>> ALL RIGHT. LADIES AND
GENTLEMEN, I WOULD LIKE TO
WELCOME YOU TO THE BREAKOUT
SESSION ON EXPANDING DRUG
INDICATIONS.
MY NAME IS [INDISCERNIBLE]. I'M
ONE OF THE INTRAMURAL
INVESTIGA
INVESTIGATORS IN NIAD AND ALSO A
CO-ORGANIZER AND MEMBER OF
STEERING COMMITTEE FOR THIS
MEETING SO SOME -- I WILL A
LITTLE INTRODUCE THE SESSION AND
WILL HAVE SIX WONDERFUL SPAESHGS
TO TALK ABOUT THEIR EXPERIENCE
IN THIS ARENA.
AFTER THAT WE WILL HAVE Q & A
SESSION.
I HOPE THAT MANY OF YOU ALREADY
PARTICIPATED IN THE PREVIOUS
SPLIT-OUT SESSIONS.
YOU KNOW THAT YOU CAN POST
QUESTIONS USING THE QUESTION
PANEL ON THE RIGHT SIDE.
DRUGS ACHIEVED ALREADY GREATER
SUCCESS FOR SECOND INDICATION
COMPARED TO ORIGINAL INDICATION
AND PERHAPS THE MOST LUSTROUS
EXAMPLE OF THIS IS GOP1 AGONISTS
ANTIDIABETIC DRUGS BEING
CURRENTLY REPURPOSED FOR
TREATMENT OF OBESITY AND
NEVERTHELESS AS PATH TOWARDS
TREATING NEW DISEASES
REPURPOSING SEEMS TO BE MUCH
MORE ADVANTAGEOUS TO ACADEMIC
INVESTIGATORS AND IN PUBLIC
COMPARED TO PEOPLE IN
PHARMACEUTICAL INDUSTRY AND
[INDISCERNIBLE] FROM N CAPS WILL
EXPLAIN MANY REASONS THIS MIGHT
BE THE CASE.
WE WILL THEN HERE A FEW SUCCESS
STORIES FACILITATED BY THE
ORPHAN DRUG ACT EFFECTIVE
LEGISLATIVE SOLUTION TO PART OF
THIS PROBLEM.
FOR THOSE THAT ARE WORKING ON
CHRONIC UNTREATABLE DISEASES
EFFECTING LARGER PROPORTION OF
POPULATION THAN ONE COVERED BY
OR FAN DRUG ACT, I WANT TO
HIGHLIGHT THAT LACK OF ACCESS TO
THERAPEUTIC AGENTS LIMIT ABILITY
TO FULFILL NIH MISSION.
SAYING LACK OF ACCESS I SAY
THREE MAJOR CATEGORIES OF DRUGS
ONE IS DRUGS ARE FDA APPROVED
THAT ARE PROHIBITIVELY EXPENSIVE
AND NONE CAN REALLY GO AND BUY
THEM FOR PROOF OF PRINCIPLE
CLINICAL TRIAL.
REASONABLE SAFETY PROFILE THAT
DIDN'T HAVE SUFFICIENT EFFICACY
FOR PRIMARY INDICATION.
THEORETICALLY DRUGS MIGHT BE
RESEQUENCED IN PRACTICAL SENSE
THEY ARE UNUSABLE.
WE CAN'T CROSS-REFERENCE INDS
THAT ARE SUPPORTED INFORMATION
THAT IS NOT IN PUBLIC DOMAIN.
LAST CATEGORY OF DRUGS ARE IN
DEVELOPMENT FOR PRIMARY
INDICATION.
SOMETIMES DRUG COMPANY MAY NOT
BE WILLING TO ENGAGE IN
DEVELOPING SAME DRUG FOR
SECONDARY INDICATION THAT IS
SOMETIMES BASED ON
UNSUBSTANTIATED FEAR THAT
SOMEHOW SECONDARY INDICATION MAY
CHALLENGE OR PREVENT PRIMARY
INDICATION TO BE SUCCESSFUL.
THIS FEAR IS NOT SUBSTANTIATED.
SO, I MENTIONED NIH MISSION DR.
BARR CONTINUE OELI NEW NIH
DIRECTOR MENTIONED AS WELL
MISSION TO SEEK FUNDAMENTAL
KNOWLEDGE ABOUT NATURE AND
BEHAVIOR OF LIVING SYSTEMS TO
APPLY KNOWLEDGE TO ENHANCE
HEALTH AND LENGTHEN LIFE AND
REDUCE ILLNESS AND DISABILITY.
WE CAN DO IT EFFECTIVELY IN
ANIMAL MODELS AND IN VITRO
STUDIES AND DO IT BY
ESTABLISHING CORRELATION BETWEEN
BIOMARKERS REFLECTING DISEASE
PROCESS AND CLINICAL OUTCOMES
FOR EXAMPLE OF DISEASE
PROGRESSION.
HOWEVER, IN ORDER TO DO FINAL
STEP IN KNOWLEDGE ACQUISITION
THAT IS IN STEP OF VALIDATION WE
NEED ACCESS TO DRUGS BECAUSE
ONLY WAY THAT YOU CAN VALIDATE
KNOWLEDGE IS IN INTERVENTIONAL
CLINICAL TRIAL TAKING DRUG
INHIBITING PROPOSED DISEASE
MECHANISM AND SHOWING THAT IF IT
INHIBITS DISEASE MECHANISM IT
ALSO INHIBITS DISEASE
PROGRESSION AND LAST STEP IS
MOST IMPORTANT IN YURN ANY TO
TRANSLATING DRUGS TO HUMAN
HEA
HEALTH.
INTRAMURAL RESEARCH PROGRAM IS
UNIQUELY AMENABLE TO THIS LAST
STEP IN KNOWLEDGE VALIDATION AND
THANKS TO NIH CLINICAL CENTER
THESE ARE DEEPLY PHENOTYPING
DISEASES DEVELOPING BIOMARKERS
WITH CLINICAL VALUE AND
PREDICTIVE MODELS USING TOOLS IN
PROOF OF PRINCIPLE CLINICAL
TRIALS MAKING THEM ECONOMICAL
AND ASSURING THAT THE KNOWLEDGE
IS GAINED WHETHER TRIAL IS
POSITIVE OR NEGATIVE.
INDEED, WE LIVE IN A TIME WHEN
INCREASING PREVALENCE OF CHRONIC
DISEASES THREATENS VIABILITIES
AND AREA I WORK THAT IS
MARGINALLY THUS FAR AND LIKELY
THAT EFFECTIVE TREATMENTS OF
DISEASES WILL REQUIRE
DEVELOPMENT OF THERAPEUTIC
COMBINATIONS SIMULTANEOUSLY
TARGETING MULTIPLE DISEASE
MECHANISMS THAT REPRESENTS
CHALLENGE BEYOND EVERYTHING THAT
I MENTIONED THUS FAR THAT WE ARE
HAPPY TO HAVE DOCTORS TO ADDRESS
THIS PROBLEM AND UNDOUBTEDLY
EXPANDING ACCESS TO EXISTING
DRUGS FOR PROOF OF PRINCIPLE
CLINICAL TRIALS HAS POTENTIAL TO
BENEFIT STAKEHOLDERS AND HOPE
THIS SESSION WILL TRANSFORM
VISION TO SEE WIN/WIN SOLUTIONS
GOING FORWARD.
WITH THAT I WILL THANK YOU FOR
BEING HERE.
I WILL GIVE THE SPEAKER TO DR.
COLIS.
>> THANK YOU. THAT WAS A GREAT
INTRODUCTION TO THE SESSION.
I'M CHRISTINE AND I'M EXTRAMURAL
PROGRAM DIRECTOR THAT I HEAD UP
AN OFFICE CALLED OFFICE OF --
HERE AT THE NIH.
I WILL TELL YOU ABOUT TWO
DIFFERENT SORT OF SCENARIOS THAT
FIT INTO THIS SPACE.
THE FIRST IS A DRUG
REPOSITIONING SCENARIO.
THIS IS A CASE WHERE WHEN I
FIRST JOINED AND WAS BROUGHT ON
BOARD IN 2012 TO LEAD FOR
PROGRAM REPOSITIONING WHERE DR.
COLLINS HAD ACTUALLY ESTABLISHED
PARTNERSHIPS WITH LARGE
PHARMACEUTICAL COMPANIES PFIZER
AND [INDISCERNIBLE] JANSSEN AND
NEGOTIATED THAT THEY WOULD
ACTUALLY MAKE AVAILABLE SOME
CLINIC-READY ASSETS THAT HAD NOT
MADE IT TO MARKET YET GENERALLY
DEPRIORITIZED BY THEM AND
REFERRED TO OFTEN AS SHELFED
COMPOUNDS IF THEY WOULD MAKE
THEM KNOWN TO RESEARCH COMMUNITY
NIH THROUGH MCATS COULD PROVIDE
CLINICAL TRIALS EXPLORING
INDICATIONS FOR WELL-DEVELOPED
ASSETS AND A THREE-WAY
PARTNERSHIP WAS ESTABLISHED AND
IN IT PHARMACEUTICAL COMPANIES
AGREED TO MAKE AVAILABLE
KNOWLEDGE OF THESE ASSETS THAT
WOULD BE SORT OF MINIMAL
KNOWLEDGE THAT WOULD BE OR WE
WOULD PUT IN PUBLIC DOMAIN.
WE POSTED IT ON THE MCATS
WEBSITE.
AND THROUGH THIS PROCESS THAT I
WILL EXPLAIN MORE ABOUT THE
PROCESS THROUGH THAT PROCESS FOR
PROJECTS THAT WOULD END UP
MOVING FORWARD EVENTUALLY AND
TRIALS MOVING FORWARD, COMPANIES
MADE CLINICAL SUPPLIES AVAILABLE
AT NO COST TO NIH AND NO COST TO
INVESTIGATORS AND THAT CLINICAL
SUPPLY INCLUDED MATCH PLACEBO
AND THEY MADE A PI ACTIVE
PHARMACEUTICAL INGREEDIENT
AVAILABLE IF PRECLINICAL STUDIES
WERE NEEDED.
THAT IS THEIR CONTRIBUTION
THROUGH THIS PARTNERSHIP AND
TURNING TO ACADEMIC
INVESTIGATORS AND NIH INTRAMURAL
PROGRAM TO SEE IF RESEARCHERS
HAD IDEAS FOR INDICATIONS THAT
THESE WELL-DEVELOPED ASSETS
MIGHT BE GOOD FOR.
THE -- YOU KNOW VALUE FOR THEM
YOU KNOW IF YOU IMAGINE THAT YOU
ARE A RESEARCHER SITTING IN AN
ACADEMIC INSTITUTION OR SITTING
AT IRP AND HAVE WHAT YOU BELIEVE
TO BE A STRONG HYPOTHESIS FOR
PARTICULAR ACTION AND MODULATION
FOR TARGET WITH SMALL MOLECULE
COULD HAVE POSITIVE IMPACT ON
DISEASE AND YOU WANT TO PURSUE
THAT AND KNOW IT WILL TAKE YOU
OVER A DECADE AND GET TO POINT
YOU ARE TAKING SOMETHING INTO
THE CLINIC.
THROUGH THIS PROGRAM WE WERE
GETTING CLINIC READY ASSETS FROM
PHARMACOMPANY IF YOUR TARGET
MATCHED WITH MECHANISM OF ACTION
OF DRUG BEING OFFERED BY
PHARMACEUTICAL COMPANY YOU COULD
TEST IN HUMANS IN LESS THAN A
YEAR.
THE -- SO IT IS THAT NEW IDEA OF
NEW USE FOR THESE WELL DEVELOPED
ASSETS THAT WE WERE TURNING TO
ACADEMIC PARTNERS FOR AND
NIHNCATS WOULD PROVIDE SUPPORT
FOR CLINICAL TRIALS.
ANOTHER IMPORTANT THING WE
OFFERED WAS WE HAD BEFORE THIS
INITIATIVE WAS LAUNCHED NIH HAD
NEGOTIATED WITH EACH OF THE
PHARMACEUTICAL COMPANIES
COLLABORATIVE RESEARCH
AGREEMENTS THAT WE CALLED
TEMPLATE COLLABORATION RESOU
SEARCH AGREEMENTS.
EACH OF THE PHARMACEUTICAL
COMPANIES SERVING AS A STARTING
POINT FOR NEGOTIATION WITH
ACADEMIC INSTITUTION AND IRP
THAT WOULD COMMENT WITH AN IDEA
FOR COLLABORATION.
WITHOUT GOING INTO TOO MUCH
DETAIL OF THE PROCESS, IT KICKS
OFF WITH A PRE-APPLICATION FROM
THE INVESTIGATORS.
NIH WE ADVERTIZED FUNDING
OPPORTUNITY ALONG WITH A LIST OF
ASSETS COMING FROM THE COMPANIES
THAT WERE ORDERED ACCORDING TO
MECHANISM OF ACTION AND SEND US
A PRE-APPLICATION AND IDEA IT IS
A VERY SHORT PRE-APPLICATION AND
NO THE ASKING FOR MONEY AT THIS
POINT YOU DON'T HAVE ENOUGH
INFORMATION AND JUST ENOUGH FOR
YOU TO TELL I WANT TO ACTUALLY
TALK WITH THIS COMPANY ABOUT TO
LEARN MORE ABOUT THIS PARTICULAR
ASSET THEY HAVE.
IT MIGHT BE USEFUL FOR THE
DISEASE I'M STUDYING THAT WENT
THROUGH EXTERNAL REVIEW.
PRE-APPLICATIONS WENT THROUGH
EXTERNAL REVIEW.
IF YOU MADE IT THROUGH THAT GATE
YOU HAVE CONTACT WITH ASSET
PROVIDER AND FIRST THING TO DO
IS SIGN NON-DISCLOSURE AGREEMENT
AND ACADEMIC RESEARCHER AND IRP
RESEARCHER IS SHARING
INFORMATION WITH THE COMPANY
THAT IS TRYING TO CONVINCE THEM
THAT THIS WOULD BE A WORTHWHILE
THING FOR NIH TO INVEST IN AND
PURSUE AND COMPANY IN MEANTIME
IS NOW DISCLOSING MUCH MORE DATA
THAN WE WOULD HAVE PUT ON OUR
WEBSITE.
SO, BOTH PARTIES AT THAT POINT
WOULD HAVE TO AGREE IT IS WORTH
MOVING FORWARD WITH AND FULL
APPLICATION REQUESTING FUNDING
SHOULD BE SUBMITTED TO NCATS.
COMPANIES MIGHT SAY WE DON'T
FEEL CONVINCED OR HAVE DONE
OTHER STUDIES CLOSELY RELATED TO
THIS DISEASE AND DON'T THINK IT
WILL WORK AND DON'T WANT TO
PURSUE IT.
IN THAT CASE NO APPLICATION
WOULD COME TO US.
ACADEMIC RESEARCHER MIGHT HAVE
LOOKED AT IT AND SAID YEAH.
THIS PARTICULAR SIDE EFFECT THAT
YOU WERE SEEING WHILE IT IS
STILL, YOU KNOW, REASONABLE
SAFETY PROFILE FOR THIS
PARTICULAR LOCATION POPULATION
THAT WON'T WORK AND IT DOESN'T
GET PURSUED OR MOVE FORWARD.
ALL THESE ASSETS HAVE AND FAILED
TO HAVE SAFETY PROFILES
GENERALLY DISCONTINUED FOR
BUSINESS REASONS AND REALLY
THERE WAS NO REASON
SCIENTIFICALLY THAT WE COULDN'T
ACTUALLY CONTINUE TO PURSUE
THEM.
WE NEEDED STRONG HYPOTHESIS AND
EVIDENCE THAT THERE WAS A GOOD
TIE BETWEEN THE MECHANISM OF
ACTION AND OF DRUG AND DISEASE
THAT THE INVESTIGATOR WAS
INTERESTED IN.
FOR THE -- FOR THE APPLICATIONS
THAT CAME TO THE NIH THEY WENT
THROUGH PEER REVIEW WE AS I SAID
PROVIDED SUPPORT FOR PHASE 1 IF
NEEDED AND PHASE 2 CLINICAL
TRIALS AS WELL AS NON-CLINICAL
STUDIES THAT MIGHT BE NEEDED.
FOR EXAMPLE WE HAD A CASE WHERE
WE HAD AN ASSET THAT HAD BEEN
DEVELOPED BY ASTO ZEN EBBINGA
THAT WAS EXCLUSIVELY EXPLORED
FOR VARIOUS ONCOLOGY INDICATIONS
AND THEY HAD ONLY DONE TOP
STUDIES FOR SHORT-TERM USE OR
SHORT-TERM ADMINISTRATION AND
NEW IDEA WAS TO USE THIS FOR
ALZHEIMER'S THAT WOULD BE
CHRONIC ADMINISTRATION.
WE HAD TO SUPPORT NON-CLINICAL
STUDIES TO MAKE SURE THAT THIS
WOULD BE OKAY TO ADMINISTER THIS
DRUG AT A LOWER DOSE AND MUCH
LONGER PERIOD OF TIME.
THAT WOULD BE EXAMPLE OF
NON-CLINICAL STUDIES THAT WOULD
HAVE TO BE DONE WITH AN ALREADY
WELL-DEVELOPED ASSET THAT HAS
BEEN THROUGH ALREADY CLINICAL
TRIALS.
AND SO THROUGH THE MODEL WHAT
MCATS WAS TRYING TO TEST WAS THE
MODEL OF PARTNERSHIP.
IF A COMPANY MAKES LIMITED
INFORMATION ABOUT ASSETS
AVAILABLE WILL IT BE SUFFICIENT
TO JUMP START POTENTIAL
PARTNERSHIP AND COLLABORATION?
YOU KNOW, OUR HOPE WAS THAT WE
WOULD DEMONSTRATE THIS MODEL
COULD WORK AND USING TEMPLATE
COLLABORATION AGREEMENTS AS A
STARTING POINT WOULD RELIEVE
NEGOTIATION AND BURDEN OFF THE
LEGAL TEAMS AND COMPANIES AND
THAT THIS WOULD ACTUALLY BE A
WORTHWHILE THING FOR COMPANIES
TO PURSUE ON THEIR OWN WITHOUT
HAVING NCATS OR NIH AND IN FACT
ASTROZEN EBBING KA IF YOU GOOGLE
NOW AND WANT YOU TO PAY
ATTENTION TO THE SESSION AND
WHEN IT IS OVER AND GOOGLE
ASTROZEN EBBINGA YOU WILL SEE
THEY HAVE DONE WHAT WE DID WITH
OUR PROGRAM.
THEY HAVE A SET OF COMPOUNDS
AVAILABLE FOR EXPLORATION IN
PRECLINICAL STUDIES AND HAVE
SOME AVAILABLE FOR EXPLORATION
ON CLINICAL STUDIES AFTER YOUR
IDEA AND PROPOSAL MAKES IT
THROUGH A REVIEW PROCESS
CONDUCTED BY ASTO ZEN EBBINGA
THAT THEY DECIDE WOULD BE WORTH
PURSUING AND EVEN THOUGH ASSETS
ARE DEVELOPED BY THEM IT STILL
TAKES TIME AND RESOURCES ON
THEIR PART TO PURSUE A
PARTNERSHIP OR COLLABORATION
WITH ANYBODY.
THIS WAS A MODEL THAT WAS
SPECIFICALLY DEVELOPED FOR DRUG
REPOSITIONING.
REPOSITIONING SOMETHING THAT
HASN'T MADE IT TO MARKET YET
ACTUALLY.
MOST COMMON QUERY MY OFFICE
DWETS IS ACTUALLY FROM PEOPLE
WHO ACTUALLY WANT TO PURSUE
REPURPOSING A MARKETED DRUG.
THIS IS NATURAL.
THESE ARE THE THINGS THAT PEOPLE
KNOW THE MOST ABOUT.
SO, OF COURSE, THIS IS WHAT
PEOPLE WANT TO PURSUE.
UNFORTUNATELY, THIS IS EXTREMELY
CHALLENGING.
THERE IS LIMITED PATHS TO A
RETURN ON INVESTMENT.
WHEN YOU HAVE TO, YOU KNOW,
STILL PAY FOR CLINICAL TRIALS
AND EVERYTHING.
REASON THERE IS A LIMITED
ABILITY TO RECOUP INVESTMENT YOU
MAKE IS BECAUSE IN MOST CASES
DRUGS ALREADY HAVE GENERIC
COMPETITORS ON THE MARKET.
IF THEY DON'T HAVE THEM NOW THEY
WILL SHORTLY HAVE GENETIC
COMPETITORS ON THE MARKET YOU
MIGHT BE ABLE TO BE AWARDED A
USE PATENT FOR THIS MARKETED
DRUG BECAUSE THERE ARE GENERIC
COMPETITORS ON THE MARKET, THERE
IS NOTHING TO PREVENT THE PAYERS
REIMBURSING FOR GENERIC OR
PHYSICIAN TO PRESCRIBE GENERIC
OR PATIENT TO REREQUEST THE
GENERIC DRUG BECAUSE THEY HAVE
THE EXPANDED LABEL FOR IT.
IT MAKES IT EXTREMELY DIFFICULT.
THERE ARE PATHS THAT WILL WORK.
THEY HAVE BEEN MENTIONED THAT
CHANGING FORMULATION IS A
STRATEGY THAT WILL WORK AND WE
WILL HEAR MORE ABOUT THAT IN THE
SESSION.
ANYTHING WHERE YOU CHANGE ROUTE
OF ADMINISTRATION OR CHANGE
ACTIVE INGREDIENTS TO HAVE TWO
ACTIVE INGREDIENTS AND
COMBINATION THERAPY OR IF YOU
CHANGE SO YOU HAVE AN EXTENDED
RELEASE FORMULATION, THESE ARE
THINGS WHERE YOU WOULD HAVE THAT
HAVING THAT PATENT THAT WOULD
ACTUALLY BE USEFUL OR HAVING
EXCLUSIVITY FROM THE FDA WOULD
BE USEFUL AND AS LONG AS THERE
IS A GENETIC COMPETITOR IT IS
EXTREMELY NO WAY FOR YOU TO
RECOUP THAT INVESTMENT.
WHEN I SAY THAT, THAT IS FROM
THE PERSPECTIVE FROM A DRUG
DEVELOPER, FROM A DRUG
DEVELOPER'S PERSPECTIVE THERE IS
LITTLE MOTATION FOR THIS REASON
HAVING GENERICS ON THE MARKET
THINKING FROM PERSPECTIVE FROM A
PAYER AND INSURANCE COMPANIES
THEY ARE ONES THAT WOULD STAND
TO BENEFIT.
IF YOU IMAGINE THAT SOMEBODY HAS
AN IDEA FOR REPURPOSING A
MARKETED DRUG TO TREAT A
CONDITION THAT IS COSTLY TO THE
HEALTHCARE SYSTEM BECAUSE OF A
LARGE NUMBER OF PATIENTS OR
BECAUSE AND NO TREATMENT IS
AVAILABLE OR CURRENT TREATMENTS
ARE EXPENSIVE AND THERE IS SEC
WELLY AND NOT TREATMENT
AVAILABLE THAT MAKE IT COSTLY TO
THE HEALTHCARE SYSTEM AND FROM
PAYER'S PERSPECTIVE DISEASES ARE
COSTING LOTS OF MONEY AND IF WE
CAN TREAT IT WAY GENERIC DRUG
THAT COULD BE INEXPENSIVE COULD
MAKE A SIGNIFICANT DIFFERENCE
FOR THEM.
SO FAR WE ARE NOT THOUGHT ABOUT
THE PAYERS OR FOCUSED ON PAYERS
AND SPACE OF REPURPOSING GENERIC
DRUGS THIS IS SPACE WE WILL NEED
TO GET INTO AND IS THE COMMUNITY
WE HAVE TO ENGAGE AND AS YOU
KNOW THAT IS NOT SOMETHING THEY
ARE THINKING ABOUT THAT WILL
TAKE VERY INTENTIONAL
INTERACTIONS WITH THEM TO
EXPLAIN TO THEM WHY THIS WILL BE
BENEFICIAL TO THEM AND WHY THIS
IS SOMETHING THEY SHOULD START
TO THINK ABOUT.
I'LL STOP THERE AND HAND IT TO
DEDETO INTRODUCE THE NEXT
PANELIST, I SHOULD SAY.
>> THANK YOU. THIS WAS A VERY
NICE INTRODUCTION AND KNOW ABOUT
THE ASTROZEN EBBINGA PROGRAM
THAT IS PRETTY AWESOME. NEXT
SPEAKER IS ANJUNG.
TELL US ABOUT YOURSELF AND YOUR
WORK.
>> THANK YOU DEDEAND CHRISTINE
FOR THAT OVERVIEW.
I HAVE BEEN WORKING IN THE
PHARMACEUTICAL BIOTECH CRO
INDUSTRY AND CAREER PARTNER AT A
VENTURE FUND AND RECENT PRODUCT
IS STARTING MY OWN COMPANY
CALLED RIA THERAPEUTIC THAT IS
NAMED AFTER MY FATHER WHO PASSED
AWAY FROM ALS HE WAS DIAGNOSED
IN DECEMBER OF 2010 AND AFTER
DIAGNOSIS I BECAME INVOLVED IN
ALS COMMUNITY IF YOU WILL WENT
TO CONFERENCES TALKING WITH ALS
RESEARCHERS AND CLINICIANS AND
YOU KNOW EVEN JOINED THE BOARD
OF THE MUSCULAR DISTROPHY
ASSOCIATION AND LARGEST
NON-PROFIT FOR NEUROMUSCULAR
DISEASES IN THE US AND IN NUMBER
OF YEARS I CAME ACROSS SEVERAL
CLINICAL STAGE DRUGS THAT WERE
ALL DRUGS THAT AT LEAST WENT
THROUGH PHASE 2.
THEY ALL WERE ORIGINALLY
DEVELOPED FOR NEUROLOGICAL
INDICATIONS THAT WERE, YOU KNOW,
NOT ALS.
AND, YOU KNOW, DEPRIORITIZED IF
YOU WILL FOR MOSTLY BUSINESS
REASONS THAT CERTAINLY SOME NONE
OF THEM WERE DUE TO SAFETY
REASONS THAT IS IMPORTANT.
WHEN I CAME ACROSS THEM I'M NOT
A SCIENTIST.
I KNEW ENOUGH THAT THEY LOOKED
LIKE THEY COULD HAVE POTENTIAL
IN ALS.
I WENT TO REAL ALS EXPERTS AND
ASKED THEM TO CONDUCT DILIGENCE
ON VARIOUS DRUGS AND MECHANISMS
AND TARGETS AND POTENTIAL TO
TREAT ALS AND SMALL MOLECULE AND
BLOOD BRAIN BARRIER AND OFFER
PROTECTION AROUND THE MOTOR
NEURON.
AND THE EXPERTS CAME BACK TO ME
AND SAID ABSOLUTELY THERE WERE
REASONS AND BIOLOGIC RATIONALE
WHY THESE DRUGS COULD WORK AND I
WENT BACK TO EACH OF THE
COMPANIES AND SAID YOU DON'T
APPEAR TO BE YOU KNOW PUTTING
LOTS OF PRIORITY ON XOUCOMPOUND
AND DEVELOPMENT AND THERE IS
OPPORTUNITY HERE AND I WILL TELL
YOU ABOUT IT AND ALS IS A HIGHLY
UNMET NEED AND DEADLY DISEASE
AND NOT WELL-UNDERSTOOD AND VAST
MAJORITY OF LS PATIENTS HAVE
SPORADIC ALS THAT IS NOT
NECESSARILY HAVING DEFINED
ETIOLOGY OR GENETIC MAKEUP.
IT TOOK A WHILE AND ALMOST FOUR
YEARS.
BUT, RIA HAS LICENSED FIVE
CLINICAL STAGE COMPOUNDS AND
COMPLETED AT LEAST PHASE 2.
YOU KNOW, I KIND OF JOKE THAT WE
ARE THE ONLY BIOTECH IN THE
WORLD THAT HAS MORE DRUGS THAN
PEOPLE, BELIEVE IT OR NOT.
WHAT WE HAVE BEEN WORKING ON
RECENTLY IS TRYING TO DEVELOP
DRUGS FURTHER AND THERE IS GAP
FILLING TO DO AND DRUGS ARE
OLDER AND HAVE TO BE
MANUFACTURED AT NEW SITES AND
VALIDATE MANUFACTURING PROCESSES
AND HAVE TO GO THROUGH
REGULATORY PATHWAY TALKING TO
REGULATORY AGENCIES ABOUT A NEW
INDICATION AND WE ARE CURRENTLY
GOING THROUGH THAT HOPING TO
LAUNCH A 5-ARM PLATFORM WITH
DRUGS AND MECHANISMS AND
TREATMENT OF ALS THAT IS AN
AMBITIOUS TREATMENT AND
HIGHLIGHTING ABOUT PROJECTS IS
IF YOU LOOK AT FUTURE OF
NEURODEGENERATIVE DISEASES AND
DR. STOT WILL TALK ABOUT THIS
SPECIFICALLY AROUND PARKINSON'S
AND NUMBER OF NEURODEGENERATIVE
DISEASES WILL REQUIRE
COMBINATION TREATMENT IN THE
FUTURE ALL THESE REQUIRE
COCKTAILS OF DRUGS WITH
DIFFERENT MECHANISMS AND ALS IS
NOT GOING TO BE DIFFERENT THAN
THAT. MULTIFACTORIAL DISEASE
AND IN ADDITION TO DEVELOPING
DRUGS INDIVIDUALLY AS A
MONOTHERAPY WE HAVE STARTED TO
DO COMBINATION DEVELOPMENT IN
PRECLINICAL ALS MODEL TESTING
DRUGS BY THEMSELVES AND IN
COMBINATION WITH EACH OATH AND
INVEEF TROE MODELS AND IN VIVO
MODELS THAT IS LIKE A BAIK OFF
AND TRYING TO FIND BEST
COMBINATION AND EVENTUALLY MOVE
FORWARD AND NOT FOR PAINT AT
HEART FOR SURE AND CERTAINLY IS
MORE CHALLENGING FROM THE
PERSPECTIVE OF THESE FIVE DRUGS
THAT THEY ARE IN SENSE THEY ARE
A NEW CHEMICAL ENTITY AND
LOOKING AT COMBINATION
DEVELOPMENT IN ONCOLOGY IT IS
APPROVED DRUGLIKE NTRUDA ANDS
DOENS OF APPROVED DRUG AND IN
CASE OF ALS YOU DON'T HAVE A
TRULY ESTABLISHED STANDARD OF
CARE NETWORKS AND LOOKING AT
COMBINING CHEMICAL ENTITIES
DEVELOPING THIS WAY THAT IS RARE
IN OUR INDUSTRY TO DO AND
FINDING DRUGS UNDER ONE ROOF AND
TRYING TO GET FIVE BIOTECHES TO
COLLABORATE ON COMBINATION
DEVELOPMENT THAT WILL BE
CHALLENGING TO SAY THE LEAST
AND.
ONE THING THAT IS GIVEN A
BACKGROUND WORKING AT BIG
PHARMA-AND AT A VENTURE FUND AND
MY -- YOU KNOW, MY WORK
EXPERIENCE WAS PRIMARILY AROUND
LICENSING AND MERGERS AND
ACQUISITIONS AND KNEW THAT IT
WOULD BE A LOT MORE CHALLENGING
TO PITCH THIS STORY, IF YOU
WILL, TO POTENTIAL INVESTORS IF
THESE WERE APPROVED DRUGS THAT
WERE BEING REPURPOSED.
AGAIN, AS CHRISTINE AND
DEDETALKED ABOUT, THESE DRUGS
WOULD REPURPOSE WAY I SEE IT AND
BCS AND BIG PHARMA-AND THEY SEE
IT AS THESE ARE OLDER DRUGS THAT
HAVE GENERICS AND SOMEBODY IS
TRYING TO CREATE A NEW VERSION
OR COULD BE REFORMULATED OR
COULD BE A DIFFERENT STRENGTH,
ET CETERA.
EFFECTIVELY THESE ARE DRUGS WITH
GENERIC COMPOUNDS AVAILABLE --
OVERALL, I WOULD HAVE TO SAY
THAT MY PERSONAL EXPERIENCE HAS
BEEN IT IS MORE CHALLENGING TO
PIT YOUR STORY WITH REPURPOSED
DRUGS UNFAIRLY, PERHAPS, TO
INVESTORS AND PHARMACEUTICAL
COMPANIES THAN NEW CHEMICAL
ENTITIES.
I WILL PAUSE AND PASS IT OVER
AND I'M HAPPY TO ANSWER
ADDITIONAL QUESTIONS THAT
CERTAINLY POTENTIAL ROLE OF THE
NIH AND HOW THEY COULD PLAY WHAT
ROLE THEY COULD PLAY WITH A
REPOSITORY FOR QUOTE ON QUOTE
SHELFED PHARMACEUTICAL ASSETS
THAT WE HAVE TO HAVE A CARROT
APPROACH AND OFFER INCREASED
LEVELS OF PROTECTION FOR
PHARMACEUTICAL COMPANIES TO BE
REALLY MORE INTERESTED IN
PARTICIPATING IN PROGRAMS SUCH
AS A ONE THAT CHRISTINE
DESCRIBED EARLIER.
>> GREAT. THANK YOU. THIS WAS
REALLY INTERESTING PERSPECTIVE.
YOU KNOW, I DO WANT TO SAY THAT
SOMETIMES YOU MENTIONED THAT --
THAT YOUR COMPANY MAY HAVE FEWER
PEOPLE THAN DRUGS AND WAS
IMPRESSED BY PLENARY SPEAKERS
WHO MANAGED TO BRING DRUG TO FDA
APPROVAL WITH MINIMAL STAFFING;
RIGHT?
ONE OF THOSE PEOPLE THAT I
TOTALLY ADMIRE IS NEXT SPEAKER
RAPHAELA WITH, YOU KNOW, A SMALL
GROUP WITH DRAGS FOR FDA
APPROVALS FOR PATIENTS AND
RAPHAELA, PLEASE.
>> THANK YOU VERY MUCH DEDETO
THIS PANEL AND MEETING AND
VIOLATING A LITTLE BIT
CONVENTION THAT I HAVE SLIDES
THAT I HOPE THAT THESE WILL
ACTUALLY HELP TO TELL THE STORY
I WANT TO TELL YOU.
LET ME SEE IF I CAN SHARE THIS.
WHAT YOU SEE IS THE CLINICAL
CENTER AND HOPE YOU SEE THIS
WITH TRANSLATIONAL RESEARCH
CURSE AND I'M CHIEF OF THE
TRANSLATIONAL AUTO INFLAMMATORY
TRANSLATION SECTION AND
RHEUMATOLOGIST IN TRANSLATIONAL
RESEARCH AND PASSION IS TO SEE
AND TREAT YOUNG CHILDREN AND
ADULTS WITH RARE INFLAMMATORY
CONDITIONS REFERRED TO US FROM
NATIONAL AND INTERNATIONAL
SOURCES AND PATIENTS ARE OFTEN
TO COMMUNITIES AND NO GOOD
TREATMENTS AND GOAL TO DISCOVER
GENETIC CAUSE AND BY DOING SO
IDENTIFY PATHOGENIC PATHWAYS
BIOMARKERS ALLOWING US TO
DEVELOP ON TREATMENT WITH
PROTOCOLS WITH TARGETED AGENCIES
WHEN EFFECTIVE IMPROVE LIVES OF
CHILDREN AND UNBURDEN AND ALLOW
THEM TO BE TREATED IN
COMMUNITIES AND ALSO BY SEEKING
REGULATORY APPROVAL MAKING IT
POSSIBLE AND WE HAVE A LARGE
COHORT OF OVER 600 PATIENTS IN
WIDE [INDISCERNIBLE] THAT HAVE
NOT GENETICALLY SOLVED AND CLOSE
TO 50% AND BE ABLE TO IDENTIFY
PATHWAYS THAT COULD BE TARGETED
THAT BRINGS US TO NEXT PROBLEM.
WE ARE ABLE TO UNCOVER
PARTICULAR REGIONS USING EX-HOME
AND WHOLE GENOME SEQUENCES IN
2011 AND CAUSES MANY ARE
[INDISCERNIBLE] IN PATIENTS WITH
AUTO INFLAMMATORY PHENOTYPES AND
HOWEVER EACH DISEASE IS RARE AND
NO THE JUST RARE BUT ULTRA RARE.
MOST CONDITIONS SHOWN HERE HAVE
A PREVALENCE OF LESS THAN 320 IN
THE UNITED STATES OF LESS THAN A
MILLION AND 550 PATIENTS THAT
WILL BE WORLDWIDE WITH A
PARTICULAR DISEASE AND WELL
DEFINED PATHWAYS GIVING IDEAS
WHERE TO TREAT MANY IMMUNE
CYTOKINES THAT IS INTERFERON
IL18 AND HYPOACTIVATION AND
MODIFIERS OF AUTO IMMUNE
RESPONSES AND PATIENTS ARE
SPREAD THROUGHOUT THE WORLD AND
WE HAVE INCREDIBLE OPPORTUNITY
TO RECRUIT THEM AND FORM COHORTS
OF PATIENTS NEEDED TO MAKE
CLINICAL OBSERVATIONS PHENOTYPE
OF DISEASE AND DO BASICALLY
TREATMENTS AND HOWEVER OUT OF
THE 73 GENETICALLY DEFINED AUTO
INFLAMMATORY DISEASES SYSTEMIC
WE HAVE DRUGS APPROVED FOR FIVE
OF THOSE DISEASES AND ABILITY TO
DISCOVER THOSE DISEASES FAR
OUTSPACES OUR ABILITY TO APPROVE
TREATMENTS BASICALLY.
TREATMENT IS IMPORTANT.
PATIENTS PRESENT WITH SYSTEMIC
AND ORGAN INFLAMMATION THAT
LEADS TO RAPID DEVELOPMENT AND
PROGRESSION OF ORGAN DAMAGE
DISABILITY AND MORTALITY FOR
MANY DISEASES IS AROUND 30% IN
ADOLESCENTS BEFORE THEY HIT
CHILDHOOD AND ORGAN DAMAGE
EFFECTS ORGANS WE SEE HERE AND
TREATMENT APPROACHES ARE
CURRENTLY TARGETED TO BLOCK
INFLAMMATION.
THERE ARE GREAT OPPORTUNITIES TO
ACTUALLY IN THE FUTURE POSSESS
DRUGS EFFECTING PATHWAYS WITH
IMPACT ON TISSUE DIFFERENTIATION
THAT DERIVE ORGAN DAMAGE.
I WAS ASKED BY DEDETO TELL YOU
ABOUT TWO SUCCESS STORIES OF
GETTING DRUGS APPROVED FOR TWO
RARE DISEASES THAT I HAVE --
THAT I HAVE HEADED OR HAVE LED.
ALSO, TO BASICALLY POINT TO THE
BUMPS THAT WE HAVE. THE FIRST
DISEASE IS ACTUALLY A DISEASE
THAT IS NEONATAL ONSET SYSTEM
DISEASE THAT I HAVE BEEN
STUDYING AND HAVE
[INDISCERNIBLE] OF IN 2000 AND
HAVE IDENTIFIED THE GENETIC
CAUSE FOR FAMILIAL DISEASE THAT
PRESENTS WITH CODE INDUCED
FEVERS AND NEUTROPHILIC
DECARRIER AND IN TWO YEARS WE
USED ACTUALLY GENE AND SEARCH
PRIOR TO EX-HOME GENOME
SEQUENCING TARGETED APPROACH AND
SEVERE PHENOTYPE THAT PRESENTED
WITH FEVER AND NEUTROPHILIC
CARRIER AND LED TO RAPID
PROGRESSION PRESENTED WITH
ANJIETS AND HEARING LOSS AVEND
MUSCULAR DISTROPHY AND FINDING
OF MUTATION AT THAT TIME
COINCIDED WITH DISCOVERY THAT
THIS MOLECULE IS ASSOCIATED WITH
IL1 ACTIVATING PATHWAY THAT IS
INFLAMOSOME AND RAISED QUESTION
WHERE I1 IS DRIVING A MAJOR
COMPONENT OF DISEASE PHENOTYPE
WE SEE IN THOSE PATIENTS AND
RARER DISEASE AFTER THAT, WE
IDENTIFIED LOSS OF FUNCTION
MUTATIONS AND PATIENTS
PRESENTING WITH PUFTULA SKIN
LESIONS AND AFTO MILITIS AND
LACK OF IL1 RECEPTOR ANTAGONIST
MADE INTO RECOMBINANT MEDICATION
SOLD AND MARKETED AND THAT DRUG
HAS BEEN AVAILABLE AND LED TO
THE DEVELOPMENT OF TRANSLATIONAL
STUDY USING [INDISCERNIBLE]
RECOMBINANT IL1 RECEPTOR
ANTAGONIST TO TREAT PATIENTS
WITH NO. NOMAD AND MAJOR
RESPONSES WE HAVE SEEN MADE
CLEAR THAT IL1 HAD A MAJOR ROLE
IN THAT AND WROTE A
TRANSLATIONAL PROTOCOL AND AT
THAT TIME NEGOTIATIONS WITH MGEN
WHO MARKETED MEDICATION APPROVED
FOR TREATMENT OF RHEUMATOID
ARTHRITIS FAILED APPROVAL INCEP
SIS AND INTELLECTUAL PROPERTY
RIGHTS IT COULD NT BE SIGNED AND
COULD CO-REFERENCE IND AND NIH
PHARMACY AGREED TO PURCHASING
AKINRA. WE WERE ABLE TO CONDUCT
STUDY AND DO OBSERVATIONS BUT
NOT WITH SUPPORT THAT WE
INITIALLY HOPED TO GET AND HAD
TO GENERATE ACCESS DATA BASE
BECAUSE CASE REPORT FORMS COULD
NT BE ENTERED INTO COMPANY DATA
BASE THAT WE INITIALLY ACTUALLY
HOPED FOR.
IT WASN'T AVAILABLE.
ROAD GOT BUMPIER AND GOT TO FDA
APPROVAL AFTER 10 YEARS AND
THERE WERE SEVERAL
MODIFICATIONS.
AND SEVERAL HEADACHES.
AFTER THE DRUG HAD BEEN VERY
BENEFICIAL TO PATIENTS, PARENTS
GOT VERY CONCERNED ABOUT
CONTINUED ACCESS AND
PARTICULARLY IN THE CONTEXT WHEN
RIGHTS OF AKIN RA WAS SOLD TO
SOBY IN 2008 AND NO INDICATION
FOR INCREASING INDICATION OF
OBTAINING APPROVAL AND WHAT IS
HEARD AND IF TOLD IF DRUG IS
ALREADY APPROVED WHY NOT GET IT
OFF LABEL?
FAMILY OF ORGANIZATION OR AUTO
INFLAMMATORY ALLIANCE CONDUCTED
STUDY TO ASK WHICH PATIENTS BY
2008 WERE ABLE TO GET THE DRUG
THROUGH INSURANCE THAT IS LESS
THAN 50% WERE ABLE TO GET DRUG
THROUGH INSURANCE AND EXTENDED
STUDY MULTIPLE TIMES TO SUPPLY
DRUG FOR PATIENTS AND WERE ABLE
TO GENERATE A CREEDA WITH SOBY
AND SOME RIGHTS AND RESTRICTIONS
AND PATENT OR LICENSE WAS
TRANSFERRED OR REMOVED AND BASED
ON CONTINUED PUSHING FROM THE
FAMILY ORGANIZATION THAT WROTE
LETTERS AND SOBY AGREED TO
FILING AN OR FAN DESIGNATION TO
AKIN RA AND SUPPORT THE
SUBMISSION OF THE DATA THAT WE
ACTUALLY HAD COLLECTED AND THAT,
AGAIN, WBUMPY AGAIN AND FDA AND
SOBY FILED APPLICATION SPENT
MONTHS AT NIH CLEANING DATA
GETTING IT IN DATABASE THAT
WOULD BE ACCEPTABLE FOR
REGULATORY ADMISSION AND FALL OF
2011 FAILED AND FDA FELT THAT WE
NEEDED A RANDOMIZED CONTROL
STUDY TO APPROVE EFFICACY THAT
LED TO AN AN APPEAL BY THE
COMPANY AND FDA INVITED THE
PANEL THAT CONSISTED OF EXPERTS
IN THE FIELD AS WELL AS PATIENTS
AND PARENTS AND AFTER THAT,
DECIDED ON THE FACT THAT OUR
DATA WAS SIGNIFICANT AND WAS
SUFFICIENT FOR APPROVAL THAT
RESTED ON FACT THAT WE HAD
CONVERTED A RANDOMIZED CONTROL
STUDY THAT WE COULDN'T DO WITH
ADDING AN OPEN LABEL WITHDRAWAL
STUDY FOR PATIENTS.
WHAT WE SAW WAS WITHIN THREE
MONTHS PATIENTS NORMALIZE THEIR
SYMPTOMS AND INFLAMMATORY
MARKERS.
WHEN WE WITHDREW PATIENTS AFTER
THREE MONTHS AND 2 TO 5 DAYS
THEY HAD REBOUND FLAIRS AND
SYMPTOMS REOCCURRED AND
INFLAMMATORY MARKERS WERE HIGHER
THAN THEY WERE AT BASELINE AND
WE WERE WORRIED ABOUT PERMANENT
ORGAN DAMAGE AND STOPPED THE
TRIAL OR ARM OF THE STUDY THAT
IS BEING NOT ETHICALLY
SUPPORTABLE AFTER 11 PATIENTS
HAD BEEN WITHDRAWN.
THAT COMPONENT WAS LATER DECIDED
TO BE UNETHICAL GIVEN SEVERITY
OF THIS DISEASE THAT ACTUALLY
ALLOWED THE APPROVAL OF THE
STUDY AND APPROVAL OF THE DATA
AND MADE A HUGE DIFFERENCE IN
FACT TO CHILDREN WITH THIS
DISEASE.
NOW THEY WEREN'T IN FACT ABLE TO
OBTAIN THE DRUG THROUGH THE
INSURANCE.
AND THE -- ALTHOUGH AKINRA WAS
REPURPOSED IT WAS APPROVED FOR
RHEUMATOID ARTHRITIS AND
[INDISCERNIBLE] TO OTHER
STRATEGIES TO PLOT IL1
RECOMBINANT IL1 RECEPTOR AND
ANTIBODY FOR BETA WE WERE
AVAILABLE AND NOT APPROVED IN
CONTEXT OF AGENTS BEING
SUCCESSFUL AND COMPANIES
ACTUALLY ADDRESSED US AND GOT
RARE OR FIRST APPROVAL IN A RARE
DISEASE THAT IS UNUSUAL TO
OBTAIN DRUG FOR PATIENTS WITH
RARE DISEASES WITHOUT APPROVAL
AS YOU HAVE HEARD IS A CONSTANT
BATTLE AND WORKS SOMETIMES AND
ALLOWED US TO ACTUALLY CONSIDER
[INDISCERNIBLE] A LONGER ACTING
IL1 INHIBITOR FOR SECOND
DISEASE.
WE CONVINCED INITIATOR STUDY
SUPPORTED DRUG AT BEGINNING TO
TREAT PATIENTS WHO BASICALLY HAD
BEEN TREATED WITH ANAKINRA AND
FDA HEARING PRESENTATION ABOUT
DISEASES THAT ENCOURAGED
REGENERAL RANT TO FILE A
SUPPLEMENT ALIBI LOGICAL LICENSE
APPLICATION FOR RELONO CREPT FOR
INDICATION DIRA THAT CONSIDERED
AND ACTUALLY AFTER A BRIEFING
DOCUMENT WITH FDA AND FOUND THAT
ALL PATIENTS PREVIOUSLY HAD BEEN
TREATED WITH ANAKINRA WOULD
CONSIDER CO-FILING TO INDUCE
REMISSION AND [INDISCERNIBLE] TO
MAINTAIN REMISSION IN DISEASE
WHERE WE HAD LITERALLY AGAIN AN
AMAZING RESPONSE TO TREATMENT
AND PATIENTS WERE ACTUALLY
LACKING OR MAKING PROTEIN IL1
RECEPTOR ANTAGONIST THAT AKINRA
WAS A REPLACEMENT AND TREATMENT
WITH RELONOCEPT WORKED WITH
DAILY INJECTIONS THAT ARE
PAINFUL AND CHALLENGING FOR
PATIENTS AND TOOK A WHILE TO
DWET SOBY TO CONVINCE TO FILE
FOR A RARE DISEASE AND NIH AND
ACTUALLY DIET ALLOWED ME TO HIRE
A ZERO TO CLEAN DATA THAT WAS
COLLECTED ON A NATURAL HISTORY
STUDY AND HAD TO BE PULLED OUT
RETROSPECTIVELY TO GENERATE DATA
CLEAN ENOUGH TO BE CONSIDERED
FOR REGULATORY SUBMISSION AND
AGREED TO FILING REGULATORY
COMPONENT COULDN'T BE TAKEN OVER
BY INVESTIGATORS HAD TO BE DONE
BY COMPANY AS WELL AS WRITING
THE LABEL AND 2020FDA APPROVES
ANAKINRA AND [INDISCERNIBLE] FOR
TREATMENT OF [INDISCERNIBLE] AND
AFTER 13 YEARS AND 7 YEARS OF
USING AN IL1 TRIAL AND ACTUALLY
ENROLLING PATIENTS IN THE
NATURAL HISTORY STUDY AND ALSO
SHOWED THAT DATA COLLECTED IN
PROSPECTIVE WAY IN NATURAL
HISTORY STUDY COULD BE USED FOR
DRUG APPROVAL BASED ON DATA IN
PATIENTS RECEIVING AKINRA AND
RECEIVED [INDISCERNIBLE] AND
STUDIES WERE OPEN LABELED AND
USING HISTORICAL DATA WE COULD
SHOW ALL PATIENTS BEING REPORTED
WITH DIRA AND RETROSPECTIVELY
DIAGNOSED DIDN'T SURVIVE AND
DIED MEDIAN YEARS AND PROLONGED
HOSPITALIZATION AND WE USED
HOSPITALIZATION DATES AS WELL AS
HISTORICAL DATA ON DEATH AND
MORTALITY TO F- ACTUALLY GET
OPEN LABEL DRUG APPROVED AND
WERE LESS SUCCESSFUL WITH
ANOTHER CONDITION THAT WE
IDENTIFIED IN 2011 AND LOSS OF
FUNCTION MUTATIONS IN
PROETEOSOME CAUSE INFLAMMATORY
DISEASE PRESENTING WITH
NEUTROPHILIC PANNO CHOELITIS AND
FAT WITH METABOLIC SYNDROME AND
PATIENTS HAD STRONG INTERFERON
SIGNATURE SUGGESTING THAT IT
MIGHT BE A LARGE DRIVER THAT IS
SUPPORTED BY BASIC RESEARCH
FINDINGS IN DRIVING DISEASE
MANIFESTATIONS AND IN 2011,
MARKETED BY ASTROZEN EBBINGA WAS
ON THE MARKET. WEREN'T TO
DEVELOP OR OBTAIN THAT.
WASN'T APPROVED FOR THE DISEASE.
IT WAS ACTUALLY IN TRIALS FOR
LUPUS AND BECAUSE THE DISEASE
WAS QUITE SIGNIFICANT AND
ACTUALLY CAUSES SEVERE GROWTH
RETARDATION IN CHILDREN AND
BLOCKING INTERFERON SIGNALING
FROM LILY DRUG WAS NOT APPROVED
AT THAT TIME FOR RHEUMATOID
ARTHRITIS AND THEY MADE IT
AVAILABLE.
THIS WAS LUCKY AND TREATMENT
IMPROVED DISEASE SIGNIFICANTLY
AND LED TO COMPLETE REMISSION OF
STEROIDS IN 50% OF PATIENTS
DEVELOPING BIOMARKET TO QUANTIFY
MEASURING INTERFERON SIGNALING
NORMALIZING 50% OF PATIENTS WITH
CANDLE LONG TERM AND AFTER
ENCOURAGING APPROVAL OF DRUG FDA
DECIDED IN 2021 NOT TO APPROVE
THE OPEN LABEL DATA STUDY WAS
EXPANDED IN ACCESS PROTOCOL AND
EXPANDED IN NOVEL DISEASES LATER
AND AS SUGGESTION WAS THAT WE
HAD INSUFFICIENT DATA TO SUPPORT
OR INADEQUATE DATA TO SUPPORT
RISK BENEFIT RATIO AND WE NEEDED
HIGHER DOSES THAT HAD BEEN USED
OR HIGHER EXPOSURE THAN ACTUALLY
HAD BEEN USED FOR RHEUMATOID
ARTHRITIS AND CONCERNS ABOUT
SIDE-EFFECTS AND TREATMENT IS
APPROVED OR RECOMMENDED BY
EXPERTS THAT IS ONLY AVAILABLE
TREATMENT MAKING MAJOR IMPACT ON
THIS OTHER RARE DISEASE.
WE NEED TO BASICALLY OBTAIN IT
OFF LABEL.
SO, I THINK I HAVE BEEN TRYING
TO SHOW THAT WE CAN MAKE
DIFFERENCES.
THESE DISEASES ARE OFTEN MODELS
FOR DRUG DEVELOPMENT AND PATHWAY
IS DEFINED AND IS VERY SPECIFIC
AND CLINICAL DISEASE
MANIFESTATIONS OR ORGAN
MANIFESTATIONS ARE DISEASE
SPECIFIC AND TARGETED TREATMENTS
USING CONDITIONS ALLOW FOR PROOF
OF MECHANISM AND VALIDATION OF
BIOMARKERS OPTIMIZING DOSING AND
IN FACT WE CAN ENROLL PATIENTS
OR CONTINUE TO ACTUALLY SEE THEM
EITHER LONG-TERM OR ENROLL THEM
BACK ON NATURAL HISTORY STUDY
AND LOOK AT IMPACT OF
MODIFICATIONS OF ORGAN DAMAGE
LONG-TERM AND PROVIDE PROOF OF
CONCEPT THAT BLOCKING A SPECIFIC
MECHANISM HAS AN IMPACT ON
DISEASE MANIFESTATIONS AND WE
HAVE TO CHANGE TRAJECTORY OF
DRUG APPROVALS OF ULTRA RARE
DISEASES MAKING IT FASTER AND
CHALLENGES TO TACKLE AND
PARTNERSHIPS WITH FDA AND
PRIVATE SECTORS AND PHARMA-AND
NIH WILL GET US TO TEARING DOWN
BARRIERS RISK AVERSION BY
PHARMACEUTICAL COMPANIES TO MAKE
DRUGS AVAILABLE FOR PATIENTS
WITH RARE DISEASES AND
TRADITIONAL HAVE NO GOOD FILE
DESIGN TRADITIONAL DESIGNS
WORKING THROUGH FOUR PHASES
DON'T WORK AND PARTICULARLY NOT
ULTRA RARE DISEASES
RANDOMIZATION IS NOT POSSIBLE OR
NOT ETHICAL.
WE HAVE TO WORK WITH REGULATORY
AGENCIES TO DEFINE OUTCOMES THAT
COULD BE RECOGNIZED FOR
REGULATORY APPROVAL.
WE HAVE TO DEFINE ECRFS AND
IDENTIFY AND MEASURE OUTCOMES IN
NATURAL HISTORY STUDIES.
WE HAVE TO OVERCOME
LOGISTICS AND GIANT LOGISTICS
THAT PATIENTS ARE DISTRIBUTED
GLOBALLY THAT IS IMPORTANT TO
FORM GLOBAL NETWORKS THAT WE
HAVE ACTUALLY STARTED TO DO AND
THIS IS A PROBLEM THAT NEEDS TO
BE GLOBALLY ADVANCED.
GENERATED UP TO PLATFORM TRIAL
DESIGNS ALLOWING US TO ADD
DISEASES AND TREATMENTS WITHOUT
HAVING TO GO THROUGH PROTOCOL
DEVELOPMENT DEVELOPING MODULAR
OUTCOMES LONGITUDINALLY THAT
COULD BE ASSESSED AND TALKING
ABOUT COLLABORATIONS AND
DEVELOPING A CLINICAL TRIAL
INFRASTRUCTURE AT NIH THAT
ALLOWS ALSO TO SHARE DATA FROM
CLINICAL TRIALS GENERATED
INTRAMURALLY WITH
[INDISCERNIBLE] AND PREPARING
THEM EASILY FOR REGULATORY
SUBMISSION.
WITH THAT, I AM GOING TO STOP
HERE.
I HAVE NOSTALGIC SLIDES I HAVE
TO SHOW YOU.
TAKES A VILLAGE TO DO THAT AND
WORK AND REGULATORY WORK WAS
DONE ACTUALLY BY PEOPLE AT NIH
AND NORISSA'S DEALT WITH DATA
MANAGEMENT AND WITH THE CURRENT
TEAM.
THANK YOU VERY MUCH.
>> THANK YOU VERY MUCH.
YEAH. YOU KNOW, LISTENING TO
YOU, THERE CAN'T BE A BUSINESS
MODEL FOR DEVELOPING THESE
DRUGS.
PHARMACOMPANY HAVE ENGAGED IN
THAT FOR A DIFFERENT REASON.
THIS IS A SOCIETAL MODEL NOT
ONLY FOR SUFFERING THAT FAMILIES
ARE EXPERIENCING AND FOR COST
THAT UNTREATED DISEASES
ACCUMULATE AND MAYBE ENGAGEMENT
OF PAYERS IS REASONABLE AND THE
END TREATING THE DISEASES NOT
JUST ALLEVIATING SUFFERING AND
IS LESS COSTLY THAN TREATING
PATIENTS.
PETER IS THE NEXT SPEAKER.
THANK YOU, PETER.
>> HI. THANK YOU FOR INVITING
ME TODAY.
I'M PETER AND VICE PRESIDENT OF
CLINICAL DEVELOPMENT AT INSIGHT
AND TRAINED AS A PEDIATRIC
HEMATOLOGIST AND ONCOLOGIST AND
HAVE BEEN IN INDUSTRY FOR 20
YEARS OR SO WORKING ACROSS
DIFFERENT NUMBER OF COMPANIES
AND APPRECIATE PRESENTATIONS
COMING BEFORE IN THIS SESSION
AND DURING THE DAY TALKING ABOUT
VALUE OF COLLABORATION AND
PUBLIC AND PRIVATE FDA
COLLABORATION AIT IS IMPORTANT
WE DON'T HAVE TIME AND RESOURCES
TO DO EVERYTHING OR ALL OF THE
IDEAS AND MANY IDEAS OUT THERE
HAVE TO BE EXPLORED AND CAN BE
THROUGH COLLABORATIONS.
I WANT TO HIGHLIGHT IN INTEREST
OF TIME EXAMPLES WHERE PROJECTS
WORKED ON AND PHARMACEUTICAL
COMPANY HAD PRIORITIZATION OF
INDICATIONS AND COLLABORATIONS
EXTERNALLY AND THROUGH NIH THAT
WE WERE ABLE TO PROVIDE
TREATMENTS FOR PATIENTS WITH
RARE DISEASES FOR DISEASES THAT
DIDN'T HAVE AVAILABLE TREATMENTS
AND NIH IS REALLY CRITICAL IN
SUPPORTING THAT DEVELOPMENT.
FIRST [INDISCERNIBLE] IS A DRUG
BEING DEVELOPED THAT IS A DRUG
THAT IS BEING DEVELOPED FOR A
NUMBER OF CANCERS AND LUNG
CANCER THAT IS INTERESTED IN AND
COLLABORATION WITH RESEARCH LABS
LOOKING AT TARGETS THIS DRUG
MIGHT HAVE AND ONE LAB LOOKED AT
DRUGS ROLE IN EPIDERMAL GROWTH
FACTOR RECEPTOR INHIBITION.
FRIEND IN LAB SAID I'M LOOKING
AT RED ONCHA GENE AND HE GAVE
SOME IT WAS AN INHIBITOR OF
RECEIPT ON KA GENE THAT IS AKEY
DRIVER IN THOSE WITH MEDULLARY
CANCER WHICH IS A RARE CONDITION
AND AT TIME NO AVAILABLE
TREATMENTS SOMEONE AT NIH EXPERT
IN THIS CANCER AND SAW
PRECLINICAL DATA SHOWING THIS
AND BEING AT NIH CENTER FOR
EXCELLENCE AND HE BEING AN
EXPERT INITIATED A PILOT STUDY
AND SHOWED IN THE FIRST JUST
HANDFUL OF PATIENTS A NUMBER OF
GOOD RESPONSES AND IN PATIENTS
AND ULTIMATELY THE COMPANY
DECIDED TO DO A REGISTRATION
STUDY AND HAD CONVERSATIONS WITH
FDA AROUND THE DESIGN OF THIS.
IT IS IMPORTANT WE DON'T OPERATE
IN A VACUUM AND HAVE DISCUSSIONS
WITH EXPERT PHYSICIANS WITH FDA
AND PATIENTS WHAT IS MEANINGFUL
AND RELEVANT ENDPOINT STUDY
DESIGN AND AS A COMPANY DID
REGISTRATION STUDY AND NIH
POSITION WAS LEAD INVESTIGATOR
ON THAT AT THE TIME.
THAT ENDED UP BEING AN
INDICATION FOR THE DRUG THAT
BECAME AVAILABLE FOR THIS RARE
TYPE OF THYROID CANCER.
THE OTHER EXAMPLE I WILL MENTION
THAT IS AN INTERESTING CASE THAT
IS A DRUG ALTROMBAFAG A GROWTH
FACTOR SUPPORTING DEVELOPMENT OF
BLOOD PLATELETS AND WAS BEING
DEVELOPED FOR A COUPLE
INDICATIONS WITH THE COMPANY.
AND WE WERE CONTACTED BY THE NIH
BY A PHYSICIAN AT NIH ONE OF THE
WORLD'S EXPERTS IN APLASTIC
ANEMIA THAT, AGAIN, NOT A LOT OF
TREATMENTS AVAILABLE SHORT OF
BONE MARROW TRANSPLANT AND NOT
EVERYONE HAS A DONOR AVAILABLE.
MANY PEOPLE WOULD USE
HEMATOPOIETIC GROWTH FACTOR AND
NUMBER OF THESE WERE AVAILABLE
AND DIDN'T WORK AND THEY WERE
PRETTY EXPENSIVE AND PEOPLE
WOULD TRY THEM AND GIVE THEM FOR
A LONG PERIOD OF TIME AND THEY
DIDN'T WORK AND INTERESTINGLY
PHYSICIAN AT NIH CONTACTED US
AND WANTED TO DO A STUDY TO
PROVE THAT IT DID NOT WORK FOR
APLASTIC ANEMIA.
THIS IS PROBABLY NIH IS THE ONLY
PLACE YOU COULD DO THIS STUD.
YOU KNOW MOST PHYSICIANS AND
PHARMACEUTICAL COMPANIES WON'T
DO A STUDY TO PROVE A DRUG
DOESN'T WORK.
WE SAID FINE. WE HAD NO
SPECIFIC INTERESTS IN APLASTIC
ANEMIA AND IF THIS WOULD HELP
PATIENTS AND PHYSICIANS
UNDERSTAND HOW BEST TO TREAT IT
WE WILL DO IT AND IT TURNED OUT
THAT THE DRUG WORKED FOR
APLASTIC ANEMIA.
SO, THE NIH CONDUCTED A FAIRLY
EXTENSIVE STUDY SINGLE ARM STUDY
DIDN'T HAVE CONTROL GROUP
RELATIVELY RARE CONDITION AND
GENERATED ENCOURAGING DATA THAT
FROM THE NIH STUDY ENDED UP
SUPPORTING FDA APPROVAL FOR
APLASTIC ANEMIA.
THERE ARE DIFFERENT WAYS THAT
COLLABORATIONS CAN WORK AND YOU
CAN HAND OVER ENTIRE DRUG IF
PHARMACOMPANY HAS NO INTEREST IN
DRUG AND HAND OVER DRUG TO NIH
AND LET THEM GO WITH IT AND HAND
OVER A PORTION OF THE
DEVELOPMENT IF INDICATIONS ARE
RARE WHERE NIH HAS PARTICULAR
EXPERTISE AND TRANSLATIONAL
SCIENCE THAT WAS TALKED ABOUT
BEFORE AND HANDING OVER PARTS OF
DEVELOPMENT THERE AND YOU CAN
GET FDA APPROVAL THROUGH NIH
COLLABORATIONS AND COMPANY
SPONSORED TRIALS WITH KEY
INVOLVEMENT OF NIH EXPERTS OR IN
CASE OF APLASTIC ANEMIA THAT IS
APPROVAL BASED SOLELY ON STUDIES
DONE AT NIH.
I WILL CLOSE THERE.
I WILL SAY THAT THERE ARE
OBSTACLES AT PHARMACEUTICAL
COMPANIES AND CLEARLY THERE ARE
CONCERNS IF YOU GO INTO NEW
INDICATION YOU WILL GET FINDINGS
THAT ADVERSELY EFFECT APPROVED
INDICATIONS AND SAFETY PROFILE
AND QUESTIONS AROUND RESOURCES
INVOLVED AND OPPORTUNITIES FOR
EXPANDING INDICATIONS THAT ARE
PARTICULARLY IN RARE DISEASES
OFTEN AT NIH CENTERS FOR
EXCELLENTS AND PATIENTS AROUND
THE WORLD COME THERE AND
OPPORTUNITY FOR US TO EXPLORE
NEW INDICATIONS AND PROVIDE
VALUE FOR PATIENTS AND NEW
OPPORTUNITIES FOR THERAPEUTICS.
I'LL PAUSE THERE. I CAN TAKE
QUESTIONS FOR LATER.
>> I WAS LAUGHING AND SAID
CLINICAL TRIAL AND INDEED IS
POSSIBLE AT NIH AND WILL TAKE
SERIOUSLY IN THIS KNOWLEDGE
ASPECT OF DISEASES.
IT IS -- IT IS VERY FRUSTRATING
WHEN PHARMACEUTICAL COMPANIES
ABANDON DRUG WITHOUT
UNDERSTANDING WHY IT DIDN'T WORK
UNDERSTANDING IS ESSENTIAL FOR
DEVELOPMENT OF BETTER DRUGS THAT
IS WHAT WE DO AT NIH CLINICAL
CENT
CENTER.
RAPH
RAPHAELA PRESENTATION NOT ALL
NIH IS UNIQUELY PHENOTYPED AND
LEVEL OF MEASUREMENTS AND
PHENOTYPING OF DISEASE THAT IS
INTRAMURAL RESEARCH PROGRAM IS
UNPRECEDENTED AND BEEN AT
UNIVERSITY AND IT IS
UNPRECEDENTED.
YEAH. I THINK THAT IS ONE OF
THE REASONS WE WANT TO REALLY
ORGANIZE THIS MEETING BECAUSE I
THINK THAT A LOT OF -- A LOT OF
DRUG COMPANIES DON'T UNDERSTAND
HOW UNIQUE THIS ENVIRONMENT IS
FOR -- THANK YOU.
THIS IS DEFINITELY SOMEBODY THAT
UNDERSTANDS AND HAS BEEN AT NIH
AND IS AT THERAPEUTICS.
PLEASE.
>> AS DEDIMENSIONED I'M A
PHYSICIAN SCIENTISTS PREVIOUS
INVESTIGATOR AT NIH WITH
RESEARCH FOCUS AT T-CELL
PATHOGENESIS AND INFORMATION
THAT IS FUNDAMENTAL INFLAMMATION
IN MOST ALLERGIC DISEASES AND
ASTHMA WORKED ON PROJECTS TO
REPOSITION AND APPROVE DRUGS
WON'T GET INTO THAT AND LEFT NIH
IN 2016 AND JOINED A SMALL
COMPANY AND NOT BIOSCIENCES TO
DEVELOP A DRUG DRAMA PRAMA
PECHLEL STORY THAT I WILL
BRIEFLY TELL YOU WITH DRUG
REPURPOSING NEW INDICATIONS AND
ALSO VERY MUCH INVOLVING
ACADEMIC INDUSTRY COLLABORATION
AND COLLABORATIONS WITH NIH AND
ALSO INTERESTINGLY WITH ANJAN
AND SIMON ON THIS PANEL.
STRONG NEUROSCIENCE RUNNING
THROUGH WITH ALS AND
PARKINSON'S.
PRAMA PECHLEL IS AN APPROVED
DOPAMINE AGONIST DRUG USED IN
TREATMENT OF PARKINSON'S DISEASE
AND YEARS BACK INVESTIGATORS
FOUND IT WAS NEUROPROTECTIVE
AGAINST OXIDATIVE STRESS HAVING
CLINICAL ACTIVITY AND
NEUROPROTECTIVE DISEASES AND
CONCENTRATIONS REQUIRED WOULD BE
TOXIC BECAUSE OF DOPAMINE
ACTIVITY AND JAMES AT UVA
HYPOTHESIZED THAT RIGHT-HANDED
ANAN TOMORROWER DECHL OR
DEPROEPO PECHLEL WOULD HAVE THIS
EFFECT AND NOT DOPAMINE TOXICITY
AND WAS RIGHT AND DID EARLY
PILOT INVESTIGATIONS AND
PARKINSON'S AND ALS AND LICENSED
DRUGS TO SMALL
BIOPHARMABIOSCIENCES AND WENT
FORWARD WITH CLINICAL
DEVELOPMENT WITH PROOF OF
CONCEPT PHASE 2 STUDY IN ALS
THAT WAS SUCCESSFUL AND PHASE 3
OF FAILED TO REPLICATE PRIMARY
ENDPOINT AND DURING CLINICAL
DEVELOPMENT THEY NOTICED THAT IT
LOWERED EO SINOFILL ACCOUNTS AND
SAME TIME ANTI-IL5 BIOLOGICS
WERE SHOWN TO EFFECTIVELY TREAT
ASTHMA BY LOWERING EO SINOFILL
ACCOUNTS AND IT IS A SMALL
MOLECULE TAKEN ORAL LY
THERAPEUTIC ADVANCE AND PIFR
OTED DEVELOPMENT TO
[INDISCERNIBLE] DISEASES AT
WHICH POINT THAT IS WHEN I
JOINED AND WE COMPLETED A
CLINICAL PROOF OF CONCEPT STUDY
IN [INDISCERNIBLE] SYNDROME PART
OF COOPERATIVE RESEARCH AND
DEVELOPMENT AGREEMENT WITH AMY
CLEEON AT NAEID AND LATER
COMPANY I HEADED UP A PHASE 2
PROOF OF CONCEPT TRIAL AND IT
WAS SUCCESSFUL. WE ARE IN PHASE
3 OF THE DRUG.
LOTS OF REPURPOSING AND SORT OF
WHAT -- YOU KNOW, TRYING TO FIND
WHERE DOES THIS DRUG HAVE A HOME
IN TERMS OF TREATING DISEASE
THAT HAS GONE ALONG THE WAY AND
THINK THAT REALLY RIGHT NOW
SEEING THE FRUIT OF THAT IN
PHASE 3 TRIALS.
I WILL STOP THERE FOR INTEREST
OF TIME.
I WILL JOIN THE DISCUSSION
LATER.
>> THANK YOU VERY MUCH.
LAST SPEAKER IS SIMON.
SIMON SCOTT.
HE IS FROM THE FRON PROFIT
SECTOR WITH AN INTERESTING STORY
TO SAY.
>> THANK YOU I'M SIMON AND
DIRECTOR THAT IS WITH A RESEARCH
CHARITY IN THE UK AND FUND
RESEARCH INTERNATIONALLY
PRECLINICAL AND CLINICAL FOCUSED
ON DISEASE MODIFICATION FOR
PARKINSON'S AND BEEN WITH THE
ORGANIZATION FOR FIVE YEARS AND
BEFORE THAT DID IDEAS OF
RESEARCH IN ACADEMIC AND BIOTECH
RESEARCH IN LAB AND CLINICAL AND
ORGANIZATION WAS FOUNDED IN 2005
BY FOUR JA GENTLEMEN FOCUSED ON
LACK OF RESEARCH IN ACTUALLY
CURING THE CONDITION AND IN 2011
WHEN THEY FOUND THEIR FEET THEY
INITIATED TRIALS PROGRAM ILCT
STARTING OUT AT DRUG REPURPOSING
PROGRAM THAT TOOK INSPIRATION
FROM NIH SYNAPSE PROGRAM IN
2003.
THIS WAS THE COMMITTEE TO
IDENTIFY NEOPROTECTIVE AGENTS
FOR PARKINSON'S AND EMPHASIS WAS
TO HAVE AN INTERNATIONAL
COMMITTEE OF PARKINSON'S EXPERTS
AND MEET EVERY YEAR WITH PURPOSE
OF EVALUATING MOLECULES WITH
EVIDENCE OF DISEASE FOR
MODIFICATION OF PARKINSON'S
ACCELERATING THEM INTO CLINICAL
TRIALS AND INVOLVES A TWO-DAY
FACE-TO-FACE MEETING THAT IS
HELD IN LONDON OR GRAND RAPIDS
MICHIGAN WITH PARTNERS VAN
HANDLE INSTITUTE AND BASIC AIM
IS TO DEBATE EVALUATE AND RANK
AND PRIORITIZE A SET OF DOSSIERS
WE PRESENT TO THE COMMITTEE EACH
YEAR MADE UP OF 23 LEADING
EXPERTS IN THE WORLD AND ARE
BEST OF THE BEST AND WONDERFUL
PEOPLE AND PRESENT TWO WEEKS
BEFORE A MEETING WITH SET OF
DOSSIERS 15 TO 20 DOSSIERS, 20
PAGES EACH AND IN EACH WE HAVE
EVERYTHING WE KNOW ABOUT A
PARTICULAR MOLECULE THAT HAS
PRESENTED SOME EVIDENCE AND THEY
ARE WRITTEN IN HOUSE BY RESEARCH
TEAMS IN PARKINSON'S AND 2012
SINCE THEN 239 DOSSIERS
PRESENTED TO THE COMMITTEE
REPRESENTING TOTAL OF 171 AGENTS
NOT ALL ARE REPURPOSED MOLECULES
AND SO MUCH AGENCY YOU CAN
INCREASE AND LOOKING TOWARDS
CHEMICAL ENTITIES HOPING TO
ACCELERATE THEM TO THE CLINIC
AND PROGRAM ASSOCIATED WITH 20
COMPLETED TRIALS AND 21 ONGOING
STUDIES.
IN ADDITION TO PRIORITIZING
MOLECULES COMMITTEE HAS AVENUE
FOR FUNDING IF A MOLECULE IS
CONSIDERED NOT READY FOR PRIME
TIME TO GO TO A CLINICAL TRIAL
THEY CAN SEND IT BACK TO --
THROUGH A PROGRAM WE CALL ILTT
RESEARCH ACCELERATION PROGRAM
AND ASK RESEARCHERS TO -- TO DO
A PARTICULAR STUDY.
JUST WANTED TO GO THROUGH A
COUPLE OF EXAMPLES QUICKLY AT
THIS TIME.
ONE MOLECULE THAT IS PREVIOUSLY
BEING DISCUSSED HERE TODAY IS
GOP1 AGONISTS THAT IS SHOWING
ENCOURAGING DATA IN PARKINSON'S
AND TO CURE IT FUNDED AN EARLY
STUDY WITH THIS MOLECULE OR
EX-ENO TIED AND PHASE 3 CLINICAL
TRIAL COMING TO END IN FEBRUARY
OF THIS YEAR AND RESULTS OF THAT
COME IN MIDDLE OF THE YEAR AND
REPRESENTS A CHALLENGE IN TERMS
OF NEXT STEPS GOING TO
REGULATORS AND IF THE RESULTS
ARE POSITIVE.
BUT IF THE RESULTS ARE POSITIVE
IT ALSO REPRESENTS EXCELLENT
OPPORTUNITY AS AJ WAS SUGGESTING
IN TERMS OF POTENTIAL FOR
COMBINATION THERAPIES.
WE ALSO HAVE ANBROCHLEL WHICH IS
A RESPIRATORY MEDICATION
LICENSED IN EUROPE BUT NOT IN UK
OR AMERICA AND DRUG SCREENING
STUDY COMMON RISK FACTOR IS
[INDISCERNIBLE] AND SETTING UP
KAZ 3 CLINICAL TRIAL TO TEST IN
THE UK -- TAKING 21 PILLS A DAY
FOR 6 MONTHS ON TOP OF DOPAMINE
MEDICATION THEY WERE TAKING AND
HEROIC EFFORT IT IS A
[INDISCERNIBLE] TASTING PILL AND
REFORMULATED THAT DOWN TO THREE
PILLS A DAY.
BUT THIS IS ONE OF THE HURDLES
YOU FACE WITH DRUG REPURPOSING
OF COURSE AND MOLECULES
PRIORITIZED BY THE COMMITTEE
GOING INTO THIRD PARTY CLINICAL
TRIAL PLATFORMS FOR EXAMPLE
AUSTRALIAN PARKINSON'S
[INDISCERNIBLE] AND THREE ARMS
VERSUS PLACEBO AND IN UK SETTING
UP A PLATFORM FOR PARKINSON'S
CALLED EJS OR [INDISCERNIBLE]
ACCELERATING CLINICAL TRIALS OF
PARKINSON'S AT PD AND SOMETHING
TO KEEP AN EYE OUT FOR AND IF
INTERESTED IN OUR WORK WE HAD A
12 YEAR REVIEW MANUSCRIPT
CURRENTLY AT JOURNAL OF
PARKINSON'S PROVIETDING NOT ONLY
LESSONS WE HAVE LEARNED AND
SUMMARY OF MOLECULES THAT HAVE
BEEN NONCONFIDENTIAL MOLECULES
BEING EVALUATED BY THE COMMITTEE
AND BEYOND THAT I WILL STOP AND
SET ENOUGH AND WILL HAND IT BACK
TO DEDE.
>> THANK YOU VERY MUCH, SIMON.
OKAY. I THINK WE HAVE ALL
PANELISTS AVAILABLE.
AND I CAN SEE ONE QUESTION THAT
CHRISTINE ANSWERED IN CHAT AND
MAYBE CAN ANSWER IT HERE AND
QUESTION IS INTEREST OF PAYERS
MAKING GENERATIVE DRUGS
AVAILABLE FOR NEW USES AND
LARGEST US PAYERS ARE FEDERAL
AND STATE GOVERNMENTS.
IS THERE ANY THOUGHT FOR NIH TO
SUPPORT STUDIES WITH THE AIM TO
REDUCE DRUG COSTS FOR MEDICARE
AND MEDICAID?
>> IT IS A GREAT QUESTION THAT
I'M GLAD THERE IS SOMEBODY OUT
THERE WHO IS THINKING ABOUT CMS
AND THINKING ABOUT THAT
PERSPECTIVE THAT IS IN A
FANTASTIC POSITION PARTICULARLY
TO HELP US IDENTIFY EVEN, YOU
KNOW, WHAT ARE SOME THINGS THAT
ARE PARTICULARLY COSTLY TO THE
HEALTHCARE SYSTEM.
WE HAVE ACTUALLY SPOKEN WITH
THEM AND SPOKE WITH THEM A
NUMBER OF TIMES AND THERE ARE
SOME LIMITATIONS THAT WE RUN
INTO WITH PARTNERING WITH CMS
AND ARE LIMITATIONS IN TERMS
WHAT THEY ARE ABLE TO DO AND --
AND NOT DO.
THEY GIVE US A REALLY, REALLY
GOOD PERSPECTIVE FROM THAT --
YOU KNOW, PAYER -- THAT PAYER
SIDE OF THINGS.
WE HAVE SPOKEN WITH THEM ABOUT
IDEAS WHAT IT IS WE WANT TO DO
AND FROM A -- JUST FROM A
PERSPECTIVE IT MAKES SENSE TO
THEM AND WOULD BE WORTH PURSUING
AND IS HARD FOR THEM TO ENGAGE
DIRECTLY WITH US ON THINGS WE
WANT TO DO AND GREAT THOUGHT.
WE SPOKE WITH THE VA THAT HAS
OWN CLOSED ECOSYSTEM IN A WAY.
YOU HAVE RESEARCH CONDUCTED AT
VA AND AS WELL AS SEEING
PATIENTS AND OWN SORT OF PAYER
SYSTEM. WE SPOKE WITH THEM AND
IS ANOTHER PLACE IT MIGHT BE A
GOOD WAY TO PILOT STRATEGIES FOR
ENGAGING PAYERS.
>> OKAY. YOU KNOW, I THINK
PUBLIC VERY OFTEN TALKS ABOUT,
YOU KNOW, AI DESIGNING DRUGS.
IT DOESN'T SEEM TO ME THAT
BOTTLENECK IN DRUG DEVELOPMENT
IS DESIGNING A DRUG THAT ENGAGES
TARGET; RIGHT?
BOTTLENECK IS VALIDATING THE
TARGET THAT YOU HAVE RIGHT
TARGET AND DOING CLINICAL
TRIALS.
RIGHT?
SO S
SO, IN A PREVIOUS SESSION IT WAS
MENTIONED THAT SOMETIMES THE
WINNER DRUG IS NOT THE FIRST
DRUG.
IT IS THE BEST DRUG; RIGHT?
CLEARLY YOU KNOW ONE OF THE
ISSUES THAT -- THAT, YOU KNOW,
WE ALREADY DISCUSSED IS THERE IS
NOT ACTUALLY A BUSINESS MODEL
FOR THE PHARMATO -- TO REPURPOSE
DRUGS THAT ARE ALREADY PATENT
BUT MAY BE A BUSINESS MODEL OF
PROVING TARGET USING THESE
DRUGS; RIGHT?
SO, USING THAT, YOU KNOW, PROOF
OF PRINCIPLE TRIAL THAT SAYS
INDEED, YOU KNOW, THIS TYPE OF
ENGAGING THIS TYPE OF TARGET HAS
A POTENTIAL TO LIMIT THE
DISEASE.
THEN KIND OF OPEN IT FOR
PHARMATO COME UP AND DEVELOP
BETTER DRUGS.
SO, CAN YOU GUYS THINK ABOUT,
YOU KNOW, NON-PROFIT AND
GOVERNMENT?
WHO IS -- WOULD THERE BE A
SOLUTION FOR TESTING DRUGS THAT
MIGHT NOT HAVE ANY LONGER YOU
KNOW BUSINESS MODEL.
REALLY USING THEM FOR THIS LAST
STAGE OF KNOWLEDGE ACQUISITION
ABOUT HEALTH AND DISEASES AND
OPENING THAT VALIDATED TARGET
FOR PHARMA COMPANIES.
>> IF I CAN START A THING THAT
SOMEBODY MENTIONED EARLIER THAT
JUST PHARMA COMPANIES SHARING
ALL OF THE INFORMATION; RIGHT?
WHETHER DRUGS ARE SUCCESSFUL OR
NOT SUCCESSFUL, THE ABILITY AND
AVAILABILITY OF ALL THAT
INFORMATION COULD BE EXTREMELY
USEFUL TO A THIRD PARTY.
KRE
CERTAINLY, I WOULD SAY THAT THE
NIH HAS A VERY RESOURCE-RICH
ENVIRONMENT IN TERMS OF EXPERTS
AND PEOPLE AND COMPUTATIONAL
EXPERTS, ET CETERA.
AND, YOU KNOW, AT PHARMACEUTICAL
COMPANIES WE ARE SHARING PERHAPS
AFTER THE DRUG IS OFF PATENT
PERHAPS AFTER THEY FULLY
ADVANTED IT AND DEPOSIT
INFORMATION TO A THIRD PARTY
LOOKING AT OTHER INFORMATION AND
YOU WANT IT TO BE IN A SECURE
ENVIRONMENT THAT I THINK THAT
NEW DISCOVERIES COULD BE MADE
FROM THERE.
>> JUST ON TOP OF THAT IF IN
SOME WAYS INCENTIVIZES THAT
PROCESS.
>> ABSOLUTELY.
>> REGULATORY MASTER FILE AND
PRECLINICAL AND SAFETY DATA
AROUND PARTICULARLY THERE IS NOT
MUCH DOWNSIDE BUT IN SOME WAY TO
TRY TO INCENTIVIZE THAT PROCESS
FOR COMPANIES THAT I THINK ARE
ONE WAY TO FACILITATE THAT.
IT IS A TOUGH BOTTLENECK THAT I
ABSOLUTELY AGREE.
>> WE TALKED WITH CHRISTINE
BEFORE.
IF PEOPLE -- I -- I REALLY
DIDN'T KNOW A LOT OF THINGS
ABOUT PHARMA.
RIGHT?
IF YOU DON'T UNDERSTAND THOSE
REALITIES, YOU MAY COME TO VERY
WRONG CONCLUSIONS; RIGHT?
SO, YOU KNOW, THERE MAY BE
PEOPLE TALKING ABOUT GREED;
RIGHT?
REALITY IS IT IS DIFFICULT TO DO
DRUG DEVELOPMENT AND FAILURES
ARE COSTLY THAT IT CAN BASICALLY
TEACH ANY SMALL COMPANY AND THEY
HAVE USUALLY ONE OR A FEW DRUGS.
AND, YOU KNOW, FAILURE IS REALLY
INCREDIBLY COSTLY.
AND EVEN THOUGH THEY MAY HAVE
COLLECTED USEFUL DATA AND INVEST
LOTS OF MONEY INTO DEVELOPMENT
OF THE DRUG AND ONCE DRUG IS
ABANDONED THERE IS NOT REALLY
ANYBODY OR ANY ENTITY THAT OWNS
THE HISTORY OF THE DRUG OR OWNS
DATA; RIGHT?
THAT IS PHENOMENAL WASTE OF
PATIENT'S PARTICIPATION AND COST
AND EVERYTHING.
NON-PROFIT ENTITY THAT WOULD
CURATE DATA OR I DON'T KNOW
REGULATORY APPROVAL AND LAW IF
DRUG IS ABANDONED THAT IND
PACKET BECOMES AVAILABLE FOR --
AND CLEARLY I HEAR YOU.
I'M FOR WIN/WIN SOLUTIONS AND
BELIEVE THERE COULD BE SOLUTIONS
THAT ARE WIN/WIN FOR COMPANIES
INCENTIVIZING THE DRUG TO
DEPOSIT IT ACTUALLY. YOU EITHER
GET NOTHING OR SOMETHING BACK
POTENTIALLY IF THE DRUG WORKS.
>> I THINK SORRY GO AHEAD.
>> COMMON YOU MAY BE ON THE SAME
WAVELENGTH AND THINK THAT CARROT
APPROACH WILL WORKING BETTER
THAN A STICK AND AGREED WITH
COMMENT EARLIER ABOUT
INCENTIVIZATION AND WOULD WORK
BETTER THAN A SORT OF A YOU KNOW
A THREAT IF YOU WILL.
>> YES. SIMILARLY INCENTIVIZING
FOR RESCUER OF DRUG IN TERMS OF
IP AND IN UNITED STATES ALL
INCENTIVES GET PERVERSELY TURNED
AROUND AND IF YOU COULD
INCENTIVIZE PRESERVATION FOR IP
FOR THAT RESCUER ENTITY AGAIN.
AND FIGURING OUT HOW TO DO THAT
FROM A LEGAL POINT OF VIEW IS
EASIER SAID THAN DONE. YEAH.
>> YEAH. DR. BERTAGNOLLI, THE
NIH DIRECTOR HAD A PROVOCATIVE
SLIDE THAT SAID OUT OF 7,000
HUMAN DISEASES WE HAVE
TREATMENTS FOR FIVE% OF THEM.
IT WAS MIND BOGGLING TO ME.
YEAH. YOU KNOW, THERE IS --
THERE IS ENORMOUS COST TO THE
GOVERNMENT FOR HEALTHCARE OF THE
UNTREATABLE DISEASES.
IT TOOK NIH DIRECTOR TO
NEGOTIATE THESE THINGS; RIGHT?
WE ARE VERY CAPABLE PEOPLE AND
SURE I WOULDN'T BE ABLE TO
NEGOTIATE THAT; RIGHT?
IT TAKES THE -- IT TAKES THE
LEADERSHIP THAT BASICALLY
LEADERSHIP HAS TO BUY INTO THE
IDEA THAT THIS IS IMPORTANT FOR
SOCIETY AND HEALTHCARE AND
FINDING WIN/WIN SOLUTION THAT WE
ARE BOTH FOR GOVERNMENT AND
TAXPAYERS AND PHARMAINDUSTRY AND
ONE OTHER QUESTION WE WERE
DISCUSSING IS TO SKOOSH SECURE
IP RIGHTS; RIGHT?
THERE IS SO MUCH IN LITERATURE
AND THERE HAS BEEN DUE TOOMICS
TECHNOLOGIES AND DUE TO THESE
INSILICO STUDIES, THERE REALLY
IS ALMOST EVERY MONTH YOU FIND
INSILICO STUDY WITH BIOFORMATIC
APPROACH TO TRY TO FIND DRUGS
FOR NEW INDICATIONS AND THERE
ARE THESE HUNDREDS OF DRUG
DISEASE MATCHES.
OF COURSE, VAST MAJORITY OF THEM
WILL NEVER BE TESTED.
AND IT IS EVEN DIFFICULT TO
PRIORITIZE AMONG THESE.
THEY SHOULD BE TESTED AND
QUESTION IS ALSO IF THESE
STUDIES ARE NOW IN PUBLIC DOMAIN
WILL THEY INFRINGE IP RIGHTS?
WHAT IS THE PATENT PROCESS?
IF YOU HAVE OR DEVELOP NOW VERY
STRONG IN VIVO HUMAN DATA THAT
SUGGESTS THAT THERE IS A TARGET
LINKING THE DISEASE; RIGHT?
AND BASED ON THAT, YOU WANT TO
TROO ET THAT DISEASE, WILL THE
EXAMINER INVALIDATE THAT PATTERN
BECAUSE THERE IS COMPUTATIONAL
STUDY ALREADY THAT SUGGESTS
THERE MIGHT BE THIS TARGET
DISEASE RELATIONSHIP?
DO YOU HAVE ANY IDEA ON -- ABOUT
THAT?
>> I GUESS I WILL MAYBE TAKE A
STAB AT IT.
SO, FIRST OF ALL THE MOST DATA
YOU WILL HAVE IS GOING TO BE FOR
STUFF ALREADY ON THE MARKET.
YOU WON'T HAVE IT SO MUCH FOFR
PROPRIETARY DRUGS.
IT IS ALREADY AN AREA THAT WILL
BE VERY, VERY DIFFICULT FOR THE
REASONS THAT I DESCRIBED.
THE -- YOU KNOW, YOU POTENTIALLY
STILL HAVE THE -- EVEN IF YOU
WOULDN'T GET THE PATENT, I
SUPPOSE YOU MIGHT STILL HAVE
EXCLUSIVITY GRANTED FROM FDA.
IF THERE ARE GENERICS ON THE
MARKET, IT REALLY DOESN'T DO YOU
GOOD.
AND IT HAS BEEN PROPOSED AND
HEARD PEOPLE PROPOSE THE IDEA OF
WHAT IF YOUR PRESCRIPTION HAS TO
BE ACTUALLY TIED TO A SPECIFIC
LAB
LABEL?
DANGER THERE IS WE ARE DEPENDENT
ON ABILITY TO PRESCRIBE LABEL
AND PARTICULARLY FOR RARE
DISEASES AND TAKING AWAY THAT
ABILITY IT WOULD HAVE COMPLETELY
OPPOSITE EFFECT WHAT YOU ARE
INTENDING WHEN YOU SAY YOU WANT
TO TIE IT TO THE -- THE LABEL.
SO, YEAH.
>> ALL RIGHT LOOKS WE HAVE
MANAGED TO GET TO THE END OF THE
SESSION.
THANK YOU ALL.
WE WILL MONITOR IF WE HAVE
UNANSWERED QUESTIONS.
I WILL TRY TO SEND THEM YOUR
WAY.
THANK YOU FOR COMING AND
PARTICIPATING AND HOPE THAT IT
WAS USEFUL FOR OUR LISTENERS.
THANK YOU.
>> THANK YOU.
>> SO, ON BEHALF OF NIH AND
FIRST INDUSTRY DAY, I WOULD LIKE
TO WELCOME EVERYBODY TO THE
DIAGNOSTICS PANEL AND THERE IS
THOUGHT ABOUT NIH WE STUDY
SIMPLY THE BASIC BIOLOGY AND
CHEMISTRY OF LIFE.
WE ACTUALLY WORK WITH A NUMBER
OF TECHNOLOGIES IN ADDITION TO
BASIC BIOLOGY AND WILL STUDY
THERAPEUTICS AND VACCINES AND
DEVICES AND WEARABLES. EHEALTH
AND DIGITAL HEALTH AND HAVE A
CONCENTRATED FOCUS ON
DIAGNOS
DIAGNOSTICS.
WE HAVE ASSEMBLED A STRONG PANEL
FROM LATER COMPANIES TO PRESENT
EXCITING INNOVATIONS THAT ARE
GOING ON IN THE FIELD.
SO, FIRST, WE ARE GOING TO HAVE
A PRESENTATION BY THE VARIOUS
INVESTIGATORS AND COMPANY
EXECUTIVES.
PLEASE PUT QUESTIONS IN THE
CHAT.
WE WILL GET TO THEM AND WILL
START OFF WITH DR. DANIELLE
PELLA A SENIOR INVESTIGATOR IN
THE LABORATORY OF BIOORGANIC
CHEMISTRY IN THE NATIONAL
INSTITUTE OF DIE BEETIS AND
DIGESTIVE AND KIDNEY DISORDERS.
>> THANK YOU VERY MUCH.
I WILL SHARE MY SCREEN.
>> OKAY. HOPEFULLY YOU CAN SEE
MY SCREEN AND THANK YOU FOR THE
INTRODUCTION TO PRESENT TO YOU
TOD
TODAY.
I WILL TELL YOU I'M NOT A
PROFESSIONAL DIAGNOSTIC
DEVELOPER BUT REALLY MOSTLY AN
ORGANIC CHEMIST AND INTEREST IN
MOLECULE CALLED PEPTIDE NUCLEIC
ACID I WILL TELL YOU ABOUT TODAY
AND FUNDAMENTAL INTEREST IN THIS
LED DOWN THE ROAD TO AN INTEREST
IN TRANSLATION THAT IS
SPECIFICALLY FOR DOING HIV
DIAGNOSTICS LEADING TO CREATIVE
PARTNER CALLS ULTRA TECH AND
LOTS OF THE WORK IS FOCUSED BY
OFFICE OF AIDS INSTITUTE AND
RESEARCH AND STARTING OFF SAYING
A BIT ABOUT THE IMPORTANCE OF
DIAGNOSTICS IN THE REALM OF HIV
THAT IS ESSENTIAL TO FIGURE OUT
THE VIRUS AND WHO HAS IT OR
DOESN'T AND WILL HELP SPREAD THE
VIRUS IDEALLY AND PHYSICIANS
NEED THIS TO DECIDE WHAT
TREATMENT AND WHO WILL NEED
MEDICATIONS AND HIV TESTING
INVOLVES RAPID DETECTIONS THAT
IS USUALLY LOOKING FOR HIV VIRAL
ANTIGENS AND RAPID TESTS REQUIRE
FOLLOW UP TESTING AND HIV GOLD
STANDARD TO CONFIRM INFECTION IS
NUCLEIC ACID BASED TEST THAT
SIGNALS PRESENCE OF HRNA AND
AFTER HIV INFECTION IS CONFIRMED
DIAGNOSTICS ARE REQUIRED FOR THE
PATIENT FOR THE REST OF THE
PATIENT'S COURSE OF TREATMENT
AND REST OF THEIR LIFE AND
ROUTINE DIAGNOSTIC TESTING IS
ESSENTIAL IN WHAT IS HIV VIRAL
LOAD MONITORING THAT MEASURES
LEVELS OF HIV RNA IN INFECTED
INDIVIDUAL AND WHEN TO START
TREATMENT AND MAKE SURE THAT
MEDICATIONS ARE WORKING
CORRECTLY AND TARGET OF THE TEST
IS LOW AND IDEALLY VIRAL LOAD OF
100 COPIES OF M MILLIMETER OF
PLASMA OR LESS IS IDEAL AND
PHYSICIANS NEED TO KNOW IF
INCREASES IN VIRAL LOAD TO
INDICATE DEVELOPING RESISTANCE
TO CURRENT SIGNALING MEDICATIONS
NEED TO BE CHANGED TO SOMETHING
EL
ELSE.
THERE ARE MANY EXAMPLES OF USING
THIS TEST SUCCESSFULLY AND IN
WEALTHIER NATIONS SUCH AS OURS
AND DETECTION AND DIAGNOSIS AND
VIRAL MONITORING AND CHALLENGING
TO IMPLEMENT INTO RESOURCE
MONITORING SETTINGS AND NEED IS
GREAT
GREATEST.
MY RESOURCE GOAL WAS TO SEE IF
WE COULD TAKE AN APPROACH FOR
TESTING FOR HIVRNA AND MOVE IT
CLOSER TO PATIENT POINT OF CARE
AND CHALLENGE TO AVOID USING
TYPICAL AMPLIFICATION STRATEGIES
USING PRELIM RACES AND RESEARCH
IS GEARED FOR CHEMISTRY AND
UNDERSTANDING OF MOLECULES
CALLED PEPTIDE NUCLEIC ACIDS AND
MOLECULES COULD BE BENEFICIAL IN
THIS LANDSCAPE AND TELLING YOU
ABOUT PEPTIDE NUCLEIC ACID AND
BASIC STRUCTURE OF MOLECULE IS
SHOWN HERE AND IT FEATURES A
BACKBONE THAT IS NOT A NATURALLY
OCCURRING BACKBONE BUT ONE MADE
IN THE LAB ATTACHED IN BACKBONE
ARE NUCLEAR BASIS OF DNA AND
SYNTHETIC MOLECULES WE MAKE
USING CHEMICAL METHODS THAT
DON'T OCCUR IN NATURE AND
SEQUENCE OF NUCLEOTIDES WE CAN
MAKE LONGER IF NEEDED.
WHAT IS FASCINATING ABOUT
MOLECULES IS THEY BIND TO
SEQUENCES WELL AND MOLECULE
EXPOSED TO COMPLEMENTARY DNA
WILL BIND AND HAVE A NICE
MELTING TEMPERATURE TO BE
CHARACTERIZED.
PNA IS A FASCINATING MOLECULE.
IT OFTEN BINDS STRONGLY THAN
COMPLIMENTARY NUCLEOTIDES ITSELF
AND IS FASCINATING PNA DOESN'T
EXIST NATURALLY AND CAN'T BE
DEGRADED BY PRO TEASES OR
NUCLEASES AND DETECTION DEVICES
IS SHELF STABLE PART OF
MOTIVATION MOVING THIS FORWARD
AND SETTING IT UP DETECTING HIV
RNA AND DEVELOPING SYSTEM USING
ELIZA PROTOCOLS AND STARTING OFF
WITH A SEQUENCE OF HIV VIRUS AND
SEQUENCE IS SHOWN HERE 27 BASIS
AND MADE 2PNAS COMPLEMENTARY TO
ADJACENT REGIONS.
ONE IS COLOR CODED IN BLUE AND
IN GREEN AND ASSAY ATTACHING
GREEN PNA AND USING COVALENT
ATTACHMENT CHEMISTRY AND FREE
SOLUTION TO [INDISCERNIBLE] AND
HAS A BIOTIN GROUP AND IDEA HERE
PRESENCE OF HIV RNAPNAS WOULD
ADHERE TO PROSPECTIVE SEQUENCES
PERFORM ONES SURFACE AND HELD
TOGETHER WITH HYDROGEN BONDING
AND TAKE ADVANTAGE OF STANDARD
ELIZA REAGENTS AND IN PARTICULAR
THIS COMBINATION WITH CONJUGATES
WAS COMMERCIALLY AVAILABLE
BINDING TO BIOTIN ON THE SURFACE
AND SUBSTRATE FOR THE ENZYMES TO
DEVELOP A NEGATIVE COLOR IN
WELLS THAT YOU ARE SEEING HERE
INDICATING PRESENCE OF HIV AND
FOR NONPRESENCE OF HIV.
WE SET IT UP AND PNA WORKED AND
DETECTION LIMIT WAS NOT SO GOOD
AND GETTING LIMIT MUCH LOWER TO
BE CLOSE TO BEING CLINICALLY
RELEVANT AND HAD IDEAS TO DO
THIS AND RESEARCH FOR YEARS
LOOKED AT CHEMICAL BACKBONE
PROPERTIES OF NUCLEIC ACIDS AND
HAVE BEEN INTERESTED IN
INCORPORATING GROUPS LOOKING
LIKE THIS WITH SPECIFIC
STEREOCHEMISTRY WITH TWO AMEANS
COMING OFF THE RING AND FIND
THAT BINDING PROPERTIES WORK
BETTER AND THIS EXAMPLE HAS
THREE CYCLOPENTAINS IN THE
BACKBONE COMPARED TO ITS
PREDECESSOR THAT HAS NO
CYCLOPENTAINS THAT IS BETTER AND
SHOWING IT MUCH FURTHER AND THIS
EXAMPLE HAS CYCLOPENTAINS AT
EVERY POSITION AND IT IS
INCREASED 50 DEGREES COMPARED TO
THE ANALOG WITHOUT CRICOPEN TEEN
IN THE BACKBONE AND USING
STRATEGY EFFECTIVELY TO EFFECT
BINDING IN THE SYSTEM AND GOING
TO BASIC IDEA INCORPORATING
CYCLOPENTAINS IN HERE GOING FROM
0 TO 4 CAN INCREASE BINDING OF
GREEN PNA TO RESPECTIVE RNA
TARGET HELPING TO IMPROVE SIGNAL
BY HOLDING NUCLEIC ACID ON
SURFACE BETTER AND SOLUTION PNA
FIND ADDING BIOTINS TO THE END
IS HELPFUL FOR IMPROVING SIGNAL
AND MULTIVAILIENT FASHION IS
SHOWN HERE AND THOSE TOGETHER
HELP TO IMPROVE SIGNAL
SUBSTANTIALLY AND CARRY THIS
WITH OPTIMIZED SYSTEM ABLE TO
WORK WITH NIH TESTING HANDFUL OF
CLINICAL PATIENT SAMPLES WITH
VARIETY OF VIRAL LOADS
PHOTOGRAPH OF 96 WELL PLATE WITH
PATIENT SAMPLES SEEING NICE
RANGE WITH COLOR AND TESTING
SIMULTANEOUSLY WITH SYSTEM AND
[INDISCERNIBLE] SYSTEMS SHOWN
HERE AND QUANTIFYING VIRAL LOADS
AND CORRELATE THAT WITH
ABSORBANCE WE GET FROM OUR
METHOD AND IN HUNDREDS OF COPIES
THAT IS A CLINICALLY RELEVANT
RANGE AND NICE AND PUBLISHED AND
PATENTED AND THOUGHT IT WOULD BE
GOOD FOR TRANSLATION AND WANTED
TO WORK WITH COMBINASE TO
TRANSLATE THIS AND DIFFICULTY
CAME IN AND I'M A PRINCIPLE
INVESTIGATOR AND WORK IN A LAB
AND FAMILIAR WITH LABORATORY
TECHNIQUES AND CHEMISTRY AND
COMPOSITION WITH COMPANIES
BECAME CLEAR THAT FORMAT WASN'T
SUITABLE FOR ANYTHING THAT COULD
BE DEVELOPED WHERE WE WANTED TO
GO IN TRANSLATION SPHERE AND
ENZYMES WE ARE USING ARE NOT
DESIRABLE AND WEAK POINT IN
ASSAY AND THEY CAN HAVE SOME
CHALLENGES WITH WORKING.
THE OTHER THING THAT WAS A REAL
CHALLENGE TO ELIMINATE IS GET
RID OF PIPETTING AND PIPETTING
STEPS ARE LABORIOUS AND WORKING
TO ELIMINATE NEED FOR PIPETTING
AND SIGNAL SHOULD BE SOMETHING
TO BE CONVERTED TO A DIGITAL
READ OUT AND AFTER ALL THIS I
DESCENDED INTO TALKING WITH A
NUMBER OF COMPANIES AND TALKED
TO A LOT OF DIFFERENT PEOPLE AND
IDEAS AND ONE THAT HAS
TRANSLATED FORWARD IS ONE WITH
COMPANY CALLED ULTRA TECH AND
THEY ARE LOCATED IN IRELAND AND
I WILL SHOW GENERIC SLIDES WHERE
THEY ARE HEADED WITH THIS ASSAY
AND NOW.
WITH METHODS THEY WENT AND USED
RPNAS WITH CYCLO PENTAINS TO PUT
THEM ON DIFFERENT TYPES OF BEADS
TO ALLOW MOLECULES TO BE
EXTRACTED FROM BIOLOGICAL
SOLUTIONS.
THIS IS ALSO COMBINED WITH
DIFFERENT CODED MICROPARTICLES
AND ALLOW COMPLEXES WITH THE
ACTUAL ANOLITE TO BE TRANSPORTED
IN A DEVICE AND ULTRA TECH HAS A
LOT OF EXPERTISE IN MICROCHIP
ARENA THAT IS GOOD AT
MANUFACTURING MICROCHIPS WITH
SPECIFIC MICROCHIP WITH C MOSS
SILICON CHIP THEY ENGINEERED
THAT WILL BE ITEM THAT DETECTS
AND QUANTIFIES NUCLEIC ACID IN
ORIGINAL SAMPLE AND DETAILS
SYNTHETIC PNA PROBES THAT ARE
DESIGNED ARE REPRESENTED BY
KEYCHAIN PNA PROBES THAT ARE
SPECIAL PNAS ONE SIDE OF THEM
SHOWN IN BLUE HERE IS ABLE TO
RECOGNIZE TARGET RNA AND OTHER
PART HERE FREE IN THIS DEPICTION
IS ACTUALLY THE PART THAT BINDS
TO A CODED BEAD THAT THEN ALLOWS
THE SAMPLE TO BE TRANSPORTED AND
MIXED AROUND AND SEC SLIDE PNA
KEYCHAIN IS BOUND TO
COMPLEMENTARY STRAND ON THE BEAD
THAT IS TRANSPORTED TO SURFACE
OF CHIP THAT IS SPECIALLY
DESIGNED SO SIGNALS ARE DIRECTLY
READ THAT TRANSLATES TO INSTANT
ELECTRONIC SIGNAL AND EXAMPLE TO
REMOVE TYPICAL TYPES OF
BIOLOGICAL AMPLIFICATION AS MUCH
AS WE CAN AND FOCUS ON
ELECTRONIC AND COMPLETELY
SYNTHETIC SYSTEM FOR GENERATING
AN ACTUAL SIGNAL AND TARGETS FOR
THIS ARE HIV AND OTHER VIRAL
INFECTIN
-- WHAT A DEVICE WOULD LOOK LIKE
CALLED UBE HEALTH AND THERE IS
NO PRODUCT AVAILABLE CURRENTLY
AND GOAL IS TO HAVE SINGLE USE
PRODUCT TO GET SOMETHING TO BE
TESTED.
FEELING IS THIS IS ACHIEVABLE IN
THE NEAR FUTURE AND
ACKNOWLEDGING LAB AND SMALL LAB
MOSTLY POST DOCS AND POST
BACKAND WOULD LIKE TO SUPPORT
WHAT TRANSLATION I CAN AND ENJOY
WORKING WITH ULTRA TECH WITH
BRIAN AND TIM AND LEARNING AS
MUCH AS I CAN ABOUT ADVANCING
DIAGNOSTIC SYSTEMS AND
ACKNOWLEDGING INTRAMURAL PROGRAM
AND OFFICE OF AIDS RESEARCH TO
LET ME STEP OUT OF COMFORT ZONE
OF CHEMISTRY AND EXPLORE THIS
TRANSLATIONAL SPACE.
THANK YOU.
>> THANK YOU VERY MUCH.
REMINDER TO THE AUDIENCE TO MEEZ
CONVEY QUESTIONS THAT WE WOULD
BE HAPPY TO ASK.
I HAVE ONE QUICK QUESTION.
IT IS FOR DR. PELA WHILE WAITING
FOR OTHERS AND IF WE DON'T GET
MORE WE WILL MOVE ON AND HAVE
TIME, BY THE WAY, AT THE END OF
ALL OF THE PRESENTATIONS.
PLEASE GET YOUR QUESTIONS IN.
YOU ARE NOT OUT OF LUCK IF YOU
DON'T DO IT WHEN THE SPEAKER HAS
FINISHED.
IF YOU CAN COMMENT ON THE
SUCCESS STORY YOU SHOWED ABOUT
THE IMPORTANCE OF COMMERCIAL
DEVELOPMENT AND INPUT EXPERTISE
THAT WORKING WITH THE COMPANY
PARTNER BRINGS TO, YOU KNOW,
BENCH RESEARCHERS VERY
RESPECTFULLY SUCH AS YOURSELF.
>> SURE. I THINK THAT WORKING
IN A LAB WE HAVE OUR OWN VISIONS
HOW THINGS WORK ON THE BENCH.
WE ALL HAVE OUR SORT OF COMFORT
ZONE WITH DIFFERENT TECHNIQUES.
WHEN IT COMES TO ACTUALLY MOVING
A PRODUCT INTO THE REAL WORLD
SPACE, IT IS ANOTHER WORLD THAT
IS A COMPLETELY DIFFERENT WORLD
AND ONE I ABSORB SLOWLY THROUGH
TALKING WITH THE DIFFERENT
COMMERCIAL PARTNERS AS WELL.
I WILL ALSO SAY THAT ONE OF THE
INTERESTING THINGS IS TALKING
WITH A NUMBER OF DIFFERENT
COMPANIES AS I GO THROUGH THE
PROCESS AND THINK THAT EVERY
COMPANY HAS A VERY DIFFERENT
TYPE OF APPROACH.
IT BECAME CLEAR CERTAIN
APPROACHES WOULDN'T WORK WITH ME
AND WHERE I AM I GUESS.
I LIKE MORE RADICAL APPROACHES
WHICH IS WHERE ULTRA TECH IS
TAKING THINGS AND WE SEEM TO
WORK WELL TOGETHER.
I THINK THAT IT IS A HIGH RISK
PROJECT THAT THEY ARE TRYING TO
TAKE ON.
I AM HAPPY TO SUPPORT THEM.
THEY SEEM TO WORK WELL WITH ME.
HAVING COMMERCIAL INSIGHT I
THINK IS GREAT HONESTLY AND
FORCED ME TO THINK MORE
CAREFULLY ABOUT MY OWN RESEARCH
AND HOW NEW PROJECTS MAY NEED TO
SORT OF COME TOGETHER TO SORT OF
FURTHER THEM TO GO OUT OF MY LAB
AND BE USEFUL SOMEWHERE ELSE.
>> THANK YOU.
YOU KNOW, IT IS VERY MUCH A
BENEFICIAL SYMBIOTIC
RELATIONSHIP THAT WE PROVIDE A
LOT OF LEADER KNOWLEDGE AND WE
LEVERAGE COMPANY'S KNOWLEDGE IN
HOW TO GET TECHNOLOGIES
PROGRESSED TO PATIENTS THAT NEED
THEM.
THANKS VERY MUCH.
AGAIN, PLEASE PUT IN QUESTIONS
AS THEY COME UP.
WE WILL NOW SWITCH TO
[INDISCERNIBLE] WHO IS A
DIRECTOR OF CORPORATE BUSINESS
DEVELOPMENT TO TALK ABOUT
DIAGNOSTIC DEVELOPMENT
>> THANK YOU VERY MUCH, MICHAEL.
APPRECIATE THE OPPORTUNITY HERE
TO CHAT AND SPEAK WITH THE
AUDIENCE HERE AT NIH AND BOTH
PRESENT A LITTLE ON THE
CORPORATE SIDE.
SO A LITTLE BIT ABOUT MYSELF.
I HAVE A DOCTORATE IN
BIOCHEMISTRY AND MOLECULAR
BIOLOGY THAT GOES BACK QUITE A
FEW YEARS.
HAD THE OPPORTUNITY TO WORK AT
THE CUTTING EDGE OF PCR REALTIME
PCR AND WATCH FOR EVOLUTION IN
DNA SEQUENCING DURING THE COURSE
OF MY TIMES.
I DO KIND OF IDENTIFY AS AN
ESCAPED LAB RAT, AND HAVE LEFT
THE -- AFTER 20 YEARS OF
ACADEMIC RESEARCH MOVED INTO
PRODUCT DEVELOPMENT IN THE
PRIVATE SECTOR AROUND 2004, SO
ABOUT 20 YEARS AGO.
AND AFTER A STINT IN THE LAB
THERE, MOVED INTO TECHNOLOGY
DEVELOPMENT, WHICH INCLUDED
TECHNOLOGY SCOUTING AND
EVALUATIONS, AND ALSO BEEN
MANAGING LICENSING AND PATENT
FILINGS FOR INNOVATION PROGRAMS.
SO ULTIMATELY THE COMPANY I WAS
WITH WAS ACQUIRED BY QIAGEN, I'M
NOW CURRENTLY DIRECTOR OF GLOBAL
LICENSING WITHIN THE IP AND
LICENSING TEAM IN CORPORATE
BUSINESS DEVELOPMENT.
WHILE THE COMPANY IS GERMAN, I'M
BASED HERE IN MARYLAND, WHICH IS
WHERE AMERICA'S HEADQUARTERS ARE
LOCATED SO WE'RE RIGHT IN THE
MIDST OF THE AREA FOR
INTERACTING WITH A LOT OF THE
NIH AND OTHER FINE INSTITUTIONS
THAT ARE HERE IN THE
WASHINGTON, D.C. AREA.
BUT WE ARE TRULY A GLOBAL
COMPANY IN APPROACH.
IN WAY OF THE SLIDE THAT I HAVE
HERE, MANY RECOGNIZE THE BRA
BRANDING, SO THIS IS SOMETHING
WE'LL COME BACK TO THE A OTHER
TIMES.
WE'VE BEEN AROUND SINCE ABOUT
1984.
THIS IS -- I NEED TO PUT OUR
DISCLAIMERS IN ABOUT FORWARD
LOOKING AND HISTORICAL
STATEMENTS ON HERE.
BUT REALLY WHERE WE'RE COMING
THROUGH IS WE ARE A FACILITATOR
IN MANY WAYS.
WE ARE A TECHNOLOGY-BASED
COMPANY THAT FOCUSES PRIMARILY
AROUND NUCLEIC ACID TESTING AND
ANALYSIS, AND ALL OF ITS VARIOUS
SPECTRUMS, WITH THE GOAL OF
MAKING IMPROVEMENTS IN LIFE
POSSIBLE.
REALIZING THAT THIS IS NOT
SOMETHING WE CAN DO ON OUR OWN,
BUT RATHER SOMETHING THAT WE DO
WITH A VARIETY OF DIFFERENT
PARTNERS ACROSS THE SPECTRUM.
AND I'LL ELABORATE MORE ON
THOSE.
WHEN YOU LOOK AT OUR BUSINESS AS
A WHOLE AND OUR INTERESTS, WE
ARE LOOKING AT A PHRASE THAT WE
CALL SAMPLE TO INCITE.
AS THE GENETIC AND GENOMICS
REVOLUTION HAS EVOLVED, THE
TECHNICAL DETAILS AND
COMPLEXITIES OF THE TESTS THAT
ARE BEING RUN ON PEOPLE'S
SAMPLES FOR DNA AND RNA AND
EPIGENETICS HAVE BECOME
INCREASINGLY COMPLEX AND HIGHLY
SPECIALIZED TO THE EXTENT THAT
MANY OF THE PRACTITIONERS OR
PEOPLE ASKING QUESTIONS AT THE
FRONT END ARE NOT SKILLED IN THE
DETAILS OF THE WAYS OF GETTING
THE ANSWER, BUT NEED THOSE
ANSWERS IN ORDER TO PROVIDE THE
GUIDANCE TO PATIENTS AND/OR
OTHER SORTS OF PEOPLE ASKING
QUESTIONS OF NUCLEIC ACIDS.
SO THIS HAS BEEN A CORNERSTONE
FOR US.
WE ARE A SOLID MID CAP COMPANY,
WE'RE PUBLICLY HELD ON THE
NEW YORK STOCK EXCHANGE.
THESE NUMBERS ARE HERE FROM OUR
2022 PERFORMANCE, AGGREGATING
OUR 2023 PERFORMANCE STILL.
THIS IS ABOUT $2 BILLION WHEN WE
ARE TRULY A GLOBAL COMPANY
COVERING THE AMERICAS, EUROPEAN,
MIDDLE EAST AFRICA AS WELL AS
THE ASIAN PACIFIC MARKETS.
FUNDAMENTALLY, WE ARE INTERESTED
IN SELLING CONSUMABLES AND KITS.
THESE ARE THE NUCLEIC ISOLATION
KITS, THEY ARE PCR ASSAYS.
INSTRUMENTS ARE A MEANS OF
MAKING IT EASIER FOR CUSTOMERS
TO USE OUR KITS, AND EASIER AND
LESS TIME-INTENSIVE TO ARRIVING
AT THE RESULTS THAT THEY NEED
FROM THE SAMPLES THAT THEY HAVE.
WE COVER A RATHER BROAD SPECTRUM
WHEN I SAY THE CUSTOMERS, WHICH
INCLUDES ABOUT A 50/50 SPLIT
BETWEEN CLINICAL AND MOLECULAR
DIAGNOSTIC CUSTOMER BASE, AND
THE LIFE SCIENCES OR BASIC
RESEARCH BASE.
A COMPANY IS MORE THAN 6,000 --
AT THIS TIME WITH OVER HALF A
MILLION CUSTOMERS WORLDWIDE THAT
RELY ON OUR PRODUCTS.
AND WHEN YOU LOOK AT THE
PRODUCTS AND WHO IS USING IT,
ONE OF THE THINGS THAT WE HAVE A
REALLY NEAT TIME WHEN IT COMES
TIME FOR NOBEL PRIZES IS SEEING
HOW MANY OF THE WINNERS THAT
YEAR IN CHEMISTRY AND MEDICINE
END UP HAVING THEIR LAB PHOTOS
WITH A QIAGEN BOX IN THE
BACKGROUND.
WE'RE PRETTY CONFIDENT THIS IS
NOT AN INTENTIONAL THING ON
THEIR PART, WE CERTAINLY AREN'T
LOBBYING FOR THEM TO DO THAT,
BUT I THINK IT REALLY KIND OF
HIGHLIGHTS JUST HOW UBIQUITOUS
WE ARE IN THE SPACE OF DNA AND
NUCLEIC AND RNA ANALYSIS.
THAT'S THE STARTING POINT FOR
EXTRACTING.
WHEN YOU LOOK AT OUR BUSINESS
FOCUSES, THIS SLIDE REALLY, I
THINK, ENCAPSULATES THE FOUR
MAJOR FOCUS AREAS FOR OUR
COMPANY.
THAT IS REALLY THE KNOWLEDGE
ABOUT DNA/RNA PROTEINS, WHILE WE
FOCUS PRIMARILY ON DNA/RNA,
PRIMARILY THESE ARE THE
PRECURSORS GOING INTO PROTEINS
DOING THE WORK FOR THE COMPANY,
AND WE RECOGNIZE THAT THERE IS
ALWAYS GOING TO BE A NEED FOR
THIS TO BE ONE PIECE OF THE
OVERALL PUZZLE THAT IS ANYTHING
IN BIOLOGY.
WHEN YOU LOOK AT SPECIFIC AREAS
IN WHICH WE'VE TARGETED,
TUBERCULOSIS IS ONE AREA WHERE
WE HAVE A MAJOR IMPACT ON THE
MARKET THROUGH OUR TB TEST
FRANCHISE, WHICH IS ACTUALLY
BASED HERE IN MARYLAND FOR
MANUFACTURING AND PRODUCT
DEVELOPMENT.
THIS IS A GLOBAL ISSUE, BUT IT
AFFECTS THE FIRST WORLD AS MUCH
AS -- AS WELL AS
RESOURCE-CHALLENGED AREAS AND
WE'VE APPROACHED THIS FROM
MULTIPLE WAYS.
CANCER REMAINS A LEADING
INTEREST FOR US.
WE HAVE DIAGNOSTICS FRANCHISE
THAT IS FOCUSED ON VARIOUS TYPES
OF CANCER DIAGNOSTICS.
AND ALSO THIS IS AN AREA WHERE
WITH THE AMOUNT OF RESEARCH THAT
GOES ON IN TERMS OF REALLY
TRYING TO UNDERSTAND THE
COMPLEXITIES AND THE TIES TO
GENETIC CHANGES THAT ARE
HAPPENING THROUGH SOMATIC
MUTATIONS AND RECOMBINATIONS IN
CANCER, WHERE IT ALSO OVERLAPSE
WITH OUR RESEARCH PRODUCTS AND
TOOLS.
FINALLY AS A FOCUS AREA,
INFECTIOUS DISEASE, WHICH HAS
REALLY COME ABOUT, A LOT OF
PEOPLE HAVE REALLY KIND OF
GAINED A DIFFERENT APPRECIATION
IN LIGHT OF THE PAN DEME PANDEMS
AFTERMATH AS TO HOW MUCH IMPACT
A VIRAL PATHOGEN CAN HAVE ON NOT
JUST INDIVIDUALS BUT GLOBAL
ECONOMIES ALL AT THE SAME TIME.
SO THIS SLIDE KIND OF GOES A
LITTLE MORE DEEPER INTO HOW WE
VIEW A SAMPLE INSIGHT AND THE
COMPLEXITIES ALONG THIS.
YOU'LL SEE SORT OF THREE COLUMNS
HERE STARTING WITH THE VARIOUS
TYPES OF SAMPLES THAT WE CAN
PROCESS, AND EACH OF THOSE
SAMPLES REQUIRES A DIFFERENT SET
OF CIRCUMSTANCES, REAGENTS, FOR
THE EFFECTIVE AND EFFICIENT
EXTRACTION OF THE TARGETED
MATERIAL.
TARGETED NANOLYTES, CIRCULATING
FREE DNA, SMALL INDIVIDUAL AND
ENVIRONMENTAL DNAs THAT COULD
BE RNAs AND SO DEPENDING UPON
THE NATURE OF THE QUESTION, MUCH
OF THIS WORKFLOW IS DICTATED BY
THE SAMPLE, THE TYPE OF
QUESTION, AND WHAT IS THE
ANALYTICAL APPLICATION THAT'S
BEING USED ON THIS.
YOU CAN VIEW IT AS SORT OF A
COMBINATIONAL MATRIX ALONG HERE.
MUCH OF WHAT WE DO WHEN WORKING
WITH CUSTOMERS IS HELP THEM
IDENTIFY WITH THEIR PARTICULAR
STARTING SAMPLE, THEIR
PARTICULAR QUESTION AT THE END,
WHAT ARE THE MOST EFFECTIVE WAYS
TO GET THE ANSWER OUT OF THAT
SAMPLE AND FOR THEM TO USE THAT
SAMPLE TO EITHER ADVANCE THEIR
RESEARCH OR HELP TREAT PATIENTS.
ANOTHER WAY OF LOOKING AT OUR
FOCUS AREA KIND OF BREAKS DOWN
INTO THE ACTUAL BUSINESS UNITS,
AND WE'VE HAD SOME CHANGES
OURSELF IN TERMS OF RESPONDING
TO THE PANDEMIC AND RESPONDING
TO GLOBAL CHANGES, RESPONDING
SOME OF OUR OWN EFFORTS AS WELL
GOING BACK INTO 2019.
WHAT YOU'LL SEE ACROSS THE TOP
ROW HERE IS REALLY WHAT WE CALL
OUR FIVE PILLARS OF GROWTH.
FOCUSING ON THE FIRST TWO, WHERE
THESE ARE AREAS THAT WERE WELL
ESTABLISHED AND HAVE BEEN AROUND
IN QIAGEN IN THE FIRST CASE
SINCE OUR FOUNDING IN 1984, ON
SAMPLE ISOLATION TECHNOLOGY TO
ONE OF OUR MAJOR INVESTMENTS
INTO DIAGNOSTICS OR QUANTIFERON
AROUND 2010.
AND THIS PARTICULAR ONE, THE
QUANTIFERON TUBERCULOSIS TEST IS
AN IMMUNE RESPONSE TEST AND IT
IS NOT A NUCLEIC ACID TEST, BUT
RATHER A TEST ON A PLATFORM
CALLED INTERFERON GAMMA
RELEASING ASSAY, WHICH INSTEAD
OF ACTUALLY TRYING TO IDENTIFY
AND ACTUALLY TAG THE PATHOGEN
ITSELF AND PULL IT OUT, IS
ACTUALLY A WAY OF LOOKING AT THE
PATIENT'S IMMUNE RESPONSE AND
WHETHER THEY HAVE AN IMMUNE
MEMORY FOR THE PA PATHOGEN IN
QUESTION FOR THIS.
THREE OTHER AREAS WE'VE BEEN
PRETTY EXCITED ABOUT BRINGING
INTO PLAY ARE ACTUALLY THREE OF
OUR INSTRUMENT SYSTEMS THAT WERE
LAUNCHED EITHER SHORTLY BEFORE,
WITHIN ABOUT A YEAR BEFORE THE
PANDEMIC STARTED IN THE CASE OF
THE QIASTAT VX OR THE FIRST YEAR
OF THE PANDEMIC IN THE CASE OF
THE HIGH-THROUGHPUT TESTING
SYSTEM FOR THE CLINICAL LABS AND
THE DIGITAL PCR PLATFORM FOR THE
RESEARCH AREA TO HELP PROVIDE A
DIFFERENT WAY AND ENHANCEMENTS
IN TERMS OF SENSITIVITY AND
LOWER LIMITS OF DETECTION OF PCR
IN THE RESEARCH SETTINGS.
BELOW THAT YOU'LL SEE WE ALSO
HAVE OTHER AREAS OF FOCUS.
WE ARE VERY STRONG AND ACTIVE IN
THE GENOMICS FIELD.
THIS IS FROM BOTH THE SAMPLE
PREP AND LIBRARY PREPARATION,
ESPECIALLY AROUND TARGETED DNA
SEQUENCING.
WE HAVE A WHOLE BUSINESS
DIVISION IN HUMAN IDENTIFICATION
AND FORENSICS THAT SPANS THE
ENTIRE WORKFLOW AS WELL.
THIS IS NOT A MARKET THAT PEOPLE
TYPICALLY IN OUR CLINICAL AND
BASIC RESEARCH SETTINGS HEAR
ABOUT, BUT THIS IS A VERY
IMPORTANT MARKET SEGMENT WHEN
YOU LOOK AT NOT ONLY THE COURT
CASES THAT ARE UTILIZING
EVIDENCE THAT IS COMING IN HERE,
BUT ALSO TO SUPPORT MASS
CASUALTY INCIDENCES AND BODY
IDENTIFICATIONS FROM THOSE, WHAT
WHETHER THEY BE NATURAL
DISASTERS OR WARTIME DISASTERS
WHERE THERE ARE HUMAN REMAINS
THAT NEED TO BE REPATRIATED AND
IDENTIFIED SO THAT FAMILIES CAN
HAVE CLOSURES ON THEIR LOVED
ONES.
ONCOLOGY IS ALSO TIED INTO SOME
OF THESE TESTING PLATFORMS,
ESPECIALLY THE PCR TYPES OF
SYSTEMS WE HAVE AND THE NEXT
GENERATION DNA SEQUENCING, AND
OF COURSE WITH SEQUENCING AND
SOME OF THE MASSIVELY PARALLEL
THINGS COMING OUT INITIALLY WITH
MICROWAVES, THE ABILITY TO
MANAGE THE EXTREMELY LARGE LOAD
OF NUCLEIC ACID SEQUENCE DATA
THAT IS COMING OUT WITH THE
GENOMICS REVOLUTION IS A MAJOR
COMPONENT AND ESSENTIAL TO
UNDERSTANDING WHAT IS HAPPENING
FROM THE SAMPLE AND THE AMOUNT
OF DATA THAT'S COMING OUT.
QIAGEN IS THE WORLD'S LEADER IN
BIOINFORMATICS ANALYSIS AND
INTERPRETATION COMING OFF OF
NUCLEIC ACID SEQUENCING AND ALSO
OTHER TYPES OF NUCLEIC ACID
TESTING.
OUR BUSINESS DIVISION HERE IS
SPLIT OUT GLOBALLY BETWEEN THE
UNITED STATES AND EUROPE, BUT WE
HAVE -- AND IT ALSO COVERS
RESEARCH APPLICATIONS AS WELL AS
CLINICAL INSIGHTS APPLICATIONS.
THE FINAL POINT I LIKE TO ALSO
BRING OUT TO PEOPLE THAT IS
REALLY AGAIN NOT INSIDE THE
COMMON KNOWLEDGE OF QIAGEN BUT
AS AN OEM PROVIDER.
BECAUSE WE DO RECOGNIZE THAT HE
WITH CANNOT MEET AND ADDRESS
EVERY INVESTIGATOR'S NEED BUT WE
HAVE TECHNICAL REAGENT AND
INSTRUMENT CAPABILITIES THAT CAN
BE UTILIZED BY OTHER COMPANIES.
WE HAVE A VERY STRONG OEM
BUSINESS THAT SPANS A RANGE FROM
ENZYMES, SIMPLY ISOLATED
ENZYMES, WHICH SUPPORT MANY OF
THE NGS SEQUENCING KITS THAT ARE
ON THE MARKET TO WHOLE KITS THAT
ARE LABELED FOR OUR PARTNERS, TO
INSTRUMENT SYSTEMS THAT OUR
PARTNERS HAVE THAT UTILIZE --
THAT CARRY 5 10K CLEARS WITH
THEIR ASSAYS FOR FDA APPROVAL
BUT PLATFORMS YOU WILL NOT
REGULARLY SEE IN THE QIAGEN
CATALOG.
SO THIS BUSINESS TO BUSINESS
OFFERING HAS ALSO BEEN A VERY
IMPORTANT PART IN THE WAY THAT
WE WORK.
I KIND OF LIKE TO WRAP THAT
AROUND THE FACT THAT IT
HOPEFULLY IS STARTING TO COME
ACROSS THAT QIAGEN IS A VERY
COLLEGIAL COMPANY TO WORK WITH.
WE'RE VERY FLEXIBLE WHEN IT
COMES TO PARTNERING AND REALLY
ARE LOOKING FOR WAYS THAT WE CAN
OPTIMIZE THE VALUE FOR BOTH THE
COMPANY AS WELL AS THE PARTNERS
THAT WE'RE WORKING WITH.
I'D LIKE TO SORT OF WRAPPING UP
ON MY SIDE OF TWO OTHER POINTS
OF QIAGEN AS A COMPANY, I
MENTIONED IT EARLIER BUT WE
TRULY ARE A GLOBAL COMPANY.
WHEN YOU LOOK AT THE DIAGNOSTICS
MARKET ESPECIALLY, THIS MARKET
GLOBALLY IS VERY MUCH SEGMENTED
INTO WHICH MARKET REGION YOU'RE
GOING TO.
BOTH FROM THE SIZE AND
ECONOMIC -- IN TERMS OF ECONOMIC
OPPORTUNITY FOR THAT MARKET, AS
WELL AS REGULATORY OVERSIGHT FOR
GETTING APPROVALS AND USING IN
THOSE MARKETS.
I'VE MENTIONED THE QUANTIFERON
TB ASSAY WHICH IS FULLY
U.S.-APPROVED IBB ASSAY
AVAILABLE IN THE UNITED STATES
AND OTHER COUNTRIES AROUND
EUROPE, BUT IT IS ONE THAT
REQUIRES A LEVEL OF COMPLEXITY
THAT IS NOT READILY AVAILABLE IN
EMERGING COMPANIES IN LOWER
RESOURCE PARTS OF THE WORLD.
WE HAVE CREATED A VERSION OF
THIS THAT IS BASED ON MORE OF A
LATERAL FLOW READOUT CALLED THE
QIA REACH PROGRAM MUCH MORE
STANDALONE, DOES NOT REQUIRE THE
HIGH COMPLEXITY LABORATORY
SETTINGS TO HELP RUN THAT TO
BRING TB TESTING INTO MORE OF A
LARGER POPULATION SCREENING
WORLD.
SIMILARLY, WITH OUR HPV ASSAYS,
ONE OF OUR FIRST REAL AREAS INTO
DIAGNOSTICS, WE HAVE A CARE HPV
TETEST THAT TAKES US DOWN TO SEF
SAMPLING INSTEAD OF HAVING TO GO
TO A GYNECOLOGIST TO OBTAIN THE
SAMPLE OR PAP SMEARS.
SO THESE ARE AREAS THAT WE'VE
COME THROUGH.
IN LIGHT OF THE PANDEMIC ALSO,
THE AWARENESS OF INFECTIOUS
DISEASE IDENTIFICATION FOR
PUBLIC HEALTH, MONITORING AND
IDENTIFICATION AND HELPING TO
BOTH SUPPORT AND START
RESPONDING FOR PANDEMICS IN A
FASTER, MORE EFFICIENT MANNER.
HAS INVOLVED US IN MANY MORE
PUBLIC HEALTH LABORATORIES,
MILITARY ORGANIZATIONS WHERE THE
PUBLIC HEALTH OF WAR FIGHTERS IS
IMPORTANT, AS WELL AS EMERGING
COUNTRIES THAT DO NOT
HAVE THE ACCESS TO SORT OF THE
MODERN MEDICAL LABORATORY
SYSTEMS THAT HELP REALLY --
ENABLE THE WORLD TO RESPOND MORE
QUICKLY AND EFFECTIVELY AGAINST
EMERGING PATHOGENS.
WE ARE HEARING FROM GLOBAL
CLIMATE CHANGE EXPERTS AND
ENVIRONMENTAL AND ECOLOGISTS
THAT THIS IS CHANGING THE NATURE
OF ZOONOTIC INFECTIONS, WHERE
WE'RE LIKELY TO SEE MORE
TRANSFER OF ANIMAL PATHOGENS
INTERACTING WITH HUMANS, AND
THAT CLIMATE CHANGE IS ONE OF
THE THINGS THAT'S LEADING SOME
OF THESE CONTACTS BETWEEN THESE
THINGS SO THIS IS A WAY THAT WE
CAN HELP ADDRESS THAT.
FINALLY COMING BACK TO THE FACT
THAT, AS I MENTIONED, THE GLOBE
IS CHANGING, AND IT'S CHANGING
IN A VARIETY OF DIFFERENT WAYS
THAT WE HAVEN'T -- OVER THE LAST
10 YEARS THAT WE HAVE NOT SEEN
IN DECADES THAT FORMED THE END
OF OUR 20TH CENTURY.
TO HELP ADDRESS THIS, QIAGEN IS
VERY MUCH AWARE OF THE NEED TO
REDUCE OUR CARBON FOOTPRINT.
FOR BETTER OR FOR WORSE, THE
MEDICAL INDUSTRY, DIAGNOSTICS,
HAS BECOME ONE OF A -- REALLY
FOCUSED ON SINGLE USE PLASTICS.
AND PLASTIC AS A VERSATILE
MATERIAL HAS BEEN A REALLY
IMPORTANT PART, IF YOU LOOK AT
QIAGEN KITS, THE FIRST AMOUNT OF
WEIGHT IS ACTUALLY IN THE LIQUID
REAGENT BUFFERS, BUT THE NEXT
MASS OF THE KITS ARE TYPICALLY
IN PLASTICS.
THAT GOES NOT ONLY FOR THE
ACTUAL TUBES AND COLUMNS IN
THERE BUT ALSO HOW IT HAS BEEN
PACKAGED FROM THINGS LIKE ZIPLOC
BAGS TO BLISTER PACKS.
THESE ARE ALL EFFORTS THAT WE
ARE LOOKING AT AND EVALUATING
WAYS THAT WE CAN REDUCE OUR
CARBON FOOT PRINT, INCREASE
RECYCLABLITY TO OTHER MODES WE
CAN GO IN AND TO OVERALL REALLY
BE GOOD GLOBAL CITIZENS WHEN IT
COMES TO ENVIRONMENTAL
PRACTICES.
ON THE FRONT OF SOCIAL ON THERE,
WE ARE A GLOBAL COMPANY.
ONE OF THE THINGS I REALLY ENJOY
ABOUT BEING IN A GLOBAL COMPANY
IS THE EXPOSURE TO A VARIETY OF
CULTURES, AND THIS GOES BACK TO
MANY YEARS AND DECADES AS QIAGEN
HAS BEEN GLOBAL.
UNFORTUNATE THAT WE DO HAVE A
STRONG -- WE HAVE A STRONG
CULTURE THAT FOSTERS DIVERSE AND
AND INCLUSION AND THIS IS
SOMETHING THAT GOES ACROSS ALL
OF OUR ASPECTS OF BUSINESS.
WE'RE HAPPY TO SAY THAT WHEN WE
LOOK AT OUR WOMEN IN LEADERSHIP,
WE ARE MAKING IMPROVEMENTS IN
BRINGING THAT UP.
IF WERE TO LOOK AT GENDER
DISTRIBUTION ACROSS THE ENTIRE
COMPANY WE'RE RIGHT ABOUT AT 50%
FEMALE, 50% MALE ACCORDING TO
THE BINARY BUT ALSO VERY MUCH
INCLUSION AND ACTIVE COMMUNITY
OF PEOPLE THAT DO NOT FALL
WITHIN THE BINARY RANGE OF MALE
OR FEMALE ON THEM.
AS SCIENTISTS, WE RECOGNIZE THAT
THIS IS A SPECTRUM AND THAT THIS
IS IMPORTANT TO THESE PEOPLE TO
BRING THEIR THOUGHTS IN ORDER TO
MAINTAIN THE INNOVATIONS THAT WE
HAVE AND INJI NEWT THAT KEEPS US
AT THE FOREFRONT OF OUR
INDUSTRY.
FINALLY IN TERMS OF GOVERNANCE
ENSURING RESPONSIBILITY OF
CORPORATE PRACTICE, WE EXTEND
THAT OUT TO OUR SUPPLY CHAIN AS
WELL AS OUR EMPLOYEES AND HOW WE
HELP WORK WITH THOSE.
SUPPLY CHAIN HAS BEEN
PARTICULARLY IMPORTANT AS WE'VE
SEEN OVER THE LAST FIVE YEARS
NOW AND HOW THE PANDEMIC HAS
PROVIDED DISRUPTION ON GLOBAL
SUPPLY CHAIN, WE'VE SEEN HOW
WARS AND WARFARE ARE IMPACTING
SUPPLY CHAIN.
MOST RECENTLY WITH NOW THE
HOOTIE AND YEMEN APLAQUING
SUPPLY CHAIN GOING THROUGH THE
SUEZ AND RED SEA.
WE'VE ALSO SEE THAT IN SUPPLY
CHAIN AND CLIMATE IMPACTS WHERE
THE PANAMA CANAL IS HAVING TO
REDUCE THE NUMBER OF SHIPS THAT
CAN TRANSIT THE CANAL BECAUSE
THE DROUGHT IS LOWERING THE
LEVELS OF THE LAKES AND REDUCING
THE NUMBER --
>> WE'RE GOING TO NEED TO ASK
YOU TO WRAP UP.
>> SO OVERALL, QIAGEN IS REALLY
WELL ABLE TO SUPPORT OUR
CUSTOMERS AS WE MOVE FORWARD,
AND I THANK YOU AGAIN FOR YOUR
TIME AND WELCOME THE OPPORTUNITY
TO ANSWER ANY QUESTIONS THAT YOU
HAVE DURING OUR DISCUSSION
SECTION.
>> I DO HAVE A QUESTION FOR THE
DIAGNOSTIC COMPANIES THAT WE
HAVE, BUT I'M GOING TO HOLD IT
UNTIL LAST TO SEE HOW MUCH TIME
WE HAVE LEFT.
SO FOR THE MOMENT, I'M GOING TO
GO ON TO JONATHAN COHEN, FOUNDER
AND CEO OF 2020 GENE SYSTEMS.
>> THANK YOU VERY MUCH, MICHAEL.
VERY NICE TO -- I APPRECIATE THE
OPPORTUNITY TO BE WITH YOU THIS
AFTERNOON.
I'M GOING TO SHARE A COUPLE OF
SLIDES.
I ASSUME THOSE ARE VISIBLE AT
THIS POINT?
>> YES.
>> SO WE ARE LOCATED JUST
OUTSIDE OF OUR NATION'S CAPITOL
IN GAIT BU GAITHERSBURG, MARYLA.
>> WE'RE SEEING YOUR DECK BUT
IT'S NOT IN PRESENTATION MODE.
>> THANK YOU FOR THAT.
IS THAT BETTER?
>> THAT IS GREAT.
THANK YOU.
>> THANK YOU FOR THAT.
I WANT TO TOUCH ON A LITTLE BIT
ABOUT OUR COMPANY AND OUR
RELATIONSHIP WITH THE NIH, WHICH
IS LOCATED ONLY A COUPLE MILES
FROM US, BECAUSE WE'VE HAD A
VARIED ARRAY OF INTERACTIONS
OVER THE YEARS.
FIRST OF ALL, WE ARE A CLINICAL
LAB COMPANY, SO WHILE REALLY
THERE'S TWO TYPES OF DIAGNOSTICS
COMPANIES, THERE ARE COMPANIES
LIKE QIAGEN THAT YOU JUST HEARD
FROM THAT MAKE AND SELL KITS,
BUT USUALLY VERY OFTEN, THOSE
KITS ARE USED BY HIGH
COMPLEXITY -- WHICH WERE
REFERRED TO AND WE ARE ONE SUCH
LAB.
SO WE DEVELOP AND COMMERCIALIZE
WHAT ARE CALLED LAB-DEVELOPED
TESTS.
AND WE HAVE LICENSURE FROM BOTH
CLIE YA, WCLIA, COLLEGE OF AMERN
PATHOLOGISTS, WE HAVE
HISTORICALLY HAD A FOCUS ON
EARLY CANCER DETECTION AND THAT
REMAINS SO.
WE LIKE MANY LABS PIVOTED DURING
THE PANDEMIC AND WERE A BIG
PROVIDER OF COVID PCR TESTS HERE
IN MARYLAND AND IN THIS REGION.
WE BECAME ACTUALLY THIS YEAR, WE
WERE RANKED NUMBER ONE FASTEST
GROWING COMPANY IN THE STATE OF
MARYLAND BY REVENUE, LARGELY
BECAUSE OF OUR COVID TESTING
LAST YEAR.
BUT OUR MAIN FOCUS NOW IS
SOMETHING CALLED AN MSAD.
HERE IN WASHINGTON WHEN SOMEBODY
BECOMES IMPORTANT, IT GETS AN
ACRONYM.
THIS ACRONYM STANDS FOR
MULTI-CANCER EARLY DETECTION.
THIS WAS AN APPROACH PIONEERED
BY A COMPANY THAT HAS AN MCED ON
THE MARKET, OURS IS VERY
DIFFERENT BUT PRIMARILY BASED ON
PROTEINS, NOT CIRCULATING TUMOR
DNA.
I'M ALSO GOING TO MENTION ABOUT
AN ENTITY THAT WE HAVE THAT I
BELIEVE IS UNIQUE AND COULD BE
OF INTEREST TO SOME IN THE
AUDIENCE THIS AFTERNOON.
WE HAVE CREATED WHAT WE THINK IS
THE FIRST ACCELERATOR FACILITY
FOR COMPANIES THAT ARE DEVEL
DEVELOPING OR HAVE DEVELOPED
LAB-DEVELOPED TESTS OR LDTs
THAT WANT TO LAUNCH IN THE
UNITED STATES MARKET WITHOUT THE
COST AND BURDEN OF EITHER
GETTING AN FDA APPROVAL FOR A
KIT, AN IVD KIT, OR BUILDING OUT
THEIR OWN LAB AND STAFFING IT
AND EQUIPPING IT.
SO I JUST HAVE A FEW SLIDES TO
SHARE WITH YOU.
I KNOW THAT WE'RE SHORT ON TIME.
THE MCED, SINCE THIS IS AN NIH
SYMPOSIUM, I WOULD LIKE TO SPEND
A LITTLE TIME ON THE
GOVERNMENT'S INTEREST IN
MCEDs, AND AS WE OFTEN SAY
HERE IN WASHINGTON, BOTH SIDES
OF PENNSYLVANIA AVENUE HAVE
EXPRESSED INTEREST -- OR NOT
JUST EXPRESSED INTEREST, HAVE
TAKEN ACTION TO ADVANCE THIS
FIELD.
CONGRESS HAS A BILL THAT HAS
REMARKABLE BIPARTISAN SUPPORT,
WELL OVER 200 MEMBERS, SENATE
AND HOUSE, REPUBLICAN AND
DEMOCRAT, TO CREATE A PATHWAY
FOR CMS TO COVER THESE TESTS,
AND TO STORE S SHORTEN THE TIMEE
ASSOCIATED WITH THAT.
THEY HAVE INCLUDED PRESIDENT
BIDEN'S CANCER MOONSHOT PROGRAM
AS A PRIORITY AND FUNDING FROM
THAT PROGRAM HAS FLOWED TO THE
U.S. NCI NATIONAL CANCER
INSTITUTE, MICHAEL'S
ORGANIZATION, TO BASICALLY
SUPPORT RANDOMIZED CLINICAL
TRIALS.
PROGRAM KNOWN AS VANGUARD AND
THEY'RE GOING TO BE SELECTING A
SMALL NUMBER OF MCEDs FOR THAT
PROGRAM.
THAT PROCESS OF SELECTION IS
UNDERWAY.
WE ARE PART OF IT, AND WE ARE
HOPING TO BE -- TO HAVE A TEST
THAT IS DEEMED TO BE COMPETITIVE
AND WORTHY OF PARTICIPATION IN
THIS VERY IMPORTANT LONG -- IT
WILL TAKE MANY YEARS, BUT
RANDOMIZED CLINICAL TRIALS TO
SHOW THAT THESE TESTS ULTIMATELY
SAVE LIVES FOR MANY DIFFERENT
CANCERS AND ALSO HAVE VALUE TO
THE HEALTHCARE SYSTEM.
OUR TEST IS DIFFERENT THAN MOST
OF THE COMPETING TESTS THAT WE
KNOW OF IN THAT IT IS MAINLY
PROTEIN-BASED.
WE DO ALSO INCLUDE SOME
INFLAMMATORY AND METABOLIC
MARKERS, AND IT'S GROWING RATHER
FAST.
WE SELL THE TEST, IT'S ON THE
MARKET, ONE TEST FOR CANCER.COM.
WE GET, OH, YOU KNOW, 15 OR SO
DIRECT CONSUMER ORDERS A DAY.
WE USE TELEMEDICINE.
THERE ARE 600 PLACES PEOPLE CAN
GET A BLOOD DRAW THROUGHOUT THE
UNITED STATES.
WE ALSO SELL TO EMPLOYERS, AND
SOME MEDICAL ORGANIZATIONS THAT
SPECIALIZE IN PREVENTION AND
LIFESTYLE MEDICINE.
AND ALSO OCCUPATIONAL HEALTH.
THE EMPLOYERS ARE TYPICALLY ONES
WHERE THEIR EMPLOYEES ARE
BELIEVED TO HAVE HIGHER
INCIDENCE IN DEATH FOR A VARIETY
OF CANCERS, SUCH AS FIRE
DEPARTMENTS.
FIRE DEPARTMENTS COMPRISE CLOSE
TO HALF OF OUR CUSTOMERS AT THIS
POINT THROUGHOUT THE UNITED
STATES.
AND WE USE MACHINE LEARNING
ALGORITHMS BUILT FROM DATA IN
PART OF THE WORLD, NAMELY THE
FAR EAST, WHERE THESE TESTS ARE
NOT JUST COMMON BUT UNIVERSAL.
AND WE HAVE DEMONSTRATED THAT
THESE ALGORITHMS SUBSTANTIALLY
IMPROVE DIAGNOSTIC ACCURACY.
OUR ADVANTAGES OVER THE GALLERY
TEST FROM GRAIL AND OTHER
EMERGING CT DNA ARE THE
PROVERBIAL BETTER, FASTER,
CHEAPER, BETTER ACCURACY FOR
EARLY STAGE CANCERS, MORE
SENSITIVE, WHICH IS WHAT YOU
WANT IN A SCREENING TEST.
AND ALSO FASTER ACCESS BY VIRTUE
OF OUR RECENT VALIDATIONS OF THE
TEST WITH CAPILLARY BLOOD, WE
ACTUALLY ARE MOVING THE TEST
INTO PHARMACY COUNTERS, AT
SUPERMARKET CHAINS.
WE HAVE ONE AGREEMENT IN PLACE
ALREADY.
IN THE SECOND QUARTER, WE EXPECT
TO HAVE THAT AT LEAST AS A
PILOT, SO EASY ACCESS THROUGH
CAPILLARY COLLECTION, EVENTUALLY
HOME-BASED, WHICH WOULD BE HARD
TO DO WITH CT DNA, WHICH
TYPICALLY REQUIRES MORE PLASMA,
AND MUCH CHEAPER.
THESE TESTS -- OUR TEST IS UNDER
$200 FOR THE BASIC VERSION,
VERSUS $1,000 FOR THE GRAIL
GALLERY TEST.
SO IT'S BETTER, FASTER, CHEAPER.
I WANT TO COME BACK TO THE
ENTITY THAT I MENTIONED IN MY
INTRODUCTION, WHAT WE CALL
CLIAX, CLINICAL LAB INNOVATION
ACCELERATOR.
WE, WORKING WITH REGULATORY
COUNCIL, HAVE COME UP WITH A
COMPLIANT MODEL THAT ALLOWS US
TO ESSENTIALLY SHARE OUR SPACE,
OUR EQUIPMENT, OUR LICENSURE,
AND THE IDEA IS THAT A COMPANY
THAT EITHER BECAUSE OF THEIR
SIZE OR THEIR GEOGRAPHY, AN
OVERSEAS COMPANY, FOR EXAMPLE,
TO COME INTO THE UNITED STATES
AND TO LEASE SPACE, TO EQUIP IT
WITH EXPENSIVE INSTRUMENTATION
FROM COMPANIES LIKE QIAGEN OR
OTHERS, TO STAFF IT WITH THE
PERSONNEL THAT ARE REQUIRED
UNDER CLIA CAN BE FORMIDABLE.
AND THE IDEA WOULD BE TO -- WE
HAVE CREATED A TURNKEY SOLUTION.
RIGHT NOW WE HAVE ONE COMPANY
FROM AUSTRALIA THAT LAUNCHED
THEIR PRODUCT THROUGH OUR CLIA
X, IT HAPPENS TO FOCUS ON
PROSTATE CANCER, BUT WE ARE
INTERESTED IN OTHERS BUT WE ARE
PARTICULARLY LOOKING FOR
COMPANIES THAT WE CAN HELP SELL
THEIR PRODUCT, THEIR TESTS TO
OUR CUSTOMERS.
OF WHICH WE NOW HAVE ABOUT
15,000, BUT THESE ARE TESTS FOR
WELLNESS PREVENTION SCREENING
EARLY DETECTION, NOT FOR PEOPLE
WITH A CONFIRMED DIAGNOSIS THAT
ARE BEING TREATED, EITHER AT A
HOSPITAL OR OUTPATIENT.
THAT IS NOT OUR FOCUS.
WE DO NOT HAVE A SALES TEAM THAT
CALLS ON MEDICAL SPECIALISTS.
SO THINGS LIKE EARLY DETECTION
OF CARDIOVASCULAR DISEASE,
ALZHEIMER'S, WE ARE VERY, VERY
INTERESTED IN NUTRITION AND FOOD
AS MEDICINE.
WAYS PEOPLE CAN IMPROVE THEIR --
BOTH THE LONGEVITY AND QUALITY
OF LIFE THROUGH A HEALTHY DIET
AND EXERCISE PROGRAM.
BIOMARKERS ASSOCIATED WITH
AGING, SUCH AS INFLAMMATORY
MARKERS AND TELOMERE LENGTH AND
THE LIKE.
THESE ARE THE PRODUCTS THAT WE
WOULD LIKE TO HELP LAUNCH AND
MARKET IN THE UNITED STATES TO
OUR CUSTOMERS FOR WELLNESS,
EARLY DETECTION PREVENTION.
AND I WOULD ALSO LIKE JUST TO IN
CLOSING, I'D BE REMISS NOT TO
POINT OUT THAT WE HAVE HAD A
LONG AND PRODUCTIVE HISTORY OF
WORKING WITH NIH AT DIFFERENT
LEVELS, SO EARLY IN OUR COMPANY
LIFE, WE HAD WHAT'S CALLED A
CRADA, COOPERATIVE RESEARCH AND
DEVELOPMENT AGREEMENT.
WE ACTUALLY -- OUR FIRST LAB WAS
IN AN NIH NCI FACILITY IN
GAITHERSBURG.
WE HAD THAT FOR ABOUT TWO YEARS.
WE ACTUALLY HAD SOME BE BENCH SE
THERE.
WE HAD LICENSE AGREEMENTS WITH
NIH AND WE HAD BEEN THE
RECIPIENT OF SEVERAL MILLION
DOLLARS OF SBIR GRANTS AND
CONTRACTS.
NOT RECENTLY.
THESE GO BACK SEVEN, EIGHT, NINE
YEARS, BUT AT VARIOUS POINTS IN
OUR TRAJECTORY, IN OUR COMPANY'S
TRAJECTORY, THEY WERE VERY
IMPORTANT.
SO LICENSE AGREEMENTS, CRADAs,
SBIR GRANTS, AND HOPEFULLY THIS
VANGUARD PROGRAM, VERY EXCITING
VANGUARD PROGRAM THAT I REFERRED
TO, WHICH IS SUPPORTED BY THE
WHITE HOUSE CANCER MOONSHOT, IS
SOMETHING ELSE THAT WE ARE
HOPING TO PARTICIPATE IN.
AND THEN FINALLY, THIS CLINICAL
LAB INNOVATION AK SE RAY TORE
CAN CERTAINLY FIT, WE HAVE HAD
INQUIRIES FROM THE NIH'S
INTRAMURAL PROGRAM.
NOTHING THAT HAS SO FAR
MATERIALIZED, BUT THIS COULD BE
SOMETHING THAT AN NIH
INVESTIGATOR THAT WOULD LIKE TO
COMMERCIALIZE THEIR ASSAY, IF
THEY BELIEVE THERE IS A MARKET,
WE WOULD LIKE TO HEAR FROM THEM.
AS WELL AS EXTRAMURAL GRANTEES
AND LICENSEES FROM THE NIH.
SO THAT CONCLUDES MY
PRESENTATION.
MY CONTACT INFORMATION MAY BE --
IS VISIBLE ON THIS SLIDE.
AND I CERTAINLY WILL LOOK
FORWARD TO ANY QUESTIONS.
THANK YOU FOR YOUR TIME THIS
AFTERNOON.
>> THANK YOU VERY MUCH,
JONATHAN.
YES, WE'LL HAVE A COUPLE
QUESTIONS AT THE END.
FOR THE MOMENT, WE'RE GOING TO
MOVE ON TO DR. TOM NUTMAN,
SENIOR INVESTIGATOR AT THE
NATIONAL INSTITUTE OF ALLERGY
AND INFECTIOUS DISEASES.
>> THANK YOU VERY MUCH.
I ASSUME YOU CAN SEE MY SLIDES.
I THINK I'M A LITTLE BIT OF A
FISH OUT OF WATER HERE IN THIS
SESSION.
BUT I'M GOING TO TALK ABOUT, I
THINK, SOME INNOVATIONS THAT WE
IDENTIFIED AND THEN HOW WE
OVERCAME WHAT I'LL CALL ROAD
BLOCKS FOR PUBLIC HEALTH
DIAGNOSTIC NEEDS AND I'M GOING
TO USE THIS -- I'M GOING TO USE
A VERY SET OF SERIOUS PARASITIC
INFECTIONS CALLED THE FILARIAL
INFECTIONS TO SORT OF ILLUSTRATE
THE PROBLEMS AND HOW ONE CAN
OVERCOME THEM FOR ULTIMATELY
POINT OF CARE DIAGNOSTICS.
SO I STUDIED AND HAVE STUDIED
FOR ALMOST MY ENTIRE CAREER
THESE NEGLECTED TROPICAL
DISEASES, AND THESE ARE
NEGLECTED NOT ONLY BY FUNDING
AGENCIES, BUT ALSO BY MOST
MINISTRIES OF HEALTH IN THE
AREAS WHERE THESE EXIST TWO OF
THE INFECTIONS I'M GOING TO TALK
ABOUT TODAY, I'LL EXPLAIN A
LITTLE BIT ABOUT WHAT THEY ARE
IN A SECOND, BUT YOU CAN SEE THE
NUMBER OF CA OF EACH OF THESE
AROUND THE WORLD AND YOU CAN SEE
THE POPULATION AT RISK, WHICH
EXCEEDS 1 BILLION PEOPLE ALSO
KNOWN AS RIVER BLINDNESS, IT'S
THE SECOND LEADING CAUSE OF
INFECTIOUS BLINDNESS AROUND THE
WORLD.
LYMPHATIC -- IS COMMONLY
REFERRED TO AS ELEPHANTIASIS
BECAUSE OF THE SORT OF CLINICAL
DEVASTATION AS SHOWN HERE,
PHOTOGRAPH THAT WAS ON THE COVER
OF "THE NEW YORK TIMES" MAGAZINE
SECTION ON THE TOP AND A WHO
STATUE IN FRONT OF WHO
HEADQUARTERS IN GENEVA SHOWING A
YOUNG BOY LEAVING AFRICAN
ELDERLY MEN TO THE FIELDS
BECAUSE THEY'VE ALL BEEN BLINDED
BY ONCO -- THE MOST DEVASTATING
CONSEQUENCES ARE ELEPHANTIASIS
AND THESE ARE CLINICAL PICTURES
SHOWN HERE.
AS YOU CAN IMAGINE, THESE HAVE
DEVASTATING CONSEQUENCES.
IF YOU LOOK AROUND THE WORLD
WHERE THESE EXIST, THEY EXIST IN
LARGELY UNDERRESOURCED LOW AND
MIDDLE INCOME COUNTRIES, AND SO
ALL DIAGNOSTICS THAT ARE BEING
USED FOR THESE TYPICALLY HAVE
LITTLE LIKELIHOOD OF PROVIDING
COMMERCIAL VALUE TO COMPANIES
THAT ARE CONSIDERED -- WHO ARE
WILLING TO COMMIT TO
COMMERCIALIZING PRODUCTS OR
MAKING THEM AT SCALE IN A
MANUFACTURABLE WAY.
AND SO LARGELY I JUST WANT TO
LAY OUT THE PROBLEMS AND ROAD
BLOCKS IN THESE NTD DIAGNOSTICS,
INCLUDE THE DISEASES AND USES
ARE EXCLUSIVELY LIMITED TO LOW
AND MIDDLE INCOME COUNTRIES, AND
THESE DIAGNOSTICS ARE UNLIKE
MOST DIAGNOSTICS BECAUSE WE'RE
NOT LOOKING AT NECESSARILY AT
ONLY THE INDIVIDUAL, DO THEY
HAVE THE INFECTION OR DO THEY
NOT.
WE'RE OFTEN NEEDING TO ASSESS
ENTIRE DISTRICTS OF POPULATIONS
OR COMMUNITIES TO UNDERSTAND THE
PREVALENCE OF THESE INFECTIONS
AND THEN HOW TO DEAL WITH THEM.
AND THE ONLY TIME THAT WE USE
THEM AT THE INDIVIDUAL LEVEL ARE
IN THESE RESEARCH-RICH
COUNTRIES, SUCH AS THE U.S., AND
WE DO USE THEM HERE BECAUSE
THESE DO AFFECT TRAVELERS,
REFUGEES WHO NEED TESTING.
MOTOR COMMERCIAL ENT TEES ARE
GENERALLY UNWILLING TO
UNDERWRITE THE RESEARCH COST TO
MAKE A MANUFACTURABLE DIAGNOSTIC
DEVICE, AND AS SORT OF A --
WE'LL JUST SORT OF STAND ON A
SOAP BOX A LITTLE BIT TO SAY
THAT UNLIKE THE PHARMACEUTICAL
COMPANIES SUCH AS MERCK OR GSK
OR PFIZER THAT HAVE LARGE
DONATION PROGRAMS FOR MASS DRUG
ADMINISTRATION CAMPAIGNS ACROSS
THE WORLD, LARGE DIAGNOSTIC
FIRMS HAVE NOT GENERALLY BEEN
WILLING TO OVERLOOK COMMERCIAL
CONSTRAINTS.
BUT I'M GOING TO TELL YOU A
STORY ABOUT HOW WE'VE OVERCOME
SOME OF THESE.
AND THE STORY GOES BACK TO
REALLY THE 1980s, 1991,
REPORTED IN SCIENCE, THE
IDENTIFICATION OF AN IMMUNOGENIC
ONCOSPECIFIC ANTIGEN THAT COULD
BE USED AS A SPECIFIC AND EARLY
MARKER OF INFECTION, AND WE
WROTE IN THE FINAL PARAGRAPH OF
THIS THAT THE POTENTIAL USES OF
THIS WOULD BE TO DIAGNOSE
INDIVIDUALS TO DO PRIMARY
SURVEILLANCE IN AREAS OF UNKN
UNKNOWN -- TO DETECT EARLY
INFECTIONS OR AS A MARKER OF
TRANSMISSION, AND ULTIMATELY TO
BE USED NATIONWIDE TO CERTIFY
THAT SOME OF THESE INFECTIONS
HAVE BEEN ELIMINATED.
WE'RE IN THE PROCESS OF -- WE'VE
DONE THIS ALREADY IN SEVERAL
COUNTRIES AROUND THE WORLD.
AND SO IN 1991, WE IDENTIFIED
THIS AND PUBLISHED THIS MARKER,
AND IT TOOK US 8 OR 9 YEARS TO
FIND ANY COMMERCIAL GROUP WHO
WAS WILLING TO EVEN MAKE A
PROTOTYPE, BUT SHOWN HERE IS A
COMPANY FROM AUSTRALIA AT THE
TIME, AMRAD ICT, AND THEY
DEVELOPED -- PIGGY BACKED, IN A
MATTER OF TWO OR THREE WEEKS,
FROM AN EXISTING TEST THAT THEY
HAD DONE, THEY PIGGY BACKED THIS
ANTIGEN AND CAME UP WITH
SOMETHING THAT WORKED
EXTRAORDINARILY WELL.
THEY PUT -- DID A PRODUCTION RUN
OF 20,000 AND WE DID FIELD
TESTING IN AFRICA AND SHOWED THE
SENSITIVITY WAS HIGH,
SPECIFICITY WAS GREATER THAN
98%.
IT PICKED UP ALL-COMERS WHO WERE
INFECTED, TRULY INFECTED, AND IT
WAS USEFUL IN ASSESSING REPREU
DESENSE OF INFECTION AND SUCCESS
OF THESE CONTROL PROGRAMS IN
LARGE FIELD TESTINGS ACROSS
AFRICA AND THE AMERICAS.
BUT HERE'S THE PROBLEM.
IN 2001, BINEX BOUGHT ANRAB AND
THEY MADE A COMMERCIAL DECISION
THAT THIS WAS NOT GOING TO BE
ANYTHING THAT WAS GOING TO FIT
INTO A COMMERCIAL -- THEIR SORT
OF FUTURE COMMERCIAL ROLES AND
THEY DISCARDED IT.
AND AS YOU ARE ALL WELL AWARE IN
THE DIAGNOSTIC WORLD AND THE
PHARMACEUTICAL WORLD AND
EVERYWHERE ELSE, THERE ARE LOTS
OF MERGERS AND ACQUISITIONS
BECAUSE I'M GOING TO GET BACK TO
THIS IN A SECOND, BUT OLE.
AR BOUGHT BINEX IN 2005, ABBOTT
BOUGHT ALEER IN 2017, AND THEN
ABBOTT BOUGHT STANDARD
DIAGNOSTICS IN 2021.
AND THIS IS GOING TO BE
IMPORTANT AS I GET TO SOME OF MY
LATER DISCUSSION.
SO FORTUNATELY FOR US, 10 YEARS
OR 11 YEARS LATER, THE BILL AND
MELINDA GATES FOUNDATION WAS
WILLING TO PARTNER WITH PATH AND
US TO COME UP WITH A WAY TO GET
TO COMMERCIALIZATION OF A VERY
USEFUL PRODUCT, AND SO THEY
PROVIDED MONEY TO PATH TO DO ALL
OF THE LANDSCAPING AND TO US AND
THEM TO DO ALL OF THE RESEARCH
AND DEVELOPMENT AND VALIDATION
TO ULTIMATELY BE ABLE TO
TRANSFER THIS INITIAL LAB BASED
TEST AND FORMALLY COMMERCIALIZED
TEST TO A KIND OF LONG-STANDING
COMMERCIAL PARTNER, AND THEY
WERE ABLE TO NEGOTIATE
COMMERCIAL TERMS SUCH THAT IT
COULD BE SOLD AT COST, PLUS A
FEW CENTS, TO WHO OR MINISTRIES
OF HEALTH OR NGOs AND THE WAY
THEY WERE ABLE TO SELL THIS WAS
TO GUARANTEE PROCUREMENT ON A
YEARLY BASIS, A CERTAIN NUMBER
OF TESTS PER YEAR, SO EVEN IF A
COMPANY IS ONLY MAKING A FEW
CENTS ON THIS, IF YOU CAN SELL A
MILLION OF THEM, THEN AT LEAST
YOU'RE GOING TO COVER YOUR COSTS
ON SOME OF THE OTHER THINGS.
AND THERE WAS AN AGREEMENT TO
ALLOW THE COMPANIES TO SELL
COMMERCIALLY THE PRODUCTS AT
MARKET PRICES IF NEEDED IN MORE
RESOURCED AREAS.
WE WERE REALLY LUCKY THAT THIS
PRIVATE PARTNER, PRIVATE PUBLIC
PARTNERSHIP WAS SUCCESSFUL AND
WE WERE ABLE TO MOVE THIS INTO
COMMERCIAL MANUFACTURING SPACE
WITH STANDARD DIAGNOSTICS IN
KOREA THAT HAD -- THIS IS JUST A
PICTURE OF THIS, AND THE POINT
ABOUT THIS WAS THAT IT WAS AN
RDT WITH A VERY LONG READ WINDOW
AND END POINT STABILITY.
YOU CAN IMAGINE SINCE THESE
TESTS ARE DEPLOYED IN RURAL AR
AREAS OF AFRICA WHERE THERE'S NO
ELECTRICITY THAT HAVING A TEST
STABLE AT ROOM TEMPERATURE OR IN
HIGH TEMPERATURE FOR LONG SHELF
LIFE AND THAT THE RESULTS COULD
BE STABLE -- LARGELY
INDEFINITELY, WAS AN IMPORTANT
PART AND ULTIMATELY IN 2015 WAS
LAUNCHED AS -- IGG 4 AND TO
DATE, MILLIONS HAVE BEEN
UTILIZED ACROSS THE WORLD.
AROUND THE SAME TIME, WE HAD
DISCOVERED AND PUBLISHED IN 2012
A SECOND ANTIGEN FOR THIS
LYMPHATIC FI FILARIASIS THAT HAD
THE SAME KINDS OF PROPERTIES,
HIGH SENSITIVITY, HIGH
SPECIFICITY AND BECAUSE A LOT OF
THESE INFECTIONS EXIST TOGETHER
IN THE SAME AREA OF COENDEMIC,
WE WERE ABLE TO COMMERCIALIZE
BOTH AND -- WHICH WAS
RESEARCH-ONLY AS WELL AS TO ADD
THIS ANTIGEN TO THE SD BIOLINE
PORTFOLIO, AND NOW WE HAD A
BIPLEX TEST COMMERCIALLY
AVAILABLE, SOLD AT COST, THAT
COULD DETECT BOTH ONC
ONCHOCERCIASIS -- SPECIFIC
ANTIGEN.
SO I'M GOING TO END UP SHORTLY
ON THE LESSONS LEARNED AND
CAUTIONS, I'D LIKE TO SORT OF
PUT OUT THERE, DIAGNOSTICS FOR
PUBLIC HEALTH DECISION-MAKING
WHICH IS WHAT MOST OF THESE ARE
AND GIVES YOU THE VERY LARGE
SORT OF POPULATION -- TARGET
POPULATION TO WHICH THESE TESTS
ARE GOING TO BE USED, ARE
DIFFICULT SELL TO MOST COMPAN
COMPANIES.
AS YOU CAN SEE WE WENT FROM 1989
ESSENTIALLY TO 2015 BEFORE A
VERY USABLE TEST WAS ACTUALLY
ABLE TO BE PUT OUT THERE IN
LARGE SCALE, SO MAKING THE POINT
THAT IT DOES REQUIRE PATIENTS IF
YOU'RE IN THIS SPACE.
THE OTHER THING I THINK IS
REALLY IMPORTANT TO MAKE SURE
THAT THE USE CASES AND THE
TARGET PROFILES ARE DEFINED AND
CAN BE MET IN ADVANCE OF
COMMERCIALIZATION SO THAT WHEN
THERE IS A COMMERCIALIZED
PRODUCT, YOU CAN ACTUALLY GO OUT
THERE AND GET A BUY-IN FROM
PEOPLE WHO NEED IT AND I THINK
THIS DOESN'T COME UP OFTEN,
PARTICULARLY AS WE'RE TALKING
TODAY, BUT TO ENSURE SUSTA
SUSTAINABILITY GIVEN MERGERS AND
ACQUISITIONS.
SO I MENTIONED IN THAT EARLIER
SLIDE THAT SD WAS PURCHASED BY
ABBOTT, AND WE DON'T HAVE ANY
GUARANTEE THAT -- IN ANOTHER
YEAR OR SO, WHEN OUR INITIAL
SORT OF AGREEMENT ENDS, WHETHER
A VERY LARGE COMPANY LIKE THIS
IS GOING TO BE WILLING TO TAKE
TO DO SOMETHING THAT IS OF GREAT
BENEFIT TO THE WORLD BUT NOT
NECESSARILY TO THE COMPANY'S
BOTTOM LINE.
AS I'M GOING TO MAKE IN THE NEXT
SLIDE, DON'T IGNORE THESE
SMALLER COMPANIES BECAUSE I
THINK I'M GOING TO SHOW YOU SOME
EXAMPLES OF WHERE THAT HAS MADE
A BIG DIFFERENCE.
SO THINGS IN MY OWN GROUP I'M
INVOLVED IN AND SOME OF WHICH
HAVE GONE QUITE A LONG WAY TO
COMMERCIALIZATION, WE HAVE
ANOTHER PARASITE WHERE
COMMERCIALIZED PRODUCT HAS BEEN
DEVELOPED, THERE'S NEW SECOND
GENERATIONS OF THESE RUTs THAT
I'VE JUST DISCUSSED, AND THEN
LISTED BELOW ARE SOME OTHER
INTERACTIONS THAT ARE COMING TO
THE MARKETPLACE SOON, AND I WILL
MENTION THAT THOUGH I TALKED
ABOUT ANTIBODY DETECTION HERE
TODAY, WE ARE WORKING ON POINT
OF CARE NUCLEIC ACID TESTS AND
HAVE MULTIPLE PARTNERS FOR POINT
OF CARE HIGHLY SENSITIVE, HIGHLY
SPECIFIC DNA OR OTHER -- OR
URINE OR CSF FOR A VARIETY OF
DIFFERENT SYNDROMES AS WELL AS
OTHER PARASITIC INFECTIONS.
WITH THAT, I'LL STOP AND JUST
NOTE THAT A NUMBER OF --
OBVIOUSLY A NUMBER OF PEOPLE
HAVE BEEN INVOLVED IN MANY OF
THESE DIFFERENT PROJECTS PROJECM
LISTING HERE MY MAJOR
COLLABORATORS ON THE PROJECT.
WITH THAT, I'LL STOP.
>> THANK YOU, TOM.
WE HAVE A QUESTION FOR YOU AS
WELL BUT WE'LL HOLD IT UNTIL THE
END.
SO ONE THING THAT THIS PANEL,
AMONG MANY THINGS, THAT IS SO
WONDERFULLY DEMONSTRATES IS THE
DIFFERENT SIZES AND STAGES OF
THE COMPANIES THAT WE WORK WITH,
YOU HAVE ONE THAT'S GLOBAL AND
WORLDWIDE LIKE QIAGEN, YOU HAVE
ONE THAT HAS OBTAINED A HUGE
AMOUNT OF SUCCESS IN ABOUT A
DECADE AND REALLY BECOME A A
REGIONAL PLAYER, AND THAT'S
2020, AND NOW WE HAVE SOMETHING
ON THE EARLIER SIDE AND THAT IS
RACHEL ZAYAS, FOUNDER AND CEO OF
AGED DIAGNOSTICS.
>> THANK YOU, MICHAEL.
APPRECIATE IT.
ALL RIGHT.
HELLO, GOOD AFTERNOON.
MY NAME IS RACHEL ZAYAS, FOUNDER
AND CEO OF AGED DIAGNOSTICS.
WHEN I WAS WORKING AT MIT IN
CANCER RESEARCH AT THE KOCH
INSTITUTE, I REALIZED THE TOOLS
WE WERE USING WERE NOT BEING
WELL TRANSLATED INTO THE CLINIC.
I SAW AN OPPORTUNITY TO IMPROVE
THE LIVES OF PATIENTS.
OUR TEAM IS WORKING TOGETHER TO
CREATE THE FIRST ACCURATE BLOOD
TEST FOR FATTY LIVER DISEASE.
EARLY DETECTION, INTERVENTION
AND IMPROVED OUTCOMES FOR
PATIENTS AND THEIR FAMILIES.
DID YOU KNOW ONE IN THREE
AMERICANS OR 100 MILLION PEOPLE
IN THE UNITED STATES HAVE FATTY
LIVER DISEASE?
THIS DISEASE IS NOT ASSOCIATED
WITH ALCOHOL CONSUMPTION, BUT
RATHER DIABETES, OBESITY AND
METABOLIC SYNDROME.
IT IS CALLED NON-ALCOHOLIC STATA
HEPATITIS OR NASH.
AT LATER STAGES IT'S NO LONGER
TREATABLE OR REVERSIBLE.
THERE ARE VERY FEW EFFECTIVE
NONINVASIVE DIAGNOSTIC TOOLS
THAT CAN DIFFERENTIATE THE
BENIGN OR ADVANCED FORM.
A PICTURE IS WORTH A THOUSAND
WORDS SO I SHOW THIS MAP TO
PAINT THE GLOBAL INSTANCE OF
FATTY LIVER DISEASE.
UNITED STATES IS LEADING THIS
EPIDEMIC WITH MORE THAN 33% OF
THE U.S. POPULATION BEING HIGH
RISK, THE EUROPEAN UNION,
SOUTHEAST ASIA AND AUSTRALIA ARE
FOLLOWING CLOSE BEHIND.
SO THERE ARE TWO TYPES OF FATTY
LIVER DISEASE.
FIRST THERE'S A BENIGN FORM OF
LIVER DISEASE OF WHICH
80 MILLION PATIENTS IN THE
UNITED STATES HAVE THIS BENIGN
FORM.
THEN THERE'S NON-ALCOHOLIC,
NASH.
20 MILLION PATIENTS IN THE
UNITED STATES HAVE NASH.
THE CHALLENGE FOR PHYSICIANS IS
THAT THERE ARE ZERO TOOLS THAT
CAN DIFFERENTIATE THE BENIGN
FROM ADVANCED FORM OF FATTY
LIVER DISEASE.
IMAGING TOOLS ARE INACCURATE.
IF THERE IS SIGNIFICANT FAT OR
FLUID BETWEEN THE CHEST WALL AND
THE LIVER THESE TOOLS HAVE BEEN
KNOWN TO HAVE FAILED RESULTS IN
UP TO 60% OF PATIENTS.
THE SOLE DIAGNOSTIC TEST IS A
LIVER BIOPSY.
THESE ARE EXPENSIVE, INVASIVE,
PRO TO -- AND BLEEDING,
THEREFORE, THEY CANNOT SERVE THE
POPULATION AT LARGE.
AT AGED, WE'RE DEVELOPING THE
FIRST ACCURATE BLOOD TEST FOR
NASH AND A SECOND TOOL THAT CAN
STAGE LIVER FIBROSIS.
OUR TOOLS WILL HELP
HEPATOLOGISTS IMPROVE PATIENT
OUTCOMES, REDUCE THE BURDEN ON
HEALTH INSURERS AND AID IN EARLY
DETECTION AND INTERVENTION.
HERE'S HOW OUR TECHNOLOGY WORKS.
WE TAKE A PATIENT BLOOD SAMPLE
AND WE ISOLATE VERY SPECIFIC
BIOMARCS ASSOCIATED WITH THE
EPIGENOME, THEN WE TREAT THE
SAMPLE WITH THE SET OF
NASH-SPECIFIC PROBES AND A SET
OF LIVER DAMAGE PROBES.
WE APPLY TARGETED NEXT
GENERATION SEQUENCING ASSESSMENT
TO QUANTIFY THE CONCENTRATION OF
THESE BIOMARKERS IN CIRCULATION.
WE CAN STATE WITH HIGH CLINICAL
ACCURACY IF THE PERSON HAS NASH
AND WHAT STATE OF LIVER FIBROSIS
THEY HAVE.
THERE ARE THREE CORE ASPECTS TO
OUR TECHNOLOGY.
FIRST AT FOREMOST WE HAVE THE
FIRST TOOL THAT CAN ACCURATELY
DIFFERENTIATE SIMPLE STAY PTOSIS
FROM NASH FROM PERIPHERAL BLOOD.
SECOND AND OF EQUAL IMPORTANCE,
WE CAN STAGE LIVER FIBROSIS.
THERE ARE FOUR STAGES OF LIVER
FIBROSIS AND AFTER STAGE TWO,
THIS INCREASES BOTH HEPATIC AND
CARDIOVASCULAR MANIFESTATIONS BY
UP TO 80% SO IT'S CLINICALLY
RELEVANT TO DIAGNOSE NASH AND
STAGED FIBROSIS IN THE SAME
PATIENT AT THE SAME TIME.
LAST BUT NOT LEAST, WE CAN
EXCLUDE OTHER FORMS OF CHRONIC
LIVER DISEASE BY TARGETING
REGIONS THAT ARE ONLY FOUND IN
NASH AND ONLY FOUND IN THE
LIVER.
THE MARKET OPPORTUNITY IS VAST
AND GROWING.
GLOBALLY THERE ARE MORE THAN
2 BILLION PATIENTS CONSIDERED
HIGH RISK AND REQUIRE ROUTINE
LIVER SCREENING.
-- SPEND MORE THAN $100 BILLION
ON DIRECT MANAGEMENT FOR THIS
SPECIFIC TYPE OF LIVER DISEASE.
WHICH EQUATES TO MORE THAN A
$27 BILLION MARKET OPPORTUNITY.
WE HAVE MULTIPLE PATENTS PENDING
BOTH ON THE BIOMARKERS AS WELL
AS THE METHODS TO ASSESS THESE
BIOMARKERS SYNTHETICALLY IN
CIRCULATION.
OUR COMPETITIVE ADVANTAGE IS
THAT WE -- FIRST ACCURATE BLOOD
TEST FOR NASH.
WE'D BE LESS EXPENSIVE THAN THE
GOLD STANDARD WHICH ARE LIVER
BIOPSIES AS WELL AS MOST
EXPENSIVE IMAGING MODALITIES.
WE EXPECT TO BE THE MOST
ACCURATE TOOL FOR DECADES TO
COME BY TARGETING HIGHLY
INNOVATIVE GENETIC REGIONS.
SO WE'VE HAD EXCITING TRACTION
TO DATE.
WE HAD RECEIVED A GRANT FROM THE
NATIONAL SCIENCE FOUNDATION IN
LATE 2018 TO CONDUCT CUSTOMER
DISCOVERY TO VALIDATE PRODUCT
MARKET FIT.
ONCE AGAIN WE HAVE MULTIPLE
PATENTS PENDING.
IN SOME OF OUR EARLY YEARS OF
RESEARCH AND DEVELOPMENT, WE
UTILIZED OPEN SOURCE DATASETS
FROM NIH AND THE CANCER GENOMICS
CLOUD TO BE ABLE TO DETERMINE IF
OUR BIOMARKERS WERE EFFICACIOUS
EVEN DIRECTLY ON THE LIVER.
WE'VE BEEN FUNDED BY
HEALTHWORKS.
THIS IS THE INVESTMENT ARM OF
CAREFIRST BLUE CROSS/BLUE
SHIELD.
WE PRESENTED WORK AT THE ANNUAL
LIVER DISEASE CONFERENCE AND
PUBLISHED WORK IN ABSTRACT FORM
IN HEPATOLOGY.
IN 2021, WE RECEIVED OUR FIRST
FINANCING ROUND, AND THIS
ALLOWED US TO CONDUCT A PILOT
STUDY IN PERIPHERAL BLOOD.
SO TO DATE, WE'VE CONDUCTED
SEVERAL PILOT STUDIES AND
IDENTIFIED A SET OF BIOMARKERS
AND HAVE BETWEEN 90 AND 90%
EFFICACY, DIFFERENTIATING
BETWEEN THE BENIGN AND ADVANCED
FORM OF FATTY LIVER DISEASE.
WE'VE RECENTLY MOVED INTO TEST
METHOD VERIFICATION, WHERE WE'RE
EXPANDING THE SAMPLE SIZE TO 500
PATIENT SAMPLES.
WE'VE RECENTLY PARTNERED WITH
THE HENRY JACKSON FOUNDATION.
THIS IS A CONGRESSIONALLY
MANDATED NON-PROFIT FOCUSED ON
THE ADVANCEMENT OF U.S. MILITARY
MEDICINE.
OUR HEADQUARTERS ARE SITUATED
OUT OF HJF AND THIS HAS HELPED
US TO UTILIZE RESOURCES WITHIN
DOD.
WE HAVE MULTIPLE CRADAs AND
MATERIAL TRANSFER AGREEMENTS
WITH WALTER REED MILITARY
CENTER, INCLUDING THE
GASTROENTEROLOGY DEPARTMENT AS
WELL AS THE AMERICAN GENOME
CENTER.
WE PLAN TO PURSUE A LARGER
CLINICAL TRIAL NEXT YEAR AND
THEN PURSUE BOTH PAYOR
REIMBURSEMENT AND REGULATORY
HURDLES.
WE PLAN TO LAUNCH AS A SERVICE
AS A LAB DEVELOPED TEST BY THE
END OF NEXT YEAR.
SO WHERE THE TEAM PLANS TO TAKE
THIS TECHNOLOGY TO MARKET, WE
HAVE 100 YEARS IN HEPATOLOGY, 75
YEARS IN BUSINESS, 40 YEARS IN
GENETICS.
WE'VE HAD FIVE PREVIOUS EXITS
AND CLOSED ON MORE THAN
825 MILLION IN FUNDING IN OUR
PREVIOUS PURSUITS.
SO ONCE AGAIN OUR TOOLS DO NOT
REQUIRE FDA APPROVAL TO GET TO
MARKET BUT RATHER CLIA APPROVAL
IN WHICH WE CAN LAUNCH AS A
LAB-DEVELOPED TEST.
WE'VE HAD TWO STUDIES IN
PERIPHERAL BLOOD THAT WE'VE
CONDUCT AND WE HAVE TWO MORE
STUDIES UNDERWAY WITH THE
ADDITIONAL SAMPLE SIZE FROM
ABOUT 2,000 PATIENT SAMPLES.
WE NOD ABOUT -- WE PLAN TO
LAUNCH BY Q3 OF NEXT YEAR.
SO OUR TOOLS CAN BE REIMBURSED
AT A RATE BETWEEN 650 TO $1,500
PER PATIENT PER TOOL.
WE UTILIZE A COMBINATION OF
THESE FOR REIMBURSEMENT AND WE
LAUNCH IN THE DC, MARYLAND,
VIRGINIA AREA.
WE ARE CURRENTLY RAISING CAPITAL
TO REACH THE FOLLOWING
MILESTONES.
TEST METHOD VERIFICATION WHERE
WE EXPAND THE SAMPLE SIZE TO 500
MORE PATIENT SAMPLES, TEST
METHOD OPTIMIZATION WHERE WE
COMPARE A COMBINATION OF
TARGETED BIOMARKERS AND LAST BUT
NOT LEAST, THE ROLE BUSINESS
DEVELOPMENT MILESTONES INCLUDING
CLINICAL AND REGULATORY
PURSUITS.
SO WE ARE HUNGRY, HUMBLE AND
YEARNING FOR PROGRESS.
OUR MISSION IS NOT ONLY TO HELP
PATIENTS AGE BUT LOOK BACK AND
SAY THAT THEY HAVE AGED
GRACEFULLY.
THANK YOU.
>> THANK YOU VERY MUCH, RACHEL.
SO I'D LIKE TO HAVE EVERYBODY
BACK ON AND I'LL GO THROUGH SOME
QUESTIONS.
SOME OF THESE ARE GOING TO BE
DIRECTED AT SPECIFIC PEOPLE,
HOWEVER, IF YOU HAVE ADDITIONAL
COMMENTS, PLEASE DO WEIGH IN.
SO TO START OFF FOR DAN, HIV
DIAGNOSTICS, IS THERE ANY
CHALLENGE THAT YOU'VE HAD IN
TRYING TO GARNER INTEREST FROM
THE OUTSIDE COMMUNITY AND THE
PERCEPTION/MISPERCEPTION THAT
THESE TREATMENTS FOR AIDS, HIV,
IT'S A WELL MANAGED CHRONIC
CONDITION SO WHY IS SO MUCH MORE
BEING DONE ON IT?
I'M NOT ASKING YOU TO JUSTIFY
IT.
CAN YOU SAY HOW YOU -- YOU KNOW,
WHEN YOU APPROACH OUTSIDE
PARTNERS TO WORK WITH HOW YOU
COMMUNICATE WHAT A MAJOR HEALTH
PROBLEM THIS REMAINS?
>> SURE, YEAH, IT'S ABSOLUTELY
TRUE.
THERE'S PLENTY OF GOOD
DIAGNOSTIC KITS FOR HIV, AND I
WOULD SAY TO LOTS OF PEOPLE,
IT'S FAIRLY WELL MANAGED AS LONG
AS YOU HAVE ENOUGH MONEY.
AND YOU'RE FORTUNATE ENOUGH TO
LIVE IN A WEALTHY COUNTRY SUCH
AS OURS, OR EUROPE, OR JAPAN OR
CHINA.
BUT IF YOU GO TO A DIFFERENT
LOCALE IN THE WORLD, IT'S NOT SO
WELL MANAGED.
THE IS THAT TIS T STATISTICS I K
TO ARE IN AFRICA, IN PARTICULAR
WHERE THE DISEASE IS REALLY
BORNE BY YOUNG WOMEN IN A LOT OF
WAYS, IN WHICH CASE IT'S YOUNG
WOMEN WHO ARE PURSUED BY OLDER
MEN, AND THOSE OLDER MEN WILL
PASS THE DISEASE ON.
AND SO ANYTHING YOU CAN DO TO
SORT OF, LIKE, PREVENT AND BLOCK
THE PROGRESSION OF THAT CYCLE IS
GOING TO BE A BENEFIT.
YES, IT'S CERTAINLY AN UPHILL
BATTLE TO FIND PEOPLE WILLING TO
SORT OF TAKE ON A DIFFERENT
APPROACH TO HIV DIAGNOSTICS.
I THINK THERE'S INTEREST THERE.
I THINK I'LL KIND OF HIGHLIGHT
SOMETHING THAT TOM WAS
MENTIONING TO, WHICH WAS THAT --
YEAH, THERE'S REALLY NOT MUCH OF
A COMMERCIAL INCENTIVE A LOT OF
TIMES BECAUSE PROFITS ARE
ESSENTIAL FOR COMPANIES.
THAT BEING SAID, I THINK ALSO
FOR ME, I TRY TO CAST IT AS WELL
AS SORT OF A MORE GLOBAL
PLATFORM THAT ONE COULD
POTENTIALLY BUILD ON FOR OTHER
THINGS AS WELL.
IF THERE'S AN INTEREST TO GO IN
A NOVEL DIRECTION.
SO IT'S JUST SORT OF A
COMBINATION OF DIFFERENT THINGS,
AND I'M SURE, TOM, YOU'VE HAD
SORT OF SIMILAR EXPERIENCES AS
WELL.
>> CERTAINLY AGREE WITH WHAT
DANIEL HAS SAID, BUT I THINK
THIS ALSO REALLY LEADS INTO SORT
OF WHAT'S THE ECONOMIC MODEL.
AND ALSO WHAT'S THE ACTUAL
UTILITY.
WE PUT THIS SESSION AS
DIAGNOSTICS, BUT THERE'S
ACTUALLY SUBGROUPINGS IN TERMS
OF HOW THE ON-LABEL INDICATIONS
ARE USED.
IS IT A DIAGNOSTIC, IS IT A
SCREENING ASI, ASSAY, MONITORIG
ASSAY.
EACH OF THOSE TYPES OF ASSAYS
RUNS A SORT OF CLINICAL TRIAL
EXPRESS.
THE QUANTIFERON TB ASSAY, FOR
EXAMPLE, IN THE UNITED STATES
HAS AN ON-LABEL INDICATION FOR
TB DIAGNOSIS.
HOWEVER, THE U.S. CDC AND THE
WORLD HEALTH ORGANIZATION
RECOGNIZE AND RECOMMEND THAT
THIS PRODUCT BE USED FOR PUBLIC
HEALTH SCREENING PURPOSES.
WE AS A MANUFACTURER CANNOT
ADVERTISE FOR OFF-LABEL USES,
BUT WE CAN CERTAINLY SELL TO THE
PRACTITIONERS AND LABS WHO MAY
CHOOSE TO USE IT FOR THEIR OWN
PURPOSES AND THINGS ON HERE.
GOING BACK TO DAN'S CASE IN
TERMS OF HIV, I WOULD SAY YEAH,
THIS IS ACTUALLY A VERY DYNAMIC
AREA, THE FACT THAT IT HAS
BECOME A CHRONIC DISEASE IN THE
FIRST WORLD AND THE CIRCUMSTANCE
THAT DAN APPLIES INTO THE
EMERGING WORLD CERTAINLY IS A
REASON FOR DOING MUCH WIDE EARLY
TESTING, NOT FOR DIAGNOSIS, BUT
FOR IDENTIFYING THE PEOPLE WHO
NEED TO BE IN MANY WAYS ISOLATED
SOCIALLY OR WHATEVER WAY TO
PREVENT THAT FROM BEING
TRANSMITTED AND EXPANDING UPON
THAT EPIDEMIC.
THE EXPANSION AND THE
EPIDEMIOLOGY WHERE DIAGNOSIS
INTERPLAYS WITH THAT IS AN
IMPORTANT PART OF THE DYNAMIC IN
DIFFERENT REGIONS OF THE WORLD.
>> TOM, DO YOU WANT TO WEIGH IN
ON YOUR EXPERIENCE WITH
IMPORTANT GLOBAL MEDICAL NEEDS
THAT ARE NOT GOING TO BE ALL IN
U.S. MARKET --
>> RIGHT, I THINK YOU BOTH SORT
OF MENTIONED THE ISSUE, THAT IN
ALL THE TPPs, FOR EXAMPLE, FOR
MANY OF THESE PUBLIC HEALTH
NEEDS AND DIAGNOSTICS, BESIDES
BEING -- YOU KNOW, HAVING A
HIGH DEGREE OF SENSITIVITY AND
SPECIFICITY AND POSITIVE
PREDICTIVE VALUE, THE OTHER HAS
TO DO WITH THE FACT THAT -- HAS
TO DO WITH COST AND A COST HAS
TO BE LESS THAN, YOU KNOW,
IDEALLY LESS THAN A DOLLAR PER
TEST, AND ACCEPTABLE IS, YOU
KNOW, $2.
AND SO IN GENERAL, I'M STILL A
BELIEVER THAT IT IS INCUMBENT
UPON THE BIG MANUFACTURERS WHO
ARE MAKING BILLIONS AND BILLIONS
OF DOLLARS AS YOU POINTED OUT
THAT IN SOME WAYS THAT THEY
UTILIZE SOME OF THAT PROFIT TO,
YOU KNOW, MAKE A PRODUCT
AVAILABLE WHERE IT'S NEEDED.
AND NOT TO SAY THAT IT SHOULD BE
AT THE EXPENSE OF THINGS THAT
YOU'RE DOING, BUT I THINK WE'RE
SPENDING A LOT OF TIME AND
EFFORT TROYING TO DEVELOP, YOU
KNOW, POINT OF CARE NUCLEIC ACID
AMPLIFICATION TESTS YOU CAN GET
WITHOUT ANY INSTRUMENTATION AND
WITHOUT ANY MACHINES, AND WE CAN
DO THIS.
AND I SORT OF POINT THIS OUT TO
FUNDERS AND OTHER THINGS, AND
IT'S IN THE CONTEXT OF HIV.
THERE'S NOT A CORNER OF AFRICA
WHERE YOU CAN'T GET AN HIV VIRAL
LOAD.
SO WHY CAN'T WE UTILIZE, YOU
KNOW, MACHINERY AND THE OTHER
STUFF THAT IS OUT THERE TO TAKE
SOME OF THESE -- LET'S CALL IT
BETTER TESTS, THINGS THAT ARE
GOING TO WORK, AND EVEN USE
EXISTING INFRASTRUCTURE IF WE
HAVE TO.
I DO BELIEVE THAT THERE'S A
GREAT NEED TO SORT OF MAKE SOME
OF THESE, YOU KNOW, HUGELY
BENEFICIAL SORTS OF THINGS
AVAILABLE TO PEOPLE, AND WHEN
YOU POINT OUT WITH FATTY LIVER,
FOR EXAMPLE, PEOPLE THINK, OH,
YEAH, THIS IS JUST A DISEASE,
YOU KNOW, OF HIGH-INCOME
COUNTRIES, BUT NOBODY'S EVER
LOOKED, YOU KNOW, IN THE PLACES
WHERE THERE ARE MILLIONS AND
MILLIONS OF OTHER PEOPLE.
SO I DO THINK THAT WE JUST HAVE
TO HAVE A GLOBAL REACH IF WE
CAN.
>> THAT'S TRUE.
ONE THING I'D LIKE TO MENTION
IS, AND ESPECIALLY DAN AND TOM'S
WORK POINTS TO IS THAT WE DO
HAVE A MISSION FOCUS ON GLOBAL
HEALTH RATHER THAN, YOU KNOW,
JUST THE BLOCKBUSTER MARKETS.
AND WE DO WORK WITH FOUNDATIONS
AND NON-PROFIT COMPANIES WHO ARE
TRYING TO ADDRESS GLOBAL MEDICAL
NEEDS AND HAVE THE CHALLENGE
THAT THEY'RE GOING AFTER THINGS
WHICH ARE GLOBALLY IMPORTANT,
BUT NOT GOING TO, YOU KNOW, HAVE
A GREAT RETURN TO ANY INVESTORS.
AND SO THEY CAN ALSO LOOK TO NIH
AS A VERY WILLING PARTNER IN
THESE TYPES OF -- IN THESE TYPES
OF CIRCUMSTANCES.
GO AHEAD, TOM.
>> CAN I JUST POINT OUT
SOMETHING?
I THINK IT WAS BROUGHT UP AS
WELL BY OUR COLLEAGUES FROM
MARYLAND.
YOU KNOW, A LOT OF THE -- WE'LL
JUST CALL IT INTRAMURAL BASE
DISCOVERY HAS CERTAINLY BEEN
USED AS A NIDUS FOR SBIR GRANTS
BY BIOTECH AND STARTUPS AND
OTHER SMALL COMPANIES WITH THE
IDEA THAT IT CAN ACTUALLY GET
THEM OVER THE HURDLE TO SORT OF
SHOW THAT THEY CAN GET A PRODUCT
TOWARDS COMMERCIALIZATION AND
THEN ALLOW THEM TO GO FOR
ADDITIONAL, YOU KNOW, ADDITIONAL
FUNDING, UNDERWRITING IN SOME
OTHER WAY.
SO I JUST THINK -- I THINK WE
CERTAINLY HAVE BEEN INVOLVED AND
IT SOUNDS LIKE, YOU KNOW, OTHERS
HAVE -- ON THE CALL HAVE BEEN IN
SOME WAYS BENEFITED FROM SOME OF
THAT INTERACTION.
>> IF I COULD ALSO COMMENT ON
THIS, THIS IS AN IMPORTANT
QUESTION, AND THAT IS, YOU KNOW,
THE UNMET NEED IN SERVING
DIVERSE WORLDWIDE COMMUNITIES IS
OBVIOUSLY THERE.
THE CHALLENGE FOR COMPANIES IS
THAT THEY HAVE A FIDUCIARY DUTY
TO THEIR SHA SHAREHOLDERS.
NOW, IN THE CASE OF A LARGE
PUBLIC COMPANY LI LIKE QIAGEN,
THEIR SHAREHOLDERS ALMOST ALWAYS
WANT A FINANCIAL RETURN.
HOWEVER, THERE ARE OTHER
FINANCING MODELS I WOULD LIKE TO
SHARE.
ONE OF WHICH, 20/20 I HAVE TO
SAY WAS A PIONEER IN AND HAVE
DONE WELL IN WHICH IS CALLED
PUBLIC EQUITY CROWD FUNDING
WHICH BECAME LEGAL ABOUT A
DECADE AGO OR SO, REG -- WE WERE
AN EARLY SUCCESS IN DOING THAT,
WE ACTUALLY RAISED OVER
10 MILLION IN EQUITY CROWD
FUNDING.
THE CHALLENGE OF THIS WILL IS
THAT INVESTORS INVEST -- THEY
CERTAINLY WANT A FINANCIAL
RETURN, BUT IT'S NOT NECESSARILY
THEIR ONLY MOTIVATION.
EQUITY CROWD FUNDING -- OFTEN
PEOPLE WILL INVEST IN A REGION
OR THEIR OWN CITY FOR ECONOMIC
DEVELOPMENT.
THEY WILL OFTEN INVEST IN A
DISEASE THAT THEY CARE ABOUT.
IT COULD BE SOMETHING IMPACTING
THEIR FAMILY, IT COULD BE SIMPLY
FOR PHILANTHROPIC REASONS.
SO THERE ARE MODELS,
PARTICULARLY FOR SMALL
COMPANIES.
I THINK DANIEL MENTIONED, IF I'M
NOT MISTAKEN, DON'T JUST THINK
ABOUT THE ABBOTTS AND ROCHE AND
THE SIEMENS AND QIAGEN, NO
DISRESPECT TO RAY, BUT THERE'S
AN ENTIRE ECOSYSTEM, AND THERE'S
NOTHING WRONG WITH A COMPANY
SAYING OUR MISSION IS TO ATTACK
DISEASE X IN COUNTRY Y.
BE VERY CLEAR ABOUT IT, AND
HOPEFULLY YOU'LL HAVE ENOUGH
SHAREHOLDERS, ENOUGH INVESTORS,
AND YOU COUPLE THAT WITH GRANTS
FROM GATES FOUNDATION, SBIR AND
SO ON AND SO FORTH, YOU CAN
CREATE A VIABLE BUSINESS.
IT MAY BE A SMALL BUSINESS, IT'S
NOT GOING TO BE A BILLION DOLLAR
COMPANY, IT PROBABLY WON'T WIND
UP ON THE NEW YORK STOCK
EXCHANGE, BUT IT'S SERVING ITS
MISSION.
AND SO EQUITY CROWD FUND
SOMETHING SOMETHING THAT'S A
VERY IMPORTANT TOOL THAT I THINK
CAN ADVANCE A LOT OF THESE
GOALS.
>> TO YOUR POINT, I THINK WHAT
WE'RE SEEING IN RECENT YEARS IS
AN INCREASE IN GLOBAL
STEWARDSHIP, CERTAINLY THE ESG
MOMOVEMENT IS MOVING INTO THE
PUBLIC MARKETS NOW WHERE SCC IS
LOOKING AT VARIOUS
CERTIFICATIONS FOR COMPANIES AND
ARE DOING ACTIVITIES IN THIS
PLACE, AND THE FACT THAT, YOU
KNOW, THERE IS I THINK AN
INCREASING RATE IN GLOBAL
STEWARDSHIP IN GENERAL.
A RECOGNITION THAT WE DON'T --
IN THE UNITED STATES AND WE HAVE
NOTHING TO DO WITH WHAT'S GOING
ON AROUND US.
SO I THINK WE'RE SEEING AN
AWARENESS.
CERTAINLY FROM QIAGEN IN OUR
HISTORY, IT COMES BACK TO GLOBAL
STEWARDNESS.
I'VE GIVEN YOU SOME HIGHLIGHTS.
WE ACTUALLY HAVE DIFFERENT
PRODUCTS BASED ON -- FROM THE
SAME INITIAL INVESTMENT THAT THE
MANIFESTATION OF THE PRODUCT,
HOW IT ACTUALLY GETS IT, AND
ALSO THINGS LIKE THE FALSE
POSITIVE, FALSE NEGATIVE RATIOS,
THE THRESHOLDS THAT ARE USEFUL
FOR A PARTICULAR PURPOSE CAN
VARY ACCORDINGLY.
BUT QIAGEN HAS EVOLVED INTO A
LATE STAGE DEVELOPMENT COMPANY.
WE REALLY THRIVE ON WORKING WITH
THE SMALLER COMPANIES AND
STARTUP COMPANIES, AND FROM THIS
SIDE, WE HAVE A TOOLS
ORGANIZATION AS WELL AS THE
DIAGNOSTIC.
WE'RE FAMILIAR WITH THE ENTIRE
SPECTRUM ACROSS THERE, AND SO
YOU CAN GET A LOT -- THERE'S A
LOT OF EXPERTISE AVAILABLE IN
WORKING WITH IT, BUT WE
ABSOLUTELY ARE ONLY ONE PART OF
IT, AND ONE APROA. T APPROACH.
>> RACHEL, DO YOU HAVE A COMMENT
YOU'D LIKE TO MAKE?
>> I WAS GOING TO SAY SOMEBODY
WITH THEIR BOOTS ON THE GROUND
AS AN EARLY STAGE FOUNDER AND
EARLY STAGE COMPANY, I HAVE SEEN
A LOT OF -- WITH A GLOBAL FOCUS,
SO IT'S NOT JUST AN IMPACT IN
THE UNITED STATES BUT WHAT'S
OUR -- WHAT IS OUR
COMMERCIALIZATION PLAN IN THE EU
IN SOUTH AMERICA AND PLACES OF
THAT, SO THERE REALLY AND TRULY
ARE IMPACT, FOR EXAMPLE, WITH
FATTY LIVER DISEASE, BUT THE
BURDEN OF DISEASE HASN'T BEEN
ENTIRELY REALIZED DUE TO THE
LACK OF FOCUS, ATTENTION,
EFFECTIVE DIAGNOSTIC TOOLS, SO I
SEE THAT A LOT FROM EARLY STAGE
VCs, SOME OF THE LARGER VCs
AS WELL FOCUSED ON THE SEED
SERIES A COMPANY, SO REALLY
THAT'S PART OF THE DISCUSSION
AND THE STRATEGY FOR A LOT OF
THE COMPANIES RIGHT NOW, WHAT IS
OUR PLAN OUTSIDE OF THE UNITED
STATES AS WELL, BECAUSE I THINK
IT'S LEADING A LOT OF -- LEAVING
A LOT OF OPPORTUNITY ON THE
TABLE TO ONLY FOCUS IN THE
UNITED STATES.
TOM, YOU BROUGHT UP A GREAT
POINT EARLIER WHERE YOU MENTION
THAT WE THINK OF FATTY LIVER
DISEASE AS A WESTERNIZED DIET,
AND TO AN EXTENT, IT IS, BUT
THAT'S NOT THE ONLY ETIOLOGY.
I THINK WE'VE BEEN -- AS I THINK
WE'VE BEEN LED TO BELIEVE.
SO WHAT ELSE IS FATTY LIVER
DISEASE, WHAT IS THE INCIDENCE
AND PREVALENCE AND HOW IS THAT
CHANGING OVER TIME AND WHY.
SO I THINK THAT THESE QUESTIONS
ARE YET TO BE ANSWERED AND
THERE'S A LOT TO IDENTIFY THERE.
>> I'M GOING TO GIVE RACHEL THE
LAST WORD.
WE WANT TO THANK ALL THE
PANELISTS FOR A TRULY GREAT
SESSION ON A VERY IMPORTANT
TECHNICAL APPROACH, IMPORTANT
GLOBAL HEALTH CONCERNS.
SO I JUST WANT TO REMIND THE
AUDIENCE BEFORE I END THIS ZOOM
SESSION TO PLEASE GO TO THE
CONCLUDING REMARKS BY NINA
SCHOR, ASSOCIATE DIRECTOR OF
NIH, FOR INTRAMURAL RESEARCH,
AND THANK YOU AGAIN TO THE
PANEL, AND HAVE A GOOD REST OF
YOUR DAY.
>> THANK YOU.
>> HELLO, AND GOOD AFTERNOON
FROM BETHESDA, MARYLAND.
WELCOME AND THANK YOU FOR
JOINING THE BIOMARKERS AND NOVEL
OUT COME PANEL.
WE HAVE AN EXCELLENT LINE OF
PANELISTS FROM BOTH THE NIH AND
INDUSTRY.
MI AM THE MODERATOR OF THIS PANL
DISCUSSION.
I'M A RHEUMATOLOGIST BY TRAINING
AND HEAD OF THE LUPUS CLINICAL
TRIALS UNIT, WHICH IS PART OF
THE NATIONAL INSTITUTES OF
ARTHRITIS, MUSCULOSKELETAL AND
SKIN DISEASES OF THE INTRAMURAL
RESEARCH PROGRAM OF THE NIH AND
HERE IN BETHESDA, MARYLAND.
I WILL BEGIN BY INTRODUCING ALL
OF THE PANELISTS FOLLOWED BY A
BRIEF PRESENTATION BY EACH OF
THEM.
PLEASE POST YOUR QUESTIONS IN
THE LIVE INTERACTION CHAT DURING
OR AFTER EACH SESSION.
IF YOUR QUESTION IS DIRECTED TO
A SPECIFIC PANELIST, PLEASE
MENTION THEIR NAME IN YOUR
QUESTION.
WE WILL RESPOND TO YOUR
QUESTIONS AT THE END AFTER ALL
PRESENTATIONS BY OUR PANELISTS
ARE DONE.
TH -- WHO WILL SOON BE STARTING
HIS CAREER AS A MEDICAL STUDENT,
SO THANK YOU, AMID, FOR
MODERATING.
SO I WILL BEGIN BY INTRODUCING
THE PANELISTS AND THEN I WILL --
THEN THEY WILL START THEIR
PRESENTATIONS.
AND THEN AFTER THAT, WE WILL DO
Q & A.
SO THE FIRST PANELIST IS RICHARD
SIEGAL, UNIVERSITY OF
PENNSYLVANIA SCHOOL OF MED
SIRNTION AND WORKED FOR 20 YEARS
AT THE NATIONAL INSTITUTES OF
HEALTH INTRAMURAL RESEARCH
PROGRAM IN BETHESDA, MARYLAND,
WHERE HE WAS CHIEF OF THE
AUTOIMMUNITY BRANCH AND THE
CLINICAL DIRECTOR OF NIAMS.
BASIC AND TRANSLATIONAL RESEARCH
IN CYTOKINE BIOLOGY, FOCUSED ON
TNF SUPER FAMILY AND RECEPTORS.
HE JOINED NOVARTIS IN 2018 AS
THE GLOBAL HEAD OF TRANSLATIONAL
MEDICINE FOR IMMUNOLOGY.
AFTER A LONG CAREER IN ACADEMY
AND RESEARCH.
AS THE HEAD OF THE
TRANSCRIPTIONAL MEDICINE FOR
IMMUNOLOGY, DR. SIEGEL HAS
OVERSEEN THE TRANSITION OF NEW
PLEAK ALREADY ENTITIES IN THE
LAB TO CREATE A BROAD SPECTRUM
OF AUTOIMMUNE CONDITIONS.
IN SEPTEMBER OF 2023, HE WAS
APPOINTED IP I YOU A KNOLL
RESEARCH DISEASE AREA HEAD AND
IS LOOKING FORWARD TO CONTINUING
HIS COMMITMENT IN BRIDGING THE
GAP BETWEEN LAB AND CLINICAL
RESEARCH AND DISCOVERING NEW
TREATMENTS TO IMPROVE THE LIVES
OF PATIENTS WITH AUTOIMMUNE AND
INFLAMMATORY DISEASES.
OUR SECOND PANEL IS SEAN ANJAN
ARALI -- OFAPPLIED PRECISION OMA
LASKER CLINICAL RESEARCH TENURE
TRACK INVESTIGATOR, NIH
DISTINGUISHED SCHOLAR.
HE HAS A JOINT APPOINTMENT AND
IS AN ASSOCIATE PROFESSOR OF
MEDICINE AT JOHNS HOPKINS SCHOOL
OF MEDICINE.
HIS RESEARCH MISSION IS TO
IMPROVE LUNG TRANSPLANT SURVIVAL
BY DEVELOPING BETTER DIAGNOSTIC
AND THERAPIES OF TRANSPLANT
REJECTION.
HIS LAB HAS SHOWN THAT A NOVEL
BLOOD TEST -- DNA RELIABLY
IDENTIFIES ORGANS AFFECTED BY
DISEASE PROVIDING A WHOLE BODY
MOLECULAR INJURY SCAN AND
IDENTIFIES HIGH RISK PATIENTS
WHO COULD BENEFIT FROM TAILORED
STRATEGY TO PREVENT EARLY DEATH.
HE ESTABLISHED A MULTICENTER
CONSORTIUM AND IS DIRECTOR OF
THE GENOMIC RESEARCH ALLIANCE
FOR TRANSPLANT OR GRAFT, A
HIGHLY COLLABORATIVE CONSORTIUM
WITH RESEARCH INFRASTRUCTURE AND
A LARGE AND DIVERSE PATIENT
COHORT TO TEST NOVEL THERAPIES
AND DIAGNOSTIC.
THE FIRST INTERVENTION CLINICAL
TRIAL IS PLANNED TO START IN
2024, AND -- EARLY DETECTION AND
TREATMENT OF REJECTION GUIDED
BY -- DNA IMPROVE NON-TRANSPLANT
OUTCOMES.
OUR THIRD PANELIST IS MOHAN
PURUSHOTHAMAN, PROGENTEC
DIAGNOSTICS, ACTIVELY INVOLVED
IN EXPLORING NEW TECHNOLOGIES IN
THE DIAGNOSTICS AND THIER PEW
TICK AREA.
HE HOLDS A PH.D. FROM THE JOHNS
HOPKINS UNIVERSITY WITH A FOCUS
IN PHARMACEUTICAL PRICING, AND
PRIOR TO OBTAINING HIS PH.D., HE
WAS A RESEARCH FELLOW AT
HARVARD.
DR. PURUSHOTHAMA NHAS A STRONG
RECORD IN THERAPEUTIC AND
DIAGNOSTIC TRACTS.
HE HAS SEVERAL YEARS OF
EXPERIENCE IN THE PHARMA
INDUSTRY FOLLOWED BY STRATEGIC
ADVISER SO VARIOUS
PHARMACEUTICAL COMPANIES
WORLDWIDE, HE SPENT ABOUT FIVE
YEARS AT ROCHE AND SPEARHEADED
FORMULATION OF LIFECYCLE PRICING
STRATEGIES FOR A LARGE NUMBER OF
PRODUCTS.
AND THEN HE HAS BUILT A
SUCCESSFUL PRACTICE AT NET
MARGIN, WHICH EVENTUALLY WAS
ACQUIRED BY ALLIANCE LIFE
SCIENCES.
AND THEN HE WAS THERE FOR GLOBAL
PRACTICE LEAD FOR PRICE AND
MARKETING UNTIL 2014, AND IN
THESE CHALLENGING ASSIGNMENTS,
HE GUIDED THE DEVELOPMENT OF
STRATEGIES FOR A NUMBER OF
PRODUCTS ACROSS MULTIPLE
THERAPEUTIC AREAS AND GLOBAL
MARKETS.
AND HE HAS BEEN AN ENTREPRENEUR
RESPONSIBLE FOR GIVING SHAPE TO
MULTIPLE BUSINESS CONCEPTS AT
THE CORE OF NEW BUSINESS
VENTURES AND HE HAS DESIGN AND
DEVELOPED AN ENTERPRISE SOFTWARE
THAT HAS NOW BECOME THE LEADING
PRODUCT USED BY A LARGE NUMBER
OF MAJOR PHARMA COMPANIES.
OUR FOURTH PANELIST IS PETER
BIRBILO, STAFF SCIENTIST IN THE
LAB OF SENSORY BIOLOGY, NATIONAL
INSTITUTES OF DENTAL AND
CRANIOFACIAL RESEARCH AT NIDCR
AT THE NIH.
HE RECEIVED HIS PH.D. IN
PHARMACOLOGY AND TOXICOLOGY FROM
THE UNIVERSITY OF RHODE ISLAND.
HIS RESEARCH IS DIRECTED AT
GENERATING HIGH DEFINITION
ANTIBODY PROFILES IN CANCER AND
INFECTIONS AND AUTOIMMUNE
DISEASES.
WHICH COULD PROVIDE
COMPREHENSIVE AND INEXPENSIVE
CLINICAL TOOLS FOR DISEASE
PREDICTION, DIAGNOSIS, AND
MONITORING OF TREATMENT FOR A
SPECTRUM OF HUMAN DISEASES.
HIS WORK ON THE LUCIFERASE
SYSTEMS THAT USES LIGHT EMITTING
LUCIFERASE FUSION PROTEIN AND
ASSAY FORMATS TO DETECT ROBUST
ANTIBODY MARKERS.
AND THIS IS CLINICALLY
RELEVANT -- THIS CLINICALLY
RELEVANT NOVEL BIOMARKER HAS
INDICATION FOR USE IN A VARIETY
OF AUTOIMMUNE CONDITIONS SUCH AS
SJOGREN'S DISEASE, SCLERODERMA
AND -- NEPHROPATHY.
HE DEVELOPED A SIMPLE AND ROBUST
IMMUNOCAPTURE METHOD BASED ON
LUCIFERASE FUSION PROTEINS
COUPLED WITH NEW MAGNETS FOR THE
CLINICAL MEASUREMENT OF ANTIBODY
LEVELS THAT CAN BE USED FOR THE
ULTRA RAPID DIAGNOSIS, LESS THAN
ONE MINUTE OF PATIENTS WITH
SJOGREN'S DISEASE, HPV
ASSOCIATED ADENOCARCINOMA AND
MANY OTHER SUCH DISEASE
ENTITIES.
SO THANK YOU, PETER.
NOW OUR LAST BUT NOT LEAST
PANELIST IS DR. CHRIS LEPTAK,
HIS GRADUATE WORK INCLUDED AN MD
AND PH.D. IN MYOBIOLOGY -- AFTEE
DID HIS RESIDENCY TRAINING AND
BRIGHAM AND WOMEN'S HOSPITAL AND
MASS GENERAL HOSPITAL.
HE JOINED FDA IN THE GASTROENT
ROLLING DIVISION.
PRIMARY FOCUS ON -- AND
BIOLOGICAL PRODUCT DEVELOP M.
AFTER JOINING THE OFFICE OF NEW
DRUG GUIDANCE AND POLICY TEAM,
HE BECAME OND'S FIRST BIOMARKER
AND COMPANION DIAGNOSTIC LEAD,
RESPONSIBLE FOR DEVELOPING
GUIDANCE AND EVIDENCE
REQUIREMENTS TO SUPPORT
REGULATORY ACCEPTANCE.
HE SERVED AS CHAIR OF --
COMMITTEE, GREU THE GROUP OF SER
STAFF FOR NOVEL SURROGATE END
POINTS AND ACCEPTANCE OF DDT
QUALIFICATION SUBMISSIONS.
FOUNDED AND CHAIRED AN FDA WIDE
BIOMARKER WORKING GROUP AND
AFTER 14 YEARS OF WORKING AT
FDA, HE JOINED GREENLEAF IN 2021
AS EXECUTIVE VICE PRESIDENT OF
DRUG AND BIOLOGICAL PRODUCTS.
HE SPECIALIZES IN REGULATORY USE
OF NOVEL CLINICAL END POINTS,
INCLUDING -- FOR BOTH
TRADITIONAL AND ACCELERATED
MARKETING APPROVAL AND
SCIENTIFIC ADVANCE, ADVICE AND
TECHNICAL DIRECTION ON CRITICAL
ASPECT OF DRUG DEVELOPMENT.
SO AS YOU CAN SEE, WE HAVE A
EXCELLENT LINEUP OF PANELISTS
AND WE ARE ALL LOOKING FORWARD
TO HEAR FROM THEM AND SEE HOW WE
CAN LEARN FROM THEM IN THIS
FIRST EVER NIH INDUSTRY SEMINAR.
SO THANK YOU TO ALL OF THE
PANELISTS, AND THEN I WOULD
REQUEST RICHARD TO PLEASE TAKE
IT AWAY.
THANK YOU.
>> THANK YOU.
CAN YOU ALL SEE MY SCREEN?
>> YES.
>> GREAT.
SO REALLY, THANK YOU, VERY HAPPY
TO BE HERE.
AS SARFARAZ SAID, I SPENT 20
YEARS AS A LAB INVESTIGATOR AND
ALSO AS CLINICAL DIRECTOR SO I'M
REALLY FAMILIAR WITH THE LAB AND
CLINICAL PROGRAMS AT NIH AND
REALLY HAPPY TO REFLECT ON BOTH
SOME OF THE WAYS THAT WE NOW IN
MY NEW POSITION AT NOVARTIS
LARGE PHARMA COMPANY WITH A VERY
LARGE RESEARCH GROUP INTERACT
WITH BOTH EXTERNAL PARTNERS AND
NIH IN PARTICULAR, AND I'LL KIND
OF GIVE TWO CASE STUDIES OF
PARTLY ONE FROM THE WORK I DID
AT NIH, AND HOW WE TRIED TO
DEVELOP A NOVEL THERAPEUTIC AND
THEN ALSO A VERY SUCCESSFUL CASE
WHERE NOVARTIS DEVELOPED A
THERAPEUTIC WITH THE NIH
CLINICAL CENTER AS THE MAIN
CLINICAL SITE.
SO I THINK THE WAY I'VE COME TO
SEE THAT THE INTERFACE BETWEEN
INTERNAL/EXTERNAL IS REALLY
AROUND THE CYCLE OF DISCOVERY.
SO WE THINK OF DRUG DEVELOPMENT
AS A PIPELINE BUT IT REALLY MUCH
MORE OF A CYCLE WHERE TARGETS
ARE IDENTIFIED, BIOMARCS ARE BIE
DISCOVERED AND DRUG CANDIDATES
ARE ADVANCED IN PRE-CLINICAL
TESTING AND CLINICAL TRIALS.
IMPORTANTLY TISSUE SAMPLES ARE
COLLECTED IN THOSE TRIALS, WHICH
CAN BE A VERY IMPORTANT PART OF
GOING BACK INTO HUMAN TISSUE AND
DATA ANALYSIS, BOTH
INTERVENTIONAL TRIALS AND LARGE
CONSORTIA OF NON-INTERVENTIONAL
TRIALS, AND ALL THOSE DIFFERENT
PHASES CAN BE MARKED BY INTERNAL
AND EXTERNAL COLLABORATION.
SO BOTH COLLABORATIONS WITH
SINGLE LABS AND INSTITUTIONS TO
REBLIND THAT EVERY SINGLE
CLINICAL TRIAL IS A
COLLABORATION, THERE'S NO KNOW
NOVARTIS CLINIC, MERCK CLINIC.
EVERYTHING IS DONE EXTERNALLY
WITH UNIVERSITIES AND THE NIH
CLINICAL CENTER AND THE CLINIC.
WE ALSO PARTICIPATE, OUR LARGER
PHARMA COMPANIES PARTICIPATE IN
PUBLIC-PRIVATE NETWORKS.
IN THE U.S., THE ADVANCING
MEDICINES PARTNERSHIP IS REALLY
THE PREMIERE ONE OVER THE LAST
10 YEARS NOW, THEY'RE ABOUT TO
HAVE A TENTH ANNIVERSARY.
AND THEN ALSO IN EUROPE, THERE'S
A VERY STRONG ORGANIZATION
SPONSORED BY THE EU, INNOVATIVE
MEDICINE INITIATIVES, NOW CALLED
INNOVATIVE HEALTH INITIATIVES
THAT ARE ALSO PUBLIC-PRIVATE
PARTNERSHIPS.
IN ADDITION, AS HAS BEEN DONE
OFTEN AT NIH, SPONSORED TRIALS,
INVESTIGATOR INITIATED TRIALS
CAN HAVE ADDITIONAL RESEARCH
THAT CAN GO BACK INTO THE
PIPELINE.
COLLABORATIONS FROM THE PHARMA
POINT OF VIEW COME IN MANY
TYPES, AND IT'S IMPORTANT TO
REMEMBER THAT UNIVERSITIES AND
NIH ARE JUST ONE TYPE, THROUGH
CRADAs, MTAs, CTAs AND
NOVARTIS DOES A LOT OF THAT ALL
OVER THE WORLD.
THERE'S ALSO THE PUBLIC-PRIVATE
PARTNERSHIPS THAT I MENTIONED,
MEETINGS.
ONE IMPORTANT THING TO MENTION
THAT HAS COME UP AND WAS SAID IN
SOME OF THE TALKS EARLIER, IT IS
MUCH EASIER, THERE'S A
COMPLETELY DIFFERENT PATHWAY TO
PARTNER WITH A SMALL BIOTECH,
WHICH IS I THINK THE BIGGEST
DISADVANTAGE OF NIH, NOT BEING
ABLE TO EASILY SPIN OFF FOR
BIOTECH, IT JUST A STANDARD
METHOD OF OPERATION OF MANY
ACADEMIC LABS.
SO ONCE THERE'S A SMALL BIOTECH,
NO MATTER HOW SMALL, THAT GOES
TO PARTNERING, AND THERE'S A
WHOLE ARMY OF PEOPLE THAT WORK
AT EVERY PHARMA COMPANIES THAT
ARE SCANNING THE WORLD FOR
POTENTIAL PARTNERING.
AND SO THE ACADEMIC PARTNERSHIPS
HAVE TO BE MUCH MORE SPEARHEADED
BY THE SCIENTISTS, THE
SCIENTIST-SCIENTIST INTERACTIONS
BUT THEY ALSO CAN BE VERY
PRODUCTIVE.
PHARMA COMPANIES ALSO SPONSOR
THROUGH MOST PHARMA COMPANIES
HAVE VENTURE CAPITAL ARMS THAT
SPONSOR WITHOUT OBLIGATION TO
DEVELOP EVEN EARLIER STARTUPS
AND THERE'S ALSO INCUBATORS OR
NETWORKING.
SO THE FIRST CASE STUDY I WANT
TO TALK ABOUT IS SOMETHING CLOSE
TO ACTIVITIES THAT I DID FOR A
LONG TIME AT NIH.
I WAS STUDYING IN TNF FAMILY
BIOLOGY AND WE MADE THE
OBSERVATION ALONG WITH A NUMBER
OF OTHER COLLEAGUES FROM NIH
THAT ONE OF THOSE FAMILY
MEMBERS, TL1A WHEN OVEREXPRESSED
CAUSED A INTESTINAL INFLAMMATION
WITH SOME SIMILARITIES TO
CROHN'S DISEASE AND UC, AND THIS
SAME CYTOKINE IS ALSO A MAJOR
GENETIC RISK FOR THE DEVELOPMENT
OF CROHN'S AND ULCERATIVE
COLIGHT.
SO THAT WAS BACK IN 2010.
SO THIS IS KIND OF A TYPICAL
THING.
I WAS A JUNIOR INVESTIGATOR AT
THAT TIME, AND WE MADE
ANTIBODIES AGAINST THE HUMAN
CYTOKINE, FILED AN INVENTION
REPORT AS WE'RE ENCOURAGED TO
DO, WHICH WAS GRANTED, WE ALSO
CHARACTERIZED THE SNP AND THE
FUNCTIONAL IMPLICATIONS OF THE
PROMOTOR SNP THAT'S LINKED TO
SUSCEPTIBILITY.
I WENT AROUND TO MANY COMPANIES
AND DID -- PARTNERSHIPS.
THIS IS WHERE I JUST RECOGNIZED
JUST MAKING A MONOCLONAL
ANTIBODY WITH A PA NENT ON IT IS
NOT SUS A VALUABLE COMMODITY FOR
BIOTECH OR PHARMA BECAUSE IT'S
SO EASY TO MAKE MONOCLONAL
ANTIBODIES.
NEVERTHELESS, AS AN NIH
INVESTIGATOR, THERE'S A LICENSE
TO A STARTUP THAT AS FAR AS I
KNOW HAS NOT DEVELOPED THE
ANTIBODY, BUT I THINK THAT WAS
SORT OF OUR EXPERIENCE AND ONE
ASPECT IN PARTNERING.
BUT I JUST WANT TO CONTRAST THAT
TO WHAT HAPPENED AT A VERY
COMMERCIALLY ORIENTED ACADEMIC
SETTING, CEDARS-SINAI, WHERE
ANOTHER INVESTIGATOR, WHO WAS A
GASTROENTEROLOGIST, FOUND A
SIMILAR OBSERVATION IN MICE BUT
THEN AS HAPPENS IN ACADEMIA, THE
UNIVERSITY CO-SPONSORED THE
STARTUP, THE STARTUP BECAME A
PUBLIC COMPANY, DEVELOPED THE
ANTITHERAPEUTIC ANTIBODY AND
IMPORTANTLY FOR THIS
CONVERSATION, DEVELOPED A
COMPLEMENTARY DIAGNOSTIC BASED
ON THOSE SNPs THAT WE HAD ALSO
WORKED ON, AND THEN VERY
EXCITING FOR THE FIELD, AND I
VIEW THIS AS GREAT SUCCESS OF
ALL OF OUR WORK IN THIS AREA, A
CLINICAL TRIAL DEMONSTRATED THAT
THE ANTIBODY WAS EFFECTIVE AND
ALSO THE BIOMARKER PREDICTED
SIGNIFICANT ENRICHMENT OF
REMISSION AND THEN THIS COMPANY
WAS ACQUIRED BY MERCK FOR
$10.8 BILLION, AND THE
SPONSOR -- THIS IS THE POTENTIAL
THAT NIH RARELY EXPERIENCES, THE
LEADING INVESTOR AT THE
UNIVERSITY EXPERIENCED A VERY
LARGE CAPITAL GAIN FROM THEIR
INVESTMENT.
BUT I THINK THAT ILLUSTRATES
SOME OF THE ADVANTAGES AND
PITFALLS OF THE NIH IRP AS A
PLACE, THERE'S BEEN MANY MORE
SUCCESSFUL EFFORTS THAN THIS
ONE, BUT I THINK IT DOES
ILLUSTRATE SOME OF THE ISSUES.
THE SECOND ONE, IT'S A VERY
DIFFERENT STORY SINCE THIS WAS
PN3 KINASE DELTA, AN ENZYME
DOWNSTREAM OF B CELERY SPEP TORE
AND OTHER SIGNALING MOLECULES,
AND IT WAS REALIZED IN THE EARLY
TWO THOUSANDS THAT THIS COULD BE
A GOOD DRUG TARGET, SO THIS
STORY BEGAN THE OPPOSITE WAY, SO
IN 2010, AT MY GROUP, BEFORE MY
TIME IN NOVARTIS, THIS WAS
IDENTIFIED AS A POTENTIAL TARGET
TO WHERE MULTIPLE DIFFERENT
AUTOIMMUNE DISEASES, AND IT WAS
A -- A CLINICAL CANDIDATE WAS
MADE, IT WAS A FIRST IN HUMAN
AND REALLY WITH NO INTENTION OF
GOING INTO A GENETIC DISEASE
TARGET, BUT THEN IN 2013, ALMOST
EXACTLY 10 YEARS AGO, MIKE
LEONARDO AND NIAID AND OTHER
INVESTIGATORS IN THE UK
DISCOVERED A GENETIC SYNDROME
CAUSED AN IMMUNODYSREGULATION
SYNDROME CAUSED BY GAIN OF
FUNCTION MUTATIONS IN THIS EXACT
ENZYME.
AND THAT LED TO VERY RAPID
COLLABORATION BECAUSE IT'S MUCH
MORE STRAIGHTFORWARD AND THIS IS
WHERE I THINK THE NIH AS AN
ENTITY THAT STUDIES A LOT OF
RARE DISEASES CAN REALLY SHINE.
IT WAS QUICKLY REALIZED THAT
THESE PATIENT, NIH WAS THE
LARGEST CENTER WITH NIAID AND
HIS PATIENTS, WOULD BE A GREAT
WAY TO TEST THE EFFICACY OF THIS
MOLECULE IN A SYNDROME THAT'S
CAUSED BY GAIN OF FUNCTION
ACTIVITY.
AND SO VERY QUICKLY, A TRIAL WAS
SET UP, AND YOU CAN SEE THE
TIMELINE, NOT TOO BAD, JUST
ABOUT A YEAR AND A HALF FROM
DISCOVERY PUBLICATION TO
CLINICAL TRIAL START, AND THEN A
YEAR LATER, THERE WAS A POSITIVE
PROOF OF CONCEPT, WHICH YOU CAN
ACHIEVE VERY QUICKLY IN A RARE
DISEASE.
UNFORTUNATELY, THE BIGGER
AMBITIONS FOR THIS MOLECULE TO
TREAT SJOGREN'S DISEASE AND
RHEUMATOID ARTHRITIS ARE NOT
REALIZED, THE TRIAL RESULTS WERE
LARGELY NEGATIVE AND THERE WERE
SOME INTERESTING ADVERSE EVENTS
WHICH HAPPENED -- PATIENTS,
BUT -- AND THIS IS WHERE I THINK
IT'S ANOTHER LESSON IN A RARE
DISEASE ONLY POPULATION, THIS
MAY NOT BE AN APPROPRIATE DRUG
TARGET FOR LARGE PHARMA, EVEN
THOUGH NOVARTIS HAD DONE A LOT
WITH TREATING RARE INFLAMMATORY
SYNDROMES WITH IL-1 INHIBITION
WAS DECIDED TO OUTLICENSE, BUT
THAT IS ALSO A PATHWAY THAT CAN
HAPPEN, SO THIS WAS MOLECULES
OUTLICENSED TO AN ORPHAN DRUG
COMPANY BUT OUR GROUP ACTUALLY
CONTINUED THE PIVOTAL TRIAL
WHICH WAS THEN STARTED AND
APPROVAL WAS GRANTED JUST LAST
YEAR.
I THINK SOME OF THE KEY FEATURES
THAT MADE THIS A REALLY
SUCCESSFUL PARTNERSHIP WERE THAT
NIAID AND MIKE AND OTHERS WERE
VERY OPEN TO PARTNERING, AND THE
TECH TRANSFER OFFICE WAS REALLY,
I THINK, GREAT AND EVEN IN
BENDING THE TYPE OF CLINICAL
TRIAL AGREEMENT WHICH IS NOT
FRIENDLY AND WE CAN TALK ABOUT
THAT IN THE Q & A, TO INDUSTRY
PARTNERSHIPS, BUT IT WORKED AND
MOST OF THE DATA, ABOUT HALF THE
PATIENTS IN THE PIVOTAL TRIAL
WERE AT NIH, AND THEN -- SO I
THINK IT'S A GREAT STORY.
VERY RARELY DO YOU GO 10 YEARS
FROM DISCOVERY OF A DISEASE TO
AN FDA-APPROVED THERAPY, BUT
THIS REALLY WAS A GREAT SUCCESS
IN THAT WAY.
SO JUST TO WRAP UP, I THINK I
WANTED TO SAY SOME POINTS AND TO
JUST KIND OF LEAVE FOR THE
DISCUSSION, BUT I THINK WHERE
THINGS CAN GO RIGHT AS WAS SEEN
THERE, AND I HEARD SOME GREAT
STORIES EARLIER IN THE DAY, AND
I THINK MANY OF YOU ARE AWARE,
THE PARTNER IN THE COMPANY NEEDS
TO HAVE THE SAME GOAL.
THAT HAS TO BE REALLY SPELLED
OUT, IT CAN'T JUST BE A KIND OF
VAGUE THING, IT HAS TO BE
SPELLED OUT AND ALSO THE DETAILS
OF IP PUBLICATION STRATEGY MUST
BE SPELLED OUT UP FRONT.
IF THE ACADEMIC PARTNER HAS IP
AT STAKE, WHICH WASN'T THE CASE
HERE, THAT CAN BE BETTER
ACCOMPLISHED POTENTIALLY WITH
BUSINESS DEVELOPMENT AS A
SPINOFF COMPANY AND THAT IS THE
PARTICULAR CHALLENGE OF NIH THAT
IS DIFFICULT TO DO IN THE
CURRENT FRAMEWORK.
IT ALSO REALLY NEEDS SCIENTIST
CHAMPIONS ON BOTH SIDES.
I'VE BEEN INVOLVED IN A NUMBER
OF BILATERAL CLAB WRAITIONS AND
BECAUSE THERE'S NO ARMY OF
PARTNERING BUSINESS PEOPLE TO
HELP, IT REALLY HAS TO BE DRIVEN
BY THE SCIENTISTS WORKING WITH
THE TECH -- OFFICE TO GET A
PARTNERSHIP SIGNED AND ALSO FOR
FOLLOW-UP OF THE RESULTS.
THERE IS THIS ISSUE AS WAS
DISCUSSED EARLIER IN THIS
MEETING, YOU SHOULD DEFINITELY
REACH OUT TO BIOTECH AND PHARMA
IF YOU WANT TO USE A DRUG FOR
AN -- BUT THAT CAN BE A PROBLEM,
ESPECIALLY DEPENDING ON THE
STAGE OF DEVELOPMENT, IF IT IN
SENSITIVE STAGES, TYPICALLY
PHASE THREE IS THE HARDEST AND
TYPICALLY UP TO EACH COMPANY,
EACH CIRCUMSTA CIRCUMSTANCE, ANE
IP CAN BE AN ISSUE AS ONE OF THE
NIAMS COLLABORATIONS WE WERE
INVOLVED WITH. HOWEVER,
PUBLICATIONS ARE NOT AN ISSUE.
ONCE YOU HAVE A TRIAL, FIRST OF
ALL, IT HAS TO BE PUBLIC, AND
EVERYBODY REALLY DOES WANT TO
PUBLISH THAT, WHETHER
DEVELOPMENT GOES ON OR NOT.
SO THAT'S NOT A LIMITATION.
IN A LIN C CLINICAL STATE YOUR .
WHERE PUBLICATIONS ARE LIMITED
IS IN THE CLINICAL PHASE.
-- DID SHARE THIS FEELING THAT
NIH IS JUST TOO TOUGH TO
COLLABORATE WITH, THE IRP, AND
THE TECH TRANSFER MODEL, THE
PAYMENT ISSUE OF HOW CRADAs
ARE FUNDED IS VERY DIFFERENT
THAN ANY OTHER PLACE IN THE
WORLD.
THAT IS MORE RESTRICTIVE.
THE BLOCK GRANT IS MUCH -- IS
UNUSUAL COMPARED TO A
PER-PATIENT FEES THAT ARE
STANDARD EVERY EVERYWHERE ELSE E
WORLD FOR CLINICAL
COLLABORATIONS BUT IT CAN BE
DONE.
IT HAPPENS WE HAVE A GREAT
COLLABORATION, OUR GROUP, WITH
BIBI -- WE'RE DOING ANKYLOSING
SPONDYLITIS WORK, AND AT A
CONSORTIUM LEVEL, THAT'S ALSO
POSSIBLE.
SO I THINK EVERYTHING IS
POSSIBLE BUT THERE ARE SPECIFIC
ISSUES WITHIN NIH THAT MAKE IT
MORE DIFFICULT THAT NEED TO BE
WORKED THROUGH.
SO OVERVIEW HOPEFULLY THAT WAS
HELPFUL AS GIVING SOME OF MY
EXPERIENCES AND I'LL PASS IT
BACK.
>> THANK YOU SO MUCH, RICHARD.
THAT WAS VERY INSIGHTFUL AND
YOUR UNIQUE PERSPECTIVE OF BOTH
INSIDE AND OUTSIDE.
SO WE ARE NOW GOING TO MOVE ON
TO OUR NEXT SPEAKER, BUT BEFORE
I DO THAT, I JUST WANTED TO
REMIND EVERYONE THAT THE LIVE
INTERACTION CHAT IS SORT OF A
TEAL BAR ACROSS YOUR SCREEN.
PLEASE POST YOUR QUESTIONS
THERE, EITHER FOR -- IN GENERAL
FOR ALL OF THE PANELISTS OR ANY
SPECIFIC QUESTIONS FOR RICHARD
OR ALL THE REST OF THE PANELISTS
WHO ARE COMING AFTER HIM, AND WE
WILL GET TO YOUR QUESTIONS AFTER
THAT.
WITH THAT, I WILL NOW ASK DR
DR. SEAN AGBOR TO GO AHEAD.
>> LET ME SEE IF I CAN GIVE YOU
A PERSPECTIVE FOR A TENURE TRACK
INVESTIGATOR WITHIN THE NIH,
DEVELOPING THINGS LIKE WHAT
WE'RE DOING IN THE LAB THAT
COULD BE BROUGHT TO PATIENTS AND
SOME OF THE CHALLENGES THAT
WE'RE FACING WITH THAT.
I'LL TALK A LITTLE BIT ABOUT
CELL FREE DNA FOR EARLY
DETECTION OF DISEASE, TREATMENT
EFFECT, OR TISSUE INJURY.
SO WHAT ARE CELL FREE DNA?
JUST AN OVERVIEW.
WHEN CELLS IN THE BODY DIE OR GO
THROUGH DIFFERENT PROCESSES,
THEY ARE RELEASED, THEIR
CONTENTS.
SOME OF THAT CONTENT END UP IN
YOUR SICK LAITION OR IN YOUR
BLOOD.
PART OF THAT CONTENT OF THE CELL
IS DNA, SO THAT CELL-FREE DNA,
THAT'S DNA THAT'S OUT OF A CELL,
CIRCULATING IN BLOOD, OR IT
COULD BE IN OTHER BIOLOGIC
FLUIDS.
IT IS REALLY QUITE ABUNDANT IN
BLOOD.
IN HEALTHY PATIENTS, IT CAN HAVE
UP TO $10 BILLION, WHICH SOURCE
OF BIOMOLECULES, SO WE STARTED
OUT TO SAY BIOMARKER.
AND WE'VE DEVELOPED SOME NOVEL
APPROACHES IN WHICH A VIAL OF
BLOOD, YOU CAN EXTRACT PLASMA
FROM THAT AND WITH THAT, YOU CAN
THEN TARGET TISSUE-SPECIFIC DNA
SIGNATURES LIKE EPIGENETIC
FINGERPRINTS THAT ARE PRESERVED
ON CELL-FREE DNA AS IT LEAVES
THE CELL, AND YOU CAN THEN TEASE
OUT WHICH TISSUES IN THE BODY
ARE UNDERGOING INJURY PROVIDING
A WHOLE BODY MOLECULAR INJURY
SCAN.
I'LL SHOW YOU A FEW EXAMPLES AND
THEN I'LL GO TO SOME STUDIES.
IMAGINE THAT THESE ARE TWO
PATIENTS -- NOT IMAGINE, THESE
ARE INDEED TWO PATIENTS WITH
COVID-19 WHO DIED.
IF YOU LOOK AT THESE PATIENTS,
THE CELL FREE DNA IS HIGH IN THE
EARLY TIME OF THEIR
HOSPITALIZATION, THE LEVELS ARE
HIGH, THE LEVELS DECREASE OVER
TIME AS THESE PATIENTS ARE
TREATED.
UNFORTUNATELY, BETWEEN THE 10
AND DAY 14, THESE PATIENTS GO
INTO A SECOND PHASE OF COVID
THAT WE CALL THE INFLAMMATORY
PHASE OF COVID.
EXPONENTIAL RISE IN THEIR DNA
UNTIL UNFORTUNATELY THESE
PATIENTS DIE.
WE PRESENTED DIFFERENT TISSUE
TYPES THAT'S BEEN INJURED IN
THESE PATIENTS OVER TIME.
COMPARE THAT THEN WITH THE
FOLLOWING TWO PATIENTS WITH
COVID-19 WHO IN THIS CASE
SURVIVED.
IF YOU LOOK AGAIN, AT THE TIME
OF ADMISSION, THEIR CELL-FREE
DNA IS HIGH BUT NOT AS HIGH AS
THE PATIENT WHO DIED.
THE TRENDS OF THEIR CELL FREE
DNA ALSO DIFFERS, AND THE TISSUE
TYPES PRODUCED IN THEIR
CELL-FREE DNA OVERTIME ALSO
DIFFERS FROM THE PATIENTS WHO
DIED.
SO USING THIS EXAMPLE OF
COVID-19, WE DEMONSTRATED THAT
WITH A VIAL OF BLOOD, YOU CAN
TEASE OUT A CERTAIN SET OF UP TO
42 DIFFERENT TISSUE TYPES,
WHETHER OR NOT THEY HAVE BEEN
INJURED AND IF SO, BY HOW MUCH,
AND WITH THAT INJURY, YOU SHOW
DIFFERENT TRENDS IN THE PATIENTS
WHO HAVE DIFFERENT OUTCOMES.
MORE IMPORTANTLY IS THE NEXT
SLIDE.
SO THIS ASSAY CAN PICK UP
DIFFERENT TISSUES.
THIS IS A GROUP OF RESEARCHERS,
PARTICULARLY FROM AROUND THE
WORLD, WHO HAVE HELPED TO BUILD
SOME OF THESE PLATFORMS,
INCLUDING OUR LAB AS WELL.
SO YOU CAN PICK UP INJURY FROM
DIFFERENT TISSUE TYPES USING
THIS.
NEXT POINT IS, YOU CAN PICK UP
INJURY SO MUCH MORE EARLY.
IF YOU IMAGINE THIS AS A LONG
TRANSPLANT COHORT HERE WHICH WE
STUDIED, AT TIME ZERO IS THE
TIME A PATIENT WITH LONG
TRANSPLANT DEVELOP REJECTION.
IF YOU LOOK AT CELL-FREE DNA AT
THAT TIME, THE LEVELS ARE HIGH.
BUT MORE IMPORTANTLY, TWO TO
FOUR MONTHS BEFORE THAT PATIENT
SHOWS ANY CLINICAL SIGNS OF
REJECTION, BEFORE THE BIOPSY OF
THAT PATIENT SHOWS SIGNS OF
REJECTION, THEY HAVE ELEVATIONS
IN CELL-FREE DNA, A TOOL FOR
EARLY DETECTION.
WE SHOWED THE SAME THING IN
HEART TRANSPLANTATION AS WELL.
AND WE'VE GONE FORTH TO SHOW THE
SAME PRINCIPLES IN DISEASES
BEYOND TRANSPLANTATION.
THIS IS SMALL SYSTEM
INFLAMMATORY SYNDROME IN
CHILDREN, WHICH IS AN
INFLAMMATORY SYNDROME THAT
CHILDREN GET AFTER THEY GET
COVID-19.
WE SHOWED THE SAME PRINCIPLE
THERE IN COVID-19 AS WELL.
IN TRANSPLANTS, IN
GRAFT-VERSUS-HOST DISEASE,
PULMONARY HYPERTENSION, AND
OTHER DISEASES AS WELL.
SO THE SECOND THING WE COULD
OFFER IN ADDITION TO THIS
BIOMARKER IS A -- PHENOTYPE
PATIENT COHORT.
WHAT WE HAVE IS A CONSORTIUM OF
CENTERS HERE IN THE DMV
MID-ATLANTIC REGION.
THIS IS AN NHLBI-SPONSORED
CONSORTIUM BETWEEN THE NHLBI AND
FIVE HOSPITALS WITHIN THIS AREA
THAT PERFORM HEART AND LUNG
TRANSPLANT.
WE HAVE A LARGE PHENOTYPE COHORT
FROM THIS AS WELL.
SO WITH THESE TWO, A BIOMARKER
AND THIS POPULATION, WE'VE BEEN
FORTUNATE TO HAVE SOME
PARTNERSHIPS WITH INDUSTRY.
THE FIRST WAS TRULY REMARKABLE
DURING COVID-19.
THIS IS AN EXAMPLE OF AN
INDUSTRY PARTNERSHIP WITH KDX
THAT WENT FROM BEGINNING TO
FINISH LINE VERY QUICKLY.
IN THIS STUDY WHICH WE'RE USING
CELL-FREE DNA TO MONITOR
PATIENTS INSTEAD OF BIOPSY,
WHICH IS THE GOLD STANDARD NOW,
THIS WAS ALSO WITHIN THE
COVID-19 PANDEMIC, AND THERE ARE
A LOT OF RULES WHERE THE NIH
TECH TRANSFER PEOPLE WORKED IN
MY VIEW REALLY SEAMLESSLY WITH
THE INDUSTRY PARTNERS TO REALLY
GET THIS TO WORK.
AND SO IT WAS A MULTICENTER
STUDY, FOUR CENTERS, AND WITHIN
ONLY 18 MONTHS, FROM THE
BEGINNING OF THE STUDY, THAT
PAPER WAS PUBLISHED, LOOKING AT
THE PUBLICATIONS THERE, AND THEY
STUDIED AND PROPOSED A
MONITORING PROTOCOL THAT HAS
BEEN ADOPTED BY MULTIPLE CENTERS
ACROSS THE U.S. AND CANADA.
SORE THE INDUSTRY PARTNERS
WORKED VERY QUICKLY, AND THEY
GET THE KIND OF RESOURCES THAT
WAS JUST AMAZING, SEAMLESSLY PUT
TOGETHER, TO BRING THIS TO
COMPLETION.
COMPARE THAT TO ANOTHER
PARTNERSHIP, THIS TIME WITH
DIFFERENT INDUSTRY, WE'RE TRYING
TO PROPOSE A RANDOMIZED CONTROL
TRIAL OF CELL-FREE DNA AGAINST
BIOPSY OR -- BIOPSY WHICH IS THE
CURRENT GOLD STANDARD TO LOOK
FOR TRANSPLANT REJECTION.
SO THAT STUDY DID NOT GO AS THE
PRIOR STUDY.
WE TOGETHER ARE WORKING WITH
INDUSTRY PARTNERS.
WE WROTE THE PROTOCOL WITH OUR
TECH TRANSFER ESTABLISHED SOME
CRADA OR SOME AGREEMENT WITH
INDUSTRY, THIS WAS SUPPOSED TO
BE -- I THINK A 25-CENTER STUDY
NATIONALLY AND IN CANADA.
WE CALLED A MEETING,
INVESTIGATORS FROM ALL THE
CENTERS THAT CAME TO THE
MEETING, A LOT OF ENTHUSIASM
BUILT IN THE FIELD.
WE HA HAD A PRELIMINARY MEETING
WITH THE FDA AND THEN
UNFORTUNATELY, THE COMPANY
PULLED THEIR FUNDS, AND THAT
STUDY DID NOT PROCEED TO
CONCLUSION.
SO THOSE ARE TWO EXAMPLES
THAT -- OUR INTERACTIONS WITH
INDUSTRY.
SO WHAT WE HAVE HERE, AND
ACTIVELY, I MEAN, I REALLY
APPRECIATE THE TALK TODAY FROM
OTHERS ABOUT THIS APPROACH TO
ACTIVELY SOUGHT OUT INDUSTRY,
HOPEFULLY WE CAN TALK TO TECH
TRANSFER AND EXPLORE THAT.
BECAUSE WHAT WE HAVE IS WE'RE
DEVELOPING BIOMARKERS THAT CAN
DO THINGS OR CAN BRING NEW LIGHT
INTO DIFFERENT DRUGS OR
DIFFERENT WAYS IN WHICH WE THINK
ABOUT DISEASE.
THESE BIOMARKER CELL FREE DARN S
ABLE TO PROVIDE A WHOLE
MOLECULAR INJURY SCAN.
NOW THE QUESTION IS, WHAT DO YOU
DO WITH THIS?
AS AN NIH LAB, TRYING TO DEVELOP
THESE METHODS THAT COULD COME
INTO PATIENTS VERY QUICKLY.
I THINK RELATIONSHIP WITH
INDUSTRIES WOULD BE CRITICAL IN
DOING THAT.
AND I WILL STOP HERE.
>> THANK YOU SO MUCH, DR. AGBOR,
FOR THAT VERY INTERESTING
PERSPECTIVE FROM THE INTRAMURAL
NIH PERSPECTIVE.
NOW WE'LL SWITCH BACK TO
INDUSTRY AND OUR NEXT SPEAKER IS
DR. PURUSHOTHAMAN.
PLEASE TAKE IT AWAY.
>> HELLO, EVERYONE.
THANK YOU AND GOOD AFTERNOON.
THANK YOU FOR BEING HERE FOR THE
PRESENTATION.
I HOPE EVERYONE CAN SEE THE
SCREEN.
SO LET ME START OFF, THANK YOU,
DR. HASNI AND NIH FOR ORGANIZING
THIS GREAT OPPORTUNITY.
EXCITED TO BE HERE.
SO I AM THE CEO OF PROGENTEC
DIAGNOSTICS.
SO A LITTLE BIT ABOUT PROGENTEC.
WE ARE A DIGITAL HEALTH COMPANY,
IN THE AUTOIMMUNE SPACE WHERE WE
ARE FOCUSED ON BRINGING TOGETHER
BIOLOGIC SIGNALS AS WELL AS
DIGITAL SIGNALS TOGETHER INTO AN
AI ENVIRONMENT AND COMBINING
THAT WITH VARIOUS INTERVENTIONS,
BOTH DIGITAL AS WELL AS VIRTUAL,
TO BRING ABOUT MEANINGFUL
DIFFERENCE TO PATIENTS.
OUR FIRST FORAY INTO THE SPACE
HAS BEEN IN LUPUS, WE'RE NOW
WORKING ON A FEW OTHER SIMILAR
CONDITIONS.
THE CHALLENGE HAS YOU CAN
IMAGINE IN THE AUTOIMMUNE WORLD
IS THAT MOST OF THE TREATMENT
PARTICULARLY FOR THE DISEASES WE
ARE TALKING ABOUT HERE, LUPUS,
YOU KNOW, THE TREEMENT AND
MANAGEMENT IS OFTEN VERY
REACTIVE.
SO OFTENTIMES, YOU KNOW, YOU
TREAT THESE PATIENTS ON
SYMPTOMATOLOGY, AND ALL OF THIS
LEADS TO POOR PATIENT OUTCOMES
AND POTENTIALLY ALSO QUITE A BIT
OF THE RESOURCES BEING USED UP
FOR SUBOPTIMAL OUT K OUTCOMES IE
PATIENTS.
SO OUR APPROACH HAS BEEN
SOMEWHAT UNIQUE AND WHAT WE TRY
TO DO HERE IS WE HAVE A
DATA-DRIVEN PLATFORM, WE BRING
TOGETHER PL -- WE USE SIGNALS TO
GIVE US THAT PREDICTIVE ABILITY
AND WE THEN USE DIGITAL AND
VIRTUAL INTERVENTIONS TO MAKE A
DIFFERENCE TO THESE PATIENTS.
ALL OF THIS COMES TOGETHER INTO
A PLATFORM THAT ALLOWS THE
PHYSICIAN TO KIND OF TAKE THIS
PATIENT THROUGH A MORE OF A
PROACTIVE CARE MANAGEMENT.
SO OUR INITIAL FORAY HAS BEEN
INTO LUPUS.
WE ARE ALSO WORKING ON MS AND A
FEW OTHER AUTOIMMUNE CONDITIONS.
NOW, TALKING ABOUT PARTNERSHIP
WITH NIH AS A SMALL COMPANY,
STARTUP COMPANY, WE HAVE BEEN
ENGAGED WITH NIH FOR QUITE SOME
TIME AND IT BEEN SOMEWHAT
CENTRAL TO OUR R & D EFFORTS IN
SOME WAY.
SO LOOKING AT MORE OF THE
EXTRAMURAL SIDE, WE HAVE BEEN,
YOU KNOW, VERY ACTIVELY INVOLVED
IN GETTING SBIR GRANT, ONE OF
OUR COMMERCIAL READINESS
PROGRAM, OUR GRANT IS CURRENTLY
BEING EVALUATED, NIH HAS BEEN
INSTRUMENTAL IN TAKING US TO
VARIOUS -- PARTICULAR TO THE BIO
CONFERENCE, ALLOWING US TO PITCH
TO INVESTORS WHO ALL OF THAT HAS
BEEN GOING ON.
BUT I THINK THE FOCUS HERE TODAY
IS ON THE INTRAMURAL SIDE, THE
COLLABORATION THAT WE HAVE BEEN
ABLE TO ESTABLISH WITH NIAMS.
SO THIS STARTED SOMETIME IN 2020
WITH DR. HASNI REACHING OUT TO
US AND BASED ON THAT, WE WERE
ABLE TO IDENTIFY AN OPPORTUNITY
AND REALLY WORK OUT THE DETAILS
FOR A COLLABORATIVE ARRANGEMENT,
AND SINCE THEN, WE HAVE
ESTABLISHED A CRADA AGREEMENT
LATE 2021, EARLY 2022, AND SINCE
THEN, WE HAVE BEEN CONTINUING
DISCUSSIONS IN VARIOUS ASPECTS,
EVERYTHING FROM AVAILABILITY OF
RESOURCES TO LOGISTICS AND A
NUMBER OF OTHER POTENTIAL ISSUES
BUT WE FEEL THAT THE PROJECT
THAT WE HAVE WORKED OUT WILL SEE
GOALS REALIZED BY THE END OF
THIS YEAR.
SO THE OVERALL STRUCTURE AND
FRAMEWORK WE AGREED TO WITH THE
GROUP ESSENTIALLY INVOLVED THE
COMPANY TAKING ON 100 LUPUS
PATIENTS FROM OUT OF THE NATURAL
HISTORY COHORT OF PATIENTS, AND
FOLLOWING THEM LONGITUDINALLY
OVER TIME AND DURING THIS TIME
COLLECTING BIOLOGIC SAMPLES SO
WE CAN LOOK AT BIOMARKERS OF
INTEREST TO US THAT WOULD
SUPPORT SOME OF THE TECHNOLOGIES
THAT WE HAVE DEVELOPED IN HOUSE.
IN ADDITION TO THAT, ALSO ON
ONBOARD THESE PATIENTS IN OUR
COMPREHENSIVE MANAGEMENT CARE
SOLUTION PROGRAM, UNDER THIS,
THESE PATIENTS ARE, YOU KNOW,
GIVEN SMALL DEVICES TO CAPTURE
PROs, SURVEYS, BIOMETRIC DANA
AND OTHER DATA COMPONENTS THAT
ARE PART OF THAT PROGRAM.
AND IN TERMS OF THE FRAMEWORK
THAT WAS AGREED ON TO PURSUE
THESE GOALS, THE NIH WAS
RESPONSIBLE UNDER THIS FRAMEWORK
TO IDENTIFY -- FROM OUT OF THE
COHORT INTO THE STUDY.
AND HELP
US COLLECT BIOLOGIC SAMPLES,
PATIENT D DATA, PATIENT-REPORTED
OUTCOMES AND OTHER DATA THAT IS
REQUIRED.
FROM OUR PERSPECTIVE, WE WERE
OBVIOUSLY GETTING THESE SAMPLES,
ANALYZING THEM AND COMING UP
WITH OUR PROPRIETARY TEST
INDICES THAT WERE PASSED --
THEY'RE TO BE PASSED BACK TO THE
PHYSICIAN, AND IN ADDITION TO
THAT, THE SOFTWARE SUPPORT
DEVICES, EVERYTHING ELSE THAT'S
REQUIRED TO ONBOARD THEM ONTO
OUR COMPREHENSIVE MANAGEMENT
CARE SOLUTION.
AND IT GOES WITHOUT SAYING ALL
OF THE DATA COLLECTION
AGGREGATION ANALYSIS OF DIGITAL
AND BIOMETRIC DATA, ALL OF THIS,
THESE ARE ALSO COMPONENTS OF
THIS VERY INNOVATIVE
COLLABORATIVE FRAMEWORK.
SO LOOKING AT SOME KEY TAKEAWAYS
AND SOME GENERAL OBSERVATIONS
HERE, NOW, OBVIOUSLY THE NATURAL
HISTORY COHORT, THE LUPUS PHASE
IS A UNIQUE COLLABORATION
OPPORTUNITY FOR ANYONE DOING
RESEARCH WORK IN LUPUS.
SO WE FOUND THAT TO BE AN
EXTREMELY VALUABLE, YOU KNOW,
ASSET, AND WANTED TO, YOU KNOW,
AGAIN, THE FACT THAT IT HAS THE
LONGITUDINAL NATURE OF THAT IN
THE AVAILABILITY OF WELL
CHARACTERIZED PATIENT DATA, ALL
OF THOSE ARE OF IMMENSE VALUE TO
ANYONE DOING WORK IN THIS SPACE.
I THINK WHAT WE REALLY
APPRECIATE HERE IS THE FACT THAT
THE SOLUTION THAT WE HAVE IS
SOMEWHAT A NOVEL AND ALSO IT'S
GOT SOME VERY UNIQUE PARAMETERS,
COMBINING DIGITAL AND BIOMARKER
SIGNALS SO PROVIDE DEEPER
INSIGHTS TO A PHYSICIAN MANAGING
THESE CONDITIONS, AND MAKING AN
IMPACT, YOU KNOW, WHEN YOU THINK
IN TERMS OF IMPLEMENTING
SOMETHING LIKE THIS, IT ALWAYS
POSES SOME CHALLENGES.
BUT WE WERE PARTICULARLY
IMPRESSED WITH NIH'S WILLINGNESS
TO ENTERTAIN THESE KINDS OF
APPROACHES AND REALLY SUPPORT US
AND PROVIDE THAT OPPORTUNITY SO
THAT WAS SOMETHING THAT WE
THOUGHT WAS VERY, VERY
ENCOURAGING FOR US AS A WELL.
IN TERMS OF SOME OF THE -- I
WON'T SAY CHALLENGES BUT THE
FACT THAT IT TAKES US LONGER TO
IMPLEMENT SOMETHING LIKE THIS,
OBVIOUSLY THE FACT THAT I
MENTIONED BEFORE THE NOVEL
APPROACHES, YOU KNOW, AND
OBVIOUSLY THAT REQUIRES -- THAT
POSES ITS OWN UNIQUE CHALLENGES,
REQUIRES DECISION-MAKING,
BECOMES -- IT INVOLVES MULTIPLE
AGENCIES AND ALL OF THAT, SO
THERE ARE SOME CHALLENGES THAT
COME UP FROM THAT.
THE OTHER AREA, AND I THINK THIS
HAS BEEN TALKED ABOUT BEFORE,
BUT AS A SMALL COMPANY, A
STARTUP, WE ARE ALWAYS FACING,
YOU KNOW, FUNDING AND OTHER
ISSUES AND IN MOST OF THESE
STUDIES, WE ARE REQUIRED TO DRAW
ON OUR OWN CAPITAL IN MOST
CASES, INVESTMENT CAPITAL.
SO THIS WAS SOME OF THE THINGS
THAT WE AS A COMPANY FACE.
I JUST WANT TO KIND OF EMPHASIZE
THAT AS A SMALL COMPANY, THIS
BECOMES FURTHER ENHANCED AS A
BIGGER ISSUE FOR US.
OTHER AREAS OF INTEREST, FROM
PROGENTEC'S PERSPECTIVE, WE HAVE
BEEN LOOKING AT TWO OTHER AREAS
WHERE WE HAVE BEEN DOING QUITE A
BIT OF WORK, AND THESE ARE FROM
OUR PERSPECTIVE MANAGING LUPUS
PATIENTS, THESE ARE MAJOR
CHALLENGES AND HUGE UNMET NEEDS
IN THIS SPACE.
SO THE FIRST IS EARLY
CLASSIFICATION OF LUPUS
PATIENTS.
AND WE CURRENTLY HAVE A STUDY
THAT'S GOING ON WITH A HUNDRED
PATIENT, BUT WE ARE OBVIOUSLY
LOOKING FOR OTHER WAYS TO WORK
WITHIN NIH OR OTHER AGENCIES AND
OTHER INSTITUTIONS TO SEE WHAT
WE CAN DO TO FURTHER VALIDATE
THESE TECHNOLOGIES.
SIMILARLY, THE OTHER AREA OF
INTEREST IS LUPUS NEPHRITIS, A
HUGE UNMET NEED WHERE THERE'S A
LOT OF WORK THAT IS YET TO BEGUN
AND WE BELIEVE THAT WE HAVE A SOLUTION
THAT COULD PROVIDE ANSWERS, AND
WE'RE WORKING ON THAT.
AGAIN, I THINK THERE'S ALWAYS
ROOM FOR FURTHER -- WORKING
CLOSELY WITH NIH AND OTHER
INSTITUTIONS ON TAKING SOME OF
THESE FORWARD.
BY WAY OF GENERAL SUGGESTIONS, I
THINK THIS CONFERENCE ITSELF IS
A GREAT WAY TO GET PEOPLE AROUND
AND DISCUSS SOME OF THESE
ISSUES.
I THINK IT WOULD BE GREAT IF WE
CAN HAVE SOMETHING LIKE THIS ON
A PERIODIC BASIS.
I'M NOT SURE IF THERE IS ALREADY
SUCH AN INSTITUTION, BUT SOME
KIND OF AN NIH INDUSTRY
COLLABORATORY GROUP THAT CAN
FURTHER SOME OF THESE OBJECTIVES
AND GOALS WOULD BE ANOTHER
SUGGESTION THAT WE WOULD HAVE.
AND WITH THAT, I WANT TO JUST
STOP HERE, THANK EVERYBODY, AND
HAPPY TO TAKE ANY QUESTIONS, AND
DR. HASNI, I'M HANDING IT BACK
TO YOU.
>> THANK YOU SO MUCH.
SO THAT WAS GREAT, AND AGAIN,
REMINDER IS THAT PLEASE PUT YOUR
QUESTIONS IN THE -- SORT OF THE
TEAL BAR ACROSS YOUR SCREEN FOR
THAT LIVE INTERACTION AND YOU'LL
GET Q & A AT THE END OF THE
SESSION.
NEXT IS DR. PETER BURBELO.
PLEASE TAKE IT AWAY.
>> CAN YOU SEE MY SCREEN?
>> YES, WE CAN SEE YOUR SCREEN.
>> HOW ABOUT RIGHT NOW, ARE WE
GOOD TO GO?
>> WE ARE GOOD.
>> GOOD AFTERNOON.
MY NAME IS PETER BURBELO.
I'M GOING TO BE TELLING YOU
REALLY A LOT MORE BASIC
INFORMATION ABOUT ANTIBODY
PROFILING AND AUTOIMMUNE AND
INFECTIOUS DISEASES, AND I WILL
TOUCH UPON A LITTLE BIT OF MY
INTERACTIONS WITH COMPANIES.
AGAIN, MY RESEARCH FOCUSES ON
USING A TECHNOLOGY I DEVELOPED
TO MEASURE ANTIBODIES, AND JUST
A LITTLE REFRESHER HOOR ON THE
LEFT, ANTIBODY, OF COURSE, ARE
TARGETING DIFFERENT PROTEINS AND
MOST PICK UP REALLY THESE LINEAR
EPITOPES REALLY WELL, BUT THE
CONFIRMATIONAL EPITOPES REQUIRE
PROPER FOLDING.
I'VE SORT OF SOLVED THAT ISSUE
BY DEVELOPING A TECHNOLOGY THAT
I CALL LUCIFERASE
IMMUNOPRECIPITATION SYSTEMS OR
LIPS FOR SHORT THAT USES
CHIMERIC ANTIGENS AS SHOWN HERE,
I BUILD CUSTOM-MADE ANTIGENS IN
MA NAILIAN EXPRESSION FACTORS
AND EXPRESS THEM IN CELLS.
BECAUSE THE ANTIGEN IS DIRECTLY
TAGGED WITH THIS LUCIFERASE
REPORTER, I DON'T NEED TO PURIFY
IT SO I CAN BUILD A TEST REALLY
QUITE QUICKLY, AS FAST AS I CAN
CLONE IT IN.
AND I'VE USED THAT TO MEASURE
ANTIBODIES IN THE SOLUTION PHASE
ASSAY, CAPTURED WITH BEADS AND
THE OUTPUT IS THIS LIGHT UNIT.
SHOWN ON THE RIGHT IS SORT OF
THE TYPICAL TYPE DATA THAT
YOU'LL BE SEEING, IS THAT OVER
QUITE A WIDE DYNAMIC RANGE OF
DETECTION, I CAN DETECT THESE
VISIBLE LIGHT UNITS AS SHOWN
HERE.
SO BEING AT NIH, I CAN DO SORT
OF ONE-STOP SHOPPING.
THERE'S SO MANY PEOPLE WORKING
ON SO MANY DIFFERENT HUMAN
DISEASES AND INFECTIOUS
DISEASES, AND SO I'VE BUILT
PROBABLY OVER 1500 TARGETS FOR
AUTOIMMUNE INFECTIOUS DISEASE,
AS I MENTIONED, I CAN PRODUCE
THESE REALLY QUICKLY, AND I TEST
THEM IN A 96-WELL FORMAT,
PROVIDING THIS REALLY HIGH
DEFINITION OUTPUT.
I'VE HAD A BIG FOCUS ON
AUTOIMMUNE TESTING, AS I'LL GET
INTO IT.
PUBLISHED A LOT, OVER 130 PAPERS
ON LOTS OF AGENTS.
I HAVE SEVERAL PATENTS,
INCLUDING ONE I'LL TALK ABOUT
VERY QUICKLY THAT USES THESE
MAGNETS FOR REALLY ULTRA RAPID
DETECTION OF ANTIBODIES, BUT MY
OVERARCHING GOAL REALLY IS TO
TRY TO DEVELOP A PANORAMIC
ANTIBODY SCREEN, SO LET'S GET
STARTED.
SO HERE'S AN EXAMPLE HERE ON THE
LEFT OF A REAL PROBLEM WE HAVE.
THERE ARE A LOT OF PEOPLE WITH
LYME DISEASE.
IT'S ABOUT A $500 MILLION
MARKET, AND BACK OVER A DECADE
AND A HALF AGO, I SCREENED A
BUNCH OF LYME ANTIGENS AND
BASICALLY ENDED UP IDENTIFYING
SEVERAL ANTIGENS THAT ARE USEFUL
AND I MADE A CONGLOMERATE
ANTIGEN.
AS YOU CAN SEE HERE, IT PICKS UP
REALLY QUITE NICE, AGAIN, ON
THIS LOG 10 SCALE, ALL OF THE
LIME PATIENTS AS BEING POSITIVE
WITH THIS CUTOFF BEING THE
DOTTED LINE.
AND COMPARED TO THE EXISTING
BEST ASSAY OUT THERE, WHICH HAS
76% SENSITIVITY, SO AGAIN,
PICKING UP ONLY ABOUT 76% OF THE
SAMPLES, I COULD PICK UP 94%
WITH 100% SPECIFICITY.
JUST SHOWING I COULD BUILD A
BETTER TEST.
MY INTERACTION WITH THE COMPANY
IS THE COMPANY THOUGHT THE
TARGET WAS REALLY GREAT AND THEY
LICENSED IT, BUT I THINK THEY'RE
WORKING ON IT BUT HAVEN'T HAD
TOO MUCH MORE INTERACTION.
BUT IT JI JUST GIVES YOU THE TYA
FLAVOR OF THE TYPES OF ASSAYS I
CAN BUILD.
DURING THE PANDEMIC, I WAS LUCKY
ENOUGH TO WORK WITH SOME OF THE
FIRST SAMPLES IN THE U.S.
INFECTED WITH SARS-COV-2, AND I
BUILT SORT OF IN REALTIME A
NUCLEIC CASS PID AS -- SPIKE, O0
STUDY, ONE OF PROBABLY 25,000
SAMPLES I ANALYZED, WE LOOKED AT
BOTH NUCLEIC CAPSID AND JUST
SHOWING YOU AGAIN THAT WE COULD
DETECT ANTIBODIES IN SOME OF
THESE PATIENTS REALLY QUITE
EARLY.
SO FOR INFECTIOUS DISEASE, I
CANNOT ONLY LOOK AT ONE ANTIGEN,
I CAN BUILD PANELS, FOR EXAMPLE,
THE HIV PROTEOME SHOWN ON THE
RIGHT, WE'VE USED THAT TO LOOK
AT DIFFERENT SUBSETS OF PEOPLE
WITH HIV, FOR EXAMPLE, ONE OF
THE FIRST PERSONS CURED OF HIV
CALLED THE BERLIN PATIENT HAS
REALLY LOW ANTIBODIES, BUT SO
AGAIN, USING THIS PLATFORM FOR
INFECTIOUS DISEASE IS REALLY
QUITE OBVIOUS.
WE HAVE EVEN USED TO IDENTIFY
NEW HUMAN PATHOGENS AS WELL AS
ANIMAL PATHOGENS USING THIS, WE
ACTUALLY WERE THE FIRST TO
DESCRIBE A HEPATITIS-LIKE C
VIRUS OUTSIDE OF PRIMATES.
BUT SO AGAIN, ONE VISION I HAVE
IS TO GET A COMPANY POTENTIALLY
TO BUILD THIS PANORAMIC SCREEN
FOR INFECTIOUS AND AUTOIMMUNE AS
YOU'LL SEE.
ANOTHER IS TO BUILD REALLY RAPID
TESTS, AND SO HBV16, AS MANY OF
YOU KNOW, CAN CAUSE HEAD AND
NECK CANCER, AND THERE WAS A
SMALL COHORT WHERE I USED
MULTIPLE ANTIGENS, I'M ONLY
SHOWING YOU ONE, THAT WE PICKED
UP SEVERAL, EIGHT OR NINE
PATIENTS WITH ANTIBODIES TO HPV,
MOST LIKELY DRIVING THE DISEASE,
AND USING THESE SAME LUCIFERASE
FUSION PROTEINS, I CAN DETECT
VERY, VERY RAPIDLY, IN ONE
MINUTE, MANY OF THOSE SAME
POSITIVES.
THE ASSAY ISN'T READY FOR PRIME
TIME, I'M STILL THINKING THERE'S
MAYBE A BETTER FORMAT, BUT I'M
JUST GOING TO LEAVE IT THERE.
SO AUTOIMMUNE DISEASES, AS YOU
MAY KNOW, PRESENT REALLY SEVERAL
CHALLENGES.
ONE INHERENT CHALLENGE IS THAT
THEY'RE OFTEN INCREDIBLY
HETEROGENEOUS AND YOU NEED
MULTIPLE ANTIGEN TARGETS TO PICK
UP POSITIVITY.
AGAIN, WE'VE DONE THAT IN TYPE A
PANEL THAT CAN PICK UP MOST OF
THE SAMPLES, AND THIS IS QUITE
OLD.
BUT MORE RECENTLY EVEN, ADULT
ONSET TYPE 1 DIABETES HAVE,
WE'VE DONE A STUDY WHERE WE CAN
DETECT THESE ANTIBODIES A DECADE
OR TWO DECADE BEFOREHAND.
IN CHILDREN, WE KNOW THESE
ANTIBODIES ARE PRESENT IN FIVE
TO 10 YEARS BEFORE THEY ACTUALLY
REQUIRE INSULIN, AND THERE'S NOW
AN FDA-APPROVED DRUG THAT
TARGETS CD3 THAT CAN DELAY THIS.
SO THERE'S BIG INTEREST IN
REALLY IDENTIFYING PATIENTS AT
RISK, AND WE'VE DONE SIMILAR
THINGS, I'M NOT GOING TO GO INTO
THE BIG DETAILS, BUT I IN LUPUS,
WE'VE IDENTIFIED DIFFERENT
SUBSETS AND IN SCLERODERMA,
WHICH IS EVEN MORE HETEROGENEOUS
WE'VE IDENTIFIED ALSO
INFORMATIVE ANTIGENS.
I'M JUST SHOWING YOU ONE PATIENT
HERE AT THE TOP, THIS THREE
CLUSTER UP HERE, USING SAMPLES
FROM THE ARMY ACROSS THE STREET,
BIOBANK SAMPLES.
SOME OF THESE PATIENTS HAVE
ANTIBODIES 27 YEARS BEFORE THE
ONSET, BEFORE THEY'RE DIAGNOSED
WITH SCLERODERMA.
OR 16, 17 YEARS, SO IT REALLY
SHOWS YOU THE OPPORTUNITY THAT
WE CAN HOPEFULLY HAVE.
ONE, BEING IN THE DENTAL
INSTITUTE, I'M PARTICULARLY
INTERESTED IN A DISEASE CALLED
SJOGREN'S DISEASE, WHICH CAUSES
ESSENTIALLY ORAL AND OCULAR
DRYNESS, TYPICALLY CHARACTERIZED
BY INFLAMMATION, AND AGAIN,
SHOWING YOU HOW A TEST I
DEVELOPED FOR ONE OF THE COMMON
ANTIGENS CALLED SSB THAT PICKS
UP ONLY 52% AND THE LIPS ASSAY
CAN PICK UP 76%.
SO HOW CAN ALL OF THESE PROFILES
BE USEFUL?
WELL, HERE'S ONE TO START WITH.
SO SJOGREN'S IS NOT ONLY A
DISEASE THAT AFFECTS JUST THE
SALIVARY GLAND, THEY HAVE
INCREASED RISK OF LYMPHOMA, AND
THEY HAVE A LOT OF DIVERSE EXTRA
GLANDULAR SYMPTOMS.
AND I'VE DEVELOPED THE PANEL OF
THESE SPECIFIC TARGETS IN
DIFFERENT TISSUES, SO FOR
EXAMPLE, ANTIBODIES TO AQUAPORIN
4 FOUND IN A FEW PATIENTS, AND
WE FOUND SOME OF THEM TO HAVE
NEUROPATHY.
THERE'S EVEN A SUBSET OF
PATIENTS WHO HAVE ANTIBODY TO A
RECEPTOR ON THE SURFACE THAT
ASSOCIATE WITH AUTONOMIC
DYSFUNCTION.
WE'VE HAD MARKERS OF THYROID,
LIVER, STOMACH, EVEN
INTERSTITIAL LUNG DISEASE.
AND SO AGAIN, I THINK THIS SORT
OF LOOKS AT SORT OF THE
PERSONALIZED DIAGNOSIS THAT IS
POSSIBLE USING THIS TECHNOLOGY.
BUT FOLLOWING ON ON SOME OF
THESE MARKERS, THE ONES THAT ARE
ON THE SURFACE, LIKE WHICH I
JUST TOLD YOU, CHOLINERGIC
RECEPTOR OR AQUAPORIN RECEPTOR,
AGAIN, IF THERE ARE ANTIBODIES
TO PROTEINS THAT ARE ON THE
SURFACE, WE GENERALLY THINK OF
THEM AS POTENTIALLY BEING
PATHOGENIC BECAUSE THE ANTIBODY
CAN DISRUPT THE SIGNALING OR THE
FUNCTION OF THAT PROTEIN ON THE
SURFACE, AS WELL AS PROTEINS
THAT ARE SECRETED.
ANYTHING THAT'S REALLY
EXTRACELLULAR HAS ACCESS TO
THESE ANTIBODIES, AND I'VE BEEN
ON A BUNCH OF PAPERS WHERE WE
WERE SORT OF THE FIRST TO
DESCRIBE ANTICYTOKINE ANTIBODIES
ASSOCIATED WITH OPPORTUNISTIC
INFECTION IN A BUNCH OF
DIFFERENT DISEASES.
WE'VE FOUND, INTERESTINGLY IN
COVID TIMES, THESE SAME
ANTIBODIES TURNED OUT TO BE
REALLY A MAJOR MORBIDITY MARKER
CAUSING MORBIDITY AND MORTALITY
OF OLDER MEN AND COVID.
BUT AGAIN, IF THE ANTIBODY, SOME
OF THESE MOLECULES ARE QUITE
LARGE AND DIFFICULT TO DETECT
ANTIBODIES TO, AND SO THERE'S A
REAL OPPORTUNITY, AGAIN, WITH
LIPS TO DETECT THESE ANTIBODIES.
I'M JUST SHOWING YOU HERE ON THE
LEFT THAT YOU CAN ACTUALLY
MONITOR PROTEINURIA IN PATIENTS
WITH AUTOIMMUNE KIDNEY DISEASE.
YOU CAN SEE ON THE RIGHT, Y
AXIS, PATIENT IS EXCRETING ABOUT
10 GRAMS OF PROTEIN AND THE
ANTIBODY IS STILL ABOVE THIS
DOTTED BLUE LINE, AND IF YOU
TREAT THIS PATIENT, YOU SEE HOW
NICELY THESE TWO TRACK.
HERE'S A PATIENT THAT'S
UNDERGOING RELAPSE AND
REMITTING.
YOU CAN SEE HOW THE ANTIBODY
ACTUALLY IN SOME CASES CAN
PREDICT THE RELAPSE.
AND SO THIS IS REALLY QUITE
EXCITING IN THE FIELD OF
MEMBRANOUS, THIS SEEMS TO BE ONE
OF THE WAYS THAT YOU DON'T NEED
TO DO BIOPSY, YOU CAN SORT OF
TRACK THE DISEASE.
ONE OF THE LAST THINGS I WANT TO
SORT OF LEAVE YOU WITH IS
THERE'S A BIG OPPORTUNITY IN THE
FACT THAT THIS PROBABLY
UNRECOGNIZED AUTOIMMUNITY IN
MANY DISEASES, ESPECIALLY THESE
PATHOGENIC ANTIBODIES THAT CAN
ACTUALLY CAUSE DISEASE.
THIS IS A STUDY THAT'S ONGOING
AND EXPANDING, IS THAT WE FOUND
THAT ABOUT 25% OF HIV PATIENTS
HAVE ANTIBOL DETO THE
CD4 RECEPTOR.
AGAIN, HIV BINDS TO THAT
RECEPTOR AND IT'S KEY, AND THESE
ANTIBODIES APPEAR TO BE
PATHOGENIC BECAUSE, AGAIN, IF
YOU HAVE THESE ANTIBODIES, YOUR
REBOUND OF CD4 COUNTS IS MUCH,
MUCH IMPAIRED COMPARED TO
PATIENTS WHO DO NOT HAVE THESE
ANTIBODIES.
SO AGAIN, THIS IS SORT OF STILL
AN EVOLVING AREA OF PATHOGENIC
ANTIBODIES IN DIFFERENT
DISEASES.
SO I JUST AGAIN WANT TO END AND
SAY THAT I'VE HAD SOME
INDUSTRIAL COLLABORATIONS, BUT
MAINLY THEY'RE INTERESTED IN A
SINGLE TARGET.
MY GOAL IS POTENTIALLY FOR
DEVELOPMENT OF SOME TYPE OF
PANORAMIC SCREENING PLATFORM,
AND WE COULD PROPOSE TO USE THAT
FOR BETTER DIAGNOSIS AND
TREATMENT.
MANY OF THE AUTOANTIBODIES AND
AUTOIMMUNE DISEASE ARE PRESENT
YEARS BEFORE, SO WE CAN USE
THOSE TO POTENTIALLY INTERVENE
IN THE AUTOIMMUNE DISEASE, AND
WE'VE ALSO AS I SHOWED YOU IN
THE MEMBRANOUS SOME OF THESE
ANTIBODIES GO UP AND DOWN AND
ARE GREAT MARKERS IN RESUMMONS
RESPONSE TOTREATMENT.
I'LL STOP THERE.
THANK YOU VERY MUCH.
>> THANK YOU SO MUCH, PETE TER.
TR.THAT WAS AN EXCELLENT OVERVIW
OF THE WORK THAT YOU'VE DONE AND
SOME POTENTIAL COLLABORATIONS
AND SO FORTH.
NOW I WOULD REQUEST DR. LEPTAK
TO PLEASE TAKE IT AWAY.
THANK YOU.
>> THE PREVIOUS PRESENTER, IF
THEY COULD STOP SHARING THEIR
SCREEN?
I'M NOT ABLE TO SHARE.
THERE WE GO.
HOPEFULLY EVERYONE CAN SEE THE
SCREEN?
>> WE CAN SEE THE SCREEN BUT WE
ARE LIKE IN THE PRESENTER'S --
>> THERE WE GO.
>> OKAY, PERFECT.
>> EXCELLENT.
THANK YOU ALL FOR THE
OPPORTUNITY TO PARTICIPATE IN
THE PANEL DISCUSSION TODAY.
AS BASED ON MY BACKGROUND, I
THINK WHAT I BRING TO THE
CONVERSATION IS THE UTILITY AND
IMPORTANCE OF THE COLLABORATION,
BUT THEN BRINGING IN ONE OF THE
SISTER AGENCIES AS PART OF THE
OVERALL DISCUSSION, THAT WOULD
BE NAMELY THE FDA.
CERTAINLY JUST TO BORROW AN OLD
ADAGE, IT REALLY DOES TAKE A
VILLAGE TO IDENTIFY AND
ULTIMATELY -- THAT INCLUDES A
BROAD ARRAY OF PARTNERSHIPS FROM
INDUSTRY, NIH, FDA, PATIENT
ADVOCACY, ET CETERA.
AND IT'S THOSE COLLABORATIVE
EFFORTS THAT ULTIMATELY YIELD
THE GREATEST FRUIT BECAUSE IT'S
ALMOST IMPOSSIBLE FOR A GIVEN
ENTITY JUST BASED ON RESEARCH
LIMITATIONS ALONE TO DEVELOP A
BIOMARKER THAT ULTIMATELY CAN
HELP A PATIENT POPULATION,
EITHER THROUGH DRUG DEVELOPMENT
OR DIAGNOSTIC DEVELOPMENT, ET
CETERA.
MUCH LIKE ALL OF MY TALKS, WHILE
I WAS AT THE FDA, I'M CERTAINLY
NO LONGER SPEAKING FOR THE FDA.
NOR AM I SORT OF ENDORSING A
PARTICULAR COMPANY POSITION AND
I DON'T HAVE ANY DISCLOSURES.
SO CERTAINLY AS YOU'VE SEEN FROM
THE TALKS TODAY, THE BIOMARKERS
ARE ACCEPTED TO BEI BE OF A BROD
VARIETY, INCLUDING MOLECULAR,
HISTOLOGIC, RADIOGRAPHIC,
DIGITAL, ET CETERA.
ALL OF THOSE FALL INTO THE
RUBRIC OF A DEFINED
CHARACTERISTIC THAT'S BEEN AT
THE CRUX OF HOW FDA AND OTHER
AGENCIES HAVE LOOKED AT
BIOMARKERS FOR DECADES.
AND THE KEY ASPECT HERE IS THE
DEFINED CHARACTERISTIC PIECE OF
THIS.
SO I THINK IT'S IMPORTANT
WHETHER YOU'RE IN INDUSTRY OR IN
NIH THAT YOU REALLY SIT DOWN AND
ARTICULATE WHAT YOU MEAN BY THE
BIOMARKER.
BECAUSE THE TERM KIND OF COMES
UP VERY LOOSELY, SO FOR
INSTANCE, ARE YOU TALKING ABOUT
A CHANGE FROM BASELINE, ARE YOU
TALKING ABOUT A CHANGE OVER
TIME, ARE YOU TALKING ABOUT A
MEAN CHANGE.
YOU KNOW, ALL THOSE KIND OF
NUANCES BECOME IMPORTANT AS YOU
START TO LOOK AT THE DATA THAT
YOU'RE COLLECTING AND HOW IT
MIGHT BE ADMISSIBLE AS PART OF A
FUTURE DRUG DEVELOPMENT EFFORT.
I WOULD ALSO LIKE TO DRAW
ATTENTION TO A COLLABORATIVE
EFFORT THAT I WAS INVOLVED WITH
AS PART OF NIH AND FDA, AND THAT
WAS THE DEVELOPMENT OF THE BEST
RESOURCE, WHICH IS ON THE
NATIONAL LIBRARY OF MEDICINE.
IT'S PERIODICALLY UPDATED,
BASICALLY INCLUDES CONSENSUS
DEFINITIONS IN THE BIOMARKER
SPACE, AND THERE'S OTHER
ANCILLARY INFORMATION THERE THAT
I THINK IS VERY HELPFUL.
SO I JUST WANTED TO HIGHLIGHT
FOR THOSE THAT MIGHT NOT BE
AWARE.
WHAT'S UNIQUE ABOUT THE
REGULATORY ASPECT OF BIOMARKERS
IS THAT ALTHOUGH BIOMARKERS ARE
USED BY MANY DIFFERENT
COMMUNITIES INCLUDING CLINICAL
AND BASIC SCIENCE AND THE LIKE,
WHEN YOU TALK ABOUT THE
INCLUSION OF BIOMARKER
INFORMATION IN A DRUG PROGRAM,
WHETHER OR NOT IT'S
REGULATORY-READY, QUOTE-UNQUOTE,
THERE ARE KIND OF THREE CORE
FACTORS THAT COME INTO PLAY.
ONE IS AROUND THE
REPRODUCIBILITY OF THE DATA, AND
THAT ULTIMATELY SCIENCE IS A
COLLABORATIVE PROCESS, AND
ULTIMATELY YOU START FROM THE
PUBLISHED SCIENTIFIC LITERATURE,
AT LEAST THAT'S WHAT MOST FOLKS
DO.
THAT LITERATURE, YOU KNOW, HAS
ITS VALUE BUT THERE ARE ALSO
CHALLENGES IN THAT THERE'S A
HIGH RATE OF DISCORDANT
INFORMATION IN THE LITERATURE
AROUND BIOMARKER DATA.
MUCH OF THAT COMES FROM NOT
NECESSARILY THAT ANY GIVEN LAB
HAD DONE SOMETHING RIGHT OR DONE
SOMETHING WRONG, BUT EACH DID SO
DIFFERENTLY, AND THE METHOD
SECTION OF SCIENTIFIC
PUBLICATIONS ARE USUALLY NOT
SPECIFIC ENOUGH TO KIND OF DO
METADATA ANALYSIS ACROSS STUDIES
AND THE LIKE.
AND ONE OF THOSE MAIN PROBLEMS
IS AROUND THE USE OF THE
MEASUREMENT METHOD OR THE
ANALYTIC, ESPECIALLY FOR ANY
TYPE OF A NOVEL BIOMARKER,
THERE'S LIKELY NOT AN EXISTING
ASSAY OR DEVICE, SO THESE ARE
BEING HOME-GROWN IN THE LABS
WHERE THESE ARE BEING STUDIED,
WHICH IS PERFECTLY FINE, BUT AS
THAT MATURES, THE ANALYTIC
PERFORMANCE CHARACTERISTICS
BECOME MORE AND MORE IMPORTANT,
AND IT'S ALWAYS A CHICKEN AND
EGG PROBLEM, HOW MUCH DO YOU
INVEST IN THE PERFORMANCE OF
YOUR ANALYTIC WHEN YOU DON'T
KNOW IF THE BIOMARKER IS
VALUABLE OR NOT.
SO THAT IS KIND OF ONE OF THE
CHALLENGES.
THE OTHER IS THAT CERTAINLY AS
TECHNOLOGY BECOMES MORE COMPLEX
AND INNOVATIVE, IT ALSO BECOMES
LESS PORTABLE, IF YOU WILL, ANDT
FROM A BIOMARKER DEVELOPMENT
PERSPECTIVE IS WHETHER OR NOT
IT'S GOING TO BE USED IN A DRUG
PROGRAM AND ULTIMATELY LEAD TO
THAT DRUG'S APPROVAL, WILL THAT
TECHNOLOGY IN FACT BE AVAILABLE
FOR PRESCRIBERS SO THEY CAN
ULTIMATELY DECIDE WHETHER OR NOT
A GIVEN PATIENT SHOULD OR SHOULD
NOT GO ON A THERAPY.
AND THE WAY TO DO THAT, IF
THERE'S A BIOMARKER SELECTION OR
ROLE IN THAT DEVELOPMENT EFFORT
IS WHETHER OR NOT THAT TEST IS
ALSO AVAILABLE.
OR SOMETHING THAT'S AT LEAST
PERFORMING TO THE SAME STANDARD.
WHEN YOU'RE DOING COLLABORATIVE
EFFORT AROUND BIOMARKERS, I LIKE
TO THINK ABOUT THIS VERY SIMPLY.
ULTIMATELY SCIENCE AND MEDICINE
TO A LARGE DEGREE IS MORE OF AN
ART THAN A SCIENCE.
WE CERTAINLY KNOW WHAT WE KNOW,
BUT WHEN YOU'RE PUTTING TOGETHER
A CLINICAL PROGRAM, I THINK IT'S
REALLY HELPFUL TO ARTICULATE
WHAT ARE YOUR ASSUMPTIONS GOING
INTO THAT, ESPECIALLY AROUND
SOME OF THE KEY ASPECTS OF THE
CLINICAL TRIAL AND THAT COULD
INCLUDE THE BIOMARKER ITSELF,
METHOD OF MEASUREMENT, WHAT
POPULATION IS BEING ENROLLED AND
ALSO THE END POINT.
AND I THINK IF YOU CAN
ARTICULATE IN ADVANCE WHERE YOUR
ASSUMPTIONS LIE, IF THINGS DON'T
GO AS YOU HAD PLANNED, WHICH
UNFORTUNATELY HAPPENS MORE OFTEN
THAN NOT, IT ALLOWS YOU TO LEARN
FROM THOSE NEGATIVE RESULTS IN A
WAY, BUT IT'S DIFFICULT WHEN
THINGS DIDN'T GO WELL AND IF YOU
DO THAT SORT OF PRE-PLANNING,
THEN IT'S VERY EASY TO GET INTO
THESE POST HOC ANALYSES WHICH
KIND OF GO DOWN RABBIT HOLES AND
KIND OF UNDERMINE WHAT YOU COULD
HAVE LEARNED FROM THOSE NEGATIVE
RESULTS.
SO IN GENERAL, I WOULD SAY AS
YOU START ANY OF THESE EFFORTS,
WHATEVER THAT EFFORT MAY BE,
JUST TAKE THE TIME TO PUT IN THE
EFFORT UP FRONT AROUND THE CORE
ELEMENTS AND WHAT YOU KNOW, WHAT
YOU THINK YOU KNOW, AND WHAT YOU
NEED TO KNOW IN ORDER FOR THIS
TO BE HELPFUL IN THE FUTURE.
IT'S HELPFUL AROUND A BIOMARKER
TO TALK ABOUT ITS CONTEXT OF
USE.
THE EXAMPLES THAT ARE GIVEN HERE
ARE FROM A CLINICAL TRIAL
PERSPECTIVE, BUT THESE COULD BE
MODIFIED FOR WHATEVER YOUR USE
MAY BE.
MANY OF THE USE CASES INVOLVE
IDENTIFYING THE RIGHT PATIENT
POPULATION THAT YOU WANT TO
ENROLL IN YOUR STUDY.
AS WAS MENTIONED BY SOME OF THE
PREVIOUS PRESENTERS, MANY
DISEASE ENTITIES HAVE A
HETEROGENEITY PROBLEM, SO ONE OF
THE THINGS YOU CAN DO WITH THE
BIOMARKER DATA IS TO HELP TO
HOMOGENIZE THE PATIENTS THAT ARE
ENROLLED SO THEY'RE MORE SIMILAR
THAN DISSIMILAR, AT LEAST AS A
PROOF OF CONCEPT SO THAT YOU CAN
KIND OF BUILD FROM THERE.
IT A BIT OF A KIND OF
INTERESTING CONVERSATION WITH
THE AGENCY.
ULTIMATELY THEY WANT A DRUG TO
BE STUDIED IN AS BROAD A
POPULATION AS POSSIBLE.
BUT I THINK IN THE EARLY PROOF
OF CONCEPT STAGE, THEY'RE
CERTAINLY OPEN TO HAVING A MORE
HOMOGENEOUS POPULATION TO AT
LEAST IDENTIFY THE PROOF OF
CONCEPT, AND THEN YOU CAN EXPAND
FROM THERE.
WHEN YOU WANT TO VALIDATE A
BIOMARKER, ULTIMATELY IT'S THE
BENEFIT AND RISK OF HOW THAT
BIOMARKER IS USED IN A CLINICAL
TRIAL CONTEXT THAT DETERMINES
WHAT TYPE OF DATA IS NEEDED TO
SUPPORT THAT USE.
AND ESSENTIALS FOR A VALIDATION
EFFORT IS AGAIN THE SPECIFICITY
OF THE BIOMARKER DEFINE WHAT YOU
MEAN BY THE BIOMARKER IN GREAT
DETAIL, AND THERE'S RESOURCES
AVAILABLE ON BEST THAT TALK
ABOUT THE DIFFERENT COMPONENTS
OF A BIOMARKER DESCRIPTION.
YOU WANT TO SPECIFY THE TOOL OR
INSTRUMENT AND ULTIMATELY THE
SETTING IN WHICH IT WOULD BE
USED AND THEN TRY TO THINK
THROUGH THE POTENTIAL BENEFITS
AND RISKS ONE THING TO HIGHLIGHT
MORE GEARED TOWARDS THE
RESEARCHERS BUT IT ALSO APPLIES
TO INDUSTRY, IF THERE'S A
BIOMARKER AND/OR ASSOCIATED
MEASUREMENT METHOD OUT THERE,
AND SORT OF MARKETED IN
SOMETHING YOU CAN PURCHASE AS A
KIT OR OTHERWISE DOESN'T MEAN
THAT IT'S REGULATORY-READY FOR
USE OUTSIDE OF THE CONTEXT IN
WHICH IT WAS DEVELOPED.
SO JUST BECAUSE YOU EITHER HAVE
A TEST OR A BIOMARKER IN ONE
POPULATION, HOW IT'S BEING USED
IN A DIFFERENT DISEASE
POPULATION OR A DIFFERENT
CONTEXT DOESN'T MEAN YOU HAVE TO
START FROM SCRATCH, BUT YOU MAY
HAVE TO DO SOME ADDITIONAL
ANALYTIC AND/OR CLINICAL
VALIDATION TO MAKE SURE THAT
TEST IS REGULATORY-READY FOR ITS
NEW INTENDED USE.
ULTIMATELY WHEN YOU'RE TALKING
ABOUT A DISEASE AND THE
BIOMARKERS AND HOW THEY MAY
INTERPLAY AS PART OF A CLINICAL
DEVELOPMENT EFFORT, I THINK IT'S
HELPFUL TO KIND OF GO THROUGH
QUICKLY A PARADIGM WHERE YOU
TALK ABOUT A NORMAL PHYSIOLOGY
THAT CHANGES ULTIMATELY BECOMES
DEFINED BY A DISEASE THROUGH
CONSENSUS DEFINITIONS OF SIGNS
AND SYMPTOMS.
IF THAT DISEASE IS CHRONIC, IT
MAY HAVE PERIODS WHERE IT'S
BEING ACTIVE OR QUIESCENT SO YOU
MAY WANT TO MONITOR IT, AND ALSO
IF IT IS CHRONIC AND THERE'S
LONG-TERM SEQUELAE FROM HAVING
THAT DISEASE, YOU ALSO WANT TO
LOOK AT PROGNOSTIC BIOMARKERS
AROUND FUTURE COMPLICATIONS.
AND THEN ONCE A THERAPY IS IN
PLAY, YOU CERTAINLY ARE GOING TO
WANT TO LOOK AT OFF-TARGET
EFFECTS FROM A SAFETY
PERSPECTIVE, YOU'RE GOING TO
WANT TO SHOW PROOF OF CONCEPT,
AND THEN ULTIMATELY WHETHER OR
NOT THERE'S SOMETHING BENEFICIAL
TO THE PATIENT THAT IS
CLINICALLY MEANINGFUL.
ONE AREA OF COLLABORATION THAT I
WOULD HIGHLIGHT WHERE NIH AND
OTHER COLLABORATIONS WITH COME
INTO PLAY IS AROUND THIS NORMAL
PHYSIOLOGY PIECE.
SO IF YOU IDENTIFY A BIOMARKER
OF INTEREST AND YOU WANT TO KNOW
WHAT IS THE NORMAL VARIATION,
OUTSIDE OF ANY OTHER IMPACT,
CERTACERTAINLY OUTSIDE OF A DRUG
CONTEXT, YOU WANT TO KNOW OVER
THE COURSE OF A DAY, OVER THE
COURSE OF GENDER, ETHNICITY,
WHAT ARE ALL THE FACTORS THAT
IMPACT WHAT THE NATURAL
VARIABILITY OF THAT BIOMARKER
MAY BE.
MANY TIMES THAT IS ONE OF THE
STSTUMBLING BLOCKS FOR MANY NOVL
BIOMARKER DEVELOPMENT EFFORTS
BECAUSE TO GATHER THAT
INFORMATION USUALLY TAKES TIME
AND RESOURCES THAT A GIVEN
ENTITY DOESN'T HAVE.
AND SO IT'S THAT TYPE OF NORMAL
BIOLOGY, WHILE NOT SECTI -- WHIT
SEXY AND MANY TIMES NOT FUNDED
IT'S CRITICAL FOR A BIOMARKER
STUDY TO DETERMINE HEY, IS THE
CHANGE I'M SEEING ABOVE AND
BEYOND NORMAL VARIATION, AND
MORE IMPORTANTLY, IS THAT CHANGE
ABOVE AND BEYOND NORMAL
VARIATION MEANINGFUL TO THE
PATIENT, HOW IS IT BENEFITING
THEM?
AND IF YOU DON'T KNOW WHAT THAT
NORMAL VARIATION IS, IT'S KIND
OF HARD TO HAVE A USEFUL
CONVERSATION AROUND IT.
SO I'M GOING TO END WITH TWO
SLIDES, JUST BASED ON MY TIME
WITH THE FDA AND COLLABORATING
WITH NIH, WITH INDUSTRY, WITH
SMALL BIOTECH, WITH PATIENT
GROUPS AND NOW MY ROLE AS A
PHARMACEUTICAL CONSULTANT WHERE
THESE COLLABORATIVE EFFORTS ARE
STILL VERY MUCH IN PLAY.
THE FIRST IS INADEQUATE AND
INAPPROPRIATE PLANNING.
SO ULTIMATELY YOU CAN HAVE THE
BEST IDEAS BUT IF YOU DON'T HAVE
THE RESOURCES, TIME OR FUNDING
TO COMPLETE THAT FULL STUDY,
REALLY SCALE BACK YOUR EFFORTS
TO SOMETHING THAT'S ACHIEVABLE
WITHIN THE RESOURCES AND TIME
THAT YOU HAVE.
MANY TIMES I THINK PEOPLE GO IN
WITH THE BEST INTENTIONS BUT
THEY DON'T ACHIEVE THEIR GOAL
AND THEY DON'T ACHIEVE SOMETHING
AS A MILESTONE BECAUSE THEIR
GOALS DIDN'T MATCH WHAT THEIR
OPPORTUNITIES WERE AT THE
BEGINNING.
I VERY MUCH WANT TO DO A CALLOUT
AROUND THE VALIDATION METHOD FOR
THE BIOMARKER AND HOW YOU'RE
MEASURING IT AND INTERPRETING
IT.
IF THIS ISN'T SOME TYPE OF
LABORATORY-DEVELOPED TEST OR LDT
IN A LAB AND YOU'RE DOING YOUR
BEST AS PART OF AN INITIAL
BIOMARKER DEVELOPMENT EFFORT,
JUST ALWAYS BE AWARE THAT ANY
DECISIONS YOU'RE MAKING BASED ON
THAT BIOMARKER ARE VERY
DEPENDENT UPON THE QUALITY OF
THE ASSAY EMPLOYED.
AND YOU MAY MAKE DECISIONS THAT
ARE WRONG JUST BASED ON THE FACT
THAT THE ANALYTIC METHOD IS NOT
UP TO THE SPECS NEEDED.
ALSO JUST BE CAREFUL OF
OVERINTERPRETING FROM DIFFERENT
RESOURCES, AS I SAID IN THE
PUBLISHED LITERATURE, MANY TIMES
SOME OF THE STUDIES ARE NOT
REPRODUCIBLE.
GREAT PLACE TO START BUT NOT
ALWAYS THE BEST PLACE TO END.
THERE'S A LOT OF INFORMATION
THAT'S OUT THERE THAT'S PUBLIC
FROM A REGULATORY PERSPECTIVE,
AND IT REALLY WOULD ENCOURAGE
YOU, WHATEVER YOUR GOALS ARE, TO
LOOK AT THOSE RESOURCES, BECAUSE
THEY REALLY ARE QUITE HELPFUL.
SO IN THE BIOMARKER DEVELOPMENT
SPACE, BASED ON THE CURES
LEGISLATION BACK IN 2017, NOW
THE SUBMISSIONS ARE MADE PUBLIC
AND FDA'S GUIDANCE AND
RECOMMENDATIONS ARE ALSO MADE
PUBLIC.
AND THE INFORMATION IS IN A
SEARCHABLE DATABASE, SO WHETHER
YOU'RE DOING AN IMAGING
BIOMARKER OR SOMETHING IN THE
DIGITAL ARENA, WHY NOT LOOK AT
THE ADVICE THAT OTHER GROUPS ARE
RECEIVING AND THEN APPLY TO YOUR
OWN DEVELOPMENT EFFORT.
EVEN IF YOU HAVE NO DESIRE TO
INTERFACE WITH FDA, I JUST THINK
IT'S GOOD SCIENTIFIC PRACTICE
THAT THESE KIND OF EXCHANGES
TAKE PLACE AND PEOPLE CONSIDER
THEM.
THE SECOND IS CERTAINLY IN THE
BIOMARKERS, MANY FOLKS ARE
TRYING TO GET DRUGS TO PATIENTS
FASTER, ESPECIALLY WHEN THEY
DON'T HAVE EXISTING THERAPY OR
INADEQUATE THERAPY AND THEY'RE
LOOKING AT NOVEL SURROGATES AND
THERE'S AN OPPORTUNITY TO LOOK
AT THOSE RESOURCES TO SEE, HEY,
AM I HITTING ALL OF THE RELEVANT
AREAS THAT AT LEAST A REGULATOR
IS CONCERNED ABOUT?
FINAL WILL BE AROUND DATA
MANAGEMENT.
MAKE SURE YOU TRY TO PRESPECIFY
YOUR PROTOCOLS, YOUR S.O.P.s
AND DOCUMENT SO THAT ULTIMATELY
IF THERE'S A QUESTION ON THE
DATA ITSELF OR EVEN BETWEEN
LABS, YOU CAN KIND OF GO BACK
AND SEE WHERE THE PROBLEMS MAY
HAVE ARISEN.
THE OTHER THING I WOULD
ENCOURAGE, AND THIS IS FOR THE
LONGITUDINAL EFFORTS AROUND
NATURAL HISTORY STUDIES AND THE
LIKE, REALLY GO OUT OF YOUR WAY
TO MAKE SURE THAT YOU'RE USING
CASE DEFINITIONS FOR THE DISEASE
THAT ARE BROADLY ACCEPTED AND
THAT YOU'RE USING DATA STANDARDS
WHEN THEY EXIST.
ONE OF THE BIGGEST CHALLENGES AT
LEAST THAT WE HAD AT THE FDA
WHEN TRYING TO FIND WHAT IS THAT
NATURAL VARIABILITY, WE WOULD GO
TO NIH WHERE THEY WOULD BE DOING
THESE DECADES-LONG NATURAL
HISTORY STUDIES ONLY TO FIND OUT
THAT WE COULDN'T USE THE DATA
BECAUSE EITHER THE CASE
DEFINITION FOR THE DISEASE
DEPARTMENT MATCH WHAT'S BEING
DONE IN CLINICAL TRIALS OR THAT
THE DATA STANDARDS WERE EITHER
NOT THERE OR DIFFERENT.
SO IT REALLY IS HELPFUL IF WE
THINK OF THIS AS A COMMUNITY
EFFORT, THINK OF NOT ONLY YOUR
OWN NEEDS, BUT THOSE OF THE
COMMUNITY, BECAUSE THAT'S GOING
TO BE CRITICAL FOR ANY TYPE OF
ADVANCEMENT IN THE FIELD.
AND THEN FINALLY, WHEN YOU'RE
DOING YOUR BIOMARKER DEVELOPMENT
EFFORT, CERTAINLY FOR INVESTORS,
ALWAYS TO SAY WHY YOU'RE NEW,
WHILE YOU'RE NOVEL, THE EXACT
OPPOSITE, WHAT MAKES MY PROJECT
SIMILAR TO OTHERS RATHER THAN
WHAT MAKES IT DIFFERENT.
IN ALL SERIOUS ANY, YOUR IDEA
MAY NOT BE ALL THAT SPECIAL AND
THAT'S A GOOD THING, NOT
NECESSARILY A BAD THING.
AND WITH THAT, I LOOK FORWARD TO
YOUR QUESTIONS.
>> GREAT.
THANK YOU SO MUCH, DR. LEPTAK,
FOR A WONDERFUL PRESENTATION AND
ALL OUR PANELISTS FOR SHARING
THEIR WISDOM AND INSIGHT.
AS WE REFER TO A QUESTION, I
THINK WE'LL START OUT AND I'LL
ASK EACH OF OUR PANELISTS TO
SORT OF ANSWER, MAYBE WITH A
ONE-LINER, A GENERAL QUESTION
THAT WHAT CAN BE DONE TO IMPROVE
THE PROCESS OF BUILDING A
PARTNERSHIP BETWEEN NIH, IRB AND
INDUSTRY, WHAT WOULD BE ONE
THING THAT YOU MAY SUGGEST OR
ONE THING THAT WE SHOULD FOCUS
ON FROM THE NIH SIDE OR THE
INDUSTRY SIDE?
SO I'LL START WITH RICHARD AND
THEN KIND OF GO DOWN HOW WE
PRESENTED.
>> SURE, THANKS.
I THINK ONE THING IS JUST
AWARENESS FROM THE NIH SIDE, BUT
MY COLLEAGUES AT LEAST AT KNOW
NOVARTIS, THERE WASN'T UNIVERSAL
KNOWLEDGE OF THE NIH CLINICAL
CENTER AND THE TYPES OF DISEASE
THAT ARE STUDIED AND HOW
COLLABORATIONS COULD GO.
I THINK ON THE NIH SIDE, THE KEY
THING FOR ME, AND IT CAME UP IN
ONE OF THE QUESTIONS, IS JUST
TRYING TO HAVE THE TYPES OF
AGREEMENTS A LITTLE BIT MORE IN
LINE WITH THE REST OF THE WORLD.
SO NIH, I THINK AS FAR AS I CAN
TELL, IS TRULY UNIQUE, WHICH IS
NOT A GOOD THING, IN TERMS OF
CRADAs AND CLINICAL TRIAL
AGREEMENTS.
AND THEN -- SO TRYING TO
HARMONIZE A LITTLE BETTER WOULD
I THINK GO A LONG WAY.
>> THANK YOU, RICHARD.
SEAN?
>> I'M TELLING YOU, I CANNOT
AGREE WITH YOU MORE.
EVEN WITHIN THE NIH, DIFFERENT
INSTITUTES HAVE JUST -- THEIR
APPROACH COULD BE A LITTLE
DIFFERENT.
AS AN NIH INVESTIGATOR, YOU
ALMOST COME WITH THAT IDEA IN
MIND.
WE PARTNERED WITH CARE DX, ONE
OF THE COMPANIES THAT WORK ON
CELL FREE DNA.
IT IS GREAT THAT WE BUILD
RELATIONSHIPS, SO SOMETIMES YOU
SEE THEM LITERALLY HITTING THEIR
HEAD ON THE WALL, AND I THINK
OUR REGULATIONS FOLLOW
GOVERNMENT RULES.
IT LITERALLY TAKES AN ACT OF
CONGRESS TO CHANGE THEM.
BUT YOUR POINT IS WELL TAKEN,
THAT OUR RULES NEED TO SOMEHOW
ALIGN WITH THE REST OF THE WORLD
AND IT DELAYS OUR PARTNERSHIP
WITH INDUSTRY, I COULD NOT AGREE
MORE.
>> I THINK THERE'S A QUESTION
RELATED TO THAT SPECIFIC POINT,
BUT WE'LL COME TO THAT A LITTLE
BIT LATER AND MAYBE I'LL ASK
RICHARD IF HE CAN ANSWER THAT.
BUT MOHAN, DO YOU HAVE ANY
INSIGHT OR ANYTHING YOU WOULD
SAY, ONE THING THAT WE CAN
CHANGE?
>> ABSOLUTELY, DR. HASNI.
FROM MY PERSPECTIVE, IT'S HOW DO
WE MAKE THIS MORE
BUSINESS-FRIENDLY, RIGHT,
PARTICULARLY FOR STARTUPS.
AND AGAIN, THEY HAVE UNIQUE
CHALLENGES IN EVERYTHING FROM
FUNDING TO DEALING WITH SYSTEMS
AND VARIOUS OTHER
CONSIDERATIONS.
AND THAT WOULD BE MY SUGGESTION,
ANYTHING THAT WE CAN DO TO
GETTING THOSE PROCESSES WHEN IN
DOUBT, THAT WOULD BE GREAT.
GLL PETER, ANYTHING FROM YOUR
SIDE?
>> I THINK I HEARD THIS EARLIER,
BUT I WAS EXTRAMURAL BEFORE I
CAME TO NIH, AND I HAD DEVELOPED
A TECHNOLOGY, AND WHEN I APPLIED
TO A TOP UNIVERSITY, THEY WERE
GOING TO SPIN A COMPANY, AND SO
I THINK IT'S THAT -- WE DON'T
HAVE THAT DNA AT NIH SO MUCH,
THAT, YOU KNOW, WE'RE MORE INTO
RESEARCH AND NOT REALLY PUSHING
IT OUT THE DOOR, THE REAL TEST,
AND I THINK THERE'S SO MANY
BARRIERS TO EVEN -- LEGALLY, YOU
CAN'T DO THAT.
SO I'LL STOP THERE.
>> THANK YOU.
CHRIS, DO YOU HAVE ANY ONE-LINER
ADVICE?
>> YEAH, I WOULD SAY -- I WOULD
ECHO WHAT I HAD SHARED DURING MY
TALK, THAT IT'S THE THESE LONGIL
NATURAL HISTORY STUDIES THAT ARE
SO IMPORTANT ESPECIALLY IN THE
RARE DISEASE INTAIS AS SPACE AS
OTHERS, THAT THOSE TYPE OF
EFFORTS, MANY TIMES ARE
SPEARHEADED BY NIH AND ITS
COMMUNITY, THAT WHEN YOU'RE
DESIGNING THOSE TRIALS, TO THINK
BROADLY AND HAVE AS MANY INPUTS
ON WHAT DATA IS COLLECTED AND
HOW SO THAT IT HAS THE GREATEST
UTILITY.
>> THANK YOU SO MUCH.
SO THERE ARE A NUMBER OF
QUESTIONS THERE, I THINK TWO
QUESTIONS, THE FIRST IS
SPECIFICALLY FOR RICHARD ABOUT
HOW SENIOR DO THE PHARMA
CHAMPIONS HAVE TO BE IN ORDER TO
MAKE THINGS HAPPEN?
RICHARD, DO YOU WANT TO RESPOND
TO THAT?
>> YEAH, SURE.
SO I THINK IT REALLY DEPENDS
WHAT KIND OF AGREEMENT YOU'RE
TALKING ABOUT.
IF IT'S AN AGREEMENT WHERE YOUR
LAB, AN NIH LAB WOULD
COLLABORATE WITH A RESEARCH
GROUP AT A COMPANY TO SAY DO
TRANSLATIONAL RESEARCH ON A
DISEASE MODEL WITH A TOOL
COMPOUND, THAT IS A SCIENTIST TO
SCIENTIST KIND OF BILATERAL
THING AND IT DOESN'T NEED HIGH
LEVEL SUPPORT SO THE SCIENTIST
YOU WOULD BE MEETING WOULD
LIKELY BE THE SCIENTIST THAT
WOULD THEN BE THE CHAMPION ON
THE COMPANY SIDE.
BUT THE MANAGEMENT GETS INVOLVED
BUT THAT, I THINK IS MORE
STREAMLINED.
FOR THE LARGE CONSORTIA OR FOR
CLINICAL TRIAL AGREEMENT, THAT'S
WHERE YOU NEED USUALLY HIGHER
LEVEL SUPPORT, IF IT'S A
CONSORTIA, IT'S GREAT BUT THIS
IS A MULTIMILLION DOLLAR
COMMITMENT ON THE SIDE OF EACH
SPONSORING COMPANY, SO THAT JUST
TAKES A LOT OF TRY ANGULATION,
HAVING PUSHED ONE OF THOSE
THROUGH AND THEN THE CLINICAL
JUST USUALLY TAKES A HIGHER
LEVEL BECAUSE AS WE'LL MAYBE
TALK ABOUT, THAT'S ONE OF THE
HARDEST AGREEMENTS TO GET SIGNED
WITH NIH INTRAMURAL.
EXPWR THANK YOU SO MUCH.
I THINK SOMEBODY COMMENTED FROM
OUR EARLIER DISCUSSION THAT WE
HAD, IS THAT -- REDUCE THE SBIR
GRANT REVIEW TIME, SO ONE OF THE
THINGS WE CAN DO
PROGRAMMATICALLY.
THANK YOU SO MUCH, RICHARD.
I THINK ONE THING THAT HAS BEEN
HIGHLIGHTED BOTH FROM NIH SIDE
AND FROM OUR OUTSIDE INDUSTRY
PANELISTS IS SOME NIH AGREEMENTS
OR DOING BUSINESS WITH NIH IS
NOT INDUSTRY-FRIENDLY.
AND THERE IS A QUESTION HERE
WHICH MAYBE I WOULD ASK CHRIS,
RICHARD AND PERHAPS MOHAN TO
RESPOND, THAT THERE IS A
CONSISTENT THEME THAT IT'S NOT
INDUSTRY-FRIENDLY.
SO NOW SOMEWHAT FROM -- SOMEONE
FROM INSIDE NIH IS ASKING WHY
INDUSTRY AGREEMENTS ARE NOT
PREPARED IN A MANNER THAT'S --
THEY'RE THE SOLE BURDEN OF
MAKING THEM FEDERALLY COMPLIANT,
SO IT'S KIND OF TURNING IT
AROUND TO YOUR SIDE.
RICHARD, CHRIS, MOHAN, ANY OF
YOU WANT TO ANSWER THIS?
>> YEAH, I CAN GO.
SO FROM OUR EXPERIENCE, ONE OF
THE KEY CHALLENGES HAS ALWAYS
BEEN TECHNOLOGY.
HOW DO WE KIND OF -- MEET
FEDERAL STANDARDS IN TERMS OF
WHAT TECHNOLOGICAL STANDARDS HAD
TO BE MAINTAINED.
NOW, I'M NOT SAYING -- THERE ARE
OBVIOUSLY GOOD REASONS WHY THESE
STANDARDS SHOULD BE IN PLACE,
BUT YOU KNOW, THE STANDARDS ARE
EXTREMELY HIGH, AND SO THAT'S
SOMETHING THAT WE HAVE
EXPERIENCED AND I THINK THESE
MAY BEING SOME OF THE THINGS
THAT CAN BE ADDRESSED IN A
DIFFERENT WAY.
MAYBE IT'S A FIREWALL APPROACH,
MAYBE THERE ARE WAYS THAT WE CAN
WORK IN A WAY THAT THIS COULD BE
SOLVED.
SO THAT WOULD BE MY FEEDBACK.
>> CHRIS, YOU WERE SAYING
SOMETHING?
>> IT'S NOT SO MUCH FROM AN
INDUSTRY PERSPECTIVE BUT
CERTAINLY WHEN I WAS STILL AT
THE FDA, JUST THE CRADAs AND
THE LIKE SHARING INFORMATION,
EVEN BETWEEN INTERGOVERNMENTAL
AGENCIES WAS A BIT OF A
NIGHTMARE.
SO UNFORTUNATELY I THINK THIS IS
A BROAD PROBLEM, THAT MAYBE
GOVERNMENT IS THE MAIN
CHALLENGE, NOT NECESSARILY NIH.
>> MAYBE JUST TO MENTION THAT I
THINK IT'S A LITTLE BIT OF A
MYTH AROUND THE NIH, THE ONLY
REASON THE NIH AGREEMENTS ARE
UNFRIENDLY IS BECAUSE OF FEDERAL
LAW, BECAUSE AROUND THE TIME
WHEN I WAS CLINICAL DIRECTOR
BEING, LOOKING AROUND OTHER
PARTS OF GOVERNMENT, THE
VETERANS' ADMINISTRATION, ALSO
PART OF THE GOVERNMENT, IS MUCH
MORE FRIENDLY TO CLINICAL TRIALS
THAN NIH.
SO I THINK THERE IS A POTENTIAL
FOR CHANGE.
IT'S JUST THERE'S A LOT OF, I
THINK, RESISTANCE TO CHANGE
BECAUSE - TO CHANGE TEMPLATES IS
JUST HARD.
BUT OTHER PARTS OF THE
GOVERNMENT WHICH DO CLINICAL
RESEARCH ARE MORE
RESEARCH-FRIENDLY, AND, YOU
KNOW, JUST -- I WAS VERY -- I
DIALED IN TO MONICA'S TALK, NIH
DIRECTOR, AND I HEARD A LOT OF
ENTHUSIASM FOR MAKING IT MORE
USER-FRIENDLY, AND I THINK IT
WILL JUST TAKE SOME DOING.
SO I THINK THAT'S NOT AN
UNCHANGEABLE PROBLEM BUT WE'LL
NEED CHANN CHAMPIONS, SENIOR CHS
INSIDE NIH FOR CHANGE.
>> I THINK I'LL ASK MAYBE PETER,
THEN SEAN AND CHRIS, YOU CAN ADD
ON TO THAT, IS THAT ANYONE -- IS
THERE ANY BIOMARKER -- ABOUT
VARIOUS ETHNIC GROUPS, DO YOU
THINK THAT THE BIOMARKERS ARE
DIFFERENT AMONG DIFFERENT ETHNIC
GROUPS, WHAT BIOMARKERS ARE
KNOWN TO BE DIFFERENT IN
DIFFERENT POPULATIONS?
ANY IDEAS FROM YOUR SIDE, PETER
OR SEAN, CHRIS, ANY OF YOU,
PLEASE?
>> YEAH, WE DO SEE DIFFERENCES
IN DIFFERENT ETHNIC GROUPS IN
SCLERODERMA, THERE'S A
PREPONDERANCE OF DIFFERENT
ANTIBODIES.
I WOULD SAY THERE IS DEFINITELY
EVIDENCE OF THAT.
I WOULD JUST LEAVE IT AT THAT.
IT'S COMPLICATED, IS I GUESS THE
SHORT ANSWER.
>> ABSOLUTELY.
CERTAINLY IN TERMS OF DRUG
METABOLIZING ENSOIMS WI EN -- ES
WITHIN THE LIRCH, THE SIPs,
THERE'S A LOT OF HETEROGENEITY
BASED ON WHAT'S FOUND IN THOSE
PROCESSING GENES, AS JUST ONE
EXAMPLE.
>> THANK YOU.
>> AND I WOULD MAYBE JUST ADD --
GO AHEAD.
>> PLEASE GO AHEAD.
>> NO, NO, GO AHEAD.
>> I'LL FOLLOW UP ON THAT POINT
ABOUT DRUG METABOLISM.
IN TRANSPLANTATION, FOR EXAMPLE,
PATIENTS OF AFRICAN DESCENT WILL
HAVE THE SAME LEVELS OF BLOOD,
THE SAME LEVELS OF DRUG IN BLOOD
AS PATIENTS OF EUROPEAN DESCENT.
HOWEVER, THEY HAVE MUCH LOWER
DRUG ACTIVITY THAN THEIR
COUNTERPARTS, EVEN THOUGH THEY
TAKE MAYBE HIGH DOSES TO GET
THOSE SAME LEVELS, THEY
CLEARLY -- RACIAL DIFFERENCES
THAT ARE THERE.
BUT IF YOU TWIST IT ANEAR WAY,
ANOTHER WAYWITH THAT, THE ORIGIS
AND BIOMARKERS WERE DEVELOPED IN
POPULATIONS THAT DID NOT -- WERE
NOT AS DIVERSE, HOWEVER, THEY
HAVE BEEN APPLIED NOW IN
POPULATIONS THAT ARE QUITE
DIVERSE.
I THINK THAT'S ANOTHER MISSION,
HOPEFULLY FOR ANOTHER DAY, THAT
NIH CAN LOOK INTO A LITTLE BIT.
THERE'S CLEARLY ETHNIC/RACIAL
DIFFERENCES, BUT NOT SURE
WHETHER IT'S THE WAY WE STUDIED
THE BIOMARKERS IN THE FIRST
PLACE, OR WHETHER IT'S SOMETHING
ELSE.
>> RICHARD?
>> I AGREE WITH EVERYTHING
THAT'S BEEN SAID.
I THINK AS A COMPANY THAT DOES
CLINICAL RESEARCH ALL OVER THE
WORLD IN DOZENS OF COUNTRIES,
THIS IS CRITICAL AND CAN BE A
SOURCE OF A LOT OF PROBLEMS.
SO POLYMORPHISMS BEING HIGHLY
DIVERGENT AROUND THE WORLD IS
ONE MAJOR ONE.
I THINK THERE ARE SOME
POLYMORPHISMS CLEARLY LINKED TO
ETHNIC GROUPS, APOL1 IS A
CLASSIC ONE, WE NOW KNOW THAT
UNDERLIES PROBABLY A LOT OF THE
CORE RENAL SURVIVAL, EVEN IF
PATIENTS WITH -- AS WELL AS
OTHER KIDNEY DISEASES SO THAT'S
HIGHLY ENRICHED IN THE AFRICAN
ORIGIN POPULATION, ASIAN
POPULATION HAVING A NUMBER OF
IMPORTANT PHARMACOGENOMIC
POLYMORPHISMS, AND IF WE DON'T
TAKE THAT INTO ACCOUNT, WE
ALMOST ALWAYS STRATIFY OUR
TRIALS BY SIGHT BEC SITE BECAUSL
FOR THAT AT LEAST BY THE
ENROLLMENT SITE.
JAPAN HAS A UNIQUE REGULATORY
REQUIREMENT.
THEY ASSUME THAT THERE'S
ETHNIC-SPECIFIC DRUG
INTERACTIONS THAT'S UNIQUE, BUT
WE CAN'T JUST -- IT'S NOT JUST A
JAPAN ISSUE.
>> THANK YOU SO MUCH.
SO WE ONLY HAVE A COUPLE OF
MINUTES LEFT.
THERE IS ONE MORE QUESTION, I
GUESS, CHRIS IT SEEMS MORE PERT
NEPT TOPERTINENT TO YOU, PROTEOD
BIOMARKER IN DRUG DISCOVERY, WHY
WE ARE NOT SEEING MORE USE OF
PROTEOMICS AND WHAT WE CAN DO TO
ELIMINATE THESE BARRIERS, IF YOU
HAVE ANY COMMENTS ON THAT.
>> WELL, IT'S NOT THAT THEY'RE
NOT BEING PROPOSED.
THEY CERTAINLY ARE.
BY MANY COMPANIES AS PART OF
THEIR OVERALL DEVELOPMENT
EFFORT.
I THINK IT'S NOT THAT THE FDA IS
NOT OPEN TO A PROTEOMIC
SIGNATURE, IT'S THE COMPLEXITY
OF HOW THAT SIGNATURE IS
GENERATED AND HOW IT'S
INTERPRETED.
SO, YOU KNOW, THE MORE COMPLEX
SOMETHING GETS, IT JUST MEANS
YOU HAVE MORE VARIABLES THAT FDA
IS GOING TO BE LOOKING AT TO
MAKE SURE THAT THEY CAN LOOK AT
THE DATA AND UNDERSTAND WHAT IT
MEANS.
>> THANK YOU.
ALL RIGHT, ANYONE -- PLEASE GO
AHEAD.
>> JUST TO ADD REALLY QUICK JUST
BECAUSE WE WERE PRETTY DEEPLY
INVOLVED IN PROTEOMICS WITH
SIMOLOGIC, ONE OF THE COMPANIES
THAT DOES PROTEOMICS FOR
RESEARCH AND THEN HAS DEVELOPED
A COUPLE OF BIOMARKERS BASED ON
THAT.
I THINK THE KEY IS THAT LARGE
SCALE PROTEOMICS IS A DISCOVERY
TOOL WHICH WE USE A LOT, THEN
YOU NEED TO DO THE SAME HARD
WORK OF VALIDATION THAT CHRIS
MENTIONED OFTEN FOR SINGLE OR A
SMALL SET OF BIOMARKERS, SO IT'S
VERY RARE THAT WE USE THE
PROTEOMICS AS ITSELF, BUT
THEY'RE VERY VALUABLE, WE FOUND
REALLY ACTIONABLE WMHTS BIOMARKS
USING PROTEOMICS -- IN SERUM IS
SO MUCH MORE ACTIONABLE, EVEN IF
RNA SEQ IS COOLER, WHAT SEAN
TALKED ABOUT OR PETER, ANYTHING
THAT'S AN ANTIBODY CELL FREE
DNA, SO SEER OWM BIOMARKERS AR S
ARE WAY MORE ACTIONABLE SO
THAT'S WAY MORE BEYOND JUST
PROTEOMICS.
>> THANK YOU SO MUCH FOR THAT
CLOSING COMMENTS, AND THANK YOU
ALL OF THE PANELISTS AND FOR THE
ATATTENDEES AND AHMED FOR MANNIG
THE CHAT AND I THINK WE'RE
ALMOST OUT OF TIME SO THANK YOU
SO MUCH.
>> THANK YOU.
BYE-BYE.
>> WELL, WELCOME BACK TO THE
WEBINAR, EVERYONE.
WE HAVE COME TO THE END OF THIS
YEAR'S NIH INDUSTRY DAY.
SO IN THE COMING WEEKS,ING YOU
WILL GET A QUESTIONNAIRE THAT
WILL HELP US PLAN FOR FUTURE
ITERATIONS OF THIS EVENT, AND
PLEASE, PLEASE SEND US YOUR
EVALUATIONS, YOUR COMMENTS, YOUR
QUESTIONS, AND MOLES MOST OF ALR
IDEAS.
BUT FOR NOW, ON BEHALF OF THE
NIH INTRAMURAL RESEARCH PROGRAM,
MANY, MANY, MANY THANKS TO ALL
THE SPEAKERS, PANELISTS, AND
DISCUSSANTS, TO THE ENTHUSIASTIC
COMMITTEE MEMBERS, TO THE NIH
ASSEMBLY OF SCIENTISTS, AND THE
NIH OFFICES OF TECHNOLOGY
TRANSFER, AND TO OUR COLLEAGUES,
FROM PRECON EVENTS WHO HAVE
REALLY MADE THIS DAY GO WITHOUT
A HITCH.
AND THEN ESPECIALLY MANY THANKS
TO ALL OF YOU WHO SPENT THE DAY
WITH US, BUILDING SYNERGIES,
FORGING COLLABORATIONS.
YOU ARE CHARTING A FUTURE THAT
BRINGS SCIENCE, TECHNOLOGY, AND
COMMERCE TO BEAR ON THE HEALTH
AND WELL-BEING OF PEOPLE
EVERYWHERE.
FOR THAT, WE ARE EXCEPTIONALLY
GRATEFUL.
SO MANY THANKS, STAY WARM, AND
KEEP IN TOUCH.
AND NOW I'M GOING TO TURN THE
FLOOR OVER.
>> THANK YOU, NINA.
ACTUALLY NINA SAID WHAT I WAS
GOING TO SAY.
THANK YOU SO MUCH FOR ALL BEING
HERE.
WE HAD SOME FANTASTIC
CONVERSATIONS TODAY AND WE HOPE
TO CONTINUE THESE.
PLEASE BE ON THE LOOKOUT FOR A
VERY SHORT SURVEY.
IT SHOULD TAKE ONLY FIVE
MINUTES.
IT WILL GO OUT EITHER TODAY OR
TOMORROW.
IT WILL HAVE THE SAME FORMAT
THAT YOU'VE BEEN GETTING THE
OTHER EMAILS FOR THE EVENT FROM.
SO PLEASE TAKE FIVE MINUTES TO
RESPOND TO THIS.
IT'S VERY IMPORTANT FOR US TO
HEAR BACK FROM YOU, SO WE CAN MAKE THIS BETTER
HAVE A GREAT EVENING, EVERYONE.