WELCOME TO THE 31st MEETING OF THE NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES. AND I THINK -- I WANT TO WELCOME YOU TO THE MEETING TODAY. THANK YOU FOR YOUR PARTICIPATION IN THIS ACTIVITY, IT'S IMPORTANT FOR THE WORK WE DO. AND NOW I'D LIKE TO TURN IT BACK OVER TO ANNA TO GET STARTED WITH THE PROCEEDINGS. ANNA, BACK TO YOU. >> THANK YOU, JONI. ALL RIGHT. I'D LIKE TO START WITH OUR ROLL CALL, TED HOLEMAN. >> PRESENT. >> ANNIE KENNEDY. >> HERE. >> KRESLER. >> HERE. >> ANDREW LOWE. >> HERE. >> McVEERY. >> PRESENT. >> KEITH MILLER. >> HERE. >> RAJESH. >> PRESENT. >> AND PAULA. >> HOWDY. >> MEMBERS NOT PRESENT TODAY AT THE MOMENT ARE PAUL HARRIS AND REBECCA JACKSON. I'D LIKE TO REVIEW OUR AGENDA. FIRST OUR DIRECTOR WILL PRESENT THE DIRECTOR'S REPORT. NEXT WE'LL HAVE PROGRAM UPTAKE FROM DIVISION OF CLINICAL INNOVATION. AND THEN WE'LL HAVE OUR CONCEPT CLEARANCE SESSION AFTER A BREAK. FOR ANNOUNCEMENTS, EVERYONE IN A ZOOM MEETING IS A PANELIST TODAY SO YOU'RE FREE TO SPEAK. HOWEVER, IN ORDER TO MAINTAIN A SMOOTH FLOW TO THE PRESENTATIONS WE REQUEST YOU USE THE "RAISE HAND" FEATURE AND WAIT UNTIL CALLED UPON TO PROVIDE INPUT. PLEASE ALLOW THE SPEAKERS TO MOVE THROUGH THEIR PRESENTATIONS NOTING COMMENTS, PRESENTING THEM WHEN CALLED UPON. WE'RE USING THE VIDEOCAST FEATURE TODAY. SO AUDIENCE MEMBERS MAY SUBMIT COMMENTS BY USING THE E-MAIL FUNCTION AVAILABLE ON THE NIH VIDEOCAST SITE, USING THAT SEND LIVE FEEDBACK BUTTON OR SENDING E-MAIL TO N CATSCOUNCILINPUT@NI. ANYTHING IN THE CHAT WILL BE INCORPORATED INTO THE MINUTES SO KEEP USE OF CHAT TO A MINIMUM. MAKE SURE WHEN YOU'RE SPEAKING YOUR CAMERA IS ON, SO YOU ARE SPOTLIGHTED FOR VIEWERS OF THE VIDEOCAST. IF YOU'RE NOT ON CAMERA THE PREVIOUS SPEAKER REMAINS SPOTLIGHTED. THE FUTURE DATES ARE IN 2023, JANUARY 26-27, MAY 25, SEPTEMBER 28, IN 2024 THE DATES ARE JANUARY 18 AND 19, MAY 23, SEPTEMBER 26. YOU'LL NOTE THE JANUARY MEETINGS ARE OVER TWO DAYS AND THEY ARE VIRTUAL. NEXT SLIDE PLEASE. WE'RE SEEK APPROVAL OF MINUTES FROM MAY 2022, AVAILABLE IN THE ELECTRONIC COUNCIL BOOK PROVIDED FOR YOUR REVIEW. COULD WE HAVE A MOTION TO APPROVE THE MAY 2022 MEETING MINUTES? >> SO MOVED. >> SECOND? >> SECOND. >> ALL IN FAVOR? >> AYE. >> ANY OPPOSED? ANY ABSTENTIONS? THE MINUTES ARE APPROVED. I'D LIKE TO TURN IT OVER TO JONI FOR THE DIRECTOR'S REPORT. JONI? >> ALL RIGHT. THANK YOU SO MUCH, ANNA. AND WELCOME AGAIN. IT FEELS LIKE IT'S BEEN, GOSH, FEELS LIKE IT'S BEEN OVER A YEAR SINCE WE'VE MET. IT HASN'T, BUT THE MONTHS INTERVENING HAVE BEEN PACKED. AND THERE'S A LOT TO TALK ABOUT. I'M GOING TO JUMP RIGHT IN. I KNOW WE'VE ALL HAD A BUSY SUMMER BUT I WANT TO GIVE A SENSE OF WHAT'S BEEN HAPPENING ON OUR SIDE OF THINGS. THERE HAVE BEEN A LOT OF CHANGES. I'LL GO THROUGH STAFF CHANGES. FIRST OFF I WANT TO MENTION, NEXT SLIDE, WE HAVE A NEW MEMBER ON THE NCATS ACCELERATION REVIEW BOARD, WITH LISA SHILL, PATIENT ADVOCACY CONSULTANT FROM J AND L PARTNERS AND WE'RE EXCITED TO HAVE HER VOICE JOIN US. WE'RE STARTING TO BUILD OUR CADRE OF MEMBERS, AND I HOPE WE PULL TOGETHER TO BRING THIS GROUP TOGETHER, EXCITED FOR LISA TO JOIN US. NEXT SLIDE. A COUPLE STAFF RETIRING, I WANT TO GIVE A SENSE OF THOSE CHANGES, RANDY REDMON HAS WORKED BEHIND THE SCENES AS DEPUTY EXECUTIVE OFFICER WITH KEITH, WHO IS OUR EXECUTIVE OFFICER. RANDY HAS BEEN WITH THE NIH 38 YEARS, JUST BEEN REALLY INCREDIBLE, STEADFAST, AND HELPING NCATS GET SET UP AND MOVING PROCESS FORWARD, NOT ALWAYS THE USUAL PROCESSES. HE'S DONE A TERRIFIC JOB MAKING SURING WE HAVE A GOOD FOOTING MOVING FORWARD AND I'M EXCITED TO TELL YOU ABOUT BEKAH GEIIGER, JOINING US AS NEW DEPUTY E.O. DR. CAROL LAMBERT IS RETIRING AFTER 20 YEARS OF SERVICE. SHE'S BEEN THE CHIEF SCIENTIFIC REVIEW BRANCH IN DEA FOR -- SINCE NCATS REALLY BEGAN. SHE HAS BEEN INSTRUMENTAL IN HELPING NCATS THROUGH PRIZE COMPETITIONS AND INTRAMURAL ACTIVITIES, SO REALLY THINKING OUTSIDE OF THE BOX FOR OUR REVIEW OFFICE. AND SHE'S ALSO MORE RECENTLY BEEN JUST KEY BEHIND HOW WE PULLED TOGETHER THE NCATS EMERGENCY FOA REVIEW PROCESSES AND TEMPLATES. WE'LL MISS CAROL BUT WISH HER THE BEST AND WE'RE UNDERGOING A SEARCH FOR THE CHIEF OF THAT BRANCH FOR NCATS. NEXT SLIDE PLEASE. AND DON LO IS LEAVING NCATS, NOT RETIRING, HE'S JOINING SISTER ORGANIZATION AT THE EUROPEAN INFRASTRUCTURE FOR MEDICINE, IN THE NETHERLANDS, HE WILL BE STANDING UP VERY SIMILAR KINDS OF PROGRAMS LIKE WHAT NCATS DOES, TO ADVANCE AND ACCELERATE REPURPOSING OF APPROVED DRUGS FOR RARE DISEASES AND REPRESENTING REALLY THAT EXCITING EFFORT FROM THE EUROPEAN UNION AND BUILDING ON LESSONS LEARNED, I HOPE, FROM NCATS AS WELL. AND SO HERE HE HAS SPEARHEADED TRANSFORMATIONAL WORK THROUGH THE THERAPEUTICS DEVELOPMENT BRANCH, LEFT A STRONG ORGANIZATIONAL STRUCTURE AND VARIETY OF PROCESS IN PLACE AND THERE ARE LOTS OF MILESTONES HE'S BEEN ABLE TO COVER UNDER HIS LEADERSHIP, INCLUDING SEVERAL DOZEN INDs, START-UP OF OUR TRANSFORMATIONAL EFFORT THERAPIES, AND THE FIRST TWO FDA-APPROVED DRUG CANDIDATES SUPPORTED BY THE TRANSLATIONAL DEVELOPMENT BRANCH. SO WE'RE EXTREMELY GRATEFUL FOR DON'S CONTRIBUTIONS TO NCATS, STEERING TDB SO ABLY FOR THESE PAST FEW YEARS, AND WE WISH HIM THE BEST AT EATRIS. WHAT EXCITES ME ABOUT THIS CHANGE IS THAT WE NOW HAVE A STRONG PARTNER AT EATRIS AND I HOPE WE CAN FORGE MORE COLLABORATIONS GLOBALLY. CONGRATULATIONS TO DON. AND I THINK IN THE MEANTIME, YOU SAW AND HEARD LIZ OTTINGER SPEAK AT LAST COUNCIL, I'M SUPER EXCITED SHE'S AGREED TO SERVE AS ACTING DIRECTOR IN THE INTERIM WHILE WE DO A SEARCH FOR THIS POSITION. THANKS TO LIZ FOR STEPPING IN AND ABLY TAKING ON THIS ROLE AS WE MOVE FORWARD. SO NEXT SLIDE. IN OTHER AREAS OF NIH LEADERSHIP SEARCHES, THERE'S STILL NO, AS YOU HEARD, STILL NO NIH DIRECTOR TO RELAY. BUT DR. LARRY TABAK IS CONTINUING TO PERFORM THE DUTIES OF THE NIH DIRECTOR AND PUSH THINGS FORWARD. AND I HOPE TO HAVE MORE NEWS ON THIS AT OUR NEXT COUNCIL MEETING. THERE HAVE BEEN OTHER MOVEMENTS THOUGH. I'LL LIST ONE HERE AND A FEW OTHER SLIDES. BUT PRESIDENT BIDEN HAS SELECTED DR. MONICA BERTAGNOLLI AS THE FIRST WOMAN TO DIRECT NCI AND SO SHE WILL START HER TENURE THIS FALL. AS YOU PROBABLY HEARD TONY FAUCI WILL BE STEPPING DOWN AT THE END OF THIS YEAR, WE HAVE A VACANCY AT NIAID, AND THERE WILL BE ANOTHER LEADERSHIP SEARCH THAT WILL BE UNDERWAY STARTING RELATIVELY SOON. AND NO NEWS TO REPORT FOR THE DIRECTOR OF NCATS. I'M CONTINUING TO SERVE AS ACTING DIRECTOR AND VERY HONORED TO DO SO. BUT, AGAIN, HOPEFULLY WE'LL HAVE SOME NEW UPDATES FOR YOU AT OUR NEXT COUNCIL MEETING. NEXT SLIDE PLEASE. THERE HAVE BEEN OTHER MOVEMENTS, YOU'VE ALSO HEARD PROBABLY RECENTLY IN THE LAST TEN DAYS OR SO THAT PRESIDENT BIDEN ANNOUNCED HIS INTENT TO APPOINT DR. RENEE WEGERSAN, OUR INAUGURAL DIRECTOR OF THE ADVANCED RESEARCH PROJECTS AGENCY FOR HEALTH, EXCITED TO HEAR MORE ABOUT HER AT ARPA-H, I LOOK FORWARD TO SEEING HER IN THE NEW ROLE. NEXT SLIDE. WE'VE HAD DR. ADAM RUSSELL JOIN US AS THE ACTING DEPUTY DIRECTOR OF ARPA-H, AND INTENT HERE FOR WHAT HE'S BEEN DOING PRIMARILY IS TO GET A LAY OF THE LAND OF WHAT NIH DOES, HOW WE SET UP PROCESSES FOR BRINGING IN GRANTS, SUPPORT THEM. SO THINKING ABOUT WHAT SYSTEMS ARE NEEDED, HOW CAN WE ALIGN THOSE SYSTEMS WITH SOMETHING THAT'S ALREADY BUILT RATHER THAN STARTING FROM SCRATCH. HE'S BEEN SORT OF DOING THE WIRING AND PLUMBING AND SETTING THE STAGE, AND THEN NOW THAT WE HAVE THE APPOINTMENT OF DR. WEGRZYN THEY WILL FIGURE OUT THE SCIENTIFIC NEXT STEPS OF WHAT ARPA-H WILL LOOK LIKE. EXCITING TIMES FOR THAT NEW AGENCY AS WE MOVE FORWARD. NEXT SLIDE PLEASE. I'LL TRANSITION INTO NEWS AND ANNOUNCEMENTS HERE. AND JUST GIVE YOU A SENSE OF OTHER THINGS THAT ARE GOING ON. NEXT SLIDE. WE'VE BEEN DOING A LARGE PUSH, I DON'T KNOW IF IT'S LARGE BUT WE'VE BEEN STEADILY KIND OF PUSHING OUT DIFFERENT MESSAGES THROUGH THE NCATS DIRECTOR'S CORNER AND WORKING CLOSELY WITH EMILY MARTY AND COMMUNICATIONS TEAM WHO HAVE DONE A SPECTACULAR JOB GETTING THESE MESSAGES OUT. IF YOU HAVEN'T SEEN THE DIRECTOR'S CORNER, I ENCOURAGE YOU TO TAKE A LOOK, READ MY LATEST FULL MESSAGE, WHICH IS ON HOW NCATS WORKS TO ADVANCE THE MISSION WITH STAKEHOLDERS, AND A THEME THAT SAYS MANY HANDS MAKE LIFE WORK. IT'S A TRUE THING. WE'RE EXCITED TO BRING ON AND MEET NEW STAKEHOLDERS AND PUSH FORWARD ON AUDACIOUS GOALS WE'VE ESTABLISHED. WE HAVE A SERIES OF MESSAGES ON THOSE BOLD GOALS, NCATS BOLD GOAL SERIES CIRCLED IN RED. WE HAVE ABILITY TO SIGN UP FOR NCATS LISTSERV, IF YOU HAVEN'T DONE THAT I HOPE YOU DO SO AND YOU'LL GET ALL THE LATEST MESSAGES IN YOUR IN-BOX. SO THAT'S WHERE WE ARE WITH THE DIRECTOR'S CORNER, AGAIN TRYING TO GET MORE MESSAGES OUT ABOUT HOW WE'RE TRYING TO GET OUR VISION ABOUT BRINGING MORE TREATMENTS TO ALL PEOPLE, MORE QUICKLY, OUT THERE AND ENGAGING WITH THE COMMUNITY IN THAT WAY. IT'S NOT MEANT TO BE A ONE-WAY COMMUNICATION. IT'S MEANT TO BE BIDIRECTIONAL, THERE'S ALWAYS A WAY TO SEND FEEDBACK BACK, BUT WE'D LIKE TO FIGURE OUT WAYS COMMUNICATING BIDIRECTIONALLY, WORKING ON A VARIETY OF ENGAGEMENTS THROUGH TEA TIME, ROUNDTABLE DISCUSSIONS, THINGS OF THAT NATURE. WE'LL DO THOSE AS WE MOVE FORWARD. NEXT SLIDE PLEASE. SO ONTO THE BUDGET, WHERE ARE WE WITH THE FY 23 BUDGET PROCESS? WE HAVE 8 DAYS LEFT IN THIS MONTH, THAT MEANS 8 DAYS LEFT IN THIS FISCAL YEAR. WE'RE GETTING RIGHT DOWN TO THE WIRE. AND SO I THINK IT'S A FAIRLY SAFE BET TO SAY WE'RE EXPECTING A CONTINUING RESOLUTION TO SUPPORT US AS WE CROSS THE FISCAL YEAR BOUNDARY HERE IN OCTOBER. AND WE DON'T HAVE MUCH NEWS ON THIS YET BUT PLEASE STAY TUNED. UNTIL THEN, FROM THE HOUSE SIDE, THE HOUSE APPROVED THEIR APPROPRIATIONS THROUGH THEIR APPROPRIATIONS COMMITTEE ON JULY 5, THEIR HOUSE BUDGET, AND FROM THIS PERSPECTIVE YOU SEE OVERALL INSTITUTE AND CENTER INCREASE THAT AVERAGES 3.2% ACROSS THE BOARD FOR THE INSTITUTES AND CENTERS, AND FROM THE SENATE SIDE THEIR DRAFT BILL WAS RELEASED JULY 28, AND THEY HAVE AN OVERALL INCREASE OF 3.1%, CLOSE IN THAT REGARD, NCATS SPECIFIC ASPECTS, THERE ARE NUANCES TO BRING TO LIGHT. WE OF COURSE VERY MUCH APPRECIATE INCREASES IN CTSA BUDGET LINE ITEM, CALLED OUT SPECIFICALLY HERE UNDER THE NCATS TOTAL WITH CTSA LINE ITEM AND NON-CTSA BUDGET. THE INCREASES TO THE CTSA ARE CONSISTENT WITH OVERALL INSTITUTE AND CENTER INCREASES OF 3.2% ON THE HOUSE SIDE, 3.1% ON SENATE SIDE. WE'RE CONCERNED ABOUT LACK OF GROWTH OR SMALLER GROWTH IN NON-CTSA LINE. IT'S NOT IN LINE WITH OVERALL I.C. INCREASES, AND SOME OF THIS MAY MEAN THAT DEPENDING ON HOW THINGS GO IN TERMS OF THE CONFERENCE FOR THE HOUSE AND SENATE TO GET TOGETHER FOR THE FINAL BILL, WE WANT TO SEE HOW THAT TURNS OUT OF COURSE, BUT IF IT'S FAIRLY FLAT, THAT MAY MEAN THAT WE DELAY OR SLOW DOWN SOME OF THE RECENT CONCEPT CLEARANCES THAT HAVE BEEN REVIEWED BY COUNSEL, AND/OR PERHAPS CUT OTHER AREAS OF PLANNED GROWTH. BUT WE'RE OBVIOUSLY VERY GRATEFUL FOR THE SUPPORT WE RECEIVE AND WE WILL DEFINITELY MAKE THE BEST USE OF WHATEVER BUDGET WE RECEIVE FOR THAT MATTER. SO I THINK WE'VE DONE THAT VERY WELL IN THE PAST, WE'LL CONTINUE TO DO THAT AS WELL. HOW AND SENATE GO TO CONFERENCE TO COME UP WITH FINAL NUMBERS, A CONTINUING RESOLUTION UNTIL THEN. WE'RE WORKING WITH OUR CHANNELS WITHIN NIH TO COMMUNICATE SORT OF THESE IMPACTS THAT WE MIGHT BE SEEING IF THESE HOLD UP, BUT HOPEFULLY THEY WENT AND I'M OPTIMISTIC THAT WILL BE THE CASE. STAY TUNED. I WANTED TO RELAY A FEW AWARDS FOR SOME NCATS STAFF WHO REALLY DESERVE THESE ACCOLADES. THIS IS AN HHS DEPARTMENTAL AWARD, RECOGNIZING LEVEL OF THE SECRETARY, SECOND'S AWARD FOR DISTINGUISHED SERVICE. THIS PARTICULARLY IS ON THE RAPID ACCELERATION OF DIAGNOSTICS INITIATIVE, RADx, RUN OUT OF THE NIBIB I.C., THEY HAVE DONE A FANTASTIC JOB AT NIBIB RUNNING THIS PROGRAM. I THINK IT REALLY HAS A FUTURE FOR CONTINUING BEYOND COVID. BUT IN ADDITION TO THE WORK WE'VE DONE HERE AT NCATS THERE'S BEEN A TEAM AT NIBIB AS WELL. A QUICK SHOUT OUT TO STAFF WHO CONTRIBUTED TO THAT. AND RELAY THAT TO YOU. THE OTHER WORTHY NOTE HERE IS THAT BERNIE RETIRED EARLY WITH 50 YEARS OF SERVICE TO THE NIH, A DELIGHT TO WORK WITH, FOUNDATIONAL TO NCATS, I THANK HIM FOR HIS DEDICATED SERVICE FOR NCATS AND NIH WRIT LARGE. NEXT SLIDE PLEASE. ONE ANNOUNCEMENT TO MAKE IS THAT WE'RE UNDERGOING A PRETTY DEEP MODERNIZATION OF OUR GUARD WEBSITE, THE GENETIC AND REAR DISEASE INFORMATION CENTER, ONE OF THE TOP TEN WEB SIDES USED BY THE PUBLIC. PATIENTS, CLINICIANS, STAKEHOLDERS, FREQUENTLY TRAVELED WEBSITE. UNFORTUNATELY MODERNIZATION IS NEEDED TO KEEP UP, BUT I WANTED TO RAISE AWARENESS. WE'RE HOPING THAT WE WILL CONTINUE TO MOVE FORWARD IN THIS MODERNIZATION EFFORT THAT'S PLANNED, AND GOING ALONG VERY WELL, BUT I WANTED TO RAISE AWARENESS THAT IT'S HAPPENING IN CASE YOU MIGHT HEAR OF PEOPLE OR IF YOU'VE BEEN TRYING TO LOOK FOR INFORMATION THAT MAY NOT BE ON THE GARD WEBSITE, WE PLAN TO HAVE THIS UP AND RUNNING EARLY NEXT YEAR IN CALENDAR YEAR 2023. EARLY ON MAYBE FEBRUARY, MARCH, WHAT WE'RE ANGLING FOR. CERTAINLY WE HOPE THAT THIS WILL BE REALLY IN PLACE BY RARE DISEASE DAY. SO WHERE ARE WE IN THE PROCESS? WE'VE TRANSFERRED GARD TO A NEW PLATFORM FOR A BETTER USE EXPERIENCE. AND THEN THAT'S COMPLETE, SO PATIENTS OR FAMILIES CAN CALL OUR CONTACT CENTER AND THERE'S NO HICCUPS THERE. THE PHASE 3 ASPECT IS THAT WE'RE REBUILDING THE WEBSITE TO OFFER MORE INFORMATION CONTENT ON MORE RARE DISEASES, SO WE'RE HOPING TO BUILD AND EXPAND THE CONTENT WE HAVE ON HERE. WE HOPE THIS WILL ALLOW USERS TO GET BETTER UNDERSTANDING OF THE DISEASES THAT THEY ARE INTERESTED IN, AND UNDERSTAND MORE CLEARLY DIAGNOSTIC ODYSSEY AND WHAT WE KNOW ABOUT THE PARTICULAR DISEASE THEY HAVE QUESTIONS ABOUT. SO, WE HAVE TWO WEBSITES THAT I'VE PUT ON QR CODES, ONE IS THE LINK TO THE WEBSITE AND CURRENT INSTANTIATION, AND A FEEDBACK FORM, AND WE'D LOVE TO HAVE YOUR FEEDBACK. WE'RE STILL IN THIS TIME FRAME OF CONTINUING TO ITERATE ON THAT FEEDBACK AND HELP MAKE THIS NEXT MODERNIZATION OF GARD SEEN WHEN IT'S READY TO GO EARLY NEXT YEAR. PLEASE TAKE A LOOK IF YOU HAVE A MOMENT AND SEND US YOUR FEEDBACK. NEXT SLIDE PLEASE. YOU MIGHT RECALL LAST TIME WE MET, I TOLD YOU ABOUT THE NLP CHALLENGE AND HOW IT RESULTED IN A VARIETY OF WINNERS FROM ACROSS THE GLOBE, AND NCATS HAS SECURED EIGHT SOFTWARE SYSTEMS TO USE IN THE FUTURE INSTANTIATION OF WHAT THIS PROGRAM WILL LOOK LIKE. LITCOIN HAS THE POTENTIAL TO FUNDAMENTALLY CHANGE THE WAY RESEARCHERS PUBLISH THEIR WORK, HOPING IT WILL BE EASIER AND THAT THERE WILL BE MORE INFORMATION TO MINE AND INTEGRATE INTO MORE THINKING IN UNDERLYING SCIENTIFIC QUESTIONS. TYLER BECK WITH CHRISTINE COLVIS HAS BEEN USHERING THIS FORWARD, HAS DONE AN AMAZING JOB. NEXT STEP IS THE PILOT DESIGN CHALLENGE, AND THIS IS FOCUSED ON THE PLATFORM AND ASSOCIATED REQUIREMENTS NEEDED TO BUILD THIS PROPOSED SYSTEM, AND SO THIS CHALLENGE IS GOING TO BE OPEN UNTIL OCTOBER 31, SO YOU HAVE SOME TIME IF YOU'RE INTERESTED. WE EXPECT TO AWARD $5,000 FOR THE TOP FIVE RATED DESIGNS SUBMITTED. AND THEN WE WILL TAKE A LOOK AT WHAT THOSE DESIGNS ARE AND DEVELOP THE FUTURE CONTRACTS FOR IMPLEMENTING THESE DESIGNS INTO A SYSTEM IN THE COMING YEARS. SO THIS IS REALLY THE DEVELOPMENT PHASE OF WHAT LITCOIN WILL TURN INTO ULTIMATELY. NEXT SLIDE PLEASE. I'VE HAD THE OPPORTUNITY TO ATTEND THE THE HEBER MEETING TWO WEEKS AGO. WHEN FRANCIS COLLINS LEFT HE AND LARRY ASKED ME TO JOIN THIS MEETING THIS YEAR TO GO TO THE HEVER MEETING, A VARIETY OF R&D LEADERS FROM INDUSTRY SECTORS OR COMPANIES. A LOT OF TIMES WHAT COMES OUT OF THE MEETINGS CAN BE TURNED INTO SOME PROGRAMS WITHIN THE NIH AND ACCELERATED MEDICINES PROGRAM HAS BEEN ONE THAT'S BENEFITED A LOT FROM THESE KINDS OF DISCUSSIONS. IN FACT, WHEN FRANCIS WENT A FEW YEARS AGO HE PROPOSED THE BESPOKE GENE THERAPY CONSORTIUM, AND OUT OF THAT CAME THE AMP BGTC WHICH I'LL COMMENT ON IN JUST A MOMENT, BUT IT'S THOSE TYPES OF OPPORTUNITIES THAT THESE DISCUSSIONS CAN REALLY ENABLE. SO HAD THE OPPORTUNITY TO GO THERE AND SOME DISCUSSIONS WERE ABOUT ARTIFICIAL INTELLIGENCE AND ADVENT OF ALPHA-FOLD AND HOW WE CAN BRING THAT INTO DRUG DEVELOPMENT. MORE TO COME I'M SURE AS THE YEARS CONTINUE WITH THESE PROGRAMS ACROSS OUR SECTORS. NEXT SLIDE PLEASE. A COUPLE UPCOMING MEETINGS WITH NCI, NINDS, NIAID. WE WILL BE HOSTING THIS MEETING ON THE QUEST FOR INNOVATIVE MOLECULAR TREATMENT MODALITIES, FALLING UNDER OUR ONE OF OUR AUDACIOUS GOALS UNDER MORE TREATMENTS. IT IS REALLY TO THINK ABOUT IDENTIFYING PAIN POINTS FOR DEVELOPING TREATMENTS AGAINST TARGETS THAT ARE REALLY VERY DIFFICULT TO TREAT, ESSENTIALLY INTRACTABLE NOW. WHAT ARE SOME CURRENT METHODS WE CAN USE TO REALLY PUSH FORWARD ON DRUG DISCOVERY, SO THIS WORKSHOP IS GOING TO BE FOCUSING ON IDENTIFYING PROTEIN FAMILIES, ENTITIES, DISEASE AREAS THAT ARE REALLY MOST IN NEED FOR INNOVATIVE THERAPEUTIC MODALITIES. AND WE HOPE THAT'S THE DISCUSSIONS WILL TURN INTO SOMETHING WE CAN PURSUE FOR FUTURE OPPORTUNITIES. AND EXPANDING REALLY REPERTOIRE OF THERAPEUTIC APPROACHES FOR TREATING THESE INTRACTABLE DISEASES. NEXT SLIDE PLEASE. ANOTHER MEETING TO MENTION IS ON MINIMIZING BIAS AND MAXIMIZING LONG-TERM ACCURACY OF PREDICTING ALGORITHMS IN HEALTH CARE. SO, THIS PARTICULAR MEETING FALLS WELL UNDER THE ALL PEOPLE AUDACIOUS GOAL. A.I. AND M.L. ALGORITHMS, WE'VE TALKED ABOUT THEM A LOT. THEY HAVEN'T SHOWN THEIR FULL POTENTIAL IN CLINICAL APPLICATIONS, CLINICAL DECISION SUPPORT, THINGS OF THAT NATURE. EVEN WELL-SIGNED ALGORITHMS, A.I. ALGORITHMS AND MODELS, CAN BECOME INACCURATE OVER TIME, UNRELIABLE. AND DUE TO A VARIETY OF FACTORS, WE CAN CHANGE HOW DATA GETS CAPTURED, DISTRIBUTED, HOW BEHAVIORS OF HOW DATA ARE USED, HOW REAL WORLD INTERACTIONS UNFOLD. ALL THESE THINGS CAN CAUSE MINOR SHIFTS, BUT ADD UP INTO MAJOR SHIFTS OF WHAT HAPPENS IN DEGRADING THESE ALGORITHMIC PRACTICES. THIS IS AN EFFORT TO ADDRESS THESE ISSUES, TO IMPROVE THE CLINICIAN/PATIENT TRUST, BUT EVEN MORE SO THE CLINICIAN TRUST IN USING A.I. ALGORITHMS FOR THINKING ABOUT CLINICAL DECISION SUPPORT TOOLS. THIS IS A CHALLENGE THAT'S GOING TO INVITE GROUPS TO DEVELOP BIAS DETECTION METHODS OR CORRECTION TOOLS THAT FOSTER THOSE GOOD ALGORITHMIC PRACTICES AND TO MITIGATE THOSE CONCERNS THAT WE HAVE ABOUT THESE MOVING FORWARD. SO, THIS IS COMING SOON. WE DON'T HAVE MANY DETAILS ON THIS YET, BUT IT WILL BE OPEN FOR SUBMISSIONS AROUND OCTOBER 30, SO PLEASE STAY TUNED AND BE ON THE LOOKOUT FOR THAT IF YOU'RE INTERESTED. LAST WORKSHIP I'LL MENTION IS DEALING WITH THIS IDEA OF MOVING QUICKLY ACROSS TRANSLATIONAL SCIENCE PIPELINE, ASSAY GUIDANCE WORKSHOP ON HIGH-THROUGHPUT AND LEAD DISCOVERY, COVERING A BROAD RANGE OF CLINICAL CONCEPTS UNDERLYING ASSAY DEVELOPMENT THAT WILL HOPEFULLY ALLOW MORE HIGH-THROUGHPUT SCREENING AND REDISCOVERY PROJECTS TO BE PURSUIT AND SO THIS IS GOING TO BRING IN PARTICIPANTS WITH A BROAD ARRAY OF BACKGROUNDS AND PROVIDE PRACTICAL PERSPECTIVES ON ASSAY DEVELOPMENT AND THAT SORT OF THING. IF YOU'RE INTERESTED HERE, QR CODE IS THERE AND YOU CAN REGISTER AT THAT LINK. NEXT SLIDE PLEASE. MIKE KURILLA WILL TALK ABOUT THE CTSA PROGRAM, SO I WON'T TALK ABOUT THE PROGRAM, BUT THERE WILL BE A 2022 IN-PERSON CTSA PROGRAM ANNUAL MEETING, WE'RE EXCITED TO HAVE THAT BACK IN PERSON. ROD CALIFF WILL KICK OFF AND I'LL ROUND IT OUT AT THE END, LOOKING FORWARD TO HAVING THIS MEETING IN PERSON AND DISCUSSING ACHIEVING HEALTH EQUITY THROUGH SCIENCE OF TRANSLATION. NEXT SLIDE PLEASE. THERE ARE TWO FUNDING OPPORTUNITIES THAT I WANTED TO RELAY AS WELL FOR THE FULL LIST GO TO THE QR CODE HERE. WHO RARE DISEASE FOCUSED FOAs TO SHOW YOU TODAY, ONE FROM THE RARE DISEASE DIVISION, OTHER FROM PROGRAM DEVELOPMENT, TARGETING RARE DISEASES AND ONE IS ON SHARED MOLECULAR ETIOLOGIES, THIS IDEA OF LOOKING AT WHAT'S COMEN TO UNDERSTAND WHERE MODALITIES MIGHT FIT BEST. AND THEN SECOND IS ON -- SMALL PROGRAMS JUST INVESTIGATING UNDERSTUDIED PROTEINS ASSOCIATED WITH RARE DISEASES. THIS IS REALLY A SPINOFF FROM THE FANTASTIC WORK THAT CARLY SHARMA HAS DONE THROUGH THE COMMON FUND, APPLYING THE WORK THAT'S BEEN DONE IN THAT SPACE TO NOW PUSHING THAT INTO THE RARE DISEASE SPACE. I WANTED TO MENTION THOSE TWO SPECIFICALLY. NEXT SLIDE PLEASE. I WANT TO ALSO MENTION WHILE WE'RE ON RARE DISEASES HERE TOO, P.J. BROOKS LEADS A COMMON FUND PROGRAM ON THE SOMATIC GENE EDITING PROGRAM, IN ITS -- THE COMMON FUND PROGRAMS ARE TEN YEARS, THIS IS THE SECOND FIVE YEARS OF THAT TEN YEARS NOW UNDERWAY. AND SO I WANTED TO BRIEFLY MENTION, NEXT SLIDE, A COUPLE OF PROGRAMS HERE FOR THIS NEXT FIVE YEARS. THERE'S BEEN A LOT OF -- I SHOULDN'T SAY A LOT BUT THERE'S BEEN PROMISING RECENT WORK ON CRISPR BASED THERAPIES FOR LIVER, EYE, NOW APPEARING IN THE CLINIC WITH POSITIVE RESULTS. AND THERE'S BEEN EX VIVO EDITING TRIALS. THERE'S NOT BEEN NIH-SPONSORED FOR IN VIVO THERAPIES, WE'RE GOING TO CHANGE THAT. THIS IS A PROGRAM TO SUPPORT IND-ENABLING STUDIES FOR THIS WORK AS WELL AS PLATFORM CLINICAL TRIALS, GENOME EDITING FOR MULTIPLE DISEASES. THAT PLATFORM CLINICAL TRIAL FOA IS OUT UNTIL NOVEMBER 10, THE OTHERS HAVE CLOSED BUT THIS IS OPEN UNTIL NOVEMBER 10 SO I WANTED TO RELAY THAT AS WELL. NEXT SLIDE PLEASE. I'LL TURN OVER INTO A FEW -- OH, BEFORE I GO TO MY PROGRAM UPDATES, I WANTED TO MENTION THAT WE HAVE -- WE HAD AN EXCITING MOMENT WITH THE CHILDREN'S INN AT THE NIH. WE WERE ABLE TO HOST A DINNER AT THE CHILDREN'S INN AND SERVE THE COMMUNITY THERE. AND WE HAD A DELIGHTFUL TIME WORKING WITH THE STAFF AT THE CHILDREN'S INN AND ALSO WITH THE FAMILIES STAYING THERE. AS YOU KNOW, IT IS A PLACE WHERE FAMILIES CAN GO TO STAY WHILE THEY ARE GETTING -- THEIR CHILDREN OR FAMILY MEMBERS ARE GETTING TREATED AT THE NIH. MARK HENDERSON, JESSICA BADGER, MYSELF, JOINED FOR SERVING DINNER. THEY JUST OPENED BACK UP. IT'S BEEN A LONGSTANDING TRADITION AT THE CHILDREN'S INN TO HAVE DIFFERENT GROUPS COME IN AND SERVE DINNER BUT IT'S BEEN CLOSED DUE TO THE PANDEMIC. SO WE WERE GRATEFUL TO HAVE AN OPPORTUNITY TO SLIDE IN THERE AND BE ABLE TO SERVE THE CHILDREN DINNER. I WANTED TO JUST THANK JESSICA AND MARK ALSO FOR THAT ACTIVITY AS WELL. AND FOR THE ORGANIZATION. I THINK WE'LL DO MORE OF THIS SO STAY TUNED. NEXT SLIDE PLEASE. I'LL TURN IT OVER INTO PROGRAM UPDATES HERE. WE CAN GO TO THE NEXT SLIDE. I WAS TALKING ABOUT GENE EDITING. I WANT TO SHIFT GEARS QUICKLY TO TALK ABOUT GENE THERAPY. THIS IS OUR ADENO-ASSOCIATED VIRAL GENE PROGRAM, BESPOKE CONSORTIUM, ONE OF THOSE THINGS THAT CAME OUT OF HEVER DISCUSSIONS FROM BEFORE. IT HAS A LOT OF PARTNERSHIPS WITH INDUSTRY. WE'RE EXCITED TO SEE THE NUMBER OF INDUSTRIES WHO SIGNED ON, IN ADDITION THERE ARE 11 NIH INSTITUTES AND CENTERS WHO HAVE SIGNED ON. THAT IS GENERALLY UNPRECEDENTED FOR AN AMP PROGRAM WITHIN THE NIH SO WE'RE EXCITED TO HAVE ALL OF OUR PARTNERS HELPING US WITH THIS. P.J. BROOKS LEADS THE WAY HERE WITH OUR PFIZER COUNTERPART, AND I SHOULD ALSO SAY THAT THIS INCLUDES PETER MARX, WHO IS JUST VERY MUCH IN INVOLVED IN THIS PROGRAM AND WITHOUT HAVING THAT FDA LEADERSHIP I THINK IT WOULD BE MORE DIFFICULT BUT WITH FDA INVOLVED I HAVE HIGH HOMES FOR THIS PROGRAM. THERE HAVE BEEN A VARIETY OF PROGRAMS THAT HAVE BEEN AWARDED AND NOW UNDERWAY, RELATED TO AAV SOILING, -- BIOLOGY, HOW TO GET DOSAGES BETTER. RIGHT NOW DOSAGE REQUIREMENTS, THEY ARE DIFFICULT TO MANAGE AND CAN RESULT IN MORE UNTOWARD SIDE EFFECTS, SO WE HOPE TO REDUCE THAT, DOSAGE NEEDS, IDEA OF EMPTY CAPSIDS THAT HAPPENED WITH AAV GENE THERAPIES. WE'RE CELLING CMC, PRE-CLINICAL PROPOSALS AS WELL. BUT WHAT I REALLY WANT TO TELL YOU ABOUT TODAY IS THAT WE'RE UNDERGOING A DISEASE NOMINATION PROCESS, AND IT'S BEEN GOING ON FOR OVER THE PAST COUPLE MONTHS. AND IF YOU GO TO THE NEXT SLIDE PLEASE, THE UPSHOT IS THAT WE HAD 61 DISEASE NOMINATIONS THAT WERE SUBMITTED TO US. WE HAD A PROCESS BY WHICH WE NOMINATED JUST THE TOP FEW AND ENDED UP WITH THE TOP 14 DISEASE NOMINATIONS. THEY ARE SHOWN HERE. AND THE FUNDING OPPORTUNITY IS OPEN UNTIL OCTOBER 31, THAT DATE IS NOT ON HERE UNFORTUNATELY, BUT IF YOU GO TO THE QR CODE YOU'LL SEE THAT. WE'RE HOPING TO SEE GOOD SUBMISSIONS FOR THIS OPPORTUNITY TO REALLY PUSH FORWARD ON THESE DISEASE NOMINATIONS. WE WON'T BE ABLE TO SELECT THEM ALL, IT WILL PROBABLY BE A THIRD OF THESE OR SO THAT WILL MOVE FORWARD, AND I'M EXCITED THAT WE'LL HAVE THIS UNDERWAY, AT LEAST KNOWN BY THE NEXT TIME WE MEET AND GET TO TELL YOU MORE. BUT THIS HAS BEEN A PROGRAM THAT'S MADE A LOT OF PROGRESS OVER THE LAST COUPLE MONTHS AS WELL. NEXT SLIDE PLEASE. SO, LAST TIME AT OUR MEETING I MENTIONED THAT THROUGH OUR THERAPEUTICS DEVELOPMENT BRANCH THERE WAS A DRUG APPROVAL, OUR FIRST. I'M PROUD TO RELAY THE SECOND, AND THIS WAS -- AJILLU WAS ACQUIRED, THIS IS THE FIRST FOR AADC, INFUSED DIRECTLY INTO THE BRAIN. AND OUR COLLEAGUES WITH DON LO HAVE DONE A LOT OF HEAVY WORK, HEAVY LIFTING HERE, WITH THESE PARTNERS TO GET THIS UNDERWAY. NOW IT'S APPROVED BY THE FDA AS WELL AS EMA FOR EUROPEAN COUNTERPARTS. A CASE STUDY HAS BEEN WRITTEN, MAYBE ANDREW CAN PUT THAT INTO THE CHAT IF HE GETS A CHANCE AS WELL. WE'RE EXCITED ABOUT THIS. NEXT SLIDE PLEASE. SO SOME OTHER PROGRAM UPDATES, IN JULY OF THIS YEAR, TWO PROJECTS TOOK SECOND FLIGHT INTO THE ISS NATIONAL LAB. AND ONE PROJECT IS STUDYING THE CAUSES OF MUSCLE WASTING AND WHETHER CHANGES DUE TO MUSCLE WASTING CAN BE PREVENTED. OR HOW WE CAN FIND MECHANISMS THAT COULD PREVENT MUSCLE WASTING. SECOND PROJECT FROM UCSF IS INVESTIGATING IMMUNE AGING, IMMUNE SENESCENCE, AND THEN HEALING OUTCOMES FROM THAT. SO, TWO EXCITING PROJECTS GOING UP. WE HAVE A COUPLE MORE IN THE QUEUE. NEXT LAUNCH IS SCHEDULED FOR I BELIEVE NEXT MONTH, AND THAT'S GOING TO CLOSE OUT OUR LAUNCH SCHEDULE FOR THIS PROGRAM. BUT IT'S BEEN VERY EXCITING TO WORK WITH NASA AND OUR SPACE STATION NATIONAL LAB COLLEAGUES ON THIS AS WELL. HOPEFULLY WE HAVE MORE INFORMATION TO SHARE AS WE GET THESE BACK FROM SPACE AND COMPARE TO GROUND WORK ONGOING, WHATEVER THEY DO IN SPACE THEY DO ON THE GROUND TO COMPARE ALONG THE WAY AND FIND THESE DIFFERENCES TO SEE IF THERE ARE MICRO GRAVITY RESPONSES IN THAT ENVIRONMENT CONTRIBUTING TO THESE ISSUES AND CAN WE LEARN FROM THAT TO START TO BUILD THERAPEUTICS. NEXT SLIDE PLEASE. ONE OTHER ANNOUNCEMENT TO MAKE HERE ABOUT AN EXCITING PROGRAM FROM, AGAIN, DPI IS THAT THIS IS LED BY ANTON SIMEONOFF, BUILDING A LIBRARY OF SYNTHETIC NANOBODIES, WE HOPE THESE WILL BE THE FODDER FOR NOVEL THERAPEUTICS MOVING FORWARD. HE'S DEVELOPED THIS LIBRARY TO HELP SPEED THE IDENTIFICATION AND DEVELOPMENT OF THESE NANOBODIES, INTO PRE-CLINICAL EVALUATION. AND THEN ULTIMATELY TO CLINICAL APPLICATIONS. THIS PAPER IS ALSO TIGHTLY CONNECTED WITH IP ASSET, THAT NCATS OFFERED TO THE WORLD HEALTH ORGANIZATION TO HELP PROVIDE LICENSES TO MANUFACTURERS ACROSS THE GLOBE TO USE THESE TECHNOLOGIES, SO THIS IS ONE WAY WE CAN DISSEMINATE THE DEMONSTRATED WORK WE'VE DONE IN DPI, SO VERY EXCITED ABOUT THIS FROM DPI, WHILE WE'RE TALKING ABOUT COVID HERE, THIS IS THE OPEN DATA PORTAL WHICH I MENTIONED BEFORE, I WANTED TO SHOW A QUICK UPDATE. JUST AS YOU RECALL, THIS IS A PORTAL COLLECTING THERAPEUTIC DATA ON SARS-COV-2 VARIANTS AND HOW THE DIFFERENT VACCINES AND THERAPEUTICS ARE WORKING AGAINST THE NEW VARIANTS. SO EACH DOT HERE REPRESENTS A PARTICULAR VARIANT THAT'S IN THE LEGEND ABOVE. YOU CAN SEE MOST OF IT IS DOMINATED BY OMICRON VARIANT, YELLOW, AND MANY SUBLINEAGES. IT'S HARDER TO SEE. WHAT WE'VE DONE, NEXT SLIDE, THINKING ABOUT HOW TO LOOK AT THIS DIFFERENTLY. WHEN YOU PARSE OUT BY TIME, AND LOOK AT THE ALPHA VARIANT, BETA, OMICRON VARIANT, YOU CAN SEE THIS WANING OF EFFECTIVENESS OF MONOCLONAL ANTIBODIES AS VARIANTS CONTINUE TO EVOLVE WITH OMICRON, THIS IS ALL IN VITRO DATA, EVASHIELD MAY STILL BE WORKING IN OMICRON BUT IT LOOKS LIKE IT'S WANING. THE BEVTOMAL IS LEFT HERE. ANTI-VIRALS ARE CRITICAL, VACCINE APPROACHES ARE CRITICAL. THE MORE PIPELINES, THERE'S A NEED THAT CONTINUES TO NEED TO BE PURSUED. THIS IS AN EXCITING OPPORTUNITY IN MONOCLONAL ANTIBODIES. I'D LIKE TO TAKE OUR NC3 DATABASE AND SEE HOW PRESCRIBING PRACTICES COMPARE TO WHAT WE'RE SEEING IN THE WANING OF USEFULNESS OF MONOCLONAL ANTIBODIES AND HOW IT'S WORKING IN THE REAL WORLD. WE'RE DEVELOPING A MONKEYPOX PAGE, IT LOOKS TO BE WANING, HOPEFULLY IT IS, BUT WE'LL BE POPULATING THIS AS WELL. NEXT SLIDE PLEASE. I MENTION NC3, A QUICK UPDATE, WE'RE OVER 15 MILLION RECORDS WITH, OVER 6 MILLION COVID-POSITIVE CASES, THAT'S CONTINUING TO GROW. AND WE NOW HAVE OVER 3,000 RESEARCHERS WITHIN THE ENCLAVE LOOKING AT A VARIETY OF RESEARCH QUESTIONS. SO, AGAIN, ENCOURAGE YOU TO TAKE A LOOK AT THE DASHBOARD IF YOU HAVEN'T ALREADY AND LOOK AT THE NEW DATA THAT WE HAVE IN THERE. JUST MENTIONING A FEW, NEXT SLIDE, THAT WE'VE BEEN DOING WITH THIS, IT HAS GOTTEN SOME ATTENTION. WE RECEIVED A PHONE CALL FROM THE WHITE HOUSE OFFICE OF THE COVID RESPONSE COORDINATOR, ASKING US TO LOOK AT PAXLOVID, PEOPLE WERE TALKING ABOUT THE REBOUND EFFECT, THEY WERE CONCERNED ABOUT THAT. IN JUNE WE PULLED OUR DATA, AT THE TIME HAD 22,000 PEOPLE PRESCRIBED PAXLOVID, VERY SMALL NUMBERS WHO STARTED PAXLOVID ENDED UP IN A HOSPITALIZATION CATEGORY, A FEW WEEKS AFTER USING PAXLOVID. THAT'S A VERY SMALL NUMBER, LESS THAN A PERCENT HAD SEVERE OUTCOMES ASSOCIATED WITH THAT PAXLOVID USE. AGAIN, IT'S NOT ASSOCIATED, IT MAY BE CIRCUMSTANTIAL. THE BEHAVIOR OF THE VIRUS ITSELF COULD BE CAUSING MANY EFFECTS, IT'S PROBABLY MORE THAT. WHAT WE FOUND IN FACT WAS THAT THAT'S PROBABLY THE CASE BECAUSE PEOPLE WHO ARE OLDER OR HAD MORE COMORBIDITIES TENDED TO HAVE THESE MORE SEVERE OUTCOMES DESPITE USING PAXLOVID. SO THIS LOOKS TO BE A VIRAL CHARACTERIZATION MORE THAN ANYTHING, USEFUL INFORMATION WE COULD RELAY TO THE WHITE HOUSE OFFICE OF THE COVID RESPONSE COORDINATOR. I SHOULD ALSO MENTION THAT THIS HAS BEEN NOW IN MedRxiv TO ANOTHER GROUP ASKING SIMILAR QUESTIONS. IN THE BACKGROUND OF ALL OF THIS AS WELL WE'VE BEEN WORKING CLOSELY WITH THE TRIBAL COMMUNITY TO UNDERSTAND HOW USE AMERICAN INDIAN AND ALASKA NATIVE DATA, IT'S A RACIAL CATEGORY COLLECTED WITH THE RACIAL DATA, BUT WE WERE SENSITIVE TO MAKING SURE WE COMMUNICATED WITH THE TRIBAL GROUPS TO MAKE SURE THAT WE WERE UNDERSTANDING HOW BEST TO USE THESE DATA IN THIS WAY. AND SO WE DID A VARIETY OF COMMUNICATIONS AND CONSULTATIONS WITH THE TRIBAL ADVISORY COMMITTEE AND TRIBAL CONSULTATION GROUP. THE UPSHOT IS THAT WE HELD THESE CONSULTATIONS AND THEN RECEIVED WRITTEN TESTIMONY FROM THE TRIBAL NATIONS, TO PROVIDE INPUT ON OUR PLANS. AND THEN WE MET WITH THEM MOST RECENTLY IN AUGUST TO GIVE THEM AN UPDATE OF HOW WE'RE GOING TO UNFOLD OR PURSUE THE INTEGRATION OF AMERICAN INDIAN AND ALASKA NATIVE DATA WITHIN THE DATABASE, IT'S BEEN A VERY FRUITFUL CONVERSATION AND WE'RE CONTINUING THAT CONVERSATION. I THINK IT'S A "YES AND," CONTINUING TO WORK TO SEE WHAT MORE WE CAN DO. IF YOU'RE INTERESTED IN THESE REPORTS I'VE GIVEN YOU THE QR CODES SHOWN HERE. IT'S BEEN AN IMPORTANT ENGAGEMENT THAT WE'VE UNDERTAKEN WITH THIS GROUP. NEXT SLIDE PLEASE. WITH THIS I WILL SAY WE HAVE CHANGED SOME OF OUR PILLARS OF DATA PROTECTION AND I THINK CHANGED IN A VERY GOOD WAY, A STRONG WAY. AND ESSENTIALLY JUST MAKING SURE THERE'S AWARENESS WITH THE RESEARCH COMMUNITY, THAT THERE ARE SOME SENSITIVITIES BEHIND USING AMERICAN INDIAN AND ALASKA NATIVE DATA AND WANTING THEM TO BE AWARE. FULL FIVE-DIGIT ZIP CODES WILL NEVER BE SHOWN FOR THE AI/AN DEMOGRAPHIC DATA TO ENSURE PRIVACY, FOR EXAMPLE, THAT'S ONE OF THE PROTECTIONS WE'RE ADDING AND PUTTING IN PLACE TO ENSURE THESE DATA CAN CONTINUE TO MOVE FORWARD. THE WHOLE IDEA OF COURSE IS THAT ALL COMMUNITIES CAN USE THESE DATA AND ASK QUESTIONS THAT ARE VERY RELEVANT FOR THEM. AND THAT'S OUR REAL GOAL HERE, ALLOWING THESE FOUR PILLARS OF DATA PROTECTIONS TO BE EXPANDED IN THIS WAY I THINK IS VERY GOOD AND VERY NEEDED. NEXT SLIDE PLEASE. I'M GOING TO END ON JUST A FEW COMMENTS ABOUT FNIH AND WORK THERE. PAULA, YOU HAVE YOUR HAND UP. WOULD YOU LIKE TO JUMP IN? >> I HAVE A QUESTION. ALL FOR NOT SHOWING THE ZIP CODES BUT WILL THEY SAY YOU NEED CENSUS BLOCK FOR ADI BUT THINGS LIKE THE SOCIAL DEPRIVATION INDEX AND ALL OF THAT BE AVAILABLE, DE-IDENTIFIED BY LOOKING AT A DIGIT OR TWO. >> RIGHT. AND SO FOR THE WAY THAT WE'RE PURSUING THIS, IT WILL BE THREE-DIGIT ZIP CODES FOR AREAS OVER 20,000 PEOPLE IN THEM, OUR CUTOFF IS 20,000 PEOPLE WITHIN A ZIP CODE AREA. FEWER THAN 20,000, THAT CAN BE IDENTIFIED TO A SPECIFIC TRIBE, AND THAT'S SOMETHING THAT WE DON'T WANT TO DO. SO FOR AI/AN, THAT'S HOW WE'RE PURSUING THAT. FOR OTHER DATA, THERE WILL BE FULL FIVE-DIGIT ZIP CODES AVAILABLE. >> EVEN THREE-DIGIT ZIP CODE, EVEN ZIP CODE IS NOT USEFUL IF WE'RE GOING DOWN TO SOCIAL DETERMINANTS OF HEALTH. WHAT I'M WONDERING IS IF YOU HAVE THE DATA OR IT COULD BE LIKE THE AREA DEPRIVATION INDEX, JUST A NUMBER, AND YOU COULDN'T IDENTIFY WHERE THEY CAME FROM BUT YOU HAVE THE ADI, GOES TO 0-100 OR SOMETHING LIKE THAT COULD BE IN THE DATA SO THAT YOU CAN'T IDENTIFY THEM BUT YOU HAVE THE INFORMATION. >> THAT'S RIGHT. AND GREAT POINT, THIS IS EXACTLY A POINT THAT CAME UP DURING THE TRIBAL CONSULTATIONS AS WELL. IS THERE AN OPPORTUNITY TO DO THIS IF IT'S NEEDED? AND SO, THE PROTECTIONS ARE IN PLACE, BUT THERE WOULD BE THE WAYS IF WE CONTINUE THE CONVERSATIONS THAT WOULD CERTAINLY BE POSSIBLE. YEAH, IT'S A GOOD POINT. ERRING ON PROTECTION BUT HAVING ABILITY TO DO SO IF THAT'S AGREED UPON FOR THESE STUDIES. ALL RIGHT. TO FNIH, SO THE PARTNERSHIP HAS BEEN CRITICAL FOR ADVANCING OUR UNDERSTANDING OF THE COVID-19 THERAPEUTICS AND VACCINES. THAT'S WHAT THE ACTIV ACRONYM IS FOR, AN UNPARALLELED PARTNERSHIP WHEN THE PANDEMIC FIRST STARTED. I'LL GIVE A BIG OVERVIEW OF WHAT ACTIV HAS DONE TO DATE. AND I'LL TALK ABOUT THE NCATS. NEXT SLIDE PLEASE. THIS IS AN OVERVIEW OF REALLY UNDERSTANDING THAT WE WERE WANTING TO ADDRESS EVERY STAGE OF THE CLINICAL STAGES OF THE COVID-19 DISEASE. AND THEN ATTACKING THOSE STAGES THROUGH THE CLINICAL TRIAL PROTOCOLS THAT WE PUT INTO PLACE. THOSE ARE THE ACTIV PROTOCOLS THAT WE HAVE IN PLACE. THERE HAVE BEEN SIX OF THEM, WITH SUBSETS UNDERNEATH. AND ACROSS THAT, AGAIN, THE STAGES HERE. SO WE WANTED TO DETERMINE WHICH THERAPEUTICS STRATEGIES WORK OR DON'T WORK IN CLINICAL SETTINGS AND MOVE FORWARD. NEXT SLIDE PLEASE. OH, NCATS DID ACTIV 1 AND 6 SPECIFICALLY. NEXT SLIDE. THIS IS THE UPSHOT, ALL DATA ON ONE SLIDE, WE'VE HAD OVER 20,000+ PATIENTS ENROLLED IN ACTIV, 620 SITES, MULTIPLE NETWORKS, ET CETERA, INCLUDING CTSA PROGRAM AS WELL. 28-- SORRY, 26 SCIENTIFIC PUBLICATIONS, A COUPLE RECENTLY ACCEPTED SO I JUMPED THERE, BUT 26 IN PRESS. SORRY, PUBLISHED. AND THEN THOSE HAVE BEEN CITED OVER 500 TIMES. WE'VE LOOKED AT 800 AGENTS, 29 AGENTS -- 800 EVALUATED, AND WE'VE LOOKED AT 29 AGENTS THROUGH THESE PROTOCOLS. SIX HAVE PROVEN EFFICACIOUS. NEXT SLIDE I'LL GIVE A SENSE OF WHAT THOSE ARE. THESE ARE ALL OF THE AGENTS WE'VE TESTED, THE ONES IN RED SHOW LACK OF EFFICACY, IN GREEN HAVE SHOWN EFFICACY. LIGHT GREEN THEY MISSED PRIMARY ENDPOINT BUT SHOWED EFFICACY IN SECONDARY ENDPOINTS. SO, THIS HAS BEEN REALLY AN AMAZING AMOUNT OF WORK ESPECIALLY THINKING ABOUT MANY OF THESE DRUGS WERE REPURPOSED, AND WE WERE ABLE TO EVALUATE THEM QUICKLY FOR COVID-19. NEXT SLIDE PLEASE. A QUICK RUNDOWN OF ACTIV-1 AND 6, 1 LOOKS AT IMMUNOMODULATORS, KEY SECONDARY ENDPOINTS LOOKED VERY GOOD, MISSIONED PRIMARY. THERE WAS A 40% AVERAGE LOWER ODDS OF DYING COMPARED TO PLACEBO, AND FOR THE SECONDARY ENDPOINT 43% ANDS 34% ODDS OF CLINICAL IMPROVEMENT COMPARED TO PLACEBO. ONE WAS STOPPED EARLY ON DUE TO LACK OF EFFICACY, I HOPE WE GET THESE IN THE TREATMENT GUIDELINES MOVING FORWARD. NEXT SLIDE PLEASE. ACTIV-6, THE CLINICAL TRIAL FOR THE PEOPLE, AND OF THE PEOPLE, BECAUSE THERE WERE A LOT OF REQUESTS TO LOOK AT IVERMECTIN AND DRUGS REPURPOSED, TOP RESULTS FOR IVERMECTIN 400, NOW LOOKING AT 600, CLOSED, DOING DATA CLEANING NOW. AND FOR 400 THERE WAS NO MAJOR DIFFERENCE COMPARED TO PLACEBO, AND FLUTICASONE SIMILAR OUTCOMES, WE'RE AWAITING 600, AND FLUVOXAMENE COMING SOON. NIH RECOVER INITIATIVE OUT OF NHLBI. SOME IMPORTANT WORK THAT WE'RE ALSO CONTRIBUTING BUT OVERALL THE GOAL IS TO LOOK AT UNDERSTANDING CLINICAL SPECTRUM, RISK FACTORS AND INTERVENTIONS TO TREAT OR PREVENT POST-ACUTE SEQUELAE OF COVID. AND THEN CURRENTLY THEY ARE CONSIDERING CLINICAL TRIALS THAT WILL BE ONGOING AND PARTNERING WITH FNIH TO CONTINUE AS WE SPEAK, TALKING ABOUT HOW TO DO THAT AND I'VE HIGHLIGHTED THE ELECTRONIC HEALTH RECORDS SYSTEM. NEXT SLIDE PLEASE. THIS IS SOME WORK, THE FIRST PAPER PUBLISHED ACTUALLY OUT OF THE RECOVER PROGRAM, N3C PAPER. THEY FOUND THEY WERE ABLE TO PARSE OUT PHENOTYPES FOR LONG COVID, METABOLIC, CARDIO PULMONARY PHENOTYPES, AND DIFFICULTY BREATHING ASSOCIATED WITH HIGHER RISK, AND VACCINATION WAS ASSOCIATED WITH LOWER RISK OF PASC. NEXT SLIDE. CONTINUING ON WITH THIS IDEA THAT LONG COVID LOOKS TO BE UNFORTUNATELY HERE TO STAY. AND SO WE WANT TO MAKE SURE WE HAVE A GOOD EXTRA STRATEGIC PLAN IN STLAP -- A GOOD STRATEGIC PLAN IN PLACE. THE N3C WAS MENTIONED IN THE WHITE HOUSE PLAN AS PART OF THE ACTION PLAN. AND SO I WANTED TO RELAY THAT TO THIS GROUP, IN CASE YOU'RE INTERESTED IN READING IT AS WELL. NEXT SLIDE PLEASE. IN ADDITION TO WHAT RECOVER IS DOING IN TERMS OF THE ELECTRONIC HEALTH RECORD WORK, WE'RE PARTNERING WITH PCORnet AND "ALL OF US," TO LOOK AT THESE ALGORITHMS TO DETECT PHENOTYPES OF LONG COVID AND TRYING TO COMPARE THEM, UNDERSTAND WHAT'S THE SAME AND WHAT'S DIFFERENT BASED ON HOW YOU DEVELOP ALGORITHMS FROM THE ORIGINATING DATASETS. AND WE'RE USING THE "ALL OF US" COHORT TO HELP US BE THE CENTRAL PLACE WHERE WE CAN LOOK AT THESE. SO "ALL OF US" HAS BEEN WHERE WE'VE DEPLOYED THE ALGORITHMS ENTIRELY WITHIN THEIR ENVIRONMENT, AND SO THEN WE'VE BEEN ABLE TO COMPARE HOW THE N3C ALGORITHM WORKS IN THAT DATASET AND COMPARING THAT TO OTHERS. SO STAY TUNED TO HOW THESE WILL UNFOLD, WE'RE LEARNING A LOT THROUGH THIS PROCESS, AND I THINK IT'S A NICE COLLABORATIVE EFFORT WITH THESE TEAMS. NEXT SLIDE PLEASE. JUST A FEW MORE SLIDES, ONE ENDING ON THE TRAINEES WITHIN NCATS, DELIGHTED TO HIGHLIGHT A COUPLE TRAINEES, EACH YEAR OUR TRAINEES FROM OUR INTRAMURAL PROGRAM VOLUNTEER TO ENTER A THREE-MINUTE TALK, WHERE THEY DEVELOP COMPELLING SCIENTIFIC RESEARCH PRESENTATIONS AND TALK ABOUT THEM FOR THREE MINUTES. DURING OUR ANNUAL FELLOWS RETREAT WE HAVE THIS IN NHGRI, THEY DO THIS COMPETITION. AND THESE ARE JUST FANTASTIC. THEY DO A FANTASTIC JOB. ONE IN PARTICULAR HALEY CHATELAINE WAS A FINALIST. SHE'S WORKING ON NCATS METABOLOMICS OPERATIONAL WORKFLOW, MEOW, WE'RE EXCITED ABOUT THIS ASPECT OF WHAT SHE'S DOING IN THE INTRAMURAL PROGRAM FOR HER FELLOWSHIP. SO, MORE TO COME ON THE NCATS MEOW BUT STAY TUNED. NEXT SLIDE PLEASE. I ALSO JUST WANT TO GIVE A SHOUT OUT TO MARSHAL SUMMER. I WAS DELIGHTED TO BE ON THE VIRTUAL END OF WATCHING MARSHAL SUMMAR RECEIVE A LIFETIME ACHIEVEMENT WORK. HIS PASSION FOR SERVING PATIENTS IS AT THE CORE OF EVERYTHING HE DOES, MENTORSHIP FOR THE NEXT GENERATION OF MEDICAL AND BIOCHEMICAL GENETICISTS HAS BECOME HIS LEGACY. CONGRATULATIONS, REALLY EXCITING. >> IT'S THE ONLY TIME YOU'LL SEE ME WITH A TIE OR TUX. >> YOU LOOK SHARP. >> IT WAS A TEAM AWARD. I'VE GOT A PHENOMENAL TEAM HERE, BUT ABSOLUTELY. I GOT TO SAY THE WORK I'VE BEEN ABLE TO DO WORKING WITH THE TEAMS AT NIH HAS BEEN A BIG A PART AS ANYTHING TOO. I'M VERY GRATEFUL. >> NEXT SLIDE. I HAVE TO END ON A HIGH NOTE THANKS TO MARSHALL, I'LL UP FOR DISCUSSION AND HAPPY TO TAKE QUESTIONS AND THE TEAM IS AVAILABLE TO HELP OUT ANSWERING QUESTIONS AND, CLAIRE, I'LL ASK YOU TO HELP MODERATE TOO. >> WILL DO. >> ALL RIGHT. THANK YOU. MAYBE THERE AREN'T ANY. IF THAT'S THE CASE WE'LL MOVE FORWARD, AND THAT'S OKAY TOO. IT'S A QUIET BUNCH TODAY. >> ACCELERATOR PROGRAMS ARE JUST COOL. >> THEY ARE. THEY ARE. AND WE'RE REALLY EXCITED THAT THIS NEW LIBRARY IS NOW GOING TO BE PART OF THAT. MARSHALL, I HOPE YOU'RE SEEING THE CHAT. I DON'T KNOW IF YOU ARE, BUT I HOPE YOU'RE SEEING THE CHAT. YOU HAVE TO TAKE A LOOK. >> I'LL GO TAKE A LOOK. >> ALL RIGHT. ANNIE, GO AHEAD. >> I DON'T HAVE A QUESTION, JUST AN OVERALL COMMENT OR COMPLIMENT. I WOULD SAY THE IMPRESSION I HAD WHEN WE WERE REVIEWING THE GRANTS AND SUBMISSIONS THAT HAD COME IN ALSO, I'M REALLY OVERWHELMED AND BOWLED OVER BY THE WORK OF THE NCATS TEAM AND BROADER COMMUNITY THAT THE TEAM IS CATALYZING. I WOULD LIKE TO GIVE A GENERAL COMPLIMENT TO EVERYBODY, AS A REPRESENTATIVE OF THE PATIENT COMMUNITY THIS IS REALLY GRATIFYING AND REFLECTS URGENCY IN THE COMMUNITY BUT ALSO NEED FOR INNOVATION THAT REALLY DIRECTLY TRANSLATES TO OPTIMIZED HEALTH OUTCOMES FOR OUR PATIENT COMMUNITIES, AND ALSO WAS STRUCK BY THE GLOBAL REACH THAT YOUR WORK IS HAVING IN YOUR PRESENTATION, DR. RUTTER. I WOULD LIKE TO SAY THANK YOU TO EVERYBODY. CONTINUE TO PRESS ON THAT ACCELERATOR, I'M STRUCK BY THE WORD ACCELERATE ON YOUR SLIDE, BECAUSE WE NEED THAT FROM YOU BUT WE'RE GRATEFUL FOR IT. WE KNOW EVERYONE HAS BEEN STRETCHED AND PULLED, ESPECIALLY IN THE LAST YEAR AND A HALF, AND WE'RE GRATEFUL FOR THE WORK EVERYONE'S DOING. WE FEEL IT AND WE APPRECIATE IT. >> THANK YOU VERY MUCH. THANK YOU VERY MUCH. WE DON'T HAVE ALL THE STAFF ON CAMERA BUT I KNOW THEY VERY MUCH APPRECIATE THOSE COMMENTS. THANK YOU. TO YOUR POINT ABOUT THE GLOBAL PERSPECTIVE, IT'S SOMETHING I WANT TO CONTINUE TO REALLY TRY TO ADDRESS AND WE HAVE SOMETHING CALLED TRANSLATION TOGETHER, WHICH IS A PARTNERSHIP WITH A VARIETY OF DIFFERENT COUNTRIES, AND TO ME THIS IS GOING TO BE REALLY IMPORTANT AND CRITICAL FOR US ESPECIALLY IN THE RARE DISEASE SPACE, AS WE START TO BUILD ON N OF SMALL TRIALS, HOW TO MAKE SURE WE'RE INCORPORATING WHERE -- WHERE WE CAN WE CAN BRING IN PATIENTS FROM ACROSS THE GLOBE SO THAT REACH, THAT ENGAGEMENT IS SO IMPORTANT FOR OUR RARE DISEASE WORK AND THAT'S SOMETHING THAT I'D LIKE TO CONTINUE TO ENHANCE, SO THAT'S -- I GUESS THAT'S A PROMISE AND ALSO AN EXCITING AREA THAT I THINK WE CAN PURSUE VERY WELL WITHIN THE NIH, AND THEN ACROSS THOSE BOUNDARIES. COULDN'T AGREE MORE. ANY OTHER COMMENTS OR QUESTIONS? IF NOT, I'LL BE HERE ALL DAY SO KEEP THINKING. AND PERHAPS ANNA, SHOULD WE GO AHEAD AND MOVE ON TO DR. KURILLA'S PRESENTATION? >> ABSOLUTELY, JONI. >> ALL RIGHT. WELL, THANK YOU. HOPEFULLY I COULD BE AS EFFICIENT AS JONI WAS IN THAT BECAUSE WE'RE AHEAD OF SCHEDULE, OR YOU CAN JUST TAKE MY TIME AND GET US BACK ON TRACK HERE. ANYWAY, I WANT TO GIVE YOU AN OVERVIEW OF THE CTSA PROGRAM AND SO WE'LL START OUT WITH JUST A SORT OF OVERVIEW OF THIS PAST YEAR, WE'LL TALK ABOUT SOME CTSA CONSORTIUM ACTIVITIES AND THEN ACTIVITIES ADDRESSING COVID-19, JONI HIT HIGHLIGHTS IN TERMS OF THE ACTIV TRIALS BUT I'LL TALK AT THINGS AT A CONSORTIUM LEVEL AND INDIVIDUAL HUH LEVEL. THEN WE DO HAVE OUR REGULARLY SCHEDULED PROGRAM WITH NON-COVID-19. SO, I'M GOING TO START OUT TALKING IN THE NEXT SLIDE JUST TO REMARK WE HAD ISSUED THE SUITE OF -- NEW SUITE OF FOAs LAST YEAR AND WE'VE GOT OUR FIRST APPLICATIONS IN EARLIER THIS YEAR. WE'RE IN THE MIDST OF REVIEWING THE VARIOUS PROPOSALS THAT ARE COMING IN AND WE'VE STARTED TO RECEIVE FEEDBACK FROM THEM FROM VARIOUS GROUPS, INDIVIDUALS CERTAINLY HAVE NOT BEEN SHY, I DON'T KNOW ANYTHING IN THE CTSA PROGRAM IS SHY. BUT WE'VE GOTTEN COMMENTS FROM INDIVIDUALS, I'VE DONE A LOT OF CALLS WITH CTSA PODS. EACH OF THE STEERING COMMITTEE MEMBERS HAS ABOUT FIVE OR SIX CTSAs AND MEET REGULARLY AND I GO OCCASIONALLY TO THEIR POD MEETINGS WITH A SORT OF FORMAT OF ASKING ANYTHING AND WE TALK ABOUT VARIOUS TOPICS AND SOME IS FEEDBACK. ALSO, THE COALITION FOR CLINICAL AND TRANSLATIONAL SCIENCE, WHICH IS THE LOBBYING ARM OF ACTS AND C.R. FORUM PROVIDED SOME COMMENTS AND SO, YOU KNOW, AS A RESULT OF THIS WE HAVE QUITE A FEW -- EITHER WE'VE GOT EXTENSIVE AMOUNT OF CONSTRUCTIVE FEEDBACK, HAVE ISSUED NOTICES OF CORRECTION ALONG THE YEARS, OVER THE PAST YEAR, THINGS WE THOUGHT WERE WELL INDICATED BUT WERE SUBJECT TO MULTIPLE INTERPRETATIONS. WE'VE HAD A NUMBER OF TECHNICAL ASSISTANCE WEBINARS AND ANOTHER ONE SCHEDULED TO LET PEOPLE -- TO PRESENT THE NEW FORMAT AND THE NEW PROGRAM MECHANISMS. AND THEN TO ALLOW THE COMMUNITY TO ASK QUESTIONS. AND WE KEEP UPDATING AND ENHANCING OUR FAQs. AND SO THE ONE THING WE ARE IN THE PROCESS OF COMPILING IS FEEDBACK FROM THE REVIEWERS THEMSELVES, BECAUSE AS AN IMPORTANT COMPONENT IT'S NOT JUST PREPARATION OF THE APPLICATION, BUT WE WANT TO SEE THAT THE REVIEWERS ARE ACTUALLY -- GET THEIR OPINION ON HOW WELL THE FOAs ARE STRUCTURED FROM A REVIEW STANDPOINT. AND WE HOPE TO BE ABLE TO HAVE AT A LATER DATE BE ABLE TO TALK MORE ABOUT WHAT SORT OF CHANGES WE WILL INVOKE AS A RESULT OF ALL OF THE FEEDBACK. NEXT SLIDE PLEASE. SO IN TERMS OF OVERALL -- THIS IS THE OVERALL PICTURE FOR FY 22. YOU CAN SEE WHERE THE HUBS ARE LOCATED. BLUE STARS WITH ALL THE NEW AWARDS THAT WE'VE MADE THIS PAST YEAR. AND WE'RE CURRENTLY AT A TOTAL OF 63 HUBS. NEXT SLIDE. WE'VE GROWN. DCI HAS GROWN THROUGHOUT THIS YEAR. WE BROUGHT NINE NEW MEMBERS ON BOARD. SENIOR POSITIONS, CELINEA WADDEE TAKING OVER AND JOSH FESSEL, AND CHRIS HAWSHORN, AND STAFF MEMBERS THROUGHOUT HAVE HELPED US ROUND OUT OUR COMPLEMENT OF FTEs, GIVING MORE FLEXIBILITY IN TERMS OF BEING ABLE TO RESPOND TO INQUIRIES COMING IN FROM A WIDE ARRAY OF SOURCES, ESPECIALLY CONGRESSIONAL. NEXT SLIDE PLEASE. SO, I'D LIKE TO TALK ABOUT OUR PEOPLE AND WE'LL START OUT WITH SOME CONGRATULATIONS. OUR CTSAs REPRESENT THE LEADERS AND RISING LEADERS OF INSTITUTIONS AND IT'S NICE TO SEE THAT THERE'S A LOT OF EXTERNAL VALIDATION. SO, YOU CAN SEE THESE THREE LADIES HAVE BEEN ELECTED TO THE AMERICAN MEDICAL ASSOCIATION BOARD OF TRUSTEES, NATIONAL ACADEMY OF SCIENCES, AMERICAN SOCIETY FOR CLINICAL INVESTIGATION. SO NATIONAL RECOGNITION OF THE SIGNIFICANCE OF THEIR ACCOMPLISHMENTS AND THEIR CONTRIBUTIONS. NEXT SLIDE PLEASE. WE HAVE TWO YOUNGER INDIVIDUALS, ONE NAMED AN EMERGING LEADER IN HEALTH AND MEDICINE BY NATIONAL ACADEMY OF MEDICINE, AND ANOTHER HONOR BY THE NEW YORK ACADEMY OF MEDICINE AS RISING LEADER, IT'S NICE TO SEE THE NEXT GENERATION COMING ALONG. NEXT SLIDE PLEASE. AND THEN A NUMBER OF AWARDS THAT REALLY THINK DEMONSTRATED BREADTH OF THE CTSA, THESE FOUR INCLUDE TWO NURSES, ONE IS A KL 2 LEADER ON THE STEERING COMMITTEE, AND THEN ALSO INVOLVED IN DRUG DEPENDENCE, SO IT'S A NICE WIDE VARIETY OF ACTIVITIES ACROSS THE CTSA. NEXT SLIDE PLEASE. AND FOR THE VERY YOUNGEST SET, IT'S NICE TO SEE THAT OUR TRAINING PROGRAM, SO WE HAVE THREE THIS YEAR NAMED 40 UNDER 40 LEADERS IN HEALTH BY THE NATIONAL MINORITY QUALITY FORUM, AND ONE IS A CURRENT KL 2 SCHOLAR, TWO FORMER KL 2 SCHOLARS, NICE TO SEE THE PROGRAM IS NOT JUST FOCUSING PEOPLE TO BE CLINICAL RESEARCHERS BUT ALSO ON PEOPLE WHO ARE RECOGNIZED AS POTENTIAL RISING LEADERS. NEXT SLIDE PLEASE. AND THEN FINALLY, THE AAMC HANDS OUT INNOVATION AWARDS, AND THIS YEAR THE CTSA HIT THE TRIFECTA WITH LINDA, SERGIO, AND VINET GETTING FIRST, SECOND, THIRD PLACE AWARDS, IT'S ALWAYS NICE WITH EXTERNAL VALIDATION OF THE CTSAs BEING AT THE FOREFRONT OF INNOVATION. NEXT SLIDE PLEASE. SO THERE'S PROBABLY A LOT MORE BUT I ONLY HAVE SO MUCH TIME. AND CONGRATULATIONS TO ALL OF THESE INDIVIDUALS. THEY REALLY ARE REFLECTIVE OF THE SCOPE AND BREADTH OF THE CTSA. NEXT SLIDE. SO, THE ONE CLOSED SESSION WE HAD WAS FOR R03s, THEY WILL BE AWARDED FY 23 MOVING FORWARD, THIS SHOWS YOU THE FY 22 R03s AND SO THIS IS DIPPING OUR TOE IN THE WATER MOVING INTO AN R PROGRAM, AND THE NICE RANGE OF SPECTRUM OF RESEARCH ACTIVITIES IS VERY, VERY GRATIFYING TO SEE IN THE MORE JUNIOR FACULTY HERE MOVING FORWARD INTO ESTABLISHING THEIR OWN INDEPENDENT RESEARCH PROGRAMS. NEXT SLIDE. THE CCIA AWARDS, FY 22, IT'S A LITTLE THIN BUT I THINK THIS IS PARTLY BECAUSE OF IMPACTS OF COVID IN TERMS OF THE ABILITY OF PEOPLE TO SERIOUSLY PROPOSE DOING SOME MAJOR EFFORTS ALONG THE WAY BUT WE HAVE PROVIDED -- HAVE BEEN ABLE TO AWARD FOUR CCIAs CROSSING THREE DIFFERENT AREAS OF CTSA FOCUS ENGAGING PATIENTS, INNOVATING PROCESSES, AND ADVANCING THE CUTTING EDGE -- USE OF CUTTING EDGE INFORMATICS. NEXT SLIDE. I WANTED TO TALK ABOUT ONE OF THESE. SO THIS IS FROM THE -- THIS IS ACTUALLY CO-FUNDED BY THE NIH OFFICE OF DISEASE PREVENTION, AND IT'S A COLLABORATION AMONG UNC, DUKE, WAKE FOREST, THE THREE CTSAs IN NORTH CAROLINA, LOOKING AT ANALYTICS AND MACHINE LEARNING FOR MATERNAL HEALTH INTERVENTIONS. AS I'VE SAID MANY TIMES IF COVID HADN'T OCCURRED I THINK MATERNITY MORTALITY AND MATERNAL HEALTH WOULD HAVE BEEN A MAJOR FOCUS OF NIH, AND I THINK THERE WILL BE SOME EFFORT TO GET BACK, GETTING BACK INTO THAT. WE'RE SEEING QUITE A BIT OF EFFORT OUT IN THE COMMUNITY, AND THIS IS ONE CCIA THAT WILL BE ABLE TO ACTUALLY INTEGRATE ACROSS THE ENTIRE STATE OF NORTH CAROLINA TO REALLY BE ABLE TO FOCUS ON MACHINE LEARNING CAPABILITIES FOR MOVING THIS FIELD FURTHER FORWARD. NEXT SLIDE. IN TERMS OF THE CONSORTIUM-WIDE ACTIVITIES, R2D2, WE MADE ONE AWARD, TRANSLATING HEALTH INFORMATICS TOOLS TO RESEARCH AND CLINICAL DECISION MAKING, ENACT. THE IDEA IS THIS IS CREATING A FEDERATED SYSTEM THAT IS TRYING TO PROMOTE A USER FRIENDLY COLLABORATIVE RESEARCH AND COMPUTING ENVIRONMENT TAKING INTO CONSIDERATION NATURAL LANGUAGE PROCESSING, AND A PLATFORM FOR STATISTICAL AND MACHINE LEARNING CAPACITY. YOU'LL SEE LATER ON IN A SLIDE, I DON'T THINK FEDERATED VERSUS CENTRALIZED IS AN EITHER/OR DECISION. I THINK WE NEED TO DO BOTH AND THIS IS A VERY GOOD EXAMPLE OF FOCUSED ON LOOKING TO SEE HOW WE CAN PUSH FEDERATED SYSTEMS TO BE MORE USER FRIENDLY IN TERMS OF PENETRATION ACROSS THE RESEARCH COMMUNITY. NEXT SLIDE PLEASE. AND JUST TO HIGHLIGHT SOME OF THOSE SUPPLEMENTS YOU SAW EARLIER THIS MORNING, REALLY ARE PART AND PARCEL OF RECOGNITION BEYOND NCATS. LEFT SIDE YOU SEE COLLABORATION WITH THE VARIOUS COMPONENTS OUTSIDE OF NCATS FROM NIH WHO CAME TO US IN TERMS OF WANTING TO EITHER CO-FUND PROJECTS OR ASK US TO USE FUNDING MECHANISMS TO DELIVER O.D. FUNDS FOR SPECIFIC TYPES OF APPLICATIONS THAT RELATE TO EITHER OBSSR, THE BEHAVIORAL AND SOCIAL SCIENCE RESEARCH, ODSS WHICH IS DATA SCIENCE AND SECURITY TYPE ISSUES. SO, NEXT SLIDE PLEASE. NOW I WANT TO TALK ABOUT SOME OF OUR MOST VALUABLE RESOURCES HERE WHICH IS OUR PEOPLE. SO THE NEXT SLIDE WILL START OUT LOOKING AT SOME OF THE KL 2 SCHOLARS, I'LL TALK ABOUT TWO OF THEM HERE. SO AMIR IS A KL2 SCHOLAR, A PROJECT THAT I THINK REALLY IS AT THE HEART OF NCATS. SO, HIS EFFORTS ARE IN DEVELOPING IMPLANTABLE ULTRASOUND DEVICE FOR SPINAL CORD INJURIES. THE POTENTIAL IS WIDE OPEN. HIS WORK AS A KL2 SCHOLAR LED TO AN AWARD OF OVER $13 MILLION FROM DARPA TO REALLY PUSH THIS FORWARD AND I THINK THIS IS THE KIND OF INNOVATION AND CUTTING EDGE TYPE OF WORK THAT'S REALLY INDICATIVE OF WHAT WE'RE LOOKING FOR IN KL2s. NEXT SLIDE PLEASE. AND THEN LAURA IS FOCUSED ON MULTI-SYSTEM INFLAMMATORY SYNDROME IN CHILDREN. THIS HAS GONE DOWN I THINK PROBABLY AS A CONSEQUENCE OF CHILDREN HAVING SURVIVED COVID, COVID INFECTIONS, AND IMMUNITY PROBABLY BEING A MAJOR SOURCE OF PREVENTION OF FUTURE ISSUES, BUT UNDERSTANDING THIS VERY COMPLEX AND ILL-DEFINED DISEASE ENTITY WHICH IS TERRIFYING NOT ONLY TO PARENTS BUT ALSO TO PHYSICIANS TAKING CARE OF THESE CHILDREN, THERE'S REALLY A LOT OF GAPS IN OUR UNDERSTANDING. AND HER RESEARCH EFFORTS ARE REALLY FOCUSED ON DECIPHERING EXACTLY WHAT THIS MYSTERY SYNDROME IS. THAT'S SOMETHING NIH DOESN'T ALWAYS DO A GOOD JOB UNLESS YOU WIN A NOBEL PRIZE. WITH NIH IT'S WHAT HAVE YOU DONE FOR ME LATELY, BUT WANT TO CHAIR EXAMPLES. COLLEEN WAS A KL2 SCHOLAR NEARLY TEN YEARS AGO, AT THE GEORGIA CTSA, HER FOCUS NOW IS LOOKING AT WASTE WATER SURVEILLANCE FOR SARS. PRE-SARS IF YOU SAID SAMPLING WASTE WATER FOR INFORMATION ON INFECTIOUS DISEASE, YOU WOULD HAVE-LAUGHED OUT OF THE ROOM. WE'VE SEEN HOW VALUABLE THIS CAN BE WITH COVID AND SUBSEQUENT WORK HAS ALSO SHOWN SOME POTENTIAL FOR MONKEYPOX AS WELL AS POLIO. THIS IS A REAL AREA THAT WILL EXPAND IN THE FUTURE AND IS SORT OF ORTHOGONAL APPROACH TO DISEASE SURVEILLANCE THAT PEOPLE WOULD HAVE DISMISSED IF IT HADN'T COME ABOUT BECAUSE OF SARS. NEXT SLIDE. AND RENEE IS A FORMER KL2 SCHOLAR FROM UCSF, FROM ABOUT TEN YEARS AGO ALSO, NOW ASSOCIATE CHAIR FOR HEALTH SERVICES RESEARCH. AND SHE'S ACTUALLY THE FIRST EMERGENCY MEDICINE PHYSICIAN INDUCTED INTO THE AMERICAN SOCIETY FOR CLINICAL INNOVATION. AND YOU MAY HAVE SEEN THIS BECAUSE IT'S GOT RECENTLY -- THIS HAD GOT QUITE A BIT OF PRESS, BUT SHE LED A RETROSPECTIVE STUDY SHOWING HOW RACE, INCOME, AND LOCATION PLAY A ROLE IN WHO GETS THE OPTIMAL TREATMENT WITH REGARD TO STROKE INTERVENTIONS, AND THIS IS SOMETHING WE REALLY -- THIS IS A SOURCE OF DISPARITY WE SEE IN THIS AREA AND SOMETHING HER WORK IS POINTING OUT HOW WE NEED TO GO ABOUT ADDRESSING THIS. NEXT SLIDE PLEASE. SO MOVING OVER TO THE TL1s, THE CURRENT TRAINEE, WE HAVE A LOT OF WORK GOING ON THROUGH "HEAL" LOOKING AT PAIN AND THIS IS ONE EFFORT THAT HE'S DONE AS PART OF HIS TL1 PROJECT LOOKING AT PSYCHOLOGICAL TREATMENT FOR CHRONIC BACK PAIN, SOMETHING NEAR AND DEAR TO MANY OF THE HEARTS OF PEOPLE IN MY CURRENT COHORT. PAIN REPROCESSING THERAPY AS TREATMENT FOR CHRONIC BACK PAIN. THIS WAS PUBLISHED RECENTLY, AND THAT ARTICLE ACTUALLY TOPPED THE LIST OF THE MOST VIEWED PUBLICATIONS IN JAMA PSYCHIATRY, SO A LOT OF INTEREST AND A LOT OF UPTAKE OF THIS. NEXT SLIDE PLEASE. AND THEN IN TERMS OF WHERE ARE THEY KNEW, A FORMER TL 1 FROM CASE WESTERN, CANCER DISPARITIES, WHAT THE EFFECTS OF THAT WAS. HE'S NOW CURRENTLY AN MBA CANDIDATE AT THE KELLOGG SCHOOL OF MANAGEMENT AT NORTHWESTERN UNIVERSITY, AND I THINK THIS IS ONE AREA THAT I FIND ONE ASPECTS THAT I THINK IS WE DON'T OFTEN HIGHLIGHT THIS ENOUGH, PEOPLE WHO COME THROUGH OUR TRAINING PROGRAMS AND THEN GO OFF INTO SLIGHTLY DIFFERENT CAREER TRAJECTORIES, WHAT WE TRADITIONALLY THINK OF IN SOMEONE DOING A TRADITIONAL ACADEMIC MEDICINE TYPE APPOINTMENT BUT I THINK THIS IS VERY -- A VERY VALUABLE RESOURCE THAT WE CAN CAPITALIZE ON LATER ON. NEXT SLIDE PLEASE. AND THEN YOU ALSO HEARD THIS MORNING WITH THE SUPPLEMENTS WE'VE HAD FOR SEVERAL YEARS NOW A VERY PRODUCTIVE CTSA PROGRAM, DIVERSITY AND REENTRY AWARDEES, SIX FOR FY 22 COHORT YOU CAN SEE THIS YEAR. NEXT SLIDE I WANT TO TALK ABOUT A COUPLE OF THESE. CECILIA IS ASSISTANT PROFESSOR OF MEDICINE IN HEMATOLOGY AT YALE, AND HER PROJECT IS USING IMPLEMENTATION SCIENCE METHODS TO PROMOTE INCREASED UPTAKE OF AAP GUIDELINES IN THE CLINICAL PRACTICE. I THINK THIS IS ONE OF THE AREAS THAT WE'RE REALLY DROPPING THE BALL HERE, THAT WE COME OUT WITH GUIDANCE, WITH GUIDELINES, RECOMMENDATIONS, BUT THE INTRODUCTION OF THOSE INTO CLINICAL PRACTICE DOESN'T ALWAYS OCCUR FOR UNCLEAR REASONS, AND I THINK WE DON'T NECESSARILY PUT ENOUGH ATTENTION INTO FOCUSING ON NOT JUST SAYING THIS IS WHAT YOU SHOULD DO BUT ACTUALLY HOW YOU CAN INTEGRATE THAT INTO ROUTINE CLINICAL PRACTICE. FOR THOSE WHO MIGHT BE INTERESTED IN THIS AREA, THERE WAS A RECENT PUBLICATION LOOKING AT THE SUM TOTAL OF ALL OF THE RECOMMENDATIONS IN CLINICAL GUIDANCE INCLUDING WHAT CMS WANTS PHYSICIANS TO DO IN TERMS OF PATIENT EVALUATION. AND CAME TO THE STARTLING CONCLUSION THAT IF A PHYSICIAN WANTED TO SEE THE SAME NUMBER OF PATIENTS PER DAY, BUT INTEGRATE ALL OF THE CURRENT GUIDELINES AND RECOMMENDATIONS THAT ARE OUT THERE, THEY WOULD NEED 26.7 HOURS PER DAY TO DO THAT. SO, WE JUST CAN'T ISSUE GUIDELINES. WE REALLY NEED TO THINK ABOUT -- TAKE IMPLEMENTATION SCIENCE APPROACH TO HOW WE CAN ACTUALLY GET THAT UPTAKE AND NOT THROW A MONKEY WRENCHING INTO JUST ROUTINE CLINICAL CARE. NEXT SLIDE PLEASE. AND THEN JAMEELA, ASSISTANT PROFESSOR OF COMMUNITY HEALTH AT MCW, THAT'S MEDICAL COLLEGE OF WISCONSIN, SHE'S LOOKING AT THE EXTENT TO WHICH COVID-19 HAS AFFECTED FACTORS WITH CHURCH READINESS TO ENGAGE, IN MILWAUKEE THE CTSA THERE MCW HAS A PROMINENT ROLE IN FAITH-BASED COMMUNITIES AND THEY HAVE PUT A TREMENDOUS AMOUNT OF EFFORT IN. COVID UPSET THE ABILITY OF THAT COMMUNITY FAITH-BASED HEALTH PROMOTION EFFORTS THAT THEY'VE HAD, SO SHE'S LOOKING AS TO HOW THEY CAN TAKE THAT INTO ACCOUNT AND RECONCILE THAT WITH THE LONG-TERM GOAL OF GETTING THE CHURCHES INTO A BETTER POSITION TO ENGAGE THEIR MEMBERS FOR HEALTH PROMOTION. NEXT SLIDE PLEASE. AND SO AGAIN WHERE ARE THEY NOW? NATALIE, SHE'S A FORMER DIVERSITY SUPPLEMENT FROM THREE YEARS AGO, SHE'S GONE TO BECOME EXECUTIVE DIRECTOR FOR THE CENTER FOR MATERNAL HEALTH EQUITY AT MOREHOUSE, AND HER FOCUS IS ON MATERNAL MORTALITY AND MORBIDITY PARTICULARLY AMONG BLACK WOMEN IN GEORGIA, IN GENERAL AN AREA THE U.S. IS DOING VERY POORLY IN TERMS OF PEER NATIONS WITH MATERNAL MORTALITY, SOMETHING THAT WE REALLY NEED TO DO A MUCH BETTER JOB, MORE ATTENTION NEEDS TO BE PAID TO THIS. NEXT SLIDE PLEASE. A LITTLE BIT ON N3C, TONE JONI TOUCHED ON A FEW THINGS. I WANT TO -- I'M STILL FLABBERGASTED BY THE EXTENT, WE'RE JUST ABOUT TWO YEARS OLD, WITH N3C, AT THE TIME WHEN WE ESTABLISHED THIS, SET THIS UP, WE THOUGHT WE WOULD DO WELL IF WE HAD SOMEWHERE BETWEEN A QUARTER OF A MILLION AND HALF MILLION COVID PATIENTS. AS YOU CAN SEE, WE'VE JUST GONE OVER 6 MILLION COVID PATIENTS, NUMBERS ARE IMPRESSIVE. AND THE WEALTH OF DATA THAT'S AVAILABLE FOR RESEARCHERS TO LITERALLY ASK ANY TYPE OF QUESTION THEY WANT IS JUST UNPRECEDENTED. NEXT SLIDE PLEASE. SO THERE'S BEEN QUITE AN ARRAY. YOU CAN SEE THE NUMBER OF PUBLICATIONS AND PRE-PRINTS CONTINUES TO REALLY JUST START TO COME OUT. I'LL DRAW YOUR ATTENTION TO TWO PUBLICATIONS, ONE IN THE UPPER LEFT OUT OF THE JOURNAL OF RURAL HEALTH, SO THAT'S A HIGHER HOSPITALIZATION AND MORTALITY RATE AMONG SARS-COV-2-INFECTED PERSONS IN RURAL AMERICA. THIS WAS -- THIS IS POSSIBLE BECAUSE OF THE INVOLVEMENT WITHIN N3C OF NIGMS'S PROGRAM, ALLOWED THIS TO BE DONE, ALMOST IMPOSSIBLE FROM ANY SINGLE INSTITUTIONAL MEDICAL RECORD. BOTTOM LINE COMPARABLE PATIENTS LIVING IN RURAL ENVIRONMENT SUFFERED ABOUT A 30% HIGHER MORTALITY COMPARED TO THEIR COMPARABLE URBAN COMPARISON GROUP. IT'S VERY STRIKING AND I THINK HIGHLIGHTS A MAJOR HEALTH DISPARITY IN THIS COUNTRY OF WHAT IS AVAILABLE IN TERMS OF HEALTH CARE IN THE RURAL ENVIRONMENT VERSUS URBAN ENVIRONMENT. LOWER RIGHT-HAND CORNER, AMONG CHILDREN, AGAIN, CHILDREN HAVE NOT BEEN THE MAJOR PLAYERS IN COVID. THERE IS A VERY STRONG AGE DEPENDENCE. AT ANY INDIVIDUAL INSTITUTION THE NUMBER OF CHILDREN THEY HAVE SEEN HAS NOT BEEN EXTENSIVE ENOUGH TO PROVIDE THESE TYPES OF OVERALL ANALYSES AND SO N3C HAS PERMITTED SOME REALLY GOOD AGGREGATION OF DATA TO PERMIT SUFFICIENT POPULATIONS THAT THE CHARACTERISTICS AND OUTCOMES OF COVID INFECTION IN CHILDREN CAN REALLY BE DELINEATED. NEXT SLIDE PLEASE. AND, YOU KNOW, BEYOND COVID, ONE OF THE THINGS THAT N3C IS PROVIDING US IS THE CAPABILITY OF LOOKING AT A VERY LARGE CENTRALIZED DATABASE. AND THIS IS ONE SUCH PUBLICATION THAT CAME OUT RECENTLY THAT'S LOOKING AT THE SYNERGIES BETWEEN CENTRALIZE AND FEDERATED APPROACHES TO DATA QUALITY, SO AS I SAID EARLIER I DON'T THINK IT'S CENTRALIZED VERSUS FEDERATED AS AN EITHER/OR, THEY BOTH OFFER ATTRACTIVE FEATURES, WE HAVE TO UNDERSTAND LIMITATIONS OF EACH AND WHAT CAN BE DONE MOVING FORWARD, AND N3C OFFERS A GOOD OPPORTUNITY TO IDENTIFY THE CAPABILITIES AND EXTENT OF WHAT CAN BE GOTTEN OUT OF CENTRALIZED DATABASE. NEXT SLIDE PLEASE. AND BEYOND JUST THE SCIENTIFIC AND MEDICAL RESEARCH THAT IS GOING ON, N3C HAS PROVIDED INPUT TO A LOT OF GUIDANCE AND POLICY IMPACTS AND SO HERE ARE JUST FIVE PUBLICATIONS REFERENCED IN 22 POLICY DOCUMENTS, MAJORITY FROM CDC, BUT YOU CAN SEE THIS IS REALLY INTERNATIONAL IN TERMS OF WHO IS READING THESE PAPERS, ALSO IN ADDITION TO THOSE POLICY DOCUMENTES WE HAVE THE WHITE HOUSE, THE ONE JONI CALLED OUT, FROM THE WHITE HOUSE THE FIRST ANNUAL REPORT ON PROGRESS TO IMPLEMENTATION OF THE AMERICAN PANDEMIC PREPAREDNESS PLAN, ALSO INCLUDED A SHOUT OUT TO N3C AS A COMPONENT TO THAT. NEXT SLIDE PLEASE. AND THEN N3C IS GETTING NOTICED BEYOND THE NIH DIRECTOR'S BLOG IN THE UPPER RIGHT. THAT IS THAT FIRST PUBLICATION THAT JONI HIGHLIGHTED. THE NIH DIRECTOR'S OFFICE CALLED THIS OUT IN THEIR BLOG. IT WAS TOTALLY SELF-IDENTIFIED BY THEM AS BEING OF SIGNIFICANCE TO PUT IT IN THE ANNUAL -- MONTHLY DIRECTOR'S BLOG. YOU SEE SOME OTHER MEDIA STORIES THAT HAVE COME OUT REALLY TALKING ABOUT, YOU KNOW, THE POWER OF MACHINE LEARNING REALLY BEING DELVING INTO LONG COVID AND WE THINK THAT THIS IS A KEY FEATURE OF WHAT N3C OFFERS. NEXT SLIDE PLEASE. SO, I'LL TURN TO GENERAL CTSA NEWS, FIRST ABOUT COVID ACTIVITIES, ON THE NEXT SLIDE. JONI MENTIONED PAXLOVID REBOUND, WE'VE DONE ANALYSIS USING N3C. BUT THIS WAS A STUDY THAT CAME OUT ALSO OVER THIS SUMMER WHICH WAS FROM ONE OF OUR CTSA PROGRAMS, CASE WESTERN, THAT LOOKED SPECIFICALLY AT PAXLOVID AND MOLNOPIRAVIR AND LOOKING AT REBOUND PRETTY MUCH CAME TO SIMILAR CONCLUSIONS USING A SLIGHTLY DIFFERENT DATASET. BUT THE FOCUS IS CLEARLY THERE WAS A LOT OF CONCERN THAT THIS WAS GOING TO BE AN ISSUE. I THINK BOTH THIS PUBLICATION AND THE N3C ANALYSIS WE DID REALLY SHOWED THAT WHILE IT IS AN ISSUE, IT IS NOT SOMETHING THAT WAS GOING TO IMPACT THE USE OF PAXLOVID IN TERMS OF NEEDING TO ADDRESS IT IN A DIFFERENT WAY. NEXT SLIDE PLEASE. THIS IS A STUDY THAT REALLY DEMONSTRATES THE UTILITY OF THE CTSAs, PARTICULARLY WHEN THEY ARE THE MAJOR CTSA IN THEIR STATE. THIS IS FROM THE INDIANA CTSA, AND THIS IS A STATEWIDE STUDY SHOWING INTERESTING DATA. THAT WAS LOOKING AT SEROLOGY, SHOWING THAT THE ANTIBODY LEVELS WANE OVER TIME. WE'VE KNOWN THAT. BUT IN FACT THEY WANE SLOWER IN CHILDREN. AND IT WAS ABLE TO COLLECT STATEWIDE BIOBANK SAMPLES THAT ALLOWED THIS TO BE DONE AT A STATEWIDE LEVEL. AND THE CTSA WAS INSTRUMENTAL IN BEING ABLE TO COORDINATE WHAT AMOUNTED TO A STATEWIDE EFFORT. NEXT SLIDE PLEASE. AND THEN REAL WORLD EVIDENCE, SO I MENTIONED THIS, I THINK IN A PREVIOUS TALK, BUT WE WERE ASKED -- PROVIDED FUNDING BY OPERATION WARP SPEED TO LOOK AT REAL WORLD EVIDENCE OF MONOCLONALS, KEEPING IN MIND THE FDA REALLY PROVIDED THESE WITH EMERGENCY USE AUTHORIZATIONS ON RELATIVELY LIMITED DATA. AND WHAT THE COLORADO GROUP HAS BEEN ABLE TO DO IS COORDINATE BECAUSE THESE ARE GIVEN AS OUTPATIENTS, COORDINATE STATEWIDE DATA TO FOLLOW PATIENTS WHO RECEIVED MONOCLONAL ANTIBODIES, AND DEMONSTRATED THAT IN GENERAL THE REAL WORLD EVIDENCE SUPPORTED THE CLINICAL TRIAL, LIMITED CLINICAL TRIAL DATA THAT HAS BEEN ACCUMULATED BUT ALSO FOUND ADDITIONAL INTERESTING TID-BITS, SO IN THE CASE OF NEUTRALIZING MONOCLONALS IN THE PRE-OMICRON AREA WHICH THEY HAD MUCH MORE HEAVY UTILIZATION, THEY WERE ABLE TO CONFIRM THERE WAS A 50% REDUCTION IN HOSPITALIZATION BUT INTERESTINGLY ENOUGH 50% WHO DID GET HOSPITALIZED AFTER GETTING A MONOCLONAL THAT POPULATION HAD 90% REDUCTION IN GOING TO THE ICU, SO EVEN IF THE MONOCLONAL DIDN'T KEEP YOU OUT OF THE HOSPITAL IT DID A VERY GOOD JOB KEEPING YOU OUT OF THE ICU. SO THAT WAS NOT PREACHED AT THE TIME BECAUSE OF THE SMALL NUMBERS THAT GOT HOSPITALIZED FROM TREATMENT ORIGINALLY. ACTIVITY IN THE OMICRON UNFORTUNATELY EFFECTIVENESS OF SOTROVIMAB HAS GONE DOWN EVEN WITH IN VITRO ACTIVITY, DOESN'T TRANSLATE INTO CLINICAL EFFICACY. RECENTLY SUBMITTED A STUDY LOOKING AT PAXLOVID, INTEGRATING INFORMATION DATA FROM ACROSS AN ENTIRE STATE WITH MANY DATA SOURCES WILL CONTINUE TO YIELD A LOT OF VALUABLE REAL WORLD EVIDENCE AND POTENTIALLY IF WE WERE TO OBTAIN ADDITIONAL FUNDING COULD BE EXPANDED TO OTHER STATES BECAUSE NOW WE KNOW HOW TO DO THIS. NEXT SLIDE PLEASE. FROM DESCRIPTION, ERIC TOPOL TALKING ABOUT SMARTPHONE APPS, PANDEMIC DRIVING INNOVATION, MAKING MOBILE APPS MORE VIABLE, NOT ONLY A TREMENDOUS IMPACT IN FUTURE PANDEMICS, AND THERE WILL BE FUTURE PANDEMICS, NO WAY TO AVOID THIS, BUT THIS WILL EXPAND THE CAPABILITY AND UTILITY OF APPS FOR GENERAL CLINICAL RESEARCH THAT WILL ALLOW US TO MOVE TO MORE DECENTRALIZED CLINICAL TRIAL CAPABILITIES GOING FORWARD. I THINK THE APPLICATIONS IS ONLY LIMITED CURRENTLY BY OUR IMAGINATION. WE DO STUFF NON-COVID, I'LL HIGHLIGHT BEFORE I FINISH UP. IN THE CASE OF ASTHMA, INTERESTING STUDY THAT WAS JUST PUBLISHED LAST MONTH, THAT WAS LOOKING AT URBAN CHILDREN WITH EXACERBATION-PRONE EOSINOPHILIC ASTHMA IN THE U.S. AND THIS MONOCLONAL ANTIBODY ACTUALLY DECREASED ASTHMA ATTACKS BY 27%, SPECIFICALLY IN BLACK AND HISPANIC CHILDREN AND ADOLESCENTS IN LOW INCOME URBAN NEIGHBORHOODS. A KEY STUDY BECAUSE THIS IS A POPULATION CLEARLY AT HIGH RISK FOR SEVERE ASTHMA DISEASE. CTSA AWARDS REALLY SUPPORTED THE STUDY SITES THAT ARE PART OF WHAT WAS THE CAUSE NETWORK FORMERLY INNER CITY ASTHMA CONSORTIUM TO REALLY ENABLE THIS TRIAL TO BE UNDERTAKEN AND COMPLETED. NEXT SLIDE PLEASE. AND THIS IS AN INTERESTING LITTLE VIGNETTE HERE TRANSLATIONAL THERAPEUTICS ACCELERATOR PILOT AWARDEE. THIS IS FROM COLUMBIA, A PILOT PROJECT, USING ENGINEERED EXOSOMES FOR GENOME EDITING OF LUNG CANCER THERAPIES, ONE OF FOUR SELECTED TO RECEIVE ADDITIONAL FUNDING BY THE AACR-BAYER INNOVATION AND DISCOVERY GRANT, HIGHLIGHTING ABILITY OF THE PILOT PROGRAM, CTSA RUNS, TO REALLY TARGET HIGH IMPACT, HIGH RISK, HIGH REWARD TIMES OF EFFORTS, AND IT'S THE KIND OF THING WE LOOK FORWARD TO WITH THE PILOT PROGRAM. NEXT SLIDE PLEASE. THIS IS AN INTERESTING LITTLE ACCOMPLISHMENT FROM ARKANSAS. IT'S AN INTERACTIVE VIDEO APP FOR ADOLESCENTS FOCUSED ON OPIOID MISUSE. KIDS LOVE VIDEO GAMES, ACTUALLY A LOT OF ADULTS LIKE VIDEO GAMES AS WELL. AND SO THEY DEVELOPED A VIDEO GAME WHERE YOU CHOOSE AN ADVENTURE, AND YOU GET -- MAKE DECISIONS IN THE GAME THAT LEAD TO DIFFERENT OUTCOMES RELATED TO DIFFERENT OPIOID ABUSE SCENARIOS. SO THE KIDS ACTUALLY GET A SORT OF SENSE OF WHAT THIS WOULD BE LOOK. INTERESTINGLY ENOUGH, FOR THOSE WHO ARE FAMILIAR WITH THE NETFLIX BLACK MIRROR EPISODE, APPARENTLY THAT WAS THE INSPIRATION FOR THIS VIDEO APP. SO YOU NEVER KNOW WHERE THE NEXT GREAT IDEA IS COMING FROM. NEXT SLIDE PLEASE. AND THEN THIS ONE YOU'VE HEARD VERY RECENTLY. WE'VE SEEN A LOT OF MEDIA ATTENTION GIVEN TO PULSE OXIMETERS. GEORGIA WAS RESPONSIBLE FOR THE DISCREPANCY, AND THEN STRATIFIED THAT WITH RACE AND ETHNICITY, AND LOOKED AT ASSOCIATION OF THOSE DISCREPANCIES WITH ASSOCIATION WITH ORGAN DYSFUNCTION AND MORTALITY. PULSE OXIMETRY IS NOT GOOD IN GENERAL BUT FOR PARTICULAR INDIVIDUALS WITH -- IN TERMS OF, YOU KNOW, ALONG FITZPATRICK PIGMENTATION SCALE CAN BE WAY, WAY OFF, AND SO I THINK THERE'S STILL SOME EFFORTS, WE'VE HAD SOME DISCUSSIONS WITH CTSA ABOUT THIS. THIS IS AN AREA I THINK WE REALLY NEED TO PUT MORE EMPHASIS AND FOCUS ON, WHETHER THIS IS A HARDWARE SENSOR ISSUE IN TERMS OF SENSITIVITY OR WHETHER THIS IS A SOFTWARE ISSUE IN TERMS OF EVALUATING ACROSS SIGNIFICANT NUMBER, SPECTRUM OF FITZPATRICK SKIN TYPES REMAINS TO BE SEEN BUT I THINK THIS IS AN AREA THAT WE NEED TO PUT SOME EFFORT INTO BECAUSE THESE TYPES OF DEVICES ARE IN FREQUENT COMMON USE AND WE NEED TO MAKE THEM WORK FOR EVERYONE. AND SO THIS WILL BE AN EFFORT OF THE CTSA PROGRAM GOING FORWARD. NEXT SLIDE PLEASE. AND THEN FINALLY, THIS WAS ONE THAT CAUGHT MY EYE. THIS IS FROM UCSD. THIS IS LOOKING AT THE GUT MICROBIOME. IT WAS A PROOF-OF-CONCEPT STUDY. SO WHILE WE CAN DO LOTS OF ELEGANT GENETIC ENGINEERING IN E. COLI, THAT WE'VE BEEN ABLE TO DO FOR SEVERAL DECADES NOW, BUT THOSE ARE WITH LABORATORY STRAINS. AND IN GENERAL, WHEN YOU TAKE AN E. COLI STRAIN OUT OF SOMEONE'S GUT, FIRST OF ALL DOING THE TRANSGENE DELIVERY IS NOT NECESSARILY STRAIGHTFORWARD IN FREE LIVING OR FREE RANGING E. COLI, AND SECONDLY, GETTING THAT TO BE STABLE AND PERSISTENT, YOU KNOW, STABILIZED IN THAT E. COLI AND REESTABLISHING THAT IS NOT STRAIGHTFORWARD. THEY DEVELOPED A SYSTEM THAT DOES ALLOW FOR INTESTINAL TRANSGENE DELIVERY USING NATIVE E. COLI CHASSIS. WHAT THEY ARE ABLE TO SHOW IN MICE IS THEY COULD ACTUALLY CREATE PERSISTENT PHYSIOLOGICAL CHANGES, I THINK THIS OPENS UP THE DOOR FOR POTENTIALLY VERY NOVEL WAYS OF DELIVERING THERAPEUTICS AND MODIFIERS THROUGH INTESTINAL E. COLI THAT WOULD BE ABLE TO COLONIZE AND PROVIDE SOME LONGER-TERM THERAPEUTIC EFFECT, AND I THINK IT REALLY OPENS THE DOOR TO A LOT OF DIFFERENT THINKING ABOUT THE WAY WE APPROACH DISEASES. NEXT SLIDE PLEASE. TO FINISH ON CTSA IMPACT BEYOND SCIENTIFIC AND MEDICAL COMMUNITY I THINK WE DON'T ALWAYS PUT A LOT OF FOCUS ON POLICY, CLINICAL GUIDANCE AND WORK FORCE. YOU CAN SEE WHAT YOU HAVE HERE IS YOU HAVE CDC GUIDANCE DOCUMENTS THAT HAVE BEEN RELEASED OVER THE PAST YEAR. AND OVER TOP YOU CAN SEE THE PUBLICATIONS COMING FROM THE CTSAs THAT HAVE INFORMED THESE DOCUMENTS. SO THE WORK COMING OUT OF THE CTSA IS HAVING AN IMPACT BEYOND SIMPLY THE PUBLICATIONS THEMSELVES, BUT IS ACTUALLY BEING UTILIZED BY THE CDC TO INFORM RECOMMENDATIONS AND GUIDANCE GOING FORWARD. NEXT SLIDE PLEASE. THE WORLD HEALTH ORGANIZATION IS PAYING ATTENTION TO WHAT THE CTSAs ARE DOING, THESE ARE EXAMPLES OF LO WORLD HEALTH ORGANIZATION DOCUMENTS REFERENCING STUDIES FROM CTSA IN TERMS OF IMPACTING AND INFLUENCING THEIR GUIDANCE AND RECOMMENDATIONS. NEXT SLIDE. AND THEN I'M GOING TO FINISH UP, SO I THINK ONE OF THE AREAS THAT I THINK WE REALLY PUT A LOT OF EFFORT AND TALK ABOUT FUTURE WORKFORCE, WE ALMOST EXCLUSIVELY FOCUS ON EITHER OUR TL 1s THAT PRE-DOCS AND POSTDOCS, AND TALK ABOUT JUNIOR FACULTY, BUT I'M REALLY LOOKING FORWARD TO IN THE NEW FOA, R25 SHOULD ALLOW TO GET TO DIFFERENT POPULATIONS, I WANT TO HIGHLIGHT A PROGRAM GOING ON SINCE 2016 AT MEDICAL COLLEGE OF WISCONSIN, CTSA 500 STARS INITIATIVE, ENVISIONED IN 2016 REALLY DOING COMMUNITY ENGAGEMENT TO FOCUS ON THE TRANSLATIONAL WORKFORCE DEVELOPMENT FOR THE FUTURE, WITH THEIR VISION OF ENRICHING SOUTHEAST WISCONSIN WHERE MILWAUKEE IS THROUGH PROMOTING DIVERSITY, INCLUSION, ACCESS TO UNDERREPRESENTED MINORITY AND UNDERPRIVILEGED STUDENTS IN THE AREA, TO BRING ON 50 STUDENTS A YEAR FROM HIGH SCHOOL AND COLLEGE AND PUT THEM INTO ALL DIFFERENT ASPECTS, WHATEVER THEIR INTERESTS HAPPEN TO BE IN TERMS OF CLINICAL AND TRANSLATIONAL RESEARCH OPPORTUNITIES. AND IT'S BEEN WILDLY SUCCESSFUL, OBVIOUSLY IMPACTED BY COVID UNFORTUNATELY, WHICH HAS HAD A LOT OF IMPACT, BUT THEY STILL HAVE BEEN VERY PRODUCTIVE, AND ON THE NEXT SLIDE JUST TO HIGHLIGHT ONE INDIVIDUAL, HARRY IS ONE OF THE 500 STARS. HE WAS AN UNDERGRADUATE IN SCIENCE AT LAWRENCE UNIVERSITY, NOW CURRENTLY A MEDICAL STUDENT AT MCW, IN THE STARS PROGRAM, FOR TWO YEARS, IN THE SUMMER BASICALLY IN 2017 AND 2018, FOLLOWED THAT UP WITH SUMMER PROGRAM FOR UNDERGRADUATE RESEARCHERS, ANOTHER PROGRAM THEY MAINTAINED. BUT SINCE THEN WHAT HE'S DONE IS SOMEWHAT QUITE AMAZING. IF YOU CLICK ONCE, HE'S BEEN NOW NAMED -- HE WAS NAMED -- RECEIVED WISCONSIN INNOVATION UNDER 25 AWARD, HIGHLIGHTED FOR WHAT HE'S DONE, WHICH IS QUITE IMPRESSIVE BECAUSE IF YOU CLICK ONE MORE TIME, HE WENT ON TO BECOME A FELLOW AT NASA'S INTERNATIONAL SPACE STATION, NATIONAL LAB. I DON'T KNOW WHERE THAT IS. BUT HE CERTAINLY MOVED ON INTO THAT. BUT THEN NOW HE'S ACTUALLY TAKEN A SABBATICAL FOR MEDICAL SCHOOL. CLICK ONE MORE TIME. BECAUSE HE'S ACTUALLY STARTED A COMPANY THAT IS TAKING ADVANTAGE OF THE NSF I-CORE, DESCRIBED AS A SCIENTIFIC MASHUP OF AMAZON AND BNB, HE'S TAKEN A YEAR OFF MEDICAL SCHOOL TO WORK, CO-FOUNDED THE COMPANY WITH HIS BROTHER, AND THEY ARE MOVING FORWARD. SO I THINK IT'S THE KIND OF OPPORTUNITIES THAT THE CTSA CAN REALLY CREATE FOR PEOPLE THAT ALLOWS THEM TO DO THINGS THAT IN NORMAL CIRCUMSTANCES THEY WOULD NEVER -- IT WOULD NEVER BE POSSIBLE FOR THEM. THAT'S MY LAST SLIDE. AND HAPPY TO TAKE QUESTIONS. I SEE MATHIAS HAS A HAND UP. . >> YOU SHOULD SEE A LOUD APPLAUSE FROM ALL OF US. >> OIL >> I'M SORRY? >> YOU SHOULD SEE LOUD APPLAUSE. SERIOUSLY, WHAT CTSA, NCATS, YOUR TEAM AND CTSAs ACROSS THE NATION HAVE, YOU KNOW, DELIVERED IS CLOSE TO A MIRACLE. IT'S REALLY IMPRESSIVE. BEFORE COVID, WE HAVE DISCUSSED WITH NCATS LEADERSHIP WE'RE IN NEED OF INFORMATION FRAMEWORK WHO IS TRULY NATIONAL, THIS IS ONE OF THE MAIN DISADVANTAGES OF THE UNITED STATES COMPARED TO (INDISCERNIBLE) AND YOU'VE GENERATED THAT. WITH N3C YOU CAPTURE INFORMATION FROM A LARGE SWATH OF THE POPULATION, DRIVEN BY NATIONAL URGENCY. I THINK WHILE, A, WE HAVE TO DELIVER TO THE ONGOING COVID CHALLENGES, AS WE SEE THEM EVOLVE, THE MAIN OPPORTUNITIES AND YOU'VE BEEN ALLUDING THROUGHOUT YOUR TALK REALLY WANT TO REINFORCE THAT AND JONI, A COMMENT TO YOUR PRESENTATION, TO TAKE THAT ABOVE AND BEYOND COVID, BEYOND CTSA, THIS IS A NATIONAL NEED WE HAVE. AND FROM THAT VANTAGE POINT, 2.8% INCREASE IN BUDGET IS NOT JUSTIFIED, YOU'VE ESTABLISHED A INFRASTRUCTURE THAT'S A CRITICAL RESOURCE FOR UPCOMING PANDEMIC AND ENDEMICS. PLEASE SYSTEMATICALLY ANALYZE WHICH DATASET CAN DO THAT, MY RESEARCH TEAM IS DOING THAT RIGHT NOW, MAKE SURE WITH SUSTAINABILITY, STRATEGIC EFFORTS IN PLACE TO SCALE THAT UP. THIS IS REALLY AN ASPECT WHERE MAKING SURE TO RESOURCE THESE ACTIVITIES GOING FORWARD, THIS IS ONE OF THE KEY ASPECTS TO CLOSE A CRITICAL GAP WE HAVE IN OUR RESEARCH AND HEALTH CARE DELIVERY ENTERPRISE, THERE WILL BE MORE TO TALK ABOUT. ANOTHER PIECE WHICH IS EMERGING BETWEEN THE LINE AND PEOPLE YOU SHOWCASE IS AS A NATION WE HAVE FAILED. WE HAVE FAILED TO PROTECT OUR PEOPLE FROM COVID. AND FROM MY COLLEAGUES IN EUROPE, I STILL HEAR LOUD AND CLEAR UTTER MISUNDERSTANDING WITH A NATION WITH THE WORLD'S BEST EPIDEMIOLOGISTS AND DATABASES AND SYSTEMS, WHY ARE WE NOT ABLE TO PENETRATE OUR COMMUNITY, CLEARLY A WAVE OF MISINFORMATION IN THE HEALTHCARE DOMAIN HAS RESULTED IN THE REALITIES WE'RE FINDING OURSELVES IN. AND THAT LEADS IMMEDIATELY TO THE NEXT EFFORT YOU HAVE, INITIATED AND RIGOROUSLY PRESENTED TODAY WE HAVE TO GET OUR INFORMATION BACK AND DOING THAT IN THE AREAS OF THE POPULATION WHERE THAT MISINFORMATION IS RAMPANT IS CRITICAL. EFFORTS YOU'VE SHOWN ARE STEPS IN THE RIGHT DIRECTION. SYSTEMATICALLY EDUCATING A WORKFORCE ACROSS THE MINORITY, SOCIOECONOMIC, RURAL COMMUNITY WHERE WE HAVE VERY POOR PENETRATION IS ANOTHER CRITICAL ASPECT AND AGAIN CRITICAL POINT FOR NCATS TO MAKE TO LEADERSHIP POSITION, GOING FORWARD, CLEARLY WE CANNOT DO THAT IN THE FRAMEWORK OF CTSA AND NCATS STILL REMAIN AS KEY OPINION LEADERS TO COUNTERACT THAT AND MANY PROFESSIONALS SOCIETIES ARE REACHING OUT TO MEMBERSHIPS TO HELP US TO ADDRESS THE MISINFORMATION WAVE WHO KILLED SO MANY PEOPLE EVERY DAY AND PREDICTION IS THAT IT WILL ESCALATE AND NOT GO DOWN SO FINDING STRATEGY, DEVELOPMENT, WE HAVE ALSO TOOLS IN HAND TO DO THAT, YOU DON'T HAVE THE RESOURCES AND PROBABLY NOT EVEN MANDATE BUT USING THAT AS AN EXAMPLE HOW WE AS A MEDICAL SOCIETY CAN ADDRESS MISINFORMATION PANDEMIC I THINK MIGHT BE THE PRESENTATIONS. >> THANK YOU, MATHIAS. YEAH, A LOT TO UNPACK THERE. BUT I CERTAINLY AGREE WITH YOU THAT, YOU KNOW, WE'RE STARTING FROM A SITUATION OF WHERE OUR HEALTHCARE SYSTEM IS PHENOMENALLY VULCANIZED IN THE U.S. TWO HOSPITALS ACROSS THE STREET FROM EACH OTHER BOTH USING EPIC CAN'T TALK TO ONE ANOTHER. THAT WAS ONE OF THE INITIAL FOCUSES OF CD2H FIVE YEARS AGO WAS INTEROPERABILITY OF DATA, THAT WORK DONE PRE-COVID WORKING ON THAT WHICH WAS, YOU KNOW, I'LL USE THE TERM THAT KEN USED, DIRECTOR OF INFORMATICS, IT'S PLUMBING. IT'S NOT SEXY. IT'S NOT EXCITING KINDS OF THINGS BUT IT'S GRUNT WORK TO WORK ON THAT INTEROPERABILITY AND THE NOTION THAT SOMEHOW WE COULD CAJOLE EVERYONE TO USE -- DO EVERYTHING THE VERY SAME WAY SO WE WOULD HAVE INTEROPERABILITY BECAUSE EVERYBODY WOULD BE DOING IT ALL THE SAME WAY, DEFINING DATA ELEMENTS EXACTLY, IS NEVER GOING TO HAPPEN. SO WHAT WE BROUGHT TO BEAR WAS A TECHNOLOGIC SOLUTION SO PEOPLE DON'T HAVE TO CHANGE THE WAY WE'RE DOING SOMETHING, WE CAN TAKE WHAT YOU'RE DOING AND WHAT SOMEBODY ELSE IS DOING, I'M LOOKING AT YOU ON MY SCREEN, MOO OF MATHIAS AND ANNIE, EACH DOING IT YOUR OWN WAY, BUT WE HAVE THE WAY TO BRING IT TOGETHER TO ACTUALLY BE USED. THAT'S AN IMPEDIMENT TO A RESEARCHER IF THEY ARE GOING TO SPEND THE FIRST HALF OF THEIR GRANT PERIOD JUST FIGURING OUT HOW TO GET DATA INTEROPERABILITY TO WORK SO THEY CAN THEN ADDRESS THE QUESTION. WE'VE SORT OF CRACKED THAT NUT. I THINK WE UNDERSTAND HOW TO DO THAT AND SO WE CAN EXPAND BEYOND COVID AND GETTING TO KELLY'S QUESTION IN THE NOTE, THE SUSTAINABILITY IS AN ISSUE WITH THIS SORT OF THING BECAUSE OF THE AMOUNT OF FUNDING THAT IS REQUIRED TO MAINTAIN IT. COVID SORT OF, YOU KNOW, CLEARED THE TABLE THAT IT WAS AN ALL-HANDS-ON-DECK KIND OF THING AND A LOT OF THE COMMUNITY REALLY JUST OFFERED THEIR TIME AND SWEAT EQUITY IN TERMS OF PULLING THIS OFF. BUT I THINK YOU CORRECTLY, YOU KNOW, CORRECTLY SURMISED THAT THE APPLICABILITY FOR SOMETHING LIKE, FOR EXAMPLE, MATERNAL MORTALITY SHOULD NOT BE LOST. ANY GIVEN HOSPITAL IS JUST NEVER GOING TO HAVE ENOUGH PREGNANT WOMEN DYING THAT THEY ARE GOING TO BE ABLE TO REALLY MAKE SENSE OF THAT. THIS REQUIRES A NATIONAL COORDINATION IN TERMS OF UNDERSTANDING THIS. SO I THINK THERE'S THE SAME THING THAT COULD BE SAID FOR RARE DISEASES IN THE SAME WAY, TO BE ABLE TO HAVE A VERY EFFICIENT WAY TO AGGREGATE AND ORGANIZE AND COORDINATE DATA AND MAKE THAT AVAILABLE TO THE RESEARCH COMMUNITY IS SOMETHING THAT WE'RE REALLY EXAMINING CLOSELY AND LOOKING AT WAYS WE CAN CONTINUE THIS EFFORT AND PERPETUATE THIS EFFORT IN OTHER SCIENTIFIC AND MEDICAL AREAS. >> AND I COULDN'T AGREE MORE. THANKS FOR YOUR COMMENTS, MATHIAS. TO WHAT MIKE SAID, I WANT TO ADD THE IDEA THAT ESSENTIALLY THE BIGGEST PROBLEM WE HAD GOING INTO THE PANDEMIC WAS THAT WE DIDN'T COMMUNICATE ELECTRONICALLY AND COULDN'T UNDERSTAND WHAT OUR ELECTRONIC HEALTH RECORDS WERE SAYING TO US AT THAT LEVEL, N3C SOLVED THAT PROBLEM. THIS HAS BEEN THIS COORDINATION THIS AMAZING RESEARCH COMMUNITY FROM THIS CTSA GROUP, FROM THE NIGMS IDEA STATE CTR GROUP HAS BEEN AN AMAZING LEADER IN THIS SPACE TOO. AND AS WELL AS OTHER PARTNERS ALONG THE WAY WHO HELPED DRIVE THIS IDEA OF INTEROPERABILITY. SO WHEN MIKE SAYS HE SEES MATHIAS AND AMY ON THE SCREEN TOGETHER, THEY ARE ON DIFFERENT CORNERS HOW I SEE THEM, SO WE'RE ABLE TO FIGURE OUT HOW TO DO ZOOM AND BRING THESE DIFFERENT PICTURES TOGETHER ON OUR SCREENS BUT WHEN IT COMES TO THOSE DATA IT'S SO IMPORTANT THAT WE ALSO BE ABLE TO COMMUNICATE BACK TO THE DATA PROVIDERS THAT WHAT THEY ARE GIVING US IS IN A DIFFERENT FORMAT AND WE CAN GIVE THEM BACK THE ABILITY TO MAP ON THEIR DATA ONTO DIFFERENT FORMATS SO THEY CAN CONTINUE TO WORK WITH OTHER DATA SYSTEMS AS WELL. SO IT'S REALLY ENABLING THE ENTIRE ECOSYSTEM TO BE ABLE TO DO THESE TRANSFORMED LOADS OF DATA AND INFORMATION MUCH MORE READILY AND I THINK THIS IS JUST A KEY CONTRIBUTION THAT N3C HAS MADE THAT I DON'T KNOW IF ANDREW CAN FIGURE OUT HOW BIG THAT CONTRIBUTION REALLY IS. IT'S GOING TO BE A TOUGH ONE. BUT I THINK IT'S BEEN REALLY POWERFUL FOR THE RESEARCH COMMUNITY TO NOW BE ABLE TO HAVE THIS. AND AS MIKE MENTIONED TOO, IMPORTANTLY FOR MATERNAL MORBIDITY AND MATERNAL HEALTH VERY CRITICAL FOR RARE DISEASES, GOSH, THEY ARE NEARLY INVISIBLE IN THE ELECTRONIC HEALTH RECORD SYSTEM. THE MORE WE CAN USE THESE DATA AND START TO INCORPORATE I.C. CODES THAT ARE MORE MEANINGFUL OR SNOMED TERMS OR PHENOTYPIC DATA AS PROXIES UNTIL WE GET THAT OTHER WORK FIGURED OUT, WE'RE NOT ABOUT BILLING, WE'RE ABOUT RESEARCH AND UNDERSTANDING HOW WE CAN MOVE FORWARD IN THE RARE DISEASE SPACE. SO I THINK THERE'S HUGE CONTRIBUTIONS LEFT TO BE SEEN HERE. AND I'M REALLY EXCITED ABOUT THAT. SO IT'S DEFINITELY ONE OF THOSE THINGS THAT IS -- I THINK A NO-BRAINER FOR US AND WE'RE GOING TO CONTINUE TO WORK ON HOW WE CAN BEST ENGAGE IN IDEAS OF BRINGING THAT SUPPORT IN TO HELP US ENABLE THAT. MARSHALL, AND I THINK I HEARD KELLY BUT I'M NOT SURE IF IT WAS KELLY. MARSHALL, I SEE YOUR HAND. >> KIND OF JUST PILING ON TO WHAT YOU JUST SAID ONE OF THE THE DREAMS IN RARE DISEASE HAS BEEN ABLE TO DO NATURAL HISTORY STUDIES AND PREVALENCE AND THINGS LIKE THAT FROM THE EHR WHICH WE REALLY HAVE NOT BEEN ABLE TO DO. I'M KIND OF HOPING THAT SOME OF THE TOOLS AND SOME OF THE THINGS YOU'VE LEARNED HOW TO DO FROM THIS CAN BE APPLIED. THAT WOULD BE INCREDIBLY STRONG. >> YEAH, MARSHALL, IT'S ONE OF THESE THINGS THAT DOESN'T SOUND, AGAIN, EXCITING FROM AN N3C STANDPOINT BUT ONE OF THE IMPEDIMENTS FOR INTEROPERABILITY IS DIFFERENT HOSPITALS WILL NAME THINGS AND CODE THINGS DIFFERENT WAYS. >> OH, YEAH. >> YOU DON'T KNOW THAT WHEN THEY SAY X AND SOMEBODY ELSE SAYS X THEY ARE TALKING ABOUT THE SAME THING. AND SO ONE OF THE -- YOU KNOW, THERE'S A MAJOR EFFORT AND, AGAIN, THIS WAS ALL SORT OF ORGANIC, WAS THESE CLINICAL DOMAIN TEAMS THAT SAT DOWN TO SAY IF WE'RE GOING TO TALK ABOUT SOMETHING LIKE DIABETES LET'S STANDARDIZE DIABETES IN TERMS OF HOW THAT APPEARS IN THE EHR, THERE'S DOZENS AND DOZENS OF THESE, SOUNDS TRIVIAL BUT THERE'S -- >> NO, IT'S NOT. >> IT'S NOT. IT'S NOT. BUT YOU WOULD THINK -- SO THERE IS ACTUALLY SOME WORK, I'M RELUCTANT BECAUSE OF THE POST-ROE DECISION TO TALK ABOUT VERY MUCH, BUT YOU CAN'T ALWAYS TELL FROM THE EHR WHO IS PREGNANT. >> I WAS PART OF A PROJECT AT VANDERBILT STARTING TO DO EARLY MINING, VISUAL HEALTH RECORDS, LIKE YOU SAID DIABETES, IT'S CALLED 20 THINGS. I DID A PROJECT, LOOKED TO SEE HOW MANY THINGS DOWN SYNDROME WAS CALLED. >> RIGHT. >> EHR AND CHILDREN'S HOSPITAL. I IDENTIFIED OVER 20 DIFFERENT WAYS OF CALLING IT DOWN SYNDROME. AND SOME YOU MIGHT PULL UP ON SEARCHES, SOME YOU MIGHT NOT. >> RIGHT. AND SO THE CLINICAL DOMAIN TEAMS OF WHICH WE HAVE OVER 30 HAVE TAKEN ON THE WORK OF STANDARDIZING SO THAT WHEN THESE DIFFERENT TERMINOLOGIES COME IN, DIFFERENT EHR TERMS COME IN, THEY CAN BE MAPPED APPROPRIATELY SO YOU GET THAT INTEROPERABILITY. IT'S A TREATMENT LIFT BUT ALL OF THAT EFFORT HAS BEEN -- IT'S ALL AVAILABLE IN SOME SPACE, YOU KNOW, THE I.T. PEOPLE, I.T. GURUS, GITHUB AND THAT SORT OF THING KNOW WHERE TO GO TO FIND IT. SO THAT PEOPLE DON'T HAVE TO REINVENT THE WHEEL, MORE IMPORTANTLY THEY DON'T REINVENT THE WHEEL THREE WAYS. >> THE HPO PROJECT, ONTOLOGY PROJECT. >> EXACTLY. EVEN IF EVERYBODY'S REINVENTING THE WHEEL, THEN THE QUESTION IS, IS THEIR WHEEL THE SAME AS MY WHEEL? AND SO I THINK THIS WILL GO A LONG WAY IN TERMS OF INVIGORATING THE INTEROPERABILITY ASPECT OF FUTURE STUDIES. BEYOND COVID. ANNIE? >> I JUST HAVE A QUESTION ABOUT WHAT HAPPENS DOWNSTREAM WITH SOME OF YOUR FINDINGS FROM THIS PROJECT BECAUSE I THINK, I MEAN, AS OTHERS HERE KNOW WELL ONE OF OUR BARRIERS IN RARE DISEASE IS THAT WE DON'T HAVE ICD CODES FOR MAJORITY OF RARE DISEASES. AND SO ONE OF THE BARRIERS WHEN DOING WORK LIKE YOU'RE TALKING ABOUT ARE PEOPLE WITH RARE DISEASES ARE INVISIBLE WHEN YOU'RE LOOKING THROUGH CODES AND LOOKING AT EHR DATA. I GUESS ONE OF THE THINGS THAT WOULD BE REALLY INTERESTING IS AS YOU'RE BUILDING THIS TAXONOMY OR IDENTIFYING, LOOKING THROUGH DATASETS AND YOU'RE LOOKING AT THIS PARTICULAR DISORDER, ESPECIALLY THE MORE ULTRA RARE DISEASES, IS CALLED THIS OVER AND OVER AGAIN, AND YOU CREATE A METHODOLOGY OR ALGORITHM FOR THAT, IS THERE A PLAN FOR HOW THAT GETS RELAYED BACK TO WHETHER IT'S THE CENTER FOR HEALTH STATISTICS OR IS THERE AN INTERAGENCY WORKING TOGETHER? IT DOES HARM THE COMMUNITIES THAT ARE NOT IDENTIFIABLE IN DATASETS AT THIS POINT AND DO NEED MORE SPECIFICITY ACROSS DATASETS AND CODES. THAT'S JUST A QUESTION. YOU'RE GOING TO HAVE SUCH RICH LEARNING THAT COULD MOVE THE NEEDLE FOR COMMUNITIES IN WAYS BEYOND WHAT THIS PROJECT IS INTENDED TO DO. >> YEAH, AND I THINK THAT, YOU KNOW, THE WAY TO APPROACH THAT AS A FUNDAMENTAL, YOU KNOW, ISSUE OR PROBLEM SET THAT YOU NEED TO ADDRESS BEFORE YOU CAN GO FORWARD, I MEAN, THIS IS EXACTLY WHAT THE ReCOVer EVERYDAY WITH LONG COVID DID BECAUSE WE DIDN'T HAVE AN ICD-10 CODE FOR LONG COVID UNTIL SOMETHING LIKE OCTOBER OR NOVEMBER OF LAST YEAR. SO THERE'S ACTUALLY A LOT MORE PEOPLE IN THE DATABASE WHO WE NOW KNOW FROM THE ALGORITHM THAT THEY HAVE DEVELOPED WHO HAVE LONG COVID, BUT NEVER HAVE GOTTEN THAT -- NEVER NECESSARILY HAVE GOTTEN THAT DIAGNOSTIC CODE. SO I THINK THAT SORT OF METHODOLOGY, THOSE APPROACHES ON HOW YOU GO ABOUT DOING THAT IS SOMETHING THAT I THINK IS ANOTHER OUTCOME OF N3C INDEPENDENT OF COVID PER SE THAT I THINK WILL REALLY BENEFIT AS YOU MENTIONED IN RARE DISEASE COMMUNITY IF YOU DON'T HAVE AN ICD-10 REALLY TRYING TO DEVELOP THAT VERY VALIDATED RELIABLE CLINICAL PHENOTYPE -- THAT SHOULD NOT ONLY ALLOW YOU FIND THE INDIVIDUALS WHO ARE OUT THERE BUT MAY PROBABLY ALSO LEAD TO NOVEL WAYS OF DIAGNOSING NEW CASES THAT APPEAR BEFORE EVERYONE JUST STARTS, YOU KNOW, AND I THINK I HAD A CONVERSATION ONE TIME WITH PATTI BRENNAN AND SAID ONE OF THE INTERESTING THINGS ABOUT RARE DISEASES IS RATHER THAN LOOKING AT THE LABORATORY RESULTS, IT MAY JUST BE INFORMATIVE TO LOOK AT WHAT LABORATORY TESTS GET ORDERED, REGARDLESS OF WHAT THE LABORATORY TEST RESULT SHOWS. THAT MIGHT BE ACTUALLY SEMI DIAGNOSTIC OF WHAT RARE DISEASE THE INDIVIDUAL HAS. THAT'S THE APPROACH WITH AN N3C-TYPE DATABASE WITH EHR RECORDS YOU CAN BEGIN TO REALLY ASK AND GET AT AND I THINK, YOU KNOW, THE EXPERIENCE THAT'S BEEN GAINED BY THE N3C COMMUNITY WILL JUST -- IS GOING TO PAY OFF SO WELL IN A LOT OF OTHER DISEASE SITUATIONS. >> AND I'LL JUST ADD TO THAT TOO, YOU KNOW, I THINK THE ISSUE ABOUT THE ICD-10 CODES BEING A DEARTH OF THEM FOR RARE DISEASES, WE'VE BEEN TRYING TO THINK ABOUT THIS AS WELL, IT'S FOLLOWING ON SORT OF THE STUDY WE DID THROUGH THE IDeAs PROGRAM, LOOKING AT 14 RARE DISEASES TO UNDERSTAND FROM OUR PERSPECTIVE FROM THE ELECTRONIC HEALTH RECORD PERSPECTIVE THE BURDEN AND COST OF RARE DISEASES. AND FROM THAT WE WERE ABLE TO EXTRAPOLATE FROM 14 DISEASES TO 7,000, BUT VERY ROUGH ESTIMATE. THE GREAT THING, IT MIRRORED OTHER GREAT WORK AMY HAD DONE THROUGH THE LEVIN GROUP AND SO WE DO THINK WE'RE PRETTY CLOSE ON UNDERSTANDING THE COST BURDEN FOR DIRECT MEDICAL CARE COSTS FOR RARE DISEASES BUT IT'S AN ESTIMATE STILL. WE REALLY DON'T KNOW. SO FOR THESE ICD-10 CODES, MIKE IS RIGHT, IT'S GOING TO TAKE MORE CREATIVITY THAN PERHAPS GOING DOWN ICD-10 ROUTE. THERE ARE REASONS FOR CODES, THEY ARE NEEDED, FOR PURPOSES, BUT THEY ARE NOT NECESSARILY SUFFICIENT FOR RESEARCH PURPOSES AND I THINK RESEARCH CAN START TO LEAD THE WAY. AND THERE ARE PEOPLE, THERE IS A RARE DISEASE GROUP WHERE THOSE ARE THE CLINICAL GROUPS WITHIN N3C THAT ARE COALESCING AND I THINK THERE'S -- YOU KNOW, A REAL INTEREST IN LOOKING AT HOW WE CAN START TO THINK ABOUT DIFFERENT RARE DISEASES. WITH THE DATASET FROM COVID IT'S GOING TO BE DIFFICULT BUT WILL GIVE A GOOD START. WITH THAT, THEN BACK TO YOUR QUESTION, ANNIE, THE IDEA IS DEFINITELY TO START ENGAGING MORE OF THE COMMUNITY TO UNDERSTAND HOW WE CAN GET THAT BACK INTO, YOU KNOW, LEVERAGING THIS MORE ACROSS THE ECOSYSTEM. WE HAVE A WAYS TO GO TO REALLY LEARNING ABOUT THE VALIDITY OF THE APPROACHES WE CAN UNDERTAKE, AND BUT I THINK ONCE WE GET THERE THEN WE'LL HAVE A PLAN IN PLACE TO BE ABLE TO WORK WITH THE REST OF THE ECOSYSTEM TO GET THEM MORE INGRAINED INTO THE CLINICAL USAGE OF THESE SORTS OF CODING WAYS. >> AMEN TO JONI FOR CODES NOT BEING EFFICIENT. THEY ARE USED DIFFERENTLY ACROSS HOSPITALS, BETTER RESOURCES HAVE RESOURCES TO MAJOR PATIENTS LOOK SICKER, SAFETY NET HOSPITALS HAVE SICKERS PATIENTS SO ICD-10 CODES ARE NOT RELIABLE, THINGS HAVE HAPPENED WITH ADMINISTRATIVE DATA, BECAUSE IT'S EASY TO GET TO AND YOU CAN USE IT AND I DON'T KNOW HOW CLEAN IT IS, PROBABLY NOT SO CLEAN. THAT'S CORRECT. WE NEED TO USE DATA WHERE DEFINITIONS ARE THE SAME AND THEY ARE USED CONSISTENTLY AND NOT ACROSS DIFFERENT PLACES. AS A CLINICIAN WHO USES ELECTRONIC HEALTH RECORDS YOU'RE FORCED TO PUT IN CODES WITH 'EMIC AND EHRS TO GET YOUR WORK DONE. IF THE CODE ISN'T CORRECT YOU CAN'T REMOVE IT BECAUSE THAT'S THE REASON THEY CAME TO SEE YOU IN THE FIRST PLACE. MY TRUST OF ICD-10 CODES, VERY LOW. >> YEAH. HEARD, PAULA. IT'S A CONCERN. MARSHALL MENTIONED THE HPO, HUMAN PHENOTYPING ONTOLOGY. THERE'S SNOMED TERMS, MEANT TO GET MORE CLINICAL TERMS THAT ARE USED IN ELECTRONIC HEALTH RECORD AS OPPOSED TO BEING RELATED TO A DISEASE DIAGNOSIS, AND THEN AGAIN THERE'S STILL THIS LINE THAT WE NEED TO DRAW BETWEEN DIAGNOSTIC THAT IS RECOGNIZED FOR PURPOSES OF REIMBURSEMENT. AND THEN OF COURSE THE RESEARCH. AND SO IT'S -- THERE'S STILL AN IMPORTANT THREAD WE NEED TO PULL. BUT I THINK THIS IDEA OF SPEAKING ABOUT HOW TO USE CLINICAL TERMS MORE SPECIFICALLY FOR RESEARCH PURPOSES TO GET US TO THE STAGE WHERE WE CAN GET AT DIAGNOSTICS FASTER, THAT'S THE IDEA WE'RE THINKING ABOUT. AND ICD-10, 9, 10, 11, NOT QUITE IT YET. >> WE NEED AN ELECTRONIC CLINICAL PHENOTYPE IS WHAT YOU'RE GETTING AT. >> YEAH. >> EXACTLY. EXACTLY. >> GOING INTO ANY EHR WILL THAT PICK OUT THE PATIENTS, RELIABILITY OF WHAT WE THOUGHT ICD-10 CODES WERE SUPPOSED TO DO BUT DON'T. >> AND HAVING NOW A LOT OF EHR LINKED TO GENETIC INFORMATION FROM AT LEAST SEGMENT OF SUBPOPULATION, THROUGH THAT ANCHOR POINT, PULL IN AN ELECTRONIC FINGERPRINT, AND THAT'S AN EFFORTS YOU'RE BEAUTIFULLY SET UP TO LINK TO GENETIC INFORMATION AVAILABLE, FEDERATED DATABASES, A WAY TO DO THAT UTILIZING THE PLATFORM, SO THOSE ARE STARTING POINTS AND PETER ROBINSON IS A BEAUTIFUL PERSON WITH THIS APPROACH TO ALLOW BOTTOM-UP TO DO REVERSE ENGINEERING AND THAT MIGHT CREATE SO THAT YOU ALLUDED TO WHICH TESTS ARE ORDERED. THESE TYPE OF FINGERPRINTS YOU CAN PULL IN WITH THE ENTIRE DATASET. YOU NEED TO HAVE CRITICAL MASS. I THINK YOU HAVE THAT ALREADY IF YOU CONNECT THE DOTS. CTSAs ARE ABLE TO DO THAT IF THEY CONTINUE WITH THE SENSE OF URGERY FROM THE COVID PANDEMIC. >> A QUICK EXAMPLE, ONE THING WE'VE DONE WITH N3C THIS WAS SOMETHING THAT NIAID APPROACHED ME ABOUT, IT'S IN PLACE NOW. AND THAT IS COULD WE CONNECT VIRAL VARIANT SEQUENCE DATA WITH THE INDIVIDUAL PATIENT'S EHR RECORD AND WE CAN NOW DO THAT. AND THAT IS VIRAL DNA DATABASE THAT CERTAIN INSTITUTIONS DOING SEQUENCING, THEY MAINTAIN, THEY KNOW THE PATIENT IT'S LINKED TO, WE CAN TOKENNIZE DATABASE AND LINK TO REGARDS TO LOOK AT GENETIC SEQUENCE OF INDIVIDUAL VIRUSES AND CONNECT THAT UP WITH THEIR CLINICAL COURSE. AND SO I THINK, YOU KNOW, IT'S JUST ANOTHER STEP IF YOU'RE TALKING ABOUT THE PATIENT'S DNA WHICH WILL BE STORED IN THIS EPPIC DATABASE, PROBABLY NOT IN THE CHART FOR A LONG TIME. >> THERE'S CMS DATA NOW. WE GOT THAT -- >> THAT'S VERY RECENT. >> THAT WAS - THAT TOOK A WHILE BUT IT'S IN THERE NOW. THAT'S GOING TO ADD HUGE VALUE TO UNDERSTAND THE INTERACTIONS WITH THE HEALTH CARE SYSTEM AS WELL. AND THEN MORTALITY DATA IS WOEFULLY INADEQUATE IN ELECTRONIC HEALTH RECORDS, BRINGING THOSE DATA IN AS WELL SO LINKAGES ARE CRITICALLY IMPORTANT AND THEN PAULA MENTIONED IT BEFORE, BUT THE SOCIAL DETERMINANTS OF HEALTH KINDS OF PUBLIC DATABASES REALLY ADD VALUE TOO. THERE'S A VARIETY OF ASPECTS THAT ARE CRITICAL FOR THIS. AND, YOU KNOW, IN TERMS OF THOSE DATA LINKAGES, I WANT TO GIVE A SHOUT OUT TO KEN AND SAM WHO MADE THIS WORK HAPPEN. AND THEY ARE WORKING ACROSS NOT JUST THE RESEARCH ENTERPRISE BUT ALSO MAKING SURE THAT ALL OF THE MAPPINGS ARE GOING TO BE AVAILABLE FOR THE FDA WORK, REGULATORY PURPOSES, MAPPING TO THE COMMON DATA MODEL IS A CRITICAL ASPECT THAT NEEDED TO BE BUILT IN FROM THE BEGINNING AND THEY HAVE DONE THAT SO I THINK THAT IT IS A VERY WELL-ROUNDED WAY OF LOOKING AT THIS, GENERATING PHENOTYPES FOR RARE DISEASE PHENOTYPES CRITICAL AS WELL TOO. >> THIS IS SOMETHING WE'RE SPENDING A LOT OF TIME ON IN THE FIELD. ONE THING TO WHAT JONI SAID REAL QUICK ABOUT CDISC AND EVERYTHING, WE WORKED WITH FDA TO MAKE SURE AS MUCH MAPS AS POSSIBLE, THAT'S A SEPARATE THING. WE DID AN INTERESTING THING. WE TOOK THE ORPHAN RARE DISEASE ICD-10 CODES, FOR 11 THEY ARE ONLY GOING TO ADD 5,000 MORE CODES AND STOP DOING RARE DISEASE SO THAT'S NOT GOING TO GET BETTER, IT'S GOING TO STAY THE SAME. WE MAPPED AGAINST ALL THE PATIENTS IN OUR DIVISION AND HOW MANY TIMES THEY WERE SEEN, AND WE ACTUALLY GOT MAPPING ACROSS ABOUT THREE-QUARTERS OF THE PATIENTS HAD AN ICD-10 THAT MAPPED UP WITH WHY THEY WERE BEING SEEN AND TOOK 1.5 MILLION VISITS AT CHILDREN'S NATIONAL MAPPED THEM AGAIN THE ORPHANETTE DISEASE LIST, WE SHARED THAT WITH YOU, JONI, AT SOME POINT IN TIME. IF YOU WANT A FRESH COPY WE CAN. WE WENT THROUGH, ANNOTATED ACROSS DISEASE CATEGORY. YOU COME TO A CHILDREN'S HOSPITAL ONE TIME, YOU HAVE 12% CHANCE OF RARE DISEASE CODE, MORE THAN ONE 32% OF HAVING AN ICD-10 RARE DISEASE CODE. IF YOU GET ADMITTED, IT'S 20%. BUT WE'RE ALSO ABLE TO GO BACK AND PULL THE CHARGES, MEDICAL CHARGES NET COST AND EVERYTHING FOR THOSE PATIENTS. I HAVE ALL THAT DATA, JONI, OVER -- SINCE ROLLOUT OF ICD-10 AND SO WE KNOW THE PHYSICIAN COST, NOT THAT MUCH, FACILITY CHARGES FOR THESE PATIENTS ARE ENORMOUS. >> YEAH. >> IF YOU WANT TO, WE'VE GOT IT MAPPED OUT. >> YEAH, WE SHOULD TAKE A LOOK AT THAT. THAT'S GREAT, MARSHALL. >> YOU CAN TELL ME WHERE TO PUBLISH IT. I HAVEN'T FIGURED OUT WHERE YET. I NEED SUGGESTIONS. >> YEAH, SURE. WE CAN DEFINITELY DO THAT. AND THE OTHER THING YOU MENTIONED, SEQUENCE DATA, BACK TO MATHIAS' COMMENT, IS THAT GOING TO HELP, PROBABLY NOT BECAUSE THEY ARE NEWER DISEASES. >> CORRECT. I MAPPED THAT OUT, THERE'S 6.4 NEW DISEASES DESCRIBED PER WEEK. >> WOW! >> THERE'S CURRENTLY 7,253. I DID THIS TALK THE OTHER DAY AND HAVE THE NUMBER LISTED. SINCE 2000, WHEN WE FINISHED THE DRAFT, WHICH IS WHEN MOST HAVE BEEN DESCRIBED, YOU'RE ADDING AT RATE OF 6.4 PER WEEK. WE TALKED CERNER INTO BUILDING A VARIANT CAPTURE INTO EMR, MOST GENETIC TEST RECORDS ARE LOST IN A PDF. WE'VE GOT WORK ON PARSING TO EXTRACT DATA BUT MOVING FORWARD WE TALKED MAJOR SEQUENCING COMPANIES DO DIRECT DUMPS INTO EMR SO VARIANTS ARE CAPTURED AND WEB LINKED BACK TO THE DIFFERENT DATABASES THAT CAPTURE VARIANTS AND UPDATE WHEN VARIANTS ARE DETERMINED PATHOLOGIC OR NOT. WE'VE BEEN WORKING OUT COOL WAYS TO CAPTURE THOSE THINGS GOING FORWARD BUT I THINK IF WE DON'T DO THIS WELL, IT'S REALLY HARD TO DO THE WORK. >> THAT'S GREAT TO HERE. I'M GLAD THAT THE SEQUENCE, AT LEAST THE VARIANT FILES ARE GETTING CAPTURED NOW. >> IT'S VARIANT FILES. YEAH, THEY BALKED DURING THE WHOLE SEQUENCE BUT WE WANTED TO CAPTURE MICROARRAY DATA, PANEL DATA, BECAUSE THE MAJORITY OF THE DATA IS NOT WHOLE EXOME OR GENOME. WE HAD TO GET IT INTO THE RIGHT NOMENCLATURE. IT'S A COOL THING. SETH BERGER LED THAT PROGRAM BUT THEY ARE ROLLING OUT ACROSS CERNER. >> THAT'S GREAT TO HEAR. SO ONE INTERESTING CAVEAT, AND I DON'T KNOW IF PENNY IS ON, SHE MIGHT BE, PENNY AND MEREDITH ON OUR TEAM HAVE REALLY BEEN LEADING THE POLICY ASPECTS OF N3C AND THEY ARE NOT SMALL. BUT WE'RE TALKING ABOUT ADDING GENOMIC DATA INTO ELECTRONIC HEALTH RECORDS, THERE'S SOME GROUPS DOING THIS, GEISINGER STARTED THIS, AND THEN MARSHALL IS TALKING ABOUT THIS APPROACH WITH THE VARIANT FILES. THERE ARE POLICY CONSIDERATIONS HERE AS WELL BECAUSE OF THE POTENTIAL IDENTIFIABILITY WITH SEQUENCE DATA, I THINK IT REMAINS TO BE SEEN IF YOU CAN MASK OR DO SOME PRIVACY KINDS OF MANIPULATIONS TO THE VARIANT FILES BUT THIS IS SOMETHING I THINK THAT ALSO N3C FROM THE POLICY PERSPECTIVE CAN START TO LEAD FOR THE COMMUNITY. RIGHT NOW, BECAUSE OF POLICY CONCERNS, WE DON'T HAVE GENOMIC DATA WITHIN -- HUMAN GENOMIC DATA. WE DO HAVE VIRAL VARIANT SEQUENCE DATA. BUT NOT HUMAN GENOMIC SEQUENCE DATA FOR A VARIETY OF REASONS IN THAT REGARD BUT I THINK THAT THESE ARE ISSUES THAT WE NEED TO START UNDERSTANDING MORE ABOUT TO SEE IF THERE ARE WAYS WHICH WE CAN MOVE FORWARD WITH THAT THOSE IMPORTANT PIECES OF INFORMATION. PENNY, DO YOU WANT TO ADD ANYTHING? >> SURE. THANKS, JONI. YOU KNOW, WE HAVE BEEN IN DISCUSSIONS WITH THE NIH OFFICE OF SCIENCE POLICY. I THINK THEY THEMSELVES RECOGNIZE THE VALUE AND REALLY THE PACE OF RESEARCH DISCOVERY USING GENOMIC DATA. AND SO THEY RECENTLY PUT OUT A REQUEST FOR COMMENT ON THE POTENTIAL INCLUSION OF GENOMIC DATA IN THIS KIND OF WAY. SO THEY ARE NOT STAYING SILENT AND NOT TRYING TO HOLD FAST TO THE EXISTING POLICY. POLICY TAKES TIME TO CHANGE BUT I DO THINK THAT THIS IS SOMETHING THEY ARE TAKING VERY SERIOUSLY. THEY ALSO HAVE BEEN WORKING CAREFULLY WITH US AS WE STOOD UP THE N3C. AND THEY KNOW THAT WE HAVE TAKEN I THINK A VERY COMPREHENSIVE APPROACH IN THE POLICY ARENA FOR HOW THE N3C CAN BE USED WHERE WE LOOK AT NOT ONLY THE REGULATIONS, NIH POLICIES, THE SECURED PRACTICES WE PUT ON THE N3C PLATFORM, BUT ALSO KIND OF AS A LAST-MILE EFFORT TO REALLY ADDRESS ISSUES OF PRIVACY, WE ALSO PUT QUITE A BIT OF RESPONSIBILITY ON THE USERS THEMSELVES. SO THAT IT BECOMES A VERY COMPREHENSIVE EFFORT TO TRY AND PROTECT THE PRIVACY OF THE DATA, YET ALSO MAKE THIS DATA AS WIDELY AND BROADLY AS ACCESSIBLE AS WE CAN. >> PENNY HIT THE NAIL ON THE HEAD. THIS IDEA OF NOT JUST RELYING ON, FOR EXAMPLE, HIPAA POLICIES TO PROTECT PATIENT PRIVACY, THIS KIND OF APPROACH REQUIRES US TO COME AT IT FROM MULTIPLE ANGLES TO WORK ON THAT PRIVACY PROTECTION AND THAT COMES FROM THE USER PERSPECTIVE, DATA CONTRIBUTED PERSPECTIVE, STEWARDSHIP OF THE DATABASE ITSELF, ALL OF THESE ASPECTS NEED TO COME TO PLAY, TO HAVE THAT PRIVACY PROTECTION INCLUDED. MATTIAS. >> WITH U.K. BIOBANK, HEALTHCARE SPECIFIC GENOMIC DATABASES, HOW THEY HAVE BEEN REGULARLY TESTED TO BE LINKED WITH EHR SYSTEMS, PROTECTING PATIENT INTERESTS, AS WAS MENTIONED FEDERATED IS A GOOD ONE TO START. EACH OF THE INDIVIDUAL FEDERATED KNOW SAMPLE SIZE CAN BE INDIVIDUALLY INFORMATIVE. AND THEN YOU CAN START TO USE AGGREGATED DATA TO BRING THAT TOGETHER, BEAUTIFUL ACTIVITIES WHERE YOU CAN USE ALGORITHMS AND YOU CAN HOOK THEM ON YOUR FEDERATED DATA FRAMEWORK AND HAVE MEASURES TO BRING THEM BACK. WITH N3C YOU HAVE ESTABLISHED THIS IS A WAY THE SYSTEMS ARE ABLE TO WORK BECAUSE BEFORE THAT BUSINESS PEOPLE AT HEALTH CARE CENTERS SAY THIS IS NOT PERMISSIBLE AND NOT POSSIBLE, THAT BARRIER IS GONE. MAKING SURE YOU PERPETUATE THAT ACCESS AND THAT STRATEGY IS A CRITICAL FEATURE FOR THE NEXT 6 TO 12 MONTHS. >> SO TRUE. I COULDN'T AGREE MORE. WE HAVE MORE CRITICAL MASS OF DATA WITHIN INDIVIDUAL PLACES NOW SO THAT FEDERATED MODEL COULD GET MORE POWERFUL. AND I THINK THAT'S IMPORTANT. THE OTHER ASPECT IS THAT STILL RUN RISK OF INCLUDING BIAS INTO THOSE SYSTEMS AND SO THAT'S SOMETHING I THINK WE ALL HAVE TO WATCH OUT FOR, BUT AT THE SAME TIME, YOU KNOW, WE CAN AS MIKE LIKES TO SAY, IT'S NOT FEDERATED VERSUS CENTRALIZED, IT'S A COMMA AND, LOOKING AT USEFULNESS OF PROS AND CONS OF BOTH APPROACHES TO MAXIMIZE WHAT WE NEED TO DO FOR A GIVEN QUESTION AND I THINK THAT THE OTHER IDEAS HERE IS AS WE BUILD OUT HIGH PERFORMANCE COMPUTING MODELS TO BRING DATA TOGETHER FROM EPHEMERAL WAY, CENTRALIZED MANNER, IT COMES AND GOES SO IT'S NOT PERSISTENT AND I THINK THOSE KINDS OF APPROACHES ARE THINGS WE'D LIKE TO PURSUE AS WELL TO AGAIN ADDRESS PRIVACY CONCERNS. WE WANT TO KICK THE TIRES TO SEE WHAT'S WORKABLE. >> PENNY? >> I WAS GOING TO SAY NOT ALL OF THESE ISSUES ARE APPLICABLE TO GARD BUT THERE ARE MANY EFFORTS THAT ARE BEING MADE TO MODERNIZE GARD AND SOME OF THESE ARE TYING INTO THESE SAME TOPICS THAT WE'RE DISCUSSING. BUT THE MODERNIZATION OF GARD IS REALLY TO, LIKE N3C, TO BRING MORE INFORMATION AND MORE DATA TO MAKE IT ACCESSIBLE AND USABLE FOR THE PEOPLE THAT NEED ACCESS TO IT. MY UNDERSTANDING IS THAT THE GARD AS IT HAS EXISTED HAS BEEN VERY CUSTOMIZED TO WHAT PEOPLE WERE LOOKING FOR BUT NOW WE'RE TRYING TO TAKE A BROADER SWEEP. LIKE WE HAVE WITH THE N3C TO MAKE A WEALTH OF INFORMATION THAT IS AVAILABLE ACCESSIBLE TO THE PUBLIC AND TO THE HEALTHCARE WORKERS TRYING TO DO RESEARCH ON IT. >> GREAT. THANK YOU. ALL RIGHT. ANY OTHER -- GREAT DISCUSSION. REALLY APPRECIATE IT. ANY OTHER QUESTIONS OR COMMENTS? FOR MIKE OR ME? OR PENNY? >> JUST TO REITERATE AND WE DIDN'T GET TO THE DISCUSSION OF THAT BUT THE T4 RESEARCH REALLY COUNTER ACTING MISINFORMATION IN THE WAY WE BRING INFORMATION BACK TO COMMUNITY IS CRITICAL. AND SEPARATE DISCUSSION BUT CERTAINLY AN AREA WE FALL SHORT ON SO MANY LEVELS, IT'S NOT AN AREA WHERE I CAN SPEAK OUT OF MY OWN RESEARCH EXPERIENCE EXCEPT THAT, YOU KNOW, WITNESSING HOW DIFFERENCE SOCIETIES ARE CLEARLY UNDERPERFORMING COMPARED TO PROGRESS IN OTHER AREAS AND IT'S GREAT TO SEE MIKE, THE NEXT CHAPTER IN THE T4D SPACE, WHERE THEY ARE COMING FROM A LOT BETTER EQUIPPED THAN WE WERE. >> YEAH, NO, I FULLY AGREE. ONE OF THE THINGS THAT IS -- IT WAS DISAPPOINTING TO HEAR BUT OUT OF THAT REAL WORLD EVIDENCE FOR MONOCLONALS THEY DID AS PART OF THAT PROJECT COMMUNITY OUTREACH TO MAKE THEM AWARE MONOCLONALS WERE AVAILABLE AND TOBACCO -- AND TO MAKE HEALTH CARE WORKERS KNOW THEY WERE AVAILABLE. THE AVERAGE PERSON ON THE STREET DOESN'T KNOW, THE AVERAGE HEALTH CARE PROVIDER DIDN'T KNOW A LOT MORE, DIDN'T KNOW PERFORMANCE CHARACTERISTICS, DIDN'T KNOW WHO THEY WERE INDICATED FOR, WHERE TO GO TO GET THEM. THEY DIDN'T -- THERE WAS AN EDUCATIONAL COMPONENT TO MAKE THE HEALTH CARE COMMUNITY, THE PROVIDERS WHEN I WAS IN MEDICAL SCHOOL, THE DEAN USED TO SAY, THE SEA LEVEL PRACTICING PHYSICIANS MAKE THEM AWARE OF WHAT WAS AVAILABLE. AND WE HAVE THIS SORT OF -- I THINK THE ACADEMIC COMMUNITY KIND OF HAS A LITTLE BIT OF A NAIVE ASSUMPTION THAT, OH, I PUBLISHED A PAPER IN THE NEW ENGLAND JOURNAL, EVERYBODY READ THAT, THE NEXT DAY THEY CHANGE THE WAY THEY PRACTICE MEDICINE, THAT'S NOT HOW IT WORKS. PART OF THE RT4 IS NOT JUST GETTING THOSE INTERVENTIONS OUT INTO THE COMMUNITY BUT ACTUALLY DISSEMINATING THAT INFORMATION TO THE HEALTH CARE COMMUNITY BECAUSE, YOU KNOW, WE LAMENT THAT IT TAKES 15 YEARS TO BRING A DRUG TO MARKET BUT THE STUDIES SUGGEST IT TAKES 17 YEARS TO GET CLINICIANS TO USE THE DRUG AFTER IT'S ON THE MARKET. AND THAT'S JUST WAY TOO LONG. WE'VE GOT TO DO BETTER. WE HAVE TO TREAT DISSEMINATION OF OUR RESEARCH RESULTS AS IMPORTANTLY AS WE TREAT THE PUBLICATION OF THOSE RESULTS. >> YEAH. AND ALSO TOO, MATTIAS, WE FAILED, COMMUNICATION OF SCIENCE AREA, I THINK IT WAS ALSO CAUGHT OFF GUARD REALLY AT HOW PERVASIVE THAT WAS. WE HAVE AN OPPORTUNITY I THINK NOW THAT WE'RE, YOU KNOW, IT'S -- I DON'T LIKE TO SAY THAT COVID IS IN OUR REAR-VIEW MIRROR, WE STILL HAVE MANY DEATHS PER DAY AND NEED TO BE VIGILANT ABOUT IT. BUT WE ALSO HAVE AN OPPORTUNITY HERE TO UNDERSTAND WHAT WE HAVE -- WHERE WE DID GO WRONG AND DO SORT OF AN ANALYSIS, AS A SCIENTIFIC COMMUNITY NEED TO THINK ABOUT THIS EVEN MORE. THE AWARDS THAT MIKE MENTIONED, SERGIO HAD ONE ON OUTREACH TO THE COMMUNITY ON MISINFORMATION AND TRUST IN SCIENCE, AND I THINK THERE ARE FOLKS WHO ARE REALLY THINKING ABOUT THIS DEEPLY AND I HOPE THAT WE CAN LEARN FROM THAT AS AN OPPORTUNITY NOW IN THIS TIME OF TRANSITIONING PERHAPS FROM LONG COVID TO ACUTE COVID MORE TO LONG COVID AND START TO WRITE SOME OF THOSE AREAS THAT WE NEED TO WRITE. AND I DON'T KNOW THE ANSWERS BUT I'D LOVE TO HEAR YOUR THOUGHTS ON THIS PARTICULAR ISSUE IF YOU HAVE THEM. AND WE'LL KEEP OF COURSE TALKING ABOUT THIS MORE. MISINFORMATION OF SCIENCE IS SOMETHING WE THINK ABOUT MORE BROADLY AT NIH TOO IN TERMS OF HOW WE COMMUNICATE. OKAY. ANYTHING ELSE? WE MADE UP FOR TIME. >> I APOLOGIZE FOR GETTING US BACK ON TRACK. >> FANTASTIC DISCUSSION. REALLY APPRECIATE IT. I'LL TURN IT BACK TO YOU, ANNA. AND WE HAVE A SCHEDULED BREAK IF I RECALL. >> WE DO NOW THAT WE'RE BACK ON TRACK, WE CAN GO WITH OUR BREAK 3:30 TO 3:40 AS PLANNED. WE WILL GET STARTED ON THE CONCEPT CLEARANCE SECTION OF OUR OPEN COUNCIL. WE HAVE THREE CONCEPTS THAT WILL BE PRESENTED. ONE FROM CHRISTINE COLVIS' SHOP ON OFFICE OF DRUG DEVELOPMENT PARTNERSHIP PROGRAM, AND THEN TWO FROM OFFICE OF SPECIAL INITIATIVES AND STRATEGIC ALLIANCE FOR THE SBIR COMPONENT AS WELL. AND SO FOR THESE THEY WILL GIVE A BRIEF OVERVIEW DELIVERED BY -- GENERALLY BY THE DIRECTOR WHO WILL INTRODUCE THE PROGRAM PERSON PROVIDING THE DETAILS OF THE CONCEPT AND WE'LL HAVE DISCUSSANTS AVAILABLE AND ALLOW MEMBERS TO COMMENT FROM COUNCIL. AND WE'LL OPEN THE FLOOR FOR ADDITIONAL DISCUSSION BEFORE WE VOTE. I NEED TO REMEMBER THE FACT THAT WE DO VOTE AND MAKE SURE WE SAVE TIME FOR THAT. WITH THAT, I WOULD LIKE TO INTRODUCE DR. CHRISTINE COLVIS PRESENTING THE OVERVIEW AND CONCEPT PRESENTER FOR THE INITIATIVE. TAKE IT AWAY. >> IN EFFORT TO MAKE IT EASY EASIER, I ANIMATED THE SLIDES BUT ZOOM MESSES WITH THE TIMING, SO WE'LL SEAL WHAT HAPPENS, AN ADVENTURE. IT'S A PLEASURE TODAY TO BE SETTING UP FOR TYLER BECK TO TELL YOU ABOUT THE NEW CONCEPT WE HAVE. SO, THE FIRST SLIDE PLEASE. SO, THIS IS LAST SEPTEMBER, OVERVIEW OF THE OFFICE, SHOWING VARIOUS PROGRAMS, TWO IN GRAY, PROGRAMS ARE NIH-WIDE PROGRAMS THAT WE MANAGE ON BEHALF OF THE NIH AND THE PURPLE ONES ARE THE ONES THAT ARE NCATS INITIATED THINGS. AND ASSETS FLEW IN THERE WHILE I WAS GIVING MY INTRO, AND THAT IS THE NEW ONE WE'RE GOING TO TELL BUT TODAY. NEXT SLIDE ASCETTS IMPROVE EFFICIENCY OF DRUG DEVELOPMENT OR TECHNOLOGIES THAT CAUSE US TO RETHINK THERAPEUTIC STRATEGIES. THEY COULD BE TECHNOLOGIES THAT IMPROVE DRUG TARGETING OR DRUG DELIVERY. THE IDEA ON THE NEXT SLIDE IS THAT WE WANT TO PROVIDE SEED FUNDING FOR INVESTIGATOR INITIATED DEVELOPMENT OF TECHNOLOGIES FOR TRANSLATIONAL SCIENCES, THIS IS SOMETHING WE CONSIDER HIGH-RISK, HIGH-REWARD PROGRAM, MITIGATE RISK BY OFFERING MODEST BUDGET, JUST SEED FUNDING, USING A NON-RENEWABLE SHORT PERIOD OF SUPPORT. REALLY SOMETHING THAT WILL HELP PEOPLE TEST THE WATERS, SEE WHETHER IT LOOKS LIKE THE TECHNOLOGY IS GOING TO WORK, AND THEY WOULD BE ABLE TO GO ON WITH DEVELOPMENT FROM THERE. WITH THAT I'M GOING TO STAND IT OVER TO DR. BECK WHO YOU'VE HEARD FROM BEFORE. HE HAS IN THE PAST GIVEN PRESENTATIONS ON LITCOIN TO THOSE ON COUNCIL AT THAT TIME. >> THANK YOU FOR THE OPPORTUNITY TO PRESENT THIS CONCEPT, AS CHRISTINE AND I FEEL THAT IT FILLS A GAP IN RESEARCH FUNDING OPPORTUNITIES FOR TRANSLATIONAL RESEARCHERS. OFFERING SEED FUNDING FROM HYPOTHESES TO FLESHED OUT PROTOTYPE TECHNOLOGIES BEFORE ENGAGING STAKEHOLDERS FOR LATER PROJECT DEVELOPMENT. WE CALL THIS THE AWARDS SUPPORTING CUTTING EDGE TECHNOLOGIES FOR TRANSLATIONAL SKY ENSURE, ASCETTS, PROPOSING A FUNDING METHOD TO ALLOW EARLY STAGE DEVELOPMENT OF BIOMEDICAL TECHNOLOGIES WHICH CAN BE DIFFICULT TO SECURE FUNDING FOR BECAUSE THERE'S LACK OF FUNDING FOR INVESTIGATOR INITIATED INNOVATION IN OUR FIELD. AND THIS CONCEPT IS BASED ON SUCCESSFUL PROJECT THAT NIDA HAS BEEN RUNNING FOR SEVERAL YEARS CALLED CUTTING EDGE BASIC RESEARCH AWARDS WHICH HAS RESULTED IN SEVERAL EXCITING PROJECTS BEING FUNDED, BUT AS YOU CAN TELL FROM THE NAME THAT PROGRAM FOCUSING STRONGLY ON BASIC SCIENCE AWARDS AND WE BELIEVE TRANSLATIONAL RESEARCH COULD MAKE GOOD USE OF A SIMILAR FUNDING PROGRAM BUT FOCUSED MORE TIGHTLY ON TECHNOLOGY DEVELOPMENT. WE EXPECT TO FUND EXCITING EARLY STAGE INNOVATIVE TECHNOLOGY DEVELOPMENT PROJECTS WITH SEED FUNDS THROUGH THIS PROGRAM. AS I WAS PREPARING FOR THIS MEETING I CAME ACROSS EVIDENCE WE'RE NOT THE ONLY RUNS WHO RECOGNIZED THIS GAP IN FUNDING IN TRANSLATIONAL RESEARCH. AS SHOWN FROM UNC'S CHAPEL HILL WEBSITE WHICH SHOWS SOURCES OF FUNDING FOR DIFFERENT STAGES OF TRANSLATIONAL RESEARCH FUNDING. UNC HAS RECOGNIZED LACK OF FUNDING OPPORTUNITIES FROM NIH AND NSF FOR TECHNOLOGY DEVELOPMENT. SO THE GOALS OF THE PROJECT ARE FOCUSED ON CREATING FUNDING OPPORTUNITY TO ALLOW FOR INNOVATIVE TECHNOLOGY DEVELOPMENT IN THE TRANSLATIONAL SCIENCE SPACE AND TO STIMULATE DEVELOPMENT OF TECHNOLOGIES THAT COULD BE FURTHER DEVELOPED UNDER SMALL BUSINESS SUPPORT PROGRAMS LIKE STTR AND SBIR OR PICKED UP BY OTHER INVESTORS. WE ENVISION THESE AS SHORT AWARDS ALONG SIMILAR SIGNS AS NIDA'S R21 GRANTS, MAXIMUM TWO YEARS, FITTING IN NCATS MISSION AS THEY WILL SUPPORT DEVELOPMENT OF NEW TECHNOLOGIES AND LEAD TO ADVANCEMENTS THAT BRING MORE TREATMENTS TO MORE PEOPLE MORE QUICKLY. WE HOPE THEY WILL LEAD TO STTR OR DIRECT ENGAGEMENT WITH TECH OR PHARMA LEADERS. AND WE HOPE TO SEE UPTAKE OF THIEVES NEW TECHNOLOGIES BY OTHER TRANSLATIONAL RESEARCHERS. NEXT SLIDE PLEASE. AS FOR WHAT KIND OF TECHNOLOGIES NCATS COULD SUPPORT WITH THIS FUNDING, A FEW EXAMPLES. ALTERNATIVE DRUG DELIVERY MODALITIES SUCH AS NANOPARTICLE PACKAGING ARE AN IMPORTANT AREA OF RESEARCH NOW AND NCATS IS GOING TO BE HOSTING A WORKSHOP FOCUSED ON ALTERNATIVE DELIVERY MODALITIES IN MID-NOVEMBER. ANOTHER EXAMPLE WOULD BE IMPLANTS FOR MONITORING AND DELIVERING HIGHLY TUNED DOSES OF DRUGS BASED ON PATIENT'S BLOOD CHEMISTRY AND OF COURSE THOSE WHO HEARD ME TALK ABOUT OTHER PROJECTS KNOW THAT I FOCUS ON COMPUTATIONAL PROGRAMS AND SO COMPUTATIONAL ALGORITHMS TO HELP WITH DRUG DISCOVERY, TO PREDICT DANGEROUS INTERACTIONS BETWEEN DRUGS WOULD FIT WELL WITHIN NCATS'S MISSION AS WELL. NEXT SLIDE. WE HOPE TO OFFER A NEW OPPORTUNITY FOR FUNDING EXCITING EARLY-STAGE INVESTIGATOR INITIATED TECHNOLOGY TECHNOLOGY DEVELOPMENT LEADING TO TRANSFORMATIONAL TECHNOLOGIES LEADING TO SIGNIFICANT IMPROVEMENTS IN TRANSLATIONAL SCIENCE OUTCOMES AND TO PARTNERSHIPS WITH INDUSTRY LEADERS AND FASTER PIPELINES TO TRANSLATE TREATMENTS TO THE CLINIC. WITH THAT WE HAVE A FEW OF THE MORE TYPICAL QUESTIONS FOR COUNCIL MEMBERS, OF COURSE, BUT WOULD LIKE TO HEAR WHETHER THERE'S SPECIFIC FIELDS OF TECHNOLOGY DEVELOPMENT THAT WE SHOULD MAKE SURE TO INCLUDE IN AN EVENTUAL FUNDING ANNOUNCEMENT IF APPROVED. THANK YOU FOR YOUR TIME AND I'M HAPPY TO TAKE QUESTIONS. >> TYLER? >> YES, MARSHALL? >> ARE YOU COORDINATING WITH THE FDA ON HOW TO MAKE SURE THESE COULD BE USED IN CLINICAL TRIALS FOR THE THINGS YOU'RE FUNDING? >> SO, WE HADN'T TALKED MUCH ABOUT COORDINATING WITH THE FDA ON THIS, NO. BUT THAT IS DEFINITELY VERY INTERESTING, IT COULD BE A GOOD WAY TO MAKE SURE WE ARE FUNDING THINGS THAT ARE GOING TO GO THE DISTANCE AND NOT FLOUNDER EARLY ON. A GREAT SUGGESTION, DR. SUMMAR. >> ANDREW LOWE AND KEITH MUELLER ARE THE DISCUSSANTS. I WANTED TO GIVE ANDREW AND KEITH A SHOT AND GO TO RAJESH. >> THIS IS A GREAT PROPOSAL. AND DEFINITELY FILLS A NEED. I HAD A COUPLE QUESTIONS AND ONE SUGGESTION. SO, I GUESS ONE QUESTION IS, IS THE TECHNOLOGY THAT YOU'RE FOCUSING ON, DOES IT HAVE ANY PARTICULAR, YOU KNOW, GENERA? IS IT ENABLING TECHNOLOGIES OR IS IT EVERYTHING AND ANYTHING UNDER THE SUN? >> WE ENVISION A BROAD, OPEN OPTION BECAUSE THIS IS INVESTIGATOR INITIATED SO WE WANT TO FOCUS ON TECHNOLOGY DEVELOPMENT BUT OTHER THAN THAT JUST WITHIN THE TRANSLATIONAL SPACE I THINK IT WILL REALLY GIVE SOME OPENINGS FOR FUNDING THINGS THAT RIGHT NOW ARE VERY DIFFICULT TO FIND FUNDING FOR AS FAR AS SEED FUNDS GO. >> ONE AREA THAT I'M CURIOUS ABOUT, AND THIS IS THE COMMENT THAT IT HAS TO DO WITH CERTAIN TECHNOLOGIES THAT NOT ONLY ARE NOT BEING FUNDED RIGHT NOW BY THE PRIVATE SECTOR BUT ACTIVELY DISCOURAGED FOR A VARIETY OF INCENTIVE REASONS, I'VE BEEN INVOLVED IN A GROUP CALLED THE KIDNEY HEALTH INITIATIVE, AND ONE OF THE THINGS THAT HAS COME UP REPEATEDLY IS THE FACT THAT THERE IS TECHNOLOGY TODAY TO DEVELOP BASICALLY WHAT AMOUNTS TO ARTIFICIAL KIDNEY, AS OPPOSED TO DIALYSIS EVERY WEEK OR SO BUT THERE'S A STRONG ECONOMIC INCENTIVE TO KEEP THAT GOING BECAUSE THESE DIALYSIS TREATMENT CENTERS ARE VERY PROFITABLE. AND SO THE QUESTION IS WHETHER OR NOT THAT'S EXAMPLE OF TECHNOLOGY THAT THROUGH RFP OR SOME MECHANISM WHERE YOU CAN EMPHASIZE A DESIRE TO FUND CERTAIN TECHNOLOGIES THAT CAN BE TRANSFORMATIVE FOR PATIENT HEALTH THAT MAY NOT HAVE THE SAME KIND OF ECONOMIC INCENTIVES THAT WOULD BE REALLY HELPFUL. AND RELATED COMMENT, IS THAT THERE ARE OTHER ORGANIZATIONS THAT I THINK WOULD BE INTERESTING TO CONNECT WITH AND POSSIBLY PARTNER WITH. NCATS PROVIDES VALUABLE FINANCING BUT I'M THINKING OF THE WELLCOME TRUST AND THE PROGRAM CALLED WELLCOME, ON THE SAME LINES OF MEDICAL TECHNOLOGY, SO I WONDER WHETHER OR NOT THE IMPACT CAN BE MAGNIFIED BY COORDINATING COLLABORATING WITH SOME OF THESE NON-PROFIT GROUPS. >> WE WANT TO FOCUS ON TECHNOLOGIES THAT LEAD TO TRANSLATIONAL IMPROVEMENTS SO I THINK THE EXAMPLE YOU GAVE OF THE KIDNEY, YOU KNOW, THAT'S A GREAT EXAMPLE OF SOMETHING WE COULD FUND. I DON'T KNOW YET HOW MUCH WE WANT TO FOCUS ON, YOU KNOW, SOLICITING FOR SPECIFIC IDEAS BECAUSE ONE OF THE REASONS THAT WE HAVE FOCUSED AS A BROAD INITIATIVE THAT WORKED WELL FOR NIDA WITH THE CBRA INITIATIVE HAVING A BROAD OPEN CALL FOR THIS KIND OF FUNDING BUT IN THE BASIC SCIENCE SPACE BUT IT'S A REALLY GOOD POINT AND WE'LL TALK MORE ABOUT HOW WE MIGHT BE ABLE TO MAKE SURE THAT WE GET SOME OF THOSE IDEAS INTO THE PROGRAM. >> THANK YOU. KEITH IS IN A NOISY ENVIRONMENT SO I'LL RELAY HIS MESSAGE. YOU CAN SEE IT IN THE CHAT TOO. HE SUPPORTS THE SEED FUNDING INCLUDING THIS CONCEPT AND ADMITS TO HAVING TO THINK ABOUT TECHNOLOGY, QUOTE, DIFFERENTLY IN THE REALM OF SOFTWARE DEVELOPMENT. BUT THE DESCRIPTION PROVIDED HELPED HIM UNDERSTAND THE CONTEXT OF THE TERM SO HE'S SUPPORTIVE AND EXAMPLES IN THE PRESENTATION WERE WHAT HE WANTED TO SEE AND SOFTWARE DEVELOPMENT SHOULD BE INCLUDED AS WELL. HE HAD A SIMILAR QUESTION, THAT WAS COVERED AS WELL. HE ALSO NOTES THAT TECHNOLOGY THAT HELPS WITH DISSEMINATION AND ADOPTION, USE OF SOFTWARE AND PLATFORMS ARE EXAMPLES, WOULD BE RESPONSIVE TO THE PREVIOUS DISCUSSION. >> ABSOLUTELY TRUE. WE EXPECT THAT DEVELOPMENT OF SOFTWARE TOOLS COULD FIT WITHIN THIS SPACE AS WELL, AND SO AGAIN I HOPE THAT WE CAN END UP WITH A GOOD BROAD SWATH OF DIFFERENT TYPES OF TECHNOLOGIES WE'RE ABLE TO FUND THROUGH THIS, INCLUDING SOFTWARE TOOLS FOR SURE. >> RAJESH? >> TWO QUESTIONS, CONCERNS, COMMENTS, YOU CAN ADDRESS THEM. IN SOMETHING LIKE THIS THAT YOU BASICALLY SORT OF ARE INVITING ANYTHING UNDER THE SUN, I MEAN, HOW WILL REVIEW HANDLE THIS? I'M TRYING TO FIGURE OUT HOW YOU WOULD EVEN BE ABLE TO COMPARE APPLES TO ORANGES TO PAERS TO WHATEVER ELSE MIGHT COME THROUGH THE SYSTEM? ALSO REVIEW RELATED FOR ME, YOUR PREMISE IS ALSO OFTEN DIFFICULT TO FIND FUNDING FOR THESE IDEAS AND THE REASON BEING IT'S GREEN FIELD. HOW ARE YOU GOING TO ENSURE THAT SOMEBODY SAYS WHERE IS THE PRELIMINARY DATA, WHERE SHOULD SHOWN PROOF OF PRINCIPLE, AND EVERY QUESTION THE ANSWER SHOULD BE NO IF IT'S TRULY INNOVATIVE. THE IDEA HAS TO BREAK NEW GROUND. IN AN NIH REVIEW PERSPECTIVE HOW ARE YOU GOING TO HANDLE THAT? >> REALLY GOOD POINT. I SPOKE TO AMY LOSSY FROM NIDA, ON THE CALL WITH HER, I'LL HAND OFF TO HER AFTER I TRY TO FIELD THE QUESTION. I SPOKE TO HER ABOUT THINGS THEY HAVE DONE RIGHT AND ISSUES THEY'VE HAD COMING UP WITH THE CBER PROJECT, ONE OF THE MAJOR QUESTIONS FOR HER, FOR US, THAT OF REVIEW. THE REVIEW CAN BE DIFFICULT BECAUSE IT IS VERY BROAD RANGING AND I THINK THE FIRST THING THAT WE WOULD WANT TO DO IS REALLY TRY TO SEEK OUT A GROUP OF REVIEWERS WHO ARE COMFORTABLE THINKING AT A VERY SORT OF HIGH LEVEL, YOU KNOW, BROAD RANGE LEVEL ACROSS TRANSLATIONAL SCIENCE AND SEE IF WE CAN HAVE THOSE REVIEWERS HANDLE, YOU KNOW, A SET OF THE APPLICATIONS ALL TOGETHER AS OPPOSED TO SEEKING OUT REVIEWERS FOR EACH APPLICATION INDIVIDUALLY, HOPEFULLY HAVE REVIEWERS THAT CAN SORT OF SEE THE FIELD AT THE TIME. IT DOES REVIEWERS THAT CAN THINK OF THE HIGH LEVEL BROAD TRANSLATIONAL SCIENCE. AMY, WOULD YOU GIVE A QUICK -- SURE >> -- DISCUSSION OF HOW YOUR REVIEW WORKS? >> YES, IT CAN BE CHALLENGING, WE HAVE EVERYTHING FROM NEW PILL POCKET TO LIKE NANOBASKET TO ENCAPSULATE A DRUG TO SINGLE CELL TECHNOLOGIES COMING OUT. THEY ARE ALL DONE IN THE SAME REVIEW, IN HOUSE. OUR SRO DOES A GOOD JOB FINDING PEOPLE WITH EXPERTISE ACROSS THESE VARIABLES, AND EACH ROUND IS A DIFFERENT SET OF VARIABLES, SO THERE'S A LOT OF LEG WORK ON OUR REVIEW STAFF TO DO THAT BUT IT COMES DOWN TO EDUCATE REG VIEW. WE MAKE IT CLEAR THIS IS AN R21 ON STEROIDS, 80% OF WHAT WE FUND WORKS WE'VE FAILED. WE ONLY WANT 50% OF THESE PROJECTS TO BE SUCCESSFUL. WE'VE TALKED TO THEM ABOUT STRESSING INNOVATION, THAT'S THE MOST IMPORTANT PART OF THIS. WE CAN CHANGE THE REVIEW QUESTION, GIVE SPECIAL INSTRUCTIONS TO REVIEWERS, CONSIDERED SAYING PRELIMINARY DATA BUT WE DID NOT -- DECIDED NOT TO DO THAT BECAUSE WE THOUGHT IT WOULD ACTUALLY BE DETRIMENTAL. I THINK IT'S BEEN A REALLY PRODUCTIVE, YOU KNOW, PROGRAM. WE'VE HAD IN PLACE FOR ALMOST 20 YEARS AND GET A NEW ITERATION EVERY TIME. IT CAN WORK. IT'S HAVING GOOD DIALOGUE BETWEEN PROGRAM AN REVIEW AND GOOD CHAIR WHO REALLY UNDERSTANDS THE PROGRAM. >> I GUESS WHAT YOU WERE SAYING EVEN IF 50% DON'T WORK AFTER TWO YEARS YOU CONSIDER THAT A SUCCESS, IS THAT WHAT YOU HEARD? >> ABSOLUTELY. >> I THINK THAT'S TOO HIGH. >> IT COULD BE. MAYBE 20% WORK. BUT 50% SCARES REVIEW, RIGHT? I TELL REVIEWERS, WE WANT TO FUND STUFF THAT'S ON THE LEADING EDGE WITH A GREAT CONCEPT THAT IF THIS WORKS THIS IS GOING TO TRANSFORM HOW WE -- >> YOU NEED ONE IN TEN IDEA TO WORK, IN MY OPINION. THAT'S WHERE YOU WANT TO GO HERE. I WOULD RAISE THE BAR. >> THANK YOU. WE APPRECIATE IT. >> THANKS FOR THE QUESTION, RAJESH. I WANT TO MAKE SURE YOU KNOW A LOT ABOUT REVIEW. DID YOU WANT TO COMMENT ON THAT PIECE AS WELL BEFORE I TURN IT OVER TO PAUL? >> I WAS PUTTING ON MY DEA DIRECTOR HAT TO RESPOND, TO ASSURE RAJESH WE HAVE ABILITY APPLES TO APPLES, TO GIVE AMPLE CONSIDERATION, THE THING I BELIEVE OUR STAFF WOULD LOOK FORWARD TO DO, A CHALLENGE THAT PROVIDES INTELLECTUAL FOOD AND HAS BEEN DONE ACROSS THE NIH AND I'M CONFIDENT WE WOULDN'T HAVE ANY ISSUES TAKING CARE OF THIS APPROPRIATELY. THAT'S IT. >> THANK YOU, ANNA. >> PAUL? >> WHAT REQUIREMENTS ARE OR WILL BE IN PLACE FOR THE PROPOSALS TO INCLUDE CONTINUATION PLAN OR NEXT STEPS DISSEMINATION PLAN SHOULD THEY BE SUCCESSFUL? >> WE WANT TO INCLUDE A FOLLOW-UP BECAUSE WE WOULD LIKE TO SEE THESE LEAD TO ADDITIONAL FUNDING, SBIRs AND STTRs WOULD BE FANTASTIC. ONE OF OUR GAUGES IS HOW MUCH THIS SEED FUNDING LEADS TO ADDITIONAL FUNDING. SO I THINK WE WILL DEFINITELY ASK THEM FOR INFORMATION ON THEIR PLANS FOR MOVING FORWARD AND DO FOLLOW-UP TO TRY TO SEE HOW SUCCESSFUL EACH OF THESE AWARDS WERE. >> GREAT, THANKS. >> ARE YOU GOING TO PUT TOGETHER A SHOWCASE FOR THESE THINGS? BOTH -- TO SPARK THE LIFESPAN FOR THESE THINGS? >> THAT'S SOMETHING WE CAN DEFINITELY LOOK INTO. THANK YOU SO MUCH. >> THAT'S WHY YOU KEEP ME AROUND. [LAUGHTER] >> AND DR. KRESLER? >> TO ITERATE WHAT WAS SAID EARLIER, THERE'S A LOT OF SEED FUNDING AVAILABLE FOR IDEAS WITH 10% CHANCE OF SUCCESS, IF THEY HAVE COMMERCIAL RUNWAY DOWN THE ROAD, AND YOU MIGHT BE ABLE TO ADDRESS THE GAP IN THAT COMMERCIAL RUNWAY FURTHER AWAY, BEING INTELLIGENT WHERE YOU INVEST IS LIMITED BUT STILL CRITICAL FUNDING IN AREAS WHERE WILL NOT BE INVESTED, HHR AND ASN DEVELOPED TOGETHER, AND HAS BEEN QUITE SUCCESSFUL SO STRATEGICALLY IDENTIFY AN AREA OF LIMITED ACCESS TO SEED FUNDING MIGHT BE SOMETHING TO CONSIDER AS WELL. >> YOU'RE SAYING BUILT INTO THE REVIEW A SORT OF QUESTION OF HOW LIKELY IT IS THAT THIS WOULD BE FUNDED WITHOUT THE SEED FUNDING? >> EXACTLY. KIND OF MEASURE OF UNMET NEED. >> MEASURE OF NEED, YEAH. >> SIGNIFICANT. AND OBVIOUSLY IF SUCH AN ACTIVITY GETS YOUR STAMP OF APPROVAL, THEY MIGHT ACTUALLY BE IN A MUCH STRONGER POSITION TO THEN SUBSEQUENTLY ACQUIRE FUNDING, A PHENOMENON IN SBIR WHICH WE'RE WELL AWARE. >> EXCELLENT IDEA. THANK YOU. >> I WOULD JUST SAY, TYLER, WHAT YOU'RE DOING IS SO IMPORTANT RIGHT NOW AS WE'VE ENTERED INTO A WORLD OF CAUTIOUS CAPITAL, SO HARD FOR THE EARLY STAGE COMPANIES TO GET BC FUNDING ON REASONABLE TERMS RIGHT NOW. AND THIS IS REALLY GOING TO PLAY AN IMPORTANT ROLE IN THE NEXT TWO YEARS AS OUR ECONOMY IS GOING THROUGH A CHALLENGING TIME. IT'S VERY EASY FOR A DE-RISKED COMPANY TO RAISE FUNDING, BUT EVEN THEY ARE HAVING A HARDER TIME THAN THEY USED TO. I'M DELIGHTED TO SEE YOU'RE LEADING THIS. >> THANK YOU SO MUCH. I APPRECIATE IT. >> HENCE THE NAME, ASCETTS. >> YES. >> THAT WAS ALL CHRISTINE, I'M NOT SURE, WAS THAT YOU? >> I FEAR IT MIGHT HAVE BEEN ME. >> IT WAS A COLLABORATION BETWEEN CHRISTINE AND I, WE WENT BACK AND FORTH. I'M NOT A HUGE FAN OF LONG ACRONYMS BUT I WAS HAPPY WITH THIS ONE BY THE TIME WE WORKED IT OUT. >> I DON'T WANT TO KNOW HOW MUCH TIME WAS SPENT ON THAT. IT'S A GOOD ONE. I COMPLETELY AGREE. >> ANNA, WE'VE GONE THROUGH THE QUESTIONS, WOULD YOU START THE MOTION PROCESS? >> IF THERE'S NO FURTHER DISCUSSION, COULD WE HAVE A MOTION TO APPROVE THE CONCEPT? >> SO MOVED. >> SECOND. >> SECOND. >> ALL IN FAVOR? >> AYE. >> AYE. >> AYE. >> AYE. >> ANY OPPOSED? ANY ABSTENTIONS? WITH THAT THE CONCEPT IS APPROVED. THANK YOU VERY MUCH. >> THANK YOU VERY MUCH. WE APPRECIATE IT. >> THANK YOU. AND WE HAVE A LITTLE BIT OF WORK TO DO TO FINALIZE AND INCORPORATE THESE COMMENTS. OKAY. ON TO THE NEXT COUPLE TOPICS, THESE ARE SBIR/STTR PROGRAMS, SO DR. LILI PORTILLA WILL GIVE AN OVERVIEW AND DR. TAGLE WILL PRESENT CONCEPTS I BELIEVE. TAKE IT AWAY, LILI. >> I'LL BE GIVING BACKGROUND ON SBIR, STTR, AS THESE NEXT CONCEPTS WILL BE UTILIZING THOSE MECHANISMS. CONGRESSIONALLY MANDATED PROGRAM, 3.2 SET ASIDE FOR SBIR AND .45 FOR STTR AND BY THE WAY IN THE NEWS YESTERDAY THE PROGRAM WILL GET REAUTHORIZED FOR NEXT YEAR, VERY EXCITING. NEXT SLIDE PLEASE. AND THERE ARE SEVERAL FUNDING MECHANISMS WITHIN THE STTR, MOST OF THE APPLICATIONS FOR THE NIH COME IN THROUGH THE OMNIBUS SOLICITATION WHICH COVERS 24 PARTICIPATING INSTITUTES, ALONG WITH OUR SISTER AGENCIES OF THE CDC AND FDA WITH TOP INCORPORATION UNDER THE OMNIBUS. WHAT WE'RE TALKING ABOUT HERE ARE TARGETED GRANT SOLICITATIONS WHICH EXIST UNDER THE SBIR PROGRAM. THERE'S ALSO BEEN OTHER OPPORTUNITIES THAT COUNCIL HAS CLEARED USING THE CONTRACT SOLICITATION MECHANISM. WHICH IS ONLY ONCE A YEAR THAT MECHANISM IS PUT OUT, THAT SOLICITATION IS PUT OUT FOR SBIR COMPANIES TO APPLY TO SPECIFIC TOPICS. THE BENEFITS ARE SEVERAL, LINKED TO OVERALL BUDGET, MAYBE WITH EXCEPTION OF THIS PAST -- WITH THE PROGRAM WAITING TO LAST MINUTE TO GET REAUTHORIZED, BUT TYPICALLY IT'S STABLE AND FUNDS DO NOT HAVE TO BE REPAID SO IT'S A GOOD SOURCE OF NON-DILUTED FUNDING THAT THE GOVERNMENT PROVIDES AND I.P. RIGHTS ARE RETAINED BY THE SMALL BUSINESS, AND ONCE YOU'RE IN, TECHNICAL ASSISTANCE CAN BE PROVIDED BY THE NIH WITH VARIOUS PROGRAMS AND INITIATIVES. AND ALL PROJECTS UNDERGO RIGOROUS SCIENTIFIC PEER REVIEW PROCESS. I'VE HEARD MENTIONED TIGHTENING OF PRIVATE EQUITY FUNDING UNDER THE CURRENT -- POTENTIALLY THE ECONOMIC PICTURE IN THE U.S. AND I WOULD IMAGINE THAT OVER THIS NEXT YEAR WE'RE GOING TO SEE INCREASE OF APPLICATIONS COMING IN BECAUSE OF THAT VERY FACT AND THIS IS EXACTLY THE VOID THAT THIS PARTICULAR PROGRAM IS SUPPOSED TO FILL. NEXT SLIDE. THREE PHASES, FIRST IS FEASIBILITY STUDIES WITH PROJECTS LASTING 6 TO 12 MONTHS, THERE'S BUDGETARY GUIDELINES AS WELL PHASE 1 AND FOR PHASE 2 IT'S MORE RESEARCH R&D, PROJECTS CAN LAST BETWEEN 2 TO 3 YEARS, COMBINED MECHANISMS IS A FAST TRACK WHICH IS THE PHASE 1 AND PHASE 2, BENEFIT -- HAVING BENEFIT OF ONE REVIEW AS LONG AS YOU MEET THE SPECIFIC AIMS FOR THE PHASE 1, YOU CAN CONVERT EASILY TO PHASE 2 WITHOUT GOING TO REVIEW. THERE'S ANOTHER MECHANISM IS DIRECT TO PHASE 2 WHICH ALLOWS YOU TO SKIP PHASE 1, UNDER THE PRESUMPTION YOU HAVE FEASIBILITY DATA YOU'VE GOTTEN THROUGH ANOTHER SOURCE. THERE'S PHASE 2 COMPETING RENEWALS AS WELL, THAT WE PARTICIPATE IN. PHASE 3 IS COMMERCIALIZATION GRADUATION OF THE PROGRAM, APPLICANTS UNDERSTAND IN THE CASE OF NIH WE'RE NOT GENERALLY THE CUSTOMER FOR THE PRODUCT. SO HERE'S WHERE WE CONSIDER THEM PARTNERING, DEVELOPING STRATEGIC RELATIONSHIP, FINDING EXIT STRATEGY FOR OUTSIDE FUNDING OUT OF THE PROGRAM. THE DIFFERENCE BETWEEN CONTRACT AND GRANT, SOLICITATION FOR CONTRACT IS ONCE A YEAR, IN FACT IT'S ABOUT TO CLOSE AT THE END OF OCTOBER FOR THE CURRENT ROUND OF TOPICS THAT EXIST. AND THE LOCUS OF REVIEW IS WITH NCATS, FOR MOST OF OUR GRANT PROGRAMS, THE LOCUS OF REVIEW IS WITH THE CENTER FOR SCIENTIFIC REVIEW, OCCASIONALLY NCATS DOES REVIEW SOME OF THE GRANTS, DEPENDING ON MECHANISMS AS WELL. AND THERE MAY BE MULTIPLE SUBMISSION DATES AS A RESULT OF THAT, OF THE GRANTS. OKAY. NEXT SLIDE. NOW DAN, I WILL HAND IT TO YOU TO DIVE IN AND DISCUSS THE SPECIFIC CONCEPTS. >> THANK YOU, LILI. GOOD AFTERNOON, EVERYONE. SO THIS IS A CONCEPT CLEARANCE FOR COMING OUT OF THE OFFICE OF SPECIAL INITIATIVES, AND CERTAINLY THANK YOU TO LILI FOR GIVING THE OVERVIEW OF OFFICE OF STRATEGIC ALLIANCE ON THE SMALL BUSINESS PROGRAM, THE TWO CONCEPTS ARE COLLABORATION WITHIN OSA AND OSI. I GAVE AN OVERVIEW OF THE OFFICE LAST MAY COUNCIL SO I'M GOING TO GO BRIEFLY, SO OUR OFFICE ESSENTIALLY ADDRESSES TRANSLATIONAL PROGRESS BY DEVELOPING DISRUPTIVE TECHNOLOGIES. IF YOU CLICK ON THE NEXT ANIMATION. I'M GOING TO TALK ABOUT TWO CONCEPTS, ONE RELATED TO AUTOMATED CHEMISTRY, SECOND RELATED TO TISSUE CHIPS PROGRAM FOR DRUG SCREENING. IN TERMS OF THE FIRST ONE, THIS IS CALLED MINIATURIZATION AND AUTOMATION OF TISSUE CHIP SYSTEMS, AND SO THIS IS COMING OUT OF THE TISSUE CHIP PROGRAM. AND SO JUST TO GIVE A BRIEF BACKGROUND, JONI ALREADY TALKED ABOUT IT IN HER DIRECTOR'S REPORT, THIS MORNING, IN TERMS OF TISSUE CHIPS IN SPACE BEING LAUNCHED IN JULY AND SO IT'S BEEN AN ONGOING COLLABORATION WITH NASA. AND INTERNATIONAL SPACE STATION, A NUMBER OF EXCITING PROJECTS WE'RE LEARNING IN TERMS OF THE SCIENCE AND BIOLOGY OF AGING BUT THERE'S BEEN TREMENDOUS IMPROVEMENT IN HOW WE APPROACH INSTRUMENTATION THAT SUPPORTS TISSUE CHIPS. AND AS JUST TO GIVE ADDITIONAL BACKGROUND, TISSUE CHIPS HAS BEEN LARGELY SUCCESSFUL POSITIONED AS NEW ALTERNATIVES METHODS FOR DRUG DEVELOPMENT AND IT'S BEING WIDELY USED. BUT IT'S STILL NOT TO THE POINT THAT IT'S -- THERE'S WIDESPREAD ADOPTION BY INDUSTRY, BY REGULATORY AGENCIES, AND BY BIOMEDICAL RESEARCH IN GENERAL. AND THE MAIN COMPONENT THAT MAKES IT HARD FOR ADAPTERS TO USE THIS IS THAT ESSENTIALLY COMPLEXITY OF THE SUPPORTING INSTRUMENTATION, WHETHER IT BE THE INSTRUMENTATION THAT REQUIRES BIOMEDICAL ENGINEERS, MICROFLUIDICS EXPERTS, AND SO ON. SO WITH THE COLLABORATION WITH NASA, AND CENTER FOR ADVANCEMENT OF SCIENCE IN SPACE AND TISSUE CHIPS PROGRAM I THINK WE HAVE LEARNED VALUABLE LESSONS HOW TO AUTOMATE AND MAKE THIS INTO A MINIATURIZED PLATFORM. JUST TO GIVE YOU AN ILLUSTRATION AND I SHOWED THIS AT THE MAY COUNCIL, CLICK ON THE NEXT ANIMATION PLEASE. SO IN THE TYPICAL EXPERIMENT 24 KIDNEY CHIPS, REQUIRES CONTRAPTION ABOUT THE SIZE OF AN AVERAGE KITCHEN REFRIGERATOR, ABOUT 48 CUBIC FEET. AND CAN YOU KEEP ON CLICKING PLEASE. AND CERTAINLY IN THE BEGINNING OF THE PROGRAM BACK IN 2018 OUR CONVERSATION WITH SpaceX, WITH NASA, PUTS A PREMIUM IN TERMS OF PAYLOAD SO THEY PROVIDED US WITH PAYLOAD DEVELOPERS AND SPACE IMPLEMENTATION PARTNERS AND THROUGH THE COLLABORATIONS WITH THEM WE WERE ABLE TO MEET THE DEMAND OF SpaceX AND NASA, THAT A 48-CUBIC FOOT INSTRUMENTATION BE REDUCED TO 1.6 CUBIC FEET, ABOUT THE SIZE OF A SHOE BOX, GOING FROM REFRIGERATOR TO SHOE WAS ACHIEVED WITH SPACE IMPLEMENTATION PARTNERS, TAKING LESSONS LEARNED AND BEING ABLE TO DEPLOY THAT FOR HOW WE USE TISSUE CHIPS FOR BIOMEDICAL RESEARCH HERE ON EARTH. NEXT SLIDE PLEASE. OUR OBJECTIVE TO TRANSLATE LESSONS LEARNED, IN THE TISSUE CHIPS IN SPACE PROGRAM, AND BEING ABLE TO INCREASE COMMERCIALIZATION POTENTIAL OF TISSUE CHIP PLATFORMS, AND OF COURSE WIDESPREAD USE IN DRUG DEVELOPMENT LEADING TO BETTER THERAPEUTICS IN TERMS OF SAFER AND MORE EFFECTIVE CANDIDATE DRUGS. SO NEXT SLIDE PLEASE. THE KEY AREAS WE WANT TO EMPHASIZE WOULD BE CREATION OF BENCH-TOP MODEL THAT IS PORTABLE AND SELF-CONTAINED SYSTEM THAT MAINTAINS 3D TISSUE CONSTRUCTS OR ARCHITECTURE MEANING HAVING PRECISE THERMAL CONTROL, FLUID PUMPING, SAMPLING, BIOLOGICALLY RELEVANT OUTPUTS OF TISSUE HEALTH AND FUNCTION SUCH AS FLUID SAMPLING, ELECTRODE INCORPORATION, MICRO-- OR BIOSENSING. SO THIS IS ALL DONE AUTOMATICALLY. ALSO, KEY AREA TO EMPHASIZE IS THAT THIS SHOULD LEAD TO CLEAR COMMERCIALIZATION PATHWAY. IN TERMS OF IMPLEMENTATION AND IMPACT, USING THE SBIR/STTR, AND WE WANTED TO CONTINUE TO USE TISSUE CHIPS AS REALLY A PROMISING TRANSLATIONAL TOOL FOR DRUG DEVELOPMENT AND WHAT WE EXPECT FOR THIS IS TO INCREASE CERTAINLY THE USE AND CONSUMPTION OF TISSUE CHIP TECHNOLOGY AND DRUG DEVELOPMENT. I THINK THIS YEAR TISSUE CHIP COMMERCIAL AREAS IS $80 MILLION, THAT IS EXPECTED TO GROW BY 2029 EVEN WITH JUST CURRENT TECHNOLOGY TO $300 MILLION. LARGELY INDUSTRY BEING THE MAJOR END USERS. WE HAVE A POTENTIAL TO NOT ONLY EXPAND THE USE BUT ALSO THIS TECHNOLOGY IN DRUG DEVELOPMENT BUT ALSO IN TERMS OF ITS COMMERCIAL POTENTIAL. SO NEXT SLIDE PLEASE. AND SO WHAT WOULD SUCCESS LOOK LIKE? IT WILL RESULT IN AUTOMATED TISSUE CHIP PLATFORM WITH SMALLER AND SIMPLER FOOTPRINT FOR USE BEYOND DRUG DEVELOPMENT ACROSS MULTIPLE APPLICATIONS SUCH AS IN PERSONALIZED PATIENT-SPECIFIC CHIPS, USE BY DEFENSE INDUSTRY IN TERMS OF BATTLEFIELD ASSESSMENT FOR COUNTERMEASURES AGAINST EVALUATING THREATS, LONG-TERM STRESSORS INCLUDING DISEASE, SPACE FLIGHT, OTHER POTENTIAL USES. AND SO IN SUMMARY, THIS CONCEPT AIMS TO TRANSLATE LESSONS LEARNED FROM TISSUE CHIPS IN SPACE PROGRAM IN TERMS OF REENGINEERING TISSUE CHIP PLATFORMS AND INSTRUMENTATION TO MINIATURIZATION AND AUTOMATION AND EASE OF USE, EXPECTED TO ACCELERATE USE THROUGH COMMERCIALIZATION OF IMPROVED PLATFORMS, AND THEN LAST SLIDE SHOULD BE OUR TYPICAL -- CLICK ON THE LAST SLIDE PLEASE -- OUR TYPICAL QUESTIONS FOR COUNCIL MEMBERS IN TERMS OF WHAT COULD IMPROVE THIS INITIATIVE AND WHAT ARE THE KEY POINTS TO CONSIDER AND THEN SPECIFICALLY OTHER KEY PARTNERS WE NEED TO ENGAGE SINCE WE HAVE ALREADY QUITE AN INVESTMENT IN THIS FIELD. AND AT THIS POINT I'D WELCOME QUESTIONS FROM COUNCIL MEMBERS AND WELCOME OUR TWO STAFF PANELISTS, DR. GRIMES PROGRAM OFFICER IN THE TISSUE CHIPS PROGRAM AND DR. FERRER, DIRECTORY OF THE 3D BIOPRINTING LABORATORY AT NCATS INTRAMURAL DIVISION OF PRE-CLINICAL INNOVATION. THANK YOU AND HAPPY TO ANSWER ANY QUESTIONS. >> GREAT. THANK YOU, DAN. AND WE HAVE TWO DISCUSSANTS, SO MATTIAS WOULD YOU LIKE TO GO FIRST? >> FIRST I HAVE TO DECLARE I HAVE BEEN INVESTIGATOR FROM TISSUE CHIP PLATFORM, A DOCTOR FROM SEATTLE, I HAVE BEEN ON THE ACTION PHASE AND WANT TO ENDORSE WHAT I MENTIONED AT THE SIGNIFICANT INPUT OF KIDNEY IN SPACE PROGRAM FOR OUR PROGRAM WAS THAT WERE ABLE TO STREAM LINE USABILITY OF THE PLATFORMS IN A WAY WHICH WE WOULD NOT HAVE EXPECTED TO ACHIEVE EVER WITHOUT THAT FUNDING EFFORT. JUST AN ENDORSEMENT OF THE OVERALL CONCEPT AND IT'S CLEAR THAT USE OF THE CLINICAL CHIP PLATFORMS IS STILL NOT WHERE IT SHOULD BE AND ONE OF THE MAIN REASONS IS COMPLEXITY IN TRANSFERRING THAT TECHNOLOGY TO STAKEHOLDERS, SO THAT'S WHERE THIS IS VERY TIMELY, A CLEAR OPPORTUNITY FOR SIGNIFICANT COMMERCIAL DEVELOPMENT, STRONG ENDORSEMENT FROM THAT AREA. CLEARLY CUSTOMMABILITY, PHARMACEUTICAL ENTITIES, I WOULD ALSO EXPECT IT AS A SIGNIFICANT MARKER IN ACADEMIC ARENA RIGHT NOW THAT TECHNOLOGIES ARE DIFFICULT TO TRANSFER, THREE FULL-TIME FTE IN MY LAB WHO MAINTAIN KIDNEY ON A CHIP, THIS COULD RESULT IN SIGNIFICANT COST SAVINGS OF THE PLATFORMS. I LIKE THE CHALLENGE TO US, WHAT ARE ADDITIONAL FUNDING OPPORTUNITIES, KEY PARTNERS TO ENGAGE, AND THINKING OUTSIDE OF THE BOX BATTLEFIELD ACTIVITY IS CLEARLY BIOSTATS POTENTIAL TO INTERACT WITH DoD, BARDA IS A POTENTIAL OPPORTUNITY, I'M NOT SURE IF YOU'RE AWARE ASPR HAS BEEN ELEVATED TO ADMINISTRATION FOR REPURPOSING, FOR BIODEFENSE, AND HAVE PROGRAM UNDER DEVELOPMENT WHERE PORTABLE BIOSENSOR UNIT MIGHT ACTUALLY VERY WELL ALIGN WITH SOME OF THE GOALS SO IF YOU'RE NOT ALREADY IN CONTACT THOSE MIGHT BE TWO ENTITIES TO SEE IF THAT WOULD FIT INTO CURRENTLY DEVELOPING EFFORTS. >> THANK YOU, MATTIAS. WE HAVE BEEN IN TOUCH WITH BARDA AND ASPR, THROUGH THE I-DRIVE PROGRAM SO WE'VE BEEN IN CONVERSATIONS AND HAVE BEEN IN PARTNERSHIP WITH THEM IN SOME TISSUE CHIP-RELATED ACTIVITIES AS WELL. >> RAJESH? >> I DON'T HAVE MUCH. THIS IS GREAT. I THINK YOU'RE USING RIGHT MECHANISM TO GET TO THE APPROPRIATE ENDPOINT, SO ONE WOULD HOPE PEOPLE WILL TAKE ON THE CHALLENGE AND MAKE IT HAPPEN. THE ONE ADDITIONAL AREA THAT CAME TO MIND, CONTINUES ON WITH THE LAST THING MATTIAS SAID IN THE CONTEXT OF BIOSENSORS OR THINGS ON THE DIAGNOSTIC SIDE, AND IN PRINCIPLE ONE OF THE THINGS YOU MIGHT THINK ABOUT MAYBE IT'S TOO MUCH TO REACH IN THIS ROUND OR MAYBE IT'S SOMETHING THAT'S SEPARATE, ONE OF THE CHALLENGES THAT ONE HAS IN AREAS THAT ARE MORE REMOTE AND NOT EASY TO HAVE LIKE ELECTRICITY GRIDS AND WHAT NOT TO HAVE SOME -- TO HAVE MACHINES THAT DON'T -- ARE NOT POWER HUNGRY OR CAN WORK ON SOLAR, FOR EXAMPLE. SO SOMETHING THAT ESSENTIALLY ALLOWS A KIT TO BE DEPLOYED IN A DESERT OR SOMEWHERE IN THE JUNGLE OR WHEREVER YOU MIGHT BE AND SO IT CHANGES WHAT CAN HAPPEN FROM DIAGNOSTIC PERSPECTIVE ESPECIALLY IN THE CONTEXT OF FOR INSTANCE BRINGING INFECTIOUS DISEASE ANGLE, IF YOU'RE THINKING ABOUT HOW TO DO SOME OF THESE THINGS IN A QUICK AND CHEAP WAY BUT IT'S DONE IN THE FIELD SO THE FIELD USE OF IT IN NON-INDUSTRIALIZED ARENAS IS SOMETHING TO THINK ABOUT. >> GREAT. THANK YOU, THAT'S A GREAT SUGGESTION. WE HAVE ACTUALLY HAD SUCH PRODUCTIVE CONVERSATIONS WITH PEOPLE AT ACTION SPACE, WHICH IS IN CHARGE BY NASA TO DEVELOP THE NEXT GENERATION INTERNATIONAL SPACE STATION. ESPECIALLY LOOKING AT RESOURCE-POOR FACILITIES WHERE, YOU KNOW, YOU WOULD THINK THAT INTERNATIONAL SPACE STATION IS NOT NECESSARILY RESOURCE POOR BUT THEY ARE VERY LIMITED IN TERMS OF SPACE EVEN COOLING, HEATING, AND POWER SUPPLIES AS WELL. YEAH, SO DEVELOPING SUCH MODULAR PLATFORMS THAT WOULD ADDRESS THOSE NEEDS ARE SOMETHING THAT'S REALLY AT THE TOP OF OUR LIST AS WELL BUT, AGAIN, WORKING WITH NASA AND THE COMMERCIAL SPACE STATION DEVELOPERS AT THIS POINT. >> ONE GROUP THAT THINKS ABOUT THIS IN MORE SYSTEMATIC WAY IN TERMS OF DEPLOYMENT IN THE AFRICAN CONTENT IS THE GATES FOUNDATION. YOU KNOW, DAN WHO USED TO BE PART OF THE DARPA GROUP AND WENT THERE MIGHT BE SOMEONE YOU WANT TO REACH OUT TO. >> OKAY. I'LL WRITE THAT DOWN. THANK YOU SO MUCH. >> I LIKE THE TIE-IN OF THE BIOSENSOR AS WELL FOR THE DIAGNOSTIC SIDE. GREAT COMMENT. ANDREW? >> SO I THINK THIS IS A WONDERFUL INITIATIVE AND EXAMPLE OF AN AREA THAT WOULD PROBABLY NOT HAVE MADE NEARLY AS MUCH PROGRESS IF IT HADN'T BEEN FOR NCATS, SUSTAINED EFFORT OVER THE YEARS TO FOCUS ON TISSUE CHIPS. SO I'VE GOT -- I'M FULLY SUPPORTIVE OF MINIATUREIZATION AND IMPROVEMENT IN TECHNOLOGY BUT A COUPLE QUESTIONS OR SUGGESTIONS HOW TISSUE CHIPS COULD BE MADE MORE RELEVANT FOR TRANSLATION SPECIFICALLY WITH RESPECT TO DRUG DEVELOPMENT. SO, ONE THING I FIND SURPRISING IS THAT TISSUE CHIPS AREN'T USED MORE OFTEN IN PRE-CLINICAL WORK AND AS PART OF A SUBMISSION FOR AN IND. I'M NOT SURE WHY THAT IS BECAUSE I KNOW THAT THERE'S SOME ANECDOTAL EVIDENCE OUT THERE THAT TISSUE CHIP STUDIES ARE OFTEN MORE PREDICTIVE FOR HUMAN TOX THAN MOUSE MODELS BUT I DON'T KNOW IF THAT'S BEEN FULLY DOCUMENTED ACROSS DISEASES AND THERAPEUTICS.. ONE SUGGESTION TO FOCUS ON TISSUE CRIPS IN IND-ENABLING STUDIES TO DEMONSTRATE POSITIVE AND NEGATIVE, WHEN TISSUE CHIPS CAN DETECT TOXICITY THAT MOUSE MODELS DON'T HAVE, AND THAT VICE VERSA, MOUSE MODELS MAY NOT NECESSARILY REPLICATE IN HUMAN SETTINGS AND HISTORICALLY IF WE HAVE EXAMPLES OF THAT TOE REPLICATE USING TISSUE CHIPS IS ONE ASPECT. A RELATED ASPECT WHETHER OR NOT THE FDA HAS AN OPINION ABOUT THE USE OF THE TISSUE CHIPS AS PART OF IND PACKAGES, USEFUL TO COLLABORATE WITH THE FDA AND IF THEY BELIEVE THESE TISSUE CHIPS ADD VALUE TO IND SUBMISSIONS THAT PERHAPS THEY CAN PUT THAT AS PART OF THEIR GUIDANCE BECAUSE THAT WOULD DRAMATICALLY INCREASE THE USE OF TISSUE CHIPS AND I THINK IT'S A TECHNOLOGY THAT DESERVES BROADER AVALANCHE INDICATION, AND DEMONSTRATING WHERE THEY ADD VALUE AND GETTING ON BOARD WOULD BE CRITICAL. >> THANK YOU. HERE AT NCATS, WE'VE HAD PRODUCTIVE INTERACTIONS WITH THE FDA, AND IN FACT IN A PREVIOUS COUNCIL PUT FORTH A CONCEPT ACTUALLY TWO CONCEPTS THAT IS NOW ONE IS PUBLISHED, AND THE OTHER IS ABOUT TO BE PUBLISHED, SO THE FIRST ONE THAT'S PUBLISHED IS IN SOME WAYS SPECIFIC APPLICATION OF TISSUE CHIPS, FOR EXAMPLE IN TERMS OF DRUG DEVELOPMENT, BUT IN THIS CASE REPLACING AN ANIMAL MODEL, MILLIONS OF MOUSE MODELS OR MICE BEING USED FOR POTENCY ASSAY FOR BOTULISM TOXIN. WE HAVE A COLLABORATION IN TERMS OF DEVELOPING NEUROMUSCULAR JUNCTION AND CHIP TO REPLACE THE MOUTH LETHALITY LD-50 ASSAY IN USE FOR CURRENTLY FOR BOTULINUM TOXIN POTENCY. THE SECOND INITIATIVE, ALSO ALREADY CLEARED BY COUNCIL, ESTABLISHMENT OF TRANSLATIONAL CENTERS, A PARTNERSHIP BETWEEN NCATS AND FDA. WE HAVE A LETTER OF AGREEMENT FACILITATED BY OFFICE OF STRATEGIC ALLIANCE, AND THIS TRANSLATIONAL CENTER WOULD BE TO TAKE WELL ESTABLISHED TISSUE CHIP PLATFORMS THAT HAVE WELL VALIDATED DATASETS THAT IS NOW READY FOR WHAT WE CALL FIT FOR PURPOSE FOR INDUSTRY USE AS WELL AS SPECIFIC CONTEXT OF USE SATISFIED REGULATORY APPROVAL AS DRUG DEVELOPMENT TOOL AND THAT CAN BE USED AS STAND-ALONE DATASET FOR IND SUBMISSION. SO THE FDA HAS ACTUALLY STOOD UP A PROGRAM CALLED I-STAND PILOT PROGRAM WHERE THEY ARE TAKING IN VITRO PURELY IN VITRO DATA SUCH AS FROM TISSUE CHIPS, STAND-ALONE DATASET FOR AN IND APPROVAL. SO WE DO HAVE SOME PRODUCTIVE INTERACTIONS ALREADY GOING ON WITH THE FDA AND THEN IN TERMS OF THE STUDIES DONE, THERE'S BEEN EXTENSIVE STUDIES DONE WITH TISSUE CHIPS, ESPECIALLY ON LIVER ON A CHIP. HEPATOCYTES ON A CHIP. WHERE THE FIRST SITE, FIRST LINE OF TOXICITY HAPPENS IN THE LIVER SO WE WORK WITH PHARMA IN TERMS OF PROVIDING US WITH REFERENCE SET OF COMPOUNDS, WHAT HAVE BEEN COMPOUNDS THAT HAVE BEEN APPROVED FOR USE IN HUMANS THROUGH EXTENSIVE PRE-CLINICAL STUDIES INCLUDING IN VIVO STUDIES BUT HAVE SUBSEQUENTLY FAILED IN HUMAN STUDIES. SO A GREAT EXAMPLE ARE ANTI-VIRAL AGENTS USED TO BE DEVELOPED FOR HEPATITIS B HAVE BEEN APPROVED BECAUSE OF DATA COMING OUT OF ANIMALS SUBSEQUENTLY LED TO HUMAN DEATH. AND IT'S SHOWN THE HUMAN HEPATOCYTES ON A CHIP COULD HAVE PREDICTED THAT TOXICITY THAT NEITHER RAT OR DOG HEPATOCYTE ON CHIP OR EVEN RAT AND DOG ANIMALS COULD HAVE PREDICTED, LINES UP WITH WHAT YOU'RE HEARING THAT THIS SET OF TOOLS AND I THINK IT'S NO LONGER ANECDOTAL, THERE'S SEVERAL DOZEN PUBLICATIONS WHERE PHARMA AND FDA ARE USING THAT AND PUBLISHING AS WELL AS TISSUE CHIP DEVELOPERS INDICATING PREDICTABILITY IN TERMS OF SPECIFICITY AN SENSITIVITY OF USING THESE CHIPS THAT HAS INCREASED PREDICTION VALUE MORE THAN THE ANIMAL MODELS THEMSELVES. >> CAN I ASK A FOLLOW-UP QUESTION? >> SURE. >> ABOUT THE POSSIBILITY OF USE BE TISSUE CHIPS FOR LOOKING AT THE TOXICITY AND OTHER SIDE EFFECTS WITH GENE THERAPIES SPECIFICALLY? IT SEEMS THAT'S A REALLY BIG AREA OF APPLICATION AND CONTROVERSY AND WHERE YOU'RE TALKING ABOUT REAL BENEFITS TO PATIENTS IF YOU CAN DO THAT. >> CORRECT, YES. TRANSLATIONAL CENTERS THAT WE'RE STANDING UP THAT'S WHY IT TOOK A WHILE FOR LETTER OF AGREEMENT TO BE SIGNED WITH THE FDA BECAUSE WE HAVE TO INVOLVE NOT JUST CDER, THE DRUG PART OF FDA BUT ALSO CBER, AND OTHER DIVISIONS, CDRH, SPECIFICALLY BECAUSE WE ALSO HAVE SEEN EXPRESSED INTEREST IN USING TISSUE CHIPS TO IDENTIFY TOXICITIES FROM BIOLOGICS, ESPECIALLY FOR GENE EDITING OR SOMATIC CELL GENE EDITING WHERE HUMAN SEQUENCES ARE REQUIRED, THAT NO ANIMAL MODEL WOULD BE ABLE TO ADDRESS SOME OF THOSE TOXICITIES. >> THANK YOU. >> RAJESH? >> I THINK DAN -- I WAS GOING TO MEN THINGS DAN SAID, IN THE IND SPACE DAY IN AND DAY OUT, FROM A COMPANY PERSPECTIVE THE FUNDAMENTAL PIECE, UNTIL THE DAY CLEAR GUIDANCE IS ISSUED BY THE FDA THAT THEY WILL ACCEPT THIS AS PART OF THE STANDARD PACKAGE IN LIEU OF ANIMAL DATA, ALL COMPANIES, YOU KNOW, WHO INVESTED MILLIONS BEFORE THAT END UP ESSENTIALLY DOING THOSE DATA EVEN DUPLICATIVELY, TO SUBMIT THAT. AND SO I THINK IT'S SOMETHING THAT'S GOING TO TAKE TIME TO FEEL COMFORTABLE THAT THESE MODELS WILL SUPPLANT THINGS WE'VE BEEN USED TO SEEING AS PART OF DATA PACKAGES, IND DATA PACKAGES FOR DECADES. TWO SIDES OF THE COIN, ONE WHEREAS DAN POINTED OUT CAN PICK UP TOXICITIES THAT MIGHT BE MISSED BY THE ANIMAL MODELS, BUT REVERSE WHERE THERE MAY BE THINGS TOXIC IN THE ANIMAL THAT DON'T END UP BEING TOXIC IN THE HUMAN IS HARDER TO WORRY ABOUT. THOSE CHEMICALS IF YOU SHOW THEM TO BE NOT TOXIC I WOULD BE WILLING TO PUT IT IN HUMANS BECAUSE OF THE DO NO HARM PRINCIPLE. I TALK ABOUT THE FACT THAT THERE MAY BE MANY COMPOUNDS WE THROW AWAY BECAUSE THEY ARE TOXIC IN ANIMALS BUT IN FACT THEY AREN'T TOXIC TO THE SPECIES THAT MATTER, WHICH IS HUMANS, BUT WE DON'T SEE THEM. >> RIGHT, YEAH. THAT'S A GOOD POINT. I'M GLAD YOU BROUGHT IT UP. THE EARLY USERS OF TISSUE CHIPS IN TERMS OF INDUSTRY WERE LOOKING AT THAT SPACE PRECISELY WHERE YOU IDENTIFIED AND PUT YOUR FINGER ON, IN TERMS OF INTERNAL DECISION MAKING HOW DO YOU MOVE A DRUG FORWARD WHEN THE MAMMALIAN SPECIES RODENT AND NON-RODENT ONE SHOWS INCONGRUENCY IN TERMS OF TOXICITY IN ONE BUT NOT THE OTHER, DO YOU TAKE THAT OFF THE SHELF AND MOVE IT FORWARD? THEY HAVE USED TISSUE CHIPS TO MOTIVATE THEM TO PURSUE A PARTICULAR CANDIDATE THAT MAY HAVE BEEN PUT ON THE SHELF BECAUSE OF SOME ANIMAL TOXICITY BUT SHOWED NO TOXICITY IN HUMANS, MOTIVATED TO MOVE THAT CANDIDATE FORWARD AND WILL DEVELOP ADDITIONAL PRE-CLINICAL DATA TO BRING FORTH WITH THE FDA BUT AT LEAST IT'S NO LONGER IN THE DEAD ZONE OR IN THE ZOMBIE ZONE IN TERMS OF WHERE THOSE DRUGS STAND. DR. GRIMES OR DR. FERRER WANT TO COMMENT? I SEE ANOTHER HAND. >> A COMMENT, I PUT A PAPER IN THE CHAT WHICH SHOWS THE POWER OF THE APPROACH WHERE SEQUENTIAL KIDNEY AND LIVER CHIP WAS CRITICAL TO IDENTIFY THE PART OF BIOLOGY OF COMPOUND OUT OF THE ACIDS FOR TUBULAR CELL TOXICITY AND I'M INVOLVED BETWEEN FDA, CPAS AND THE ACADEMIC COMMUNITY TO DEVELOP SYSTEMS WITH KIDNEY TOXICITY AND KIDNEY ORGANOID BLOOD FORMS KEY MECHANISMS CONSIDERED AND SO I THINK THERE ARE MANY APPLICATIONS WHY THIS IS THE RIGHT TIME TO ALLOW COMPANIES TO DEVELOP COMMERCIALLY SCALABLE SOLUTIONS FOR COMPANIES AND PHARMA SO THIS IS, AGAIN, DAN CONGRATULATIONS, SYSTEMATICALLY DEVELOPED THAT FIELD FORWARD AND PROVIDING KEY SEED FUNDING WHEREVER IT IS NEEDED TO ALLOW THE COMMUNITY TO BE SUCCESSFUL. >> THANK YOU. THANK YOU ALSO FOR PROVIDING THE LINK TO THAT REVIEW ARTICLE IN TERMS OF THE LIVER AND KIDNEY CROSS-TALK. >> GO AHEAD, MARK. >> I JUST WANT TO ECHO WHAT DR. KROETZLER SAID, TO GET TISSUE CHIP TECHNOLOGY TO BASIC RESEARCH AND CLINICAL RESEARCH LABS. I THINK WHAT'S MISSING IS REALLY THE BIOLOGY COMING OUT OF THESE MODELS AND DOING IT IN AN AFFORDABLE WAY AND REPRODUCIBLE WAY. SO I THINK BY MINIATURIZING AND PUTTING -- ENABLING TO PUT THESE TECHNOLOGIES IN THE HANDS OF PEOPLE, SCIENTISTS DOING BASIC RESEARCH, WE'LL KNOW MORE ABOUT THE QUESTIONS THAT DR. LO WAS ASKING, VALIDITY OF THESE MODELS, UNDERSTANDING HOW PREDICTABLE, WHAT TYPE OF CELLS WE NEED FOR THEM TO BE PREDICTABLE AND THIS CONCEPT WOULD ALLOW US TO GET THESE INTO THE PEOPLE TO GENERATE THESE DATA, NOT ONLY PHARMA BUT ACADEMIC LABS. >> THANK YOU. ANDREW, THERE'S A COMMENT IN THE CHAT, DO YOU WANT TO STATE THAT? ASKING FOR GOOD REVIEW ARTICLE I GUESS. >> I MEAN, I THINK IT WOULD BE HELPFUL TO PULL TOGETHER ALL OF THE DIFFERENT PAPERS LIKE MATTIAS IN OTHERS IN A REVIEW ARTICLE OR WEBSITE ON NCATS THAT BASICALLY DEMONSTRATES THE VALIDITY OF TISSUE CHIPS FOR POSITIVE AND NEGATIVE READOUTS WHEN IT COMES TO HUMAN TOX STUDIES, A REPOSITORY OF REFERENCES THAT WILL GROW WITH TIME AND ADD MORE WEIGHT TO THIS TECHNOLOGY. BASED UPON WHAT I'M HEARING AND WHAT I'VE READ IN THE PAST, AND OTHER PRESENTATIONS, IT SEEMS TO ME THAT FOR VIRTUALLY EVERY KIND OF DRUG DEVELOPMENT, PART OF IND PACKAGE OUGHT TO INCLUDE EXPERIMENTATION ON TISSUE CHIPS, AND I DON'T KNOW WHETHER IT'S BECAUSE TECHNOLOGY IS REALLY EXPENSIVE OR HARD TO USE, BUT REALLY SEEMS LIKE IT SHOULD BE ONE OF THE FIRST STEPS IN ADDITION AND PERHAPS INSTEAD OF ANIMAL MODELS AND BY THE WAY YOU'LL GET A LOT OF ANIMAL RIGHTS ACTIVISTS HAPPY TO LEND SUPPORT TO YOUR EFFORTS OF DOING THIS. >> WE'VE HEARD FROM THEM. THANKS YOU FOR THE SUGGESTION. WE HAVE WRITING ASSIGNMENTS BUT WE'LL CERTAINLY ALSO PUT THE NUMEROUS PUBLICATIONS ON OUR WEBSITE SO IT CAN BE QUICKLY IDENTIFIED. >> THIS IS WIDELY USED BUT DUE TO THE DELAY BETWEEN DEPLOYMENT OF THESE UNITS, UNTIL THAT INFORMATION CAN BE RELEASED, MY TEAM IS INVOLVED IN TWO PROJECTS KIDNEY ON A CHIP WAS CRITICAL MOVING DATA FORWARD BECAUSE WE SAW CLEAR DATA IN THE KIDNEY ON A CHIP WHICH STRONGLY LED TO MATCHING HUMAN TISSUE DATA, A LOT OF EVIDENCE ALREADY CIRCULATING, SOME MIGHT NOT BE IN THE PUBLIC DOMAIN, FINDING A WAY, WE HAVE USED IN SOME INSTANCES PANEL DISCUSSION WAS INDUSTRY, WITHOUT PROVIDING SPECIFICS, TO ENDORSE THE PROCESS AT SOME UPCOMING TISSUE CHIP MEETINGS, THAT MIGHT BE ONE WAY TO BUILD STRONGER SUPPORT CONSENSUS IN DIFFERENT PLAYERS IN INDUSTRY GOING FORWARD. >> ONE MORE FOLLOW-UP QUESTION, ARE THESE TISSUE CHIPS STANDARDIZED IN ANY WAY? ARE THERE CLEAR STANDARDS FOR WHAT A LIVER CHIP WOULD CONSIST OF AND PARTICULAR QUALITY OF MANUFACTURING AND SO ON BECAUSE ONE OF THE KEYS TO BEING ABLE TO GET SOMETHING USED BROADLY IN THE INDUSTRY AND IN THE FDA IS VERY, VERY CLEAR STANDARDS THAT CAN BE APPLIED ACROSS LOTS OF LABORATORIES AND USE CASES. >> NOT YET. IN THE BEGINNING WE WANTED TO ENCOURAGE CREATIVITY AND INNOVATION AND DID NOT WANT STANDARDS IN TECHNICAL SPECIFICATIONS TO COME IN BUT SINCE 2014 THIS PROGRAM STARTED IN 2012, SO 2014 WE STARTED WORKING A LOT MORE WITH PHARMA AND INDUSTRY, AND THAT HAS NOW LED TO A SERIES OF PUBLICATIONS FROM PHARMA INDICATING WHAT KIND OF STANDARDS THAT WOULD SATISFY FIT FOR PURPOSE FOR INDUSTRY USE, PUBLICATIONS THAT THEY HAVE PUT OUT, AND THEN TRANSLATIONAL CENTERS THAT WE ARE ESTABLISHING WILL ONLY TAKE THOSE PLATFORMS THAT ACTUALLY ARE STANDARDIZED AND SATISFY FIT FOR PURPOSE SO WE CAN BRING THEM FORWARD TO THE FDA AS PART OF OUR PARTNERSHIP BETWEEN FDA AND NCATS IN TERMS OF EVALUATING FDA EVALUATING THEM AND QUALIFYING THEM AS DRUG DEVELOPMENT TOOLS. >> THANK YOU. >> OKAY. THANK YOU FOR THAT GREAT DISCUSSION. THAT WAS TERRIFIC. I THINK IF THERE'S NO FURTHER DISCUSSION, ANNA, DO YOU WANT TO GET A MOTION PLEASE? >> YES, IT'S TIME TO VOTE. COULD I HAVE A MOTION TO APPROVE THE CONCEPT? >>> MOVED. >> SECOND? >> SECOND. >> ALL IN FAVOR? >> AYE. >> AYE. >> AYE. >> YES. >> ANY OPPOSED? ANY ABSTENTIONS? WITH THAT OUR MATCHs CONCEPT HAS BEEN APPROVED. >> BACK OVER TO DAN. KEEP GOING. >> THANK YOU. NEXT SLIDE PLEASE. SO THE NEXT CONCEPT WILL BE A CONTRACT USING SMALL BUSINESS SOLICITATION PROCESS, FOR SMALL MANUFACTURING SYSTEMS TO PRODUCE RESEARCH GRADE PHARMACEUTICAL INTERMEDIATES. NEXT SLIDE PLEASE. WHERE IS THIS NEED COMING FROM? THE DRUG DEVELOPMENT PIPELINE CAN BE EXTENSIVE AND COSTLY. WITH DEVELOPMENT OF PRE-CLINICAL DRUG CANDIDATES, FROM $2.6 BILLION AND LASTING FROM 10 TO 15 YEARS, BUT THIS REALLY HINGES A LOT ON THE QUALITY AND ACCESS TO CLEAR PHARMACEUTICAL INTERMEDIATES, TO WORK ON FOR SCREENINGS AND FURTHER DEVELOPMENT AS LEAD AGENTS. AND SO WHAT WE ARE PROPOSING IN THIS CONCEPT WOULD BE PRETTY MUCH AN ON-DEMAND ACCESS TO PHARMACEUTICAL INTERMEDIATES THAT WE HOPE TO SPEED UP THE DESIGN SYNTHESIS TEST CYCLE IN THE SYNTHESIS PART AS THE NEXT ANIMATION WILL SHOW. CAN YOU CLICK? YEP. THAT WOULD BE ON THE FIRST PART OR THE DESIGN SYNTHESIS PROCESS, WHICH IS LARGELY ON THE CHEMISTRY SIDE OF THINGS. NEXT SLIDE PLEASE. IN TERMS OF BRIEF BACKGROUND, AS I ALREADY MENTIONED, THE CHEMICAL SPACE AND DRUG DEVELOPMENT PROCESS REQUIRES ESSENTIALLY EASY ACCESS TO BULK PHARMACEUTICAL INTERMEDIATES MADE IN HOUSE OR CRO AND OF COURSE BECAUSE OF THE EXTENSIVE AND TIME-CONSUMING PROCESS IT'S LARGELY BEING DONE RIGHT NOW THROUGH CRO, WHICH ADDS TO THE LENGTHY PROCESS. AND SO OUR FOCUS WOULD BE ON SYNTHESIS, DIRECT CANDIDATES, TO ESSENTIALLY EMPOWER CHEMIST TO HAVE THESE TOOLS AVAILABLE AT THEIR DISPOSAL. WHAT WE'RE DOING IS LEVERAGING AUTOMATION AND SYNTHETIC CHEMISTRY, THAT IS ALREADY AROUND, ESPECIALLY IN TERMS OF SPECIALIZED PHARMACEUTICAL INTERMEDIATES AND TREATMENTS, BE ABLE TO RAPIDLY SCALE THIS UP USING IN-HOUSE DEVICE. NCATS IS PROPOSING THIS CONCEPT TO DEVELOP TOOLS TO INCREASE SYNTHETIC CHEMISTRY THROUGHPUT AND REDUCE TIME FOR PRE-CLINICAL CANDIDATES. THE INDUSTRY ITSELF IS ABOUT $40 BILLION A YEAR, IN TERMS OF THE INTERMEDIATES AND SO WHAT WE'RE DOING IS LOOKING FOR A WAY TO INCREASE ACCESS TO THOSE INTERMEDIATES. NEXT SLIDE PLEASE. OBJECTIVES TO DEVELOP TOOLS FOR PHARMACEUTICAL INTERMEDIATES, THE NEXT GENERATION OF PEPTIDE SYNTHESIZERS, OF COURSE THEY ARE PRETTY MUCH LIMITED TO COUPLING SO WE WANT A MORE SOPHISTICATED AND CERTAINLY MUCH ADVANCED WAY OF DOING CHEMISTRY THAT YOU CAN DO CARBONYL COUPLING AND OTHER CHEMISTRIES, NOT BEING ABLE TO BE PER FORMULARY OF -- PERFORMED RIGHT NOW. KEY AREAS TO EMPHASIZE UTILIZATION OF CURRENT AUTOMATION TECHNOLOGY, IN TERMS OF SYNTHETIC CHEMISTRY ADAPTABLE TO METHODOLOGIES, DEVELOP TECHNOLOGY AMENABLE TO REALTIME DATA ACQUISITION AND MONITORING. NEXT SLIDE. THE CURRENT ACTIVITIES WE HAVE RELATED TO THIS PROPOSAL IS ALREADY INCLUDING ASPIRE PROGRAM, RIGHT NOW AN ONGOING PROGRAM A COLLABORATION WITHIN NCATS BETWEEN EXTRAMURAL SCIENTISTS AND ALSO INTRAMURAL DPI SCIENTISTS. AND WE ALSO HAVE AN NCATS DARPA COLLABORATION FOR FLEXIBLE MANUFACTURING OF FINE CHEMICAL REAGENTS, BUT THAT'S JUST RELATED PRIMARILY TO THE END PRODUCT. THIS CONCEPT WILL ADD ESSENTIALLY SOME VALUE TO THESE EFFORTS BY PROVIDING ADDITIONAL SUPPORT TO DEVELOP NON-GMP REAGENTS FOR LABORATORY USE RECOGNIZING CHEMISTRY WILL IMPROVE RATE OF DEVELOPMENT OF CHEMICAL CANDIDATES, PRE-CLINICAL CANDIDATES, AND ALSO IMPROVING ACCESS TO PHARMACEUTICAL INTERMEDIATES WILL INCREASE RATE OF DRUG CANDIDATE DEVELOPMENT AND BIOLOGICAL DATA GENERATION FOR STORING CHEMICAL SPACE. SUCCESS WILL BE CREATION OF AUTOMATED SYNTHETIC CHEMISTRY DEVICE FOR PREPARATION OF PHARMACEUTICAL INTERMEDIATES. SUCCESS RATE IS AROUND 50%, TALKING YOU TO EXPERTS IF WE ARE ABLE TO COME UP WITH THIS DEVICE IT COULD IMPROVE ACCESS AND SUCCESS TO DEVELOPING CLINICAL CANDIDATES BY AS MUCH AS 8 5 TO 90%. SO NEXT SLIDE PLEASE. SO THIS IS A CONTRACT SOLICITATION. THERE ARE A FEW KEY QUESTIONS THAT WE NEED TO PUT FORTH BEFORE COUNCIL IN TERMS OF WHAT SATISFIES A CONTRACT SOLICITATION SO FIRST SCIENTIFIC TECHNICAL AND PROGRAMMATIC SIGNIFICANCE, SO WE THINK THE DEVELOPMENT, SIGNIFICANCE WOULD BE IN DEVELOPMENT TOOLS, AUXILIARY TO WORK FLOW, LATE-STAGE CHEMICAL INTERMEDIATES, EXPANSION OF CHEMICAL SPACE, DATA COLLECTION FROM THIS TECHNOLOGY TO ALLOW FOR STANDARDIZED METHODS AND HAS HIGH SIGNIFICANCE AND RELEVANCE TO THE ASPIRE PROGRAM RIGHT NOW IN TERMS OF DEVELOPING AUTOMATED TOOLS TO EXPAND DRUGGABLE CHEMICAL SPACE. IN TERMS OF AVAILABILITY OF TECHNOLOGY AND OTHER RESOURCES, CERTAINLY THERE ARE MAJOR ADVANCES MADE IN THE FIELD IN TERMS OF FLOW CHEMISTRY AND AUTOMATED BATCH PRODUCTION AND WE WANT TO HARNESS THAT IN TERMS OF THIS PROGRAM, AND INTEGRATE THEM AND THEN ALSO BE ABLE TO FURTHER DEVELOP DATA COLLECTION. WE ARE ASKED TO ADDRESS EXTENTS TO WHICH IDENTIFIED PRACTICAL AND SCIENTIFIC OR CLINICAL USE IS AND SO WE THINK CERTAINLY AVAILABILITY OF SUCH A PLATFORM WOULD LEAD TO WIDESPREAD ADOPTION, WILL LEAD TO RAPID DEVELOPMENT OF PRE-CLINICAL DRUG CANDIDATES AND THEN THE LAST SLIDE SHOULD BE OUR USUAL SUMMARY, IN TERMS OF REITERATING THIS CONCEPT INCREASED ACCESS TO PRE-CLINICAL CANDIDATES BY SHORTENING DESIGN SYNTHESIS TEST CYCLE IN DRUG CHEMISTRY, ON THE EARLY DRUG DISCOVERY SIDE OF THINGS AND INTRODUCTION OF LABORATORY TOOLS TO FOCUS ON EXPLORATION OF CHEMICAL AND BIOLOGICAL SPACE AND GREATLY IMPACT RESEARCH AND DRUG DISCOVERY BY INCREASING THROUGHPUT OF CHEMISTRY TO MORE CLOSELY MATCH HIGH-THROUGHPUT BIOLOGICAL AND ANALYTICAL METHODS. AND THEN THE NEXT SLIDE, LAST SLIDE, SHOULD BE OUR USUAL QUESTIONS FOR COUNCIL, IN TERMS OF WHAT CAN BE DONE TO IMPROVE THIS INITIATIVE AND WHAT ARE THE KEY POINTS THAT WE NEED TO PUT INTO CONSIDERATION. AND, AGAIN, WHO ARE THE POTENTIAL PARTNERS THAT MAY BE INTERESTED AND SO AT THIS POINT I'D LIKE ALSO TO INVITE OUR STAFF PANELISTS THAT WILL BE DR. ALEX GODFREY WHO HEADS THE ASPIRE PROGRAM IN THE INTRAMURAL DIVISION FOR PRE-CLINICAL INNOVATION, AND THEN OSI STAFF WHO ARE RESIDENT CHEMISTS AT OSI, DR. SEAN GARDNER AND ALSO DR. CHARISSE JOHNSON. >> OKAY. THANK YOU, DAN. I WILL TURN IT OVER TOE -- TO TED FIRST. THE FIRST DISCUSSANT. >> SURE. THANKS FOR THE PRESENTATION. THE IDEA IS WONDERFUL. BUT, MAN, THERE'S SO MANY DIFFERENT TYPES OF SYNTHETIC STEPS. PEPTIDE SYNTHESIS IS STRAIGHTFORWARD BECAUSE YOU'RE NOT CHANGING THE CHEMISTRY MUCH. WHAT DO YOU ENVISION, LIKE HOW MANY TYPES OF CHEMICAL REACTIONS ARE YOU THINKING THIS THING COULD DO? >> SEAN CAN ANSWER THAT QUESTION. >> YOU'RE MUTED. >> IN TERMS OF THE NUMBER OF CHEMICAL REACTIONS, THOUGHT OF WITHIN THE DEVELOPMENT OF THE SPECIFIC TECHNOLOGY THAT THE SYSTEM WOULD USE, A LOT OF CURRENT RESEARCH GOING ON IN THE FIELD OF FLOW CHEMISTRY THAT KEEPS INTRODUCE NEW REACTIONS TO SMALLER SYSTEMS. THE NUMBER OF REACTIONS TYPICAL SYSTEMS CAN DO GROWS BY THE DAY, THERE'S ALSO A NUMBER OF OTHER DIFFERENT TECHNOLOGIES IN TERMS OF SOLID SUPPORT, CATALYSTS, AND THINGS OF THAT NATURE THAT ALSO, AGAIN, RAPIDLY ARE INCREASING THE NUMBER OF AVAILABLE TRANSFORMATIONS THAT AUTOMATED SYSTEMS CAN DO. SO I HOPE THAT ANSWERS YOUR QUESTION. >> AS I MAKE MY DRUGS, THERE ARE MANY DIFFERENT REACTIONS THAT POP UP. AND SO YOU'RE HOPING THAT THERE BE LIKE A MENU THAT YOU WOULD HAVE ALL THESE AVAILABLE REACTIONS YOU COULD DO, AND SO THEN YOU WOULD TYPE IN THE MENU, WE'RE GOING TO USE THIS SUZUKI COUPLING OR SOMETHING LIKE THAT, PLUG THAT IN, INTO THE AUTOMATION, OFF IT GOES. IS THAT WHAT YOU'RE ENVISIONS? >> YES. >> A MENU OF DIFFERENT REACTIONS? >> YES, THERE WOULD BE A SET OF, AGAIN, I LIKE THE COMPARISON TO A MENU, OF REACTIONS THAT ONE CAN DO WITH THE SYSTEM AND WITH THE HOPE THAT IT WOULD CONTINUE TO GROW AS THE SYSTEMS PROLIFERATE, SO AS MORE PEOPLE BEGIN TO USE AUTOMATED SYSTEMS FOR SYNTHESIS AS THEY ALREADY DO FOR THINGS LIKE PURIFICATION VIA CHROMATOGRAPHY AND SOLID SUPPORT CATCH AND RELEASE PURIFICATION METHODS THERE WILL BE AN INCREASING MARKET FOR DEVELOPMENT OF TRANSFORMATIONS THAT COULD BE DONE ON THESE SYSTEMS. RIGHT OFF THE BAT IT'S NOT GOING TO BE SOMETHING THAT'S GOING TO BE ALL ENCOMPASSING BUT, YEAH, I DEFINITELY SEE THERE COULD BE GROWTH WITH PLATFORMS LIKE THIS. >> AND SO THEN HOW ABOUT THE OTHER CHALLENGE OF SYNTHESIS IS THE PURIFICATION AFTER EACH STEP OF MAKING -- RARE RARELY DO YOU GET 100% CONVERSION. IS THERE A PURIFICATION COMPONENT TO THIS INSTRUMENT? >> THIS ALSO GOES INTO THE DEVELOPMENT OF CHEMISTRIES THAT WILL BE ABLE TO BE USED WITH IT. SO THERE ARE REACTIONS THAT CAN BE USED THAT -- WHAT'S THE WORD I'M LOOKING FOR? IN LINE RECRYSTALLIZATION FOR SOLID INTERMEDIATES IS SOMETHING THAT COULD REALLY HELP GET RID OF IMPURITIES AND WHAT NOT. AND IT'S REALLY GOING TO ALWAYS BE A CASE-BY-CASE BASES ON WHAT MOLECULE YOU'RE WORKING WITH. BUT AS MENTIONED THERE ARE A VARIETY OF ALREADY AUTOMATED PURIFICATION STRATEGIES THAT ARE -- WE WOULD HOPE WOULD BE COUPLED INTO A SYSTEM LIKE THIS SUCH AS AUTOMATED CHROMATOGRAPHY, CATCH AND RELEASE RESINS, SOLID SUPPORTED CATALYSTS WHICH HOLD METAL IN PLACE SO IT DOESN'T GO INTO THE NEXT STEP. AND TELESCOPING REACTIONS, YOU CAN DO MULTIPLE TRANSFORMATIONS WITHIN ONE REACTION AND SOLUTION. >> IT'S AMAZING, YOUR VISION IS INCREDIBLE. THERE'S SO MANY THINGS THAT GO INTO PLAY WITH IT, WE TRY AND MAKE OUR DRUGS, OH MY GOD, MAKING ONE RIGHT NOW, IT'S ONLY THREE STEPS, STRAIGHTFORWARD, BUT ALL THESE THINGS CAN SCREW UP ALONG THE WAY. I'M IMPRESSED YOU'RE GOING TO TRY AND GO FOR THIS. >> THAT'S PART OF THE REASON WE WANTED TO BE A CONTRACT, TO SPECIFY THE THINGS THAT YOU ARE TALKING ABOUT IN TERMS OF SYNTHESIS, KIND OF CHEMICAL REACTIONS, FINAL STEP OF PURIFICATION PROCESS IN TERMS OF WHAT THAT SHOULD LOOK LIKE. >> REALLY LENDS ITSELF TO A CONTRACT MECHANISM. >> IT'S AN AUDACIOUS GOAL BUT WE'LL SEE. >> THAT'S WHAT WE DO AT NCATS. >> AN OPPORTUNITY, IF YOU LOOK AT THE -- >> WE DON'T SEE YOU, ALEX. >> I SEE YOU. GO AHEAD, ALEX. >> YEAH, SO THE HISTORY OF DEVELOPMENT OF AUTOMATED PLATFORMS GOES BACK TO -- YOU MENTION THE PROTEIN PEPTIDE SYNTHESIS, A NOBEL PRIZE FOR THAT, SINCE THEN WE'VE GOTTEN OLIGONUCLEOTIDE SYNTHESIZERS, POLYSACCHARIDE SYNTHESIZERS AND SO FORTH. WE KEEP BUILDING OUR ARMAMENTARIUM, SPECIALIZED SYNTHESIZERS, RIGHT? BUT ONE OF THE BIGGEST CHALLENGES, AND THERE'S GREAT POTENTIAL HERE, NO PUN INTENDED, THE REDOX CHEMISTRY. FOR INSTANCE THESE CARBON-CARBON COUPLING TECHNOLOGIES AROUND THE SUZUKI COUPLING REACTION, BUT THOSE RAW MATERIALS HAVE TO COME FROM SOMEONE, THE CHICKEN-AND-EGG PROBLEM, RIGHT? ONE OF THE BIGGEST KIND OF HURDLES TO CROSS IS BEING ABLE TO DO REDOX CHEMISTRY, OXIDATION REDUCTION IS A DIFFICULT PART TO GENERALIZE, BUT THERE'S BEEN A BOON IN RECENT YEARS, ELECTRO CHEMICAL KA -- CATALYSIS IN GENERAL, TO HELP ADDRESS THIS GAP THAT CURRENTLY EXISTS WHICH IS AROUND REDOX CHEMISTRIES. IF WE CAN COVER THAT NICHE WE GOT A HUGE BOLUS OF OPPORTUNITY COVERED THAT DRIVES TOWARD THIS AUTOMATION NICHE. >> NO, IT'S A WONDERFUL IDEA. IT DEPENDS HOW WE COUPLE THE TECHNOLOGIES BUT IT'S POSSIBLE. THANKS. >> RAJ? >> HAVE BOTH DISCUSSANTS GONE? >> NO. >> I CAN WAIT. >> NEXT UP IS ANNIE KENNEDY. >> I'LL BE BRIEF. IT DOES ALIGN WITH THE EARLIER COMMENT, WHAT RESONATES WITH ME IS WHAT DR. DR. KA KURILLA MENTIONED MORNING TO STREAMLINE EFFORTS AND OUR AIM TO DOING THAT. I HAVE A QUESTION AROUND STRENGTHENING EVERY TIME A NEW INNOVATION OR TECHNOLOGY IS DEVELOPED, IT SEEMS A NEW WORKFORCE NEEDS TO ACCOMPANY OR SUPPORT THAT AND I'M WONDERING WHERE THAT FALLS WITHIN -- DOES THAT FALL WITHIN THE NCATS MISSION, DOES THAT BUBBLE UP ALONGSIDE NATURALLY THIS IS SOMETHING THAT FOLLOWS OUTSIDE OF MY DAILY JOB BUT IN THE TIMES I'VE SPENT TIME IN LABS THERE'S AN ENTIRE WORKFORCE SURROUNDING ANY PIECE OF EQUIPMENT AND ANY TECHNOLOGY, SO I'M WONDERING IS THERE THOUGHT INTO THE WORK FORCE ALONGSIDE AND HOW THAT HAPPENS AND GETS BUILT INTO THE OTHER THAT NCATS FUNDS? >> THANK YOU, ANNIE, FOR THAT QUESTION. CERTAINLY THE END GOAL, THAT'S WHY WE'RE PROPOSING THIS, SMALL BUSINESS ACTIVITY, IS THAT IT WOULD BE COMMERCIAL COMPANIES COMING UP WITH THIS INSTRUMENTATION, PROVIDING AS TYPICAL SERVICE TO ANY NEW PLATFORM TRAINING TO TECHNICIANS AND PERHAPS POSTDOCS OR GRADUATE STUDENTS. SO I DON'T -- THE REQUIRED PART OF THE CHALLENGE IS HOW USER FRIENDLY ARE GOING TO BE THE PLATFORMS. AND THAT'S ONE OF THE CENTRAL CHALLENGES IN TERMS OF COMMERCIAL VIABILITY IS THE USABILITY OF THE DEVICE SO CERTAINLY THAT'S SOMETHING WE WILL BUILD INTO THE CONTRACT SOLICITATION TO MAKE SURE IT'S NOT -- YOU DON'T NEED A Ph.D. DEGREE TO BE ABLE TO USE ONE OF THOSE DEVICES. >> I DECIDE WHAT SUCCESS LOOKS LIKE, DELIVERABLES, AROUND AN AUTOMATED SYNTHETIC CHEMISTRY DEVICE BUT FURTHER DEVELOPMENT FOR DATA COLLECTION AND STANDARDIZATION IS A REALLY IMPORTANT DELIVERABLE. SO UNDERSCORING THAT WHEN YOU AWARD AND RESPONSIBILITIES. >> RIGHT. WHOLEHEARTEDLY AGREE WITH THAT. SEAN, YOU HAVE SOMETHING TO ADD? >> I ALSO AGREE WITH THAT AS WELL. A LOT OF WHAT IS INVOLVED WITH THE UPTAKE OF TECHNOLOGY, ESPECIALLY I'M A SYNTHETIC CHEMIST BY TRAINING, LABORATORY CONSUMABLES, HOW AVAILABLE ARE THESE THINGS NON-SPECIALIZED SOURCES, VIALS, SYRINGES, TUBING, HAVING THEM BE DESIGNED AROUND HAVING THIS TECHNOLOGY DESIGNED AROUND SPECIALIZED PIECES OF EQUIPMENT THAT WILL KEEP A RESEARCH GROUP AND EXPENSIVE ECOSYSTEM SO TO SPEAK IS NOT WHAT WE'RE ENVISIONING WITH THIS CONCEPT. >> THANK YOU. RAJESH? >> MY COMMENT IS, YOU KNOW, PERHAPS SLIGHTLY TONGUE IN CHEEK BUT STILL IMPORTANT TO CONSIDER THAT IF YOU ARE SUCCESSFUL, THE VERY PEOPLE YOU'RE THINKING WILL ADOPT THIS ARE THE VERY PEOPLE WHO WILL NOT WANT TO ADOPT IT. BECAUSE IT ACTUALLY WILL DRAMATICALLY REDUCE THEIR WORK FORCE BECAUSE YOU'RE REPLACING THEM. OF COURSE WE SHOULD DO THAT, BUT I THINK YOU'RE MAKING AN ASSUMPTION THAT EVERY MEDICINE CHEMISTRY DEPARTMENT WILL IMMEDIATELY WANT TO BUY YOUR ROBOT AND PUT IT ON THE BENCH BUT THEY DO AND HAVE TO FIRE TEN PEOPLE SO THEY HAVE TO THINK ABOUT THAT, SO TO SPEAK. KEEP THAT IN MIND. >> YEAH. THANK YOU. THIS ACTIVITY IS LARGELY DONE FOR CROs, OUR GOAL IS TO MAKE THIS AN INHOUSE THING. >> THEY MIGHT CLAIM BLOODY MURDER. >> WE'LL FIND OTHER USES LIKE INCORPORATE BE TISSUE CHIPS INTO THE CRO SERVICES. >> THERE YOU GO. ALEX DID YOU HAVE A COMMENT? YOU'RE ON MUTE. >> I HEARD THIS ARGUMENT QUITE A BIT OVER THE YEARS ABOUT THE ROBOTS COMING TO TAKE OUR JOBS. I THINK THE KEY THING IS TO DEVELOP A ELEVATOR SPEECH IT THAT TALKS ABOUT AUGMENTATION STRATEGY. THIS IS NOT REPLACEMENT, IT'S AUGMENTATION. YOU'VE GOT THE PEOPLE YOU GOT, YOU WANT TO GET THE MOST OUT OF THEIR PRODUCTIVITY, RIGHT? I THINK IT'S REALLY IMPORTANT THAT AS WE PITCH THIS, WE'RE PITCHING THIS AS AUGMENTATION, NOT JOB REPLACEMENT STRATEGY. >> GREAT. >> THAT'S WHY I SAID IT TONGUE IN CHEEK, A MATTER OF HOW YOU MARKET IT. ALSO THE OTHER PIECE AND ON A MORE SERIOUS NOTE YOU NEED TO -- WHEN A TECHNOLOGY SPEAKS FOR ITSELF YOU DON'T HAVE TO REALLY WORRY ABOUT MAKING THAT ARGUMENT. IT WILL GET ADOPTED. SO I THINK THE -- IF YOU CAN GET TO WHERE IT'S A NO-BRAINER THAT THE GROUP ITSELF CAN BE MORE SUCCESSFUL IN MAKING THE COMPOUNDS THAT ARE EXPECTED BY THE POWERS THAT BE, THEN THEY WILL CLAMOR FOR THAT THEMSELVES. >> WE HAVE A COMMENT FROM LILI. CAN YOU UNMUTE AND GO AHEAD. >> JUST TO SAY THESE ARE THE THINGS WE WOULD EXPECT A VENDOR TO BE VERY CLEAR IN COMMERCIAL DEVELOPMENT PLAN WHEN THEY GO INTO THE PHASE 2 PORTION OF THE CONTRACT. THEY ARE GOING TO HAVE TO LAY OUT MARKET SIZE AND HOW THEY INTEND TO CREATE ENTRY POINTS AND THINGS LIKE THAT. SO WE'LL DEFINITELY CAPTURE THAT AS PART OF THE REVIEW. >> OKAY. AND THEN -- >> IF YOU'RE GOING TO DO THAT ONE THING YOU MIGHT WANT TO THINK ABOUT HAVING THEM DO AS A COMPANY, WHOEVER WINS THESE AWARDS AND NEEDS TO PRESENT THAT, OFTEN WHAT KILLS THESE THINGS IS ASSUMPTIONS ABOUT WHAT THE END USER WANTS OR DOESN'T WANT AND SO TO ENSURE THAT YOU'RE DOING WHAT TENDS TO BE CALLED USER SURVEYS YOU ENSURE THAT THE COMMERCIAL PARTNER UNDERSTANDS THEIR CUSTOMERS' NEEDS IN A CAREFUL WAY AS THEY ARE THINKING ABOUT THE COMMERCIALIZATION PIECE AND SMALLER COMPANIES DON'T TEND TO DO A GOOD JOB. THEY JUST ASSUME THEY HAVE DEFINED THE NEED AND ONCE THEY MAKE THE THING IT WILL AUTOMATIC LIP SELL OFF THE SHELVES AND THEN THAT DOESN'T HAPPEN AND THEN, YOU KNOW, YOU HAVE A POOR COMMERCIAL -- IF YOU DON'T HAVE A GOOD COMMERCIAL LAUNCH IT'S MUCH MORE CHALLENGING FOR SECOND GEN AND OTHERS TO IMPROVE. >> GREAT COMMENT. I WANTED TO ADD THAT ANDREW LO WAS A DISCUSSAND AND LEFT SOME NOTES IN THE CHAT I WANTED TO READ. APOLOGIES, HE HAD TO A HARD STOP AT FIVE, ANOTHER TERRIFIC PROJECT REDUCING VARIABILITY, INCREASING QUALITIES OF ACADEMIC WORK INVOLVING SMALL MOLECULE DRUG CANDIDATES. I WOULD IMAGINE THERE WOULD BE MULTIPLE INDUSTRIAL PARTNERS INCLUDING A.I. BASED COMPANIES TAPPED TO CONTRIBUTE RESOURCES TO THIS INITIATIVE AND HE OFFERED TO MAKE INTRODUCTION AND CONGRATULATE THE TEAM ON GREAT PROCESS AND INSPIRATIONAL DAY AND DID ADD, IF THERE WAS ANY DOUBT WHATSOEVER THAT HE DOES SUPPORT THIS CONCEPT WHOLEHEARTEDLY, WITH THAT I WANT TO -- WE'VE EXHAUSTED OUR DISCUSSION AND CAN TURN TO ANNA FOR CAPTURING THE MOTION. >> THIS IS OUR FINAL CONCEPT FOR THE DAY. THERE IS NO FURTHER DISCUSSION AS I CAN TELL. LET'S GO AHEAD AND MAY I HAVE A MOTION TO APPROVE THE CONCEPT? >> SO MOVED. >> SECOND? >> SECOND. >> SECOND. >> ALL IN FAVOR? >> AYE. >> AYE. >> AYE. >> ANY OPPOSED? ANY ABSTENTIONS? WITH THAT OUR LAST CONCEPT OF THE DAY IS SAY -- IS APPROVED. THANK YOU VERY MUCH. >> YES, THANK YOU. >> HEAR, HEAR. I WANT TO THANK YOU FOR THE GREAT DISCUSSIONS FOR ALL OF THE CONCEPTS AND PRESENTATIONS, AS ALWAYS THIS IS SUCH A RICH TIME TO HAVE THESE CONVERSATIONS AND ONCE AGAIN I'VE TAKEN A LOT OF NOTES AND I'M SURE THE TEAM WILL BE FOLLOWING UP ON INCORPORATING SOME OF THESE IMPORTANT INSIGHTS AS WELL. AND HOPEFULLY YOU'LL SEE THEM ON THE FLIP SIDE WITH UPDATES AS WE KEEP GOING AND YOU'LL HEAR MORE. WITH THAT, ARE THERE ANY OTHER ANNOUNCEMENTS WE NEED TO MAKE? >> THERE ARE NOT. >> OKAY. WE'RE GOOD TO GO. AGAIN, THANK YOU SO MUCH. I'M GOING TO TRANSITION AND SIGN OUT. THANK YOU, EVERYONE. WE'LL SEE YOU NEXT TIME.