HOW TO ADVANCE INNOVATIVE LUNG
AND SLEEP THERAPIES FOR PATIENTS
WITH HIGH UNMET NEEDS.
MY NAME IS MARRAH
LACHOWICZ-SCROGGINS FROM THE
PEDIATRIC DISEASES BRANCH AND
CO-ORGANIZER OF THE WORKSHOP AND
LOOKING FORWARD TO AN EXCITING
TWO DAYS TOGETHER.
BEFORE WE KICK OFF THE MEETING
WE'LL HAVE A BRIEF INTRODUCTION
FROM DR. MARISHKA BROWN THE
DIRECTOR OF THE NATIONAL CENTER
ON SLEEP DISORDERS RESEARCH.
>> BEFORE THAT I'M GOING TO GO
OVER THE HOUSEKEEPING.
GOOD MORNING.
THIS PRESENTATION IS BEING
RECORDED.
PLEASE MAINTAIN RESEARCH
INTEGRITY AND CONFIDENTIALITY.
DISCUSSION WITH OTHER WORKSHOP
PATIENTS AND ATTENDEES.
THE TOOL WILL BE USED FOR OPEN
DISCUSSION BETWEEN VIRTUAL
PARTICIPANTS AND COMMENTS
CAPTURED BY THE WORKSHOP
SPONSORS AND USE Q&A AND THE
NAME OF THE PERSON YOU'RE
DIRECTING YOUR QUESTION TO.
THIS COULD BE USED TO ASK
SPEAKERS A QUESTION AND THEY'LL
BE CAPTURED FOR REVIEW.
KINDLY STAY ON MUTE AND OFF
CAMERA.
THANK YOU.
>> THANK YOU FOR THE
INTRODUCTION.
AS MENTIONED MY NAME IS MARISHKA
BROWN THE DIRECTOR OF THE
NATIONAL CENTER ON SLEEP STOREDS
RESEARCH HOSTED WITHIN THE
NATIONAL HEART, LUNG AND BLOOD
INSTITUTE WELCOME TO HOW TO
ADVANCE INNOVATIVE LUNG AND
SLEEP THERAPIES TO PATIENTS WITH
HIGH UNMET NEEDS.
WE HOPE TO FACILITATE AN OPEN
DIALOGUE WITH THE PULMONARY
SLEEP COMMUNITIES AND CIRCADIAN
COMMUNITIES WITH THE GOAL OF
ADVANCING IDEAS AND STRATEGIES
TO MOVE THERAPIES FROM THE BENCH
TO CLINIC WHERE INVESTIGATIONAL
NEW DRUG OR DEVICES THAT REQUIRE
REGULATORY APPROVALS.
THE SPEAKERS ON TODAY'S AGENDA
WILL PROVIDE UPDATE ON
REGULATORY PATHWAYS INCLUDING
DESIGNATIONS SUCH AS FAST TRACK
AND BREAKTHROUGH THERAPY THAT
COULD EXPEDITE DEVELOPMENT FOR
INTERVENTIONS IN AREAS OF UNMET
NEED.
THIS INCLUDES HOW TO LEVERAGE
DISCUSSIONS WITH REGULATORY
BODIES AND FEEDBACK THAT GUIDES
THE DEVELOPMENT PROCESS.
SPEAKERS WILL EMPHASIZE THE NEED
TO FIND YOUR MARKET AND
HIGHLIGHT UNIQUE PRODUCTS IN
COMPARISON TO UNIQUE THERAPIES
IN PULMONARY AND SLEEP MEDICINE
AND NOVEL TECHNOLOGIES, IMPROVED
SAFETY PROFILES OR ENHANCED
EFFICACY.
WE'LL ALSO HEAR ABOUT WAYS TO
MOVE IDEAS FROM THE LABORATORY
THROUGH THE COMMERCIALIZATION
PROCESS AS DEVELOPING NEW
TREATMENTS REQUIRES SIGNIFICANT
RESOURCES INCLUDING TIME,
FINANCIAL INVESTMENTS AND TEAMS
OF RESEARCHERS AND EXPERTS TO
TRANSPORT A PRODUCT TO MARKET.
WE THANK YOU ALL FOR ATTENDING
TODAY.
AND WE LOOK FORWARD TO THE
DISCUSSION OVER THE NEXT TWO
DAYS AS WE DIG THROUGH AND HOPE
NOT ONLY THAT YOU PARTICIPATE IN
THE WORKSHOP BUT THAT YOU
ACTIVELY ENGAGE IN TOMORROW'S
BREAKOUT SESSIONS TO DISCUSS
BARRIERS AND FACILITATORS TO
TRANSLATING SCIENTIFIC FINDINGS
AND PULMONARY SLEEP MEDICINE AND
CIRCADIAN BIOLOGY INTO MEDICAL
INTERVENTIONS TO HELP PATIENTS
WHO NEED IT THE MOST.
BE
AGAIN, WE WOULD LIKE TO THANK
EACH OF YOU FOR YOUR ATTENDANCE
AND ACTIVE PARTICIPATION AND
I'LL TURN IT BACK TO THE
ORGANIZERS AND MARRAH AND OTHERS
JOHN SHER I DAN.
>> I WANT TO CONTINUE TO
INTRODUCE THE OTHER CO-ORGANIZER
OF THE WORKSHOP.
AS DR. BROWN NOTED, MY
COLLEAGUE, DR. JOHN SHERIDAN OF
THE RESTRICTIVE AND VASCULAR
DISEASES BRANCH WILL BE
CO-LEADING THIS MEETING.
WE ALSO HAVE TWO WONDERFUL
WORKSHOP CO-CHAIRS YOU'LL HEAR
FROM THROUGHOUT THE WORKSHOP.
FIRST IS DR. KATELYN KRIVCHENIA
OF THE INTERSTITIAL AND RARE
LUNG DEED PROGRAM AND DIRECTOR
OF THE INFANT SYSTEM FIBROSIS
PROGRAM AT NATIONWIDE CHILDREN'S
HOSPITAL.
SHE CARES FOR INFANTS AND YOUNG
ADULTS WITH A WIDE SPECTRUM OF
LUNG DISEASES.
OUR OTHER CO-CHAIR IS DR. JEFF
MOFFIT FROM CARBON BIO SCIENCES
AND ALSO HAS OVER 15 YEARS OF
PHARMACEUTICAL EXPERIENCE AND IS
A CERTIFIED TOX KOL FWIFT.
AND ALSO HAS EXPERIENCE ON
SEVERAL AREAS MAINLY FOCUSES ON
RARE DISEASES.
THE PURPOSE IS TO EDUCATE THE
RESEARCH COMMUNITY HOW TO BRING
THEIR IDEAS FROM THE BENCH TO
THE CLINIC.
WE ALSO WANT TO DISCOVERY
BARRIERS AND FACILITATORS FOR
INNOVATION IN DEVELOPING NOVEL
THERAPIES FOR LUNG AND SLEEP
CONDITIONS WITH HIGH DISEASE
BURDEN.
WE KNOW THERE'S A MISALIGNMENT
BETWEEN DISEASE BURDEN AND NOVEL
THERAPY INNOVATION AND SLOW
SPEED IN WHICH THEY'RE MAKING IT
TO MARKET AND MAY CONTRIBUTE TO
INCREASED MORBIDITY AND
MORTALITY AND EXACERBATE HEALTH
DISPARITIES AND CLOSING THESE
GAPS IN THE LUNG AND SLEEP
MEDICINE COMMUNITY NEEDS TO
HAPPEN THROUGH RESEARCH
COLLABORATIONS IN ORDER TO HELP
REDUCE THESE HEALTH DISPARITIES
AS WELL AS IMPROVE HEALTH
OUTCOMES AND LOWER SOCIETAL
COSTS.
WE ALSO ALREADY RECOGNIZE THAT
THERE ARE SEVERAL CHALLENGES WE
HOPE PARTICIPANTS CAN WEIGH IN
ON DURING THE BREAKOUTS TOMORROW
INCLUDING RECOMMENDS STRATEGIES
TO THE LUNG AND SLEEP RESEARCH
COMMUNITIES TO SPUR AND
FACILITATE INNOVATION THAT
ADDRESSES THE UNMET NEEDS AND
REDUCES HEALTH DISPAURTS.
SOME CHALLENGES INCLUDE WHAT IS
THE GREATEST UNMET NEEDS AND
UNMET NEEDS DUE TO A LACK OF
ACCESS TO EXISTING THERAPIES.
ALSO, DO WE UNDERSTAND ENOUGH
ABOUT THE DECISION MAKING
PROFESSION FOR INVESTMENT BY FOR
PROFIT AND PRIVATE SECTOR
DEVELOPERS AND THEIR POTENTIAL
RISK AND RETURNED?
WHERE DOES THE DRUG INVESTMENT
PIPELINE COME IN TO HELP SUPPORT
UNMET NEEDS WHERE STANDARD OF
CARE IS INADEQUATE FOR WHERE
OUTCOMES CAN BE POTENTIALLY
IMPROVED BY INNOVATIVE
THERAPIES.
FINALLY, THERE ARE STRATEGIES IN
THE COMMUNITY AND WE NEED TO
THINK ABOUT THESE TOGETHER IN
ORDER TO FACILITATE GREATER
INVESTMENT IN INNOVATION TO
CONTINUE TO ADDRESS THESE UNMET
NEEDS AS WELL AS TO DISCOURAGE
PRACTICES THAT IMPEDE
INNOVATION.
WE'RE HOPING TO DEMYSTIFY THE
PROCESS FROM WHICH YOU'RE
GETTING YOUR IDEAS THROUGH THE
REGULATORY AND COMMERCIALIZATION
PIPELINES AND THE FOCUS OF THIS
WORKSHOP WILL BE THE IND
ENABLING PATHWAY WHICH IS THE
PATHWAY WHICH YOU'LL TAKE YOUR
IDEAS THROUGH RELEVANT MODEL
SYSTEMS INCLUDING PKPD AND
TOXICOLOGY STUDIES, THINKING
ABOUT HOW YOU'LL ACCESS CAPITAL
TO MOVE TO MANUFACTURING AND
PRODUCTION TO ENTER CLINICAL
TRIALS.
YOUR IND PACKAGE WILL REQUIRE
CLINICAL PROTOCOLS FOR THE
TRIALS.
AT THAT POINT YOU'LL NEED TO
PARTNER WITH PATIENTS AND PEERS
IN THE COMMUNITY WHO MAY HAVE
BEEN SUCCESSFUL IN THIS PROCESS.
YOU'LL CONTINUE TO SEE THESE
THEMES THROUGHOUT THE WORKSHOP .
AS DR. BROWN MENTIONED IN THE
AGENDA WE'LL PROVIDE AN UPDATE
TO PATHWAYS AND DESIGNATION MAY
HELP EXPEDITE INTERVENTIONS IN
AREAS OF UNMET NEEDS.
THIS WILL CONTINUE TO HELP YOU
LEVERAGE YOUR DISCUSSIONS WITH
REGULATORY BODIES AND USE THE
FEEDBACK THEY GIVE YOU FOR
DEVELOPING YOUR INNOVATIONS.
WE WILL HEAR FROM SPEAKERS WHO
WILL EMPHASIZE MARKET AS
DR. BROWN MENTIONED.
THIS MEANS AN INVESTIGATIONAL
PRODUCT YOU MAY BE WORKING ON
NEEDS TO BE UNIQUE TO THERAPIES
IN PULMONARY AND SLEEP MEDICINE
AND NOVEL TECHNOLOGIES THAT HAVE
IMPROVED SAFETY PROFILES OR
ENHANCED EFFICACY.
YOU ALSO NEED TO THINK ABOUT HOW
TO MOVE YOUR IDEAS FROM THE
BENCH THROUGH THE
COMMERCIALIZATION PROCESS.
DEVELOPING YOUR TREATMENT WILL
REQUIRE SIGNIFICANT INVESTMENT
AND IF THE MARKET SEEMS LIMITED
MAY DETER INVESTMENT FROM
POTENTIAL PARTNERS.
TOMORROW WE'LL CONTINUE TO
ENGAGE STAKEHOLDERS AND RELEVANT
FEDERAL AGENCIES AND ACADEMICS
AND CLINICIANS AND PATIENT
GROUPS AND INDUSTRY TO BUILD
CAPACITY AND INNOVATION IN
THERAPEUTIC DEVELOPMENT AND
ENSURING BROAD EQUITABLE ACCESS
FOR SAFE AND EFFECTIVE NOVEL
THERAPIES.
WE WANT PARTICIPANTS TOE NOT
ONLY LEARN FROM THIS WORKSHOP
BUT TO NETWORK WITH EACH OTHER.
AS WE MENTIONED EARLIER, WE DO
HAVE THE CHAT OPEN FOR YOU TO
CONNECT TO EACH OTHER DURING THE
WORKSHOP.
ADDITIONALLY, WE WILL HAVE THE
ZOOM ROOM OPEN FOR TWO
NETWORKING BREAKS DURING THE
MEETING.
AND FINALLY AS I SAID EARLIER,
WE HOPE YOU'LL PARTICIPATE IN
THE BREAKOUT SESSIONS ON DAY 2
TO HELP US DETERMINE THE
BARRIERS AND FACILITATORS TO AID
IN FINDINGS AND CIRCADIAN
BIOLOGY INTO MEDICAL
INTERVENTIONS FOR PATIENTS WHO
NEED THEM MOST.
I'D LIKE TO TURN IT OVER TO OUR
MEETING CO-CHAIR, DR. MOFFITT.
>> TODAY I WANT TO DISCUSS THE
EARLY CONCEPTS YOU CAN LEVERAGE
TO IMPROVE THE QUALITY OF
CLINICAL CANDIDATES EARLY IN THE
RESEARCH AND DEVELOPMENT
PROCESS.
MANY APPROACHES CAN GO TO
TRANSLATIONAL ASPECTS OF EARLY
DRUG DEVELOPMENT.
OBVIOUSLY PATIENT SAFETY
CONSIDERATIONS ALWAYS COME FIRST
AND IT'S NEVER TOO EARLY TO
START TO THINK ABOUT SAFETY
PROFILES FOR EARLY POTENTIAL
DRUGS IN THE PROCESS.
IF YOU WERE TO OPEN A BOOK YOU'D
SEE TARGET ORGANS AND TEXAS
TOXICITY AND THE RANGE OF DOSES
AND WE'RE TRYING TO FEED THIS TO
CLINICAL COLLEAGUES ON WHAT TO
LOOK OUT FOR IN PATIENTS.
SPECIFICALLY A PRESUMED
EFFICACIOUS DOSE AND AT THE
SAFETY MARGIN LOOKS LIKE TO
WHERE ADVERSE EFFECTS MAY START
CREEPING IN.
OF COURSE WE INCLUDE SOME SAFETY
MARGINS JUST TO ADDRESS
UNCERTAINTY AS YOU'LL HEAR ABOUT
TODAY.
AND WHAT I HOPE TO SHOW YOU OVER
THE SLIDES ARE THE CONCEPTS YOU
CAN LEVERAGE EARLY ON TO BE
TRANSPARENT WITH YOUR PATIENTS,
YOUR CLINICAL COLLEAGUES AND
REGULATORS TO SHOW THEM HOW YOU
ARRIVED AT THE RECOMMENDATIONS.
BUT I HAVE TO SAY THE LONGER I'M
IN THE BUSINESS THE LESS I
BELIEVE DRUG SAFETY IS JUST THIS
TWO-DIMENSIONAL RISK VERSUS
BENEFIT CON SEFT.
-- CONCEPT.
SO THIS IS REALLY HOW I THINK OF
DRUG SAFETY AND IT'S HIGHLY
INFLUENCED BY YOUR PERSONAL
EXPERIENCE, THE NOVELTY AND
SEVERITY OF THE DRUGS THAT
YOU'RE GOING AFTER AND CERTAINLY
THE SIZE AND PHILOSOPHY OF YOUR
ORGANIZATION.
WHAT SOME CONSIDER TO BE RISK
ACCEPTABLE AND IN A FATAL RARE
DISEASE YOU'LL HAVE A DIFFERENT
PERSPECTIVE THAN IN SOMETHING
LIKE JUVENILE ASTHMA WHERE
THERE'S GOOD SAFE DRUGS OUT
THERE ALREADY.
SO, THESE ARE SOME OF THE
CONCEPTS YOU HAVE TO CONSIDER
MOVING FORWARD.
SO AS MOST OF US AT THE WORKSHOP
ARE FROM ACADEMIC, GOVERNMENT OR
SMALL BIO TECH, WE CAN'T
POSSIBLY HOPE TO LEVERAGE ALL
THE RESOURCES AT THE DISPOSAL OF
BIG PHARMA COMPANIES.
THEY'RE INCENTIVED AND THEY HAVE
A WEALTH OF COMPOUNDS PRESUMABLY
OF MOVING FORWARD AND WE DON'T
HAVE THE LUXURY OF THOSE OPTIONS
AND OFTEN ARE MORE PERSISTENT
WITH OUR LIMITED ASSETS TO BE
MORE RISK TOLERANT OFTEN OUT OF
NECESSITY TAKING TIME TO
UNDERSTAND THE BARRIERS BETWEEN
US AND THE CLINIC AND UNDERSTAND
THE STRENGTHS AND WEAKNESSES
ASSETS.
SPENDING MORE TIME TO DIVE IN
THE MECHANISM, FINDING NOVEL
WAYS AND ASSAYS TO REALLY ASSESS
THIS TO DRIVE FORWARD THROUGH
THE ISSUES.
IN EITHER SITUATION I'M
CERTAINLY NOT ADVOCATING AROUND
TAKING AN UNSAFE MEDICINE
FORWARD BUT I'M JUST REALLY
MAKING IT CLEAR THAT RISK
TOLERANCE IS DIFFERENT DEPENDING
ON WHERE YOU STAND IN THE
PROFESSION AND I WOULD ARGUE
THAT'S A VERY GOOD AND IMPORTANT
THING WHERE WE BOTH BENEFIT FROM
EACH OTHER.
HERE'S AN OVERVIEW OF THE
PROCESS FOR THE TYPICAL SMALL
MOLECULE.
WE'LL FOCUS ON THE DRIVE TO THE
IND AS MARRAH MENTIONED AND
THAT'S YOUR INVESTIGATIONAL NEW
DRUG APPLICATION YOU SUBMIT WITH
THE FDA OR IND.
WE'LL HAVE REGULATORY FOLKS TALK
TO US ABOUT WHAT THE MILESTONES
MEAN AND WHAT YOU NEED TO GET
THERE.
ONE OF THE THINGS WE WANT TO
FOCUS IN ON TOMORROW IS AROUND
THE CLINICAL DEVELOPMENT AND
ASSESSMENT STANDPOINT AS YOU
DRIVE TOWARD AN APPROVAL.
SO MAYBE IF YOU COULD MOVE TO
THE NEXT SLIDE WE'LL TALK MORE
SPECIFICALLY AROUND THINGS YOU
CAN START TO THINK ABOUT FROM A
DRUG SAFETY STANDPOINT VERY
EARLY IN THE PROFESSOR.
-- PROCESS.
I WOULD ARGUE THE EARLIER YOU
CAN THINK OF DRUG SAFETY THE
BETTER OFF YOU'LL BE.
OFTEN IT WORKS COLLABORATELY --
COLLABORATIVELY TO GUIDE THE
PHARMACOLOGY AND CAN IMPROVE THE
QUALITY OF THE CANDIDATES THAT
ARE VERY COST EFFECTIVE.
WHILE TOXICOLOGISTS CAN CLEARLY
DEFINE WINNERS AND LOSERS IN THE
PROCESS WE CAN INDICATE
COMPOUNDS THAT OFTEN HAVE MORE
DRUG-LIKE CHARACTERISTICS TO USE
TO THEN PRIORITIZE AND HELP
STEER THAT RESEARCH PROCESS AS
THE EFFICACY AND TRANSLATIONAL
ASPECTS OF YOUR PROGRAM ARE
EVOLVING IN PARALLEL.
I THINK SOME OF THE IMPORTANT
THINGS TO THINK ABOUT ARE HOW
CAN YOU DO THESE AT LOW DOLLAR
COST OPPORTUNITIES TO REALLY
DRIVE THOSE FORWARD AND REALLY
MAKING A WEIGHT OF EVIDENCE
APPROACH TO IMPROVE THE QUALITY
OF THE CLINICAL CANDIDATES.
I DO WANT TO TAKE A MOMENT TO
FRAME WHAT SUCCESS LOOKS LIKE
EARLY IN DRUG SAFETY.
THERE WAS A GREAT PAPER FROM
OLSON IN 2000 THAT FOUND
CONDUCTING THE LONGEST TERM THE
PIVOTAL TOXICOLOGY STUDY, 26
WEEK IN A RODENT AND 39 WEEK IN
A LARGE ANIMAL SPECIES WAS ONLY
ABLE TO IDENTIFY 71% OF HUMAN
RELEVANT TOXICITIES WHEN YOU
CONSIDER THE FINDINGS OF BOTH OF
THOSE PIVOTAL STUDIES.
THIS IS NOT INCLUDING ALL THE
ADDITIONAL TOXICOLOGY STUDIES
FOR GENE TOX, SAFETY
PHARMACOLOGY AND OTHERS GET YOU
TO 80% OF BEING ABLE TO PICK OUT
HUMAN RELEVANT TOXICITIES.
SO AS YOU CONSIDER THIS IT'S
ACTUALLY QUITE SOBERING TO
REMEMBER THAT MEANS 20% OF THE
TIME HUMANS ARE THE SENSITIVE
SPECIES.
THIS MEANS NO MATTER WHAT YOU
DO, WHAT ASSAYS YOU PROFILE, YOU
COULD NOT PREDICT THESE
TOXICITIES WITH ANY AVAILABLE
ASSAY.
AS SOBERING AS THAT IS YOU CAN
THINK OF TURNING THIS AROUND THE
OPPOSITE WAY AROUND WHAT TRYING
TO GUIDE YOU AND WHAT ASSAYS TO
RUN AS PART OF THIS.
AT SOME POINT YOU'RE NO LONGER
GENERATING VALUABLE DATA.
YOU'RE JUST GENERATING MORE DATA
TO ASSESS AND NOT NECESSARILY
ADDING DECISION MAKING CRITERIA.
IF YOU GO TO ANY OF THESE
SCIENTIFIC CONFERENCES OR I'M
SURE YOUR IN BOX BOMBARDED BY
ASSAY COMPANIES SAYING RUN THESE
ASSAYS TO HELP YOU UNDERSTAND
THIS, HOWEVER, YOU HAVE TO
UNDERSTAND AT SOME POINT YOU'RE
HAVING THIS EFFECT OF
DIMINISHING RETURNS.
THIS IS ONE OF THE STRENGTHS OF
OUR NEXT SESSION YOU'LL HEAR
ABOUT HOW CERTAIN FOLKS HAVE
DEVELOPED ASSAYS ENRICHING THE
DECISION MAKING CRITERIA THAT
DON'T FIT INTO THE TRADITIONAL
WAYS NECESSARY OF ARRIVING AT A
DRUG CANDIDATE.
AND I THINK THIS IS SO IMPORTANT
TO THINK ABOUT BECAUSE THE
EARLIER THAT YOU CAN PARTNER AS
YOU'RE GOING THROUGH THE PROCESS
OF LEARNING AND WORKING WITH A
REGULATORY EXPERT OR A
TOXICOLOGY CONSULTANT YOU CAN
ALIGN WHAT THE MINIMUM PACKAGE
IS YOU WANT TO GET IN THE CLINIC
AND START WORKING BACKWARDS TO
LOOK AT THE ADDITIONAL ASSAY
GIVE THE MOST DECISION MAKING
CRITERIA FOR YOUR SPECIFIC
PROGRAM.
WHAT WHERE SOME THINGS YOU CAN
DO EARLY ON?
I THINK OF RESEARCH AS THE
SCREENING AND I REALIZE SMALL
ORGANIZATIONS OR ACADEMIA YOU
MAY ONLY HAVE A HANDFUL OF
COMPOUNDS TO DRAW FROM BUT
DOESN'T MEAN YOU CAN'T GO
THROUGH THE PROCESS OF THINKING
ABOUT WHICH ONES LOOK MORE LIKE
A DRUG.
I THINK YOU CAN DO COST
CONSCIOUS THINGS LIKE A TARGET
RISK ASSESSMENT.
THAT'S COMBING THROUGH THE
LITERATURE TO LOOK TO INCLUDE
FROM KNOCKOUT ANIMALS AND WHAT
DOES EXAGGERATED PHARMACOLOGY
LOOK LIKE IF I KNOCK DOWN THE
TARGET.
YOU CAN GET CLUES AROUND WHAT TO
ADDRESS.
IT'S IMPOSSIBLE TO PICK UP OFF
TARGET TOXICITY WHICH ARE MAJOR
DRIVERS FOR SMALL MOLECULE BUT
OTHERS WILL ADDRESS THOSE
PROACTIVELY.
THIS IS UNDERSTANDING YOUR
TARGET AND SOME LOW TARGET
EVALUATIONS ARE IMMUNOGENICITY
ASSESSMENTS LOOKING AT
RELATIONSHIPS WHETHER YOU USE A
COMPUTERIZED SYSTEM OR COMBING
THE LITERATURE ARE EFFECTIVE
TOOLS TO HELP IDENTIFY
PROBLEMATIC COMPOUNDS VERY EARLY
IN THE PROCESS AND EASY TO
ENGINEER AROUND WHEN YOU
IDENTIFY THEM WORKING WITH A
MEDICINAL CHEMIST YOU CAN PIVOT
WITHOUT LOSING A LOT OF
PHARMACOLOGY.
THERE'S OTHER STUDIES HERE ON
THE LEFT YOU CAN ALSO DO THAT
WE'LL HAVE TO BRIEFLY PASS OVER
TODAY BUT IT'S NOT -- IT'S ALSO
DONE IN A RISK APPROPRIATE
MANNER AS YOU TWO THROUGH THE
SCREENING FUNNEL, THE
REQUIREMENTS FOR THE AMOUNT OF
DRUG PRODUCT YOU NEED AND THE
COST ASSOCIATED WITH THEM RISE
SO YOU WANT TO GET RID OF THOSE
LOW HANGING FRUIT EARLY.
AS YOU PIVOT TO THE IN VIVO
STAGE OF DEVELOPMENT, WHAT ARE
SOME OF THE THINGS THAT ARE
REALLY GOOD TO DO VERY EARLY ON?
AS YOU MATURE IN TO RUNNING A
RODENT STUDY OR A LARGE ANIMAL
STUDY HOPEFULLY AFTER YOU HAVE
DONE A RODENT STUDY, SOME OF THE
EARLY NON-GLP RANGE FINDING
STUDIES ARE A TYPICAL 14-DAY
RANGE FINDING STUDY.
YOU CAN STAGGER THE INITIATION
OF DOSING STARTING WITH A LOW
DOSE.
SAY YOU KNOW LITTLE ABOUT YOUR
COMPOUND.
YOU MAY START AT DOSE LEVEL OF
10 MIGS PER DAY AND IF THINGS
LOOK GOOD IN THE STUDIES YOU MAY
STAGGER THE START OF A HIGH DOSE
GROUP.
DOSE FOR A COUPLE DAYS IF YOU
HAVEN'T IDENTIFIED INTOLERANCE
OR TOXICITY YOU MAY WANT TO PUSH
THE DOSES FURTHER.
AGAIN, A TOXICOLOGY STUDY THAT
DOES NOT IDENTIFY SAFETY
LIABILITIES IS NOT REALLY
DRIVING AND EDUCATING YOU AROUND
WHAT YOU NEED TO LOOK FOR.
AND HOPEFULLY YOU CAN IDENTIFY
WHAT YOUR KEY LIABILITIES MIGHT
BE WITH A COMPOUND AND USE THOSE
TO ROLLOVER ULTIMATELY TO YOUR
GLP TOXICOLOGY AND HERE I LIKE
TO DO A FOUR-WEEK STUDY BECAUSE
THIS WILL ENABLE UP TO A MONTH
CLINICAL DOSING FROM YOUR
COLLEAGUES WHICH ALLOWS THEM TO
RUN SAD AND MAD TYPE CLINICAL
STUDY DESIGNS IN BOTH THE RODENT
AND LARGE ANIMAL SPECIES
TYPICALLY.
AND THE LARGE ANIMAL SPECIES
DOES NOT NEED TO BE NON-HUMAN
PRIMATE.
IT COULD BE MINI PIG, DOG, NON
HUMAN PRIMATE OR ANY JUSTIFIED
SPECIES.
IDEALLY YOUR STUDY WOULD BE SET
UP TO IDENTIFY MOST IMPORTANTLY
A NO-OBSERVABLE ADVERSE EFFECT
LEVEL.
IF YOU CAN IDENTIFY LOW LEVELS
OF TOXICITY AT A MISS DOUGHED
AND MAXIMUM TOLERATED DOSE ARE
THE SPECTRUM WHERE YOU LEARN THE
MOST FROM THE STUDY DESIGNS.
NOW, OBVIOUSLY I'VE GLOSSED OVER
A LOT OF KEY DATA HERE AND
DETAILS AROUND THE STUDY DESIGNS
AND CONSIDERATIONS.
SO I REALLY ENCOURAGE YOU TO GO
TO ICH DOT ORG AND LOOK AT THE
GUIDANCE ALIGNED BY A GLOBAL
REGULATORY AUTHORITIES AROUND
THE PLAYBOOKS AND EXPECTATIONS
AROUND DEVELOPING THE
THERAPEUTICS.
FOR SMALL MOLECULES THAT'S
PROTEIN THERAPEUTICS HAS THEIR
OWN GUIDE AS WELL AS GENE
THERAPY.
THE GUIDANCE AROUND GENE THERAPY
IS GIST JUST STARTING TO EMERGE
SO LOOK AT THE FDA LONG-TERM
SAFETY GUIDANCE AS WELL.
I WANT TO HIGHLIGHT BRIEFLY
AROUND MONOCLONAL ANTIBODIES AND
PROTEINS.
SOME MAJOR DIFFERENCES IS THE
EMPHASIS ON EXAGGERATED
PHARMACOLOGY.
THE SPECIFICITY FOR THE
THERAPEUTICS ARE SO SPECIFIC
OVER TARGET TOXICITY IS
REFLECTED AROUND THE WAY WE
ASSESS THE PROGRAMS AND ASSETS.
KEEP IN MIND SOME OF THE BIG
DIFFERENCES WE HAVE WITH SMALL
MOLECULES IS THE LONG HALF LIFE
OF THE THERAPEUTICS.
IT'S NOT UNUSUAL TO RUN A
FOUR-WEEK GLP TOX STUDY TO
ENABLE CLINICAL DOSING FOLLOWED
BY A 13-WEEK RECOVERY NON-DOSING
PHASE BECAUSE THE LONG-ACTING
NATURE OF THE THERAPEUTICS ARE
SO LONG ACTING.
WE WANT TO MAKE SURE WE'RE
ASSESSING ALL THE POTENTIAL
SAFETY LIABILITIES OVER THE
DURATION OF EXPOSURE HERE.
AND THERE ARE ALSO VERY SPECIFIC
TISSUE CROSS REACTIVITY STUDY WE
CONDUCT TO MAKE SURE WE
UNDERSTAND WHAT THE FINDING
POTENTIAL IS BUT A LOT OF THESE
EFFECTS WE TYPICALLY LOOK FOR
WITH PROTEIN THERAPEUTICS OR
MONOCLONAL ANTIBODIES ARE REALLY
THE EFFECT ON THE IMMUNOGENICITY
AND HOW THE IMMUNE SYSTEM REACT
TO CLEAR THESE THERAPEUTICS
EARLY ON, WHICH MAY ACTUALLY
MINIMIZE THE EFFECTIVENESS OF
OUR TOXICOLOGY STUDY TO INFORM
CLINICAL IMPLICATIONS OR
ALTERNATIVELY THINKING HOW THE
IMMUNE SYSTEM MAY BE EITHER
EXPRESSED OR ACTIVATED DEPENDING
ON THE INTENDED PHARMACOLOGY OF
THE THERAPEUTIC.
TO BRIEFLY TALK ABOUT GENE
THERAPIES, AGAIN THESE ARE VERY
DIFFERENTIATED FROM SMALL
MOLECULES OR PROTEIN
THERAPEUTICS.
A LOT OF TIMES NOW IF WE'RE
LOOKING AT GENE THERAPIES WE
REALLY WANT TO UNDERSTAND THE
TROPISM AND BIO DISTRIBUTION
SPECIFICALLY WHAT TYPES OF CELLS
OR TISSUES DOES THE VIRUS
TRANSDUCE OR A LIPID NANO
PARTICLE, LET'S SAY.
WITHIN GENE THERAPIES THERE'S
DIFFERENT SUB HEADINGS AROUND
OLIGO NUCLEOTIDES AND THIS AREA
IS EXPLODING.
WE CAN'T POSSIBLY COVER ALL THE
BEST PRACTICES IN THIS SPACE
WITHOUT INTO SPECIFICS.
BUT AT A HIGH LEVEL WE REALLY
WANT TO UNDERSTAND THE BIO
DISTRIBUTION I MENTIONED.
THE PHARMACO KINETIC, PHARMACO
DYNAMIC PROFILE AROUND THE
VECTOR GENOMES OR DNA
DISTRIBUTION YOU'RE DELIVERING
WITH YOUR VECTOR LIPID NANO
PARTICLE AND THE PROTEIN
EXPRESSION YOU HAVE SECONDARY TO
THIS.
THEN AS WE TALKED ABOUT WITH
MONOCLONAL ANTIBODIES THE
IMMUNOGENICITY COMPONENT.
ARE THERE PREEXISTING ANTIBODIES
THAT MAY SUPPRESS THE EFFECT TO
MODEL THIS THERAPY IN YOUR
SPECIES.
AND THE IMMUNE RESPONSES.
REMEMBER IF YOU'RE DELIVERING A
VECTOR-BASED VIRAL-BASED GENE
DELIVER HADDY APPROACH YOUR
IMMUNE SYSTEM RECOGNIZES THIS
AND ACTIVELY THINKING IT'S UNDER
ATTACK AND WILL FIGHT BACK.
ARE THERE DOWN STREAM EFFECTS ON
CYTOKINE OR COMPLEMENT
ACTIVATION AND HOW DOES THAT FIT
IN WITH YOUR INTENDED
THERAPEUTIC DOSE.
THIS IS DIFFERENT THAN OTHER
MODALITIES WHERE YOU'RE DOSING
DAILY FOR A SMALL MOLECULE, SAY
WEEKLY OR BIWEEKLY FOR
THERAPEUTIC POTENTIAL OR LONGER
CADENCE.
AND THEN MAYBE A SINGLE DOSE
ONLY FOR THESE TYPES OF IND
ENABLING STUDIES.
IT'S REALLY IMPORTANT TO
UNDERSTAND WHAT YOUR LIABILITIES
ARE AND DEVELOP THE RIGHT
PACKAGE AND THIS IS WHERE IT'S
SO IMPORTANT TO WORK WITH A GOOD
REGULATORY OR TOXICOLOGY
CONSULTANT AS YOU'RE STARTING TO
THINK ABOUT THIS IF YOU'RE NEW
TO THE FIELD TO STEER IN AND
IT'S NOT A ONE-SIZE FITS ALL
TYPE OF SITUATION.
FINALLY, I WANTED TO OFFER SOME
PARTING THOUGHTS AROUND DRUG
SAFETY.
YOU HAVE TO UNDERSTAND UP FRONT
YOU CAN'T PREDICT EVERYTHING.
AS YOU'RE THINKING ABOUT YOUR
ASSETS EARLY ON, IT'S OKAY TO
BELIEVE AND ADVOCATE FOR YOUR
DRUGS.
THERE ARE THINGS YOU KNOW AND
THINGS YOU DON'T KNOW.
PART OF THE DRUG DEVELOPMENT
PROCESS AS MARRAH MENTIONED IS
TALKING TO INVESTORS TALKING TO
CLINICIANS AND KEY OPINION
LEADERS AND GET THEM EXCITED
ABOUT WHAT NOVEL THERAPEUTIC
OPTIONS YOU BRING TO DISEASES
POTENTIALLY WITH HIGH UNMET
NEED.
IT'S OKAY TO BE ENTHUSIASTIC
ABOUT YOUR DATA.
IT'S ALSO SOMETHING YOU NEED TO
APPRECIATE THERE ARE LIMITS TO
WHAT YOU KNOW AND DON'T KNOW
AROUND THE ROBUSTNESS OF THAT
DATA.
SO IT'S SO IMPORTANT TO BE
TRANSPARENT WITH PATIENT, YOUR
CLINICAL COLLEAGUES AND
CERTAINLY REGULATORS AROUND WHY
YOU BELIEVE A DRUG IS SAFE AND
EFFICACIOUS AND MAYBE AREAS YOU
DON'T KNOW OF UNCERTAINTY AND
HOW YOU PLAN ON ADDRESSING THAT
AROUND SAFETY MARGINS OR SAFETY
MARKERS YOU CAN FOLLOW IN
PATIENTS TO UNDERSTAND THIS.
I THINK IT'S OKAY TO BE PARANOID
AS YOU TWO THROUGH DEVELOPMENT.
THIS IS ACTUALLY A GOOD THING
AROUND UNDERSTANDING TYPICAL
ISSUES THAT MAY COME UP AND
YOU'LL HAVE SPURIOUS FINDINGS IN
SOME OF YOUR STUDIES OR DATA NOT
CONGRUENT WITH A -- THERE MAY BE
OPPOSING DATA SETS THAT SAY IN
ONE SPECIES IT MAY BE UNSAFE AND
ANOTHER SPECIES SAFE AND THEN
YOU HAVE TO GO THROUGH AND
FIGURE OUT WHICH IS THE RIGHT
ONE TO BELIEVE.
ALL THOSE ARE ACCESSIBLE AND
OKAY.
IT COMES BACK TO THE
TRANSPARENCY EFFECT.
YOU WANT TO AVOID BOX CHECKING.
IF YOU GO AND ASK PEOPLE WHAT
THEY DID FOR THEIR PROGRAMS, YOU
MAY GET STUDIES YOU ARE
ESSENTIALLY UNNECESSARY.
THIS IS A BIG CONSIDERATION WHEN
IN VIVO STUDIES COME INTO PLAY.
WHERE WE DON'T WANT TO BE
RUNNING UNNECESSARY IN VIVO
STUDIES THAT DON'T NECESSARILY
ADD VALUE.
THE EARLIEST YOU CAN PARTNER
WITH REGULATORY EXPERTS OR FOLKS
IN THE NON-CLINICAL SAFETY
SPACES, CONSULTANTS OR OTHERWISE
AND UNDERSTAND THE MINIMUM
PACKAGE THAT'S NECESSARY TO GET
INTO THE CLINIC, IT'S MOST COST
EFFECTIVE AND STREAMLINED AND
THEN START WORKING BACKWARDS TO
SAY, DOES THIS ADEQUATELY
ADDRESS MY SAFETY LIABILITIES
AND EFFICACY OBJECTIVES IN ORDER
TO TREAT THIS DISEASE?
THEN YOU START BUILDING OUT FROM
THERE.
I THINK ABOUT IT THIS WAY
BECAUSE IT MINIMIZES THE
UNNECESSARY STUDIES THAT DON'T
ULTIMATELY BRING VALUE TO YOUR
THERAPEUTIC.
AND AS YOU'LL HEAR FROM OTHERS
IN THE REGULATORY SPACE, PART OF
THIS DYNAMIC PROCESS WE HAVE IS
DISCUSSING WITH REGULATORS
AROUND HERE'S WHAT I BELIEVE IS
THE RIGHT PATH FORWARD AND THEY
KNOW THINGS FROM THEIR
EXPERIENCE AND SAY WE UNDERSTAND
THAT PERSPECTIVE BUT HAVE YOU
CONSIDERED THIS?
WE WOULD RECOMMEND YOU DO THIS
GOING FORWARD.
IT'S THE DYNAMIC PROCESS.
ALL THE CREDIT IN THE WORLD TO
THE FDA.
THEY'VE BEEN GREAT AROUND TRYING
TO IMPROVE THE COLLABORATIVE
DISCUSSION AROUND TRYING TO FIND
THE RIGHT PATH FORWARD FROM A
NON-CLINICAL SAFETY PERSPECTIVE
TO MINIMIZE RISK FOR PATIENTS.
AND THEN FINALLY'S OKAY TO APPLY
RISK IN A THOUGHTFUL, CALCULATED
MANNER.
I CAN TELL YOU HAVING ON EIGHT
MARKETED THERAPEUTICS RIGHT NOW,
THERE WAS A COMPELLING REASON TO
TERMINATE ALL OF THEM.
IT IS A VERY LONG, DRAWN OUT
PROCESS THAT INVOLVES A LOT OF
FOLKS ALONG THE WAY.
IT'S OKAY TO FIGHT AND CONVINCE
OTHERS TO GET THEM TO BELIEVE
WHAT YOU BELIEVE AND ADVOCATE
FOR PATIENTS AND WHAT YOU
BELIEVE IS AN EFFECTIVE THERAPY.
IT'S OKAY TO DO THIS.
JUST REMEMBER THAT SUCCESSFUL
PHARMACEUTICALS ARE
EXCEPTIONALLY RARE EVENTS AND
YOU NEED TO PUSH FORWARD AND
BELIEVE IN THEM.
AT THE SAME TIME ALWAYS
BALANCING THAT WITH PATIENT
SAFETY GOING FORWARD.
WITH THAT I'LL CONCLUDE MY
PRESENTATION AND TURN IT BACK
OVER TO MARRAH.
THANK YOU VERY MUCH.
>> THANK YOU, JEFF.
SO WE'LL MOVE INTO SESSION 1 AND
I WOULD LIKE TO OVER TO MY
COLLEAGUE, JOHN SHERIDAN.
>> THIS IS DRUG DEVICE
DEVELOPMENT PROCESS MODELS AND
METHODS CHIEF OF THE BRANCH OF
THE DIVISION OF LUNG DISEASES AT
NHLBI AND MY CO-MODERATOR IS
CHARLIE REN.
>> I'M FROM CARNEGIE MELON
UNIVERSITY.
>> THESE ARE WHAT MAY BE
EMPLOYED THROUGH THE
THERAPEUTICS FOR LUNG AND SLEEP
DISEASES AND DISORDERS.
SO WE HAVE FOUR EXCITING
PRESENTATIONS THAT WILL COVER
BOTH IN VITRO AND IN VIVO
MODELS.
THE FIRST SPEAKER -- NEXT SLIDE.
THE FIRST SPEAKER IS ALFRED
TAMAYO, A PRINCIPAL SCIENTIST
FROM CARBON BIO SCIENCES.
HE'LL BE FOLLOWED BY ERIN
HENNESSEY A Ph.D. CANDIDATE FROM
THE BOSTON UNIVERSITY SCHOOL OF
MEDICINE AND ERIN IS UNABLE TO
ATTEND LIVE SO HER PRESENTATION
WAS RE-RECORDED.
WE'LL NEXT HAVE A PRESENTATION
FROM KRISTIN BIRCSAK A PRINCIPAL
SCIENTIST AND THE FINAL
PRESENTATION IS FROM JOHN
ENGLEHARDT FROM THE UNIVERSITY
OF IOWA.
AND AS A REMINDER, WE'LL BE
HOLDING Q&A UNTIL THE PANEL
DISCUSSION AND TURG THE TALKS
YOU CAN ENTER ANY QUESTIONS YOU
HAVE USING THE Q&A FEATURE.
WITH THAT I'LL TURN IT OVER TO
OUR FIRST SPEAKER, ALFRED.
>> THANK YOU FOR THAT, DR
DR. SHERIDAN.
THANK YOU FOR THE MODERATORS FOR
CREATING THIS GREAT WORKSHOP AND
INVITING ME AND THE AMAZING
SPEAKERS IN THE GROUP.
I'LL SHARE A CASE STUDY FROM
ACADEMIC ROOTS TO PATIENTS WHO
NEED THEM.
IT'S A FEAT OF MONUMENTAL
PROPORTIONS AND WORKED WITH AN
INCREDIBLE GROUP.
I THINK WE HAVE A GOOD SHOT.
THAT'S BY FAR BEEN THE MOST
IMPORTANT LESSON TO DATE WITH
THE RIGHT PEOPLE AND MIND SET,
ANYTHING IS POSSIBLE.
WITH THE VIGNETTE I CAN OFFER
SNIPPETS OF THE MANY CHALLENGES
WE'VE FACED AND THOSE THAT ARE
SHORT COMES.
AS I SAID FROM THE START IT'S AN
UNFINISHED CASE STUDY SO I CAN'T
TELL YOU HOW IT ENDS BUT CAN
SHARE WHAT I'VE LEARNED ALONG
THE WAY FROM THE PERSPECTIVE OF
A CURRENT INDUSTRY SCIENTIST AND
FORMER ACADEMIC RESEARCHER.
A YEAR AND A HALF AT CARBON
MARKS MY FIRST LUNG FOCUSSED
INDICATION AND WORKED WITH A
COMPANY ATTEMPTING TO TACKLE
DRUG RESIST TACT -- RESISTANCE
OF THE LUNG AND AT THE MICROBES
AND NOT SO MUCH THE LUNG.
WE FACED CHALLENGES HOW TO MIMIC
THE RIGHT DELIVERY OF DRUG TO
HUMAN LUNGS AND WHAT MAY BE THE
TRANSLATIONAL MODEL AND FACED
CHALLENGES IN ACHIEVING POTENCY
AND ACCEPTED MODELS.
A SUBJECT THAT PERHAPS DESERVES
ITS OWN TALK.
AND I TOOK A POSITION AT
ANALYTICA AND IT WAS A STORIED
COMPANY OF A FEW HUNDRED PEOPLE.
AND THE MANUFACTURING FACILITY
IN THE QC DEPARTMENT AND WORKED
WITH THE THERAPEUTIC ON CMS FOR
CHEMISTRY, MANUFACTURING AND
CONTROLS.
AS AN ACADEMIC INITIALLY
INDUSTRY SCIENCE I HAD NEVER
HEARD THE TERM BUT IF YOU WANT
TO BRING THE DRUG TO THE CLINIC
IT'S ADVISABLE TO THINK OF
PRACTICES AND GUIDELINES JEFF
TOUCHED UPON.
I'LL TOUCH ON THIS NOW AND BEEN
DURING MY TALK.
WHEN I FIRST SAW CARBON IT WAS
PRIMARILY THROUGH THE LENS OF MY
EXPERIENCE AT ANALYTICA AND
TECHNOLOGY BY A CO-FOUNDER BUT
THAT'S A STORY BY ANOTHER TIME.
CARBON IS TRYING TO CORRECT
CYSTIC FIBROSIS.
THERE'S NO APPROVED GENE
THERAPIES OF ANY KIND FOR CYSTIC
FIBROSIS AND WHILE IT'S
EXHILARATING IF YOU'RE NOT
TERRIFIED YOU PROBABLY HAVEN'T
THOUGHT IT THROUGH.
CYSTIC FIBROSIS IS A
LIFE-THREATENING INHERITED
DISEASE WITH HIGH MORBIDITY AND
MORTALITY AND AVERAGE AGE OF
DEATH OF 40 YEARS OLD.
WHILE THERE'S SMALL MOLECULE
DRUGS AVAILABLE NOT ALL PATIENTS
CAN USE THEM.
A CRITICAL SUBSET OF CF HAVE
INTOLERANCE OR NON COMPLIANCE
AND WILL TARGET 10,000 PATIENTS
NOT CURRENTLY ELIGIBLE FOR
STANDARD OF CARE DRUGS.
CARBON PLANS TO REFER TO AN
APPROACH THAT DELIVERS GENETIC
INFORMATION TO A PATIENT'S
CELLS.
IF THE PATIENT'S DISEASE IS
CAUSED BY MUTATION THAT RESULTS
IN THE LACK OF FUNCTIONAL
PROTEIN AS IS THE CASE FOR CF,
THEN DELIVERING A NORMAL COPY OF
THE GENE COULD HAVE THERAPEUTIC
OR CURATIVE EFFECTS.
THIS APPROACH CAN COME IN
SEVERAL MODALITIES THROUGH LIPID
NANO PARTICLES OR VIRAL VECTORS.
VIRAL VECTORS ARE VIRUSES
ENGINEERED TO DELIVER PAY LOADS
WITHOUT REPLICATING.
AMONG THE MOST COMMON EMPLOYED
ARE AAV AND LINDSEY VIRUS
HOWEVER, VIRAL VECTORS CAN COME
WITH SIGNIFICANT RISK AND
LIMITATIONS INCLUDING TISSUE OFF
TARGET EFFECTS AND LIMITED PAY
LOAD AND NEUTRALIZING OR
DANGEROUS IMMUNOGENIC RESPONSES.
CARBON TECHNOLOGY SEEKS TO PUR
PASS THE LIMITATION OF THE
CURRENT STATE OF TECHNOLOGY BY
TAKING ADVANTAGE OF THE
UNEXPLORED LANDSCAPE AND THEY
HOLD THE PROMISE OF GREATER --
SPECIFICITY AND GREATER GENETIC
PAY LOAD.
IT BUILDS ON IMPROVED ASSETS OF
GENE MODALITIES.
FOR EXAMPLE, WE CAN FIND WELL
VETTED MANUFACTURING SAFETY
PRACTICES TO OUR PLATFORM WHICH
MAY INTERN DELIVER MEDICINES TO
PATIENTS IN NEED.
AND IT HAS ITS ROOTS IN THE
PIONEERING WORK OF OUR
CO-FOUNDERS WHO YOU'LL HEAR TALK
SOON, DR. ENGLEHARDT AND DR. JAN
AND DELIVER A NORMAL COPY OF THE
GENE.
BEING ENGINEERED BY EVOLUTION
FOR SPECIFICITY TO THE HUMAN
LUNG IT STANDS POISED TO MAKE
ITS MARK ON GENE THERAPY.
CARBON IS THE ONLY ONE THAT
DELIVERS THE FULL LENGTH BUT
BEING SUITED TO YOUR TARGET CAN
COME WITH THE INABILITY TO USE
SMALL PRODENTS.
-- RODENTS.
AT CARBON OUR GOAL IS DELIVER
AND THE LUNG IS A MARVELOUS
DIVERSE ELEMENT AND THIS IS
COMMON KNOWLEDGE TO THOSE IN THE
FILED BUT THE FIRST TIME I
LOOKED AT THIS PICTURE FILLED ME
WITH WONDER AND ANGST, WHERE
SHOULD WE DELIVER THE CELL OR
HAVE AMELIORATED PROPERTIES?
CAN WE HAVE DELETERIOUS EFFECTS
TO THE WRONG CELLS OR
CONCENTRATIONS?
THESE ARE THE CHALLENGES AND
CONSIDERATIONS WE MUST TRY TO
ADDRESS AS WE CONTINUE TO BRING
OUR MEDICINES TO CLIN INNING.
-- CLINIC.
SMALL RODENTS AND RATS ARE USED
TO ASSESS EFFICACY.
AND THERE'S CHALLENGES BEHIND.
NEB YOU'LLULIZING THE VECTOR
AND HOW CAN WE MAKE SURE WE'RE
MAKING THE SAFEST AND MOST
EFFICACIOUS DRUGS POSSIBLE
BEFORE MOVING INTO MORE COSTLY
AND COMPLICATED MODELS SUCH AS
LARGE ANIMAL STUDIES AND LOOK AT
EXISTING IN VITRO MODELS WE MAY
LEVERAGE.
AND WE HAVE STEM LIKE CELLS WILL
DIFFERENTIATE INTO DIFFERENT
CELL TYPE WHEN IT'S CLOSE TO AIR
ON ONE SIDE.
AS IT WOULD IN THE AIRWAY.
A WELL DOCUMENTED TECHNIQUE
COMMONLY REFERRED TO AS
INTERFACE OR ALI CULTURES, THIS
COULD BE AP CAPTURE AND IDENTIFY
PROTEIN MARKERS.
THE IMAGES WERE PROVIDED BY
PARTNERS AT THE CYSTIC FIBROSIS
FOUNDATION.
AS AMAZING AS THIS IS IT
PROVIDED ANOTHER MOMENT OF
ANGST.
THROUGH THE CMC LENS
CONSIDERATIONS AROSE IN THE
PROJECT.
WELL THE WORK FLOWS BE ROBUST
AND REPRODUCIBLE ENOUGH TO GUIDE
OUR PROCESSING?
CAN THEY BE ADAPTED TO PERFORM
AT THE LEVEL REQUIRED TO SUPPORT
PHASE 1 TESTING?
CAN WE RELY ON SUPPLY OF
RE-AGENTS SUCH AS TESTING GNP
LOSS.
MOST THE WORK DONE IN THE SYSTEM
WAS WITH CELLS WHICH THEN GIVE
RISE TO THE CONCERN OF
VULNERABILITY AND AVAILABILITY.
HERE AGAIN I MUST GIVE CREDIT TO
A CO-FOUNDER AND THE CMTR CAN
RECOVER FUNCTION IN THE CELL
LINE DERIVED FROM THE
PARTICIPANT LUNG.
AT CARBON WE HAVEN'T BEEN ABLE
TO REPRODUCE THIS AND THIS
BRINGS ME TO THE NEXT ATTRIBUTE.
THE ABILITY TO RECAPITULATE LUNG
CELL ACTIVITY.
PATIENTS WITH CF LACK FUNCTIONAL
CTR.
CONSEQUENTLY THERE'S NO EFFECT
ON PATIENT CELLS.
THIS IS FUNCTION AND RECOVERY IS
WELL DOCUMENTED IN THE ALL RIGHT
AND CAN BE MODELLED BY ADAPTING
THE TECHNIQUE TO THE DEVICE AND
THE NAME FOR THE CHAMBER.
IT ALLOWS US TO DIRECT IONS IN
THE PRESENCE OR ABSENCE OF THE
THERAPEUTIC.
THE ABILITY TO ACCOMPLISH THIS
USING ESTABLISHED HUMAN CELL
LINE SHOULD NOT BE UNDER STATED.
THIS ALLOWS US TO CREATE LINES
AND CELL BANKS AS NEEDED TO
IMPROVE ROBUST REPRODUCIBLE
RESULTS.
FORTUNATELY, GENETICALLY MODE
MODIFIED CELL LINES TO
CAPITULATE THE TARGET.
AT CARBON WE HAVE TAKEN THE NEXT
STEP AND SHOWN AND THE CELL LINE
IS RESPONSIVE TO STANDARD OF
CARE THERAPEUTICS AND I'LL WALK
THROUGH THE DATA FOR THE SAKE OF
THOSE NOT DOMAIN EXPERTS.
THE Y AXIS MEASURES THE
MAGNITUDE OF THE SHORT CIRCUIT
CURRENT SEPARATE THE BY LAYER OF
LUNG CELLS.
THE GRAY LINE REPRESENT
REPLICATES OF CELLS.
WHEN NO CELLS ARE REPRESENTED
WITH THE ACTIVITY THEY DO NOT
STOP.
THE BLUE LINES REPRESENT THE
CELL LINE TREATED WITH APPROVED
DRUGS.
THOSE CELLS CLEARLY RESPOND TO
THE STIMULUS AND RETURN TO
BASELINE WHEN SPECIFIC
INHIBITERS RETURN.
I'M HAPPY TO REPORT WE AT CARBON
CAN NOW GENERATE OUR OWN GENETIC
MEDICINE FOR CYSTIC FIBROSIS
LEVERAGING THE TECHNIQUE WE
DEMONSTRATED OUR VECTOR CAN
TARGET A VARIETY OF AIRWAY CELL
POPULATIONS RELEVANT FOR DISEASE
POPULATION AND DEMONSTRATE THE
RECOVERY OF ACTIVITY COMPARABLE.
NATURE HAS MADE THE HUMAN CAPSID
HIGHLY SPECIFIC TO THE HUMAN AUR
WAY.
AN IDEAL AND UNPRECEDENTED
CANDIDATE FOR A GENE THERAPY TO
TREAT LUNG CASES AND THIS
ESTABLISHES SAFETY AND EFFICACY
IN NON-HUMAN ANIMAL MODELS.
WE CAN LEVERAGE A WELL VALIDATED
IN VITRO SYSTEM TO DEMONSTRATE
DRUG EFFICACY.
A MAJOR CHALLENGE ON OUR PATH TO
IND AND ULTIMATELY TO THE CLINIC
IS ESTABLISHING A PSEUDO TOX KOL
BY MODEL TO ENSURE THE SAFETY OF
OUR DRUGS IN PATIENT.
TO ACCOMPLISH THIS WE'LL ATTEMPT
TO ADMINISTER THE CTG001 TO
NONHUMAN PRIMATES AND I'D LIKE
TO TAKE A MOMENT TO THANK OUR
PARTNERS.
>> THANK YOU.
NEXT WE'LL HAVE THE PRESENTATION
FROM ERIN, PLEASE.
>> I'M ERIN HENNESSEY AT BOSTON
UNIVERSITY AND WE'RE THINKING
HOW TO BEST SERVE PATIENTS WITH
UNMET NEEDS AND RARE DISEASE
POPULATIONS WHERE WE CANNOT DO
POWERED CLINICAL TRIALS.
WE THINK ABOUT INHERENTLY
VULNERABLE POPULATIONS LIKE KIDS
WITH PEDIATRIC DISEASES AND
THINK ABOUT PATIENTS WITH SEVERE
DISEASE AND SPECIFICALLY WHEN
THINKING ABOUT LUNG DISEASE,
PATIENTS FOR WHOM A BIOPSY OR
TISSUE COLLECTION WOULD BE
HARMFUL OR DANGEROUS.
THE QUESTION REMAINS IS HOW CAN
WE STUDY DISEASES IN THE
VULNERABLE POPULATIONS?
WE LOOK TO INDUCED HEMATOPOIETIC
STEM CELLS OR IPSCs AND TAKE THE
FROM A PUNCH AND TURN BACK THE
CLOCK TO REPROGRAM THEM TO A
STATE MEANING THEY THEN HAVE THE
POTENTIAL TO BECOME PRETTY MUCH
ANY CELL TYPE YOU CAN THINK OF.
AND WHERE WE ADD A TIME SERIES
OF GROWTH FACTORS WE CAN LED
THEM TO BE OUR CELLS OF INTEREST
AND WE CAN EASILY TAKE CELLS
FROM ANY DONOR AND TURN THEM
INTO IPSC CELLS AND CAN TURN
BACK TIME TO A TIME BEFORE
DISEASE PROGRESS AND CAN HONE IN
AND IDENTIFY WHAT AND WHEN AND
WHERE THINGS WENT WRONG.
THERE'S VALUABLE INFORMATION
STORES IN THE CELLS.
I'LL USE THIS TO STUDY DISEASE
WITH UNMET NEEDS AND CONCENTRATE
ON CHLID BECAUSE THAT'S WHAT MY
Ph.D. REASON IS ON BUT I ALSO
THINK IT FITS THE BILL AND IS A
RARE DISEASE THAT AFFECTS 1 IN
10,000 BIRTHS IN THE U.S. AND
AFFECTS A PEDIATRIC POPULATION.
FROM THE MAJORITY OF CASES ARE
CAUSED BY MUTATIONS IN THE EBCA3
GENE WHOSE ASSOCIATED PROTEIN IS
INSTRUMENTAL IN THE PULMONARY
SURFACTANT SO IT LEADS TO A
SURFACTANT SUFFICIENCY THOUGHT
TO BE DRIVING A DISEASE AND
KNOWN DRIVER OF THE DISEASE AND
HAVE EVIDENCE TO SUGGEST THERE'S
MORE TO IT THAN THAT I'M SHOWING
HISTOPATHOLOGY AND WE SEE THESE
ORGANELLES AND THEY'RE
SURFACTANT PRODUCTION TAKES
PLACE AND HAVE MORPHOLOGY OF A
FINGERPRINT OR RINGS OF I ATREE.
ON THE RIGHT I'M SHOWING
PATHOLOGY FROM A PATIENT WITH
ABC3 MUTATION AND THEAL --
ALVEOLAR SPACE HAVE LOST THE AND
IT'S ASSOCIATED WITH HIGH
MORBIDITY AND MORTALITY BECAUSE
THERE'S NO REAL TREATMENTS THAT
ADDRESS IT.
CURRENTLY IT'S MANAGED WITH
THINGS LIKE IMMUNOSUPPRESSANTS
AND HIYDROXYCHLOROQUINE AND
THERE'S AN URGENT NEED TO STUDY
THE DISEASE FOR TREATMENT.
WE COULD USE PRIMARY PATIENT
CELLS BUT THEY ARE DIFFICULT TO
ACQUIRE AND WE WANT TO STUDY THE
INCEPTION OF THE DISEASE.
WHEN WE GET PRIMARY CELLS
THEY'RE OFTEN FROM A DONOR WHOSE
DISEASE HAS ALREADY PROGRESSED
SO YOU'RE NOT ABLE TO STUDY THE
START OF THE DISEASE.
FOR THESE REASONS WE CHOOSE TO
USE IPSC CELLS AND HOW DO WE GET
TO I22s.
HERE'S IMAGES OF THE MUTATION.
THE SCAN ON THE LEFT SHOWS
PULMONARY REMODELLING AND
THICKENING AND THE BLACK ARROW
POINTS.
WE TOOK A BLOOD DRAW AND ISOLATE
THE CELLS WE NEEDED ANDRY
CULTURED TO BECOME IPSC AND
HERE'S THE CELLS.
WE KNOW THEY'RE IPSCs.
AND FOR THE PROCESS OF
DIFFERENTIATION WE TURN THEM
INTO AIA2s AND THE RED IS A
REPORTER KNOCKED IN AND HAS
ACCESS LIKE A WAY TO PURIFY THE
CELLS AND WE KNOW THEY'RE
SCOMBREFG THE PROGRAM-- EXPRESS
HOW DO WE STUDY THE MUTATION?
THE GRAD STUDENT BEFORE ME
APPROACHED THE QUESTION BY
FUSING GFP THROUGH THE
ENDOGENOUS LOCUS TO RAISE THE
PROTEIN.
BEFORE SHE DID THIS IN ANY CELLS
FROM THE DONORS HE FIRST
PERFORMED THE EXPERIMENT IN THE
CELL LINES WE HAVE IN OUR CENTER
FROM A HEALTHY DONOR.
BECAUSE ABCA3 GOES TO THE
LIMITING MEMBRANE WHAT WE EXPECT
TO SEE ARE GREEN CIRCLES AND
WHEN WE DIFFERENTIATE THE CELLS
AND LOOK AT THEM THAT'S WHAT WE
SEE.
HERE I'M SHOWING YOU WHAT WE
CALL AN ALVEOLAR SPHERE THAT
HAVE GROWN TOGETHER AND WHAT'S
COOL IS THEY'RE POLARIZED LIKE A
LUNG AND WE KNOW THE CELLS ARE
ACTUALLY PUMPING SURFACTANT INTO
THE MIDDLE OF THE OPEN SPACE
ACTING LIKE THE LUNG LUMEN.
BECAUSE IT'S FROM A HEALTHY
DONOR WE SEE NICE JUICY CIRCLES
WORKING HARD TO MAKE THE
SURFACTANT.
HOW MIGHT THE IMAGE CHANGE IF
THE IG2s STUDY THIS AND WE TOOK
OUR HEALTHY DONOR LINE AND
FUSION PROTEIN AND KNOCKED IN A
HOMOZYGOUS WAY THE MUTATION.
IN THE MIDDLE WE SHOW IG2s WITH
A TYPE 1 MUTATION AND THEY'RE
KNOWN TO DISRUPT THE PRACTICING
OF THE PROTEIN.
AS EXPECTED HERE, THE ABC IS
MORE DIFFUSED AND NOT GETTING
PROPERLY TRAFFICKED.
ON THE RIGHT I'M SHOWING CELLS
WITH HOMOZYGOUS MUTATION WITH
THE FUNCTION OF THE ABCA3
PROTEIN AND WE SEE ABC3 LOCALIZE
TO NORC BODIES AND THEY'RE
SMALLER AND MORE FROM THE
EXPERIMENTS FROM A HEALTHY DONOR
WE CAN DO THE SAME TYPES OF
EXPERIMENTS FROM OUR ILD DONOR.
WHAT WE DO IS CORRECT THE ABC3
MUTATION THEY HAVE, WHICH IS
EASIER TO DO IN A PETRI DISH
THAN A PERSON AND WE END UP WITH
THE WILD TYPE CONTROL WITH ALL
THE DONOR'S INFORMATION WITH
ONLY ONE ABCA3 VARIANT CHANGE.
IN ADDITION TO MEASURING ANOTHER
BODY SIZE AND SURFACTANT
PRODUCTION WE HAVE UNBIASSED
WAYS TO ASK THE CELLS WHAT'S
GOING ON AND WE DO THIS THROUGH
OUR SEQUENCING.
I'M SHOWING DATA FROM THAT HERE.
THIS IS INFORMATION THAT YOU
MIGHT FIND IN THE DISEASE AND A
WAY TO LOOK AT THE PATHWAYS THAT
HAVE BEEN DISRUPTED OR PERTURBED
AND FURTHER DRIVING THE DISEASE.
SO SOME OF THESE PATHWAYS PLAY
BE FIXABLE, IE DRUGGABLE.
FIRST I WANT TO DRAW YOUR
ATTENTION TO THE UPREGULATED
PATHWAYS IN THE MUTANT CELLS.
HERE WE'RE SEEING THINGS LIKE
INTERFERON RESPONSES, APOPTOSIS
AND THERE MAY BE MORE HAPPENING
THAN JUST THE SURFACTANT
DEFICIENCY ALONE.
WE THINK THE UP REGULATION OF
INFLAMMATORY PATHWAYS MAY BE THE
RESULT OF ONE OF TWO THINGS, THE
MUTANT PROTEIN IS ACTING IN A
WAY TO CAUSE THE REGULATIONS IN
A MECHANISM OR B, THE
INFLAMMA
INFLAMMATION ARE UNHAPPY CELLS
AND SOMETHING WE'RE WORKING TO
UNDERSTAND.
SOMETHING WE KNOW ABOUT THE A2
CELLS THE MAJOR PRODUCTION IS
THE SURFACTANT PRODUCTION AND
PLAY A ROLE AS A PROGENITOR CELL
AND HOW TO REPOPULATE THE
ALVEOLI.
AND THE PATHWAYS INDICATE TO US
THAT WITH THE DISEASE THE CELLS
MAY BE LOSING SOME OF THEIR
PROBETWEEN FOR POTENTIAL.
-- PROGENITOR POTENTIAL.
THE TWO CONCEPTS WE OFTEN TALK
ABOUT IN DEVELOPMENTAL BIOLOGY
IS NECESSARY AND SUFFICIENT.
IF AN EVENT IS NECESSARY WE KNOW
IT IS REQUIRED IN ORDER FOR THE
OUTCOME TO OCCUR.
FOR EXAMPLE, WITH KNOW IF WE
TAKE IG2s FROM A DONOR FROM THE
ABCA3 MUTATION WITH ONLY ONE
NUCLEOTIDE IS ENOUGH TO RESTORE
THE FUNCTION OF THE CELLS.
IN OTHER WORDS EVEN WITH ALL
THE INFORMATION THE PATIENT HAS
THERE'S ONE MUTATION NECESSARY
TO CAUSE ALL -- AND THE EVENT
ALONE IS ENOUGH TO GUARANTEE THE
OUTCOME.
FOR EXAMPLE, IF WE TAKE OUR IN
HOUSE IPSC LINE FROM OUR HEALTHY
DONOR WITH ALL THEIR GENETIC
INFORMATION WE HAVE END UP WITH
REDUCED SURFACTANT PRODUCTION
INDICATING ONE MUTATION IS
SUFFICIENT TO CAUSE THE DISEASE.
SO IN DOING DISEASE RESEARCH
THIS IS A POWERFUL INFORMATION
TO HAVE AND ABLE TO UNDERSTAND
IT BECAUSE YOU HAVE OUR IPSC
CELL MODEL.
BRIEFLY I'LL TALK ABOUT THE MEAT
OF MY Ph.D. PROJECT AND WANT TO
DEVELOP A THERAPEUTIC FOR ABCA3
AND THINK GENE THERAPY COULD BE
A GOOD AVENUE TO EXPLORE.
I KNOW I REFERENCED THE FACT WE
THINK IT'S A MUTATION FOR GAIN
OF FUNCTION BUT THERE'S PLENTY
OF MUTATIONS WE KNOW OF AND
DELETIONS AND PREMATURE STOPS
THAT ARE LOSS OF FUNCTION.
SO ONE OF THE PILLARS OF A GOOD
FWE
GENE THERAPY IS EFFICIENT AT
GENE TRANSFER.
I'VE BEEN EXPLORING VIRAL
OPTIONS FOR GENE THERAPY.
I'M SHOWING THE ACTUAL
TECHNIQUE.
THE CELLS TYPICALLY GROW -- LIKE
I SHOWED BEFORE IN STEROIDS IN
3-D MAKER GELS BUT CAN GROW THEM
IN AIR LIQUID INTERFACE, ALI,
WHERE THEY'RE IN A MONOLAYER ON
A TRANS MEMBRANE SO THE BASAL
LATERAL SIDE ARE EXPOSED AND THE
OTHER EXPOSED TO AIR.
AND THEY MAY EXIST IN VIVO.
THERE'S A MORE RELEVANT CULTURE
SYSTEM.
TO TEST VIRAL EFFICIENCIES AND
IN TERMS OF VIRUSES I TRIED WERE
LENTI VIRUSES IN COLLABORATION
WITH A GROUP AT UNIVERSITY OF
IOWA.
WE TRIED A FEW PSEUDO TYPES OF
LENTI VIRUSES WITH THE HOPES
SOME WOULD BE MORE EFFICIENCY
THAN OTHERS.
AND THE GENE I'M TRANSFERRING
ARE GFP.
WE FOUND SOME PSEUDO KINDS BUT
VERY LITTLE.
LOOKING TO THE GRAPH TO THE
RIGHT AND THE GENE TRANSFER WAS
LESS THAN 5%.
THOUGH WE DON'T KNOW EXACTLY HOW
EFFICIENT A VIRUS NEEDS TO BE IN
ORDER FOR THE GENE THERAPY AND
I'M EXPLORING GENE THERAPY IN
THE EXPERIMENT I'M TESTING AN
TYPE CREATED BY SARAH WOOTEN'S
GROUP SPECIFICALLY TROPIC FOR
TYPE 2 CELLS AND ABLE TO GET UP
TO 80% TRANSDUCTION THERAPY IN
THE CELLS IN VITRO AND IN
CULTURE AND IN VIVO.
AND IT'S BEEN PROVEN TO BE AN
EFFICIENT VIRUS MORE SO THAN THE
LENTI VIRUSES OR ONLY ABLE TO
GET 5% EFFICIENCY.
THE PROBLEM IS THE CARGO
CAPACITY OR AAD IS SMALLER THAN
THE SIZE OF THE GENE SO WHAT I'M
CHOOSING TO DO IS TO DELIVER THE
HALF SEPARATELY WHICH IS WHY IN
THE EXPERIMENT I'M SHOWING HERE
I'M TESTING THE DUAL DELIVERY
MODEL AND SEE THEY'RE ABLE TO BE
TRANSDUCED WITH HIGH EFFICIENCY.
THESE LENTI VIRUSES AND SYSTEMS
ARE A FEW OF THE THERAPEUTIC
OPTIONS WE ARE INVESTIGATING FOR
ABCA3 THERAPIES RIGHT NOW.
IN THIS TALK, I HOPE I HAVE
IMPRESSED UPON YOU THE UTILITY
OF IPSCs AS A MODEL FOR
VULNERABLE DISEASE POPULATION.
SOME TAKEAWAYS I HOPE ARE IPSC
CELLS ARE PATIENT SPECIFIC.
WHEN YOU TAKE THEM FROM A DONOR
NOT ONLY WILL THEY KWON TAIN
YOUR MUTATION OF INTEREST AND
THE GENETIC INFORMATION.
NUMBER TWO, THEY ARE EXPANDABLE
IN CULTURE.
THEY'RE RENEWABLE AND NEARLY
INEXHAUSTIBLE WHICH IS A GREAT
RESOURCE TO HAVE AND FREEZE THEM
AND RETURN TO THEM YEARS LATER.
NUMBER THREE, THEY'RE A
REDUCTIONIST MODEL.
THIS IS BOTH A PRO AND CON
DEPENDING ON HOW YOU LOOK AT IT
AND WHAT YOUR NEEDS ARE.
FOR MY PURPOSES IT'S BEEN
HELPFUL TO BE ABLE TO STUDY THE
DISEASE MANIFESTATIONS IN AD2
ALONE BEFORE MOVING TO THE
GREATER LUNG.
FOUR, THEIR EDITABLE AND CORRECT
THE PATIENT MUTATION OR KNOCK-IN
MUTATION WHICH GIVES US THE
POWER OF CONTROLS.
AND NUMBER 5, DRUGGABLE AND USED
TO EXPLORE THERAPEUTIC OPTIONS
LIKE THE GENE THERAPY I SHOWED
YOU.
OKAY.
THANK YOU ALL VERY MUCH FOR
LISTENING.
I'M NOT ABLE TO BE LIVE IN THE
WORKSHOP THIS MORNING BUT PLEASE
DON'T HESITATE TO REACH OUT WITH
ANY QUESTIONS OR COMMENTS YOU
MAY HAVE.
THANK YOU.
>> OKAY.
THANK YOU.
SO OUR NEXT TALK IS BY
DR. BIRCSAK FROM MIMETAS.
>> THANK YOU FOR THE
INTRODUCTION.
I WANT TO THANK THE ORGANIZERS
FOR THE INVITATION TO PRESENT
TODAY.
I'M EXCITE TO SHARE THE LATEST
MEMETICS AND ORGANOID CHIP
MODELS FOR MIMICKING DISEASE
PROCESS.
HERE'S AN OVERVIEW OF OUR
PRESENTATION.
FIRST WE'LL START OFF WITH AN
INTRODUCTION TO MIMETAS AND MOVE
ON TO THE ORGAN CHIP SYSTEMS.
I WANT TO THANK ANTWAN IN
ADVANCE.
I HAVE MULTIPLE TRANSITIONS IN
THE SLIDES SO THANK YOU AND I'LL
BE KEEPING YOU ON YOUR TOES, I
THINK.
MIMETAS IS A COMPANY WITH
PROVIDES MODELS AND ORGANS ON A
CHIP.
A MORE COMPLEX IN VITRO MODELS
THAT AID TO GENERATE CRITICAL
INFORMATION AND IT'S A GLOBAL
COMPANY.
WE ARE HEADQUARTERS IN THE
NETHERLANDS AND HAVE OFFICES IN
JAPAN AS WELL AS IN THE UNITED
STATES.
I'M BASED IN OUR OFFICE IN
MARYLAND WHERE WE HAVE A SMALL
RESEARCH AND DEVELOPMENT TEAM.
OUR ORGAN ON CHIP SYSTEMS COME
WITH KEY BUILDING BLOCKS THAT
ARE IMPORTANT FOR MODELLING
TISSUE.
SO WE CAN MODEL EPITHELIUM, THE
CONNECTIVE TISSUE, VASCULATURE,
THE IMMUNE SYSTEM.
WE KNOW THEY'RE ALL IMPORTANT
PARTS AND IT'S IMPORTANT TO KEEP
IN MIND WE CAN INCORPORATE ALL
OF THEM BUT IT DEPENDS ON YOUR
RESEARCH QUESTION WHETHER
NECESSARILY SHOULD INCORPORATE
ALL THOSE COMPONENTS INTO YOUR
MICROPHYSIOLOGICAL SYSTEM.
AND I THINK WHAT SETS US A PART
FROM OTHER MICROPHYSIOLOGICAL
SYSTEMS IS THE FACT WE'RE A
SCREENABLE PLATFORM.
WE CAN MODEL THESE TISSUES EIGHT
SIGNIFICANT SCALE AND WHAT
ENABLES US TO DO THAT IS THE
FACT THAT CHIPS ARE CONTAINED
WITHIN A 384 FOOTPRINT.
WE'RE FITTING ON STANDARD
LABORATORY MICROSCOPES, PLATE
READERS, HIGH CONTENT
MICROSCOPES, LIQUID HANDLERS YOU
CAN SEE ON THE RIGHT SIDE AND
THE PLATFORM IS CALLED THE
ORGANO PLATE.
WE'LL GO INTO MORE DETAIL SOON
ABOUT THAT.
BUT THE FACT IT'S IN THE
FOOTPRINT MEANS WE CAN USE AUTO
MATED LIQUID HANDLING AND THIS
ENABLES US TO BE ABLE TO CULTURE
TENS OF PLATES AT A TIME AND WIN
ONE PLATE WE HAVE ANYWHERE FROM
40 TO 96 INDIVIDUAL TISSUES OR
REPLICATES YOU CAN IMAGINE.
SO IT WOULD BE FEASIBLE AND
WE'VE DONE THIS BEFORE TO SCREEN
THOUSANDS OF YOUR CHIPS TO
POTENTIALLY FIND NOVEL
COMPOUNDS.
HERE I'LL SHOW YOU A VIDEO TO
GIVE YOU AN IDEA HOW IT PLATES.
THE BOTTOM HAS MICROSCOPE
QUALITY GLASS AND SEE THE THREE
CHANNELS IN PARALLEL.
WE CAN ADD IN OUR EXTRA CELLULAR
MATRIX GEL AND NO BARRIERS THAT
SEPARATE THE CHANNEL.
WE HAVE THIS PHASED GUIDE AND
CAPILLARY PRESSURE BARRIER THAT
PREVENTS THE EXTRA CELLULAR
MATRIX FROM SPILLING OVER.
ONCE THAT SOLIDIFIED WE CAN ADD
CELLS AND MEDIA TO THE ADJACENT
PERFUSION OR MEDIA CHANNELS AND
WE CAN ACHIEVE PERFUSION BY
PLACING THE PLATE ON A ROCKER
SYSTEM DIRECTLY WITHIN THE
INCUBATOR AND STACK MULTIPLE
PLATES ON THE SYSTEM.
WHAT WE FIND OVER TIME IS THAT
WHEN WE HAVE THE CELLS IN THE
PROFUSION CHANNEL THEY'LL
PROLIFERATE AND FORM THIS 3-D
STRUCTURE IN THIS CASE MIMICKING
A BLOOD VESSEL.
THAT'S A BIT ON THE PLATFORM IN
GENERAL.
NOW I'D LIKE TO GO INTO MORE
DETAIL IN OUR AIRWAY ORGANOID
CHIP SYSTEM.
WE'RE FOCUSSING PRIMARILY ON
THE LUNG.
WE CAN MODEL DIFFERENT DISEASE
PLATFORM DISEASES WITH AN
INTERNAL TRIGGER, BY CELLS THAT
EXPRESS MAYBE A CERTAIN DISEASE
MUTATION OR EXTERNAL TRIGGER BY
APPLYING INFECTIOUS COMPONENTS
LIKE VIRUSES AND THINGS LIKE
THAT.
AND WE'RE ALSO CAPABLE OF HAVING
MULTIPLE READOUTS WITHIN ONE
CHIP COLLECTING A LOT OF
DIFFERENT DATA.
SO THE BOTTOM MADE OF THE
MICROSCOPE QUALITY GLAD WE'RE
ABLE TO PERFORM IMAGING AND
CAPTURING REALLY IN SITU THE 3-D
STRUCTURE OF THE TISSUE.
CAN TO ELECTRICAL SENSING,
EXPRESSION ANALYSIS AND THEN
IT'S ALSO POSSIBLE TO SAMPLE THE
MEDIA FROM THOSE RESERVOIR WELLS
AND TO EVALUATE CYTOKINES THAT
MAY HAVE BEEN RELEASED AND
PRODUCED BY THE CULTURES.
AS A RESULT OF A DISEASE OR
TREATMENT.
AND SO OUR LUNG ON A CHIP MODEL
CAN BE USED ACROSS THE SPECTRUM
I THINK ACROSS FROM DISCOVERY
AND DEVELOPMENT FROM VERY EARLY
ON IN DISCOVERY DECIPHERING THE
DISEASE BIOLOGY THROUGH
DERISKING AND ACCELERATING YOUR
DRUG TO THE CLINIC.
I'M NOT GOING TO GO INTO A LOT
OF DETAIL AND NOTICED IN OUR
FIRST PRESENTATION BY ALFRED HE
USED THE SIMILAR PICTOFWRGRAPHI
WHICH IS GREAT TO SHOW YOU THE
DIFFERENT AREAS AND PARTS OF THE
LUNG IF YOU'RE INTERESTED IN
MODELLING ONE AREA YOU MAY WANT
TO INCLUDE SPECIFIC CELL TYPES.
FOR EXAMPLE, AT MIMETAS WE'RE
LOOK AT THE BRONCHULAR
EPITHELIUM AND THE PRIMARY
FUNCTION OF THE LUNG IS GAS
EXCHANGE AND INVOLVED IN THE
REGULATION OF BLOOD PH AND
DEFENDING AGAINST PATHOGENS.
WE CAN ALSO SEE -- WE KNOW IT'S
PARTICULARLY IMPORTANT TO BE
ABLE TO MODEL LUNG FUNCTION IN
VITRO AND LUNG DISEASES IN VITRO
BECAUSE CHRONIC RESPIRATORY
DISEASES IS A LEADING CAUSE OF
GLOBAL CANCER AND MORTALITY.
WE KNOW THERE'S AN YOU ARE FWENT
NEED TO BE ABLE ACCELERATE THE
THERAPIES AND GET THEM KNOW
PATIENTS AND PATIENTS IN NEED.
THE PRECLINICAL MODELS ARE JUST
THEY'RE NOT GOOD ENOUGH AS JEFF
INDICATED IN HIS TALK.
SO WE NEED TO KEEP IMPROVING OUR
MODELS SO THAT WE CAN GET THESE
THERAPIES TO PATIENTS AS FAST
POSSIBLE.
FIRST WE'RE GOING TO OUR LUNG ON
A CHIP MODEL WE USED
PARTICULARLY FOR AN AIR
EXPOSURE.
IMAGINE IT'S USED FOR A THERAPY
THAT MAY BE INHALED, FOR
EXAMPLE.
IN THE LEFT PANEL WE SEE WE HAVE
A PICTOGRAPH OF ONE OF OUR CHIPS
THE RED MEDIA CHANNEL IS WHERE
THERE'S MEDIA PROFUSING BACK AND
FORTH IN A BI-DIRECTIONAL
MANNER.
IN THE CENTER CHANNEL IN THE
BLUE WE HAVE AN EXTRA CELLULAR
MATRIX THAT FORM SOMEWHAT OF A
SCAFFOLD.
IN THE CENTER OF THE SCAFFOLD WE
HAVE BASICALLY NRL A HOLD TO AP
THE CELLS AND WHEN WE DO THAT
THEY ADHERE IN A 3-D STRUCTURE
TO THE EXTRA CELLULAR MATRIX
SCAFFOLD.
WHAT WE'RE LOOKING AT IN THE TOP
IMAGE 2-D, TOP DOWN.
SOMETIMES IT'S DIFFICULT TO
GRASP WHAT'S GOING ON IN A 3-D
CULTURE.
WE ALSO TRY TO PROVIDE THE
CROSS-SECTIONAL VIEWS.
THAT'S WHAT WE SEE IN THE BOTTOM
PANELS.
THERE'S TWO CROSS-SECTIONAL
VIEWS.
THE ONE ON TOP IS WHAT THE
CULTURE AFTER WE APPLIED THE
CELLS TO THE EXTRA CELLULAR
MATRIX SCAFFOLD AND THE WHITE
CELLS ADHERE TO THE BLUE AND WE
HAVE A MEDIA THAT WE FIRST USED
WHEN APPLYING THEM TO THE
CULTURE.
ONCE THE CELLS HAVE ADHERED AND
PROLIFERATED TOE ENCOMPASS THE
ENTIRE 3-D TUBULE STRUCTURE WE
CAN REMOVE THE MEDIA AND DO WHAT
WE CALL AIR LIFT TO HAVE THIS
AIR LIQUID INTERFACE SIMILAR TO
WHAT PRESENTERS WERE TALKING
ABOUT IN THE PREVIOUS TWO TALKS.
SO THE IDEA IS VERY SIMILAR IN
THE FACT THAT YOU HAVE AIR ON
ONE SIDE AND THEN MEDIA OR
MIMICKING THE BLOOD COMPARTMENT
ON THE OTHER SIDE.
THIS REALLY PUSHES THE CULTURES
TO DIFFERENTIATE.
HERE WE HAVE SOME AMINO
FLUORESCENT STAINING IMAGES OF
OUR ORGANO PLATE ERROR IS WHAT
WE'RE CALLING THIS.
WE CAN CULTURE THE CELLS OUT TO
AT LEAST 35 DAYS.
WHAT WE SEE ON THE LEFT-HAND
SIDE THE FIRST IMAGE IS A 2-D
IMAGE.
BEING A 3-D CULTURE IT'S
IMPORTANT TO KEEP IN MIND LIKE
THE STEROIDS PROBABLY THE CASE
IN THE PREVIOUS PRESENTATION IN
ORDER TO CAPTURE THE 3-D
INFORMATION YOU'RE USING A
CONFOCAL MICROSCOPE TO Z STACK
THROUGH THE HEIGHT OF THE
CHANNEL AND MAKE SURE YOU'RE
CAPTURING ALL INFORMATION ABOUT
THE 3-D OF THE CULTURE.
AND WHAT YOU CAN DO WITH ALL
THOSE IMAGES IS COMPRESS THEM
INTO A MAXIMUM INTENSITY
PROJECTION AND MAKE IT A 2-D
IMAGE.
THAT'S WHAT WE'RE LOOKING AT ON
THE BOTTOM THE INTENSITY OF THE
3-D STRUCTURE AND SEE EXPRESSION
FOR THE TUBULIN AND IF YOU
ADVANCE ONE MORE TIME WE SEE THE
NEXT IMAGE ROTATING BITS.
WHAT YOU CAN DO WHEN YOU TAKE
THE Z STACKS IS MAKE A 3-D
RECONSTRUCTION AND THAT'S WHAT
WE'RE SEEING HERE.
A ROTATING 3-D RECONSTRUCTION OF
THAT BRONCULAR TUBULE.
WE CAN ALSO SEE THE FUNCTIONING
OF THE CILIATED CELLS.
IN OUR FAITH CONTRAST IMAGE WE
CAN POTENTIALLY SEE BEATING AND
MOVING OF THE CILIATED CELLS AND
ABLE TO QUANTIFY THIS AND SEE
ANN INCREASE IN THE NUMBER OF
CILIATED CELLS OVER TIME.
WE'RE ABLE TO QUANTIFY HYPER
PLAY SHA OF THE CELLS AND --
HYPERPLASIA OF THE CELLS AND
KNOWN IN INFLAMMATION AND TISSUE
REGENERATION AND CAN SEE THERE'S
AN INCREASE IN THE COMPRESSION
OF MUC BY C AND DECREASED IN THE
EXPRESSION OF CYTOKERATIN 5 AND
HAVE UP REGULATION IN THE
GOBLET CELLS IN THE POPULATION.
I'LL MOVE TO OUR ORGAN ON A
ORGAN ON A CHIP MODEL AND THIS
IS SLIGHTLY DIFFERENT IN THE IN
THE NEXT SLIDE I GO INTO A BIT
MORE DETAIL SO WE'RE IN A
SIMILAR CHIP LIKE STRUCTURE ON
THE RIGHT AND LEFT SIDE.
IN PINK WE HAVE THE MEDIA
CHANNELS WHERE IN THIS CASE WE
HAVE ENDOTHELIAL CELL TUBULE
GROWING ON BOTH SIDES.
WHAT'S DIFFERENT HERE IS WE
DON'T HAVE AN OPEN CHANNEL.
INSTEAD WHAT WE HAVE IN THE
MIDDLE IS A VASCULAR BED
EMBEDDED WITHIN AN EXTRA
CELLULAR MATRIX CELLS.
HERE THE CELLS ARE MIXED
TOGETHER WITH FIBROBLASTS AND
SPONTANEOUSLY FORM A VASCULAR
BED AND FORM A MONOLAYER
DIRECTLY ON TOP OF THE VASCULAR
BED THOSE LUNG EPITHELIAL CELLS.
WE KNOW THE CELLS ARE
UNDIFFERENTIATED AND ONCE
THEY'VE SUSTAINED THEMSELVES, IF
YOU CLICK ONE MORE TIME WE DO AN
AIR LIFT AND ACTING AS THE BASO
COMPARTMENT AND WHERE WE ADDED
THE LUNG EPITHELIAL CELLS IS
WHERE THE AIR EXPOSURE IS
OCCURRING.
THAT'S WHERE WE SEE THE
DIFFERENTIATION.
HERE WE HAVE THE IMAGES OF THE
TIME AND I CAN TELL YOU IT'S
INCREASED DIFFERENTIATION IS
DIFFICULT TO TELL BUT BY PHASED
CONTRAST AND THE WAY WE KNOW
THIS IS DEVELOPING WELL IS
SEEING THE DARKENING OF
CULTURING OVER TIME AND THE
TUBULES IN THE ADJACENT CHANNELS
ARE REMAINING INTACT AND HOW
THANK YOU KNOW THE CULTURE IS
PROGRESSING WELL.
ANOTHER WAY TO EVALUATE THIS IS
BY TRANS EPITHELIAL ELECTRICAL
RESISTANCE AND DIP IN THE MEDIA
WELLS AND CAN MEASURE THE TIER
OVER TIME.
ACROSS MULTIPLE ITERATIONS WITH
HE SEE ROBUSTLY OVER TIME THE
TIERED VALUES CAN DECREASE WHICH
IS WHAT'S CONSISTENT WITH THE
LITERATURE AND TO DO WITH THE
DIFFERENTIATION PROCESS
OCCURRING WITHIN THE CULTURES.
I HAVE A FEW IMMUNOSTAINING
IMAGES AND PROJECTIONS AND 3-D
RECONSTRUCTION.
SO WHAT WE SHOW HERE IS JUST
SOME NICE BRONCHIAL EPITHELIAL
ORGANIZATION AND DIFFERENT
DIFFERENTITION --
DIFFERENTIATION AND THE TUBULIN
DEMONSTRATING THE CILIATED
CELLS.
THAT'S THE LONG ORTHOGONAL VIEW.
I WANTED TO POINT OUT THE CY
CYTOKERATIN 5.
WE HAVE THE EXPRESSION OF THE
5AC.
HERE WE ALSO EXPECT THAT WOULD
BE KIND OF EXPRESSED MORE
TOWARDS THE ATYPICAL SIDE AS
WELL AND WHERE WE SEE SOME OF
THE RED STAINING.
IF YOU CLICK ONE TIME WE HAVE A
VIDEO MOVING THROUGH THE
STAINING AND THROUGH THE DISEASE
STACKS.
THE FIRST IMAGE YOU SEE IS THE
BOTTOM OF THE CULTURE.
WHAT'S IMPORTANT TO POINT OUT
ABOUT THIS MODEL IS IT'S MORE
COMPLEX AND HAS NOT ONLY THE
EPITHELIUM AND ALSO PRESENT IS
THE VASCULAR BED INDIRECT
CONTACT WITH THE EPITHELIUM.
AND SO ON THE LEFT-HAND SIDE YOU
CAN SEE THOSE MORE ZOOMED OUT
2-D IMAGES OF CD 31
DEMONSTRATING THE VASCULATURE
AND PRESENCE OF A ROBUST
VASCULATURE BED AND IN THE
CENTER CHANNEL WHERE THE
EPITHELIUM ARE PRESENT AND THEN
IF YOU MOVE TO THE CENTER IMAGES
WE CAN ACTUALLY SEE THAT 3-D
RECONSTRUCTION AND VERY CLOSE
ASSOCIATION OF THE EPITHELIUM
WITH THE CD 31 VASCULAR BED.
YOU MAY BE WONDERING IS THE
VASCULAR BED FUNCTIONAL?
AND IT ACTUALLY IS.
WE CAN EVALUATE THE
PROFUSABILITY OF THE VASCULAR
BED AND FLOW DYE AND EVALUATE
THIS BY ADDING THE DYE TO THE
MEDIA CHANNEL AND IF IT'S
PROFUSABLE YOU'LL SEE WHAT YOU
SEE HERE WHICH IS THE VASCULAR
BED LIGHTING UP.
IT'S FUNCTIONAL IN BOTH CASES.
YOU CAN REPEAT IT OVER TIME.
MAYBE YOU WANT IT FLOW SOMETHING
THROUGH LIKE IMMUNE CELLS AND
BEFORE YOU FLOW THROUGH SOME
VERY APPRECIATION IMMUNE CELLS
YOU HAVE PERHAPS YOU WANT TO
UNDERSTAND IS THE VASCULAR BED
PROFUSABLE AND CAN PERFORM THE
ASSAY AND ONCE YOU'RE CONFIDENT
YOU HAVE A PROFUSABLE BED YOU
CAN START ADDING YOUR MORE
APPRECIATION MATERIAL.
WE CAN UNDERSTAND THINGS LIKE
VESSEL AREA AND TOTAL NUMBER OF
JUNCTIONS.
IF YOU'RE INTERESTED IN
UNDERSTANDING HOW COMPOUND WERE
POTENTIALLY INFLUENCING THAT
VASCULAR BED.
WE FLOWED THE DYE THROUGH BUT
WERE ABLE TO FLOW THROUGH IMMUNE
CELLS WE USED AND LABELLED WITH
CELL TRACKER.
IF YOU CLICK ONE TIME YOU'LL SEE
A VIDEO ON THE LEFT-HAND SIDE.
THE IMMUNE CELLS FLOW ACROSS THE
STOP.
-- TOP.
YOU SEE THE IMMUNE CELLS IN ONE
DIRECTION ON THE TOP AND FLOWING
THROUGH THE VASCULAR BED AND ON
THE RIGHT SIDE IS THE TIME LAPSE
IMAGING COMPLIED TOGETHER IN A
SINGLE IMAGE.
EACH COLOR REPRESENTING A
SPECIFIC TIME WHAT PATH THE
IMMUNE CELL WAS TAKING.
FOR EXAMPLE, EARLY ON THOSE ARE
MORE THE PURPLE BLUE.
YOU CAN SEE ESPECIALLY ON THE
LEFT-HAND SIDE OF THE VASCULAR
BED THERE WERE CELLS THAT TOOK
THAT PATH AND LATER ON YOUR
ACTUALLY MORE IN THE YELLOW
WHITE AND SEE WHERE THE IMMUNE
CELLS WERE LATER IN THE
PROFUSION ASSAY.
I WANT TO DEMONSTRATE THE
FEASIBILITY OF MODELLING
PULMONARY DISEASE.
WE MODELLED PULMONARY FIBROSIS
AND APPLIED A FIBROTIC COCKTAIL
TO THE CULTURES AND EVALUATED
THEIR BED ON THE VASCULAR BED
PROFUSABILITY AND DOES A COUPLE
TYPES OF EXPOSURE.
ON THE LEFT SIDE WE DIDN'T HAVE
ANYTHING IN THE CULTURES.
AND ADDED DIRECT "ON TOP OF THE
EPITHELIUM TO SEE WHAT THE
DIFFERENCE IS BETWEEN THE TWO
EXPOSURES ROOTS AND ON THE RIGHT
SIDE ADDED A FIBROSIS INHIBITOR
TO SEE IF WE COULD PREVENT THE
FIBROTIC EFFECT.
WHAT WE OBSERVED IN BOTH CASES
IN THE EXPOSURE CONDITIONS WE
SEE A LOSS OF VASCULAR BED
PROFUSABILITY THAT WAS PREVENTED
BY THE PERFUSION OF THE
INHIBITOR.
EYE AND THERE'S A TRANSITION
OCCURRING WHICH IS COMMON IN
FIBROSIS.
I THINK IT WRAPS IT UP FOR MY
UPDATE ON THE MIMETAS CHIP
MODELS.
I WANTED TO EMPHASIZE AND LET
YOU KNOW THAT AT MIMETAS WE HAVE
LOTS OF DIFFERENT SOLUTIONS FOR
YOUR RESEARCH FROM DISCOVERY,
LEED OPTIMIZATION AND SUPPORT.
WE OFFER THE PLATES AND FOLKS
CAN BUY THEM THEMSELVES AND
BRING THEM IN YOUR LABORATORY
AND FAIRLY STRAIGHTFORWARD AND
WE CAN WORK WITH YOU AND DO MORE
WORK ON OUR SIDE AND IF YOU
PREFER NOT TO BRING IT IN HOUSE
TO TO THAT.
I WANT TO THANK OUR COLLEAGUES
AND THE WORK FUNDED BY THE EU
GRANT AND THANK YOU FOR YOUR
ATTENTION AND LOOK FORWARD TO
THE PANEL DISCUSSION.
THANK YOU.
>> THANK YOU, KRISTIN.
GREAT TALK.
THE FINAL PRESENTATION WILL BE
GIVEN BY JOHN ENGLEHARDT FROM
THE UNIVERSITY OF IOWA.
JOHN, TAKE IT AWAY.
>> THANKS, JOHN.
I'M JOHN ENGLEHARDT CURRENTLY AT
THE UNIVERSITY OF IOWA.
WE'LL BE TRANSITIONING THIS
SUMMER TO THE UNIVERSITY OF
ALABAMA BIRMINGHAM.
THESE ARE MY DISCLOSURES.
ONE RELEVANT TO WHAT IS RELEVANT
TODAY.
I'LL TALK ABOUT THE UTILITY OF
FERRETS TO MODEL LUNG DISEASE.
AND THE BIOLOGICAL BASE OF THAT
CELL BIOLOGY IN THE LUNG AND HOW
THAT IMPACTS THE PROGRESSION OF
CERTAIN DISEASES AND
APPLICATIONS TO TEST THERAPIES.
WHAT YOU'VE WRITTEN HERE ARE
DISEASE MODELS IN FERRET SOME
CONSTRUCTED WITH THE NATIONAL
RESOURCE I DIRECT AND SOME ARE
ENVIRONMENTAL STIMULUS INJURY
INCLUDING CYSTIC FIBROSIS,
ASTHMA AND SMOKING MODELS HAVE
BEEN VERY SUCCESSFUL AT THE
UNIVERSITY OF ALABAMA.
BRONCHITIS AND EMPHA SEE 345
RARCHBD I'LL DISCUSS THE BIOLOGY
BETWEEN IPF OR GLIAL MODELS IN
THE FERRET AND THERAPIES IN THE
LATTER.
IT'S IMPORTANT WHEN COMPARING
DIFFERENCES IN THE TYPES OF CELL
TYPES THAT SPAN THE AIRWAY,
THEIR DISTRIBUTION AS WELL AS
ANATOMICAL SITES.
MUCOSA GLANDS AND THE IONOCYTES
THAT ARE ASSOCIATED WITH GLANDS
EXPAND AND DELAYS NO CARTILAGE
WIN THE INTERLOPIN AIRWAYS AND
THE IONOCYTES ARE LOCATED ATHET
PROXIMAL END TO THE TRACHEA AND
RELEVANT TO DISEASES LIKE IPF
AND DISTRIBUTION OF BASAL CELLS
EXTEND TO THE TERMINAL
BRONCHIOLES GOING TO THE AIRWAYS
IN RODENTS.
AND RODENTS DON'T HAVE
RESPIRATORY BRONCHIOLES.
AND SO THESE DIFFERENCES IN CELL
BIOLOGY AFFECT PROGRESSION OF
CYSTIC FIBROSIS IN THE TEE
EFFECTIVE GENE IN THE FTR GENE.
THE RIGHT TWO PRANLS AND THE
MUCOSA GLAND AND THE LUMEN OF
THE AIRWAY AND THE MICE DON'T
GET LUNG DISEASE.
THERE'S DIFFERENCES IN THE
DISTAL CONDUCTING AIRWAYS AND
RESPIRATORY BRONCHIOLES BETWEEN
RODENTS AND HUMANS AND FERRETS
AS WELL AS PIGS.
THE AREAS CONTAIN BASAL CELLS AS
WELL AS A CLUB SECRETSECRETATORS
AND SHOWN TO BE DIFFERENT
BETWEEN RODENTS AND HUMANS
INCLUDING AND THE CELL TYPES
HAVE BEEN SHOWN TO HAVE
SPECIALIZED PROGENITOR CAPACITY.
YOU SEE DOUBLE TRANSGENIC MICE
ON THE LEFT AND THIS CAN BE
STIMULATED WITH TAMOXIFEN TO
INDUCE A RECORDER SWITCH
SWITCHING TO GFP.
THIS IS THE ALPHA SMA GENE FATE
MAPPING BLOOD VESSELS, VASCULAR
SMOOTH MUSCLE AND SMOOTH MUSCLE
IN THE DISTAL AIRWAY AT THE
BRONCHIOLE ALVEOLAR JUNCTION AND
WHERE IN MICE A STEM CELL EXISTS
THAT REPAIRS THE DISTAL AIRWAY
FOLLOWING INJURY.
THE SAME MODEL GENERATED WITHIN
PER ITS AND THE DISTAL AIRWAY IS
WHERE THE TERMINAL BRONCHIOLE
CELL EXISTS AND ONE THE DRIVER
THE SMOOTH MUSCLE BELOW THE CLUB
CELLS VERY DIFFERENT PICTURE
ANATOMICALLY AND THIS IMPACTS
THE PROGRESSION OF PULMONARY
FIBROSIS FOLLOWING MICE IN
INJURY.
AND LOOKING AT THE RISK IN
PULMONARY CARTILAGE AND ONE SEES
THE THREE LARGEST SPECIES,
FERRET, AND PIG ARE CLOSE TO
HUMAN LUNG.
I'LL TALK BRIEFLY ABOUT THE
INJURY MODEL IN THE FERRET IN
WHICH WHAT WE'RE LOOKING AT HERE
IS SINGLE NUC SEQ OF EPITHELIAL
CELLS AND SHOWING THE CELL TYPES
ONE CAN SEE FOLLOWING GLIOMYCIN
INJURY AND THE CHANGES THAT
OCCUR.
YOU CAN SEE TWO CELL TYPE AND
BASALOID LIKE CELL POORLY MODELS
IN MICE COMPARED TO IPF IN
HUMAN.
AND THERE'S A REPAIR IN THE
DISTAL AIR SPACES.
THIS PHENOTYPE OF TP63 CARE 7
POSITIVE MARK BY THE ARROWS DOES
NOT EXIST IN MOUSE LUNG AND IT'S
THOUGHT THIS MIGHT CONTRIBUTE TO
DIFFERENCES IN THE PERSISTENCE
OF INJURY.
THIS IS THE RESULT OF FIBROSIS
AND THE ALVEOLI AND THE PROXIMAL
AIRWAY WITH THE NOTCH SIGNALLING
AND HIGHLIGHTING THE BASALOID
CELLS WITH THE YELLOW ARROWS AND
SHOWN WHAT THE NORMAL AIRWAY
LOOKS LIKE ON THE PANEL A.
THAT'S A PORTION OF THE LUNG
SECTION AND THE MORE DYSPLASTIC
PROXIMALIZATION WHERE THE
AIRWAYS INVADE THE AIR SPACES
AND EVENTUALLY LEAD TO
IRREVERSIBLE DAMAGE AND DEATH.
AND THE BRONCHIAL SMOOTH MUSCLE
WE BELIEVE CONTRIBUTE TO
MYOFIBROBLASTS AND THIS IS SHOWN
IN THE FERRET PRIOR TO BLEOMYCIN
INJURY AND SEE THE ASMA AND THE
NEXT AIR I WANT TO TALK ABOUT
HAS TO TO WITH UTILIZING THE
FERRET MODEL FOR TESTING GENE
THERAPIES OR RNA THERAPIES FOR
CYSTIC FIBROSIS.
WE HEARD ABOUT THE CFTR CHANNEL
WHICH TRANSPORTS BY CARBONATE
AND CHLORIDE IN THE ABSENCE OF
THE FUNCTION.
AND THE AIRWAY SURFACE FLUID
BECOMES DEHIYDRDEHYDRATED THE P
LOWER AND VISCOSITY IS CLEARED
AND LEADS TO INFECTION.
THE CELL TYPES MARK IN THE BOX
HERE HIGHLIGHT DIVERGENT LEVELS
OF MRNA EXPRESSION AND PROTEIN
EXPRESSION WITHIN THE CELLS FROM
GREATER 15% TO 90% EXPRESS CTFR.
IT'S UNCLEAR WHETHER OR NOT THE
CFTR EXPRESSION FROM A GENE
THERAPY STANDPOINT HAS TO
RECAPITULATE THE ENDOGENOUS
EXPRESSION PATTERN TO REVERSE
DISEASE.
THAT'S ONE THING I'LL TOUCH ON
HERE.
AND WE LOOKED AT THE KNOCKOUT
511D IN THE ABSENCE OF THE FCFR
MODULATOR THAT CAN CORRECTLY
RESTORE GAITING OF THE MUTANT
CHANNEL -- GATING OF THE MUTANT
CHANNEL IS MORE USEFUL BECAUSE
WE CAN TURN IT ON AND OFF AND
HAVE IT RELEVANT TO GENE THERAPY
INCLUDING CAN IT REVERSE DISEASE
OR PROGRESS THE ONSET OF
DISEASE.
NOW, THIS IS THE TYPICAL WORK
FLOW WHEN MY GROUP INTERACTS
WITH OTHERS FROM THE OTHER SIDE
TO EVALUATE FERRETS.
SOME OF THE FIRST MOST IMPORTANT
QUESTIONS AND IF ONE'S
CONSIDERING A VIRUS WHETHER OR
NOT THEIR TROPISM DIFFERENCES
BETWEEN HUMAN AND FERRET AND
LESS CONCERN FOR LNPs.
WE THEN TYPICALLY MOVE TO
REPORTER AND INTERFACE AND
CULTURES THAT -- WHERE YOU CAN
EXPRESS CREE AND DRIVE THE
REPORTER EXPRESSION LIKE I
SHOWED IN VIVO TO GFP AS A
SENSOR.
AND THE NEXT LEVEL WOULD BE
FUNCTIONAL CORRECTION USING A
CFTR WITHIN THE VIRAL VECTOR OR
MRNA AND LOOK FOR
ELECTROPHYSIOLOGIC COLLECTION IN
AIR INTERFACE CULTURES.
THEN MOVING IN VIVO, I PREFER TO
USE THE UNEQUIVOCAL DETECTION
USING THE CREE REPORTER AND ASK
QUESTIONS WHAT CELL TYPES ARE
TARGETED.
WHAT CELL TYPES USING PHENOTYPIC
MARKERS.
AND THEN THE MORE DIFFICULT
QUESTION THEN MOVE IN VIVO INTO
THE DISEASE CYSTIC FIBROSIS
USING HUMAN CFTR AND THERE'S
SHORTER TERM AND ASK FOR DISEASE
REVERSAL AND A CF FERRET WITH
ROSEA TG WITH CREE ASKING THE
VIRAL VECTOR OR mRNA CAN
PENETRATE THE MUE CAS BARRIER.
I'LL DISCUSS TESTS WITH THE
LIPID NANO PARTICLE.
SOME OF THE FIRST STUDIES WE DID
WERE IN AIR INTERFACE CULTURES
AND SEE IN THE UPPER RIGHT HAND
CHANNEL THE SWITCH OF CELLS TO
CFTR POSITIVE AND THE ONES
TARGETED IN THE BOTTOM PANEL.
YOU CAN SEE THIS IS MEASUREMENTS
WHERE THE BLUE WERE LOOKING AT A
COMPARISON BETWEEN A RELEVANT
RNA AND COMPARED TO WILD TYPE
UNTRANSFECTED.
YOU CAN SEE WITH THE HUMAN CFTR
WHAT LOOKS AT THE BLUE ARROWS
THE ACTIVATION OF CFTR IS ABOUT
50% AND INHIBITION WITH THE CFTR
INHIBITOR THAT ACTS ON FERRET
AND YOU CAN SEE THE LIPID NANO
PARTICLE CORRECTS SHORT CIRCUIT
CURRENT FROM 50% TO 75%
APPROXIMATELY.
NEXT WE MOVED IN VIVO WITHIN
FERRET, TRANSGENIC FERRET AND
DEMONSTRATED THE TRANSFECTING
CREE.
WE SEE THE HIGH LEVEL
TRANSFECTION OF THE TRACHEA
CONVERSION TO EGFP AND THE
INTERLOPER AIRWAYS ON THE RIGHT.
AND -- INTERACHAL AIRWAYS AND
SEE THE INTRALOBAR AIRWAY.
AND CAN TEST FOR TRANSFECTION OF
CELLS AND GUIDE THE PHENOTYPING.
WE'RE LOOKING AT A FERRET AND
THE AIRWAY IN THE TRACHEA ON THE
TOP.
AND LOCALIZATION OF CFTC.
AND LOCALIZATION OF CFTR IS
SHOWN ON THE RIGHT WITH A LUNAR
VEHICLE.
THE YELLOW AIRS HAVE HIGH
TRANSFECTION AND SEE THE
POTENTIAL SECRETORY CELL IN THE
CENTER AND ONCE THE INCREASED
ABUNDANCE OF CFTC AT THE
MEMBRANE AS CO-LOCALIZED WITH
THE CELLS.
SO, WHAT CELL TYPES ARE
TRANSFECTED?
SO IN THESE PANELS WE'RE SHOWING
TRANSFECTION WITH TOMATO MRNA
AND LOCALIZATION WITH THE TOP
PANELS.
ONE CAN SEE AND FOX J1 WHICH
LABELS THE NUCLEUS OF CILIATED
CELLS ARE HIGH TRANSFECTED.
ON THE BOTTOM PANEL YOU CAN SEE
WITH THE YELLOW TWO ARROWS
EXPRESSION OF TOMATO WITHIN
SECRETORY CELLS EXPRESSING THE
TOMATO AND MODIFIED AC.
THESE ARE OTHER EXAMPLES.
BASAL CELLS IN VIVO VERY FEW
BASAL CELLS WERE TRANS VECTED
MARK BY P63 ON THE LEFT.
ON THE RIGHT ARE THESE PULL MON
IONOCYTES.
AND IF ONE HONES ON SECRETORY
CELL MARK BY THE RED AND YELLOW
MARK IN A TRANSFECTED SECRETORY
CELL.
AND THIS IS CELL TYPE
SPECIFICITY.
CAN THE mRNA CLEAR THE DEFECT?
THE FIRST THING WE NEEDED TO DO
WAS TO DEVELOP AN ASSAY THAT WE
FELT WAS ROBUST AND CAPABLE OF
DETECTING CFTR IMPACT ON
CLEARANCE.
WE USED PET CT AND AND WE SEE A
DEPOSITION MOVING UP THE TRACHEA
AND ONE UP AND OFF AND ONE CAN
QUANTIFY THIS USING THE RAMENT
OF PERCENT THAT'S CHEERED AND
WHAT ONE SEES ON THE BLUE LINE
ARE BASELINE STUDY AND THEN
PROGRESSIVELY WITH TIME OFF THE
AIR 770 THE DE DECLINE WITHIN
THE MUCOUS CLEARANCE AND THE
GREEN LINE BOUNCES BACK UP TO
WHAT IT WAS.
WE FELT CONFIDENT THAT THIS WAS
INDEXING CFTR ACTIVITY AND THIS
IS QUANTIFIED AS THE CLEARANCE
RATE WITHIN THE FIRST SIX
MINUTES.
THE QUESTION WAS DOES THE LIEU
FLOOR CFTR CORRECT THE MCC
DEFECT SO THE STUDY WAS TO FIRST
SCAN BASELINE MCC WITH CF
FERRETS OFF THE MODULATOR AND
THEN WHEN THEY REACHED A
BASELINE OF 20 TO 40 TO TREAT
WITH THE HUMAN CFTC.
AND CLEARANCE AFTER THAT.
WHAT WE'RE LOOKING AT THE HERE
ARE BASELINE SCANS IN EIGHT
ANIMALS FOLLOWED BY THE HUMAN
LMP DELIVERY.
SEE SIGNIFICANT IMPROVEMENT AND
CLEARANCE BOTH ON THE QUANTIFIED
ON THE LEFT.
AND ONE COMPARES THAT TO THE
LUNAR TOMATO mRmRNA THERE WAS N
SIGNIFICANT DELTA AND
QUANTITIFQUANTI
QUANTITIFYING -- QUANTIFYING
THE DIFFERENCE IN TOMATO AND
HERE EVALUATED BY NOVA AND HERE
THE PAIRED ANALYSIS FOR THE TWO
GROUPS.
SO THE LAST QUESTION BEFORE I
SUM UP IS CAN THE LNP PENETRATE
THE MUCOUS BARRIER.
THIS IS AN EXAMPLE OF A CF
FERRET TAKEN OFF THE MODULATOR
FOR FIVE MONTHS.
YOU CAN SEE ON THE RIGHT THIS
MUCOUS BEARING DOWN ON THE
SURFACE OF THE INTERLOPER
CONDUCTING AIRWAY AND THIS IS
FOLLOWING LUNAR CREE DELIVERY
SWITCHING ON THE CFG REPORTER.
AND YOU CAN SEE AT LEAST IN THIS
EXAMPLE RIGHT HERE THERE'S
PENETRATION TO THE LIPID TO
TRANSFECT THE SURFACE AIRWAY
EPITHELIUM.
TO SUMMARIZE, CF FERRETS AND
OTHER FERRET MODELS CAN AID IN
THE EVALUATION OF LUNG DISEASE
PATHOPHYSIOLOGY AND THERAPIES.
THERE'S SPECIFIC ASPECTS OF THE
FERRET LUNG AND CELL BIOLOGY AND
ANATOMY THAT MAKE IT A GOOD
MODEL FOR LUNG DISEASES AND IT
DELIVERS mRNA AND EFFECTIVE
CLEARANCE DEFECT WITHIN CF
FERRETS AND THE IMPROVED MCC
WITH THE HIGHEST TRANSFECTION OF
CILIATED CELLS LOWERS IONOCYTES
AND IT'S IMPORTANT BECAUSE THE
PATTERN OF TRANSFECTION IS NOT
IDENTICAL TO THE ENDOGENOUS
EXPRESSION AND INDICATES OTHER
CELL TYPES MAY BE ABLE TO PICK
UP THE SLACK AND RECONSTITUTE
AIRWAY CLEARANCE.
AND THEN I'LL SAY LASTLY THE
STUDIES HELPED TO MOVE LUNAR
THROUGH CLINICAL TRIALS AND
WE'RE CURRENTLY UNDERGOING
TRIALS ONE THE LNP.
I'D LIKE TO THANK THOSE IN MY
LABORATORY AND THE TREMENDOUS
NUMBER OF COLLABORATORS WORKING
WITH THE LARGER ANIMAL MODEL IS
DEFINITELY A TEAM SCIENCE.
SO THANK YOU.
>> THANK YOU.
I ALSO WANT TO TAKE THE
OPPORTUNITY TO THANK OUR
SPEAKERS FROM SESSION 1 SHOWING
THE FOREGROUND FROM MODEL AND
TOOL DEVELOPMENT.
AS PART OF OUR TRANSITION TO
PANEL DISCUSSION HERE I WANT SO
SHOW OUR EXPERIENCE IN THE SPACE
AND WHICH I THINK WE'LL FIND
SYNERGIES WITH THE PRESENTATION
WE HEARD IN SESSION 1.
WE'VE ENGINEERED LUNG TISSUE
MODELS FOR TESTING.
A TOPIC WE'VE INVESTIGATED IS IN
THE INTERACTION.
THE LUNG IS ONE OF THE LARGEST
INTERFACE BETWEEN TOUR BODY AND
THE OUTSIDE ENVIRONMENT.
SO WE HAVE POLLUTANTS AND VIRUS
AND IT'S BECOMING A ROBUST FOR
STUDYING DISEASE MECHANISM AND
FOR TESTING THERAPEUTICS.
HOWEVER, AND THERE'S BEEN ONE
MAJOR LIMITATION IS MOST MODEL
HAVE ETHICAL INCONFIRMATION AND
WE PUT STEM CELLS INTO A SETTING
A
AND THEY'LL CAUSE A SURFACE WITH
CILIA CLEARANCE TO HAPPEN IN
CLOSE INTERFACE WHICH BECOMES
DIFFICULT TO ACCESS WHEN IT
COMES TO INTRODUCING THE
ENVIRONMENTAL THREATS LIKE
POLLUTION OR VIRUS OR BACTERIA.
IN THE PAST FEW YEARS US AND
OTHER GROUPS HAVE BEEN COMING UP
WITH STRATEGY TO REDUCE THE
POLARITY AND MOST USE A STRATEGY
DRAWING SUPPORT FROM THE CULTURE
AT THE BEGINNING OR END OF THE
DIFFERENTIATION WHICH SERVES AS
AN EFFECTIVE STRATEGY TO REVERSE
POLARITY AND SIMILAR TO WHAT WE
SEE IN THE NATIVE LUNG.
AND THE SURFACE I COAT WITH
CILIA AND PADDLING IN A
SYNCHRONIZED MATTER CAN BRAVE
THE MOTILITY OF WHAT WE ENGINEER
AND WE CAN TRACK THE MOTILITY OF
THE ORGANOID AND CORRELATE THIS
WITH CILIA MOTILITY AND GET
CELLS FROM HEALTHY OR PCD CELLS
AND CAN SERVE AS A SCREENING
PLATFORM.
WE'RE MAKING MODELS MORE AUTO
MATED AND YOU HAVE THIS ORGANOID
AND DRAW THE SPIRAL ON THE
SURFACE UNTIL I BUMPS INTO A
WALL OR ORGANOID AND DEVELOPED A
SWARM ANALYSIS LIKE WATCHING A
GROUP OF INSECTS MOVING AROUND
AND NOW WATCH ORGANOID MOVING
AROUND POWERED BY CILIA AND TELL
THE DIFFERENCE BETWEEN THEY WILL
THE INDIVIDUAL VERSUS THE
ORGANOID BEING TRIGGERED WITH
AIR POLLUTION.
HE WE CAN COME UP WITH ASSAYS
AND ALTER THE PIPELINE COMBINED
WITH AUTO MATED IMAGING AND WE
HAVE FUNCTION WITH WHOLE TISSUE
THROUGHPUT.
FOR THE ORGANOIDS TO SPIN AND
ROTATE IT HAS TO WORK IN A
COORDINATING MANNER AND HAVE
POLARITY WHICH ALLOWS US TO
INTRODUCE POLLUTANT BACTERIA
VIRUS FOR THERAPEUTICS WE INTEND
TO DELIVER INTO THE AIR SPACE.
WE HAVE TO BEAR IN MIND IT'S
STILL RECAPITULATING WHAT IT
LOOKS LIKE AND LOOK AT THE
POLARITY.
WE SHOULD CONSIDER INTRODUCING
THE BASAL STROMAL ENVIRONMENT
AND THE MEMBRANE BETWEEN
EPITHELIAL AND STROMAL CELLS.
THIS IS ECHOING THE PLATFORM WE
THINK IT'S ESSENTIAL TO
RECAPITULATE THE GEOMETRY OF THE
LUNG TISSUE AND IT'S CONSTANTLY
BRANCHING TUBULES LEADING TO
GENERATIONAL BRANCHES.
PUTTING MORE INSIGHT INTO HOW
THE PATHOLOGY SPECIFY AROUND
DIFFERENT PARTS OF THE
RESPIRATORY TRACT.
WITH THIS IN MIND AND WHERE WE
PUT STEM CELLS INSTEAD OF THE
INDIVIDUAL CELLS AND RATHER
EMBED THEM IN THE HYDROGEL IN A
SPATIALLY CONSTRAINED MANNER.
WE CAN EXTRUDE THE CELL INTO
ALIGN AND OVER TIME THE CELL CAN
SENSE THE PRESENCE OF
SURROUNDING CELLS AND FORM THE
TUBULE.
IF YOU MAKE THIS FROM AIRWAY
STEM CELLS WE CAN GET ROBUST
CLEARANCE WITH TYPICAL CELLS YOU
WOULD FIND IN THE AIRWAY.
AND WE CAN APPLY SIMILAR
STRATEGIES AROUND USE THE CELL
LINE WHICH YOU CAN SEE AND AGAIN
OVER ABOUT A MONTH OF CULTURE WE
CAN GENERATE FROM THE TUBULE OF
THE TYPE 2 CELLS WITH THE
INTERCONNECTED LUMEN.
OF CURSE I WANT TO THANK ALL THE
FOLKS IN THE LAB WHO MADE THE
WORK POSSIBLE AND ALSO OUR
AMAZING COLLABORATORS AND
FUNDING AGENCIES.
WITH THAT I'D LIKE TO TRANSITION
TO OUR PANEL DISCUSSION.
WE HEARD OF DIFFERENT MODELS FOR
MIMICKING THE LUNG TISSUE IN
HEALTH AND DISEASE AND CHIP AND
ORGANOID MODELS AND THEY'VE BEEN
USED TO TACKLE DIFFERENT LUNG
DISEASES FROM CYSTIC FIBROSIS
AND LUNG DISEASE TO PULMONARY
FIBROSIS AND GENE THERAPY.
NOW I'D LIKE TO TRANSITION TOE A
PANEL DISCUSSION AND TURN TO MY
MODERATOR INTEREST SHERIDAN TO
BRING THE FIRST QUESTION TO OUR
PANEL.
WE CAN STOP SCREEN SHARING NOW.
THANK YOU.
>> THANK YOU, CHARLIE AND THANK
YOU TO ALL OF OUR SPEAKERS.
DR. MOFFITTS IS ALSO JOINING OUR
PANEL SO IF YOU HAVE ANY
QUESTIONS FOR HIM, PLEASE FEEL
FREE TO ASK THAT AS WELL.
AS A REMINDER USE THE Q&A TOOL
AT THE BOTTOM OF THE ZOOM SCREEN
TO ENTER ANY QUESTIONS YOU HAVE.
SO IN THE MEANTIME WHILE WE
AWAIT SOME QUESTIONS I WILL GO
AHEAD AND ASK THE FIRST
QUESTION.
I LIKE AT MODELS AND THERE'S
STRENGTHS AND WEAKNESSES WITH
ALL MODELS.
IT'S HARD TO RECAPITULATE
EXACTLY WHAT HAPPENS IN A NATIVE
TISSUE IN A GIVEN MODEL
ESPECIALLY NATIVE HUMAN TISSUE.
SO WONDERING IF THE PANEL COULD
COMMENT ON SOME OF THE STRENGTHS
AND WEAKNESSES OF THE MODELS
THAT YOU HAVE EXPERIENCES
WORKING WITH HOW THEY ULTIMATELY
MAY COMPLEMENT EACH OTHER.
I DON'T KNOW WHO WOULD LIKE TO
GO FIRST.
>> I'LL START OFF FIRST.
WHAT'S DIFFICULT TO MODEL IS THE
VIRAL BASED THERAPY ANYTHING CAN
HAPPEN WITH THE CO-RECEPTORS.
THE BEST WAY TO RERISK -- DERISK
THAT IS LOOK AT THE CELL TYPES
THAT ARE TRANSDUCED AND MAKE
SURE THEY'RE SIMILAR AND THE
BOCA VIRUS IS ONE THE FERRET
DOESN'T MODEL THE TROPISM.
IT'S ONE OF THE REASON WE
HAVEN'T DONE THE NCC EXPERIMENT
IN THE FERRET BECAUSE THERE'S NO
TRANSDUCTION WITH THAT VIRUS.
BUT IT'S HYDROTROPIC AND YOU
HAVE TO KNOW THE QUESTION YOU'RE
GOING TO ASK.
IF I CAN ASK ABOUT STEM CELL
BIOLOGY IN THE LUNG OF MICE AND
I'LL TWO TO THE MOUSE FIRST BUT
EVENTUALLY THE QUESTIONS FOR MY
RESEARCH TEND TO MOVE THROUGH AN
AREA THAT IS NOT ADEQUATELY
MODELLED IN MICE AND WHY WE USE
FERRETS.
>> I COMPLETELY AGREE, JOHN.
I THINK SOME OF THE REALLY
INTERESTING PARTS ABOUT THIS AND
I THINK FOLKS HAVE HEARD AROUND
DIFFERENT THERAPEUTIC APPROACHES
THAT HAVE BEEN VALIDATED IN THE
MODELS.
THOSE ARE GREAT FAST FOLLOWERS
BUT WHAT HAPPENS IF YOU'RE
LEVERAGING NEW MODALITIES?
YOU DON'T KNOW WHAT TO TRUST
YET.
THIS IS WHERE THE STRENGTHS OF
THE MULTIPLE MODELS COME INTO
PLAY BECAUSE YOU START
EVALUATING THE THERAPEUTIC
HYPOTHESIS FROM RAIN ORTHOGONAL
STANDPOINT AND IT'S ALMOST LIKE
A WEIGHT OF EVIDENCE, OKAY, THE
MODELS ARE LINING UP FOR WHAT'S
EXPECTED.
I THINK THIS IS A REASONABLE
SURROGATE FOR WHAT I'M TRYING TO
ACCOMPLISH.
THAT'S EASY IF YOU'RE FOLLOWING
DOWN A PATHWAY ALREADY
ENBLAZENED BUT YOU HAVE TO BAKE
IN SAFEGUARDS IF YOU HAVE LESS
CERTAINTY AROUND CLINICAL DOSE
PROJECTION.
YOU MAY BE FACED WITH A
SITUATION EVEN IF YOU DON'T HAVE
A SOLID IN VITRO MODEL YOU'VE
HEARD ABOUT TODAY, YOU MAY BE
FACED WITH A SITUATION WHERE YOU
HAVE TO GO LOW AND SLOW IN THE
CLINIC THAT CAN PROTRACT
CLINICAL DEVELOPMENT.
THE MORE YOU CAN LEVERAGE THE
UNIQUE TOOLS TO FIGURE THINGS
OUT THE BETTER OFF YOU'LL BE.
>> TO RESPOND TO THAT, I ALSO
WANT TO MAKE THE POINT THAT YOU
CAN LEARN A LOT FROM THE MODEL
THAT DOESN'T REPRODUCE THE HUMAN
DISEASE IF YOU ASK THE RIGHT
QUESTIONS.
THE REASON I POINTED OUT THE
AIRWAY SMOOTH MUSCLE AND HAVING
THOSE GENERATE FIBROBLASTS
DOESN'T HAPPEN IN THE MOUSE.
AND MULTIPLE PEOPLE HAVE
REPORTED THAT.
I DON'T QUITE UNDERSTAND THE
BIOLOGY AND I WANT TO BECAUSE IF
YOU UNDERSTOOD WHY GLIOMYACIN
INJURY IN A MOUSE IS MORE
REFERSABLE THAN A FERRET AND
PULMONARY FIBROSIS IN HUMAN
THERAPEUTICALLY YOU CAN
POTENTIALLY UTILIZE THAT.
>> MAYBE I CAN GIVE MY TWO CENT
ON IS THE COMPLEX IN VITRO
MODELS.
I THINK IT'S A NEW AND EXCITING
SPACE AND PEOPLE ARE OFTEN
EXCITED TO START USING THE
MODELS BUT I ALWAYS CAUTION
FOLKS AND SAY DON'T BRING THIS
TECHNOLOGY INTO YOUR LAB UNLESS
HAVE YOU A GAP.
UNLESS THERE'S A NEED.
IS THIS A NEED FOR ADDITIONAL
CELL TYPES AND IS THE TARGET IN
YOUR FIBROBLAST AND DOES IT
CROSS TALK AND DO YOU NEED MEDIA
PERFUSION THROUGH OR SIT ENOUGH
TO USE A 2-D CULTURE OR STEROID?
AND ON THE FLIP SIDE MAYBE
YOU'RE ANIMAL MODELS DON'T
EXPRESS THE TARGET AND THIS IS
OFTEN THE CASE FOR SOME OF THE
MORE NOVEL MODALITIES YOU MAY
NEED A MORE HUMAN-BASED SYSTEM
AND I THINK THAT'S WHERE I SEE
THE COMPLEX OF THE IN VITRO
MODELS AT THE FOREFRONT.
IT ALSO GOES BACK TO WHAT IS
YOUR RESEARCH QUESTION AND
THAT'S GOING TO HELP DEFINE WHAT
MODEL YOU CHOOSE.
>> WE COME FROM A TISSUE
ENGINEER PERSPECTIVE AND THEN
ONCE YOU HAVE THE MODEL IN
PLACE, WHAT QUESTION ARE YOU
GOING TO ASK USING THE MODELS
AND WITH COLLABORATORS WE
UNDERSTAND THE LUNG PATHOLOGY
AND TRY TO FIND BEST MODELS TO
ANSWER THE BEST QUESTION.
ALL RIGHT, WE'LL ENCOURAGE THE
ATTENDEES TO POSE YOUR QUESTIONS
IN THE Q&A SESSION AND LOOKS
LIKE WE HAVE A COUPLE IN THE Q&A
ALREADY.
THERE'S A QUESTION BEING ASKED
TO ONE SPECIFIC SPEAKER AND
WE'LL USUALLY ASK THE SPEAKER TO
ADDRESS THE QUESTION DIRECTLY
AND HAVE IT MORE GENERAL TO THE
PANEL.
I'LL BRING UP OUR NEXT QUESTION
IS IT IMPORTANT TO TAKE A
REDUCTIONIST APPROACH TO EARLY
DRUG DISCOVERY SUCH AS FOCUS ON
MODELS FOR HIGH THROUGHPUT
SCREENING GIVEN THE COMPLEXITY
OF THE LUNGS AND CELL TYPE OF
THE EFFECT.
>> YEAH, IT'S REALLY HELPFUL TO
DO THAT AND BREAK IT DOWN.
YOU HAVE TO THINK ABOUT THE
DISEASE YOU'RE TRYING TO TREAT
AND HOW WELL YOU CHARACTERIZE
THE BIOLOGY THAT YOU'RE TRYING
TO INTERVENE WITH THE MODALITY.
I THINK THERE'S WAYS YOU CAN
LEVERAGE A LOT OF THESE HIGHER
THROUGHPUT TECHNOLOGIES TO TRY
AND NARROW DOWN IN ON THE
INTENDED BIOLOGY AND THE
EFFICACY PROFILE AND YOU'LL BE
FLYING BLIND THOUGH THE LARGER
IN VIVO SAFETY CONSIDERATIONS
PARTICULARLY AROUND FOR SMALL
MOLECULE THAT MAY INCUR LATER ON
BUT THAT'S OKAY BECAUSE AS YOU
START TO UNDERSTAND WHAT ARE THE
PRODUCT ATTRIBUTES THAT ARE VERY
BENEFICIAL FOR EFFICACY I THINK
THAT'S HOW YOU CAN START TO
STEER IN THAT DIRECTION.
REGARDLESS OF LUNG OR SLEEP OR
ANY OTHER INDICATION IS YOUR
AREA OF INTEREST.
KRISTIN, DO YOU AGREE WITH THAT?
>> I DO.
I THINK ESPECIALLY BEING FROM
THE MORE HIGH THROUGHPUT SPACE
SO WE ARE OFFERING THESE MORE
COMPLEX MODELS IN THE HIGH
THROUGHPUT CAPACITY SO THAT
FOLKS CAN AS QUARTERLY AS
POSSIBLE GET THE COMPLEXITY BUT
THEN ALSO EARLY AND QUICKLY BE
ABLE TO KIND OF UNDERSTAND
WHETHER WE SHOULD BE PROGRESSING
THE MOLECULES THROUGH THE
PIPELINE.
>> I'LL MAKE ONE COMMENT THAT IT
DEPENDS WHAT YOUR THERAPEUTIC
IS.
OF COURSE I GRAVITATE TO THINK
ABOUT CYSTIC FIBROSIS BECAUSE IT
SPANS THE CHEMICAL SPACE AND
BIOLOGICAL TO THE mRNA AND LNP
WHICH IS STILL DIFFERENT.
I THINK SO IF YOU TALK THE SMALL
MOLECULES FOR THE SCREEN AND
SCREEN IN THYROID CELLS IN THE
ORIGINAL STUDIES THAT WERE DONE
IS FINE BECAUSE THE TARGET OF
THAT WAS THE ACTUAL GATING OF
THE CFDR CHANNEL AND THERE'S
WAYS TO EVALUATE THAT.
WHEN YOU THINK ABOUT A BIOLOGIC
AND ALL THE VARIABLES HOW YOU'LL
CORRECT AIRWAY EPITHELIUM, THEN
I GRAVITATE TO SOME AIR LIQUID
INTERFACE TYPE OF SCREEN EVEN IF
IT'S SEMI HIGH THROUGHPUT WHICH
VERTEX IS KNOWN FOR DOING.
>> GREAT, THANK YOU.
I'LL GO AHEAD AND ASK THE NEXT
QUESTION.
THIS WAS DIRECTED TO DR. MOFFITT
DIRECTLY BUT I THINK IT MAY BE
RELEVANT FOR THE OTHERS TO WEIGH
IN AS WELL IF THEY HAVE
THOUGHTS.
SO THE QUESTION WAS ASKING IF
YOU COULD COMMENT ON ANY OF THE
PROCESSES, CHALLENGES, HURDLES
IN DEVELOPING AND ADVANCING
ALLOSTERIC MODULATORS.
>> OH, THAN AN EASY ONE.
AT HIGH A LEVEL IF YOUR FOCUSSED
ON THE SAFETY YOU'LL PERCEIVE
WHETHER IT'S AN ALLOSTERIC
MODULATOR OR NOT AND TRYING TO
CHARACTERIZE THE SAFETY PROFILE
AND TARGET ORIGINS OF SAFETY AND
SAFETY MARGIN AND EFFICACIOUS
DOSE AND I THINK MORE WHERE
WE'RE COMING FROM IS MORE ON THE
EFFICACY SIDE OF THINGS.
THAT'S WHERE YOU ARE HAVING A
GOOD UNDERSTANDING OF THE
BIOLOGY AND CHARACTERIZING THE
OF THE CHANGE OF THE RECEPTOR
WHY IMPACT BINDING AND HOW IT
BEHAVES AND IN VIVO ANY SPECIES
SELECTION BECAUSE THAT'S ONE OF
THE IMPORTANT EARLY DRIVERS ONCE
YOU GET BEYOND THE IN VIVO
CHARACTERIZATION.
I'LL TURN IT TO OTHERS FOR THEIR
THOUGHTS.
>> THE BIOLOGICAL VARIABILITY AS
WITH PRO VIRUSES IS THEY ARE
BIND TO GLYCOPROTEINS IN A WAY
YOU WOULDN'T HAVE PREDICTED SO I
AGREE.
>> THANK YOU.
SO, WE'LL MOVE ON TO THE NEXT
QUESTION FROM OUR Q&A, MANY RARE
GENETIC LUNG DISEASE SUCH AS
CFTR MUTATION HAVE VARIANTS AND
WHAT ARE THE PANEL'S THOUGHTS
HOW TO PRIORITIZE THE VARIANTS?
COULD THERAPY OVERLAP BETWEEN
GENES?
>> YOU'LL GO.
A COMMENT FROM ASSIST -- A
CYSTIC FIBROSIS PATHWAY THERE'S
NONSENSE MEDIATED DECAY.
IF YOU'RE GOING TO TARGET THAT
PATHWAY SPECIFICALLY IT'S
DIFFERENT THAN A CHANNEL
MODULATOR ENHANCING TRAFFICKING
OR ENHANCING ENGAGEMENT IN CFTR.
THE ADVANTAGE OF A GENE ADDITION
IS IT WILL CORRECT ALL MUTATIONS
BUT THE DISADVANTAGE REGARDLESS
OF THE DISEASE YOU HAVE TO KNOW
THE PATHOPHYSIOLOGY AND TARGET
OF YOUR PROTEIN TO ANSWER THE
QUESTION AND SEE IF IT'S ONLY
NOW BEGINNING TO GET TO THE
POINT WHERE ANSWERS ARE BECOMING
CLEAR ON THAT.
THE CFTR KNOCKING IN A GENE
EDITING APPROACH KNOCK IN A
LARGE AXONS FOR INTERON AND
EVERYTHING DOWN STREAM IS A
UNIVERSAL APPROACH TO GENE
THERAPY TO TARGET MULTIPLE
MUTATIONS.
>> MAYBE BUILDING ON THAT FOR
ONE SECOND THINKING ABOUT THE
WAY YOU'RE TRYING TO THERAP
THERAPEUTICALLY APPROACH THE
DISEASE AND A SHORT SWORD AND
SHIELD MENTALITY BUT YOU MAY
HAVE A TOXIC GAIN OF FUNCTION
FROM THE VARIANT AND YOU NEED TO
FIND A WAY TO KNOCK THAT DOWN IN
COMBINATION WITH HOPEFULLY
EXPRESSING OR GETTING THE
ENDOGENOUS PROTEIN THERE WHETHER
IT'S A TRANSPORTER OR OTHERWISE
TO FUNCTION CORRECTLY.
THERE'S DIFFERENT WAYS AND
DIFFERENT SOLUTIONS TO THE
PROBLEM.
YOU CAN APPRECIATE IF YOU START
TAKING A DOUBLE APPROACH WHERE
YOU NEED TO KNOCK DOWN AND OVER
EXPRESS, THAT'S EFFECTIVELY LIKE
TWO DRUG DEVELOPMENT PROGRAMS
WRAPPED INTO ONE.
WE -- IT CAN GET COMPLICATED
FAST AND ADDS TO THE COMPLEXITY
OF IT.
I THINK THIS IS WHERE MODELS
LIKE ALFRED AND KRISTIN TALKED
ABOUT ARE SO IMPORTANT RATHER
THAN TACKLING THE TOTALITY OF
EVERYTHING IN AN IN VIVO MODEL
PARS THEM OUT AND ASK TARGETED
QUESTIONS THE IN VIVO MODELS AND
BUILD THAT BACK UP TO, LOOK, I
THINK THIS IS THE RIGHT SOLUTION
FOR THIS DISEASE.
>> OKAY.
I WILL GO AHEAD AND ASK THE NEXT
QUESTION.
SO ARE WE LEARNING ANYTHING FROM
THE LUNG CANCER DRUG DEVELOPMENT
COMMUNITY?
GRANTED THE PATHOPHYSIOLOGY IS
DIFFERENT BUT IMAGINE THERE ARE
SIMILAR ISSUES WITH MODELS TO
TEST THAT DON'T ADEQUATELY
REPRESENT HUMAN DISEASE.
SO ANY THOUGHTS ON CANCER
MODELS?
>> THAT'S A TOUGH ONE.
CYSTIC FIBROSIS.
THERE'S A LOT OF BIOLOGY WHEN WE
THINK OF STEM CELLS THAT
REGENERATE THERE'S A LOT OF
BIOLOGY SIMILAR TO CANCER THAT'S
GONE AWRY.
AND IN THE PULMONARY FIBROSIS I
TALKED ABOUT THE FIBROBLASTS ARE
SECRETING MOLECULES THAT ARE
DRIVING DYSPLASTIC REPAIR AND
REGENERATION OF AIRWAY
CONDUCTING CELLS IN THE AIR
SPACE.
IT'S ALL ABOUT COMMUNICATION
REPAIR AND RESOLVE OF AN INJURY
RESPONSE AND IN THE DISEASES
VERY CHRONIC SOME PROCESSES ARE
RELATED TO PATHWAYS THAT GO AWRY
IN CANCER AND CROSS GENETIC
SPACE IN CANCER OR GENETIC OR
CHRONIC DISEASE IN THE LUNG.
>> WE'RE MODELLING FIBROSIS AND
WE SEE THAT AS JUST THE
PRELIMINARY PROCESSES BEFORE
LUNG CANCER DEVELOPMENT.
AND I THINK WE'RE STARTING TO
WANT TO BE ABLE TO MODEL THAT
THE PROGRESSION FROM FIBROSIS ON
A CHIP AND I AGREE THERE SHOULD
BE MORE COLLABORATION BETWEEN
THE FIELDS AND I HOPE WE CAN SEE
THAT.
>> THERE MAY ALSO BE OPPORTUNITY
TO LOOK AT SOME OF THE
COMPENSATORY CHANGES THAT HAPPEN
IN THE ONCOGENIC STATE.
WE TALKED ABOUT A NUMBER OF
TRANSPORTERS THAT ARE ASSOCIATED
WITH DIFFERENT DISEASES AS WELL.
WE CERTAINLY KNOW FROM A
MULTI-DRUG RESISTANT STANDPOINT
MANY ARE UPRENREGULATED SPACE I
THE TRANSPORTERS THEY ARE PLAY
COME INTO PLAY FROM A MULTI-DRUG
RESISTANT STANDPOINT.
THAT'S NOT MY AREA OF EXPERTISE
BUT I CAN SEE THE WHERE THE
LEARNINGS IN THE BIOLOGY
ULTIMATELY NEED TO BE ADDRESSED
IN THE LUNG CANCER SPACE TOO.
>> I HAVE A QUESTION FOR THE
PANEL.
IT'S LISTENING TO THE DISCUSSION
IT BRINGS TO THE FORE ONE OF MY
CONCERNS AROUND THE IN VITRO
MODEL IS WE CAN'T ADEQUATELY
MODEL THE EXTRA CELLULAR SPACE
WITH THE MILIEU THE DRUG
ENCOUNTERS WHEN IT'S BEING
ADMINISTERED AND BRINGS TO MIND
THE CONCERNS AROUND CAN TO TO
BETTER MODEL THAT AND THE SECOND
QUESTION IN THE SESSION IS MAYBE
MORE DIRECTED TO JOHN IF WE ARE
THINKING THAT THERE'S A
REGENERATIVE ASPECT OF THIS AND
WE'RE LOOKING AT A DISEASE THE
CELLULAR ENVIRONMENT OF THAT IS
NOT REALLY GOING TO BE SIMILAR
TO WHAT WE'RE LOOKING AT IN A
DISH AND IN AND MAY BE CELLULAR
DAMAGE AND HOW DO YOU SEE
REGENERATION WHEN WE DELIVER OR
GENE, OUR DRUGS, ARE WE THINKING
THAT SOME OF THE EFFECTS NOT
NECESSARILY EVEN ON THE CELLS
ACTIVELY PARTICIPATING UP
SECRETION BUT PERHAPS PERHAPS IF
WE INTRODUCE OUR BASAL CELLS AND
LAG TIME AND HAVE GENERATION OF
LUNG AND THEN GOING TO SEE THE
EFFECTS.
CAN YOU COMMENT ON ANY OF THOSE
SOMEWHAT RANDOM QUESTIONS?
>> THERE'S A LOT TO UNPACK
THERE.
GETTING TO YOUR FIRST QUESTION
IS HOW CAN YOU PREDICT WHAT IS
GOING TO BE MOST RELEVANT IN
VIVO AND I'D SAY YOU CAN'T
ALWAYS PREDICT.
YOU START WITH -- WE TALKED
ABOUT KRISTIN'S MODEL IN VITRO
ON A CHIP MODEL IS INTRIGUING.
SAY YOU HAVE A SMALL DRUG AND
YOU DO SOME PRELIMINARY STABLES
IN VIVO AND CROSS THE
VASCULATURE AND HOW TO IMPROVE
THE PERMEABILITY START WITH A
MODEL THAT IS EASY LIKE IN VITRO
OR EASIER THAN DOING A LOT OF
ANIMALS IN VITRO ON A CHIP AND
CAN SCREEN AND UNDERSTAND THE
CHEMISTRY THAT NEEDS TO BE
CHANGED AND THEN GO IN VIVO AND
ASK SPECIFIC QUESTIONS ON A
SUBSET OF WHAT YOU MIGHT HAVE
SCREENED WHETHER OR NOT THE
BIOLOGY IS RETAINED WHEN YOU
ACROSS TO IN VIVO.
THE SECOND QUESTION ABOUT
PROGENITOR CELLS, CERTAINLY ANY
REMODELLED ORGAN IS GOING TO BE
MORE DIFFICULT TO FROM A GENE
THERAPY STANDPOINT.
IF YOU'RE TARGETING BASAL CELLS
YOU NEED A GEN EDITING APPROACH.
IF YOU TAKE A VIRUS YOU STICK IT
IN AND BASAL CELL REGENERATES
AND DIVIDES THE VIRUS UNLESS
IT'S INTEGRATED IS GOING TO BE
DILUTED AS THE REGENERATIVE
PROCESS GOES ON.
HAVE YOU THE INTEGRATOR AND EDIT
THE MUTANT GENE.
AND REPAIRING THE REMODELLED
LUNG OR WHATEVER YOUR TARGET IS
WILL BE A LONGER PROCESS SOME
WON'T REPAIR FROM MODELLING BUT
FROM A GENE EDITING STANDPOINT
THAT'S THE WAY TO GET THE CARGO
TO THE RIGHT PLACE AND YOU TA
YOU CAN ABOUT BASAL CELLS AS
BEING THE TARGET IT'S PROBABLY
1% OF BASAL CELLS ARE REALLY THE
ULTIMATE STEM CELL WILL PERSIST
FOR THE LIFE OF AN INDIVIDUAL.
>> THANK YOU ALL.
THANK YOU TO THE PANEL FOR
SHARING THEIR EXPERT OPINION AND
SHARING THEIR EXCITING RESEARCH
WITH US.
I THINK WE'LL COME TO OUR LUNCH
BREAK AND COME BACK AT 12:45 FOR
THE NEXT SESSION.
THANK YOU ALL.
>> HELLO AND THANK YOU ALL FOR
COMING BACK.
WE ARE GOING TO START THE SECOND
SESSION OF TODAY WHICH IS
PARTNERING WITH REGULATORS FOR
SUCCESSION AND NOW TO
DR. MOFFITT.
>> IF THIS IMPORTANT WAS
FOCUSSED TO DEVELOPING YOUR
ASSETS TO HAVE THE PHARMACOLOGY
AND SAFETY PROFILE, THIS
AFTERNOON IS MORE FACING
OUTWARDLY.
HOW DO YOU INTERACT WITH
REGULATORS?
WHAT ARE THE EXPECTATIONS YOU
HAVE FOR YOUR PROGRAMS AND HOW
DO YOU NAVIGATE THAT PROCESS
WHETHER YOU HAVE THE DRUG ABOUT
ITSELF OR WORK TOGETHER WITH A
DEVICE TO DELIVER THAT DRUG OR
EVEN HAVE COMPANION DIAGNOSTICS
YOU CAN THINK OF.
THERE'S REGULATORY COMPONENTS.
WE'LL HEAR A LITTLE BIT ABOUT
THE OVER ALL REGULATORY PROCESS.
IN ADDITION WE'LL HEAR HOW YOU
MARKET YOUR PROGRAM.
ESSENTIALLY WORKING WITH YOUR
OWN INTERNAL PROGRAMS AND MAKE
THE PACKAGE THAT LOOKS LIKE
SOMETHING LIKE VENTURE CAPITAL
OR PHARMA TECH COMPANIES MAY BE
INTERESTED IN AROUND IP AND
OTHER CONSIDERATIONS.
FINALLY, WE'LL TALK ABOUT
GOVERNMENT REGULATORY MECHANISMS
THERE TO HELP INCENTIVIZE
BUSINESS DEVELOPMENT AND GUIDE
FOLKS THROUGH THE PROCESS GOING
TO FORWARD.
SO, I THINK IT'S GOING TO TO BE
A REALLY INTERESTING TALK ABOUT
THE NEXT PHASE OF DRUG
DEVELOPMENT AS YOU'RE TRYING TO
GET THE WORD OUT AND INTERFACE
WITH THE EXTERNAL WORLD.
THE FIRST SPEAKER IS DR. MOODY
DIRECTOR OF REGULATORY AFARDZ
-- AFFAIRS IN RTI AND WORKED IN
NON-CLINICAL AREAS AND CMC AND A
WEALTH OF ADVICE COMING FROM HER
TODAY AROUND HOW TO NAVIGATE
THAT REGULATORY PROCESS.
SECOND SPEAKER IS KEVIN
WHITTLESEY AN EXPERT IN ALL
PHASES.
HE'S WORKED FOR THE FDA AND
WORKED FOR A COMPANY GETTING
ASSETS PAST THE IND STAGE INTO
DEVELOPMENT AND FINALLY HE'S
BEEN A CONSULTANT FOR A NUMBER
OF YEARLY YEARS PARTNERING WITH
COMPANIES SMALL AND LARGE TO
HELP THEM ADVANCE THEIR PRODUCTS
GOING FORWARD.
NEXT WE HAVE DR. CLARK AT THE
UNIVERSITY OF KENTUCKY WORKING
TO DEVELOP THERAPEUTIC
PORTFOLIOS FOR FOLKS WITHIN THAT
ORGANIZATION AND DEVELOP
BUSINESS MODELS AROUND HOW TO
EXTERNALIZE THESE NEW
TECHNOLOGIES.
DR. STEPHANIE DAVIS IS A SMALL
BUSINESS PROGRAM COORDINATOR AT
NHLBI.
SHE'S BEEN IN THIS ROLE A NUMBER
OF YEARS NOW AND HAD FORMALLY
BEEN A POSTDOC AND IS A TRAINING
BY SCIENTIST.
SHE HAD INTERNED AT THE
UNIVERSITY OF KENTUCKY PROGRAM
AS WELL TOO.
SHE'LL BE SHARING SOME OF HER
GUIDANCE AND INSIGHT AND FINALLY
DR. MIKE PECK WHO IS DIRECTOR OF
THE NHLBI CATALYZE PROGRAM AND
WILL WALK US THROUGH KEY
ACTIVITIES TO LEVERAGE AND THINK
ABOUT TO TRANSLATE OUR IDEAS
INTO A COMMERCIAL OPPORTUNITY
AND LEVERAGE THE GOVERNMENT
OPPORTUNITIES THERE.
WITH THAT I'LL TURN IT OVER TO
DR. MOODY.
>> GOOD AFTERNOON.
THANK YOU SO MUCH FOR JOINING
US.
I'M GOING TO TO BE TALKING ABOUT
HOW TO PREPARE FOR PRE-IND
MIDDLEWEIGHT THE FIRST MEETING
YOU HAVE DURING DEVELOPMENT AND
THEN GO INTO THE IND.
THE BIG QUESTION IS WHY DO I
NEED A PRE-IND OR INTERACT
MEETING WITH THE FDA.
THE ANSWER IS YOU DO NOT NEED TO
HAVE ONE.
THEY'RE NOT MANDATORY BY ANY
MEANS BUT IT'S A GOOD IDEA
ESPECIALLY IF YOU HAVE A NEW
MOLECULAR ENTITY ORE A DRUG NOT
PREVIOUSLY APPROVED TO TWO TO
THE REVIEW TEAM AND GET TARGETED
ADVICE TO HELP YOU DEVELOP YOUR
PRODUCT AND AVOID COSTLY
MISTAKES.
AGAIN, JUST TO ESTABLISH A
RAPPORT AND TRUST WITH THE FDA
REVIEW DIVISION.
THE FDA GIVES A SPECIFIC
PERSPECTIVE ON THE BENEFITS OF A
PRE-IND MEETING.
AND ONE OF THE MAIN THINGS THEY
TELL YOU IS IT MIN MIEDZS --
MINIMIZES THE POTENTIAL FOR
CLINICAL HOLD.
WHAT THAT DOES IS IT GIVES YOU
THE OPPORTUNITY AGAIN TO GO OVER
THE BASICS OF ALL THREE OF YOUR
BASIC PROGRAMS AND DISCUSS WITH
THEM WHERE YOU ARE AND WHAT
SAFETY YOU'LL BE PRESENTING AND
IT WILL HELP MINIMIZE COST,
AVOID UNNECESSARY STUDIES, AS
WELL AS MANY OTHER THINGS.
WHAT IS A PRE-IND MEETING?
IT'S A MEETING CALLED A TYPE B
MEETING.
IT'S A FORMAL MEETING WITH THE
FDA.
ONCE YOU REQUEST THE MEETING THE
FDA WILL SCHEDULE THAT MEETING
WITHIN 60 DAYS OF THE MEETING
REQUEST.
YOU'LL HAVE TO SUBMIT A BRIEFING
DOCUMENT THAT PROVIDES THE
QUESTIONS YOU WANT TO DISCUSS
AND SUPPORTING INFORMATION TO
GIVE THE FDA GUIDANCE ABOUT
ANSWERING QUESTIONS.
IT'S GREAT TO HAVE A PLAN FOR A
PRE-IND MEETING BEFORE THE IND
SUBMISSION.
THIS GIVES YOU A CHANCE TO GET
THINGS INFLATION -- IN PLACE IF
YOU NEED TO.
IT'S GOOD TO HAVE PRELIMINARY
CONCEPT AND SAFETY STUDIES DONE.
WHEN YOU HAVE DEVELOPED YOUR
MANUFACTURING PROCESS YOU MAY
NOT BE IN GNP MANUFACTURING YET
BUT DEFINE THE MANUFACTURING
PROCESS AND BEFORE YOU'RE
DEFINITIVE GOP TOX STUDIES.
ONE OF THE MAIN THINGS THAT WILL
BE HELPFUL TO DISCUSS AT THE
PRE-IND MEETING IS HOW YOU PLAN
TO RUN THE GLP MEETINGS AND HOW
THEY SUPPORT YOUR PHASE I
PROTOCOL.
WHAT TOPIC SHOULD BE DISCUSSED
SALT THE PRE-IND MEETING?
IT'S ABOUT THE DESIGN AND
DURATION OF THE GLP TOX STUDIES.
ISSUES WITH WITH YOUR CMC AND
DEVELOPING COMPARABILITY STUDIES
OR ANY SPECIFIC MANUFACTURING
ISSUES YOU HAD CAN DISCUSS
THEM -- WELL, YOU NEED TO HAVE
YOUR PROTOCOL SYNOPSIS OR
PROTOCOL AND WE RECOMMEND YOU
HAVE A DRAFT PROTOCOL IN YOUR
BRIEFING DOCUMENT FOR YOUR FIRST
IN MAN STUDIES.
AND DISCUSS YOUR REGIMENT AND
DEVELOPMENT CHALLENGES YOU HAVE
AND REALLY GO OVER ANY TOPICS
THAT THERE'S NO REALLY AN FDA
GUIDANCE FOR.
AN INTERACT MEETING CAN OCCUR
BEFORE THE PRE IND MEETING.
IT'S A NEWER FORMAL MEETING THE
FDA ESTABLISHED.
AND BASICALLY THE INTERACT
MEETING IS SCHEDULED 75 DAYS
BEFORE THE MEETING.
ONCE YOU SUBMIT THE MEETING
REQUEST AND THE IMPORTANT POINT
IS YOU'RE BRIEFING BOOK OR YOUR
MEETING PACKAGE BACKGROUND NEEDS
TO BE SUBMITTED WITH THE MEETING
REQUEST.
SO WHEN DO YOU HAVE YOUR
INTERACT MEETING?
IT'S EARLY IN THE DEVELOPMENT.
USUALLY AFTER YOU HAVE YOUR
COMPOUND IDENTIFIED, YOU'VE GOT
PRE CLINICAL PROOF OF CONCEPT OR
PILOT DATA AND AGAIN YOU HAVEN'T
DONE YOUR DEFINITIVE TOX STUDIES
BUT MAYBE YOU HAVE SOME ANIMAL
STUDIES IMPORTANT TO DISCUSS AND
AGAIN MANUFACTURING PLAN
STRATEGY FOR GOING FORWARD.
AGAIN, WHAT SHOULD BE DISCUSSED?
NOVEL PROGRAMS AND IT'S VERY
IMPORTANT TO DISCUSS YOUR
PRECLINICAL MODELS, THE
APPROPRIATE PRECLINICAL MODELS
OR THE TOXICOLOGY STUDIES FOR
NOVEL PRODUCTS.
CMC REQUIREMENTS AND ANY
SPECIFIC PLANS THAT YOU HAVE TO
DEMONSTRATE PRODUCT SAFETY.
YOUR PROOF OF CONCEPT STUDY
DESIGN.
YOUR RECOMMENDATIONS ABOUT THE
FIRST IN HUMAN TRIAL.
USUALLY THAT'S NOT SOMETHING YOU
SPEND AS MUCH TIME ON IN AN
INTERACT MEETING.
BUT ANYTHING THAT IF YOU WANT TO
USE ANY DATA COMING FROM OUTSIDE
THE U.S. YOU DISCUSS IT WITH THE
AGENCY.
AND YOU DON'T HAVE TO ANSWER THE
IN THE CHAT BUT SHOULD YOU
SCHEDULE A PRE-IND MEETING WITH
FDA AS EARLY IN DEVELOPMENT AS
POSSIBLE AND PEOPLE THINK IT'S
TRUE BUT IT'S FALSE.
YOU WANT TO SCHEDULE YOUR P
PRE-IND MEETING AND PROOF OF
CONCEPT AND A YEAR BEFORE YOU'RE
PLANNING TO FILE YOUR IND.
IT'S REALLY IMPORTANT WHEN YOU
GO TO THE FDA ABOUT HOW YOU ASK
YOUR QUESTIONS AND THE FDA --
YOUR FDA QUESTION SHOULD BE
HIGHLY SCRIPTED AND FORMAL.
HOW DO YOU ASK AN FDA QUESTION?
USUALLY QUESTIONS ARE TYPICALLY
YES OR NO QUESTIONS AND YOU
FRAME THEM AS DOES THE AGENCY
AGREE?
SO YOU PRESENT WHAT YOUR
STRATEGY IS AND THEN ASK THE FDA
IF THEY AGREE WITH YOUR
STRATEGY, IF THEY THINK IT'S
TRUE OR REASONABLE AND THE UNTO
ACT MEETING YOU CAN HAVE LESS
STRUCTURED QUESTIONS BUT FOR
YOUR PRE-IND YOU REALLY NEED FOR
THEM TO BE MORE STRUCTURED.
FREQUENTLY THE FDA'S GOING TO
SAY NO, WE DO NOT AGREE BUT
DON'T STRESS BECAUSE OFTEN TIMES
WHEN THEY DON'T AGREE -- NOT
OFTEN TIMES BUT THEY PROVIDE YOU
WITH ON WHY THEY DON'T AGREE AND
TRY TO MAKE SURE THEY UNDERSTAND
WHY THEY DON'T AGREE.
AND IF YOU DO CELEBRATE AND RUSH
TO THE NEXT THING.
AND YOU HAVE TO REMEMBER THE FDA
ARE NOT REGULATORY OR MANAGEMENT
CONSULTANTS.
YOU DO NOT GO TO THE FDA WITH
BROAD OPEN ENDED QUESTIONS LIKE
WHAT DOES THE FDA THINK OF OUR
DEVELOPMENT PLAN.
THAT'S WAY TOO BROAD AND WAY TOO
OPEN ENDED.
WHAT YOU WANT TO DO IS YOU WANT
TO SPEND TIME GOING THROUGH AND
WHAT SPECIFICALLY YOUR QUESTION
IS.
AND YOU CAN GET SPECIFIC
FOCUSSED INFORMATION ON YOUR
QUESTION.
BECAUSE IF YOU ASK A GENERAL
QUESTION YOUR LIKELY TO GET A
GENERAL RESPONSE OR LIKELY TO
GET A RESPONSE BASED ON THE
INFORMATION PROVIDED.
WE CAN'T ANSWER THIS QUESTION.
I RECOMMEND SPENDING A LOT OF
TIME THINKING ABOUT THE QUESTION
YOU WANT TO ASK.
AND LIMIT QUESTIONS IN YOUR MAIN
REQUEST TO TEN.
AN USE QUESTIONS TO REALLY ADD
THE NUMBER AND INCREASE THE
NUMBER OF QUESTIONS.
IF YOU HAVE A ONE-TIME INFORMAL
QUESTION, YOU CAN REACH OUT TO
YOUR REGULATORY PROJECT MANAGER
AND DISCUSS WHAT YOUR SPECIFIC
ISSUES ARE AND THE REGULATORY
PROJECT MANGE WILL GIVE YOU
ADVICE ABOUT WHETHER YOU NEED A
MEETING OR NOT.
AND ONE WEEK BEFORE THE MEETING
THE FDA WILL USUALLY SEND YOU A
PRELIMINARY RESPONSE, 24 TO 72
HOURS.
I SAY USUALLY BUT NOW IT'S
PRETTY MUCH ALL THE TIME.
THEY'RE GOING TO RESPOND TO YOUR
QUESTIONS IN THAT 24 TO 48 HOUR
TIME FRAME BEFORE THE MEETING.
AND USE THE PRELIMINARY
RESPONSES AND MAKE SURE THE FDA
ANSWERED THE QUESTIONS TO THE
POINT THAT THEY CAN UNDERSTAND
THE FDA'S POINT.
AND IF THEY STOP ANSWERING TOE
THIS TEAM'S SATISFACTION YOU CAN
CANCEL THE MEETING AND NOT HAVE
THE MEETING.
IF FURTHER CLARIFICATION IS
NEEDED FOR THE QUESTION USUALLY
OUT OF YOUR 10 YOU MAY HAVE
THREE OR FOUR QUESTIONS THAT
NEED FURTHER CLARIFICATION.
WHAT YOU WANT TO DO IS GET THAT
TO THE PROJECT MANAGER AND SAY
OUR TEAM IS INTERESTED IN HAVING
A DISCUSSION ABOUT 3, 5 AND 7
AND WANT NUMBER 7 TO BE THE
PRIORITY QUESTION TO DISCUSS.
AND HOLD A MOCK MEET AND HAVE
SOMEONE PLAY THE ROLE OF AN FDA
REVIEWER.
[NO AUDIO]
OR APPLICANTS.
IT'S AN MORE MEETING AND THE RPM
CHAIRS THE MEETING.
THE FIRST FIVE MINUTES ARE OR
INTRODUCTION TO THE FDA AND
SPONSOR.
NO LONGER IT USED TO BE WHEN I
FIRST GOT STARTED THE COMPANY
GAVE INFORMATION ON THE COMPANY
AND THINGS LIKE THAT NO LONGER
DO WE DO THAT AND WE HAD BASIC
INTRODUCTIONS AND THAT ALLOWS
FOR THE NEXT 50 MINUTES FOR
DISCUSSION OF THE QUESTIONS
AGAIN IN THE ORDER YOU NOTIFIED
THE RPM AS THE PRIORITY.
THE SUBJECT MATTER EXPERT CAN
GIVE A BRIEF EXPOSITION OR
BACKGROUND ON THE SPECIFIC
QUESTION.
USUALLY THAT'S THE MOST
INFORMATION OR EXPLANATORY
INFORMATION YOU'LL HAVE.
AND LIST OF PRIMARY QUESTIONS
FIRST THEN FIVE MINUTES BEFORE
THE MEETING ENDS IT'S A GOOD
IDEA FOR THE SPONSOR TO GIVE A
SUMMARY STATEMENT OF BASICALLY
THEIR UNDERSTANDING AND
TAKEAWAYS AND ACTION ITEMS.
AND AGAIN IT'S REALLY IMPORTANT
TO LISTEN AND TRY NOT TO ARGUE
WITH THE FDA.
AUTHOR EASY TO TALK TO IN MY
EXPERIENCE AND REALLY WANT TO
HELP YOU SO YOU NEED TO GO INTO
THE MEETING WITH THAT IDEA.
SO THE POST MEETING WRITE UP
YOUR MEETING MINUTES IMMEDIATELY
AFTER THE MEETING AND CIRCULATE
TO THE INTERNAL TEAM.
SO EVERYBODY ON THE TEAM SHOULD
BE TAKING NOTES WHILE THE
MEETING'S GOING ON.
YOU PUT YOUR NOTES TOGETHER AND
MAKE SURE THAT YOU ALL ARE
UNDERSTANDING WHAT YOU THINK
YOU'VE AGREED WITH THE FDA I
IT'S NOT THE FORM TO SEND THE
MEETING MINUTES BUT IT USED TO
BE AND THEY'LL SEND THEM 30 DAYS
WITHIN THE MEETING AND IT'S WEST
TO PUT YOUR TEAM TOGETHER,
REVIEW THE FDA'S INFORMATION
MAKE SURE THE INFORMATION THE
FDA PROVIDED IS RELEVANT AND
APPROPRIATE FOR WHAT YOU THINK
YOU DISCUSSED AND WHAT YOU
AGREED AND IF THERE'S ANYTHING
YOU THINK IS NOT APPROPRIATE OR
NOT EXACTLY RIGHT THE SPONSOR
CAN SUBMIT A REQUEST FOR
CLARIFICATION WITHIN 30 DAYS OF
THE RECEIPT OF THE MEETING AND
COME BACK TO YOU WITH RESPONSES
TO YOUR CLARIFICATION.
AND WE'LL PREPARE THE FDA SMICKS
WHAT'S AN IND?
AN IND IS A DOCUMENT YOU SUBMIT
TO THE AGENCY TO ALLOW YOU TO GO
INTO CLINICAL STUDIES.
THERE'S THREE MAIN PARTS TO THE
IND.
THE NON-CLINICAL INFORMATION,
WHICH IS THE RESULTS OF YOUR
PRE-CLINICAL DEVELOPMENT PROGRAM
INCLUDING YOUR GLP TOXICOLOGY
STUDIES.
THE OVER ALL GOAL OF THAT IS TO
ASSURE YOU HAVE ADEQUATE SAFETY
AND THE CHEMISTRY CONTROL WHICH
IS INFORMATION ON THE DETAILS OF
YOUR DRUG SUBSTANCE OR API SOME
CALL IT AND THE DRUG PRODUCT
MANUFACTURING.
YOU CAN MAKE AND TEST YOUR
PRODUCT USING GOOD MANUFACTURING
PRACTICE AND A BRIDGE BETWEEN
THE MATERIAL YOU USED IN YOUR
NON-CLINICAL GLP STUDIES TO THE
MATERIAL YOU'RE GOING TO USE IN
YOUR CLINICAL TRIALS.
IT DOESN'T HAVE TO BE EXACTLY
THE SAME BUT THE FDA WILL REVIEW
THE TATE FROM THE NON-CLINICAL
MATERIAL AND CLINICAL MATERIAL
TO MAKE SURE YOU HAVE COVERAGE.
INCLUDING THE PROTOCOL FOR THE
PHASE 1 CLINICAL TRIAL AND
INVESTIGATOR BROCHURE.
YOU NEED TO REASSURE THE FDA THE
PROPOSED STUDIES WILL BE SAFE,
THEY'RE SCIENTIFICALLY VALID AND
NOT EXCESSIVELY BURDENSOME AND
GOOD CONTENT AND FORMAT FOR THE
GUIDANCE DOCUMENT AND STILL VOLE
RANT AND APPROPRIATE NOW.
THERE'S AN INTRODUCTORY FORM OF
THE 1571 IN YOUR COVER LETTER.
THAT'S THE ADMINISTRATIVE
INFORMATION.
THEN YOU PROVIDE AN INTRODUCTORY
SUMMARY AND WHAT YOU WANT TO GET
ACROSS TO THE AGENCY.
THEN THERE'S THE GENERAL
INVESTIGATIONAL PLAN AND THAT'S
USUALLY ONE TO TWO PAGES AND THE
PURPOSE IS TO LET THE AGENCY
KNOW WHAT YOU'RE GOING TO DO.
NON CLINICALLY AND CLINICALLY
FROM THE NEXT YEAR REALLY.
PROVIDE YOUR PROTOCOL AND
STARTED SIX TO 12 MONTHS BEFORE
YOUR IND AND I LIKE TO INCLUDE A
DRAFT PROTOCOL IN THE PRE-IND
BRIEFING DOCUMENT BECAUSE THE
FDA VEEP FOR QUESTIONS, EVEN FOR
THINGS IRE IN YOUR PROTOCOL YOU
MAY NOT HAVE ASKED A QUESTION
OFTEN THE AGENCY NOTICES A FLAG
THEY'LL GIVE YOU ADVICE ON
SPECIFIC INFORMATION IN YOUR
PROTOCOL THAT MAYBE YOU DID NOT
HAVE THE QUESTION FOR THE PR
PRE-IND THEN YOU WANT THE
INVESTIGATOR'S BROCHURE AND
START THAT NINE MONTHS BEFORE
YOUR IND SUBMISSION AND IT'S
REALLY TO COVER IN SUMMARY FORM
THE INVESTIGATORS CAN UNDERSTAND
THE INFORMATION KWLUN CAL
INFORMATION YOU THINK IS
IMPORTANT FOR THE INVESTIGATOR
TO UNDERSTAND.
INCLUDE INVESTIGATOR ON THE DATA
ON FORM 1572 AND PRESENT THE CVs
OF YOUR INVESTIGATORS.
THE IND DATA AND PROVIDE AN IND
ROSTER SO THE AGENCY KNOWS WHO
THE IRB WAS THAT REVIEWED YOUR
CLINICAL PROTOCOL.
YOU CAN PROVIDE YOUR INFORMED
CONSENT IF THERE'S SOMETHING
SPECIFIC OR IF YOU HAVE A
DIFFICULT PROTOCOL OR PATIENT
POPULATION, YOU MAY WANT TO
INCLUDE YOUR INFORMED CONSENT
FORM AND ASK THE FDA FOR
FEEDBACK.
IF YOU DO A LITERATURE SEARCH IF
THERE'S RELEVANCE TO INCLUDE ANY
INFORMATION ON YOUR PRODUCT OR
VERY SIMILAR PRODUCTS.
YOU HAVE TO SUBMIT THE FORM 3674
SAYING YOU'LL REGISTER YOUR
STUDY WITH CLINICALTRIALS.gov.
MOST THE TIME YOUR PHASE I
PROTOCOL IS INCLUDED BUT LOOK AT
THE FORM AND MAKE SURE THAT
YOU'RE PHASE 1 IS EXCLUDED.
A RISK ASSESSMENT STATEMENT AND
BASIC INFORMATION ON LABELLING
AND INCLUDE THE COVER SHEET IF
IT'S RELEVANT BUT IT'S USUALLY
NOT NEEDED.
SO NOW FOR ALL COMMERCIAL
SUBMISSIONS, WHICH ARE MOST IND
SUBMISSIONS, THE IND HAS TO BE
SUBMITTED IN THE ELECTRONIC
COMMON DOCUMENT FORMAT.
THIS IS THE INFORMATION THERE'S
FIVE MODULES IN THE ECTD.
MODULE 1 IS ADMINISTRATIVE THE
COVER LETTER AND 1571 GOES AND
INTRODUCTORY STATEMENT AND
INVESTIGATOR BROCHURES AND
INCLUDES SUMMARIES FOR
NON-CLINICAL CMC AND CLINICAL
SUMMARY IF APPLICABLE BUT OFTEN
FOR PHASE I IT'S NOT AND MODULE
4 IS THE STUDY REPORT AND MODULE
5 ARE STUDY REPORTS.
IT'S IMPORTANT TO GET REGULATORY
ASSISTANCE NOW BECAUSE NOT ONLY
IS THERE SPECIFIC FORMAT FOR THE
ECTD YOU CAN GET WITH RTI AND WE
CAN HELP YOU.
WE'RE GOING TO TALK ABOUT
PROGRAMS FOR EXPIRED CONDITIONS
AND THERE'S FAST TRACK, WHICH IS
WHEN YOU HAVE NON-CLINICAL OR
CLINICAL DATA THAT POTENTIALLY
ADDRESS AN UNMET MEDICAL NEED.
ALSO WHEN YOUR PRODUCT'S BEEN
DESIGNATED AS A QUALIFIED
INFECTIOUS DISEASE PRODUCT.
YOU CAN SUBMIT AND THE PRE-IND
MEETING AND IT GRANTS YOU
ACTIACTION
S EXPEDITE ROLLING REVIEW WHICH
IS A REVIEW WHERE YOU SUBMIT
PORTIONS OF YOUR MARKETING
APPLICATION PERIODICALLY AND
THEN THERE'S BREAKTHROUGH AND
IT'S HARDER TO GET A
BREAKTHROUGH INDICATION.
IT'S WHERE YOU PRESENT
PRELIMINARY CLINICAL EVIDENCE
THAT DEMONSTRATES THIS IS
IMPORTANT -- THAT DEMONSTRATES
SUBSTANTIAL IMPROVEMENT ON A
CLINICALLY SIGNIFICANT END POINT
OVER AVAILABLE THERAPIES.
SUBMIT THE APPLICATION WITH OR
WITHOUT THE IND BUT BEFORE THE
END OF PHASE II AND GRANTS YOU
INTENSIVE GUIDANCE AND ROLLING
REVIEW.
SO SOME TALK HOME PEARLS, DO
ENGAGE THE TEAM EARLY AND
CONSIDER AN INTERACT MEETING AND
PRE-IND MEETING IF YOUR PRODUCT
IS NOVEL.
FOR ME FAMILIARIZE YOUR GUIDANCE
AND START NINE TO 12 MONTHS
BEFORE SUBMISSION AND EARLIER IF
YOU CAN.
DON'T ASK THE FDA OPEN ENDED
QUESTIONS.
ASSUME INTERACTIONS WITH THE FDA
ARE IN FORMAL.
TREATS THEM AS FORMAL.
HAVE YOUR QUESTIONS WORDED
APPROPRIA
APPROPRIATELY AND IT'S A BEST TO
KNOW THE ANSWERS NOW BEFORE YOUR
IND THAN IT IS TO GET TO YOUR
IND CLINICAL.
AND THERE'S DIFFERENT TYPES OF
FDA MEETINGS AND ABCD AND
INTERACT.
WE'RE NOT GOING TO GO THROUGH
THOSE.
THOSE ARE THE FORMAL MEETINGS.
WE CAN DISCUSS THOSE AT A LATER
POINT IN TIME.
AND HO DO YOU SUBMIT AN FDA
MEETING REQUEST?
WE'RE FOT GOING TO GO THROUGH
THE SPECIFICS OF THAT BUT IT'S
VERY SCRIPTED AND IN THE FORMAL
MEETINGS BETWEEN THE FDA
SPONSORS AND/OR APPLICANTS.
THE INFORMATION THAT GOES IN A
BRIEFLY BOOK YOU ASKED FOR A
TEMPLATE.
WE CAN PROVIDE YOU WITH ONE IF
YOU DON'T HAVE ONE.
THERE'S NO SPECIFIC FDA GUIDANCE
ON YOUR BRIEFING BOOK BUT WE CAN
PROVIDE YOU WITH FEEDBACK.
FINALIZE QUESTIONS.
THE BACKGROUND INFORMATION MEDED
FOR THE FDA TO ANSWER YOUR
QUESTIONS.
YOUR DATA SHOULD BE SUMMARIZED
AND SUCCINCT.
REMEMBER THEY HAVE I ASHORT
PERIOD OF TIME TO REVIEW YOUR
INFORMATION SO YOU WA IN THE TO
MAKE SURE IT'S SUMMARIZED AND
VERY SUCCINCT.
AGAIN, AFTER YOU SUBMIT YOUR
BRIEFING BOOK, YOU CANNOT
PROVIDE NEW INFORMATION TO THE
AGENCY DURING THE MEETING.
DON'T PANIC IT DOESN'T MEAN THE
FDA THINK THERE ARE MAJOR ISSUES
THEY ARE CAN'T ADDRESS IN THE
WRITTEN RESPONSE AND GIVEN THE
DETAILED WRIT ENRESPONSE --
WRITTEN RESPONSE AND THE SILVER
LINING IS YOU GET IT 30 DAYS
EARLIER FAN IF YOU HAD A FACE TO
FACE MEETING.
THE INFORMATION YOU PUT IN THE
PROTOCOL IS IN THE GUIDANCE
DOCUMENT BUT YOU PROVIDE THE
TITLE PAGE AND OBJECTIVES AND
STUDY DESIGN.
THE STUDY PROCEDURES AND YOUR
SAFETY REPORTING AND MONITORING
AND REPORTING YOUR STATISTICAL
ANALYSIS PLAN AND ETHICS AND
CONSIDERATIONS FOR QUALITY
ASSURANCE AND INFORMING ON DATA
MANAGEMENT AND MANAGING AND
AUDITING AND YOUR INFORMED
CONSENT IS OPTIONAL.
SO THE INFORMATION THAT GOES IN
THE TOP SECTION OF YOUR IND IS
THE DESCRIPTION OF THE
PHARMACOLOGIC EFFECTS AND
MECHANISMS OF THE ACTIONS IN
YOUR ANIMAL STUDIES AND DATA.
YOU INCLUDE AN INTEGRATED
SUMMARY OF YOUR TOXICOLOGY WHICH
IS A BRIEF DESCRIPTION OF THE
TRIALS AND ANY DEVIATIONS OR
ANYTHING LIKE THAT.
YOU PROVIDE A TOXICOLOGY FULL
TABULATION IS FOR EACH
TOXICOLOGY STUDY YOU PROVIDE A
FULL TABULATION OF THE DATA
SUITABLE FOR DETAILED REVIEW.
INFORMATION ON YOUR DRUG
SUBSTANCE.
IT'S THE CHEMICAL, PHYSICAL,
BIOLOGICAL CHARACTERISTICS AND
FLOW CHART FOR YOUR
MANUFACTURING PROCESS YOUR
LIMITS AND ANALYTICAL
SPECIFICATIONS YOU WANT TO
EXPERIENCE SUPPORT FROM YOUR
CDMO EARLY ON AND THE DRUG
PRODUCT INCLUDE THE COMPONENT
USED IN THE FORMERLATION.
THE QUANTITATIVE COMPOSITION AND
NAME AND ADDRESS AND
MANUFACTURING PROCESS AND
ACCEPTABLE LIMITS WITH
SPECIFICATIONS AND ANALYTICAL
METHOD.
INFORMATION ON THE STABILITY OF
THE DRUG PRODUCT AND PLACEBO IF
YOU'RE USING A PLACEBO.
>> AFTER YOU SUBMIT THE IND TOTE
FDA, FDA HAS 03 DAYS TO
ACKNOWLEDGE AND REVIEW RECEIPT
AND BEFORE THEY PUT YOU ON A
CLINICAL HOLD.
IF THEY DON'T HEAR FROM THE FDA
WITHIN 30 DAYS YOU CAN PROCEED
WITH YOUR STUDY, YOUR CLINICAL
STUDY.
IT'S BEST PRACTICE TO SAY IT'S
BEEN 30 DAYS AND AFTER THE 30
DAYS WITH COMMENTS AND YOU NEED
TO ACKNOWLEDGE.
AND WE HAVE A SHORT PERIOD OF
TIME AND SO ACCELERATED APPROVAL
AND PRIORITY REVIEW AND
ACCELERATE APPROVAL IS BASICALLY
A DRUG THAT PROVIDES THE
MEANINGFUL ADVANTAGE OF
AVAILABLE THERAPIES AND
DEMONSTRATE END POINT AND THAT'S
REALLY IMPORTANT AND ACCELERATED
APPROVAL AND 50USH8LY WITH
ONCOLOGY AND HIGH RISK, HIGH
REWARD AND POST APPROVAL YOU
HAVE TO VAL TATE THE SIR GAT END
POINT USED DURING DEVELOPMENT.
AND YOU NEED SUCH MONTHS RATHER
THAN A SOW MONTH REVIEW.
>> CARAMELA THANK YOU FOR THE
WONDERFUL OVERVIEW.
I THOUGHT IT WAS FANTASTIC.
A REMINDER TO FOLKS, PLEASE
UPLOAD QUESTIONS FOR CARAMELA IN
THE Q&A SECTION AND WE'LL COME
BACK TO THAT.
WITH THAT I'LL TURN IT OVER TO
DR. KEVIN WHITTLESEY.
>> THANK YOU FOR BEING HERE AND
THANKS FOR THE ORG -- ORGANIZER
AROUND CONSULTANT AND WORKED IN
PRODUCT DEVELOPMENT.
I WENT WANT TO TALK ABOUT
AEROSOL DEVELOPMENT AND IT'S
IMPORTANT CONSIDERATIONS AS A
PRODUCT FOR DELIVERY TO THE
AIRWAY.
AND IN SETTING YOURSELF UP AND
SHE GAVE A NICE OVERVIEW OF THE
AND TALK ABOUT THE DELIVERY
DEVICE CONSIDERATIONS AND HOW IT
INTEGRATES WITH THE EXPOSURE AND
MY PRIMARY SPACE IS IN GENE
THERAPIES.
THERE'S KEY DIFFERENCES I'LL
WORK ON HIGHLIGHTING.
SO THINKING ABOUT SOME OF THE
CONSIDERATIONS FOR AEROSOL
DEVELOPMENT IN TERMS OF THE
THERAPEUTIC MODALITIES SAY SMALL
MOLECULE DRUG AND GENE THERAPY
PRODUCTS OR OTHER BIOLOGICALS.
AND BY CONTRACT IN A GENES
THERAPY THE DEVELOPMENT
NECESSARY IN ENSURING AN
ACCURATE AND EFFECTIVE DOSE THE
ONUS IS HIGHER FOR GENE THERAPY
PRODUCT.
AND WE CONTRAST AND OTHER
BIOLOGICS CAN BE ADVERSELY
AFFECTED BY THE.
NEBULIZATION PROCESS AND MUST BE
TESTED.
AND REPEAT DOSE ON A WEEKLY OR
SOMETIMES DAILY BASIS AND FOR A
SINGLE ADMINISTRATION THE
PATIENTS ARE ABLE TO RECEIVING
ARE CRITICALLY IMPORTANT AND
ANYTHING THE FDA PUTS A LOT OF
EMPHASIS ON.
AND FINALLY COST IN THE SMALL
MOLECULES CANNOT BE MASS
PRODUCED IN LARGE QUANTITIES
EFFECTIVELY AND OTHER BIOLOGICS
CAN BE DIFFICULT AND EXPENSIVE
TO PRODUCE.
THE PRODUCT LOST DURING THE
AEROSOLIZATION PROCESS
ULTIMATELY BECOMES THE COST OF
THE PRODUCT IF YOU'RE MARKETING
THE PRODUCT.
IN THINKING OF SELECTION AND
IMPORTANT TO THINK THROUGH THE
RIGHT QUESTIONS IN TERMS OF
SELECTING THE DEVICE TO MOVE
FORWARD WITH.
FOR RESPIRATORY DISEASES ARE YOU
LOOKING TO TARGET MORE OF THE
UPPER AIRWAYS VERSUS THE LOWER
MORE DISTAL AIRWAYS?
AND SO WHAT IS YOUR TARGET SITE
FOR DEPOSITION NECESSARY FOR
YOUR ACTUAL THERAPEUTIC PRODUCT.
AND THEN WHAT TECHNOLOGY DO YOU
SELECT?
THE THREE CORE TECHNOLOGIES
INCORPORATED INTO JET NEBULIZER
AND VIBRATING MESH AND IT'S
IMPORTANT TO THINK ABOUT WHAT
TECHNOLOGY YOU'RE USING AND THE
SUITABILITY FOR YOUR PARTICULAR
DRUG PRODUCT.
FOR A FEW EXAMPLES JET
NEBULIZERS SUBJECT THE DRUG TO
NEB YOU'LL I'DATION FOR TIMES
OVER AND OVER WHICH CAN BE
DESTABILIZING AND INCREASE THE
RESERVOIR AFFECTING THE PRODUCT
OR IF THE PATIENT'S IMMUNE
RESPONSE AS THE CONCENTRATION OF
THE BUFFER SOLUTION INCREASES
AND LASTLY SHEER FORCES DIFFER
BETWEEN NEBULIZER AND MAY NEED
TO BE TESTED TO WHAT
TECHNOLOGIES ARE COMPATIBLE TO
THE THERAPEUTIC PRODUCT AND NEB
YOU'LLNEBULIZERS HAVE DIFFERENT
CAPACITIES DEPENDING ON HOW CON
OF CONCENTRATED THE SOLUTION AND
DEPENDS ON THE VOLUME
ADMINISTERED WHERE THERE'S
PATIENT COMPLIANCES THAT MAY
NEED TO BE INCLUDED.
TAKING THIS INTO THE
TECHNOLOGIES SHOWN AND ULTRA
SONIC VIBRATING MESH WHICH I'VE
REFERENCED AND THEY ARE HAVE
SLIGHTLY DIFFERENT REQUIREMENTS
IN TERMS OF THE CLINICAL SITE
ALL THREE REQUIRE ELECTRICITY
BUT A JET NEB YOU'LL I'DER
REQUIRE THE EXPRESSED SOURCE AND
SEEMS STRAIGHTFORWARD BUT
IMPORTANT TO UNDERSTAND MAYBE A
RARE DISEASE IN LESS DEVELOPED
AREAS WHERE THERE'S
INFRASTRUCTURE CHALLENGES AN
ENSURE YOU HAVE ACCESS TO THE
RESOURCES NECESSARY AT THE
INTENDED CLINICAL SITE.
AND THERE'S HETEROGENEITY AND
INDICATORS OF THE BOTTOM
RESERVOIR IS WHERE THE EXPRESSED
AIR SOURCE COMES IN AND THAT
THEN GENERATES THE VENTURI
EFFECT WHICH DRAWS FLUID FROM
THE SURFACE INTO THE AIR STREAM
THEN AEROSOLIZED.
THE BAFFLE IS WHERE LARGER
PARTICLES ARE DEFLECTED TO BE
RE-NEBULIZED IN THE EFFECT FOR
RE.
YOU'LLIZATION MANY TIMES IN THE
JET NEBULIZER.
THEY HAVE THE BROADEST RANGE OF
PARTICLE SIDES WITHIN THE
AEROSOL GENERATED.
THAT CAN BE TAILORED BASED ON A
NUMBER OF PROPERTIES BUT HAVE A
MORE DIVERSE RANGE BY CONTRAST
AND ULTRA SONIC HAVE MORE
CONSISTENT SIZED PARTICLES THAT
SIT AT THE BOTTOM OF THE
RESERVOIR AND GENERATES
ULTRASOUND AND AEROSOL ON THAT
AND THE VIBRATING MESH HAS A
PHYSICAL SCREEN WITH HOLES
PUNCHED IN IT AND THEY DEFINE
THE PARTICLE SIZE AND
SUBSEQUENTLY HAS THE SIZE
DISTRIBUTION OF THE SIZES.
AND IN TERMS OF THE ADDITIONAL
SHEER FORCES AND ULTRA SONIC
GENERATES HEAT IN THE REDS
VOYEUR AND NOT FOR THERMAL
PRODUCTS BECAUSE OF THE
SOLUTION.
VIBRATING MESH AND THE RESERVOIR
SITS OVER THE TOP AND THE
SOLUTION IS THEREFORE ONLY
NEBULIZED ONCE PASSING THROUGH
THE SCREEN WHICH MAY BE
ADVANTAGEOUS TO SOME PRODUCTS.
IN TERMS OF WHAT'S GOING ON IN
THE RESERVOIR, JET AND ULTRA
SONIC NEBULIZERS ARE SUBJECT TO
EVAPORATIVE LOSS IN THE SOLUTION
ACROSS THE VOLUME OF THE BOTTOM
AND THERE'S HIGH OSMOLALITY
CHANGE AND SEE DIFFERENCES IN
TERMS OF THE PRODUCT THAT'S
EXPENSIVE TO MANUFACTURING AND
JET AND ULTRA SONIC EXPERIENCE A
LOSS WHICH IS IN TERMS OF COST
OF GOODS AND WHAT THAT DOES IN
TERMS OF THE PROGRAM.
AND THERE'S IMPORTANT OSMALALITY
AND AFFECT THE AEROSOL.
IN THE CASE OF JET THE PARTICLE
SIZE AND DISTRIBUTION TO TARGET
THE AEROSOL YOU NEED TO CONSIDER
THESE OF THE THERAPEUTICS.
SO NOW IN THINKING IN TERMS OF
HOW YOU ARE GOING TO DELIVER
YOUR AEROSOL NON CLINICALLY.
THERE'S EXPOSURE SYSTEMS FOR
DIFFERENT ANIMALS AND ANIMAL
MELDS AND IN THE LEFT AND MIDDLE
ARE DELIVERY SYSTEMS FOR SMALL
ANIMAL FOR RODENTS.
WHAT YOU CAN APPRECIATE AND
INHALED THROUGH THEIR NESS AND
MOUTH.
THAT'S QUITE DIFFERENT FROM THE
WAY A PATIENT WILL EXPERIENCE
AEROSOL WHEREBY THEY'RE
TYPICALLY BREATHING OFF THE
MOUTH PIECE OF A NEBULIZER SO IN
THE CASE OF A SMALL ANIMAL
YOU'RE PRESENTING LESS MATERIAL
GOING TO INTO WHICH NEEDS TO BE
CONSIDERED.
AND THE NHP BREATHING THROUGH
BOTH THE NOSE AND THE MOUTH
LEADING TO POTENTIALLY MORE
PRODUCT BEING EXPOSED TO THE
UPPER FROM THE LOWER AIRWAYS
FROM THE CLINICAL SETTING.
IT NEEDS TO BE CONSIDERED IN
TERMS OF WHAT IMPACTS THE
DIFFERENCES MAY HAVE IN TERMS OF
THE SAFETY AND EFFICACY
ASSESSMENT.
AND THEY CAN BE USEFUL IN
DEMONSTRATE WITH EFFICACY AND
DELIVERY REPRESENTATIVE OF THE
CLINICAL SETTING IS DIFFICULT
AND DEMONSTRATING THEY'RE
INTENDED CLINICAL USE OF THE
PRODUCT.
WITH SMALL ANIMALS INHALATION
RESULTS IN THE LARGE FRACTION OF
THE DOSE IN THE UPPER AIRWAYS
WHICH MAY BE IMPACTFUL IN
ASSESSMENT OF SAFETY AND
EFFICACY IN THE MODEL.
AND A COMMON ROUTE OF
ADMINISTRATION IN MICE AND RATS
IS WHEREBY LIQUID IS DIRECTLY IN
THE TRACHEA AND GETS IN THE
LOWER AIRWAYS OPPOSED TO THE
NASAL INHALATION BUT CAN STILL
BE USEFUL IN DEMONSTRATION OF
EFFICACY OF THE PRODUCT.
IT'S AN DIFFERENCE BETWEEN THE
CLINICAL PRESENTATION THAT NEED
TO BE CONSIDERED AND
APPROPRIATELY JUSTIFIED TO THE
FDA.
LARGE ANIMALS ESPECIALLY LARGE
HUMAN PRIMATES DO NEED THE
CLINICAL DEVICE BUT THEY ARE
CANNOT BE TRAINED TO BREATHE
THROUGH A CLINICAL MOUTH PIECE
YOU HAVE TO USE THE PEDIATRIC
MASK WHICH ALSO RESULTS IN
SIGNIFICANT LOSS OF THE
DELIVERED DOSE AND DIFFERENT
PRESENTATION THAT WOULD BE USED
CLINICALLY AND ALTERNATIVE IS
THE ANIMALS CAN BE -- YOU CAN
DELIVER TO THE ANIMALS USING AN
ENDOTRACHEAL TUBE AND USE THE
DEVICE DELIVERED TO THE LOWER
AIRWAYS AND THESE ARE
ANESTHETIZED ANIMALS AN IT MAY
LEAD TO A DIFFERENT
UNDERSTANDING OF THE SAFETY AND
EFFICACY OF THE PRODUCT AND
DELIVERED DOSE.
THESE ARE REALLY IMPORTANT
QUESTIONS TO PUT FORWARD TO THE
FDA.
CARAMELA TOUCHED ON THIS IN
TERMS OF A PRE-IND QUESTION
SEEKING THE APPROPRIATENESS OF
AN ANIMAL MODEL AND SAY HERE'S
WHAT WE'RE THINKING.
WE UNDERSTAND THE DIFFERENCES
FROM OUR INTENDED CLINICAL USE
AND WHY WE THINK IT'S AN
APPROPRIATE MODEL AND DOES THE
FDA AGREE.
IT'S COMMON AND CAN BE A USEFUL
THING TO DO BEFORE YOU GO DOWN
THE WRONG PATH.
YOU WANTED TO TALK ABOUT
DELIVERY DEVICE TESTING.
IT'S IMPORTANT YOU CHARACTERIZE
YOUR PRODUCT AND ONE OF THE
POINTS I MENTIONED EARLIER ON
WAS ESPECIALLY WITH THE GENE
THERAPY PRODUCT AND LOOK AT THE
INTENDED DELIVERED DOSE IS.
THIS IS USUALLY DONE AS
EMPIRICAL LABORATORY BENCH
TESTING WITH YOUR AEROSOL IN
SOME CASES COUPLED TO IN VIVO
STUDIES AS WELL BUT SOME
CONSIDERATIONS INCORPORATED
FIRSTLY WHAT ARE THE PROPERTIES
OF THE AEROSOL AND KEY
PARAMETERS ASSESSED AND THE
DYNAMIC DIAMETER AND THE
STANDARD DEVIATION AND FRACTION.
THIS IS CHARACTERIZING THE
DISTRIBUTION OF SIZE PARTICLES
AND IF THEY NEED TONE LESS THAN
FIVE MICRONS TO BE INHALED IN
THE LUNGS AND WHAT FRACTION OF
YOUR PRODUCT IS WITHIN THE
RANGE.
ARE THERE CONCENTRATIONS
INSTABILITY OR BIOLOGICAL
STABILITY OF YOUR PRODUCT IN
TERMS OF STRAIGHT OUT OF THE
VIAL FROM THE MANUFACTURER
VERSUS GOING TO THROUGH THE
NEBULIZATION PROCESS AND
ASSESSED AND THAT'S AN IMPORTANT
ASPECT TO UNDERSTAND.
AND THE DELIVERED DOSE PRESENTED
TO THE PATIENT AIRWAY?
THE.
AND WHAT YOU'LL SEE IN THE CUP
OF THE NEBULIZER AND TYPICALLY
THE FDA ASKS TO COLLECT BENCH
TESTING DATA AND UNDER
WORST-CASE SCENARIO EXPECTED
DURING THE TRIAL AND IF
SOMETHING GOES WRONG DURING THE
ADMINISTRATION.
A FEW EXAMPLES MIGHT BE A THEY
ARE.
-- A DELAY AND THERE'S SOME
THEY ARE IN TERMS OF LOGISTICS
BEFORE THE PATIENT CAN START
TAKING THE NEBULIZED DOSE AND
HOW LONG CAN IT TAKE APPROPRIATE
CONCENTRATION AND ENSURE THERE'S
NO COMPATIBILITY ISSUES?
ADDITIONALLY, MAYBE THE PATIENT
IF IT'S RESPIRATORY DISEASE
PERHAPS THEY'LL EXPERIENCE A
PULMONARY EXACERBATION AND THE
CLINICIAN NEEDS TO INTERRUPT THE
NEB YOU'LL I'D -- NEBULIZER AND
RESUME DOES IT BEHAVE THE SAME?
YOU NEED TO UNDERSTAND BASED ON
THE PATIENT POPULATION WHAT ARE
THIS THINGS THAT CAN GO WRONG
AND DO WE NEED TO MODEL
NON-CLINICALLY AND ASSESS OUR
PRODUCT WILL PERFORM AS
EXPECTED?
SO THIS TOPIC OF TESTING IS
SOMETHING THAT IS APPROPRIATE TO
TALK ABOUT WITH THE FDA AS PART
OF THE PRE-IND MEETING AND LAID
OUT A CLEAR PLAN TO HEAR ALL THE
THINGS WE'RE PLANNING TO DO AND
HOW WE'RE PLANNING TO ASSESS
THEM AND DOES THE FDA AGREE IT
CHARACTERIZES THE AEROSOL FOR
OUR INTENDED TARGET POPULATION.
LAST THING I WANT TO TOUCH ON
ARE TO SHOW THE MEANS BY WHICH
THE ASSESSMENTS ARE CONDUCTED?
SO SHOWN ON THE LEFT IS A
CASCADE IMPACTER AND USED TO
CHARACTERIZE AEROSOLS.
YOU SEE ON THE OTHER SIDE OF THE
LID A SERIES OF SILVER METAL
SCREENS WITH INCREASINGLY FINE
MESH FROM LEFT TO RIGHT COARSEST
TO THE FINEST AND AEROSOLS FLOAT
IN ON THE LEFT AND FROM THE LEFT
SIDE AND AS THE AEROSOL GOES
THROUGH THE CLAIM BERS THE
PARTICLES OF THAT SIZE ARE
RETAINED AND CAN BE CAPTURED ON
FILTERS FOR SUBSEQUENT ANALYSIS.
IT'S AN ACTUAL PHYSICAL
COLLECTION AND DETERMINE HOW
MUCH OF YOUR PRODUCT ARE IN THE
SIZE RANGE PARTICLES WITHIN THE
CHAUM BERS.
AND WHAT PERCENTAGE TO
UNDERSTAND WHAT FRACTION OF YOUR
DOSE IS WITHIN THE AEROSOL AND
CHARACTERIZATION AND BY CONTRAST
IS THE TESTING SCHEME USING A
LASER DETECTION METHOD WHEREBY
YOU USE LASER TO MEASURE IN REAL
TIME THE DISTRIBUTION OF
PARTICLES GENERATED BY AN
AEROSOL.
IT'S MORE DIFFICULT TO COLLECT
BUT HIGH THROUGHPUT AND
ACCURATE.
THESE ARE TWO COMMON METHODS
USED TO CHARACTERIZE AEROSOLS IN
UNDERSTANDING WHAT IS YOUR
PRODUCT LOOKING LIKE AND HOW IS
IT PERFORMING.
TO WRAP UP A COUPLE KEY POINTS
IS SELECTION OF YOUR NEBULIZER
TECHNOLOGY IS IMPORTANT AND
NEEDS TON THE MOST APPROPRIATE
FOR YOUR TARGET INDICATION AND
FOR YOUR THERAPEUTIC PRODUCT AND
THAT'S INFLUENCED BY A NUMBER OF
CONSIDERATIONS.
ANIMAL MODELS EXHIBIT
SIGNIFICANT INDICATIONS FOR
AEROSOL DELIVERY AND IT'S
IMPORTANT TO UNDERSTAND WHAT
THEY ARE AND THINK ABOUT THE
APPROPRIATE SCIENTIFIC
JUSTIFICATION FOR UTILIZATION OF
THE RIGHT ANIMAL AND GET
AGREEMENT FROM THE FDA AROUND
YOUR RATIONALE AND ANIMAL MODELS
AS APPROPRIATE.
DETERMINE STARTING CLINICAL
DOSE TO ENSURE PATIENTS ARE
GOING TO SEE NOT ONLY SAFE BUT
EFFICACIOUS DOSE AND CONSIDER
DEVELOPMENT PLAN TIME LINE AND
WHEN TO SEEK INPUT ON YOUR PLAN
FROM THE FDA AND THANK YOU FOR
YOUR TAKES AND LOOK FORWARD TO
THE DISCUSSION.
>> THANK YOU.
A GREAT SUMMARY OF A DETAILED
APPROACH OVER YEARS OF
EXPERIENCE AND WORKING WITH
REGULATORS DIRECTLY.
IF THERE'S QUESTIONS FOR KEVIN
BEFORE YOU E-MAIL HIM PERSONALLY
ASK HIM IN YOUR DISCUSSION AT
THE END OF TODAY AND E-MAIL HIM
LATER.
NEXT UP IS DR. HOLLY CLARK
>> GOOD AFTERNOON MY NAME IS
HOLLY CLARK AND I'M U.K.
INNOVATE AT THE UNIVERSITY OF
KENTUCKY AND WE THINK AHEAD TO
MAKE A PRODUCT OR PATIENT FROM
YOUR INNOVATION.
AND YOU'VE HEARD A LOT OF VERY
VALUABLE INFORMING ABOUT THE
DRUG DEVELOPMENT PROCESS AND TOX
STUDIES AND REGULATORY MODELS
AND REQUIREMENTED AND MORE AND
TO HAVE THE NEW THERAPEUTIC EN
TORE FOR A NEW PATIENT YOU NEED
TO THINK OF THE
COMMERCIALIZATION PROCESS.
SO, IT'S ALSO OTHER WISE KNOWN
AS WHY AND WHEN TO CONTACT THE
TECHNOLOGY TRANSFER OFFICE.
THE FIRST QUESTION IS THE WHY.
I USE THE SLIDE WHEN I'M TALKING
TO FACULTY AND OTHER RESEARCHERS
ACROSS CAMPUS AND I HEAR I TO MY
RESEARCH AND I PUBLISH AND
PRESENT IT AND GO TO CONFERENCES
BUT WHY SHOULD I DO THIS
INTELLECTUAL PROPERTY
COMMERCIALIZATION THING?
PROTECTING YOUR INNOVATION IS
NECESSARY TO GET YOUR NEW
THERAPEUTIC TO A PATIENT.
OF COURSE THERE'S MUCH VALUE TO
YOUR UNIVERSITY OR RESEARCH
INSTITUTION AND THE INNOVATOR IN
THE PROCESS.
IT'S GETTING NEW UNIVERSITY OR
RESEARCH INNOVATIONS ON THE
MARKET.
NEW PRODUCTS TO IMPROVE QUALITY
OF LIFE FOR A PATIENT.
IF YOUR TALKING ABOUT STARTING A
COMPANY AND BUILDING LOCALLY
IT'S ECONOMIC DEVELOPMENT.
AND RESEARCH INSTITUTION THAT
HAS A ROBUST PROGRAM IN THIS
AREA CAN ATTRACT INNOVATIVE
FACULTY AND RETAIN STUDENTS AND
POSTTOCK.
WITH PROMOTE INDUSTRIAL
RELATIONS TO LICENSE NOVE RATION
AND SUPPORTING NEW RESEARCH AND
THE RIGS GOES TO THE PERSONAL
SIDE TO THE INNOVATORS.
PERSONAL SATISFACTION OF THE
DISCOVERY OF A PATIENT HELPING A
PATIENT.
I ALSO WANT TO MENTION MOST
INSTITUTIONS, IF NOT ALL, OUR
INSTITUTION AND OTHERS DO SHARE
LICENSE INCOME WITH INNOVATORS
DIRECTLY.
THERE'S VALUE IN KNOWING YOUR
INNOVATION GOT OUT THERE AND THE
INITIAL INNOVATION RAND
TECHNOLOGY TRANSFER PROCESS IS
SUMMED UP ON THE SLIDE.
FIRST, GIVE US A CALL.
TALK TO YOUR TECH TRANSFER
OFFICE.
SUBMIT A DESCRIPTION OF YOUR
INNOVATION THROUGH WHATEVER
PORTAL SYSTEM PROCESS YOU'RE
INSTITUTION USES.
WE HAVE AN ONLINE PROGRAM
PORTAL.
I USUAL HAVE A NOTE SAYING
BEFORE YOU PUBLISH OR PRESENT.
SO IF YOU'RE TAKING NOTES RIGHT
NOW, PLEASE WRITE DOWN CONTACT
MY TECH TRANSFER OFFICE BEFORE I
PRESENT AND YOU'LL SEE WHY IN A
FEW SLIDE.
THAT'S THE FIRST PART.
LET US KNOW ABOUT YOUR
INNOVATION.
AS SOON AS WE KNOW ABOUT YOUR
INNOVATION WE WELL LEARN MORE
AND LIKE TO SEE DATA AND LIKE TO
LEARN.
WE'LL THEN DO A PRETTY
MARKETABILITY ASSESSMENT TO SEE
HOW TO PROTECT THE INNOVATION
AND INTELLECTUAL PROPERTY.
WE'RE NONPROFIT AND NEED TO GO
FORWARD TO CREATE A NEW
THERAPEUTIC OR DRUG.
WE WANT TO PROTECT THE
INTELLECTUAL PROPERTY.
THIS SLIDE SUMMARIZES THE FOYER
PLAIN WAYS INTELLECTUAL PROPERTY
IS PROTECTED FOR RESEARCH
INSTITUTIONS.
WE FOCUS ON PATENT COPYRIGHT AND
TRADEMARK AND I PUT TRADE SECRET
TO THE SIDE BECAUSE THEY'RE
SECRET.
SOME ARE USED AND THEY'RE MEANT
TO BE CONFIDENT CONFIDENTIAL AND
THAT'S FOR FUNDING WHERE WE WANT
TO DISSEMINATE RESULTS BROADLY
TO THE PUBLIC.
WE DON'T TEND TO DO TRADE
SECRETS SO I'LL FOCUS ON PATENTS
AND WHAT DOES IT GET YOU IF YOU
HAVE AN ISSUED PATENT?
THE RIGHT TO EXCLUDE USING A
CLAIMED INVENTION FOR A
CERTAINLY PERIOD OF TIME, A 20
YEAR PERIOD AND TRANSLATES TO A
PERIOD OF EXCLUSIVITY.
I MENTIONED IT EXCLUDES OTHERS
BUT IT WAS SET UP TO ENCOURAGE
INNOVATION AND ENCOURAGES
THE DISCLOSURE OF KNOWLEDGE
BECAUSE PRAT ENTS ARE PUBLISHED
YOU CAN SEE THE LATEST AND EST
IN UPCOMING INNOVATIONS IN THE
FIELD AND HOW YOU MIGHT FURTHER
INNOVATE IN THE FIELD.
MOST IMPORTANTLY FOR THE
PURPOSES OF COMMERCIALIZATION
PATENTS PROTECTION INTELLECTUAL
PROPERTY PROTECTION IS USUALLY
THE BEST WAY TO BENEFIT THE
PUBLIC HEALTH BECAUSE OF THAT
RIGHT TO EXCLUDE OTHERS FROM
MAKING, AND SELLING.
THAT ABILITY SO EXCLUSIVITY AND
A COMPANY PARTNER IS GOING TO
WANT EXCLUSIVITY TO KNOW WHEN
THEY'RE PUTTING IN MILLIONS OF
DOLLARS TO DEVELOP A NEW
THERAPEUTIC, THERE'S AN A PERIOD
OF EXCLUSIVY.
VERY QUICKLY WHAT CAN BE PR
PATENTED?
RATE.
I'LL FOCUS ON THE SLIDE
COMPOSITIONAL MATTER YOUR NEW
THERAPEUTIC OR BIOLOGIC AND THE
NEW INNOVATION AND METHOD OF
TREATMENT.
YOU PLAY HAVE A NEW INNOVATION.
YOU MAY BE REPURPOSING A NEW
DRUG AND IT MIGHT BE REPURPOSING
A NEW DRUG FOR A NEW INDICATION.
IT WOULD BE A METHOD OF NEW
TREATMENT FOR A NEW DRUG.
I MENTIONED THE VAECHLT PROCESS
IN YOUR UNIVERSITY TECH TRANSFER
OFFICE.
IT'S IMPORTANT TO HAVE THEM
CONDUCT A VERY THOROUGH PATENT
ABILITY ASSESSMENT.
YOU CERTAINLY ARE EXPERTS IN
YOUR FIELD AND KNOW THE
LITERATURE.
BUT PUBLISHED PAPERS DO NOT
INCLUDE EVERYTHING MOST
COMPANIES DON'T PUBLISH ON THEIR
LEAD DRUG.
INSTEAD THEY CERTAINLY ARE GOING
TO PROTECT THEM.
SO TECH TRANSFER OFFICES WILL
SEARCH BOTH THE U.S. AND WORLD
WIDE PATENT DATA OFFICES AND
WHEN THEY FIND SOMETHING CLOSE
THEY'LL LET YOU KNOW.
WE ENGAGE THE INNOVATORS.
IT'S A TIME AND COST SAVING WITH
PAT IN THE PROSECUTION AND CAN
HELP US GUIDE THE INNOVATION AND
HOW THE CLAIMS WILL BE
STRUCTURED.
THE EARLIER THE BETTER.
THIS WILL BE A THEME OF MY TALK.
THE EARLIER THE BETTER YOU TALK
TO YOUR TECH TRANSFER OFFICE IS
THE BETTER.
GIVE YOUR TECH TRANSFER OFFICE
TIME TO CONDUCT A THOROUGH
ASSESSMENT.
WE'VE DONE AN ASSESSMENT AND IT
LOOKS LIKE WE'LL HAVE ROOM TO
GAIN CLAIMS AND LOOKS LIKE
THERE'S AN AREA WHAT WE FOUND IS
CERTAINLY NEW, USEFUL, OFFICE.
BECAUSE IT'S THE INVENTION MAY
BE PATENTABLE DOESN'T MEAN
ANYONE WILL PICK UP THE PRODUCT.
WE ALSO LOOK IN THE MARKET.
WHAT'S THE MARKET POTENTIAL AND
BETTER THAN WHAT IS OUT THERE
AND THIS IS SOMETHING THE TECH
TRANSFER OFFICE WILL WORK WITH
YOU ON.
THE THIRD PART OF THE ASSESSMENT
PROCESS IS THE COMMERCIALIZATION
PART.
AS I MENTIONED BEFORE, AND WE
DON'T PUT THINGS IN A BOTTLE AND
MARKET AND SELL TO THE PUBLIC
FOR PUBLIC HEALTH.
OUR GOAL IS TO HAVE THE
TECHNOLOGY DEVELOPED TO BENEFIT
THE PUBLIC AND TO FIND AN
INDUSTRY PARTNER TO HELP DEVELOP
THAT TECHNOLOGY.
THERE ARE MANY TIMES OF
COMMERCIALIZATION PATHWAYS THAT
CAN LEAD TO PARTNERSHIP.
LIKE I SAID IT MIGHT BE WE HAVE
A PARTNER THAT WANTS TO HELP
SPONSOR DEVELOPMENT OF A
TECHNOLOGY GOING FORWARD AND
RESEARCH IN A LAB.
LICENSING.
WE HAVE PROGRAMS THAT START NEW
COMPANIES.
THIS SLIDE TALKS ABOUT
COMMERCIALIZATION PATHWAYS
FINDING A COMMERCIALIZATION
PARTNER.
WHEN I STARTED IN TECH TRANSFER
FOR A NEW THERAPEUTIC THERE WERE
LICENSING TO ESTABLISH A COMPANY
AND POTENTIALLY STARTING A NEW
COMPANY.
THERE'S ADVANTAGES TO WORKING
WITH A BIG PHARMA OR ESTABLISHED
BIO TECH AND THEY'RE WELL FUNDED
AND BEEN THERE, DONE THAT.
THEY HAVE THE PROCESS ALREADY
THERE, HOWEVER, THERE ARE THINGS
TO CONSIDER.
I'VE HEARD FROM THE PARTNERS,
THE BIG PLAYERS IT'S AN
INTERESTING MECHANISM AND
INTRIGUING DATA BUT CALL US WHEN
IT'S IN PHASE II RAND IT'S HARD
TO GET THERE.
YOU MAY THINK I KNOW MY
TECHNOLOGY THE POST AND WILL
START A COMPANY.
OUR COMPANIES HAVE PROGRAMS TO
HELP AND HAVE ENTREPRENEURSHIP
TRAINING AND HELP WITH FUNDING
AND YOU'LL HEAR THE NEXT TALK IS
ABOUT SOME FUNDING IN THAT AREA
YOU NEED TO CONSIDER YOUR AND
STARTING A START UP PLAY BE
DIFFICULT FOR A ONE-PRODUCT TYPE
OF TECHNOLOGY OR MAYBE A SMALL
MARKET.
IT'S TIME.
IT'S FUNDING.
FUNDING -- THERE ARE CHALLENGES.
TIME AND FUNDING.
SO THINGS TO CONSIDER.
OVER THE PAST DECADE THOUGH A
NEW COMMERCIALIZATION PATH HAS
ARISEN WHICH IS GOOD FOR NEW
THERAPEUTIC TECHNOLOGIES.
AND IT'S THE VENTURE BUILDER OR
VENTURE STUDIO.
THESE ARE VENTURE CAPITAL
ACTUALLY STARTING NEW START UPS
BUT HAVE SAID, HMM, MAYBE WE CAN
REDUCE OUR RISK BY AN
INTERESTING ACADEMIC TECHNOLOGY
AND LICENSE IT AND BUILD THE
COMPANY FROM WITHIN BECAUSE WE
HAVE THE FUND AND CAN HAVE A
MANAGEMENT TEAM.
WE HAVE THE EXPERTISE.
AND THEY WORK WITH THE
INSTITUTION, WITH THEY ARE
LICENSE THE TECHNOLOGY, WORK
WITH THE INNOVATOR AND HELP
DEVELOP IT SO IT'S MORE
ATTRACTIVE FOR THE BIGGER
PLAYERS.
A PATENT EXCLUDE OTHERS FROM
USING AND SELLING AND LICENSE IT
THROUGH AN AGREEMENT.
IT'S A PERMISSION SLIP AND
IMPORT THE INVENTION.
THEY CAN BE EXCLUSIVE TO ONE
COMPANY OR NON-EXCLUSIVE IF YOU
HAVE A PLATFORM TECHNOLOGY AND
WANT TO HAVE SEVERAL LICENSEES
AND IT MAY BE NON-EXCLUSIVE.
THERE'S A LOT I CAN GET INTO
WITH HOW A LICENSE WORKS BUT THE
MAJOR BENEFITS TO DOING A
LICENSE IS YOU'RE FINDING A
PARTNER AND YOU'RE WORKING ONE A
PARTNER TO GET THE PRODUCT
DEVELOPED.
THERE MAY BE RESEARCH SHARED
RESOURCES AND MAY BE SPONSORED
RESEARCH A COMPANY MAY SAY WE'RE
GOING TO LICENSE THE TECHNOLOGY
AND SPONSOR RESEARCH IN THE LAB
TO DEVELOP IT FURTHER.
IN TERMS OF INCOME, THE
UNIVERSITY CAN RECOUP THE
INTELLECTUAL PROPERTY COST.
THERE MAY BE ROYALTIES OR OTHER
PAYMENTS FOR DEVELOPMENT.
THERE'S A LOT THAT CAN COME FROM
THE LICENSE OF AN INVENTION.
ANOTHER REASON TO CONTACT THE
TECH TRANSFER OFFICE WE DO A LOT
OF OTHER THINGS.
A LOT OF OTHER AGREEMENTS.
PROTECTING THE EXCHANGE OF
INFORMATION.
IT'S VERY IMPORTANT AMONG
RESEARCH INSTITUTIONS AND
COLLABORATORS TO SHARE DATA AND
INFORMATION AND MATERIALS AND WE
CAN HANDLE ALL THAT AGREEMENT TO
PROTECT YOU IN THAT SHARING.
WHEN THERE'S A JOINT TECHNOLOGY
WE WORK IT OUT WITH THE OTHER
COLLABORATING INSTITUTION TO
COME UP WITH AN AGREEMENT WHICH
SETS THE TERMS OF THE AGREEMENT
AND HOW A JOINT TECHNOLOGY
WESTBOUND -- WILL BE PROTECTED
AND COMMERCIALIZED.
COMING BACK TO WHEN SHOULD YOU
CONTACT MY TECH TRANSFER OFFICE?
EARLY.
WE LIKE TO SAY IT'S NEVER TOO
EARLY BEFORE YOU PUBLISH OR
PRESENT HOWEVER IT CAN BE TOO
LATE.
YOU WANT TO MAKE SURE YOU
PROTECT WORLDWIDE PATENT RIGHTS.
CONTACT US FOR TRANSFERS OF
MATERIALS, CONFIDENTIAL
INFORMATION, CONNECTIONS WITH
RESEARCHERS -- REGULATORY AND
OTHER PARTNERS.
I GET INNOVATORS WHO ARE WRITING
FUNDING OPPORTUNITIES, I WILL
MENTION A FEW IN A MOMENT AND
LETTERS OF MENTION, NEXT SLIDE,
PLEASE.
NEXT SLIDE, PLEASE.
VERY QUICKLY I WOULD LIKE TO
INTRODUCE YOU TO OUR OFFICE, UK
INNOVATE.
ACTUALLY NEXT SLIDE, GO,A HEAD.
-- GO,A HEAD.
WE ARE A BIT UNIQUE IN THAT ALL
AREAS OF COMMERCIALIZATION AND
ENTREPRENEURSHIP ARE LOCATED
UNDER 1 ROOF, THAT'S UKINNOVATE,
THE COMMERCIALIZATION PROCESS IS
UNDER OUR COMMERCIALIZATION
PILLAR.
OUR INNOVATION TRAINING AND
ENTREPRENEURSHIP TRAINING IS
UNDER OUR ECOSYSTEM PILLAR WHERE
WE HELP TEACH OUR INNOVATORS
ABOUT THIS PROCESS.
INNOVATION CONNECT IS OUR
INDUSTRY PARTNERSHIP'S GROUP.
THIS IS A GROWING AREA AND I'M
HAPPY TO SAY UK'S IN THE LEAD IN
THIS AREA AND INNOVATIONS THAT
HAVE SOCIETAL IMPACT AND EXIST
WITH AND FOR THE COMMUNITY FOR
THE PUBLIC BENEFIT AND NEXT
SLIDE, PLEASE.
AND JUST HIGHLIGHTING A FEW
PROGRAMS, I MENTIONED FUNDING,
UK IS PART OF THE MIDSOUTH HUB
WHICH IS A 4 STATE HUB FOR BOTH
NSF I-CORP AND RESEARCH AND
EVALUATION HUB.
IT'S A FUNDING PROGRAM FOCUSED
ON PRODUCT DEVELOPMENT.
WE HAVE OTHER PROGRAMS THAT ARE
ON THIS SLIDE, IN BLUE IS A
BRAND NEW, WE JUST ROLLED THAT
OUT.
IT'S A NEOF THE -- NETWORK AND
TRAINING FOR ANGEL INVESTORS TO
INVEST IN OUR START-UP
COMPANIES.
NEXT SLIDE, PLEASE.
WITH THAT, THANK YOU VERY MUCH.
ONCE AGAIN I'M HOLLI AND THIS IS
WHERE TO FIND ME.
>> HOLLY, THANKS SO MUCH IF ARE
THAT WONDERFUL TALK.
WORKING WITH TECH TRANSFER
OFFICES, I CAN UNDERSCORE HOW
IMPORTANT IT IS THAT INDUSTRY
LOVES TO WORK WITH FOLKS THAT
ARE REALLY ORGANIZED, HAVE THEIR
ACTS TOGETHER AND KNOW EXACTLY
HOW TO COMMUNICATE WITH US
BECAUSE OF WHAT WE'RE LOOKING
FOR, SO THANKS FOR THAT GREAT
OVERVIEW THEY THINK REALLY
CAPTURES IT.
THANK YOU.
ALL RIGHT, SO NEXT UP IS
DR. STEPHANIE DAVIS.
>> THANK YOU JEFF.
IF YOU COULD ADVANCE TO THE NEXT
SLIDE.
I WILL TRY TO ZIP THROUGH THESE
WITH MY COLLEAGUE DR. MIKE PECK,
NEXT SLIDE, THERE WE GO.
SO WE'RE GOING TO BE COVERING 2
PROGRAMS THAT CAN HELP FUND
TRANSLATIONAL TECHNOLOGIES IN
THE HEART, LUNG, BLOOD AND SLEEP
SPACE.
I WILL TALK ABOUT THE SMALL
BUSINESS, ALSO KNOWN AS THE
SBIR/STTR PROGRAMS AND DR. PECK
WILL COVER CATALYZE.
SO WE WILL NEXT THIS EFFICIENT.
NEXT SLIDE, PLEASE.
THERE WE GO.
SO IT WAS A GREAT THING THAT
DR. CLARK WENT BEFORE US
BECAUSE, YOU KNOW IF YOU ARE AN
ACADEMIC RESEARCHER YOUR TECH
TRANSFER OFFICE WILL BE A GREAT
RESOURCE FOR ANYTHING HAVE TO DO
FOR APPLYING FOR SMALL BUSINESS
FUNDING.
SO FOR THOSE WHO ARE UNFAMILIAR
WITH THE PROGRAMS, THE SBIR, TCR
PROGRAMS MAKE UP THE AMERICA'S
SEED FUND OR THE SMALL BUSINESS
PROGRAM.
AT THE NIH WE SET ASIDE 1.4
BILLION DOLLARS TOWARDS FUNDING
EARLY STAGE TECHNOLOGIES THAT
CAN HELP ADVANCE THE MISSION OF
THE NIH.
OH, GO BACK.
THANK YOU.
SO THESE PROGRAMS CONSIST OF THE
SMALL BUSINESS INNOVATION
RESEARCH, OR SBIR, WHICH THE IS
PARENT PROGRAM AND THIS IS
DESIGNED TO SUPPORT SMALL
BUSINESS CONCERNS THAT ARE
DEVELOPING NEW TECHNOLOGIES FOR
THE POTENTIAL FOR COMMERCIAL
ARIZATION, AND THE SISTER
PROGRAM, THE STTR PROGRAM.
THIS IS VERY SIMILAR TO THE
SBIR, WITH 1 MAJOR DIFFERENCE IN
TERMS OF ITS GOAL AND THAT IS TO
FACILITATE PARTNERSHIPS BETWEEN
ACADEMIC INSTITUTIONS AND SMALL
BUSINESSES.
OKAY.
JUST GO TO THE NEXT SLIDE.
THERE WE G. BOTH OF THESE
PROGRAMS HAVE A SIMILAR GOAL.
AND THROUGH BOTH OF THESE
PROGRAMS, THE NHIERARCHIES H IS
STAGED AS THE EARLY CAPITAL FOR
STAGES IN THE U.S., SO RO-1,
R23S, OTHER BASIC GRANTS TEND TO
FUND SMALL BUSINESS SCIENCE,
SMALL BUSINESS FUNDS WILL FUND
EVERYTHING FROM EARLY STAGE,
PROOF OF CONCEPT, TECHNOLOGICAL
DEVELOPMENT ALL THE WAY UP TO
SCALE AND MANUFACTURING.
AND WE ARE THERE TO FUND THESE
INNOVATIONS WHEN PRIVATE
INVESTORS SUCH AS ANGEL
INVESTORS, VC TIRMS AND PART
MERS ARE NOT TO RISK TOO MUCH.
SO OUR GOAL IS TO RISK ENOUGH
THAT THEY ARE ATTRACTED FOR
THESE PRIVATE INVESTORS.
WHEN YOU APPLY FOR AN NIH GRANT,
IT'S NONDILUTIVE, WE'RE NOT
TAKING MONEY OUT OF YOUR COMPANY
AND IT'S A LOAN THAT YOU DON'T
HAVE TO PAY BACK.
AND WHEN YOU GET THESE GRANTS
YOU HAVE TO GO THROUGH THE
RIGOROUS PEER REVIEW PROCESS AS
YOU WOULD WITH ANYTHING ELSE AT
THE NIH.
NEXT SLIDE, PLEASE.
SO AS I MENTIONED THE SMALL
BUSINESS PROGRAMS ARE MADE UP OF
SBIR AND STTR GRANTS AND THEY
ARE MORE SIMILAR THAN THEY ARE
DIFFERENT BUT THERE ARE A FEW
KEY DIFFERENCES.
SO SBIR GRANTS DON'T REQUIRE
PARTNERING WITH BUT THEY CAN
ALLOW FOR PARTNERING TO OCCUR,
THERE ARE GUIDELINES WHERE FOR
EARLY STAGE GRANTS ALSO KNOWN AS
PHASE 1S ISSUES THE COMPANY CAN
OUTSOURCE UP TO 33% OF THE
BUDGET AND 50% OF THE BUDGET IN
PHASE 2 AND THERE IS A
REQUIREMENT FOR AN SBIR ON THE
GRANT TO BE PRIMARILY EMPLOYED
BY THE BUSINESS AT THE TIME OF
THE AWARD.
SO THE STTR, IT'S THE PRIME
OPTION FOR EARLY STAGE ACADEMIC
SPIN-OUTS A-BECAUSE THERE'S A
REQUIREMENT TO HAVE A RESEARCH
INSTITUTION PARTNER WITH THE
SMALL BUSINESS THAT THAT
RESEARCH INSTITUTION AND PARTNER
WILL BE A SMALL ORDER RECIPIENT.
THERE ARE MINIMUM WORK
REQUIREMENTS OR BUDGET
REQUIREMENTS FOR BOTH THE SMALL
BUSINESS AND RESEARCH
INSTITUTION PARTNER AND MOST
IMPORTANTLY, THE PI CAN BE
EMPLOYED EITHER BY THE RESEARCH
INSTITUTION OR BY THE SMALL
BUSINESS.
SO IF YOU'RE A FULL-TIME FACULTY
MEMBER WITH A COMPANY, STTR A
GREAT OPTION FOR YOU BUT IN BOTH
CASES THE AWARD IS MADE TO SMALL
BUSINESSES.
NEXT SLIDE.
SO THERE ARE ELIGIBILITY
CRITERIA THAT NEED TO BE MADE
THROUGH THE TIME OF THEARS WARDS
BUT IN SUMMARY IN ORDER FOR YOUR
COMPANY TO BE ELIGIBLE FOR A
GRANT, IT MUST BE ORGANIZE AS A
U.S. BUSINESS, SMALLER THAN 500
EMPLOYEES, ALTHOUGH MOST OF THE
COMPANIES WE FUND ARE MUCH
SMALLER THAN THIS AND THE WORK
ON THE PROJECT MUST BE DONE
WITHIN THE U.S. WITH A FEW VERY
CASE BY CASE EXEMPTIONS.
SO THE COMPANY MUST BE AT LEAST
50% U.S. OWNED AND INDEPENDENTLY
OPERATED SO KEEP IN MIND ALL
THESE THINGS NEED TO BE MET AT
THE TIME OF THE AWARD, BUT DUE
TO THE SBIR AND STTR POLICY
DIRECTIVE, ALL ORGANIZATIONS
THAT RECEIVE GRANTS NEED TO
ADHERE TO THIS CRITERIA.
NEXT SLIDE, PLEASE.
SO AS I MENTIONED THERE ARE
DIFFERENT PHASES OF SMALL
BUSINESS GRANTS AND THESE ARE
NOT THE SAME AS CLINICAL TRIAL
PHASES.
THEY HAVE SAID THEY REFER TO
STAGE OF DEVELOP.
SO EARLY STAGE INVESTIGATORS
TEND TO COME IN WITH A PHASE 1
GRANT AND THIS IS A SMALL GRANT
THAT SUPPORTS PROOF OF CONCEPT
WORK, USUALLY IT'S AROUND
$314,000 TOTAL COSTS, AND
BETWEEN 1 AND 2 YEARS IN LENGTH.
AND ONCE THE PHASE 1 IS DONE,
THE COMPANY CAN APPLY FOR A
PHASE 2 GRANT WHICH SUPPORTS
MORE EFFICACY ORIENTED WORK AND
MORE EXTENSIVE R&D ACTIVITIES
COMPARED TO THE PHASE 1.
SO THESE GRANTS CAN BE BETWEEN 1
AND 3 YEARS LONG AND USUALLY
THEY'RE A LITTLE BIT OVER
$2 MILLION TOTAL COST.
THERE ARE ADDITIONAL OPTIONS, SO
IF A COMPANY WANTS TO APPLY FOR
BOTH THE PHASE 1 AND PHASE 2
SIMULTANEOUSLY, THEY CAN DO IT
FAST TRACK AND ALSO FOR SBIR
APPLICANTS, IF A COMPANY HAS
ALREADY DONE WHAT WOULD AMOUNT
TO A PHASE 1 GRANT, THEY CAN DO
A DIRECT TO PHASE 2.
AND SOME INSTITUTES AND CENTERS
INCLUDING THE NHLBI OFFER
ADDITIONAL FUNDING OPPORTUNITIES
BEYOND THE PHASE 2.
HOWEVER, WE DON'T HAVE PHASE 3
AWARDS.
SOME AGENCIES WILL ACCESS THESE
WHERE THE BUYER ACCESSES THE
INFORMATION, WE DON'T DO THAT.
WE HAVE THE IDEA THAT BEYOND
THESE FUNDING OPPORTUNITIES THE
COMPANY WILL BE SUPPORTED BY A
STRATEGIC PARTNER OR SUPPORTED
BY PRIVATE FUNDS AND WON'T NEED
US ANYMORE.
NEXT SLIDE.
SO I RECOMMEND IN ANYBODY HAS
QUESTIONS ABOUT PUTTING TOGETHER
AN APPLICATION, THE NIH SEED
OFFICE WEBSITE HAS A LOT OF
REALLY GREAT RESOURCES AND THESE
INCLUDE THE SF424 APPLICATION
MANUEL FOR SMALL BUSINESS
GRANTS, ANTIINFORM SET AND
SAMPLE APPLICATIONS FROM REAL
LIFE SMALL BUSINESS GRANTEES.
I ALSO RECOMMEND THAT YOU LOOK
THROUGH STATE RESOURCES, THROUGH
THE SBA FAST PROGRAM, AND OTHER
RESOURCES THAT HOLLY SHOUTED OUT
TO IN HER PRESENTATION, IF YOU
HAVE ANY NIH FUNDED ACADEMIC
PROOF OF CONCEPT PROGRAMS, SUCH
AS THE REACH PROGRAM, WHICH RUNS
THE MIDSOUTH HUB, I WOULD
STRONGLY RECOMMEND TAKE 8
HOURSING ADVANTAGE OF THOSE TO
HELP MAKE YOURSELF MORE
COMPETITIVE.
NEXT SLIDE, PLEASE.
>> SO THE NHLBI SMALL BUSINESS
PROGRAM, WE HAVE APPROXIMATELY
$136 MILLION EVERY YEAR IN
NONDILUTED FUNDING TO SUPPORT
OVER 300 ACTIVE PROJECTS THAT
ARE MEANT TO PREVENT, TREAT AND
DIAGNOSE LUNG DISEASES, SO AS
YOU SEE BY THIS PIE CHART WE
HAVE A LOT OF TECHNOLOGIES WE
FUND AND THIS BREAK DOWN VARIES
FROM YEAR TO YEAR BUT ABOUT 33%
OF OUR PORTFOLIO CONSISTS OF
THERAPEUTICS BOTH SMALL
MOLECULES AND BIOLOGICS.
NEXT SLIDE, PLEASE.
SO HERE IS JUST A BRIEF SAMPLING
OF DISEASES THAT FALL WITHIN THE
NHLBI MISSION SPACE. THIS IS
NOT AN EXHAUSTIVE LIST THOUGH SO
IF YOU HAVE A CONDITION THAT'S
NOT LISTED HERE AND YOU'RE NOT
SURE WHETHER IT'S WITH OUR
MISSIONS BASE, WE STRONGLY
RECOMMEND REACHING OUT TO US
FIRST AND IF IT DOESN'T WORK
WITH US, WE CAN DIRECT YOU TO
THE INSTITUTION OR BEST FIT.
SO I WILL NOT GO INTO ALL THE
DETAILTHIS SLIDE BUT THIS
PROVIDES A BRIEF SUMMARY OF WHAT
MY OFFICE, THE INNOVATION AND
COMMERCIALIZATION OFFICE DOES SO
OUR OFFICE PROVIDES SUPPORT IN
THE FORM OF APPLICATION SERVICES
SO THIS CAN INCLUDE OUTREACH AND
EDUCATION EVENTS, PREAPPLICATION
CONSULTS, AND ASSISTANCE
PROGRAMS TO HELP COMPANIES
BECOME COMPETITIVE APPLICANTS.
WE OFFER SMALL BUSINESS GRANTS,
PHASE 1 AND PHASE 2 AND
ADDITIONAL FUNDING BEYOND PHASE
2 AND FOR AWARDEES THEY HAVE A
LOT OF DIFFERENT RESOURCES THEY
CAN TAKE ADVANTAGE OF FOR THEIR
PRODUCT DEVELOPMENT JOURNEY.
SO THESE CAN INCLUDE CONSULTS
FROM OUR PART-TIME ENTREPRENEUR
AND RESIDENT WHO IS CAN PROVIDE
FEEDBACK IN AREAS SUCH AS
INTELLECTUAL PROPERTY,
REGULATORY AFFAIRS,
REIMBURSEMENT, HEALTH ECONOMICS
CLINICAL TRIALS AND FUNDRAISING
AND THESE EE Rs HELP US PUT ON
WEBINARS AND EDUCATIONAL EVENTS.
SO WE HAVE ADDITIONAL
ADMINISTRATIVE SUPPLEMENTS SUCH
AS RECRUITING NEW TALENT TO
ENHANCE THE DIVERSITY OF THE
PROGRAM, WE HAVE A SPECIAL
DIVERSITY SUPPLEMENT PROGRAM
SPECIFICALLY FOR SMALL BUSINESS
GRANTS.
WE SUPPORT COMPANIES THROUGH THE
ICHOR PROGRAM WHICH HELPS WITH
DORPHY, WE PROVIDE TECHNICAL AND
BUSINESS ASSISTANCE RELATED
ACTIVITIES AND BEYOND THE PHASE
2 WE OFFER SPECIAL AWARDS
THROUGH THE COMMERCIALIZATION
READINESS PILOT, AWARD PROGRAM.
WE ALSO HAVE A LOT OF NEW
ACTIVITIES, WE'RE DOING AS PART
OF OUR INVESTOR INITIATIVES.
SO THIS CAN INCLUDE COMPANIES TO
PRESENT AT SHOWCASE EVENTS WHERE
THEY'RE COACHED BY OUR EIR TEAM
SO THEY CAN PUT TOGETHER A GREAT
PRESENTATION THAT ATTRACTS
INVESTORS IN ATTENDANCE, WE HAVE
ALSO RECENTLY DEVELOPED AN AI
POWERED PARTNERING PLATFORM TO
BETTER HELP OUR AWARDYS CONNECT
WITH POTENTIAL INVESTORS AND
COLLABORATORS AND STRATEGIC
PARTNERS.
NEXT SLIDE, PLEASE.
HERE IS THE TARGETING
OPPORTUNITIES THAT THE NHLBI
FOCUSES ON, MOST OF THESE COME
IN AS OMNIBUS SOLICITATIONS BUT
THERE ARE A FEW SELECTED
OPPORTUNITIES THAT HAVE SPECIAL
DUE DATES OR SPECIAL REVIEW
CRITERIA OR IN SOME CASES SET
ASIDE FUNDS.
SO HERE'S EXAMPLES OF SPECIAL
FUNDING OPPORTUNITY WE SUPPORT,
SO WE HAVE OUR SPECIAL PHASE 2
IIB-BRIDGE AND SMALL MARKET
RFAs WHICH PROVIDE FUNDING FOR
COMMERCIALIZATION, THE
COMMERCIALIZATION PILOT
READINESS AWARDS WHICH CAN
PROVIDE UP TO $500,000 IN
EXPANSE PENSS TO SUPPORT LATE
STAGE RND AND TECHNICAL
ASSISTANCE.
FOR COMPANIES DEVELOPING
TECHNOLOGYINGS FOCUSED ON PANE
MANAGEMENT WE PARTICIPATE IN THE
HEAL INITIATIVE RFAs, TODAY WE
SUPPORTED 3 PROJECTS TOTAL 2 OF
WHICH FOCUSED ON PROJECTS IN THE
LUNG DISEASES MISSION SPACE.
IF YOU'RE DEVELOPING ANYTHING
FOCUSED ON HEALTH DISPARITIES OR
TREATING MINORITY HEALTH
PATIENTS WITH HEART, LUNG, BLOOD
AND SLEEP DISORDERS, WE STRONGLY
RECOMMEND LIVING INTO THE
HEALTHY LIVING RNA AND FINALLY
WE HAVE 4 NOTICES OF FUNDING
OPPORTUNITY THAT SERVE AS AN
OMNIBUS SET FOR OUR NEW
ENTREPRENEURS AND EARLY STAGE
INVESTIGATORS WHO WANT TO SERVE
AS PIs ON SMALL BUSINESS
GRANTS.
NEXT SLIDE, PLEASE.
AND EACH IF YOU'RE NOT APPLYING
FOR THE OPPORTUNITIES AND GOING
THROUGH THE OMNIBUS, WE
RECOMMEND LOOKING AT THIS FOR
PRIORITIZING HIGH AREAS OF
SCIENTIFIC ACTIVITY.
YOU CAN PUT OMNIBUS BUT IF PUT
THE NOCI IN THE PAGE 4, YOU CAN
GET THE APPLICATION TAGGED AS
BEING A PRIORITY AREA, SO HAVE
YOU A PROPOSAL THAT RELATES TO 1
OF THESE NOCIs, WE RECOMMEND
APPLYING THROUGH IT.
NEXT SLIDE, PLEASE.
ALL RIGHT AND SO IF YOU HAVE ANY
QUESTIONS OR WANT TO FIND OUT
ANYTHING ABOUT THE SMALL
BUSINESS PROGRAM AND
COMMERCIALIZATION OFFICE, I
RECOMMEND FOLLOWING US ON X,
VISITING OUR WEBSITE OR IF HAVE
YOU ANY QUESTIONS YOU CAN REACH
OUT TO US AT NHLBISCOAR
SBIR@MAIL.NIH .GOV.
AND WITH THAT I WILL TURN IT
OVER TO MY COLLEAGUE DR. PECK TO
DISCUSS CATALYZE.
>> I THINK I AM THE LAST SPEAKER
IF THIS SESSION SO I WILL TRY TO
BE SUCCINCT.
SO WE TOLD YOU ABOUT THE
SBIR/STTR, WHERE YOU HAVE TO
HAVE A SMALL BUSINESS TO APPLY,
CATALYZE SUPPORTS ALL U.S. BASED
ORGANIZATIONS, FOR PROFIT,
NONPROFIT.
PREACADEMIC, ALL OF IT.
SO WE'RE TAKING A SLIGHTLY
DIFFERENT APPROACH THAN THE SBIR
AND OTHER FUNDING PROGRAMS AT
THE NHLBI, SO INSTEAD OF GIVING
YOU MONEY AND FINDING ONCE A
YEAR, WE BECOME A PARTNER AND
EXTENSION OF YOUR TEAM THROUGH
OUR RECORDING CENTER AND HELP
YOU ACHIEVE WHAT YOU'RE TRYING
TO DO OR LET THE TECHNOLOGY FAIL
WITH WRAP AROUND SUPPORT WITH
EXPERTS AND REALLY 3 KEY AREAS,
EXPERTISE WHEN YOU NEED IT IN
TECHNICAL AND BUSINESS, AS
CARMEN MENTIONED THERE'S A
REGULATORY PART THAT COMES WITH
THE PROGRAM, AND VALIDATION OFF
THE BASIC RO-1 OR R35 AWARD, ALL
THE WAY UP TO MAYBE IN BETWEEN
SBIR PHASE 2, AND 2 A PHASE 2 B,
FOR THE STUDIES.
NEXT SLIDE, PLEASE.
AND WE'RE REALLY HERE FOR THE
ENTIRE NHLBI COMMUNITY, SO HEART
LUNG, BLOOD, SLEEP AND 5
DIFFERENT TRACTS OF TECHNOLOGY,
I GUESS MOST RELEVANT TO THIS
TALK WOULD BE THE FIRST 2 ROWS
OF THE THERAPEUTICS BUT THEN
ALSO WE DO HAVE SOME COME IN FOR
ENABLING TECHNOLOGY AND
TRANSFORMATIVE PLATFORMS I WILL
WALK YOU THROUGH AND AGAINOT
LEFT SIDE ARE WHAT WE FOUND
THROUGH, WHAT WE CALL THE
PRODUCT DEFINITION, GRANT
FUNDING PROGRAM AND ON THE RIGHT
SIDE OF THE BLUE, THE
PRECLINICAL WE HAVE A STAND
ALONE PRECLINICAL SERVICES
PROGRAM TO SUPPORT TARGETED
ACTIVITIES IN THIS BUCKET TO GET
YOU TO THE FDA, TO
[INDISCERNIBLE].
NEXT SLIDE.
SO WE HAVE SUITE AS A STAND
ALONE TECHNOLOGY, AND
INFORMATIVE PLATFORM, AND PHASE
2, WE HAVE GENE THERAPY TEAM FOR
DEVELOPING NEW TARGETING
VEHICLES FOR THE TEAM DELIVERY
FOR EXAMPLE, IN THE MIDDLE, THIS
TALK OR THE SMALL MOLECULE
BIOLOGICS SO WE HAVE A BI-PHASIC
R33 AND THIS IS FOR SMALL
MOLECULES, BIOLOGICS, GENE
THERAPY AND ALSO THIS NEW THIS
YEAR AND NEW IN ROUND ARE FOR
ACCOMMODATION PROD UBTS THAT
HAVE A COMPONENT AND THEN FOR A
SLIGHTLY LATER STAGE PROJECTS WE
HAVE A STAND ALONE R33 PROGRAM.
ALL OF THE DIRECT COSTS ARE
LISTED HERE AND AGAIN THE MAIN
DIFFERENTIATOR BETWEEN THIS
PROGRAM AND WHAT WAS MENTIONED
IS THAT WE DON'T HAVE THE SAME
PERCENT REQUIREMENTS OR THE
ORGANIZE IEGZ REQUIREMENTS OF
THE SMALL BUSINESS PROGRAM
REQUIRES AND WE DO ALLOW YOU TO
OUTSOURCE MUCH OF YOUR WORK IF
IT'S JUSTIFIED TO CONTRACT
ORGANIZATIONS.
NEXT SLIDE, PLEASE.
SO BAKED INTO THESE PROJECTS ARE
A FOCUS ON PROJECT MANAGEMENT,
MILESTONES AND TIMELINES AND THE
IMPORTANCE OF HOLLY MENTIONED
INTELLECTUAL PROPERTY BUT THEN
ALSO A FOCUS EVEN AT THE
APPLICATION STAGE THAT YOU MUST
HAVE SOME SORT OF REGULATORY
STRATEGY, DEVELOPED AND THAT
COULD BE AS BASIC AS WE WILL GO,
THIS IS A DRUG THAT HAS TO GET
AN IND AND IF YOU HAVE A MORE
MATURE PROJECT, WE HAVE TO HAVE
MORE DETAIL ABOUT WHAT THAT
ENTAILS.
FOR THE R33, WE HAVE A MATCHING
FUNDS EXECATION AS WELL AS
ACRAILTOR PARTNER AND AGAIN THE
KENTUCKY ORGANIZATION WOULD BE
AN EXAMPLE OF AN ACCELERATOR
PARTNER AND THE GOAL OF THIS IS
TO KIND OF HELP ACADEMIC
INVESTIGATORS CHANGE THEIR FOCUS
FROM THAT RO-1 HYPOTHESIS DRIVEN
RESEARCH TO NOW, WORK TOWARD
PRODUCT DEVELOPMENT AND GETTING
THEM FOCUSED ON ACCELERATING
THIS PROJECT TO BECOME A
THERAPY.
NEXT SLIDE.
SO IN ADDITION TO THE GRANT
FINISHED BE SITE, WE ARE A
PRECLINICAL SERVICES PROGRAM
WITH YOU APPLY THROUGH OUR
CODING CENTER, RTI, FOR A MORE
TARGETED POINT TO GET YOU TO
AIAN POINT TO FINALIZE YOUR YOUR
IND OR GET YOU DATA TO THEN
APPLY FOR AN SPWITH IRPHASE 2
AND REALLY WHERE THE ENTRY POINT
OF THIS IS FOR THE DRUG OF
THERAPEUTICS IS, YOU MAY NOT
HAVE HAD YOUR PREIND YET BUT YOU
SHOULD HAVE ALL YOUR DATA TO
SUPPORT A PREIND AND WE CAN
SUPPORT THE PREIND THROUGH OUR
REGULATORY SERVICES AND THEN
ONCE THAT'S COMPLETE, WE WILL
INVEST IN THOSE SCALE TO THE GMP
QUALITY MATERIALS FOR THE IND
ENABLING TECHNOLOGIES.
AND AGAIN WE'RE NOT SUPPORTING
THE ENTIRE PRECLINICAL PROGRAM,
WE COME IN AND IDENTIFY KEY
ACTIVITIES THAT WILL MAKE YOUR
-- DERISK YOUR TECHNOLOGY AND
MAKING IT MORE COMPETITIVE FOR
TRADITIONAL GRANT FUNDING OR IF
YOU HAVE AN INVESTOR IN MIND WHO
NEEDS TO SEE CERTAIN DATA IN
ORDER TO INVEST, WE ALSO
EVALUATE THOSE TYPE OF
APPLICATIONS, TOO.
NEXT SLIDE.
GREAT SO THIS A PARTNERSHIP
BETWEEN MYSELF, AND I SIT ACROSS
ALL THE DIVISIONS OF THE NHLBI
ISSUES THE PROGRAMMATICS SUBJECT
MATTER EXPERT WITHIN THE NHLBI
AND THEN WE ALSO HAVE STEF AND
HER TEAM IN THE INNOVATION
OFFICE SUPPORT THESE
INVESTIGATORS AND THIS IS WITHIN
PARTNERSHIP WITH THE
COORDINATING CENTER, THE RTI
WHICH HAS THE INFRASTRUCTURE TO
SUPPORT A BROADER ARRAY OF
TECHNOLOGY TYPES.
SO WE CAN GO TO THE NEXT LIED.
AND REALLY THIS IS A TEAM OF
EXPERTS, EACH TEAM IS ASSIGNED,
A PROGRAM MANAGER, OR A EXPERT
AND THEN HAVE YOU ACCESS WHEN
YOU NEED IT, AND THEN ALSO WE
HAVE A THE LARGE ARRAY OF
INVESTIGATORS, SOME ARE HARD
CORE ACADEMICS AND THEY KOANT
WANT TO START A COMPANY, THEY
JUST WANT THE TECHNOLOGY
DEVELOPED, WE HAVE SOME
ACADEMICS WHO WANT TO START A
BUSINESS BUT THEY DON'T KNOW
HOW, AND THEN WE HAVE
START-AUTOPSIES WHO UNDERSTAND
THE START UP BUT DON'T
UNDERSTAND THE NEXT STAGES OF
COMPANY DEVELOPMENT SO WE WORK
ACROSS THIS FULL GROUP OF TEAMS
TO HELP THEM MEET THEM WHERE
THEY'RE AT AND GET THEM TO WHERE
THEY WANT TO GO AS FAR AS THE
ENTREPRENEURIAL POSITION GOES.
AND THE PI IS A GROUP WE BRING
TO THE STABLE AND THE NEXT SLIDE
SHOWS WHAT WE -- THE
EXPECTATIONS AND THE OFFER OF
WHAT WE PROVIDE TO YOU.
SO EVEN AS EARLY AS POST PEER
REVIEW, WE WORK WITH THE
INVESTIGATORS TO RIGHT SIZE
MILESTONES, IF THERE'S SOMETHING
MISSING WE KNOW THE FDA WILL
WANT DOWN THE ROAD, WE BAKE
THOSE IN BEFORE WE FUND YOU.
AT THE KICKOFF MEETING WE
DEVELOP A PRODUCT DEVELOPMENT
PLAN WHICH I THINK IS PART OF
TOMORROW'S TALK, AND THEN, LONG
YOUR JOURNEY, WE MEET WITH YOU
QUARTERLY TO GO OVER ANY
TECHNICAL CHALLENGES, MILESTONE
REVIEW AND THEN YOU ALSO HAVE
ACCESS TO OUR TECHNICAL TEAM
ADHOC TO THEN IF YOU HAVE, YOU
KNOW, NEED TO SPEAK WITH OUR
MEDICINAL CHEMIST ABOUT YOUR
STRATEGY FOR STREAMING
MOLECULINGS OR IF YOU HAVE AN
ASSAY THAT'S NOT WORKING OUT WE
CAN TRY TO HELP TO IDENTIFY A
STRATEGY TO IDENTIFY AND GET
AROUND THE RISK THAT YOU'RE
HAVING.
NEXT SLIDE.
PLEASE.
AND WE ALSO ARE A STAND ALONE
PROGRAM, SO IF HAVE YOU SOME
DATA AND YOU WANT A GAP
ASSESSMENT TO SAY WHAT DO YOU
THINK I HAVE?
WHAT DO YOU THINK THE FDA WILL
NEED?
AS CARMEN MENTIONED WE CAN HELP
WITH THAT, AND WE CAN DO GAP
ASSESSMENT AND WE CAN HELP
PREPARE THE I90 AND HELP ENGAGE
WITH THE FDA AND IT'S A FULL
SPECTRUM OF RESOURCES, YOU NOW
HAVE TO HAVE CURRENT ACTIVE
AWARD, HOWEVER, IF YOU HAVE A
CATALYZE AWARD, REGULATORY
SERVICES COME AS A PART OF THE
PACKAGING, YOU DO NOT NEED TO
APPLY SEPARATELY FROM THAT.
AND AGAIN THIS IS TO GET YOU TO
THE IND AND HAND YOU OFF TO
OTHERS TO TAKE YOU THROUGH THE
CLINICAL TRIALS BECAUSE WE HAVE
ADDITIONAL FUNDING FOR THAT
STAGE OF DEVELOPMENT.
NEXT SLIDE.
GREAT.
SO UPPER LEFT HAND SIDE,
CATALYZE, THERE IS A SIGN UP
THERE WHERE YOU CAN GET OUR NEWS
LETTERS AND E-MAILS.
AGAIN, REACH OUT TO US IF YOU
HAVE AN IDEA OR WANT TO GET
FEEDBACK ON MORE DETAILS OF THE
PROGRAM.
WE ALSO HAVE A VERY ROBUST FAQ
PAGE AND WE ALSO SEND OUT
QUARTERLY NEWS LETTERS SO IF YOU
WANT TO GET THOSE, REACH OUT TO
US OR SIGN UP ON THE WEBSITE.
I THINK THAT'S MY LAST SLIDE.
>> AWESOME.
THANKS SO MUCH MIKE.
THAT WAS A FANTASTIC OVERVIEW,
SO MAYBE I COULD INVITE OUR
SPEAKERS FROM THE SESSION TO
COME BACK ON CAMERA, AND I THINK
YOU KNOW JUST TO KIND OF SUM UP
THAT SESSION, I KNOW WE COVERED
A LOT OF TERRITORY HERE FROM
REGULATORY ALL THE WAY UP TO
GENERATING FUNDING BUT I THINK
IT UNDERSCORES SOMETHING HOLLY
BROUGHT UP, THERE ARE A LOT OF
ONGOING CONCURRENT ACTIVITIES
THAT HAVE TO HAPPEN DURING THIS
PHASE IN ORDER TO BE SUCCESSFUL
AND THEN TRANSITION YOUR IDEA
INTO AN ASSET GOING FORWARD.
SO I THINK THAT'S REALLY WHAT
WE'RE TRYING TO CAPTURE IN THIS
GROUP.
SO MAYBE TO KIND OF KICKOFF ANY
-- FIRST OF ALL TO INVITE
EVERYBODY TO SEND THEIR
QUESTIONS TO THE Q&A LINK,IME
HAPPY TO SHARE THOSE WITH THE
SPEAKERS AND ASK THEM, BUT MAYBE
TO KIND OF KICK THINGS OFF, I
CAN ASK STEPHAN EXPE MIKE WHAT
ARE THE ATTRIBUTES YOU'VE SEEN
FOR THESE DIFFERENT SUBMISSIONS
THAT ARE LIKE ASSOCIATE WIDE
HIGH QUALITY SUBMISSIONS.
I MEAN, WHAT'S THAT PHENOTYPE OR
ATTRIBUTES THAT YOU'RE LOOKING
FOR THAT HAVE BEEN HISTORICALLY
SUCCESSFUL IN THIS SPACE?
>> YEAH, ABSOLUTELY.
SOPHISTICATED THERE ARE SEVERAL
AREAS OF MERITORIOUS
APPLICATIONS WE SEE THROUGH THE
SMALL BUSINESS PROGRAM.
ONE OF THE BIGGEST THINGS I SEE
THAT I WOULD SAY IS ASSOCIATED
WITH HIGH SCORING APPLICATIONS
IS TEAMS THAT DID THEIR HOME
WORK, ESPECIALLY EVEN IF IT'S AN
EARLY STAGE COMPANY, OR A NEW
SPIN OUT FROM AN ACADEMIC
INSTITUTION, WE WANT YOU TO BE
COMING IN WITH A GOOD IDEA ABOUT
WHAT YOUR UNMET MEDICAL NEED IS
AND HOW YOUR PROPOSED SOLUTION
WILL MEET IT AND ALSO WHAT'S
INNOVATIVE ABOUT YOUR PROPOSED
SOLUTION.
SO IF YOU HAVE SOMETHING THAT IS
SIMILAR TO OTHER DEVICES OR
DRUGS ON THE MARKET, WHAT MAKE
ITS BETTER?
IS IT SAFER?
EASIER TO USE?
LOWER COST TO MANUFACTURE?
THOSE ARE THINGS THAT IT'S
IMPORTANT TO EMPHASIZE.
YOU KNOW 1 OF THE OTHER THINGS I
SEE A LOT IS IF YOU ARE USED TO
WRITING RO-1S, THE THING TO KEEP
IN MIND WITH THESE PHASE 1 SMALL
BUSINESS GRANTS IS IT'S A MUCH
SMALLER GRANT, 1-2 YEARS, A FEW
THOUSAND THOUSAND DOLLARS, I
HAVE SEEN PIs GET TOO
AMBITIOUS AND GET DINGED ON
REVIEW ON APPROACH.
SO PHASE 1 IS JUST PROOF OF
CONCEPT, DON'T PUT TOO MUCH,
THERE ARE OTHER PHASES FOR THAT
AND FINALLY NOT HAVING THE
APPROPRIATE EXPERTISE.
SO IF YOU DON'T HAVE EXPERTISE
IN A PARTICULAR AREA THAT'S
NECESSARY FOR YOUR PROJECT, CALL
UP 1 OF YOUR COLLABORATORS, FIND
SOMEONE ELSE TO PROVIDE ADVISORY
SERVICES, SO IT'S OFTEN, THERE'S
A BIG FOCUS ON THE TEAM NOT JUST
THE CONTACT PI FOR THESE TYPES
OF APPLICATIONS.
>> IN ADDITION TO ALL THOSE
THINGS WHICH ARE TRUE FOR THE
CATALYZE PROGRAM, HAVING CLEAR
MEASURABLE MILESTONES FOR
CATARISE IS REALLY ESSENTIAL SO
THAT WE UNDERSTAND WHAT YOU
DETERMINED IS YOUR SUCCESS OR
FAILURE, AND THEN TIE TO THAT IS
GETTING OFTEN TIMES THE BEST
APPLICATIONS THAT I HAVE SPOKEN
TO US BEFORE HAND SO THEY
UNDERSTAND WHAT THE EXPECTATIONS
ARE EVEN BEFORE THE REVIEW
HAPPENS.
>> I THINK THAT'S GREAT FEEDBACK
THERE.
YOU KNOW, WHAT ARE SOME MAYBE
JUST KIND OF WORKING ALONG WITH
THAT, TOO, WHAT ARE THE TYPICAL
MISTAKES YOU SEE FOLKS MAKING
WITH THE SUBMISSION THAT THEY
SHOULD TRY AND AVOID.
>> I WILL JUST REITERATE, A LOT
OF TEAMS ARE OVERLY AMBITIOUS
ESPECIALLY IF WE ARE A 3 OR 2
YEAR PEER PROGRAM, AND SAY
YOU'RE GOING FROM SCREENING UP
TO YOUR LEAD MOLECULE ALL THE
WAY UP TO PREIND, OR IND, YOU
AGAIN, YOU GOT A LOT OF OVERLY
AMBITIOUS APPLICATIONS SO HAVING
REALISTIC TARGETS IN MIND IS
SOMETHING WE CAN GIVE YOU
FEEDBACK ON BEFORE HAND BUT IF
YOU COME IN KIND OF COLD, YOU
MAY ASSUME THAT THAT'S -- YOU
CAN ACTUALLY DO IT AND WE
ACTUALLY TERMINATE AWARDS EARLY
AND THAT'S 1 OF THE KIND OF
REOCCURRING PROBLEMS WITH THE 1
THAT HAVE DETERMINED IS THEY ARE
ABLE TO MEET THE MILESTONES
BECAUSE THEY SET THE BAR
UNREALISTICALLY.
NYEAH, I DEFINITELY AGREE WITH
WHAT MIKE SAID, YOU KNOW, A LOT
OF PEOPLE SEE BEING AMBITIOUS AS
A GOOD THING AND MANY CASES IT
IS, BUT NOT FOR THESE TYPES OF
PROJECTS.
THE REVIEWERS ARE LOOKING FOR A
TEAM THAT NOT ONLY KNOW WHAT IS
THEY WANT TO DO BUT ALSO IS
REALISTIC ABOUT THEIR
LIMITATIONS BOG BUDGETAR EXPE
TIME RELATED ALSO IN TERMS OF
THE BAND WIDTH OF THE TEAM.
SOME OF THE OTHER THINGS I SEE
ARE -- AND THESE ARE MORE
ADMINISTRATIVE MISTAKES BUT IT
HAPPENS A LOT.
SO FOR EXAMPLE, IF YOU'RE DOING
A HUMAN SUBJECT STUDY, IT'S
IMPORTANT WHETHER YOU KNOW
WHETHER IT'S FALLS UNDER THE NIH
DEFINITION OF A CLINICAL TRIAL
EMPLOY SO WE ALWAYS RECOMMEND
REACHING OUT TO I PROGRAM
OFFICER AT LEAST 1 MONTH IN
ADVANCE TO DETERMINE YOU A-KNOW
WHAT YOUR STUDY IS CLASSIFIED AS
AND THAT YOU'RE APPLYING TO
RIGHT NOTICE OF FUNDING
OPPORTUNITY.
FOR A SMALL BUSINESS GRANTS IN
PARTICULAR, THEY ARE THE OMNIBUS
GRANTS ARE SEPARATED INTO
CLINICAL TRIAL REQUIRED AND
CLINICAL TRIAL NOT ALLOWED SO
YOU DON'T WANT YOUR GRANT TO END
UP AS A MISCLASSIFIED CLINICAL
TRIAL.
ANOTHER THING IS IT'S REALLY
IMPORTANT TO READ THE INTRUKSS
SO THINGS LIKE THE PAGE LIMITS,
LOOKING OVER THE SF424, IT'S NOT
THE MOST INTERESTING DOCUMENT,
BUT TRUST ME WHEN I SAY THIS IT
IS 1 YOU WANT TO KEEP ON
MANDATORY BECAUSE A LOT OF YOUR
MOST COMMON ANSWERS WILL BE IN
THAT DOCUMENT.
>> GREAT.
I THINK WE WILL JUMP AROUND A
BIT.
THE NEXT QUESTION IS FOR KEVIN
THAT CAME FROM ONLINE HERE.
HOW DOES 1 MAKE A DECISION
BETWEEN THE DPI, THE DRUG
PRODUCT, I ASSUME FORMULATION
AND AEROSOL OR BOTH?
AS IT'S COSTLY TO DO DIFFERENT
FORMULATIONS.
WHAT DATA WOULD HELP TO MAKE
THOSE DECISIONS?
>> WOW, WE COULD SPEND THE REST
OF THE DAY ON THIS TOPIC
ACTUALLY.
[LAUGHTER]
I MEAN, IT'S A VERY REAL
QUESTION AND THE FORMULATION
WORK IS SO HARD, IT IS SO
EXPENSIVE, IT CAN BE SO TIME
CONSUMING AND I DON'T THINK -- I
DON'T THINK I HAVE A GOOD ANSWER
THERE OTHER THAN DON'T LET THE
[INDISCERNIBLE] GOOD THAT VERY
COMMONLY FORMULATION WORK IS
NECESSARILY ITERATIVE.
APPROACHES THAT I'VE WORKED SORT
OF WITH MYSELF AND CLIENTS ON IS
INITIALLY DON'T REINVENT THE
WHEEL.
IF THERE IS GOOD PRECEDENT OUT
THERE OF, OH, GREAT, HERE'S
SOMEBODY THAT HAS USED
X-FORMULATION BUFFER WITH A
PRODUCT THAT LOOKS SIMILAR TO
MINE, THAT WOULD BE A REALLY
GOOD PLACE TO START AND IF
YOU'RE GETTING THE PROPERTIES
THAT YOU NEEDED, YOU ARE GETTING
REASONABLE REASONABLE PARTICLE
DISTRIBUTION, IF YOU'RE GETTING
REASONABLE PRODUCT IN THE RIGHT
RANGE, GREAT.
BUT YOU NEED TO BE PREPARED FOR
-- YOU TALKED ABOUT CMC, EARLIER
TODAY, IF YOU'RE FOLKS ARE
LOOKING AT STABILITY, IF IT
TURNS OUT THAT STABILITY IS NOT
GREAT IN YOUR FORMULATION BUFFER
THAT MIGHT BE A SITUATION WHERE
YOU NEED TO GO BACK AND LOOK AT
IT AND UNFORTUNATELY IF THAT'S
WHAT YOU NEED DO, IT WILL
REQUIRE RETREADING SOME OF THE
SAME GROUND , SO NECESSARILY
PRODUCT DEVELOPMENT IS NOT
LINEAR IT'S ITERATIVE AND
UNFORTUNATELY THAT'S THE REALITY
WE WORK IN.
AEROSOL PRODUCTS ARE COMPLICATED
AND EXPENSIVE AND THAT'S THE
REALITY BUT IT GIVES YOU THE
ABILITY TO GO AFTER DISEASES
THAT YOU CAN'T WITH OTHER FORMS
OF RESPIRAIGZ SO I'M SORRY BUT
IT'S THE ANSWER.
>> IT'S A GOOD 1.
SO OUR NEXT QUESTION IS FOR
CARMELLA.
YOU CAN IMAGINE A LOT OF FOLKS
ON THIS CALL MAY BE INTERESTED
WITH THEIR FIRST REGULATORY IRPT
ACTION BETWEEN AN INTERACT
MEETING AND THEY APPLY AND A LOT
OF FOLKS GET SHOT DOWN TO HAVE
THAT MEETING SO MAYBE YOU COULD
TALK AROUND WHY FOLKS GET SHOT
DOWN FOR THAT MEETING AND THEN
NOT TO DESPAIR IN HOW THEY CAN
KIND OF SHIFT AND WHAT THEIR
NEXT STEPS ARE GOING FORWARD.
>> WELL THE INTERACT MEETING IS
REALLY -- IT'S GOT STARTED IN
SELLING GENE THERAPY.
AND REALLY LOOKING AT NEW AND
VERY INNOVATIVE TECHNOLOGIES,
TECHNOLOGIES WHERE THERE WEREN'T
GOOD GUIDANCE DOCUMENTS
AVAILABLE FOR REVIEW AND SO,
IT'S REALLY TRANSFERRED OVER
INTO ANYTHING UNDER CDER OR CBER
NOW, BUT THAT'S WHAT YOU NEED TO
CONSIDER IS THAT USUALLY IF IT'S
REALLY NEW, REALLY INMODEL
CITIZENIVATIVE, REALLY, THERE'S
NO SPECIFICKIFIEDANCE DOCUMS OUT
THERE, THEN YOU MIGHT GET SHUT
DOWN.
THE OTHER -- I MEAN, OR YOU
WOULD GET A MEETING.
THE OTHER THINGS THAT ARE OFTEN
TIMES SELECTED IF YOU HAVE SAY
AN ISSUE WITH YOUR ANIMAL MODEL
OR YOUR END POINT, THEN USUALLY,
IF THERE'S NOT A GOOD ANIMAL
MODEL AND YOU'RE COMING UP WITH
A NEW ANIMAL MODEL OR A NEW
STRATEGY, THEN USUALLY THOSE ARE
THE KINDS OF THINGS THAT GET
SELECTED FOR AN INTERACT
MEETING.
HOW'S THAT?
>> THAT IS I THINK A GREAT PLACE
TO START.
THANKS CARMELLA.
SO GOING BACK TO SOME OF THE
QUESTIONS ONLINE, I THINK THE
NEXT QUESTION'S FOR MIKE, A
QUESTION HERE IS FOR CATALYZE,
DOES NHLBI REQUIRE THAT THE
START-UP HAS ALREADY LICENSED
THE IP?
USUALLY THIS IS OWNED BY THE
UNIVERSITY AND OURS REQUIRES THE
START-UP COMPANY TO BE QUITE FAR
ALONG BEFORE THEY WILL LICENSE
IT TO THEM?
>> SO, THERE'S NO REQUIREMENT TO
HAVE IP AT THE TIME OF
APPLICATION, WHAT WE'RE LOOKING
FOR IS INDICATION IN THAT IP
STRATEGY THAT MAYBE YOU SPOKEN
TO THE TECH TRANSFER OFFICE OR
HAVE YOU SOME LINE OF
COMMUNICATION SO THAT THEY'RE
AWARE THAT YOU ACTUALLY WANT
THEIR TECHNOLOGY AND THAT'S WHAT
WE'RE REALLY LOOKING FOR AND
THEN ONCE YOU'RE IN THE PROGRAM,
WE WILL WORK WITH YOU AND INSURE
THAT THE RIGHT PEOPLE ARE AT THE
MEETINGS, WHEN WE KIND OF
DISCUSS THE TECHNOLOGY BEING
DEVELOPED.
THE OTHER PART I SHOULD NOTE IS
THAT IF YOU ARE DOING ANY KIND
OF RESEARCH ON A -- SOMETHING
THAT'S IP PROTECTED LIKE A
COMPOUND FOR EVEN AN OFF LABEL
USE, WE DO EXPECT YOU TO HAVE A
LETTER OF SUPPORT FROM THE IP
HOLDER OF THAT MOLECULE OR
COMPOUND AT THE TIME OF
APPLICATION.
>> THANKS MIKE.
SO, I THINK THE LAST QUESTION
WE'RE GOING TO TAKE FOR THE SAKE
OF TIME WILL PROBABLY BE
SOMETHING KEVIN AND I MIGHT
SPLIT BUT I'LL LET HIM TAKE THIS
1 FIRST.
THE QUESTION IS CONCERNING A
PEPTIDE THAT WILL BE
ADMINISTERED INTRA FECALLY,
WOULD THE PANELISTS SUGGIEST ANY
INVITRO OR IN VIVO IMMUNOLOGICAL
PRECLINICAL TESTING TO EVALUATE
SAFETY?
YOU WANT TO TAKE THAT 1 KEVIN?
>> THAT WAS A VERY DIFFICULT
QUESTION TO GET INTO WITHOUT
KNOWING THE SPECIFIC INDICATION
THAT -- SO THAT'S REALLY
IMPORTANT.
I MEAN REALLY IT AMOUNTS TO A
RISK BENEFIT ASSESSMENT.
SO VERY CALMLY, SO INTRA FECAL
IS AN INTERESTING 1, I CERTAINLY
HAVE SEEN THE FDA BE ACCEPTING
OF IND ENABLING PACKAGES THAT
DID NOT NECESSARILY REQUIRE
LARGE ANIMAL MODELS IN CONTRAST,
IF IT'S AN INJECTION COMMONLY,
YOU WILL NEED A LARGE ANIMAL
MODEL, SO AND WHAT IS THE
MECHANISM OF ACTION, HOW DOES IT
INTERACT WITH, IS THERE
SUFFICIENT HOMOLOGY THAT
INTERACTS WITH THE SPECIES
APPROPRIATELY, THERE ARE A LOT
OF DIFFERENT CONSIDERATIONS
AROUND THIS.
NHEY, KEVIN, I HAVE TO CUT YOU
OFF THEIR 1 SECOND, I MISSPOKE,
AND KEVIN, THANK YOU.
INTRA TRACHEALLY.
I'M SORRY.
>> OH, OKAY.
>> IT MAKES MORE SENSE FOR OUR
DISCUSSION.
>> THIS 1'S AN OUTLIAISONNER, SO
AEROSOL VERSUS INTRA TRACHEAL
INSTALLATION.
>> YEAH.
>> SO THIS IS AN INTERESTING
QUESTION, SO INTRA TRACHEAL
INSTALLATION HAS BEEN USED VERY
SUCCESSFULLY FOR IN SMALL ANIMAL
EFFICACY MODELS WHERE YOU'RE
LOOKING TO SHOW BIOLOGICAL
ACTIVITY OF YOUR PRODUCT, WHICH
CAN BE REALLY USEFUL PROOF OF
PRINCIPLE, GETTING FROM THE --
EXTRAPOLATING FROM THAT TO AN
AEROSOLIZED DOSE CAN BE QUITE
CHALLENGING, SO, I THINK IT
THINK IT WOULD BE GREAT, VERY
USEFUL TO DEMON TRAIT EFFICACY.
THERE WON'T NECESSARILY BE A BIG
TRANSITION TO MOVE FROM THAT TO
DEVELOPMENT OF YOUR AEROSOL AND
COLLECTING APPROPRIATE SAFETY
DATA IN AN HAN MALFOR WHICH YOU
CAN DELIVER AEROSOL.
SO INTRA TRACHEA INSTALLATION,
IN AND OF ITSELF WILL BE
DIFFICULT FOR SINGULAR IND
ENABLING, IT WOULD BE IND
SUPPORTED AND WOULD NEED TO BE
PAIRED WITH SOME OTHER STUDY
SAYS ASSUMING AEROSOL WILL BE
INTENDED CLINICAL ROUTE.
>> CARMELA DO YOU HAVE ANYTHING
TO ADD TO THAT FROM YOUR
PERSPECTIVE?
>> RIGHT, BASICALLY IT'S WHAT WE
TRY TO TELL IS TO START OUT
WITH, YOU KNOW THE ROUTE THAT
YOU'RE GOING TO GO WITH
APPROXIMATE YOU -- IF YOU KNOT
THAT IS.
AND WHAT I WANT TO BRING UP IN
THE PRODUCT SYSTEM THAT REMEMBER
BY PHASE 2, YOU HAVE TO HAVE
YOUR DEVICE DESIGN ESTABLISHED
AND IF YOU ARE GOING TO HAVE A
NEBUEALIZED PRODUCT, YOU HAVE TO
INCLUDE THE SPECIFIC NEBULIZER
IN YOUR LABEL.
>> GREAT.
THANK YOU VERY MUCH.
FOLKS, I REALLY APPRECIATE THE
PANEL'S FEEDBACK HERE.
I'M SORRY, COULD PROBABLY KEEP
GOING BUT TO STAY ON SCHEDULE, I
THINK WE WILL CALL IT THERE AND
MAYBE I CAN TURN IT BACK OVER
TOMORROW FOR OUR TRANSITION TO
THE NEXT PHASE.
THANK YOU.
NTHANK YOU ALL.
SO WE HAVE ABOUT 20 MINUTES LEFT
IN THE AGENDA FOR A NETWORKING
BREAK.
AND SO THIS IS AN OPPORTUNITY
FOR INDIVIDUALS ONLINE TO FEEL
FREE TO COME ON CAMERA AND CHAT
WITH ANY OF THE PANELISTS, WHO
SPOKE TODAY OR ANY OF THE
INDIVIDUALS IF THE MEETING AND
THEN WE WILL BEGIN SESSION 3,
WHICH IS DEFINING THE TARGET
PROFILE AT PROMPTLY 3:00 P.M. EASTERN TIME.
DEFINING THE PRODUCT
PROFILE AND DR. ZIADY AND
DR. WEST WILL BE YOUR MODERATORS
AND I WILL TURN IT OVER TO THEM.
>> HI, EVERYBODY, JUST A BIT
ABOUT MYSELF AND THEN JAMES CAN
GO.
I'M A PROPESESSOR AT SEN
CINCINNATI
CHILDREN'S MEDICAL CENTER AND
HOSPITAL, I'M JUST A Ph.D., I
HAVE TAKEN QUITE A FEW BUSINESS
CLASSES AND I WAS ASKED TO DO
THIS BECAUSE OF MY BACKGROUND IN
SOME COMMERCIALIZATION
DEVELOPMENT AND I'VE BEEN
INVENTOR ON A NUMBER OF PATENTS
GRANTED AND SOME PROVISIONAL
PATENTS THAT ARE PENTINE REGIMEN
NOTHING TECHNOLOGIES THAT WE'VE
WORKED WITH AT CHILDREN'S, EMORY
AND CASE WESTERN SO WE'LL CHAT
ABOUT THAT IN MY LITTLE 10
MINUTE SPEECH.
>> THANK YOU AND I'M JAIPS WEST,
PROFESSOR AT VANDERBILT.
I'M FAIRLY SURE I WAS ASKED
BECAUSE I HAVE GOTTEN A FAIR
NUMBER OF DRUGS THROUGH FROM THE
CLINIC TO THE BENCH AND HAD A
LOT OF INDUSTRY COLLABORATIONS
SO HAVE A FAIR AMOUNT OF
EXPERIENCE IN THIS SPACE AS
WELL.
>> I THINK THE SESSION WAS PUT
TOGETHER PRETTY NICELY.
IT WILL EXPOSE THE VIEWERS TO A
MIX OF ENTREPRENEURS THAT HAVE
ACTUALLY BEEN IN THE SMALL
BUSINESS PLACE AND YOU KNOW
BASICALLY WORKED ON TAKING THEIR
DRUGS TO MARKET AND CREATING
SMALL COMPANIES AND SORT OF
BRINGING THAT TO MARKET AND THEN
WE'LL ALSO HEAR FROM A COUPLE OF
SPEAKERS ON FUNDING AND SUPPORT
AND VENTURE CAPITAL SUPPORT FOR
THIS WORK, SO I THINK OUR FIRST
TALK WILL BE BY DR. HOLTZMAN
WHO'S FOUNDER AND PRESIDENT AT
NUPEAK AND THEN WE WILL HEAR
FROM ENRIQUE SHIAO, FROM THE
HEAD OF SEARCH AND EVALUATION
AND THEN LUCY LIU AT LONG WOOD
FUND AND THEN WE WILL WRAP UP
WITH STEPHEN BENOIT FROM MDI
THERAPEUTICS.
>> OKAY, I'M ON, I GUESS.
FIRST LET ME THANK THE
ORGANIZERS AND THE INTRODUCERS
FOR THE OPPORTUNITY.
IT'S BEEN A TERRIFIC MEETING FOR
ME SO FAR AND I APPRECIATE BEING
PART OF IT.
MY TALK'S GOING TO BE A BIT
DIFFERENT I THINK THAN SOME OF
THE 1S YOU'VE HEARD PREVIOUSLY
AND I WILL TRY TO CONVEY THE
VIEW I HAVE FROM, YOU KNOW OUR
YOWRNY IF YOU WILL FROM INITIAL
DISCOVERY TO WHERE WE'RE AT NOW
WHICH IS ESSENTIALLY PREIND
STAGE.
SO NEXT SLIDE.
FOR SOMETHING A LITTLE
DIFFERENT, FIRST I JUST WANT TO
INTRODUCE WHO I AM AND WHERE I'M
AT AND THEN I WILL SPEND THE
MAIORITY OF MY TEAM IN A MORE
GENERAL MODE TO TRY AND GIVE YOU
THINGS THAT MIGHT BE HELPFUL.
SO THE FIRST POINT, I WANT TO
MAKE IS THIS IS THE WAY I DID IT
AND THOSE OF YOU IN THIS
AUDIENCE WHO HAVE A BIT MORE
YEARS ON THEM WILL REMEMBER
FRANK SINAT RA, THE ORIGINAL
HEAD OF THE BOARD WHO HAD THE
FAMOUS SONG, I DID IT MY WAY AND
I DID, BUT I WANT TO MAKE MY
POINT THAT IN SPITE OF ALL THE
SUGGESTIONS AND RECOMMENDATIONS
AND TEMPLATES THAT YOU WILL SEE,
YOU WILL HAVE TO DO IT YOUR WAY.
EACH PROJECT IS DIFFERENT AND A
LOT OF THE PERSPECTIVE HERE WILL
BE BASED ON MY EXPERIENCE BUT
YOU WILL HAVE TO FIND SOMETHING
THAT'S MORE TAILORED TO YOUR
PROJECT, SO IF YOU DON'T
REMEMBER ANYTHING ELSE I SAID,
REMEMBER THAT ADVICE IS GREAT,
BUT IT'S REALLY UP TO YOU TO BE
THE BEST PERSON TO FIGURE IT
OUT.
NEXT SLIDE.
AND TO DO THAT, YOU WILL NEED A
TEAM OF PEOPLE AND FIRST TO
THANK THESE GUYS AND TO SHOW YOU
THAT THAT EXISTS IN MY CASE.
I'VE TAKEN A HYBRID APPROACH, SO
ON THE LEFT SIDE YOU WILL SEE
THE TEAM AT WASH-U AND ST. LOUIS
IN THE RIGHT SIDE YOU WILL SEE
THE TEAM AT NUPEAK THERAPEUTICS
THAT I STARTED IN 2012 EMPLOY
YOU CAN SEE THAT BOTH HAVE GROWN
INTO A VERY EXTENSIVE CAST TO
COVER WHAT I CALL THE FULL
SPECTRUM DRUG DISCOVERY AND
DEVELOPMENT TO THE PROGRAM.
SO THE LEFT SIDE OF THE SCREEN
IS DISCOVERY EMECHANISM AND
SCIENCE AND THE RIGHT SIDE OF
THE TEAM IS RESPONSIBLE FOR
BRINGING IT INTO THE
COMMERCIALIZATION PROCESS AND
I'M FAMOUSLY KNOWN FOR NOT
KNOWING ENOUGH ABOUT EITHER SO
BOTH SIDES ARE ABLE TO CRITICIZE
ME ON A PRETTY SIGNIFICANT BASIS
BUT IN GENERAL, THIS KIND OF
APPROACH HAS WORKED WELL FOR ME.
I DON'T RECOMMEND IT TO
EVERYONE, BUT IT DOES ALLOW YOU
TO COVER THE FULL GAMUT OF THE
APPROACHES WHICH HAS BEEN
HELPFUL.
NEXT SLIDE.
NEXT SLIDE, PLEASE.
SO JUST 1 WORD ABOUT WHAT I'M
DOING AND THEN I WILL GO INTO A
MORE GENERAL MODE.
SO THIS CARTOON SYMBOLIZES MY
LIFE OVER THE LAST DECADE, AND
THE APPROACH THAT WE'VE TAKEN TO
FIGURE OUT A NEW DRUG FOR
PREDOMINANTLY COMMON LUNG
DISEASES AS AMONG COPD AND IT
JUST DEPICTS THE NOTION THAT I
WILL MAKE TO YOU SEVERAL TIMES
THAT WE'VE GONE AFTER NEW
CELLULAR AND MOLECULAR TRARGETS
IN EPITHELIAL CELLS AND STRESS
KINASES AND WE STARTED OFF A
SCREAM FROM THE LEFT TO RIGHT
WHERE THERE'S INITIAL INJURY AND
THEN STEM CELLS ARE REPROGRAMMED
TO CAUSE GROWTH, EXCESS,
ACTIVATION, INFLAMMATION, MUCUS
PRODUCTION WHICH ARE ALL
HALLMARKS OF CHRONIC LUNG DEC
AND WE DEVELOPED A SPECIFIC
KINASE INHIBITOR TO TRY TO DOWN
REGULATE THAT PROCESS AND
THEREBY FIX THE DEC.
SO THAT'S THE PERSPECTIVE I'M
COMING FROM, SMALL MOLECULE DRUG
DEVELOPER WORLD BUT I WANT TO
TAKE WHAT I'VE LEARNED THERE,
NOT TELL YOU ABOUT ALL THE
DETAILS OF THIS, COMPARED TO
SOME OF THE SPEAKERS, BUT TRY TO
TAKE WHAT I'VE LEARNED THERE AND
PROVIDE THE PEARLS FROM THAT IN
A MORE GENERAL CONTEXT.
NEXT SLIDE.
SO TO DO THAT, I WILL RUN
THROUGH PRETTY QUICKLY 5-POINTS
LISTED HERE, AS WHAT I CALL THE
BIG PICTURE MILESTONES THAT GOT
US AND HOPEFULLY CAN GET YOU
FROM THE BEGINNING TO THE END OF
THIS PATHWAY.
SO FIRST WE'LL DISCOVER, YOU
KNOW THE NEW TARGET, SMALL
MOLECULE, THEN THE DRUG, THEN
THE REGULATORY PROCESS, THEN THE
TRIALS AND THEN THE PAYMENT
STORY.
SO INCOME SLIDE.
SO WE WILL START WITH FIRST 1
WHICH IS AS A MENTIONED TO YOU
WE DID FOR OURSELVES IN THE WAY
OF STEM CELLS AND KINASES AND
NOW TRY TO TAKE YOU A LITTLE BIT
THROUGH SOME OF THE PRIORITIES
AND HELPFUL GUIDES, HOPEFULLY IN
DOING THAT FOR YOU ALL.
NEXT SLIDE.
THERE WE GO.
SO THE FIRST THING TO SAY IN
GETTING A NEW TARGET IS THAT IT
SHOULD BE NEW.
SO I WANT TO EMPHASIZE THAT NOT
TO DO WHAT'S BEEN DONE BEFORE
BUT TO DO SOMETHING ENTIRELY
DIFFERENT AND NOVEL.
THIS WILL BE PROJECT SPECIFIC,
AS I MENTIONED WE'RE ON TO STEM
CELLS AND KINASES BUT IT'S GOING
TO BE DIFFERENT FOR YOU.
IN SPITE OF THAT DIFFERENCE
THERE ARE DIFFERENT TIPS IN
GENERAL, I FELT TO LOOK AT WHAT
WE'VE DONE.
FIRST AS I'M UNDERLINING HERE,
AIM FOR NOVELTY, PARTICULARLY ON
THE SCIENCE SIDE BUT ALSO ON THE
TRANSLATION OF THAT INTO THE
COMMERCIAL END.
SO YOU WANT NEW SCIENCE AND A
NEW INDICATION AS YOUR BEST
STRATEGY, I THINK TO BE
INNOVATIVE AND APPEALING AND TO
MAKE IT TO THE GOALPOST.
AND 2 OTHER POINTS I WANT TO
EMPHASIZE HERE, 1 EARLY ON TO
VALIDATE THESE TARGETS IN
PRECLINICAL MODELS THAT ARE HIGH
FIDELITY AND THAT MEANS BEING
ABLE TO TRACK THE TARGETS,
APPROPRIATELY AND HOPEFULLY, IN
MOST CASES KNOCK OUT THE TARGET
BOTH EXVIVO AND IN VIVO, TO BE
SURE THAT YOU HAVE THE RIGHT
TARGET.
AND I CAN TELL YOU, I KNOW 90
TIMES OUT OF A HUNDRED, THE
PROJECTS I FEEL HAVE NOT DONE
THAT, SO EARLY ON, YOU WANT THAT
INFORMATION AND THEN SECONDLY,
ALSO RARELY DONE, TRY TO
VALIDATE IT ALSO IN THE HUMAN
MODEL.
BOTH IN CELLULAR MOLECULAR
MODELS AND ALSO IN CLINICAL
SAMPLES THAT ARE RELEVANT TO YOU
WHAT YOU'RE TRYING TO DO.
AGAIN, YOU WANT TO TRACK THAT
CAREFULLY, SO YOU KNOW IF YOUR
TARGET IS REPRESENTATIVE AND
FUNCTIONAL AND ALSO WHEN
POSSIBLE, TRY TO KNOCK IT OUT AT
LEAST IN A CELL MODEL TO MAKE
SURE IT'S VALID.
NEXT SLIDE.
THERE WE GO.
SO STEP 2, ONCE YOU HAVE A CELL
OF TARGET AND INTEREST, THEN OF
COURSE YOU HAVE TO DISCOVER AND
OPTIMIZE A DRUG CANDIDATE TO HIT
THAT TARGET.
NEXT SLIDE.
SO 2 WORDS OF ADVICE HERE, FIRST
IN THE PRECLINICAL SPACE AND
THEN IN THE CLENICAL SPACE.
IN THE PRECLINICAL SPACE AFTER
YOU HAVE YOUR TARGET, IN THE
CASE OF SMALL MOLECULES THAT
MEANS STRUCTURE BASED DRUG
DESIGN NOWADAYS AIDED BY AI
METHODS, EDITORIALLY SPEAKING AI
METHODS ARE NOT SUFFICIENT IN
THEMSELVES, DON'T BELIEVE THAT
ADVERTISING, BUT YOU KNOW A LINK
TO CONVENTIONAL TECHNIQUES CAN
BE VERY VALUABLE.
THE END POINTS THERE THAT I
WANTED TO EMPHASIZE, VERY
POTENT, VERY SAFE, VERY
SELECTIVE, AND HOPEFULLY
DEVELOPED IN A HIGH FIDELITY
CELLULAR MODEL SYSTEM.
THOSE PIECES OF INFORMATION WILL
BE VERY VALUABLE TO YOU AS YOU
GO THROUGH THE NEXT STEPS I WILL
SHOW YOU.
ONCE YOU'VE GOTTEN THROUGH THAT,
YOU NEED TO MAKE IT PROPERLY,
FORMULATE IT PROPERLY, AGAIN
THINKING ABOUT SAFETY AND
SPECIFICITY AND SELECTIVITY AS
KEY END POINTS TO SUCCESS.
THIRDLY, IN THIS PROCESS, TALKED
A LITTLE BIT ABOUT THIS BUT YOU
WANT A MECHANISM OF ACTION, IT'S
UNABLE HOW MANY DRUG CANS GO
FORWARD WITH NO KNOWLEDGE OF
MECHANISM.
YOU WANT INSTEAD TO HAVE A
MECHANISM THAT SHOWS POTENCY,
AGAIN, SAFETY, AND AGAIN,
SCIENTIFIC NOVELTY.
THAT WILL ALL SERVICE YOU VERY
WELL AS YOU ANY THROUGH THIS
PROCESS.
AND THEN LASTLY THE END POINT OF
THIS IS PROOF OF CONCEPT AND
PRECLINICAL AND CLENICAL
GUIDANCE AND ONCE AGAIN, I WOULD
EMPHASIZE, POTENCY, SAFETY,
VALIDATE YOUR TARGET, MAKE SURE
THAT IT'S HIT, ENGAGED AND
BLOCKED AND ALL THAT IS BEST
DONE IN A HIGH FIDELITY
PRECLINICAL ANIMAL MODEL.
THERE AGAIN A LOT OF MILES USED
THAT ARE NOT WHAT I WOULD CALL
HIGH FIDELITY TO THE CLINICAL
CONDITION.
NEXT SLIDE.
SO THAT'S THE CLINICAL END, THE
PRECLINICAL PART TO THIS STORY,
VERY SIMILAR TO WHAT I SHUOF THE
SHOWED YOU.
AGAIN, DATA PROJECT SPECIFIC,
JUST AS OTHER DATA BUT AGAIN,
GENERAL GUIDE LINES THAT COULD
BE HELPFUL EMPLOY ONCE IMEAN, I
EMPHASIZE 3 THINGS, FIRST AGAIN
AIM FOR NOVELTY IN PARTICULAR
RELEVANCE, YOU KNOW THE
INDICATION THAT YOU'RE WORKING
TOWARDS, I THINK THE NOVEL
ASPECT IS EXTREMELY USEFUL FOR
MANY REASONS, AS WE'LL ROLL OUT
HERE IN THE NEXT FEW SLIDES.
AGAIN, I THINK IT'S IMPORTANT TO
VALIDATE WHAT YOU FIND IN
CLINICAL SAMPLES.
MAKE SURE THE TARGET'S THERE,
IT'S UPREGULATED, POTENTIALLY IN
YOUR DISEASE AND ALSO, I REALLY
WANT TO EMPHASIZE IS THAT WHEN
YOU'RE DOING THIS, CONSIDER THIS
AS EXTENDING IT INTO THE
DEVELOPMENT OF BIOMARKERS AND
YOU'LL NEED THOSE BIOMARKERS FOR
PATIENT SELECTION AND MONITORING
FOR PROOF OF CONCEPT AND EARLY
CLINICAL PHASE TRIALS, AND TO
DEMONSTRATE ONCE AGAIN THAT YOU
HAVE TARGET ENGAGEMENT AND
BLOCKADE OR PROMOTION, OR
WHATEVER THE END POINT HAPPENED
TO BE BUT THOSE BIOMARKERS AS I
WILL SHOW YOU IN JUST A SECOND,
CAN BE VERY USEFUL IN DESIGNING
THE CLINICAL TRIAL AND FOR
PROVING THAT YOU HAVE SOMETHING
USEFUL.
NEXT SLIDE.
SO AFTER DISCOVERING THE TARGET
AND DISCOVERING THE DRUG TO
BLOCK IT, YOU GET THE
OPPORTUNITY OF RUNNING THROUGH
THE MANUFACTURING AND SAFETY
WHAT I CALL GAUNTLET TO IND
APPROVAL AND PART OF THAT IND
PROCESS WE'LL DISCUSS IN JUST A
SECOND IS DESIGNING AND THEN
PERFORMING YOUR CLINICAL TRIALS.
NEXT SLIDE.
SO HERE I JUST TRIED TO DISTILL
DOWN AS I CHECK LIST.
IT WAS DIFFICULT FOR ME TO GET
THIS LIST IN ORDER OVER THE
YEARS AND NOW I WOULD LIKE TO
SHARE IT WITH THE WORLD IN TERMS
OF DOING THE MANUFACTURING AND
GETTING THE SAFETY DONE.
I KNOW SOME OF THIS HAS BEEN
TALKED ABOUT ALREADY IN TERMS OF
THE IND PROCESS, BUT IN SIMPLE
TERMS, CMC FIRST OF ALL, YOU'RE
GOING TO WAIT ON MANUFACTURE,
YOU'LL GOING TO WAIT ON GMP AND
JOHN GMP, SO YOU CAN DO GLP AND
NONGLP TRIALS, BE CAREFUL HOW
YOU DO THIS AND CHECK WITH
EXPERTS BEFORE, BECAUSE IT'S A
TRICKY BUSINESS COMING FROM 1
ACADEMIC BACKGROUND AND THEN YOU
WANT TO GO ON AND DO THE
TOXICOLOGY, BOTH INVITRO AND IN
VIVO, THIS HASN'T BEEN SAID
BEFORE, THE INVITRO IS USEFUL
RELATIVELY CHEAP AND FOOF THE
AND INFORMATIVE AND THEN YOU
MOVE TO TOX IN VIVO USING ANIMAL
MODEL, USUALLY 2 SPECIES, SO
MTD-DRF, IN 2 SPECS, RAT AND DOG
IS THE GO TO, AND THEN YOU MOVE
TO GLP TO TOCKSITY TO WRAP UP
WHAT THE FDA WILL WANT.
I JUST WANT TO EMPHASIZE HERE --
OOPS CAN YOU GO BACK.
GO -- OKAY, WHERE ARE WE GOING.
SO JUST TO EMPHASIZE HERE, THE
PK ANALYSIS I BELIEVE IS VERY
USEFUL UNDER THESE CONDITIONS,
YOU KNOW TO DETERMINE WHAT KIND
OF DOZING, WHEN YOU DOSE, HOW
YOU DOSE, HOW MUCH YOU DOSE, AND
A LOT OF TIMES PEOPLE JUMP INTO
TOXICITY WITHOUT HAVING THE FULL
KNOWLEDGE OF THAT DATA IN A FULL
RAINCHL OF SPECIES IN OUR CASE
AND I BELIEVE IN OTHERS THAT
WILL BE VERY USEFUL TO YOU AS
YOU MARCH THROUGH DESIGN HOW TO
SET UP THOSE STUDIES TO MAKE
SURE YOU DON'T NEED TO RUN THEM
2 AND 3 TIMES.
AND THE OTHER THING I WANT TO
EMPHASIZE ALTHOUGH I THINK THIS
WAS TALKED ABOUT SIGNIFICANTLY
IN THE LAST SESSION IS THE RULES
DIFFER, THIS LIST CHANGES FOR
INHALED VERSUS SYSTEMIC DELIVERY
AND WE WON'T HAVE THE SAME TO
DISCUSS THAT EXTENSIVELY, BUT
THE INHALED IS A TREMENDOUS
ADVANTAGE IF YOU CAN TAKE IT BUT
IT DOES HAVE A DIFFERENT SET OF
PROBLEMS AND ISSUES COMPARED TO
SYSTEMIC DELIVERY.
NEXT SLIDE.
AND THEN, YOU WANT TO TAKE ALL
OF THAT INFORMATION ON YOUR
PHARMACOLOGY MANUFACTURING AND
INTOXICOLOGY AND RUN THROUGH IN
TERMS OF THE SPECTRUM WE'RE
LOOKING AT TODAY WHAT I WOULD
CONSIDER PHASE 1 A AND B AND 2 A
CLINICAL TRIALS.
NEXT SLIDE.
SO SOME OF THIS YOU ALREADY
HEARD BUT PHASE 1 A AND B ARE
ASCENDING, MULTILE ASCENDING
DOSE TRIALS AND PHASE 2 IS THE
SAIOF THE AND EFFICACY TRIAL.
I WANT TO EMPHASIZE COUPLE
THINGS HERE WHERE I THINK A LOT
OF PROJECT VS RUN INTO TROUBLE.
SO FIRST IN THIS PHASE 1 AND
PHASE B FREQUENTLY DESIGNED FOR
SAFETY, BUT IT'S AN OPPORTUNITY
EARLY ON TO INCLUDE A PATIENT
ARM FOR AN EARLY READ OUT BOTH A
AND B.
AND THAT'S TERRIFICALLY VALUABLE
BECAUSE IT CAN GIVE YOU FIRST OF
ALL SOME EVIDENCE THAT YOU ARE
HITTING YOUR TARGET, YOUR
TARGET'S ENGAGED AND BLOCKED AND
ALSO IF YOU'RE REALLY LUCKY AND
YOU'VE DONE YOUR BIOMARKERS
PROPERLY, IT MIGHT GIVE YOU
EARLY EVIDENT THAT YOUR APPROACH
IS WORKING.
SAME THING IN 2A, BE CAREFUL
ABOUT TRYING TO INCLUDE SOME
EVIDENCE OF VALIDATION FOR
THERAPEUTIC EFFECTIVENESS OR AT
LEAST BIOMARKER ENGAGEMENT.
SO THE PS HERE IS BE THOUGHTFUL
ON PATIENT SELECTION.
THINK ABOUT VALIDATION BASED ON
THE SCIENCE YOU HAVE AND NOT ON
CONVENTIONAL, TRADITIONAL MODELS
THAT HAVE BEEN TRIED OVER AND
OVER AND HAVE GENERALLY FAILED
IN THE SAME DEC.
-- DISEASE.
NEXT SLIDE.
LASTLY, BUT NOT LEASTLY OF
COURSE, IS PAIN FOR ALL THESE
THING -- PAYING FOR ALL THESE
THINGS, SINCE THE PRICE IS
SIGNIFICANTLY HIGHER THAN THE
KINDS OF USUAL PATHOGENESIS
RESEARCH THAT YOU DO OR THAT I
DO IN ACADEMIA.
NEXT SLIDE.
SO FIRST THE WAY I DID IT AND
THEN I WILL JUST TOUCH ON THE
WAY A LOT OF OTHER IT IS DO IT,
I'VE GONE THROUGH THE
GOVERNMENT, SO I DORPHED THE
TARGET WITH RO-1, COULD ADD R35
GRANTS, I'VE DISCOVERED THE
CANDIDATE AGAIN WITH ANOTHER
SERIES OF GRANT AND THEN
TRANSITIONED INTO STTR,
FOUNDATION AND D.O.D. GRAPTS, I
RUN THE GAUNTLET WITH THOSE
GRANTS AT A HIGHER LEVEL AND I
PLAN ON DO THE CLINICAL TRIALS
WITH THE CLINICAL TRIALS AWARDS
FROM THE SAME AGENCIES, SO
THAT'S HOW I DID IT, THAT WAS MY
WAY BUT THERE'S AS YOU KNOW
SIGNIFICANT DELAYS, DOWN SIDES
AND PROBLEMS WITH THAT SOLE
GOVERNMENT FUNDING APPROACH
EMPLOY SO THEN THERE'S THE
PRIVATE WORLD.
NEXT SLIDE.
I WILL JUST HAVE 1 SLIDE ON THIS
FROM WHAT I'VE GLEANED FROM MY
DISCUSSIONS WITH VARIOUS VCs
AND PRIVATE INVESTORS, JUST A
QUICK LIST YOU COULD USE OR NOT
USE, TO GUIDE YOU HERE, SO FIRST
THEY'RE LOOKING FOR HIGH
QUALITY, DIFFERENT TECHNOLOGY,
ASSETS, HIGH LINE PLATFORM,
THAT'S ALL YOU GET OUT OF THE
FIRST COUPLE SLIDES I SHOWED
YOU.
THEY WANT COMPELLING DATA, THEY
WANT NEAR TERM CATALYSTS SO
THEY'RE IN THERE TO INCREASE
VALUE.
EVERYBODY WANTS TO GET TO HELP
PATIENTS THEY SAY BUT THEY'RE
ALSO LOOKING FOR CATALYST TO
RAISE THE VALUE OF YOUR PROJECT.
ONCE AGAIN, THE TIPS I GAVE YOU
WILL PROVIDE THAT INFORMATION.
STRONG IP, BE SURE YOU WORK OUT
CAREFULLY A MARKET STRATEGY AND
OPPORTUNITY.
DEFINITELY HAVE AN EXPERIENCED
MANAGEMENT TEAM, HOPEFULLY
PEOPLE WHO HAVE BEEN THERE AND
DONE THIS BEFORE EMPLOY THEY
LOVE TO SEE STAGES OF
DEVELOPMENT, IF YOU'RE NOT A G
ANTT LOVER ALREADY, YOU WILL
NEED TO BECOME 1 AND CONVINCE
PEOPLE OVER AND OVER THAT YOU'RE
ON TRACK AND THEY CAN TRACK YOU.
YOU WANT TO HAVE STRATEGIC
INTERESTS AND IDENTIFIABLE EXITS
IN ORDER FOR THEM TO SEE THE
VALUE AND INVESTMENT AND YOU
WOULD LIKE TO SHOW SOME SUPPORT
FROM LEADING INVESTORS.
THESE GUYS MOVE, NO OFFENSE
INTENDED HERE FOR ANYONE ON THE
CALL, THEY MOVE AS A HEARD, IT'S
A PENGUIN MENTALITY, 1
INVESTMENT FOLLOWS THE NEXT
INVESTMENT PERSON, SO IT'S GOOD
FOR YOU TO INCLUDE AT LEAST AS
BEST YOU CAN, SOME EVIDENCE OF
SUPPORT IN INVESTORS WHO SEEM TO
KNOW SOMETHING.
NEXT SLIDE.
ONE MORE.
THANK YOU.
SO TO RECAP, THAT WAS A LOT, A
LOT OF MILEAGE, A LOT OF ISSUES,
A LOT OF DETAILS.
SO RETURNING BACK TO THE BIG
PICTURE TO SOME UP, I'VE TRIED
TO GIVE YOU 5-POINTS HERE ALONG
THE JOURNEY THAT ARE KEY TO
GETTING TO THE GOAL, DORPHING
NEW CANDIDATE, DISCOVERING NEW
DRUG FOR THE CANDIDATE,
TRANSLATING THOSE FINDINGS INTO
MANUFACTURING AND SAFETY,
TRANSLATING THAT INFORMATION AND
ALL OF THAT INFORMATION ACTUALLY
INTO A PROPERLY DESIGNED PHASE
1-2 TRIALS AND HAVING SOME CLUES
AT LEAST INTO HOW TO FUND IT ALL
IN AN EFFICIENT WAY.
AND I WILL STOP THERE AND TURN
IT OVER TO THE NEXT PERSON.
THANK YOU.
>> THANKS DR. HOLTZMAN.
NEXT WE WILL HAVE D
R. ENRIQUE SHIAO WHO HEADS THE
SEARCH AND EVALUATION VENTURE
GROUP AT THE CF FOUNDATION WHICH
HAS BEEN LOOKING INTO 1 TIME
CURES AND OTHER THERAPIES FOR
CYSTIC FIBROSIS.
>> HI, EVERYONE EEXSEATED TO BE
AS PART OF THIS PANEL AND IN
GENERAL AS PART OF THIS
WORKSHOP.
THANKS AGAIN TO THE ORGANIZERS
FOR PUTTING THIS ALTOGETHER AND
DR. WEST AND DR. ZIADY FOR
MODERATING THE PANEL.
YOU'VE ALREADY HEARD ABOUT CF
TODAY, SO YOU'VE HEARD
INFORMATION AND KEY ADVANCES
AROUND MAN MALMODELS AND SOME
ASPECTS OF WHAT COULD CONSITUTE
A TARGET PROFILE IN CF AND I
WANT TO SPEND TIME TO INTRODUCE
THE CYSTIC PHOBEROSIS FOUNDATION
AND HOW YOU CAN PARTNER FROM
EARLY STAGE ACADEMIC WORK ALL
THE WAY TO THE CLINIC AND THEN
TO THE APPROVED PRODUCT.
NEXT SLIDE.
SO THE CF FOUNDATION HAS BEEN
AROUND FOR ALMOST 70 YEARS NOW.
WE WERE FIRST ESTABLISHED IN
1955 AT A TIME WHEN CF WAS
ALMOST SOLELY A PEDIATRIC
DISEASE.
TODAY BECAUSE OF TREATMENTS
AVAILABLE AND THE STANDARD OF
CARE ASSOCIATE WIDE CF, MANY
PEOPLE ARE LIVING INTO THEIR
LATE 50S AND BEYOND AND NEARLY
60% OF THE PEOPLE WITH CF ARE
NOW ADULTS.
IN TERMS OF MISSION OF THE CF
FOUNDATION IT IS TO CURE CF AND
PROVIDE ALL PEOPLE WITH CF THE
OPPORTUNITY TO LEAD LONG
FULFILLING LIVES BY FUNDING
RESEARCH AND DRUG DEVELOPMENT,
PARTNERING WITH THE CF COMMUNITY
AND ADVANCING HIGH QUALITY
SPECIALIZED CARE.
NEARLY ALL OF THE 16 APPROVED
THERAPIES HAVE BEEN APPROVED FOR
CYSTIC FIBROSIS WERE DEVELOPED
WITH THE FOUNDATION'S SUPPORT
AND TODAY THERE ARE MORE THAN
THE PIPE LENGTH TO ADDRESS THE
COST AND COMPLICATIONS OF THE
DISEASE.
NEXT SLIDE.
AND THEN, MORE BROADLY, WE ARE
IN A UNIQUE POSITION TO RISK AND
DECELERATE PROGRAMS THANKS TO
OUR WORK THROUGH PHILANTHROPY
AND OUR WORK AT THE COMMUNITY.
WE PLAN TO INVEST $3.5 MILLION
IN RND OVER THE NEXT FEW YEARS,
WE ARE NETWORK OF 100 + CENTERS
AND 47 MUSCULAR DYSTROPHY FTEs
AND BEST IN CLASS ASSAYS AND THE
LARGEST DATA BANK OF PATIENT
DERIVED CELLS AS WELL.
AND THEN WE'VE ALSO INVESTED IN
CF ANIMAL MODELS SOME OF WHICH
YOU HEARD TODAY, RODENTS,
FERRETS, PIG, SHEEP, AND ALSO
HAVE OUR BEST IN CLASS PATIENT
REGISTRY CAPTURING 90% OF THE
PATIENTS IN THE U.S., 90 + SITES
IN CF FOCUSED CLINICAL TRIALS
AND NETWORK, IN-HOUSE SCIENTIFIC
TEAM AND GLOBAL NETWORK OF
KOLs AND CLINICAL RESEARCH
DESIGN AND SUPPORT TEAM.
NEXT SLIDE.
IN TERMS OF HOW WE PARTNER WITH
TREY, WE HAVE,A PROACHS TO
INVEST IN CF PROGRAMS.
IT CAN BE AT PRODUCT BASES WITH
PRODUCT SPECIFIC ROALT GRAIMENTS
FOR LATE STAGE CLINICAL OR
COMMERCIAL PRODUCTS WE CAN ALSO
DO PREFERRED EQUITY SEED THROUGH
PRE-IPO, WHICH IS THE MOST
COMMON EARLY STAGE COMPANIES, WE
CAN ALSO DO COMMON EQUITY IN
PUBLIC COMPANIES, CONVERTIBLE
NOTES AND SAVES FOR BRIDGE
FUNDING AND HYBRID INVESTMENT
COMBINING APPROACH ANDS THEN
WE'RE ALSO LOOKING FOR
PARTNERSHIPS.
WE WORK OR WE CAN DO LIMITED
PARTNERSHIP INVESTMENTS, ALONG
THE INCUBATORS, NEW COMPANY
INFORMATION FOR SPECIFIC
APPLICATIONS AND THEN WORK IN
ACCELERATORS OR INCUBATORS TO
BRING NEW TECHNOLOGIES TO THE
CYSTIC FIBROSIS AND THE EXAMPLE
HERE IS TO THE GOLDEN TICKET WE
SPONSOR AT THE LABS AT BERKELEY.
NEXT SLIDE, PLEASE.
IN TERMS OF THE AREAS OF FOCUS,
ESPECIALENTIALLY IN THE GENETIC
THERAPIES, THE CYSTIC FIBROSIS
FOUNDATION IS REALLY LOOKING TO
ADDED TO THE NEED FOR THERAPIES
THAT MAY NEED HELP WITH
CYSTIC FIBROSIS, ESPECIALLY
THOSE THAT CANNOT TOLERATE
EXISTING TREEPS FOR EXAMPLE
MODULATORS AND WE ALSO BELIEVE
THAT GENETIC BASED THERAPIES ARE
KEY IN DEVELOPING A CURE FOR THE
DEC EMPLOY SO WHEN IT COMES TO
GENETIC MEDICINE THERE ARE 3 KEY
BUCKET WE'RE LOOKING FOR, THE
FIRST 1 IS PROTEIN RESTORATION.
WE'RE LOOKING FOR IMPROVEMENTS
OVER EXISTING RNA TECHNOLOGIES
THAT ARE CURRENTLY IN THE
CLINIC.
SO WE'RE LOOKING FOR EXAMPLE,
FOR OPPORTUNITIES THAT ALLOW US
TO READ THOSE APPROACHES
TARGETING THE LUNG, SYSTEMIC
APPROACHES THAT TARGET THE
LIVER, IMPROVE DURATION OR TIME
TO REDOSE, IN TERMS OF GENE
DELIVERY, WE RECOGNIZE THAT THE
LUNG IS HARD TO ACCESS AS YOU
HEARD TODAY, SO WE'RE LOOKING
FOR TECHNOLOGIES THAT CAN DO 1
OR MORE OF THE FOLLOWING TARGETS
ORIGINS, AS I MENTIONED LUNG IS
WHERE THE HIGHEST UNMET NEED IS
BUT WE'RE ALSO LOOKING AT
PANCREAS AND THE GI TRACT AND
THEN WITHIN THOSE ORGANS WE ARE
LOOKING AT SPECIFIC CELL TYPES
AND THEN WE'RE LOOKING FOR
TECHNOLOGIES THAT ALLOW US TO
READ THOSE OR DELIVER CARGO
SYSTEMICALLY AS WELL.
AND FINALLY FOR GENE EDITING WE
ARE LOOKING FOR APPROACHES TO
ALLOW US TO INSERT GENES INTO
RESTORE GENE FUNCTION AND THEN
MAKE EDITS WITH LITTLE
OFF-TARGETSMENT NEXT SLIDE,
PLEASE.
AND THEN THIS TERMS OF OFTEN
TIMES WITH THE DISEASE, THIS
MIGHT NOT BE THE KEY FOCUS OF
THE MEETING TODAY BUT I DID WANT
TO JUST TOUCH ON THIS AREA SINCE
IT IS AN AREA WHERE WE CONTINUE
TO MAKE INVESTMENTS,
SPECIFICALLY FOR SUITABLE
DIAGNOSING OF PATIENTS, WE ARE
LOOKING FOR IMPROVEMENTS FOR THE
TREATMENT OF CHRONIC
PSEUDONOAMON AS, AND ALSO
PULMONARY INFECS ASSOCIATE WIDE
BURKHOLDERRIA SPECS AND ALSO
METHODS FOR PULMONARY METHODS
THAT DON'T RELY ON SPUTUM WITH
PSEUDOMONAS SCREENINGS AND THEN
FOR OTHER DIAGNOSE.
WE'RE ALSO LOOKING FOR MAJOR
IMPROVE AMS IN TREATMENTS FOR
OTHER COMMON PATHOGENS AFFECTING
PEOPLE WITH CYSTIC FIBROSIS.
NEXT SLIDE, PLEASE.
AND THEN HERE, I JUST ALSO
WANTED TO TOUCH REALLY BRIEFLY
ON MANY OF THE CHALLENGES THAT
WE HEARD MENTIONED TODAY AROUND
FUND XG AROUND MOVING A COMPANY
FORWARD, REALLY AMPLIFIED IN THE
CASE AND THE ANTIMICROBIAL
PROJECTS WHICH HAS AS I
MENTIONED MAYBE NOT BEEN THE
FOCUS TODAY BUT I WANT TO PLUG
THIS CONTINUES TO BE AN
IMPORTANT AREA FOR US AND HERE
WE PARTNERED CLOSELY WITH THE
NIH AND OTHER PROGRAMS FOR
EXAMPLE, THAT STEPHANIE DAVIS
MENTIONED AND OTHER PUBLIC
ENTITIES TO MOVE THERAPIES IN
THIS SPACE FURTHER.
NEXT SLIDE, PLEASE.
AND THEN BEYOND THIS DIRECT WAYS
IN WHICH WE ENGAGE COMPANIES WE
ALSO PROVIDE CLEAR GUIDANCE WHEN
IT COMES TO THE PRECLINICAL OR
EARLY STAGE DEVELOPMENT AND I
WANTED TO SHOW EXAMPLES FROM MY
COLLEAGUES, [INDISCERNIBLE] FROM
THE FOUNDATION, AS WELL AS JOHN
WHO IS HERE TODAY AS WELL.
NEXT SLIDE, PLEASE.
THIS IS AN SAMPLE DOCUMENT THAT
WE PROVIDE COMPANIES IN THE
MEDICINE SPACE.
IT DETAILS DIFFERENT ASSPEBTS
THAT ARE IMPORTANT WHEN YOU'RE
THINKING ABOUT FOR EXAMPLE,
HERE, A PRECLINICAL PACKAGE OR A
TRANSIENT THERAPY FOR REPEAT
DOSING WHAT ARE THE
CHARACTERISTICS YOU HAVE TO
THINK ABOUT AND WHAT ARE SOME OF
THE KEY AREAS WHERE SPECIFIC
ASSAYS THAT WERE DEVELOPED OR
THAT ARE DEVELOPED COULD HELP
YOU ANSWER SOME OF THE OPEN
QUESTIONS HERE.
NEXT SLIDE, PLEASE.
AS I MENTIONED AS WELL, WE ALSO
PROVIDE GUIDANCE IN TERMS OF
WHAT ARE THE KEY IN VIVO MODELS
THAT -- AS WELL AS CELL MODELS
IT CAN USE TO VALIDATE
TECHNOLOGIES, SOME OF WHICH WE
HAVE IN OUR LABS IN BOSTON, AND
THEN SOME OF THE MODELS THAT WE
HAVE THROUGH OUR PARTNERS, AND
THEN WE'RE HAPPY ALWAYS TO WALK
COMPANIES THROUGH WHAT ARE THE
DIFFERENT MODELS OUT THERE,
WHICH 1 IS MOST APPROPRIATE FOR
TECHNOLOGY THAT YOU'RE
DEVELOPING, AND WHICH 1S ARE
CRUCIAL WHEN YOU'RE THINKING
ABOUT PREPARING YOUR IND
PACKAGE.
NEXT SLIDE, PLEASE.
AND THEN THE NEXT 3 SLIDES
REALLY JUST FOCUS ON SOME OF THE
KEY ASSAYS THAT WE'VE DEVELOPED,
BUT THEN, WE ALSO THINK OUR CREW
[INDISCERNIBLE] WHEN YOU'RE
PREPARING THAT PACKAGE FOR THE
FDA AND ALSO FOR THE NETWORK TO
ASSESS THE VALIDITY OF YOUR
TECHNOLOGY.
SO I WON'T WALK YOU THROUGH ALL
OF THIS BUT THIS IS JUST AN
EXAMPLE OF THE DOCUMS THAT WE'RE
HAPPY TO PROVIDE OUR PARTNERS,
IF YOU'RE THINKING ABOUT THE
PPP AND CYSTIC FIBROSIS.
WE CAN SKIP TO THE NEXT SLIDE
AND THE NEXT.
NEXT SLIDE.
AND NEXT SLIDE, PLEASE.
AND THEN, FINALLY BECAUSE THE
TITLE OF THIS WORKSHOP IS FROM
CONCEPT TO CLINIC, I DID WANT TO
TOUCH ON ACADEMIC FUNDING
OPPORTUNITIES, WE HAVE A
PROLIFIC PORTFOLIO AND
MECHANISMS THAT CAN EXPLORE
PROGRAMS THAT CAN LEAD TO
COMPANY IDEAS.
IF YOU GO TO THE NEXT SLIDE.
SO OUR STANDARD FUNDED
MECHANISMS ARE RESEARCH GRANT, 3
YEARS, 150 K DIRECT PER YEE,
PLUS INDIRECT, PRELIMINARY DATA
REQUIRED.
NEXT SLIDE.
WE ALSO HAVE PILOT SIMULATED
GRANTS, 2 YEARS, 50 K PER YEAR,
PLUS [INDISCERNIBLE] PERCENT
DIRECT.
THAT'S NOT REQUIRED FOR THAT.
AND ALSO OFFER POST DOCTORAL
FELLOWSHIPS, 2 YEAR DURATION, 76
K IN YEAR 1 AND 76 IN YEAR 2.
NEXT YEAR AND THEN FINALLY WE
HAVE POST DOC FACULTY TRANSITION
AWARDS SIMILAR TO K99S, FUNDING
POST THE BOACT DOC PHASE AND THE
FACULTY PHASE.
APPLICATIONS ARE ACCEPTED IN
DECEMBER ONLY BUT IN GENERAL OUR
APPLICATION CYCLES ARE IN MAY
AND DECEMBER.
NEXT SLIDE.
AND THEN FINALLY WHEN IT COMES
TO PATH CHECK HERE WE HAVE
SPECIAL FUNDING MECHANISMS, FOR
EXAMPLE, OUR GOAL SUPPORT
INTEGRATED MULTIINVESTIGATOR
RESEARCH PROBABLES WITH THE
WELL-DEFINED CENTER OF FOCUS,
THIS IS UP TO 3 YEARS WITH
1 MILLION DIRECT PLUS 12%
INDIRECT FUNDING, RECEIPT DATE
IS JULY 29th.
NEXT.
AND THEN WE ALSO HAVE THE PIE O
NEAR AWARDS WITH THE GOAL TO
SUPPORT PARADIGM SHIFT IN
TECHNOLOGIES THAT HAVE THE
POTENTIAL TO CURE CF AT THE
CELLULAR OR THE GENETIC LEVEL
AFTER 3 YEARS AND FUNDING AS
AGREED UPON PLUS, 12% INDIRECT
ROLLING BASIS RECEIVE DATE AND
THIS 1 IS SIMILAR TO SOME OF THE
DISCUSSION WE HEARD IN THE PAST
PANEL AROUND RO-1S AND HOW
THEY'RE BEING USED TO THINK
ABOUT SOME OF THIS NEW
THERAPIES.
NEXT SLIDE.
SO YEAH, IN GENERAL, THE CFF IS
HERE REALLY TO PROVIDE
RESOURCES, THANK YOU SO MUCH
DR. HOLTZMAN, FOR MAKING THAT
PATH TOWARDS A THERAPEUTIC AND
WE'RE REALLY HOPING HERE TO BE
ABLE TO PROVIDE THE RESOURCES
THAT OUTLINED AS PEOPLE ARE
THINKING ABOUT CYSTIC FIBROSIS
AS AN INDICATION AND THEN IF YOU
ARE LOOKING FOR ADDITIONAL
INFORMATION, FEEL FREE TO
CONTACT ME OR VISIT THESE 2
SITES.
THANK YOU VERY MUCH.
>> THANKS DR. SHIAO.
>> SO OUR NEXT SPEAKER WILL BE
LUCY LIU, FROM THE LONG WOOD
FUND IN BOSTON AND SHE WILL
SHARE THEIR PRESENCE WITH
VENTURE CAPITAL THERE AND THE
STEPS THAT PEOPLE GO THROUGH TO
INTERACT WITH THEM AND THE
INVESTMENTS THEY MAKE WITH NEW
PATIENTS.
>> THANK YOU SO MUCH FOR THE
MODERATORS AND ALSO FOR THE
OPPORTUNITY TO SPEAK WITH
EVERYONE HERE TODAY.
WOULD LOVE TO PROVIDE AN
OVERVIEW OF HOW EARLY STAGE
VENTURE PERSPECTIVE, WE LOOK AT
BOTH ASSETS TO START A COMPANY
AND IF A COMPANY EXISTS AROUND
YOUR PARTICULAR TECHNOLOGY, THE
LINES WE HAVE AT EARLY STAGE
INVESTORS AND THINKING ABOUT
INVESTING OPPORTUNITIES THAT
WILL EVENTUALLY BECOME A DRUG,
SO I HAVE A FEW SLIDES HERE TO
HELP CONTEXTUALIZE MY
BACKGROUND, LONG BACKGROUND AND
HOW WE VOW THE WORD AS VENTURE
INVESTORS SO OFTEN TIME FIST YOU
INTERACTED WITH ANY OF US, THE
INTERACTIONS ARE LIKELY A LITTLE
BIT [INDISCERNIBLE].
SO ON THE NEXT SLIDE, PLEASE,
WANTED TO HIGHLIGHT HOW WE VIEW
THE WORLD WHICH IS THAT WE PRIDE
OURSELVES ON BUILDING BIOTECHS
THAT CREATE DRUGS THAT HAVE A
LASTING IMPACT AND COVER HIGH
UNMET NEEDS.
WHAT I AM SHOWING ARE A FEW
EXAMPLES OF COMPANIES THAT ALONG
WITH PARTNER VS STARTED.
ALL OF THESE STARTED WITH AN
[INDISCERNIBLE] LAB AND WITH 10
+ YEARS OR MORE THAN THAT AND
MILLIONS IF NOT BILLIONS IN
INVESTMENTS, THESE IDEA ANDS
CONCEPTS HAVE TURNED INTO OVER
20 DEFINITE MARKETED PRODUCTS,
AND ADDITIONAL THERAPIES AND
LATE STAGE DEVELOPMENT.
OT BOTTOM HERE HIGHLIGHTING A
FEW OF THE DRUGS THAT ALONG LONG
WOOD COMPANIES HAVE DEVELOPED
AND YOU KNOW 20 YEARS AGO
STARTED OUT AS A EXPERIMENT AND
EVENTUALLY IN A UNIVERSITY
SOMEWHERE.
SO ON THE NEXT SLIDE, PLEASE, 1
THING THAT I THINK WHAT NEEDS TO
BE QUITE CLEAR AND WHAT WE THINK
ABOUT DEEPLY IS THAT DRUG
DEVELOPMENT IS VERY EXPENSIVE IS
TAKES A VERY LONG TIME.
SO WE ALWAYS THINK ABOUT THE
PARTNERS THAT WE WILL HAVE TO
GET US THERE, GENERALLY IN TERMS
OF BIOTECH VENTURE CAPITAL,
WE'RE SPLIT INTO EARLY STAGE
GROWTH STAGE AND THEN
ESSENTIALLY GOING TO PUBLIC
INVESTORS AND THINGS GOING
BEYOND THERE.
AS EARLY STAGE INVESTORS, WE
THINK DEEPLY ABOUT THE PARTNERS
THAT HELP US GET THERE, I HAVE
LISTED SOME EXAMPLES HERE OF CO
INVESTORS THAT HAVE A SIMILAR
MIND SET TO US.
SO REALLY ON THE INVESTORS
GENERALLY TEND TO FLOCK
TOGETHER.
IT'S TRUE BECAUSE AT A VERY
EARLY STAGE OF THE COMPANY,
THERE WILL BE MANY DIRECTIONS
FOR THE TECHNOLOGY OR FOR THE
PLATFORM TO GO.
AND THOSE EARLY DECISIONS HELP
REALLY CRAFT THE PATH THAT YOUR
MOLECULE OR THAT YOUR PLATFORM
WILL TAKE TO DRIVE IT TOWARDS
SOMETHING MEANINGFUL.
AND THEN AT THE SAME TIME, WE'RE
VERY MUCH AWARE THAT EARLY
STAGES OF DEVELOPMENT, SMALL
COMPANY, YOU CAN GET STARTED ON
PRECLINICAL STUDIES, MAYBE YOU
CAN GO THROUGH YOUR EARLY PHASE
1 OR PHASE 2, BUT THEN GETTING
TO LATE STAGE DEVELOPMENT, IT'S
IMPORTANT THAT MOST OF THE TIME,
JUST GIVEN THE NUMBER OF
PATIENTS THAT YOU NEED TO
RECRUIT AND THE DURATION OF
CLINICAL STUDIES, THERE NEEDS TO
BE A STRATEGIC PARTNER SO IN
THIS CASE A PHARMA OR OTHER TO
REALLY HELP FINANCE THE REST OF
THE STUDIES AND THEN EVENTUALLY
BRING IT TO COMMERCIALIZATION.
AND THEN IN THE LAST BUCKET,
SCIENCE IS ALWAYS UNPREDICTABLE
AND WE LIKE TO WORK WITH
ACADEMICS THAT HELP REALLY SHAPE
OUR COMPANIES THAT WE BUILD AND
ALSO PROVIDE THE INITIAL
CATALYST THAT START A PARTICULAR
CONCEPT, SO JUST HIGHLIGHTING
SOME OF THE INSTITUTES THAT
WE'VE WORKED WITH, AND ALSO
WHERE LONG WOOD FOLKS HAVE
TRAINED TO REALLY START AND STEP
1 AS A CONCEPT TO BUILD A
COMPANY AROUND.
NEXT SLIDE, PLEASE.
SO TO GIVE YOU A SENSE OF THE
TEAM AND THIS -- THE TEAM THAT
WE CAPTURE AT LONG WOOD IS QUITE
SIMILAR IN PROFILE TO OTHER
TEAMS THAT YOU WILL FIND OTHER
COMPANY CREATION FIRMS AROUND
THE COUNTRY AND SO WHAT I'M
HIGHLIGHTING HERE IS THAT WE'RE
GENERALLY A VERY SMALL TEAM.
THERE'S 7 OF US IN THE
INVESTMENT TEAM, FIRST OFF WEST
FALL IS A CONFOUNDER AND OUR
GENERAL PARTNER, AND HE IS
BEHIND A NUMBER OF COMPANIES
WHERE HE WAS THE INITIAL
CONFOUNDER WITH AN ACADEMIC AND
ALSO THE INITIAL CEO TO HELP
BUILD OUT THESE COMPANIES.
AND THEN, THOSE ADDITIONAL TEAM
MEMBERS, ALEX WHO'S 1 OF THE
PARTNERS, AND 1 OF THE VENTURE
PARTNERS AND THE REST OF US ON
THE INVESTMENT TEAM, WE ALL WORK
TOGETHER TO CRAFT AREA ARES OF
FOCUS THAT WE LIKE TO DUE A DEEP
DIVE ON AND THEN START WORKING
AS A SMALLER GROUP ON COMPANY
CREATION.
SO IF WE -- IF YOU EVER SEE AN
E-MAIL FROM 1 OF US REACHING OUT
TO YOU TO TALK ABOUT A
PARTICULAR OPPORTUNITY OR TO GET
YOUR THOUGHTS ON AN AREA WHERE
WE WOULD LIKE TO GET A LITTLE
BIT DEEPER INFORMATION ON,
YOU'LL PROBABLY KNOW THAT IT'S
GENERALLY FOR US TO EVALUATE
WHETHER WE WANT TO START A
COMPANY IN A PARTICULAR AREA AND
WHETHER YOU WOULD HAVE
INTERESTING TECHNOLOGIES THAT WE
SHOULD BE DISCUSSING TO START
THESE COMPANIES.
AND SO 1 THING THEY WANT TO
POINT OUT IS THAT AS EARLY STAGE
COMPANY CREATORS AND INVESTORS,
ALL OF US PRIDE OURSELVES ON
BEING SCIENTISTS AT SOME POINT,
MANY OF US, YOU WILL SEE ON THE
TEAM HERE, HAVE PH Ds OR POST
DOCS OR BOTH.
AND REALLY PRY OURSELVES ON
BEING ABLE TO, IF WE NEEDED TO,
ALTHOUGH, GENERALLY PROBABLY
DON'T WANT US THERE, GO BACK ON
THE BENCH AND RUN AN EXPERIMENT
OR AT LEAST DESIGN, EXPERIMENTS
FOR CROs TO BE ABLE TO DO.
SO WE REALLY STRADDLE BOTH
SCIENTIFIC ASPECT OF EARLY STAGE
EXPERIMENTS THAT WE THINK WILL
GENERATE VALUE, TO VALIDATE THE
TECHNOLOGY AS WELL AS THE
BUSINESS SIDE OF THINGS TO MAKE
SURE THAT THE COMPANY IS BUILT
ON A SUSTAINABLE BASIS FOR THE
LONG-TERM.
SO ON THE NEXT SLIDE, NEXT
SLIDE, PLEASE, I WOULD LIKE TO
GIVE YOU A ERROR HIGH LEVEL VIEW
OF IF YOU HAVE AN ASSET, OR IF
YOU HAVE A PLATFORM TECHNOLOGY,
HOW IF YOU BRING IT TO A BIOTECH
VEBTURE FUND, HOW THEY WOULD
EVALUATE YOUR ASSET OR
TECHNOLOGY.
THIS OF COURSE IS NOT APPLICABLE
TO EVERY SINGLE TYPE OF
TECHNOLOGY BUT JUST TO IMIF YOU
A SENSE OF HOW WE VIEW
EVERYTHING, THERE'S DEPENDING ON
THE STAIM THAT YOU'RE AT,
ASSUMING PRECLINICAL, THE
BUCKETS THAT WE CARE A LOT ABOUT
FOR 1 IS, IF THERE IS A
PARTICULAR ASSET, IT'S REALLY
THE DISEASE BIOLOGY, AND JUST
KIND OF GOING THROUGH HOW
BIOTECH THINKS ABOUT THINGS, 1
THING IS OF COURSE IS THE DEC
WELL DEFINED AND BY THAT I MEAN,
HAVE THERE BEEN PRIOR STUDIES
AROUND THIS PARTICULAR DISEASE,
DO WE UNDERSTAND THE BLACK AND
WHITE NATURE OF HOW DO YOU KNOW
IF YOU'RE SICK, WHAT'S THE
DEMARCATION BETWEEN HAVING I
GUESS FULLY HAVING A PARTICULAR
DISEASE VERSUS NOT, AND THEN
HAVING DIFFERENT TYPES OF
CONVICTION TO PERHAPS STRATIFY
YOUR PATIENT POPULATION SO YOU
CAN -- YOUR DRUG COULD BE ARK
PLIED TO THE PATIENTS THAT WILL
MOST LIKELY SHOW A RESPONSE, SO,
IN THAT CASE WE OFTEN THINK
ABOUT HUMAN GENETICS OR IF
THERE'S OTHER WAYS FOR US TO
PARSE PATIENTS INTO DIFFERENT
CATEGORIES.
ONE THING IN ADDITION TO THAT
JUST GOING BEYOND DEC BIOLOGY IS
UNDERSTANDING IF THERE'S A GOOD
MODEL, WHETHER INVITRO OR IN
VIVO, FOR US TO BETTER
UNDERSTAND THE DISEASE AND
WHETHER OR NOT YOUR KRUG IF IT
WORKS IN A DISH, IT WILL WORK IN
A PERSON.
THAT'S OF COURSE A VERY HIGH BAR
AND I WILL SAY AS A PRIOR
TRAINED NEUROSCIENTIST, THERE'S
VERY FEW GOOD MODELS OF
NEURODEGENERATIVE DISEASE FOR
EXAMPLE, BUT IN THE CASE OF
CYSTIC FIBROSIS, THERE'S A
FANTASTIC INVITRO MODEL DISEASE
THAT REALLY GIVES YOU INSIGHT
INTO HOW A DRUG COULD WORK AND
YOU KNOW THAT OF COURSE DRIVES A
LOT OF WHERE YOU SEE MORE DRUG
DISCOVERY FOR AREAS OF UNMET
NEED.
AND THEN, IN TERMS OF ADDITIONL
THOUGHTS, THE WAY THAT EARLY
BIOTECH VENTURE GROUPS THINK IS
REALLY ON THE CLINICAL
DEVELOPMENT WHICH THEN BUILDS
INTO THE LAST ROW HERE WHICH IS
COMPANY BUILD.
ONE ASPECT IS THAT THESE
COMPANIES, YOU RAISE VERY SMALL
AMOUNTS OF CAPITAL ASK THEN YOU
END UP RAISING MORE AND MORE
MONEY AS YOU'RE CLOSER TO THE
CLINIC OR YOU'RE ALREADY IN THE
CLINIC.
AND SO, 1 THING THAT YOU WILL
PROBABLY NOTICE IS THAT THERE'S
FEWER BIOTECHS WORKING ON VERY,
VERY LARGE INDICATIONS, WHICH IN
A SENSE IS KIND OF A MAJOR
LIMITATION THAT THE FIELD HASN'T
REALLY SOLVED.
SO VERY FEW BIOTECHS WORKING ON
HEART FAILURE FOR EXAMPLE, GIVEN
THAT IT'S A VERY LARGE AND
HETEROGENEOUS POPULATION.
IT WILL TAKE MANY YEARS ISSUES
IT'S DIFFICULT TO GET THAT FIRST
PROOF OF CONCEPT.
AND THEN, AT THE SAME TIME ASIDE
FROM CLINICAL DEVELOPMENT WE DO
WANT TO HAVE A VIEW ON WHAT DOES
SUCCESS LOOK LIKE, WHAT IS A
MARKER YOU NEED TO REACH OR WHAT
IS SOMETHING THAT CAN TELL YOU
OR HELP YOU, PUSH YOU TOWARDS
THE LIKELIHOOD OF SUCCESS
TOWARDS THE POSITIVE END.
AND THEN, AT THE SAME TIME,
COMPETITION, OF COURSE, THIS IS
SOMETHING THAT'S A LITTLE BIT
MORE DIFFICULT TO STRICTLY
QUANTIFY BUT 1 ASPECT IS FOR
EXAMPLE, STANDARD OF CARE AND
WHETHER EVERY SINGLE TREATMENT
FOR EXAMPLE, IS ALREADY ALL
PATENT, COST PENNY SAYS, MAYBE
THERE'S SOME UNMET NEED LEFT BUT
NOT TERRIBLY MUCH, YOU CAN
IMAGINE HOW IF THAT'S A NO
ACROSS THE BOARD, OR A YES
ACROSS THE BOARD, IT BECOMES
MUCH MORE DIFFICULT FOR EARLY
STAGE INVESTORS TO GET EXCITED.
AND THEN, EVERYTHING ELSE KIND
OF GOES INTO THE ADDRESSABLE
MARKET AND THE PRICE OF YOUR
POTENTIAL DRUG DOWN THE ROAD AND
HOW MANY PEOPLE IT WILL HELP AND
SO, REALLY PUTTING EVERYTHING
TOGETHER, YOU WILL SEE THAT
THERE IS MAYBE A PARTICULAR
NICHE THAT BIOTECH INVESTORS
FOCUS ON AND SO FOR ANY ASSET OR
PLATFORM TECHNOLOGY THAT YOU MAY
BE DEVELOPING, YOU CAN SEE HOW
THERE'S PERHAPS A WAY TO EITHER
TAYLOR THE RESEARCH OR WEAVE
YOUR STORY.
SO THERE'S MULTIPLE YESS FOR THE
FIRST FEW BUCKETS, AND AS WELL
GETTING A SENSE OF HOW MANY
YEARS IT WILL TAKE FOR YOUR
PARTICULAR PROGRAM TO GET TO A
STAGE THAT VALIDATES SOMEONE'S
INVESTMENT.
AND YOU KNOW ON THE RIGHT HAND
SIDE JUST KIND OF HIGHLIGHTING
THAT IF THERE'S MULTIPLE NOs
OF A LIMITING INTEREST AND THEN,
IF THE ANSWERS, I DON'T KNOW
THAT ALSO MAKES THINGS A LITTLE
BIT MORE DIFFICULT.
BUT IN SPEAKING WITH VENTURE
CREATION TYPE OF FUNDS AS OPPOSE
TO JUST VENTURE INVESTORS,
GENERALLY, IF THE TECHNOLOGY IS
VERY INTERESTING, AND COULD
UNLOCK SOMETHING SPECIAL,
VENTURE GROUPS WOULD LIKE TO
HAVE JUST AN OPEN BRAINSTORM
TYPE OF CONVERSATION TO
UNDERSTAND WHERE YOUR TECHNOLOGY
COULD BE APPLIED SO IT'S
DEFINITELY, YOU NEED TO DO ALL
THIS WORK YOURSELF AHEAD OF TIME
BEFORE TALKING TO SOMEONE, IT'S
REALLY A -- LET'S BRAINSTORM AND
FIGURE OUT WHERE THEIR COULD BE
APPLICATIONS AND SO, THOSE OF US
AT LONG WOOD AND IN GENERAL MOST
CREATION VENTURE FUNDS ARE HAPPY
TO HAVE THAT CONVERSATION JUST
AS A BRAINSTORM BECAUSE AT THE
SAME TIME FOR US, IF SOMETHING'S
NOT READY NOW IT DOESN'T MEAN
THAT IT'S NEVER GOING TO BE
READY.
EVERYTHING IS TIMING DEPENDENT.
SO WITH ALL OF THAT SAID, NEXT
SLIDE, PLEASE.
I WANT TO GIVE JUST A VIEW INTO
HOW WE'VE APPLIED THIS IN THE
PAST.
SO, TO GIVE YOU A TANGIBLE
EXAMPLE, THERE'S I THINK SEVERAL
PEOPLE FROM CARBON BIOSCIENCES
HERE, THIS A COMPANY THAT WE
BUILT 2 YEARS AGO CONFOUNDED,
PROFESSORS JOHN INGLE HATTER AND
ROCK COTTON AND TOO KIND OF
BRING YOU ALL THE WAY BACK.
ONE OF THE AREAS WE HAD FOCUSED
ON, MAYBE 3 YEARS AGO, WAS
WANTING TO START AN EXPLORATION
AROUND GENE DELIVERY OR EFFORTS
AROUND HOW 1 DELIVERS A GENE.
THIS QUICKLY FOR US SORTED INTO
A FEW DIFFERENT CATEGORIES, SO
IN THE WORLD OF GENE DELIVERY,
THERE'S OF COURSE VIRAL,
NONVIRAL, THERE'S ALSO THINKING
DEEPLY ABOUT WHETHER IT'S THE
CALCIT OR ENVELOPE OR THE CARGO
ITSELF.
AND GENERALLY FOR A NEW COMPANY,
WE LIKE TO ARE 1 AREA OF
INNOVATION THAT WE REALLY FOCUS
ON WHERE EVERYTHING ELSE KIND OF
AT AS MORE MAYBE TRADITIONAL OR
STANDARD OR WELL-VALIDATED.
SO IN PARSING OUT THE WORLD INTO
THESE 4 CATEGORIES, WE STARTED
THINKING ABOUT, NOT JUST WHO WE
COULD TALK TO TO DISCOVER MORE
ABOUT THESE TECHNOLOGIES AND
APPROACHES, BUT MORE SO ON IF WE
HAD THE IDEAL, WHETHER IT'S
CARGO OR ENVELOPE OR VIRAL OR
NONVIRAL APPROACH, WHAT IS A
DISEASE THAT COULD BE APPLICABLE
HERE WHERE WE WOULD FIT MANY OF
THE CRITERIA ON THE PRIOR SLIDE
THAT I MENTIONED.
WHERE THE DISEASE IS WELL
UNDERSTOOD, THERE'S BIOMARKER OR
NATURAL HISTORY OR OTHER METRICS
FOR US TO KNOW WHAT GOOD LOOKS
LIKE AND THEN AT THE SAME TIME
HAS A HIGH UNMET NEED FOR US TO
REALLY BE ABLE TO FIND PATIENTS
IN A REASONABLE AMOUNT OF TIME
TO SHOW SIGNS OF EFFICACY.
SO KIND OF MOVING THROUGH THE
EVALUATION AND SPEAKING WITH A
NUMBER OF SCIENTISTS WORKING IN
DIFFERENT AREAS OF BIOLOGY, WE
TRIANGULATED ON 2 THINGS.
WE TRIANGULATED ON THE
[INDISCERNIBLE] TECHNOLOGY BEING
DEVELOPED AT THE ENGLAND
JOURNALLE HEART LAB AND THIS WAS
ALSO GEARED TOWARDS
CYSTIC FIBROSIS.
THIS IS EXCITING FOR US BECAUSE
IN THE WORLD OF THINKING ABOUT
CYSTIC FIBROSIS AS ENRIQUE JUST
MENTIONED IN THE PRIOR PANEL
THIS,
THIS IS A DISEASE THAT HAS VERY
WELL UNDERSTOOD GENETICS,
INVITRO MODELING THAT GIVES YOU
A SENSE OF WHAT SUCCESS COULD
LOOK LIKE AND THERE'S ALSO A
DEEP UNDERSTANDING OF YEEN
THERAPY AND WHAT BOCA VIRUSES
WHICH HAS A LARGER
CARBOCAPACKITY COULD OPEN UP FOR
DISEASE WHERE EXISTING
APPROACHES HAVE VERY SMALL
TRUNCATED VERSIONS OF THE
CYSTIC FIBROSIS GENE BEING
DELIVERED WHICH HAS ITS JUST
BIOLOGICAL LIMITATIONS GIVEN
THAT IT'S SYNTHETIC TO AN
EXTENT.
AND SO ALL OF THESE THINGS
CULMINATED IN US GETTING EXCITED
ABOUT A PRIMARY ARCS SET AND
THEN AT THE SAME TIME WE ALWAYS
KNOWING THAT IN EARLY STAGE
THERE'S A HIGH FAILURE RATE WE
WANT THERE TO BE A PLATFORM
TECHNOLOGY THAT ALLOWS US TO
BUILD MULTIPLE OTHER PROGRAMS
THAT HAD A SIMILAR THESEIS
AROUND IT SO THAT'S WHAT ALLOWED
US TO BRING IN TECHNOLOGIES FROM
ROB COTTON, WHERE THERE'S A
NUMBER OF DIFFERENT PARVE O
VIRUSES THAT HAVE SIMILAR
FEATURES TO BOCA VIRUS THAT CAN
ALL BE MANUFACTURED IN A SIMILAR
WAY EMPLOY SO, IN ALL OF THIS,
WE ENDED UP DECIDING TO GO
FORWARD WITH A COMPANY BUILD
EMPLOY BUILD -- FIND A GROUP OF
INVESTOR WHO IS ARE LIKE MINDED
AND SEE THE VALUE IN THIS NOVEL
WAY OF APPROACHING GENE DELIVERY
BUT STILL MAINTAINING THE
SIMILAR STRUCTURE OF HOW THINGS
WILL BE DONE.
FOR EXAMPLE, MANUFACTURING
REMAINS NEARLY THE SAME AS
EXISTING PRIOR APPROACHES AND
THESE REALLY MATTER FOR TALKING
TO PHARMAS AND OTHER GROUPS WHO
WILL HELP WITH THAT LATER STAGE
DEVELOPMENT AND
COMMERCIALIZATION OF A POTENTIAL
PRODUCT.
SO YOU KNOW, THIS IS OF COURSE
MANY MONTHS OF WORK FROM A
COMPRESSED AND CONDENSED INTO A
SINGLE SLIDE BUT HOPEFULFULLY
THAT'S TANGIBLE VIEWING TO HOW
COMPANIES REALLY GET STARTED AND
1 APPROACH FROM, YOU KNOW THE
VENTURE SIDE OF HOW WE START
COMPANIES WHICH COULD BE A
LITTLE BIT DIFFERENT THAN HOW
OTHER GROUPS OR OTHER TYPES OF
COMPANY CREATION KIND OF OCCURS.
SO NEXT SLIDE, PLEASE.
TO REALLY WRAP IT UP, I WANT TO
JUST HIGHLIGHT THAT IN THE WORLD
OF NEW CO CREATION FROM A
VENTURE PERSPECTIVE, I'M JUST
HIGHLIGHTING THE COMPANIES THAT
WE HAVE INVESTED IN AND THAT WE
HAVE BUILT, THE 1S THAT HAS THE
GREEN BOX ON THE BOTTOM OR 1S
THAT WE'VE CONFOUNDED, I THINK
IN NEARLY ALL OF THESE CASES,
WITH AN ACADEMIC FOUNDER AS THE
SCIENTISTS, KEY SCIENTISTS
BEHIND THESE TECHNOLOGIES AND
THAT'S ESSENTIALLY THE MAIORITY
OF WHAT WE DO, WE LOOK FOR
EXCITING NOVEL BIOLOGY OR
EXCITING NEW TECHNOLOGY THAT CAN
SERVE TO TRANSFORM A PARTICULAR
AREA OR UNLOCK SOMETHING UNIQUE
TO GIVE US AN ANGLE INTO THE
MARKET AND YOU KNOW I THINK FOR
US, WHEN WE SEEK OUT TO MEET AND
TALK TO DIFFERENT WHETHER IT'S
PROFESSORS OR LICENSING GROUPS
OR OTHERS, IT'S REALLY JUST A
BETTER UNDERSTAND THE STATE OF
THE CURRENT FIELD AND ALSO TO
GATHER A GROUP OF LIKE MINDED
SCIENTISTS WITH A SIMILAR GOAL
IN MIND, TO BRAINSTORM AND SEE
IF THERE'S SOMETHING THAT WE CAN
BUILD TOGETHER.
SO HOPEFULLY, THAT GIVES YOU A
SENSE OF HOW, AT LEAST MOST OF
US AT LONG WOOD AND EARLY STAGE
VENTURE CREATION FIRMS THINK
ABOUT TECHNOLOGIES AND THINK
ABOUT COMPANY CREATION AND SOME
EXAMPLES OF COMPANIES WE'VE
BUILT IN THE PAST THAT ARE BEEN
SUCCESSFUL AND BROUGHT DRUGS TO
PATIENTS.
AND IF ANY OF YOU WOULD LIKE TO
TALK ABOUT COMPANY CREATION OR
TALK ABOUT YOUR TECHNOLOGY
YOU'RE DEVELOPING WHETHER
THERE'S IP BEHIND IT, MAYBE A
PAPER ABOUT TO BE PUBLISHED,
PLEASE REACH OUT, WOULD LOVE TO
HAVE THAT CONVERSATION.
>> THANK YOU VERY MUCH.
THE FINAL SPEAK OF THIS SERIES
WILL BE DR. BENOIT, HE HAS WITH
MDI THERAPEUTICS HE WILL SPEAK
ON START-AUTOPSIES AND COMPANIES
IN THE PHARMACEUTICAL
INDUSTRIES.
>> THANK YOU.
APPRECIATE IT.
HOPEFULLY YOU CAN ALL HEAR ME
WELL ENOUGH.
ALSO HAPPY TO HAVE MY HONORARY
DOCTORAL ISSUED AGAIN, TODAY,
THAT'S GOOD.
I'M STILL HAPPY JUST TO BE ABLE
TO SPELL Ph.D., SO, STILL
WORKING FROM THE BUSINESS SIDE.
ALONG WITH MY COLLEAGUES FROM
UNIVERSITY OF MICHIGAN.
NEXT SLIDE, PLEASE.
I WAS ASKED TO SORT OF GIVE YOU
A SENSE FOR HOW WE COMBINE BOTH
SEED CAPITAL, NIH FUNDING AND
VENTURE FUNDING TO GET OUR FIRST
ASSET INTO THE CLINIC AND SO,IME
GOING TO KIND OF START AT THE
BACK END WHICH GIVES YOU A QUICK
IDEA, WE'RE DEVELOPING A SMALL
MOLECULE FOR INTERSTITIAL LUNG
DISEASE BROADLY, IT'S A PI-1
INHIBITOR, PLAZ MIDS
MIDINHIBITTOR 1 INHIBITORS AND
LISTENING TO DR. HOLTZMAN AND
OTHERS HERE TODAY THINKING ABOUT
SOME OF THE KEY MODELS WE REALLY
WANTED TO DEMONSTRATE THAT WE
HAD EFFICACY AND SORT OF THE
STANDARD OF CARE, GOLD STANDARD
MODEL AGAINST THE STANDARD OF
CARE AND SOME OF THE PRIOR
COMPOUNDS THAT HAVE BEEN
DEVELOPED AND TAKEN INTO THE
CLINIC, BUT NOT ADVANCED AND WE
THINK WE HAVE INSIGHTS INTO WHY
THOSE COMPOUNDS WERE NOT
SUCCESSFUL, ONCE THEY MOVED INTO
THE CLINIC AND IT HAS TO DO A
LOT WITH THE SCREEN AND WHETHER
THOSE COMPOUNDS WERE OR WERE NOT
BOUND WITH [INDISCERNIBLE].
SO WE FOCUSED ON INITIALLY
WITHIN SCLERODERMA AS THE
PRIMARY INDICATION BUT REALLY
AND I'LL SAY A -- WELL, 2 SIDES
OF THE SAME COIN LOOKING AT
INTERSTITIAL LUNG DISEASE, NOT
ONLY WITHIN THE SCLERODERMA
POPULATION BUT AS MANY OF YOU
WILL KNOW ON THE CALL THOSE
COMPOUNDS ARE BEING USED TO
TREAT IDIO PATHIC PULMONARY
FIBROSIS AND SO WE'VE GENERATED
QUITE A BIT OF DATA FROM THAT
STANDPOINT AS WELL AND THEN
INITIATED PHASE 1 HERE EARLIER
THIS YEAR AND WE'RE IN THE
PROCESS OF RUNNING THAT STUDY.
SO WE'VE COMBINED ABOUT, WELL
NOT ONLY OUR SEED BUT NIH
FUNDING AS WELL AS A SERIES
A-ROUTE TO ALTOGETHER ABOUT 13
AND HALF MILLION TO GET THE
PRODUCT THROUGH THE IND ENABLING
STUDIES AND INTO THE CLINIC AND
SO WE'RE FOCUSED REALLY IN ON
THAT STAGE OF THE DEVELOPMENT
PROCESS.
NEXT SLIDE, PLEASE.
AT LEAST FROM OUR STANDPOINT THE
FOUNDERS WORK WAS ALL BEING DONE
AT THE UNIVERSITY OF MICHIGAN,
PRIMARILY DR. DAN LAWRENCE AND
HIS LAB.
AND I HAPPEN TO BE INTRODUCED TO
HIM BACK IN LATE 2017 SO A LOT
OF THIS EARLY FOUNDATIONAL WORK
THAT HE HAD DONE WAS BEING
PULLED TOGETHER BUT IT REALLY
WASN'T ENOUGH TO BE ABLE TO TAKE
-- THERE WASN'T ENOUGH DATA TO
TAKE A STORY TO A VENTURE GROUP
OR EVEN PROBABLY EVEN SUPPORT A
LOT OF LATER STAGE NIH FUNDING.
AND SO WE NEEDED TO WALK VERY
SLOWLY, IF YOU WILL, AND RAISE
THE SMALL AMOUNT OF MONEY AND
FRIENDS AND FAMILY AS WELL AS
THE UNIVERSITY OF MICHIGAN
BIOMEDICAL VENTURES FUND TO HELP
US GET OFF THE GROUND AND START
TO DERISK THE ASSET AND THEN
THAT ENABLED US TO GO FOR A
COUPLE OF R43 SBIR GRANTS AND
THEN, THOSE DATA WERE SUFFICIENT
TO NOT ONLY DERISK THE ASSET
FURTHER BUT ATTRACT A VENTURE
ROUND OF FINANCING IN 22 OR LATE
FEBRUARY OF 2022.
AND THEN THOSE ARE THE FUNDS
THAT WE'VE BEEN CAPITALIZING ON
TO GET TO THE POINT THAT WE'RE
CURRENTLY AT AND WILL BE RAISING
ANOTHER ROUND HERE IN THE FIRST
HALF OF 2025 TO CONTINUE THE
DEVELOPMENT PROGRAM.
THE FIRST PHASE 1 OF THE SBIRs
ALLOWED THE COMPANY TO BRING
MYSELF ON AND A COLLEAGUE OF
MINE WHO'S HAD A LOT OF
EXPERIENCE IN PRECLINICAL
DEVELOPMENT AND WE WERE ABLE TO
GET SOME OF THE INITIAL GENE
TALKS DONE, ACTUALLY
DR. HOLTZMAN HAD A NICE SUMMARY
CHART THERE AND WE KIND OF
TICKED DOWN THROUGH ALL OF THOSE
IND ENABLING STUDIES AND EARLY
ASSESSMENT PROGRAMS IN ADDITION
TO IN PARALLELLING ON THE CMC
ACTIVITIES WHICH ARE QUITE
CRITICAL, AND WE HAD A GOOD TEAM
TO HELP US BE ABLE TO DO THAT
WORK.
AND THAT REALLY -- SO WITH THE
R43 FUNDS, THE FRIENDS AND
FAMILY FUNDING, WE WERE THEN
IEBL TO ALSO BRING ON A BROADER
TEAM WHERE WE HAD THE CMC
EXPERTISE, WE HAD THE CLINICAL
AND CLIN OPS AND REGULATORY
STRATEGY AND DNPK, AS WELL AS
PRODUCT MANAGEMENT SOY IT WAS A
GROUP OF INDIVIDUALS THAT HAD
WORKED TOGETHER BEFORE, COULD
ALL MOVE ASSETS THROUGHENTIOUS
FICIENTLY, ALMOST EVERYONE IN
THE GROUP HAD SOME APPROXIMATE
NOT ALL OF THEM HAD SOME LARGE
PHARMA EXPERIENCE AS WELL AS
TIME IN A VENTURE FUNDED
ACTIVITY.
SO, YOU HAD A LOT OF FOLKS THAT
UNDERSTOOD HOW TO MOVE THE
PROGRAM FORWARD ON A FAIRLY
CAPITAL EFFICIENT BASES.
NEXT SLIDE.
THANKS SO THIS AND THE NEXT
SLIDE ARE JUST 2 EXTRACTS IF YOU
WILL OF WAWE WERE FOCUSED ON IN
THE PHASE 1 FUNDING WHICH AS YOU
KNOW WAS A COUPLE HUNDRED
THOUSAND DOLLARS, SO IT'S ENOUGH
TO MAKE PROGRESS BUT NOT A LOT
OF PROGRESS AND THEN THE PHASE 2
AWARDS WE WERE FORTUNATE ENOUGH
TO GENERATE THE RIGHT KIND OF
DATA AND RESULTS IN PHASE 1,
DERISK THE PROGRAM, FURTHER AND
GENERATE DATA THAT ACTUALLY ALSO
WAS SUPPORTIVE OF THE SERIES A
FINANCING WHICH ALLOWED US TO
BRING ABOUT $9 MILLION IN, SO WE
HAD A COMBINATION OF AN R43 AND
44 GRANT IN THE NIIAMS DIVISION
AND REALLY FOCUSED IN ON
RHEUMATOLOGY WELL AS AS -- NEXT
SLIDE, PLEASE.
AS WELL AS NHLBI AND SO WE WERE
ABLE TO FIGURE OUT WHAT PIECES
OF THE TOTAL DEVELOPMENT PROGRAM
WARRANTED FUNDING THROUGH THESE
GRANT MECHANISMS AND ALL OF
WHICH WAS TIED TOGETHER WITH THE
AIM OF MOVING THE ASSET TOWARDS
COMPLETING SUCCESSFULLY THE IND
ENABLING ACTIVITIES, GETTING
FEEDBACK FROM FDA RELATIVELY
EARLY ON IN THE PROCESS, THROUGH
PREIND PACKAGE AND THEN FILING
AN IND IN MARCH, EARLIER OF THIS
YEAR, AND SO, FROM OUR
STANDPOINT OTHER THAN SORT OF
THE TIME DELAYS WHICH I THINK
DR. HOLTZMAN ALLUDED TO AS
YOU'RE GOING THROUGH THE GRANTS
AND YOU DON'T GET EVERY 1 OF
THEM AS ALL OF YOU KNOW,
AUTHORIZED FOR FUNDING ON
EXACTLY YOUR SCHEDULE, BUT
INDEED, THE DATA WERE EVENTUALLY
COMPELLING ENOUGH TO WOR RANT
THE FUNDING BOTH AT THE NIH
LEVEL AS WELL AS AT THE VENTURE
LEVEL CAPITAL AND WE WERE ABLE
TO MOVE FORWARD WITH A MAY
PROCEED AUTHORIZATION FROM FDA
AND WE'RE FOCUSED IN NOW ON
EXECUTING THAT FIRST PHASE OF
THE PHASE 1 PROGRAMS.
NEXT SLIDE, PLEASE.
SO DR. HOLTZMAN'S RIGHT,
[INDISCERNIBLE], GO THROUGH THE
LINES HERE BUT JUST TO GIVE YOU
AN IDEA OF SORT OF THE LEVEL OF
DETAIL THAT YOU TRY TRACKING
FROM, AND REALLY WORKING FROM
THE BACK END OF WHEN YOU HOPE TO
GET TO WHATEVER THAT PARTICULAR
MILESTONE IS, AND THEN YOU START
TO MOVE FORWARD TO THE PRIMARY
ACTIVITIES THAT HAVE TO GET
DONE, EARLY ON AND YOU CERTAINLY
START TO IDENTIFY WHERE YOUR
GAPS ARE AND I THINK 1 OF MY
CO-PRESENTERS HERE BEING SCIENCE
IS UNPREDICTABLE, WELL
DEVELOPMENT IS UNPREICTIBLE AS
WELL, AND WHO COULD HAVE
PREDICTED COVID INTERRUPTING THE
PATHWAY.
SO TRYING TO WORK THROUGH A
PANDEMIC, GLOBAL PANDEMIC ALONG
WITH KEEPING THE PROGRAM
ON-TIME, FINDING A WAY TO GET
INTO THE CUE FOR VARIOUS,
COMPLETION OF THE VARIOUS IND
ENABLING STUDIES HAVING TO
SWITCH THE SECOND NONRODENT
SPECIES TO NONHUMAN PRIMATES TO
GINNY PIGGINGS AS COVID DEMANDS
ON NHP AVAILABILITY AND
UTILIZATION WERE DRIVING THE
PRICE UP ABOUT 5 OR 6 TIMES, IF
YOU COULD EVEN FIND YOUR WAY
INTO A CRO QFOR THAT SPECIES.
A LOT OF PIECES KEEP MOVING
FORWARD AND SO, AS SIMPLISTIC AS
THE CHART IS, IT DOES HELP YOU
KEEP EVERYONE ON TRACK AND KEEP
YOU FOCUSED IN ON WHEN WHERE THE
KEY GAPS ARE AND WHEN YOUR
TIMELINES ARE GOING TO BE MET
DOWN THE ROAD.
NEXT SLIDE.
YEAH, SO THIS IS JUST SORT OF
THE EMERGING PROFILE, IT'S
REALLY JUST A SUMMARY OF WHERE
WE ARE RIGHT NOW.
SO, I THINK AS I JOINED THIS
SESSION HERE WITH DR. HOLTZMAN,
HE HIGHLIGHTED A LOT OF THESE AS
HAVING VERY CLEAR TARGET, CLEAR
IN OUR CASE INHIBITION ACTIVITY
BEING ABLE TO SEE ENGAGEMENT,
NOT ONLY IN THE PRIMARY ANIMAL
MODELS FOR EFFICACY AS WELL AS
SAFETY, BUT ALSO IN THE EARLY
STAGES OF PHASE 1 AND WE'VE GOT
A FAIRLY HIGH THRESHOLD OF TOP
DOZE THAT WILL BE EVALUATED
RELATIVE TO WHAT WE THINK THE
EXPOSURE REQUIRED FOR EFFICACY
WILL BE, SO, OBVIOUSLY ONCE WE
UNBLIND THE STUDY AND SEE WHAT
THOSE DATA ACTUALLY LOOK LIKE,
WE WILL KNOW HOW CLOSE WE WERE
TO BEING ON TRACK BUT WE THINK
WE HAVE A PRETTY GOOD MARNLIN TO
EVALUATE.
AND THEN IN OUR CASE, SINCE
HAVING PATIENTS THAT ARE NULL
FOR P A I 1 HAVE BEEN ASSOCIATE
WIDE BLEEDING DISORDERS EVEN
THOUGH WE'RE NOT DEVELOPING A
COMPOUND THAT ACTUALLY KNOCKS
OUT ALL P A I ACTIVITY, WE'RE
MORE OF A CHARACTERIZED AS A
RESTAT LIKE EFFECT WHERE YOU
RETURN DYSFUNCTIONAL LEVELS OF P
A I 1 DOWN TO NORMAL LEVELS BUT
EVERYONE ALWAYS ASKS YOU FOR
DATA ABOUT BLEEDING RISK AND SO
WE'VE HAD TO CONSTANTLY GENERATE
THAT NOT ONLY IN VIVO BUT EXVIVO
AND CONTINUE TO LOOK AT THAT.
IT'S NOT ACTUALLY INTERESTINGLY
ENOUGH AN ISSUE FROM THE FDA
STANDPOINT THAT HAS BEEN A
CONCERN AS WE'VE GONE THROUGH
THE INITIAL IND SUBMISSION, BUT
IT IS A CONSTANT QUESTION FROM
ALL OF THOSE POTENTIAL STRATEGIC
PARTNERS DOWN THE ROAD THAT AS
DR. LIU MENTIONED, YOU WILL
DEFINITELY NEED AS YOU ADVANCE
THE COMPOUND INTO LATER STAGES.
NEXT SLIDE.
OKAY, SO, SUMMARY, ALSO MY YOB
CORPS IS BEING THE LAST
PRESENTER IS TO GIVE THE GIFT OF
TIME TO THE MODERATORS WHO ARE
GOING TO CONVENE THE PANEL
AFTERWARDS AND JUST SUMMARIZE.
SO WE WERE ABLE TO REALLY PARLAY
THE FIRST 4 AND HALF MILLION, 4
OF WHICH WAS NIH PROVIDED
THROUGH R43 AND R44 GRANTS TO
GENERATE THE KIND OF DATA THAT
WOULD BE NEEDED NOT ONLY TO
RERISK THE ASSET FROM AN
INVESTOR STAND POINT WHICH WAS
HELPFUL IN ATTRACTING OUR SERIES
8 INITIAL ROUND OF FINANCING BUT
ALSO BEING ABLE TO DELIVER THE
IND PACKAGE THAT WAS SUFFICIENT
FOR FDA ABNORMAL GLUCOSE
TOLERANCE RISATION TO ADVANCE
THE PROGRAM.
SO COMING OUT OF COMPLETION HERE
OF THE PHASE 1 A AND 1 B ARE THE
SAD AND MAD FACES OF THE EARLY
CLINICAL STUDIES AND HEALTHY
VOLUNTEERS, WE'LL BE LOOKING AT
A PHASE 2A PROGRAM IN PATIENTS
OVER ABOUT A 6 MONTH PERIOD OF
TIME GENERATING THE DATA THAT
CAN DERISK THE ASSET TOWARD THE
NEXT ROUND OF INVESTMENT.
ALL RIGHT.
SO I THINK THAT'S IT FOR MY
PRESENTATION.
AND HAPPY TO ANSWER QUESTIONS AS
WE GO THROUGH THE PANEL
DISCUSSION.
>> YEAH, I THINK WE WILL DO THE
QUESTIONS DURING THE PANEL
DISCUSSION.
THAT'S GREAT.
>> THANK YOU.
>> THANK YOU DR. BENOIT,
HONORARY DOCTOR.
APPRECIATE THAT.
IT WILL GET ME A PAID DINNER
TONIGHT.
[LAUGHTER]
>> SO I THINK THAT THE ORDER
THAT THEY HAVE US GOING IN IS ME
AND THEN JAMES, I WAS GOING TO
GO VERY BRIEF, MUCH EARLIER IN
AND IT'S LETTING ME DO MY KRID
VIDEO BUT THAT'S FINE, YOU DON'T
NEED TO SEE ME, ANYWAY IT'LL
PROBABLY BE BETTER FOR -- THERE
WE GO.
IT MAY ACTUALLY BE BETTER TO
JUST HAVE IT OFF.
WE WILL SEE HOW STABLE IT IS.
SO THIS IS JAMES' IT WE CAN LOAD
THE 1 THAT SAYS THE AUDIO ON THE
END OF IT, PLEASE.
SO YOU'RE GETTING A PREVIEW OF
JAMES THERE.
JAMES DO YOU MIND JUMPING IN?
>> MY PLEASURE.
>> THANK YOU SO MUCH, LET'S PUT
JAMES UP AND WE WILL FIND
DR. ZIADY'S.
>> SAME THING, BACKWARDS FAST.
ALL RIGHT, SO, THE TALK I'M
GOING TO GIVE IS I WOULD SAY A
BRIEF THING, IS I THOUGHT IT
WOULD BE ENTERTAINING TO SEE A
LOT OF CONCEPTS THESE GUYS
TALKED ABOUT BUT, FOR A PROJECT
THAT HAD PROBLEMS.
I'VE GOT A LOT OF PROJECTS BUT I
THOUGHT THIS 1 HAD MORE
EDUCATIONAL CONTENT.
NEXT SLIDE.
SO, THE DISCLOSURES SORT OF
START OFF SO NHLBI FUNDED PART
OF THIS BUT THERE'S 4 DEFINITE
COMPANIES LISTED HERE, HERE ON
GSK'S LUNG DECS DIVISION,
[INDISCERNIBLE] AND ALL 4 OF
THOSE HAVE NO LONGER EXIST,
AFTER HELPING ME WITH THIS
PROJECT SO FAR NHLBI HAS
SURVIVED COLLABORATING WITH ME
BUT WE'LL SEE.
NEXT SLIDE.
SO THIS ISN'T EXACTLY EVERYBODY
ELSE PUT IT BUT CLOSE ENOUGH,
THERE'S A BUNCH OF THINGS YOU
WANT FOR YOUR IDEAL TARGET
PROFILE EMPLOY YOU WANT TO
TARGET THE MOLECULAR DRIVERS OF
DEC, YOU WANT LIMITED OFFTARGET
CENTER FOR EXCELLENCE ON AGINGS,
YOU WANT A THEREFOREY METHOD
THAT'S VIABLE AND YOU WANT THE
WHOLE THING TO BE VIABLE AND
REASONABLE TO MAKE PROTECTIVE
IP.
NEXT SLIDE.
SO 1 OF THE DECS I STUDY,
PULMONARY ARTERIAL HYPERTENSION,
IT'S A NICE TARGET, THERE'S A
PATHWAY ACE 2 WHICH LOOKS LIKE
IT HITS ALL OF THE BMPR2 DOWN
STREAM OW YOU MIGHT IMAGINE IF
BMPR2 IS PENETRATED YOU COULD
TREAT PATES WITH ACE 2.
NEXT SLIDE.
SO THERE'S A SMALL COMPANY
CALLED APIRON OUT OF GERMANY OR
AUSTRIA THAT HAD PATENTS ON
THEM, WE GOT TO GIVE THEM TO
MUTATIONS IN MICE, AND THEY
WORKED GREAT IN OUR HANDS, SOME
OTHER GROUPS TRIED IT IN OTHER
MODELS, OF PULL MONITORRORY
HYPERTENSION, IT WORKED GREAT
THERE, PRECLINICAL DATA IN MOST
MODELS BUT IT DID GRIT FOR
PULMONARY HYPERTENSION, SO THEY
SOLD THIS FOR GREAT PILES OF
MONEY.
SO SO FAR THIS LOOKS GREAT.
LOOKS LIKE IT SHOULD BE HITTING
THE FOUNDATION OF THE DISEASE,
LIMITED OFF TARGET EFFECTS
BECAUSE THE H2 IS FAIRLY ALREADY
A BIOLOGICAL PRODUCT AND IT'S
WELL KNOWN WHAT IT DID AND IT'S
GOT PREDICTABLE IP.
SO GSK GETS BACK AHOLD OF ME AND
WANTS A FIRST IN MAN TRIAL OF
ACE 2 IN MEL MONITORARY
HYPERTENSION AND WE DID IT AND
WE PUBLISH IT, IT LOOKS GREAT.
NEXT SLIDE.
THE -- I'M NOT GOING TO SHOW ALL
THIS STUFF BUT THE CLINICAL END
POINTS WERE WONDERFUL, IT
DROPPED THE PULMONARY PRESSURES,
HIT ALL THE RIGHT MOLECULAREND
POINTS.
THE HUMAN TRIALS, THE HUMAN CLIN
TRIALS LOOK LIKE, IT LOOKS SAFE.
NEXT SLIDE EMPLOY BUT IT'S
ACTUALLY TERRIBLE, IT'S TERRIBLE
BECAUSE THE ACTUAL DRUG, FIRST
OFF IT'S A SHORT HALF LIFE AND
REQUIRES DIRECT IV
ADMINISTRATION AND SO YOU CAN
WORK AROUND THAT BUT THAT'S A
HARD DRUG TO COMMERCIALIZE.
BUT SECONDLY EVEN GSK HAD
DIFFICULTY MAKE THANKSGIVING
THING, THE FUNCTIONAL
REQUIREMENTS MAKE POST
TRANSLATIONAL MODIIVESS, IT CAN
BE ONLY MADE IN MAMMALIAN CELLS,
IT WAS INSANELY DIFFICULT TO
MAKE, AND GSK BARELY HAD ENOUGH
FOR EVEN A SMALL TRIAL.
NEXT SLIDE.
HOWEVER, NO PROBLEM, RIGHT?
WE KNOW HOW THIS PATHWAY WORKS
WE KNOW HOW IT WORKS IS WAS LIKE
3000 PAPERS THAT SAY THIS, IS H2
CONVERTS TO [INDISCERNIBLE], AND
MASS 1 AND IT'S' 7 PEPTIDE,
SHOULD BE SUPER EASY TO MAKE,
IT'S ALWAYS UNSTABLE BUT GSK HAS
TONS OF PROPRIETARY TECHNOLOGIES
TO STABILIZE IT.
NEXT SLIDE.
GLAKS O DOES THAT AND THEY GIVE
US THE DRUG AND IT DOESN'T WORK.
WE TRY IT IN THE SAME MOUSE
MODELS AND IT DOESN'T DO WHAT
ACE 2 DID.
AND I WORRY THAT THE STUFF THEY
MODIFIED TO STABILIZE IT MADE IT
NO LONGER HIT THE RECEPTOR BUT
IT DOESN'T MATTER BECAUSE GSK
SHUT DOWN THEIR LUNG DISEASES
DIVISION, NOT RELATED TO THIS
AND THEY GAVE THE PATENT BACK TO
APIRON.
NEXT SLIDE.
SO APIRON, THE GUIDES THAT DID
APPEARON MADE A NEW COMPANY
CALLED ALTEROUS, AND INSTEAD OF
MAKING A -- TRYING TO STABILIZE
ANG 1-7, AND BY BLOCKING THESE
PROTEIN COMPLEX YAIG YAISS YOU
CAN MAKE IT GO WAY UP.
THIS IS JUST A FIGURE SHOWING
THAT ACE 2 BRINGS ANG 1-7 UP AS
A RELATOR IN BLOOD AND THE
COMBINATION OF THEIR DRUG IMETS
US UP TO 460 EMPLOY SO WE CAN
REPRODUCE THE THING WITH SMALL
MOLECULE INHIBITORS.
NEXT SLIDE.
NEXT SLIDE AND IT STILL DOESN'T
WORK.
IN FACT WHEN WE INCREASE THE
DOSE TO GIVE IT EVEN MORE ANG
1-7 THE PULMONARY HYPERTENSION
GETS WORSE.
NEXT SLIDE.
AND OH, ALTASD E R-- ALTERRAS
WENT OUT OF BUSINESS.
MAYBE HOW ACE 2 IS WORKING HAS
NOTHING TO DO WITH THIS.
NEXT SLIDE.
SO AT THIS POINT WHAT LOOKED
GOOD TO BEGIN WITH NOW LOOKS
LIKE A DISASTER.
WE DON'T HAVE A DELIVERY METHOD,
WE CAN'T MAKE IT A REASONABLE
PRICE, WE'RE NOT EVEN SURE WE
HAVE THE RIGHT TARGET.
KEEP GOING.
BUT WE KNOCKED OUT THE MASS
RECEPTOR IN MICE AND WHEN YOU
KNOCK OUT THE MASS RECEPTOR IN
MICE, ACE 2 NO LONGER WORKS SO
MASS IS THE RIGHT RECEPTOR.
NEXT SLIDE.
MOST MASS RECEPTOR AGONISTS THAT
ARE OUT THERE AREN'T ACTUALLY
MASS RECEPTOR AGONISTS BUT
THERE'S A COMPANY CALLED ARENA
PHARMACEUTICALS THAT HAD A
CLEVER CHEMIST THAT DID TONS OF
NICE WORK AND FOUND AN ACTUAL
MASS RECEPTOR AGONIST AND IT
WORKED GREAT, JUST AS WELL AS
ACE 2.
NEXT SLIDE.
BUT THEY WENT OUT OF BUSINESS.
[LAUGHTER]
AND THEIR PATENT WAS BOUGHT BY
PFIZER WHICH IS ABOUT WHERE WE
STOP NOW .
NEXT SLIDE.
SO GOOD NEWS IS THAT IT ALL
LOOKS PRETTY GOOD, TARGET
PROFILEETS MOLECULAR DRIVERS OF
DISEASE, LIMITED OFF TARGET
EFFECTS, THEREFOREY METHODS
VIABLE, IT'S SMALL MOLECULE,
THAT'S EXTREMELY STABLE AND
SUBCUTANEOUS, REASONABLE PRICE
TO MAKE, SMALL MOLECULE DRUG,
PROTECTABLE IP, AND THERE
EXISTING PATENTS ON THE THING.
NEXT SLIDE.
[LAUGHTER]
AND SO, THE LAST PROBLEM YOU
HAVE IS IF THE IP OWNER IS
INTERESTED IN THE INDICATION O
I'M GOING TO SEE IF I CAN'T GET
AHOLD WITH PFIZER AND SEE IF
THEY'RE INTERESTED IN PURSUING
THE PROJECT AND THE REASON FOR
THAT IS, IT'S LOVELY AND WOULD
GIVE ME A NICE PARTNER TO
PROCEED BUT IF NOT THERE'S A FEW
PROBLEMS WITH THE DRUG, IT'S A
GREAT DRUG BUT IT COULD BE MADE
MORE SOLUBLE FOR FEW THINGS TO
IMPROVE IT AND IF PFIZER'S NOT
INTERESTED, WE WILL REENGINEER
AND PROCEED FROM THERE.
NEXT SLIDE.
SOPHISTICATED REALLY A KEY TAKE
AWAY HERE IS THAT ACHIEVING A
TARGET PROFILE, SOMETIMES IT MAY
LOOK GOOD IN THE BEGINNING BUT
IT SOMETIMES REQUIRING WORKING
EITHER BECAUSE THE ORIGINAL
DIRECT PATHWAY YOU'RE USING JUST
TURNS OUT NOT TO BE VIABLE OR
BECAUSE IT TURNS OUT WHAT THE
LITERATURE ACCEPTS AS TRUE ISN'T
WHEN YOU START LOOKING AT IT OR
ANY OTHER VARIETY OF REASON WHY
YOU COULD HAVE TROUBLE SELLING
THIS.
ONE THINK THIS I WON'T TALK A
LOT ABOUT IS GETTING FUNDING FOR
THIS AND THERE'S A LOT OF
DIFFERENT FUNDING SOURCES FOR
THIS.
NHLBI PAID FOR THIS WITH RO-1S
AND PROJECT GRANTS.
WE HAD SMALL BUSINESS
COLLABORATIONS WITH THE
VENTUREICALTAL AND SMALL
BUSINESS GRANTS, IS SBIRS AND
STTRS, SO THERE'S A LOT OF WAYS
CAN YOU PAY FOR THIS SORT OF
THING.
I GUESS WHAT I'M SAYING IS IS
THAT MY EXPERIENCE IN THIS
PROJECT THAT HAS HAD A LOT OF
LUMPS IN IT, IS THAT IT REALLY
IS A CONFIRMATION ANECDOTALLY OF
ALL THE OTHER STUFF THE GUYS
HAVE TALKED ABOUT.
AND I THINK THAT'S EVERYTHING I
HAVE TO SAY.
IF I MY CO MODERATOR IS READY?
>> YEAH, I THINK THEY HAVE IT.
LET'S SEE.
AND I WANTED TO LOOK THEA THE
HURDLES, AND JAMES AS WELL AS WE
ARE AND OTHER SPEAKERS ON THE
PANEL AND DR. HOLTZMAN AND
DR. BENOIT, THAT YOU KNOW IN
DEVELOPMENT AND DEFINING THE
TARGET PRODUCTS AND GETTING THEM
TO MARKET, WE ARE STILL SORT OF
AN EARLY STAGES OF TRYING TO GET
A FEW PRODUCTS TO MARKET, 1 OF
THEM'S GENE THERAPY WHICH I
WON'T TALK ABOUT TODAY AND THE
OTHER IS A LAB TEST FOR
BIOMARKERS OF DISEASE, WHICH IS
TURNING INTO AN INTERESTING
PROJECT BUT I WANTED TO FOCUS
ON, YOU HEARD A LOT TODAY ABOUT
-- COULD I HAVE THE NEXT SLIDE
-- I WANT TO FOCUS ON THE
HURDLES BECAUSE YOU HEARD A LOT
ABOUT -- THESE ARE MY
DISCLOSURES HERE.
THIS IS OTHER PROJECTS HAVE BEEN
FUNDED IN THE LAB BY THE NHLBI
AND CF FOUNDATION.
WE RECENTLY GOT AN SBIR GRANT
ASK WE'VE GOTTEN SBIR FUNDING
BEFORE FOR THE GENE THERAPY WORK
THAT WORK ON TODAY WAS SUPPORTED
BY CATALYZE SO THE PROGRAM THAT
MIKE AND LAURA SPOKE ABOUT
EARLIER, FANTASTIC PROGRAM AND
SOMETHING THAT IN MY OPINION
EVERYONE WHO WANTS TO INNOVATE
AND REALLY SORT OF REDUCE TO
PRACTICE WHAT THEY'RE DOING, AND
THEN NOT JUST HAVE VISION BUT
TURN IT INTO SOMETHING SHOULD
REALLY INTERACT AND CROSS PATHS
WITH THIS PROGRAM AT THE NIH
IT'S REALLY AMAZING.
WE'RE WORKING WITH A COMPANY
CALLED GENEXYS, JUST TO DISCLOSE
THAT AND I'M AN INVENTOR ON A
NUMBER OF PATENTS I WILL DISCUSS
TODAY.
SO NEXT SLIDE PLEASE.
I REALLY WANT TO FOCUS ON THE
CHALLENGES.
YOU HEARD A LOT ABOUT BALANCING
VISION AND FEASIBILITY.
I THINK THAT'S IMPORTANTOT
SCIENTIFIC LEVEL, VISION IS NOT
IN SHORT SUPPLY, SO I THINK
GENERALLY, YOU DON'T GO INTO
SCIENCE IF YOU'RE NOT A
VISIONARY KIND OF PERSON THAT
YOU KNOW WANTED TO WIN THE NOBEL
FOR CURING ALL DISEASE AT SOME
POINT.
I THINK THAT THAT'S THE WAY A
LOT OF PEOPLE WHO DO BASIC
SCIENCE OR TRANSLATIONAL SCIENCE
ARE BUILT TO BEGIN WITH.
SO VISION IS, I DON'T THINK IN A
LOT OF SHORT SUPPLY BUT YOU
REALLY ARE TO COUPLE THAT WITH
FEASIBILITY AND THAT REALLY IS
THE -- QUITE IMPORTANT.
YOU HEARD QUITE A BIT ABOUT THAT
TODAY, AND YOU HAVE TO MAKE SURE
YOU CAN SCALE UP WHATEVER YOU'RE
MAKING, YOU ARE DOING, IF YOU'RE
MAKING A PRODUCT LIKE A SMALL
MOLECULE OR A GENE THERAPY
VECTOR, HAS TO BE SCALABLE, HAS
TO BE REPRODUCIBLY MADE, HAS TO
BE TABLE, YOU CAN STORE IT, A
LOT OF THINGS GO INTO, YOU KNOW
DEFINING THE PRODUCT ISSUES THE
TARGET PRODUCT, PART OF WHAT
GOES INTO DEFINING THAT IS CAN
YOU ACTUALLY MAKE SOMETHING THAT
WILL END UP BEING A PRODUCT
THAT'S VIABLE AND NOT JUST
SOMETHING THAT AFFECTS A PATHWAY
IN A CELL LINE IN A SINGLE
EXPERIMENT.
IT HAS TO BE SOMETHING THAT CAN
BE KEPT, YOU KNOW ON THE SHELF
IN A BOTTLE OR PILL AND
DELIVERED AND WORK STABLY AND
NOT BE TOXIC.
THERE'S A LOST THINGS THAT CAN
INFORM SELECT, YOU KNOW DEFINING
THE TARGET PRODUCT.
SO I THINK YOU HEARD A LOT ABOUT
THASHES I WANTED TO SORT OF
TOUCH A LITTLE BIT ON SOME OF
THE SHORT COMINGS, OR
LIMITATIONS THAT YOU RUN INTO,
FOR US ESPECIALLY, YOU KNOW
ACADEMIA, WHILE A LOT OF THESE
INNOVATIVE IDEAS DO SORT OF
PERKULATE IN ACADEMIA, HISTORY
OF ACADEMICS INTERACTING WITH
SPIN-OFFS OR COLLABORATING WITH
INDUSTRY AND COMING UP WITH
AMAZING THERAPIES, AND A LOST
THE GREAT THERAPIES OUT THERE
RIGHT NOW FOR CF, WHICH IS 1
THING WE WILL TALK ABOUT TODAY,
1 OF THE GREATEST THERAPIES THAT
HAVE BEEN THE MODULATORS
BASICALLY WERE DEVELOPED USING
BASIC SCIENCE ASSAYS LIKE
[INDISCERNIBLE] CHAMBER
MEASUREMENTS AND CHLORIDE
FUNCTION TESTS FOR ACTIVATION OF
THE CHANNELS FOR SMALL
MOLECULES.
SO BASIC SCIENCE PLAYED A BIG
ROLE BUT ACADEMIC SETTINGS,
FIRST OF ALL HAVE SOME SHORT
COMINGS.
ONE IS THERE'S MORE OF A PUSH TO
INVENTION RATHER THAN A PULL IN
RESPONSE TO A PREDEFINED
VALIDATED USER NEED, SO, I THINK
YOU HEARD THAT IN A COUPLE OF
TALKS TODAY, THAT HAVING A VERY
DEFINED NEED AND AN IMPORTANT
MARKET SPACE, AND THAT HAS A
DESCENT MARKET SHARE, SO THAT
INVESTORS WILL BE INTERESTED IN
INVESTING IN IT, THAT CAN BE
PROTECTED, IS AN IMPORTANT PART
OF DESIGNING YOUR TARGET
PRODUCT.
I THINK IT'S -- YOU REALLY HAVE
TO THINK ABOUT A LOT ABOUT
FORMALIZING THE ENVIRONMENTS OF
DEFINING THE PRODUCT IN A FORMAL
WAY EMPLOY THAT'S PROBABLY WHERE
SOME OF THE FRICTION OCCURS IN
ACADEMIA, THE WAYS THAT WE ARE
TRAINED AND THINK ABOUT DEFINING
EXPERIMENTS AND CONTROLS, ARE
IMPORTANT AND NECESSARY, BUT
THERE'S ALSO STANDARD OPERATING
PROCEDURES THAT CAN BE VERY
DETAILED AND HAVE TO BE VERY
MODULAR SO THAT THEY CAN BE
EASILY CARRIED OUT IN DIFFERENT
LABORATORIES AND DIFFERENT
SETTINGS AND THERE'S NOT SORT OF
CENTER CENTER FOR EXCELLENCE ON
AGINGS AND WHAT HAVE YOU THAT
HAPPENS IN ACADEMICS AND
RESEARCH HAVE TO BE CONSIDERED
AND REALLY QUITE A LOT OF TIME
AND MONEY TO SORT OF NAIL DOWN.
I THINK ALSO FROM THE VERY EARLY
POINT AND YOU'VE HEARD A BUNCH
OF TALKS ABOUT THIS TODAY AS
WELL, YOU HAVE TO THINK ABOUT
REGULATORY AND REIMBURSEMENT
CONSIDERATIONS, AND IN DESIGNING
OR DEFINING YOUR TARGET
PRODUCTS, EVEN THOUGH, YOU KNOW
YOU HAVE A SCIENTIFIC QUESTION
AND SCIENTIFIC PROBLEM, YOU'RE
TRYING TO SOLVE LIKE JAMES JUST
SHOWED, YOU REALLY WANT TO BE
THINKING ABOUT WHAT THE
REGULATORY AND THE REIMBURSEMENT
LOOKS FOR THAT, LOOKS LIKE FOR
THAT, VERY EARLY ON WHICH IS
SOMETHING WE'RE NOT TRAINED TO
DO AND SO, -- SO YOU SORT OF
HAVE TO THINK BACKWARDS FROM HOW
SAFE WILL THIS BE?
WHAT KIND OF REIMBURSEMENT WILL
THERE BE?
WHAT KIND OF COVERAGE?
, THENEY NEED AND SAFETY PROFILE
OF THIS, SORT OF YOU START THERE
AND WORK YOURSELF BACK TO WHAT
THE PRODUCT IS GOING TO BE.
IF YOU START WITH SOMETHING THAT
MISSES THESE CONSIDERATIONS, YOU
CAN SORT OF CATCH UP ON THEM
LATER ON BUT YOU COULD RUN INTO
TROUBLE WHERE YOU COULD FIND
YOURSELF FAR OFF THE MARK AND
THEN YOUR PRODUCT SORT OF FAILS,
NEXT SLIDE, PLEASE.
IT'S REALLY THESE 2 SLIDES ON
THE TRANSFORMATIONS, THE
TRANSFORMATIONS FOR US THE
BIGGEST CHALLENGES HAVE BEEN
INSTITUTIONAL 1S, SORT OF IN THE
ROOM AT LEAST FOR US IS THAT
INSTITUTIONS AND ACADEMIC
INSTITUTIONSENTIOUS SPECIALLY
ARE NOT BUILT TO TAKE HIGH RISK.
YOU KNOW INCREMENTAL MOTIVATION
IS REWARDED BECAUSE THAT'S WHERE
THE FUNDING AS BEEN GEARED OVER
THE LAST 30 YEAR ANDS THAT'S
CHANGING IN THE DISCUSSIONS WITH
MARA, AND CHANGES WILL NOT BE
WILL ONLY THINGS THAT ARE
CONSIDERED FOR THESE BREAD AND
BUTTER GRANTS AND RO-1 GRANTS
WHICH ARE TYPICALLY NOT THAT
RISKY AND SO THE BETTER THE
RANKING OF AN INSTITUTION, THE
YOU KNOW THAT THERE IS A
LIKELIHOOD THAT THAT INSTITUTION
WILL NOT BE THE BEST PLACE TO
INNOVATE AND NOT BE THE BEST
PLACE TO SUPPORT INNOVATION AND
I'M TALKING ABOUT INSTITUTIONAL
SUPPORT SO I'M TALKING ABOUT
THINGS LIKE SUPPORT WITHIN
DIVISIONS AND DEPARTMENTS IN
TERMS OF YOU KNOW SEED FUNDING,
START UP FUNDING AND INTERNAL
FUNDING WHICH CAN HELP A LOT
ESPECIALLY WHEN YOU GET AN IDEA
HERE OR THERE WHETHER THE SEED
FUNDING AND WHICH IS USUALLY
AVAILABLE AT THE INCREMENTAL
FOLKS SO THEY BRING IN MORE
GRANTS OR WHETHER YOU CAN GO FOR
MOVING TECHNOLOGY AND A LOT OF
TIMES THAT'S A CHALLENGE, AND
SO, ANOTHER THING IS IDENTIFYING
TARGET.
I THINK PEOPLE DON'T THINK ABOUT
THAT ENOUGH, AND YOU HAVE TO
THINK ABOUT IT EARLY ON AND IF
YOU DON'T HAVE A PARTNER THAT
WILL HELP YOU COMMERCIALIZE A
PRODUCT, NO MATTER WHAT THE
TARGET OF YOUR PRODUCT, IF IT'S
NOT SOMETHING COMMERCIALIZATION
PARTNERS ARE NOT INTERESTED IN,
AND I THINK YOU HAVE TO BE
REALLY GOOD AT INTERDISCIPLINARY
COORDINATION SO YOU WILL HAVE TO
WORK TOGETHER WITH RESEARCH AND
DEVELOPMENT FOLKS, YOU HAVE TO
THINK ABOUT MARKETING, YOU HAVE
TO THINK ABOUT MANUFACTURING AND
SCALE UP, YOU HAVE TO THINK
ABOUT PRIORITIES ALIGNING AND
YOU KNOW THAT'S COMPLEX TO DO.
AND SO IN MY OPINION, AND I
THINK MOST INVENTORS AND START
UP FOLKS ON HERE WOULD AGREE
THAT A LOT OF SUCCESS OF THESE
TECHNOLOGIES AND PICKING THE
RIGHT TARGET DOES HINGE ON A
SAVVY INVENTOR AND YOU HAVE TO
BE -- SUCCESS IS VERY SAVVY
INVENTOR-DEPENDENT WHICH I THINK
MISSES A LOT OF OPPORTUNITIES SO
THERE'S A LOT OF TIEWPTS THAT
ARE MISSED I THINK FOR PEOPLE
THAT AREN'T SAVVY THAT CAN'T
DEAL WITH THE POLITICS, THAT
CAN'T DEAL WITH THE MACHINATIONS
OF ACADEMIA AND WHAT IT REWARDS.
AND I THINK A LOT OF REALLY GOOD
IDEAS DO SORT OF FALL BY THE WAY
SIDE BECAUSE THEY'RE NOT SORT OF
-- THEY DON'T HAVE CHAMPIONS IN
PLACES WHERE INNOVATION IS SORT
OF TOUTED AS SOMETHING PEOPLE
ARE INTERESTED IN BUT REALLY
ACADEMICALLY SPEAKS THESE
INSTITUTIONS ARE NOT THAT
HEAVILY INVESTED.
NOW THERE ARE EXCEPTIONS TO
THAT, YOU KNOW I USED TO WORK AT
EMORY AND EMORY IS A PLACE THAT
YOU KNOW CAME UP WITH THE
REPLACEMENT FOR AZT AND THEY SAW
WHAT MOVING THE NEEDLE COULD
REALLY BE, AND SO, YOU KNOW THAT
WAS -- THAT WAS A PLACE WHERE
INNOVATION WAS REALLY HEAVILY
SUPPORTED.
WE WILL GO TO THE NEXT SLIDE.
SO A COUPLE TRY TO MOVE A LITTLE
FASTER HERE TO START THE PANEL
DISCUSSION, BUT TELL YOU ABOUT
THE BIOMARKERS WE'RE WORKING ON.
NEXT SLIDE, PLEASE.
SO THIS IS AN ATTEMPT TO TROY TO
GET AT THE [INDISCERNIBLE]
INDUSTRY IN CF LUNG DECLINE, SO
IN CF YOU HAVE THIS YEEN THAT
LEADS TO THE LUNG DISEASE, AND
IF YOU GO TO NEXT CLICK, PLEASE.
NEXT.
SO THIS IS AN EXAMPLE OF WHAT A
PATIENT LOOKS LIKE AND YOU CAN
SEE THAT THERE FEV1 LUNG
FUNCTION IS BECOMING MORE
ERRATIC WITH TIME AND IT'S HARD
TO PREDICT THAT WHEN YOU DON'T
KNOW WHAT THE REST OF THE
TRACINGS LOOK LEAK AND SO, NEXT
SLIDE, PLEASE, SO PRESENTLY USED
BIOMARKERS, NEXT.
I DIDN'T REALIZE THIS HAD SO
MANY -- ARE ALL LAGGING
INDICATORS AND WILL TELL YOU
ONCE IT'S BEEN ESTABLISHED SO
IT'S DIFFICULT TO REVERSE.
SO NEXT SLIDE.
AND THERE'S GOOD EVIDENCE THAT
THERE CONTINUES TO BE LUNG
FUNCTION DEDEADLINE SO THE
LIGHTER TRACE THAT'S ON TOP
THERE, THE GRAY TRACE IS SORT
OF, YOU CAN SEE LUNG FUNCTION
DECLINE THERE AND TRAJECTORY
LOOKS THE SAME AS NONTREATED
FOLKS IN THE BLACK TRACING,
EXACERBATIONS ARE DOWN BUT HIGH
EFFICACY MODULATORS, LUNG
FUNCTION DELINES IN CF AND
THAT'S FOR PEOPLE WHO CAN
TOLERATE THESE NEW MODULATORS.
SO THERE'S A NEED TO TRY TO --
THERE'S GOOD EVIDENCE THAT IF
YOU IMPROVE, -- IF YOU DO MORE
MONITORING FOR FOLKS, ON THE
LEFT-HAND SIDE HERE, CAN YOU SEE
THE IMPROVEMENT IN FEV1 SCORES.
IF YOU MONITOR PEOPLE WITHIN 28
DAYS, REPEAT VISITS RATHER THAN
THE 3 MONTHS REPEAT VISITS, IF
THEY FALL A CERTAIN PERCENTAGE,
IF YOU SEE THEM ONCE OVERALL
STRATEGY 4 WEEKS YOU THIS IS THE
IMPROVEMENT YOU CAN GET OF
CONVENTIONAL THERAPY OF CF
WITHOUT MODULATED THERAPY.
NEXT, PLEASE.
I THINK WE CAN ANY TO THE NEXT
1.
WHAT WE DEVELOPED IN THE LAB WAS
TO USE A HIGH THROUGH PUT
PROCEED I DON'T MEANIC APPROACH,
WHICH LOOKED AT 10S OF THOUSANDS
OF PROTEINS AND ACTUALLY FOUND
ABOUT 1100 PROTEINS THAT WERE
DEFINITE IN THE BLOOD THAT CAN
PREDICT WHAT HAPPENS WITH LUNG
FUNCTION.
COMPLEX, LUNG FUNCTION IS NOT 1
OF THESE THINGS WHERE YOU HAVE 1
MARKER THAT TELLS WHAT YOU'S
GOING ON WITH IT AND SO IF YOU
GO TO THE NEXT SLIDE, PLEASE.
THIS MAX SPEC DATA GENERATED
BASICALLY 474 MARKERS WHICH IS
WE CAN ONLY DO MY MASS SPEC
BECAUSE YOU CAN'T DO SOMETHING
LIKE A LUMEN EXPECTATIONS WHICH
IS LIMITED TO 8-12 BIOMARKERS OR
SO, BUT IT GENERATED 478 MARKERS
IN BLOOD THAT IF YOU LOOK AT IN
PRINCIPAL DEPUTY PAL COMPONENT
ANALYSIS COULD SEGGREGATE SEVERE
CF POPULATION AND LUNG FUNCTION
DECLINE PROGRESSION OVER THE
NEXT 3-24 MONTHS AND IT DID THAT
DURING STABLE DISEASE, SO THIS
IS NOT WHEN THEY'RE EXACERBATING
OR WHEN THEY'RE IN THE HOSPITAL
AND MEASURING WHICH MOST
BIOMARKERS DEVELOP FOR CFR AND
THIS IS WHEN THEY'RE IN STABLE
DISEASE AND THERE'S NO ISSUE.
AND YOU CAN SEE ON THE RIGHT
THERE, THAT OUR FIRST GENERATION
TEST FOR FIBROSIS, AND CF AND
OTHER DISEASES ACTUALLY HAS GOT
AN AUC OF 8.4, WHICH WE'RE NOW
DEVELOPING AND WE'RE VALIDATING
IN THE LARGE NUMBER OF SAMPLES
RIGHT NOW AND GETTING READY TO
GO BACK TOCCATAALIZE.
NEXT SLIDE, PLEASE.
I THINK WE CAN SKIP THIS 1.
IT'S A SUMMARY OF WHAT THE
TECHNOLOGY LOOKS LIKE.
NEXT SLIDE, PLEASE.
I THINK JUST THE KEY TAKE ARK
WAYS FOR ME WOULD BE BALANCE,
VISION WITH FEASIBILITY.
THINK ABOUT WHAT IS FEASIBLE
BECAUSE THAT WILL EFFECT THE
PRODUCT THAT YOU END UP MAKING,
I THINK IT'S -- YOU HAVE TO BE
GOOD AT BUILDING GOOD
COLLABORATIONS AND THEY HAVE TO
BE STRONG AND YOU ALSO HAVE TO
HAVE DISCUSSIONS THAT ARE VERY
TRANSPARENT, SOMETIMES
COLLABORATIONS DON'T GO IN THE
RIGHT DIRECTION AND WHAT
SOMEBODY'S PROVIDING TO THE TEAM
IS NOT ACTUALLY HELPING SOLVE
THE PROBLEM OR MAKE THE PRODUCT
BETTER OR IMPROVE THE PRODUCT OR
SCALE IT UP OR MARKET IT OR WHAT
HAVE YOU AND YOU HAVE TO EITHER,
YOU KNOW ADJUST OR FIND OTHER
COLLABORATORS.
SO IT IS SOMETHING THAT YOU HAVE
TO BE VERY GOOD AT DOING AND YOU
CAN'T JUST BE STUCK IN THE SAME
SORT OF MODE OF IGNORING WHAT
THE TARGET IS RATHER THAN JUST
TO BE NICE IN A SENSE AND I
THINK ALSO BE VERY CONSCIOUS OF
THE INSTITUTIONAL CAPACITY WHICH
IS ALWAYS A CHAL CHALLENGE ANDY
AGAIN BE TERRIBLE FOR
TRANSLATION EMPLOY SO YOU HAVE
TO BE A BIT SAVVY AND I THINK MY
ONLY NOTE WOULD BE IF THE NIH
CAME UP WITH MORE PROGRAMS LIKE
CATALYZE WHICH ACTUALLY
INCENTIVIZE INSTITUTIONS TO
REWARD, YOU KNOW HIGH RISK
INNOVATION, I THINK THAT THAT
WOULD SHIFT THE CULTURE IN THESE
ACADEMIC CENTERS BECAUSE REALLY
THEY JUST FOLLOW THE MONEY AND
THAT WOULD REALLY HAVE A BIG
IMPACT ON CATCHING A LOT OF THIS
MISSED OPPORTUNITY I THINK THAT
FALLS BY THE WAY SIDE BECAUSE
PEOPLE DON'T GO THROUGH THE
TROUBLE OR THEY'RE NOT SAVVY
ENOUGH TO NAVIGATE THE
ENVIRONMENT TO KEEP THEIR
TECHNOLOGIES ALIVE.
THAT'S IT FOR ME.
SORRY IT TOOK A BIT LONG.
>> ALL RIGHT.
>> WE WILL HAVE THE PANELISTS
COME ON THE CAMERA, WE WILL
SPOTLIGHT YOU.
>> THANK YOU VERY MUCH,
EVERYONE.
I THINK WE HAVE A REALLY
CONSISTENT MESSAGE HERE ALTHOUGH
DIFFERENT FROM THE DIFFERENT
PEOPLE.
WE DON'T HAVE ANY QUESTIONS FROM
THE AUDIENCE YET BUT I THOUGHT I
WOULD START BY ASKING INTERNAL
QUESTION WHICH IS WHAT DO YOU
THINK THE POINT AT WHICH OF
HAD-SO RESEARCHERS ARE PRETTY
GOOD AT COMING UP WITH TARGETS
BUT THEY'RE OFTEN BAD WITH ALL
OF THE REST OF IT.
WHAT DO YOU THINK THE -- WHAT
WOULD YOUR ADVICE BE TO SOMEBODY
WHO'S GOT SOMETHING THAT LOOKS
GOOD IN THEIR MOUSE OR WHATEVER
AND IS THINKING ABOUT TRYING TO
PUSH IT FURTHER?
AND IT'S FOR ANYBODY WHO THINKS
IT'S WORTH ANSWERING?
>> HIRE A GOOD CHEMIST.
>> [LAUGHTER]
>> THAT'S AN EXCELLENT ANSWER,
ACTUALLY.
>> I THINK MAYBE ON THAT FRONT,
IF THERE'S A GOOD TARGET
ESPECIALLY IF IT'S A NOVEL
TARGET THAT IS THE FIRST TIME
THAT ANYONE'S DISCOVERED THE
MECHANISM, A HUGE PART OF IT IS
REALLY SHOWING THAT IT CAN BE
REPRODUCED IN A DIFFERENT LAB,
THAT'S MAYBE A BIG AREA THAT
PREVENTS OTHERS FROM REALLY
INVESTING EARLY ON IN BIOLOGY IF
THE BIOLOGY'S ONLY EVER BEEN
DISCOVERED OR WORKED ON IN 1
LAB.
IT REALLY MAKES YOU OPEN UP THE
QUESTION OF JUST FROM INVESTORS,
YOU'RE NOT ON THE GROUND ALL THE
TIME TALKING WITH EVERYONE, IS
THAT THERE'S A VERY DIFFICULT
TECHNIQUE TO GET THERE, IS IT
THAT THE SCIENTIST IS LESS
LABRATIVE, THOSE ARE ALL THINGS
THAT PEOPLE CARE ABOUT QUITE A
LOT, JUST IN ADDITION TO THE
SCIENCE AND FROM THE PERSPECTIVE
OF HOW AND VENTURE CAPITAL YOU
RISK A TECHNOLOGY THAT SOMEBODY
COMES TO YOU WITH AND HOW DO YOU
LEVERAGE AND SORT OF BALANCE
THEIR VISION AGAINST THE REALITY
OF WHAT COULD BE ACHIEVED AND
HOW DO YOU ACTUALLY MAKE SURE
YOU'RE RIGHT AND IT'S NOT THEM
THAT'S RIGHT.
>> I WILL START, I THINK FROM
OUR POINT OF VIEW, WE'RE VERY
LUCKY WE HAVE OUR LABS IN
BOSTON, WITH ABOUT 50 PEOPLE, SO
WE'RE ABLE TO REALLY BRING IN
TECHNOLOGIES, AND THAT'S NOT
ONLY BENEFICIAL FOR US, BUT IT'S
BENEFICIAL FOR THE COMPANY, TOO,
BECAUSE WE ACT AS EXTERNAL
VALIDATION CAN TECHNOLOGY, AND
AT THE SAME TIME THEY CAN SEE
EARLY ON, IS THE TECHNOLOGY
GOING TO WORK IN CYSTIC FIBROSIS
MAYBE IT WON'T FOR CF AND
PROVIDE THAT DATA EARLY ON IN
THE PROCESS, AND THEN FROM OUR
SIDE, WE CAN SAY, OKAY THIS
WORKS WELL, HERE, LET'S MOVE
FORWARD, AND WE CAN GET EXCITED
ABOUT IT, AND HELP THEM.
NGREAT RESOURCE TO HAVE --
>> SO ON THAT FRONT IN THE
PROCESS OF DECIDING WHETHER OR
NOT WE WANT TO START THE COMPANY
OR TECHNOLOGY OR ASSET, WE
GENERALLY HAVE EXPERIMENTS THAT
WE WOULD LIKE ACADEMIC TO
PERFORM, WE DESIGNED EXPERIMENTS
GENERALLY, THERE ARE 1S THAT FOR
IN THE ACADEMIC WORLD BE LIKE
SUPPLEMENTAL FIGURE, 25, BUT FOR
US VERY IMPORTANT TO VALIDATE
IT, AND SO IF ALL THAT KIND OF
COMES BACK POSITIVE, OR IN THE
DIRECTION OF WE THINK MAKES
SENSE THAT HELPS GREATLY
VALIDATE THE TECHNOLOGY THAT'S
WORKING IN A WAY THAT WE'RE
SEEING THINGS AND HOW WE'RE
DESIGNING IT AND YOU'RE GETTING
IT LIVE.
JUST TO HAVE THAT EXTRA
CONFIRMATION.
>> AND THEN I THINK TO ADD
BEYOND CFF, WE SEE FORESIGHT
LABS TO CALL THEM, THEY'RE
MOVING ALSO TOWARDS A MODEL
WHERE THEY'RE ALSO ABLE TO
VALIDATE SOME OF THE
TECHNOLOGIES AND THEN IF YOU
TALK TO STRATEGIC PLANEGEYICS,
FOR EXAMPLE, WHERE IT WAS
BEFORE, THERE WAS ALSO CAPACITY
TO BE ABLE TO VALIDATE
TECHNOLOGIES, OR TO CO DEVELOP
ONCE A TARGET IS FOUND BRINGING
IN THE CHEMIST FROM BIOTO KIND
OF WORK ON THE TARGET
SPECIFICALLY WHILE THE SAME TIME
ENGAGING THE PI WHO MIGHT OR
MIGHT NOT WANT TO BE SUPER
INVOLVED IN IT, BUT THERE'S
DIFFERENT MODELS OUT THERE THAT
IT'S WORTH EXPLORING.
>> SO THERE'S A QUESTION IN THE
Q&A FROM CAITLIN
[INDISCERNIBLE].
WHAT ARE SIGNS THAT AN
INSTITUTION'S NOT SUPPORTING
SUPPORTING
INNOVATION OR RED FLAGS FOR
BUILDING YOUR CAREER AND
RESEARCH TRAINING?
>> I THINK IF YOU LOOK AT
PROMOTION IN MOST PLACES, IT
USED TO IN SOME PLACES A THING
THAT YOU GOT KUDOS FOR, BUT
THESE DAYS IT'S JUST PAPERS AND
FUNDING, RIGHT IN SO IF YOU
WANTED TO GET TENURE SOMEWHERE,
YOU KNOW, INNOVATION USED TO
COUNT BUT MOST PLACES ARE
ACTUALLY GETTING RID OF IT,
BECAUSE IT'S SUCH A HIGH RISK
AND IT REALLY IS HARD TO DEFINE.
I THINK IT'S EASIER TO DEFINE IF
YOU BASE IT ON THE SUCCESS IF
YOU BRING IT ON THE MARKET LIKE
SOMEBODY LIKE JAMES FOR
INSTANCE, SO ACADEMIA, SO THAT'S
1 PLACE TO LOOK, SEE WHAT YOUR
PROMOTION AND TENURE COMMITTEE
VIEWS INNOVATION AS AND THAT
TELLS WHAT YOU THAT INSTITUTION
VALUES INNOVATION AT, IS MY
OPINION ABOUT.
>> YEAH, GO AHEAD.
>> ONE ANGLE HERE, THERE'S A LOT
OF WAYS TO ANSWER THIS QUESTION,
1 ANGLE IS TO START WITH THE OTM
OFFICE, THE TECH TRANSFER
OFFICE.
AND YOU FIND SOME OF THE
PRESTIGIOUS COOLS HAVE EXTREMELY
OVERWORKED UNDERSTAFFED, UNDER
REWARDED GROUP THAT'S NOT HAPPY
TO TAKE ON MUCH OF ANYTHING SO
IF YOU INTERVIEW THE DIRECTOR OF
THE TECH TRANSFER OFFICE, YOU
COULD GET A LOT OF INSIGHT INTO
THE FLAVOR OF THE INSTITUTIONAL
PRIORITIES.
>> MOST OF THOSE WILL NOT HELP
YOU WITH YOUR CAREER, AS FAR AS
GETTING TENURED AND GETTING
PROMOTED, THE TECH TRANSFER
FOLKS HAVE VERY LITTLE, AT LEAST
MOST THE PLACES I'VE BEEN, IT
MAY BE DIFFERENT DR. HOLTZMAN,
BUT THE INSTITUTIONS I'M AT THE
TECH TRANSFER PEOPLE ARE THERE
AND THEY'RE SUPPORTIVE.
THEY'RE USUALLY THE SILVER
LINING AT THESE PLACES, BUT MOST
OF THEM HAVE IMPACT ON WHETHER
YOU GET PROMOTED OR TENURE AND
THAT IS THE INSTITUTIONAL
SUPPORT OF THIS.
YOU KNOW AND I'VE SEEN A LOT OF
VERY SMART INNOVATIVE PEOPLE
DECIDE NOT TO INNOVATE BECAUSE
IT DISTRACTED THEM FROM GETTING
THE INCREMENTAL GRANTS AND
GETTING THE PAPERS AND MOVING ON
WITH THEIR CAREER.
YOU KNOW?
AND THATIA A PROBLEM, NOBODY
TALKS ABOUT IT, MAYBE IT'S NOT
AS BIG A PROBLEM AS I'VE SEEN
BUT IT IS A PROBLEM.
NYEAH, I CERTAINLY DON'T
DISAGREE,Y JUST WAS TRYING TO
MAKE THE POINT THAT IF IT'S AN
INSTITUTIONAL PRIORITY TELL BE
AS WELL QUEPED AS SOME OF WHAT
THE GUYS ARE CALLING INCREMENTAL
SUPPORT SYSTEM.
SO IF YOU WALK IN THERE AND
THERE'S ONLY 1 PERSON ON A
KEYBOARD, YOU PROBABLY NOT GOING
TO MAKE A LOT OF PROGRESS IN
THAT ENVIRONMENT, AND THE REASON
THAT'S THE CASE OFTEN IN THE
MIDWEST, I NOTICE, LIKE FROM
LUCY'S SLIDES THERE'S A LOT OF
COASTAL ACTIVITY AND NOT MUCH IN
THE MIDDLE WHEREAS A LOT OF
PEOPLE ON THIS CALL ACTUALLY ARE
IN THE MITSD BUT 1 OF THE
REASONS FOR THAT IS IT'S A VERY
UNDERDEVELOPED PATHWAY.
AND IT STARTS AT THE LEVEL
YOU'RE REFERRING TO IN THE
ACADEMIC SETTING AND IT MOVES
RIGHT ON THROUGH THE BIOCHECK
AND D. C. SECTOR AS WELL, IF
IT'S WELL DEVELOPED USUALLY THAT
OFFICE WILL RECOGNIZE IT AND
SHOULD BE SUPPORTED FOR IT BUT
IF IT'S NOT, YOU WILL HAVE AN
UPHILL BATTLE.
>> I WOULD ADD HERE THAT IN THE
CAREER, AS SOMEBODY WHO
[INDISCERNIBLE] ACADEMIA AND
TART THE SUMP AND THAT --
COMPANIES AND WITH THAT IN MIND,
TALKING TO THE TECH TRANSFER
OFFICE HELPFUL AND THEN
UNDERSTAND THE PROCESS OF TAKING
AN IP OUT OF THE UNIVERSITY AND
GO TO A COMPANY, WHAT ARE THE
REQUIREMENTS FROM THE UNIVERSITY
SIDE WHERE SOME UNIVERSITIES
MIGHT BE ASKING FOR A LOT, AND
THAT MIGHT BE SCARY AND OTHERS
AWAY OR INVESTORS SO REALLY
TRYING TO UNDERSTAND WHAT THE
UNIVERSITY REQUIRES, IS IT BOARD
SEATS, IS IT SPECIFIC EQUITY AND
THEN TRY TO UNDERSTAND, OKAY,
ASK THAT MODEL THERE TO
SUCCESSFUL COMPANIES AS BEING
ABLE TO ATTRACT OTHER PARTNERS
AND INVESTORS AND TRYING TO
UNDERSTAND IF IT FITS WITH WHAT
YOU WANT TO DO WITH YOUR CAREER
NGREAT.
AND THE OTHER THING TO THAT
COMMENT OR WHAT EVERY WE CALL
THEM THESE DAYS, LOOK FOR ROLE
MODELS, WHOSE DONE THIS AT THIS
PLACE AND WHAT'S THERE
PERSPECTIVE ON TRYING TO GET IT
DONE IN THAT ENVIRONMENT AND IF
YOU'RE NOT FINDING ANY, OR EVEN
IF THEY DO AND THEY EXPRESS
FRUSTRATION, ONCE AGAIN, YOU'RE
PROBABLY LOOKING AT A LOT OF
OBSTACLES.
>> I'VE ONLY 11 THING TO ADD ON
THIS IS THAT EVEN THOUGH OUTSIDE
OF UNIVERSITY, I'M AT VANNEDDER
BILL, VANDERBILT MEDICAL COOL IS
#1 IN NIH FUNDING, SO WE ATTRACT
A LOT OF FUNDING, THE STUDENTS
ARE EXCITED ABOUT TECH TRANSFERS
BUT THERE'S NO INFRASTRUCTURE,
NO INCUBATORS, NO OUTSIDE MOUSE
FACILITIES, 1 OF THE LAST
SPIN-OFF COMPANY I DID I
LITERALLY HAD TO SET UP A LAB
UNDERNEATH A REALLY NICE BAR
DOWN TOWN, BUT YOU KNOW IT'S --
SOME PLACES IT'S HARD TO
SPIN-OFF COMPANIES BECAUSE
THERE'S NO PLACE TO DO IT TO.
>> RIGHT.
CREATING THAT KIND OF
ENVIRONMENT'S CHALLENGING.
WE HAVE THE SAME ISSUE IN
ST. LOUIS AND THEN WE HAVE LOTS
OF OTHER ISSUES THAT GO TO THE
MAYOR BUT HAVING THAT IS A
CHALLENGE FOR THE MIDWEST IN
GENERAL.
A LITTLE BIT IN CHICAGO, SIN
SUDDEN ATY CHILDRENS HAS DONE A
BETTER JOB I THINK THAN MOST
PLACES BUT THERE'S A LOT OF RISK
ADVERSITY IN WHAT WE'RE CALLING
TRANSLATIONAL RESEARCH AND
ST. LOUIS, 1 OF THE REASONS
WE'RE NOT GROWING AS A
METROPOLITAN AREA IS THAT
THERE'S A VERY RISK ADVERSE
APPROACH TO ALL KINDS OF
ACTIVITY ANDS THAT INCLUDES
MEDICINE.
>> IN GENERAL, YEAH, YEAH.
>> I WANTED TO --
>> I HAVE A QUESTION FOR
ENRIQUE, YOU MENTIONED THE
FOUNDATION HAS GUIDELINES OF
AISK -- BASICALLY A PATH TO
COMMERCIALIZATION OR A PATH TO A
CURE.
THESE GUIDELINES ARE PUT
TOGETHER BY THE LAB, BY PFIZERS
ACADEMIC AND THE ACADEMIC
COMMUNITY, IT'S BASICALLY SORT
OF A WHITE PAPER ON WHAT THE
FOUNDATION THINKS, HOW MUCH
FRICTION DO YOU SEE BETWEEN
THESE GUIDELINES AND SORT OF
INDIVIDUAL VISIONS OF THERAPIES
FOR CF THAT YOU ENCOUNTERED.
YOU SEE A LOT OF FRICTION OR DO
PEOPLE USUALLY JUST GO ALONG
WITH ALL THE LITTLE CHECK
CONTROLLER OF BANKS THAT YOU
HAVE?
>> YEAH, I WOULD SAY WE HAVEN'T
SEEN TOO MUCH FRICTION.
THE GUIDANCE THAT WE PRESENTED
TODAY ARE REALLY FOCUSED ON
PRECLINICAL GENETIC MEDICINES
AND VERY EARLY STAGE COMPANIES
AND WE TRY TO ENGAGE COMPANIES
AT EARLY STAGE SO WE IMPLEMENT
THOSE GUIDANCE EARLY ON AND HELP
COMPANIES GET ON THAT CHECK LIST
FROM THE BEGINNING.
SO WHEN THEY COME TO US, WE HAVE
SPECIFIC CF DATA WE ARE ALIGNED
IN TERMS OF LOOK FOR EXAMPLE THE
SAME THINGS.
ARE YOU DEMONSTRATING IN THE
GOLD STANDARD EXPERIMENTS THAT
YOUR APPROACH IS WORKING IN
CYSTIC FIBROSIS, SO I WOULD SAY
WE HAVE REALLY ENCOUNTERED TOO
MUCH PUSH BACK AROUND THOSE
GUIDE LINES OR PARALLEL
APPROACHES TO GETTING TO THE
SAME RESULT.
I THINK THE CF COMMITTEE QUITE
UNIQUE IN TERMS OF HOW THEIR
RESOURCES AND HOW, THE
COMMITTEE'S QUITE CLOSE AND THEN
HOW THESE RESOURCES ARE OPEN AND
PEOPLE ARE ABLE TO ACCESS AND
UNDERSTAND WHAT'S NEEDED TO MOVE
THERAPY FORWARD.
>> WAS THAT QUESTION DIRECTED AT
ALL TO THE COMMON STREET NOTICES
THAT THE CFF LIKES TO TAKE A
PIECE OF THE PROFITS IN THE
PROCESS?
>> I MEAN I THINK IF THEY
INVEST, THEY HAVE A RIGHT TO ASK
FOR THAT.
NTHAT'S WHAT I'M ASKING.
>> I THINK HA THEY GET DINGED
UNFAIRLY I THINK FOR WHAT HAPPEN
WIDE VERTEX, WHEN YOU THINK
ABOUT IT THEY WOULD HAVE NEVER
GONE DOWN THE TRACK WITHOUT THE
FOUNDATION A INVESTMENT SO
WHETHER YOU WANT TO TALK ABOUT
GREED OR WHATEVER, YOU KNOW IT
WOULDN'T HAVE HAPPENED WITHOUT
BOB BELL INVESTING IN VERTEX,
AND NOW, CF PATIENTS HAVE THIS
DRUG.
SO IT'S 1 OF THESE KINDS OF
THINGS WHERE REALLY CAN YOU PUT
1 SIDE TO BALANCE, YOU KNOW?
MAYBE THERE SHOULD BE MORE
ADVOCACY ON MAKING THE DRUGS
CHEAPER, MAYBE I'LL --
[LAUGHTER]
>> I DO SAY WE -- NDON'T GET MAD
AT ME NWE DO HAVE VERY
[INDISCERNIBLE] AS WELL, WE DO
NOT HAVE THE ABILITY TO CONVINCE
A PHARMACEUTICAL COMPANY OR TO
DISCUSS PRICING WITH
PHARMACEUTICAL COMPANY.
I WOULD SAY VENTURE PHILANTHROPY
WHICH YOU HAVE MENTIONED IS
REALLY KIND OF SOMETHING THAT
WAS PIE OR NEARED BY THE
FOUNDATION -- PIONEERED BY THE
FOUND FOUNDATION AND IT'S
ALLOWED US TO TACKLE A LOT OF
THE DIFFERENT CHALLENGES WHEN IT
COMES TO CYSTIC FIBROSIS AND
THEN WE'RE REALLY TRYING TO --
OR I'VE SEEN A LOT OF
FOUNDATIONS TAKE THIS APPROACH
AS WELL, BECAUSE ALL FOUNDATIONS
ARE LOOKING FOR SUSTAINABLE WAYS
TO CONTINUE MOVING TOWARDS THEIR
MISSION.
AS YOU KNOW GETTING TO CURE
CYSTIC FIBROSIS OR ANY GENETIC
DEC IS NOT CHEAP OR EASY AND
IT'S GOING TO TAKE TIME, SO
THAT'S 1 WAY WE'RE TRYING TO
ACHIEVE HERE.
>> OKAY, DO YOU FEEL -- I WILL
PUSH THE BUTTONS HERE SINCE
NOBODY ELSE WANTS TO.
SO IT'S THE ISSUE OF THE MISSION
ENRIQUE.
SO WHEN I WAS A CHILD, YOU KNOW,
CHARITABLE FOUNDATIONS SUPPORTED
RESEARCH FOR RESEARCH SAKE AND
THEY DIDN'T CAN A LOT OF
QUESTIONS ABOUT THE IP ON A
MONTHLY BASIS EVEN.
SO IT DOES CHANGE THE
TRAJECTORY, THERE'S NOTHING
WRONG WITH BEHAVING LIKE A VC IN
SOME SENSE BUT IT DOES -- I
THINK TO SAY, IT'S ALL FOR 1 AND
1 FOR ALL KIND OF THING IF THE
PATIENT BENEFITS IT'S NOT QUITE
THE FULL STORY ON HOW THINGS
HAVE SHIFTED AND I -- SOME OF
THE DPRAITEST DISCOVERIES, OF
MEDICINES AND THERE AREN'T MANY,
RIGHT, CAME OUT OF VERY BASIC
RESEARCH, THAT NOBODY WOULD HAVE
INVESTED FOR COMMERCIAL ELEMENT,
SO SOMETIMES THOSE ENTERPRISES
WILL SUFFER BECAUSE THEY DON'T
PORTRAY A DIRECT ROUTE TO THE
MARKETPLACE AND THAT'S GOING TO
HAPPEN MORE OFTEN THAN NOT.
>> I AGREE AND I THINK WE'RE ON
THE SAME PAGE, THE CF FOUNDATION
ALSO FUNDS ACADEMICS AND THAT IS
COMPLETELY NO STRINGS ATTACHED
AND WE FUND ALMOST THE SAME
AMOUNT IN FOUNDATIONS AND
RESEARCH IN THE CF COMMUNITY
THAT ARE VERY BASIC WITHOUT
EXPECTING ANY RETURNS.
>> WE GOT A BIT OFF TOPIC ON
WHAT THE PANEL IS SUPPOSED TO BE
ON, NOT THAT I DON'T THINK
VENTURE FILL AN THOPY IS NOT
WONDERFUL BUT -- [LAUGHTER]
>> LET ME COME FROM THE FEDERAL
GOVERNMENT PERSPECTIVE AND THE
PARTNERSHIP WE'VE BEEN ABLE TO
HAVE WITH THE FOUNDATION, YOU
KNOW THE INVESTMENT DOES HAVE
RETURN BUT THEN IT CONTINUES TO
BE REINVESTED INTO THE COMMUNITY
AS ENRIQUE HAS SAID, SO WE
WOULDN'T HAVE NEW PROGRAMMING
LIKE PATH TO THE CURE WHICH IS
HEAVILY INVESTING IN THERAPIES
OR GENE THERAPIES THAT ARE LEFT
BEHIND FROM VERTEX, AND THEY
HELPED TACKLE THE SITUATION OF
GETTING A DISEASE MODIFYING
THERAPY TO MARKET, BY SUPPORTING
VERTEX, CONTINUE TO INVEST INTO
BASIC SCIENCE AND THEN IN TURN,
CREATE HIGH RISK, HIGH REWARD
PROGRAMS THAT THE NIH CERTAINLY
CAN'T NECESSARILY DO AT THE SAME
SCALE BECAUSE WE DON'T HAVE THAT
CAPITAL.
WE DO HAVE PROGRAMS THAT WE DO
TRY TO DO IN PARALLEL AND IN
PARTNERSHIP WITH THE FOUNDATION,
AND YOU KNOW TRY TO HAVE THOSE
COLLABORATIVE EFFORTS TO MAKE
SURE THAT YOU KNOW THE SPACE IS
WELL FUNDED AND SO I THINK THAT
FROM A GOVERNMENT PERSPECTIVE,
LIKE WE COULDN'T REALLY HAVE THE
TYPE OF SCIENTIFIC PORTFOLIO
THAT WE DO THAT IS SO SUCCESSFUL
IN CF, WITHOUT THAT TYPE OF
STRATEGY, AND WHAT WOULD BE
BEAUTIFUL --
>> [INDISCERNIBLE] MENTIONED
THAT AS WELL.
>> JOHN, YEAH, YEAH PUT THAT IN
THE Q&A AS WELL.
WHAT'S BEAUTIFUL ABOUT THAT IS
IT'S A MODEL I THINK WE SHOULD
LEARN FROM.
I THINK THAT OTHER ORGANIZATIONS
ARE ALREADY COMING UP ON THAT
AND WE WILL HEAR FROM SOME OF
THEM TOMORROW ABOUT SHARED
LEARNING FROM THE FOUNDATION AND
HOW THEY'RE ABLE TO CATALYZE
RESEARCH AND INDUSTRY
PARTNERSHIPS, IN SIMILAR WAYS,
YOU KNOW BUILDING UP THEIR
PROFILE, SO, YOU KNOW, THE KEY,
I THINK IS THE VENTURE
PHILANTHROPY PIECE OF IT IS THAT
WHATEVER COMES IN, ALSO GOES
BACK OUT.
BUT, YEAH, I JUST WANTED TO ADD
THAT, AS VIEWING IT FROM THE
LENS OF WHERE WE ARE ON THE SIDE
OF HAVING PARTNERSHIPS WITH THE
FOUNDATION BUT I CAME INTO THE
PANEL BECAUSE AS A CO-HOST I
CAN'T ASK A QUESTION AND WANTED
TO ASK THE QUESTION, --I REALLY
WANTED TO FOLLOW UP ON THE PEER
TO PEER M-TEBURKEULOSEIS
-- MENTORING AND CONTACTS, WE
TRY TO GET THE PEER TO PEER
PROGRAM, AND THEY ARE AT THE
COMMITTEE MEETINGS AND THEY THEY
MEET AND THEY WORK TOGETHER WHEN
THEY CAN AND THEY SORT OF CROSS
TALK WHEN THEY MAKE SENSE, BUT I
WONDERED IF YOU ALL HAD OTHER
IDEAS OF HOW PEOPLE CAN BETTER
LEARN FROM EACH OTHER, THAT'S
BASICALLY PART OF THE PLATFORM,
WE'RE TRYING WITH THIS WORKSHOP,
IS TO BRING IN EXPERTS LIKE YOU
ALL, BUT YOU KNOW IT'S SO
EXPENSIVE AND SO HARD TO DEVELOP
THESE NOVEL TECHNOLOGIES AND
INTERVENTIONS AND DRUGS OR GENE
THERAPY, WHATEVER THEY MAY BE,
HOW CAN WE FIND BETTER WAYS TO
GET PEOPLE TO PEER MENTOR EACH
OTHER THROUGH THE PROCESS, AND I
ASK THAT BECAUSE WE'RE ACTUALLY
EVEN TRYING THAT HERE AT THE
NIH, SO THE SOMATIC CELL GENOME
EDITING PROGRAM IS IN PHASE 2,
IT'S FUNDED BY THE COMMON FUND
AND WE ARE HAVING A GROUP OF
INVESTIGATORS WORKING TOGETHER
ACROSS DISEASES, TO LEARN FROM
INTERACTIONS WITH THE FDA IN
ORDER TO STREAMLINE GENE THERAPY
APPROVALS THROUGH THE FDA.
AND SO, WE'RE PILOTING THAT BUT
THAT'S ONLY 1 PROGRAM AT THE
NIH, AND I'M JUST THINKING IF
THERE ARE STRATEGIES YOU CAN
THINK OF HOW THE COMMUNITY CAN
BE BETTER AT PEER TO PEER
MENTORING TO SORT OF HELP
CATALYZE INNOVATION AND EVEN
PREVENT KIND OF COMPETITION AND
REALLY HAVE THIS SHARED GOAL FOR
ESPECIALLY FOR RARE DISEASES.
>> YOU CAN HAVE -- YOU CAN HAVE
THE GRANTS MAYBE REQUIRE OR YOU
KNOW SUGGIEST OR ADVISE FOR
CONSULTANT ON THERE FOR INSTANCE
IS SOMEBODY THAT'S SEASONED SO
THAT IF SOMEBODY'S TRYING THIS
FOR THE FIRST TIME THEY MAY FIND
DR. HOLTZMAN AND DR. WEST TO
PARTNER WITH THEM EVEN IF IT'S
NOT THE SAME TECHNOLOGY.
SPEAKING OF THE FOUNDATION BEING
AN EXAMPLE, THAT'S SOMETHING
THIS WHEN THEY COME IN TO DO
RESEARCH, IF YOU HAVENER DONE
RESEARCH BEFORE, THEY LIKE TO
HAVE SOMEBODY WITH RESEARCH AS A
COLLABORATOR BUT THEY'RE OPEN TO
YOU COMING INTO THE CF FIELD AS
LONG AS DO YOU THAT SO IT'S THE
WAY THEY PROMOTE PEOPLE LEARNING
ABOUT CF.
>> CAN I COMMENT ON SOMETHING,
THIS IS JOHN ENG LEHEART, I WILL
MAKE 1 COMMENT ABOUT THE STORY
LUCY TOLD ABOUT COLLABORATION,
THEY WERE TALKING ABOUT THE GENE
THERAPY SPACE AND I TRIED TO
CONVINCE BIG PHARMA TO GET
INVOLVED IN THAT, AND WHEN
PFIZER DID TAKE IT UP FOR A
WHILE BUT DIDN'T WANT TO
CONTINUE WITH IT AND YOU KNOW I
WOULD SAY SO FROM MY
PERSPECTIVE, I COULDN'T QUIT MY
DAY JOB TO MAKE THE COMPANY, AND
THOSE SORT OF INFORMA GET
TOGETHERS ARE GATHERING BETWEEN
VC OR INVESTORS IN THAT SPACE
THAT ARE SCIENTISTS AND WANT TO
HEAR ABOUT THE LATEST
TECHNOLOGY, AT ANY SORT OF
CONFERENCE, WOULD BE -- MIGHT
REPLICATE THAT TYPE OF THING
BECAUSE I NEVER WOULD HAVE
PREDICTED THAT THAT WOULD HAVE
BEEN THE OUTCOME.
>> NIH INNOVATORS CONFERENCE.
>> YEAH, I WAS GOING TO SAY, I
HAPPEN TO BE ON THE KEY STONE
BOARD SO I PASSED ALL OF THIS
INFORMATION ON TO THEM AS AN
IDEA FOR A KEY STONE SYMPOSIA
FOR NO OTHER BASIS BECAUSE WE
DON'T -- WE REALLY HAVE
SPECIALIZED HIGH SCIENCE, KIND
OF DRUG ORYEBTED MEETINGS BUT WE
DON'T HAVE THIS WHERE YOU TAKE A
MORE GENERALIZED APPROACH TO
BRING PEOPLE TOGETHER IN THIS
SPACE TO DO WHAT WE'RE DOING
TODAY AND TOMORROW AND SO WE'LL
SEE WHERE THAT GOES, BUT I THINK
THAT KIND OF FORUM, YOU KNOW,
EVEN GORDON, YOU KNOW THERE ARE
A LOT OF THESE, YOU KNOW PLACES
--
>> COLD SPRING HARBOR.
>> YEAH, I WAS JUST BLOCKING ON
THAT NAME.
BUT YEAH, THERE ARE
OPPORTUNITIES TO --
>> SO NONE OF US ARE GOING TO
LIKELY GO TO J. P. MORGAN SO
HAVING THOSE KIND OF SETTINGS,
WHERE YOU CAN BRING HIGH SCIENCE
TOGETHER WITH PEOPLE IN THE VC,
INVESTOR SPACE, I THINK WOULD BE
VERY INTERESTING AND YOU KNOW
WHAT YOU SPEND A FEW DAYS
TOGETHER LIKE THAT, GOOD IDEAS
COME FORWARD AND GET SUPPORTED.
SO I'LL GET BACK TO YOU ON HOW
IT GOES WITH THE KEY STONE
LEADERSHIP BUT I THINK THAT
WE'RE NOT REALLY DOING THAT AT
PRESENT.
USUALLY IT'S THE HOT PAPER THAT
GETS INVITED.
IT'S NOT SOMEBODY WHO'S TRYING
TO START A COMPANY.
>> AND I KNOW THAT ARE THERE
THESE INVESTOR MEETINGS AND
THEY'RE VERY GIG -- BIG AND ITS
HARD TO GO THERE AND FEEL
CONNECTED.
I TALK TO PEOPLE AND THEY'RE
LIKE, I DON'T KNOW WHO TO TALK
TO, WHERE TO GO, THERE'S SO MUCH
GOING ON HERE THAT MAYBE A
SMALLER VENUE STRUCTURA AS
YOU'RE SAYING MIGHT WORK BETTER
BECAUSE IT WILL HAVE A FOCUS, IT
WILL BE LONG, IT'LL BE SLEEP,
IT'LL BE RARE LUNG DECS, IT'LL
BE CHRONIC LUNG DECS, WHATEVER
IT IS, IT MIGHT BE A LITTLE MORE
FOCUSED AND EASIER FOR PEOPLE TO
CONNECT WITH EACH OTHER.
>> RIGHT.
EARLIER STAGE WITH SMALLER FOLKS
THAT MIGHT NOT GET INVITED TO
THE BIG SAN FRANCISCO MEETING OR
SOMETHING.
>> WE WILL SAY THAT WE HAVE
WORKED WITH THE CF FOUNDATION ON
CONCEPTS EXACTLY LIKE THAT, AND
I THINK THE FOUNDATION HAS DONE
THIS A FEW TIMES, MAYBE, WITH
LONG WOOD AND ALSO SEPARATELY
THEMSELVES ON JUST NO 1 HAS
ANYTHING SPECIFIC QUITE YET TO
START A COMPANY AROUND BUT THERE
IS A THESIS THAT WE'RE
INTERESTED IN AND WHETHER IT'S
DELIVERY OR IT'S OPPORTUNITIES
TO FIGURE OUT CARGOS, VERY
SPECIFIC, AND 1 THING THAT KIND
OF CATALYZES THIS IS THAT PEOPLE
NEED TO BE ABLE TO GET
COMFORTABLE WITH SHARING
UNPUBLISHED DATA AND THEN BEING
A LITTLE BIT MORE OPEN WITH THE
THINGS THAT THEY'RE WORKING ON
WHICH I KNOW IS DIFFICULT
BECAUSE, YOU KNOW SCOOPING AND
EVERYTHING ELSE BUT I KNOW WHEN
WE'VE STARTED THESE KIND OF
CONVERSATIONS IT'S ALWAYS A --
LET'S PLAN OUT AND WE TALKED
WITH ENRIQUE ABOUT THIS, WHO
WOULD BE IN THE SAME ROOM WITH
WHO WITHOUT A FEAR OF POTENTIAL
COMPETITION AND THEN GETTING
THAT TOGETHER TOCCATAALIZE THE
CONVERSATION.
SO IT'S ALWAYS NICE TO BE ABLE
TO BRING FOLKS TOGETHER AROUND
SPECIFIC TOPICS BUT I GUESS
THERE'S DIFFERENT COMPLICATIONS
THAT ARISE THAT REALLY, MAYBE
LIMIT THE CONVERSATION IN A
PARTICULAR WAY, BUT THENOT OTHER
HAND, I THINK THERE'S ALWAYS --
I THINK PEOPLE ARE OPEN TO
TALKING, IF YOU FIND VENTURE
CREATION GROUPS WHICH I THINK
MOST GROUPS ADVERTISE QUITE
LOUDLY THAT THEY ARE AND YOU
WANT TO THROW OUT SOME IDEAS
ABOUT A PARTICULAR THING, NOT
THAT YOU HAVE A PARTICULAR
TECHNOLOGY, BUT JUST HEY, WHAT
ABOUT THIS GENERAL TOPIC.
THAT'S ALWAYS A CONVERSATION
THAT COULD BE OPEN FROM THE
OTHER DIRECTION AS WELL, INSTEAD
OF WAITING FOR OUTREACH OR
SOMETHING LIKE THAT.
>> YOU KNOW, IN SOME WAYS
CATALYZE HAS ALREADY ACHIEVED
SOME OF THAT AND HOW THEY BRING
ALL THE INVESTIGATORS TOGETHER,
AND YOU KNOW MAYBE YOU CAN
EXPAND ON THAT, MA RRAH AND GROW
THAT MODEL.
IN THERE YOU HAVE A BUNCH OF
INNOVATORS THAT COME TOGETHER
BECAUSE THEY'RE IN THE PROGRAM
AND IT SORT OF GRANDFATHERS IN
THE PEOPLE THAT GOT FUNDING
BEFORE, TOO, I STILL GET ALL THE
INVITES AND EVERYTHING, SO HAVE
YOU A STRUCTURE THERE THAT MAY
ACTUALLY BE SOMETHING THAT CAN
TURN INTO A COLLABORATION
BETWEEN GOVERNMENT, VENTURE
FOUNDATION AND ACADEMIA, THAT
COULD GROW, MAYBE AND REALLY
CAPTURE THIS INNOVATION SPACE
THAT A LOT OF FUNDING MECHANISMS
RIGHT NOW DON'T NECESSARILY DO.
>> YEAH, RIEWR RIGHT.
WE TRY TO KEEP PEOPLE QUOTE IN
THE PROGRAM EVEN AFTER THEY SUN
SET FROM THEIR GRANT BECAUSE YOU
NEVER KNOW WHAT YOU'RE GOING TO
BENEFIT FROM THROUGH THE WEBINAR
SERIES AND ALL THE PROGRAMMING
THAT RTI HELP SUPPORT, YOU KNOW,
THE NETWORK WILL GROW BIGGER AS
MORE PEOPLE GET FUNDED AND THEN,
YOU KNOW MAYBE THAT PEER TO PEER
MODEL WILL CONTINUE TO BE MORE
SUCCESSFUL, I THINK WE'RE ON OUR
THIRD RENEWAL OF THAT PROGRAM
WITH THE RECEIPT BASE I JUST PUT
IN THE CHAT EARLIER TODAY, SO
IT'S STILL KIND OF A NEWISH AND
I THINK WE'RE LEARNING AND MIKE
HAS BEEN A STELLAR LEADER IN
THAT PROGRAM AND CERTAINLY WE
CAN TAKE THAT FEEDBACK TO HIM AS
WELL.
>> AND THEN YEAH, I WONDER IF
IT'S WORTH THINKING ABOUT MAYBE
A SMALL SCALE PARTNER ASK
CONFERENCE TYPE OF MEETING WHERE
YOU CAN STILL HAVE THOSE 30
MINUTE MEETINGS, BUT AT A MORE
SPECIFIC TOPIC BASE, STILL
INVITE VCs AND INVESTORS BUT
THEN NOT HAVE THE GIANT J. P.
MORGAN WHICH IN MANY WAYS IT'S
SO BIG, IT'S OVERWHELMING EVEN
FOR PEOPLE LIKE LARGE INVESTORS.
>> CAN I ASK LUCY, ALL YOU CF
GUYS, DOES THIS HAPPEN AT THE
CF, IS THERE SORT OF A SATELLITE
MEETING WITHIN THE MEETING AT
THE CF MEETING THAT ATTACKS THIS
KIND OF PROBLEM?
,
YOU KNOW BRINGING WHAT WE TALK
ABOUT IN A SENSE?
>> SO SOME OF THAT HAPPENS AT
CFAC, AND THEY COME TO CFAC, THE
SUMMER RESEARCH CONFERENCE AS
WELL AS SOMETIMES BUT WE DON'T
NECESSARILY HAVE THE FORUM OR
THE VENUE JUST YET.
WE DO GO TO A LOT OF CONFERENCES
AND DO A LOT OF OUTBOUND
OUTSOURCING BECAUSE THERE IS --
THIS IS LIKE SOMETHING I STARTED
WHEN I WAS A KID, HAS NOW GROWN
INTO RAIS, THE RESPIRATORY
INNOVATION SUMMIT.
I DON'T KNOW IF ANYBODY'S
FAMILIAR WITH THAT SO THAT
HAPPENS ON THE FRIDAY AND
SATURDAY BEFORE ATS BEGINS AND
THAT'S ESSENTIALLY FORUM FOR
SMALL COMPANIES TO COME AND
PRESENT EARLY STAGE WORK AND
PITCH, YOU KNOW FOR FURTHER
FUNDING.
IT'S NOW UP TO SEVERAL HUNDRED
PEOPLE THAT TBET TOGETHER, WITH
POSTERS AND TALKS, IN AN EFFORT
TO BRING INVESTORS AND FOUNDERS
TOGETHER, YOU KNOW AT AN EARLY
STAGE.
SO AM I THE ONLY 1 THAT KNOWS
ABOUT IT?
IS THAT BAD IN.
>> I DEFINITELY KNOW ABOUT IT,
IT'S A GOOD FORUM, PART OF THE
SITUATION WITH AT LEAST IN MY
EXPERIENCE IS THAT, IT'S NOT
QUITE ADDRESSING RARE NEEDS.
I THINK THAT, YOU KNOW THEY HAVE
THE PARWHICH IS ANOTHER MEETING
THAT HAPPENS ON SATURDAY WITH
THE ADVOCACY EFFICACY SUBGROUP,
THAT THERE NEEDS TO BE A GROUP
FOCUSED ON LUNG DISORDERS WITHIN
THE INNOVATION SUMMIT OR
ENCOURAGING THAT PEOPLE TO COME
THERE, WITH THAT MISSION AND SO
THEIR PARTICIPATING WITH THE
SMALLER AND LARGER GROUPS THAT
ARE AT THE SUMMIT.
>> YEAH.
>> I WAS JUST GETTING AT THE
GENERAL NOTION, NOT THE RARE
DISEASE BUT YOU'RE RIGHT, IT'S
MORE ALL COMERS AND RESPIRATORY
DISEASE.
>> I THINK WE'RE OVER TIME, DO
WE STILL --
>> YEAH, I JUST WANTED TO
TRANSITION INTO CLOSING OF THE
WORKSHOP, SO WE STAY ON SCHEDULE
FOR TODAY AND I INVITED CAITLIN
AND JEFF TO GIVE A FEW WORDS
ABOUT, YOU KNOW GENERAL TAKE
AWAYS FROM TODAY AND THEN ALSO A
LITTLE BIT ABOUT WHAT WE'RE
GOING TO BE DOING TOMORROW.
SO YOU KNOW FOLKS THAT ARE STILL
ON THE CALL CAN YOU KNOW THINK
ABOUT THE STRATEGIES WE'RE GOING
TO TAKE FROM TODAY'S DISCUSSION
AND SORT OF BRIDGE IT INTO
TOMORROW'S SESSIONS AS WELL.
>> WELL, I WOULD BE HAPPY TO
KICK THAT OFF.
I JUST WANT TO START OUT BY
THANKING ALL THE SPEAKERS TODAY
IN THE PANELISTS AND EVERYONE
DID A FANTASTIC YOB CORPS AND
WALKING THROUGH THE YOWRNY IT
TAKES TO GO FROM AN IDEA OR
CONCEPT AROUND A THERAPEUTIC AND
JUST HOW MUCH WORK IS INVOLVED
TO MATURE THAT IDEA INTO A DRUG
ASSET, AND IN PARTNERING AS
WE'VE HEARD IN THIS GREAT
DISCUSSION TODAY AROUND WORKING
WITH REGULATORS AND ULTIMATELY
VENTURE CAPITAL AND OTHER
MECHANISMS THROUGH THE
GOVERNMENT OR OTHERWISE TO TRY
AND GENERATE FUNDS TO DEVELOP
THESE THERAPIES BECAUSE IT IS
VERY MUCH A TEAM SPORT AND THERE
ARE A LOT OF EXPERTS THAT YOU
NEED TO TALK TO THAT -- AND
THANKFULLY, THERE'S GROUPS LIKE
THE CYSTIC FIBROSIS FOUNDATION
AND THE CHILDHOOD INTERSTITIAL
LUNG DEC GROUP THAT ARE OUT
THERE THAT YOU CAN PARTNER WITH
TO GET EDUCATED ON THESE
DIFFERENT DISEASES, AS YOU'RE
TRYING TO MATURE YOUR ASSETS TO
THE CLINIC.
SO I THINK, WE LEARNED A LOT OF
GREAT LESSONS TODAY AROUND
TRYING TO GET US TO THE CLINIC
AND THAT'S A PERFECT SET UP FOR
CAITLIN AROUND WHERE WE'RE
HEADED TO TOMORROW.
>> WAY TO PASS THE BATON.
YEAH, REALLY GREAT SESSION,
TODAY, MAKES ME APPRECIATE ALL
THE BASIC SCIENCE RESEARCHERS
AND THE PEOPLE THAT ARE IN THE
TRENCHES, FAILING MORE OFTEN
THAT YOU SUCCEED SO THAT WE CAN
ACTUALLY MAKE POSITIVE CHANGE SO
THANKS TO ALL OF YOU WHO ARE
INVOLVED.
TOMORROW'S GOING TO BE A BIT OF
A DIFFERENT FLAVOR, WE'RE GOING
TO TALK ABOUT MORE OF WHAT
HAPPENS IN THE CLINICAL SPACE SO
NOT ONLY THE CLINICAL TRIAL
ASPECTS OF THINGS BUT ALSO HOW
WE ENGAGE WITH FOUNDATIONS AND
PATIENTS AND WHERE THEY MAY
BE-FUL ALONG THE PATH AND IT WAS
REALLY NICE TO HAVE THAT INITIAL
TALK FROM THE CF FOUNDATION
BECAUSE THEY ARE THE GOLD
STANDARD FOR ALL OF US
FOUNDATIONS FOR WHICH WE'RE ABLE
TO FUNCTION EMPLOY SO I WANT TO
GIVE YOU A BIT OF A FLAVOR FOR
THE TALKS TOMORROW.
WE WILL SPEND SOMETIME IN THE
MORNING LEARNING ABOUT THE
CHALLENGES TO TRIAL DEVELOPMENT
AND INFANTS AND CHILDREN WITH
RARE LUNG DEC.
WE WILL THINK A LITTLE BIT ABOUT
WHAT GOES INTO DESIGNING AND
EXECUTING CLINICAL TRIALS, PIT
FALLS TO,A VOID, THINGS TO MAKE
SURE WE CONSIDER, WE WILL LEARN
A LITTLE BIT FROM THE FIRST
CLINICAL TRIAL IN PEDIATRIC AND
INTERSTITIAL LUNG DEC, WHAT WE
LEARN PRACTICES THAT PROCESS
TALK ABOUT CONTRACTING FOR
INVESTIGATOR INITIATED CLINICAL
TRIALS.
THEN WE WILL HAVE ANOTHER LUNCH
BREAK AS WE DID TODAY AND THEN
IN THE AFTERNOON WE WILL FOCUS
ON SUCCESS STORIES WE HAVE FROM
THIS CLINICAL SIDE OF THINGS,
WE'RE LUCKY TO HAVE AN ADULT
PERSON WITH CF SPEAKS MORE ABOUT
HIS EXPERIENCE WITH CLINICAL
RESEARCH, SO FROM A PATIENT
PERSPECTIVE AND WE WILL LEARN
FROM THE PC D FOUNDATION THEIR
EXPERIENCE WITH CLINICAL TRIALS,
AND WE'LL HEAR ABOUT THE
MEDICATION PIPELINE FOR
PULMONARY FIBROSIS HAS HAD GREAT
STRIDES OVER THE PAST SEVERAL
YEARS AND THEN FINALLY AS A
GREAT EXAMPLE OF HOW THE LAMB
FOUNDATION HAS REALLY HELPED
BRING ABOUT TARGETED THERAPY, IN
THAT PARTNERSHIP, AND THEN
PERHAPS, THE MOST REALLY
EXCITING PART OF THE DAY IS,
BREAK OUT SESSIONS IN THE
AFTERNOON, SO WE'LL HAVE 3
SEPARATE BREAK OUT SESSIONS THAT
-- WITH DIFFERENT MODERATORS,
THAT WILL HOPEFULLY HELP
CONTINUE THE SAME KIND OF
CONVERSATION WE'VE BEEN HAVING
TODAY, SO THAT WE CAN REALLY TRY
TO GET ACTION ITEMS AND IDEAS
ABOUT HOW TO MAKE THIS PROCESS
BETTER.
SO WITH THAT WE JUST HOPE THAT
WE WILL SEE YOUR FACES TOMORROW,
I PROMISE FOR THE BASIC SCIENCE
PEOPLE AND THE RESEARCH PEOPLE,
WE WILL -- IT WILL BE AN
INTERESTING DAY AND THERE'S SOME
PATIENT FACES TO JUST HELP
CONTINUE TO INSPIRE PEOPLE TO DO
THE GOOD WORK YOU GUYS ARE
DOING.
>> ANY OTHER FINAL WORDS, MARRAH
NNO THAT COVER ITS NICELY AND
LOOK FORWARD TO SEEING EVERYBODY
TOMORROW AT THE MEETING.
>> SEE IN THE MORNING GUYS,
THANK YOU.