE

4590
03:20:28,841 --> 03:20:32,077
ENGINEERING IN VARIOUS FORMS,

4591
03:20:32,077 --> 03:20:33,579
ORGANOID SCAFFOLD, HYDROGELS AND

4592
03:20:33,579 --> 03:20:34,480
THE LIKE.

4593
03:20:34,480 --> 03:20:35,481
THERE'S A HUGE OPPORTUNITY HERE

4594
03:20:35,481 --> 03:20:35,714
I THINK.

4595
03:20:35,714 --> 03:20:38,984
ALL RIGHT.

4596
03:20:38,984 --> 03:20:43,255
A COUPLE OF REPRESENTATIVE 

4597
03:20:43,255 --> 03:20:44,490
NEAR-TERM PROPOSED SOLUTIONS FOR

4598
03:20:44,490 --> 03:20:48,761
TO HELP AND LEAD SOME EFFORTS,

4599
03:20:48,761 --> 03:20:51,263
MANUFACTURING AND ANALYTICS

4600
03:20:51,263 --> 03:20:52,898
WORKFORCE DEVELOPMENT,

4601
03:20:52,898 --> 03:20:53,799
ACKNOWLEDGING THE ARMY, ARMI,

4602
03:20:53,799 --> 03:21:02,908
HAS DONE A LOT OF WORK, NSF, AS

4603
03:21:02,908 --> 03:21:05,611
WAS ARTICULATED.

4604
03:21:05,611 --> 03:21:07,513
TECHNOLOGY IS CRITICAL, SUCCESS

4605
03:21:07,513 --> 03:21:10,549
FACTOR, THE IDEA TO HAVE CENTRAL

4606
03:21:10,549 --> 03:21:11,684
AND DECENTRALIZED MANUFACTURING

4607
03:21:11,684 --> 03:21:20,626
WITH QUALITY CONTROL AND AGAIN 

4608
03:21:20,626 --> 03:21:21,727
ANALYTICS.

4609
03:21:21,727 --> 03:21:24,129
INDUSTRY IS A BROAD TERM,

4610
03:21:24,129 --> 03:21:24,663
INCORPORATING A.I.,

4611
03:21:24,663 --> 03:21:25,564
MACHINE-BASED LEARNING AND THE

4612
03:21:25,564 --> 03:21:27,633
LIKE.

4613
03:21:27,633 --> 03:21:29,301
ONE OF THE HURDLES IS EACH STEP

4614
03:21:29,301 --> 03:21:30,603
ALONG THE WAY, HAVING THE

4615
03:21:30,603 --> 03:21:31,837
QUALITY CONTROL SO YOUR PRODUCT

4616
03:21:31,837 --> 03:21:35,741
IS WHAT YOU WANT IT TO BE IN A

4617
03:21:35,741 --> 03:21:37,376
REPRODUCIBLE MANNER, IF YOU

4618
03:21:37,376 --> 03:21:37,810
WILL.

4619
03:21:37,810 --> 03:21:41,847
AGAIN, THINGS THAT WE'VE ALL

4620
03:21:41,847 --> 03:21:43,415
TALKED ABOUT, NOVEL

4621
03:21:43,415 --> 03:21:45,384
TECHNOLOGIES, CENTRAL QUALITY

4622
03:21:45,384 --> 03:21:46,986
ASSESSMENT, AUTOMATION, ET

4623
03:21:46,986 --> 03:21:47,820
CETERA.

4624
03:21:47,820 --> 03:21:49,321
EVOLUTION OF REGULATORY

4625
03:21:49,321 --> 03:21:49,822
STANDARDS AND PRACTICE,

4626
03:21:49,822 --> 03:21:52,625
EXPANSION OF THE ROLE OF

4627
03:21:52,625 --> 03:21:53,559
ACCREDITATION BODIES.

4628
03:21:53,559 --> 03:21:55,027
THERE'S NO -- IT'S LIKE THE WILD

4629
03:21:55,027 --> 03:21:57,129
WEST A LITTLE BIT OUT THERE IN

4630
03:21:57,129 --> 03:22:00,165
TERMS OF WHAT GETS APPROVED, WHO

4631
03:22:00,165 --> 03:22:02,468
DOES THE APPROVING.

4632
03:22:02,468 --> 03:22:03,902
SOME STANDPOINTS.

4633
03:22:03,902 --> 03:22:05,771
AND WE'RE THINKING BEYOND THE

4634
03:22:05,771 --> 03:22:08,507
U.S. BECAUSE AT SOME POINT THIS

4635
03:22:08,507 --> 03:22:13,879
WAS A GLOBAL THERAPY, AND SO

4636
03:22:13,879 --> 03:22:15,514
HARMONIZATION WITH EUA, EMA,

4637
03:22:15,514 --> 03:22:16,315
OTHER REGULATORY AGENCIES AROUND

4638
03:22:16,315 --> 03:22:18,050
THE WORLD IN WHICH WE WANT TO

4639
03:22:18,050 --> 03:22:23,055
CURE PATIENTS AS WELL AS IN THE

4640
03:22:23,055 --> 03:22:23,555
U.S.

4641
03:22:23,555 --> 03:22:24,156
AND MANUFACTURING AND

4642
03:22:24,156 --> 03:22:26,692
REGULATORY, ET CETERA.

4643
03:22:26,692 --> 03:22:27,893
ALL RIGHT.

4644
03:22:27,893 --> 03:22:29,728
OH, OKAY.

4645
03:22:29,728 --> 03:22:30,496
WORKFORCE DEVELOPMENT AND

4646
03:22:30,496 --> 03:22:32,197
TRAINING, I'M GLAD THIS CAME UP.

4647
03:22:32,197 --> 03:22:34,333
I'M GLAD YOU BROUGHT THIS UP

4648
03:22:34,333 --> 03:22:37,303
BECAUSE IT'S A HUGE ISSUE,

4649
03:22:37,303 --> 03:22:37,736
RIGHT?

4650
03:22:37,736 --> 03:22:40,172
AS AN ACADEMIC, I CAN'T FIND

4651
03:22:40,172 --> 03:22:45,344
PEOPLE, I CAN'T FIND LAB TECHS.

4652
03:22:45,344 --> 03:22:46,512
ROSEMARY'S POINT ABOUT THE

4653
03:22:46,512 --> 03:22:47,946
ASSEMBLY LINE IS AS CRITICALLY

4654
03:22:47,946 --> 03:22:49,148
IMPORTANT AS WHO IS DRIVING THE

4655
03:22:49,148 --> 03:22:51,317
BOAT, IF YOU WILL.

4656
03:22:51,317 --> 03:22:54,920
THIS IS WHERE LEARNING FROM THE

4657
03:22:54,920 --> 03:22:58,957
NSF, FROM ARMI, AND BEING ABLE

4658
03:22:58,957 --> 03:23:02,261
TO IMPLEMENT -- I DON'T KNOW IF

4659
03:23:02,261 --> 03:23:07,199
THERE'S A POINTER, BUT PRACTICE

4660
03:23:07,199 --> 03:23:09,368
PROGRAMS, SETTING STANDARDS FOR

4661
03:23:09,368 --> 03:23:12,771
FOCUSED TRAINING PROGRAMS,

4662
03:23:12,771 --> 03:23:13,339
HAVING WIDELY RECOGNIZED

4663
03:23:13,339 --> 03:23:15,574
ACCREDITATION SO THAT SOMEONE

4664
03:23:15,574 --> 03:23:16,842
WHO GOES THROUGH TRAINING

4665
03:23:16,842 --> 03:23:19,345
PROGRAMS SAYS HERE'S MY

4666
03:23:19,345 --> 03:23:20,179
CERTIFICATE, FOR EXAMPLE, NOT

4667
03:23:20,179 --> 03:23:21,313
NECESSARILY MY DEGREE BUT HERE

4668
03:23:21,313 --> 03:23:22,915
IS MY CERTIFICATE, I CAN DO WHAT

4669
03:23:22,915 --> 03:23:25,351
YOU WANT ME TO DO, GIVE ME A

4670
03:23:25,351 --> 03:23:26,452
GOOD JOB, A WIN-WIN SITUATION IF

4671
03:23:26,452 --> 03:23:27,853
WE CAN MAKE THIS WORK.

4672
03:23:27,853 --> 03:23:30,289
THERE ARE SOME OUT THERE, BUT TO

4673
03:23:30,289 --> 03:23:33,325
BROADEN THIS AND HAVE THE NIH

4674
03:23:33,325 --> 03:23:37,830
LEAD THE WAY IN SO MANY RESPECTS

4675
03:23:37,830 --> 03:23:40,099
CAN BE REALLY BENEFICIAL,

4676
03:23:40,099 --> 03:23:41,433
SOMETHING THE CONSORTIUM WITH

4677
03:23:41,433 --> 03:23:45,637
HELP, AN LONGITUDINAL TRAINING

4678
03:23:45,637 --> 03:23:46,805
FOR LONG-TERM DEVELOPMENT,

4679
03:23:46,805 --> 03:23:47,840
OBVIOUSLY.

4680
03:23:47,840 --> 03:23:51,643
MY LAST SIDE IS CELL SOURCE AND

4681
03:23:51,643 --> 03:23:52,311
QUALIFICATION.

4682
03:23:52,311 --> 03:23:56,448
I'VE NOT AN iPSC RESEARCHER

4683
03:23:56,448 --> 03:23:57,883
NECESSARILY BUT LISTENING TO

4684
03:23:57,883 --> 03:23:59,752
EVERYTHING GOING ON, IT'S THE

4685
03:23:59,752 --> 03:24:00,519
MANUFACTURING.

4686
03:24:00,519 --> 03:24:02,788
FIGURE OUT THE SCIENCE, IT'S NOT

4687
03:24:02,788 --> 03:24:03,655
ONE-SIZE-FITS-ALL, OF COURSE,

4688
03:24:03,655 --> 03:24:07,092
BUT WHO IS GOING TO, AGAIN, YOU

4689
03:24:07,092 --> 03:24:08,694
SAID -- MULTIPLE PEOPLE SAID

4690
03:24:08,694 --> 03:24:12,498
THIS, IF WE CAN WORK TO MAKE

4691
03:24:12,498 --> 03:24:16,168
THIS HAPPEN, THEN I THINK THIS

4692
03:24:16,168 --> 03:24:20,773
IS WHERE ISCT HAS THE

4693
03:24:20,773 --> 03:24:26,412
BACKGROUND, THIS IS A PEP TALK 

4694
03:24:26,412 --> 03:24:28,714
FOR ISCT, THE BACKGROUND

4695
03:24:28,714 --> 03:24:30,616
EXPERIENCE, EXPERTISE AND THE

4696
03:24:30,616 --> 03:24:32,351
LIKE TO SHAPE MOLDS AND LEAD THE

4697
03:24:32,351 --> 03:24:32,584
EFFORTS.

4698
03:24:32,584 --> 03:24:39,591
THANK YOU FOR THE OPPORTUNITY. 

4699
03:24:39,591 --> 03:24:42,561
>> UP NEXT WE HAVE TYLER
LAMB

4700
03:24:42,561 --> 03:24:53,071
AND ON DECK IS GRANT HOLLEY. 

4701
03:24:57,176 --> 03:24:58,210
>> GOOD AFTERNOON.

4702
03:24:58,210 --> 03:25:00,379
THANK YOU FOR THE INVITATION TO

4703
03:25:00,379 --> 03:25:01,713
PARTICIPATE IN THE WORKSHOP AND

4704
03:25:01,713 --> 03:25:03,248
OPPORTUNITY TO PRESENT.

4705
03:25:03,248 --> 03:25:04,883
I'M TYLER LAMB, DIRECTOR OF

4706
03:25:04,883 --> 03:25:06,218
POLICY FOR INTERNATIONAL SOCIETY

4707
03:25:06,218 --> 03:25:07,286
FOR STEM CELL RESEARCH.

4708
03:25:07,286 --> 03:25:09,555
I BELIEVE THIS IS THE FIRST

4709
03:25:09,555 --> 03:25:15,294
EVENT OF THE REGENERATIVE 

4710
03:25:15,294 --> 03:25:18,363
MEDICINE INNOVATION PROJECT THAT

4711
03:25:18,363 --> 03:25:22,401
ISTSR HAS PARTICIPATED.

4712
03:25:22,401 --> 03:25:24,703
THE IDEAS WERE DEVELOPED FOR THE

4713
03:25:24,703 --> 03:25:28,006
WORK OF THE MANUFACTURING

4714
03:25:28,006 --> 03:25:28,941
CLINICAL AND TRANSLATION

4715
03:25:28,941 --> 03:25:33,111
COMMITTEE AND SOME OTHER AREAS

4716
03:25:33,111 --> 03:25:36,048
WHERE ISSCR IS MOVING FROM BENCH

4717
03:25:36,048 --> 03:25:39,117
TO CLINIC.

4718
03:25:39,117 --> 03:25:41,019
GIVEN THE GOALS OF THE WORKSHOP

4719
03:25:41,019 --> 03:25:43,755
WE THINK IT'S PARALLEL IF NOT

4720
03:25:43,755 --> 03:25:45,457
CONGRUENT AND POTENTIALLY

4721
03:25:45,457 --> 03:25:45,791
USEFUL.

4722
03:25:45,791 --> 03:25:56,335
FIRST JUST A QUICK INTRODUCTION

4723
03:25:57,703 --> 03:26:04,209
OF ISSCR, WE'RE GLOBAL, IN 80 

4724
03:26:04,209 --> 03:26:06,044
COUNTRIES, COUNT 4700

4725
03:26:06,044 --> 03:26:08,080
SCIENTISTS, ETHICISTS AND

4726
03:26:08,080 --> 03:26:09,781
BUSINESS LEADERS, BEST KNOWN FOR

4727
03:26:09,781 --> 03:26:11,583
GUIDELINES, YOU MAY BE FAMILIAR.

4728
03:26:11,583 --> 03:26:13,619
WE HOST ONE OF THE LARGEST

4729
03:26:13,619 --> 03:26:14,586
GATHERINGS OF STEM CELL

4730
03:26:14,586 --> 03:26:15,988
RESEARCHERS IN THE WORLD, OUR

4731
03:26:15,988 --> 03:26:20,526
ANNUAL MEETING TAKING PLACE NEXT

4732
03:26:20,526 --> 03:26:27,399
JULY IN HAMBURG, GERMANY.

4733
03:26:27,399 --> 03:26:29,501
WE'RE GOING WITH THE FIELD AND

4734
03:26:29,501 --> 03:26:31,970
HAVE EXPANDED SCOPE TO INCLUDE

4735
03:26:31,970 --> 03:26:41,413
TRANSLATIONAL AND CLINICAL

4736
03:26:41,413 --> 03:26:42,514
OFFERINGS.

4737
03:26:42,514 --> 03:26:45,183
WE'RE FORTUNATE TO COUNT AS

4738
03:26:45,183 --> 03:26:46,385
MEMBERSHIP MANY PIONEERS

4739
03:26:46,385 --> 03:26:49,755
RESPONSIBLE FOR THE TRANSLATION 

4740
03:26:49,755 --> 03:26:51,290
OF STEM CELL THERAPIES.

4741
03:26:51,290 --> 03:26:54,459
I WANT TO BRIEFLY TALK ABOUT OUR

4742
03:26:54,459 --> 03:26:56,261
STANDARDS INITIATIVE.

4743
03:26:56,261 --> 03:26:58,430
EARLIER THIS YEAR WE PUBLISHED

4744
03:26:58,430 --> 03:27:01,366
STANDARDS, DEVELOPED OVER TWO

4745
03:27:01,366 --> 03:27:02,467
YEARS WITH INTERNATIONAL

4746
03:27:02,467 --> 03:27:04,002
COLLABORATION, THIS DOCUMENT

4747
03:27:04,002 --> 03:27:05,737
IDENTIFIES QUALITY STANDARDS AND

4748
03:27:05,737 --> 03:27:06,872
OUTLINES, CORE PRINCIPLES FOR

4749
03:27:06,872 --> 03:27:09,474
LABORATORY USE OF TISSUE AND

4750
03:27:09,474 --> 03:27:10,809
PLURIPOTENT STEM CELLS AND IN

4751
03:27:10,809 --> 03:27:13,078
VITRO MODEL SYSTEMS THAT RELY ON

4752
03:27:13,078 --> 03:27:14,179
THEM.

4753
03:27:14,179 --> 03:27:15,247
EMPHASIS WAS A CREATING

4754
03:27:15,247 --> 03:27:17,549
RECOMMENDATIONS THAT WHEN TAKEN

4755
03:27:17,549 --> 03:27:19,217
TOGETHER ESTABLISH MINIMUM

4756
03:27:19,217 --> 03:27:21,286
CHARACTERIZATION AND REPORTING

4757
03:27:21,286 --> 03:27:22,054
CRITERIA FOR SCIENTISTS,

4758
03:27:22,054 --> 03:27:23,055
STUDENTS, TECHNICIANS, BASIC

4759
03:27:23,055 --> 03:27:24,790
RESEARCH LABS WORKING WITH HUMAN

4760
03:27:24,790 --> 03:27:25,457
STEM CELLS.

4761
03:27:25,457 --> 03:27:27,125
YOU CAN SEE THE SCOPE OF THE

4762
03:27:27,125 --> 03:27:29,394
DOCUMENT THERE.

4763
03:27:29,394 --> 03:27:33,865
WE'VE ALSO INITIATED A PHASE TWO

4764
03:27:33,865 --> 03:27:35,500
OF THIS PROJECT.

4765
03:27:35,500 --> 03:27:37,936
PHASE TWO IS UNDERWAY, ADDRESSES

4766
03:27:37,936 --> 03:27:40,005
BEST PRACTICES FOR TRANSLATION

4767
03:27:40,005 --> 03:27:42,207
OF PSC-BASED THERAPIES,

4768
03:27:42,207 --> 03:27:43,875
SCHEDULED TO BE COMPLETED IN

4769
03:27:43,875 --> 03:27:44,242
2025.

4770
03:27:44,242 --> 03:27:45,477
THIS DOCUMENT WILL PROPOSE

4771
03:27:45,477 --> 03:27:47,913
STANDARDS TO STREAMLINE THE

4772
03:27:47,913 --> 03:27:49,815
PROCESS OF DEVELOPING

4773
03:27:49,815 --> 03:27:50,749
PLURIPOTENT CELL DERIVED

4774
03:27:50,749 --> 03:27:52,050
CELLULAR THERAPIES, AND YOU CAN

4775
03:27:52,050 --> 03:27:55,654
SEE THE FOCUS OF PHASE TWO

4776
03:27:55,654 --> 03:27:55,854
THERE.

4777
03:27:55,854 --> 03:27:59,591
SO TO ENABLE OUR MEMBERS TO MAKE

4778
03:27:59,591 --> 03:28:02,027
ROBUST PCS THERAPIES THAT MEET

4779
03:28:02,027 --> 03:28:03,996
CURRENT AND FORTHCOMING

4780
03:28:03,996 --> 03:28:06,164
STANDARDS AND ADHERE TO GUIDANCE

4781
03:28:06,164 --> 03:28:09,568
BY REGULATORS WE'VE BEEN WORKING

4782
03:28:09,568 --> 03:28:11,436
WITH COMMITTEES RESPONSIBLE FOR

4783
03:28:11,436 --> 03:28:12,638
RESEARCH AND DEVELOPED

4784
03:28:12,638 --> 03:28:13,972
PROGRAMMING AND TRAINING AND

4785
03:28:13,972 --> 03:28:15,340
REGULATORY STRATEGY TO ADDRESS

4786
03:28:15,340 --> 03:28:16,975
DIFFICULTIES IN THE DEVELOPMENT

4787
03:28:16,975 --> 03:28:19,177
OF PSC THERAPIES.

4788
03:28:19,177 --> 03:28:20,612
IT'S FROM THE DEVELOPMENT OF

4789
03:28:20,612 --> 03:28:22,280
THESE MATERIALS THAT WE'VE

4790
03:28:22,280 --> 03:28:23,582
IDENTIFIED PAIN POINTS WE THINK

4791
03:28:23,582 --> 03:28:25,350
WOULD BE OF INTEREST TO

4792
03:28:25,350 --> 03:28:27,919
GOVERNMENT AND INDUSTRY PARTNERS

4793
03:28:27,919 --> 03:28:31,690
AND WOULD IF SOLVED OR

4794
03:28:31,690 --> 03:28:32,691
MITIGATED, ADVANCE THE FIELD FOR

4795
03:28:32,691 --> 03:28:34,459
PATIENTS IN NEED.

4796
03:28:34,459 --> 03:28:36,495
WE HEARD SEVERAL OF THESE

4797
03:28:36,495 --> 03:28:39,598
SUGGESTIONS ALREADY.

4798
03:28:39,598 --> 03:28:44,403
THOSE  ARE SELECTING A CELL

4799
03:28:44,403 --> 03:28:45,270
LINE, AGUESSING GENETIC

4800
03:28:45,270 --> 03:28:50,976
STABILITY, UNDERSTANDING HOSE

4801
03:28:50,976 --> 03:28:51,810
IMMUNE RESPONSE.

4802
03:28:51,810 --> 03:28:55,881
SO IN THINKING ABOUT THE PROCESS

4803
03:28:55,881 --> 03:28:58,517
FOR DEVELOPING A CELL LINE,

4804
03:28:58,517 --> 03:28:59,951
SELECTING A LINE, ONE ISSUE

4805
03:28:59,951 --> 03:29:03,422
AFTER SELECTING A LINE THE MANY

4806
03:29:03,422 --> 03:29:04,456
STEPS, FOR EXAMPLE,

4807
03:29:04,456 --> 03:29:06,058
CHARACTERIZATION, TIME, MONEY,

4808
03:29:06,058 --> 03:29:09,795
LEVEL OF SPECIALIZED TECHNICAL 

4809
03:29:09,795 --> 03:29:10,762
EXPERTISE, SMALL LABS AND

4810
03:29:10,762 --> 03:29:11,997
COMPANIES FEEL THE ISSUES MOST,

4811
03:29:11,997 --> 03:29:13,699
ESPECIALLY TIME AND COST.

4812
03:29:13,699 --> 03:29:15,367
A SECOND ISSUE IS INTELLECTUAL

4813
03:29:15,367 --> 03:29:16,902
PROPERTY AND LICENSING.

4814
03:29:16,902 --> 03:29:20,605
CELL LINES ESPECIALLY THOSE

4815
03:29:20,605 --> 03:29:23,008
GENETICALLY MODIFIED DERIVED CAN

4816
03:29:23,008 --> 03:29:25,410
BE PATENTED, AND TO USE PATENTED

4817
03:29:25,410 --> 03:29:26,745
CELL LINES RESEARCHERS NEED TO

4818
03:29:26,745 --> 03:29:28,547
ENTER INTO LICENSING AGREEMENT

4819
03:29:28,547 --> 03:29:36,254
WAS PATENT HOLDERS, TRACKING

4820
03:29:36,254 --> 03:29:36,788
DOWN INFORMATION.

4821
03:29:36,788 --> 03:29:37,489
FEE, ROYALTIES, AND RESTRICTIONS

4822
03:29:37,489 --> 03:29:40,726
ON SALE OF PRODUCTS DERIVED CAN

4823
03:29:40,726 --> 03:29:41,793
BE CHALLENGING, EVEN NEGOTIATING

4824
03:29:41,793 --> 03:29:44,663
CAN BE EXPENSIVE AND TIME

4825
03:29:44,663 --> 03:29:45,997
CONSUMING, TYPICALLY REQUIRING

4826
03:29:45,997 --> 03:29:46,698
LEGAL EXPERTISE.

4827
03:29:46,698 --> 03:29:48,500
THUS WE THINK AN AREA WHERE THE

4828
03:29:48,500 --> 03:29:49,601
TIMES OF PARTNERSHIPS DESCRIBED

4829
03:29:49,601 --> 03:29:52,871
HERE COULD BE USEFUL IS IN

4830
03:29:52,871 --> 03:29:55,307
DEVELOPING A BANK OF PUBLICLY

4831
03:29:55,307 --> 03:29:56,608
AVAILABLE PSC LINES.

4832
03:29:56,608 --> 03:29:59,377
WE THINK EASIER ACCESS TO A

4833
03:29:59,377 --> 03:30:00,345
VARIETY AND DIVERSITY OF PSC

4834
03:30:00,345 --> 03:30:02,948
LINES WOULD STREAMLINE THE

4835
03:30:02,948 --> 03:30:06,017
PROCESS FOR DEVELOPING CELL

4836
03:30:06,017 --> 03:30:09,521
THERAPY LEADING TO LOWER COSTS,

4837
03:30:09,521 --> 03:30:10,956
ENSURE SAFETY AND GENETIC

4838
03:30:10,956 --> 03:30:13,158
STABILITY AND CONSISTENCY.

4839
03:30:13,158 --> 03:30:15,060
AND COULD NEGOTIATE A BROAD

4840
03:30:15,060 --> 03:30:15,894
LICENSING AGREEMENT TO PROVIDE

4841
03:30:15,894 --> 03:30:17,763
CELL LINES WITH FEWER

4842
03:30:17,763 --> 03:30:19,164
RESTRICTIONS TO FACILITATE MORE

4843
03:30:19,164 --> 03:30:21,700
OPEN RESEARCH AND DEVELOPMENT

4844
03:30:21,700 --> 03:30:22,567
ACTIVITIES, COULD ALSO

4845
03:30:22,567 --> 03:30:23,635
POTENTIALLY ADVISE ON

4846
03:30:23,635 --> 03:30:25,704
RESTRICTIONS TO CELL LINES

4847
03:30:25,704 --> 03:30:27,038
OFFERED BY PATENT HOLDERS.

4848
03:30:27,038 --> 03:30:31,076
IF CELL LINES FROM THE

4849
03:30:31,076 --> 03:30:32,544
REGULATORY PERSPECTIVE, IF THEY

4850
03:30:32,544 --> 03:30:34,045
HAVE BEEN APPROVED FOR USE IN

4851
03:30:34,045 --> 03:30:36,248
CLINICAL TRIALS THIS CAN REDUCE

4852
03:30:36,248 --> 03:30:39,618
TIME AND COST ASSOCIATED WITH

4853
03:30:39,618 --> 03:30:40,786
REGULATORY FILINGS.

4854
03:30:40,786 --> 03:30:44,456
THE NEXT ISSUE I WANT TO TALK

4855
03:30:44,456 --> 03:30:46,758
ABOUT ABOUT IS ASSESSING GENETIC

4856
03:30:46,758 --> 03:30:47,025
STABILITY.

4857
03:30:47,025 --> 03:30:48,527
INTERESTED TO HEAR WHAT OTHERS

4858
03:30:48,527 --> 03:30:51,897
HAVE TO SAY ABOUT HOW A.I. CAN

4859
03:30:51,897 --> 03:30:54,366
CONTRIBUTE TO THIS PROCESS.

4860
03:30:54,366 --> 03:30:59,337
BUT GENOMIC STABILITY AND CON 

4861
03:30:59,337 --> 03:31:01,406
CONTEXT REFERS TO VARIABILITY IN

4862
03:31:01,406 --> 03:31:03,909
A POPULATION OF PSCs AND

4863
03:31:03,909 --> 03:31:06,311
STABILITY REFERS TO HIGH

4864
03:31:06,311 --> 03:31:07,879
FREQUENCY OF MUTATIONS WITH

4865
03:31:07,879 --> 03:31:08,380
GENOME.

4866
03:31:08,380 --> 03:31:09,915
ENSURING GENETIC STABILITY OF

4867
03:31:09,915 --> 03:31:13,418
PSC LINE WHEN DEVELOPING A

4868
03:31:13,418 --> 03:31:16,388
THERAPEUTIC PRODUCT IS CRITICAL

4869
03:31:16,388 --> 03:31:17,355
AS INSTABILITY CAN AFFECT SAFETY

4870
03:31:17,355 --> 03:31:18,056
AND EFFICACY.

4871
03:31:18,056 --> 03:31:21,393
TO ENSURE A CELL LINE IS STABLE,

4872
03:31:21,393 --> 03:31:22,194
RIGOROUS SCREENING IS REQUIRED,

4873
03:31:22,194 --> 03:31:26,565
SOME WHOLE GENOME WHOLE EXOME

4874
03:31:26,565 --> 03:31:28,667
SEQUENCING AND YOU CAN SEE THE

4875
03:31:28,667 --> 03:31:30,402
DIFFERENT POINTS WHERE YOU MIGHT

4876
03:31:30,402 --> 03:31:32,470
DO GENOMICS ANALYSIS TO ENSURE

4877
03:31:32,470 --> 03:31:34,773
STABILITY OF CELL POPULATION.

4878
03:31:34,773 --> 03:31:36,508
ISSUE WE'VE MADE SIGNIFICANT

4879
03:31:36,508 --> 03:31:38,743
PROGRESS IN ABILITY TO DETECT

4880
03:31:38,743 --> 03:31:39,945
AND QUANTIFY MUTATIONS BUT

4881
03:31:39,945 --> 03:31:41,947
UNDERSTANDING OF CONSEQUENCES OF

4882
03:31:41,947 --> 03:31:44,883
MUTATIONS HASN'T KEPT PACE.

4883
03:31:44,883 --> 03:31:46,952
THE ONLY PURE POPULATION AS WE

4884
03:31:46,952 --> 03:31:49,888
KNOW HAPPENS EVERY TIME A CELL

4885
03:31:49,888 --> 03:31:52,190
DIVIDES, THERE'S A NEED TO

4886
03:31:52,190 --> 03:31:54,059
DEVELOP STANDARDIZED ASSAYS AND

4887
03:31:54,059 --> 03:31:55,694
REACH CONCLUSIONS ON WHICH

4888
03:31:55,694 --> 03:31:56,995
MUTATIONS ARE DOING SO COULD

4889
03:31:56,995 --> 03:31:58,763
POTENTIALLY LOWER FREQUENCY OF

4890
03:31:58,763 --> 03:32:00,298
TESTING, REDUCE COST, PROVIDE

4891
03:32:00,298 --> 03:32:02,167
GREATER CLARITY ON WHAT

4892
03:32:02,167 --> 03:32:03,468
REGULATORS ARE LOOKING FOR AND

4893
03:32:03,468 --> 03:32:07,405
CONSIDER AREAS OF CONCERN FROM

4894
03:32:07,405 --> 03:32:07,806
GENOMICS ANALYSIS.

4895
03:32:07,806 --> 03:32:11,243
LAST ISSUE I WANT TO DISCUSS IS

4896
03:32:11,243 --> 03:32:12,244
UNDERSTANDING HOST IMMUNE

4897
03:32:12,244 --> 03:32:13,745
RESPONSE, THE LAST PAIN POINT.

4898
03:32:13,745 --> 03:32:19,217
TO DEVELOP LARGE SCALE

4899
03:32:19,217 --> 03:32:19,751
COMMERCIALIZED THERAPIES,

4900
03:32:19,751 --> 03:32:23,154
SOLVING ISSUE OF IMMUNE

4901
03:32:23,154 --> 03:32:23,855
REJECTION IS CRITICAL.

4902
03:32:23,855 --> 03:32:28,426
IF CELLS ARE IDENTIFIED AS

4903
03:32:28,426 --> 03:32:31,596
FOREIGN, POTENTIALLY REJECTING

4904
03:32:31,596 --> 03:32:36,101
THERAPY, A FAILURE. 

4905
03:32:36,101 --> 03:32:38,403
ALLOGENEIC REQUIRES GENE EDITS

4906
03:32:38,403 --> 03:32:40,805
TO CREATE DONOR CELLS, PERHAPS

4907
03:32:40,805 --> 03:32:44,075
KILLER SAFETY SWITCHES, EDITS

4908
03:32:44,075 --> 03:32:45,010
INCLUDE POTENTIAL COMPLICATIONS

4909
03:32:45,010 --> 03:32:45,977
NORMALLY ASSOCIATED WITH GENE

4910
03:32:45,977 --> 03:32:48,880
EDITING TO HAVE LONG LASTING

4911
03:32:48,880 --> 03:32:52,083
EFFECTS, IT'S IMPORTANT CELLS

4912
03:32:52,083 --> 03:32:55,987
CAN COEXIST FOR EXTENDED PIECE 

4913
03:32:55,987 --> 03:33:01,826
OF TIME, THE DURABILITY PIECE.

4914
03:33:01,826 --> 03:33:07,098
A LACK OF WIDELY ACCEPTED AND

4915
03:33:07,098 --> 03:33:08,934
STANDARDIZED ASSAYS OR BETTER

4916
03:33:08,934 --> 03:33:10,135
PREDICTIVE VALUE, LEARNING ABOUT

4917
03:33:10,135 --> 03:33:12,437
COMPLEXITY OF IMMUNE SYSTEM AND

4918
03:33:12,437 --> 03:33:13,605
VARIABILITY BETWEEN PATIENTS

4919
03:33:13,605 --> 03:33:15,407
COULD BE USEFUL, SOLVING THESE

4920
03:33:15,407 --> 03:33:17,676
CHALLENGES WOULD ACCELERATE AND

4921
03:33:17,676 --> 03:33:19,277
DE-RISK DEVELOPMENT OF

4922
03:33:19,277 --> 03:33:20,445
CELL-BASED THERAPIES.

4923
03:33:20,445 --> 03:33:24,516
THANK YOU.

4924
03:33:24,516 --> 03:33:26,885
 

4925
03:33:26,885 --> 03:33:32,524
>> THANK YOU VERY MUCH.

4926
03:33:32,524 --> 03:33:37,095
THIRD SPEAKER IS GRANT HOLLEY,

4927
03:33:37,095 --> 03:33:39,864
ON DECK IS MIKE DURAN.

4928
03:33:39,864 --> 03:33:43,001
>> LET'S SEE IF I CAN MESS
THIS

4929
03:33:43,001 --> 03:33:45,503
UP.

4930
03:33:45,503 --> 03:33:46,905
THERE WE GO.

4931
03:33:46,905 --> 03:33:49,908
I MADE NOTES.

4932
03:33:49,908 --> 03:33:51,543
PRESENTATION I PUT TOGETHER,

4933
03:33:51,543 --> 03:33:52,510
GREATLY ENJOYED DISCUSSION THIS

4934
03:33:52,510 --> 03:33:53,845
MORNING AND MAY CHANGE A COUPLE

4935
03:33:53,845 --> 03:33:55,480
THINGS TO HIT ON A FEW POINTS

4936
03:33:55,480 --> 03:33:57,582
THAT I FEEL REALLY NEED TO BE

4937
03:33:57,582 --> 03:33:58,216
HIT UPON.

4938
03:33:58,216 --> 03:34:00,852
I'LL TAKE IT FROM A DIFFERENT

4939
03:34:00,852 --> 03:34:02,053
PERSPECTIVE THAN MY PEERS, BUT

4940
03:34:02,053 --> 03:34:04,022
HOPEFULLY IN A WAY THAT'S GOING

4941
03:34:04,022 --> 03:34:05,890
TO HELP BUILD CONSORTIA MOVING

4942
03:34:05,890 --> 03:34:06,291
FORWARD.

4943
03:34:06,291 --> 03:34:07,659
WE'RE THE AMERICAN SOCIETY OF

4944
03:34:07,659 --> 03:34:11,162
GENE AND CELL THERAPY.

4945
03:34:11,162 --> 03:34:13,531
WE HAVE 6259 MEMBERS, WE'RE IN

4946
03:34:13,531 --> 03:34:15,633
THE MIDST OF RENEWALS RIGHT NOW,

4947
03:34:15,633 --> 03:34:18,136
IF YOU'RE OUT THERE PLEASE RENEW

4948
03:34:18,136 --> 03:34:19,971
YOUR MEMBERSHIP, JUST IN CASE OR

4949
03:34:19,971 --> 03:34:21,339
CEO IS TUNING IN, GOT TO SAY

4950
03:34:21,339 --> 03:34:22,307
THOSE THINGS.

4951
03:34:22,307 --> 03:34:24,142
WE HAVE A RELATIVELY YOUNG

4952
03:34:24,142 --> 03:34:25,810
MEMBERSHIP STARTING THIS YEAR

4953
03:34:25,810 --> 03:34:27,812
WITH 30 TO 39 BASE OUR AVERAGE,

4954
03:34:27,812 --> 03:34:29,714
WHICH IS YOUNG.

4955
03:34:29,714 --> 03:34:32,250
WHEN I FIRST CAME TO ASGCT THREE

4956
03:34:32,250 --> 03:34:34,352
YEARS AGO AVERAGE AGE WAS CLOSER

4957
03:34:34,352 --> 03:34:35,887
TO 55.

4958
03:34:35,887 --> 03:34:37,522
THERE'S NOTHING WRONG WITH 55.

4959
03:34:37,522 --> 03:34:39,924
BUT I'M LOOKING FOR RETIREMENT,

4960
03:34:39,924 --> 03:34:44,095
AND I WANT THESE YOUNG KIDS IN

4961
03:34:44,095 --> 03:34:45,797
BECAUSE THEY WILL KEEP THE

4962
03:34:45,797 --> 03:34:46,564
SOCIETY MOVING.

4963
03:34:46,564 --> 03:34:48,233
AT THE SAME TIME THEY ARE THE

4964
03:34:48,233 --> 03:34:49,801
ONES THAT ARE THE NEXT FACE AS

4965
03:34:49,801 --> 03:34:51,202
TO WHAT EVERYBODY IS DOING, AND

4966
03:34:51,202 --> 03:34:53,638
WE WANT TO MAKE SURE THESE

4967
03:34:53,638 --> 03:34:57,008
CONVERSATIONS ARE INCLUDING THEM

4968
03:34:57,008 --> 03:34:59,544
SO WE MADE A LOT OF EFFORT TO

4969
03:34:59,544 --> 03:35:00,745
BRING IN YOUNGER RESEARCHERS IN

4970
03:35:00,745 --> 03:35:04,349
HOPES OF BEING ABLE TO HAVE

4971
03:35:04,349 --> 03:35:05,283
THESE UNSILOED CONVERSATIONS,

4972
03:35:05,283 --> 03:35:07,252
THAT'S GOING TO BE A THEME.

4973
03:35:07,252 --> 03:35:08,753
SO OUR ANNUAL MEETING IN MAY, WE

4974
03:35:08,753 --> 03:35:11,790
ARE LOOKING TO BE ABLE TO

4975
03:35:11,790 --> 03:35:14,225
ATTRACT -- OH, IN MAY WE HAD --

4976
03:35:14,225 --> 03:35:15,527
I WAS LOOKING AT 8,000.

4977
03:35:15,527 --> 03:35:17,262
WE DID HAVE 8,000 PEOPLE AT OUR

4978
03:35:17,262 --> 03:35:18,596
ANNUAL MEETING, THE LARGEST

4979
03:35:18,596 --> 03:35:21,332
GROUPING OF CELL AND GENE

4980
03:35:21,332 --> 03:35:22,233
BIOLOGISTS IN THE WORLD.

4981
03:35:22,233 --> 03:35:24,502
BALTIMORE IS GOING TO BE COMING

4982
03:35:24,502 --> 03:35:26,671
UP IN 2024, GET YOUR HOTEL ROOM

4983
03:35:26,671 --> 03:35:28,239
NOW BECAUSE THERE'S GOING TO BE

4984
03:35:28,239 --> 03:35:30,208
WELL OVER 9,000 PEOPLE AT THIS

4985
03:35:30,208 --> 03:35:30,608
MEETING.

4986
03:35:30,608 --> 03:35:32,277
IT'S GOING TO BE A BIG ONE.

4987
03:35:32,277 --> 03:35:37,549
THESE ARE ALL IMPORTANT FACTORS,

4988
03:35:37,549 --> 03:35:40,518
NOT JUST COMMERCIALS.

4989
03:35:40,518 --> 03:35:42,720
BECAUSE WE JOINED THE BGTC IN

4990
03:35:42,720 --> 03:35:43,888
OCTOBER OF 2021, WE'RE VERY

4991
03:35:43,888 --> 03:35:46,324
HAPPY THAT WE DID.

4992
03:35:46,324 --> 03:35:47,859
WE LOVE THIS PARTNERSHIP.

4993
03:35:47,859 --> 03:35:50,795
WHAT WE DO WITHIN OUR ANNUAL

4994
03:35:50,795 --> 03:35:52,197
MEETING THAT ATTRACTS 9,000

4995
03:35:52,197 --> 03:35:55,066
PEOPLE NEXT YEAR IS THAT WE HOST

4996
03:35:55,066 --> 03:35:56,801
BGTC'S ANNUAL MEETING AS WELL.

4997
03:35:56,801 --> 03:35:58,069
ONE THING I KEPT HEARING

4998
03:35:58,069 --> 03:35:59,437
THROUGHOUT THIS MORNING IS YOU

4999
03:35:59,437 --> 03:36:01,639
NEED A VENUE, A PLACE WHERE YOU

5000
03:36:01,639 --> 03:36:08,980
CAN ALL COME TOGETHER AND TALK.

5001
03:36:08,980 --> 03:36:12,917
THAT'S WHAT ASGCT IS, A

5002
03:36:12,917 --> 03:36:13,585
COMMUNITY OF 55-YEAR-OLDS,

5003
03:36:13,585 --> 03:36:14,519
35-YEAR-OLD, DOESN'T MATTER

5004
03:36:14,519 --> 03:36:15,987
WHERE THEY COME FROM, THIS IS A

5005
03:36:15,987 --> 03:36:17,222
PLACE EVERYBODY COMES TOGETHER

5006
03:36:17,222 --> 03:36:20,592
TO BE ABLE TO DISCUSS GENE AND

5007
03:36:20,592 --> 03:36:21,459
CELL THERAPY.

5008
03:36:21,459 --> 03:36:23,428
YOU NEED THAT FOR YOUR UPCOMING

5009
03:36:23,428 --> 03:36:25,063
CONSORTIUM AS WELL.

5010
03:36:25,063 --> 03:36:26,598
YOU'RE GOING TO NEED IT A MEMBER

5011
03:36:26,598 --> 03:36:28,266
THAT'S ABLE TO HOST YOUR ANNUAL

5012
03:36:28,266 --> 03:36:30,335
MEETING AND IN SUCH A WAY YOU

5013
03:36:30,335 --> 03:36:31,836
CAN BRING THE ENTIRE COMMUNITY

5014
03:36:31,836 --> 03:36:33,304
TOGETHER TO HAVE THE

5015
03:36:33,304 --> 03:36:34,372
CONVERSATIONS THAT HAVE HAPPENED

5016
03:36:34,372 --> 03:36:34,739
THIS MORNING.

5017
03:36:34,739 --> 03:36:36,574
I DON'T KNOW IF IT'S JUST ME BUT

5018
03:36:36,574 --> 03:36:38,443
I FEEL THERE HAVE BEEN A NUMBER

5019
03:36:38,443 --> 03:36:39,878
OF CONVERSATIONS THIS MORNING

5020
03:36:39,878 --> 03:36:42,881
THAT YOU HAVE BEEN DYING TO

5021
03:36:42,881 --> 03:36:43,248
HAVE.

5022
03:36:43,248 --> 03:36:45,016
YOU NEED A VENUE FOR THIS TO BE

5023
03:36:45,016 --> 03:36:45,884
ABLE TO HAPPEN.

5024
03:36:45,884 --> 03:36:46,885
THIS IS MY NOTES.

5025
03:36:46,885 --> 03:36:51,356
I WAS GOING TO SAY THAT BUT I

5026
03:36:51,356 --> 03:36:52,891
HAVE THE WORD "STRONGER" AT THE

5027
03:36:52,891 --> 03:36:55,160
TOP TO DRILL THAT POINT HOME.

5028
03:36:55,160 --> 03:36:58,463
YEAH, THAT'S EVERYTHING WE DO.

5029
03:36:58,463 --> 03:36:59,697
THE KEY HERE, YOU NEED A VENUE.

5030
03:36:59,697 --> 03:37:04,135
WE LOVE WHAT WE'RE DOING WITH

5031
03:37:04,135 --> 03:37:04,602
THESE GUYS.

5032
03:37:04,602 --> 03:37:07,972
SO, WHAT I WAS SUPPOSED TO DO

5033
03:37:07,972 --> 03:37:09,307
WITH THIS WHOLE PIECE WAS GOING

5034
03:37:09,307 --> 03:37:11,309
TO OUR MEMBERS AND ASK WHAT ARE

5035
03:37:11,309 --> 03:37:12,243
YOUR RESPONSES, WHAT DO YOU WANT

5036
03:37:12,243 --> 03:37:13,111
US TO TAKE BACK?

5037
03:37:13,111 --> 03:37:16,414
WE GOT A FEW OF THOSE.

5038
03:37:16,414 --> 03:37:17,949
MY SECOND STRONGER POINT.

5039
03:37:17,949 --> 03:37:20,518
BUT THE FIRST ONE IS WHEN

5040
03:37:20,518 --> 03:37:21,553
APPLYING FOR NIH FUNDING

5041
03:37:21,553 --> 03:37:24,622
SUCCESSFUL PROGRAMS SEEM TO BE

5042
03:37:24,622 --> 03:37:27,225
HEAVILY WEIGHTED TO MECHANISTIC

5043
03:37:27,225 --> 03:37:27,992
HYPOTHESIS THEN DRIVEN STUDYING,

5044
03:37:27,992 --> 03:37:29,427
CHALLENGING FOR PEOPLE WHO WANT

5045
03:37:29,427 --> 03:37:30,395
TO DEVELOP NEW THERAPEUTICS TO

5046
03:37:30,395 --> 03:37:31,162
BE FUNDED.

5047
03:37:31,162 --> 03:37:32,297
THIS WASN'T JUST ONE RESPONSE.

5048
03:37:32,297 --> 03:37:33,898
WHEN I WANTED TO KNOW WHAT IT IS

5049
03:37:33,898 --> 03:37:37,302
THAT I SHOULD SAY UP HERE

5050
03:37:37,302 --> 03:37:40,705
REPRESENTING ASGCT I WENT TO 45

5051
03:37:40,705 --> 03:37:42,340
MEMBERS, 45 MEMBERS ALL SAID

5052
03:37:42,340 --> 03:37:44,842
SOMETHING TO THIS LINE.

5053
03:37:44,842 --> 03:37:47,011
IT WAS PRETTY FAR DOWN THE LINE.

5054
03:37:47,011 --> 03:37:48,846
THIS IS A VERY STRONG STATEMENT.

5055
03:37:48,846 --> 03:37:57,956
THIS IS HOW I GET THE DATA FOR

5056
03:37:57,956 --> 03:37:58,623
ASGCT.

5057
03:37:58,623 --> 03:38:00,525
I'LL STAY STRONGLY, IT DOESN'T

5058
03:38:00,525 --> 03:38:03,661
JUST COME FROM 27 YEARS OF BEING

5059
03:38:03,661 --> 03:38:05,096
A SCIENCE EDUCATOR, JUST DOESN'T

5060
03:38:05,096 --> 03:38:10,235
COME FROM ASGCT.

5061
03:38:10,235 --> 03:38:12,003
THIS IS COMING FROM HUNDREDS OF

5062
03:38:12,003 --> 03:38:13,838
SURVEYS, IN OUR SOCIETY OR NOT.

5063
03:38:13,838 --> 03:38:14,939
BETTER EDUCATIONAL PROGRAMMING

5064
03:38:14,939 --> 03:38:17,242
IS NEEDED AT PARTICIPANT LEVEL

5065
03:38:17,242 --> 03:38:20,111
SO CLINICIANS, PATIENTS, YOU CAN

5066
03:38:20,111 --> 03:38:24,382
READ, TO HIT ON THIS PIECE 

5067
03:38:24,382 --> 03:38:24,649
STRONGER.

5068
03:38:24,649 --> 03:38:26,217
I WAS GOING TO USE THE

5069
03:38:26,217 --> 03:38:28,486
MICROPHONE BEFORE AS WELL.

5070
03:38:28,486 --> 03:38:30,722
YOU'VE BEEN SAYING WE NEED

5071
03:38:30,722 --> 03:38:31,422
EDUCATIONAL PROGRAM FOG

5072
03:38:31,422 --> 03:38:32,056
MANUFACTURING FOLKS, YOU'RE

5073
03:38:32,056 --> 03:38:32,490
ABSOLUTELY RIGHT.

5074
03:38:32,490 --> 03:38:34,025
THOSE THAT SAID WE NEED

5075
03:38:34,025 --> 03:38:35,893
EDUCATION PROGRAM FOR CLINICAL

5076
03:38:35,893 --> 03:38:37,295
FOLKS, YOU'RE ABSOLUTELY RIGHT.

5077
03:38:37,295 --> 03:38:39,931
THOSE THAT SAID WE NEED

5078
03:38:39,931 --> 03:38:41,266
EDUCATION PROGRAM BETWEEN US,

5079
03:38:41,266 --> 03:38:43,001
BECAUSE WE'RE SOMETIMES IN

5080
03:38:43,001 --> 03:38:44,302
DIFFERENT SILOS, GUESS WHAT,

5081
03:38:44,302 --> 03:38:45,603
YOU'RE ABSOLUTELY RIGHT.

5082
03:38:45,603 --> 03:38:47,605
IT DOESN'T MATTER THE

5083
03:38:47,605 --> 03:38:48,439
DEMOGRAPHIC.

5084
03:38:48,439 --> 03:38:50,541
DOES MATTER WHERE YOU ARE WITHIN

5085
03:38:50,541 --> 03:38:54,045
THE COMMUNITY.

5086
03:38:54,045 --> 03:38:56,914
THERE ARE LARGE EDUCATIONAL

5087
03:38:56,914 --> 03:39:00,084
POTHOLES, IF YOU WILL, THAT ARE

5088
03:39:00,084 --> 03:39:01,052
NOT PRESENT.

5089
03:39:01,052 --> 03:39:02,387
NOBODY DID IT ON PURPOSE.

5090
03:39:02,387 --> 03:39:05,023
THIS IS JUST MOVING SO

5091
03:39:05,023 --> 03:39:06,057
INCREDIBLY FAST.

5092
03:39:06,057 --> 03:39:08,660
BOAST CELL AND GENE THERAPIES

5093
03:39:08,660 --> 03:39:10,795
ARE MOVING SO INCREDIBLY QUICKLY

5094
03:39:10,795 --> 03:39:12,864
MOST FOLKS ARE PLAYING CATCH-UP,

5095
03:39:12,864 --> 03:39:15,867
AND YOU CAN'T EVEN GET CAUGHT UP

5096
03:39:15,867 --> 03:39:17,969
BECAUSE IT KEEPS MOVING SO

5097
03:39:17,969 --> 03:39:19,370
QUICKLY.

5098
03:39:19,370 --> 03:39:20,138
AS LONG AS EDUCATION PROGRAM,

5099
03:39:20,138 --> 03:39:21,906
ALONG WITH WHAT YOU'RE DOING,

5100
03:39:21,906 --> 03:39:23,508
DOESN'T MATTER THE DEMOGRAPHIC,

5101
03:39:23,508 --> 03:39:25,009
IS GOING TO BE AD HOC, WE'RE

5102
03:39:25,009 --> 03:39:27,312
NEVER GOING TO BE IN THE SAME

5103
03:39:27,312 --> 03:39:27,512
PLACE.

5104
03:39:27,512 --> 03:39:29,547
WHEN YOU'RE STARTING TO BE ABLE

5105
03:39:29,547 --> 03:39:31,282
TO LOOK AT PROGRAMS, STARTING TO

5106
03:39:31,282 --> 03:39:33,017
LOOK WITHIN A CONSORTIUM, BEING

5107
03:39:33,017 --> 03:39:35,853
ABLE TO EVEN LOOK AT A

5108
03:39:35,853 --> 03:39:36,454
THERAPEUTIC PRODUCTION,

5109
03:39:36,454 --> 03:39:37,288
EDUCATION HAS TO BE ONE OF THE

5110
03:39:37,288 --> 03:39:40,024
FIRST THINGS THAT YOU THINK OF.

5111
03:39:40,024 --> 03:39:42,860
TRYING TO DO THIS IN ARREARS IS

5112
03:39:42,860 --> 03:39:45,163
GOING TO CAUSE A HARSH LESSON, A

5113
03:39:45,163 --> 03:39:48,266
LESSON THAT GENE THERAPY IS

5114
03:39:48,266 --> 03:39:48,800
LEARNING QUICKLY TODAY.

5115
03:39:48,800 --> 03:39:50,535
IF YOU WANT MY THOUGHTS ON THAT,

5116
03:39:50,535 --> 03:39:51,402
WE'LL TALK LATER.

5117
03:39:51,402 --> 03:39:53,171
BUT NIH WILL BE IN A GREAT

5118
03:39:53,171 --> 03:39:55,239
POSITION TO BE ABLE TO DO THIS.

5119
03:39:55,239 --> 03:39:58,643
NIH'S NAME IS A TRUSTED NAME

5120
03:39:58,643 --> 03:40:00,144
AMONGST RESEARCHERS, CLINICIANS,

5121
03:40:00,144 --> 03:40:02,780
THE PUBLIC, PATIENTS, DOESN'T

5122
03:40:02,780 --> 03:40:04,115
MATTER WHO.

5123
03:40:04,115 --> 03:40:06,084
AND THIS CONSORTIUM CAN SET UP

5124
03:40:06,084 --> 03:40:07,919
THAT LEVEL OF PROGRAMMING TO BE

5125
03:40:07,919 --> 03:40:11,522
ABLE TO HELP US ALL GET ON THE

5126
03:40:11,522 --> 03:40:12,690
SAME PAGE, REDUCE THE SILOS,

5127
03:40:12,690 --> 03:40:14,592
SAME THINGS WE'VE BEEN HEARING

5128
03:40:14,592 --> 03:40:15,393
HERE TODAY.

5129
03:40:15,393 --> 03:40:18,129
ALL EDUCATION IS IS JUST

5130
03:40:18,129 --> 03:40:18,963
SPECIALIZED COMMUNICATION.

5131
03:40:18,963 --> 03:40:20,732
IT SOUNDS LIKE THAT'S WHAT THIS

5132
03:40:20,732 --> 03:40:21,699
CONSORTIUM CAN PROVIDE.

5133
03:40:21,699 --> 03:40:27,672
THANK YOU GUYS VERY MUCH.

5134
03:40:27,672 --> 03:40:29,807
 

5135
03:40:29,807 --> 03:40:34,312
>> NEXT SPEAKER IS MIKE
DORAN.

5136
03:40:34,312 --> 03:40:44,756
ON DECK IS MARINA MADRID. 

5137
03:40:45,790 --> 03:40:48,159
>> SO I DO PLAN TO ATTEND
YOUR

5138
03:40:48,159 --> 03:40:50,561
MEETING IN BALTIMORE NEXT YEAR.

5139
03:40:50,561 --> 03:40:52,597
I LOOK FORWARD TO THAT.

5140
03:40:52,597 --> 03:40:56,534
>> [OFF MICROPHONE].

5141
03:40:56,534 --> 03:40:58,202
>> PROBABLY ALREADY.

5142
03:40:58,202 --> 03:41:04,142
I'M MIKE  DORAN, I WAS AN

5143
03:41:04,142 --> 03:41:05,743
ACADEMIC IN AUSTRALIA,

5144
03:41:05,743 --> 03:41:07,178
INTERESTED IN STEM CELLS,

5145
03:41:07,178 --> 03:41:10,681
PRIMARILY CARTILAGE, I KNOW 

5146
03:41:10,681 --> 03:41:14,051
SOME OF YOU IN THE AUDIENCE.

5147
03:41:14,051 --> 03:41:23,060
I'M A DIRECTOR OF CELL THERAPY

5148
03:41:23,060 --> 03:41:24,495
AT ASTRAZENECA.

5149
03:41:24,495 --> 03:41:27,832
I THOUGHT I WOULD COMMENT

5150
03:41:27,832 --> 03:41:29,167
GENERICALLY, AT ASTRAZENECA THE

5151
03:41:29,167 --> 03:41:30,735
WAY OF PRODUCT DEVELOPMENT

5152
03:41:30,735 --> 03:41:34,138
WORKS, WE HAVE R&D
DEPARTMENTS

5153
03:41:34,138 --> 03:41:35,440
AND, FOR EXAMPLE, IN R&D

5154
03:41:35,440 --> 03:41:37,542
DEPARTMENT I'M PART OF WE MIGHT

5155
03:41:37,542 --> 03:41:39,177
BE WORKING WITH ANY NUMBER OF

5156
03:41:39,177 --> 03:41:42,180
CELLS, WE WILL USE QUITE OFTEN

5157
03:41:42,180 --> 03:41:44,916
LENTIVIRUS AS JUST THE MOST

5158
03:41:44,916 --> 03:41:50,688
EFFICIENT TOOL TO EXPRESS

5159
03:41:50,688 --> 03:41:51,756
TRANSGENE.

5160
03:41:51,756 --> 03:41:53,991
BUT THE BIOPROCESS DEPARTMENT IS

5161
03:41:53,991 --> 03:41:56,727
R&D CONCEPTS, TRANSLATED
INTO

5162
03:41:56,727 --> 03:41:57,128
SOMETHING.

5163
03:41:57,128 --> 03:41:59,697
SO R&D DEPARTMENT WOULD TAKE
OUR

5164
03:41:59,697 --> 03:42:00,965
OPTIMIZED TRANSGENE AND THEY

5165
03:42:00,965 --> 03:42:03,734
WOULD INSERT IT INTO THE CELL,

5166
03:42:03,734 --> 03:42:06,270
IF IT WERE A PLURIPOTENT CELL

5167
03:42:06,270 --> 03:42:08,005
USING PROBABLY A SINGLE OR

5168
03:42:08,005 --> 03:42:10,741
DOUBLE STRAND DNA TEMPLATE AND

5169
03:42:10,741 --> 03:42:12,810
CRISPR, RIGHT?

5170
03:42:12,810 --> 03:42:15,213
SO ALL I'M SAYING IS THAT WE

5171
03:42:15,213 --> 03:42:16,514
DON'T HAVE TO ASSIGN THIS, YOU

5172
03:42:16,514 --> 03:42:18,816
DON'T HAVE TO DO EVERYTHING,

5173
03:42:18,816 --> 03:42:19,517
BECAUSE YOU HAVE DIFFERENT

5174
03:42:19,517 --> 03:42:21,686
DEPARTMENTS THAT ARE PROBABLY

5175
03:42:21,686 --> 03:42:23,387
GOING TO PICK UP THE CLINICAL

5176
03:42:23,387 --> 03:42:25,256
TRANSLATION STEPS, AND MAKE SURE

5177
03:42:25,256 --> 03:42:29,227
THAT IT'S ALL DONE IN THE SAFEST

5178
03:42:29,227 --> 03:42:31,629
MANNER THAT MEETS ALL THE

5179
03:42:31,629 --> 03:42:33,164
REGULATORY REQUIREMENTS.

5180
03:42:33,164 --> 03:42:35,466
SO WHEN I THOUGHT WHAT CAN I SAY

5181
03:42:35,466 --> 03:42:39,637
HERE THAT I'M ALLOWED  TO SAY,

5182
03:42:39,637 --> 03:42:40,838
I'LL SAY SOMETHING UNIQUE.

5183
03:42:40,838 --> 03:42:42,306
I HOPE IT'S UNIQUE.

5184
03:42:42,306 --> 03:42:44,575
I THOUGHT, MAYBE THE FIELD OF

5185
03:42:44,575 --> 03:42:45,776
REGENERATIVE MEDICINE IS BETTER

5186
03:42:45,776 --> 03:42:47,612
OFF INTERVENING EARLY.

5187
03:42:47,612 --> 03:42:49,747
MAYBE WE SHOULDN'T BE THINKING

5188
03:42:49,747 --> 03:42:51,549
OF LAST RESORT CELL REPLACEMENT

5189
03:42:51,549 --> 03:42:51,816
THERAPIES.

5190
03:42:51,816 --> 03:42:54,352
MAYBE WE SHOULD BE THINKING

5191
03:42:54,352 --> 03:42:54,852
ABOUT LONGEVITY.

5192
03:42:54,852 --> 03:42:57,088
AND MAYBE THE FUTURE OF

5193
03:42:57,088 --> 03:42:59,323
REGENERATIVE MEDICINE IS

5194
03:42:59,323 --> 03:43:03,528
COUPLING WITH THE ANTI-AGING 

5195
03:43:03,528 --> 03:43:04,262
GURUS AND PHARMACEUTICAL

5196
03:43:04,262 --> 03:43:04,695
EXPERTS.

5197
03:43:04,695 --> 03:43:08,432
AND SO THE WAY I TRY RATIONALIZE

5198
03:43:08,432 --> 03:43:10,401
THIS, YOU REMEMBER GRADE SCHOOL

5199
03:43:10,401 --> 03:43:10,668
MATH.

5200
03:43:10,668 --> 03:43:12,270
YOUR TEACHER WOULD EXPLAIN TO

5201
03:43:12,270 --> 03:43:15,873
YOU A MILLION TIMES ZERO IS

5202
03:43:15,873 --> 03:43:16,073
ZERO.

5203
03:43:16,073 --> 03:43:18,342
BUT, YOU KNOW, 100 TIMES A

5204
03:43:18,342 --> 03:43:19,810
MILLION IS 100 MILLION.

5205
03:43:19,810 --> 03:43:24,815
SO IF WE WAIT TILL TISSUE IS SO

5206
03:43:24,815 --> 03:43:25,816
DEGRADED THERE'S ZERO

5207
03:43:25,816 --> 03:43:26,717
REGENERATIVE CAPABILITY, A

5208
03:43:26,717 --> 03:43:28,286
MILLION TIMES ZERO IS ZERO.

5209
03:43:28,286 --> 03:43:30,855
IF WE START INTERVENING EARLY,

5210
03:43:30,855 --> 03:43:32,523
WELL, THEN, A MILLION TIMES

5211
03:43:32,523 --> 03:43:34,258
WHATEVER IS LEFT COULD BE QUITE

5212
03:43:34,258 --> 03:43:34,692
MEANINGFUL.

5213
03:43:34,692 --> 03:43:36,661
I THINK THAT'S THE FIRST THING.

5214
03:43:36,661 --> 03:43:38,429
I THINK WE NEED TO INTERVENE

5215
03:43:38,429 --> 03:43:40,097
EARLY, AND MAYBE STOP THINKING

5216
03:43:40,097 --> 03:43:42,800
ABOUT JUST CELL REPLACEMENT AS

5217
03:43:42,800 --> 03:43:44,368
AN END STAGE STRATEGY.

5218
03:43:44,368 --> 03:43:47,271
THE SECOND POINT I WANTED TO TO

5219
03:43:47,271 --> 03:43:49,907
MAKE MAYBE WE SHOULD THINK ABOUT

5220
03:43:49,907 --> 03:43:51,976
SYNTHETIC CELLS, MAYBE SOMETHING

5221
03:43:51,976 --> 03:43:52,944
THE NIH CAN SUPPORT.

5222
03:43:52,944 --> 03:43:55,146
THERE WAS DISCUSSION ABOUT WHAT

5223
03:43:55,146 --> 03:43:57,014
IS THE IDEAL PHENOTYPE.

5224
03:43:57,014 --> 03:43:59,183
WELL, MAYBE THE IDEAL PHENOTYPE

5225
03:43:59,183 --> 03:44:02,053
IS NOT AN MSC, NOT A MACROPHAGE,

5226
03:44:02,053 --> 03:44:03,921
MAYBE IT'S SOMETHING ELSE

5227
03:44:03,921 --> 03:44:06,524
ALTOGETHER. 

5228
03:44:06,524 --> 03:44:09,827
IN THE MSC FIELD, I THINK OUR

5229
03:44:09,827 --> 03:44:12,797
COLLEAGUE HERE FROM ONE OF THE

5230
03:44:12,797 --> 03:44:14,098
CELL THERAPY DEPARTMENTS

5231
03:44:14,098 --> 03:44:14,865
MENTIONED HOW MANY FAILED

5232
03:44:14,865 --> 03:44:16,634
STUDIES THERE WERE.

5233
03:44:16,634 --> 03:44:17,668
THERE'S THOUSANDS, RIGHT?

5234
03:44:17,668 --> 03:44:19,904
AND I HAVE A COLLEAGUE AT

5235
03:44:19,904 --> 03:44:21,872
ASTRAZENECA WHO HAS DONE

5236
03:44:21,872 --> 03:44:25,543
INTERESTING WORK, HE SHOWS WHEN

5237
03:44:25,543 --> 03:44:26,844
MSCs ARE INFUSED INTRAVENOUSLY

5238
03:44:26,844 --> 03:44:31,816
MOST GO THROUGH APOPTOSIS RIGHT

5239
03:44:31,816 --> 03:44:32,049
AWAY.

5240
03:44:32,049 --> 03:44:35,886
IN FACT, APOPTOSIS, BY THE

5241
03:44:35,886 --> 03:44:37,355
MACROPHAGES, PROBABLY ELICITING

5242
03:44:37,355 --> 03:44:39,123
THE IMMUNE DAMPENING RESPONSE,

5243
03:44:39,123 --> 03:44:40,291
INTERESTING BUT PROBABLY NOT

5244
03:44:40,291 --> 03:44:40,524
IDEAL.

5245
03:44:40,524 --> 03:44:43,561
THAT'S PROBABLY NOT WHAT YOU

5246
03:44:43,561 --> 03:44:44,996
WANTED.

5247
03:44:44,996 --> 03:44:46,330
SO INSTEAD I THINK THE IDEA THAT

5248
03:44:46,330 --> 03:44:47,932
THOUSANDS OF STUDIES AND

5249
03:44:47,932 --> 03:44:49,900
THOUSANDS OF INVESTIGATORS HAD

5250
03:44:49,900 --> 03:44:54,171
THAT WE WANT TO USE SIGNALS TO

5251
03:44:54,171 --> 03:44:55,006
UPREGULATE INTRINSIC REPAIR

5252
03:44:55,006 --> 03:44:56,173
PROCESS, I THINK THAT WAS ALL

5253
03:44:56,173 --> 03:44:56,440
RIGHT.

5254
03:44:56,440 --> 03:45:00,411
BUT I THINK INSTEAD OF USING AN

5255
03:45:00,411 --> 03:45:03,681
MSC WE SHOULD ACTUALLY

5256
03:45:03,681 --> 03:45:04,582
COMPLETELY SYNTHETICALLY

5257
03:45:04,582 --> 03:45:05,883
ENGINEER THE CELL TO SECRETE

5258
03:45:05,883 --> 03:45:09,286
WHAT WE WANT AND NOW WHEN THE

5259
03:45:09,286 --> 03:45:11,122
IMMUNE CELL THERAPY CAME GEAR AT

5260
03:45:11,122 --> 03:45:12,490
MAKING SURE CELLS GO WHERE WE

5261
03:45:12,490 --> 03:45:13,024
WANT.

5262
03:45:13,024 --> 03:45:14,425
SO WE SHOULD ENGINEER CELLS TO

5263
03:45:14,425 --> 03:45:15,993
GO WHETHER WE WANT AND SECRETE

5264
03:45:15,993 --> 03:45:16,861
WHAT WE WANT.

5265
03:45:16,861 --> 03:45:18,362
WE SHOULD DO IT EARLIER.

5266
03:45:18,362 --> 03:45:22,533
SO THAT'S BASICALLY MY MESSAGE

5267
03:45:22,533 --> 03:45:22,733
TODAY.

5268
03:45:22,733 --> 03:45:24,702
AND I THOUGHT, YOU KNOW, MAYBE

5269
03:45:24,702 --> 03:45:26,937
WE CAN MAKE MORE MONEY IF WE

5270
03:45:26,937 --> 03:45:30,541
ENTER THE ANTI-AGING GAME, SO I

5271
03:45:30,541 --> 03:45:32,843
THOUGHT I WOULD PUT THAT IN

5272
03:45:32,843 --> 03:45:33,244
THERE.

5273
03:45:33,244 --> 03:45:33,711
OKAY, THANKS, GUYS.

5274
03:45:33,711 --> 03:45:36,914
>> THANK YOU VERY MUCH.

5275
03:45:36,914 --> 03:45:45,723
UP NEXT WE HAVE MARINNA MADRID.

5276
03:45:45,723 --> 03:45:49,226
>> THANK YOU.

5277
03:45:49,226 --> 03:45:51,862
CO-FOUNDER AND CHIEF PRODUCT

5278
03:45:51,862 --> 03:45:52,730
OFFICER AT CELLINO.

5279
03:45:52,730 --> 03:45:55,700
I WAS EXCITED TO TALK ABOUT

5280
03:45:55,700 --> 03:45:56,934
AUTOLOGOUS THERAPY, WE'RE

5281
03:45:56,934 --> 03:45:58,502
BUILDING A BIOMANUFACTURING

5282
03:45:58,502 --> 03:46:01,338
PLATFORM TO SCALE PRODUCTION OF

5283
03:46:01,338 --> 03:46:02,973
AUTOLOGOUS iPSCs.

5284
03:46:02,973 --> 03:46:05,476
AND A QUICK NOTE ON AN EXAMPLE

5285
03:46:05,476 --> 03:46:07,745
OF CELL THERAPY THAT I THINK

5286
03:46:07,745 --> 03:46:09,080
SHOWS WHY MANUFACTURING

5287
03:46:09,080 --> 03:46:10,481
INNOVATION IS IMPORTANT, THE CAR

5288
03:46:10,481 --> 03:46:11,615
T SPACE.

5289
03:46:11,615 --> 03:46:15,986
WE SAW LIKE REMARKABLE CLINICAL

5290
03:46:15,986 --> 03:46:17,488
EFFICACY, CANCERS CURED.

5291
03:46:17,488 --> 03:46:18,055
WE'RE BASED IN BOSTON.

5292
03:46:18,055 --> 03:46:20,024
IF YOU GO TO A TOP HOSPITAL IN

5293
03:46:20,024 --> 03:46:21,058
BOSTON TODAY, OF THE TEN

5294
03:46:21,058 --> 03:46:23,294
PATIENTS THAT NEED A LIFE-SAVING

5295
03:46:23,294 --> 03:46:25,029
CAR T THERAPY, ABOUT TWO ARE AGE

5296
03:46:25,029 --> 03:46:27,298
TO GET ACCESS TO IT BECAUSE OF

5297
03:46:27,298 --> 03:46:28,132
MANUFACTURING BOTTLENECKS.

5298
03:46:28,132 --> 03:46:31,435
AND SO WE DON'T WANT THAT SCALE

5299
03:46:31,435 --> 03:46:34,739
CHALLENGE TO HAPPEN IN THE PSC

5300
03:46:34,739 --> 03:46:35,039
SPACE.

5301
03:46:35,039 --> 03:46:37,341
AND SO MANY OF YOU ARE AWARE OF

5302
03:46:37,341 --> 03:46:39,410
THE CHALLENGES WITH iPSC

5303
03:46:39,410 --> 03:46:40,911
MANUFACTURING, IT'S VERY MANUAL

5304
03:46:40,911 --> 03:46:42,146
LABOR INTENSIVE PROCESS,

5305
03:46:42,146 --> 03:46:43,781
DEPENDENT ON EXTREMELY SKILLED

5306
03:46:43,781 --> 03:46:44,148
OPERATORS.

5307
03:46:44,148 --> 03:46:46,517
WHAT WE'RE DOING IS AUTOMATING

5308
03:46:46,517 --> 03:46:47,852
THE PROCESS BY TAKING OPTICAL

5309
03:46:47,852 --> 03:46:48,219
APPROACH.

5310
03:46:48,219 --> 03:46:52,556
IF YOU CAN IMAGINE THESE CELL

5311
03:46:52,556 --> 03:46:53,524
CULTURE PROCESSES, ADHERENT CELL

5312
03:46:53,524 --> 03:46:55,526
CULTURE SERVICE, WE IMAGE THE

5313
03:46:55,526 --> 03:46:58,162
CELLS REGULARLY, WE DEVELOP OUR

5314
03:46:58,162 --> 03:46:59,463
OTHER THAN IMAGE-GUIDED MACHINE

5315
03:46:59,463 --> 03:47:00,231
ALGORITHMS THAT CHARACTERIZE

5316
03:47:00,231 --> 03:47:07,705
CELLS AND USE A LASER TO

5317
03:47:07,705 --> 03:47:09,140
ESSENTIALLY REMOVE UNWANTED

5318
03:47:09,140 --> 03:47:10,875
CELLS, MAYBE TO REMOVE ALL BUT

5319
03:47:10,875 --> 03:47:14,912
ONE COLONY TO RESULT IN A MORE

5320
03:47:14,912 --> 03:47:15,913
PURE POPULATION BUT IMAGE-GUIDED

5321
03:47:15,913 --> 03:47:17,848
MACHINE LEARNING IS USED TO MAKE

5322
03:47:17,848 --> 03:47:19,383
BETTER IN-PROCESS DECISIONS SUCH

5323
03:47:19,383 --> 03:47:23,354
AS WHAT CELLS TO REMOVE.

5324
03:47:23,354 --> 03:47:23,988
WE'RE TAKING A

5325
03:47:23,988 --> 03:47:25,723
MULTI-DISCIPLINARY APPROACH.

5326
03:47:25,723 --> 03:47:27,658
OUR TEAM IS MULTI-DISCIPLINARY,

5327
03:47:27,658 --> 03:47:35,432
MY BACKGROUND, Ph.D. IN

5328
03:47:35,432 --> 03:47:37,234
APPLIED PHYSICS, THIS SHOWS OUR

5329
03:47:37,234 --> 03:47:41,472
LAB FACILITY, TWO AUTOMATED WORK

5330
03:47:41,472 --> 03:47:42,706
CELLS, HEPA FILTERED ENCLOSURE,

5331
03:47:42,706 --> 03:47:44,041
BSL2 LAB.

5332
03:47:44,041 --> 03:47:47,978
WE HAVE WELL PLATES, ROBOTIC ARM

5333
03:47:47,978 --> 03:47:52,917
THAT MOVES FROM SUBSYSTEM TO

5334
03:47:52,917 --> 03:47:54,418
SUBSYSTEM, AUTOMATED INCUBATION,

5335
03:47:54,418 --> 03:47:55,986
IMAGING, LASER SCANNING, WHAT

5336
03:47:55,986 --> 03:47:57,421
WE'RE USING AUTOMATED WORK CELLS

5337
03:47:57,421 --> 03:48:00,357
TO DO IS DEVELOP AUTOMATED

5338
03:48:00,357 --> 03:48:02,660
REPROGRAMMING PROCESSES, SO WE

5339
03:48:02,660 --> 03:48:07,231
DEVELOPED FIRST AUTOMATED PSC

5340
03:48:07,231 --> 03:48:08,432
GENERATION PROCESS USING CD34

5341
03:48:08,432 --> 03:48:10,835
POSITIVE CELLS, TAKING LARGE

5342
03:48:10,835 --> 03:48:11,836
VOLUMES OF IMAGING TRAINING DATA

5343
03:48:11,836 --> 03:48:12,803
TO DEVELOP MACHINE LEARNING

5344
03:48:12,803 --> 03:48:13,504
ALGORITHMS.

5345
03:48:13,504 --> 03:48:15,439
WE HAVE A GRAPHICAL USER

5346
03:48:15,439 --> 03:48:16,407
INTERFACE, STEM CELL SCIENTISTS

5347
03:48:16,407 --> 03:48:18,008
USE TO INTERACT WITH IMAGES THAT

5348
03:48:18,008 --> 03:48:20,177
HAVE BEEN TAKEN AND THEY CAN

5349
03:48:20,177 --> 03:48:21,178
ALSO MAKE IN-PROCESS DECISIONS

5350
03:48:21,178 --> 03:48:21,712
IF NEEDED.

5351
03:48:21,712 --> 03:48:25,516
IT DOESN'T NEED TO BE A FULLY

5352
03:48:25,516 --> 03:48:26,717
AUTONOMOUS PROCESS, STEM CELL

5353
03:48:26,717 --> 03:48:28,118
SCIENTISTS CAN INTERACT.

5354
03:48:28,118 --> 03:48:29,687
THIS IS KATHERINE, A SCIENTIST

5355
03:48:29,687 --> 03:48:31,655
LOOKING AT COLONIES THAT HAVE

5356
03:48:31,655 --> 03:48:32,590
BEEN IDENTIFIED.

5357
03:48:32,590 --> 03:48:33,891
WE HAVE A DASHBOARD.

5358
03:48:33,891 --> 03:48:40,497
HUMANS ARE NOT ALLOWED INTO THE

5359
03:48:40,497 --> 03:48:41,732
HEPA FILTERED ENCLOSE YOU'RE, WE

5360
03:48:41,732 --> 03:48:43,133
HAVE A DASHBOARD THAT TELLS WHAT

5361
03:48:43,133 --> 03:48:44,335
EXPERIMENTS ARE HAPPENING THAT

5362
03:48:44,335 --> 03:48:45,102
DAY.

5363
03:48:45,102 --> 03:48:48,505
I WANTED TO GIVE A SENSE OF WHAT

5364
03:48:48,505 --> 03:48:49,039
IT LOOK LIKE.

5365
03:48:49,039 --> 03:48:52,877
ON THE LEFT THE AUTOMATED WORK

5366
03:48:52,877 --> 03:48:57,114
CELL, IN A BSL2 SETTING, OPEN

5367
03:48:57,114 --> 03:48:59,216
WELL PLATE FORMAT FOR R&D

5368
03:48:59,216 --> 03:48:59,917
DEVELOPMENT.

5369
03:48:59,917 --> 03:49:01,518
WHAT'S NICE ABOUT THE OPTICAL

5370
03:49:01,518 --> 03:49:03,187
APPROACH, IMAGE-GUIDED MACHINE

5371
03:49:03,187 --> 03:49:04,922
LEARNING AND LASER-BASED REMOVAL

5372
03:49:04,922 --> 03:49:06,657
OF CELLS, BOTH PROCESS ARE

5373
03:49:06,657 --> 03:49:07,858
COMPATIBLE WITH CLOSED

5374
03:49:07,858 --> 03:49:09,727
MANUFACTURING IN A WAY THAT

5375
03:49:09,727 --> 03:49:11,061
MANUAL SCRAPING JUST IS NOT.

5376
03:49:11,061 --> 03:49:12,796
SO WHAT WE'RE DOING IN PARALLEL

5377
03:49:12,796 --> 03:49:15,466
TO RUNNING THE AUTOMATED R&D

5378
03:49:15,466 --> 03:49:19,503
WORK CELL, WE'RE BUILDING A

5379
03:49:19,503 --> 03:49:21,805
CLINICAL-GRADE GMP MANUFACTURING

5380
03:49:21,805 --> 03:49:23,974
SYSTEM, GMP COMPLIANT, BASED ON

5381
03:49:23,974 --> 03:49:24,742
CLOSED CASSETTES.

5382
03:49:24,742 --> 03:49:26,610
SO USES THE SAME IMAGE GUIDED

5383
03:49:26,610 --> 03:49:27,912
MACHINE LEARNING, SAME LASER

5384
03:49:27,912 --> 03:49:29,914
PROCESSING BUT THE WAY FLUIDICS

5385
03:49:29,914 --> 03:49:31,448
ARE INTRODUCED TO CELLS ARE

5386
03:49:31,448 --> 03:49:33,284
DIFFERENT IN A CLOSED CONTAINER.

5387
03:49:33,284 --> 03:49:36,353
SO THIS IS SORT OF WORKFLOW ON

5388
03:49:36,353 --> 03:49:37,354
THE IMAGE-GUIDED MACHINE

5389
03:49:37,354 --> 03:49:37,988
LEARNING SIDE.

5390
03:49:37,988 --> 03:49:40,190
EXAMPLE OF WHAT YOU MIGHT DO IS

5391
03:49:40,190 --> 03:49:41,759
TAKE A BRIGHT FIELD IMAGE OF

5392
03:49:41,759 --> 03:49:42,259
CELLS.

5393
03:49:42,259 --> 03:49:45,663
WE HAVE ALGORITHMS THAT CAN

5394
03:49:45,663 --> 03:49:47,131
AUTOMATICALLY DETECT CONFLUENCE,

5395
03:49:47,131 --> 03:49:51,368
PREDICT EXPRESSION OF PLEURY

5396
03:49:51,368 --> 03:49:52,770
POTENCY MARKERS, A WAY OF

5397
03:49:52,770 --> 03:49:54,405
IDENTIFYING IF THEY ARE

5398
03:49:54,405 --> 03:49:56,840
DIFFERENTIATING, GET A MAYBE OF

5399
03:49:56,840 --> 03:50:00,444
LOCAL DENSITY, GENERATE LASER

5400
03:50:00,444 --> 03:50:01,679
SCANNING MAPS, MIGHT SEE

5401
03:50:01,679 --> 03:50:02,846
DIFFERENTIALING CELLS, LET'S

5402
03:50:02,846 --> 03:50:06,684
REMOVE THOSE, THIS AREA IS

5403
03:50:06,684 --> 03:50:07,551
BECOMING OVERLY DENSE, LET'S

5404
03:50:07,551 --> 03:50:14,458
LASER REMOVE AND THIN IT OUT.

5405
03:50:14,458 --> 03:50:15,759
THIS IS A COMPLICATED ONE TO

5406
03:50:15,759 --> 03:50:16,293
EXPLAIN.

5407
03:50:16,293 --> 03:50:17,962
TAKE A STEP BACK.

5408
03:50:17,962 --> 03:50:20,130
TO ENABLE THIS CLOSED

5409
03:50:20,130 --> 03:50:23,734
MANUFACTURING, WE HAD TO DEVELOP

5410
03:50:23,734 --> 03:50:24,868
A PASSAGE-FREE PROCESS.

5411
03:50:24,868 --> 03:50:28,806
YOU NEED TO ALLOW CERTAIN NUMBER

5412
03:50:28,806 --> 03:50:32,276
OF CELL DIVISIONS FOR VECTOR TO

5413
03:50:32,276 --> 03:50:33,043
CLEAR, NORMALLY MOVING ONE TO

5414
03:50:33,043 --> 03:50:33,410
ANOTHER.

5415
03:50:33,410 --> 03:50:35,779
BUT WE HAVE A CLOSED SYSTEM AND

5416
03:50:35,779 --> 03:50:37,181
CAN'T MOVE CELLS FROM ONE WELL

5417
03:50:37,181 --> 03:50:39,116
TO ANOTHER.

5418
03:50:39,116 --> 03:50:41,151
THEY HAVE TO STAY IN THE SAME

5419
03:50:41,151 --> 03:50:43,654
SURFACE AREA.

5420
03:50:43,654 --> 03:50:52,863
WE DEVELOPED A PASSAGE-FREE

5421
03:50:52,863 --> 03:50:53,497
PROCESS.

5422
03:50:53,497 --> 03:50:58,202
AS COLONIES GROW BIGGER WE LASER

5423
03:50:58,202 --> 03:50:59,737
REMOVE -- BLUE IS LASER REMOVE,

5424
03:50:59,737 --> 03:51:02,272
REMOVE A PIECE OF THE COLONY SO

5425
03:51:02,272 --> 03:51:03,574
REMAINING CELLS WITH GROW AND

5426
03:51:03,574 --> 03:51:04,908
DIVIDE, OVER AND OVER AGAIN,

5427
03:51:04,908 --> 03:51:06,643
UNTIL THE CELLS HAVE GONE

5428
03:51:06,643 --> 03:51:08,612
THROUGH ENOUGH DIVISIONS TO

5429
03:51:08,612 --> 03:51:10,881
CLEAR THE REPROGRAMMING VECTOR.

5430
03:51:10,881 --> 03:51:12,549
SO ONE REASON WE DO THIS IS

5431
03:51:12,549 --> 03:51:15,052
ENABLE CLOSED MANUFACTURING.

5432
03:51:15,052 --> 03:51:18,555
THE OTHER HYPOTHESIS IF WE TAKE

5433
03:51:18,555 --> 03:51:20,724
ENOUGH TIME-BASED SERIES DATA

5434
03:51:20,724 --> 03:51:21,425
THROUGH THE 60-DAY REPROGRAMMING

5435
03:51:21,425 --> 03:51:23,060
PROCESS WE WILL BE ABLE TO -- WE

5436
03:51:23,060 --> 03:51:26,897
AIM TO BE ABLE TO CONNECT ON

5437
03:51:26,897 --> 03:51:28,198
IMAGE-BASED DATA TO MEASUREMENTS

5438
03:51:28,198 --> 03:51:29,433
OF QUALITY AT THE END.

5439
03:51:29,433 --> 03:51:31,268
FOR EXAMPLE, BY SAYING, OH, THIS

5440
03:51:31,268 --> 03:51:33,437
COLONY HAS A GROWTH AND

5441
03:51:33,437 --> 03:51:34,671
PROLIFERATION THAT'S ABNORMAL

5442
03:51:34,671 --> 03:51:45,182
AND THEREFORE MORE LIKELY TO 

5443
03:51:49,153 --> 03:51:50,587
KEROTYPICALLY DIFFERENT.

5444
03:51:50,587 --> 03:51:52,089
EVERYTHING IS DOING SOMETHING

5445
03:51:52,089 --> 03:51:52,823
SLIGHTLY DIFFERENT ON GENOMIC

5446
03:51:52,823 --> 03:51:54,324
STABILITY BUT THE REASON I MAKE

5447
03:51:54,324 --> 03:51:56,760
THIS POINT IS WE'RE USING

5448
03:51:56,760 --> 03:51:58,495
IMAGE-GUIDED MACHINE LEARNING TO

5449
03:51:58,495 --> 03:52:00,164
MAKE IN-PROCESS DECISION, NOT TO

5450
03:52:00,164 --> 03:52:01,432
REPLACE END STAGE RELEASE

5451
03:52:01,432 --> 03:52:01,732
TESTING.

5452
03:52:01,732 --> 03:52:03,300
I WOULD LOVE TO SEE THE INDUSTRY

5453
03:52:03,300 --> 03:52:04,768
MOVE THAT DIRECTION, BUT THAT

5454
03:52:04,768 --> 03:52:06,403
WILL TAKE MORE DATA.

5455
03:52:06,403 --> 03:52:08,272
AND THESE ARE PROTOTYPES OF THE

5456
03:52:08,272 --> 03:52:11,975
FLUIDIC CASSETTES FOR CLOSED

5457
03:52:11,975 --> 03:52:12,209
SYSTEM.

5458
03:52:12,209 --> 03:52:13,110
I'M GOING TO SKIP TO THE

5459
03:52:13,110 --> 03:52:14,611
QUESTIONS THAT WOULD BE

5460
03:52:14,611 --> 03:52:15,546
INTERESTING FOR POTENTIAL

5461
03:52:15,546 --> 03:52:16,413
RESEARCH AREAS.

5462
03:52:16,413 --> 03:52:18,115
ONE IS ESTABLISHING SET OF

5463
03:52:18,115 --> 03:52:19,483
STANDARD IDESSED QUALITY

5464
03:52:19,483 --> 03:52:20,851
SPECIFIC CASES AT THE iPSC

5465
03:52:20,851 --> 03:52:21,085
STAGE.

5466
03:52:21,085 --> 03:52:23,353
RIGHT NOW IF YOU START A

5467
03:52:23,353 --> 03:52:24,788
CLINICAL TRIAL, YOU START WITH A

5468
03:52:24,788 --> 03:52:26,657
CERTAIN STARTING MATERIAL OR

5469
03:52:26,657 --> 03:52:27,291
CERTAIN REPROGRAMMING VECTOR,

5470
03:52:27,291 --> 03:52:28,525
YOU WANT TO MOVE TO A NEW

5471
03:52:28,525 --> 03:52:30,394
STARTING MATERIAL OR NEW

5472
03:52:30,394 --> 03:52:31,528
REPROGRAMMING VECTOR FOR THE

5473
03:52:31,528 --> 03:52:36,934
NEXT PHASE THAT WOULD BE -- 

5474
03:52:36,934 --> 03:52:39,136
WOULD TRIGGER DEFINITION OF NEW

5475
03:52:39,136 --> 03:52:40,104
PRODUCT REQUIRING NEW IND.

5476
03:52:40,104 --> 03:52:41,572
IF WE COULD AGREE ON STANDARDS,

5477
03:52:41,572 --> 03:52:44,475
THAT COULD BE THE BASIS FOR

5478
03:52:44,475 --> 03:52:45,676
ENABLING INTERCHANGEABILITY

5479
03:52:45,676 --> 03:52:48,011
WHICH WOULD RESULT IN MORE COST

5480
03:52:48,011 --> 03:52:49,446
EFFECTIVE, MORE TIMELY DRUG

5481
03:52:49,446 --> 03:52:49,746
DEVELOPMENT.

5482
03:52:49,746 --> 03:52:53,584
RELATED TO THAT ON THE GENOMIC

5483
03:52:53,584 --> 03:52:54,751
STABILITY SIDE, DIFFERENT

5484
03:52:54,751 --> 03:52:55,552
POPULATIONS OF PATIENTS CAN

5485
03:52:55,552 --> 03:52:56,653
ACCEPT DIFFERENT LEVELS OF RISK,

5486
03:52:56,653 --> 03:52:59,056
BUT I THINK IT WOULD BE AMAZING

5487
03:52:59,056 --> 03:53:02,359
TO DO A MASSIVE META-ANALYSIS

5488
03:53:02,359 --> 03:53:04,161
BASED ON LITERATURE SEARCHES, IN

5489
03:53:04,161 --> 03:53:05,195
VITRO AND IN VIVO EXPERIMENTS TO

5490
03:53:05,195 --> 03:53:06,830
SAY HERE IS THE LIST OF

5491
03:53:06,830 --> 03:53:08,699
ONCOGENES, IF YOU HAVE THIS

5492
03:53:08,699 --> 03:53:10,134
MUTATION AND THAT ONCOGENE THIS

5493
03:53:10,134 --> 03:53:13,203
IS THE ASSESSMENT OF RISK

5494
03:53:13,203 --> 03:53:15,272
BECAUSE RIGHT NOW DIFFERENT

5495
03:53:15,272 --> 03:53:16,907
DEVELOPERS ARE MAKING THESE

5496
03:53:16,907 --> 03:53:18,709
JUDGMENTS BASED ON THEIR OWN

5497
03:53:18,709 --> 03:53:19,743
LITERATURE SEARCHES, IT WOULD BE

5498
03:53:19,743 --> 03:53:23,814
NICE TO HAVE A CONSENSUS FOR THE

5499
03:53:23,814 --> 03:53:25,215
FIELD.

5500
03:53:25,215 --> 03:53:26,316
ANOTHER WHY THE WHAT DATA WOULD

5501
03:53:26,316 --> 03:53:28,385
WE NEED TO ESTABLISH A SAFE

5502
03:53:28,385 --> 03:53:31,922
OPERATING SPACE FOR A.I.-BASED

5503
03:53:31,922 --> 03:53:33,524
OPERATING PROCESSES MOTIVATED BY

5504
03:53:33,524 --> 03:53:38,162
MEDICAL DEVICE FIELD. 

5505
03:53:38,162 --> 03:53:39,696
CELL THERAPY MORE LIKE DEVICES

5506
03:53:39,696 --> 03:53:43,400
THAN SMALL MOL  MOLECULES.

5507
03:53:43,400 --> 03:53:45,169
THEY ARE MUCH MORE COMPLEX AND

5508
03:53:45,169 --> 03:53:46,670
IN THE MEDICAL DEVICE SPACE

5509
03:53:46,670 --> 03:53:49,206
MEDICAL DEVICES ARE NOT STATIC.

5510
03:53:49,206 --> 03:53:50,174
MEDICAL DEVICE COMPANIES WILL

5511
03:53:50,174 --> 03:53:52,476
UPDATE THEIR ALGORITHMS AND BE

5512
03:53:52,476 --> 03:53:54,378
ABLE TO BASICALLY MAKE MEDICAL

5513
03:53:54,378 --> 03:53:55,112
DEVICES BETTER, IT DOESN'T

5514
03:53:55,112 --> 03:53:57,080
REQUIRE THEM TO DO AN ENTIRELY

5515
03:53:57,080 --> 03:53:58,215
NEW CLINICAL TRIAL BECAUSE UP

5516
03:53:58,215 --> 03:53:59,917
FRONT THEY HAVE ESTABLISHED A

5517
03:53:59,917 --> 03:54:01,351
SAFE OPERATING SPACE WHERE THEY

5518
03:54:01,351 --> 03:54:03,654
SAY IF WE ARE WITHIN THAT SAFE

5519
03:54:03,654 --> 03:54:04,988
OPERATING SPACE WE CAN CONTINUE

5520
03:54:04,988 --> 03:54:06,290
TO MAKE IMPROVEMENTS TO THIS

5521
03:54:06,290 --> 03:54:08,458
PROCESS AND THAT IS STILL

5522
03:54:08,458 --> 03:54:08,759
ACCEPTABLE.

5523
03:54:08,759 --> 03:54:11,428
SO I THINK THAT THINKING ABOUT

5524
03:54:11,428 --> 03:54:12,963
SAFE OPERATING SPACE WITHIN THE

5525
03:54:12,963 --> 03:54:15,365
CONTEXT OF CELL THERAPY

5526
03:54:15,365 --> 03:54:17,067
MANUFACTURING WOULD BE

5527
03:54:17,067 --> 03:54:17,601
BENEFICIAL.

5528
03:54:17,601 --> 03:54:19,536
THE LAST THING I HAVE HERE, OH,

5529
03:54:19,536 --> 03:54:21,405
POINT NUMBER 2 WHICH I SKIPPED

5530
03:54:21,405 --> 03:54:29,479
OVER, COULD  HOW CAN CAN WE

5531
03:54:29,479 --> 03:54:32,583
REPLACE END STAGE PROCESSING,

5532
03:54:32,583 --> 03:54:34,851
REQUIRING ADVANCEMENTS IN

5533
03:54:34,851 --> 03:54:35,652
MACHINE LEARNING BUT GET

5534
03:54:35,652 --> 03:54:37,020
THERAPIES TO PATIENTS IN A

5535
03:54:37,020 --> 03:54:38,789
TIMELY MANNER AND COST EFFECTIVE

5536
03:54:38,789 --> 03:54:39,223
MANNER

5537
03:54:39,223 --> 03:54:42,392
WHAT IT WILL REQUIRE IS

5538
03:54:42,392 --> 03:54:43,927
ESSENTIALLY CORRELATED IN

5539
03:54:43,927 --> 03:54:44,828
PROCESS ANALYTICS SUCH AS

5540
03:54:44,828 --> 03:54:48,865
MACHINE LEARNING WITH END STAGE

5541
03:54:48,865 --> 03:54:54,438
TESTING SUCH AS KERYO TYPING.

5542
03:54:54,438 --> 03:55:01,445
THAT WAS EVERYTHING.

5543
03:55:01,445 --> 03:55:06,383
THANK YOU. 

5544
03:55:06,383 --> 03:55:09,219
ON DECK RICH McFARLAND.

5545
03:55:09,219 --> 03:55:13,690
 

5546
03:55:13,690 --> 03:55:17,127
 

5547
03:55:17,127 --> 03:55:27,170
 

5548
03:55:28,839 --> 03:55:33,010
>> I WAS ASKED TO GIVE A
NEEDS

5549
03:55:33,010 --> 03:55:34,278
FOR INTEGRATED NIH/FEDERAL

5550
03:55:34,278 --> 03:55:42,319
APPROACH TO REGENERATIVE

5551
03:55:42,319 --> 03:55:43,487
MEDICINE, I'M CHIEF OPERATING

5552
03:55:43,487 --> 03:55:45,889
OFFICER ON THE ARMI, I'M AT A

5553
03:55:45,889 --> 03:55:49,192
HALFWAY HOUSE FROM BEING AT FDA,

5554
03:55:49,192 --> 03:55:51,461
I'M GOING TO TRY TO MIX THOSE

5555
03:55:51,461 --> 03:55:54,364
TWO EXPERIENCES AND TELL YOU

5556
03:55:54,364 --> 03:55:56,533
WHAT I THINK.

5557
03:55:56,533 --> 03:55:58,035
I USED THIS TO REMIND MYSELF

5558
03:55:58,035 --> 03:56:01,738
THAT CELLS AND TISSUES ARE

5559
03:56:01,738 --> 03:56:02,639
COMPLICATED.

5560
03:56:02,639 --> 03:56:05,575
A COUPLE ORDER OF MAGNITUDES

5561
03:56:05,575 --> 03:56:06,376
MORE COMPLICATED THAN GENE

5562
03:56:06,376 --> 03:56:06,910
THERAPY.

5563
03:56:06,910 --> 03:56:09,713
I CAN'T BELIEVE I'M SAYING THIS,

5564
03:56:09,713 --> 03:56:12,683
SIMPLE GENE THERAPY.

5565
03:56:12,683 --> 03:56:16,753
IT ISN'T SIMPLE BUT IT'S SIMPLE

5566
03:56:16,753 --> 03:56:18,088
COMPARED TO THE TALKS THIS

5567
03:56:18,088 --> 03:56:23,894
MORNING ABOUT HOW DO YOU CONTROL

5568
03:56:23,894 --> 03:56:24,227
CELLS.

5569
03:56:24,227 --> 03:56:24,961
SOMETHING WE'VE BEEN WORRIED

5570
03:56:24,961 --> 03:56:26,263
ABOUT FOR A LONG TIME.

5571
03:56:26,263 --> 03:56:31,368
A GROUP GOING ON FOR 2 1/2 

5572
03:56:31,368 --> 03:56:32,869
DECADES OR SO, FOLKS ACROSS THE

5573
03:56:32,869 --> 03:56:34,037
FEDERAL GOVERNMENT, THIS IS A

5574
03:56:34,037 --> 03:56:37,541
STRATEGIC PLAN THAT GOT

5575
03:56:37,541 --> 03:56:39,176
PUBLISHED IN 2007, THOSE FOLKS

5576
03:56:39,176 --> 03:56:40,711
WITH ME IN THAT GROUP KNOW THAT

5577
03:56:40,711 --> 03:56:48,318
IT TOOK A WHILE TO GET THERE.

5578
03:56:48,318 --> 03:56:52,656
BUT THE ROAD MAP SPURRED FUNDING

5579
03:56:52,656 --> 03:56:55,726
FORMING THE ARMED FORCES

5580
03:56:55,726 --> 03:57:00,364
INSTITUTE OF REGENERATIVE 

5581
03:57:00,364 --> 03:57:04,067
MEDICINE, SUPPORTED NSF, ERCs,

5582
03:57:04,067 --> 03:57:11,341
SUCH AS C MAT, NINE YEARS AFTER

5583
03:57:11,341 --> 03:57:15,545
PUBLISHED SPURRED BIOFAB USA AND

5584
03:57:15,545 --> 03:57:17,748
NINBL, RELATED TO BIOTECHNOLOGY

5585
03:57:17,748 --> 03:57:18,949
AND REGENERATIVE MEDICINE, IT'S

5586
03:57:18,949 --> 03:57:23,019
CALLED TISSUE SCIENCE AND

5587
03:57:23,019 --> 03:57:24,221
ENGINEERING BECAUSE REGENERATIVE

5588
03:57:24,221 --> 03:57:26,189
MEDICINE DIDN'T EXIST WHEN THE

5589
03:57:26,189 --> 03:57:28,492
GROUP STARTED MEETING.

5590
03:57:28,492 --> 03:57:32,863
IT'S BEEN A FORMAL ORGANIZATION,

5591
03:57:32,863 --> 03:57:34,965
SHARING INFORMATION FOR 2 1/2

5592
03:57:34,965 --> 03:57:35,332
DECADES.

5593
03:57:35,332 --> 03:57:37,200
YOU SEE ALL THE AGENCIES THAT

5594
03:57:37,200 --> 03:57:41,605
HAVE BEEN LISTED AT THE TIME OF

5595
03:57:41,605 --> 03:57:42,606
THE PUBLICATION OF THE 2007

5596
03:57:42,606 --> 03:57:45,242
PLAN.

5597
03:57:45,242 --> 03:57:52,549
SO, THE BESPOKE GENE THERAPY

5598
03:57:52,549 --> 03:57:53,550
CONSORTIUM IS NOT COMPLICATED,

5599
03:57:53,550 --> 03:57:54,751
IT'S ALSO NOT SIMPLE.

5600
03:57:54,751 --> 03:57:57,487
I THINK I WILL SAY THIS IS A

5601
03:57:57,487 --> 03:58:01,658
GREAT EFFORT IN TERMS OF BOTH

5602
03:58:01,658 --> 03:58:02,826
PUBLIC AND PRIVATE PARTNERSHIP,

5603
03:58:02,826 --> 03:58:06,997
AND ARROWS BACK AND FORTH 

5604
03:58:06,997 --> 03:58:08,765
BETWEEN THE TWO AIMS.

5605
03:58:08,765 --> 03:58:12,702
ESSENTIAL FOR AN EFFORT TO GET

5606
03:58:12,702 --> 03:58:15,872
WITH CELL THERAPY ISSUE.

5607
03:58:15,872 --> 03:58:20,043
THE EXECUTIVE ORDER CAME OUT IN

5608
03:58:20,043 --> 03:58:23,747
22, THIS REPORT ON BOLD GOALS 

5609
03:58:23,747 --> 03:58:25,081
THAT CAME OUT IN 23.

5610
03:58:25,081 --> 03:58:29,252
AND YOU LOOK AT JUST COUPLE

5611
03:58:29,252 --> 03:58:31,955
HIGHLIGHTS FOR THE REGENERATIVE

5612
03:58:31,955 --> 03:58:33,623
MEDICINE SECTION, REGULATORY

5613
03:58:33,623 --> 03:58:35,158
PROCESS INCREASING CLARITY, AND

5614
03:58:35,158 --> 03:58:36,426
INCREASING EFFICIENCY, WE TALK

5615
03:58:36,426 --> 03:58:37,894
ABOUT THAT ALL THE TIME, WITH

5616
03:58:37,894 --> 03:58:40,497
FDA IT'S AN IMPORTANT DISCUSSION

5617
03:58:40,497 --> 03:58:41,598
TO HAVE WITH FDA.

5618
03:58:41,598 --> 03:58:44,000
THE THING THAT CAUGHT ME WHEN I

5619
03:58:44,000 --> 03:58:46,970
READ THIS WAS INCREASE THE

5620
03:58:46,970 --> 03:58:49,272
MANUFACTURING SCALE OF

5621
03:58:49,272 --> 03:58:52,442
CELL-BASED THERAPIES TEN FOLD

5622
03:58:52,442 --> 03:58:54,411
OVER 20 YEARS.

5623
03:58:54,411 --> 03:58:57,247
10-FOLD OVER 20 YEARS, THAT IS A

5624
03:58:57,247 --> 03:58:57,747
BOLD GOAL.

5625
03:58:57,747 --> 03:58:59,649
AND I THINK DOING WHAT WE'VE

5626
03:58:59,649 --> 03:59:07,190
BEEN DOING IN THE PAST, BREAKING

5627
03:59:07,190 --> 03:59:09,392
DOWN THE SILOS IS NEEDED TO GET

5628
03:59:09,392 --> 03:59:09,826
THERE.

5629
03:59:09,826 --> 03:59:13,864
THIS IS OFTEN SHOWN WITH RESPECT

5630
03:59:13,864 --> 03:59:16,132
TO INDIVIDUAL PRODUCTS AND

5631
03:59:16,132 --> 03:59:19,569
SO-CALLED VALLEY OF DEATH

5632
03:59:19,569 --> 03:59:21,738
BETWEEN THE INVESTIGATORS,

5633
03:59:21,738 --> 03:59:26,676
DISCOVERY SCIENCE, FUNDING, AND

5634
03:59:26,676 --> 03:59:28,111
INDUSTRY FUNDING.

5635
03:59:28,111 --> 03:59:29,112
IN REGENERATIVE MEDICINE PART OF

5636
03:59:29,112 --> 03:59:31,381
OUR GOAL IS TO START THE ENTIRE

5637
03:59:31,381 --> 03:59:33,450
INDUSTRY IF WE'RE GOING TO GET

5638
03:59:33,450 --> 03:59:38,488
CLOSE TO THE GOAL OF THE

5639
03:59:38,488 --> 03:59:39,356
BIOECONOMY.

5640
03:59:39,356 --> 03:59:41,458
GROWING THE WHOLE INDUSTRY IS

5641
03:59:41,458 --> 03:59:42,959
GREATER CHALLENGE THAN GROWING

5642
03:59:42,959 --> 03:59:44,327
INDIVIDUAL COMPANIES.

5643
03:59:44,327 --> 03:59:46,363
WE'VE TALKED ABOUT A LOT OF THE

5644
03:59:46,363 --> 03:59:49,466
CHALLENGES HERE, THEY RESONATE

5645
03:59:49,466 --> 03:59:50,433
WITH ME.

5646
03:59:50,433 --> 03:59:54,271
GAO DID A TECH ASSESSMENT LAST

5647
03:59:54,271 --> 03:59:56,673
YEAR, EARLIER THIS YEAR,

5648
03:59:56,673 --> 03:59:58,675
FINISHED UP NOTED CHALLENGES

5649
03:59:58,675 --> 04:00:00,544
RELATED TO STANDARD IDEATION,

5650
04:00:00,544 --> 04:00:02,045
RELATED TO STANDERIZATION AND

5651
04:00:02,045 --> 04:00:03,213
MANUFACTURING.

5652
04:00:03,213 --> 04:00:05,649
WHERE DOES THIS GET ME FOR

5653
04:00:05,649 --> 04:00:06,249
NEEDS?

5654
04:00:06,249 --> 04:00:06,883
CELL-BASED THERAPIES CONSORTIUM

5655
04:00:06,883 --> 04:00:11,021
SHOULD INCLUDE THE MATES 

5656
04:00:11,021 --> 04:00:11,788
AGENCIES, THAT'S GOVERNMENT

5657
04:00:11,788 --> 04:00:12,155
ONLY.

5658
04:00:12,155 --> 04:00:17,928
MANY OF THE PUBLIC AND PRIVATE 

5659
04:00:17,928 --> 04:00:19,763
PARTNERS IN THE BCTG, TC.

5660
04:00:19,763 --> 04:00:22,933
SHOULD LOOK AT THAT ASSESSMENT.

5661
04:00:22,933 --> 04:00:23,500
ADDITIONAL PARTICIPANTS,

5662
04:00:23,500 --> 04:00:25,368
DEPARTMENT OF LABOR AND

5663
04:00:25,368 --> 04:00:30,373
DEPARTMENT OF EDUCATION THAT HAS

5664
04:00:30,373 --> 04:00:32,509
COME UP ABOUT LEAVING WORKFORCE

5665
04:00:32,509 --> 04:00:33,276
FOR MANUFACTURING.

5666
04:00:33,276 --> 04:00:35,946
THOSE AGENCIES HAVE PRETTY MUCH

5667
04:00:35,946 --> 04:00:38,248
NOT BEEN VERY INVOLVED.

5668
04:00:38,248 --> 04:00:40,684
I SHOULD ALSO MENTION DEPARTMENT

5669
04:00:40,684 --> 04:00:43,620
OF COMMERCE IN HERE.

5670
04:00:43,620 --> 04:00:47,223
AND MOVING THIS FORWARD.

5671
04:00:47,223 --> 04:00:48,425
OTHERWISE IT BECOMES AN

5672
04:00:48,425 --> 04:00:49,326
INTERESTING IMPORTANT SCIENCE

5673
04:00:49,326 --> 04:00:53,363
PROJECT BUT DOESN'T BECOME AN

5674
04:00:53,363 --> 04:00:55,065
INDUSTRY.

5675
04:00:55,065 --> 04:00:56,099
I ALREADY MENTIONED TRUE TRIALS

5676
04:00:56,099 --> 04:01:02,005
AS A WAY TO FILL A GAP.

5677
04:01:02,005 --> 04:01:03,773
HELPING DEVELOP AND IMPLEMENT

5678
04:01:03,773 --> 04:01:05,742
STANDARDS AND I WILL SAY I

5679
04:01:05,742 --> 04:01:09,346
MENTIONED THOSE TWO SMALL

5680
04:01:09,346 --> 04:01:10,780
ORGANIZATIONS IN PARTICULAR

5681
04:01:10,780 --> 04:01:13,083
BECAUSE THEY ARE EXAMPLES OF FDA

5682
04:01:13,083 --> 04:01:18,455
IN THE WAY THAT FDA CAN WORK

5683
04:01:18,455 --> 04:01:20,190
WITH GROUPS TO MOVE THINGS

5684
04:01:20,190 --> 04:01:20,724
FORWARD.

5685
04:01:20,724 --> 04:01:24,661
AND I THINK AT THE ISSCR

5686
04:01:24,661 --> 04:01:31,701
PRESENTATION THERE WAS A SCREEN 

5687
04:01:31,701 --> 04:01:32,902
SHOT OF THE STANDARDS DOCUMENT

5688
04:01:32,902 --> 04:01:43,346
FDA JUST JUST CAME OUT OF.

5689
04:01:46,416 --> 04:01:48,084
I DIDN'T MENTION ASCR.

5690
04:01:48,084 --> 04:01:49,519
IN TERMS OF SCIENCE AND

5691
04:01:49,519 --> 04:01:53,890
PATIENTS, ONE OF THESE I

5692
04:01:53,890 --> 04:01:56,393
MENTIONED IN THE GENE THERAPY

5693
04:01:56,393 --> 04:01:59,162
CONSORTIUM IS THERE ARE PATIENT

5694
04:01:59,162 --> 04:02:00,697
GROUPS THERE.

5695
04:02:00,697 --> 04:02:04,200
THERE'S THE ORPHAN DISEASES

5696
04:02:04,200 --> 04:02:05,535
THERE, IDENTIFYING PATIENTS

5697
04:02:05,535 --> 04:02:06,836
NEEDS, KNOWING WHERE WE'RE GOING

5698
04:02:06,836 --> 04:02:09,305
TO GO IS REALLY IMPORTANT.

5699
04:02:09,305 --> 04:02:13,376
THOSE WHO SLIDES OF THE SILOS

5700
04:02:13,376 --> 04:02:15,111
THERE, FAIRLY BIG SILOS AND

5701
04:02:15,111 --> 04:02:18,214
STRONG, SITTING IN THE MIDDLE OF

5702
04:02:18,214 --> 04:02:19,616
SOUTH DAKOTA HIGH PLAINS.

5703
04:02:19,616 --> 04:02:21,051
THERE ARE A LITTLE BIT OF

5704
04:02:21,051 --> 04:02:22,819
CONNECTIONS BETWEEN IT.

5705
04:02:22,819 --> 04:02:23,887
THAT'S WHAT HAPPENS HISTORICALLY

5706
04:02:23,887 --> 04:02:29,159
WHEN YOU COME UP WITH BIG

5707
04:02:29,159 --> 04:02:29,592
INITIATIVES.

5708
04:02:29,592 --> 04:02:31,795
THE LOWER PICTURE IS A TYPICAL

5709
04:02:31,795 --> 04:02:33,329
PICTURE OF NEW HAMPSHIRE, IF YOU

5710
04:02:33,329 --> 04:02:35,598
EVER WANT TO COME IN THE FALL.

5711
04:02:35,598 --> 04:02:37,801
THERE'S A PATH THROUGH, LOTS OF

5712
04:02:37,801 --> 04:02:38,268
TREES.

5713
04:02:38,268 --> 04:02:41,071
WHAT ISN'T OBVIOUS FROM THE

5714
04:02:41,071 --> 04:02:43,206
PICTURE IS THE COMMUNICATION

5715
04:02:43,206 --> 04:02:45,742
BETWEEN THE TREES, WHICH HAPPENS

5716
04:02:45,742 --> 04:02:51,915
IN FUNGI AT THE ROOT LEVEL IN

5717
04:02:51,915 --> 04:02:53,249
THE RHISOMES, A LOT HOW MATES

5718
04:02:53,249 --> 04:02:55,552
HAS WORKED OVER THE YEARS.

5719
04:02:55,552 --> 04:02:58,655
A SITUATION WHERE IT DOESN'T GET

5720
04:02:58,655 --> 04:02:59,089
TOP-DOWN.

5721
04:02:59,089 --> 04:03:03,093
IT GETS ACROSS. 

5722
04:03:03,093 --> 04:03:06,396
WE TALKED ABOUT SILOS IN THE

5723
04:03:06,396 --> 04:03:08,898
COMMUNITY WRIT LARGE,

5724
04:03:08,898 --> 04:03:09,799
CREATING -- GETTING

5725
04:03:09,799 --> 04:03:10,266
CROSS-TRAINING.

5726
04:03:10,266 --> 04:03:11,735
THAT'S A REALLY HARD THING TO

5727
04:03:11,735 --> 04:03:13,269
DEVELOP BUT IT'S VERY POWERFUL.

5728
04:03:13,269 --> 04:03:17,006
AND I THINK THAT'S WHERE WE NEED

5729
04:03:17,006 --> 04:03:27,550
TO GO AND TO ENCOURAGE THAT KIND

5730
04:03:28,118 --> 04:03:29,819
OF CROSS-FERTILIZATION, AND GET

5731
04:03:29,819 --> 04:03:30,587
IDEAS WHEN THE CELL-BASED

5732
04:03:30,587 --> 04:03:31,688
THERAPY GETS HERE.

5733
04:03:31,688 --> 04:03:33,990
THANKS. 

5734
04:03:33,990 --> 04:03:36,359
>> THANK YOU VERY MUCH.

5735
04:03:36,359 --> 04:03:42,732
LAST SPEAKER FOR THIS SESSION 

5736
04:03:42,732 --> 04:03:45,969
WILL BE JOSEPHINE LEMBONG.

5737
04:03:45,969 --> 04:03:48,938
 

5738
04:03:48,938 --> 04:03:50,373
>> GOOD AFTERNOON, I'M
SENIOR

5739
04:03:50,373 --> 04:03:53,777
MANAGER OF SCIENCE AND INDUSTRY

5740
04:03:53,777 --> 04:03:55,979
AFFAIRS AT ARM, NOT TO BE

5741
04:03:55,979 --> 04:03:57,680
CONCLUSIONED WITH ARMI, ALLIANCE

5742
04:03:57,680 --> 04:03:59,449
FOR REGENERATIVE MEDICINE.

5743
04:03:59,449 --> 04:04:01,351
WE'RE AN ADVOCACY GROUP,

5744
04:04:01,351 --> 04:04:02,418
SPECIFICALLY ADVOCATING FOR THE

5745
04:04:02,418 --> 04:04:06,256
ADVANCEMENT OF CELL AND GENE

5746
04:04:06,256 --> 04:04:06,523
THERAPIES.

5747
04:04:06,523 --> 04:04:10,860
WE'LL HAVE OVER 350 MEMBER

5748
04:04:10,860 --> 04:04:12,929
COMPANIES GLOBALLY, THAT ARE

5749
04:04:12,929 --> 04:04:18,868
COMPRISED OF DEVELOPERS, PATIENT

5750
04:04:18,868 --> 04:04:19,235
ADVOCACY GROUPS.

5751
04:04:19,235 --> 04:04:21,471
I'LL SAY LIKE MANY OF YOU IN THE

5752
04:04:21,471 --> 04:04:23,173
ROOM WE'VE BEEN THINKING ABOUT

5753
04:04:23,173 --> 04:04:25,642
PLATFORM APPROACHES A LOT.

5754
04:04:25,642 --> 04:04:26,943
SO PLATFORM AS IN LEVERAGING

5755
04:04:26,943 --> 04:04:29,679
DATA OR KNOWLEDGE OUT THERE TO

5756
04:04:29,679 --> 04:04:33,149
BE ABLE TO EXPEDITE DEVELOPMENT

5757
04:04:33,149 --> 04:04:34,551
PROGRAMS WITHIN DEVELOPER OR

5758
04:04:34,551 --> 04:04:35,652
ACROSS DEVELOPERS.

5759
04:04:35,652 --> 04:04:38,922
YOU'LL SEE IN THE TITLE, I USE

5760
04:04:38,922 --> 04:04:41,424
THE TERM BUILDING BLOCKS INSTEAD

5761
04:04:41,424 --> 04:04:42,759
OF PLATFORMS, A TECHNICAL TERM I

5762
04:04:42,759 --> 04:04:45,762
REALIZE BUT FOR A REASON I'LL

5763
04:04:45,762 --> 04:04:50,500
SHOW IN A COUPLE SLIDES.

5764
04:04:50,500 --> 04:04:53,636
SO, WE JUST FINISHED A MEETING

5765
04:04:53,636 --> 04:04:55,171
LAST WEEK WHICH WE CALL

5766
04:04:55,171 --> 04:04:55,605
SCIENTIFIC EXCHANGE.

5767
04:04:55,605 --> 04:04:59,475
THIS IS A NEW FORMAT OF

5768
04:04:59,475 --> 04:05:01,811
INTERACTION THAT WE CONVENE

5769
04:05:01,811 --> 04:05:03,012
AMONG OUR DEVELOPERS, MEMBERSHIP

5770
04:05:03,012 --> 04:05:03,746
AND FDA.

5771
04:05:03,746 --> 04:05:05,615
AND THE TOPIC OF THAT

5772
04:05:05,615 --> 04:05:07,483
INTERACTION THIS YEAR IS

5773
04:05:07,483 --> 04:05:09,652
UNLOCKING THE POTENTIAL OF

5774
04:05:09,652 --> 04:05:12,856
BUILDING BLOCKS TO EXPEDITE GENE

5775
04:05:12,856 --> 04:05:14,157
THERAPY DEVELOPMENT AND REVIEW.

5776
04:05:14,157 --> 04:05:15,792
YOU SHOULD ALWAYS START WITH

5777
04:05:15,792 --> 04:05:18,094
DEFINITIONS, BUILDING BLOCK IS

5778
04:05:18,094 --> 04:05:19,295
COMPONENT OF DEVELOPMENT PROGRAM

5779
04:05:19,295 --> 04:05:22,332
THAT CAN BE REUSED IN OTHER

5780
04:05:22,332 --> 04:05:24,100
PROGRAMS, EITHER BY THE ORIGINAL

5781
04:05:24,100 --> 04:05:26,836
DEVELOPER OR POTENTIALLY BY

5782
04:05:26,836 --> 04:05:28,204
OTHER DEVELOPERS AND STREAMLINE

5783
04:05:28,204 --> 04:05:30,106
NECESSARY EFFORTS TO VALIDATE

5784
04:05:30,106 --> 04:05:31,574
THE COMPONENT.

5785
04:05:31,574 --> 04:05:35,478
THE OBJECTIVE OF THE BUILDING 

5786
04:05:35,478 --> 04:05:37,046
BLOCK TO IMPROVE TIME AND

5787
04:05:37,046 --> 04:05:40,316
RESOURCE SUFFICIENCY OF

5788
04:05:40,316 --> 04:05:41,551
DEVELOPMENT AND REGULATORY

5789
04:05:41,551 --> 04:05:42,719
REVIEW BY LEVERAGING ACROSS

5790
04:05:42,719 --> 04:05:44,587
PROGRAMS, ALSO TO MAKE VIABLE

5791
04:05:44,587 --> 04:05:46,456
PURSUIT OF ADDITIONAL RARE

5792
04:05:46,456 --> 04:05:47,657
DISEASE TARGETS.

5793
04:05:47,657 --> 04:05:49,826
SO WE ACKNOWLEDGE THAT BUILDING

5794
04:05:49,826 --> 04:05:51,060
BLOCKS CAN TAKE MULTIPLE FORMS,

5795
04:05:51,060 --> 04:05:53,463
SO IF YOU LOOK IN THE BOTTOM

5796
04:05:53,463 --> 04:05:57,667
LEFT, THE FIRST BULLET POINT IS

5797
04:05:57,667 --> 04:05:59,702
THE DESIGNATED TECHNOLOGY

5798
04:05:59,702 --> 04:06:01,804
PLATFORM, SO THERE'S A REASON

5799
04:06:01,804 --> 04:06:04,440
AMONG ITS PROVISIONS CALLS THE

5800
04:06:04,440 --> 04:06:06,075
FDA TO DESIGNATE PLATFORM

5801
04:06:06,075 --> 04:06:07,176
TECHNOLOGIES, AND THESE

5802
04:06:07,176 --> 04:06:08,177
PLATFORMS ARE ESSENTIALLY

5803
04:06:08,177 --> 04:06:10,346
ELEMENTS OF A DEVELOPMENT AGAIN

5804
04:06:10,346 --> 04:06:12,415
THAT CAN BE LEVERAGED ACROSS

5805
04:06:12,415 --> 04:06:14,017
DEVELOPERS, MUST BE ATTACHED TO

5806
04:06:14,017 --> 04:06:15,585
A BLA.

5807
04:06:15,585 --> 04:06:19,555
I THINK THE FDA IS SCHEDULED

5808
04:06:19,555 --> 04:06:23,660
TO -- HAS TO PUBLISH GUIDANCE

5809
04:06:23,660 --> 04:06:25,828
FOR THE YEAR, IT WILL BE

5810
04:06:25,828 --> 04:06:30,166
INTERESTING TO SEE WHAT KIND OF

5811
04:06:30,166 --> 04:06:31,367
THE RESTRICTIONS AROUND THIS

5812
04:06:31,367 --> 04:06:32,802
DESIGNATION PLATFORM IS.

5813
04:06:32,802 --> 04:06:34,437
THERE'S ALSO ALWAYS PRIOR

5814
04:06:34,437 --> 04:06:35,405
KNOWLEDGE.

5815
04:06:35,405 --> 04:06:36,739
WITHIN A DEVELOPER, A MECHANISM

5816
04:06:36,739 --> 04:06:37,907
A DEVELOPER CAN LEVERAGE RIGHT

5817
04:06:37,907 --> 04:06:40,109
NOW DURING THEIR INTERACTION

5818
04:06:40,109 --> 04:06:45,682
WITH THE FDA, ACROSS THEIR 

5819
04:06:45,682 --> 04:06:46,883
INTERNAL PROGRAMS.

5820
04:06:46,883 --> 04:06:49,552
I ALSO MENTION MASTER FILES AS

5821
04:06:49,552 --> 04:06:50,286
POTENTIAL PLATFORM.

5822
04:06:50,286 --> 04:06:52,588
WE TALKED ABOUT CELL BANKS, A

5823
04:06:52,588 --> 04:06:55,625
COMMON PLATFORM DEVELOPERS HAVE

5824
04:06:55,625 --> 04:06:57,627
BEEN SUCCESSFULLY USING WITHIN

5825
04:06:57,627 --> 04:06:59,395
THEIR PROGRAMS.

5826
04:06:59,395 --> 04:07:02,632
SO, THESE ARE JUST TOOLS. 

5827
04:07:02,632 --> 04:07:04,167
WE DON'T WANT TO LIMIT -- IT'S

5828
04:07:04,167 --> 04:07:11,007
WHY WE USE THE TERM BUILDING

5829
04:07:11,007 --> 04:07:12,842
BLOCKS, THE PLATFORM AS LANGUAGE

5830
04:07:12,842 --> 04:07:15,345
IS LIMITED TO USE OF ELEMENT OF

5831
04:07:15,345 --> 04:07:16,546
TECHNOLOGY ATTACHED TO BLA,

5832
04:07:16,546 --> 04:07:18,314
ORIGINAL DEVELOPER.

5833
04:07:18,314 --> 04:07:20,817
SO THIS MEETING WE HELD ON

5834
04:07:20,817 --> 04:07:22,018
NOVEMBER 1, JUST LAST WEEK,

5835
04:07:22,018 --> 04:07:23,319
YOU'RE THE FIRST GROUP TO HEAR

5836
04:07:23,319 --> 04:07:31,094
THE OUTCOME OF THIS MEETING, WE

5837
04:07:31,094 --> 04:07:33,596
PRESENTED CASE STUDIES AROUND

5838
04:07:33,596 --> 04:07:36,132
KEY TECHNOLOGY AREAS, ANY OF

5839
04:07:36,132 --> 04:07:43,706
THESE iPSCs AS WELL AS LNP,

5840
04:07:43,706 --> 04:07:46,209
REPRESENTATIVES FROM THE FDA

5841
04:07:46,209 --> 04:07:47,944
FROM THE DIFFERENT BRANCHES, AND

5842
04:07:47,944 --> 04:07:51,781
IT'S REALLY JUST TO DISCUSS THE

5843
04:07:51,781 --> 04:07:53,449
PRINCIPLES AROUND THE SELECTION,

5844
04:07:53,449 --> 04:07:54,751
WHAT COULD BE LEVERAGED AS A

5845
04:07:54,751 --> 04:07:57,587
PLATFORM IN A PROGRAM AND HOW DO

5846
04:07:57,587 --> 04:07:59,088
YOU IMPLEMENT THAT PLATFORM IN

5847
04:07:59,088 --> 04:08:00,556
YOUR INTERNAL PROGRAM OR OTHER

5848
04:08:00,556 --> 04:08:01,624
DEVELOPMENT PROGRAMS.

5849
04:08:01,624 --> 04:08:03,526
AND THE OBJECTIVE IS NOT REALLY

5850
04:08:03,526 --> 04:08:05,695
TO, YOU KNOW, SAY YES OR NO TO

5851
04:08:05,695 --> 04:08:08,498
WHAT IS A VIABLE PLATFORM

5852
04:08:08,498 --> 04:08:10,967
BETWEEN THE OPTIONS THAT ARE

5853
04:08:10,967 --> 04:08:12,502
PRESENTED BY DEVELOPERS, BUT

5854
04:08:12,502 --> 04:08:14,670
REALLY TO IDENTIFY THE PATH TO

5855
04:08:14,670 --> 04:08:16,205
FURTHER REFINE THE MOST

5856
04:08:16,205 --> 04:08:17,840
PROMISING BUILDING BLOCKS

5857
04:08:17,840 --> 04:08:19,909
PROVIDED BY THE DEVELOPER AND

5858
04:08:19,909 --> 04:08:22,879
SHED A LIGHT HOW THEY CAN BE

5859
04:08:22,879 --> 04:08:26,716
DEVELOPED, VALIDATED, DEPLOYED.

5860
04:08:26,716 --> 04:08:28,551
SOMEONE INTRODUCED THE FRAMEWORK

5861
04:08:28,551 --> 04:08:29,986
OF THE MEETING, WE WANT TO

5862
04:08:29,986 --> 04:08:31,954
PRESENT WHAT IS THE BUILDING

5863
04:08:31,954 --> 04:08:33,790
BLOCK, A CELL BANK, A TEST, IS

5864
04:08:33,790 --> 04:08:35,224
IT A PROCESS?

5865
04:08:35,224 --> 04:08:36,893
HOW IS IT CHARACTERIZED?

5866
04:08:36,893 --> 04:08:37,660
WHAT IS THE RIGHT

5867
04:08:37,660 --> 04:08:38,628
CHARACTERIZATION TO BE ABLE

5868
04:08:38,628 --> 04:08:41,597
TO -- FOR IT TO BE IMPLEMENTED?

5869
04:08:41,597 --> 04:08:45,868
WHO CAN REFERENCE AND WHAT

5870
04:08:45,868 --> 04:08:48,571
BASIS, AS WELL AS WHAT RESOURCE

5871
04:08:48,571 --> 04:08:50,273
SAVINGS DOES IT BRING TO THE

5872
04:08:50,273 --> 04:08:51,374
ORIGINAL DEVELOPER OR LICENSING?

5873
04:08:51,374 --> 04:08:54,444
THIS IS MAYBE A BIT OF A BUSY

5874
04:08:54,444 --> 04:08:58,581
SLIDE BUT IF YOU LOOK AT THE

5875
04:08:58,581 --> 04:08:59,248
BOTTOM THERE'S DESIGNATED

5876
04:08:59,248 --> 04:09:00,216
TECHNOLOGY PLATFORM AND WE LOOK

5877
04:09:00,216 --> 04:09:02,318
AT THE COLUMNS, WHO DEVELOPS IT,

5878
04:09:02,318 --> 04:09:04,887
WHAT IS NEEDED FOR IT TO BE

5879
04:09:04,887 --> 04:09:07,690
USED, AND WHAT IS THE VEHICLE OF

5880
04:09:07,690 --> 04:09:09,659
DISSEMINATION IN THE FIELD.

5881
04:09:09,659 --> 04:09:11,394
TECHNOLOGY PLATFORM IS NARROW,

5882
04:09:11,394 --> 04:09:13,496
WHY WE DIDN'T WANT TO FOCUS AT

5883
04:09:13,496 --> 04:09:14,797
THE MEETING ITSELF.

5884
04:09:14,797 --> 04:09:17,667
IT'S DEVELOPED BY THE MEDICINE

5885
04:09:17,667 --> 04:09:19,602
SPONSOR AND HAS TO BE TIED A BLA

5886
04:09:19,602 --> 04:09:22,271
SO IT'S TIED TO AN APPROVED DRUG

5887
04:09:22,271 --> 04:09:25,475
AND IT'S AN OFFICIAL STAND FROM

5888
04:09:25,475 --> 04:09:26,075
THE FDA, FDA-DESIGNATED

5889
04:09:26,075 --> 04:09:26,709
PLATFORM.

5890
04:09:26,709 --> 04:09:31,781
IT CAN BE USED FOR DEVELOPER 

5891
04:09:31,781 --> 04:09:33,082
ITSELF OR OTHER DEVELOPER

5892
04:09:33,082 --> 04:09:34,317
LICENSING THE TECHNOLOGY.

5893
04:09:34,317 --> 04:09:35,651
PRIOR KNOWLEDGE IS A BROADER

5894
04:09:35,651 --> 04:09:35,818
BOX.

5895
04:09:35,818 --> 04:09:38,488
AS WE GET TO BROADER PROCESS

5896
04:09:38,488 --> 04:09:42,892
WE'RE TALKING ABOUT SECTOR-WIDE

5897
04:09:42,892 --> 04:09:43,860
EFFORTS, COALITIONS, CONSORTIUM

5898
04:09:43,860 --> 04:09:46,696
WHICH EVERYONE IS INTERESTED IN

5899
04:09:46,696 --> 04:09:50,766
AND WHAT CAN THAT DISSEMINATION

5900
04:09:50,766 --> 04:09:54,570
LOOK LIKE, WHO IS LEVERAGE AND

5901
04:09:54,570 --> 04:09:56,873
BENEFIT FROM THERE.

5902
04:09:56,873 --> 04:09:58,741
SO I THINK, AGAIN, WE REALIZE

5903
04:09:58,741 --> 04:10:00,376
THE BUILDING BLOCK CAN COME IN

5904
04:10:00,376 --> 04:10:01,410
MANY FORMS.

5905
04:10:01,410 --> 04:10:03,346
WE MUST BE NIMBLE IN HOW THIS

5906
04:10:03,346 --> 04:10:04,213
TOPIC IS EXPLORED.

5907
04:10:04,213 --> 04:10:08,985
IT CAN BE A SLATE OF TESTS TO

5908
04:10:08,985 --> 04:10:10,486
CHARACTERIZE A PRODUCT, SERIES

5909
04:10:10,486 --> 04:10:12,889
OF QAs ATTACHED TO A DRUG, CAN

5910
04:10:12,889 --> 04:10:15,391
BE A MANUFACTURING PROCESS

5911
04:10:15,391 --> 04:10:18,127
THAT'S PRESENTED BY SOME

5912
04:10:18,127 --> 04:10:19,228
DEVELOPERS, AND I THINK WE HAVE

5913
04:10:19,228 --> 04:10:20,997
KNOWLEDGE THAT SOME OF THESE

5914
04:10:20,997 --> 04:10:22,932
BUILDING BLOCKS WITH EASIER TO

5915
04:10:22,932 --> 04:10:26,435
DEPLOY AND BUILD BY A SINGLE

5916
04:10:26,435 --> 04:10:28,204
DEVELOPER VERSUS A COMPETITIVE

5917
04:10:28,204 --> 04:10:29,172
EFFORT, DIFFICULT TO ADVANCE

5918
04:10:29,172 --> 04:10:30,606
ACROSS DEVELOPERS, CAN BE LINKED

5919
04:10:30,606 --> 04:10:33,776
TO A COMPANY'S MANUFACTURING

5920
04:10:33,776 --> 04:10:36,979
PROCESS,  PROPRIETARY AND

5921
04:10:36,979 --> 04:10:37,547
LIMITING BENEFITS.

5922
04:10:37,547 --> 04:10:39,348
I WANT TO PRESENT FOUR KEY

5923
04:10:39,348 --> 04:10:40,783
THEMES THAT EMERGED FROM THE

5924
04:10:40,783 --> 04:10:42,552
MEETING, WHAT A VIABLE BUILDING

5925
04:10:42,552 --> 04:10:45,388
BLOCK CAN LOOK LIKE.

5926
04:10:45,388 --> 04:10:48,524
CELL BANKS WITH A SET OF TESTS

5927
04:10:48,524 --> 04:10:50,993
AND SPECIFICATIONS, CELL BANKS

5928
04:10:50,993 --> 04:10:56,532
TESTING THAT INCLUDES GENOMIC

5929
04:10:56,532 --> 04:10:58,067
STABILITY AND INNOVATION OVER

5930
04:10:58,067 --> 04:10:58,868
TIME.

5931
04:10:58,868 --> 04:10:59,802
WHAT IS LEVEL OF GENETIC

5932
04:10:59,802 --> 04:11:00,703
IDENTITY FOR COMMERCIAL PRODUCTS

5933
04:11:00,703 --> 04:11:02,605
BROUGHT TO THE INDUSTRY?

5934
04:11:02,605 --> 04:11:04,907
AND, YOU KNOW, THE TEAM IN THAT

5935
04:11:04,907 --> 04:11:07,276
ROOM DURING THAT MEETING HAS

5936
04:11:07,276 --> 04:11:08,477
EXPRESSED INTEREST IN

5937
04:11:08,477 --> 04:11:09,779
ESTABLISHING AN INDUSTRY

5938
04:11:09,779 --> 04:11:12,715
CONSENSUS, WHAT THE PROPER

5939
04:11:12,715 --> 04:11:14,917
CHARACTERIZATION OF AN iPSC

5940
04:11:14,917 --> 04:11:15,618
CELL BANK IS.

5941
04:11:15,618 --> 04:11:18,654
THERE ARE LIMITATIONS ON

5942
04:11:18,654 --> 04:11:19,655
VARIABILITY OF CELLULAR MATERIAL

5943
04:11:19,655 --> 04:11:22,458
AND IF IT IS EDITED WE MUST PICK

5944
04:11:22,458 --> 04:11:23,492
THE BEST CLONE TO ELIMINATE

5945
04:11:23,492 --> 04:11:32,134
VARIANCE YEAH BIT AND WHAT IS 

5946
04:11:32,134 --> 04:11:33,102
THE -- VARIABILITY.

5947
04:11:33,102 --> 04:11:35,004
THE CHANNEL OR LIMITATION WE

5948
04:11:35,004 --> 04:11:37,473
NEED AN IN VIVO/IN VITRO

5949
04:11:37,473 --> 04:11:40,643
CORRELATION ACROSS MULTIPLE

5950
04:11:40,643 --> 04:11:41,377
PRODUCTS UNDERSTANDING

5951
04:11:41,377 --> 04:11:42,011
TRANSLATABILITY AND VALIDATION

5952
04:11:42,011 --> 04:11:44,380
OF METHODS AND NEED FOR

5953
04:11:44,380 --> 04:11:44,880
REFERENCE STANDARDS.

5954
04:11:44,880 --> 04:11:50,353
THERE'S A LOT OF DISCUSSION

5955
04:11:50,353 --> 04:11:51,587
AROUND PLATFORM PROCESS, COULD

5956
04:11:51,587 --> 04:11:57,193
BE RELATED TO A SINGLE UNIT, AND

5957
04:11:57,193 --> 04:12:00,596
CHARACTERIZATION THAT IS NEEDED

5958
04:12:00,596 --> 04:12:04,533
IS THE ASSOCIATED CPPs,

5959
04:12:04,533 --> 04:12:07,036
OPERATING RANGES, EXPECTED

5960
04:12:07,036 --> 04:12:08,804
OUTPUT, CRITICAL QUALITY

5961
04:12:08,804 --> 04:12:13,943
ATTRIBUTES FOR CELLULAR

5962
04:12:13,943 --> 04:12:17,446
THERAPIES, BROUGHT UP MANY

5963
04:12:17,446 --> 04:12:17,680
TIMES.

5964
04:12:17,680 --> 04:12:19,749
ONE OPERATION TO THE OTHER, ONE

5965
04:12:19,749 --> 04:12:21,817
SERIES OF UNIT OPERATIONS,

5966
04:12:21,817 --> 04:12:23,919
CALLED THE PLATFORM, TO ANOTHER

5967
04:12:23,919 --> 04:12:25,888
PROCESS IS VERY CRITICAL.

5968
04:12:25,888 --> 04:12:28,624
AND THE LAST BUT NOT LEAST, GENE

5969
04:12:28,624 --> 04:12:30,926
EDITING PLATFORM IS BROUGHT UP

5970
04:12:30,926 --> 04:12:32,461
AS A POTENTIAL VIABLE BUILDING

5971
04:12:32,461 --> 04:12:34,196
BLOCK AS WELL.

5972
04:12:34,196 --> 04:12:37,700
SO THE LNP AND MANUFACTURING

5973
04:12:37,700 --> 04:12:39,669
PLATFORM WITH SWAPPABLE GUIDE

5974
04:12:39,669 --> 04:12:40,102
RNA.

5975
04:12:40,102 --> 04:12:45,141
AND UNDERSTANDING AGAIN THE

5976
04:12:45,141 --> 04:12:45,808
LIMITATIONS, UNDERSTANDING

5977
04:12:45,808 --> 04:12:47,243
OFF-TARGET EFFECTS FROM PRODUCT

5978
04:12:47,243 --> 04:12:48,811
TO PRODUCT IS CRITICAL.

5979
04:12:48,811 --> 04:12:50,513
ONE WAY TO MAKE A VIABLE

5980
04:12:50,513 --> 04:12:52,048
DEVELOPMENT FOR SMALLER

5981
04:12:52,048 --> 04:12:53,249
POPULATION TO HAVE A COMMON

5982
04:12:53,249 --> 04:13:00,623
SUPPLY OF CLINICAL TRIAL 

5983
04:13:00,623 --> 04:13:01,724
REAGENTS PRODUCT AGNOSTIC

5984
04:13:01,724 --> 04:13:02,792
STREAMLINED ONCE THE INITIAL

5985
04:13:02,792 --> 04:13:03,693
QUALIFICATION WAS DONE.

5986
04:13:03,693 --> 04:13:05,227
I'M STANDING BETWEEN YOU AND

5987
04:13:05,227 --> 04:13:06,395
LUNCH, I'LL END THERE.

5988
04:13:06,395 --> 04:13:07,730
HAPPY TO STICK AROUND FOR

5989
04:13:07,730 --> 04:13:08,097
QUESTIONS.

5990
04:13:08,097 --> 04:13:14,170
THANK YOU. 

5991
04:13:14,170 --> 04:13:14,503
>> ALL RIGHT.

5992
04:13:14,503 --> 04:13:15,705
THANK YOU VERY MUCH.

5993
04:13:15,705 --> 04:13:17,273
WITH THAT, WE'RE GOING TO CLOSE

5994
04:13:17,273 --> 04:13:18,140
THIS SESSION.

5995
04:13:18,140 --> 04:13:19,642
UNFORTUNATELY WE DON'T HAVE TIME

5996
04:13:19,642 --> 04:13:20,943
FOR DISCUSSION THIS SESSION BUT

5997
04:13:20,943 --> 04:13:23,045
I THINK THOSE WERE ALL GREAT

5998
04:13:23,045 --> 04:13:23,279
THANKS.

5999
04:13:23,279 --> 04:13:24,380
THANKS FOR SHARING YOUR IDEAS.

6000
04:13:24,380 --> 04:13:25,481
WE CAN INCORPORATE THOSE INTO

6001
04:13:25,481 --> 04:13:28,517
THE REST OF OUR DISCUSSIONS AS
WE CONTINUE THIS MEETING.

6002
04:13:28,517 --> 04:13:30,784


6003
04:13:30,784 --> 04:13:33,687
IT'S TIME TO GET BACK TO WORK 

6004
04:13:33,687 --> 04:13:37,791
WITH THE WORKING LUNCH.

6005
04:13:37,791 --> 04:13:42,929
WE'RE NOT GOING TO DO AN 

6006
04:13:42,929 --> 04:13:44,898
INTRODUCTION BUT REALLY THANK

6007
04:13:44,898 --> 04:13:46,433
YOU FOR JOINING US.

6008
04:13:46,433 --> 04:13:48,535
THIS REQUEST GOT PASSED DOWN

6009
04:13:48,535 --> 04:13:49,369
SEVERAL TIMES.

6010
04:13:49,369 --> 04:13:51,271
SCOTT STEELE WAS INVOLVED IN

6011
04:13:51,271 --> 04:13:53,106
HELPING PLAN THIS, REALLY WAS

6012
04:13:53,106 --> 04:13:58,378
INVALUABLE. 

6013
04:13:58,378 --> 04:14:00,347
BUT HE WAS TRAVELING, AND SO DR.

6014
04:14:00,347 --> 04:14:01,982
EKKO AGREED TO STEP IN.

6015
04:14:01,982 --> 04:14:03,984
HOPE YOU ENJOYED THE SESSION,

6016
04:14:03,984 --> 04:14:05,952
LOOK FORWARD TO HEARING THE FDA

6017
04:14:05,952 --> 04:14:08,488
PERSPECTIVE THOUSAND MOVE THE

6018
04:14:08,488 --> 04:14:09,122
FIELD FORWARD PARTICULARLY HOW

6019
04:14:09,122 --> 04:14:12,526
WE CAN DO IT COLLECTIVELY. 

6020
04:14:12,526 --> 04:14:22,769
SO THANK YOU. 

6021
04:14:23,503 --> 04:14:26,740
>> GOOD AFTERNOON. 

6022
04:14:26,740 --> 04:14:30,911
I'M THE DIVISION DIRECTOR FOR A

6023
04:14:30,911 --> 04:14:33,413
CHEMISTRY MANUFACTURING

6024
04:14:33,413 --> 04:14:37,050
CLINICAL -- - CHEMISTRY

6025
04:14:37,050 --> 04:14:39,419
MANUFACTURING DIVISION WITHIN

6026
04:14:39,419 --> 04:14:40,420
OUR NEWLY FORMED REORGANIZED

6027
04:14:40,420 --> 04:14:47,027
OFFICE OF THERAPEUTIC PRODUCTS.

6028
04:14:47,027 --> 04:14:47,794
I THINK MY PRESENTATION, YOU'VE

6029
04:14:47,794 --> 04:14:49,229
COVERED ALL OF IDENTIFY DURING

6030
04:14:49,229 --> 04:14:53,600
TODAY'S TALKS SO FAR.

6031
04:14:53,600 --> 04:14:56,636
HOPEFULLY THERE WILL BE FOOD FOR

6032
04:14:56,636 --> 04:14:58,738
THOUGHT WHILE YOU'RE ENJOYING

6033
04:14:58,738 --> 04:15:05,645
YOUR LUNCH. 

6034
04:15:05,645 --> 04:15:16,122
I DON'T THINK IT'S WORKING. 

6035
04:15:17,924 --> 04:15:19,526
CAN'T SEEM TO ADVANCE MY SLIDES.

6036
04:15:19,526 --> 04:15:24,030
SO BEFORE I DELVE INTO SOME

6037
04:15:24,030 --> 04:15:26,399
ISSUES WE FREQUENTLY ENCOUNTER

6038
04:15:26,399 --> 04:15:30,237
AT FDA, FOR CELL THERAPY

6039
04:15:30,237 --> 04:15:33,507
PRODUCTS, I WANTED TO TOUCH UPON

6040
04:15:33,507 --> 04:15:34,841
THE NEW STRUCTURE, ONE OF THE

6041
04:15:34,841 --> 04:15:40,447
FIRST CHALLENGES I WILL DISCUSS

6042
04:15:40,447 --> 04:15:42,282
THAT WE ENCOUNTER.

6043
04:15:42,282 --> 04:15:48,955
THIS IS A QUICK OVERVIEW OF THE

6044
04:15:48,955 --> 04:15:49,789
CBER STRUCTURE, A SUPER OFFICE

6045
04:15:49,789 --> 04:15:51,124
FORMED THIS YEAR.

6046
04:15:51,124 --> 04:15:52,459
OFFICE OF THERAPEUTIC PRODUCTS

6047
04:15:52,459 --> 04:15:55,829
WAS PREVIOUSLY OFFICE OF TISSUE

6048
04:15:55,829 --> 04:16:03,603
AND ADVANCED THERAPIES.

6049
04:16:03,603 --> 04:16:05,572
OTAT TRANSITIONED INTO A SUPER

6050
04:16:05,572 --> 04:16:09,209
OFFICE THIS PAST FEBRUARY, NOW

6051
04:16:09,209 --> 04:16:13,780
CONSISTS OF SIX SUBOFFICES TO 

6052
04:16:13,780 --> 04:16:16,983
HELP BETTER MANAGE THE GROWING

6053
04:16:16,983 --> 04:16:20,453
FIELD THAT YOU GUYS CALL -- THE

6054
04:16:20,453 --> 04:16:21,788
RAPIDLY GROWING FIELD YOU'VE

6055
04:16:21,788 --> 04:16:22,322
TOUCHED UPON.

6056
04:16:22,322 --> 04:16:24,090
THE OFFICE OF GENE THERAPY AND

6057
04:16:24,090 --> 04:16:27,060
OFFICE OF CELL THERAPY AND HUMAN

6058
04:16:27,060 --> 04:16:29,563
TISSUE FOR OCTHT WHERE I SIT,

6059
04:16:29,563 --> 04:16:32,532
HIGHLIGHTED HERE, WE USED TO BE

6060
04:16:32,532 --> 04:16:33,500
ACTUALLY JUST ONE DIVISION,

6061
04:16:33,500 --> 04:16:40,840
DIVISION OF CELL AND GENE

6062
04:16:40,840 --> 04:16:43,443
THERAPY, DCGT, WE'RE RESPONSIBLE

6063
04:16:43,443 --> 04:16:44,911
FOR CHEMISTRY MANUFACTURING

6064
04:16:44,911 --> 04:16:46,179
CONTROLS FOR CELL AND GENE

6065
04:16:46,179 --> 04:16:47,647
THERAPY PRODUCTS.

6066
04:16:47,647 --> 04:16:54,821
LIKE I MENTIONED

6067
04:16:54,821 --> 04:16:56,022
THERE ARE ADDITIONAL SUBOFFICES,

6068
04:16:56,022 --> 04:16:57,257
OFFICE OF CLINICAL EVALUATION

6069
04:16:57,257 --> 04:17:01,728
AND OFFICE OF PHARMACOLOGY AND

6070
04:17:01,728 --> 04:17:06,733
TOXICOLOGY, WHICH THE PT OFFICE

6071
04:17:06,733 --> 04:17:07,400
REVIEWS MAINLY PRE-CLINICAL

6072
04:17:07,400 --> 04:17:12,005
STUDIES, AND THAT USED TO BE 

6073
04:17:12,005 --> 04:17:13,206
ACTUALLY A SINGLE DIVISION,

6074
04:17:13,206 --> 04:17:15,809
BECAUSE OF THE GROWTH THOUGH WE

6075
04:17:15,809 --> 04:17:18,979
NOW FORMED INTO THIS LARGER

6076
04:17:18,979 --> 04:17:28,755
SUPER OFFICE, WITH SUBOFFICES

6077
04:17:28,755 --> 04:17:28,989
WITHIN.

6078
04:17:28,989 --> 04:17:30,523
WHAT'S HIGHLIGHTED HERE IS THE

6079
04:17:30,523 --> 04:17:34,794
TOP RECTANGLE IS OUR NEW

6080
04:17:34,794 --> 04:17:36,229
SUPERSTRUCTURE OFFICE, OTP.

6081
04:17:36,229 --> 04:17:38,865
AND THEN THE SUBOFFICES BELOW IT

6082
04:17:38,865 --> 04:17:40,500
IN RECTANGLES.

6083
04:17:40,500 --> 04:17:42,636
SO YOU CAN SEE JUST HOW FAR

6084
04:17:42,636 --> 04:17:51,111
WE'VE GONE OVER THE YEARS, AND

6085
04:17:51,111 --> 04:17:53,947
WITHIN EACH RECTANGLE YOU'LL SEE

6086
04:17:53,947 --> 04:17:57,784
LINES UNDERNEATH IT, THOSE ARE

6087
04:17:57,784 --> 04:17:59,953
ACTUALLY BRANCHES.

6088
04:17:59,953 --> 04:18:01,388
WE'VE REALLY JUST GROWN

6089
04:18:01,388 --> 04:18:04,257
EXPONENTIALLY OVER THE YEARS AND

6090
04:18:04,257 --> 04:18:07,560
THIS IS STILL JUST CATCHING UP.

6091
04:18:07,560 --> 04:18:11,698
SOMEONE MENTIONED EARLIER IN THE

6092
04:18:11,698 --> 04:18:12,465
TALKS TODAY.

6093
04:18:12,465 --> 04:18:15,068
I'VE BEEN WITH THE CELL THERAPY

6094
04:18:15,068 --> 04:18:17,971
BRANCH FOR THE LAST FIVE YEARS,

6095
04:18:17,971 --> 04:18:20,273
AS A BRANCH CHIEF, AND WE'VE

6096
04:18:20,273 --> 04:18:23,410
GROWN FROM A SINGLE BRANCH

6097
04:18:23,410 --> 04:18:30,216
WITHIN A DIVISION FOR CMC -- I

6098
04:18:30,216 --> 04:18:32,485
HAVE TO COUNT.

6099
04:18:32,485 --> 04:18:34,754
THERE'S AT LEAST FOUR DIFFERENT

6100
04:18:34,754 --> 04:18:37,757
BRANCHES THAT WE'VE BROKEN UP

6101
04:18:37,757 --> 04:18:39,859
INTO FROM ONE BRANCH SO YOU CAN

6102
04:18:39,859 --> 04:18:40,860
IMAGINE HOW MUCH WE'VE GROWN

6103
04:18:40,860 --> 04:18:43,129
EVEN JUST IN THE LAST FIVE YEARS

6104
04:18:43,129 --> 04:18:49,736
AND JUST THIS PAST FEBRUARY.

6105
04:18:49,736 --> 04:18:51,671
AS YOU'RE ALL AWARE THE

6106
04:18:51,671 --> 04:18:54,841
DIVERSITY OF PRODUCTS WE REVIEW,

6107
04:18:54,841 --> 04:19:00,613
AND OTP IS WIDE, WE REVIEW STEM

6108
04:19:00,613 --> 04:19:10,724
CELLS, iPSC PRODUCTS, WE HAVE

6109
04:19:10,724 --> 04:19:11,257
XENOTRANSPLANTATION, ALSO

6110
04:19:11,257 --> 04:19:11,925
CELL-BASED IMMUNOTHERAPY

6111
04:19:11,925 --> 04:19:13,760
PRODUCTS FALL INTO MY DIVISION.

6112
04:19:13,760 --> 04:19:15,862
WE ALSO REVIEW CELL THERAPY

6113
04:19:15,862 --> 04:19:18,131
PRODUCTS THAT ARE -- I SHOULD

6114
04:19:18,131 --> 04:19:21,000
SAY JUST A DIFFERENTIATE FROM

6115
04:19:21,000 --> 04:19:25,138
OJT, WE REVIEW PRODUCTS THAT ARE

6116
04:19:25,138 --> 04:19:26,039
NOT GENETICALLY MODIFIED,

6117
04:19:26,039 --> 04:19:28,575
ALTHOUGH THERE ARE SOME ITEMS

6118
04:19:28,575 --> 04:19:29,309
LIKE XENOTRANSPLANTATION WHERE

6119
04:19:29,309 --> 04:19:33,446
YOU'RE GOING TO HAVE TO

6120
04:19:33,446 --> 04:19:34,781
MEDICALLY MODIFY ANIMALS THAT

6121
04:19:34,781 --> 04:19:37,450
THE FINAL ORGANS FALL INTO

6122
04:19:37,450 --> 04:19:41,354
OUR -- INTO MY DIVISION. 

6123
04:19:41,354 --> 04:19:44,457
SO THERE'S SOME CROSSOVERS AND

6124
04:19:44,457 --> 04:19:45,959
MEANT MODIFICATION WITH

6125
04:19:45,959 --> 04:19:48,061
iPSCs AS WELL.

6126
04:19:48,061 --> 04:19:49,596
THIS ILLUSTRATES THE DIVERSITY

6127
04:19:49,596 --> 04:19:52,065
OF THE PRODUCTS WE HAVE TO BE ON

6128
04:19:52,065 --> 04:19:57,904
TOP OF WITHIN OUR SMALL OFFICES,

6129
04:19:57,904 --> 04:20:02,609
GROWING OFFICE, I SHOULD SAY. 

6130
04:20:02,609 --> 04:20:04,377
SO, AS I MENTIONED, THE FIRST

6131
04:20:04,377 --> 04:20:07,647
CHALLENGE THAT I WANTED TO BRING

6132
04:20:07,647 --> 04:20:10,383
UP IS JUST HIGHLIGHTING AND

6133
04:20:10,383 --> 04:20:11,384
ACKNOWLEDGING THE RAPIDLY

6134
04:20:11,384 --> 04:20:12,585
GROWING FIELD.

6135
04:20:12,585 --> 04:20:15,655
AND ALL OF THE CONCERNS THAT

6136
04:20:15,655 --> 04:20:20,059
COMES WITH KEEPING UP WITH THE

6137
04:20:20,059 --> 04:20:20,827
GROWING FIELD.

6138
04:20:20,827 --> 04:20:23,830
AND THIS IS ILLUSTRATED BY THE

6139
04:20:23,830 --> 04:20:25,165
RAPIDLY INCREASING NUMBER OF

6140
04:20:25,165 --> 04:20:30,503
R&Ds WE SEE IN OUR OFFICE.

6141
04:20:30,503 --> 04:20:33,473
SO YOU'LL SEE ORANGE DEPICTING

6142
04:20:33,473 --> 04:20:36,009
EXPANDED ACCESS INDs THAT WE

6143
04:20:36,009 --> 04:20:38,178
WOULD SEE WITHIN THE GIVEN YEARS

6144
04:20:38,178 --> 04:20:42,115
AT THE BOTTOM, RANGES FROM 1963

6145
04:20:42,115 --> 04:20:43,316
TO 2002.

6146
04:20:43,316 --> 04:20:46,085
SO YOU CAN SEE JUST THE SHEER

6147
04:20:46,085 --> 04:20:48,354
AMOUNT OF FILES WE SEE IN OUR

6148
04:20:48,354 --> 04:20:48,688
OFFICE.

6149
04:20:48,688 --> 04:20:51,357
THE BLUE BAR IS REPRESENTATIVE

6150
04:20:51,357 --> 04:20:54,294
OF RESEARCH INDs WE SEE.

6151
04:20:54,294 --> 04:20:55,595
AND WHAT'S INTERESTING IS THAT

6152
04:20:55,595 --> 04:20:59,866
OVER THE RECENT YEARS YOU'LL SEE

6153
04:20:59,866 --> 04:21:01,100
THIS INCREASE IN EXPANDED IND

6154
04:21:01,100 --> 04:21:05,038
REQUEST WE'RE SEEING IN OUR

6155
04:21:05,038 --> 04:21:07,740
OFFICE, EXPANDED MEANS

6156
04:21:07,740 --> 04:21:08,842
COMPASSIONATE USE, ONE-OFF

6157
04:21:08,842 --> 04:21:12,111
RATHER THAN A REAL CLINICAL

6158
04:21:12,111 --> 04:21:15,615
STUDY OR A CONTROLLED CLINICAL

6159
04:21:15,615 --> 04:21:17,283
STUDY.

6160
04:21:17,283 --> 04:21:19,352
THE GROUP IS ALSO SEEN IN

6161
04:21:19,352 --> 04:21:20,220
DIFFERENT TYPES OF MEETINGS AND

6162
04:21:20,220 --> 04:21:23,056
REQUESTS WE RECEIVE IN OUR

6163
04:21:23,056 --> 04:21:24,891
OFFICE, IT'S REALLY DIFFICULT TO

6164
04:21:24,891 --> 04:21:28,061
KEEP UP, BUT THIS IS DEPICTING

6165
04:21:28,061 --> 04:21:34,267
EACH BAR FROM 2010 TO 2022.

6166
04:21:34,267 --> 04:21:38,638
SO, YOU CAN SEE JUST PICTORIALLY

6167
04:21:38,638 --> 04:21:41,241
THE GROWTH OF THIS FIELD THAT

6168
04:21:41,241 --> 04:21:44,344
WE'RE FEELING JUST FROM THE FDA

6169
04:21:44,344 --> 04:21:46,980
LENS.

6170
04:21:46,980 --> 04:21:49,048
ADDED TO THE CHALLENGES OF

6171
04:21:49,048 --> 04:21:52,285
GROWTH IS THE COMPLEXITY OF THE

6172
04:21:52,285 --> 04:21:52,752
FIELD.

6173
04:21:52,752 --> 04:21:55,255
YOU'VE ALL TOUCHED UPON THIS

6174
04:21:55,255 --> 04:21:57,557
TODAY, SOMETHING WE'RE ALL

6175
04:21:57,557 --> 04:21:58,391
GRAPPLING WITH.

6176
04:21:58,391 --> 04:21:59,959
SO, CELL AND GENE THERAPY

6177
04:21:59,959 --> 04:22:02,295
PRODUCTS NOT ONLY ENCOMPASS A

6178
04:22:02,295 --> 04:22:03,696
WIDE VARIETY OF PRODUCTS BUT

6179
04:22:03,696 --> 04:22:06,099
THEY PRESENT COMMON CONCERNS

6180
04:22:06,099 --> 04:22:09,369
WHETHER IT BE AUTOLOGOUS OR

6181
04:22:09,369 --> 04:22:10,536
ALLOGENEIC REGARDING COMPLEXITY

6182
04:22:10,536 --> 04:22:13,406
OF THE PRODUCTS, MECHANISM OF

6183
04:22:13,406 --> 04:22:16,175
ACTION, ALL ASPECTS OF

6184
04:22:16,175 --> 04:22:18,011
MANUFACTURING AND CONTROLS.

6185
04:22:18,011 --> 04:22:18,811
IN ADDITION, THERE'S

6186
04:22:18,811 --> 04:22:19,879
SPECIFICALLY CONCERNS RELATED TO

6187
04:22:19,879 --> 04:22:23,716
THE ORIGIN OF THE MATERIALS WE

6188
04:22:23,716 --> 04:22:26,085
HAVE TO BE MINDFUL OF.

6189
04:22:26,085 --> 04:22:29,956
AND SO THIS IS JUST A COMPLEX

6190
04:22:29,956 --> 04:22:30,523
AMOUNT OF MANUFACTURING

6191
04:22:30,523 --> 04:22:35,862
INFORMATION TO BE ON TOP OF.

6192
04:22:35,862 --> 04:22:38,932
IN ADDITION, THERE'S A

6193
04:22:38,932 --> 04:22:39,565
COMPLEXITY OF PRODUCT

6194
04:22:39,565 --> 04:22:40,366
DEVELOPMENT LIFE CYCLE THAT

6195
04:22:40,366 --> 04:22:44,837
NEEDS TO BE TAKEN INTO ACCOUNT 

6196
04:22:44,837 --> 04:22:49,342
IN THE DEVELOPMENT OF CDCGT,

6197
04:22:49,342 --> 04:22:50,410
DIFFICULT TO COMPLETE, OFTEN

6198
04:22:50,410 --> 04:22:54,681
BLURRED BY A SMALL FEASIBILITY

6199
04:22:54,681 --> 04:23:00,053
PROGRESSING INTO A SMALL PIVOTAL

6200
04:23:00,053 --> 04:23:01,254
CLINICAL STUDY WITH INCOMPLETE

6201
04:23:01,254 --> 04:23:02,722
PRODUCT CHARACTERIZATION

6202
04:23:02,722 --> 04:23:04,991
INFORMATION THAT WE HAVE TO

6203
04:23:04,991 --> 04:23:09,195
DECIPHER.

6204
04:23:09,195 --> 04:23:14,300
AND SO THESE ARE ALL DIFFICULT 

6205
04:23:14,300 --> 04:23:18,604
AREAS THAT MAKE IT HARD TO -- IN

6206
04:23:18,604 --> 04:23:21,107
PROGRESSING THE FIELD, CGT

6207
04:23:21,107 --> 04:23:21,541
PRODUCTS.

6208
04:23:21,541 --> 04:23:24,077
SO THE NEXT FEW SLIDES ALL

6209
04:23:24,077 --> 04:23:26,145
FURTHER BREAK DOWN THINGS INTO

6210
04:23:26,145 --> 04:23:27,814
CHALLENGES THAT WE OBSERVED

6211
04:23:27,814 --> 04:23:30,683
DURING EARLY PHASE AND ALSO IN

6212
04:23:30,683 --> 04:23:33,686
LATE PHASE STUDIES.

6213
04:23:33,686 --> 04:23:35,588
 

6214
04:23:35,588 --> 04:23:37,957
SO, DURING EARLY PHASE THE FOCUS

6215
04:23:37,957 --> 04:23:41,594
IS ON SAFETY.

6216
04:23:41,594 --> 04:23:43,429
SUCH AS DONOR ELIGIBILITY WHICH

6217
04:23:43,429 --> 04:23:46,399
YOU TOUCHED ON, DIFFICULT WITH

6218
04:23:46,399 --> 04:23:50,236
iPSCs AND DONOR THAT'S CHOSEN

6219
04:23:50,236 --> 04:23:51,337
FROM THE BEGINNING, NOT HAVING A

6220
04:23:51,337 --> 04:23:54,707
LOT OF CHOICES BEYOND THE DONOR

6221
04:23:54,707 --> 04:23:56,142
YOU HAVE.

6222
04:23:56,142 --> 04:24:01,381
THERE'S ALSO QUALIFICATION OF

6223
04:24:01,381 --> 04:24:05,318
SAFETY ASSAYS, MICROPLASMA,

6224
04:24:05,318 --> 04:24:06,986
ENDOTOXIN, ALSO REAGENT

6225
04:24:06,986 --> 04:24:08,421
QUALIFYIFICATION THAT'S VERY

6226
04:24:08,421 --> 04:24:09,188
IMPORTANT, FREQUENT OBSERVATION

6227
04:24:09,188 --> 04:24:13,126
FOR HOLD ISSUES THAT WE SEE.

6228
04:24:13,126 --> 04:24:15,361
AND I WAS VERY INTERESTED TO

6229
04:24:15,361 --> 04:24:16,929
HERE THERE ARE A LOT OF, YOU

6230
04:24:16,929 --> 04:24:19,465
KNOW, THAT THERE ARE AWARENESS

6231
04:24:19,465 --> 04:24:21,200
OF DELIVERY SYSTEMS AND THE

6232
04:24:21,200 --> 04:24:24,170
CONCERNS RELATED TO DELIVERY

6233
04:24:24,170 --> 04:24:24,804
SYSTEMS THAT YOU'RE

6234
04:24:24,804 --> 04:24:25,805
CONTEMPLATING BECAUSE THAT'S

6235
04:24:25,805 --> 04:24:30,710
ALSO AN AREA THAT WE FREQUENTLY

6236
04:24:30,710 --> 04:24:33,346
SEE THAT REQUIRES A LOT OF BACK

6237
04:24:33,346 --> 04:24:34,881
AND FORTH TO GET ADDITIONAL

6238
04:24:34,881 --> 04:24:35,748
INFORMATION REGARDING.

6239
04:24:35,748 --> 04:24:37,150
AND I JUST WANT TO MAKE SURE,

6240
04:24:37,150 --> 04:24:40,053
YOU KNOW, HIGHLIGHT THIS IS AN

6241
04:24:40,053 --> 04:24:42,255
ALL-INCLUSIVE LIST, JUST A

6242
04:24:42,255 --> 04:24:43,990
HIGHLIGHT OF THINGS WE'RE

6243
04:24:43,990 --> 04:24:44,357
SEEING.

6244
04:24:44,357 --> 04:24:48,494
SO, JUST TO TOUCH UPON DONOR

6245
04:24:48,494 --> 04:24:49,595
ELIGIBILITY, SO SINCE I'M A

6246
04:24:49,595 --> 04:24:53,833
REGULATOR I'LL THROW OUT

6247
04:24:53,833 --> 04:24:57,870
REGULATION NUMBERS FOR YOU.

6248
04:24:57,870 --> 04:25:00,306
FOR ALLOGENEIC PRODUCTS, NEEDS

6249
04:25:00,306 --> 04:25:02,241
TO MEET DONOR -- NEEDS TO BE

6250
04:25:02,241 --> 04:25:06,946
DETERMINED FOR DONOR TESTING AND

6251
04:25:06,946 --> 04:25:08,281
SCREENING PER 1221 CFR 1271.

6252
04:25:08,281 --> 04:25:09,782
THAT'S A REQUIREMENT THAT WENT

6253
04:25:09,782 --> 04:25:11,217
INTO EFFECT IN 2005.

6254
04:25:11,217 --> 04:25:14,187
SO FOR ANY DONOR MATERIAL THAT

6255
04:25:14,187 --> 04:25:17,690
YOU USE AFTER 2005, THERE IS A

6256
04:25:17,690 --> 04:25:19,459
STRICT REGULATION OF THINGS THAT

6257
04:25:19,459 --> 04:25:21,327
SHOULD BE MET.

6258
04:25:21,327 --> 04:25:23,496
AND THESE ARE FAIRLY WELL LAID

6259
04:25:23,496 --> 04:25:26,599
OUT IN OUR REGULATIONS AND

6260
04:25:26,599 --> 04:25:27,433
VARIOUS GUIDELINES, SOME

6261
04:25:27,433 --> 04:25:29,202
GUIDELINES I'VE PUT ON THE

6262
04:25:29,202 --> 04:25:29,669
SLIDE.

6263
04:25:29,669 --> 04:25:30,503
I APOLOGIZE, BUT THE LINKS, IF

6264
04:25:30,503 --> 04:25:33,606
YOU GET A COPY OF THESE SLIDES,

6265
04:25:33,606 --> 04:25:35,241
THE LINKS AREN'T ACTUALLY --

6266
04:25:35,241 --> 04:25:37,443
THEY ARE NOT CORRECT SO JUST

6267
04:25:37,443 --> 04:25:38,511
GOOGLE THE GUIDANCE NAME AND IT

6268
04:25:38,511 --> 04:25:45,852
WILL GET YOU TO THE RIGHT

6269
04:25:45,852 --> 04:25:48,287
DOCUMENT. 

6270
04:25:48,287 --> 04:25:52,825
THERE ARE TWO COMPONENTS FOR

6271
04:25:52,825 --> 04:25:53,726
DONOR ELIGIBILITY.

6272
04:25:53,726 --> 04:25:54,894
SCREENING AND MEDICAL RECORDS,

6273
04:25:54,894 --> 04:25:56,863
AND THEN THERE'S DONOR TESTING

6274
04:25:56,863 --> 04:25:59,732
ASPECTS FOR THE SPECIMEN THAT'S

6275
04:25:59,732 --> 04:26:00,233
COLLECTED.

6276
04:26:00,233 --> 04:26:01,634
AND OUR REGULATIONS SPELL OUT

6277
04:26:01,634 --> 04:26:03,102
WHAT THE WINDOW OF TIME SHOULD

6278
04:26:03,102 --> 04:26:06,272
BE FOR THE COLLECTION OF THOSE

6279
04:26:06,272 --> 04:26:09,175
SPECIMENS FOR TESTING.

6280
04:26:09,175 --> 04:26:13,279
AND ALSO, THERE ARE SPECIFIC FDA

6281
04:26:13,279 --> 04:26:16,782
LICENSE KITS THAT SHOULD BE USED

6282
04:26:16,782 --> 04:26:18,217
AT CLIA-CERTIFIED LABS.

6283
04:26:18,217 --> 04:26:21,854
SO ALL THESE ASPECTS ARE

6284
04:26:21,854 --> 04:26:24,457
ACTUALLY FAIRLY WELL OUTLINED IN

6285
04:26:24,457 --> 04:26:26,392
OUR -- ON OUR WEBSITES AT FDA.

6286
04:26:26,392 --> 04:26:28,261
THEY MIGHT BE A LITTLE DIFFICULT

6287
04:26:28,261 --> 04:26:29,462
TO FIND, BUT THEY ARE OUT THERE

6288
04:26:29,462 --> 04:26:33,432
AND THEY DO SPELL IT OUT PRETTY

6289
04:26:33,432 --> 04:26:36,903
-- YOU KNOW, PRETTY SPECIFIC IN

6290
04:26:36,903 --> 04:26:38,905
TERMS OF THE NAME OF THE

6291
04:26:38,905 --> 04:26:40,273
COMPANY, THE MODEL, YOU KNOW,

6292
04:26:40,273 --> 04:26:41,941
THE KITS YOU SHOULD BE USING.

6293
04:26:41,941 --> 04:26:43,910
ALL THAT IS SPELLED OUT.

6294
04:26:43,910 --> 04:26:45,811
IT'S JUST A LOT OF INFORMATION

6295
04:26:45,811 --> 04:26:48,981
THAT YOU HAVE TO WADE THROUGH TO

6296
04:26:48,981 --> 04:26:50,583
UNDERSTAND EXACTLY WHAT NEEDS TO

6297
04:26:50,583 --> 04:26:50,983
BE DONE.

6298
04:26:50,983 --> 04:26:54,187
SO A LOT OF TIMES WHERE WE'VE

6299
04:26:54,187 --> 04:26:56,589
RUN INTO ISSUES WHEN THERE ARE

6300
04:26:56,589 --> 04:26:58,124
FOREIGN DONORS BEING USED, AND

6301
04:26:58,124 --> 04:27:01,561
ALSO WHEN THESE DONOR SPECIMENS

6302
04:27:01,561 --> 04:27:04,697
ARE -- DONORS ARE LOCATED IN A

6303
04:27:04,697 --> 04:27:08,267
FOREIGN LOCATION, SO, YOU KNOW,

6304
04:27:08,267 --> 04:27:09,635
ACCESS TO CLIA-CERTIFIED LABS

6305
04:27:09,635 --> 04:27:12,805
ARE MAYBE DIFFICULT TO FIND.

6306
04:27:12,805 --> 04:27:15,174
SO, BUT JUST THINGS TO BE

6307
04:27:15,174 --> 04:27:19,278
MINDFUL OF WHEN YOU ARE USING

6308
04:27:19,278 --> 04:27:20,446
ALLO DONORS.

6309
04:27:20,446 --> 04:27:30,856
ANOTHER AREA, BIG AREA, 

6310
04:27:31,157 --> 04:27:32,091
ESPECIALLY WITH iPSCs,

6311
04:27:32,091 --> 04:27:34,460
REAGENTS, ANOTHER HUGE AREA OF

6312
04:27:34,460 --> 04:27:36,896
COMMUNICATION WE HAVE, RECOMMEND

6313
04:27:36,896 --> 04:27:41,033
SPONSORS USE THE HIGHEST QUALITY

6314
04:27:41,033 --> 04:27:42,568
REAGENT THAT'S AVAILABLE.

6315
04:27:42,568 --> 04:27:43,903
RESEARCH GRADE REAGENTS CAN BE

6316
04:27:43,903 --> 04:27:51,777
USED IF IT IS PROPERLY

6317
04:27:51,777 --> 04:27:56,249
QUALIFIED. 

6318
04:27:56,249 --> 04:27:58,050
ALL HUMAN, ANIMAL REAGENTS THERE

6319
04:27:58,050 --> 04:28:05,258
ARE A MIR KWR5D OF SES.

6320
04:28:05,258 --> 04:28:06,492
 MYRIAD OF CONSIDERATIONS.

6321
04:28:06,492 --> 04:28:09,028
IF THE VENDOR IS MISSING ON

6322
04:28:09,028 --> 04:28:12,765
CERTAIN TEST, EXPECTATION IS THE

6323
04:28:12,765 --> 04:28:16,068
SPONSOR OF THE CGD PRODUCT IS

6324
04:28:16,068 --> 04:28:17,470
ULTIMATELY RESPONSIBLE FOR

6325
04:28:17,470 --> 04:28:21,474
OBTAINING OR CONDUCTING THOSE

6326
04:28:21,474 --> 04:28:22,308
TESTS.

6327
04:28:22,308 --> 04:28:24,277
A LOT OF TIMES A LOT OF VENDORS

6328
04:28:24,277 --> 04:28:26,479
HAVE MASTER FILES WITH FDA FOR

6329
04:28:26,479 --> 04:28:28,114
SPECIFIC REAGENTS, AND WE ASK

6330
04:28:28,114 --> 04:28:30,516
THAT YOU DO USE THOSE RESOURCES

6331
04:28:30,516 --> 04:28:30,950
THAT ARE AVAILABLE.

6332
04:28:30,950 --> 04:28:33,452
AND WOULD YOU HAVE TO OBTAIN

6333
04:28:33,452 --> 04:28:35,755
THAT FROM YOUR VENDOR FOR A

6334
04:28:35,755 --> 04:28:37,189
LETTER OF AUTHORIZATION TO

6335
04:28:37,189 --> 04:28:38,391
CROSS-REFERENCE, SO THAT YOU

6336
04:28:38,391 --> 04:28:42,662
WOULDN'T HAVE TO PROVIDE THE

6337
04:28:42,662 --> 04:28:45,498
SPECIFIC INFORMATION.

6338
04:28:45,498 --> 04:28:47,633
THIS HAS BEEN TOUCHED UPON BY

6339
04:28:47,633 --> 04:28:53,939
ALMOST EVERYONE, AND IN A LOT OF

6340
04:28:53,939 --> 04:28:54,440
THE QUESTION-AND-ANSWER

6341
04:28:54,440 --> 04:28:57,643
DISCUSSIONS TODAY.

6342
04:28:57,643 --> 04:28:58,678
YOU KNOW, CAN'T STRESS ENOUGH

6343
04:28:58,678 --> 04:29:02,248
THAT YOU HAVE TO UNDERSTAND THE

6344
04:29:02,248 --> 04:29:02,715
PRODUCT.

6345
04:29:02,715 --> 04:29:05,618
EXPLORING PRODUCT ATRY BEAUTS

6346
04:29:05,618 --> 04:29:08,054
EARLY IN DEVELOPMENT WILL

6347
04:29:08,054 --> 04:29:18,597
IDENTIFY YOUR IFY YOUR CRITICAL

6348
04:29:20,633 --> 04:29:21,367
QUALITY ATTRIBUTES.

6349
04:29:21,367 --> 04:29:25,037
THIS WOULD HELP GETTING YOUR

6350
04:29:25,037 --> 04:29:26,739
PRODUCT THROUGH.

6351
04:29:26,739 --> 04:29:28,240
EXPLORING MULTIPLE PRODUCT ATRY

6352
04:29:28,240 --> 04:29:30,409
DUTIES DURING EARLY PRODUCT

6353
04:29:30,409 --> 04:29:30,943
DEVELOPMENT IS PARAMOUNT.

6354
04:29:30,943 --> 04:29:33,512
IF YOU NARROW DOWN THE CRITICAL

6355
04:29:33,512 --> 04:29:36,882
AT TRIBRUTES THAT MEANINGFULLY

6356
04:29:36,882 --> 04:29:38,751
DEFINE YOUR PRODUCT, SPONSORS

6357
04:29:38,751 --> 04:29:40,586
MAY FIND THAT SOME ASSAYS ARE

6358
04:29:40,586 --> 04:29:43,556
DIFFICULT TO VALIDATE AS WELL.

6359
04:29:43,556 --> 04:29:49,028
IT'S ALWAYS HELPFUL TO HAVE

6360
04:29:49,028 --> 04:29:49,795
CHOICES AND ALTERNATIVE

6361
04:29:49,795 --> 04:29:54,500
ATTRIBUTES AND METHODS YOU MIGHT

6362
04:29:54,500 --> 04:29:55,034
RELY ON.

6363
04:29:55,034 --> 04:29:57,269
ALSO CQAs HELP IN

6364
04:29:57,269 --> 04:29:58,571
DEMONSTRATING PRODUCT

6365
04:29:58,571 --> 04:30:01,807
COMPARABILITY WHICH I'LL GO OVER

6366
04:30:01,807 --> 04:30:12,318
REGARDING ESPECIALLY LLY WITH

6367
04:30:14,487 --> 04:30:15,488
LATE PHASE STUDIES, ALREADY

6368
04:30:15,488 --> 04:30:16,956
CHANGES FOLKS WILL ENCOUNTER AS

6369
04:30:16,956 --> 04:30:19,191
DEVELOPMENT PROGRESSES.

6370
04:30:19,191 --> 04:30:20,726
IN ADDITION TO THE CQAs

6371
04:30:20,726 --> 04:30:22,862
THERE'S A LOT OF SPECIFIC CASES

6372
04:30:22,862 --> 04:30:25,798
WHICH SOME CQAs COULD BE PART

6373
04:30:25,798 --> 04:30:30,136
OF YOUR LOT RELEASE SPECS.

6374
04:30:30,136 --> 04:30:31,737
THESE ARE IMPORTANT BECAUSE, YOU

6375
04:30:31,737 --> 04:30:33,906
KNOW, DURING EARLY PHASE

6376
04:30:33,906 --> 04:30:35,441
SPONSORS SHOULD EXPLORE AS MUCH

6377
04:30:35,441 --> 04:30:38,511
AS YOU CAN TO DETERMINE WHAT

6378
04:30:38,511 --> 04:30:41,380
ATTRIBUTES TO INCLUDE IN LOT

6379
04:30:41,380 --> 04:30:43,115
RELEASE SPECS, AND YOU WANT TO

6380
04:30:43,115 --> 04:30:45,317
SET THE CORRECT RELEASE CRITERIA

6381
04:30:45,317 --> 04:30:47,620
FOR SPECS AND, YOU KNOW, WHAT'S

6382
04:30:47,620 --> 04:30:52,291
CORRECT IS REALLY YOUR

6383
04:30:52,291 --> 04:30:54,460
MANUFACTURE EXPERIENCE, WHAT

6384
04:30:54,460 --> 04:30:55,060
MAKES SENSE, JUSTIFICATION,

6385
04:30:55,060 --> 04:30:56,061
JUSTIFICATION, JUSTIFICATION

6386
04:30:56,061 --> 04:30:58,230
WITH US.

6387
04:30:58,230 --> 04:31:03,135
SO SOME -- THESE ARE SOME COMMON

6388
04:31:03,135 --> 04:31:11,143
ISSUES THAT WE FIND WITH LOT 

6389
04:31:11,143 --> 04:31:12,478
RELEASE CRITERIA AND

6390
04:31:12,478 --> 04:31:13,446
SPECIFICATIONS, WE JUST NEED A

6391
04:31:13,446 --> 04:31:14,613
LOT OF JUSTIFICATION, WHATEVER

6392
04:31:14,613 --> 04:31:15,514
YOU HAVE.

6393
04:31:15,514 --> 04:31:17,917
IT NEEDS TO MAKE SENSE,

6394
04:31:17,917 --> 04:31:19,685
SCIENTIFIC SENSE, AND HOW YOU'RE

6395
04:31:19,685 --> 04:31:20,519
SETTING UP.

6396
04:31:20,519 --> 04:31:27,460
DO YOU HAVE DATA TO SUPPORT YOUR

6397
04:31:27,460 --> 04:31:27,993
CRITERIA?

6398
04:31:27,993 --> 04:31:29,962
SO, LASTLY, ON THIS EARLY PHASE

6399
04:31:29,962 --> 04:31:32,598
PART, I WANT TO TALK ABOUT

6400
04:31:32,598 --> 04:31:35,201
ANOTHER COMMON COMMUNICATION

6401
04:31:35,201 --> 04:31:38,003
THAT I MENTIONED, WHICH IS HOW

6402
04:31:38,003 --> 04:31:40,139
IS THE PRODUCT BEING

6403
04:31:40,139 --> 04:31:41,140
ADMINISTERED.

6404
04:31:41,140 --> 04:31:43,576
EVEN FOR SIMPLE ADMINISTRATIONS

6405
04:31:43,576 --> 04:31:47,680
FOR INTRADERMAL INJECTION OR

6406
04:31:47,680 --> 04:31:49,682
EVEN IV INFUSIONS WE LIKE TO SEE

6407
04:31:49,682 --> 04:31:50,983
INFORMATION ON SYRINGE AND

6408
04:31:50,983 --> 04:31:52,751
NEEDLE GAUGE FOR EXAMPLE FOR

6409
04:31:52,751 --> 04:31:54,286
SOMETHING SIMPLE LIKE THAT.

6410
04:31:54,286 --> 04:31:56,555
IT'S REALLY TO UNDERSTAND THE

6411
04:31:56,555 --> 04:31:59,625
WORST CASE CONDITIONS THAT CELLS

6412
04:31:59,625 --> 04:32:01,494
WILL UNDERGO, AND DETERMINE THE

6413
04:32:01,494 --> 04:32:03,262
COMPATIBILITY OF THE CELL

6414
04:32:03,262 --> 04:32:04,663
PRODUCT WITH THE DELIVERY

6415
04:32:04,663 --> 04:32:07,399
SYSTEM.

6416
04:32:07,399 --> 04:32:12,004
FOR THINGS LIKE DELIVERY BY

6417
04:32:12,004 --> 04:32:13,305
CATHETERS, ARE SPONSORS USING

6418
04:32:13,305 --> 04:32:16,075
FDA CLEARED OR APPROVED DEVICES

6419
04:32:16,075 --> 04:32:19,111
INTENDED FOR DELIVERY OF A DRUG,

6420
04:32:19,111 --> 04:32:20,646
YOU KNOW, BECAUSE SOMETIMES THEY

6421
04:32:20,646 --> 04:32:24,049
ARE JUST -- THEY ARE NOT

6422
04:32:24,049 --> 04:32:27,553
INTENDED TO DELIVER DRUGS

6423
04:32:27,553 --> 04:32:30,723
THROUGH, IF SHEATHS ARE

6424
04:32:30,723 --> 04:32:32,892
INTRODUCERS AND YOU'RE PUTTING A

6425
04:32:32,892 --> 04:32:34,593
DRUG INTO THE LUMEN WASN'T

6426
04:32:34,593 --> 04:32:39,598
INTENDED OR CLEARED OR APPROVED

6427
04:32:39,598 --> 04:32:43,435
FOR THAT USE.

6428
04:32:43,435 --> 04:32:44,637
ARE THERE CUMULATIVE ENDOTOXIN

6429
04:32:44,637 --> 04:32:45,971
CONCERNS THAT WE NEED TO BE

6430
04:32:45,971 --> 04:32:48,574
CONCERNED ABOUT?

6431
04:32:48,574 --> 04:32:50,342
FOR INSTANCE, ANYTHING THAT'S

6432
04:32:50,342 --> 04:32:51,610
GOING INTO THE INTRAOCULAR

6433
04:32:51,610 --> 04:32:56,549
SPACE, THERE IS A LOWER

6434
04:32:56,549 --> 04:32:59,618
ENDOTOXIN LIMIT BECAUSE OF TOXIC

6435
04:32:59,618 --> 04:33:03,188
INTERSEGMENT SYNDROME, SO ARE

6436
04:33:03,188 --> 04:33:06,859
THOSE THINGS BEING CONSIDERED. 

6437
04:33:06,859 --> 04:33:08,928
IN GENERAL, KNOW THE FDA REGULAR

6438
04:33:08,928 --> 04:33:12,531
THAT LOWER STATUS AND DELIVERY

6439
04:33:12,531 --> 04:33:15,467
SYSTEM AND PERFORM COMPATIBILITY

6440
04:33:15,467 --> 04:33:16,569
TESTING, WHICH MEANS PASSING THE

6441
04:33:16,569 --> 04:33:20,506
PRODUCT THROUGH THE DELIVERY 

6442
04:33:20,506 --> 04:33:22,041
DEVICES AND SEEING THE PRE AND

6443
04:33:22,041 --> 04:33:22,675
POST PRODUCT AND MAKING SURE

6444
04:33:22,675 --> 04:33:25,978
THAT IT IS THE SAME AS WHAT YOU

6445
04:33:25,978 --> 04:33:29,415
PUT IN ONE END AND THAT YOU KNOW

6446
04:33:29,415 --> 04:33:32,451
HOW MUCH YOU'RE DELIVERING.

6447
04:33:32,451 --> 04:33:36,155
SO I'M GOING TO MAKE THIS VERY

6448
04:33:36,155 --> 04:33:41,760
QUICK BECAUSE I'M OUT OF TIME. 

6449
04:33:41,760 --> 04:33:43,295
BUT REGARDING LATE PHASE, YOU

6450
04:33:43,295 --> 04:33:46,365
WENT OVER A LOT OF THIS SO I

6451
04:33:46,365 --> 04:33:50,402
THINK WHAT I'LL HIGHLIGHT IS

6452
04:33:50,402 --> 04:33:52,037
THAT BEFORE ENTERING YOUR PHASE

6453
04:33:52,037 --> 04:33:54,106
3 STUDIES OR CLINICAL STUDIES AS

6454
04:33:54,106 --> 04:33:58,877
INTENDED TO SUPPORT YOUR PRIMARY

6455
04:33:58,877 --> 04:34:03,549
EFFICACY FOR -- IN SUPPORT OF

6456
04:34:03,549 --> 04:34:04,950
BLA HAVE YOUR POTENCY ASSAY IN

6457
04:34:04,950 --> 04:34:06,151
PLACE BEFORE STARTING THAT

6458
04:34:06,151 --> 04:34:06,485
STUDY.

6459
04:34:06,485 --> 04:34:08,220
WHEN I SAY PLEASE HAVE YOUR

6460
04:34:08,220 --> 04:34:11,223
POTENCY ASSAY IN PLACE, IT MEANS

6461
04:34:11,223 --> 04:34:14,159
HAVING A QUALIFIED ASSAY IN

6462
04:34:14,159 --> 04:34:14,727
PLACE.

6463
04:34:14,727 --> 04:34:19,832
VALIDATION CAN OCCUR AT BLA, IN

6464
04:34:19,832 --> 04:34:21,033
YOUR BLA SITUATION.

6465
04:34:21,033 --> 04:34:22,568
AND I WON'T GO OVER THE

6466
04:34:22,568 --> 04:34:23,669
REGULATORY DEFINITION BECAUSE

6467
04:34:23,669 --> 04:34:28,707
YOU CAN LOOK UP THE REGULATORY

6468
04:34:28,707 --> 04:34:29,108
DEFINITION.

6469
04:34:29,108 --> 04:34:31,677
AND THE IMPORTANCE OF POTENCY

6470
04:34:31,677 --> 04:34:33,812
ASSAY ATTRIBUTE, I THINK WE'RE

6471
04:34:33,812 --> 04:34:35,748
ALL CLEAR ON THIS SO I'LL ALSO

6472
04:34:35,748 --> 04:34:38,450
GO OVER QUICKLY OVER THIS.

6473
04:34:38,450 --> 04:34:41,987
BUT HAVING A QUANTITATIVE 

6474
04:34:41,987 --> 04:34:44,056
POTENCY ASSAY THAT ACTUALLY MAY

6475
04:34:44,056 --> 04:34:46,358
HAVE TIES TO CLINICAL EVIDENCE

6476
04:34:46,358 --> 04:34:51,263
OR MECHANISM OF ACTION IS VERY

6477
04:34:51,263 --> 04:34:55,334
HELPFUL FOR SUPPORT OF YOUR

6478
04:34:55,334 --> 04:34:57,569
PRODUCT DEVELOPMENT.

6479
04:34:57,569 --> 04:34:58,704
SO LET'S GO THROUGH

6480
04:34:58,704 --> 04:35:01,006
MANUFACTURING CHANGES, LIKE I

6481
04:35:01,006 --> 04:35:02,875
SAID, ARE INEVITABLE, AND THIS

6482
04:35:02,875 --> 04:35:07,346
IS WHERE  POTENCY ASSAY WILL BE

6483
04:35:07,346 --> 04:35:14,353
HELP FOLLOW DO A PROPER

6484
04:35:14,353 --> 04:35:15,320
COMPARABILITY ANALYSIS.

6485
04:35:15,320 --> 04:35:16,088
COMPARABILITY STUDIES WILL BE

6486
04:35:16,088 --> 04:35:17,756
DEPENDENT ON HOW MUCH CHANGE

6487
04:35:17,756 --> 04:35:21,393
YOU'RE MAKING, WHAT PHASE OF

6488
04:35:21,393 --> 04:35:22,761
YOUR CLINICAL STUDY YOU'RE IN. 

6489
04:35:22,761 --> 04:35:27,599
OBVIOUSLY THE LATER THE PHASE, 

6490
04:35:27,599 --> 04:35:29,168
THE MORE COMPARABILITY STUDIES

6491
04:35:29,168 --> 04:35:34,606
OR DATA WOULD BE NEEDED TO

6492
04:35:34,606 --> 04:35:34,973
DEMONSTRATE.

6493
04:35:34,973 --> 04:35:40,546
BUT I'M GOING TO GO THROUGH

6494
04:35:40,546 --> 04:35:44,817
JUST -- THESE ARE LIMITATIONS ON

6495
04:35:44,817 --> 04:35:46,885
ESTABLISHING COMPARABILITY AND

6496
04:35:46,885 --> 04:35:51,156
THE CHALLENGES THAT WE ENCOUNTER

6497
04:35:51,156 --> 04:35:51,690
TYPICALLY.

6498
04:35:51,690 --> 04:35:54,359
BUT ONE OF THE THINGS ALSO TO BE

6499
04:35:54,359 --> 04:35:57,196
MINDFUL IS THAT IF AT ALL

6500
04:35:57,196 --> 04:36:00,666
POSSIBLE TO USE YOUR COMMERCIAL

6501
04:36:00,666 --> 04:36:01,667
MANUFACTURING PROCESS VERSION

6502
04:36:01,667 --> 04:36:04,603
AND ALSO YOUR INTENDED

6503
04:36:04,603 --> 04:36:06,038
COMMERCIAL MANUFACTURING

6504
04:36:06,038 --> 04:36:08,574
FACILITY, IN YOUR PHASE 3, YOUR

6505
04:36:08,574 --> 04:36:10,442
PIVOTAL STUDY IN SUPPORT OF BLA

6506
04:36:10,442 --> 04:36:12,845
WE SEE A LOT OF HICCUP ON THAT

6507
04:36:12,845 --> 04:36:17,216
WHEN FOLKS ARE COMING IN EVEN AT

6508
04:36:17,216 --> 04:36:18,984
THE STAGE WITH COMMERCIAL

6509
04:36:18,984 --> 04:36:20,619
MANUFACTURING FACILITY.

6510
04:36:20,619 --> 04:36:24,356
AND JUST ONE MORE SLIDE HERE, I

6511
04:36:24,356 --> 04:36:30,229
WANT TO HIGHLIGHT HERE REALLY TO

6512
04:36:30,229 --> 04:36:31,897
KEEP CMC DEVELOPMENT IN LINE

6513
04:36:31,897 --> 04:36:34,066
WITH CLINICAL DEVELOPMENT.

6514
04:36:34,066 --> 04:36:35,534
WE TYPICALLY SEE WHERE CLINICAL

6515
04:36:35,534 --> 04:36:37,770
DEVELOPMENT, WE HAVE CLINICAL

6516
04:36:37,770 --> 04:36:39,738
DATA AND THE DEVELOPMENT JUST

6517
04:36:39,738 --> 04:36:42,174
PUSHES FORWARD WHERE A CMC IS

6518
04:36:42,174 --> 04:36:46,645
STILL STUCK IN A VERY SMALL

6519
04:36:46,645 --> 04:36:47,946
FACILITY OR NON-SCALEUP OSH --

6520
04:36:47,946 --> 04:36:50,783
AND IT'S NOT JUST -- IT'S NOT IN

6521
04:36:50,783 --> 04:36:52,217
ALIGNMENT WITH WHERE THE

6522
04:36:52,217 --> 04:36:55,387
CLINICAL STAGE OF THE

6523
04:36:55,387 --> 04:36:56,655
DEVELOPMENT MAY BE.

6524
04:36:56,655 --> 04:36:57,890
SO, THAT'S ALL I HAVE BECAUSE MY

6525
04:36:57,890 --> 04:36:59,424
NEXT SLIDE IS A SUMMARY SLIDE

6526
04:36:59,424 --> 04:37:01,693
BUT I DO HAVE MY CONTACT

6527
04:37:01,693 --> 04:37:03,362
INFORMATION AT THE END OF THE

6528
04:37:03,362 --> 04:37:05,998
SLIDE DECK THAT EVERYONE IS

6529
04:37:05,998 --> 04:37:07,232
PROBABLY AWARE OF FROM PREVIOUS

6530
04:37:07,232 --> 04:37:08,100
FDA TALKS.

6531
04:37:08,100 --> 04:37:08,700
SO THAT'S IT.

6532
04:37:08,700 --> 04:37:11,370
THANK YOU.

6533
04:37:11,370 --> 04:37:17,509
 

6534
04:37:17,509 --> 04:37:21,113
 

6535
04:37:21,113 --> 04:37:22,648
>> THANK YOU.

6536
04:37:22,648 --> 04:37:24,983
AT THIS POINT WE'RE SHIFTING

6537
04:37:24,983 --> 04:37:28,320
GEARS FROM THINKING BIG IN TERMS

6538
04:37:28,320 --> 04:37:30,856
OF HOW NIH INSTITUTES AND

6539
04:37:30,856 --> 04:37:32,624
CENTERS AND FDA AND NIST CAN

6540
04:37:32,624 --> 04:37:34,726
WORK TOGETHER THINKING ABOUT

6541
04:37:34,726 --> 04:37:44,036
WHAT WE MIGHT DO IN THE

6542
04:37:44,036 --> 04:37:46,839
CELL-BASED THERAPIES CONSORTIUM.

6543
04:37:46,839 --> 04:37:50,342
TO LEAD US UP, THE BESPOKE GENE

6544
04:37:50,342 --> 04:37:52,878
THERAPY CONSORTIUM, THE MODEL

6545
04:37:52,878 --> 04:37:56,048
FOR THE CELL-BASED THERAPIES

6546
04:37:56,048 --> 04:37:56,782
CONSORTIUM.

6547
04:37:56,782 --> 04:37:58,150
I'VE HAD THE LUXURY OF WORKING

6548
04:37:58,150 --> 04:38:02,721
WITH COURTNEY ON A NUMBER OF

6549
04:38:02,721 --> 04:38:05,257
PROJECTS, SHE'S BEEN MADE THEM

6550
04:38:05,257 --> 04:38:05,490
HAPPEN.

6551
04:38:05,490 --> 04:38:11,930
SO IT'S AWFUL GREAT TO HAVE YOU

6552
04:38:11,930 --> 04:38:13,232
WITH US.

6553
04:38:13,232 --> 04:38:14,800
>> THANKS, BOB.

6554
04:38:14,800 --> 04:38:20,272
THANKS, EVERYONE, FOR THE

6555
04:38:20,272 --> 04:38:21,073
OPPORTUNITY TODAY.

6556
04:38:21,073 --> 04:38:22,507
ALL RIGHT.

6557
04:38:22,507 --> 04:38:29,014
AS BOB SAID, I'M COURTNEY

6558
04:38:29,014 --> 04:38:29,581
SILVERTHORN, FOUNDATION FOR

6559
04:38:29,581 --> 04:38:32,317
NATIONAL INSTITUTES OF HEALTH.

6560
04:38:32,317 --> 04:38:34,653
5 01 C3 NON-PROFIT MANDATED BY

6561
04:38:34,653 --> 04:38:36,088
CONGRESS IN THE 1990s TO

6562
04:38:36,088 --> 04:38:38,423
SUPPORT THE MISSION OF THE NIH,

6563
04:38:38,423 --> 04:38:44,663
WE DO THAT IN DIFFERENT WAYS BUT

6564
04:38:44,663 --> 04:38:47,733
ONE OF THE MOST IMPORTANT WAYS

6565
04:38:47,733 --> 04:38:49,701
WE'RE RESPONSIBLE FOR DESIGN,

6566
04:38:49,701 --> 04:38:51,336
FUNDRAISING, EXECUTION OF VERY

6567
04:38:51,336 --> 04:38:54,306
LARGE AND COMPLEX PUBLIC/PRIVATE

6568
04:38:54,306 --> 04:38:54,640
PARTNERSHIPS.

6569
04:38:54,640 --> 04:38:58,577
I ALSO SERVE AS DIRECTOR OF

6570
04:38:58,577 --> 04:39:07,986
THE -- WHICH WAY DO I POINT?

6571
04:39:07,986 --> 04:39:09,621
THERE WE GO.

6572
04:39:09,621 --> 04:39:10,389
EXPLORING MEDICINES PARTNERSHIP

6573
04:39:10,389 --> 04:39:13,358
PROGRAM, THIS IS A SET OF

6574
04:39:13,358 --> 04:39:14,493
PUBLIC/PRIVATE PARTNERSHIPS THAT

6575
04:39:14,493 --> 04:39:16,962
DATE BACK TO BEGINNING IN 2014,

6576
04:39:16,962 --> 04:39:19,731
THAT WERE DESIGNED TO ALIGN THE

6577
04:39:19,731 --> 04:39:23,869
RESOURCES OF THE NIH AND

6578
04:39:23,869 --> 04:39:25,404
RESOURCES OF THE PRIVATE SECTOR

6579
04:39:25,404 --> 04:39:27,039
TO SOLVE CHALLENGES IN FIELDS

6580
04:39:27,039 --> 04:39:28,373
THAT NEITHER THE GOVERNMENT OR

6581
04:39:28,373 --> 04:39:31,076
PRIVATE SECTOR COULD SOLVE ON

6582
04:39:31,076 --> 04:39:32,177
THEIR OWN.

6583
04:39:32,177 --> 04:39:36,315
SINCE 2014, WE HAVE HAD TEN

6584
04:39:36,315 --> 04:39:37,215
PROJECTS, REPRESENTING OVER $830

6585
04:39:37,215 --> 04:39:38,317
MILLION OF INVESTMENT BETWEEN

6586
04:39:38,317 --> 04:39:40,185
THE NIH AND PRIVATE SECTOR,

6587
04:39:40,185 --> 04:39:42,888
WE'RE ABOUT TO CELEBRATE OUR

6588
04:39:42,888 --> 04:39:43,855
10th ANNIVERSARY IN FEBRUARY

6589
04:39:43,855 --> 04:39:45,223
OF NEXT YEAR.

6590
04:39:45,223 --> 04:39:47,726
YOU SEE ACROSS THE BOTTOM LINE

6591
04:39:47,726 --> 04:39:50,996
THE LARGE NUMBERS OF FOR-PROFIT

6592
04:39:50,996 --> 04:39:51,663
ORGANIZATIONS, NON-PROFIT

6593
04:39:51,663 --> 04:39:56,568
ORGANIZATIONS, NIH INSTITUTES 

6594
04:39:56,568 --> 04:39:57,803
AND CENTERS THAT PARTICIPATE IN

6595
04:39:57,803 --> 04:39:58,437
THESE PROJECTS, THAT SPEAKS TO

6596
04:39:58,437 --> 04:39:59,671
THE VALUE OF THE PUBLIC/PRIVATE

6597
04:39:59,671 --> 04:40:01,940
PARTNERSHIP ITSELF BUT ALSO THE

6598
04:40:01,940 --> 04:40:02,941
FOCUS ON PRE-COMPETITIVE

6599
04:40:02,941 --> 04:40:04,242
ADVANCEMENT SO WE CAN BRING

6600
04:40:04,242 --> 04:40:05,344
TOGETHER ORGANIZATIONS THAT

6601
04:40:05,344 --> 04:40:06,678
MIGHT BE COMPETITORS IN THE

6602
04:40:06,678 --> 04:40:09,047
MARKET BUT CAN COME TOGETHER IN

6603
04:40:09,047 --> 04:40:11,249
A NEUTRAL CONVENING AND SHOW

6604
04:40:11,249 --> 04:40:14,186
THEIR EXPERTISE AND GUIDE THE

6605
04:40:14,186 --> 04:40:16,288
PROJECT TO THINGS THAT BENEFIT

6606
04:40:16,288 --> 04:40:20,759
NOT JUST  PARTNERS AND BROADER

6607
04:40:20,759 --> 04:40:21,193
FIELD.

6608
04:40:21,193 --> 04:40:22,561
THIS GIVES A SENSE OF PROJECTS

6609
04:40:22,561 --> 04:40:31,737
IN THE AMP PROGRAM TO DATE.

6610
04:40:31,737 --> 04:40:34,673
WE HAVE A NUMBER OF BCT PARTNERS

6611
04:40:34,673 --> 04:40:36,675
PARTICIPATING IN THIS WORKSHOP.

6612
04:40:36,675 --> 04:40:47,152
I WANT TO  YOU TO KNOW  THE

6613
04:40:54,726 --> 04:41:01,433
BGCT, IT'S DISEAS AGNOSTIC,

6614
04:41:01,433 --> 04:41:03,135
VEALING AAV GENE THERAPIES FOR

6615
04:41:03,135 --> 04:41:04,269
RARE DISEASES PARTICULARLY

6616
04:41:04,269 --> 04:41:05,337
FOCUSED ON MANUFACTURING AND

6617
04:41:05,337 --> 04:41:08,206
CLINICAL WORK INTO AN IND IN THE

6618
04:41:08,206 --> 04:41:09,207
FIRST-IN-HUMAN CLINICAL TRIAL.

6619
04:41:09,207 --> 04:41:12,444
JUST LAST MONTH WE HAD TWO NEW

6620
04:41:12,444 --> 04:41:13,045
NEUROSCIENCE PROJECTS APPROVED

6621
04:41:13,045 --> 04:41:14,646
IN PARKINSON'S DISEASE AND

6622
04:41:14,646 --> 04:41:16,081
RELATED DISORDERS, OUR SECOND

6623
04:41:16,081 --> 04:41:18,016
PHASE OF AMP PD PROJECT AND NEW

6624
04:41:18,016 --> 04:41:19,551
PROJECT IN ALS, YOU CAN SEE AT

6625
04:41:19,551 --> 04:41:22,054
THE BOTTOM WE HAVE SEVERAL OTHER

6626
04:41:22,054 --> 04:41:24,156
PROJECTS IN DEVELOPMENT AS WELL,

6627
04:41:24,156 --> 04:41:27,359
AN EFFORT TO ALIGN DATA ACROSS

6628
04:41:27,359 --> 04:41:28,727
MULTIPLE AMP PROJECTS TO LOOK

6629
04:41:28,727 --> 04:41:29,628
FOR COMMON PATHWAYS OF

6630
04:41:29,628 --> 04:41:31,663
INFLAMMATION AND THEN THE

6631
04:41:31,663 --> 04:41:33,031
CELL-BASED THERAPY CONSORTIUM

6632
04:41:33,031 --> 04:41:36,635
WHICH IS BEING BUILT SOMEWHAT

6633
04:41:36,635 --> 04:41:41,673
OFF THE BGTC MODEL.

6634
04:41:41,673 --> 04:41:44,276
THE CORE PRINCIPLES, SHARED

6635
04:41:44,276 --> 04:41:48,780
GOVERNANCE OF FUNDING BETWEEN 

6636
04:41:48,780 --> 04:41:50,916
NIH AND PRIVATE SECTOR, MOST OF

6637
04:41:50,916 --> 04:41:53,385
THE AMPs HAVE PUBLIC-FACING

6638
04:41:53,385 --> 04:41:55,720
PORTALS OR OTHER WAYS OF

6639
04:41:55,720 --> 04:41:56,888
DISSEMINATING INFORMATION.

6640
04:41:56,888 --> 04:41:59,257
AND AGAIN KEEPING WITH THAT

6641
04:41:59,257 --> 04:42:02,461
PRE-COMPETITIVE ASPECT THAT WE

6642
04:42:02,461 --> 04:42:09,734
DON'T ALLOW PREEMPTIVE PATENTING

6643
04:42:09,734 --> 04:42:10,769
SO IT'S ACCESSIBLE TO THE

6644
04:42:10,769 --> 04:42:12,904
BROADER COMMUNITY AS POSSIBLE.

6645
04:42:12,904 --> 04:42:14,706
THIS OUTLINES A LOT OF WHAT

6646
04:42:14,706 --> 04:42:18,877
WE'VE BEEN  HEARING ABOUT,

6647
04:42:18,877 --> 04:42:26,518
CHALLENGES AND SOLUTIONS IN CELL

6648
04:42:26,518 --> 04:42:27,219
THERAPY PRODUCTION SOURCES,

6649
04:42:27,219 --> 04:42:34,526
CONSIDERINGS ABOUT THE CELL

6650
04:42:34,526 --> 04:42:35,827
SOURCE, MODIFICATIONS, TESTING,

6651
04:42:35,827 --> 04:42:38,363
RELATED ACCEPTANCE CRITERIA, THE

6652
04:42:38,363 --> 04:42:39,164
DISTRIBUTION DELIVERRIVE

6653
04:42:39,164 --> 04:42:40,532
CELL-BASED THERAPIES AND

6654
04:42:40,532 --> 04:42:41,833
CLINICAL APPLICATION, THINGS

6655
04:42:41,833 --> 04:42:44,369
CONSIDERED AS WE'RE BUILDING OUT

6656
04:42:44,369 --> 04:42:45,904
THIS PARTICULAR SOLUTION.

6657
04:42:45,904 --> 04:42:47,305
AND WE'RE ESPECIALLY FOCUSED ON,

6658
04:42:47,305 --> 04:42:49,808
AGAIN, BECAUSE WE'RE LOOKING FOR

6659
04:42:49,808 --> 04:42:51,376
THE OVERLAP BETWEEN THE INTEREST

6660
04:42:51,376 --> 04:42:53,879
OF NIH AND INTEREST OF THE

6661
04:42:53,879 --> 04:42:56,047
PRIVATE SECTOR, SO VERY

6662
04:42:56,047 --> 04:42:58,583
ENCOURAGED TO HEAR ABOUT

6663
04:42:58,583 --> 04:42:59,484
MANUFACTURING AND PROCESSES,

6664
04:42:59,484 --> 04:43:00,785
THINGS THAT WE'LL PROBABLY BE

6665
04:43:00,785 --> 04:43:03,288
THINKING ABOUT AS WE BUILD OUT

6666
04:43:03,288 --> 04:43:09,327
THIS CONSORTIUM, POTENTIALLY 

6667
04:43:09,327 --> 04:43:10,495
LOOKING AT PROCESS DEVELOPMENTS

6668
04:43:10,495 --> 04:43:13,899
FOR MANUFACTURING AND HOW THEY

6669
04:43:13,899 --> 04:43:22,807
SCALE, DETERMINING ALLOGENEIC

6670
04:43:22,807 --> 04:43:25,477
VERSUS AUTOLOGOUS AND TOLERANCE,

6671
04:43:25,477 --> 04:43:27,212
HEARING ABOUT BIOEQUIVALENCE

6672
04:43:27,212 --> 04:43:29,281
BETWEEN DIFFERENT TIMES OF

6673
04:43:29,281 --> 04:43:30,081
CELLULAR-BASED THERAPIES,

6674
04:43:30,081 --> 04:43:31,149
REGULATORY RISK IS A

6675
04:43:31,149 --> 04:43:33,218
CONSIDERATION AND WHEN WE'RE IN

6676
04:43:33,218 --> 04:43:34,319
DISEASE AGNOSTIC STATES THERE'S

6677
04:43:34,319 --> 04:43:36,288
A BROAD RANGE OF RISK

6678
04:43:36,288 --> 04:43:39,891
ASSESSMENTS DEPENDING ON THE 

6679
04:43:39,891 --> 04:43:41,626
SPECIFIC DISEASE OR DISORDER.

6680
04:43:41,626 --> 04:43:43,328
TISSUE INCORPORATION OF

6681
04:43:43,328 --> 04:43:44,062
MANUFACTURING PRODUCTS AND

6682
04:43:44,062 --> 04:43:45,463
CLINICAL TRIAL DESIGN AND

6683
04:43:45,463 --> 04:43:47,966
INFORMED CONSENT FOR LIVING

6684
04:43:47,966 --> 04:43:48,867
THERAPIES.

6685
04:43:48,867 --> 04:43:52,671
SO A PRETTY LENGTHY LIST, THINGS

6686
04:43:52,671 --> 04:43:55,106
WE'RE EXCITED TO THINK ABOUT

6687
04:43:55,106 --> 04:43:55,373
TACKLING.

6688
04:43:55,373 --> 04:43:57,175
WE'RE NOT GOING ABOUT THIS IN A

6689
04:43:57,175 --> 04:43:57,409
VACUUM.

6690
04:43:57,409 --> 04:44:03,315
WE'VE HEARD ABOUT PRIOR WORK IN

6691
04:44:03,315 --> 04:44:04,416
THE CELL-BASED THERAPY SPACE,

6692
04:44:04,416 --> 04:44:09,120
LOOKING TO WORK ALREADY DONE.

6693
04:44:09,120 --> 04:44:10,622
GAO REPORTS AND FDA CONSENSUS

6694
04:44:10,622 --> 04:44:15,627
STANDARDS, PRIOR NIH EFFORTS IN

6695
04:44:15,627 --> 04:44:17,529
THE RMIP IMPACT PROGRAMS, WAS AS

6696
04:44:17,529 --> 04:44:19,264
A FORUM AT NATIONAL ACADEMIES

6697
04:44:19,264 --> 04:44:21,600
TWO WEEKS AGO ON REGENERATIVE

6698
04:44:21,600 --> 04:44:22,601
MEDICINE, PARTICULARLY

6699
04:44:22,601 --> 04:44:23,635
MANUFACTURING CHALLENGES IN

6700
04:44:23,635 --> 04:44:24,469
REGENERATIVE MEDICINE.

6701
04:44:24,469 --> 04:44:27,038
WE ALSO TO KICK OFF THIS DESIGN

6702
04:44:27,038 --> 04:44:29,574
EFFORT, THE FOUNDATION PUT OUT

6703
04:44:29,574 --> 04:44:32,077
AN RFI IN SEPTEMBER ASKING FOR

6704
04:44:32,077 --> 04:44:33,745
INFORMATION FROM THE STAKEHOLDER

6705
04:44:33,745 --> 04:44:35,046
COMMUNITIES ABOUT THE CELL-BASED

6706
04:44:35,046 --> 04:44:36,815
THERAPY APPROACH AND WHAT TYPES

6707
04:44:36,815 --> 04:44:39,284
OF MODELS, WHAT TYPES OF

6708
04:44:39,284 --> 04:44:40,952
QUESTIONS, WHAT CHALLENGES, ROAD

6709
04:44:40,952 --> 04:44:41,853
BLOCKS, POTENTIAL SOLUTIONS

6710
04:44:41,853 --> 04:44:46,558
COULD BE ADDRESSED WITHIN THIS

6711
04:44:46,558 --> 04:44:48,760
TYPE OF CONSORTIUM.

6712
04:44:48,760 --> 04:44:50,795
PULLING TOGETHER WHAT WE HOPE

6713
04:44:50,795 --> 04:44:52,163
WILL BE OBJECTIVES OF THE

6714
04:44:52,163 --> 04:44:53,365
RESEARCH PLAN WOULD LIKE TO

6715
04:44:53,365 --> 04:44:56,334
LEVERAGE THE WORK IN THE BESPOKE

6716
04:44:56,334 --> 04:44:57,736
THERAPY CONSORTIUM AS A MODEL

6717
04:44:57,736 --> 04:44:59,504
FOR THE INFRASTRUCTURE THAT WILL

6718
04:44:59,504 --> 04:45:03,942
GO INTO THE RESEARCH PLAN 

6719
04:45:03,942 --> 04:45:06,278
BECAUSE WE'VE DONE A LOT OF WORK

6720
04:45:06,278 --> 04:45:07,145
WITH A LOT OF LESSONS LEARNED

6721
04:45:07,145 --> 04:45:10,749
FROM THE FISHES TWO YEARS OF THE

6722
04:45:10,749 --> 04:45:14,019
BGCT, WE HOPE THAT WILL

6723
04:45:14,019 --> 04:45:15,253
ACCELERATE A DESIGN PHASE.

6724
04:45:15,253 --> 04:45:18,089
WE START WITH A CONCEPT THAT'S

6725
04:45:18,089 --> 04:45:19,090
APPROVED BY RELEVANT EXECUTIVE

6726
04:45:19,090 --> 04:45:22,661
BODY, THAT TAKES US INTO BETWEEN

6727
04:45:22,661 --> 04:45:25,263
SIX TO TWELVE-MONTH DESIGN PHASE

6728
04:45:25,263 --> 04:45:26,431
THAT CULMINATES IN RESEARCH PLAN

6729
04:45:26,431 --> 04:45:28,300
WE USE TO SECURE COMMITMENTS AND

6730
04:45:28,300 --> 04:45:30,702
EXECUTE ON THE PROJECT.

6731
04:45:30,702 --> 04:45:36,374
BECAUSE OF THE BGTC AND WORK

6732
04:45:36,374 --> 04:45:38,576
THAT'S BEEN ACCOMPLISHED WE HAVE

6733
04:45:38,576 --> 04:45:40,211
WORK TO GET THROUGH THE GATE

6734
04:45:40,211 --> 04:45:41,846
QUICKLY, FOCUSING EFFORTS ON THE

6735
04:45:41,846 --> 04:45:43,248
TWO-DAY WORKSHOP BUILDING OUT

6736
04:45:43,248 --> 04:45:47,152
THAT DRAFT OF THE RESEARCH PLAN.

6737
04:45:47,152 --> 04:45:51,489
WE EXPECT SOME FOCUS ON BASIC

6738
04:45:51,489 --> 04:45:53,024
BIOLOGY AND UNDERSTANDING HOW

6739
04:45:53,024 --> 04:45:55,093
THAT APPLIES TO TARGETED

6740
04:45:55,093 --> 04:45:56,628
THERAPIES, BUT IN PARTICULAR

6741
04:45:56,628 --> 04:46:01,333
FOCUSING ON THAT PRE-CLINICAL 

6742
04:46:01,333 --> 04:46:02,867
AND PRODUCT TESTING PIPELINE,

6743
04:46:02,867 --> 04:46:05,804
SELECTING ZIGSES AS PROVE OF

6744
04:46:05,804 --> 04:46:10,275
CONSENT AND EXECUTING ON PHASE

6745
04:46:10,275 --> 04:46:14,446
1-2 CLINICAL TRIALS TO SHOW A

6746
04:46:14,446 --> 04:46:15,547
STREAMLINED DEVELOPMENT IS

6747
04:46:15,547 --> 04:46:15,814
FEASIBLE.

6748
04:46:15,814 --> 04:46:16,781
STARTING TO OVERSOME SOME

6749
04:46:16,781 --> 04:46:18,950
BARRIERS THAT CAN HELP MOVE THE

6750
04:46:18,950 --> 04:46:22,220
FIELD FORWARD AND THEN ALSO LIKE

6751
04:46:22,220 --> 04:46:23,421
THE BGTC IN COMPLIANCE WITH

6752
04:46:23,421 --> 04:46:25,523
GOALS OF THE AMP PROGRAM

6753
04:46:25,523 --> 04:46:27,058
GENERATING A PLAY BOOK THAT

6754
04:46:27,058 --> 04:46:31,096
WOULD BE MADE PUBLICLY

6755
04:46:31,096 --> 04:46:31,596
ACCESSIBLE AND REUSABLE

6756
04:46:31,596 --> 04:46:33,431
INFORMATION IN TERMS OF

6757
04:46:33,431 --> 04:46:35,400
PROTOCOL, REGULATORY TEMPLATES

6758
04:46:35,400 --> 04:46:37,469
THAT WILL HELP INFORM OTHER

6759
04:46:37,469 --> 04:46:38,670
THERAPY DEVELOPMENTS OUTSIDE OF

6760
04:46:38,670 --> 04:46:43,174
THE ONES THAT ARE SELECTED FOR

6761
04:46:43,174 --> 04:46:46,678
THIS CONSORTIUM.

6762
04:46:46,678 --> 04:46:54,018
THIS IS THE BGCT MODEL, TOPLINE 

6763
04:46:54,018 --> 04:46:55,987
BEING BASIC BIOLOGY OF AAV, ONE

6764
04:46:55,987 --> 04:46:57,756
THING WE'LL DISCUSS IS ALIGNING

6765
04:46:57,756 --> 04:47:00,158
ON MODEL FOR CONSORTIUM TO FOCUS

6766
04:47:00,158 --> 04:47:01,793
ON.

6767
04:47:01,793 --> 04:47:04,462
SO LIKE THE BESPOKE GENE

6768
04:47:04,462 --> 04:47:09,534
CONSORTIUM FOCUSED ON AAV GENE

6769
04:47:09,534 --> 04:47:10,668
REPLACEMENT TECHNOLOGY, CELL

6770
04:47:10,668 --> 04:47:12,737
BASED CONSORTIUM WILL NEED TO

6771
04:47:12,737 --> 04:47:15,039
SELECT A NARROW PATH BAY.

6772
04:47:15,039 --> 04:47:17,976
BGCT HAS TWO TRACKS IN THE

6773
04:47:17,976 --> 04:47:20,078
RESEARCH ASPECT, ONE ON

6774
04:47:20,078 --> 04:47:20,712
ENHANCING VECTOR GENERATION,

6775
04:47:20,712 --> 04:47:23,047
MORE TARGETED AT THE INFORMATION

6776
04:47:23,047 --> 04:47:25,417
PROCESSES, AND ONE THAT'S

6777
04:47:25,417 --> 04:47:26,885
FOCUSED ON ENHANCING GENE

6778
04:47:26,885 --> 04:47:29,154
EXPRESSION IN A PATIENT, MORE

6779
04:47:29,154 --> 04:47:30,455
TARGETED TO CLINICAL OUTCOMES.

6780
04:47:30,455 --> 04:47:33,425
BUT BOTH OF THOSE HAVE THE GOAL

6781
04:47:33,425 --> 04:47:34,726
OF PROVIDING A BETTER

6782
04:47:34,726 --> 04:47:36,828
UNDERSTANDING OF THE AAV BASIC

6783
04:47:36,828 --> 04:47:38,997
BIOLOGY THAT CAN TRANSLATE INTO

6784
04:47:38,997 --> 04:47:40,865
INCREASED EFFICIENCY OF THE

6785
04:47:40,865 --> 04:47:43,401
PRODUCTION AND USE OF AAV GENE

6786
04:47:43,401 --> 04:47:43,935
THERAPIES.

6787
04:47:43,935 --> 04:47:46,438
THE CRUX OF THE PROJECT THOUGH

6788
04:47:46,438 --> 04:47:48,573
IS THE CLINICAL PIPELINE.

6789
04:47:48,573 --> 04:47:49,974
WE STARTED OUT COMPLETELY WITH A

6790
04:47:49,974 --> 04:47:52,977
BLANK PIECE OF PAPER AS TO WHAT

6791
04:47:52,977 --> 04:47:55,947
DISEASES WOULD BE INCLUDED.

6792
04:47:55,947 --> 04:47:58,917
DID A BIPHASE COLLECTION THAT

6793
04:47:58,917 --> 04:48:01,019
STARTED OFF WITH INITIAL

6794
04:48:01,019 --> 04:48:01,786
SUBMISSION, DOWN SELECTION,

6795
04:48:01,786 --> 04:48:03,254
REQUEST FOR CLINICAL TRIAL

6796
04:48:03,254 --> 04:48:03,788
PROPOSALS.

6797
04:48:03,788 --> 04:48:05,924
ULTIMATELY LANDED ON A PORTFOLIO

6798
04:48:05,924 --> 04:48:10,762
OF EIGHT DISEASES THAT WE'LL BE

6799
04:48:10,762 --> 04:48:11,629
TAKING THROUGH MANUFACTURING

6800
04:48:11,629 --> 04:48:16,000
WITH CRITICAL QUALITY ATTRIBUTE,

6801
04:48:16,000 --> 04:48:16,801
PRE-CLINICAL TESTING PROTOCOLS

6802
04:48:16,801 --> 04:48:20,438
ON THE BASIS OF ROUTES OF

6803
04:48:20,438 --> 04:48:22,040
ADMINISTRATION, AND THEN INTO

6804
04:48:22,040 --> 04:48:25,510
PHASE 1 TRIAL USING A VERY

6805
04:48:25,510 --> 04:48:27,812
TEMPLATED SET OF REGULATORY

6806
04:48:27,812 --> 04:48:29,814
SUBMISSIONS, ALL MADE PUBLICLY

6807
04:48:29,814 --> 04:48:32,550
AVAILABLE SO OTHERS CAN USE THE

6808
04:48:32,550 --> 04:48:32,917
SAME FRAMEWORK.

6809
04:48:32,917 --> 04:48:35,620
AND SO YOU CAN IMAGINE A

6810
04:48:35,620 --> 04:48:36,955
CELL-BASED THERAPY CONSORTIUM

6811
04:48:36,955 --> 04:48:39,324
COULD LOOK SIMILAR TO THE WORK

6812
04:48:39,324 --> 04:48:42,727
THAT THE THE BGCT FRAMEWORK HAS

6813
04:48:42,727 --> 04:48:44,162
ESTABLISHED, POTENTIAL FOCUS ON

6814
04:48:44,162 --> 04:48:47,232
SOME BASIC BIOLOGY AND

6815
04:48:47,232 --> 04:48:48,900
TRANSLATIONAL IMPLICATION IN

6816
04:48:48,900 --> 04:48:51,369
ENHANCING TISSUE DELIVERY AND

6817
04:48:51,369 --> 04:48:53,738
INCORPORATION IN LOOKING AT

6818
04:48:53,738 --> 04:48:55,240
ALLOGENEIC VERSUS AUTOLOGOUS

6819
04:48:55,240 --> 04:48:55,773
MODELS.

6820
04:48:55,773 --> 04:48:58,510
AND THEN SIMILARLY CREATING THAT

6821
04:48:58,510 --> 04:48:59,577
END-TO-END MANUFACTURING

6822
04:48:59,577 --> 04:49:01,112
PRE-CLINICAL TESTING AND

6823
04:49:01,112 --> 04:49:02,914
CLINICAL TREATMENT PIPELINE THAT

6824
04:49:02,914 --> 04:49:04,415
CAN SERVE AS PROOF-OF-CONCEPT

6825
04:49:04,415 --> 04:49:05,650
FOR FUTURE USE.

6826
04:49:05,650 --> 04:49:08,486
AND SO THE CONCEPT OF THIS

6827
04:49:08,486 --> 04:49:10,121
CONSORTIUM WAS APPROVED ABOUT

6828
04:49:10,121 --> 04:49:12,190
TEN DAYS AGO, SO REPLACEMENT

6829
04:49:12,190 --> 04:49:13,825
EXCITED TO START TO BUILD OUT

6830
04:49:13,825 --> 04:49:15,159
THAT RESEARCH PLAN.

6831
04:49:15,159 --> 04:49:18,563
AND IN TERMS OF TIMING WE'RE

6832
04:49:18,563 --> 04:49:20,431
HOPING THAT WE'LL BE ABLE TO

6833
04:49:20,431 --> 04:49:23,268
FINALIZE THE RESEARCH PLAN FOR

6834
04:49:23,268 --> 04:49:24,602
THIS CONSORTIUM FAIRLY QUICKLY.

6835
04:49:24,602 --> 04:49:28,540
WE HOPE TO PRESENT THAT TO THE

6836
04:49:28,540 --> 04:49:33,177
AMP EXECUTIVE COMMITTEE FOR

6837
04:49:33,177 --> 04:49:36,047
APPROVAL IN MID-DISEASE,

6838
04:49:36,047 --> 04:49:39,884
AUTHORIZATION FOR  FNIH TO BEGIN

6839
04:49:39,884 --> 04:49:42,053
FUNDRAISING, POTENTIALLY

6840
04:49:42,053 --> 04:49:43,321
LAUNCHING IN MID-2024.

6841
04:49:43,321 --> 04:49:45,723
WE THINK DELIVERABLES WOULD BE

6842
04:49:45,723 --> 04:49:56,267
OPTIMIZED BIOLOGY OF ONE OR TWO 

6843
04:49:59,203 --> 04:50:00,672
CELL-BASED THERAPY MODALITIES,

6844
04:50:00,672 --> 04:50:01,673
DEFINING TESTING, ESTABLISHING

6845
04:50:01,673 --> 04:50:03,241
THAT PLAY BOOK THAT PUTS THE

6846
04:50:03,241 --> 04:50:04,242
LEARNINGS OUT INTO THE GENERAL

6847
04:50:04,242 --> 04:50:05,443
PUBLIC.

6848
04:50:05,443 --> 04:50:08,646
AND THAT'S MY LAST SLIDE.

6849
04:50:08,646 --> 04:50:11,282
REALLY EXCITED TO CONTINUE THE

6850
04:50:11,282 --> 04:50:12,483
DISCUSSION AND LOOKING FORWARD

6851
04:50:12,483 --> 04:50:13,685
TO HEARING THE OTHER COMMENTS

6852
04:50:13,685 --> 04:50:17,221
AND INPUTS FROM THE GROUP.

6853
04:50:17,221 --> 04:50:27,365
THANKS. 

6854
04:50:44,882 --> 04:50:47,885
>> KRISHENDU ROY AND
JOHNNY

6855
04:50:47,885 --> 04:50:51,489
HUARD WERE GOING TO MODERATE.

6856
04:50:51,489 --> 04:50:54,525
KRISHENDU ROY WAS UNABLE TO

6857
04:50:54,525 --> 04:50:55,326
TRAVEL, HE'S ONLINE.

6858
04:50:55,326 --> 04:50:57,095
WE'LL GET INTO THE DISCUSSION

6859
04:50:57,095 --> 04:50:59,397
PHASE.

6860
04:50:59,397 --> 04:51:05,370
 

6861
04:51:05,370 --> 04:51:14,779
 

6862
04:51:14,779 --> 04:51:18,282
KRISH GOES FIRST.

6863
04:51:18,282 --> 04:51:24,722
AND THEN -- OKAY.

6864
04:51:24,722 --> 04:51:25,690
SO KRISH, YOUR SLIDE'S UP, WE

6865
04:51:25,690 --> 04:51:30,762
MIGHT BE ABLE TO SEE YOU IN THE

6866
04:51:30,762 --> 04:51:31,062
LITTLE BOX.

6867
04:51:31,062 --> 04:51:32,697
>> ARE MY SLIDES UP?

6868
04:51:32,697 --> 04:51:33,931
I CAN'T SEE MY SLIDES.

6869
04:51:33,931 --> 04:51:37,435
>> YES, YOUR SLIDES ARE
UP.

6870
04:51:37,435 --> 04:51:45,643
 

6871
04:51:45,643 --> 04:51:47,945
>> EXCELLENT.

6872
04:51:47,945 --> 04:51:48,312
THANK YOU, BOB.

6873
04:51:48,312 --> 04:51:49,781
THANK YOU, EVERYBODY.

6874
04:51:49,781 --> 04:51:52,050
I'M SORRY I COULDN'T BE THERE

6875
04:51:52,050 --> 04:51:52,250
TODAY.

6876
04:51:52,250 --> 04:51:56,220
SO, I'M JUST GOING TO START OFF

6877
04:51:56,220 --> 04:51:58,456
WITH REALLY THINKING ABOUT THE

6878
04:51:58,456 --> 04:52:01,192
MANUFACTURING CHALLENGE THAT YOU

6879
04:52:01,192 --> 04:52:05,963
JUST HEARD ABOUT.

6880
04:52:05,963 --> 04:52:07,932
AND GIVEN THE PLATFORM

6881
04:52:07,932 --> 04:52:11,569
TECHNOLOGIES ARE SOMEWHAT

6882
04:52:11,569 --> 04:52:12,737
DISEASE AGNOSTIC AND THERAPY

6883
04:52:12,737 --> 04:52:15,173
AGNOSTIC I THINK MANUFACTURING

6884
04:52:15,173 --> 04:52:18,409
IS PROBABLY A VERY STRONG

6885
04:52:18,409 --> 04:52:20,678
CHALLENGE TO ADDRESS.

6886
04:52:20,678 --> 04:52:21,913
AND I'M CURRENTLY AT VANDERBILT,

6887
04:52:21,913 --> 04:52:26,384
BUT MOST OF WHAT I'LL TALK ABOUT

6888
04:52:26,384 --> 04:52:29,620
TODAY COMES FROM -- NEXT SLIDE

6889
04:52:29,620 --> 04:52:32,356
PLEASE -- COMES FROM THE NSF

6890
04:52:32,356 --> 04:52:33,758
ENGINEERING RESEARCH CENTER THAT

6891
04:52:33,758 --> 04:52:34,292
I USE.

6892
04:52:34,292 --> 04:52:41,499
I CAN GET THE NEXT SLIDE?

6893
04:52:41,499 --> 04:52:43,935
GREAT, THANK YOU.

6894
04:52:43,935 --> 04:52:47,872
YOU CAN CLICK THROUGH IT.

6895
04:52:47,872 --> 04:52:48,039
YES.

6896
04:52:48,039 --> 04:52:49,807
SO, COMES FROM THE TWO LARGE

6897
04:52:49,807 --> 04:52:52,076
RESEARCH CENTERS THAT I HAVE THE

6898
04:52:52,076 --> 04:52:54,212
PRIVILEGE OF LEADING OVER THE

6899
04:52:54,212 --> 04:52:57,048
LAST SIX, SEVEN YEARS NOW.

6900
04:52:57,048 --> 04:53:00,551
ONE BEING THE NSF ERC, CELL

6901
04:53:00,551 --> 04:53:01,986
MANUFACTURING TECHNOLOGIES, AND

6902
04:53:01,986 --> 04:53:04,522
THE OTHER BEING THE MARKET

6903
04:53:04,522 --> 04:53:08,059
CENTER FOR CELL CHARACTERIZATION

6904
04:53:08,059 --> 04:53:12,063
MANUFACTURING, WHICH ARE 

6905
04:53:12,063 --> 04:53:12,597
MULTI-UNIVERSITY NATIONAL,

6906
04:53:12,597 --> 04:53:13,231
INTERNATIONAL CENTERS, AND NOT

6907
04:53:13,231 --> 04:53:16,000
JUST IN THE U.S. BUT ALSO OTHER

6908
04:53:16,000 --> 04:53:18,202
UNIVERSITIES AND INSTITUTIONS IN

6909
04:53:18,202 --> 04:53:19,971
JAPAN AND CANADA AND IRELAND.

6910
04:53:19,971 --> 04:53:23,708
THAT HAS BEEN LASER FOCUSED ON

6911
04:53:23,708 --> 04:53:27,979
DEVELOPING TECHNOLOGIES AND 

6912
04:53:27,979 --> 04:53:29,914
PLATFORMS FOR CELL THERAPIES,

6913
04:53:29,914 --> 04:53:31,449
INCLUDING FUNDING FROM NIH IDCC

6914
04:53:31,449 --> 04:53:33,618
HUB WHICH I'LL TALK ABOUT IN A

6915
04:53:33,618 --> 04:53:36,821
SECOND, AS WELL AS SEVERAL

6916
04:53:36,821 --> 04:53:45,196
PROJECTS FROM FDA CBER.

6917
04:53:45,196 --> 04:53:45,663
NEXT SLIDE.

6918
04:53:45,663 --> 04:53:48,232
SO, I THINK IF WE STEP BACK AND

6919
04:53:48,232 --> 04:53:52,403
THINK OF CELL-BASED THERAPIES

6920
04:53:52,403 --> 04:53:55,706
AND TISSUE-BASED THERAPIES, WE

6921
04:53:55,706 --> 04:53:57,041
IN VERY INTERESTING PRODUCT

6922
04:53:57,041 --> 04:54:01,946
REALM THAT DOES NOT REALLY

6923
04:54:01,946 --> 04:54:02,380
FOLLOW OUR CLASSICAL

6924
04:54:02,380 --> 04:54:03,915
BIOMANUFACTURING PARADIGM.

6925
04:54:03,915 --> 04:54:07,652
YOU HAVE AN INCREDIBLY VARIABLE

6926
04:54:07,652 --> 04:54:09,153
STARTING MATERIAL, EVEN FOR

6927
04:54:09,153 --> 04:54:10,021
ALLOGENEIC.

6928
04:54:10,021 --> 04:54:11,989
I THINK PEOPLE ARE INCREASINGLY

6929
04:54:11,989 --> 04:54:13,424
UNDERSTANDING THAT JUST BECAUSE

6930
04:54:13,424 --> 04:54:16,594
YOU HAVE A MASTER CELL BANK, YOU

6931
04:54:16,594 --> 04:54:18,763
MAKE AN iPSC CELL BANK, YOU'RE

6932
04:54:18,763 --> 04:54:20,097
NOT GOING TO GET THE SAME

6933
04:54:20,097 --> 04:54:22,266
STARTING MATERIAL TO MAKE YOUR

6934
04:54:22,266 --> 04:54:26,003
END PRODUCT ALL THE TIME.

6935
04:54:26,003 --> 04:54:28,773
CELLULAR DIFFERENTIATION IS BY

6936
04:54:28,773 --> 04:54:30,641
NATURE A STOCHASTIC PROCESS.

6937
04:54:30,641 --> 04:54:33,144
WE PUT THAT INTO A FIXED PROCESS

6938
04:54:33,144 --> 04:54:37,315
MANUFACTURING WITH MANY 

6939
04:54:37,315 --> 04:54:38,282
DIFFERENT PARAMETERS, AND OUT

6940
04:54:38,282 --> 04:54:40,885
COMES A PROJECT WITH A THOUSAND

6941
04:54:40,885 --> 04:54:43,621
OR TWO THOUSAND BIOACTIVE

6942
04:54:43,621 --> 04:54:48,125
MOLECULES OF RNA PROTEINS, DNA 

6943
04:54:48,125 --> 04:54:49,527
LIPIDS, METABOLITES, MANY OF

6944
04:54:49,527 --> 04:54:51,295
WHICHED FDA WOULD HAVE

6945
04:54:51,295 --> 04:54:52,930
CONSIDERED A DRUG, AND WE'RE

6946
04:54:52,930 --> 04:54:57,969
INJECTING THAT INTO A PATIENT, A

6947
04:54:57,969 --> 04:55:00,671
LIVING DRUG WHICH GETS MODIFIED

6948
04:55:00,671 --> 04:55:04,308
BY THE PATIENT'S DISEASE STATUS,

6949
04:55:04,308 --> 04:55:05,443
IMMUNE SYSTEM, PRIOR TEAMS,

6950
04:55:05,443 --> 04:55:06,844
MICROENVIRONMENTED IN THE

6951
04:55:06,844 --> 04:55:07,078
PATIENT.

6952
04:55:07,078 --> 04:55:10,514
HOW DO WE PREDICT FUNCTION, HOW

6953
04:55:10,514 --> 04:55:13,651
DO WE PREDICT CRITICAL QUALITY

6954
04:55:13,651 --> 04:55:15,519
ATTRIBUTES IS THE TREMENDOUS

6955
04:55:15,519 --> 04:55:17,154
CHALLENGE IN CELL THERAPY, MUCH

6956
04:55:17,154 --> 04:55:22,360
MORE THAN GENE THERAPY VECTORS,

6957
04:55:22,360 --> 04:55:24,929
MUCH MORE THAN MONOCLONAL

6958
04:55:24,929 --> 04:55:26,364
ANTIBODY, PROTEIN THERAPEUTICS

6959
04:55:26,364 --> 04:55:28,099
OR COMPLEX THERAPIES WE'VE EVER

6960
04:55:28,099 --> 04:55:31,269
MANUFACTURED, AND BECAUSE IT IS

6961
04:55:31,269 --> 04:55:34,272
A COMPLETELY VARYING AND DYNAMIC

6962
04:55:34,272 --> 04:55:34,572
MATERIAL.

6963
04:55:34,572 --> 04:55:37,642
NEXT SLIDE PLEASE.

6964
04:55:37,642 --> 04:55:40,711
SO, WE HAVE BEEN THINKING ABOUT

6965
04:55:40,711 --> 04:55:42,546
SO MANY UNANSWERED QUESTIONS

6966
04:55:42,546 --> 04:55:46,117
THAT I THINK AS A CONSORTIUM WE

6967
04:55:46,117 --> 04:55:47,084
COULD START ADDRESSING, FIRST OF

6968
04:55:47,084 --> 04:55:51,122
ALL I THINK IF YOU ASK ANYONE IN

6969
04:55:51,122 --> 04:55:52,423
THE CELL THERAPY INDUSTRY WHAT

6970
04:55:52,423 --> 04:55:54,058
ARE YOUR BIG CHALLENGES EVERYONE

6971
04:55:54,058 --> 04:55:57,995
WOULD AGREE THAT WE DO NOT KNOW

6972
04:55:57,995 --> 04:56:01,632
WHAT QUALITY MEANS IN CELL TERP.

6973
04:56:01,632 --> 04:56:05,002
AS A RESULT, PROCESS PARAMETERS

6974
04:56:05,002 --> 04:56:06,637
THAT CONTROL AND MECHANISM OF

6975
04:56:06,637 --> 04:56:08,239
ACTION LARGELY ARE UNKNOWN AND I

6976
04:56:08,239 --> 04:56:11,542
WOULD ARGUE THAT IT IS EVEN

6977
04:56:11,542 --> 04:56:15,079
LARGELY UNKNOWN FOR CAR T CELL

6978
04:56:15,079 --> 04:56:16,514
THERAPY WHICH WE HAVE SUCCESS

6979
04:56:16,514 --> 04:56:18,382
WITH THE LAST THREE OR FOUR

6980
04:56:18,382 --> 04:56:20,217
YEARS, EVEN THOUGH PATIENTS ARE

6981
04:56:20,217 --> 04:56:21,652
GETTING CURED, WE'RE YET TO

6982
04:56:21,652 --> 04:56:24,588
UNCOVER EXACTLY WHICH SUBSET OF

6983
04:56:24,588 --> 04:56:28,259
POPULATION THAT GIVES LONG-TERM

6984
04:56:28,259 --> 04:56:32,496
DURABLE RESPONSE, ANY CELL

6985
04:56:32,496 --> 04:56:35,566
THERAPY INCLUDING CAR T CELL,

6986
04:56:35,566 --> 04:56:38,402
HOW DO I CONTROL PROCESS

6987
04:56:38,402 --> 04:56:40,237
PARAMETERS AND MAKE SURE EVERY

6988
04:56:40,237 --> 04:56:46,610
BATCH ANYWHERE IN THE WORLD I 

6989
04:56:46,610 --> 04:56:48,245
GET EQUIVALENT QUALITY OF

6990
04:56:48,245 --> 04:56:48,813
PRODUCT.

6991
04:56:48,813 --> 04:56:51,449
WE DON'T KNOW WHY SOME RESPOND,

6992
04:56:51,449 --> 04:56:52,984
OTHER RELAPSE, SOME DON'T

6993
04:56:52,984 --> 04:56:53,851
RESPOND, HOW DO WE PREDICT

6994
04:56:53,851 --> 04:56:55,953
WHETHER A PATIENT IS GOING TO

6995
04:56:55,953 --> 04:56:57,955
RESPOND OR NOT RESPOND?

6996
04:56:57,955 --> 04:57:00,524
WHICH ARE SOME OF THE BASIC

6997
04:57:00,524 --> 04:57:01,826
BIOLOGY QUESTIONS THAT WE HAVE

6998
04:57:01,826 --> 04:57:05,096
NOT YET BEEN ABLE TO UNDERSTAND

6999
04:57:05,096 --> 04:57:06,964
IN CELL THERAPIES, BECAUSE IT'S

7000
04:57:06,964 --> 04:57:10,668
SUCH A COMPLEX PRODUCT AND

7001
04:57:10,668 --> 04:57:12,436
PROCESS.

7002
04:57:12,436 --> 04:57:14,071
NEXT SLIDE PLEASE.

7003
04:57:14,071 --> 04:57:15,706
AND ALL OF THESE ALIGN VERY WELL

7004
04:57:15,706 --> 04:57:18,909
WITH THE U.S. NATIONAL STRATEGY

7005
04:57:18,909 --> 04:57:21,412
FOR ADVANCED MANUFACTURING, THE

7006
04:57:21,412 --> 04:57:31,889
BOLD GOALS RELEASED BY OSTP.

7007
04:57:32,623 --> 04:57:35,860
IF YOU LOOK AT MANUFACTURING,

7008
04:57:35,860 --> 04:57:37,928
GENE EDITING TECHNOLOGIES, THESE

7009
04:57:37,928 --> 04:57:40,865
ALL SQUARE VERY, VERY WELL WITH

7010
04:57:40,865 --> 04:57:43,834
THE CELL THERAPY CELL

7011
04:57:43,834 --> 04:57:46,037
BIOMANUFACTURING PROCESS AND THE

7012
04:57:46,037 --> 04:57:47,671
WHOLE ECOSYSTEM.

7013
04:57:47,671 --> 04:57:50,508
SO I THINK ANY EFFORT THAT WE

7014
04:57:50,508 --> 04:57:54,211
MAKE AT NIH OR FNIH, IT IS GOING

7015
04:57:54,211 --> 04:57:55,913
TO BE WELL ALIGNED WITH OUR

7016
04:57:55,913 --> 04:57:58,049
NATIONAL PRIORITIES.

7017
04:57:58,049 --> 04:58:00,251
NEXT SLIDE PLEASE.

7018
04:58:00,251 --> 04:58:07,458
SO, THIS IS SORT OF THE VISION

7019
04:58:07,458 --> 04:58:09,960
THAT AT THE NSF ERC HAVE TO

7020
04:58:09,960 --> 04:58:11,829
THINK ABOUT CELL THERAPIES.

7021
04:58:11,829 --> 04:58:15,666
FOR US TO CREATE A CONSIST DENT

7022
04:58:15,666 --> 04:58:17,301
REPRODUCIBLE PRODUCT EVERY TIME

7023
04:58:17,301 --> 04:58:19,837
WE MANUFACTURE, WE NEED TO BE

7024
04:58:19,837 --> 04:58:21,572
ABLE TO MEASURE QUALITY IN LINE

7025
04:58:21,572 --> 04:58:24,241
OR AT LINE IN REAL TIME.

7026
04:58:24,241 --> 04:58:27,945
I DO NOT SEE A WAY AROUND IT,

7027
04:58:27,945 --> 04:58:29,914
BECAUSE OF THE VARIABILITY OF

7028
04:58:29,914 --> 04:58:32,983
CELLS AND TISSUES AND THEIR

7029
04:58:32,983 --> 04:58:35,286
PROCESSES, UNLESS WE INTEGRATE

7030
04:58:35,286 --> 04:58:36,320
MEASUREMENTS AND CONTROL THE

7031
04:58:36,320 --> 04:58:38,589
PROCESS TO GET TO A FIXED

7032
04:58:38,589 --> 04:58:41,125
QUALITY PRODUCT OR CLOSE TO A

7033
04:58:41,125 --> 04:58:43,294
FIXED QUALITY PRODUCT, EVERY

7034
04:58:43,294 --> 04:58:44,695
TIME WE MANUFACTURE SOMETHING

7035
04:58:44,695 --> 04:58:47,131
WE'RE GOING TO GET A DIFFERENT

7036
04:58:47,131 --> 04:58:48,766
QUALITY PRODUCT.

7037
04:58:48,766 --> 04:58:51,068
JUST THE PHYSICS OF IT, THE

7038
04:58:51,068 --> 04:58:52,403
MATH, THE BIOLOGY OF IT,

7039
04:58:52,403 --> 04:58:55,272
DICTATES THAT.

7040
04:58:55,272 --> 04:58:56,774
SO FOR US IT'S CELL THERAPY

7041
04:58:56,774 --> 04:58:59,743
PROCESS NEEDS TO BE CLOSED LOOP

7042
04:58:59,743 --> 04:59:01,979
AUTOMATION SYSTEMS, THAT HAS

7043
04:59:01,979 --> 04:59:04,315
MULTIPLE DIFFERENT SENSORS

7044
04:59:04,315 --> 04:59:05,449
AND/OR PROCESS PARAMETER

7045
04:59:05,449 --> 04:59:07,952
MEASUREMENTS THAT ALLOWS US TO

7046
04:59:07,952 --> 04:59:10,054
UNDERSTAND THE PROCESS, THE

7047
04:59:10,054 --> 04:59:14,525
STATUS OF THE PRODUCT, AND

7048
04:59:14,525 --> 04:59:18,229
CONTROL THE PROCESS TO GET TO

7049
04:59:18,229 --> 04:59:20,531
EQUIVALENT OR CONTROLLED PRODUCT

7050
04:59:20,531 --> 04:59:20,865
QUALITY.

7051
04:59:20,865 --> 04:59:23,267
AND LAID UPON THAT IS THIS IDEA

7052
04:59:23,267 --> 04:59:26,237
OF THE SUPPLY CHAIN AND

7053
04:59:26,237 --> 04:59:28,439
LOGISTICS WHICH OFTEN WE IGNORE

7054
04:59:28,439 --> 04:59:31,242
BUT YOU CANNOT BECAUSE AGAIN

7055
04:59:31,242 --> 04:59:34,245
THAT IS GOING TO BE ONE OF THE

7056
04:59:34,245 --> 04:59:36,113
BIGGEST BOTTLENECKS DELIVERING

7057
04:59:36,113 --> 04:59:39,583
THERAPIES TO THE MASSES, WHETHER

7058
04:59:39,583 --> 04:59:42,219
YOU THINK ABOUT CENTRALIZED

7059
04:59:42,219 --> 04:59:43,521
VERSUS REGIONAL VERSUS

7060
04:59:43,521 --> 04:59:44,255
DECENTRALIZED DISTRIBUTED

7061
04:59:44,255 --> 04:59:52,062
MANUFACTURING, ONE NEEDS TO

7062
04:59:52,062 --> 04:59:56,667
THINK ABOUT IMPLEMENTATION OF

7063
04:59:56,667 --> 04:59:58,569
QUEUES THERAPIES, WHO GETS

7064
04:59:58,569 --> 05:00:00,304
TREATED FIRST, IN THE QUEUE

7065
05:00:00,304 --> 05:00:00,971
FIRST, SICKEST FIRST, WHO

7066
05:00:00,971 --> 05:00:03,374
DECIDES WHO IS THE SICKEST

7067
05:00:03,374 --> 05:00:03,607
PATIENT?

7068
05:00:03,607 --> 05:00:05,276
THERE ARE A LOT OF ETHICS

7069
05:00:05,276 --> 05:00:09,280
CONCERNED WHERE HE WE HAVE VERY,

7070
05:00:09,280 --> 05:00:10,047
VERY LIMITED MANUFACTURING

7071
05:00:10,047 --> 05:00:11,215
CAPACITY IN THE COUNTRY OR IN

7072
05:00:11,215 --> 05:00:12,683
THE WORLD.

7073
05:00:12,683 --> 05:00:14,652
IF YOU ASK MULTIPLE MYELOMA

7074
05:00:14,652 --> 05:00:17,488
PHYSICIAN TODAY, THEY SAY WE

7075
05:00:17,488 --> 05:00:23,093
HAVE HUNDREDS OF PATIENTS WHO 

7076
05:00:23,093 --> 05:00:25,963
ARE GOING TO DIE, EVEN WITH TWO

7077
05:00:25,963 --> 05:00:27,731
APPROVED MYELOMA CAR T THERAPIES

7078
05:00:27,731 --> 05:00:28,899
THAT ARE FDA APPROVED.

7079
05:00:28,899 --> 05:00:31,335
BUT THEY WILL NOT GET IT BECAUSE

7080
05:00:31,335 --> 05:00:33,304
WE SIMPLY DO NOT HAVE

7081
05:00:33,304 --> 05:00:35,039
MANUFACTURING CAPACITIES.

7082
05:00:35,039 --> 05:00:37,107
AND PLENTY OF HOSPITALS HAVE

7083
05:00:37,107 --> 05:00:38,976
ENOUGH PATIENTS TO PUT ON THE

7084
05:00:38,976 --> 05:00:40,177
LINE, WE DON'T HAVE

7085
05:00:40,177 --> 05:00:41,612
MANUFACTURING CAPACITIES TO DO

7086
05:00:41,612 --> 05:00:42,746
THAT.

7087
05:00:42,746 --> 05:00:46,217
SO WHEN WE THINK ABOUT A LARGE

7088
05:00:46,217 --> 05:00:47,117
NATIONAL EFFORT IN THIS SPACE,

7089
05:00:47,117 --> 05:00:50,387
WE NEED TO THINK ABOUT ALL OF

7090
05:00:50,387 --> 05:00:51,922
THESE CONSIDERATIONS AND SYSTEMS

7091
05:00:51,922 --> 05:00:56,060
APPROACH AND NOT JUST THE

7092
05:00:56,060 --> 05:00:57,761
INDIVIDUAL BIOLOGICAL QUESTION,

7093
05:00:57,761 --> 05:00:58,996
BIOMANUFACTURING QUESTION,

7094
05:00:58,996 --> 05:01:00,030
SUPPLY CHAIN QUESTION, BUT ALL

7095
05:01:00,030 --> 05:01:01,999
OF THEM TOGETHER AS A SYSTEMS

7096
05:01:01,999 --> 05:01:02,366
PROBLEM.

7097
05:01:02,366 --> 05:01:04,969
NEXT SLIDE PLEASE.

7098
05:01:04,969 --> 05:01:06,770
SO, I'M GOING TO VERY QUICKLY GO

7099
05:01:06,770 --> 05:01:08,339
THROUGH A FEW OF THE WORKS WE'VE

7100
05:01:08,339 --> 05:01:09,540
BEEN DOING.

7101
05:01:09,540 --> 05:01:10,874
I GIVE THIS EXAMPLE, OTHERS, A

7102
05:01:10,874 --> 05:01:12,843
LOT OF FOLKS IN THE ROOM HAVE

7103
05:01:12,843 --> 05:01:14,044
SEEN THIS.

7104
05:01:14,044 --> 05:01:20,184
ON THE RIGHT THERE'S TWEETS FROM

7105
05:01:20,184 --> 05:01:21,619
PATRICK HANLEY, LIVE TWEETING

7106
05:01:21,619 --> 05:01:26,523
PETER MARKS A COUPLE YEARS AGO,

7107
05:01:26,523 --> 05:01:28,392
TALKING ABOUT THE CQAs, IN AN

7108
05:01:28,392 --> 05:01:30,694
IDEAL WORLD WE WOULD HAVE

7109
05:01:30,694 --> 05:01:32,896
SUPERCOMPUTERS, TAKES THE DATA,

7110
05:01:32,896 --> 05:01:34,031
FIGURES OUT WHAT CHARACTERISTICS

7111
05:01:34,031 --> 05:01:35,532
ARE ASSOCIATED WITH POSITIVE

7112
05:01:35,532 --> 05:01:35,966
OUTCOME.

7113
05:01:35,966 --> 05:01:38,269
WE'RE STILL WORKING ON THAT BUT

7114
05:01:38,269 --> 05:01:40,337
TAKING MAYBE STEPS TOWARDS THAT.

7115
05:01:40,337 --> 05:01:42,606
SO THERE ARE TWO LARGE

7116
05:01:42,606 --> 05:01:44,508
A.I.-DRIVEN EFFORT WE HAVE IN

7117
05:01:44,508 --> 05:01:46,677
THE NSF CENTER.

7118
05:01:46,677 --> 05:01:48,646
ONE IS CHARACTERIZING CELLS THAT

7119
05:01:48,646 --> 05:01:50,948
ARE GOING INTO PATIENTS TO THE

7120
05:01:50,948 --> 05:01:52,349
FULLEST EXTENT POSSIBLE, BOTH AT

7121
05:01:52,349 --> 05:01:53,550
THE BEGINNING OF THE PROCESS AND

7122
05:01:53,550 --> 05:01:57,187
AT THE END OF THE PROCESS.

7123
05:01:57,187 --> 05:01:58,222
AND PREDICTING PRODUCT QUALITY

7124
05:01:58,222 --> 05:02:00,057
AT THE END OF THE MANUFACTURING.

7125
05:02:00,057 --> 05:02:02,760
AND THEN TAKING THAT PRODUCT,

7126
05:02:02,760 --> 05:02:05,496
CHARACTERIZING THAT, AND LOOKING

7127
05:02:05,496 --> 05:02:08,465
AT PATIENT OUTCOMES AND PATIENT

7128
05:02:08,465 --> 05:02:10,067
VARIABLES TO UNDERSTAND WHAT

7129
05:02:10,067 --> 05:02:12,069
PRODUCT QUALITY IS MOST

7130
05:02:12,069 --> 05:02:16,440
PREDICTIVE OF A POSITIVE PATIENT

7131
05:02:16,440 --> 05:02:17,007
OUTCOME.

7132
05:02:17,007 --> 05:02:18,175
THESE REQUESTS, CLOSE

7133
05:02:18,175 --> 05:02:21,512
PARTNERSHIP WITH CLINICAL

7134
05:02:21,512 --> 05:02:23,647
TRIALS, THESE REQUEST REQUIRE

7135
05:02:23,647 --> 05:02:24,715
CLOSE PARTNERSHIP WITH BIOLOGIST

7136
05:02:24,715 --> 05:02:26,383
AND MANUFACTURING.  WE HAVE A

7137
05:02:26,383 --> 05:02:28,819
NOT DONE CLINICAL TRIALS IN THIS

7138
05:02:28,819 --> 05:02:30,888
COUNTRY WITH THIS GOAL IN MIND

7139
05:02:30,888 --> 05:02:33,624
THAT WE NEED TO CONNECT PRODUCT

7140
05:02:33,624 --> 05:02:34,491
CHARACTERISTICS WITH PATIENT

7141
05:02:34,491 --> 05:02:34,725
OUTCOME.

7142
05:02:34,725 --> 05:02:38,095
THIS IS ONE OF THE BIGGEST

7143
05:02:38,095 --> 05:02:38,896
BOTTLENECKS FOR INDUSTRY BECAUSE

7144
05:02:38,896 --> 05:02:41,165
IF THEY CAN NOT PREDICT OR

7145
05:02:41,165 --> 05:02:43,000
CANNOT BE CONFIDENT THAT A

7146
05:02:43,000 --> 05:02:44,668
PRODUCT THEY MANUFACTURE IS

7147
05:02:44,668 --> 05:02:47,204
GOING TO WORK X AMOUNT OF TIME

7148
05:02:47,204 --> 05:02:49,840
IN A PATIENT POPULATION, IT

7149
05:02:49,840 --> 05:02:50,607
BECOMES A TREMENDOUSLY RISKY

7150
05:02:50,607 --> 05:02:55,079
PRODUCT FOR THEM TO TAKE ON.

7151
05:02:55,079 --> 05:02:56,413
NOT EVERY THERAPEUTIC PRODUCT

7152
05:02:56,413 --> 05:02:59,049
WILL HAVE THE EFFECT SIZE OF A

7153
05:02:59,049 --> 05:03:00,050
CAR T.

7154
05:03:00,050 --> 05:03:05,456
WE NEED TO TAKE A GRIP ON THAT.

7155
05:03:05,456 --> 05:03:08,692
THERE WILL BE MUCH CLOSER

7156
05:03:08,692 --> 05:03:09,660
THERAPEUTIC INDEX AND WE NEED TO

7157
05:03:09,660 --> 05:03:11,295
THINK ABOUT HOW DO WE GET THEM

7158
05:03:11,295 --> 05:03:13,163
INTO A CONFIDENT PRODUCT EVERY

7159
05:03:13,163 --> 05:03:15,099
TIME WE MANUFACTURE IT.

7160
05:03:15,099 --> 05:03:16,133
NEXT SLIDE PLEASE.

7161
05:03:16,133 --> 05:03:17,968
SO, A LOT OF EFFORT THAT WE HAVE

7162
05:03:17,968 --> 05:03:20,604
PUT IN, AND THIS IS NOT NEW TO

7163
05:03:20,604 --> 05:03:22,573
THE CHEMICAL ENGINEERS, WE DO

7164
05:03:22,573 --> 05:03:26,276
THAT IN BIOPROCESSING ALL THE

7165
05:03:26,276 --> 05:03:29,813
TIME, IS TO USE -- DESIGN

7166
05:03:29,813 --> 05:03:31,882
EXPERIMENTS AND MASSIVE PARALLEL

7167
05:03:31,882 --> 05:03:33,083
DESIGN, MULTIOMIC MEASUREMENTS

7168
05:03:33,083 --> 05:03:38,322
OF CELLS AND THE PROCESS, AND

7169
05:03:38,322 --> 05:03:39,089
THEN ITERATIVELY CONTINUOUSLY

7170
05:03:39,089 --> 05:03:40,624
IMPROVE THE PROJECT TILL WE

7171
05:03:40,624 --> 05:03:42,593
UNDERSTAND THE PROCESS DEEP

7172
05:03:42,593 --> 05:03:45,796
ENOUGH TO FIGURE OUT WHAT ARE

7173
05:03:45,796 --> 05:03:49,299
THE PROCESS PARAMETERS THAT 

7174
05:03:49,299 --> 05:03:51,468
CONTROL QUALITY ATTRIBUTES OF

7175
05:03:51,468 --> 05:04:00,110
CELLS AND HOW REPRODUCE 

7176
05:04:00,110 --> 05:04:01,945
REPRODUCIBLY DO THAT.

7177
05:04:01,945 --> 05:04:04,114
YOUR PROBABILITY INCREASES.

7178
05:04:04,114 --> 05:04:08,285
SO, WE HAVE OVER THE YEARS

7179
05:04:08,285 --> 05:04:11,221
THOUGHT ABOUT THIS, THIS IS

7180
05:04:11,221 --> 05:04:11,588
PUBLISHED WORK.

7181
05:04:11,588 --> 05:04:14,758
WE'VE LOOKED AT CAR T, FOR

7182
05:04:14,758 --> 05:04:17,461
EXAMPLE, USING THIS TYPE OF

7183
05:04:17,461 --> 05:04:20,464
MACHINE LEARNING TYPE APPROACHES

7184
05:04:20,464 --> 05:04:23,333
TO MEASURE BOTH METABOLOMICS

7185
05:04:23,333 --> 05:04:25,736
PARAMETERS AND LIPIDOMICS

7186
05:04:25,736 --> 05:04:27,171
PARAMETERS AND TRANSCRIPTOMICS

7187
05:04:27,171 --> 05:04:32,276
PARAMETERS, AND THEN IDENTIFYING

7188
05:04:32,276 --> 05:04:35,279
QUALITY ATTRIBUTES AND PROCESS

7189
05:04:35,279 --> 05:04:37,247
MEASUREMENT ATTRIBUTES THAT

7190
05:04:37,247 --> 05:04:41,819
PREDICTIVE OF END PRODUCT

7191
05:04:41,819 --> 05:04:42,219
QUALITY.

7192
05:04:42,219 --> 05:04:44,354
THAT'S THE LEFT SIDE OF THE

7193
05:04:44,354 --> 05:04:44,755
CARTOON I SHOWED.

7194
05:04:44,755 --> 05:04:46,623
NEXT SLIDE PLEASE.

7195
05:04:46,623 --> 05:04:47,391
WE HAVE PUBLISHED SEVERAL OF

7196
05:04:47,391 --> 05:04:47,858
THESE.

7197
05:04:47,858 --> 05:04:50,694
SO, FOR EXAMPLE, IN A CAR T

7198
05:04:50,694 --> 05:04:52,896
SETTING WE CAN PREDICT WHAT THE

7199
05:04:52,896 --> 05:04:54,965
PRODUCT QUALITY, THE PERCENTAGE

7200
05:04:54,965 --> 05:04:56,733
OF MEMORY T CELLS, TYPES OF

7201
05:04:56,733 --> 05:04:58,502
MEMORY T CELLS THAT WILL BE

7202
05:04:58,502 --> 05:05:02,606
GENERATED AT THE END OF THE

7203
05:05:02,606 --> 05:05:05,809
MANUFACTURING, AT DAY 14 BASED

7204
05:05:05,809 --> 05:05:08,545
ON MA TAP LOMBIC OR SECRET OMIC

7205
05:05:08,545 --> 05:05:09,713
MEASUREMENTS FROM DAY FOUR,

7206
05:05:09,713 --> 05:05:11,849
FIVE, SIX.

7207
05:05:11,849 --> 05:05:19,189
THIS IS CRITICAL, DE-RISKING

7208
05:05:19,189 --> 05:05:22,793
EFFORT FOR MANUFACTURING, MY

7209
05:05:22,793 --> 05:05:23,293
DIFFERENTIATION, PRODUCT

7210
05:05:23,293 --> 05:05:23,994
MANUFACTURING GOING IN THE RIGHT

7211
05:05:23,994 --> 05:05:24,361
DIRECTION.

7212
05:05:24,361 --> 05:05:29,500
IF I UNDERSTAND LIKE WE DO NOW

7213
05:05:29,500 --> 05:05:31,134
FOR iPSC PRODUCT AT FOUR

7214
05:05:31,134 --> 05:05:34,938
WEEKS, SIX WEEKS, EIGHT WEEKS,

7215
05:05:34,938 --> 05:05:36,306
I'VE JUST WASTED $5 MILLION, $2

7216
05:05:36,306 --> 05:05:37,875
MILLION, $10 MILLION IN

7217
05:05:37,875 --> 05:05:45,682
MANUFACTURING PROCESS FOR A

7218
05:05:45,682 --> 05:05:49,620
FAILED BATCH.

7219
05:05:49,620 --> 05:05:51,355
INDUSTRY WANTS TO UNDERSTAND A

7220
05:05:51,355 --> 05:05:53,790
FAILED BACK AT DAY 2, 3 4-RBGS,

7221
05:05:53,790 --> 05:05:54,892
SO THEY CAN RESTART.

7222
05:05:54,892 --> 05:05:57,227
A FAILED BACK IN

7223
05:05:57,227 --> 05:05:57,928
BIOMANUFACTURING OF CELL

7224
05:05:57,928 --> 05:06:00,797
THERAPIES EQUALS A DEAD PATIENT.

7225
05:06:00,797 --> 05:06:03,133
AND THAT IS A HUGE BURDEN FOR US

7226
05:06:03,133 --> 05:06:05,369
TO THINK OF WHEN WE ARE THINKING

7227
05:06:05,369 --> 05:06:07,905
ABOUT CAR T OR SIMILAR

7228
05:06:07,905 --> 05:06:09,439
MANUFACTURING PROCESSES.

7229
05:06:09,439 --> 05:06:11,408
NEXT SLIDE PLEASE.

7230
05:06:11,408 --> 05:06:16,346
SO, THIS IS A PAPER IN 

7231
05:06:16,346 --> 05:06:17,881
PREDICTING T CELL QUALITY BASED

7232
05:06:17,881 --> 05:06:19,082
ON MULTI-OMICS, AND YOU CAN

7233
05:06:19,082 --> 05:06:20,851
CLICK ON THE NEXT SLIDE.

7234
05:06:20,851 --> 05:06:24,755
AND WE HAVE DONE THAT IN OTHER

7235
05:06:24,755 --> 05:06:26,823
PLATFORMS LIKE MSCs AND SO ON.

7236
05:06:26,823 --> 05:06:37,367
SO, THIS IS A PLATFORM TOOL OR A

7237
05:06:38,635 --> 05:06:42,339
WORK FLOW UNDERSTANDING EARLY

7238
05:06:42,339 --> 05:06:44,608
BATCH FAILURE OR TRAJECTORY, ONE

7239
05:06:44,608 --> 05:06:46,276
NEEDS TO BUILD IN MEASUREMENT

7240
05:06:46,276 --> 05:06:47,244
AND SENSORS IN MANUFACTURING TO

7241
05:06:47,244 --> 05:06:49,746
DO THAT AND CORRELATE THAT WITH

7242
05:06:49,746 --> 05:06:51,715
PRODUCT QUALITY.

7243
05:06:51,715 --> 05:06:52,115
NEXT SLIDE PLEASE.

7244
05:06:52,115 --> 05:06:55,352
AND THEN THE OTHER SIDE OF

7245
05:06:55,352 --> 05:06:57,220
THINGS -- SORRY, GO ANOTHER

7246
05:06:57,220 --> 05:06:57,654
SLIDE.

7247
05:06:57,654 --> 05:06:58,822
THANK YOU.

7248
05:06:58,822 --> 05:07:00,891
THE OTHER SIDE IS THAT

7249
05:07:00,891 --> 05:07:07,297
CORRELATION BETWEEN PRODUCT 

7250
05:07:07,297 --> 05:07:09,266
QUALITY AND PATIENT OUTCOME, WE

7251
05:07:09,266 --> 05:07:11,134
STARTED THIS ACROSS FIVE

7252
05:07:11,134 --> 05:07:12,569
CLINICAL CENTERS USING THREE

7253
05:07:12,569 --> 05:07:16,707
PRODUCTS THAT ARE COMMONLY USED

7254
05:07:16,707 --> 05:07:23,146
IN THE STEM CELL QUOTE/UNQUOTE

7255
05:07:23,146 --> 05:07:27,551
MARKET, ADIPOSE BONE MARROW AS 

7256
05:07:27,551 --> 05:07:36,059
ASPIRATE, EVERYONE SENT CELLS TO

7257
05:07:36,059 --> 05:07:38,362
GEORGIA TECH, SINGLE CELL, WE

7258
05:07:38,362 --> 05:07:41,598
CORRELATE THAT WITH THE CLINICAL

7259
05:07:41,598 --> 05:07:44,401
OUTCOME FOR EACH PATIENT.

7260
05:07:44,401 --> 05:07:48,772
THE BASE CLINICAL TRIAL RESULT

7261
05:07:48,772 --> 05:07:51,742
WAS PUBLISHED THIS WEEK IN

7262
05:07:51,742 --> 05:07:54,011
NATURE MEDICINE, OF THE

7263
05:07:54,011 --> 05:07:55,245
480-PATIENT TRIAL WE'RE WORKING

7264
05:07:55,245 --> 05:08:01,151
ON CORRELATES WITH THE

7265
05:08:01,151 --> 05:08:01,785
MULTI-OMICS MEASUREMENT,

7266
05:08:01,785 --> 05:08:05,455
INDIVIDUAL SPECIFIC PATIENT

7267
05:08:05,455 --> 05:08:06,757
OUTCOME.

7268
05:08:06,757 --> 05:08:10,260
A SHOUT OUT TO THE AMAZING

7269
05:08:10,260 --> 05:08:13,196
THINKING OF NIH TO ESTABLISH THE

7270
05:08:13,196 --> 05:08:17,034
HUB, WE SERVE AS IDCC AT GEORGIA

7271
05:08:17,034 --> 05:08:18,135
TECH, I JUST STEPPED DOWN FROM

7272
05:08:18,135 --> 05:08:21,672
THE P.I. OF THAT AS I MOVED TO

7273
05:08:21,672 --> 05:08:25,709
VANDERBILT, BUT THIS IS BRINGS

7274
05:08:25,709 --> 05:08:28,512
IN MANY OF THE PROGRAMS,

7275
05:08:28,512 --> 05:08:29,946
CLINICAL TRIALS AND PRE-CLINICAL

7276
05:08:29,946 --> 05:08:32,282
WORK AFTER CELLS GET SHIPPED TO

7277
05:08:32,282 --> 05:08:34,451
GEORGIA TECH FOR THIS DEEP

7278
05:08:34,451 --> 05:08:37,054
MULTIOMIC ANALYSIS.

7279
05:08:37,054 --> 05:08:39,589
AND I WOULD REALLY IMPLORE TO

7280
05:08:39,589 --> 05:08:41,892
MAKE SURE THESE TYPE OF DEEM

7281
05:08:41,892 --> 05:08:43,660
CHARACTERIZATION OF CELL THERAPY

7282
05:08:43,660 --> 05:08:44,628
PRODUCTS CONTINUE TO HAPPEN

7283
05:08:44,628 --> 05:08:52,602
ACROSS THE NIH, WHERE THERE'S A

7284
05:08:52,602 --> 05:08:55,105
CENTRALIZED PROGRAM, WHETHER N

7285
05:08:55,105 --> 05:08:57,674
NIH OR BGTC, A FUND OF FUND

7286
05:08:57,674 --> 05:08:59,943
MEMORIAL AS SECRETARY TO

7287
05:08:59,943 --> 05:09:00,811
UNDERSTANDING FOR REGULATORY

7288
05:09:00,811 --> 05:09:01,344
APPROVAL.

7289
05:09:01,344 --> 05:09:02,979
NEXT SLIDE PLEASE.

7290
05:09:02,979 --> 05:09:04,781
SO, THE BIGGEST ELEPHANT IN THE

7291
05:09:04,781 --> 05:09:07,517
ROOM IF YOU ASK OUR INDUSTRY

7292
05:09:07,517 --> 05:09:09,820
PARTNERS IS THAT OF QUALITY.

7293
05:09:09,820 --> 05:09:12,089
AND THAT REALLY MEANS WHAT ARE

7294
05:09:12,089 --> 05:09:15,492
MY CRITICAL QUALITY ATTRIBUTES

7295
05:09:15,492 --> 05:09:19,262
OF SUCH A COMPLEX DYNAMIC

7296
05:09:19,262 --> 05:09:20,464
PRODUCT THAT CHANGES AFTER

7297
05:09:20,464 --> 05:09:21,665
INJECTION INTO THE PATIENT, AND

7298
05:09:21,665 --> 05:09:24,401
THEN WHAT ARE THE RELATED

7299
05:09:24,401 --> 05:09:26,002
PROCESS PARAMETERS.

7300
05:09:26,002 --> 05:09:29,439
AND REALLY ANOTHER ISSUE AND

7301
05:09:29,439 --> 05:09:32,743
THOSE OF YOU WHO WERE AT THE

7302
05:09:32,743 --> 05:09:33,543
REGENERATIVE MEDICINE NATIONAL

7303
05:09:33,543 --> 05:09:35,545
ACADEMIES MEETING A FEW WEEKS

7304
05:09:35,545 --> 05:09:38,014
AGO, YOU KNOW, ALMOST EVERY

7305
05:09:38,014 --> 05:09:39,249
COMPANY SAID POTENCY, POTENCY,

7306
05:09:39,249 --> 05:09:39,616
POTENCY.

7307
05:09:39,616 --> 05:09:42,953
WE DON'T KNOW WHAT POTENCY

7308
05:09:42,953 --> 05:09:43,954
MEANS.

7309
05:09:43,954 --> 05:09:46,790
I REMEMBER A CONVERSATION WITH

7310
05:09:46,790 --> 05:09:53,463
FOLKS FROM U PENN WHO DID THE

7311
05:09:53,463 --> 05:10:00,570
ORIGINAL TRIALS IN PEDIATRIC ALL

7312
05:10:00,570 --> 05:10:06,910
AND ASKED POTENCY ASSAY FOR CAR

7313
05:10:06,910 --> 05:10:07,244
T.

7314
05:10:07,244 --> 05:10:08,979
WE'RE STILL THINKING ABOUT IT.

7315
05:10:08,979 --> 05:10:10,013
STEVE SAID MINE IS INJECTING

7316
05:10:10,013 --> 05:10:10,714
INTO THE KID.

7317
05:10:10,714 --> 05:10:12,282
I HAVE KNOWN OTHER THAT

7318
05:10:12,282 --> 05:10:12,983
PREDICTING ANYTHING WHAT WILL

7319
05:10:12,983 --> 05:10:15,585
HAPPEN IN THE PATIENT.

7320
05:10:15,585 --> 05:10:18,321
THIS IS FOR CAR T.

7321
05:10:18,321 --> 05:10:19,623
AND WHICH WE HAVE SO MUCH

7322
05:10:19,623 --> 05:10:22,025
EXPERIENCE ON.

7323
05:10:22,025 --> 05:10:23,426
SO UNDERSTANDING BETTER POTENCY

7324
05:10:23,426 --> 05:10:25,095
ASSAYS, NOW, WE NEED TO THINK

7325
05:10:25,095 --> 05:10:27,430
THIS IS DIFFERENT FROM RELEASE

7326
05:10:27,430 --> 05:10:27,731
ASSAYS.

7327
05:10:27,731 --> 05:10:28,765
RELEASE ASSAYS ARE DIFFERENT

7328
05:10:28,765 --> 05:10:30,700
THINGS WE STILL NEED TO DO

7329
05:10:30,700 --> 05:10:32,569
BETTER, CUT SHORT THE DURATION

7330
05:10:32,569 --> 05:10:36,072
OF THOSE ANALYSIS AND ASSAYS,

7331
05:10:36,072 --> 05:10:38,475
BUT PREDICTING POTENCY IS STILL

7332
05:10:38,475 --> 05:10:42,112
A HUGE GAP IN CELL THERAPY AND

7333
05:10:42,112 --> 05:10:46,383
AS A RESULT ALMOST MOST OF THE

7334
05:10:46,383 --> 05:10:47,484
CASES IN CELL-BASED THERAPY WE

7335
05:10:47,484 --> 05:10:49,586
DON'T KNOW THE MECHANISMS OF

7336
05:10:49,586 --> 05:10:51,855
ACTIONS VERY WELL, IN TERMS OF

7337
05:10:51,855 --> 05:10:55,592
THE NUANCES, ONE CAN SAY, YES,

7338
05:10:55,592 --> 05:10:58,628
CAR T CELL KILLS A TUMOR CELL,

7339
05:10:58,628 --> 05:11:01,264
FANTASTIC, BUT WHICH T CELLS,

7340
05:11:01,264 --> 05:11:02,599
WHAT FLAVOR OF T CELLS, WHAT

7341
05:11:02,599 --> 05:11:07,070
MAKES A DURABLE RESPONSE, WHY A

7342
05:11:07,070 --> 05:11:10,340
DURABLE RESPONSE IN MULTIPLE

7343
05:11:10,340 --> 05:11:12,309
MYELOMA PATIENT, WHY ONE PRODUCT

7344
05:11:12,309 --> 05:11:13,743
HAS LONGER DURABLE RESPONSE THAN

7345
05:11:13,743 --> 05:11:16,246
THAT OF ANOTHER COMPANY, BOTH

7346
05:11:16,246 --> 05:11:22,185
ARE CAR T, STILL AN ENIGMA AND

7347
05:11:22,185 --> 05:11:24,487
WE CAN'T DESIGN LARGE THERAPIES

7348
05:11:24,487 --> 05:11:25,155
WITHOUT UNDERSTANDING

7349
05:11:25,155 --> 05:11:25,622
FUNDAMENTAL BIOLOGIES.

7350
05:11:25,622 --> 05:11:26,456
NEXT SLIDE PLEASE.

7351
05:11:26,456 --> 05:11:28,825
AND IN MANY OF THESE CASES WHAT

7352
05:11:28,825 --> 05:11:32,729
WE HAVE BEEN DOING IN THE NSF

7353
05:11:32,729 --> 05:11:34,297
CENTER ARE BUILDING AN AREA OF

7354
05:11:34,297 --> 05:11:36,633
SENSORS THAT CAN BE INTEGRATED

7355
05:11:36,633 --> 05:11:38,034
IN THE MANUFACTURING PLATFORM.

7356
05:11:38,034 --> 05:11:39,903
I'LL GIVE YOU A FEW EXAMPLES.

7357
05:11:39,903 --> 05:11:42,839
I WILL NOT GO INTO DETAILS

7358
05:11:42,839 --> 05:11:45,175
BECAUSE OF TIME BUT REALLY

7359
05:11:45,175 --> 05:11:46,243
INTEGRATED WIRELESS SENSORS THAT

7360
05:11:46,243 --> 05:11:50,080
CAN GO INTO THE WALLS OF THE

7361
05:11:50,080 --> 05:11:52,182
BIOREACTORS AND IN REAL TIME

7362
05:11:52,182 --> 05:11:54,951
MEASURE PARAMETERS AND FEEDBACK

7363
05:11:54,951 --> 05:11:58,588
PARAMETERS, A LOT OF EFFORT IN

7364
05:11:58,588 --> 05:11:59,890
RAPID MICROBUILD DETECTION, NIST

7365
05:11:59,890 --> 05:12:03,960
HAS A CONSORTIUM ON THAT, THAT

7366
05:12:03,960 --> 05:12:08,164
WE'RE PART OF.

7367
05:12:08,164 --> 05:12:09,566
NON-DESTRICTIVE SENSORS FOR

7368
05:12:09,566 --> 05:12:11,101
MORPHOLOGY, CELL COUNTING, WE'RE

7369
05:12:11,101 --> 05:12:12,769
AT PRIMITIVE STAGES OF CELL

7370
05:12:12,769 --> 05:12:13,336
COUNTING.

7371
05:12:13,336 --> 05:12:15,205
THERE ARE FOUR, FIVE, SIX I

7372
05:12:15,205 --> 05:12:16,740
GUESS INSTRUMENTS FOR AUTOMATED

7373
05:12:16,740 --> 05:12:17,908
CELL COUNTING IN THE MARKET.

7374
05:12:17,908 --> 05:12:19,609
I CAN GUARANTEE YOU THEY ALL

7375
05:12:19,609 --> 05:12:22,145
COME IN WITH DIFFERENT ANSWERS

7376
05:12:22,145 --> 05:12:23,880
FOR A SINGLE VIAL OF CELLS.

7377
05:12:23,880 --> 05:12:27,384
THAT'S THE REALITY OF THE 

7378
05:12:27,384 --> 05:12:30,887
TECHNOLOGY RIGHT NOW.

7379
05:12:30,887 --> 05:12:31,321
METABOLIC IMAGING,

7380
05:12:31,321 --> 05:12:32,088
NON-DESTRUCTIVE, SO MANY.

7381
05:12:32,088 --> 05:12:34,958
YOU CAN CLICK THROUGH THE NEXT

7382
05:12:34,958 --> 05:12:38,161
THREE OR FOUR SLIDES PRETTY

7383
05:12:38,161 --> 05:12:38,395
QUICKLY.

7384
05:12:38,395 --> 05:12:40,063
SO, YEAH, THE OTHER THING I WANT

7385
05:12:40,063 --> 05:12:42,866
TO MENTION, TAKE A LITTLE BIT OF

7386
05:12:42,866 --> 05:12:45,802
TIME HERE FOR A MINUTE, AND

7387
05:12:45,802 --> 05:12:49,406
THINK ABOUT POTENCY ASSAYS.

7388
05:12:49,406 --> 05:12:51,841
WE BELIEVE THAT THE ORGANOID

7389
05:12:51,841 --> 05:12:54,477
FIELD AND TISSUE CHIP FIELD HAS

7390
05:12:54,477 --> 05:12:57,414
A LOT OF POTENTIAL IN DEVELOPING

7391
05:12:57,414 --> 05:12:59,616
BETTER POTENCY ASSAYS, IF WE CAN

7392
05:12:59,616 --> 05:13:01,918
TAKE CARE OF MANUFACTURING OF

7393
05:13:01,918 --> 05:13:02,852
REPRODUCIBLE MANUFACTURING OF

7394
05:13:02,852 --> 05:13:03,954
ORGANOIDS AND TISSUE CHIPS.

7395
05:13:03,954 --> 05:13:10,760
SO THIS IS A VERY, VERY GOOD

7396
05:13:10,760 --> 05:13:11,261
COLLABORATION, POTENTIAL

7397
05:13:11,261 --> 05:13:12,629
COLLABORATION WITH NCATS THAT

7398
05:13:12,629 --> 05:13:18,101
CAN HAPPEN IN CREATING DISEASE 

7399
05:13:18,101 --> 05:13:20,136
MODELS, WHERE CELL THERAPY CAN

7400
05:13:20,136 --> 05:13:23,039
TESTING YOU.

7401
05:13:23,039 --> 05:13:26,876
THIS IS MODEL OF BONE MARROW 

7402
05:13:26,876 --> 05:13:29,546
WITH A BONE LAYER, VAST CAR ON

7403
05:13:29,546 --> 05:13:30,013
TOP.

7404
05:13:30,013 --> 05:13:34,317
THE NEXT COUPLE SLIDES, WE HAVE

7405
05:13:34,317 --> 05:13:37,153
BEEN WORKING ON CREATING PATIENT

7406
05:13:37,153 --> 05:13:38,888
SPECIFIC MULTIPLE MYELOMA MODELS

7407
05:13:38,888 --> 05:13:43,059
WHERE THE MULTIPLE MYELOMA CELLS

7408
05:13:43,059 --> 05:13:45,562
ARE PRIMARILY PERIVASCULAR.

7409
05:13:45,562 --> 05:13:48,064
AND THEN WE HAVE BEEN FLOWING

7410
05:13:48,064 --> 05:13:50,100
CAR T CELLS THROUGH THE

7411
05:13:50,100 --> 05:13:53,837
VASCULATURE TO LOOK AT THE BONE

7412
05:13:53,837 --> 05:13:54,971
MARROW MULTIPLE MYELOMA

7413
05:13:54,971 --> 05:13:55,972
MICROENVIRONMENT.

7414
05:13:55,972 --> 05:13:57,841
THERE ARE COMPANIES NOW, LARGE

7415
05:13:57,841 --> 05:14:08,385
PHARMA COMPANIES, MOVING IN THIS

7416
05:14:21,331 --> 05:14:22,766
DIRECTION, AN AREA I HOPE THE

7417
05:14:22,766 --> 05:14:23,867
NIH INVESTS ON.

7418
05:14:23,867 --> 05:14:27,504
THE LAST SLIDE OR SO I WILL TALK

7419
05:14:27,504 --> 05:14:30,874
ABOUT IS THIS IDEA OF IN-PROCESS

7420
05:14:30,874 --> 05:14:32,609
MEASUREMENT AND MODULATION.

7421
05:14:32,609 --> 05:14:36,579
THE IDEA HERE IS TO REALLY SHIFT

7422
05:14:36,579 --> 05:14:37,881
THAT GAUSSIAN DISTRIBUTION OF

7423
05:14:37,881 --> 05:14:40,350
PATIENT OUTCOMES FROM RESPONDER

7424
05:14:40,350 --> 05:14:42,685
TO NON-RESPONDER AND PUSH THAT

7425
05:14:42,685 --> 05:14:46,489
TO A MORE RESPONDER SIDE BY

7426
05:14:46,489 --> 05:14:49,259
CREATING A UNIFORM PRODUCT

7427
05:14:49,259 --> 05:14:53,096
QUALITY THAT IS REFLECTIVE OF

7428
05:14:53,096 --> 05:14:56,399
THE PATIENT'S OUTCOME.

7429
05:14:56,399 --> 05:14:58,635
THIS REQUIRES UNDERSTANDING

7430
05:14:58,635 --> 05:15:00,036
CQAs, UNDERSTANDING PROCESS

7431
05:15:00,036 --> 05:15:00,870
PARAMETERS, REQUIRES

7432
05:15:00,870 --> 05:15:01,504
UNDERSTANDING AND DEVELOPING

7433
05:15:01,504 --> 05:15:05,341
TOOLS FOR CONTINUOUS OR REALTIME

7434
05:15:05,341 --> 05:15:06,209
MEASUREMENTS, AND UNDERSTANDING

7435
05:15:06,209 --> 05:15:08,078
ABOUT PROCESS VERY WELL TO BE

7436
05:15:08,078 --> 05:15:10,180
ABLE TO CONTROL THE PROCESS TO

7437
05:15:10,180 --> 05:15:11,448
GET A FIXED QUALITY PRODUCT.

7438
05:15:11,448 --> 05:15:13,450
NEXT SLIDE PLEASE.

7439
05:15:13,450 --> 05:15:17,454
AND I WILL END AT THIS SLIDE SO

7440
05:15:17,454 --> 05:15:20,423
THIS IS, YOU KNOW -- YOU CAN

7441
05:15:20,423 --> 05:15:25,829
CLICK THROUGH THIS.

7442
05:15:25,829 --> 05:15:28,665
REALLY A BIOREACTOR SYSTEM,

7443
05:15:28,665 --> 05:15:31,701
MANUSCRIPT UNDER REVIEW, WE TIKE

7444
05:15:31,701 --> 05:15:35,638
A FIBER CELL REACTOR, BUILT IN

7445
05:15:35,638 --> 05:15:40,043
SENSORS, CREATED A DIGITAL TWIN

7446
05:15:40,043 --> 05:15:41,778
MODEL FULLY COMPUTATIONALLY

7447
05:15:41,778 --> 05:15:43,746
BASED ON STANDARD BIOREACTOR

7448
05:15:43,746 --> 05:15:48,351
EQUATIONS, AND THEN WE HAVE A

7449
05:15:48,351 --> 05:15:50,820
GLUCOSE AND LACTIC MEASUREMENTS,

7450
05:15:50,820 --> 05:15:54,290
OPTICAL MEASUREMENTS  BUILT IN

7451
05:15:54,290 --> 05:15:59,062
TO ROBLE AT -- CONTROL AT A FIX

7452
05:15:59,062 --> 05:16:02,132
THE LEVEL RATHER THAN SPIKING IT

7453
05:16:02,132 --> 05:16:03,166
EVERY FEW DAYS, DATA AVAILABLE

7454
05:16:03,166 --> 05:16:07,470
IN THE CAR T SPACE AND MSC SPACE

7455
05:16:07,470 --> 05:16:09,506
LOOKING INTO EFFECT MUCH

7456
05:16:09,506 --> 05:16:10,173
CONTINUOUSLY CONTROLLED FEEDBACK

7457
05:16:10,173 --> 05:16:12,142
CONTROL BIOREACTOR.

7458
05:16:12,142 --> 05:16:16,246
I THINK THIS TO ME IS A PLATFORM

7459
05:16:16,246 --> 05:16:19,916
AGNOSTIC TYPE OF INVESTMENT THAT

7460
05:16:19,916 --> 05:16:21,417
IS WORTH HAPPENING AND WE'RE NOT

7461
05:16:21,417 --> 05:16:23,019
THE ONLY ONE.

7462
05:16:23,019 --> 05:16:27,423
FOLKS OUT OF CATAPULT AND UCL

7463
05:16:27,423 --> 05:16:28,525
ARE DOING THIS VERY WELL.

7464
05:16:28,525 --> 05:16:30,393
A LOT OF RECENT DEVELOPMENT IN

7465
05:16:30,393 --> 05:16:34,430
INDUSTRY IN TERMS OF CLOSED LOOP

7466
05:16:34,430 --> 05:16:35,532
MANUFACTURING SYSTEM STILL DON'T

7467
05:16:35,532 --> 05:16:36,366
HAVE ENOUGH SENSORS DEVELOPED

7468
05:16:36,366 --> 05:16:40,103
AROUND THAT AND WE THINK THAT IS

7469
05:16:40,103 --> 05:16:40,537
ABSOLUTELY NEEDED.

7470
05:16:40,537 --> 05:16:43,039
I WANT TO STOP TO GIVE FIVE

7471
05:16:43,039 --> 05:16:44,707
MINUTES FOR QUESTIONS, IF WE CAN

7472
05:16:44,707 --> 05:16:47,443
JUST GO AND CLICK THROUGH THE 

7473
05:16:47,443 --> 05:16:54,651
LAST SLIDE, THAT'S FINE.

7474
05:16:54,651 --> 05:16:56,119
I HAD SEVERAL SENSOR EXAMPLES

7475
05:16:56,119 --> 05:16:58,154
BUT WE DON'T NEED TO GO THROUGH

7476
05:16:58,154 --> 05:16:58,354
THAT.

7477
05:16:58,354 --> 05:17:00,056
I'LL END HERE, AND HAPPY TO

7478
05:17:00,056 --> 05:17:01,524
ANSWER QUESTIONS OR LEAVE THEM

7479
05:17:01,524 --> 05:17:08,331
FOR THE DISCUSSION AT THE END. 

7480
05:17:08,331 --> 05:17:11,067
>> DO WE WANT TO HOLD
QUESTIONS

7481
05:17:11,067 --> 05:17:12,936
UNTIL THE END OF THE THREE

7482
05:17:12,936 --> 05:17:17,173
SPEAKERS OR DO WE WANT TO --

7483
05:17:17,173 --> 05:17:23,046
>> [OFF MICROPHONE].

7484
05:17:23,046 --> 05:17:29,552
>> OKAY, DO WE HAVE ANY 

7485
05:17:29,552 --> 05:17:33,923
QUESTIONS FOR KRISH? 

7486
05:17:33,923 --> 05:17:35,592
>> THANK YOU SO MUCH.

7487
05:17:35,592 --> 05:17:37,327
IT WAS A GREAT PRESENTATION.

7488
05:17:37,327 --> 05:17:41,931
I'M WONDERING IF YOU WOULD

7489
05:17:41,931 --> 05:17:43,566
ELABORATE ON YOUR DIFFERENT

7490
05:17:43,566 --> 05:17:45,635
DEFINITION FOR RESPONDERS AND

7491
05:17:45,635 --> 05:17:46,936
NON-RESPONDERS AND HOW TO LOOK

7492
05:17:46,936 --> 05:17:48,838
AT THAT ISSUE DIFFERENTLY IN THE

7493
05:17:48,838 --> 05:17:51,341
CONTEXT OF THIS TYPE OF

7494
05:17:51,341 --> 05:17:51,841
THERAPIES?

7495
05:17:51,841 --> 05:17:57,914
I'M NOT SURE I FOLLOWED WHAT YOU

7496
05:17:57,914 --> 05:17:59,782
WERE --

7497
05:17:59,782 --> 05:18:02,085
>> SO THE PROCESS, THERE
ARE

7498
05:18:02,085 --> 05:18:04,120
MANY DIFFERENT KNOBS WE CAN

7499
05:18:04,120 --> 05:18:04,687
CONTROL.

7500
05:18:04,687 --> 05:18:08,524
OBVIOUSLY THERE'S HUGE PATIENT

7501
05:18:08,524 --> 05:18:09,025
VARIABILITY.

7502
05:18:09,025 --> 05:18:11,361
STARTING MATERIAL VARIABILITY.

7503
05:18:11,361 --> 05:18:13,563
DEPENDING WHETHER IT'S

7504
05:18:13,563 --> 05:18:14,998
AUTOLOGOUS OR ALLOGENEIC, MORE

7505
05:18:14,998 --> 05:18:15,865
VARIABILITY IN AUTOLOGOUS.

7506
05:18:15,865 --> 05:18:19,269
ONE OF THE THINGS WE SEE IS

7507
05:18:19,269 --> 05:18:21,237
VARIANCE IN OUR PRODUCT QUALITY,

7508
05:18:21,237 --> 05:18:22,071
RIGHT?

7509
05:18:22,071 --> 05:18:24,307
SO IF YOU TAKE CAR T, EVERYBODY

7510
05:18:24,307 --> 05:18:28,278
BATCH OF CAR T WE PRODUCE HAS

7511
05:18:28,278 --> 05:18:31,514
VERY DIFFERENT AMOUNTS OF MEMORY

7512
05:18:31,514 --> 05:18:33,583
T CELLS, CD8, CD4 T CELLS, ALL

7513
05:18:33,583 --> 05:18:35,451
KINDS OF LEVELS OF T CELLS IN

7514
05:18:35,451 --> 05:18:36,452
THERE.

7515
05:18:36,452 --> 05:18:40,456
IF YOU THINK ABOUT

7516
05:18:40,456 --> 05:18:44,060
iPSC-DERIVED CARDIOMYOCYTES

7517
05:18:44,060 --> 05:18:45,728
YOU'LL SEE A HETEROGENEOUS

7518
05:18:45,728 --> 05:18:46,362
DISTRIBUTION.

7519
05:18:46,362 --> 05:18:48,698
EVERY TIME WE HE MEASURE WE HAVE

7520
05:18:48,698 --> 05:18:52,535
A HETEROGENEOUS DISTRIBUTION. 

7521
05:18:52,535 --> 05:18:54,804
VARIABILITY IN CLINICAL TRIAL

7522
05:18:54,804 --> 05:18:57,640
CAN COME FROM PATIENT OR PRODUCT

7523
05:18:57,640 --> 05:18:58,841
VARIABILITY, REALLY THROUGH

7524
05:18:58,841 --> 05:19:01,244
AUTOMATION PROCESS CAN WE CREATE

7525
05:19:01,244 --> 05:19:02,378
VERY UNIFORM REPRODUCIBLE

7526
05:19:02,378 --> 05:19:03,980
PRODUCT WITH A NARROW

7527
05:19:03,980 --> 05:19:07,183
VARIABILITY THAT CAN AT LEAST

7528
05:19:07,183 --> 05:19:09,252
TAKE CARE OF THAT VARIATION TO

7529
05:19:09,252 --> 05:19:11,487
GIVE A MUCH BETTER UNIFORM

7530
05:19:11,487 --> 05:19:13,189
RESPONSE IN THE PATIENT

7531
05:19:13,189 --> 05:19:13,623
POPULATION.

7532
05:19:13,623 --> 05:19:15,491
WE REALLY NEED TO LOOK AT

7533
05:19:15,491 --> 05:19:18,861
PATIENT VARIABILITY TO SEE WHAT 

7534
05:19:18,861 --> 05:19:21,664
SUBSTRATA OF PATIENT CAN BE

7535
05:19:21,664 --> 05:19:23,700
BETTER RESPONDERS AND REALLY

7536
05:19:23,700 --> 05:19:25,234
PERSONALIZE OUR THERAPY TOWARDS

7537
05:19:25,234 --> 05:19:29,472
THAT STRATA OF PATIENTS.

7538
05:19:29,472 --> 05:19:31,140
 

7539
05:19:31,140 --> 05:19:35,611
>> ANY OTHER QUESTIONS?

7540
05:19:35,611 --> 05:19:35,978
OKAY.

7541
05:19:35,978 --> 05:19:39,649
THANK YOU SO MUCH FOR YOUR TIME

7542
05:19:39,649 --> 05:19:39,849
TODAY.

7543
05:19:39,849 --> 05:19:41,651
 

7544
05:19:41,651 --> 05:19:44,253
THE SECOND SPEAKER DOESN'T NEED

7545
05:19:44,253 --> 05:19:47,557
AN INTRODUCTION REALLY.

7546
05:19:47,557 --> 05:19:49,959
PROFESSOR OF ORTHOPEDIC SURGERY

7547
05:19:49,959 --> 05:19:56,999
AT WashU, A LEADER IN THE

7548
05:19:56,999 --> 05:20:00,002
FIELD OF MUSCULOSKELETAL SYSTEM.

7549
05:20:00,002 --> 05:20:03,239
 

7550
05:20:03,239 --> 05:20:04,540
>> THANK YOU, JOHNNY.

7551
05:20:04,540 --> 05:20:09,011
THANK YOU, BOB, AND THE 

7552
05:20:09,011 --> 05:20:11,114
ORGANIZERS FOR THIS FABULOUS

7553
05:20:11,114 --> 05:20:11,748
CONFERENCE.

7554
05:20:11,748 --> 05:20:12,482
YOU'LL SEE RECURRING THEMES,

7555
05:20:12,482 --> 05:20:14,350
QUESTIONS THAT COME UP FOR ALL

7556
05:20:14,350 --> 05:20:14,617
OF US.

7557
05:20:14,617 --> 05:20:18,087
CAN WE GET THE SLIDES UP?

7558
05:20:18,087 --> 05:20:24,127
 

7559
05:20:24,127 --> 05:20:25,561
 

7560
05:20:25,561 --> 05:20:34,537
>> GIVE US ONE SECOND. 

7561
05:20:34,537 --> 05:20:44,580
 

7562
05:21:17,680 --> 05:21:18,448
THANK YOU.

7563
05:21:18,448 --> 05:21:21,484
I'M GOING TO TALK ABOUT SOME

7564
05:21:21,484 --> 05:21:26,656
TOPICS DR. GOREMAN PROS IT,

7565
05:21:26,656 --> 05:21:30,293
REDESIGN STEM CELLS, MAKING

7566
05:21:30,293 --> 05:21:32,094
CELLS THAT HAVE SYNTHETIC

7567
05:21:32,094 --> 05:21:33,296
CAPABILITY FOR APPLICATION IN

7568
05:21:33,296 --> 05:21:34,363
REGENERATIVE MEDICINE.

7569
05:21:34,363 --> 05:21:36,966
WHEN WE TALK ABOUT MINIMAL

7570
05:21:36,966 --> 05:21:39,702
MANIPULATION, THIS IS THE OTHER

7571
05:21:39,702 --> 05:21:41,237
EXTREME OF MAXIMUM MANIPULATION,

7572
05:21:41,237 --> 05:21:42,605
HOPEFULLY TO ADDRESS A LOT OF

7573
05:21:42,605 --> 05:21:44,974
THESE ISSUES THAT KEEP COMING UP

7574
05:21:44,974 --> 05:21:46,676
IN TERMS OF REPRODUCIBILITY,

7575
05:21:46,676 --> 05:21:48,578
EFFICACY, SO ON, BUT AT THE COST

7576
05:21:48,578 --> 05:21:52,081
OF PROBABLY MAKING MORE COMPLEX

7577
05:21:52,081 --> 05:21:53,282
REGULATORY PROCEDURES.

7578
05:21:53,282 --> 05:21:54,617
AND PROCESSING SYSTEMS.

7579
05:21:54,617 --> 05:21:58,454
SO, OUR WORK IS FOCUSING ON THE

7580
05:21:58,454 --> 05:22:04,060
CONCEPT OF CELL-BASED THERAPY,

7581
05:22:04,060 --> 05:22:05,695
WE'VE HEARD ABOUT VARIOUS

7582
05:22:05,695 --> 05:22:09,298
APPROACHES TRYING TO REPAIR

7583
05:22:09,298 --> 05:22:10,800
FOCAL DEFECTS, WE'RE ALSO

7584
05:22:10,800 --> 05:22:11,767
INTERESTED IN TREATING

7585
05:22:11,767 --> 05:22:13,336
INFLAMMATORY JOINT DISEASES SUCH

7586
05:22:13,336 --> 05:22:15,938
AS RHEUMATOID ARTHRITIS AND OF

7587
05:22:15,938 --> 05:22:17,673
COURSE THE MOST DIFFICULT,

7588
05:22:17,673 --> 05:22:20,309
OSTEOARTHRITIS, WE HAVE TO

7589
05:22:20,309 --> 05:22:26,883
REGENERATE TISSUE, ALSO COMBAT 

7590
05:22:26,883 --> 05:22:28,651
INFLAMMATION IN THE JOINT.

7591
05:22:28,651 --> 05:22:30,052
WE TALKED ABOUT UNPROVEN STEM

7592
05:22:30,052 --> 05:22:30,853
CELL THERAPIES.

7593
05:22:30,853 --> 05:22:35,091
I WOULD GO ON A LIMB AND SAY

7594
05:22:35,091 --> 05:22:37,527
THESE THINGS THAT ARE BEING

7595
05:22:37,527 --> 05:22:41,564
ADVERTISED AS STEM CELL 

7596
05:22:41,564 --> 05:22:42,999
THERAPIES ARE NEITHER STEM CELLS

7597
05:22:42,999 --> 05:22:43,799
NOR THERAPIES.

7598
05:22:43,799 --> 05:22:46,235
THE PREMISE, IT WAS A GREAT

7599
05:22:46,235 --> 05:22:47,970
IDEA, JUST NOT TRUE YOU COULD

7600
05:22:47,970 --> 05:22:49,171
INJECT CELLS IN THE BODY, THEY

7601
05:22:49,171 --> 05:22:50,840
WOULD HONE TO THE SITE OF

7602
05:22:50,840 --> 05:22:51,841
INJURY, AUTOMATICALLY DO

7603
05:22:51,841 --> 05:22:54,310
EVERYTHING THEY NEED TO DO, AND

7604
05:22:54,310 --> 05:22:57,914
YOU SEE THESE ADS LIKE STRIP

7605
05:22:57,914 --> 05:23:00,783
MALL OR IN-FLIGHT MAGAZINE, THEY

7606
05:23:00,783 --> 05:23:03,553
KNOW WHAT YOU NEED IT, GO THERE

7607
05:23:03,553 --> 05:23:04,854
AND BECOME IT, AND IT'S NOT

7608
05:23:04,854 --> 05:23:05,054
TRUE.

7609
05:23:05,054 --> 05:23:07,523
THEY ALSO DO ALL THESE OTHER

7610
05:23:07,523 --> 05:23:11,227
THINGS, WE WERE TALKING AT LUNCH

7611
05:23:11,227 --> 05:23:15,064
ABOUT ADVERSE EFFECTS, STEM 

7612
05:23:15,064 --> 05:23:17,300
CELLS CAN SHOW OVERGROWTH,

7613
05:23:17,300 --> 05:23:18,234
HYPERPLASIA, OSSIFICATION AND

7614
05:23:18,234 --> 05:23:22,238
MSCs ARE SUPPOSED TO FORM

7615
05:23:22,238 --> 05:23:32,682
CARTILAGE, BAD REPORTS OF

7616
05:23:34,917 --> 05:23:36,152
MUCUS-PRODUCING, ISSUES OF

7617
05:23:36,152 --> 05:23:39,121
VISION LOSS, INFECTION, WE

7618
05:23:39,121 --> 05:23:45,227
TALKED ABOUT THIS, VERY FEW

7619
05:23:45,227 --> 05:23:46,829
PROSPECTIVE RANDOMIZED CLINICAL

7620
05:23:46,829 --> 05:23:48,431
TRIALS, ONLY 40% ARE PUBLISHED.

7621
05:23:48,431 --> 05:23:52,201
SOME CLINICAL TRIALS ARE NOT

7622
05:23:52,201 --> 05:23:53,336
ACTUALLY HAPPENING, THEY ARE

7623
05:23:53,336 --> 05:23:54,270
JUST ADVERTISING FOR COMPANIES

7624
05:23:54,270 --> 05:24:00,176
TO USE IT TO GAIN INVESTORS OR

7625
05:24:00,176 --> 05:24:02,411
OTHER NOT-TRUE CLINICAL TRIALS.

7626
05:24:02,411 --> 05:24:05,448
SO YOU JUST HEARD FROM DR. ROY

7627
05:24:05,448 --> 05:24:06,582
ABOUT AN EXCELLENT CLINICAL

7628
05:24:06,582 --> 05:24:11,487
TRIAL THAT WAS PUBLISHED A FEW 

7629
05:24:11,487 --> 05:24:13,556
DAYS AGO IN NATURE MEDICINE,

7630
05:24:13,556 --> 05:24:17,093
KRISH WAS PART OF THIS, THEY

7631
05:24:17,093 --> 05:24:18,027
COMPARED THREE COMMON CELL-BASED

7632
05:24:18,027 --> 05:24:21,697
THERAPY INJECTIONS IN THE KNEE,

7633
05:24:21,697 --> 05:24:23,132
BONE MARROW, ASPIRATE

7634
05:24:23,132 --> 05:24:26,435
CONCENTRATION, ADIPOSE STEM 

7635
05:24:26,435 --> 05:24:28,004
CELLS, UMBILICAL CORD, YOU CAN

7636
05:24:28,004 --> 05:24:29,372
SEE THERE WAS NO EFFECT.

7637
05:24:29,372 --> 05:24:30,906
IN ANYTHING THERE WAS A PLACEBO

7638
05:24:30,906 --> 05:24:32,375
EFFECT WHICH IS SHOWN FOR

7639
05:24:32,375 --> 05:24:34,110
INJECTING ANYTHING INTO THE KNEE

7640
05:24:34,110 --> 05:24:39,815
OF ABOUT 30 OR 40%, WHICH IS

7641
05:24:39,815 --> 05:24:40,216
TYPICAL.

7642
05:24:40,216 --> 05:24:42,852
SO, THESE NAIVE CELL INJECTIONS

7643
05:24:42,852 --> 05:24:43,953
DON'T REALLY STICK AROUND.

7644
05:24:43,953 --> 05:24:46,889
THERE ARE ALL THESE ISSUES WITH

7645
05:24:46,889 --> 05:24:48,758
THESE NAIVE CELLS THAT WE'VE

7646
05:24:48,758 --> 05:24:50,292
TALKED ABOUT.

7647
05:24:50,292 --> 05:24:52,461
SORRY, THIS IS SLOW.

7648
05:24:52,461 --> 05:24:54,897
SO, CAN YOU BACK UP ONE?

7649
05:24:54,897 --> 05:24:58,067
ONE TOO FAR.

7650
05:24:58,067 --> 05:24:58,434
OKAY.

7651
05:24:58,434 --> 05:25:01,470
NOW ONE FORWARD.

7652
05:25:01,470 --> 05:25:03,973
SO, THE PROBLEM IS THAT THESE

7653
05:25:03,973 --> 05:25:05,041
CELLS ARE NOT UNIFORM.

7654
05:25:05,041 --> 05:25:07,443
WE'VE DONE A NUMBER OF

7655
05:25:07,443 --> 05:25:08,644
SINGLE-CELL STUDIES, YOU FIND

7656
05:25:08,644 --> 05:25:11,614
THE STANDARD PREP OF WHAT WE

7657
05:25:11,614 --> 05:25:13,683
CALL MSCs OR ASCs, NOT ONE

7658
05:25:13,683 --> 05:25:15,551
CELL TYPE AS DR. HUARD

7659
05:25:15,551 --> 05:25:18,054
MENTIONED, ONE IN 10,000 MIGHT

7660
05:25:18,054 --> 05:25:20,256
BE A TRUE MULTI-POTENT STEM CELL

7661
05:25:20,256 --> 05:25:23,426
BUT THIS IS A PLOT SHOWING AT

7662
05:25:23,426 --> 05:25:25,861
LEAST THREE TO FIVE TO SEVEN

7663
05:25:25,861 --> 05:25:29,331
CLUSTERS IN YOUR STANDARD MSC

7664
05:25:29,331 --> 05:25:32,868
PREP, WITH PASSAGE THEY CHANGE

7665
05:25:32,868 --> 05:25:33,936
FROM LABORATORY TO LABORATORY

7666
05:25:33,936 --> 05:25:35,204
THEY CHANGE, AND IF YOU INJECT

7667
05:25:35,204 --> 05:25:38,541
CELLS THEY ARE GONE IN A DAY OR

7668
05:25:38,541 --> 05:25:38,708
TWO.

7669
05:25:38,708 --> 05:25:40,409
MOSTLY APOPTOSE AND GET CLEARED,

7670
05:25:40,409 --> 05:25:42,178
DON'T HONE TO SITES.

7671
05:25:42,178 --> 05:25:45,114
AND THEY HAVE RELATIVELY LOW

7672
05:25:45,114 --> 05:25:49,351
THERAPEUTIC EFFECT. 

7673
05:25:49,351 --> 05:25:51,654
SO, THESE LOW EFFECTS AND

7674
05:25:51,654 --> 05:25:52,755
INTERDONOR VARIABILITY IS A

7675
05:25:52,755 --> 05:25:55,691
CONSIDERABLE ISSUE TO TRY TO

7676
05:25:55,691 --> 05:25:55,958
ADDRESS.

7677
05:25:55,958 --> 05:25:58,127
SO, OUR TARGETS AND MANY OF THE

7678
05:25:58,127 --> 05:26:00,563
TARGETS OF THEM CELL INJECTIONS

7679
05:26:00,563 --> 05:26:03,265
HAVE BEEN INFLAMMATORY

7680
05:26:03,265 --> 05:26:03,766
PROCESSES.

7681
05:26:03,766 --> 05:26:04,266
SO, OSTEOARTHRITIS IN

7682
05:26:04,266 --> 05:26:06,335
PARTICULAR, ON THE RIGHT, GOING

7683
05:26:06,335 --> 05:26:07,970
FROM NORMAL JOINT TO ARTHRITIC

7684
05:26:07,970 --> 05:26:09,538
JOINT IS A VERY INFLAMMATORY

7685
05:26:09,538 --> 05:26:09,805
DISEASE.

7686
05:26:09,805 --> 05:26:12,808
IT'S DRIVEN BY A NUMBER OF OTHER

7687
05:26:12,808 --> 05:26:13,476
FACTORS SUCH AS BIOMECHANICS,

7688
05:26:13,476 --> 05:26:16,312
GENETICS, SO ON, BUT HAS

7689
05:26:16,312 --> 05:26:17,046
INFLAMMATORY COMPONENT THAT

7690
05:26:17,046 --> 05:26:20,249
LEADS THROUGH SOME OF OUR

7691
05:26:20,249 --> 05:26:22,685
CLASSIC CYTOKINES, INTERLEUKIN

7692
05:26:22,685 --> 05:26:26,922
1, TNF ALPHA, UPREGULATION OF

7693
05:26:26,922 --> 05:26:28,057
METALLOPROTEASE AND OTHER

7694
05:26:28,057 --> 05:26:29,125
INFLAMMATORY MEDIATORS THAT

7695
05:26:29,125 --> 05:26:31,527
BREAK DOWN THE CARTILAGE, CAUSE

7696
05:26:31,527 --> 05:26:33,496
BONE REMODELING, AND PAIN, WHICH

7697
05:26:33,496 --> 05:26:34,530
IS THE ULTIMATE OUTCOME IF

7698
05:26:34,530 --> 05:26:36,031
YOU'RE JOINT LOOKED LIKE THE ONE

7699
05:26:36,031 --> 05:26:37,066
ON THE BOTTOM BUT DIDN'T HURT

7700
05:26:37,066 --> 05:26:38,901
YOU WOULDN'T GO TO THE DOCTOR

7701
05:26:38,901 --> 05:26:39,735
AND WOULDN'T HAVE ANYTHING DONE

7702
05:26:39,735 --> 05:26:40,402
FOR IT.

7703
05:26:40,402 --> 05:26:43,672
SO IT'S ALL REALLY ABOUT THE

7704
05:26:43,672 --> 05:26:45,875
PAIN WE'RE TRYING TO TREAT.

7705
05:26:45,875 --> 05:26:47,610
SO, INFLAMMATION OF COURSE IS AN

7706
05:26:47,610 --> 05:26:49,245
IMPORTANT AND NECESSARY PROCESS

7707
05:26:49,245 --> 05:26:51,113
BUT WE WANT RESOLVING

7708
05:26:51,113 --> 05:26:51,714
INFLAMMATION.

7709
05:26:51,714 --> 05:26:53,649
THE CONCEPT OF WOUND HEALING OR

7710
05:26:53,649 --> 05:26:56,619
RESPONSE TO VACCINE OR ANYTHING

7711
05:26:56,619 --> 05:26:58,921
IS INITIAL INFLAMMATORY PHASE,

7712
05:26:58,921 --> 05:27:03,292
FOLLOWED BY A POST INFLAMMATORY

7713
05:27:03,292 --> 05:27:04,059
RESOLUTION, INFLAMMATION GOES

7714
05:27:04,059 --> 05:27:08,364
AWAY, YOU HAVE THE SECONDARY

7715
05:27:08,364 --> 05:27:09,031
INFLUX OF INFLAMMATORY CELLS,

7716
05:27:09,031 --> 05:27:11,634
CLEAN UP THE AREA SUCH AS

7717
05:27:11,634 --> 05:27:13,102
MACROPHAGES AND DENDRITIC CELLS.

7718
05:27:13,102 --> 05:27:14,837
THE PROBLEM IS NOT INFLAMMATION.

7719
05:27:14,837 --> 05:27:16,772
IT'S CHRONIC INFLAMMATION, OR

7720
05:27:16,772 --> 05:27:17,973
UNCONTROLLED INFLAMMATION.

7721
05:27:17,973 --> 05:27:21,844
SO, IN DISEASES SUCH AS

7722
05:27:21,844 --> 05:27:22,511
AUTOIMMUNE DISEASE,

7723
05:27:22,511 --> 05:27:23,279
OSTEOARTHRITIS, OBESITY, CARDIAC

7724
05:27:23,279 --> 05:27:24,480
DISEASE, MANY OTHER ONES, YOU

7725
05:27:24,480 --> 05:27:28,884
HAVE CHRONIC FAST  --

7726
05:27:28,884 --> 05:27:32,221
INFLAMMATION DRIVEN BY THE SAME

7727
05:27:32,221 --> 05:27:32,521
CYTOKINES.

7728
05:27:32,521 --> 05:27:38,727
CHRONIC AND CYCLES SO YOU CAN

7729
05:27:38,727 --> 05:27:40,462
HAVE DIURNAL OR CIRCADIAN

7730
05:27:40,462 --> 05:27:41,764
VARIATION AND ENVIRONMENTALLY

7731
05:27:41,764 --> 05:27:45,367
TRIGGERED CHANGES IN

7732
05:27:45,367 --> 05:27:45,701
INFLAMMATION.

7733
05:27:45,701 --> 05:27:46,769
MOST THERAPIES ARE CONTINUOUS

7734
05:27:46,769 --> 05:27:47,169
PROTEIN.

7735
05:27:47,169 --> 05:27:54,577
IF HAVE YOU RHEUMATOID 

7736
05:27:54,577 --> 05:28:05,087
ARTHRITIS YOU GET HIGH DOSES.

7737
05:28:06,589 --> 05:28:09,892
AS I MENTIONED THEY ARE GIVEN

7738
05:28:09,892 --> 05:28:10,826
CONTINUOUSLY BUT DISEASE FLARES,

7739
05:28:10,826 --> 05:28:13,095
GOES UP AND DOWN.

7740
05:28:13,095 --> 05:28:14,363
SO WE'RE GENERALLY OVERDOSING

7741
05:28:14,363 --> 05:28:14,964
WITH DRUGS AND WE DON'T KNOW

7742
05:28:14,964 --> 05:28:19,802
WHICH ONE OF THE TARGETS TO HIT.

7743
05:28:19,802 --> 05:28:24,607
SO WE SOMEHOW NEED TO MOMENT 

7744
05:28:24,607 --> 05:28:33,716
MOMENT LEGS.

7745
05:28:33,716 --> 05:28:37,987
 

7746
05:28:37,987 --> 05:28:38,254
MULTIPLEX.

7747
05:28:38,254 --> 05:28:40,756
WE HAD A THOUGHT TEN YEARS AGO

7748
05:28:40,756 --> 05:28:43,225
WE COULD USE GENOME EDITING

7749
05:28:43,225 --> 05:28:44,827
METHODS TO REDESIGN THE SENSORY

7750
05:28:44,827 --> 05:28:47,196
APPARATUS ON A CELL, INTERNAL

7751
05:28:47,196 --> 05:28:49,632
GENE CIRCUITS, AND OUTPUT WHICH

7752
05:28:49,632 --> 05:28:53,402
COULD BE CYTOKINE INHIBITORS,

7753
05:28:53,402 --> 05:28:54,870
PAIN INHIBITORS, ANABOLIC

7754
05:28:54,870 --> 05:28:55,337
PROMOTERS.

7755
05:28:55,337 --> 05:28:57,806
AND LONG STORY SHORT WE STARTED

7756
05:28:57,806 --> 05:28:59,842
BEFORE CRISPR WAS MADE AVAILABLE

7757
05:28:59,842 --> 05:29:02,044
AND POPULAR BUT SWITCHED

7758
05:29:02,044 --> 05:29:03,045
IMMEDIATELY TO CRISPR-BASED

7759
05:29:03,045 --> 05:29:07,182
METHODS WHICH MADE  MADE IT

7760
05:29:07,182 --> 05:29:09,451
EASIER, ABLE TO FIGURE OUT THE

7761
05:29:09,451 --> 05:29:10,552
NETWORK THAT DRIVES INFLAMMATORY

7762
05:29:10,552 --> 05:29:13,188
RESPONSES IN STEM CELLS ALMOST

7763
05:29:13,188 --> 05:29:15,824
ALL OUR WORK IN iPSCs TO

7764
05:29:15,824 --> 05:29:16,792
CLONE, HAVE UNIFORM POPULATIONS,

7765
05:29:16,792 --> 05:29:18,761
WHICH THEY ARE NOT UNIFORM BY

7766
05:29:18,761 --> 05:29:20,562
THE WAY, MUCH MORE UNIFORM THAN

7767
05:29:20,562 --> 05:29:21,830
MSCs BUT WE TALKED ABOUT THAT

7768
05:29:21,830 --> 05:29:22,932
EARLIER TOO.

7769
05:29:22,932 --> 05:29:25,434
THAT A POOL OF iPSCs IS

7770
05:29:25,434 --> 05:29:26,535
QUITE NON-UNIFORM.

7771
05:29:26,535 --> 05:29:29,705
WE CAN GO INTO GENE CIRCUITS AND

7772
05:29:29,705 --> 05:29:31,774
DIVERT INFLAMMATORY RESPONSES TO

7773
05:29:31,774 --> 05:29:33,876
A THERAPEUTIC RESPONSE AND

7774
05:29:33,876 --> 05:29:34,944
CREATE BIOLOGIC FEEDBACK LOOPS

7775
05:29:34,944 --> 05:29:37,680
WHERE WE CAN TREAT DISEASE

7776
05:29:37,680 --> 05:29:40,015
AUTOMATICALLY WITH THESE CELLS.

7777
05:29:40,015 --> 05:29:42,184
SO, BASICALLY LIKE TO THINK OF

7778
05:29:42,184 --> 05:29:45,988
IT AS A CELL, AS AN iPHONE YOU

7779
05:29:45,988 --> 05:29:50,659
CAN PUT  SNIPPETS OF CODE IN,

7780
05:29:50,659 --> 05:29:55,097
APPS, THROUGH CRISPR OR VIRAL

7781
05:29:55,097 --> 05:29:55,564
METHODS.

7782
05:29:55,564 --> 05:29:58,567
THE FIRST ATTEMPT WAS BY A

7783
05:29:58,567 --> 05:30:01,136
Ph.D. STUDENT, FACULTY AT

7784
05:30:01,136 --> 05:30:03,772
VANDERBILT NOW, TARGETING TNF

7785
05:30:03,772 --> 05:30:07,676
AND IL-1 PATHWAYS, TRACK  DOWN

7786
05:30:07,676 --> 05:30:10,079
THE GENES ACTIVITED, CAME UP

7787
05:30:10,079 --> 05:30:12,481
WITH TARGET GENES DRIVERS OF

7788
05:30:12,481 --> 05:30:15,351
THIS RESPONSE, REALLY GOOD

7789
05:30:15,351 --> 05:30:16,552
SURROGATES FOR CYTOKINE LEVELS

7790
05:30:16,552 --> 05:30:17,853
OUTSIDE THE CELL.

7791
05:30:17,853 --> 05:30:20,189
I WON'T GO INTO TEE OF DETAILS

7792
05:30:20,189 --> 05:30:22,124
BUT THIS IS PUBLISHED.

7793
05:30:22,124 --> 05:30:24,293
CCL2 IN PARTICULAR WAS AN

7794
05:30:24,293 --> 05:30:25,728
EXCELLENT SURROGATE MEASURE FOR

7795
05:30:25,728 --> 05:30:28,664
CYTOKINE LEVELS OUTSIDE THE

7796
05:30:28,664 --> 05:30:30,666
CELL, THIS WAS IN YEAR AFTER

7797
05:30:30,666 --> 05:30:33,535
CRISPR WAS MADE AVAILABLE, I

7798
05:30:33,535 --> 05:30:38,140
WENT IN USING CRISPR/CAS9 IN OUR

7799
05:30:38,140 --> 05:30:44,847
LAB, BASICALLY  RE REPURPOSES TO

7800
05:30:44,847 --> 05:30:50,386
CREATE THE INHIBITOR OF TNF, SOL

7801
05:30:50,386 --> 05:30:57,092
I'M TNFR 1, MADE INTERLEUKIN 1 

7802
05:30:57,092 --> 05:30:58,360
RECEPTOR AGONIST AS INHIBITOR.

7803
05:30:58,360 --> 05:31:04,133
THE TRICK BEHIND THAT IS TO CUT

7804
05:31:04,133 --> 05:31:06,402
OPEN THE CCL2 PROMOTER, PUT IN

7805
05:31:06,402 --> 05:31:10,439
INHIBITOR OF TLF OR IL-1, NOW

7806
05:31:10,439 --> 05:31:13,575
WHEN THE CELL SEES CYTOKINES IT

7807
05:31:13,575 --> 05:31:15,544
MAKES PROPORTIONAL AMOUNT OF

7808
05:31:15,544 --> 05:31:18,047
DRUG TO BLOCK THE CYTOKINE.

7809
05:31:18,047 --> 05:31:20,182
AND THROUGH A FEW TESTS WE WERE

7810
05:31:20,182 --> 05:31:23,185
ABLE TO MAKE IT PROPORTIONAL AND

7811
05:31:23,185 --> 05:31:27,189
AMPLIFY WITH MULTIPLE COPIES OF 

7812
05:31:27,189 --> 05:31:32,094
THE GENE, WE CAN SUPPRESS AND

7813
05:31:32,094 --> 05:31:37,132
TUNE USING CRISPR CRAB, APPROACH

7814
05:31:37,132 --> 05:31:38,267
TO INHIBIT EXPRESSION OF

7815
05:31:38,267 --> 05:31:38,534
RECEPTOR.

7816
05:31:38,534 --> 05:31:40,536
WE SHOWED THIS WORKS WITH

7817
05:31:40,536 --> 05:31:44,673
INCREASING DOSE AND TIME OF TNF,

7818
05:31:44,673 --> 05:31:46,208
YOU MAKE MORE TNF INHIBITOR,

7819
05:31:46,208 --> 05:31:48,110
GENE EXPRESSION GOES UP AT FIRST

7820
05:31:48,110 --> 05:31:49,611
BUT SELF-REGULATES, YOU SEE ON

7821
05:31:49,611 --> 05:31:51,046
THE RIGHT SIDE GRAPH, AFTER A

7822
05:31:51,046 --> 05:31:52,414
FEW HOURS SHUTS OFF.

7823
05:31:52,414 --> 05:31:54,883
WE SHOWED IT COULD PROTECT THE

7824
05:31:54,883 --> 05:31:57,186
CARTILAGE FROM EITHER TNF OR

7825
05:31:57,186 --> 05:31:57,820
IL-1 INSULTS.

7826
05:31:57,820 --> 05:32:00,189
NEXT STEP WAS TO GO TO AN ANIMAL

7827
05:32:00,189 --> 05:32:02,925
MODEL, AND WE RAN INTO THE

7828
05:32:02,925 --> 05:32:05,194
PROBLEM OF CELL ENGRAFTMENT.

7829
05:32:05,194 --> 05:32:06,061
WE TRIED INJECTING CELLS.

7830
05:32:06,061 --> 05:32:07,463
IF I LISTENED TO THE FIRST HALF

7831
05:32:07,463 --> 05:32:09,098
I WOULD KNOW THEY WOULD NOT

7832
05:32:09,098 --> 05:32:10,866
ENGRAFT SO THEY DIDN'T AFTER TWO

7833
05:32:10,866 --> 05:32:12,534
DAYS ALL THE CELLS WERE GONE.

7834
05:32:12,534 --> 05:32:15,237
TO KEEP THEM IN PLACE, WE

7835
05:32:15,237 --> 05:32:17,306
ENGINEERED THEM INTO A SMALL

7836
05:32:17,306 --> 05:32:18,740
PIECE OF CARTILAGE.

7837
05:32:18,740 --> 05:32:21,376
THIS WAS ADVANTAGEOUS BECAUSE

7838
05:32:21,376 --> 05:32:23,112
CARTILAGE IS AVASCULAR, ANEURAL,

7839
05:32:23,112 --> 05:32:25,080
IT WILL SIT SUBCUTANEOUSLY OR IN

7840
05:32:25,080 --> 05:32:27,816
THE JOINT AND GET ALL NUTRIENTS

7841
05:32:27,816 --> 05:32:29,685
AND SIGNALS THROUGH DIFFUSION.

7842
05:32:29,685 --> 05:32:32,721
SO IT WILL SURVIVE WE SHOW OVER

7843
05:32:32,721 --> 05:32:34,323
SIX MONTHS WITHOUT ANY CELLS

7844
05:32:34,323 --> 05:32:36,391
CRAWLING OUT OR CELLS TURNING

7845
05:32:36,391 --> 05:32:38,093
OVER, AND WE IMPLANT THIS IN THE

7846
05:32:38,093 --> 05:32:43,665
BACK OF A MOUSE, SUCH AS A KBXN

7847
05:32:43,665 --> 05:32:46,301
MODEL OF RHEUMATOID ARTHRITIS

7848
05:32:46,301 --> 05:32:47,369
CAUSED BY INJECTION OF SERUM.

7849
05:32:47,369 --> 05:32:51,874
THIS IS DATA SHOWING INJECTION

7850
05:32:51,874 --> 05:32:53,742
OF CELLS, WITHIN THE CELLS --

7851
05:32:53,742 --> 05:32:55,144
CELLS RESPOND WITHIN 20 MINUTES

7852
05:32:55,144 --> 05:32:57,146
WITH THERAPEUTIC RESPONSE BUT

7853
05:32:57,146 --> 05:32:58,881
THEY ARE GONE WITHIN 24-48

7854
05:32:58,881 --> 05:32:59,515
HOURS.

7855
05:32:59,515 --> 05:33:01,450
IF WE USE IMPLANTS, THEY AGAIN

7856
05:33:01,450 --> 05:33:03,585
RESPOND WITHIN 20 MINUTES BUT

7857
05:33:03,585 --> 05:33:04,686
SIX MONTHS LATER THE IMPLANT IS

7858
05:33:04,686 --> 05:33:05,888
STILL THERE.

7859
05:33:05,888 --> 05:33:08,924
SO IT'S A NICE POTENTIAL FOR

7860
05:33:08,924 --> 05:33:10,192
VERY LONG-TERM SOLUTION.

7861
05:33:10,192 --> 05:33:13,028
SO, WHEN WE TEST IN THE HOUSE WE

7862
05:33:13,028 --> 05:33:14,329
LOOK AT PAIN SENSITIVITY, AND

7863
05:33:14,329 --> 05:33:17,299
WHAT WE FIND IS THAT OUR

7864
05:33:17,299 --> 05:33:18,534
TREATMENT GROUPS CAUSE A

7865
05:33:18,534 --> 05:33:23,205
SIGNIFICANT REDUCTION IN PAIN

7866
05:33:23,205 --> 05:33:28,110
SENSITIVITY CAUSED BY RHEUMATOID

7867
05:33:28,110 --> 05:33:28,977
ARTHRITIS, REDUCTION FROM

7868
05:33:28,977 --> 05:33:31,213
IMPLANTS, COMPLETE ELIMINATION

7869
05:33:31,213 --> 05:33:32,781
OF THE BONE EROSIONS CAUSED BY

7870
05:33:32,781 --> 05:33:34,516
RHEUMATOID ARTHRITIS.

7871
05:33:34,516 --> 05:33:37,886
THIS IS AN IL-1 R.A. DELIVERING

7872
05:33:37,886 --> 05:33:39,955
IMPLANT FOR THIS MODEL, VERY

7873
05:33:39,955 --> 05:33:44,226
IL-1 DEPENDENT.

7874
05:33:44,226 --> 05:33:45,961
NOW WE CAN MULTIPLEX.

7875
05:33:45,961 --> 05:33:47,262
HOW DO WE KEEP TRACK?

7876
05:33:47,262 --> 05:33:48,830
HOW DO WE SHUT THEM OFF IF WE

7877
05:33:48,830 --> 05:33:49,665
NEED TO?

7878
05:33:49,665 --> 05:33:54,203
WE CAN PUT IN THE OTHER APPS,

7879
05:33:54,203 --> 05:33:57,906
THESE ARE iPSCs, CAN BE

7880
05:33:57,906 --> 05:33:59,007
DIFFERENTIATED, OR VIRAL VECTORS

7881
05:33:59,007 --> 05:34:01,076
CAN GO INTO PRIMARY CELLS.

7882
05:34:01,076 --> 05:34:04,446
WE CAN BIND WITH LUCIFERASE OR

7883
05:34:04,446 --> 05:34:06,081
GFP, TIE TO THE THERAPEUTIC

7884
05:34:06,081 --> 05:34:09,284
MOLECULES TO GET A READOUT OF

7885
05:34:09,284 --> 05:34:12,454
INFLAMMATION AND SIGNAL.

7886
05:34:12,454 --> 05:34:13,956
WE CAN USE VARIOUS SMALL

7887
05:34:13,956 --> 05:34:15,891
MOLECULES TO TURN ON AND OFF

7888
05:34:15,891 --> 05:34:17,693
THOSE GENE CIRCUITS, IF YOU NEED

7889
05:34:17,693 --> 05:34:20,329
TO TEMPORARILY SHUT THEM OFF YOU

7890
05:34:20,329 --> 05:34:21,763
CAN.

7891
05:34:21,763 --> 05:34:24,032
WE IS A SYSTEM FOR SELF

7892
05:34:24,032 --> 05:34:28,437
DESTRUCT, WE KILL ALL THE CELLS.

7893
05:34:28,437 --> 05:34:31,039
WE GOT A TOUCH SENSOR,

7894
05:34:31,039 --> 05:34:32,474
MECHANICALLY SENSITIVE ENOUGH TO

7895
05:34:32,474 --> 05:34:34,009
MAKE DRUGS, AND I'LL TELL YOU

7896
05:34:34,009 --> 05:34:36,078
ABOUT THE TOUCH SENSOR AND CLOCK

7897
05:34:36,078 --> 05:34:39,181
APPS, WHY WE WANT THEM AND WHY

7898
05:34:39,181 --> 05:34:41,817
WE NEED THEM FOR DRUG DELIVERY.

7899
05:34:41,817 --> 05:34:48,490
THIS IS PUBLISHED A COUPLE YEARS

7900
05:34:48,490 --> 05:34:49,324
AGO.

7901
05:34:49,324 --> 05:34:51,093
MECHANOGENETICS, LIKE OPT

7902
05:34:51,093 --> 05:34:52,628
GENETICS, WE CAN TURN GENES ON

7903
05:34:52,628 --> 05:34:53,428
WITH MECHANICAL LOADING.

7904
05:34:53,428 --> 05:34:55,530
IF YOU HAVE CARTILAGE WHEN IT'S

7905
05:34:55,530 --> 05:34:57,299
LOADED YOU CAN MAKE A DRUG AND

7906
05:34:57,299 --> 05:34:58,767
BY LOOKING AT DIFFERENT LEVELS

7907
05:34:58,767 --> 05:35:00,736
OF LOADING YOU CAN GET DIFFERENT

7908
05:35:00,736 --> 05:35:03,805
DRUGS OR DIFFERENT AMOUNTS OF

7909
05:35:03,805 --> 05:35:04,306
DRUG.

7910
05:35:04,306 --> 05:35:11,880
WE HAVE TO IDENTIFY MECHANISMS,

7911
05:35:11,880 --> 05:35:15,584
THEY WERE ION CHANNELS,

7912
05:35:15,584 --> 05:35:16,585
DECONSTRUCT THE PATHWAY, FIND

7913
05:35:16,585 --> 05:35:18,854
THE HUB AND NODE GENES THAT

7914
05:35:18,854 --> 05:35:21,223
DRIVE THE RESPONSE TO MECHANICAL

7915
05:35:21,223 --> 05:35:22,824
LOADING, INSERT YOUR THERAPEUTIC

7916
05:35:22,824 --> 05:35:24,359
MOLECULE INTO THOSE DIFFERENT

7917
05:35:24,359 --> 05:35:27,963
HUBS, AND THEN SHOW THAT

7918
05:35:27,963 --> 05:35:28,830
MECHANICAL LOADING ACTUALLY

7919
05:35:28,830 --> 05:35:32,067
PRODUCES A RESPONSE.

7920
05:35:32,067 --> 05:35:32,768
SO, THE MECHANOSENSITIVE MOTIFS

7921
05:35:32,768 --> 05:35:34,636
WE FOUND A WHOLE BUNCH IN

7922
05:35:34,636 --> 05:35:37,039
NF-kappaB FAMILY THAT TURNED

7923
05:35:37,039 --> 05:35:42,044
OUT TO BE MECHANICALLY

7924
05:35:42,044 --> 05:35:52,554
SENSITIVE, AND OTHERS IN THE

7925
05:35:52,554 --> 05:35:54,323
SIGH CYCLOOXYGENASE.

7926
05:35:54,323 --> 05:35:56,391
AS WE ACTIVATE ION CHANNEL, OH,

7927
05:35:56,391 --> 05:35:58,493
WE CAN PUT THIS AS A VIRAL

7928
05:35:58,493 --> 05:35:59,161
VECTOR OR CRISPR.

7929
05:35:59,161 --> 05:36:02,130
THE BEAUTY IS WE DON'T HAVE TO

7930
05:36:02,130 --> 05:36:02,698
USE iPSCs.

7931
05:36:02,698 --> 05:36:07,102
WE DO BUT WE CAN ALSO PUT THEM

7932
05:36:07,102 --> 05:36:09,204
IN PRIMARY CELLS, CHONDROCYTES,

7933
05:36:09,204 --> 05:36:10,505
NERVE CELLS, ANYTHING, AS THEY

7934
05:36:10,505 --> 05:36:11,506
ARE MECHANICALLY LOADED THEY

7935
05:36:11,506 --> 05:36:16,745
GIVE OFF THIS THERAPEUTIC DRUG

7936
05:36:16,745 --> 05:36:19,915
WHICH CAN BE REPLACED WITH ANY

7937
05:36:19,915 --> 05:36:22,017
BIOLOGIC DRUG THAT'S A GENE

7938
05:36:22,017 --> 05:36:22,651
PRODUCT.

7939
05:36:22,651 --> 05:36:24,286
SO, WHEN WE DO THIS, I'LL SKIP

7940
05:36:24,286 --> 05:36:24,953
THROUGH THIS.

7941
05:36:24,953 --> 05:36:26,922
WE SHOW WE CAN LOAD THEM AND

7942
05:36:26,922 --> 05:36:28,357
WITH INCREASING LOADING THEY

7943
05:36:28,357 --> 05:36:31,927
MAKE THIS DRUG IL-1 R.A. WHICH

7944
05:36:31,927 --> 05:36:35,931
THEY DON'T MAKE  NORMALLY IN ANY

7945
05:36:35,931 --> 05:36:36,264
QUANTITY.

7946
05:36:36,264 --> 05:36:38,433
WE HAVE A CIRCUIT TO MAKE THIS

7947
05:36:38,433 --> 05:36:38,734
DRUG.

7948
05:36:38,734 --> 05:36:40,602
I'LL TELL YOU ABOUT THIS NEW

7949
05:36:40,602 --> 05:36:45,307
AREA THAT WE FEEL WE'VE

7950
05:36:45,307 --> 05:36:46,508
DEVELOPED, CHRONOGENETICS,

7951
05:36:46,508 --> 05:36:48,744
DRIVING DRUG DELIVERY FROM STEM

7952
05:36:48,744 --> 05:36:49,578
CELLS WITH TIME.

7953
05:36:49,578 --> 05:36:52,647
AND AS YOU ALL KNOW, WE HAVE OUR

7954
05:36:52,647 --> 05:36:53,949
OWN CIRCADIAN CLOCKS IN OUR

7955
05:36:53,949 --> 05:37:02,758
BRAIN, THE MAIN CLOCK, 24-CYCLE,

7956
05:37:02,758 --> 05:37:06,862
RUN BY THE SUPER CHIASMATIC

7957
05:37:06,862 --> 05:37:08,196
NUCLEUS, IT CONTROLS PERIPHERAL

7958
05:37:08,196 --> 05:37:10,732
CLOCKS IN OUR BODY.

7959
05:37:10,732 --> 05:37:12,567
VIRTUALLY EVERY CELL HAS CLOCK

7960
05:37:12,567 --> 05:37:15,003
CIRCUITS, A COMPLEX TRIPLE LOOP

7961
05:37:15,003 --> 05:37:16,905
OF ACTIVATORS AND REPRESSORS BUT

7962
05:37:16,905 --> 05:37:20,175
CORE ACTIVATORS AND REPRESSORS

7963
05:37:20,175 --> 05:37:21,443
ARE THESE TWO GENES, THEY TURN

7964
05:37:21,443 --> 05:37:31,920
ON THEIR OWN REPEER REVIEWS 

7965
05:37:34,756 --> 05:37:35,457
I OS -- REPRESSORS.

7966
05:37:35,457 --> 05:37:37,626
WHY DON'T WE USE THIS TO DELIVER

7967
05:37:37,626 --> 05:37:38,860
DRUGS AT SPECIFIC TIMES OF DAY

7968
05:37:38,860 --> 05:37:40,796
FROM OUR STEM CELLS?

7969
05:37:40,796 --> 05:37:43,532
OF ALL TISSUES, CARTILAGE HAS

7970
05:37:43,532 --> 05:37:47,302
ONE OF THE MOST STABLE AND

7971
05:37:47,302 --> 05:37:47,736
ROBUST CLOCKS.

7972
05:37:47,736 --> 05:37:50,772
ON THE RIGHT YOU SEE A MOUSE HIP

7973
05:37:50,772 --> 05:37:52,174
FROM A LUCIFERASE MOUSE, TAKEN

7974
05:37:52,174 --> 05:37:55,377
OUT OF THE MOUSE, SITTING IN A

7975
05:37:55,377 --> 05:37:57,679
BLACK BOX, WITH NO MEDIA

7976
05:37:57,679 --> 05:37:59,448
CHANGES, NO MOVEMENT, NO

7977
05:37:59,448 --> 05:37:59,681
NOTHING.

7978
05:37:59,681 --> 05:38:01,850
IT JUST CONTINUES TO CYCLE ON A

7979
05:38:01,850 --> 05:38:04,019
24-HOUR CYCLE FOR OVER A WEEK.

7980
05:38:04,019 --> 05:38:05,687
THE CELLS STAY ALIVE.

7981
05:38:05,687 --> 05:38:07,122
TURNS OUT DOWNSTREAM OF THESE

7982
05:38:07,122 --> 05:38:08,523
CLOCK GENES ARE HUNDREDS OF

7983
05:38:08,523 --> 05:38:11,026
OTHER GENES THAT ARE DRIVEN ON A

7984
05:38:11,026 --> 05:38:11,760
CIRCADIAN BASIS.

7985
05:38:11,760 --> 05:38:14,863
SO WE HAVE ALL OF THESE GENES IN

7986
05:38:14,863 --> 05:38:15,997
OUR BODY PARTICULARLY IN

7987
05:38:15,997 --> 05:38:21,970
CARTILAGE THAT GO UP AND DOWN,

7988
05:38:21,970 --> 05:38:24,072
MATRIX PROTEINS, ALL

7989
05:38:24,072 --> 05:38:25,841
INFLAMMATORY GENE CASCADES GO UP

7990
05:38:25,841 --> 05:38:27,476
AND DOWN ON THE 24-HOUR CYCLE.

7991
05:38:27,476 --> 05:38:29,444
THE TIMING OF DRUG DELIVERY AND

7992
05:38:29,444 --> 05:38:32,080
STEM CELL DELIVERY TURNS OUT TO

7993
05:38:32,080 --> 05:38:33,715
BE REALLY IMPORTANT BUT IF YOU

7994
05:38:33,715 --> 05:38:35,584
MISS THAT PEAK YOU'RE PROBABLY

7995
05:38:35,584 --> 05:38:37,285
NOT GOING TO GET AS MUCH

7996
05:38:37,285 --> 05:38:38,920
THERAPEUTIC EFFECT AS IF YOU HIT

7997
05:38:38,920 --> 05:38:41,923
IT DIRECT LIB ON THE -- DIRECT

7998
05:38:41,923 --> 05:38:43,558
LIP ON THE PEAK.

7999
05:38:43,558 --> 05:38:44,559
NEXT SLIDE PLEASE.

8000
05:38:44,559 --> 05:38:47,529
SO THIS HAS RAISED CONCEPT OF

8001
05:38:47,529 --> 05:38:50,899
CHRONOTHERAPY. 

8002
05:38:50,899 --> 05:38:52,767
TIMING DRUG DELIVERY OR THERAPY

8003
05:38:52,767 --> 05:38:54,636
TO CIRCADIAN CLOCK.

8004
05:38:54,636 --> 05:38:56,872
THERE'S GREAT DATA NOW.

8005
05:38:56,872 --> 05:38:58,874
BACK ONE PLEASE.

8006
05:38:58,874 --> 05:39:00,675
ON AUTOIMMUNE DISEASE AND PEAK

8007
05:39:00,675 --> 05:39:04,412
CYTOKINE LEVELS AS YOU SEE ON

8008
05:39:04,412 --> 05:39:06,381
THE RIGHT-MOST GRAPH, ALL HALF

8009
05:39:06,381 --> 05:39:07,782
REALLY EARLY IN THE IMPORTANT, 1

8010
05:39:07,782 --> 05:39:09,317
TO 3 IN THE MORNING.

8011
05:39:09,317 --> 05:39:11,820
NO ONE TAKES DRUGS AT 1 TO 3 IN

8012
05:39:11,820 --> 05:39:16,057
THE MORNING.

8013
05:39:16,057 --> 05:39:18,660
THIS IS WHY PEOPLE HAVE MORNING

8014
05:39:18,660 --> 05:39:21,129
STIFFNESS, THE PEAK AFTER THE

8015
05:39:21,129 --> 05:39:22,030
DRUGS.

8016
05:39:22,030 --> 05:39:24,399
ATTEMPTS WITH DELAYED DELIVERY

8017
05:39:24,399 --> 05:39:25,433
DRUGS HAVEN'T WORKED.

8018
05:39:25,433 --> 05:39:28,036
OUR THOUGHT WHY DON'T WE

8019
05:39:28,036 --> 05:39:33,842
ENGINEER  CELLS TO MAKE

8020
05:39:33,842 --> 05:39:34,509
ANTI-RHEUMATIC DRUGS AT SPECIFIC

8021
05:39:34,509 --> 05:39:36,344
TIMES OF DAY.

8022
05:39:36,344 --> 05:39:37,979
A OF iPSCs DON'T HAVE A

8023
05:39:37,979 --> 05:39:41,416
CLOCK, IF YOU DIFFERENTIAL INTO

8024
05:39:41,416 --> 05:39:47,989
A CONDO  -- CHONDROCYTE THEY

8025
05:39:47,989 --> 05:39:49,691
FORM A CLOCK.

8026
05:39:49,691 --> 05:39:51,393
USING DIFFERENT PARTS WE CAN

8027
05:39:51,393 --> 05:39:53,128
SHIFT DELIVERY BY 12 HOURS OR

8028
05:39:53,128 --> 05:39:55,697
NOW WE FIGURED OUT HOW TO DO

8029
05:39:55,697 --> 05:39:58,600
3-HOUR INCREMENTS, TO SET UP THE

8030
05:39:58,600 --> 05:40:01,236
CELLS SO THEY DELIVER DRUGS AT

8031
05:40:01,236 --> 05:40:02,837
PRESCRIBED TIMES, ONCE A DAY,

8032
05:40:02,837 --> 05:40:07,075
TWICE A DAY, OR EVERY THREE

8033
05:40:07,075 --> 05:40:07,642
HOURS.

8034
05:40:07,642 --> 05:40:09,611
WE TESTED IN MICE.

8035
05:40:09,611 --> 05:40:10,812
BASICALLY MADE IMPLANTS, PUT

8036
05:40:10,812 --> 05:40:14,082
THEM IN A MOUSE, TRACKED THEM

8037
05:40:14,082 --> 05:40:15,417
WITH LIGHT/DARK CYCLES, TOOK

8038
05:40:15,417 --> 05:40:20,021
THEIR SERUM AND LOOKED AT DRUG 

8039
05:40:20,021 --> 05:40:20,322
LEVELS.

8040
05:40:20,322 --> 05:40:22,223
NEXT SLIDE.

8041
05:40:22,223 --> 05:40:24,492
WE FOUND 6 TO 10 TIMES INCREASE

8042
05:40:24,492 --> 05:40:28,063
IN DRUG AT THE PEAK CLOCK HOURS

8043
05:40:28,063 --> 05:40:33,802
WHEN WE SWITCH THE DAYLIGHT ON

8044
05:40:33,802 --> 05:40:39,374
MICE,  SYNCHRONIZE AND KEEP UP.

8045
05:40:39,374 --> 05:40:42,377
TO CONCLUDE, YOU CAN SEE HOW WE

8046
05:40:42,377 --> 05:40:47,282
CAN TAKE STEM CELLS, iPSCs,

8047
05:40:47,282 --> 05:40:48,984
EDIT GENOME, EDIT EPIGENOMEI

8048
05:40:48,984 --> 05:40:50,986
IT'S PUBLISHED, CREATE GENE

8049
05:40:50,986 --> 05:40:53,188
CIRCUITS, REPACKAGE AS CELL

8050
05:40:53,188 --> 05:40:54,756
THERAPY, GENE THERAPY, IMPLANT

8051
05:40:54,756 --> 05:40:56,992
THERAPY, AND HOPEFULLY ONE DAY

8052
05:40:56,992 --> 05:41:05,100
MAYBE EVEN A MULTI-IMPLANT

8053
05:41:05,100 --> 05:41:05,767
THERAPY.

8054
05:41:05,767 --> 05:41:06,935
QUESTIONS THAT COME UP, THE SAME

8055
05:41:06,935 --> 05:41:08,470
QUESTIONS WE'VE BEEN TALKING

8056
05:41:08,470 --> 05:41:12,040
ABOUT. 

8057
05:41:12,040 --> 05:41:16,111
CAN WE CREATE CUSTOM DESIGNED

8058
05:41:16,111 --> 05:41:16,878
CELLS?

8059
05:41:16,878 --> 05:41:18,580
SOME CAN BE DELIVERED AS

8060
05:41:18,580 --> 05:41:27,756
NON-CELL THERAPIES TO  TO

8061
05:41:27,756 --> 05:41:28,289
AUTOGENOUS CELLS.

8062
05:41:28,289 --> 05:41:29,290
GENE THERAPIES ARE AFFECTING

8063
05:41:29,290 --> 05:41:31,760
CELLS BUT NOT A CELL THERAPY PER

8064
05:41:31,760 --> 05:41:33,328
SE.

8065
05:41:33,328 --> 05:41:35,597
QUELLS FOR THESE CELLS ARE

8066
05:41:35,597 --> 05:41:37,599
PRIMARILY SAFETY AND EFFICACY,

8067
05:41:37,599 --> 05:41:39,000
QUALITY ASSURANCE AND SCALEUP,

8068
05:41:39,000 --> 05:41:40,468
WE'RE WORKING ON A SINGLE CELL

8069
05:41:40,468 --> 05:41:42,604
BANK THAT'S EDITED SO WE CAN DO

8070
05:41:42,604 --> 05:41:46,908
A LOT OF THAT ALLOGENEICALLY

8071
05:41:46,908 --> 05:41:48,009
OFFLINE BUT REGULATORY ISSUES

8072
05:41:48,009 --> 05:41:49,844
ARE CRITICAL HERE.

8073
05:41:49,844 --> 05:41:55,517
IT'S PROBABLY  A COMBINATION

8074
05:41:55,517 --> 05:41:58,353
PRODUCT BUT CELLS THEMSELVES, WE

8075
05:41:58,353 --> 05:42:00,522
TALKED ABOUT CRISPR OFF-TARGET

8076
05:42:00,522 --> 05:42:06,594
EFFECT, WHICH CELLS, HOW DO WE

8077
05:42:06,594 --> 05:42:07,028
DELIVER.

8078
05:42:07,028 --> 05:42:09,264
WE'VE DEVELOPED GELS THAT WE CAN

8079
05:42:09,264 --> 05:42:10,965
INJECT TO MAINTAIN THE CELLS AND

8080
05:42:10,965 --> 05:42:21,476
THEN  CELL THERAPY AND COST IS

8081
05:42:21,810 --> 05:42:23,545
AN ISSUE.

8082
05:42:23,545 --> 05:42:24,345
I THANK THE COLLABORATORS,

8083
05:42:24,345 --> 05:42:26,247
PEOPLE IN THE LABORATORY AND

8084
05:42:26,247 --> 05:42:28,049
FUNDING, AND HAPPY TO ANSWER

8085
05:42:28,049 --> 05:42:38,493
QUESTIONS IF WE HAVE TIME.

8086
05:42:45,467 --> 05:42:52,207
>> [OFF MICROPHONE].

8087
05:42:52,207 --> 05:42:53,374
>> CONGRATULATIONS ON THE

8088
05:42:53,374 --> 05:42:54,709
ADVANCES YOU MADE.

8089
05:42:54,709 --> 05:42:56,945
I LOVE THE IDEA OF WHERE YOU

8090
05:42:56,945 --> 05:42:59,514
SHOWED DOING DRUG DELIVERY IN

8091
05:42:59,514 --> 05:43:01,716
CARTILAGE BUT I WONDER WHETHER

8092
05:43:01,716 --> 05:43:02,817
IT'S WORTH THINKING GRANDIOSELY,

8093
05:43:02,817 --> 05:43:05,320
ESPECIALLY FOR THE SAKE OF

8094
05:43:05,320 --> 05:43:06,855
CONSORTIUM, WHAT IF THERE WAS A

8095
05:43:06,855 --> 05:43:10,692
CELL LINE THAT COULD BE MADE FOR

8096
05:43:10,692 --> 05:43:11,793
UNIVERSAL SYSTEMIC DRUG DELIVERY

8097
05:43:11,793 --> 05:43:13,962
AND DRUG COMPANIES ALL THEY HAD

8098
05:43:13,962 --> 05:43:16,264
TO DO WAS CLONE INTO MULTIPLE

8099
05:43:16,264 --> 05:43:17,499
CLONING SITE PROTEIN THEY WANT

8100
05:43:17,499 --> 05:43:19,134
TO DELIVER AND MAYBE PROMOTER

8101
05:43:19,134 --> 05:43:23,171
THEY WANT TO -- THAT WOULD

8102
05:43:23,171 --> 05:43:24,773
TRIGGER THAT EXPRESSION,

8103
05:43:24,773 --> 05:43:25,473
THINKING GENERALLY OF THE

8104
05:43:25,473 --> 05:43:26,374
APPROACH YOU STARTED.

8105
05:43:26,374 --> 05:43:28,543
WHAT ARE YOUR THOUGHTS ON THAT.

8106
05:43:28,543 --> 05:43:28,777
>> .

8107
05:43:28,777 --> 05:43:29,744
>> FABULOUS IDEA.

8108
05:43:29,744 --> 05:43:32,080
WE HAVE SOME BASE TECHNOLOGIES,

8109
05:43:32,080 --> 05:43:34,215
IT'S NOT AS PERFECT AS YOU'RE

8110
05:43:34,215 --> 05:43:34,516
DESCRIBING.

8111
05:43:34,516 --> 05:43:35,850
I KNOW WHAT YOU'RE SAYING, PLUG

8112
05:43:35,850 --> 05:43:37,051
AND PLAY.

8113
05:43:37,051 --> 05:43:40,021
WE HAVE THIS PROMOTER SITE, THIS

8114
05:43:40,021 --> 05:43:42,824
AMPLIFIER, MY BACKGROUND IS

8115
05:43:42,824 --> 05:43:44,692
ENGINEERING SO CIRCUITS AND

8116
05:43:44,692 --> 05:43:46,661
AMPLIFIERS.

8117
05:43:46,661 --> 05:43:47,896
WE CAN INSERT THESE.

8118
05:43:47,896 --> 05:43:49,964
WE'RE DOING THAT BUT IT'S SUCH A

8119
05:43:49,964 --> 05:43:51,599
LONG PROCESS WITH ALL THIS

8120
05:43:51,599 --> 05:43:53,668
ASSURANCE THAT WE GET IT RIGHT.

8121
05:43:53,668 --> 05:43:55,436
AND SO THERE MAY BE VIRAL

8122
05:43:55,436 --> 05:43:59,440
TECHNIQUES, SOMEONE WAS TALKING

8123
05:43:59,440 --> 05:44:01,810
ABOUT USING LENTIVIRUS TO GET

8124
05:44:01,810 --> 05:44:03,645
THINGS INTO CELLS QUICKLY,

8125
05:44:03,645 --> 05:44:07,415
BEFORE THE ONE-YEAR PROCESS OF

8126
05:44:07,415 --> 05:44:08,950
CRISPR-ING THEM IN.

8127
05:44:08,950 --> 05:44:10,485
IT'S PLUG AND PLAY, DIFFERENT

8128
05:44:10,485 --> 05:44:13,221
FOR DIFFERENT CELLS.

8129
05:44:13,221 --> 05:44:14,422
MOI, YOUR TRANSDUCTION

8130
05:44:14,422 --> 05:44:15,590
EFFICIENCIES AND EVERYTHING, BUT

8131
05:44:15,590 --> 05:44:17,025
I LOVE THE CONCEPT.

8132
05:44:17,025 --> 05:44:18,993
IF WE CAN GET DO THAT, MAYBE WE

8133
05:44:18,993 --> 05:44:21,196
CAN DISCUSS MORE HOW TO GET TO

8134
05:44:21,196 --> 05:44:23,298
THAT, THAT WE HAVE SORT OF ALL

8135
05:44:23,298 --> 05:44:28,069
OF THE PARTS AND THEN YOU CAN

8136
05:44:28,069 --> 05:44:31,573
JUST PUT IN YOUR

8137
05:44:31,573 --> 05:44:32,407
STIMULUS/RESPONSE.

8138
05:44:32,407 --> 05:44:35,510
>> SO, TO FOLLOW UP ON THE

8139
05:44:35,510 --> 05:44:37,612
CIRCADIAN ASPECT, FASCINATING.

8140
05:44:37,612 --> 05:44:40,515
I WONDER IF THINKING BROADLY IF

8141
05:44:40,515 --> 05:44:44,052
YOU LOOK AT DISEASES THAT HAVE

8142
05:44:44,052 --> 05:44:46,554
BEEN TARGETED FOR CELL-BASED

8143
05:44:46,554 --> 05:44:48,256
THERAPIES, THINK, FOR EXAMPLE,

8144
05:44:48,256 --> 05:44:50,258
ANOTHER CHRONIC INFLAMMATORY

8145
05:44:50,258 --> 05:44:51,059
STATE LIKE GRAFT-VERSUS-HOST

8146
05:44:51,059 --> 05:44:53,595
DISEASE, IS THERE EVIDENCE

8147
05:44:53,595 --> 05:44:55,997
THERE'S A CIRCADIAN ASPECT TO

8148
05:44:55,997 --> 05:44:57,332
THAT, AND THEN THE PARALLEL

8149
05:44:57,332 --> 05:45:01,135
QUESTION IS WHETHER OR NOT IN AN

8150
05:45:01,135 --> 05:45:02,136
ACUTE HYPERINTENSE INFLAMMATORY

8151
05:45:02,136 --> 05:45:05,206
STATE, LET'S SAY SEPTIC SHOCK OR

8152
05:45:05,206 --> 05:45:08,042
ARDS, IS THERE STILL A CIRCADIAN

8153
05:45:08,042 --> 05:45:09,978
ASPECT?

8154
05:45:09,978 --> 05:45:11,646
BECAUSE THIS LETS US RETHINK HOW

8155
05:45:11,646 --> 05:45:22,056
WE APPLY CELL THERAPIES?

8156
05:45:26,427 --> 05:45:29,497
>> BECAUSE THE CLOCK IS
GOING UP

8157
05:45:29,497 --> 05:45:30,365
AND DOWN, HUNDREDS OF GENES,

8158
05:45:30,365 --> 05:45:31,966
MAIN DRIVER GENES ARE GOING UP

8159
05:45:31,966 --> 05:45:35,103
AND DOWN, IT'S A QUESTION OF THE

8160
05:45:35,103 --> 05:45:36,537
EXTENT.

8161
05:45:36,537 --> 05:45:47,081
BUT GREAT STUDY MY COLLABORATOR

8162
05:45:48,683 --> 05:45:50,018
DID, GLIOBLASTOMA, FOUR MONTH

8163
05:45:50,018 --> 05:45:52,220
HIGHER SURVIVAL IN 10 A.M., SAME

8164
05:45:52,220 --> 05:45:53,354
DRUG, EVERYTHING ELSE.

8165
05:45:53,354 --> 05:45:54,555
THE TUMOR IS CYCLING.

8166
05:45:54,555 --> 05:45:56,024
THE BODY IS CYCLING.

8167
05:45:56,024 --> 05:45:57,659
I'M SURE ANY OTHER INFLAMMATORY

8168
05:45:57,659 --> 05:45:59,427
PROCESSES ARE GOING TO BE

8169
05:45:59,427 --> 05:45:59,994
CYCLING.

8170
05:45:59,994 --> 05:46:00,995
WE NEED TO DECONSTRUCT TO SAY

8171
05:46:00,995 --> 05:46:04,365
WHEN DO YOU WANT TO DELIVER

8172
05:46:04,365 --> 05:46:06,634
WHAT?

8173
05:46:06,634 --> 05:46:12,707
 

8174
05:46:12,707 --> 05:46:22,750
 

8175
05:46:23,418 --> 05:46:23,484
 

8176
05:46:23,484 --> 05:46:25,420
WE BUILT BOTH HALFS, BOTH AT THE

8177
05:46:25,420 --> 05:46:27,188
SAME TIME.

8178
05:46:27,188 --> 05:46:28,623
TURNS OUT MECHANICAL LOADS RESET

8179
05:46:28,623 --> 05:46:29,290
THE CLOCK.

8180
05:46:29,290 --> 05:46:31,292
GETTING UP AND WALKING AROUND IN

8181
05:46:31,292 --> 05:46:32,093
THE MORNING RESYNCHRONIZES THE

8182
05:46:32,093 --> 05:46:34,195
CLOCK IN YOUR JOINTS AND GETS

8183
05:46:34,195 --> 05:46:35,496
EVERYTHING SORT OF HEALTHY AND

8184
05:46:35,496 --> 05:46:36,931
GOING AGAIN WHICH IS ANOTHER

8185
05:46:36,931 --> 05:46:38,766
REASON EXERCISE IS GOOD.

8186
05:46:38,766 --> 05:46:40,201
IT'S OBVIOUSLY LIKE EVERYTHING

8187
05:46:40,201 --> 05:46:42,637
ELSE, WAY MORE COMPLICATED THAN

8188
05:46:42,637 --> 05:46:44,138
WE HOPED INITIALLY BUT ALSO

8189
05:46:44,138 --> 05:46:45,773
MAKES IT REALLY INTERESTING THAT

8190
05:46:45,773 --> 05:46:48,443
YOU HAVE MULTIPLE TARGETS TO GO

8191
05:46:48,443 --> 05:46:48,643
AFTER.

8192
05:46:48,643 --> 05:46:51,412
AND THEY SEEM TO BE AT LEAST

8193
05:46:51,412 --> 05:46:52,380
ADDITIVE IF NOT SYNERGISTIC.

8194
05:46:52,380 --> 05:46:55,283
WE DON'T HAVE TO GET ALL, BUT

8195
05:46:55,283 --> 05:46:58,686
EVEN ONE PART OF THAT DYNAMIC

8196
05:46:58,686 --> 05:47:01,222
CHANGE IN INFLAMMATION WILL BE

8197
05:47:01,222 --> 05:47:01,823
HELPFUL.

8198
05:47:01,823 --> 05:47:05,159
IF WE GET BOTH PARTS THAT THE

8199
05:47:05,159 --> 05:47:05,593
EVEN BETTER.

8200
05:47:05,593 --> 05:47:07,061
>> FABULOUS WORK.

8201
05:47:07,061 --> 05:47:10,298
I'D LOVE TO DIVE MORE INTO IT.

8202
05:47:10,298 --> 05:47:13,201
BROADER QUESTION, YOU MENTIONED

8203
05:47:13,201 --> 05:47:14,135
THE VARIABILITY WITH iPSC,

8204
05:47:14,135 --> 05:47:17,772
WHICH IS GOING TO MIRROR THAT --

8205
05:47:17,772 --> 05:47:18,840
THE DONORS.

8206
05:47:18,840 --> 05:47:21,376
AND JUST WONDERING, WHAT IS THE

8207
05:47:21,376 --> 05:47:22,443
DEGREE OF VARIABILITY AND ARE

8208
05:47:22,443 --> 05:47:26,748
YOU LOOKING AT THESE FOR

8209
05:47:26,748 --> 05:47:28,516
AUTOLOGOUS APPLICATIONS?

8210
05:47:28,516 --> 05:47:31,753
PERSONALIZED ENGINEERING OR ARE

8211
05:47:31,753 --> 05:47:35,356
YOU LOOKING INTO MORE SIMILAR TO

8212
05:47:35,356 --> 05:47:37,325
AN ALLOGENEIC OR UNIVERSAL

8213
05:47:37,325 --> 05:47:37,692
ENGINEERED CELL?

8214
05:47:37,692 --> 05:47:38,860
>> GREAT QUESTION.

8215
05:47:38,860 --> 05:47:40,962
WE'VE MADE THE DECISION THAT FOR

8216
05:47:40,962 --> 05:47:43,698
IT TO BE CLOSE TO -- IN CURRENT

8217
05:47:43,698 --> 05:47:45,833
SYSTEM, CLOSE TO BEING TIME

8218
05:47:45,833 --> 05:47:47,201
EFFECTIVE, COST EFFECTIVE, WE

8219
05:47:47,201 --> 05:47:49,704
HAVE TO HAVE A TESTING

8220
05:47:49,704 --> 05:47:50,071
ALLOGENEIC CELL.

8221
05:47:50,071 --> 05:47:51,739
IT WAS PART OF THE DISCUSSION

8222
05:47:51,739 --> 05:47:54,976
EARLIER, WHERE WE CAN DO ALL OF

8223
05:47:54,976 --> 05:47:56,044
THESE EDITS, DO, YOU KNOW,

8224
05:47:56,044 --> 05:47:58,546
SEQUENCING TO SHOW WE DON'T HAVE

8225
05:47:58,546 --> 05:48:01,416
OFF TARGET EFFECTS, RUB IT --

8226
05:48:01,416 --> 05:48:02,617
RUN IT THROUGH A PROCESS AND

8227
05:48:02,617 --> 05:48:03,384
SCALE UP.

8228
05:48:03,384 --> 05:48:07,855
IF WE HAD TO DO AT THIS POINT

8229
05:48:07,855 --> 05:48:09,157
AUTOLOGOUS EDITED iPSC FOR

8230
05:48:09,157 --> 05:48:10,525
THIS TYPE, IT WOULD BE COST

8231
05:48:10,525 --> 05:48:20,802
PROHIBIT I CAN. 

8232
05:48:25,206 --> 05:48:29,010
POET-- PROHIBITIVE. 

8233
05:48:29,010 --> 05:48:29,644
ALLOGENEIC UNLESS GREAT

8234
05:48:29,644 --> 05:48:31,746
TECHNOLOGY COMES THROUGH.

8235
05:48:31,746 --> 05:48:33,014
FOR OUR APPLICATIONS, WE USE

8236
05:48:33,014 --> 05:48:35,116
LARGE LOTS OF CELLS, GET A NICE

8237
05:48:35,116 --> 05:48:38,519
AVERAGE, HAVE MILLIONS OF CELLS

8238
05:48:38,519 --> 05:48:39,954
WHERE WE SEE HOMOGENEITY POP UP

8239
05:48:39,954 --> 05:48:41,489
IN DIFFERENTIATION.

8240
05:48:41,489 --> 05:48:43,991
IF WE TAKE iPSCs ANDS HUMAN

8241
05:48:43,991 --> 05:48:45,860
ONES, HIT THE ENTIRE DISH WITH

8242
05:48:45,860 --> 05:48:51,399
ALL OUR FAVORITE GROWTH FACTORS,

8243
05:48:51,399 --> 05:48:54,502
YOU GET SOME CHONDROCYTES,

8244
05:48:54,502 --> 05:49:03,811
NEUROGENESIS, AND THEN OUR 

8245
05:49:03,811 --> 05:49:05,746
PALATES GROW MY ANOCYTES.

8246
05:49:05,746 --> 05:49:08,416
THEY ARE ALREADY EPIGENETICALLY

8247
05:49:08,416 --> 05:49:09,383
GOING DIFFERENT DIRECTIONS, AND

8248
05:49:09,383 --> 05:49:11,018
WE'RE FINDING WAYS TO GET OVER

8249
05:49:11,018 --> 05:49:15,990
THAT, BUT JUST TO KNOW YOUR 

8250
05:49:15,990 --> 05:49:17,358
STARTING CELL IS

8251
05:49:17,358 --> 05:49:21,429
EPIGENETICALLY -- BOTH FROM

8252
05:49:21,429 --> 05:49:22,096
RNAseq BUT ATAC-SEQ

8253
05:49:22,096 --> 05:49:25,399
MEASUREMENTS, DIVERSE WHEN YOU

8254
05:49:25,399 --> 05:49:28,436
FIRST START.

8255
05:49:28,436 --> 05:49:28,970
>> THE FINAL QUESTION [OFF

8256
05:49:28,970 --> 05:49:36,043
MICROPHONE].

8257
05:49:36,043 --> 05:49:39,313
>> THAT'S A GREAT
QUESTION.

8258
05:49:39,313 --> 05:49:42,550
AND, YOU KNOW, I THINK IF WE

8259
05:49:42,550 --> 05:49:45,653
KNOW SOME BIOLOGIC DRIVERS, AND

8260
05:49:45,653 --> 05:49:46,354
INHIBITORS OF SENESCENCE, I

8261
05:49:46,354 --> 05:49:48,689
DON'T SEE WHY YOU COULDN'T.

8262
05:49:48,689 --> 05:49:50,591
IT'S ALMOST ANY BIOLOGIC

8263
05:49:50,591 --> 05:49:52,860
FEEDBACK LOOP, IF WE KNOW IT, WE

8264
05:49:52,860 --> 05:49:54,629
CAN TINKER WITH IT, RIGHT?

8265
05:49:54,629 --> 05:49:58,232
LIKE DIABETES IS A GREAT TARGET,

8266
05:49:58,232 --> 05:49:59,834
BASICALLY WHAT IT IS ALREADY.

8267
05:49:59,834 --> 05:50:02,236
IF WE KNOW FEEDBACK LOOP FOR

8268
05:50:02,236 --> 05:50:04,172
SENESCENCE, IT'S LIKE EVERYTHING

8269
05:50:04,172 --> 05:50:05,640
ELSE, YOU DON'T WANT TO

8270
05:50:05,640 --> 05:50:06,974
COMPLETELY SHUT IT OFF, WHY

8271
05:50:06,974 --> 05:50:08,943
HAVING A CONTROLLED LOOP IS

8272
05:50:08,943 --> 05:50:10,278
BETTER THAN BLASTING IT WITH

8273
05:50:10,278 --> 05:50:10,478
DRUGS.

8274
05:50:10,478 --> 05:50:11,679
SO THAT'S A GREAT IDEA.

8275
05:50:11,679 --> 05:50:16,584
WE SHOULD TALK MORE. 

8276
05:50:16,584 --> 05:50:17,218
>> GREAT.

8277
05:50:17,218 --> 05:50:19,654
>> QUICK QUESTION, AND
QUICK

8278
05:50:19,654 --> 05:50:20,054
COMMENT.

8279
05:50:20,054 --> 05:50:26,661
WHEN YOU TAKE THE EXPLANT OF

8280
05:50:26,661 --> 05:50:28,095
CARTAGE, STILL LIGHTING UP FOR

8281
05:50:28,095 --> 05:50:30,164
SEVEN DAYS, AFTER THAT THE CELLS

8282
05:50:30,164 --> 05:50:32,133
FOLLOW THEIR OWN PATH?

8283
05:50:32,133 --> 05:50:36,971
OR DOES THE EXPLANT REMAIN

8284
05:50:36,971 --> 05:50:37,505
SYNCHRONIZE.

8285
05:50:37,505 --> 05:50:39,240
>> THEY SLOWLY START TO

8286
05:50:39,240 --> 05:50:39,674
DESYNCHRONIZE.

8287
05:50:39,674 --> 05:50:41,108
IT'S A HARD EXPERIMENT TO GO

8288
05:50:41,108 --> 05:50:42,610
PATH THAT AMOUNT OF TIME BECAUSE

8289
05:50:42,610 --> 05:50:44,912
YOU HAVE TO CHANGE THE MEDIA AT

8290
05:50:44,912 --> 05:50:45,580
SOME POINT.

8291
05:50:45,580 --> 05:50:49,717
AND THE SHOCK OF CHANGING THE 

8292
05:50:49,717 --> 05:50:58,960
MEDIA WILL OFTEN RESYNCHRONIZE

8293
05:50:58,960 --> 05:51:00,795
OR PARTIALLY RESYNCHRONIZE, SO

8294
05:51:00,795 --> 05:51:01,762
PLAYING AROUND MAKES IT

8295
05:51:01,762 --> 05:51:02,730
DIFFICULT TO STUDY THEM PAST

8296
05:51:02,730 --> 05:51:05,266
THAT TIME POINT BUT THEY JUST

8297
05:51:05,266 --> 05:51:07,668
START TO SLOWLY GET OFF CYCLE SO

8298
05:51:07,668 --> 05:51:11,105
THAT PEAK STARTS TO BECOME MORE

8299
05:51:11,105 --> 05:51:12,807
OF A -- SMOOTHER.

8300
05:51:12,807 --> 05:51:14,075
IT'S REALLY INTERESTING.

8301
05:51:14,075 --> 05:51:15,910
IT'S THE WORST EXPERIMENT FOR A

8302
05:51:15,910 --> 05:51:17,578
GRADUATE STUDENT TO TAKE

8303
05:51:17,578 --> 05:51:21,616
THREE-HOUR TIME POINTS FOR 72

8304
05:51:21,616 --> 05:51:22,049
HOURS.

8305
05:51:22,049 --> 05:51:25,119
MY STUDENT DID THAT TWICE.

8306
05:51:25,119 --> 05:51:32,026
SHE SLEPT IN THE LAB THOSE THREE

8307
05:51:32,026 --> 05:51:32,226
DAYS.

8308
05:51:32,226 --> 05:51:34,629
>> A COMMENT, HEART
ATTACKS ALSO

8309
05:51:34,629 --> 05:51:36,063
HAPPEN MORE OFTEN IN THE EARLY

8310
05:51:36,063 --> 05:51:38,266
MORNING, EARLY HOURS OF THE

8311
05:51:38,266 --> 05:51:38,733
MORNING.

8312
05:51:38,733 --> 05:51:39,567
SO ALSO MAYBE SOMETHING TO THINK

8313
05:51:39,567 --> 05:51:41,636
ABOUT IN THE BACK OF YOUR MIND

8314
05:51:41,636 --> 05:51:42,837
AS YOU'RE MANIPULATING THESE

8315
05:51:42,837 --> 05:51:43,204
THINGS.

8316
05:51:43,204 --> 05:51:45,706
MAYBE IT COULD BE ANOTHER

8317
05:51:45,706 --> 05:51:47,508
BENEFIT.

8318
05:51:47,508 --> 05:51:49,744
>> YEAH, EXACTLY.

8319
05:51:49,744 --> 05:51:50,945
THERE'S SO MANY

8320
05:51:50,945 --> 05:51:51,979
CHRONOTHERAPEUTIC POSSIBILITIES.

8321
05:51:51,979 --> 05:51:54,782
WE DON'T EVEN KNOW ALL OF THEM.

8322
05:51:54,782 --> 05:51:56,517
SOME MIGHT JUST BE ACCIDENTAL,

8323
05:51:56,517 --> 05:51:57,718
BUT JUST ONE LAST COMMENT, SHIFT

8324
05:51:57,718 --> 05:51:59,387
WORK IS ONE OF THE WORST THINGS

8325
05:51:59,387 --> 05:52:00,688
YOU CAN DO.

8326
05:52:00,688 --> 05:52:02,690
WHEN YOU TOTALLY DISRUPT YOUR

8327
05:52:02,690 --> 05:52:04,058
CYCLE, PEOPLE WHO DO SHIFT WORK

8328
05:52:04,058 --> 05:52:05,926
ARE BEING SHOWN TO BE AT HIGHER

8329
05:52:05,926 --> 05:52:08,663
RISK FOR VIRTUALLY EVERY

8330
05:52:08,663 --> 05:52:18,105
DISEASE, WE JUST MINED  THE U.K.

8331
05:52:18,105 --> 05:52:19,740
BIOBANK, INCREASE FOR OBESITY,

8332
05:52:19,740 --> 05:52:21,475
ALL THESE OTHER THINGS FOR SHIFT

8333
05:52:21,475 --> 05:52:23,010
WORK.

8334
05:52:23,010 --> 05:52:24,111
>> OKAY.

8335
05:52:24,111 --> 05:52:26,814
SO THE FINAL SPEAKER IN THE

8336
05:52:26,814 --> 05:52:28,049
SESSION DOESN'T NEED ANY

8337
05:52:28,049 --> 05:52:35,389
INTRODUCTION EITHER.

8338
05:52:35,389 --> 05:52:37,491
DR. TONY ATALA, WAKE FOREST.

8339
05:52:37,491 --> 05:52:41,529
HE IS THE DIRECTOR OF WAKE

8340
05:52:41,529 --> 05:52:42,330
FOREST INSTITUTE FOR

8341
05:52:42,330 --> 05:52:44,799
REGENERATIVE MEDICINE.

8342
05:52:44,799 --> 05:52:46,133
 

8343
05:52:46,133 --> 05:52:47,134
>> THANK YOU.

8344
05:52:47,134 --> 05:52:48,636
GREAT TO SEE YOU.

8345
05:52:48,636 --> 05:52:51,505
GREAT TO SEE GOOD FRIENDS AND

8346
05:52:51,505 --> 05:52:54,342
COLLEAGUES AND THANK YOU FOR

8347
05:52:54,342 --> 05:52:54,809
THIS KIND INVITATION.

8348
05:52:54,809 --> 05:52:56,610
WHAT I THOUGHT I WOULD DO IS

8349
05:52:56,610 --> 05:52:58,179
GIVE AN OVERVIEW OF THE WORK

8350
05:52:58,179 --> 05:53:00,381
WE'VE BEEN DOING WITH

8351
05:53:00,381 --> 05:53:01,749
TISSUE-SPECIFIC CELLS, TALK

8352
05:53:01,749 --> 05:53:02,683
ABOUT THE OPPORTUNITIES AND

8353
05:53:02,683 --> 05:53:03,551
CHALLENGES.

8354
05:53:03,551 --> 05:53:06,320
THIS IS A PICTURE OF OUR

8355
05:53:06,320 --> 05:53:06,854
INSTITUTE.

8356
05:53:06,854 --> 05:53:08,322
IT'S THE WHOLE BUILDING

8357
05:53:08,322 --> 05:53:12,326
DEDICATED TO THE INSTITUTE.

8358
05:53:12,326 --> 05:53:15,296
WE HAVE ROUGHLY LAST COUNT OVER

8359
05:53:15,296 --> 05:53:17,331
500 PEOPLE WORKING TOGETHER TO

8360
05:53:17,331 --> 05:53:22,169
BRING TECHNOLOGY TO THE BEDSIDE.

8361
05:53:22,169 --> 05:53:23,270
PRIMARY APPOINTMENT OF FACULTY

8362
05:53:23,270 --> 05:53:27,208
IS AT THE INSTITUTE.

8363
05:53:27,208 --> 05:53:28,376
SO, AND THEN CROSS-APPOINTMENT

8364
05:53:28,376 --> 05:53:30,010
IS ANOTHER DEPARTMENT SO YOU CAN

8365
05:53:30,010 --> 05:53:31,479
WORK WELL TOGETHER.

8366
05:53:31,479 --> 05:53:34,448
WE DO EVERYTHING FROM IDEA TO

8367
05:53:34,448 --> 05:53:35,549
PROOF-OF-CONCEPT TO PRE-CLINICAL

8368
05:53:35,549 --> 05:53:39,820
WORK IN ANIMAL STUDIES TO GMP

8369
05:53:39,820 --> 05:53:41,789
MANUFACTURING FACILITY WHICH IS

8370
05:53:41,789 --> 05:53:43,524
AN FDA COMPLIANT FACILITY AND

8371
05:53:43,524 --> 05:53:45,393
RUN CLINICAL TRIALS FROM THIS

8372
05:53:45,393 --> 05:53:46,160
FACILITY, OUR OWN CLINICAL TRIAL

8373
05:53:46,160 --> 05:53:49,263
GROUP THAT RUNS THE TRIALS AND

8374
05:53:49,263 --> 05:53:49,997
COORDINATES TRIALS THROUGHOUT

8375
05:53:49,997 --> 05:53:52,967
THE U.S.

8376
05:53:52,967 --> 05:53:57,805
SO, WHEN WE TALK ABOUT REGEN

8377
05:53:57,805 --> 05:54:00,107
MED, USING CELLS ALONE, AND A

8378
05:54:00,107 --> 05:54:01,642
COUPLE SLIDES TALKED ABOUT, YOU

8379
05:54:01,642 --> 05:54:06,547
KNOW, THE  USE OF OTHER STEM

8380
05:54:06,547 --> 05:54:08,549
CELLS BUT I DELETED THEM KNOWING

8381
05:54:08,549 --> 05:54:09,316
YOU WERE SPEAKING.

8382
05:54:09,316 --> 05:54:14,655
AND WE HAVE TO DEAL WITH PLACEBO

8383
05:54:14,655 --> 05:54:15,523
EFFECT, ABOUT 35%.

8384
05:54:15,523 --> 05:54:21,862
THAT'S CHALLENGES WITH THESE

8385
05:54:21,862 --> 05:54:22,663
UNDIFFERENTIATED CELLS.

8386
05:54:22,663 --> 05:54:27,368
MY FOCUS IS  ORGAN SPECIFIC

8387
05:54:27,368 --> 05:54:28,569
CELLS, INCORPORATED INTO TISSUE

8388
05:54:28,569 --> 05:54:30,538
ITSELF AS OPPOSED TO GOING

8389
05:54:30,538 --> 05:54:32,106
THROUGH THE TISSUES IN THE BODY.

8390
05:54:32,106 --> 05:54:34,041
SO THIS IS SOME EXAMPLES OF

8391
05:54:34,041 --> 05:54:35,910
TECHNOLOGIES WE HAVE PURSUED.

8392
05:54:35,910 --> 05:54:38,045
I'D LIKE TO TELL YOU CHALLENGES

8393
05:54:38,045 --> 05:54:40,414
AND OPPORTUNITIES FOR THESE.

8394
05:54:40,414 --> 05:54:44,752
BASICALLY WE'VE DONE WORK WITH

8395
05:54:44,752 --> 05:54:45,386
SKELETAL MUSCLE.

8396
05:54:45,386 --> 05:54:48,489
WE GO BACK MANY YEARS WITH THESE

8397
05:54:48,489 --> 05:54:49,323
TECHNOLOGIES, TECHNOLOGY

8398
05:54:49,323 --> 05:54:50,891
APPROACH WE TOOK ON EARLY ON WAS

8399
05:54:50,891 --> 05:54:54,395
TO TAKE A MUSCLE BIOPSY FROM THE

8400
05:54:54,395 --> 05:54:56,664
PATIENT, EXTEND THE CELLS

8401
05:54:56,664 --> 05:54:57,798
OUTSIDE THE BODY, PLACE CELLS

8402
05:54:57,798 --> 05:55:00,267
RIGHT BACK INTO THE PATIENT.

8403
05:55:00,267 --> 05:55:02,369
WE'VE DONE NOW THAT FOR MANY

8404
05:55:02,369 --> 05:55:03,270
DIFFERENT APPLICATIONS USING

8405
05:55:03,270 --> 05:55:05,639
DIFFERENT STRATEGIES BUT THE

8406
05:55:05,639 --> 05:55:06,974
FIRST TO GET THE CRITERIA DOWN

8407
05:55:06,974 --> 05:55:08,843
FOR THE CELLS TO MAKE SURE WE

8408
05:55:08,843 --> 05:55:10,911
HAD THE RIGHT CELLS AND RIGHT

8409
05:55:10,911 --> 05:55:12,379
POPULATION, IT TOOK 25 YEARS TO

8410
05:55:12,379 --> 05:55:14,515
GET THESE CELLS INTO PATIENTS.

8411
05:55:14,515 --> 05:55:16,617
ONE OF THE CHALLENGES WAS ANIMAL

8412
05:55:16,617 --> 05:55:18,419
MODELS, BECAUSE THE PROBLEM IS

8413
05:55:18,419 --> 05:55:20,788
SMALL ANIMAL MODELS DO NOT

8414
05:55:20,788 --> 05:55:21,522
REFLECT PATIENT OUTCOMES.

8415
05:55:21,522 --> 05:55:24,058
YOU HAVE TO GO TO LARGE ANIMAL

8416
05:55:24,058 --> 05:55:26,760
MODELS, WE SPENT A LOT OF TIME

8417
05:55:26,760 --> 05:55:29,864
WORKING ON THESE ANIMAL MODELS,

8418
05:55:29,864 --> 05:55:33,901
MODELS FROM THE TURN OF THE

8419
05:55:33,901 --> 05:55:36,470
CENTURY, 2000s, SO WE RESECTED

8420
05:55:36,470 --> 05:55:46,947
ENTIRE SEGMENT OF THE SPHINCTER

8421
05:55:46,947 --> 05:55:47,915
CIRCUMFERENTIALLY.

8422
05:55:47,915 --> 05:55:50,117
THIS SHOWS THE CANINE MODEL.

8423
05:55:50,117 --> 05:55:53,921
YOU CAN SEE THE SAME THING IN

8424
05:55:53,921 --> 05:55:56,891
THE CYSTOGRAM WHERE THE MRI AND

8425
05:55:56,891 --> 05:55:58,192
NERVE STIMULATION, CONSISTENT

8426
05:55:58,192 --> 05:55:59,960
WITH THIS INFORMATION OF MUSCLE

8427
05:55:59,960 --> 05:56:01,929
TISSUE THERE IN A LARGE ANIMAL

8428
05:56:01,929 --> 05:56:05,432
MODEL THAT WILL NOT RESOLVE ON

8429
05:56:05,432 --> 05:56:07,401
ITS OWN.

8430
05:56:07,401 --> 05:56:08,736
NEXT SEVERAL YEARS LOOKING AT

8431
05:56:08,736 --> 05:56:10,271
RELEASE CRITERIA, MAKING SURE WE

8432
05:56:10,271 --> 05:56:12,540
HAD THE RIGHT CELLS, HAVING THE

8433
05:56:12,540 --> 05:56:16,043
RIGHT CELL, THE SAME CELL TYPE

8434
05:56:16,043 --> 05:56:16,810
EVERY TIME.

8435
05:56:16,810 --> 05:56:19,980
THIS IS PART OF OUR STUDY WE HAD

8436
05:56:19,980 --> 05:56:24,618
TWO PATIENTS THAT HAD DEFICIENT

8437
05:56:24,618 --> 05:56:31,825
BLADDER, 7 AND 8, FIRST HAD

8438
05:56:31,825 --> 05:56:32,593
TYPICAL STRESS URINARY

8439
05:56:32,593 --> 05:56:33,360
INCONTINENCE, SHOWING SUCCESS

8440
05:56:33,360 --> 05:56:33,928
WITH THESE PATIENTS.

8441
05:56:33,928 --> 05:56:38,065
ONE OF THE CHALLENGES WAS THAT

8442
05:56:38,065 --> 05:56:38,766
IT'S A VERY EXPENSIVE

8443
05:56:38,766 --> 05:56:39,700
TECHNOLOGY.

8444
05:56:39,700 --> 05:56:41,535
YOU HAVE TO GO THROUGH A LOT OF

8445
05:56:41,535 --> 05:56:42,670
EXPENSES TO GET THIS TECHNOLOGY

8446
05:56:42,670 --> 05:56:43,003
OUT.

8447
05:56:43,003 --> 05:56:45,272
AND THERE ARE OTHER ALTERNATIVES

8448
05:56:45,272 --> 05:56:48,475
OUT THERE THAT MAY BE, YOU KNOW,

8449
05:56:48,475 --> 05:56:51,178
VERY INEXPENSIVE, MAY NOT BE AS

8450
05:56:51,178 --> 05:56:52,713
GOOD, NOT AS EXPENSIVE, THAT'S

8451
05:56:52,713 --> 05:56:55,583
WHEN WE START LOOKING AT PROOF

8452
05:56:55,583 --> 05:56:57,551
OF -- AT, YOU KNOW, JUST DOING

8453
05:56:57,551 --> 05:56:59,520
THIS AT THE PATIENT'S BEDSIDE.

8454
05:56:59,520 --> 05:57:03,991
WE TAKE THE BIOPSY FROM BEDSIDE,

8455
05:57:03,991 --> 05:57:05,125
PROCESS CELLS RIGHT THERE,

8456
05:57:05,125 --> 05:57:07,394
INJECT CELLS WHERE YOU NEED

8457
05:57:07,394 --> 05:57:08,062
THEM, TAKING THEM WHERE THERE'S

8458
05:57:08,062 --> 05:57:10,130
PLENTY OF TISSUE AND PUTTING

8459
05:57:10,130 --> 05:57:12,099
THEM IN OTHER AREAS.

8460
05:57:12,099 --> 05:57:13,500
WE'VE DONE THEM FOR ROTATOR CUFF

8461
05:57:13,500 --> 05:57:14,068
INJURY.

8462
05:57:14,068 --> 05:57:15,836
IF YOU HAVE A ROTATOR CUFF

8463
05:57:15,836 --> 05:57:17,838
INJURY, YOU HAVE A LOT OF MUSCLE

8464
05:57:17,838 --> 05:57:19,974
WEAKNESS, EVEN AT THE TIME OF

8465
05:57:19,974 --> 05:57:22,610
REPAIR BECAUSE THE PATIENT'S

8466
05:57:22,610 --> 05:57:25,980
ALREADY LOST THAT MUSCLE TISSUE,

8467
05:57:25,980 --> 05:57:31,852
CONVERTED TO FAT, INCREASED

8468
05:57:31,852 --> 05:57:34,188
MUSCLE FORMATION, DECREASED FAT

8469
05:57:34,188 --> 05:57:36,390
INFILTRATION AT THE SURGERY, AN

8470
05:57:36,390 --> 05:57:37,358
EXISTING CLINICAL TRIAL AT WAKE

8471
05:57:37,358 --> 05:57:38,025
FOREST.

8472
05:57:38,025 --> 05:57:40,494
AND ANOTHER TRIAL IS FOR FECAL

8473
05:57:40,494 --> 05:57:43,297
INCONTINENCE USING THE SAME

8474
05:57:43,297 --> 05:57:43,897
STRATEGY.

8475
05:57:43,897 --> 05:57:46,033
THIS IS ONE TISSUE, THREE

8476
05:57:46,033 --> 05:57:50,938
APPLICATIONS, SEVERAL PROCESSES

8477
05:57:50,938 --> 05:57:52,039
AND PROCEDURES.

8478
05:57:52,039 --> 05:57:54,141
THIS TOOK DECADES TO DEVELOP, TO

8479
05:57:54,141 --> 05:57:55,743
GET KIDNEY CELLS TO GROW AND

8480
05:57:55,743 --> 05:57:57,745
EXPAND OUTSIDE THE BODY.

8481
05:57:57,745 --> 05:58:01,448
YOU CAN IMAGINE CELLS EXTREMELY

8482
05:58:01,448 --> 05:58:02,549
DIFFICULT, TO HARVEST BECAUSE

8483
05:58:02,549 --> 05:58:04,518
THERE'S SO MANY CELL TYPES IN

8484
05:58:04,518 --> 05:58:06,620
THE KIDNEY.

8485
05:58:06,620 --> 05:58:09,023
WE SPENT YEARS DEVELOPING THIS

8486
05:58:09,023 --> 05:58:10,224
CELL BIOLOGY FOR THESE CELLS,

8487
05:58:10,224 --> 05:58:12,126
THEY COULD NOT BE EXPANDED.

8488
05:58:12,126 --> 05:58:15,396
WITH WE STARTED THIS WORK, THE

8489
05:58:15,396 --> 05:58:17,564
CELLS WERE NOT EXPANDABLE.

8490
05:58:17,564 --> 05:58:18,999
WE HAD TO DO GROWTH FACTOR

8491
05:58:18,999 --> 05:58:21,735
BIOLOGY TO GET THEM TO GROW AND

8492
05:58:21,735 --> 05:58:23,270
EXPAND, PLACED THEM INTO THE

8493
05:58:23,270 --> 05:58:31,679
DEVICES, MADE OUT OF COLLAGEN

8494
05:58:31,679 --> 05:58:36,984
IMPLANTED INTO COWS AND STEER.

8495
05:58:36,984 --> 05:58:40,354
THEY STARTED TO FORM NORMAL

8496
05:58:40,354 --> 05:58:41,689
KIDNEY ISSUE CREATING DILUTE

8497
05:58:41,689 --> 05:58:42,423
URINE.

8498
05:58:42,423 --> 05:58:44,792
THIS IS AN EXAMPLE OF THIS IN

8499
05:58:44,792 --> 05:58:46,293
TERMS OF HISTOLOGICALLY WHAT YOU

8500
05:58:46,293 --> 05:58:56,270
SEE, ON THE TOP LEFT IF WE USE A

8501
05:58:56,270 --> 05:58:57,371
NON-ALLOGENEIC, IT WILL REJECT,

8502
05:58:57,371 --> 05:58:59,540
SAME ON BOTTOM LEFT.

8503
05:58:59,540 --> 05:59:04,244
IF YOU CREATE USING AUTOLOGOUS

8504
05:59:04,244 --> 05:59:08,749
CELLS YOU WITH FORM NORMAL

8505
05:59:08,749 --> 05:59:13,454
PRIMARY AND DISTAL, YOU CAN SEE

8506
05:59:13,454 --> 05:59:17,624
THE DISTAL TUBULE AND SECRETION

8507
05:59:17,624 --> 05:59:21,195
OF DILUTE URINE, AND YOU CAN SEE

8508
05:59:21,195 --> 05:59:22,663
THE UPREGULATION AND

8509
05:59:22,663 --> 05:59:23,764
IDENTIFICATION OF MOLECULAR

8510
05:59:23,764 --> 05:59:26,467
MARKERS AND GENES PRESENT IN

8511
05:59:26,467 --> 05:59:26,900
KIDNEY TISSUE.

8512
05:59:26,900 --> 05:59:36,176
AND SO THAT WAS PUBLISHED IN THE

8513
05:59:36,176 --> 05:59:37,177
JOURNAL NATURE BIOTECHNOLOGY.

8514
05:59:37,177 --> 05:59:38,278
WHERE ARE WE TODAY?

8515
05:59:38,278 --> 05:59:42,349
WE CAN GO TO A 75-YEAR-OLD

8516
05:59:42,349 --> 05:59:43,951
PATIENT OF PATIENT, NEEDLE

8517
05:59:43,951 --> 05:59:45,486
BIOPSY, RETRIEVE A SLIVER OF

8518
05:59:45,486 --> 05:59:48,555
TISSUE WITH SMALL NEEDLE BIOPSY

8519
05:59:48,555 --> 05:59:54,027
AND GET CELLS TO EXPAND OUTSIDE

8520
05:59:54,027 --> 05:59:57,297
IN LARGE QUANTITIES, COLLAGEN

8521
05:59:57,297 --> 05:59:59,800
CARRIER, RESOLUTION OF KIDNEY

8522
05:59:59,800 --> 06:00:00,901
FAILURE, THIS SHOWS

8523
06:00:00,901 --> 06:00:04,071
HISTOLOGICALLY WHAT'S GOING ON,

8524
06:00:04,071 --> 06:00:08,342
YOU SEE TWO NATIVE GLOMERULI,

8525
06:00:08,342 --> 06:00:09,977
NEPHRON UNITS, PLACE A COLLAGEN

8526
06:00:09,977 --> 06:00:11,612
CARRIER WITH NEW KIDNEY CELLS,

8527
06:00:11,612 --> 06:00:13,180
YOU SEE NEW NEPHRON UNITS THAT

8528
06:00:13,180 --> 06:00:15,983
GET FORMED.

8529
06:00:15,983 --> 06:00:16,550
THIS TECHNOLOGY IS ENTERING

8530
06:00:16,550 --> 06:00:22,589
PHASE 3 HUMAN CLINICAL TRIALS,

8531
06:00:22,589 --> 06:00:24,591
NOW PUBLIC HEALTH COMPANY, TAKE

8532
06:00:24,591 --> 06:00:26,226
A KIDNEY BIOPSY, GROW CELLS

8533
06:00:26,226 --> 06:00:27,528
OUTSIDE THE BODY, PUT THEM BACK

8534
06:00:27,528 --> 06:00:29,263
INTO THE KIDNEY.

8535
06:00:29,263 --> 06:00:32,132
THE NICE THING ABOUT THIS

8536
06:00:32,132 --> 06:00:32,800
TECHNOLOGY, PATIENT'S OWN CELLS,

8537
06:00:32,800 --> 06:00:35,102
THEY ARE NOT GOING TO REJECT,

8538
06:00:35,102 --> 06:00:36,036
BASICALLY INK THE CELLS WHERE

8539
06:00:36,036 --> 06:00:38,038
THEY ARE GOING TO TAKE UP

8540
06:00:38,038 --> 06:00:39,907
RESIDENCE AND BE PERMANENT CELLS

8541
06:00:39,907 --> 06:00:41,675
THAT PRODUCE FUNCTION.

8542
06:00:41,675 --> 06:00:43,610
THE OUTCOME OF PHASE 1 AND 2

8543
06:00:43,610 --> 06:00:46,680
CLINICAL TRIALS HAVE BEEN

8544
06:00:46,680 --> 06:00:48,248
PUBLISHED SHOWING DELAY

8545
06:00:48,248 --> 06:00:51,285
BASICALLY PREVENTING PATIENTS 

8546
06:00:51,285 --> 06:00:55,556
FROM GETTING TO DIALYSIS.

8547
06:00:55,556 --> 06:00:58,025
WE'VE USED A LOT OF STRATEGIES

8548
06:00:58,025 --> 06:00:58,692
USING BIOMATERIALS.

8549
06:00:58,692 --> 06:01:01,328
SO HERE IS AN EXAMPLE OF THAT.

8550
06:01:01,328 --> 06:01:10,304
WE TAKE A SMALL BIOPSY FOR

8551
06:01:10,304 --> 06:01:11,638
REPAIR, EXPAND CELLS OUTSIDE THE

8552
06:01:11,638 --> 06:01:17,244
BODY, TAKE A SCAFFOLD THAT WE

8553
06:01:17,244 --> 06:01:18,979
TUBULARRIZE, COAT THE OUTSIDE,

8554
06:01:18,979 --> 06:01:21,481
THE INSIDE, PUT IT RIGHT BACK

8555
06:01:21,481 --> 06:01:22,616
INTO THE BODY, THE PROCESS TAKES

8556
06:01:22,616 --> 06:01:24,785
FOUR TO SIX WEEKS.

8557
06:01:24,785 --> 06:01:27,621
WE BASICALLY USE MATERIALS, WE

8558
06:01:27,621 --> 06:01:30,924
HAVE ABOUT 60 BIOMATERIALS THAT

8559
06:01:30,924 --> 06:01:34,061
WE MIX AND MATCH TO CREATE THE

8560
06:01:34,061 --> 06:01:36,063
STRUCTURE, REVERSE ENGINEERING.

8561
06:01:36,063 --> 06:01:42,736
NORMAL TISSUE SAMPLES FROM HUMAN

8562
06:01:42,736 --> 06:01:43,403
PATIENTS, REPLICATE PROPERTIES

8563
06:01:43,403 --> 06:01:45,172
TO CREATE THE BIOMATERIALS THAT

8564
06:01:45,172 --> 06:01:48,675
WE NEED, AND WILL BE BEST FOR

8565
06:01:48,675 --> 06:01:49,643
THESE TISSUES.

8566
06:01:49,643 --> 06:01:51,945
OBVIOUSLY MATERIAL FOR BLOOD

8567
06:01:51,945 --> 06:01:52,713
VESSELS WILL BE DIFFERENT THAN

8568
06:01:52,713 --> 06:01:54,481
FOR A PIECE OF BONE.

8569
06:01:54,481 --> 06:02:05,025
FOR  THE URETHRA, A MAJOR INJURY

8570
06:02:07,094 --> 06:02:17,537
WITH MOTOR VEHICLE ACCIDENT, 

8571
06:02:23,410 --> 06:02:24,845
SCAFFOLD, THE URETHRAL, AND SIX

8572
06:02:24,845 --> 06:02:26,613
YEAR FOLLOW-UP, THE PILOT SERIES

8573
06:02:26,613 --> 06:02:30,250
WITH INJURIES ON TOP, EARLIEST

8574
06:02:30,250 --> 06:02:35,822
POST-OP THREE MONTHS LATER,

8575
06:02:35,822 --> 06:02:38,625
LATER SIX YEARS LATER SHOWING

8576
06:02:38,625 --> 06:02:44,464
GOOD FUNCTION JUST  DID --

8577
06:02:44,464 --> 06:02:46,533
FUNCTIONALITY LONG TERM.

8578
06:02:46,533 --> 06:02:48,735
AND WITH BLOOD VESSELS, WE

8579
06:02:48,735 --> 06:02:52,406
EXPAND AND CREATE THESE TRILAYER

8580
06:02:52,406 --> 06:02:52,839
STRUCTURES.

8581
06:02:52,839 --> 06:02:55,909
THIS IS ACTUALLY SOME OF THE

8582
06:02:55,909 --> 06:02:58,812
VERY EARLY BIOREACTORS IN THE

8583
06:02:58,812 --> 06:03:00,547
EARLY 1990s, CREATED TUBULAR

8584
06:03:00,547 --> 06:03:02,382
STRUCTURES THEY WOULD COLLAPSE.

8585
06:03:02,382 --> 06:03:09,923
WE WENT TO OUR BIOMECHANICAL 

8586
06:03:09,923 --> 06:03:11,391
COLLEAGUES AT CHILDREN'S

8587
06:03:11,391 --> 06:03:12,259
HOSPITAL BOSTON, WE NEEDED

8588
06:03:12,259 --> 06:03:15,495
SOMETHING TO KEEP THESE PUMPING.

8589
06:03:15,495 --> 06:03:18,065
THIS IS AN EARLY BIOREACTOR YOU

8590
06:03:18,065 --> 06:03:20,100
SEE FOR BLOOD VESSELS.

8591
06:03:20,100 --> 06:03:22,736
THEY CONDITIONED BLOOD VESSEL

8592
06:03:22,736 --> 06:03:25,806
BEFORE IMPLANTED, CAROTID ARTERY

8593
06:03:25,806 --> 06:03:26,840
IMPLANTED USING THESE

8594
06:03:26,840 --> 06:03:27,140
STRATEGIES.

8595
06:03:27,140 --> 06:03:28,442
SO MUCH WORK HAS BEEN DONE IN

8596
06:03:28,442 --> 06:03:31,044
THIS AREA OF BLOOD VESSELS,

8597
06:03:31,044 --> 06:03:33,347
CHRIS BREWER IS HERE WHO I'M

8598
06:03:33,347 --> 06:03:37,150
SURE IS PRESENTING HIS WORK WITH

8599
06:03:37,150 --> 06:03:38,418
SHALL HEART VALVES, A LOT OF

8600
06:03:38,418 --> 06:03:40,253
THINGS GOING ON WITH

8601
06:03:40,253 --> 06:03:41,121
TISSUE-SPECIFIC CELLS.

8602
06:03:41,121 --> 06:03:44,291
WE'VE TALKED ABOUT SOME OF THESE

8603
06:03:44,291 --> 06:03:44,591
STRUCTURES.

8604
06:03:44,591 --> 06:03:46,460
FLAT STRUCTURES LIKE SKIN ARE

8605
06:03:46,460 --> 06:03:48,695
THE LEAST COMPLEX.

8606
06:03:48,695 --> 06:03:50,664
TUBULAR STRUCTURES LIKE BLOOD

8607
06:03:50,664 --> 06:03:57,004
VESSELS SECOND LEVEL OF

8608
06:03:57,004 --> 06:03:57,304
COMPLEXITY.

8609
06:03:57,304 --> 06:04:00,941
HOLLOW NON-TUBULAR ORGANS, CELLS

8610
06:04:00,941 --> 06:04:07,381
ARE MORE COMPLEX, ARCHITECTURE

8611
06:04:07,381 --> 06:04:09,016
MORE COMPLEX, COULD NOT GET THEM

8612
06:04:09,016 --> 06:04:10,984
TO GROW OUTSIDE THE BOTH, HAD TO

8613
06:04:10,984 --> 06:04:11,952
GO TO GROWTH FACTOR BIOLOGY.

8614
06:04:11,952 --> 06:04:14,721
THIS IS WHAT LED US TO BE ABLE

8615
06:04:14,721 --> 06:04:17,024
TO EXPAND CELLS, AGAIN MATCH

8616
06:04:17,024 --> 06:04:19,559
WITH BIOMATERIALS, FIRST IMPLANT

8617
06:04:19,559 --> 06:04:23,463
CELLS IN A THYMIC MICE.

8618
06:04:23,463 --> 06:04:24,865
ONCE WE SEE IT RECONSTITUTES IN

8619
06:04:24,865 --> 06:04:28,635
THE BACK OF A MOUSE WE GO TO

8620
06:04:28,635 --> 06:04:29,403
LARGER ANIMAL MODEL.

8621
06:04:29,403 --> 06:04:31,705
WE NEVER DO A SUBSTITUTION IN

8622
06:04:31,705 --> 06:04:32,906
RODENT MODEL BECAUSE EVERYTHING

8623
06:04:32,906 --> 06:04:33,573
WE GENERATES.

8624
06:04:33,573 --> 06:04:36,843
EVEN IN A RABBIT YOU HAVE TO GO

8625
06:04:36,843 --> 06:04:38,311
TO CRITICAL DEFECT, EVEN PARTIAL

8626
06:04:38,311 --> 06:04:38,779
REPLACEMENT WON'T DO.

8627
06:04:38,779 --> 06:04:40,814
YOU HAVE TO GO TO FULL

8628
06:04:40,814 --> 06:04:42,282
REPLACEMENT TO SHOW THAT THE

8629
06:04:42,282 --> 06:04:42,883
TECHNOLOGY WILL WORK.

8630
06:04:42,883 --> 06:04:44,418
ANYTHING UP TO HALF A SENT

8631
06:04:44,418 --> 06:04:45,886
MEETER FROM THE EDGE WILL

8632
06:04:45,886 --> 06:04:48,155
REGENERATE ON ITS OWN.

8633
06:04:48,155 --> 06:04:49,122
IN RODENTS THAT'S FAIRLY EASY TO

8634
06:04:49,122 --> 06:04:49,623
DO.

8635
06:04:49,623 --> 06:04:51,625
THIS IS A RABBIT MODEL.

8636
06:04:51,625 --> 06:04:54,394
WE TOOK THE ORGAN OUT.

8637
06:04:54,394 --> 06:05:01,301
WE THEN IMPLANTED NEW ORGAN.

8638
06:05:01,301 --> 06:05:09,142
X-RAYS SHOW BEFORE,  DON'T SEED

8639
06:05:09,142 --> 06:05:10,110
IT WON'T WORK.

8640
06:05:10,110 --> 06:05:12,012
BY ONE MONTH IT'S NOT YET

8641
06:05:12,012 --> 06:05:12,279
COMPLETE.

8642
06:05:12,279 --> 06:05:15,782
YOU CAN SEE HERE ON THE TOP LEFT

8643
06:05:15,782 --> 06:05:19,419
THAT YOU CAN STILL SEE THROUGH

8644
06:05:19,419 --> 06:05:21,188
THE THIN MUSCLE LAYER, YOU CAN

8645
06:05:21,188 --> 06:05:23,156
RIGHT THROUGH TO THE SCAFFOLD

8646
06:05:23,156 --> 06:05:23,557
ITSELF.

8647
06:05:23,557 --> 06:05:24,691
IT KEEPS REGENERATING IN THE

8648
06:05:24,691 --> 06:05:26,193
BODY, BY SIX MONTHS FULLY

8649
06:05:26,193 --> 06:05:28,495
FORMED, BY THEN THE SCAFFOLD IS

8650
06:05:28,495 --> 06:05:30,130
DEGRADED, AND THEN THAT'S WHEN

8651
06:05:30,130 --> 06:05:32,065
YOU ACTUALLY CAN START TO

8652
06:05:32,065 --> 06:05:34,401
ANALYZE THESE LOOKING AT THE

8653
06:05:34,401 --> 06:05:43,944
PHENOTYPES,  NORMAL BY SIX

8654
06:05:43,944 --> 06:05:46,746
MONTHS, MOLECULAR MARKERS AND

8655
06:05:46,746 --> 06:05:47,681
GENES ALSO APPROXIMATING NORMAL

8656
06:05:47,681 --> 06:05:54,020
BY SIX MONTHS.

8657
06:05:54,020 --> 06:05:57,424
MATRICES DEGRADED BY SIX MONTHS.

8658
06:05:57,424 --> 06:05:59,392
YOU'RE SEEING EXTRACELLULAR

8659
06:05:59,392 --> 06:06:00,494
MATRIX, AT SCAFFOLD DEGRADES THE

8660
06:06:00,494 --> 06:06:01,928
CELLS DO WHAT THEY DO IN YOUR

8661
06:06:01,928 --> 06:06:06,399
BODY, LAY DOWN ITS OWN MATRIX.

8662
06:06:06,399 --> 06:06:09,269
YOU CAN SEE THE COLLAGEN ONE,

8663
06:06:09,269 --> 06:06:10,570
TWO, THREE, COLLAGEN DISTRIBUTES

8664
06:06:10,570 --> 06:06:14,975
THAT OF A NORMAL ORGAN.

8665
06:06:14,975 --> 06:06:15,809
BIOMECHANICAL TESTING,

8666
06:06:15,809 --> 06:06:17,144
APPROXIMATES NORMAL BY SIX

8667
06:06:17,144 --> 06:06:19,012
MONTHS.

8668
06:06:19,012 --> 06:06:21,515
WE'LL LOOK AT INNERVATION,

8669
06:06:21,515 --> 06:06:23,183
APPROXIMATES NORMAL ORGAN BY SIX

8670
06:06:23,183 --> 06:06:24,818
MONTHS.

8671
06:06:24,818 --> 06:06:27,120
CRITICALLY IMPORTANT YOU TEST

8672
06:06:27,120 --> 06:06:29,189
INNERVATION IN VITRO.

8673
06:06:29,189 --> 06:06:31,925
WE TAKE SAMPLES AND DO STUDIES

8674
06:06:31,925 --> 06:06:33,260
TO SHOW INNERVATION IS COMING

8675
06:06:33,260 --> 06:06:37,831
FROM THE TISSUE YOU ARE

8676
06:06:37,831 --> 06:06:39,766
ENGINEERED NOT THE PERIPHERY,

8677
06:06:39,766 --> 06:06:45,572
TAKING TO PATIENTS, AN MRI, A

8678
06:06:45,572 --> 06:06:46,473
PATIENT WITH VAGINAL AGENESIS,

8679
06:06:46,473 --> 06:06:51,144
YOU SEE THE RECTUM ON THE RIGHT,

8680
06:06:51,144 --> 06:06:56,049
BLADDER ON LEFT, AND IT'S A

8681
06:06:56,049 --> 06:06:56,983
RUDIMENT TEMPORARY STRUCTURE,

8682
06:06:56,983 --> 06:06:58,485
TAKE A BIOPSY, EXPAND CELLS

8683
06:06:58,485 --> 06:07:03,423
OUTSIDE THE BODY, CREATE THE

8684
06:07:03,423 --> 06:07:05,892
CONSTRUCT, THE TEENAGE PATIENT

8685
06:07:05,892 --> 06:07:06,826
HAD THE ENGINEERED IMPLANT ONE

8686
06:07:06,826 --> 06:07:08,328
YEAR LATER, THAT'S WHAT YOU SEE

8687
06:07:08,328 --> 06:07:09,996
RIGHT THERE.

8688
06:07:09,996 --> 06:07:10,997
WE FOLLOWED THESE PATIENTS FOR

8689
06:07:10,997 --> 06:07:12,098
EIGHT YEARS.

8690
06:07:12,098 --> 06:07:15,569
WE FOLLOWED THESE PATIENTS WITH

8691
06:07:15,569 --> 06:07:18,538
YEARLY ENDOSCOPY AND BIOPSY AND

8692
06:07:18,538 --> 06:07:20,040
MOLECULAR TESTING, YEARLY

8693
06:07:20,040 --> 06:07:22,275
MRIs, AND YEARLY FUNCTIONAL

8694
06:07:22,275 --> 06:07:23,276
TESTING TO SHOW ORGANS CONTINUE

8695
06:07:23,276 --> 06:07:26,112
TO DO WELL OVER TIME.

8696
06:07:26,112 --> 06:07:28,615
AND SO FUNCTIONALLY THEY DID

8697
06:07:28,615 --> 06:07:30,584
VERY WELL, AND WE PUBLISHED THAT

8698
06:07:30,584 --> 06:07:32,886
IN " THE LANCET," MANY PEOPLE

8699
06:07:32,886 --> 06:07:35,889
ASK WHY DID YOU WAIT EIGHT YEARS

8700
06:07:35,889 --> 06:07:37,791
FOLLOW UP?

8701
06:07:37,791 --> 06:07:39,793
IF YOU'RE DOING TYPICAL

8702
06:07:39,793 --> 06:07:41,328
RECONSTRUCTIVE SURGERY USING

8703
06:07:41,328 --> 06:07:42,963
BOWEL OR SKIN, YOU SEE FAILURE

8704
06:07:42,963 --> 06:07:44,497
UP TO YEAR FIVE.

8705
06:07:44,497 --> 06:07:46,066
WE WANTED TO MAKE SURE WE WERE

8706
06:07:46,066 --> 06:07:47,667
WAY PAST THAT TIME LINE TO MAKE

8707
06:07:47,667 --> 06:07:50,170
SURE THERE WERE NO CHALLENGES.

8708
06:07:50,170 --> 06:07:54,207
WE'RE CONTINUING THIS WORK,

8709
06:07:54,207 --> 06:07:55,075
IMPLANTED ENGINEERED VAGINAL

8710
06:07:55,075 --> 06:07:56,743
ORGANS THROUGH SIX WEEKS AGO AT

8711
06:07:56,743 --> 06:07:57,944
WAKE FOREST.

8712
06:07:57,944 --> 06:08:00,146
THE FIRST ORGAN WE IMPLANTED WAS

8713
06:08:00,146 --> 06:08:02,415
A BLADDER BUT I'M SHOWING ORDER

8714
06:08:02,415 --> 06:08:04,117
OF COMPLEXITY.

8715
06:08:04,117 --> 06:08:05,952
WITH BLADDER, THE SAME STRATEGY,

8716
06:08:05,952 --> 06:08:08,888
SMALL BIOPSY OF THE BLADDER,

8717
06:08:08,888 --> 06:08:12,425
EXPAND CELLS OUTSIDE THE BODY,

8718
06:08:12,425 --> 06:08:14,127
CREATE CONSTRUCT, SEED WITH

8719
06:08:14,127 --> 06:08:15,595
EPITHELIAL CELLS, OUTSIDE WITH

8720
06:08:15,595 --> 06:08:17,564
MUSCLE CELLS, PLACE IN

8721
06:08:17,564 --> 06:08:19,766
BIOREACTOR, BACK INTO THE

8722
06:08:19,766 --> 06:08:22,335
PATIENT.

8723
06:08:22,335 --> 06:08:24,638
PUBLISHED PRE-CLINICAL WORK IN

8724
06:08:24,638 --> 06:08:28,174
NATURE BIOTECHNOLOGY, IF WE HAD

8725
06:08:28,174 --> 06:08:29,476
KNOWN WE WOULD HAVE NOT STARTED

8726
06:08:29,476 --> 06:08:31,978
WITH LEVEL 3 BUT IT HELPED US

8727
06:08:31,978 --> 06:08:36,049
DEVELOP THE OTHER  ORGANS.

8728
06:08:36,049 --> 06:08:38,285
THESE WERE PATIENTS WITH END

8729
06:08:38,285 --> 06:08:40,186
STAGE BLADDER DISEASE AND SO

8730
06:08:40,186 --> 06:08:41,288
THEY RECEIVED THEIR TREATMENT,

8731
06:08:41,288 --> 06:08:43,657
AND THIS IS ACTUALLY THE STUDY

8732
06:08:43,657 --> 06:08:45,692
THAT GAVE US THE IDEA TO DO

8733
06:08:45,692 --> 06:08:46,059
IMAGING.

8734
06:08:46,059 --> 06:08:49,663
THIS IS A LONG TIME AGO, WE DID

8735
06:08:49,663 --> 06:08:51,998
NOT HAVE THE ABILITY TO

8736
06:08:51,998 --> 06:08:53,300
DETERMINE WHAT SIZE OR CONSTRUCT

8737
06:08:53,300 --> 06:08:55,468
WE SHOULD BE SO THEY WOULD FIT

8738
06:08:55,468 --> 06:08:59,572
INSIDE THE PELVIC CAVITY.

8739
06:08:59,572 --> 06:09:07,647
WE WENT TO OUR COLLEAGUES, 

8740
06:09:07,647 --> 06:09:09,616
PHYSICISTS IN RADIOLOGY, ALSO AT

8741
06:09:09,616 --> 06:09:12,585
BOSTON, TO RECONSTRUCT AND THE

8742
06:09:12,585 --> 06:09:13,687
PELVIC CAVITY, ENGINEERS

8743
06:09:13,687 --> 06:09:16,690
CONSTRUCTS SPECIFICALLY FOR EACH

8744
06:09:16,690 --> 06:09:17,257
PATIENT.

8745
06:09:17,257 --> 06:09:18,758
WE SIZE THEM BASED ON WHAT WE

8746
06:09:18,758 --> 06:09:20,660
THOUGHT THE PELVIC CAVITY WOULD

8747
06:09:20,660 --> 06:09:21,695
ACCOMMODATE.

8748
06:09:21,695 --> 06:09:23,897
THIS IS ENGINEERED BLADDER

8749
06:09:23,897 --> 06:09:25,465
IMPLANTED, AAP AND LATERAL VIEW,

8750
06:09:25,465 --> 06:09:27,567
SCAFFOLD ON TOP, ON THE BOTTOM

8751
06:09:27,567 --> 06:09:30,837
LEFT YOU SEE THE ENGINEERED

8752
06:09:30,837 --> 06:09:35,241
BLADDER BEING IMPLANTED WITH

8753
06:09:35,241 --> 06:09:36,676
OMENTUM, SHOWING THE PATIENT

8754
06:09:36,676 --> 06:09:38,611
BEFORE AND AFTER SURGERY A YEAR

8755
06:09:38,611 --> 06:09:40,046
AFTER SURGERY.

8756
06:09:40,046 --> 06:09:43,650
MOST IMPORTANT WAS KEEPING THOSE

8757
06:09:43,650 --> 06:09:44,751
PRESSURES DOWN.

8758
06:09:44,751 --> 06:09:45,719
THERE'S ACTUALLY A PAPER

8759
06:09:45,719 --> 06:09:49,155
PRESENTED BY DR. ALLEN REDDICK,

8760
06:09:49,155 --> 06:09:50,357
SURGEON IN CHIEF CHILDREN'S

8761
06:09:50,357 --> 06:09:55,028
HOSPITAL IN  HARVARD MEDICAL

8762
06:09:55,028 --> 06:09:58,732
SCHOOL, AS CHILDREN GREW 

8763
06:09:58,732 --> 06:10:04,070
GLADDERS CREW -- BLADDERS GREW

8764
06:10:04,070 --> 06:10:07,640
WITH THE PATIENTS.

8765
06:10:07,640 --> 06:10:14,614
YOU NEED  NEED TO CYCLE.

8766
06:10:14,614 --> 06:10:18,785
THIS WAS OUR ORIGINAL PAPER IN "

8767
06:10:18,785 --> 06:10:21,154
THE LANCET," AND IT'S TAKEN A

8768
06:10:21,154 --> 06:10:23,723
LONG TIME BECAUSE WE TRANSFERRED

8769
06:10:23,723 --> 06:10:27,060
THIS TO A COMPANY, AND THEN THE

8770
06:10:27,060 --> 06:10:29,629
COMPANIES END UP SPENDING

8771
06:10:29,629 --> 06:10:32,866
INORDINATE AMOUNTS OF MORE  --

8772
06:10:32,866 --> 06:10:34,734
AMOUNTS OF MONEY TO GET IT OUT

8773
06:10:34,734 --> 06:10:36,035
THE DOOR.

8774
06:10:36,035 --> 06:10:38,104
WHEN DO YOU REACH TECHNOLOGY TO

8775
06:10:38,104 --> 06:10:38,371
INDUSTRY?

8776
06:10:38,371 --> 06:10:39,439
ANOTHER DISCUSSION.

8777
06:10:39,439 --> 06:10:41,841
THIS IS ACTUALLY SHOWING THE

8778
06:10:41,841 --> 06:10:43,510
FORMATION OF SOLID ORGANS.

8779
06:10:43,510 --> 06:10:46,913
BY FAR THE THOSE COMPLEX ORGANS

8780
06:10:46,913 --> 06:10:57,457
ARE SOLID ORGANS, THE  THALL USS

8781
06:11:04,130 --> 06:11:04,497
IS VASCULAR.

8782
06:11:04,497 --> 06:11:08,334
THIS GAVE YOU WILLS THE IDEA

8783
06:11:08,334 --> 06:11:14,140
USING SOLID ORBANS, IN  -- IN

8784
06:11:14,140 --> 06:11:15,642
THE ORGANS.

8785
06:11:15,642 --> 06:11:18,077
WE HAD THE IDEA, WHY DON'T WE

8786
06:11:18,077 --> 06:11:20,980
TAKE A DONOR SOLID ORGAN, MILD

8787
06:11:20,980 --> 06:11:29,823
DETERGENTS, WASH CELLS AND REUSE

8788
06:11:29,823 --> 06:11:32,058
THAT STRUCTURE FOR THE ORGAN.

8789
06:11:32,058 --> 06:11:34,160
THIS IS A TOTAL REPLACEMENT

8790
06:11:34,160 --> 06:11:37,797
SHOWING ON THE TOP LEFT THE

8791
06:11:37,797 --> 06:11:42,202
NORMAL CONTROL, AND TOP RIGHT

8792
06:11:42,202 --> 06:11:44,637
THE ENGINEERED.

8793
06:11:44,637 --> 06:11:45,805
THIS SHOWS VASCULARITY, CONTROLS

8794
06:11:45,805 --> 06:11:49,309
DID NOT DO WELL.

8795
06:11:49,309 --> 06:11:52,345
BY SIX MONTHS PRESSURES WERE

8796
06:11:52,345 --> 06:11:53,780
SIGNIFICANT, WE WERE ABLE TO

8797
06:11:53,780 --> 06:11:57,283
MATE THESE ANIMALS WITH FEMALE

8798
06:11:57,283 --> 06:11:59,586
PARTNERS, WERE ABLE TO SHOW

8799
06:11:59,586 --> 06:12:02,856
PREGNANCY RATES THROUGH THESE

8800
06:12:02,856 --> 06:12:03,823
ENGINEERED ORGANS, AND THIS IS

8801
06:12:03,823 --> 06:12:06,626
NOW APPROVED BY FDA TO PROCEED

8802
06:12:06,626 --> 06:12:09,829
TO PHASE 1 HUMAN CLINICAL

8803
06:12:09,829 --> 06:12:10,063
TRIALS.

8804
06:12:10,063 --> 06:12:12,265
BASICALLY THIS IS WORK FUNDED BY

8805
06:12:12,265 --> 06:12:15,668
THE DoD DUE TO IMPROVISED

8806
06:12:15,668 --> 06:12:17,070
EXPLOSIVE DEVICES.

8807
06:12:17,070 --> 06:12:27,280
THIS SOLID ORGAN STRATEGY WE 

8808
06:12:27,280 --> 06:12:32,719
STARTED WITH THE PHALLUS WE

8809
06:12:32,719 --> 06:12:39,192
TRANS TRANSFERRED TO THE

8810
06:12:39,192 --> 06:12:39,425
DELIVER.

8811
06:12:39,425 --> 06:12:42,262
IT WORKED WITH SMALL MODELS LIKE

8812
06:12:42,262 --> 06:12:42,495
FERRETS.

8813
06:12:42,495 --> 06:12:44,964
IT ONLY WORKS WELL FOR THE LARGE

8814
06:12:44,964 --> 06:12:46,399
AREA WHERE THE CAPILLARIES ARE

8815
06:12:46,399 --> 06:12:46,566
AT.

8816
06:12:46,566 --> 06:12:48,468
IF YOU GO TO THE END CAPILLARIES

8817
06:12:48,468 --> 06:12:53,172
THEY START TO CLOT OFF.

8818
06:12:53,172 --> 06:12:56,609
AND THEN A SITE FOR THROMBI.

8819
06:12:56,609 --> 06:12:59,112
WE'RE ABLE TO REPRODUCE ALL THE

8820
06:12:59,112 --> 06:13:02,749
ELEMENTS, IN TERMS OF HEPATOCYTE

8821
06:13:02,749 --> 06:13:05,218
DIFFERENTIATION FROM HUMAN FETAL

8822
06:13:05,218 --> 06:13:08,421
LIVER, THEY DO SECRETE ALBUMIN

8823
06:13:08,421 --> 06:13:10,857
AND UREA, YOU'RE STILL NOT READY

8824
06:13:10,857 --> 06:13:13,459
FOR PRIME TIME IN HUMANS, THE

8825
06:13:13,459 --> 06:13:15,428
SAME FOR KIDNEYS AND OTHER

8826
06:13:15,428 --> 06:13:16,195
ORGANS.

8827
06:13:16,195 --> 06:13:20,366
IT'S GOOD FOR THE PHALLUS

8828
06:13:20,366 --> 06:13:23,937
BECAUSE IT'S SPONGY TISSUE

8829
06:13:23,937 --> 06:13:28,474
WITHOUT END CAPILLARY.

8830
06:13:28,474 --> 06:13:30,376
TECHNOLOGY TWO DECADES AGO WE

8831
06:13:30,376 --> 06:13:32,579
LOOKED AT PRINTING THESE

8832
06:13:32,579 --> 06:13:33,379
STRUCTURES, CREATING PRINTERS TO

8833
06:13:33,379 --> 06:13:35,214
DO THIS IN A BETTER WAY.

8834
06:13:35,214 --> 06:13:37,383
THIS WAS A 14-YEAR PERIOD TO

8835
06:13:37,383 --> 06:13:39,519
CREATE PRINTERS WHERE THEY HAVE

8836
06:13:39,519 --> 06:13:46,826
FIVE FEATURES, NUMBER ONE SMALL

8837
06:13:46,826 --> 06:13:49,028
NOZZLES, RISK WE CAN DEPOSIT

8838
06:13:49,028 --> 06:13:49,762
CELLS WHERE NEEDED, THAT'S

8839
06:13:49,762 --> 06:13:50,630
FEATURE 2.

8840
06:13:50,630 --> 06:13:58,438
THAT'S VERY IMPORTANT TO DO THAT

8841
06:13:58,438 --> 06:13:59,105
REPRODUCIBLE.

8842
06:13:59,105 --> 06:14:01,307
NUMBER 3 THEY RETAIN INTEGRITY,

8843
06:14:01,307 --> 06:14:05,178
THEY DON'T SPLATTER.

8844
06:14:05,178 --> 06:14:06,646
NUMBER 4 CREATE MICROCHANNELS,

8845
06:14:06,646 --> 06:14:07,847
TO MAKE SURE THE NUTRITION

8846
06:14:07,847 --> 06:14:10,683
IMPOSE TO CENTRAL PORTION OF

8847
06:14:10,683 --> 06:14:11,017
CONSTRUCT.

8848
06:14:11,017 --> 06:14:14,087
AND FEATURE NUMBER 5 IS WE USE

8849
06:14:14,087 --> 06:14:18,291
CURRENTLY AVAILABLE 3D IMAGING

8850
06:14:18,291 --> 06:14:19,292
SYSTEMS LIKE TERRA RECON

8851
06:14:19,292 --> 06:14:20,660
AVAILABLE IN EVERY MAJOR

8852
06:14:20,660 --> 06:14:28,201
HOSPITAL, CREATE OUR  SOFTWARE

8853
06:14:28,201 --> 06:14:30,236
PROGRAM TO PRINT STRUCTURES

8854
06:14:30,236 --> 06:14:32,038
SPECIFICALLY FOR THIS SPECIFIC

8855
06:14:32,038 --> 06:14:32,905
DEFECT.

8856
06:14:32,905 --> 06:14:36,309
THAT WAS ALSO HIGHLIGHTED IN

8857
06:14:36,309 --> 06:14:38,311
NATURE BIOTECHNOLOGY IN 2016.

8858
06:14:38,311 --> 06:14:40,013
A RECENT PAPER JUST COME OUT

8859
06:14:40,013 --> 06:14:41,047
THREE WEEKS AGO.

8860
06:14:41,047 --> 06:14:43,383
THERE'S A PAPER WHERE WE'RE ABLE

8861
06:14:43,383 --> 06:14:47,353
TO PRINT, PUBLISHED IN SCIENCE,

8862
06:14:47,353 --> 06:14:48,254
TRANSLATIONAL MEDICINE, PRINT

8863
06:14:48,254 --> 06:14:50,323
FULL THICKNESS SKIN, SHOWING CAN

8864
06:14:50,323 --> 06:14:51,658
YOU IN FACT CREATE FULL

8865
06:14:51,658 --> 06:14:54,927
THICKNESS SKIN WITH ALL SIX

8866
06:14:54,927 --> 06:14:56,629
LAYERS WITH ALL THREE LAYERS,

8867
06:14:56,629 --> 06:14:58,564
ALL SIX CELL TIMES.

8868
06:14:58,564 --> 06:14:59,732
THIS JUST GOT PUBLISHED A FEW

8869
06:14:59,732 --> 06:15:05,204
WEEKS AGO.

8870
06:15:05,204 --> 06:15:06,239
THIS PRINTER, THERE'S A

8871
06:15:06,239 --> 06:15:11,678
CHALLENGE NASA PUT OUT TO CREATE

8872
06:15:11,678 --> 06:15:13,246
SOLID TISSUE TO REMAIN ALIVE

8873
06:15:13,246 --> 06:15:15,181
OUTSIDE THE BODY FOR ONE MONTH,

8874
06:15:15,181 --> 06:15:16,182
CRITICAL FOR NASA.

8875
06:15:16,182 --> 06:15:17,950
IN TERMS OF SPACE TRAVEL, YOU

8876
06:15:17,950 --> 06:15:22,822
THIS WAS A CHALLENGE FOR US,

8877
06:15:22,822 --> 06:15:23,823
ANYTIME WE ENGINEER TISSUE WE

8878
06:15:23,823 --> 06:15:27,260
PUT IT BACK INTO THE PATIENT.

8879
06:15:27,260 --> 06:15:28,528
HERE WE WERE ASKED TO KEEP IT

8880
06:15:28,528 --> 06:15:30,930
FOR A MONTH AND ALSO SOLID

8881
06:15:30,930 --> 06:15:32,098
TISSUE.

8882
06:15:32,098 --> 06:15:36,803
TWO ENTRIES IN COMPETITION.

8883
06:15:36,803 --> 06:15:39,005
WE ENTERED TWICE, TWO OUT OF 22

8884
06:15:39,005 --> 06:15:40,339
ENTRIES WERE OURS.

8885
06:15:40,339 --> 06:15:42,341
ONE YEAR BEFORE THE CHALLENGE

8886
06:15:42,341 --> 06:15:46,713
WAS OVER, THERE WERE STILL 17

8887
06:15:46,713 --> 06:15:46,979
STANDING.

8888
06:15:46,979 --> 06:15:50,717
ONLY TWO TEAMS MADE IT TO THE

8889
06:15:50,717 --> 06:15:51,317
END.

8890
06:15:51,317 --> 06:15:52,552
THEY NEVER AWARDED THIRD PRIZE

8891
06:15:52,552 --> 06:15:54,520
BECAUSE NO OTHER TIME COULD

8892
06:15:54,520 --> 06:15:55,421
ACHIEVE IT.

8893
06:15:55,421 --> 06:15:58,791
BOTH TEAMS WERE OUR TEAMS AT THE

8894
06:15:58,791 --> 06:15:59,225
INSTITUTE.

8895
06:15:59,225 --> 06:16:01,427
AND THE REASON WE WERE ABLE, WE

8896
06:16:01,427 --> 06:16:03,196
HAD SPENT 14 YEARS DEVELOPING

8897
06:16:03,196 --> 06:16:04,731
THESE PRINTERS THAT REALLY DO

8898
06:16:04,731 --> 06:16:06,766
ALLOW YOU TO HAVE THIS VASCULAR

8899
06:16:06,766 --> 06:16:08,201
NETWORK THAT IS NECESSARY.

8900
06:16:08,201 --> 06:16:11,804
SO JUST IN MAY OF THIS YEAR THE

8901
06:16:11,804 --> 06:16:14,741
ACTION ROCKET WENT UP INTO SPACE

8902
06:16:14,741 --> 06:16:18,511
WITH PRINTED KIDNEY AND LIVER

8903
06:16:18,511 --> 06:16:20,680
STRUCTURES, AND WE HAD FOUR MORE

8904
06:16:20,680 --> 06:16:28,187
MISSIONS FUNDED BY NASA AND THE

8905
06:16:28,187 --> 06:16:29,021
INTERNATIONAL SPACE --

8906
06:16:29,021 --> 06:16:29,689
INTERNATIONAL LABORATORY.

8907
06:16:29,689 --> 06:16:33,793
EVERYTHING IS A USE OF

8908
06:16:33,793 --> 06:16:37,630
ORGAN-SPECIFIC CELLS THAT I'VE

8909
06:16:37,630 --> 06:16:38,030
DESCRIBED.

8910
06:16:38,030 --> 06:16:40,133
WE CAN DIFFERENTIATE INTO

8911
06:16:40,133 --> 06:16:41,000
TISSUE-SPECIFIC CELLS, THAT'S

8912
06:16:41,000 --> 06:16:43,035
ALSO GOOD STRATEGY.

8913
06:16:43,035 --> 06:16:45,004
AND WE PREFER OF COURSE FIRST

8914
06:16:45,004 --> 06:16:45,838
STRATEGY BECAUSE YOU USE

8915
06:16:45,838 --> 06:16:46,806
AUTOLOGOUS CELLS THAT WON'T

8916
06:16:46,806 --> 06:16:48,808
REJECT, THEY KNOW WHAT THEY ARE

8917
06:16:48,808 --> 06:16:51,644
BUT THIS IS A PRACTICAL

8918
06:16:51,644 --> 06:16:52,512
STRATEGY, EXTREMELY USEFUL, JUST

8919
06:16:52,512 --> 06:16:55,648
LET ME SHOW THIS WORK WE JUST

8920
06:16:55,648 --> 06:16:58,351
PUBLISHED ALSO THIS YEAR.

8921
06:16:58,351 --> 06:17:01,821
THIS IS FOR STAGE 4 CARTILAGE

8922
06:17:01,821 --> 06:17:02,188
DEGENERATION.

8923
06:17:02,188 --> 06:17:05,892
HERE WE TAKE CELLS FROM THE

8924
06:17:05,892 --> 06:17:09,362
PATIENT, WE DIFFERENTIATE INTO

8925
06:17:09,362 --> 06:17:09,796
CARTILAGE PHENOTYPE.

8926
06:17:09,796 --> 06:17:10,897
AND BY DIFFERENTIATING CELLS

8927
06:17:10,897 --> 06:17:13,299
THEN THE CELLS ARE ABLE TO GET

8928
06:17:13,299 --> 06:17:15,501
INCORPORATED AND THEY DO GET

8929
06:17:15,501 --> 06:17:16,702
RETAINED INSIDE THE BODY.

8930
06:17:16,702 --> 06:17:19,872
THIS IS ONE OF THOSE PATIENTS, A

8931
06:17:19,872 --> 06:17:21,407
TRIAL THAT WAS DONE, YOU CAN SEE

8932
06:17:21,407 --> 06:17:25,244
THE AREA OF THE EROSION ON THE

8933
06:17:25,244 --> 06:17:26,445
LEFT, AND THE REGENERATED AREA

8934
06:17:26,445 --> 06:17:29,582
ON THE RIGHT.

8935
06:17:29,582 --> 06:17:35,555
YOU CAN SEE FUNCTIONAL DAILY

8936
06:17:35,555 --> 06:17:36,389
LIVING, SYMPTOM IMPROVEMENT,

8937
06:17:36,389 --> 06:17:38,925
IMPROVEMENTS OF THESE PATIENTS,

8938
06:17:38,925 --> 06:17:39,692
PUBLISHED IN SCIENCE ADVANCES IN

8939
06:17:39,692 --> 06:17:40,626
APRIL OF THIS YEAR.

8940
06:17:40,626 --> 06:17:43,930
YOU CAN SEE THIS WAS A PATIENT

8941
06:17:43,930 --> 06:17:46,966
SERIES WITH ALL THE WORK THAT

8942
06:17:46,966 --> 06:17:51,437
WENT BEHIND IT, FORMING TRUE

8943
06:17:51,437 --> 06:17:53,172
ELASTIC CARTILAGE.

8944
06:17:53,172 --> 06:17:56,509
NOW WE REPEATING WITH PLACENTAL

8945
06:17:56,509 --> 06:18:00,546
STEM CELLS, DOING THE WHOLE

8946
06:18:00,546 --> 06:18:02,715
THING, DIFFERENTIATE CELLS.

8947
06:18:02,715 --> 06:18:06,085
WE POSTULATED ABOUT 25 YEARS AGO

8948
06:18:06,085 --> 06:18:07,954
WHETHER THERE WOULD BE A STEM

8949
06:18:07,954 --> 06:18:10,890
CELL PRESENT IN AMNIOTIC FLUID

8950
06:18:10,890 --> 06:18:12,792
AND PLACENTA, AND IT WAS A

8951
06:18:12,792 --> 06:18:14,861
FISHING EXPEDITION BUT DID FIND

8952
06:18:14,861 --> 06:18:16,929
A STEM CELL WITHIN THE AMNIOTIC

8953
06:18:16,929 --> 06:18:18,130
FLUID AND PLACEBO THAT WOULD

8954
06:18:18,130 --> 06:18:20,766
GIVE RISE TO ALL THREE GERM

8955
06:18:20,766 --> 06:18:21,267
LAYERS.

8956
06:18:21,267 --> 06:18:22,535
THIS IS A SEED KIT ISOLATION

8957
06:18:22,535 --> 06:18:24,704
THAT ALLOWS YOU TO GO INTO ALL

8958
06:18:24,704 --> 06:18:27,473
THREE GERM LAYERS.

8959
06:18:27,473 --> 06:18:29,609
THE CELLS, THIS SLIDE YOU SEE

8960
06:18:29,609 --> 06:18:31,077
HERE TOOK THREE YEARS TO CREATE.

8961
06:18:31,077 --> 06:18:34,580
YOU HAD TO PROVE THE CELLS WERE

8962
06:18:34,580 --> 06:18:36,315
CLONAL AND YOU COULD GET ONE

8963
06:18:36,315 --> 06:18:40,019
CELL FROM ONE CELL TO HAVE

8964
06:18:40,019 --> 06:18:43,089
CLONALITY UNTIL THREE GERM 

8965
06:18:43,089 --> 06:18:44,724
LAYERS IN THE DERM.

8966
06:18:44,724 --> 06:18:47,960
THE CELLS HAD MARKERS CONSISTENT

8967
06:18:47,960 --> 06:18:49,862
WITH EMBRYONIC CELLS INCLUDING

8968
06:18:49,862 --> 06:18:51,030
SOX2, MARKERS CONSISTENT WITH

8969
06:18:51,030 --> 06:18:52,064
ADULT STEM CELLS.

8970
06:18:52,064 --> 06:18:53,799
WHEN YOU LOOK AT A STEMLESS

8971
06:18:53,799 --> 06:18:59,171
ANALYSIS IT'S VERY CLOSE LIP 

8972
06:18:59,171 --> 06:19:02,174
RELATED TO iPS AND HSLs, NOT

8973
06:19:02,174 --> 06:19:05,511
AS MUCH ADULT CELLS.

8974
06:19:05,511 --> 06:19:06,545
PRESERVE TELOMERE LENGTH, BUT

8975
06:19:06,545 --> 06:19:08,047
THEY DON'T FORM THE TUMORS.

8976
06:19:08,047 --> 06:19:09,148
THAT'S THE KEY.

8977
06:19:09,148 --> 06:19:11,584
THEY DON'T FORM THE TERATOMAS.

8978
06:19:11,584 --> 06:19:15,354
AND SO THESE CELLS CAN BE USED

8979
06:19:15,354 --> 06:19:16,155
AS ANTI-INFLAMMATORY CELL, LIKE

8980
06:19:16,155 --> 06:19:18,024
YOU WOULD OTHER CELL TYPES BUT

8981
06:19:18,024 --> 06:19:20,559
THEY HAVE MUCH HIGHER

8982
06:19:20,559 --> 06:19:21,827
ANTI-INFLAMMATORY PROPERTIES,

8983
06:19:21,827 --> 06:19:24,530
AND YOU CAN USE THEM FOR

8984
06:19:24,530 --> 06:19:25,998
IMMUNOMODULATION, OR YOU CAN USE

8985
06:19:25,998 --> 06:19:28,034
THEM TO DIFFERENTIATE THEM AND

8986
06:19:28,034 --> 06:19:29,302
TO TAKE THEM INTO SPECIFIC

8987
06:19:29,302 --> 06:19:30,136
TISSUE TYPES.

8988
06:19:30,136 --> 06:19:31,570
AND SO THESE CELLS, YOU CAN GET

8989
06:19:31,570 --> 06:19:37,376
THEM JUST AT THE TIME OF BIRTH,

8990
06:19:37,376 --> 06:19:37,944
STORE THEM.

8991
06:19:37,944 --> 06:19:39,679
THEY DON'T FORM THE TUMORS, LIKE

8992
06:19:39,679 --> 06:19:42,782
OTHER CELL TYPES RAPID LIP

8993
06:19:42,782 --> 06:19:44,684
EXPAND AND DO GO INTO THREE GERM

8994
06:19:44,684 --> 06:19:47,787
LAYERS AND CAN BE STORED AT THE

8995
06:19:47,787 --> 06:19:49,755
TIME OF BIRTH, AND CLONAL SO YOU

8996
06:19:49,755 --> 06:19:51,157
CAN KEEP THEM GOING FOR LONG

8997
06:19:51,157 --> 06:19:52,458
PERIODS OF TIME.

8998
06:19:52,458 --> 06:19:54,493
NO CELL IS PERFECT, NEITHER IS

8999
06:19:54,493 --> 06:19:55,127
THIS ONE.

9000
06:19:55,127 --> 06:19:56,429
THE WEAKNESS WITH THE CELL IS

9001
06:19:56,429 --> 06:19:58,130
THAT IT REALLY TAKES YOU LONGER

9002
06:19:58,130 --> 06:19:58,998
TO DRIVE IT.

9003
06:19:58,998 --> 06:20:01,901
SO, FOR EXAMPLE, WITH A HUMAN

9004
06:20:01,901 --> 06:20:04,904
EMBRYONIC OR iPS CELL YOU CAN

9005
06:20:04,904 --> 06:20:07,506
DRIVE TO LIVER CELL WITHIN 14

9006
06:20:07,506 --> 06:20:09,742
CELLS, 10 DAYS EVEN, WITH THESE

9007
06:20:09,742 --> 06:20:11,777
IT TAKES 20 TO 21 DAYS TO DRIVE

9008
06:20:11,777 --> 06:20:13,179
TO THAT PHENOTYPE, THAT'S ALSO

9009
06:20:13,179 --> 06:20:15,581
THE SAME PROPERTY THAT ALLOWS

9010
06:20:15,581 --> 06:20:18,584
CELLS TO -- CELLS ARE JUST NOT

9011
06:20:18,584 --> 06:20:20,753
AS PRIMITIVE, MORE ESTABLISHED.

9012
06:20:20,753 --> 06:20:23,356
THIS ALSO IS HIGHLIGHTED IN

9013
06:20:23,356 --> 06:20:24,757
NATURE BIOTECHNOLOGY, STEM CELLS

9014
06:20:24,757 --> 06:20:26,759
FROM THE WOMB, AFTER ALL THESE

9015
06:20:26,759 --> 06:20:29,695
YEARS ENTERING THE CELLS INTO

9016
06:20:29,695 --> 06:20:31,897
THE CLINIC, CLINICAL TRIALS, WE

9017
06:20:31,897 --> 06:20:33,766
HAD TO PROVE SAFETY BEFORE DOING

9018
06:20:33,766 --> 06:20:34,200
THAT.

9019
06:20:34,200 --> 06:20:35,368
SO TO SUMMARIZE WHAT I'VE TRIED

9020
06:20:35,368 --> 06:20:37,970
TO DO TODAY IS GIVE AN OVERVIEW

9021
06:20:37,970 --> 06:20:39,505
OF USING TISSUE-SPECIFIC CELLS.

9022
06:20:39,505 --> 06:20:41,207
THE ADVANTAGE IS THAT ONCE YOU

9023
06:20:41,207 --> 06:20:43,442
DRIVE THEM, THEY ARE GOING TO

9024
06:20:43,442 --> 06:20:45,344
GET INCORPORATED INTO THE TISSUE

9025
06:20:45,344 --> 06:20:47,380
AND BE THERE LONG TERM.

9026
06:20:47,380 --> 06:20:48,848
CHALLENGES ARE COST OF

9027
06:20:48,848 --> 06:20:50,549
PRODUCTION AND ABILITY TO MAKE

9028
06:20:50,549 --> 06:20:53,586
SURE THAT YOU HAVE THE

9029
06:20:53,586 --> 06:20:55,721
FACILITIES NECESSARY TO PRODUCE

9030
06:20:55,721 --> 06:20:57,757
THESE.

9031
06:20:57,757 --> 06:20:58,824
THIS IS A MULTI-DISCIPLINARY

9032
06:20:58,824 --> 06:21:00,192
TEAM, I'VE PRESENTED A LOT OF

9033
06:21:00,192 --> 06:21:01,327
WORK IN THIS AREA.

9034
06:21:01,327 --> 06:21:06,799
THIS IS, YOU KNOW, IT TAKES CELL

9035
06:21:06,799 --> 06:21:08,467
BIOLOGISTS, MOLECULAR

9036
06:21:08,467 --> 06:21:10,703
BIOLOGISTS, PHYSIOLOGIES, WE

9037
06:21:10,703 --> 06:21:12,338
HAVE OUR OWN FACILITY WITH A

9038
06:21:12,338 --> 06:21:15,274
TEAM THAT ALLOWS YOU TO RUN

9039
06:21:15,274 --> 06:21:15,608
THESE TRIALS.

9040
06:21:15,608 --> 06:21:20,346
AND THIS IS A LIST OF OUR

9041
06:21:20,346 --> 06:21:21,781
FACULTY AND STAFF, AND OUR

9042
06:21:21,781 --> 06:21:23,516
FUNDING SOURCES THAT MADE THIS

9043
06:21:23,516 --> 06:21:24,150
WORK POSSIBLE.

9044
06:21:24,150 --> 06:21:27,486
THANK YOU FOR YOUR ATTENTION.

9045
06:21:27,486 --> 06:21:33,526
 

9046
06:21:33,526 --> 06:21:43,569
 

9047
06:21:44,103 --> 06:21:45,571
>> THANK YOU, TONY.

9048
06:21:45,571 --> 06:21:47,473
WHEN YOU TRANSPLANT THE LIVER

9049
06:21:47,473 --> 06:21:48,841
CELLS, YOU SAID THAT YOU COULD

9050
06:21:48,841 --> 06:21:51,844
ONLY GET THROUGH THE LARGEST

9051
06:21:51,844 --> 06:21:53,446
VESSELS BECAUSE OF CLOGGING.

9052
06:21:53,446 --> 06:21:55,347
IF YOU DO THAT, YOU WAIT SOME

9053
06:21:55,347 --> 06:21:59,018
TIME WHILE IT'S IN THE ANIMAL OR

9054
06:21:59,018 --> 06:22:00,653
WHEREVER YOU'RE PUTTING IT TO

9055
06:22:00,653 --> 06:22:01,787
ENSURE IT DO YOU GET

9056
06:22:01,787 --> 06:22:04,056
REGENERATION IN THE LIVER IN

9057
06:22:04,056 --> 06:22:05,624
SUCH TREMENDOUS REGENERATION ON

9058
06:22:05,624 --> 06:22:08,060
ITS OWN, SO DOES THAT ACT AS

9059
06:22:08,060 --> 06:22:10,296
FEEDER OR SEED POPULATION FOR

9060
06:22:10,296 --> 06:22:10,930
REGENERATING THE LIVER

9061
06:22:10,930 --> 06:22:11,564
ALTOGETHER?

9062
06:22:11,564 --> 06:22:13,299
>> IT DOES.

9063
06:22:13,299 --> 06:22:14,300
IT REALLY DOES, ROSEMARY IS

9064
06:22:14,300 --> 06:22:15,701
QUICK TO SEE.

9065
06:22:15,701 --> 06:22:18,137
I MUST SAY, I THINK THE KEY

9066
06:22:18,137 --> 06:22:21,073
THERE IS TO REPLACEMENT TAKE THE

9067
06:22:21,073 --> 06:22:22,641
CENTRAL PORTION OF THE LIVER

9068
06:22:22,641 --> 06:22:24,977
THAT HAS ALL THOSE LARGE VESSELS

9069
06:22:24,977 --> 06:22:27,580
BECAUSE FURTHER OUT YOU GET, THE

9070
06:22:27,580 --> 06:22:28,214
SMALLER CAPILLARIES.

9071
06:22:28,214 --> 06:22:30,282
SO I THINK THERE'S A STRATEGY

9072
06:22:30,282 --> 06:22:31,617
THERE WHERE YOU CAN TAKE THE

9073
06:22:31,617 --> 06:22:33,586
CENTRAL PORTION WHERE YOU HAVE

9074
06:22:33,586 --> 06:22:36,388
THE LARGE VESSELS, USE THAT AS A

9075
06:22:36,388 --> 06:22:36,689
SEED.

9076
06:22:36,689 --> 06:22:38,257
AS YOU KNOW, THAT'S THE STRATEGY

9077
06:22:38,257 --> 06:22:40,993
WE USE WITH THE KIDNEY, YOU

9078
06:22:40,993 --> 06:22:43,529
DON'T GET INTO KIDNEY FAILURE

9079
06:22:43,529 --> 06:22:45,898
TILL OVER 90% OF ORGAN IS GONE.

9080
06:22:45,898 --> 06:22:48,200
YOU WANT THE EXTRA 10%.

9081
06:22:48,200 --> 06:22:50,302
SO I THINK THAT WOULD BE THE 

9082
06:22:50,302 --> 06:22:57,209
RIGHT STRATEGY TO PURSUE.

9083
06:22:57,209 --> 06:22:59,912
>> FABULOUS TALK.

9084
06:22:59,912 --> 06:23:02,414
iPS VERSUS STEM CELLS, IF YOU

9085
06:23:02,414 --> 06:23:04,450
CAN EXPAND TISSUE STEM CELLS TO

9086
06:23:04,450 --> 06:23:08,587
ENOUGH CLINICAL SCALE CAN YOU 

9087
06:23:08,587 --> 06:23:10,523
OVER ADVANTAGES AND

9088
06:23:10,523 --> 06:23:11,123
DISADVANTAGES?

9089
06:23:11,123 --> 06:23:11,457
>> ABSOLUTELY.

9090
06:23:11,457 --> 06:23:11,857
THANKS, TONY.

9091
06:23:11,857 --> 06:23:15,427
GOOD TO SEE YOU AS WELL.

9092
06:23:15,427 --> 06:23:17,630
THE INTERESTING THING IS, YOU

9093
06:23:17,630 --> 06:23:19,265
KNOW, PLUSES AND MINUSES, RIGHT?

9094
06:23:19,265 --> 06:23:21,000
WE NEED TO THINK THAT THERE'S NO

9095
06:23:21,000 --> 06:23:22,268
PERFECT CELL.

9096
06:23:22,268 --> 06:23:23,869
THAT'S THE BOTTOM LINE, RIGHT?

9097
06:23:23,869 --> 06:23:26,639
THEY ALL HAVE THEIR PLUSES AND

9098
06:23:26,639 --> 06:23:27,907
MINUSES.

9099
06:23:27,907 --> 06:23:29,775
I THINK IT DEPENDS ON THE

9100
06:23:29,775 --> 06:23:31,510
PATIENT INDICATION, RIGHT?

9101
06:23:31,510 --> 06:23:33,279
AND THE CONDITION.

9102
06:23:33,279 --> 06:23:37,550
AND IT ALSO DEPENDS ON, YOU 

9103
06:23:37,550 --> 06:23:38,217
KNOW, IT'S PERSONALIZED

9104
06:23:38,217 --> 06:23:38,584
MEDICINE.

9105
06:23:38,584 --> 06:23:40,085
FOR SOME PEOPLE YOU DON'T HAVE

9106
06:23:40,085 --> 06:23:41,387
THOSE CELLS TO HARVEST.

9107
06:23:41,387 --> 06:23:42,488
THEREFORE STEM CELLS ARE GOING

9108
06:23:42,488 --> 06:23:43,789
TO BE A GREAT RESOURCE.

9109
06:23:43,789 --> 06:23:48,160
FOR SOME PATIENTS YOU DO HAVE 

9110
06:23:48,160 --> 06:23:50,696
THOSE CELLS YOU CAN HARVEST, A

9111
06:23:50,696 --> 06:23:51,297
PERSONALIZED APPROACH USING

9112
06:23:51,297 --> 06:23:53,599
THEIR CELLS IS THE BEST.

9113
06:23:53,599 --> 06:23:54,600
WITH PERSONALIZED APPROACH IT IS

9114
06:23:54,600 --> 06:23:55,634
PATIENT SPECIFIC.

9115
06:23:55,634 --> 06:23:58,470
YOU HAVE TO GROW THOSE CELLS

9116
06:23:58,470 --> 06:23:59,238
EVERY TIME.

9117
06:23:59,238 --> 06:24:00,973
BUT YOU ARE -- YOU DO HAVE

9118
06:24:00,973 --> 06:24:03,375
ADVANTAGE OF NO REJECTION.

9119
06:24:03,375 --> 06:24:05,010
WITH THEM CELL POPULATION YOU

9120
06:24:05,010 --> 06:24:06,312
CAN HAVE UNIVERSAL BANK BUT

9121
06:24:06,312 --> 06:24:08,447
STILL DEALING WITH PROBLEMS OF

9122
06:24:08,447 --> 06:24:09,148
REJECTION.

9123
06:24:09,148 --> 06:24:10,382
I THINK THESE ARE SOME

9124
06:24:10,382 --> 06:24:12,351
CHALLENGES WE HAVE, AND IT

9125
06:24:12,351 --> 06:24:15,020
DEPENDS, IF I'M LOOKING AT A

9126
06:24:15,020 --> 06:24:16,922
20-YEAR-OLD, YOU KNOW, AS

9127
06:24:16,922 --> 06:24:18,023
OPPOSED TO 70-YEAR-OLD, WHAT

9128
06:24:18,023 --> 06:24:18,824
WOULD I DO?

9129
06:24:18,824 --> 06:24:20,960
WHAT WOULD YOU DO?

9130
06:24:20,960 --> 06:24:23,062
THE SAME THING, ARE YOU LOOKING

9131
06:24:23,062 --> 06:24:25,497
AT SOMETHING LIKE KIDNEY FAILURE

9132
06:24:25,497 --> 06:24:30,736
OR SOMETHING LIKE DIABETES? 

9133
06:24:30,736 --> 06:24:33,038
AND SO ALL THOSE FACTORS COME

9134
06:24:33,038 --> 06:24:35,341
INTO PLAY, YOU CAN'T DISCARD ANY

9135
06:24:35,341 --> 06:24:36,141
ONE CELL CATEGORY.

9136
06:24:36,141 --> 06:24:38,611
YOU HAVE TO SAY THIS IS THE MENU

9137
06:24:38,611 --> 06:24:44,950
WE HAVE, AND WHAT IS THE BEST 

9138
06:24:44,950 --> 06:24:46,819
APPROACH FOR THE FUTURE.

9139
06:24:46,819 --> 06:24:48,320
>> WOW!

9140
06:24:48,320 --> 06:24:49,755
THAT'S ALL ONE CAN SAY FOR

9141
06:24:49,755 --> 06:24:50,522
EVERYBODY YOU'VE DONE.

9142
06:24:50,522 --> 06:24:52,825
MAYBE I MISSED THIS.

9143
06:24:52,825 --> 06:24:54,960
WHEN YOU'RE GROWING THE

9144
06:24:54,960 --> 06:24:57,730
AUTOLOGOUS KIDNEY CELLS YOU'RE

9145
06:24:57,730 --> 06:24:59,598
IMPLANTING, HOW ARE THOSE

9146
06:24:59,598 --> 06:25:00,599
ACTUALLY IMPLANTED WITH THE

9147
06:25:00,599 --> 06:25:05,604
QUESTION HOW DO THEY KNOW HOW TO

9148
06:25:05,604 --> 06:25:07,806
HOOK UP WITH COLLECTING SYSTEM,

9149
06:25:07,806 --> 06:25:09,742
EVERY OTHER PART OF THE ANATOMY?

9150
06:25:09,742 --> 06:25:12,745
>> IT'S REALLY
INTERESTING.

9151
06:25:12,745 --> 06:25:14,280
THIS WAS THE BILLION DOLLAR

9152
06:25:14,280 --> 06:25:16,348
QUESTION WHEN WE STARTED THIS

9153
06:25:16,348 --> 06:25:19,084
WORK 30 YEARS AGO, 33 YEARS AGO,

9154
06:25:19,084 --> 06:25:20,619
STARTED TO THINK WE STARTED

9155
06:25:20,619 --> 06:25:21,820
KIDNEY WORK 33 YEARS AGO AND

9156
06:25:21,820 --> 06:25:25,324
COULDN'T GET THE CELLS TO GROW,

9157
06:25:25,324 --> 06:25:27,626
USING MAGNETIC SORTERS TO

9158
06:25:27,626 --> 06:25:35,100
ISOLATE THE GLOMULERAR LINE, WE

9159
06:25:35,100 --> 06:25:36,835
GAVE UP, LET'S GROW THE CELLS

9160
06:25:36,835 --> 06:25:37,736
TOGETHER, THAT'S WHAT WORKED,

9161
06:25:37,736 --> 06:25:38,937
GROWING ALL THE CELLS TOGETHER

9162
06:25:38,937 --> 06:25:44,043
IS WHAT ALLOWED US TO GET CELLS

9163
06:25:44,043 --> 06:25:45,511
TO EXPAND.

9164
06:25:45,511 --> 06:25:47,713
WHEN WE STARTED IMPLANTING INTO

9165
06:25:47,713 --> 06:25:50,082
DEVICES IN THE LABORATORY, THEY

9166
06:25:50,082 --> 06:25:52,885
STARTED FORMING TUBULES.

9167
06:25:52,885 --> 06:25:55,187
AND ACTUALLY FILTERING THE BLOOD

9168
06:25:55,187 --> 06:25:57,423
IN THE MEDIA, SERUM AND MEDIA,

9169
06:25:57,423 --> 06:25:58,324
JUST AMAZING.

9170
06:25:58,324 --> 06:26:00,959
BOOM, THERE IT WENT.

9171
06:26:00,959 --> 06:26:03,362
THE CELLS REALLY DO HAVE ALL THE

9172
06:26:03,362 --> 06:26:06,298
GENETIC INFORMATION TO CREATE A

9173
06:26:06,298 --> 06:26:13,639
WHOLE NEW YOU, DOLLY WAS  CLONED

9174
06:26:13,639 --> 06:26:15,341
WITH ONE CELL.

9175
06:26:15,341 --> 06:26:22,715
THE CELLS HAVE THE PROGRAMMING.

9176
06:26:22,715 --> 06:26:28,520
IF YOU TAKE THE TISSUE, SEVEN OR

9177
06:26:28,520 --> 06:26:30,856
EIGHT LAYERS, NINE MAX, YOU TAKE

9178
06:26:30,856 --> 06:26:32,558
THE CELLS, THAT'S WHAT THEY DO,

9179
06:26:32,558 --> 06:26:35,527
THEY ARE PROGRAMMED TO DO THAT.

9180
06:26:35,527 --> 06:26:37,129
AND SO IT'S INSIDE PROGRAMMING

9181
06:26:37,129 --> 06:26:39,765
THAT ALLOWS CELLS TO DO WHAT

9182
06:26:39,765 --> 06:26:42,234
THEY NEED TO DO, AND YOU SAW THE

9183
06:26:42,234 --> 06:26:42,468
SLIDES.

9184
06:26:42,468 --> 06:26:45,037
YOU SAW THE NEW NEPHRONS.

9185
06:26:45,037 --> 06:26:45,838
THEY DO RECONNECT.

9186
06:26:45,838 --> 06:26:48,774
I THINK PART OF THE PROBLEM IS

9187
06:26:48,774 --> 06:26:50,542
THAT WE HAVE BEEN TAUGHT, YOU

9188
06:26:50,542 --> 06:26:54,012
KNOW, FOR SO MANY DECADES, YOU

9189
06:26:54,012 --> 06:26:56,515
KNOW, LIKE PLASTIC SURGEONS,

9190
06:26:56,515 --> 06:26:57,116
RIGHT?

9191
06:26:57,116 --> 06:26:57,683
PLASTIC SURGEONS ARE TAUGHT

9192
06:26:57,683 --> 06:27:00,252
THAT, YOU KNOW, YOU'RE GOING TO

9193
06:27:00,252 --> 06:27:02,521
CREATE A TISSUE TRANSFER, AND

9194
06:27:02,521 --> 06:27:04,056
YOU'RE PUTTING A FLAP, AND YOU

9195
06:27:04,056 --> 06:27:05,724
ARE MOVING A FLAP OVER.

9196
06:27:05,724 --> 06:27:06,959
THE WAY YOU MOVE THE FLAP YOU

9197
06:27:06,959 --> 06:27:08,994
HAVE TO MAKE SURE IT HAS THE

9198
06:27:08,994 --> 06:27:14,366
RIGHT WIDTH COMPARED TO LENGTH,

9199
06:27:14,366 --> 06:27:17,536
THE RIGHT VESSELS TO SURVIVE.

9200
06:27:17,536 --> 06:27:23,776
WE THINK WILL REGEN MED, IT IS

9201
06:27:23,776 --> 06:27:29,581
END OF THE  DAY YOU'RE PUTTING

9202
06:27:29,581 --> 06:27:31,650
IN CELLS, NOT TISSUE, YOU HAVE A

9203
06:27:31,650 --> 06:27:42,194
BETTER CHANCE THAN WITH A FLAP. 

9204
06:27:53,272 --> 06:27:55,107
>> IT'S A GREAT QUESTION.

9205
06:27:55,107 --> 06:27:56,175
OTHER EXAMPLES.

9206
06:27:56,175 --> 06:27:59,478
WE GO IN, WE DO KIDNEY SURGERY,

9207
06:27:59,478 --> 06:27:59,878
RIGHT?

9208
06:27:59,878 --> 06:28:04,183
AND IN THE OLD DAYS YOU WOULD

9209
06:28:04,183 --> 06:28:06,685
OPEN THE KIDNEY UP BEFORE YOU

9210
06:28:06,685 --> 06:28:08,120
COULD SHOCK THESE KIDNEY STONES,

9211
06:28:08,120 --> 06:28:10,155
THE ONLY WAY COULD YOU GET A

9212
06:28:10,155 --> 06:28:11,723
KIDNEY STONE OUT WAS TO GO IN

9213
06:28:11,723 --> 06:28:15,327
AND OPEN THE ENTIRE KIDNEY UP

9214
06:28:15,327 --> 06:28:17,529
LIKE A -- YOU KNOW, AND JUST

9215
06:28:17,529 --> 06:28:19,064
FILLET IT OPEN, GO IN AND GO

9216
06:28:19,064 --> 06:28:20,466
THROUGH THE WHOLE THING AND TAKE

9217
06:28:20,466 --> 06:28:22,634
THE STONES OUT AND PUT IT BACK

9218
06:28:22,634 --> 06:28:23,035
TOGETHER.

9219
06:28:23,035 --> 06:28:24,937
AND GUESS WHAT, YOU GO BACK FOR

9220
06:28:24,937 --> 06:28:26,738
ANOTHER KIDNEY STONE, YOU CAN'T

9221
06:28:26,738 --> 06:28:27,773
TELL THAT THERE'S A SCAR INSIDE

9222
06:28:27,773 --> 06:28:28,774
THE BODY.

9223
06:28:28,774 --> 06:28:30,309
YOU CAN'T SEE ANYTHING.

9224
06:28:30,309 --> 06:28:33,512
AND SO THE BODY HAS A NATURAL

9225
06:28:33,512 --> 06:28:35,214
HEALING ABILITY.

9226
06:28:35,214 --> 06:28:39,218
LIKE WHAT WAS SAID ABOUT THE

9227
06:28:39,218 --> 06:28:39,618
LIVER, REGENERATE.

9228
06:28:39,618 --> 06:28:41,920
YOU KNOCK A THIRD OUT, YOU COME

9229
06:28:41,920 --> 06:28:43,455
BACK WITH AN MRI, THERE IT'S THE

9230
06:28:43,455 --> 06:28:44,256
NEW LIVER AGAIN.

9231
06:28:44,256 --> 06:28:45,791
HOW DID THAT HAPPEN, RIGHT?

9232
06:28:45,791 --> 06:28:49,127
IT HAPPENS ONE CELL AT A TIME.

9233
06:28:49,127 --> 06:28:50,562
CELLS GET IN THERE, DO WHAT THEY

9234
06:28:50,562 --> 06:28:52,764
ARE SUPPOSED TO DO AND RECONNECT

9235
06:28:52,764 --> 06:28:54,500
LIKE THEY ARE SUPPOSED TO.

9236
06:28:54,500 --> 06:28:56,268
WE SEE IT EVERY TIME WE DO

9237
06:28:56,268 --> 06:28:57,269
SURGERY.

9238
06:28:57,269 --> 06:28:59,438
EVERY TIME YOU CUT, YOU'RE

9239
06:28:59,438 --> 06:29:01,740
SPLITTING THE TISSUE, AND YET IT

9240
06:29:01,740 --> 06:29:02,040
HEALS BACK.

9241
06:29:02,040 --> 06:29:03,375
SO, THAT'S JUST THE WAY THE BODY

9242
06:29:03,375 --> 06:29:04,176
IS DESIGNED.

9243
06:29:04,176 --> 06:29:06,311
IT'S VERY HARD TO CONCEPTUALIZE

9244
06:29:06,311 --> 06:29:15,087
ACTUALLY BUT THAT'S WHAT OCCURS.

9245
06:29:15,087 --> 06:29:17,523
>> THANK YOU.

9246
06:29:17,523 --> 06:29:19,258
MY QUESTION, CONNIE, STANFORD,

9247
06:29:19,258 --> 06:29:20,792
MY QUESTION IS RELATED TO

9248
06:29:20,792 --> 06:29:22,861
TRANSPLANTATION OF THE KIDNEY

9249
06:29:22,861 --> 06:29:24,596
CELLS, PUTTING IT BACK IN A

9250
06:29:24,596 --> 06:29:24,963
DISEASED KIDNEY.

9251
06:29:24,963 --> 06:29:27,032
IS THERE A POINT WHERE THE

9252
06:29:27,032 --> 06:29:30,202
KIDNEY IS SO DISEASED THAT IT

9253
06:29:30,202 --> 06:29:31,036
WOULD COMPROMISE THE CELLS SO

9254
06:29:31,036 --> 06:29:33,405
THAT'S ONE SIDE OF THE QUESTION,

9255
06:29:33,405 --> 06:29:35,474
AND THE OTHER SIDE IS ARE THE

9256
06:29:35,474 --> 06:29:37,109
CELLS YOU PUT IN, DO THEY

9257
06:29:37,109 --> 06:29:40,846
ACTUALLY HAVE A POSITIVE EFFECT

9258
06:29:40,846 --> 06:29:43,248
ON THE SURROUNDING DISEASE

9259
06:29:43,248 --> 06:29:43,482
TISSUE?

9260
06:29:43,482 --> 06:29:45,884
>> AMAZINGLY GOOD
QUESTION.

9261
06:29:45,884 --> 06:29:46,985
THAT'S A GREAT QUESTION.

9262
06:29:46,985 --> 06:29:49,388
I'LL TAKE THAT ONE STEP AT A

9263
06:29:49,388 --> 06:29:50,255
TIME.

9264
06:29:50,255 --> 06:29:52,891
THE FACT IS THAT THE WAY THAT

9265
06:29:52,891 --> 06:29:54,860
TISSUES END UP WITH FAILURE IS

9266
06:29:54,860 --> 06:30:02,301
DUE TO SCAR. 

9267
06:30:02,301 --> 06:30:05,103
PROGRAMMED CELL DEATH,

9268
06:30:05,103 --> 06:30:06,238
APOPTOSIS, REGARDLESS OF

9269
06:30:06,238 --> 06:30:10,876
INSURANCE, HIGH BLOOD PRESSURE,

9270
06:30:10,876 --> 06:30:14,012
DIABETES, PROGRAMMED CELL DEATH,

9271
06:30:14,012 --> 06:30:15,647
FIBROTIC POSITION, YOU DO AWAY

9272
06:30:15,647 --> 06:30:17,015
WITH NORMAL TISSUE.

9273
06:30:17,015 --> 06:30:19,051
SO I'M GOING TO JUST SHIFT OVER

9274
06:30:19,051 --> 06:30:20,719
HERE A LITTLE BIT, TO TELL YOU

9275
06:30:20,719 --> 06:30:23,589
THAT IT'S NOT THAT THE CELLS

9276
06:30:23,589 --> 06:30:24,256
DON'T REPRODUCE.

9277
06:30:24,256 --> 06:30:25,524
THAT'S NOT WHAT IS REALLY

9278
06:30:25,524 --> 06:30:25,891
HAPPENING.

9279
06:30:25,891 --> 06:30:27,726
WHAT'S HAPPENING IS THAT YOU

9280
06:30:27,726 --> 06:30:29,294
HAVE TOO MUCH SCAR TISSUE FOR

9281
06:30:29,294 --> 06:30:31,096
THE CELLS TO REGENERATE.

9282
06:30:31,096 --> 06:30:32,898
THAT'S WHAT'S GOING ON.

9283
06:30:32,898 --> 06:30:37,903
PRIME EXAMPLE IS DIABETES,

9284
06:30:37,903 --> 06:30:38,437
RIGHT?

9285
06:30:38,437 --> 06:30:39,004
JUVENILE DIABETES.

9286
06:30:39,004 --> 06:30:40,806
IT'S BEEN SHOWN, RIGHT?

9287
06:30:40,806 --> 06:30:42,674
THIS WAS OUR HYPOTHESIS BUT WE

9288
06:30:42,674 --> 06:30:49,448
FINALLY SAW IT OCCUR IN

9289
06:30:49,448 --> 06:30:50,515
REAL-TIME LIFE.

9290
06:30:50,515 --> 06:30:52,351
WHAT HAPPENS IN JUVENILE

9291
06:30:52,351 --> 06:30:53,452
DIABETES THE CELLS, IT'S NOT

9292
06:30:53,452 --> 06:30:55,120
THAT YOU STOP PRODUCING CELLS,

9293
06:30:55,120 --> 06:30:56,555
IT'S THE IMMUNE SYSTEM IS

9294
06:30:56,555 --> 06:30:58,624
ATTACKING THE CELLS THAT YOU

9295
06:30:58,624 --> 06:31:00,058
HAVE, YOUR BODY KEEPS PRODUCING

9296
06:31:00,058 --> 06:31:02,361
CELLS, YOUR BODY KEEPS ATTACKING

9297
06:31:02,361 --> 06:31:03,061
THEM, KEEPS FORMING SCAR TISSUE

9298
06:31:03,061 --> 06:31:06,665
AND THEN YOU END UP WITH A SCAR

9299
06:31:06,665 --> 06:31:07,966
TISSUE, HIGH SUGAR.

9300
06:31:07,966 --> 06:31:12,638
IT'S NOT THAT YOUR CELLS STOP

9301
06:31:12,638 --> 06:31:13,639
REPRODUCING.

9302
06:31:13,639 --> 06:31:16,608
THE FIBROTIC CHALLENGE IN REGEN

9303
06:31:16,608 --> 06:31:19,311
MED IS THE NUMBER ONE CHALLENGE

9304
06:31:19,311 --> 06:31:20,579
BECAUSE REGARDLESS OF THE

9305
06:31:20,579 --> 06:31:21,380
DISEASES YOU'RE ENCOUNTERING AT

9306
06:31:21,380 --> 06:31:24,783
THE END OF THE DAY IS THE

9307
06:31:24,783 --> 06:31:26,351
DISEASE THAT IS BASED ON

9308
06:31:26,351 --> 06:31:28,720
FIBROSIS, IF YOU CAN GET RID OF

9309
06:31:28,720 --> 06:31:30,622
FIBROSIS YOU CAN GIVE THE TISSUE

9310
06:31:30,622 --> 06:31:32,124
POWER TO REGENERATE.

9311
06:31:32,124 --> 06:31:34,059
FOR THE KIDNEY, GETTING BACK TO

9312
06:31:34,059 --> 06:31:36,061
THE KIDNEY, PHASE 1 IS TO USE

9313
06:31:36,061 --> 06:31:39,398
THESE CELLS THAT YOU CAN PUT IN,

9314
06:31:39,398 --> 06:31:40,866
AND YOU'RE BASICALLY CREATING

9315
06:31:40,866 --> 06:31:42,968
NEW SPACE WITH THE COLLAGEN

9316
06:31:42,968 --> 06:31:44,469
YOU'RE PUTTING IN, CREATING NEW

9317
06:31:44,469 --> 06:31:46,605
SPACE FOR CELLS TO GROW INTO.

9318
06:31:46,605 --> 06:31:48,540
PHASE 2 IS TO CREATE A WAFER

9319
06:31:48,540 --> 06:31:50,742
THAT YOU CAN PUT IN, PLUG AND

9320
06:31:50,742 --> 06:31:54,012
PLAY TYPE OF THING.

9321
06:31:54,012 --> 06:32:04,489
AND IT DEPENDS ON SEVERITY,

9322
06:32:05,023 --> 06:32:08,060
RIEPT NOW THEY ARE ON THE WAIT

9323
06:32:08,060 --> 06:32:11,029
TO KIDNEY FAILURE AND DIALYSIS,

9324
06:32:11,029 --> 06:32:12,597
HOPEFULLY WE CAN ADVANCE TO

9325
06:32:12,597 --> 06:32:16,535
OTHER POPULATION AREAS.

9326
06:32:16,535 --> 06:32:17,202
>> LAST QUESTION, VERY

9327
06:32:17,202 --> 06:32:17,803
INTERESTING.

9328
06:32:17,803 --> 06:32:20,272
I WONDER IF YOU WOULD DISCUSS

9329
06:32:20,272 --> 06:32:23,008
ONE OR TWO OF THE MOST

9330
06:32:23,008 --> 06:32:24,209
SIGNIFICANT REGULATORY

9331
06:32:24,209 --> 06:32:30,248
CHALLENGES THAT UP HAD WITHIN

9332
06:32:30,248 --> 06:32:30,749
THESE CLINICAL TRIALS.

9333
06:32:30,749 --> 06:32:33,985
>> WE WERE WAY TOO EARLY.

9334
06:32:33,985 --> 06:32:36,555
YOU KNOW, THE FDA KEPT CHANGING

9335
06:32:36,555 --> 06:32:37,656
THE NEEDLE.

9336
06:32:37,656 --> 06:32:42,594
THEY KEPT CHANGING THE GOAL

9337
06:32:42,594 --> 06:32:43,028
LINE.

9338
06:32:43,028 --> 06:32:45,664
I'LL NEVER FORGET, WHEN WE

9339
06:32:45,664 --> 06:32:50,001
IMPLANTED THE BLADDER, I GOT A

9340
06:32:50,001 --> 06:32:52,037
PHONE CALL FROM PHIL, THE HEAD

9341
06:32:52,037 --> 06:32:54,706
OF THE  FDA.

9342
06:32:54,706 --> 06:32:57,776
IS CELIA HERE IN THE AUDIENCE?

9343
06:32:57,776 --> 06:33:00,512
RICHARD IS HERE.

9344
06:33:00,512 --> 06:33:02,414
YOU KNEW -- YOU WERE BACK IN

9345
06:33:02,414 --> 06:33:03,115
THOSE DAYS.

9346
06:33:03,115 --> 06:33:04,349
I GET A PHONE CALL.

9347
06:33:04,349 --> 06:33:06,151
OH MY GOSH, WHAT DID I -- WHEN

9348
06:33:06,151 --> 06:33:08,220
WE PUT IN THE BLADDER IT WAS NOT

9349
06:33:08,220 --> 06:33:09,521
BEING REGULATED.

9350
06:33:09,521 --> 06:33:10,589
THERE WAS NO REGULATIONS BECAUSE

9351
06:33:10,589 --> 06:33:13,125
THERE WAS NO SUCH THING.

9352
06:33:13,125 --> 06:33:14,760
SO THERE WERE NO REGULATIONS

9353
06:33:14,760 --> 06:33:15,060
WHATSOEVER.

9354
06:33:15,060 --> 06:33:16,862
AND SO I GOT A CALL FROM HIM IN

9355
06:33:16,862 --> 06:33:18,063
MY OFFICE.

9356
06:33:18,063 --> 06:33:20,031
I WAS STILL IN BOSTON.

9357
06:33:20,031 --> 06:33:23,869
I  ANSWERED THE PHONE.

9358
06:33:23,869 --> 06:33:27,472
NICE OF HE SAID NICE PAPER, WE

9359
06:33:27,472 --> 06:33:30,442
DON'T REGULAR IT, SO YOU'RE

9360
06:33:30,442 --> 06:33:30,776
OKAY.

9361
06:33:30,776 --> 06:33:32,711
BUT WHY ARE YOU CALLING ME?

9362
06:33:32,711 --> 06:33:37,115
I'D LOVE FOR YOU TO VISIT ME.

9363
06:33:37,115 --> 06:33:38,683
NEXT TIME YOU'RE IN D.C.

9364
06:33:38,683 --> 06:33:40,952
I HAD A STUDY SECTION THE MONTH

9365
06:33:40,952 --> 06:33:42,921
LATER, CAME TO D.C.

9366
06:33:42,921 --> 06:33:43,722
WENT TO SEE PHIL.

9367
06:33:43,722 --> 06:33:45,357
AND, YOU KNOW, PHIL SAID HELLO.

9368
06:33:45,357 --> 06:33:49,094
I WANT YOU TO KNOW WE WANT TO

9369
06:33:49,094 --> 06:33:50,295
START LOOKING AT THIS AND

9370
06:33:50,295 --> 06:33:51,329
REGULATING THIS.

9371
06:33:51,329 --> 06:33:52,030
WE'RE THE GOVERNMENT, HERE TO

9372
06:33:52,030 --> 06:33:52,664
HELP YOU.

9373
06:33:52,664 --> 06:33:53,698
HE MEANT IT.

9374
06:33:53,698 --> 06:33:55,667
HE REALLY MEANT IT.

9375
06:33:55,667 --> 06:33:58,069
AND SO THEN HE INTRODUCED ME TO

9376
06:33:58,069 --> 06:33:59,805
SOMEONE IN THE ROOM, AND HE SAID

9377
06:33:59,805 --> 06:34:01,039
BY THE WAY, THIS IS THE

9378
06:34:01,039 --> 06:34:03,208
INDIVIDUAL WHO IS GOING TO BE

9379
06:34:03,208 --> 06:34:04,442
LOOKING AT THIS EXTENSIVELY.

9380
06:34:04,442 --> 06:34:06,411
AND THAT INDIVIDUAL IS ACTUALLY

9381
06:34:06,411 --> 06:34:07,379
STEVE BAUER.

9382
06:34:07,379 --> 06:34:08,613
AND SO STEVE BAUER WAS RIGHT

9383
06:34:08,613 --> 06:34:10,115
THERE ACROSS FROM THE LINE,

9384
06:34:10,115 --> 06:34:11,983
THAT'S WHEN I MET STEVE.

9385
06:34:11,983 --> 06:34:14,386
STEVE WAS AT THE FDA FOR 31

9386
06:34:14,386 --> 06:34:15,821
YEARS, AND HE WAS BRANCH CHIEF

9387
06:34:15,821 --> 06:34:17,689
OF CELL AND TISSUE THERAPY FOR

9388
06:34:17,689 --> 06:34:19,391
THE LAST 16 YEARS.

9389
06:34:19,391 --> 06:34:20,492
HE RETIRED IN NOVEMBER.

9390
06:34:20,492 --> 06:34:22,594
AND I TELL YOU THE SMARTEST

9391
06:34:22,594 --> 06:34:27,265
THING WE EVER DID WAS RECRUIT

9392
06:34:27,265 --> 06:34:31,670
STEVE. 

9393
06:34:31,670 --> 06:34:36,908
HE'S ALSO WITH US AT THE REGEN

9394
06:34:36,908 --> 06:34:38,243
MED, TRYING TO HELP COMPANIES

9395
06:34:38,243 --> 06:34:38,610
REGULATE.

9396
06:34:38,610 --> 06:34:40,612
HE WILL BE THE FIRST TO TELL YOU

9397
06:34:40,612 --> 06:34:41,947
THE REASON THE GOAL LINE KEPT

9398
06:34:41,947 --> 06:34:43,782
MOVING WE WERE LEARNING MORE AS

9399
06:34:43,782 --> 06:34:45,684
WE WENT ALONG, VERY IMPORTANT

9400
06:34:45,684 --> 06:34:49,054
NOT TO HURT PATIENTS, THE NUMBER

9401
06:34:49,054 --> 06:34:49,588
ONE DIRECTIVE.

9402
06:34:49,588 --> 06:34:52,257
s I THINK THE FDA HAS BEEN

9403
06:34:52,257 --> 06:34:53,091
EXTREMELY GOOD.

9404
06:34:53,091 --> 06:34:55,193
I REALLY HAVE TO SIT HERE AND

9405
06:34:55,193 --> 06:34:58,263
SAY THAT THE FDA HAS DONE IT THE

9406
06:34:58,263 --> 06:35:01,967
RIGHT WAY EVERY SINGLE STEP.

9407
06:35:01,967 --> 06:35:03,935
THEY ALWAYS HAVE HAD PATIENT --

9408
06:35:03,935 --> 06:35:05,136
YOU KNOW, PATIENT WELL-BEING IN

9409
06:35:05,136 --> 06:35:07,739
FRONT OF THEM.

9410
06:35:07,739 --> 06:35:09,941
SO I THINK THAT, YOU KNOW, IS

9411
06:35:09,941 --> 06:35:11,610
THIS BLACK BOX WHEN YOU FIRST

9412
06:35:11,610 --> 06:35:13,078
START INTERACTING WITH THE FDA?

9413
06:35:13,078 --> 06:35:14,579
OF COURSE WE INTERACTED WITH

9414
06:35:14,579 --> 06:35:16,281
THEM A LOT WITH A LOT OF OUR

9415
06:35:16,281 --> 06:35:17,582
TECHNOLOGIES OVER THE YEARS.

9416
06:35:17,582 --> 06:35:18,950
THEY WERE ALWAYS HELPFUL.

9417
06:35:18,950 --> 06:35:21,853
THEY ALWAYS WANT YOU TO SUCCEED.

9418
06:35:21,853 --> 06:35:23,588
YOU HAVE TO GO IN KNOWING THE

9419
06:35:23,588 --> 06:35:24,489
RIGHT QUESTIONS.

9420
06:35:24,489 --> 06:35:26,791
I THINK THE NUMBER ONE CHALLENGE

9421
06:35:26,791 --> 06:35:28,260
IS KNOWING WHAT YOUR QUESTION

9422
06:35:28,260 --> 06:35:30,729
NEEDS TO BE, THAT YOU NEED TO

9423
06:35:30,729 --> 06:35:31,363
ANSWER.

9424
06:35:31,363 --> 06:35:34,532
AND THAT YOU'RE WELL PREPARED

9425
06:35:34,532 --> 06:35:35,834
WITH THE SCIENCE AND RELEASE

9426
06:35:35,834 --> 06:35:36,735
CRITERIA FOR TECHNOLOGIES BEFORE

9427
06:35:36,735 --> 06:35:38,970
YOU TAKE THEM THERE SO YOU DON'T

9428
06:35:38,970 --> 06:35:40,805
HAVE TO REINVENT THE WHEEL AND

9429
06:35:40,805 --> 06:35:41,106
FAIL.

9430
06:35:41,106 --> 06:35:42,641
SO TALK TO THEM EARLY.

9431
06:35:42,641 --> 06:35:43,842
TALK TO THEM OFTEN.

9432
06:35:43,842 --> 06:35:45,277
INTERACT WITH THEM.

9433
06:35:45,277 --> 06:35:46,077
THAT'S MY ADVICE.

9434
06:35:46,077 --> 06:35:48,046
THEY HAVE BEEN A GREAT PARTNER

9435
06:35:48,046 --> 06:35:51,049
AND GREAT RESOURCE FOR US.

9436
06:35:51,049 --> 06:35:53,685
 

9437
06:35:53,685 --> 06:35:57,122
>> GREAT.

9438
06:35:57,122 --> 06:35:59,491
LET ME THANK YOU FOR THE GREAT

9439
06:35:59,491 --> 06:35:59,724
TALKS.

9440
06:35:59,724 --> 06:36:01,893
>> WE'LL TAKE A 15-MINUTE
BREAK

9441
06:36:01,893 --> 06:36:05,297
AND START AT 4:00, GO TO 4:30 AT

9442
06:36:05,297 --> 06:36:05,730
PLANNED.

9443
06:36:05,730 --> 06:36:07,132
I THINK WE'VE COVERED A LOT OF

9444
06:36:07,132 --> 06:36:09,734
WHAT WE WANTED TO GET OUT OF THE

9445
06:36:09,734 --> 06:36:13,838
NEXT SESSION, WHICH IS A SUMMARY

9446
06:36:13,838 --> 06:36:17,442
OF BRINK THE TOPICS TOGETHER

9447
06:36:17,442 --> 06:36:18,777
INTO FOCUS, WE'LL SPEND 30

9448
06:36:18,777 --> 06:36:32,368
MINUTES ON THAT STARTING AT
4:00.

9449
06:36:32,368 --> 06:36:35,137
SO WHEN EVERYBODY IS
READY.

9450
06:36:35,137 --> 06:36:38,240
I THINK WHAT I WILL DO IS SORT

9451
06:36:38,240 --> 06:36:40,543
OF GO OVER WHAT THE AIM, WHAT

9452
06:36:40,543 --> 06:36:42,178
THE PURPOSE OF THIS WAS.

9453
06:36:42,178 --> 06:36:46,549
AND THEN TURN IT OVER TO JOHNNY

9454
06:36:46,549 --> 06:36:47,283
TO MODERATE.

9455
06:36:47,283 --> 06:36:50,352
SO, WHAT WE -- THE WAY WE

9456
06:36:50,352 --> 06:36:51,353
PLANNED THESE COUPLE SESSIONS,

9457
06:36:51,353 --> 06:36:53,055
THE ONE THIS AFTERNOON AND THEN

9458
06:36:53,055 --> 06:36:54,990
TOMORROW MORNING, WAS TO TAKE

9459
06:36:54,990 --> 06:36:56,592
TWO TOPICS THAT WE THOUGHT WOULD

9460
06:36:56,592 --> 06:37:01,397
BE SORT OF THE PLATFORMS THAT

9461
06:37:01,397 --> 06:37:02,731
MIGHT APPROPRIATE FOR CELL-BASED

9462
06:37:02,731 --> 06:37:04,366
THERAPIES CONSORTIUM.

9463
06:37:04,366 --> 06:37:05,601
WE'VE HEARD ABOUT DIFFERENT

9464
06:37:05,601 --> 06:37:07,303
POSSIBILITIES AND INCLUDING SUCH

9465
06:37:07,303 --> 06:37:10,172
THINGS AS ORGANOIDS AND

9466
06:37:10,172 --> 06:37:10,806
EXTRACELLULAR VESICLES.

9467
06:37:10,806 --> 06:37:14,543
BUT A LITTLE HARDER TO GET

9468
06:37:14,543 --> 06:37:16,512
ALIGNMENT ON THOSE, WHO AREAS WE

9469
06:37:16,512 --> 06:37:19,949
COULD LIKELY GET ALIGNMENT BOTH

9470
06:37:19,949 --> 06:37:27,156
ACROSS NIH INSTITUTES, FEDERAL 

9471
06:37:27,156 --> 06:37:36,765
AGENCIES WITH PRIEF SECTORS,

9472
06:37:36,765 --> 06:37:38,167
REGENERATIVE MEDICINE AND

9473
06:37:38,167 --> 06:37:39,268
iPSCs, COALESCE AND DRAW

9474
06:37:39,268 --> 06:37:41,604
BOUNDARY THAT COULD BE REFINED,

9475
06:37:41,604 --> 06:37:44,673
AND PERHAPS BY GROUPS OF

9476
06:37:44,673 --> 06:37:45,875
INTERNAL GROUP, TAKEN TO

9477
06:37:45,875 --> 06:37:47,810
INDUSTRY FOR INPUT WHAT THEY

9478
06:37:47,810 --> 06:37:50,446
MIGHT BE INTERESTED IN,

9479
06:37:50,446 --> 06:37:52,248
INCLUDING SUCH THINGS AS

9480
06:37:52,248 --> 06:37:53,749
POSSIBLE TRIALS.

9481
06:37:53,749 --> 06:37:57,686
SO, THIS SESSION WE HAD TODAY WE

9482
06:37:57,686 --> 06:37:59,555
HEARD FANTASTIC TALKS, EXCITING

9483
06:37:59,555 --> 06:38:01,190
THINGS, SHOWING POTENTIAL OF

9484
06:38:01,190 --> 06:38:04,159
WHAT REGENERATIVE MEDICINE COULD

9485
06:38:04,159 --> 06:38:04,460
BE.

9486
06:38:04,460 --> 06:38:08,330
BUT IT WASN'T QUITE ON TOPIC.

9487
06:38:08,330 --> 06:38:11,267
IT WASN'T QUITE ON STEM CELLS.

9488
06:38:11,267 --> 06:38:12,668
IT WAS BROADER THAN THAT.

9489
06:38:12,668 --> 06:38:14,536
WE HEARD A LOT OF INTERESTING

9490
06:38:14,536 --> 06:38:16,739
THINGS, BUT WHAT WE WANT TO DO

9491
06:38:16,739 --> 06:38:20,576
IN THIS SESSION NOW IS TO TAKE

9492
06:38:20,576 --> 06:38:22,778
THE FOCUS OF TISSUE-SPECIFIC

9493
06:38:22,778 --> 06:38:25,514
STEM CELLS AND THINK ABOUT WHAT

9494
06:38:25,514 --> 06:38:29,985
IS A SORT OF FOCUS, AN AREA OF

9495
06:38:29,985 --> 06:38:32,721
RESEARCH, THAT COULD BE DONE AS

9496
06:38:32,721 --> 06:38:33,589
CONSORTIUM THAT WOULD PRODUCE

9497
06:38:33,589 --> 06:38:36,425
DATA THAT WOULD BE OF INTEREST

9498
06:38:36,425 --> 06:38:38,394
BOTH TO US AS RESEARCHERS AND

9499
06:38:38,394 --> 06:38:41,463
INDIVIDUAL LABS AND NIH FUNDERS

9500
06:38:41,463 --> 06:38:44,099
AND TO NIH.

9501
06:38:44,099 --> 06:38:46,635
WITHIN THAT SPHERE OF TISSUE

9502
06:38:46,635 --> 06:38:48,170
CELLS, TISSUE-SPECIFIC STEM

9503
06:38:48,170 --> 06:38:48,370
CELLS.

9504
06:38:48,370 --> 06:38:50,339
AND JOHNNY AND I DISCUSSED A

9505
06:38:50,339 --> 06:38:51,774
COUPLE IDEAS, BUT THE POINT HERE

9506
06:38:51,774 --> 06:38:54,276
IS THIS IS NOT NIH TALKING TO

9507
06:38:54,276 --> 06:38:55,544
YOU ALL AND TELLING US WHAT WE

9508
06:38:55,544 --> 06:38:56,345
WANT TO DO.

9509
06:38:56,345 --> 06:38:58,647
THIS IS YOUR CHANCE FOR YOU ALL

9510
06:38:58,647 --> 06:39:02,251
TO DEFINE THIS SORT OF

9511
06:39:02,251 --> 06:39:02,885
CONSORTIUM-TYPE PROJECT.

9512
06:39:02,885 --> 06:39:04,653
WE WANT TO SEE HOW YOU DEVELOP

9513
06:39:04,653 --> 06:39:07,323
IT, WHAT ARE YOUR IDEAS. 

9514
06:39:07,323 --> 06:39:09,925
WITH THAT, JOHNNY?

9515
06:39:09,925 --> 06:39:13,295
 

9516
06:39:13,295 --> 06:39:15,497
>> YES, I THINK, YOU KNOW,
WHAT

9517
06:39:15,497 --> 06:39:17,166
WE HEARD ABOUT, A LOT OF

9518
06:39:17,166 --> 06:39:18,667
DIFFERENT THINGS.

9519
06:39:18,667 --> 06:39:21,837
WE LEARNED ABOUT iPS CELLS,

9520
06:39:21,837 --> 06:39:23,605
SMART STEM CELLS,

9521
06:39:23,605 --> 06:39:26,775
TISSUE-SPECIFIC STEM CELLS,

9522
06:39:26,775 --> 06:39:28,110
FULLY DIFFERENTIATED CELLS.

9523
06:39:28,110 --> 06:39:31,814
AND ONE THING I TRIED TO GATHER,

9524
06:39:31,814 --> 06:39:33,682
YOU KNOW, CROSS-CUTTING RESEARCH

9525
06:39:33,682 --> 06:39:34,316
NEEDS, AN EXAMPLE.

9526
06:39:34,316 --> 06:39:42,391
AS PART OF THE RMIP PROJECT, THE

9527
06:39:42,391 --> 06:39:45,494
CATALYST PROGRAM ALLOWS YOU LIKE

9528
06:39:45,494 --> 06:39:47,796
ME IN VAIL, CANNOT DO PROTEIN OR

9529
06:39:47,796 --> 06:39:50,099
RNAseq, I SEND THE CELLS TO

9530
06:39:50,099 --> 06:39:52,401
THEM, THEY DO ANALYSIS, THAT'S

9531
06:39:52,401 --> 06:39:54,570
ONE AREA THAT I THINK IF WE WERE

9532
06:39:54,570 --> 06:39:59,074
ALL DOING THIS THEN WE WOULD

9533
06:39:59,074 --> 06:40:01,143
KNOW WHICH WE'RE TALKING ABOUT.

9534
06:40:01,143 --> 06:40:02,544
I WANT TO TELL YOU IN THE

9535
06:40:02,544 --> 06:40:05,314
CLINICAL TRIALS I TALKED ABOUT

9536
06:40:05,314 --> 06:40:06,615
THIS MORNING, WE HAVE VERY FEW

9537
06:40:06,615 --> 06:40:09,118
STEM CELLS IN THE BONE MARROW

9538
06:40:09,118 --> 06:40:09,885
WE'VE INJECTED.

9539
06:40:09,885 --> 06:40:11,086
WE'RE TALKING ABOUT THOUSANDS OF

9540
06:40:11,086 --> 06:40:12,187
STEM CELLS.

9541
06:40:12,187 --> 06:40:14,590
THAT IS VERY IMPORTANT BECAUSE

9542
06:40:14,590 --> 06:40:18,260
WHEN I TALKED TO CHRIS, SEND ME

9543
06:40:18,260 --> 06:40:20,295
THE CELLS IN GEORGIA TECH OR

9544
06:40:20,295 --> 06:40:22,064
WHEREVER, I DON'T HAVE A LOT OF

9545
06:40:22,064 --> 06:40:22,431
CELLS.

9546
06:40:22,431 --> 06:40:23,999
I DON'T WANT TO GIVE IT TO YOU

9547
06:40:23,999 --> 06:40:29,071
BECAUSE I NEED IT BECAUSE NOW I

9548
06:40:29,071 --> 06:40:33,542
FEEL THE EXOSOME IS PROBABLY

9549
06:40:33,542 --> 06:40:33,909
VERY IMPORTANT.

9550
06:40:33,909 --> 06:40:37,613
I FOUND THOUSAND OF STEM CELLS

9551
06:40:37,613 --> 06:40:44,586
IN BONE MARROW, BILLIONS IN THE

9552
06:40:44,586 --> 06:40:44,820
EXOSOME.

9553
06:40:44,820 --> 06:40:46,789
ONE AREA TO DISCUSS AFTER THAT

9554
06:40:46,789 --> 06:40:50,059
IS THE FACT THAT WE TALKED A LOT

9555
06:40:50,059 --> 06:40:51,927
TODAY ABOUT IF I GROW THE STEM

9556
06:40:51,927 --> 06:40:54,430
CELLS ARE THEY AS POTENT BEFORE

9557
06:40:54,430 --> 06:41:00,569
STARTING TO DO THE EXPANSION AND

9558
06:41:00,569 --> 06:41:01,670
WITHOUT CLONAL ANALYSIS, I'VE

9559
06:41:01,670 --> 06:41:05,574
BEEN DOING CELLS A LONG TIME.

9560
06:41:05,574 --> 06:41:08,844
ONE THING IF YOU LOOK AT A

9561
06:41:08,844 --> 06:41:17,186
PATIENT, WHAT DO YOU DO, THE

9562
06:41:17,186 --> 06:41:18,954
STEM CELLS, EXPANDED, FULL BODY

9563
06:41:18,954 --> 06:41:23,092
RADIATION TO THE PATIENT, AND

9564
06:41:23,092 --> 06:41:25,828
AFTER THIS REINJECT

9565
06:41:25,828 --> 06:41:27,029
HEMATOPOIETIC STEM CELLS BANKED

9566
06:41:27,029 --> 06:41:29,565
TWO WEEKS BEFORE, THEY DON'T DO

9567
06:41:29,565 --> 06:41:30,532
AN EXPANSION.

9568
06:41:30,532 --> 06:41:32,401
THEY SAVE LIFE EVERY SINGLE DAY

9569
06:41:32,401 --> 06:41:34,369
WITH THIS TREATMENT SOAP THE

9570
06:41:34,369 --> 06:41:35,671
QUESTION THAT I -- SO THE

9571
06:41:35,671 --> 06:41:37,639
QUESTION I WOULD LIKE TO ASK THE

9572
06:41:37,639 --> 06:41:39,641
GROUP FOR SOME APPLICATION DO WE

9573
06:41:39,641 --> 06:41:43,278
NEED BILLIONS OF STEM CELLS?

9574
06:41:43,278 --> 06:41:45,547
IF THEY CAN RECONSTITUTE LITERS

9575
06:41:45,547 --> 06:41:47,182
OF BONE MARROW WITH A FEW

9576
06:41:47,182 --> 06:41:50,586
HEMATOPOIETIC STEM CELLS, WHY WE

9577
06:41:50,586 --> 06:41:51,854
CANNOT USE THEM TO INJECT INTO

9578
06:41:51,854 --> 06:41:55,824
THE KNEE JOINT OF THE PATIENT,

9579
06:41:55,824 --> 06:41:57,426
AND THE INJECTION, ONE THING I

9580
06:41:57,426 --> 06:41:59,194
KNOW, I DON'T KNOW IF IT'S

9581
06:41:59,194 --> 06:41:59,862
WORKING BECAUSE THE CLINICAL

9582
06:41:59,862 --> 06:42:02,164
TRIALS IS ON THEIR WAY NOW, WE

9583
06:42:02,164 --> 06:42:03,599
HAVE THE PLACEBO GLOBE, DOING

9584
06:42:03,599 --> 06:42:06,001
ALL THIS WORK, I CAN TELL YOU

9585
06:42:06,001 --> 06:42:10,739
SOMETHING, THERE IS NOT A LOT OF

9586
06:42:10,739 --> 06:42:12,641
STEM CELL TO START WITH AND

9587
06:42:12,641 --> 06:42:13,876
THOSE PATIENTS ARE GETTING

9588
06:42:13,876 --> 06:42:14,176
OLDER.

9589
06:42:14,176 --> 06:42:16,211
CLEARLY I THINK IS THERE A PLACE

9590
06:42:16,211 --> 06:42:19,248
SOMEWHERE, WHERE WE CAN TALK

9591
06:42:19,248 --> 06:42:20,349
ABOUT NOT EXPANDING THOSE STEM

9592
06:42:20,349 --> 06:42:22,117
CELLS, DO WE HAVE ANY

9593
06:42:22,117 --> 06:42:23,519
APPLICATION TO THINK OF, AND CAN

9594
06:42:23,519 --> 06:42:24,953
WE START TO COLLABORATE ON

9595
06:42:24,953 --> 06:42:26,188
SOMETHING LIKE THIS, OR MAYBE

9596
06:42:26,188 --> 06:42:28,657
IT'S A CRAZY IDEA BUT I REALLY

9597
06:42:28,657 --> 06:42:30,058
BELIEVE THIS IS SOMETHING WE

9598
06:42:30,058 --> 06:42:33,262
NEED TO PAY ATTENTION BECAUSE

9599
06:42:33,262 --> 06:42:39,735
FACE IT, IF YOU PUT THEM IN

9600
06:42:39,735 --> 06:42:42,871
PETRI DISHES, REMOVE THEM, CELLS

9601
06:42:42,871 --> 06:42:48,844
BECOME SENESCENT, NOW WE HAVE

9602
06:42:48,844 --> 06:42:51,146
PAPER SHOWN CLEARLY, WHEN YOU

9603
06:42:51,146 --> 06:42:52,915
GROW THEM, WE KNOW THE GROWING

9604
06:42:52,915 --> 06:42:55,551
THE STEM CELLS HAS A NEGATIVE

9605
06:42:55,551 --> 06:42:58,287
IMPACT ON THEIR FUNCTION.

9606
06:42:58,287 --> 06:43:00,122
THAT HAS BEEN PUBLISHED FOR MANY

9607
06:43:00,122 --> 06:43:00,355
YEARS.

9608
06:43:00,355 --> 06:43:02,624
WOULD LIKE TO OPEN UP WITH THIS

9609
06:43:02,624 --> 06:43:04,293
IF THERE'S ANY COMMENTS TO THIS.

9610
06:43:04,293 --> 06:43:12,734
I'M SURE THERE IS A LOT. 

9611
06:43:12,734 --> 06:43:15,137
>> YOUR TALK WAS STRIKING
YOU'RE

9612
06:43:15,137 --> 06:43:16,305
MAKING CARTILAGE THE SAME WAY

9613
06:43:16,305 --> 06:43:19,374
I'M MAKING A BLOOD VESSEL, USING

9614
06:43:19,374 --> 06:43:23,745
BONE MARROW MONO NUCLEAR CELLS,

9615
06:43:23,745 --> 06:43:25,180
YOU'RE USING DERIVED CELLS,

9616
06:43:25,180 --> 06:43:26,215
WE'RE CREATING TISSUES.

9617
06:43:26,215 --> 06:43:28,917
I TOO DID THE BACK OF THE NAPKIN

9618
06:43:28,917 --> 06:43:32,688
CALCULATION, SAW VERY FEW STEM

9619
06:43:32,688 --> 06:43:34,823
CELLS AND THEN SHOWED THE SEEDED

9620
06:43:34,823 --> 06:43:36,558
CELLS PLAY NO ROLE IN TISSUE

9621
06:43:36,558 --> 06:43:38,860
FORMATION.

9622
06:43:38,860 --> 06:43:39,394
I.

9623
06:43:39,394 --> 06:43:41,263
I THINK IT GOES BACK TO THE

9624
06:43:41,263 --> 06:43:42,798
NOTION OF STEM CELLS, BASICALLY

9625
06:43:42,798 --> 06:43:44,833
A CONCEPT THAT WAS DEVELOPED AS

9626
06:43:44,833 --> 06:43:45,968
PART OF DEVELOPMENTAL BIOLOGY.

9627
06:43:45,968 --> 06:43:48,503
I THINK WE'RE TALKING ABOUT

9628
06:43:48,503 --> 06:43:50,239
REGENERATIVE MEDICINE, WITH THE

9629
06:43:50,239 --> 06:43:52,307
SORT OF THERAPIES DISCUSSED

9630
06:43:52,307 --> 06:43:54,476
TODAY, WE'RE NOT TRYING TO MIMIC

9631
06:43:54,476 --> 06:43:55,277
DEVELOPMENTAL PATHWAY.

9632
06:43:55,277 --> 06:43:57,145
I THINK THERE'S VALUE IN

9633
06:43:57,145 --> 06:43:57,479
STUDYING THAT.

9634
06:43:57,479 --> 06:43:58,447
WE'VE LEARNED A LOT OF THINGS.

9635
06:43:58,447 --> 06:44:01,383
WHAT WE'RE TRYING TO DO IS

9636
06:44:01,383 --> 06:44:02,217
REGENERATE.

9637
06:44:02,217 --> 06:44:04,786
IF YOU THINK ABOUT REGENERATION

9638
06:44:04,786 --> 06:44:05,454
FROM THE EVOLUTIONARY

9639
06:44:05,454 --> 06:44:07,189
PERSPECTIVE WE HAVE THE ABILITY

9640
06:44:07,189 --> 06:44:09,057
TO REGENERATE AND LOST A LOT OF

9641
06:44:09,057 --> 06:44:09,424
IT.

9642
06:44:09,424 --> 06:44:11,560
WE STILL POSSESS SOME BUT WHAT'S

9643
06:44:11,560 --> 06:44:14,196
STRIKING IS WHEN YOU LOOK AT

9644
06:44:14,196 --> 06:44:16,131
ANIMALS THAT CAN REGENERATE,

9645
06:44:16,131 --> 06:44:18,300
IT'S INFLAMMATION MEDIATED

9646
06:44:18,300 --> 06:44:18,533
PROCESS.

9647
06:44:18,533 --> 06:44:19,901
I THINK INFLAMMATION, ITS ROLE

9648
06:44:19,901 --> 06:44:21,503
IN REGENERATION IS SOMETHING

9649
06:44:21,503 --> 06:44:22,371
THAT NEEDS MORE ATTENTION.

9650
06:44:22,371 --> 06:44:25,574
>> I WOULD SAY
INFLAMMATION AND

9651
06:44:25,574 --> 06:44:27,209
FIBROSIS BECAUSE FIBROSIS IS

9652
06:44:27,209 --> 06:44:28,243
ALSO, YOU KNOW, AS TONY WAS

9653
06:44:28,243 --> 06:44:30,646
SAYING, ONE OF THE BIGGEST

9654
06:44:30,646 --> 06:44:31,980
ENEMIES FOR TISSUE REPAIR.

9655
06:44:31,980 --> 06:44:37,719
AND THIS IS WHY WE'RE USING

9656
06:44:37,719 --> 06:44:38,086
(INDISCERNIBLE).

9657
06:44:38,086 --> 06:44:39,388
IS THERE ANY -- YOU KNOW, PEOPLE

9658
06:44:39,388 --> 06:44:42,457
IN THE ROOM THAT DO SOME

9659
06:44:42,457 --> 06:44:44,226
INJECTION OF NON-EXPANDED STEM

9660
06:44:44,226 --> 06:44:50,332
CELLS? 

9661
06:44:50,332 --> 06:44:50,465
 

9662
06:44:50,465 --> 06:44:53,835
>> IS THERE NEIGHBOR DO AN

9663
06:44:53,835 --> 06:44:54,836
INJECTION OF NON-EXPANDED STEM

9664
06:44:54,836 --> 06:44:57,172
CELL THAT HAS NOT BEEN EXPANDED.

9665
06:44:57,172 --> 06:45:02,678
>> SO, YEAH, WE HAVE A
CLINICAL

9666
06:45:02,678 --> 06:45:07,049
TRIAL, WE'RE DOING BONE MARROW

9667
06:45:07,049 --> 06:45:09,484
AND REINJECTING BACK INTO THE

9668
06:45:09,484 --> 06:45:11,353
HEART, INJECTED 130 PATIENTS,

9669
06:45:11,353 --> 06:45:12,454
RESULTS ARE NOT FINISHED YET.

9670
06:45:12,454 --> 06:45:14,089
WE HAVE THOSE.

9671
06:45:14,089 --> 06:45:20,295
WE DO KEEP SOME CELL PRODUCT, IT

9672
06:45:20,295 --> 06:45:24,166
HAS A UNIQUE SPIN TO IT THAT

9673
06:45:24,166 --> 06:45:25,467
WE'RE TAKING POTENCY-SELECTED

9674
06:45:25,467 --> 06:45:28,737
PRODUCTS, SO WE ACTUALLY DO A

9675
06:45:28,737 --> 06:45:30,105
SMALL VOLUME BONE MARROW

9676
06:45:30,105 --> 06:45:31,473
ASPIRATE IT THE PATIENT, TWO

9677
06:45:31,473 --> 06:45:34,309
WEEKS PRIOR TO THE ACTUAL

9678
06:45:34,309 --> 06:45:35,544
TREATMENT TO DETERMINE WHETHER

9679
06:45:35,544 --> 06:45:37,379
THEY MEET CERTAIN POTENCY

9680
06:45:37,379 --> 06:45:38,246
REQUIREMENTS.

9681
06:45:38,246 --> 06:45:39,915
IF THEY DO, THEY WILL COME BACK,

9682
06:45:39,915 --> 06:45:41,783
INVITED BACK TWO WEEKS LATER, DO

9683
06:45:41,783 --> 06:45:44,119
A MUCH LARGER VOLUME BONE MARROW

9684
06:45:44,119 --> 06:45:45,721
ASPIRATE AND REINJECT BACK INTO

9685
06:45:45,721 --> 06:45:47,589
THE HEART, SO THAT'S BEEN GOING

9686
06:45:47,589 --> 06:45:48,056
ON.

9687
06:45:48,056 --> 06:45:49,691
SIMILAR TRIALS LIKE THAT IN

9688
06:45:49,691 --> 06:45:50,659
CARDIOLOGY HAVE BEEN DONE

9689
06:45:50,659 --> 06:45:53,161
BEFORE.

9690
06:45:53,161 --> 06:46:02,137
 

9691
06:46:02,137 --> 06:46:04,940
>> ALKALINE BURN IN ONE
EYE,

9692
06:46:04,940 --> 06:46:08,744
STANDARD CARE TO TRANSPLANT IN

9693
06:46:08,744 --> 06:46:10,645
BOTH EYE, NO EXPANSION.

9694
06:46:10,645 --> 06:46:12,447
>> I KNEW THERE IS
APPLICATION

9695
06:46:12,447 --> 06:46:16,718
WE CANNOT DO IT LIKE THE  IPS

9696
06:46:16,718 --> 06:46:18,920
CELL BUT FOR SOME MAYBE WE NEED

9697
06:46:18,920 --> 06:46:21,490
TO LOOK INTO THIS.

9698
06:46:21,490 --> 06:46:23,725
>> SO, I HAVE TO TAKE A
LITTLE

9699
06:46:23,725 --> 06:46:26,661
BIT OF ISSUE WITH SUCH AN

9700
06:46:26,661 --> 06:46:30,098
INTENSE FOCUS ON STEM CELLS

9701
06:46:30,098 --> 06:46:34,236
BECAUSE THE RMIP PROJECT INDEED

9702
06:46:34,236 --> 06:46:37,038
WAS DICTATED BY CONGRESSIONAL

9703
06:46:37,038 --> 06:46:37,706
MANDATE REQUIRING CLINICAL FOCUS

9704
06:46:37,706 --> 06:46:39,141
USING STEM CELLS.

9705
06:46:39,141 --> 06:46:40,242
THAT WAS A CONGRESSIONAL

9706
06:46:40,242 --> 06:46:40,475
MANDATE.

9707
06:46:40,475 --> 06:46:44,179
BUT THAT DOES NOT MEAN THAT THAT

9708
06:46:44,179 --> 06:46:46,047
DEFINES REGENERATIVE MEDICINE.

9709
06:46:46,047 --> 06:46:48,049
AND SO I THINK IT'S PROBABLY A

9710
06:46:48,049 --> 06:46:52,788
MISTAKE TO PUT SO MUCH FOCUS ON

9711
06:46:52,788 --> 06:46:54,890
SOME SORT OF -- IF YOU WANT TO

9712
06:46:54,890 --> 06:46:57,859
CALL EIGHT STEM CELL, PRECURSOR

9713
06:46:57,859 --> 06:46:58,493
CELL, REGENERATIVE CELL,

9714
06:46:58,493 --> 06:47:00,462
WHATEVER YOU WANT TO CALL IT BUT

9715
06:47:00,462 --> 06:47:06,902
HAVING AN  INTENSE FOCUS ON CELL

9716
06:47:06,902 --> 06:47:08,503
BIOLOGY TAKES US AWAY FROM THE

9717
06:47:08,503 --> 06:47:13,208
FACT THERE'S A LOT OF NIH MONEY

9718
06:47:13,208 --> 06:47:14,943
GOING INTO CELL BIOLOGY, NOT AS

9719
06:47:14,943 --> 06:47:16,144
MUCH INTO UNDERSTANDING HOW

9720
06:47:16,144 --> 06:47:17,446
CELLS COME TOGETHER AND MAKE A

9721
06:47:17,446 --> 06:47:18,880
TISSUE OR ORGAN WHICH IS

9722
06:47:18,880 --> 06:47:21,950
ACTUALLY WHAT WE'RE GOING AFTER,

9723
06:47:21,950 --> 06:47:22,451
RIGHT?

9724
06:47:22,451 --> 06:47:28,190
SO, I THINK TOO MUCH EMPHASIS ON

9725
06:47:28,190 --> 06:47:29,724
THE CELL, PER SE, EVENING THOUGH

9726
06:47:29,724 --> 06:47:31,393
THAT'S THE FUNCTIONAL UNIT

9727
06:47:31,393 --> 06:47:32,561
IGNORES THE FACT THE CELL HAS TO

9728
06:47:32,561 --> 06:47:35,831
BE IN AN ENVIRONMENT.

9729
06:47:35,831 --> 06:47:36,932
WE TALKED ABOUT FIBROSIS, WE

9730
06:47:36,932 --> 06:47:39,167
DON'T KNOW MUCH ABOUT HOW WE GET

9731
06:47:39,167 --> 06:47:40,469
PAST THE SCARRING ENVIRONMENT.

9732
06:47:40,469 --> 06:47:42,671
BEYOND EVEN JUST THAT FIBROTIC

9733
06:47:42,671 --> 06:47:45,140
AND SCARRING ENVIRONMENT THERE'S

9734
06:47:45,140 --> 06:47:46,641
A TISSUE MILIEU WHICH SOMETIMES

9735
06:47:46,641 --> 06:47:47,909
THERE ARE ACTUALLY THINGS THAT

9736
06:47:47,909 --> 06:47:50,045
ARE GOING VERY CLOSE TO THE

9737
06:47:50,045 --> 06:47:51,646
CLINIC NOW THAT ARE IN CLINICAL

9738
06:47:51,646 --> 06:47:55,717
TRIALS WHERE THERE'S NO CELLS AT

9739
06:47:55,717 --> 06:47:56,885
ALL.

9740
06:47:56,885 --> 06:47:57,786
IT'S AN EXTRACELLULAR

9741
06:47:57,786 --> 06:48:00,188
MATRIX-BASED PRODUCT OF ONE KIND

9742
06:48:00,188 --> 06:48:02,757
OR ANOTHER, EITHER DECELLED OR

9743
06:48:02,757 --> 06:48:04,793
DE NOVOD OR SOMETHING.

9744
06:48:04,793 --> 06:48:06,328
WHAT WE FIND SURPRISINGLY IN

9745
06:48:06,328 --> 06:48:08,830
SOME CASES IS THAT AFTER TIME,

9746
06:48:08,830 --> 06:48:09,631
THIS THING REMODELS BECAUSE

9747
06:48:09,631 --> 06:48:12,467
CELLS IN THE BODY COME IN AND

9748
06:48:12,467 --> 06:48:14,870
THAT'S -- IT'S JUST REGENERATION

9749
06:48:14,870 --> 06:48:16,304
OCCURS BECAUSE WE PROVIDED THE

9750
06:48:16,304 --> 06:48:17,138
RIGHT ENVIRONMENT.

9751
06:48:17,138 --> 06:48:19,140
SO, I'M NOT SAYING WE SHOULD

9752
06:48:19,140 --> 06:48:21,309
JUST DO THAT, BUT I THINK AT OUR

9753
06:48:21,309 --> 06:48:25,046
PERIL DO WE IGNORE THAT BY

9754
06:48:25,046 --> 06:48:26,481
PUTTING A LASER-LIKE FOCUS ON

9755
06:48:26,481 --> 06:48:34,856
CELLS PER SE. 

9756
06:48:34,856 --> 06:48:39,628
 

9757
06:48:39,628 --> 06:48:41,530
>> SO, TO FOLLOW UP AND

9758
06:48:41,530 --> 06:48:43,198
REINFORCE THAT, THINK ABOUT YOUR

9759
06:48:43,198 --> 06:48:45,667
OWN DATA, THINK ABOUT DATA WE'VE

9760
06:48:45,667 --> 06:48:47,469
HEARD TODAY.

9761
06:48:47,469 --> 06:48:49,571
LET'S USE THE KNEE AND THE

9762
06:48:49,571 --> 06:48:51,206
ARTICULAR CARTILAGE AS AN

9763
06:48:51,206 --> 06:48:51,706
EXAMPLE.

9764
06:48:51,706 --> 06:48:53,975
YOU GO BACK IN, YOU DON'T FIND

9765
06:48:53,975 --> 06:48:56,278
THE DONOR CELLS.

9766
06:48:56,278 --> 06:48:59,414
YOU FIND THE HOST CELLS THAT

9767
06:48:59,414 --> 06:48:59,814
HAVE REGENERATED.

9768
06:48:59,814 --> 06:49:02,584
SO, A BIG PART OF THE QUESTION

9769
06:49:02,584 --> 06:49:05,787
IS WHAT ARE THE CELLS WE'RE

9770
06:49:05,787 --> 06:49:07,422
GIVING ACTUALLY TELLING THE HOST

9771
06:49:07,422 --> 06:49:11,026
CELLS, TO USE THAT TERM, RIGHT?

9772
06:49:11,026 --> 06:49:13,962
AND IT MAY BE -- ENVIRONMENT IS

9773
06:49:13,962 --> 06:49:14,629
EVERYTHING.

9774
06:49:14,629 --> 06:49:17,799
MATRIX IS EVERYTHING, AGREED.

9775
06:49:17,799 --> 06:49:23,638
BUT MAYBE WORKING ON THE

9776
06:49:23,638 --> 06:49:26,341
SECRETOME, THE EVASE IS ONE

9777
06:49:26,341 --> 06:49:28,543
EXAMPLE, A HUGE OPPORTUNITY

9778
06:49:28,543 --> 06:49:29,311
HERE.

9779
06:49:29,311 --> 06:49:31,913
THIS WOULD POTENTIALLY SIMPLIFY

9780
06:49:31,913 --> 06:49:33,949
LOGISTICS, EASIER TO UNDERSTAND

9781
06:49:33,949 --> 06:49:36,952
SECRETOME AND PERHAPS MIMIC THE

9782
06:49:36,952 --> 06:49:38,253
SECRETOME, IT'S ANOTHER THING TO

9783
06:49:38,253 --> 06:49:39,487
TAKE ALL THE MANUFACTURING

9784
06:49:39,487 --> 06:49:41,323
LESSONS FOR THE CELLS AND APPLY

9785
06:49:41,323 --> 06:49:44,192
THEM TO PRODUCTION OF EVS.

9786
06:49:44,192 --> 06:49:47,028
THAT'S BOTH AN OPPORTUNITY AND

9787
06:49:47,028 --> 06:49:47,762
NIGHTMARE ACTUALLY.

9788
06:49:47,762 --> 06:49:50,098
BUT, AGAIN, I THINK AS WE THINK

9789
06:49:50,098 --> 06:49:51,866
FURTHER, THIS COULD BE A WAY TO

9790
06:49:51,866 --> 06:49:54,269
GO.

9791
06:49:54,269 --> 06:49:55,036
WITH RESPECT TO THE

9792
06:49:55,036 --> 06:49:56,438
iPS-DERIVED CELLS WE'RE LOOKING

9793
06:49:56,438 --> 06:49:59,708
AT TWO THINGS, RIGHT?

9794
06:49:59,708 --> 06:50:10,085
SO  ENGRAFTMENT VERSUS

9795
06:50:11,252 --> 06:50:12,220
NON-ENGRAFT ITS.

9796
06:50:12,220 --> 06:50:15,790
EPITHELIAL PIG THE OR OTHERWISE,

9797
06:50:15,790 --> 06:50:17,225
HOW MANY REPLICATION OF INJECTED

9798
06:50:17,225 --> 06:50:17,792
CELLS IS THERE?

9799
06:50:17,792 --> 06:50:21,029
OR IS IT A COUPLE CELLS SENDING

9800
06:50:21,029 --> 06:50:24,532
OUT SMOKE SIGNALS TO CAUSE THE

9801
06:50:24,532 --> 06:50:25,967
HOST RETINAL PIGMENT EPITHELIAL

9802
06:50:25,967 --> 06:50:27,068
CELLS TO REPAIR THEMSELVES OR

9803
06:50:27,068 --> 06:50:28,570
WHAT HAVE YOU?

9804
06:50:28,570 --> 06:50:30,705
THAT IS WHERE THE SCIENCE OF

9805
06:50:30,705 --> 06:50:33,008
THIS CONSORTIUM COULD HELP OUT

9806
06:50:33,008 --> 06:50:33,208
WITH.

9807
06:50:33,208 --> 06:50:34,442
>> I TOTALLY AGREE.

9808
06:50:34,442 --> 06:50:38,446
I WANT TO ADD SOMETHING FOR

9809
06:50:38,446 --> 06:50:39,714
CARDIAC REPAIR, THEY SHOWED THE

9810
06:50:39,714 --> 06:50:42,050
REST OF US IF YOU INJECT STEM

9811
06:50:42,050 --> 06:50:47,856
CELLS INTO THE HEART YOU PROMOTE

9812
06:50:47,856 --> 06:50:52,694
CELL CELL REPAIR BUT THEY DO NOT

9813
06:50:52,694 --> 06:50:53,495
BECOME CARDIOMYOCYTE.

9814
06:50:53,495 --> 06:50:55,630
I AGREE A LOT OF US THAT WORK ON

9815
06:50:55,630 --> 06:50:57,599
CARTILAGE REPAIR INJECT INTO THE

9816
06:50:57,599 --> 06:50:59,134
KNEE JOINT, REPAIR CARTILAGE BUT

9817
06:50:59,134 --> 06:51:06,274
WE SEE VERY FEW CELL, IF  ANY,

9818
06:51:06,274 --> 06:51:07,676
INTO THE REPAIR CARTILAGE.

9819
06:51:07,676 --> 06:51:09,310
THE QUESTION COMES UP DO WE NEED

9820
06:51:09,310 --> 06:51:11,746
EXPANDED STEM CELLS TO DO THIS?

9821
06:51:11,746 --> 06:51:13,081
CAN WE USE NON-EXPANDED STEM

9822
06:51:13,081 --> 06:51:16,151
CELLS AND MAYBE THAT'S SOMETHING

9823
06:51:16,151 --> 06:51:16,584
WE CAN THINK ABOUT.

9824
06:51:16,584 --> 06:51:19,387
>> YEAH, I WANT TO COMMENT

9825
06:51:19,387 --> 06:51:22,357
BUILDING ON WHAT WE'VE HEARD, I

9826
06:51:22,357 --> 06:51:25,527
THINK YOU'RE POSING THE QUESTION

9827
06:51:25,527 --> 06:51:27,295
FROM VIEW OF HEMATOPOIETIC STEM

9828
06:51:27,295 --> 06:51:28,496
CELL EXPERT, THAT'S REALLY

9829
06:51:28,496 --> 06:51:28,897
IMPORTANT.

9830
06:51:28,897 --> 06:51:30,699
I WANT TO CONGRATULATE YOU AND

9831
06:51:30,699 --> 06:51:35,370
THE ENTIRE FIELD, FOUNDATIONAL

9832
06:51:35,370 --> 06:51:37,005
WORK IN STEM CELLS, BUT IF YOU

9833
06:51:37,005 --> 06:51:40,542
THINK ABOUT THE HUMAN BODY,

9834
06:51:40,542 --> 06:51:43,144
BLOOD IS ONE OF MANY ORGANS,

9835
06:51:43,144 --> 06:51:45,680
WITH A HUGE CONTRAST BETWEEN

9836
06:51:45,680 --> 06:51:46,981
BLOOD VERSUS A SOLID ORGAN.

9837
06:51:46,981 --> 06:51:49,050
I THINK IN THINKING ABOUT WAYS

9838
06:51:49,050 --> 06:51:51,686
WE COULD RALLY TOGETHER AROUND

9839
06:51:51,686 --> 06:51:53,421
YOUR QUESTION, LET'S TRY CATCH

9840
06:51:53,421 --> 06:51:58,359
UP SOLID ORGAN BIOLOGY TO WHERE

9841
06:51:58,359 --> 06:51:59,894
ARE YOU IN THE BLOOD.

9842
06:51:59,894 --> 06:52:01,730
WE HEARD ABOUT THIS A SECOND

9843
06:52:01,730 --> 06:52:02,697
AGO.

9844
06:52:02,697 --> 06:52:10,038
A HUGE QUESTION OF THE NICHE

9845
06:52:10,038 --> 06:52:13,141
THAT'S MORE PALPABLE, HOW YOU

9846
06:52:13,141 --> 06:52:15,310
CLEAR CELLS IN EACH THESE

9847
06:52:15,310 --> 06:52:22,417
TISSUES, WHAT'S THE ANALOGY OF

9848
06:52:22,417 --> 06:52:23,952
RADIATION, CHEMOTHERAPY FOR

9849
06:52:23,952 --> 06:52:25,587
HEMATOPOIETIC STEM CELL

9850
06:52:25,587 --> 06:52:25,887
TRANSPLANT.

9851
06:52:25,887 --> 06:52:28,857
WE TALK ABOUT A DIFFERENT ORGAN

9852
06:52:28,857 --> 06:52:29,591
WITH NON-HEMATOPOIETIC CELLS, WE

9853
06:52:29,591 --> 06:52:30,959
NEED TO THINK ABOUT THAT

9854
06:52:30,959 --> 06:52:31,459
CONTRAST.

9855
06:52:31,459 --> 06:52:36,531
>> JUST AGAIN TO PUSH BACK
AND 

9856
06:52:36,531 --> 06:52:40,301
CONTINUE WHAT WAS SAID, FOR THIS

9857
06:52:40,301 --> 06:52:44,539
COMMON FOCUS CONSORTIUM FOR

9858
06:52:44,539 --> 06:52:45,607
REGENERATIVE MEDICINE CELL-BASED

9859
06:52:45,607 --> 06:52:47,041
THERAPIES WHAT ARE RELATIVELY

9860
06:52:47,041 --> 06:52:49,544
STABLE TYPES OF VARIABLES IN THE

9861
06:52:49,544 --> 06:52:52,413
REGENERATIVE MEDICINE PROGRAM

9862
06:52:52,413 --> 06:52:55,250
THAT CAN BE QUANTIFIED AND

9863
06:52:55,250 --> 06:52:56,584
UNDERSTOOD ACROSS PLATFORMS?

9864
06:52:56,584 --> 06:52:58,186
AND SO THAT I WOULD ARGUE THAT

9865
06:52:58,186 --> 06:53:02,924
WOULD BE A STABLE CELL TYPE

9866
06:53:02,924 --> 06:53:04,025
LIKE iPS, DIFFERENTIATED CELLS

9867
06:53:04,025 --> 06:53:09,998
UPON WHICH WE CAN LOOK AT

9868
06:53:09,998 --> 06:53:11,666
ENVIRONMENTAL INFLUENCES,

9869
06:53:11,666 --> 06:53:13,067
EXOSOME EFFECTS, TISSUE

9870
06:53:13,067 --> 06:53:14,002
INTERACTION, QUANTIFIED WITH

9871
06:53:14,002 --> 06:53:17,338
MODERN GENOMIC TOOLS AND THEN

9872
06:53:17,338 --> 06:53:18,506
THOSE GENOMIC TOOLS, EPIGENETIC

9873
06:53:18,506 --> 06:53:22,210
TOOLS CAN BE USED ACROSS

9874
06:53:22,210 --> 06:53:26,347
PLATFORMS AND ALSO THEN IS A

9875
06:53:26,347 --> 06:53:28,316
REUSABLE AND PORTABLE SET OF

9876
06:53:28,316 --> 06:53:30,285
INFORMATION TO GO FORWARD,

9877
06:53:30,285 --> 06:53:36,758
WHEREAS SOME OF THE MORE OTHER

9878
06:53:36,758 --> 06:53:38,726
TYPE OF APPROACHES ARE LESS

9879
06:53:38,726 --> 06:53:39,928
DEFINABLE AT LEAST AT CURRENT

9880
06:53:39,928 --> 06:53:41,496
STAGE IN TERMS OF INTERACTION IN

9881
06:53:41,496 --> 06:53:45,500
AND OUT AND CAN BE PORTED ACROSS

9882
06:53:45,500 --> 06:53:45,834
TISSUE TYPES.

9883
06:53:45,834 --> 06:53:48,002
>> YEAH. 

9884
06:53:48,002 --> 06:53:50,772
>> WE HAVE TIME FOR ONE
MORE

9885
06:53:50,772 --> 06:53:51,272
QUESTION OR COMMENT.

9886
06:53:51,272 --> 06:53:53,775
>> RIGHT.

9887
06:53:53,775 --> 06:53:58,146
 

9888
06:53:58,146 --> 06:53:59,581
>> NOT A QUESTION BUT AN
ANSWER

9889
06:53:59,581 --> 06:54:04,485
TO YOUR QUESTION ABOUT THE RPE.

9890
06:54:04,485 --> 06:54:08,756
ENGRAFTMENT OF TRANSPLANTED

9891
06:54:08,756 --> 06:54:10,391
CELLS OCCURS AND SURVIVES FOR

9892
06:54:10,391 --> 06:54:13,661
THE LIFE OF THE ANIMAL.

9893
06:54:13,661 --> 06:54:16,531
THAT'S FOR TRANSPLANT OF RPE

9894
06:54:16,531 --> 06:54:17,031
CELLS.

9895
06:54:17,031 --> 06:54:18,399
THERE'S BEEN TRANSPLANT OF

9896
06:54:18,399 --> 06:54:20,134
NEURAL PROGENITOR CELLS UNDER

9897
06:54:20,134 --> 06:54:22,604
THE RETINA THAT STIMULATES RPE

9898
06:54:22,604 --> 06:54:23,004
PROLIFERATION.

9899
06:54:23,004 --> 06:54:25,640
I THINK BOTH ANSWERS ARE

9900
06:54:25,640 --> 06:54:25,874
CORRECT.

9901
06:54:25,874 --> 06:54:27,475
AND THEN EXOSOMES YOU MENTIONED

9902
06:54:27,475 --> 06:54:30,278
BUT I'LL SKIP OVER AND SAY WE

9903
06:54:30,278 --> 06:54:32,647
MAKE BEADS OF GROWTH FACTORS

9904
06:54:32,647 --> 06:54:36,784
THAT CAN STIMULATE THE RPE.

9905
06:54:36,784 --> 06:54:39,954
THE RPE NICHE IS TIED WITH THE

9906
06:54:39,954 --> 06:54:42,757
BROOKS MEMBRANE ON ONE SIDE,

9907
06:54:42,757 --> 06:54:46,861
PHOTORECEPTORS ON THE OTHER,

9908
06:54:46,861 --> 06:54:49,597
HEXAGONAL, VERY LITTLE

9909
06:54:49,597 --> 06:54:50,398
PROLIFERATION OCCURS NORMALLY

9910
06:54:50,398 --> 06:54:53,201
CAN BE STIMULATED WITH GROWTH

9911
06:54:53,201 --> 06:54:53,701
FACTORS OR PERHAPS WITH

9912
06:54:53,701 --> 06:54:57,272
EXOSOMES, WE HAVEN'T LOOKED AT

9913
06:54:57,272 --> 06:54:57,972
THAT YET.

9914
06:54:57,972 --> 06:55:00,608
BACK TO YOUR QUESTION, INCLUDING

9915
06:55:00,608 --> 06:55:04,045
TISSUE ITSELF, BUT HOW MUCH

9916
06:55:04,045 --> 06:55:05,280
TISSUE REGENERATION HAS NOT

9917
06:55:05,280 --> 06:55:05,813
INVOLVED STEM CELLS?

9918
06:55:05,813 --> 06:55:08,216
I THINK IT WOULD BE VERY LITTLE.

9919
06:55:08,216 --> 06:55:13,354
SO OPENING THE DOOR TO

9920
06:55:13,354 --> 06:55:16,491
REGENERATION MIGHT DRAG STEM

9921
06:55:16,491 --> 06:55:21,829
CELLS OR CELLS ALONG WITH IT.

9922
06:55:21,829 --> 06:55:23,965
>> A REALLY IMPORTANT
STATEMENT

9923
06:55:23,965 --> 06:55:24,766
AND COMMAND.

9924
06:55:24,766 --> 06:55:26,367
THE DEFINITIONS WE'VE ALL THE

9925
06:55:26,367 --> 06:55:28,569
BEEN USING ARE DIFFERENT TODAY.

9926
06:55:28,569 --> 06:55:35,476
AND THAT'S A HUGE PART OF THE

9927
06:55:35,476 --> 06:55:44,385
LACK OF PROBLEM, WE CAN

9928
06:55:44,385 --> 06:55:44,686
ACCELERATE.

9929
06:55:44,686 --> 06:55:47,021
I DEFINE AS ONE THAT CAN

9930
06:55:47,021 --> 06:55:47,989
DIFFERENTIATE INTO AT LEAST ONE

9931
06:55:47,989 --> 06:55:54,595
KIND OF PROJECT  -- PROGENY.

9932
06:55:54,595 --> 06:55:55,697
HOW DO YOU DEFINE?

9933
06:55:55,697 --> 06:55:57,699
>> WE NEED VACATE THE ROOM
VERY

9934
06:55:57,699 --> 06:55:59,734
SHORTLY.

9935
06:55:59,734 --> 06:56:02,236
 

9936
06:56:02,236 --> 06:56:06,507
THE QUICK ANSWER IS
THAT I

9937
06:56:06,507 --> 06:56:10,211
AGREE WITH YOUR DEFINITION OF A

9938
06:56:10,211 --> 06:56:10,912
SELF-RENEWING CELL THAT CAN

9939
06:56:10,912 --> 06:56:15,783
DIFFERENTIATE INTO SOME OTHER 

9940
06:56:15,783 --> 06:56:16,250
TARGET TISSUE.

9941
06:56:16,250 --> 06:56:17,819
HOWEVER WHEN HE USE THE WORD

9942
06:56:17,819 --> 06:56:18,953
STEM CELL SOMETIMES WE'RE

9943
06:56:18,953 --> 06:56:20,488
TALKING ABOUT CELLS THAT WE GET

9944
06:56:20,488 --> 06:56:23,691
OUT OF THE BONE MARROW THAT ARE

9945
06:56:23,691 --> 06:56:24,826
PRECURSOR CELLS FOR

9946
06:56:24,826 --> 06:56:26,127
HEMATOPOIETIC STEM CELLS.

9947
06:56:26,127 --> 06:56:28,730
SOMETIMES WE GET CELLS THAT ARE

9948
06:56:28,730 --> 06:56:29,430
PROFESSIONAL SECRETORY CELLS.

9949
06:56:29,430 --> 06:56:31,866
I DON'T KNOW WHAT TO CALL THEM

9950
06:56:31,866 --> 06:56:34,502
BUT I KNOW IF YOU MAKE A CULTURE

9951
06:56:34,502 --> 06:56:35,837
OF THESE NICE CELLS THAT YOU

9952
06:56:35,837 --> 06:56:37,071
ISOLATE THROUGH SOME KIND OF

9953
06:56:37,071 --> 06:56:41,209
MARKER AND PUT THEM IN CULTURE,

9954
06:56:41,209 --> 06:56:42,810
THEY PEE OUT EXOSOMES LIKE

9955
06:56:42,810 --> 06:56:43,177
CRAZY.

9956
06:56:43,177 --> 06:56:44,512
SO THAT MUST BE THEIR MAJOR

9957
06:56:44,512 --> 06:56:45,713
THING THAT THEY DO.

9958
06:56:45,713 --> 06:56:48,516
ARE THEY THE SAME CELLS THAT ARE

9959
06:56:48,516 --> 06:56:50,284
THOSE PRECURSOR CELLS THAT MAKE

9960
06:56:50,284 --> 06:56:51,152
YOUR TISSUE?

9961
06:56:51,152 --> 06:56:53,087
I WONDER, AND I DOUBT IT

9962
06:56:53,087 --> 06:56:54,122
ACTUALLY, FRANKLY.

9963
06:56:54,122 --> 06:56:55,456
BUT WE DON'T HAVE ENOUGH ASSAYS

9964
06:56:55,456 --> 06:56:57,859
TO SHOW THAT, AT LEAST I HAVEN'T

9965
06:56:57,859 --> 06:57:01,429
SEEN ENOUGH PAPERS TO

9966
06:57:01,429 --> 06:57:06,734
DEMONSTRATE THAT YOU ALWAYS GET

9967
06:57:06,734 --> 06:57:07,602
THAT OUTCOME.

9968
06:57:07,602 --> 06:57:10,638
I AGREE THAT THERE'S A PRECURSOR

9969
06:57:10,638 --> 06:57:13,274
SINGLE-CELL CLONE THAT CAN BE

9970
06:57:13,274 --> 06:57:15,576
PUSHED TO MAKE CERTAIN

9971
06:57:15,576 --> 06:57:16,210
POPULATIONS THAT ARE

9972
06:57:16,210 --> 06:57:17,645
SELF-RENEWABLE BUT ONCE WE PUSH

9973
06:57:17,645 --> 06:57:19,213
TO SOME OTHER THING, ARE THEY

9974
06:57:19,213 --> 06:57:20,281
SOME OTHER THING?

9975
06:57:20,281 --> 06:57:21,682
ARE THEY STILL A STEM CELL?

9976
06:57:21,682 --> 06:57:24,652
I THINK WE THROW THIS TERM

9977
06:57:24,652 --> 06:57:28,256
AROUND SO MUCH WE'RE CONFUSING

9978
06:57:28,256 --> 06:57:29,190
THINGS.

9979
06:57:29,190 --> 06:57:31,626
>> IT'S FUNNY, WHEN WE
WROTE THE

9980
06:57:31,626 --> 06:57:36,464
GRANT I WAS INJECTING BONE 

9981
06:57:36,464 --> 06:57:38,332
MARROW ASPIRATE, I WANTED TO BE

9982
06:57:38,332 --> 06:57:40,401
RESPONSIVE TO THE RFA.

9983
06:57:40,401 --> 06:57:43,871
I HEAR THEY HAD VERY FEW STEM

9984
06:57:43,871 --> 06:57:45,006
CELLS THERE BUT THE QUESTION IN

9985
06:57:45,006 --> 06:57:51,212
THE BACK AND ONE HERE.

9986
06:57:51,212 --> 06:57:55,516
THIS IS OUR LAST
QUESTION.

9987
06:57:55,516 --> 06:58:01,556
 

9988
06:58:01,556 --> 06:58:06,027
 

9989
06:58:06,027 --> 06:58:08,529
ALL THE OF THE MATURE

9990
06:58:08,529 --> 06:58:10,298
LINEAGES, I PUT THAT IN A

9991
06:58:10,298 --> 06:58:13,367
KIDNEY, WHAT DOES THE CELL DO?

9992
06:58:13,367 --> 06:58:14,769
I COULD BE WRONG BUT I DON'T

9993
06:58:14,769 --> 06:58:16,170
THINK ANYBODY HAS EXPLORED THAT.

9994
06:58:16,170 --> 06:58:19,040
IT GETS TO THE HEART AND SOUL OF

9995
06:58:19,040 --> 06:58:21,042
YOUR DEFINITION, BUT WHO CARES.

9996
06:58:21,042 --> 06:58:22,243
IT'S THE APPLICATION, RIGHT?

9997
06:58:22,243 --> 06:58:27,715
AND SO IF I COULD HARVEST A

9998
06:58:27,715 --> 06:58:30,751
WHOLE BUNCH OF SKIN, BASAL

9999
06:58:30,751 --> 06:58:32,286
CELLS, WHATEVER, SERVES AS

10000
06:58:32,286 --> 06:58:33,454
PROGENITOR CELLS IN THE SKIN.

10001
06:58:33,454 --> 06:58:35,223
IF I PUT THOSE INTO A LUNG THEY

10002
06:58:35,223 --> 06:58:38,159
WILL TURN INTO LUNG CELLS,

10003
06:58:38,159 --> 06:58:43,564
THAT'S A GAME CHANGER TYPE
THING.

10004
06:58:43,564 --> 06:58:44,198


10005
06:58:44,198 --> 06:58:45,299
>> [OFF MICROPHONE].

10006
06:58:45,299 --> 06:58:45,967
WELL, TBD, RIGHT?

10007
06:58:45,967 --> 06:58:55,967
THANK YOU, GUYS.