>> SECOND DAY OF THE NONPROFIT WORKSHOP THANKS TO EYERYONE'S GOOD IDEAS AND DISCUSSION, AND YESTERDAY, THINGS WENT EXTREMELY WELL AND SO TODAY, WE HAVE A BEGINNING SESSION ABOUT THE NIH STRATEGIC PLAN AND THEN THE STEERING COMMITTEE THAT PUT TOGETHER THE WORKSHOP MOSTLY HEADS OF THE NONPROFITS HERE, THOUGHT THAT WE SHOULD REALLY PAY ATTENTION TO DIFFERENT MODELS IN WHICH THE DISEASE ORGANIZATIONS CAN WORK WITH OTHER PARTNERS, INDUSTRY, ACADEMIA, GOVERNMENT TO FOSTER RESEARCH IN THEIR AREAS AND WE BROKE IT DOWN INTO THE MAJOR BINS WE HAVE AT NIH SO BASIC, TRANSLATIONAL AND CLINICAL, THAT'S HOW THINGS GO TODAY AND WE'LL HAVE BREAK OUT SESSIONS IN THE AFTERNOON AND THOSE BREAK OUT SESSIONS FOLLOW ALONG ON THE TOPICS FROM THE MORNING, SO LOTS OF TIME FOR DISCUSSION. THE BREAK OUT SESSIONS WILL REPEAT THEMSELVES IN THE AFTERNOON, SO YOU HAVE TO PICK TWO, UNLESS YOU WANT TO RUN AROUND, YOU KNOW FROM ROOM TO ROOM TO ROOM ALL AFTERNOON. BUT YOU HAVE THE OPTION TO GOING TO ONE AND GOING TO A SECOND OE, THEY'LL EACH BE AN HOUR LONG. SO THE FIRST TOPIC FOR DISCUSSION IS AN IMPORTANT ONE, I IT'S ABOUT THE NIH TRANSLATIONAL RESEARCH TEGGIC PLAN. SO, PROBABLY SURPRISING TO EVERYBODY IN THIS ROOM, EVERYBODY'S NEVER HAD A STRATEGIC PLAN BEFORE. THE NIH OPERATES ON A SYSTEM OF RULES AND TRADITIONS THAT GO BACK QUITE A WAYS AND CONGRESS HAS--I THINK THE TENOR IN CONGRESS IS QUITE FAVORABLE TOWARDS NIH AT THE PRESENT TIME. BUT THERE IS AS WE TALKED ABOUT YAY BEEN A STAG NET FUNDING SITUATION, AND SO ACTIVITY IN CONGRESS TO IMPROVE THE FUNDING AT NIH IS NOW BEING TALKED ABOUT, BUT IT'S NOT BEING TALKED ABOUT AS IT WAS 20 YEARS AGO. SO THE IDEA IS THAT IF NIH FUNDING GOES UP, THEY'RE GOING TO BE REQUIREMENTS TO NIH THAT WERE NOT THERE BEFORE. WE DON'T KNOW EXACTLY WHAT THEY ARE, THERE WILL BE DIRECTIVES FROM CONGRESS ON CERTAIN ISSUES BUT THE FIRST DIRECTIVE TO COME OUT WAS THAT NIH HAS TO SUBMIT A STRATEGIC PLAN AND THAT PLAN HAS TO BE IN BY THE END OF THE YEAR. SO YOU CAN IMAGINE, A LOT OF CONSTERNATION, HOW DOES NIH DECIDE WHAT TO PUT IN SUCH A PLAN, IF NIH DECIDED TO PUT EVERYTHING IN, AND ENUMERATE IT, IT WOULD BE JUST A GIGANTIC LIST OF THINGS AND THE DANGER OF TRYING TO MAKE IT--THE LIST SMALLER AS YOU LEAVE THINGS OUT THAT ARE IMPORTANT. SO INSTEAD NIH DECIDED TO GO WITH A FRAMEWORK WHICH AS WE'LL DESCRIBE TODAY AND THEN LARRY TABAK WILL BE TALKING TOMORROW AT OUR COUNCIL ABOUT IT. AND WITH THE INPUT THAT WE GET, THE NIH WILL WRITE THE STRATEGIC PLAN BASED ON THE FRAMEWORK AND SEND IT TO CONGRESS, SO THIS IS A POINT IN TIME WHICH IS IMPORTANT TO GET THE INPUT FROM THE DISEASE ORGANIZATIONS ON WHAT SHOULD BE IN THE STRATEGIC PLAN AND THAT'S WHY WE THINK IT'S REALLY IMPORTANT TO SPEND TIME ON IT TODAY AND AGAIN TOMORROW AT COUNCIL. SO WITH THAT, I'M GOING TO GO OVER AND HAND THE MIC/FLOOR TO PAUL SCOTT. PAUL S&P DIRECTOR OF OFFICE OF SCIENCE POLICY. SO THE OFFICE, I DON'T KNOW IF PEOPLE KNOW ABOUT IT BUT IT'S AN INCREDIBLY IMPORTANT OFFICE AT NINDS, AND THEY MANAGE ALL IRPT ACTIONS WITH CONGRESS WHICH ARE MANY AND THERE ARE A GROUP THAT CAN BE--CAN TAKE OVER PROJECTS WITHIN THE INSTITUTION AND CHANGE A POLICY, CHANGE PRACTICES AND IMPROVE HOW WE OPERATE AND A REALLY IMPORTANT OFFICE AND PLEASE HAVE PAUL HERE. OKAY, THANK YOU WALTER. GOOD MORNING EVERYONE. I'M HAPPY TO BE HERE THIS MORNING TO GO THROUGH THE NIH STRATEGIC PLAN FRAMEWORK WITH YOU. THE SLIDES I'LL BE USING ARE SET THAT THE NIH OFFICE OF THE DIRECTOR MENTIONED TO US AND DR. MENTIONED THE TABAK, WILL BE GIVING A SIMILAR TALK TOMORROW AT COUNCIL NOW IN THE INTEREST OF TIME, STREAMLINING AND MAKING SLIDES A BIT MORE APPLICABLE TO NINDS, WE HAVE MADE A FEW CHANGES TO THE PRESENTATION. SO THE COP NEUROECTODERMAL YOUR FOLDERS MAY NOT BE THE SAME. SO, WALTER TALKED I LITTLE BIT ABOUT THIS ALREADY, BUT WHY ARE WE DOING THE STRATEGIC PLAN, SO THE CROMNIBUS, PLAN,--YOU ARE FAMILIAR WITH, THE FIVE YEAR PLAN, INCLUDING HAVING MISSION PRIORITY FOCUS AREAS AND RARE AND PEDIATRIC DISEASES AND BIOMEDICAL WORKFORCE ISSUES WERE A PRIORITY. SO, THE GOALS OF THE PLAN THEN ARE TO DEVELOP A LIVING DOCUMENT THAT WILL HELP--IDENTIFY MAJOR TRANSNIH THEMES THAT WILL ADVANCE BIOMEDICAL RESEARCH. IT'S IMPORTANT TO DEFINE WHAT A PLAN SHOULD AND SHOULD NOT BE. SO WHAT NIH IS TRYING TO DO IS ARTICULATE THE HIGHEST PRIORITIES OF THE NIH OVER ALL AND HOW THIS WILL ACHIEVE THE PRIORITIES AND IT SHOULD BE A LIVING DOCUMENT THAT WILL REQUIRE REFINEMENT THROUGHOUT ITS LIFE CYCLE NOW WHAT IT SHOULD NOT BE, AS WALTER MENTIONED IT SHOULD NOT DESCRIBE ALL THE MANY IMPORTANT THINGS THAT NIH DOES AND WILL DO THE IN IF THURE AND THIS IS IMPORTANT AS WELL, IT SHOULD NOT ADDRESS THE PRIMATESSORILITYS OF INDEPENDENT OFFICES ICOs SINCE EACH SHOULD HAVE THEIR OWN PLAN ALTHOUGH THEY'RE REFERENCED IN THE EXECUTIVE SUMMARY. OKAY, SO IN TERMS OF DEVELOPMENT OF THE PLAN, ALL THE ICs AT NIH HAVE BEEN INVOLVED STARTING WITH MEETINGS, SEVERAL MEETINGS OF THE IC DIRECTORS TO COME UP WITH THE INITIAL IDEA AND OUTLINE FOR WHAT THE PLAN SHOULD BE, AND THEN THERE'S A TRANSNIH WORKING GROUP COMPOSED OF POLICY, PROGRAM AND COMMUNICATION STAFF THAT ARE WORKING ON PUTTING IT TOGETHER. THE--DR. COLLINS ADVISORY COMMITTEE TO THE DIRECTOR WEIGHED IN ON SEVERAL TIMES AND GIB A LOT OF FEET BACK THAT RESULT INDEED A LOT OF CHANGES TO IT. AND THIS PAST SUMMER, NIH PUBLISHED THE REQUEST FOR INFORMATION OR RFI, AND THEN ALSO THAT WAS IN JULY, AND THEN ALSO HAD HEALTH WEBINARS IN AUGUST TO GATHER PUBLIC INPUT. SO I'M HOPING MOST OF YOU SAW THE NOTES ABOUT THOSE AND WERE ABLE TO PROVIDE INPUT. AND THEN LASTLY, IMPORTANTLY, NIH IS MONITORING AND OVERSEEING IT IN THE FINAL DOCUMENT. SO THIS IS THE OVERALL FRAMEWORK FOR IT IS PLAN. I KNOW THIS SLIDE IS BUSY AND WE WILL GO THREE EACH OF THESE BOXES IN TURN, SO FOR RIGHT NOW, YOU KNOW I JUST WANT TO MAKE THE POINT THAT THE IDEA OF THE PLAIN IS TO FOCUS ON AREAS OF OPPORTUNITY THAT APPLY ACROSS THE BREDTH OF NIH RESEARCH AS WELL AS A SET OF UNDERLYING PRINCIPLES THAT UNDERLIE EVERYTHING. LET'S SEE, OKAY, SO I'LL MOVE THROUGH THEN EACH OF THESE NOW. SO THE PLAN WILL START WITH A HIGH LEVEL DESCRIPTION OF THE NIH AND BIOMEDICAL RESEARCH ENTERPRISE, DESCRIBE THE MISSION, CURRENT STATUS OF BIOMEDICAL RESEARCH AND NIH'S ROLE IN LEVERAGING UNIQUE OPPORTUNITIES. IT'LL INCLUDE DESCRIPTION OF THE CURRENT RESEARCH LANDSCAPE AND CHALLENGES BY THE COMMUNITY ESPECIALLY IN THE LOSS OF PURCHASING POWER OVER THE LAST 10 YEARS. IN ADDITION, IT WILL TOUCH ON THE CONTINUUM OF BASING APPLIED RESEARCH AND BI-DIRECTIONAL NATURE WILL HAVE A DRE SCRIPGZ OF THE EXTRAMURAL, RESEARCH AND TRAINING PROGRAMS AND WE'LL TALK ABOUT THE NIH COMMON FUND WHICH IS AN EXCELLENT EXAMPLE OF A CROSS CUTTING TEAM AND ALSO TALK AUT THE STRUCTURE AND FUNCTION OF THE DIFFERENT ICs. OKAY, SO THE MAIN PORTION OF THE PLAN WILL FOCUS ON WHAT WE'RE CALLING AREAS OF OPPORTUNITY TO APPLY ACROSS BIOMEDICINE. THESE ARE FUNDAMENTAL SCIENCE, HEALTH DISEASE PREVENTION AND TREATMENT AND CURES. SO THE ARROWS SHOW THE BI DIRECTION ATINATE EXPORT CROSS FERTILIZATION THAT HAPPENS AMONG THE -6R7 IN DIFFERENT AREAS. - IN DIFFERENT AREAS. SO FOR EACH AREA OF OPPORTUNITY THE PLAN WILL HAVE A SUCCINCT DESCRIPTION OF EMERGENT OPPORTUNITIES AND WHAT NIH NEEDS TO DO TO REALIZE THE OPPORTUNITY AS LAS HAVING EXAMPLES FOR ILLUSTRATIVE PURPOSES ONLY FOR BREAK THROUGHS THAT ARE RELEVANT TO THE AREAS. AND THIS IS WHERE WE SWITCHED OUT THE SLIDES TO HAVE THINGS MORE APPLICABLE, IN THE NINDS, AS WELL AS NIH PLAN. OKAY. SO IN TERMS EVER FUNDAMENTAL SCIENCE, FIRST AREA OF OPPORTUNITY NIH RECOGNIZES BASIC RESEARCH IS THE SCIENTIFIC PROGRESS ISSUES MEDICINE AND HEALTH AND THE DORPHY SET THE STAGE FOR FUTURE ADVANCES AND TREATMENTS AND CURES, AND SO NIH MUST MAINTAIN A INVESTMENT AND FUNDAMENTAL RESEARCH AND SCIENCE. IN TERMS OF THE SECOND BULLET, IT OFTEN UNPREDICTABLE AND INVESTMENTS OF A BROADER WAY OF RESEARCH TOPICS BECAUSE OF THIS UNPREDICTABILITY. FUNDMENTAL SCIENCE SHOULD EXPLORE NOW AND UNCHARTED AREAS WITH IMPORTANCE DEFINED BY BREDTH AND SCOPE, NOT BY TARGETED NEEDS. IN TERMS OF THE METHODS, STIMULATE PROGRESS, NIH RECOGNIZES THE IMPORTANCE OF FUNDAMENTAL SCIENCE AND MEDICINE AND ADVANCES IN CLINICAL METHOD CANS STIMULATE PROGRESS AND BASIC RESEARCH. THE DOORS BETWEEN THE LAB AND THE CLINIC MUST BE OPEN TO MAXIMIZE BI-DIRECTIONAL INTERACTIONS AND COMMUNICATION. IN TERMS OF TECHNOLOGY, EVERYONE KNOWS ADVANCES IN TECHNOLOGY WILL ACCELERATE SCIENCE. NIH SHOULD SUPPORT TECHNOLOGICAL ADVANCEMENTS AND DISSEMINATION AND IT SHOULD ALERT TO AND SUPPORT TECHNICAL OPPORTUNITIES AS THEY ARISE. AND LAST THING IN THE DATA SCIENCE, COMPUE TAGS TAGSAL SCIENCE ARE IMPORTANT IN BIOMEDICAL RESEARCH AND NIH MUST ENVISION A SCIENCE AND BIOMEDICAL RESEARCH WITH FIELDS SUCH AS COMPUTER SCIENCE, STATISTICS AND DATA SCIENCE. SO FOR THE ILLUSTRATIVE EXAMPLE WE CHOSE OPTOGENETICS. THIS IS A RESEARCH TOOL THAT WAS DISCOVERED OR PUT TOGETHER--DISCOVERED IS THE BEST WORD IN 2006 BY DR. CARL DEISSEROTH, AND IT'S A TOOL THAT ALLOWS NEURONS TO BE TURNED ON WITH PULSES OF LIGHT. IT'S QUITE REVOLUTIONARY. THERE ARE HUNDREDS OF INVESTIGATOR WHO IS ARE USING THIS TECHNIQUE TO DISSECT IF YOU WILL NEURAL CIRCUITS THAT WORK. THESE ARE THE AREAS THAT SOME OF THE EXCITING WORK'S GOING OLOOKING AT PARKINSON'S DISEASE, DEFINING HOW DEEP BRAIN STIMULATION WORKS, LOOKING AT HOW ABNORMAL ACTIVITY, LEADS TO SEIZURES AFTER STROKE. GETTING AT WHAT THE NEUROCIRCUITRY FOR FEAR MEMORIES ARE, CAN HAVE APPLICATIONS FOR THINGS LIKE PTSD, AND EXCITINGLY THE FDA APPROVED THE FIRST OF ITS KIND CLINICAL TRIAL OF OPTOGENETICS FOR DEGENERATIVE BLINDNESS. MOVING TO IN THE NEXT ONE, AREAS OF OPPORTUNITY, NIH DESIGNS IMPORTANCE OF STUDYING HEALTHY INDIVIDUALS AND PREVENTION PROGRESS OF DISEASES TTARGETS SOCIAL, PHYSICAL AND BIOLOGICAL ENVIRONMENTS AND BEHAVIOR. IN TERMS OF THE FIRST BULLET HERE, NIH RECOGNIZES IMPORTANCE OF HEALTHY INDIVIDUALS IN NORMAL PHYSIOLOGICAL FUNCTIONING, THIS IS INDIVIDUALS WHO MAINTAIN HEALTH THROUGHOUT LIFE AND THOSE WHO ARE RESILIENT TO DISEASE DESPITE THE PRESENCE OF CHRONIC CONDITIONS AND OTHER RISK FACTORS. NIH BELIEVES THERE'S VALUE IN INVESTIGATING BOTH HEALTHY AND EFFECTIVE POPULATIONS FOR DETERMINING THE COST OF DISEASE. NIH FOCUSES ON THE NEED FOR EARLY DETECTION AS A WAY TO BETTER UNDERSTAND DISEASE, ONSET AND FACILITATE EARLY INTERVENTIONS AND LAST ONE DOWN HERE IN TERMS OF HEALTH DISPARITIES, NIH APPRECIATES THE NEED TO ELIMINATE THESE USING ADMIN SPACE INTERVENTION RESEARCH. IT'S FOR NOT ONLY HEALTH IN GENERAL BUT HEALTH EQUITY AS WELL. SOCIAL DETERMINANTS OR ASPECT OF UNDING AND THE DISPORTIONATE DISEASE RISK IN CERTAIN POPULATIONS. SO FOR THE ILLUSTRATIVE EXAMPLE THAT WE CHOSE FOR THIS IN TERMS OF DISEASE PREVENTION IS, THIS PROJECT THAT'S ACTUALLY BEING SUPPORTED BY A NUMBER OF INSTITUTES, LOOKING AT THE ISSUE OF HIGH BLOOD PRESSURE AND THE MOST EFFECTIVE WAY OF KEEPING IT UNDER CONTROL. SO I'M SURE AS EVERYONE KNOWS HIGH BLOOD PRESSURE IS LEADING CARDIOVASCULAR DISEASE AND ALSO REAGE RELATED DEMENTIA, THIS IS A TRIAL FOR A STUDY LOOKING AT BLOOD PRESSURE BELOW CURRENT GUIDELINES WHICH ARE 140-MILLIMETERS OF MERCURY, TOBLY 120, THAT WILL REDUCE RATE OF HEART DISEASE, STROKE AND KIDNEY DISEASE, AND THEN THE ADD ONS, MEMORY AND COGNITION AND DECREASE HYPERTENSION IS TESTING LOWER DOSE EFFECTS ON DEMENTIA AND COGNITIVE DECLINE AND BRAIN PATHOLOGY. SO AS BENEFITS, A CONDITION THAT EFFECT A NUMBER OF DIFFERENT ORGAN SYSTEMS, AS A MENTION THERE'S A NUMBER OF ICs THAT ARE INVOLVED NHLBI, NIDDK, AND NIA, AND SO OVER ALL HOPEFULLY THESE PROJECTS WILL PROVIDE QUICKLY NEEDED EVIDENCE REGARDING BENEFITS, RISK AND FEASIBILITY HAVING LOWER BLOOD PRESSURE. TIGHTER BLOOD PRESSURE CONTROL. OKAY, THE LAST AREA OF OPPORTUNITY IS TREATMENTS AND CURES. SO IN GENERAL, CLINICAL RESEARCH OF COURSE REQUIRES TESTING THE MOST PROMISING THERAPY, EFFORTS OF TRANSLATIONAL INVESTIGATORS TO PROVIDE THE FOUNDATION FOR DISCOVERING NEW TREATMENTS. PROGRESS IN MEDICINE REQUIRES ADVANCES IN CLINICAL RESEARCH TOOLS AND METHODS MUST, VOLVE TO ALLOW FOR SCIENTIFIC FLEXIBILITY AND PROMOTE BETTER OUTCOMES. IN TERMS OF MOLECULAR KNOWLEDGE, THE OPPORTUNITIES TO DISCOVER NUTRIENTS AND CURES ON THE KNOWLEDGE ARE TREMENDOUS AND GETTING BETTER EVERY DAY. NIH IS COMMITTED TO MECHANISMS ON A CELLULAR DISEASE AS THIS HAS A POTENTIAL LEAD TO NEW THERAPEUTIC INTERVENTIONS. OF COURSE ORGANS AND DISEASES ARE NOT FOUND FOR ISOLATION, BUT RATHER AS PARTS OF A SYSTEM, SO THERE'S BEEN A BENEFIT IN LOOKING AT THINGS FROM A SYSTEM CONTEXT RATHER THAN LOOKING AT SINGLE ISSUES OR ORGANS. NIH RECOGNIZES IN TERMS OF PARTNERSHIPS THAT BREAKTHROUGHS NEED PARTNERSHIPS AND OFTEN COME FROM UNEXPECTED DIRECTIONS. SO NIH WILL STRIVE TO ACHIEVE A BRAD PORTFOLIO, TO APPLIED SCIENCE FOR IMPACT AND MULTIPLE DISEASES AND CONDITIONS AND WILL LOOK FOR TO ENGAGE OTHER GROUPS BOTH INSIDE AND OUTSIDE GOVERNMENT TO ADVANCE ITS MISSION. SO THE FINAL PART OF THE PLAN--OOPS, I FORGOT THE EXAMPLE, SO THIS CELLS GENERATED FROM PATIENTS WITH NEUROLOGICAL DISORDERS. THERE WAS A LOT OF RAPID ADVANCEMENT IN THIS TECHNOLOGY FOR 2006 TO 2009: IN 2009 WITH ARRA FUNDING WE FUNDED A CONSORTIUM TO DEVELOP CELL LINES AND NOW ALLOW THESE LINES IN A REPOSITORY MAINTAINED THROUGH COOPERATIVE AGREEMENTS AND ARE FREELYY AVAILABLE TO INVESTIGATORS FOR RESEARCH. SOME OF THE DIFFERENT TYPES OF DISEASES ARE IN THIS REPOSITORY. I'M SORRY, SOME OF THE SPECIFIC DISEASE CELL LINES ARE IN THIS REPOSITORY INCLUDE PARKINSON'S HUNTINGTON'S ALS AND OTHER DISEASES, ALZHEIMERS DEMENTIA AND DYSTONIA. SO GETTING BACK TO THE THEME OF THE AREA OF OPPORTUNITY, THESE CELLS ALLOW INVESTIGATORS TO STUDY THE MOLECULAR AND CELLULAR DISEASE WITH THE GOALS AND TREATMENTS BASED ON THIS KNOWLEDGE. OKAY, SO FINAL PART OF THE PLAN IS UNIFYING PRINCIPLES. AND THEY INCLUDE TWO OF THEM HERE, SETTING PRIORITIES AND ENHANCING STEWARDSHIPS MPLET THESE SHOULD HELP GID NIH IN THE MOST EFFECT I WAY POSSIBLE AND ARE CRIT AT ACHIEVING AREAS OF OPPORTUNITY. AGAIN FOR EACH OF THESE THERE WILL BE DISKRIMS OF THE CURRENT STATUS AND HOW THEY WILL GET AT THE OPPORTUNITIES AS WELL AS SPECIFIC EXAMPLES. SO IN TERMS OF SETTING PRIORITIES FIRST ONE, NIH CONSIDERS SEVERAL FACTORS IN DETERMINING PRIORITIES. IN ORDER TO REDUCE ILLNESS AND DISABILITY ASK HAVE THE LARGEST IMPACT POSSIBLE, NIH CONSIDERS DISEASE BURDEN TO BE AN IMPORTANT FACTOR, HOWEVER NOT THE ONLY FACTOR BUT ONE OF SEVERAL. NIH ALSO VALUES SCIENTIFIC OPPORTUNITY WHICH CAN ARISE FROM ANYWHERE AND RELATE TO ANY GROUP OF DISEASES. NIH AS A WHOLE MUST STRIVE TO BE AS FLEXIBILITY AS POSSIBLE BECAUSE PRIORITIES CAN BE SHIFTED AS NEEDED. IN TERMS OF THE THIRD BULLET HERE, RARE DISEASES ARE A PRIORITY AS WELL. SCIENTIFIC ADVANCES THAT LEAD TO TREATMENTS OR CURES FOR DISEASES, EVEN WHEN IT IS SIZE OF THE IMPACTED POPULATION IS SMALL, ARE NO LESS VALUABLE IN EFFORTS TO IMPROVE HEALTH. AND NIH IS A LEADER IN THIS AREA. AND THEN LASTLY, NIH ALSO CONSIDERS THE VALUE PERMANENTLY ENDING A PANDEMIC OR ERADIATEICATING A DISEASE AS A PRIORITY. FOR THE ILLUSTRATIVE EXAMPLE WE'VE CHOSEN HERE, WHAT WE'VE CHOSEN IS RARE DISEASES, SO I PUT THIS SLIDE ON PURPOSE SO THAT THE COLOR MAY BE--IF YOU NODDING OFF, YOU WOULD GET JOLTED BACK AWAY. SO THIS IS THE RARE DISEASE CLINICAL RESEARCH NETWORK. IT'S RUN BY NCATS, THE NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCE IN COLLABORATION WITH 10 OTHER ICs, INCLUDING NINDS. IT WAS ESTABLISH INDEED 2003; IT'S PURPOSE IS TO FACILITATE RESEARCH FOR MULTISITE CONSORTIA ON THREE RELATED DISEASES AND THEY STUDY THINGS LIKE NATURAL HISTORY, CLINICAL TRIALS, DEVELOPING UNIFORM PROTOCOLS AND CENTRALIZED DATA REPOSITORIES. IMPORTANTLY, THESE ARE THE CONSORTIA COLLABORATES WITH THE NONPROFIT GROUPS AS RESEARCH PARTNERS AND I THINK ON THE SLIDE, THEY LABEL THEM PATIENT ADVOCACY, P A G BUT THE SAME THING IS NONPROFITS. CURRENTLY, THERE ARE 22 DISTINCT CONSORTIUM AND THE ONES THAT ARE NEUROSCIENCE RELATED, THAT WE HAVE INVOLVEMENT IN, ARE THE ONES IN ORANGE, SO CAN YOU SEE THAT 14 OF THE 22 ARE NEUROSCIENCE RELATED. SO I THINK WE'VE REALLY AS AN INSTITUTE TAKEN ADVANTAGE IN PROGRAM DIRECTORS, HAVE TAKEN ADVANTAGE OF THE SET UP TO DRIVE PROGRESS AND A LOT OF THESE RARE DISORDERS. OKAY, THE LAST UNIFYING PRINCIPLE IS ENHANCING STEWARDSHIP. SO TO ACCOMPLISH THIS MISSION, NIH STRIVES TO PROMOTE THE HIGHEST LEVEL OF PUBLIC ACCOUNTABILITY AND SOCIAL RESPONSIBILITY IN THE CONDUCT OF MEDICINE. IT'S A CRITICAL PIECE OF A STRATEGIC PLAN AND TELL CONTINUE TO PURSUE MULTIPLE AVENUES TO ADDRESS THIS. THE FIRST BULLET HAS TO DO WITH TRAINING, NIH WILL CONTINUE TO RECRUIT, AND RETAIN OUTSTANDING BIOMEDICAL RESEARCH, BY ENHANCING THE DEVELOPMENT OF YOUNG SCIENTISTS EMPLOY SECONDLY, NIH STRONGLY BELIEVES THE KEY TO PRODUCING SCIENTIFIC IDEAS AND DISCOVERIES AND THERE ARE A NUMBER OF ACTIVITIES ALREADY UNDERWAY ACROSS NIH TO WORK ON THIS ISSUE. NIH WILL STRIVE TO ENCOURAGE INNOVATIVE RESEARCH WITH THIS NEW, UNIQUE AND MOVE THE FIELD FORWARD. NIH WILL INNOVATION AND SPORTING INDIVIDUAL INVESTIGATORS WITH THE IDEA THAT SPANS OR DISCIPLINES AND PARTICULARLY CREATIVE IN A POTENTIAL FOR HIGH IMPACT. NOW NIH APPRECIATES IN TERMS OF THIRD BULLET HERE, OR FOURTH BULLET, NIH APPRECIATES THE AFFLU ID OF RESEARCH AND ONE WAY TO REFLECT THESE IN THE NIH PORTFOLIO IS BY REVIEWING AND OPTIMIZING THE PROCESS FOR MAKING FUNDING DECISIONS. THE NEXT BULLET IN TERMS OF PARTNERSHIPS AS WE SAID BEFORE, PARTNERSHIPS ARE AN INVALUABLE WAY FOR DISEASE BARRIERS AND NIH SCIENCE AND NIH WILL CONTINUE TO PURSUE THESE COLLABORATIONS ACTIVELY. THE NEXT BULLET ARE IMPORTANT ISSUES ALONG WITH MANY OTHERS TO ADDRESS THESE ISSUES AND PROMOTING DATA SHAIRG WHICH CAN BE A KEY COMPONENT. OF ANY EFFORT OF TRANSPARENCY AND ACCOUNTABILITY. AND REDUCE ADMINISTRATIVE BURDEN, AND STRIVES TO REDUCE THE ADMINISTRATIVE BURDEN AND MAINTAINING TRANSPARENCY SO WE CAN BE AS EFFICIENT AS POSSIBLE IN TERMS OF THE USE OF OUR FOUNDS. AND THE LAST IS EMPLOYING RISK MANAGEMENT STRATEGIES. AS A STEWARD OF PUBLIC FUNDS NIH IS RESPONSIBLE FOR MAINTAINING MANAGEMENT IT SYSTEMS AND WILL UTILIZE TO IDENTIFY, ANALYZE AND MANAGE AND MITIGATE RISKS. FOR THE ILLUSTRATIVE EXAMPLES I WANT TO USE, THERE'S BEEN A LOT GOING ON AND YOU KNOW NINDS HAS REALLY BEEN THE LEADER IN THIS FIELD ONE OF OUR DIRECTORS, WAS ONE OF THE FIRST IN THE INSTITUTE TO BRING THIS UP AS AN IMPORTANT ISSUE THAT WE SHOULD BE PAYING ATTENTION TO. STARTED TALKING TO OTHER INSTITUTES, TO THE JOURNAL EDITORS AND OTHERS IN THE AREA CULMINATING IN THIS HIGH PROFILE WORKSHOP, IN 2012, THAT LED TO A NATURE PAPER, CAN YOU SEE A LOT OF PEOPLE WITH DR. STORY LANDIS, OUR FORMER DIRECTOR, NOW A NUMBER OF JOURNAL EDITORS EMBRACE THIS CALL, NIH IS DOING A LOT IN THIS AREA, HERE'S A COUPLE EXAMPLES, AND DR. COLLINS AND DR. TABAK, I THINK THIS WAS A COMMENT IN SCIENCE ON THIS; THIS IS SOMETHING THAT'S VERY ACTIVE AND AGAIN, THIS IS I THINK AN AREA WHERE NINDS HAS TAKEN THE LEAD. SO IN SUMMARY THE OVERALL GOALS ARE LAID OUT TO ACHIEVE THEM, EACH IC HAS ITS OWN INDIVIDUAL PLAN. SO THIS SLIDE IS A TIMELINE FOR THE DEVELOPMENT OF THE PLAN. I WILL NOT WALK THROUGH EACH STEP, I JUST WANT TO DRAW YOUR ATTENTION TO THE RED BOX THAT,'S WHERE WE ARE NOW, WHERE THERE'S FEEDBACK GOTTEN AT THE DIFFERENT ADVISORY COUNCILS AND AT MEETINGS LIKE. THIS THERE'S GOING TO BE SEVERAL ACISIONAL STEPS, BRIEFING HHS, INCORPORATING ALL THE FEEDBACK THAT NIH RECEIVED FROM ALL THE DIFFERENT SOURCES OF INPUT, FROM BRIEFING KEY HILL STAFFERS, AND THEN THE ADVICE DIRECTOR WILL WEIGH IN AGAIN AND AS WALTER MENTIONED IT NEEDS TO BE TURNED INTO THE CONGRESS BY THE MIDDLE OF DECEMBER. SOPHISTICATED THAT'S IT FOR THE PRESENTATION. NIH HAD--THESE ARE QUESTIONS THAT NIH WAS INTERESTED IN GETTING FEEDBACK ON, WHAT ARE THE BENEFITS AND DRAWBACKS OF THE FRAMEWORK. NIH COMPATIBLE WITH THE BROAD SCOPE OF THE NIH MISSION, ARE THERE ANY TRANS-NIH THEMES THAT HAVE NOT BEEN CAPTURED AND ARE THERE FUTURE ENTITIES THAT? SO WE COULD DISCUSS, GET ANYBODY'S FEEDBACK ON ANY OF THESE QUESTIONS. WALTER AND I CAN TRY OUR BEST TO ANSWER QUESTIONS YOU MAY HAVE ABOUT THE PLAN. WE HAVE ANOTHER SET OF QUESTIONS THAT ARE SET UP FOR THE DISCUSSION SESSION SO MAYBE I'LL PUT THOSE UP TO GET PEOPLE THINKING BUT I'M OPEN TO QUESTIONS ON ARE COMMENTS ABOUT THE PLAN OR ANSWERS, FEEDBACK ON ANY OF THESE QUESTIONS. >> SO I GUESS THE BIG QUESTION OUT THERE IS WHAT WOULD BE--WHAT IS THE CONSEQUENCE OF THE PLAN. SO, YOU KNOW ONE SCENARIO, THEY PT A PLAN IN AND THEN, PEOPLE GO THROUGH THE PLAN, STEP-BY-STEP AND EVERY YEAR THEY SAY WHAT DO YOU DO HERE, WHAT DID YOU DO THERE? AND THAT WOULD HAVE MAJOR CONSEQUENCE. THE OTHER ONE THAT WOULD BE, YOU KNOW A GENERAL GIDDING PRINCIPLE TYPE PLAN WHICH HAS VERY LITTLE TEETH TO IT. AND HAS, YOU KNOW NOT MUCH CHANGE IN HOW NIH OPERATES, I GUESS, SO THAT WILL BE THE TWO OULD PLAY OUT. ENDS OF THE SPECTRUM ON HOW THIS SO I THINK WHAT GOES IN IS POTENTIALLY IMPORTANT DEPENDING ON HOW IT'S USED, CERTAINLY IN THE FIRST CASE SCENARIO, IT'S IMPORTANT IF THE PLAN IS USED AS KIND OF A BIBLE OF WHAT NIH SHOULD BE DOING. THEN YOU REALLY WANT TO BE INCREDIBLY CAREFUL AND SO, I THINK--THE FIRST QUESTION I G'S FROM WHAT PEOPLE HEARD, WHAT'S MISSING. SO WE DIDN'T HEAR A LOT IN THE PLAN ABOUT HOW NIH SHOULD INTERACT WITH PATIENTS OR PATIENT GROUPS, RIGHT? >> RIGHT. BEYOND SAYING THAT SHOULD BE A PRIORITY AND THEN NIH LOOKS FOR MORE PRIORITIES TO DO THAT. RIGHT. I THINK THAT SOMETHING COULD BE EMPHASIZED MORE. ANYBODY ELSE HAVE ANY KIND OF--I MEAN WHAT'S YOUR FIRST TAKE ABOUT WHAT YOU SEE? I MEAN EVERYBODY HAS A DIFFERENT OPINION WHEN THEY SEE THIS THE FIRST TIME. >> WELL FIRST THING I WAS WONDERING IS OW LONG TELL BE? EVEN THE LARGEST CORPORATION IN AMERICA HAVE TO HAVE SHORT STRATEGIC PLAN. >> SO THEY SAID IT'S NOT GOING TO BE MORE THAN 15 PAGES. >> WOW. >> RIGHT. IF I WROTE OUT EVERYTHING I JUST SAID, WOULD BE 15 PAGES. SO I'M NOT SURE HOW THEY'RE GOING TO-- >> THE OTHER THING WOULD BE THIS YEAR'S TRENDS BUT DANGEROUS SOMETIMES TO GET--MAKE TOO BIG OF YOUR STRATEGIC STORY, WHAT'S HOT THIS YEAR, IPS CELLS OR ONCA GENETICS WHATEVER THE THING IS THIS YEAR BUT THE OTHER THING IS-- >> LET ME CLARIFY, THOSE ARE EXAMPLES I USED, I DON'T KNOW WHAT THEY WILL HAVE IN THE PLAN. THOSE ARE EXAMPL- >> WHERE THE SHIFT ARE LOOKING AT REALLY LARGE DATA SETS, AND HUGE POPULATIONS, THAT IS THE BIG SHIFT, SO, IS IT DOES FEEL STRATEGIC, I GUESS THE ONLY OTHER THING IS, COMPANIES HAVE RUN THE BIG PART OF STRATEGY IS KNOWING WHAT YOU'RE NOT GOING TO DO, SO YOU PROBABLY WORTH WHILE TO NOT ASK PEOPLE WHAT THE STRATEGEY SHOULD BE FEELING BUT WHAT WE THINK, WHEN WE'VE THOUGHT THAT MAYBE THIS SHOULD BE THE NIH'S GAIN. SO IT'S--JUST THROW OUT CONTROVERSIAL EXAMPLES, I'LL SAY, WHEN FRANCIS AND OTHERS WANTED TO DO--HAVE CHEMICAL LIBRARIES AND GET INTO--CLOSER TO THE DRUG INDUSTRY'S ROLE, THERE'S BEEN CONTROVERSYY ABOUT THAT AND YOU KNOW HOW MUCH--THERE'S ALWAYS THE ONGOING DEBATE ABOUT HOW MUCH BASIC SCIENCE VERSES TRANSLATIONAL. SO THAT EXERCISE IS SAYING WELL, LET'S TALK ABOUT THE WHAT THE NIH SHOULD DO, IT WILL BE HELPFUL AND THE ONLY OTHER THING I WILL THROW OUT BECAUSE I WANT TO KEEP IT COLORFUL OUT HERE, THE SAME QUESTION I ASK BEFORE TO NIH PEOPLE OVER DRINKS AND THAT IS IF YOU HAD 30 BILLION DOLLARS A YEAR PROMISED TO YOU BUT THE NIH DIDN'T EXIST, RIGHT? HOW WOULD YOU DESIGN THE NIH TODAY, KNOW WAG YOU KNOW AND YOU PUT A BUNCH OF PEOPLE TOGETHER WHO REALLY KNOW WHAT'S NEEDED TO FIGURE THAT OUT AND YOU HAVE THIS AMAZING NEW PLAN FOR AN ENTITY. AND YOU SAY HOW DOES THAT COMPARE WITH WHAT WE HAVE, WHICH IS OBVIOUSLY DIFFERENT. AND THEN NORMALLY OVER THE NEXT 10 YEARS OR FIVE YEARS HOW WE WILL GET TO WHAT WE HAVE TO WHAT WE THINK WE OUTTO HAVE AND I DON'T FEEL LIKE YOU REALIZE THERE ARE SOME THINGS THAT CAN NEVER DO THAT AND THAT'S WHERE AN NIH DIRECTOR CAN DO A UNIQUE CONCEPT, MY ONLY CONCERN WITH STRAY JECTORY TEENINGIC PLANNING IS PEOPLE DON'T THINK THE BOX ENOUGH SO THAT WOULD BE MY OTHER CONTEST SUGGESTION. >> I HAVE A COUPLE OF COMMENTS THAT ARE NOT ABOUT SO MUCH THINGS THAT ARE LEFT OUT OR NOT CAPTURED AS IN THE THIRD BULLET THERE BUT POINTS OF EMPHASIZE ABOUT TRANSNIH THEMES, BASICALLY. I THINK THE TRANSNIH THEMES SHOULD BE A REAL CENTERPIECE FOR THE STRATEGIC PLAN BECAUSE WE ALL KNOW THERE ARE 22-ODD INSTITUTES AND OFFICES AND SO MUCH INTEREST IN CONGRESS AND THROUGHOUT THE COMMUNITY. IN MAKING THOSE 22 CENTERS INTO A NATIONAL INSTITUTE OF HEALTH THAT'S COLLABORATIVE, FULLY ACROSS NIH WIDE THEMES. AND YOU KNOW, NINDS IS PROBABLY IN THE GIFTED POSITION TO DRIVE THAT POINT HOME BECAUSE OF THE NEUROSCIENCE CONSORTIUM AMONG INSTITUTES. A WE'VE GOT COLLABORATIONS AMONG THIS AND THINGS LIKE MIGHT O CHOND RIIAL FUNCTION AND DYSFUNCTION, AND SO MANY OF OUR DISEASES CUT ACROSS INSTITUTE LINES SO WE WANT TO HEAR MORE AND MORE ABOUT HOW THE INSTITUTES WILL WORK TOGETHER IN TAKEN--THEY REGARD AND IT WAS MENTIONED EARLIER, HOW TO WORK WITH ALL THE STAKEHOLDERS IN THAT REGARD. ACROSS THE NIH INSTITUTES, STAKEHOLDERS LIKE PATIENT GROUPS THAT ARE HERE TODAY, STAKEHOLDERS LIKE INDUSTRY THAT ALSO WELL REPRESENTED HERE TODAY. THE OTHER--OTHER POINT ABOUT TRANSNIH, INSTITUTIONAL COLLABORATION IS YOU LOOK AT THE TRANSLATIONAL OFFICES AND THE CLINICAL OFFICES HERE AT NINDS, AND ALMOST EVERY ONE OF THE OTHER INSTITUTES AND WE'VE GOT THIS NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES THAT'S ALL ABOUT TRANSLATION AND CLINIC. AND I DON'T SEE ENOUGH COLLABORATION AMONG ALL THE INSTITUTES WITH NCATS TO DRIVE THAT TRANSLATIONAL AND CLINICAL THEME AND EFFORT. THERE ARE MECHANISMS IN PLACE LIKE THE CTSAs, 62 SITES AROUND THE COUNTRY, THEY'RE NOT EVEN SUFFICIENTLY COLLABORATIVE. THEY'RE SUPPOSED TO BE A NETWORK BY CONGRESS AND THEY'RE 62 COMPETING CTSA SITES FOR BIG BUDGETS. IT'S THE LARGEST SINGLE NIH BUDGET ITEM THAT EXISTS IN ANY INSTITUTE. AND WE'VE GOT HERE AT NINDS, THE NEXT NEURONETWORK, 25, DIFFERENT LOGICAL TRANSLATION AND SITES AND NEUROLOGICAL FOR CLINICAL TRIAL. 23 OF THEM ARE CTSA SITES. SO, WE NEED MORE AND MORE COLLABORATION AMONG THE INSTITUTES AND WITH--BETWEEN THE INSTITUTES AND NCATS IN BOTH TRANSLATION AND CLINICAL. >> WORKING AT A PRIVATE COMPANY CHARGED WITH TRANSLATING RARE DISEASE PHASES, TWO THINGS I WOULD LIKE TO HIGHLIGHT. ONE IS I PREESED TO RECEIVE THE NEW FOCUS ON DRIVING ACADEMIC RESEARCHERS TOWARDS A MORE ROBUST DATA SET SO THAT MORE OPPORTUNITIES CAN BE TRANSLATED FROM THE ACADEMIC SETTING INTO INDUSTRY AND FORWARD. I TALKED A LOT OF ACADEMICS THAT SAY WE'RE NOT INCENTIVIZED TO GO AND DO THINGS LIKE RUN REPRODUCIBLE EXPERINTS WHERE WE'VE DONE THE SAME EXPERIMENT OR DOSE RESPONSES OR SO FORTH, THOSE ARE THINGS THAT THE NIH COULD TURNOVER CERTAINLY DRIVE THROUGH FUNDING MECHANISMS. THE SECOND IS I SEE A VARIETY OF OPPORTUNITIES WHERE THE WERE IS GOING ON AND WHERE FROM THE STANDPOINT OF EITHER A COMPLEX PATIENT POPULATION OR VERY SMALL PATIENT POPULATION, THESE ARE EXCITING THERAPIES THAT WILL FALL THROUGH THE CRACKS, WE WILL FALL BELOW, EVEN SMALL BIOTECH COMPANIES, TO GO LIKE OURSELVES TO DRIVE FORWARD AND I THINK THE NIH NEEDS TO FIND A MECHANISM BY WHICH THE SMALLER OPPORTUNITIES WHERE PATIENT CANS SEE THERAPIES ARE ON THE CUSP OF MOVING INTO THE CLINIC CAN HELP CARRY THOSE FORWARD AND PERHAPS DRIVE THEM ALL THE WAY THROUGH, THROUGH SOME FASHION TO THE POINT WHERE THEY CAN BE DELIVERED ON A RIGOROUS REPRODUCIBLE BASIS TO THE PATIENTS BECAUSE I THINK FOR MANY OF THESE SMALLER DISEASE INDICATION, COMPANIES ARE NOT GOING TO BE ABLE TO DO THAT. >> SO I'D LIKE TO MAKE TWO COMMENTS, THE FIRST IS ABOUT PHYSICS, SO THE LAST TIME I LOOKED, NO ONE IN THEIR LABORATORY AT MIT OR HARVARD OR STANFORD OR SO ON WAS LOOKING FOR THE HIGS BO SUN IT WAS AN ACTIVITY THAT LEADS TO 500 AUTHORED PAPERS LOOKING FOR THE HIGS BOSUN, I DIDN'T KNOW IT WAS LOST PERSONALLY BUT THE POINT IS, AT WHAT POINT DO WE TRANSITION MEDICAL SCIENCE TO THE LEVEL WHICH IS MUCH MORE LARGE GROUP, NOT JUST BIG DATA BUT LARGE GROUP WORKING ON VERY IMPORTANT PROBLEMS. THERE ARE PLENTY OF VERY IMPORTANT PROBLEMS AND SO I JUST LIKE TO REENFORCE THE COLLABORATIVE ASPECTS AS ONE OF THE REALLY IMPORTANT THINGS THAT NEEDS TO BE IN THE STRATEGIC PLAN, BUT THE QUESTION IS, AT WHAT POINT IN THE FUTURE DO WE TRANSITION TO BE MUCH MORE LIKE PHYSICS, PHYSIC SYSTEM PROBABLY A HUNDRED YEARS AHEAD OF MEDICAL SCIENCE, BUT AT WHAT POINT DO WE TRANSITION AND AT WHAT POINT ARE THERE 500 PERSON TEAMS WORKING ON THE SINGLE PROBLEM SOMEWHERE IN SOME INSTITUTE, DOESN'T NEED A PARTICLE ACCELERATOR BUT THE CONCEPT IS THERE. THE NEXT THEME IS A SIMILAR THEME AND IT'S AN INTERESTING THING I'VE LEARNED HAVING COME OUT OF COMPANIES AND ACADEMIC RESEARCH AND PATIENT ADVOCACY OIONS AND THAT IS THAT EACH OF THE PEOPLE IN THIS ROOM ARE HERE BECAUSE THEY CARE ABOUT THEIR DISEASE OF INTEREST. AND THAT'S GREAT BECAUSE IT PUSHES FORWARD THEIR DISEASE OF INTEREST, BUT YOU KNOW THIS STUDYING MY DISEASE OF INTEREST VERSES HEALTHY CONTROLS IS NOT NECESSARILY A WAY TO FIND OUT THE KEY INFORMATION ABOUT YOUR DISEASE OF INTEREST VERSES SICK PERSON. AND I THINK MORE OF THE WORK THAT BRINGS DIFFERENT DISEASE GROUPS AND THEIR RESOURCES, LIKE BIOBANKS, ET CETERA, ET CETERA, TOGETHER UNDER AN UMBRELLA WHERE THEY CAN DO THE COLLABORATIVE WORK AND THE DIFFERENTIAL DIAGNOSTIC WORK IF YOU LIKE, THAT IS SO IMPORTANT. AND THIS IS PARTICULARLY TRUE OF THE AUTOIMMUNE DISEASES LIKE MULTIPLE SCLEROSIS AND RHEUMATOID ARTHRITIS, ET CETERA. BUT IT'S JUST ACROSS ALL DISEASES. SO HOW MANY WAYS CAN A NEURON DIE? AND HOW MANY PEOPLE ARE INTERESTED IN THAT IN THIS ROOM, BUT ARE MORE INTERESTED IN A SINGLE DISORDER. SO WITH REGARD TO THIS COLLABORATION, I THINK THERE'S AN ADAGE THAT SAYS, YOU BECOME CONSERVATIVE WHEN YOU HAVE SOMETHING TO CONSERVE AND I REALLY THINK THAT WE ARE--WE ARE HEADING TOWARDS A TIME WHERE THE TYPE OF RESEARCH SPONSORED BY THE NIH WILL BE MUCH MORE LIKE THE TYPE OF RESEARCH SPONSORED BY NSF AND MAJOR FUNDING ORGANIZATIONS AROUND THE WORLD. >> HI, SPEAKING AS SOMEONE WHO'S BEEN WITH THE FEDERAL GOVERNMENT FOR 44 YEARS AND WROTE MANY STRATEGIC PLANS AND WITH GAO OF EVALUATING GOVERNMENT STRATEGIC PLANS, SO I COME WITH A VERY CRITICAL BUILT IN CRITICAL ATTITUDE AND ALSO A CONGRESSIONAL PERSPECTIVE AND I APPRECIATE THAT YOU HAVE TOW HAVE OVERRIDING THEMES AND NOT GO INSTITUTE BY INSTITUTE OR ANYTHING TOO TOPICAL, BUT I HAVE TO SAY IT CAME ACROSS VERY DRY AND IT DIDN'T REALLY COME TO LIFE, EITHER, THE ORBED LYING THEMES OR--UNDERLYING THEMES OR ORGANIZING OR OPPORTUNITIES, IT JUST DIDN'T COME TO LIFE AND I GUESS, I HAVE BEEN TRACKING THE CURES ACT AND FROM OUR PERSPECTIVE, ONE OF THE POTENTIAL NEW MANDATES IS THAT FOCUS ON RARE AND CHILDHOOD DISORDERS, AND YOU KNOW THIS IS--AS RARE IS MENTIONED HERE AND PEDIATRIC IS MENTIONED HERE BUT IT NEVER COMES TO LIFE. BUT IF I WAS SOMEONE IN CONGRESS WHO CARED ABOUT THAT, I WOULDN'T KNOW YOU HAD THAT AS AN EXAMPLES CONCERN, OR A FOCUS FOR THE FUTURE. SO, IT'S JUST, YOU KNOW I'M NEW TO THIS AREA SO I'M PERHAPS NAIVE IN CRITICIZING THE OPPORTUNITY CATEGORIES, BUT FOR ME, THEY--AS SOMEONE WHO LOOKED AT THESE PLANS AND TALKED WITH CONGRESS AND MOSTLY STAFF ABOUT THESE, IT JUST DIDN'T COME ALIVE AS THE DIFFERENCE THAT NIH MAKES THE IMPACT THAT IT HAS AND WITH YOUR POINT ABOUT HOW IT'S USED, I WOULD ASSUME THAT IT WILL BE USED. EVEN IF YOU ARE MANDATED TO REPORT, THIS WILL BE THE FOCUS OF YOUR CONGRESSIONAL HEARINGS, THAT'S WHAT THESE PLANS ARE ALL ABOUT. IT'S HAVING SOME ACCOUNTABILITY OF WHAT YOU'RE SETTING OUT TO DO, AND WHAT YOU'RE ACTUALLY ABLE TO DO. SO, JUST, SOME RELEVANT PERSPECTIVE BUT ALSO LIMIT-- >> RIGHT, SO THOSE ARE GOOD POINTS WE CAN TAKE BACK TO NIH, THIS IS THE JUST THE FRAMEWORK AND I THINK THE FINAL PLAN WILL HOPEFULLY FLESH OUT AND MAKE INSPIRING THE ACTUAL LANGUAGE IN THE PLAN. BUT WE CAN MAKE--WE CAN TAKE THAT BACK TO THEM, THAT YOU KNOW THAT NEEDS TO BE AN IMPORTANT THING AND IT NEEDS TO SPEAK TO SOME OF THESE AREAS, YEAH. >> I JUST WANT TO ECHO THE THEMES FOR THE TRANSLATIONAL WORK, IN THE FINAL DOCUMENT AND IN TERMS OF LOOKING FOR TRANSNIH THEMES MAYBE TO DR. CORTET'S COMMENTS, MAYBE LOOKING AT THE OPPORTUNITY TO WORK ACROSS INSTITUTES IN ADDITION TO SPECIFIC THINGS WOULD BE HELPFUL AND THEN ONE EXAMPLE I WANTED TO BRING UP, THAT I THINK IS WORTH LOOKING INTO AS YOU'RE GOING THROUGH THIS PROCESS IS THE MUSCULAR DYSTROPHY COORDINATING COMMITTEE HAS BEEN SUCCESSFUL ESTABLISHED BY THE M. D. CARE ACT HAS BEEN IN PLACE FOR A WHILE NOW AND HAS BEEN VERY SUCCESSFUL AND HAS YIELDED GREAT RESULTS AND I THINKOOSE A GOOD EXAMPLE OF THAT WORKING REALLY WELL. >> MARRIAN BOWMAN, AND I AGREE WITH COMMENTS MADE ABOUT THE PLAN ITSELF BUT ONCE--ONCE THE PLAN IS FLUSHED OUT AND ACCEPTED, MY QUESTION IS, THEN, WHO ARE A HUGE NUMBER OF ISSUES IN HERE, HOW THEN ARE THE DECISIONS MADE ABOUT WHERE THE PRIORITIES ARE, WHERE THE FUNDS GWHAT'S THE PROCESS AFTER THAT. >> SO I THINK I HEARD DR. TABAK ASK THIS QUESTION ON THE WEBINAR AND BASICALLY HIS ANSWER WAS WE'RE PUTTING THE PLAN TOGETHER, HAVEN'T GOTTEN TO THAT PART YET. I THINK HE'S MENTIONED THAT JUST IN COMING UP WITH THESE EMERGING OPPORTUNITIES AND THE FRAMEWORK, A LOT OF DISCUSSIONS, IC DIRECTOR VS BEEN HAVING SRO BEEN POINTED TO THINGS THAT NIH COULD START DOING BUT IT HASN'T GOTTEN MUCH MORE SPECIFIC THAN THAT. BUT PERHAPS IN THE FINAL PLAN TELL BE MORE SPECIFIC BUT THAT'S SOMETHING THAT NIH WILL NEED TO ADDRESS AND I IMAGINE THOSE WILL BE A LOT OF QUESTIONS THAT WILL BE COMING UP FROM CONGRESS FROM THE DEPARTMENT IN TERMS OF ONCE THE PLAN IS OUT AND HOW IS NIH DOING THAT. AND IS SOMEONE ELSE SET UP SHOULD WE HAVE TO REPORT THAT TO CONGRESS. >> DIANE BRODENCAMP, I WANT TO FOLLOW UP, ARE THERE GOING TO BE RIPPLE EFFECTS IN REFERENCES THE INDIVIDUAL INSTITUTE'S PLAN BUT WILL THERE BE INDICATION TO TRY TO MATCH THE OVERALL STRATEGIC PLAN IN THE FUTURE? >> WHAT THEY SIDES THEY DO NOT INTEND FOR THIS PLAN TO OVERRIDE OR IMPOSE ANYTHING ON THE ICs PLANS, AGAIN BECAUSE THE IC'S PLANS ARE SPECIFIC TO THEIR MISSION. I THINK IN TERMS OF THE STRUCTURE OF THE PLAN, IN TERMS OF MAYBE HAVING THESE MAJOR THEMES AND THE PRINCIPLES, THERE MIGHT BE SOME. I THINK THEY WOULD LIKE TO TRY TO HAVE ALL THE PLANS GENERALLY BE STRUCTURED THE SAME IN TERMS OF HOW THE PLAN, THE DIFFERENT CATEGORIES OF THE PLAN IN BROAD, BUT WHAT THEY'RE HOPE SUGGEST THAT IN IDENTIFYING THESE CROSS CUTTING THEMES THAT GO ACROSS INSTITUTES, INSTITUTES WILL SEE OPPORTUNITIES THAT WILL HELP ADVANCE THEIR MISSION AND ADDRESSING SOME OF THESE. SO I DON'T FINISH THAT ANSWERS THE QUESTION, BUT THEY DON'T WANT THIS TO IMPOSE ANYTHING ON THE ICs REALLY. >> PEOPLE MAY GIVEN THIS CONVERSATION LOOK AT THE NIN DS STRATEGIC PLAN, MANY MA'AM IN THE ROOM WERE INVOLVED IN THE 2008-2010 OR SO? WHERE WE AS OPPOSE TO DOING A BIG BROAD SPREAD, WENT ACTUALLY INTO THE WEEDS AND WE BROKE IT OUT INTO KIND OF A VISIONARY PLAN FOR NINDS AND THEN THAT WAS KIND OF THE BLUE SKY AND THEN DOWN INTO THE WEEDS, INTO A PLAN FOR BASIC RESEARCH, TRANSLATIONAL RESEARCH, CLINIC RESEARCH AND DISEASE RESEARCH AND THAT PLAN WAS A LONG PROCESS, MULTIPLE STAKEHOLDERS, MULTIPLE MEETINGS, LOTS OF GOOD INPUT AND REALLY DOES SERVE, I THINK FOR THE INSTITUTE, AS A CURRENT PLAN AS WELL. SO I ENCOURAGE TO YOU LOOK AT THAT. I SUSPECT AS PAUL SAID THAT WE'LL BE ASKED TO REVISIT OUR PREVIOUS STRATEGIC PLAN, UPDATE IT IN A TEMPLATE THAT'S GOING TO COME DOWN BASED ON THIS FRAMEWORK THAT YOU SAW. I WOULD ALSO EMPHASIZE PAUL'S POINT, WELL WHAT WE'VE SEEN SO FAR IS THE FRAMEWORK IN WHICH IT WOULD BE PUT TOGETHER, WE THINK THE AUTHOR IS GOING TO BE DR. COLLINS, HEAVILY DR. COLLINS AND HE'S NEVER BORING. SO I THINK IT'S NOT GOING TO BE DRY WHEN IT COMES OUT IS MY GUESS. >> GOOD POINT. >> WHETHER OR NOT THERE WILL BE A GUITAR TUNE MIXED IN WITH THE PLAN IS YET TO BE DETERMINED. [LAUGHTER] BUT HE'S GENERALLY HAS--HE'S VERY INSPIRATIONAL BUT I THINK THE POINTS THAT WERE MADE ARE REALLY QUITE GOOD ONES, THE TRANSNIH INSTITUTE ISSUES ARE ALTS ALWAYS THORNS IN OUR SIDE, I WAS TALKING TO DR. COLLINS ABOUT THE ISSUES THAT COME UP, WE ALMOST NEED AN INSTITUTE FOR THINGS THAT FALL BETWEEN THE CRACKS. BUT WE COULD PUT TOGETHER A BETTER WAY OF SOLVING THOSE ISSUES OURSELVES. AND AS BUDGETS GOT TIGHTER, YOU KNOW INSTITUTES HAD TO CONSERVE AND CONSERVE AND CONSERVE AND NOW IT'S BEEN 10 YEARS IN CONSERVING AND THINGS ARE PRETTY MUCH AT THE BREAKING POINT, SO THINGS LIKE THE NEUROSCIENCE BLUEPRINT, COME UP FOR DISCUSSION, SO THE NEUROSCIENCE BLUEPRINT IS WHERE ALL THE ICs GET TOGETHER AND PLAN NEUROSCIENCE SPECIFIC, BUT GENERAL TO ALL THE ICs THAT DO NEUROSCIENCE PROJECTS. SO FOR INSTANCE THE NRI CONNECTOME PROJECT TO GET THE CONNECTIONS WORKED OUT IN HUMANS USING THE BEST MR TECHNOLOGY, BLUEPRINT PROJECT AND THEY PUT MONEY TO A POT EVERY YEAR, AND IT WAS ABOUT ABOUT 40 MILLION A YEAR, AND THEN THAT WAS A BUDGET THEY USE FOR BLUEPRINT PROGECS. THE GROUP HAS DECIDED ON GOING FORWARD TO CHANGE THE STRUCTURE SO THEY'RE NO LONGER GOING TO PUT 40 MILLION IN THE POT. THEY WILL PUT A SMALL AMOUNT IN THE POT TO DO INFRASTRUCTURE PROJECTS LIKE TRAINING AND A PROJECT LIKE THE CONNECTOME, WOULD BE GROUPS OF ICs THAT WANT TO DO IT, WILL CALIFORNIA TOGETHER AND MAKE A PACT WITHIN THEMSELVES TO HAVE THAT PROGS EXPECT HAVE THE 40 MILLION USED AND THE STRESS ON THEM TO FIND THE WORK THAT'S MOST CENTRAL TO THEIR MISSION IS IS MAKING IT HARDER TO DO THIS IN THIS TIME. IT'S UNFORTUNATE IN MY MIEBD, UNFORTUNATE CONSEQUENCE OF WHAT'S HAPPENED. THE BLUEPRINT IS CHANGING WHAT IT CAN HAPPEN, IT CAN BE EFFECTIVE BECAUSE IT WILL BE INFRASTRUCTURE PROJECTS WE ALL DO TOGETHER, WE WILL PUT MONEY IN THE POT TO DO THAT, AND THEN I THINK, THERE'S ENOUGH INSIGHT AMONG DIFFERENT ICs TO SEE THAT THERE ARE PROJECTS THAT IF WE DO THEM TOGETHER, WE CAN GET THEM DONE. IF WE TRY AND DO THEM ALONE, WE'LL NEVER GET THEM DONE. THERE ARE CERTAINLY INSTITUTES IN THE BLUEPRINT THAT A LOT OF, AND THAT'S THE THING THAT LED TO THIS CHANGE AND THIS STRUCTURE, SO IT'S STILL GOING TO BE IMPORTANT GOING FORWARD, BUT IT DOES--IT DOES SPEAK TO THE ISSUE OF TRANSNIH STRENGTHENING TRANSINSTITUTE ACTIVITY HAS BECOME MORE DIFFICULT BUT IT'S--IT WAS PROBABLY MORE IMPORTANT NOW THAN EVER TO DO THAT. SO THAT WAS A REALLY GOOD POINT THAT PEOPLE MADE. THE COLLABORATION OF NCATS CLEARLY--THAT'S HIGH UP ON OUR PLATE. AND WE WORK WITH PET RA, WE TALK TO HER FREQUENTLY, WE TRY TO WORK OUT DEALS ON DIFFERENT PROJECTS, SO I THINK THAT'S GOING TO WORK WELL. I THINK THE TEAM SCIENCE ISSUE THAT DR. Mc BERNIE BROUGHT UP IS SOMETHING THAT'S GOING TO POINT IN TIME.PPLED WITH AT SOME THAT WE HERE, THAT CRITICISM FROM MANY DIFFERENT QUARTERS AND SO THE ISSUE THERE IS IF YOU WANT TO--IF THERE ARE MAJOR PROBLEMS THAT ARE FACING THE COUNTRY HEALTH WISE AND NEUROSCIENCE, IS IT MORE PRODUCTIVE TO GO OUT IN THE CURRENT SYSTEM WHERE IT'S VERY PI CENTRIC, A GRANT GOES TO A CERTAIN INVESTIGATOR AND THEY'RE ALL COMPETING AGAINST EACH OTHER, SORE IS THERE SOME--OR HAVE WE CREATED A MONSTER WHERE THE INCENTIVE SYSTEM THAT NIH USES, KIND OF PRECLUDES A TEAM, YOU KNOW BEING LOCKED IN A ROOM OR LOCKED IN FENCES IN NEW MEXICO SOMEWHERE UNTIL THEY FIGURE OUT HOW TO DO IT AND THEN THEY'RE ALLOWED OUT. SO I THINK THAT ISSUE'S GOING TO COME AND OUR INSTITUTE WHERE WE'VE BEEN DOING MORE AND MORE IS INSTEAD OF HAVING CENTERS THAT ARE INSTITUTIONALLY BASED, WE HAVE CENTERS THAT ARE PROBLEM BASED SO WE CALL THEM CENTERS WITHOUT WALLS SO THEY'RE NOT AT A CERTAIN EN--STRATEGIES TUITION BUT THEY'RE A TEAM OF PEOPLE ACROSS THE COUNTRY BUT THEIR FUNDED TO SOLVE A PROBLEM. SO WE'RE IN THAT DIRECTION, RIGHT NOW THE TEAMS ARE MAYBE THREE OR FOUR PIs WHICH WHO MAY HAVE EACH TWO OR THREE OTHER PEOPLE WORKED ON PROJECTS SO IT'S A LEVEL--NOT A LEVEL OF A HUNDRED PEOPLE, BUT A LEVEL OF 12 OR 15 PEOPLE. BUT I THINK THAT'S SOMETHING THAT WE REALLY, IT WOULD BE SOMETHING THAT NIH WOULD HAVE TO CHANGE ITS MECHANISMS TO MOVE INTO THAT, INTO THAT SPACE AND TRANSLATION IS IMPORTANT TO HEAR THOSE COMMENTS SINCE WE'RE CLEARLY TRYING TO DRIVE DISCOVERIES TOWARDS TRANSLATION AND AND WE'RE ALWAYS TRYING TO IMPROVE HOW WE DO THAT. OKAY, JOHN? >> YEAH, JUST ANOTHER THING THAT OCCURRED TO ME SITTING THERE TALKING WITH RON ABOUT--SO I'VE BEEN OUT OF MY PROGRAM DIRECTOR JOB FOR EIGHT MONTHS AND NINE DAYS, I THINK IT IS, IT IS NOW, ONE OF THE PROBLEMS, ONE OF THE PROBLEMS IS INTERNAL STAFF BURDEN AND I THINK THAT'S SOMETHING THAT NEEDS TO BE ADDRESSED ON AN NIH WIDE SCALE. WHEN I FIRST STARTED IT WAS MUCH, 10 YEARS BEFORE, IT WAS MUCH EASIER TO GET OUT THERE WITH THE COMMUNITY AND INTERACT WITH ALL THE PATIENT ADVOCACY GROUPS AND EVERYTHING, BECAUSE THERE WAS LESS ADMINISTRATIVE BURDEN ON PROGRAM DIRECTORS AND THIS IS NIH WIDE AS YOU KNOW I WAS ON COMMITTEES WHERE I TRIED TO COMBAT SOME OF THIS STUFF AND IT DAMPED IT DOWN. I THINK ANY CONSIDERATION OF REALLY OPTIMIZING HOW THE NIH FUNCTIONS, REALLY HAS TO INCLUDE TO WIN A VERY CAREFUL JOB OF OPTIMIZING USE OF THE STAFF YOU HAVE BECAUSE YOU REALLY HAVE TERRIFIC PEOPLE WHO COULD HAVE MUCH MORE IMPACT ON THE DISEASE COMMUNITIES THAN THEY DO. IF THEY'RE NOT BURDENED WITH MAKING SURE THAT--AND A GRANTEE HAS COMPLIED WITH THE PUBLIC ACCESS POLICY. WHICH, YOU KNOW YOU COULD HIRE SOMEBODY WITH A B. S. IN BIOLOGY TO DO THAT ACROSS THE ENTIRE INSTITUTE BUT I KNOW THAT THOSE KINDS OF THINGS FELL ON PROGRAM DIRECTORS AND IT MADE IT MUCH HARDER TO HELP BUILD THE PARTNERSHIPS TO HELP WORK WITH THE DISEASE COMMUNITIES, BECAUSE THIS IS THE 1.6 BILLION DOLLAR INSTITUTE BUT WHEN YOU LOOK AT THE MISSION, THE ALL THE WAY DOWN TO DUCHENNES, IT'S NOT A LOT OF MONEY SO YOU HAVE TO LEVERAGE THE RESOURCES SO I PUT IN A PLUG THAT THE PLANNING PROCESS NEEDS TO BE TO OPTIMIZE ALL THE GOOD PEOPLE THAT YOU'VE GONE THROUGH ALL THE TROUBLE TO GET. >> GOOD COMMENT. BUT IT CAN ONLY COME FROM AN INSIDER. [LAUGHTER] SO WE ARE ACTUALLY GOING TO EMBARK ON A WORKFORCE ANALYSIS TO JUST DO EXACTLY WHAT YOU SAID IN TERMS OF FIGURING OUT WHAT KIND OF PEOPLE WE NEED TO DO THE JOB AND FREE PEOPLE UP FOR WHAT THEY'RE BEST AT DOING, SO AGAIN, RESOURCES ARE GOING TO LIMIT IT IN A SENSE BUT I THINK WE CAN DO EVEN BETTER THAN WE ARE NOW WITH THE RESOURCES WE HAVE. GOOD POINT. SO ONE, NEXT SLIDE IS THESE ARE THE QUESTIONS WE WANT TO ADDRESS THIS AFTERNOON'S BREAK OUT GROUP FOR THOSE OF YOU WHO ARE INTERESTED IN COMING SO I WANT TO PUT THOSE UP NOW TO GET THEM OUT THERE, SO YOU CAN START THINKING ABOUT THEM. SO FIRST, HOW CAN NIH LEVERAGE--THE AREAS OPPORTUNITY TO ADVANCE OUR MISSION AND MORE SPECIFICALLY HOW CAN WE PARTNER WITH YOU TO LEVERAGE THESE OPPORTUNITIES THAT ADVANCE YOUR DISEASE AREAS. HOW SHOULD NIH BALANCE PRIORITIES TO IDENTIFY THE SETTING PRIORITIES EXAMPLE IN TERMS OF DISEASE BURDEN, SCIENTIFIC OPPORTUNITY, RARE DISEASES, AND THEN LASTLY WHAT ARE YOUR THOUGHTS ON HOW NIH SHOULD ADDRESS THOSE STEWARDSHIP PRINCIPLES AND I THOUGHT SPECIFICALLY YOU WOULD BE INTERESTED IN TRAINING PARTNERSHIPS AND AND FUNDING DECISIONS BUT IF THERE'S ARE OTHERS YOU WANT TO TALK ABOUT, WE WOULD BE OPEN TO DISCUSSING THOSE AS WELL. SO AGAIN I WANT TO GO THROUGH THOSE AND GET THOSE OUT THERE SO CAN YOU CHEW ON THAT IF YOU'RE COMING TO THE MEET THANKSGIVING AFTERNOON. >> WELL, THANK YOU DR. SOKOLOFF. >> [ APPLAUSE ] >> SO WE'RE MOVING INTO OUR FIRST PANEL OF THE MEETING AND WE'RE PLEASED TO BRING UP RON BARTEK, AND ILENE, AND THIS IS STRATEGIES FOR A RESEARCH PORTFOLIO AND OUR MODERATORS RON WAS THE CONFOUNDER AND WITH THE RESEARCH ALLIANCE AND A BOARD NUMBER OF NORD, AND SERVED AS FOUR YEARS IN THE NINDS COUNSELS AND I WILL ILENE IS SERVING ON THE COUNSELS AND I WILL SHE'S VICE PRESIDENT OF HOPE THROUGH HEMATOMAS, AN ORGANIZATION THAT SHE FOUNDED AND SUPPORT FOR PATIENT CAREGIVERS AND HEALTHCARE PROVIDERS IN HER DISEASE. SO ON THE BANLE WE HAVE BRAD MARCUS FROM THE CHILDREN'S PROJECT, JOHN PORTER FROM PARENT MUSCULAR DYSTROPHY; FLORRIAN EER, AND KEVIN Mc NAUGHT, AND LAURA MAMOUNAS,. >> YOU WANT TO TAKE IT AWAY? >> ABSOLUTELY. WE ARE COMMITTED TO BEING BRIEF, WE WILL NOT GIVE PRESENTIONS AS CO MODERATORS FOR A COUPLE REASONS. ONE IS THAT THESE PANELISTS ARE ABSOLUTELY AWESOME. WE WANT TO GET RIGHT TO THE CHASE, HERE, THEY ARE GIFTED IN MANY WAYS AND INCREDIBLY ACCOMPLISHED IN THIS ARENA AS WELL AS OTHERS AND THE SECOND REASON IS THAT WALTER ALREADY DID OUR JOB, OF SETTING THE STAGE FOR THIS PANEL DISCUSSION AND OPENING REMARKS YESTERDAY, AS YOU MIGHT RECALL, HE INDICATED THAT BASIC SCIENCE SETS THE FOUNDATION FOR TRANSLATIONAL AND CLINICAL RESEARCH WITHOUT THAT BASIC FOUNDATION, OR CLINICAL RESEARCH ARE EITHER IMPOSSIBLE OR VERY DIFFICULT INDEED. SO FOR THOSE TWO REASONS WE WILL BE VERY BRIEF IN OUR INTRODUCTION AND GET TO VERY BRIEF REMARKS FROM EACH OF OUR PANELISTS. I WOULD LIKE TO SAY AT THE OUTSET HOWEVER, THAT YESTERDAY'S DISCUSSIONS WERE EXCELLENT IN ALL SORTS OF WAYS. MOST OF THE BUZZ AT THE END OF THE DAY YESTERDAY, INCLUDING THE RECEPTION IS THAT DAY ONE OF THIS PANEL OF THIS FORUM WAS PROBABLY THE BEST DAY OF ANY OF THE FORATHE NINDS PATIENT GROUP FORUM AND WE CERTAINLY WANT TO KEEP THE PACE TODAY. THAT EXCELLENT DISCUSSION OF PATIENT REGISTRIES AND NATURAL HISTORY DATABASES WITH WHICH WE BEGAN YESTERDAY'S DISCUSSIONS, THAT TOO, THOSE TOO KOOBT BE ISOLATED FROM BASIC SCIENCE, EITHER. IF YOU HAVE NOT TAKEN THE STEPS OF DEVELOPING A BASIC RESEARCH PORTFOLIO FOR YOUR DISEASE, AND YOU DON'T HAVE A CLEAR UNDERSTANDING OF YOUR BASIC DISEASE MECHANISMS AND YOUR--YOU KNOW MECHANISMS OF DAMAGE AND CONSEQUENT POTENTIAL THERAPEUTIC MECHANI OF ACTION, THAT NATURAL--THAT PATIENT REGISTRY A NATURAL HISTORY DATABASE CAN BEGIN TO LOOK A WHOLE LOT LIKE SIMPLY A CATALOG OF DISEASE SYMPTOMS. AND CATALOG OF DISEASE PROGRESSION AND THAT'S NOT YOUR OBJECTIVE. YOU WANT TO GET TO TRANSLATIONAL AND CLINICAL RESEARCH. SO YOU NEED TO UNDERSTAND ENOUGH--YOU NEED TO CHARACTERIZE, USE YOUR BASIC RESEARCH PORTFOLIO TO CHARACTERIZE YOUR DISEASE TO UNDERSTAND THE BASIC BIOLOGICAL UNDERLYING MECHANISMS OF DAMAGE AND THEREFORE POTENTIAL THERAPEUTICS. THAT WAY YOU CAN USE YOUR NATURAL HISTORY DATABASE AND PATIENT REGISTRY TO CHANGE SHOTS IN THE DARK, CLINICAL SHOTS IN THE DARK TO WELL INSTRUCTED CLINICAL SHOTS ON GOAL BECAUSE YOU KNOW WHAT YOU'RE AFTER, YOU'RE YOU KNOW WHAT YOUR TARPGETS ARE AND HAVING SAID THAT, I WOULD SAY THERE'S NO BETTER PLACE THAN HERE WITH THE NINDS TO DISCUSS THIS MATTER. AGAIN, NOT ONLY IS THE NINDS, LEADING THE CHARGE IN NEUROSCIENCE BASIC RESEARCH, AS WALTER SAID YESTERDAY, THE LARGEST SINGLE FUNDER OF NEUROSCIENCE BASIC RESEARCH, AND YOU KNOW, GOING BACK AGAIN TO THE FACT THAT IF YOU DO YOUR BASIC RESEARCH, YOU CAN GET YOUR PATIENT REGISTRY, GET YOUR NATURAL HISTLY DATABASE AND THOSE TWO THINGS IN COMBINATION WITH THE CLINICAL NET WORK YOU CAN BUILD BY INVESTING IN YOUR CLINICAL SCIENTISTS, TO DEVELOP YOUR NATURAL HISTORY DATABASE, ALL THOSE THINGS TOGETHER BECOME THE LOW HANGING FRUIT THAT WILL ATTRACT INDUSTRY PARTNERS, THAT YOU WILL NEED FOR ADVANCE THERAPY DEVELOPMENT. I LIKE TO THINK OF OUR DISEASE GROUP AS GROWING LOW HANGING FRUIT. BECAUSE WE CAN'T DO IT ON OUR OWN, NONE OF CAN YOU DO IT ON YOUR OWN, YOU THAN SO YOU'VE GOT TO BUILD GROW THE FRUIT THAT WILL DRAW IT TO YOUR SLIDE, SO NO BETTER PLACE THAN THE NINDS DISCUSSION, I CAN'T IMAGINE A BETTER PANEL TO LEAD US THROUGH THAT DISCUSSION, FOUR OF US HAVE SERVED OR ARE SERVINGOT NINDS, NATIONAL ADVISORY COUNCIL, TWO OTHERS HAVE SERVED OR ARE SERVING ON THE NINDS PROGRAM DIRECTORS. WE WILL DEVOTE ABOUT HALF THE TIME ALLOTTED TO THIS PANEL TO YOUR PARTICIPATION IN THIS DISCUSSION. THIS HAS TO BE A TWO WAY STREET. WE'VE ALTERED THE ORDER OF PRESENTATIONS TO CONFORM WITH WHAT MADE MOST SENSE TO US. AND WE WILL BEGIN WITH--ILENE AND I WILL MAKE PREV INTRODUCTIONS OF EACH SPEAKER. I WILL BEGIN WITH JOHN PORTER, PARENT PROJECT MUSCULAR DYSTROPHY UNTIL TAKINGOT NEW RESPONSIBILITY, JOHN HAS INDICATED EARLIER WAS NINDS PAM DIRECTOR FOR A NUMBER OF DISEASES, INCLUDING SPINAL MUSCULAR ATROPHIES, AND THE MUSCULAR DYSTROPHYS. SO YOU'RE OUR LEAD OFF HITTER, JOHN. >> THANKS, RON. I CAN'T HELP BUT SAY SOMETHING TO START JUST TO EMPHASIZE YOUR OVERALL THEME. THE IDEA OF LOOKING AT WHAT THE OVERALL PANELS ARE TALKING ABOUT, IS WHAT THEY'RE DOING IN PARALLEL, DEVELOPING NATURAL HISTORY AT THE SAME TIME TRY TO FIGURE OUT WHAT THE HECK THIS GENE YOU HADITATION DOES MECHANISTICALLY FOR THE DISEASE AND THE BEST WAY KIEMPHASIZE THAT IS TO QUOTE ED KAY, SO WHEN ED WAS WITH GENSIGN, HE DEVELOPED A SUCCESSFUL TREATMENT FOR LYSOSOMAL STORAGE DISORDERS, BUT THIS IS EARLY DAYS AND AT A GOT TO THE POINT OF BEING READY TO LAUNCH CLINICAL TRIALS AND THEY DIDN'T KNOW WHERE THE PATIENTS WERE, THEY DIDN'T KNOW THE NATURAL HISTORY OF THE DISEASE, THEY NOT KNOW WHAT END POINTS IN THE CLINICAL TRIALS AND THIS WAS A SUCCESSFUL THERAPY BUT WHAT ED SAID ABOUT THIS IS IF HE HAD RECOGNIZED IF THEY HAD RECOGNIZED THAT GENSIGN, WHAT WHAT A BARRIER IT WAS TO TO NOT KNOW THE NATURAL HISTORY OF THE DISEASE, NOT TO PICK OUT THINGS CAN YOU DO WITH REGISTRIES, THEY MAY HAVE NEVER LAUNCHED THIS DRUG DEVELOPMENT PROGRAM TO BEGIN WITH AND THAT WAS A SUCCESSFUL DRUG. SO TO ME THAT'S' PRETTY STRONG INDICTMENT ABOUT MAKING SURE HAVE YOU THINGS IN PLACE. OKAY, I'VE ALREADY CUT INTO AT LEAST HALF THE TIME ALLOCATED JUST WITH THAT REMARK. NOW, THE POINT THAT I WANTED TO MAKE IS REALLY ASKING THE QUESTION VERY SERIOUSLY ABOUT WHERE THE CENSUS IS THE BASIC SCIENCE PANEL, WHERE YOUR SCIENCE IS AT THIS POINT IN TIME. WHETHER YOU'VE GOTTEN THE GENE OR JUST FIGURED OUT THE PRECIPITATING EVENT FOR THE DISEASE OR WHETHER YOU'VE BEEN WORKING ON YOUR DISEASE FOR 25 YEARS AND YOU KNOW A LOT OF THAT. I THINK YOU HAVE TO STEP BACK AND REASSESS EXACTLY WHERE YOU ARE IN TERMS OF THE BASIC SCIENCE SO THE GENE WAS DISCOVERED IN THE LATE 80S SO IT'S BEEN QUITE A FEW YEARS SINCE THEN AND I THINK PEOPLE IN THE FIELD FOR DUCHENNE'S MUSCULAR DYSTROPHY WOULD BE A CURE QUICKLY. WELL, WE HAVE UPCOMING ADVISORY MEET NEGLIGENCE NOVEMBER BUT IF THOSE ARE APPROVE THOSE WILL BE OUR FIRST APPROVED DRUGS IN THE U.S. FOR THE DISEASE. SO IT DOESN'T HAPPEN QUICKLY. SO I'D JUST LIKE TO DIRECT A FEW COMMENTS TOWARDS FOLKS THAT ARE REALLY AT AN EARLY STAGE IN TRYING TO FIGURE OUT DISEASE MECHANISMS. I THINK THAT THERE'S A NUMBER OF WAYS YOU CAN GO THERE. FIRST YOU HAVE TO GENERATE. WE ALL GO THROUGH THIS, IT'S A REGULAR CYCLE, IT'S GOOD TO GET ADVOCATEY GROUPS TOGETHER AND TALKING, YOU HAVE TO FIGURE OUT THE DISEASE MECHANISM, SO YOU HAVE TO GET A CRITICAL MASS OF SCIENTISTS TOGETHER IN THE FIELD. YOU HAVE TO GET PEOPLE INTEREST SAID IN WORKING ON YOUR DISEASE AND THAT CAN BE HARD, RIGHT? YOU CAN BRING PEOPLE IN THAT YOU NEED PARTICULAR TECHNIQUES, CAN YOU BRING THAT THE WORKING ON IN RELATED FIELD. ONE INTERESTING THING, I SAW THE INCLUSION, I SAW THE BODY MYOCYTEUS PEOPLE DO, WHERE THE ACCUMULATES IN MUSCLES INSTEAD OF NEURON SYSTEM THEY BROUGHT IN PEOPLE FROM THE ALZHEIMER'S DISEASE COMMUNITY TO THEIR MEETINGS AND HAD THEM THERE AND TRIED TO GET THEM BRANCHING OUT IN IT CAN BE CRITICAL TO GET PASSED THAT STEP. I SAW THE MUSK LOW DYSTROPHY FIELD SUFFER BECAUSE THEY A DIFFICULT GENETIC MECHANISM. IT WAS VERY HARD TO FIGURE OUT. JUST ABOUT EVERY NIH APPPLICATION THAT GLEN KNUCKLES MY COLLEAGUE AT NIAMS, HE TOOK OVER MY JOB AT NINDS AND MOVED OVER FROM MUSCULARRIVITY COFFEE, AND NOW WE'RE TRYING TO HELP THESE PEOPLE. EVERY GRANT LOOKED EXPLORATORY BECAUSE THEY DIDN'T UNDERSTAND THE DISEASE MECHANISM. EXPLORATORY, THE TWO BAD WORDS IN STUDY SECTIONS, DESCRIPTIVE AND FISHING EXPEDITION, DEAD. YOU'RE LIKE D. O. A. IN STUDY SECTION. SO HAD TO FIGURE OUT THE DISEASE MECHANISM AND WHEN THAT GOT FIGURED OUT IN 2011, THE DISEASE STARTED TAKING OFF. AND THE LAST FSH SOCIETY MEETING I WENT TO THEY HAD A NUMBER OF COMPANIES COME TO THE FIELD, COME TO THE MEETING SO I THINK THAT'S HUGELY IMPORTANT IMPORTANT TO WORK TOWARD THAT. SO MY OWN ORGANIZATION, WE'VE BEEN SUCCESSFUL IN BUILDING THAT KIND OF APPROACH AND GETTING COMPANIES ENGANG SAID IN THE DISEASE AND OUR LAST DRUG DEVELOPMENT ROUPED TABLE WE HAD 27 COMPANIES COME TO THAT SO I THINK YOU HAVE TO STEP BACK, BUT EVEN IN OUR STAGE WE DON'T COMPLETELY UNDERSTAND HOW THE DYSTROPHY MUTATION TURNS INTO THE DEATH OF MUSCLE FIBERS. WE HAVEN'T WORKED EVERYTHING OUT. THERE'S PROBABLY TARGETS OUT THERE WE HAVEN'T WORKED OUT: SO WHATEVER STAGE, MY MESSAGE IS WHATEVER STAGE YOU'RE AT, YOU NEED TO LOOK AT ENGAGING BASIC SCIENCE WHETHER YOU HELP INVESTIGATORS GET NIH GRANTS BY PROVIDING SEED FUNDING BY ATTRACTING POST DOCS TO THE FIELD, MAKE SURE THAT YOU'RE WORKING WITH A PROGRAM DIRECTORS HERE AS I SAID, A COUPLE MINUTES AGO, HAVE YOU A DEDICATED GROUP OF PEOPLE HERE. NTHANK YOU FOR A REALLY INSPIRING LEAD OFF. OUR NEXT SPEAKER IS OUR GOOD FRIEND BRAD MARGUS, WHO IS IN CHARGE OF THE A-T CHILDREN'S PROG EXPECT HE'S WITH SCIENTISTS INCORPORATED AND HE HAS ALSO SERVED ON THE NINDS NATIONAL ADVISORY COUNCIL. I WAS CEO A COUPLE COMPANIES AGO BUT I'M HERE TODAY AS A DAD OF TWO KIDS WITH A-T AND WE HAVE AN ORGANIZATION LIKE MANY OF YOU, SMALL, NONPROFIT THROUGH NO SCH PEOPLE WHO HAD THE DISEASE, SO WE THROUGH GRASS ROOTS EFFORTS RAISED ONE OR $2 MILLION A YEAR, BUT WE ONLY HAVE FOUR OR FIVE KIDS IN THE U.S. WITH THE DISEASE AND WE'VE BEEN PLUGGING AWAY. I GUESS MY TIDBIT, I WOULD LIKE TO SAY THAT, YOU KNOW BIOLOGY IS HARD, I ENVY PEOPLE IN THIS ROOM WHO HAD BETTER SUCCESS AT UNDERSTANDING THE BIOLOGY OF THE DISEASE AND FINDING SOMETHING YOU WANT TO DO WITH IT BUT ON THE ONE OF THE THINGS WE'VE DONE OVER THE YEARS WE'VE GOT VERY OBJECTIVE ADVISORY BOARDS AND PEOPLE WHO ARGUE OUT EVERYTHING, SO THERE'S NO BIAS THAT CREEPS IN AND WE'VE TRIED TO DO THINGS WITH BEST PRACTICES BUT WE'VE ALSO THOUGHT OF OURSELVES AS A MININIH AND I THINK THAT'S A DOWN FALL. AND BY THAT I MEAN WE LET PEOPLE KNOW WE CAN FUND RESEARCH, MAYBE WE STEER CERTAIN PEOPLE OR ENCOURAGE CERTAIN PEOPLE TO MAKE PRINTS AND THEN HAVE SMART PEOPLE REVIEW THEM AND HAVE TELL US IF THEY'RE GOOD PEOPLE WITH GOOD IDEAS AND YOU NEVER KNOW WHERE GOOD IDEA CANS COME FROM AND THEY'RE INDEPENDENTLY INITIATED IDEAS, AND IF THEY'RE GOOD WE FUND THEM AND MAYBE NOT AS MUCH AS THEY WANT BUT AT SOME POINT YOU CAN KEEP DOING THE BIOLOGY AND LEARNING INTERESTING THINGS ABOUT THE DISEASE WITHOUT IN MY VIEW MAKING PROGRESS TOWARD AN ACTAL TREATMENT. SO PARTLY BECAUSE MY DAY JOB IS IN BIOTECH COMPANY WHERE YOU PUT A BUSINESS PLAN TOGETHER AND HAVE YOU INVESTOR WHO IS REALLY HOLD YOU TO THE FIRE. I'VE KIND OF TAKEN A MORE DIFFERENT STAINS RECENTLY AND THAT IS TO TRY TO ENVISION EVERY POTENTIAL TREATMENT THAT MIGHT COME ABOUT FOR THIS DISEASE. SO - IT'S A SINGLE GENE DISEASE, THE FIRST ONE THAT COMES TO MIND IS TO REPLACE THE BAD GENE WITH A GOOD GENE. GENE THERAPY AND TODAY'S WORLD THAT'S COMING BACK TO LIFE, IT DIED FOR A WHILE BUT THERE'S SEVERAL COMPANIES AND A LOT OF ACADEMICS PLAYING WITH THIS AND THE VIRAL VECTORS YOU USE TO DELIVER THE GENE, THE BIGGEST GENE THAT SEEMS TO BE CARRYABLE IS ABOUT OUR OR 5000 BASES AND THE CODING REGION OF OUR GENE IS ABOUT 9000, SO WE'RE STUMPED BUT WHAT I'VE DONE IS FOR EACH STRATEGY THEY ENVISIONED, I TRIED TO IDENTIFY WHAT THE NEXT OBSTACLE IS, NOW WE THINK DOWN THE ROAD ABOUT END POINTS AND ALL THE THINGS WE NEED IF WE HAVE A DRUG AND CLINIC, BUT IT'S IMPORTANT FOR EACH OF US TO KNOW OURSELVES TO TELL OUR DONORS TO HELP FOR FUNDRAISING AND FOR US TO TELL OUR PROGRAM DIRECTOR WHEN IS WE GET TO MEET THEM AT NIH HA IS THE ONE THING THAT'S REALLY HOLDING US BACK? IF WE DON'T KNOW THOSE, THEN YOU'RE KIND OF PLAYING AROUND. WE WOULD LIKE TO HAVE OUR ORGANIZATIONS FULL BECAUSE WE PUT IT OUT OF BUSINESS BY FINDING A CURE, SO BESIDES GENE STRATEGY, YOU ARE FAMILIAR WITH THEM, WE HEAR ABOUT THEM, BUT ONE WOULD BE IF YOU CAN'T PUT A NEW COPY OF THE GENE IN THERE, MAYBE THEY IGF NORMUTATIONS WITH THE KIDS DISEASE AND AXON SKIPS AND READ THROUGH COMPOUNDS THAT ARE GOING TO CLINIC MIGHT BE INTERESTING. YOU'VE HEARD ABOUT IPS CELLS AND POTENT STEM CELLS AND MAKES THEM FROM THE KIDS OF YOUR DISEASE, RHYTHM AND CULTURE AND FORM THEY CAN TURN INTO ANYTHING. MAYBE FIX THE GENE IN THEM AND TURN THEM INTO BRAIN CELLS STICK THEM BACK IN ASK AND MAYBE THEY'LL DO SOMETHING. IT'S A GREAT IDEA AND IF NIH FUNDED AND NINDS, DID IT WOULD TURN ME ON AND MAYBE IF IT'S NOT FOR MY KID'S DISEASE, GROWTH FACTORS ARE THESE THINGS THAT ARE IN OUR BRAINS ANYWAY, BUT THERE HAVE BEEN STUDIES SHOWING IF YOU INCREASE THE GROWTH FACTORS REGARDLESS OF WHY CELLS ARE DYING MAYBE THEY'LL KEEP THEM ALIVE LONGER AND THE KID WILL STAY OUT OF A WHEELCHAIR LONGER. THE BIG HOT THING IS INFLAMMATION IN THE BRAIN. SO FOR A LOT OF BRAIN DISEASES, SOMETHING CELS CAUSING THE CELL DEATH BUT PEOPLE BELIEVE THIS OVERACTIVE INFLAMMATORY RESPONSE OR RUN AWAY MACROPHAGE OR DIFFERENT THINGS LIKE THAT WILL MAKING THE NEUROIMAGING WORSE AND IF YOU COULD PLAY A ROLE WITH INFLAMMATORYS OR COMPOUNDS OUT THERE YOU COULD DO IT AND THEN THE MOST COMMON WAY FOR THE DRUG PERSPECTIVE IS DO A LOT OF BIOLOGY FROM THE PATHWAY DOWN FROM THE GENE THAT'S SCREWED UP BUT IF YOU COULD INHIBIT IT OR BROCK IT WOULD CORRECT THE DISEASE. SO YOU'RE LOOKING FOR A PROTEIN YOU CAN INHIBIT OR ACTIVATE OR YOU'RE LOOKING FOR A CELLULAR FEATURE, A DEFECT IN CELLS FROM THE PATIENTS THAT ARE ABNORMAL LIKE MITOCHONDRIAL CELL CYCLE DEFECTS OR A LOST DIFFERENT THINGS, IF YOU CORRECT THOSE IT WOULD BE CLINICALLY RELEVANT. THATTATE FINE PRINT. HOW DO I KNOW IT'S CLINICALLY RELEVANT AND MY KIDS DISEASE, WE FIND A MILLION THINGS ROCK AND EVERYTHING WE LOOK AT IS NEVER NORMAL BUT WE THEY'D TO KNOW WHICH IS RELEVANT CLINICALLY, IF IT WERE AND THERE'S ACTUALLY THIS WHOLE WORLD, NOW OF PEOPLE WHO ARE BECOMING INTERESTED IN RARE DISEASE AND INDUSTRY AND THEY CAN TAKE IT AND RUB WITH IT AND I KNOW THE CHEMISTS AND HIGH THROUGH PUT SCREENERS AND HERE AT NIH, THERE'S PEOPLE THAT WILL TAKE IT AND RUN WITH IT AT NCATS. BUT THE TRICKY SIDE IS WE MAYBE FORGET ABOUT THE BIOLOGY, AND I CAN SHOW YOULET PROTEIN BIOLOGY THAT INTERACT WITH MY KID'S DISEASE, IT'S LIKE A LONDON SUBWAY MAP AND STILL WE DON'T HAVE THE THING WE NEED TO KNOW. SO THE LAST AREA WOULD BE CIRCUITRY. THERE'S NOTHING CAN YOU DO, FORGET THE BIOLOGY, WISH WE NEVER EVEN FOBBED THAT DAMN GENE AND JUST SAY, WE KNOW FROM MRIs AND STUFF THAT HAVE YOU A ROT OF CELLS DYING IN THE CEREBELLUM, WHAT HAPPENS WHEN THAT HAPPENS? HOW DO YOU GET FROM THAT TO A PHASE FOR EXAMPLE? SO THAT'S WHERE THE CIRCUIT PEOPLE KICK IN AND THERE'S THIS WHOLE WORLD OF PEOPLE THAT DON'T CARE ABOUT MICROBION BUT RECORD BRAIN CELLS ALL THE TIME. HOW DO I GET THEM INVOLVED AND THAT'S A WHOLE OTHER AREA WE'RE INTERESTED IN. SO THOSE ARE IDEAS I THROUGH OUT BUT THERE ARE SEVEN SPECIFIC DETAILED THERAPIES I CAN ENVISION, IF WE MADE PROGRESS ON ANY ONE OF THEM, WE WOULD BE THERE. SO I HAVE SOMETHING CONCRETE TO SHOW DONORS AND SHOW FAMILIES THAT WE AREN'T JUST BIDDING ON ONE PLAN, WE HAVE A LOT. BUT IT'S HELPFUL. SO YESTERDAY WE MET WITH PROGRAM DIRECTORS IF WE COULD SEE WHAT THE BLOCKS ARE, FIRST THEY MIGHT TELL ME, HEY, BRAD, YOU'RE WRONG. ACTUALLY, THROUGH YOUR GENE TOO BIG TO CARRY WITH THE VIRAL VECTOR BUT THERE'S THIS GUY IN OHIO WHO'S PLAYING WITH TAKING HALF OF YOUR GENE AND PUTTING IT IN ONE VECTOR AND UTRING IT IN ANOTHER VECTOR AND SIGNALING THEM TOGETHER AND PUTTING IT TOGETHER IN YOUR BRAIN AND THERE'S A WAY WE MIGHT OVERCOME THAT OR WHATEVER. OT BIOLOGY SIDE, THE BIGGEST PROBLEM WITH OUR DISEASES WE HAVE ANIMAL MODELS WE MADE AND THE MICE AND THE MONKEYS AND WHERE MICE AND PIGS AND RATS THAT WE'VE MADE TO DATE DON'T HAVE A NEUROLOGICAL PROBLEM. THE ONLY PEOPLE WHO SEE THE PROBLEM ARE PEOPLE WHO MADE THEM BUT THE REST OF US CAN'T SEE IT. WE HAVE ATP PIGS NOW THAT ARE FUNDED FOR YEARS AND FUNDED FROM SBIR, AND WENT TO VISIT THEM AND SPEND HOURS WITH THEM AND THE LADY IN CHARGE OF THE BIG FACILITY, KINDLY SPRAY PAINTED PINK ON ALL THE ONES THAT HAD THE GENETIC GENE KNOCKED OUT SO I COULD SEE WHICH ONE IT WAS. LITTLE CLUE, WHEN THEY HAVE TO SPRAY PAINT THE BIG, YOU KNOW IT'S NOT GOING TO HAVE A REAL VOWBZ DISEASE. OKAY? --OBVIOUS DISEASE, OKAY? BUT I'LL CLOSE BUT THIS IS IMPORTANT BUT ONCE I HAD MY LIST, AND AGAIN I HOPE IT'S VERY WRONG, I HOPE MY OBSTACLES AREN'T OBSTACLES OR MAYBE THERE'S AN EIGHTH OR NINTH OR 10th STRATEGY I HAVEN'T THOUGHT OF, AND THAT'S MY DREAM. BUT THE NIGHTMARES I HAVE IS THAT 20 YEARS FROM NOW WE WILL LEARN THIS THING RIGHT IN FRONT OF THAWS WE NEGLECTED TO FOLLOW UP ON AND IT ENDED UP BEING THE TREATMENT. BUT MORE RECENTLY I BEGAN SHARING THIS LIST WITH VENTURE CAPITAL FORMS AND OTHER INVESTORS THAT HAVE TO KNOW WHAT THEIR PORTFOLIO COMPANIES DO AND IF THEY'VE GOT SOMETHING COOKING AND SOME OF THOSE COMPANIES OR ACADEMIC COMPANY, IT'S POSSIBLE THAT WE HAVEN'T HEARD, IT'S POSSIBLE NIH PROGRAM DIRECTORS HAVEN'T HEARD ABOUT IT BUT THEY SAY TO YOU, NUMBER THREE, HAVE YOU A CHANCE. SO I WOULD ENCOURAGE TO YOU BE CAREFUL AND NOT FALL IN THE TRAP WHERE YOU PASSIVELY SIT BACK THERE AND THE LAST THING I'LL SAY IS THAT I'VE BEEN ON A FEW RETREATS I'VE BEEN INSOFTED TO FOR OTHER DISEASE ORGANIZATION WHERE IS HAVE YOU A WEEKEND TOGETHER AND DURING TIN DINNER, I PREPARE MYSELF BY ASKING THE PERSON I'M SITTING NEXT TO, WHAT'S HAPPENING IN YOUR DISEASE? AND THE WORST THING IN THE WORLD TO HEAR IS JOHN SAY, WELL, WE GOTTA GO OVER AND TALK TO MARY SHE'S OUR SCIENTIFIC COORDINATOR, WE DON'T REALLY KNOW. YOU CANNOT BE THAT. THIS IS WAY TOO IMPORTANT. WE'RE NOT THAL FOR FUN. SO WHAT I SAID MAY SOUND LIKE HARD SCIENCE, IT'S REALLY NOT. HAVE YOU TON IT ENOUGH TO LIVE AND BREATHE IT AND BE PASSIONATE ABOUT IT SO CAN YOU GET PEOPLE TO WORK ON IT. THANKS. >> BRAD, THANK YOU FOR THOSE REMARKS, AS A PARENT OF A CHILD WITH A DISEASE, I WILL WALK AWAY WITH INFORMATION AS WELL. I WANT TO INTRODUCE JOHN PORTER PARENT PROJECT MUSCULAR DYSTROPHY, AND HE'S ON THE BOARD OF DIRECTORS FOR THE NATIONAL ORGANIZATIONS NASSATION FOR RARE DISORDERS, I SUSPECT NATION OF OUR ORGANIZATIONS PARTICIPATE IN THAT AS WELL. THANK YOU. >> THANK YOU ILENE AND GOOD MORNING SO MY ORGANIZATIONS NET TOURET ORGANIZATION WE'VE BEEN AROUND FOR ABOUT 40 YEARS. AFTER ALL THIS TIME WE REMAIN THE ONLY NONPROFIT ORGANIZATION THAT CONTINUES TO DRIVE AND SUPPORT RESEARCH AND CARE FOR PEOPLE WITH TORRETTE'S SYNDROME AND THIS IS SOMETHING WE'VE EMBRACED OVER THE YEARS, WE SHARE THAT WE REMAIN FRONT AND CENTER OF THE FIELD IN TOURET'S SYNDROME. SO THIS HAS GIVEN US A GREAT DEAL OF RESPONSIBILITY AS WE HAVE--WHICH WE HAVE EMBRACED AND I WANT TO BRIEFLY SHARE WITH YOU THE KIND OF THINGS WE DO. ONE OF COURSE IS RELATIONSHIP MAKING OR MATCH MAKING AS I TEND TO PUT IT. IN FACT, WE'RE NOT A LARGE FIELD BUT WE RECOGNIZE THAT THERE ARE INSTITUTIONS, THERE ARE SCIENTISTS SPREAD ACROSS THE COUNTRY, AND IN FACT, THERE ARE MANY SCIENTISTS AND CLINICIANS OVERSEAS AS TO WHAT WE TRY ON DO OVER THE YEAR SYSTEM TO BRING ALL OF THESE ELEMENTS TOGETHER AND RON IS RIGHT IN THAT. YOU ARE NOT ALONE. AND BY GOING AT THIS ALONE, I THINK IT'S A TREMENDOUS ADVANTAGE TO THE CAUSE THAT YOU REPRESENT. SO WHAT WE HAVE DONE OVER THE YEAR SYSTEM TO ESSENTIALLY DO MATCH MAKING AND RELATIONSHIP BUILDING. WE'VE DONE THAT I THINK VERY WELL WITH NINDS, WE'VE REACHED OUT TO VARIOUS ACADEMIC INSTITUTIONS, AND MORE RECENTLY, WE'VE BEEN WORKING WITH A NUMBER OF INDUSTRIES SO THAT THESE RELATIONSHIPS AND THESE INDIVIDUALS AND INSTITUTIONS CAN WORK TOGETHER AND IN A COLLABORATIVE WAY TO ADDRESS MANY OF THE PROBLEMS AND THAT WE RECEIVE AND I'M CERTAIN THIS IS PRETTY MUCH THE SAME FOR THE OTHER ORGANIZATIONS THAT ARE REPRESENTED HERE IN THAT COLLABORATION IS KEY IN TERMS OF HOW WE DRIVE RESEARCH AND DEVELOPMENT AS WE MOVE FORWARD. SO THAT IS SOMETHING THAT WE'RE PROUD OF AND SOMETHING THAT WE HAVE BEEN RELATIVELY SUCCESS ENVELOPE DOG OVER THE YEARS. WE HAVE A TREMENDOUS GREAT RELATIONSHIP WITH NINDS AND MANY OF THEM HERE AT MY LEFT, SO WE BUILD THESE RELATIONSHIPS OVER THE YEARS AND THEY HAVE SERVED US VERY WELL. THEY SERVE THE COMMUNITY VERY WELL AND HOPEFULLY THEY HAVE SERVED NINDS VERY WELL OVER THE YEARS. THE OTHER THING WE DO AS THE ONLY ORGANIZATION IN THE FIELD IS TO PROVIDE FEED FUNDING FOR RESEARCH. WE DO RECOGNIZE THAT TOURET'S SYNDROME IS NOT A FIELD TAKEN--THEY ATTRACTS A GREAT DEAL OF RESEARCH FUNDING OR SUPPORT FROM DONORS, FROM GOVERNMENT ORGANIZATIONS SO WHAT WE HAVE DONE OVER THE YEARS ESSENTIALLY TO STEP UP TO THE PLTE AND RAISE AS MUCH MONEY AS WE CAN SO WE CAN SUPPORT RELATIVELY SMALL INNOVATIVE RISKY RESEARCH PROJECT SO THAT INVESTIGATES CAN DO PRELIMINARY STUDIES AND GENERATE PRELIMINARY DATA SO THEY CAN THEN COME TO NIH FOR LARGE ARE FUNDING AND THIS IS SOMETHING THAT I THINK WOOY CAN BE PROUD OF. THIS IS SOMETHING THAT I--I OVER THE YEARS HAVE BENEFITED THE FIELD GREATLY AND I THINK WHEN WE LOOK AT ALL THE RESEARCH THAT HAS BEEN FUNDED BY NINDS AND OTHER INSTITUTES, INTERESTING DISORDERS, I THINK THAT 80% OF THOSE GRANTS WERE FUNDED AT SOME POINT BY THE TOURET ASSOCIATION OF AMERICA. SO THAT IS A HUGE SUCCESS FOR US AND IT REALLY HELPS TO DRIVE SCIENTISTS IN THE FIELD TO GO TO NIH. FOR MORE SIGNIFICANT FUNDING TO CONTINUE THEIR WORKS. THE OTHER THING THAT WE HAVE EMBRACED OVER THE YEARS, IS TO BE MORE INVOLVED IN THE GRANT MAKING PROCESS. WE HAVE HAD ONE OR TWO UR-ONE COOPERATIVE AGREEMENTS OVER THE YEARS IN WHICH NINDS WOULD PROVIDE THE BULK OF THE FUNDING AND WE PROVIDE A SMALL AMOUNT TOWARDS THAT THOSE RESEARCH GRANTS. WE'VE ALSO PLAYED A SIGNIFICANT ROLE IN ADMINISTERING SOME OF THESE GRANTS AND I THINK IF I'M NOT MISTAKEN, THE TOURET'S ASSOCIATION WAS PERHAPS THE FIRST OR ONE OF THE FIRST ORGANIZATIONS THAT DID IN FACT RECEIVE A UR-ONE FROM NINDS, SO WHAT WE'VE DONE IN THAT ROLE IS THAT IS THAT WE PULLED TOGETHER AND--AND THAT GRANT WAS PROVIDED TO OUR ORGANIZATION AND WE SERVE A ROLE OF ALLOCATING FUNDING TO DIFFERENT INSTITUTION SPECIALIZATION OF SPECIFIC ENDOTHELIAL WE TOOK A WAY FROM THE SCIENTIST AND INSTITUTION, THE BUDDEN OF ADMINISTERING THESE GRANTS AND HAVE THEM FOCUS ON THE THINGS THAT THEY DO BEST WHICH IS TO DO THE BENCH SCIENCE, BENCH RESEARCH AND GENERIC RESULTS AND DO PRESENTATIONS AND WE TOOK ON THE BULK OF THAT ADMINISTRATION FOR THAT AND I THINK WE HAVE AGAIN, I THINK WE'VE BEEN RELATIVELY SUCCESSFUL OVER THE YEARS IN BEING A PART OF THOSE KIND OF THING AND I GUESS THINK THAT'S SOMETHING THAT WORKS HAVE V, VERY WELL, AND FINALLY WHAT WE--BEING IN THE POSITION THAT WE ARE, WE'RE PRETTY--VERY CLOSE TO THE SCIENTISTS AND THE CLINICIANS WHO WORK IN THE FIELD. WE'RE IN THE CENTER OF RESEARCH SETTINGS GOING ON IN THE FIELD, SO WE FEEL THAT WE ARE VERY MUCH AWARE AND INFORMED OF THE KIND OF NEEDS AND PROBLEMS THAT EXIST IN THE FIELD THAT WE SUPPORT AND SO WE HAVE TAKEN RESPONSIBILITY TO TRY YOUR BEST TO INFORM NINDS OF LANDSCAPE, OF TOURETTE'S SYNDROME AND THE FIELD AND I HOPE THAT NINDS HAS FOUND THAT TO BE USEFUL OVER THE YEARS SO WE BEING OUTWELL IN THE FIELD, WE'VE EMBRACED THESE DIFFERENT RESPONSIBILITIES AND THESE DIFFERENT ROLES. AND I THINK THAT IS SOMETHING THAT NONPROFIT ORGANIZATIONS LIKE OURS CAN DO VERY WELL AND HELP TO BRIDGE THE GAPS BETWEEN OR THE BETWEEN N INDS AND I THINK IT'S SOMETHING THAT WORKS EXTREMELY WELL. THANK YOU. > THANK YOU DR. Mc NAUGHT, FOR THOSE REMARKS I WOULD NOW LIKE TO INTRODUCE FLORRIAN EICHLER WHO IS OVER THE LEUCODYSTROPHY CLINIC AT MGH. AND WE LOOK FORWARD TO HIS REMARKS WE HAS INTERESTING INSIGHTS ON COLLABORATION AS WELL. >> THANKS, YEAH, SO I--I GUESS I REPRESENT THE CLINICIAN SCIENTIST ON THE PANEL AND I'LL TRY TO NOT TO DUPLICATE TOO MUCH HORMONE AND BRING A DIFFERENT PERSPECTISM MAINFUL SOMEONE WHO M-TEBURKEULOSEIS - -MENTORS INTO THE RARE DISEASE FIELD AND HOW MUCH MENTORING IS IMPORTANT TO THE NEXT GENERATION AS YOU'RE THINK BEING RARE NEUROLOGICAL INDICATIONS THAT MIGHT NOT HAVE A BROAD SCIENTIFIC PLATFORM. IN MY MIND, DEVELOPING STRATEGIES AROUND RARE DISEASES REALLY COMES NATURAL BECAUSE THEY'RE OFTEN STRONG BIOLOGCAL EFFECTS OF SINGLE GENES AND YOU CAN LEVERAGE INTO THE GENE DISCOVERY TO ITS PROOF OF CONCEPT EXPERIMENTS AND THESE CAN REALLY RAPIDLY LEAD TO INSIGHTS AND TRIALS WITHIN A COMMUNITY THAT IS AWIVE VERY MOTIVATED AND ENGAGED AND REALLY MAKING PATIENT RECRUITMENT SO MUCH EASIER THAN THE MORE COMMON DISEASES SO I THINK AS THE FOUNDATIONS OR ADVOCACY ORGANIZATIONS THIS, IS SOMETHING TO TAKE ADVANTAGE OF. JUST MENTION BRIEFLY THREE EXAMPLES THAT I'VE EXPERIENCED IN MY CAREER, HOW INSIGHTS AT THE BENCH LED TO CHANGE AT THE BEDSIDE. SO WE WERE VERY LUCKY A FEW YEARS AGO TO HAVE A VERY ENGAGED FAMILY THAT HELPED US DISCOVERY GENE FOR A HER EDITTERY NEUROPERATING GLOBALLY RAUGHTY AND THEY--THEY WERE SO ENGAGED THAT THEY GAVE SEED FUNDING TO DEVELOP THE FIRST ANIMAL MODAND HE WILL THEN WE GOT A LUCKY BREAK BY UNDERSTANDING THAT THERE WERE SOME TOXIC LIPIDS ACCUMULATING IN THIS ANIMAL AND WE FOUND THEM IN HUMANS, TOO, AND COMING BACK TO THE POINT ABOUT SCIENTIFIC OPPORTUNITIES REALLY COMING OUT OF PLACES YOU DIDN'T EXPECT. I HAD TO LEARN LIPID BIOLOGY AS A NEUROLOGIST AND THE NEXT THING I FOUND OUT IS THAT THESE WERE KNOWN TO ACCUMULATE IN AN ARCTIC CLAM AND NOW I HAD TO LEARN ABOUT MARINE BIOLOGY SO REALLY ONE THING LED TO ANOTHER AND TURNS OUT THAT THESE ARCTIC CLAMS WERE KNOWN TO THE FIELD WHERE THEY WERE USING THIS LIPID TO KILL CANCER CELLS, RIGHT? SO WHAT A GREAT PROOF OF CONCEPT FOR GAIN OF FUNCTION AND FOR TOXICITY. SO WE'VE FIGURED OUT A WAY TO REDUCE THESE LIPITS AND AGAIN FANLY WAS FANTASTIC AND THEY INVITED ME TO A FAMILY REUNION AND THEY MEASURED LIPIDS BEFORE AND AFTER THE BBQ, AND THEN--[LAUGHTER] --AND THEN I GAVE AUGHT THE CANONICAL SUBSTRATE AND FOR 10 WEEKS EVERY LOOKS AT THE AMINO ACID. SO YOU CAN GO QUITE A LONG WAY WITH THIS. WE HAVE AN FDA FUNDED TRIAL AND THAT'S PLACEBO CONTROL, DOUBLE BLINDED INITIAL INVESTMENT OF 50,000 DOCTORS OF THE FAMILY ENDED UP BEING $2 MILLION GRANT FROM FDA, SO GREAT STORY. SECOND STORY JUST ABOUT AGAIN CROSSING DISCIPLINES, FIELD OF DISTRIBUTE ABUSE ABOUT LIPID BIOLOGY, RECENTLY, DISCOVERY THAT ACTUALLY THE VULNERABLE CELL TYPE IS A CELL TYPE IN THE BRAIN CALLED MICRO GHEA THAT ORIGINATES FROM THE BONE MARROW AND WE FIGURED OUT THAT IF WE CORRECTED THAT, THAT BONE MARROW CELL, WE COULD STOP THE DEVASTATING DISEASE AND THIS IS NOW LED TO FIRST GENE THERAPY AND HAPPY TRIAL AND IT'S NOW MULTICENTER AND INCLUDES CENTERS IN THE U.S., BUT ALSO IN EUROPE. AND THIS REALLY ALSO NEEDED INVOLVEMENT OF ANOTHER STAKEHOLDER, MAINLY INDUSTRY, OKAY? SO IT'S IMPORTANT THAT YOU RECOGNIZE THAT AS A RARE DISEASE YOU REALLY ARE A SOUGHT AFTER PARTNER BY MANY START UPS BY MANY INDUSTRY PLAYERS AND THEY'RE WILLING TO ENGAGE IN SOME OF THE BIOLOGY AND THAT RARE DISEASES PRESENT AND THEY NEED YOUR HELP TO UNDERSTAND WHAT THE OUTCOME MEASURES ARE, THAT WILL MAKE A DIFFERENCE. SO, THE THIRD AND LAST POINT, I WANT TO MAKE IS, ABOUT CONSORTIUM BUILDING AND PARTNERSHIPS. SO WE DISCOVERED TWO YEARS AGO THAT THERE WERE NOW TRIALS HAPPENING IN THE THERAPY SPACE, AND THIS RARE LEUCODYSTROPHY THAT ALLOWED FOR THE ORGANIZATIONS TO TALK TO EACH OTHER, SO WHAT WE CREATED WAS A CONSORTIUM THAT ALLOWED SEVEN PATIENT ORGANIZATION TO TALK TO FIVE ACADEMIC CENTERS AND TRY TO BRIDGE THOSE GAPS WHERE--AND AVOID THE SILOS THAT HAD MAYBE BEEN HOLDING THINGS BACK. AND ONE OF THE FIRST THINGS WE SAID IS WE WANT TO ALL-IN CLUESIVE, WE SAID THIS IS NOT JUST THE PHYSICIAN, SCIENTIST VENTURE THIS, IS SOMETHING THAT IS OF INTEREST TO ANYBODY THAT WANTS TO CHANGE OF THE FIELD SO WE INCLUDED PATIENTS AND PATIENT ADVOCATES AND HALF THE PEOPLE IF OUR FIELD ARE BORED AND PATIENT ADVOCATES AND INDUSTRY, AND WE ALSO BROUGHT INDUSTRY TO THE TABLE AS WELL. AND I THINK THIS IS HELPED US REALLY AVOID DUPLICATION OF PAST EFFORTS AND REALLY ALLOW FOR US TO ADDRESS KNOWLEDGE GAPS, TWO THINGS THAT ARE HOLDING US BACK AND MOVING FROM THE BENCH TO THE BEDSIDE. SO WHAT CAN WE LEARN FROM THIS ON AN INTUITIONAL LEVEL. SO I SAY LOOKING AT THE LUCKY BREAKS I'VE HAD IN MY CAREER, I FEEL ONE OF THE BIG THINGS THAT IS--IS PROBABLY MISSING IN A FIELD OF RARE DISORDERS, IS FOSTERING AND THE FIELD HAS CHANGED FROM 10-WENT YEARS AGO AND THE PATIENTS NEED TO HEAR FROM THE PATIENT ADVOCATES THAT THERE'S A NEED AND THEY 92 TO ADDRESS, THERE'S SO SUCH THING AS TOO FEW PATIENTS TO CARE ABOUT THIS AND WE'VE CREATED CENTER FOR DISEASES IN HARVARD IN ORDER TO ALIGN THE BASIC SCIENCE END AND CLINICAL TRIAL END, WE RECOGNIZE FOR MANY COMMON DECS, CLINICAL TRIALS OCCUR BUT IT DOESN'T HAPPEN FOR RARE DISEASES. HOW CAN WE CLOSE THOSE GAPS? NOW CAN WE MAKE THOSE LAPS THAT DON'T KNOW THERE WOULD BE AN OPPORTUNITY TO MOVE THIS FORWARD AND KNOW ABOUT HOW TO RUN A TRIAL. SO, I THINK I TRIED TO ILLUSTRATE THE POINTS THAT CAME UP MULTIPLE TIMES. >> AND THANK YOU SO MUCH FOR DOING SO, SO ELEGANTLY. FLORRIAN AND EMPHASIZING THE IMPORTANCE OF PATIENTS AND PATIENT GROUPS, ONES REPRESENTED HERE TODAY AND THE STAKEHOLDERS AND THE WAY WE CAN COLLABORATE WTH INDUSTRY, GOVERNMENT AGENCIES, AND THE ACADEMIC COMMUNITY. SO THANK YOU FOR THAT. FINALLY OUR FINAL SPEAKER I WOULD LIKE TO INTRODUCE IS DR. LAURA MAMOUNAS, SHE'S ALSO INVOLVED IN THE NIH UNDIAGNOSED DISEASES NETWORK, AND I LEFT OUT PMS, FAILEN MCDERMOTT SYNDROME. SHE'S ALSO WORKING. >> SO THANK YOU ONE OF THE ADVANTAGES OF BEING LAST ON THIS PAN CELL EVERYTHING HAS ALREADY BEEN SAID EITHER BY MY GREAT PANELISTS HERE OR BY WALTER OR PAUL SCOTT SO I'M GOING TO SORT OF HIGHLIGHT THEN, WHAT I SEE IN MY PORTFOLIO AS THE FIVE DEFINING PRINCIPLES FOR ADVANCES DISEASE RESEARCH AND THE FIRST IS THAT WE CAN'T DO IT ALONE. PARTNERSHIPS WITH YOU GUYS, WITH INDUSTRY, WITH THE FDA, WITH OTHER AGENCIES LIKE THE DEPARTMENT OF DEFENSE, AND THAT IS MORE THAN JUST US WRITING CHECKS AND CO FUNDING GRANTS BUT IT REAL LE INVOLVES THE HARD WORK OF UNDERSTANDING EACH OTHER AND TALKING TO EACH OTHER, UNDERSTANDING THE CULTURES THAT YOU KNOW ALLOW YOU TO GET YOUR RESEARCH FUNDED, YOUR BOARDS, YOUR DONORS, FOR YOU TO UNDERSTAND WHAT KEY CAN EASILY DO AND WHAT'S REALLY, REALLY DIFFICULT FOR US TO DO, MORE DIFFICULT. IT INVOLVED TALKING SO THAT WE DON'T DUPLICATE OUR EFFORT, SO THAT WHAT YOU'RE DOING, IS WHAT YOU CAN DO BEST AND EASILY AND WHAT WE CAN DO IS WHAT WE DO BEST AND WE'RE NOT OVER, OVERLAPPING IN WHAT WE DO. YOU KNOW AS PROGRAM DIRECTORS, YOU KNOW WE TRY TO ATTEND YOUR WORKSHOPS. I TRY TO ATTEND AS MANY AS POSSIBLE, TALK TO YOU GUYS, TALK TO THE INVESTIGATORS THAT YOU FUND, WHEN I HAVE A WORKSHOP ON A DISEASE AREA, I ALWAYS TRY TO INVITE YOU, AND INVOLVE YOU GUYS, NOT ONLY INVITE YOU BUT HAVE YOU PART OF THE PLANNING PROCESS AND I FIND THAT REALLY USEFUL AND I ALSO FIND IT ONE OF THE MOST REWARDING ASPECTS OF MY JOB AS A PROGRAM DIRECTOR IS TO WORK WITH YOU GUYS IN THE DISEASE ORGANIZATIONS. THE SECOND IS DEFINING PRINCIPLE IS FUND ONLY THE BEST SCIENCE. THIS IS ACTUALLY VERY, VERY CRITICAL. AND WE NEED TO INSURE THAT RIGOR AND REPRODUCIBILITY IS SECONDINATE TOWER US, THE NIH CAN'T DO IT ALONE. WE HAVE TO HAVE JOURNAL EDITORS, WE HAVE TO HAVE YOU GUYS, WE HAVE TO HAVE INVESTIGATORS, RLY UNDERSTAND THE IMPORTANCE OF CONDUCTING ONLY THE MOST RIGOROUS REPRODUCIBLE WORK. AND I'LL GIVE YOU AN EXAMPLE OF WHERE I'VE PARTNERED WITH THE RETINAL LOCATION'S SYNDROME, AND THE WE HAD A WORKSHOP IN 2011 DEVELOPING, YOU KNOW TALKING ABOUT DISEASE, PRECLINICAL MOUSE MODELS FOR RHETT'S SYNDROME, THE INTERNATIONAL FOUNDATION WAS PART OF THE PLANNING PROCESS. WE PUBLISHED A WHITE PAPER. AND A BIG FOCUS WAS RIGOR AND REPRODUCIBILITY IN OUR MODELS AND THE IRSS HAS ADOPT THAD, IT'S PART OF THEIR FUNDING PROGRAMS AND STEVE MIGHT TALK ABOUT THE ADVANTAGES OF THAT ONE WHEN WE GETS UP IN THE NEXT PANEL. THE OTHER THING IS THAT, YOU KNOW, IT'S--WE ALL HAVE PRESSURES TO FUND CERTAIN RESEARCH CHARITIES BUT IT'S BETTER NOT NOT FUND QUOTE-UNQUOTE BAD SCIENCE AT ALL JUST BECAUSE YOU HAVE PRESSURES TO DO SO. THAT FUNDING BAD SCIENCE CAN ACLLY SET US BACK AND WE ALWAYS WHETHER A TARGET OR A DRUG IS SUCCESSFUL OR NOT, THAT RESEARCH HAS TO PROVIDE A FOUNDATION SO THAT THE NEXT INVESTIGATOR, THE NEXT PROJECT CAN BUILD UPON IT. ALL RIGHT, THE THIRD PRINCIPLE IS OF COURSE FEED THE PIPELINE, WE HAVE TO HAVE PORTFOLIOS AND BASIC CLINICAL AND TRANSLATIONAL RESEARCH. AND AN EXAMPLE IN MY AREA IS THE IMPORTANCE OF BRAIN INITIATIVE. IN TERMS OF BASIC SCIENCE BUT IT'S FUNDING RESEARCH AND UNDERSTANDING BRAIN CIRCUITS, CELL TYPES, DEVELOPING NEW IMAGING TECHNOLOGY, NEW TECHNOLOGIES THAT'S GOING TO REALLY, REALLY BENEFIT A LOT OF THE DEVELOPMENTAL DISORDERS. THE THIRD IS WE TALKED A LOT ABOUT THIS. DISEASES ARE NOT SILOS. AND YET WE--WE EXPECT IN THE CULTURE, WE ALL DO, OF DISEASES AS CLINICAL DIAGNOSTIC CATEGORIZATION, AND WE ALL HAVE OUR--YOU KNOW WE HAVE--YOU KNOW PRESSURES FROM YOU KNOW OUR BOARDS AND WE HAVE PRESSURES FROM HERE AND THERE, BUT WE HAVE TO KEEP TRYING TO BREAK OUT OF THOSE SILOS, AND AN EXAMPLE FROM MY AREA IS, YOU KNOW, WE'RE NOW LEARNING THAT EPILEPSY AND AUTISM AND SCHIZOPHRENIA SHARE A LOT OF THE SAME GENETICS, SHARE A LOT OF PATHWAYS AND YET SCHIZOPHRENIA IS TRADITIONALLY TREATED BY PSYCHIATRISTS AND FUNDED BY THE NIMH AND EPILEPSY IS A NEUROLOGY DISEASE, FUNDED BY NINDS AND SOMEBODY COMES IN WITH AN APPLICATION SAYING I WANT TO STUDY SCHIZOPHRENIA AND EPILEPS SCHEAUTISM AND WE'RE GOING, OH, WHERE DOES THIS BELONG? AND WE HAVE TO MOVE BEYOND THAT, THAT'S CRITICAL AND FINALLY WE HAVE TO INVEST IN THE FUTURE WORKFORCE. WE HAVE TO TRAIN OUR YOUNG SCIENTISTS, WE HAVE TO SUPPORT THEM AND TRAIN THEM IN RIGOROUS GOOD SCIENCE. SO THOSE ARE THE FIVE, I THINK THOSE ARE THE FIVE. THANK YOU. >> GREAT, WELL I WOULD LIKE TO THANK OUR PANEL FOR ALL OF THEIR THOUGHTS AND COMMENTS. AND WE WANTED TO OPEN UP FOR DISCUSSION TO THE GROUP BEFORE WE DO, I JUST WANT TO INVITE YOU LATE THERAPY AND AFTERNOON, THERE WILL BE TWO, ONE HOUR-CONCURRENT WORKSHOPS FROM 1:45-3:45 AND MEMBERS OF OUR PANELS WILL BE BE AVAILABLE IN EACH OF THOSE HOURS TO HAVE ADDITIONAL DIALOGUE AND BRAINSTORM AND TALK BOTHER WAYS WE CAN STIMULATE BASIC RESEARCH. JUST QUICKLY BY A SHOW OF HANDS HOW MANY FOLKS HERE REPRESENT AN ORGANIZATION, A DISEASE ORGANIZATION? AND KEEP YOUR HANDS UP IF YOU FEEL CONFIDENT IN YOUR BASIC SCIENCE RESEARCH. >> OKAY, THAT'S WHAT I SPECTED. SO WE EXPECT TO SEE ALL OF THOSE THAT SEE OUR HANDS RAISE INDEED OUR WORKSHOPS SO WE CAN BRAINSTORM TOGETHER HOW TO MAKE THOSE IMPROVEMENTS AND AS PART OF THE QUESTION AND ANSWER BECAUSE WE WOULD LOVE TO HEAR FROM FOLKS THAT HAVE COME UPON GOOD STRATEGIES OR IDEAS THAT OTHER FOLKS MIGHT HAVE FOR HOW WE CAN IMPROVE THIS AREA. >> HI, PAUL GROSS FROM THE HYDROCEPHALOUS ASSOCIATION, GREATLY APPRECIATE YOUR COMMENTS. SO BEING CURIOUS, I DON'T THINK I HEARD THIS GO THROUGH, BUT IF HAVE YOU A CONDITION WHERE YOU DON'T FEEL LIKE HAVE YOU ENOUGH NEW IDEAS FROM BASIC SCIENCES, THERE'S TWO ISSUES TO ME. THERE'S THE MONEY AND THE PROGRAM THAT YOU PUT TOGETHER BUT PROBABLY THE BIGGER ISSUE IS HOW DO YOU REACH--WHAT MECHANISMS DO YOU HAVE FOR REACHING SCIENTISTS TO HAVE THEM EVEN LIKE READ YOUR RFA, SO LET'S DAY YOU'RE DOING AN INNOVATIVE AWARD FOR THE 25 TO 50 K RANGE, AN ORGANIZATION THAT'S DONE RECENTLY BUT YOU KNOW, IT'S--IT'S COST PROHIBITIVE TO SORT OF MALE TO SOCIETY FOR NEUROSCIENCE, WHAT NOT, I'VE TRIED USING MECHANICAL TURK TO GENERATE, THIS, I'D BE CURIOUS WHAT ARE THE TACTICS YOU FELT ARE BEST FOR GETTING IN FRONT OF A SET OF SCIENTISTS TO BRING NEW IDEAS TO THE TABLE THAT ARE NOT--MAYBE YOUR TRADITIONAL SET OF RESEARCHERS THAT HAVE DEVOTED THEIR CAREERS BUT ARE NOT NECESSARILY, QUITE OUT OF THE BOX OR NEW AND INNOVATIVE. >> YOU'VE ADDRESSED SOMETHING TOTALLY CRITICAL, WE HAVE TO, YOU KNOW THINK OUTSIDE THE BOX. WE HAVE TO GET NEW BLOOD IN. WE DON'T WANT TO BE SO INBRED THAT THE SAME PEOPLE ARE DOING THE SAME THING SO AT NIND S WE'RE THINK BEING THAT IN EVERYTHING THAT WE DO SO IF WE HAVE A WORKSHOP FOREXAMPLE, AND YOU CAN DO THIS TOO, WE SPECIFICALLY TRY TO MAKE SURE WE BRING EXPERTISE AND INVESTIGATORS FROM OUTSIDE THAT DISEASE AREA. TO COME IN, AND GIVE US THEIR INSIGHTS, NOT ONLY DO THEY PROVIDE US WITH A LOT OF GREAT INFORMATION BUT SOMETIMES DURING, THE COURSE OF THE WORKSHOP, NEW COLLABORATIONS GET FORMED. IT'S ABSOLUTELY CRITICAL, THE SECOND IS IN OUR FUNDING ANNOUNCEMENTS, YOU MENTIONED THE SEED GRANTS BUT IN ALL OF OUR FUNDING ANNOUNCEMENTS, WE'RE THINK BEING IN THOSE BULLETS WE WILL SEE IT HOW DO WE BRING IN NEW AREAS THAT ARE REALLY ARE UNDERDEVELOPED AND BRING IN NEW PEOPLE AND THEN ONE MORE TIME WHEN TALKING TO PEOPLE ON THE PHONE AND WE HAVE THE ADVANTAGE THAT I HAVE SEVERAL DISEASES AND I MIGHT BE TALKING TO SOMEBODY IN RHETT'S SYNDROME AND I'LL SAY HEY, YOU SHOULD TALK TO SO AND SO IN TUBE LOW SCLEROSIS AND THEY HAVE A GREAT NEW APPROACH THEY'RE USING SO IT'S ABOUT WORKSHOPS, ABOUT COMMUNICATING, IT'S ABOUT INITIATIVES TO CONSTANTLY TRY TO BRING IN NEW IDEAS AND NEW PEOPLE. >> CAN I SHARPEN THE QUESTION A LITTLE BIT. HAVE YOU THE ADVANTAGE OF HAVING THOSE INITIALS NIH OR NINDS, SO HAVE YOU A PIPE WHEN YOU SPEAK, YOU REMEMBER THE EF HUTON HAT, WHEN YOU SPEAK PEOPLE LYNCH, FOR THOSE WHO HAVE THE BENEFIT AND THE INITIALS. >> I DON'T HAVE A DIRECT ANSWER FOR YOU BUT I WOULD LIKE TO SUGGEST, FLORRIAN AND I WERE TALKING ABOUT IT A BIT THIS MORNING, YOU KNOW WE'RE ALL NONPROFITS ESSENTIALLY SPEAKING TO EACH OTHER AND I THINK ONE OF THE FRUSTRATIONS THAT MANY OF US FEEL IS THAT WE'RE NOT GETTING TO THOSE RESEARCHERS EARLIER IN THEIR CAREER WHEN THEY'RE MAKING THOSE DECISIONS SO PERHAPS A ROLE THAT NINDS COULD CREATE WOULD BE A FORUM THAT THE FOLKS THAT HAVEN'T MADE THAT DECISION YET THAT ARE TRYING TO THINK ABOUT WHAT AREA THEY WANT TO SPECIALIZE IN, GET AN OPPORTUNITY TO INTERACT WITH US AND I THINK FLORRIAN TALKED IN HIS REMARKS ABOUT THE IMPORTANCE OF MENTORSHIP AND HE WAS MENTORED INTO THE RARE DISEASE AND I GUESS THINK CREATING FORUMS WHERE WE CAN ENTICE PEOPLE WITH THE OPPORTUNITIES THAT WE KNOW EXIST BUT WE DON'T HAVE THE OPPORTUNITY TO CONVERSION WITH THEM DIRECTLY. >> AND I'LL ADD ONE PERSPECTIVE FROM ANOTHER PATIENT GROUP, AND THAT IS THAT IT'S A TOUGH PROBLEM, GREAT QUESTION. AND I GUESS I WOULD DIVIDE THE SCIENTISTS HERE AFTER INTO COUPLE DIFFERENT GROUPS. ONE ARE THOSE THAT ARE SOMEWHERE NEAR YOUR FIELD, I MEAN MAYBE THEY PUBLISH AID PAPER 10 YEARS AGO AND THEY LOST THE VISION OR GONE UNDER SOMETHING ELSE. MAYBE THEY'RE TANGENTIALLY INVOLVED? AND THE BOTTOM LINE IS ASSEM BLELLING THE FIELD IS SUCH A POWERFUL TOOL AND IT DOESN'T TAKE A BIG GRANT, CAN YOU DO AN R13 WORKSHOP GRANT THAT WE TALKED ABOUT YESTERDAY. ASSEMBLE ENOUGH RESOURCES ON YOUR OWN AND WITH THE GRAPT TO BRING SCIENTISTS TOGETHER. AND THAT COLLABORATION REALLY BEGINS THERE, THESE PEOPLE CAN BE INSPIRED BY THE GREAT WORK GOING ON BY OTHERS, THERE ARE ALSO WAYS AS LAURA MENTIONED TO INCLUDE PEOPLE THAT ARE TANGENTIAL TO, BUT MORE CENTRAL THAN THEY THINK. LIKE, YOUR DISEASE MIGHT HAVE SYMPTOMS LIKE OURS HAS CARDIOLOGY IS THE BIG KILLER. ALTHOUGH, WE'RE NOT LISTED AS CARDIO LOGICAL DISEASE, AND LISTED IN NEUROLOGICAL DISEASE, SO WHEN HAVE CONFERENCES, WE WILL ALSO HAVE PRACTICE CARDIOLOGIST THAT KNOW SOMETHING ABOUT CARDIO LOGICAL SCIENCE THAT APPLIES TO OUR DISEASE. AND WE REACH OUT TO EXPERT A VAST ARRAY OF FIELDS THAT ARE SOMEWHAT RELATED TO US TO LEARN THE LESSONS AS FAR AS INDICATING SO I THINK A REALLY POWERFUL TOOL IS GETTING PEOPLE TOGETHER IS PAY FOR AN AIRPLANE RIDE OR HOTEL RESERVATION AND THAT'S ALL IT TAKES. >> OKAY, CHRIS, HERE FROM ACADEMY OF NEUROLOGY. --WAIT, WAIT. SO I WILL MENTION THEY HAVE A PROGRAM WHEREBY THEY ADVERTISE FELLOWSHIPS TO PHYSICIANS SCIENTISTS SO THEY HAVE A MENTORING PROGRAM AND THEY--THEY HAVE--MAYBE CHRIS COULD TELL US, THEY HAVE EAR MARKED FELLOWSHIPS AS A GROUP THAT'S LOOKING FOR SOMEBODY IN A RARE DISEASE THEY CAN TALK TO THEM, THEY WOULD ADVERTISE IT AND CO FUND IT. IS THAT ACCURATE. >> YEAH. >> SO IT'S A WAY OF KIND OF MAKE THEY CAN ADVERTISE TO GET THE PHYSICIAN SCIENTISTS, SO, IF I MIGHT JUST ADD TO THAT, THAT IS A GREAT QUESTION, AND IT IS A QUESTION THAT ONE ISSUE THAT WE FACE IN OUR FIELD, AND I THINK A LOT OF FIELDS ESPECIALLY WHERE THE DISORDERS ARE RARE, YOU FACE THAT ISSUE OF HAVING EXPERTS COME INTO THE FIELD. SO WHAT WE HAVE DONE OVER THE YEARS, IS TO CONSITUTE OUR SCIENTIFIC ADVISORY BOARD, SO WE HAVE A BOARD OF SCIENT WHO IS WILL REVIEW GRANT APPLICATIONS AND HELPITOUS CRAFT RESEARCH POLICIES WHAT WE TRY ON TO DO OVER THE YEAR SYSTEM BRING SCIENTISTS FROM DIFFERENT FIELD INTO'S A SCIENTIFIC ADVISORY BOARD. AND A LOT OF THE APPLICATION, GRANT APPLICATIONS WE GET THEY'RE NOT FROM PEOPLE WHO NECESSARILY HAVE EXPERTISE IN THE DISEASE ITSELF BUT RATHER IN THE METHODOLOGIES AND TECHNIQUES AND RESEARCH ITSELF. GENETIC SYSTEM GENETICS AND PEOPLE WERE DOING GENETICS ARE NOT NECESSARILY PEOPLE FROM THAT FIELD. SO WE TRY TO CONCONSTITUTE OR ADVISORY BOARD WITH EXPERTS FROM DIFFERENT PLACES AND BY DOING THAT, THEY HELP TO BRING NEW SCIENTISTS EARLY STAGE SCIENTISTS IN THEIR AREA WORKED PRETTY WELL OVER THE YEARS. >> GOOD MORNING, THANKS SO MUCH FOR A WONDERFUL SET OF DISCUSSIONS SO FAR. I'M ROBERT FROM CHDI, I WANT IT APPLAUD IN PARTICULAR MR. MARGUS'S ARTICULATION, THE WAY I WOULD PUT IT IS HOW TO THREAD THE NEEDLE IF YOU WILL OF TRYING TO ARTICULATE THE SET OF CHALLENGES THAT NEED TO GET RESOLVED WITHOUT TELLING THEM HOW TOICAL CHALLENGE IT. WE STRUGGLE FROM BEING THE DUMB BANK THAT CUTS CHECKS AND SAYS YOU SMART PEOPLE OUT THERE, GO, GO CURE THE DISEASE AND THE OTHER END OF SPECTRUM BEING THE SMARTEST KIDS IN THE WORLD AND SAY, WE HAVE THIS ALL FIGURED OUT AND IT'S YOURS AROUND THE CORNER, WE DON'T WANT TO BE AT EITHER END OF THAT. I THINK IT IS REALLY IMPORTANT T HAVE A LISTING OF ALL THE CHALLENGES THAT ARE STANDING IN YOUR WAY THAT TYPICALLY INVOLVE BASIC RESEARCH. BUT, ARE EVERY BIT AS IMPACTFUL AND POIGNANT AS COMING UP WITH THE COMPOUND ITSELF, AND THANKS TO NANCY WEEKSLER WHO'S HERE, FRANCIS COLLINS AND A LARGE COUPLE OF OTHERS, 22 YEARS AGO, THE GENE THAT UNDERPINNED HUNTINGTON'S PHYSIOLOGY WAS CLONED WE'RE NOW THANKFULLY AT THE PRECIPICE OF CLINICAL TRIALS THAT ARE ABOUT TO GET STARTED, FOR LOWERING THAT PARTICULAR PROTEIN AND WE'RE STILL STRUGGLING WITH THOSE VERY CENTRAL CHALLENGES OF WHERE SHOULD WE BE LOWERING IT AND HOW MUCH TO LOWER IT AND DOES IT NEED TO BE ALLELE SPECIFIC AND EXACTLY WHEN SHOULD WE START TREATMENT AND HOW CAN WE MEASURE THAT TO MAKE SURE WE'RE ACTUALLY LOWERING IT WHERE WE THINK WE LIKE TO LOWER IT IN THE RIGHT CELL TYPES AND I GUESS MAYBE ONE OF THE SORT OF ACTION ITEMS IS TO THINK ABOUT HAVING THIS LAUNDRY LIST FOR EACH ONE OF THE DISEASES WE WORK ON AND SAY THESE ARE THE ISSUES THAT OF COURSE THEY'LL MAKE VERY INTERESTING, HIGH IMPACT PUBLICATIONS, BUT THEN WE'LL BE ABLE TO LEVERAGE THOSE TO BE ABLE TO DRIVE OUR THERAPEUTICS PROGRAMS AND WHAT IT ALSO DOES IS GIVE YOU A REALLY RATIONAL SENSE BASED ON HARD FACTS AND METRICS, AS TO HOW RIPE A DISEASE AREA IS FOR THERAPEUTIC TRANSLATIONAL RESEARCH. I THINK THERE'S A PERVERSE INCENTIVE TO WANT TO JUMP IN THE DEEP END OF THE POOL. WE ALL FEEL THE NEED TO DELIVER HER THERAPY AND HAPPYS AS QUICKLY AS POSSIBLE, WE WANT TO SWING TO THE FENCES AND GET LUCKY BUT AT THE END OF THE DAY, SADLY IT DOESN'T HAPPEN VERY OFTEN SO WE NEED SOME WAY OF ASSESSING WHETHERRER NOT A FIELD IS TRULY RIPE FOR INTERVENTION AND JUST HAVING THE CAUSATIVE GENE OR UNMET MEDICAL NEED OR HAVING PEOPLE YELLING AT THE TOP OF THEIR LUNG SYSTEM NOT THE MED RICK THEY SHOULD BE USING WHETHER SOMETHING IS REALLY READY FOR LIMITING TRANSLATIONAL RESOURCES. NTHIS IS A VERY DIFFERENT TAKE AS IS USUAL OF ME, BUT I HAVE A COUPLE, MR. AND MRS. RODRIGUEZ WHO HAVE BEEN WORKING FOR ME FOR MANY YEARS AND THEY HAVE A DAUGHTER MELANIE AND THEY KNEW THAT MELANIE WOULD COME WITH [INDISCERNIBLE] SOMETIMES AND SHE KNEW ABOUT MY SON JOHN HAVING ATAXIA. WELL SHE STARTED GETTING INTERESTED IN SCIENCE AND HER SCHOOL OUT IN MARYLAND WAS VERY SUPPORTIVE AND THEN MRS. DELGADO GOT A JOB ACROSS THE CALL FROM TRAFFICKING AND I GUESS HIS WIFE, SO THEY BRING MEL AN TOW HER, THEY START HELPING HER WITH HER SCIENCE PROJECTS, THEY WERE VERY UPSET WHEN SHE GOT A B, BY THE WAY, BUT YOU KNOW. BUT SHE IS NOW WORKING AT NIH AND I BELIEVE SHE'S--I THINK SHE'S GOING TO GEORGE TOWN NOW, BUT, MY MESSAGE TO YOU ALL, IS THAT WE HAVE TO TAKE SOME RESPONSIBILITY FOR HELPING REALLY YOUNGER PEOPLE GET INTERESTED IN SCIENCE WITH YOUR LOCAL SCHOOLS, SPECIFICALLY, I THINK WITH MINORITY KIDS. ANOTHER THING I'M WORKING ON IS I'M ON THE BOARD OF Mc CLEANEDON CENTER, WHICH PROVIDES MENTAL HEALTH SERVICES TO THE POOREST OF THE POOR IN THE DISTRICT OF COLUMBIA AND I'VE BEEN WORKING ON THEM TO START AN AFRICAN AMERICAN RESEARCHERS WHO WOULD THEN COME IN BECAUSE WE DON'T HAVE A ENOUGH BLACK PSYCHOLOGISTS, YOU KNOW? SO THERE'S A NUMBER OF THINGS THAT WE ALL CAN DO PERSONALLY AND I WOULD JUST LIKE TO CHALLENGE YOU ALL TO KIND OF AS WE SAY, THINK OUTSIDE THE BOX. WHAT YOU CAN DO. SO THANK YOU ALL. THAT'S ALL. >> I MEAN THAT'S GREAT. I DON'T KNOW IF MICHELLE JONES LONDON IS HERE BECAUSE AT NINDS, SHE'S LEADING AN EFFORT TO DO EXACTLY THAT. GO OUT TO HIGH SCHOOLS, AND THERE'S A BUNCH OF PROGRAM DIRECTORS THAT ARE INVOLVED AND SHE'S GOT A WHOLE COMMUNITY TO GO OUT AND MENTOR AND MEET WITH S, YOU KNOW IN DISADVANTAGED COMMUNITY FOSTER NURSED GET THEM INTERESTED IN SCIENCE. I DON'T KNOW IF ANY OF OUR PROGRAM DIRECTORS ARE HERE THAT HAVE BEEN INVOLVED IN THAT BUT I THINK IT'S REALLYKS SIGHTING AND IT'S BEEN A GREAT PROGRAM. >> HI, MEGAN BRIEWKS I'M REPRESENTING THE MORE THAN BRAIN COALITION. THANK YOU FOR YOUR COMMENTS TODAY. I WANT TO TOUCH ON AND BRING TOGETHER THEMES I'VE BEEN HEARING OVER THE PAST FEW DAYS NOW WHICH IS THE CONCEPT OF ONE BIOMARKERS, AND NOT JUST THE DIAGNOSE OF DISEASE BUT LOOK AT THE PROGRESSION OF THE DISEASE AND LOOK AT THE IMPORTANCE OF REGISTRIES SO I'M THINKING ABOUT THE EMPHASIZE OF BIOMARKERS AND HOW MUCH YOUR ENTITIES YOUR ORGANIZATION PUTS ON DISCOVERYING AND IDENTIFYING THIS NEW BIOMARKERS TO OVERCOME SOME OF OUR REGULATORY HURDLES FOR HOW WE CAN IMPROVE AND GET THINGS THROUGH TO MARKET AND I'M THINKING NOT JUST ABOUT THE TREMENDOUS EFFORTS THAT ARE PUT INTO THE BRAIN INITIATIVE BUT NOW THAT WE HAVE THE MEDICINE INITIATIVE AND WHAT ARE SOME OF THE EFFORTS THAT ARE GOING ON TO TRY AND BRING THOSE TWO EFFORTS TOGETHER, I KNOW IT'S STILL REALLY EARLY BUT HOW ARE INDIVIDUAL INSTITUTES LIKE NINDS, THINKING ABOUT HOW THESE TWO MAJOR EFFORTS WILL COME TOGETHER TO INFORM, PARTICULARLY SOME OF THE DISEASES THAT DON'T HAVE THE BIOLOGY WELL UNDERSTOOD. >> SO I CAN SPEAK FROM PATIENT ADVOCACY PERSPECTIVE, ONE THING WE'VE BEEN INTERESTED IN IS ACADEMICS SEEM TO HIT A ROAD BLOCK ONCE THEY GET INTO THE REGULATORY PIECE OF BIOMARKERS, THEY DEVELOP THE DATA AND A NUMBER OF GROUPS ARE USING MEASURES IN CLINICAL TRIALS IN OUR DISEASE THAT WE THINK COULD BE PUSHED VERY EASILY ACTUALLY TOWARD BIOMARKER QUALIFICATION SO WE'VE BEEN TRYING TO WORK WITH THEM TO BRING IN CONSULT CULT ANTS WITH THE EXPERIENCE IN FDA AND CONNECT THEM WITH THAT KIND OF EXPERTISE BECAUSE QUITE FRANKLY, I MEAN, I'VE BEEN IN EACH OF THESE PLACES ACADEMICS AND MLH ADVOCABULARY KASP A R SCHEA LOT OF ACADEMICS DON'T HAVE THE TIME TO JUMP IN AND UNDERSTAND THAT. SO WE TRY TO FACILITATE THAT. THE LITTLER THING I WAS JUST TALKING WITH RON EARLIER THAT WE--WE'VE LAUNCHED A CONSORTIUM WITH A CRITICAL PATH INSTITUTE AND CRITICAL PATH IS A NONPROFIT, THEY WERE FORMED IN CONJUNCTION WITH FDA AND AND THEY DO A LOT WITH TRYING TO AGGREGATE DAT AND MOVE FORWARD BIOMARKER QUALIFICATIONS. SO I THINK THAT'S ANOTHER PATH. BUT IF I CAN JUST GO BACK TO THE NIH STRATEGIC PLAN AND JUST UNDERLINE ONE THING REALLY STRONGLY. IS TO GET TO QUALIFIED BIOMARKERS, WE ALL HAVE THE SHARING ISSUE, WITH THE DATA SHARING ISSUE AND I ALMOST WISH THERE WAS MORE TEETH AND THE NIH GRANT REQUIREMENT FOR DATA SHARING THAN THERE IS, BECAUSA'S ONE THING WE ENCOUNTER WITH OUR EFFORT TO TRY TO PUSH THIS DATA AGGREGATION MODEL WITH THE PATH INSTITUTE IS THAT TRYING TO GET PEOPLE TO SHARE DATA HAS BEEN REALLY, REALLY TOUGH. SO JUST, YOU KNOW CIRCLING BACK TO YOUR QUESTION, I THINK, AS PATIENT ADVOCACY GROUPS LEARNING ABOUT THE PROCESS, ABOUT WHAT IT TAKES TO GET BIOMARKERS QUALIFIED AND MAYBE EVEN MORE IMPORTANTLY, FINDING OUT WHO KEY CONSULTANTS ARE THAT CAN YOU BRING IN AND HELP PEOPLE DO THIS. I THINK IS AN IMPORTANT WAY YOU CAN FACILITATE. WE'RE WORKING WITH THREE DIFFERENT GROUPS RIGHT NOW THAT WE'VE CONNECTED WITH EXPERT REGULATORY EXPERTS TO TRY TO HELP THEM WITH THREE DIFFERENT BIOMARKERS. >> YEAH, SO AT NINDS, BIOMARKER DISCOVERY AND DEVELOPMENT ARE A REALLY, REALLY STRONG FOCUS IN OUR DISEASE PORTFOLIOS AND I'M THINKING OF JUST A FEW EXAMPLES, SO FOR PARKINSON'S DISEASE, WE HAVE A PD BIOMARKERS INITIATIVE, PROGRAM, AND IT'S SORT OF, YOU KNOW KIND OF GOT STARTED TO SEE HOW WE COULD ACTUALLY, YOU KNOW HAVE THAT PROCESS WOULD WORK OUT AND AS WE LEARN FROM THAT WE LEARN ABOUT OTHER DISEASES. AND WE ALSO AS MENTIONED EARLIER WE HAD REALLY--WE HEAVILY PARTICIPATE AND ARE INVOLVED IN THE RARE DISEASES CLINICAL RESEARCH NETWORK. WE'RE FUNDING SOMETHING LIKE 14 U54S AND THAT PROGRAM AND A BIG COMPONENT OF THAT PROGRAM IS BIOMARKER DEVELOPMENT I KNOW A COUPLE DISEASES THAT I'M INVOLVED IN AND THE RHETT'S INCHROME INITIATIVE INCLUDE A HEAVY DOSE OF BIOMARKER DEVELOPMENT. THIRD WE HAVE OUR NEURONEXT PROGRAM, I THINK ELIZABETH McNEAL WILL TALK ABOUT THAT IN THE THIRD PAN AND HE WILL THAT THAT'S REALLY DESIGNED FOR CLINICAL TRIALS AND THERE'S A STRONG BIOMARKER DEVELOPMENT PROGRAM OR COMPONENT TO THAT. AND FOURTH AND I THINK I CAN TALK ABOUT THIS BECAUSE IT WENT THROUGH OPEN SESSION OF COUNCIL MY COLLEAGUE GLEN KNUCKLES AND DEVELOPING A NEW INITIATIVE THAT WILL COME OUT ANYTIME THAT IS SPECIFICALLY DESIGNED FOR CLINICAL TRIAL READINESS AND I THINK YOU CAN LOOK AT THE NOTES FROM OPEN COUNCIL, THAT SHOULD COME OUT ANYTIME AND A BIG COMPONENT OF THAT IS BIOMARKER DEVELOPMENT. I DON'T KNOW IF YOU WANT TO SAY ANYTHING ABOUT THAT, BUT--I'M SURE THERE ARE OTHER PROGRAMS THAT ARE THINKING ABOUT, AND THE CRITICAL PIECE OF BIOMARKER DEVELOPMENT. >> I WOULD LIKE TO ADD JUST ONE THING ABOUT THIS VERY IMPORTANT ASPECT OF BIOMARKERS AND THAT IS THAT ALL OF US ARE LOOKING FOR THEM. VERY FEW OF US HAVE THEM AND MANY OF US BELIEVE WE WON'T REALLY HAVE A VALIDATED BIOMARKER UNTIL WE HAVE OUR FIRST TREATMENT BECAUSE YOU KNOW HOW DO YOU KNOW THE DIFFERENCE BETWEEN AN ANOMALY AND YOU KNOW, THIS PECULIAR TO THIS ONE PATIENT VERSES SOMETHING THAT'S REALLY GOING TO BE A BIOMARKER FOR YOUR WHOLE DISEASE UNTIL HAVE YOU THAT FIRST TREATMENT AND CAN YOU SAY THIS BIOMARKER WENT UP WITH THIS EFFECTIVE TREATMENT. BUT SECONDLY BIOMARKER ARE NOT JUST IMPORTANT TO BIOMARKER ASPECTS THEY'RE EARLY STAGES OF IDENTIFYING A PROMISING DRUG, WELL THIS LOOKS GOOD BECAUSE IT RAISED THE VALIDATED BIOMARKER SO LET'S DEVELOP THIS DRUG. SO TERRIBLY IMPORTANT QUESTION. I WISH ALL OF US HAD THEM. BUT VERY FEW OF US DO. WE'RE ABOUT TO HAVE OUR THIRD BIOMARKER MEETING AND THIS IS A GOOD ANSWER TO PAUL GROSS' QUESTION ABOUT HOW TO PULL NEW PEOPLE IN. WE'RE INVITING PEOPLE TO THIS THIRD BIOMARKER MEETING WHO HAVE BIOMARKERS OR ARE ON THE CASE AND OTHER DISEASES TOTALLY. WE WANT TO LEARN FROM EVERYBODY IN THAT REGARD. >> SO, RON THAT ADDRESSES AN ISSUE THAT BRAD BROUGHT UP ABOUT MOUSE MODELS NOT MIRRORING THE DISEASE. SO IF YOU WORK TOWARD DEVELOPING BIOMARKERS FOR TARGET ENGAGEMENT IN MODULATION IN THE MOUSE MODEL. IT ALMOST DOESN'T MATTER IF THE--BECAUSE THE MOUSE IS NOT GOING TO HAVE THE DISEASE. I THINK WE ACCEPT THAT IT'S NOT GOING TO RECAPITULATE, THE HUMAN DISEASE AND THEY DON'T EVEN ACTUALLY HAVE THE PHENOTYPE. IF YOU CAN--IF YOU HAVE BIOMARKERS IN THE MOUSE MODEL THAT CAN SHOW TARGET ENGAGEMENT AND MODULATION, THAT ALONE MAY BE ENOUGH EVIDENCE TO THEN GO TO YOUR CLINICAL TRIAL AS FAR AS EFFICACY AND THAT WOULD INTEREST THAT. >> YOU HAVE TO CLARIFY A BIT TOO, SO THERE ARE REGULATORY REASONS AND A LOT OF BUSINESS REASONS AND RISK MITIGATING REASONS WHY YOU LIKE TO HAVE BIOMARKERS, TOO, SO HAVE YOU BIOMARKERS THAT WERE JUST MENTIONED WHERE YOU HAVE A PET OR SOMETHING THAT WILL SHOW UP ON A SCAN SO THAT THEY SHOW THAT THE DRUG GOT TO THE BRAIN AND ENGAGING WITH THE PROTEIN IT'S ENGAGING WITH AND THAT MAKES EVERYONE FEEL MORE CONFIDENT THAT AT LEAST IF IT DOESN'T WORK, IT'S NOT BECAUSE IT DIDN'T GET TO THE BRAIN, IT'S AN IMPORTANT TOOL AND IF YOU HAVE THAT, THEY ARE MORE LIKELY TO PICK YOUR DISEASE OVER SOMEONE ELSE'S. THERE'S ALSO THOUGH, A DESIRE, MAYBE THERE'S A BIOMARKER THAT SAYS WHETHER THERE'S SICKNESS HERE OR NOT SO THE CASE OF TOO MANY LIPIDS, AND YOU KNOW THOSE LIPIDS CAUSE PROBLEMS, IN WHAT WAS IT CLAMS OR SOME OTHER KIND OF DISEASE, THEN MAYBE LOWERING THOSE LIP ID IS A GOOD BIOMARKER AND TO WAIT OUT AROUND AND SEE IF THE PATIENT GETS BETTER IF IT'S A DISEASE, MIGHT HAVE TO WAIT A DECADE OR SOMETHING, SO THAT WOULD MAKE THINGS BETTER BUT THIS CHALLENGE OF FINDING SOMETHING THAT YOU GET A READ OUT FOR, FOR CHANGES TOGETHER WITH THE CLINICAL PRESENTATION OVER TIME, WE ALL GET IT BUT, I DO HAVE TO CHIME IN THAT SUCCESS WE'VE HAD IS PRETTY PATHETIC TO DATE. PEOPLE HAVE SUBMITTED EVEN TO MY ORGANIZATION OVER 37 BILLION GRANT APPLICATIONS JUST ON HOW TO USE MASS SPEC OR TRANSCRIPTION PROFILING OR SOMETHING CONVINCED THEY'RE GOING TO FIND A BIOMARKER AND IT'S NEVER GOOD ENOUGH RESPONSE AND WE NEVER GET THERE SO I WANT TO SAY, WE ALL GET THAT, WE REALLY, REALLY NEED THEM BUT MAYBE IN THE--BESIDES JUST LOTS OF PEOPLE TO LOOK FOR THEM WE COULD REALLY USE TECHNOLOGY THAT HAVE A NEW SHOT AT IT. >> AND WHEN YOU SAY NOT GOOD EH SCIENCE, YOU MEAN LIKE UNDERPOWERED STUDIES OR-- >> YOU DON'T KNOW IT'S ASSOCIATION OR CAUSAL EFFECT. IT ALSO JUST POWERED ENOUGH OR YOU KNOW RISING ABOVE, I MEAN, YOU'LL GET ANSWERS BACK WHERE THERE'S NOT STATISTICAL SIGNIFICANCE BUT IT'S TRENDING OR SOMETHING. >> OR IS IT INFORMATIVE. SO I WANT TO FOLLOW UP ON SOMETHING THAT JOHN SAID ABOUT THE ANIMAL MODELS IN THE NEURODEVELOPMENTAL DISORDERS FIELD, WE'RE REALLY RECOGNIZING THE IMPORTANCE OF REVERSE TRANSLATION, SO FROM BIOMARKERS DEVELOPED INICALLY, I'LL GIVE YOU AN EXAMPLE, AUDITORY POTENTIALS WHICH MEASURE BRAIN CIRCUIT FUNCTIONS AND YOU CAN DEVELOP THOSE CLINICALLY AND IF YOUR PATIENT POPULATION HAS THAT, A DEFICIT IN THAT THEN GO BACK TO YOUR MOUSE MODAND HE WILLEE IF IT REVERSE TRANSLATE ITS, AND TRYING TO FORWARD TRANSLATE F. IT DOES REVERSE TRANSLATE, THEN IN THE MOUSE MODEL YOU CAN DO ALL KINDS OF THINGS TO UNDERSTAND THE BIOLOGY AND THEN GO BACK TO THE CLINIC TO SEE WHETHER IT HOLDS UP AND YOU GO BACK AND FORTH AND BACK AND FORTH. AND THIS IS REALLY A NEW WAY OF USING MOUSE MODELS, SO THAT WE MAY NOT BE ABLE TO MODEL CIRCUIT DISFUNCTIONS, WE REQUEST BACK TO THE MOUSE OR SEE IT IN THE MOUSE, THAT COULD BE A PHARMACODYNAMIC MARKER FOR WHEN WE GIVE A DRUG, ARE WE IMPROVE TAG PARTICULAR MARKER? >> ONE QUICK POINT ON SHARING AND I THINK THAT CAME UP AND I FEEL AS A CLINICIAN AND ACADEMIC I'M A GOOD PERSON TO ADDRESS THAT. ONE WAY WE TRY TO DO THIS, SO WHEN WE BUILT CONSORTIUM ACROSS DIFFERENT ACADEMIC CENTERS WE'VE ACTUALLY ESTABLISHED BANK ACCOUNTS OUTSIDE OF INSTITUTIONS. IF YOU DIDN'T WANT TO SHARE, WE SAID OKAY, DON'T HAIR SHARE, LET'S HAVE A BIOREPOSITORY, JUST LET US KNOW WHERE SAMPLES ARE, SO WE TAKE FIRST STEPS IN PARTICULAR DIRECTIONS. WE DON'T HAVE TO NECESSARILY GO ALL THE WAY, AND I THINK FOR INSTANCE INFORMED CONSENT IS VERY IMPORTANT, WHAT DO PATIENTS ACTUALLY CONSENT TO, DOES THE LANGUAGE SAY SHARING IS POSSIBLE, OFTEN PIs WANT TO SHARE BUT THEN INFORM CONSENT AND THIS DRIVER OR THIS DISEASE AND YOU WANT TO SHARE MAYBE WITH TACKERIN SON'S OR OTHER FIELDS, YOU CAN'T DO IT, SO IT'S WORTH STRATEGIZING AROUND SORT OF THE INFRASTRUCTURE AS YOU THINK ABOUT BIOMARKERS. >> AND WALTER, HAS A QUESTION TO RAISE WITH YOU OR DEDUCING? >> SO GOING BACK A WAYS TO THE COMEBTS THAT ROBERT AND BRAD MADE. WHEN WE DID. STRATEGIC PLAN AND DISEASES, THERE WAS A CALL THAT WE SHOULD REARRANGE HOW WE THINK ABOUT OUR DISEASES AND PUT THEM ON KIND OF A LANDSCAPE, KIND OF LIKE ROB AND BRAD MENTIONED WHERE EACH DISEASE WOULD INDICATE WHAT THEY KNOW, WHAT THEIR BARRIERS ARE, AND WE NEVER REALLY GOT AROUND TO DOING IT. IT'S NOT SOMETHING I THINK NINDS COULD TACKLE ON THE INSIDE OR SHOULD TACKLEOT INSIDE, BUT IT WOULD BE VERY INTRIGUED BY THE QUESTION OF WHETHER OR NOT, THAT COULD BE A JOINT PROJECT, WITH THE DISEASE ORGANIZATIONS WHERE YOU'RE A SCIENTIFIC ADVISORY BOARDS COULD WORK MAYBE WITH US, WE DEVELOP A TEMPLATE, AND THEN, ALL THE ORGANIZATIONS COULD THEN SEE WHAT EVERYBODY ELSE IS STUMBLING BLOCKS ARE, TOO, AND MAYBE SEE CROSS TALK. BECAUSE I THINK THAT WAS THE MAIN TAKE HOME POINT FROM THE DISEASE GROUP THAT TRANSLATIONAL RESEARCH TEGGIC PLANNING WAS THAT THERE'S A LOT OF CROSS TALK IN OUR DISEASES. IT'S NOT HAPPENING AND THAT MAY BE NINDS SHOULD FACILITATE IT. SO I'M INTERESTED IF PEOPLE HAVE IDEAS ABOUT HOW THAT MIGHT HAPPEN OR WHETHER IT'S WORTH DOING. >> MAYBE ONE FINAL COMMENT OR QUESTION? >> THANK YOU, VERY FOCUS FON, SO YOU MENTIONED A NICE CONVERSATION PIECE, THE ROLE OF THE EXECUTIVE FOR THE ORGANIZATION AND THE SCIENCE OF THE DISEASES AS A PROGRAM LEADERSHIP, I WANT TO TURN THAT BACK A LITTLE BIT, WE'VE HAD A LOT OF DISCUSSION ABOUT WHAT TO DO WITH OUR RESOURCES BUT KNOW WE ALL HAVE LIMITED RESOURCES ARE ON SOME LEVEL, SO FOR A GROUP OF PANELISTS IF WE COULD GO THROUGH A COUPLE OF PANELISTS THE IDEA OF WHAT'S NEW IN COMMUNICATING THE VALUE OF BASIC SCIENTISTS TO OUR DONORS TO THE PEOPLE WHO ULTIMATELY SUPPORT OUR ORGANIZATION? HOW DO WE MAKE SURE THAT THEY GRASP WHAT'S GOING ON, WHY IT'S IMPORTANT, HOW IT WORKS, THAT REVERSE TRANSLATION BACKWARDS, HAVE YOU HAD ANY INCIDENT THIS YEAR THAT ARE NOVEL OR THAT ARE SURPRISING IN YOUR OWN SCIENTIFIC COMMUNICATION. >> I'LL START OFF WITH A THEME AND THEN THEY'LL TELL YOU A BET WARE TO DO IT. MY THEME HAS BEEN TO TREAT DONORS AS INVESTORS SO BEFORE MY KIDS WERE DIAGNOSED AND I DIDN'T CARE ABOUT RAISING MONEY BUT I DONATED $20 IN RESPONSE TO A DIRECT MAIL PIECE ALL IT EVER GUARANTEED ME IT THAT I WOULD GET A LOT MORE DIRECT MAIL PIECES FROM THEM EVERY MONTH SO I'VE BEEN TRYING TO DO ALWAYS DO IT THE OTHER WAY AND SAY EVEN IF YOU GAVE A DOLLAR, HERE'S HOW YOUR DOLLAR MADE A DIFFERENCE AND NOT BURIED THEM IN THIS INFORMATION BUT REALLY MAKE IT CLEAR THAT WE ARE STRETCHING THE DOLLAR MORE THAN PEOPLE DO OR SMARTER ABOUT IT, ON OR WHATEVER. AND TRY TO MAKE THEM PART OF THE EFFORT. SO A LOT OF OUR DONORS DON'T SEEM TO HAVE THE APPETITE TO KNOW THE SCIENCE THAT I'M DIEING TO TELL THEM ABOUT BUT ON THE OTHER HAND, IF THEY WANTED TO KNOW, WE COULD GIVE THEM A SIX HOUR PHONE CALL TO FILL THEM IN ON EVERYTHING. THERE'S NOTHING--YOU KNOW THIS IS REALLY, REALLY IMPORTANT TO US AND WE WOULD LOVE TO SHARE WITH YOU, IF YOU WANT TO KNOW AND I THINK JUST CONVEYING THAT GETS YOU TREMENDOUS SUPPORT. THERE'S ALSO CERTAIN THINGS THAT WE ALL KNOW THERE ARE THESE TRENDS THAT COME ALONG THAT ARE GREAT FOR RAISING MONEY AND THEY'RE DANGEROUS TRAPS, TOO FOR EXAMPLE, WHEN STEM CELLS FIRST CAME OUT, MAYBE IT WAS REALLY, REALLY EARLY DAYS FROM EVAMPLEG LIFTS AND MAKING BIG DEALS ABOUT IT ABOUT ON THE OTHER HAND TWAS IN THE NEWS ALL THE TIME IF PEOPLE COULD GET IT AND THE PUBLIC, YOU KNOW, YOU TAKE A DISEASE WITH CELLS DISAPPEARING AND YOU PUT NEW CELLS IN AND THEY START WIRING RIGHT AND DOG THE RIGHT THING AND YOU CARRY THE DISEASE, SO NEXT THING YOU KNOW, FAMILIES THAT ARE RAISING MONEY, THEY WOULD SAY ARE WE DOG ANYTHING WITH STEM CELLS AND WE WOULD LOVE TO TELL OUR DONORS WE ARE DOING THINGS WITH STEM CELLS AND IF I WRITE ONE GRANT, KIMAKE A BIG DEAL OUT OF IT AND THAT HAPPENS EVERY YEAR AND WE HAVE IPS CELLS FROM OUR PATIENT'S OR WE HAVE TO ALL SEQUENCE ALL THEIR GENOMES OR WHATEVER. SO THERE IS A LITTLE BIT OF THAT. BUT THERE'S A LOT TO BE LEARNED FROM THAT AND YOU HAVE TO DISTILL SCIENCE DOWN TO PARTICULAR THINGS LIKE RIGHT NOW WE ARE SEQUENCING A BUNCH OF GENOMES AND LAST YEAR WE MOUNTED A CAMPAIGN TO OUR--KIND OF OUR BOAST DONORS AND EXPLAINED THAT YOU KNOW SEQUENCING COSTS HAVE DROPPED DRAMATY AND THERE'S THIS NEW DAY AND GENETICS WE THINK THERE ARE MODIFIER GENES BECAUSE WE SEE KIDS WITH THE SAME GENES SCREWED UP FOR A LOT OF VARIABILITY SO WE WOULD LIKE TO SEQUENCE GENOMES AND IT COSTS 1500 TO $2000 PER GENOME. COULD YOU SUPPORT KIDS AND PEOPLE WOULD SAY, YOU KNOW I'LL DO FIVE KIDS AND SUPPORT THEM OR WHATEVER. SO THERE ARE WAYS TO THINK ABOUT THE SCIENCE AND IN A WAY THAT PEOPLE CONNECT WITH IT AND AGAIN, MAYBE IT'S BECAUSE I'M A BUSINESS PERSON BUT I REFER TO AND JOINING EFFORTS AND IT'S NOT BECAUSE WE'RE HITTING UP ON YOU BECAUSE THIS A SAD DISEASE OR SOMETHING LIKE THAT. DOES THAT HELP AT ALL? >> SO WE'VE ACTUALLY SET A BAD PRECEDENT FOR THE DAY. WE ARE WELL OVER OUR TIME BUT EVERYBODY WILL AGREE IT WAS A WORTH WHILE CONVERSATION. I WANT TO THANK AGAIN OUR PANELISTS THIS MORNING FOR SUCH INVITEFUL COMMENTS. [ APPLAUSE ] --INSIGHTFUL COMMENTS [ APPLAUSE ] AND RESITTITY WAYOU CAN JOIN US FOR THE BREAK OUT SESSIONS WHERE WE CAN CONTINUE TO CONVERSATION. >> SO THIS WILL A--BITS I SHORT BREAK SO FIVE MINUTES AND BACK. GET TO WORK. >> THE LAST ONE WAS MORE BASIC RESEARCH AND AS OUR MODERATORS WE HAVE. >> AND FROM THE INTERNATIONAL FOUNDATION AND ROBERT HUNTINGTON'S FANNATION AND SHANKER FROM AFT RAZENNICCA AND AND THE DEVELOPMENT, OKAY, GREAT. >> SO JUST QUICK WELCOME, THE SLIDE FOR TRANSLATIONAL RESEARCH, I'M NOT THE ONLY ONE FROM OUR OFFICE, I'M JOINED BY SEVERAL PROGRAM DIRECTORS JUST A QUICK INTRODUCTION IF YOU COULD TURN AROUND AND SEE HER, CHUCK MANAGES OUR SMALL MOLECULE PROJECTS AND MANY THAT WE HAVE IN PLACE, I SAW PASCAL, HANG WHO'S PART OF THE PLURIBU PRINT OF THE THERAPIES NETWORK AND ALSO CHRIS IS, SO CHRIS IS OVER THERE, HE WORKS WITH HOW AND MANAGES THE LARGE MOLECULES PEPTIDES AND BI-THERAPEUTICS SO I INVITE TO YOU COME AND TALK TO US, AND WE'RE FAIRLY NEW TO THE OFFICE, AND WE ARE PRETTY WELL INTEGRATED, WITH ALL THE INSTITUTES, MANY OF OUR PROGRAM DIRECTORS, WE WORK WITH DIRECTLY FORMANY OF OUR PROJECTS, A LOT OF THEM KNOW ALL ABOUT US SO HOPE LOOFULY WE CAN SPREAD THE WORD AND WE ALSO HAVE A BREAK OUT SESSION, TO TALK ABOUT SOME OF OUR PROGRAMS FOR TRANSLATIONAL RESEARCH, MANY OF OUR PANELISTS HERE ARE INVITED TO JOIN US AND VICON FIRMATION FROMMATE LEAST TWO OF THEM THAT THEY WILL JOIN US SO IT SHOULD BE QUITE INTERESTING TOPICS THIS AFTERNOON, SO IF YOU HAVE TIME PLEASE JOIN US. SO WE WANT TO MAKE THIS AN INTERACTIVE SESSION, WITH QUESTIONS AND SO ON AND O FORTH SO WE THOUGHT WE WOULD KEEP THE INTRODUCTIONS TO VERY MINIMUM. OLISTS WILL HAVE FIVE MINUTES TO INTRODUCE THE ORGANIZATION AND TOPICS THEY ARE PASSIONATE ABOUT AND COMMON EIGHTY VIS IDENTIFIED AMONG OUR PANELISTS AND HOPEFULLY THAT WILL DRIVE OUR DISCUSSION LATER ON AND THE DISCUSSIONS WE WILL HAVE BUT BEFORE WE JUMP INTO THIS I HAVE TWO QUESTIONS I WOULD LIKE TO SEE A SHOW OF HANDS FOR SO THE FIRST ONE IS HOW MANY PEOPLE HERE FROM THE ACADEMIC SIDE OF TRANSLATION. HOW MANY ARE FROM NONPROFITS? A VERY LARGE MAJORITY HERE AND HOW MANY FOR PROFIT INDUSTRY WE HAVE THREE, THAT'S GOOD. SO HOW MANY OF YOU ENGAGED IN PRECLINICAL ACTIVITIES. HOW MANY ARE ENGAGED IN CLINICAL ACTIVITIES, ALMOST A THROW AWAYY QUESTION I SHOULD HAVE ASKED THE ORGANIZER OF THIS HOW CLINICAL AND PRECLINICAL TO BE CONNECTED AND MOST OF YOU HAD TO THINK TWICE ABOUT THIS WHETHER YOU'RE EXCLUES OFLY CLINICAL OR PRECLINICAL AND THAT REALLY DRIVES SOME OF OUR CHALLENGES WITHIN OUR INSTITUTE, TOO, AND WE THEREFORE WORK CLOSELY WITH OUR RESEARCH COLLEAGUES TO MAKE SURE WE REALLY UNDERSTAND THE LANDSCAPE AND HOW WE FUND THINGS AND HOW WE PRIMATES ORIGINALITIZE OUR ACTIVITIES WITHIN OUR INSTITUTE. SO AS A WAY OF DESIGNING WHAT WE WILL DISCUSS OVER THE NUMBERS 55 MINUTES WE THOUGHT THAT TRANSLATIONAL RESEARCH IN THIS SCOPE HAS TO BE LITTLE BIT BETTER DEFINED BECAUSE OF THIS, SO BECAUSE SO WE THOUGHT THORS OUR CONVERSATION OUR DISCUSSION WILL BE CLOSE TO PHASE ONE AND PHASE TWO CLINICAL STUDIES AND THAT'S THE LANDSCAPE WE WOULD COVER AND THAT FITS QUITE WELL WITH THE FOLLOW ON PANEL WHICH IS A CLINICAL PANEL WHICH THEN LEADS TO OUR BREAK OUT SESSIONS SO HOPEFULLY THIS IS A PROGRESSIVE TRANSITION BETWEEN BASIC RESEARCH AND BASIC RESEARCH TRANSLATION AND CLINICAL AND WE WILL HAVE ALL SORTS OF REALLY GOOD QUESTIONS AND DISCUSSIONS AT OUR BREAK OUT SESSION. SO JUST TO GET STARTED. PERHAPS SUSAN DICKEN SON WILL GET TO THE PODIUM AND WE CAN GO FROM THERE. >> THANK YOU TAMIR, I AM SUSAN DICKINSON, I'M WITH THE ASSOCIATION OF FRONT O TEMPERRAL HEALTH. SORRY ABOUT THAT, I HAVE BAD HANDS. REALLY BRIEFLY, AFTD WORKS ON FRONTAL TEMPORAL, AND 60,000 PEOPLE IN THE U.S. LIKE MOST OF YOU HERE, GET THE SHOW OF HANDS, WE HAVE A BROAD MISSION SPANNING RESEARCH SUPPORT EDUCATION AND AWARENESS AND ADRO VOCABULARY KASP A R SCHELIKE MOST OF YOU HERE FROM TALKING TO YOU OVER THE PAST 24 HOURS WE SEE OUR MAIN GOAL AS BUILDING A COMMUNITY. >> WE'LL BE PULL NOTHING THE SAME DIRECTION, WE'REAVE FAIRLY YOUNG ORGANIZATION, WE'RE JUST HITTING 13 YEARS OLD, AND SO MY PERSPECTIVE ON THIS PANEL WAS REALLY AND WE KNOW THAT'S WHAT MOTIVATES THE DONORS AND THE PTS BUT DOES THAT ACTUALLY MEAN AS A YOUNG NONPROFIT. ALL WE KNOW IN THE BEGINNING IS THAT WE HAD LIMITED FUNDING AND LIMITED STAFF. >> WE CERTAINLY CAN'T CONTROL THE SCIENCE AND WE KNEW WE COULDN'T FIT THE BILL ALONE. BUT WE DID IDENTIFY PRETTY SOON THERE ARE THINGS THAT WE'RE GOOD @ THE CENTER OF THAT HUB I'M TRYING TO BUILD THIS COMMUNITY. SO WE THAN WE MEET, REACH OUT AND MEET ALL THE PEOPLE IN THOSE DIFFERENT SECTORS. WE CAN INTRODUCE THEM TO EACH OTHER, FACILITATE COMMUNICATIONS AND WE CAN ENCOURAGE THEM TO WORK TOGETHER AND COLLABORATE. WE CAN PROVIDE SEED FUND NOTHING THE PAST PANEL RATHER EXTENSIVELY AND I THINK AWLESS WE NEED TO REMEMBER THAT OUR SEAT AT THE TABLE AND CRITICAL WE KEEP THE FOCUS ON THE PATIENTS AND NO MATTER WHAT'S GOING ON, THAT YOU DO JUST REMIND EVERYBODY WHY WE'RE ALL HERE AND WHAT THE BOTTOM LINE GOAL IS. SO WITH THAT IN MIND, WE HAVE, I WOULD SAY, WE HAVE REALLY FOCUSED ON THREE SPECIFIC STRATEGIES, WHAT YOU SEE DOWN THE LEFT SIDE HERE, ACROSS THE TOP YOU SEE THE YEAR WE WERE FORM INDEED 2002 AND OUR BUDGET AS IT HAS INCREASED OVER THE YEARS, THANKFULLY THAT'S EYE TYPO FOR THIS YEAR, WE'RE PASSING THROUGH THE 2 MILLION-DOLLAR MARK, WE'RE NOT BACK DOWN TO 2000. SO MY FAULT, NOBODY ELSE'S FAULT THERE. I THINK THE POINT AND MAYBE I SHOULD HAVE BEEN ON THE LAST PANEL. IS THAT WE LEARN YOU'VE GOT TO UNDERSTAND YOUR SCIENCE THERE, 'S THIS HUGE PRESSURE TO JUMP INTO THE CLINIC AND CREATE THE ANIMAL MODELS AND FIGURE OUT WHAT'S GOING ON TO DEVELOP THOSE COMPOUNDS AND GET THEM TESTED BUT UNLESS YOU UNDERSTAND THE BASIC MECHANISMS, YOU'RE NOT GOING TO BE ABLE TO DO THAT SUCCESSFULLY. AND I WOULD SUMMARIZE UNDERSTANDING THE SCIENCE AS THAT'LL TELL YOU WHEN THE SCIENCE IS PRIMED TO ENTER THE TRANSLATIONAL SPACE, IT TELLS YOU WHO ARE THE RELEVANT PLAYERS FOR YOUR DISEASE, AS TO WHO YOU DO NEED TOO NETWORK WITH TO HAVE SUCCESS IN THE LONG RUN. WHAT YOU SHOULD INVEST IN, SO THAT YOU CAN INVOTE THOSE LIMITED DOLLARS REALLY STRATEGICALLY AND IT TELLS YOU HOW TO INVEST THAT AND YOU SEE AT THE BOTTOM, IF THERE'S NOTHING ELSE I CAN TELL YOU, I THINK PARTNE AND LEVERAGE ARE TWO KEY THINGS THAT WE HAVE ENGAGED IN EVERY SINGLE THING WE'VE DONE EVERY STEP OF THE WAY THAT I THINK HAS SERVED US WELL, SO UNDERSTANDING THE SCIENCE WAS THE FIRST THING WE COULD DO WHEN WE DIDN'T HAVE MONEY TO INVEST, WE HAD ENERGY AND TIME AND GOODWILL AND PASSION. AND AT FIRST THAT REALLY SETS YOU UP WELL TO DO, I THINK WHAT WE AS NONPROFIT ORGANIZATIONS DO THE BEST WHICH IS NETWORK. CERTAINLY IN THE BEGINNING WHO DO WE HAVE TO NETWORK WITH, THEY WERE THE WONDERFUL CLINICIANS AND RESEARCHERS HELPING IN THE FIELD WHO HELP TO FOUND THE ORGANIZATION SO THE FOUNDING MEMBERS OF OUR MEDICAL ADVISORY COUNSELS AND I WILL LOOK OUTWARD LIKE ANY SOCIAL ENDEAVOR AND UNDERSTANDING THE SCIENCE TOLD US HERE THAT THE NIH AND NINDS WAS A CRITICAL GROUP FOR US TO INTERACT WITH. IT ALSO TOLD US THAT NOT ONLY DID WE NEED TO WORK FOR INSTANCE, WITH MARK SOUGHTER LAND WHO'SAUR MAIN PROGRAM OFFICER BUT I NEED TO GET TO KNOW EMILY PRETTY WELL BECAUSE THE SCIENCE TOLD US THAT HALF OF OUR PATIENTS HAD THE SAME EXACT PATHOLOGY AS ALL OF ALS. SO RIGHT THERE, THERE'S SOMEBODY CRITICAL WHO NEEDS TO KNOW WHO I AM AND HOPEFULLY WE CAN DEVELOP A GOOD WORKING RELATIONSHIP. IT ALSO NOT US THAT THE NOT ONLY DID WE NEED TO GET NINDS, BUT WE NEED TO GET IT AS LBECAUSE THIS IS A RARE DEMENTIA AND 40% OF OUR PATIENT HIS A SIMILAR PATHOLOGY AS ALZHEIMERS SO A LOT OF OUR EXPERTS A LOT OF THE NEXT CIRCLE OF CLINICIANS AND RESEARCHERS THAT WE NEEDED TO WORK WITH ARE ALL THE PEOPLE AT THE ALZHEIMER'S DISEASE RESEARCH CENTERS. WHICH IS A MAIN INITIATIVE THAT NIA RUNS. IT'S HARD TO SWITCH ORGANIZATION WEES WORK WITH, CERTAINLY WE WORK WIDE--I DON'T KNOW IF LUCY'S STILL HERE TODAY, THE ALS ASSOCIATION, WITH THE ALZHEIMERS DISCOVERY DRUG FOUNDATION, IT TOLD US WHO'S IN OUR WORLD IN THE NONPROFIT SECTOR WHO MIGHT BE WILLING TO CO INVEST WITH US IN THIS--IN DIFFERENT PROJECTS, AND THEN, MOST RECENTLY, IT HELPEDUS DIRECT THIS TO WHICH PARTS AND INDUSTRY MIGHT BE INTERESTED IN OUR SCIENCE IN WORKING WITH OUR PATIENTS AND SEE IT AS AN OPPORTUNITY FROM THEIR PERSPECTIVE AND THEN FINALLY ACROSS THE BOTTOM, UNDERSTANDING THE SCIENCE, KNOWING THE RIGHT PLAYERS, HOPEFULLY, ARE AT LEAST GETTING TO KNOW THEM, REALLY HELPED US I THINK TO MAKE THESE INVESTMENTS STRATEGICALLY AND WHAT I PUT IN BLACK ARE THE THINGS THAT I WOULD CONSIDER THE THINGS THAT--THE PROJECS THAT HAVE MOVED US INTO THE TRANSLATIONAL SPACE. SO YOU SEE, WE WERE A GOOD, I DON'T KNOW EIGHT YEARS OLD BEFORE I THINK WE WERE READY. CERTAINLY HAD THE FINANCIAL CAPACITY, HAD THE RIGHT CONNECTIONS BUT ALSO THE SCIENCE HAS BEEN MOVING TREMENDOUSLY FAST IN THAT PERIOD OF TIME AS WELL, SO I THINK IN A LOT OF WAY ITS WASN'T UNTIL SOMEWHERE IN THE MIDDLE HERE THAT THE SCIENC WAS READY FOR TRANSLATIONAL INVESTMENTS. JUST A COUPLE EXAMPLES, DRUG DISCOVERY IN 2007 WE MET THE ALZHEIMER'S DRUG DISCOVERY FANNATION AND THEY'VE BEEN TREMENDOUS PARTNERS, THEY MATCH OUR DOLLARS, TWO-ONE AND WE'RE ENTERING THE 10th YEAR OF DRUG DISCOVERY AWARD PROGRAM THAT WE NEVER COULD HAVE PRESUMED TO DO ON OUR OWN AT ALL. WORKING WITH NINDS, AND NIA, WE'VE BEEN ABLE TO INVEST AND PARTICIPATE AND DEVELOPMENT OF A LOT OF COMMON RESOURCES, SO THE IPS CELL CONSORTIUM THAT YOU HEARD MENTIONED EARLIER. TOGETHER WE CREATED, WE HOSTED MEETINGS AND WE ACTUALLY AS ALWAYS PAID FOR THE FOOD, BUT WE WERE ABLE TO BUILD A NATIONAL DATABASE WHERE THE DATA THAT'S COLLECT OFFICE OF DIVERSITY OUR PATIENTS ACROSS THE COUNTRY WE W SURE IT COULD BE COLLECTED WITH CDs AND IN A COMMON MANNER AND HELD IN THE SAME PLACE. WE DEVELOPED AN NINDS WITH FDA AND TREATMENT GROUP AND FIVE OTHER NONPROFITS AND YOU CAN SEE THIS YEAR, IT'S ALL--MOSTLY THANK TO THE SCIENCE BUT IT'S ALL COME TOGETHER AND WE'RE INVESTING IN A WHOLE LOT MORE CLINICAL PROGECS. WE DID GET NRDCRN LAST YEAR AND WE DID GET CLINICAL FELLOWSSHIPS FOR THE FIRST TIME, AND WE'RE ALSO DEVELOPING OUR PATIENT REGISTRY FOR THE FIRST TIME. SO AGAIN FROM A PERSPECTIVE OF A YOUNG NONPROFIT. EVEN IF YOU DON'T HAVE THE MONEY AND YOU DON'T KNOW WHAT TRANSLATIONAL SCIENCE IS, THERE'S A WHOLE LOT OF THESE FUNDAMENTAL THINGS CAN YOU DO THAT ARE GOING TO SET YOU UP FOR SUCCESS WHEN THE SCIENCE IS READY AND HAD WHEN YOU DO HAVE A BUDGE TOTE HELP YOU UNDER THAT SPACE. [ APPLAUSE ] >> SO I'M GOING TO TELL YOU A STORY. SO NEXT YEAR WILL CELEBRATE THE 50th ANNIVERSARY OF RHETTY'S SYNDROME ACTUALLY BECOMING A KNOWN CLINICAL ENTITY, SO IT'S ONLY FIT YEAR'S AGO THAT ANDREAS RHETT MADE THE OBSERVATION, SO IF YOU THINK ABOUT PARTNERSHIPS, INITIAL RESEARCH THAT WAS DONE WAS LARGELY FUNDED BY SMALL FAMILY GROUPS. IN 1999, ONLY A LITTLE BIT MORE THAN 15 YEARS AGO, THE GENE MYK P-TWO WAS ASSOCIATE WIDE RHETT'S SYNDROME AND AT THAT POINT IT'S IMPORTANT TO KNOW THAT FUNDING WAS FUNDING FOR A POST DOCTORAL FELLOW IN THE LABORATORY OF KD--SALLY WHA. SO AGAIN A PARTNERSHIP BETWEEN ACADEMIA AND A PRIVATE FOUNDATION TO PUT THESE OBSERVATIONS FORWARD. FROM 1999 TO TODAY, THE LARGEST FUNDER OF RETT HAS BEEN THE PEOPLE AT THAT TABLE, NINDS, AND NHD, NATIONAL INTUITY OF CHILD HEALTH AND HUMAN DEVELOPMENT, TAXPAYER'S MONEY ACROSS THAT PERIOD OF TIME TO ESSENTIALLY UNDERSTAND WHAT THE BASIC SCIENCE OF RETT SYNDROME. IN 2007, ESSENTIALLY THE FIRST GENETIC REVERSALS IN THE FIRST BIOCHEMICAL REVERSALS CAME ABOUT. AND THAT ESSENTIALLY BROUGHT ON A PLETHORA OF MORE KIND OF SCIENCE THAT BROUGHT FORWARD MORE IDEAS OF WOW, WE CAN MOVE FROM THE BASIC SIDE BECAUSE WE'RE STARTING TO UNDERSTAND THE BIOLOGY AND MOVE INTO THE TRANSLATIONAL SITE BUT THAT WILL TAKE PARTNERSHIPS. NOW RIGHT AFTER THAT 1999 OBSERVATION, THE THING THAT'S ISTING IS THAT THE NIH DID A PARTNERSHIP WITH THE CLINICS AROUND THIS COUNTRY TO ACTUALLY FUND A COOPERATIVE AGREEMENT FOR A NATURAL HISTORY STUDY. NOW THAT FIRST NATURAL HISTORY STUDY WAS A NATURAL HISTORY STUDY WITH RETT'S SYNDROME, PRETERM BIRTHER WILSCHEçNGEL MAN'S SYNDROME AND THAT WENT ON FOR 12 YEARS. AND A YEAR AND HALF AGO THAT CONSORTIUM MOVE FRIDAY A THREE SEPARATE DISEASE CONE SORTIUM TO A NEW CONSORTIUM OF RETT'S SYNDROME AND MYT P-TWO DUPLICATION AND THAT WAS A PARTNERSHIP WITH THE FEDERAL GOVERNMENT. AND WHAT'S REALLY NICE ABOUT THIS STORY IS THAT THE INTERNIONAL RETT'S INCHROME FOUNDATION WAS PART OF THAT PARTNERSHIP IN THE FIRST NATURAL HISTORY STUDY, WHICH ONLY FUNDED FOUR SIGHTS AND THE INVESTIGATORS RECOGNIZED THERE WAS NO WAY THEY WERE GOING TO GET THE COHORT OF PATIENTS THAT THEY NEEDED IN ORDER TO ESSENTIALLY STUDY RETT'S SYNDROME THE WAY IT NEEDED TO BE STUDY, INTERNATIONAL RETT'S SYNDROME, PAID FOR TRAVEL CLINICS AND ADDED SEVERAL SITES TO INCREASE THE COHORT, PARTNERSHIP WITH THE FEDERAL GOVERNMENT. IN THE MOST RECENT NATURAL HISTORY STUDY, THE U54, THAT CHILD HEALTH AND NINDS IS FUNDING, THAT WAS INITIALLY FUNDED 11 SITES AND WHAT INTERNATIONAL RETT'S SYNDROME HAS DONE THROUGH APPROVAL PROCESS WITH NATIONAL INSTITUTES HEALTH AND WE ADDED THREE MORE ADDITIONAL SITES. SO NOW WE'RE UP TO 14 SITES THROUGHOUT THE COUNTRY TO DO WHAT? MAKE TRAVEL FOR THE FAMILIES EASIER, TO GET MORE KIDS TO THE CLINICS MORE ADULT WOMEN TO THE CLINICS TO GET MORE OF THE VERY YOUNG BYS WHO SURVIVE TO THE CLINICS SO WE CAN ACTUALLY DID A VERY GOOD NATURAL HISTORY STUDY AND BUILD THE CONTACT HISTORY AND PATIENT REGISTRY. SO THAT YOU THAT'S PARTNERSHIPS. NOW THAT OBSERVATION IN 2007 WITH A GENETIC REVERSAL AND A BIOCHEMICAL REVERSAL LED TO A KAW KACCT COUGHONY MOVEMENT, AND THE NHIRKS CAME IN AND SAID, GUYS SLOW DOWN. YOU'VE GOT TOO MANY MOUSE MODELS, TESTING TOO MANY THINGS. THERE'S NO CONSISTENCY ACROSS ALL OF THESE REVERSALS YOU'RE SEEING AND THE NIH HELD A WORKSHOP WHICH ESSENTIALLY GAVE US IDEAS ON HOW TO MAKE--BUILD CONSISTENCY AND BUILD A PROGRAM THAT THE FDA AS WELL AS PHARMACEUTICAL COMPANIES WOULD ACTUALLY GET INVOLVED WITH. SO LAURA ORGANIZED A WORKSHOP WITH INTERNATIONAL RETT SYNDROME AND RESEARCH TRUST AND THEY SET A NEW BAR. SO WE WENT OUT AND BUILT A PROGRAM, INTERNATIONAL RETT'S PROGRAM CALLED THE SCOUT PROGRAM. WE HIRED A CONTRAST RESEARCH ORGANIZATION, ONE RETT MODEL, SET NUMBER OF PHENOTYPIC AS WELL AS BIODEHAIRIAL PROTOCOLS THAT WILL BE DONE WITH THOSE MICE AND NOW THE PHARMACEUTICAL COMPANIES ARE COMING OUT OF THE WOOD WORK TO GET THEIR MOLECULES OF INTEREST INTO THE PROGRAM. SO THAT CAME FROM A PARTNERSHIP, NIH SETTING A WORKSHOP AND SETTING A SET OF GOALS WHICH WE WENT AHEAD AND FULFILLED. THE NEXT--SO THE PARTNERSHIPS WITH THE BIOTECH COMPANIES IS ONE THAT'S REALLY IMPORTANT. IF YOU BUILD SOMETHING THAT WILL PASS THEIR PRECLINICAL VIEW, RANDOMIZATION, BLINDED, THEY WILL COME AND PLAY. AND AGAIN I'M RIGHT NOW, I'VE GOT MORE BIOTECH COMPANIES THAN I CAN ACTUALLY FUND BECAUSE I ACTUALLY--IT'S NO RISK TO THEM, WE'VE DERISKED IT, YOU BRING YOUR COMPOWBD IN, WE WILL RUN IT THROUGH ITS HURDLES. AND SO THEY LOVE THIS PROGRAM BECAUSE THEY DON'T HAVE TO GO OUT AND TRY TO BREED THESE ANIMALS THAT ARE VERY TOUGH TO BREED. GET THE NUMBERS THAT THEY NEED, THEY JUST COME IN, PLUG THEIR COMPOUND IN AND IT RUNS DOWN THE OBSTACLE COURSE AND WE TELL THEM AT THE END, IT LOOKS INTERESTING OR IT DOESN'T LOOK ANYTHING AND THEY SAY THANK YOU VERY MUCH AND THE THING THAT'S IMPORTANT HERE IS WE KEEP ALL OF THAT INFORMATION, IT'S PROPRIETARY, IT'S THEIR INFORMATION. WE DON'T PUBLISH IT. THEY CAN PUBLISH IT, BUT WE DON'T PUBLISH IT. I KNOW ABOUT IT, AND IF IT LOOKS REALLY GOOD, I BECOME THE JUNKYARD DOG OF TRYING TO GET THEM TO MOVE IT TO LET'S GO TO THE FDA, LET'S HAVE THE PREIND MEETING. LET'S HAVE THE I ND MEETING. SO THAT'S THE TRANSLATIONAL PARTNERSHIP CAME OUT OF THE NIH, WE IMPLEMENTED SOMETHING AND NOW WE'RE DOING IT WITH THE DRUG COMPANIES. SO THIS IS ALL LED TO SOME CLINICAL TRIALS. THERE'S NOW SEVEN CLINICAL TRIALS WITH RETT, AND THE THING AT A WANT TO IMPRESS UPON YOU, AND EVEN THOUGH WALTER IS SAY VERY GOOD FRIEND, I'VE WORK WIDE WALTER WHEN I WAS ACROSS THE STREET AT THE UNIFORM SERVICES, I DON'T WANT YOU TO THINK JUST ABOUT THE NIH. YOU ARE ALL HERE WITH NEUROLOGIC DISEASES, THE D.O.D. HAS A HUGE PROGRAM IN NEUROLOGIC DISEASES. THE BEST DRUG, I HAVE RIGHT NOW IN CLINICAL TRIALS, CAME OUT OF THE D.O.D. WALTER KNOWS THE DRUG, WHEN I CAME TO THE INTERNATIONAL RETT FOUNDATION, HAVING BEEN THE VICE PRESIDENT OF THE D.O.D.'S MEDICAL SCHOOL AND I WAS STUDYING RETT PATHOLOGY, I SAID THAT DRUG WILL WORK OVER HERE, I WENT TO THE DRUG COMPANY AND I SAID ARE YOU INTERESTED DOING A CLINICAL TRIAL ON A RARE DISEASE BECAUSE THEY WERE DOING CLINICAL TRIALS IN TRAUMATIC BRAIN INJURY WITH THEIR DRUG AND THEY SAID SURE, LET'S DO IT. SO THAT PARTICULAR DRUG HAS HAD A SUCCESSFUL PHASE TWO B IN ADULT RETT WOMEN, WE'RE MOVING AND WORKING WITH THE FDA FOR A PHASE TWO B IN PEDIATRIC POPULATION. SO, DON'T BE AFRAID TO LOOK AT WHAT THE D.O.D. IS DOING AS WELL AS NIH. AS WELL AS FDA AND AS WELL AS CDC, AS WELL AS DEPARTMENT OF EDUCATION WHO AS A GREAT DEVELOPMENTAL DISABILITIES PROGRAM. UNDERSTAND WHAT THEY'RE DOING, THE THIS IS THE PARTNERSHIPS THAT WE ALL HAVE TO ESSENTIALLY ENGAGE IN. AND LASTLY ALL OF THIS SPACE, THE BIG THING IS COMMUNICATE, COMMUNICATE, COMMUNICATE. I FORTUNATELY LIVE HERE, SO I CAN GO TO LUNCH WITH LAURA ALTHOUGH LAURA NEVER LETS ME PAY. [LAUGHTER] , I CAN GO TO LUNCH WITH WALTER AND WALTER WILL CERTAINLY NOT LET ME PAY, BUT IF YOU'RE IN WASHINGTON, HAVING BEEN A PROGRAM OFFICER AT NICHD, WE LOVE TO HEAR FROM CONSIT WENTS, CALL THE PROGRAM OFFICERS, THEY WON'T LET YOU PAY, EAT LUNCH WITH THEM, HAVE CONVERSATIONS WITH THEM, AND PICK THEIR BRAINS BECAUSE THAT'S WHAT THEY REALLY LIKE IS WHEN SOMEBODY IS ACTUALLY REALLY CHALLENGING THEM ACADEMICALLY. WITH THAT I'LL STOP AND HAND IT OVER TO ROBERT. [ APPLAUSE ] >> GOTTA BE I CHEAP RESTAURANT. >> SO GOOD MORNING I'M ROBERT MACAFICI, FROM THE CHDI, I WOULD LIKE TO THANK EVERYONE FOR GIVING ME THE OPPORTUNITY TO TALK ABOUT ROBUSTNESS AND CLINICAL MODELS IN FIVE MINUTES. I'LL DO THE BEST I CAN. LIKE MOST OF YOU CHDI IS A NOT FOR PROFIT DRUG DISCOVERY ORGANIZATION, WE'RE TIME MOTIVATED, WE DON'T HAVE COMPETITORS, ONLY COLLABORATORS WHOEVER FINDS THE TREATMENTS WE ALL WIN. WE'RE FOUNDATION FUNDED FROM PRIVATE DONORS WHICH MEANS WE CAN REALLY FOCUS ON REAL THINGS LIKE TRIAL TERM NATIONS RATHER THAN HYPE AND PRESS RELEASES AND LIKE MOST OF YOU WE'RE DEDICATED TO A SINGLE DISEASE THAT'S BEING HUNTINGTON'S, RARE, NEURIE LOGICAL DISORDER, THAT IS STILL A HORRIBLE UNMET MEDICAL NEED BUT WHAT THAT DOES IS IT GIVES US THE CONTINUITY OF FOCUS OVER TIME SO THAT WE DON'T HAVE TO DO SOME OF THE BOBBING AND WEAVING THAT HAPPENS AT LARGER PHARMACEUTICAL COMPANIES IN TERMS OF NEW INDICATIONS AND WHAT IT DOES MEAN IS THAT WE DON'T GET TO HAVE THE VIAGRA MOMENT FOR GOING TO THE CLINIC FOR ONE INDICATION AND FIND OUT THE KLUG IS GOOD FOR SOMETHING ELSE AND AS LONG AS IT'S PROFITABLE IT'S OKAY. WE HAVE TONG ABOUT AND ARCHITECT OUR PORTFOLIO SO THAT TRUSTEES THE GET-GO WE TETHER INTO HD ITSELF AND WE'RE UTILIZING THE VIRTUAL MODEL AND IT'S FAKE AND REAL AND WE'RE NOW 70 PEOPLE WHO WORK WITHIN THE FOUR WALLS OF THE FOUNDATION ACROSS OUR THREE SITES IN NEW YORK, NEW YEARS SCHELA, AND WE COVER SOUP TO NUTS FROM BLUE SKY DISCOVERY WORK ALL THE WAY THROUGH CLINICAL TRIALS AND TRANSLATION AND BETWEEN AND ORCHESTERATE A FAIRLY LARGE EFFORT OF ABOUT 600 FOLKS WORLD WIDE ON EVERY ASPECT OF HD DRUG DISCOVERY. SO I WAS ASKED TO ADDRESS ROBUSTNESS AND REPRODUCIBILITY AND I CAN TELL YOU, YOU'VE HEARD IT TIME AND AGAIN I WAS ON COUNCIL HERE AT NINDS, WHEN SILLER BERG GAVE ONE OF THE EARLY PRESENTATIONS ON THIS TOP AND I CAN I COULDN'T BE MORE SUPPORTIVE OF THIS. I GUESS THERE'S A COUPLE OF QUALIFIERS I WANTED TO PUT IN, WHEN WE TALK ABOUT IT BECAUSE GENERICALLY IT'S LIKE MOTHERHOOD AND APPLE PIE. DO YOU WANT IT TO BE ROBUST AND PROPREDUCIBLE, WHO WILL SAY NO. BUT THEN WHEN YOU GET DOWN TO BRASS TACKS, IT'S A LOT OF IMPLICATIONS, SO I LOT OF US FOR THOSE WHO ARE FAMILIAR, WITH THE TERMS OF QUALITY ASSURANCE, VERSES QUALITY CONTROL, A LOST US THINK ABOUT QUALITY CONTROL AFTERWARDS, INOTHER WORDS THE RESULT IS THERE, IS IT A GOOD RESULT. ONE OF THE THINGS I WANT TO IMPRESS ON FOLK SYSTEM THE UPFRONT THINKING IN DESIGN AND GO IN THE DESIGN AND THE EXPERIMENTS IN THE FIRST PLACE. SADLY ALL TOO OFTEN CAN YOU PREDICT BEFORE THE PIPETTE EVER HITS THE BUFFER THAT THAT EXPERIMENT IS DOOMED FOR FAILURE BECAUSE IT'S NOT POWERED OR NOT DESIGNED PROPERLY FOR THE RELEVANT CONTROLS OR THE ANIMALS WERE NOT GENDER CONTROLLED OR IT WASN'T PROPERLY BLINDED. SO I THINK IT'S REALLY IMPORTANT TO THINK ABOUT THE EXPERIMENTAL DESIGN RIGHT UP FRONT AS PART OF YOUR RESEARCH PRACTICES. AND ANOTHER THING WE HEAR AN AWFUL LOT ABOUT IS HOW BORING AND MUNDANE IT WOULD BE TO HAVE LABS AND REPLICATION OF EXISTS RESULTS AND I GUESS A TWIST ON THIS MIGHT BE A BIT CONTROVERSIAL IS THAT IN MY MIND, I THINK IT'S RATHER THAN JUST TRY TO REDO THE EXPERIMENT, I'S MORE IMPORTANT TO CONFIRM THE BIOLOGICAL FINDING, THE ESSENCE OF WHAT WAS REPORTED. BECAUSE IN THAT CASE, YOU MIGHT HAVE A SLIGHTLY DIFFERENT SET OF EXPERIMENTAL RESULTS, BUT IF AN ORTHOGONAL SET OF LIABILITIES IN THE DESIGN OF THAT EXPERIMENT, BUT THEY RECONVERGEOT FACT THAT MODULATING THIS TARGET WITH THAT PHARMACOLOGY IN THIS REGION OF THE BRAIN HAS SOME POSITIVE OUTCOME, THEN YOU START TO HAVE THE TYPES OF SCIENTIFIC CONVERGENCE, THAT MEANS YOU'RE PROBABLY ON TO SOMETHING THAT'S REAL. THE OTHER THING THAT RELATES TO ROBUSTNESS AND REPRODUCIBILITY IS HOW MUCH TIME AND EFFORT YOU SHOULD PUT INTO IT. AND I GUESS, WHAT I WOULD SAY IS IT SHOULD BE PROPORTIONAL TO THE AMOUNT OF BETS YOU'RE GOING TO PLACE. HOW BIG OF A FOUNDATION IS THIS, SADLY WE SEE CLINICAL TRIALS THAT ARE BASED ON JUST A FEW PUBLICATIONS, MY GOODNESS, IF YOU'RE GOING IT TIE UP THE LION'S SHARE OF A RARE DISEASE POPULATION, FOR MANY YEARS, DON'T YOU WANT TO MAKE SURE THAT YOU'RE ON REALLY SOLID FOOTING, SO THAT'S WHY WHERE I WOULD INVEST TIME AND EFFORT, IF IT'S SOMETHING THAT'S AT THE BEGINNING OF THE PIPELINE, YOU MIGHT BE WILLING TO TAKE ON A BIT OF RISK AND REALIZE THAT THESE THINGS MAY FALL OUT OF BED DOWN STREAM, BUT I WOULDN'T NECESSARILY PUT THE SAME DEGREE OF RESOURCES INTO CONFIRMING THOSE OBSERVATIONS UP FRONT. SORT OF A NATURAL VETTING OF THESE THINGS AS THEY WORK THEIR WAY DOWN THE DRUG DISCOVERY PIPELINE. I WOULD ACTUALLY CORRECTED THE THIS NEXT BULLET, NOT SO MUCH TO SAY I THINKLE BUT INDIVIDUAL INVESTIGATORS ARE ILL POSITIONS TO UNDERSTAND HOW RIGOROUS--HOW RIGOROUS A RESULT NEEDS TO BE IN THE CONTEXT OF A DRUG DISCOVERY PROGRAM. SO I FORGET WHO IT WAS EARLIER, TALKED ABOUT THE HICKS BOSUN PROBLEM, OTHER FIELDS LIKE PHYSICS FIGURED IT OUT ALREADY. IT TAKES A VILLAGE, THE IDEA THAT A SINGLE INVESTIGATOR NOW KNOWS EVERYTHING ABOUT PHARMACOKINETICS PHARMACODYNAMICS, ABOUT ELECTROPHYSIOLOGY IS LUDACRIS, AND I'M A BIOLOGY BY TRAINING I LOOK AT A COMPOUND AND YOU KNOW LIKE MAYBE A COUPLE OF THINGS I CAN TELL IF THE COMPOUND'S REALLY BIG OR IF IT'S GOT LIKE SOME, YOU KNOW NASTY FUNCTIONAL GROUP THAT BIT ME IN THE BOTTOM, YOU KNOW HISTORICALLY, BUT I'M NOT A METRICS DININAL CHEMIST, YOU NEED TO GET THE RIGHT PERSON TO EVALUATE HOW RIGOROUS AND ROBUST A RESULT IS, BASED ON EXPERTISE, LASTLY I WOULD SAY, THE BIG THING IS TO ADOPT A KILLER MENTALITY. YOU KNOW, LIKE TWO OFTEN WE'RE IN THIS MODE OF TRYING TO PROP THINGS UP BECAUSE WE WANT THEM TO MOVE FORWARD, LIKE I CALL BS ON THAT, WHAT WE SHOULD BE DOING IS KILL THESE THINGS, TRUST ME IF YOU HAVE A SOLID OBSERVATION WITH REAL BIOLOGY, IT WILL SURVIVE NO MATTER WHAT YOU THROW AT IT. SO LET'S START ADOPTING THE KILLER MENTALITY. WE WERE ALL TRAINED THIS WAY WHEN WE WERE IN SCHOOL, TO TRY AND INVALIDATE THE MENTAL HYPOTHESIS, AND SOMEHOW WE LOST OUR FOOTING AND GOT INTO THE PROMOTION BUSINESS AND THAT'S PART OF THE PERSERIOUS INCENTIVES THAT DON'T HOLD UP. OKAY, SO THERE'S ACTUALLY AN ANIMATION HERE THAT'S NOT CAPTURES BUT BASICALLY THE DOUBLE EDGED SWORD OF HAVING A MONOGENIC DISEASE IS THAT WE HAVE GENE WE KNOW CAUSES HUNTINGTON'S. WE KNOW THAT THIS IS THE PROTURBATION THAT UNDERLIES THE PATHOPHYSIOLOGY, SO THE VERY EASY THING TO DO IS TO TAKE THAT GENE IS PUT IT INTO MODEL ORGANISMS, NOW I HAVE THE ZEB WAFISH, MOUSE, RAT SONG BIRD SHEEP, BIG OR NONHUMAN PRIMATE THAT IS HAPPIER WHEN IT EXPRESSES EXPANDED HUNTINGTON'S, OKAY? BUT I HAVE NO IDEA WHAT MEANS FOR THE HUMAN DISEASE. SO THE MANTRA WE SHOULD ADOPT IS THAT ALL MODELS ARE WRONG AND SOME MODELS ARE USEFUL AND WE SHOULD USE THE MODELS BASED ON WHAT WE ANSWER AND IT'S RIDICULOUS WHAT HAPPENS IN A BIG BRAIN OVER 40 YEARS, IN A ZEBRAFISH IN FIVE MINUTES. IT'S NOT GOING TO HAPPEN. SO I THINK YOU HEARD A LOT ABOUT THIS FROM OTHERS TODAY, IS REALLY BEING STEEPED IN A MECHANISTIC HYPOTHESIS, AND THERE ISN'T A GOOD ANIMAL MODEL OR A BAD ANIMAL MODEL THAT'S FIT THE PURPOSE, ONE THAT ALLOWS YOU TO ANSWER A PARTICULAR QUESTION AND THE PROTURBATION IN THAT CASE, MAY NOT BE HUNTINGTON ITSELF, THAT MEANS I'M GOING OVER [PHONE DINGS ] IT MAY NOT BE HUNTING ITSELF IT MAY RELATE TO THE FARM CODYNAMMIC MARKER FROM THE HUMAN SUBJECT IT WAS PULLED OUT OF. AND THEY'RE ALSO REALLY STRONG AND IMPORTANT PRACTICAL CONSIDERATIONS IN TERMS OF THROUGH PUT AND CYCLE TIME AND QUALITY THAT'S ASSOCIATE WIDE THESE THINGS AND IN SOME CASES HAVE YOU A LOT OF IDEAS. YOU WOULD LIKE TO SCREEN THE ENTIRE GENOME THAT,'S PROBABLY MORE PROPERTILY DONE IN FLIES THAN IN MICE. IN OTHER CASES YOU'RE GOING TO NEED A LARGER SPECIES FOR INTRUSION OF A LARGE MOLECULE THAT MIGHT REQUIRE A SHEEP OR NONHUMAN PRIMATE BRAIN. SO REALLY THINK ABOUT BEING FIT TO PURPOSE. AND I GUESS THE LAST THOUGHT IS TO MAKE SURE THAT YOU'RE USING THE ANIMALS, NOT SO MUCH AS A GATE BUT AS AN ACCELERATOR. SO THERE ARE MENTORSHIP SKILLY OF EXAMPLES OF BOTH ENDS OF THE SPECTRUM OF TUMOR EXTEN KEEN O GRAPHS AND DIABETES, AND THEN SADLY FAIL WHEN THEY GET TO HUMAN TRIALS AND OTHER EXAMPLES WHERE PEOPLE ARE INCESTENT ON GETTING WHAT LOOKS LIKE FACE VALIDITY OF EFKASP A R NEUROECTODERMAL THE THEIR ANIMAL MODELS AND THEY WON'T TAKE TAKEN--THEY COM COMPOUND TO A CLINIC UNTIL THEY CURE A MOUSE. I SAY BOTH OF THOSE ARE WRONG, IF YOU CAN MOVE A RELEVANT NEEDLE TO THE TIED TO THE HUMAN PATHOPHYSIOLOGY BECAUSE AT THE VERY LEAST YOU'LL GET AN ANSWER OUT OF THE CLINICAL TRIAL AS TO WHETHER THERE'S CONNECTIVITY IN THE PATHWAY MECHANISM IN THE ANIMAL MODEL AND THE HUMAN DISEASE, THANKS. [ APPLAUSE ] >> SO BAVANI, SHANKAR, AND I'M WITH ASTRAZENECA, AND WHAT STRUCK ME ABOUT LISTENING TO THE CONVERSATIONS IS WIRE NOT THINK BEING IT PRACTICES THE NONPROFIT OR ACADEMICSER, WE'RE NOT THAT FAR AWAY, WE'RE THINKING IN THIS A SLIGHTY DIFFERENT PERSPECTIVE AND I WANT TO SHOW THE AFT RAZENECA PERSPECTIVE IF YOU WILL, THE LAST DECADE HAS BEEN VERY DIFFICULT BECAUSE WE JUST DON'T UNDERSTAND THE SCCE BEHIND IT. AND JUST GOING AFTER THE LARGEST POPULATION THAT YOU CAN TRYING TO CREATE A BLOCKBUSTER DRUG DOESN'T WORK ANYMORE. SO ONE OF THE THINGS--I WILL JUST FLIP THROUGH THE ANIMATION IN THE INTEREST OF TIME. ONE THING WE'VE CHOSEN TO DO IS CHANGE THE FUND AMILLIOAL WAY OF THINKING OF HOW WE APPROACH DRUG DEVELOPMENT AND RESEARCH AND HOW WE OPERATE, ONE BIG PIECE WE'VE GONE IS TAKEN AWAY THE NOT INVENTED HERE SYNDROME, WE USED TO BE FAT AND HEAVY, 600 PEOPLE, AND THE LAST USEFUL DRUG CAME OUT YEARS AGO AND SOMETHING WAS NOT WORKING RIGHT AND THE OTHER PIECE IS HOW CAN WE CORRECT THAT AND LET GO OF THAT. SO THE THEME THAT'S BEEN TALKED ABOUT, ALL MORNING, IS COLLABORATION. STOP FOCUSING INWARD, LOOK INSIDE, LEVERAGE THE BEST SCIENTISTS, ACADEMIC OUT THERE AND BUILD A NETWORK THAT WILL LEAD TO A SUCCESSFUL DRUG THAT WILL MEET UNMET NEEDS. AND WAS PART ONE OF WHAT WE DID AND WE BROUGHT IN THE RIGHT PEOPLE. WE TALLLY BROUGHT IN FRESH BLOOD, IT SOUNDS VERY MA CAB BUT WE BROUGHT--YOU KNOW WE DID GET RID OF THE PEOPLE OF WHOITUTE EVERYBODY THAT IS TO BE DONE IN ASTRAZENECA AND BRING IN FROM SMALLER ORGANIZATIONS, AND SUCH AS MYSELF, I NEVER WORK INDEED PHARMA BEFORE THIS, LET'S THINK ABOUT THIS DIFFERENTLY? HOW CAN WE COLLABORATE AND WORK TOGETHER? SO THAT WAS THE FIRST PIECE OF IT. SECOND, OF COURSE, I MEAN WE ARE A BUSINESS, WE HAVE TO BUILD A PORTFOLIO, WE CAN'T JUST WORK ON THE BASIC SCIENCE, THE BASIC WERE AND NOT EVENTUALLY BRING A DRUG TO MARKET. SO WE'RE BUILDING AGAIN, AS CAN YOU SEE THE THEME OF COLLABORATION, WE'RE BUILDING A PORTFOLIO BY WORKING WITH DIFFERENT SOURCES. TWO THINGS I NOTICED I LEFT HERE ARE NONPROFITS AND THE GOVERNMENTAL INSTITUTIONS, BOTH OF WHOM WORKING WITH EXTENSIVELY CURRENTLY, BUT PART OF WHAT WE'VE BEEN REMIED TO DO, THE LAST TWO OR THREE YEARS HAS BEEN TO BUILD A PORTFOLIO THAT MAKES SENSE THAT INCREASES TO YOUR SUCCESS AND THAT WAY WE UNDERSTAND THE SCIENCE. UNDERSTANDING THE SCIENCE SOUNDS EASY BUT IT'S NOT OF COURSE, ONE OF THE THING WHAT'SY NEED TO DO IS WHAT HAVE WE BEEN DOING WRONG SO WE CAN FIX IT. THIS IS A PAPER THAT CAME OUT IN HR REVIEW A COUPLE YEARS AGO, I THINK THE LEAD AUTHOR, AND THE MEDICINE AND NEUROSCIENTISTS. AND AS YOU CAN SEE, ASTRAZENECCA AND DISPLAYED THERE. BUT WHAT'S TO DOUBT AND HAPPY TO SEND THIS OVER TO ANYBODY WHO'S INTERESTED, IS MORE THAN HALF OF THE STUDIES--OOPS I DON'T KNOW WHAT I DID. SORRY. MORE THAN HALF OF THE STUDIES FAILED BETWEEN PHASE ONE AND PHASE TWO, PROOF OF EFFICACY, PROOF OF MECHANISM, AND THEY FAIL BECAUSE THERE WAS NO LINKAGE TO THE DISEASE ESTABLISHED. RIGHT, BAD ANIMAL MODELS AS THE DOCTOR WAS MENTIONED, NOT UNDERSTANDING THE SCIENCE, SOME ARE MONOGENIC DISORDERS, SOME ARE NOT MORE COMPLICATE BUD UNDERSTANDING THE SCIENCE AND IF WE DOT SAME THING OVER AND OVER AGAIN, AND EXPECT DIFFERENT RESULTS, YOU KNOW WHAT WE ARE. SO THE RECOLLECT PIECE OF WHAT WE HAD TO DO WAS CHANGE AGAIN, HOW DO WE DEVELOP DRUGS. HOW DO WE CONDUCT RESEARCH, SO WE CAN CHANGE THESE STATISTICS AROUND AND THAT COMES TO THE LAB. EVERY COMPANY, EVERY INSTITUTION HAS THE MISSION STATEMENT FOR US, IT'S THE FIVE Rs FRAMEWORK, FAIRLY OBVIOUS, RIGHT TARGET, UNDERSTANDING THE GENETICS BETWEEN THE TARGET AND THE DISEASE AND UNDERSTANDING HOW AND WHY THIS DRUG OR THIS TARGET WOULD WORK. SECOND ONE, WHICH IS EASILY FIXABLE OF COURSE, IS FINDING THE RIGHT TISSUE. WHERE DOES IT NEED TO BE DISTRIBUTED, WHERE DOES IT NEED TO BE RETAINED, UNDERSTANDING PKPD CORRELATION RELATIONSHIP, SAFETY, OBVIOUSLY DON'T HAVE TO SAY MUCH ABOUT IT. AND WHAT WAS FUNDAMENTAL DIFFERENT FOR US IN ASTRAZENNICCA, IN THE RIGHT PATIENTS AND RIGHT COMMERCIAL. IT WAS AN UPHILL BATTLE TRYING TO CONVINCE COMMERCIAL THAT IF WE WENT TO A TARGETED AND FOCUSED POPULATION THAT WE WOULD STILL NOT BE ABLE TO GET A SUCK SUSESFUL DRUG TO THE MARKET. SO THAT WAS A CHALLENGE I THINK WITH GETTING OVER AND GETTING ACROSS TO THEM. BUT UNDERSTANDING THE PATIENT POPULATION AND THAT'S WHERE I THINK A LOT OF TODAY'S TOPIC WILL RUNNING A BELL AS TRANSLATIONAL, UNDERSTANDING WHAT THE SYMPTOMOLOGY, THE EETIOLOGY AND MUSEUM MAN DISEASES AND OOH PLYING IT VERY EARLY ON INTO OUR PROGRAM SO THAT WE ARE INCREASING OUR CHANCE OF SUCCESS IF THAT MEANS ONLY A SMALL SUBSEGMENT OF THE POPULATION, WILL BE ABLE TO TAKE THE DRUG OR THE LABEL AND MORE NARROW THAN WE WOULD LIKE IT TO BE. THAT WAS ONE OF THE IMPORTANT THINGS THAT WE STARTED DOING THAT IS VERY DIFFERENT FROM MAYBE AFT RAZENNICCA, 10 YEARS AGO, OR MAYBE MOST OF BIG PHARMA AND YOU CAN SEE THAT THE FEW COMPANIES THAT ARE STILL THERE AND THE BIGGER PHARMA ARE ALL EMPLOYING THIS KIND OF APPROACH, WORKING MORE COLLABORATIVELY WITH ACADEMICS AND NONPROFITS. AND TRYING TO ANSWER THE QUESTION, HOW DO WE THEA A VERY EARLY STAGE, EARLY RESEARCH BUILD INTO IT WHAT IS NECESSARY TO MAKE THE DRUGS SUCCESSFUL IN THE CLINIC AND NOT HAVE THIS ATTRITION THAT WE SEE. AND I THINK YOU KNOW HOPEFULY IN THE AFTERNOON SESSION WE CAN TALK A BIT MORE ABOUT THAT AS WELL. [ APPLAUSE ] >> GREAT, THANK YOU VERY MUCH. I AM GOING TO TALK ABOUT SOMETHING A LITTLE BIT DIFFERENT HERE AND IT'S A HYBRID MODTHEY'LL WE CREATED ABOUT TWO YEARS AGO FOR TRYING TO ADVANCE VERY EXCITING SCIENCE IN THE PRECLINICAL SPACE THROUGH TO PROOF OF CONCEPT STUDIES IN PATIENTS. WHICH IS WHERE WE ALL WANT THESE TO GO. CYDAN WAS ESTABLISHED TO RAISE CAPITAL FROM FORME SUITICAL COMPANIES TO GO OUT AND IDENTIFY THESE EXCITING OPPORTUNITIES WORLD WIDE. WE HAVE A SET OF CRITERIA WHICH I'LL TELL BUT IN A FEW MOMENTS TO GO AND ARE THESE OPPORTUNITIES WE THINK THAT ARE READY TO MOVE FORWARD INTO STUDYING WHERE WE CAN GO AND ASK WHAT ARE HOW ARE BUST ARE THESE WITH THESE OPPORTUNITIES THAT WOULD INDICATE WHETHER THIS COULD TRULY HELP PATIENTS OR NOT. AT THE END OF THIS PROCESS AND IT'S THE END OF THAT BLUE ARROW YOU SEE THERE, IS TO GO AND CREATE FIVE-EIGHT NEW COMPANIES EACH OF THEM FOCUSED ON DIFFERENT WEAR DISEASE AND EACH OF THEM ADVANCING THERAPEUTICS THROUGH THOSE PROOF OF CONCEPT STUDIES, THROUGH A STANDARD INVESTMENT STRATE. TO DO THIS, WE'RE FOCUSED ON MONOGENIC DISEASES, NOT JUST IN NEUROLOGIC SPACE BUT QUITE BROADLY ACROSS DISEASE AREAS, WE BROUGHT TOGETHER AND EXPERIENCED GROUP OF PEOPLE TO IDENTIFY DRUGS AND ADVANCING THROUGH PRECLINICAL STUDIES AND INTO THE CLINIC AND THEN WE WORK COLLABORATIVELY WITH THE FOLK WHO IS HAVE THESE ASSETS, THE SCIENTISTS, THE NONPROFITS, GOVERNMENT ORGANIZATIONS, SMALL COMPANIES AND LARGE COMPANIES TO GO IN AND IDENTIFY WHAT THE KEY EXPERIMENTS TO BE CONDUCTED TO ADVANCE THE POTENTIAL THERAPY FORWARD. THIS IS THE FIRST TWO YEARS OF OUR EXPERIENCE SO FAR SO WE LOOKED AT 550 OPPORTUNITIES AS CAN YOU SEE HERE, AND IN THE BOTTOM BOX, YOU--IN THE INITIAL SCREEN BOX, CAN YOU SEELET SORT OF THINGS WE'RE LOOKING FOR AT THIS STAGE OF DEVELOPMENT AND THE VAST MAJORITY OF THESE, SOMEWHERE IN THE NEIGHBORHOOD OF 60%, THERE WAS NO AGENT IDENTIFIED OR THE MECHANISM OF ACTION WAS NOT CLEAR TO US OR INVOLVED FAIRY DUST AND A PRIORI WE'RE NOT SET UP TO GO AND ANSWER THOSE QUESTIONS. HOW DOES THAT WORK IN THE A BLACK BOX? AND CAN WE GO FIND SOMETHING THAT GOES AND HIT THIS IS PARTICULAR MECHANISM OF ACTION? WHAT WE HAVE DONE IS WE WORK COLLABORATIVELY WITH PATIENT ORGANIZATIONS AS WELL AS INVEORS TO HELP THEM GET THIS DATA PULLED TOGETHER IN THEIR LABORATORIES OR GROUPS SO WE CAN TAKE TO THE NEXT END STAGE AND WE'VE DONE THAT IN PROBABLY ABOUT 15 DIFFERENT DISEASES TODAY. AND THROUGH PART OF THAT WORK, THEY HELPED THOSE ORGANIZATIONS INNERCREASE THE NUMBER OF THINGS INTO THIS AREA OF DEVELOPMENT FOR US, THE FREQUENCE ATAXIA, ON THE BOARD OF DIRECTORS AND IT'S BEEN A FRUITFUL PROJECT FOR US. THE NEXT STAGE OF DEVELOPMENT IS IN GREEN HORMONE AND THESE ARE THE OPPORTUNITIES WHERE WE WORKED OUT PLANS TO GO AND ADDRESS WHAT ARE THE MISSING PIECE OF DAT AWHAT IS THE DERISKING PLAN TO MOVE THINGS FORWARD, IDENT WHAT IS THE TRUE EPIDEMIOLOGY AT THE INDICATION WHERE THAT'S POORLY UNDERSTOOD AND FIGURE OUT WHAT IS THE CLINICAL PATH TO BE ABLE TO GET THAT CONCEPT IN MATH, AND GO AND HAVE EXCITING SCIENCE AND NO PATH FORWARD CLINICALLY, IS NOT STHING WE CAN WAVE CAPITAL AROUND AND MOVE FORWARD AND DEVELOP THERAPIES TO PATIENTS. OF THOSE 50 SORE SO OPPORTUNITIES WE SET ABOUT TO GO AND ANSWER QUESTIONS IN PHARMACOLOGY, MANUFACTURING TOXICOLOGY AND SO FORTH AND SO FAR WE CREATED ONE NEW COMPANY FROMLL THESE EFFORTS, COMPANY CALLED BUTESQE, THROUGH THE NIH PROGRAM, WE ANTICIPATE CREATING THREE MORE COMPANIES IN THE NEXT NINE MONTHS BASED ON PROJECTS WE'RE WORKING ON TODAY. I DEPARTMENT TO HIGHLIGHT FOR YOU SORT OF WHAT OUR EXPERIENCE HAS BEEN SO FAR WITH PROJECTS WE HAVE BROUGHT IN-HOUSE TO DATE. AND AS CAN YOU SEE, ABOUT HALF OF THEM OR SO HAVE BEEN TERMINATED DURING THESE DE-RISKING STUDIES. THE VAST MAJORITY OF THESE WERE TERMINATE BECAUSE THE PHARMACOLOGY DID NOT TURN OUT TO BE ROBUST. WE'RE NOT ABLE TO EXTEND THESE FINDINGS INTO OTHER ANIMAL MODELS OR INVITRO SYSTEMS OR TED UP THE MECHANISM OF ACTION WAS NOT AS ANTICIPATED AND WAS IN FACT A BLACK BOX. IN A FEW CASES WHERE YOU SEE PHARMACOLOGY AND BUSINESS, WE WENT BACK TO THE ORIGINAL GROUP AND ASKED THEM COULD YOU PROVIDE US MORE INFORMATION ON THIS, OR COULD YOU DO THESE STUDIES TO ALLOW US TO THEN MOVE THIS PROJECT FORWARD AND IN MOST OF THESE CASES WE SAID WE'RE NOT INTERESTED IN DOING THAT OR WE DON'T THINK IT'S IMPORTANT. WE HAVE SEVERAL PROJECTS AS CAN YOU SEE, BOTH IN THE NEUROLOGIC AREA AS WELL AS OTHER AREAS THAT ARE MOVING FORWARD TODAY AND AS I MENTIONED WE CREATED ONE COMPANY IN A LYSOSOMAL STORAGE DISEASE CALLED BUTEXC, THE LAST THING I WANT TO HIGHLIGHT FOR US, ARE THE THINGS THAT WOULD TRULY IMPACTFUL AND CREATE MORE COMPANIES INTO THAT FIRST BOX AS HIGHLIGHTED BY ROBERT AND OTHERS AND THAT IS A ROBUST DATA PACKAGE AND IT'S AMAZING ALMOST EVERYONE CAN AGREE WE WANT ROBUST DATA AND ALMOST EVERYONE HAS DEFINITIONWHAT THAT MEANS. I WAS ENGAGE WIDE A CONVERSATION WITH A EUROPEAN GROUP THAT TOLD ME OUR DATA IS ROBUST AND ONE PERSON IN OUR LABORATORY CAN DO THE EXPERIMENT. BUT EVERY TIME THIS PERSON DOES IT WORKS. AND AS I EXPLAINED IT MAY BE FABULOUS AND PRODUCE UPPER PAPERS ININATE AND YOU ARE SCIENCE, IT'S UNLIKELY TRANSLATE INTO MUSEUM TAN CLINICAL STUDIES WHERE THE PATIENTS ARE NOT INBRED EATING MOUSE CHOW UNDER CONTROLLED CONDITION OPEN SOURCE SOFTWARE I WOULD ENCOURAGE WILL OF YOU IN WORKING WITH, ALL OF US WHO HAVE THE SAME OBJECTIVE OF ADVANCING THERAPIES TO BASICALLY PUSH HARD ON THEM. TO DEMONSTRATE REPRODUCIBLE DATA, THAT MEANS THE SAME EXPERIMENT DONE TWICE AND GETTING A SIMILAR RESULT, NOT TOO DIFFERENT EXPERIMENTS DONE TWICE, GETTING RESULTS CAN YOU RELATE SOMEHOW TOGETHER, USING CONTROLS IN THOSE STUDIES, BOTH NEGFIVE AND POSITIVE CONTROLS AND USE THEM IN ALL THE STUDIES. THE REASON WHY WE HAVE THEM AS CONTROLS IS ESSENTIALLY TO CONTROL FOR THE EXPERIMENT. NOT BECAUSE WE DID IT ONCE AND IT LOOKED PRETTY GOOD BACK THEN. AND THEN HIGHLIGHTED RUN ANIMAL STUDIES AND OTHER STUDIES THAT ARE POWERED STATISCALLY SO THAT THE DATA COMES BACK AND CAN YOU GO AND SAY, THERE IS A ROBUST AS WELL AS SIGNIFICANT RESULTS THAT I HAVE SOME HOPE OF TRANSLATING AS I MOVE IT FORWARD THROUGH DRUG DEVELOPMENT. THANK YOU VERY MUCH [ APPLAUSE ] >> THANK YOU AGAIN. THAT WAS FANTASTIC SO WE COVERED SEVERAL FUN TOPICS HERE, PRIORITY SETTINGS, DAT AROBUSTNESS, REPRODUCIBILITY, ROBERT DID A FANTASTIC JOB OF JUST OUTLINING SOME OF THE CHALLENGES THEY HAVE IN TERMS OF GETTING THINGS FROM EARLY DISCOVERY INTO A CLINICAL SETTING. TECHNICAL EVALUATIONS, DUE DILIGENCE, PARTNERSHIPS, SO THE IDEA OF GETTING PARTNERSHIP IN PLACE, EARLY, LIKE WAS OUTLINED TELL BE CRITICAL FOR US. AS MAY MATTER OF FACT ASTRAZENECA HAS PARTNERED TO WITH UPON OUR PARTNERS TO PUT A KEY CLINAL COMPOUND INTO TRIALS AND WE'RE HAPPY ABOUT IT BUT NOT JUST ON THE DOLLARS, BUT ON THE KNOW-HOW WOULD HAVE ALMOST BEEN IMPOSSIBLE FOR OUR INVESTIGATOR TO DO AND JUST LIKE WE TALKED ABOUT OUR INVESTIGATORS FANTASTIC IN TRYING TO FIGURE OUT THE DISEASE MODEL, UNDERSTAND THE STRUCTURAL ACTIVITY WORK, PHARMACOLOGY BUT BEYOND THAT WITHOUT THE RESOURCES THAT ARE NOW BEING BROADENED BY ASTRAZENECA, WOULD HAVE BEEN A CHALLENGING TASK FOR US AND TAKEN MANY, MANY YEARS TO DO AND WITH THAT HELP WE'RE HOPING TO MAKE THAT HAPPEN WITHIN THE NEXT COUPLE OF YEARS. ADVANCING SORT OF DISEASE LINKED FROM PHASE ONE AND TWO. WE TALKED ABOUT THIS INTERNALLY, THE LANDSCAPE CHANGED. MANY OF US FOCUSED ON TOXICOLOGY AND PROFILES THEREOF 10 YEARS AGO, A LOT OF THESE ATHLETES HAVE BEEN DEVELOPED BUT THE DISEASE MODELS, UNDERSTANDING THE BASIC BIOLOGY HAS BECOME SO CRITICAL THAT WE'RE PAYING ATTENTION TO THAT, THE FIVE ARE OUTLINE CRITICAL AND I CAN MAKE A POINT OF PUTTING THEM ON MY DESK SO KIREFER TO THEM EVERY TIME. SO ONE THING I CAN REFER TO--BEFORE YOU GO TO QUESTIONS FROM YOU, I WANT TO MENTION SOMETHING STEVE BROUGHT UP IN TERMS OF CENTER PROGRAMS. SOPHISTICATED I SEE JOHN KEEN OVER THERE AND HE RUNS A PROGRAM THAT'S BEEN INVOLVED WITH ALMOST ALL THE DRUGS THAT HAVE ACTUALLY GONE INTO CLINICAL TRIALS AND IT'S BEEN APPROVED FOR EPILEPS SCHEBEYOND. SO THESE PROGRAMS WORK AMAZINGLY WELL AND HE'S SPEAR HEADED THE PROGRAM FOR THE LAST FEW YEARS AND DONE SIGNIFICANT CHANGES SO TALK TO THEM WHEN YOU HAVE A TIME AND TRY TO UNDERSTAND HOW THESE CENTERS WORK AND IN FACT EVERY WHERE WE GO, PEOPLE REALLY ARE TALKING ABOUT THIS BEING A SUCCESSFUL PRACTICAL, PEOPLE ARE LOOKING FORWARD TO SENDING COMPOUNDS TO JOHN AND HIS TEAM TO GET A CRITICAL EVALUATION BASED ON STATE-OF-THE-ART MODELS AND MODELS THAT HAVE ACTUALLY BEEN VALIDATED AND WHICH IS ACTUALLY THE CRITICAL PIECE FOR US. SO WITH THAT I'LL STOP, SUSAN DO HAVE YOU COMMENTS? >> I THINK I APPRECIATE THE NUMBER OF PANELS--WHOOPS, SORRY--SNOW, I THINK IT'S REALLY--WE ALL WANT THE MAGIC COP POUND SO BAUDLY AND IF THERE'S SOMETHING--BADLY AND IF COMES UP, IT'S SEDUCTIVE TO WANT TO ROOT FOR IT AND MAKE SURE IT WORKS AND YOUR POINT IS WELL TAKEN THAT THAT'S THE POINT WHERE YOU NEED TO BE THE MOST RIGOROUS AND AS THE TOUGHEST QUESTIONS, AND NOT GO, GO LIGHT ON IT AND THAT'S THE WAY WE'RE GOING TO SERVE OUR PATIENTS AND OUR FAMILIES THE BEST. AS WELL ASEUR INVESTORS AND DONORS. >> OKAY, WE GO TO QUESTION FIST WE HAVE ANY. WE HAVE 10 MINUTES IF WALTER WILL GIVE US MORE TIME WE'LL TAKE THAT BUT WE DON'T WANT TO COME IN THE WAY OF YOU HAVING LUNCH SO IF THERE ARE ANY QUESTIONS WE'LL TAKE THAT. BESIDES THAT WE HAVE RPGHTS TOPICS WE WOULD LIKE TO BRING UP, WE HAVE ABOUT THREE OF THEM IN OUR BACK POCKETS. SO WE'LL SEE WHERE IT GOES. >> SO COMPLETELY AGREE OF ROBUSTNESS AND REPRODUCIBILITY, I'M JUST WONDERING WHETHER ON THE DRUG DEVELOPMENT SIDE, ARE THERE OTHER REASONS WHY, A CERTAIN COMPOUND DEVELOPS ARE KILLED SO TO SPEAK A PART FROM THAT IS THERE CHANGING LANDSCAPE, I'M THINKING OF WHAT'S HAPPENING MAYBE IN THE CANCER FIELD WHERE WE ARE STARTING TO NOVARTIS, DESIGN TRIALS AROUND, ONE TRIAL HAVE HEAD NOTHING THE RIGHT DIRECTION AND THE DISEASE WHERE WE MIGHT TARGET PATHWAYS AND NEW DISEASE INDKEGS AND MAYBE FROM THE PATIENT POPULATION RECOGNIZING AND THAT HAVE TARGETS WITHIN RARE DISEASES AND COUPLE OF THINGS THAT WE WERE TALKING ABOUT AT BREAK AND SEVERAL OF THE NEUROLOGICAL DISEASES, WHILE THEY APPEAR TO BE INDEPENDENT DISORDERS, THERE IS A LOT OF AND AND FOR THE COHESIVE EFFORT TO PUT TOGETHER TO DEVELOP OR WHAT I CALL A MATRIX OF DISEASES, VERSES TARGETS AND I THINK VERY SIMILAR TO ASTRAZENECA, WE DO A LOT OF THOSE TRIALS YOU DESCRIBED. I THINK IT WOULD BE VERY USEFUL IF THE SAME SET UP COULD BE ESTABLISHED WITH THE NEUROLOGY DISEASES BECAUSE OF THE OVERLAP, AND OTHERS TO GET TOGETHER, AND IT'S HIGHLY POSSIBLE, AND WORK IF ONE DEC, THEY ALREADY STARTED SEEING THAT THERE IS A LOT OF OVERLAP BETWEEN THE FAMILIES FORMS AND THEY'VE ALREADY STARTED WORKING ON THAT. AND THE DISEASE COMING IN, AND LOOKING FOR SCIENTIFIC VOLUNTEERS. ONE THING THAT I'M ENCOURAGED AND COLLECTIVELY NOT FOR PROFITS BIOTECH LOOK AT THE STATS OF WHY THINGS WERE FAILING AND THEN WE WERE ACTUALLY ABLE TO DO SOMETHING ABOUT IT AND DRUGS FAIL MISERABLE FOR REASONS THAT THEY DON'T FAIL ANYMORE, LEAD TO METABOLISM AND FARM CO DINETTICS, AND THEY SAID OKAY WHAT CAN WE DO ABOUT THIS AND THEY THINGS LIKE HER-TWO ASSAYS SO THEY NOW THAT THE REASON AND IN SOME CASES IT'S NOT EVEN JUST IDENTIFYING THE RIGHT TARGET, IT'S UNFORTUNATELY A LITTLE BIT MORE COMPLICATED THAN THAT. SO YOU MIGHT SAY IT'S AN ISSUE OF ROBUSTNESS WHERE I CAN INHIBIT THE TARGET AND HAVE THE DESIRED EFFECT WHICH IS LESS THE ATP PROCESSING BUT I ALSO HAVE THIS ONMECHANISM EFFECT OF YOU KNOW PROCESSING NOTCH BEING DEGRADED. SIMILARLY THERE ARE MECHANISMS GOING IN THE OPPOSITE DIRECTION, WITH PATHWAYS, SO THE MORE YOU UNDERSTAND THE DISEASE AND THE MORE YOU UNDERSTAND THE BIOLOGY THAT YOU'RE TRYING TO MODULATE, THE BETTER POSITION YOU ARE TO GIVE A SET OF MARCHING ORDERS TO A TRANSLATIONAL TEAM WITH THE DESIRED TARGET PRODUCT PROFILE OF THE MOLECULE THAT YOU THINK WILL HAVE THE RIGHT PROFILE FOR CREATING THIS DISEASE OF INTEREST. >> I WOULD LIKE TOAD ONE POINT THAT THAT, WHILE IT'S INTERESTING TO LOOK AT THE PATHOPHYSIOLOGY TO THE DISEASES, YOU HAVE TO KEEP IN MIND THE FOCUS ON WHAT YOUR MECHANISM OF ACTION THAT YOU'RE TARGETING IS AND ALTHOUGH THERE MAY BE IF WE DON'T KEEP FOCUSED ON WHAT IS THE DRUG HIT NOTHING TERMS OF MECHANISM OF ACTION AND BE HARD NOSED ABOUT FOLLOWING THAT THROUGH THE MODELS AND THEN IS WITH THE PATIENTS, I THINK WE WILL END UP GOING DOWN A LOT OF BLIND ALLEYS. >> I WONDER FEDERAL THAT WAS A ONE-OFF PROGRAM FOR RETT, OR SCALABLE TO OTHER DISEASES? AND WALTER YOU ASKED OR POSED A QUESTION EARLIER ABOUT THE OPPORTUNITIES OR ROLES OF PATIENTS AND PATIENT ADVOCACY GROUPS IN THE TRANSLATIONAL RESEARCH STRATEGIC PLAN, I'M WONDER FIGURE THERE'S SPACE THERE FOR THE DEVELOPMENT AND TOOL KITS FOR GROUPS FOR US AT PEER TO PEER MEETINGS LIKE THIS TO HAVE A COOKBOOK TO HELP US FIGURE OUT HOW TO CREATE PROGRAMS TO STANDARDIZE HOW OUR ANIMAL MODELS ARE PHENOTYPES OR WHAT STEPS WE CAN TAKE TO HELP REALLY MAKE MEANINGFUL CONTRIBUTIONS TO MOVING THINGS FROM THE SCIENCE FROM THE BENCH TO THE PATIENT. SNSMGHT IT'S NOT AS SIMPLE AS A FOCUS FOR THE VARIATIONS DEPENDING ON WHAT THE DISEASE IS, AND WHAT THE MOLECULES AND INTERVENTIONS ARE, BUT I THINK A LOT OF THINGS WE'RE TALKING ABOUT TODAY, AND YESTERDAY, COULD BE ADVANCED BY SOME OTHER TYPE OF MECHANISM WHETHER THERE'S A RESOURCE FOR THE NONPROFITS TO KIND OF GET THEIR--THEIR QUESTIONS ANSWERED, OUR PROGRAM DIRECTOR CANS CERTAINLY DO THAT TO A GREAT EXTENT. >> [INDISCERNIBLE]. >> IN REGARD TO THE MODEL THAT WE DEVELOPED FOR PSYCHOGENICS WITH THE HELP OF--AGAIN, WE HIRE THEM AS A CONTRACT RESEARCH ORGANIZATION AND SPECIFICALLY HAD PART OF THE THEME LAURA ASSEMBLED FOR THE WORKSHOP BECAME THE ADVISORY GROUP FOR SETTING UP THAT MODEL. AND SO, THEY SAID, HERE'S--WE'RE GOING TO CHOOSE THIS PARTICULAR MOUSE BECAUSE THERE WERE MANY RAT MICE, MANY DIFFERENT FORMS OF RAT MICE, AND IT'S GOING TO BE TESTED IN THIS MANNER, SO IT'S REALLY A RAT SYNDROME ORIENTED MODEL, BUT THERE'S BEEN A NUMBER OF OTHER NOT FOR PROFITS WHO HAVE TAKEN AS A MODEL, AND ARE WORKING WITH PSYCHOGENICS TO BUILD SOMETHING VERY SIMILAR SO THEY CAN HAVE THEIR MODEL, THAT'S BLINDED, RANDOMIZED, WITH ROBUSTNESS, THAT THEY CAN ESSENTIALLY RUN A SERIES OF DRUGS THROUGH JUST TO SEE, DO THEY WORK, DO HAY NOT WORK IN THIS MODEL AND THEN YOU HAVE TO GO DO ALL THE THINGS THAT ROBERT TALKS ABOUT WITH THAT, BUT THE DRUG COMPANIES ARE HAPPY TO DO THAT IS ESSENTIALLY USING THIS AS A SCREENING PROCESS. BUT IT'S REALLY RETT SPECIFIC THE ONE THAT WE FILL. >> I WANT TO ADDRESS THE QUESTION AND THE POINT YOU JUST MADE, ABOUT A HUGE OPPORTUNITY. WE TALK ABOUT COLLABORATION AND MODELS TO DO THAT AND WHAT WE HAVEN'T DONE IS WE HAVEN'T TALKED ABOUT THE CAPABILITY BUILDING THAT IT TAKES TO ENGAGE IN THOSE COLLABORATIONS. AND I THINK THAT'S WHAT YOUR QUESTION REALLY BUILDS UPON, IS HOW IS THERE A BETTER UNDERSTANDING OF THE DRUG DEVELOPMENT PROCESS ITSELF AND ORGANIZATIONS LIKE THE NIH, CAN PARTNER WITH THE FDA WHO DOES HAVE SOME TRAINING PROGRAMS OUT THERE, FOR ADVOCACY ASSOCIATION, LEADERSHIP TO UNDERSTAND THE DRUG DEVELOPMENT PROGRAM, TO WORK WITH YOU, THE EUROPEAN PATIENT ADVOCACY TRAINING EN--STRATEGIESITUTE, SFICALLY AROUND ISSUES, HOW TO BUILD UP YOUR VALUE PROPOSITIONS AND ENGAGING IN THE SCIENCE, THE TRANSLATIONAL SCIENCE, CLINICAL TRIALS AND DRUG DEVELOPMENT PROCESS. >> TERRIFIC PRESENTATIONS AND A LOT OF LESSONS FOR ALL OF US, SO THANK YOU FOR THAT. WITH TWO REPRESENTATIVES OF INDUSTRY AND THREE FROM THE NONPROFIT COMMUNITY, I WANT TO ASK A QUESTION THAT MAYBE STEVE JUST BEGAN TO ANSWER AND THAT IS YOU'VE SPOKEN AS KITH RIN JUST DID, THE IMPORTANCE OF COLLABORATION BETWEEN INDUSTRY AND NONPROFITS FOR EXAMPLE ABOUT IN THE PRECOMPETITIVE SPACE AND BETWEEN AND AMONG YOUR INDUSTRY PARTNERS AND PARTICULAR NONPROFITS AND MAYBE STEVE WHEN YOU DEVELOPED THIS MOUSE MODEL WITH LAURA'S HELP WITH THE WORKSHOP, THAT WAS DONE WITH VARIOUS DRUG COMPANIES I DON'T KNOW ABOUT THAT, BUT WHAT WOULD YOUR COMMENTS ABOUT ON THE IMPORTANCE OF OR METHOD TO CREATE SOME PRECOMPETITIVE COLLABORATION AMONG YOUR INDUSTRY PARTNERS TO CREATE BIOMARK ORS OR ANIMAL MARKERS THAT WILL BE HELPFUL FOR EVERYONE IN THAT DRUG DEVELOPMENT SPACE. >> I THINK ROBERT HAS PLAYED IN IN SPACE FROM ANYBODY IN THE STAND POINT OF TELLING PEOPLE IF YOU WANT TO COME INTO THIS SPACE YOU HAVE TO CHECK YOUR EGO AT THE DOOR AND BE WILLING TO SHARE, WE NOT ONLY HAD ACADEMICS AND FOR PROFIT REPRESENTATIVES ON THE ADVISORY COMMITTEE BUT THAT WAS I LAID THE GROUND RULES OUT. CHECK IT OUT THE DOOR, WHAT I WANT EVERYBODY TO DO IS TO COME INTO THIS ROOM AND AND THE CHILDREN IS THE WOMEN WITH RETT'S SYNDROME, I DON'T CARE ABOUT THE QUALITY OF LIFE FOR THESE GIRLS AND THAT MEANS EVERYBODY NEEDS TO ECENTSIALLY BRING THEIR BEST GAME FORWARD AND LET'S ACTUALLY SEE IF WE CAN BUILD SOMETHING THAT WILL HELP AND I CAN TELL YOU THAT THE ACADEMICS AS WELL AS THE FORPROFIT PEOPLE WHO ENTERED THE ROOM WERE ABLE TO DO THAT. I COULD BT AGREE MORE. IN FACT, ONE OF THE THINGS, THIS MIGHT SOUND LIKE A NUANCE BUT WE DON'T GIVE GRANTS, WE DO CONTRACTS AND ONE OF THE REASONS THAT IN OUR CONTRACTS WE'RE ABLE TO SPECIFY EXACTLY WHAT WAS JUST SAID, AND I DON'T THINK WE CALL OUT THE THING PER SE BUT FUNCTIONAL WE SAY ENABLING, KNOW-HOW, TOOLS, TECHNOLOGY, MICE, CDNAs, CELL LINES THAT'S ALL PRECOMPETITIVE AND SHARE THAT ACROSS THE COMMUNITY, IN FACT BEYOND THE COMMUNITY AND INTO THE REST OF SCIENCE. YOU KNOW IT'S KIND OF WEIRD TO SEE WHERE PEOPLE DRAW THE LINE OF PRECOMPETITIVE SPACE IS, WHEN YOU THINK ABOUT THE FACT THAT THERE HAVE BEEN COMPANIES THAT ARE WILLING TO MAKE THE 27th HMG REDUCT ACE INHIBITOR, WHETHER OTHER ONES WERE APPROVED FROM'S ALWAYS ROOM FOR COMPETITION LATER AND WE SHOULD THINK ABOUT PARTICIPATING COLLECTIVELY AND SOME OF THE REALLY HARD PROBLEMS, LIKE BIOMARKER DEVELOPMENT AND LIKE TARGET IDENTIFICATION, BECAUSE THEN THIS PLENTY OF OPPORTUNITIES FOR PEOPLE TO CARVE OUT WHAT ULTIMATELY IS REQUIRED WHICH IS THEIR OWN INTELLECTUAL PROPERTY AND THEIR OWN THERAPEUTIC CANDIDATES. >> OKAY IF THERE ARE NO MORE QUESTIONS PLEASE JOIN ME TO THANK ALL THE SPEAKERS. [ APPLAUSE ] WE WILL BE BACK IN HERE IN-- >> NO WE'RE GOING TO THE NEXT PANEL NOW. >> WE GOING STOCK EXCHANGE HAVE LUNCH AT ONE, ARE PEOPLE OKAY WITH THAT? PAINFUL PACES? BUT--ALL RIGHT. GREAT. SO WE CAN TALK SIMILAR--I THINK A LOT OF THINGS LEFTOT TABLE TAKEN--THEY CAN BE BROUGHT UP IN THE BREAK OUT SESSIONS AND I PARTICULARLY THE SUGGESTION THAT MAYBE THERE NEEDS TO BE SOME KIND OF MORE OF AN ONGOING RESOURCE FOR THE NONPROFITS THAT WE COULD POTENTIALLY PUT TOGETHER THAT WOULD BE AVAILABLE THROUGHOUT THE YEARS AS OPPOSE TO JUST THE CONFERENCES. >> OKAY, SO THE NEXT SESSION, LAST SESSION IS PARTNERING EFFECTIVELY WITH INDUSTRY AND CLINICAL TRIALS. AND THE MODERATORS, ELIZABETH McNEAL AND CYNTHIA ROTHPLUM-OI HAVE IATT, AND CATHERINE BEAVERSON, AND HUBERT FERNANDEZ, PROFESSOR OF MEDICINE AT CLEVELAND CLINIC WORKING WITH THE PARKINSON'S GROUP, AND JIM KISER IS A MEDICAL OFFICER AT THE FDA AND SERVES AS A LEAD FOR THE CENTER'S CRITICAL PATH INNOVATION MEETING. SO WE APPRECIATE THE GROUP COMING DOWN AND WE GET STARTED. I'M STANDING BETWEEN YOU AND LUNCH. WE WILL GET STARTED, HAVE SHORT INTRODUCTIONS AND WE WILL MOVE THINGS ALONG. THERE'S ACTUALLY NO FLUID BOUNDARIES BETWEEN TRANSLATIONAL AND CLINICAL AND I WOULD LIKE TO REITERATE THAT FROM THE LAST PANEL. I WOULD LIKE TO KNOW ABOUT KNOWING THE D-TECHS WITH TRANSLATIONAL IS NOT ENOUGH. YOU NEED TO KNOW THAT HAVING THAT IDENTIFIEDED DEFECT CAUSES THE SIGNS AND SYMPTOMS THAT A PATIENT IS SEEING AND YOU NEED TO KNOW THE EFFECTS OF AMELIORATING THOSE DETECTS OF WHETHER IT'S COMPLETE REVERSAL OF THE PROBLEM OR PARTIAL REVERSAL OF THE PROBLEM AND THAT'S SOMETHING YOU DON'T ALWAYS KNOW--OI'M FROM NEW YORK, I DIDN'T REALIZE I WAS THAT SOFTSPOKEN. TURN OFF YOURS THEN. THERE WE GO, WE SHARE THEM, HE'S FROM BROOKLYN. THE OTHER BURRO, ANYWAY. >> FIGHTING WORDS THERE, WELL SINCE YOU'RE MY BOSS, WE CAN'T FIGHT, I'LL DEFER JUST FOR TODAY THOUGH. [LAUGHTER] ANYWAY, SO WE HERE AT N INDS, WORK ON THIS, THINK ABOUT A LOT HOW IT IS THAT WE'RE GOING TO INVOLVE THE PATIENTS WE'RE TRYING TO WORK WITH AS WELL AS INDUSTRY ACADEMIA AND ONE OF THE WAYS WE DO THAT, YOU HEARD WALTER TALK ABOUT YESTERDAY, THE 25 GIVING--YOUOGRAPHICALLY DISTRIBUTED SITES IN THE U.S., AND ONE OF THE THINGS WE REALLY WORK ON WITH NEURONET SYSTEM RARE DISEASES BECAUSE WE THINK WE'RE PARTICULARLY WELL POSITIONED TO DO THAT. WE ACTUALLY WORK WITH INDUSTRY AS WELL AS ADVOCACY BECAUSE ALL OF THE NEURON EXPECTATIONS PROJECTS EVERY SINGLE ONE OF THEM, WE INSIT CYST THAT THE PIs, WORK WITH PATIENTS OR CAREGIVERS OR PATIENTS WITH THAT DISEASE. FROM THE VERY BEGINNING. THEY HELP US WRITE THE PROTOCOLS. THEY SERVEOT PROTOCOL STEERING COMMITTEE FOR GRANTS THAT ARE FUNDED AND THEY SIT ON THE DATA SAFETY MONITORING BOARDS. SO FOR THE ENTIRE PROCESS, THEY'RE INVOLVED AND WE HAVE FOUND THAT THAT HAS BEEN A TRUE BENEFIT. ONE THING THAT ADVOCACY CAN INFORM FOR OUR PROJECTS AND HAVING ADVOCACY AT THE TABLE, HELPS US KNOW SOMETHING ABOUT NATURAL HISTORY, AND POTENTIAL THINGS THAT THE FAMILIES OR THE PATIENTS KNOW IS ACTUALLY A PART OF THEIR DISEASE AND IS NOT AN ADVERSE EVENT THAT IS RELATED TO THE INVESTIGATIONAL AGENT IS KEY INFORMATION TO GIVE TO PEOPLE EARLY ON, KNOWING THAT ADVOCACY CAN TELL US ALSO WHAT'S IMPORTANT TO PATIENTS, WHAT TYPE OF BENEFIT THEY THINK IS WORTH IT FOR THE RISK THATTARY BEING ASKED TO UNDERTAKE AND TAKEN--THEY'S IMPORTANT FOR THEM TO CONVEY TO INDUSTRY, BECAUSE IT SUGGESTS HOW WE'RE GOING TO DESEEN THIS AND WHAT WE'RE GOING TO LOOK FOR, THE OTHER THING THAT'S BEEN HELPFUL FOR US IS NEURONET SYSTEM PROVIDING AND I CAN SAY THIS, PROVIDING FUNDS SOPHISTICATED TRY TO HELP EXPAND OUR STUDIES. FOR EXAMPLE, WE'RE DOING A MULTIPLE SCLEROSIS STUDY, WE'RE ORIGINALLY GOING TO HAVE 22 SITES, THE NATIONAL MULTIPLE SCLEROSIS SITES SAID NO WE WANT TO YOU EXPAND THAT BECAUSE WE HAVE A LOT OF PATIENT WHO IS ARE INTERESTED IN PARTICIPATING, ADD ON SIX SITES AND WE'LL HELP YOU PAY FOR IT. SO THE INDUSTRY PARTNER WAS PUT NOTHING MONEY BECAUSE THEY'RE CO FUNDING THIS WITH THE NINDS AND THEY SAID OKAY HA CAN WE DO TO MAKE SURE THAT A WIDER SWATH OF OUR CONSTITUENCY CAN HAVE A CHANCE TO PARTICIPATE IN THESE STUDIES. SO THAT WAS DONE AS I SAID A NATIONAL MULTIPLE SCLEROSIS SOCIETY, ALONG WITH INDUSTRY PARTNER, AND ACADEMIA, AT CLEVELAND CLINIC IS THE WAY THE PIs HOUSE FOR THAT STUDY. IT'S BEEN ENKRIDLELY SUCCESSFUL HAVING ADVOCACY COME TO THE TABLE AND WORK WITH US EARLY ON HAS, I THINK BENEFITED ALL FIVE OF THE NEURONET STUDIES WE HAVE ONGOING AT THIS TIME. I LIKE TO THINK IT'S ONE OF THE BETTER THINGS THAT WE'VE DONE IN SETTING UP ONE OF OUR NINDS NETWORKS WITH THAT I'M GOING TO QUICKLY TURN IN THE INTEREST OF TIME TO TALK TO THE REST OF THE PANEL AND HAVE THEM TALK ABOUT SOME OF THE WAYS THAT THEY SEE, ADVOCACY CAN WORK WITH INDUSTRY TAKING CLINICAL TRIALS FORWARD. THE FIRST PERSON I'M GOING TO INTRODUCE DOES NOT HAVE A SHEET HERE BUT SHE'S CYNTHIA, SITTING RIGHT NEXT TO ME AND THE DOCTOR IS SCIENCE CORDINATOR FOR THE ATAXIA CHILDREN'S PROJECT, AND SHE'S GOING TO ACTUALLY ALSO TELL YOU ABOUT SOMETHING ELSE SHE'S DOING BECAUSE SHE'S DOING A FAVOR FOR A PANELIST WHO COULDN'T BE HERE TODAY. >> OKAY, SO IT'S MY PRIVATE SECTOR EDGE TO BE HERE TODAY TO NOT TALK ABOUT ATAXIA BUT TO SPEAK ON BEHALF OF THE HEMPEL FAMILY AND SHARE THEIR STORE WEB CONNECTED YOU TODAY. SO FROM MY OWN EXPERIENCE WORKING WITH A RARE DISEASE ADVOCACY ORGANIZATION AS WELL AS FROM TAKING A DEEP ARE DIVE INTO THE HEMPEL FAMILY STORY AND LEARNING ABOUT THEIR JOURNEY, I THINK I CAN SAY THAT WHEN URGENCY, AND I'M TALK ABOUT THIS URGENCY THAT YOU FIND WITH PARENTS AND FAMILIES SEEKING ANSWERS, WHEN URGENCY NEEDS SCIENCE, IT'S NOT ALL THIS AND AS A MATTER OF FACT IT MAY BE THIS, AND THERE'S ALWAYS THIS. AND THE COMMON GOAL OF FINDING LFE AND IMPROVING THERAPIES AND CURES FOR TREATING DISORDERS. SO THE HEMPEL IS NOT A JUST A STORY ABOUT A BALANCE BETWEEN URGENCY AND SCIENTIFIC RIGOR, AND ALL OF THIS MAY NOT COME OUT IN THE SHORT AMOUNT OF TIME THAT I HAVE TO SHARE THEIR STORY BUT IT'S ALSO A BALANCE BETWEEN RISK AND BENEFIT AND A BALANCE BETWEEN ACTION AND INACTION. AND THE HALFLE STORY IS ACTUALLY KIND OF ONE OF AN UNCONVENTIONAL ROUTE TO CLINICAL TRIALS FOR A GENETIC DISORDER. SO I'M GOING TO CONDENSE A BIG STORY AND A VERY SHORT AMOUNT OF TIME AND I HOPE THAT THIS SLIDE HELPS AS I FLY THROUGH THIS, BUT IN 2004, HUGH AND CHRIS HEMPEL HAD TWIN DAUGHTERS ADDIE AND CATHY AND WHEN THE GIRLS WERE THREE YEARS OF AGE THEY OTHER THAN DIAGNOSED WITH NPC, CHARACTERIZED BY A BUILD UP OF CHOLESTEROL AND COMPLEX LIPITTEDS AND FATS IN CELLS AND TERMS OF THE BRAIN THIS MEANS PROGRESSIVE NEURODEGENERATION SO CHRIS AND HUBERTER BOTH PEOPLE OF ACTION SO AFTER THE DIAGNOSE THEY SPENT A LOT OF TIME ONLINE LOOKING TO FIND OUT WHAT'S KNOWN ABOUT NPC AND WHAT RESEARCH WAS BEING DONE AT THAT TIME. AND THEY CERTAINLY FOUND THAT A LOT OF BASIC SCIENCE RESEARCH WAS BEING PERFORMED BUT LITTLE TO NOTHING WAS HAPPENING IN TERMS OF REAL LE A SEARCH FOR TREATMENT AND SO LATER THAT YEAR, STILL IN 2007, A PAPER WAS PUBLISHED BY A GROUP OF SCIENTISTS THAT DEMONSTRATE THAD A SINGLE INJECTION OF A DOSE OF A SUGAR COMPOUND COULD SIGNATURES FIVE CANTILY EXTEND THE LIFE SPAN OF A MOUSE MODEL WITH PNEUMONIC TYPE-C, SO CHRIS AFTER SEE THANKSGIVING IS SEEING LITTLE ELSE IDENTITY ON THE HORIZON AND AFTER TRYING IT HERSELF, CHRIS HEMPEL IN EARLY 2008 BEGAN TO GIVE HER TWINS POWDERED CYCLODEXTRIM MIXED INTO THEIR DRINKS AND THE SCIENTISTS AT THAT TIME WERE LESS IMPRESSED AND THAT THOUGHT YOU COULDN'T GET ENOUGH INTO THE BRAIN TO MAKE A DIFFERENCE AND THEY WERE NOT DISSUADED BY THAT IN DECEMBER 2008 ALONG WITH THE TWIN'S DOCTORS THEY APPROACHED THE FDA THEMSELVES TO GET PERMISSION TO GIVE CYCLODE XTRINE, BUT BEFORE THEY COULD GRANT THAT APPROVL THEY REQUIRE SAFETY DATA SO THROUGH ONE OF HER CONTACTS ALONG THIS WAY AND PRT OF HER JOURNEY, CHRIS HAD LEARNED THAT THERE WAS A COMPANY OWNED BY JOHNSON AND JOHNSON THAT HAD DEVELOPED CYCLODEXTRIN AS AN ANTIFUNGAL AGENT SO THEY HAD THE SAFETY DATA ON PSYCHE LOW DEXTRIN AND WHEN HE CALLED THEM. THE COMPANY DENIED HER REQUEST TO SHARE THE SAFETY DATA WITH THE FDA, BUT AGAIN TO BE A PERSON OF ACTION AND NOT DETERRED BY THIS, CHRIS HIT THE WORLD WIDE WEB WITH A BLOG ENTITLED DEAR JOHNSON AND JOHNSON, DO KIDS REALLY MATTER TO YOU? AND SHE ALSO CALLED THEIR PR DEPARTMENT JUST TO MAKE SURE THEY GOT THAT MESSAGE. SO THE FDA GAINED ACCESS TO THE SAFETY DATA THEY NEEDED FOR PSYCHODEXTRIN AND THEY SUBSEQUENTLY APPROVED THE INTRAVENOUS INFUSION FOR THE TWINS. SO IT'S AT THIS POINT THAT THE HEMPEL SUBJECT ONE JUST ABOUT THEM HELPING THEIR CHILDREN, BUT THIS IS ALSO A STORY ABOUT HOW THEY PARTNERED WITH OTHER FAMILIES IN THE NPC COMMUNITY AS WELL AS SCIENTISTS WHO HAD BEEN STUDYING THIS DISEASE FOR YEARS AND THE NIH. AND THIS BROADER COLLABORATION OR PARTNERSHIP ALSO BEGAN VERY EARLY ON IN 2007 WITH A MEETING HERE AT THE NIH WHICH WAS ORGANIZED BY CHRIS AUSTIN WHO WAS AT THE TIME DIRECTOR OF THE NIH CHEMICAL GENOMIC CENTER, SO THIS MEETING BROUGHT TOGETHER, SCIENTIST, PARENTS AND THE NIH. AND THIS BROADER COLLABORATION LED TO ULTIMATELY AN FDA APPROVED NIH CLINICAL TRIAL OF PSYCHE LOW DEXTRIN AND FOR THE TRIAL AND ALSO FOR FAMILIES OF INDEPENDENTLY SEEKING FDA PERMISSION TO GIVE THEIR CHILDREN PSYCHE LOW DEXTRIN. --CYCLODEXTRIN. SO MAYBE AN UNUSUAL START TO PARTNERSHIPS WHO ARE ADVOCATES PARTNERING WITH SCIENTISTS, WITH THE FTA AND WITH INDUSTRY, THE FDA, HAS APPROVED ORPHAN DRUG STATUS, FOR CYCLODEXTRIN AND WHEN THE HEMPEL'S IN 20 TAKEN THEY 20 TO SEEK THIS ORPHAN DRUG STATUS, THEY DID SO WITHOUT AN INDUSTRY PARTNER, FORMER TRIALS OF CYCLODEXTRIN FOR NPC WERE START INDEED IN JANUARY OF THIS YEAR, THE NIH ANNOUNCED A COLLABORATION WITH A SMALL BIOTECH, Z-TEP TO DEVELOP NEW DRUGS INCLUDING AND WITH OTHER LYSOSOMAL STORAGE DISORDS. SO WITH THAT I WILL END. >> WE'LL MOVE ON TO DR. PERNANOG DEZ, THANK YOU WHO IS COMING TO US FROM CLEVELAND CLINIC. HE'S A PROFESSOR OF NEUROLOGY AT CLEVELAND CLINIC'S LEARNER COLLEGE OF MEDICINE AND THE HEAD OF MOVEMENT DISORDERS UNDER THE DURATION OF CLEVELAND CLINIC. >> THANK YOU VERY MUCH FOR--HELLO? GOOD. THANK YOU ARE MUCH FOR INVITING ME, I WAS GIVEN--TOLD TO SPEAK FOR FIVE MINUTES NO MORE SO I WILL TRY TO SPEAK FOR SEVEN. SO FORTUNATELY, YOU KNOW MY AREA OF EXPLORATION, PARKINSON'S DISEASE IS MUCH MORE COMMON THAN NPC, THERE ARE 1.5 MILL YEN PARKINSON'S PATIENT ON OUR CONTINENT SO THERE ARE LOTS OF PEOPLE WORKING ON PARKINSON'S DISEASE AND IT'S--WE'RE FORTUNATE TO TAP ON THOSE RESOURCES AND A LOT OF PEOPLE VERY INTERESTED INDUSTRY, NOT FOR PROFIT OR ORGANIZATIONS, THE NIH, AND OTHER--OTHER ENTITIES, BUT THIS IS ONE MODEL THAT I THINK WE JUST--WE STUMBLED UPON AN OPPORTUNITY WAS GRANTED TO US, 28 YEARS AGO AND THAT I THINK HOPEFULLY WILL INSPIRE OTHER DISORDERS AND GIVE AT LEAST AN OPTION OF A MODEL TO GROW YOUR DEVELOPMENT OF YOUR PARTICULAR FIELD IN WAYS OF PARTNERING NOT ONLY WITH INDUSTRY, BUT WITH ALL OTHER SECTORS THAT ARE INTERESTED IN THE SAME FIELD. SO THE PARKINSON'S STUDY GROUP IS AT LEAST NORTH AMERICA'S LARGEST PROACTIVE NOT FOR PROFIT SCIENTIFIC NETWORK OF PARKINSON INVESTIGATORS. WE HAVE BEEN IN EXISTENCE FOR 28 YEARS NOW. THIS WAS STARTED 28 YEARS AGO, A GRANT GIVEN TO IRA SCHOLZEN, TO INVESTIGATOR THE NEUROPROTECTIVE OR DISEASE MODIFYING EFFECTS OF CELEDULINE IN PARKINSON'S DISEASE. AND WHILE--BETH COMPOUNDS CEDULIN AND VITA MINE E THERE'S A LOT OF GOOD THAT CAME OUT OF THAT INITIAL FEED PROJECT FROM THE NIH. SO, WE PRIDE OURSELVES, PARKINSON'S STUDY GROUP LARGEST NOT FOR PROVIC SCIENTIFIC NETWORK OF SPECIALISTS IN OUR CONTINENT TO DELIVER COMPREHENSIVE, YOU KNOW SERVICE FOR A SUCCESSFUL CLINICAL TRIAL DEVELOPMENT SO FROM THE PLANNING WE HAVE ABOUT 250 CREDENTIALS INVESTIGATORS AND THOUGHT LEADERS IN THE AREA OF PARKINSON'S DISEASE, WE'VE PARTNERED WITH OUR MAIN PARTNER FOR RESEARCH ORGANIZATION IS THE CTCC AT THE UNIVERSITY OF ROCHESTER, NOW EXPANDED TO A SECOND ARO AS WELL FOR DIFFERENT REASONS OR DIFFERENT SPECIALTIES WITH THE MGH, NCRI AS A--AS A SECOND ACADEMIC RESEARCH ORGANIZATION AND OF COURSE, THE--WE--WE GO THROUGH IT, AND THE MOST IMPORTANT PART FOR US, IS DISSEMINATING THE RESULTS AND PRESENTING THEM AND PUBLISHING THEM WITH THE HIGHEST SCIENTIFIC RIGOR. SO THE PSG CAN BE A PARTNER OF AN INDUSTRY OR ANY PHARMACEUTICAL COMPANY FROM THE BEGINNING TO THE EXECUTION UNTIL YOU KNOW SIDE BY SIZE FDA DEFENDING THE DRUG IF NEED BE AND THIS HAS BEEN OUR WAY WE'VE DONE THINGS ALL ALONG. SO THIS WAS IN BLACK AND WHITE, 1987 WHEN A GROUP OF INVESTIGATORS WAS FUNDED BY THE NINDS TO STUDY CEDULINEAND STUDY WHAT IT COULD DO IN PARKINSONS AND MORE AND MORE STUDIES AND BIGGER AND BIGGER MEMBERS BEING ADDED ON. NOW WE HAVE ABOUT 250 INVESTIGATORS FROM NORTH AMERICA LOCATED IN ABOUT A HUNDRED 30 TO 140 CLINICAL TRIAL CENTERS INCLUDING HAWAII AND PUERTO RICO AND EIGHT CENTERS IN CANADA AND THE MAJORITY IN THE UNITED STATES. OUR GIDDING PRINCIPLES ARE THE ONES WE BELIEVE SET US APART AND KEEP THE LOYALTY OF THE MEMBERS OF THE PARKINSON'S STUDY GROUP. SO ONE IS THE DEMOCRATIC GOVERNANCE SO EVERYONE HAS ONE VOTE. WE VOTE OUR LEADERS WE VOTE OUR CO CHAIRS, I HAD TO RUN FOR THE CO CHAIR, FOR THE CHAIR AND CO SHARE POSITION, IT'S A TICKET LIKE, YOU KNOW DEMOCRATIC TICKET AND REPUBLICAN TICKET, YOU CAN MIX AND MATCH AND YOU HAVE TO VOTE, YOU KNOW ONE PARTY, I SUPPOSE. AND SO, WE ELECT OUR LEADERS AND ALSO WHEN WE HAVE A CLINICAL TAL COMING ALONG WE HAVE--WE HAVE TO SURVEY ALL 132 CLINICAL TRIAL CENTERS, JUST ASK FOR INTEREST, IN PARTICIPATING FOR THAT CLINICAL TRIAL AND WE HAVE THE SAME QUESTIONNAIRE, WE GIVE VIA E-MAIL TO ALL 138--32 SITES. AND THEY TRY TO ANSWER THE QUESTIONS AS BEST THEY CAN IN A DEMOCRATIC SELECTION PROCESS, WE GET HOWEVER MANY SITES WE NEED, THE 30 BEST, 40 BEST, 10 BEST OR THE 20 BEST. SO EVERYONE KNOWS WHAT EVERYONE'S GOING, WHAT EVERYONE'S DOING AND EVERYONE HAS A CHANCE TO MAKE A BID FOR IT. NOT MUCH OF AN OLD VOICE NETWORK. WE PRIDE OURSELVES ON RIGOR AND ETHICS IN CONDUCTING CLINE TRAIL TRIAL. WHEN YOU DO SOMETHING FOR THE INDUSTRY, OBVIOUSLY YOU'RE CONFLICTED. THEY'RE PAYING YOUR SALARY OR YOUR STAFF SALARY AND YOU WOULD LIKE TO PRESENT AS GOOD A RESULT AS POSSIBLE. BUT WE TRY OUR BEST TO TRY TO BE ABOVE THAT, EVEN. NONE OF OUR--NONE OF US ARE ALLOWED TO TAKES ANY PERSONAL COMPENSATION FOR ANY--AT LEAST DURING THE ENTIRE TRIAL, UP TO THE PUBLICATION DATE OF THAT, FOR SPEAKER'S BUREAU OR CONSULTING OR ANYTHING LIKE THAT, OR EVEN THE COMPETITORS OF WHAT WE'RE DOING, SO, SO WE HAVE THAT. AND THEN, WHEN WE ANALYZE THE DATA, WE HAVE ACCESS TO THE COMPLETE DATA SET, THE RAW UNFETTERED DATA SET AS OPPOSE TO JUST A SUMMARY, OF THE CLINICAL STUDY REPORT. AND EVERYONE IS A CO-AUTHOR OF THE PARKINSON'S STUDY GROUP CLINICAL TRIAL. ALL THE INVESTIGATORS, ALL THE COORDINATORS, AND ALSO REPRESENTATIVES OF THE COMPANY, THE STATISTICIANS ALL STAY IN ONE ROOM AND IF THERE'S NO MONEY, NOT MUCH MONEY LEFT, THEN IT'S GOING TO BE A WEB EXPECTATIONS OR SOME TELECONFERENCE AND THEN WE--THE STEERING COMMITTEE WRITES THE FIRST DRAFT AND WE--WE BASICALLY AGREE ON EVERY PARAGRAPH AFTER PARAGRAPH, AND SO, IT IS, YOU KNOW PUBLISHED WITH THE HIGHEST SCIENTIFIC RIGOR AND ETHICS. WE'RE PRETTY TRANSPARENT, THE ONE BEAUTY OF GOING THROUGH THE PARKINSON'S STUDY GROUP IS THAT WE HAVE A UNIFORM PERSUBJECT FEE FOR ALL OF OUR SITES REGARDLESS OF THEIR LOCATION, AND SO WHEN THEY--WHEN THE COMPANY PARTNERS WITH US WITH A HANDSHAKE, OKAY, IT'S GOING O BE WHATEVER, $7000 PER SUBJECT INCLUDING INDIRECT, IT'S GOING TO BE THE SAME FEE FOR ALL--FOR ALL SITES. SO THERE IS NO NEGOTIATION AND BACK AND FORTH. AND SITES LIKE THAT, THAT THE CENTRAL, YOU KNOW LEADERSHIP OF THE TSG ALREADY DEALT WITH THAT AND WHAT IS A FAIR PRICE OF THEM AND THEY DON'T NEED TO BE PARAINOID THAT ONE SIDE GOT MORE MONEY THAN THE OTHER. SO THESE ARE OUR GIDDING PRINCIPLES AND TO DATE WE HAVE OVER 40 CLINICAL TRIALS THAT, WE HAVE SUCCESSFULLY COMPLETED ONTIME, ON BUDGET AND FOUR OF THESE COMPOUNDS A LOT OF THEM FROM INDUSTRY AND FOR OF THESE COMPOUNDS ARE NOW SUCCESSFUL FDA PRODUCTS BEING USED BY PARKINSON PATIENTS. THE POWER OF SHARING THE DATA AND HAVING 250 THOUGHT LEADERS AND PARKINSON'S DISEASES IS THAT WE JUST--WE DON'T STOP PUBLISHING THE PIVOTAL TRIAL, WE DATA MINE FOREVER AND EVER AND AS CAN YOU SEE HERE, THE FIRST STUDY, THE DATA TOP STUDY, THE ONE FUNDED BY THE NIH, IT WAS THE ORIGINAL FIRST STUDY, 46 PUBLICATIONS AND GROWING. SO IT'S--IT'S THE GIFT THAT KEEPS ON GIVING FOR THE PARKINSON'S STUDY GROUP SO BY JUST PARTNERING WITH A PSG, WE QUADRUPLE YOUR PUBLICATION RATE AS OPPOSE TOOON INDUSTRY DOG IT BY THEMSELVES. THEY PROBABLY PUBLISHED TWO, THE PIVOTAL AND OPEN LABEL EXTENSION BUT WE WILL PUBLISH MORE THAN THAT AND INCREASE THE IMPACT OF WHAT THAT DRUG DOES. YOU CAN THINK ABOUT A CLINICAL TRIAL LIFE CYCLE STARTING WITH A CONCEPTUAL PHASE AND IF YOU'RE IN THE INDUSTRY, YOU COULD HIRE A CONSULTING COMPANY AND YOU CAN SOLICIT, GATHER YOUR ADVISORS FOUR OR FIVE ADVISORS THAT YOU PAY FOR TO GO INTO ONE AIRPORT HOTEL, AND PLAN THE STUDY. AND THEN GO TO THE PLANNING PHASE, YOU GATHER THEM AGAIN AND YOU PAY THEM. YOU COULD DO THAT AND THEN FOR THE IMP LENS LENS LENS LENSATION PHASE, YOU COULD HIRE AN EVENT PLANNER, TO GATHER, TO ORGANIZE INVESTIGATOR'S MEETING AND HIRE YOUR OWN CRO FOR EXECUTING THE STUDY AND THEN THE ANALYSIS PHASE, YOU MAY OR MAY NOT HAVE YOUR OWN BIOSTATISTICIAN AND THEN YOU GATHER BACK YOUR STEERING COMMITTEE TO HELP YOU WRITE THE PAPER AND MAYBE EVEN HAVE A MEDICAL RIGHTER, WRITER MAYBE NOT WRITE THE PAPER BUT HELP WITH FOOT NOTES AND WHAT NOT MAKING IT NICE. AND THEN YOU PUBLISH IT: SO THIS HAS BEEN ONE WAY AND THIS IS THE TRADITIONAL WAY OF HOW INDUSTRY HAS DONE THE LIFE CYCLE WITH THE PSG MODEL, YOU CAN PARTNER WITH THE PSG FOR ALL OF THESE FACES OR SOME OF THESE PHASES, SOME OF THEM MAY WANT TO ASK FOR OUR REALLY UNBIASED OPINION, WHETHER THIS DRUG IS WORTH PURSUING AS A CONSUPTUAL AND PLANNING PHASE, BUT THEN THEY DO IT ON THEIR OWN FOR THE IMPLEMENTATION AND OTHERS, REELINGLY HAVE THEIR OWN INHOUSE PEOPLE FOR THE CONCEPTUAL PHASE, THEY USE THE PSG FOR THE PLANNING AND IMPLEMENTATION AND PUBLICATION PHASE. SO THAT'S WHAT THE THEY OFFER THE INDUSTRY. THANK YOU VERY MUCH. [ APPLAUSE ] >> [INDISCERNIBLE]. . >> THANK AND YOU THANKS TO NINDS FOR INVITING ME. I GUESS I DON'T HAVE A GOOD TITLE SLIDE. I'M JIM KISER I'M A MEDICAL OFFICER, I WORK IN THE CENTER FOR DRUG EVALUATION AND RESEARCH AND THEIR OFFICE OF TRANSLATIONAL SCIENCES, I AM THE SCIENTIFIC LEAD FOR THE CRITICAL PATH INNOVATION MEETING AND THE PURPOSE OF MY TALK TODAY IS TO TELL YOU ABOUT THIS RESOURCE WHICH IS NOW BECOMING VERY AVAILABLE TO FROM ALL WALKS OF THE WORLD AND I'LL GO A BIT OFF TOPIC AFTER I TELL BUT THAT TO PUT IN A PLUG OF CERTAIN ASPECTS OF RARE DISEASE DRUG DEVELOPMENT. THIS WAS AN INITIATIVE ROLLED OUT IN 2004, BUT IT'S UNDERWAY FOR A COUPLE OF YEARS NOW AND IT'S GETTING NOR TRACTION AND MORE PEOPLE ARE COMING. SO THIS IS ABOUT CHALLENGES IN DRUG DEVELOPMENT, SO THERE ARE MANY CHALLENGES IN DRUG DEVELOPMENT, AND FDA IS INTERESTED IN TALKING WITH THE COMMUNITY, TALKING WITH DRUG DEVELOPERS, RESEARCHERS AND SO FORTH TO GET YOU ON THE RIGHT TRACK TO HELP YOU UNDERSTAND FDA'S POINT OF VIEW AND WE WILL ALSO GET TO KNOW MORE ABOUT THE INNOVATIONS IN THE FIELD. SO JUST TO ANTICIPATE A LITTLE BIT, WE DO HAVE A GUIDANCE, THESE TOPICS ARE IN THE GUIDANCE AND YOU DON'T HAVE TO WRITE THEM DOWN. I THINK YOU ALSO HAVE YOUR SLIDES. SO ANYWAY, THE TOPICS THAT ARE LISTED IN THE GUIDANCE BUT IT'S NOT EXCLUSIVELY LIMITED TO THESE AND I REMEMBER, WE WERE TALKING ABOUT BIOMARKERS EARLIER, BUT THESE ARE POTENTIAL BIOMARKERS THAT MAY BE IN A MORE RESEARCH PHASE THAT ARE NOT READY FOR THE DRUG DEVELOPMENT TOOL QUALIFICATION PROGRAM. I GUESS THAT'S A BIT OF JARGON, I DON'T KNOW IF YOU KNOW MUCH ABOUT THE QUALIFICATION PROCESS. I CAN TELL YOU ABOUT THAT EITHER AFTER THIS MEETING OR IF THERE'S CONTACT INFORMATION, CAN YOU CALL ME. SO ANYWAY, THE CALLIFICATION PROCESS IS TO MAKE A BIOMARKER AVAILABLE TO DRUG DEVELOPMENT GENERALLY. BIOMARKERLESS ARE USED IN DRUG DEVELOPMENT PER PRODUCT, PER SPONSOR, BUT THIS IS TO MAKE THEM GENERALLY AVAILABLE FOR PEOPLE THIS THAT DISEASE FIELD. ALSO ANOTHER TOPIC WE COVER IS CLINICAL OUTCOME ASSESSMENTS AND THESE ARE MORE PATIENT REPORTED, CLINICIAN PREPORTED, PERFORMANCE AND OUTCOME MEASURE THINGS, THERE'S ALSO GUIDANCE ON CLINICAL OUTCOME ASSESSMENTS, I ONLY HAVE FIVE MINUTES, CAN YOU LOOK THAT UP, TOO. VERY IMPORTANTLY ESPECIALLY FOR THE SECOND PAROF MY TALK, WE WILL TALK TO ORGANIZATIONS WHO ARE JUST GETTING STARTED ABOUT NATURAL HISTORY STUDY DESIGNS AND IMPLEMENTATION. THIS IS A VERY, VERY IMPORTANT THING TO PUT IN THE MIX ESPECIALLY SINCE WE ALL TALKED ABOUT TRANSLATIONAL PIECE, NATURAL HISTORY STUDIES DESIGNS AND IMPLEMENTATION ARE VERY IMPORTANT. ANOTHER TOPIC IS EMERGING TECHNOLOGIES OTHER THAN MANUFACTURING TECHNOLOGIES FOR DRUGS AND BIOLOGICS OR NEW USES OF EXISTING TECHNOLOGIES, SOME OF THESE TECHNOLOGIES MAY BE RELATING TO IDENTIFYING AND USING BIOMARKERS FOR EXAMPLE. AND THEN FINALLY NOVEL CLINICAL TRIAL DESIGNS AND METHODS, WHICH MAY BE OF IMPORTANCE FOR RARE DISEASE BUT IT'S IMPORTANT THROUGHOUT THE SIZE AND SCOPE OF A DRUG DEVELOPMENT PROGRAM. SO, TO ALLAY FEARS ABOUT WHAT HAPPEN WHEN IS YOU INTERACT WITH THE FDA, I THINK PEOPLE MAY HAVE AN IDEA THAT WHAT YOU SAY TO THE FKA, THE FDA WILL WRITE DOWN AND HOLD YOU TO IT, AND SIMILARLY, WE WANT TO AVOID AN IMPRESSION AT THESE MEETINGS THAT THESE UPPER LEVEL DISCUSSIONS ARE GOING TO BE SOMETHING THAT ARE IN THEIR PARTICULARS THAT THEY CAN'T CONTROL THAT WOULD BE BINDING ON US, BUT THE MEETINGS ARE UPPER LEVEL, AND THEY'RE NOT BINDING ON YOU, ON US. AND THAT'S MEETINGS DO NOT SUBSTITUTE FOR DRUG DEVELOPMENT PATHWAY MEETINGS THAT PEOPLE MAY HVE WHO HAVE A DRUG WHO TALK TO THE INDIVIDUAL REVIEW DIVISIONS AT THE FDA. NOW, I DON'T KNOW IF REVIEW DIVISION IS A TERM OF OUR JARGON BUT THE CDER HAS AN OFFICE OF NEW DRUGS AND THE OFFICES WITHIN THE OFFICE OF NEW DRUGS ARE ORIENTED BY DRUG AREA, AND THERE'S DIVISION OF NEUROLOGICAL PRODUCTS THAT'S WITHIN OMD AND THE PRIMARY RESPONSIBILITY IS TO EVALUATE NEW DRUGS AND APPLICATIONS AND LOOK AT APPROVAL PACKAGES THEY'RE VERY OPEN TO THE COMMUNITY SO IT'S NOT AS THOUGH THAT'S THE ONLY THING THEY DO, BUT THE CRITICAL PATH TO INNOVATION MEETING IS NOT INTENDED TO SUBSTITUTE FOR THOSE KINDS OF DISCUSSIONS. IS THIS RIGHT? NO? OOPS. THERE YOU GO. >> SO YES, AS I SAID BEFORE, THE REQUESTS FOR SUCH A MEETING AND I'LL GO THROUGH PROCEDURE LATER, THEY CAN COME FROM A ROLE OF ANYONE WITH DRUG DEVELOPMENT AND I THINK I TOUCH OFFICE OF DIVERSITY THIS VERY BRIEFLY, DID THESE ADVARMIS COSY ORGANIZATIONS, NONPROIOF THES WOULD BE IN THERE, PUBLIC, PRIVATE PARTNERSHIPS, INDUSTRY, ACADEMIA, GOVERNMENT, YOU NAME IT, IF THE TOPIC IS CORRECT WITHIN SCOPE, WE CAN EVALUATE IT AND DECIDE IF IT'S A GOOD TOPIC FOR A MEETING AND THE FDA EXPERTS WE SOLICIT THE--I MAY BE THE SCIENTIFIC LEAD BUT I'M NOT THE EXPERT AND I'M NOT EYE NEUROLOGIST, EVEN, I'M A PULMONOLOGIST. SO WE SOLICIT THE PARTICIPATION OF EXPERTS FROM THE FDA, WHO DON'T HAVE TO COME FROM CDER, THEY MAY COME FROM THE CENTER FOR BIOLOGICS AND THEY MAY COME FOR THE CENTER FOR RADIOLOGIC AND HEALTH SO THAT'S NOT UNUSUAL AND WE CAN GET PEOPLE FROM CENTERS, FROM VARIOUS DIVISIONS WITHIN OMD, AND SO FORTH. SO TO QUALIFY FOR A MEETING, IT REALLY HAS TO BE VETTED SO IT HAS TO COME THROUGH MY OFFICE. SO THE ADVANCE MATERIALS ARE BRIEF, THEY ARE UPPER LEVEL SESSIONS, WE DON'T EXPECT OR WANT GOBS OF GATTA TAR TEASE MEETINGS WE WANT UPPER LEVEL SUMMARIES, GREAT IF YOU HAVE THE DATA IN YOUR HANDS BUT THEY ARE UPPER LEVEL. SO WHAT ARE THE OUTCOMES OF A CRITICAL PATH TO INNOVATION MEETING, I THINK PRIMARILY THE IDENTIFICATION OF ISSUES FACING THE DEVELOPMENT OF A PROPOSED INNOVATION, OF COURSE THAT INNOVATION IS PRETTY BROADLY DEFINED, I THINK, SO IT WILL--IT CAN HAVE A GREAT IMPACT ON ON HOW YOU DESIGN A DRUG DEVELOPMENT PROGRAM. SO, WE MAY HELP YOU IDENTIFY AVENUES FOR BUILDING, THE COALITION WITHIN YOUR FIELD, CONSORTIA, PATIENT ADVOCACY GROUPS FOR EXAMPLE THAT WE MAY KNOW ABOUT, MAYBE YOU HAVEN'T HEARD, SOMEWHAT DOUBTFUL BUT IT CAN HAPPEN. INTEREST GROUPS AND OTHER COLLABORATORS, AND IF YOU CAME IN, LET'S SAY FOR A BIOMARKER, WE MIGHT BE ABLE TO HELP YOU IDENTIFY, DIFFERENT POTENTIAL USES OR A BETTER LET'S SAY, A MORE APPROPRIATE, MORE EASILY IMAGINABLE USE FOR THAT BIOMARKER IN A DRUG DEVELOPMENT PROGRAM. AND ONCE AGAIN AS I SAID IT'SAN SEX POSTURE OF FDA TO ETHE MERGING SCIENCE. SO AS I SAID, PROMISE SAID, THESE ARE THE RESOURCES AVAILABLE TO YOU TO LEARN MORE ABOUT T. WE DON'T HAVE A LOT OF TIME. I WILL BE AVAILABLE AFTERWARDS THERE, IS A GUIDANCE, AND THE INTERNET SITE THAT WE HAVE, YOU KNOW GOOGLE CRITICAL PATH INNOVATION MEETING, AND YOU'LL GET RIGHT HERE SO IT HAS A LINK TO THAT GUIDANCE, CAN YOU GO RIGHT THERE AND GET THE GUIDANCE, THE REQUEST FORM FOR SUCH A MEETING IS LINKED THERE. THERE'S A LINK TO A WEBINAR WHICH GIVES YOU MORE OF WHAT I I'M JUST TELLING YOU RIGHT NOW, AND THE E-MAIL ADDRESS WHERE OUR PROGRAM IS THERE, TELEPHONE, CONTACT, PUBLISHED THE--SHOWN YOU THE INTERNET ADDRESS HERE, BUT ALL YOU HAVE TO DO IS REALLY GLE IT. SO THESE ARE OUR CONTACTS, PROGRAM MANAGER IS ALICIA STEWART, MY NAME IS JAMES KISER DO I HAVE ONE MINUTE? SO, YEAH, I'M SORRY, I THINK I'M UNDER MOST PEOPLE'S TIME, ANYWAY, ANY RATE, SO SO THOUGHTS THAT OCCURRED ME TO CURDURE DURING A TRANSLATIONAL PIECE AND WHY DRUGS FAIL, AND THERE ARE MANY REASONS WHY THEY CAN FAIL IN A CLINICAL STUDY BUT THEY HAVE TO COME THROUGH WITH--THEY SHOULD COME THROUGH WITH A DESCENT TRANSLATIONAL PIECE BUT ONE THING HAVE TO KEEP IN MIND AD THIS IS A PLUG FOR ANOTHER CRITICAL STUDIES AND THIS IS GETTING RARE TRACTION IN OTHER DISEASE'S GROUPS. SO THE IDEA AND I JUST NOTICED WHEN I WAS UP THERE, ON THE DESK THERE, THAT THERE'S A RESOURCE FOR YOU CALLED REGISTRY OVERVIEW ASK RESOURCES I DON'T KNOW HOW MANY OF YOU SAW IT, BUT IT INCLAUDES IN PASSING MENTION OF THE VALUE OF THESE NATURAL HISTORY STUDIES AND I DRAW DISTINCTION BETWEEN A NATURAL HISTORY STUDY, SO A REGISTRY IS A PLACE WHERE INFORMATION AND DATA ARE COLLECTED BUT A REGISTRY CAN BE A SOURCE FOR NATURAL HISTORY STUDY AND THE BASIC IDEA BEHIND A NATURAL HISTORY STUDY IS TO UNDERSTAND YOUR DISEASE BECAUSE IT'S TO UNDERSTAND THE END POINT OF WHERE YOU'RE GOING IN YOUR DRUG DEVELOPMENT PROGRAM. MANY RARE DISEASES HAVE--A SCATTER SHOT OF PHENOTYPES. ONE DRUG MAY EFFECT A GIVEN MANIFESTATION OF THAT PHENOTYPE. BUT IF HAVE YOU 20 PATIENTS AND TWO OF WHICH HAVE THAT PHENOTYPE, THE DRUG CAN FAIL IN THAT STUDY. SO, WHAT YOU HAVE TO DO IN A NATURAL HISTORY, WHAT YOU DO IN A NATURAL HISTORY STUDY IS COLLECT AS MUCH INFORMATION AS YOU CAN ABOUT AS MANY PATIENTs AS YOU CAN AND UNDERSTAND THE DISEASE SO I WILL--I GUESS THERE'S MORE TO SAY ABOUT THAT BUT I WILL COME INTO YOUR ATTENTION THE NEW GUIDANCE CALLED THE RARE DISEASES, YOU CAN GOOGLE IT BY SAYING RARE DISEASE GUIDANCE FDA BUT IT'S COMMON ISSUES IN DRUG DEVELOPMENT. WE GO THROUGH THIS IN DRUG DETAIL AS WELL AS GOING THROUGH AS IT SAYS THE COMMON ISSUES IN DRUG DEVELOPMENT. THERE'S ISSUES OF HAPPENING YOUR DISEASE, THERE ARE ALSO SECTIONS IN IT ON CHEMISTRY MANUFACTURING AND CONTROLS CLINICAL END POINTS, BIOMARKERS SO I'LL CONCLUDE WITH THAT. I WILL BE AVAILABLE FOR SOMETIME AFTER THE SESSION HERE TODAY. AND AS CAN YOU SEE, MY CONTACT INFORMATION IS THERE, THANK YOU. >> [ APPLAUSE ] >> [INDISCERNIBLE] >> HI, THANK YOU, I HAVE THE DISADVANTAGE OF NOT ONLY BEING THE LAST SPEAKER OF THE LAST PANEL RIGHT BEFORE LUNCH BUT, YOU KNOW I FIND MYSELF IN THIS POSITION TO MAYBE KIND OF REACT TO THE COMMENTS THAT PEOPLE HAVE SAID ABOUT INDUSTRY. IN THE SENSE THAT JUST AS THE GROUPS HERE ARE EVOLVING THEIR MODELS OF WORKING WITH INDUSTRY, SO IS PFIZER AND I CAN ONLY SPEAK ON BEHALF OF PFIZER AND THE RARE DISEASE GROUP WITHIN PFIZER AND TO JUST TO GIVE A LITTLE CONTEXT ABOUT THAT, IN 2010 PFIZER LAUNCHED A DEDICATED RARE DISEASE RESEARCH UNIT WITH VERY SPECIFIC PRIORITIES. WE HAVE MAPPED OUR STRATEGY AGAINST RARE NEUROMUSCULAR, RARE HEMEATOLOGY AND RARE PULL MONITORROLOGY. MANY OF YOU MAY OR MAY NOT KNOW THAT PFIZER ACTUALLY HAS A LONG HISTORICAL PRESENCE IN RARE DISEASES, PRIMARILY HEMEATOLOGY, BUT IN 2010 WE SAID HOW CAN WE REALLY PAY MORE ATTENTION TO EVOLVING OUR MODEL AND ONE OF THE PILLARS OF OUR COMPANY, AND WITH THAT, THERE'S THE RECOGNITION THAT WE NEED TO THINK ABOUT THE DRUG PROCESS VERY DIFFERENTLY, THAN WE'VE HAD TO DO FOR HYPERTENSION, ASTHMA, INDICATIONS LIKE THAT. IN THAT THERE IS A MUCH CLOSER RELATIONSHIP BETWEEN THE BROAD COMMUNITY OF STAKEHOLDER WHICH IS IS YOUR ORGANIZATION, GOVERNMENT ENTITIES, ACADEMIC COLLEAGUES AS WELL AS INDUSTRY PARTNERS. SO I THINK WITH NOT ONLY DEFINING OUR PAST STRATEGIC PRIORITIES WE THOUGHT ABOUT HOW TO BUILD A MODEL TO ENGAGE AND ONE OF THE INNOVATIONS WE'VE STARTED AND WE'RE ONE OF THE ONLY COMPANIES THAT DOES THIS HAVE A--BITS INTERNAL PATIENT ADVOCACY FUNCTION EMBED IN THE RESEARCH UNIT TO WORK SPECIFICALLY WITH THE CREDIBLE EXPERTS THAT ARE IN THE PATIENT ADVOCACY GROUPS, SUCH AS YOURSELF, AND I'M SO IMPRESSED WITH THE BEST PRACTICE EXAMPLES THAT HAVE BEEN SHARED BECAUSE THESE ARE EXACTLY THE KIND OF MODELS THAT NEED TO BE BUILT AND CONTINUE TO BE EXECUTE UPON IN ORDER FOR ALL OF US TO MARCH A SHARED ADMISSION WHICH IS TO MORE EFFECTIVELY, EFFICIENTLY BRING QUALITY MEDICINE TO THE PATIENTS COMMUNIES AND YOU KNOW WE'VE HAD THE LUXURY OF WORKING WITH SEVERAL OF THE GROUPS THAT ARE REPRESENTED TODAY IN THE GROUP SO I DON'T ACTUALLY NEED TO GO THROUGH A LOT OF TIME BECAUSE I THINK YOU KNOW IN THE WORKSHOPS TODAY, SOME OF THOSE EXAMPLES WILL COME OUT. AND CERTAINLY AVAILABLE TO ANSWER ANY QUESTIONS THAT THAT EMERGE AS RIRESULT OF THIS PANEL. --AS A RESULT OF THIS PANEL. BUT JUST TO GIVE SOME EXAMPLES OF HOW WE ARE DOING THINGS DIFFERENTLY AND MAYBE A LITTLE OFF-TOPIC SINCE THIS PANEL IS REALLY EFFECTIVELY PARTNERING WITH INDUSTRY AND CLINICAL TRIALS, I THINK WE'RE MOVING TO A MODEL WHERE THERE'S TOO LATE. IF WE HAVEN'T ENGAGE INDEED OUR BASIC SCIENCE THEN, YOU KNOW THAT'S--THEN WE'RE NOT DOING OUR JOBS BECAUSE THE IDEA IS TO NOT ONLY TRANSLATE RELATIONSHIPS ACROSS DRUG DEVELOPMENT CONTINUUM BUT TO WORK WITH PATIENT ADVOCACY GROUPS AND SOME OF THE EXAMPLES I WANT TO HIGHLIGHT, WE'RE WORKING CLOSELY AND THE FREDERICK SPACE TO UNDERSTAND WHAT IS THE FOUNDATIONAL SCIENCE THAT IS THERE BECAUSE FOR US, IT'S ALL ABOUT DERISKING A DRUG DEVELOPMENT PROGRAM AND IF THE BASIC SCIENCE AS WELL, THE MOUSE MODELS ARE THERE, THE TARGETS ARE WELL KNOWN, HAVE YOU YOUR NETWORKS OF CLINICIAN RESEARCHERS, EXCELLENT THAT WE CAN TAP INTO, I CAN'T SPEAK HIGHLY ENOUGH ABOUT RON AND HIS ORGANIZATION AND HOW WELL THEY BUILT THAT FOR US. AND WORKING CLOSELY WITH SEVERAL OF THE MUSCULAR DYSTROPHY ADVOCACY GROUPS AND THEY SAT WITH US TO HELP US DESIGN OUR PHASE TWO CLINETAL TRIAL. SO GETTING TO THEM AT THE POINT OF RECRUITMENT IS TOO LATE AND THEY'RE INSTRUMENTAL IN SAYING WHAT ARE THE CHANGING PARADIGMS FOR ASSESSMENTS IN THERE SPACE. WHERE ARE THE TRIAL SITES THAT AREN'T NECESSARILY COMPETING FOR PATIENTS AND YOU MIGHT THINK ABOUT THE FACT THAT THEY HAVE CAPABLE, THEY'RE CAPABLE OF EXECUTINGOT STUDY DESIGN AS WELL AS AVAILABLE, SO JUST UNBELIEVABLY HELPFUL. SO THOSE ARE SOME EXAMPLES OF PATIENT ADVOCACY GROUPS WHETHER IT'S CLINICAL DESIGN SPACE OR CLINICAL APPROVED PROGRAM. [ APPLAUSE ] >> I'M AN EMPLOYEE OF PFIZER SO YES I GET PAID. >> WE'RE ALL STAFF. >> YES. >> I CAN SAY THAT FOR THE--PEOPLE WHO WORK WITH US ON THE NIH SIDE IN OUR NEUROTEXT PROGRAM, THEY'RE NOTES PAID WHEN THEY'RE ORIGINALLY HELPING US WITH PROTOCOLS BUT ALL OF OUR DSMB MEMBERS AND COMMITTEE MEMBERS THEY ARE PAID, IT'S NOT MUCH, IT'S THE GOVERNMENT, BUT THEY'RE PAID AS MUCH AS EVERYONE ELSE. >> CAN I JUST ADD, YOU KNOW OVER THE LAST TWO DAYS, YOU KNOW, THE IDEA, I THINK WE ALL AGREE ON THE VALUE THAT THAT PATIENT ADVOCACY ASSOCIATIONS PLAY IN THE DRUG DEVELOPMENT PROCESS, AND IF YOU AREN'T AWARE OR HAVEN'T SEEN, I KNOW THERE ARE MANY OF YOU WHO ARE ENGAGE INDEED BUILDING THE MODEL, THE CLINICAL TRIALS TRANSFORM PFATION INITIATIVE HAS PUT FORWARD A WONDERFUL MODEL FOR ALL THE OPPORTUNITIES TO ENGAGE WITH DRUG DEVELOPERS FROM A VERY EARLY SCIENCE THROUGH PRECLINICAL, THROUGH CLINICAL AND COMMERCIAL. SO IF THAT CAN BE MADE AVAILABLE, IT'S FANTAST AND I CAN RON MAY BE ABLE TO SPEAK TO THAT A BIT FURTHER. >> DEAN. >> DEAN WITH THE MLD FOUNDATION, WE'RE HERE AS THE NONPROFIT ORGANIZATIONS WITH OTHERS AND I JUST WANT TO KIND OF TAKE THE ROLE THAT RON DID YESTERDAY AND REMIND THE ORGANIZATIONS THAT WE ARE NOW--THIS IS THE CHANGING DYNAMIC, I SHOULD SAY BY THE WAY CATHERINE, I LOVE MY FORMA PARTNERS, I HATE THE 50 STORY BUILDING WITH THE COMPLIANCE OFFICERS, BUT THE REST OF THEM I LOVE AND THE UNDERLYING TONE HERE IS TO BUILD THOSE RELATIONSHIPS. AND THE REASON IT'S IMPORTANT IS BECAUSE WE NEAR CHANGING TIMES, BUT THE SUBMITTAL SCIENCE IS CHANGING WE TALK ABOUT DATA SCIENCE CHANGING, THE ROLES THAT ADVOCACY GROUPS HAVE, THE RELATIONSHIPS THAT ADVOCACY GROUPS AND THE CONNECTIONS WE HAVE WITH THE FDA AND NOT JUST US APPROACHES THEM, BUT THEM APPROACHING US, I MEAN THROUGHOUT, THE ROLES ARE CHANGING AND WE'RE ALL TRYING TO GET OUR ARMS AROUND THIS. FOR THOSE OF YOU THAT AREN'T AS BIG OR SOPHISTICATED OR HAVE THESE 2000 OR $2 MILLION BUDGETS, THOSE KINDS OF THINGS, I JUST ENCOURAGE TO YOU TAKE THOSE STEPS. WE TALK ABOUT THOSE PRECLINICAL THAT OVERLAYS HERE, WE WERE REALLY CONCERNED THAT WITH OUR REALLY, REALLY SMALL RARE DISEASE, WE'RE DOING NATURAL HISTORY STUDIES TO UNDERSTAND THE DISEASE AND WE STILL HAVE THAT MANY FAMILIES TO INVEST IN THE STUDIES AND PHARMA ONE WAS DOING THIS, AND ACADEMIA WAS DOING THIS AND SO ON AND THE FAMILIES WERE GETTING BURNED OUT IN THE STUDIES AND THERE WEREN'T EH OF THEM TO PARTICIPATE. AND WE HOSTED A MEETING AND BROUGHT TOGETHER THOSE PLAYERS AND CALLED WHAT WE HAD AN OPEN NIEHS, AND WE SAID NO MORE. WE SAID WE ARE TELLING FAMILIES NOT TO PARTICIPATE IN NATURAL HISTORY STUDIES, NOW THAT'S NOT A SUSTAINABLE STATEMENT BUT IN THE SHORT-TERM WE STOPPED ENROLLMENT OF NATURAL HISTORY STUDIES WHICH IS SHOULD GO WE CAN DO EFFECTIVELY TO BRING THOSE PARTIES TO THE TABLE. THEY ALL NODDED THEIR HEADS PRIVATELY AND SAID, WE WOULD LOVE TO SHARE THAT FREE CLINICAL DATA, TAKE ADVANTAGE OF THE OTHER FOLKS AND LIKE TO ADD TO THE POOL BUT IT CAME TO EXECUTION, THEY WERE STRUGGLING BECAUSE OF HISTORY AND STRUCTURES AND EVERYBODY'S GOT TO CONTROL THEIR OWN DATA SO THEY CAN CONTROL THEIR OWN DESTINY, BUT WE JUST--YOU KNOW A SMALL LITTLE ORGANIZATION WE STOP THAT WHOLE THING AND WE SAID WAIT A MINUTE. YOUR BEST WISHES ARE FINE BUT LET'S EXECUTE ON THAT. SO EVEN BABY STEPS, STEPPING UP TO THE PLATE, I WANT TO ENCOURAGE THAT YOU WHATEVER YOU THINK YOU CAN DO, YOU NEED NEED TO ASK PERMISSION, YOU DON'T NEED TO BE A PARTY AT A TILE. YOU UP HERE @ TABLE. SO ALL OF THESE THINGS YOOTS IMPORTANT THAT YOU DON'T JUST HAVE A ROLE BUT YOU HAVE A SEAT AT THE TABLE AND YOU'LL FIGURE OUT WHAT THAT LOOKS LIKE BUT THAT'S MORE AN EDITORIAL COMMENT THAN ANYTHING, BUT THANKS. >> LAST COMMENT AND THEN WE WILL GO TO LUNCH. >> I WONDER IF I COULD ASK DR. FERNANDEZ, I'M SURE AS A CONSEQUENCE OF A VERY IMPRESSIVE HISTORY THE PARKINSON'S STUDY GROUP HAS HAD IN RUNNING CLINICAL TRIALS HAS DEVELOPED A METASENSE OF THINGS THAT ARE READY FOR PRIME TIME AND THAT HAVE A CHANCE OF WORKING. IF A SPONSOR SHOWS UP AND HAS--LET'S ASSUME THEY HAVE THE MONEY AND THEY HAVE SOMETHING FOR PRIME TIME, REGULAR BODIES AND WELL TOLERATED, IS THERE AN ADDITIONAL FILTERING STAFF OF SAYING HOLD ON A SECOND, LIKE I REALLY DON'T THINK, YOU KNOW THIS IS READY YET, OR I DON'T THINK I THINK THIS IS A CHANCE OF WORKING IN THIS WAY AND ACTUALLY ASKING FOR ADDITIONAL NONCLINICAL DATA BEFORE YOU MOVE FORWARD. N. >> YES AND NO. THE REALITY IS THAT INVEST GATORS, THEY WOULD TAKE ANY DISTANCE, WHETHER IT'S ALMOST READY FOR PRIME TIME OR QUITE READY OR PAST PEAK EMPLOY ANYTHING THAT MAKES PARKINSON'S PATIENTS LIVES BETTER WE'LL TAKE. AND SO, THE BAR FOR, YOU KNOW AGREEING PARTNERING WITH SOMEONE WHETHER IT BE MICHAEL J. FOX FOUNDATION, THE NIH, THAT IS THE HIGHEST BAR BECAUSE--BUT INDUSTRY, WE ARE A PRODUCT WE THINK IS PROMISING, IS HONESTLY NOT THE HIGHEST. OF COURSE AS LONG AS IT'S SAVE, THERE'S REASON TO DO IT, THAT'S WHY WE DO THE CLINICAL TRIALS. IF I KNEW THE ANSWER IT WOULDN'T BE RESEARCH, RIGHT? SO, HAVING SAID THAT, WE ADVISE THEM, THERE'S THE PLANNING AND CONCEPTUAL PHASE, WE'RE PRETTY BLUNT ABOUT TELLING WHOEVER HAS THE INVESTIGATOR DEVICE OR DRUG BYOU KNOW WHY THIS IS VERY PROMISING WHETHER IT'S AN UNMET NEED OR NOT. BUT HAVING SAID THAT, IT'S STILL KIND EVER HAVE A CONFLICT BECAUSE I'M THE CO-CHAIR I WANT BUSINESS FOR MY CONSTITUENTS AND WE HAVE MOUTHS TO FEED AND SO, I'M ALSO VERY EAG TORE DO THIS AND SO, WE HAVE VERY AUTONOMOUS SCIENTIFIC ADVISORY BOARD, THE SAB, THEY'RE THE ONLY COMMITTEE THAT'S PAID FOR THE EFFORTS THAT THEY DO. THE REST OF US IS VOLUNTEER. BUDGET COMMITTEE TO MAKE SURE THAT IT IS FAIR PER SUBJECT FEE FOR EVERYONE. WE HAVE CREDENTIALLY COMMITTEE TO MAKE SURE NO ONE HAS A CONFLICT OF INTEREST, EVERYONE'S PREPARED, IT'S ALL VOLUNTEER, BUT THE SCIENTIFIC ADVISORY BOARD, ARE THE ONES THAT ARE ACTUALLY PAID JUST SOME AMOUNT PER GRANT PROPOSAL THAT THEY REVIEW. SO THEY CAN BE AS HONEST AND BLUNT AS POSSIBLE. SO ALL WE CAN DO IS GIVE THIS TO THE--THEY ACTUALLY ADVISE BOTH, THE EXHIBITINGATIVE COMMITTEE AND THE STEERING COMMITSEE OF THAT STUDY, DON'T DO THE STUDY, WHICH I'VE ACTUALLY NEVER SEEN, BUT THEY'VE--I'VE SEEN THEM AS FAR AS IF IT'S FAR AWAY, IF YOU CAN DO THIS, THIS, AND THAT, THEN WE THINK IT'S WORTH IT AND THEN WE ALSO GIVE THE SAME COPY TO THE INVESTIGATOR, TO THE SPONSOR. AND THE SPONSOR HAS A RIGHT TO BELIEVE IN IT OR NOT, AND THEY DON'T BELIEVE IT, THEY GO SOMEWHERE ELSE AND JUST DO IT THEMSELVES AND IF THEY WANT TO WORK WITH US, THEN THEY'LL FOLLOW THE STEPS THAT ARE PROPOSED BY THE SCIENTIFIC ADVISORY BOARD BECAUSE--AND THEN, ULTIMATELY THE EXECUTIVE COMMITTEE PUTS A STAMP ON IT THAT'S GOOD TO GO, SO WHEN IT'S A LARGER CENTER OF 250 INVESTIGATORS AND COORDINATORS ONE OF THE THINGS AS YOUR ORGANIZATION GROWS IT STARTED WITH 10 SITES AND NOW WE HAVE 132, OVER A SPAN OF 28 YEARS. YOU HAVE UNFORTUNATELY LAYERS OF COMMITTEES AND DOING THAT AND ALL WE CAN DO IS HAVE THESE CHECKS AND BALANCES THAT MAKE SURE IT WOULD BE THE RIGHT THING. >> I APPRECIATE YOUR HONESTY. I MEAN I THINK IT'S IMPORTANT TO HEAR THAT, I MEAN THERE'S CERTAINLY NO PREDICTING THE OUTCOME AS YOU SAY, THAT'S WHY CURE DOG THE TRIAL. THERE ARE SOME THINGS THOUGH, WITH A BIT OF SMARTS AND EXPERIENCE YOU CAN SAY THIS HAS NO CHANCE OF WORKING. AND SO I THINK EVERYBODY SHOULD SORT OF REALLY BE THINKING ABOUT THE RIGOR AND ROBUSTNESS OF THEIR FINDING AS A APPROACH THE CLINICAL TRIAL NETWORK, BECAUSE IF YOU CAN DO IT THE NETWORK WILL ACCEPT IT AND DO IT AND POTENTIALLY TIE UP A BUNCH OF PATIENTS THAT YOU MIGHT HAVE THOUGHT TWICE ABOUT DOING D OF TIME. APPRECIATE IT. >> AND WITH THAT WE'RE ALL GOING TO BREAK FOR LUNCH. WE INVITE TO YOU COME TALK WITH US IF YOU WISH TO DISCUSS THIS FURTHER IN ROOM A, CAN YOU SEE THE OTHER BREAK OUT GROUPS THERE SO CAN YOU TALK ABOUT BASIC TRANSLATIONAL AND THE STRATEGIC PLAN. >> THANK YOU. GO TO LUNCH. >> WHICH IS ACTUALLY ONE OF OUR--IN MY VIEW AS 11 OF OUR MOST POPULAR PROGRAMS, IT'S BEEN IN PLACE FOR MANY YEARS AND WHEREVER WE GO INVESTIGATOR'S ARE--SO,OT TRANSLATIONAL SIDE AND LEFT-HAND SIDE OF THE SPECTRUM WE HAVE--WE USED TO HAVE A PROGRAM CALLED TR21 WHICH ARE NOW SUN SETTED AND WE HAVE TWO ASSAY DEVELOPMENT AND IN VIVO AND EXVIVO, THOSE ARE TWO PARALLEL EPR'S THAT ARE PUBLISHED LATE LAST YEAR, WE'VE HAD TWO RECEIPT DATES ALREADY AND AS PART OF FIRST RECEIPT DATE, WE RECEIVED ABOUT 50 APPLICATIONS WE ARE TAKING THIS TO UPON THE COUNCIL AND AND SO SHE ACTUALLY OVERSEES THE THE BIOLOGICS THERAPEUTIC WHICH IS IS UNDER THE CREATE AND I'M SURE HE WILL TELL US MORE THAN THAT, WE HAVE NOW A VERY FOCUSED DEVICE THAT'S BEEN FUNDED THROUGH AN SBIR ROOT AND ALSO A GRANT ROOT, I DON'T KNOW HOW MUCH EMPHASIZE WE NEED TO PUT ON DEVICES BUT THAT'S AN AREA WHERE WE FEED INTO THE BRAIN INITIATIVE THAT FUNDS VARIOUS TOPICS THERE. DOWN FROM THAT IS WHAT THEY'VE BEEN DOING OVER THE YEARS WHICH IS THE SBIR, SCTR PROGRAMS AND THIS IS A CONGRESSALLY MANDATED PROGRAM WHICH I'LL BE FAMILIAR WITH AND WE FUND VARIOUS TRANSLATIONAL TOPICS HERE. MOST OF THE FUNDING GOES TO SMALL COMPANIES THAT ARE INTERESTED IN DRUG DISCOVERY AND DEVELOPMENT, BLUEPRINT THERAPEUTIC SYSTEM A PROGRAM WHICH STARTED ABOUT BLUEPRINT INITIATIVE, THAT INVOLVES 15 INSTITUTES THAT CAME TOGETHER AND PUT ABOUT $50 MILLION TOGETHER TO FUND VARIOUS TOPICS, AND SMALL MOLECULE TRANSLATION THAT WAS UNDER PRIVY OF ALL 15 INSTITUTES SO WE HAVE AMONG PROJECTS STARTED WE HAVE PROJECTS FOR ALL INDICATIONS, HEARING LOSS, ALZHEIMERS DISEASE, COGNITION, AND MANY OTHERS. SO FAR WE HAVE FUNDED 17 PROJECTS AND THEY IN THE PROGRAM, MYSELF AND CHUCK ARE PROGRAM LEADS FOR THE BLUEPRINT AND THEN WE HAVE THE COUNT ACT PROGRAM WHICH IS ALSO A MANDATED PROGRAM WHICH FUNDS VARIOUS SMALL MOLECULE INITIATIVES FOR CHEMICAL THREATS AND UNFORTUNATELY THE PROGRAM DIRECTOR IS NOT HERE TODAY BUT THAT'S AN INTERESTING TOPIC THAT MANY INVESTIGATORS ARE INTERESTED IN BECAUSE THEN THEY DON'T HAVE TO GO TO SBIR AND GET THE FUNDING. SO WITH THAT I'LL STOP AND PASS THIS TO SUSAN. >> AGAIN I'M SUSAN DICKINSON, I'M WITH THE ASSOCIATION FOR FRONTAL TEMPERRAL DEGENERATION, AND I THINK AS I DESCRIBE THIS MORNING WHAT INTERESTED ME THE MOST ABOUT THIS SPACE IS ONE THE THINGS IS HOW WE DO GET THE DIFFERENT PLAYERS TO COLLABORATE THIS THE PRECLINICAL SPACE AND THAT'S SOMETHINGA WE'RE ON THE BLINK OF TRYING TO MAKE HAPPEN. SO, I'D BE INTERESTED IN HEARING ANY SPECIFIC EXAMPLES OF EXACTLY HOW YOU GET THE EGOES TO BE CHECKED AT THE DOOR, IF THAT'S YOUR PHRASEOLOGY. I THINK THAT'S-- >> SO TOPICS OF DISCUSSION AS WELL. >> SO JAMES MACARTHUR, CHIEF SCIENTIFIC OFFICER AT PSIDEON, SO WE'VE LOOKED AT THOUSANDS OF PROGRAMS, PROBABLY OVER MY CAREER BUT VERY SIMILAR THEMES IN TERMS OF LOOKING FOR ASPECTS OF THOSE PROGECS THAT MAKE THEM TRANSLATABLE, AND ONE THING WHICH I'M ENJOYING RIGHT NOW IS ESSENTIALLY BEING ABLE TO REACH OUT DIFFERENT GROUPS AND ACTUALLY HELP, EVEN WITH EARLY STAGE PROJECTS THAT AREN'T QUITE READY FOR OUR PROCESS TO BOTH PROVIDE ADVICE IN SOME CASES PROVIDE CAPITAL AND BRING PEOPLE TOGETHER AND SO TO YOUR LATTER POINT, WHERE WE'VE HAD GROUPS THAT ARE BRINGING DIFFERENT COMPONENTS TO THE PROJECT, IF WE CAN ARGUE ABOUT THE PERCENTAGES UNTIL WE'RE BLUE IN THE FACE, IF WE DON'T GET TOGETHER AND MOVE THIS FORWARD, WE THERE WILL BE NO MONEY COMING FORWARD, THERE WILL BE NO MONEY FROM THOSE PERCENTAGES AND LET'S NOT WORRY ABOUT THOSE DETAILS FOR THE SUCCESS BECAUSE IT WILL ALL WORK OUT IN THE END BECAUSE EVERYONE CAN CIRCLE THE WAGONS AROUND THEIR PARTICULAR PHILOSOPHY ABOUT WHAT THEIR RELATIVE VALUE IS TO A PROJECT AND YOU HAVE TO GET PEOPLE PASSED THAT TO REALIZE IF WE DON'T START COLLABORATING THAT THEIR IS NO PATH FORWARD. >> I'M WITH ASTRAZENECIA, WHERE WE ARE ACTUALLY WORKING WITH CHUCK AND OTHERS WHERE WE LICENSE THE ASSAY FROM THE AWARDLYS, THE THERAPEUTICS SMOKING CESSATION AND I THINK THIS IS A CLEAR EXAMPLE OF COLLABORATION WHERE THREE DIFFERENT PARTIES WHO ALL HAVE VESTED INTERESTS, WHO ALL HAVE DIFFERENT SKILL STETS OVERLAPPING, SOMETIMES NOT ARE ABLE TO COME TOGETHER, SOMETIMES THEY ARE EASY, THEY HAVE DIFFERENCES THAT IT HAS BEEN A GOOD, SIX OR EIGHT MONTHS NOW WHERE WE'VE WORKED TOGETHER WHERE IT IS PR HAS THE BASIC TARGET OF THE SCIENCE AND WE HAVE THE DEVELOPMENT OF EXPERTISE, BUT THE DRUG DEVELOPMENT AND EXPERTISE AND THE WHOLE NECKANISM FOR ENABLING THIS TO HAPPEN HAS REALLY BEEN A GREAT COLLABORATION, I'M NOT SURE ANY ONE PARTY ON ITS OWN COULD HAVE DONE AS GOOD A JOB AS THE THREE PARTIES TOGETHER ARE DOING. >> HI, I'M BREVIE HAS IN S, AND I ACTUALLY HAVE AN MBA, BUT THE INTEREST IS IN THE SMALL BUSINESS RESEARCH, AS WELL AS TRANSLATIONAL RESEARCH. HOWEVER WE HAVE NOT REALLY FUNDED MANY CLINICAL TRIALS SO TELL BE INTERESTING TO SEE HOW WE CAN TRANSLATE THINGS FROM THE BENCH INTO MORE OF A--YOU KNOW TRANSLATABLE FORUM AND I THINK IT'S HIGH LIE IMPORTANT TO REALLY PARTNER WITH A LOT OF INDUSTRY AND OTHER COLLABORATORS AND IT'S BEEN MENTIONED THIS MORNING BUT I THINK THAT'S HOW WE DO TWE FOCUS ON THE MECHANISTIC FOR ADVOCACY GROUPS AND PARENTS AND STAKEHOLDERS TO REALLY UNDERSTAND HOW TRANSLATION WORKS. >> HI, I'M JOHN KEEN, FROM THE SCREENING PROGRAM THAT AMIR REFERRED TO AND THIS PROGRAM HAS BEEN IN PLACE CONTINUOUSLY SINCE 1975, IT WAS SET UP AT THE TIME TO FILL AN UNMET NEED IN EPILEPSY WHICH IS THERE WERE VERY FEW TREATMENT OPTIONS AVAILABLE FOR PATIENTS WITH EPILEPSY. IT'S BEEN VERY SUCCESSFUL IN CONTRIBUTING TO ABOUT 10 DIFFERENT MARKETED DRUGS AND IT'S--ONE OF THE HALLMARKS HAS BEEN A PRESERVICE OFFERED BY THE NINDS, SO PEOPLE FROM ACADEMIA, OR FROM INDUSTRY CAN SUBMIT COMPOUNDS TO BE TESTED IN A BATTERY OF SCREENING ASSAYS. AND AND IN THE LAST FIVE YEARS OR SO THERE'S BEEN A SHIFT IN EMPHASIS OF THE PROGRAM BECAUSE NOW THERE ARE A LOT OF SYMPTOMATIC TREATMENTS FOR EPILEPSY THAT ARE AVAILABLE ON THE MARKET AND AND THE MEDES FOR EPILEPSY TO CURE THE DECEASES, DISORDERS PREVENT THE DEVELOPMENT OF EPILEPSY AS WELL AS ALTER ITS PROGRESS AND TREAT CO-MORBIDITIES AND OF COURSE WITH MOST DISEASES, THERE'S A FARM KORECYST ANT POPULATION OF PEOPLE WHO DON'T RESPOND WELL, SO IT'S A BIG CHALLENGE FOR THE PROGRAM AND AND THAT'S WHERE WE'RE GOING NI'M ALEX KLEIN, I'M THE VICE PRESIDENT OF SCIENTIFIC AFFAIRS FOR QPSP, MY BACKGROUND IS IN BIOLOGY, LEFT SCIENCE TWO YEARS AGO SO MY BRAIN AND STILL THINKING MOSTLY LIKE A SCIENTIST, YET AS A NONPROFIT PERSON, AND I'M HERE FOR, WELL, FIRST OFF MAKING NEW FRIENDS, NONPROFIT FRIENDS AND NEW POSITION QPC NEVER HAD A SCIENTIFIC DIRECTOR OR VICE PRESIDENT IN THIS POSITION AND ALSO, YOU KNOW BY JUMPING MY BACKGROUND IS PARKINSON'S DISEASE BUT NOW I'M WORKING ON THEL TELEOPEN MEETINGATHY AND GOING INTO THIS FIELD I REALIZE IT'S ALL COMING TOGETHER AND WE NEED TO COLLABORATE AND FOR THAT REASON, I WOULD LIKE TO INQUIRE AND FIND OUT WHERE WE SHOULD PUT OUR PREFERENCES AND TOGETHER IS WHERE WE CAN FIND THE SHARED INTEREST, THANK YOU. >> HI, I'M ANGELLA TAILOR AND I'M WITH THE LOUIS BODY PREVENTION ASSOCIATION, I'M A PATIENT ADVOCATE, LBDA HAS SPENT MOST OF OUR YEARS REALLY SERVING THE PATIENT AND CAREGIVER COMMUNITY RAISING PUBLIC AWARENESS, EDUCATING HEALTHCARE PROVIDERS AND WE ARE IN THE PROCESS OF DEVELOPING OUR OWN RESEARCH STRATEGY AND I'M HERE TO LEARN MORE ABOUT THE OPPORTUNITIES TO COLLABORATE WITH MEN THEM, WE ARE WORKING WITH THE MAYO CLINICOT DLD CONFERENCE WHICH TAKES PLACE THIS DIAGRAM SO I THINK THE FIELD IN IS IN A POSITION WHERE THERE'S A LOT OF MOMENTUM WHERE WE'RE HINDERED BY LACK OF BIOMARKERS DIAGNOSTIC CRITERIA AND FAMILIESITY AT THE PRIMARY CARE LEVER SO WE HAVE A LOT OF WORK TO DO SO IT'S A YOUNG FIELD AND--WE HAVE GOOD EXAMPLES OF THE OPPORTUNITIES AVAILABLE. HI, I'M REBECCA WITH THE TYPE FOUR FOUNDATION. WE ARE HERE BECAUSE OF COLLABORATIVE DISCUSSIONS THAT HAPPEN, SO ECHOING A LOT OF THE COMMENTS, THAT HAVE ALREADY BEEN MADE I THINK LIKE MANY OF THE DISEASES REPRESENTED HERE, ML-FOUR IS SORT OF AND MARKED AND BESET BY DIFFERENT SCIENTIFIC COMPLEXITY AND IT HAS DEPENDED ON THE DISCOVERY PHASE, BASIC SCIENCE PHASE ON A GREAT DEAL OF COLLABORATION, THAT'S BEEN TRUE OF THE KIND OF CONFERENCES THAT WE HAVE HELD WHERE THE SCIENTISTS WHO WE HAVE BROUGHT TOGETHER REALLY DON'T NATURALLY OTHERWISE MEET WITH EACH OTHER SO THERE HAS BEEN A REALLY FANTASTIC ENVIRONMENT OF COLLABORATION AND SHARING AT THOSE MEETINGS. WHERE THOSE MEETINGS ARE THE SINGULAR SPACE WHERE MANY OF THOSE INDIVIDUALS HAVE A CHANCE TO COME AND SHARE THAT KIND OF INFORMATION AND WE ARE REALLY EAGER TO CONTINUE AND FIND WAYS AND STRUCTURES AND MECHANISMS FOR CONTINUING THAT KIND OF COLLABORATIVE WORK AND TRANSLATIONAL ENVIRONMENTS THAT WE'RE SORT OF HEADING INTO. PARTICULARLY AS WE LOOK TO KIND OF WIDE AND THAT GROUP OF INVESTIGATORS BEYOND OUR SORT OF NATURALLY OCCURRING COMMUNITIES IF YOU WILL WHICH IS A BIG EMPHASIS AT THIS MOMENT. >> I'M MR. LAROSA, OUR ORGANIZATION IS 100% FOCUS ON FIBROMITOSIS SO IT'S A BENIGN CONDITION FOR TUMORS. WE HAVE A LOT OF OPPORTUNITIES ONGOING, AND THE CONSORTIUM WHICH HAS BEEN RUNS FROM 2008 AND TESTING EXTENSIVELY, WE HAVE ANIMAL MODELS, MODELS AND INFORMING A LOT OF CLINICAL TRIALS AND AND PROBABLY ASTRAZENECA, IS A PARTNER AND NOW WE'RE STARTING A REGISTRATION TRIAL FOR WHAT SEEMS TO WORK IN AN F-ONE. SO THIS IS AN EXCITING MOMENT. WE HAVE A REGISTRY, WE HAVE A CLINICAL TRIAL CONSORTIUM, WE'RE VERY LUCKY THAT MOST OF THEM ARE THERE AND WE CAN LEVERAGE MOST OF THEM. WHAT I'M INTERESTED IN, IS TODAY IS TO LEARN ABOUT OTHER FOUNDATION, OTHER ORGANIZATION, AND YOU KNOW HOW TO BRING THIS MODEL TO THE NEXT LEVEL, WE KNOW WE HAVE BEEN SUCCESSFUL BUT MOST OF THE SUCCESS IS COPY CAT FROM THE CANCER FIELD. AND OUR DISEASE IS REALLY SOMETHING DIFFERENT. I MEAN WE CANNOT PUT TREATMENTS, CANCER TREATMENTS IN OUR PATIENTS BECAUSE THEY NEED TO STAY CHRONICALLY FOR OUR LIFE. THIS IS ALT PATIENTS, A LOT COFF COMPLICATION BUT THEY CANNOT BEAR MOST OF THESE TREATMENTS SO WE NEED SOMETHING SPECIFIC AND WE ARE REALLY STRUGGLING WITH BASIC SCIENCE TO MAKE THIS HUGE SHIFT FROM CELL DEATH TYPE OF READ OUTS TO SOMETHING THAT IS MORE MEAN BEINGFUL FOR OUR DISEASE. AND WE HAVE A LARGE COMMUNITY OF 400 RESEARCHERS. BUT THE WAY OF THEIR MIND SET IS, REALLY, REALLY, I MEAN ANCHOR TO THIS CANCER APPROACH. SO IT'S A LEARNING OPPORTUNITY SO WE ARE TRYING TO BUILD A PLATFORM, BRING THE TOOLS. CHALLENGE THEM WITH NEW IDEAS, BUT THIS IS OUR MAIN STRUGGLE, I SAY AT THIS MOMENT IN TIME. - >> --MANAGE A LARGE NUMBER OF CLINICAL TRAINING FELLOWSHIPS FOR OUR MEMBER WHO IS ARE MUCH EARLIER IN THEIR CAREER, AND WE ARE REALLY TRYING TO FOSTER AS A PART OF--AS SORT OF A PREPART OF THAT PROGRAM WE'RE TRYING TO FOFTSER A LOVE AND AN INTEREST IN NEUROSCIENCE AND K-12 AND THEN AN UNDERGRADUATE POPULATIONS AND SO, WE COME HERE SO WE CAN FORM RELATIONSHIPS, WE CAN FIND OUT A LOT ABOUT AREAS WHO HAVE NEEDS BECAUSE WE'RE LOOKING FOR PROFESSIONALS THAT HAVE RESEARCH OPPORTUNITYS SO IT'S BEEN A PLEASURE TO EVERYONE IS NETWORK A BIT MORE. >> I'M DEBORAH, WITH THE CEREBRAL PALSY RESEARCH FOUNDATION AND IT'S EXCITING TO BE HERE TO MEET EVERYBODY AGAIN IN NETWORK AND TRYING REALLY TO PH MORE COLLABORATION, NOT JUST IN THE WORLD OF CEREBRAL PALSY BEYOND THAT AS WELL, OUR FOUNDATION HAS GONE THROUGH A HUGE SHIFT WITH NOW NO LONGER A FOUNDATION WHO JUST GIVES GRANTS, WE'RE REALLY LOOKING AT PROVIDING A PROJECT MANAGEMENT AND THE ADMINISTRATION CAPABILITIES FOR THE INSTITUTION TO BE ABLE TO PUSH THROUGH MARKETING AND PR OF ALL THEIR RESEARCH AS WELL. SO, YES IT'S INTERESTING TO HEAR WHAT EVERYBODY'S UP TO. >> I'M RONNIE AND I'M WITH THE CATASUL CORPORATION, WE ARE AN OLD NEW DISEASE OR A NEW OLD DISEASE. WE'VE JUST REALLY GOTTEN A LATE DIAGNOSE AND TELL US EXACTLY WHAT CAUSES THIS DISEASE AND I'M HERE TODAY TO BRAINSTORM AND PICK EVERYBODY'S MINDS TO FIND OUT WHERE ARE THOSE ASSOCIATIONS WITH THE YOUNG KIDS ON THE BLOCK, FIND OUT WHAT EVERYBODY ELSE IS DOING, TO FURTHER THEIR CAUSE, AND TO GET THE HELP THAT THEY NEED SO WHEN WE HEAR PEOPLE TALKING ABOUT WE HAVE A SMALL BUDGET ONLY IN THE MILLIONS, WE CHOKE BECAUSE OUR SMALL BUDGET IS ONLY IN THE HUNDREDS. AT THIS TIME. SO HERE HERE TO LEARN. HI, I'M ANN, CONFOUNDER AND PRESIDENT OF THE CATASUL ASSOCIATION, CATASIL IS A RARE DISEASE, A MONOGENIC DISEASE, IT'S AN ACRONYM FOR CEREBRAL AUTOSOMAL DOMINANT ARE--ADMINISTRATIVE TIERIOPATHY WITH SUBCORTICAL INFARCTS WITH INSEVERE MITRAL LA OPEN MEETINGATHY. IT HAS TO BE THE LONGEST NAME. >> MORE INITIALS THAN ANYBODY ELSE. >> OKAY. --AND ANYONE WHO WILL LISTEN TO US IT'S A LITTLE KNOWN DISEASE BUT IT'S MUCH MORE PREVALENT THAN PEOPLE HAVE BEEN--MUCH MORE PREVALENT THAN PREVIOUS THOUGHT, IT'S CURRENTLY MISDIAGNOSED MS, BUT AT LEAST HALFFUL HALF OF OUR PATIENTS IN OUR SUPPORT GROUP COME TO US AND SAY, I WAS PREVIOUSLY DIAGNOSED WITH MS, OR MY AUNT WAS AND YOU KNOW THEY FIND OUT THEY HAVE CATAZONE AND ONCE YOU HAVE A RELATIVE CAN CATASILLIN, YOU EXPERIENCE THE SYMPTOMS AND THEY'RE SIMILAR TO MS, THE NUMBNESS, THE--THEY START OUT USUALLY WITH HEADACHES WITH MIGRAINES, WITH AURA, THEY PROGRESS TO T. I. A.s AND STROKE LIKE EPISODES. SOME HAVE SEIZURES, SOME PEOPLE DON'T. SEIZURE SYSTEM MAYBE 20% OF OUR POPULATION BUT THE HALLMARK POINT IS WHEN THEY HAVE A FULL BLOWN STROKE, THESE ARE PATIENTS THAT ARE 20, 30, 40, 50, YEARS OLD, THERE'S A WIDE RANGE THERE, 2 YEAR-OLDS HAVING A STROKE SHOULD SEND UP A FLAG IF THERE'S A FAMILY HISTORY OF ANY NEUROLOGICAL DISEASE. WE STARTED OUR FOUNDATION IN 2012 SO WE'VE BEEN THROUGH--NETWORKING WITH PEOPLE, WE'VE BEEN COMING TO THE NIH FOR THE LAST FOUR YEARS. WE HAVE A RESEARCHER AT HARVARD WHO'S DOING RESEARCH ON CATASAL. HE AS A BIOMARKER AND HOPEFULLY HE HAS MICE THAT HE'S USING A COMPOUND ON THAT'S SHOWING PROMISE. SO I KNOW WE'RE STILL IN THE MICE THING SO WE HAVE A LONG WAY TO GO. WE'RE HERE JUST TO YOU KNOW BIND IT OR GET ADVICE FROM EVERYONE AND GET HELP. ONE OF OUR MAIN PROBLEM SYSTEM FINANCES, BECAUSE OUR FAMILY'S, WE DON'T HAVE ANY WEALTHY FAMILIES, WE DON'T HAVE ANY CELEBRITIES AND IT'S HARD TO GET OUR FAMILIES IN WITH FUNDRAISING, WE'RE LIMITED WITH THAT, TOO, SO WE NEED HELP, THANK YOU. >> I'M CHRIS AND I'M AT NIMDA, [INDISCERNIBLE]--ANOTHER PART OF MY LIFE AT NINDS, INVOLVE WIDE INTRAMURAL SIDE. WHEN YOU THINK ABOUT NIH, YOU THINK EXTRAMURAL BUT THERE'S ALSO INTRAMURAL SIDE AND OUR NEEDS ARE VERY SIMILAR, WE NEED PARTNERSHIPS, WE NEED ACCESS TO DATA AND BYEE REPOSITORIES WE NEED ACCESS SO IT'S VERY SIMILAR. SO TYPICALLY, THEY'RE INVASIVE AS A P. I. IT'S NOT WORKING. >> [INDISCERNIBLE]. >> --THEY FILE A PATENT AND THAT'S THE END OF THE STORY AND THEN IT'S KIND OF A PASSIVE WAY OF DOING TRANSLATIONAL RESEARCH. NOWADAYS THERE'S MORE OF A PROACTIVE APPROACH TO IT, WHERE WE TRY TO ESTABLISH CONTRACTS OR PARTNERSHIPS AND ADVANCE SOME OF THESE TECHNOLOGIES WHERE THE COMPANY MAY BECOME MORE INTERESTED IN IT. SO, AGAIN WE NEED HELP IN TERMS OF PARTNERSHIPS AND IDEAS AND WHAT WOULD BE EXTREMELY HELPFUL IS TO HAVE MORE OF A BROADER ACCESS TO IDEAS OF WHAT THE NEXT KEY EXPERIMENTS WOULD BE TO TAKE A TECHNOLOGY FROM THE BASIC, BASIC KIND OF SCENARIO TO MORE OF A TRANSLATIONAL APPROACH. >> HI, I'M HAO WONG, AND I OVERSEE BIOLOGICS AND WE HAVE THE LEGACY TRANSLATIONAL COOPERATIVE AGREEMENT, STILL ACTIVE PROJECT IN THAT. SO I'M VERY EXCITED TO BE HERE TODAY BECAUSE I THINK EITHER YOU'RE A PATIENT ADVOCACY GROUP, NONPROFIT GROUP, WE WANT TO UNDERSTAND YOUR NEED AND HOW WE CAN HELP AND WHETHER YOU ARE A SMALL BIOTECH OR PHARMACEUTICAL COMPANY, WE WANT TO ALSO LIKE LEARN HOW TO SHARE THE LESSONS LEARNED AND ALSO LIKE HOW WE PARTNER BETTER TO HELP THE FIELD TO MOVE FORWARD. SO ON MY PERSONAL SIDE, I WAS TRAINED AS A NEUROSCIENTIST FROM A PHARMACOLOGIST, AND I ACTUALLY WENT TO THE INDUSTRY, SO I WAS AT MERCK FOR ABOUT NINE YEARS AND I WAS AT TNJ FOR FIVE YEARS IN 98 ABOUT TWO YEARS AGO, SO I REALLY WANTED TO BE ABLE TO HELP IN THIS AREA AND MY AREA OF EXPERTISE, IF YOU SPEND FROM RESEARCH IN THE LAST EIGHT YEARS, ACTUALLY I DID THE CLINICAL RESEARCH. SO, AND--IT'S SIMILAR TO WHAT JIM WAS SAYING THAT IN TERMS OF, IN THE INTERACTIONS WITH THE INVESTIGATOR'S SO WE--WE ARE GRANT MECHANISM FOR THIS PROGRAM, BUT WE DON'T JUST, YOU W LET THE GRANT COME IN AND GO THROUGH THE PEER REVIEW. WE DO ENGAGE WITH THE INVESTIGATORS, YOU KNOW IN THE APPLICATION PROCESS, WE DISCUSS WITH THE INVESTIGATORS, ABOUT WHETHER THEY FIT THE SCOPE AND WHAT OTHER CRITICAL GAPS WE CAN HELP THEM TO BE MORE SUCCESSFUL, IN THE EARLY STAGE AND OF COURSE, AND OF TO REVIEW, THE FOUNDATION MADE, WE WORK WITH GRANTEES CONSISTED PROPERTY AGREEMENT AND WE HELP EITHER BY--YOU KNOW AS A TEAM WITH A PROGRAM DIRECTORS, ON THIS AREA. TO TRY TO HELP WITH THE BEST SITUATION FORWARD. S THE PROGRAM ITSELF JUST FOCUSING ON ANYTHING THAT'S NOT MOLECULE OR NOT DEVICES, BUT PEEP TIDE, PROTEINS, IN THERAPY, CELL THERAPY, NUCLEIE O TIDES AND EMERGING ENTITIES, ALSO FALL INTO THIS CATEGORY. THE STAGE OF THIS DEVELOPMENT IS ANYWHERE FROM DISCOVERY TRACT AND IT IS DEVELOPMENT TRACTS, SO DISCOVERY TRACTS STARTS WITH THE THERAPEUTIC LEAD WHERE YOU'RE STILL OPTIMIZING THAT, OR CHARACTERIZING YOUR LEAD AND THEN ONCE YOU AND I& D STUDYING AND ENABLE THE FIRST IN HUMAN CLINICAL TRIAL. WE CAN TALK MORE ABOUT THAT IF YOU HAVE QUESTIONS. >> OKAY, I'M CHUCK SIWIN, I'M SCIENTIFIC MANAGER OF THE ON THERAPEUTICS PROJECT, IT'S A SMALL MOLECULE PROJECT. AND IT'S TOTALLY FOCUSED ON TEAM WHO IS DOESN'T HAVE MUNICIPAL CHEMISTRY SUPPORT, MEANING AN EARLY STAGE PROJECT AND THAT HAVE SOME SORT OF VALIDATED SMALL MOLECULE AND WE PARTNER WITH EXPERTISE FROM CONSULTS AND SAFF TO MOVE THOSE PROGECS FORWARD SECOND GENERATION, THEY HAVE THE CHEMISTRY AND THEY CAN DO THE CHEMIST AND BIOLOGY TEAMS THAT NEED THE DEVELOPMENT SUPPORT, AND AGAIN THIS TEAM WILL PROVIDE THE DRUG DISCOVERY AND DEVELOPMENT EXPERTISE IN TERMS OF CONTRACT SUPPORT EXPERTISE IN STAFF AND EXPERTISE IN BEING ABLE TO PARTNER WITH OTHER FOCUS OUTSIDE OF NIH, THROUGH OUR NETWORKS TO HELP THE PROCESS ALONG. SO THE TRUE VALUES THAT I SEE WITH ALL THE NONPROFITS HERE IS YOU GUYS ARE ON THE FRONT LINES WITH PEOPLE WITH BIOLOGY SIDE AND A LOT OF THOSE FOLKS ARE LOOKING FOR WAYS TO GO FORWARD SO I CERTAINLY ENCOURAGE YOU GUYS TO MAKE THE NETWORK CONNECKS WITH THE STAFF HERE AT NINDS, BECAUSE WE CAN POINT THEM IN THE DIRECTION OF SOME OF THEIR MISSING PIECES AND HOW THEY POTENTIALLY FILL THOSE GAPS, GET THE PRELIMINARY DATA THEY NEED AND HOPEFULLY MOVE THE PROJECTS INTO IGNITE OR IN THE CAN OR CREATE THE BIOLOGICS OR CREATE DEVICES FOR DEVICES. PERSONAL BACKGROUND FOR ME IS I TELL I'VE BEEN AT NIH FOR ABOUT FUR YEARS PRIOR TO THAT AND I WORK FOR BARRING AND GOLD HEIM PHARMACEUTICAL FOR 18 YEARS SO I HAVE A PHARMA BACKGROUND AND I AM VERY INTERESTED IN MAKING THE BLEND BETWEEN THE DIFFERENT CONSTITUENCIES VERY SMOOTH AND THE ONE TRUISM OF THIS IS YOU CAN'T HAVE TRANSLATIONAL RESEARCH WITHOUT GOOD BASIC RESEARCH, WE CAN'T HAVE GOOD CLINICAL RESEARCH WITHOUT GOOD TRANSLATIONAL RESEARCH SO IT IS A CONTINUE ALL ASPECT VS TO BE FOSTERED. >> THANKS, CHUCK. >> WE'RE WEARING THEM OUT SO I'M JOHN PORTER CEO OF FAIR PROJECT MUSCULAR DYSTROPHY, THOSE THAT ARE FAMILIAR WITH THE NIH, A LOT OF THE INTRAMURAL PROGRAM IS LOCATED NINDS LOCATED NOT TO FORE FRANCIS COLLINS HERE AND THAT'S THE JOHN PORTER BUILDING, IT'S NOT ME, I'M NOT THE FORMER CONGRESSMAN FROM ILLINOIS, BUT I--WHEN I WAS AT NIH, I FIGURED I COULD HELP PEOPLE REMEMBER MY NAME, SO, SO PPMD, IS A PATIENT ADVOCACY GROUP FOCUSED EXCLUSIVELY ON DUCHENNE AND MUSCULAR TRYST KICKOFF COY AND AND OUR FOUNDER FAT FURLONG STARTED THE ORCHNIGHATION ABOUT 21 YEARS AGO NOW, SHE LOST TWO KIDS TO DUCHENNE. LTS OF PARENTS HAVE CHILDREN THAT THEY LOSE TO THESE DISEASES AND THEY FORM THESE ORGANIZATIONS AND I THINK ANYBODY THAT KNOWS PAT, KNOWS THAT SHE GOES A HUNDRED MILES AN HOUR, RIGHT? SO WE DO JUST ABOUT ANYTHING THAT HAS TO DO WITH DUCHENNE'S WE DON'T CROSS ANYTHING OFF THE LIST, WE KEEP ADDING, WE HAVE A REGISTRY THAT AS A PCORI, GRANT, WE HAVE A CONTRACT WITH ACADEMICS TO DO REPLICATION STUDIES, WE RELEPICATE CLINICAL STUDIES, WE HAVE GUIDANCE WITH FDA, ADVOCACY GROUP, DEVELOP, THE DISEASE, THE SPONSOR CANS LOOK ONLINE AND KNOW HOW THE FDA USE THERAPY DEVELOPMENT IN DUCHENNE, SO WE DO A LOT OF DIFFERENT THINGS BUT I GUESS THE ONE THING I SHOULD SAY IN THIS, VENUE IS, MY FORMER LIFE WAS 20 YEARS IN ACADEMICS AND 21 YEARS IN ACADEMICS, SOMETHING LIKE THAT. THE LAST CASE WAS NORTHWEST EXPERN 11 YEARS AGO, I CAME TO NINDS AND I WAS PROGRAM DIRECTOR FOR SPINAL MUSCULAR ATROPEY FOR 10 YEARS AND I GOT ENGAGED WITH YOU GUYS, REALLY. I ALMOST AS SOON AS I CAME HERE, SHARON HESTERLY FROM MDA, PAT FURLONG, I WAS POUNCED UPON BY PEOPLE IN THE PATIENT ADVOCACY GROUP. WHICH IS EXACTLY WHAT YOU SHOULD DO, I KNOW I'VE SEEDS A FEW TIMES TODAY, THEY ARE GREAT PEOPLE, AT NINDS, YOU HAVE TO FIND YOUR PERSON AND PALS AND ENGAGE THAT PERSON SO I GOT INTO THE MODEL OF PATIENT ADVOCACY GROUPS WHEN IT WAS TIME TO PUSH THE RESET BUTTON GAIN, I WAS LOOKING FOR A JOB IN PATIENT ADVOCACY SO THESE PRACTICALS TO THESE PRACTICALS, I ENGAGE FROM THE NINDS, AS A PROGRAM DIRECTOR BUT MY CURRENT ORGANIZATION ENGAGED IN THESE FROM THE OTHER SIDE, SO I WAS LIKE BEATING THEM IN THE MIDDLE. ONE OF THE SUCCESS STORY SYSTEM THAT THE CURRENT PROJECT MUSCULAR DYSTROPHY, ASSAY DEVELOPMENT AND HIGH THROUGHOUT PUT SCREENING EVALUATOR, THEY SPENT TWO-$3 MILLION ON WITH THE BIOCHECK. AND GOT ONE FOR THE THERAPY DEVELOPMENT. WE HAVE TO LEVERAGE, I KNOW I SAID THAT EARLIER BUT I DON'T THINK THIS ORGANIZATION HAS THE MONEY ON DO ALL THIS. SOME REALLY COOL SUCCESS STORIES ARE WHERE SHOULD I START. SO SPINAL MUSCULAR ATROPHY, IT'S A RESEARCHER IN NATIONWIDE CHILDREN'S HOSPITAL IN COLUMBUS OHIO THAT GOT A $275,000 R21. HE WANTED TO TRY GENE THERAPY IN THE SMA, DELTA SEVEN MOUSE, THESE MOUSE DIE ABOUT 14-15 DAYS AFTER USING THE GENE THERAPY, HE WAS SACRIFICING THEM AT 150 DAYS, SO THAT'S KIND OF--ANYBODY THAT KNOWS ABOUT INCREASED SURVIVAL AND NEUROLOGICAL DISEASES, YOU USUALLY DON'T GET THAT KIND OF INCREASED SURVIVAL. I MEAN THEY WOULD HAVE LIVED A FULL LIFE SPAN, I THINK. SO THAT GOT THEM GREAT DATA, WE GOT $700,000 FROM FAMILIES OF SMA, AND THE INVESTIGATOR OF THE ADVOCACY GROUP TO COME INTO THE UR-ONE PROGRAM AND GET MAYBE 6 MILLION-DOLLAR UL-ONE AND FOR THAT, IN THEIR CLINICAL TRIALS. NOW PUSHING THAT ALONG, NOW THAT KIND OF LEVERAGE SYSTEM WHAT YOU WANT TO USE THESE PROGRAMS FOR AND I THINK YOU NEED TO TALK WITH THESE GUYS. I MEAN PERHAPS THE BEST EXAMPLE IS ANOTHER ONE THAT STARTED OUT WITH LITTLE $275,000 GRANT FOR THE DYSTROPHY, ULTIMATELY AFTER UL-ONE ENDED UP BEING A PARTNERSHIP WITH BIOGEN WHERE THEY'RE PUTTING IT UP TO $200 MILLION, AND THINKING THROUGH PHASE THREE, AND PRECEDING MOUSE LINES SO THESE ARE RARE DISEASES, EACH OF THESE ARE RARE DISEASES AND IT START WIDE A SMALL INVESTMENT EITHER FROM ADVOCACY OR THROUGH AN NINDS GRANT OR COULD MAKE THINGS HAPPEN. I WOULD AGAIN BEFORE I PASS THIS OFF, I WOULD CONTINUE THAT PARTNERING IS THE ONLY WAY TO GET THIS DONE. NO ONE HAS THE RESOURCE TO MAKE THIS HAPPEN. SO LOOK TO THIS GROUP, BECAUSE I'VE BEEN ON BOTH SIDES OF FENCE NOW WITH THESE GUYS AND I THINK, TRY TO UNDERSTAND THESE PROGRAMS AND TAKE ADVANTAGE OF THEM. HOW'S THAT FOR APPLAUD. SO I COME FROM A DIFFERENT SPACE NOW WHERE MY NAME IS MARTIN, I WORK FOR [INDISCERNIBLE] WHICH IS A LARGE GOVERNMENT CONTRACTOR FIRM, BEFORE THIS I WAS [INDISCERNIBLE]. SO I BASICALLY DEVELOP ALL THE INFRASTRUCTURE TO START FUNDING THE APPLICATIONS AND PRIOR TO THAT, I WAS WITH THE [INDISCERNIBLE] FOUNDATION WHERE WE ACTIVELY HELP THE FDA, FOR [INDISCERNIBLE] PANCREAS WE DEVELOP, AND BEEN DEVELOPING. THE REASON I'M HERE IS BECAUSE HIGHWAY PATROLFULLY ON OCTOBER FIRST, WHEN WE TALK ABOUT PARTNERSHIP, WE ARE GOING TO START WORKING WITH NIS, AND PUBLIC PRIVATE PARTNERSHIP, THAT WE TALK ABOUT FUNDING BUT AS YOU KNOW, BACK IN THE 90S NIH WAS FUND BEING 30% OF THE APPLICATIONS, NOW THEY'RE FUNDING SOMEWHERE IN THE 10-15% OR EVEN SO WORRY OF THE PROJECT SO THIS WILL DO IS ALL THOSE REALLY GOOD APPLICATIONS THAT ARE NOT BEING FUNDED BY NIH, NOW, AND WE'RE TALKING ABOUT THE ENTIRE INSTITUTE, THEY WILL START WORKING WITH BIOMEDICAL FOUNDATIONS LIKE YOURS IN PHARMA TO SEE IF WE CAN FUND THIS APPLICATION SO WE CAN MOVE VIA THE RESEARCH PROGRAM. SO THERE ARE SOME FOUNDATIONS THAT ARE ALREADY GOING TO BE PART OF IT AND WILL START THE PILE UP IN OCTOBER. AND PROBABLY LAUNCH IT COMPLETELY IN NOVEMBER AND HOPEFULLY THERE WILL BE MANY MORE FOUNDATIONS THAT WILL JOIN THIS PROGRAM AS WELL IN PHARMA SO CAN YOU LEVERAGE THE MONEY YOU CAN FUND THROUGH WHAT PHARMA CAN BRING SO IT'S AN EXCITING THAT HOPEFULLY WE CAN START ANNOUNCING MORE BROADLY OVER THE NEXT FEW WEEKS. >> I KNOW IT LOOK A LITTLE WHILE TO GET INTRODUCED BUT I THINK IT'S CRITICAL SO THAT WE KNOW THE CONTEXT OF ANY QUESTIONING. SO WITH THE SLIDE HERE ARE THERE ANY QUESTIONS ABOUT FUNDING MECHANISMS FOR TRANSLATIONAL RESEARCH, THIS IS PROBABLY THE BEST TIME TO KICK THE TIRES AND UNDERSTAND WHAT IS THERE, THAT'S WORKING WELL AND WHAT'S NOT WORKING IF YOU WANT TO KNOW ANY ADDITIONAL DETAIL, WE CAN SECOND WORLD WAR SOME OF THE QUESTIONS YOU MAY HAVE. >> YOUR PROGRAMS ARE RFAs OR ARE YOU JUST THERE AND YOU TAKE MEETINGS, PEOPLE THINK THEY'RE READY TO GET TO YOU, WHAT'S THE PROCESS FOR EVEN STARTING TO BE CONSIDERED FOR ONE OF THESE PROGRAMS? >> SO WE DO ISSUE THE OPPORTUNITY ANNOUNCEMENTS AND THIS NIH, AS WELL AS OUR WEB SITE, IN THE OFFICE TRANSLATIONAL RESEARCH AND WE HAVE EACH PROGRAM HAS IT'S OWN WEB SITE AS WELL, WITH THE SPECFICS ACTUALLY ALSO SO YOU'RE WELCOME TO SEND THE LINK OR SEND THAT TO THE P. I. >> THAT'S ALL--P. A. R. AND SOMETIMES THEY ARE, YOUR SYSTEM AO P. A. R., THIS TIME, RIGHT? THIS, THERE'S THREE PANELS AND MOST OF WHAT THEY REVIEW IS THIS PROGRAM. THEY REVIEW OTHER STUFF BUT IT'S MAINLY THIS PROGRAM, SO THERE'S INDUSTRY FOLKS. SO WITHIN OFFICE OF TRANSLATIONAL RESEARCH, WE ARE A BROADER DISEASE AGNOSTIC AND WHAT WE DO IS PARTNER UP WITH A PROGRAM DIRECTOR WHO OVERSTEYS THE DISEASE SPACE TO TO FIELD ANY QUESTIONS WE MAY HAVE AND BE BY INVESTIGATOR WAS INTERESTED IN OUR PROGRAM. SO THE EASIEST WAY TO REALLY DO THIS IS TO JUST GET AHOLD OF EITHER ONE OF THEM, EITHER ON A DISEASE SIDE OR IF YOU KNOW THAT YOU HAVE A PEPTIDE THERAPEUTIC THAT YOU WANT TO PURSUE, THEN SEND AN E-MAIL TO HOW AND WHAT HAPPENS BEYOND THAT IS HOW WILL TEAM UP, IF YOU HAVEN'T TALKED TO SOMEBODY WHO IS THE DISEASE SPECIALIST WITHIN THE OFFICE, SHE WILL FIND THE RIGHT PERSON FOR EXAMPLE IF THIS IS AN ALSO HYMER'S PROJECT, ROD WOULD BE THE PROGRAM DIRECTOR, AND THEN, THEY WOULD WORK TOGETHER TO SET UP SOME TIME TO TALK TO THE INVESTIGATOR AND EXPLAIN ALL THE INS AND OUTS ABOUT THE PROGRAM ANNOUNCEMENT AND THE DISCUSSION ALWAYS STARTS WITH MAYBE A ONE PAGE SUMMARY, THAT HAS THE PROPOSALS, SPECIAL AIMS IF THERE'S ANYTHING AT THAT STAGE, THERE'S REALLY A 30 MINUTE, PHONE CALL THAT OUTLINES THESE AND THERE ARE SOME OF THESE ON THE WEB SITE, SOME OF THESE CAN JUST GET A LINK TO AND YOU CAN QUICKLY FIGURE OUT SOME OF THE BASICS, WHEN IS THE NEXT RECEIPT DATE, HOW MANY PAGES CAN A PROJECT BE, WHERE IS THE REVIEWED. AND SOME OF THE BASICS BEYOND THAT, IT'S PROBABLY BEST TO JUST TALK TO PDs OR ANYBODY WITHIN NINDS, TO GET THAT SPECIAL INFORMATION. WE ARE PAID TO TALK TO PEOPLE SO THAT'S SORT OF SOMETHING THAT WE DO. WE HAVE IT ON OUR CALENDARS AND IF YOU LOOK AT ANY OF OUR CALENDARS, IT'S ESSENTIALLY FULL BUT WE ACCOMMODATE TIME TO MAKE SURE WE TALK TO AS MANY PEOPLE AS POSSIBLE SO EVERYBODY'S FAMILIAR WITH IT, BUT IT'S REALLY SURPRISING HOW LITTLE PEOPLE KNOW ABOUT SOME OF THESE PROJECTS, FOR EXAMPLE, I'VE HEARD THIS MANY TIMES WHERE PEOPLE SAY, WELL I HAVE THE PROJECT WHERE I WANT TO DEVELOP AN ASSAY TO SCREEN SOME COMPOUNDS. WE HAVE THAT. IF YOU DON'T MIND WAITING FOR AN APPLICATIONS PLILGPLICATION TO GO THROUGH THE SYSTEM AND IT IS NORMALLY ABOUT A NINE MONTH PROCESS BUT BY THE TIME AN APPLICATION COMES IN UNTIL THE FUNDS ARE AVAILABLE TO DO THE WORK AND IF YOU DON'T MIND WEIGHT TAG LONG, YOU WILL GET NONDILUTED FUNDING WHICH IS ACTUALLY SOMETHING CRITICAL FOR A LOT OF INVESTIGATORS TO BE ABLE TO HAVE INTELLECTUAL PROPERTY TO THEMSELVES TO HAVE ALL THE FREEDOM TO ESSENTIALLY GO OUT AND WORK THOUGH ARE A CONSIDERATION ASK QUICK LOOK OF ANY OF OUR PDs AND A QUICK CONVERSATION WILL GET YOU QUITE FAR AND READY HOPEFULLY FOR PUTTING IN THE APPLICATION FOR ONE OF THESE PROGRAMS. >> WE HAVE THREE CASES RIGHT NOW WE'RE WORKING WITH ACADEMICS WHO HAVE SCREENS OR CONCEPTS WHERE WE'VE HAD THE SORT OF CONVERSATION OF SHOULD YOU GO AND APPLY FOR A GRANT AND IT'S OFTEN THE CASE WE'RE IMPATIENT AND SO WE'RE LIKE JUST GIVE YOU A HUNDRED THOUSAND DOLLARS, WE'LL JUST DO THAT, WE'LL FIGURE IT ALL OUT ON THE BACK END IN TERMS OF HOW WE'RE MOVING FORWARD IN YOU'RE SUCCESSFUL CAN THEY APPLY FOR GRANTS AND SO IF WE'VE ALREADY FUNDED THE WORK, THE WORK THAT'S INITIATED, GIVEN THERE'S A NINE MONTH PERIOD OF TIME, WE'RE NOT LOOKING FOR THE MONEY, BUT WHERE THE MONEY GOES BACK INTO THEM TO FUND THE NEXT STAGE. BY THE TIME THE MONEY WAS AVAILABLE, IF THAT FIRST STAGE WORK HA BEEN SUCK SESSIONFUL, THEY WOULD THEN USE THAT MONEY FOR THE NEXT STAGE OF WORK. THE OTHER QUESTION, IS WE HAD THE PROGRAMS FOR THE PRECLINICAL STAGE AND WE'RE ALWAYS LOOKING FOR PROGRAMS TO GO TO MEETINGS TO MEET PEOPLE TO TRY AND FIND THOSE PROGRAMS, WHAT'S THE BEST WAY FOR A COMPANY LIKE OURSELVES TO INTERACT, ON THE BACK END OF THESE SORT OF PROCESSES, WHERE YOU'VE GOT ACTIVITIES TO GO THROUGH THE PACES AND MOVE THEM FORWARD WHERE YOU CAN'T RECOMMEND ANYONE, LIKE YOU SHOULD TALK TO THESE PEOPLE BUT IS THERE A MECHANISM BY WHICH WE COULD DO SPEED DATING ESSENTIALLY AND MEET THOSE PEOPLE ON THE BACK END OF YOUR SCREENING PROCESS. >> SO HOW DID YOU FIND OUT ABOUT--- >> I ONE WAS DIFFERENT. I DIDN'T FIND OUT THROUGH THE NIH BUT I CAN SAY IF YOU ANY INTO THE NIH WEB SITE NINDS, WEB SITE THAT'S A LISTING, I THINK IT'S MAYBE THE NEXT [INDISCERNIBLE] OF ALL THE GRANT AWARDEES WITH THE TOPIC OF THE TITLE OF GETTING SEARCHES, ET CETERA. THERE'S PROSECUTION, THERE IS A PROCESS THEY ARE OBSESS WIDE THAT SO YOU GET TO THE PACK END AND THERE'S A CONVERSATION THAT YOU HAD AND I HAD ON THE PROGRAM, FROM NCATS, SORT OF OPENING THIS MORNING NCATS OVER AT NOVARTISAND I WENT OVER AND AH THAT'S INTERESTING, LET'S TALK ABOUT IT. >> I'VE FOUND WE HAD CONVERSATIONS WITH SEVERAL OF THE GRANT AWARDEES AND CASES. SOMETIMES THESE CONVERSATIONS TAKE SO LONG THAT EVEN WHILE THERE'S A PROCESS OF PROSECUTING A GRANT PROGRAM, IT STARTS THE DISCUSSION, YOU ARE ABLE TO DO TWO THINGS, ONE GET IN ON THE GRANT LEVEL BUT ALSO ALSO INCLUDE ENSEL THE RESEARCH THAT ARE BEING DONE SO CAN YOU PUT INTO YOUR PERSPECTIVE, SO YOU'RE NOT GETTING A PACKAGE WHERE YOU'RE SAYING, BUT FOR ME TO ACCEPT IT OVER MY TO ACCEPT TI NEED THIS, THIS AND THIS, SO AGAIN NOT TO KEEP GOING BACK TO THE ONE ACTIVE PLANT BUT THAT'S WHAT WE'RE DOING, WITH THE VPN AWARD BECAUSE WE ALL HAVE DIFFERENT STANDARDS, NUANCES, EATS IT IS BUT GETTING IN EARLY, SO WHILE WE'RE NOT INVESTING FUNDING FOR THE PROGRAM, BECAUSE THE VPN IS COVERING THE ACTIVITIES, ONE PIECE WE FOUND FOR EXAMPLE, IS TRANSLATIONAL ACTIVITY WERE NOT REALLY COVERED AS PART OF THE BCL, SO THE WAY A BIG PHARMA WOULD LOOK AT TRANSLATION, WHETHER YOU LOOK AT EFFICACY BIOMARKER OR TRANSLATION BIOMARKERS, WE'RE ABLE GET IN GROUND UP AND RUN THE KIND OF STUDY WE WANT TO RUN EARLY ON TO BUILD THAT WHICH YOU CANNOT DO TO WAIT AND AFTER THE PROGRAM IS DONE SO THERE'S A LOT OF PERCENTAGES, TO GET IN EARLY. [INDISCERNIBLE]. >> SO THERE'S A COUPLE DIFFERENT WAYS TO GET AHOLD OF US WE HAVE ON OUR WEB SITE, A GROUP CALLED REPORTER WHERE YOU CAN ACTUALLY SEARCH BY THE DISEASE FIELD YOU'RE INTERESTED IN AND SO ON AND SO FORTH AND EVERYTHING WITHIN AN ABSTRACT OF A GRANT IS ACTUALLY PUBLICLY AVAILABLE. SO CAN YOU SCAN THINGS AND WITHIN OUR WEB SITE, WE ACTUALLY HAVE LISTED ALL THE ACTIVE GRANTS AND EVERYTHING THAT'S REPORTED IS ALSO AVAILABLE THERE SO CAN YOU QUICKLY GO THROUGH THIS. GO TO YOUR FIRST QUESTION, I WISH THERE WERE MORE OF THAT HAPPENING. I WISH THERE WERE MORE SITUATIONS WHERE DISCIPLINES COME TOGETHER, INVESTIGATOR CAN PARTNER UP WITH A BUSINESS GROUP THAT SAYS, THESE ARE THE MISSING PIECES AND HERE'S A GRANT MECHANISM THAT COULD ACTUALLY SOLVE YOUR SOLUTIONS AND IN FACT, THE PIs THAT DO QUITE WELL, ARE THE ONES THAT HAVE PARTNERSHIPS IN PLACE AND HAVE LETTERS OF COMMITMENT THAT SAYS, I AM WORKING WITH COMPANY X AND THE COMPANY X HAS OFFERED TO PROVIDE ME UNDER A MATURE TRANSFER AGREEMENT, ALL THE MATERIAL I NEED TO DO MY EXPERIMENT. THAT REALLY GOES PRETTY FAR, VERSES A FISHING EXPEDITION LIKE WE'RE TALKING ABOUT YESTERDAY, WHICH DOESN'T GO WELL FOR THE INVESTIGATOR. SO HAVING A CONCISE SET OF EXPERIMENTS THAT ARE DEEMED CRITICAL, HAVING ALL THE MATERIAL, AND HAVING SOME KIND OF FUNDING THAT ESSENTIALLY COLLABORATES AND BRINGS THE DOLLARS AND THE KNOW HOW ARE REALLY CRITICAL FOR SUCCESSFUL APPLICATION. >> --WERE FOUNDED BY THE COMPANY AND WE'RE RECEIVING NIH FUNDING AND KNOW SOME OF THIS, U-ONE OR COOPERATIVE AGREEMENT MECHANISMS CAN BE MOUSE ON, OR THE FURTHER FOUNDING WAS DEPENDING ON THE ACHIEVEMENT OF THESE MILESTONES SO THAT IS POSSIBLE. >> SO THE STRONGEST ONES HIAS A PROGRAM DIRECTOR WERE PARTNERSHIPS WHERE IT'S AN ACADEM BEING PICOUPLED WITH A COMPANY, SO THAT ONE THAT TURNED INTO THE BIG COLLABORATION WITH BIOGEN AND MYOTONIC DYSTROPHY, WHEN THAT FIRST CAME IN, IT WAS A PARTNERSHIP BETWEEN THE ACADEM AND I CAN ROUGH ATOM JESTER WHO REALLY KNEW THE DISEASE WITH JINSA, AND INTERESTINGLY ENOUGH A GREAT EXAMPLE THAT CAUSED THIS TO DO WELL IN REVIEW IS THAT [INDISCERNIBLE] INSISTED ON INDEPENDENTLY REPLICATING THE DATA SO THEY HAD THE ACADEMIC AND THE MICE, THE OTHER PARTNER WAS THE UNFORT HATELY NAMED BIOTECH ISIS, OKAY? I'M SURPRISED THEY HAVEN'T CHANGED THEIR NAME YET. >> [INDISCERNIBLE]. >> RIGHT. RIGHT. TELL THAT TO A BUNCH OF PEOPLE, RIGHT, RIGHT. SO THE ACADEMIC PEOPLE HAD DEVELOPED THE DAT AGENZYME STARTED THERE, AND WITH THAT KIND OF EXPERTISE, THAT APPLICATION DID TERRIFIC IN REVIEW, OKAY. IT DOES, AND THEN THE APPROACH THAT YOU DO, I WOULD THINK WOULD BE GREAT TO PARTNER WITH THIS BECAUSE FROM WHAT I KNOW ABOUT YOUR PROACH THRU CHRISTINA, YOU AND I HAVE TALKED ONCE OR TWICE IS THAT JUST ASKING THE KILLER QUESTION, I MEAN PUTTING--HAVING IT SPELLED OUT THAT WAY, HERE IS WHATY WOO KNOW ABOUT THIS CANDIDATE THERAPEUTIC IN HERE OR THE REALLY KILLER QUESTIONS AND WE'RE PUTTING THEM IN WITH THE MILESTONES AND COMING INTO THIS PROGRAM. I COULD SEE IT SUCCEEDING THE FIRST PASS. WON OF THE THINGS WE THINGS-- >> ONE OF THE THINGS WE PAY ATTENTION TO IS THE TARGET PROFILE AND MANY OF OUR INVESTIGATORS THROUGH THE PROFILE ARE NOT FAMILIAR WITH IT UNLESS THEY STARTED TO ROLL UP THEIR SLEEVES AND WORK WITH YOU OR WITH SOMEBODY THAT CAN SEE THE END GOAL AND CAN RECOGNIZE THE END GOAL AND APPRECIATE THE CHALLENGES TO GET TO THAT STATE AND IF THAT'S REFLECTED IF THAT PATH IS REFLECT INDEED THE PROPOSAL, IT MAKES SENSE AND I'VE HEARD THIS FROM REVIEWERS WHERE THEY SAY, I KEPT WANTING TO READ MORE BECAUSE IT'S ACTUALLY SUCH A WELL WRITTEN COMPELLING SORT OF A PATH WHEN THE REVIEWERS LOOK AT THAT PROPOSAL THEY CAN LOOK AT THE SHOES AND THEY CAN SAY I CAN RELATE TO THAT AND THAT MAKES A PROPOSAL STAND OUT. >> I WAS ALSO GOING TO ADDRESS THE SECOND QUESTION ABOUT SPEED DATES--[LAUGHTER] >> YOU KNOW WE DO SOMETIMES PARTICIPATE IN BIOAND [INDISCERNIBLE] CONFERENCES WHERE THE U.S. IS INVITED TO PARTICIPATE. >> ANOTHER THING WE'VE DONE THOUT OUTREACH AND PART OF THAT OUTREACH IS WALK AROUND WITH THAT PACKAGE OF INFORMATION THAT WE HAVE FOR ALL OF OUR GRANTEES, THAT'S PUBLIC AND SAY, WELL, WE HAD THESE PROGRAMS IN THIS DISEASE AREAS ARE YOU INTEREST IN THIS AND THEN IF YOU ARE INTERESTED WE CAN HOOK UP UP, AND THEN WE CAN SIGN FURTHER ANTS OBVIOUSLY BUT THE OTHER THING HASN'T BEEN MENTIONED IS THERE'S SMALL BUSINESS TRACTS THAT WILL CREATE WHICH ALLOWS THEM TO COME INTO THE PROGRAM AND SOME ADVANTAGES AND SMALL BUSINESS TRACT IN TERMS OF MAKING THEM SET ASIDE BUT OVERALL IT GIVES PEOPLE OPTIONS OF SMALL BUSINESS TO COME IN AND LATER STAGE REALLY LEVERAGE WHAT WE HAVE FOR ANY OF THE STRUCTURES, I THINK IT'S IMPORTANT TO KNOW [INDISCERNIBLE]. >> SO I'M GETTING A SIGN THAL IS THE END OFFER SESSION HERE SO I ENCOURAGE EVERYONE TO EXCHANGE INFORMATION AND CARTS SO WE CAN KEEN TRACK OF EACH OTHER AND IF YOU EVER NEED TO TALK TO ANY OF US, PLEASE LET US KNOW, WE ARE HERE. GOOD AFTERNOON, WE JUST HAD A SESSION WHERE WE INTRODUCED SOME OF THE HIGHLIGHTS OF OUR PROGRAMS, WITHIN OFFICE OF TRANSLATIONAL RESEARCH AND WE ESSENTIALLY WENT AROUND AND HAD EVERYBODY INTRODUCE THEMSELVES AND TELL US THEIR INTEREST LEVELS IN OUR PROGRAMS AND WHAT THEY DO, AND WE JUST HAD AN OPEN DISCUSSION ABOUT SOME TOPICS OF INTEREST THAT WE'RE GOING TO DO. IF THAT'S OKAY, WE'LL JUST CONTINUE WITH THAT. SO, MY NAME IS AMIRAKA, I'M ONE OF THE PROGRAM DIRECTOR WITHIN THE OFFICE OF TRANSLATION RESEARCH, AT NIH FOR ABOUT THREE YEARS. AND AS A WAY OF INTRODUCING ALL OF US, THERE'S A FEW PROGRAM DIRECTORS HERE THAT WE'LL SPEAK ABOUT THEIR PROGRAMS BUT I WANT TO HIGHLIGHT SOME OF THE THINGS WE DO WITHIN OUR OFFICE. SO, ACCORDING TO THAT SLIDE THERE WE COVER LATE DISCOVERY ON THE LEFT-HAND SIDE TO THE EARLY TRIALS ON THE RIGHT HAND SIDE WHICH IS DEPICTED IN GREEN. SO WE HAVE SEVERAL PROGRAMS TAYLOR MADE FOR RESOURCES AND TOPICS WITHIN TRANSLATIONAL RESEARCH, SUCH AS SMALL POLARIZED KIEWLS, LARGE MOLECULES AND OTHER PROGRAMS SUCH AS THE [INDISCERNIBLE]. SO FROM THE TOP OF THE ASP PROGRAM, WHICH WE REFER TO SO JOHN KING IS THE PROGRAM DIRECTOR NEAR THE ASP AND HE'LL TELL US MORE ABOUT THIS PROGRAM AND SUBSEQUENT TO WHAT WE USED TO HAVE WHICH IS THE TR--A PROGRAM KNOWN AS THE TR21 PROGRAM WHICH WAS SENSITIVE LAST YEAR, WE HAVE A MENU OF SEVERAL PROGRAMMINGS WITHIN WHAT WE CALL IGNITE WHICH ARE INNAIVATION GRANTS, NURTURE TRANSLATIONAL EFFORTS AND WE HAVE TWO P A Rs AVAILABLE THAT ARE TAKING APPLICATIONS ONE FOR ASSAY DEVELOPMENT AND ONE FOR SCREENING EFFORTS AND THOSE ARE BOTH COUPLED WITHIN THE SAME P A R. THE SECOND P A R WHICH IS ALSO KNOWN AS P A R 15071 IS FOR DEVELOPING PROOF OF CONCEPT STUDIES IN VIVO OR EXVIVO THROUGH SOME KIND OF ANIMAL MODEL THAT SOMEONE WOULD BE INTERESTED IN. SO FAR, THE IGNITE GRANTS ARE ALL THREE YEAR GRANTS UP TO ABOUT $750,000. INVESTIGATORS HAVE ACCESS TO $250,000 AS PART OF THE R21 PHASE AND THEY REMAIN AND CAN BE ACCESS OF R33, SO THESE ARE TWO STAGES OF THE OF THE GRANT. WE HAVE THE BIOPROGRAM, LINDA OVERHERE, IS ONE OF THE PROGRAM MANAGERS TO CREATE BIOAND SHE WILL TELL US ON THE STAGES AND VARIOUS PROJECTS WITH THE PLAN. AND WITHIN THE UMBRELLA WE HAVE DVICES AND WITHIN OUR PROGRAMS WE HAVE TWO FUNDING OPPORTUNITIES FOR SBAR PATH AND ALSO TO A REGULAR GRANT PATH. THE SBIR AND SCTR PROGRAMS WHICH YOU'RE THE MOST FAMILIAR WITH ARE THE CONGRESSALLY MANDATED PROGRAMS AND A SET ASIDE MONEY TO FUND A NUMBER OF PROJECTS EVERY YEAR FOR THESE TOPICS. THE BLUEPRINT NEAR THE THERAPEUTICS NETWORK IS SOMETHING THAT I WORK WITHIN AND PACIFICAL LINK ON THAT THERE, SO P A SCAL JOINED US AND WHAT WE DO WITH THE THERAPEUTICS NETWORK AND WE PROVIDE GRANT FUNDING AS WELL AS RESOURCES TO ADVANCE SMALL MOLECULE PROJECTS. WE HAVE SEVERAL CONTRACTS IN PLACE, WE PROVIDE STATE OF THE ARM CHEMISTRY RESOURCES, WE PROVIDE THE TALKS RESOURCES I& D STUDIES AND MANUFACTURE AND ALSO CLINICAL TRIALS. SO THERE WE HAVE THE PHILOSOPHY THERE AS TO REALLY SURROUND PIs BY FIELD EXPERTS, AND ALSO CONSULTANTS THAT HAVE ACTUALLY BEEN VETERANS IN THE INDUSTRY TO REALLY GIVE THEM ALL THE RESOURCES THEY NEED TO BE SUCCESSFUL AND WE ALSO HAVE TE COUNTER PROGRAM, WHICH IS THE COUNTERMEASURES FOR CHEMICAL THREAT AND THESE ARE SMALL MOLE PROJECTS THAT DAVID WHO WAS THE PROGRAM DIRECTOR FOR THE PROJECT WAS HERE TODAY. ONE OF THE GOALS I HAVE IS SORTED CENTERED AROUND ALL OF THIS IS I WOULD LIKE TO GET FEEDBACK ON SOME OF THESE PROGRAMS. SO AS WE DEVELOP THESE PROGRAMS, WE WANT TO KNOW IF IT'S RESONATING POO PEOPLE. IF THERE ARE FUNDING OPPORTUNITIES THAT PEOPLE CAN TAKE ADVANTAGE OF AND WHETHER THESE ARE THINGS THAT ACTUALLY MACK A LOT OF SENSE AND AS PART OF THIS, WE'RE HERE TO TELL YOU ALL ABOUT THESE PROGRAMS, SO IF THERE ARE SPECIFIC QUESTIONS, LINDA AND I AND PASCAL WILL TALK ABOUT THESE THINGS. WITH THAT WE WILL GO AROUND. >> HI SUSAN DICK KNOW SON, YOU ALL HEARD ME THIS MORNING, EXECUTIVE DIRECTOR OF THE ASSOCIATION FOR FRONTAL TEMPERRAL DEGENERATION, AND WE'RE A FAIRLY YOUNG, SMALL, NONPROFIT AND WE'RE ON THE CUSP OF MEETING SOME OF THESE WONDERFUL RESOURCES SO IT'S TERRIFIC TO LEARN THAT THEY'RE HERE, LIKEWISE I THINK OUR INVESTIGATORS ARE BEGINNING TO EXPLORE SOME OF THESE THINGS AS WELL, WE DID USE THIS BEFORE, THE RARE DISEASE CLINICAL RESEARCH NETWORK JUST LAST OCTOBER. SO I THINK THAT THE LAST SESSION, IT WAS--IT WAS VERY HELP. WE JUST WENT AROUND THE ROOM TO HEAR WHAT EVERYBODY IS, AND WHAT YOUR INTEREST IS IN THE TRANSLATIONAL SPACE AND ESPECIALLY CAN HIT SOME OF THE NINDS TRANSLATIONAL OFFICE PEOPLE AND HEAR MORE ABOUT THESE PROGRAMS IN PARTICULAR. >> I'M JOHN KING HEAD OF THE SCREENING PROGRAM THAT AMIR TALKED ABOUT TODAY. SO IT'S A UNIQUE PROGRAM WITH THE NINDS, AND CONTRACTOR PROGRAM AND IT'S BEEN IN PLACE WHO WAS SET UP ON THAT NEED AND TREATMENT OF EPILEPSY AT THE TIME AND THOSE WERE TREATMENT MARGINS SO THE PROGRAM'S BEEN SUCCESUL, USES A BATTERY OF ANTISEIZURE ASSAYS TO COMPOUNDS THAT ARE SUBMITTED BY ACADEMIC PARTICIPANTS, INDUSTRIES, OTHER GOVERNMENT AGENCIES, AND THAT'S--IT'S FREE OF CHARGE AND HAS CONTRIBUTED TO BRINGS ABOUT 10 DIFFERENT MEDICATIONS TO MARKET OVER THE YEARS. IT'S--WE'VE HAD OVER 600--JUST IN THE PROGRAM, SCREENED OVER 31,000 COMPOUNDS SO IT'S BEEN A VERY, VERY PRODUCTIVE PROGRAM AND IN RECENT YEARS WE'RE TRYING TO ADDRESS THE UNMET NEEDS IN THE AREA OF EPILEPSY AND ARE SHIFTING AWAY FROM THE SEQUENCE DISCOVERY TO FARM KORECYST ANT EPILEPSY AS WELL AS TRYING TO TACKLE THE VERY DIFFICULT PROBLEM OF PREVENTING EPILEPSY OR MODIFYIFYING PROGRESSION AND THE DISEASE, SO THAT'S ABOUT THE PROGRAM. STHRKS I'M PAT DAVIS, I'M A PATIENT RESEARCH ADVOCATE WITH THE PARKINSON'S DISEASE FOUNDATION SO I AM JUST LEARNING ABOUT THE--TRYING TO LEARN ABOUT THE SCIENCE BY PROFESSION. I WAS AN INTERNATIONAL CONFERENCE ORGANIZER. I HAVE DONE MEDICAL CONFERENCES BUT NOT NECESSARILY--MY LATEST JOB I WAS WITH THE WORLD BANK FOR 16 YEARS ORGANIZING CONFERENCES FOR 15,000 PEOPLE SO I GOT INVOLVED WITH THE PARKINSON'S ORGANIZATION ON THEIR STEERING COMMITTEE AND THROUGH THEM I BECAME A RESEARCH ADVOCATE. I'M ON THE OTHER END, I'M LOOKING FOR TRIALS TO PARTICIPATE IN, JUST DONE OBSERVATIONAL TRIAL HERE BUT I'D LIKE TO DO MORE PARTICIPATE NOTHING MORE TRIALS AT THE NIH. WHICH DOESN'T SEEM THAT EASY FOR SOME REASON. >> I'M MANUEL TANNIE, I'M AN OPHTHALMOLOGIST BY BACKGROUND. MY INTEREST IS INTRA CRANIAL HYPERTENSION AND THE ICRANIAL RESEARCH FOUNDATION AND WE HAVE RESEARCH PROGRAMS, AND REGISTRIES, AND WE HAVE THE SCIENCE UNIVERSITY WHERE I HAVE A CLINICAL DECISION. WE--EVERYONE DOES NOT KNOW INTERCRANIAL HYPOTENSION, I WILL TAKE A MOMENT TO EXPLAIN WHAT THAT MIGHT BE, INTERCRANIAL HYPERTENSION MEANS SPINAL PRESSURE IS TOO HIGH INSIDE YOUR HEAD, THERE ARE TWO CATEGORIES: THE OPATHIC FORM, WHICH IS A DISORDER OF OVERWEIGHT FEMALES FOR THE MOST PART IN THE CHILD BEARING YEARS. THE SECOND GROUP IS--AND WE CAN'T FIND THE CAUSE FOR THAT, AS FAR AS WE KNOW. SO WE'RE A BIT OF AN EXCEPTION OF THE GROUP IN GENERAL BEING A NONGENETIC DISORDER. THE SECOND GROUP OF PATIENTS WE DEAL WITH ARE SECONDARY IN HYPER ATTENTION AND THEY HAVE A HUGE VARIETY OF CAUSES EVERYWHERE FROM MEDICATIONS AND TRAUMA LUPUSIS, LIME DISEASE, YOU NAME ANY NUMBER OF THEM. IN ANY CASE, WE LACK TREATMENT. MANY OF OUR PATIENTS COME TO SHUNTING FOR HYDROCEPHALOUS BECAUSE THEY HAVE NO WAY TO RELIEVE THE PRESSURE INSIDE THE HEAD. THERE IS ONE OLD MEDICATION ZETAZOLOMIDE, WHICH IS USED BUT NOT VERY EFFECTIVE. IN MOST CASES. SO SURGERY IS PROBLEM. SO IN ANY CASE, I ENJOY BEING HERE AND APPRECIATE THE MEETING. THANK YOU. >> NOW I THOUGHT THAT WAS INTERESTING. >> I'M BETH, I'M THE ASSISTANT DIRECTOR FOR RESEARCH PROGRAMS FOR THE PARKINSON'S DISEASE FOUNDATION AND WE FUND A LITTLE BIT UNDER $5 MILLION IN RESEARCH EACH YEAR, WE HAVE LARGE FROMS AT COLUMBIA AND RUSH UNIVERSITY AND MOST OF THE RESEARCH IS LARGELY BASIC RESEARCH AND WE DO A LITTLE BIT OF TRANSLATIONAL AS WELL. SO I WOULD BE INTERESTED KNOWING MORE ABOUT THE NIGHT PROGRAMS WAYS IN WHICH TO TAKE SOME BASIC RESEARCH AND HAVE IT STEP FORWARD TRANSLATIONAL ALSO WE FUND A LOT OF YOUNG INVESTIGATORS, SO, THE TRANSLATIONAL R-21 MIGHT BE AN INTERESTING OPTION TO KNOW MORE ABOUT HOW OUR INVESTIGATORS [INDISCERNIBLE]. >> HI, I'M [INDISCERNIBLE] I WORK IF BLUEPRINT NEURKD--SALLY HA I IN CNS DISCOVERY I WORK IN SMALL BIOTECH, SO THAT A ENVIRONMENT TO WORK IN THIS ENVIRONMENT IN LPI, TO BRING THAT EXPERTISE TO MOVE THE PROJECT FORWARD FROM DISCOVERY OR TO DEVELOPMENT OF [INDISCERNIBLE] TO COME INTO CLINIC TO PHASE ONE. >> I'M ILENE MILLER AND I'M CONFOUNDER OF AN ORGANIZATION CALLED HOPE FOR HYPER TOMA, FOR THOSE THAT DON'T KNOW IT'S A RARE BRAIN TUMOR THAT SETS ON YOUR HYPOTHALAMUS, I'M ALSO THE PARENT OF A 13 YEAR-OLD SON WHO HAS HH, IT'S IN MANY WAYS A SPECTRUM CONDITION FROM THE STANDARD POINT THAT OUR KIDS LIKE MY SON WHO ARE VERY HIGH FUNCTIONS AND YOU WOULDN'T KNOW THEY HAD THIS CONDITION IF YOU DIDN'T KNOW TO OTHERS THAT ARE SEVERELY EFFECTED BY IT BOTH COGNITIVELY AND BEHAVIOR YEALIALLY, IT ALSO HAS THE TELL TAIL FEATURE TYPE, AND IT CAUSES WHAT LOOKS LIKE A TICK OR SPONTANEOUS, AND SO A LOT OF TIMES IT'S MISS DIAGNOSE TED OR OTHER PSYCHIATRIC CONDITIONS. OUR ORGANIZATION WHICH I HOPE TO CONFOUND NOW SIX YEARS OLD ASK WE'RE ALL VOLUNTEERS MOST OF THE FULL-TIME JAY JOBS WERE WORKING TOWARDS TRYING TO BUILD UP OUR RESEARCH PORTFOLIO SO I LOOK AT THIS AND I LISTEN TO OTHER FOLKS THAT ARE AHEAD OF US, AND LISTEN WITH ENVY, BUT I ALSO WAS HOPING MAYBE YOU COULD HELP US UNDERSTAND A LITTLE BIT ABOUT WHERE WE FIT INTO THE PORTFOLIO FROM THE STANDPOINT OF THE CONDITION ITSELF IS TYPICALLY REFRACTORY TO EPILEPSY MEDICATION AND SO, THE BEST CASE SCENARIO IS THAT KIDS ARE ELIGIBLE FOR ONE OF SERVE OF THESE IS LASER TECHNOLOGY IT'S CALLED VISUAL AID. AND I GUESS FROM THE STANDPOINT OF WHERE THE SMALL POPULATION, A RARE CONDITION, THE SURGICAL INTERVENTION WHAT MIGHT TRANSLATIONAL RESEARCH AT NIH, AND THE IT LOOK LIKE FOR AN ORGANIZATION LIKE [INDISCERNIBLE]. >> I AM DIANE, PROGRAM OFFICER WITH BRIGHT FOCUS FOUNDATION, WE FUND ALZHEIMER'S DISEASE AND MACULAR DEGENERATION, AND NEURODEGENERATION. AND YEAH, SO WE--WE PUT LAST YEAR, WE PUT OUT IN OUR CORE PROGRAM, $11 MILLION FOR ALL THREE PROGRAMS AND I WOULD SAY, WE PROBABLY HAVE 55% OR 60% BASIC, 35% TRANSLATIONAL, ABOUT 10% CLINICAL RESEARCH BUT YEAH, I'M ALWAYS LOOKING--WE DON'T ACTUALLY HAVE DIRECTED CALLS, IT'S INVESTIGATOR INITIATED BUT I'M ALWAYS TRYING TO LOOK AT OUR PORTFOLIO AND ACTUALLY I HAVE DAY-TO-DAY CONTACT WITH RESEARCHERS, AND A LOT OF THEM WANT TO KNOW HOW ABOUT HOW TO TRANSLATE THEIR RESEARCH AND SO, I GUESS, ALSO, YOU KNOW THEY PROBABLY ALREADY KNOW ABOUT YOUR GRANT PROGRAMS BUT I'M ALSO INTERESTED IN WELL ACCIDENT MAYBE IF YOU HAVE CONFERENCES OR ANY EDUCATIONAL FOR BASIC RESEARCHERS WHERE I CAN DIRECT THEM? >> HI I'M HAO WONG, AND RESEARCH DIRECTOR ON NINDS AND I OVERSEE A PROGRAM ON THE BOARD CREATE BIOFOR BIOLOGY BIOLOGICS AND WORK ON THE LEGACY TRANSLATIONAL UR-ONE PROGRAM SO I'M VERY EXCITED TO BE HERE TODAY, EITHER YOU'RE ADVOCACY PATIENT ORGANIZATION OR FOUNDING AND AS WELL AS HOW WE CAN HELP WITH WITH YOUR P. I. JUST A BIT ABOUT MY BACKGROUND, I WAS TRAINED AS A NEUROSCIENTIST AND DID POST DOC IN UCSF AND DID INDUSTRY AT MERCK IN PRECLINICAL RESEARCH, RESEARCH, AND MOVED INTO--OR DID CLINICAL DEVELOPMENT AND THEN THE LAST FIVE YEARS IN CLINICAL DEVELOPMENT SO I'M VERY EAGER TO HELP THIS IN THIS TRANSLATIONAL SPACE. WE CAN TALK ABOUT OR PROGRAM MAYBE MORE LATER BUT WE HAVE QUESTIONS, I WILL BE HERE TO HELP. >> I'M LINDA, AND I'M A PROGEC MANAGER IN THE OFFICE OF TRANSLATION RESEARCH AND RIGHT NOW LIKE HOW I MENTIONED, WE HAVE OUR NEWER PROGRAMS FOR EXAMPLE, THE GREAT BIOAND IPT GREATER INVOLVE WIDE THAT, WE ALSO HAVE A SET OF LEGACY PROGRAMS WHICH INCLUDED SMALL MOLECULES, DEVICES AND THE BIOLOGICS AND THEN, WE NOW SPLIT THEM OFF INDIVIDUALLY BUT THAT LEGACY PROGRAM IS STILL SUN SETTING, SO I'M HELPING MANAGE THOSE PROGRAMS AND YOU CAN ALWAYS DISCUSS LESSONS LEARNED OR DEPENDING ON WHAT YOU'RE INTERESTED IN. >> OKAY, SO I GUESS WE CAN MAYBE TALK ABOUT SOME QUESTIONS, THAT YOU MAY HAVE ABOUT ANY OF THESE PROGRAMS? BUT IF THERE ARE NOT, THEN THERE'S A COUPLE OTHER TOPICS I'M INTERESTED IN HOW WE CAN GET FEEDBACK ON THEM, ON JUST THINGS IN GENERAL. >> [INDISCERNIBLE]. >> I THOUGHT YOU GUYS WERE JOKING AT FIRST. THAT'S VERY FUNNY. NO I JUST WANTED TO KNOW MORE ABOUT--SO IS THE TRANSLATIONAL R21 AND THE PROGRAM THEY'RE ONE AND THE SAME. >> WELL, NO. >> AND THEN AT WHAT POINT WOULD RESEARCH BE READY FOR THIS? >> SO WE NO LONGER TAKE APPLICATIONS FOR THE TR-21. THE TWO NEW PROGRAMS THAT ARE ON THIS PART OF IGNITE ARE--HAVE BEEN IN PLACE SINCE LATE LAST YEAR, [INDISCERNIBLE] AND THE NEXT RECEIVE DATA IS COMING KNOP TWO MONTHS AND YOU CAN FIND OUT THE DATES ON ALL THIS INFORMATION INCLUDING FREQUENTLY ASKED QUESTIONS AND EVERYTHING ELSE ON OUR WEB SITE. THE ENTRY CRITERIA, REALLY IS FOR ONE, IS TO JUST HAVE AN ASSAY OF SOME SORT TO DEVELOP, THEN YOU DEVELOP, YOU CAN DO ITERATIVE SCREENING OF WHATEVER LIBRARY OR WHATEVER COMPOUND YOU MAY HAVE THAT YOU MAY BE INTERESTED IN. THE OTHER PROGRAM FOR SETTING UP OR GETTING SOME PRINCIPLE IN VIVO OR EXVIVO REQUIRES A BODY OF EVIDENCE, THAT SUGGESTS THAT YOUR PROPOSAL MAKES SENSE. AND SO, THEY COULD BE A LOT OF BLUE SKY, BUT AS LONG AS THEY'RE GROUNDED IN SOME KIND OF A BASIC SCIENCE, THEN THE ENTRY WOULD BE THERE. SO, THEY'RE MOSTLY, THE PROGRAM WAS DESIGNED SO THAT SOME OF THESE GREAT IDEAS CAN ACTUALLY BE FUNDED. AND THEN, BE CHALLENGED INTO SOME OF OUR LATER PROJECTS SO THAT THEY CAN HAVE AN EASY TRANSITION TWEENCH BASIC RESEARCH AND CLINICAL RESEARCH. OR CREATE A BLUE PRINT WE PIDE LOTS OF RESOURCES TO OVERCOME SOME OF THESE VERY EXPENSIVE TICKET ITEMS SUCH AS MANUFACTURES, SUCH AS EXTENDED IND ENABLING STUDIES, SO ON AND SO FORTH, BUT FOR GETTING A BASIC PRINCIPLE SORTED OUT, SO CAN YOU THEN MEET THE ENTRY CRITERIA AND CREATE A BLUEPRINT, THOSE ARE THE ONES THAT SHOULD BE FUNDED AND THESE ARE THREE YEAR GRANTS. THEY'RE NOT VERY EXPENSIVE THEY'RE ABOUT TWO IF I FELT THOUSAND DOLLARS A YEAR, BUT THEY'RE VERY CORE SPECIFIC, INVESTIGATORS TO IDENTIFY WHERE THE GAPS ARE AND PROPOSE SOLUTIONS AND THAT'S REALLY ESSENTIALLY WHAT THEY DO. THEY'RE NOT REALLY--AREN'T DESIGNED TO CARRY A BIG WEIGHT FOR SOME EXTENDED PRECLINICAL MODEL BUT IT'S JUST TO MAKE SURE THAT ALL THE DUCKS ARE IN A ROW SO THAT BY THE TIME YOU CONTACT HOW AND SAY, HOW I HAVE THIS PROJECT AND DEVELOPING AN ANTIBODY, YOU HAVE BEEN--HAVE A LOT OF THIS SCIENCE ALREADY IN PLACE, SO WE CAN HIT THE GROUND RUNNING, SO DOES THAT COVER EVERYTHING? >> [INDISCERNIBLE]--R-21 DOES NOT EFFECT THE PATIENTS ANYMORE. AND LAST YEAR WE DID REAND R21 WHERE YOU SEE THE PROGRAM THAT'S OVERSEEING THAT AND THEN THE LEGACY UR-ONE THAT USED TO BE SMALL MOLECULES BIOLOGICS ARTICLES AND THE ARTICLES AND WE'VE FOUND THAT TO BE MORE EFFICIENT THAT WOULD DIVIDE IT INTO THERE SO THE SMALL MOLECULES WILL GO INTO THE BLUEPRINT AND THE DEVICES ARE GOING INTO A SEPARATE PROGRAM ALL THE REST ARE IN THESE CREATE FILES FOR BIOTECHNOLOGY PROGECS, AND SO THAT STILL HAS ENLARGED A NER OF MODALITIES AND PEPTIDES AND THE THERAPIES AND SUCH. THANK YOU. >> YES, SO I GUESS, FOR ME, I GUESS IN TERMS OF, I WAS INTRIGUED WHEN YOU WERE SAYING THAT IN THE BLUEPRINT CREATE, THAT YOU HAVE--GIVE ACCESS TO MANUFACTURES AND IND ENABLING STUDIES SO IS THAT HELPING THEM T GET TOWARDS, YOU KNOW WRITING UP THE IND. AND I GUESS THIS GOES WITH MY QUESTION THAT I HAD AT THE BEGINNING IN TERMS OF DO YOU HAVE PROGRAMS LIKE EDUCATIONAL PROGRAMS FOR RESEARCHERS, I COULD DIRECT THEM TO YOU? >> SO I DON'T KNOW IF YOU'RE FAMILIAR WITH BLUEPRINT, BLUEPRINT IS KNOW EFFORT FOR ALL OF OUR INSTITUTES TO COME TOGETHER AND PUT TOGETHER FUNDING TO DO BIG PROJECTS THAT REALLY ARE RELEVANT OF NEUROSCIENCE INSTITUTES SO AS PART OF THIS, THE BLUEPRINT OR NETWORK WAS INITIATED ABOUT FIVE YEARS AGO AND THE IDEA THERE WAS MANY OF THE INVESTIGATORS THAT WERE COMING IN TO GET GRANT FUNDING JUST DIDN'T HAVE ALL THE RESOURCES TO ACTUALLY ADVANCE THEIR PROJECT BEYOND DISCOVERY. SO THESE GUYS WERE PROLIFIC SCIENTISTS WITH A LOT OF KNOWLEDGE, THOUGHT LEADERS AND THE SPACE IN THE DISEASE AREA AND BASIC BIOLOGY BUT DIDN'T HAVE THE TEAM THAT WAS REALLY REQUIRED TO HELP THEM ADVANCE THEIR PROJECT AND FORCE CLINICAL TRIALS, SO, THE MODEL WAS DESIGNED SO THAT WE DON'T JUST PROVIDE GRANT FUNDING FOR INVESTIGATORS TO THEN GO BUILD TEAMS, IT'S TO SURROUND THEM WITH ALL THE MISSING PIECES THAT MADE THEM BE AS SUCCESSFUL AS THEY CAN BE, ALSO CONSIDERING THE TIMELINES, WE WANTED TO MAKE SURE THAT THESE DISCOVERS MOVE FORWARD CLINICAL TRIALS IN AN EXPEDITIOUS WAY SO WE WANT TO MAKE SURE THAT WITHIN THE TIMELINE OR FRAMEWORK OF A FIVE YEAR GRANT OR FOUR YEAR GRANT, CAN YOU ACTUALLY GET SOMEWHERE. SO,--SO BY PROVIDING THE RESOURCES, WE THOUGHT THIS WOULD BE A PERFECT SITUATION WHERE WE CAN COMBINE THE KNOW HOW AND THE BIOLOGY SIDE, WITH THE EXPERTISEOT MANUFACTURING SIDE, LIKE YOU MENTIONED. NOW THE PROGRAM HAS EVOLVED A LITTLE BIT AS A NEWER VERSION WAS LAUNCHED LAST YEAR, INVESTIGATORS NOW CAN COME IN AND SAY, I HAVE SPECIFIC EXPERTISE AND I LIKE TO CAPITALIZE BUT I'M MISSING THAT FOLLOWING AND THEY ESSENTIALLY HAVE A LIST OF ACTIVITIES THAT THEY WANT TO DO IT INTERNALLY BUT WITH THEIR OWN TEAM BUT THE ACTIVITIES THEY WANT TO GET ACCESS TO AND ONE OF THE THINGS THAT'S COME UP OVER AND OVER, OVER THE LAST YEAR SINCE THE NEW VERSION HAS BEEN LAUNCHED IS INVESTIGATORS JUST DON'T HAVE THE RESOURCES FOR MANUFACTURE. O THE GLP TALKS TO DO THE FILING WITH THE FDA, SO THOSE ARE FOR INVESTIGATORS TO GO THROUGH WITH THIS. NOW THIS IS--HOPEFULLY THIS ANSWERS THE FIRST QUESTION, THE SECOND QUESTION IS DO WE HAVE RESOURCES IN TERMS OF EDUCATION, SO AS PART OF THE NETWORK, WE DID HAVE AN RFA AND HAVE A DHIEWRS HAPPENS ONCE A YEAR FOR INVESTIGATORS WHO GET TOGETHER ON A ANNUAL BASIS AND DISCUSS TOPICS OF THIS, SUCH AS ANIMAL, PK, TOPIC FOR DEVELOPMENT AND TOPICS RELEVANT TO TRANSLATION. NOW WE ARE TRYING TO UNDERSTAND WHETHER THIS IS ACTUALLY WORTH WHILE ENDEAVOR FOR US TO CONTINUE AND INTERNALLY WE HAVE SEVERAL DISCUSSIONHOW BEST TO SET UP A CONFERENCE THAT WOULD SORT OF PROVIDE THIS INFORMATION AND ASHES LOW INVESTIGATOR'S TO COME IN AND TALK TO FIELD EXPERTS ABOUT THEY MAY WANT TO BOUNCE AN IDEA OFF OF, OR TO TALK ABOUT THINGS THEY REALLY ARE NOT AN EXPERT. SO WE HAVE SOME IDEAS ABOUT HOW TO DO THIS BUT FEEDBACK WILL BE CRITICAL AT THIS STAGE AS SORT OF A WHITE PAGE EXERCISE TO FIGURE OUT WHAT WOULD MAKE SENSE, WHAT IS IT THAT YOU WOULD LIKE TO SEE THAT WOULD THEN ALLOW YOU TO REALLY PUT PEN TO PAPER AND WRITE DOWN PROPOSAL OR WHAT WOULD YOU DO FOR THE FUNDING BEYOND JUST A DOLLAR AMOUNT WELL, WELL WE RECOGNIZE AS MONEY JUST IS NOT ENOUGH, SO YOU NEED TO COMBINE MONEY WITH KNOW HOW AND THE EXPERTISE, SO AS PART OF THIS, HOUSE PROGRAM AND IN THIS PROGRAM ARE KIND OF MOVING ALONG THAT WAY, TOO, AND THEY THINK ABOUT THAT AND PROVIDE RESOURCES BEYOND THE GRANT DOLLARS AND THESE ARE ALL EXPERIMENTS. THEY MAY WORK REALLY WELL AND WE MAY DECIDE THAT THIS IS THE PERFECT DIRECTION TO G TOWARDS BUT WE MAY SIT DOWN AND VARIOUS MEETINGS LIKE THIS AND GET A FEEDBACK AND MAYBE THIS IS NOT A BEST WAY TO DO IT. SO FEEDBACK WILL BE CRITICAL FOR US. >> AND JUST AS YOU WERE TALKING, JUST LAST YEAR, OUR SRC, BASICALLY THIS PROGRAM OR ANY KIND OF FEEDBACK THAT CAN YOU GIVE TO THE GENERAL SCIENTIFIC COMMUNITY WOULD HELP IMPROVE THE QUALITY OF APPLICATIONS THAT WE RECEIVE BECAUSE YOU KNOW OUR SCIENTIFIC COMMITTEE IS SAID, OH, WELL, YOU KNOW WE NEED THE PK DATA AND A NUMBER OF PEOPLE IN THE DRUG DISCOVERY PROJECT WITH PROPOSALS THAT ARE NOT SUBMIT THANKSGIVING AND WE WANT IT AND SO PEE PUT ON OUR INNERSTRUKSES TO OUR APPLICANTS THAT WE HAVE TO HAVE THAT FOR DRUG DISCOVERY PROJECT AND SO IF T'S MORE AWARENESS OR MORE HELPING OF WRITING GRANTS JUST FROM YOU GUYS TO HELP IMPROVE THE QUALITY OF APPLICATIONS, THAT WOULD BE HELPFUL. >> SO A WELL WRITTEN PROPOSAL GOES A LONG WAY PERSUADING THE REVIEWER TO GIVE IT THE THUMBS UP SO THAT PART IS REALLY CRITICAL AND SURROUING THE EYES OF THE CRITICAL THINKERS FROM DIFFERENT FIELDS WOULD REALLY ALLOW INVESTIGATORS TO REALLY THINK ABOUT THE PROPOSALS IN DETAIL AND TRY TO FIGURE OUT WHAT WOULD MAKE SENSE AND WHAT WOULD MAKE A CASE FOR WHY A PROJECT IS SIGNIFICANT AND WHY IT SHOULD BE FUNDED. AGAIN ON THE TRAINING SIDE, THAT'S SOMETHING WE WOULD LIKE TO WORK TOWARDS AND ONE OF THE REASONS WOULD BE TO GET BETTER PROPOSALS, THERE'S OBVIOUSLY SOME REALLY GOOD SIGNS, AND THE BASIC SCIENCE LEVEL. THERE IS SOME RESISTANCE FOR SOME INVESTIGATORS TO MOVE INTO TRANSITION BECAUSE THAT'S NOT THEIR COMFORT ZONE. RIGHT? AND ALSO THE RESISTANT ALSO COMES FROM THE FACT THAT THEY'RE NOT FAMILIAR WITH THE CHALLENGES AND SO, SOME LEVEL OF INFLAMMATION, SOME LEVEL OF TRAINING THAT CAN BE PROVIDED TO INVESTIGATORS WOULD BE QUITE CRITICAL FOR US AND WE--WE ARE AT THE STAGE OF BRAINSTORMING WE ARE TRYING TO FIGURE OUT WHAT WOULD WORK REALLY LUNFORTUNATELY WITH THE LIMITED RESOURCES WE VWE JUST DON'T--WE CAN'T UNFORTUNATELY HAVE ALL OF THE THINGS IN PLACE. I KNOW OUR COLLEAGUE'S WITH NCATS ARE THINKING ABOUT PUTTING TOGETHER WEBINARS AND WEBCASTS THAT ARE A WEB SITE AND THEN YOU COULD BE FAXED TO ANY POINT, IT WOULD BE LIKE AN HOUR LECTURE ON SPECIFIC TOPICS. AND WE HAVE TO THINK ABOUT WHETHER THOSE MAKE SENSE OR NOT. >> ONE THING I'M HEARING IS, ALL THESE RESOURCES HERE AND NOBODY NEEDS THEM UNTIL THEY NEED THEM AND I THINK LIKE SO MUCH IN LIFE, IT'S NOT UNTIL YOU HAVE THE QUESTION IN YOUR MIND THAT YOU'RE READY TO ABSORB THE ANSWER. SO YOU COULD SIT THROUGH, YOU KNOW THIS AS MANY TIMES AS YOU WANT, UNTIL HAVE YOU THE RIGHT ASSAY OR UNTIL YOU HAVE, YOU KNOW THE DEVICE TO BE ADVANCED OR WHAT OUR NEEDS OR ADDITIONAL CHEMISTRY OR WHATEVER THE SPECIFIC ISSUE IS, YOU WILL NOT UNDERSTAND YOUR ANSWER TO THE POINT WHERE YOU'RE GOING TO REMEMBER IT WHEN YOU NEED IT I THINK RECORDING THE WEBINAR COULD BE AN EXCELLENT IDEA AND THE ANSWER'S THERE WHEN PEOPLE ARE READY TO ASK THE QUESTION. >> COULD YOU EXPOUND A BIT ON TTE DEVICES PROGRAM? MY INTEREST IS OUR DISORDER, WE CAN ONLY MEASURE INTERCRANIAL PRESSURE BY INVADING THE BODY EITHER THROUGH A BURR HOLE AND ENTERING THE BRAIN AREA OR SPINAL TAP. BUT WE HAVE NO WAY OF NONINVASIVELY MEASURING THIS INTERCRANIAL PRESSURES. WHAT IS YOUR CREATIVE DEVICE PROGRAM IF CAN YOU JUST EXPOUND ON THAT A BIT. >> SO THE PROGRAM DIRECTOR FOR DEVICES IN GENERAL UNDER SBIR, AND UNFORTUNATELY, HER NAME, AND SHE WILL BE THE RIGHT, HER SENSE TO TALK ABOUT THIS, SO I KNOW THERE ARE CERTAIN TOPICS SUCH AS MEASUREMENTS AND THINGS THAT YOU MENTIONED, ARE NOT NECESSARILY WITHIN A SCOPE OF DEVELOPMENT OF THE PROCESS THAT ARE THERAPEUTIC AND HAVE A THERAPEUTIC ANGLE BUT THE RIGHT PLACE IS TO ESSENTIALLY PULL UP THE P. A. R. AND LOOK AT END SCOPEAC IV THERAPIES AND OUT OF SCOPE ACTIVITIES AND TRY TO FIGURE OUT WHETHER THE TYPE OF THINGS THAT--TYPE OF RESEARCH THAT WE'RE DOING FITS WITHIN THE SCOPE OF THE GLAND FOR DEVICES IF YOU HAVE ANY QUESTIONS EITHER COME TO EITHER ONE OF US OR GO DIRECTLY TO STEPHANIE TO GET THE UNEQUIVOCAL ANSWER AS TO WHETHER YOU SHOULD WRITE THE APPLICATION OR NOT. SO, THAT--FIVE MINUTE CONVERSATION WITH STEPHANIE IS THE TOPIC IN HER OFFICE WOULD BE QUITE CLEAR. >> SO DEVICES, THEY HAVE THREE DIFFERENT PROGRAM ANNOUNCEMENTS RIGHT NOW AND DEPENDING ON WHAT THE DEVICES ARE FOR, SO THEY HAVE A PATH FOR A 510 K AND TELL BE MORE OF A RESEARCH DEVICE AND I CAN'T REMEMBER WHAT THE THIRD ONE IS NOW, AND PMA ARUAL SO THEY KIND OF SPLIT IT AND EACH ONE HAS CERTAIN REQUIREMENTS SO A LOT OF IT YOU NEED TO HAVE PRESUBMISSION MEETINGS WITH THE FDA, AND FOR THEIR GATE, SO THAT THEY CAN KIND OF MAKE SURE, OH, THANK YOU, HE HAS IT UP THERE. >> SO DEPENDING ON WHAT YOUR PROJECT IS, YOU--LIKE, THEY SAID YOU CAN GO INTO THE SPECIFIC FUNDINGLY ANNOUNCEMENTS THEY CAN READ THE ENTRY OR EXIT KRIST TERYARKS A LOT OF THEM REQUIRE BEFORE YOU ENTER THAT YOU HAD A PRESUBMISSION WITH THE FDA, AND RLY WHAT THAT'S FOR IS A LOT OF PEOPLE COME IN AND THEY'RE LIKE, OH THIS IS WHAT I WANT TO DO. BUT THEN IF YOU FUND THE GRANT, YOU TALK TO THE FDA, IT'S ACTUALLY, YOU NEED MORE STEPS. SO WHEN YOU'RE FUNDING A GRANT, IT'S BETTER FOR US, STRONGER IF YOU'VE HAD CONVERSATIONS WITH IT IS FDA, YOU KNOW EXACTLY WHAT STUDIES NEED TO BE DONE SO CAN YOU BUDGET APPROPRIATELY, YOUR TIMELINE CAN BE APPROPRIATE AND AT THE END, CAN YOU GET TO YOUR IDE AND BE ABLE TO DO THE CLINIC SO IT'S SET UP, SOME OF THOSE REQUIREMENTS ARE SET UP FOR A REASON AND LIKE YOU SAID, SOME THINGS IN PARTICULAR, TALK TO STEPHANIE ABOUT. SHE WOULD KNOW THE INS AND OUT. >> JUST A AS FOLLOW UP TO YOURS AS WELL, DEPENDING ON WHAT THE INDICATION IS, FOR EXAMPLE, SOME THINGS ARE ARE THERAPY, STEVE BERG HAS A LOT OF PRERECORDED THINGS ON THE WEB SITE THAT ARE EDUCATIONAL FROM A REGULATORY PERSPECT. OTHER INSTITUTES AS WELL, SO FOR EXAMPLE, NHLBI AS A SMALL BUSINESS PROGRAM AND THEY ARE WEBINARS MA ARE COMPANIES LOOKING FOR WE'VE HAD THE INSTITUTE OF HOW IT HOPERATES IN THIS THING WHICH IS HARDOT OSIDE WORLD OF AND THE NHLBI IS BENEFICIAL FOR OUR NINDS, TO LEARN. SO THERE ARE WOO RESOURCES LIKE THAT. >> SOPHISTICATED ADD ON TO THAT, TOO, WE ARE--WE GOING TO BE PROVIDING SOME LINKS IN OUR WEB SITE AS WELL BUT WE ARE ALSO CONSIDERING TRY TO ACTUALLY SNAPSHOT WHAT WILL BE MOST HELPFUL WITH THE PI, SO MANY TOPICS HAVE THE RESPONSE: OKAY, WHERE DO WE START. I'LL GIVE YOU MY CARD AFTER THIS BUT IF YOU HAVE SUGGESTIONS ABOUT WHERE IS THE MOST NEEDED IT IF WE DECIDE A GOOGLE HANG OUT OR A WEBINAR. BEFORE THE BIGGER INITIATIVES COMING IN, THIS WILL BE THE MORE SHORT, LIKE ADDRESS MOST FREQUENTLY ASKED QUESTIONS, WHERE WOULD WE START, WE REALLY WOULD APPRECIATE IT. >> WE DEVELOPED LAST YEAR, HOW CHAMPIONED--THIS DECISION TREE DOWN HERE ON OUR WEB SITE, WHICH I'M NOT SURE IF IT'S GETTING ENOUGH TRAFFIC BUT I'M GOING TO BRING THIS UP HERE, SO IF YOU'RE INTERESTED FOR A SPECIFIC DESIGN OR A SPECIFIC DEVICE YOU WANT TO BUILD OR IF YOU'RE INTERESTED IN BIOLOGICS OR SMALL MOLECULES AND YOU GO TO OUR WEB SITE AND SAY, WELL, IS THERE FUNDING ANNOUNCEMENT THAT WILL COVER THIS? WE'RE HOPING THE DECISION TREE WILL HAVE AN ANSWER FURTHER AND BY CLICKING ON BASIC QUESTIONS, YOU CAN GET DIRECTED TO THE SPECIFIC P. A. R. THAT WOULD THEN BE EXACTLY WITHIN THE SCOPE OF WHAT IT IS YOUR TRYING TO DO. SO THIS IS--THESE ARE SOME OF THE INFORMATION THAT WE'RE PUTTING OUT THERE, BEYOND JUST READING OUR PRs WHICH ARE SOMEWHAT TRICKY TO READ, THEY'RE NOT THE BEST, YOU KNOW BED TIME READINGS, BUT, BEYOND THAT IF YOU WENT TO THAT AGAIN AND JUST WANTED TO LEARN ANY--ANYMORE BEYOND WHAT'S LISTED HERE, YOU ESSENTIALLY CAN GO TO A SUBSET, BY JUST CLICKING ON THE NAME OF THE PROGRAM ASK THAT WILL TAKE YOU TO THE OFFICIAL PAGE THAT COVERS THAT PROGRAM AND WITHIN EACH PROGRAM, WE HAVE FREQUENTLY ASKED QUESTIONS. AND WE HAVE EXAMPLES OF SOME THAT YOU HAVE TO GIVE A FORM OR USE TO SORT OF THE POSITION THEIR APPLICATIONS. SO ANYMORE QUESTIONS, I KNOW WE ONLY HAVE A FEW MORE MINUES LEFT BUT IF THERE ARE--NOT IF NOT MAYBE WE CAN TAKE A QUICK BREAK? WELL IT'S TOTALLY UP TO WHETHER YOU WANT TO--[INDISCERNIBLE]. OKAY, SO WELL, THANKS AGAIN FOR JOINING US. I GUESS WE'RE GOING TO HAVE TO RECONVENE HERE AT 4:00 WITH THE NEXT SESSION, THEY WILL HAVE TO SORT OUT THE CHAIRS AND REPORT BACK. >> I THINK WE'RE READY TO GET STARTED AND FINISH UP. I THOUGHT IT WAS A GREAT MEETING, I APPRECIATE EVERYBODY'S INPUT, I WE COVERED THE ENTIRE WATER FRONT OF BASIC TO CLINICAL, IT'S A LOT. AND I APOLOGIZE FOR FATIGUING EVERYONE'S BRAINS OUT TODAY WITH ALL THE THOUGHTS THEY HAD TO PUT OUT. BUT I THINK THIS IS THIS WAS VERY VALUABLE, WE CAN DO DEEP DIVES NEXT TIME. WE CAN THINK ABOUT RESOURCES OR WORK WE CAN DO IN THE TIME IN BETWEEN THE MEETINGS, AND TRY TO HELP THE NONPROFITS KIND OF GET AT THE SAME LEVEL OF INTERACTION THAT THEY GOT HERE TODAY, ON KIND OF A MORE REGULAR BASIS. THAT'S A THEME THAT RAN THROUGH THE DAY. AND SO, RIGHT NOW, WHAT WE WOULD LIKE TO DO IS JUST HEAR FROM THE BREAK OUT LEADERS WHAT KIND OF ADDITIONAL POINTS CAME UP IN THE BREAK OUT GROUPS WITH REGARD TO THE TOPICS. OF THE MEETINGS THE LAST TWO DAYS, SO RON AND ILENE, DO YOU WANT TO START OFF AND GIVE US A BRIEF RUN DOWN OF THE MEETINGS. THIS IS THE BASIC GROUP FOR THE STRATEGIC PORTFOLIO. >> SO RON AND I TOOK NOTES AND WE'LL OFFER A COUPLE OF INSIGHTS FROM I ATTENDED THE FIRST SESSION AND RON ATTENDED BOTH. A COUPLE QUESTIONS AND SUGGESTIONS THAT CAME UP WERE TO THINK ABOUT WHO ARE THE SCIENTISTS THAT YOU'RE RECRUITING TO YOUR BASIC SCIENTIST AND HOW DO YOU KNOW IF THEY'RE GOOD AND PUBLICATION CERTAINLY IS ONE WAY TO EVALUATE THAT BUT TO NOT LET THAT BE THE ONLY WAY OF EVALUATING THAT TO REALLY NETWORK AND TO ASK PEOPLE YOU KNOW BOTH INSIDE ACADEMIA AND INDUSTRY AND OTHER SOURCES TO HELP YOU IDENTIFY PEOPLE THAT EITHER HAVE AN INTEREST DIRECTLY IN YOUR AREA OF RESEARCH BUT ALSO PEOPLE THAT MIGHT BE TANGENTIALLY RELATED. THAT COULD BRING A NEW PERSPECTIVE AND I THOUGHT THAT WAS A HELPFUL POINT OF VIEW. ANOTHER SUGGESTION THAT WAS MADE WAS ONCE YOU'VE IDENTIFIED SOME BASIC RESEARCHERS, TO VISIT THEM IN THEIR FACILITY. TO EVEN TAKE, YOU KNOW YOUR SCIENTIFIC ADVISORY BOARD TO THEIR LAB AND ASK THEM ABOUT THEIR PORTFOLIO AND RESEARCH AND THE ENVIRONMENT AND EXPERTISE AND WHERE IT'S BEING DONE AND TAKEN--THEY'S A TREAT FOR THE BOARD MEMBERS TO SEE HOW THEY'RE EACH OPERATING BACK AT THEIR OWN INSTITUTION, AS WAYS TO NOT ONLY IDENTIFY AND SEE THE RESEARCH BUT GROW IT AND CREATE THAT COMMUNITY AND OTHER SUGGESTIONS FOR DOING THAT, ONE OF THE OTHER AND I'LL STOP WITH THE THIRD ONE THAT WAS INTERESTING, IS WHEN YOU THINK ABOUT YOUR GRANT PORTFOLIO AND YOU'RE SEATING IN THE RESEARCH IN THIS CUTS ACROSS ALL DIFFERENT TYPES OF RESEARCH, ORGANIZATIONS NIGHSATIONS TEND TO THINK ABOUT IT AS A PERCENTAGE WILL BE ATTRIBUTED TO BASIC PERCENTAGE WILL BE ATTRIBUTED TO TRANSLATIONAL AND A PERCENTAGE WOULD BE ATTRIBUTED TO CLINICAL RESEARCH CONTINUUM OF AGE THAT IN HIS POPULATION TWO YEARLYS THAT WERE DIAGNOSED WITH A PARTICULAR DISEASE HE WAS COVERING HAD VERY DIFFERENT NEEDS AND FROM BEING ABLE TO COMMUNICATE YOUR RESEARCH PORTFOLIO, BOTH TO THE PUBLIC AS WELL AS TO POTENTIAL FUNDERS, IT WAS IMPORTANT TO MAKE SURE YOU COVERED THE SPECTRUM OF PEOPLE WITHIN YOUR PORTFOLIO, THAT WERE IMPACTED BY THAT DISEASE BECAUSE, YOU KNOW WHAT'S GOING TO BE IMPORTANT TO SOMEBODY WHO'S NEWLY DIAGNOSED IN THIS THERAPEUTIC INTERVENTIONS MAY NOT BE AS KEY AS IMPORTANT TO SOMEBODY WHO'S FURTHER ALONG IN THEIR DIAGNOSIS AND PERHAPS JUST FEELING AT THE END OF LIFE OR MANAGEMENT OR OTHER TYPES OF ISSUES. SO HE SUGGEST WIDE YOU'RE THINK BEING THE DIFFERENT MODELS TO COME UP WITH CONSTRUCTS THAT WILL BE HELPFUL IN FORMULATING DIFFERENT TYPES OF RESEARCH. >> GREAT, I WOULD LIKE TO OFFER A FEW COMMENTS TO REENFORCE WHAT EILEEN IS JUST REPORTED AND ADD A COUPLE OF THINGS FROM THE SECOND BREAK OUT SESSION FIRST THERE'S A REAL EMPHASIS IN BOTH BREAK OUT SESSIONS IN THE IMPORTANCE AS NINDS COLLEAGUES WITH THE TEST TO GROWING THE NEXT GENERATION OF INVESTIGATORS IN YOUR DISEASE SO MUCH EMPHASIS HERE AT THE NIH AND NINDS IN PARTICULAR, ON, AND AND WE CAN'T ALLOW THAT SO HOW DO YOU ATTRACT THEM, IDEAL MENTIONED A COUPLE OF WAYS, SOME OTHER IDEAS CAME UP INCLUDED THAT CAN YOU ATTRACT SOME INVESTIGATORS BY SIMPLY TELLING THEM YOUR STORY. CAN YOU ATTRACT OTHERS BY OFFERING FUNDING. YOU CAN ATTRACT AND IMPRESSING HIM WITH THE NOTION THAT THEY CAN REALLY BE IMPACTFUL THAT AND THE STAR IN YOUR HEAVEN AND ATHER POINT THAT WAS MADE S&P THAT THE PROGRAM DIRECTORS HERE AT THE NINDS WOULD BE HELPFUL AND ESPECIALLY IN THE BEGINNING STAGES OF YOUR ORGANIZATION, IN MY PARTICULAR CASE ISSUE FOR EXAMPLE, PROGRAM DIRECTOR WE MET WITH RIGHT AWAY, WAS HELPFUL IN OOH DENTIFYING THE KEY SCIENTISTS THAT WERE THE GROWING STARS IN THE FIELD AND ONE OF THEM THAT SHE ADENTIFIED BECAME A MEMBER OF OUR BOARD OF DIRECTORS OR SCIENTIFIC REVIEW COMMITTEE CHAIR AND THE HEAD OF OUR SCIENTIFIC BOARD SO YOUR PROGRAM DIRECTORS CAN BE VERY--THEY KNOW YOUR FIELD AND SO CONSULT THEM AT THE OUTSET AND THROUGHOUT YOUR EXPERIENCE. THE PROGRAM DIRECTOR IN THE ROOM AND THE SECOND MEETING AND THE FIRST MEETING, I'M SORRY, IN FACT SAID ONE OF THE THINGS WE NEED DO IN OUR RESEARCH IS REDEFINE SUCCESS, SO MANY OF US, YOU HAVE YOUR GENE, YOU WANT THE CURE TOMORROW AND WE ALL HAVE THAT IMPULSE, BUT YOU'RE NOT GOING TO GET THE CURE OUT OF YOUR FIRST CLINICAL TRIAL. AND YOU HAVE TO REDEFINE WHAT SUCCESS LOOKS LIKE. AND I WOULD SUGGEST YOU HAVE TO REDEFINE WHAT FAILURE LOOKS LIKE AND TRY AND NOT SEE IT EVER. THERE'S NO SUCH THING IN MY VIEW, AS A WELL DESIGNED CLINICAL TRIAL THAT FAILS. YOU WILL LEARN SOMETHING FROM EVERY CLINICAL EXPERIMENT IF IT'S WELL SUFFICIENTLY WELL DESIGNED, HAS ROBUST PRECLINICAL DATA. THE COMPLETE STRESSOT IMPORTANCE OF THE THINGS WE TALKED ABOUT YESTERDAY AND TODAY. A PATIENT REGISTRY THAT CAN BE USED AS CONTACT REGISTRY TO RECRUIT YOUR CLINICAL TRIALS AND YOUR BASIC RESEARCH PARTICIPATION AND BIOREPOSITORYS, ALL THESE WAYS IN WHICH PATIENT GROUP CAN REALLY ASSIST THE RESEARCH ENTERPRISE AND CAN REALLY ATTRACT PHARMACEUTICAL PARTNERS, AND THERAPY PARTNERS TO YOUR SIDE. VERY IMPORTANT TO MAKE SURE WHEN YOU DO CLINICAL RESEARCH, THE RESULTS ARE MADE AVAILABLE. TOO MANY TIMES CLINICAL TRIALS ESPECIALLY IF IT'S SPONSORED BY PHARMA IS CONSIDERED A FAILURE, THEY'RE NOT GOING TO ADVANCE THE DRUG, THEY ARE RELUCTANT TO SHARE THE NEGATIVE DATA, AND SO FROM THE NIH'S TREMENDOUS EMPHASIS ON SHARING NEGATIVE DATA BECAUSE AGAIN THERE'S NO SUCH THING, WE WILL LEARN FROM IT ALL. JUST ENCOURAGE YOU ALL TO TAKE THAT APPROACH WITH YOU. THE RESEARCH THAT YOU FUND SO IMPORTANT TO GET YOUR INVESTIGATOR'S TOGETHER AT THE OUTSET AND THROUGHOUT YOUR EXPERIENCE, THERE'S SO MUCH COLLABORATION THAT SPRINGS FROM GETTING THEM TOGETHER, THERE'S SO MUCH SHARING WHICH IS ANOTHER POINT OF INTEREST, SHARING THE DATA AT OUR FIRST MEETING, WE HAD--WE WERE THE FIRST INTERNATIONAL SCIENTIFIC CONFERENCE IN OUR DISEASE, AND WE HAVE INVESTIGATORS THAT LOOKED ACROSS THE TABLE FROM ONE ANOTHER AND SAID, I'VE BEEN READING YOUR PAPERS FOR YEARS, I'M JUST SO THRILLED TO BE IN THE ROOM WITH YOU AND YOU KNOW THAT IF THAT'S THE CASE THERE ARE ABOUT 18-24 MONTHS BEHIND THE POWER CURVE, NOW WE HAVE A CONFERENCE LIKE THAT AND THESE PEOPLE ARE ON THE PAPER. THEY'RE NOT READING THE PAPER, THEY'RE ON THE PAPER AND THAT'S THE KIND OF COLLABORATION YOU NEED AND NOW IT'S HARD FOR US TO RECRUIT PEER REVIEWERS, FOR OUR PROJECTS BECAUSE THE FIRST FIVE ASK, THIS IS GREAT SCIENCE BUT I'M ON THE TEAM SO CAN'T HELP YOU. FINALLY IT'S VERY IMPORTANT, THE QUESTION WAS RAISED ABOUT HOW YOU CAN INFLUENCE, AND EVEN SHAPE YOUR RESEARCH PORTFOLIO. AND THE VARIOUS SOLUTIONS THAT WERE OFFERED, ONE WAS TO--YOU IDENTIFY A KEY NEED IN YOUR DISEASE SPACE. YOU FORM A CONSORTIUM AROUND THAT NEED AND YOU GET COLLABORATIVE FUNDING, FUNDING TO FUND THIS SOLUTION. SO IN OUR CASE, WE ALL NEED BIOMARKERS, WE FORMED A CONSORTIUM AROUND BIOMARKERS AND INCLUDES ABOUT THREE DRUG COMPANIES, AND A GOOD NUMBER OF ACADEMIC INVESTIGATORS THAT HAVE VARIOUS APPROACHES FORMING BIOMARKERS IN OUR FIELD. THEY'RE ALL FUNDED BY THIS CONSORTIUM, SO THAT'S ONE WAY YOU CAN REALLY SHAPE YOUR RESEARCH PORTFOLIO. ANOTHER IS TO HAVE THESE MEETINGS. GET THEM TOGETHER, GET THEM TO SAY, WHAT THEY FEEL THEY REALLY NEED AND FORM LARGE MEETINGS TO DO THAT, FORM SMALL MEETINGS AROUND PARTICULAR ISSUES, LIKE BIOMARKERS OR ANIMAL MODELS OR CINICAL TRIAL DESIGNS AND SO FORTH. AND THEN, IN THOSE MEETINGS YOU CAN IDENTIFY NEXT STEPS AND OFFER A GRANT TO MEET THAT NEED THAT SPRINGS RIGHT OUT OF THE MEETING AND FINALLY I'LL SAY THAT LAURA MAGMAMUS, TALKED ABOUT THE IMPORTANCE TO NINDS OF THE PARTNERSHIPS WITH YOU. SO THIS ISN'T A ONE WAY FEED AT THE TROUGH SITUATION, THIS IS A TWO WAY STREET HERE AND MY FINAL COMMENT WOULD BE TO APPLAUD AND ASK YOU TO APPLAUD THESE WONDERFUL NINDS MANAGEMENT AND STAFF AND THEY'RE IN FOR ALL OF US. [ APPLAUSE ] >> OKAY AT THE TIME. LOOK AT THE TIME, WALTER AND HIS WHOLE STAFF SPENT WITH US THE LAST TWO DAYS, THESE ARE VERY BUSY PEOPLE AND IT WASN'T JUST THE LAST TWO DAYS, THEY WERE ON EVERY STEERING COMMITTEE, WALTER'S CHAIRED EVERY STEERING COMMITTEE CALL AND THERE'S OTHER PEOPLE IN THE ROOM THAT CAN ATTEST TO THAT SO THESE GUYS ARE ALL IN FOR ALL OF US, THANKS. [ APPLAUSE ] >> SORRY FOR GETTING EMOTIONAL. >> OKAY, NEXT, [INDISCERNIBLE]. >> I LISTEN TO ILENE AND RON AND THEIR DETAILED NOTES AND I'M STRUCK BY I THINK OUR DISCUSSION REALLY GENERATED A WHOLE LOT MORE QUESTIONS THAN ANSWERS, YOU GUYS CAME OUT WITH EYE NICE TO DO LIST OF SOLID ANSWERS, IT SEEMS TO ME. I THINK LIKE THE SESSIONS BOTH DAYS WE HAD A HEFTY REPRESENTATION FROM NONPROFITS TO VARIOUS POINTS IN THE SPECTRUM OF TRANSLATIONAL SCIENCE, CLEARLY SOME PEOPLE WHO YOU KNOW AREN'T EVEN READY TO THINK ABOUT THAT SPOT YET. AND THEN AT THE OTHER END SOME OF THE FOR-PROFIT FRIEND WHO IS HAVE PARTNERED SUCCESSFULLY AND COULD TESTIFY TO THE VALUE AND RESOURCES NINDS CAN OFFER. I DO WANT TO SAY WE HAD A REALLY PHENOMENAL REPRESENTATION FROM OUR OFFICE OF TRANSLATIONAL RESEARCH AND IT WAS NICE TO HEAR FROM THOSE PROGRAM OFFICERD TO LEARN MORE ABOUT THE SPECIFIC PROGRAMS THAT NINDS IS OFFERING WHEN YOU GET TO THAT POINT TO NEED SOME OF THOSE PIECES THAT YOU'RE INVESTIGATOR'S MAY NOT BRING TO THE TABLE, THEMSELVES. THEMES THAT CAME OUT FOR ME AND I KNOW AMIR HAS NOR SPECIFIC NOTES BUT COMMUNICATION, AGAIN, THAT'S NO REVELATION TO ANY OF US. BUT JUST GETTING TOGETHER LIKE THIS OR PICKING UP THE PHONE, IT'S STRIKING TO ME TO PEOPLE WOULD WANT TO GET A CALL TO ME AND WELCOME THAT IT CAN LEAD TO A WHOLE LOT MORE. ALSO JUST THE VALUED PARTNERSHIP AS RON JUST SAID, I THINK WE SAW THAT ACROSS THE SPECTRUM. MY FINAL NOTE IS I THINK WE HAD A REALLY GOOD DISCUSSION ABOUT HOW PEOPLE CAN FIND INFORMATION WHEN THEY'RE READY TO ABSORB IT. I THINK IT'S ONE THING TO HAVE LONG DISCUSSIONS RIGHT NOW ABOUT SOME MEDICAL--SOME DEVELOPMENT OF MEDICAL DEVICE FOR INSTANCE AND IF I DON'T HAVE A PROGRAM OR A PROJECT THAT'S ASKING THAT QUESTION RIGHT NOW, I'M NOT REALLY GOING TO ABSORB THE ANSWER OR THE DETAILS ON HOW TO MAKE THAT HAPPEN. SO WE DID HAVE A DIGS CUSHION ABOUT RECOLLECT WAYS LIKE WEBINARS THAT CAN BE RECORD AND THINGS LIKE THAT SO THAT YOU GUY CANS BE MORE EFFICIENT IN PUTTING OUT THE INFORMATION AND IT'S THERE AND RECORDED AND READY FOR THE AUDIENCE WHENEVER THEY'RE READY TO RECEIVE THE INFORMATION. >> SO ALONG THOSE LINES I THINK WE--WE CREATED SIX DIFFERENT BUCKETS, THROUGH WHICH HOPEFULLY WE WILL HAVE MORE ADDITIONAL INFORMATION AS SUSAN MENTIONED WE CAME UP WITH QUESTIONS AS OPPOSE TO SOLUTIONS AND I THINK THAT'S A GOOD STEP FOR US TO GO OUT AND TALK TO YOU AGAIN AT OTHER FORMATS AND OTHER FORUMS TO RECEIVE HONORS EMPLOYEES HONEST FEEDBACK ON HOW WE CAN IMPROVE THE ORGANIZATION AND PROCESSES SO I WILL QUICKLY GO THROUGH THIS. SO FOR US, ONE OF THE TOPICS WAS HOW TO PRIVATE ORGANIZATIONS PARTNER WITH NIH FUNDED INVESTIGATORS AND PREJUDICE ECTOMYOSINS WE TALK ABOUT VARIOUS VENUES WE HAVE THROUGH WHICH WE A LOT OF PEOPLE CAN ACTUALLY SEARCH THROUGH OUR FUNDED PROJECTS AND LOOK AT WHAT'S BEING FUNDED AND LOOK AT ABSTRACTS, THAT ARE PUBLICLY AVAILABLE. THE EXAMPLE CAME UP FOR CYDAN AND NCATS TO PARTNER UP AND IT TURNED OUT IT WAS A SERENDIPITOUS PARTNERSHIP WHERE THE INFORMATION WAS NOW COMMONLY AVAILABLE TO CYDAN AND THEY HAD TO ACCIDENTALLY RUN INTO THE INVESTIGATOR TO MAKE THAT PARTNERSHIP HAPPEN. WHICH IS REALLY IRONIC BECAUSE WE FUND MANY PROJECTS THAT ARE EXCELLENT AND WE HOPE THERE IS A HANDOFF AT SOME STAGE WITH GROUPS LIKE CYDANAND WE NEED TO COME UP WITH WAYS OF FACILITATING THAT SECOND QUESTION IS HOW DO INVESTORS APPLY FOR THAT BEYOND FUNDING AND THE IDEA OF PROVIDING RESOURCES BEYOND GRANT FUNDING SEEMS TO RESONATE WITH A LOT OF OUR PEOPLE HERE, AND FOR EXAMPLE, THE GROUP THERAPEUTICS NETWORK AND THE RESOURCES FOR IND STUDYING AND MANUFACTURING AND CONSULTANCIES AND THINGS LIKE THAT WHERE WE BUILT TEAMS AROUND INVESTIGATORS SO THEY CAN BE AS SUCCESSFUL AS THEY POSSIBLY CAN BE WITH THE IDEA SEEMS TO RESONATE AND WORK QUITE WELL, SO THAT'S ACTUALLY GREAT FEEDBACK FOR US AND WE HOPE TO CUE THIS PROGRAM AND EXPAND ON ANOTHER ONE IF AT ALL POSSIBLE. NUMBER THREE WAS CAN WE APPLY FOR GRANTS WHERE SOME COST SHARING IS PROVIDED INVESTIGATORS DO GET PRIVATE FUNDING AND THEY DO LEVERAGE THAT OVER THE LAST COUPLE OF DAYS, HOW TO LEVERAGE SOME SMALL AMOUNT OF FUNDING TO DO INVESTIGATIONAL WORK CAN COME IN FOR THREE DIFFERENT AIMS ONE OF WHICH IS FUBBEDDED THROUGH A PRIVATE ORGANIZATION AND SO, THESE ARE THE THINGS THAT PERHAPS WE'VE TAKEN FOR GRANTED. THESE ARE CERTAINLY AVAILABLE AND THIS INFORMATION NEEDS TO GET OUT THERE SO THAT EVERYBODY'S FAMILIAR WITH THEM. AS FAR AS WHAT KIND OF EDUCATIONING OR TRAINING IS PROVIDED AND WE'VE BEEN TALKING ABOUT THIS FOR A COUPLE YEARS AT LEAST, HOW IT'S BEEN VERY MUCH INVOLVED OVER THERE I WAS A PROGRAM DIRECTOR WITHIN THE OFFICE, SHE'S INTERESTED IN PROVIDING RESOURCES, EDUCATIONAL RESOURCES FOR INVESTIGATORS TO HAVE EASY ACCESS TO AND SO THERE'S LOT OF THERE'S A LOT OF IDEAS IN MIND AND HOPEFULLY WE WILL ROLL OUT THESE EXPERIMENTS OVER THERE. THE TOPIC THAT CAME UP IS TO HAVE EASY ACCESS WEBINARS WHERE PEOPLE CAN COME UP WITH AN INTERESTING TOPIC THAT THEY WANT TO PURSUE AND GET A QUICK ACCESS TO A HALF AN HOUR EXPERTED OPINION OR HOW TO DO A CERTAIN THING. SO I BROUGHT UP OUR WEB SITE FOR THE OFFICE OF TRANSLATIONAL RESEARCH AND IT TURNS OUT WE NEED TO CREATE MORE TRAFFIC IN THIS WEB SITE AND MAKE THE INFORMATION MORE EASY AND ACCESSIBLE TO PEOPLE SO TAKEN--THEY THERE ARE BY THE TIME YOU IDENTIFY US AND THE GOING AND HE WILL PROGRAM ANNOUNCEMENT AND THAT--THAT REALLY RINGS TRUE TO ME BECAUSE I DIDN'T EXPERIMENT ABOUT TWO WEEKS AGO TO SEE HOW QUICKLY I CAN GO FROM A GOOGLE SEARCH TO A PROGRAM ANNOUNCEMENT AND IT WAS ABOUT SIX CLICKS THAT PERHAP SYSTEM GOOD FOR ME BUT NOT GOOD FOR A LOT OF PEOPLE. SO THOSE ARE SOME OF THE THINGS WE CAN IMPROVE ON AND LASTLY WHICH IS THE TOPIC FOR MANY OF US HERE IF NOT ALL OF US IS WHERE IS THE PRIORITY AND HOW IS THE DECISION MADE FOR ULTRA SMALL INDICATIONS AND WE'VE TALKED ABOUT HOW WE WOULD LIKE TO FUND PROJECTS AND SOME THAT ARE NOT READY FOR TRANSLATION AND SHOULD OF INFORMATION FOR THE GUIDELINES THE FDA PUBLISHED WOULD HELP TO AND THE FUNDING WE HAVE AVAILABLE, SO THESE ARE THINGS THAT WE WILL TAKE HOME WITH US AND HOPEFULLY WITH CAN TESTIMONY UP CAN PROGRAMS TO ADDRESS THESE THINGS. >> NOW [INDISCERNIBLE]. >> OKAY, WE HAD A NUMBER OF VERY GOOD DISCUSSIONS, I WILL START OUT WITH A COUPLE OF POINTS AND THEN CYNTHIA WAS MUCH MORE ORGANIZED. WE WILL GO ON, ONE THING THAT WAS REALLY A TAKE HOME FROM US WAS THE IDEA THAT THE ADVOCACY GROUPS NEED TO KNOW THEIR WORTH AND CLAIM THEIR SEAT AT THE TABLE, BOTH WHEN THEY MEET WITHIN NIH, WHEN THEY MEET WITH FDA AND KNOW THEY WERE BREEZING OF REAL VALUE TO THE TABLE. BESIDES THAT WE ALSO TALK ABOUT THE FACT THAT THEY HAVE TO UNDERSTAND THAT INDUSTRY ALSO NEEDS TO UNDERSTAND FOR THEIR BUSINESS MODEL, WHAT TYPE OF VALUE, IS GOING TO BE ATTRIBUTED TO WORKING WITH THAT ADVOCACY GROUP AND WHAT CAN IT BRING TO THEM. SO YOU HAVE TO PRESENT BOTH SIDES. THE FDA WAS FOCUS ON THE WITH US DURING OUR BREAK OUT SESSIONS BUT THE PEOPLE DID TALK ABOUT HARMONIZATION HERE IN THE UNITED STATES AND OUTSIDE THE UNITED STATES AND THE FACT THAT THE DIFFERENT REGIONS HAVE DIFFERENT REQUIREMENTS, AND WHAT THAT MEANT FOR DRUG DEVELOPMENT ESPECIALLY IN RARE DISEASES AND HOW FRUSTRATING THAT WAS. ANOTHER THING THAT WAS BROUGHT UP WAS THE IMPORTANCE OF KNOWLEDGE OF NATURAL HISTORY AND CYNTHIA SPOKE ABOUT THIS, SO I'M GOING TO TURN THAT PART OVER TO HER WHEN SHE TALKED ABOUT FLUCTUATIONS IN AT AND BEING ABLE TO MEASURE AT DIFFERENT TIMES IN THE DISEASE WHAT YOU WOULD STUDY WOULD VALID AND RELIABLE SCHETHAT'S SOMETHING THAT INDUSTRY MAY NOT REALIZE IMMEDIATELY BUT IT'S SOMETHING THAT THE PARENTS AND PATIENTS WOULD BE ABLE TO COMMUNICATE EASILY TO AN INDUSTRY PARTNER. AND BE ABLE TO SORT OF GUIDE THAT CLINICAL DEVELOPMENT PROGRAM. >> [INDISCERNIBLE]. >> WE'RE ALWAYS FORGETTING THE MICROPHONE, TOO, BUT YOU KNOW WE WERE JOKING THAT FOR THREES THREE DIFFERENT SESSIONS, THE ONE ON BASIC RESEARCH TRANSLATIONAL RESEARCH AND CLINICAL SITES WE COULD HAVE ALL LINED UP AND THE AT SAT THE TABLE BECAUSE IT IS A CONTINUING ONE FEEDS OFF THE AND OTHER SO NATURAL HISTORY IS ONE OF THOSE REOCCURRING TOPICS BECAUSE THE BETTER YOU UNDERSTAND THE DISEASE, THE MORE YOU CAN INFORM CLINICAL TRIAL DESIGN, THE BETTER DESIGN YOUR CLINICAL TRIAL, THE MORE RIGOROUS AND ROBUST YOUR OUTCOME AND HOW MUCH YOU CAN DEPEND ON THE DAT THAT YOU OBTAIN FROM THE TRIAL. SO THE EXAMPLE I GAVE FOR A-T, IS THAT WHEN A CHILD IS BORN WITH ATAXIA THEY SEEM FINE AND THEN WHEN THEY STAND UP THEY WOBBLE AND IT'S A WOBBLE YOU NEVER RECOVER FROM THAT AND THEN CHILDREN OFTEN HAVE A STATIC PHASE, THEY DON'T DEGENERATE SO UNTIL THEY'RE SIX, YOU GET A MISDIAGNOSIS OF CEREBRAL PALSY OR SOMETHING LIKE THAT, AND THEY UNDER GO RAPID DECLINE, NEUROLOGICAL ABILITIES AND BY THE AGE OF 10, THEY'RE WHEELCHAIR BOUND AND IN ANOTHER FEW YEARS THEY REACH A PLATEAU WHERE A LOT OF THE NEUROLOGICAL SYMPTOMS JUST KIND OF PLATEAU OUT, LEVEL OUT BUT THEN YOU GO SOME HYPER KINETIC MOVEMENT, ET CETERA THAT RAISE THEIR RUGLY HEAD AT THAT TIME BUT WHAT YOU'RE TRYING TO TARGET WHAT YOUR GOAL IS WITH THE THERAPEUTIC YOU NEED TO KNOW YOUR PATIENT IS, AND THIS IS JUST AN EXAMPLE OF KNOW YOUR PATIENT POPULATION, KNOW THE GOAL OF YOUR CLINICAL DRILL AND HOW TO CHOOSE YOUR PATIENTS WISELY. SO THERE WERE OTHER TOPICS THAT WE--GANNA, WE MIGHT NOT HAVE THE ANSWERS BUT WE TOOK A DEEPER DIVE OR DISCUSSED A BIT MORE, I'M NOT QUITE THAT ORGANIZED BUT WE DELVED A LITTLE BIT INTO RECRUITMENT ISSUES. RECRUITMENT ISSUES REVOLVING AROUND MAYBE DISEASES THAT HAVE A HIGHER REFULENCE LIKE PARKINSON'S DISEASE IF YOU HAVE MULTIPLE TRIALS GOING ON AT A TIME, ISSUES THERE, VERSES RECRUITLET ISSUE FIST YOU ARE DEALING WITH A MORE RARE DISEASE WHERE YOU HAVE LIMITED POPULATIONS AND PROBABLY FEWER TRIALS. WE ALSO HAD A DISCUSSION ABOUT THE HELPFULNESS OR NOT OF CLINICALTRIALS.GOV AND I ACTUALLY FIND THAT EASIER TO SEARCH THAN I DO REPORTER, BUT I ALWAYS HAVE TO RESET MY QUERY FOR REPORTER BUT YOU KNOW CLINICAL TRIALS.GOV ITSELF BE IMPROVED? SIMPLER LANGUAGE, EASIER TO SEARCH SO THAT IT BETTER SERVES THE INTEREST OF ADVOCATES AS WELL AS INDUSTRY AND DID A SEARCH. SO THEN WE HAD A DISCUSSION ABOUT IF YOU START A RELATIONSHIP WITH MAYBE A SMALL BIOTECH AND THEN THAT BIOTECH BECOMES ABSORBED BY A LARGER PHARMA, HOW DO YOU--HOW DOES YOUR RELATIONSHIP TRANSITION AS THE BIOTECH IS TRANSITIONED INTO THE LARGER PHARMA AND HOW DO YOU MAINTAIN THAT RELATIONSHIP. THAT WAS JUST A TOPIC OF DISCUSSION, SOMETHING THAT WAS BROUGHT UP TO THINK ABOUT. SO THAT, YOU KNOW YOUR PROGRAM DOESN'T FALL THROUGH THE CRACKS OF THAT TRANSITION. ANOTHER TOPIC WAS THE IMPORTANCE OF CLINICAL TRIAL NETWORKS, PLACE, SITES CAN YOU HAVE CLINICAL TRIALS, SO WE DISCUSSED DIFFERENT MODELS THAT ARE OUT THERE, VARIOUS SUCCESSFUL MODEL IS THE FEATURED ATAXIA RESEARCH ALLIANCE, COLLABORATING WITH MDA, THEY HAVE A VERY NICE CLINICAL RESEARCH NETWORK. AND THEN FOR OTHERS LIKE THE A-T CHILDREN'S PROJECT WE SOLELY FUND OUR A-T CLINICAL CENTER AT JOHNS HOPKINS HOSPITAL AND OF COURSE THERE'S MODELS THAT HAVE BEEN PUT IN PLACE BY THE NIH OFFICE OF RARE DISEASE RESEARCH, NOW PART OF NCATS BUT IT IS THEIR RARE DISEASE RESEARCH CONSORTIUM. AGAIN, YOU PROBABLY AS A SINGLE DISEASE COULDN'T JUST GET MONEY FUNDED FOR YOUR DISEASE OR A TRIAL OR NATURAL HISTORY STUDY FOR YOUR DISEASE THROUGH THESE CONSORTIA BECAUSE AS THE NAME SUGGESTS YOU NEED TO PAIR UP WITH OTHER SIMILAR DISEASES IN ORDER TO OBTAIN THAT FUNDING. AND LIKE, YOU KNOW, FUNDING COMES FROM THE NIH, IT'S THERE FOR A LIMITED PERIOD OF TIME AND YOU COMPETE FOR RESILIENCE NEWAL AND SO YOU HAVE TO THINK ABOUT, IF YOU GET A RESILIENCE NEWAL, THAT'S GREAT, IF YOU DON'T HAVE DATA AND THINGS OF THAT NATURE. LET'S SEE, I THINK THE LAST THING, IT WAS INTERESTING SOMEONE BROUGHT UP PARTNERING NOT WITH PHARMA BUT WITH DEVICE COMPANIES OR COMPANIES THAT DEAL--TECH COMPANIES LIKE MICROSOFT WAS AN EXAMPLE AND THAT A NICE WAY TO GARNER THEIR ATTENTION IS WITH A PRIZE PARADIGM AND I DON'T KNOW IF ELIZABETH WANTED TO TALK MORE, TY'RE TECHY TYPES BECAUSE THEY LOVE A GOOD PROBLEM THEY CAN SOLVE. AND YOU DON'T ARE TO SPEND RELATIVELY SPEAKING IN ORDINANT AMOUNT OF MONEY ON THE PRIZE, PRIZE MONEY, 25,000, 50,000, BUT THEN, ONCE YOUR PROBLEM IS ADDRESSED THEN YOU HAVE TO CARRY THAT INITIAL ANSWER THAT THEY GOT, AND THEN HOW DO YOU CONTRARY THAT FORWARD AND THEN WHEN YOU GUARD THE INTEREST OF THESE TECHNOLOGY COMPANIES AND THESE ENGINEERING COMPANIES, YOU KNOW HOW DO YOU NOT GET LOST IN THEIR CRACKS WITH THEIR INTEREST, YOU KNOW. >> ONE THING THAT ALSO SORT OF BUILDS ON THAT IS THE IDEA OF FINDING A WAY TO LET THE A-T COMMUNITY BENEFIT FROM LESSONS LEARNED BECAUSE A LOT OF PEOPLE HAVE DEALT WITH DIFFERENT ASPECTS OF INDUSTRY, SMALL MOM KIEWLS AS WELL AS DEVICES AND THE QUESTIN IS HOW DO YOU LEARN FROM WHAT OTHER PEOPLE HAVE GONE THROUGH AND TAKE THAT FOLLOW UP AND THERE ISN'T A GOOD FORUM FOR THAT, THAT WOULD BE SAYING THAT WOULD BE VERY NICE. >> THANKS VERY MUCH. [ APPLAUSE ] >> OH AND I JUST WANTED TO MAKE ONE ANNOUNCEMENT FOR A MOMENT, IF THERE'S ANYBODY FROM THE NONPROFIT WORLD WHO'S INTERESTED IN JOINING THE NINDS, NONPROFIT ORGANIZATION COMMUNITY, PLEASE VOLUNTEER AND THEN COMMUNICATE WITH MARY OR MARGO WARREN IF YOU'RE INTERESTED IN JOINING. [INDISCERNIBLE]. >> RIGHT. >> REALLY APPRECIATE THE COMMITTEE THIS YEAR, THEY DID A GREAT JOB AND AGAIN IT'S GOING TO BE HARD TO BEAT NEXT YEAR BUT WE'RE GOING TO DO IT SOMEHOW AND WE CERTAINLY LEARNED A TREMENDOUS AMOUNT FROM LISTENING TO YOU TODAY AND WE TOOK NOTES AND I THINK, YOU KNOW WE LIKE TO COME OUT WITH AN ACTION PLAN AFTERWARDS. AND SO WE WILL BE FLOATING SOME IDEAS BY YOU AS WE GO FORWARD. AND FOR THE PEOPLE WHO COME TO COUNCIL TOMORROW, PLEASE, PLEASE TAKE ADVANTAGE OF THAT, THE FACT THAT THIS MEETING IS RIGHT IN FRONT OF THE COUNCIL IS PURPOSEFUL SO PEOPLE COULD COME TO THE OPEN SESSION. AND LARRY TABAK THE DEPUTY DIRECTOR OF NIH WILL ALSO BE SPEAKING. WE HAVE A COUPLE OF TOPICSOT TABLE FOR THE OPEN COUNCIL. I GIVE A REPORT BASICALLY ON WHAT WE'RE DOING, I GIVE A REPORT ON WHAT WE'VE SPENT OVER THE YEARS SO YOU GET A SENSE OF WHERE ALL THE MONEY WENT AND THEN THERE WILL BE DISCUSSIONS ABOUT OUR PLANS FOR FUNDING NEW INVESTIGATORS, THEY'LL BE DISCUSSIONS OF THE BRAIN INITIATIVE TOMORROW IN THE OPEN SESSION, AND ALSO DISCUSS ON OUR CURRENT POLICY WITH REGARDING AWARDS, WE GIVE AWARDS TO A VERY SELECT FEW INVESTIGATORS CALLED THE JAVITZ AWARD, WHICH IS A PRESTIGIOUS AWARD, WE WILL DISCUSS POLICY AS WE GO THERE. SO THOSE ARE THINGS THAT ARE ON TOP FOR THE OCHE SESSION TOMORROW. OH YES, ONE COMMENT? >> [INDISCERNIBLE]. . >> ABSOLUTELY. >> [INDISCERNIBLE]. >> GREAT. >> EVALUATION FORMS ARE IN THE PACKET AND DROP THEM ON THE DESK BEFORE WE LEAVE, ANYTHING ELSE MARRIAN? >> [INDISCERNIBLE]. >> OH I FORGOT ABOUT THE STRATEGIC PLAN! [LAUGHTER] >> YOU'RE RIGHT. >> YEAH, SO THE STRATEGIC PLAN WE WILL TALK ABOUT TOMORROW, PAUL WHY DON'T YOU COME UP AND JUST BRIEFLY--THE THINGS THAT CAME OUT OF THE BREAK OUTS. >> I DID THE OLD FASHION THING ON A BOARD ON THE SHEET SO I WILL HAVE THIS HERE AS A CHEAT SHEET, OVER HERE, SO WE JUST STARTED BY BY GOING BACK OVER AND TALKED ABOUT THE IN THE LARGER SESSION IN TERMS OF GENERAL THEMES BUT CUT TO THE CHASE, I THINK THE BIG THING THAT CAME OUT OF OUR DISCUSSION WAS THAT THE WHOLE ISSUE OF AN EMPHASIS IN THE PLAN ON BETTER COLLABORATIONS ACROSS THE INSTITUTE, AND ALSO ESPECIALLY BETWEEN THE NIH AND THE OUTSIDE NG Os WAS REALLY THE BIG THING THAT CAME FORWARD. AND SO, YOU KNOW, THAT SHOULD BE A REAL POINT OF EMPHASIS IN THE PLAN AND NIH SHOULD THINK HARD ABOUT HOW BEST TO DO THAT. SOME EXAMPLES WERE GIVEN OF A GROUP OF NG Os WHO WANT TO WORK ON A COMMON PROBLEM, HOW DO THEY COME TO NIH AND IDENTIFY THE NICs THAT ALL WORK TOGETHER AND IT'S A BIT MORE COMPLICATED THAN JUST ONE NGA COMING TO ONE INSTITUTE, WE TALK ABOUT THE DIFFICULTIES ESPECIALLY FOR SOME NEW--NEW GROUPS GETTING TOGETHER AND COMING TO NIH AND NOT REALLY KNOWING WHAT RESEARCH IS AVAILABLE OR HOW TO GO ABOUT DOING IT OR MORE OF AN EFFORT MADE ON THE NIH WEB SITE TO DO THAT, WE TALKED ABOUT THIS DOWN HERE AS OFFICE OF PATIENT OF ADVOCACY AND OFFICE IN THE BUILDING CALL TED THE OFFICE OF OUTREACH AND POLICY HEADED BY JANET LAMBERT WHO WAS HERE YESTERDAY. IT'S A NEW OFFICE, WE'RE NOT SURE, EVERYTHING AT THE OFFICE DOES BUT IT SEEMED LIKE THAT MIGHT BE A NATURAL FOCUS MAYBE FOR REACHING OUT TO THE NG OASKS PROVIDING RESOURCES. OTHER THINGS WE TALKED ABOUT THE PCORI, FUNDING GOES TO 2018 AND NIH THINK ABOUT WHAT SHOULD HAPPEN IF PCORI DIDN'T GET RENEWED SINCE IT'S WITHIN THE TIME PERIOD OF THE NIH STRATEGIC PLAN, IT MIGHT WANT TO THINK ABOUT WHAT IT WILL WANT TO DO SO MAKE SURE THAT THAT EFFORT AND PROGRESSION MADE BY PCORI, DOESN'T EVALUATE. STEWARDSHIP, WE TALKED ABOUT TRAINING, NOT JUST THE TOPIC CAME UP NOT JUST TYPICAL TRAINING OF THE NEXT GENERATION SCIENTISTS BUT GIVEN ALL THE CHANGES THAT HAPPEN INDEED PHARMACEUTICAL INDUSTRY AND A LOT OF AREAS NOT PUTTING IN AS MUCH EMPHASIZE ON DRUG DEVELOPMENT ANYMORE, YOU KNOW THE NEXT GENERATION OF PEOPLE WHO KNOW HOW TO DO DRUG DEVELOPMENT SHOULD THERE BE THOUGHT GIVEN TO TAKEN--THEY TYPE OF TRAINING. THERE'S TALK ABOUT THE PLAN THAT INSPIRATION AND ASPIRATIONAL AND COULD BE A GREAT SELLING POINT TO CONGRESS IN TERMS OF PROVIDING MORE FUNDING FROM NIH AND I'M JUST CHANNELS WHAT THE NG O TOLD ME. AND AS WELL AS BEING ARGUMENT FOR MAINTAINING AND ENHANCING OUR U.S. COMPETITIVENESS WORLD WIDE AND THEN LASTLY THERE WAS TALK ABOUT THE NEED FOR BETTER PORTFOLIO AAINAL SIS TOOLS SO WAIT FOR NIH TO LACK AT PORTFOLIO AND SEE WHAT WE'RE DOING AND WHERE THERE MIGHT BE GAPS AND AGAIN THIS WOULD BE A NATURAL OPPORTUNITY FOR PARTNERSHIPS WITH THE OUTSIDE WORLD TO SEE WHAT OTHER GROUPS ARE DOING, INDUSTRY AND NG Os IN TERMS OF LOOKING AT AN AREA, WHAT ARE THE GAPS HOW CAN WE BETTER WORK TOGETHER AND HOW NIH IS STARTING TO MAKE MORE BEST AND MORE SOPHISTICATED ANALYSIS TOOLS SO NOT JUST A LIST OF GRANTS OF WHAT'S GOING ON IN THE AREA BUT SOME ATTEMPT AT VISUALIZATION, TOOLS TO ACTUALLY LOOK AT WHAT'S GOING ON. SO WE WILL--WE'VE SUMMARIZED THESE AND WE WILL BE SENDING THESE OVER TO DR. TABAK'S OFFICE AND IF YOU'RE HERE TOMORROW, I D'T KNOW HOW MUCH TIME WE'LL HAVE FOR QUESTIONS BUT MAYBE SOME OF THIS STUFF WILL COME UP TOMORROW. >> GREAT. >> GREAT. >> THANK YOU VERY MUCH. >> [ APPLAUSE ] >> I THINK WE'RE DONE. SO THANKS, EVERYONE. ALL RIGHT.