>> YES, THANKING.
THANK YOU VERY MUCH.
SO, WELCOME.
SEEMS LIKE FOREVER SINCE WE'VE
BEEN TOGETHER.
I LOOK FORWARD TO AN IN-PERSON
MEETING, HOPEFULLY SOON.
AS COMMITTEE MEMBERS I WANT TO
REMIND YOU THAT YOU MUST ABSENT
YOURSELF DURING SPECIFIC
DISCUSSIONS WHENEVER YOU'RE
PARTICIPATION AND DELIBERATIONS
OR A PARTICULAR PRODUCT,
PROGRAM, OR ANY OTHER SPECIFIC
MATTER CONSTITUTES A CONFLICT OF
INTEREST, OR CREATES THE
APPEARANCE OF 1.
WE ALL KNOW WHEN WE'RE IN
CONFLICT, SO PLEASE, IT'S REALLY
UP TO YOU TO LET US KNOW IF YOU
FEEL LIKE YOU'RE IN CONFLICT.
IT'S INCUMBENT UPON EACH AND
EVERY 1 OF US TO ADVISE THE
EXECUTIVE SECRETARY
DR. CHRISTOPHER KANE, AND
ABSTAIN FROM WHETHER
PARTICIPATION IN THE DISCUSSION
OR ACTION REGARDING THAT MATTE.
IN KEEPING IN POLICIES GOVERNING
CONFLICT OF INTEREST BASED ON
FINANCIAL HOLDINGS OF SPECIAL
GOVERNMENT EMPLOYEES WHICH
CATEGORY INCLUDES ALL MEMBERS OF
THIS COMMITTEE, WE REALLY MUST
DEPEND ON YOU TO VOLUNTARILY
ABSENT YOURSELF DURING ALL
DISCUSSIONS OF MATTERS THAT
WOULD CONCEIVABLY IMPACT THE
STATUS OF THOSE HOLDINGS AND WE
TRUST YOUR JUDGMENT IN THESE
INSTANCES.
WE ALL ARE VERY MUCH COGNIZANT
OF THESE SORTS OF THINGS SO
PLEASE LET DR. KANE KNOW IF
THERE ARE ANY ISSUES.
MEMBERS OF THE PUBLIC WHO MAY
WISH TO EXPRESS VIEWS REGARDING
ANY ITEMS DISCUSSED DURING
TODAY'S MEETING MAY DO SO BY
WRITING DR. CAIN, THE EXECUTIVE
COMMITTEE WITHIN 10 DAYS AFTER
THE MEETING AND ANY WRITTEN
STATEMENTS BY MEMBERS OF THE
PUBLIC WILL RECEIVE CAREFUL
CONSIDERATION.
BY LAW A QUORUM OF COMMITTEE
MEMBERS IS REQUIRED FOR INSTANCE
IN WHICH A VOTE OCCURS.
DURING TODAY'S MEETING A MINIMUM
OF 8 APPOINTED MEMBERS MUST BE
PRESENT TO VOICE THEIR VOTES
SINCE WE CANNOT PREDICT THE TIME
OR OCCURRENCE OR EMOTION, YOUR
PRESENCE AND A MUST FOR AUGUST
SEGMENT ANDS MEETINGS.
SO CHRIS, DO WE HAVE A QUORUM.
>> WE HAVE ACHIEVED A QUORUM.
>> GREAT.
THANK YOU VERY MUCH.
I NOW--OUR MINUTES ARE ENCLOSED,
HOPEFULLY YOU'VE ALL HAD A
CHANCE TO TAKE A LOOK AT THEM.
ARE THERE ANY CORRECTIONS OR ANY
ISSUES WITH THE MINUTES AND IF
NOT, I WOULD LIKE A MOTION TO
APPROVE THE MINUTES OF THE
OCTOBER 19th 2023 MEETING.
>> SECOND.
>> THANK YOU.
THANKS.
OKAY.
SO THOSE MINUTES--ALL THOSE IN
FAVOR, JUST RAISE YOUR HAND?
ANYONE OPPOSED TO THE APPROVAL
OF THE MINUTES?
THANK YOU VERY MUCH.
I WOULD ALSO LIKE TO CONFIRM THE
FUTURE MEETING DATES AND CALL
YOUR ATTENTION TO THE MEETINGS
LISTED IN THE AGENDA.
YOU CAN SEE THE LIST AND THE
FNLAC MEETING IN JULY IS
CURRENTLY PLANNED AS AN
IN-PERSON MEETING SO IT WILL BE
FUN FOR ALL OF US TO ACTUALLY
GET TO SEE ETCH - OTHER IN
PERSON AS WE'VE BEEN LOOKING AT
OUR LITTLE SQUARES OF PICTURES
FOR TOO MANY MEETINGS.
SO, WE LOOK FORWARD TO THAT.
AND WITH THAT, UNLESS THERE'S
ANY OTHER BUSINESS, WE WILL GO
DIRECTLY TO THE NCI DIRECTOR'S
REPORT AND DR. RATHMELL.
>> GREAT, THANK YOU VERY MUCH.
IT'S NICE TO BE HERE, I'M ALSO
LOOKING FORWARD TO MEETING YOU
ALL IN PERSON.
I WANT TO TART BY THANKING
EVERYONE FOR THE TIME AND EFFORT
AND FOR BEING HERE AND THANK YOU
FOR THE PEOPLE WATCHING ONLINE
AS WELL, I THINK WE'RE REALLY
TRYING TO OPEN UP THE DOORS TO
COMMUNICATION AND SO, THIS IS
HOW WE DO IT BEST.
I'M REALLY THRILLED TO BE IN
THIS ROLE AND HEARING FROM ALL
OF YOU, PARTICULARLY AT THE
FREDERICK NATIONAL LAB.
THIS IS A UNIQUE RESOURCE THAT
DOES INCREDIBLE AND IMPORTANT
WORK IN THE PROGRESS AGAINST
CANCER AND YOUR INPUT IS
INVALENTINED AUTOMOBILE.
SO NEXT SLIDE WILL--SORRYI HOPE
IT'S NOT TOO LONG, THERE'S SOME
MECHANICAL SOUND THAT DECIDED TO
JOIN ME IN MY ROOM.
SO IT IS WHAT IT IS.
SO TODAY'S TALK, I WILL GIVE YOU
A BRIEF INTRODUCTION TO WHO I
AM, HOW I THINK SO YOU CAN START
TO GET TO KNOW ME A LITTLE BIT
AS WELL.
TOPIC OF THE DAY AROUND HERE IS
BUDGET AND WE'LL TALK A LITTLE
BIT ABOUT THE BUDGET OUTLOOK,
JUST SO YOU KNOW WHERE THAT ALL
STANDS AND THEN TALK ABOUT
RESEARCH HIGHLIGHTS AND
HOPEFULLY HAVE TIME FOR SOME
QUESTION AND ANSWER AS WELL.
SO NEXT SLIDE.
OKAY, SO A BIT ABOUT ME, SO I AM
ORIGINALLY FROM THE MIDWEST,
GREW UP IN NEBRASKA AND IOWA, I
WENT ON TO DO MY MD-Ph.D.,
Ph.D. IN BIOPHYSICS AT
STANFORD, I'M A SCIENTIST THAT'S
INTERESTED IN MOLECULAR PATHWAYS
AND CANCER.
I'M ALSO A CLINICIAN, MEDICAL
ONCOLOGIST AND I SEE--MY FOCUS
HAS BEEN ON KIDNEY CANCER
PATIENTS.
I ALSO FOUND A PASSION EARLY IN
MY CAREER AT UNC CHAPEL HILL IN
EDUCATION WORKING WITH THE
MD-Ph.D. PROGRAM AND ASSOCIATE
DIRECTOR FOR EDUCATION AND
TRAINING IN THAT CANCER CENTER.
THAT GOT ME AND PUTTING ALL THAT
TOGETHER, THE 3 LEGS OF THE
ACADEMIC TRIANGLE RESEARCH,
CLINICAL AND EDUCATION ON TO THE
ADMIN TRAITIVE PATH AND LED ME
TO MOVE TO VANDERBILT 8 YEARS
AGO WHERE I WAS HEMEATOLOGY AND
DIVISION ONCOLOGY CHIEF AND THEN
4 YEARS AGO MOVED INTO CHAIRING
THE DEPARTMENT OF MEDICINE JUST
IN TIME FOR THE PANDEMIC SO I
LEARNED LOTS OF GOOD OPERATIONAL
SKILLS ACTUALLY ENOUGH THAT
PROMPTED ME TO GO INTO LEARNING
MORE ABOUT MANAGEMENT AND
ADMINISTRATION AND TO GET A
MASTERS DEGREE IN 2022 IN THE
OWENS SCHOOL OF BUSINESS.
SO WITH THAT, WITH SOME
EXPERIENCES IN MY CAREER THAT
HAVE TAUGHT ME THE VALUE IN
ADVOCACY AND IN LEADERSHIP AND
IN TEAMS, WHICH IS THE
BASKETBALL PLAYER ANALOGY THERE,
I THINK I'M SERVING VERY WELL.
AS I MOVED INTO THE ROLE, THE
STAFF ARE AMAZING AND I'M REALLY
HAVING A GOOD TIME LOOKING AT
THE WHOLE LANDSCAPE OF THE NCI.
SO WHAT DO I VALUE, I REALLY
VALUE LISTENING AND OPENNESS.
THIS IS A GREAT FORUM TO
EXCHANGE INFORMATION AND
THROUGHOUT--I WILL BE WITH YOU
ALL DAY LONG AND WE'LL BE
LISTENING TO THE PRESENTATIONS
AND YOUR COMMENTS AS WELL AS
QUESTIONS THAT YOU ASK, I REALLY
WANT TO KNOW WHAT IS ON PEOPLE'S
MINDS.
I REALLY VALUE TEAM WORK AND
COLLABORATION, THE BASKETBALL
ANALOGY THERE, I LIKE TO USE
BASKETBALL TO YOU KNOW DIVE INTO
ALL OF THE COMPONENTS ABOUT
DEFINITION AND EVERYONE KNOWS
THEIR PART ON THE TEAM, THE
DIVERSITY THAT'S REQUIRED TO
MAKE A GOOD TEAM AND GET IN THE
ZONE AND EXECUTE IN THE FINAL
MINUTES OF THE GAME.
I'M VERY EXCITED TO PUT MY
BRACKET TOGETHER IN A WEEK OR
SO.
AND I REALLY LIKE SOLVING
COMPLEX PROBLEMS, THIS CAN BE
UNTANGLING COMPLICATED MECHANISM
IN A CELL TO WORKING ON A SYSTEM
WIDE OPERATIONAL CHALLENGE.
AND SO, I'M HAVING A GREAT TIME
IN GOVERNMENT REALLY WORKING AT
UNTANGLING THINGS.
SO THAT'S WHO I AM.
LET'S SEE, SO I THOUGHT I WOULD
TELL A LITTLE BIT OF A DIFFERENT
STORY FROM SOME OF THE OTHER
OVERVIEW PRESENTATIONS I'VE
DONE.
LOOKING AT WHERE THE PIVOTAL
EVENTS IN MY CAREER AS A
SCIENTIST OR A CLINICIAN THAT
REALLY COULD TIE WELL TO THE
FREDERICK NATIONAL LAB.
AND I REALIZE THAT A BIG PIVOT
FOR ME WAS THE CANCER GENOME
ATLAS WHICH RELIED HEAVRY ON
RESOURCES OF THE FREDERICK
NATIONAL LAB.
I WAS AT UNC CHAPEL HILL AT THE
TIME WHICH WAS DOING THE
TRANSCRIPT ANALYSIS AND WAS
INVOLVED AS A TISSUE SOURCE SITE
ACROSS THE BOARD BUT WAS VERY
LUCKY TO BE TAPPED TO BE A
LEADER FOR THE 3 DIFFERENT
KIDNEY CANCER PROJECTS.
I WOULD SAY THOSE PROJECTS
REALLY FOR ME HELPED ME SEE
KIDNEY CANCER IN A DIFFERENT
WAY, REALLY TOOK US IN A
DIFFERENT DIRECTION TO WHAT WE
WERE STUDYING IN THE KIDNEY
CANCER ARENA AND WHAT I'VE SHOWN
HERE IS IN OF THE LANDMARK
PAPERS THAT CAME FROM THE CANCER
GENOME ATLAS THAT WE WERE PART
OF OR HAD THE OPPORTUNITY TO
HELP LEAD AND THE TRAINEES OF MY
LAB WHO ALL--THEIR CAREERS WERE
ALSO SHAPED BY THEIR EXPERIENCE
OF BEING MAJOR PARTS OF THE
CANCER DENOAM ATLAS AND
DIFFERENT PROJECTS ON THIS, SO
EACH OF THEM HAD AN OPPORTUNITY
TO COME OF AGE, TO BE
CONTRIBUTING ON A PEER TO PEER
LEVEL ON A REALLY IMPORTANT PART
OF EACH OF THESE PROJECTS.
SO, THIS IS AN EXAMPLE, AND I
HAVE JUST AN EXAMPLE, TO PUSH
THE BUTTON AND MOVE THE SLIDE.
CAN YOU MOVE THE SLIDE,A HEAD OF
WHAT THE TCGA, YOU KNOW YOU ALL
PROBABLY USE THE TCGA OR WERE
INVOLVED IN IT, YOU KNOW THE
REAL VALUE IN SCIENCE, A
NATIONWIDE EFFORT GALVANIZED
AROUND THIS, I THINK THE ABILITY
TO SEE TUMORS FOR THEIR MORE
COMPLETE IDENTITY AS WE GAVE
THEM A WHOLE MOLECULAR CONTEXT,
A LOT MORE COLLABORATIONS, I
KNOW, BUT I KNOW THIS WAS TRUE
FOR EVERYONE STARTED TO WORK
WITH DIFFERENT PEOPLE AND
DIFFERENT KINDS OF PEOPLE,
DISCOVERING NEW AREAS OF WORK,
WE OPENED TONS AND TONS OF DOORS
AND THAT'S JUST ACCELERATES AND
MOVES CANCER RESEARCH FORWARD
AND DEVELOPED A GENERATION OF
SCIENTISTS WHO EXPECT THIS AS
WELL.
SO WITH THAT EXAMPLE, GO AHEAD
TO THE NEXT SLIDE.
I THOUGHT I WOULD JUST KIND OF
SET THAT STAGE THAT THIS IS THE
KIND OF THING THAT WE CAN DO
WITH A FEDERALLY FUNDED RESEARCH
AND DEVELOPMENT CENTER ASK WHERE
IT HAS REALLY SHINED.
I HAVE GREAT EXAMPLES WE WILL
GIVE LATER IN THE TALK, ABOUT TO
LET YOU KNOW, THIS IS--YOU
PROBABLY KNOW MORE THAN ME, THIS
IS A BIG CONTRACT ORGANIZATION,
WE ARE IN THE MIDDLE OF THE
RECOMPETE FOR THIS CONTRACT.
YOU WILL HEAR MORE ABOUT THAT A
LITTLE BIT LATER ON THIS
AFTERNOON WITH THE NEGOTIATIONS
ACTIVELY GOING SO THAT WE CAN
MOVE THIS INTO ITS NEXT PHASE.
ALL RIGHT, NEXT SLIDE.
OKAY, LET'S TALK ABOUT BUDGETS.
SO NEXT SLIDE.
SO THIS IS WHEREY --WHERE WE ARE
TODAY, SO WE HAVE AVERTED SHUT
DOWNS OVER AND OVER AGAIN
INCLUDING LAST FRIDAY AND NOW
HALF OF THE BUDGET HAS BEEN
PASSED BUT WE ARE IN THE SECOND
HALF.
I HAVE A SLIDE ON THAT IN JUST A
SECOND EMPLOY BUT WE'RE LOOKING
AT MARCH 22nd AS OUR NEXT
DEADLINE, THIS WILL BE FULLY
HALFWAY THROUGH OUR FISCAL YEAR,
WITHOUT A BUDGET.
WE'VE BEEN WORKING ON A SET OF
INTERIM GRANT POLICIES THAT WERE
BASED ON THE ASSUMPTION THAT OUR
BUDGET WOULD LIKE BE LIKE LAST
YEAR, WE WILL MAKE FINAL,A
JUSTMENTS AS SOON AS WE KNOW
WHAT OUR APPROPRIATIONS WILL BE.
I WILL SAY I'M VERY EXCITED TO
BE ABLE TO NOT JUST TALK ABOUT
WHAT WE MIGHT DO OR MIGHT NOT
DO, TO WHAT WILL WE BE ABLE TO
DO WHEN WE HAVE A BUDGET TO WORK
WITH.
NEXT SLIDE.
YEAH, THIS JUST GETS A LITTLE
BIT INTO THE WEEDS OF THIS SO
MARCH 8th WAS THE FIRST ISSUE
OF APPROPRIATION BILLS AND THEY
WERE PASSED SO NOW WE'RE LOOKING
AT MARCH 22nd.
WE'RE STILL LUMPED IN WITH
HOMELAND SECURITY, DEFENSE, ET
CETERA.
SO WE WILL BE WATCHING THIS VERY
CLOSELY, AND YOU KNOW REALLY,
WOOING TOGETHER TO MAKE SURE
THAT APPROPRIATORS KNOW HOW
IMPORTANT IT IS TO SUPPORT
CANCER RESEARCH.
I WILL SAY I'VE BEEN DOING ALL
THAT I CAN TO REALLY SUPPORT
THEIR KNOWLEDGE OF WHATIA GOING
ON AT THE NCI.
I'VE BEEN MEETING WITH PEOPLE,
TRYING TO INSURE THAT WE HAVE
GREAT RELATIONSHIPS AND
UNDERSTANDING.
I CAN SAY THAT EVERYONE THAT I
HAVE MET WITH HAS BEEN
SUPPORTIVE AND HOPEFULLY WE WILL
HAVE A BUDGET TO SUPPORT THE
IMPORTANT WORK THAT WE DO HERE.
NEXT SLIDE.
OKAY, SO WHEREVER WE SPEND OUR
MONEY IS IN THIS VARIETY OF
THINGS.
WE HAVE ABOUT 3-QUARTERS OF OUR
FUNDINGS THAT WE THE NCI TO DO
RESEARCH, GRANT CENTERS, ET
CETERA, ABOUT A QUARTER STAYS IN
THE INTRAMURAL PROGRAM,
INCLUDING THE SUPPORT FOR THE
WHOLE GRANTS ADMINITRATION
PROCESS IS IN THAT PART AS WELL
SO, IT'S A LOT OF KNCHT
COMPETING FORCES, ALL OF WHICH
NEED TO BE MANAGED SO THAT WE
HAVE GREAT PORTFOLIO AND THE
FNLAC IS PART OF THAT.
NEXT SLIDE.
SO WHAT WOULD IT COST TO DO THIS
WORK IN SO OUR APPROPRIATION
LAST YEAR WAS 7.3 BILLION
DOLLARS AND AS YOU KNOW THAT
REALLY JUST COVERS THE WORK THAT
WE'RE DOING.
I THINK 1 THING I DIDN'T POINT
OUT ON THAT SLIDE BEFORE WAS
EVERY YEAR, THERE ARE INCREASED
COSTS, NO MATTER WHAT WE DO,
THERE'S ALWAYS INCREASED COST OF
ABOUT A HUNDRED MILLION DOLLARS
IN MANDATORY EXPENSES JUST TO
KEEP FUNDING AT THE CURRENT RATE
OF OUR GRANTS IS AN INCREASED
250 MILLION.
IN THE INTRAMURAL PROGRAM ALONE,
THE INCREASE IN COST OF LIVING
ADJUSTMENT WAS OVER
40 MILLION-DOLLAR.
SO IT'S--IT'SAN EXPENSIVE
BUSINESS AND WE WILL LIKE TO DO
MORE, SO WE HAVE THE OPPORTUNITY
EVERY YEAR TO PROVIDE
PROFESSIONAL JUDGMENT OF WHAT
WOULD IT COST TO DO THE WORK
THAT WE ARE WANTING TO BE ABLE
TO DO, THIS IS NOT EVERYTHING WE
DO BUT OF THE THINGS THAT ARE
EXPECTED OF US.
AND FY24, THAT PROFESSIONAL
JUDGMENT WAS 9.9 BILLION
DOLLARS, THE PRESIDENT
RECOMMENDED 7.8.
WE'RE STILL WAITING TILL
MARCH 22nd OR HOPEFULLY BEFORE
THAT TO KNOW.
BASED ON THE EXPECTATION OF A
9.9 BILLION DOLLAR BUDGET, WE
LOOKED AT WHAT WOULD IT COST TO
TO GROW AT THAT KIND OF RATE AND
THAT WOULD BE LISTEN BILLION
DOLLARS, WE'RE WAITING TO SEE
THE PRESIDENT'S PROPOSAL WILL
COME OUT SOON AND OF COURSE,
FY25 WILL BE WATCHING VERY
CLOSELY.
SO THIS IS WHERE WE ARE.
THANK YOU FOR MOVING THE SLIDE.
WHAT WOULD WE DO IF WE HAD THE
FUNDINGS THAT WE'VE PROPOSED IN
THE PROFESSIONAL JUDGMENT, WE
WOULD REALLY PUSH HARD ON CANCER
CLINICAL TRIALS, REALLY
REVOLUTIONIZING THE WORK WE DO
THERE, GETTING THINGS OUT INTO
THE ENVIRONMENT, ACTUALLY
LOOKING AT ENVIRONMENTAL EFFECTS
ON CANCER RISK.
DOING MORE WITH DATA, MOVERRING
MORE DATA INTO THE CLOUD AND
INTEGRATING DATA SETS TOGETHER
AND UNRAVELING MORE OF THE
INTRICACIES OF CANCER.
SO WITH A FLAT BUDGET, IT'S
REALLY NOT FLAT, THAT'S THE NEXT
SLIDE.
SORRY, GO AHEAD TO THE NEXT
SLIDE.
OH, SORRY, I SKIPPED A SLIDE.
NO, GO AHEAD TO THE 1 WITH THE
GRAPHS.
I FORGOT ABOUT THAT SLIDE.
SO WE'VE BEEN VERY FORTUNATE TO
BE INCREASING OUR BUDGET OR OUR
APPROPRIATION YEAR OVER YEAR AS
YOU CAN SEE ON THE GRAPH ON THE
LEFT AND THE AFFECT THEN IS THE
EXPECT AGZ THAT WE WILL CONTINUE
TO GROW MORE AWARD ANDS CONTINUE
TO GROW THE WHOLE INTRAIZ OF
CANCER RESEARCH FOR THE ENTIRE
UNITED STATES AND THAT HAS BEEN
TRUE, YEAR OVER YEAR, I JUST
WANT TO MAKE SURE THAT THAT'S
VERY CLEAR, THAT'S ALL THERE IN
THE BLUE AND YOU CAN SEE THAT
THAT'S RISEN YEAR OVER YEAR.
WITH EVERY YEAR, THE SIZE OF THE
GRANTS GO UP, SO THE NUMBER OF
DOLLARS THAT GOES INTO EACH
GRANT GETS MORE AND MORE AND SO
TO CONTINUE THIS TRAJECTORY, IT
DOESN'T TAKE AN ECONOMICS DEGREE
TO KNOW THIS WILL COST MORE
COMPARED TO WHAT WE HAD THE YEAR
BEFORE.
NEXT SLIDE.
SO WE'RE EXPECTING OR MODELING
ON A FLAT BUDGET, BUT A FLAT
BUDGET AS A SAID IS NOT TRULY
FLAT.
THERE ARE MANDATORY EXTENSE
PENSS THAT INCREASE, INCREASE TO
COSTS AND RPG POOLS AND WHAT
WILL HAVE TO GIVE, TELLING YOU
THE LEVERS WE HAVE TO PULL, OF
COURSE HOLD THE PAY LINE AND
LOOK AT THAT AS A LEVER WHICH I
HOPE TO BE ABLE TO MAINTAIN,
OTHER PROJECTS IN THE INTRAMURAL
PROGRAM AND IN THE EXTRAMURAL
PROGRAM AS LWE'RE LOOKING AT
BUDGET REDUCKS AND CONTRACT
UTILIZEITION THAT'S DIFFERENT
CONTRACTORS THAT THAN THE
FREDERICK CONTRACT BUT THIS IS
AN AREA THAT WE'RE REALLY
FOCUSING ON BECAUSE CONTRACT
WORK CAN BE MORE EXPENSIVE THAN
TRANSLATIONAL RESEARCH DEGZAL
HIRES: AND WE ARE CURRENTLY
JUST SO YOU KNOW WHERE THINGS
ARE AT THE NCI, WE HAVE PAUSED
HIRING FOR THE MOMENT.
SO THAT WE CAN GET A REAL GOOD
LOOK AT WHAT WE'RE DOING IN
TERMS OF HIRING.
ALL RIGHT, NEXT SLIDE.
OKAY, IF YOU WANT MORE
INFORMATION ABOUT THE BUDGET, WE
TRY TO BE AS TRANSPARENT ABOUT
THE FUNDS WE GET AND WHERE THEY
GO.
THERE ARE SEVERAL GOOD RESOURCES
ONLINE AND INCLUDING GOOD VIDEOS
IF YOU WANT TO TAKE A LOOK, THIS
IS THAT CONTENT.
ALL RIGHT, NEXT SLIDE.
OKAY, SO THAT'S BUDGET.
LET'S TALK ABOUT--A LITTLE BIT
MORE HOW WE'RE MAKING DECISIONS
AND THINKING ABOUT THINGS HERE
AT THE NCI.
SO THE NATIONAL CANCER PLAN WAS
INTRODUCED ALMOST EXACTLY A YEAR
AGO AS A CONCEPTUAL FRAMEWORK TO
THINK ABOUT THE WAY THAT WE
THINK ABOUT CANCER WITH 8 GOALS,
PREVENTING CANCER, DETECTING
CANCERS EARLY, DEVELOPING
TREATMENTS AND DELIVERING
OPTIMAL CARE, MAXIMIZE DATA
UTILITY, ELIMINATE INEQUITS,
OPTIMIZE THE WORKFORCE, AND
ENGAGE EVERY PERSON.
WITH THESE WHOLISTIC GOALS BEING
HOW WE MAKE THE ADVANCED
PROGRESS WE WANT TO MAKE THIS
END CANCER AS WE KNOW IT.
IT TIES CLOSELY TO THE CANCER
MOONSHOT, IT WAS REVIEWED BY THE
PRESIDENT'S CANCER PANEL WHICH
GAVE AN ASSESSMENT FOR EACH GOAL
AND A SERIES OF RECOMMENDATIONS
AS WELL.
NEXT SLIDE.
SO THE CANCER MOONSHOT, HOW DOES
THIS TIE TO THE CANCER MOONSHOT
WITH A ROADMAP LIKE THE NATIONAL
CANCER PLAN, WE KNOW WHAT WE
NEED TO DO TO MOVE FORWARD.
YOU THINK ABOUT THIS LIKE A GAME
PLAN AND A BASKETBALL GAME BUT
THE MOON SHOT IS WHERE WE NEED
TO BE, THE SCORE WE NEED TO
ACHIEVE TO WIN AT THE END, THE
GOAL THAT WE'RE AIMING TOWARD IS
REDUCING U.S. CANCER MORTALITY
BY 50%, BY 20 2047 AND IMPROVIG
THE EXPERIENCE OF PEOPLE AND
THEIR FAMILIES LIVING WITH
CANCER AND SURVIVING CANCER.
SO ENDING CAPSER AS --CANCER ASE
KNOW IT.
TALK ABOUT THE WINS.
IT IS REMARKABLY POWERFUL TO
HAVE ADVOCACY LIKE WE HAVE FROM
THE WHITE HOUSE AND THE BACKING
TO REALLY BE--TRYING TO DO BOLD
THINGS IN A CANCER ARENA, THAT
IS WHERE I'M HERE AND WHY I'M
REALLY EXCITED ABOUT THIS.
SO WE'VE BEEN DOING THESE TALKS
WITH BIG RECENT WINS, THERE ARE
MULTIPLE AND THERE'S ALWAYS A
HUNDRED DIFFERENT THINGS WE
COULD CHOOSE FROM TO TALK ABOUT
HOW AMAZING THE SCIENCE IS, BUT
I THOUGHT WE WOULD PULL
SPECIFICALLY TO LOOK AT WEENKS
THAT HAVE COME FROM THE
FREDERICK NATIONAL LAB.
SO, FIRST, JUST THE RAS PROJECT,
RIGHT?
NOW REALLY COWL MIN 8ING WITH A
FIRST IN CLASS DIRECT INHIBITOR
OF KRAS G12 C, THAT'S BEEN
DEVELOPED WITH THE RAS
INITIATIVE AND IN CLINICAL
TRIALS.
AND CLEARED FDA IN MORE CLINICAL
TRIALS--EXCUSE ME.
WE'RE ALSO SEEING MORE
RANDOMIZED CLINICAL TRIALS ON
HPV VACCINE IN PARTICULAR AND
THIS WAS JUST PUBLISHED, A LARGE
COLLABORATION LOOKING AT SINGLE
DOSING OF HPV WHICH COULD BE A
GAME CHANGER IN TERMS OF GETTING
MORE VACCINE INTO MORE PATIENTS
AND REDUCING THE GLOBAL IMPACT
OF HPV-DRIVEN CANCERS.
WE ALSO HAVE A NUMBER OF BIG
DATA INITIATIVES, REALLY FITTING
WITH THE MAXIMIZING DATA UTILITY
GOAL OF THE NATIONAL CANCER
PLAN, BUT LOOKING AT AI OF FOR
ENDOMEETRIAL CANCER SO THIS IS A
GREAT TIEWPT TO LACK AT AN
UNDERSERVED CANCER THAT HAS
TRADITIONALLY HAD A PRETTY POOR
OUTCOME AND BE ABLE TO CLOSE
GAPS THAT ARE RELATIVE TO
DISPARITIES AS WELL AS MAJOR
SOURCE OF MORTALITY.
YOU WILL HEAR MORE ABOUT THE AI
WORK LATER IN THE PRESENTATIONS
TODAY.
WE ALSO HAVE NEW COLLABORATIONS
ON ANTIBODY AND DRUG CONJUGATES,
REALLY A NEW FRONTIER IN
DEVELOPING BIOPHARMACEUTICAL
ANDS THIS WHERE FREDERICK
NATIONAL LAB CAN REALLY SHINE,
MAKING NEW TREATMENTS WITH FEWER
SIDE EFFECTS THAT CAN TARGET
SOME OF THE MORE RECALCITRANT
CANCERS AND THE FIRST ADC
TARGETING THE C-PROTEIN IS
MOVING INTO CLINICAL TRIALS
WITHIN THE NEXT YEAR OR SO AND
YOU WILL HEAR MORE ABOUT THIS IN
THE NEXT PRESENTATION.
AND THEN I ALSO WANT TO JUST
POINT OUT THAT FREDERICK
NATIONAL LABS IS PARTNERING WITH
THE AMERICAN CANCER SOCIETY AND
CANCER RESEARCH UK TO PUT
TOGETHER THE FIRST U.S. BLACK IN
CANCER MEETING.
THIS IS HAPPENING IN UNI.
I AM REALLY EXCITED THAT THIS IS
KNOW INITIATIVE THAT FREDERICK
NATIONAL LAB IS TAKING ON, THE
BLACK IN CANCER MOVEMENT WAS
TART AS A SOCIAL MEDIA EFFORT
AND HAS REALLY GALVANIZED AND
GOTTEN MORE INVESTIGATORS
ATTRACTED TO CONSIDERING THE
CAREER IN CANCER.
WE NEED A DIVERSE TALENT POOL
AND AN ONGOING DEVELOPED
PIPELINE TO REALLY HAVE THE
INVESTIGATORS AND THE
RESEARCHERS AND ALL THE TALENT
THAT CAN BE BROUGHT TO BEAR FOR
CANCER AND SO EFFORTS LIKE THIS
CAN REALLY MAKE A DIFFERENCE.
ALL RIGHT, NEXT SLIDE.
AND THEN I JUST WANTED TO POINT
OUT, AS YOU KNOW, WE ARE A PART
OF THE CANCER GRANT CHALLENGES,
THIS IS A PARTNERSHIP WITH
CANCER RESEARCH UK, AND AN
OPPORTUNITY TO REALLY THINK BIG,
WHAT ARE INTEREST REALLY BIG
BOLD OPPORTUNITIES TO DIVE IN
AND INVESTIGATORS FROM AROUND
THE WORLD CREATE LARGE TEAMS,
KIND OF COMING BACK TO WHERE THE
POWER IS IN TEAM SCIENCE AND
THERE ARE 5 TEAMS THAT ARE
WORKING ON 4 PROJECTS, THE 4
CHALLENGES ARE, REDUCING CANCER
INIQUITIES, UNDERSTANDING
MECHANISMS OF EARLY ONSET
CANCERS, DEVELOPING DRUGS FOR
SOLID TUMORS IN CHILDREN AND
BROADENING KNOWLEDGE OF HOW
T-CELLS RECOGNIZE CANCER CELLS.
SO ALL TRULY IMPORTANT AWARDS.
EACH TWEAM RECEIVES $25 MILLION
OVER 5 YEARS AND WE'RE REALLY
EXPECTING AND LOOKING FORWARD TO
REALLY MOVING THE NEEDLE.
NEXT SLIDE.
THIS IS MY LAST SLIDE.
JUST CLOSING THOUGHTS.
THIS IS A CHALLENGING YEAR, AND
THERE ARE MORE CHALLENGES TO
COME, WE CERTAINLY UP TO THOSE
CHALLENGES AND YOU KNOW BY BEING
GOOD SCIENTISTS, RIGOROUS,
HONEST AND THOUGHTFUL AND
PRIORITIZING WELL, USING ALL OF
OUR RESOURCES TO THEIR BEST
PURPOSE THAT, IS WHY IT'S SO
VALUABLE TO HAVE A BOARD LIKE
THIS, REALLY WORKING WITH US AND
THINKING ABOUT THE WORK THAT WE
DO SO WE CAN END CANCER AS WEB
CONNECTED KNOW IT, USING THE
NATIONAL CANCER PLAN AS OUR
ROADMAP AND I WILL ADD AND THE
MOON SHOT IS OUR GOAL.
SO I WANT TO JUST THANK YOU.
I SHARED MY THOUGHTS.
I AM COUNTING ON YOU TO PROVIDE
WISE AND CANDID INSIGHTS AND
LOOKING FORWARD TO THE REST OF
THE MEETING.
I AM HAPPY TO TAKE ANY
QUESTIONS.
NTHANK YOU SO MUCH, IT WAS GREAT
TO HEAR FROM YOU.
ARE THERE QUESTIONS FROM THE
COMMITTEE?
>> I ACTUALLY HAD A QUESTION
BUTIME HAVING A HARD TIME COMING
OFF MUTE.
>> HEY,.
>> NICE TO SEE AND
CONGRATULATIONS, I'M REAL LE
EXCITED YOU'RE IN THIS POSITION
AND I'M VERY, VERY EXCITED ABOUT
THE FOCUS ON ENDOMIRROR IMAGE
TRI OLDER PEOPLE CANCER AND
BLACK IN CANCER AND I JUST WAS
WONDERING HOW MUCH IS THAT
INFORMATION BEING DISSEMINATED
AND HOW CAN MORE OF US JOIN IN
THESE EFFORTS WHO MAY NOT BE AS
MUCH AS WARE OF WHERE THE
PROCESS IS AND HOW WE CAN GET
INVOLVED.
>> OH, THAT'S--SO, YOU KNOW,
IT'S ON WEBSITES AND BEING
DISSEMINATED BUT WE CAN DO MORE.
SO IF THE WORD IS NOT OUT, WE'LL
WORK ON PUSHING IT OUT A LITTLE
BIT FURTHER.
I TRIED TO BE MUCH MORE ACTIVE
IN SOCIAL MEDIA, IN PARTICULAR
TALKING ABOUT THIS TODAY, THIS
WILL LIKELY BE PUT THERE, BUT
WE'LL GET THE WORD OUT.
NYEAH, I'M HEADED TO OUR
NATIONAL SOCIETY OF GYNECOLOGIC
MEETING THAT'S HAPPENING WEEK SO
I'M HAPPY TO AMPLIFY AS WELL, SO
THANK YOU NOKAY, WE WILL GET YOU
SOME MATERIALS.
>> LINDA?
>> ACTUALLY, A SIMILAR POINT.
MY DEPARTMENT SUPPORTS
FINANCIALLY AND COMMUNICATIONS
WISE BLACK IN UMPIRESUNOLOGY AND
BLACK IN MICRO, AND IT'S GREAT
THAT BLACK IN CANCER IS GETTING
UNDER WAY BUT THESE ARE REALLY
GREAT DPRASES ROOTS EFFORTS BY
THE PEOPLE IN THE FIELDS BUT I
WONDER IF NIH MIGHT BE ABLE TO
PROVIDE SUPPORT FOR CROSS
GREWSING THEM AND ALLOWING CROSS
DISCIPLINARY WORK AND
INDIVIDUALS WHO WORK AT
INTERSECTIONS TO BENEFIT FROM
MORE THAN 1 OF THESE.
>> YEAH, I LOVE THAT IDEA.
AND I THINK THAT, YOU KNOW FIRST
THAT PROBABLY HAPPENS NATURALLY
BECAUSE THERE ARE CANCER
IMMUNOLOGISTS, ET CETERA BUT
DOING THAT WITH MORE INTENG,
THAT'S A GREAT IDEA.
>> JOHN?
>> CONGRATULESS ULES--CONGRATTUN
YOUR ASHES POINTMENT.
THE SLIDE WHERE YOU SHOWED THE
PLOTS AND THE NUMBER OF GRANTS
GOING UP OVER TIME, CAN YOU
COMMENT, IS THE R-GRANT
MECHANISM GOING UP AS THE SAME
PACE AS THE OVERALL PACE OR
DIFFERENT?
I WOULD ARGUE THAT THAT'S OUR
BROADEST MOST EFFECTIVE
SCIENTIFICALLY DIVERSE POOL OF
ACTIVITIES AND THAT'S WHERE THE
PRIORITY SHOULD BE.
>> YEAH, I AGREE COMPLETELY.
I WENT OVER THAT SLIDE QUICKLY,
THERE WAS A YELLOW BAR ON THAT
SLIDE AND THOSE WERE RO-1S SO
THEY ARE INCREASING AT A SIMILAR
RATE, AND CHAIRMAN AS A
DEPARTMENT THAT REALLY LIVED ON
RO-1s AND SO, HAVE TO MYSELF
AND I GET THAT, THIS IS--THAT'S
OUR BREAD AND BUTTER AND
ABSOLUTELY SUPPORTIVE OF THAT.
>> [INDISCERNIBLE]
>> CONGRATULATIONS ON YOUR
APPOINTMENT.
IN LIGHT OF THE NEW INSTITUTE,
ARP-H, AND AWARDS FOR CANCER CAN
YOU SPEAK TO WHAT IF ANY IMPACT
IT'S BEEN HAVING ON THE NCI
PORTFOLIO AND JUST WITH NCI WARD
ANDS NEW FUNDING OPPORTUNITIES?
>> YEAH, THAT'S A GREAT
QUESTION.
I'M NOT SURE IT'S HAVING AN
IMPACT ON OUR PORTFOLIO, YET, I
THINK THAT WHERE IT'S HAVING ITS
BIGGEST IMPACT IS IN ENCOURAGING
US TO THINK ABOUT WHAT KINDS OF
PROJECTS ARE READY FOR THAT SORT
OF DARP A LIKE ACCELERATION AND
THEY HAVE SEVERAL PROGGENTS THAT
THEY'VE ANNOUNCED THAT ARE
SQUARELY IN THE CANCER SPACE, I
THINK IT'S GREAT, IT IS LARGELY
NCI INVESTIGATORS THAT ARE
LOOKING TO THIS, AND I SUSPECT
THAT AS THESE PROJECTS MATURE,
THEY WILL COME BACK INTO THE
NCI, SO WE'RE LOOKINGA THE THIS
AS A VERY SYMBIOTIC
RELATIONSHIP.
SO I'M REALLY EXCITED TO SEE
WHAT COMES FROM THIS WORK.
>> AND LAST, RODNEY?
>> THANK YOU.
WELCOME EMPLOY [INDISCERNIBLE]
MANY THING VS HAPPENED SO IT'S
GREAT TO SEE THAT.
I WAS TRYING TO FIGURE IT OUT
THIS GRANT CHALLENGE PROJECTS
ALIGNMENT WITH NCI AND FOUND
THEY'RE IN LINE WITH THE
FREDERICK LABS, SO, I THINK ALL
FED RAKE LABS CAN BE
CHARACTERIZATION AND SCALE UP
INTO A CLINICAL TRANSLATION
PROGRAM, SO, DO YOU HAVE ANY
THOUGHTS ON THAT?
I KNOW YOU'RE JUST STARTING,
TAKE THE TEAM SCIENCE AND ALL
THESE, HOW WOULD THAT FIT IN
YOUR PHILOSOPHY AND YOUR
THINKING?
>> YEAH, I'M NOT QUITE SURE I
BEING HEAR ALL THE QUESTION BUT
I THINK YOU WERE ASKING ABOUT
THE CANCER GRANT CHALLENGES AND
HOW THEY INTERSECT WITH THE FED
RICK NATIONAL LAB IN.
>> RIGHT.
>> I DON'T KNOW OFF THE TOP OF
MY HEAD AND I DON'T KNOW IF DINA
OR ANYONE ELSE WANTS TO COMMENT
IF THERE ARE CURRENT CONNECTIONS
BUT THERE CERTAINLY BEING BE, I
WILL IMAGINE IT'S A NATURAL
EXTENSION FOR THE RIGHT KIND OF
PROJECT.
SO I WOULD ACTUALLY HOPE THAT
PEOPLE WOULD SEE IT AS AN
OPPORTUNITY.
>> THANK YOU.
>> CAROL.
NYES, THANK YOU VERY MUCH.
AND CONGRATULATIONS, CAROL BULT
FROM THE NCI LAB, I WAS EXCITED
TO SEE THE AI RESEARCH
APPROACHES TO DIAGNOSIS AND THAT
IS A RAPIDLY, RAPIDLY MOVING
FIELD AND I'M WONDERING IF THERE
ARE PARTNERSHIPS WITH INDUSTRY
PARTNERS IN THAT SPACE WITH
FREDERICK NATIONAL LAB
INVESTIGATORS?
>> I CAN'T ANSWER SPECIFICALLY
THE LAST PART OF THAT QUESTION,
YOU KNOW, WITH ACCURACY BUT MY
SENSE OF EVERY PROJECT THAT I
KNOW IN THE AI SPACE TENDS TO
HAVE A GOOD COLLABORATION--THIS
IS LIKE A RIPE SPACE FOR
PUBLIC-PRIVATE PARTNERSHIPS.
>> YEAH, IT REALLY IS.
>> YEAH, THIS STUFF IS MOVING SO
FAST IN BOTH SPACES REALLY
QUICKLY.
>> OKAY.
THANK YOU VERY MUCH.
>> THANK YOU.
>> AND I THINK WE WILL MOVE ON
WITH ANY OTHER QUESTIONS, WE ARE
RIGHT ON SCHEDULE ANDON TIME.
THIS IS THIS IS A PRESENTATION
BY DR. YOVANDICH, TALKS ABOUT
THE BIOPHARMACEUTICAL
DEVELOPMENT AND PRODECLARATION
AT THE FNLCR.
>> THANK YOU VERY MUCH, I WOULD
LIKE TO THANK DR. RATHMELL AND
DOROSHOW, FOR THE OPPORTUNITY TO
GIVE A PRESENTATION ON DCTD'S
DEVELOPMENT OF
BIOPHARMACEUTICALS AND
PRODUCTION AT THE FED RICK
NATIONAL LAB--FEDDERRIC NATIONAL
LAB AND I THINK YOU SHOULD BE
ABLE TO SEE THE SCREEN NOW, IS
THAT CORRECT?
>> YES, YOU ARE VISIBLE.
>> GREAT.
THANK YOU.
OKAY.
SO HERE ARE THE SET OF TOPICS
THAT I WILL BE GOING OVER IN THE
PRESENTATION, I WILL GIVE A
BRIEF HISTORY AND OVERVIEW OF
DCTK'S APPROACH TO DEVELOPING
BIOPHARMACEUTICALS.
PROVIDE CAPABILITY AND IT IS
HIGHLIGHT RECENT ACCOMPLISHMENTS
OF THE BIOPHARMACEUTICAL
DEVELOPMENT PROGRAM HERE AT THE
FREDERICK NATIONAL LAB.
AND DESCRIBE OR HIGHLIGHT SOME
OF THE RECENT SUPPORT THAT THE
BDP IS PROVIDING FOR THE CELL
THERAPY FIELD AND MORE RECENTLY
THE CANCER ADAPTIVE CELL THERAPY
INITIATIVE THAT'S BEEN SET UP
AND THEN I WILL WIND UP THE
PRESENTATION WITH AN OVERVIEW OF
ACCESS, HOW FOLKS CAN ACCESS THE
BDP AS WELL AS RECENT
COLLABORATION OPPORTUNITIES THAT
HAVE COME UP.
SO WHY DOES DCTD SUPPORT
BIOPHARMACEUTICAL DEVELOPMENT?
WE WANT TO ROUGH ATOM VIED
RESOURCES THROUGH THE COMMUNITY,
FILL GAPS AND FOSTER DEVELOPMENT
OF NEW BIOTECHNOLOGIES AND WE
WANT TO DISSEMINATE THE
KNOWLEDGE WE'VE AGAINED AND
SHARE THAT WITH ANY UNIQUE
RESOURCES WE HAVE WITH NIH
PARTNERS.
SO A BRIEF HISTORY AND OVERVIEW
OF OUR APPROACH TO
BIOPHARMACEUTICAL DEVELOPMENT,
WE'VE ACTUALLY BEEN ARK ROUND
SINCE THE 70S, THE ORIGINAL
PROGRAM WAS THE BIOLOGICAL
RESPONSE MODIFIERS PROGRAM AND
IT WAS THEN IN THE DIVISION OF
CANCER THERAPY, THE BRMP
SUPPORTED A LOT OF THE EARLY
CLINICAL STUDIES WITH INTERFORON
AND IRPT LUKEIN 2, THIS WAS
MOSTLY DONE THRAW CONTRACTS AND
GRANT ANDS CLINICAL TRIAL
SUPPORT THAT ARE PROVIDED TO THE
CLINICAL CENTER AS WELL AS A
SATELLITE CLINICAL SITE HERE IN
FREDERICK AT THE TIME.
THE PROGRAM SUPPORTED A LOT OF
ACQUISITION OF MONOCLONAL
ANTIBODIES, MOVED IN SOME OF THE
EARLY VERSIONS OF TUMOR VACCINE
STRATEGIES, ONCO LYTIC VIRUS AND
BACTERIA AND NOW IN CELL AND
GENE THERAPIES.
SO BIOLOGICS AS MOST FOLKS KNOW
HAS EVOLVED QUIT SIGNIFICANT LYE
THE LAST 10-20 YEARS STARTING
WITH CRUDE ISOLATES AND
EXTRACTS, WORKING INTO RECOMBIN
ANT PROTEIN AND PURIFICATION
PRODUCTION, THEN WITH THE ADVENT
OF CLINICALLY ACTIVE AND
SUCCESSFUL ANTIBODY THERAPIES.
AS DR. RATHMELL MENINGED WE ARE
NOW MOVING INTO THE CONJUGATE
AGENTS AND ANTIBODIES, AND
THERE'S BEEN A NUMBER OF
SUCCESSFUL VIRUS PRODUCTS AND
VIRUS-LIKE PARTICLE ANDS A LOT
OF THE FIELD AND MOVING INTO
BACTERIAL BASED THERAPIES AS
WELL AND MORE RECENTLY, WITH THE
SUCCESS OF TILL THERAPIES AND
AUTOLOGOUS THERAPIES WE ARE NOW
MOVING INTO A TERRITORY OF
ENGINEERED CELLS AND BIOLOGY.
SO WHAT ARE THE TYPICAL
MILESTONES, HOW DO WE DEVELOP
AND APPROACH THE TRANSLATION OF
BIOLOGICS.
FIRST IS IT WHAT YOU THINK IT
IS?
WE DO A LOT OF PRECLINICAL
TESTING OF THE MATERIAL TO
ANALYZE THE STARTING MATERIALS
FOR YEEN SUITABILITY, WE APPLY
WHAT WE CALL SSISQF, THAT STAND
FORS DETERMINING SAFETY, IESHES
DENTITY, STRENGTH OR POTENT
STATE ENSEL OF THE AGENT,
QUALITY OF THE MATERIAL AS WELL
AS THE PURITY OF THE MATERIAL.
NEXT QUESTION IS CAN WE MAKE
ENOUGH IN THIS IS WHERE THE
PROCESS DEVELOPMENT STAGE COMES
IN FOR SCALE ASK FEASIBILITY,
ASSAY DEVELOPMENT AS WELL AS
STANDARD OPERATING PROCEDURES
AND FORMULATION STABILITY.
THE NEXT STEP IS TO GENERATE
ENOUGH REFERENCE MATERIAL AND
THIS DOESN'T ONLY APPLY TO THE
BIOLOGIC CANDIDATE BUT ALSO TO
THE STARTING MATERIALS, THE
PRODUCTION MATERIALS, THE CELL
BANKS AND THE VIRUS BANKS.
OTHER THAN THE SET TESTING
SPECIFICATIONS, THIS IS WHERE
THE QC GROUP STEPS IN FOR
DEVELOPING ANALYTICAL QUAL
IIVESS FOR PRODUCT RELEASE, WE
ALSO DO SOME FORCED DEGRADATION
STUDIES TO INFORM THE UPCOMING
STABILITY PROGRAM, AND THEN THE
NEXT BIG QUESTION IS, CAN WE
MAKE THE CLINICAL LOT?
THIS WHERE THE DRESS REHEARSAL
COMES THROUGH, WE DO A PILOT
MANUFACTURING OR ENGINEERING
LINE AS ITS SOMETIMES CALLED TO
PRODUCE MATERIAL THAT CAN BE
USED FOR REFERENCE STANDARDS AS
WELL AS FOR THE DIRECT IND
TOXICOLOGY AND FUTURE ED
CREDIBILITY STUDIES.
THE NEXT STEP IS TO LOOK AT
PRECLINICAL SAFETY STUDIES THIS
WILL BE PART OF SUPPORT FOR AN
I& D FINDINGINGS, RANGE STUDIES
AND TOXICOLOGY AND DISTRIBUTION,
THE LAST BIG STEP IS THE
MANUFACTURING.
THIS INVOLVES QC AND QA RELEASE,
ALTHOUGH THE REGULATORY
DOCUMENTATION ASSOCIATE WIDE THE
BIOLOGIC [INDISCERNIBLE].
AND THEN LAST BUT NOT LEAST THIS
IS REALTIME SUSTAINABLE, THIS IS
A SUBSET OF TESTS THAT ARE USED
AND DESIGNED TO DETECT
DEGRADATION AND CONTAMINATION
AND THEN SOMETIME AMONG THESE
LAST FEW POINTS WE HIGHLIGHT AND
RECOMMEND THAT EVERYBODY REACH
OUT TO THE FDA FOR PREI& D
MEETING TO MAKE SURE THEY'RE ON
THE RIGHT PATH FOR SUCCESSFUL I
D.
>> SO WHAT WE DO, AS THE
PROJECTS COME IN AS WE SET UP A
SET OF GENERIC QUESTIONNAIRES,
OR GENERATED IRBIC GENERAL
QUESTIONS FOR BIOLOGICS TO GAUGE
THE DEVELOPMENTAL READINESS OF
THE AGENT.
IT ADDRESSES THAT SISQP, I
MENTIONED EARLIER AND CONTAINS
SPECIFIC QUESTIONS FOR A VERY
SPECIFIC BIOLOGICS THAT PERTAINS
TO BECOMING A PROTEIN, VIRUSES,
PEPTIDES AND CELL PRODUCTS.
ALL RIGHT, SO TO GO OVER THE
CAPABILITIES AND RECENT
ACCOMPLISHMENTS OF THE
PHARMACEUTICAL DEVELOPMENT
PROGRAM, WE SET UP THE BDP IN
THE EARLY NIEND 90S IN
FREDERICK, TO PROVIDE TECHNICAL
EXPERTISE THAT'S NOT READILY
AVAILABLE IN THE COMMERCIAL
MARKET AND THIS FITS NICELY WITH
THE MISSION OF--THE BDP CONDUCKS
FEASIBILITY STUDIES ON PROJECT
CANDIDATES.
THEY DEVELOP MANUFACTURING
PROCESSES AND ASSAYS PERFORM
THE GMP MANUFACTURING INCLUDING
FILL AND FINISH AND PRODUCT
RELEASE.
THEY ALSO PRODUCE AND SUBMIT ALL
THE DOCUMENTATION REQUIRED FOR
FDA AND REGULATORY FILINGS AND
THEY'VE SET UP A VERY NICELY
STREAMLINED PROCESS, FOR TECH
TRANSFER, OF EVERYTHING THAT
THEY'VE WORKED ON AS
COMMERCIALENTITY IS COME INTO
PLAY AND TAKE OVER THE PRODUCT
FOR FURTHER DEVELOPMENT.
THEY ALSO HAVE A VERY SOLID GENE
TRAINING PROGRAM FOR THEIR STAFF
AS WELL AS EXTERNAL PARTNERS,
TOO, SINCE THE LATE 90S THEY
PRODUCED MORE THAN 260
INVESTIGATIONAL AGENTINGS.
AS YOU SEE FROM THE PIE CHART
THERE, AS A BREAK DOWN OF THE
NATURE OF THE BIOLOGICS, THE
RECOMBIN ANT PROTEINS OR
PEPTIDES FOLLOWED CLOSELY AND
INCREASINGLY BY CELLULAR
PRODUCTS THAT WILL GET TO YOU
LATER IN THE PRESENTATION ALONG
WITH MONOCLONAL ANTIBODIES,
VIRAL VECTORS AND VIRUS LIKE
PARTICLES.
SO THE BDP, HERE IS--HERE AT THE
ADVANCED TECHNOLOGY RESEARCH
FACILITY IN FREDERICK, IT IS IN
2 WINGS OF THE FACILITY HERE AND
MULTIPRODUCT PILOT FACILITY FOR
MAKING BIOPHARMACEUTICALS AND
CELLULAR PRODUCTS AND THE OVER
ALL SIZE IS ABOUT 66,000 SQUARE
FEET AND A THIRD OF WHICH IS THE
GMP MANUFACTURING AREA.
THAT AREA CONTAINS SEPARATE SETS
OF ROOMS OR TRAINS FOR
PRODUCTION FROM EUKARYOTIC CELLS
OR PROPROKARYOTIC CELLS LIKE
E.COLI PRODUCTION AND PURE IIVES
AND THEN A SEPARATE SET OF
FILL/FINISH VIAL BLAIBLING AND
INSPECTION, UP TO 10,000 USING
OUR AUTOMATED FILLER AND THEN UP
TO 2500 FOR MANUEL FILLED.
THE FACILITY HAS A
SELF-CONTAINED VIRUS
MANUFACTURING SUITE RUN ON ITS
OWN AIR HANDLER ANDS RUNNING
WITH SEPARATE ENTERS AND
CHANGING ROOMS AND THEN RECENTLY
WE RENOVATED SOME R&D SPACES, AS
WELL AS OFFICE SPACE TO PROVIDE
4 NEW GMP CELL THERAPY SUITES
AND THEN THE REST OF THE
FACILITY IS MADE UP OF LABS FOR
THE QC GROUP FOR PROCESS
DEVELOPMENT AND FOR WAREHOUSING
PRODUCT ANDS RAW MATERIALS.
SO THIS IS JUST A SAMPLING OF
SOME OF THE STATE-OF-THE-ART
EQUIPMENT THAT THE BDP HAS
STARTING GOING FROM LEFT TO
RIGHT HERE.
WE'VE SWITCHED OVER TO
DISPOSABLE BIOREAGHTORS HERE UP
TO 200 LITERS THAT WE CAN GROW,
SHOW CELLS OR 293 CELLS THAT ARE
PRODUCING RECOMBIN ANT PROTEINS
AND ANTIBODIES, AND THEN DOWN
BELOW THERE, THERE'S THE
FERMENTERS FOR THE E.COLI AND
[INDISCERNIBLE] FERMENTATION,
SCALES WITH BE PRODUCED THERE
ANDOR WORKFORCE FOR PURIFICATION
IS THE ACTIVE SKID SEEN IN THE
TOP ALONG WITH A PACKED COLUMN
USED IN THE PURIFICATION
PROCESS.
DOWN AT THE BOTTOM WE HAVE 1 OF
MANY NEXT QUANT MULTICELL
SORTERS THAT ARE USED TO
QUANTIFY AND SORT CELL PROTEINS
AND THEN OUR WORK HOUSE FOR CELL
THERAPY PRODUCTION AND A NICE
CLOSED SYSTEM FOR ISOLATING,
TRANSDUCING AND EXPANDING CELL
PROD UBIQUITINNATIONS.
UP THERE IN THE UPPER RIGHT HAND
CORNER AND JUST 1 EXAMPLE OF
MANY PIECES OF QC EQUIPMENT THAT
WE UTILIZE, THIS IS AN ADJUVANT
HPLC, FOR DETERMINING THE SISQP,
OF THE BIOLOGICAL PRODUCTS AND
THEN DOWN AT THE BOTTOM IS A
BRAND NEW SEMIAUTOFILLING
MACHINE THAT REPLACES OUR OLD
FLEXICON THAT HAS JUST BEEN
INSTALLED OVER THE LAST FEW
MONTHS AND HANDLES THOSE
AUTOMATED FILLS, UP TO 10 MILL
VIALS.
SO, THE BDP FOLLOWS WILL CODE
CODE OF FEDERAL RELATIONS, 21
CFR211, THIS PERTAINS--DOING ALL
THE GMP PRODUCTION AND THE
PRODUCT CONTROLS ASSOCIATE WIDE
THAT AND THE FINISH ASPECTS, THE
GENERATION AND MAINTENANCE AND
REPORTS ARE ALSO INCLUDED YOU
SHOULD THAT CODE OF FEDERAL
REGULATIONS AND BECAUSE THEY
FOCUS ON EARLY STAGE
DEVELOPMENT, SO FOR PHASE 1,
MAYBE PHASE 2, OR CERTAIN LYE
NONPIVOTAL CLINICAL TRIALS, THEY
HAVE ESTABLISHED A QUALITY
MANUEL THAT DRIEBS HOW THEY WILL
ADHERE TO 21 CFR211 BUT WITH AT
THE LEVEL THAT IS PHASE
APPROPRIATE AND THE FDA ACCEPTS
THIS FOR EARLY PHASE DEVELOPMENT
OF PRODUCTS.
DIGGING INTO A BIT MORE DETAIL
ON THIS, ON THE QUALITY SYSTEMS
WITH REGARDS TO ORGANIZATION AND
PERSONNEL, THE BDP PERSONNEL ARE
VERY HIGHLY TRAINED AND GO
THROUGH GMP TRAINING EVERY YEAR.
EACH PERSON HAS THEIR OWN
TRAINING CURRICULUM BASED ON
WHICH DEPARTMENT THEY'RE IN AND
JOB FUNCTION AND SPBTS QA AND QC
PROVIDE REGULATORY AND OVERSIGHT
AND VENTERS AND ALSO INTERNAL
AUDITING OF THE INTERNAL
DEVELOPMENT PROGRAMS AND THE
DEVELOPMENT GROUP AND THE
MANUFACTURING LABS HERE.
AS REQUIRED BY 21 CFR211 THE QA
GROUP HAS AN INDEPENDENT
REPORTING STRUCTURE THAN THE
REST OF THE MANUFACTURING AND
DEVELOPMENT GROUP AT BDP.
WITH REGARDS TO DOCUMMATION
THERE'S STANDARD OPERATING
PROCEDURES FOR EVERY ASPECT OF
THE PROGRAM INCLUDING
MANUFACTURING, QC TESTING,
FACILITY OPERATIONS, EQUIM
OPERATIONS, AND ENVIRONMENTAL
MONITORING THERE ARE MASTER
PRODUCTIONS RECORDS FOR EACH
PRODUCT AND THEN DURING THE
MANUFACTURING RUN A BATCH
PRODUCTION RECORD IS COMPLETED
UNTIL THAT FOR APPROPRIATE DOCK
ULTIMATELIATION, QC TEST REPORTS
ARE GENERATED ACCORDING TO 21
CFR 211 AND THE PRODUCTS ALL
INCLUDE MASTER SPECIFICATIONS
AND CERTIFICATES OF ANALYSIS
ASSOCIATED WITH THEM.
THE UTILIZED MASTER CONTROL AS
OUR VALIDATED ELECTRONIC
DOCUMENT MANAGEMENT SYSTEM THAT
HOLDS ALL OF THE SOPs,
TRAINING RECORDS AND MASTER
PRODUCTION RECORDS.
WITH REGARDS TO FACILITIES AND
EQUIPMENT, THE FACILITY BEFORE
CONSTRUCTION WAS INITIATED IN
2011 WENT THROUGH AN FDA REVIEW
AND A TYPE-C MEETING SO WE GO
BUY-IN ON THE FDAOT DESIGN
FACILITY, ALL THE UTILITIES AND
STERILIZATION ARE UNDERGO RECERT
IVENGZ EACH YEAR.
QUANTITATIVE INSTRUMENTATION,
ALSO ARE ON ANY CALIBRATION
PROGRAM, REGULAR CALIBRATION
PROGRAM AND THEN PRODUCT CONTACT
EQUIPMENT AND VALIDATED, REALLY
DON'T HAVE THE RESOURCES TO DO
COMPLETE VALIDATION ON EVERY
SINGLE PIECE OF EQUIPMENT, SO WE
UTILIZE A RISK BASED APPROACH,
BASED ON PRODUCT SAFETY AND
QUALITY IMPACT ASSESSMENT.
THE AUTOMATED PHONE EQUIPMENT IS
REVALIDATED WITHIN 6 MONTHS OF A
PRODUCT FILL.
WITH REGARDS TO MANUFACTURING,
RAW MATERIALS ARE ASSIGNED PART
NUMBERS,A CORDING TO
REGULATIONS, THEY EACH HAVE
THEIR OWN SET OF PRODUCT CONTENT
AND THEN WHAT'S INTERESTING IS
THAT RECEIVING NUMBERS ARE
ASSIGNED TO EACH PACKAGE THAT'S
RECEIVED.
O IF WE ORDER A RAW--SO IF WE
ORDER A RAW MATERIAL OF THE SAME
VENDOR OF THE SAME MANUFACTURING
LOT BUT IT'S RECEIVED ON 2
SEPARATE DAYS, EACH 1 OF THOSE
ARE--EACH 1 OF THOSE SHIPMENTS
RECEIVE A SEPARATE NUMBER FOR
APPROPRIATE TRACKING IS REQUIRED
BY THE REGULATION.
ALL OF OUR FACILITIES AND AREA
CLEARANCES ARE PERFORMED BY QA
AND BATCH PRODUCTION RECORDS AS
I MENTIONED EARLIER, DOCUMENT A
PRODUCTION PROCESS, THE FULL
FINISH AND CRITICAL GENE
MANUFACTURING STEPS INCLUDE AN
IN-PERSON QA OBSERVATION TO
MONITOR AND ASSURE THAT STEPS
ARE BEING CONDUCTED AS
INSTRUCTED.
QA REVIEWS THESE COMPLETED BATCH
PRODUCTIONS RECORDS AND RELEASES
PRODUCTS FOR CLINICAL USE AND
THE REGULATORY GROUP GENERATES
THE CHEMISTRY MATERIALS AND
CONTROL, DOCUMENT FOR REGULATORY
FILING.
SO NOW MIEWFING INTO WHAT I
WOULD LIKE TO HIGHLIGHT SOME OF
THE RECENT CAPABILITIES, THAT
THE BDP HAS ESTABLISHED AND SOME
FOLKS IN THIS COMMITTEE HAVE
HEARD SOME PRESENTATIONS ON
THIS, BUT ABOUT 5 OR 6 YEARS AGO
OR SO, WE ASK BDP TO SET UP A
CAPABILITY TO DEVELOP AND
MANUFACTURE AHATOLOGIOUS KARKS-T
CELL PROD UBIQUITINNATIONS AND
THEY DID THAT SUCCESSFULLY AND
FOR THE LAST FEW YEARS WE'VE
BEEN SUPPORTING CLINICAL TRIALS
WITH THE NUMBER OF NEW CLINICAL
TRIALS COMING ONLINE PRETTY SOON
THAT WILL BE SUPPORTING.
SO WHAT THIS CAPABILITY
ENCOMPASSES IS 5 GMP SUITES, 2
ARE FLEXIBLE FOR VIRUS
MANUFACTURING, INCORPORATE
CLOSED MANUFACTURING SYSTEMS
LIKE THE PRODIGY EQUIPMENT I
SHOWED EARLIER, PROCESS
VALIDATIONS ARE ESTABLISHED TO,A
SURE QUALITY HIGH QUALITY AND
STERILITY OF THE PRODUCT.
PROCESS QUALIFICATION IS
ESTABLISHED AS WELL, AND WHAT
THIS DOES IS ALLOWED FOR A VERY
RAPID PRODUCT RELEASE AS YOU CAN
SEE FROM THE DIAGRAM THERE WITH
TEABED WITHIN 10 WEEKS OR SO THE
BDP AND FOR THE STARTING
MATERIAL.
THE BDP IS ALSO ESTABLISHED
SHIPPING AND PRODUCT WAS
LOGISTICS THAT ARE CAPABLE OF
SUPPORTING MULTICENTERRED TRIALS
WITH THE BDP BEING THE CENTRAL
MANUFACTURING SITE AND WHAT THIS
ENDS UP BEING OR PRODUCING IS A
REALLY GOOD QUALITY
MANUFACTURING PROCESS TO ADD
RIGOR AND REPRODUCIBILITY TO THE
CLINICAL RESEARCH PROGRAM
THEY'RE SUPPORTING.
AND BY SUPPORTING MULTISITE
CLINICAL TRIALS, IT REALLY
BENEFIT, IT REALLY HAS A
POSITIVE IMPACT ON RURAL RATES
OF THESE TRIALS.
SO ASSOCIATED WITH THE CELL
THERAPY PLATFORM ESTABLISHMENT,
THE BDP HAS ALSO ESTABLISHED
PLATFORMS FOR PRODUCING GMP
GRADE LENTIVIRUS AND GAMMA VIRUS
THAT ARE USED FOR ENGINEERING
THE CELL PROD YOUS.
LENTIVIRUS PLATFORM CONSISTS OF
HEK293 CELL BRAINK AND IT'S A
TRANSVEKS PROCESS ALONG WITH THE
YEEN OF PLASMA THAT'S EXPRESSING
THE CAR CONSTRUCT, THE
LENTIVIRUS PLATFORM INCLUDES A
CHROMATOGRAPHY AND AFFAIRS TEAM
LEADERRER FILTRATION STEP TO
INCREASE CONCENTRATION AND
PURITY OF THE VECTOR.
THIS IS A SUSPENSION BASED
CULTURE THAT IS CURRENTLY AT THE
10 LITER SCALE WHICH, YOU KNOW
SATISFIES OUR SAFETY HERE AT THE
FREDERICK NATIONAL LAB AS WELL
AS MEETS THE CLINICAL NEED FOR
MANUFACTURING FOR--AT LEAST 1
PHASE 1 TRIAL, IF NOT 2.
BUT BECAUSE THE CELLS ARE IN
SUSPENSION PLATFORM, THIS IS A
SCALABLE PROCESS, SO IF MORE
MATERIAL IS NEEDED OR IT NEEDS
TO BE TECH TRANSFERRED TO
COMMERCIAL ENTITY, THAT CAN
EASILY SCALE UP PRODUCTION, NOW
AGAIN A RETROVIRUS, PRODUCTION
PLATFORM, RETROVIRUSES ARE MORE
LABEL THAN LENTIVIRUSES SO THEY
CAN'T STAND THE CHROMATOGRAPHY
TEPS SO THIS PURIFICATION
PROCESS, IT'S A TRANSIENT
TRANSFECTION BASED PROCESS, 10
LITER SCALE, SUSPENSION CELL
LINE THAT, YOU KNOW THAT IS AS
PRODUCED BY JUST CLARIFYING
SUPER 98ENT AND THEN
CONCENTRATING THE YIELD OF THE
LENDY VIRUSES RANGES FROM
10-SEVENTH, TO 1 TIMES TO THE
NINTH IN THE LINE, AND THE
RETROVIRUS PRODUCTIVITY IS
SOMEWHERE BETWEEN 5 TIMES TO THE
SIXTH AND 5 TIMES TO THE SEVENTH
TRANSDUCTION UNITS PERMILL
BASED ON THE INDICATOR LINE.
SO ANOTHER RECENT TECHNOLOGY AND
CAPABILITY BDP HAS STOOD UP IS
CRSPR CELL BASED ENGINEERING.
THEY'VE BEEN ABE TO SOURCE ALL
THE STARTING MATERIALS FROM GMP
COMPLIANT SOURCES INCLUDING THE
GUIDE RNAs, THAT THE CAS 9
PROTEIN AND THE DNA TEMPLATE
THAT'S USED FOR INTRODUCING IN
THIS CASE, PARSIGNIFYQUENCE OR
ANYTHING ELSE THAT NEEDS TO BE
INTRODUCED INTO THE CELLS.
SO IT'S AN ELECTROPRORATION
BASED PROCESSION AND THE BDP HAS
BEEN ABLE TO DEMON TRAIT
EFFICIENT, ENDOGENOUS PC R KNOCK
OUT GREATER THAN 98% AT BOTH OF
THOSE SITES AND EFFICIENCY OF
WHAT UP TO 40% WHICH IS GOOD
CONSIDERING THE RECENT REPORTS
IN THE FIELD OF THE AVERAGE
AROUND 15-TBEPT% WITH TWEAKS TO
THE BDP'S GODDEN UP TO 40%
KNOCK-IN EFFICIENCY.
I WANT TO HIGHLIGHT A FEW OF THE
SUCCESSFUL COMMERCIALIZATION AND
PRODUCT LICENSURES THAT HAVE
COME OUT OF THE BDP, SO WE'VE
GOT [INDISCERNIBLE] WHICH HAS
BEEN PULLED FROM THE MARKET BUT
THIS WAS THE FIRST PRODUCT THAT
THE BDP SAW GO-2
COMMERCIALIZEITIONS ANTICD TOXIN
FOR HAIRY CELL LEUKEMIA,UNE
TUXIN FOR PEDIATRIC
NEUROBLASTOMA, LERAPOLTUREV, IS
IN THE LATE STAGES OF
COMMERCIALIZATION AND THAT IS
RECOMBIN ANT POLIO VIRUS
PROVIDED BY THE PROGRAMS HERE
THAT IS DEVELOPED BY ISTARI, FOR
GLUE MARIOUS O BLASTOMA,
MELANOMA, NONMUSCLE INVASIVE
BLADDER CANCER AND THEN ANOTHER
PRODUCT INITIALLY DEVELOPED HERE
IS ANSELAMIMAB, IT TARGETS THE
GAMMA LIKE CHAIN THAT'S IN
AMYLOID PLAQUES FOR PRIMARY
AMYLOIDOSEIS AND THAT'S BY
ALEXION.
SO NOW I WANT TO HIGHLIGHT AND
GO INTO MORE DETAIL ON THE
SUPPORT EXPOSURE TO RADIATIONS
THAT THE BDP IS PROVIDING FOR
THE CELL THERAPY COMMUNITY AND
FOR THE CANCER CELL THERAPY
ADOPTIVE NETWORK.
SO WHEN THEY TOAD UP THEIR
MANUFACTURING PLATFORM AND
CAPABILITY, 1 OF THE FIRST TASKS
WAS TO SUPPORT A MULTISITE
CLINICAL TRIAL FOR RELAPSE OR
FACTORY AML, YOUNG ADULT ANDS IN
CHILDREN.
THIS IS A I& D SPONSORED BY THE
NATIONAL MARROW DONOR PROGRAM
AND THE PRIMARY STUDY PI IS AT
THE CENTER FOR CANCER RESEARCH.
AND SO TO DATE, THE BDP HAS
PRODUCED 26 PRODUCTS,
SUCCESSFULLY, AND HAVE SUPPORTED
THE CLINICAL TRIAL UP TO THE
MAXIMUM TOLERATED DOSE AS YOU
SEE THERE, 10 TO THE SEVENTH
CELL KILOGRAM, UNFORTUNATELY,
ALTHOUGH THE MANUFACTURING WAS
VERY SUCCESSFUL LEER AT THE BDP,
THIS ARM OF THE STUDY DID WAS
HALTED FOR FUTILITY BUT THE
CLINICAL PROGRAM KD--SALLY XA
HAS BEEN ABLE TO FILE AN I& D
AMENDMENT TO ADD AN ALOE
GENERATED AIC ARM TO THE STUDY
WHICH WILL USE CELLS FROM
HEALTHY HLA MATCHED DONORS FROM
AML PATIENT ANDS THE BDP WILL
MANUFACTURE FOR THAT ARM
SHORTLY.
ANOTHER MULTISITE TRIAL THAT IS
ONGOING AND SPONSORED BY DCTD,
THROUGH INITIALLY THE PICN, AND
NOW IT'S TRANSITIONED OVER TO
THE PET CTN NETWORK, SO THIS BPI
IS ROSIE CAP LANAT CCR AND THIS
IS A GD2 TARGETED CAR-T FOR
OSTEOSARCOMA OR NEUROBLASTOMA.
THE BDP HAS MANUFACTURED PRODUCT
FOR THE FIRST DOSE LEVEL, IT WAS
DETERMINED THAT THIS WAS THE
BTD, AND THE NEXT STEP WAS TO GO
DOWN AND ONCE THE TRANSFER HAS
BEEN SUCCESSFULLY MOVED TO PEP
CTN THEN THEY WILL RESUME
MANUFACTURING FOR THIS MULTISITE
TRIAL.
OKAY AND NOW KIND OF OUR LATEST
AND MUCH MORE VERY CHALLENGING
STEP IN CELL THERAPY WORLD AND
SUPPORT FOR THE RECENTLY FUNDED
CANCER ADOPTIVE CELL THERAPY
NETWORK OR CAN ACT.
THIS NETWORK HAS BEEN SET UP TO
FOSTER INNOVATION AND PROMOTE
EARLY STAGE CLINICAL TESTING OF
NOVEL IMMUNO CELL BASED THERAPY
FOR SOLID TUMORS IN ADULTS AND
PEDIATRIC PATIENT ANDS IT REALLY
LEVERAGES OUR RESOURCES HERE AT
THE FREDERICK NATIONAL LAB
INCLUDING THE BIOPHARMACEUTICAL
DEVELOPMENT PROGRAM TO SUPPORT
THESE IMRANTS.
SO YOU KNOW THE GOALS STATED
THERE DEVELOP AND ENHANCE
CELLULAR PRODUCTS, EITHER
GENETICALLY MODIFIED OR THRAW
OTHER MANIPULATIONS FOR
TREATMENT OF ADULLS AND
PEDIATRIC SOLID TUMORS, SUPPORT
EARLY PHASE CLENICAL TRIALS,
EXPLORE IMAGING AND BIOMARKER
DEVELOPMENT, EXPAND OUR
UNDERSTANDING OF THE MECHANISMS
OF ACTION AS WELL AS RESISTANCE
MECHANISMS THAT SPRING UP AND
EVALUATE STRATEGIES TO MODULATE
THE IMMUNOSUPPRESSIVE TUMOR
MICROENVIRONMENT.
SO I KIND OF AMPLIFIED THE
BUBBLE FOR THE IC N CORE BECAUSE
IT PERTAINS TO THE SUPPORT THAT
THE BDP IS PROVIDING TO THIS
NETWORK BUT JUST TO GIVE YOU AN
UPDATE, THIS NETWORK IS IN THE
PRACTICES ASSESSES OF BEING
ESTABLISHED SO RIGHT NOW WE HAVE
FUNDED THE 4 DARK BLUE BUBBLES,
THE 4 ADULT UG3 GRANTS AND THE
U24 COORDINATING CENTER.
WE ARE IN THE PROCESS OF
REVIEWING, GRANT REVIEWING FOR
THE PEDIATRIC INDICATIONS AND
HOPE TO GET AT LEAST 1 IF NOT 2
OF THOSE GRANTS FUNDED IN THE
NEXT 6 TO 8 MONTHS AND A SERIES
OF OF SUPLEMS ARE ANTICIPATED TO
BRING IN P30, P50 CANCER
TRUSTEES AFFILIATES INTO THE
NETWORK.
SO RIGHT NOW OF THE 4 GRANTS, 3
OF THOSE ARE USING THE LAB,
IMMUNE CELL CORE, THE BDP IS
PART OF THAT CORE, OR THE ICN
CORE.
THE CRITERIA ARE IF GETTING BDP
SUPPORT OR ICN SUPPORT IS THAT
THE APPLICANTS HAPPENED TO HAVE
PLANNED A MULTISITE CLINICAL
TRIAL CAN LEVERAGED THE
LOGISTICS CAPABILITIES OF THE
BDP FOR CELL THERAPY
DISTRIBUTION PRODUCTS AND SO WE
HAVE THE 3 GRANTEES LISTED HERE,
MASSACHUSETTS GENERAL IS
DEVELOPING A CAR TSTRATEGY THAT
TARGETS MESOTHELIUM AS WELL AS
EXPRESSING A DUAL TARGETING
AGENT THAT TARGETS FIBROBLASTS
ACTIVATING PROTEIN AND CD3 TO
RECRUIT BI STANDERS T-CELLS,
BEATRIZ CARRENO, HAS AT THE
UNIVERSITY OF PENNSYLVANIA, HAS
A VERY CHALLENGING PROJECT THAT
INVOLVES TCR T-CELL STRATEGY
TARGETING USING MKRAS, AND THE
HLA 1101 AND IT INVOLVES CRSPR
BASE YEEN KNOCK OUT AS WELL AS
YET TO BE DETERMINED EXHAUSTION
MARKER KNOCK OUT AND
INTORPERATION OF A MYELOID CHECK
POINT INHIBITOR OF THE FORM OF
AN FCFV, SO THIS 1 WILL BE
XROAMLY CHALLENGING FOR THE
PROGRAM AND THEN LAST BUT NOT
LEAST IS A RECENT FUNDED GRANTEE
PRASAD, ADUSUMILLI, WITH
MEMORIAL SLOAN KETTERRING, THIS
IS DEVELOPING A CAR SPECIFIC
MESOTHELIN, AND INCORPORATING CO
STIMLATTORY FACTORS AS WELL AS
PD1 DOMINANT NEGATIVE RECEPTOR
AND EXPRESSION FOR CHECK POINT
BLOCKADE, BUT THE REQUIREMENT
FROM THE ICN CORE AND THE BDP
FOR THIS IS JUST THE VIRAL
VECTOR THAT'S USED FOR
EXPRESSING THE CAR CONSTRUCT.
SO THE BDP TASK AREAS THAT ARE
PART OF THIS ICN CORE INCLUDE
GUIDANCE ON QUALITY SYSTEMS AND
REGULATORY AFFAIRS, INCLUDING
THE DEVELOPMENT AND
STANDARDIZATION OF ASSAYS FOR
DETERMINING PRODUCT CRITICAL
QUALITY ATTRIBUTES, PROVIDING
REAGENTS AND SOPs TO THE NET,
AND PROVOIDING REGULATORY
GUIDANCE, TIMES IN THE FORM,
MAYBE IN THE FORM OF GMP AUDITS
OR,A CYSTANCE WITH REGULATORY
FILINGS.
BUT THE--REALLY THE MEAT AND
BONES OF THE SUPPORT HERE COME
FROM THE CAPABILITY TO SUPPORT
MULTITRIAL GMP PRODUCTION,
INCLUDES DEVELOPMENT OF THE
NOVEL PRODUCTION TECHNOLOGIES
AND VIRAL VECTORS AND CELL
PRODUCTS FOR THE MULTISITE
TRIALS.
OKAY, SO ACCESS TO THE BDP FROM
THE INTRAMURAL COMMUNITY IS FROM
THE NCI DEVELOPMENTAL
THERAPEUTICS PROGRAM OR NEXT,
AND UNFORTUNATELY I WON'T GO
INTO DETAILS ON THE ADC THAT
DR. RATHMELL, MENTIONED EARLIER
BUT THIS IS THE MECH INFORM BY
WHICH THAT PROJECT IS IN THE
PORTFOLIO THROUGH THE NEXT PART.
SO NEXT A LOT OF FOLKS HERE ARE
FAMILIAR WITH IT'S NOT A GRANT,
NO FUNDED IS PROVIDED TO THE
APPLICANT, RATHER IT ALLOWS
APPLICATIONSLICANTS ON ACCESS TO
OUR RESOURCES HERE INCLUDING THE
BDP, IT DOES REQUIRE A CLEAR
PATH TO THE CLINIC OR PATIENT
BENEFIT AND THE APPLICANT
BECOMES A KEY MEMBER OF THE
PROJECT TEAM AND INVOLVED IN THE
PLANNING AND IMPLEMENTATION AND
ALSO HOUSE GETS FULL ACCESS TO
THE DATA GENERATED BY OUR
CONTRACTORS ISSUES THE NEXT
PROGRAM ALSO OFFERS A
PRECONSULTATION SERVICE NOT ONLY
TO PERSPECTIVE APPLICANTS ABOUT
YOU TO ANYBODY WHO IS IN THE
EARLY STAGES OF I& D PLANNING
AND NEEDS GUIDANCE ON WHAT KINDS
OF TOXICOLOGY STUDIES, SOME MAY
BE REQUIRED, TESTING FOR THE
CLINICAL PRODUCT AND THAT SORT
OF THING, SO IT'S BEEN A VERY
SUCCESSFUL SERVICE THAT'S MADE
AVAILABLE THROUGH THE NEXT
PROGRAM.
ALL RIGHT, I WANT TO HIGHLIGHT
THE RECENT COLLABORATIONS THAT
THE BDP HAS HAD WITH VARIOUS
ENTITIES, YOU KNOW 1 THING
THAT'S--THAT BCTD SUPPORTS WITH
THE REST OF NCI AND NIH IS THAT
WHEN THERE'S EXCESS CAPACITY
OUTSIDE OF DCT, PRIORITIES HERE,
THAT THE BDP CAN BE ACCESSED BY
OTHER AGENCIES, OTHER INSTITUTES
AND HAVE HAD A NUMBER OF
COLLABORATIONS WITH NCATS AND
CCR, AND DIVISION CANCER BIOLOGY
ANDY PREVENT PROGRAM TO DEVELOP
SOME OF THEIR AGENTS FOR THEIR
EXTRAMURAL COLLABORATORS.
SO 1 OF THE RECENT SUCCESSES
WE'VE HAD IS WITH
YEFERSON--JEFFERSON JEFF KOWENE
HAD A NOVEL EBV VACCINE
CANDIDATES ARE 2 CANDIDATES
THESE ARE BASED ON THE NANO
PARTICLE THAT CAN BE
IBT--INTEGRATE CORPORATED WITH
ANTIIENS AND IN HIS CASE HE WAS
ABLE TO SUCCESSFULLY INCORPORATE
THE EGP3 FICT ANTIGEN AS WELL AS
COMBO ANTIGEN EBV GHGLGP42, BUT
BEFORE THAT THE PROJECT TARTED
EARLIER IN PROCESS DEVELOPMENT
AND SCALE UP AND NEVER
MANUFACTURING AND ANALYTICAL
DEVELOPMENT, THE BDP PRODUCED
BOTH OF THESE PRODUCTS AS WELL
AS THE CLINICAL TRIAL AND
CURRENTLY THE EBC 350 AND IN
CLINICAL TRIAL ANDS ONCE SAFETY
IS DEMON TRAITED THERE, THE PLAN
IS TO INCORPORATE THE SECOND
NANO PARTICLE, THE GBHL32 FOR
CLINICAL TRIAL.
WE'VE ALSO STARTED A MEMORANDUM
OF UNDERSTANDING BETWEEN COREE
AND NCI, WE HAD A VISITOR FROM
THE KOREAN NATIONAL KANSZER
CENTER TO TOUR AND MEET WITH BDP
STAFF, THEY'RE VERY INTERESTED
IN GETTING UP TO SPEED ON CELL
THERAPIES AND CANCER VACCINES
TECHNOLOGIES AND SETTING UP A
DBP LIKE PROGRAM OVER THERE, SO
WE'VE ALREADY HAD A NUMBER OF
DISCUSSIONS WITH THE
REPRESENTATIVES, EXCHANGED A
NUMBER OF SOPs ALREADY AND
TALKING ABOUT POTENTIAL
COLLABORATIONS THAT MIGHT
INCLUDE A VISITOR COMING FROM
KOREA AND HOSTED BY THE DCTD OR
SERIES OF VISITORRING TO TAG
ALONG WITH THE BDP STAFF AND
UNDERSTAND HOW THE PROGRAM
WORKS.
BDP WAS ALSO INVITED TO
CONTRIBUTE TO THE HEALTH AND
ENVIRONMENTAL SCIENCES INSTITUTE
OR HESI, THEY'RE CELL THERAPY
TRACKS CIRCULATION AND SAFETY
COMMITTEE, CT-TRACKS THEIR
EFFORTS TO ADDRESS THE ISSUES
WITH REGARDS TO SAFETY AND
REGULATORY OR IPSC, OR INCLUESS
PLURIPOTENT STEM CELL THERAPIES
THAT ARE ON THE FOREFRONT.
AND THE BDP HAD EXPERIENCE WITH
IPSC, ASSESSMENT, DEVELOPMENT,
AS PART OF THEIR CRSPR-BASED
TECHNOLOGY DEVELOPMENT EFFORTS
IN RECENT YEARS AND SO IT'S BEEN
GENERATING SAFETY DATA IN ARE
ALIGNMENT WITH THE CT TRACKS
EFFORTS.
THEY ARE INCORPORATING THEIR
DIGITAL DROP OF PSR ASSAY, FOR
THE DETECTION OF
UNDIFFERENTIATED PLURIPOTENT
CELLS WHICH WAS IS A POTENTIAL
SIGNIFICANT SAFETY CONCERN FOR
THESE PRODUCTS IN THE FUTURE.
AND THEN, THE BDP AND US HERE IN
THE BRB AND ACT ARE INVOLVED
WITH NIST AND THEIR FLOW
CYTOMETRY CONSORTIUM.
THEY HAVE 2 WORKS GROUPS THAT
PERTAIN TO BDP ACTIVITIES, , THE
ASSAY GROUP FOR QUANTITATIVE
ASSAYS AND COMMONLY USED FOR
CELL AND GENE THERAPY AND GENE
DELIVERY SYSTEMS WORKING GROUP,
TO DEVELOP MEASUREMENT SOLUTIONS
AND STANDARDS FOR GENE DELIVERY
SYSTEMS BOTH VIRAL AND NONI HAVE
VALENTINED.
THE BDP, ALSO PROVIDES JUST
ABOUT ALL OF THEIR S. O. P.s,
THOSE THAT ARE NOT PRODUCT
SPECIFIC, ON THEIR WEBSITE, AND
THEY'RE FREE FOR DOWNLOAD,
THERE'S MORE THAN 300 SOPs FOR
MANUFACTURING, TESTING, QUALITY
SYSTEMS, CELL THERAPY THAT HAVE
BEEN ESTABLISHED AND HAD BEEN
VERY HELPFUL TO INDUSTRY AS WELL
AS ACADEMIC TRUSTEESS FOR
ESTABLISHING PROCEDURES AND
PROCESSES AND THEIR FACILITY.
AND THEN LASTLY, I WANTED TO
WIND UP THE PRESENTATION, TO
DESCRIBE A RARE OPPORTUNITY THAT
WE GET HERE IN BRB AND THE BDP
TO SEE SOME IMPACT THAT THE WORK
THAT WE DO HAS ON PATIENTS AND
YOUR COORDINATION OF SHAH AND
CRR AND [INDISCERNIBLE] IN MY
GROUP, WE WERE ABLE TO HOST A
VISIT BY 2 FAMILIES, THE
[INDISCERNIBLE] FAMILIES,
THEY'RE VERY ACTIVE FAMILIES FOR
PEDIATRIC CANCER RESEARCH AND
THE SANDY FAMILY VISITED WITH
THEIR SON, WHO IS THERE IN THE
CENTER PHOTO IN THE WHITE SHIRT
HERE, HE WAS ACTUALLY TREATED BY
NIRALI, AND SO TO BE ABLE TO
HOST THEM AND SHOW THEM HOW A
CAR T-CELL THERAPY IS MADE AND
WHAT GOES INTO THE TESTING AND
PRODUCTION OF IT WAS VERY
FULFILLING.
GAVIN LINDBORG, IS ALSO VERY
AVID ADVOCATE AND HIS SON EVAN
LOST HIS BALGT TO NEUROBLASTOMA
AND HE WAS VERY, VERY STRONG
CERTAINTIER OF THE BDP AND SO IT
REALLY PROVIDED US AND THE BDP
FOLKS WITH POSITIVE FEEDBACK
THAT WE DON'T NORMALLY GET FROM
ACTUAL THERAPY--ACTUAL OUTCOMES
OF THE THERAPIES THAT WE MAKE.
SO WITH THAT I WOULD LIKE TO
ACKNOWLEDGE THE BDP, THIS IS
JUST A PORTION OF THE BDP STAFF
THAT ARE INVOLVED IN THE
DAY-TO-DAY OPERATIONS HERE, MY
STAFF AND THE BRD, MICHELLE,
RAY, YEANY AND KASHA,
DR. DOROSHOW, AND STEVE,
HIGHFILL, AND THEY'VE ALL BEEN
VERY HELPFUL IN HELPING US STAND
UP OUR CELL THERAPY
CAPABILITIES.
NIRALI, AND RESOURCESY AND JEFF
WITH THEIR HELP FROM CCR AND
NIAID.
>> THANK YOU JASON WHAT AN
INCREDIBLE ARRAY OF THANKS THAT
YOU HAVE GOING ON FOR FOLKS
AROUND THE COUNTRY.
THANK YOU FOR THAT.
ANGELLA?
>> THANK YOU FOR THIS VERY COMP
REHONSIVE PRESENTATION, NOW WITH
THE SUCCESSES OF THE RNA
VACCINES AND ALL THE EXCITEMENT
ABOUT CRISPR TECHNOLOGIES, RNA
REALLY AS A BIOLOGIC IS MOVING
MORE INTO THE SPOTLIGHT, HAS THE
BDP CONTEMPLATED MOVING INTO
THIS SPACE.
ON YOUR PIE CHART, I REALLY SAW
ONLY A VERY SMALL SECTION AND
THAT WAS DEVOTED TO VECTORS, AND
60% PROTEINS SO WHAT ARE THE
PLANS?
>> WE ACTUALLY, WITHIN THE NEXT
PROGRAM, WE DO HAVE AN ACTIVE
PROJECT, IT IS RNA NANO PARTICLE
BASED THAT THE BDP IS
LEARNING--NOW WE DON'T HAVE THE
CAPABILITIES IN THE FACILITY
HERE FOR SYNTHESIZING RNA
CONSTRUBTS OR THE MATERIALS THAT
GO INTO DEVELOPING THE NANO
PARTICLES, BUT BECAUSE OF THE
BIOMEDICAL CAPABILITIES TO
SUBCONTRACT OR TECHNICAL
EXPERTISE, A LOT OF THIS WORK IS
BEING DONE OUTSOURCED AND WE'RE
IN EARLY STAGES OF THAT
PARTICULAR PROJECT BUT, YES, WE
ARE CERTAINLY MOVING INTO THAT
FIELD AND WE RECENTLY HAD A FEW
DISCUSSIONS WITH DR. SINGER ON
SOME OF THE NEED OUT THERE IN
THE COMMUNITY FOR RNA BASED
VACCINES AND THERAPY ANDS WE'RE
CERTAINLY WILLING TO COLLABORATE
WITH INVESTIGATORS AS THESE NEW
IDEAS COME IN.
>> I BELIEVE TIM?
>> YEAH, JASON THAT WAS A NICE
PRESENTATION.
MY QUESTION IS ACTUALLY BASED
OFF OF WHAT WAS JUST ASKED, AND
THAT IS, YOU KNOW FOR MY
INTERACTION WITH A FIELD SO FAR
AND PARTLY STIMULATED BY THE
SUCCESSFUL PARTY OF VACCINES, IS
THAT THE FACT THAT THERE'S A
CERTAIN LACK OF ACCESSIBILITY TO
DELIVERY VEHICLES NOW FOR
VACCINES AND ALL SORTS OF
RNAs.
IN FACT, YOU KNOW JUST FROM MY
KNOWLEDGE OF BEING ON VARIOUS
BOARDS AND STUFF, ACCESS TO
LIPID NANO PARTICLES ITSELF IS
OFTEN WRAPPED UP IN ALL SORTS OF
IP ISSUE ANDS THAT'S REALLY BEEN
A MAJOR, MAJOR ACHILLES' HEEL IN
PUSHING FORWARD A LOT OF
CLINICAL TRIALS, SO I'M
WONDERING IF YOU OR THE FNLAC
LEADERSHIP HAVE THOUGHT ABOUT,
YOU KNOW NOT JUST NANO PARTICLES
BUT OTHER TYPES OF PLATFORMS TO
ENHANCE ACCESS FOR THE FIELD
THAT SORT OF PERHAPS ALLOWS 1 TO
NOT BE SO WRAPPED UP IN TERMS OF
IP ISSUES AND SO FORTH.
>> YEAH, THE SHORT ANSWER IS
YES, WE HAVE CONSIDERED IT AND
IT'S BEEN A NUMBER OF
DISCUSSIONS.
I THINK THE CHALLENGE IS AND I
THINK THIS IS A BIGGER QUESTION
ON THE OUTSIDE OF MY OFFICE AND
THE BDP, BUT YOU KNOW IT'S LIKE
YOU SAID, HOW DO WE SET UP
WHETHER IT'S A CORE CAPABILITY
HERE AT THE FREDERICK NATIONAL
LAB OR A--LIKE I SPOKE AND WHEEL
TYPE OF MODEL WHERE IN THE
NATIONAL LAB SUPPORTS EXPERT
SITES TO PRODUCE THESE, BUT,
YEAH, YOU'RE RIGHT, THE IP ARE
VERY CHALLENGING.
I CAN TELL YOU WITH THE CURRENT
PROJECT THAT WE'RE WORKING ON, A
LOT OF THE LEAD TIME THAT WE'VE
SPENT IS IN ESTABLISHING THE
APPROPRIATE MTAs AND CDAs IN
PLACE SO THAT WE CAN ACCESS
THOSE, THOSE PROPRIETARY
REAGENTS AND IT HAS BEEN VERY
CHALLENGING.
>> RODNEY IN.
>> JASON YOU HAVE A BIG
FOOTPRINT, 66,000, SQUARE FOOT
AND 22,000 SQUARE FOOT IN
MANUFACTURING SO A LOT GOING ON.
SO THE CELL THERAPY, THE CELLS
AUTOLOGOUS, ARE ALL MOVING
FORWARD AND HEAVY ARE THESE
TOOLS AND QC, QA AND FACILITIES
AND PARAMOUNT EMPLOY IN TERMS OF
THE ACADEMIC RESEARCH OR
INSTITUTIONAL RESEARCH ON THE
PHASE 1 IS WITH THE SPACE OF THE
FNLAC WILL BE BOTH
[INDISCERNIBLE] AND NCI USE THAT
FACILITY TO ACCELERATE THE EARLY
CLINICAL STUDIES.
SO THE QUESTION REALLY IS THAT
HAVE YOU THOUGHT ABOUT GIVING
THE GOVERNMENT FACILITIES, AND
THAT'S ALSO GO TO NCI.
IT'S REALLY THE IP ISSUES IS 1
THING, ANOTHER IS GETTING ACCESS
TO IN OF THE REAGENT, RIGHT IN
SO ASSAY INSTITUTIONAL PRACTICE,
I THINK WE'RE CLEAR ON WHAT WE
CAN STUDY, EVEN THOUGH THERE
MIGHT BE RECONTRADICTIONS.
SO THE QUESTION IS HOW DO YOU
BALANCE BETWEEN SCIENCE
QUESTIONS VERSUS COMMERCIAL
INTEREST?
AND MAYBE IT'S FOR DR. RATHMELL,
TO CONSIDER EMPLOY YOU KNOW
THERE ARE ISSUES, OBVIOUSLY.
YOU CANNOT STOP US IF YEAR NOT
DEVELOPING ASSAY WORK, IF IT IS
HIGH PRIORITY FOR SCIENTIFIC
QUESTIONS, WE CAN THINK ABOUT A
WAY TO ADVANCE IT.
THAT'S FIRST QUESTION.
SECOND QUESTION REALLY IS COME
TO THE ISSUES OF ASSAYS TO YOUR
PROGRAM.
SO I UNDERSTAND THE ENTRY MAY BE
MIXED PROGRAM OR ANY OTHER ENTRY
THAT I'M NOT AWARE OF,
UNDERSTAND NCI HAS A NEXT
PROGRAM TO LOAD UP OTHER ISSUES
COULD BE THAT OF THE BIG
PROJECTS THAT WE TALK ABOUT,
RIGHT, GRANT-CHALLENGED PRODUCTS
HOW DO WE INTERFACE WHAT ARE THE
SAFE GUARD AND A LOT OF PEOPLE
ASK YOU HOW DO WE MANAGE THAT
ACCESS?
>> SO THAT IS A GREAT QUESTION,
A COUPLE IN THERE AND I WILL
MAKE AN ATTEMPT TO AT LEAST
PROVIDE, YOU KNOW MY PERSPECTIVE
ON SOME OF THOSE ASPECTS WITH
REGARDS TO THE BALANCING OF THE
SCIENCE WITH THE PRODUCTION, YOU
KNOW IT'S VERY EXPENSIVE, GMP
DEVELOPMENT PRODUCTION IS
EXTREMELY EXPENSIVE AND WHAT WE
HAVE TO BALANCE AT LEAST FROM MY
GROUP AND MY DIRECTIVE OF OUR
GROUP HERE IS THAT, YOU KNOW,
THE SCIENCE COMES INTO US PRETTY
MUCH WELL ESTABLISHED AND SO,
YOU KNOW OUR GROUP DOES NOT DO
THE--WE'RE NOT LOOKING AT
MULTILE CANDIDATES AND
CHARACTERIZING THOSE, WE REALLY
WANT TO FOCUS JUST ON THAT
VALLEY OF DEATH TRANSLATIONAL
PART OF THE DEVELOPMENT PROCESS.
SO THERE DEFINITELY NEED TO BE
OTHER FASSETS AND CERTAINLY THE
OTHER NATIONAL LAB CAN SUPPORT
THOSE FACETS OF THE SCIENCE
COMOPPOSITE BEHAVIORIAL
PHENOTYPENTS OF IT.
--COMPONENTS OF IT.
ONE MODEL THAT I THINK WILL WORK
OUT REALLY WELL IS THE CAN-ACT
INITIATIVE WHERE IT'S A
COMBINATION OF GRANT-FUNDED
RESEARCH WHERE THAT'S WHERE THE
SCIENCE OCCURS IS AT THESE
EN--STRATEGIESITUTES BUT THEN
THERE'S A VERY, VERY CLOSE
INTERACTION BETWEEN THE
TRANSLATIONAL COMPONENT HERE AT
THE BDP AND THEIR--YOU KNOW
THEIR SCIENTIFIC DEVELOPMENT SO
THAT IT WILL HOPEFULLY
TRANSITION VERY PATHOGENLY AND
QUICKLY INTO A CLINICAL TRIAL.
AND SO I THINK THAT THAT MIGHT
BE A REALLY GOOD MODEL FOR THESE
KINDS OF EFFORTS GOING FORWARD.
>> OKAY, I BELIEVE PLOSES ORDER
OF MICRONS, YOU HAD YOUR HAND U
P.
>> YEAH, THANKS.
YAISON THAT WAS AN AMAZING
PRESENTATION, KUDOS TO YOUR WORK
FOR ALL THIS.
I SAW A LOT OF CAR T-CELL WORK
BUT ARE YOU STARTING ANY CAR
IMPLEMENTATION TRIALS NWE WANT
TO BUT IT GETS BACK TO THE
PREVIOUS DISCUSSION, YOU KNOW
WE'RE DRIIVE MORE ON WHAT'S THE
NEED AT THE MOMENT.
SO WE WOULD HAVE LOVED TO HAVE
GOTTEN 1 OF THE CAN-ACT GRANTEES
THAT HAD A CART NK THAT WE COULD
WORK ON BUT THAT SPECIFIC NEED
EITHER THROUGH THAT MECHANISM OR
THROUGH THE NEXT PROGRAM, IT
HASN'T SURFACED YET BUT WE'RE
WILLING TO JUMP ON IT WHEN IT
COMES TO IT
>> BUT YOU HAVE THE FACILITIES
TO DO IT, IT'S JUST GROWING THE
DIFFERENT CELL TYPE IN.
>> ABSOLUTELY.
YES, IT'S GETTING FAMILIAR WITH
THE MARKERS AND ASSAY
DEVELOPMENT AND TYPES.
YEAH.
>> ALLYSON?
>> AWESOME.
IF I CAN FIGURE OUT HOW ON
UNMUTE MYSELF.
ANYWAY, JASON I'M REALLY EXCITED
ABOUT THE FACT THAT YOU FOLKS
ARE SUPPORTING EFFORTS THAT HAVE
CLINICAL TRIALS AT MULTIPLE
LOCATIONS.
THAT IS A TREMENDOUS KNOWLEDGE
IN TERMS OF SUPPLY CHAIN THAT
WILL BE REALLY IMPORTANT FOR THE
FIELD MOVING FORWARD, CAN YOU
COMMENT ON THAT A LITTLE BIT?
ARE YOU DOING A FAIR ARK MOUNT
OF FRESH IN, FRESH OUT,
CRYOPRESERVED IN HOW ARE YOU
ADDRESSING THE UNIQUE AND
IMPORTANT CHALLENGINGS OF
SCALING UP THESE THERAPIES TO
MULTIMEL CLINICAL SITES IN.
>> YES, THANK YOU.
THAT IS A GREAT QUESTION.
AND THAT IS 1 OF THE GOALS OF
THE CAN-ACT NETWORK AS WELL AS
STANDING UP THIS CAPABILITY IS
THE CENTRALIZED MANUFACTURING
AND LOGISTICS ESTABLISHMENT AND
VERY WELL CONTROLLED REPEATABLE,
ROBUST MANUFACTURING AND
ANALYTICAL PROCESSES.
SO, TO THAT END, WHAT WE'VE
STOOD UP SO FAR AND IT'S BEEN
SUCCESSFUL IS A CRYOPRESERVED
BASE LOGISTICS PROCESS WITH ALL
THE DOCUMENTATION AND THAT SORT
OF THING THAT'S BEEN VERY
SUCCESSFUL AND GRANTED THIS IS
JUST WITH CAR-T PROUCTS.
SO WE CAN HANDLE FROZENPHORESIS,
ACCORDING TO CERTAIN PROTOCOLS,
IT AM CANS OUT WELL, CELLS
TRANSDUCE WELL, THAT SAID,
THINGS MIGHT BE COMPLETELY
FLIPPED ON THEIR HEAD IF IT WAS
A DENDRITIC CELL BASED THERAPY
OR NK-CELL BASED THERAPY SO I
THINK WE WILL HAVE TO DEAL WITH
THAT BRIDGE WHEN WE GET TO IT.
>> YOU KNOW 1 THYME WE TALKED A
LOT ABOUT IN THESE ADVISORY
BOARDS AND HOW PEOPLE DON'T KNOW
ALL THE GOOD THINGS THAT ARE
HAPPENING AT THE FREDERICK
NATIONAL LABS AND IT WOULD BE
GREAT IF WE COULD HAVE SOME SORT
OF WORKSHOP OR SYMPOSIUM OR
SOMETHING JUST TO TALK ABOUT
SOME OF THESE CONTRIBUTIONS THAT
THE BDP HAS BEEN MAKING THAT I
THINK ARE IMPORTANT TO
DISSEMINATE.
JUST THROWING THAT OUT THERE.
BECAUSE THERE IS A LOT OF
EXPERTISE THAT COULD REALLY HELP
THE FIELD MOVE FORWARD AND THAT
MAY NOT BE GETTING OUT THERE.
>> GOOD POINT ALLYSON, SO
RODNEY?
>> SO I JUST WANT TO TACK ON TO
SAY THAT CELLS CNC,
MANUFACTURING AND PRESERVING
REENTRY REQUAL IIVES ALL THESE
ARE VERY, VERY IMPORTANT FOR THE
INDUSTRY MEMBERS, IT'S SO
IMPORTANT ABOUT QUALITY
ASSURANCE, AND SO HOW DO YOU
START THEM, HOW DO YOU VERIFY
ENTRY, AND SO ALL THIS KNOWLEDGE
CAN BE PUT TOGETHER FROM THE
CENTRAL LAB AS WELL AS THAT OF
INDUSTRY WHO WOULD BE WILLING TO
SHOW THOSE.
>> YEAH, I THANK YOU.
I AGREE AND THAT IS THE
INTENTION.
>> TIM IN.
>> JUST A QUICK QUESTION, JASON.
I THINK A YEAR AND A HALF OR 2
AGO WE HAD AN UPDATE ON THE
LEVEL OF UTILITY ON GMP VECTOR
PRODUCK, I KNOW IT WAS A VERY,
VERY HIGH DEMAND AT THAT POINT
AND WE WERE TALKING ABOUT IN
FNLAC A COMMITTEE ON HOW YOU
WOULD DEAL WITH THE INCREASE IN
DEMAND.
HOW IS IT GOING SO FAR?
I'M CURIOUS?
>> YEAH, YEAH, NO.
WELL.
THERE IS AGAIN A LOT OF CONTROLS
TO GET TO THE BDP, AND THE--THE
DEMAND AS FAR AS WE'RE HEARING,
NOT ONLY FROM THESE CAN-ACT
APPLICANTS BUT THE NEXT
APPLICANTS AND GENERAL
CONSULTATIONS THAT WE'VE
PARTICIPATED IN IS THAT YES, THE
AVAILABILITY TO GMP GRADE
RETROVIRUS LENTIVIRUS VECTORS,
EVEN NUCLEIC ACIDS, THE PLAZ
MIDS MIDS IN RNA AS YOU
MENTIONED EARLIER IS QUITE
STRAINED AND TO THAT EPPED, LIKE
I SAID, WE'VE GOT A COUPLE OF
SUITES HERE THAT ARE AVAILABLE
FOR MANUFACTURING, YOU KNOW, WE
CAN DO 2 PRODUCTS SAME
ULTIMATELY TAINIOUSLY IF WE HAD
THE APPROPRIATE THROW A FOOTBALL
SET UP FOR DOING THAT.
SO WE HAVE THE CAPABILITY TO
HELP ALLEVIATE SOME OF THIS NEED
IN THE COMMUNITY AND IN FACT,
JUST IN THE LAST YEAR, I THINK
WE MADE 2 OR 3ULENTYY VIRUS
PRODUCTS AND 1 OR 2 RETROVIRUS
PROD UBTS FOR OUR COLLABORATORS
IN THE NEXT PROGRAM OR OVER AT
CCR.
>> OKAY.
SO WE'RE NOW SCHEDULED FOR A
BREAK.
DO WE GO TILL DR. KANE--GIVE ME
SOME ADVICE, TO 2:50 OR SINCE
WE'RE AHEAD 2:45?
>> YEAH, I SUSPECT THERE MAY BE
A LOT OF INTEREST IN THE AI, SO
LET'S RECONVENE AT 2:45 P.M.
>> OKAY.
>> EASTERN TIME.
>> ALL RIGHT, SEE EVERYBODY
BACK.
SO NOW THESE WILL BE QUITE
INTERESTING, PRESENTATION ON AI
DRIVEN MULTISCALE INVESTIGATION
OF THE RAS-RAF ACTIVATION LIFE
CYCLE PROJECT, DR. STREITZ, AND
DR. NISSLEY,
>> THANK YOU, I WILL DO A QUICK
OVERVIEW, OF THE COLLABORATION,
WE ARE IN ITS SECOND YEAR OF 5
YEAR PERIOD, BETWEEN THE NCI AND
THE DOE.
THIS IS LAB RAARE TOYS NOT ONLY
WITH FNLAC AND AGERON, OAK RIDGE
AND LOS ALOE PHOSPHORYLATED,
NATIONAL LAB RAARE TOYS.
NOW THE 3 PROGGENTS WE WILL TALK
ABOUT TODAY ARE SHOWN ON THE
RIGHT IN CARTOON FORM, WHICH
FRED AND I WILL DESCRIBE AS
LOOKING AT THE MECHANISM OF AN
IMPORTANT BIOLOGICAL ACTIVITY
THAT ISN'T COMPLETELY
UNDERSTOOD.
IMPROVE IS AT A PRECLINICAL
SCALE AND THEN MOSAIC IS AT A
POPULATION SCALE.
AGAIN, PREDOMINANTLY AND I WILL
TELL YOU ABOUT OUR PROJECT
SHORTLY BUT THE IMPROVED PROJECT
AIMS TO EVALUATE IMPROVED DEEP
LEARNING MODELS OF DRUG RESPONSE
USING STANDARDIZED AND TESTING
DATA SETS AND THE MOSAIC PROJECT
APPLIES DEEP LEARNING MODELS AND
POPULATION BASED CANCER DATA,
THIS DATA SET TO--FOR
SURVEILLANCE AND ALSO TO MODEL
CANCER OUTCOMES IN REALTIME.
AND THEN A CROSS CUT, ACROSS
THESE--ALL THE NCI DOE PROJECTS
AND KNOWN AS CANDLE AND CANDLE
IS AN OPEN SOURCE DEEP LEARNING
METHODOLOGIES AND SET UP
CAPABILITIES, THAT'S AVAILABLE
ON GIT HUB AND HAS BEEN DESIGNED
AND ABLE TO WORK IN THIS TYPE OF
SPACE AND THAT WAS--CANDLE WAS
RECENTLY WON AN ARK WARD AS
SEVERAL OF THE CAPABILITIES THAT
WE'LL DESCRIBE AND THE OTHER
PROJECT TEAMS WILL DRIEB TODAY.
SO I WITHOUT FURTHER ADO, FRED
AND I WILL GET STARTED ON OUR
PROJECT.
>> GOOD AFTERNOON.
YOU'RE NOT IN PRESENTER DWIGHT.
>> OH, YOU'RE RIGHT THERE. WE
GO.
>> SO THE ADMIRAL PROJECT,
CLEVERLY NAMED AI DRIVEN
MULTISCALE INVESTIGATION OF
RAS-RAF ACTIVATION LIFE CYCLE,
THE POINT OF THIS PROJECT IS TO
INVESTIGATE THIS CRITICAL PIECE
OF BIOLOGY WITH A PIECE OF
TECHNOLOGY, A COMPUTING
TECHNOLOGY WHICH CURRENTLY
DOESN'T EXIST WHICH ENABLING US
TO JUMP BEYOND THE LIMITATIONS
OF CLASSICAL NORTH DYNAMICS AND
DYNAMICS THAT ARE LIMITED TO
PEEK SECONDS OR NANO SECONDS OR
MICROSECONDS, OR MILLI SECONDS
BUT THE BIOLOGY WE'RE INTERESTED
IN HAPPENS OVER SECONDS OR
MINUTES AND THIS IS AN ATTEMPT
TO BUILD THAT KIND OF CAPABILITY
WHERE YOU HAVE THE RESOLUTION
YOU WANT OVER THE TIME SCALE YOU
NEED.
AND THIS WAS TOAD UP WITH THE
NCEYE RAS INISSUIAATIVE WHICH WE
LEAD HERE AT THE FED RICK
NATIONAL LAB, AND THE GOALS OF
THAT WHEN THIS STARTED 10IERS
AGO, THERE WEREN'T ANY
THERAPEUTIC OPTIONS FOR CANCERS
THAT ARE RESPONSIBLE FOR 20-30%
OF CANCERS AND SOME OF THE--1 OF
THE GOALS OF THE PROGRAM WAS TO
DRIVE MECHANISTIC INSIGHTS INTO
THE BIOLOGY OF THIS.
SO WE'VE--YOU KNOW CAN PUT
TOGETHER A TEAM HERE THAT HAS
GENERATED LOTS OF DATA, STRONG
EXPERIMENTAL CAPABILITIES, SOME
OF THEM ARE SHOWN AT THE TOP AND
HAVE COLLABORATED WITH THE DOE.
>> SO [INDISCERNIBLE] BRINGS TO
THIS COLLABORATION, AND DOE, BUT
THEY BRING HIGH COMPUTING KALE,
AND ARGUABLILY THE PREMIER
COMPUTING STATION IN THE WORLD
AND CERTAINLY IN THE COUNTRY IN
TERMS OF THE MACHINE ANDS CAPE
ANLT THAT IS PRESENT THERE.
ALONG WITH MEAS MACHINES WHICH
ARE TYPICAL LYE A
MEDICAL--TYPICALLY A MILLION
TIMES MORE THAN THIS MACHINE,
THE PERSONNEL WITH ADVANCE TO
ACTUALLY UTILIZE THAT AND THEY
WILL BE USING THESE TIGHT COUPLE
WITH THE COLLEAGUES AT FREDERICK
TO DO MOLECULAR DISCIPLINARY
DYNAMIC
STIMULATION, TO VERIFY THIS
EXPERIMENT TO LOOK AT THIS
PARTICULAR RATHER DIFFICULT
PROBLEM IN RAS BIOLOGY.
>> AND SO JUST GOING QUICKLY
OVER THE BIOLOGY THAT WE'RE
STUDYING, THIS IS A CARTOON OF
THE RAS-RAF ACTIVATION AS WE
CALL TIT'S A MEMBRANE, - IT IS A
BINARY SWITCH WHEN ON, ENGAGES
EFFECTORS, THE PRIMARY EFFECTOR
OF MAP K-SIGNALING IS THE RAF
KINASE, IT EXISTS IN AN
AUTOINHIBITTED FORM AND THAT
AUTOINHIBITION IS RELEASED WHEN
COMPONENTS OF RAF KINASE
INTERACT WITH RAS AND
CONSEQUENTIALLY THE MEMBRANE
RESULTING IN SERIES OF
DEPHOSPHORYLATION,
REARRANGEMENTS WITH CHAPERON
PROTEINS KNOWN AS 1433
STRICTURAL CHANGES AND THEN,
CLUSTERING OR COLOCALIZATION OF
THE MEMBRANE SO THAT 2 RAFs
CAN DIMERIZE AT THE KINASE
DOMAIN AND RESULT IN AN ACTIVE
SIGNALING PLATFORM SO THAT THE
KINASE AND ACTIVATED AND SIGNAL
IS PROPAGATED DOWN THROUGH THE
CASCADE.
SO YOU KNOW WE'RE INTERESTED IN
THIS FOR BEYOND JUST THE BIOLOGY
ISSUES WE BELIEVE THAT MULTIPLE
STEPS HERE, THERE ARE
THERAPEUTIC POSSIBILITIES THAT
IF THE STRUCTURE AND THE
MECHANISM WERE UNDERSTAND
BETTER, WE MIGHT BE ABLE TO
EXPLOIT TO PERTURB ONCOGENIC
SIGNALING.
THE FIRST STAGE OF THIS PROJECT,
JUST THE FIRST 5 YEARS WAS TO
ACTUALLY BUILD A MODEL TO BETTER
UNDERSTAND RAS IN THE CONTEXT OF
A REALISTIC MEMBRANE, THAT WAS
REFERRED TO AS PILOT 2.
AND WHAT WE WILL WILL DESCRIBEU
TODAY IS WHAT FOLLOWED ON FROM
THAT.
BUT AS A PILOT IN THESE 2, WE
DID THESE SIMULATIONS IN THE 8
LIPID MEMBRANE, SCALE, MORE FOR
SIMULATION THAN HAD EVER BEEN
DONE BEFORE AND WAS BIOLOGICALLY
AND AT THAT TIMISTICALLY
RELEVANT EMPLOY WE IDENTIFIED
FINGERPRINTS OR CONCENTRATIONS
OF SPECIFIC LIPIDS AROUND RAS,
THIS IS JUST THE DENSITY
REPRESENTATIONS OF THE DIFFERENT
LIPIDS, AND RAS IS SHOWN HERE IN
BLACK, AND WE WERE ABLE TO
IDENTIFY FINGERPRINTS OR
CONFIGURURATIONS OF THE LIPIDS
THAT RAS PREFERRED OR RAS
CREATED WHEN IT AGGREGATED.
AND WE REFER TO THOSE AS LOW,
AVERAGE AND HIGH RAS FINGERPRINT
ANDS WE WERE ABLE TO
RECAPITULATE THAT EXPERIMENTALLY
SHOWN ON THE BOTTOM RIGHT BY
DOING SPR BIEBDING EXPERIMENTS
AND COULD SHOW THAT IF WE
RECONSITUTED THE LIPID
FINGERPRINTS THAT WERE
ASSOCIATED WITH HIGH RAS
BIEBDING OR ACCUMULATION OF RAS
AND ANTICLUSTERS WE COULD GET
STRONGER BINDING INVITRO.
SO AS I SAID AT THE OUTSET, 1 OF
THE THINGS WE NOTED AS WE WERE
FINISHING PILOT 2 AND HAVING
BUILT THAT CAPABILITY TO DO THE
HUNDREDS OF THOUSANDS OF
SIMULATIONS CORRELATED
SIMULATIONS THAT LED TO THE
RESULTS THAT DWIGHT JUST
PRESENTED IS THAT WE WANTED TO
BE ABLE TO GET MORE AROUND THE
ACTIVATION LIFE CYCLE THAT
DWIGHT DESCRIBES BECAUSE OF THE
TIME FRAME INVOEVERRED, MUCH
LONGER TIME, WE NEEDED A
DIFFERENT APPROACH, AND THAT
APPROACH IS ADMIRRALL, WHICH WE
WILL SPEND A BIT OF MORE TIME
SPEAKING ON BUT FIRST, A LITTLE
MORE CARTOON FORM.
>> THIS REPRESENTS THE PROCESS,
WHEN THAT RAS IS GDP BOUND IN
THE UPPER LEFT, IT'S INACTIVE
CONFIGURURATION, WHEN IT'S GTP
BOUND IT'S IN ACTIVE
CONFIGURURATION AND COMBINED 2
EFFECTORS SUCH AS THE RAS-RAF
KINASE, WHICH THE DIFFERENT
DOMAINS ARE SHOWN HERE.
ENGAGEMENT OF THE RAS BINDING
DOMAIN RBD RESULTS IN PARTIAL
LOOSENING OF THIS COMPLEX AND
EVENTUAL MOVEMENT OF THE CRD
INTO THE MEMBRANE AND YOU CAN
SEE THAT ASSOCIATED WITH THIS
BINDING TO RAS AND REARRANGEMENT
THAT THERE'S A RELEASE OF SOME
COMPONENTS OF RAF ARE OPENING
UP, THERE'S PROBABLY
DEPHOSPHORYLATION STEPS THAT ARE
ASSOCIATE WIDE THAT, BUT THERE'S
LARGE DOMAIN MOVEMENT, AND
REARRANGEMENT DOMAINS AND THESE
ARE THE TYPE OF THINGS THAT ARE
HARD TO CAPTURE EXPERIMENTALLY,
AND SO PART OF THE RATIONAL FOR
THIS PROJECT IS TO TRY TO MODEL
SOME OF THESE THINGS
COMPUTATIONALLY, AND THEN
ASSOCIATE WIDE THAT, WE HAVE
INPUTS SUCH AS STRUCTURES THAT
WE'VE GENERATED HERE WITHIN THE
RAS INITIATIVE OR NCI, THIS JUST
SHOWS R,A S BOUND TO THE RBD AND
CRD OF THE RAF KINASE, WE HAVE A
PLETHORA OF EXPERIMENTAL
APPROACHES, YOU KNOW INCLUDING
LOOKING AT SIGNALING IN LIVE
CELLS, TO LOOK AT BINDING AND
ACTIVATION OF DEFINITE ONCOGENIC
MUTANTS OF RAS OR PERMIAITATIONS
OF RASE MODEL BETWEEN DIFFERENT
RASs AND RAF, AND WHAT HELPED
EARLIER THAT WAS GENERATED
EENTLY WITHIN THE LAST YEAR OR 2
THAT CAME OUT OF THE MORRISON
LAB AND CCR THAT SHOWED THIS
AUTOINHIBITTED COMPLEX SHOWING
DOWN AT THE BOTTOM 1433, AND
THEN THE RAS BYPASSING DOMAIN
AND THE CRD DOMAINS ALONG WITH
THE KINASE DOMAIN IN THE
INHIBITING COMPLEX, AND HELPFUL
IN PUSHING US FORWARD, SOME
EXPERIMENTAL APPROACHES JUST TO
SHOW HOW WE INTEND TO YOU KNOW
IN PARALLEL VALIDATE PREDICTIONS
FROM THE STIMULATIONS ARE SHOWN
ON THE LEFT.
AND THAT AN AUTOINHIBIT THE
COMPLEX APPOINTED BINDING TO
RAS, ITSELF, WILL COME UP
WITH--WELL, WE WON'T WORRY ABOUT
THAT FOR NOW.
IF RAF BINDS TO RAS AND RELEASES
2 FLOORS INDICATED HERE WITH A
GREEN AND RED STAR WOULD MOVE
FURTHER APART AND IF YOU SET
THOSE UP SO THAT THOSE WERE SET
UP FOR FLUORESCENCE ENERGY
TRANSFER OR FRET, YOU CAN
IMAGINE THAT SIGNAL WOULD
CHANGE.
SO THAT'S 1 WAY WE COULD LOOK AT
ACTIVATION OR DOMAIN MOVEMENT.
WE ALSO HAVE THE ABILITY TO
COLLABORATE WITH OTHERS AND LOOK
AT THE NEUTRON REFLECTIVITY
SHOWN HERE ON THE RIGHT.
IN THE BUT TITLED PANEL, YOU SEE
THE EXPECT RUM YOU GET FROM RAS
WHEN IT'S SITTING ON A MEMBRANE
WHICH IS SIDE WAYS IN IN DIAGRAM
AND THERE'S AN AVERAGE DISTANCE
TO THIS CENTER TO THE MOLECULE,
WHEN YOU ADD RAFOT LEFT, CAN YOU
SEE THAT RAS MOVES CLOSER TO THE
MEMBRANE AND WE CAN NOW SEE
DENSITY THAT'S ASSOCIATE WIDE
THE RAF KINASE ITSELF, SO THESE
ARE JUST EXAMPLES OF SOME OF THE
MANY TYPES OF EXPERIMENTAL
APPROACHES WE HAVE TO LOOK AT
THIS IN PARALLEL WITH THE
COMPUTATIONAL APPROACHES.
>> SO I HOPE YOU CAN APPRECIATE
HOW DIFFICULT SOME OF THE
EXPERIMENTS ARE IN ORDER TO GET
WHAT IS SOME OF THE BASIC PIECES
OF INFORMATION, LIKE THE
STRUCTURAL COMPONENTS BUT WE
WANT TO FIND OUT THE DYNAMICS,
WE WANT TO SEE HOW IT GETS FROM
THE FIRST STATE, WHAT I WILL
CALLITATE A, MARKED WITH THE
LEFT ARROW THERE, TOITATE B, THE
RIGHT ARROW AND THESE ARE STATES
THAT WE CAN ACTUALLY HAVE
EXPERIMENTAL CONFIRMATION FROM,
THE WORK THAT DWIGHT JUST
DESCRIBED.
HOW DOES IT GET FROM THERE, FROM
1 TO THE OTHER.
THIS IS WHAT WE CAN'T MODEL WITH
THE SINGLE DYNAMIC SIMULATION,
IT'S TOO LARGE, EVEN FOR THE
LARGEST COMPUTER ON EARTH, IT'S
TOO LARGE, SO THE APPROACH WE'RE
TAKING MOW IS USING MACHINE
LEARNING TO DEVELOP A SUITABLE
LATENT SPACE AND A LATENT SPACE
IS A REDUCED ORDER SPACE, LOWER
DIMENSIONAL SPACE.
YOU COULD THINK OF THAT AS LIKE
TAKING A PHOTOGRAPH OF 3
DIMENSIONAL SCENE AND THEN
CAPTURING THAT ON A 2
DIMENSIONAL PIECE OF FILM,
THAT'S SORT OF--THAT'S A FUNNY
WAY SORT OF LIKE A LATENT SPACE.
ONE THING WE CAN DO WITH CERTAIN
TYPES OF LATENT SPACES AND
YOU'VE SEEN A LOT OF THIS
WRITTEN ABOUT IN THE OPEN PRESS
IS YOU CAN ONCE YOU FIGURE OUT
HOW TO CREATE A SPACE, YOU CAN
PLAY IT BACKWARDS WHICH MEANS
YOU CAN TAKE A SPOT IN THE
LATENT SPACE AND TURN IT INTO A
CONFIGURURATION, YOU CAN DO
GENERATIVE WORK.
SO THE INTENT HERE IS FOR US TO
LEARN A LATENT SPACE THAT HAS A
CLUSTER IN THAT SPACE THAT
REPRESENTS THE FIRST STAGE WHICH
IS HERE SHOWN, RED, AND THAT
REPRESENTS THE SECOND STATE
WHICH IS HERE SHOWN ORANGE.
WE DON'T KNOW WHAT HAPPENS IN
THE MIDDLE BUT RATHER THAN TRY
TO EXPLORE THAT IN REAL SPACE,
USE THE LATENT SPACE TO
GENERATE, GO INTO THE NEXT
SLIDE, SO WE WILL SET UP A LOOP
THAT ATTEMPTS--ATTEMPTS A NEW
CONFIGURURATION, VALIDATES IT
WITH THE HIGH PERFORMANCE
DYNAMICS CODE AND IF IT'S GOOD
WE KEEP IT AND IF IT'S NOT GOOD,
WE DON'T KEEP IT AND IF WE KEEP
DOING THIS LOOP, SO IN THIS WAY,
WE LEARN NOW DOTS AND NEW SPACES
IN THE LATENT SPACE WE DIDN'T
KNOW BEFORE, THESE WERE VALID
CONFIGURATIONS AND IF WE
CONTINUE THIS LOOP, WE WILL FILL
THIS SPACE IN THE LATENT SPACE
BETWEEN THE 2 FIGURURATIONS, THE
FOLDED AND THE UNFOLDED STATE
AND WE CAN PAUSE IT NOW A PATH
THAT CONNECTS THISEMMA WE
COULDN'T HAVE SEEN SINGLY BUT
NOW WE KNOW WHERE THE PATH IS,
WE HAVE A REACTION COORDINATE
AND WE CAN GO BACK AND VALIDATE
THAT TRAJECTORY.
GO AHEAD AND GO TO THE NEXT
SLIDE.
THIS IS BUILDINGOT TECHNOLOGY WE
CREATED OUT OF PILOT 2 TO
INITIATE, RUN, ANALYZE, CLOSE
AND YOU KNOW HARVEST THE DATA
FROM LITERALLY HUNDREDS OF
THOUSANDS AND WE'RE XEBTING
CLOSE TO A MILLION STIMULATIONS
IN ORDER TO DO THE PROCESS THAT
I JUST DESCRIBED TO YOU.
ALL OF THAT HAS TO GET MAPPED ON
TO A VERY COMPLICATED COMPUTER,
ALL THE DAILY BASIS THEA HAS TO
BE THE RIGHT SPOT AT THE RIGHT
TIME AND THAT'S ALL MANAGED WITH
WHAT WE CALL MIMI, OUR
MULTISCALED MACHINE LEARNING
MODELING INFRASTRUCTURE THAT
WE'VE NOW UPGRADED TO FIT INTO
THIS GENERATIVE MODELING WE'RE
USING FOR ADMIRRAL.
OKAY, YES, YEAH, NO, GO BACK 1
PLEASE, AND I'LL EXPLAIN JUST A
LITTLE BIT MORE HOW THIS WORKS.
BECAUSE YOU SEE THE PINK, BLUE,
GREEN AND PURPLE ARE DIFFERENT
LAYERS IN THE MODEL.
THE PINK LAYER IS THE COURSES
SAMPLE AND THAT'S WHERE WE'RE
ACTUALLY GENERATING PROTEIN
CONFIRMATIONS THAT WE'RE GOING
TO VALIDATE.
THE BLUE MODEL INCORPORATES THE
LIPID AROUND THE PROTEIN
CONFIRMATION WHICH IS JUST A
GUEST, NOW WE WILL PUT A LIPPED
AROUND IT AND NOW WE WILL MODEL
IT USING COARSE GRAIN SIMULATION
FULLY ANIMALISTIC MODELS WITH
THE CORE KREEN WHERE THE CORE
SCREEN MAY NOT BE COMPLETELY
CORRECT AND THEN THAT
INFORMATION GETS FED BACK UP AND
YOU RATHER, RINSE, REPEAT AND
YOU DO IT OVER AND OVER AGAIN AS
YOU FIND THE SPOTS THAT ALLOW TO
YOU CONNECT THE PATH THAT YOU
WOULD NOT HAVE EVER SEEN, THAT'S
ADMIRAL IN A NUT SHELL.
THE CODE IS BASED ON THIS MEDIA
FRAMEWORK AND A NUMBER OF VERY
SPECIALIZED CODES THAT HAVE BEEN
WRITTEN TO HANDLE THIS PROCESS,
THEY'RE ALL HIGHLY SCALABLE
CODES AND THEY'RE ALL AVAILABLE
OPEN DOMAIN, THE MUMMI
FRAMEWORK, THE DDCMD, THE
MULTIDISCIPLINARY MEDICARE AND
MEDICAIDICS CODE, MAR TIPY
PARAMETERS WHICH WE CAN COLLAB 8
WITH THE FOLKS WHO DEVELOP THE
MARTINI PARAMETERS, ALL THE WAY
TO THE CODE THAT IS USED TO DO
THE MANAGEMENT OF THE COMPUTER
ITSELF, ALL OF THAT IS OPEN
DOMAIN.
>> IN ADDITION MUCH OF THIS DATA
HAS BEEN PLACED ON THE CANCER
.GOV SITE AND IT'S A SITE THAT'S
SET UP FOR ALL THESE
COLLABORATIONS OR PROGECS TO
SHARE DATAS AND CAPABILITIES.
THIS HAS BEEN A HIGHLY
COLLABORATIVE INTERACTIVE
PROJECT MULTIDISCIPLINARY ACROSS
MULTIPLE LABS AND INITYS, I
THINK IT'S BEEN A REAL BOOM FOR
THE FNLAC AND TO INTERACT WITH
PEOPLE FROM LIVER MORE WHO ARE
MORE COMPUTATIONALLY BASED.
>> IT'S BEEN AN EXTRAORDINARILY
COLLABORATIVE PROCESS, WHICH MET
THE PREMISE OF THE ORIGINAL
PROJECTS WHICH WAS THAT THE D.
O. E. WAS GOING TO BRING VERY
HIGH PERM FORMANCE COMPUTING TO
HELP WITH THE DEEP COMLICATED
BIOLOGY THAT NCI IS DEALING WITH
AND THE CHALLENGING BIOLOGY IS
GOING TO INFORM AND COMPUTE IN
THE D. O. E. AND I THINK BOTH OF
THOSE HAVE HAPPENED.
NAGREED AND JUST 1 FINAL SIDE,
TO REMIND EVERYONE THAT BIOLOGY
IS COMPLICATED AND WHAT WE TOLD
YOU ABOUT TODAY, YOU KNOW IS
JUST A COMPONENT OF THIS, RAS
AND RAF INTERACTION BUT THERE
ARE MANY OTHER THINGS THAT COULD
BE MODELS WITH PERMIAITATIONS OF
THIS SYSTEM AND WE LOOK FORWARD
TO CONTINUING TO DELVE INTO THIS
AND FIGURE OUT WHAT WE CAN ABOUT
CANCER BIOLOGY AND ONCOGENIC
SIGNALING, SO THANK YOU FOR YOUR
TAME AND I THINK WE'LL TAKE
QUESTIONS.
>> THANK YOU.
>> GREAT PRESENTATION.
DO WE HAVE QUESTIONS?
>> I HAVE A QUESTION.
ANAT HERE.
>> YES.
>> GREAT, WONDERFUL
PRESENTATION.
THIS QUESTION IS PROBABLY FOR
FRED, SO I GUESS 2 QUESTIONS I
HAD, 1 WAS WITH REGARD TO THE
LATENT SPACE, HOW DO YOU
IDENTIFY WHAT IS THE APPROPRIATE
DIMENSIONALITY WITHIN WHICH TO
DO YOUR SIMULATION OR APPLY THE
LEARNING AND THE SECOND QUESTION
IS, HOW DO YOU MEASURE SUCCESS
FOR THIS KIND OF SIMULATION
BASED EXPERIMENT, THANK YOU.
>> SO THE FIRST 1 I WILL GIVE A
HAND WAVY ANSWER, BECAUSE I
MYSELF DID NOT DO THAT
CALCULATION, BUT, THERE IS AS
THEY BUILD THE LATENT SPACE,
THEY TRY VARIOUS MODELS AND YOU
WANT OF COURSE THE SMALLEST
MODEL YOU CAN GET AWAY WITH
BECAUSE THE TIME FOR TRAINING
GOES UP SUBSTANTIALLY WITH HOW
LARGE A MODEL YOU HAVE, SO IF
IT'S TOO SMALL A MODEL, IT
DOESN'T CONVERGE AND YOU CAN'T
ACTUALLY GET, YOU KNOW--YOU
CAN'T GO BACK AND THE OUTER
DOESN'T CONVERGE, YOU CAN'T COME
BACK AND GET YOUR PREDICT
BACKWARDS WITH WHAT YOU STARTED
WITH.
IF YOU HAVE A LOT OF PARAMETERS,
YOU CAN GET THE RIGHT ANSWER,
YOU CAN IN FACT INVERT YOUR
AUTOENCODER BUT YOU'RE TAKING
TIME BUT IT'S EXPERIMENTAL
PROCESS, BASICALLY BUT YOU FIND
THE SPOT THAT WORKS, THAT IS
SMALL ENOUGH THAT YOU CAN DEAL
WITH AND THAT'S SORT OF HOW THAT
PROCESS IS DONE.
TO ANSWER YOUR OTHER QUESTION OF
HOW YOU CAN--HOW CAN YOU BE
SURE, WHAT'S YOUR CONFIDENCE
BASICALLY THAT YOU WILL WIND UP
WITH A RIGHT ANSWER, HOW DO YOU
VALIDATE THIS, THERE ARE 2 WAYS.
FIRST OF ALL WE'RE VALIDATING
THE CONFIRMATIONS AS WE'RE
DEVELOPING THEM, THAT'S PART OF
THAT WHOLE LOOP I DRIEBED TO
YOU, WE WILL DO THAT ON THE FLY.
AND BY THE WAY, AS WE'RE FINDING
THOSE SAMPLES, WE'RE RETRAINING
A LATENT SPACE, SO THAT LATENT
SPACE GETTING MORE AND MORE
INFORMED AS WE'RE GOING ALONG.
BUT THE FINAL PROOF AT THE VERY
END, IF WE HAVE A VALID
TRAJECTORY, THAT MEANS WE HAVE
ALSO DEFINED A VALID REACTION
COORDINATE AND NOW WE CAN RUN A
SINGLE MOLECULAR DISCIPLINARY
DYNAMIC
SINGULATION AND DRIVING THE
REACTION COORDINATE THAT GOES
ALL THE WAY ACROSS, EVEN IF
THAT'S SECONDS OF TIME, WE CAN
DO THAT, WE CAN DRIVE THE
DYNAMICS SIMULATION AND VALIDATE
IT'S A CORRECT TRAJECTORY.
IF THAT DOESN'T WORK, WE GO BACK
AND DO THE WHOLE THING AGAIN
BECAUSE IT'S POSSIBLE WE DO
SNAPSHOTS THAT ARE NOT IN FACT
CONNECTED TO TRANSLATIONAL
RESEARCH YECTRY, WE BELIEVE IT
WILL CONVERT BUT THAT IS THE
ONSLAUGHT OF THE PROJECT THAT
WILL DELIVER A TRAJECTORY THAT'S
VALID.
NTHANK YOU N.
>> CAROL?
>> YEAH, GREAT PRESENTATION AND
I'M WONDERING ABOUT THE
MACROMODEL PARAMETERS AND SO
HAVE YOU THESE PARAMETERS, YOU
BUILD IN THIS MODEL AND DO YOU
THEN GO BACK AND SEE WHICH ARE
THE MOST INFORMATIVE PARAMETERS,
I MEAN COULD YOU BUILD A MODEL
WITH FEWER PARAMETERS AND GET
THE SAME OUTPUT SO THAT CAN YOU
STREAMLINE THIS A LITTLE BIT
MORE OR HOW DO YOU GO ABOUT THE
MODEL PARAMETER SELECTION, I
GUESS, IS MY QUESTION AND CAN
YOU MINIMIZE IT?
NWE TRIED TO MINIMIZE IT BECAUSE
THE PARAMETERS BECOMES EXPENSIVE
QUICKLY, AND EVEN THOUGH WE HAVE
LARGE COMPUTERS IT GETS REALLY
EXPENSIVE.
SO YOU SAID MACROMODEL, SO
THAT'S A VERY SPECIFIC THING.
NYEAH, YEAH, YEAH.
>> THAT'S WHAT WE USE TO EQUILL
LIBRARY FOUNDATIONATE THE
LIPIDS, IT'S PUBLISHED, IT'S A
THEORY BASED MACROMODEL THAT IS
RIGOROUSLY BASED ON CORRELATION
FUNCTIONS THAT HAVE COME OUT OF
MOLECULAR DYNAMIC SIMULATIONS.
SO THAT'S TAKEN DIRECTLY.
SO WE RUN THOUSANDS OF
SIMULATIONS, CORRELATION,
COENTIOUS FICIENTS AND THOSE
WIND UP DRIVING A MA ROUGH ATOM
MODEL WHICH IS WHERE WE
CALIBRATE THE LIPIDS BASED ON
THE PROTEIN CONFIGURATIONS.
>> SO HOW EXTENSIBLE--ARE YOU
ANYTHING TO HAVE TO GO THROUGH
THIS WHOLE PROCESS FOR EXTENDING
THIS APPROACH TO LIKE ALL THAT
OTHER SPACE OF INTERACTION
THATION WERE SHOWN ON THE LAST
SLIDE OR THINGS THAT YOU CAN
BORROW.
>> MACHINERY CAN BE BORROWED,
THE PARAMETERS WOULD ALL BE
DIFFERENT.
SO THERE'S NOTHING, THERE'S
NOTHING--SPEAKING AS A
COMPUTATIONAL PHYSICIST, WHAT WE
HAVE BUILT IS A FRAMEWORK FOR
DOING A MULTISCALE MODEL ON AN
EXTRA SCALE COMPUTER.
WE CAN DO THIS ON A NUMBER OF
DIFFERENT BIOLOGY CONTEXT, A
NUMBER OF DIFFERENT PHYSICS
CONTEXT, IF YOU WANT A DIFFERENT
SET OF LIP I EDUCATIONALS, WE
COULD RUN SIMULATIONS, WE COULD
DO THAT PARAMETERIZATION AND WE
COULD BUILD ON A DIFFERENT SET
OF MODEL FOR A DIFFERENT SET OF
LIPIDS BUT WE HAVE THAT
MACHINERY IN PLACE NOW.
>> THANK YOU.
>> I BELIEVE RODNEY.
>> THANK YOU FRED AND DWIGHT.
I THINK THAT'S EXACTLY WHAT AI
WOULD BE VERY USEFUL FOR AND
THEN WITH THE COMPUTING POWER SO
I'M VERY FLAD --GLAD YOU HAVE AL
DEFINED PARAMETER YOU'RE LOOKING
AT.
IT'S COMPLICATED ENOUGH WITH
LIPIDS, TELL BE HUGE, RIGHT IN
SO THE SIMULATIONS OF ALL THE
SPACE, VERY SMALL FRAMEWORK IS
GOING TO TAKE A LOT OF
COMPUTING, SO THERE ARE A COUPLE
THINGS THAT I WAS TRYING TO
FIGURE IS THAT IN ADDITION TO
THE COMPUTING POWER, HAVE YOU
LOOKED AT POSSIBLITY OF QUANTUM
COMPUTING AS A NEXT STEP TO
ACCELERATE SOME OF THESE
PROCESS?
I KNOW LIVER MORE AND OTHER
PLACES ARE LOOKING AT IT AND
THAT'S 1 QUESTION.
ANOTHER QUESTION IS THAT JUST
RELATED TO US ABOUT THE
EXCHANGING LIPIDS.
SO THERE ARE SOME LIPIDS THAT
MAY CHAISM YOUR DYNAMICS ABOUT
HOW PROTEINS SIT IN THERE, AND
THE IN TERMS OF THE NANO OR
PARTICLE SECOND DIRECTIONS MAY
CHANGE.
SOPHISTICATEDY THAT IS A GOOD
PLACE TO BE IN, THE QUESTIONS
REALLY IS GOING TO COME TO IT,
AT LEAST IN MY MIND IS HOW DO
YOU VALIDATE THESE?
YOU KNOW ONCE YOU HAVE THESE
PARAMETER AND THEY WILL BE NEED
TO BE SOME SORT OF EXPERIMENTAL
VALIDATIONS TO FOLLOW UP TO TEST
YOUR MODEL.
>> ABSOLUTELY.
SO I WILL ANSWER THE QUANTUM
QUESTION AND I WILL LET DWIGHT
ANSWER THE VALIDATIONOT LIPIDS
QUESTION.
SO, YES, WE HAVE THOUGHT ABOUT
QUANTUM COMPUTING AND YOU'RE
RIGHT, THERE IS A FAIR AMOUNT OF
WORK GOING ON HERE AT LIVER
MORE.
WE ARE NOT AS PART OF THIS
PROJECT TRYING TO DEVELOP A
QUANTUM ALGORITHM THAT WE COULD
UTILIZE AND THAT'S REQUIRED, I
THINK THAT QUANTUM COMPUTING, I
WOULD SAY IS NOT QUITE READY FOR
PRIME TIME YET.
OT OTHER HAND I THINK IT IS
CLOSE.
IT'S A PERFECTLY REASONABLE
THINK TO BE EXPLORING.
THAT WOULD BE OUTSIDE THE SCOPE
OF WHAT WE'RE DOING IN THIS
PROJECT BUT I THINK THAT
POTENTIALLY SOME OF THE--BOTH
SOME OF THE MACHINE LEARNING,
OPTIMIZATION AND ACTUAL
SIMULATION COULD BE PROFITABLY
ACCELERATED WITH A FUNCTIONING
QUANTUM COMPUTER, THAT SHOULD BE
EXPLORED.
>> AND IN TERMS OF YOUR QUESTION
OF VALIDATION AND LIPID PROTEIN
INTERACTIONS, WE DEPARTMENT HAVE
TIME TO GO INTO GREAT DETAIL BUT
AS PART OF PREVIOUS ITERATION OF
THIS PROJECT WE DEFINED AN 8
LIPID COMPONENT MEMBRANE THAT
WAS BRACED ON THE PRESENCE OF
LIPIDS IN CELLS, LIPIDS THAT
WERE AVAILABLE EXPERIMENTALLY
AND WHICH WE COULD WORK WITH
COMPUTATIONALLY, RIGHT?
SO THAT 8 LIPID OR COMPLEX
MEMBRANE ENVIRONMENT THAT WE'RE
USING IN THE SIMULATIONS WE CAN
ALSO RECONSITUTE IN A MEMBRANE
MUMMI -ITICs IN THE LABORATORY
AND DOING THE EXPERIMENTS IN THE
LABORATORY WITH CELLS WHERE WE
CAN LABEL LIPIDS OR CHEMICALLY
WITH THE DEFINED SYSTEM TO
VALIDATE A LOT OF OUTPUT.
IT'S CORRECT.
THE ULTIMATE VALIDATION THAT THE
SIMULATIONS ARE CORRECT OR YOU
KNOW INFORMATION THAT CAN BE
USED TO FEEDBACK INTO THE
SIMULATIONS WILL COME FROM
EXPERIMENTAL APPROACHES.
>> IT WOULD BE VERY HELPFUL AS
WE'RE MOVING TOWARD LIPID
TRANSVEKSS FOR OTHER THINGS.
ADDITIONAL INSIGHT YOU GAIN
COULD BE FUNDAMENTALLY CHANGED
TO THE DYNAMIC THINKING IN THE
FUTURE.
THANK YOU.
>> JOHN, I BELIEVE YOU'RE NEXT.
>> I'M CURIOUS, YOU DIDN'T SHOW
US ANY DATA TO SHOW AGREEMENT
BETWEEN SINGLE MOLECULE FRET AND
WHAT THE SIMULATIONS ARE
PROVIDING.
HOW IS THAT BEING DONE AND IS
THAT DATA BEING USED TO HELP
REFINE THE MODELS IN SOME
MEANINGFUL WAY?
>> RIGHT NOW, WHAT WE'RE WORKING
ON VERY DILIGENTLY AND WITH A
LOT OF EFFORT IS TO ACTUALLY DO
THE PROTEIN ENGINEERING, TO
PLACE THE RIGHT RESIDUES IN
APPROPRIATE PLACES, SO THAT YOU
CAN HAVE A PROTEIN WHERE YOU CAN
ATTACH THE FRET COMPONENTS, TOO,
BUT NOT KILL THE ACTIVITY OF THE
PROTEIN AND SO, THERE'S--WE HAVE
A VERY STRONG PROTEIN
ENGINEERING TEAM HERE THAT IS
WORKING ON THAT AND WE ARE
LABELING THINGS AND STARTING TO
DO SOME OF THOSE INITIAL
MEASUREMENTS.
ANY OTHER QUESTIONS.
PERHAPS TIME WE MOVE ON.
THANK YOU VERY MUCH.
GREAT PRESENTATIONS GUYS.
APPRECIATE IT.
OUR NEXT PRESENTATION IS BY
DR. STEPHEN AND LEO, INNOVATIVE
METHODOLOGIES AND NEW DATA FOR
PREDICTIVE ONCOLOGY MODEL
EVAGZUATION.
>> CAN YOU HEAR ME?
>> YES.
>> I AM DR. STEVENS AND WE WILL
HAVE CONTRIBUTIONS BY RYAN WEIL,
AND JEFF'S ON, WE WILL TALK
ABOUT IMPROVE, THIS IS A NEW
PROJECT IN THE TRIO YOU'RE
LOOKING AT.
IT'S ABOUT TAKING A LOOK AT HOW
WE ANALYZE AND IMPROVE
PREDICTIVE MODELS FOR TUMOR DRUG
RESPONSE, SO NEXT SLIDE.
SO AS YOU KNOW, THERE'S HUGE
POTENTIAL FOR AI TO IMPACT THE
BIOMEDICAL COMMUNITY AND IN
PARTICULAR, WHAT WE'VE BEEN
FOCUSING ON IN THIS PROJECT IS
THE USE OF AI IN PREDICTING THE
OUTCOME OF CANCER THERAPIES,
PARTICULARLY CHEMO THERAPY TYPE
TREATMENTS AND WE THINK THIS
COULD HAVE A HUGE IMPACT, YET,
THE STATE-OF-THE-ART FOR USING
AI, EITHER IN A RESEARCH SETTING
OR EVEN IN A CLINICAL SETTING IS
STILL VERY MUCH AN EARLY DAYS,
IT'S NOVEL AND CHALLENGING TO
UNDERSTAND HOW WELL IT WORKS,
AND WE DECIDED A FEW YEARS AGO
THAT WE NEEDED A SYSTEMATIC
PROJECT TO ASSESS THE
TRUSTWORTHINESS AND
REPRODUCIBILITY OF AI BEING USED
IN THIS APPLICATION AND WHAT WE
MEAN BY REPRODUCIBILITY HERE IS
INTERESTING.
IN THE LAST 4 YEARS, THERE'S
BEEN CLOSE TO A HUNDRED PAPERS
PUBLISHED ON TUMOR DRUG RESPONSE
PREDICTION USING DEEP LEARNING.
AND MOST OF THESE PAPERS CLAIM
TO HAVE SOME NEW NOVEL
CONTRIBUTION TO START OF THE ART
AND WE APPROACHED THIS CHALLENGE
FROM THE STANDPOINT OF COULD WE
BUILD AN ENVIRONMENT THAT WOULD
ALLOW US TO ANALYZE MODELS BEING
PRODUCED BY THE COMMUNITY AND
SAY SOMETHING DEFINITIVE ABOUT
THEIR REPRODUCIBILITY, AND SO
OSO THAT'S THE HIGH LEVEL GOAL.
BY COMBINING NCI AND DOE
TOGETHER, WE'RE BRINGING UNIQUE
CAPABILITIES TLGT LIKE IN THE
PREVIOUS PRESENTATION, WE HAVE
LARGE SCALE COMPUTERS, ON THE
DOE SIDE, WE HAVE LARGE TEAMS
WORKING ON MACHINE LEARNING AND
AI METHODS AND ON THE FREDERICK
SIDE, ON THE NCI SIDE, WE HAVE
TEAMS VERY FAMILIAR WITH CANCER
EXPERIMENTAL CANCER DATA AND
TREATMENT STRATEGIES AND SO ON.
SO WE'RE BRINGING THOSE ASPECTS
TOGETHER AND THE OUTCOME OF THIS
IS A STANDARDIZED FRAMEWORK,
AGAIN, INSPIRED IN SOME WAYS,
SIMILAR TO WHAT FRED AND DWIGHT
WERE TALKING ABOUT, THAT WILL
ALLOW US TO STUDY AND COMPARE
MODELS THAT THE COMMUNITY'S
PRODUCING BUT NOT JUST LIMITED
TO THESE MODELS IN TUMOR DRUG
RESPONSE BUT TO BE USED TO
PREDICT OR ANALYZE THE
TRUSTWORTHINESS AND RELIABILITY
OF OTHER MACHINE LEARNING
MODELS, AND OTHER APPLICATION
AREAS BOTH IN BIOLOGY AND
OUTSIDE OF BIOLOGY.
NEXT SLIDE, PLEASE.
SO THIS IS A PROJECT STARTED IN
FISCAL 22, PHASED IN.
ONE OF THE INTERESTING THINGS
ABOUT IT IS THAT WE HAVE A SET
OF FUNDED COLLABORATORS IN
ADDITION TO THE CORE ACTIVITY AT
ARGON AND AT FREDERICK, AND RYAN
WILL MENTION THAT LATER.
THE PROJECT HAS 2 HIGH LEVEL
AIMS.
ONE IS BUILDING THIS SYSTEM FOR
CURATING MODELS BEING DEVELOPED
BY THE COMMUNITY, AND BEING ABLE
TO COMPARE THEM USING THE POWER
OF SUPER COMPUTERS TO ANALYZE
THEM IN VARIOUS WAYS,
IDENTIFYING ATTRIBUTES THAT MAKE
MODELS PERFORMANCE AND RELIABLE
AND THOSE THINGS THAT ARE LESS
CONTRIBUTING TO THAT.
SO, THINK OF THIS AS A
SEMIAUTOMATIC PROCESS BY WHICH
WE AJUST MODELS AND I WILL GIVE
YOU MORE DETAIL ON THE NEXT
SLIDE AND INCORPORATE THEM INTO
THIS FRAMEWORK AND THEN WE ARE
ABLE TO USE THE SUPER COMPUTERS
TO DO THIS ANALYSIS.
THE SECOND AIM--SORRY, NOT QUITE
READY--BUILDING OUT PROTOCOLS TO
WORK WITH US TO BELL OUT
PROTOCOLS FOR SPECIFYING DRUG
SCREENING EXPERIMENTS WHOSE
OUTCOME WOULD IMPROVE MODELS AND
THEN TO APLOY THOSE PROTOCOLS TO
GENERATE NOW DATA AIMED AT
IMPROVING MODEL PERFORMANCE AND
SOME SOME SENSE USING THE MODELS
THEMSELVES TO TELL US WHAT DATA
WOULD BEST IMPROVE MODELS.
THAT'S AIM 2.
NEXT SLIDE.
SO THIS WILL GIVE YOU A FLAVOR
OF AIM 1.
SO WE TAKE MODELS FROM THE
LITERATURE AND OFTEN WITH THE
HELP AND ENCOURAGEMENT FROM THE
GROUPS THAT BUILD THOSE MODELS.
WE REPRODUCE THEIR BASE LINE
PERPORMANCE IN THE PAPER AND
THEN WE RESTRUCTURE THE CODE IN
A WAY THAT CAN PLUG INTO OUR
ENVIRONMENT, RECONFIRM THE BASE
LINE PERFORMANCE, CONSISTENT
WITH WHAT WAS IN THE ORIGINAL
PUBLISHED MODEL, AND BRING IT
INTO OUR WORK FLOWS WHERE YOU
CAN DO KETAILED ANALYSIS EMPLOY
SO MODEL CURATION IS A TEAM
EFFORT WITH QUITE A FEW PEOPLE
HELPING INSIDE AND OUTSIDE OF
THE FUNDED PROJECT MUCH THE
SECOND THING WE'RE DOING IS
KRIEWR CURATING DATA SO THE
COMMUNITY CORE ACTIVITY OF USING
VARIOUS CANCER STUDIES OVER THE
LAST DECADE OR SO, 1 THING WE'VE
BEEN DOING IS AGGREGATING THAT
DATA AND WE'LL IMIF YOU A NAP
SHOT OF THE SCOPE OF THAT SO
THAT WE CAN ACCOMMODATE ANY
COLLECTION OF DATA THAT USERS
INTEGRATED INTO THEIR MODELS IN
AN AUTOMATED WAY, WE'RE ALSO
MAKING THAT DATA AVAILABLE AS
BENCHMARK DATA TO THE BROADER
COMMUNITY AND THIS MAKE ITS MUCH
EASIER FOR TESTING MODELS IN THE
FUTURE.
SO FINALLY WHAT FRED WAS SAYING,
IT'S A COMPUTATIONAL FRAMEWORK
THAT ALLOWS 1 TO PLUG THEIR
MODELS IN AND ALLOWS THEM TO DO
THE ANALYSIS AND WE WILL GIVE
YOU BRIEF EXAMPLES.
NEXT SLIDE.
SO HERE'S AN EXAMPLE OF ATHAT
WILL SIS, THIS IS 1 TINY EXAMPLE
OUT OF THE HUNDREDS OF EXAMPLES
WE HAVE, SO THIS IS MEASURING
WHAT WE CALL MODEL
GENERALIZATION, SO THE IDEA HERE
IS YOU TRAIN A MODEL ON SOME
DATA AND THIS IS A DRUG RESPONSE
MODEL, TUMOR DRUG RESPONSE MODEL
AND YOU TEST HOW WELL DOES IT
WORK ON DATA IT'S NEVER SEEN
BEFORE, ON TUMOR PROFILES IT'S
NEVER SEEN BEFORE OR ON DRUG
DESCRIBES IT'S NEVER SEEN BEFORE
AND HERE'S AN EXAMPLE OF 3
MODELS.
AND WHAT THESE MATRIXES SHOW YOU
IS THEY'RE ESSENTIALLY ROW
VERSUS COLUMN SO THE ROW IS THE
DATE OF THE MODEL WAS TRAINED ON
AND THE COLUMN WAS THE DATA THE
MODEL IS TESTED ON AND OF COURSE
THE DIAGONALS WHERE IT'S TESTED
ON THE SAME STUDIES DATA OF
COURSE WITH DIFFERENT PARTITIONS
SO IT DOESN'T--IT'S NOT TRAINED
ON THE SAME DATA THAT'S TESTED
ON AND YOU CAN SEE, JUST BY THE
COLOR COATING THAT THE ABILITY
FOR AN AVERAGE MODEL TO BE
TRAINED ON 1 DATA SET AND TESTED
ON ANOTHER DATA SET IS QUITE
CHALLENGING THE GREEN IS THE
POSITIVE, AND THE RED IS THE
NEGATIVE R-QUARED AND THE YELLOW
IS R-QUARED AND YOU WOULD LIKE
TO HAVE A GREEN MATRIX AND THIS
SHOWS THESE MODEL VS DIFFERENT
RESPONSE MADERNS AND THE 1S ON
THE LOWER RIGHT, SHOWS THE BEST
GENERATEDDALLITY OF THESE 3
MODELS AND THESE ARE SIMILAR
MODELS TRAINED ON THE SAME DATA
SHOWING DIFFERENT
GENERALIZABILITY, AND WE'RE
TRYING TO UNDERSTAND THAT,
UNDERSTANDING WHAT ASPECT OF THE
MODEL THAT'S CONTRIBUTING TO THE
VARIABILITY IN GENERALIZATION,
IT'S THE KEY INSIGHT.
ONE THING WE HAVE LEARNED FROM
DOING THIS, ACROSS MANY STUDY
SYSTEM THAT MODELS OFTEN THAT
SHOW VERY GOOD IN-STUDY
GENERALIZATION ARE NOT THE BEST
MODELS FOR OUT OF STUDY
GENERALIZATION, AND THIS IS A
VERY INTERESTING RESULT, IT
MEANS THAT GROUPS THAT ARE
EVALUATING OR PRODUCING A NEW
MODEL REALLY NEED TO TRAIN THEIR
MODEL AND TEST IT ON VERY
DIFFERENT DATA SETS.
ONE OF THE THINGS THIS IS
LEADING US TO IS HOW WE WILL DO
THIS FOR PATIENT-DERIVED DATA,
PATIENT DERIVED ORGANOIDS OR
PATIENT DERIVED XENOGRAPHS, AND
RIGHT HERE, IN THE RIGHT, IS A
PICTURE OF THE MODEL RUNNING ALL
OF THIS.
TO DO THIS YOU HAVE TO HAVE SERL
SUPER COMPUTERS.
NNEXT SLIDE, THIS IS HYPER
PARAMETER OPTIMIZATION, YOU
COULD THINK OF THIS AS AN ONION,
THIS IS TRAIN THROUGH TRAINING
AND AJUST HOW THE MODEL RESPONDS
AND THEN YOU SET UP PARAMETERS
ON THE OUTSIDE CALLED HYPER
PARAMETERS THAT ARE THE
STRUCTURE OF THE MODEL, SETTINGS
OF LEARNING RATES AND THINGS
LIKE THAT AND IT'S VERY COMMON
TO DO A SWEEP OVER THE OUTSIDE
SETTINGS, THE OUTSIDE KNOBS TO
SEE WHICH KNOB SETTINGS PRODUCE
THE BEST MODEL, SO WE'VE BEEN
DOING THAT FOR MANY YEARS, USING
THE SUPER COMPUTER WE CAN RUN
THOUSANDS OF CASES TO GET THE
EXTERNAL MOBS JUST RIGHT, SO WE
DISCOVERED THE PARTITION BY
GENDER, THE MOST SETTINGS OF
THOSE NOBS WERE QUITE DIFFERENT
BYIENDER AND THIS IS NOTED
COMPLETELY SURPRISING BECAUSE WE
CAN PREDICT GENDER FROM THINGS
LIKE RNA-SEQ DATA AND WE KNOW
THAT GENDER INFLUENS LEVELS AND
SO ON, BUT WHAT'S INTERESTING
HERE IS THAT MOST ACADEMIC
GROUPS ARE NOT DOING HYPER
PARAMETER OPTIMIZATION, WHICH
MEANS THAT IT'S NOT OPTIMAL FOR
BOTH GENDERS AND THIS IS A VERY
IMPORTANT RESULT, IT MAY MEAN
THAT IN THE FUTURE 1 WILL WANT
TO BUILD MODELS THAT ARE TUNED
SPECIFICALLY BY GENDER TO HAVE
THE OPTIMUM RESULTS FOR THAT
GENDER, IT'S TOO EARLY TO SAY
IT'S A POLICY WE SHOULD HAVE BUT
IT'S AN INTERESTING RESULT
IDENTIFYING THIS UNINTENDED
GENDER BIAS AND GENDER MODELS.
NEXT SLIDE.
SO AS I MENINGED THE AGGREGATION
OF DATA, THIS IS OUR DATA
PACKAGE WE'VE BEEN BUILDING OVER
THE LAST COUPLE OF YEARS CALLED
[INDISCERNIBLE] DATA.
YOU CAN SEE IT'S AGGREGATION OF
ALL THE TYPES OF DATA THAT THE
COMMUNITIES IS USING TO BUILD
TUMOR DRUG RESPONSES AND WE'VE
BEEN AGGREGATING AND CLEANING
THIS DATA NORMALIZING THIS DATA
AND PUTTING IT INTO A FORM THAT
DEVELOPERS CAN USE WITH A SIMPLE
INTERFACE THIS, IS MAKING
COMMUNITY DATA MORE AI READY AND
WE NEED IT FOR THE MORE INTERNAL
WORKINGS OF THE PROJECT BUT IT'S
A BENEFIT TO THE COMMUNITY TO
HAVE IT BETTER AND WE ORGANIZED
COMMUNITY PARTICIPANTS TO HELP
US CURATE THIS DATA AND THIS
DATA IS MADE AVAILABLE, IT WILL
BE LAUNCHED AT THE AACR IN THE
NEXT MONTH OR SO.
NEXT SLIDE.
RYAN DO YOU WANT TO TAKE THIS 1?
>> YEAH, THANKS RICK.
AS WAS DISCUSSED NOW THAT WE
HAVE VERSIONS READY FOR USE, WE
ARE BEGENERATEDDING TO GROW THAT
ECOSYSTEM QUITE RAPIDLY WITH IN
KIND COLLABORATIONS.
WE HAVE 15 GROUPS ACTIVELY
COLLABORATING IN AN ADDITIONAL
16 GROUPS THAT HAVE EXPRESSED
INTEREST IN SOME FORM OF
COLLABORATION.
WE ARE TRYING TO GROW FAIRLY
SUSTAINABLILY THOUGH SO AS PART
OF THAT WE'RE PRIORITIZING
STRATEGIC COLLABORATIONS SUCH AS
THE 1S BELOW.
COLLABORATIONS WITH NCI PROGRAMS
THAT ARE ALLOWING US TO AMPLIFY
INVESTMENTS AND REDUCE DUPLICATE
WORK.
OUR COLLABORATION IN HCMI, NOT
ONLY PROVIDES US WITH ACCESS TO
THE MULTIOMIC PROFILE ORGANOIDS
AND LINK LONGITUDINAL CLINICAL
DATA BUT IT'S ALSO INTRODUCED US
TO A NUMBER OF RESEARCHERS THAT
HAVE SUBSTANTIAL COLLECTIONS OF
RELEVANT DATA LIKE THE BROOD
CENTER AND DANA-FARBER, THESE
RELATIONSHIPS ARE BI-DIRECTIONAL
THOUGH.
THE RESPONSE DATA THAT IMPROVE
IS GENERATING AGAINST THE HCMI
SAMPLES AND INCREASING THE
VOLUME OF THE HCMI PROGRAM TO
THE COMMUNITY AT LARGE AND
SPECIFICALLY TO THE
COLLABORATORS WHO ARE HELPING
DRIVE THEIR SCIENCE AND THEIR
THOUGHT ABOUT AI AS THEY'RE
BEGINNING TO BRING THEIR AI INTO
SOME OF THESE BIGGER PROGRAMS
FOR EXAMPLE, WE'RE CURRENTLY IN
DISCUSSION WITH THE BROAD TO
HAVE THE MAP PORTAL IMPROVED BY
AI AND FOLLOW THE STANDARDS FROM
IMPROVE FOR THOSE AIs AS THEY
ADD IT TO THE MOUNT.
THE PSRC, THOSE RELATIONSHIPS
WHICH INCLUDE LANS FROM MD
ABDOMENNERSON, UCSD AND
DANA-FARBER.
THEY'RE BI-DIRECTIONAL.
THE IMPROVED DATA BEING
GENERATED AND THE AI BEING
EVALUATED IS ACTUALLY DRIVING
EXPERIMENTS OR WILL DRIVE
EXPERIMENTS FOR THOSE
RESEARCHERS AND THEN THEY WILL
FEED BA DATA BACK TO US AT
IMPROVE, SO THAT WE CAN GAIN A
BETTER UNDERSTANDING OF
RESISTANCE AND OF EMERGING
RESISTANCE AND THOSE OF THE
TUMOR.
AND SIMILARLY THIS IS OUR
FOUNDATION FOR THE ART NET THIS,
INCLUDING UCSD, MARTH LAB AND UO
U AND SLC, AND WE WILL TALK
ABOUT THE CANCERS WE'RE FOCUSED
ON IN A MOMENT BUT WHILE IT'S
BRANCHING US OUT, IT'S KEEPING
BOTH PROGRAMS VERY FOCUSED.
BEYOND JUST THE DATA
COLLABORATIONS AS RICK TALKED
ABOUT, WE ARE FUNDAMENTALLY
LOOKING AT ARK I MODELS SO WE'RE
BRINGING IN THAT COMMUNITY, THE
IDAKER LAB, THE MARTHLAB, THE
UNIVERSITY OF SALT LAKE AND THE
TROY LAB AT U-PITT.
THEY ARE DEVELOPING NOW AI
MODELS FOR TUMOR DRUG RESPONSE
AND SO BY BRINGING THEM INTO THE
IMPROVED FRAMEWORK, HAVING THEM
ADOPT THE IMPROVED FRAMEWORK,
AND HAVE THEIR MODELS BECOME
PART OF OUR ECOSYSTEM, IT'S
REALLY TYING US BACK TO OUR AIM
OF UNDERSTANDING AND IMPROVING
FUTURE MODELS AS AWE COMMUNITY
AND NOT JUST IMPROVE HAVING TO
BE THE 1 OUT THERE DOING IT ALL.
NEXT SLIDE, PLEASE.
ONE BACK.
THANK YOU.
AS RICK MENTIONED IN THE
INTRODUCTION, THE SECOND AIM OF
IMPROVE IS ACTUALLY VERY NOVEL
FOR AN AI EVALUATION PROJECT
SUCH AS THIS BECAUSE WE'RE
GENERATING NEW DATA SETS TO HELP
US EVALUATE THE CURRENT MODELS
AND IMPROVE FUTURE MODELS AND AS
RICK ALLUDED TO, WE'RE USING THE
GAPS AND BIASES THAT WE SEE IN
THOSE MODELS AND THE AI
PREDICTIVE POWER, TO GUIDE THAT
EXPERIMENTAL DESIGN, AND THEN ON
TOP OF THAT, WE'RE TRYING TO DO
IT IN A WAY THAT'S BRINGING US
CLOSER TO PATIENTS, SO MOVING
AWAY FROM IMMORTALIZED CELL
LINES TO PDOs.
OUR COLLABORATION WITH THE HCMI
IS ONLY 1 PART OF THIS AND THEIR
COLLECTION IS VERY IMPORTANT
BECAUSE IT GIVES US THOSE
MULTIOMICLY PROFILED ORGANOIDS
SO WE CAN COST EFFECTIVELY DO
OUR RESPONSE DATA ANALYSIS AT
SCALE BUT WE'RE ALSO LOOKING AT
THE FUTURE.
AND AS PART OF THIS, WE'RE
GATHERING RESPONSE DATA FOR
THINGS LIKE ADVANCED IMAGING
MODALITIES, WE'RE NOT JUST GOING
TO LOOK AT ARE THE CELLS ALIVE
OR DEAD, AND WHILE NO CURRENT
MODELS USE THESE IMAGING
MODALITIES BY GATHERING THEM, WE
CAN PUT THAT DATA OUT THERE, AS
OUR DATA BEING MADE PUBLIC, AND
FUTURE MODELS CAN USE IT,
BECAUSE UNDERSTANDING, YOU KNOW
HOW HEALTHY WERE THE CELLS AT
THE END OF THE THERAPY, OR THE
TREATMENT, THAT'S INTERESTING
AND CAN DRIVE THINGS LIKE THE
SELECTION OF COMBINATION
THERAPIES, AND PENDING WHO YOU
BELIEVE, SOME SAY THESE IMCANCER
CENTERRINGLY MODALITIES CAN EVEN
SUBSTITUTE FOR MORE EXPENSIVE OR
SENSITIVE OMICS ANALYSIS, LIKE
EXPRESSION ANALYSIS.
IT IS FEARED THAT AMPLIFYING
EFFORTS AND READINESS OF DATA
WERE COLLABORATING WITH A NUMBER
OF LABS AND MD ANDERSON, YOU CSD
AS WELL AS CHICAGO, THAT HAVE
COLLECTIONS OF EITHER LARGE OR
UNIQUE CANCER DATA AND BY
WORKING WITH THEM AND DOING
CROSS VALIDATION STUDIES WITH
THEM, WE'RE ACTUALLY ABLE TO
CREATE LENGTHS BETWEEN THEIR
DATA, OUR DATA AND EXISTING DATA
SETS SO THAT WE CAN COMPARE,
CROSS THEM AND USE THEM.
RIGHT NOW WE'RE DOING INITIAL
PILOTS THAT ARE FOCUSED ON
COLORECTAL CANCER BECAUSE IT'S A
HIGH INVENTORY CANCER AND OUR
INITIAL STUDIES SHOWED THAT IT'S
EXTREMELY POORLY PREDICTED BY
EXISTING AI MODELS BUT OVER THE
SUMMER, AND EVEN SOONER IF THE
DATA GOES QUICKLY, WE'RE ADDING
ADDITIONAL CANCERS SUCH AS
ADENOMA, AND SARCOMA AS WELL AS
EXPABDING DRUGS FROM THE INITIAL
SET OF DRUGS WE USED.
NEXT SLIDE.
IMPROVE IS AN OPEN COMMUNITY.
IMPROVE WAS CONCEIVED OF FROM
THE BEGINNING TO BE OUTWARD
FACING.
AND THE RESOURCES BEING
GENERATED WERE BEING GENERATED
TO SUPPORT COMMUNITY NEEDS.
WE SAY WE'RE TRYING TO LEFT ALL
THE BOATS.
SO IN ADDITION AS RICK MENTIONED
TO NCI, D. O. E. AND ARGON
FREDERICK NATIONAL LABS WE HAVE
OUR CORE MODELING GROUP WHICH
COMPRISES OF MAY O CLINIC, WANG
LAB, TEXT PARTICULAR TECH
UNIVERSITY, WITH THE PAL LAB AND
PACIFIC NORTHWEST NATIONAL LAB
ARRA TOY AND AS WELL AS PACIFIC
NORTHWEST NATIONAL LABORATORY.
AS CAN YOU SEE, ON THE RIGHT, ON
THE BOTTOM, SORRY CAN'T DO THE
POINTER, THIS IS OUR INITIAL
KICKOFF, THIS IS AT ARGON WHEN
WHEN WE KICKS OFF CCMKB SIN IN
JANUARY OF 23.
AND THEN, ON THE TOP RIGHT WE
HAVE OUR YEAR ENDING JAMBOREE,
THAT WAS AT UCSD WHEN WE MET
WITH THE LAB AND OTHERS THERE TO
DO AN INITIAL ROLL OUT.
WE ADDITIONALLY HEALTH EVENTS AT
THE UNIVERSITY OF UTAH SALT LAKE
AND A VIRTUAL EVENT WITH THE
UNIVERSITY OF PITTSBURGH.
WE HAVE A HACKATHON STARTING
TOMORROW AT ARGON AND THEN OUR
NEXT HACKATHON IS IN BOSTON IN
MAY IN 2024 AND THE THEME FOR
THAT IS AI DATA READINESS.
AND THAT'S BEING HELD IN
CONJUNCTION WITH THE BROAD JUST
TO PREVENT QUESTIONS, THIS EVENT
AND AN IMPROVE EVENT BUT WE'RE
COORDINATING WITH THE AI LAB AND
ARGON LAB AND THEY'RE PROVIDING
THROW A FOOTBALL TO FURNISH
JUDGES.
AND THEN THE NEXT SLIDE AND RICK
WILL FINISH US OUT.
>> LIKE THE PREVIOUS PROJECT
EVERYTHING IS OPEN, WE HAVE A
GITHUB WHERE THE COMMUNITY
SHARES CODE AND TUTORIALS AND
EXAMPLES, TOITORIAL ANDS SO
FORTH, SO THERE'S OUR GITHUB
LINK.
ALL THE DATA AND CURATED MODELS
ARE ALSO BEING HOSTED IN THE
MODAC REPOSITORY THAT YOU HEARD
ABOUT BEFORE AT CANCER .GOV AND
WE HAVE A PROJECT WEBSITE THAT
HAS A DESCRIPTION OF WHAT WE DO
AND HOW PEOPLE CAN GET MORE
ENGAGED AND WITH THAT WE ARE
HAPPY TO ANSWER QUESTIONS.
THANK YOU.
>> OKAY.
QUESTIONS?
CAROL?
>> YEAH, THANK YOU.
SO I WAS INTERESTED IN A BUNCH
OF THINGS, BUT INTERESTING TALK.
BUT THE SEX DATA THAT WAS FOUND
IN THERE, BECAUSE MOST OF THESE
DATA ARE FROM PEOPLE OF EUROPEAN
ANCESTRY, DO YOU THINK THAT
THERE'S GOING TO BE BIAS THERE
AS WELL AS DATA FROM MORE
DIVERSE ETHNIC BACKGROUNDS GETS
GENERATED FOR THESE STUDIES.
>> THE SIMPLE ANSWER IS YES, WE
BELIEVE THAT THERE'S RACIAL BIAS
IN THE DATA AS WELL.
WE'VE ACTUALLY DONE THE SLICES,
WE BUILT A TOOL THAT ARK LOWS US
TO SLICE THE DATA BY GENDER OR
SOME OTHER MEASURE AND RACIAL
BACKGROUND IS ANOTHER 1 THAT
WE'VE CONE THE EXPERIMENTS ON
AND OF IT DOES ALSO SEEM TO HAVE
THE SIMILAR CHALLENGES.
WE'RE NOT QUITE READY TO PUBLISH
ON THAT YET BUT I THINK THE WAY
TO THINK ABOUT THIS IS THAT SOME
OF THIS IS CAUSED BY SAMPLE
IMBALANCE, THERE TENDS TO BE
MORE SAMPLES OF CERTAIN SUBCLASS
ASKS THAT HAS AN EFFECT ON IT
AND BECAUSE AI WANTS TO OPTIMIZE
FOR THE MOST ABUNDANT CLASSES.
SO IF YOU HAVE A MINORITY CLASS
THAT GETS LEFT OUT, SO THERE MAY
BE WAYS TO MITIGATE THIS WITH
ADJUSTMENTS IN THE MODELS WHERE
WE CAN COMPENSATE FOR CLASS
IMBALANCE AND WE CAN DO OTHER
THINGS BUT I THINK IT'S STILL A
BIT EARLY IN UNDERSTANDING THE
IMPLICATIONS OF BOTH WHERE THE
DATA IS NOT BALANCED BUT ALSO
WHAT THE COMPUTATIONAL
TECHNIQUES ARE THAT MIGHT
MITIGATE THAT.
>> THANK YOU.
SO MY OTHER QUESTION IS MORE
SELF-SERVING BECAUSE I'M PART OF
THE NCI'S PEDIATRIC PRECLINICAL
IN VIVO TESTING PROGRAM AND SO
WE HAVE A LOT OF TREATMENT
RESPONSE DATA UPON FOR PDX
MODELS, NOT PDOs BUT PDX SO WE
HAVE THE MODELS, GENOMICS,
TREATMENT RESPONSE DATA.
ARE THOSE THE DATA THAT IF WE
MADE THEM AI READY WOULD BE
USEFUL FOR THIS ENDEAVOR AS
WELL?
>> ABSOLUTELY.
ABSOLUTELY.
WE WOULD LOVE TO HAVE THAT DAT
AND THAT'S THE KIND OF DATA
WE'RE HUNTING FOR BECAUSE WE
WANT TO MOVE CLOSER TO THE
PATIENT WHETHER IT'S PDXs OR
PDOs BUT AWAY FROM TRADITIONAL
CELL LINE.
NIT'S OKAY, YOU ARE HEAR FROM ME
LATER IN THE WEEK.
>> OH YEAH, ABSOLUTELY.
I'VE WRITTEN DOWN THE MAY
HACKATHON AND I WILL LOOK UP
YOUR WEBSITE, THIS WOULD BE
FANTASTIC TO LEVERAGE THESE DATA
FOR SOMETHING LIKE THIS.
NTHANK YOU.
>> ANANT.
>> THANK YOU.
REEL KEEPSAKESLY ENJOYED THE
PRESENTATION.
MY QUESTION FOLLOWS ON THE BACK
OF THE PREVIOUS QUESTION.
YOU SAID SOMETHING REALLY
INTERESTING WITH REGARD TO THE
SAMPLE IMBALANCE RESULTING IN
SOME OF THOSE ISSUES THAT YOU
WERE SEEING WITH REGARD TO
GENDER SPECIFIC DIFFERENCES AND
ALSO POTENTIALLY RACE AND
ETHNICITY SPECIFIC DIFFERENCES.
EXCUSE ME--WHICH BEGS THE
QUESTION ABOUT WHETHER WITH
THESE MORE, BIG KIND OF MODELS
WHETHER THERE'S CONCERN ABOUT
BATCH EFFECTS AND WHETHER YOU
EVALUATED WHETHER TECHNICAL
FACTORS CAN PLAY A ROLE.
AND I GUESS THE BROADER QUESTION
ABOUT WHETHER THERE IS A SENSE
OF LOOKING AT MORE EXPLAINABLE
MODELS BECAUSE 1 OF THE
CHALLENGES WE KNOW WITH DEEP
LEARNING FOCUSED MODELS IS THE
OPACITY.
SO I GUESS THE FOLLOW-ON
QUESTION IS ABOUT TRYING TO LOOK
AT MORE EXPLAINABLE MODELS TO
TRY TO SORT OF GET AWAY FROM
SOME OF THAT REPRODUCIBILITY
OPACITY ISSUE.
NYES, YOU HAVE SEVERAL POINTS IN
THERE.
NSO EXPLAINABILITY IS █SOMETIMES
A CHALLENGE.
YOU KNOW IT WAS VERY COMMONLY
TALKED ABOUT A FEW YEARS AGO BUT
SINCE THEN THERE'S BEEN A LARGE
NUMBER OF TECHNIQUES DEVELOPED
TO HELP INTERPRET WHAT DEEP
NEURAL NETWORKS ARE DOING AND I
WOULD SAY EXPLAINABILITY IS
PROBABLY LESS OF AN ISSUE NOW
THAN IT WAS A FEW YEARS AGO.
WE CAN FOR EXAMPLE, BUILD MODELS
THAT HELP EXPLAIN THE DECISION
MAKING OF THE PRIMARY MODEL.
WE CAN DO THINGS THAT EXPLAIN
THE FUTURES THAT THE MODEL IS
USING AND SO FORTH, SO I THINK
EXPLAINABILITY IS LESS OF A
CONCERN.
WE CAN ALMOST USE THESE MODELS
TO TELL US WHAT FEATURES ARE
MOST IMPORTANT AND SO FORTH.
IN TERMS OF BATCH EFFECTS, THE
DATA AND NORMALIZATION WE DO, WE
HAVE VERY SOPHISTICATED
PROCEDURES FOR NORMALIZING AND
RESAMPLING THE DAILY BASIS THEA
AND SO ON TO TRY TO SMOOTH OUT
BATCH EFFECTS AND AT A IN THE
GOOD PART OF THE SPACE, HAVING
SAID THAT IT'S STILL A CONCERN,
WE CAN OFTEN EASILY DETECT WHICH
LABS DATA CAME FROM, THAT
THERE'S A SIGNAL IMPRINT ON THEM
AND EVEN THE TIME OF YEAR THAT
THE DATA WAS PRODUCED SO THAT'S
ALSO A CHALLENGE.
THERE ARE, AGAIN, 5 YEARS AGO, I
THINK SOME OF THESE WERE MOAF
CHALLENGING PROBLEMS BECAUSE THE
COMMUNITY HADN'T BUILT AS MUCH
TECHNOLOGY FOR DIRECTING CLASS
BALANCE OR BATCH EFFECTS OR
THINGS LIKE THAT.
ONE TECHNIQUE THAT'S VERY
HELPFUL, THESE DAYS IS DATA
AUGMENTATION AND SYNTHETIC DATA
AND AND WE'RE ALSO EXPLORING HOW
THAT CAN BE USED TO MITIGATE
SOME OF THESE EEIVETS.
WE CAN OF COURSE COMPARE THE
DEEP LEARNING MODELS TO MODELS
THAT ARE MORE BASED ON MECHANISM
AND THAT'S BEEN AN ONGOING
PROGRAM FOR MANY YEARS IS TRYING
TO FIND MORE MECHANISTIC MODELS
AND WORK THAT INTO THE
FRAMEWORK, SO ALL THESE ARE
IMPORTANT POINTS THAT YOU RAISE
IN IT AND I AGREE THAT THERE ARE
ALL CHALLENGES BUT WE'RE TRYING
TO MANAGE THEM THE BEST WE CAN.
>> THANK YOU.
I'M JUST GOING TO PUSH BACK A
LITTLE BIT THERE WITH THE
EXPLAINABILITY, I THINK WE STILL
HAVE A WAY TO GO WITH TRUE
EXPLAINABILITY AND I THINK THE
CHAL EVENLG WITH SOME OF THE
APPROACHES THAT EXIST WOULD
SUGGEST EXPLAINABILITY BEYOND
EXPLAINABILITY, PARTICULARLY
WITH THE VISUAL ATTENTION MAPS
AND SO ON.
BUT I UNDERSTAND IT IS
CHALLENGING AND COMMEND YOU FOR
THE WORK YOU'RE DOING.
THANK YOU.
>> THANK YOU.
>> SO WE'RE RUNNING A LITTLE
OVER, SO, MARY DID YOU HAVE
SOMETHING YOU WOULD LIKE TO ASK?
>> I JUST PUT IT IN THE CHAT.
ALL RIGHT, FINE.
THANK YOU AND I THINK WE WILL
MOVE ON EMPLOY THE NEXT
PRESENTATION IS ENTITLED MA
SWRAIIC, ACHIEVING NEAR REALTIME
CANCER SURVEILLANCE WITH
AUTOMATIC RECORD ABSTRACTION.
DRS. HANSON AND SHIS U.
>> SO HEIDI AND I WILL CLOSE OUT
THE PRESENTATION ON THE NCI
COLLABORATION SYSTEM MOSAIC, OR
MODELING OUTCOMES USING
ARTIFICIAL AND SCALABLE
INTELLIGENCE FOR CANCER.
NEXT SLIDE.
SO I WANT TO START WITH A LITTLE
BACKGROUND ON THE SEER CENTRAL
REGISTRIES THAT ARE SUPPORTED BY
THE NCI.
STEER ROUGH ATOM VIEDS THE
FRAMEWORK FOR MOSAIC'S
FRAMEWORK, IT WAS A MISSION TO
SUPPORT RESEARCH.
AND THE REGISTRY IS TO IDENTIFY
DATA, TO MAKE IT THROUGH
APPROPRIATE AUTHENTICATION AND
AUTHORIZATION PROCESSES.
SEER CONSISTS OF 18 REG TREES
AND 85% OF THE INCIDENT CASES
RECEIVED BY THE SEER REG TREES
HAVE ASSOCIATED ELECTRONIC
PATHOLOGY REPORTING WHICH IS
CRITICAL IN ORDER TO ACHIEVE
NEAR REALTIME INSTANCE REPORTING
AS WELL AS WORK WE'RE DOING
UNDER MOSAIC.
A CANCER ABSTRACT IN A REGISTRY
IS CONSOLIDATED FROM A NUMBER OF
HOSPITAL ABSTRACTS AND PATHOLOGY
REPORTS AND DEATH CERTIFICATE
ANDS THIS INFORMATION IS
BECOMING MORE COMPLEX AND
HETEROGENIUS AND INCLUDES NEW
DATA SOURCES SUCH AS FRANCIS
COLLINS PHARMACIES AND CLAIMS
AND GENOMIC TESTING RESULTS AND
AS WELL AS REALTIME DATA FIELDS
BUT THIS LARGELY EMANUEL PROCESS
FOR SCREENING AND ABSTRACTION.
THE LAST THING I WANT TO
HIGHLIGHT, IS THE SIERRA DATA
MANAGEMENT SYSTEM OR SEER IMS,
USED BY THE REG TREE.
SEER DMS UTILIZES LINKAGES AS
WELL AS SIMULTANEOUS PROGRAMS TO
SUPPORT A WORK FLOW FOR THE
REGISTRIES.
NEXT SLIDE.
SO THE KEY COMPONENT TO ENHANCES
SEER INFRASTRUCTURE TO SUPPORT A
BROADER SET OF CANCER RESEARCH
ACTIVITY SYSTEM THE WORK WITH
MOSAIC.
THE ACTIVITIES IN MOSAIC ARE
CENTERED ARK ROUND THE REAL
WORLD INFORMATION PIPELINE TO
EXTRACT FREVERGZ IN AN AUTOMATED
FASHION TO SUPPORT NEAR REALTIME
CANCER INITANCE REPORTING AS
WELL AS INFORMATION THAT WILL
SUPPORT BETTER UNDERSTANDING OF
PATIENT TRAJECTORY AT THE
POPULATION LEVEL.
WITH REGARD TO DIAGNOSIS AND
TREATMENT, BEDDING DNCHS AND
OUTCOMES IN REAL WORLD CANCER
PATIENTS SUCH AS SUBSEQUENT
TREATMENT OR METASTASIS IS
INCREASINGLY DIFFICULT.
WE WILL HIGH LIE THE WORK IN
NEAR REALTIME INSTANCE
RESPORTING THROUGH AUTOMATED
ACTION TRACTION FROM
CHARACTERISTICS FROM PATHOLOGY
REPORTS AND NEAR REALTIME CASE
ATTAINMENT FOR CANCER RELATED
REPORT ANDS BETTER UNDERSTANDING
OF OUTCOMES THROUGH PREDICTION
HETAFT SIS.
NEW MANAGES DEVELOPED REPRESENT
AN TRUANT TO CLOSE CRITICAL
INFORMATION GAPS AND CREATE A
TOOL BOX FOR RAPID PHENOTYPES OF
CANCER DATA TO IMPROVE OUTCOMES.
AND THE TOOL BOX CAN BE EXPANDED
TO INCLUDE OTHER INFORMATION FOR
HEALTH OUTCOMES SUCH AS EXPO
STUDIES OF MULTIPLE ENDOCRINIC
MEASURES WHICH IS NEW WORK THAT
WE ARE ALSO GOING TO HIGHLIGHT.
NEXT SLIDE.
ON SO IN THE INNERI SHALL AREAS,
THAT EXTRACT THE INFORMATION
FROM THE REPORS AS THIS
INFORMATION IS CRITICAL FOR
INDENSE REPORTING.
SO THE REPORT AT THE ACCURACY
THRESHOLD REPRESENTING A TIME
SAVINGS OF 14,000 PERSON HOURS
PER YEAR.
THIS PATHOLOGY EXTRACTION API IS
PART OF THE DEFAULT INSTALLATION
OF CRDMS AND CURRENTLY USED WITH
UP TO 19 REGISTRIES AND
EXPANSION IN THE NEXT FEW YEARS.
THEY ALSO FOUND RESULTS FROM THE
APECULIARS I CAN CREATE
EFFICIENCIES IN WAYS WE DIDN'T
ANTICIPATE.
FOR EXAMPLE, THROUGHOUT THE CASE
AS ASCERTAINMENT FOR RESEARCH
STUDIES AND TRAIN XG STAFF.
NEXT SLIDE.
I THINK HEIDI WILL TAKE IT FROM
HERE.
>> I WILL TALK ABOUT HOW WE'RE
USING AI FECNOLOGYS.
I MOSAIC PARTNERSHIP HAS BEEN
SINNER GESTIC BRINGING HIGH
QUALITY SUBJECT MATTER EXPERT
ANDS HIGH PERFORMANCE COMPUTING
EXPERTS AS WELL AS SOFTWARE
ENGINEERS TO DEVELOP INNOVATIVE
SOLUTIONS FOR NEAR REALTIME
DISEASE, SURVEILLANCE IN THE
CANCER COMMUNITY, OVER THE PAST
2 YEARS WE HAVE BROADEN OUR
FOCUS AIMING TO DEVELOP TOOLS
USED BY THE BROADER ONCOLOGY
COMMUNITY AND WE HAVE BEEN DO
THANKSGIVING BY COUPLING
INNOVATIVE RESEARCH AND THE
DEVELOPMENT OF MODULAR SOFTWARE
DESIGN.
MODULAR DESIGN AND COMPONENTS OR
MODULES ARE DESIGNED TO BE INTER
CHANGEABLE, ACCELERATING THE
DEVELOPMENT AND RESEARCH PROCESS
LEADING TO FASTER BREAK THROUGHS
AND QUICKER IMPLEMENTATION OF
RESEARCH OUTCOMES.
WHAT I'M GOING TO TALK ABOUT
NEXT IS OUR MODULAR SOFTWARE
PACKAGE WHICH IS FRESK CO, WE'VE
BEEN FOCUSING ON TRANSLATIONAL
SCIENCE AND HOW WE CAN BRING
EVERYTHING THAT WE'RE DEVELOPING
TO THE BROADER ONCOLOGY
COMMUNITY, SO I'M GOING TO WALK
YOU THROUGH A FEW EXAMPLES OF
HOW WE WE'VE DONE THAT WITH OUR
CURRENT PRODUCTION ALGORITHMS
WHICH ARE OPERATING IN THE SEER
REGISTRY AND AFTER THAT I WILL
WALK YOU THROUGH THE NEW
SCIENTIFIC DEVELOPMENT THAT
WE'RE INCORPORATING INTO THE
MODULAR SOFTWARE DESIGN.
NEXT SLIDE, PLEASE.
BARI IS OUR TOOL FOR CLINICAL
DATA RADIENESS AND WHEN TAKING
CLINICAL NO NOTES AND GETTING
THEM READY--SORRY, LET ME PAUSE
PER A SECOND.
TAKING AI, TAKING CLINICAL NOTES
AND GETTING IT READY IS A
COMPLICATED TASK.
WE HAVE TO TAKE TEXT INPUT
THAT'S HETEROGENERATED AOUS,
FULL OF ERONS AND GET READY FOR
THE AI ALLEGOR RYTH RHYTHMS
REQUIRING TOKENNIZED INPUT.
SO WE HAVE WORKED WITH BARDI,
USING COMMON DATA PREPROCESSING
OPERATIONS INTO THE MODULAR
COMPONENTS.
BARDI SIMPLIFYS DEVELOPMENT AND
UPKEEP OF COMPLEX DATA PIPELINES
MAKING ITENTIOUS FICIENT TO USE
FOR BOTH UROLOGYST PROJECT AND
OTHERS AS WELL.
THE BRITISH COLUMBIA REGISTRY
HAS UTILIZED THIS PACKAGE FOR
PREPROCESSING ALL THE DATA
MENTORSHIP SKILLS PRIOR TO
FEEDING IT INTO THE DOWN STREAM
ALGORITHMS FOR USE.
SO WHAT THIS PACKAGE CAME BACK
AND A SYSTEMATIC DEVELOPMENT
PIPELINE FOR GETTING DATA TO BE
AI READY.
NEXT SLIDE, PLEASE EMPLOY THE
FRAMEWORK FOR EXPLORING SCALABLE
COMPUTATIONAL ONCOLOGY OR
FRRESCO, IS THE PACKAGE THAT
TAKES THE DAILY BASIS THEA THAT
HAS BEEN FOLKENNIZED AND THEN
CREATES PREDICTION ALGORITHMS
FOR SEVERAL DIFFERENT TASKS
INCLUDING REPORTABILITY, SITE,
SUBSITE, THE END BEHAVIOR, AND I
WILL TALK ABOUT A FEW OTHER
TASKS AS WELL.
OUR PARTNERRINGS AT THE VA WERE
ABLE TO PICK UP OUR FRSK O
PACKAGE AND PRETRAIN A MODEL ON
THEIR DATA WITHIN A COUPLE
MONTHS TIMELINE AND HAVE SCALED
THAT UP TO THE ENTIRE VA
POPULATION.
AND THEY HAVE FOUND THAT BY
DOING THIS, IT ALLOWS THEM TO
HAVE HIGHER ACCURACY AND
PREDICTING REPORTABLE REPORTS,
AND THEN TYPICAL MODELS THAT ARE
AVAILABLE OFF THE SHELF.
I BELIEVE THEY USED A ROBERTA
MODEL TO TEST THIS AGAINST,
THEY'RE ALSO ABLE TO PREDICT
BREAST CANCER OR DIFFERENT SITES
RELIABLY AND HIGHER ACCURACY
THAN OTHER TYPES OF MODELS.
SO THIS IS EVIDENCE THAT THE
ALGORITHMS THAT WE'RE DEVELOPING
ARE NOT ONLY BENEFICIAL TO THE
SEER REGISTRIES BUT CAN BE USED
FOR CANCER SURVEILLANCE ACROSS
THE U.S. AND NEAR REALTIME
IDENTIFICATION OF CANCER
PATIENTS.
NEXT SLIDE, PREEZ.
NOW I'M GOING TO TALK ABOUT THE
SCIENTIFIC DEVELOPMENT THAT
WE'VE BEEN WORKING ON OVER THE
PAST YEAR TO IMPROVE OUR
AUTOCODING ACCURACY.
NEXT SLIDE.
BETSY MENTIONED WE ARE
AUTOCODING 27% OF ALL SEER
RECORDS AND WE HOPE TO INCREASE
THE AUTOCODING RATE BY 50% BY
THE END OF THIS CALENDAR YEAR.
WE ARE DOING THAT BY EXPANDING
OUR CURRENT MODELS IN A COUPLE
DIFFERENT WAYS.
FIRST WE'RE--WE HAVE DEVELOPED
AND RELEASED A PATH BIG BIRD
MODEL THAT WAS CHANGE FRIDAY
SCRATCH USING OUR OWN REPORTS.
THIS IS IMPORTANT BECAUSE OUR
PURPOSE OR THE LANGUAGE AND
PATHOLOGY REPORTS IS DIFFERENT
THAN THE LANGUAGE GENERALLY USED
IN SCIENTIFIC REPORTING AND
THEREFORE HAVING A MODEL TRAINED
SPECIFIC TO THAT TYPE OF
LANGUAGE YIELDS TO BETTER
PREDICTION ACCURACYENTIOUS
SPECIALLY THE HARDEST PROPREDICT
SUCH SUCH AS HISTOLOGY, WE SEE A
4-POINT IMPROVEMENT USING THE
MODEL OVER OUR CURRENT
HIERARCHICAL SELF-ATTENTION
MODEL THAT WE HAVE IN PRODUCTION
AT THE SEER REGISTRIES.
WE ARE ALSO DEVELOPING A LEVEL
ATTENTION MODEL WHICH FOCUSES ON
THE PHRASES RATHER THAN JUST THE
SPECIFIC WORDS WHICH IS
IMPORTANT IN ONCOLOGY
PREDICTIONS.
AND WE SEE A BIG IMPROVEMENT
BETWEEN OUR CURRENT
IMPLEMENTATION OF THE HISSAN
LEVEL AND THE ALSO THE ACCURACY
IN THE OTHER MODELS.
IN ADDITION, WE ARE DEVELOPING
NEW MODELS THAT INCLUDE MIXTURE
OF EXPERT WHICH IS ALLOWS US TO
DEVELOP MULTIPLE DIFFERENT TYPES
OF MODELS TO IMPROVE THE
PREDICTIONS, HIERARCHICAL MODELS
AND HETEROGENIUS ENSEMBLING
MODELS.
THE TAKE AWAY FROM THIS SLIDE,
IS THAT WE HAVE SEVERAL DEVELOPS
THAT WILL LEAD US TO BELIEVE WE
WILL GET TO THIS 50% AUTOCODING
RATE IN THE NEAR FUTURE.
NEXT SLIDE.
NSO IDENTIFICATION OF PATHOLOGY
REPORTS RELATE TO CANCER IS THE
OTHER CRITICAL KEY TO ACHIEVING
REALTIME INSTANCE REPORTING
SINCE CANCER REG TREES ARE
AUTHORIZED TO HOLD THE
INFORMATION ON CANCER CASES AND
MOSAIC IS HOPING TO ACHIEVE
THIS, THE QUEPMENT OF
REPORTABILITY API.
CURRENTLY A MIX OF METHODS ARE
USED TO FILTER CANCER RELATED
REPORTS FROM FACILITIES BEFORE
THEY'RE REPORTED AND THESE ARE
LED TO A LARGE NUMBER OF
FALSE-POSITIVES THAT MUST BE
MANUELLY REVIEWED BY THE
REGISTRIES TO CONFIRM A
REPORTABLE CASE.
IMPROVING TO AUTOMATICALLY
SCREEN FOR CANCER RELATED PORTS
IS EXCEPTIONAL FOR OUR GOAL OF
RAPID CASE ASCERTAIN AM AS WELL
AS ACHIEVING REALTIME INCIDENCE
REPORTING.
SO CURRENTLY ON THE PROCESS OF
VALIDATING THE PERFOR THE
PURPOSANCE OF THIS API ACROSS
THE BOUGHTER BROADER SET OF
REGISTRIES BUT HEIDI WILL
PRESENT RESULTS FROM THE
NATIONAL WORK THAT WE'VE DONE
WITH THE SEATTLE REGISTRY.
NEXT SLIDE.
>> AS I MENTIONED BEFORE, PART
OF WHAT WE DEVELOPED IS THIS
ABILITY TO RAPIDLY DEVELOP
MODELS AND THIS IS DONE BECAUSE
OF OUR FRESK O FRAMEWORK.
SO IN THE CASE OF NEAR REALTIME
CANCER CASE IDENT IIVES, WITHIN
A MATTER OF MONTHS WE WILL BE
ABLE TO DEVELOP A MODEL USING
SEATTLE REPORTS, PATHOLOGY
REPORTS FROM OVER 4000 OR SORRY
NEARLY 4 MILLION CANCER
PATHOLOGY RESPORTS AND THIS
ALGORITHM WAS ABLE TO HAVE HIGH
ACRASE MODEL EXPE PREDICTING
IDENTIFYING REPORTABLE OR
NONREPORTABLE REPORTS AND WE
TESTED THIS MODEL FOR BY
ASSISTANCES, BIASES ACROSS
SOCIOLOGICAL DEMOGRAPHIC MODELS
AS WELL AND BECAUSE OF THE
MODULAR DESIGN WE WERE ABLE TO
DO THIS ALL RAPIDLY WITHIN A
COUPLE MONTH PERIOD OF TIME.
WHEN WE'RE THINKING ABOUT NEAR
REALTIME SURVEILLANCE, THIS
RAPID RESPONSE IS HIGHLY
NECESSARY AND SOMETHING WE HAVE
BEEN ABLE DO BECAUSE OF THE
MODELS THAT WE HAVE DESIGNED.
NEXT SLIDE, PLEASE.
IN ARK DITION TO NEAR REALTIME
REPORTABILITY--WHICH MAKE ITS
VERY DIFFICULT TO ASSESS RISK
AND FOLLOW PATIENTS
LONGITUDINALLY.
THE SOLUTION THAT WE HAVE COME
UP WITH IN THE MOSAIC PROJECT IS
TO DEVELOP AN ALGORITHM THAT
CLASSIFIES PATHOLOGY REPORTS FOR
BOTH RECURNESS IN METASTASIS, IN
ORDER TO DO THIS, WE NEEDED HIGH
QUALITY DATA THAT HAD BEENAN
OITATED BY EXPERTS, BECAUSE OF
OUR PARTNERSHIP WITH SEER, WE
WERE ABLE TO COLLECT INFORMATION
ON OVER 67,000 REPORTS ALLOWING
US TO TRAIN HIGHLY ACCURATE
MODEL FOR BOTH RECURRENCE AND
METASTASIS, AND WE ARE CURRENTLY
TESTING THAT MODEL FOR
DEPLOYMENT AT THE SEER
REGISTRIES.
WE CAN SEE HERE THAT FOR
METASTASIS, WE'RE ABLE TO
PREDICT WHETHER OR NOT A REPORT
INDICATES METASTASIS AT .9
ACCURACY LEVEL OF .9.
MAKING IT SOMETHING THAT WOULD
BE VERY USEFUL IN POPULATION
SURVEILLANCE OF RECURRENCE IN
METASTATIC DISEASE.
NEXT SLIDE, PLEASE.
NWE HAVE ALSO BEEN DEVELOPING
REAL WORLD PRIVACY PRESENTED
FEDERATED LEARNING DEVELOPMENTS.
NEXT SLIDE.
SO A HOT TOPIC RIGHT NOW IS
FEDERATED LEARNING, EVERYBODY'S
VERY EXCITED ABOUT IT AND FOR
IMD REASON, IT'S A SOLUTION TO
THE ISSUE WITH DATA STYLING THAT
EXISTS WITHIN HEALTHCARE
RESEARCH.
SILOS MAKE IT NEARLY IMPOSSIBLE
TO DEVELOP MODELS THAT ARE
REPRESENTATIVE OF AN INTIRE
POPULATION AND CAN BE IMPORTED
ACROSS DIFFERENT LOCATIONS,
FEDERATED OFFERS A SOLUTION TO
THAT, HOWEVER, WHAT IS LESS
TALKED ABOUT IN THIS SPACE, ARE
THE BIG SCIENTIFIC CHALLENGES
THAT STILL EXIST WITH CROSS SILO
FEDERATED LEARNING, 1 OF THOSE
BIGGEST CHALLENGES, BEING THE
PRIVACY ACCURACY TRADE-OFF.
BASICALLY, YOU CAN DEVELOP A
MODEL THAT IS HIGHLY ACCURATE,
IN ORDER TO DO THAT, YOU NEED TO
BE MUCH MORE LENIENTOT PRIVACY
SIDE OF THINGS AND SO THOSE
HIGHLY ACCURATE MODELS,
TYPICALLY DON'T HAVE THE LEVEL
OF PRIVACY THAT WE NEED IN
HEALTH SPACE, ALTERNATIVELY, YOU
CAN DEVELOP A MODEL THAT IS
HIGHLY PRIVATE, BUT YOU'RE GOING
TO SACRIFICE ACCURACY BY DOING
SO, BASICALLY BECAUSE WHAT
YOU'RE HAVING TO DO IS INJECT
NOISE INTO THE MODEL, AND YOU
ARE MAKING IT MORE DIFFICULT TO
PREDICT WITH HIGH ACCURACY.
THIS BECOMES EVEN MORE
PROBLEMATIC IN THE HEALTHCARE
SPACE BECAUSE WE HAVE VERY
HETEROGENIUS DATA.
WE UPDATE THAD JUST BY NATURE
VARIOUSYS BETWEEN DIFFERENT
SPACES, IT'S AKIN TO BATCH
EFFECTS IN THE GENETICS WORLD
WHERE WE HAVE A LOT OF
DIFFERENCES WE COULD PICK UP
THAT WOULD BE PURELY FOR THE
FACT THAT DAT APPROVAL FROM SBA
COLLECT INDEED UTAH AS OPPOSE TO
KENTUCKY AND HAVE NOTHING TO DO
WITH THE DIAGNOSE ITSELF.
SO, THESE--WE HAVE BEEN WORKING
ON OVERCOMING OR DEVELOPING NEW
METHODS TO OVERCOME THESE
CHALLENGES, AND I BELIEVE THAT
THERE'S A HUGE POTENTIAL FOR
THOSE MODELS IN THE FUTURE, BUT
THERE'S STILL A LOT OF THINGS TO
DO, THE 1 OPPORTUNITY THAT WE
HAVE IS UTILIZATION OF THE SEER
DATA.
BECAUSE WE CAN TEST WHAT THESE
MODELS DO, IN REAL DATA, WE'RE
ABLE TO COME UP WITH REAL WORLD
SOLUTIONS AND SOMETHING THAT IS
TRULY TRANSLATIONAL.
IN ORDER--IN ADDITION TO THE
WORK WE'VE BEEN CURRENTLY DOING,
WE ARE ALSO HOLING A PRIVACY
PRESERVING HACKATHON THAT WILL
BE HELD IN JUNE OF 2024, THIS
HACKATHON WILL BE FOCUSED ON
IDENTIFYING SPACES WHERE WE
REALLY MAY BE OPEN TO
IDENTIFYING, REIDENTIFYING
INFORMATION AS WE'RE SHARING
GRADIENTS BETWEEN THE MODEL ANDS
THIS IS SOMETHING THAT'S REALLY
EXCITING.
SOMING THAT HASN'T BEEN
QUANTIFIED REALLY WELL, IN THE
NLP COMMUNITY OR IN THE
MULTIMODAL COMMUNITY AND WE'RE
LOOKING FORWARD TO THIS
SCIENTIFIC DISCOVERIES THAT WE
WILL HAVE DURING THAT HACKATHON
IN THE YEARS TO COME.
NEXT SLIDE, PLEASE.
AS BETSY MENTIONED WE ARE
CURRENTLY WORKING ON A PROJECT
WHERE WE ARE LINKING THE
EXTERNAL EXPOETICSOME.
NEXT SLIDE, PLEASE.
WE HAVE THE BENEFIT OF UTILIZIG
THE SEER DATA WHICH GIVES US AN
OPPORTUNITY THAT HAS NOT BEEN
AVAILABLE TO ANYBODY IN THE
CANCER COMMUNITY UP TO DATE.
ESSENTIALLY WHAT WE'RE ABLE TO
DO IS TAKE THE SEER LINKAGES,
THAT HAVE BEEN PERFORMED
BETWEEN SEER INCIDENCE CASES AND
LEXUS NEXUS RESIDENTIAL HISTORY
DATA FOR ALL DIAGNOSIS FROM 2005
FORWARD.
WHAT THAT ALLOWS US TO DO IS FOR
EVERY DIAGNOSE IN THAT SEER REG
STRO THAT HAPPENS AFTER 2005, WE
ARE ABLE TO PULL THEIR
RESIDENTIAL HISTORY FROM 1995 TO
THE PRESENT.
THIS ALLOWS US TO TAKE AN
INDEPTH LOOK INTO EXPOSURES THAT
A PATIENT HAS EXPERIENCED PRIOR
TO THEIR TIME OF DIAGNOSIS, BUT
ALSO DURING THE TIME OF
TREATMENT AND IN THEIR
SURVIVORSHIP YEARS AS WELL.
THIS IS EXTREMELY IMPORTANT IF
WE'RE THINKING ABOUT THINGS LIKE
INDOOR RADON EXPOSURE, WHICH
COULD HAVE A LATENCY PERIOD OF
UP TO 30 YEARS.
UNDER THAT SCENARIO, LINKING
INDOOR RADON EXPOSURE AT TIME OF
DIAGNOSIS JUST ISN'T GOOD ENOUGH
IF WE TRULY WANT TO UNDERSTAND
THE ASSOCIATION BETWEEN RADON
EXPOSURE AND OUTCOME.
AND THIS IS TRUE FOR MANY
DIFFERENT EXPOSURE TYPES
INCLUDING AIR POLLUTION
EXPOSURE, SMOKE, WILDFIRE SMOKE,
WATER DATA, TOXIC RELEASES,
BUILT ENVIRONMENT, SOCIAL
DETERMINANTS OF HEALTH.
SO WHAT WE HAVE BEEN DOING OVER
THE PAST YEAR, AND WILL CONTINUE
TO EXPAND OVER THE NEXT YEAR IS
WE HAVE BEEN COMBINING
INFORMATION ACROSS MANY DEFINITE
SOCIAL AND ENVIRONMENTAL
MEASURES.
WE HAVE BEEN CREATING A DATABASE
THAT SPATIALLY LINKS ALL THIS
INFORMATION AND CAN BE UTILIZED
TO ASSIGN AN EXPOSURE PROFILE TO
A CANCER PATIENT OVER SPACE AND
TIME.
THIS IS A BROADER EFFORT THAT
INCLUDES PARTNERS FROM THE VA,
AND ALSO FUNDING FROM OUR OSCAR
BIOPREPAREDNESS GRANT AS WELL.
NEXT SLIDE, PLEASE.
SO TO BRING ALL THIS BACK TO
TELL YOU WHAT THE SEEMINGLY
THRUST DISLIKE WHEN THEY COME
TOGETHER, I WILL WALK YOU 32
WHAT WE'RE DOING, WHAT WE ARE
TRYING TO DO IS DEVELOP REAL
WORLD AI SOLUTIONS FOR
POPULATION SURVEILLANCE AND
THESE SOLUTIONS WILL ALLOW FOLKS
TO USE IT EITHER IN A SILOED
WORLD OR IN A [INDISCERNIBLE]
WORLD TO BE ABLE TO SPEED UP OUR
TIME FROM DEC OCCURRENCE TO
POPULATION LEVEL DEC STATISTICS
AND THIS IS NOT ONLY IMPORTANT
FOR POPULATION HEALTH
SURVEILLANCE, BUT IT ALSO YIELDS
REAL WORLD SOLUTIONS FOR
PRECISION HEALTH AS WELL BECAUSE
I'M ABLE TO LINK INDIVIDUAL RISK
FACTORS TO INDIVIDUALS AND THEN
LOOK AT HOW THAT AFFECTS
PROGNOSIS, PATIENT'S
TRANSLATIONAL R
ESEARCH--TRAJECTORIES AND
UTILIZE THOSE PORPOPPULATION
HEALTH SURVEILLANCE AS WELL, ALL
OUR SOLUTIONS ARE AVAILABLE,
THEY ARE AVAILABLE FROM GIT-HUB,
REPOE AND THE LINK IS RIGHT
THERE AND WE--AS WE CONTINUE TO
DEVELOP, WE WILL CONTINUE TO
BRING IN OTHER PARTNERS AS WE GO
FORWARD.
BETSY DO HAVE YOU ANYTHING TO
ADD?
>> NO, THANKS.
I THINK WE CAN TAKE QUESTIONS.
NOKAY, QUESTIONS.
GREAT PRESENTATION, THANK YOU
VERY MUCH.
YES, ANANT.
>> FABULOUS PRESENTATION, WHAT
ARE THE PLANS TO TRY TO
INCORNERATE ADDITIONAL KINDS OF
DATA SUCH AS IMAGING OR
ADDITIONAL PATHOLOGY AS PART OF
THE SEER DATABASE?
>> SURE I DON'T KNOW IF ANYONE
WANTS TO ADD ANYTHING BUT SEER
HAS BEEN WORKING OVER THE PAST,
I DON'T KNOW HOW MANY YEARS NOW,
IT'S BEEN TO BRING IN ADDITIONAL
IMAGES THROUGH PARTNERSHIP WITH
OUTSIDE DATA VENDORS SO FOR
EXAMPLE, WE HAVE AGREEMENTS WITH
CVS AND WALGREEN'S TO BRING IN
PHARMACY DATA, WE'VE BEEN
WORKING ON A WHOLE SITE IMAGES
PROJECT TO BRING IN DIGITAL
PATHOLOGY IMAGES WHERE WE HAVE
PARTNERSHIPS TO BRING IN CLAIMS
INFORMATION FOR EXAMPLE, FROM
HEALTHCARE AND UNLIMITED SYSTEM,
SO I THINK, YOU KNOW AS SEER
EXPANDS, THE KIND OF INFORMATION
WE HAVE AND PROVIDES ADDITIONAL
DATA THAT CAN BE USED FOR SOME
OF THE MODELS THAT WE'RE ALSO
DOING WITHIN MOSAIC.
>> YEAH, YEAH, I WOULD JUST LIKE
TO EXPAND, SO OUTSIDE OF JUST
THE DAT SETS FROM SEER, FROM A
MOSAIC PERSPECTIVE, WE REALLY
ARE DESIGNING EVERYTHING SO IT
CAN BE USED JUST OUTSIDE OF THE
SEER DATA.
SO THE FRESK O FRAMEWORK IS USED
AS A FOUNDATION FOR WORK THAT
WE'RE DOING FOR BIOSURVEILLANCE,
AGAIN, BECAUSE THESE MODELS CAN
BE USED ACROSS DIFFERENT
MODALITIES, OR NOT JUST
PATHOLOGY REPORTS ALONE BUT
CLINICAL NOTES, TOO, AND THEN
WE'RE ALSO WITHIN THE RECURRENCE
WORK, WE ARE ALSO DEVELOPING
MULTIMODAL MODELS, SO MODELS
THAT INCLUDE TABULAR
INFORMATION, TEXT INFORMATION,
AND WE HOPE TO EXPAND NOW INTO
OTHER MODALITIES AS WELL.
SO WHAT WE'RE DEVELOPING HERE IS
NOT JUST SPECIFIC TO SEER, BUT
IT'S BECAUSE OF OUR SEER
PARTNERSHIP THAT WE CAN REALLY
DEVELOP TOOLS THAT ARE AVAILABLE
TO THE WIDER ONCOLOGIC
COMMUNITY.
>> THANK YOU.
>> CAROL?
>> YEAH, SO, I THINK IT WAS
HEIDI HA MENTIONED THE
TOKENNIZATION OF CLINICAL NOTES
FOR BARDI.
I'M WONDERING HOW YOU DEAL WITH
VARIATION IN LIKE NOMENCLATURE
SO SOMEBODY CALLING SOMETHING A
FATTY MASS AND ANOTHER 1 CALLING
IT A LIPOMA, DO YOU JUST
TOKENNIZE ALL THE WORDS OR DO
YOU TRY TO DO MAPPINGS OF
EQUIVALENT?
>> DON'T DO RULE BASED MAPPING
AT ALL.
BASICALLY WHAT WE'RE DOING IS WE
HAVE RULES THAT CLEAN THE DATA.
SO WE FOUND THAT THERE ARE
CERTAIN THINGS THAT YOU NEED TO
HAPPEN FOR THE PREPROCESSING,
YOU NEED TO REMOVE ADDRESSES,
IDENTIFIABLE INFORMATION, ALL
THAT HAPPENS, AND THOSE RULES
CAN BE BASICALLY TAILORED TO THE
TASK AT HAND.
SO SOMETIMES FOR BIOMARKERS WE
USE DIFFERENT PREPROCESSING
RULES THAN WE DO ARE IF THE
OTHER TASK, BECAUSE WE WANT TO
MAKE SURE THAT WE'RE KEEPING
CERTAIN INFORMATION.
ONCE WE PREPROCESS THE DATA,
THEN WE TOKENNIZE THE DAILY
BASIS AT, WE DON'T DO ANY RULE
BASED SORTS OF SWITCHES,
MAPPING, ET CETERA.
AND THE TOKENNIZATIONS THAT WE
USE CAN BE DONE EITHER WORD PEEZ
TOKENNIZATION, WE ALSO HAVE
SUBWORK TOKENNIZATION AS WELL
AND WE'RE BUILDING ON OTHER
TOKENNIZATION MODULES THAT ALLOW
US TO CONNECT TO WHAT'S
HAPPENING IN THE BROADER SPACE
IN THE TRANSFORMER AI WORLD.
>> THANK YOU.
>> RODNEY?
>> YOU'RE MUTED.
>> ALL RIGHT.
VERY GLAD TO SEE THE DATABASE
TRANSCRIBING TO SPLG YOU CAN
MODEL WITH THE COLLABORATION
BETWEEN 1 AND THE DIGITAL FOLKS
WITH THAT, SO 1 OF MY QUESTIONS
FOR YOU IS THAT, YOU TALK ABOUT
THIS REALTIME METASTATICS AND
OCCURRENCE ANALYSIS, RIGHT, SO
THIS IS WONDERFUL, SO 1 OF MY
QUESTIONS, IS THAT METASTATICS
PREDICTIONS IS PRETTY IMD,
CORRELATIONS OF 1.9.
HAVE YOU LOOKED AT THE
RECURRENCE PREDICTIONS?
IS THAT AS GOOD OR IS IT STILL
SOMETHING TO WORK ON?
>> WE'RE STILL WORKING ON IT.
WE HAVE LOOKED AT IT.
WE HAVE RECURRENCE PREDICTIONS
AS WELL.
WE'RE USING THE MULTIMODAL
RECURRENCE MODEL SO ESSENTIALLY
WHAT IT DOES IS TAKE INFORMATION
FROM TIME OF DIAGNOSIS, ALL OF
THAT TABULAR INFORMATION,
COMBINES IT WITH A PATHOLOGY
REPORTS THAT ARE COMING AT A
LATER POINT IN TIME AND THEN
WE'RE PREDICTING REOCCURRENCE,
RIGHT NOW FOR NAMODEL, WE'RE
GETTING SLIGHTLY LOWER ACCURACY,
SO SOMEWHERE IN THE .75 RANGE.
WE'VE GONE THROUGH MULTILE
DIFFERENT TESTS IN ORDER TO TRY
TO IMPROVE THAT, AND THERE ARE
OTHER SORTS OF THINGS THAT WE'RE
TESTING CURRENTLY TESTING RIGHT
NOW TO BRING BACK THE ACCURACY
UP.
WE ALSO ARE A BUILT-IN
ABSTENTION WHICH ESSENTIALLY
ALLOWS US TO PREDICT ON THE
THINGS WE'RE VERY CONFIELD
FUNCTIONS KENT IN BUT ABSTAIN ON
THOSE THINGS THAT WE ARE NOT
CONFIDENT IN WHICH IS A NICE
ADDITION BECAUSE, WE CAN'T
PREDICT SOME OF THE RECURRENCE,
OR SOME PATIENTS RECURRENCE WITH
HIGH ACCURACY AND THEN BASICALLY
FOR THOSE THAT WERE NOT QUITE
SURE ABOUT, WE CAN JUST CALL
ABSTAIN, AND HAVE AN INDIVIDUAL
LOOK AT THEM TO GET MORE
INFORMATION.
>> IF I COULD JUST ADD, THIS IS
LYNN, IF I COULD ADD 1 COMMENT
TO THAT, 1 OF THE CHALLENGES
THAT WE HAD IS THAT, YOU KNOW
CURRENT METASTATIC DEC IS AN
EASIER END POINT TO IDENTIFY AND
WHEN WE DEVELOPED OUR GOLD
STANDARD DATA SET, THERE WAS
SOME CONFUSION, EVEN BY THE
EXPERTS WHO WERE CODING THE
RECURRENCE FROM THE--FROM AN
INDIVIDUAL PATH REPORT, SO I
THINK THAT IS RELATED TO THE
LOWER SCORE AS WELL.
>> YEAH, THERE'S QUITE A BIT OF
LABEL NOISE AND THAT'S 1 OF THE
THINGS THAT WE'RE TRYING TO
SOLVE FOR, IS HOW DO WE DEVELOP
A MODEL WHEN THERE'S QUITE A BIT
OF LABEL NOISE IN WHAT'S BEENAN
OITATED.
>> SO WE'VE RUN OVER BUT WE HAVE
TIME FOR LINDA, 1 LAST QUESTION.
OR COMMENT SMRKS SO THIS
QUESTION IS BASED ON, SO THE
SEER COMMUNITIES AND THE DATA
COLLECTED.
SO YOU MENTIONED THAT THE CANCER
REG TREE CAN ONLY RETAIN THE
INFORMATION THAT OUR CANCER
CASES, BUT I'M CURIOUS WHETHER
THERE'S MECHANISM FOR HANDOFF IF
FOR INSTANCE, IT CAME INTO THIS
PIPELINE, THROUGH CANCER
SUSPICION BUT IT LOOKS VERY MUCH
LIKE INFLAMMATORY OR AUTOIMMUNE
DISEASE, IS THERE A MECHANISM TO
HAND IT TO 1 OF THE OTHER SEER
COMMUNITIES FOR THEIR REGISTRY,
AND/OR WHAT HAPPENS WITH
POTENTIAL PREMALIGNANCY DATA?
>> SO CERTAINLY THE REG TREES
CAN OLD ANY INFORMATION ABOUT A
CANCER PATIENT INCLUDING
FOLLOW-UP PATHOLOGY REPORTS, I
DON'T KNOW THERE IS SOMETHING,
IF THERE WAS A REPORT THAT WAS
NOT RELATED TO A CANCER PATIENT
AT ALL.
SO, YOU KNOW PATHOLOGY, YOU KNOW
LABORATORY FACILITIES ARE GOING
TO PROCESS PATHOLOGY REPORTS FOR
NOT JUST CANCER PATIENTS BUT
LOTS OF OTHER DISEASES, WHILE
THE REGISTRY--WHILE THE
FACILITIES MAINTAIN THOSE
REPORTS, I DON'T KNOW IF THERE'S
ANY MECHANISM TO HAND IT OFF TO
ANOTHER LIKE FOR EXAMPLE, CDC,
INFECT YOWZ DEC REGISTRY OR
WHATEVER, ARE YOU AWARE OF
ANYTHING LIKE THAT?
THERE'S CERTAINLY MECHANISMS IN
PLACE FOR CANCER REGISTRIES TO
EXCHANGE INFORMATION WITH EACH
OTHER WHETHER IT'S A SEER
REGISTRY OR A C, DID C REG TREE,
THEY CAN EXCHAIRVELG INFORMATION
ON CANCER PATIENTS.
BUT I'M NOT SURE ABOUT TO OTHER
NONCANCKER REG TREES.
>> THAT'S AN INTERESTING IDEA
BECAUSE WHAT'S HAPPENING RIGHT
NOW IS MANY OF OUR REGISTRIES
ARE ACTUALLY CHANGING THE RULES,
SO THAT THEY CAN RECEIVE
INFORMATION ON NONCANCKER PAST
REPORTS.
SO THEY CAN'T MAINTAIN IT
OVERTIME BUT THEY CAN USE THAT
AS PART OF THEIR SCREENING
PROCESS.
AND YOU KNOW THAT'S A REALLY
INTRIGUING IDEA TO SEE IF THEY
FOUND SOME OTHER DIAGNOSIS THAT
THEY CAN SHARE THAT WITH OTHER
REG TREES, I HADN'T REALLY
THOUGHT ABOUT THAT BUT IT'S A
COOL IDEA AND AN EFFICIENT WAY
TO MOVE THINGS FORWARD.
THANKS.
>> AND THEN I THINK THE OTHER
PART OF YOUR QUESTION WAS AROUND
PRECANCKER INFORMATION, IF
THERE'S ANYTHING HELD THERE AND
CERTAINLY OBVIOUSLY A REG TREE
WILL NONAPOPTOTIC THE
INFORMATION UNTIL A PERSON IS
DIAGNOSED WITH CANCER BUT WITH
THINGS LIKE RESIDENTIAL HISTORY
ONCE THEY'RE A PATIENT IN THE
REG TREE, RESIDENTIAL HISTORY
YOU COULD LISTEN IT TO PREVIOUS
EXPOSURES LIKE EXPOSE ORDER OF
MICRONSIC PROJECT THAT HEIDI
MENTIONED SO YOU COULD LOOK AT
POTENTIAL RISK TBACTORS THAT
THEY HAD BEEN EXPOSED TO EVEN
BEFORE CANCER DIAGNOSIS WITH THE
CONFIRMATION NSOME REGISTRIES TO
CAPTURE INFORMATION ON
PREMALIGNANT LESIONS SO LIKE
CINs 1, 2, 3, I THINK SOME OF
THE PROSTRATE PREMALIGNANT
LESION ANDS THEN OTHER THINGS
THAT SPECIFIC REG STROKINGS
COLLECT, BUT IT'S NOT--IT'S NOT
CONSISTENT ACROSS ALL THE
REGISTRIES.
>> OKAY.
THANK YOU VERY MUCH.
THIS HAS BEEN AN INCREDIBLE DAY
WITH SO MANY OUTSTANDING
PRESENTATIONS SO I THINK SO
MANY, SO MUCH INFORMATION HAS
BEEN PUT FORTH, SO, WE THANK ALL
THE PRESENTERS, IS THERE ANY
OTHER BUSINESS TO COME BEFORE
THE MEETING BEFORE I CALL FOR A
MOTION TO ADJOURN?
OKAY, MAY I HAVE A MOTION TO
ADJOURN?
NSO MOVED N--
>> RODNEY AND SECOND WAS MARY. 4711 02:51:47,096 OKAY, THANK YOU VERY MUCH.