I THINK WE HAVE EVERYBODY
ASSEMBLED HERE AND OUR KEY
MEMBERS PARTICIPATING REMOTELY
ARE ON THE SCREEN.
I WILL GET STARTED.
I WILL GIVE A BRIEF REPORT TO
OUR SUBCOMMITTEE HERE IN THE
PUBLIC SESSION EMPLOY NEXT
SLIDE, PLEASE.
ON THIS SLIDE YOU WILL SEE THE
AGENDA FOR THIS AFTERNOON, I
WILL START WITH A PERSONNEL
UPDATE I WILL TALK AND HIT
HIGHLIGHTS OF OUR RECENT
RESEARCH NEWS AND THEN YOU WILL
HEAR AN UPDATE ON THE SEER
RESPONSE TO THE NH51 N1
INFLUENZA OUTBREAK BY LAUREN
BERG LEOTIS, AND THEN WE WILL
MOVE ON FOR PRESENTING OUR
CONCEPT CLEARANCE FOR YOUR
CONSIDERATION AND THE 5 CONCEPTS
WE WILL THINK ABOUT ARE
PRESENTED ON THIS AGENDA SLIDE.
SO INCOME SLIDE, PLEASE IT'S
SOMETIMES HARD TO HIRE PEOPLE
AND WE'VE HAD A LOT OF SUCCESS
SINCE THE LAST TIME WE MET IN
BRINGING NEW PEOPLE ONBOARD SO
I'LL GIVE YOU BITS ABOUT EACH OF
THE NEW DMID STAFF, CYNDA HALL
IS A NURSE OFFICER WHO JOINED
THE OCRREFRESH YOUR
RECOLLECTION TEAM AS A NURSE
CONSULTANT AND PROGRAM OFFICER.
SHE COMES TO US FROM THE OFFICE
OF THE ASSISTANT SECRETARY FOR
HEALTH.
ALSO KNOWN AS OASH, AND THE
POPULATION OF AFFAIRS WHERE SHE
WAS A PROJECT OFFICER FOR FAMILY
BLANKING GRANTS ACROSS MULTIPLE
REGIONS IN THE UNITED STATES.
AND THEN TOM DIMAGGIO IS ANOTHER
NURSE FROM THE INTRAMURAL
PROGRAM, IN THE LAB OF CLINICAL
AND MICROBIOLOGY WHERE HE WAS A
CLINICAL RESEARCH SPECIALIST.
HE HAS MORE THAN 20 YEARS OF
EXPERIENCE IN CLINICAL RESEARCH,
HE'S GOING TO BE SUPPORTING
PHASE 1 AND 2 CLINICAL TRIALS
THROUGH OBRTRTR, THROUGH
CONTRACTS AND DR. LISA CAZARES
AS JOINED OBRRTR AS A PROGRAM
OFFICER IN THE DRUG DEVELOPMENT
SECTION, SHE RECENTLY, HER MOST
RECENT POSITION WAS AT AFT
RAZENECCA BIOPHARMACEUTICAL
WHERE SHE HAD A DIVERSE
PORTFOLIO INVOLVING RESPIRAT ORY
CARDIOVASCULAR DISEASES WELCOME
TO CYNETWORK DA, TOM, AND LISA,
NEXT SLIDE, PLEASE.
AND I MENTIONED THAT LEOTUS WILL
TALK FOLLOWING MY PRESENTATION
AND AND SHE IS NOW IN THE CENTER
FOR EXCELLENCE AND INFLUENZA AND
RESEARCH AND RESPONSE--A LITTLE
BIT OF BAPTISM BY FIRE, SO THAT
WAS GREAT.
SHE CAME TO US FROM NHLBI WHERE
SHE WAS A PROGRAM OFFICER IN THE
LUNG PULMONARY INFECTIONS
PROGRAM WHERE SHE HAD THOSE TO
THE MICROBIOME AND HIV/AIDS.
BEFORE THAT SHE WAS A WRITER AND
EDITOR IN THE SPECIAL PATHOGENS
BRANCH AT THE CDC, BUT ALSO
MAURI OSHEROFF ICE EDWARDS HAS
JOINED THE PARASITOLOGY AND
INTERNATIONAL PROGRAMS BRANCH AS
A PROJECT MANAGER, HE COMES FROM
NIEHS, THE ENVIRONMENTAL HEALTH
INSTITUTE WHERE HE SERVED AS A
GRANT SPECIALIST AND ASSISTED IN
AS A POST DOC SPECIALIST.
BEFORE THAT HE WORKED AS A GRANT
SPECIALIST, THEIR REVIEW PROGRAM
AND ALSO WORKED WITH RCDC AND
NIH OD.
AND DR. RICKY SONG HAS JOINED
OBRRTR, RECENTLY, HE WILL
SUPPORT ADVANCE PRODUCT
DEVELOPMENT AND PRECLINICAL
SERVICES IN THE DIAGNOSTIC AREA
WHICH WE'RE FRYING TO EXPAND.
YOU PREVIOUSLY WORKED AT MRI
GLOBAL WHERE HE LED PROGECS AND
INVITRO DIAGNOSTICS FOR BOTH
CHEMICAL AND INFECTIOUS DISEASE
APPLICATIONS TO BE PART OF THE
REGULATORY PACKAGES SUBMITTED TO
THE FDA.
NEXT SLIDE, PLEASE.
EVEN MORE DR. [INDISCERNIBLE]
JOINED DMID IN THE PAST WEEK
WHERE SHE WILL SERVE AS THE
PROGRAM OFFICER FOR PRECLINICAL
DESIGN AND CLINICAL TRANSLATION
OF TB REGIMENS, THIS IS A NEW
CONSORTIUM THAT WE'RE FUNDING IN
ADDITION TO A FEW OTHER
SPRBILITYS IN THE MICROBACTERIAL
EXPRESSION, SHE COMES TO US FROM
THE UNIVERSITY OF GEORGIA WHERE
SHE WAS AN ASIFT ANT PROFESSOR
FOR INFECT YOWZ DISEASES AND
WORKED ON IMMUNOLOGIC
DYSFUNCTION AND CLINICALLY
RECOVERED HPV AND IN SARS-COV-2
INDIVIDUALS AND AS WELLsA
FOCUSING ON MICROBACTERIUM
INFECTION.
JEREMY WARNER HAS JOINED THE
OFFICE OF CLINICAL RESEARCH
RESOURCES, AS A PROGRAM ANALYST,
HE COMES FROM SAN DIEGO WHERE HE
WORKED FOR A RESEARCH
ORGANIZATION FOCUSED ON
ARTIFICIAL INTELIENCE POWERED
PATHOLOGY, HE LED THEIR
SCIENTIFIC MARKETING EFFORTS AND
MANAGED PRECLINICAL PATHOLOGY
STUDIES FOR ACADEMIC LABS AND
PHARMA COMPANIES.
AND CATH LYNN LUKE HAS BEEN WITH
US FOR A NUMBER OF YEARS BUT
SHE'S TRANSITIONING FROM
DMID WITHIN THE RESPIRATORY
DISEASE BRARCH WHERE SHE SERVED
AS A SCIENTIST ON MANY OF THE
INFLUENZA CLINICAL TRIALS AND
MOVED TO THE OFFICE OF
REGULATORY AFFAIRS, AND SHOULD
BE A REGULATORY AFFAIRS MANAGER,
AND SHE HAS 20 YEARS EXPERIENCE
IN MICROBIOLOGY AND VACCINE
DEVELOPMENT INCLUDING ACADEMIA,
BIOTECH, INDUSTRY, AS WELL AS
GOVERNMENT.
NEXT SLIDE, PLEASE.
AND THEN 3 NEW DMID STAFF IN THE
OFFICE OF COORDINATION, KNOWN AS
BUGS, THEY'VE BEEN WITH US FOR A
NUMBER OF YEARS BUT THEY'VE
MOVED INTO NEW ROLES.
TRISH STRIKLER [INDISCERNIBLE]
JUST ASSUMED THE ROLE OF THE THE
GRANT OPERATIONS TEAM LEAD,
SHE'S BEEN A PART OF THE OFFICE
SINCE 2007 WHEN SHE CAME TO US
AS A TRIP AAS FELLOW AND WORKED
FOR A NUMBER OF YEARS IN A
FEDERAL POSITION AND THEN MOVED
AWAY, SWITCHED TO A CONTRACTOR
BUT NOW SHE'S COMING BACK
WORKING REMOTELY AS A FEDERAL
ROLE AS TEAM LEAD.
AND ALEX CLARK CAME ON BOARD AS
A CONTRACTOR LAST YEAR BUT NOW
HE'S TRANITIONING TO A FEDERAL
POSITION, HE'S A PROJECT MANAGER
FOR THE CONTRACK, PLANNING AND
EXECUTION TOOL WHICH IS HOW WE
TRACK OUR PRECLINICAL SERVICES
AND OUR PRECLINICAL SERVICE AND
ACTIONS, SO HE'S WORKING WITH
THOSE INFORMATION TECHNOLOGY
SYSTEMS.
AND AMANDA, AS BEEN IN DMID FOR
15 YEARS, SHE'S COMING BACK TO
US AS A HEALTH COMMUNICATIONS
TEAM.
SHE MAKES MOST OF MY SLIDES FOR
ME SO SHE'S VERY EXPERIENCED AND
HAS MOVED ON TO A FEDERAL ROLE.
ONE SLIDE, 1 MORE, DR. ERIC
STEMI, IS THE DIRECT OF THE
BRARCH, HE WILL CONTINUE IN HIS
ROLE FOR INFLUENZA WERE AND
RESPONSE HE'S BEEN A PROGRAM
OFFICER IN RDB FOR A NUMBER OF
YEARS WHERE HE HAD THE CORONA
VIRUS PORTFOLIO AND THEN HE
MOVED INTO THE SEER NETWORK AND
HE NOW WILL BE THE DEPUTY BRANCH
CHIEF IN RDD.
NEXT SLIDE, PLEASE.
SO JUST MOVING ON TO A LITTLE
BIT OF RESEARCH NEWS, SOME
HIGHLIGHTS OF WHAT WE'VE
ACCOMPLISHED AND HAS HIT
THE--EITHER THE PUBLIC, PRESS OR
THE SCIENTIFIC PRESS RECENTLY.
THIS IS JUST TALKING ABOUT HOW
IN THE PAST SEVERAL MONTHS WE'VE
BEEN VERY INVOLVED IN THE HIGH
PATH OUTBREAK IN DAIRY KALGT.
WE KNOW THIS HAS BEEN A VIRUS
THAT'S BEEN CIRCULATING IN BIRDS
AND HAS IMPACTED SOME MAMMALIAN
POPULATIONS OVER THE PAST
SEVERAL YEARS WITH 1 CASE
DETECTED IN A POULTRY WORKER IN
2022, BUT THEN THE DAIRY KALGT
OUTBREAK THAT WAS ANNOUNCED IN
MARCH 2024, IN THE TEXAS
PANHANDLE CAUGHT A LOT OF US
OFFGUARD BECAUSE WE DEPARTMENT
THINK THIS I HAVE WOULD REALLY
DO ANYTHING IN CATTLE, NEXT
SLIDE, YOU WILL HEAR MORE
DETAILS IN THIS IN LAWRENCE
PRESENTATION BUT THE SLIDE JUST
SUMMARIZES SOME OF THE HIGH
LEVEL EVENTS THAT WE HEARD ON
MULTIPLE CONFERENCE CALLS OVER
THE PAST SEVERAL MONTHS, THERE
HAVE BEEN 3 WITH THE CURRENT
DAIRY KALGT OUTBREAK IN PEOPLE
WHO HAVE PROBABLY HAD CLOSE
EXPOSURE TO DAIRY CATTLE, BUT
NOT A LOT OF TESTING BEING DONE
ON SOME OF THESE FARMS JUST
BECAUSE OF THE FARMERS AND MANY
WORKERS REGARD THE GOVERNMENT
AND THEY'RE NOT INVITED ON TO
THE FARMS TO TEST SO EVEN
SYMPTOMATIC CASES FOR EXAMPLE,
THERE IS A LOT OF WORK AT BARTA,
THAT ARE THOUGHT TO BE
PROTECTIVE THAT HAVE ALREADY,
THE CASE OF SOME OF THESE
COMPANIES BEEN LICENSED FOR USE
SO THIS WILL BE A STRAINCHL
CHANGE COMPARED TO PREPANDEMIC
H5 N1 STRAINS THAT HAD
PREVIOUSLY BEEN TESTED IN HUMANS
SO BARTA IS WORKING WITH
COMPANIES TO MANUFACTURE AND
TEST SOME OF THESE HHIV N1
CANDIDATES AND THE INVITRO
TESTING THUS FAR INDICATES THAT
THESE ARE VERY CLOSELY RELATED
TO THE VIRUS CIRCULATION AND
SHOULD PROTECT INDIVIDUAL WHO IS
GET VACCINATED SHOULD THAT TYPE
OF OF RESPONSE BE REQUIRED TO
PUBLIC HEGHT.
RIGHT NOW THERE'S PROBABLY
ENOUGH BEING MANUFACTURED FOR
ABOUT--ABOUT 10,000,001st
REPONDERS BUT ONCE THE SEASONAL
PRODUCTION FOR INFLUENZA VACCINE
IS CONCLUDED, THERE IS THE
CAPACITY TO RAMP UPLARGE SCALE
PRODECLARATION IF NOTHING.
SO NEXT SLIDE EMPLOY SO JUST A
FEW HIGHLIGHTS FROM CLINICAL
TRIALS THAT DMID SUPPORTED SINCE
THE LAST TIME WE MET IN JANUARY.
THERE WERE INTERIM RESULTS
ANNOUNCED, AND AN ONGOING OR THE
CONSORTIUM OR THE IDRCD, THIS
COMPARED TO THE
PENTAVALENTINEDDENT CONJUGATE
VACCINE AND IT INOCULATED
CHILDREN IN AFRICA WITH THE
VACCINE AND INDICATED IN THE
NINTH MONTH IT WAS SAFE AND
EFFECTIVE SO THE W. H. O. GROUP
THAT MAKES RECOMMENDATIONS FOR
THE WORLD ACTUALLY IN
VACCINATION, RECOMMENDED THIS
ROLL OUT IN THE MENIGE JIETIS
BELT OF AFFRIC ASO IT'S BASED
UPON THOSE RESULTS.
AND THEN THE MOMMY VX STUDY
FOUND THAT WHEN PREGNANT WOMEN
RECEIVED A COVID VACCINE THEIR
INVANTS HAD MUCH PROTECTION
AFTER BIRKT SO THIS IS THE STUDY
ENROLLED A NUMBER OF MATERNAL
INFANT DIADS AND OVER 475
INFANTS THAT WERE BORN--SORRY
EITHER DO DOSES DURING PREGNANCY
OR A BOOST DURING PREGNANCY THE
DATA INDICATE THAD DURING THE
INFANTS THAT WERE IN THE FOLLOW
UP VISIT WERE BETTER PROTECTED
WHEN THERE WAS A BOOST DURING
PREGNANCY.
NEXT SLIDE, PLEASE.
YOU HEARD FROM DR. MIKE ISON THE
LAST TIME WE MET ON HIS TB
UPDATE THAT WE WERE WORKING ON A
STRATEGIC PLAN FOR TUBERCULOSIS
RESEARCH, SO THIS WAS AN NIH
WIDE PLAN, THAT PLAN WAS
RELEASED ON WORLD TB DAY WHICH
WAS MARCH 24th SO PLEASE TAKE
A LOOK AT THAT AND LEARN WHAT WE
PROPOSED TO DO OVER THE NEXT 5
YEARS IN ORDER TO TACKLE THE
NUMBER 1 GLOBAL KILLER IN INFECT
YOWSES DISEASES AND THEN JUST A
LITTLE BIT INFORMATION ON OUR
EFFORTS TO DEVELOP A MORE
BROADLY PROTECTIVE, BROADLY AND
DURANNABLILY PROTECTIVE
INFLUENZA VACCINE, RESEARCH THAT
WAS SUPPORTED BY THE
COLLABORATIVE INFLUENCA VACCINE
INNOVATION CENTER IS KNOWN AS
THE CIVICS HAD PRECLINICAL
STUDIES ON A NEW VACCINE THAT
OUR CIVICS INVESTIGATORS
DESIGNED USED TO TARGET THE
HHSTOCK AND FOUND THIS
EXPERIMENTAL VACCINE PRODUCED A
STRONGER RESPONSE, AND IT WAS IN
TRANSLATIONAL MEDICINE JUST A
FEW WEEKS AGO, NEXT SLIDE,
PLEASE.
SO, SO I THINK IN A PAST MEETING
I ASKED FOR APPROVAL FOR FISCAL
YEAR 25, SBIR CONTRACT TOPIC AND
WE HAVE 1 ADDITIONAL CONTRACT
TOPIC TO ASK FOR YOUR
CONSIDERATION AND APPROVAL, SO I
WILL DISCUSS THAT NOW.
NEXT SLIDE, PLEASE.
THIS WOULD BE A SOLICITATION TO
CALL FOR DISCOVERY AND
DEVELOPMENT OF ORAL, SMALL
MOLECULE DIRECT ACTING
ANTIVIRALS THAT TARGET VIRUSES
OF PANDEMIC POTENTIAL, THIS
ADDRESSES A PROGRAM THAT WE HAVE
CALLED THE ANTIVIRALS FOR
PANDEMIC PROGRAM, THIS IS THIS
IS--WE RECOGNIZE IT WAS VERY, WE
WERE SLOW TO DEVELOP NEW SMALL
MOLECULE THERAPEUTICS DURING THE
COVID RESPONSE, THE 1S THAT MADE
IT TO AUTHORIZATION AND
LICENSURE REALLY WERE, WERE
REPURPOSED DRUGS SUCH AS
REMDESAVIR AND [INDISCERNIBLE]
AND ALSO THE PROTEASE INHIBITOR
PLAXWELL, OVID, BUT LEADING
THROUGH LEAD OPTICAL IMAGES
MIDDATION, THROUGH PRECLINICAL
TESTS AND PRECLINICAL TRIALS,
THAT ALWAYS JUST TAKES LONGER
THAN WAS THE TIME AVAILABLE FOR
AN EFFECTIVE PANDEMIC RESPONSE,
SO WE'RE TRYING TO MAKE MORE
INVESTMENTS IN IN AREA, WE HAVE
A NUMBER OF DRUG DISCOVERY
CENTERS WHICH ARE WORKING ON
THIS BUT WE NEED TO FILL IN
OTHER GAPS AS WELL AND WE HOPE
THAT THIS SOLICITATION SUCH AS
THIS WILL GET SMALLER GROUPS AND
BOY BIOTECH TO COME IN WITH
THEIR DISCOVERIES.
THE FOCUS IS TO FOCUSED ON
ANTIVIRAL DISCOVERY, ANTIVIRALS
ADMINITTERRED IN THE OUTPATIENT
SETTING, ORALLY OR OTHER
NON-CUTANEOUS ROOTS THAT WOULD
FOCUS ON 1 OR MORE OF THE VIRAL
PATHOGENS WITH FAMILIES AND THIS
WOULD INCLUDE INFLUENZA IN
ADDITION AND CORONA VIRUSES IN
ADDITION TO OTHER VIRUS FAMILIES
THAT WE'VE IDENTIFIED WITH
PANDEMIC POTENTIAL.
SO I WOULD ASK YOU TO VOTE ON
THIS IN YOUR ELECTRONIC COUNCIL
RECORD AND HAPPY TO TAKE ANY
QUESTIONS BEFORE I HAND THE
MICROPHONE OFF TO LAUREN.
OKAY, GOOD EMPLOY.
>> OKAY.
IMRAIT.
OKAY, SO I AM LAUREN, AND I AS
WAS JUST MENTIONED RECENTLY
JOINED NIAID FOR THE PROGRAM
OFFICER FOR CEIRR, SO I WILL
GIVE AN INTRODUCTION INTO THE
PROGRAM AND TALK ABOUT OUR
ACTIVITIES AND RESPONSE TO THE
REENLT HIGHLY PATHOGENIC
INFLUENZA OUTBREAK FROM DAIRY
KALGT.
SO WHEN I SAY CEIRR, IT STANDS
FOR THE CENTERS OF EXCELLENCE
AND INFECT WERE AND RESPONSE.
THIS WAS INITIATED IN 2000
SERVE, AT THE TIME IT HAD AN SOT
END STANDING FOR SURVEILLANCE.
IT WAS ESTABLISHED FOR THE HHS
PANDEMIC INFLUENZA PLAN AND THE
GOAL WAS TO LEVERAGE THE
EXPERTISE OF OUR EXTRAMURAL
INVESTIGATORS TO UNDERSTAND THE
IMPACT OF EPIDEMIC INFLUENZA AND
REDUCE THE THREAT OF PANDEMIC
INFLUENZA.
SO AS I MENTIONED IT WAS
ESTABLISHED IN 2007, THEY ARE 7
YEAR CONTRACKS AND WE'RE IN OUR
THIRD ITERATION NOW WITH SEER.
THE PROGRAM OR THE NETWORK
RATHER IS COMPRISED OF 7
CENTERS, 6 OF THOSE ARE HOUSED
IN ACADEMIC INSTITUTIONS
INCLUDING THE UNIVERSITY OF IMA
GATE KEEPER, IKAN--KANA SCHOOL
OF MEDICINE AT MT. SINAI, EMORY
UNIVERSITY, JOHNS HOPKINS,
UNIVERSITY, UNIVERSITY OF
PENNSYLVANIA AND THE ST. JUDE'S
RESEARCH HOSPITAL.
WE HAVE A SEVENTH CENTER
RESPONSIBLE FOR PROCESSING DATA
APPROXIMATE COMMUNICATION AND
THIS TO HELP WITH DIGITAL
CONFUSION.
SO AS I MENTIONED, THESE ARE
CONTRACT MECHANISMS AND THE
DIFFERENCE HERE INSTEAD OF GRANT
SUPPORT FOR OUR EXTRAMURAL
INVESTIGATORS IS THIS LENDS US A
LEVEL OF AGILITY AND FLEXIBILITY
WHEN WE ARE FACED WITH AN
OUTBREAK SITUATION.
SO WE ARE ABLE TO RAPIDLY
REDIRECT THE EFFORTS OF OUR
SOCIETIES BECAUSE BECAUSE THIS
IS THE FIRST DETECTION OF
INFLUENZA VIRUS IN CATTLE,
NOBODY WAS STUDYING THIS SPACE
BEFORE, SO WITH A REDIRECTION
AND A CHANGE IN A STATEMENT OF
WORK, WE WERE ABLE TO MOVE OUR
SCIENTISTS INTO THIS AREA AND
REALLY GET STARTED ANSWERING
THESE RELEVANT QUESTIONS EARLY
ON.
SO 1 OF THE OTHER ITERATIONS OF
THE CEIRREFRESH YOUR
RECOLLECTION NETWORK IS THE RISK
ASSESSMENT FOCUS, AND WE SET UP
THE RISK ASSESSMENT PIPELINE
KNOWN AS RAP, AND SO THIS IS
DESIGNED OF 4 DIFFERENT FOCUS
AREAS, WHILE IN SURVEILLANCE,
SURVEILLANCE AT THE HUMAN
INTERFACE, COMPUTATIONAL AND N
MODELING AND REGENERATION, AND
THE IDEA IS THAT WE'RE
DECENTRALIZING OUR RISK ARK
ASSESSESMENT EFFORTS SO IT'S NOT
HOUSED IN ANYONE PARTICULAR
CENTER BUT WE HAVE, WOOING
GROUPS WITHIN EACH OF THESE
FOCUS AREAS THAT ARE COMPRISED
OF INVESTIGATORS FROM ALL 7
CENTERS AND THIS IS AN EFFORT TO
REALLY BE MOST EFFICIENT IN
USING OUR RESOURCES AND OUR
EXPERTISE SPREAD ACROSS THE
ENTIRE NETWORK, SO THE
DELIVERABLE, THE ULTIMATE
DELIVERABLE OF THE RISK
ASSESSMENT PIPELINE WOULD BE AN
EXECUTIVE REPORT, SOMEWHAT
SIMILAR AND IN ACCORD NATION
WITH CDC, [INDISCERNIBLE] THAT
DETAILS CEIRR EMERGENT OF THE
STRAIN BUT ALONG THE WAY WE ARE
DELIVERING A LOT OF INFORMATION
TO THE FIELD WITH OUR
CHARACTERIZATION STUDIES AS WELL
AS CHARACTERIZATIONS SHARED
WITHIN THE CEIRR NETWORK AND THE
FIELD AS A WHOLE AND THE WRAP IT
WAS INITIATED IN JANUARY, IT HAD
2 MONTHS TO GET OUR FEET UNDER
US, AND TAKE OFF RUNNING WITH
THE BOVINE OUTBREAK THAT STARTED
IN MARCH.
NOW BEFORE WE GET BACK I JUST
WANT TO DO A LITTLE BACKGROUND
ON THE HIGHLY PATHOGENIC AVIAN
INFLUENZA SO WE'RE ALL ON THE
SAME PAGE.
SO IN 1997, THE FIRST HUMAN CASE
WAS REPORTED AND THIS WAS A
HUMAN WHO HAD DIRECT CONTACT
WITH AN A BIRD, SINCE THEN IT'S
BEEN FAIRLY SPORADIC AND THERE
HAVEN'T BEEN RESULTS OF DIRECT
SUSTAINED HUMAN TO HUMAN
TRANSMISSION, SO IT'S BEEN AGAIN
IMPACT OR CONTACT WITH AN
INFECTED ANIMAL OR VERY CLOSE
CONTACT WITH AN INFECTED
INDIVIDUAL AND HOUSEHOLD.
BUT AS YOU CAN SEE WE HAVE A 10
YEAR TIMELINE AND GETTING
TOWARDS 2020, AND 2021, WE HAVE
REGULAR SPIKES IN ACTIVITY SO
WHAT THE QUESTION IS WHAT IS
DIFFERENT NOW, AND THE ANSWER IS
WE SAW THE ARRIVAL OF CLAYED
2.3.4.4 B, AND SPREAD ACROSS
AFRICA AND ASIA, IN THE
FOLLOWING 2 YEARS THEY CROSSED
NORTH AMERICA AND SOUTH AMERICA
AND RESULT INDEED UNPRECEDENTED
NUMBERS OF DEATHS IN WILD
BITTERS AND OUTBREAKS IN
DOMESTIC POULTRY.
THE OTHER INTERESTING FEATURE
ABOUT THIS PARTICULAR CLAYED IS
THAT WE'RE SEEING MORE AND MORE
SPILL OVER EVENTS TO MAMMALS, SO
WE'RE TALKING ABOUT DAIRYICALITY
TODAY BUT YOU ALL MAY REMEMBER
THE MARINE MAMMAL DIE-OFFS THAT
WERE BEING REPORTED ALONG THE
COAST OF THE SOUTH AMERICA WHERE
WE'RE SEEING H5 POP UP IN
ANIMALS SUCH AS EELS AND
DOLPHINS, WHICH IS COMPLETELY
UNEXECKED.
SINCE 2020 THERE HAVE BEEN 12
HUMAN CASES OF CLAYED 2344 B AND
THAT DOES INCLUDE THE RECENT H5
CASES AFFILIATED WITH THE DAIRY
KALGT OUTBREAK HERE IN THE
UNITED STATES, SO LET'S TALK
ABOUT THE UNITED STATES THEN, SO
AS I MENTIONED, WE DIDN'T HAVE
AN INTRODUCTION OF THE HIGH PATH
244 B H5 N1 UNTIL 2021 AND 2022
AND SINCE THEN WE'VE HAD 48
STATES REPORT POULTRY
INFECTIONS, WE'VE ALSO HAD CLOSE
TO 10,000 CASES DETECTED IN WILD
BIRDS AND WE'VE HAD A TOTAL NOW
OF 4 HUMAN CASES, SO THE FIRST
OF THOSE AS EMILY MENTIONED
OCCURRED IN 2022, ON AN INFECTED
POULTRY FARM, AGAIN THIS WAS A
PERSON WHO WAS IN CLOSE CONTACT
WITH AN AFFECTED BIRD AND THE
FOLLOWING 3 HAVE BEEN AFFILIATED
WITH THE BO VIET OUTBREAK AND
THAT INCLUES CONTACT WITH THE
AFFECTED ANIMALS.
THE USDA PREPORTS HIGHLY
PATHOGENIC IEE, AUDIENCE I HAVE
AN INFLUENZA VIRUS FROM
UNPASTEURIZE MILK FROM
CONSCIENCE CONSCIENCE AND
PARTICULAR TEXT, WE STARRED THE
BALL ROLLING, WE HAD ADDITIONAL
CASES INN FIRMED IN NUCLEOTIDES
MEXICO AND NORTH CAROLINA AND
SOUTH DAKOTA EMPLOY ALSO WITHIN
THAT TIME FRAME CDC RECORDED A
FIRST HUMAN CASE, A DIRY WORKER
FOLLOWING EXPOSURE TO KAGHTS
ACTUALLY PRESENTED WITH SYMPTOMS
OF CONJURCHGHTIVITEIS ONLY.
THEY WERE TREATED WITH
OSLOTAMOVIR AND NO FOLLOW UP
COMPLICATIONS.
OT 24th THE US, DIDA RELEASES
A FERAL ORDER REQUIRING TESTING
OF LACTATING CATTLE OUT OF STATE
AND RESTRICTED MOVEMENT OF
FOLLOWING ANIMAL AND I WILL TALK
ABOUT WHY THAT'S SO SIGNIFICANT.
THE DAY LATER WE GET A CONFIRMED
POSITIVE CASE FROM COLORADO SO
NOW THE STATE COUNT IS UP TO 9
WHICH IS WHERE IT HAS REMAINED
THORS THOSE NUMBERS OF CASES
WITHIN THOSE STATES CONTINUED TO
INCREASE.
ON MAY TENTH THE US, DIDA AND
HHS ANOUNED SUPPORT TO FARMS TO
REDUCE THE BURDEN OF TESTING AND
IMPLEMENTATION OF NEW
BIOSECURITY MEASURES, AND ALSO
THE IMPACT OF H5 N1 CASES AS
THESE FARMERS ARE HAVING TO PULL
THEIR ANIMALS FROM THEIR DAIRY
PRODUCTION LINES.
--LOOKING AT PC R POSITIVE
RETAIL MILK SAMPLES.
ON MAY 22nd THE CDC REPORTS
SECOND HUMAN CASE FOLLOWING
EXPOSURE TO DAIRY CATTLE AND
THEN 2 DAYS LATER THE USDA FOOD
SAFETY INSPECTION SEVENS REPORTS
THAT BY O PARTICLES WERE
DETECTED IN THE MUSCLE TISSUE IN
1 OUT OF 95 THEY TESTED.
AND THEY'RE TALKING ABOUT
COOKING STUDIES WHERE IF YOU
FOLLOW THESE AND COOK THEM TO
THE APPROPRIATE TEMPERATURES YOU
REDUCE OR COMPLETELY ENACT VAIF
ANY VIRUS THAT HAD BEEN
INTRODUCED.
THEN FINALLY LASTED THIS THEY
REPORTED A THIRD HUMAN CASE FOR
DAIRY CATTLE AND THIS 1 IS THAT
THIS INDIVIDUAL IS NOW REPORTING
WITH RESPIRATORY SYMPTOMS AND IN
ADDITION TO CONJUNCTIVE ITIS.
SO HERE IS OUR MAP OF THE
AFFECTED STATES.
AS YOU CAN SEE IT IS STILL 9
THOUGH AS I MENTIONED, WE ARE
STILL AT 69.
ONE HERD WAS AN ALPACA FARM, AND
THIS IS THE FIRST INTRODUCTION
OF THIS VIRUS INTO ALPACAS AS
WELL.
SO I MENTIONED THE FEDERAL ORDER
REDUCING THE TRANSFER OF COW
SAYS ACROSSITATE LINES AND THIS
IS IMPORTANT BECAUSE AS WE'VE
COME TO LEARN, A LOT OF THESE
LARGE DAIRY CONGLOMERATES HAVE
FARMS IN THIS VARIOUS STATES,
THEY HAVE LOCATIONS IN STATES
FOR PARTICULAR PURPOSES.
FOR EXAMPLE, THEY MAY HAVE DRY
LOTS IN ACCIDENT IT TEXT, OR
THEY MAY HAVE PRODUCTION FARMS
IN MICHIGAN OR OHIO SO YOU HAVE
VERY FREQUENT ELECTRONICS MITT
THAT OCCURS BACK AND FORTH SO
1EST MOST COMMON COMPREHENDS YOU
HERE IS THAT YOU HAVE PREGNANT
CATTLE THAT ARE MOVED TO THE
OHIO, THEY ARE ALLOWED TO HAVE
THE CALVES, THEY MOVE DIRECTLY
INTO LACTATION APPROXIMATE AND
MULLK, THE CALVES ARE SHIPPED
BACK TO TEXAS AFTER 4 DAYS OF
BIRTH, TEXAS OR INDIANA.
SO LOTS OF MOVEMENT OF THE HERDS
AND IT'S NOT AN ENTIRE HERD,
IT'S THE UNITS OF HERDS, SO AS
VIROLOGIST WE'RE VERY CONCERNED
HERE, THERE'S A LOT OF MIXING
AND POTENTIAL FOR SPREAD, IF
THESE ANIMALS ARE INFECTED,
THERE HAS BEEN SOME SPILL OVER
COLLECTED, BUT SHOWING UP WITH
NEUROLOGICAL SYMPTOMS ARE
BINDNESS, OUR INVESTIGATORS WERE
ACTUALLY ABLE TO HAVE ACCESS TO
A DECEASED CAT WHERE THEY
PERFORM TD NECROPSY WHERE THEY
FOUND THAT THE CAT WAS
EXPERIENCINGS VIRAL HEMORRHAGIC
PULMONARY EDEMAA.
AGAIN, WE HAVE 3 HUMAN CASES NOW
THAT HAVE BEEN REPORTED ALL WITH
CONJUVENGHTIVITEIS, AND THE MOST
RECENT CASE DOES HAVE
RESPIRATORY, AND THEY WERE
TREATED WITH TAMAVIR, AND IT WAS
GOOD.
SO THAT'S IT AS A WHOLE.
NOW I CAN TALK ABOUT WHAT WE'VE
DONE, WE WERE WELL POSITIONED
WITHIN OUR NETWORK OF VERY LONGS
AND THEIR COLLABORATING
VETERINARIANS TO GET SAMPLES
EARLY ON AND BA THE FOREFRONT OF
SOME OF THIS WORK.
SO AS I MENTIONED WITHIN THE
WRAP, WHAT WE CONSIDER A
STANDARD SET OF VIRAL
CHARACTERIZATION AND RISK
ASSESSMENT ASSAYS SO THIS WILL
BE SAMPLE COLLECTION WITH
SURVEILLANCE GROUPS AND JUST OUR
GENERAL ASIGNIFYS LOOKING AT
BIOCHARACTERRIZATIONS FOR
MAMMALIAN ADAPTATION,
SENSITIVITY TO EXISTING
ANTIVIRALS AND CROSS
PROTECTIVITY, I'M SORRY CROSS
PROTECTIVENESS, CROSS REACTIVITY
OF OUR CURRENT H5
CEIRENVIRONMENTAL STIEBILITY
STUDIES AND REAGENT DEVELOPMENT.
SO WE WERE ABLE TO UNDERTAKE
MANY OF THESE STUDIES ON SITE
VERY QUICKLY BECAUSE WE HAD
THESE CONNECTIONS WITH OUR VETS,
SO FOR EXAMPLE, IN OHIO, WE HAD
EARLY ACCESS TO A FARM, AND WE
WERE ABLE TO COLLECT 900
NAISALLA SWAPS AND INFECT YOWZ
MILK SAMPLES, HOWEVER, AND WE
DID SET UP AN INVESTIGATIONAL
STUDY ON THAT FARM HOWEVER AN
INVESTIGATION WAS NOT ALLOWED ON
SITE DUE TO MEDIA SCRUTINY FROM
PARTICIPATING EARLY ON.
SO THAT HIGHLIGHTS THE ACCESS
ISSUE WE'RE HAVING FOR SAMPLES
THAT EMILY REFERRED TO EARLIER.
BUT WE HAVE OUR 900 SAMPLES
THERE, WE WERE ABLE TO GET
SAMPLES FROM TEXAS, WISCONSIN
AND KANSAS, AND WE WERE APE TO
START OUR RISK ASSESSMENT
STUDIES.
SO I WILL HIGHLIGHT A FEW OF
THOSE NOW, SO THESE FIRST 2 ARE
FROM ST. JUDE CEIRR, AND YOU CAN
READ THESE REPORTS BUT THE FIRST
1 IS TESTING ANTIVIRAL DRUGS
SENSITIVITY AND RESISTANCE AND
THEY LOOKAD BOVINE STRAINS FROM
OHIO AND PARTICULAR TEXT AND
THEY FOUND THEY ARE SUSCEPTIBLE
TO INHIBITORS AND OSELTAMIVIR
AND ZANAMIVIR, AND SUSCEPTIBLE
TO THE CAP DEPENDENT
ENDONUCLEACE INHIBITOR
BALOXAVIR.
SO THESE STUDIES OUR
INVESTIGATORS HAVE CONCLUDED
THAT THE FDA APPROVED ANTIVIRAL
TREATMENTS ARE ALL STILL
APPROPRIATE FOR THE BOVINE
ISOLATES THAT WE'RE GETTING.
WE ALSO COMPLETED TESTING OF H5
CEIRRA WITH THE VACCINE, THIS
DIFFERS BY 6 AMINO ACIDS IN THE
HA PROTEIN BUT IT DOES ILLICIT
CROSS REACTIVE ANTIBODIES TO THE
BOVINE STRAIN TESTED.
SO THE OTHER PART OF OUR
BIOCHARACTERRIZATION STUDIES I
WANT TO HEIGHT LIGHT TODAY COMES
DOWN TO OUR N ANALYSIS AND OUR
COMPUTATIONAL MODELING GROUPS
AND SO AGAIN, THESE ARE ALSO
PUBLISHEDOT SEER WEBSITE AND
THEY THEIR OWN INDIVIDUAL
WEBSITES HOSTING DATA AND I
RECOMMEND CHECKING THEM OUT BUT
THE FIRST IS A NEXT STRAIN BUILD
THAT IS UPDATED REGULARLY WITH
NEW DATA FROM THE USDA WHEN IT'S
RELEASED AND IT CONTAINS,
CANCATANNATED FROM THE OUTBREAK
AND ALSO PROVIDING 1 SEPTORSOT
THAT THERE.
SO THE PURPOSE OF THIS IS TO
UNDERSTAND HOW MUTATIONS ARISE
MAY ADAPT TO MAMMALIAN AX DATA
PROTECTIONATION, SO THIS IS
SPECIFICITY FROM AN AVIAN
SPECIFIC PREFERENCE TO A HUMAN
SPECIFIC PREFERENCE AND SO ON
AND SO FORTH.
ALSO UNDERSTANDING HA STABILITY
AND REACTIVITY AGAINST
POLYCLONAL SERIES POINTSA.
THESE CAN BE FOUND OUR WEBSITE.
SO AS I MEKSED A FEW SLIDES AGO,
WE HAVE A SET OF WHAT WE WOULD
REFER TO AS TRADITIONAL RISK
ASSESSMENT EXPERIMENTS BUT DUE
TO THE NATURE OF THIS OUTBREAK
AND THIS WHOLE FEATURE, WE'VE
HAD TO PULL IN A COUPLE
DIFFERENT EXPERIMENTS TO ANSWER
THESE, THESE ARE INCLUDING KALGT
AND MILK STUDIES.
I WANT TO ADDRESS THE CATTLE
STUDIES TODAY BUT I DO NOT HAVE
DATA TO SHOW YOU BUT THESE ARE
STUDIES BEING DONE IN HIGH
CONTAIN AM SO BSL3 AG
ENVIRONMENTS WHERE THEY'RE
RETROFIT WIDE MILK EQUIPMENT
BECAUSE THESE LACTATING KALGT
HAVE TO BE MILK AT LEAST ONCE A
DAY.
THIS IS A HUGE UNDERTAKING FOR
OUR INVESTIGATORS AS YOU CAN
IMAGINE, AND THE STUDIES ARE
ALL--THE PART OF BEING ONGOING
OR JUST STARTING TODAY AND
THEY'RE IDENTIFYING THE SITE OF
VIRAL REPLICATION, CHARACTERIZED
IN CLINICAL SIZE AND TIMELINE
SHEDDING AND UNDERSTANDING
TRANSMISSION, AND SO THIS
TRANSMISSION PIECE IS
PARTICULARLY IMPORTANT BECAUSE
THIS IS SOMETHING THAT WE STILL
HAVEN'T NAILED DOWN.
IT BECAME FAIRLY CLEAR WITHIN
THE FIRST 2 WEEKS OR SO OF THE
OUTBREAK, WHERE WE'RE SEEING
VIRUS SPREAD VERY RAPIDLY ACROSS
THE MIDWEST, BUT IT'S NOT A
DIRECT INTRODUCTION FROM WILD
BIRTHS TO EACH STATE.
WE'RE SEEING VIRUS FROM TEXAS BE
GENETICALLY IDENTICAL FROM
MICHIGAN AND WE KNOW IT'S BEEN
TRANSFERRED TO THE 2 STATES AND
THAT LED US TO KNOW THAT THERE
IS MOVEMENT WITH THE HEARD BUT
WHAT WE DON'T HUNDRED IS IF
THERE'S COW-COW TRANSMISSION OR
IF WE'RE GETTING DIRECT
MECHANICAL TRANSITION IF YOU
WILL FROM THE MILK PARLORS, SO
WE'RE HOPING TO GET AN ANSWER O
THOSE QUESTIONS WITH THE STUDY
ONGOING AND UNDERSTAND ANY IMP
KAYITIONS TO COW TO KAF FEEDING
OR MILK CONSUCHGZ IF QUEER
GETTING TRANSMISSION THERE AS
WELL.
WE ALSO HAVE AN H5 HA MRNA
VACCINE STUDY, SO HOPEFULLY IT
WILL BE A FEW WEEKS BEFORE WE
GET DATA THERE.
SO I WOULD LIKE TO HIGHLIGHT THE
MILK STUDIES, WHICH IS SOMETHING
THAT ANY VIROLOGIST WOULD SAY,
I'M LOOKING AT RETAIL MILK
EMPLOY BUT WE CATEGORIZED THEM
INTO 2 STUDIES, SO THE IMMEDIATE
QUESTION FOR RAW MILK IS
UNDERSTANDING THE EFFICACY OF
HEAT TREATMENT AND THEN
ACTIVATING THE RIHAVE YOU SEEN
BECAUSE PASTEURIZATION WAS MEANT
TO ADDRESS PACTERIAL
CONTAMINATION, NOT REALLY
CONCERNED ABOUT VIRUS FROM THESE
PARAMETERS WERE ESTABLISHED WE
WOULD ALSO LIKE TO LOOK AT THE
STABILITY OF VIRUSES ON SURVASES
AT AEROSOLS AND AT REFRIGERATED
TEMPERATURES AND THEN ULTIMATELY
LOOK AT IMPLICATIONS OF RAW MILK
INGESTION AND THEN ON THE
PASTEURIZED MILK SIDE, WE WANTED
TO START LOOK BEING AT RETAIL
MILK TESTING AND THAT'S 1 OF THE
FIRST STUDIES WE WERE ABLE TO
COMPLETE.
SO WE HAVE SOME RESEARCHERS,
AGAIN, AFFILIATE WITH OUR SAIPT
JUDE CEIRR CENTER AND WENT ON TO
THE GROCERY STORE AND PURCHASED
150 SAMPLES OF WHOLE MILK ACROSS
THE MIDWESTERN UNITED STATES,
THEY DIDN'T DO THIS IN A RANDOM
WAY, THEY UNDERSTAND BY THE BAR
CODES WHICH PROCESSING PLANTS
AND THE DATES THAT THE MILK WAS
SUPPLIED SO THEY WERE ABLE TO
GET A NICE WIDE BREDTH OF
SAMPLES.
THERE.
SO THEY TESTED APPROXIMATELY 150
SAMPLES, VIA PC R, WITH H5 PROBE
ANDS FOUND THAT 40% WERE
POSITIVE AND THEY THEN SENT
THOSE SAMPLES ON TO SAIPT JUDE
WHO CONFIRMED THAT WITH A
DIFFERENT SET OF H5 PROBES AND
SO NOW WE KNOW WE HAVE RETAIL
MILK THAT IS P, KREBS CYCLE R
POSITIVE FOR INFLUENZA VIRUS SO
THE NEXT QUESTION IS CAN LIVE
VIRUS BE E COVERED OR THEY
ENACTIVATED VIRAL PARTICLES.
SO THEY DID THAT WORK BY PASSING
THE MILK INTO EGGS AND MDCK
CELLS, THEY DID LIVE, AND IT WAS
NOT RECOVERED INDICATING THAT
PASTEURIZATION KILLED THE
BACTERIA, JUST TO BE SURE, THEY
FED THE MICE RAW MILK AND
APPEARS TO BE FINE, SO THESE
ALINE QUITE NICELY WITH WHAT'S
COMING OUT WITH THE FDA AND OUR
COLLABORATORS, OUR INFLUENZA
RESEARCHERS HERE HAVE BEEN
EXTREMELY HELPFUL IN SHARING
RESULTS AND PARAMETERS AND
COLLEAGUES AT THE FDA AS WELL.
SEE THE NEXT POINT WE ARE MOVING
FROM OUR PASTEURIZED MILK TO
TESTING AND WE FOWBD THAT VIRUS
AND MILK HAS A MUCH HIGHER LEVEL
OF CIVILITY THAN VIRUS AND LIKE
PBS WHICH IS INTERESTING AS
WE'RE THINKING ABOUT KIND OF
RISK OF ECPOSURE IN THESE
MILKING PARTNERS, OUR
INVESTIGATORS FOUND THAT VIRUS
AND RAW MILK CO PERSIST ON
RUBBER LINERS AND PLASTIC ON 70%
RELATIVE HUMIDITY FOR WELL OVER
AN HOUR AND WHEN YOU ARE
THINKINGOT GROUND AND YOU'RE
MOVING COWS RAPIDLY IN AND OUT
OF THE MILK PARLOR AS WELL AS
DAIRY WORKERS, THERE'S A LOT OF
LIVE VIRUS JUST HANGING AROUND.
AND AGAIN THIS WORK HAS NOW BEEN
PUBLISHED AS A PREPRINT AND IS
ALSO CAN BE FOUND ON OUR
CEIRR WEBSITE IF YOU ARE
INTERESTED IN LEARNING MORE.
SO THE FINAL PIECE OF WORK I
WOULD LIKE TO HIGHLIGHT, THIS IS
JUST RECENTLY PUBLISHED IN THE
NEW ENGLAND JOURNAL OF MEDICINE
ON PAY 24th, AND THIS IS
PRACTICES A GROUP AFFILIATED
WITH OUR CRYPT CEIRR CENTER
WHICH IS MT. SINAI AND THEY DID
A VARIETY OF MILK STUDIES WITH
RAW MILK.
THE FIRST THING THEY DID WAS
HEAT TREATMENT STUDIES AND THEY
WERE LOOKING AT THE PARAMETERS
FOR 2 MONITOR PASTEURIZATION
METHODS, THIS IS VAT PASTEURIZE
EXPIGZ HIGH TEMPERATURE PASTURE
EYATION, SO THIS EXISTS OF 30
MINUTES AT 63-DEGREES FOR A
LARGE VOLUME OF LIQUID AND THE
OTHERS IS 72-DEGREES CELSIUS FOR
152ndS BUT IT'S A CONTINUOUS
SLOW PASTEURIZATION, AND THIS IS
A SMALL TUBE THAT THE MILK IS
MOVED THROUGH AND THE LIQUID IS
CONSTANTLY MOVING.
SO THAT ASPECT OF IT COULD NOT
BE RECAPITULATED IN THE LAB, THE
ONLY THINK THIS THEY COULD
RECREATE WERE THE TIME AND
TEMPERATURE PARAMETERS.
AND SO THEY FOUND THAT THAT
PASTEURIZATION DOES ENACTIVATE
THE VIRUS FULLY BUT WELL IS
RESIDUAL ACTIVITY DETECTED
FOLLOWING THE HIGH TEMPERATURE
SHORT TIME WHICH AGAIN JUST
INDICATES THAT THE INDUSTRIAL
CONDITIONS, THE CONTINUOUS FLOW,
CONTINUES AND NEEDS TO BE LOOKED
AT, WHICH ARE STUDIES THAT ARE
NOW ONGOING WITH THE USDA ARS.
SO THEY ALSO LOOKED AT VIRUS
STABILITY IN RAW MILK AT
4-DEGREES CELSIUS, BASICALLY
JUST REFREJERATED SAMPLES OVER A
5 WEEK PERIOD AND IT OHM RESULTS
IN ABOUT 1-2 LOG DECLINE OF
VIRUS TITER WHICH OF COURSE HAS
IMPLICATIONS FOR, KIND OF THE
RAW MILK COMSUMPTION MARKET IF
YOU STORE RAW MILK FOR A LONG
TIME, IT'S STILL REMAINS
INFECTIOUS WHICH IS PROBLEMATIC,
THIS IS ANOTHER, WELL, ARE
FURTHER TAKEN ON BY LOOKING AT
ORAL INGESTION, WHERE THEY FED
MICE INFECTIOUS MILK AND THEY
DETERMINED THAT 1-2 DAYS OF
FEEDING, THE MICE ARE DEVELOPING
CLINICAL SYMPTOMS, ALL
EUTHANIZED BY DAY 4 AND THEY
FOUND HIGH TITERS IN THE LUNG,
TRAISHIA AND NAIS AT TURBINATES.
SO THAT WAS A PREY QUICK ROLL IN
TO SOME OF OUR EARLY ACTIVITIES
THERE IS A LOT OF WORK BEING
DONE BUT FOR NOW I'M HAPPY TO
TAKE ANY QUESTIONS.
OKAY.
>> SO WHEN IT SHOWS 40%
POSITIVE, IT'S THE MILK GETS
FULL, DO HAVE YOU ANY IDEA HOW
MANY INDIVIDUAL ANIMALS, HAVE
YOU LOOKED AT INDIVIDUAL
SAMPLES, IS THAT LIKE FROM 1
SUPER SHEDDER OR IS THAT
REFLECTING MULTIPLE INFECTIONS
WITHIN A GROUP?
>> THAT'S A REALLY GREAT
QUESTION AND SOMETHING WE ARE
CURRENTLY TRYING TO UNDERSTAND
HOW BEST TO REPRESENT BECAUSE
YOU'RE ABSOLUTELY RIGHT, THERE'S
A DIFFERENCE FROM A SAMPLE
COMING OFF THE FARM VERSUS
COMING OFF THE STORE.
WE WERE NOT NECESSARILY
INTERESTED IN TRACING THEM
FURTHER THAN THAT.
AGAIN, GETTING IT--THESE ACCESS
ISSUES USDA AND NOT WANTING TO
MAYBE FALSELY IDENTIFY A FARM AS
HAVING FALSE-POSITIVE IF THEY
DON'T BUT IT IS AN EXCELLENT
CONSIDERATION.
BUT THE VIRUS MUST BE IN OTHER
HERDS OR OTHER STATES, ARE YOU
LOOKING IN WASTE WATER, IN TEXAS
THEY'RE DOING THAT BUT IS--
>> YES, SO, CEIRR INVESTIGATORS
ARE NOT CURRENTLY LOOKING IN
WASTE WATER ALTHOUGH WE HAVE THE
SAIBILITY TO DO SO, WE HAVE H5
PROBES WHICH IS SOMETHING THAT I
THINK WE ARE COLLABORATING WITH
CDC ON, CDC IS STARTING THOSE
EFFORTS IN EARNEST AND OF COURSE
THERE'S WATER SCAN WHICH HAS
BEEN DOING THIS FOR A WHILE.
THEY HAVE EXISTING CAN INFLUENZA
DATA BUT EVERYONE'S MOVING TRS
TRYING TO GET TO H5 SPECIFIC
DATA BUT THE WASTE PAWRT DATA HA
IS COMING OUT IS INTERESTING,
IT'S SHOWING SPIKES IN WILL
KACCTICAL, BUT NOT SHOWN
POSITIVE FOR DAIRY HERD
INFECTION, SO IT'S TRACKING DOWN
AND PARSING OUT WHAT THAT DATA
ACTUALLY MEANS.
WHILE NOT HAVING ACCESS TO THE
INDIVIDUAL FARM, IT'S AN
EPIDEMIOLOGICAL HURDLE, FOR
SURE.
>> AS THIS BEEN SEEN IN EUROPE.
>> NOT THAT WE ARE AWARE OF YET
AND WE HAVE INVESTIGATORS FROM
EUROPE THAT ARE COLLABORATORS
AND MEMBERS OF THE SERUM NETWORK
JOINING THE CALLS AND THERE ARE
ALSO EXPERIENCING SOME SIMILAR
HESITANCY FOR TESTING THERE, I
THINK MAYBE PEOPLE DON'T WANT TO
KNOW, BUT, YES, THEY ARE FROM
WHAT WE HAVE HEARD FROM THE,
LIKE DAIRY'S AFFILIATED WITH
ACADEMIC CENTERS, THEY'RE NOT
SHOWING ANY HIGH PATH.
>> LAUREN IS SALE OF RAW MILK
STILL ALLOWED IN THE STATES
WHERE THE OUTBREAKS ARE
OCCURRING?
>> YES, THAT'S THE BIG STICKING
POINT AND WHERE WE'RE TRYING TO
PUBLISH THE RAW MILK STUDIES,
THE FDA CAN ONLY CONTROL
INTERSTATE OR CROSS STATE LINES
OF RAW MILK WHICH IS ILLEGAL AND
IT DEPENDS ON THE STATE AND
THEIR LOCAL JURISDICTIONS BUT
MANY OF THEM HAVE THAT RAW MILK
IS LEGAL TO OBTAIN AND CONSUME.
>> THIS IS AN EXAMPLE WHERE WE
TALKED ABOUT COMMUNICATION WAS
BROUGHT UP THIS MORNING AND I
KNOW PROBABLY THE POPULATION
DOESN'T WANT TO BE TOLL THEY
CAN'T DRINK RAW MILK BUT MAYBE
THIS WOULD BE A CASE WHERE YOU
COULD TRY, WHAT ARE THE RIGHT
PEOPLE TO TRY TO EDUCATE PEOPLE
TO NOT DRINK RAW MILK AT THE
MOMENT AT LEAST NI THINK THE
MESSAGING AS GONE OUT AND IT'S
BEEN REITERATED A NUMBER OF
TIMES.
I'VE HEARD THOUGH THAT
SUBSEQUENT TO THESE REPORTS, THE
RAW MILK DRINKERS HAVE ONLY
INCREASED THEIR ENTHUSIASM FOR
THAT TYPE OF MILK.
IT'S PARADOXICAL TO ME BUT
THAT'S WHAT PEOPLE REPORT.
SO, YEAH, IT'S A PROBLEM.
>> [INDISCERNIBLE] GET RID OF
RAW MILK DRINKING H5 N1 DOESN'T
HAVE A CHANCE.
>> YOU HEARD IT SOMEWHAT AKIN TO
CHICKEN POX PARTIES WHERE PEOPLE
ARE ALMOST ASKING FOR ACCESS TO
RAW MILK.
>> I THINK WE HAVE A COMMENT
ONLINE FROM OUR CDC EXOFFICIO
MEMBER, DAN, DO YOU HAVE A
MICROPHONE?
CAN YOU SPEAK UP?
>> YEAH, IT WAS JUST TO THE
COMMENT ON THE WASTE WATER
TESTING THAT WE ARE ACTUALLY
INITIATING H5 SPECIFIC WASTE
WATER TESTING FOR SPECIFIC
LOCATIONS NOW AND THEN WASTE
WATER SCAN LIKE WAS MENTIONED IS
DOING THE H5 TESTING ALREADY,
BUT IT'S--IT IS A BRAVE NEW
WORLD TRYING TO FIGURE OUT HOW
EXACTLY HOW TO DO ALL THE WASTE
WATER TESTING BECAUSE IT DOES
REFLECT A MIX OF DUMPING OF
MILK, POSSIBLE HUMAN INFECTIONS,
BIRDS, ET CETERA, SO THERE'S A
LOT TO BE LEARNED BUT A LOT THAT
CAN BE DONE WITH WASTE FAWRT,
ESPECIALLY AND TESTING GETS VERY
COMPLICATED RIGHT NOW AND TO THE
POINT OF THE RAW MILK DRINKERS
ON YOUR SCORE, EMILLY'S COMMENT,
THERE ARE THOSE ACTIVELY SEEKING
OUT H5 N1 MILK SO THEY CAN GET
THE BENEFICIAL EXPOSURE TO THE
PATHOGENS THERE BECAUSE THEY
BELIEVE THE USE OF UNPASTEURIZED
MILK IS HELPFUL TO THEM.
>> THANK YOU LAUREN.
SO WE WILL MOVE FORWARD ON THE
ARK JEBDA NOW WITH PRESENTING
THE FISCAL YEAR 26 CONCEPTS FOR
COUNCIL CLEARANCE, THESE ARE FOR
NEW INITIATIVES THAT WOULD BE
FUNDED IN NEW YEAR 26.
OUR FIRST PRESENTER IS NANCY
ERNST, WHO IS THE PROFESSOR OF
COLLEGE AT DMID.
>> YES, THANK YOU.
IT'S A REALLY HARD PRESENTATION
TO FOLLOW WITH A REALLY BIG
CHANGE OF TOPIC HERE, I'M HERE
TO PRECEPT THE CONCEPT FOR THE
COMBATING ANTIBIOTIC RESISTANT
BACTERIA, INTERDISCIPLINARY
RESEARCH UNITS WHAT I WILLY
REFER TO KNOWN AS AS THE
CARBAROOs.
SO THIS CONCEPT IS TO SUPPORT
MULTIDISCIPLINARY RESEARCH
CENTERS FOCUSED ON DISCOVERY TO
EARLY DEVELOPMENT RESEARCH, TO
INFORM NEW APPROACHES TO PREVENT
DIAGNOSE AND TREAT ANTIBIOTIC
RESISTANT INFECTIONS.
AND SO THIS IS A NEW INITIATIVE,
BUT IT BUILDS ON A PREVIOUS
PROGRAM AND IT'S NEW BECAUSE
WE'RE CHANGING FROM A
COOPERATIVE AGREEMENT MECHANISM
TO A PO1 MECHANISM NOW I SHOULD
NOTE THAT BOTH OF THESE
MECHANISMS ARE SIMILAR IN
STRUCTURE, THEY'RE BOTH
MULTIPROJECT AND
MULTIDISCIPLINARY AND THEY
PROMOTE SYNERGY AMONG THE
PROJECTS AND INCLUDE
INVESTIGATIONS WITH DIVERSE SETS
OF EXPERTISE.
THIS CHANGE ALLOWS FOR
MAINTAINING A MULTIDISCIPLINARY
STRUCTURE, WHILE NOT BEING
OVERLY ADMINISTRATIVELY CUM
BUYERSOME EMPLOY SO WE
ANTICIPATE 4-5 ARK WARDS WITH
THE 50 YEAR COST OF $10 MILLION.
SO I PROBABLY DON'T HAVE TO TELL
YOU THAT ANTIBIOTIC RESISTANCE
IS A GROWING PUBLIC HEALTH
THREAT.
IN 2022, A GROUP OF
INTERNATIONAL INVESTIGATORS
REPORTED THE--1 OF THE MOST
COMPREHENSIVE ESTIMATES OF THE
GLOBE AT BURDEN OF ANTIBIOTIC
RESISTANCE TO DATE.
AND THEY ESTIMATED THAT THE
DEATHS ATTRIBUTABLE TO RESISTANT
BACTERIA WERE NEARLY EQUAL TO
THOSE FROM HIV AND MALARIA
COMBINED.
AND THE GRAPH ON THIS SLIDE
SHOWS THE TOP 2 BACTERIAL
PATHOGENS THAT ARE EITHER
ATTRIBUTABLE TOO OR ASSOCIATED
WITH THAT THIS DUE TO ANTIBIOTIC
RESISTANCE.
SO AS I SAID, THE CARBAROOs,
HAD AN EARLIER PROGRAM, IT WAS
SPHEABED IN 2021, WITH 2 CENTERS
BEING ADDED IN 2022, AND THE
CURRENT CENTERS ARE SHOWN HERE
ON THE SLIDE.
YOU CANEE THEY COVER A BROAD
SCOPE OF AREAS ON THE LEFT WE
HAVE 2 CENTERS THAT ARE FOCUSED
ON NOVEL AND NONANTIBIOTIC
APPROACHES.
THESE INCLUDE TWEPMENT OF
RECEPTOR ANALOGUES AND
MONOCLONAL ANTIBODIES TO PREVENT
PATHOGEN COLONIZATION AND
INFECTION AS WELL AS DEVELOPMENT
OF NEW NOVEL COMPOUNDS.
THEY ALSO INCLUDE IDENTIFICATION
OF UNIQUE PHAGE AND DEFINED
BACTERIAL CONSORTIA, TO PREVENT
AND TREAT INFECTION ANDS
RESISTANT INFECTIONS AT MUCOSAL
SITES.
SO THE HARVARD CARBIRU IS
FOCUSED ON ANTIBIOTIC TARGETS IN
GRAM NEGATIVE AND POSITIVE
BACTERIA AND THE 2 CENTERS ON
THE BOTTOM RIGHT ARE FOCUSED ON
MECHANISMS OF RESISTANCE AND
THEIR ASSOCIATION WITH
ANTIBIOTIC TREATMENT FAILURE AND
I SHOULD NOTE THAT THESE CENTERS
ARE NOT FOCUSED ON TRADITIONAL
MECHANISMS OF RESISTANCE BUT ON
TRANSIENT OR PHENOTYPIC,
TRANSIENT OR PHENOTYPIC CELL
STATES SUCH AS PERSISTENCE,
HETEROPERSISTENCE OR TOLERANCE.
SO AS I MENTIONED, AND AS YOU
SEE, THESE CENTERS COVER A
DIVERSITY OF POPPICS BUT IT'S
BEEN REWARDING THAT WITH THESE
CENTERS, AFTER COMING TOGETHER
IN THIS PROGRAM, HAVE FORMED
COLLABORATIONS AND ARE SHARING
TECHNOLOGIES BETWEEN THE CENTERS
SO IT'S REALLY BEEN AN ADMIN
RECORDS AND ADDED VALUE BY
BRINGING THEM TOGETHER.
SO NIAID SUPPORTS A NUMBER OF
PROGRAMS FOR ANTIBIOTIC
RESISTANCE THROUGH THE RESEARCH
PIPELINE AND A FEW OF THEM ARE
ON THIS SLIDE, THE CARBIRUs AS
I SAID ARE ON THE FUNDAMENTAL
EARLY RESEARCH TRANSLATIONAL
STUDIES.
WE ALSO HAVE VARIOUS RFAs FROM
TIME TO TIME FOR PATHOIEN OR
SPECIFIC AREAS, OUR CENTERS OF
EXCELLENCE FOR TRANSLATIONAL
RESEARCH, ARE FOCUSED MORE ON
TRANSLATIONAL DEVELOPMENT AND WE
ALSO HAVE OUR PRECLINICAL
SERVICES AND OUR CONTRACTS FOR
DEVELOPMENT OF MEDICAL
COUNTERMEASURES.
WE ALSO HAVE OUR ANTIBIOTICS
RESISTANCE LEADERSHIP GROUP
WHICH IS NAID'S CLINICAL
RESEARCH NETWORK FOR ANTIBIOTIC
RESISTANCE RESEARCH.
SO THE CARBIRUs HAVE BEEN IN
EXISTENCE FOR A COUPLE YEARS BUT
THEY HAVE A FEW NOTABLE
ACCOMPLISHMENTS ON THIS SLIDE.
THE FIRST IS GOING TO BE
ANTIBIOTICS, NOVEL ZOSURABALPIN
AND IT KILLS DRUG RESISTANCE
A.BAUMANNII, AND THEY
IEE, AUDIENCE DENTIFIED THAT IT
HAS A UNIQUE MECHANISM OF
ACTION, DIFFERENT THAN OTHER
ANTIBIOTICS THAT ARE KNOWN AND
THAT IT INHIBITS A COMPLEXOT
INNER MEMBRANE OF THE BACTERIA
THAT'S INVOFFED IN LPS TRANSPORT
THAT LEADS TO THE BUILD UP OF
TOXIC LEVELS OF LPS AND CELL
DEATH.
THE WASHINGTON UNIVERSITY
CARBIRU INVESTIGATORS STUDIED
GRAM-NEG5 PATHOIENS.
THE EMORY CARBIRU, HAS SHOWN
THAT HETERORESISTANCE WHICH HAS
I SAID IS 1 OF THESE TRANSIENT
MECHANISMS OF ANTIBIOTIC
RESISTANCE, COULD CONTRIBUTE TO
ANTIBIOTIC TREATMENT FAILURE
THAT'S BEEN OBSERVED WHICH IS A
NEW ANTIBIOTIC THAT HAS HAD SOME
CONFLICTING SUCCESS IN THE
CLINIC.
AND RECENT DATA SHOWS THAT MAY
BE DUE TO AMPLIFICATION OF
OTHERWISE INEFFECTIVE BETA
LACKED BASIS IN THE CELLS.
THE DISCOVERY OF THE NOVEL PHAGE
DESTROYS PSEUDOMOMAS AERAGIROSA
BIOFILMS SINNEST GISTIC WITH
ANTIBIOTICS.
WE ALLUDED TO IT WOULD BE
FUNCTIONAL CHARACTERIZATION AND
BOTH BACTERIAL HOST FACTOR IS
IMPORTANT IN INFECTION AND
RESISTANCE.
STUDIES TO IMPROVE OUR
UNDERSTANDING OF THE GENETIC AND
PHENOTYPIC MECHANISMS OF
RESIEVANCE AND THE ROLE IN
ANTIBIOTIC TREATMENT FAILURE,
THE DISCOVERY AND VALDATION OF
EARLY DRUG TARGETS AND
SCREENING.
CHARACTERIZATION AND VALIDATION
OF NOVEL ANTIBOTTICS AND
NONANTIBIOTICS PRODUCTS AS WELL
AS STUDIES TO IMPROVE OUR
UNDERSTANDING OF THE HOST
RESPONSE TO ELIM NAT INFECTION
AND UNDERSTAND HOW ORGANISMS
EVADE THE IMMUNE RESPONSES.
WE'RE ALSO INTERESTED IN STUDIES
ON HUMAN ASSOCIATED MICROBIAL
COMMUNITIES AND THE ROLE THEY
PLAY IN SUSCEPTIBILITY AND
RESISTANT TO INFECTIONS, AS WELL
AS THE SYSTEM LEVEL USE OF
APPROACHES TO IDENTIFY HOST AND
BACTERIAL INTERACTIONS IMPORTANT
FOR INFECTION AND RESISTANCE.
SO THE CARBIRUs WILL FOLK US
ONED TOP GLOBAL ANTIBIOTIC
RESISTANT PATHOIENS PLUS CDC
URGENT THREATS AS LOS ANGELESED
HERE, THESE WOULD BE THE
CARBAPENTINE REGIMEN UMKC
RESISTANCE AND AND KR, MDR
PSEUDOMONAS AERUGINOSA, DRUG
RESISTANT GONORRHOEAE,
METHICILLIN-RESISTANT STAFFY LO
COCCUS AURUOUS, AND VAINK O
MICEIN-RESISTANT ENTHUSIASMER O
OKRRK COCCI, AND DRUG RESISTANT
STREPT O CAUCUS, AND OVER ALL
THEY WERE SUPPORTIVE OF THE
PROGRAM AND ENTHUSIASTIC AND I
HOPE I CAPTURED THEIR COMMENTS
PROARPLY HERE, I WELCOME ANY OF
YOU TO CORRECT ME IF I'M WRONG.
THE BROAD SCOPE OF THE THE
PROGRAM WAS NOTED BUT I HOPE I
TOLD YOU IN MY PRESENTATION HOW
THAT'S BEEN SOMEWHAT
ADVANTAGEOUS.
THEY ALSO NOTED TO INSURE THAT
PROJECTS ARE MULTIDISCIPLINARY
AND SINNER GESTIC.
AND I WAS ASKED TO KIND OF
MODIFY THE HOST RESPONSE COPE
THAT WE HAD INITIALLY INCLUDED
AND I DID THAT IN THE
PRESENTATION THAT I PRESENTED.
AND SO WITH THAT, I'LL TAKE ANY
QUESTIONS.
>> ANY QUESTIONS FROM COUNCIL
MEMBERS ON THE CARBIRU IN
GENERAL OR JUST COMMENTS?
>> GUESS THAT H5 M1 PRESENTATION
GOT EVERYBODY SOBER.
NTHANK YOU NANCY.
>> THANKS.
>> SO OUR FIRST 3 CONCEPT
PROPOSALS ARE IN THE BUNDLE OF
ANTIBACTERIAL RESISTANCE AND THE
NEXT PRESENTER IS JEREMY STARR,
WHO IS ONLINE.
JEREMY WILL TALK ABOUT--HE'S IN
THE DRUG QUEPMENT CENTER OR
SECTION OF OBRRTR AND HE WILL
TALK ABOUT CHEMISTRY CENTERS FOR
COMBATING ANTIBIOTIC RESISTANT
BACTERIA, THE CC-FOR CARB.
JEREMY ARE YOU THERE HAD.
>> YES, I'M HERE, CAN YOU HEAR
ME?
>> YES.
>> THANK YOU EMILY, I AM JEREMY
STA, RR, I AM IN THE DRUG
DEVELOPMENT SECTION OF OBRRTR,
AND I WILL TALK ABOUT THE
CHEMISTRY CENTER FOR COMBATING
ANTIBI ATTIC RESIFT ANT
BACTERIA, SO THIS IS A FISCAL
YEAR 26 CONCEPT, OBJECTIVES OF
THIS CONCEPT ARE TO CONTINUE THE
CURRENTLY SUCCESSFUL KRRK C FOR
CARB INITIATIVES SO THIS IS AIAN
CONCEPT IN CONTINUING THE
ORIGINAL CONCEPT, WE PLANNED TO
EXPAND THE CC FOR CARB COMPOUND
COLLECTION WITH ADDITIONAL NOVEL
CHEMO TYPES FOR ANTIBIOTIC
RESIST APT BACTERIA, THE
MECHANISM BY WHICH WE DEVELOPED
NEW LIBRARIES, INVOLVES
COLLABORATING WITH EXTERNAL
RESEARCHERS TO BRING THEIR IDEAS
INTO C C4 CARB, DESIGN NEW
LIBRARIES AROUND THOSE CONCEPTS
AND THEN 60ICIZE THOSE
COMPOUNDS.
THOSE COMPOUNDS ARE THEN
INSERTED INTO THE CC4 CARB
FEBRUARY THE PUBLIC AND PROVIDED
BA BEING TO THOSE COLLABORATORS
ISSUES THE PHYSICAL SAMPLES SO
THEY CAN USE THEM IN THEIR OWN
RESEARCH.
SO 1 OF THOSE OBJECTIVES THAT WE
PROVIDE COMPOUNDS TO EXTERNAL
RESEARCHERS AT STARTING POINTS
FOR THEIR DRUG DISCOVERY
PROGRAMS, THAT'S NOT LIMITED TO
OUR INITIAL COLLABORATORS BUT
ALSO IS OPEN TO PRETTY MUCH
ANYONE WHO HAS A REASONABLE
REQUEST.
ADDITIONALLY, THE CONCEPT
INVOLVES SOME TIER 1 INVITRO
TESTING OF NEW ANTIBACTERIAL
COMPOUNDS PRODUCED BY CC4 CARB
AND THAT GIVES US SORT OF A
COMPLETE PICTURE OF THIS REALLY
CHEMICAL MATTER TAKEN--THEY
WE'RE GENERATING.
SO AS I SAID, THIS IS A RENEWAL
CONCEPT, MECHANISM IS N01 AND WE
INTEND 1 AWARD FROM THIS
CONCEPT.
NEXT SLIDE.
SO THE BACKGROUND, THE SO THE
MAIN DRIVER FOR CC4 CARB IS THE
LACK OF APPROPRIATE CHEMICAL
MATTER FOR DISCOVERING NEW DRUGS
ESPECIALLY FOR GRAM NEGATIVES
BUT GENERALLY FOR ANTIMICROBIAL
RESISTANT BACTERIA.
THE PROBLEM IS ILLUSTRATED FROM
THIS CHART THAT WAS TAKEN FROM
[INDISCERNIBLE] PAPER SHOWING
THE CHEMICAL SPACE HERE ON THE
VIRTUAL MACHINIAL ACCESS, THE
[INDISCERNIBLE] ON THE X-AXIS,
MOLECULAR WEIGHT SO THE CHEMICAL
SPACE OF ALL DRUGS AND MOST
CHEMICAL MATTER YOU MIGHT FIND
IN A CORPORATE KREENING LIBRARY
IS SHOWN, AND THE PATCH OF GRAY
POINTS REPRESENTS WHERE TYPICAL
CHEMICAL MATTER FALLS, HOWEVER
THE COLORED POINTS WHICH HERE
REPRESENT PSEUDOMOAN ISOTOPE
ACTIVE COMPOUNDS, FALL WELL
OUTSIDE OF THAT CLUSTER,
COMPOUNDS, AND THERE ARE MANY
OTHER EXAMPLES WHERE THIS HAS
BEEN ILTRAITED WHERE GRAM
NEGATIVE ESPECIALLY ARE JUST IN
A DIFFERENT CHEMICAL SPACE THAN
WHERE YOU TYPICALLY LOOK FOR
DRUGS FOR OTHER HUMAN TARGETS.
CONSEQUENTLY WHEN SAY IN THE
PHARMACEUTICAL INDUSTRY AND NIEW
ANTIBACTERIAL PROGRAM IS
STARTED, THE SCREENING PROCESS
IS SKEWED AWAY FROM THE KIND OF
CHEMICAL MATTER THAT WOULD BE
ACTIVE AGAINST THESE AGENTS
BECAUSE IT OFTEN DERIVED FROM
THE RESIDUAL CHEMICAL MATTER
FROM OTHER PROGRAMS TARGETING
HUMAN TARGETS.
SO THIS PROBLEM IS WELL KNOWN,
IT WAS IDENTIFIED YEARS AGO NOW
AND WAS PART OF THE BASIS FOR
THE ORIGINAL CONCEPT THAT WAS
APPROVED FOR CC4 CARB, AND THAT
BOILS DOWN TO THEIR BEING
CORPORATE KREENING LIBRARIES
THAT LOOK LIKE TYPICAL TRUGS AND
A LACK OF CHEMICAL LIBRARIES,
ESPECIALLY FOR GRAM NEGATIVE
TARGETS AND O THIS IS A NEED TO
BUILD TAYLORED CHEMICAL MATTER
FOR ANTIBACTERIAL DISCOVERY
ESPECIALLY GRAM NEGATIVES, THIS
IS IDENTIFIED IN A NUMBER OF
PLACES NODABLY HERE IN THE
SCIENTIFIC ROADMAP WHERE THESE
SPECIFICALLY CALLED OUT THE NEED
TO PROACTIVELY SYNTHESIZE NEW
CHEMICAL LIBRARIES WITH GRAM
NEGATIVE TYPE PHYSICAL CHEMICAL
PROPERTIES, AND THAT IS
FUNDAMENTALLY THE PURPOSE FOR
CC4 CARB, NEXT SLIDE.
SO AS I SAID CC4 CARB HAS
EXISTED AS AN ACTIVE CONTRACT
SINCE 2021.
SO WE HAVE KEY ACCOMPMENTS TO
TALK ABOUT.
AS OF FEBRUARY OF THIS YEAR WE
MATE 2571 COMPOUNDS ACROSS 35
DIVERSE SCAFFOLDS, AND AS OF
THIS YEAR, THERE WERE 1800 AND
THEY THEY HAD BEEN TESTED IN ANN
SILLARY TEST ORDER FOR MIC
TESTING AND EVEN THOUGH MIC
TESTING IS NOT INCLUED IN THE
ORIGINAL CONCEPT, WE BOLTED IT
ON THROUGH PRECLINICAL SERVICES
THAT BECAME EARLY IN THE PROGRAM
BECAME OBVIOUS THAT WE NEEDED TO
HAVE SOME DATA ON ALL THE
COMPOUNDS WE MADE SO WE
UNDERSTOOD THE VALUE OF THE
THINGS WE'RE MAKING AND WE COULD
CROSS COMPARE THE VARIOUS
CHEMICAL LIBRARIES THAT WE'RE
MAKING WITHIN THE COLLECTION FOR
CARB.
AS A RESULT BECAUSE WE--WE--YOU
DOING TESTING WE HAVE ALREADY
IDENTIFIED APPROXIMATELY 20
LIBRARIES NOW THAT HAD NEW
UNEXPECTED GRAM NEGATIVE
ACTIVITY OF VARIOUS TYPES AND
THROUGH OUR OUTREACH EFFORTS WE
HAVE HAD ENGAGEMENT WITH OVER 50
EXTERNAL RESEARCHERS AROUND THE
WORLD.
THROUGH OUR OUTREACH, THERE HAVE
BEEN 3 PATENT APPLICATIONS
FILED, 4 MANUSCRIPTS IN
PREPARATION OR 6 NEW RESEARCH
GRANTS THAT WERE SUPPORTED BY
DATA OR INTERACTIONS.
SO ON THE RIGHT, YOU CAN SEE A
MAP OF THE WORLD WITH SORT OF
COLOR HEAT MAP OF WHERE WE HAVE
INTEREST.
SO WE SEE INTEREST IN OUR
WEBSITES GLOBALLY, PARTICULARLY
IN THE U.S. OF COURSE, BUT IN
EUROPE, AND ASIA AND PRETTY
MUCHIN'RE EVERY CONINENT.
WE DO HAVE A WEBSITE.
THE WEB ADDRESS IS SHOWN BELOW
THE MAP AND WE ALSO GENERATED
THE STATEMENT IN A FEW OTHER
WAYS THAT PI, THE CURRENT CC4
CARB IS PRESENTED WILD AMR
CONGRESS IN 2023, ALSO THE 2024
MANUFACTURES CONFERENCE AND
THERE IS A GUARD PIECE SEMINAR
DISCUSSING CC4 CARB IN SOME
DETAIL WHICH YOU CAN WATCH ON
YouTUBE AT THE LINK AT THE
BOTTOM.
NEXT SLIDE.
SO THE SCOPE OF SUPPORT FOR THE
FY26 CONCEPT IS SHOWN HERE ON
THIS SLIDE.
I'LL POINT OUT A FEW THINGS THAT
HAVE CHANGED FROM THE PREVIOUS
CONCEPT AS I GO THROUGH THE
BULLET POINTS.
SO THIS IS A COMPLEX CONTRACT
WITH SEVERAL MOVING PARTS
DIVIDED INTO 4 CATEGORIES OF
PERFORMANCE, SO THE FIRST 1 IS
LIBRARY DESIGN AND LIBRARY
DESIGN ITSELF INVOLVES MULTIPLE
FUNCTIONS THE FIRST 1 IS
OUTREACH SO THIS IS A PRETTY
SIGNIFICANT OUTREACH FOR
COLLABORATORS AND BRING THEM IN
FROM ALL OVER THE WORLD AND
BRING THEM IN FROM THE
ANTIBACTERIAL RESEARCH
COMMUNITY, THOSE ARE REVIEWED BY
THE CONTRACTOR WHICH IS OUR TI,
ALSO BY A SCIENTIFIC ADVISORY
BOARD, THOSIFY KEY OPINION
LEADERS IN THE WORLD, AND
THEY'RE ALSO REVIEWED BY NIAID
PROGRAM OFFICERS, PARTICULARLY
MYSELF.
IN ARK DITION TO THOSE ELEMENTS,
LIBRARY DESIGN COMPONENT
INVOLVES AN 18 MONTH EMBARGO
PERIOD FOR INTELLECTUAL
PROPERTY, SO THIS IS--THIS IS
NEW, THIS IS NOT PART OF THE
ORIGINAL CONCEPTS, AS A POINT OF
CONTRAST WHEN THIS IS ORIGINALLY
PROPOSED ABOUT 5 YEARS AGO, THE
BELIEF WAS THAT WE WERE
OPERATING PRETTY COMPETITIVELY
AND THERE WOULD BE NO NEED TO
HAVE ANY INTELLECTUAL PROPERTY
PROVISIONS WITH ANY CHEMICAL
MATTER AT THIS STAGE OF
DEVELOPMENT.
UNFORTUNATELY THAT BECAME A
NONSTARTER WHEN WE GOT THE
CONTRACT UP AND RUNNING AND
STARTED ENGAGING COLLABORATORS
NOBODY TO WORK WITH US IF THERE
WERE NO INTELLECTUAL PROPERTY
PROTECTIONS EVEN AT THE VERY
EARLY STAGE OF CHEMICAL MATTER
THAT WE'RE CONTEMPLATING.
SO AS I RESULT WE DID IMPLEMENT
AN 18 MONTH EMBARGO PERIOD, THIS
INVOLVES PROTECTING THE PRIVACY
OF THE NEW IDEAS THAT WERE
DISCUSSING WITH COLLABORATORS OR
AN 18 MONTH PERIOD AFTER WHICH
IT DOES THE COMPOUNDS AND
SAMPLES ARE MADE AVAILABLE TO
THE PUBLIC BUT DURING THAT TIME
THAT ALLOWS FOR THE IDEA
ORIGINATOR TO DO WHATEVER PATENT
FILES OR OTHER INTELLECTUAL
PROPERTY PROTECTING MECH INFORM
THEY WOULD LIKE TO IMPLEMENT.
ONCE WE PUT THAT IN PLACE, WE
HAD VERY LITTLE TROUBLE
CONVINCING COLLABORATORS TO WORK
WITH US AND THAT WAS A VERY NICE
SOLUTION SO WE DO PLAN TO
INCLUDE IT FROM THE START IN THE
NEW CONCEPTS FOR THE
CONTINUATION OF CC4 CARB.
OBVIOUSLY IT BEING LIBRARY
DESIGN, DESIGNING COMPOUND
LIBRARIES IS A KEY FUNCTION ONCE
WE'VE GOTTEN THROUGH THE HURDLE,
OF ENGAGING COLLABORATORS HAVING
IDEAS REVIEWED, THOSE IDEAS DO
BECOME COMPOUND LIBRARIES THAT
ARE DESIGNED BY RTI IN
COLLABORATION WITH THE
COLLABORATORS.
OUR GOAL WITH THIS CONCEPT IS 50
NEW DESIGNS OVER 5 YEARS PERIOD.
THAT'S JUST 1 OF THE FUNCTIONS,
ANOTHER FUNCTION EVEN THOUGH IT
HAS 2 2 BULLETS EVEN THOUGH ITS
MOST OF THE LABOR INVOLVED IS
THE COMPOUND SYNTHESIS, SO
THAT'S THE LIBRARY HAVING
BETWEEN 50 AND 300 COMPOUNDS IN
IT, AND ALL THESE COMPOUNDS HAVE
TO KNOW SYNTHESIZED
CHARACTERIZED IN SOME CASES,
CHEMISTRY WORK HAS TO BE DONE TO
OPTIMIZE ROUTES TO ENABLE ACCESS
TO THE DESIGN COMPOUNDS, SO
THERE'S AN EXTENSIVE AMOUNT OF
CHEMISTRY LABOR GOING ON AT RTI
FOR DELIVERING THESE COMPOUNDS.
OUR GOAL WITH THE NEW CONCEPT IS
10,000 COMPOUNDS, TO GO OVER THE
5 YEAR PERFORMANCE PERIOD.
SO I MENTIONED COMPOUND TESTING
WAS NOT PART OF THE ORIGINAL
CONCEPT ABOUT 5 YEARS AGO AND
THAT WE ARE CURRENTLY DOING IT
THROUGH PRECLINICAL SERVICES.
IT'S BEEN QUITE SUCCESSFUL IN
MANY WAYS AND SO, WE WANT IT TO
BE AN INTEGRAL PART OF CC4 CARB
GOING FORWARD, SO IN THE NEW
CONCEPT WE ADDED IT AS A KEY
FUNCTION, SOPHISTICATED WE WILL
CONDUCT TIER 1 INVITRO TESTING
ON ALL COMPOUNDS.
IN ADDITION THORS THOSE 3
FUNCTIONS WHENEVER YOU'RE
GENERATING PHYSICAL SAMPLES OF
CHEMICAL MATTER, YOU HAVE TO
MANAGE THOSE SAMPLES, TAKE CARE
OF THEM, STORE THEM CORRECTLY,
ALSO ARRANGE FOR DELIVERY OF THE
SAMPLES TO TESTING ASSAYS AND TO
REQUESTERS WHO WANT TO USE THEM
IN THEIR OWN TESTING ASSAYS.
SO WE HAVE A COMPOUND MANAGEMENT
FUNCTION THAT WILL TORE AND
MAINTAIN THE COMPOUND COLLECTION
AS WELL AS MANAGE THE GRIEWKS
SAMPLES TO REQUESTERS.
NEXT SLIDE.
SO THE SCOPE OF SUPPORT WAS IN
TEXT FORM IN THE PREVIOUS SLIDE
AND THE SLIDE I'M SHOWING IT IN
THE MORE SCHEMATIC FORM, THIS IS
HOW CC4 CARB WORKS, ACROSS THE
TOP LINE YOU HAVE THE LIBRARY
DESIGN FUNCTION WHERE THE
APPLICANT OR THE COLLABORATOR
BRINGS AN IDEA TO CC4 CARB,
OFTEN IN RESPONSE TO DIRECT
CONTACT WITH BRUCE OR SOMEBODY
FROM RTI WHO'S ACTING AS A
LIAISON BETWEEN CC4 CARB AND YOU
KNOW IS PART OF THE OUTREACH
PROGRAM.
SO THE APPLICANT BRENGS THE IDEA
INTO THE RTI AND UNDERGOES
ADMINISTRATOR REVIEW FOLLOWED BY
SCIENTIFIC ADVISORY BOARD OR
REVIEW AND THEN IF IT PASSES
THOSE REVIEWS IT GOES INTO
LIBRARY DESIGN.
WHERE THE COMPOUNDS ARE DESIGNED
TO BE PART OF THAT LIBRARY.
AFTER THE COMPOUNDS ARE DESIGNED
IT GOES TO NAID FOR REVIEW SO
EVERY DISCREET COMPOUND THAT
GOES INTO THE COLLECTION IS
REVIEWED AND APPROVED BY NIAID
FOR ITS SYNTHESIZED.
ONCE THAT HAPPENS, I LPC R POR
THE LIBRARY DESIGN GOES INTO THE
SYNTHESIS CUE.
IT'S EVENTUALLY SYNTHESIZED AND
THOSE SAMPLES ARE DIVIDED INTO
MATERIAL THAT GOES INTO COMPOUND
MANAGEMENT, ALONG THE BOTTOM ROW
WHICH WILL SUPPLY PUBLIC
REQUESTS OR IT GOES BACK TO AND
PART TELEVISION GOES BACK TO THE
APPLICANTS SO THAT THEY CAN DO
THEIR OWN TESTING AND USE IT FOR
THEIR OWN PRODUCT DEVELOPMENT.
WHAT'S NOT SHOWN IN THIS
SCHEMATIC IS THAT A THIRD
DIVISION WILL GO OFF TO TIER 1
INVITRO TESTING AFTER COMPOUND
SYNTHESIS UNDER THE NEW CONCEPT.
NEXT SLIDE.
SOPHISTICATED I HAVE MET WITH
COUNCIL MEMBERS
DR. [INDISCERNIBLE] AND
DR. KD--SALLY THEY WERE STROJLY
SUPPORTIVE WITH THE CONCEPT,
THEY DID PROVIDE VERY USEFUL
FEEDBACK, 1 IS TO REMIND ME OR
ASK ME ABOUT WHETHER LIBRARY
PLANS COULD CONSIDER MODALITIES
SIMPLY BEYOND DIRECTING
MATERIALS AND THE ANSWER TO THAT
IS ABSOLUTELY YES, AND ANYTHING
THAT ADDRESSES THE BROAD
QUESTION OF ANTIMICROBIAL
RESISTANCE AND LOOKS LIKE A
POTENTIAL PATH FORWARD AGAINST
SOME GRAM NEGATIVE OR OTHER
DIFFICULT BACTERIAL PATHOIEN IS
ON THE TABLE AND BUT SUBJECT TO
THE REVIEW PROCESS THAT I
DESCRIBED.
THEY ASK ME TO EMPHASIZE THE 18
MONTH EMBARGO PERIOD WHICH I
HOPE I CLARIFIED AND THEY
BROUGHT UP AN INTERESTING POINT
WHICH WAS NOT PART OF MY
ORIGINAL PRESENTATION BUT I
THINK IT'S REALLY IMPORTANT TO
NOTE IS THAT 1 OF THE BENEFITS
OF VIEWING THE TIER 1 DATA,
HAVING THE TIER 1 DATA
GENERATION INTEGRATED IN THE CC4
CARB IS THAT IT'S GOING TO BE
VERY CONSIST EPT DATA ACROSS A
LARGE NUMBER OF COMPOUNDS WHICH
IS ENABLING FOR MACHINE LEARN XG
GETS AROUND SOME OF THE
DIFFICULTIES THAT MACHINE
LEARNING APPROACHES RUN INTO
WITH SORT OF RAW DATA COLLECTED
FROM THE OPEN LITERATURE WHERE
ASSAY IS RUN UNDER DIFFERENT
CONDITIONS AND OFTEN THERE'S
SELECTION BIAS AND WHATOOSE
PUBLISHED.
HERE WE WILL HAVE ULTIMATELY A
BODY OF 10 OR 15,000 COMPOUNDS
WITH INVITRO DATA RUN UNDER
EXACTLY THE SAME CONDITIONS AND
ALL OF IT WILL BE REPORTED AND
AVAILABLE FOR US IN THE FUTURE
MACHINE LEARNING EFFORT.
NEXT SLIDE.
SO THIS IS THE END OF MY NEW
SLIDE, I JUST BROUGHT BACK THE
CONCEPT SLIDE AND HAPPY TO
ANSWER ANY QUESTIONS.
THANK YOU.
>> THANK YOU JEREMY.
ANY QUESTIONS FOR JEREMY ON CC4
CARB CONCEPT.
OKAY, JUST REMEMBERING I NEED TO
REMIND YOU THAT YOU DO HAVE TO
VOTE ON THESE IN YOUR
INDEPENDENT COUNCIL BOOK WHETHER
OR NOT, I THINK THERE'S AN
OPPORTUNITY TO WRITE SUGGESTIONS
IN A BOX.
SO AS I MENTIONED WE HAVE A
BUNDLE OF ANTIBACTERIAL
RESISTANT CONCEPTS, DEVELOPING
BETTER ANTIBACTERIAL
COUNTERMEASURES, AND THE NEXT 1
IS CALLED CENTERS FOR
ACCELERATING PHAGE THERAPY TO
COMBAT ESCAPE PATHOGENS AND
KYUNG MOON WILL PRESENT THAT
TODAY.
MAYBE STAND A LITTLE CLOSER TO
THE MICROPHONE.
OR TRY TO PROJECT A LITTLE.
>> OKAY, SO THIS CONCEPT IS FOR
CENTERS FOR ACCELERATING PHAGE
THERAPY TO COMBAT ESKAPE
PATHOIENS AND THE OBLIGATIONS
YECTIVE IS TO ESTABLISH
MULTIDISCIPLINARY COLLABORATIVE
RESEARCH CENTERS FOCUSED ON
DEVELOPING ROBUST ASSAYS AND
TOOLS FOR ADVANCING PHAGE
THERAPY INTO CLINICAL TRIALS.
SO IF THESE ARE NEW, THE FUNDING
MECHANISM IS THE PO1 AND WE
ANTICIPATE AWARDING 2-3 CENTERS
WITH A FIRST YEAR TOTAL COST OF
$6 MILLION.
SO PHAGE THERAPY IS CONSIDERED
AS A LEADING ALTERNATIVE TO
TREAT INFECTIONS DUE TO AR
PATHOIENS.
IT'S NOTABLE BENEFITS ARE IT'S A
PATHOIENS SPECIFIC SO THE
BENEFICIAL MICROBIOME IS
PRESERVED, PREVENTING SECONDARY
INFECTIONS TO CHANGE THE CD, IT
IS KNOWN TO BE SAFE, PRACTICES
REPORTS FROM PREVIOUS STUDIES.
SO BRIEFLY LOOKING AT THE RECENT
DEVELOPMENT IN 2019 NIAID
PUBLISHED A FRAMEWORK AND
EMPHASIZING PAGE THERAPIES
ABILITY TO COMBAT AR BACKERRIA.
BEFORE 2020 VARIOUS STUDIES WERE
MOSTLY CONDUCTED WITHOUT
RANDOMIZATION IN GROUPS OR CASE
STUDIES, SO VERY LITTLE
STATISTICAL DATA WERE COLLECTED.
SO SINCE THEN MULTIPLE RANDOMIZE
CLINICAL TRIALS HAVE BEEN
LAUNCHED TO ADDRESS THE PREVIOUS
LIMITATIONS.
HOWEVER, LARGER STUDIES WERE
NEEDED TO SHOW CLINICAL
EFFICACY.
SO INCLAUDED IN THESE OF THE
TRIALS, WE HAVE 2 NIAID'S
SPONSORED TRIALS.
ARLG'S TRIAL AND [INDISCERNIBLE]
AND ANOTHER 1 TO TREAT SHIgE
LLA INFECTIONS IN HEALTHY ADULTS
AND BOTH STUDIES ENROLLING
SUBSETS.
SO BASIC RESEARCH AT THE BASIC,
TRANSLATIONAL AND CLINICAL
LEVELS HAVE BEEN SUPPORTED BY
VARIOUS NIAID PROGRAMS.
ESPECIALLY SINCE 2014 A FEW
RFAs ALONG WITH THE
PRECLINICAL SERVES HAVE
SUPPORTED TRANSLATIONAL RESEARCH
AS SHOWN IN THIS BOX.
DESPITE THESE EFFORTS, THERE ARE
4 MAJOR SCIENTIFIC GAPS FOR
DEVELOPING ROBUST PHASE PRODUCTS
EMPLOY FIRST WE DON'T HAVE
STANDARDIZED ASSAYS AND TOOLS
WHICH ARE CRUCIAL FOR DESIGNING
CLINICAL TRIALS IN ORDER TO
OBLIGATIONS STAIN, RECREATE
REPRODUCIBLE DATA.
SO 1 EXAMPLE IS BASIC
ACACCEPTIBILITY TEST, THE
CURRENT INVITRO TEST OF THOSE
LED, PHAGES ABILITY, PHAGES
ACTIVITY IN [INDISCERNIBLE] AND
INFECTION SITES.
ALSO WITHOUT A STANDARDIZED
ASSAY, WE GET INCONSISTENT DATA
ACROSS DIFFERENT LABS.
SECOND, WE DON'T HAVE PROPER
INVITRO MODELS FOR PHAGE
RESEARCH.
FOR EXAMPLE, CHRONIC INFECTION
AND MODEL CELL MAKING.
THE CURRENT TESTS ARE MOSTLY
BASED ON HEALTHY ANIMAL MODELS
WITH ACCURATE INDUCTIONS.
WE ALSO DO NOT HAVE NEW MODELS
INCLUDING ORGANOIDS, 2 MONITOR
THE PHASE AND BACTERIA IN
INYEKSS IN IN VIVO AND TO ARK
ASSESSES THE HUMAN RESPONSES
THIRD, WE DON'T HAVE THE
STRATEGIES TO EVALUATE THE PKPD
RELATIONSHIP IN MODELS FOR
PHAGES.
AGAIN, THE CURRENT MODELING
FAILS TO CONSIDER THAT THE PKPD
PHAGES THOSE ARE ALL
CONVENTIONAL ANTIBIOTICS.
OF COURSE, WE DON'T HAVE
[INDISCERNIBLE] ROUTES FOR
DOSAGES IN PHAGES.
THEREFORE MORE ANIMAL STUDIES
ARE REQUIRED TO CHARACTERIZE THE
PHASE DISTRIBUTION AND
CONCENTRATION .
SO HEAR I WANT TO EMPHASIZE 2
THINGS, WOB CONVENTIONAL ASPECT
BIOTICS HAVE FAILED TO FILL
THESE GAPS WHILE PHAGES DO NOT.
THIS HAS AN AMAZING HINDRANCE TO
PEOPLE IN THERAPY AND TESTING IT
VIGOROUSLY.
WITH A PROPER TOOLS AND
RESOURCES, WE CAN DEVELOP PHAGES
AS VIGOROUSLY AS WE DID FOR
ANTIBIOTICS.
TWO, THESE SCIENTIFIC GAPS ARE
HIGHLY EQUALING ACROSS DIFFERENT
FIELDS.
HOWEVER, THE EXISTING PROGRAMS
ARE LIMITED IN THEIR SCOPE AND
EXPERTISE, THEREFORE WE NEED A
MORE COLLABORATIVE WORK.
SO WHAT ARE THE SCIENTIFIC NEEDS
AND OPPORTUNITIES AND WHY WOULD
THIS INITIATIVE BE SUCCESSFUL
NOW.
SO WE NEEDED TO STANDARDIZE
INVITRO METHOD TO ISOLATE AND
DETERMINE PAGES ACTIVITIES
AGAINST TARGETED BACTERIA IN
INFECTION SITES IN DEVELOPING
PROPERTY INVITRO AND IN VIVO
MODELS IS IMPORTANT FOR
CONDUCTING PHAGE TOCKSIBILITY
TEST AND FOR EVALUATING PKPD.
CONDUCTING SYSTEMS
PHARMAICOLOGGIC STUDIES OF
PHAGES TO DELIVER INTO PHAGE
ANDS PRODUCTS.
THIS PROGRAM WILL MEET THESE
NEEDS BY IMPLEMENTING THE
MULTIDISCIPLINARY RESEARCH.
THE OPPORTUNITIES ARE UTILIZING
ASSAYS AND TOOLS IN PRECLINICAL
SERVICES TO HELP OTHER STUDIES
AND IN LEVERAGING IT'S RESOURCES
TO IMPROVE THE EFFICACY AND
QUALITY OF BETA PRODUCTS.
AND THE ULTIMATE OUTCOME WILL BE
ACCELERATING PHAGE PRODUCT
DEVELOPMENT TOWARD ADVANCED
THERAPEUTICS TO FUTURE CLINICAL
STUDIES.
SO WE BELIEVE THE TIME IS RIGHT
FOR THIS INITIATIVE SINCE THERE
IS A GROWING INTEREST FOR PHAGE
THERAPY.
THEREFORE WE NEED TO ENHANCE THE
PHAGE PIPELINE WHICH REQUIRES
DEDICATED AND COORDINATED AND
COLLABORATIVE EFFORTS.
SO AS MENTIONED EARLIER, WE
ANTICIPATE AWARDING 2-3 CENTERS
THAT CAN LEVERAGE THE RESOURCES
WITH DIVERSE EXPERTISE TO
DEVELOP ASSAYS AND TOOLS.
WE ENVISION EACH CENTER
INCLUDING OUR MULTIDISCIPLINARY
TEAM, IN EACH CENTER, IT ALSO
REQUIRED TO HAVE SYNERGISTIC
PROCESS AND TARGETING A LIST TO
1 ESCAPE PATHOIEN AND HAVE TO
HAVE ANNUAL AND MONTHLY MEETING
TO ENHANCE COLLABORATION AMONG
DIFFERENT CENTERS.
THE PROGRAM TRANSLATIONAL
RESEARCH RANGING FROM
[INDISCERNIBLE] TO THE
FOLLOWING, DEVELOPING USER
FRIENDLY AND HIGH THROUGH PUT
ASSAYS AND TOOLS, GENERATING
PROPER INVITRO AND IN VIVO
MODELS FOR PAID RESEARCH,
PERFORMING SYSTEMS OF
PHARMAICOLOGICAL STUDIES TO
EVALUATE PKPD AND TO ASSESS
VALENCEY, ROUTES AND DOSAGES.
UNDERSTANDING THE HUMAN'MUNE
RESPONSE TO IMPROVE PHAGE'S
STABILITY AND MONITORING SAFETY
AND TOXICITY.
WE WILL NOT WORK ON SCIENCE THAT
DOES NOT CONTRIBUTE TO
PRECLINICAL DEVELOP EXPMENT
CLINICAL TRIALS.
SO WE THANK DR. MARY
[INDISCERNIBLE] AND DR. TAYLOR
FOR THEIR COMMENT AND OVERALL,
THEY ARE THE STRONGEST OF THIS
PROGRAM AND CONCERTED IMPORTANT.
THEY ALSO RECOGNIZED THE
SCIENTIFIC NEED FOR THIS PROGRAM
AND MEETING THIS NEED WILL
ULTIMATELY PAVE THE WAY FOR
FUTURE LARGE CLINICAL TRIALS.
THEY SUGGIEST THE PROGRAM
INSURES COLLABORATIVE
INFORMATION IN CENTERS AND HAVE
A SPECIFIC REVIEW PANEL WITH
PHAGE EXPERTISE AND A VOIDS ANY
ONGOING PROGRAM ESPECIALLY WITH
CETRS.
SO IN SUMMARY, THIS IS THE
CONTEXT ESTABLISHED CENTERS FOR
ACCELERATING ADVANCED THERAPY
AND STUDY OF PATHOIENS, WE
ANTICIPATE AWARDING 2-3 CENTERS
THE FIRST YEAR FOR A COST OF 6
NILE VIRUSSION DOLLARS.
SO WITH THAT, THANK YOU FOR YOUR
ATTENTION.
>> THANK YOU KYUNG.
COMMENTS OR QUESTIONS FROM ANY
COUNCIL MEMBERS.
OR ANYBODY ELSE?
WE'RE A LITTLE AHEAD OF
SCHEDULE, WE DIDN'T PUT A BREAK
IN THE AIENDA BUT IF--SHOULD WE
JUST KEEP GOING, DOES ANYBODY
NEED TO KNOW THE RESTROOM I
THINK AND SAY MAYBE EVEN 3:15 OR
3:20 IF WE KEEP OUR CURRENT
PACE.
SO NEXT DISCOVERY DEVELOPMENT OF
NOVEL THERAPEUTICS FOR SELECT
FUNNINGAAL PATHOGENS AND BAOYING
LIU IS GOING TO PRESENT THIS
CONCEPT.
>> THANK YOU FOR THE OPPORTUNITY
TO PRESENT.
>> WE NEED SLIDES.
>> YEAH, PREFERABLY.
THANK YOU.
>> OUR PURPOSE OF THIS CONCEPT
IS TO DORPHY AND DEVELOPMENT OF
NOVEL THERAPEUTICS FOR SELECT
FUNGAL PATHOGENS INCLUDING DRUG
RESISTANCE CANDID A SPACES,
PARTICULARLY CANDIDA AURIS, AND
ASPER GILLUS, COCCIDIOIDES, AND
MUCORALES, AND WE PROPOSE OUR
R21/R33 MECHANISM AND ANTICIPATE
8-10 AWARDS WITH A FIRST YEAR
BUDGET OF 2.4 MILLION EMPLOY
SOME BACKGROUND.
IN THIS FUNGAL INFECTION
ACCOUNTS FOR ALMOST 1 HALF
MILLION DEATHS EVERY YEAR,
INEREDDER TO ADDRESS THIS UNMET
MEDICAL NEED, IN 2019, AND FOR
THE FIRST TIME FUNGI WERE
INCLUDED IN THE CDC, AMR THREAT
LIST ESPECIALLY CANDIDA AURIS
LISTED AS A THREAT.
IN 2022 LED A LIST, AS WELL AS
PERCEIVED PUBLIC HEALTH.
AND LASTLY, IN THE NIAID
BIODEFENSE AND EMERGING
INFECTIOUS DISEASE PATHOGENS,
COCIDIOIDES, MUCORALES AND AMR
WERE ALL INCLUDED.
SO THE SELECT FUNGAL PATHOIEN
FOR THIS INITIATIVE REFLECT THE
CURRENT PRIORITIES AUTHORIZED IN
THE BIO3 DOCUMENTS.
WHAT ABOUT THE ANTIFUNGALS IN
THE CLINICAL SETTING?
CURRENTLY, THERE ARE ONLY 3
MAJOR CLASSES OF ANTIFUNGALS IN
THE TREATMENT OF THE FUNGAL
INFECTIONS, THEY ARE POLINGS FOR
EXAMPLE, AND FOR TYROSEEN B, FOR
EXAMPLE, FLU CONSALIVA--SALIVA,
AND [INDISCERNIBLE] FOR EXAMPLE,
CASPOFUNNINGIN.
BETWEEN 1980 AND 202040 YEARS A
TOTAL OF 40 ANTIFUNGALS APRAWFED
TO THE FDA AND ALL OF THEM
BELONG TO THE SAME EXISTING 3
CLASSES SO THE TREATMENT APGZ IS
EXTREMELY LIMITED.
OVER THE PAST 3 YEARS, 3 NEW
ANTIFUNGALS WERE APPROVED.
AGAIN FLUCONAZOLE, AND WHERE
[INDISCERNIBLE] IS A NUMBER OF
THE NEW MEMBER TO THE FAMILY.
FIRST THERE ARE LIMITED OPGS
CURRENTLY, WE ONLY HAVE 3 MAJOR
CLASSES OF ANTIFUNGALS AND 2 OF
THEM TARGETS GHASTERAL OR
GASTROSYNTHESIS PATHWAY WHICH IS
RELATED TO FUNGAL CELL MEMBRANE
INTEGRITY AND 1 OF THEM TARGETS
FUNGAL CELL WALL GENESIS
PATHWAY, SO THE TARGETS ARE VERY
LIMITED.
EVEN WITH TREATMENT, THE
EFFICACY IS VERY LIMITED SO
OVERALL, IN THIS FUNGAL
INFECTION, IS ABOUT 20%.
AND SECOND, THE TOXICITY, IS
ABUNDANT, [INDISCERNIBLE] MAY BE
FOR TYROSEEN B, THE RENAL
TOXICITY MAKES THE TREATMENT
EXTREMELY CHALLENGING AND THE 4
AZOLE DRUGS, DRUG-DRUG
INTERACTIONS ALSO CONTRIBUTE TO
THE POOR TREATMENT OUTCOME.
AND THIRD, THE EMERGING
RESISTANCE AND PATHOGEN FOR
EXAMPLE, SOME CLINICAL ISOLATES
OF CANDIDA AURIS HAVE BEEN
RESISTANT TO ALL 3 MAJOR CLASSES
OF ANTIFUNGALS.
YOU KNOW IN OTHER WORDS THEY ARE
NO TREATMENT OPTIONS FOR THIS
TYPE OF INFECTION.
AND THE LASTLY, ANTIFUNGAL DRUG
THEMSELVES ALSO HAD MEDICATIONS,
PROSEENS AND THESE DO NOT HAVE
ORAL MEDICATION AND FOR THE
PRELIMINARY CANNED WHAT
INFECTION, THE POOR TARGET
EXPOSURE MAKE THE TREATMENT
EXTREMELY DIFFICULT.
FOR THIS PAPER, I SUMMARIZED
MOST OF THE CURRENT ANTIFUNGAL
IN THE [INDISCERNIBLE] IN THE
CLINICAL SPACE.
OUT OF THESE 7 ANTIFUNGALS, ONLY
KD--SALLY WATRULY FIRST IN CLASS
WITH NOVEL MECHANISM OF ACTION
MOST OF THEM HAVE BROAD SPECTRUM
AND THEY ARE ACTIVE AGAINST
YEAST AS WELL AS MOUSE WITH THE
EXCEPTION OF [INDISCERNIBLE],
AND FROM THE PEOPLE, YOU CAN
ALSO SEE QUITE A NUMBER OF THEM
HAVE ORAL FORMULATION AND SOME
OF THEM HAVE [INDISCERNIBLE]
FORMULATION SO TO SUMMARIZE THE
CURRENT ANTIFUNGAL CLINICAL
PATHWAY CAN PROVIDE A POTENTIAL
BETTER TREATMENT OPTION FOR
FUNGAL INFECTIONS THEY CAN POWER
EXISTENCE, THEY CAN POWER
EXPANDED DRUG DELIVERY OR
APPROACH AND THEY CAN DO A NOVL
MECHANISM OF ACTION.
THE OTHER TOOL INCREASED
LIKELIHOOD OF SUCCESS AND THE
DIVERSITY OF ANTIFUNGAL DRUG
CLUSTERS, WE NEED TO PRIME THE
PIPELINE FROM EARLY PHASE, FROM
THE EARLY DORPHY AND PRECLINICAL
DEVELOPMENT STAGE.
THAT'S EXACTLY WHAT THIS
INITIATIVE IS ABOUT.
SO WHAT THE CONCEPT IS ABOUT.
THIS CONCEPT WILL SUPPORT EARLY
STAGE, ANTIFUNGAL DORPHY AND THE
PRECLINICAL DEVELOPMENT.
SO IDEALLY THE GRADUATES FROM
THIS CONCEPT CAN FIT INTO THE
FUTURE RO-1 APPLICATION, FOR THE
FUNGAL SPECIFIC EAA ALL TREY
PRIVATE SECTOR FOR DEVELOPMENT.
IN TERMS OF SCOPE OF SUPPORT, WE
ARE PROPOSING MOUSE DRIVEN R21,
R33 MECHANISM, A NOVEL
THERAPEUTIC IS DEFIED AT LEAST
[INDISCERNIBLE], IT CAN BE AGENT
WITH A NOVEL MECHANISM OF
ACTION, IT CAN BE AN AGENT
AGAINST A NOVEL, NONTRADITIONAL
TARGET FOR EXAMPLE, MONOCLONAL
ANTIBODY.
IT CAN BE AN AGENT AGAINST A
TRADITIONAL TARGET WITH
SIGNIFICANT IMPROVEMENT ON
[INDISCERNIBLE] AND
DISTRIBUTION.
IT CAN BE AN AGENT THAT CAN
OVERCOME RESISTANCE MECHANISMS
ASSOCIATE WIDE A TRADITIONAL
TARGET.
SO HERE I ALSO GAVE SEVERAL
EXAMPLES FOR SUPPORTED ACTIVITY
INCLUDE BUT NOT LIMITED TOO,
SOMEHOW TARGET IDENTIFICATION,
VALIDATION, HIT TO LEAD, LEAD
OPTIMIZATION, AND EARLY
PRECLINICAL DEVELOPMENT
ACTIVITIES, BUT NOW TO INCLUDE
THE ENABLING STUDIES AND AGAIN
GMP MANUFACTURING.
THOSE ARE VERY EXPENSIVE
ACTIVITIES.
OUR COUNCIL FEEDBACK, I WOULD
LIKE TO THANK DR. PALMER AND
DR. [INDISCERNIBLE] FOR THEIR
TIME AND CONSIDERATION.
BOTH OF THEM STRANG'RE STRONGLY
SUPPORT THIS INITIATIVE, THEY
RECOGNIZE THE NEED TO DISCOVER
AND DEVELOP NOVEL ANTIFUNGAL
THERAPEUTICS AND THE THREAT OF
EMERGING AND ANTIFUNGAL
RESISTANCE.
IN TERMS OF SCOPE, DR. PALMER
ALSO COMMENTED THE DEFINITION OF
NOVEL THERAPEUTICS REFLECTS THE
CURRENT ANTIFUNGAL NEEDS.
DR. [INDISCERNIBLE] HAD A
QUESTION ON WHETHER THE AMOUNT
OF FUNDING IS SUFFICIENT TO R33.
TO ANSWER THAT THE CURRENT
2.4 MILLION IS ONLY FOR THE
FIRST YEAR AND THEN BY THE END
OF YEAR 2, WE ANTICIPATE 50% OF
R21 WE WILL TRANSITION TO R33.
AND LASTLY, AS PALMER SUGGESTED
DURING THE INITIATIVE
DEVELOPMENT STAGE, MAKE IT A
CAREER, THERE WOULD BE NO DIRECT
R33 OPTION SO IN ORDER TO BE
ELIGIBLE FOR THE PROGRAM MATCHED
SUCCESSFULLY ACHIEVE THE
MILESTONE PROPOSED FROM R21.
WITH THAT I CONCLUDE MY
PRESENTATION.
HAPPY TO TAKE ANY QUESTIONS.
>> THANK YOU KYUNG, ANY COMMENTS
OR QUESTIONS ON THIS CONCEPT?
OKAY, WE CAN KEEP GOING, WE HAVE
1 MORE CONCEPT TO PRESENT.
KRISTI C ONNOLY FROM THE
[INDISCERNIBLE] BRANCH WILL TALK
ABOUT NEW TREATMENTS FOR GENITAL
HERPES.
NTHANKS EMILY AND THANK YOU FOR
THE OPPORTUNITY TO PRESENT OUR
CONCEPT TODAY ON NEW TREATMENTS
FOR GENITAL HERPES, THIS HAS
BEEN A COLLABORATION BETWEEN THE
SECTION ON TRANSMISSION
INFECTIONS BRANCH AS WELL AS
VIROLOGY BRANCH, APPLICATIONS
FOR THIS INITIATIVE WOULD COME
TO BOTH BRANCHES.
SO THIS IS A NEW CONCEPT, FOR
THE TREATMENT--FOR NEW
TREATMENTS FOR GENITAL HERPES
WITH THE OBJECTIVE TO STIMULATE
DEVELOPMENT OF NEW TREEPTS THAT
SUPPRESS SHEDDING AND LESION
FORMATION AND REDUCE
TRANSMISSION AND THIS IS ALL A
BI PHASIC MECHANISM, USING THE
R21 AND R33 FUNDING WHERE AGAIN
APPROXIMATELY 50% OF THE AWARDS
THAT MEET THE MILESTONES AND THE
R21 WOULD BE ANTICIPATED TO MOVE
ON TO THE R33 PHASE OF FUNDING.
WE ARE ANTICIPATING 7-10 R21
AWARDS WITH A FIRST YEAR TOTAL
COST FOR THE INITIATIVE OF
AROUND $3.5 MILLION.
SO FOR PEOPLE LIVING WITH
GENITAL HERPES, THE CURRENT
TREATMENT IS NOT SATISFACTORY,
THIS 1 CYSTS OF LIFE LONG
THERAPY AND THERE'S A GREAT WANT
TO PREVENT SYMPTOMATIC
RECURRENCES, THE DURANNENT
THERAPIES ARE ONLY PARTIALLY
REDUCE SLEDDING AND TRANSMISSION
OF THE VIRUS.
CURRENTENER ACTIVITIES AND
PROJECTSYS FOR HSV RELY ON
NUCLEOICIDE ANALOGUES WHICH HAS
BEEN A PROBLEM FOR IMMUNO
COMPROMISED PATIENTS AFTER LONG
TIME TREATMENT.
AND THIS WAS A RESEARCH GAP THAT
WAS IESHES DENTIFIED FROM THE
WORKSHOP WE HELD IN CONJUNCTION
WITH THE CDC IN THE FALL OF
2022.
THERE ARE LIMITED THERAPEUTIC
OPTIONS CURRENTLY FOR TREATING
HSV INFECTION, BUT WELL IS A
VERY ROBUST BASIC RESEARCH
COMMUNITY, SO THERE'S BEEN A LOT
OF SIGNIFICANT UNDERSTANDING ON
A MOLECULAR BASIS OF
REACTIVATION AND SHEDDING THAT
BEING BE LEVERAGED INTO
TRANSLATIONAL RESEARCH AND
MOVING IT TOWARDS THE
THERAPEUTIC VACCINE OR ANTIVIRAL
DRUG DESEEN SPACE.
THERE HAVE NOT BEEN NOVEL
TARGETS IDENTIFIED SUCH AS
BUDDING PROTEINS OR PACKAGING
PROTEINS THAT COULD BE USED FOR
ANTIVIRAL THERAPY, SHOWN HERE IS
THE GINNY PIG MODEL WHICH IS THE
GOLD STANDARD ANIMAL MODEL THAT
HAS BEEN USED TO RECAPITULATE
CHRONIC AND RECURRENT INFECTIONS
AND A MODEL SUCH AS THIS COULD
BE USED FOR THE DOWN THE ROAD IN
THE R33 PART OF THE FUNDING TO
LOOK AT EFFICACY STUDIES.
SO THIS INITIATIVE FIDS WITHIN
DMID SCIENTIFIC PRIORITIES OF
MAINTAINING A ROBUST PORTFOLIO
BASIC TRANSLATIONAL CLINICAL
RESEARCH AND MICROBIOLOGY AND
INFECTIOUS DISEASES, WOULD
REALLY LIKE TO CAPITALIZE ON ALL
THE BASIC RESEARCH THAT'S BEEN
GOING ON TO TRY TO MOVE MORE
INTO THE TRANSLATIONAL SPACE.
THIS ALSO ALIGNS WITH THE GOALS
OF THE 2023, 2023 TRANSNIH PLAN
FOR HERPES SIMPLEX VIRUS
RESEARCH, SUPPORTING 1 OF THE 4
ARMS THE HSV TREATMENT AND
CURATIVE STRATEGIES THAT WAS
IDENTIFIED.
SO WE WANT TO KEEP THIS
INITIATIVE BROAD.
WE'RE REALLY INTERESTED IN
IDENTIFYING NEW TARGETING
SYSTEMYS, NEW CANDIDATES OF THE
TREATMENT DONE BY HERPES TO
INCLUDE ANTIVIRAL THERAPEUTICS
SUCH AS NONNUCLEOICIDE ANALOGUES
AND IMPROVED NUCLEOTIDES, THESE
COULD ALSO SINNER UTILIZE WITH
CURRENT REGIMENS.
THERAPEUTIC VACCINES ARE ANOTHER
MECHANISM THAT COULD REDUCE OR
ELIMINATE REACTIVATION SIMPLE
TOMS AND TRANSMISSION UNLIKE
PROPHYLACTIC VACCINES WHICH ARE
ADMINISTERED TO PREVENT
ACQUISITION OF AN INFECTION, AND
THERAPY AND PEWIC VACCINE BEING
HELP A PATIENT THAT'S ALREADY
INFECTED, MANAGE THEIR SYMPTOMS.
MONOCLONAL ANTIBODIES VISIT BEEN
POPULAR BEING DEVELOPED THROUGH
A LOT OF OTHER INFECTIONS AND
OTHER THINGS LAST BE SEVERAL
MONTHS AND CLOSE TO A YEAR HAVE
BEEN IN THE PIPELINE FOR OTHER
INFECTIONS, THESE COULD EITHER
TARGET NEUTRALIZE HSE OR ANOTHER
NOVEL STRATEGY TO SUPPRESS
ACTIVATION, ANOTHER TECHNOLOGY
SUCH AS ADDING GENE EDITING OR
CRSPR CAS, OR MEGAN NUCLEACES
CAN BE TARGETED TO SUPPRESS
REACTIVATION AND WE'RE
ENTHUSIASTIC TO SEE WHAT OTHER
KIND OF OTHER NOX FAMILY
ACTIVATORLE TARGETING STRATEGIES
INVESTIGATORS WILL COME UP WITH.
SO THIS LIST IS NOT EXHAUSTIVE.
I WOULD LIKE TO THANK OUR
COUNCIL MEMBERS DR. STEPHANIE
TAYLOR DR. MARY ESTES WHO ARE
SUPPORTIVE OF THERE INITIATIVE
AND THEIR THOUGHTFUL COMMENTS.
THEY WERE SUPPORT OF OF HOW MANY
DIFFERENT MECHANISMS AND THIS
WAS BROAD LOOKINGA THE A LOT OF
DIFFERENT APPROACHES FOR
THERAPEUTICS.
THERE ARE A COUPLE QUESTIONS
THAT CAME UP DURING OUR CALLS,
THE FIRST WAS WHAT IS REALISTIC
FREQUENCY FOR MONOCLONAL
ANTIBODY THERAPY BASED ON WHAT
IS IN DEVELOPMENT FOR OTHER
INFECTIONS AND A FEW EXAMPLES,
COVID-19 HAS MONOCLONALS THAT
ARE CURRENTLY LASTING 6 MONTHS,
THERE ARE NUMEROUS CANDIDATES IN
THE HIV FIELD, LASTING 3-6
MONTHS AND ZIKA VIRUS HAS A
CANDIDATE THAT WILL PROJECT TO
LAST UP TO 9 MONTHS, SO WE THINK
THAT SOMETHING AALONG THOSE
LINES CAN BE ATTAINABLE FOR HSV
AS WELL.
AND THE OTHER QUESTION WOULD BE
WHAT WOULD BE THE ANTICIPATED
MAXIMUM BUDGET FOR THE BI PHASIC
AWARD.
SO FOR THE R21 PORTION, THE
DIRECT COST WOULD BE 275,000
OVER 2 YEARS, AND FOR THE R33,
THE PROJECTS THAT MEET THEIR
MILESTONES AND MAKE THAT
TRANSITION WOULD THEN BE AWARDED
300,000 ANNUALLY FOR 3 YEARS.
AND WITH THAT I WILL BE HAPPY TO
TAKE ANY QUESTIONS.
RIGHT ON TIME.
>> THANK YOU KRISTI.
ANY QUESTIONS OR COMMENTS IN
OKAY, THANK YOU.
SO WE DO NEED EVERYBODY'S VOTES
AND ADDITIONAL COMMENTS, WELL,
IT'S NEW, WHERE DO YOU VOTE, I
THINK IT'S--IT'S IN THE
ELECTRONIC COUNCIL BOOK BUT IF
YOU NEED HELP THIS WOULD BE THE
TIME TO ASK FOR IT.
CAN EVERYBODY FIND THE PLACE TO
RECORD YOUR--LINDA BLACKENSDADT,
IS IT CRYSTAL CLEAR IN OKAY,
GOOD.
OUR HELPERS HAVE ARRIVED BUT
EXCEPT FOR RECORKING THE VOTES,
I THINK OUR MEETING CAN
CONCLUDE, PEOPLE CAN ...