>>WELCOME
TO THE OPEN SESSION OF THE
DIVISION OF MICROBIOLOGY AND
INFECTIOUS DISEASE SUBCOMMITTEE
COUNCIL. OUR AGENDA IS ON THIS
SLIDE. I'LL GIVE A BRIEF
PERSONNEL UPDATE, INTRODUCE BY
SLIDE SOME NEW STAFF. I WILL
GIVE SOME HIGHLIGHTS FROM DMID
FUNDED RESEARCH THAT'S BEEN IN
THE NEWS SINCE LAST TIME WE MET.
WE'LL HAVE A PRESENTATION BY DR.
EWE ZIKA HEWITT WHO IS DEPUTY
DIRECTOR OF PRE-CLINICAL
SERVICES BECAUSE THAT IS BUNDLE
OF OUR INITIATIVES FOR CONCEPT
CLEARANCE THIS AFTERNOON AND
THERE WERE QUESTIONS RAISED HOW
DOES THIS SYSTEM WORK AND FIT
TOGETHER SO WE THOUGHT THAT
BACKGROUND WOULD BE USEFUL TO
FRAME THE DISCUSSI DISCUSSION. L
YEAR 25 CONCEPTS CLEARANCE. SO
THEN WE WILL HAVE THE FOUR
INITIATIVES, DMID INITIATIVES
PRESENTED T THAT ARE LISTED ON
THIS SLIDE, FOLLOWED BY A
CONCEPT CLEARANCE REQUESTED FOR
THE OFFICE OF DATA SCIENCE AND
EMERGING TECHNOLOGIES THAT WILL
BE PRESENTED BY DR. REEDE
SHABMAN AT THE END. SO THIS IS
OUR AGENDA THIS AFTERNOON. FIRST
OF ALL, IN THE OPEN SESSION
REMARKS OF THE NIAID COUNCIL
EARLIER TODAY YOU HEARD ABOUT
THE RETIREMENT OF MARK SHULBURG,
MARK WAS AN EMPLOYEE OF NIAID
FOR OVER 37 YEARS WHICH IS
REMARKABLE FOR THE INTRAMURAL
PROGRAM WHERE HE WORKED IN THE
LAB WITH DIRECTED BY BERNIE MOSS
THEN CAME TO NIAID EXTRAMURAL
DMID A FEW YEARS, PROBABLY STILL
BEEN DECADES BUT HE -- I VALUED
IN THE YEARS HE WAS VIROLOGY
BRANCH CHIEF ABOUT THREE YEARS I
VALUED HIS UNPUT AND DISCUSSIONS
I HAD WITH HIM ON SOME BIGGEST
CHALLENGES LIKE HBV CURE,
GETTING A VACCINE FOR HEPATITIS
C. DEVELOPING A VACCINE FOR ZIKA
SO WE ARE GOING TO MISS MARK BUT
WE ARE HAPPY GENE PATTERSON IS
IN PLACE AND IS GOING TO TAKE ON
THE ROLE OF ACTING VIROLOGY
BRANCH CHIEF. SO WITH HER OWN
NAME ON THE TENT IN FRONT OF HER
AT THE TABLE HERE AND LOOK
FORWARD TO WHAT GENE CONTINUES
TO DO FOR DMID AND LEADERSHIP
FOR THE UPCOMING YEARS. WE HAVE
A FEW NEW STAFF TO MENTION THAT
HAVE COME ON BOARD SINCE LAST
TIME WE MET. CHRISTIAN GONZALES
IS A PRODUCT DEVELOPMENT
SPECIALIST, PRODUCT DEVELOPMENT
PROGRAM MANAGER WHO IS MOVING
FROM ESTIB TO THE RESPIRATORY
DISEASE BRANCH. NOT REALLY NEW
BUT A TRANSITION. NEW ROLE.
ROCHELLE SMITH IS A PRESIDENTIAL
MANAGEMENT FELLOW ACCEPTING A
POSITION IN THE VIROLOGY BRANCH
WHERE SHE WILL WORK WITH THE
CREED NETWORK. SHE STILL IS A
PNF BUT SHE IS OVER THE NEXT
MONTH MOVE INTO A FULL TIME
POSITION WITH US. SHE GRADUATE
WITH A Ph.D. IN CHEMISTRY FROM
OREGON STATE UNIVERSITY AND MOST
OF HER PRESIDENTIAL MANAGEMENT
FELLOWSHIP EXPERIENCE WAS WITH
NCI. THEN THE LAST NEW MEMBER OF
OUR TEAM IS DR. WILL SEARS WHO
JOINED THE OFFICE OF CLINICAL
RESEARCH RESOURCES, LAST MONTH
AND HE COMES TO US AFTER HE
FINISHED HIS INFECTIOUS DISEASE
FELLOWSHIP AT NIAID BUT WORKING
IN THE DIVISION OF INTRAMURAL
RESEARCH. WILL IS COMBINED
PHYSICIAN, HE DID A COMBINED
MEDICINE PEDIATRIC RESIDENCY AT
INDIANA UNIVERSITY AND HIS
RESEARCH AT NIAID DURING HIS
FELLOWSHIP WAS CONDUCTED DONOR
THE LAB OF TOM (INAUDIBLE) IN
THE LAB OF PARACYTIC DISEASE. HE
WORKED IMMUNE RESPONSE WORKING
ON EOSINOPHILIC MENINGITIS AND
DIAGNOSTICS AND GENOMICS OF MANY
DIFFERENT HELMETS SO HIS FOCUS
WILL BE ON DEVELOPING SKILLS IN
CLINICAL TRIALS AND
PARACYTOLOGY. SO NOW I WILL MOVE
TO NEWS. YOU HEARD FROM DR.
AUCHINCLOSS THE NEW INSTITUTE
DIRECTOR WELCOMING SOON IS DR.
(INAUDIBLE). THOSE COMING TO
THESE MEETINGS AT LEAST A YEAR
MIGHT RECALL THAT A YEAR AGO SHE
PRESENTED BY ZOOM THOUGHTS ON UT
PRIORITIES AND SEXUALL THAT'S
THE TESTING OF THE ME
JINKCOCCAUL MEMBRANE THAT -- IN
THE BEXE ARE, ARER TRIAL AND
PROTECTED MEASURE AGAINST
GONORRHEA. SHE HAS BROAD
BACKGROUND IN NON-HIV SEXUALLY
TRANSMITTED INFECTION AND HIV.
SHE ALSO SEVERAL YEARS AGO
CONCLUDED THE VOICE TRIAL WHICH
WAS A TRIAL RECRUITING WOMEN IN
SUB-SAHARAN AFRICA TO BE
RANDOMIZED ON TO M ON TA MOVE VD
MICROBE SIDES. SHE'S WELL KNOWN
TO DIVISION OF AIDS AND TO THE
DIVISION OF MICROBIOLOGY
INFECTIOUS DISEASE. SHE'S IN
LEADERSHIP OF OUR INFECTIOUS
DISEASE CLINICAL RESEARCH
CONSORTIUM. SO WE ARE VERY
EXCITED SHE'S COMING AND HAS
INTEREST IN OUR SCIENCE. AND WE
ARE REALLY LOOKING FORWARD TO
THE NEXT ERA OF NIAID MOVING
RESEARCH FORWARD INTO HER
LEADERSHIP. SO JUST A FEW OTHER
RESULTS THAT HAVE COME OUT
RECENTLY, WE CONTINUED TO
PUBLISH ON THE RESULTS OF THE
COVALE TRIAL WHICH I MENTIONED
BEFORE IN THESE AFTERNOON
SESSIONS OF THE DMID SUB COUNCIL
MEETINGS. THERE IS A RECENT
PUBLICATION IN NATURE MEDICINE
THAT -- THIS WAS A TRIAL
DESIGNED TO COMPARE ALL -- MANY
DIFFERENT COMBINATIONS OF
BIVALENT AND MONOVALENT SARS
COV-2 VARIANT VACCINES. SOME OF
THE DATA GENERATED THROUGH THIS
TRIAL LED TO THE REALIZATION
THAT AT THE CURRENT TIME WE NO
LONGER NEEDED TO INCLUDE THE
PROTOTYPE VACCINE, THE PROTOTYPE
VALENT IN FUTURE UPDATED
VACCINES. SO THIS LED TO THE
DECISION IN PART THIS LED TO THE
DECISION FOR THE NEXT UPDATED
VACCINE TO BE MONOVALENT
DERIVATIVE OF OMICRON. THEN WE
CONTINUE TO HAVE A LOT OF
EFFORTS FOCUSED ON SARS COV-2.
THERE ALWAYS WAS A REPORT COMING
OUT OF -- COMING IN NATURE
COMMUNICATIONS FROM OHIO STATE
UNIVERSITY, INVESTIGATORS THAT
INTERESTINGLY WE KNOW THAT THIS
VIRUS IS EVOLVING AND CHANGING.
AND WE KNOW THAT THERE IS ALWAYS
POTENTIAL FOR MORE ZOONOTICS
EVENTS FROM BACK INTO HUMAN SO
IT WAS INTERESTING TO NOTE THE
FINDING THERE IS A LOT OF WHITE
TAIL DEER INFECTED WITH SARS
COV-2 AND SEEMS AS THOUGH THE
VIRUS EVOLVES MUTATES AN EVOLVES
TO NEW VARIANTS THREE TIMES
FASTER THAN THEY DO IN PEOPLE.
SO ALWAYS POTENTIAL FOR LEARNING
NEW THINGS AND THERE MIGHT BE
NEW RESERVOIRS FOR NEW SPILL
OVER EVENTS OUT THERE THAT WE
NEED TO CONTINUE TO WATCH. SO
THIS IS JUST AN INTERESTING
LICENSURE OF A DMID, A VACCINE
FORELIMB DISEASE THAT DMID
SUPPORTED THE DEVELOPMENT OF.
BUT IT IS DIFFERENT THAN THE
WAYS WE HISTORICALLY -- THAN THE
TARGET OF OUR MUTUAL VACCINES.
THE USDA, NOT THE FDA, THE
UNITED STATES DEPARTMENT OF
AGRICULTURE CONDITIONALLY
LICENSED A VACCINE FOR BAITING
MICE DESIGNED TO INTERRUPT THE
TRANSMISSION CYCLE OF
(INAUDIBLE). DMID SUPPORTED
INVESTIGATORS WORKING ON THIS
FOR OVER A DECADE. THE IDEA IS
THIS IS -- THIS INFECTION, THIS
PATHOGEN HAS A COMPLICATED LIFE
CYCLE M. MAJOR IMPLICATION --
AMPLIFICATION STEP IN NATURE IS
THE WHITE FOOTED DEER MOUSE
WHICH IS SHOWN THERE ON THE --
IN THE RIGHT PANEL. THE REASON
THAT THAT IS SUCH AN IMPORTANT
AMPLIFICATION STEP YOU CAN LOOK
AT THE MIMPS ON THE EAR OF THE
MOUSE. NYNPH IN THE GRASS WITH
THE BABY MICE RUNNING AROUND OR
ADULT MICE RUNNING AROUND,
ATTACHES TO A BODY PART THE EAR
DOESN'T HAVE A LOT OF HAIR SO
EASY TO LATCH ON TO. IF THE
MOUSE IS -- MICE BECOME
CHRONICALLY SPY ROW KITEMIC SO
THE BLOOD FEED OF THE NYNPM
WHICH IS THE EXCODE OF THE TICK,
GAVE US THE LYM DISEASE, THEY
PICK IT UP BECAUSE THEY LAND AND
START FEEDING ON THE BLOOD OF
INFECTED MOUSE THEY BECOME
INFECTED THEMSELVES, AND THEN
PROGRESS TO ADULT TICK THAT CAN
BITE A HUMAN OR CAN BITE A DEER.
AND TRANSMIT LYM DISEASE. THE
IDEA HERE IS THAT VACCINATING
THE MICE WITH THIS ORAL BAIT BY
SETTING TRAPS LIKE THAT AROUND
THE PERIMETER OF YOUR HOUSE OR
WHEREVER MICE ARE, YOU CAN
REDUCE THE SPY ROW KEITH IN THE
THE MOUSE TRANSLATION AND
PERHAPS INTERRUPT THE
TRANSLATION OF THE
(INDISCERNIBLE) TO HUMANS.
THERE IS DATA THAT SUPPORTED
THIS, THROUGH GRANTS WE FUNDED
AND WE ARE HOPEFUL THAT WE
CONTINUE TO MOVE THINGS FORWARD
IN THIS AREA PREVENTING LIME
DISEASE, THERE IS ALSO A HUMAN
VACCINE IN DEVELOPMENT IN THE
PRIVATE SECTOR SO HOPEFULLY WITH
THAT IF THAT MOVES FORWARD TO
LICENSURE THAT IS MORE TOOLS IN
THE TOOLBOX TO PREVENT SPREAD OF
LIME DISEASE. IN THE PAST FEW
MONTHS WE MADE NEW AWARDS TO
DEVELOP COHORT. TO ACCELERATE
DIAGNOSE -- DEVELOPMENT OF
DIAGNOSTICS AND VACCINES FOR
BACTERIAL SEXUALLY TRANSMITTED
INFECTION. THESE FOCUSED ON
CHLAMYDIA, GONEEE AND SYPHILIS.
I THINK THAT IS IMPORTANT TO --
THIS IS AN UNDERSERVED NEGLECTED
AREA PARTICULARLY THAT DISEASE
OF SYPHILIS, SO WE ARE HOPEFUL
DISCOVERIES THAT COME OUT OF
COHORT TO MAKE MORE PROGRESS IN
THIS AREA. WE CONTINUE TO BE
CONCERNED ABOUT THE HIGH PATH
AVIAN INFLUENZA A VIRUS
CIRCULATING AROUND THE GLOBE OUR
CREED NETWORK WORKED IN
COLLABORATION WITH OUR SERE
NETWORK BEING FOCUSED ON
INFLUENZA. TO CHARACTERIZE THE
VIRUSES THAT SEEM TO BE KILLING
MARINE MAMMALS ON THE COAST OF
PERU. THEY FOUND THAT THE
VIRUSES WERE RAPID WILL I
OCCURRING MUTATIONS, TRY TO
CHARACTERIZE IN A WAY TO
IDENTIFY THE ADAPTATIONS THAT
SEEM PARTICULARLY DANGEROUS FOR
MAMMALS SO WE CAN PREDICT --
IDENTIFY IN ADVANCE WHAT MIGHT
BE A THREAT TO HUMANS. THIS WAS
IMPORTANT RESEARCH, THIS
CONTINUES TO BE A PROBLEM THAT
EGG SHORTAGE EARLIER IN THE YEAR
SOMETHING THAT PASSED BUT
CONTINUE TO BE A THREAT TO
POTENTIAL THREAT TO HUMAN HEALTH
THIS TYPE INFLUENZA, H 5N 1
STILL CIRCULATING AROUND THE
GLOBE. THIS WAS SOMETHING DR.
AUCHINCLOSS MENTIONED IN HIS
REMARKS EARLIER TODAY. THERE IS
A REGUEST FOR INFORMATION
PUBLISHED LAST WEEK ON CHANGES
TO THE POLICY FOR OVERSIGHT OF
DUAL USE RESEARCH OF CONCERN.
AND POTENTIAL PANDEMIC PATHOGEN
OVERSIGHT, THE P 3CO POLICY
FRAMEWORK. THIS IS THE EFFORT TO
REVISE THESE POLICIES WAS
PRIMARILY UNDER -- IT WAS
RESPONSIBILITY ASSIGNED TO
OFFICE OF SCIENCE AND
TECHNOLOGY, OSTP OUT OF THE
WHITE HOUSE AND NATIONAL
SECURITY COUNCIL. THE PROPOSED
POLICY WILL EXPAND PRETTY
SIGNIFICANTLY THE NUMBER OF
PATHOGENS THAT HAVE TO BE ON THE
DURC WATCH LIST. THIS IS MY READ
OF THE DRAFT POLICY, THE DRAFT
POLICY ISN'T PUBLISHED IN THE
FEDERAL GUIDE OR FEDERAL
REGISTRY BUT A LOT OF QUESTIONS
ON AREAS OF -- THAT MIGHT BE
UNCLEAR OR DIFFICULT TO
IMPLEMENT ARE TARGETED QUESTIONS
ARE ASKED SO BY OCTOBER 16TH
OSTP AND THE NATIONAL SECURITY
COUNCIL WOULD LIKE TO GET INPUT
FROM THE SCIENTIFIC COMMUNITY,
PEOPLE THAT ARE INVOLVED IN
BIOSAFETY AT THE INSTITUTIONAL
LEVEL AND INVESTIGATORS WHO WORK
WITH SOME OF THESE PATHOGENS TO
GET INPUT HOW THIS POLICY MAYBE
COULD BE IMPROVED TO MAKE IT
WORKABLE IN MANY THE FUTURE. SO
THAT'S OUT THERE. IT IS
IMPORTANT. IF YOU DON'T THINK
YOU ARE A STAKEHOLDER, YOUR
INSTITUTIONAL BIOSAFETY
COMMITTEE MIGHT WANT TO BE --
YOU MIGHT POINT THEM TO THIS RFI
SO THAT POLICY THAT COMES OUT ON
THE OTHER SIDE TO BE IMPLEMENTED
NEXT YEAR IS THE BEST IN TERMS
OF BIOSECURITY BIOSAFETY AND
SUPPORT IT IS BEST SITES. SO
THAT CONCLUDES MY REMARKS. I
WILL HAND OFF THE PODIUM TO DR.
JUDY HEWITT WHO WILL TALK ABOUT
WHO WILL GIVE BACKGROUND ON
PRE-CLINICAL SERVICES, THE SUITE
OF PRE-CLINICAL SERVICES THAT
DMID SUPPORTS.
>>THANK YOU, EMILY. APPRECIATE
YOU MAKING TIME IN THE AGENDA
FOR US. SO I WILL START BY
DESCRIBING OUR PRE-CLINICAL
SERVICES AND THE TITLE OF THIS
SLIDE ALSO INCLUDES RESEARCH
RESOURCES AND WE WILL GET INTO
THAT IN A SECOND. THE POINT IS
THAT TO PROVIDE A SUITE OF
CAPABILITIES TO ADDRESS PRODUCT
DEVELOPMENT GAPS. ALONG THE
BOTTOM WE HAVE CONSIDER RESEARCH
RESOURCE, PRE-CLINICAL MODELS OF
INFECTIOUS DISEASE THAT CAME AS
A CONCEPT TO YOU, I THINK TWO
YEARS AGO, AS WELL AS THE BEI
RESOURCES RESEARCH -- RESOURCE
REPOSITORY. SO YOU HAVE APPROVED
THOSE AND THOSE ARE IN THE
PROCESS OF BEING AWARDED. THEN
WE HAVE VARIOUS SERVICES FOR
THERAPEUTICS, VACCINES, OR
DIAGNOSTICS. SO THE
BIOPHARMACEUTICAL PRODUCTS IS
ALSO BEING AWARDED AS WE SPEAK.
SO YOU HAVE HEARD THAT WITHIN
THE PAST TWO YEARS. IN VITRO
ASSESSMENT OF ANTIMICROBIAL
ACTIVITY WILL COME TO YOU NEXT
YEAR. THEN TODAY YOU ARE GOING
TO HEAR ABOUT THREE SPECIFIC
CONCEPTS THE NON-CLINICAL
SERVICES FOR INTERVENTIONAL
AGENTS AS WELL AS VACCINE
EVALUATION AND TESTING AND
MANUFACTURING. SO I WON'T SAY
ANYTHING MORE ABOUT THOSE. THEN
LASTLY, WE NEED TO POINT OUT
THIS YEAR WE AWARDED A
PRE-CLINICAL SERVICE PROGRAM FOR
DIAGNOSTICS. SO THIS IS BRAND
NEW, WE ARE LOOKING TO SOLICIT
REQUESTS FROM THE RESEARCH
COMMUNITY WHERE THEY NEED HELP
DEVELOPING DIAGNOSTICKICS. SO
BRIEFLY I WILL MENTION THAT,
HELP WITH PRODUCT DEVELOPMENT
PROCESSES, IMMUNOASSAYS, SAMPLE
PREP VARIOUS CAPABILITIES LIKE
THAT. ALL THESE SERVICES WERE
SET UP IN P RESPONSE TO
BIODEFENSE INITIATIVES EARLY ON
PREACCEPT AT A TIMED BY AD
EVENTS OF 22 YEARS AGO TODAY AND
THE ANTHRAX LETTERS, AS THEY
WERE RECOMPETED THEY BECAME LESS
FOCUSED ON BIODEFENSE AND
FOCUSED ON PATHOGENS THAT DMID
WORKS ON. THESE ARE AVAILABLE TO
FOR ALL CAPABILITIES. WE ALWAYS
USE THESE PRE-CLINICAL SERVICES
WHENEVER THERE WERE IS AN
OUTBREAK SO WANTED TO HIGHLIGHT
THAT NOT ONLY HELPING THE
DEVELOPERS IT IS PART OF OUR
RESPONSE EFFORT TO EVALUATION OF
INTERVENTIONS WHEN THERE IS AN
OUTBREAK. SO THE PRE-CLINICAL
SERVICES OBVIOUSLY PROVIDE
PRE-CLINICAL SERVICES BUT I WANT
TO HIGHLIGHT OTHERS THINGS THEY
DO SO THEY LOWER THE RISK FOR
DEVELOPERS WE PROVIDE EXPERTISE
CAPABILITY AND PRODUCT
DEVELOPMENT FROM OUR STAFF
EXPERTISE AND CAPABILITY THE
PROPERTY TORRS PERFORMING THESE
SERVICES PROVIDE ADDITIONAL
CAPABILITIES AND THE
CAPABILITIES PERFORMING THE
WORK. WE HOPE TO MOVE PROMISING
DISCOVERIES ALONG THE PRODUCT
DEVELOPMENT PATHWAY. THIS IS
INTENDED TO BE A GAP FILLING
SERVICE, NOT INTENDED TO BE A
FULL PRODUCT DEVELOPMENT PROGRAM
SOUP TO NUTS, REALLY OUR INTENT
IS THAT WE CAN HELP
INVESTIGATORS OUT, GET THEM SOME
CRITICAL KEY PIECES OF DATA TO
ATTRACT FUNDING FROM OTHER
SOURCES. LASTLY, WHEN WE
PERFORM THESE SERVICES WE DO IT
UNDER AGREEMENTS THAT ASSURE THE
CONFIDENTIALITY AND PROTECT
INTELLECTUAL PROPERTY OF THE WHO
PRODUCT DEVELOPER. SO THIS SLIDE
SUMMARIZES WHO IS ELIGIBLE. EVE
INNOVATORS FROM ACADEMIA,
NON-PROFIT INDUSTRY AND
GOVERNMENT. INDUSTRY IN TERMS OF
AGREEMENTS WITH VARIOUS
ORGANIZATIONS INDUSTRY TAKES UP
THE BULK OF OUR AGREEMENT,
APPROXIMATELY 55 PERCENT OF OUR
AGREEMENTS ARE WITH INDUSTRY. I
WOULD SAY THAT IS LARGELY SMALL
COMPANIES. THERE ARE
OCCASIONALLY LARGE PHARMA
REQUESTERS. FOLLOWED BY
ACADEMIA, 30% REQUEST COME FROM
ACADEMIC INVESTIGATORS AND
BALANCE FROM INDUSTRY OR OTHER
GOVERNMENT AGENCIES. WE CAN
PROVIDE THESE SERVICES TO BOTH
DOMESTIC AND FOREIGN
INSTITUTIONS, THOUGH FAR AND
AWAY IT WAS LARGELY DOMESTIC.
THERE IS NOT A REQUIREMENT YOU
HAVE NIH FUNDING TO ACCESS
SERVICES, THE HOPE IS YOU WOULD
USE RESULTS TO ATTRACT NIH
FUNDING. IN A FEW SLIDES I WILL
SHOW YOU SIMPLIFIED REQUEST
PROCESS, WHEN I GET TO THE SLIDE
MAY NOT LOOK IT BUT COMPARED TO
APRYIA-- APPLYING FOR GRANT IT A
SIMPLIFIED PROCESS, AVAILABLE
YEAR ROUND. WE HAVE SOME THIS
LAST BULLET TALKS HOW WE
DETERMINE WHICH PROJECTS TO
SUPPORT. THIS IS VERY HIGH LEVEL
BUT I HAVE ANOTHER SLIDE THAT
GETS INTO A LITTLE MORE DETAIL
ON THAT. SO IT IS IMPORTANT TO
MENTION ALL THE CONTRACTS THAT
PROVIDE PRE-CLINICAL SERVICES
ARE WHAT IS KNOWN AS INDEFINITE
DELIVERY AND DEFINITE --
INDEFINITE QUANTITY OR IDIQ
CONTRACTS. WHAT THAT MEANS IS
THE GOVERNMENT KNOWS WE ARE
GOING TO NEED SOME OF THIS, WE
DON'T KNOW HOW MUCH OR WHEN. SO
WHEN WE BRING CONCEPTS TO YOU IT
IS DEVELOPING A POOL OF
CONTRACTORS WHO CAN PROVIDE
VACCINE TESTING OR
INTERVENTIONAL AGENT TESTING. SO
THEY GET A BASE CONTRACT THAT
ALLOWS US TO PLACE TASK ORDERS
FOR SEVEN YEAR ORDERING PERIOD.
SO THAT BASE CONTRACT IS REALLY
SOMETHING LIKE A FISHING
LICENSE. YOU ARE ALLOWED TO
FISH, DOESN'T MEAN YOU ARE GOING
TO CATCH ANYTHING. SO WHEN WE
HAVE A SPECIFIC REQUEST FOR A
TASK ORDER WE PUT THAT REQUEST
OUT TO THE CONTRACTORS IN THE
POOL, THE CROs THAT HAVE
FISHING LICENSES AND THEY
COMPETE WITH EACH OTHER TO GET
THAT WORK. ALTS THAT POINT WE
ARE FOCUSING ON WHO HAS THE BEST
CAPABILITY TO PERFORM THE
SPECIFIC WORK WE ARE LOOKING TO
CONTRACT. THEY GET A GUARANTEED
MINIMUM WE USE FOR INITIAL KICK
OFF MEETING. THEN THERE IS ALSO
A SPECIFIED MAXIMUM VALUE FOR
CONTRACTS WHICH ARE EXTREMELY
LARGE WITH THE HOPE IF
ADDITIONAL MONEY CAME TO US FOR
OUTBREAK RESPONSE FOR EXAMPLE WE
WOULD BE ABLE TO INCREASE THE
VALUE OF THESE CONTRACTS. SO
THE REAL FUNDING COMES WITH THE
INDIVIDUAL TASK ORDERS AS THEY
COMPETE FOR THOSE. THIS IS THE
BUSINESS SLIDE. THE TITLE SAYS
PRE-CLINICAL SERVICES PROVIDE
SUPPORT NOT FUNDING SO IT IS
REALLY IMPORTANT TO UNDERSTAND
THIS IS IN KIND SUPPORT FOR THE
EXTERNAL REQUESTERS, WE DON'T
GIVE THEM THE FUNDING DIRECTLY.
WE ARE FUNDING OUR CONTRACTORS
WHO ARE PROVIDING THE SERVICES.
SO I'M SHOWING AGREEMENTS
VARIOUS STAKEHOLDERS IN THEIR
ROLES AND DELIVERABLES. SO I
WILL START WITH REQUESTER WHO
COMES TO US TO MAKE A REQUEST
FOR A PARTICULAR SERVICE. THEY
TALK WITH DMID STAFF, FREQUENTLY
THEY GO TO PROGRAM OFFICER
FIRST. BUT MIGHT KNOW WHO THE
STAFF RUNNING THE VACCINE
TESTING CONTRACT IS SO THEY
MIGHT APPROACH THAT PERSON, IT
JUST DEPENDS. SO A TEAM OF DMID
PEOPLE GET TOGETHER AND TALK
WITH THAT REQUESTER ABOUT THEIR
REQUEST. WE BRING SUBJECT MATTER
EXPERTS OR SMEs AS NEEDED,
SUCH AS GMP TOX STUDIES OR
MANUFACTURING, WE BRING THAT
EXPERTISE, WE BRING IN
REGULATORY AFFAIRS STAFF NEEDED
DEPENDING ON WHAT THE REQUEST
IS. SO THE DMID TEAM WILL
DISCUSS REQUEST WITH THE
REQUESTER, AND THIS CAN BE
SOMETHING OF ITERATIVE PROCESS.
IF WE THINK WE WANT TO MOVE
AHEAD WE WILL ASK REQUESTER TO
HAVE INSTITUTION SIGN NCEA OR
NON-CLINICAL EVALUATION
AGREEMENT. LIKE A MATERIAL
TRANSFER AGREEMENT. IT SPECIFIES
WHO HAS PUBLICATION RIGHTS,
PROTECTS THE INVESTIGATORS IP,
CONFIDENTIALITY, ALL KINDS OF
THINGS LIKE THAT. THERE IS A
SECOND PART TO THE AGREEMENT
CALLED SRF OR SERVICE REQUEST
FORM WHERE WE GET INTO THE
NITTY-GRITTY OF WHAT IS THE
SERVICE THE REQUESTERS ACTUALLY
REQUESTING AND WHAT WE ARE
AGREEING TO PROVIDE. T MORE THE
SCIENCE TECHNICAL ASPECT OF THE
REQUEST. SO WHAT HAPPENS WHEN
THERE MIGHT BE SEVERAL
DISCUSSIONS TO COME TO A
DECISION WHAT IS THIS REQUEST
LOOK LIKE AND THEN THE DMID TEAM
WILL PUT TOGETHER A REQUEST FORM
THAT GOES TO WHAT I HAVE CALLED
DMID LEADERSHIP REVIEW I WILL
DESCRIBE IN MORE DETAIL. FIRST
STEP IS GETTING BRANCH CHIEF TO
OKAY IT. THEN IT GOES TO PCS
REVIEW COMMITTEE. MADE UP OF
KRISTINA (INAUDIBLE) THE DEPUTY
DIRECTOR, THE DIRECTOR DEPUTY
DIRECT DOOR AND THREE SCIENTIFIC
SENIOR SCIENTIFIC OFFICERS ONE
FOR VACCINES ONE FOR
THERAPEUTICS AND ONE FOR
DIAGNOSTICS. THESE ARE
INDEPENDENT FOLKS THAT DON'T
HAVE A GRANT OR CONTRACT
PORTFOLIO OF THEIR OWN BUT THEY
HAVE DEEP EXPERIENCE IN PRODUCT
DEVELOPMENT IN THEIR VARIOUS
AREAS. SO AS A COMMITTEE WE
DISCUSS THE REQUESTS THAT ARE
BROUGHT TO US EACH WEEK. WE
AGREE WHICH SHOULD MOVE FORWARD
LASTLY THE DIVISION DIRECTOR DR.
ERBELDING SIGNS OFF REQUESTS WE
PUT FORWARD TO HER. THAT PROCESS
HAPPENS EVERY WEEK. ONCE THE
OKAY IS GIVEN FOR PARTICULAR
PROJECT, SO WHAT THAT OKAY
REALLY GRANTS IS THE FUNDING
ATTACHED TO THAT SPECIFIC
PRODUCT. OR PROJECT. SO WE THEN
ATTACH THAT REQUEST TO A TASK
ORDER. SOMETIMES WE HAVE TASK
ORDERS ALREADY AWARDED AND I
WILL GIVE YOU A GOOD EXAMPLE OF
WHERE WE MIGHT DO THAT,
SOMETHING LIKE A SCREENING TASK
ORDER. SO WHERE WE KNOW WE WANT
TO HAVE SCREENING FOR ANTIVIRALS
FOR SARS COV-2. SO WE SET UP A
TASK ORDER THAT DOES THAT
ACTIVITY. THE APPROVAL COMES AT
THE BRANCH CHIEF LEVEL. IF WE
GET A REQUEST FOR GMP
MANUFACTURING OF THE VACCINE
THAT IS GOING TO COST MORE
MONEY, THEN WE WILL SET UP A
TASK ORDER SPECIFICALLY TO DO
THE GMP MANUFACTURING FOR THAT.
SO WE WILL SET UP A NEW TASK
ORDER AND THE CONTRACT OR TASK
ORDER IS THE AGREEMENT THAT
ALLOWS US TO GET A THAT WORK
DONE BY A CONTRACT RESEARCH
ORGANIZATION THAT WE HAVE SOME
ACADEMIC ORGANIZATIONS THAT CAN
ALSO DO THIS FOR US. SO ONCE WE
HAVE AGREED TO DO THE WORK THEN
WE WILL HAVE TELECONS THAT
INCLUDE DMID TEAM, REQUESTER AND
THE CRO ALL TOGETHER TALKING
ABOUT THE NATURE OF THE WORK, WE
GET FEEDBACK ON THE DATA. THEN
EVENTUAL REPORT THAT COMES FROM
THE STUDY IS SHARE WITH THE
REQUESTER AND REPORT BECOMES THE
PROPERTY OF THE REQUESTER, THEY
GET TO USE THAT AS THEY SEE FIT
SO THAT IS OUR PROCESS. NOT
EXACTLY -- IT CAN BE ITERATIVE,
IT DEPENDS ON THE NATURE OF
REQUEST WHEN IT COMES TO US.
MANY TIMES PEOPLE COME TO US FOR
EXAMPLE ASKING FOR GMP
MANUFACTURING BECAUSE THEY KNOW
THAT'S A GAP IN THEIR PROGRAM.
WHEN WE TALK TO THEM WE LEARN
ABOUT THE DATA, WE MIGHT FIGURE
OUT THERE'S SOMETHING CRITICAL
THEY NEED BEFORE THEY GET TO GMP
MANUFACTURING AND WE WILL
PROVIDE THAT SERVICE INSTEAD. IT
IS A DISCUSSION PROCESS. I'M
GOING TO CALL OUT ON THE DMID
TEAM, WE HAVE PRODUCT
DEVELOPMENT SPECIALISTS, LOCATED
IN EACH SCIENTIFIC BRANCH. SO
THOSE ARE THE PEOPLE THAT OFTEN
SHEPHERD REQUEST THROUGH THIS
PROCESS. SO THEY HAVE GAIN AD
LOT OF EXPERIENCE WITH PRODUCT
DEVELOPMENT AS THEY PUT MORE OF
THESE REQUESTS THROUGH THE
PROCESS. WE FIND THIS PROCESS
HAS BEEN GOING ON FOR PROBABLY
OVER A DECADE WHEN WE REALLY
EXPANDED THE ACCESS TO THESE
RESOURCES TO ALL OF DMID COVERED
PATHOGENS. SO A STAFF AND
PRODUCT DEVELOPMENT SPECIALISTS
HAVE GOTTEN USED TO THESE
REQUESTS, THEY ARE DOING MORE
WORK ON THE FRONT END PUT IN
DEVELOPING GOOD REQUESTS. SO I
JUST WANTED TO SAY THAT IN A WAY
TO SAY THAT WE DON'T GET A LOT
OF REQUESTS THAT COME ALL THE
WAY TO COMMITTEE TO BE DENIED.
THEY ARE OFTEN REFINED OR
POTENTIALLY SENT BACK TO THE
BRANCH FOR REFINEMENT BUT WHEN
IT COMES TO COMMITTEE THEY ARE
USUALLY IN GOOD SHAPE. HERE ARE
THE CRITERIA THE PCS COMMITTEE
DISCUSSES WHEN WE ARE LOOKING AT
A REQUEST. INITIALLY IS IT
WITHIN OUR MISSION, DO WE HAVE
THE CONTRACT SERVICES THAT CAN
PROVIDE WHAT REQUESTER IS ASKING
FOR, DO THEY HAVE THE PRODUCT
AVAILABLE IN ORDER TO ACCOMPLISH
THE PROJECT. NUMBER FOUR HERE IS
IN COMPLIANCE WITH THE ANIMAL
WELFARE REGULATION. SO I WILL
JUST GIVE AN EXAMPLE OF ONE
THING WE MIGHT LOOK AT THAT SO
IF SOMEONE REQUESTS A NON-HUMAN
PRIMATE STUDY, WE LOOK AT THE
BODY OF DATA, THE SMALL ANIMAL
DATA THAT SUPPORTS MOVING TO
NON-HUMAN PRIMATES AND DECIDE
WHETHER WE THINK THAT IS A
SUFFICIENT BODY OF EVIDENCE FOR
MOVING FORWARD OR IF THEY NEED
MORE SMALL ANIMAL DATA. WE
CONSIDER THE REQUEST WHETHER THE
REQUESTER HAS OTHER SUPPORT THAT
CAN FUND THIS PROJECT, WHETHER
FIRST REQUEST OR REPEAT REQUEST.
I WILL SAY MORE ABOUT THAT.
AGAIN WHETHER SUPPORTED BY
ADEQUATE PRELIMINARY DATA, THEN
WE TALK ABOUT GENERAL THINGS
LIKE THE LIKELIHOOD OF
CONTRIBUTING PRODUCT
DEVELOPMENT, IN OTHER WORDS DO
THEY HAVE A PLAN TO CARRY THIS
PRODUCT FORWARDS? IS THIS
PRODUCT IMPACTFUL TO PUBLIC
HEALTH? IS IT GOING TO IMPROVE
UPON EXISTING PRODUCTS. IS IT A
HIGH PRIORITY FOR NIAID. SO
THOSE ARE THINGS WE DISCUSS WHEN
TALKING ABOUT THE REQUEST. SO WE
DO OUR BEST TO MAKE SURE THAT
EVERYONE IS AWARE OF THESE
PRE-CLINICAL SERVICES, SO AS I
MENTIONED EARLIER PEOPLE'S
PROGRAM OFFICER IS OFTEN THEIR
FIRST STOP. WE ALSO DO HAVE ALL
THESE MAILBOXES SO YOU CAN
CONTACT STAFF AND IF SOMEONE IS
OUT SOMEONE ELSE WILL ANSWER THE
MAIL. WE HAVE ONE OF THOSE FOR
EACH OF THE SERVICES. WE ALSO
HAVE A RESEARCHER RESOURCES FOR
RESEARCHERS WEB PAGE FOR NIAID.
FOR NIAID AT LARGE THERE ARE
MANY, MANY RESOURCES THERE,
SUGGEST AS YOU FILTER ON
PRE-CLINICAL SERVICES AND DMID
YOU WILL COME UP WITH THESE FIVE
SERVICES THAT ARE LISTED HERE.
SO THERAPEUTIC AND VACCINE
DEVELOPMENT SERVICES ARE WHAT
YOU ARE GOING TO HEAR ABOUT
LATER TODAY. STAFF ARE
CONSTANTLY PRESENTING ABOUT
THESE PRE-CLINICAL SERVICES AS
THEY ARE GOING TO CONFERENCES,
AND WORKSHOPS, EITHER ORAL
PRESENTATIONS OR POSTERS, AND
THIS IS JUST AN EXAMPLE. WE HAVE
A BROCHURE, THIS IS FOR
ANTIVIRAL PROGRAM FOR PANDEMICS.
WE DEVELOPED A BROCHURE THAT
GETS TO A LITTLE BIT MORE DETAIL
ABOUT THE ACTUAL SERVICES THAT
WE ALREADY HAVE UNDER CONTRACTS.
THAT IS JUST A LITTLE SNAP SHOT
OF THAT. THAT IS THE END OF MY
PRESENTATION I WILL MAKE ONE
LAST COMMENT. WE WORK WITH OTHER
PARTNERS FOR EXAMPLE CARBAX OR
SEPE, WE CAN'T GIVE THEM OUR
FUNDS FOR THEM TO SPEND ON THEIR
PROGRAMS, BUT WE USE OUR
PRE-CLINICAL SERVICES THE ONCE
AGAIN PROVIDE IN KIND RESOURCES
TO INVESTIGATORS THAT CARVAX AND
SEPE AND OTHER STAKEHOLDERS ARE
FUNDING. SO WITH THAT I WILL
CLOSE AND TAKE ANY QUESTIONS.
WE CAN MAKE SURE OF THAT,
PROBABLY NOT THIS EXACT SLIDE
SET BUT WE DO HAVE A MORE
COMPREHENSIVE SET OF SLIDES WE
HAVE PREPARED FOR STAFF TO PICK
AND CHOOSE FROM GOING FROM
VARIOUS MEETINGS. SOME OF THESE
SLIDES YOU SAW TODAY WERE NEWER
REFUNDS SO WE WILL MAKE SURE
THEY ARE AVAILABLE.
(OFF MIC)
>>GOOD AFTERNOON. TODAY I WILL
TALK ABOUT TWO CONCEPTS FOR
APPROVAL, THE INTERVENTIONAL
AGENTS FOR SAFETY AND
PHARMACOKINETICS SERVICES AND
INTERVENTIONAL AGENTS FOR
CHEMISTRY SERVICES. THE
OBJECTIVE OF THESE SERVICES ARE
TO PROVIDE DIVERSE SUITE OF
SERVICES TO SUPPORT
THERAPEUTICS, PRODUCT
DEVELOPMENT FROM EARLY LEAD
OPTIMIZATION TO ENABLING
STUDIES. THANK YOU, DR. HEWITT
FOR GIVING ME A GREAT OVERVIEW
BECAUSE IT SAVED ME QUITE A BIT
OF TIME. THE SAFETY AND
PHARMACOKINETIC SERVICES INCLUDE
PRODUCT DEVELOPMENT PLANNING IN
VITRO ABSORPTION, DISTRIBUTION,
METABOLISM, EXCRETION,
TOXICOLOGY. IN VITRO
PHARMACOKINETICS OR PK SAFETY
AND TOXICOLOGY. THE CHEMISTRY
SERVICES ARE GOING TO INCLUDE
MEDICINAL CHEMISTRY SYNTHESIS
PROCESS CHEMISTRY OPTIMIZATION,
PREPARATION TOXICOLOGY BATCHES,
GMP MANUFACTURING AS WELL AS
DRUG SUBSTANCE AND DRUG PRODUCT
RELEASE AND STABILITY TESTING.
THIS IS A NEW CONCEPT, THESE TWO
NEW CONCEPTS WILL FOLLOW A SEVEN
YEAR IDIQ AND THE ANTICIPATED
NUMBER OF AWARDS FOR THE
CHEMISTRY SERVICE IS
APPROXIMATELY SIX AND FOR THE
SAFETY AND PHARMACOKINETIC
SERVICES APPROXIMATELY 12. SO
GRAPHICS SHOWING MANY WAYS BUT
DRUG DEVELOPMENT IN GENERAL VERY
COMPLEX LENGTHY RISKY COSTLY, ET
CETERA. WE SEE ATTRITION IN THE
EARLY PARTS OF THE PATHWAY IN
THE VALLEY OF DEATH. SO WE
REALLY NEED TO FIND GOOD WAYS TO
MITIGATE THIS RISK BY PROCURING
PROJECTS EARLY. THIS DIAGRAM
SHOWS OVERALL DRUG DEVELOPMENT
FOR THERAPEUTIC AREAS IN THE
ANTI-INFECTED SPACE YAHOO SEE
HIGH ATTRITION RATE IN THE
VALLEY OF DEATH SO TO SPEAK.
THIS THEN CAUSES LATER PRODUCTS
TO HAVE HIGHER CHANCE OF SUCCESS
BECAUSE CLINICAL MODEL OR
PRE-CLINICAL MODELS ARE CLOSELY
RELATED TO WHAT WE SEE IN THE
CLINIC. SO THERE IS AN EVEN
BIGGER NEED FOR PRE-CLINICAL
SERVICES FOR ANTI-INFECTIVES.
SO THIS SLIDE ILLUSTRATES WHERE
DIFFERENT PARTS OF DMID FOCUS
OVERLAP WITH THE PRODUCT
DEVELOPMENT PATHWAY. THE
PRE-CLINICAL SERVICES ARE USED
FOR AS YOU HEARD E TERM
ORGANIZATIONS BUT ALSO INTERNAL,
THEY HAVE BEEN USED TO SUPPORT
GRANTS, PRODUCT DEVELOPMENT
CONTRACTS PHASE 1 CLINICAL
SERVICES SO FOR TODAY WE WILL
TALK ABOUT THE BOX IN GREEN,
PRE-CLINICAL SERVICES. AS YOU
HEARD DR. HEWITT SAY, WE SHARE
OUR SUBJECT MATTER EXPERTISE AND
SUPPORT EXTERNAL REQUESTERS WITH
THESE GAP FILLING PRE-CLINICAL
SERVICES TO DERISK THERAPEUTIC.
THESE ARE IN THIS CASE SMALL
MOLECULES NATURAL PRODUCTS SMALL
PEPTIDES, OTHER ITEMS FALL UNDER
THE OH PRE-CLINICAL SERVICES
THAT WE OFFER TO SUPPORT
PROGRAMS. THESE ARE ALL USED TO
SUPPORT PROJECTS THAT ARE
TARGETING NIAID PATHOGENS OF
INTEREST. THE TAKE AWAY FROM
THIS SLIDE I WILL REFER TO LATER
IS FIVE DIFFERENT TASK AREAS IN
THE CURRENT PRE-CLINICAL
SERVICES. TASK AREAS A THROUGH
E, A IS PRODUCT DEVELOPMENT
PLANNING, PROVIDING PRODUCT
DEVELOPMENT PLAN FOR REQUESTER
AND HOW TO GET COMPOUND INTO THE
CLINIC. TASK AREA B IS DISCOVERY
SIDE OF SYNTHESIS SO MEDICINAL
CHEMISTRY SYNTHESIS OF BULK
INTERMEDIATES, TARGETS WE MAY
NEED TO ASSESS STRUCTURAL
ACTIVITY, RELATIONSHIPS TASK
AREA C IS LATER. IN THE PATHWAY,
NOW OPTIMIZING CHEMICAL
SYNTHESIS, DOING BULK -- DRUG
PRODUCT AND NON-GMP AND GMP
MANUFACTURING. TASK AREA D IS
PRE-CLINICAL SAFETY AND
TOXICOLOGY FOR THE MORE
COMPLICATED PHARMACOKINETIC
SERVICES, THIS INCLUDES GLP AND
NON-GLP TESTING. IN TASK AREA E
WE HAVE LEAD OPTIMIZATION FOR
ADME SAFETY AND RAPID PK, THIS
IS EARLIER ON FOR LEAD
OPTIMIZATION, THIS IS RAPID HELP
DEVELOP LEAD OFF PROGRAM TO MOVE
FURTHER IN THE PATHWAY. SO LET'S
LOOK AT KEY ACCOMPLISHMENT OUR
CURRENT ITERATION OF THE
PRE-CLINICAL SERVICES. WE HAVE
CONTRIBUTED TO EIGHT MARKETED
DRUGS. SOME OF THESE FDA
APPROVALS WERE PROJECTS DRIVEN
BY PUBLIC PRIVATE PARTNERSHIPS
OR ADVANCE NIH HHS OBJECTIVES.
OF THESE EIGHT MARKETED DRUGS,
THREE MARKETED DRUGS RECEIVED
INITIAL APPROVAL LISTED HERE AND
THE OTHERS, FIVE OTHERS RECEIVED
APPROVAL FOR NEW INDICATION
USING PCS. AN EXAMPLE HOW WE USE
SERVICES TO OVERLAP WITH OTHER
PROGRAMS FOR INSTANCE THE DRUG
DEVELOPMENT SECTION PRODUCT
DEVELOPMENT PORTFOLIO 75%
CURRENT PROJECTS RECEIVED PCS
SUPPORT AT SOME POINT PRIOR TO
AWARD. WE CAN USE SERVICES FOR
FOLKS TO COME THROUGH THE VAA
THAT HAVE PROGRAMS INTERESTING
TO OUR NEEDS. WE CAN PROVIDE
THEM PRE-CLINICAL SERVICES TO
PREPARE FOR NEXT YEAR'S VA SO
THEY ARE READY FOR A BETTER
PROPOSAL AND ULTIMATELY WE HAVE
SEEN THIS HAPPEN MANY TIME WHERE
IS SERVICES WERE KEY GAPS IN
THEIR PROPOSAL AND THEY ALL
RECEIVED FUNDING THE FOLLOWING
YEAR SO WE CAN SUPPORT OUR NEEDS
USING THE PRE-CLINICAL SERVICES
TO GET THINGS INTO PRODUCT
DEVELOPMENT. SO LET'S TALK THE
SCOPE OF OUR SUPPORT. SO
ORIGINALLY, BACK IN 2006 WE
AWARDED ALL THESE FIVE DIFFERENT
AREAS TO A SINGLE CONTRACTOR. SO
THAT CONTRACTOR NEEDED TO
PROVIDE THAT WHOLE LIST OF
SERVICES, THEY DID A GOOD JOB
BUT AS WITH E MOVE FORWARD WE
WANT TO INCREASE THE COMPETITION
AND THE DIVERSITY OF OUR
CAPABILITIES SO IN 2018 WE SPLIT
OUT EACH OF THOSE TASK AREAS
INTO THEIR OWN TARGET IF YOU
WILL WHERE WE WERE THEN GOING TO
POPULATE THAT POOL WITH
CONTRACTORS FOR ONLY THAT
SPECIFIC TASK AREA. WHAT YOU CAN
SEE IS WE LEARN AD FEW THINGS,
TASK AREA B AND C ARE NOW
HIGHLIGHTED IN RED. THIS IS THE
CHEMISTRY TASK ORDER, CHEMISTRY
AND MANUFACTURING, WE WERE
SIGNIFICANTLY LIMITED BY THE
NUMBER OF CONTRACTORS THAT CAME
IN THROUGH THAT MECHANISM.
SPECULATE LATER WHY THIS MAY
HAVE BEEN, WE NEED TO NOTE THERE
THERE WAS LIMITATIONS THERE, THE
SAFETY AND PK, A LOT OF THESE
SAFETY GLP TALKS, THESE ARE BIG
STUDIES, COSTLY STUDIES YOU WANT
A LARGE POOL TO MAXIMIZE
COMPETITION AND MAXIMIZE THE
CAPABILITIES. AS THIS PROGRAM
MOVE FORWARD NUMBER OF COMPANIES
CHANGE THEIR BUSINESS MODEL OR
THEY LOST KEY PLAYERS AND MAYBE
NO LONGER CONSIDERED EXPERTS IN
THE AREA. BECAUSE OF THAT OUR
POOLS WERE REDUCED TO TWO SO
LIMITD BY THE CAPABILITIES WE
CAN OFFER BUT NOT LIMITED TO THE
POINT THAT IT WAS DEBILITATING
BUT WOULD HAVE BEEN NICE TO HAVE
MORE. ENOUGH THE FINAL SPACE WE
SAW THAT RAPID ADME AND
PROFILING PK FOR LEAD OFF, THIS
IS A HEAVILY USED RESOURCE
BECAUSE EARLY LEAD OFF YOU
TYPICALLY HAVE A HARD TIME
FINDING CHEMISTRY BUT YOU CAN DO
A LITTLE SAR BY CATALOG IF YOU
WILL OR ANALOG BY CATALOG. BUY
IN CERTAIN SUBSTRATES TO DEVELOP
STRUCTURAL ACTIVITY
RELATIONSHIPS BUT THEY STILL
WILL NOT HAVE A WAY TO GET
PHARMACOKINETICS AND SEE IF IT
WORKS AS POTENTIAL TREATMENT INN
VIVO. ONE ORIGINAL CONTRACTORS
WAS A SPECIALIST. THIS IS ALL
THEY DID SO THEY AWARDED THE
EARLY CONTRACTS THAT WERE
AWARDED WENT ALL TO THEM. THEY
ARE CHEAPER AND PRICED EVERYBODY
ELSE ON THE MARKET. BECAUSE OF
THAT WE NO LONGER RECEIVE BID
ANYONE ELSE. THEY CAN PROVIDE
CAPABILITIES, ONLY ONE PERSON IN
THE POOL. SO LET'S LOOK AT THE
SCOPE OF SUPPORT WHAT WE WANT
GOING FORWARD. SO WE WILL RENEW
WITH THE SAME SCOPE. WE NEED TO
SEPARATE THE CHEMISTRY FROM THE
SAFETY AND PK WITH THE SAME
RATIONALE AS BEFORE TO CREATE
DEEPER AND MORE COMPETITIVE TASK
AREAS. LET'S LOOK FIRST OFF WITH
THE SAFETY AND PHARM PHARMACOKIC
SERVICES SO WE STILL PROVIDE
PRODUCT AND PLANNING BUT TAKE
TASK AREA D, GLP AND NON-GLP
TESTING WHICH LIMIT WHAT
COMPANIES CAN BUY BECAUSE IT IS
NOT VERY COMMON SO WE TAKE THAT
TASK AREA, SPLIT IT OUT TO
NON-GLP IN VITRO TESTING NON-GLP
IN I HAVE SLOW TESTING. THIS
OPENS UP THE POOL POTENTIAL
BIDDERS SIGNIFICANTLY. SO SOME
FOLKS THEY COME IN JUST IN VITRO
GLP TESTING SO OVERALL WE SEE A
HUGE INCREASE IN COMPETITION AND
CAPABILITIES AND WE WILL KEEP
GLP IN VITRO AND IN VIVO TESTING
IN ITS OWN TASK AREA. AS WE GO
DOWN THE TWO TASK AREA E WE GET
QUICK IN VITRO ADME AND PK
PROVILING, NOW WE HOPE WE CAN
ATTRACT MORE COMPANIES THAT CAN
DO FIXED FEE FOR US. THIS WILL
SIGNIFICANTLY REDUCE THE COST,
BUT ALSO INCREASE CAPACITY
BECAUSE THEY ARE OFF THE SHELF
PRODUCTS WE CAN REQUEST QUICKER
THAN WE CURRENTLY DO. MOVING
FORWARD TO CHEMISTRY SERVICES,
WE ARE GOING TO DIVIDE CHEMISTRY
SERVICES INTO SUBSECTIONS WHERE
WE WILL PUT OUT FIVE
SUBCATEGORIES OF THINGS THAT WE
ARE INTERESTED IN, AND ALLOW
FOLKS TO APPLY FOR SUBCATEGORIES
AND AS LONG AS THEY COVER THE
MAJORITY THREE, THAT WE KNOW
COULD AWARD CONTRACTS TO THOSE
THREE. THIS GIVES US THE
CAPABILITY OF TARGETING MORE
SPECIALIZED CHEMICAL SYNTHESIS
BUT ALSO GIVING THE CAPABILITY
TO MORE THAN TWO OR THREE LARGE
CROs TO APPLY TO THIS. I'M A
MEDICINAL CHEMIST, I HAVE BEEN
MY WHOLE CAREER AND THE TWO
FOLKS IN THE POOL NEVER WORKED
WITH BEFORE SO THERE IS A LOT OF
FOLKS OUT THERE I KNOW COULD DO
GOOD SYNTHESIS, WE DIDN'T HAVE
THAT CAPABILITY BECAUSE THEY
HAVE NO BIOLOGY AT ALL, ALL JUST
CHEMISTRY. THIS IS GREAT
OPPORTUNITY TO EXPAND THAT
SCOPE. ONE FINAL POINT TO MAKE
ON THIS SLIDE. WE HAVE ALWAYS
WORKED WITH OUR OFFICE OF
SITUATION FOLKS BECAUSE THEY
HELP US EXPAND WHAT WE DO. THEY
CAME UP WITH A MECHANISM CALLED
ONRAMPING THAT WE ARE GOING TO
TRY WITH THIS NEW INITIATIVES
WHERE WE CAN BRING NEW
CONTRACTORS THAT PROVIDE NEW
CAPABILITIES OR BRING IN NEW
CONTRACTORS TO REPLACE FOLKS
THAT LEAVE SO THAT WE HAVE THE
CAPACITY AT ALL TIMES MAXIMIZE
AS WELL AS THE COMPETITION.
GREAT IDEA LOOKING FORWARD HOW
THAT CAN HELP AND WHEN WE HAVE A
CYCLE REFRESH THE CONTRACTOR
POOLS REALLY JUST A SPECTACULAR
IDEA. SO I HAVE MET WITH
DOCTORS BOCKENSTEDT AND STEWART
AND THEY WERE SUPPORTIVE OF THIS
PROGRAM, THE GAP FILLING MODEL
SPLITTING TO TWO CONCEPTS MADE
LONGCAL SENSE, THE PROGRAM IS
PRACTICAL AND ESSENTIAL TO
DEVELOPING AND DELIVERING
PRODUCTS.
. THEY SUPPORTED THE IDEA
ALLOWING MORE SPECIALIZED AND
SMALLER ORGANIZATIONS TO SUPPORT
SPECIALIZED AREAS AND INCREASE
COMPETITION, THEY DID
ACKNOWLEDGE THE VOLUME OF PCS
ACCOMPLISHMENTS SINCE THE PAST
MID -- AND ALSO DISCUSS SECTORS
WE DISCUSS SECTORS THAT USE
SERVICES WHICH DR. HEWITT
PROVIDED FOR THIS WHOLE GROUP.
AND A SUGGESTION I AGREE WITH,
WE CAN INCREASE AWARENESS OF THE
PROGRAM TO THE SCIENCE
COMMUNITY. WE HAVE A PRETTY
SOLID APPROACH HOW WE DO
OUTREACH BUT ALWAYS BETTER WAYS
TO DO IT. I APPRECIATE THAT
FEEDBACK. ANY QUESTIONS YOU HAVE
AT THIS TIME?
>>ANY QUESTIONS FROM COUNCIL
MEMBERS ONLINE OR IN THE ROOM?
THIS PROPOSAL?
>>REALLY SUPPORTIVE OF THIS
PROGRAM. IT HAS BEEN SHOWN HOW
PRODUCTIVE IT IS, IT IS ADJUSTED
TO THE CHANGING ENVIRONMENT,
SPLITTING IT INTO TWO MAKES
TOTAL SENSE. REITERATE MY
SUPPORT.
>>I CAN ECHO THAT AS WELL. THIS
IS DR. BOCKENSTEDT. WE CAN'T SEE
YOUR FACE BECAUSE THE SLIDES,
THERE WE GO. THANK YOU. I'M
VERY SUPPORTIVE OF THIS, ALL THE
REASONS LISTED THERE, I THINK
THAT GETTING MORE AWARENESS TO
THE SCIENTIFIC COMMUNITY OUT
THERE, EVEN PEOPLE WHO TEND TO
FINE THINGS THEY -- FIND THE
THINGS THEY NEED WHEN THEY NEED
THEM AND NOT SOMETHING THAT
SOMETHING THEY PLAN FOR
NECESSARILY ALONG -- IN ADVANCE
SO VERY IMPORTANT TO CONTINUE
THIS.
>>OUR SECOND CONCEPT CONTINUING
ON PRE-CLINICAL SERVICES THEME
DR. LARRY WOLFRAIM WILL PREVENT
TESTING AND OTHER VACCINES AND
OTHER BIOLOGICS FOR INFECTIOUS
DISEASE.
>>GOOD AFTERNOON, EVERYONE. I'M
DR. LARRY WOLFRAIM, CHIEF OF
BIODEFENSE VACCINES AND OTHER
BIOLOGICAL PRODUCTS DEVELOPMENT
SECTION. THAT'S THE FIRST
ACRONYM. OFFICE OF BIODEFENSE
RESEARCHERS AND TRANSLATIONAL
RESEARCH. SO NOW WE ARE DONE
WITH ACRONYMS WITH DMID. NOW I
WILL PRESENT ON CONCEPT
EVALUATION AND TESTING SERVICES
FOR VACCINES AND BUY LOGICS,
MORE LIKELY TO REFER TO AS THE
VACCINE TESTING CONTRACT FOR
SIMPLICITY. I'M DRIVING THE
BUS. SO THE OBJECTIVE IS TO
PROVIDE A SUITE OF PRE-CLINICAL
NON-CLINICAL AND CLINICAL
SERVICES AND ASSAYS, VACCINES
AND OTHER BIOLOGIC PRODUCTS.
THIS IS A RENEWAL. THE MECHANISM
IS AN IDIQ. ANTICIPATED NUMBER
OF AWARDS BETWEEN ONE AND FIVE
FOR EACH TASK AREA. THIS SLIDE
SPEAKS TO IMPORTANCE OF
SCIENTIFIC NEED. A LOT OF THIS
MY COLLEAGUE DR. HEWITT WENT
OVER IN HER TALK. THESE ARE GAP
FILLING SERVICES, BASICALLY ONE
OFFS, IF YOU WILL. TO PROVIDE
CRITICAL SERVICES TO FILL GAPS
FOR MEDICAL COUNTER MEASURES IN
THIS CASE, THE VACCINES OR OTHER
BIOLOGICS TO PROGRESS ALONG THE
PATHWAY TO WHAT EVENTUAL
LICENSURE. THAT'S IN CONTRAST TO
OUR PD OR PRODUCT DEVELOPMENT
CONTRACT AND VAAs WHICH IS DR.
HEWITT EXPLAINED ARE DIFFERENT
THEY ENCOMPASS EVERYTHING THEY
NEED TO ADVANCE VACCINE
CANDIDATE FROM PROOF OF CONCEPT,
PRE-CLINICAL DATA THROUGH TO
INITIATION, COMPLETION OF PHASE
1 TRIAL. THESE ARE GAP FILLING
IN CONTRAST. WHAT WE CAN DO WITH
VACCINE TESTING PRE-CLINICAL
SERVICES CONTRACT IS TO PROVIDE
NON-CLINICAL EFFICACY AND
IMMUNOGEN AT THISTY DATA TO
SUPPORT CLINICAL GO NO GO
DECISIONS, ON THE PART OF THE
PRODUCT DEVELOPERS. HELP DEFINE
OR REFINE PRODUCT FORMULATIONS
INCLUDING DOSE AND SCHEDULE.
VERY POPULAR TASK AREA HERE IS
TALKS OR SAFETY STUDIES,
TYPICALLY GLP IND ENABLING
STUDIES. GOING TO ALSO PROVIDE
OTHER GAPS TO FILL IND PACKAGES.
WE CAN DEVELOP CRITICAL ASSAYS
AND INTERNATIONAL STANDARDS WE
ARE DOING MORE RECENTLY, FOR
EXAMPLE WITH THE INTERNATIONAL
STANDARDS WE ARE WORKING IN
COLLABORATION WITH (INAUDIBLE)
TO DEVELOP WHO ANTIBODY
INTERNATIONAL STANDARDS FOR
MARCHBURG AND SUDAN. THESE
SERVICES CAN BE RAPIDLY DEPLOYED
TO SUPPORT OUTBREAK AND PANDEMIC
RESPONSE, RECENT EXAMPLE IS FOR
THE COVID-19 PANDEMIC, WE WERE
ABLE TO SET IN PLACE QUICKLY
TASK ORDERS TO DEVELOP CRITICAL
IMMUNE ASSAYS BUT DEVELOP THE
ASSAYS QUALIFY AND VALIDATE AND
ULTIMATELY TEST CLINICAL TRIALS
STAFF AND THAT WAS UNDER
AUSPICES OF THE US GOVERNMENT
WIDE RESPONSE THAT WAS THEN
KNOWN AS OPERATION WARP SPEED.
OVERALL WE ARE DERISKING
CANDIDATES TO SUPPORT FURTHER
ADVANCE DEVELOPMENT AND/OR
FUNDING SO FUNDING COULD BE
OTHER US GOVERNMENT AGENCIES,
OVER TRANSITION PARTNERS LIKE
BARTA. ALSO NON-PROFITS LIKE THE
BILL AND MELINDA GATES
FOUNDATION OR SEPE OR POSITION
THESE PROGRAMS FOR PRIVATE
EQUITY FUNDING. THE TYPE OF
QUESTIONS WE GET SPAN IT IS
GAMUT INDUSTRY, SMALL BIOTECH,
ACADEMIC INVESTIGATORS OR US
GOVERNMENT. THIS IS A HISTORY,
THIS IS A RECOMPETE. PREVIOUSLY
THERE WERE TWO AWARDS, THESE
WERE SINGLE AWARDS MADE TO THE
SAME ORGANIZATION, SO THE FIRST
CONTRACT RAN FROM 2012 THROUGH
2018. CURRENTLY ACTIVE CONTRACT
WAS AWARDED TO PATEL IN 2018.
FOR BOTH OF THESE THERE WERE
FIVE TASK AREAS VERSUS
ADMINISTRATIVE WHICH SUPPORTS
CONCEPT DEVELOPMENT PLANS,
INFORMATION REPORTS, SITE VISITS
OR AUDITS,S THE SECOND IS ASSAY
DEVELOPMENT FOR NON-CLINICAL AND
CLINICAL TESTINGING. THE THIRD S
NON-CLINICAL IMMUNOGENICITY AND
EFFICACY TESTING AND APPROPRIATE
ANIMAL MODELS SPANNING BSL 2 ALL
THE WAY TO BSL 4. NON-CLINICAL
AND CLINICAL SAMPLE TESTING THEN
FINALLY SAFETY AND TOXICITY
TESTING. THIS SLIDE IS
SUMMARIZING, I WILL START ON THE
RIGHT HERE THE PIE CHART. SO
THIS IS SHOWING THE RELATIVE
REPORTS OF INDIVIDUAL TASK
ORDERS BY PATHOGEN WITH TWO
EXCEPTIONS WHICH I WILL MENTION
IN A MINUTE. INTERESTING WE DID
A LOT OF WORK ON THE RECENT
CONTRACT FOR SARS COV-2
INFLUENZA, FETAL VIRUSES, THEN
THE TWO WHICH ARE PATHOGEN
AGNOSTIC ARE BSL IV AND
TOXICOLOGY. EACH OF THESE ARE
SINGLE STANDING TASK ORDERS
UNDER WHICH WE CAN DO STUDIES
FOR ANY PATHOGEN BSL 4 PATHOGEN,
THE BSL 4 TOX STUDY, WHICH AM
COME DATES VACCINE CANDIDATES
FOR ANY PATHOGEN. IN TERMS OF
HOW WE ACCOMPLISH, WHAT I FOCUS
ON HERE ARE WAYS IN MANY WHICH
THE PRE-CLINICAL SERVICES FOR
VACCINE TESTING CONTRIBUTED TO
VACCINE CANDIDATES THAT HAVE
ULTIMATELY BEEN LICENSED. THE
TOP HERE BIOTHORAX, EMERGENT ADA
POST EXPOSURE PROPHYLAXIS
VACCINE, SECOND EXAMPLE GOING TO
A LITTLE MORE DETAIL IS JANSEN
26 MVA EBOLA VACCINE, WE
PROVIDED A LOT IN TERMS OF
CONTRIBUTION FOR PRE-CLINICAL
SERVICES, MOST IMPORTANT OF
WHICH IS THE WHOLE IDEA OF
TESTING, THE I 26 TOGETHER WITH
THE NVA. THAT WAS DONE UNDER
PRE-CLINICAL SERVICES. SO JUST
TO GIVE A LITTLE BACKGROUND
THERE WERE TWO PRODUCT
DEVELOPMENT CONTRACTS UNDER VAA,
ONE TO JANSEN THE I 26 VECTOR
EBOLA VACCINE. THE OTHER
CONTRACT WAS AWARDED TO
(INAUDIBLE) THE MVA BASED
VACCINE CANDIDATE. NEITHER ONE
ALONE WAS SHOWING PROMISING
EFFICACY, NON-HUMAN PRIMATE
CHALLENGE MODEL WITH THE EBOLA.
LOOKING AT THE LITERATURE THE
(INAUDIBLE) AT THAT TIME ON
THESE TWO CONTRACTS, SAW SET A
PRECEDENT FOR COMBINING THESE
TWO IN THE PRIME BOOST. WE
COULDN'T DO THAT, COULDN'T TEST
EFFICACY OF THE HETEROLOGOUS
PRIME BOOST UNDER THE BAA
CONTRACTS BECAUSE THE SCOPE OF
THOSE CONTRACTS IS LIMITED TO
VACCINE CANDIDATES THAT WERE IN
THE ORIGINAL PROPOSALS. SO THE
VACCINE TESTING SERVICES PROVIDE
MECHANISM WHEREBY WE CAN GET OUT
OF THE PROOF OF CONCEPT DATA AND
TURNED OUT SUCCESSFUL ULTIMATELY
JANSEN LICENSED THE NORDIC MVA
PA PART OF THE COMB POINT AND
PRIME BOOST REGIMEN VACCINE WAS
APPROVED IN EUROPE IN 2020. THE
NEXT EXAMPLE IS THE QUADRIVALENT
DENGE VACCINE, LICENSED IN
SEVERAL TERRITORIES NOW,
PRE-CLINICAL SERVICES PROVIDE
SUPPORT OF THAT PROGRAM. THEN
MOST RECENT EXAMPLE WAS THE NEXT
GENERATION ANTHRAX VACCINE. THIS
IS EMERGENT VIRAL SOLUTIONS,
BASICALLY THE FIRST ANTHRAX
VACCINE T FIRST BULLET ADA WITH
A SECOND ADJUVANT SETTING CPG
709. WHICH WAS APPROVED BY FDA
IN JULY OF THIS YEAR. THIS SLIDE
IS ADDRESSING THE OUTBREAK
RESPONSES TO OUTBREAKS AND
THREATS HOW PRE-CLINICAL
SERVICES THE VACCINE TESTING
CONTRACT SPECIFICALLY HAS MADE A
DIFFERENCE. SO FOR EBOLA I
TALKED ABOUT THE HETEROLOGOUS
PRIME BOOST AND A MECHANISM TO
DO THAT. WHAT THIS IS FOCUSING
ON, THIS IS THE PAPER IN THE
UPPER LEFT PUBLICATION
DESCRIBING THE CRITICAL
NON-HUMAN PRIMATE IMMUNOGENICITY
EFFICACY DATA GENERATED ON A
NUMBER OF TASK ORDERS WHICH WAS
USED FOR THEIR JANSEN
IMMUNOBRIDGING PACKAGE, VERY
INSTRUMENTAL GETTING THIS
VACCINE CANDIDATE LICENSED IN
THE EU. THE UPPER RIGHT IS
EXAMPLE FROM ZIKA. WE HAD A TASK
ORDER WHICH DEVELOPED AND
OPTIMIZED QUALIFIED ET CETERA,
NUMBER OF CLINICAL ASSAYS,
IMMUNE ASSAYS FOR ZIKA USED TO
TEST CLINICAL TRIALS SAMPLES
FROM A NUMBER OF PHASE 1
CLINICAL TRIALS. THE BOTTOM LEFT
IS SARS COV-2. HERE WHAT WAS
DONE, AGAIN LOT DONE UNDER
AUSPICES OF OPERATION WARP
SPEED. THIS PARTICULAR
PUBLICATION HERE, THE DATA IS
COMING FROM A LIVE VIRUS
MICRONEUTRALIZATION ASSAY, IT
WAS THE FIRST OF ITS KIND, THE
FIRST LIVE VIRUS MUTUALIZATION
ASSAY TO BE VALIDATED. IT WAS
USED TO TEST SAMPLES FROM THE
MODERNA PHASE 3 CLINICAL TRIALS,
THE DATA WAS USED IN BLA
SUBMISSION AS WELL AS ANALYSES
OF CORRELATES OF PROTECTION.
BOTTOM RIGHT IS INFLUENZA. WE
DID TOX AND CLINICAL ASSAY
STUDIES AS WELL AS DEVELOPMENT
OF IMMUNE ASSAYS TO SUPPORT THE
CLINICAL TRIALS. IN THE MIDDLE
IS MPOX. HERE, WE TOOK AN ASSAY
THAT HAD ORIGINALLY BEEN USED TO
ASSESS NEUTRALIZING ANTIBODY
LEVELS TO VAX SINIA. THAT WAS
THE PLAQUE REDUCTION
NEUTRALIZATION TEST AND
OPTIMIZED FOR TESTING FOR
NEUTRALIZING ANTIBODY TITERS
MPOX AND THE ASSAY THAT WAS
OPTIMIZED THEN USED TO TEST
CLINICAL TRIALS FROM NIAID
SPONSORED PHASE 2 DOSE BARING
CLINICAL TRIAL USING THE
LICENSED (INDISCERNIBLE)
VACCINE. THIS SUMMARIZES THE
CHANGES WE ARE ENVISIONING FOR
2025, I MENTIONED EARLIER THE
FIRST ITERATIONS OF THIS
CONTRACT, 2012 AND CURRENTLY
2018 ARE SINGLE AWARDS TO THE
SAME OFFER, WHAT WE ARE
ANTICIPATING THIS YEAR, PLANNING
TO DO IS MAKE MULTIPLE AWARDS.
THE SINGLE AWARD IDEA TENDS TO
BE THE EXCEPTION. THIS CONTRACT
NOW MAYBE THE ONLY ONE WHICH IS
A SINGLE AWARD. THERE ARE LOT OF
ADVANTAGES FOR MULTIPLE AWARDS
COMPARED TO A SINGLE, SOME OF
THESE ARE MORE OBVIOUS THAN
OTHERS SO GREATER COMPETITION.
THE ABILITY TO PERHAPS DRIVE
DOWN COSTS, ACCESS NEWER
CAPABILITIES AND PERHAPS EVEN
BRING ON BOARD SMALL BUSINESS,
SMALL BUSINESSES WHICH IS
ANOTHER MANDATE. ONE PROBLEM WE
ARE RUNNING INTO NOW IS THAT
WITH THE INCUMBENT, IF WE WANT
TO DO STUDIES UNDER BSL 4
CONTAINMENT THAT HAS TO BE DONE
THROUGH SUBCONTRACTING BECAUSE
INCUMBENT DOESN'T HAVE THEIR OWN
BSL 4 FACILITIES. THEN MORE
RECENTLY THERE'S BEEN A CHANGE,
WE USED TO BE ABLE TO DO TOX
STUDIES, WITHOUT THE NEED FOR
SUBCONTRACTING BUT THAT IS
RECENTLY CHANGED BECAUSE THE
INCUMBENT HAS SPUN OFF TALKS --
TOX UNIT TO ANOTHER ENTITY SO
THEY HAVE TO DO THAT THROUGH
SUBCONTRACTING WHICH MAKES IT
MORE COMPLICATED AND ADDS
ADDITIONAL LAYERS OF COST. SO
THE MAJOR CHANGE HERE IS
PREVIOUSLY OFFERED TO RESPOND TO
ALL TASK AREAS. FOR THIS
ITERATION WE ALLOW TO APPLY TO
SINGLE TASK AREA OR MULTIPLE. UP
TO THEM. THEY DON'T NEED TO
RESPONSE TO ALL OF THEM NOW. WE
ARE TRYING TO STREAMLINE THE
TASK AREAS 2 AND 4. TWO IS ASSAY
DEVELOPMENT AND 4 IS CLINICAL
NON-CLINICAL SAMPLE TESTING NOW
A SINGLE TASK AREA. WE ARE ALSO
ELIMINATING ADMINISTRATIVE
SUPPORT, A SEPARATE TASK, WE
WANT TO BRING ADMINISTRATIVE
SUPPORT UNDER THE UMBRELLA OF
EACH AWARDED TASK ORDER. SOME
OF THE FEEDBACK THAT I GOT, SOME
GRATEFUL TO PROFESSORS GREENBERG
ANDs THESE FOR THEIR COMMENTS.
-- ESTES FOR THEIR COMMENTS. ONE
COMMENT NOTE -- ONE COUNCIL
MEMBER NOTED GOING FROM SINGLE
AWARD TO MULTIPLE AWARD WOULD BE
MORE COMPLICATED TO MANAGE. THAT
IS TRUE, THERE WILL BE MORE
EFFORT ON THE PART OF THE
PROGRAM STAFF TO REVIEW THESE
PROPOSALS BECAUSE INSTEAD OF A
SINGLE PROPOSAL THERE COULD BE
MULTIPLE. IT MAY TAKE A LITTLE
LONGER TO ISSUE TASK ORDER
AWARDS AS A RESULT. HOWEVER THE
ADVANTAGE I ALLUDED TO EARLIER
THE INCREASE COMPETITION PERHAPS
GETTING A BETTER PRICE REDUCING
THE NEED TO SUBCONTRACT, THOSE
ALL OFFSET THE ADDITIONAL
COMPLEXITY WHEN IT COMES TO OUR
END TO MANAGE THES THESE. THE GS
ALWAYS TO SELECT THE
BEST-IN-CLASS CONTRACTORS FOR
EACH TASK AREA. THEN AFTER THE
POOLS ARE CREATED, WE ARE ALSO
GOING TO USE THE SAME STRATEGY
TO SELECT THE BEST WHEN WE GET
PROPOSALS FROM CONTRACTORS WHEN
WE ISSUE NEW VISUAL TASK ORDERS.
THERE IS ALSO A QUESTION I THINK
WHAT MY COLLEAGUE DR. HEWITT
ADDRESSED THIS VERY WELL BUT
HAPPY TO ANSWER ADDITIONAL
QUESTIONS, IT WAS DURING THE
PRESENTATION ON EARLIER SLIDE I
MENTION WE SUPPORTED VACCINE
TESTING CONTRACT MORE THAN 75
VACCINES OR BIOLOGIC CANDIDATES
BUT OF COURSE THE ENTIRE
UNIVERSE OF VACCINE AND
BIOLOGICS LARGER THAN 75. HOW TO
NARROW IT DOWN TO SUPPORT 75. I
THINK THAT WAS ADEQUATELY
ADDRESS THROUGH DETAILED SLIDE
DECK DR. HEWITT WENT THROUGH,
YOU CAN ADD ANYTHING TO THAT IF
YOU WOULD LIKE. THAT BRINGS ME
TO THE END OF MY PRESENTATION.
THANK YOU, VERY MUCH FOR YOUR
TIME AND ATTENTION. I WOULD BE
HAPPY TO ANSWER ANY QUESTIONS
THAT YOU MIGHT HAVE. DR.
GREENBERG.
>>THANK YOU VERY MUCH. THAT WAS
VERY INFORMATIVE. WONDERING IN
GENERAL I CAN THINK OF A LOT OF
TYPES OF USERS OF THIS SERVICE
INDUSTRY, ACADEMIA AND THE
INTRAMURAL PROGRAM (INAUDIBLE)
COMES TO MIND. DO YOU THINK IT
IS SORT OF A LITTLE BIT OF EACH?
OR IS ONE GROUP MUCH MORE
REPRESENT -- I WONDER WHO IS
USING IT?
>>I WOULD SAY WE ALL THREE YOU
REFERENCE ARE REPRESENTED AS
TRUE. I WOULD SAY -- I THINK THE
BULK IS COMING FROM SOFT
COMPANIES AND ACADEMIC
INVESTIGATORS. THAT IS MY
RECOLLECTION.
>>THANKS.
>>NICE PREGNANT. GREAT YOU
PIVOT WITH YOUR EXPERIENCE TO
BREAK THIS UP. I HOPE YOU DO
HAVE THE EXTRA COMPETITION THAT
COMES IN WITH THIS. I THINK IT
IS A GOOD PROGRAM, CERTAINLY
VERY SUPPORTIVE OF CONTINUING TO
SUPPORT THIS.
>>THANK YOU.
>>GO AHEAD.
>>KEN, YOU GO FIRST I WILL GO
RIGHT AFTER.
>>JUST WONDERING THE PREVIOUS
AWARD WERE THERE SUBCONTRACTS
FROM THAT SINGLE AWARD? AND WILL
BE POTENTIAL SUBCONTRACTS FROM
THESE INDIVIDUAL AWARDS ALSO?
>>THERE CERTAINLY WERE
INSTANCES -- RIGHT. SO THE
AWARDS WERE MADE -- THE INITIAL
AWARDS MADE TO THAT PRIME
CONTRACTOR INCUMBENT IN THIS
CASE PATEL. WHEN INDIVIDUAL
REQUEST FOR TASK ORDERS ARE
MADE, IT IS UP TO THE CONTRACTOR
TO DECIDE WHETHER OR NOT THEY
CAN DONNA HOUSE OR NEED TO
SUBCONTRACT. THERE'S CLEAR
EXAMPLES TO SUBCONTRACT. A
COUPLE I CITED WERE STUDIES THAT
NEED TO BE DONE UNDER BSL 4
CONTAINMENT SO THEY DON'T HAVE
THAT CAPABILITY AS NECESSITY,
THEY HAVE TO SUBCONTRACT.
PARTWAY THROUGH THE CURRENT
CONTRACT THEY LOST THEIR ABILITY
TO DO TOXICOLOGY STUDIES. THAT
IS A VERY POPULAR SERVICE WE
PROVIDE. SO NOW -- SO THEY SPUN
OFF A FOR PROFIT ENTITY
AMPLIFIED BIO, TOX STUDY BUS TO
ACCESS BIO IT IS A
SUBCONTRACTING MECHANISM. TO
ACCESS ANY OTHER CHARLES RIVER
OR ANY OTHER COMPANIES KNOWN FOR
TOX STUDIES WILL HAVE TO BE DONE
LIEU CURRENT CONTRACT TO
SUBCONTRACT TO PATEL. ADDING
COMPLEXITY, TIME, COST, SO
HOPING THAT WILL HAVE SOME
RESPONSES FROM ORGANIZATIONS
THAT CAN DO THE WORK THEMSELVES
AND THERE WILL BE A REDUCED NEED
TO SUBCONTRACT. DR. PALMER.
RELATED TO THAT, WHEN AN
ORGANIZATION APPLIES DO THEY
APPLY FOR THE DIFFERENT PARTS
INDIVIDUALLY OR Z A PACKAGE? THE
REASON I ASK IS OBVIOUSLY THEIR
COST STRUCTURE MATTERS IF YOU
BREAK THAT UP. CURIOUS ON THE
STRATEGY ON THAT.
>>THAT IS UP TO THE OFFER. IF
THERE IS ONLY ONE TASK AREA,
WHERE THEY CAN BE RESPONSIVE TO
THEY CAN RESPOND TO THAT SINGLE
ONE. IF THEIR PROPOSAL LOOKS
GOOD, FROM A COST PERSPECTIVE
THE THEY WILL BE PART OF THAT
POOL. THEY CAN APPLY TO MULTIPLE
SO THEY WILL BE PART OF MULTIPLE
POOLS. ASSUMING THE PROPOSALS
PASS MUSTER. THEN WE SEND
REQUEST FOR TASK ORDER
PROPOSALS, THOSE WILL GO OUT TO
THE CONTRACTORS IN THOSE
INDIVIDUAL POOLS.
>>THANK YOU.
>>SORT OF LIKE SETTING UP A
CONSORTIUM EACH OF THESE
CONTRACTOR POOLS IS LIKE A
CONSORTIUM UNDER THE PARENT
CONTRACT OR AS DR. HEWITT
REFERRED TO IT AS A FISHING
LICENLICENSE. NO GUARANTEE YOU L
CATCH ANYTHING BUT AT LEAST YOU
HAVE THE POSSIBILITY OF CATCHING
SOMETHING.
>>THAT IS WHY THEY CALL IT
FISHING AND NOT CATCHING.
>>THAT'S RIGHT. YES.
>>THANK YOU, LARRY.
>>THANK YOU.
>>MOVING ON OUR NEXT PRESENTER
IS DR. DAN STOUGHTON FROM THE
SAME SECTION, SAME OFFICE WITHIN
DMID.
>>THANK YOU FOR LETTING ME
PRESENT VACCINE AND OTHER
BIOLOGICS MANUFACTURING
CHARACTER SIXTH SERVICES. TAKE A
MOMENT TO COMMENT ON HOW WHAT
I'M GOING TO PRESENT IS VERY
SIMILAR TO WHAT YOU HEARD FROM
OTHER SERVICES, AND HOW
PRE-CLINICAL SERVICES INTERACT
TOGETHER WE LEARN FROM EACH
OTHER HOW TO DO CONTRACTING
TOGETHER AND WE DO SERVICES PART
TOGETHER TOO. WE ARE A VERY
INTEGRATED ORGANIZATION. THE
OBJECTIVE PROVIDE A SUITE OF
MANUFACTURING SERVICES TO
SUPPORT MANUFACTURE OF
PRE-CLINICAL STUDIES AND ALSO
CLINICAL TRIAL MATERIAL.
FOCUSING ON PHASE 1 AND 2,
BECAUSE WE ARE LOOK AT DIFFERENT
CONCEPTS GOING INTO CLINIC AND
EXTENSIVE COST INCREASE WHEN YOU
GO TO MARKET PRODUCTS. THIS IS A
RENEWAL. IF APPROVED THIRD TIME
THROUGH LIKE LARRY SAID WE DID
THIS IN 2012, 2018 AND HOPEFULLY
2025. MECHANISM IS IDIQ HOWEVER
WE HAD CONTRACTORS THAT OFFER
OTHER FUND MECHANISMS AND WE ARE
OPEN AS NEEDED AS
PRO-APPROPRIATE. ANTICIPATED
NUMBER OF AWARDS ONE TO THREE
FOR EACH AREA. I WILL DISCUSS
THAT AND YOU WILL SEE A
RECURRING THEM AND CONTENT WE
PROVIDE AS SERVICE DOESN'T
CHANGE BUT HOW WE MAKE IT MORE
RIGHT SIZE TO MAKE IT CHANGE. SO
THE PRODUCTS WE SUPPORT ARE
VACCINES OTHER BIOLOGICS,
CHALLENGE MATERIAL FOR HUMAN
CHALLENGE STUDIES AND
PRE-CLINICAL STUDIES AND
ASSOCIATED VACCINE COMPONENTS,
ADJUVANTS CRITICAL REAGENTS,
ASSAY AGENT CELL BANKS.
PREDOMINANTLY BSL 2 BUT
CAPABILITY OF 3 AND 4 WHICH IS A
LITTLE UNUSUAL. THE SERVICES
STARTS WITH PRODUCT DEVELOPMENT
PLANS. THIS IS ONE OF THE FEW
PLACES WE ALLOW SOMEBODY WHO
DOESN'T KNOW WHAT THEY WANT TO
COME IN AND FIGURE OUT, HELP
CREATE A DRAFT PLAN TO TAKE A
NOVEL CANDIDATE FROM PROOF OF
CONCEPT THROUGH DEVELOPMENT
MANUFACTURING PRE-IND
TOXICOLOGY, AND WE CAN SHEPHERD
HOW TO DO THAT AND HELPS THEM
FIGURE WHAT THEY NEED TO DO AND
HOW THEY NEED TO DO IT. SO THIS
IS ONE OF THE SERVICES WE LIKE
TO KEEP IN BUT IT IS A PAPER
EXERCISE. SO WE FOUND THAT AS A
PAPER EXERCISE IT DOESN'T FIT
WITH WHAT A CMO DOES. CMOs DO
AUTHORIZATION, PROCESS
DEVELOPMENT, MANUFACTURING PROOF
REAGENTS, MANUFACTURING CLINICAL
TRIAL MATERIAL. MOVING ON TO
WHAT JUDY WAS TALKING ABOUT, WE
TEND TO GET TWO DIFFERENT
CLASSES OF PRODUCT TO DERISK
SOME THINGS. WE HAVE PRODUCT
SWITCH COME IN, WE DON'T
RECOMMEND SCALABLE, WE DON'T
KNOW IF WE CAN MAKE IT IN THE
GMP COMPLIANT MANNER. WE DON'T
THINK IT WILL PASS A STUDY
SECTION. SO THIS IS JUST TOO
RISKY. SO I PUT IN A YEAR'S
WORTH OF RESOURCES IN IT WE CAN
IDENTIFY WHETHER OR NOT WE CAN
MANUFACTURE THE PRODUCT THEN
CREATE VALUE TO PEOPLE COMING
BACK TRY FOG GET A VAA OR OTHER
CONTRACT OR FUNDING SUPPORT.
ONE WE DIDN'T TALK ABOUT SO MUCH
IS WHEN WE DO THIS EARLY WORK,
IT IS VERY IMPORTANT THE
CONTRACT MANUFACTURING
ORGANIZATIONS DO NOT TAKE ANY
IP. SO ALL PRE-CLINICAL SERVICES
HAVE A DETERMINATION OF
EXCEPTIONAL CIRCUMSTANCE WHICH
MEANS THE CMOs ACT AS FIRST
FEE FOR SERVICE CONTRACT
ORGANIZATION AND ALL PROPRIETARY
INFORMATION AND ALL INDIVIDUAL
-- INTELLECTUAL PROPERTY FLOWS
BACK TO GOVERNMENT AND BACK TO
THE PRODUCT YOU KNOW
INVESTIGATOR. -- INNOVATOR. SO
DO NOT LOSE ANY OF THEIR
PROPRIETARY INFORMATION OR HAVE
SOMEBODY ELSE TAKE A PIECE OF
THE PIE. THE OTHER TYPE OF
PROJECT WE GET ARE FILL IN THE
GAPS. SOMEBODY HAS A BA
CONTRACT AND THEY NEED A MASTER
CELL BANK, SOMEBODY DISCOVERED
THE PRODUCT ISN'T STABLE, THEY
NEED FORMULATION STUDIES THAT
DOESN'T FIT THE SCOPE OR FUNDING
WHAT THEY ARE DOING AND ABLE TO
PROVIDE THAT AS WELL. SO KEY
ACCOMPLISHMENTS IN 2018 SHOWN
HERE WE HAVE DONE FIVE PRODUCT
DEVELOPMENT PLANS PROCESS
DEVELOPMENT PROJECTS,
MANUFACTURE TWO CLINICAL TRIAL
MATERIALS, TALK ABOUT THAT IN A
MINUTE. WE HAVE HAD A LOT OF
MASTER BANK REQUESTS, AND
SPEAKING TO WHAT LARRY SAID
EARLIER, THE TOX STUDIES PRODUCT
DEVELOPERS OUTSOURCE MASTER
BANKS ANYWAY SO A POPULAR
SERVICE TO REQUEST. BECAUSE IT
IS A POPULAR SERVICE WE RETHINK
HOW TO PROVIDE THAT TO THE
GREATER COMMUNITY. ENHANCING
FORMULATION STUDIES IN 2017,
2016, FIVE MIXING STUDIES.
CURRENTLY WE DON'T HAVE ANY.
THAT IS SOMETHING WE MAY COME UP
AND HAVE IN THE FUTURE.
STABILITY STUDIES ALSO FAIRLY
COMMON THING TO REQUEST TO
EXTEND STABILITY STUDIES FOR
PRODUCT WHICH THE CONTRACT IS
LANGUAGE. WHAT ARE THE SPECIFIC
ACCOMPLISHMENTS? WITH THE
PRODUCT DEVELOPMENT PLANS, WE
HAVE DONE PDPs FOR PRODUCT
PANS FOR INFLUENZA,
TUBERCULOSIS, COMMON -- MRRS,
LANDSCAPE ANALYSIS FOR MERS. WE
HAVE DONE PROCESS FOR DIFFERENT
VACCINE CANDIDATES MICROBIAL
RECOMBINANT PROTEIN CANDIDATES
AND VIRAL CANDIDATES. YOU CAN
SEE WITH THE MASTER BANKS WE
HAVE DONE A LOT OF MASTER BANK
WORK. SPANNING MAMMALIAN AND
SPANNING VIRAL AND MAMMALIAN
CELL LIVE DERIVED, TAKE A MOMENT
TO IDENTIFY OR FOCUS ON THE FIVE
STAPH AUREUS PROJECT WHERE ALL
FIVE WENT TO A PENALTY VALENT
VACCINE CANDIDATE FOR CARBX
CONTRACT CANDIDATE SIMILAR TO
JUDY TALKED ABOUT AND HUMANIZED
CK CELL LINE THAT SUPPORTS
MANUFACTURE OF FLU VACCINE
CANDIDATES. AS SHOWN HERE WE
ALSO DID CLINICAL TRIAL MATERIAL
WITH INACTIVATED WEST NILE VIRUS
OCCURRING NOW, KNOCK ON WOOD,
HOPEFULLY WE WILL BE SUCCESSFUL.
MANUFACTURING H 3N 2 INFLUENZA
VIRUS OR HUMAN CHALLENGE
MATERIAL GONE INTO A DOSE
RANGING CLINICAL TRIAL AND WE
ARE HOPING THAT DATA WILL COME
OUT IN ABOUT SIX MONTHS. SO
WHAT HAVE WE LEARNED? ONE OF THE
DIFFICULTIES WITH THE VACCINES
AND OTHER BIOLOGICS IS PLATFORMS
ARE BROADER AND MORE
CHALLENGING. WE HAVE VIRAL
VACCINES, WE HAVE (INAUDIBLE)
BASED PRODUCTS MICROBIAL BASED
PRODUCTS YEAST BASED PRODUCTS.
INSECT BASED PRODUCTS SO WE HAVE
TO HAVE A WIDE VARIETY OF
PLATFORMS FOR VACCINE
IMMUNOGENS. WE ALSO FOUND OUT
THAT AS RICK SAID BEFORE AS
WELL, NOT ALL TASK AREAS ARE
WELL MATCHED TO WHAT THE
CONTRACTING MANUFACTURING
ORGANIZATIONS DO. THE PDP IS ONE
EASIEST EXAMPLE THAT WE NEED TO
FIND A WRITING ORGANIZATION TO
HELP WITH PRODUCT DEVELOPMENT
PLANS AS OPPOSED TO CONTRACT
MANUFACTURING ORGANIZATION. WITH
THE CMO ONLY FOCUSING ON
MANUFACTURING AND QUALITY AND
CMC DOCUMENTS HAVING REALLY NO
EXPERTISE IN TOXICOLOGY,
CLINICAL TRIAL DESIGN AND
INDs. SO WE NEED THE RIGHT
ORGANIZATION TO PROVIDE THE
RIGHT SERVICE. THE OTHER WRINKLE
THAT WE HAVE COMPARED TO SOME OF
THE OTHER PEOPLE YOU HEARD SPEAK
EARLIER IS WE REQUESTED OF THE
REMAINING CHEMISTRY TYPE OF
WORK, THE CONTRACTORS COULD DO
IT ALL. WE CAN DO DEVELOPMENT,
MASTER SEEDS, DO MANUFACTURING
TO SCALE, WE LIMITED THE POOL OF
CONTRACTORS AND WE EXCLUDED
COMPANIES THAT MAKE MASTER VIRAL
SEATS. THERE'S A LOT OF
COMPANIES THAT MAKE MASTER VIRAL
SEATS AT THE 250 VIRAL RANGE, DO
IT ACROSS THE BOARD TIME AND
AGAIN, BUT THEY DON'T DO
CHROMATOGRAPHY, THEY DON'T
SKDs SO WE WANT TO FOCUS THAT
TO DO THAT TYPE OF WORK. SO HOW
DO WE CHANGE THE STRUCTURE? THE
CONTENT ISN'T GOING TO CHANGE.
WE ARE JUST GOING TO RIGHT SIZE
HOW WE ARE DOING IT. THE -- WE
TRADITIONALLY HAD ADMIN AND
TECHNICAL MANAGEMENT TASK AREA,
DISAPPEARING AS A STAND ALONE
TASK, INCLUDED TO EVERY OTHER
CONTRACT WE HAVE. THE PRODUCT
DEVELOPMENT PLANS EXTRACTED FROM
CMOs, CARVE OUT INDIVIDUAL
TASK AREA FOR PDP LANDSCAPE
REPORTS, HOPING TO FIND
DEDICATED REGULATORY AFFAIRS
ORGANIZATIONS, OTHER TYPE OF
ORGANIZATIONS TO PROVIDE THIS
SUPPORT. THE REMAINING CHEMISTRY
WE WILL BREAK INTO THREE
SECTIONS, BASED ON WHAT WE SEE
IN THE PAST AS WELL. SOME CMOs
IN OUR CURRENT POOL DO
ANTIMICROBIAL WORK OUTSOURCE
DEVELOPMENT WORK SO GREAT TO GO
STRAIGHT THROUGH THOSE
ORGANIZATIONS AND NOT A PRIME
CONTRACTOR TO A SUBCONTRACTOR
FOR THE REASONS YOU HER EARLIER
TODAY. PRODUCT OPTIMIZATION,
PROCESS DEVELOPMENT AND NON-GMP
MANUFACTURING IS ONE TASK AREAS
GMP MANUFACTURING IS A SECOND
AND MASTER BANKS WILL BE A THIRD
TASK AREA. THAT IS HOW WE
ENVISION CHANGING WHAT WE
HAVEN'T DEVELOPED IN THE PAST TO
HOW WE DO IT MOVING FORWARD. SO
AGAIN WE GOT RELATIVELY -- WE
HAVE POSITIVE FEEDBACK, THE
SCOPE IS QUITE LARGE, I DON'T
KNOW THAT WE CAN DO IT OTHER
THAN MANAGE THAT SCOPE. QUESTION
WAS ON HOW WE VETTED PROJECTS,
JUDY PROVIDED EXCELLENT
PRESENTATION ON THAT. THERE WAS
A QUESTION HOW DO WE DO FAILURE?
RICK TALKED ABOUT FAILING EARLY,
FAILING CHEAP OPPOSED TO FAILING
LATE. I THOUGHT WE GO THROUGH
THE FAILURES WE HAVE BECAUSE
THEY ARE ALL DIFFERENT. SOME ARE
FAILURES BUT SOME GO BACK TO BE
R&D MAKING NEXT GENERATION
VERSION OF THAT SAME CANDIDATE.
SO WE HAVE A RHINO VIRUS PRODUCT
DEVELOPMENT PLAN TO MAKE A
MULTI-VALENT VACCINE. WE HAD
EXPLAINED TO THE PRODUCT
INNOVATOR THAT 20 TO 50 IS STILL
TOO HIGH SO THEY KNEW THAT BUT
THEY JUST DIDN'T QUITE -- TO
HELP THEM FOCUS, IDENTIFY HOW
THEY COME UP WITH CONSENSUS
SEQUENCES HOW TO COME UP WITH
MORE NARROW SCOPE AND A STEP
WISE FASHION WORK THROUGH TO A
GOOD CANDIDATE. WE HAVE A
PROTEIN VACCINE CANDIDATE
UNUSUAL ON MOLECULAR LEVEL BUT
ALSO DISCOVERED THERE WAS A
LICENSING PROBLEM THAT
INNOVATOR, KNEW ABOUT BUT HASN'T
THOUGHT THROUGH. BY THE TIME YOU
FINISH MAKING PDP THEY
DISCOVERED THEY WERE BLOCKED,
NOT ABLE TO USE THAT LICENSE WAS
GOING TO STOP MOVING FORWARD.
BUT THEY COULD TAKE THE
INFORMATION AND WE DISCUSSED
PRODUCT OPTIMIZATION AND MADE A
NEXT GENERATION CANDIDATE THEY
CAN PATENT AND NOW HAVE COLLIE
FREE AND CLEAR TO DEVELOP THAT
CANDIDATE. THAT IS A AN ITERATE
WIWIWIN. PARVO VIRUS B 19 FAILE,
COULDN'T MANUFACTURE. WE GOT A
PROCESS, TRIED, THOUGHT IT WOULD
WORK, WE HAD MULTIPLE PROBLEMS
WITH THAT PRODUCT AND WE FOUND
OUT THAT THE PROTEIN SUB UNIT
CHOSEN WOULD NEVER BE A SCALABLE
PRODUCT. THAT WAS A FAILURE,
TERMINATED PROJECT. HSV WAS
TERMINATED, MATERIAL WENT INTO A
NHP STUDY WHICH FAILED A
IMMUNOLOGICAL END POINT. FAILED
BUT FAILED FOR LOSS OF EFFICACY.
ADJUVENTS. WE HAVE HAD -- WE
HAVE HAD A REAL PROBLEM TRYING
TO MAKE ADJUVANT, SOME SUCCESS
AND SOME FAILURES. TECHNICALLY
HELPING SUPPORT MANUFACTURING
ADJUVANT SHOULDN'T BE A
DIFFICULT PROBLEM. BUT THE
LICENSING BECOMES VERY
PROBLEMATIC. ON A FEW OCCASIONS
WE HAVE HAD ADJUVANT
MANUFACTURERS ALLOW US TO MAKE
ADJUNCT FOR A SPECIFIC PRODUCT
AND SPECIFIC PRODUCT YOU KNOW
INVESTIGATOR OR EXTERNAL
REQUESTER, NOT AS A SERVICE TO
MULTIPLE PEOPLE. WE HAVE SOME
ADJUVANT MANUFACTURERS THAT
NEVER WORK WITH US, AND ONLY
WORK DIRECTLY WITH THE PRODUCT
INNOVATORS. SO WE HAVE TO COME
UP WITH A WAY OR ACCEPT WHEN IS
THE LICENSING ISSUE THAT GETS IN
THE WAY AND WE CAN'T MOVE
FORWARD. I THINK THAT ROUNDS UP
EVERYTHING I HAD SO PAUSE AND
ASK IF THERE'S QUESTIONS.
>>SO LAST QUESTION I HAVE, I
ACTUALLY TURNED ON THE
MICROPHONE. SAME QUESTION AS
BEFORE. WHO ARE YOUR USERS? ARE
THEY COMPANIES ACADEMIC? NIH, OR
SOME OTHER GROUP? IS THIS OPEN
TO FOREIGN ENTITIES OR ONLY TO
US COMPANIES?
>>GREAT QUESTION. I WOULD SAY
DIFFERENT. VACCINE MANUFACTURING
LARGE PHARMA DOESN'T WANT TO
MAKE PROCESS DEVELOPMENT OTHER
THAN MASTER BANKS OR CRITICAL
REAGENTS SO THEY ARE MUCH LESS
INCLINED TO USE THESE SERVICES.
PRODUCT DEVELOPMENT PLANS WE
DON'T GIVE TO EXSTRAY SEN DA IN
THE EMERGENCY WORLD BECAUSE THEY
KNOW HOW TO DO THE WORK.
ACADEMIC SCIENTISTS AN SMALL
COMPANIES WHO ARE GREAT
INNOVATORS BUT DON'T NECESSARILY
HAVE THE PRODUCT DEVELOPMENT
EXPERTISE. IT HELPS THEM FIND
OUT THEY NEED TO FIND
STAKEHOLDERS TO HELP THEM OUT OR
SHAREHOLDER HELP THEM TO DO THE
WORK. WE HELP SOME
NON-GOVERNMENT ORGANIZATIONS WE
HAVE DONE SOME WORK FOR NIDDK
FOR PROJECT THEY HAD BECAUSE
THEY DIDN'T HAVE THE RESOURCES
AVAILABLE AND WE DID -- WE
MANUFACTURE PRIZE MATERIALS
WHICH AS JUDY SAID HELP SUPPORT
GRANTS WE CAN'T PROVIDE MONEY TO
BUT CAN PROVIDES A RESOURCE TO.
>>THANKS.
>>I THINK DR. PALMER HAS A
QUESTION. HE HAS HIS HANDS
RAISED.
>>REITERATING ONE VERY
SUPPORTIVE OF THIS BUT ALSO THAT
LAST SLIDE I'M GLAD WAS ADDED
BECAUSE WHAT LOOKED LIKE
FAILURES ARE ACTUALLY SUCCESSES
BECAUSE YOU ARE IDENTIFYING
THESE VERY EARLY AND REDIRECTING
OR PUTTING ENERGY WHERE MORE
PRODUCTIVE. SO WE ALWAYS LIKE TO
SEE A SUCCESS WHERE SOMETHING IS
OUT IN A MARKET AND MAKING A
HEALTHCARE DIFFERENCE BUT THE
EARLY FAILURES BY PROVIDING THAT
WHOLE RANGE THAT SUITE OF
SUPPORT ACTIVITIES, I THINK IS
REALLY CRITICALLY IMPORTANT AND
ADDRESSES ONE MAJOR ISSUE THAT
HAPPENS ESPECIALLY WITH ACADEMIA
AND SMALL COMPANIES. GETTING
STARTED IN THIS. GREAT
PRESENTATION. I APPRECIATE THAT
EDITION.
>>OKAY. THANK YOU. THE LAST OF
THE DMID CONCEPTS, WILL BE
PRESENTED BY JUDY HEWITT, YOU
HEARD FROM EARLIER, THIS IS
CONCEPT FOR THE NEXT VERSION OF
CENTERS OF EXCELLENCE FOR
TRANSLATIONAL RESEARCH.
>>I'M PRESENTING THIS ON BEHALF
OF PAULA BRUNET WHO COULDN'T BE
HERE, SHE SENDS REGRETS, SHE HAD
A COLLEGE VISIT THAT WAS
SCHEDULED TODAY. ON BEHALF OF
THE TEAM THAT WORKED ON THIS
CONCEPT AS WELL. THERE WE GO. SO
THE CENTERS OF EXCELLENCE FOR
TRANSLATIONAL RESEARCH OR
CETRs EXPAND PIPELINE OF
MEDICAL COUNTER MEASURES, FOR FY
25 WE PROPOSE TO FOCUS THAT
AGAINST BACTERIA AND FUNGI WITH
KNOWN EMERGING RESISTANCE.
SUPPORTING TRANSLATIONAL
ACTIVITY SO BEYOND DISCOVERY
LIEU PRE-CLINICAL DEVELOPMENT TO
THE PRODUCT DEVELOPMENT PATHWAY.
THIS IS A RENEWAL THAT IN THE
PAST THE CETRs ARE U 19, WE
ARE HAPPY WITH THAT MECHANISM.
WE ARE PROPOSING 4 TO 6 AWARDS
AT 25 MILLION. SO GIVE YOU A
LITTLE BACKGROUNDETR PROGRAM. IN
THE BEGINNING IN 2003 WE AWARDED
THE FIRST REGIONAL CENTERS OF
EXCELLENCE. THESE WERE
BIODEFENSE AWARDS, RIGHT AFTER
9/11. THEY WERE FOCUSED ON
CATEGORY A A. RENEWED AGAIN IN
2009 SO THE REGIONAL CENTERS OF
EXCELLENCE WERE BASED ON THE TEN
REGIONS IN THE US. ONE IN EACH
REGION. BIG AWARDS IN 2009 THE
RENEWAL WAS CATEGORY A THROUGH
C. IN 2014 WE REFOCUSED A
LITTLE BIT, WHEN WE CALLED THEM
CENTERS OF EXCELLENCE FOR
TRANSLATIONAL RESEARCH SO WE
DIDN'T HAVE A STRICT BIODEFENSE
FOCUS THOUGH AGAIN CATEGORY A
THROUGH C AND EMERGING
INFECTIOUS DISEASES WERE SCOPE
OF THESE AWARDS. THESE WERE U
19s, THEY WERE RENEWED AGAIN
IN 2019 CETR 1.0 AND 2.0. THESE
ARE SYNERGISTIC MULTI-PROJECT
AWARDS WHERE INSTITUTION PICKS A
THEME FOR THEIR AWARD. FROM THIS
BROAD SCOPE OF CATEGORY A
THROUGH C EMERGING INFECTIOUS
DISEASES. ONE OF THE
INTERESTING FEATURES THAT WE
LIKE ABOUT THESE AWARDS IS THAT
THEY HAVE A SAC OR SCIENTIFIC
ADVISORY COMMITTEE. SO THAT IS A
GROUP OF INDEPENDENTS OUTSIDE
EXPERTS THAT HAVE PRODUCT
DEVELOPMENT EXPERTISE WHETHER
INDUSTRY OR REGULATORY, SO THEY
CAN REALLY HELP THIS CETR FOCUS
ON PROJECTS MOVING FORWARD AND
GO NO GO DECISIONS. I WOULD LIKE
TO POINT OUT VERY LARGE SCOPE
BROAD SCOPE HERE LARGE NUMBER OF
AWARDS AND A LARGE DOLLAR AMOUNT
AS WELL. HERE ARE KEY
ACCOMPLISHMENTS FOR THE CETRs.
AT THE END OF 2022, THERE WERE
1300 PUBLICATIONS AND 86 PATENTS
SO THIS IS IMPRESSIVE THOUGH ONE
REVIEWERS POINTED OUT THAT IT IS
LIKELY THAT MANY OF THOSE
PUBLICATIONS WERE RELATED TO
COVID-19. WHICH BRINGS ME TO THE
NEXT BULLET, THIS CETRs PLAYED
A SIGNIFICANT ROLE IN OUR
COVID-19 RESPONSE SO THEY
QUICKLY PIVOTD TO TESTING
REMDESIVIR IN VITRO AND SMALL
ANIMAL MODELS AN ENABLED
PRODUCTS TO MOVE QUICKLY
RAPIDLY. WE HAVE PUBLICATIONS
ON THE RIGHT SO THE ONE ON TOP
TALKS ABOUT NEUTRALIZING
ANTIBODIES FOR OMICRON, AGAIN
PART OF RESPONSE EFFORTS SO WE
HAD A NUMBER OF ACCOMPLISHMENTS
RELATED TO PANDEMIC
PREPAREDNESS, DEVELOPING MEDICAL
COUNTER MEASURES SO THIS SECOND
PUBLICATION HERE IS ANTIVIRAL
FOR ALPHA VIRUS. THAT IS MOVING
ALONG NICELY. WE HAVE ALSO
MONOCLONALS AND VACCINES
SUPPORTED FOR SUDAN OUTBREAKS,
MOVE FORWARD FOR BARTA SUPPORT
AS WEL WELL. SO THAT IS THE THID
PUBLICATION HERE. WE HAVE CETR
ON ANTIMICROBIAL RESISTANCE, DID
LARGE NEW DISCOVERY PLATFORMS
IDENTIFICATION OF THERAPEUTIC
TARGETS AND BROAD SPECTRUM
ANTIBACTERIALS AND ANTI-FUNGALS.
IN CETR 3.0 WE FOCUS ON
ANTIMICROBIAL RESISTANCE. SO
THIS SLIDE IS MEANT TO POINT OUT
HOW IT FITS INTO OVERALL
PORTFOLIO, IT WILL BE A SLIGHTLY
SMALLER PROGRAM FEWER AWARDS,
SMALLER DOLLAR AMOUNT, LARGE
PART BECAUSE IT IS A REALLY VERY
FOCUSED PROGRAM. SO THIS NEXT
SLIDE -- SORRY. THIS SLIDE IS ON
THE IMPORTANCE OF FOCUSING ON
ANTIMICROBIAL RESISTANCE.
THERE'S SOME STALINGERRING
STATISTICS HERE -- STAGGERING
STATISTICS HERE, 5 MILLION
DEATHS GLOBALLY IN 2019
ASSOCIATED WITH ANTIMICROBIAL
RESISTANCE. 100 TRILLION IN
ECONOMIC COSTS. THAT IS OVER A
35 YEAR PERIOD BUT STILL A LOT
OF MONEY. THINKING ABOUT THIS
NOT IF BUT WHEN, NOW IS REALLY A
GOOD TIME TO BE FOCUSING ON
ANTIMICROBIAL RESISTANCE AN
RE-EMPHASIZING THIS AREA BECAUSE
AS WAS PRESENTED EARLIER OUR
RESPONSES HERE ARE GOING TO TAKE
TIME TO COME TO FRUITION SO WE
NEED TO FOCUS ON IT. HERE IS
THE SLIDE HOW CETR 3.
0 FITS WITHIN THE RESEARCH
PORTFOLIO SO THE TEAM THAT GOT
TOGETHER TO THINK ABOUT THE CETR
AND WHAT WE WOULD FOCUS ON WHEN
WE WERE DISCUSSING THE RENEWAL,
LOOKED AT ALL THESE VERY LARGE
CENTER TYPE PROGRAMS THAT NIAID
DMID FUNDED OR WILL BE FUNDING.
BEGINNING WITH THE CENTERS OF
EXCELLENCE FOR INFLUENZA
RERESEARCH THAT FOCUSES
OBVIOUSLY ON FLU NATURAL HISTORY
TRANSMISSION PATHOGENESIS, AND
SURVEILLANCE AS WELL. NEXT WE
HAVE THE CREEDS CENTERS FOR
RESEARCH ON EMERGING INFECTIOUS
DISEASESSER MORE BASIC RESEARCH
AND SURVEILLANCE ON EMERGING
INFECTIOUS DISEASE AND
RE-EMERGING DISEASE. I WILL MOVE
TO THE RIGHT HAND SIDE HERE AND
TALK ABOUT THE AVIDS AND REVAMP
BOTH WHICH ARE FOCUSED ON
PANDEMIC PREPAREDNESS EFFORTS SO
THE AVIDS ARE ANTIVIRAL DRUG
DISCOVERY CENTERS SPECIFICALLY
LOOKING FOR DIRECT ACTING
ANTIVIRALS AGAINST THE SEVEN
VIRAL FAMILIES OF PANDEMIC
POTENTIAL. THE REVAMPS ARE BEING
REVIEWED NOW, THOSE ARE FOCUSING
ON VACCINE MONOCLONAL DISCOVERY
AND DEVELOPMENT CENTERS, FOR THE
SAME FAMILIES OF VIRUSES. MOVING
BACK TO THE LEFT INTO BACTERIA
HERE, WE HAVE THE IMPACT TB, THE
IMMUNE MECHANISMS OF PROTECTION
FOR TB CENTERS, THOSE ARE LOOK
AT BASIC IMMUNE RESPONSES.
REQUIRED FOR PROTECTION AGAINST
TB. LASTLY TESTIFY NO -- CENTERS
FOR ANTIMICROBIAL RHESUS TAN
BACTERIA, INTERDISCIPLINARY
COMBATING ANTIMICROBIAL
RESISTANT BACTERIA
INTERDISCIPLINARY RESEARCH
UNITS. THOSE ARE BASIC RESEARCH
LOOKING AT BACTERIAL AND HOST
FACTORS THAT ARE IMPORTANT FOR
DEVELOPING RESISTANCE AND WE
NEED TO POINT OUT THESE ARE
DESIGNED TO BE PRECETR, MORE OF
THE BAY SUCK RESEARCH AND COULD
POTENTIALLY FEED INTO A CETR BUT
ARE DISTANT. AGAIN CETR 3.0 IS
ABOUT DEVELOPING MEDICAL COUNTER
MEASURES FOR AMR BACTERIAL AND
URGENT FUNGAL THREATS. SO THIS
IS HOW WE ENVISION THE PROJECTS
OR PROPOSALS THAT MIGHT COME IN,
THEY COULD SPAN THERAPEUTICS,
VACCINES AND DIAGNOSTICS SO FOR
THERAPEUTIC APPROACHES WE ARE
THINKING NEW APPROACHES, NEW
THERAPEUTIC APPROACHES FOR
NON-TARGETS SO TARGET DISCOVERY
WAS IN THE (INAUDIBLE) BUT THIS
WOULD BE ADVANCING THAT LOOKING
FOR NEW THERAPEUTIC APPROACHES
FOR THOSE TARGETS. THINKING A
BIT ABOUT ALTERNATIVE
TECHNOLOGIES, FOR EXAMPLE, PHAGE
POTENT YEAH TORRS THAT COULD
RESTORE ANTIMICROBIAL
SUSCEPTIBILITY, THINKING ABOUT
THERAPEUTICS OR THINKING ABOUT
MONOTHERAPIES, COMBINATION,
ADJUDGETIVE THERAPY THE WHOLE
GAMUT. FOR VACCINES SOME
POSSIBLE APPROACHES OR SYSTEMS
VACCINOLOGY FOR IMMUNOGEN
DESIGN, INNOVATIVE VACCINE
TECHNOLOGIES, LAST BUT NOT
LEAST, DIAGNOSTICS, SO ONE OF
THE THINGS WE ARE THINKING ABOUT
HERE IS COUPLE DEVELOPMENT OF
PATHOGEN IDENTIFICATION
TECHNOLOGIES ALONG WITH
PHENOTYPIC SUSCEPTIBILITY
TESTING. SO FOR PATHOGEN
IDENTIFICATION TECHNOLOGIES WE
WOULD LIKE TO SEE SENSITIVE
CULTURAL INTERDEPENDENT
SENSITIVE PATHOGEN TESTING AND
WE THINK THAT PHENOTYPIC TESTING
IS GOING TO BE KEY THERE.
ANOTHER THING WE SHOULD POINT
OUT IS WE ARE ANTICIPATING
CENTERS COME IN PROPOSING
VARIETY OF APPROACHES HERE,
THERAPEUTIC VACCINE OR
DIAGNOSTIC POTENTIALLY COMBINED
TOGETHER THEY DON'T HAVE TO PICK
ONE OR ANOTHER. IN TERMS OF THE
PATHOGENS WE ADAPTED THIS TABLE
FROM THE CDC ANTIMICROBIAL
RESISTANCE THREAT REPORT. SO WE
JUST FOCUSED ON FOR BACTERIA
THEIR URGENT AND SERIOUS THREATS
HERE. I WON'T GO THROUGH THIS
WHOLE LIST. FUNGI AS WELL R. FOR
COUNCIL FEEDBACK, WE WANT TO
THANK DR. TAYLOR AND
BOCKENSTEDT, THEY AGREED ON
FOCUSING CETRs ON
ANTIMICROBIAL RESISTANCE, IT WAS
IMPORTANT AND TIMELY ESPECIALLY
GIVEN THAT WE ARE MERGING OUT OF
THE COVID-19 PANDEMIC AND IT IS
TIME TO RE-EMPHASIZE
ANTIMICROBIAL RESISTANCE. ONE OF
THE QUESTIONS THEY ASKED WAS
WITH RESPECT (INAUDIBLE) SHOULD
BE INCLUDED, THAT IS CERTAINLY
-- IT WAS -- THERE WAS A RECENT
CDC HEALTH ALERT AROUND VIBRIAL
IN PARTICULAR WARMING COASTAL
WATERS, SO THEY -- ASKED WHETHER
WE SHOULD CONSIDER WORKING THIS
ON THE LIST. RIGHT NOW IT IS
CONSIDERED AMR PATHOGEN BY CDC
SO IT IS TECHNICALLY NOT ON THE
LIST, WE ARE GOING TO TALK WITH
CDC AND WATCH WHETHER THEY MIGHT
CONSIDER ADDING IT TO THEIR
WATCH LIST, AS OF RIGHT NOW WE
ARE NOT GOING TO CONSIDER IT
RESPONSIVE AT THIS POINT IN
TIME. IT IS AN EXCELLENT POINT
THOUGH THAT CLIMATE CHANGE IS
IMPACTING THREATS ANTIMICROBIAL
THREATS THAT WE FACED. BACK TO
THE ORIGINAL SLIDE, WE ARE
THINKING FOUR TO SIX AWARDS
USING THE U 19 MECHANISM FOCUS
CANNING ON ANN MICROBIAL
RESISTANCE.
>>QUESTIONS FROM COUNCIL
MEMBERS, DR. PALMER, YOU ARE
LINING UP ON THE SCREEN, I DON'T
KNOW IF YOU WANT TO SAY
SOMETHING. NO? OKAY. DR.
JERNIGAN YOU HAVE YOUR HAND UP?
>>JUST HAPPY TO CONNECT YOU IN
WITH THE DIVISION OF FOOD BORN
WATER BORNE AND ENVIRONMENTAL
INFECTIONS WITH REGARD TO
VIBRIO, (INAUDIBLE) REALLY
INCREASE BECAUSE OF THE
INCREASED TEMPERATURE OF WATER.
I DON'T BELIEVE THEY ARE
PLANNING TO ADD THAT TO THE AIM
OR LIST BUT HAPPY TO CONNECT
MICHAEL CRAIG AND OTHERS ON
THAT.
>>EXCELLENT. PROBABLY WORTH
MENTIONING SINCE THERAPEUTICS,
WE ARE ACTIVELY SOLICITING GRAM
NEGATIVE FOCUS, SO ANYTHING THAT
COMES UP AS A THREAT THAT
EMERGES BETWEEN NOW AND THE NEXT
POTENTIAL DRUG WE COULD PUT THEM
INTO PRE-CLINICAL SERVICE
TESTING AND SEE HOW WHY THEIR
ACTIVITY WOULD BE EXPECTED TO BE
SO THERE IS LOT OF WAYS WE CAN
HANDLE THIS PROBLEM. THANK YOU,
JUDY. I DIDN'T SEE HANDS GO UP.
>>SO WE CAN MAKE SURE ANY
QUESTIONS.
>>WERE THERE ANY QUESTIONS, ANY
FURTHER QUESTIONS FROM THE
COUNCIL MEMBERS WHO ARE ONLINE?
I DIDN'T SEE THE WHOLE GALLERY.
DR. BOCKENSTEDT IS SHAKING HER
HEAD. THANK YOU. NEXT IS DR.
REEDE SHABMAN, CONCEPT FOR
CLEARANCE FROM OD SET.
>>WHILE WAITING FOR SLIDES TO
COME UP I WOULD LIKE TO THANK
YOU FOR THE OPPORTUNITY TO
PRESENT AND PRESENTING ON OFFICE
OF DATA SCIENCE EMERGING
TECHNOLOGIES AND DEPUTY DIRECTOR
ABOUT TEN MINUTES AGO. AND I WAS
IN DMID PREVIOUSLY, WORKING WITH
LILLIANA, HAVE AN OPPORTUNITY TO
PRESENT. TODAY I WANT TO TALK
WITH YOU SWITCH GEARS AN CHAT
WITH YOU BRIEFLY ABOUT FY 25
CONCEPT, CENTER OF EXCELLENCE
FOR SYSTEMS MODELING INFECTION
IMMUNITY ACROSS BIOLOGICAL
SCALES. AND THE OBJECTIVE OF
THIS CONCEPT IS TO ADVANCE
INFECTIOUS AND IMMUNE MEDIATED
DISEASE MODELING RESEARCH AND
COORDINATION AND WE WILL DO THIS
THROUGH RESEARCH PROJECTS AND
COORDINATION CORES SO THE
RESEARCH PROJECTS WILL IMPROVE
METHODS FOR MODELING COMPLEX
SYSTEMS RELATED TO INFECTIOUS
AND ALLERGIC AND IMMUNE MEDIATED
DISEASINGS ACROSS DIFFERENT
BIOLOGICAL SCALE SCALES. COORDIN
CORES WE WILL GET INTO MORE
DETAIL ON THE FOLLOWING SLIDES
WILL IMPROVE COLLABORATION
COORDINATION DATA MODEL SHARING
AND TRAINING AND ALIGN MODELING
WITH NIAID STRATEGIC PRIORITIES
SO THIS IS A U 54, THIS IS A NEW
CONCEPT FIVE YEARS, WE ARE
ANTICIPATING A SINGLE CENTER OF
EXCELLENCE OR COE. I WOULD LIKE
TO STOP HERE AND ACKNOWLEDGE I'M
PRESENTING ON A LARGE ON BEHALF
OF LARGE NUMBER OF FOLKS, ODSET
WHICH IS SITS IN THE OD. THIS
IS JOINT INITIATIVE WITH DMID,
OVER HERE, SPEARHEAD AD LOT BY
(INAUDIBLE) BROWN, DADE ALLISON
CANDIDATES CARLY WILLIAMS, JASON
HEIGHT AND PETER KIM. THIS IS
GOING TO SPAN ALL THREE PROJECTS
ALL THREE DIVISIONS. SO LITTLE
BIT OF BACKGROUND. I WANT TO
TALK ABOUT SYSTEMS MODELING AND
HOW TO IMPROVE UNDERSTANDING OF
COMPLEX BIOLOGICAL MECHANISMS.
IN GENERAL A MODEL IS A
RECOMMENDATION OF REALITY
EXPRESSED THROUGH MATHEMATICAL
OR LOGICAL RELATIONSHIPS. THE
SYSTEMS MODEL IS A COMPUTATIONAL
MECHANISTIC RECOMMENDATION OF
COMPLEX PROCESS SUCH AS
INFECTION PROCESS ACROSS THE
CELL, T-CELL ACTIVATION AND
EPIDEMIC OR TRIAL. SO THERE
COULD BE A LARGE NUMBER OF
EXAMPLES WE CAN SHOW ON THE
SLIDE IS A PAPER THAT DEFINE AS
PERIOD OF TIME BETWEEN MID
OCTOBER AND MID NOVEMBER OF 2019
AS PLAUSIBLE INTERVAL OF THE
FIRST CASE OF SARS COV-2 CASE IN
CHINA. BY CHARACTERIZING THE
DYNAMICS OF THE VIRUS BEFORE
DISCOVERY THE OFFICERS SHOWED
MORE THAN TWO-THIRDS OF SARS
COV-2 EVENTS SELF-LIMITED,
NEGATIVE PANDEMIC, DONE THROUGH
DATA STREAMS AND PUTTING INTO
THESE TYPES OF MODELS THIS IS
DISTINCT FROM USING A
COMPUTATIONAL MODEL EPIDEMIC
FORECASTING FOR EXAMPLE. A
LITTLE BACKGROUND, IT WOULD COME
NO SURPRISE FUNDING SIGNIFICANT
AMOUNT OF MODELING RESEARCH,
THAT RESEARCH WILL BENEFIT FROM
CORD NATION. SO WE LOOK AT DATA
A LOT OF WAYS AND I SAY THE WORD
NUMEROUS DEPENDING HOW YOU
ANALYZE YOU GET A LARGE NUMBER
BUT LARGE AWARDS MODELING
PROJECT, AS WE LOOK THROUGH FY
21 THROUGH 23, MANY ARE
INVESTIGATOR INITIATED. MOREOVER
30% MODELING IS AFFILIATE WITH
THE MIDAS NETWORK AND FUNDED BY
NIAID ANDLY SPEAK ABOUT THAT IN
A MOMENT. THERE IS LIMITED
COORDINATION TO SHARE METHODS
MODELS OR DATA ACROSS PATHOGENS
AND RESEARCHERS SO SOME EXAMPLES
OF THESE AWARDS IF YOU LOOK YOU
CAN SEE EXAMPLE OF MODELING HIV
RESERVOIR CANDIDATES MODELS HOST
MICROBIOTA, INTERACTION WITH --
AUTOMICROBIOME TRANSPLANTS AND D
MID AND MODELING TISSUE RESIDENT
T-CELLS IN DADES. SPEAKING TO
IMPORTANCE OF HAVING A U 54,
COORDINATION WILL IMPROVE
COLLABORATION NEW METHODS AS
WOMEN AS DATA MODEL SHARING AND
REPRODUCIBILITY. SO THE GAO
CITED THE NEED FOR COORDINATING
INFECTIOUS IMMUNE MEDIATED
DISEASE MODELINGING. THIS IS WIY
RECOGNIZED IN 2020, PARAPHRASE
WHAT THIS REPORT FOUND IS
ESSENTIALLY THEY STATE MODELS IN
INFECTIOUS DISEASE GUIDE
DECISION MAKERS POLICIES FOR
DISEASE CONTROL AND MAY HELP TO
ALLOCATE RESOURCES. HHS AGENCIES
REPORTED USING MULTIPLE
MECHANISMS TO COORDINATE
MODELING EFFORTS ACROSS AGENCIES
BUT DO NOT EVALUATE EXTENT AND
SUCCESS OF COORDINATION. SO
CONSEQUENTLY THE RISK MISSING
OPPORTUNITIES TO ADDRESS
MODELING CHALLENGES SUCH AS
COMMUNICATING CLEARLY, OBTAIN
ADEQUATE DATA AND RESOURCES
OUTBREAK AND DUPLICATION OF
AGENCY MODELING EFFORTS WHICH
LEAD TO INEFFICIENCIES. ON THE
RIGHT HAND SIDE IS PERSPECTIVES
IN SCIENCE CITED A NUMBER OF
TIMES DESCRIBING REPRODUCIBILITY
RESEARCH AND COMPUTATIONAL
SCIENCE. THE SCIENCE LED TO
EXCITING DEVELOPMENTS BUTNA
ITURE OF THE WORK IS EXPOSE
LIMITATIONS TO EVALUATE
PUBLISHED FINDINGS. SO IN OTHER
WORDS REPRODUCIBILITY HAS SERVED
AS MINIMUM STANDARD FOR JUDGING
SCIENTIFIC CLAIMS WHEN FULL
INDEPENDENT REPLICATION OF STUDY
IS NOT POSSIBLE SO WE CAN HAVE
REPRODUCIBILITY IN OUR MODEL MOS
WOULD BE A GOOD PLACE TO STRIVE.
HOW WOULD THIS -- WE START TO
ATTACK THESE CHALLENGES? THIS IS
HIGH LEVEL OVERVIEW HOW A SINGLE
CENTER OF CLEANSE COE SUPPORT
MULTIPLE PIs THROUGH EXPERTISE
AND MODELING RESEARCH AND
COORDINATION. SO ON THE LEFT IS
CURRENT STATES, MECHANISMS,
OBVIOUS WILL MORE, WE HAVE NIAID
SUPPORTED MODELING RESEARCH. IF
YOU GO ACROSS THE TOP, HERE YOU
SEE THIS COE WILL BE NIAID POINT
OF CONTACT IN RESOURCE FOR IAD
MODELING. THIS WOULD OCCUR
THROUGH CORES I MENTIONED.
CONSIDERING A MODEL OF DATA
SHARING CORE, COMMUNITY
DEVELOPMENT CORE, AS WELL AS
PLACE FOR OPPORTUNITY FUNDS.
THESE CORES ARE GOING TO ENGAGE
WITH THE RESEARCH COMMUNITY TO
HELP THESE INVESTIGATORS SPEAK
TO EACH OTHER ABOUT HOW THEY ARE
SHARING MODELS AND DATA AND
MAKING SILOED EFFORTS MORE
CONNECTED. BUT COE GO BEYOND
COORDINATION, ALSO DRAW CUTTING
EDGE RESEARCH SO IN THE C 54
RESEARCH PROJECTS A COUPLE OF
REQUIRED PROJECTS AND OPTIONAL
PROJECT WHERE WE EXPECT CUTTING
EDGE TECHNOLOGIES AND MODELING
SPACE. ALL THIS TIE INTO THE
NIAID DATA ECOSYSTEM PORTAL ON
THE BOTTOM HERE, RECENTLY
LAUNCHED PORTAL THAT IS AN
AGGREGATOR OF DIGITAL ASSETS
FROM NIAID AND OTHERS SUPPORTED
INFECTIOUS DISEASE AND IMMUNE
MEDIATED DISEASE DATA. THIS IS A
LOT OF FEW BULLETS HERE BUT TRY
TO GO INTO MORE DETAIL WHAT THE
RESEARCH PROJECTS ENCOMPASS. SO
FOR EXAMPLE, THE RESEARCH
PROJECTS WOULD BRIDGE
COMPUTATIONAL MODELS AT
DIFFERENT BIOLOGICAL SCALES. FOR
EXAMPLE MOLECULAR AND CELLULAR
MODELS TO WITHIN HOST MODELS.
THEY CAN ALSO BRIDGE SCALES FROM
WITHIN HOST BETWEEN HOST MODELS
FOR PATHOGEN SPREAD FOR EXAMPLE.
THESE PROJECTS WOULD EVALUATE
HOW DETERMINANTS OF ONE SCALE
INFLUENCE OUTCOMES AT ANOTHER.
PROJECTS TO TRANSLATE FROM BASIC
SCIENCE POPULATION LEVEL
OUTCOME, THEY WOULD COVER
INFECTIOUS DISEASE ALLERGIC
MEDIATED DISEASE, IMMUNOLOGY,
HIV INCLUDED IN AT LEAST ONE
PROJECT SINCE THIS IS
COLLABORATION WITH DAID, IS.
DOESN'T HAVE TO BE THE ENTIRE
PROJECT. OF COURSE PRIORITIES
WITH CIRCLE AROUND AND NOT BE
LIMITED TO VACCINES AND
MICROBIALS, STRUCTURAL LEVEL
FACTORS WHICH ARE BECOMING MORE
IMPORTANT SUCH AS CLIMATE
CHANGE. TO REITERATE ON THE
COORDINATION CORE THERE IS IS
ADMINISTRATION ELEMENT, FROM
THIS U 54 AND WE EXPECT THESE
CORES TO DEVELOP INNOVATIVE
METHODS FOR DATA AN MODEL
SHARING THAT ENABLE REUSE. WHAT
MIGHT GO BEYOND TRADITIONAL WAYS
OF SHARING BESIDES PUTTING
SOMETHING ON GITHUB MAYBE LOOK
FOR SOMETHING MORE INNOVATIVE
AND FOSTER COMMUNITY THROUGH
WORKSHOPS AND OPPORTUNITY FUNDS.
VERY IMPORTANT IS THE COE SHOULD
BE ABLE TO PIVOT RESEARCH AND
COORDINATION DURING EPIDEMICS
AND PANDEMICS TO ALIGN WITH THE
PRIORITIES OF THE INSTITUTE. SO
THIS IS A SLIDE I'M PUTTING IN
WHICH IS RESPONSE TO SOME OF THE
COUNCIL FEEDBACK. I APPRECIATE
THAT, GET TO THAT ON THE NEXT
SLIDE, NIAID COE WILL SUPPORT
THE NIAID MISSION IN CONTEXT
SHOULD HAVE ACTIVITY AND
COMPLIMENT EXISTING PROGRAMS SO
THE POINT OF THIS SLIDE IS THAT
THERE ARE A LOT OF DIFFERENT
EFFORTS OUT THERE. HOWEVER WE DO
BELIEVE THE COE HAS UNIQUE PLACE
THAT SHOULD BE SUPPORTED. FOR
EXAMPLE WE SPENT A LOT OF TIME
TALKING THE INDIVIDUAL AWARDS IN
NIAID, RIGHT NOW WE THINK THEY
CAN BE ORGANIZED MORE
EFFICIENTLY. THERE IS MIDAS
NETWORK, CONSISTING OF A SINGLE
U 24 WHICH IS PRIMARILY
COORDINATION CORES B, MOSTLY
FOCUSED ON COORDINATION AND NOT
NECESSARILY AS NIMBLE TO ALIGN
WITH THE NEEDS OF NIAID. THERE
IS THE INTERAGENCY MODELING AND
ANALYSIS GROUP. THIS IS A CROSS
NIH AND CROSS GOVERNMENT
ORGANIZATION WHICH CURRENTLY IS
IN SUPPORTED ANY ACTIVE AWARDS.
THERE ARE OTHER OUTSIDE OF
NIAID, THE CENTER FOR
FORECASTING AN OUTBREAK
ANALYTICS. THE DARPA ASKING
PROGRAM, LARGE IMPRESSIVE
PROGRAMS, FOCUSED ON
EPIDEMIOLOGY. THERE IS THE
ECOLOGY EVOLUTION OF INFECTIOUS
DISEASES WHICH NIAID WORKS WITH
AS WELL AS GATES FOUNDATION. SO
THESE EXIST AND WE BELIEVE THE
COE WILL COORDINATE WITH THESE
PROGRAMS BUT ALSO DISTINGUISH
ITSELF THROUGH SUPPORTING THE
NIAID MISSION THROUGH MODELS
THAT ARE GOING TO DIRECTLY
INFORM US ABOUT BETTER VACCINES
DIAGNOSTICS AND THERAPEUTICS.
AND ALSO BE ABLE TO PIVOT
TOWARDS THEIR INFRASTRUCTURE,
HOW INFRASTRUCTURE THAT CAN
PIVOT DURING EPIDEMICS AN
PANDEMICS. SO ONE OTHER THING
TO POINT OUT HERE, IN OUR
OFFICE, AND OTHERS IS THIS
ACCOMPANYING NOCI. THE REASON WE
ARE APPOINTING NOCI HERE IS
SYSTEMS MODELING OF INFECTION
IMMUNITY ACROSS BIOLOGICAL
SCALES AND THE POINT IS TO
ENCOURAGE RO1 AND R21
APPLICATIONS FOR SYSTEMS
MODELING AND ENCOURAGE AWARDEES
TO COLLABORATE WITH THE COE.
AWARDEES ELIGIBLE FOR
OPPORTUNITY FUNDS IN COE JOIN
MEETINGS, WORKSHOPS ET CETERA.
THIS IS PAY LINES, DEPEND HOW
WELL THEY DID IN REVIEW BUT IDEA
IS TO INCREASE THE NUMBER OF
INVESTIGATORS THAT WOULD BE
SUBMIT RESPONSIVE APPLICATIONS
TO INTERACT WITH THE COE. SO THE
COUNCIL FEEDBACK WE HAVE THE
OPPORTUNITY TO SPEAK WITH DR.
JERNIGAN AND PALMER AND GREAT
CONVERSATION WITH BOTH. THEY
WERE SUPPORTIVE OF THIS CONCEPT.
FEEDBACK INCLUDED TO FOCUS TO
MODEL IAD ACROSS BIOLOGICAL
SCALES REPRESENTS AN EXCITING
CHALLENGE IN THE FIELD. ALSO
NOTESSED THE POTENTIAL SCOPE
ACROSS ALL SCALES IS LARGE. I
TEND TO AGREE WITH THAT. BUT IT
IS ALSO EXCITING CHALLENGE. THEY
THOUGHT MAYBE WE SHOULD CONSIDER
EMPHASIZING SPECIFIC SCALES OVER
OTHERS. IT IS ALSO IMPORTANT TO
CONSIDER HOW THE COE INTEGRATES
TO EXISTING MODELING PROGRAMS
AND THIS IS A IMPORTANT POINT,
WE DON'T WANT TO -- BASED ON
WHAT WE PRESENTED EARLIER DON'T
WANT TO REINVENT THE WHEEL, THIS
IS POSITIONED TO FIT INTO THE
LARGER ECOSYSTEM OF MORE
PROGRAMS ACROSS THE GOVERNMENT,
IMPORTANT TO ENCOURAGE JUNIOR
INVESTIGATORS EARLY STAGE
INVESTIGATORS SINCE TETANUS
SPACE IS COMPUTATIONAL AND A LOT
OF TIMES IS SITUATED IN THE MORE
JUNIOR FOLKS. FINAL SLIDE,
RELATED BUT LITTLE BIT ON THE
SIDE, THIS IS A HEADS UP FOR A
NOTICE OF SPECIAL INTEREST FOR
COMPETITIVE REVISION SUPPLEMENT
FOR COMPETITIVE REVISION
SUPPLEMENTS TO EXISTING T 32
PROGRAMS TO INCLUDE
INSTITUTIONAL RESEARCH TRAINING
AND DATA SCIENCE FOR INFECTIOUS
IMMUNE MEDIATE DISEASE. WE
WANTED TO INCLUDE THIS BECAUSE
THERE IS A NEED TO MEET -- TO
MEET THE GROWING NEED FOR IUD
RESEARCHERS WITH -- IID
RESEARCHERS WITH DATA SCIENCE
EXPERTISE NEEDS TO BE DONE BY
CREATING NEW SLOTS FOR
PRE-DOCTORAL TRAINEES IN
EXISTING T 32 PROGRAMS, THESE
TRAINING PROGRAMS WILL ESTABLISH
INSTITUTIONAL LEVEL
COLLABORATIONS BETWEEN
COMPUTATIONAL AND BIOMEDICAL
SCHOOLS FOR MULTI-DISCIPLINARY
COURSE WORK AN DISSERTATION
RESEARCH. THE IDEA HERE IS
ESSENTIALLY THAT YOU CAN CREATE
NEW COARSE WORK TO INCLUDE
NATURAL LANGUAGE PROCESSING
MACHINE LEARNING ARTIFICIAL
INTELLIGENCE FOR INDIVIDUALS
GETTING THEIR Ph.D.s SO THAT
THEY CAN START TO APPLY SKILL
SETS TO OTHER INFECTIOUS DISEASE
RESEARCH. I HOPE I WAS ABLE TO
SUMMARIZE A LOT OF DIFFERENT
EXCITING OPPORTUNITIES, COUPLE
OF EXCITING CONCEPTS GOING ON
HERE. I FINISHED WITH THE FINAL
SLIDE FOR THE U 54. I THINK I
WOULD BE HAPPY TO ADDRESS ANY
QUESTIONS YOU MAY HAVE. THANK
YOU VERY MUCH.
>>I WOULD TO POINT OUT OFFICE O
DIRECTORS IS ONLINE AS WELL.
>>THERE'S TWO PROJECTS THAT
(INAUDIBLE) WONDERING THERE IS
QUITE A BIT OF (INAUDIBLE)
DEVELOP, WONDERING HOW EXAMPLES
OF ONE TYPE OF PROJECTS, FOR
WONDERING IF TWO PROJECTS MIGHT
BE CONSTRAINED IMAMMING DATA
ACCUMULATION, WHAT IS GOING TO
FIT, (INAUDIBLE) IN OTHER WORDS
WILL THE MODELING BE DEVELOP
DIVORCED FROM EXISTING DATA?
(INAUDIBLE) THEN A LITTLE BIT
WONDERING ABOUT AND THINKING
VARIOUS GENERAL MODEL SYSTEMS,
IMAGE LIKE HOW DO YOU GUYS
(INAUDIBLE)
>>I SEE A LOT OF POTENTIAL
HERE, I'M JUST WONDERING HOW
THEY CAN BE A BIT MORE FOCUSED.
>>REALLY GOOD POINTS THERE. I
THINK HIGH LEVEL THIS IS A
SINGLE CENTER WITH COUPLE OF
RESEARCH PROJECTS SO WE EXPECT
EXPERTISE TO BE BROAD. AND WE
WANT FOLKS WITH LOT OF DIFFERENT
AREAS. IF I UNDERSTAND YOUR
QUESTION CORRECTLY, WE WANTED
COMBINATION, SO WE WANT A
SITUATION WHERE PRIMARY FOCUS OF
THIS IS GOING TO BE INGESTION
AND MODELING OF EXISTING DATA.
WHERE GENERAL RATION NEW DATA
USED FOR VALIDATION. AND WITH
RESPECT TO FOCUS, YOU CAN
ENVISION, THINKING LOUT WOULD
BUT ENVISION A SCENARIO ONE
PROJECT WOULD BE ON IMMUNE
MEDIATED FUNDING IMMUNE SYSTEM
DIGITAL TWIN FOR EXAMPLE HOW
THAT -- HOW THAT COULD BE
UNDERSTOOD IN THE CONTEXT OF A
PATHOGEN OR IMMUNE MEDIATED
DISEASE, POTENTIALLY ANOTHER
RESEARCH PROJECT ON A VIRUS OR
BACTERIA AND HOW IT CAN INTERACT
IN A HOST CELL IN A LARGE --
SORT OF BRIDGE THAT WITH A
LARGER SCALE SUCH AS ORGAN
SYSTEM OR BEYOND. IT IS A GOOD
QUESTION ABOUT SCOPE, BROUGHT UP
WITH COUNCIL MEMBERS AS WELL. IT
IS ALSO SOMETHING WE ARE
DISCUSSING INTERNALLY, I THINK
THAT IS WORTH MENTION.
>>DO YOU HAVE ANY OTHER
THOUGHTS ON THAT QUESTION?
>>NO, THANKS, REED. YOU
ADDRESSED IT, IT IS A BIT OF
CHALLENGE BECAUSE THIS IS
TRANSNIAID INITIATIVE AND ALWAYS
THREE ARE PARTICIPATING SO WILL
BE REQUIRED IN THE SCOPE TO
ADDRESS HIV AND ASPECTS OF HIV
BECAUSE OF THE DATA INVOLVEMENT.
THEN BECAUSE THERE'S ALSO DATA
IN DMID, WE WILL PUT
REQUIREMENTS IN PLACE IN TERMS
OF WHAT TYPES OF BRIDGES NEED TO
BE BUILT BETWEEN GENOMIC SCALES
AND THEN HOLD THAT -- HOPE
INVESTIGATORS COME IN WITH
PROJECTS. THAT WOULD FIT.
CONSTRAINTS ARE HIGH LEVEL
BECAUSE BIG SCOPE IN THE
COMMUNITY RIGHT NOW WE TRYING TO
ADDRESS.
>>DR. BOCKENSTEDT I SEE YOUR
HAND IS UP. I SEE. DR. PALMER.
>>WE CAN BE INTERCHANGEABLE
THAT IS OKAY. I WANT TO
EMPHASIZE WHAT IS UNIQUE IS
WORKING ACROSS SCALES SO I'M
TRYING TO THINK OF SPECIFIC
EXAMPLES, WE UNDERSTAND HOW
SUPER SHEDDERS FOR PATHOGEN THEN
AFFECT SPREAD THROUGHOUT A
COMMUNITY BUT LINKING THAT BACK
TO WHAT IS THE NETWORK AT THE
IMMUNE LEVEL WITHIN AN
INDIVIDUAL THAT CREATES THE
SUPER SPREADER AND THEN ALLOWS
SPREAD THROUGHOUT THE COMMUNITY
AND HOW EXTERNAL FACTORS OF THAT
COMMUNITY ALLOW THAT SUPER
SPREADING EVEN TO OCCUR. SO IT
IS REALLY POTENTIALLY VERY
IMPACTFUL, IT IS A BIG CHALLENGE
TO WORK ACROSS THOSE SCALES,
MOST DATA SCIENTISTS PREFER TO
WORK WITHIN ONE OF THOSE SILOS
BUT WHAT THIS DOES THAT IS
REALLY UNIQUE AND I FOUND QUITE
INNOVATIVE, WAS THE EMPHASIS ON
WORKING ACROSS DIFFERENT SCALES.
THAT IS WHAT STANDS OUT, WHY IT
IS NOT JUST ANOTHER DATA SCIENCE
PROGRPROGRAM. THIS HAS REALLY GT
THIS FOCUS ON MOVING ACROSS
SCALES WHICH COULD GIVE A LOT OF
INSIGHT TO WHY EMERGING
PATHOGENS RELATE -- BECOME
PANDEMICS AND OTHERS DIE OUT,
WHETHER THAT IS OCCURRING AT THE
INDIVIDUAL LEVEL SCALE,
COMMUNITY LEVEL SCALE OR THAT
INTERACTION BETWEEN THE TWO.
THAT IS WHAT THIS INITIATIVE
REALLY ADDRESSES. I'M VERY
ENTHUSIASTIC ABOUT THIS.
>>THANK Y THANK YOU. MORE COMMR
QUESTIONS?
>>SO EVERYONE WHO IS A COUNCIL
MEMBER PLEASE RECORD YOUR VOTES
ON EACH INDIVIDUAL CONCEPT IN
THE ELECTRONIC COUNCIL BOOK. IF
YOU FORGET PEOPLE WILL COME
AFTER YOU AND REMIND YOU. BUT
THIS DOES CONCLUDE OUR OPEN
SESSION OF THE DMID SUB COUNCIL.
THANK YOU TO EVERYBODY AND WE
WILL RECONNECT VIRTUALLY IN
JANUARY. THANK YOU.