>> TIME TO GO BACK TO WORK. DR. AUSTIN HAS ARRIVED. CHRIS, WE'RE LOOKING TO YOU AS THE FORMER DIRECTOR FOR -- AND ACTUALLY STILL FOR ANOTHER FEW DAYS, THE DIRECTOR OF THE DIVISION OF PRE-CLINICAL INNOVATION SO YOU'LL TAKE US THROUGH THE PROGRAMS THAT ARE IN DPI. >> OKAY. GOOD. SO I WANT TO MAKE IT CLEAR THAT IN THIS PRESENTATION I'M WEARING MY CURRENT HAT AS DIRECTOR OF DPI. I WILL RUN THROW A NUMBER OF PROGRAMS BECAUSE I WANT TO GIVE YOU A SENSE OF THE MENU THIS ORGANIZATION HAS PUT TOGETHER THE LAST DECADE OR SO. BEFORE I DO THAT, I WANT TO USE THIS SLIDE TO ILLUSTRATE WHAT HOLDS THIS ORGANIZATION TOGETHER, AS YOU CAN SEE ON THE LEFT SIDE OF THE SLIDE, THIS ORGANIZATION IS MADE UP OF REAL TECHNOLOGY AFICIONADOS WHERE THE DIVISION IS FULL OF PEOPLE VERY INTO NOVEL TECHNOLOGIES, NOVEL PARADIGMS PAUL AND I WERE TALKING ENGINEERING. WE TRY NEVER TO DO THIS IN A VACUUM BUT IN THE CONTEXT OF WHAT'S ON THE RIGHT SIDE WHICH PATIENTS THAT WE WANT TO APPLY ALL THIS COOL TECHNOLOGY TO. I'M FROM BALTIMORE SO AT THE MOMENT I DON'T WANT TO TALK ABOUT THE YAIN DEE CEES. NONETHELESS HE WAS A -- CAING KEYS. HE WAS A FAMOUS YANKEE, LOU GEHRIG, A PARACYTIC DISEASE WE WORK ON AT THE DIVISION. THIS IS WHAT THE DIVISION LOOKS LIKE AND I WANT TO GIVE YOU THIS ROAD MAP, I'LL KEEP COMING BACK TO IT. OVER AND OVER AGAIN. HOW THIS ORGANIZATION IS VERY DIFFERENT FROM YOUR FATHER'S NIH IF YOU WILL, IN A NUMBER OF WAYS. FIRST IS THAT IT IS A COLLABORATIVE INSTRUMENT. EVERY PROJECT DONE AT THIS ORGANIZATION IS IN COLLABORATION WITH SOMEONE, SOMEWHERE IN THE WORLD. THOSE FOLKS COME TO US EITHER ACT DENIMICS OR FOUNDATIONS OR COMPANIES WITH A PROBLEM IN THE TRANSLATIONAL SPECTRUM THAT THEY'RE STUCK IN. COULD BE ANY STEPS AT THE TOP HERE. THEN THERE ARE ACTIVITIES, DIFFERENT PROGRAMS WITHIN THE ORGANIZATION THAT WE'RE ACTUALLY ALL STARTED INDEPENDENTLY OF EACH OTHER TO SOLVE INDIVIDUAL TRANSLATIONAL ROAD BLOCKS. IMPORTANTLY, EVERY ONE OF THESE PROGRAMS HAS DELIVERABLE T AS THE BOTTOM. I SHOWED YOU A NUMBER OF YEARS AGO PARTIAL TONGUE IN CHEEK, I HAVE SEEN PRESENTATIONS FROM NIH, I NEVER SEEN THE WORD DELIVERABLES ON A SLIDE FROM NIH.w7R WE WERE VERY SERIOUS ABOUT PRODUCING DELIVERABLES USEFUL NOT ONLY TO THE ORIGINAL PROJECT BUT THE COMMUNITY AT LARGE. THIS COULD BE ANYTHING FROM DATA, MOLECULAR TOOL SMALL MOLECULE, DRUG IN IN VITRO PROFILES, ET CETERA. BUT WHAT UNDERLIES THIS IS A A FIRM BELIEF BASED ON THE CLEAR DATA THAT NONE OF THESE PROCESSES EATER INDIVIDUALLY OR TOGETHER WORK VERY WELL. NECESSARY NUMBERS, HOW LONG IT TAKES TO GET FROM HERE TO HERE, THE FAILURE RATE AND COST AND ALL THAT. UNDERLYING THIS IS PARADIGM TECHNOLOGY DEVELOPMENT TO DO WHAT'S DOWN HERE MORE EFFICIENT, BETTER FASTER CHEAPER TRANSLATIONAL THERAPEUTIC DEVELOP. SO I'LL -- DEVELOPMENT. SO I'LL RUN THROUGH A FEW OF THESE BUT CULTURAL ISSUES FIRST AND OPERATIONAL ISSUES SO IT'S DIFFERENT FROM WHAT YOU'RE USED TO IN BOTH THE SCIENCE AND IN THE OPERATION IT DOES SO ALL BPI AT THIS POINT IS INTRAMURAL WHICH MEANS ALL THESE FOLKS WORK WITHIN THE NIH LABS AND THEY ARE EMPLOYEES OF NIH. WE DID THAT FOR NUMBER OF REASONS BUT AS TOM SAID THERE'S NO INDEPENDENT PIs OR LABS, THIS NO TENURE SYSTEM, NOBODY IS ON TENURE TRACK THEY'RE ALL PROFESSIONAL STAFF. EVERY PROJECT IS A COLLABORATION AND ALL THE PROJECTS SOMEWHERE ELSE, 90% ARE OUTSIDE THE NIH. MAINLY SUPPORTED BY EXTRAMURAL INVESTIGATORS AND FOUNDATIONS AND COMPANIES. THIS IS A REALLY WEIRD INTRAMURAL LAB VIA EXTHE TERM REVIEW, NO INTRAMURAL LAB ANYWHERE WHERE THIS IS TRUE. THE SCIENCE IS DIFFERENT, INTERMEDIARY ON PURPOSE BETWEEN THE BASIC MECHANISTIC RESEARCH THAT I STARTED WITH IN MY CAREER. MANY DID AND COMMERCIALIZATION OR CLINICAL APPLICATION. SO IT'S DESIGNED SPECIFICALLY TO HAVE AN ADAPTER FUNCTION. SO WE HAVE ONE FACE WHICH IS TOWARD THE ACADEMIC WORLD AND OTHER FACE TOWARD THE COMMERCIAL WORLD. EVERY PROJECT IS A DUAL USE PROJECT. IT'S A PROJECT THAT HAS A TANGIBLE DELIVERABLE IN TERMS OF TOOL OR DRUG OR DATABASE AND TEACHES US HOW TO DO THIS BETTER. IT TELLS US -- GIVES TECHNOLOGY, COLLABORATIVE PARADIGM, ET CETERA. UNLIKE HOW SCIENCE AND MEDICINE AND NIH FUNDING ORGANIZED IN GENERAL, DPI IS ORGANIZED THIS WAY, IT'S NOT ORGANIZED BY ORGAN SYSTEM. WE'RE BIG DELIVERS IN WHAT OUR MOTHERS TAUGHT US, THE KNEE BONE COLLECTED TO THE LEG BONE CONNECTED TO THE HIPBONE AND MUCH OF SCIENCE AND MEDICINE IS DONE WITH THIS CONCEIT THAT THE HEART IS NOT CONNECTED TO THE BRAIN, NOT CONNECTED TO THE CIRCULATORY SYSTEM, ET CETERA. SO WHEN YOU DO THAT, WE HAVE ALL SEEN THIS, YOU CAN MISS REAL OPPORTUNITIES SO WE ARE DISEASE AGNOSTIC, WORKING ACROSS THE DISEASE SPECTRUM. FOR A NUMBER OF REASONS BUT AMONG IS BECAUSE WHAT WE'RE INTERESTED IN DOING IS DEVELOPING COMMON MECHANISMS AND UNDERSTANDING GENERAL PRINCIPLES TO MAKE THIS PROCESS LESS EMPIRICAL BECAUSE ONE OF THE REASONS THIS IS SUCH A DIFFICULT PROCESS IS YOU THINK ABOUT MOST STEPS IN THIS PROCESS WITH MEDICINAL CHEMISTRY OR TOXICITY, TESTING, WE DON'T UNDERSTAND THE SCIENCE UNDERLIE ANYTHING OF THESE STEPS TO A GREAT GRE. IT'S FAILURE PRONE. WHEN WE FOCUS ON NEW TECHNOLOGIES ENABLING TOOLS DISSEMINATION. I THOUGHT I WOULD SHOW YOU THIS SLIDE, THIS IS A WAY GOOGLE MAPS SHOWS COLLABORATION. SO THE DIVISION HAS OVER 300 COLLABORATIONS WITH INVESTIGATORS ALL OVER THE U.S. AND HOW GOOGLE MAPS 51 COLLABORATIONS IN THE BOSTON AREA AND COLORS ARE THE DIFFERENT PROGRAMS SO YELLOW IS EARLIER, RED AND GREEN LATER STAINL PROGRAMS. FIRST OF ALL THERE'S A VERY BROAD DISTRIBUTION. I WAS GLAD TO SEE WHEN I IS SAW THIS, THIS DOESN'T LOOK LIKE FLY OVER NATION, THERE'S LOTS OF PROGRAMS IN THE MIDWEST HERE. AND THEY'RE REALLY WIDELY DISTRIBUTED. THERE'S ALSO WITH THE INTERNATIONAL MAP WITH EUROPE, CANADA, AUSTRALIA. IF YOU LOOK AT IT FROM THE STANDPOINT OF INSTITUTE DISTRIBUTION THAT IS IF YOU LOOK AT THE AREA WITHIN WHICH DISEASE PREDOMINANTLY FALL, SOMETIMES THIS IS DIFFICULT BUT WE DECIDE WHERE A DISEASE SHOULD GO.q IT IS VERY BROOND FOLLOW IT IS NIH BUDGET AND THE TWO BIGGEST INFECTIOUS DISEASE AL LER PRODUCTS ABOUT A QUARTER. A QUARTER ARE CANCER PROJECTS, 13 WILL BASIC RESEARCH PROJECTS AND NEUROLOGY, AGE, ET CETERA, ET CETERA. THIS IS OPT PROBE DEVELOPMENT PROJECTS, EARLY STAGE. ANOTHER THING THAT'S UNUSUAL IS 80% OF STAFF CAME FROM THE PRIVATE SECTOR. THE REASON FOR THIS, THIS IS WHERE EXPERTISE IS LAYING BUT THE IMPORTANT THING IN ORDER TO GET HIRED TWO THINGS, ONE IS STATE-OF-THE-ART WHERE YOU CAME FROM, FROM THE BEST PLACE PLAIS IN THE WORLD, WHERE YOU CAME FROM. BUT THAT WILL GET YOU IN THE DOOR BUT NOT HIRED. WHAT WILL GET YOU HIRED IS TELLING US HOW TO DO IT BETTER. HOW TO GET IN NOVEL PARTS OF GENOME SPACE, BIOLOGY SPACE, HOW TO DO CHEMISTRY BETTER, HOW TO DO CLIN FARM BETTER, ET CETERA. THE CURRENT STATE-OF-THE-ART IS NOT ACCEPTABLE. LAST THING WE WANT TO DO IS RECREATE THE CURRENT STATE OF ART. BECAUSE THE CURRENT STATE-OF-THE-ART IS NOT GOOD. SO IN ORDER TO GET HIRED YOU HAVE TO TELL US HOW TO DO BETTER. WHEN YOU TAKE AND PUT THEM IN AN ENVIRONMENT DISCONNECTED FROM SHORT TERM COMMERCIAL IMPERATIVE THAT YOU HAVE IN A PLACE LIKE THIS, THEN MAGIC THINGS HAPPEN. PARTICULARLY WHEN YOU ATTACH THEM TO ACADEMIC INVESTIGATOR WHO IS DEEPLY KNOWLEDGEABLE ABOUT THE BIOLOGY THEY WORK IN. THE OTHER THING IS PROJECT TEAMS THIRD STAFF ARE BIOLOGIST, THIRD CHEMIST, ENGINE FOLKS, ET CETERA. SO FAMILIAR THOSE IN BIOTECHS AND IN THIS ENVIRONMENT. ONE REASON WE DID THIS IN THE INTRAMURAL PROGRAM AT THE NIH IN THIS PROGRAM WE DON'T HAVE DEPARTMENTS SO IMAGINE DOING THIS, WE DON'T HAVE TENURE EITHER. BUT WE CAN EMPLOY REALLY EXPERIENCED FOLKS FROM THE PHARMA AND BIOTECH BUT NOT HAVE THEM HAVE THE REQUIREMENT TO PUBLISH NATURE, TRANSLATIONAL SPACE DOESN'T FIT THAT MODEL VERY WELL. SO BUT YOU CAN IMAGINE IF YOU HAD TO DEAL WITH A PROJECT TEAM WHERE YOU HAD ONE IN THE DEPARTMENT OF BIOLOGY, ONE DEPARTMENT OF CHEMISTRY, ONE ENGINEER, ONE COMPUTER SCIENCE AND THEY ALL HAD TO WORK TOGETHER AND HAD CHAIRMEN AND DEAN THEY WERE TRYING TO KEEP HAPPY. HARD TO DO. BUT IT'S EASY TO DO IN THIS ENVIRONMENT. WHAT THIS ENVIRONMENT DOESN'T HAVE IS DEEP BIOLOGY OR DISEASE EXPERTISE. SO HOW IS THE PLACE ORGANIZED? IT'S RUNS ON A MATRIX STRUCTURE, SO WE HAVE THREE BRANCH, THERE'S A DISCOVERY, LEAD DEVELOPMENT AND THERAPEUTIC DEVELOPMENT SIDE, AND THE LOT OF YOU FAMILIAR WITH THIS, THE FUNCTIONS INFORMATICS CHEMISTRY BIOLOGY, ENGINEERING ORTHOGONAL TO THAT. IT OCCURRED TO US FOUR, FIVE YEARS AGO IT WAS ABSURD THAT TEN YEARS AFTER THE GENOME WAS COMPLETED NO PUBLIC SECTOR DATABASE OF RNAi VEENING DATA. AFFECTS INHIBITION OF GENES IN THE GENOME IN A VARIETY OF BIOLOGICAL SYSTEMS SO WITH FUNDING FROM THE INTRAMURAL SDs, SCIENTIFIC DIRECTORS WE STARTED THIS COLLABORATIVE GROUP TO DO RNAi SCREENING PROJECTS. THE PURPOSE OF WHICH NOT ONLY TO DO PROJECTS BUT PUBLISH THE DATA, MAKE THE FIRST PUBLICLY AVAILABLE RNAi SCREENING DATABASE IN ADVANCE OF SCIENCE OF SCREENING BOTH SI RNA, THIS IS A PIE CHART OF COLLABORATION WHICH EXIST IN CNAID AND THE BIGGEST DISEASES FROM THE PROJECTS. WE PUBLISHED A LOT NOT ONLY ON TECHNOLOGIES BUT ALSO -- YOU CAN'T SEE THIS I REALIZE BUT THIS PARTICULAR PROJECT ON PROTEIN DEGRADATION THAT WAS PUBLISHED. AND WE SPENT A LOT OF TIME, THIS PAPER PARTICULARLY IS ALL TECHNOLOGY. HOW DO YOU DO THIS BETTER AND HOW IF YOU WANT TO DO THIS, YOU WANT TO TRY THIS AT HOME, THIS IS HOW YOU HAVE TO DO IT. EXAMPLE MANY THE SMALL MOLECULE SCREENING WORLD, THOSE FROM PHARMA WERE WELL WARE THAT THE CURRENT CONVENTIONAL WAY TO DO SCREENING IS TO DO IT IN A SINGLE CONCENTRATION, SMALL MOLECULE COMPOUND TO AFFECT YOUR TARGET YOU TEND TO TAKE A LARGE NUMBER OF MOLECULES AN TEST IN A SINGLE CONCENTRATION. AND IT WAS KNOWN WE WERE AWARE FOR A LITTLE OVER 500 YEARS THAT THE DOSE OF A DRUG, COMPOUND IS IMPORTANT TO BIOLOGICAL EFFECT. NORMAL SCREENING IGNORES THAT FACT. SO AS YOU MIGHT IMAGINE YOU GET FALSE POSITIVES AND FALSE NEGATIVES SO WHEN WE STARTED THE ORGANIZATION WE THOUGHT THIS IS SILLY, WHY DON'T WE DO PHARMACOLOGY ON EVERY COMPOUND IN THE PRIMARY SCREEN, AND THAT'S WHAT -- HOW WE DO SCREENING AT OUR ORGANIZATION. EVERY COMPOUND IS DONE IN A DOSE RESPONSE FORMAT IN THE PRIMARY SCREEFNLT YOU REALIZE WHAT YOU GET IS PHARMACOLOGY IN EVERY COMPOUND, NOT A HIT LIST OF PUNITIVE POSITIVES. THE IMPORTANT THING FOR US IS THIS GIVES DEEP PHARMACO LORNLGCAL DATA ON COMPOUNDS AGAINST THE TARGET YOU'RE INTERESTED IN, WHICH IS BETTER FROM A SCIENTIFIC PERSPECTIVE, A HUGE HEAD START IN MED CHEM OPTIMIZATION AND A PRACTICAL LEVEL DESCREES IT IS COST BECAUSE YOU CUT OUT SIX MONTHS OF TIME. THAT'S PEOPLE TIME, THREE OR FOUR PEOPLE WORKING FULL TIME ON A PROJECT SO WHAT USED TO TAKE ME LAST PROJECT AT MERCK WAS TEN YEARS AGO NOW, IT TOOK SIX MONTHS FROM THE SCREEN TO HAVING A LIST OF COMPOUNDS WE WERE CONFIDENT OF AND THE WAY WE DO THIS TAKES USrTWO DAYS. HERE SAN EXAMPLE, PAPER PUBLISHING THIS, OF A DIFFERENT TECHNOLOGY TO DRAMATICALLY IMPROVE THE WAY THIS IS CUN. DONE. THIS IS TECHNOLOGY DEVELOPMENT AROUND PREMEDICAL TOXICOLOGY. THIS IS NOVEL TECHNOLOGY IN TWO WAYS. ONE IS THAT IT IS FOCUSED ON THE PROBLEM OF PREDICTIVE TOXICOLOGY, THE OTHER, IT IS A INITIATIVE WHERE FOUR FEDERAL AGENCIES WORK TOGETHER ON A DAILY BASIS AND ACTUALLY DO SOMETHING USEFUL. THIS IS ACTUALLY BEEN ONE OF THE MOST FRUITFUL COLLABORATIONS THAT I HAVE BEEN INVOLVED WITH EPA AND OURSELVES AND COLLEAGUES AT FDA INVOLVED WITH THIS AT THING BEING. AND THIS IS THE PROBLEM. THAT YOU'RE AWARE OF. THAT UNANTICIPATED TOXICITY EITHER PRE-CLINICAL OR CLINICAL POST MARKETING STAGES IS ONE OF THE THREE BIG REASONS WHY DRUGS FAIL SO OBVIOUS TO WORK ON. IN GENERAL FOR TESTING HAS NOT CHANGED APPRECIABLY FOR THE LAST 40, 50 YEARS. THE IDEA TRADITIONALLY IS YOU GIVE ANIMAL OR ENVIRONMENTAL TOXICITY, THEY GET A DOSE, THEN YOU LOOK HERE AT TOXICITY. DO THEY GET WE KNOW LITTLE ABOUT WHAT HAPPENS LITTLE. YOU HAVE LITTLE WAY TO KNOW THE NEXT DRUG GOING TO CAUSE THIS BECAUSE YOU HAVE NO INTERMEDIATE OUTCOME. NO BIOMARKER SO WHAT THIS INITIATIVE IS DOING IS IT'S A VERY AMBITIOUS LONG TERM INITIATIVE, PROBABLY TAKE US TEN YEARS OR SO, METAPHORICALLY WHAT WE'RE DOING IS INSTEAD OF GIVING EACH CHEMICAL AND DRUGS TO A RAT OR PERSON METAPHORICALLY DISSECTING THAT PERSON OR THAT RAT INTO COMPONENT CELL TYPES, LIVER CELLS, BRAIN CELLS, ET CETERA, TWEETING THOSE CELLS, WITH ALL THE CHEMICALS, SEEING THE OUTCOME, LOOKING AT ALL THE CELL TYPES, DIFFERENT PATHWAY WITHIN THE CELLS AND COMPUTATIONALLY PUTTING THE RAT BACK TOGETHER AGAIN AND DEVELOPING PREDICTED MODELS ON BASIS FOR IN VITRO OUTCOMESCH THIS IS ONLY POSSIBLE BECAUSE OF THE ENORMOUS EXPERTISE AT FDA, ON DRUGS AND EPA AND ENVIRONMENTAL CHEMICALS. THIS IS THE INTERPRETABLE DATA YOU GET NOT IMMEDIATELY INTERPRETABLE BUT WHAT YOU CAN DO IS PUT THIS TOGETHER, THIS WAS A MODEL PUBLISHED A COUPLE OF WEEKS AGO WHICH IS PROBLEM WITH HIV AND OTHER DRUGS. LET ME TELL YOU ABOUT SOME PROJECTS THAT HAVE NOT ONLY TECHNOLOGY ASSOCIATED WITH THEM BUT THE DELIVERABLES AT THE BOTTOM. THE FIRST IS LEAD OFF STAGE, THIS IS PART OF THE ORGANIZATION CALLED THE NIH CHEMICAL GENOMICS CENTER STARTED AS PART OF THE ROADMAP LIKE LIBRARIES PROGRAM NOW 8 YEARS AGO. THIS ORGANIZATION AS OF TODAY HAS 240 COLLABORATIONS WITH PEOPLE ALL OVER THE WORLD EVERY POSSIBLE AREA OF BIOLOGY DISEASE IN THE SPACE THIS ORGANIZATION WORKS IN IS ASSAY DEVELOPMENT, SCREENING INFORMATICS, MEDICINAL CHEMISTRY, TARGET THE LEAD IF YOU WANT TO THINK OF IT THAT WAI. THE FOCUS OF THIS ORGANIZATION IN TERMS OF THE DISEASES THAT IT WORKS ON IS ONE MINUS PHARMA. IF YOU TAKE THE UNIVERSE OF DISEASES AN TARGETS AND SUBTRACT WHAT BIOPHARMA WORKS ON, IF YOU DISCOVER 95% OF DISEASES ARE NOT BEING WORKED ON THIS ORGANIZATION DOES NOT WORK ON CONVENTIONAL DISEASES THAT ARE ALREADY BEING WORKED ON. THE OUTCOME ARE USEFUL CHEMICAL PROBES AND LEADS TO UNDERSTAND HOW BIOLOGY WORKS AND ALSO LEADS FOR FURTHER DEVELOPMENT. NA A HUGE EMPHASIS ON NOFL TECHNOLOGIES AND PARADIGMS TO PROVE THE SUCCESS RATE IN THE SPACE. OVER THE LONG TERM MORE VERY BIG BELIEVERS IN THE FACT THAT THE ONLY WAY WE'RE GOING TO MAKE THIS WHOLE PROCESS MORE PREDICTIVE IS IF WE UNDERSTAND THE GENERAL PRINCIPLES WHICH MOLECULES AN TARGETS INTERACT. WE DO HIGH THROUGH PUT SCREENING BECAUSE WE DON'T UNDERSTAND THE PHYSICAL CHEMISTRY HOW THAT WORKS. BUT THAT PROBLEM, IF WE UNDERSTOOD THAT PROBLEM WE WOULD BE GOOD AT PREDICTING EFFICACY AND TOXICITY. THAT'S THE LONG TERM VISION OF THIS ORGANIZATION. LET ME GIVE YOU ONE EXAMP REDUCING THESE TO PRACTICE TO SHOW YOU HOW THIS WORKS. THIS IS A PROJECT THAT TOM MENTIONED BRIEFLY AT INTRODUCTION. DON'T WORRY TOO MUCH ABOUT THE SCIENCE, THOUGH THE SCIENCE IS FANTASTIC, WHAT I WANT YOU TO GET APPRECIATION OF HERE IS MORE THE SOCIOLOGY, HOW THIS WORKS. THIS IS A PROJECT ON DEVELOPING ACTIVATORS OF ENZYME WE LEARNED ABOUT IN BIOCHEMISTRY AND PROMPTLY FORGOT. PYRUVATE KINASE. WE STARTED WORKING ON THIS FOR TECHNOLOGY DEVELOPMENT REASONS, PARADIGM. WE HAD NO IDEA THAT IT WAS INVOLVED IN CANCER OR OTHER DISEASE FOR THAT MATTER BUT WORKING ON IT FOR TWO, THREE YEARS, THIS GUY PUBLISHED A COUPLE OF NATURE PAPERS ON THE FACT THAT DECREASE IN PKM-2 ACTIVITY SEEMED RESPONSIBLE FOR IN PART THE WARBERG EFFECT SO WE CALLED UP LOU AND SAY YOU KNOW ABOUT CANCER BUT NOT ABOUT DRUGS WE KNOW ABOUT DRUGS BUT NOT A LOT ABOUT CANCER. WE NEED A CRYSTALOGRAPHER SO WE CALLED THIS GUY WHO DIDN'T KNOW ABOUT CANCER OR DRUGS BUT KNOW ABOUT STRUCTURES. TOGETHER THIS GROUP DID INCREDIBLE WORK. VERY QUICKLY. I'LL SHOW YOU HOW IT WORKS. IN THE BEGINNING WE NEEDED AN ASSAY SO WE DEVELOPED ONE, DON'T WORRY ABOUT DETAILS BUT THAT REQUIRED A WHOLE LOT OF EXPERTISE AND ASSAY DEVELOPMENT AND ROBOTICS AND SCREENING, SCREENED 300,000 COMPOUNDS AND DOSE RESPONSE THREE SERIES. OPTIMIZATION APPRECIATED BY ACADEMIC COLLEAGUES THAT ALL THIS OPTIMIZATION WAS TO INCREASE SOLUBILITY. THERE IS SOMETHING ABOUT POTENCY QUITE GOOD. WE DID A LARGE AMOUNT OF PHARMACOLOGY SHOWING THAT THESE THINGS DID ACT AS ACTIVATORS, DID STRUCTURAL PIOLOGY WORK WHERE THESE BOUND IN THE PK HOMOTETRAMER. THEN ONCE WE HAD PROOF OF PRINCIPLE IN THIS ARENA, WE GOT A TRUE LEAD DEVELOPMENT DOING THINGS LIKE HALF LIFE AND LIVER MICROSOMES AND THINGS LIKE THAT. AT THIS POINT WE STARTED PUBLISHING PAPERS, THAT CAME OUT THE 26th OF AUGUST, THREE WEEKS AGO, PUBLISHING THESE STRUCTURES, AND JUST TO GIVE YOU A SENSE, THIS IS THE -- THESE COMPOUNDS ACTIVATION ACTIVITY ON THE ENZYME, THIS IS ON PKM-1 SO SHOWS YOU A SPECIFIC DECREASE GROWTH OF TUMORS AND XENOGRAPH MODELS SO THEY DO EXACTLY WHAT YOU EXPECT THEM TO DO. AT THIS POINT WHAT HAPPENED WAS WE GOT CONTACTED BY TWO BIOTECH COMPANIES IF BOSTON. THESE ARE NOW MOVING FORWARD AS COLLABORATIONS WITH THOSE COMPANIES SO I CAN TELL YOU IS 100 OTHER STORIES BUT WHAT I WANT YOU TO TAKE AWAY IS IT ONLY HAPPENED BECAUSE THIS IS A TEAM WHICH RECOGNIZES THAT EACH MEMBER OF THE TEAM PERFORM TOP LEBRON JAMES LEVEL BUT THIS TIME TEAM HAS TO WORK AS A TEAM WITH A SINGLE OUTCOME. THAT OUTCOME CANNOT HAPPEN VIA ONE MEMBER, IT TAKE IT IS TEAM WORKING TOGETHER. WHEN THAT HAPPENS THIS CAN GO VERY QUICKLY. ANOTHER EXAMPLE. I'M GOING TO EMBARRASS TWO COUNCIL MEMBERS AT THIS POINT BECAUSE IT INVOLVED TWO OF THEM. SO WE WERE INTERESTED IN REPURPOSING, AS A NUMBER OF US DID, THIS HAD BEEN DONE IN A FAIRLY SERENDIPITOUS WAY SYSTEMATIZE SERENDIPITY. IF YOU'RE GOING TO DO THAT TOUGH HAVE A LIST APPROVED FOR HUMAN USE WORLDWIDE. WE EXPECT THAT WOULD BE A FAIRLY EASY LIST TO PUT TOGETHER. TURNED OUT FOR A VARIETY OF REASONS IT WAS VERY HARD, IT TOOK FIVE YEARS TO DO. BUT IT'S ALL DONE NOW. THIS IS NOT -- IT'S A STRATEGY, PUT IT OUT THERE AND SHOW EVERYBODY HOW TO USE IT. THIS IS A PAPER WE PUBLISHED ABOUT A YEAR AGO. THIS COLLECTION HAS -- THIS IS OUTDATE BUD EVERY SMALL MOLECULE APPROVED BY FDA, EU IN JAPAN AND 800 INVESTIGATIONAL DRUGS. HUGE PROBLEM LOGISTICALLY. IF YOU'RE INTERESTED IN THE STROIR, STEVEN KING NOVEL, PA THAT'S WHAT THE PAPER DOES BUT TELLS YOU WHY IT'S A HARD PROBLEM BUT IT'S NOW SOLVED. WE PUT THE DATABASE ON THE WEB AND YOU CAN DOWNLOAD ON TO YOUR COMPUTER. I DON'T HAVE SCREEN SHOTS BUT YOU CAN ASK IT TELL ME WHAT'S APPROVED IN THE U.S., WHAT'S IN CANADA, VETERINARY USE, WHAT'S APPROVED ONLY INVESTIGATIONAL USE. USED TO BE ON THE MARKET AND TAKEN OFF THE MARKET. YOU CAN SEARCH DISEASE OR TARGET, WHATEVER YOU WANT. THIS IS IMPORTANT FOR PEOPLE WHO WANT TO PUT THE PHYSICAL COLLECTION TOGETHER. WE TOLD PEOPLE WHERE WE GOT THE PHYSICAL SAMPLES OF A COMPOUND. THAT'S A HIGHLY NON-TRIVIAL PROBLEM. IF YOU WANT TO STUDY THIS IN YOUR ANIMAL MODEL WHERE YOU GET IT SO THAT'S ALL DONE NOW. HERE IS AN EXAMPLE OF WHAT WE APPLY THIS TO. THIS IS A CANCER CALLED CHRONIC LYMPHOSITIC LIEU CHEMOIA. LIKE MOST CANCERS VIRTUALLY ALL CANCERS, BECOME REFRACTORY TO TREATMENTS AVAILABLE AND PATIENTS VIRTUALLY RELAPSE. THIS IS A PROJECT LOOKING AT RELAPSE OR REFRACTORY CLL. WHAT WAS DONE HERE WAS TO DO WHAT WE LIKE TO DO WITH REPURPOSING COLLECTION. NOT FOCUS ON ENGINEERED SYSTEMS BUT USE HUMAN CELLS SO IN THIS CASE SIX PATIENTS WENT TO THE CLINICAL CENTER GOT FOR REECEED, WE CAN GET A BILLION CELLS OUT OF PATIENTS DRIVEN TO OUR CENTER SCREEN ACROSS A DRUG COLLECTION IN A DAY. IN NINE CONCENTRATIONS AND WE COMPARED WITH FIVE NORMAL DONORS WHO GOT FOR REECEED TO THE BLOOD BANK. EACH ON THIS HEAT MAP EACH COLUMN IS A PERSON, IS A PATIENT AND EACH ROWS IS A DRUG. YOU'RE JUST LOOKING THE RED THINGS ARE JUST -- THE DRUGS THAT HAD AN EFFECT IN THESE PATIENTS. ABOUT 2700 DRUGS GOING INTO THE SUB BASE THAT DIDN'T KILL THE CELLS. DID THESE KILL THE CLL CELLS OR NOT, YOU CAN SEE ALL THESE KILLED THE CLL CELLS, THAT'S HOW WE SELECTED THEM. IF YOU LOOK AT THESE FIVE HERE THESE ARE NORMAL DONORS, THESE ARE B CELLS, MOST OF THE CELLS, MOST DRUGS KILLED THE CELLS FROM THE NORMAL DONORS AS WELL EXCEPT A SMALL GROUP DOWN HERE WHERE THE DRUGS -- I CALL THEM DRUGS BECAUSE THEY'RE ON THE MARKET, LITTLE OR NO EFFECT ON NORMAL B CELLS, ONE TURNED OUT TO BE AN OLD RHEUMATOID ARTHRITIS DRUG. THIS IS A GREAT EXAMPLE FOR US OF SOMETHING THAT ONE NEVER WOULD HAVE GUESSED. AT LEAST I NEVER WOULD HAVE GUESSED. WE KNOW WHAT THIS MECHANISM OF ACTION IS, AT LEAST WE THINK WE DO. WE THINK IT WORKS ON THYROID REDUCTASE BUT A GREAT EXAMPLE HOW NOT ONLY CAN YOU MAKE SOMETIMES A RAPID THERAPEUTIC ADVANCE BUT ALSO YOU CAN UNDERSTAND ABOUT THE BIOLOGY, IMPORTANT THING ABOUT THINGS ABOUT BIOLOGY OF DISEASE THROUGH PHARMACOLOGY OF COMPOUNDS WORKING ON DISEASES SO THERE'S A RICH HISTORY PARTICULARFULLY IN PSYCHOPHARMACOLOGY BUT ANOTHER EXAMPLE. IMPORTANT THING AT THIS POINT WAS THAT WE WANTED TO BE ABLE TO GET THIS INTO PATIENTS AS RAPIDLY AS POSSIBLE. TYPICAL WAY WE WOULD HAVE DONE THIS, WE REALLY HAVE TO KEEP THIS INTERNALLY. WE CAN'T PUBLISH IT. WE CAN'T TELL ANYBODY BECAUSE GOT TO GET TENURE. WHAT HAPPENED IN THIS SITUATION IS THE COLLABORATOR OF THE CLINICAL CENTER WHO WE WERE DOING WORK WITH SAID I WOULD LOVE TO WORK TOGETHER WITH YOU ON THIS BUT I HAVE TO GET TENURE. THEREFORE, DESPITE THIS, AND DESPITE THE FACT THAT I WENT INTO MEDICINE TO HELP PATIENTS I CAN'T WORK WITH YOU ON ANY MORE BECAUSE I'M NOT GOING TO GET A CELL PAPER. SO WE SAID GOODBYE. CAN'T WORK WITH YOU. WHICH WAS EXTRAORDINARY TO US BUT I UNDERSTAND IT BECAUSE HE'S PAYING ATTENTION TO INCENTIVES ALL OF US DEAL WITH EVERY DAY. SO I CALLED SCOTT WE'RE WHO I KNEW AT KU WHO KNEW ABOUT REPURPOSING AND HE WAS WORKING WITH LEUKEMIA LYMPHOMA SOCIETY. WE NEED TO GET THE BEST PEOPLE IN THE WORLD ON REPURPOSING AN CLIN FARM AND PEOPLE WHO KNOW MORE ABOUT LEUKEMIA THAN ANYBODY IN THE WORLD, THAT'S THESE TWO FOLKS. WE FORM RAPIDLY, LEARNING COLLABORATIVE TEACH US NOT ONLY HOW TO REPURPOSE BUT HOW TO DO THIS IN A GENERALIZABLE WAY AND WE NOW REPLICATED THIS MODEL SEVERAL TIME, WORKING ON SARCOMA WITH THE SAME MODEL NOW. IN A DIFFERENT NON-PROFIT BUT POINT IS, THIS ORGANIZATION WENT FROM DISCOVERY OF THIS IN THE LAB, IN OUR LAB IN 2009 TO DOSING THE FIRST PATIENT IN TWO YEARS. THE IMPORTANT THING IS IN THE TIME IT TOOK BETWEEN SIGNING THE AGREEMENT WHICH TOOK A YEAR, I HAD TO PUT THIS COLLECTION TOGETHER, IT TOOK US A YEAR FROM SIGNING THE AGREEMENT TO BEING (INAUDIBLE). SO THIS HAPPENS QUICKLY BUT BASED ON RECOGNITION OF THE IMPORTANCE OF THE TEAM. TREND IN BRIDGES, THESE ARE THE SAME OPERATIONAL MODEL BUT DOWN HERE ON THE MORE DISSAL END OF THE SPECTRUM, THESE ARE THE DELIVERABLES DOWN HERE. THE BRIDGES PROGRAM IS KNOWN AS RAID. NIH RAID. WE DECIDED TO CHANGE THE NAME BECAUSE WE THOUGHT WE GOT FEEDBACK THAT THIS WAS A SLOW PROGRAM SO THIS WAS NOT RAPID ACCESS TO INTESH VENGS DEVELOPMENT. WE HAVE TO CALL IT SAID FOR SLOW ACCESS. PLUS WE THOUGHT A DRUG DEVELOPMENT PROGRAM NAMED AFTER INSECTICIDE IS PROBABLY A BAD IDEA SO WE CHANGED IT TO BRINGING INTERVENTIONAL DEVELOPMENT GAPS: THIS IS A CONTRACT ACCESS PROBLEM PROGRAM SO IF AN INVESTIGATOR IN A COMPANY OR ACADEMIC INSTITUTION NEEDS A KILO OF API GROWN UP MADE UP OR JUST NEEDS A SIX MONTH TOX STUDY DONE, WHERE THEY GO? THIS IS WHERE THEY CAN GO. THE PROJECT VERSUS TO ENTER WITH CANDIDATE IDENTIFY NO MED CHEM IS DONE. ANY DISEASE IS ELIGIBLE HERE. SO WE -- THESE PROJECTS WE DO A GAP ANALYSIS, FIGURING WHAT THEY NEED TO GET TO THE STAGE THEY NEED TO GET TO. THEY HAVE TO EXIT AT OR BEFORE IND. THESE ARE NOT GRANTS, IT'S A RESOURCE ACCESS PROGRAM. ANY THERAPEUTIC MODALITY, PEPTIDES, GENE THERAPY ANTIBODY, ET CETERA. ELIGIBLE APPROXIMATE PRIA CAN'TS AS ANYBODY. -- APPLICANTS. SBI,R, NOT LARGE COMPANY, SBIR ELIGIBLE IF YOU'RE A BUSINESS. AND JUST METRICS, BEEN 34 PROJECTS APROVED FOR THE LAST SEVERAL YEARS, 19 APPROVED PROJECTS. 100% SUCCESS RATE GIT GETTING INDs APPROVED FOR WHICH BRIDGES PRODUCED THE DATA. NUMBER OF PROJECTS IN PHASE 1, PHASE 2 AND NUMBER OF AGES LICENSED AS WELL. THIS IS WHAT THE PORTFOLIO LOOKS LIKE. NOT IN ANY DETAIL. THE ONLY THING I WANT TO SHOW YOU FOR TREND AS WELL, IF YOU LOOK AT ORG TYPE HERE, IT'S ABOUT A QUARTER, A THIRD BIOTECH AND THREE QUARTERS ACADEMIC, LOTS OF DIFFERENT KINDS OF THERAPEUTIC MODALITIES. TREMENDOUS DIVERSITY IN DISEASE, METABOLIC DISEASE, EYE DISEASE, RHEUMATOID DISEASE, TREMENDOUS VARIETY. ONE OF THE THINGS THAT HAS COME OF THIS PROGRAM IS TRYING TO FIGURE HOW TO DO THIS BEMPLET HOW DO WE -- BETTER HOW WE DO GAP ANALYSES TO MOVE FORWARD AS RAPIDLY AS POSSIBLE. SO LASTLY, TREND. TREND IS THE MODEL HERE, A LITTLE DIFFERENT FROM BRIDGES, IT'S PROBABLY MORE ORGANIZATIONS THAT AT LEAST EQUAL NUMBER IF NOT MORE ORGANIZATIONS WHERE THE TREND MODEL FIXEDED BETTER. THE TREND MODEL IS FOR FOLK WHOSE DONE KNOW WHAT THEY NEED. THEY HAVE AN IMPORTANT DISCOVERY BUT IT IS A COMPREHENSIVE DRUG DEVELOPMENT COLLABORATION BETWEEN DPI AND EXTRAMURAL LAB THAT HAS DISEASE EXPERTISE. AND THE PROJECTS ARE A LITTLE DIFFERENT, THEY CAN ANY STAGE LEAD UP UNTIL IND IF SOMETHING IS AN IND WE'LL TAKE IT. IT CAN'T BE STEADY DISEASE, DRUG CRITERIA, OR WHO TROPICAL DISEASE LIST THAT'S WHAT NEGLECTED MEANS. IMPORTANTLY THIS IS A PROJECT, THIS IS AN INITIATIVE WHICH TAKES PROJECTS JUST TO THE POINT BEING ABLE TO HAVE EXTERNAL ORGANIZATION, MAKE A BUSINESS CASE TO ADOPT THEM. THAT EXTENT TO TAKE THESE PROJECTS IS IB VERSELY PROPORTION -- INVERSELY PROPORTIONAL TO THE TARGET COME PAWND REGULATORY CLINICAL RISK OF THESE PROJECTS. BUT MAXIMUM 2A LIKE TOM TALKED ABOUT. SO THERAPEUTIC MODALITIES ARE SMALL MOLECULES, WE LOVE TO WORK DEVICES AND GENE THERAPY AND OTHER THINGS BUT WE'RE LIMITED BY THE BUDGET STUCK AT $24 MILLION.X I'M STRUCK BY BELL'S STATEMENT AND OTHERS LIKE CHDI THAT ORGANIZATIONS LIKE (INAUDIBLE) THREER FOUR TIMES THIS AMOUNT OF MONEY ON A SINGLE DISEASE, SO $24 MILLION IS A MODEST AMOUNT OF MONEY IN THIS SPACE. BUT AGAIN, EVERY PROJECT SERVES TO DEVELOP A CLINICALLY APPLICABLE OR DELIVERABLE. USEFUL DELIVERABLE BUT ALSO SOME NOVEL PARADIGM OR PLATFORM TECHNOLOGY. HIGHLIGHTS. THERE'S 14 PROJECTS ADOPTED THROUGH SEVERAL PUBLIC SOLICITATIONS THE LAST THREE YEARS, 12 SMALL MOLECULES AND TWO BIOLOGICS. IN THIS TIME FROM A STANDING START AT THE END OF 2009 WE -- THREE DRUGS IN PEOPLE ALREADY, ONE THE CLL PROJECT I MENTIONED, ONE FOR SICKLE CELL DISEASE, ONE OF THE PEOPLE FOR HEREDITARY INCLUSION OFMYOPATHY YESTERDAY. WE STARTED NATURAL HISTORY WORK. THIS COMES FROM OUR VERY CLOSE COLLABORATION WITH OUR COLLEAGUES AT THE FDA WHO POINTED OUT THAT NATURAL HISTORY, AND WHAT GOES WITH IT, REGISTRY, BIOBANKS, ET CETERA, CLINICAL OUTCOME MEASURES LIMIT IT IS ABILITY OF PROJECTS TO MOVE FORWARD. SO WE'RE DOING NATURAL HISTORY WORK. EVERY PROJECT IS A UNIQUE USUALLY PUBLIC PRIVATE PARTNERSHIP, ESPECIALLY WHEN DONE WITH COMPANIES. THIS WAS REQUIRED A LOT OF REALLY INNOVATIVE PARTNERING WORK DONE MAINLY BY LILY PORTIA YOU HEARD BEFORE. HERE IS WHAT THE PORTFOLIO LOOKS LIKE FROM TREND. PARTNER TYPES, IN THIS CASE HALF BIOTECH, HALF ACADEMIC, AGENTS REPURPOSE DRUGS OR NEW MOLECULAR INTI ITYS -- ENTITIES. OLIGOOR PROTEIN. AND AGAIN, A THERAPEUTIC AREA IS A VERY BROAD NEUROLOGIC DISEASE MUSCLE DISEASE, HEMATOLOGIC DISEASE, MENTAL RETAR DPAITION, ET CETERA, YOU MIGHT ASK WHY ARE WE DOING THIS WIDE SWATH OF DISEASES, THE REASON IS, WE'RE TRYING TO DISCOVER GENERALLY APPLICABLE PRINCIPLES. IF YOU WANT TO DISCOVER PRINCIPLES WHICH ARE GENERALLY APPLICABLE, YOU HAVE TO LOOK ACROSS THE ENTIRE SPECTRUM. THIS IS ALSO HELPED US TO IDENTIFY TARGETS WHICH ARE COMMON TO MORE THAN ONE DISEASE. WHICH IS ALSO TREMENDOUS ADVANCE FOR US. THIS IS ONE EXAMPLE, REDUCE IT TO PRACTICE FOR YOU. THIS IS ONE OF MY FAVORITE PROJECTS FOR ALL KINDS OF REASONS. I'LL SPEND A MINUTE TELLING YOU ABOUT IT. THIS IS THE COLLABORATION WITH A SMALL BIOTECH IN BOSTON NAMED SRX. THE COMPOUND WHO ARE MEDICINAL CHEMISTS IS FRIGHTENING AT BEST. THIS IS THE COMPOUND. IF THERE WERE ANY MEDICINAL CHEMISTS IN THE GROUP THEY WOULD BE SEIZING IN AT THE MOMENT. THIS IS A FRIGHTENING COMPOUND FROM DIFFERENT CHEMICAL SPACE THAN NORMALLY SEEN. ITS MECHANISM OF ACTION IS A BIT FRIGHTENING, IT BINDS THEREFORE IT ALLOWS YOUR SICKLE PHYSIOLOGY ALLOWS THE SICKLE ERYTHROSITES TO GET THROUGH THE EYE POTTIC POST VAK CIEWL WITHOUT SIGNALING SO IT ADDRESSES THE FUNDAMENTAL DEFECT IN SICKLE CELL DISEASE, IN CASE ANYBODY AT HOME IS KEEPING TRACK. THE ORIGINAL MOLECULAR DEFECT IN SICKLE CELL DISEASE WAS DISCOVERED IN 1949. AND WE STILL DO NOT HAVE A DRUG BASED ON THAT KNOWLEDGE. THIS WILL BE THE FIRST DRUG TO DO THAT. DESPITE ALL OF THIS, DESPITE THE HUGE MEDICAL NEED, 80,000 PATIENTS IN THIS COUNTRY, MILLIONS OF PATIENTS WORLDWIDE, NOBODY TOUCH THIS IS. WHY? VERY SIMPLE. CHEMICAL RISK, TARGET RISK, CLINICAL RIS RISK, REGULATORY RISK. PEOPLE COULDN'T MAKE A BUSINESS CASE TO ADOPT THE DRUG DESPITE ITS IMPORTANCE SO WE DID THE ANIMAL TOX STUDY, THE REGULATORY INTERACTIONS WITH FDA. IN A YEAR FROM SIGNING THE AGREEMENT WE WERE PATIENTS. SO THIS WAS DOABLE BASED ON TEAM MODEL AND WE WENT INTO PATIENTS LAST DECEMBER, NORMAL VOLUNTEERS IN DECEMBER NOW END PATIENTS NOW. SO THAT WAS A VERY FAST TOUR THIS WHOLE DIVISION IS FOCUSED ON INNOVATION, PARTNERSHIP DOING THINGS DRCHLY, RAPIDLY STAYING FOCUSED ON THIS. IT'S ADVANCED. SO I'LL STOP THERE. THANK YOU. [APPLAUSE] >> GREAT TOUR. LET'S OPEN UP TO COMMENTS. FRANK. >> I WOULD LIKE TO MAKE A COMMENT, CHRIS. AT LUNCH BERNARD GAVE ME AN INSIGHT WHICH I THINK YOUR PRESENTATION REALLY REFLECTS. AND WHAT HE BASICALLY SAID IS WE HAVE TO THINK ABOUT TRANSLATION HAVING TWO PARTS THERE IS TRANSLATION LEVEL KNOWLEDGE AN DEVELOPMENT OF PRODUCTS AN SERVICES FROM THAT KNOWLEDGE. THE REASON I MENTION IS I THINK YOUR PRESENTATION SHOWED BOTH PARTS OF IT, LIKE TO OFFER THAT THE LINKS WE SAW THIS MORNING A LOT OF WHICH WAS DEVELOPING TRANSLATION OF KNOWLEDGE WITH PARTS OF PARTICULARLY THE EXAMPLES YOU GAVE OF DEVELOPING PRODUCTS AND SERVICES FROM TRANSLATIONAL KNOWLEDGE. >> OTHER QUESTIONS OR COMMENTS. >> UNDERSTANDING HOW THE BUSINESS ENDEPLOYMENT MODEL WORKS SO TAKE TREND, I UNDERSTAND HOW COLLABORATION WITH BIOTECH COMPANY WOULD GET THIS COMPOUND TO PATIENTS BUT THE MAJORITY OF COLLABORATIONS WERE WITH OTHER ACADEMIC INSTITUTIONS OR NIH INTRAMURAL GROUPS. HOW DOES THAT GET A THERAPY INTO THE PATIENT? >> YOU WALKED RIGHT INTO MY TRAP. I THINK THE ANSWERS ARE THE CTSA PROGRAM. THE ONLY PROGRAMS WHICH HAVE OFFICIALLY GOTTEN IN TO THE COMMERCIAL SPHERE ARE PROGRAMS THAT STARTED WITH COMMERCIAL PARTNER. AND FREQUENTLY ESPECIALLY THESE DAYS, IN ORDER TO ATTRACT A COMMERCIAL PARTNER YOU HAVE TO SHOW SAFETY AND EFFICACY OF PEOPLE. DIDN'T USE TO BE THIS WAY 3, 4 YEARS AGO BUT NOW IT REALLY IS. THERE ARE CASES WHICH WE HAVE BEEN ABLE TO ATTRACT COMMERCIAL PARTNERS TO LICENSE THESE, THE PK EXAMPLE IS A GREAT EXAMPLE. I CAN THE TELL YOU WHO THE COMPANIES ARE, BECAUSE THEY'RE PUBLIC NOW. IT'S (INDISCERNIBLE) WHICH ARE TWO COMPANIES IN BOSTON. I WOULD SAY FOR THE MOST PART THESE ARE PROJECTS WHICH NEED BIT MORE WORK AFTER THE LEAD UP STAGE, AFTER THE LEAD DISCOVERY STAGE BEFORE ATRACKED TO THE COMMERCIAL SECTOR. THAT WAS WHY TREND WAS CREATED, THE PROBLEM IS IMPEE DENSE MISMATCH. THERE'S 240 PROJECTS AT THE BEGINNING AND 25 IN TREND. NOT EVERYTHING IS GOING TO REACH THAT POINT BUT THAT'S A REASON I'M SO EXCITED ABOUT THE CTSA PROGRAM. BECAUSE IF YOU LOOK AT THE -- YOU CAN TELL FROM THE TALKS THIS MORNING, IF YOU LOOK AT CENTER OF GRAVITY FOR DPI IS OFF TO THE LEFT. THE CENTER OF GRAVITY FOR DCI IS TO THE RIGHT. THEY ARE NOT MUTUALLY EXCLUSIVE THERE IS OVERLAP BUT THEY'RE COMPLIMENTARY ORGANIZATIONS SO THAT'S WHY I'M EXCITED BECAUSE IF WE COMBINE THE POWER OF THESE TWO GROUPS WE CAN DO IMAGINE CL THINGS IN A BIG HURRY. >> RELATED QUESTION THAT WASN'T CLEAR TO ME, HOW YOU GO ABOUT THE PROJECT OR DISEASE SELECTION. YOU ONLY HAVE $20 MILLION. >> IT'S -- THERE'S A REVIEW GROUP 20 REVIEWERS, ALMOST THE VAST MAJORITY FROM BIOTECH AND BC, SOME OF YOU HAVE SEARCHED ON SOME OF THOSE SELECTION COMMITTEES. AND THEN GOES TO A SECOND LEVEL REVIEW COMES BACK TO THE COUNCIL. >> WHERE DO THE IDEAS GENERATE FROM, A DISEASE, YOU THINK A -- PICK A DISEASE AN TRY TO FIND -- >> NO. THIS IS -- >> HOW WOULD THOSE BE -- >> THERE'S ABOUT OPEN SOLICITATION. EACH TIME FOR TREND WE HAVE GOTTEN 65 APPLICATIONS EACH TIME IVE ABLE TO CHOOSE FOUR. SO THE SUCCESS RATE IS EXTRAORDINARILY LOW. THE RESOURCES ARE LIMITED. THERE HAVE BEEN SUGGESTIONS. THIS IS SOMETHING THIS COUNCIL OUGHT TO THINK ABOUT AND ADVICE US ON. A NUMBER OF PEOPLE IN BOTH ACADEMIC SECTOR AND PRIVATE SECTOR HAS SAID REALLY WHAT YOU OUGHT TO DO IS HAVE SOME WAY FOR THESE PROGRAMS TO DO WHAT YOU'RE SUGGESTING WHICH IS TO IDENTIFY PUBLIC HEALTH NEEDS OR RARE DISEASE NEEDS OR OPPORTUNITIES AND GO OUT AND SOLICIT. WE HAVEN'T DONE THAT SO FAR. SO FAR THERE ARE SO MANY NEEDS THAT WE HAVE BEEN ABLE THE NOR THAN FILL OUR QUEUE WHAT COMES IN THE DOOR FROM UNSOLICITED -- FROM A OPEN SOLICITATION. >> >> YOU SPOKE ABOUT PARTNERSHIP WITH FDA POSITIVELY. I WONDER IF YOU CAN TALK ABOUT THAT. THAT'S NOT THE EXPERIENCE PEOPLE HAVE ALWAYS. I WONDER IF THE FACT YOU'RE A SISTER AGENCY WITH RECOGNIZED EXPERTISE HELPS MOVE THE PROCESS ALONG FASTER OR IS IT SOMETHING ELSE? >> IT'S A GREAT QUESTION. I THINK SOME OF IT IS THE FACT THAT WE ARE A SISTER AGENCY. I ALSO THINK A LOT IS WE WENT TO THEM WITH A VERY GENERAL QUESTION AS WELL AS SPECIFIC QUESTIONS, WE SAT DOWN WITH THEM IN 2009 AND ASKED THEM, THESE ARE FOLKS WHO USED -- I DON'T KNOW IF YOU KNOW ANN AND MARK BUT THEY USED TO BE IN REVIEW DIVISIONS BUT ONE IS NOW OFFICE OF TRANSLATIONAL SCIENCE AND NEW DRUGS AN RARE DISEASES SO THEY ARE NOT THEY DON'T HAVE A CONCERN OF BEING REVIEW PEOPLE SO THEY GIVE US GENERAL ADVICE. YOU SEE MANY, MANY, MANY PROJECTS. WHAT ARE THE FACTORS THAT HOLD BACK RARE DISEASE DRUG DISCOVERY IN YOUR EXPERIENCE? WHEN PROJECTS COME IN, WHAT ARE THE TOP THREE THINGS THAT ARE -- PREVENT THESE PROJECTS FROM BEING SUCKSISFUL? FRANKEDLY -- THE CHEMISTRY ISN'T RIGHT OR THE ASSAY THEY USE WASN'T RIGHT, NOT THE RIGHT TOX STUDY. WHAT THEY SAID IS, TOP THREE ARE LACK OF NATURAL HISTORY, LACK OF NATURAL HISTORY AND LACK OF NATURAL HISTORY. THAT WASN'T EVEN ON MY RADAR SCREEN. AS I ASKED THEM TO EXPLAIN THAT, IT'S NOT LACK OF NATURAL HISTORY, WHICH IS IMPORTANT FOR RARE DISEASE BUT THAT LEADS TO DIAGNOSTIC CRITERIA, CLINICAL OUTCOME, BIOMARKERS, REGISTRIES, ET CETERA, ET CETERA. THEN WE ASKED WELL, SHOULDN'T TREND WORK THIS IN THIS ARENA. IF TREND IS COMMITTED TO GETTING DRUGS ACROSS THE GOAL LINE TO PEOPLE THIS IS THE BIGGEST FACTOR THERE IS. WE HAVE TO WORK ON THAT. SO THERE HAVE BEEN BIG ISSUES LIKE THAT. WE HELD A SYMPOSIUM HOW TO WORKING ON IMPLEMENTING IT NOW. TOGETHER WITH OTHER INSTITUTES. BUT THE OTHER ISSUES HAVE BEEN SOMETHING THAT NOW WE KNOW IT WORKS, NOW THAT NCATS IS NCATS. I CAN SAY THAT NCATS IS GOING TO DO THIS. AS OF TEN DAYS FROM NOW, THE OTHER ASPECT THAT IT'S BENEFITED US TREMENDOUSLY IS THE ABILITY TO SIT DOWN WITH TWO PEOPLE AT FDA WHO ARE TREMENDOUSLY EXPERIENCED AND SAY LOOK, HERE IS A PROJECT. HERE IS THIS CLL PROJECT. WE SAID WHAT ARE WE NOT THINKING OF? WHAT IS GOING TO COME HIT US LIKE A TRAIN THAT WE'RE NOT LOOKING FOR? THAT WAS UNBELIEVABLY HELPFUL. WHEN WE WENT FINALLY WITH OUR PRE-ID MEETING, WE HAD A LOT OF KNOWLEDGE GOING INTO THAT. THAT WE OTHERWISE WOULDN'T HAVE HAD. AND REALIZE THAT ALL THE PEOPLE ON THIS PROJECT TEAM ALL COME FROM PHARMA AN BIOTECH. SO WE THINK WE ACTUALLY KNOW SOMETHING ABOUT THIS. WE HAD A LOT TO LEARN. SO WE HAVE HAD ACCORDINGS ABOUT HOW TO GENERALIZE THAT, HOW DO WE MAKE ADVICE AVAILABLE TO PEOPLE WHO NEED IT AND THEN WE GET INTO ISSUES OF MAN POWER AND ALL OF THAT. THIS IS REALLY IMPORTANT. PEGGY WAS TALKING ABOUT IT. SHE'S NOT HERE BUT SHE WAS TALKING ABOUT IT BEFORE. I THINK THAT'S SOMETHING NCATS ADAPTER FUNCTION NEEDS TO LOOK AT. A LOT OF US FIND INVESTIGATORS -- WE HAVE A NUMBER OF PROGRAMS THAT COME BECAUSE OF THIS. INVESTIGATORS WHO DON'T KNOW HOW FDA WORKS AND DOESN'T KNOW WHAT THEY REQUIRE, THEY WILL PUT IT IN AN NIMD, WE HAVE ONE WITHOUT HAVING THE DATA THEY NEED. WE LITERALLY HAD AN INVESTIGATOR WE CURRENTLY WORK WITH WHO WENT TO FDA WITH AN IND NOT REALIZING THE TOXICITY DATA WAS NEEDED. WHEN THE FDA WROTE THEM BACK AND SAID NO, YOU NEED TOX DATA HE WROTE AN IRATE LETTER TO THE HEAD OF FDA. SAYING THAT IS AN OUTRAGE. THIS IS COMPLETELY ARBITRARY, WE FIXED IT NOW BUT THAT IS A RELATIVELY SIMPLE PROBLEM TO SOLVE. IT'S GREAT FOR NCATS TO DO. >> WE NEED TO MOVE ON, SCOTT, GIVE YOU THE LAST COMMENT OR QUESTION. >> CHRIS DESCRIBED THE COLLABORATION THAT WE HAVE WITH LEUKEMIA LYMPHOMA SOCIETY AND N CATS AND KU. WE INTENTIONALLY NAMED THE COLLABORATION, THE LEARNING COLLABORATIVE. WE HAVE PROJECT MANAGER IN EACH OF THE ORGANIZATIONS WORKING TOGETHER AND TO HIRE CHECKING AL THESE LEARNINGS. ONE LEARNING THAT'S FALLEN OUT AND TIES BACK TO POLICY DISCUSSION THIS MORNING IT WORKS WELL FOR NEW INDICATION. WHAT IF THE PRODUCT THE GENERIC PRODUCT, STRENGTH, ET CETERA, WORKS FINE. THERE IS NO EXCLUSIVELY PATH. THERE IS NO OPPORTUNITY TO BRING A FOR PROFIT PARTNER IN TO INVEST IN THOSE TRIALS. SO ONE OF THE THINGS THAT ONE OF THE LEARNS THAT'S DAWNED ON US AND I THINK WE AFFECTIONATELY CALL THIS THE PUBLIC HEALTH OPTION, IS REALLY CAN CAN WE DEVELOP GUIDELINES AROUND WHAT DATA WOULD BE REQUIRED TO BE ABLE TO PROVIDE HEALTHCARE PROVIDERS WITH INFORMATION THEY NEED TO PRESCRIBE THE DRUG OFF LABEL AND THEN WHAT SORT OF DATA NEEDS TO BE GENERATED IN TERMS OF REIMBURSEMENT. SO WANT TO POINT THAT OUT AS LEARNINGS WE HAVE TAKEN AWAY. >> ONE REASON WE CHOSE THIS PROJECT WITH WE KNEW WE WERE GOING HAVE TO CONFRONT THAT ISSUE. SO IF WE HAD BEEN IN BUSINESS WE WOULD HAVE SAID THERE'S NO WAY WE KNEW THE REIMBURSEMENT WOULD BE ISSUE, WE KNEW EXCLUSIVITY WOULD BE AN ISSUE. SOMEBODY HAS TO SOLVE THAT PROBLEM. SO WE TOOK IT ON FOR THAT REASON. NCATS HAS THE OPPORTUNITY TO ADDRESS PROBLEM, TAKE ON PROJECTS. FOR COUNTER INTUITIVE REASONS. >> IT'S A CLARIFICATION BECAUSE OF WHAT WAS JUST SAID. JUST TO CLARIFY, IF YOU6 TAKE A DRUG THAT'S OFF PATENT AND DEVELOP A NEW INDICATION APPROVED YOU CAN GET EXCLUSIVITY FOR MARKETING INDICATION. THE TROUBLE IS PILE IN AND TAKES ADVANTAGE OF IT. IT'S NOT -- THE MODEL FDA IS BUILT, MARKET EXCLUSIVITY, DOESN'T WORK. ANTIBIOTICS IS AN EXAMPLE WHERE YOU CAN'T COME UP WITH A BUSINESS MODEL FOR DEVELOPING A DRUG THAT ACTUALLY WE DON'T WANT TO USE, WE WANT TO HOLD IN RESERVE AS LAST RESORT DRUG. IT DOES STRIKE ME AS AREAS THAT WOULD BE WORTHY OF CONCENTRATION WHICH IS IDENTIFYING THOSE PARTICULAR BUSINESS AREAS WHERE THE CURRENT MODEL BASED ON EXCLUSIVITY, DOESN'T WORK FOR CONSUMERS OR COMPANIES AND THEN EXPLORE THE OPTIONS. THE (INAUDIBLE) TALKING ABOUT MILESTONES AWARDS, ET CETERA. BUT CLOSE THOSE GAPS FOR THE COMPANIES AN GIVE THEM A WAY FORWARD. >> >> I CAN TO SAY YOU CAN GET INTELLECTUAL PROPERTY PROTECTION AND EXCLUSIVITY, GOOD EXAMPLES THROUGH IT WHICH MANY YEARS WAS -- TOXICITY IS NOW A VERY IMPORTANT DRUG, CANCER. BUT I THINK THE ISSUE IS REALLY MARKETING. I DON'T THINK REIMBURSEN'T IS AN ISSUE, IF IT'S A GENERIC DRUG IT'S PENNIES. SO THE ISSUE IS HOW TO DISSEMINATE INFORMATION AND MARKET THE PRODUCTS IN PUBLIC HEALTH SETTING. THAT'S VERY COMPLEX ISSUE. EASIER FOR VACCINES BECAUSE CDC YOU CAN SAY USE THIS VACCINE FOR THIS CONDITION, EVERYBODY SHOULD GET THE DRUG. BUT WHEN IT COMES TO MEDICINAL THERAPIES PHARMACEUTICAL MARKETING IS PROBABLY WHAT IS MISSING IN THE PUB HICK HEALTH SECTOR FOR GENERIC MEDICINE DEVELOPED BY NCATS. IT WOULD BE A CHALLENGE BUT IMPORTANT FOR THIS ORGANIZATION TO THINK ABOUT. >> IS THIS THE PLACE THAT YOUR SHOP SHOULD BE THINKING ABOUT WORKSHOP OR (INAUDIBLE)? >> POLICY WORKSHOP IN OCTOBER, ONE IS ISSUE OF INTELLECTUAL PROPERTY FOR REPURPOSING AND FOR DRUG RESCUE. HOPEFULLY HAVE MORE FULL CONVERSATION ABOUT THIS AND CERTAINLY CONSIDER TACHI ON THE IDEAS YOU RAISE AS WE. >> WE NEED TO MOVE ON, THERE'S TWO KEY PIECES FOR THE AGENDA. IF WE HAVE TIME AT THE END WE'LL CIRCLE BACK TO SOME OF THESE ISSUES. WHEN I MENTION THIS MORNING, TERRIFIC OVERVIEW. WE HAVE A SENSE OF TWO DIVISIONS ABOUT WHAT'S BEEN GOING ON. WE'RE TALKING ABOUT YOUR CHARGE AND ONE THING IS A SECOND TIER REVIEW VERY IMPORTANT PROVIDING GUIDANCE FOR US EQUALLY IMPORTANT, AND IN THAT ROLE WE WILL PRESENT TO YOU ANY CONCEPTS THAT ARE DEVELOPING POTENTIAL FUTURE RFAs. WE HAVE A CONCEPT TODAY AS A TRIAL RUN HERE. THESE ARE CONCEPT WHICH IS THERE HAS BEEN NO FINAL DECISION MADE. THIS IS SOMETHING WE'RE LOOKING FOR FEEDBACK ABOUT AS IT DEVELOPS. AS JANE IS HOLDING UP, IT'S IN YOUR FOLDER. THIS IS THE VANA WHITE MOMENT WHEN JANE HOLDS THE SHEET TO SHOW YOU WHAT IS AVAILABLE. BUT JOCIE WILL TAKE US THROUGH THIS QUICKLY BECAUSE IT'S RELATED TO THE CTSAs. AND ONE FUNCTION THAT WE'RE DEVELOPING WITH THEM. >> SO AS WE TALKEDDED ABOUT THIS MORNING, AS IT RECURRED THROUGH OUR CONVERSATIONS ALL DAY, INCLUDING HOW DOES ONE BETTER ENGAGE COMMUNITIES, PATIENTS AN HEALTHCARE PROVIDERS. CTSAs HAVE ACTUALLY HAD A REASONABLY SIZABLE INVESTMENT IN THIS AREA. BUT AS I LOOK ACROSS THE PORTFOLIO OF CTSA WORK I FELT THIS AN AREA THAT NEEDS STRENGTHENING. THE CTSAs WERE ALL MANDATED TO HAVE A KEY FUNCTION IN -- FOCUSING ON COMMUNITY ENGAGEMENT IN THEIR APPLICATIONS. IMBEDDED IN THEIR APPLICATIONS TYPICALLY WE'RE NOT RESOURCES AND SERVICES FOR COMMUNITY ENGAGEMENT BUT PROJECT. PROJECTS ENDED UP BEING CONSIDERED AND REVIEWED IN THE CONTEXT OF THESE LARGE AWARDS AND NOT COMPETITIVELY EVALUATED LOOKING AT OTHER COMMUNITY ENGAGEMENT PROJECTS. MANY OF THEM WERE GENERIC IN THE SENSE THEY DIDN'T TAKE ON A SPECIFIC DISEASE AREA OR PARTICULAR RESEARCH PROBLEM AND DEVELOP A SOLUTION. IN FACT, A LOT SEEM TO DEAL WITH THE TOWN GOWN PROBLEM THAT MANY ACADEMIC MEDICAL CENTERS HAD. AND AS I LOOKED AT WHAT THEY ACHIEVED I WAS LEFT THINKING THERE'S PROBABLY A PROBLEM IN THAT INSTITUTION. THINKING ABOUT HOW KEY FOCUS IS THE PEER REVIEW POSSESS. THE BUSINESS OF ASKING FOR INNOVATIVE IDEAS, AND THEN HAVING A PANEL, LOOKING AND COMPARING APPLES WITH APPLES, LOOKING AT SIMILAR PROJECTS, AND COMPETING WORK IN THIS AREA WOULD BE A WAY TO BRING AND ENCOURAGE INNOVATION. ALSO COME TO FEEL THAT OUR CONCERN ABOUT DISSAL PARTS OF TRANSLATION IS AN IMPORTANT PART OF THIS INVESTMENT. DEVELOPING SOLICITATION ON THE STREET WE PUBLISHED AN RFI. I WILL TELL YOU WE HEARD MORE ABOUT COMMUNITY ENGAGED IMPORTANCE OF COMMUNITY ENGAGEMENT PATIENT ENGAGEMENT IMPROVING DISTAL TRANSLATIONAL PROCESSES THAN WE DID ON ANY OTHER TOPIC. WE ARE TRYING ENGAGE IN ACTIVE DIALOGUE OVER NEXT FEW MONTHS. COMMUNITY ENGAGEMENT PART OF THE CTSA PROGRAM. AS ONE STEP DOING THAT, I HAVE ESTABLISHED A SMALL WORKING GROUP OF PEOPLE FROM THE MAJOR INSTITUTES WHO HAVE PROGRAMS THAT ATTEMPT TO STRENGTHEN DISSEMINATION IMPLEMENTATION POPULATION BASED RESEARCH. THAT WORKING GROUP COLLECTING SET OF QUESTIONS AND IDEAS NIH INSTITUTES AND CENTERS LIKE TO SEE HAPPENING THAT ISN'T HAPPENING. WHAT ARE RESEARCH PROBLEMS THEY FEEL THEY CAN'T TAKE ON EFFECTIVELY BECAUSE OF NEEDS IN THIS DISTAL PART OF THE TRANSLATIONAL ARENA. THE RFI, WE WILL BE PUBLISHING RFI ON THIS TOPIC. WE EXPECT IT TO BE IN THE GUIDE ABOUT TWO OR THREE WEEKS AND WE WILL BE SOLICITING IDEAS AND INPUT. THEN WE PROPOSE SOMETIME AROUND CHRISTMAS TIME OR SO TO ISSUE A RELATIVELY FOCUSED SMALL SOLICITATION AND HAVE A PANEL SIT AND LOOK AT WHAT IDEAS ARE BEST. I SEE THIS COMING FROM WITHIN THE RESOURCES ALLOCATED TO THE CTSA PROGRAM. BUT AS A WAY TO ENCOURAGE AND STIMULATE THE INNOVATION OF THIS PART OF THE CTSA. INVESTMENT. WE HAVE WRITTEN THINKING ABOUT THE THINGS THAT MIGHT HAPPEN IN THE DISTAL PART OF THE TRANSLATIONAL SPECTRUM. I'M EAGER TO HEAR THOUGHTS AND COMMENTS FROM ALL OF YOU. >> REPRESENTING THE PATIENT COMMUNITY, WE THINK IT'S VERY IMPORTANT OBVIOUSLY. THERE ARE AS MANY OF YOU KNOW MANY DIFFERENT ENTITIES IN GOVERNMENT AND NOT NOW VERY INTERESTED IN PATIENT ENGAGEMENT AND ALL -- OFTEN IN SILOS TRYING TO FIGURE HOW TO DO THAT. SO I WOULD JUST OFFER AND I WILL SHARE WITH YOU OR WITH THE GROUP WE HAVE DONE INTENSIVE WORK AND HAVE COMMUNICATED WITH FDA, PCORI, PHARMACEUTICAL COMPANIES, SOME IDEAS WHERE AND HOW TO ENGAGE PATIENTS INDIVIDUALLY OR PATIENTS ORGANIZATIONS THAT REPRESENT PATIENTS FROM THE BEGINNING TO THE END. SO I'M SUPPORTIVE OF THIS AND JUST LIKE TO SHARE THAT WE HAVE MADE PROGRESS HOW TO ORGANIZE IT, THINK ABOUT IT AND LITERALLY FRAME HOW ONE MIGHT DO THIS. >> THANK YOU. >> >> I THINK YOU HAVE TO LOOK AT THE LAST TWO BULLETSCH THIS IS AN IMPORTANT COMPONENT WE OFTEN MISS. LINKED WITH THE SECOND PART, THE APPS THAT ONE CAN USE IN PROGRAMS PARTICULARLY IN UNDERSERVED AREAS WHERE SOME (INAUDIBLE) TOGETHER WITH THE UNIVERSITY MEDICAL CENTERS, THE FOCUS ON THE UNDERSERVED POPULATION IN LINKING THESE TWO BULLETS TOGETHER I THINK WILL MAKE A REALLY TREMENDOUS CONTRIBUTION. >> THANK YOU. WE WOULD HOPE THAT WE ARE AFTER GENERALIZABLE MODEL. WE WANT TO CATALYZE APPROACHES THAT CAN THEN BE USED AND REPURPOSED IN A NUMBER OF SETTINGS. AND THAT WOULD CERTAINLY BE ONE THING WE WOULD HOPE TO ENCOURAGE THROUGH THIS. PLEASE ALL OF YOU MIEWS ON THIS MORE, DON'T MESS AT A TIME SUGGESTIONS. THIS IS A WORK IN PROGRESS. WE WILL BE SOLICITING INPUT AND IDEAS. WE DON'T THINK THIS IS A BIG PROJECT. WE THINK THIS IS A COMPETITION THAT WOULD FUND PROBABLY SMALL RO-1 SIZE PROJECTS BUT HOPEFULLY A SET OF THEM WOULD COLLECTIVELY PROVIDE INNOVATIVE IDEAS IN AN AREA THAT'S REALLY BEEN DIFFICULT FOR A LOT OF US. I FEEL LIKE I'M ALWAYS SAYING THIS. IN THE AREA THOSE PATIENTS THAT OFTEN AT LEAST LIKELY TO BE ABLE TO GET INTO TRIALS, YOU HAVE THE PATIENTS WHOSE MEDICAL CONDITIONS ARE COMPLICATED THEY DONE HAVE HOMOJEEBIOUS FOR OUR TRIAL YET THAT'S EXACTLY WHERE THE DRUGS WILL OFTEN FAIL BECAUSE WE HAVE NOT HAD ABILITY TO ANTICIPATE. IF I WERE TO THINK OF THEM AS A DISTINCT COMMUNITY OF PEOPLE BASICALLY WHO ARE KIND OF NEGLECTED IN THE PRE-MARKET PHASE, FOR ALL SORTS OF PERFECTLY REASONABLE REASONS, TRYING TO FIGURE IF ANYBODY FOCUS IN HOW ONE MIGHT CAPTURE THAT POPULATION BETTER BECAUSE OF THE BENEFITS IT MIGHT ACCRUE IN WHAT WOULD OTHERWISE BE FAILED DRUGS OR COMPLICATED PHASE 4s. >> THIS IS AN AMAZING COUNCIL. ZERO IN IMMEDIATELY ON THE ISSUES THAT WE ARE ALL STRUGGLING WITH. CERTAINLY THIS PROBLEM FAILURE OF EFFICACY TRIALS TO INCORPORATE PEOPLE WITH COMORBIDITIES IS A PROBLEM THAT'S REALLY IMPORTANT. I THINK INDEED IT MAY COME UP IN THIS SETTING, IT MAY NOT NEED TO BE THE ONLY INVESTMENT, THE NIH MAKES IN THIS AREA. BUT I THINK IT IS AN IMPORTANT PART. ONE PART OF THAT IS TRIAL DESIGNS THAT WILL ALLOW SUCH METHODS INCLUDING WAYS TO DO LARGER TRIALS SUB ANALYSES POSSIBLE. BUT THE BIG PROBLEM OF CAPTURING PEOPLE WHO ARE OUTSIDE THE NORMAL NETWORKS THAT RESULT BRINGING PATIENTS INTO TRIALS IS AN IMPORTANT FOCUS HERE. >> I WAS GOING TO SAY THANK YOU. I THINK THIS IS QUITE STIMULATING AND AGAIN WOULD INVITE EVERYONE TO CONTINUE TO PONDER THIS AND SHARE ANY ADDITIONAL THOUGHTS YOU MIGHT HAVE. WE'VE COME TO THE PUBLIC COMMENT. >> I THINK I DO NEED A FORMAL CONCEPT CLEARANCE BECAUSE WE WILL PROPOSE TO MOVE THIS. DO WE NEED A SHOW OF HANDS? >> WE NEED TO HAVE THIS DISCUSSED. WE DON'T NEED A ACTUAL HAND COUNT. >> FINE. >> TYPICALLY WE DON'T. IT'S SOMETHING THAT AS WE GET INPUT WE DECIDE WHETHER -- WHAT HE WAY TO MOVE FORWARD. IT WILL BE POSTED ON THE WEB AND PEOPLE CAN SEND COMMENTS. IF -- WE CERTAINLY HOPE IT'S GOING TO BE AN ACTIVITY WE HAVE TO TAKE A LOOK AT WHAT THE BUDGET IS. WE TEND TO KEEP DISCUSSIONS AT THE CONCEPT LEVEL. ONE OF THE THINGS WE WANT TO DO IS ENSURE THAT PEOPLE IN THE ROOM CAN IN FACT COMPETE. SO IN THE PRE-RFA PHASE WE'RE REQUIRED TO MAKE THE CONVERSATIONS REASONABLY GENERAL. WE'RE HAPPY TO HAVE HERE UNDER INPUT. WE ANTICIPATE THIS TO BE A REASONABLY MODEST PROGRAM FOR SOLICITATIONS EACH YEAR FOR A FEW YEARS. AND TO DO THIS WITHIN THE CONFINES OF THE CTSA PROGRAM. >> THANK YOU, JOCIE. GREAT EXPLANATION. >> NOW WE HAVE COME TO THE PUBLIC COMMENT PERIOD. NERS INTERESTED IN MAKING A COMMENT OR ASKING A QUESTION TO MAKE YOUR WAY TO THE MICROPHONE. PLEASE IDENTIFY YOURSELF AND YOUR AFFILIATION THEN DIRECT YOUR QUESTION TO THE INDIVIDUAL OR THE GROUP AND ASK AWAY. >> MAYBE IN THE FUTURE PERHAPS NOT AT THIS FIRST MEETING. BUT THIS IS A SEGMENT OF THE COUNCIL AND CAN BOARD MEETINGS SO WE WANT TO PRESERVE, IT'S A GOOD TIME TO HEAR FROM PEOPLE NOT ON THE COUNCIL. SINCE WE HAVE A FEW MINUTES LEFT AT THE END, SOME FEEDBACK FROM ALL OF YOU TO FREDA TO ME OR TO FOLKS AT NCATS. COMMENTS, QUESTIONS, THINGS THAT YOU WANT TO MAKE SURE WE GO AWAY WITH. >> I HAVE ONE QUESTION. THE COUNCIL AND THE BOARD ALL MEET SIMULTANEOUSLY OR IS THERE ANTICIPATION THAT THERE WOULD MEET SEPARATELY AT SOME POINT? >> THE STATUTE REQUIRES THAT THE BOARD MEET FOUR TIMES A YEAR, THAT COUNCIL MEETS THREE TIME AS YEAR, SO WITH WE'LL HAVE THE FOURTH MEETING THE CAN BOARD BY PHONE. BUT THE OTHERS WILL BE SIMULTANEOUS. >> I WOULD BE INTERESTED, THIS GOES BACK TO JOCIE'S PRESENTATION, IN THE THINKING BEHIND THE DECISION TO LINK THE CAP FOR THE CTSA BUDGET TO THE OVERALL NIH FUNDING, AND THE PROBLEM OF THE RICH GETTING RICHER AND SOME OF THE OTHER INTERESTING DISCUSSION THIS MORNING ABOUT OVERALL NUMBER OF CTSAs VERSUS HIGHER FUNDING FOR CENTERS OF REAL EXCELLENCE. MORE BACKGROUND WOULD BE HELPFUL TO ME CERTAINLY. >> IT WAS A COMPLEX SET OF INPUTS WENT INTO THIS DECISION. CERTAINLY A NOTION WE HAVE HERE IS THAT THIS IS A MODEL USED FOR LARGE INFRASTRUCTURE AWARDS IN OTHER PLACES. NONE ARE COMFORTABLE WITH THE HISTORICAL GCRC BASED FORMULAS. IT WAS CLEAR IT WAS TIME TO MOVE BEYOND THAT MODEL. THIS IS OF COURSE THE MAXIMUM AMOUNT THAT CAN BE REQUESTED, IT IS NOT THE THE AWARDED LEVEL. IT IS OUR INTENT TO BUILD INTO THIS PROCESSES WHICH ALLOW US CLOSER OVERSIGHT OF HOW DOLLARS ARE SPENT AND HOW IT RELATES TO SERVICES DELIVERED AT THESE SITES. ANDEN I THINK THAT THAT OVER TIME SHOULD DEVELOP SUBSTANTIALLY MORE VARIABILITY IN THE LEVEL OF FUNDING. THE REALITY IS THAT THE INSTITUTIONS THAT HAVE HIGH -- SO ONE THING WE TRACKED WAS SHOULD WE FOCUS THIS ONLY ON HUMAN SUBJECTS FUNDING. AND THE TWO NUMBERS, AND TOTAL NIH FUNDING AND FUNDING FOR HUMAN SUBJECTS RESEARCH TRACK WITH THE EXCEPTION OF A COUPLE OF SMALL RESEARCH INSTITUTES TOGETHER SO CLOSELY DID NOT SEEM ADVANTAGES IN TRYING TO SEPARATE THEM. SO THAT WAS ONE THING THAT WAS CONSIDEREDCH IT IS CORRECT THAT THIS FORMULA DOES RESULT IN LARGE AWARDS TO PLACES WITH A VERY RICH NETWORK FUNDING INVESTIGATORS, WE ARE SETTING INSTITUTIONS THAT ARE SMALLER, WE ARE SETTING MAXIMUM AWARDS SUBMISSION NUMBER OF 4 MILLION. NOW, OVER TIME,FO8 NCATS WILL NO DOUBT NEED TO CONTINUALLY RE-EVALUATE THAT. BUT THAT IS A NUMBER THAT HAS BEEN USED HISTORICALLY THROUGHOUT THE PROGRAM. AS PEOPLE RESPONSIBLE FOR THIS TRANSITION PHASE, WE FELT WE COULD ONLY SHAKE THE TREE SO MUCH. THAT IN ESSENCE MEANS ABOUT THIRD OF THE INSTITUTIONS ARE RECEIVING MORE FUNDING THAN THEY WOULD BASED ON FUNDING BASE ALONE. IT IS IN ESSENCE A COUNTER FORCE TO THE RICH GETTING RICHER. IT IS AN INVESTMENT SMALLER SITES. IT'S BACK TO A QUESTION WE HAVE BEEN TALKING ABOUT TODAY OF METRIC AND HOW WILL AND SHOULD NCATS OVER TIME DEVELOP WAYS TO MEASURE HOW WELL ARE THE FUNDS BEING SPENT AT THESE SITES. I STARTED OUT ENORMOUSLY IMPRESSED AT WHAT WAS HAPPENING AT THE LARGE SITES WONDERFUL THINGS HAPPENING IN SMALL SITES SO I DON'T KNOW. WHAT THE RIGHT MIX IS. PART IS THE BUSINESS OF STRENGTHENING METRICS, THAT'S SOMETHING THAT IS CLEARLY AN ONGOING DISCUSSION AN SHOULD BE HERE. THERE IS NO MAGIC TO THE NUMBER 60 OR 61. AND I THINK ONE OF THE ISSUES THAT THE IOM GROUP WILL BEGIN TO LOOK AT, WHAT IS THE RIGHT LANDSCAPE HERE? SHOULD THERE BE FEWER, MORE, FEWER BIG ONE? HOW TO ACTUALLY GET THE MIX CORRECT. IF IT IS GOING TO BE A NATIONAL NETWORK, WHAT SHOULD THAT LOOK LIKE AND HOW DO WE DEFINE IT? THIS IS THE YEAR BETWEEN NOW AND NEXT JUNE WHEN THE REPORT IS DUE. THIS IS A GOOD YEAR TO BE THINKING ABOUT THOSE ISSUES, GETTING INPUT. CLEARLY MAJOR ISSUE FOR COUNCIL NEXT COUPLE OF MEETINGS. >> I WOULD LIKE TO PERHAPS THE ONE USE THE WORD STRESS BUT RESTATE THE COMMENT I MADE THE INCITE FROM BERNARD. BECAUSE FROM YOUR PRESENTATION, CHRIS, I GOT A SENSE YOU WERE CLOSE TO SAYING THAT BUT REFRAINED. THERE IS A POTENTIAL HERE WHERE THE CTSAs COULD FOCUS 60 TO 70% OF THEIR EFFORT ON THE DEVELOPING TRANSLATION KNOWLEDGE AND DPI FOCUSES 60 OR 70% DEVELOPING PRODUCTS FROM THE KNOWLEDGE. THRAI DO BOTH BUT THAT IS WHERE THE EMPHASIS IS. IF ONE DOES THAT, THE ISSUE METRICS BECOME EASY, EASIER IN THAT YOU CAN DEVELOP METRICS FOR EACH OF THOSE ACTIVITIES. AND I THINK ALSO AN EXPLANATION TO THE PUBLIC IN TERMS OF WHAT THEY'RE GETTING FOR THE MONEY BEING SPENT BECOMES EASIER. SO I WANTED TO REPEAT THAT. YOU MENTION THIS, IT WAS REALLY INSIGHT THAT HELP ME SORT OUT THE STRUGGLES I HAD THIS MORNING WITH THE WONDERFUL WORK BEING DONE. NO QUESTION. EXTREMELY GREAT WORK BEING DONE. BUT STILL ASKING MYSELF OKAY, AS THE PATIENT AS THE PUBLIC WHAT'S COMING OUT OF THIS, THAT I COULD POINT TO. SO IT'S A VERY HELPFUL (INAUDIBLE). >> MARCH GREAT GET. >> TO PICK UP ON THAT THEME, I THINK THE POINT THAT I WANT TO STRESS IS MORE THE MACRO THREAFL THAT RELATES TO WHAT YOU SPOKE OF, FRANK, IT'S COMMUNICATION. IF WE CAN'T COMMUNICATE EFFECTIVELY ABOUT WHY NCATS IS ADDING VALUE, TO THE THORNY ISSUES THAT VEX THE SYSTEM AND HOW THERE REALLY ISN'T A SYSTEM, WE HASN'T HOPE FOR BUDGET INCREASES, ET CETERA, ET CETERA. THE WAY NCATS WAS ABLE TO BE CREATED QUITE FRANKLY I THINK BECAUSE WE SAID IT WAS BUDGET NEUTRAL. WE WERE JUST THREADING THE NEEDLE OF EXISTING ASSETS. SO NOW IN ORDER TO BUILT A CASE OF OKAY, YOU HAVE GOT TO GET IN MORE MONEY BEYOND WHAT THE PRESIDENT'S BUDGET IS, I THINK IT'S GOING TO HAVE TO BE BECAUSE WE'RE DOING X, Y AND Z AND WE CAN'T TALK SPECIFIC PROJECT, WHY IS IT ADDING VALUE WHY ISN'T IT HAPPENING IN THE PHARMACEUTICAL SECTOR OR PHARMACOLOGY, I RECEIVED THE EMAIL THET OMB REPORT HAS COME OUT AND IT'S SLATED THAT NIH IS GOING TO TAKE AN 8.2% CUT IF SEQUESTRATION OCCURS SO I WANT TO BE MINDFUL OF HOW WE TALKED ABOUT WHAT NCATS IS GOING GOING FORWARD. >> LOR RA. >> I WAS INTERESTED TO HEAR THE CONVERSATION ABOUT THE METRICS AND THE EVALUATION BECAUSE BEING IN A CTSA PROGRAM WE TRY TO SPEND OUR TIME TO TRY TO ARTICULATE THE DIFFERENCE THAT YOU HAVE MADE. AND I THINK THE FRUSTRATION THAT YOU HEAR, WHY DON'T WE HAVE BETTER METRICS, A LOT OF THAT IS FRUSTRATION BECAUSE OF THE DIVERSITY OF THIS CTSA PROGRAM. EVERY CTSA PROGRAM IS DIFFERENT AND THEY HAVE DIFFERENT FOCI. TO TRYING TO GET UNIFORM METRICS TO COVER FOCI IS VERY DIFFERENT. NOW YOU HAVE A SYSTEM WHERE 2.0 WHERE YOU HAVE UNIQUE ASPECTS AT EVERY CTSA IDENTIFIED, EVERY CTSA HAS AN IDENTITY. IT'S THE PERFECT TIME TO HARNESS IT NOW. COME UP WITH SOME UNIFORM MANDATES IF YOU CAN PLAIB IN THIS ARENA, PLAY IN THIS ARENA. IF YOU CAN PLAY IN THIS OTHER ARENA THAT'S TOTALLY DIFFERENT THAT'S YOUR STRENGTH, LET'S GO HERE. BUT THINK ABOUT THE BUDGET IN TERMS OF THIS IS HOW MUCH YOU NEED TO RUN THE RESOURCES, CREATE THE HOME, KEEP EVERYONE GOING. BUT THERE ALSO HAS TO BE THIS MUCH OF WHAT YOU DO CREATING THIS ENGINE. FROM THE ENGINE WHAT WE LEARN ABOUT DEVELOPING THESE METRICS CAN HELP SUPPORT FIRST PART LOCALLY AND HELP DEVELOP THOSE. NOT THE TIME TO HARNESS WHAT'S OUT THERE, LET PEOPLE THEYPLAY TO STRENGTHS BUT BE MORE DIRECTED FROM THIS GROUP WHAT THAT'S GOING TO BE. >> ABSOLUTELY AMAZING TO HEAR YOU SAY THIS. THIS IS THE COMMENT. WE ARE HEARING OVER AND OVER AND OVER AGAIN, FROM THE CTSAs THEMSELVES, SET US FREE. LET US SHOW YOU WHAT WE CAN DO. WE HAVE AMAZING CAPACITY. EVERY ONE OF US IS DIFFERENT. DON'T EXPECT US TO ALL DO ALL THE SAME STUFF ALL THE TIME. IF YOU PUT USING TO AS A NATIONAL PROGRAM WE WILL BLOW YOU AWAY, WE CAN REALLY DO SOMETHING TRANSFORMATIVE AND GREAT. IT'S WONDERFUL FOR US TO HEAR THIS, THE OTHER THING WE HAVE BEEN HEARING AS WELL, PEOPLE ARE SAYING NIH NEEDS TO BE MORE PROACTIVE, GET US TO DO MORE NOT LESS. THERE'S THE SENSE IF ANYTHING PEOPLE FELT WE'RE HOLDING YOU BACK. IT IS AN IMPORTANT MESSAGE FOR COUNCIL TO HEAR AS WELL, THE CTSAs THEMSELVES WANT TO BE QUITE DIFFERENT THAN WHAT THEY HAVE BEEN UP UNTIL NOW. >> CHRIS TALKS ABOUT THE PARTNERSHIP HE'S DEVELOPED FROM A PRE-CLINICAL STANDPOINT. THAT PARTNERSHIP HAS TO BE DEVELOPED FROM THE CLINICAL STANDPOINT NOT ONLY ACROSS THE CTSAs BUT ALSO WITH PEOPLE SITTING IN THIS ROOM NEED TO BE MORE INVOLVED BECAUSE IT'S ONLY WHEN YOU GET THAT REALLY WE'RE WORKING ON THE GROUND BOOT ON THE GROUND INTERFACE THAT'S WHEN IT'S GOING TO HAPPEN. YOU GUYS ALSO HAVE TO DIVE IN WITH US. >> MERRILL, I'M SORRY WE HAD TO SKIP YOU BEFORE. NOW YOU HAVE A CHANCE. >> QUITE ALL RIGHT. I THOUGHT WHAT I HEARD WAS SOMETHING COMPLETELY DIFFERENT THAN WHAT YOU JUST SUMMARIZED. WHAT I THOUGHT, OBVIOUSLY I WAS WRONG, I WAS HEARING KIND OF NODDING WAS YES, THEY'RE DIFFERENT, WE NEED TO LEARN FROM THEM AND LET THE FLOWRS BLOOM BUT NOW IS THE TIME TO HARNESS AND MOVE TOWARDS SOME STANDARDIZATION, BE MORE PROACTIVE AND MANDATING REQUIREMENTS IN AREAS WHERE IT MADE SENSE. IT CAME UP EARLIER, I WAS GOING TO BRING IT UP AND SOMEBODY DID AND PEGGY SAID SOMETHING ABOUT IT. BUT SOME OF US ARE VERY INVOLVED WITH THE MANY SENTINEL PROJECT. WE'RE VERY INVOLVED WITH OMA. THESE ARE ALL AND MANY OTHER, THESE ARE ALL ACTIVITIES TRYING TO HARNESS THE DATA THAT IS OUT THERE, BIG DATA, DATA COLLECTED OTHER WAYS, WE'RE MOVING TOWARD ELECTRONIC HEALTH RECORDS THAT NEED STANDARDIZATION. WHAT WE FOUND FROM RESEARCH WE DID WITH PATIENTS AND PATIENTS REPRESENTATIVE, FAMILY CARE LIVER GIVES, -- CAREGIVERS. ONE OF THE TOP FOUR THINGS PATIENTS WANT ELECTRONIC HEALTH RECORDS TO BE USED FOR RESEARCH. SO HERE WE HAVE ALL THESE ISSUES HOW CAN WE GATHER INFORMATION IN A STANDARDIZED WAY WHERE WE CAN RESEARCH ONCE THINGS HIT THE MARKET, IN MULTIPLE WAYS ACROSS HUGE NUMBERS THAT. IS THE OPPOSITE OF WHAT YOU SAID WHICH IS LET THEM GO FREE SORKS I'M -- I THINK IT'S GREAT TO LEARN AND HAVE THAT BALANCE BUT I THINK IT IS -- WHAT I THOUGHT I WAS HEARING WAS LET'S HARNESS THE FACT THAT AT THIS POINT WE CAN IDENTIFY NOT EVERYTHING BUT AREAS AND WORKING IN COLLABORATION WITH THESE OTHER INITIATIVES AND LET'S GO OUT THERE AND STANDARDIZE SOME THINGS THAT WILL HELP MOVE RESEARCH FORWARD. >> WE ARE IN FACT TALKING ABOUT SOMETHING DIFFERENT. WHERE THE PROGRAM IS NOW IS CHECKLIST AND ALL 61 SITES HAVE TO DO NINE THINGS AND HAVE TO DO THEM THE SAME WAY. THAT'S PROBABLY NOT ALLOWED THEM TO BE ABLE TO BE AS INNOVATIVE AS THEY COULD BE. BECAUSE EVERY ONE OF THESE SITES IS SO DIFFERENT. SOME WILL BE SPECTACULAR ON COMMUNITY ENGAGEMENT, OTHERS ARE GREAT HIGH THROUGH PUT SCREENING. THERE WILL BE A CORE WHERE STANDARDIZATION CAN TAKE PLACE AND AROUND ELECTRONIC MEDICAL RECORDS AND ISSUES TURNING CLINICAL DATA TO RESEARCH DATA, A GREAT EXAMPLE OF THAT. WHAT I THINK WE HAVE BEEN HEARING TODAY. AND WHAT I TOOK FROM NORA'S COMMENT AND WHAT WE HAVE HEARD FROM SO IN METASTASIS CTSA LEADERSHIP IS WE COULD DO SO MUCH MORE THAN WHAT WE HAVE BEEN DOING THERE ARE TOO MANY TELEPHONE CALL, TOO MANY MEETINGS, TOO MUCH PROCESS. SO THERE'S NOT ENOUGH TIME FOR SUBSTANCE. JOCIE. (OFF MIC) >> I UNDERSTAND HOW IT WAS POSSIBLE THE TO READ THOSE DIFFERENT COMMENTS BUT I ACTUALLY SAW IT AS QUITE COMPATIBLE. WHAT THE NIH HAS TO DO IS TAKE A LARGER ROLE AND FORMULATING SOME GOALS. IT DOESN'T MEAN FOR EVERY GOAL ALL 60 WANT TO PLAY. SO WE MAY HAVE 7 SITES WHO ARE ABLE TO REALLY COME TOGETHER TO DO RARE DISEASE WORK. STANDARDIZATION AND COMMON GOALS ACROSS THAT WILL BE IMPORTANT. SO -- I THINK THAT WHAT I HAVE BEEN HEARING FROM THE CTSAs. IT DOESN'T MEAN ALL 60 WILL BE ALIKE. >> JANE. >> WE'RE AT THE END OF THE DISCUSSION AND I JUST WANT -- BEFORE ANY GAVELS FALL, I WANTED TO BE SURE THAT ALL OF THE MEMBERS AMONG THE IMPORTANT INFORMATION THAT WE HAVE GIVEN YOU, I WANT TO BE SURE YOU FOUND REIMBURSEMENT AND TAKE IT WITH YOU. THAT WILL BE GOOD. >> >> YOU'RE CHANNELING SUSAN'S COMMENT FROM EARLIER TODAY. I CAN TELL MANY HER ABSENSE YOU WANTED TO REPRESENT HER. >> WITH THAT, I WILL OFFICIALLY CLOSE THE CAN. I'M SORRY. THIS IS THE ONE WITH THEBLING BY THE WAY. >> AND NCATS COUNCIL WILL RECONVENE AT 3 O'CLOCK FOR A CLOSED SESSION SO DON'T GO TOO FAR. I THINK BOTH FREDA AND I WERE FEELING THIS WAS A FANTASTIC FIRST MEETING. LOTS TO TALK ABOUT, WE DIDN'T GET EVERYTHING DONE TODAY BUT JUST REALLY WE'RE VERY THANKFUL TO HAVE THIS GROUP SO ENGAGED ON THESE PROBLEMS. AS WE HAVE SAID THROUGHOUT THE DAY, THIS IS JUST AN ENORMOUS RESOURCE, GREAT POTENTIAL HERE FOR US TO CHANGE THE WORLD. AND WE NEED YOUR WISDOM KNOWING HOW TO DO THAT IN THE BEST WAY. SO THANKS. I WON'T BE MEET WITH YOU AGAIN, >> I HAVEN'T SAID YES YT. [LAUGHTER] >> OKAY. I FEEL CAUGHT IN THE MIDDLE OF THAT. SO WHY DON'T I TAKE THE OPPORTUNITY TO THANK TOM. IT WAS WONDERFUL SHARING THIS DAY WITH YOU AND I'M SURE EVERYONE WANTS TO THANK YOU FOR ALL OF YOUR SERVICE BUT IN PARTICULAR FOR SHARING THIS DAY WITH US. SO THANK YOU VERY MUCH. [APPLAUSE] >> NOW I CAN HOLE THE REST OF YOU ACCOUNTABLE FOR WHAT HAPPENS TO NCATS FROM HERE ON. SO I WILL BE WATCHING WITH GREAT ADMIRATION BUT ALSO GREAT EXPECTATIONS. THANK YOU VERY MUCH. WE'RE ADJOURNED.