GOOD MORNING AND WELCOME TO
THE WORKSHOP CONCEPT TO THE
CLINIC, HOW TO ADVANCE
INNOVATIVE LUNG AND SLEEP
THERAPIES TO PATIENTS WITH HIGH
UNMET NEEDS.
FOR THOSE OF YOU WHO ARE JUST
JOINING US TODAY, MY NAME IS
MARRAH LACHOWICZ-SCROGGINS, I'M
THE BRANCH CHIEF FOR LUNG
DEVELOPMENT AND PAID RICK
DEVELOPMENT BRANCH AS WELL AS
ONE OF THE CO-ORGANIZERS OF THIS
WORKSHOP.
WE ARE LOOKING FORWARD TO AN
EXCITING SECOND DAY TOGETHER.
NEXT SLIDE.
>> GOOD MORNING.
THIS PRESENTATION IS BEING
RECORDED.
PLEASE MAINTAIN RESEARCH
INTEGRITY AND CONFIDENTIALITY.
USE CHAT FOR DISCUSSION WITH
OTHER WORKSHOP PARTICIPANTS.
THIS, TOO, WILL BE USED FOR OPEN
DISCUSSION BETWEEN WORKSHOP
PARTICIPANTS.
COMMENTS WILL BE CAPTURED FOR
REVIEW BY WORKSHOP SPONSORS.
USE Q&A TO DIRECT QUESTIONS TO
SPEAKERS.
THIS TOOL CAN BE USED DURING THE
SESSION TO ASK THE SPEAKERS A
QUESTION.
QUESTION WILL BE CAPTURED FOR
REVIEW BY WORKSHOP SPONSORS.
KINDLY STAY ON MUTE AND OFF
CAMERA.
THANK YOU.
>> NEXT N SLIDE, PLEASE.
I WOULD LIKE TO KICK OFF THIS
MEETING WITH A BRIEF WELCOME OF
DR. MATUTE-BELLO WHO IS THE
ACTING DIRECTOR OF LUNG
DISEASES.
>> THANK MARRAH AND I HOPE
EVERYBODY CAN HEAR ME.
GOOD MORNING TO ALL.
I AM REALLY DELIGHTED TO BE HERE
TODAY WITH YOU ON THE SECOND DAY
OF THIS WORKSHOP.
AS WE GATHER HERE TO EXPLORE
EFFECTIVE APPROACHES TO
PERFORMING TRANSLATIONAL
RESEARCH.
THE DIVISIONECOGNIZES THAT
EFFECTIVE TRANSLATION OF IDEAS
FROM THE BENCH INTO THE CLINIC
REQUIRES COLLABORATION BETWEEN
BASIC SCIENTISTS, CLINICIANS AND
INDUSTRY PARTNERS.
DOING THIS EFFECTIVELY REQUIRES
COORDINATION ACROSS DIFFERENT
DISCIPLINES ANDIP INSTITUTIONS
THIS CAN BE PARTICULARLY
CHALLENGING.
WITH THIS ING.MIND, WE HAVE
GATHERED TODAY AN IMPRESSIVE
GROUP OF EXPERTS WHO WILL BE
PROVIDING US WITH AN OVERVIEW ON
HOW TO NAVIGATE THE PATH TO THE
CLINIC WITH EMPHASIS HOW TO TAKE
CLINICAL DATA DESCRIBING
MECHANISMS OF ACTION, SUCH AS
HOW A DRUG OR DEVICE MAY TARGET
SPECIFIC PATH WAYS OR
PHYSIOLOGICAL PROCESS, CLINICAL
DATA SUPPORTING THE PROPOSED
MECHANISM AND EFFICACY.
WE HOPE THIS WORKSHOP WILL
ENCOURAGE THE TYPE OF
INTERDISCIPLINARY COLLABORATION
THAT IS REQUIRED TO TRANSLATE
MORE DISCOVERIES INTO EFFECTIVE
INTERVENTIONS WHO WILL HELP THE
MANY PATIENTS TODAY ARE
SUFFERING FROM LUNG AND SLEEP
DISORDERS.
TODAY WE WILL BE DISCUSSING HOW
BENCH DISCOVERIES CAN ENTER THE
CLINICAL PIPELINE DEVELOPMENT,
EARLY PHASE TESTING, SAFETY,
PRELIMINARY EFFICACY.
DOING THIS SUCCESSFULLYY REQUIRS
LEVERAGE IN PARTNERSHIPS WITH
ACADEMIA, RESEARCH ORGANIZATIONS
AND INDUSTRY COLLABORATORS WHO
SUPPORT THE DEVELOPMENT OF THE
INVESTAL PRODUCT.
AS DISCUSSED YESTERDAY, THIS
PROCESS INCLUDES FUNDING SOURCES
FOR GRANTS THAT HAVE BEEN
SECURED TO ADVANCE RESEARCH,
WHETHER IT BE FROM INVESTORS OR
UNIQUE RESEARCH PROGRAMS SUCH AS
NHLBI -- PROGRAM OR SMALL
BUSINESS PROGRAM.
THIS IS NFICIENT.HER CRITICAL O
SUCCESSFULLY ADVANCE NOVEL
INTERVENTIONS IS TO ENGAGE
PATIENTS AND HEALTH CARE
PROVIDERS IN THE DEVELOPMENT
PROCESS, INCLUDING PATIENT
ADVOCACY GROUPS AND PROFESSIONAL
SOCIETIES.
YOU WILL HEAR MORE HOW HO THIS
SUCCESSFULLY IN TODAY'S AGENDA.
IMPORTANTLY, WE WANT YOU TO NOT
JUST LISTEN, BUT ACTIVELY
PARTICIPATE IN THE BREAKOUT
SESSIONS ESSENTIAL FOR THE
SUCCESS OF THIS WORKSHOP SO WE
CAN TRULY IDENTIFY BARRIERS TO
TRANSLATING SCIENTIFIC FINDINGS
INTO MEDICAL INTERVENTIONS AND
DISCUSS HOW TO OVERCOME THESE
BARRIERS.
FOR EXAMPLE, WE KNOW LUNG
DISEASES OFTEN INVOLVE COMPLEX
PHYSIOLOGICAL PROCESSES.
HOW CAN WE IDENTIFY IODELS TO
ENSURE PATHWAYS OF TARGETS THAT
MAY TREAT AN ARRAY OF LUNG
DISEASES?
WHAT ARE SOME OPTIMAL TRIAL
DESIGNS THAT CONSIDER PATIENT
HETEROGENERALITY AND
STANDARDIZED.
WHAT NEW TOOLS OR BIOMARKERS ARE
SENSITIVE ENOUGH FOR EFFICACY.
CAN WE ACCEPT NEW CLINICAL TRIAL
OUTCOMES BEYOND FEV1
PARTICULARLY RARE DISEASES ASE
ITH ITUNMET NEEDS THAT
CANNOT DR FOR THE SAMPLE SIZES
TO DETECT MEANINGFUL OUTCOMES.
CHALLENGE THAT IS NOT BEING THE
FOCUS OF THIS WORKSHOP, IT IS
HOW TO IMPLEMENT.
WE WANT TO HEAR BARRIERS OF
IMPLEMENTATION, LACK OF
AWARENESS, THE RESISTANCE FOR
CHANGE AND THE NEED FOR TRAINS
AND RESOURCES AND HOW TO
OVERCOME BARRIERS TO TRULY
EFFECTIVELY END UP REACHING THE
PATIENTS WHO NEED THESE NEW
DISCOVERIES THE MOST.
THAT IS MY CHALLENGE FOR YOU
TODAY.
I CHALLENGE ALL OF YOU TODAY TO
LAY THE GROUNDWORK THAT WILL
HELP US BUILD A PATH TOWARDS
CURING AT LEAST ONE C LUNG
DISEASE HOPEFULLY MORE.
GO FOR IT.
THANK YOU VERY MUCH.
IT HAS BEEN A GREATPLEASURE.
>> THANK YOU, GUS.
I WANT TAKE THIS OPPORTUNITY
TO BRIEFLY REINTRODUCE OUR OTHER
CO-ORGANIZERS FOR THE WORKSHOP.
MY COLLEAGUE DR. JOHN SHERIDAN
IS THE BRANCH CHIEF OF THE
RESTRICTIVE AND VASCULAR
DISEASES BRANCH AND CO-LEADING
THIS MEETING.
NEXT SLIDE.
WE ALSO HAVE TWO WONDERFUL
WORKSHOP CO-CHAIRS THAT YOU WILL
BE HEARING FROM THROUGHOUT THE
MEETING TODAY.
WE HAVE DR. KATELYN KRIVCHENIA,
WHO IS THE DIRECTOR OF THE
INTERSTITIAL AND RARE LUNG
DISEASE PROGRAM AS WELL AS THE
DIRECTOR OF THE INFANT CYSTIC
FIBROSIS NEWBORN SCREENING
PROGRAM AT NATIONWIDE CHILDREN'.
SHE CARES FORNFANTS A
CHS WELL ASOUNG ADULTS
WITH LUNG DISEASES.
JEFT MOFFIT IS THE CE-PRESIDENT
DEVELOPMENT AND CARBON
BIOSCIENCES.
HE HAS OVER 15 YEARSOVER BIOTECH
EXPERIENCE AND A BOARD CERTIFIED
TOXICOLOGIST.
HE WORKED IN ALL PHASES OF THE
DEVELOPMENT PROCESS AS WELL AS
ON SEVERAL THERAPEUTIC AREAS
FOCUSING MAINLY ON RARE
DISEASES.
NEXT SLIDE.
A PURPOSE OF THIS WORKSHOP IS TO
HELP EDUCATE THE PULMONARY AND
SLEEP MEDICINE RESEARCH
COMMUNITY HOW WE CAN BRING IDEAS
FROM THE BENCH TO THE CLINIC.
WE WANT TO DISCOVER THE BARRIERS
AND FACILITATORS INNOVATION
FOR DEVELOPING.
THERE IS MISALIGNMENT WITH
DISEASE BURDEN AND NOVEL THERAPY
INNOVATION WHERE IDEAS MAY BE
IMPEDED BY A VARIETY OF
DIFFERENT FACTORS SUCH AS
DECISION MAKING FOR A CLINICAL
MODEL ALL THE WAY TO SECURING
CAPITAL TO SUPPORT DRUG
DEVELOPMENT IN ADVANCE OF AN
IND.
THE SLOW SPEED WE ARE MAKING
THESE NEW THERAPIES COME TO
MARKET CAN CONTRIBUTE TO
INCREASED MORBIDITY AND
MORTALITY AND EXACERB
EXISTING HEALTH
DISPARITIES. REALLY WANT T TRY
THESE EXISTING GAPS BETWEEN
CLINICAL THERAPY
INNOVATION AND
UNMET HEALTH NEEDS IN LUNG AND
SLEEP MEDICINE AS DR.
MATUTE-BELLO SAID TO REDUCE
HEALTH DISPARITIES, IMPROVE
HEALTH OUTCOMES AND LOWER
AL COSTS.
SOME OF THE SPECIFIC BARRIERS WE
ALREADYOGNIZEALENGES
THAT WE HOPE THE PARTICIPANTS
CAN WEIGH IN DURING THE
BREAKOUTS LATER TODAY INCLUDE
UNDERSTANDING WHAT ARE THE
GREATEST CHALLENGES TO OVERCOME
IN DIFFERENT STAGES OF
DEVELOPMENT FOR NEGLECTED
DISEASE AREAS.
AS DR. MATUTE-BELLO MENTIONED
THIS COULD BE FROM BASIC TO
TRANSLATIONAL SCIENCE TO
CLINICAL TRIALS OR EVEN
IMPLEMENTATION SCIENCE.
ALSO CAN WE PARTNER WITH
REGULATORS FOR INNOVATION IN
RARE DISEASE AREAS TO HAVE
FASTER CLINICAL TRIALS IN ORDER
TO DETERMINE EFFECTIVENESS OF
NEW THERAPIES?
ALSO HOW IS PUBLIC INVESTMENT IN
BIOMARKER RESEARCH BEST
LEVERAGED IN THE DEVELOPMENT OF
NOVEL THERAPIES?
AND FINALLY, HOW CAN WE ASSURE
EQUITABLE PATIENT ACCESS TO T
THESE INNOVATIVE THERAPIES THAT
ADDRESS UNMET NEEDS.
NEXT SLIDE.
SO AS I MENTIONED YESTERDAY, TO
FACILITATE THERAPEUTIC
INNOVATION WE ARE HOPING TO
DEMYSTIFY THE PROCESS OF GETTING
YOUR IDEAS FROM THE BENCH
THROUGH THE REGULATORY AND
COMMERCIALIZATION PIPELINES.
THE FOCUS OF THIS WORKSHOP HAS
BEEN PRIMARILY IND ENABLING
PATHWAYS, THE PATH WOULD
TAKE YOUR IDEA THROUGH RELEVANT
SYSTEMS, PK STUDIES AND
AC CAPITAL TO MOVE INTO
MANUFACTURING SO YOU ARE READY
TO MOVE INTO TRIALS.
AS DR. MATUTE-BELLO MENTIONED
YOU NEED TO PARTNER WITH
PATIENTS AS WELL AS OTHER PEERS
SUCCESSFUL IN THIS PROCESS.
YOU'LL SEE THESE WORKSHOPS
CONTINUE TODAY THROUGH THE
WORKSHOP SESSIONS.
NEXT SLIDE.
SO THE SPEAKERS ON TODAY'S
AGENDA WILL BE REALLY FOCUSING
ON HOW TO CONDUCT CLINICAL
TRIALS FOR RARE DISEASES AND HOW
THAT PRESENTS A UNIQUE SET OF
CHALLENGES THAT COMPLICATE THE
PATH TO INNOVATION.
FIRSTLY, WE KNOW THERE ARE SMALL
PATIENT POPULATIONS IN SOME OF
THESE RARE DISEASES MAKING IT
DIFFICULT TO RECRUIT ENOUGH
PARTICIPANTS TO ACHIEVE
STATISTICALLY SIGNIFICANT
RESULTS.TEN THIS MAY LEAD TOD T
WITH LIMITED POWER AND INCREASED
VARIABILITY.
WE KNOW THERE IS A HETEROGENEITY
WHICH CAN FURTHER COMPLICATE
PATIENT SELECTION AND RESULTS
AND INTERPRETATIONS.
THE LACK OF ESTABLISHED END
POINTS AND ESTABLISHED OUTCOME
MEASURES POSES ANOTHER HURDLE
OFTEN NECESSITATING NOVEL
ASSESSMENT TOOLS AND BIOMARKERS
WHICH WE KNOW CAN BE TIME
CONSUMING AND RESOURCE
INTENSETIVE.
REGULATORY REQUIREMENTS THOUGH
ARE BECOMING INCREASINGLY
ACCOMMODATING FOR RARE DISEASES.
STILL PRESENT SIGNIFICANT
CHALLENGES IF THEY MUST STRIKE A
BALANCE BETWEEN EXPEDITED ACCESS
TO POTENTIALLY LIFE SAVING
TREATMENTS ALL THE WHILE STILL
ASSURING SAFETY AND EFFICACY.
FINANCIAL CONSTRAINTS ALSO PLAY
A CRITICAL ROLE AS THE HIGH COST
ASSOCIATED WITH DEVELOPING THESE
THERAPIES FOR SMALL PATIENT
GROUPS LEADS TO LIMITED
INVESTMENT FROM POTENTIAL
PARTNERS.
COLLECTIVELY THESE CHALLENGES
NECESSITATE COLLABORATIVE
EFFORTS AMONG STAKEHOLDERS
INCLUDING PATIENTS, RESEARCHERS,
REGULATORY BODIES, CLINICIANS
AND INDUSTRY TO FOSTER
INNOVATION AND ULTIMATELY
DELIVER EFFECTIVE THERAPIES TO
THOSE IN NEED.
AS DR. MATUTE-BELLO MENTIONED
EARLIER, WE DO REALLY WANT
PARTICIPANTS IN THIS MEETING TO
BE ACTIVE.
WE WILL HAVE THE CHAT OPEN FOR
YOU TO CONNECT TO OTHERS
THROUGHOUT THE WORKSHOP.
ADLY, WE WILL HAVE THE
ZOOM ROOM OPEN TODAY FOR ANOTHER
NETWORKING BREAK AND FINALLY WE
HOPE THAT YOU WILL PARTICIPATE
IN THE BREAKOUT SESSIONS AT THE
END OF THE DAY.
THIS WILL REALLY HELP DETERMINE
THE BARRIERS AND FACILITATORS TO
TRANSLATE SCIENTIFIC FINDINGS
FOR SLEEP MEDICINE AND CIRCADIAN
BIOLOGY TO PATIENTS WHO NEED
THEM MOST.
I WOULD LIKE TO TURN THIS
G OVEO DR. KRIVCHENIA
WITH HER TALK PATH TO THE CLINIC
ROAD MAP.
THANK YOU.
>> THANK YOU, MARRAH AND GOOD
MORNING,AGAIN, TO EVERYONE.
THANK YOU FOR JOINING US TODAY.
I APPRECIATE THE INTRODUCTION.
SO WE'RE GOING TO TALK ABOUT
KIND OF THE OTHER HALF OF THIS
PROCESS.
NEXT SLIDE.
SO WE'VE SEEN A VERSION OF THIS
SLIDE BEFORE YESTERDAY AND
TALKED A LOTBOUT THAT A PRE-IND
PROCESS AND THE GOAL OF THIS
WORKSHOP BEING REALLY HOW TO
HELP
FACILITATE THE ENTIRE
SPECTRUM AS WE WORK THROUGH
DIRECT DEVELOPMENT.
TODAY IS MORE ABOUT THAT
CLINICAL ASSESSMENT OF DIRECT
DEVELOPMENT.
THIS IS THE PART THAT MOST
CLINICIANS HAVE AT LEAST SOME
AWARENESS OF, BUT MAY
UNDERAPPRECIATE THE COMPLEXITIES
OF THAT PATH FROM IND TO NDA.
IT IS LONG, IT IS COMPLICATED,
PARTICULARLY IN THE RARE LUNG
DISEASE SPACE.
NEXT SLIDE.
SO AS WAS SAID, I WORK AS A
PEDIATRIC PULMONOLOGIST.
I TAKE CARE OF KIDS WITH ALL
DISEASE. LUN
MY AREA OF FOCUS ARE INFANTS
WITH CF AND PATIENTS WITH
INTERSTITIAL LUNG DISEASE OR
RARE WEIRD KIND OF LUNG DISEASE.
ANYBODY WHO DOESN'T QUITE HAVE A
SURE ANSWER MAY END UP COMING
THROUGH MY CLINIC.
AND FOR THOSE OF US INSHE ROOM
THAT CARE FOR CHILDREN WITHLD LG
DISEASE AND RARE LUNG DISEASE
UNDERSTAND THERE IS A COMPLETE
LACK OF FDA APPROVED THERAPIES
IN THIS SPACE.
REALLY HIGHLIGHTING THE NEED FOR
WORKSHOPS LIKE THIS.
NEXT SLIDE.
I ALSO AM FORTUNATE TO VOLUNTEER
AS A MEMBER OF THE BOARD OF
DIRECTORS FOR THE CHILDREN'S
INTERSTITIAL AND DIFFUSE LUNG
DISEASE.
THIS WAS STARTED BY A SMALL
GROUP OF PARENTS AND CLINICIAN
RESEARCHERS DEDICATED TO
IMPROVING CARE AND EXPANDING
RESEARCH FOR CHILDREN WITH
INTERSTITIAL LUNG DISEASE.
IT HAS BEEN FASCINATING TO
UNDERSTAND AND LEARN MORE ABOUT
THIS ASPECT OF MEDICINE SO THE
ADVOCACY AND SUPPORT NEEDED TO
COMPLEMENT THE MANAGEMENT IF WE
WANT TO DO THIS WELL.
TODAY YOU WILL HEAR SEVERAL
EXAMPLES OF HOW THAT KIND OF
ADVOCACY AND SUPPORT REALLY CAN
HELP WITH THE RESEARCH
MANAGEMENT OF THIS PROCESS AS
WELL.
NEXT SLIDE.
SO A ALL THE SCIENCE WE
HEARDAR ABOUT YESTERDAY, WHICH S
OOL INAT T
PROJECTS THAT WE'LLHA HEAR
TODAY I WANT TO MAKE SURE WE
HAVE A FACE IN MIND AS WE THINK
ABOUT THE CHILDREN AND PATIENTS
WE ARE HOPING TO HELP.
THIS IS A PICTURE OF M.
SHE AND HER FAMILY GAVE ME
PERMISSION TO SHARE PICTURES AND
HER STORY WITH YOU TO, AGAIN,
HELP HER R THIS PROCESS.
AFTER BIRTH HER LUNGS WERE
FAILING TO OXYGENATE AND
VENTILATE AND SHE NEEDED HELP
WITH A VENTILATOR.
GENETIC TESTING SHOWS TWO --
SHOWING SURFACTANT PROTEIN B
DEFICIENCY.
THIS IS INCREDIBLY RARE DISEASE.
MUTATIONS IN THIS DISEASESE REST
IN DYSFUNCTIONAL SURFACTANT.
YOU CAN SEE THESE DISORGANIZED
BODIES COMPARED TO NORMAL.
THIS LEADS TO BUILD UP OF
MATERIAL IN THE ALVEOLI SPACES.
THERE IS NO WONDER THIS GIRL
COULDN'T BREATHE LOOKING AT THIS
PICTURE ON THE RIGHT.
SO THERE IS NO PROVEN TRE
N THIS ZZ.
THERE MAY BE SOME BENEFIT FROM
HIGH-DOSE STEROIDS AND OTHER
ANTI-INFLAMMATORY MEDICINES, BUT
NONE OF THIS IS PROVEN AS NO
RANDOMIZED CONTROL TRIALS CAN
REALLY BE DONE IN THIS GROUP.
SO AS CLINICIANS WE ARE LEFT TO
OFFER THERAPIESPI THAT MIGHT WO
AND COUNSEL FAMILIES THAT
PROGNOSIS IS POOR.
M'S LIFE HAS BEEN FULL OF
HOSPITALIZATIONS AND CHRONIC
ILLNESS.
SHE HAS ALWAYS BEEN CUTE AS YOU
SEE HERE, BUT LIFE IS NOT EASY.
SHE IS NOW 16.
I HAVE BEEN CARING FOR HER OVER
THE PAST FIVE YEARS.
SHE SPENT MOST OF HER TIME IN
HERIVING ROOM UNABLE TO WALK
ACROSS THEITHOUT 8 TO 10
LITERS SINS OF OXYGEN.
SHE IS THE LUCKY ONE.
MOST CHILDREN DON'T LIVE A YEAR
WITHOUT LUNG TRANSPLANTATION.
HERE ARE A SCANS, THEEGREE OF
DISTORTION AND ORABNORMALITIES E
HAS AS A RESULT OF HER DISEASE.
NEXT SLIDE.
THIS IS HER A COUPLE OF WEEKS
AGO.
SHE IS NOW SIX WEEKS OUT F
HER OWN LUNG TRANSPLANT.
SO THE PICTURE ON THE RIGHT
SHOWS FOR THE FIRST TIME IN HER
LIFE SHE IS ABLE TO WALK WITHOUT
OXYGEN.
AND NOW SHE DOESN'T HAVE A TRACH
ANYMORE.
AS IS THE CASE WITH ORGAN
TRANSPLANT WE HAVE TRADED ONE
DISEASE FOROR LIFE OFIMMUNOSUPP
REJECTION OF THAT LUNG.
SHE IS THE LUCKY ONE, AGAIN,
THIS IS THE GOOD OUTCOME.
THERE IS GOOD RESEARCH BEING
DONE THERE THE PRECLINICAL
SPACE.
LABS ARE EXPLORING TREATMENTS
THAT FACILITATE PROTEIN FOLDING
AND TRAFFICKING, SIMILAR TO
MEDICATIONS FOR CF T R VARIANTS.
THOSE LOOKING AT GENOME EDITING
OR THERAPY.
HOTH DOHO GET THESE THERAPIES TO
INFANTS AT THIS STAGE WHEN THEY
NEED THEM FOR SURVIVAL.
IF MOST DIE BEFORE A YEAR OF
AGE, HOW DO WE GET THESE DRUGS
TO THEM?
THIS IS TRULY AN UNMET NEED N I
THATTRIC SPACE.
NEXT SLIDE.
SO AS WAS DISCUSSED YESTERDAY,
THIS PROCESS IS INTENSE.
THIS IS ANOTHER WAY W OF
VISUALIZING THIS IN TERMS OF
MERE VOLUMES OF DRUGS THAT MAKE
IT THROUGH EACH STEP OF THE
PROCESS.
OF THE THOUSANDS OF TREATMENTS
ENTERING PRECLINICAL TESTING
ONLY HANDFULS MOVE INTO CLINICAL
RESEARCH STAGE.
ONLY ABOUT 14% OF DRUGS ENTERING
CLINICAL TRIALS WILL END UP
BEING APPROVED.
THIS PROCESS IS LONG, IT IS
EXPENSIVE ESTIMATED COSTS
RANGING FROM $314 MILLION TO
$2.8 BILLION FOR DRUG
DEVELOPMENT, THAT IS A SINGLE
DRUG.
ANYTHING THAT CAN HELP SMOOTH
THAT PROCESS SHOULD BE UTILIZED.
WE TALKED ABOUT A LOT OF THOSE
YESTERDAY, RESEARCHERS ARE BEING
SAVVY USING RESOURCESNGVAILABLE
TO TRY TO MOVE THINGS FASTER.
NEXT SLIDE.
TODAY WE ARE GOING TO A LOT
ABOUT HOW PATIENT FOUNDATIONS
AND INTERACTION WITH PATIENTS
MAY HELP MOVE THIS ALONG AS
WELL.
THERE ARE SEVERAL STEPS ALONG
THE WAY WHERE PATIENT
FOUNDATIONS AND ORGANIZATIONS
MAY BE HELPFUL.
CONNECTING RESEARCHERS WITH
CLINICIANS AND PATIENTS.
IN ULTRA RARE DISEASES PATIENTS
ARE FEW AND FAR BETWEEN.
THIS CONNECTION IS IMPORTANT
WHEN IT COMES TO STUDY DESIGN
RECRUITMENT RETENTION TO MAKE
THE CLINICAL RESEARCH PART OF
THINGS MORE SUCCESSFUL.
WHAT OUTCOME MEASURES ARE
ACTUALLY MEANINGFUL TO THEL
PATIENTS ANDPA FAMILIES?ESTUDY
PROTOCOLS ARE REASONABLE FOR
PATIENTS AND FAMILIES TO AGREE
TO ENROLL?
AND THEN HOW ARE WE GOING TO BE
ABLE TO GET THEM TO STICK IT OUT
THROUGH THE DURATION OF THE
STUDY?
ONCE THERE ARE RESULTS PATIENT
ORGANIZATIONS CERTAINLY CAN HELP
DISSEMINATE THEM AND ADVOCACY
HERE ENCOMPASSES NOT ONLY
ADDRESSES PATIENTS AND FAMILY
NEEDS IN THEIR EVERYDAY LIFE,
BUT ADVOCACY REGOC POLICY
DECISIONS IMPACTING RARE DISEASE
RESEARCH.
DEPENDING ON TG FOUNDATION,
FUNDING CAN BE PROVIDED AT PD D.
NEXT SLIDE.
NOT ALL FOUNDATIONS ARE EQUAL.
CERTAINLY ONE OF THE MOST
SUCCESSFUL IS THE CF FOUNDATION.
WE HAD A NICE OVERVIEW YESTERDAY
OF THEIR APPROACH SUPPORTING THE
DRUG PIPELINE.
THEY HAVE FUNDING OF EARLY E STE
BIOTECH COMPANIES TO DEVELOP
BREAK THROUGH TREATMENTS.
A ROBUST FUND-RAISING CAPABLE IN
ORDER TO FUND RESEARCH
INITIATIVES BROADLY.
COLLABORATE WELL WITH
PATIENTS,ICALLY NATIONS AND
RESEARCHERS AND HAVE A
COMMITMENT TO ADVOCACY.
SOME ORGANIZATIONS, PARTICULARLY
THOSE THAT MAY BE YOUNGER HAVE
MORE OF A FOCUS ON PATIENT
FAMILY EDUCATION AND SUPPORT.
THEY MAY NOT HAVE THE FUNDING
APPARATUS FOR WIDESPREAD FUNDING
OR RESEARCH.
NEXT SLIDE.
AS YOU START EXPLORING THE
VARIOUS PATIENT FOUNDATIONS OUT
THERE UNDERSTANDING THERE ARE
AREAS OF OVERLAP.
THE FOUNDATION I WORK WITH
SERVES PATIENTS WITH
INTERSTITIAL LUNG DISEASE, BUT
MANY, MANY DIAGNOSES UNDERNEATH
THAT UMBRELLA.
EACH OF THOSE DISORDERS CAN HAVE
POTENTIALLY THEIR OWN
FOUNDATION.
THENEHI RESEARCH FOUNDATION,
COPA SYNDROME FOUNDATION, TBX4
LIFE, PAP DATION.
AMONG THESE YOU HAVENT
POTENTIAL SKILL SETS OR AREAS
THAT CAN HELP FOSTER DIFFERENT
ASPECTS OF THE RESEARCH PROCESS.
SO WORKING WITH THE PATIENT
FOUNDATION OUTSIDE OF THE CS
SPACE IS LIKELY NOT JUST WORKING
WITH ONE.
NEXT SLIDE.
WE TALKED A LITTLE BIT ABOUT HOW
THEY CAN IMPACT MULTIPLE SPOTS
ROCESS OF DRUG
DEVELOPMENT.
AND ONE THING I FAILE TO
MENTION IS THE IMPORTANCE OF
NATURAL HISTORYRY STUDIES AND
UNDERSTAND NATURAL HISTORY OF
DISEASE SOO RESEARCHERS CAN
DESIGN STUDIES WITH APPROPRIATE
END POINTS AND TREATMENT
OUTCOMES.
AGAIN, THE IMPORTANCE OF STUDY
RECRUITMENT AND DESIGN AND
FINALLY DISTRIBUTING RESULTS AND
THEN ALSO THAT POST MARKETING
SURVEILLANCE.
SO PATIENT FOUNDATIONS WILL HAVE
CONNECTIONS WITH FAMILIES ON
THESE MEDICATIONS AND HAVING
MAYBE SIDE EFFECTS OR
EXPERIENCING THINGS POST
MARKETING THAT WILL BE IMPORTANT
AS A COMMUNITY TO UNDERSTAND.
NEXT SLIDE.
SO WE HAVE A NUMBER OF WONDERFUL
SPEAKERS TODAY WHO WILL BE
TOUCHING ON SEVERAL ASPECTS OF
THIS POST IND PHASE OF THE
PROCESS.
WE'LL SPEND TIME LEARNING ABOUT
CHALLENGES TO TRIAL DEVELOPMENT
IN INFANTS AND CHILDREN WITH
RARE LUNG DISEASE.
WE'LL THINK ABOUT HOW TO DESIGN
AND EXECUTE CLINICAL TRIALS,
LEARN FROM THE FIRST CLINICAL
TRIAL IN THE PEDIATRIC
INTERSTITIAL LUNG SPACE, TALK
ABOUT CONTRACTING FOR CLINICAL
STUDIES.
AND IN THE AFTERNOON SUCCESS
STORIES IN THE CLINICAL SPACE.
WE HAVE AN ADULT PERSON WITH CF
SPEAKING ABOUT HIS EXPERIENCE.
WE WILL LEARN ABOUT PCDFOWLKES,
FROM THEM, THEIR EXPERIENCE WITH
OF THE MEDICATIONS FOR PULMONARY
FIBROSIS THAT HAVE BEEN ROBUST
OVER THE PAST FEW YEARS AND
FINALLY LEARN HOW THE LAND
FUNCTION HAS BRUNG ABOUT TARGET
LUNG RESEARCH IN THEIRRC SPACE.
MORNING.
WE WILL BE USING THE Q&A TOOL IN
THE BOTTOM TO ASK QUESTIONS OF
THE PANELISTS.
SO PLEASE KEEP THAT IN MIND AS
QUESTIONS COME TO YOU.
SO WE'LL START WITH OUR SESSION
4, NAVIGATING CLINICAL TRIALS.
AND I GET TO TALK DURING THIS
ONE, TOO.
IF I COULD HAVE THE SPEAKERS POP
THEIR CAMERAS ON SO WE CAN SEE
YOUR FACES.
NEXT SLIDE.
I AM LUCKY TO BE ABLE TO
MODERATE WITH DR. ROBIN
DETERD
DETERDING.
SHE HAS DEDICATED HER RESEARCH
AND CLINICAL CAREER TO CHILDREN
WITH COMPLEX AND RARE LUNG
DISEASE.
FOUNDER OF THE CHILDREN'S
INTERSTITIAL AND DIFFUSE
RESEARCH NETWORK AND A
RECOGNIZED EXPERT IN THE FIELD
OF CHILD.
HEY, ROBIN.
JOINING US THE BEACH, IT
SEEMS.
SO WE'LL GO NEXT SLIDE.
GREAT.
SO OUR OTHER SPEAKERS, ROBIN
GETS, DR. DEET DETERDING.
DR. JENNIFER WAMBACH IEN A
NEONATOLOGIST.
PART OF PEDIATRIC LUNG
TRANSPLANT AND SHE FOCUSES ON
UNDERSTANDING OF INTERSTITIAL
LUNG ZZ AND DEVELOPING
THERAPIES.
DORIS SANCHEZ BRINGS OVER 25
YEARS OF INDUSTRY EXPERIENCE IN
RARE DISEASE AND ONCOLOGY
INDICATIONS.E FOUNDED CLINDEV SI
DR. DETERDING WILL TALK ABOUT
TRIAL AND KAREN SCHNEIDER IS A
BLUEPRINT ATTORNEY AND HELP US
TO THINK ABOUT INVESTIGATOR
INITIATED STUDIES.
I WILL TURN IT OVER TO DR.
WAMBACH.
IF YOU HAVE QUESTIONS, PUT IT IN
THE Q&A TOOL AND WE WILL HAVE
TIME TO TALK WITH OUR PANELISTS
IN THE Q&A DISCUSSION.
>> I'M A NEONATOLOGIST AND TAKE
CARE OF BABIES AND PART OF THE
THE PEDIATRIC LUNG TRANSPLANT
PROGRAM.
I'M TALKING TODAY ABOUT SOME
CLINICAL TRIAL PERSPECTIVES FOR
ENROLLING INFANTS ANDREN
WITH RARE LUNG DISEASES.
NEXT SLIDE.
I HAVE NO RELEVANT DISCLOSURES.
NEXT SLIDE.
SO I'M GOING TO START FIRST WITH
A PATIENT CASE AND THIS IS A
PHONE CALL OR E-MAIL I GET
APPROXIMATELY ONCE A MONTH.
SO THIS WAS A BABY WHO WAS BORN
AT TERM SO 37 WEEKS GESTATION.
SHE IS NOW SIX WEEKS OLD AND HER
CHEST X-RAY IS PICTURED HERE TO
THE RIGHT.
I WAS CONTACTED BECAUSE THIS
BABY HAD SEVERE RESPIRATORY
FAILURE.
BEFORE BIRTH THERE WERE A FEW
HINTS THERE MAY BE ABNORMALITIES
WITH THIS PREGNANCY AND HOW THIS
PREGNANCY WAS DEVELOPING AND THE
TEAM WAS SUSPECTING DUODENAL
ATRESIA.
THE INFANT DEVELOPED RESPIRATORY
ARREST AND PLACED ON CPAP AND
INTUBATED FOR REPAIR OF THE
DUODENAL ATRESIA.
THE INFANT ACUTELY WORSENED AND
HAD SEVERE PULMONARY
HYPERTENSION AND WAS ON ECMO FOR
APPROXIMATELY A WEEK.
NEXT SLIDE.
SO THIS INFANT REMAINS INTUBATED
ON MODERATE VENT LAY TOFR
SETTINGS AT SIXSE WEEKS OF AGE
WITH A SUBSTANTIAL OXYGEN O
REQUIREMENT,ENT
PULMONARY HYPERTENSION, NEAR
SYSTEMIC R.V. PRESSURE AND BEEN
ON MANY VASODILATORS.
GENETIC TESTING WAS SENT SEVERAL
WEEKS AGO WHICH IS STILL
PENDING.
GIVEN THE SEVERITY, THE TEAM
SEND GENOMEEQUENCES RESULTING
IN DENOVO VARIANT IN FOXF1
DISEASE, WHICH MATCHES THIS
PATIENT'S CLINICAL COURSE.
NEXT SLIDE.
SO THE QUESTION FROM THIS
REFERRING POSITIONGS ARE THERE
ANY THERAPIES TO HELP THIS
INFANT?
SO THIS IS JUST A BRIEF OUTLINE
OF MY PRESENTATION TODAY.
I'M GOING TO FOCUS ON AWARENESS
AND RECOGNITION OF THESE RARE
DISORDERS AMONG INFANTS AND
CHILDREN, DIADR APPROACHES
TO IDENTIFYING THE IDEOLOGY FOR
RESPIRATORY FAILURE
N INFANTS
AND CHILDREN.
CURRENTLY AVAILABLECU THERAPIES
WHICH KATELYN MENTIONED ARE
EMPERIC IN LUNG TRANSPLANTATION.
HOW DO WE BRING TRANSLATIONAL
DISCOVERIES THAT ARE EXCITING TO
AFFECTED INFANTS THROUGHOUT
UNITED STATES?
PICTURED HERE, THIS IS A SLIDE
COURTESY OF LARRY NOGEE AND
IDENTIFIED GENES ON THIS SLIDE.
ON THE KPX AX SITUATION YOU SEE
THE AGE OF ON SET AND THE Y AXIS
PRIMARY PHENOTYPES.
THERE HAVE BEEN MARKED ADVANCES
OF LUNG DISEASES IN INFANTS,
CHILDREN AND ADULTS.
THE PHENOTYPES HAVE SOME OVERLAP
LISTED ON THE Y AXIS.
SOME INFANTS ARE PRESENTING WITH
SEVERE DIFFUSE LUNG DIAGNOSE AND
PROGRESSIVE FIBROSIS, OTHERS
HAVE GROWTH ABNORMALITIES AND
OTHERING PRESENTING WITH
PULMONARY HYPERTENSION OR
INFECTIOUS OR IMMUNE PHENOTYPES.
FOR THE PURPOSES OF DISCUSSION
TODAY WE ARE GOING TO FOCUS ON
THESE FOUR GENES AS THESE
INFANTS WITH PATHOGENIC VARNTSS
IN THESE GENES HAVE SEVERE
RESPIRATORY FAILURE AND THERE
ARE PRECLINICAL STUDIES THAT ARE
EXCITING AND ENCOURAGING THAT
POTENTIALLY COULD DEVELOP
THERAPIES FOR THESE INFANTS.
SO AGAIN BACK TO THE AWARENESS
AND RECOGNITION OF THESE
DISORDERS.
SO T
MOST COMMON CAUSES OF
RESPIRATORY FAILURE, GENETIC
RESPIRATORY FAILURE IN TERM
INFANTS ARE GENETIC DISORDERS
ARE SURFACTANT, VARIANTS, ABCA3
DEFICIENCY AND NKX 2RKS-1.
THESE ARE IMPORTANT FOR
METABOLISM IN THE TYPE 2 CELL.
SF PROTEIN B AND KR.
ABCA3 SIT ON THE BODIES THAT
KATELYN DESCRIBED ON THE IMAGE
FROM HER PATIENT.
AND ABCA3 COMBINE TO MAKE
SURFACTANT.
THE TRANSCRIPTION FACTOR IS
IMPORTANT FOR LUNG DEVELOPMENT
BUT ALSO FOR DEVELOPMENT OF THE
THYROID AND BRAIN.
THE PATIENT DESCR IN MY
VIGNETTE AT ACDMPC.
THIS IS DUE TO PATHOGENIC
VARIANTS IN FOX F1 THAT
INCORPORATE THE GENE OR UPSTREAM
REGULATORY REGIONS.
WITH INCREASED USE OF GENE
SEQUENCING WE ARE IDENTIFIES
OTHER CAUSES OF SEVERE LUNG
INFANT AND CHI
AND MANY DISORDERS HAVE
ABNORMALITIES.
WHETHER COPA OR STING OR
MULTIORGAN SYSTEM INVOLVEMENT.YS
SO WHEN TO SUSPECT THESE
DISORDERS?
A TERM INFANT WITH PERSISTENT
RESPIRATORY FAILURE MORE THAN
SEVEN DAYS SHOULD INITIATE
CONCERN FOR A RARE GENETIC
CONDITION AFFECTING LUNG
DEVELOPMENT AND LUNG FUNCTION.
CERTAINLY WE KNOW THERE ARE RISK
FACTORS FOR TERM BABIES TO HAVE
BREATHING PROBLEMS AFTER BIRTH,
INCLUDING 37 WEEKS VERSUS 40
WEEKS.
THERE IS A RANGE OF BEING
CONSIDERED TERM AND THOSE IN THE
EARLIER SPECTRUM CAN HAVE
RESPIRATORY DISTRESS THAT
IMPROVING IN THE FIRST WEEK OF
LIFE.
INFANTS BORN TO WOMEN WHO HAVEE
DIE BEES, MALE SEX, DESCENT.
ALL OF THOSE ARE RISK FACTORS
FOR RESPIRATORY DISTRESS IN THE
FIRST FEW DAYS OF LIFE THAT
TYPICALLY SHOULD IMPROVE BY THE
END OF THE FIRST WEEK.
IF AN INFANT PRESENTS WITHOUT
THOSE RISK FACTORS IT SHOULD
FLAG THE ATTENTION TO SUSPECT AN
UNDERLYING CONDITION.
IF THERE IS A POSITIVE FAMILY
HISTORY MANY DISORDERS ARE
AUTOSORKS SOMAL RECESSSIVE.
THERE ARE LIMITED PRENATAL
FINDINGS WITH THE EXCEPTION OF
ACDMPV.
SO SOMETIMES FETUSES WILL BE
IDENTIFIED WITH ABNORMALITIES IN
THESE ORGAN SYSTEMS PROMPTINGMS
PRENATAL GENETIC TESTIN
FOR THE GENETIC SURFACCTANT
DISORD TLERS ARE NO OTHERER ENO.
IN KH2-1 IS IMPORTANT FOR LUNG
DEVELOPMENT AND THE THYROID AND
THE SPRAIN AND OTHER PHENOTYPES
MAY BE PRESENT IN THE INFANT WHO
HAS A PATHOGENIC VARIANT IN
NKX2-1.
PART OF THE CHALLENGE IS THESE
ARE VERY RARE CONDITIONS.
MOST NEONATOLOGISTS WILL SEE ONE
OR TWO OF THESE BABIES IN THE
SPAN OF THEIR CAREER.
SURFACTANT PROSTEEN D DEFICIENCD
IS RARE.
THIS IS ANYWHERE FROM 1 TO 4
INFANTS TOTAL IN THE UNITED
STATES BORN WITH SPV.
LOOKING AT THE FREE KWENS OF LOS
OF VARIANCE IN NOMAD A LARGE
DATA BASE FROM APPROXIMATELY
800,000 ADULT INDIVIDUALS, IF
YOU LOOK AT THE LOSS OFION
VARIANTS AND THE KNOWNWN
PATHOGENIC VAMPBTS WE ESTIMATE
DISEASE INCIDENCE OF TO 45,000
BIRTHS.
SO ABOUT 100 INFANTS PER YEAR.
THIS IS CERTAINLY AN
UNDERESTIMATE AS MOST OF THE
VARIANTS THAT RESULT IN ABCA3
DEFICIENCY ARE PRIVATE AND
UNIQUE TO INDIVIDUALS AND
FAMILIES AND
OUR ABILITY TO
PREDICT IS MORE LIMITED.
AND IT IS REALLY DIFFICULT TO
ESTIMATE THE INCIDENCE OF
ALVEOLAR CAPILLARY.
WE SEE PEN ATLANTAS AMONG
FAMILIES WITH THE SAME
PATHOGENIC VARIANT THERE CAN BE
DIFFERENCES IN AGE OF
PRESENTATION AND SEVERITY OF
DISEASE AND PROGRESSION.
NEXT SLIDE.
ISOS REALLYOSIS
MADE WITH GENETIC TESTING AND
TREE OWGS IS PREFERRED OVER
PANEL TESTING.
TREE OWHOLE GENOME SEQUENCE
GIVES US COPY NUMBER VARIANCE
IMPORTANT TO RARE GENETIC LUNG
DISEASES.
THE TURN AROUND TIME IS MUCH
SHORTER.
RIGHT NOW WGS INITIAL RESULTS
ARE BACK IN SEVEN DAYS AND THE
FINAL REPORT IS 14 DAYS AND I
EXPECT THAT THIS WILL SHORTEN
WITHWITIME.
AND TREE E GENOME
SEQUENCINGEN GIVES US THE ABILI
TONTIFY DENOVO VARIANTS NNT
PRESENT IN THE PARENTS AND PHASE
VARIANTS.
THIS IS IMPORTANT FOR ABCA3 AS
WE HAVE FOUND THEM OCCUR ON
CYSTS.
IF THERE ARE TWOABCA3 VARIANTS
IDENTIFIED IT IS IMPORTANT I TO
HAVE THE PARENTAL SAMPLES TO
DETERMINE IF ONE OR BOTH ALLELES
ARE AFFECTED.
IN THE NICU THERE ARE TRIALS IN
FOR CL ILL INFANTS.
I HAVE A COUPLE OF STUDIES
LISTED TO THE RIGH
TI FOR A BABY
IN THE NICU SUSPECTED OF HAVING
A GENETIC CONDITION IS ABOUT 30%
TO 35%.
NEXT SLIDE.
HOWEVER, WE HAVE CONSIDERABLE
VARIATION IN THE AVAILABILITY OF
GENETIC TESTING BY DIFFERENT
NICUs.
THIS IS A STUDY DON'T LOOKING AT
SERVICE AND MULTIPLE LEVEL
4NICUs THROUGHOUT THE UNITED
STATES.
THERE IS VARIABILITY OF
GENETICISTS, GENETIC COUNSELING
SE THE APPROVAL
PROCESS FOR GENOME SEQUENCING.
LUNG BIOPSY, WE ARE ASKED IF
THIS IS NECESSARY FOR THESE
INFANTS AND IF A PATHOGENIC
VARIANT IS IDENTIFIED WITH ME
SEQUENCING, GENOME SEQUENCES OR
WITH THE CLINICAL COURSE THIS
CAN BE DIAGNOSTIC AND THE CHILD
DOES NOT NECESSARILY NEED A LUNG
BIOPSY.
THERE ARE SITUATIONS WHERE A
LUNG BIOPSY IS HELPFUL.
THIS COULD HAPPEN WHEN THE OTHER
RESULTS ARE NONDIAGNOSTIC.
VARIANTS ARE IDENTIFIED, THE
CHILD AS AN ATYPICAL COURSE AND
TO EXCLUDE OTHERDISORDERS THAT
MAY IMPROVE WITH TIME, PODIUM
NOIR INTERSTITIAL GLYCOGENOS
SIXTH.
THERE IS AIR LEAGUE OR HEMO
THORAX.
IT CAN EXACERBATE PULMONARY
HYPERTENSION.
THE LUNG BIOPSY IS VERY HELPFUL,
THERE TR A LOT OF ORR LAPPING
HISTOLOGIC FEATURES.
PICTURED ON THE BOTTOM LEFT LUNG
BIOPSY RESULTS IMAGES FROM
INFANTS WITH DEFICIENCIES AND.
AND YOU CAN SEE THAT MANY OF
THESE DISORDERS HAVE TYPE TWO
CELL HYPERPLASIA.
SO WHILE THESE LUNG BIOPSIES MAY
BE HELPFUL POINTING US IN
SURFACTANT THEY DON'T
DISTINGUISH WITH THE IDEOLOGIES.
ABCA3 DEFICIENCY THERE ARE
CHARACTERISTIC CHANGES IN THE
STRUCTURE.
IF A LUNG BIOPSY IS OBTAINED WE
HIGHLY ENCOURAGEENNI
ELECTROMICROSCOPY THAT CAN BE
HELPFUL IN THE DIAGNOSIS.
I WILL HIGHLIGHT AN ARTICLE
PUBLISHED BY THE GROUP FRO
TORONTO WHO DESCRIBE MORTALITY
OF PEDIATRIC SURGICAL LUNG
BIOPSIES.
THIS WAS A GREAT DESCRIPTION OF
ALL OF THE SERIES ASSOCIATED
MORBIDITIES WITH LUNG BIOPSY.
NEXT SLIDE.
SO IT IS VERY IMPORTANT AS WE
THINK ABOUT CURRENT THERAPIES TO
UNDERSTAND THE GENE TYPE
PHENOTYPE CORRELATION.
THERE ARE SOME DISORDERS THAT
ARE LETHAL WITHIN THE FIRST FEW
MONTHS OF LIFE WITHOUT LUNG
TRANSPLANTATION.
WE THINK SURFACTANT PROTEIN B
DEFICIENT.
THIS IS THE MOST COMMON IDEOLOGY
OF THE DEFICIENCY.
WE
OCCASIONAL LONG-TERM LSURVIVOR
DESCRIBED.
THESE INDIVIDUALS TYPICALLY HAVE
ONE VARIANT THAT PERMITS SOME
AMOUNT OF SURFACTANT PROTEIN B
FUNCTION.
SOME DIE WITHIN THE FEW FEW
MONTHS OF LIFE WITHOUT LUNG
TRANSPLANTATION.
AL B VEOLAR -- SHORTLY AFTER
BIRTH AND DEATH WITHIN THE FIRST
FEW MONTHS OF LIFE WITHOUT LUNG
TRANSPLANTATION.
WE HAVE INCREASED OUR USE OF
GENETIC TESTING AMONG CHILDREN
WITH INTERSTITIAL LUNG DISEASE,
WE HAVE FOUND SOME OLDER INFANTS
AND CHILDREN WHO HAVE PATHOGE
IC VARIANTS IN FOX F1 WHO HAVE
BEEN ABLE TO SURVIVE.
IT SEEMS THOSE INDIVIDUALS HAVE
PATCHY INVOLVEMENT OF DISEASE
THROUGHOUT THEIR LUNGS AND THE
REASONS ARE NOT ENTIRELY CLEAR.
SO IN TALKING ABOUT THOSE WHO
HAVE PRETTY CLEVE CUT GENE TYPE
PHENOTYPE CORRELATIONS, THERE
ARE THOSE WITH MORE VARIABLE
VARIANTS.
THOSE WITH ABCA3 DEFICIENCY
AND -- SOME DELETIONS THAT MAY
PERMIT SOME AMOUNTOM OF FUNCTIO.
THESE FAMILIES ARE MORE
DIFFICULT TO COUNCIL INOU TERMSF
THE DISEASE PROGRESSION AND
PREDICTION FOR SURVIVAL.
AND, AGAIN, CERTAINLY WE ARE
IDENTIFYING OTHER INDIVIDUALS
WHO HAVE MONOGENIC CAUF
LUAUEASE IN INFANTS AND
CHILDREN.
THESE ARE OFTEN ULTRA RARE
DISORDERS AND WE KNOW LESS ABOUT
THE NATURAL HISTORY OF THESE
DISORDERS WE NEED TO FOLLOW
THESE INFANTS AND CHILDREN OVER
TIME.
NEXT SLIDE.
SO OUR CURRENT THERAPIES,
MEDICAL THERAPIES ARE QUITE
LIMITED.
THEY REALLY INCLUDE
ANTI-INFLAMMATORY MEDICATIONS
GIVEN EM P TO CHILDREN
WITH INTERSTITIAL LUNG DISEASES.
TRANSPLANT IS THE DEFINITIVE
TREATMENT OPTION FOR PROGRESSIVE
RESPIRATORY FAILURE.
PICTURED HERE ARE FIVE-YEAR
SURVIVAL RATES FOR INFANTS AND
CHILDREN.
ON THE KPX AXIS IS TIME IN
MONTHS AFTER TRANSPLANT, Y IS
SURVIVAL PROBABILITY.
FOR INFANTS FIVE YEAR SURVIVAL
IS 60%, FOR CHILDREN 80%.
THESE OUTCOMES HAVE BEEN
RELATIVELY STABLE, MAYBE
SOMEWHAT IMPROVED OVER THE PAST
THREE DEKCADES.
INFANTS ARE VERY HILL AT TIME OF
TRANSPLANT, HIGH RISK FOR
DEVELOPMENTAL DELAYS, HEARING
LOSS, NAL
SUPPLEMENTATION AND NDBRONCHULIS
IS A MAJOR MORBIDITY O A
SLIGHTLY LOWER RISK IN INFANTS
MAYBE TAKING ADVANTAGE OF THEIR
NAIVE IMMUNE SYSTEM.
NEXT SLIDE.
SO HOW TO DRINK THESE
TRANSLATIONAL DISCOVERYS TO
INFANTS.
CHALLENGES.
INFANTS OFTEN IDENTIFIED AT 4 TO
6 WEEKS OF AGE, EXPOSED TO
MECHANICAL VENTILATION AND HAVE
INJURE TO T NGS.
THEY ARE PRESENT AT CENTERS
THROUGHOUT THE UNITED STATES, .
THEY ARE CRITICALLY ILL AND DO
NOT DO A GOOD JOB -- PRETERM
INFANTS ARE MORE LIKELY TO HAVE
RESPIRATORY DISTRESS DUE TO
DEVELOPMENTALCIENT SI OFI
SURFACTANT PRODUCTION.
AND THINKING ABOUT BRINGING
THERAPIES WHICH
INFANTS AND
CHILDREN SHOULD WE TARGET?
SHOULD WE TARGET THOSE WITH THE
MOST SEVERE PHENOTYPES UNLIKELY
TO SURVIVE WITHOUT LUNG
TRANSPLANTATION OR CHILDREN WITH
INTERSTITIAL LUNG DISEASE AND
MORE CHRONIC LUNG DISEASE?
THAT IS AN IMPOR
CONSIDERATION ASIO WE THINK ABO
THESE THERAPIES.
CERTAINLY ANY THERAPY WE HAVE
HAS TO HAVE OUTCOMES AT LEAST AS
GOOD OF LUNG TRANSPLANTATION.
AT WHAT POINT WOULD THE FAMILY
CHOOSE.
THE IRBROVAL IS IMPORTANT TO
CONSIDER AS THESE INFANTS WILL
BE AT LIKELY MULTIPLE CENTERS
THROUGHOUT THE UNITED STATES AND
HOW DO WE MEASURE CLINICAL
RESPONSE.
WE HAVE PF Ts FOR OLDER
CHILDREN, FOR INFANTS HAVE
FARE MEASURES TO MEASURE
CLINICAL RESPONSE.
THIS WOULD INCLUDE OXYGEN ATION
AND IMAGING FINDINGS THAT MAY
CHANGE.
I KNOW SEVERAL OTHER SPEAKERS
HAVE TALKED ABOUT N-OF-1
STUDIES.
THE RARENESS OF THESE DISORDERS
PROVIDES UNIQUE CHALLENGES FOR
TRIAL DESIGN.
THESE ARE IMPORTANT
CONSIDERATIONS.
I WILL HIGHLIGHT THIS ARTICLE
THAT WAS RECENTLY PUBLISHED WITH
A NICE APPROACH TO N-OF-1
TRIALS.
CONSIDERATIONS.
WE NEED INCREASED PROVIDER
EDUCATION FOR EARLIER IDENT
IDENTIFICATION AND INCREASED
ACCESSIBILITY TO WGS IN THE NICU
AND PEDIATRIC PULMONARY CLINICS.
MY RECOMMENDATION IS THEY ARE
TRANSPORTED TO CENTERS WHO HAVE
EXPERTISE WITH CHILD AND
TRANSPORT TEAMS.
I WANT TO ALSO SAY IDENTIFYING
INVESTIGATIONAL THERAPIES ONCE
AVAILABLE.
NEXT SLIDE.
AND THEN I THINK IT IS
INCREDIBLY IMPORTANT TO ENGAGE
THE PARENTS OF AFFECTED INFANTS
AND CHILDREN AND CERTAINLY THE
CHILD FOUNS HAS HELPED WITH
THIS.
I THINK WE NEED TO TALK TO THE
PARENTS OF INFANTS WHO WERE E
LANTED VERSUS FAMILIES WHO
PURSUED COMFORT CARE.
IN TALKING WITH FAMILIES ABOUT
TRANSPLANTATION ONCE THEY
HEAR ALL OF THE PROCEDURES AND
MAINTENANCE THAT IS INVOLVED AND
THE FIVE-YEAR SURVIVAL RATES,
HALF OF FAMILIES DO NOT A WANT
TO PURSUE TRANSPLANTATION FOR
THEIR CHILD.
ARE THESE FAMILIES WHO MAY
PURSUE INVESTIGATIONAL THERAPY?
WHAT ARE ETHICS AND CONSENT
ISSUES INVOLVED IN THAT PROCESOC
CERTAINLY IRB APPROVAL TAKES A
WHILE.
REG CENTERS
ALREADY READY TO HAVE AN
INVESTIGATIONAL THERAPY APPROVED
THROUGH THEIR IRB SO ONCE THESE
INFANTS ARE IDENTIFIED AND
ARRI AT CENTERS COULD
RECEIVE EXPEDITIOUS TREATMENT.
WE NEED TO THINK ABOUT CLINICAL
RESPONSE.
AS I MENTIONED, INFANTS, WE HAVE
LIMITED MEASURES OTHER THAN
VENTILATION, OXYGENATION STATUS.
WE NEED TO FOCUS ON BIOMARKERS.
MAYBE CHANGES IN IMAGING CAN BE
AN END POINT.
NEXT SLIDE.
WITH THAT I JUST WANT TO THANK
OUR TRANSPLANT TEAM AT ST. LOUIS
CHILDREN'S HOSPITAL.
OUR RESEARCH TEAM AND
COLLABORATORS ACROSS THE
COUNTRY.
THANK YOU.
>> THANK YOU SO MUCH, DR.
WAMBACH.
THAT WAS GREAT AND CERTAINLY
QUITE A TO-DO LIST, REALLY, IN
TERMS OF CONSIDERATIONS AND
THINGS TO TRY TO IMPROVE THIS
PROCESS.
SO WE'LL MOVE ON TO DORIS
SANCHEZ, OUR NEXT SPEAKER.
AND SO DORIS GO AHEAD AND TAKE
IT AWAY.
>> I'M ON MUTE.
I'M SORRY.
HELLO, EVERYONE.
MOST OF WHAT I'M COVERING TODAY
HAS BEEN PREN ONE FORM
OR ANOTHER DURING THIS WORKSHOP,
BUT IN GREAT DETAIL AS
INDIVIDUAL FOCUSED TOPICS.
THE REALITY IS OPTIMAL
EXECUTION OF CLINICAL TRIALSNI
NOT DONE IN A VACUUM, BUTCUER
A NUMBER OF BROADER ACTIVITIES
OCCUR TO INFORM A SOLL LIED
TRIAL DESIGN AND PROACTIVE TRIAL
EXECUTION.
I WILL BRING MANY O THE FOCUSED
TOPICS THAT HAVE BEEN D,
NOT IN DETAIL, THAT HAS BEEN
DONE, BUT A BROADER PERSPECTIVE
IN THE CONTEXT OF THE
CONSIDERATIONS OF DESIGNING AND
EXECUTING CLINICAL TRIALS.
SO THIS TOPIC CAN GO MANY WAYS.
I'M GOING TO FOCUS ON THREE
PRACTICAL ONES THAT I OFTEN WORK
ON WITH MY CLIENTS WORKING ON
RARE DISEASE IN ONCOLOGY, RARE
INDICATIONS.
THE FIRST ONE I'M GOING TO FOCUS
ON IS THE CLINICAL DEVELOPMENT
STRATEGYELEL WHICH IS BASICALLYR
BRAINSTORMING, RESEARCHING AND
SOLIDIFYING THOUGHTS TO BUILD
OVERALL STRATEGY.
THE NEXT IS CONSIDERATIONS THAT
HELP DEVELOPING A SOLID
CLINICAL TRIAL DESIGN AND THE
LAST IS CLINICAL TRIAL
EXECUTION.
NEXT SLIEX
SO YOUR CLINICAL DEVELOPMENT
STRATEGY.
I KIND OF PUT THAT IN THE
FOREFRONT BECAUSE THAT IS WHERE
YOU ARE ABLE TO DEFINE YOUR
OVERALL GOALS AND STRATEGY FOR A
PROGRAM.
THAT IS REALLY CRITICAL.
KIND OF LIKE IF YOU WANT TO
BUILD A HOUSE.
THIS IS WHERE YOU DETERMINE
WHERE YOU WANT TO BUILD, WHAT IS
YOUR BUDGET, WHAT TYPE OF HOUSE
DO YOU WANT?
WHAT ARE YOUR DEAL BREAKERS IN
WHAT BUILDER ARE YOU GOING TO
USE?
AND YOU START LOOKING AT YOUR
FLOOR PLAN.
YOU HAVE A PRELIMINARY PLAN THAT
GUIDES YOUR PROCESS FROM
BEGINNING TO END.
THINKING ABOUT BUILDING A
CLINICALMENT STRATEGY I S
BRAINSTORM THREE AREAS AND IT
WORKS OUT.
WHAT IS YOUR REGULATORY
STRATEGY, ASSET STRATEGY AND
OVERALL GOALS AND ASSETS PROOF
OF MECHANISM, PROOF OF PRINCIPLE
AND PROOF OF CONCEPT.
THE REASON I PRIORITIZE
REGULATORY STRATEGY IS NOT
BECAUSE IT IS MORE IMPORTANT
THAN ALL THE OTHER ELEMENTS
BECAUSE I THINK IT IS ONE OF THE
CORE ELEMENTS THAT GUIDES AND
INFORMS OVERALL PLAN.
THIS IS WHERE YOU FIGURE OUT
UNITIES FOR APPROVART
PATHWAYS.
YOU DEFINE WHAT IS YOUR IDEAL
LABEL AND WORK BACKWARDS AND
THAT WILL OFTEN DEFINE YOUR
PHASE 1 TRIAL.
WHAT ARE THE MINIMUM
REQUIREMENTS TO GET INTO THE
CLINIC?
THAT WILL DEFINITELY DEFINE THE
EXPERIMENTS YOU ARE GOING TO RUN
IN SOMEONE.
BUILDING A REGULATORY ROAD MAP
IS A GREAT TOOL THAT WE USE TO
INFORM THE CLINICAL DEVELOPMENT
STRATEGY, BUT ALSO ALLF YOUR
OTHER FUNCTIONAL STRATEGIES,
CMC, ET CETERA.
SO THEN ONCE YOU HAVE YOUR
REGULATORY STRATEGY IN PARALLEL
YOU ARE ACTUALLY WORKING ON YOUR
ASSET STRATEGY.
THE REASON I ISOLATE THE
REGULATORY STRATEGY IS BECAUSE
REGULATORY IS ONE KEY
STAKEHOLDER IN EACH OF THESE
EXERCISES.
SO AGAIN, NOT TO SAY THESE
EXERCISES ARE NOT IMPORTANT.OT
SO THEOT KEY ACTIVITY
BUILDING THE ASSET SPECIFIC
STRATEGY.
BUILDING YOUR ASSET STRATEGY
IS WHERE ONE RESEARCHS,
BRAINSTORMS AND STARTS TO PUT
PEN TO PAPER.
I DESCRIBE IT TO MANY OF MY
CLIENTS AS PUTTING ALL YOUR
STICKY NOTES ON THE WALL,
PRIORITIZING THE INDICATIONS YOU
WANT TO GO INTO OVERALL AND IN
YOUR FIRST HUMAN TRIAL.
ALL OF YOUR OPPORTUNITIES YOU
CAN DEVELOP IN YOUR PROGRAM
VERSUS LIKE YOUR FLAGSHIP
INDICATION THAT YOU ARE GOING TO
START WITH OR THAT YOU WANT TO
GO FIRST FOR APPROVAL.
BUILDING ANEGRATED
DEVELOLAN IS ANOTHER
HA CR
AND THAT FACTORS IN CROSS
FUNCTIONALLY YOUR CMC,
PRECLINICAL MARKETING
COMMERCIAL, ALL OF THESE
ELEMENTS THAT BUILD YOUR
DEVELOPMENT PLAN.
I LOOK AT IT MORE AS INTEGRATED
PLAN AND NOT JUST A CLINICAL
PLAN.
THAT HELPS FOR ALL OF THOSE
AREAS TO ALIGN CROSS
FUNCTIONALLY SO THERE IS NOT
MISCOMMUNICATION OR
MISINFORMATION.
EVEN IF IT IS JUST A SIMPLE
POWER POINT SET OF SLIDES.
DEVELOPING AN INTEGRATED TARGET
PROFILE IS ANOTHER PROCESS.
IF YOU NOTICE I'M USING THE WORD
INTEGRATED.
THAT IS WHERE YOU LOOK AT ALL OF
THOSE ELEMENTS LIKE CMC,
CLINICAL, PARAMETERS THAT FLAG
WHAT LOOKS GOOD, WHAT LOOKS BAD
AND WHAT IS GOING TO MAKE THINGS
SO AMAZING?
AND THEN AFTER THE T PP, OFTEN
WILL ENCOURAGE CLIENTS
YOUR TOP ONE TONE THREE THAT WE
CALL IT VALUE CREATION PLAN OR
MANY OTHER THINGS YOU CALL IT.
IS YOUR GO, NO GO CRITERIA.
THIS IS YOUR BIG -- COULD
TERMINATE YOUR PROGRAM OR BE
WHERE YOU DROP EVERYTHING AND GO
FAST TO APPROVAL.
SO NEXT SLIDE.
SO THEN I OFTEN HAVE CLIENTS SAY
WHY ARE WE THINKING OF PROOF OF
PRINCIPLE, PROOF OF MECHANISM
AND PROOF OF CONCEPT?
THE REASON ISNFTER YOU HAVE AN
IDEA OF REGULATORY PATH AND
OVERALL ASSET STRATEGIES THAT
TELLS YOU INDIC AND
PROPERTIES OF YOUR PRODUCT AND
HOW YOU WANT TO GET THROUGH YOUR
TRIAL AND APPROVAL.
ONE BIG EXERCISE SO TO ACHIEVE
DEMONSTRATING YOUR PROOF OF
PRINCIPAL, PROOF OF MECHANISM
AND PROOF OF CONCEPT.
THAT IT SHOULD BE DOING WHAT YOU
THINK IT SHOULD BE DOING.
IF NOT, WHAT IS HAPPENING.
IT HELPS YOU TO START TO THINK
ABOUT HOW TO MEASURE THESE
ELEMENTS BECAUSE OFTENTIMES WE
NEED LONG LEAD TIMES TO DEVELOP
CLINICAL ASSAYS.
DEFINES POM, POP AND POC WILL
DEFINE STRATEGIES AND SOME OF
YOUR END POINTS.
NEXT SLIDE.
ALL RIGHT.
CLINICAL TRIAL CONSIDERATIONS.
ONCE YOU HAVE AT LEAST A FIRST
PASS OF AN OVERALL DEVELOPMENTOA
DEEPER DIVE INTO YOUR TRIAL
DESIGN IS MUCH EASIER AND HERE
IS WHY.
I WAS TALKING ABOUT THE PROCESS
OF BUILDING A HOUSE.
BY THIS POINT YOU BOUGHT A PIECE
OF LAND, HAVE AN IDEA OF WHAT
YOU CAN AND CANNOT BUILD, THE
NUANCES OF THE LAND SURVEY AND
WRITTEN DOWN YOUR WISH LIST, THE
F MAYND HAVE
PICKED YOU FLOOR PLAN.
NOW THAT YOU HAVE ALL THOSE
THINGS IN MIND IT IS TIME TO
CUSTOMIZE YOUR BLUEPRINT.
THAT IS WHAT I CONSIDER YOUR
CLINICAL TRIAL DESIGN
CONSIDERATIONS WHERE YOU GET
INTO THE NITTY-GRITTY.
I CALL IT THE FUN PART.
NEXT SLIDE.
SO SAME THING AS A CLINICAL
TRIAL AND THAT EXAMPLE OF THE
HOUSE BUILDING.
I LOOK AT FOUR BIG BUCKETS TO
DEFINE AND GUIDE A CLINICAL
TRIAL DESIGN.
THERE ARE MANY MORE WAYS TO LOOK
AT IT.
THE VERY FIRST THING IS YOUR
PATIENT CENTERICITY.
WHAT IS HAPPENING IN REAL LIFE?
WHO ARE THE PATIENTS?
WHAT IS THEIR JOURNEY?
HOW ARE THEY TREATED?
HOW DOES YOUR ASSAY FIT THIS
PARADIGM?
WHO IS THE KEY DOCTOR OR TEAM
EA THE PATIENT?
IDEAL SITE AND
SETTING YOU NEED TO TRY TO BAKE
INTO YOUR CLINICAL TRIAL.
SO MAPPING OUT REAL LIFE
SOMETIMES WE CAN'T DO EVERYTHING
IN A CLINICAL TRIAL, BUT I
ALWAYS LAY THATWA FIRST AND I
GUIDE TO TRY TO
MODEL IT AS CLOSELY AS POSSIBLE
IN MY CLINICAL TRIAL.
AND THE NEXT IS YOUR TRIAL
DESIGN.
IT IS BUILDING YOUR PROTOCOL
SHELL.
MAPPING OUT YOUR ASSUMPASSUMPTI
POTENTIAL DESIGN,, WHAT ARE YOU
IAL OBJECTIVES AND
REMEMBER IN THE PREVIOUS
EXERCISES YOU HAVE ANSWERS LIKE
HOW WE MEASURE PROOF OF CONCEPT,
PROOF OF PRINCIPAL AND ALL OF
THAT.
ANOTHER ONE IS OPERATIONAL
PLANNING.
I MEAN, YOU NEED TO MAKE SURE
YOU KNOW WHAT IT IS GOING TO
COST, HOW LONG IT IS GOING TO
TAKE AND AGAINST HOW YOU THINK
IT IS GOING TO ENROLL.
WHAT RESOURCES YOU NEED TO GET
IT DONE.
WHO ARE YOUR VENDORS?
WHAT ARE YOUR RISKS?
BASICALLY HOW ARE YOU GOING TO
GET IT DONE?
DO YOU HAVE ALL THE RESOURCES TO
GET IT DONE? COME FROM A TRANS
MEDICINE BACKGROUND SO I AM A
LITTLE BIASED, BUT IT IS
ACTUALLY TRUE IF YOU BUILD A
CLINICAL TRANSLATIONAL PLAN
OTHER NAMES PEOPLE GIVE TO THIS,
A SIMPLE TABLE TO ITEMIZE YOUR
KEY QUESTIONS, WHAT ASSAYS CAN
ANSWER THOSE QUESTIONS, WHAT END
POINT DOES IT FEED INTO?
IS IT EXPLORATORY, IS IT
CRITICAL?
TALASIC TABLE
FRAMEW TAM CRITICAL BECAUSE IT
TIES INTO ALL OF THESE OTHER
PIECES AND YOU WILL SEE IN A
LATER SLIDE.
NEXT SLIDE.
SO THIS IS ACTUALLY, I'M NOT
GOING TO PRESENT THIS SLIDE, BUT
YOU WILL HAVE IT IN T I DECK.
THESE -- I'M PUTTING DOWN
QUESTIONS WHEN YOU ARE TRYING TO
BUILD AN EFFECTIVE BLUEPRINT
THERE ARE QUESTIONS YOU WANT TO
ASK.
TRIAL SPECIFIC QUESTIONS AND
BUSINESS QUESTIONS.
WE DO NEED TO ASK BUSINESS
QUESTIONS BECAUSE THERE ARE SOME
BUSINESS DRIVERS THAT MAY
INFLUENCE YOUR CLINICAL TRIAL
DESIGN.
FOR THE BETTER TO ENHANCE OUR
TRIAL DESIGN.
THE PURPOSE OF THIS SLIDE IS --
SORRY ABOUT THAT.
NEXT SLIDE.
ALL RIGHT.
SO WE HAVE BEEN TALKING ABOUT
THE STRATEGY AND MAPPING OUT THE
SHELL AND OUTLINING THE PEOPLE,
THE PATIENTS AND THE POTENTIAL
MARKERS.
BUT ONE THING THAT IS CRITICAL
IS REALLY UNDERSTANDING WHAT
YOU'RE TRYING TO A TH INIS
PHASE 1 TRIAL, PHASE 2, PHASE 3,
PHASE 4.
IF YOU ARE JUST STARTING OUT IT
WOULD BE A PHASE 1 OR PHASE
COMBO 2.
THIS IS GOING TO BE REALLY
IMPORTANT TO UNDERSTAND.
WHAT ARE YOUR OPTIONS FOR
INSTANCE IN YOUR PHASE 1, A
HEALTHY NORMAL VOLUNTEER,
STRAIGHT INTO DISEASE PATIENTS?
WHAT IS THAT STRATEGY?
IS IT SINGLE ASCENDING, MULTS PL
ASCENDING OR DOSE LEVELS AND
DOSE ESCALATE AND DOSE FIND TO
FIND YOUR MAXIMUM TOLERATED
DOSE?
ARE YOU LOOKING AT DRUG
INTERACTION?
PK.
SO A LOT OF THESE THINGS WILL
HELP YOU KIND OF DEFINE THE
PHASE OF TRIAL YOU NEED TO FOCUS
ON.
I'M GOING TO IN ANOTHER SLIDE
TALK MORE ABOUT INNOVATING.
BUT AT LEAST HAVE AN IDEA OF
WHAT YOUR OPTIONS ARE BECAUSE A
LOT OF TIMES PEOPLE WILL THINK
PHASE 1, I CAN ONLY DO THIS.
KNOW WHAT YOUR OPTIONS ARE
WITHIN THAT PHASE 1, 2 AREA.
A PHASE 3, WHAT ARE THE CRITICAL
ELEMENTS OF THE PHASE 3 TO GET
TO APPROVAL AND WHAT ARE
REQUIREMENTS IF YOU ARE
DESIGNING A PHASE 4?
WHAT IS THE PURPOSE?
WHY ARE YOU EVEN DOING THIS
PHASE 4 AND ACTUALLY MAKING SURE
YOU ARE FOCUSED.
SO NEXT SLIDE.
ALL RIGHT.
SO INNOVATION.
NOW MORE THAN EVER WE WANT TO
GET PRODUCTSTRORO TO PATIENTS OH
UNMET NEED AS SAFELY, BUT AS
QUICKLY AS POSSIBLE AND ALSO AS
EFFECTIVELY AS POSSIBLE.
HERE ARE SOME CONSIDERATIONS WE
SHOULD BRAINSTORM TO DETERMINE
WAYS TO INNOVATE CLINICAL
TRIALS.
IS IT POSSIBLE TO ANSWER YOUR
PROOF OF CONCEPT, PROOF OF
MECHANISM AND PROOF OF PRINCIPAL
IN AN EARLY PHASE TRIAL?
THE ANSWER IS YES.
THE WAY WE DO THAT IS WE DESIGN
A PHASE 1, 2 TRIAL.
IS IT COMPLEX?
YES.
WE ARE DOING IT A LOT NOWADAYS
SO WE ARE COMPLETE WITH THE
FIRST TRIAL WE ARE AT PHASE 2
FIGURING OUT APPROVAL PATHWAY
WITH PHASE 3.
IT IS NOT IN THIS SLIDE, BUT ONE
OF THE THINGS THAT IS REALLY
CRITICAL, IF YOUR INDICATION IS
PRIMARILY OR IT IS ADULT AND A
HUGE PROPORTION O YOUNG
PATIENTS, ONE THING I OFTEN DO
IS FIGURE OUT HOW TO BAKE IN
YOUR YOUNGER POPULATIONS SOONER
VERSUS LATER.
THAT IS ANOTHER WAY TO INNOVATE.
THAT I'VE DONE WITH A LOT OF MY
CLIENTS LIKE A PHASE 1, 2 AND IN
YOUR PHASE 2, ONCE YOU
ESTABLISHED YOUR DOSE AND WITH
ADULTS MAYBE YOU EXPLO A
COHORT WITH SOME ADOLESCENT
PATIENTS IF YOU HAVE A CERTAIN
AMOUNT OF DATA.
WE HAVE GOTTEN THAT CLEARED WITH
THE FDA VERY RECENTLY.
SO THINKING OF TRIAL DESIGN
INNOVATION WITH IN MIND OF
GETTING THAT PRODUCT AS QUICKLY
AND AS SAFELY AND AS EFFECTIVELY
ON THE MARKET FOR THE PATIENTS
THAT NEED IT.
SO NEXT SLIDE.
SO THIS IS A SLIDE THAT IS A
RESOURCEFUL TOOL.
WE TALKED ABOUT EARLIER ONE OF
THE EXERCISES OF SKETCHING OUT
YOUR SIN -- SYNOPSIS OR
CLINICAL OUTLINE.
BASICALLY WHEN PCA THINK I'M
GOING TO DESIGN AN OUTLINE
REALLY QUICK.
WE TALKED ABOUT ASSUMPTIONS, HOW
DO I GET ON PAPER TO GO PRE-IND?
THERE ARE BASIC THINGS WE WANT
TO PUT ON PAPER AND THAT IS WHAT
THIS LIST IS HERE I A BASIC LIS
OF YOU WOULD WANT TO PUT
ON PAPER TO HAVE THAT FIRST
OUTLINE.
ON PAPER.
SO THE POINT P THIS SLIDE IS
THAT EARLIER THERE'S ALL THIS
BRAINSTORMING HAPPENING AND ALL
THESE DISCUSSIONS AND
ASSUMPTIONS AND YOU HAVE FIGURED
OUT THE TREATMENT JOURNEY OF THE
PATIENTS AND ALL OF THAT, THE
HARDEST PART TO ME SOMETIMES IS
NOW HOW DO WE ACTUALLY PUT THIS
ON PAPER IN A WAY THAT IT'S GOT
SCIENTIFIC AND CLINICAL MERIT?
THIS IS A REALLY GOOD OUTLINE
THAT HELPS PRIORITIZE THE TOPICS
YOU NEED TO FOCUS ON FIRST WHEN
YOU ARE TRYING TO DESIGN YOUR
CLINICAL TRIAL AND PUT IT ON
PAPER.
NEXT SLIDE.
SO CLINICAL TRIAL EXECUTION.
SO YOU CAN GO TO THE NEXT SLIDE.
IT IS JUST ONE SLIDE.
HOWEVER, WHILE THIS IS ONLY ONE
SLIDE, THERE ARE SO MANY MOVING
PIECES IN TRIAL PLANNING AND
EXECUTION.
MANY TIMES PEOPLE DON'T REALIZE
ALL OF THAT EARLY STRATEGY I WAS
TALKING ABOUT AND PLANNING
SOMETIMES, YOU KNOW, PEOPLE
OVERLOOK THE FACT THAT THIS
HEAVILY INFLUENCED THE CLINICAL
TRIAL DESIGN AND EXECUTION
STRATEGY.
SO IT ALWAYS IS IMPORTANT TO
HAVE A CLINICAL OPERATIONS
PERSON OR MEMBER AS PART OF
THOSE EARLIER EXERCISES BECAUSE
THEN THAT PERSON HAS TO FIGURE
OU TO SET UP THE TRIAL AND
IMPLEMENT IT.
AND SO WHEN USING THAT HOUSE
BUILDING SCENARIO, THIS IS WHERE
YOU PICK YOUR CABINETS, YOUR
FLOORS, THE FINE DETAILS LIKE
THE DOORKNOBS, WHAT COLOR DOORS
YOU WANT, WHAT STYLE CABINETS
AND COUNTER TOPS.
SOME OF THESE THINGS YOU CAN
CHANGE LATER, BUT IT WOULD I OUY
IMPORTANT YOU HAVE A GOOD IDEA
OF THAT PLANNING, THAT BLUEPRINT
AND YOU CAN DO THE FINISHING
TOUCHES.
THAT IS HOW I LOOK AT THIS
SCENARIO.
SO FOR EXAMPLE WHEN MAPPING OUT
THE REAL LIFE JOURNEY WE LEARN
WHAT TYPE OF PI YOU NEED TO GO
TO, WHAT SPECIALTY.
WHAT SITE SETTING YOU NEED TO
LOOK FOR SO YOU CAN KNOW WHAT
SITES TO IDENTIFY?
WHAT OPERATIONAL ELEMENTS ARE
NEEDED IN PLACE?
THE CRITICAL TRANSLATION PLAN
TELLS YOU WHAT
VENDORS YOU
NEED TO PICK.
SO THIS IS WHY IT IS IMPS
FO INDIVIDUALS THAT ARE
INVOLVED IN THE CLINICAL TRIAL
EXECUTION STRATEGY THAT THEY ARE
ALSO PARTICIPATING IN THE EARLY
DISCUSSIONS.
FOR CLINICAL TRIAL EXECUTION
STRATEGY THERE ARE ELEMENTS
PEOPLE DON'T THINK ABOUT THAT
MAY HEAVILY ENFORCE EXECUTION.
A COMPANY'S COMMERCIAL STRATEGY.
I ALWAYS TRYO , YOU
KNOW, WE'RE NOT ALWAYS WANTING A
BUSINESS TO TELL US HOW TO RUN
OUR TRIALS, HOWEVER THERE MAY BE
A COMMERCIAL STRATEGY THAT
GUIDES US INTO WHAT COUNTRIES WE
SHOULD GO INTO.
THEN AT THE SAME TIME AS A
CLINICAL OPERATION PERSON YOU
MAY BE THINKING WHERE ARE YOUR
PATIENTS HEAT MAP WISE?
THERE IS A DIFFICULT BALANCE
SOMETIMES TO FIGURE OUT HOW TO
BAKE IN ALL OF THE ELEMENTS
WHETHER IT IS COMMERCIAL, MAYBE
CMC THAT CAN'T GET KITS BY A
CERTAIN TIME OR I.V.BOLUS BUT
YOU PREFER A LONGER I.V.
THESE THINGS FEED INTO CLINICAL
TRIAL EXECUTION.
WHEN YOU ARE MAPPING OUT YOUR
TIMELINES THERE MAYBIN FLEXION
POINTS THAT ARE CRITICAL PATHS
FOR THE COMPANY OR CRITICAL PATH
TO BE ABLE TO INFORM WHETHER WE
DO A BID DOSE OR A COMBINATION
OR WHETHER IT IS SAFE FOR THE
PATIENT.
AYS COMES P FIRST,
WE NEED TO FACTOR IN THESE
ELEMENTS AND THE CLINICAL TRIAL
EXECUTION AND HOW WE ARE GOING
TO SET IT I.
THE LAST POINTS I'M GOING TO
MAKE IS WE HAVE GONE BACK AND
FORTH OF HOW WE SEE RECRUITMENT
STRATEGIES AND TACTICS.
I LIKED THE WAY THE PREVIOUS
SPEAKER TALKED ABOUT RECRUITMENT
STRATEGIES AND TACTICS.
I ALWAYS ENCOURAGE MY CLIENTS TO
GO BACK TO THE PATIENT AND THE
TREATMENT JOURNEY MAPPING AND
PUT THE PATIENT IN THE CENTER
AND FIGURE OUT THE BEST
RESOURCES AND ENGAGEMENTS THAT
WILL BUILD HEALTHY
SELF-AWARENESS ABOUT THE TRIAL.
ENGAGING PATIENT FOUNDATION AND
ADVOCACY GROUPS EARLY TO HELP A
DEVELOPER TO GET MORE CONNECTED
TO THE COMMUNITY, BUT MORE
IMPORTANTLY UNDERSTANDING THE
PATIENT BETTER AND SETTING UP AN
OPTIMAL PATIENT RECRUITMENT
RETENTION TOOLS THAT HELP THE
PATIENT NAVIGATE THROUGH THE
NUANCES AND CHALLENGES OF
PARTICIPATING IN A TRIAL.
I THINK WE DO ALL THESE THINGS,
WE WANT GOOD DATA, WE WANT THE
TRIAL TO BE, YOU KNOW, EASY FOR
THE SITE TO BE ABLE TO
IMPLEMENT, NOT MAKE A LOT OF
MISTAKES, ALL THESE THINGS.
AT THE END OF THE DAY, I TRY TO
ALWAYS PUT THE PATIENT FIRST AND
SAY, YOU KNOW, HOW DOES THIS,
YOU KNOW, HOW WOULD THE PATIENT
NAVIGATE THIS TRIAL?
WHAT IS GOING TO MAKE IT
IMPOSSIBLE?
YOU KNOW, WHEN WE ARE THINKING
ABOUT FRESH BIOPSIESIEIEERSUS
GETTING AN HISTORICAL REPORT.
THESE KINDS OF THINGS REALLY
MATTER AND BALANCING OUT YOUR
SCIENTIFIC MERIT AND THE
CLINICAL QUESTIONS YOU NEED TO
ANSWER IN YOUR TRIAL.
AND SOHESE THINGS ARE
EXTREMELY IMPORTANT WHEN YOU ARE
THINKING ABOUT OPERATIONAL
PLANNING AND EXECUTION.
SO THAT'S THE END OF MYPRESENTA.
>> THANKS SO MUCH, DORIS.
WHAT A GREAT SUMMARY OF A VERY,
VERY COMPLICATED PROCESS.
NICE WORK TO DO THAT IN 20
MINUTES.
WE'LL MOVE ON TO D DETERDING
TO TELL US HOW THIS PROCESS WENT
FOR HER IN HER TRIAL.
>> HI, EVERYBODY.
I'M EXCITED TO TALK WITH YOU W
THROUGH THINKING ABOUT CHILDREN
WITH RARE LUNG DISEASE.
AND AS PART OF THIS, I WILL
MENTION WAYS THAT WE'VE HAD TO
ADAPT, BARRIERS AND SOLUTIONS
THAT WE ARRIVED AT THAT OTHER
PEOPLE CAN THINK ABOUT.
NEXT.
I DO HAVE SOME CONFLICT OF
INTEREST RELEVANT FINANCIAL
RELATIONSHIPS AROUND BEOHRINGER
INND THE FRE
FOUNDATION AND THE REST YOU CAN
SEE.
NEXT.
SO I JUST WANTED TO START BY
PROVIDING THE CLINICIAN'S
PERSPECTIVE OF TREATMENT,
ESPECIALLY IN KIDS WITH RARE
LUNG DISEASE.
AND THIS IS WHAT WE DO.
SOME OF THE CLINICIANS ON WILL
UNDERSTAND THIS.
WE USE OFF LABEL DRUGS.
THIS IS OUR STANDARD WAY WE
APPROACH THINGS.
MOST DRUGS AREN'T STUDIED IN
CHILDREN.
THE BENEFIT IS THEYRE
AVAILABLE, WE HAVE INSIGHTS FROM
MMON THING.MENTUL MOST
THERE ARE A LOT OF RISKS.
WE DON'T KNOW INFORMATION ABOUT
DOSING, PROFILE ON KIDS,
SOMETIMES THEY ARE NOT COVERED
BY INSURANCE AND SOMETIMES
UNPROVEN.
WE GET TO CLINICAL TRIALS WITH
DRUGS AVAILABLE IN THE ADULT
MARKET THIS HAPPENS, THERE IS
NOW A MOVEMENT BY FDA AND EMA T
CONSIDERATION OF DRUGS AND WE'LL
TALK ABOUT SOME OF THAT.
THAT LED US TO THE TENTATIVE
TRIAL FOR KIDS WITH PULMONARY
FIBROSIS.
THESE DRUGS ARE USUALLY TESTED
IN ADULTS FIRST.
THERE IS ADULT DATA AND THE
REGULATORY REQUIREMENTS INCLUDE
THERE SHOULD BE A PEDIATRIC
INVESTIGATION PLAN.
THIS IS OPENED UP OPPORTUNITIES
FOR KIDS TO HAVE DRUGS STUDIED
AND BRING DRUGS FORWARD,
HOWEVER, IT IS A VERY EXPENSIVE
ENDEAVOR.
WE HAVE FEW PATIENTS THAT HAVE
TO GO THROUGH REGULATORY
APPROVAL AND IT TAKES TIME.
BUT I'M GOING TO BE TALKING
ABOUT THAT TODAY.
THEN THERE'S NEW DISCOVERY.
THERE HAS BEEN SOME EXCITING
SCIENCE.
MORE MECHANICISTICS, GET TO
CURING DISEASE.
IT IS SO EXCITING, IT CAN BE
RISKY, EXPENSIVE.
I HOPE WE HAVE NEW MODELS, BUT
IT CAN TAKE A LONG TIME.
THIS IS CURRENTLY AS A CLINICIAN
WHAT WE LOOK AT AND AS AN
ADVOCATE FORCAG CAREF KIDS
THAT WE DO.ISEASE THAT I SEE I
NEXT.
THAT SETS THE STAGE FOR HOW WE
ARRIVE AT THE FIRST CLINICAL
TRIAL FOR KIDS WITH REALLY
PULMONARY FIBROSIS.
THAT IS WHAT I WILL BE TALKING
ABOUT TODAY.
WE WERE APPROACHED ABOUT
CONDUCTING A TRIAL FOR CHILDREN
FOR THEIR PEDIATRIC
INVESTIGATIONAL PLAN FOR
ATTENTIVE.
OUR SCIENTIFIC COMMUNITY WAS
APPROACHED ABOUT RUNNING A
TRIAL.
IT WAS QUITE EYE OPENING BECAUSE
WE DON'T REALLY HAVE RESOURCES.
I WAS THINKING ABOUT THE LAST
SPEAKER, THINKING ABOUT YOUR
RESOURCES.
WE DON'T HAVE RESOURCES, REALLY,
LIMITED RESOURCES.
SO THIS WAS A GREAT OPPORTUNITY
TO THINK ABOUT MOVING THE FIELD
FORWARD FOR KIDS.
THERE WAS A LOT WE DIDN'T KNOW
WHEN WE SAT DOWN.
TALKING ABOUT BARRIERS AND
TALKING ABOUT WHAT CAN HAPPEN
THOUGH.
WE HAD A WHOLE LIST OF THINGS WE
HAD TO THINK ABOUT TO DEFINE
THIS STUDY.
WE HAD TO DEFINE WHAT FIBROSIS
WAS IN CHILDREN.
WHAT EXACERBATIONS WERE, WHAT
PEDIATRIC CHILD PROGRESSIVE
FIBROSIS DISEASES WOULD BE
NATURAL HISTORY.
WE DON'T HAVE -- WE ARE EVOLVING
REGISTRIES, BUT NATURAL HISTORY
IS SO IMPORTANT.
AND THAT WAS SOMEWHAT MISSING.
YOU CAN SEE THE WHOLE LIST.
BASICALLY HAD TO START FROM
SCRATCH TO GET DOWN TO DIVINE
THIS STUDY AND THIS TRIAL.
SO THIS WAS A LEAP OF FAITH FROM
TO DESIGN A
TRIAL TO GET T WHERE WE ENDED
UP, WHICH I'M VERY PROUD OF.
ONE OF THE THINGS I WILL TALK
ABOUT TODAY, NEXT, WE NEED TO
THINK ABOUT DIFFERENCES BETWEEN
ADULT AND CHILD PULMONARY
FIBROSIS.
NEXT.
THE PREVIOUS SLIDE GAVE A LOT OF
BARRIERS IF YOU DON'T KNOW THOSE
THINGS.
WE HAD TO WORK THROUGH ALL
THOSE.
THE FIRST THING IS THERE A NEED?
ARE THERE CONDITIONS WITH
FIBROSIS IN PEDIATRIC
INTERSTITIAL LUNG DISEASE?
THE ANSWER IS THERE ARE.
YOU HEART ABOUT SURFACTANT
PROTEN DEFICIENCY AND THERE I A
LIST OF KIDS WITH FIBROSIS THAT
INCLUDE HIGH MORBIDITY, HIGH
MORTALITY CONDITIONS.
PULMONARY FIBROSIS IS ALL OF
THAT AND WE HAVE VERY FEW
TREATMENT OPTIONS.
NEXT.
SO SPEAKING OF WHAT WE DO AS
CLINICIANS, AS I TOLD YOU, WELL,
WE USE OFF-LABEL TREATMENT AND
ANECDOTAL TREATMENT APPROACHES.
THIS IS THE CURRENT APPROACH.
THAT WE APPROACH KIDS WITH
INTERSTITIAL LUNG DISEASE OR
PULMONARY FIBROFIBROSIS.
THE WHOLE COMMUNITY DOES THE
SAME THING BUT NONE OF THIS ISF
STUDIED.
WE THEN THINK ABOUT MED
DISEASES AND WE HAVE OTHER SET
OF MEDICATIONS THAT HAVE BEEN
EVOLVING IN THE RHEUMATOLOGIC
SPACE.
NONE OF THESE HAVE BEEN
EXCLUSIVELY STUDIED IN S CHILDR.
THIS CAU
GREAT PAUSE.
WE LEARN A LOT FROM OUR ADULT
COLLEAGUES.
OUR ADULT COLLEAGUES HAVE MORE
PATIENTS.
WE PAY ATTENTION IN WHAT HAPPENS
TO THEM TO BRING THE BEST TO
CHILDREN.
THIS STUDY HIGHLIGHTS WHY WE
NEED PLANS FOR KIDS TO HAVE DRIG
STUDIES.
THIS STUDY, THE PANTHER TRIAL
WAS CONDUCTED IN ADULTS WITH
PULMONARY IS.
WHAT THEY LOOKED AT IS NOW THIS
IS IN 2012, SO IT WAS A WHILE
AGO.
THEY LOOKED AT THEIR STANDARD OF
CARE AT THE TIME WAS PREDNISONE
AND -- THE RESULTS WERE VERY EYE
OPENING.
IN ALMOST EVERY OUTCOME END
POINT FROM DEATH TO
HOSPITALIZATION TO
EXACERBAHE TREATMENT ARM
WAS THE HIGHEST RISK FOR DEATH,
FOR ALL OF THAT.
AND I THINK THAT HIGHLIGHTS THAT
WE HAVE TO DO MORE, WE HAVE TO
DO THESE STUDIES FOR KIDS.
WE HAVE TO ADVOCATE THAT THESE
THINGS HAPPEN.
WE USE SOME OF THESE MEDICATIONS
IN KIDS.
NEXT.
SO IT CAUSES US TO LOOK TO WHAT
IS HAPPENING IN THE ADULT REALM.
KIDS WITH PULMONARY FIBROSIS,
MEDICATIONS HAVE BEEN APPROVED
SINCE 2014.
BIG PHASE 3 TRIALS HAVE BEEN
DONE.
SO THE QUESTION WE ASK IS HOW DO
WE GET ACCESS TO THESE TRIALS?
HOW DO WE GET ACCESS TO THESE
DRUGS FROM A TRIAL?
OUR COMMUNITY HAS BEEN ASKING
THESE QUESTIONS.
NEXT.
SO THE TRIALS HAVE INCLUDEDLU
DIOPATHIC PULMONARY FIBROSIS
STUDIES.
SYSTEMIC SCLEROSIS SOERTED ILD
AND PROGRESSIVE FIBROSING ILD.
THE COMMUNITY SAID, HEY, THESE
DISEASE STUDIES FOR PULMONARY
FIBROSIS, WE ARE NEVER GOING TO
GET TO PATIENTS WHO NEED HELP.
WE H PATIENTS THAT THESE
MECHC DRUGSTIFERE IN
THE FIBROTIC PATHWAY.
THEY DEVELOPED A STUDY WHERE
THEY TOOK ADULT CONDITIONS WITH
PROGRESSIVE FIBROTIC LUNG
DISEASE AND BASKETED THOSE
DISEASES INTO A COHORT TO STUDY.
THAT BECAME VERY IMPORTANT.
ALL OF THESEPREWORK WAS
CRITICALLY IMPORTA GETTING
TO A PEDIATRIC STUDY.
CO APPROACHED US, WE
APPROACHED THEM AND WERE ABLE TO
CONCEIVE OF THIS STUDY AND I'LL
EXPLAIN WHY.
NEXT.
SO THE GOOD NEWS IS IN ALL THE
STUDIES WHERE THIS DRUG WAS USED
IN DIFFERENT CONDITIONS, WHETHER
IT BE IPF, SYSTEMIC SCLEROSIS OR
THE INBUILD STUDY YOU SEE HERE,
THE DRUG SLOWED THE CHANGE FROM
BASELINE.
THE PRIMARY END POINT FOR MOST
REGULATORY APPROVAL PATHWAYS FOR
DRUGS.
IN THIS STUDY THE NINTENATIVE
GROUP, IPF OR ALL COMMERCE
SLOWED LUNG DECLINE WITH
FIBROSING ILDs.
THAT OCCURRED IN ALMOST ALL OF
THE PHASE 3 STUDIES.
NEXT.
SO WE SAID THIS INDICATIONS FOR
US TO STUDY THIS IN CHILDREN IS
WE BELIEVE THAT THE
PATHOPHYSIOLOGY O FIBROSIS IN
ADULTS AND CHILDREN ARE SIMILAR
ENOUGH WE SHOULD PROCEED.
YES, THERE IS A DEVELOPMENTAL
BACKGROUND FOR CHILDREN.
THE FIBROTIC MECHANISMS AND
PATHWAYS WOULD BE SIMILAR ENOUGH
FOR THIS MEDICATION TO BE
EFFECTIVE.
MODES OF ACTION THAT INHIBIT
PROGRESSIVE FIBROSIS WOULD BE
THE SAME.
ESTABLISHING CLINICAL BENEFIT OF
NINTEDANIB IN ADULTS COULD
HAPPEN SO WE COULD TAKE OUR
SMALL POPULATIONS AND COMBINE
THEN INTO ONE FIBROSING
PEDIATRIC POPULATION.
THESE WERE OUR CONSIDERATIONS.
NEXT.
AND SO THAT'S WHAT WE DID.
WE CAN DO THAT, TOO.
WE CAN USE THE BASKET APPROACH
IN KIDS.
I JUST SHOWED YOU THE LIST OF
PATIENTS THAT HAD PULMONARY
FIBROSIS.
WE CAN CREATE THAT SAME BASKET
APPROACH TO C T OURPOPULATION T.
NEXT.
UH-OH.
NE
COULD WE ADVANCE THE SLIDES,
PLEASE.
>> ANTONE, ARE YOU WITH US?
>> YES, ONE SECOND, MY COMPUTER
FROZE.
>> I'LL FILL THE GAP.
OKAY.
THANK YOU.
SO THIS LED TO A TRIAL THAT HAS
BEEN SUCCESSFULLY COMPLETED
WHERE WE LOOKED AT NINTEDANIB IN
CHILDREN AND ADULTS WITH
FIBROSING INTERSTITIAL LUNG
DISEASES.
I DON'T HAVE TIME TO PRESENT ALL
THE STUDY.
I'M GOING TO PRESENT HIGHLIGHTS
THAT ARE IMPORTANT TO THINK
ABOUT AS WE MOVE FORWARD WITH
KIDS WITH DIFFERENT TYPES OF
PROBLEMS AND PERHAPS THIS STUDY
CAN BE HELPFUL IN THINKING ABOUT
DESIGNINS FIN
SO OUR KEY INCLUSION CRITERIA
FOR THE INPED ILD TRIAL, 6-17
YEARS OF AGE.
EVIDENCING OF FIBROSING ILD ON
HRCT, FVC GREATER THAN 25%.
CLINICAL SCORING OF DISEASE.
PEDIATRICS WERE DIFFERENT FROM
ADULTS.
WE HAD TO DESIGN HOW KIDS COULD
MTS.DIFFERENT FROM
WE USED A PLAN SCORING SYSTEM
WHICH LOOKS AT HOW OXYGEN IS
USED IN CHILDREN.
THAT WAS PART OF OUR DESIGN.
THAT WAS A NEW DESIGN AND THE
CLASSIC MEASUREMENTS BY CAPACITY
THAT ARE STANDARD IN CLINICAL
MEASURES OF CLASSIC FIBROSIS.
SO THESE KIDS TO BE SI
NEXT.
ONE OF THE KEY BARRIERS WE GOT
TO ALMOST RIGHT AWAY IS THAT FOR
MANY OF THESE KIDS WITH
FIBROSIS, THE EASIEST WAY TO
DIAGNOSE FIBROSIS IS A LUNG
BIOPSY.
BUT AS MORE AND MORE OF THESE
FIBROTTIC CONDITIONS WERE
DIAGNOSED, THESE KIDS WERE NOT
GETTING LUNGES.
WEAD TO THINK OF OTHER
CRITERIA THAN THE GOLD STANDARD
OF LUNG BIOPSY.
THERE WAS NO C T CRITERIA FOR
LUNG FIBROSIS AT THE TIME WE
INITIATED THIS STUDY.
OUR IMAGEERS GOT AFTER IT WITH
ADULT COLLEAGUES TO CREATE AN
IMAGING DIAGNOSIS OF FIBROSIS
WORKING WITH ADULT IMAGEERS,
LOOKING AT ADULT STUDIES AND
MAKING A DIAGNOSIS OF PEDIATRIC
LUNG FIBROSIS NOT IN THE
LITERATURE.
SO THIS IS ONE OF THE FIRST
BARR HAD TO ANDMEALLY WE DEVEL
CHANGED THE FIELD BECAUSE NOW
PEDIATRIC PULMONOLOGISTS ARE
LOOKING TO RADIOLOGISTS TO MAKE
THIS CALL ON KIDS WITH PULMONARY
FIBROSIS.
THIS WAS A BIG BARRIER WE
OVERCAME IN OUR DESIGN.
NEXT.
AGAIN, LUNG BIOPSIES ARE THE
GOLD STANDARD FOR FIBROSIS.
YOU CAN SEE CLASSIC LUNG
FIBROSIS STUDIES HERE, BUT AS I
SAID AND AS YOU HAVE HEARD, AS
MORE AND MORE JEANEGENETIC DISE
DOESN'T ALLOW US TO USE GOLD
STANDARD DIAGNOSIS FOR FIBROSIS.
SO CT SCAN OR INCLUSION BECAME
CRITICALLY IMPORTANT.
WE ARE BEGINNING TO GRAPPLE WITH
HOW DOES THIS LOOK DIFFEN
ADULTS AND PEDIATRICS AND
LOOKING FOR KIDS TO BRING TRIALS
FORWARD WITH, THERE IS A
DEVELOPMENTAL PROCESS, THERE IS
GROWTH IN THE LUNG, THERE ARE
CHANGES OVER TIME SO THOSE HAVE
TO BE INCLUDED.
AS WE THINK ABOUT IT, THERE HAS
TO BE MORE PATHOPHYSIOLOGIC
COMPARISONS TO IMAGING.
THAT WORK STILL NEEDS TO BE
DONE, BUT WE WERE STILL ABLE TO
MOVE FORWARD WITH THIS STUDY IN.
NEXT.
SO THIS STUDY WAS CONDUCTED,
THIS WAS A WORLDWIDE GLOBAL
STUDY.
VERY PROUD OF OUR COMMUNITY.
IT WAS CONDUCTED IN 53 LOCATIONS
IN 22 COUNTRIES.
THIS WAS A REAL TRIBUTE TO OUR
COMMUNITY AROUND THE WORLD
BANDING TOGETHER TO THINK ABOUT
KIDS WITH RARE DISEASE, IN A
COMMUNITY THAT NEVER CONDUCTED A
TRIAL.
I'M VERY PROUD OF THIS TRIAL IN
THAT TRIAL WAS CONDUCTED DURING
COVID.
IT HAD TO START AND RESTART.
THERE WERE SOME BARRIERS GETTING
THIS TRIAL OFF THE GROUND.
NEXT.
THE DESIGN OF THIS STUDY WAS
REALLY A TWO TO ONE NINTEDANIB
PLA SEENO, DOUBLE BLIND PLACEBO
CONTROL.
THE REST OF THE TRIAL IS 52
WEEKS SO THIS DESIGN WAS FAIRLY
CLASSIC.
MOST OF THE DATA WE EVALUATED
AROUND EFFICACY AND SITE EFFECT
PROFILE CAME FROM THE 20 WEEKS
OF THE DOUBLE BLIND PERIOD.
NEXT.
SO OUR OUTCOME MEASURES WERE
PRTLY PRIMARILY PK AND
SAFETY.
WE DID LOOK AT OTHER STUDY
MEASURES THAT WERE EXPLORED.
EFFICACY RELATED TO PULMONARY
FUNCTION.
THIS STUDY WAS NOT POWERED FOR
ANY OF THESE OTHER IMPACTS.
EXPLORE
CT SCANS,
EXPLORATORY BIOMARKERS.
WE HAVE PUBLISHED OND THIS
RELATED TO HRCT IS COMING
WE HAVE A BIOMARKER STUDY COMING
AND WE'VE HAD THIS IN ABSTRACT
FORM.
NEXT.
SO THIS WAS THE WAY THE DOUBLE
BLIND PLACEBO GROUPS WERE
ENROLL.
WE HAD 8' PATIENTS SCREENED.
WE HAD A CLINICAL OVERSITE
COMMITTEE THAT REVIEWED CRITERIA
FOR ENROLLMENT.
OUR COMMUNITY HAD NOT DONE THESE
STUDIES BEFORE.
WE WERE DEALING WITH NEW
DEFINITIONS FOR FIBROSIS AND THE
MAJORITY OF THESE PATIENTS THAT
WERE NOT INCLUDED, WERE NOT
INCLUDED BECAUSE PATIENTS WERE
TRYING TO ENROLL PATIENTS WITH
BRONCULITIS.
35 WERE RANDOMIZED TOOPLACEBO.
THE MAJORITY OF PATIENTS DID
COMPLETE THIS TRIAL.
NEXT.
THE DIAGNOSES ENROLLED, THE
SURFACTANT PROTEIN DEFICIENCY,
THE MOST COMMON DEFINITION IN
PATIENTS THAT WERE ENROLLED,RO
SYSTEMICSY SCLEROSIS PATIENTS WE
ENBUT OF NOTE, THE
LARGEST GROUP OF PATIENTS WITH
DIAGNOSE OF ONE WITH FIBROSIS.
MANY PATIENTS HAVE PULMONARY
FIBROSIS.
SO THIS IS A BASKET APPROACH TO
KIDS WITH PULMONARY FIBROSIS.
NEXT.
SO AT THE END OF THE DAY I'M NOT
GOING TO TAKE YOU THROUGH ALL
THE STUDY, BUT I WILL TAKE YOU
TO THE STUDY.
NINTEDANIB HAD AN ACCEPTABLE
SAFETY AND TOLL REHABILITATE
PROFILE WITH NO NEW SAFETY
SIGNALS COMPARED TO ADULTS.
THAT WAS A HUGE SUCCESS.
WE WERE ABLE TO DO WEIGHT-BASED
DOSING.
AS A PEDIATRICIAN WE HAVE TO DO
WEIGHT-BASED DOSING TO GET IN
THE SAME TREATMENT RANGES ANDM .
WE WERE ABLE TO DO WEIGHT-BASED
DOSING AND GET IN THE RIGHT
RANGES FOR ADULTS.
WE LOOKED AT EFFICACY MEASURES
TO TREND.
TRENDED IN FAVOR OF
NI THOSE THIS WAS NOT
POWERED FOR THAT.
WE DO HAVE AN INPEDILD ON STUDY
THAT ENROLLED NEW PATIENTS TO
LOOK AT ONGOING SAFETY.
OUR SCIENTIFIC COMMUNITY
BELIEVES THAT THIS DATA SUPPORTS
POSITIVE BENEFIT RISK ASSESSMENT
FOR THE USE OF NINTEDANIB FOR
USE IN CHILDREN WITH DOSING
INPED ILB.
NEXT.
I WILL FLENGS HAVE -- MENTION
THERE HAVE BEEN OTHER PAPERS
PUBLISHED.
THESE AYSEIAN DYNAMIC APPROACHES
TO TAKE A SMALL POPULATION, OUR
GROUP, ADD IN DATA FROM THE
ADULT STUDIES, LOOKING AT THOSE
ADULT STUDIES, META ANALYSIS OF
THOSE ADULT TRIALS AND THEN ADD
THEM TO OUR STUDY, OUR DATA FROM
THE PEDIATRIC TRIAL AND COME UP
WITH SOME IDEA OF EFFICACY.
SO WE WERE ASKED TO DO THESE
BAY
BAYESIAN TRIALS.
WE HAD TO DO PRESPECIFIED
WEIGHTING OF HOW MUCH PEDIATRIC
ILD WAS LIKE ADULT ILD TO DO
THESE STUDIES.
AT THE END OF THE DAY WE WERE
ABLE TO LOOK AT OUR FINDINGS FOR
PULMONARY FUNCTION AND COMBINE
DECIDE WHETHER THE EFFICACY NOW
WITH THE POPULATION THAT WAS
POWERED TO LOOK AT THIS WAS
STILL SUBSTANTIAL.
NEXT.
SO THIS IS FROM THE PAPER WE
EFESSEF OF NINTEDANILB
OVER THE DOUBLE BLIND PLACEBO
CONTROL.
THERE IS A 1.65 DIFFERENCE IN
THE NINTEDANIB GRUBE FROM
PLACEBO GROUP.
OUR TRIAL WAS 1.2 PERCENT
DIFFERENCE BETWEEN NINTEDANIB
AND THE PLACEBO.
WHEN YOU LOOK AT THE COMBINED
BAYESIAN ANALYSIS THERE IS 137B9
63.
THAT HAS BEEN POWERED TO LOOK AT
EFFICACY.
REQUIRED BY THE REGULATORY
AGENCIES TO EXPLORE THAT.
THESE BAYESIAN TECH TEAKS ARE
IMPORTANT WITH SMALL POPULATIONS
AND OUR DATA USING THESE
TECHNIQUES WAS SIGNIFICANT.
NEXT.
SO I WANT TO HIGHLIGHT THIS AS I
HAVE HAD TO SAY THIS MANY TIMES
BECAUSEES THINK IT IS SO T
IMPORTANT.
THE TENTATIVE IS THE MOST
STUDY -- NINTEDANIB IS THE MOST
STUDIED DRUG I CAN PRESCRIBE FOR
A CHILD WITH FIBROSIS.IS KNOWHE
THE DOSING.
I KNOW BASED ON STATISTICAL
ANALYSIS THERE APPEARS TO BE
EFFICACY AND IT IS THE MOST I
KNOW.
THE STUDY I SHOWED YOU ABOUT
WHON'T KNOW AND POTENTIAL
RISKS TO PATIENTS CAUSES ME
GREAT PAUSE.
THIS IS AN IMPORTANT STATE.
WHAT REGULATORY ACTION HAS
HAPPENED?
A BIG BREAK THROUGH OF PEDIATRIC
INVESTIGATIONAL PLANS ARE BEING
REQUIRED BY FDA AND EMA.
IT ALLOWED KIDS TO BE OPEN TO P.
NEXT.
SO THE FDA.
RESPONSE LETTER IN REGARD TO OUR
TREATMENT.
NEXT.
NEY FOUND THAT FDA COULD NOT
APPROVE THE APPLICATION IN ITS
CURRENT FORM FOR CHILDREN.
NEXT.
BUT THEY SAID THIS LETTER HAD NO
IMPACT ON OUR ABILITY TO
CONTINUE WITH THE INPED STUDY TO
LOOK AT NINTEDANIB IN CHILDREN
IN AN OPEN LABEL FASHION.
SO DID NOT GRANT
PEDIATRIC INDICATION FOR THE
MOST STUDIED DRUG OF KIDS COULD
I HAVE FOR PULMONARY FIBROSIS.
THERE IS BREAKING NEWS AS OF
LAST WEEK.
NEXT.
EMA, THE EUROPEAN MEDICAL
AGENCY, IF YOU ARE NOT FAMILIAR
WITH THIS IS SIMILAR TO THE FDA
IN EUROPE.
HAS NOW RECOMMENDED THE APPROVAL
OF NEW INDICATIONS AND THE
INDICATIONS OF EXTENSION OF
NINTEDANIB TO CHILDREN.
NEXT.
THEY RECOMME T APPROVAL FOR
OFEB FHILDREN FOR THE
TREATMENT OF CLINICALLY
SIGNIFICANT PROGRESSIVE
INTERSTITIAL LUNG DISEASE.
AND IN KIDS WITH SYSTEMIC
SCLEROSIS.
SO THEY GAVE TWO NEW LABELS
PROGRESSIVE FIBROSIS IN CHILDREN
6-17 YEARS OF AGE AND CHILDREN
6-17 WITH SYSTEMIC SCLEROSIS.
NEXT. WE ARE VERY PROUD OF THIS.
THIS WILL BECOME THE FIRST
APPROVED TREATMENT FOR CHILDREN
WITH FIBROSIS ABOVE THE AGE OF 6
AND FOR SYSTEMIC SCLEROSIS.
WE BELIEVE THIS HELPS VALIDATE
OUR CLINICAL DESIGN, OUR
ASSUMPTIONS AND THE WORK WE HAVE
DONE TO OVERCOME MANY RS,
BUT WE HAVE WORK TO DO
WITH FDA AND REGULATORY IN THE
U.S. ABOUT HOW TO GET DRUGS
FORWARD.
AND HOW TO THINK ABOUT THIS IN
NEW WAYS.
SO THIS IS A BARRIER WE ARE
GOING TO BE APPROACHING.
NEXT.
SO THE NINTEDANIB CLINICAL TRIAL
HAS HAD TREMENDOUS IMPACT ON
PEDIATRIC PULMONARY FIBROSIS.
I CAN'T TELL YOU HOW IT
JETSONNED THE FIELD FORWARD.
WE DON'T HAVE RESOURCES.
IT SHOWED OUR COMMUNITY CAN DO
THIS.
WE CAN DO IT WORLDWIDE.
I'M VERY PROUD OF OUR COMMUNITY.
I CONSIDER REALLY A GRAND SLAM.
WE HAD MAJOR ADVANCES ACHIEVED
DURING THIS STUDY.
NEW DEFINITIONS OF PULMONARY
FIBROSIS IN IMAGING WERE ARRIVED
AT.
PRIOR TO THIS STUDY PEDIATRIC
RADIOLOGISTS WERE TOLD TO NOT
COMMENT ON FIBROSIS.
NOW THIS DEFINITION IS
FORTHCOMING PEDIATRIC
RADIOLOGISTS ARE BEING TOLD
ABOUT THE DIAGNOSIS AND THE
INDICATIONS AND CRITERIA FOR
FIBROSIS AND THOSE CTs ARE READ
AS FIBROSIS THAT GETS YOU TO THE
PULMONOLOGIST FAST.
IT IS MORE COMMON THAN YOU THINK
SO THIS IS A MAJOR ACHIEVEMENT
TO HAVE A DIAGNOSIS WITH CT THAT
CAN BE EDUCATED THROUGH THE
PEDIATRIC IMAGING COMMUNITY.
NEW UNDERSTANDING HAS BEEN
GAINED.
WE HAVE MAJOR WORK TO DO WITH
REGULATORY ORGANIZATIONS
INCLUDING PATIENT ADVOCACY
GROUPS AND THE PEDIATRIC
PULMONARY IMAGING AND ADULT
COMMUNITIES.
THERE IS A LARGE PIPELINE OF
MEDICATIONS FORTHCOMING THAT
COULD HELP CHILDREN.
SOME DESIGNS COULD BE HELPFUL
AND VALIDATED SOME OF THOSE
ASSUMPTIONS VALIDATED IN EUROPE.
WE HAVE MAJOR WORK TO DO TO
THINK ABOUT DIFFERENCES IN ADULT
AND PEDIATRICS.
SO SOME OF THESE BAYESIAN
ANALYSIS, PEOPLE CAN FEEL
COMFORTABLE WE ARE COMPARING THE
RIGHT GROUPS.
I SAID IN MY SLIDE THE FIRST
PEDIATRIC INDICATION QUESTION
MARK BECAUSE THAT WAS BREAKING
NEWS LAST WEEK AND NOW A WE HAV
THAT.
NEXT.
SO I WANT TO THANK THE CHILD
FOUNDATION AND ALL THE FAMILIES
THAT ARE A PART OF OUR RESEARCH
NETWORK THAT HELP US THINK ABOUT
THIS EVERY DAY.
THERE WAS ASOUS AMOUNT OF
COLLABORATION.
I WANT TO THANK
BE-INGELHEIM FORG
FAITH IN US.
WITH THAT, I WILL END.
>> THANK YOU, ROBIN.
>> FINALLY, WE WILL TURN TO
KAREN SCHNEIDER WHO IS GOING TO
HELP TALKLP US ABOUTOME
THINGS THAT ARE MAYBE THE
CLINICIAN RESEARCHERS OF US MAY
KIND OF, I DON'T KNOW, DRAW AWAY
FROM THIS TOPIC.
SO I'M GLAD WE HAVE SOMEBODY TO
CHAT MORE AND HIP US THINK ABOUT
THIS PART OF THINGS.
THANK YOU, KAREN.
>> YES, KATELYN.
CAN YOU HEAR ME?
OKAY.
GREAT.
YEAH.
AS KATELYN SAID, I HAVE BEEN ANT
ASR ASSO.
BEFORE THAT I WAS -- I DID WORK
AT UNIVERSITY TECH TRANSFER
DURING LAW SCHOOL AND BEFORE
THAT I WAS A LAB SCIENTIST.
I'M PARTICULA SYMPATHETIC TO SG
PROCESS CAN CAUSE.
I MAKE EVERYONE WHO SENDS MY
SLIDES PUT IN THIS DISCLAIMER,
MY STATEMENTS AND OPINIONS ARE
MY OWN AND MAY NOT REFLECT MY
EMPLOYER.
I'M GOING TO TALK SPECIFICALLY
ABOUT INVESTIGATOR-INITIATED
CLINICAL TRIAL CONTRACTING.
IF THERE ARE QUESTIONS ABOUT
CLINICAL TRIAL CONTRACTING
GENERALLY, THAT COULD BE FOR THE
Q&A.
WE ARE TALKING ABOUT CLINICAL
TRIALS DEVELOPED DESIGNED AND
CONDUCTED WITH AN INVESTIGATOR
WITHOUT PARTICIPATION OTHER THAN
CERTAIN REVIEW AND APPROVAL
RATES OF THE COMPANY SUPPORTER.
THE INVESTIGATOR CAN REQUEST
DRUG FUNDING OR BOTH FROM
PHARMACEUTICAL COMPANY.
OR FUNDING FOR A
NONINTERVENTIONAL STUDY.
I'M GOING TO TALK MORE ABOUT
INTERVENTIONAL STUDIES.
THE INVESTIGATOR IS THE
REGULATORY SPONS AND FULFILLS
ALL OF THOSE OBLIGATIONS AS SET
FORTH IN THE CLINICAL TRIAL
REGULATIONS.
RESPONSIBLE FOR ALL OF THE
CONDUCT MONITORING SAFETY
RECORDING DATA ANALYSIS
OBLIGATIONS OF ANY STUDY
SPONSOR.
TYPICALLY A DRUG COMPANY WILL
HAVE ON ITS WEBSITE INSTRUCTIONS
FOR SUBMITTING A REQUEST FOR
SUPPORT AND THERE WILL BE
INFORMATION ABOUT THE COMPANY'S
RESEARCH AREAS O INTEREST.
BECAUSE THE COMPANY IS GOING TO
SUPPORT STUDIES THAT ALIGN WITH
ITS OWN RESEARCH INTERESTS.
MIGHT HELP INFORM THE USE OF THE
DRUG AND ALSO ADDRESS AN UNMET
MEDICAL NEED.
GO TO THE NEXT SLIDE.
WE HEA A LOT ABOUT THE BARRIERS
THAT EXIST WITHIN CONTRACTING.
MYRA ONE TIP IS ALWAYS GET
ON THE PHONE.
I COULD PROBABLY TALK FOR 20
MINUTES ABOUT THE FRUSTRATIONS.
THESE DAYS IT IS EASY TO GO BACK
AND FORTH IN COMMENTS AND THE
WORD DOCUMENT AND NEGOTIATE THAT
WAY.
THAT WILL TAKE MORE TIME THAN
GETTING ON THE PHONE.
I ALWAYS RECOMMEND THE
INVESTIGATOR JOINS THE CALL.
THAT WAY THE PARTIES ARE ALIGNED
AND YOU DON'T NEED A SECOND
CALL.
THE CONTRACT IS INTENDED TO
PROTECT BOTH PARTIES, DEFINE THE
ROLES AND RESPONSIBILITIES OF
EACH PARTY.
THAT INCLUDES THE CONDUCT OF THE
STUDY, THE SAFETY REPORTING
OBLIGATIONS, ANY REVIEW RIGHTS
THAT THE COMPANY MIGHT HAVE.
SO THAT IS USUALLY LIKE A
MONITORING PLAN OR SAFETY
MANAGEMENT PLAN.
ANY SORT OF PROTOCOL AMENDMENTS
THE COMPANY IS GOING TO REVIEW
THOSE IF THEY ARE SUPPORTING THE
STUDY.
THE CONTRACTEDDRESSES DRUG
SUPPLY.
HOW PAYMENT IS STRUCTURED, WHICH
WE'LL TALK ABOUT A LITTLE BIT
LATER.
BUT IT IS IMPORTANT THAT BOTH
PARTIES WHO ARE NEGOTIATING
UNDERSTAND THE GOALS FOR THE
STUDY.
I THINK FOR INVESTIGATOR
INITIATED TRIALS THE BIGGEST
ISSUE IS THAT THEY ARE GENERALLY
LESS COMMON THAN COMPANY
SPONSORED TRIALS.
IF A NEGOTIATOR ON EITHER SIDE
DUNCE UNDERSTAND THE DIFFERENCE
IN WHAT WE LOOK FOR THAT CAN
CAUSE DELAYS.
I HAVE PROBABLY DONE ABOUT 100
INVESTIGATOR INITIATED CONTRACTS
VERSUS THOUSANDS AND THOUSANDS
OF COMPANY SPONSORED CONTRACTS.
THE DRUG COMPANY PROVIDES THE
TEMPLATE 80% OF THE TIME.
THAT TEMPLATE ALLOWS FOR
FLEXIBILITY FOR DIFFERENT TYPES
OF STUDY STRUCTURES, IT IS GOOD
TO PLAN AHEAD FOR A TEMPLATE
THAT ALLOWS YOU TO FIT THE STUDY
YOU ARE NEGOTIATING FOR.
SO WHAT WE HEAR FROM
INVESTIGATORS IS THAT THE FOCUS
REALLY IS ON PATIENT CARE AND
SCIENTIFIC ADVANCEMENT.
THERE IS AN INTEREST FOR BOTH
SIDES IN THE INVESTIGATOR
PUBLISHING THE STUDY.
WHERE WE GET STUCK WHICH I WILL
TALK ABOUT ON THE NEXT SLIDE IS
THE AREAS OF FOCUS ON
NEGOTIATION COME DOWN TO
INTELLECTUAL PROPERTY, MAKING
SURE THE COMPANY HAS ACCESS TO
THE DATA AND THE LIABILITY AND
RESPONSIBILITY OBLIGATIONS FIT
THE TYPE OF STUDY WE ARE
NEGOTIATING FOR.
SO YOU CAN GO TO THE NEXT SLIDE.
SO I COULD PROBABLY TALK FOR 20
MINUTES ABOUT INTELLECTUAL
PROPERTY PROVISIONS IN
CONTRACTS, BUT I THINK THE BIG
TAKEAWAY IS THAT THE COMPANY
DOESN'T FEEL LIKE THEY ARE BEING
BLOCKED FROM POTENTIAL
INVENTIONS THAT ARE AN
IMPROVEMENT OR THE USE OF T
Y E INVESTED SO MUCH
TIME AND MONEY INTO.
AND I THINK THE MOST COMMON WAY
TO STRUCTURE THIS CONTRACTUALLY
IS TO STUDY DRUG IP SEPARATED
OUT FROM OTHER IP.
AS LONG AS THE COMPANY FEELS
LIKE THEY HAVE OWNERSHIP RIGHTS
OR EXCLUSIVITY TO THOSE STUDY
DRUG RELATED INVENTIONS THERE IS
GENERALLY A PATH FORWARD.
AND THIS IS ANOTHER REASON TO
PICK UP THE PHONE AND MAKE SURE
WE ARE ALIGNED ON THE INTERESTS
OF BOTH PARTIES.
THE BIG, ONE OF THE BIG
DIFFERENCES BETWEEN
INVESTIGATOR-INITIATED TRIAL
CONTRACTS AND COMPANY-SPONSORED
TRIAL CONTRACTS IS THE LIABILITY
PROVISION, RIGHT?
I HAVE SEEN A LOT OF CONTRACT
NEGOTIATIONS WHERE THE SPONSOR
INSTITUTION IS ASKING FOR
LIABILITY TERMS THAT ARE SIMILAR
COMPANY-SPONSORED CONTRACTSRE
MEANING THEY ARE ASKING THE
COMPANY WHO ME SUPPORTING
THE STUDY TO EITHER PROVIDE
INSURANCE OR BE LIABLE FOR
SUBJECT INJURY.
FOR AN INVESTIGATOR-INITIATED
TRIAL WHERE THE COMPANY IS NOT
CONTROLLING THE DESIG OR
CONDUCT, TYPICALLY THE MOST IN
TERMSINDEMNIFICATION
RELIABILITY WE CAN PROVIDE IS
ANY INJURY CAUSED BY MAYBE
MANUFACTURING DEFECTS OR
LABELING DEFECTS TO THE DRUG.
THE ACCESS TO THE DATA IS REALLY
KEY.
I'VE SEEN COMPANIES ASK FOR
REGULAR REPORTS, QUARTERLY
REPORTS ON THE STATUS OF THE
TRIAL AND THE COMPANY AND THE
SPONSOR W DETERMINE TOGETHER
WHAT THE SAFETY REPORTING LOOKS
LIKE.
IT I A BIG PART OF THE
CONTRACT.
ACCESS TO DATA IS BIG.
THERE ARE SOME COUNTRIES WHERE
THE COMPANY WOULD HAVE TO PAY AN
ADDITIONAL FEE OR LICENSE THE
DATA.
AND THOSE COUNTRIES ARE
TYPICALLY AVOIDED IN
INVESTIGATOR-INITIATED TRIAL
SUPPORT ON THE COMPANY SIDE.
TERMINATION OBLIGATIONS ARE
ANOTHER CONSIDERATION FOR DRUG
COMPANIES.
BOTH, I THINK BOTH THE SPONSOR
AND THE COMPANIES ARE ALIGNED
THAT THE TRIAL MIGHT BE
TERMINATED FOR SAFETY REASONS OR
POTENTIALLY FOR RFUTIR BUT
SOMETIMES SUPPLY CONSIDERATIONS
COME INTO PLAY.
IF THE COMPANY NO LONGER
MANUFACTURING A DRUG, THEY ARE
PROBABLY NOT GOING TO
MANUFACTURE THE DRUG
SPECIFICALLY FOR THE
INVESTIGATOR-INITIATED TRIAL.
I THINK, YOU KNOW, SOMETIMES
ENROLLMENT JUST DOESN'T HAPPEN
THE WAY THAT THE SPONSOR
INTENDED.
SO, YOU KNOW, WITH FUNDING TIED
TO ENROLLMENT, SOMETIMES A
COMPANY MIGHT NEED TO EXERCISE
TERMINATION RIGHTS BECAUSE OF
TIME LIMITS AND ENROLLMENT.
I HAVE BEEN INVOLVED WITH TRIALS
THAT INVOLVED MORE THAN ONE DRUG
COMPANY.
IT MIGHT BE A STUDY DESIGNED
WITH MULTIPLE ARMS.
FOR CONTRACTING, I WOULD
RECOMMEND THAT BOTH OR MORE THAN
TWO DRUG COMPANIES ALIGN FIRST
NEGOTIATING WITH THE
SPONSOR INSTITUTION.
TYPICALLY A SMALLER COMPANY
WOULD BE HAPPY TO USE THE
CONTRACT FOR A LARGER COMPANY SO
LET THEM SORT OFOR ALIGN FIRST.
IF EVERYONE IS CONTRACTING
SEPARATELY, THE MAIN THING I
LOOK FOR ISHAT THE
INSTITUTION, THE SPONSOR
INSTITUTION IS GOING TO BE ABLE
TO REPRESENT THE IP TERMS,
INTELLECTUAL PROPERTY TERMS FOR
ALL PARTIES ARE ALIGNED AND
CONSISTENT AND NEITHER COMPANY
IS GOING TO HAVE MORE FAVORABLE
OR QUICKER TRANSMISSION OF THE
DATA.
SO WE WOULDN'T WANT ANOTHER
COMPANY KNOWING ABOUT THE DATA
BEFORE WE DO.
SO FOR INVESTIGATOR-INITIATED
TRIALS THAT THE COMPANY IS
SUPPORTING WITH FUNDING, WE
TYPICALLY SEE THE BUDGET
STRUCTURE, THE PAYMENT TERMS
THAT ARE MILESTONE BASED AND
TYPICALLY FOR ENROLLMENT.
SO WE MIGHT SEE THE FIRST
PAYMENT BE -- DUE AFTER CONTRACT
EXECUTION AND SEVERAL ENROLLMENT
BASED MILESTONES.
TYPICALLY THE LAST MILESTONE
PAYMENT WILL BE PAID OUT AFTER
COMPLETION OF THE FINAL REPORT
OR A MANUSCRIPT SUBMISSION.
ONE THING I LIKE TO HIGHLIGHT IS
WHERE YOU ARE TALKING ABOUT AN
INVESTIGATOR INITIATED TRIAL AND
THE COMPANY IS ARM'S LENGTH, I
RECOMMEND A LINE ITEM FOR
PUBLICATION SUPPORT.
I HAVE SEEN REQUESTS FOR
PUBLICATION SUPPORT COME AFTER
THE DATA HAS BEEN GENERATED AND
I THINK THAT THE COMPANY IS MUCH
LESS LIKELY TO SUPPORT PAY FOR
PUBLICATION AFTER THE FACT SO IT
DOESN'T LOOK LIKE MAYBE THEY ARE
PAYING JUST FOR GOOD DATA.
NEXT SLIDE.
SO IT IS PRETTY COMMON FOR A
SPONSOR INVESTIGATOR TO BRING ON
SUB SITES, ESPECIALLY IN A RARE
DISEASE SPACE WHERE THERE ARE
ENROLLMENT LIMITATIONS AT A
PARTICULAR SITE.
TYPICALLY THE DRUG COMPANY
DOESN'T GET INVOLVED AT ALL WITH
CONTRACTING FOR SUB SITES.
WE LOOK FOR REPRESENTATION THAT
THE SPONSOR INSTITUTION IS GOING
TO ENSURE THAT ANY SUB SITE
COMPLIES WITH THE SAME TERMS AS
OUR CONTRACT.
SO THAT IS ALL SORT OF DONE
BEHIND THE SCENES AND IF THERE
ARE ANY ISSUES WE GO DIRECTLY TO
THE SPONSOR.
WE, AS A SPONSOR -- SORRY, WE AS
THE DRUG MANUFACTURE MIGHT AGREE
TO SHIP THE DRUG TO SUB SITES
AND THAT CAN BE WORKED OUT IN
THE CONTRACT.
USUALLY THERE IS A DRUG SUPPLY
FORM WE ATTACH AS AN APPENDIX.
WE ARE ALIGNED ON WHAT THAT FORM
LOOKS LIKE AND HOW WE GET DRUG
TO THE VARIOUS SUB SITES.
I MENTIONED EARLIER THERE ARE
SOME COUNTRIES THAT MIGHT NOT
WORK TO HAVE SUB SITES IN.
SEVERAL EUROPEAN COUNTRIES
WOULDN'T BE ABLE TO AGREE TO THE
TERMS THAT A COMPANY REQUIRES IN
TERMS OF LICENSING OR ASSIGNMENT
OF INTELLECTUAL PROPERTY AND
ALSO THE ACCESS TO THE DATA.
SO WE MIGHT BE ABLE TO GET A
HIGH LEVEL SUMMARY, BUT IN TERMS
OF ACCESS DATA WE WOULD HAVE
PAY FOR THAT, WHICH TYPICALLY
CANNOTE NEGOTIATED UPFRONT.
BECAUSE THE VALUE OF THE DATA OR
THE INVENTION CAN'T BE
PREDETERMINED.
SO COMPANIES FOR THE MOST PART
STAY AWAY FROM SUPPORTING
INVESTIGATOR-INITIATED STUDIES
IN THOSE COUNTRIES WHERE THOSE
RESTRICTIONS EXIST.
SO I THINK IT IS IMPORTANT TO
UNDERSTAND WHERE THERS POTENTIA
SUB SITES ALSO MIGHT BE FROM THE
SPONSOR AT THE GET-GO TO MAKE
SURE WE ARE NOT GOING TO HAVE
ANY ISSUES WITH SUB SITES COME
PLYI II IING -- COMPLYING WITH
TERMS OF THE CONTRACT.
I THINK THAT IS THE LAST SLIDE.
>> THANK YOU, KAREN.
>> YEAH.
>> SO IF WE CAN GO AHEAD AND
HAVE ALL OF OUR SPEAKERS FROM
SESSION 4 TURN ON YOUR CAMERAS
SO YOU CAN BE PRESENT FOR
QUESTIONS.
THEY WILL HIGHLIGHT US SO WE ARE
ONLY THE ONES SEEN TALKING.
AND REMINDER TO EVERYBODY TO PUT
QUESTIONS IN THE Q&ABOX.
WE DEFINITELY HAVE SOME WE CAN
GOAD AND GET STARTED WITH.
FIRST OF ALL, THANK YOU.
IT IS A NICE PICTURE WE HAVE
PAINTED OVER THE MORNING FROM
SPECIAL CONSIDERATIONS TO
ACTUALLY THINKING ABOUT HOW TO
DESIGN A TRIAL TO, HEY, WE DID
THIS TRIAL, THIS IS WHAT WE
LEARNED AND THE IMPORTANT WORK
THAT YOU ARE DOING ON THE BACK
END, KAREN, OF MAKING SURE THAT
ALL THE CONTRACTS LANGUAGE COMES
TOGETHER SO IT IS ACTUALLY
SUCCESSFUL.
SO I WILL GO AHEAD AND START
WITH SOME OF THE QUESTIONS IN
THE CHAT AND CERTAINLY MORE CAN
COME IN.
JEFF MOFFIT BROUGHT UP THE
UPCOMING APPROVAL OF NURANDOMA
LARKS AST, WHICH I'M PROBABLY
NOT SAYING RIGHT, A NEW DRUG
COMING TO THE MARKET FOR
IDIOPATHIC FIBROSIS.
DOES THAT CHANGE HOW WE ARE
THINKING OF NINTEDANIB IN
CHILDREN AND HOW DO WE THINK
ABOUT THIS CONCEPT MORE
GENERALLY?
NEW APPROVAL THAT MAY REBALANCE
THAT CLINICAL RISK BENEFIT.
>> I ASSUME THAT IS MY QUESTION?
>> YEAH.
I THINK SO.
SO THERE IS A LOT OF PIPELINE
POTENTIAL DRUG.
NOT EVERYTHING MAKES IT THROUGH
PHASE 3.
THAT IS AH PLAN TO APPROACH OUR
COMMUNITY AGAIN.
ONE OF THE THINGS ABOUT THE EMA
APPROVAL IS WE HAVE AT LEAST A
STARTING PLACE FOR A DESIGN TO
THINK ABOUT ONE THAT WAS
SUCCESSFUL.
THERE COULD BE MODIFICATIONS TO
THAT.
BUT WE HAVE A STARTING PLACE TO
BE ABLE TO THINK ABOUT STUDYING
THIS OTHER MEDICATION.
THERE ARE MANY THINGS TO THINK
ABOUT AS NEW DRUGS COME FORWARD
IN THE ADULT PIPELINE.
WE STILL HAVE A LIMITED NUMBER
OF PATIENTS.
SO HOW DO YOU CHOOSE WHICH
DRUGS?
HOW DO YOU INCLUDE -- DO THEY
GET TO BE ON NINTEDANIB?
DO YOU CHOOSE MANY IN THE
CLINICAL REALM?
DO YOU CHOOSE NINTEDANIB -- HAS
AN INDICATION.
ARE YOU GOING TO DO OFF LABEL?
OUR COMMUNITY WILL BE APPROACHED
BECAUSE THERE WILL BE PEPS
INVESTAL PLANS.
WE HAVE TO THINK OF THE SIZE OF
OUR COMMUNITY, HOW WE DESIGN
THESE TRIALS.
DID WE LEARN THINGS THAT MAKE
THE NEXT TRIAL EASIER?
I THINK WE DID, I THINK WE HAVE
AND ARE WORKING QUICKLY TO
ESTABLISH SOME OF THOSE
ASSUMPTIONS.
WE HAVE REGULATORY WORK TO DO
WITH THE FDA.
NINTEDANIB'S PATHWAY FORWARD,
THAT WAS A FINAL LETTER FROM THE
FDA.
SO NEW DRUG MEDICATIONS STUDIES
WILL HOPEFULLY OPEN PATHWAYS TO
THE FDA.
AND THAT PROCESS, THAT WE CAN
HAVE BROADER CONVERSATIONS.
>> AND I WANTED TO FOLLOW UP TO
THE EXTENT YOU CAN SHARE YOUR
INSIGHTS INTO WHY THE APPROVAL
FROM THE EMA VERSUS THE FDA AND
I KNOW YOU CAN'T SHARE SOME
SPECIFIC
SPECI
SPECIFICS, HOW MIGHT YOUR
APPROACH BE DIFFERENT IN TRIAL
DEVELOPMENT?
>> I'M ALWAYS NERVOUS WHAT I CAN
SAY AND CAN'T SAY.
WE HAD FOLLOW-UP CONVERSATIONS
WITH MEMBERS OF THE FDA.
WE HAVE WORK TO DO IN THINKING
ABOUT PEDIATRICS AND ADULTS.
BAYESIAN ANALYSIS, WE BORROWED
THE POPULATION FROM THE ADULT
STUDIES.
WHAT IS THE BEST GROUP OF ADULT
PATIENTS TO BORROW FROM?
PROBABLY NOT IPF, BUT THERE ARE
OTHERS.
SO HOW DO WE REFINE OUR
CONVERSATIONS ABOUT MAKING
COMPARISONS TO THE ADULT
POPULATION?
HOW DO WE DO RESEARCH TO LOOK AT
HOW DOES PEDIATRIC FIBROSIS
COMPARE TO ADULT FIBROSIS.
NOW IT IS A CRITICAL QUESTION TO
BRING THESE TRIALS FORWARD.
I BELIEVE MYSELF THE MECHANISM
OF DISEASE WITH FIBROSIS, THOSE
PATHWAYS ARE STILL ACTIVE IN
KIDS AND ADULTS, BUT THE
BACKGROUND OF DEVELOPMENT IS
IMPORTANT.
THINKING DEVELOPMENTALLY ABOUT
THIS.
THERE ARE A LOT OF QUESTIONS
THAT CAN BE ASKED IN BASIC
SCIENCE AND TRANSLATIONAL ARENA
THAT ARE NOW CRITICAL BECAUSE
THEY ARE GOING TO BE IMPORTANT
FOR US GETTING TREATMENT TO
KIDS.
IMAGING PATHOLOGIC CORRELATION
TO VALIDATE CT CRITERIA ARE
STUDIES UNDER WAY.
I THINK THE FDA WANTS TO SEE
SOME OF THAT TO UNDERSTAND THOSE
DIFFERENCES.
AND WE -- THE PATIENT COMMUNITY
MAYBE NEEDS TO BE MORE ACTIVE
ABOUT WE NEED THESE DRUGS.
HOW SAFE DO YOU WANT TO BE
COMPARED TO GETTING DRUGS TO
KIDS OR NOT GETTING DRUGS TO
KIDS THAT ARE DYING FROM THIS?
WHAT IS THE RISK BENEFIT RATIO
WE CAN TALK ABOUT?
THERE IS ADVOCACY WORK.
SCIENTIFIC INVESTIGATIONS WORK
THAT WILL NEED TO COME FORWARD.
AND NOW THERE WILL BE DIFFERENT
CONVERSATIONS NOW THE DESIGN HAS
BEEN AT LEAST VALIDATED IN
EUROPE.
BUT I'M OPEN.
I HAVE EXPERTS ON THE LINE THAT
COULD TAKE US FURTHER WITH
INSIGHTS SO I APPRECIATE THAT.
>> DORIS, FROM YOUR PERSPECTIVE
AS A CONSULTANT IN THIS SPACE,
WHEN YOU ARE WORKING WITH SOME
OF US MAYBE IN THE ROOM OR
TRYING TO THINK ABOUT HOW IF WE
NEED TO LAY THE GROUNDWORK FOR
THE END POINTS WE ARE USING FOR
STUDIES FOR RARE LUNG DISEASE IN
KIDS WHAT FACTORS DO WE NEED TO
CONSIDER WHEN WE THINK ABOUT
EVENTUALLY GETTING FDA APPROVAL?
>> YEAH.
THAT IS A REALLY GOOD QUESTION.
I WORKED WITH JEFF IN AN
INSTANCE WHERE WE WERE THINKING
ABOUT THIS.
I THINK ONE OF THE THINGS THAT I
ALWAYS ENCOURAGE MY CLIENTS IS
WE THINK ABOUT WHAT IS YOUR
IDEAL LABEL, RIGHT?
AND WHAT IS THAT FIRST
POPULATION YOU MIGHT BE YOUR
OPPORTUNITY FOR APPROVAL?
AND THEN WHAT WOULD BE THOSE
APPROVAL END POINTS?
I ALWAYS LIKE TO HAVE THE WORD
PLURAL SO YOU HAVE IN YOUR BACK
POCKET THESE ARE THE THREE
THINGS THAT COULD POTENTIALLY BE
THE END POINTS THAT WE USE FOR
APPROVAL.
IF THERE IS ANY WAY YOU CAN BAKE
THEM IN YOUR PHASE 1 TRIAL EVEN
IF IT EXPLORATORY TO FIGURE OUT
HOW TO GATHER DATA, TO ME, I
THINK THAT IS REALLY IMPORTANT.
DOES THAT ANSWER YOUR QUESTION?
>> YEAH.
IT CERTAINLY HELPS US HAVE THE
CONVERSATION.
IT SEEMS LIKE THIS IS GOING TO
BE AN ONGOING CONVERSATION FOR
OUR COMMUNITY.
ROBIN, JEN ASKED APPROPRIATELY,
CAN YOU TALK ABOUT PATIENT
RECRUITMENT GIVEN THE RARE
NATURE OF THESE DISEASES?
>> I DIDN'T GET INTO DETAIL, BUT
THERE IS A VERY COMPLICATED
STUDY FOR OUR COMMUNITY.
THERE WERE ANIMAL STUDY CONCERNS
ABOUT TEETH DEVELOPMENT, BONE
DEVELOPMENT.
SO THIS STUDY DESIGN INCLUDED
IMAGING OF THE TEETH, LONG BONE
MRIs AND SO IN ADDITION TO
HAVING A RARE COMMUNITY, IT
COMPLICATED A LOT OF VISITS.
MY HOPE IS THE NEXT STUDIES
AREN'T AS COMPLICATED.
I THINK THE COMMUNITY WAS A
LITTLE HESITANT.
THIS WAS A VERY SICK POPULATION
SO THESE PATIENTS WHO CAME
FORWARD CAME FORWARD BECAUSE
THEY WERE SICK.
THERE WERE STILL HESITATIONS TO
ENROLL.
I THINK THIS ALSO HAS GIVEN
HOPEFULLY SOME OF THE PATIENTS
CONFIDENCE THAT WE CAN DO THIS.
THE SPONSOR PAID FOR PATIENTS TO
FLY IN.
SO PATIENTS FLEW IN TO PRIMARY
STUDIES AND ALL OF THAT WAS PAID
FOR SO THEY COULD FLY IN EVEN
THOUGH IT WAS FREQUENT.
THE PATIENTS MADE COMMITMENTS TO
FLY INTO CENTERS DOING THIS
STUDY TO GET ACCESS TO THIS
DRUG.
SO SOME OF THIS INFORMATION THE
PATIENT ORGANIZATIONS WILL BE
HELPFUL TO UNDERSTAND.
I THINK HAVING RARE DISEASE HAVE
ACCESS TO STUDY CENTERS, IT WILL
TAKE ABILITY TO GET THOSE
PATIENTS TO THOSE CENTERS TO
PARTICIPATE.
>> RELATED TO PICKING OUR
PATIENTS FOR CLINICAL TRIALS,
QUESTION DIRECTED AT KAREN, BUT
IMPORTANT TO CONSIDER.
SO IS THAT PATIENT ENROLLMENT
CRITERIA TYPICALLY CO-DEFINED
BETWEEN INVESTIGATOR AND THE
COMPANY?
DOES THE INNOVATOR COMPANY
ENGAGE WITH THE PARTNERS AND
INVESTIGATOR ON AN ONGOING
BASIS?
HOW DOES THAT AGREEMENT COME
INTO PLAY FROM A CONTRACT
STANDPOINT?
>> YEAH.
I THINK FOR
INVESTIGATOR-INITIATED STUDIES,
IT IS GOING TO BE THE PROPOSAL
THAT COMES FROM THE INVESTIGATOR
SPONSOR.
AND SO AS LONG AS IT MAKES SENSE
TO THE COMPANY PROVIDING SUPPORT
THEN THAT'S GOING TO BE HOW IT
IS WRITTEN IN THE CONTRACT.
OBVI
OBVIOUSLY, IT IS A DIFFERENT
SITUATION FOR A
COMPANY-SPONSORED TRIAL SO A
COMPANY CAN MAKE THOSE
DETERMINATIONS WITH THE HELP OF
THOSE ADVISERS.
>> WE ALSO JUST TALKING ABOUT
CONTRACTS, DR. McCORMACK NOTED
THAT TRIALS AT THEIR FACILITIES
ARE RATE LIMITING STEP, THE
CONTRACTING SEEMS TO BE A RATE
LIMITING STEP AND LEGAL TEAM IS
STRETCHED PRETTY THIN ACROSS THE
UNIVERSITY.
SO ARE THERE PLACES THAT HAVE
DEDICATED LEGAL COUNSEL FOR
TRIALS IN PARTICULAR THAT YOU
KNOW OF?
ARE WE ABLE TO SHOW THAT IS
FINANCIALLY FEASIBLE FOR OUR
INSTITUTIONS?
>> YEAH.
IT'S TYPICALLY THERE'S A
CLINICAL TRIALS OFFICE THAT
HANDLES CONTRACTING AT
INSTITUTIONS.
IT IS A VERY DIFFERENT SET OF
PRIORITIES I THINK FOR A COMPANY
LIKE MINE IT IS SORT OF WHAT IS
IMPORTANT TO THE COMPANY, RIGHT?
AND THEN, YOU KNOW, WE ARE SORT
OF MOTIVATED A LITTLE BIT
DIFFERENTLY TO MAYBE PULL AN
ALL-NIGHTER IF YOU HAVE TO, BUT
THAT IS NOT THE CULTURE AT
UNIVERSITY OFFICES.
SO I THINK WHAT UNIVERSITY
OFFICES IN MY EXPERIENCE REACT
TO IS THE SQUEAKY WHEEL, RIGHT?
THE INVESTIGATOR WHO IS MAKING
THE CALLS, WHO IS REALLY
ADVOCATING FOR THE STUDY.
WHEN WE NEED SOMETHING MOVED
ALONG, WE GET THE INVESTIGATOR
INVOLVED BECAUSE THE UNIVERSITY
LEGAL OFFICE DOES NOT CARE WHAT
I HAVE TO SAY.
THEY CARE MORE ABOUT THEIR OWN
INVESTIGATORS.
>> ONE QUESTION THAT REALLY IS
OPEN TO ANYBODY, REALLY, IN THE
ENTIRE SPACE.
SO IF YOU HAVE -- TALK ABOUT
THAT PROCESS OF HAVING AN
INVESTIGATOR-INITIATED IND AND
IF THERE IS COMMERCIAL INTEREST
HOW THAT BECOMES COMMERCIALLY
SUPPORTED IND IF A COMPANY
BECOMES INTERESTED MID TRIAL.
LIKE YOU ARE ALREADY DOING THE
BASIC WORK.
>> I CAN JUST COMMENT ON ONE
SCENARIO.
I HAVE SEEN IN THE PAST AN
INVESTIGATOR INITIATED PROTOCOL
BECOME A COMPANY-SPONSORED
PROTOCOL.
IT WAS SET UP ALMOST LIKE A
PURCHASE.
PAYING FOR THE SERVICES OF
PROTOCOL DEVELOPMENT.
I HAVE SEEN THAT HAPPEN.
AND IT IS POSSIBLE.
YOU CAN DO ANYTHING THROUGH
CONTRACTING, I ALWAYS SAY.
THAT WAS JUST MY OWN EXPERIENCE.
>> SO IN MY EXPERIENCE, I HAVE
WORKED IN A COUPLE OF SCENARIOS
AND RECENTLY HAD A CLIENT THAT
WAS I.T. AND INSTEAD OF -- THEY
DID A COMPANY SPINOFF TO START
THE PHASE 2 TRIAL AND WE JUST
DID A FRESH NEW IND TO KEEP
EVERYTHING CLEAN AND CROSS
REFERENCED THE IND.
CAN'T SPEAK TO THE CONTRACTING
SIDE.
THE OTHER STRATEGY I HAVE USED
THAT HAS WORKED REALLY WELL IS A
HYBRID IIT, MAYBE THE DRUG
DEVELOPER INTERESTED MAY HOLD
THE IND OR MAYBE THEY ARE MORE
HEAVILY INVOLVE SOD THE ELEMENT
OF DATA HAVING IT IN -- FORMAT
AND ALL OF THAT, SAFETY, SOME OF
THOSE ELEMENTS CAN BE ROLLED IN.
I WORKED WITH A CLIENT WHERE WE
DID A HYBRID IIT.
WE CONVERTED THAT PHASE 1 TRIAL
INTO A PIVOTAL TRIAL BECAUSE IT
WAS SO -- WE HAD 100% RESPONSE
RATE OF THE PATIENTS.
AND IT WAS A RARE DISEASE.
SO I GUESS MAYBE MY POINT IS
WHEN I TALK TO MY CLIENTS THERE
ARE OPTIONS AND IT IS ALWAYS
GOOD TO KIND OF PUT YOUR STICKY
NOTE FROM THE WALL AND SEE WHAT
THE OPTIONS ARE TO SEE WHAT
STRATEGY IS GOING TO WORK THE
BEST.
>> THAT IS ACTUALLY A REALLY
GOOD POINT, DORIS.
WE HAVE OTHER OPTIONS OTHER THAN
COMPANY-SPONSORED TRIALS AND
INVESTIGATOR-INITIATED TRIALS.
WE CALL IT COLLABORATIVE.
YOU CAN CALL IT WHATEVER YOU
WANT IT LOOKS IN BETWEEN.
IT IS FOR THE PARTIES TO DECIDE
WHAT THE ROLES AND
RESPONSIBILITIES ARE.
WE WOULD CALL THAT COLLABORATIVE
RESEARCH.
>> I DEFINITELY WANT TO GET BACK
TO TALKING SOME ABOUT END POINTS
BECAUSE WE HAVE SOME QUESTIONS
IN THE CHAT ABOUT THAT.
I ALSO WANT TO GO BACK TO THAT
FIRST TALK THAT WE HAD, JEN, YOU
TALKED ABOUT SOME OF THE
BARRIERS YOU SEE FROM BRINGING
TREATMENTS TO INFANTS.
AND YOU HAVE THIS WONDERFUL LIST
OF CONSIDERATIONS WE AS A
COMMUNITY NEED TO THINK ABOUT TO
MAKE THIS HAPPEN.
INCLUDING PROVIDER EDUCATION,
ACCESS TO GENETIC TESTING.
HOW DO WE GET PEOPLE TO THE
CENTERS OF EXPERTISE AND
COLLABORATE WITH NEONATOLOGY.
IF I HAD TO FORCE YOU TO PICK
ONE OR TWO THINGS OUR COMMUNITY
SHOULD BE FOCUSED ON, WHAT IS
THAT SPACE FOR YOU?
>> IT IS A GREAT QUESTION.
I THINK ACCESS TO GENETIC
TESTING WOULD BE THE TOP
PRIORITY.
WE ARE WORKING ON A NEW AMERICAN
TH
THORACI STUDY STATEMENT.
WITH THAT WE ARE HOPEFUL THERE
WILL BE RECOMMENDATIONS ABOUT
GENETIC TESTING IN INFANTS AND
CHILDREN.
HOPEFULLY GETTING THE DIAGNOSES
SOONER.
WAS THE DIAGNOSIS IS MADE AND
SOMETIMES THAT IS COMPLICATED,
BUT IN GENERAL, PEOPLE CAN REACH
OUT TO THEIR PULMONOLOGIST AT
THEIR CENTER WHO MAYBE IF THEY
ARE NOT AN EXPERT IN ILD CAN
CONNECT TO SOMEONE WHO IS.
CONTINUING TO HAVE A PRESENCE AT
NATIONAL MEETINGS, CONTINUING TO
TALK ABOUT DIAGNOSIS AND
UPCOMING THERAPIES TO GENERATE
AWARENESS AND RECOGNITION I
THINK IS REALLY IMPORTANT.
>> IF WE CAN'T FIND THE PATIENTS
WE CAN'T HELP THE PATIENTS,
RIGHT?
>> CORRECT.
>> I JUST WANTED TO ADD BECAUSE
JEN IS TALKING ABOUT THOSE
YOUNGER PEDIATRIC PATIENTS.
THINKING ABOUT VULNERABLE GROUPS
IN THE PEDIATRIC POPULATION
CREATES A SPECIAL TASK RELATED
TO END POINTS.
THE REGULATORY AGENCIES LIKE
TRADITIONAL END POINTS,
PULMONARY FUNCTIONING TEST,
CAPACITY IN FIBROSIS.
I WOULD SAY WE DO HAVE SOME
EVOLVING DATA THAT IN GROWING
CHILDREN WITH LUNG FUNCTION THAT
PULMONARY FUNCTIONS MAY NOT BE
THE BEST INDICATOR OF ADVANCING
DISEASE.
IT MAY BE IMAGING WHERE FIBROSIS
IS EVOLVING.
SO THERE IS A LOT WE NEED TO
LEARN ABOUT KIDS.
WE CAN FIT IN WITH TRADITIONAL
APPROACHES.
I'M HOPEFUL WE CAN THINK
BROADER.
YOU SAW THE FAMILIAR SCORE, A
BIG WIN IN THE EUROPEAN.
THE FAN SCORE HAD TO DO WITH
OXYGEN.
PHYSIOLOGIC MEASUREMENTS IN
CHILDREN, JEN IS A
NEONATOLOGIST.
THAT TESTING IS NOT HAPPENING.
HOW DO WE BEGIN TO VALIDATE
THOSE IN CLINICAL TRIALS?
WE ARE GOING TO NEED THAT.
THERE ARE NEW DEVICES AND NEW
WAYS TO THINK ABOUT THIS.
THOSE QUESTIONS NEED TO BE
ASKED.
WE NEED TO BE MORE ASSERTIVE FOR
THE PEDIATRIC GROUP.
MAYBE INDEPENDENT INVESTIGATOR
TRIALS TO ASSESS THAT AS AN
AJUNCTION TO SOME OF THE BIGGER
TRIALS RUNNING FORWARD.
I FEEL STRONGLY WE NEED TO DO
THAT.
I THINK DR. KAITH POSTED SHE
WORKS IN THE SPACE SO LOTS OF
INTEREST IN VALIDATING NEW
STUDIES.
ARE THERE END POINTS BEST
TRANSLATE TO PEDIATRIC
POPULATIONS.
IT IS MORE OF A PHYSIOLOGIC
RESPONSE OR MEASURE TO DISEASE.
IS THERE ANYTHING YOU GUYS HAVE
SEEN IN THE ADULT LITERATURE YOU
THINK WE COULD WORK TOGETHER ON
OR WAYS TO KIND OF, AGAIN,
BORROW FROM THEIR SPACE THAT
MIGHT WORK IN OUR PATIENTS?
THIS IS ONE, TOO, I THINK
ANYBODY CAN UNMUTE THEMSELVES AT
THIS POINT.
WE HAVE A FEW MINUTES.
SO IF THERE ARE PEOPLE WHO
WANTED TO ADD INTO THIS
DISCUSSION VERBALLY, I'M OKAY
WITH THAT THE OTHER PEOPLE HAVE
THOUGHTS ON THIS END POINT
DISCUSSION.
>> I WILL ADD PULSE OX DLERKS
METRY RESPIRATORY RATE, WHICH IS
A HARD ONE TO MEASURE
ACCURATELY, BUT SOME DEVICES ARE
DOING THIS IN A VALIDATED WAY.
POTENTIALLY MOVEMENT OR KIND OF
MOVEMENT-BASED IS A LOT OF
DEVICES NOW THAT ARE LOOKING AT
MOVEMENT.
THAT THESE ARE ALL POTENTIAL
INDICATIONS OF PULMONARY HEALTH
OR HEALTH.
THEY NEED TO BE EXPLORED.
I'M HOPING NHLBI WILL HELP US.
DR. WAMBACH, WHAT DO YOU THINK
OF THAT FOR YOUR BABIES?
WE ARE NOT DOING PFTs
NECESSARILY ON BABIES.
WE DON'T HAVE A WAY TO DO THAT?
>> WE CAN LOOK AT MARKERS OF
VENTILATION, OXYGENATION,
VENTILATOR CHANGING OVER TIME,
LOOPS ON VENTILATORS.
BIOMARKERS WOULD BE TERRIFIC.
WE LOOKED AT THE PHOSPHOLIPID
CONTENT.
DR. ZIYADI TALKED ABOUT
YESTERDAY WITH PATIENTS FROM
CYSTIC FIBROSIS COULD WE
ESTABLISH BIOMARKERS FOR THESE
CONDITIONS.
ROBIN, I KNOW YOU HAVE WORKED IN
THAT SPACE A BIT WITH CHILDREN
WITH ILD SO MAYBE YOU WANT TO
COMMENT ON THAT.
>> I THINK THE BIOMARKER WORLD
DEVELOPMENT IS A TOUGH ONE.
PEOPLE HAVE BEEN DOING WORK FOR
A LONG TIME AND TRYING TO
VALIDATE A BIOMARKER.
I THINK DR. McCORMACK HAD SOME
EXCELLENT SUCCESS IN LAMB
THINKING ABOUT BIOMARKERS.
IT IS IMPORTANT WORK.
IT IS WORK THAT TAKES A LONG
TIME.
SO THAT IS WHY I LIKE TO THINK
ABOUT BIOMARKERS THAT CAN
GENERALIZE ACROSS MULTIPLE
DISEASES.
WE TAKE CARE OF KIDS WITH MANY
RARE DISEASES AND HOW DO WE
CREATE GENERALIZABLE APPROACHES
TO GET THE TREATMENT TO THE MORE
PATIENTS THE FASTEST?
WE HAVE PEOPLE ON THIS LINE WHO
CAN TALK ABOUT THAT.
>> JEN, TO YOUR POINT ON
BIOMARKERS, I'M SORRY, MY CAMERA
IS A LITTLE WEIRD, BUT, YEAH, WE
THINK DEVELOPING THOSE IS A GOOD
IDEA.
THERE IS DEFINITELY GOOD
EVIDENCE THE BLOOD BIOMARKERS
WILL BE USEFUL.
THE PLATFORM YOU USE IS
IMPORTANT.
THE NUMBER OF BIOMARKERS WILL BE
IMPORTANT.
FOR THE LUNG AND LUNG FUNCTION,
IT IS MORE COMPLEX THAN OTHER
SIMPLER PHYSIOLOGIC OUTCOMES.
I THINK YOU NEED MORE BIOMARKERS
THAN A HANDFUL.
WE ARE TRYING TO DEVELOP A PANEL
OF HUNDREDS OF BIOMARKERS IN THE
BLOOD WHICH IS COMPLEX BECAUSE
YOU HAVE TO VALIDATE IN SOMEONE.
LIKE ROBIN WAS MENTIONING WE
HAVE AN NIH GRANT AN RO1 ON
LOOKING AT HOW BIOMARKERS AND
IMAGING, HOW THEY BEHAVE
COMPARED WITH LUNG FUNCTION
MEASUREMENTS AND DEFINITELY PFTs
CAN BE STABLE OR UNCHANGED WHEN
YOU SEE DRASTIC DIFFERENCES IN
IMAGING WITH GAS TRAPPING, ZENON
IMAGING OR BIOMARKERINGS,
BIOMARKERINS WE HAVE EVIDENCE TY
ARE MORE SENSITIVE.
BIOMARKERS MAY COME EARLIER.
THEY NEED A LOT OF VALIDATION.
THEY ARE NOT EASY TO DEVELOP.
IT IS A COOL TOOL, BUT IT DOES
TAKE A LONG TIME.
IT WOULD BE GOOD IF THERE WERE
MORE FOLKS WORKING ON IT.
IT IS NOT AN AREA PEOPLE WANT TO
SPEND TIME ON.
>> THANK YOU FOR THAT.
WELL, WE ARE COMING UP TO THE
END OF OUR TIME HERE.
ANY FINAL COMMENTS FROM YOU
GUYS?
THANK YOU SO MUCH FOR GIVING
YOUR TIME AND SHARING YOUR
EXPERTISE.
THERE WILL BE MORE CONVERSATION
CERTAINLY THIS AFTERNOON.
HOPEFULLY YOU CAN JOIN BREAKOUT
SESSIONS AND HELP US THINK ABOUT
HOW WE BEST SUPPORT THIS.
>> THANK YOU ALL.
THIS WILL CLOSE OUT SESSION FOUR
AND RIGHT NOW ON OUR AGENDA WE
HAVE A LUNCH BREAK SCHEDULED
FROM 11:45 TO 12:15 P.M. EASTERN
TIME.
THEN WE WILL RETURN FOR OUR LAST
SCIENTIFIC SESSION, SUCCESS
STORIES FROM THE LUNG COMMUNITY.
I WILL BE CO-MODERATING THIS
SESSION WITH DR. AMY HAJARI
CASE, NEXT SLIDE, WHO IS THE
CHIEF MEDICAL OFFICER OF THE
PULMONARY FIBROSIS FOUNDATION
WHOSE MISSION IS TO SUPPORT
PULMONARY FIBROSIS RESEARCH,
EDUCATION AND ADVOCACY, SHE'S
ALSO A PRACTICING PHYSICIAN AND
SERVES AS THE DIRECTOR OF THE
ADVANCED LUNG DISEASE PROGRAM
AND MEDICAL DIRECTOR FOR
PULMONARY PIEDMONT HEALTHCARE,
AND THE DOCTOR WILL PROVIDE US
WITH INFORMATION FROM HER WORK
LATER.
NEXT SLIDE.
I WANT TO BRIEFLY INTRODUCE OUR
SPEAKERS BEFORE WE BEGIN THE
SESSION, AS A REMINDER, YOU CAN
POST YOUR QUESTIONS IN THE Q&A
TOOL AT ANY TIME DURING THIS
SESSION AND WE WILL BE
ADDRESSING THIS QUESTIONS DURING
THE PANEL DISCUSSION.
OUR FIRST SPEAKER WILL BE
MR. TRE LAROSA AND HE WILL GIVE
US A PERSPECTIVE ON CLINICAL
TRIALS ON PATIENT ENGAINLMENT AS
AN ADULT WITH CYSTIC FIBROSIS,
HE ALSO CURRENTLY SERVES ON THE
CF'S FOUNDATION CLINICAL
RESEARCH AND EXECUTIVE
COMMITTEE.
MR. LAROSA IS ALSO A PROJECT
MANAGER FOR THE NOGZAL
FOWBDATION FOR THE NATIONAL
INSTITUTES OF HEALTH WHERE WHERE
HE WORKS AS PATIENT AMBASSADOR
AND WORKS ON METABOLIC
DISORDERS.
OUR NEXT SPEAKER WILL BE MICHELE
MANNION, WHO IS THE EXECUTIVE
DIRECTOR OF THE PC D FOWBDATION
WHICH SHE FOUND INDEED 2002.
SINCE THEN SHE SERVED ON
NUMEROUS LEADERSHIP ROLE RELATED
TO POLICY DEVELOPMENT, ACCESS TO
CARE FOR INDIVIDUALS WITH LUNG
DISORDERS WITH A HEAVY EMPHASIS
ON THE PC D COMMUNITY AND SHE'S
COLLABORATED WITH INVESTIGATORS
WORLD WIDE AND HAS BEEN A FULL
PARTNER IN DEVELOPING AND
SUPPORTING A LARGE PRIMARY
RESEARCH NETWORK THAT IS IN
NORTH AMERICA AND EUROPE.
OUR NEXT SPEAKER WILL BE
DR. SHERYL NICKERSON NUTTER WHO
IS THE EXECUTIVE VICE PRESIDENT
OF RESEARCH AND DEVELOPMENT AT
THE 3 LAKES FOUNDATION, LEADING
THERAPIES, PULMONARY FIBROSIS
AND INTERSTITIAL LUNG DISEASES.
WITH OR PREVIOUS EXPERIENCE
SHE'S ADVANCED BOTH BIOLOGIC AND
SMALL MOLECULE DRUGS INTO
CLINICAL TRIALS FOR AUTOIMMUNE
AND INFLAMMATORY DISEASES AND
SHE CONTINUES TO FOCUS HER
EFFORTS ON DEVELOPMENT AND MODEL
SYSTEMS AND BIOMARKERS THAT CAN
CONTINUE TO SUPPORT CLINICAL
TRIAL OUTCOMES.
AND THEN OUR FINAL SPEAKER WILL
BE DR. FRANCIS Mc CORMACK, WHO
IS THE DIRECTOR DIVISION OF
PULMONARY CRITICAL CARE AND
SCHEEP MEDICINE AT THE
UNIVERSITY OF SIN SUDDEN ATY
COLLEGE OF MEDICINE, HE HAS A
FOCUSED ROLL ON PULMONARY
IMMUNITY, HIS INTERTITTIAL LUNG
DISEASES, INCLUDING LAMB, AND
PRINCIPAL INVESTIGATOR OF THE
MYLES TRIAL THAT LED TO THE FDA
APPROVAL OF [INDISCERNIBLE] AS A
SAFE AND EFFECTIVE TREATMENT
WITH LAM FOUNDATION, AND WITH
THAT I WOULD LIKE TO TURN IT
OVER TO OUR FIRST SPEAKER
MR. LAROSA.
>> THANK YOU MARRAH.
AND FIRST I WANT TO THANK THE
ORGANIZERS OF THIS WORKSHOP FOR
INVITING ME TO SPEAK AND PUTTING
TOGETHER A NICE AGENDA AND 1
THAT WORKS TO SOLVE THE
CHALLENGE OF ACTUALIZING
S TO PATIENTS.
I ALSO WANT TO DISCLOSE I HAVE
SERVED IN VARIOUS CAPACITIES FOR
THE CF FOUNDATION AND THAT MY
VIEWS ARE MINE AND DO NOT
REPRESENT MY EMPLOYER, THE FNIH,
MY TALK WILL WILL BE ABOUT AS AN
ADULT WITH CYSTIC PHOBEROSIS,
BUT ALSO AS AN PATIENT
ENGAGEMENT IN THE PATIENT SPACE.
CAN YOU PLEASE ADVANCE THE
SLIDE.
SO FIRST, A BIT ABOUT ME.
YOU CAN GO AHEAD AND ADVANCE THE
SLIDE 1 MORE TIME.
MY NAME IS TRE LAROSA AND I'M
KNOWA ADULT WITH
CYSTIC FIBROSIS, I AM 30 YEARS
OLD AND I'M A DELTA F508
HOMOZYGOTE, MEANING I'VE BEEN
ABLE TO BENEFIT FROM MODALATOR
THERAPY, TRIKAFTA, AND AS A KID
MY LIFE WAS FILLED WITH
APPOINTMENTS, CHEST THERAPY,
IVs, PILLS, POKES, PRODS,
SINUS INJURY, COUGH, EXPLAINING
TO OTHERS MY COULD YOU HAVE WAS
NOT CONTAGIOUS, INFECTIONS,
GOOGLE SEARCHES, PULMONARY
FUNCTION TESTS AND BLOWING SO
HARD I ENDED UP GETTING
HEADACHES AND USING GALLOW'S
[INDISCERNIBLE] THAT COMES WITH
HAVING A LIFE-SHORTENING ILLNESS
ISSUES MY EXPERIENCE WHILE IT
SHARES MANY HALLMARKS OF OF
OTHERS WITH CF IS BUT 1
EXPERIENCE.
IN MY FAMILY'S CASE, IT'S
GENERATIONAL, MY GRAND PARENTS
WERE FUNDRAISING IN THE 1960S
AND SEIVETS.
MY FATHER LOST HIS SISTER TO
CYSTIC FIBROSIS TO THIS HORRIFIC
DEC WHEN SHE WAS ONLY 12 YEARS
OLD AND HE WAS ONLY 18.
IT WAS 1968, TREATMENT LOOKEDDA
I LOT DIFFERENT THEN, THEY
HADN'T EVEN DISCOVERED THE CFTR
GENE OR IMPLEMENTED MUCH OF THE
STANDARD OF CARE WE NOW TAKE FOR
GRANTED.
YOU CAN GO AHEAD AND ADVANCE THE
SLIDE.
MY EXPERIENCE IS ALSO 1 OF A
SIBLING OF A LOVED 1 WITH CF.
IN 1988 MY PARENTS HAD MY SISTER
ELISSA RENE LAROSA, WHILE WE
BOTH CARRIED THE MOST COMMON
MUTATION OF CF OUR EXPERIENCES
TOED THE OPPOSITE ENDS OF
PROTOTYPICAL CF AND LOOKED FOR
DIFFERENT.
WE BOTH EXHIBITED VERY COMMON CF
PHENOTYPES BUT I MANAGED TO
MAINTAIN MY WEIGHT AND WHIEL I
CULTIVATED COMMON STRAINS OF CF
BACTERIA, I MANAGED TO BOUNCE
BACK FROM INFECTIONS QUITE
QUICKLY MOST OF THE TIME.
MY SISTER ON THE OTHER HAND
SPENT 30-40% OF HER LIFE ON
IVs OR IN THE HOSPITAL.
EVENTUALLY MY SISTER WOULD
CULTIVATE A [INDISCERNIBLE]
VECTOR WHICH TORPIED O'S HER
FIRST LUNG TRANSPLANT WHEN SHE
WAS ONLY 25 YEARS OLD.
SHE DEVELOPED BRONCH YIETIS
OBLIT RANS, AND NEEDED A
TRANSPLANT BY 2018, A FEW YEARS
LATER SHE WOULD DIE.
I FELT I COULD OVERCOME WHAT CF
WROTE FOR ME, ON THE OTHER HAND
CF SHAPED ME IN POSITIVE WAYS,
TOO, IN FACT, CF COME TO PROVIDE
ME A CAREER IN THE CF SPACE AND
NOW MORE BROADLY IN PATIENT AND
SCIENTIFIC PROJECT MANAGE.
CF ALSO PROVIDED ME AN INTIMATE
PERSPECTIVE INTO HUMAN BEHAVIOR.
FROM A YOUNG AGE I WAS DRAWN TO
SCIENCE FOR THE POWER TO EXPLAIN
THE UNKNOWN, SCIENCE IS A TOOL
WE CAN USE TO UNDERSTAND THE
WORLD AROUND US AND SCIENCE ALSO
HELPED US DRAMATICALLY IMPROVE
OUTCOMES IN THE CF COMMUNITY
COMPARED TO THE SHORT FATES OF
PEOPLE SUCH AS MY AUNT AND
SISTER.
YOU CAN ADVANCE THE SLIDES.
THOUGH I DREAMED OF BECOMES A
DOCTOR, MY CF WOULD CHANGE THOSE
NEEDS, I WOULD FORGO MEDICINE
AND WENT INTO SCIENCE.
I WOULD GO ON TO WORK IN JP
CLANCY'S CF LAB AT CINCINNATI
CHILDREN'S MEDICAL CENTER, WHICH
WAS THE SAME INSTITUTION THAT
PROVIDED BY CF CARE WHEN I WAS A
CHILD.
I ALSO MET DR. [INDISCERNIBLE] 1
OF THE OTHER SESSION SPEAKERS
AND DR. [INDISCERNIBLE] 1 OF MY
CO-PANELISTS WHO TOOK CARE OF MY
SISTER AT THE UNIVERSITY OF SIN
SEN ILLEGALSEN ATY.
AT THIS POINT IN MY LIFE I WOULD
SPEAK TO I LOT OF CF DOCTORS,
RESEARCHERS AND OTHER PATIENTS,
ALL INVOLVED WITH CF RESEARCH
AND MEDICINE IN DIFFERENT
CAPACITIES, PEOPLE WHO WERE
WRITING PROTOCOLS, SHIFT IN
INCORPORATING PATIENTS TRIAL,
THE DEVELOPMENT PROCESS,
PATIENTS PRACTICES RUNNING
ACROSS THE GAMUT OF PEOPLE
ELIGIBLE FOR MODULATORS FOCUSED
ON FOLK WHO IS LIVED IN
DIFFERENT COUNTRIES AND DIDN'T
EACH HAVE ACCESS TO STANDARD OF
CARE SUCH AS HYPERTONIC SALINE.
I CAME TO REALIZE WE WERE ALL
TALKING ABOUT THE SAME DETAILS
IN VERY DIFFERENT LANGUAGE ANDS
THEREFORE OFTEN TALKING PAST 1
ANOTHER WHICH INPIERED ME TO
START WRITING ABOUT MY LIVED
EXPERIENCE AND THE SCIENCE
UNDERLYING CF AND BRIDGE THOSE
GAPS.
THIS ALSO LED ME TO PATIENT
ADVOCABULARY KASP A R EXPE
PARTICIPATE NOTHING CLINICAL
TRIALS.
YOU CAN GO AHEAD AND ADVANCE THE
SLIDE, PLEASE.
THE FIRST MAJOR CLINICAL TRIAL I
ENROLLED IN WAS CALLED THE
IGNITE STUDY WHICH SOUGHT TO
INVESTIGATE THE USE OF GALLIUM
NITRATE FOR PSEUDOMOANUS AND CF.
I WAS FASCINATED BY THIS SINCE I
WAS WORKING IN A CF LAB, PRIVATE
SECTOR LODGED ENOUGH TO TAKE
TIME OFF WORK AND PRIVILEGED
ENOUGH TO TAKE TIME OFF WORK AND
LAY IN A HOSPITAL BED AND GET
PAID TO WATCH SONS OFAN ARCHY
FOR A WEEK AND WHILE I COULD
HAVE RECEIVED PLACEBO, I WAS
EAGER TO SEE WHAT THE STUDY
WOULD DO FOR MY LUNGS.
AFTER 5 DAYS MY LUNG FUNCTION
WENT UP 7%, I RISE I HAD ONLY
SEEN FROM THE USE OF ANTIBIOTICS
OR MONTHS OF PHYSICAL TRAINING,
I THOUGHT THIS BODE WELL FOR THE
POSSIBILITY OF STUDY MEETING THE
PRIMARY INFLUENCE AND I
EVENTUALLY I LEARNED I DID
RECEIVE DRUG, BUT THE STUDY DID
NOT REACH PRIMARY END POINTS AND
I WAS DISAPPOINTED.
I LEARNED A LOT ABOUT THE
NUANCES OF STUDY DESIGN, PRIMARY
POINTS AND HOW IMPORTANT IT WAS
FORFONTS TO BE INVOLVED IN
STUDY DESIGN AND HOW IMPORTANT
IT WAS TO REDUCE BARRIERS TO
PARTICIPATE NOTHING ADVANCED
CLINICAL TRIALS.
PLEASE ADVANCE THE SLIDE.
I EVENTUALLY JOINED A SMALL
COMPANY WHERE I WORKED IN
PATIENT REPORTED OUTCOMES ACROSS
MANY DISEASES, I ALSO SERVED ON
MANY COMMITTEES INCLUDING CF
ADULT ADVISORY COUNCIL, PROTOCOL
REVIEW COMMITTEE AND
PATIENT-FACING AND
SCIENCE-FACING CONFERENCES.
THESE EXPERIENCES WOULD SHAPE
THE NEXT MAJOR MILESTONE OF MY
LIFE.
JOINING THE CF THERAPEUTIC
NETWORK DEVELOPMENT CLINICAL
EXECUTIVE RESEARCH EXECUTIVE
COMMITTEE KNOWN AS THE CREC, IT
GOVERNS AND SANCTIONS STUDIES IN
THE TDM, THIS ROLE WAS 1 OF THE
MOST MEANINGFUL IN MY LIFE AS IT
WAS YEARS AND YEARS OF
CULMINATION IN THE SCIENTIFIC
SPACE.
ON THIS COMMITTEE WE ANALYZE THE
SPECIFIC TRIALS TO THE TDN WHILE
INSURING WE ARE THE BEST
POSSIBLE CUSTODIAN FOR THE
COMMITTEE, WE HAVE TO MINDFUL OF
THE NUANCES IN THE CF RESEARCH
AND INCLUDING SAIRCHGZING
STUDIES THAT DON'T SUCCEED
EITHER FOR RECRUIT, SAFETY OR
EFFICACY REASONS.
I TALK A LOT ABOUT THE
IMPORTANCE OF HOPE BUT ALSO THE
PERSON OF SUCCESS, IN MY VIEW,
PATIENT ENGAGEMENT IN CLINICAL
RESEARCH IS NOT A EMILY THED
RESEARCH BUT A FORM OF CAPITAL
THAT BEGETS ADDITIONAL CAPITAL.
IN OTHER WORDS PATIENTS THAT
ENROLL IN CLINICAL TRIALS THAT
SUCCEED OR LEARN IN THE PROCESS
ITSELF SUCH AS WHEN I ENROLL
IN THE IGNITE STUDY.
YOU CAN ADVANCE THE SLIDE.
CAN YOU ADVANCE THE SLIDE?
I THINK THERE SHOULD BE 1 MORE
SLIDE?
MAYBE NOT.
BUT GO AHEAD AND YOU CAN GO BACK
1.
TO CONCLUDE MY TALK, I WANT TO
BRIEFLY TALK ABOUT MY ROLE AT
THE FOUNDATION FOR THE NATIONAL
INSTITUTES OF HELT WHICH IS A
NONPROFIT THAT SEEKS TO ADVANCE
THE MISSION OF THE NIH.
HE
THIS ROLE, WE FACILITATE
PUBLIC PRIVATE PPUIPS
BETWEEN THE NIH BEING ACADEMIA
AND INDUSTRY ORGANIZATIONS.
I WEAR 2 HATS HERE, I AM A
SCIENTIFIC PROJECT MANAGER FOR A
BIOMARKERS CONSORTIUM PROJECT
SEEKING TO VALENTINED DIADIC A
PROGNOSTIC BIOMARKER IN
METABOLIC DYSFUNCTION
[INDISCERNIBLE] HEPATITIS AND I
ALSO HELP TO MANAGE PATIENT
ENGAGEMENTTS.
THE FNIHTHS A SPECIAL AREA WHERE
WE GET TO STUDY THINGSA THE A
DIFFERENT DISEASE PROCESS, EVERY
AREA IS MATURITY IN TERMS OF
PATIENT ENGAGEMENT BUT IT'S
CRUCIAL WHEN CHECKING BOXES FOR
PEOPLE WITH LIVED EXPERIENCE.
IT'S NECESSARY TO HELP OPTIMIZE
DRUG DEVELOPMENT IN THE
ADVANCEMENT OF THE FIELD FROM
THE VERY ONSET OF AN IDEA.
I INVITE THE VOAKS IN THE ROOM
HERE TODAY TO CHALLENGE
THEMSELVES TO IMAGINE WHAT IT
MUST BE LIKE TO BE A PATIENT
BECAUSE WHILE PATIENTS SHOULD BE
IN EVERY ROOM, WE AREN'T ALWAYS
AND THAT'S WHEN IT'S
PARTICULARLY NECESSARY FOR THE
DOCTORS AND RESEARCHERS TO
EXERCISE THAT MUSCLE.
I LOOK FORWARD TOA TALKING WITH
YOU MORE AND HAPPY TO MEET TO
DISCUSS ANYTHING IN GREATER
DETAIL AND THANK YOU AND I'M
EXCITED TO PARTICIPATE IN THE
PANEL LATER.
>> THANK YOU TRE.
THAT WAS VERY INSPIRING.
IN THE PANEL DISCUSSION AND LOOK
FORWARD TO IT, SO OUR NEXT
SPEAKER, IS MICHELLE MANNION AND
SO, I WOULD LIKE I TURN IE L OVR
TO HER.
>> HELLO.
MY NAME IS MICHELE MANNION, AND
I'M THE EXPECT RETURN OF RESULTS
DIRECTOR AT PRIMARY CELLULAR
DISKINNIESIA, IT WAS GREAT TO
FOLLOW A MEMBER OF THE CF
FOUNDATION BECAUSE I THINK WHEN
WE ARE LOOKING AT SUCCESS IN
THERAPEUTIC DEVELOPMENT FOR A
RARE DISEASE, THERE IS NO BETTER
GOLD STANDARD THAN THE
CYSTIC FIBROSIS FOUNDATION.
I WANT TO MENTION THAT WHILE I'M
HERE TO TALK ABOUT PC D AND THE
EXPERIENCE OF THE PC D
FOUNDATION, AFTER DOING THIS FOR
30 YEARS AND HAVING VALUED
COLLEAGUES ACROSS THE RARE DEC
SPACE IT HAS BECOME OBVIOUS TO
ME THAT WHILE WE HAVE A
DIFFERENT DISEASES WE'RE
WORKING, BUT A LOT OF THESE
ADVOCACY GROUPS ARE THE SAME.
SO CONSIDER OUR EXPERIENCE AS
REPRESENTATIVE OF THE RARE
DISEASE EXPERIENCE ESPECIALLY
FOR LUNG DISEASE.
NEXT SLIDE.
SO WHAT IS PC D?IS
LIKE CYSTIC FIBROSIS, PRIMARY
SILLIARY DISKINNIESIA, IT'S THE
DISORDERS OF CLEARANCE, THIS
ENCLUEDERS SEPARATIVE OF
AIR WAY DISORDERS, SO ANY AIR
WAY INFECTIOUS KIND OF DISEASE
WOULD BE CATEGORIZED IN THIS
AREA AND WE'RE TALKING HERE
ABOUT GENETIC DISORDERS.
THE ESTISS THAT THERE ARE
ABOUT 1 IN 7500 TO 1 IN 15,000
PEOPLE WITH PC D, IT AFFECTS ALL
GENDERS,LLS, ETHNICITIES, RACESD
DESPITE THE FACT THAT ORGAN
PLACEMENT ABNORMALITIES, THESE
EFFECTS OCCUR IN 50% OF THE
POPULATION, DIAGNOSIS AND STILL
OFTEN DELAYED BY YEARS OR EVEN
DECADES, THERE ARE CURRENTLY NO
APPROVED THERAPIES FOR PC D.
SO THE COMMON SYMPTOMS OF PC D,
I MENTIONED THE LATERALITY
DEFECTS BUT RIGHT AWAY, THE
SYMPTOMS ARE EVIDENT AT BIRTH.
MOST OF THE PATIENT POPULATION,
MORE THAN 80% WILL HAVE NEONATAL
RESPIRATTRESS DESPITE
BIRTH ANDEN THIS MOSTLY,
THAT IS A SURVIVABLE CONDITION
ALTHOUGH SOME BABIES DO NOT
SURVIVE THAT NEONATAL PERIOD BUT
AS THEY GROW, FIRST YEAR OF
LIFE, WE START WITH CHRONIC
UPPER AND LOWER AIR WAY
INFECTIONS.
HEARING LOSS IS VERY COMMON IN
CHILDREN, BOTHIVE AND
NEUROGENIC, AS PATIENTS PROGRESS
THEY GET INCREASINGLY BAD BUGS
AND AIR WAY INFECTIONS LEADING
TO DAMAGE TO THE AIR WAYS CALL
BRONCHIECTASIS AND THIS LEADS
THEM TO TRANSPLANT OR EARLY
RESPIRATORY FAILURE.
ADDITIONALLY, SILLIARY ARE
IMPORTANT FOR ORGANS OF
PRODUCTION, SO INFERTILITY ARE
SEEN IN THESE PATIENTS.
LESS COMMONLY PC D CAN BE
ASSOCIATE WIDE SYNDROMIC FORMS
OR X-LINKED FORMS AND YOU WILL
SEE THINGS LIKE RETINAL
LOCATIONINNITEIS PIGMENTOSA, AND
BRAIN MALFORMATIONS, AND
OCCASIONALLY DEFEBTS THAT ARE
ASSOCIATE WIDE LATERALITY ISSUES
CAN BE QUITE SEVERE INCLUEDINGRT
DEFECS, CHILDREN WITH PC D WITH
SITUS AMBIGUOUS IS WHAT WE CALL
THIS CATEGORY.
OF HAVING CONGENITAL HEARTRISK
DEFECTS AND WELL IS A
INCREASE IN SKELETAL ANOMALIES
INCLUDING SCOLIOSIS AND
[INDISCERNIBLE] IN THIS PATIENT
GROUP.
NEXT SLIDE.
SO WHAT ARE CILIA?
WHAT WE'RE TALKING ABOUT WITH PC
D ARE MODAL CILIA, THERE ARE
SINGLE PRIMARY/SENSORY
SILLIARYIA, IN EVERYIAELL OF THE
BODY E RED BLOOD CELLS BUT
THEY'RE NOT WHAEY TALKING
ABOUT WITH PC D, IT IS ONLY THE
CATEGORY OF MODAL CILIA, AND YOU
CAN SEE HERE THAT THEY KIND OF
GROUP TOGETHER IN THE CILIATED
EPITHELIUM AND THE ROLE IS TO
MOVE BACK AND FORTH IN A
SWEEPING FASHION TO GET MUCUS
THE AIROHIS IS ADEBRIS OUT O
CRITICAL PART OF HOST, PULMONARY
HOST DEFENSE AND IN DISORDERS
UPON OF GENETIC, IT IS
EFFECTIVE.
IN THE CF IS THE MUCUS THAT IS
THE PRIMARY PROBLEM, IN PC D IT
IS THE CILIA.
NEXT SLIDE.
SO WHEN YOU SEE PICTURES OF
CILIA, THEY LOOK PRETTY SIMPLE,
THEY LOOK LIKE LITTLE HAIR OR
WHIP LIKE STRUCTURES BUT THEY
ACTUALLY ARE VERY COMPLEX.
SO THIS IS A GRAPHIC OF A MODAL
CILIUM AND YOU CAN SEE THAT IT'S
ANCHORED TO A BASE AND THIS IS
WHAT IS ON THE EPITHELIAL
THAT ENTIRE STRUCTURE
WITH THE SILLIARY AXINE ANDIL TE
BASE IS OVER 500 PROTEINS, 5 SOF
WE LOOK JUST AT THE PART THAT IS
INVOLVED IN PC D, AXONINE
AND DO A CROSS SECTION, CAN YOU
SEE ALL THESE DIFFERENT
STRUCTURAL ELEMENTS.
ALL OF THEM HAVE A PROTEIN
INVOLVE WIDE THEM AND THE
ESTIMATE IS THAT THERE ARE ABOUT
200 SEPARATE PROTEINS INVOLVED
IN THESE -- CREATING THESE ARMS
ORSEHEXONINES.
NEXT SLIDE.
SO WHEN CILIA DON'T WORK THERE
ARE MULTIPLE CLINICAL
CONSEQUENCES.
WE'VE TALKED A LITTLE BIT ABOUT
THE ORGAN PLACEMENT AND
LATERALITY DEFECTS AND THE
ASSOCIATION WITH CONGENITAL
HEART DEFECTS, THERE ARE ALSO
FOUND IN THE APPEND MALCELLS OF
THE BRAIN, THE CELLS OF THE
BRAIN SO SOMETIMES YOU WILL SEE
HYDROCEPHALUS IN PC D, EAR
INFECTED BY THE PC D, UPPER AND
LOWER RESPIRATORY TRACT ARE
PROBABLY THE PRIMARY AREA OF
MORBIDITY IN PC D, BUT THERE ARE
ALSO ISSUES WITH REPRODUCTION
BECAUSE OF CILIA IN THE OVERDUCT
AND BECAUSE SPERM FLAGELLA HAVE
THE SAME MOTOR PROTEINS THAT
AIRWAY CILIA HAVE.
SO THE GRAPHIC TO THE RIGHT,
JUST SHOWS THE KIND OF 4 BUCKETS
OF LATERALITY THAT WE SEE IN PC
D, SITUS, SOLITUS, THAT'S THE
TYPICAL, AND THE SITUS,
INVERSUS, TOTALIS, WHICH IS
REVERSED, AND THEN SITUS,
AMBIGUOUS OR HETEROGENEOUS ORY
TAXI WHICH CAN HAVE
DEVELOPMENTAL
ENDOCRINOLOGYINATING EFFECTS.
NEXT SLIDE.
SO I GOT INTO THIS FOR THE SAME
REASON MOST PEOPLERE DO TO
ADVOCATE FOR THIS DISEASE, AT
THE TIME WHEN SHE WAS DIAGNOSED
IN 2001 WAS WHERE CAN WE TAKE
HER TO GET RESEARCH AND ANSWERS,
I WAS TOLD THERE WOULD NEVER BE
RESEARCH ON THIS DISEASE, IT WAS
TOO RARE AND NOT APPEALINGDO
RESEARCH.
AT THIS TIME THERE WAS
, SO I WHAT LITTLE
RESEARCH ITLOULDSE AT THE LIBRAY
TRYING TO FIND ANY SORT OF AOR
ORGANIZATION FOR THIS DISORDER
AND THERE WAS NOTHING.
SO AS THE EARLY INTERNET CAME
ONLINE, I CHECKED EVERY NOW AND
THEN AND FINALLY IN 1991 FOUND
THERE WAS RESEARCH GOING ON AT
THE UNIVERSITY OF NORTH CAROLINA
CHAPEL HILL.
AND TOOK MY DAUGHTER DOWN THEREW
T THAT WAS T REALLY THEEA TS
OF THINKING MAYBE WE COULD DO
SOMETHING HERE.
AND WE HAD BECAUSE OF THE CLOSE
ASSOCIATION WITH
CYSTIC FIBROSIS, WE HAD A LOT OF
SIMILAR DOCTORS.
WE ARE SHARING PHYSICIANS, WE
HAD A LOT OF SIMILAR TREATMENT
NEEDS AND SO IT MADE SENSE TO
FOLLOW WHAT THE CF FOUNDATION
HAD DONE FOR PC D ONLY DOING IT
WITH MUCH, MUCED BUDGET.
BUT OUR MISSION FROM THE
BEGINNING WAS TO BE GOOD
PARTNERS TO MAKE SURE RESEARCH
COULD HAPPEN BECAUSE OUR FEELING
WAS THE BEST WAY TO SUPPORT
PATIENTS IS TO MAKE SURE THEY
HAVE ACCESS TO THE BEST CARE IS
THE THERAPIES THEY NEED.
SO WE ESTABLISHED OURSELVES AS A
NONPROFIT ORGANIZATION IN 2001
AND BECAME TAX EXEMPT, AND THEN
SERENDIPITOUSLY IN 2002, THE
RARE DECS CLINICAL RESEARCH
NETWORK WAS FORMED AND WE BECAME
1 OF THE FIRST RESEARCH
CONSORTIA THROUGH THAT PROGRAM
WITH THE GENETIC DISEASE,
DISORDERS AND MUCUS SILLARY
CONSORTIUM AND THAT START INDEED
2002.
ONE THING I WANT TO MENTION
BECAUSE IT'S RELEVANT FOR A LOT
OF PATIENT GROUPS IS THAT WE ARE
ASKED TO DO A LOT AS PATIENT
GROUPS AND MOST GROUPS, THIS
IS A VOLUNTEER EFFORT AND WE'VE
BEEN TALKING ABOUTEN THIS A LOT
INTERNATIONALLY WITH SOME OF THE
PATIENT ADVOCACY GROUPS FOR PC D
AND OTHER PARTS OF THE WORLD.
THINGS REALLY CHANGE FOR US, AND
MOVED MUCH MORE QUICKLY WHEN I
WAS ABLE TO DO THIS ASS A
WHEN WE HAD THE RESOURCES TO
REALLY INVEST IN THE
ORGANIZATION, AND SEVERAL YEARS
AGO I WAS CALLED BY SOMEBODY
FROM NCATS WHO ASKED ME IF I HAD
A SENSE FOR HOW MANY RARE DEC
ORGA HADGA A
REVENUE OFON OR MORE AND
WHEN I GOT DONE LAUGHING, I SAID
POSSIBLE LE 2-3% BUT THAT WOULD
BE ABOUT IT.
THE CF FOUNDATION IS A UNICORN
IN THIS SPACE, MOST OF US ARE
OPERATING ON VERY, VERY LIMITED
RESOURCES L WE THINK THAT'S
IMPORTANT TO MAKE CLEAR TO
POTENTIALNT PARTNERS.
NEXT SLIDE.
SO WHEN THE GDMCC WAS FORMED
THIS WAS AN ITHE
OPPORTUNITY FOR US TO GET
FOUNDATIONAL RESEARCH DONE IN PC
D THAT WE WOULD NOT HAVE HAD THE
ABILITY TO PAY FOR PROBABLY TO
THIS DAY, SO I THINK LOOKING FOR
OPPORTUNITIES LIKE THIS, WHERE
YOU CAN HAVE COLLABORATIVE
RESEARCH CONSORTIA, ORRE CAN
LOOK FOR OPPORTUNITIES
THROUGH PRIVATE VENTURES, IT'S
REALLY IMPORTANT TO GET THAT
KIND OF BOOST TO MOVE THINGS
ALONG AND WHAT HAPPENED THROUGH
THE GDMCC IS THAT WE STARTED
SMALL WITH 5 SITES AND THEN WE
GREW OVER TIME AND WHAT BECAME
CLEAR AT LEAST TO ME AS AN
OBSERVER AND PARTNER IN THIS
PROGRAM, IS THAT YEAH, THERE IS
INTEREST AND IF WE BUILD A
NETWORK, WE WILL FIND PATIENTS.
NEXT SLIDE.
ANDNE SO FROM THAT, THE PC D
FOUNDATION, PATH TO CLINICAL
TRIALS WAS ESTABLISHED AND THIS
REALLY WAS AN EFFORT ON OUR OPAC
HERE FROM THE CF FOUNDATION, WE
CALLED HIM AND SAID BOB WE WANT
TO DO WHAT YOU GUYS DID, WE WANT
A CENTERS NETWORK AND WE WANT A
REGISTRY AND OH BY THE WAY WE
HAVE ABOUT $2500.
AND TO HIS CREDIT HE DIDN'T
LAUGH OR HANG UP ON ME.
BUT HE SAID, YOU KNOW WHAT I
WOULD DO IS PUT THIS PACKAGE IT
INTO SOMETHING CALLED THE PATH
TO CLINICAL TRIALS AND TRY TO
RAISE MONEY.
SO THAT IS EXACTLY WHAT WE DID
AS AN OUTGROWTH OF THE GDMCC.
THE PC D FOUNDATION CREATED A
CENTERS NETWORK AND LAUNCHED A
REGISTRY.
NEXT SLIDE.
AND SO HERE ARE SITES TODAY, WE
HAVE 63 SITES INCLUDING THE 8
GDMCC SITES, THESE SITES ARE ALL
ACCREDITED AND HAVE AGREED TO DO
-- FOLLOW THE GUIDELINES FOR
DIAGNOSIS AND TO PARTICIPATE IN
OUR RESEARCH REGISTRY AND ALSO
TO PARTICIPATE IN RESEARCH
OPPORTUNITIES AS THEY COME UP.
NEXT SLIDE.
AND SO OUR REGISTRY STARTED
ABOUT 4 YEARS AGO, STILL PRETTY
SMALL, BUT WE ARE BEING VERY
CAUTIOUS ABOUT WHO WE PUT IN THE
REGISTRY BECAUSE WE HAVE A BIG
PROBLEM, NOT JUST WITH MISSED
DIAGNOSIS, IN PC D BUT WITH
MISDIAGNOSIS, SO ALL OF THE
PATIENTS IN OUR REGISTRY, WE
WANT THEM TO BE RESEARCH READY,
MEANING THE DIAGNOSIS HAS TO BE
CONFIRMED GENETICALLY, OR BY
HALLMARK THE STRUCTURAL
DEFECS THAT ARE KNOWN TO CAUSE
PC D.
I WOULD LIKE TO POINT OUT HERE
THAT WE'RE TRYING VERY HARD TO
GROW OUR ADULT SIDE OF THIS AND
PATIENTS IN OUR REGISTRY RIGHT
NOW HAVE CONFIRMED PC D VIA
GENETICS.
NEXT SLIDE.
WE ALSO ARE TRYING TO FOLLOW
CF FOUNDATION'S MODEL IN HAVING
A DRUG DEVELOPMENT PIPELINE.
SO THIS IS A LITTLE BIT
AMBITIOUS, BECAUSE THERE ARE NOT
REALLY MANY DRUGS DEVELOPED --
IN DEVELOPMENT FOR PC D, AND
NONE APPROVED FOR PC D.CT IF THN
DEVELOPMENT, IF THERE ARE DRUGS
WE THINK WOULD BE APPROPRIATE
FOR OUR POPULATION, WE PUT THEM
ON THIS PIPELINE BECAUSE WE B WT
TS TO KNOW THAT THERE'S
HELP COMING ANDOMHAT WE WERE
WORKING THIS.
NEXTLIDE.
SO WE'VE DONE A COUPLE CLINICAL
TRIALS IN PC D AND I WANT TO
SHARE THE LEARNINGS WE'VE HAD
BECAUSE I THINK -- WE'RE VERY
EXCITED PARTICIPATE IN TRIALS,
IT WAS REALLY EXCITING TO HAVE
SOMEONE INTERESTED, WE KNEW
THERE WOULD BE SOME CHALLENGES
BUT SOME CHALLENGES WE DIDN'T
ANTICIPATE AND JUST WANT TO KIND
OF BRING THOSE TO PEOPLE'S
ATTENTION.
SO WE KNEW THERE WOULD BE ISSUES
WITH RECRUITMENT, IT'S A RARE
DISEASE, IF YOU LOOK AT THESE
GENE THESE ARE 56 ULTRA RARE
DISEASES.
SO WE ANTICIPATED THAT, WE ALSO
KNEW THERE WOULD BE ISSUES WITH
CONFIRMING THE DIAGNOSIS TO GET
PEOPLE INTO WITH GENETIC TESTINA
PROBLEM, SO WE NEED MORE TESTING
AND TO REALLY GOOD
INTERPRETATION OF TEST RESULTS
FOR RARE DISEASES.
WE KNEWHERE WAS GCAL
DISEASES THAT WOULD BE A PROBLEM
FOR PARTICIPATION AND WE WERE
ALSO AWARE OF THE RESEARCH NAIVE
COMMUNITY THAT REALLY DIDN'T
HAVE MUCH EXPERIENCE WITH THIS
AND DIDN'T NECESSARILY
UNDERSTAND THE IMPORTANCE.
AND WE KNEW THAT IDEBTIFICATION
AND THE PATIENT CENSUS PER SITE
COULD BE CHALLENGING WITH
RECRUITMENT.
WHAT WE DID NOT ANTICIPATE
THAT WE W GET ACTIVE
RESISTANCE TO CLIRIALSLI BY
SOME OF OUR SISTER GROUPS IN
ARBITRATE COUNTRIES AND THAT CAN
BE DAMAGING GLOBALLY.
SO THAT WAS A SURPRISE AND AN
UNPLEASANT SURPRISE.
AND THEN WE HAD SITE PERFORMANCE
ISSUES THAT WE HADN'T
ANTICIPATED AND 1 OF THE BIG 1S
IN THIS CAME UP EARLIER IN THE
MEETING TODAY IS CONTRACTING
DELAYS AND I WILL TELL YOU THAT
AS WE LOOK AT MOVING INTO OTHER
TRIALS, WE ARE VERY WELL AWARE
OF WHICH ACADEMIC CENTERS TOOK 2
YEARS TO GET PAPERWORK DONE, AND
THEY ARE NOT REAL,A PEELING WHEN
WE'RE LOOKING TO PARTNER WITH
SITES FOR RESEARCH, CLINICAL
RESEARCH.
WE HAD A LOT OF TROUBLE WITH THE
LACK OF COORDINATOR AVAILABILITY
AND THIS MADE IT VERY SLOW TO
GET PATIENTS ENROLLED.
NEXT SLIDE.
SO SPECIFIC STUDY CHALLENGES, WE
DID A STUDY ABOUT 7 YEARS AGO
WITH AN ENAC INHIBITOR, THE
COMPANY WAS CALLED PARRION AND
THE STUDY WAS THE CLEAN PC D
STUDY, THIS WAS AN INHALED ENAC
INHIBITOR, THE IT T WAS TO PROVE
AIRWAY CLEARANCE ISSUES THERE
WERE 2 POSITIVE RESULTS
PUBLISHED IN LANCET STUDY, THIS
IS AN OLD STU IT JUST CAME
OUT THIS YEAR AND THAT'S BECAUSE
THE COMPANY THAT LICENSED THE
DRUG PARRION HELD ON TO THE DATA
AND WE COULD NOT GET IT
PUBLISHED.
SO RIGHT NOW THERE'S PHASE 3
PLANS BUT FUNDER NEEDS TO BE
FOUND TO COMPLETE THIS TRIAL.
IT REQUIRED MORE THAN 30 SITES
AND 8 COUNTRIES TO COMPLETE
ENROLLMENT OF THE PATIENTS,
AGAIN THIS WAS 7 YEARS AGO SO WE
MAY NOT BE FACING THE SAME
CHALLENGES.
SOME SITES DID NOT EVEN GET
THE-HAD FINISH THEIR CONTRACTING
STUFF THROUGH THEIR ACADEMIC
SITES UNTIL AFTER THE STUDY
CLOSED SO THEY NEVER EVEN GOT A
PATIENT IN, AND FOR AN INDUSTRY
PARTNER, THERE'S A OHE MONEY
THAT GOES INTO BRINGS SITES ON
BOARD SO SITE SELECTION IS
CRUCIAL.
THE STUDY DESIGN WAS
CHALLENGING, WE WERE INVOLVED IN
HELPING WITH THE STUDY DESIGN
BUT THE THINGS THAT WE FELT
WOULD MAKE IT DIFFICULT FOR
PATIENTS TO PARTICIPATE WERE
OVERRULED BY THE NEEDS OF THE
REGULATOR AND THAT ALSO CREATED
SOME CHALLENGES.
SO WE LEARNED CAREFUL SITE
SELECTION IS CRUCIAL AND THAT
ALL FUTURE PC D CLINICAL TRIALS
ARE GOING TO REQUIRE
INTERNATIONAL COLLABORATION
BECAUSE THERE JUST AREN'T ENOUGH
PATIENTS IN ANY 1 REGION.
NEXT SLIDE.
SO WE'RE CURRENTLY INVOLVED WITH
PHASE 1 B STUDIES THIS IS THE
NOVEL INHALED MRNA THERAPY AND
IT'S DESIGNED TO REPAIR THE
UNDERLYING DEFECT OR AT LEAST
REPAIR THE MESSAGING FOR THE
UNDERLYING DEFECT IN PC D THAT'S
CAUSED IN VARIANTS IN DNAI1.
THERE ARE SITES IN THE UK,
GERMANY AND DENMARK IN ADDITION
TO US, AND BECAUSE OF THE
DIAGNOSTIC ISSUES AND THE
SPECIFICALLY FOR DNAI1, THE SITE
IS STUDYING TESTING FOR ADULTS
WITH PC D, UPTAKE ON THIS AS
BEEN SLOWER THAN ANTICIPATED AND
PART OF THIS IS BECAUSE THE
CLINICIANS THAT ARE INVOLVED ARE
A LITTLE AMBIVALENT ABOUT IT,
IT'S BEEN CHALLENGING TO FIND
9-10 PATIENTS WHO FIT THE
INCLUSION CRITERIA AND ARE ABLE
TO TRAVEL AND SPEND A WEEK ATLAS
VEGAS AT THE CRO.
THERE IS SIGNIFICANT INTEREST IN
PARTICIPATING EXPRESSED BY
PATIENTS BUT WE HAVE DONE
SURVEYS MANY TIMES TO FIND OUT
WHAT KIND OF BARRIERS THERE ARE
TO PARTICIPATION AND PATIENTS
ALWAYS ARE FAR MORE WILLING TO
PARTICIPATE IN GENERAL THAN WHEN
THE SPECIFIC REQUIREMENTS OF THE
STUDY COMES OUT.
I DO ALSO WANT TO MAKE A POINT
HERE THAT SOMETIMES WE HEAR THAT
THEY DON'T WANT TO BE
INCONVENIENCED, I DON'T THINK
THAT'S TRUE.
IT'S NOT A CONVENIENCE ISSUE,
IT'S THAT THEY'RE LITERALLY
JEOPARDIZING THEIR EDUCATION,
JOBS SO THERE'S A LOT OF THINGS
PATIENTS HAVE TO THINK ABOUT
BEFORE THEY COMMIT TO A CLINICAL
TRIAL AND THE MODEL CITIZENNER
WE DID DO TO MAKE CLINICAL TRIAL
STUDY DESIGN ACCOMMODATE THESE
THINGS, THE BETTER IT'LL BE TO
RECRUIT INTO TRIALS.
SO AGAIN WE LEARN THAT SITE
SELECTION IS CRUCIAL.
YOU HAVE TO HAVE THE RIGHT SITES
THAT ARE MOTIVATED AND WILL FIND
THE PATIENTS AND THAT AGAIN,
WE'RE GOING TO NEED
INTERNATIONAL COLLABORATION.
NEXT SLIDE.
ONE OF THE THINGS WE DID TO HELP
OVERCOME THESE CHALLENGES, WE
DID A SERIES OF WEBINARS WITH
RICO TO TALK ABOUT GENETICS,
GENETIC BASE THERAPIES AND ABOUT
THE THERAPY THAT RECODE HAD ON
OFFER, THESE WERE WELL ATTENDED.
WE HAD CLOSE TO 200 PEOPLE AT
EACH OF THESE WEBINARS AND WE
DID PICK UP SOME PATIENTS FOR
RECRUITMENT THROUGH DOING THIS
JOINT EDUCATIONAL ACTIVITY.
NEXT SLIDE.
WE ALSO HELD OUR FIRST EVER
GLOBAL PATIENT ADVOCACY SUMMIT
IN LONDON IN 2024 TO GET
EVERYBODY ALIGNED ON MESSAGING
ABOUT THE IMPORTANCE OF CLINICAL
TRIALS.
IT WAS VERY INTERESTING, I THINK
IT WAS SHOCKING TO ME, HOW
POORLY RESOURCED SOME OF THESE
GROUPS ARE, HOW WILLING AND
DEDICATED AND COMMITTED THEY ARE
BUT THEY REALLY HAVE VERY LITTLE
TO WORK WITH.
NEXT SLIDE.
SO OUR NEXT PLAN TO OVERCOME
CHALLENGES IS AGAIN, TO BORROW
FROM THE CYSTIC FIBROSIS
FOUNDATION.
THEY HAVE HAD TREMENDOUS SUCCESS
WITH THEIR THERAPEUTICS
DEVELOPMENT NETWORK, WE ARE
TRYING TO LAUNCH WHAT WE CALL
THE CLINICAL NETWORK FOR TRIALS,
WHICH WILL BE A VERY MINISCALED
DOWN VERSION OF THAT, BUT WE'RE
ATTEMPTING TO CREATE A 1 STOP
SHOP FOR INDUSTRY PARTNERS AND
DEVELOPERS AND VENTURE C
APITALISTS SO THAT THERE'S 1
POINT OF CONTACT AND FROM THAT
THEY WILL GET INTO OUR NETWORK.
THIS IS KIND OF OUR
SUSTAINABILITY PLAN FOR THE
CONTINUED ACTIVITIES OF THE
GENETIC DISORDERS OF MUCUS
SILLIARY CONSORTIUM AND WATCH
THIS SPACE, HOPE EMPLOYYLY WE
WILL BE VERY SUCCESSFUL WITH
THAT.
I THINK THAT THAT'S IT FOR ME.
THANK YOU.
>> THANK YOU MICHELE.
SO WE WILL MOVE INTO OUR NEXT
SPEAKER WHICH IS DR. NICKERSON
NUTTER.
>> GREAT, I WANT TO THANK THE
ORGANIZERS FOR THE OPPORTUNITY
TO SPEAK TO YOU TODAY ABOUT WHAT
WE'RE DOING AT 3 LAKES
FOUNDATION.
IT WAS A PRIVATE FOUNDATION
STARTED BY A FAMILY WHO LOST A
FAMILY MEMBER TO PULMONARY
FIBROSIS, SO WE'RE A BIT
DIFFERENT FROM THE OTHER
FOUNDATIONS IN THAT WE'RE NOT
FOCUSED SOLELY ON ADVOCACY,
ADVOCACY IS IMPORTANT BUT
LUCKILY THERE ARE OTHER
FOUNDATIONS SUCH AS THE
PULMONARY FOUNDATION AND PF
WARRIORS WHO ARE AVAILABLE TO
PATIENTS AND HAVE GOOD ADVOCACY
FOR PATIENTS.
SO OUR NICHE IS WE'RE MORE
FOCUSED ON THE SCIENCE TO TRY TO
ADVANCE THERAPIES AND ALSO
UNDERSTAND EARLY DISEASE AND
ACCELERATE DIAGNOSIS FOR
PATIENTS.
SO THE NEXT SLIDE.
SO SINCE WE'RE COVERING A LOT OF
DIFFERENT DECS IN THIS WORKSHOP,
I WANT TO BRIEFLY GO OVER IDIO
PATHIC PULMONARY FIBROSIS, SO
THIS IS WHAT THE FAMILY I'M
WORKING WITH ENCOUNTERED AND
THEY HAD CHALLENGES WITH GETTING
AN ACCURATE DIAGNOSIS WHICH IS A
COMMON STORY AND THEY ALSO HAD
TROUBLE WITH OXYGEN AND THEY
WERE NOT VERY GOOD EFFECTIVE
THERAPIES.
THIS WAS ABOUT 10 YEARS AGO.
SO, FOR ANYBODY WHO'S
EXPERIENCED IT, IT'S A CHRONIC
AND PROGRESSIVE DISEASE WHERE
YOU KNOW YOU LOSE THE ABILITY TO
BREATHE, IT'S A RARE DISEASE,
IT'S A RARE DISEASE ABOUT 2
HELPED THOUSAND PATIENTS IN THEP
U.S. AND WHEN PATIENTS ARE
DIAGNOSED, THEY'RE OFTEN TOLD,
YOU KNOW YOU HAVERY
FIBROSIS, SOME PATIENTS MAY NOT
EVEN KNOW WHAT THIS IS AND GO
GET YOUR AFFAIRS IN ORDER
BECAUSE YOU CAN LIVE 2-5 YEARS.
THIS CAN BE OBVIOUSLY
DEVASTATING.
THERE'S ABOUT 30,000 DEATHS PER
YEAR, IT ALSO HAS STRONG GENETIC
COMPONENT OR FAMILIAL COMPONENT
SO IF HAVE YOU A PARENT WHO HAST
6-10 TIMES MORE LIKELY TO HAVE
IT THAN THE GENERAL POPULATION
AND DIAGNOSIS OFTEN IT'S ON NOT
SO MUCH A BIOPSY ANYMORE BUT A
CT SCAN OR HIGH RESOLUTION CT
SCAN AND OFTEN BY THE TIME YOU
GOET TO THE PULL
MONITORROLOGYIST FOR THE CT
SCAN, YOU'VE ALREADY LOST A LOT
OF LUNG FUNCTION AND YOUR
ABILITY TO BREATHE IS ALREADY
GOING DOWN.
SO THE TREATMENTS THERE ARE 2
APPROVED TREATMENTS, THESE WERE
BOTH APPROVED IN 2014, NINTADA
NIB AND PIRFENIDONE, IT'S GREAT
WE HAVE THESE MEDICATIONS BUT
THERE ARE SEERSZ SIDE EFFECTS
AND SOME PATES FIND THEM
INTOLERABLE AND THE OTHER OPTION
IS LUNG TRANSPLANTATION.
SO NEXT SLIDE.
SO I JUST WANTED TO TALK ABOUT
THE DRUG TIMELINE OF PULMONARY
FIBROSIS, WHERE WE'VE BEEN AND
WHERE WE'RE AT.
SO PERFENIDONE WAS DISCOVERED IN
1976 BUT IT WASN'T STUDY AND FOR
THE FIBROTIC PROPERTIES, SO IT
WAS MORE FOR INFLAMMATION AND
THEN IT WAS TESTED IN A
BLEOMYCIN O HAMSTERS WHERE IT
WAS FOUND TO HAVE ANTIFIBROTIC
PROPERTIES.
THERE WAS A CONTROL TRIAL IN
JAPAN, THAT WAS DISCONTINUED IN
2005, BUT THE USE FOR
PERFENIDONE WAS ACCEPTED THEN.
THERE WERE STUDIES THAT SHOWED
EFFECT ON FVC, SORRY, IN 2011
AND THEN BASED ON THE CAPACITY
STUDY AND ANOTHER STUDY CALLED
THE ASCEND STUDY, THE DRUG WAS
WAS APPROVE INDEED 2014.
FOR NINTEDANIB, THE PATH WAS A
BIT SHORTER.
THE DRUG WAS DEVELOPED -- THE
NUMBER FOR THIS DRUG WAS BI1120,
AND IT WAS SHOWN TO HAVE EFFECT
ON LEUKEMIC CELL ASSAYS TO
COLONY FOR THE PURPOSING UNIT
ANDS THERE WAS WAS AN AN LOG
DRUG CALLED BI1000 WHICH WAS
SHOWN TO HAVE ANTIFIBROTIC
PROPERTIES IN A BLEO MOUSE
MODEL.
SO THEN THERE WAS A PHASE 1
STUDY WHERE SAWAWHE FDC
DECLINE IN 2010 AND THERE WERE A
A OTHER STUDIES CALLED THE
IMPULSEUS STUDIES WHERE THEY
SHOWED THE EFFECTS ON FVC WHICH
WERE THE BASIS FOR APPROVAL IN
2014.
NEXT SLIDE, PLEASE.
SO THE GOOD THING WAS THAT THE
DRUGS REALLY DISPLAYED THE
IMPROVEMENT OF THE DRUGS WITH AN
APPROVAL PATHWAY.
HERE WAS THE DRUG PIPELINE IN
2021.
THERE WAS A LOT OF WORK BETWEEN
2014-2021 AND THESE WERE ALL PUT
INTO THE PIPELINE WITH DIFFERENT
MECHANISMS, AND THERE WAS A LOT
OF HOPE FOR PATIENTS
UNFORTUNATELY, NONE OF THESE
HAVE MADE IT ALL THE WAY TO THE
APPROVAL STAGE.
SO WHY IS THAT?
SO YOU CAN GO TO THE NEXT SLIDE.
THIS JUST SHOWS HOW MANY WE
LOST.
I UPDATED IT THIS YEAR.
SO CAN YOU SEE AT THE PHASE 3 WE
LOST ABOUT HALF, WE LOST HALF OF
THE PHASE 2 AND JUST 1 OF THE
PHASE 1.
SO IT'S INTERESTING BECAUSE
PHASE 1 IS OFTEN SAFETY AND YOU
CAN SEE THAT MAYBE WE'RE DOING
BETTER ON SAFETY, GETTING PAST
THE PHASE 1 STAGE BUT WE'RE
LOSING THESE BASED ON EFFICACY
FOR A LOT OF THEM.
SO WHAT'S GOING ON, RIGHT?
BECAUSE CLEARLY WE HAD A
PRECLINICAL PACKAGE WHICH
DEMONSTRATED EFFICACY BUT THE
PROBLEM IS, THESE ARE BASED A
LOT OF TIMES ON CELL BASED
ASSAYS, AND THEN ON RODENT
MODELS, MAINLY BLEOMYCIN MODELS
AND AS WAS DISCUSSED YESTERDAY,
THE RODENT LUNGS ARE VERY
DIFFERENT THAN THE HUMAN LUNG
ANDS MAY NOT BE REPRESENTATIVE
SO WE REALLY, WE NEED TO DO
BETTER THAN THIS.
SO 1 WAY, -- OH, SO THE NEXT
SLIDE, PLEASE.
SO THIS JUST SHOWS THE 1S THAT
HAVE DROPPED OFF AND THEN YOU
CAN JUST GO TO THE NEXT 1 WHICH
SHOWS THE CURRENT PIPELINE.
SO THE GOOD NEWS IS WE HAVE A
FULL PIPELINE BUT AGAIN NOT THAT
MANY ARE MAKING IT ALL THE WAY
AND RIGHT NOW, WE DO HAVE SOME
PROMISING DRUGS IN PHASE 3,
THERE'S A PD4 INHIBITOR, FROM VI
IS AN LPA INHIBITOR FROM BMS,
THERE'S ANOTHER PROMISING
THERAPY FOR TGF BETA COMING OUT
OF [INDISCERNIBLE], SO HOPEFULLY
SOME OF THESE WILL MAKE IT BUT
AGAIN THESE HAVE BEEN DEVELOPED,
THEY'RE PRECLINICAL PACKAGE,
THEY'RE A BIT OLDER SO THEY MAY
STILL BE BASED ON BLEOMYCIN I
KNOW THAT A CLIENT AS SOME
PRECISION LUNG CUT DATA WHICH I
WILL TALK ABOUT IN A MINUTE.
NEXT SLIDE.
SO IN ORDER TO DO BETTER WE NEED
TO GET BETTER MODELS AND
RESEARCH TOOLS.
SO 2 YEARS AGO THERE WAS AN
NHLBI WORKSHOP THAT 3 LAKES
PULMONARY FIBROSIS FOUNDATION
AND NHLBI SPONSORED WHERE WE
BROUGHT TOGETHER EXPERTS IN THE
FIELD AND REALLY ASKED WHAT DO
WE NEED TO DO TO IMPROVE THE
DRUG PIPELINE AND GET THERAPIES
TO PATIENTS.
AND SO THIS IS WHAT WAS
IDENTIFIED.
WE NEED NOVEL MODELS, IT WOULD
BE GREAT TO HAVE THEM BASED ON
HUMAN TISSUE, AND ALSO, CAN WE
HAVE A CENTRAL REPOSITORY FOR
SINGLE CELL ANALYSIS OF TISSUES
AND MODELS AND I WILL MENTION A
LITTLE BIT ABOUT THE IPF CELL
ATLAS AND THE NEXT SLIDE THAT 3
LAKES WAS A PART OF.
ALSO TO UNDERSTAND EARLY DISEASE
IN WAYS TO IMPROVE DIAGNOSIS, TO
UNDERSTAND RISK FACTORS AND THE
DRIVERS, YOU KNOW IF WE CAN
UNDERSTAND THE DISEASE EARLIER
WE CAN BACK UP TREATMENT, MAYBE
WE CAN PREVENT PEOPLE FROM
GETTING SO FIBROTIC.
AND ALSO INPOETICIVATIVE
APPROACHES TO INNOVATIVE TRIAL
DESIGN.
WE REALLY NEED TO START, WE NEED
BETTER END POINTS AS WE'VE
DISCUSSED AND BIOMARKERS AND
IMAGING AND I WILL TALK ABOUT
THAT IN THE NEXT SLIDES.
NEXT SLIDE.
SO THE GOOD NEWS IS IN RECENT
YEARS THERE ARE BEEN REALLY GOOD
TECHNIQUES ANDDELOPED
THE DISEASE MORE,
SO 1 OF THESE SINGLE CELL
SEQUENCING AND SINGULAR
NUCLEOTIDES CLER SEQUENCING AND
SPATIAL TRANSCRIPTOMICS, THIS
COULD GIVE US DISEASE INSIGHTS,
NOVEL TARGETS, BI ONY MARKERS
AND ALSO CLUES OF WHAT WE CAN
LOOK AT IN THE CT SCANS.
THERE'S NOW ALGORITHMS AND NEW
WAYS TO LOOK AT THE HRCT SCANS
AND THERE ARE ALSO COHORT FOR
FIRST DEGREE RELATIVES THAT HAVE
BEEN FOLLOWED FOR A PERIOD OF
TIME THAT CAN GIVE US INSIGHT
INTO EARLIER DEC.
SO NEXT SLIDE.
SO I THINK 1 OF THE KEY ADVANCES
IN THIS FIELD, AND 3 LEGS
WAS THE DEVELOPMENT OF THE IPFT
CELL ATLAS WHICH IS A
COMBINATION OF SINGLE CELL DATA
FROM X-PLANTED IPF LUNGS FROM
SEVERAL LABS AROUND THE CO
INCLUDING NAFTALI KAMINSKI'S
LAB, SO WE'VE TALKED TO
INDUSTRY, EXTENSIVELY USES THIS.
IT'S BEEN USED TO NOT ONLY
UNDERSTAND THE BIOLOGY, BUT ALSO
VALIDATE DRUG TARGETS, IT CAN
ALSO BE USED TO LOOK FOR
BIOMARKERS, SO IT'S BEEN HIGHLY,
HIGHLY USED.
THE DATA I HAVE HERE FOR THE
NUMBER OF USERS IS ACTUALLY A
LITTLE BIT OLD, SO IT'S PROBABLY
MUCH HIGHER THAN THAT.
AND THERE HAVE BEEN KEY
FINDINGS, LIKE THE PRESENCE OF
THESEANT BASALOID CELLS,
TO PROINFLAMMATORY FIBROBLASTS
AND WE'VE ALSO SPONSORED SOME
RESEARCH MORE RECENTLY IN THE
KAMINSKI LAB, TO LOOK AT
PREMATURE AND MATURE LESIONS, SO
INSTEAD OF TAKING THE WHOLE LUNG
AND PARSING OUT THE CELL,
LOOKING AT THE CELLS AND IF
THEY'RE DIFFERENT WHEN THEY'RE
FULLY MATURE AND PHOBE ROTTIC.
AND THEY ALSO DEVELOPED THE IPF
DRUG CONNECT OHM, WHERE YOU CAN
CONNECK THEECS FROM THE
CELL ATLAS SOME REPURPOSED DRUGS
SO CAN YOU MATCH THEM UP AND
FIND DRUGS THAT MIGHT WORK FOR
PATIENTS WITH PULMONARY
FIBROSIS, AND THEN WE ALSO
SPONSORED WORK WITH SINGLE CELL
DATA ON PRECISION CUT LUNG
SLICES THAT HAVE BEEN INDUCED
WITH A FIBROTIC COCKTAIL, TO SEE
HOW THIS MATCHES UP WITH THENHER
STUDYING MORE COMPOUNDS FOR DRUG
DEVELOPMENT AND THIS HAS BEEN IN
COLLABORATION WITH MELANIE KONI
GHOFF, AND OTHERS.
NEXT SLIDE.
SO 1 THING THAT WE'RE REALLY
INTERESTED IN IS SHORING UP SOME
OF THESE RESOURCES, TRYING AS A
FOUNDATION, CAN REALLY HELP MAKE
SOME OF THESE RESOURCES
AVAILABLE FOR DRUG DEVELOPMENT
AND WE FEEL LIKE WE'RE IN A
UNIQUE POSITION.
WE HAVE FUNDED ACADEMIC LABS,
AND I HAVE A BACKGROUND IN DRUG
DEVELOPMENT FROM INDUSTRY WHERE
THERE'S A GAP THERE, WE'VE HEARD
ABOUT THE VALLEY OF DEATH WHERE
ACADEMIC HAS GREAT IDEAS,
INDUSTRY GREAT DRUG DEVELOPERS,
BUT THERE'S A GAP, THERE'S AN IN
BETWEEN AND HOW CAN WE ADDRESS
THIS IN AND 1 THING WE NEED NEED
BETTER TOOLS, SO INDUSTRY
DOESN'T ALWAYS HAVE ACCESS TO
THE HUMAN TISSUE.
YOU KNOW, SOME DO BUT WE'VE BEEN
WORKING WITH INDUSTRY TO
UNDERSTAND THIS GAP, AND 1 THING
IS, IF WE CAN PROVIDE CRYO
PRESERVED TISSUE OR REFRIGERATED
TISSUE, THEN WE CAN CREATE A
SOURCE OF THE TISSUE FOR DRUG
TESTING.
SO WE'VE BEEN WORKING WITH
INDUSTRY TO DEVELOP A CONSORTIUM
WHERE WE WOULD CO-FUND SOME
ASSAYS TO NUMBER 1 VALIDATE THIS
CAN BE DONE, SO RIGHT NOW YOU
CAN BUY THE FROZEN TISSUE BUT
OFTEN YOU DON'T KNOW WHERE IT'S
COMING FROM OR ANYTHING ABOUT
THE PATIENT THAT IT CAME FROM,
YOU KNOW, SO, YOU DON'T KNOW A
LOT ABOUT IT AND EXACTLY WHAT IT
REPRESENTS.
SO THE NEXT SLIDE.
SO SOME STUDIES HAVE BEEN DONE
TO SHOW THIS IS POSSIBLE IN
PUBLIC.
SO A STUDY WITTU THE CRYO
PRESERVING CUT SLICES SHOWSHE
VIABILITY AFTER 7 AND 14 DAYS SO
IT WAS PROPRIETARY METHOD OF
FREEZING THE TISSUE AND THEN
AFTER THAWING IT AT 7 AND 14
DAYS IT WAS COMPARED TO NEVER
FROZEN TISSUE, SO THE VIABILITY
AND PROTEIN CONTENT LOOKED
PRETTY GOOD.
SO THE NEXT SLIDE.
AND THEN THE SECRETION OF
CERTAIN CYTOKINES AND SOME OF
THESE WERE PRESERVED OVER TIME
AND SOME DID NOT PRESERVE AT ALL
AND I THINK THAT'S IMPORTANT.
WE'RE NOT GOING TO GET A PERFECT
REPLICA OF LIVING HUMAN LUNG,
BUT WHAT IS IMPORTANT IS TO KNOW
WHAT THE TISSUE DOES REPRESENT
AND WHAT CAN BE REPRODUCED.
N YOU WOULD KNOW WHAT THE
TISSUE IS USEFUL FOR, SO
INDUSTRY COULD LOOK AND SEE
WHETHER THEIR TARGET IS THERE,
AND WHETHER THEY CAN ACTUALLY
USE THIS FROZEN TISSUE.
SO NEXT SLIDE.
THIS SLIDE JUST SHOWS THE
CELLULAR DIVERSITY THAT'S
MAINTAIN AND AGAIN SOME CELL
TYPES SUCH AS AT2 ARE LOWER IN
ABUNDANCE AFTER YOU FREEZE AND
THAW THE TISSUE, WRASSE OTHERS
LIKE FIBROBLASTS ARE A BIT
OVERREPRESENTED. NEXT SLIDE.
NOW, WORKING WITH
INDUSTRY PARTNERS, THE STUDY
PLAN IS TO GET TISSUE FROM 3
FIBROTIC LUNGS, WITH MULTIPLE
SECTIONS TO ASSESS THE
VIABILITY, PROFIBROTIC
SECRETION, CELLULAR COMPOSITION,
AND ALSO TO LOOK AT THE --
WHAT'S ALSO IMPORTANT AND AGAIN
TO BRIDGE THE GAP BETWEEN
ACADEMIC AND INDUSTRY IS HOW DO
THESE DRUGS ACT IN THESE MODELS.
SO IT'S IMPORTANT TO RUN DOSE
RESPONSE CURVES AND REALLY
UNDERSTAND.
SO ESPECIALLY STANDARD OF CARE,
SO NINTEDANIB, AND THE ALK5
INHIBITOR AND THEN ROUGH ATOM
FIBROTIC COCKTAIL ISSUES AS
WELL.
WE WILL CAREFULLY COLLECT THEM
SO WE KNOW FROM WHAT PART OF THE
F THEY ARE FROM AND HOW
FIBROTIC THEY ARE.
SO NEXT SLIDE.
SO ANOTH THAT 3 LAKES IS
VERY INTERESTED IN IS
UNDERSTANDING EARLY DISEASE.
SO THE EARLIER WE CAN DIAGNOSE,
THIS JUST SHOWS THAT BY THE TIME
YOU'RE DIAGNOSED, YOU'RE PRETTY
FIBROTIC SO IF WE COULD DIAGNOSE
EARLIER AND TREAT EARLIER,
THAT'S THE ONLY WAY WE'RE GOING
TO GET TO A CURE, SO HOW ARE WE
GOING TO DO THAT?
WHEN THE END POINT RIGHT NOW IS
FVC, SO WE NEED BETTER
BIOMARKERS AND END POINTS TO DO
THIS.
SO 2 THINGS WE NEED TO
UNDERSTAND THE DISEASE AND
DEVELOP BIOMARKERS AND END
POINTS.
SO NEXT SLIDE.
SO WE'VE BEEN WORKING WITH JOHN
[INDISCERNIBLE] AND NICK
[INDISCERNIBLE] IN A STUDY WE
CALL 1 POINT FO, THEY HAVE CT
SCANS FROM OVER 10 YEARS AGO,
SOME ARE 12 TO 14 YEARS AGO, SO
IF YOU LOOK AT THE LEFT, THERE'S
2 LINES THAT START OUT, SO THEY
EITHER HAD ILAs OR THEY HAD NO
FINDINGS WHATSOEVER.
AND AS IT GOES TO THE RIGHT WHEN
IT DROPS DOWN, SOME OF THESE
PEOPLE HAVE DIRECTINGED, THEIR
DISEASE HAVE PROGRESSED AND SOME
OF THEMHE PULMONARYS,
SO WE CAN TAKE THESE AND PUT
THEM INTO BUCKETS BECAUSE WE CAN
LOOK BACK, SO WE SELECTED0
SAMPLES FROM EACH GROUP AND DID
SINGLE CELL ANALYSIS AND HERE WE
SHOW REPRESENTATIVE WORK ON AT2
MOLECULES AND YOU CAN JUST SEE
THEY'RE DIFFERENT.
SO WHAT THIS SHOW SYSTEM THAT
THERE ARE MOLECULAR DIFFERENCES
VERY EARLY ON THAT PROCEED WHAT
WE CAN PICK UP IN THE CT SCANS.
SO IF WE CAN FIND BIOMARKERS
THAT WE CAN THEN DETECT IN THE
BLOOD, MY DREAM WOULD BE YOU GO
INTO THE DOCTOR, YOU A BLOOD
TEST, IF YOU HAVE A FAMILY
MEMBER, YOU'RE AT RISK, THEN YOU
GO GET A CT SCAN SO YOU CAN GET
DIAGNOSED MUCH EARLIER AND IF WE
UNDERSTAND THE BIOLOGY OF WHAT'E
DRUGGINGS OUT THERE THAT --
DRUGS THAT CAN ACTUALLY TREAT
EARLIER.
NEXT SLIDE.
SO THERE HAS BEEN SOME
BIOMARKERS, WE STILL HAVE A LONG
WAY TO GO.
THESE ARE THE BIOMARKERS THAT
HAVE BEEN IDENTIFIED, I WON'T GO
THROUGH THEM ALL, SOME OF THEM
ARE FIBROTIC DECS, DIAGNOSTIC,
PROGNOSTIC THAT PREDICT THE
OUTCOME AND SOME IN RESPONSE TO
THERAPY BUT NONE OF THESE HAVE
BEEN APPROVED FOR CLINICAL
TRIALS AND AGAIN AS DISCUSSED
EARLIER, WE PROBABLY NEED A
PANEL OF BIOMARKERS WITH
BIOMARKERS ALONE WILL DO THE
JOB.
NEXT SLIDE.
SO THERE ARE SOME STUDIES ON
COMBINATIONS, 1 OF THE FIRST
STUDIES WAS FROM IVAN ROSAS IN
COLLEAGUES IN 2008 WITH MMP 7,
MPP1 AND MMP8, AND IGFP1 AND
TGF-RECEPTOR AND YOU CAN SEE
THAT SOME OF THESE HAVE BEEN
REPEATED OVER AND OVER.
THERE'S HAVE BEEN A COUPLE OTHER
STUDIES BUT AGAIN, NOTHING YET
HAS MADE IT TO THE POINT THAT IT
HAS BEEN REPRODUCED AND CAN BE
USED AS A CLINICAL EITHER
COMBINATION OF BIOMARKER AND TO
DO THIS WE'RE GOING TO NEED TO
VALIDATE IT IN MULTIPLE COHORTS
OF PATIENTS.
SO THE NEXT SLIDE.
SO THERE'S A PROLIFIC CONSORTIUM
WHICH IS EXACTLY WHAT THEY'RE
TRYING TO DO, IT'S A NUMBER OF
INDUSTRY MEMBERS AND 3 LAKES IS
PARTICIPATING IN THIS AS WELL AS
THE PULMONARY FIBROSIS
FOUNDATION, SO THEY IDENTIFY 12
BIOMARKERS FROM THE LITERATURE
AND REALLY VALIDATED ASSAYS AND
THEN LOOKED FOR THEM AND
COMPARED THEM TO PREDICTED FVC
TRANSPLANT-FREE SURVIVAL AND
DEATH AND LUNG TRANSPLANT AND
THE 1 THAT ROSE TO THE TOP IS
SPD AND THERE'S OTHERS 1S BUT
E NOT L AT A COUPLE
OTHER COHORTS TO TRY TO
REPRODUCE THIS DATA BECAUSE
THEY'RE REALLY TRYING TO FIND
SOMETHING THAT THEY CAN THEN USE
AS A VALIDATED END POINT IN
CLINICAL TRIALS.
NEXT STUDY.
NEXT SLIDE, SORRY.
SO WE NEED MORE VALIDATED
BIOMARKERS FOR BOTH EARLY AND
ESTABLISHED DISEASE SINCE FVC IS
THE ONLY APPROVED BIOMARKER AND
IF WE WANT TO TREAT EARLIER,
THERE WON'T BE ANY CHANGES IN
FVC SO WE HAVE TO COME UP WITH
SOMETHING.
HRCT SCANS, WE'VE HEARD ABOUT
THAT AND THOSE ARE LINKED TO
PROGNOSIS BUT YET HAVE NOTN
VALIDATED YET.
THERE'S WORK TO DO THAT BUT WE
HAVE A WAYS TO GO.
SINGLE BIOMARKERS MAY NOT BE
SUFFICIENT, WE MAY NEED A
COMPOSITE BIOMARKER AND A LOT
MORE WORK NEEDS TO BE DONE IN
THIS AREA AND THERE ARE OTHER
THINGS THAT COULD POSSIBLY USE
AS BIOMARKERS SUCH AS BREATH,
VOLATILE, ORGANIC COMPOUNDS OR
EXOSOMES.
NEXT SLIDE.
SO I JUST WANTED TO END WITH A
FIGURE THAT CAME OUT OF THE
PROCEEDINGS FROM THE NHLBI
WORKSHOP THAT WAS HELD ON
PULMONARY FIBROSIS IN 2022 WHICH
REALLY SUMMARIZES THE GAPS IN
THE FIELD AND WHERE WE NEED TO
GO.
AND THAT'S -- YOU KNOW THE
MODELS THAT WE'VE HEARD ABOUT
UNDERSTANDING EARLY DEC AND RISK
FACTORS, CLINICAL TRIALS AND
BIOMARKERS.
THREE LAKES IS PROUD OF THE
DIFFERENCE THEY'VE MADE IN THIS
FIELD AS A PRIVATE FOUNDATION
AND AS A PRIVATE FOUNDATION
WE'VE NOT HAD OTHER PEOPLE YOIN
US IN THIS MISSION SO I WANTED
TO LET PEOPLE KNOW THAT IN 2025,
WE'RE PLANNING TO CHANGE INTO A
PUBLIC FOUNDATION SO HOPEFULLY
OTHERS WILL JOIN US ON THIS
MISSION AND WE CAN CONTINUE THIS
WORK. .
THANK YOU.
>> THANKS SHERYL, LOOKING
FORWARD TO TALKING TO YOU DURING
THE PANEL DISCUSSION, WE WILL
MOVE INTO THE LAST SPEAKER OF
THIS SESSION, DR. Mc CORMAC K.
>> OKAY, THANK YOU.
I WOULD LIKE TO THANK ALL THE
ORGANIZERS FOR THE OPPORTUNITY
TO TELL YOU ABOUT PROGRESS IN
LAM, AND THIS IS THE STORY OF A
GRASS ROOTS EFFORT LAUNCHED BY A
MOTHER FOR THE BENEFIT OF HER
DAUGHTER, NOT UNLIKE THE STORY
MICHELLE MANNION WAS TELLING
WHICH LED TO AN EFFECTIVE
THERAPY.
NEXT SLIDE, PLEASE.
MY CONFLICTS THAT ARE RELEVANT
TO TODAY'S TALK INCLUDE A
FEDERAL AND UNRESTRICTED
INDUSTRY GRANTS, A PAT EPT FOR A
DIAGNOSTIC BIOMARKER CALLED
VEG-FD, ALL ROYALTIES ARE
DIRECTED TO OUR INSTITUTION AND
DONATION OF DRUGS BY PHARMA FOR
TRIALS.
NEXT SLIDE PLEASE.
MY FRAME OF REFERENCE IS THAT IA
WAS THE FOUNDING SCIENTIFIC
DIRECTOR OF THE LAM FOUNDATION
AND SERVED IN THAT ROLE FOR 25
YEARS THROUGH JANUARY OF 2021,
VOLUNTARILY AND I WAS THE
PRINCIPAL INVESTIGATOROT TRIAL
EMPLOY I WAS DISCUSSING THE
MILES TRIAL, I WILL BE
DISCUSSING, MY PRIMARY OBJECTIVE
IS TO HIGHLIGHT THE ROLE OF
ADVOCACY BY THE LAM FOUNDATION
AND PROGRESS.
NEXT SLIDE, PLEASE.
IT'S IMPORTANT I TELL YOU ABOUT
THE RARE LUNG DISEASE
CONSORTIUM, MICHELLE ALSO HAD
SLIDES ABOUT THIS FOR A PERIOD
OF ABOUT 15 YEARS, WITH A GAP IN
THE MITTED, BRUCE AND I WERE
AWARDED A GRANT FROM NCATS AND
NHLBI TO ESTABLISH A RARE LUNG
DEC CLINICAL NETWORK OF ABOUT 75
CLINICS AROUND THE WORLD THAT
FOCUS REFERRALS TO 1 OR 2
ACADEMIC INSTITUTIONS WITHIN
POPULATION CENTERS FOR THE
PURPOSE OF NURTURING EXPERTISE,
FACILITATING EXPERT CLINICAL
CARE AND CONDUCTING RESEARCH.
IT WAS THROUGH THIS NETWORK THAT
MOST OF THEMOAM TRIALS HAVE BEEN
CONDUCTED AND ALSO TRIALS IN
[INDISCERNIBLE] AND
[INDISCERNIBLE].
THE NETWORK STARTED ON A
PLATFORM OF CLINICS WHICH
EXPANDED THEIR SCOPE OF INTEREST
TO INCLUDE ABOUT 2 DOZEN OTHER
RARE LUNG DECS SOME OF WHICH ARE
REPRESENTED BY PATIENT ADVOCACY
ORGANIZATION SHOWN IN RED AND IN
BOLD RED FOR THOSE THAT HAVE
STRONG PATIENTA ADVOCACY
ORGANIZATIONOCNI ASSOCIATE WIDE
THEM.
NEXT SLIDE PLEASE.
SO LAM IS AN UNCOMMON AND FATAL
PROGRESSIVE DEC IN YOUNG WOMEN,
CHARACTERIZED BY SMOOTH MUSCLE
CELL INFILTRATION AND CYSTIC
DESTRUCTION OF LUNG TISSUE, ON
THE IMAGE ON THE RIGHT
HIGHLIGHTS THE CYSTS AND IT'S
EASY TO APPRECIATE HOW
TREMENDOUSLY DISSTRUCTURALLYIVE
THIS CAN BE TO LUNG
ARCHITECTURE.
NEXT SLIDE, PLEASE.
SO LAM OCCURS MOSTLY IN WOMEN AT
AN AVERAGE AGE OF ABOUT 35 YEARS
WITH A RAINCHL FROM 3-85 IN THE
LITERATURE.
THERE ARE MEN WHO ARE AFFECTED
BUT ONLY A FEW SYMPTOMATIC MEN
THAT I'VE EVER BECOME AWARE OF.
IT AFFECTS ABOUT 25 WOMEN PER
MILLION WOMEN.
THE RATE OF LUNG FUNCTION
DECLINE BASED ON FEV1 IS ABOUT
3-15% PER YEAR IN MOST PATIENTS.
SUCH THAT WITHIN 10 YEARS OF
SYMPTOM ONSET, 55% OF THE
PATIENTS ARE BREATHLESS, 20%
ONOXIEN AND 10% ARE DECEASED.
THE MEDIAN SURVIVAL IN EARLY
STUDIES WAS ESTIMATED TO BE
ABOUT 8 AND HALF YEARS BUT IT'S
BECOME CLEAR THROUGH POPULATION
BASED STUDIES THAT IT'S CLOSER
TO 25 YEARS.
THERE IS NO CURE FOR THIS
DISEASE TO THIS DATE.
THE IMAGE AT THE TOP WAS A
FORMERLY HEALTHY PATIENT AND
DISCOVERED SHE WAS 16 WEEKS
PREGNANT BY URINE DIP STICK AT
HOME AND SUFFERED A PNEUMOTHORAX
THE NEXT DAY AND A KOBT
RALATERAL PNEUMOTHORAX AND SHE
WAS HOSPITALIZED FOR HER ENTIRE
PREGNANCY.
SHE WENT HOME TO OXYGEN AS YOU
CAN SEE AND SHE REQUIRED A LUNG
TRANSPLANT A FEW YEARS LATER AND
YOU CAN SEE IN THE BOTTOM IMAGE
SHE'S A BIT CURBINGOID AND HER
DAUGHTER'S MAYBE 4 OR 5 YEARS
OLD.
THAT CHILD IS NOW 35 YEARS OLD,
THE MOM HAD A SECOND LUNG
TRANSPLANT, THIS CASE
DEMONSTRATES THAT LAM CAN RESULT
IN RESPIRATORY FAILURE
ACCELERATE BIDE HORMONAL
INFLUENCES.
NEXT SLIDE, PLEASE.
ANDREA BURNS WAS THE INSPIRATION
FOR THE LAM FOUNDATION.
SHE IS A YOUNG LADY FROM
CINCINNATI WHO DEVELOPED CHEST
PAIN ON A FLIGHT TO DENVER IN
1984.
SHE WAS RESUSCITATED ON THE
TARMAC IN DENVER AND FOUND TO
HAVE A COLLAPSED LUNG, A CHEST
TUBE WAS PLACED IN THE COLORADO
EMERGENCY ROOM AND A CT SCANNED
DIFFUSE CYSTIC LUNG DISEASE, SHE
TOLD THE SURGEON SHE HAD HAD A
RARE KIDNEY TUMOR REMOVED BEFORE
AND HE WAS ABLE TO TELL HER WHAT
THE PHYSICIANS IN CINCINNATI HAD
NOT TOLD HER, THAT BASED ON
THOSE 2 FINDINGS, AND WHERE THE
KIDNEY TUMOR AND THE CYSTIC
DISEASE AND THAT SHE HAD LAM AND
HE RECOMMENDED SHE SEE ME WHEN
SHE RETURNED TO CINCINNATI AS I
HAD JUST MOVED TO CINCINNATI.
NEXT SLIDE ISSUE PLEASE.
LUCKY FOR HER, HER MOTHER IS SUE
BURNS WHO ESTABLISHED THE
FOUNDATION IN HER HONOR.
SHE MET WITH 9 LAM PATIENTS IN
HER HOME IN THE EARLY 90S.
SHE FOWBDED THE FOUNDATION IN
HER BASEMENT AND ASKED ME TO
SERVE AS HER VOLUNTEER
SCIENTIFIC DIRECTOR.
SHE READ AN ARTICLE SUGGESTING
CRITICAL NEED FOR REGISTRY BY
DOCTORS TAYLOR AND RUE AND
COLBY.
SHE MARSHALED A LETTER WRITING
CAMPAIGN TO THE NIH AND DRNG
INCLUDING PULMONARY PHYSICIANS
ACROSS THE U.S.
USING ALL OF OUR STUDENTS AT
SAINT MICHAELS WHERE SHE TAUGHT
MUSIC AND HER HUSBAND WAS A
FOOTBALL COACH AND USING THIS
TYPE WRITER SHOWN ON THE PANEL
ON THE BOTTOM.
SHE TESTIFIED BEFORE CONGRESS
AND ULTIMATELY [INDISCERNIBLE]
WHO WAS THEN THE NHLBI DIRECTOR
INVITED HER TO COME TO THE NIH
AND TOLD HER HE WOULD COMMISSION
AN NIH REGISTRY AND AN
INTRAMURAL LAM PROTOCOL FROM
THAT POINT FORWARD AND THE
INTRAMURAL PROTOCOL WAS STILL IN
PLACE TO THIS DAY.
NEXT SLIDE, PLEASE.
SO, SUE AND FRAN FOUNDED THE
NOWNDATION IN 1995 AND OVER THE
NEXT 20 YEARS I WAS INVOLVED,
THEY RAISED 18 MILLION-DOLLAR
AND DEVOTED 12 MILLION OF THAT
TO RESEARCH AND FUNDED 155
RESEARCH GRANTS.
THEY HELD ANNUAL LAM CONFERENCE
IN CINCINNATI WHICH WAS FUNDED
EVERY YEAR BY AN NHLBI R13 GRANT
WHICH CONVENED ABOUT 150 LAM
PATIENTS AND ABOUT A HUNDRED
INVESTIGATORS IN THIS UNIQUE
ISHT ACTIVE FORUM WHERE THE
PATIENTS ARE WELCOME IN THE
SCIENTIFIC SESSIONS AND INVITED
TO ASK QUESTIONS THERE AND THE
INVESTIGATORS AND CLINICIANS ARE
UPDATING THE PATIENTS ON
SCIENTIFIC ADVANCES ALL ON THE
SAME SETTING AND IT ENDS WITH A
FUNDRAISING EVENT THAT USUALLY
GENERATES SOMEWHERE IN THE
NEIGHBORHOOD OF 150 TO $200,000
OR MORE.
NEXT SLIDE PLEASE.
SO THE PATH FOR PROGRESS IS
FAMILIAR TO ALL THE DISEASE
GROUPS ON THIS CALL AND IT
INCLUDED THE ROLE OF THE
FOUNDATION ORGANIZING PATIENTS,
MOTIVATING INVESTIGATORS,
PROVIDING SEED FUND THAGOREAN
IDENTIFIED THE GENE, PROTEIN,
PATHWAY AND ULTIMATELY THE
THERAPEUTIC TARGET OF COURSE IN
CONCERT WITH NIH STUDIES AND
FOLLOWED BY PRECLINICAL STUDIES,
PHASE 1-2 TRIALS AND A PIVOTAL
TRIAL THAT IDENTIFIED AN
EFFECTIVE THERAPY.
NEXT SLIDE, PLEASE.
EARLY LAM FOUNDATION RESOURCES
ARE SHOWN HERE.
THE LAM CLINIC NETWORK HAS BEEN
CONDUCTING QUARTERLY CASE
MANAGEMENT CALLS AND COOPERATIVE
STUDIES FOR OVER A DECADE AND AS
I MENTIONED WAS THE PLATFORM FOR
THE RARE LUNG DEC CONSORTIUM,
THE NHLBI REG TREE AND
INTRAMURAL PROGRAM HAS MADE
SUBSTANTIAL CONTRIBUTIONS TO OUR
UNDERSTANDING OF LAM AND DEFINE
THE NATURAL HISTORY OF THE
DISEASE REVEALING THAT THE
AVERAGE RATE OF LUNG FUNCTION
DECLINE IS ABOUT 90-MILLILITERS
IN FEV1 PER YEAR WHICH IS ABOUT
3 TIMES NORMAL AND MEDIAN
SURVIVAL FROM TIME OF DIAGNOSIS
OF OVER 20 YEARS, PROBABLY ON
THE ORDER OF 25 YEARS.
LAM LIAISONS ARE A PATIENT
NETWORK THAT CONVENE REGIONAL
MEETINGS AND ADVISE THE
FOWNATION FOR PRIORITIES
RESEARCH.
NEXT SLIDE, PLEASE.
SO A LITTLE BIT MORE ABOUT LAM,
IT'S A LOW GRADE HORMONEALLY
RESPONSIVE NEUROECTODERMALY
PLASM THAT CAUSES SYSTEMIC
DISSTRUKS OF THE LYMPHATICS IN
THE LUNG.
SHOWN IN THIS FORMULARY
REFERENCE FILE IN THE LOWER LEFT
OF THE CT OF THE LUNG IN THE
UPPER RIGHT, [INDISCERNIBLE]
SHOWN IN THE PANEL IN THE
MIDRIGHT, AND THE MILKY FLUID
THAT APPEARS WHEN THE CHEST IS
TAPPED, SHOWN ON THE INSET, THE
GENES WERE IDENTIFIED IN
PATIENTS WITH TUBELER O
CLEROSEIS WHICH WAS SHOWN IN LAM
BY ELIZABETH [INDISCERNIBLE] AND
THE mTOR PATHWAY AND MOLECULAR
TARGETS WERE WORKED OUT IN FRUIT
FLIES AND BY [INDISCERNIBLE] AND
OTHERS INVESTIGATORS, THE mTOR
PATHWAY IS CENTRAL TO CELLULAR
METABOLISM, INCLUDING CELL
PROLIFERATION, AND LIMP ANG O
GENESIS, AND AT THE TIME OF
THESE FINDINGS THERE WERE 2 ORAL
INHIB THORS UTRORS APPROVED FOR
TRANSPLANT REJECTION THAT WERE
AVAILABLE FOR PREPURPOSING.
NEXT SLIDE, PLEASE.
SO ALTHOUGH A IN LECULAR TARGET
HAD BEEN IDENTIFIED THERE WERE
mTOR INHIBITORS AVAILABLE FOR
REPURPOSING AND A PHASE 1 TRIAL
HAD SHOWN A PROMISING SIGNAL IN
THE LUNG AND PATIENTS WERE
ORGANIZED AND EDUCATED ABOUT THE
IMPORTANCE OF TRIALS BY THE
FOUNDATION, NO PHARMACEUTICAL
FIRM WAS WILLING TO STEP FORWARD
TO CONDUCT THE TRIAL IN SUCH A
RARE CONDITION.
SO A GROUP OF PHYSICIAN
INVESTIGATORS AROUND THE WORLD
ORGANIZED TO CONDUCT THIS
INVESTIGATOR INITIATED
RANDOMIZED DOUBLE BLIND CONTROL
TRIAL OF THE mTOR, VERSUS
PLACEBO IN 89 PATIENTS CALLED
MILES, THE LAM FOUNDATION
PROMOTED THE TRIAL AND ASSISTED
WITH ENROLLMENT.
THEY INVESTED ABOUT HALF THEIR
NETWORK AT THE TIME FOR THIS
TRIAL THAT COST WELL OVER
$5 MILLION, THEY PUT IN OVER A
HALF MILLION THERE IS AND MANY
OTHER FUNDERS INCLUDING UC,
CHILDREN'S HOSPITAL, FDA,
PFIZER, TUMOR SPECTRUM CLER O
SCLEROSIS ALLIANCE, NIH, THERE
WERE 12 SITES AND 3 COUNTRIES.
UNIVERSITY OF CINCINNATI WAS THE
HUB, AND THE LAMB FOUNDATION
PROVED BE MORE FACILE AT
HANDLING INVOICES SO THEY TOOK
OVER THAT FUNCTION.
THE TRIAL TOOK SEVERAL YEARS TO
ENROLL, OVER 3 YEARS AND WHEN
RECRUITMENT LAGGED LISA YOUNG IN
THE LAB IDENTIFIED A DIAGNOSTIC
BIOMARKER CALLED VEG FD IN THE
LOWER RIGHT PANEL THAT ENABLED
TO TO DISCRIMINATE LAM FROM
OTHER MIMICS AND ALLOWED
PATIENTS TO ENROLL WITHOUT THE
NEED FOR A LUNG BIOPSY WHICH
REALLY BOOSTED ENROLLMENT.
WHEN DATA WAS ANALYZED IN THE
PANEL IN THE UPPER RIGHT IT WAS
ASHES PARENT THE PATIENTS ON
PLACEBO LOST ABOUT 11% OF THE
THEIR LUNG FUNCTION IN THE FORM
OF FEV1 IN THE FIRST YEAR WHILE
THOSE ON SIROLMOBOIS, IT
IMPROVEMENT.
THERE WAS A REDUCTION IN VEG FD.
IN THE SECOND YEAR WHEN THE
PLACEBOS WERE HELD, LUNG
FUNCTION DECLINE RESUMED IN THE
[INDISCERNIBLE] GROUP PARALLEL
WITH THAT WITH THE PLACEBO
GROUP.
THESE RESULTS WERE PUBLISH
INDEED 2011.
IT'S IMPORTANT TO NOTE THAT
THROUGHOUT THE 3 YEARS THAT
MILES WAS ENROLLING IT WAS
ALREADY CLEAR THAT mTOR
INHIBITORS WERE VERY PROMISING
FOR LAM AND AVAILABLE BY
PRESCRIPTION FROM ANY DOCTOR AND
A TRIP TO THE PHARMACY.
YET, THESE PATIENTS SIGNED UP
FOR A 2 YEAR COMMITMENT RISKING
LOSING 20% OF THEIR LUNG
FUNCTION WHILE THEY WERE ON THE
STUDY IF THEY WERE IN THE
PLACEBO GROUP.
AND THE REASON THAT WE HAVE AN
APPROVED THERAPY FOR LAM IS THAT
THESE COURAGEOUS PATIENTS
COMMITTED TO THE ENTIRE 2 YEAR
COURSE OF THE TRIAL INCLUDING
OBSERVATION YOU'RE ON NO THERAPY
AND REMAINED ON THE STUDY FOR
THE DURATION.
NEXT SLIDE, PLEASE.
OH, I'M SORRY THAT THAT WAS THE
WRONG SLIDE.
THEY DECLINED BASED ON THE
RARITY OF LAM AND THE WANING
PATENT LIFE OF THE DRUG, BY THAT
TIME WE HEARD ABOUT AN
ALTERNATHWAY TOALL
THE COMPANY TO CHANGE A LABEL
FOR THE DRUG CALLED THE
CITIZEN'S PETITION, THEY DIDN'T
LIKE THAT PATHWAY BECAUSE
MILESTONES ARE NOT REDINED SO
THE FDA THEMSELVES REACHED OUT.
SO LAM FOUNDATION, PFIZER AND I
MET WITH THE FDA, TO CHART A
COURSE FOR SIROLIMUS, FOR ORPHAN
DRUG, BREAK THROUGH
DEZITIONINATION AND SUBMISSION
OF A SUPPLEMENT AT NDA AND WE
SENT OUR APPLICATION IN ON
CHRISTMAS EVE ON 2014 AND WE
RECEIVED APPROVAL IN UNDER 6
MONTHS.
NEXT SLIDE, PLEASE.
WE ARE VERY PROUD TO HAVE
FRANCIS COLLINS CITE THE LAM
FOUNDATION AN EXEMPLAR PROGRESS
FOR IMMUNITY ON THE NIH RARE
DISEASE DAY, IN 2016.
NEXT SLIDE, PLEASE.
FDA APPROVAL TURNED OUT TO BE A
REMARKABLE CATALYST FOR A PROVAL
BY THE GOVERNMENTAL AGENCIES IN
40 OTHER COUNTRIES, INCLUDING
SOME WHERE THE DRUG IS ONLY
AVAILABLE IF THEY HAVE
GOVERNMENTAL APPROVAL.
IT'S NOW APPROVE INDEED JAPAN,
RUSSIA, SOUTH KOREA, BRAZIL,
MANY COUNTRIES IN SOUTH AMERICA.
HONG KONG, EUROPEAN UNION.
WE BELIEVE THAT HALF OF ALL
PATIENTS WITH ACCESS TO THE DRUG
ARE CURRENTLY TAKING IT.
NEXT SLIDE, PLEASE.
IT'S USEFUL TO REVIEW THE KEY
INGREDIENTS THAT RESULTED IN A
TARGETED TREATMENT FOR LAM AND I
THINK NUMBER 1 IS THE POWER OF
ACADEMIC HEALTH CENTERS, THE
EXPERTISE AND RESOURCES OF MAJOR
ACADEMIC HEALTH CENTERS, MAKE
THIS POSSIBLE, NO DRUG COMPANY
WAS WILLING TO DO THIS RESEARCH,
AND IT WAS THROUGH THE ALTRUISM
OF PHYSICIAN INVESTIGATORS AND
MANY OTHERS THAT WE WERE ABLE TO
LAUNCH THIS TRIAL.
THE COURAGE AND RESOLVE THE
PATIENTS WHO ORGANIZED TO
FACILITATE AND FUND RESEARCH AND
THEN LINED UP FOR TRIALS,
FUNDING OF EXCELLENT RESEARCH
PLIEND TO IMMEDIATE RELEVANCE,
BASIC RESEARCH IN FRUIT FLIES,
WORMS AND RODENTS REALLY
IDENTIFIED MOLECULAR TARGET FOR
THIS DISEASE, THE ALTRUISM OF
NOT ONLY MEDICAL CAREGIVERS BUT
INDUSTRY AND REGULATORS, WE HAD
TREMENDOUS SUPPORT FOR NO
COMPENSATION FROM PFIZER, FDA
AND REGULATE ARES THAT HELPED US
GET TO THE GOAL LINE.
ASK ACCESS TO FUNDING USUALLY
AGENCIES ARE NOT HAPPY ABOUT
SHARING, FUNDING FOR A TRAIL
LIKE THIS BUT WE HAD I THINK A
DOZEN FUNDERS FOR THIS TRIAL
EACH WILLING TO SUPPORT A
PORTION OF IT AND FINALLY
GOVERNMENT ADVOCACY THAT
HAPPENED WELL BEFORE THE TRIAL
STARTED INCLUDING THE RARE
DISEASE ACT OF 2002 WHICH
PROVIDED THE RARE LUNG DISEASE
INFRASTRUCTURE THAT MADE AN
INTERNATIONAL INVESTIGATOR
INITIATED TRIAL IN LAM.
NEXT SLIDE, PLEASE.
SO SINCE THE MILES TRIAL,
THERE'S BEEN CONTINUING
PROGRESS.
THE MILES REGISTRY WAS
ESTABLISHED ABOUT 7 YEARS AGO,
THIS IS A REAL WORLD OBSERVAL
REG TREE TO COLLECT LONGITUDINAL
DATA ON THE NATURAL HISTORY,
LONG-TERM SAFETY AND EFFICACY OF
SIROLMUS THERAPY.
LAM'S FOUNDATION HAS BEEN
ASIEVING WITH ENROLLMENT FROM
THIS PROJECT FROM THE BEGINNING
AND WE SUPPORTED MIDAS AS THE
FUNDING RAN OUT.
THE FIRST REPORT WILL BE IN 2025
AND A QUICK LOOK AT PRELIMINARY
DATA SHOWS THERE'S REMARKABLE
STABILITY OF FAV 1 IN PATIENT
WHO IS ARE TAKING SIROLIMUS
DRUG.
WE ARE NOW WORKING ON A TRIAL
CALLED MILED, AND IF
PROPHYLACTIC EARLY LOW DOSE
PREVENTS PROGRESSION TO MORE
ADVANCED STAGES IN PATIENTS WITH
MILD LAM.
WE'VE HAD 10 SITES, THE LAM
FOUNDATION HAS BEEN PAYING FOR
TRAVEL AND ASSISTING WITH
ENROLLMENT AND WE SHOULD HAVE A
REPORT OUT THIS COMING YEAR.
OTHER -- IN ADDITION TO THE
ANNUAL SEMIANNUAL LAM POSEIUM I
MENTIONED, LAM FOUNDATION, 1
SLIDE FORWARD -- THE LAM
FOUNDATION HAS HAD A NUMBER OF
INNOVATIVE ESPECIALLY
CONFERENCES INCLUDING THOSE
DEVOTED TO BIOMARKER, BIOMARKERS
AND OTHER NICHE AREAS BUT 1 OF
MY FAVORITES WAS THE PATIENT
BENEFIT CONFERENCE WHICH BEGAN
WITH SURVEYS TO ASK PATES WHAT
THEIR PRIORITIES FOR RESEARCH
WERE AND A WORD CLOUD WAS
DEVELOPED TO REPRESENT THE
FREQUENCY OF WORDS THAT WERE
REPEATED IN THE SURVEY, 6 FOCUS
AREAS WERE CHOSEN, EXPERTS AND
COMPANIES IN THOSE AREAS WERE
RECRUITED AND 8 PROJECTS WERE
FUNDED FROM THE 200,000 THERE IS
THAT WAS RAISED DURING THE
EVENT.
THERE ARE STUDIES UNDERWAY TO
ADDRESS FATIGUE, EXERCISE,
OXYGEN DELIVERY, COPING AND
BIOMARKERS.
THE I THINK THE PATIENT
COMMUNITY APPRECIATED THAT IN
ADDITION TO OUR BASIC CLINICAL
TRIALS.
FOWBDATION WAS FOCUSING ON THE
PROBLEMS THAT AFFECT THEIR DAILY
LIVES.
NEXT SLIDE, PLEASE.
THE LAM FOUNDATION AWLINGS
PROVIDED SEED FUNDING TO GET
GUIDE LINES STARTED.
IN THESE GUIDE LINES WE'VE
INCORPORATED RECOMMENDATIONINGS
FOR THE USE OF VEG FD AS A
DIAGNOSTIC BIOMARKER THAT CAN
OBVIATE THE NEED FOR BIOPSY AND
THE INDICATIONS FOR THE USE OF
SIROLIMUS, AND THE DOCUMENTS
HELP TO DISSEMINATE NEW
INFORMATION ABOUT MANAGEMENT AND
TREATMENT.
NEXT SLIDE, PLEASE.
FINALLY, THE LAM FOUNDATION
RECOGNIZED THE POWER OF THE NEW
SINGLE SRNARE--ADMINISTRATIVE
SEQ TECHNOLOGY THAT THE LAST
SPEAKER WAS TALKING ABOUT AND
FUNDED THE TRANSCRIPTOMIC
PROFILE OF FROM LUNG PATIENTS
WHO HAD BEEN TRANSPLANTED.
WHEN THE LUNG WAS DISASSOCIATED
INTO INDIVIDUAL CELLS THEY WERE
CLUSTERED ON SIGNATURES IT
BECAME APPARENT THERE WAS AN
ECTOPIC POPULATION THAT'S NEVER
BEEN IDENTIFIED IN THE LUNG
BEFORE.
WHEN THAT SIGNATURE WAS BLASTED
AGAINST ALL OTHER ORGANS IN THE
BODY ISSUES THE PROFILE
OVERLAPPED REMARKABLY WITH THAT
OF THE U TERUS, IN ADDITION THE
TUBEEROUS MUTATION IN THE LUNG
OF 1 OF THE PATIENTS WERE DEMON
TRAITED TO BE IDENTICAL
DEMONSTRATING THE SOIRS AS THE
CELL FROM THE UTERUS THAT
DESTROYS THE LUNG.
AND FOR IPF THESE ARE PUBLICLY
AVAILABLE IN THE ATLAS.
NEXT SLIDE, PLEASE.
SO JUST REVIEWING LAM FOUNDATION
ROLES AND LAM PROGRESS, LAM
FOUNDATION ORGANIZED EDUCATED
MOBILIZED PATIENTS, CONDUCTED
ANNUAL PATIENT INVESTIGATOR
CONFERENCES, THAT GAVE HOPE TO
PATIENTS AND INSPIRATION TO
SCIENTISTS, IT'S HARD TO
OVERSTATE HOW MUCH THAT KIND OF
INSPIRATION CONTRIBUTED TO THE
COMMITMENT OF OUR INVESTIGATORS.
THEY DEVELOPED THE LAM CLINIC
NETWORK TO FOCUS REFERRALS AND
NURTURE EXPERTISE AND FACILITATE
RESEARCH, DEVELOP A PEER
REVIEWED SCIENTIFIC RESEARCH
PROGRAM, THAT FORM THE BASIS FOR
TRIALS, PARTNER INDEED LARGE
GRANT INITTIAIVE ITS SUCH AS THE
NIH FOR A LUNG DEC CONSORTIUM,
PLAYED KEY ROLE IN TRIAL FUND
NOTHING THE CONDUCT OF
RANDOMIZED TRIALS INCLUDING
MILES AND MILED.
AND RESULTED IN BIOMARKER AND
EFFECTIVE TREATMENT.
IT FUNDED EARLY STUDIES
IDENTIFYING THE METASTATIC
MECHANISMS AND RECENT STUDIES
IDENTIFYING THE TERROUS OF THE
SOURCE OF THE CELL THAT DESTROYS
THE LUNG, FUNDED PRACTICAL GUIDE
LINES AND PATIENT CONFERENCES
AND ENDOWED A CHAIR FOR
SUSTAINABLE SCIENTIFIC COUNSELS
AND I WILL ADVOCACY WITH PHARMA,
FDA, NIH AND CONGRESS.
NEXT SLIDE ISSUES PLEASE.
THERE ARE MANY PEOPLE TO THANK
AND ONLY A FEW OF THEM ARE
REPRESENTED HERE, BUT CO
INVESTIGATORS AND MULTIPLE
TRIALS, LAM FOUNDATION, MILES PI
AND SITE TEAMS, OUR UNIVERSITY
AND CHILDREN'S HOSPITAL SUPPORT,
FDA FOR THEIR HELP WITH GETTING
THE APPROVAL OF THE DRUG
COMPLETED AND A LOT OF HELP FROM
PFIZER FROM THE VERY BEGINNING
PROVIDING THE DRUG THROUGH
PURSUING COMPLETE FDA APPROVAL
WITH US.
THANK YOU VERY MUCH.
>> THANK YOU DR. Mc CORMACK,
LOOK FORWARD TO TALKING TO YOU
AS WELL DURING THE PANELMENT SO
NEXT WE ARE GOING TO HAVE THE
BRIDGE TO A PANEL DISCUSSION.
AND DR. CASE WILL SPEND A FEW
MINUTES MAKING THAT BRIDGE
BEFORE WE BRING EVERYONE BACK
FOR THE DISCUSSION.
>> THANK YOU MARRAH, APPRECIATE
THAT.
I JUST WANTED TO TAKE A FEW
MINUTES AND NOT NECESSARILY
REVISIT ALL OF THE GREAT
INITIATIVES AND INFORMATION THAT
OUR OTHER PANELISTS HAVE TALKED
ABOUT BUT SORT OF ECHO A FEW
THINGS THAT HAVE SOME MICE
OVERLAP WITH THE PULMONARY
FIBROSIS FOUNDATION.
BEFORE I GET STARTED I WOULD
LIKE TO THANK THE COMMITTEE FOR
THIS OPPORTUNITY TO SPEAK WITH
EVERYONE AND TO SPEAK WITH OUR
PANELISTS TODAY.
I WANTED TO SHARE A LITTLE BIT
ABOUT THE PF FOUNDATION AND SOME
OF THE WAYS THAT ARE EXPERIENCE
JUST REFLECTS THOSE IMPORTANT
WAYS THAT PATIENT ADVOCACY
ORGANIZATIONS CAN SUPPORT
THERAPEUTIC DEVELOPMENT.
NEXT SLIDE, PLEASE.
SO THE PFF IS A PATIENT ADVOCACY
NONPROFIT ORGANIZE EGG,
DEDICATED TO ADVANCING CARE OF
PEOPLE WITH PULMONARY FIBROSIS
AND OUR MISSION IS REFLECTED IN
THE SIGNATURE PROGRAMS, I NOT GO
INTO DEPTH OF ALL THINGS WE DO
AT THE PULMONARY FIBROSIS
FOUNDATION BUT I HIGHLIGHT A FEW
OF OUR PROGRAMS.
ONE OF THOSE PARTS OF THE
MISSION ACCELERATING NEW
THERAPEUTIC DEVELOPMENT INCLUDES
PROGRAMS AND INVESTMENTS INTO
EARLY CAREER
INVESTIGATORS, THROUGH OUR
PFF SCHOLARS PROGRAM, OUR
REGISTRY WHICH I WILL TALK A
LITTLE BIT MORE ABOUT IN DEPTH
AND OUR WORK SUPPORTING CLINICAL
TRIAL EDUCATION AND RECRUITMENT.
ANOTHER PILLAR OF THAT MISSION
IS ADVANCING QUALITY OF CARE
THROUGHEUR CARE CENTER NETWORK,
IT WAS FOUNDED IN 2014 WITH JUST
A HANDFUL OFITES BUT NOW CLIN
CLUEDS MORE THAN 80 U.S. BAS
CENTERS IN THE VAST MAJORITY OF
ESTATES WE DON'T REACH ALL OF BO
EXPANSION OF A CLINICAL
ASSOCIATES PARTNER NETWORK THAT
IS MORE OUTSIDE OF LARMINGER
ACADEMIC INSTITUTIONS AND
REACHES INTO SOME OF THE SMALLER
COMMUNITY BASED PRACTICES THAT
CARE FOR SO MANY OF OUR PATIENTS
THAT DON'T COME TO LARGER
CENTERS.
AND FINALLY WE BUILD COMMUNITY
WITH OUR SUPPORT PROGRAM ANDS
EDUCATIONAL PROGRAMS, INCLUDING
OUR SERIES, WE HAVE A
LOT OF EDUCATIONAL CONTENT ON
OUR WEBSITE AND THOSE PRINTED
MATERIALS THAT ARE GOING OUT TO
SUPPORT GROUPS AND TO CLINICS.
ASK OUR BI-ANNUAL PULMONARY
FIBROSIS SUMMIT THAT INCLUDES
PATIENTS, CAREGIVERS, HEALTHCARE
PROFESSIONALS AND INDUSTRY
PARTNERS WHICH IS A REALLY
UNIQUE OPPORTUNITY FOR THOSE
PARTIES TO ALL BE TOGETHER IN AN
EDUCATION AND NETWORKING
CAPACITY.
NEXT SLIDE PLEASE.
THE PULMONARY FIBROSIS
FOUNDATION'S PATIENT REGISTRY
BEGAN PLANNING YEARS BEFORE THE
FDA APPROVAL OF THE 2 EXISTING
ANTIFIBROTIC THERAPIES, AND ALL
THE PLANNING AND MORE FUNDING
THAT BECAME AVAILABLE AFTER THE
ADVENT OF THOSE THERAPIES
LAUNCHED INUN 2016 AND RECRUITA
ITS GOAL OF 2000 SUBJEKS IN A
CENTER-BASED FASHION FROM 42
EXISTING CARE CENTER SITES AT
THAT TIME.
THE SUBJECTS INCLUDED ARE VERY
WELL CHARACTERIZED, CLINICALLY,
THELI DATA COLLECTION WENT ON FR
OVER 5 YEARS, AND INCLUDES HIGH
RESOLUTION CT IMAGING, BLOOD
SAMPLES AT BASE LINE, CEREAL
PULMONARY FUNCTION TESTS AND
PATIENT REPORTED OUTCOMES
REPORTED AS WELL.
THE REGISTRY SOUGHT DATA
THAT 5 + YEAR TIME PERIOD WE DID
SEE OF COURSE ATTRITION BASED ON
THE MORTALITY OF PULMONARY
FIBROSIS, BUT TO DATE, THE DATA
HAS BEEN INCREDIBLY VALUABLE,
IT'S BEEN USED FOR MORE THAN 50
DIFFERENT RESEARCH STUDIES, WE
HAVE OTHERS THAT ARE IN PROGRESS
AND ACADEMIC AS WELL AS INDUSTRY
PARTNERS THAT ARE STILL
INTERESTED IN UTILIZING THAT
DATA, FOR THEIR DIFFERENT
PROJECTS.
MOST OF THE STUDIES THAT HAVE
BEEN DONE TO DATE ARE CLINICAL
BUT THE BASIC AND TRANSLATIONAL
INVESTIGATIONS ARE ALSO VERY
WELL REPRESENTED.
NEXT SLIDE, PLEASE.
I WANT TO HIGHLIGHT 2 PROGRAMS
THAT HAVE UTILIZED AND BORN
FROM, THE REGISTRY DATA AND NOT
INCLUDE THE PRECISIONCI STUDY
WHICH IS THE FIRST PHARMA CO
GENOMICS STUDY IN IDIO PATHIC
PULMONARY FIBROSIS.
IT TOOK ITS INITIAL RECRUITMENT
DIRECTLY FROM THE PFF REGISTRY
REGISTRY
PARTICIPANTS.
THOSE WERE PRESCREENED FOR THE
TILE-UP GENO TYPE OF INTEREST
AND THE SITES THAT PARTICIPATED
IN THE REGISTRY WERE THEN ABLE
TO REACH OUT DIRECTLY TO THE
SUBJECTS AND RECRUIT THEM
QUICKLY INTO THE STUDY.
AND THEN ALSO THE PROLIFIC
CONSORTIUM THAT DR. NUTTER
MENTIONED EARLIER WHICH INVOLVES
16 INDUSTRY PARTNERS ISSUES THE
PULMONARY FIBROSIS FOUNDATION
AND 3 LAKES FOUNDATION TO USE
THE REG TREE TO IDENTIFY
CIRCULATING PULMONARY MARKERS
AND FIBROSIS.
NEXT SLIDE, PLEASE.
IN ADDITION TO THE SCIENTIFIC
WORK AND THE REGISTRY, AS THAT
VALUABLE TOOL, I WANT TO
HIGHLIGHT SOME OF THE WORK WE DO
IN EDUCATION AS WELL AS
RECRUITMENT FOR CLINICAL TRIALS.
WE CAN DO ALL OF THAT AND ALL
OUR PATIENTS TO PARTICIPATE IN
THOSE CLINICAL TRIALS AND AS WE
CAN SEE THEY DON'T GO ANYWHERE,
SO WE'RE VERY FORTUNATE TO HAVE
A ROBUST PIPELINE, BUT WE'RE
RECRUITING FOR A RELATIVELY
SMALL POPULATION, WITH LOTS OF
BARRIERS TO TRIAL ENROLLMENT AND
SO, WE DO HAVE A ROBUST SUITE OF
EDUCATIONAL OFFERINGS AT THE
FOUNDATION INCLUDING THOSE
SPECIFIC TO RESEARCH AND
CLINICAL TRIALS.
OUR WEBSITE HAS A CLINICAL
TRIALS EDUCATION CENTER, WHERE
PATIENTS CAN FIND INFORMATION
ABOUT CLINICAL TRIALS
THEMSELVES, WHAT'S IT LIKE TO
PARTICIPATE AND THEN ALSO
INFORMATION ABOUT SPECIFIC
CLINICAL TRIALS.
WE HAVE A PIPELINE THAT IS KEPT
UP TO DATE ON THIS SITE WHERE
THEY CAN GO AND LOOK AT WHAT IS
IN DEVELOPMENT AND FIND
INFORMATION ON STUDIES OF
INTEREST TO THEM. HAVE WRITTENAT
CAN BE USED I CLINIC, I USE
THIS REGULARLY, TO EDUCATE MY
PATIENTS ON CLINICAL TRIALS AND
PARTICIPATION AS WE'REALKING
ABOUT SCREENING AND ENROLLMENT,
AND THEN WE HAVE DIDACTIC
TEACHING OFFERINGS THROUGH OUR
WEBINARS AND DURING OUR
IN-PERSON EDUCATION AT THE
BI-ANNUAL SUMMIT.
NEXT SLIDE, PLEASE.
AND THEN FINALLY I'LL MENTION
OUR CLINICAL TRIAL FINDER WHICH
IS IN PARTNERSHIP WITH THE CARE
BOX PLATFORM, IT ALLOWS PATIENTS
TO GO IN AND CREATE A PROFILE
THEY CAN ENTER THENT OWN
THEY CAN ACTUALLY MATCH TOL THEL
STUDIES WITHIN A CERTAIN RADIUS,
FOR WHICH THEY MIGHT BE
ELIGIBLE, AND THEN IT PROVIDES
SUPPORT TO INTERESTED PATIENTS
VIA E-MAIL AND TELEPHONES.
THEY CAN REACH A LIVE PERSON,
MOST OF THE PEOPLE WHO REACH OUT
TO THE PLATFORM HAVE MULTIPLE
CONTACTS FOR CLARIFYING AND WITH
HELP FOR REACHING OUT TO STUDY
SITES IF IT'S NEEDED.
NEXT SLIDE,E.
SO BEFORE WE GET TO OUR PANEL, I
WANT TO JUST LASTLY HIGHLIGHT
THE IMPORTANCE OF PATIENT
PARTICIPATION AND CAREGIVER
SUPPORT AT ALL POINTS IN THAT
CLINICAL TRIAL PROCESS, WE
UNDERSTAND THAT AGAIN, THERE ARE
LOTS OF BARRIERS TO CLINICAL
TRIAL PARTICIPATION FOR PEOPLE,
BE THEY DISTANCE, KNOWLEDGE,
ACCESS, INCLUSION EXCLUSION
CRITERIA, A SUPPORT PERSON TO BE
WITH THEM DURING THEIR VISITS
AND SO ON, AND SO, WE RECOGNIZE
THAT INPUTS FROM THOSE PATIENTS
OR CAREGIVERS AS TRIALS ARE
DEVELOPED AND ALONG THE WAY IS
REALLY IMPORTANT AND VITAL AND I
THINK THIS IS REFLECTED NICELY
IN DR. Mc CORMAC'S CONFERENCE,
WHAT'S IMPORTANT TO THEM IN
GETTING THAT FEEDBACK WE'RE
PLANNING.
AND I THINKAN THA IS MY LAST
SLIDE.
I THINK IT'S TIME WE CAN GO TO
OUR PANEL.
AS I REMINDER YOU CAN POST YOUR
QUESTIONS IN THE Q&A TOOL.
ON THE SCREEN.
AND WE WILL BRING OUR PANELISTS
BACK.
>> JUST GIVE US A SECOND TO
BRING YOU INTO PANELISTS MODE.
DR. NETWORK ICK E-- NICKERSON,
CAN YOU TURN ON YOUR CAMERA AND
JOIN US, ALL RIGHT, I THINK WE
HAVE EVERYBODY.
>> GREAT.
>> WHILE WE'RE WAITING FOR
QUESTIONS TO COME INTO THE TOOL,
YOU KNOW I THINK THERE WAS A
COMMON THEME OF REALLY HAVING,
YOU KNOW A LOT OF DIFFERENT
BARRIERS TO COMPLETING CLINICAL
TRIALS, ENROLLING IN CLINICAL
TRIALS, AND I JUST WANTED TO
TOUCH ON THAT.
I THINK WITH A COUPLE OF
QUESTIONS AND I WILL JUST START
WITH 1 UNTIL WE CAN GELT
QUESTIONS COMING IN, BUT I WILL
FEED ON THIS THEME IF NEEDED.
SO YOU KNOW WITH THE ERA OF
COVID, A KNOW A LOT OF CLINICAL
STUDIES HAD TO PAUSE BECAUSE WE
COULDN'T CONDUCT RESEARCH VISITS
RELATED TO OBSERVATIONAL STUDIES
AND SOMETIMES WE WERE HAVING
DIFFICULTIES WITH CLINICAL
TRIALS AND THERE WAS A MOVEMENT,
I KNOW BY A LOT OF GROUPS,
SPECIALLY IN THE PULMONARY AND
SLEEP RESEARCH COMMUNITY TO MOVE
INTO YOU KNOW REMOTE ACCESS TO
PATIENTS AND THEN IN TURN, THINK
ABOUT NOVEL WAYS TO CONDUCT
CLINICAL TRIALS AND I THINK THAT
THIS IS AN IMPORTANT THING THAT
MAYBE YOU ALL COULD DISCUSS
BECAUSE IT RELATES BACK TO WHAT
END POINTS THE FDA MIGHT ACCEPT.
AS, YOU KNOW TRIALS ARE GOING
INTO THE FUTURE AND THE IDEA OF
EQUITABLE ACCESS, IN REACHING
OUTSIDE OF THOSE HIGH RESOURCE
ACADEMIC RESEARCH CENTERS, SO, I
THINK THAT ANYBODY CAN START
WITH THAT QUESTION, BUT I THINK
THAT THAT'S AN IMPORTANT THING
THAT WE SHOULD TALK ABOUT IN
REALLY THINKING ABOUT THE
BARRIERS AND FACILITATORS TO
ACCESS AND ENROLLMENT FOR THESE
CLINICAL TRIALS.
>> I CAN START.
HOPEFULLY THAT WILL -- MY
COMMENTS WILL HELP PROMPT SOME
ADDITIONAL DISCUSSION BUT THIS
IS AN ONGOING DISCUSSION AMONG
OUR -- WE HAVE A WORKING GROUP
THROUGH OUR CARE CENTER NETWORK
FOR RURAL HEALTH ACCESS AND SO
WE UNDERSTAND THAT NOT ONLY
ACCESS TO CLINICAL CARE BUT
CLINICAL TRIAL VERY LIMITED FOR
PATIENTS IN THE RURAL SPACE.
CERTAINLY THERE ARE BARRIERS TO
ACCESS AND MORE SUBURBAN AND
URBAN AREAS AS WELL, BUT
DISTANCE, TRAVEL, TIME SPENT,
THINGS LIKE THAT, PARTICULARLY
FOR PATIENTS WHO NEED A
CAREGIVER, WHO ARE ON OXYGEN,
THEY HAVE LIMITATIONS IN HOW
LONG THEY CAN BE AWAY FROM HOME.
I SEE HEADS NODDING, ARE
BARRIERS AND I THINK WE HAVE --
THERE ARE IDENTIFIED SOME
SUCCESSFUL EXAMPLES, MORE PROOF
OF CONCEPT, I THINK IN
DECENTRALIZED TRIALS IN
PULMONARY FIBROSIS, WHERE THE
PATIENTS CAN ENROLL VIRTUALLY
AND THEN DO STUDY ASSESSMENTS
LOCALLY AND HAVE THEM SENT TO A
CENTRAL MONITOR.
THERE'S RECENTLY A STUDY OF
NANTIDINIB IN MY O
[INDISCERNIBLE] ILD, THE
UNIVERSITY OF COLORADO'S APPLE
STUDY DID A LOT OF REMOTE DATA
COLLECTION FOR THEIR FAMILIAL
COHORT THERE, SO I THINK THAT
IT'S UNDERSTANDING WHAT THOSE
CHALLENGES ARE BECAUSE FOR THE
MORE REGISTRATIONAL STUDIES THE
DATA HAS TO BE CLEAN AND I THINK
THE CHALLENGES WITH THOSE LOCAL
COLLECTIONS OF DATA WAS THE
DIFFERENCES IN PERHAPS CT SCANS
OR PFT MEASURE AMS AND THINGS
LIKE THAT, ACTUAL ACTUALLY COM,
IT WASN'T THE PATIENT'S
PARTICIPATION, THEY WERE WILLING
TO DO THOSE THINGS BUT THE
FIDELITY OF THE DATA THEY WERE
GETTING OUT OF THAT.
I WOULD LOVE TO HEAR THE
EXPERIENCE IN OTHER AREAS ON
THAT.
>> WE'VE DONE A LITTLE BIT WITH
THAT, AND PART OF THE ISSUE THAT
WE'VE RUN INTO WITH REMOTE
TRIALS IS VALIDATION OF THE
TOOLS THAT ARE -- ARK
ASSESSESMENT TOOLS THAT ARE
BEING USED SO FOR INSTANCE,
COUGH CONING AT NIGHT, IT SOUNDS
GREAT BUT IF YOU DON'T SLEEP BY
YOURSELF IN A QUIET ROOM, IT'S
NOT RELIABLE, IF YOUR DOG
COUGHS, IT'S NOT RELIABLE, SO
WE'RE WORKING WITH SOME AGENCIES
TO SEE IF THIS PASSIVE DATA CAN
BE VALIDATED FOR COLLECTION BUT
I THINK WELL'S SOME SKEPTICISM
UNTIL WE CAN GET VALIDATION OF
SPIRITUAL STRUGGLES
O--METABOLIZEDETRY, REMOTE
SPIROMETRY.
>> I WOULD ADD THERE'S 2 ANGLES
TO THE QUESTION, RIGHT WHICH IS
1 THE USE OF -- THE VALIDATION
OF TECHNOLOGY FOR YOU KNOW
THERE'S A HIGH DEGREE OF
SENSITIVITY AND SPECIFICITY AND
IN PRECISION NEEDED FOR CLINICAL
TRIAL ANDS THEN THERE'S THE
QUESTION OF, YOU KNOW WHAT'S
USEFUL FOR PATIENTS, TOO, AND I
KNOW THE CF FOUNDATION
SPONSORED, I RECEIVED A PORTABLE
SPIROMETRY DEVICE DURING EARLY
COVID AND FORTUNATELY, COVID
ALSO COINCIDED WITH TRIKAFTA'S
APPROVAL SO FOR MANY OF US IT
WAS A VERY DIFFERENT TIME BUT
THE POINT I THINK IS IN RECENT
YEARS, I THINK THERE'S BEEN SOME
INVESTIGATION INTO THE
VALIDATION AND COMPARISON OF A
LOT OF THESE PORTABLE SPIROMETRY
DEVICES BUT AT THE END OF THE
DAY WHAT'S USEFUL TO PATIENTS A
LOT OF TIME SYSTEM NOT
NECESSARILY THE ABSOLUTE VALUE
BUT DAY-TO-DAY CHANGES AND
MEASURING AND SEEING AND REALLY
SEEING THE PATTERN AND THE
TREND.
AND SO, I WOULD LIKE TO THINK,
YOU KNOW COVID WAS HORRIBLE FOR
A MILLION DIFFERENT REASONS BUT
I THINK THAT IT ALSO OPENED US
TO YOU KNOW THE POINTS THAT
MICHELLE AND AMY HAVE MADE THAT
IT WAS AN OPPORTUNITY TO
EXPERIMENT AND SEE HOW WE CAN
ADDRESS THE STILL MASSIVE
DISPARAGING DISEASES IN
COMPLIEWNTS IMEGGABLE ESPECIALLY
IN RURAL AND MINORITIZED GROUPS.
SO IT'S IMPORTANT TO USE
OPPORTUNITIES LIKE THAT TO
INNOVATE AND BE A BIT MORE
WILLING TO BE DYNAMIC WITH, YOU
KNOW THE SYSTEM.
>> I WOULD -- I COMPLETELY AGREE
THAT THE ACCURACY OF PULMONARY
FUNCTION TESTS IS PARAMOUNT IN
SOME OF THESE TRIALS AND THAT
THERE ARE END POINTS THAT ARE
MORE IMPORTANT THAN OTHERS IN
THIS 2 YEAR LONG MILD TRIAL.
WE WANT TO BE SURE THAT PATIENTS
HAVE THEIR PULMONARY FUNCTION
TESTS AT OUR LABORATORY AND
WE'VE RELAXED THE NEED TO HAVE
PULMONARY FUNCTION TESTS YOU
KNOW AT OUR LABORATORY FOR
REMOTE VISITS THAT OCCUR IN
BETWEEN.
AND I THINK THAT'S GOING TO
BECOME A PART OF OUR TRIALS
GOING FORWARD, I THINK THERE'S
DEFINITELY A PLACE FOR REMOTE
VISITS.
WE WILL PROBABLY DO A HYBRID
MODEL WHERE WE HAVE BOTH REMOTE
AND IN-PERSON VISITS AT THE SITE
SO WE HAVE AT LEAST SOME
MEASURES THAT ARE KNOWN TO BE
DONE AND CALIBRATED, YOU KNOW
HIGH QUALITY ATS, WELL DRIVEN 8
PULMONARY FUNCTION LABS AND IN
THE CONTEXT OF MILD, DOING A
PARALLEL HOME SPIROMETRY STUDY
LIKE TRE WAS TALKING ABOUT AND
WE'VE SEEN VERY GOOD TREND
AGREEMENT WITH WHAT'S FOUND WITH
HOME SPIROMETRY AND OFFICE
SPIROMETRY.
THE ABSOLUTE VALUES ARE NOT
IDENTICAL BUT THE TRENDS ARE
OVERLAPPING AND I THINK THAT CAN
BECOME AN END POINT IN THE
FUTURE FOR SOME STUDIES.
>> AND STUDY SELECTION WOULD BE
IMPORTANT TOO BECAUSE SOME
STUDIES MAY BE MORE AMENABLE TO
REMOTE PARTICIPATION AND EVEN IF
WE COULD DO AS MUCH REMOTELY AS
POSSIBLE, THAT STILL WOULD LIMIT
THE BURDEN ON PATIENTS TO DO
IN-PERSON VISITS.
>> YEAH, I THINK THOSE ARE ALL
GOOD POINTS AS WAYS FOR US TO
SORT OF TRY TO REDUCE THE
BARRIERS AND THEN OF COURSE, THE
LIMITATIONS ACROSS RARE DISEASES
IS ACCESS TO NUMBERS OF
PARTICIPANTS AND THE MORE WAYS
THAT THE STUDIES CAN BE DESIGNED
TO INCREASE ACCESS WOULD MAKE
THEM MORE SUCCESSFUL AS WELL.
>> WE DO HAVE 1 QUESTION IN THE
Q&A TOOL AND I INVITE OTHER
MEMBERS OF THE AUDIENCE TO POSE
QUESTIONS DURING THE DISCUSSION.
SO THIS 1 IS CENTER DR. MOFFIT,
IT SAYS WE'VE BEEN HEARING THAT
PATIENTS ARE EXCITED ABOUT
INNOVATIVE THERAPY BUT ONLY ONCE
APPROVED.
THEY'RE RELUCTANT TO PARTICIPATE
IN CLINICAL TRIALS GIVEN THE
UNCERTAINTY OF NOVEL THERAPIES
AND WHAT ARE THINGS THAT
INDUSTRY CAN DO TO BREAK DOWN
THESE BARRIER ANDS COMMUNICATE
MORE EFFECTIVELY TO PATIENTS
ABOUT THESE OPPORTUNITIES.
AND BEFORE WE GO THERE, I WILL
ADD TO THAT, IN REALLY THINKING
ABOUT COMPETITION BETWEEN MOFLE
THERAPIES AND IN THE GENE
THERAPY SPACE, YOU KNOW, THIS
MAY BE A PRIME ISSUE, AT THIS
TIME, BUT REALLY THINKING ABOUT
THE OTHER ALTERNATIVE
INTERVENTIONS THAT MAY COME IN
THE NEXT 5 YEARS, HOW WILL
INDIVIDUALS NEED TO BE EDUCATED
ABOUT THESE OPPORTUNITIES TO
HELP MAKE THESE CHOICES.
AND MAYBE, TRE, I WILL PICK ON
YOU FIRST TO ANSWER THIS
QUESTION.
>> YEAH, I WILL -- YEAH, I MEAN
I THINK IT'S AN INCREDIBLY
IMPORTANT AND SENSITIVE TOPIC
RIGHT NOW AND I THINK IT'S -- 1
OF THE -- 1 OF MY FAVORITE
CLASSES IS IN MY UNDERGRAD WAS
LEARNING ABOUT THE SORTING
SIGNALS OF SEE SAW OF PATIENT
AUTONOMY AND PHYSICIAN
PATERNALISM AND I THINK THAT'S
VERY MUCH WHAT WE'RE TALKING
ABOUT HERE, ESPECIALLY WITH
NOVEL INNOVATIVE THERAPIES, IN
THE GENE THERAPY SPACE
ESPECIALLY WHEN DISCUSSING
VACCINES, I THINK THERE'S A LOT
OF CONFUSION ABOUT A LOT OF
THINGS AND ALSO ACKNOWLEDGE THAT
I THINK WE HAVE AN INFORMATION
ENVIRONMENT THAT POSES A LOT OF
CHALLENGES FOR PEOPLE AND
CONSUMERS AND I OFTEN THINK IT'S
KIND OF INTERESTING THAT I'M A
PATIENT IN A LOT OF WAYS BUT I'M
ALSO JUST A PERSON WHO YOU KNOW,
WE ALL COULD BE A PATIENT AT ANY
GIVEN CIRCUMSTANCE, RIGHT, WE'RE
ALL A PATIENT WHEN WE GET URGENT
CARE AND 1 THING THAT'S
IMPORTANT IS THAT WE EMPHASIZE
THE NEED FOR CLINICIANS TO TALK
TO PATIENTS LIKE THEIR PEOPLE
AND FEEL CONFIDENT THAT YOU CAN
TALK TO HUMANS AND EMPOWER THEM
IN A WAY THAT DOESN'T BRIDGE TOO
CLOSE TO PATERNALISM WHILE ALSO
RECOGNIZING THAT IT'S REALLY
IMPORTANT TO SPEAK IN A HEALTH
LITERAL MANNER, THAT'S SOMETHING
WE TALKING A LOT ABOUT AT THE
FNIH AND MAKING SURE WE'RE
COMMUNICATING THESE DEEPLY
DIFFICULT -- SOME OF THE
PROJECTS WE HAVE ARE DIFFICULT
TO CONVEY TO THE CLINICIANS IN
THE FIELD SO LET ALONE THE
PHYSICIANS IN THE FIELD.
SO THAT'S WHERE IT'S REALLY
INCUMBENT ON FOLKS WHO ARE ISHT
ACTING WITH PATIENTS A LOT TO
CONTINUE NURTURING THAT SKILL OF
HEALTH LITERATURE COMMUNICATIONS
IN A WAY THAT ENABLES PATIENTS
TO UNDERSTAND WITHOUT FEELING
LIKE PEOPLE ARE BEING DICTATED
TOO.
I ALMOST MENTIONED THIS DURING
MY TALK BUT I HAD TO CUT IT FOR
TIME BUT THERE'S BEEN THE TALK
ABOUT THE TERM IN THE PAST USED
TO BE COMPLIANCE WITH PEOPLE
TAKING MEDICATIONS AND I THINK
WE'VE SORT OF SHIFTED GENERALLY
CLOSER TO ADHERENCE AND I THINK
WE TRY TO STRAY AWAY FROM ANY OF
THIS TERMINOLOGY IN GENERAL AND
COMPLIANCE SUGGESTERSA A POWER
DYNAMIC BETWEEN THE PATIENT AND
HELT CARE SYSTEM AND I THINK
THAT DOESN'T REALLY UNDERSTAND
HOW MUSEUM MANS BEHAVE AND I
THINK WHEN YOU TURN AND START TO
USE THE WORD COMPLIANCE, YOU
START TO SHIFT, SHIFT WHAT
ACTUALLY MOTIVATES HUMANS AND I
THINK IN THE SAME WAY,
COMMUNICATING ABOUT NOVEL
THERAPIES IS REALLY ABOUT
UNDERSTANDING THAT THERE HAS TO
BE AGENCY INVOLVED WHEN PATIENTS
ARE TRYING TO CONSIDER A
CLINICAL TRIAL AND ALSO 1 OTHER
POINT I WILL MAKE IS THAT IT'S
GOT TO BE FRAMED IN THE CONTEXT
OF MULTIPLE INTERACTIONS, RIGHT?
YOU'RE NOT REALLY ENROLLING A
PATIENT, THE DAY YOU ASK THEM TO
ENROLL IN A CLINICAL TRIAL, YOU
ARE REALLY ENROLLING THEM IN THE
WEEKS TO MONTHS TO YEARS DURING
THAT TRUST BUILDING FOR FUTURE
CLINICAL TRIALS, SO EVERY
INTERACTION IS AN OPPORTUNITY TO
EDUCATE AND INFORM FOLKS.
>> AND I THINK THAT ADD TO THAT,
YOU KNOW, I THINK TO JEFF'S
POINT IS HOW CAN THE -- INDUSTRY
ALSO BE IN PARTNERS IN THAT, I
THINK YOU ALLUDED TO THAT, IN
THE BARRIERS FOR TRANSLATING
HEALTH INFORMATION IN SOME OF
THESE NOVEL THERAPYS EVEN TO THE
CLINICIAN THAT'S GOING TO IN
TURN HAVE TO TRANSLATE IT BACK
TO THEIR PATIENT AND I THINK
THAT THAT IS A ROLE THAT SOME OF
THE ADVOCACY GROUPS COULD ALSO
HELP SUPPORT SO MAYBE WE CAN
HEAR FROM THEIR EXPERIENCE AS
WELL.
>> I THINK THERE ALSO REALLY
NEEDS TO BE CLARITY ABOUT THESE
NOVEL THERAPIES.
I KNOW THAT IN OUR GROUP, WE'RE
TALKING ABOUT MRNA THERAPY AND
IT IS UNCLEAR EVEN AT THIS
POINT, IF YOU PARTICIPATE IN
MRNA THERAPY FOR YOUR GENE,
RIGHT NOW, AND IT DIDN'T WORK,
DOES THAT MEAN YOU'RE GOING TO
BE PRECLUDED FROM THE THERAPIES
COMING UP IN 5 YEARS AND
PATIENTS ARE VERY WORRIED.
IT MAKES THEM WAIT, THEY WANT TO
WAIT AND SEE IF SOMETHING IS
GOING TO HELP BEFORE THEY KIND
OF BLOWN THEIR SHOT.
SO I THINK INFORMING PATIENTS,
INFORMED CONSENT.
MAKING SURE WE ALL UNDERSTAND
IT.
I DON'T EVEN KNOW.
I'VE HEARD 3 DIFFERENT PROPOSALS
IF ARE THIS, 18 MONTHS, 2 YEARS
AND 15 YEARS FOR WHEN YOU MIGHT
BE ABLE TO PARTICIPATE IN
ANOTHER TRIAL.
WE NEED MORE CLARITY ON WHAT IS
REALLY THE CONSEQUENCE S OF IT.
>> FOR LAM AND PULMONARY
FIBROSIS WE NOW HAVE FDA
APPROVED DRUGS AND IT'S
UNETHICAL TO HAVE PATIENTS
PARTICIPATE IN AN EXPERIMENT IF
YOU HAVE A PROVEN THERAPY TO
OFFER THEM AND IN THOSE DECS WE
OFTEN HAVE TO WAIT UNTIL
PATIENTS FAIL THE APPROVED
THERAPIES, FOR IPF WE HAVE 3
DRUGS WE CAN CONSIDER AND AT
THAT POINT, YOU KNOW THEY'RE NOT
AS -- IT'S NOT THE SAME
CANDIDATE AT THE END OF 2 FAILED
THERAPIES OR 3 FAILED THERAPIES
AND THE TRIAL RESULTS WITH BE
BIASED BY THAT.
SO I THINK NOX FAMILY
ACTIVATORLE THERAPIES IN SOME OF
THE DOMAINS THAT WE PRACTICE IN
AREN'T ALL THAT APPEALS TO OUR
PATIENTS BUT YEAH.
>> I WAS ACTUALLY GOING TO
COMMENT ON SOMETHING THAT TRE
SAID AS WELL AS NOW WHAT
DR. Mc CORMACK AS BROUGHT UP
BUT I WILL SAY THE LATTER FIRST,
I THINK THERE'S A DIFFERENCE
BETWEEN PATIENTS WHO GET THEIR
CARE AT CARE CENTERS, RIGHT?
AND THOSE WHO GET THEIR CARE IN
A MORE COMMUNITY-BASED PLACE,
RIGHT?
THERE ARE LOTS OF BARRIERS TO
GETTING INTO THOSE CARE CENTERS
TO START WITH, WAIT TIMES,
NAVIGATING LARGER SYSTEMS, THE
DISTANCE AND AND STUFF LIKE THAT
SO IT HELPS FOR SOME POPULATIONS
IN SOME WAYS DRIIVE TO BE THERE
AND I THINK GETTING BACK TO --
THAT MAY BE THE CHOIR THAT WE'RE
ALREADY TALKING TOO MANY TIMES
IN THOSE CLINICS.
BUT TAKING A STEP BACK AND
THINKING ABOUT HOW TREY CAN
PARTNER WITH THOSE EDUCATIONAL
OPPORTUNITIES, WE KNOW THAT 1 OF
THE -- 1 OF THE MOST IMPACTFUL
THINGS IN TERMS OF ENROLLING IN
A CLINICAL TRIAL FOR A PATIENT
IS HAVING A TRUSTED PHYSICIAN
RECOMMEND THAT FOR THEM.
AND YOU KNOW WHAT I FIND NOW, IN
THE LAST 10 YEARS, IS THAT
REFERRALS FOR PATIENTS WITH IPF
TO CLINICAL TRIALS, HAVE REALLY
FALLEN OFF.
THEY'RE DRIVING THEMSELVES TO
CLINICAL TRIAL ENROLLMENT AS
OPPOSE TO BEING RECOMMENDED BY
THEIR PRIMARY PULL
MONITORROLOGYIST, SO THERE ARE
LOTS OF IN-ROADS TO THE
HEALTHCARE PROFESSIONALS THAT
ARE IN THE COMMUNITY AND
EMPHASIZING CLINICAL TRIALS AS A
CARE OPTION AS PART OF THEIR
CLINICAL CARE FOR PATIENT WHO IS
ARE ELIGIBLE FOR THOSE CLINICAL
TRIALS.
IT'S SO IMPORTANT.
IT'S NOT AN EITHER OR, IT SHOULD
BE GOING ALONGSIDE.
YOU KNOW MANY IPF SITES AT THIS
POINT FOR AT LEAST SOME PORTION
OF PARTICIPANTS ALLOW BACKGROUND
THERAPY, MAKE IT A LITTLE MORE
CHALLENGING TO REACH THOSE END
POINTS, BUT, THAT SHOULD NOT
EXCLUDE PATIENT -- IT SHOULDN'T
BE THOUGHT OF AS I FAILED
EVERYTHING, NOW, WHAT'S THE
CLINICAL TRIAL OPTION.
I'VE PROGRESSED TO END OF LIFE,
NOW, WHAT'S MY CLINICAL TRIAL
OPTION, IT SHOULD BE AN EARLY
ON, YOU KNOW, THAT CAN GO
ALONGSIDE WITH ALL OF THE OTHER
APPROPRIATE LYNNICAL CARE THAT
PEOPLE ARE GETTING AND THEN I
WILL GO BACK TO WHAT TRE WAS
SAYING, I THINK SHARED DECISION
MAKING AS OPPOSE TO SORT OF A
MORE PATERNALISTIC WAY OF
LOOKING AT THINGS.
IT'S NOT -- IT'S NOT INFORMING
AND THEN SAYING THIS IS WHAT YOU
DO.
THIS IS A SHARED DECISION, THIS
IS PRESENTING OPTIONS AND
ASSESSING VALUES AND KNOWING
WHERE PEOPLE NEED TO BE AND
WHAT'S IMPORTANT FOR THEM AND I
THINK THAT APPROACH IS MUCH MORE
LIKELY TO YIELD SOMEBODY WHO HAS
NOR TRUST BOTH IN THE MEDICAL
SYSTEM AS WELL AS IN A CLINICAL
TRIAL OPPORTUNITY.
>> I WILL CONTINUE TO ENCOURAGE
PEOPLE TO POST QUESTIONS IN THE
Q&A TOOL AND MAYBE I WILL ASK
ANOTHER QUESTION.
YOU KNOW A LOT OF THINGS WE
TALKED ABOUT ARE THE LIMITATIONS
OF EFFECTIVE BIOMARKERS FOR SOME
OF THESE RARE DECS AND
CONVINCING THE FDA, WHAT IS A
RELEVANT BIOMARKER AND THAT CAN
BE A MYRIAD OF THINGS YOU
DISCUSSED, IT COULD BE BLOOD
BASED, IMAGE BASED BUT THEN ALSO
THINKING ABOUT PATIENT REPORTED
OUTCOMES AND SO, I WONDERED IF
YOU COULD TALK ABOUT A LITTLE
BIT OF THOSE MODALITIES FOR SOME
OF THE RARE DISEASES AND HOW
THEY MAY BE MOVING CLOSER TO
ACCEPTANCE BY NOT ONLY THE
RESEARCH COMMUNITY AS VALIDATED
BY BIOMARKERS BUT POTENTIALLY
FOR THE FDA AND IN PARTICULAR
HOW AN INDIVIDUAL MAY FEEL AND
THEY PERCEIVE THEIR HEALTH
STATUS AFTER AN INTERVENTION MAY
ALSO BE A REALLY GOOD MEANINGFUL
OUTCOME AND IT'S NOT SOMETHING
THAT WE TOUCHED A LOT DURING THE
SESSION, SO IF WE COULD TALK
ABOUT THAT A LITTLE BIT MORE, I
WOULD APPRECIATE IT.
>> I'LL GO AHEAD AND JUST SAY
THAT I THINK, YOU KNOW, I WAS
WATCHING WITH BAITED BREATH WHEN
THE FDA STARTED RELEASING THE
PATIENT FOCUSED DRUG DEVELOPMENT
GUIDANCE A LOT FOR THIS REASON A
LOT AND THE TYPICAL FEELS
FUNCTION AND SURVIVES PARADIGM,
IT'S HARD PARSING OUT HOW 1
FEEL'S IS ALSO, I DIDN'T TALK
ABOUT THIS DURING MY TALK BUT
I'VE EXPERIENCED AND LIVED WITH
ANXIETY AND DEPRESSION FOR QUITE
SOMETIME AND YOU CAN'T REALLY
SEPARATE WHEN YOU'RE DEALING
WITH CHRONIC CONDITIONS YOU
CANNOT SEPARATE ALL THESE
EXTERNALITIES FROM HOW SOMEBODY
FEELS AND I THINK IT'S REALLY
IMPORTANT THAT THE FIELD
PRIORITIZES VALIDATION AND
UNDERSTANDING OF PATIENT
REPORTED OUTCOMES AND I THINK OF
THE FDA A LOT AS A HELP ME HELP
YOU SITUATION WHERE I THINK THE
FDA IS EAGER TO MOVE THINGS IN
AN INNOVATIVE DIRECTION BUT I
THINK IT'S REALLY INCUMBENT ON
THE FIELD TO COME TOGETHER TO
SORT OF DRIVE AND GENERATE THAT
DATA TO DEMONSTRATE AND YOU KNOW
THERE'S A WHOLE FIELD OF
INVESTIGATORRING THE PLACEBO
EFFECT AND UNDERSTANDING,
PARSING OUT WHAT'S HAPPENING
WHEN PEOPLE REPORT IMPROVEMENTS
WITH THE PLACEBO, WITH PLACEBO,
BUT ULTIMATELY, IT'S -- I OFTEN
-- WHEN I TALK TO PATIENTS ABOUT
THIS, I TALK ABOUT PATIENT
REPORTED OUT COMES AS WE DON'T
WANT -- IT'S NOT GOOD FOR
PATIENT COMMUNITIES IN MY VIEW
TO COME TO A ARE AND SAY THIS
TREATMENT'S NOT WORKING AND THEN
EXPECT THAT RELATIONSHIP TO JUST
BE THAT THE DOCTOR SAYS, OKAY
THAT'S DRUG'S NOT WORKING NOT
SAYING THAT THE PATIENT SHOULD
NOT HAVE THEIR EXPERIENCE
VALIDATED BUT I THINK THE POWER
OF PATIENT REPORTED OUTCOMES IS
A METHOD LOGICAL APPROACH TO,A
ASSESSES HOW PEOPLE ARE FEELING
IN A WAY THAT GETS INTO MAYBE
THE MORE INEFFABLE PARTS OF
MEDICATION, I DON'T KNOW IF THAT
ANSWERS YOUR QUESTION MARRAH,
BUT THAT'S MY PERSPECTIVE ON
PATIENT REPORTED OUT COMES.
THEY'RE LIKE ANYTHING ELSE A
TOOL THAT CAN BE POWERFUL TO
STRENGTHEN THE CASE OF
THERAPEUTICS.
>> YEAH AND I THINK 1 CHALLENGE
WE HAVE TO UNDERSTANDING EARLIER
DISEASE AND DEVELOPING
BIOMARKERS IS THAT IF WE JUST
START FOLLOWING ANYBODY WHO HAS
SOMETHING ON A SCAN, YOU KNOW 10
OR 20% MIGHT GO ON SO HAVE YOU A
LOT OF NOISE.
SO CAN WE FIGURE OUT WHO THOSE
PEOPLE ARE?
SO AGAIN, WE'RE LOOKING BACK,
AND WE'RE TRYING TO ANALYZE THE
HRCT SCANS FROM WHAT I CALL
PRESEIZE, WE DON'T HAVE GOOD
LANGUAGE TO DESCRIBE THIS, CAN
WE SEE SOMETHING THERE WITH A
NEW TECHNOLOGY, RIGHT?
SO THEY'VE BEEN LOOKED AT 10
YEARS AGO 12 YEARS AGO COULD WE
SEE ANYTHING THAT WE COULD THEN
ENRICH A POPULATION TO FOLLOW OR
HOPEFULLY FIND OR FOLLOW A
BIOMARKER SO YOU COULD INCREASE
YOUR RISK SCORE.
SO THERE'S A LOT OF PLACES WE'VE
DONE WORK WITH THE LAHEY CLINIC
WHERE IF YOU HAVE AN ILA YOU GO
TO A LUNG HEALTH CLINIC BUT
AGAIN THAT COULD SCARE PEOPLE,
YOU HAVE AN ILA YOU HAVE TO GO
TO THE LUNG CLINIC SO WHO SHOULD
GO AND WHO SHOULDN'T?
SO CAN WE GET A BIOMARKER RISK
SCORE, WHERE WE CAN PREYECT MORE
WHO WILL PROGRESS AND GET THEM
IN EARLIER AND IT'S ONLY GOING
TO BE DONE IF WE CAN FOLLOW OVER
TIME AND TOO, IF WE CAN GET THEM
EARLIER, THAT WOULD BE GREAT BUT
THEN HOW DO WE DO A CLINICAL
TRIAL.
WE NEED VALIDATED BIOMARKERS SO
SOMEHOW WE HAVE TO START DOING
THAT NOW BECAUSE IT'S SUCH A
LONG PROCESS, SO WHAT CAN
INDUSTRY BE PUTTING INTO THEIR
CLINICAL TRIALS OR LOOKING AT IN
AITITION TO FVC IN EAPGZ FOR THE
FUTURE.
I MEAN WE HAVE TO START NOW.
SMRKS SO WE'VE HAD A LITTLE
TRIEWBL AND THIS GOES TO
PREDISEASE STATE.
FOR SOME OF THESE DECS THERE'S
NO PREDEC STATE TO PROVIDE A
BASE LINE.
SO WE HAVE A VALIDATED TOOL, A
HEALTHCARA QUALITY OF LIFE FOR
PATIENTS BUT IT'S NOT BEEN
EFFECTIVE BUT WHEN YOU'RE
SYMPTOMATIC EVERY SINGLE DAY AND
YOU'RE ASKING PEOPLE HOW THEY
FEEL FOR A 1 OR 2 WEEK PERIOD,
IT HASN'T BEEN PARTICULARLY
ENLIGHTENING.
THE ISSUE WE HAVE IS FINDING
GOOD VALIDATED PATIENT REPORTED
OUTCOMES.
IT'S NOT THAT WE'RE NOT
INTERESTED IN DOING IT, WE
HAVEN'T FOUND THE RIGHT
MECHANISM.
>> AND I'LL JUST SAY A FEW WORDS
ABOUT THIS, VEG FD IS A POWERFUL
BIOMARKER.
IT'S A POWERFUL BIOMARKER.
IF IT'S POSITIVE THE SPECIFICITY
IS 98%.
EVEN IF IT'S WITHIN, YOU KNOW
20% OF POSITIVE, IT'S STILL
BETTER THAN 90% SPECIFIC.
IT'S NOT VERY SENSITIVE, THIS IS
ABOUT HALF OF PATIENTS.
AS A PROGNOSTIC BIOMARKER, IT'S
GOT SOME VALUE, BUT NO VALUE AS
AN END POINT AT ALL, SO THERE
ISN'T -- DESPITE A LOT OF
RESEARCH, THERE ISN'T A
BIOMARKER I COULD APPROACH THE
FDA ABOUT THAT WOULD BE A
SUITABLE END POINT AND I WOULD
SUGGEST THAT'S TRUE FOR IPP AS
WELL, IT ISN'T AS IF WE'RE GOING
TO THE FDA WITH PLAUSIBLE
CANDIDATES AND BEING REJECTED
FOR, YOU KNOW UNJUST REASONS,
IT'S THAT WE HAVEN'T CONVINCED
OURSELVES THAT WE ARE A
BIOMARKER THAT IS A SUITABLE END
POINT.
THAT'S MY PERSPECTIVE ON THINGS.
SO, I THINK TRE'S EXACTLY RIGHT,
THEY WANT TO BE HELPFUL, WE HAVE
TO BRING THEM SOMETHING THAT'S
ACTUALLY APPROVABLE.
>> I THINK SOME OF THE
CANDIDATES COULD BE FIGURING OUT
CT SCANS, RIGHT BECAUSE THEY ARE
TIED TO DISEASE BUT YET THEY'RE
NOT PREDICTIVE OR IT HASPT BEEN
VALIDATED AND I THINK THOSE ARE
BEING DONE IN TRIALS ALL THE
TIME SO FIGURE THAT OUT AND THEN
THERE MIGHT BE SOME COLLEGE AND
BI-PRODUCTS THAT BE LOOKED AT.
SO THERE ARE SOME THINGS THAT
COULD BE LOOKED AT AND I KNOW
THERE WAS A DISCUSSION A YEAR
AND HALF AGO WITH THE FDA AND
THEY TALKED MORE ABOUT FOCUSING
ON THE PATIENT REPORTED OUT
COMES, I BELIEVE, I DON'T KNOW,
AMY YOU MAY KNOW MORE ABOUT THAT
THAN I DO BUT I THINK WE HAVE TO
KEEP THINKING ABOUT THIS.
>> YEAH, I THINK THAT I
COMPLETELY AGREE.
I THINK 1 OF THE PROBLEMS WITH
THE PATIENT REPORTED OUT COME AS
A COMMUNITY HAVEN'T GENERATED
ENOUGH DATA TO VALIDATE IT IT'S
LIKE PROs ARE LIKE ICE CREAM,
EVERYBODY'S GOT THEIR OWN
FAVORITE FLAVOR.
SO ACROSS STUDIES THEY'RE NOT
UTILIZING AND BUILDING THE DATA
TOWARDS, YOU KNOW ANYONE PATIENT
REPORTED OUTCOME.
SO I THINK THAT IT IS INCUMBENT
UPON THE COMMUNITY IN BRINGS
THESE DIFFERENT VOICES TOGETHER.
I THINK GETTING BACK TO PATIENT
ADVOCACY ORGANIZATIONS WE'RE
PRIMED TO DO THAT, EACH OF OUR
ORGANIZATION SYSTEM DEMONSTRATED
AN ABILITY TO BRING TOGETHER
DIFFERENT VIEW POINTS, DIFFERENT
ORGANIZATIONS TO WORK TOGETHER
TO THEY NOT NATURALLY OTHERWISE
DO SO AND I THINK THERE'S A LOT
OF INTEREST IN VALIDATING PROs
FOR PULMONARY FIBROSIS BECAUSE,
YOU KNOW FVC IS NOT NECESSARILY
A FEELS OR FUNCTIONS END POINT
FOR MANY PATIENTS SO IT DOESN'T
NECESSARILY TELL THAT TRUTH FOR
PEOPLE.
>> IF IT'S OKAY, I WOULD LIKE TO
ASK A QUESTION OF THE PANEL.
EACH OF THE DIFFERENT
ORGANIZATIONS HERE HAS REGISTRY
OR YOU KNOW PATIENT REGISTRY
EFFORTS.
I THINK THE CF FOUNDATION HAS
THE MOST ROBUST AND MOST
EXPERIENCED IN THIS AND THERE'S
A LOT TO BE LEARN FRIDAY THAT
BUT I ACTUALLY THINK THIS IS 1
OF THE MOST IMPORTANT THINGS AS
WE'RE MOVING FORWARD IS FOR
THERE TO BE EITHER DECENTRALIZED
OR MULTICENTER LARGE DATA SETS
BECAUSE WE ARE IN AN ERA OF
LARGE DATA AND TRYING TO
UNDERSTAND THESE THINGS AND
THEN, YOU KNOW WE COME UP WITH
THESE NEW IDEAS, THEY NEED TO BE
-- THEY NEED TO BE INVESTIGATED
FURTHER, INTERROGATED FURTHER,
VALIDATED FURTHER AND SO TO HAVE
SOMETHING THAT'S VERY WELL
CLINICALLY CHARACTERIZED AND
THEN ALSO HAS THOSE BIOLOGICAL
INFORMATION ASSOCIATE WIDE IT, I
THINK IS REALLY IMPORTANT.
SO MAYBE TALK A LITTLE BIT ABOUT
THAT.
WE HAVE SMALL, YOU KNOW, SMALL
GROUPS OF OUR RESPECTIVE
PATIENTS SO GETTING THOSE DATA
TOGETHER I THINK IS JUST VITALLY
IMPORTANT.
SO I WOULD LIKE TO HEAR FROM THE
EXPERIENCE THERE FROM THE OTHER
GROUPS IF I COULD.
>> IT TOOK US A LONG TIME TO
LAUNCH A REGISTRY BECAUSE WE
KNEW WE WANTED A CLINICAL REG
TREE AND WE KNEW WE WANTED IT TO
BE COLLECTED THROUGH THE SITES
BUT WE ALSO KNOW, THIS IS A
SMALL SUBSET OF OUR PATIENT
GROUP, SO WE ARE LOOKING NOW, TO
DO A BIG BROAD FUNNEL AND BRING
PEOPLE IN, MAYBE TO PATIENT
REPORTED REGISTRIES BUT I THINK
THE 1 THING THAT IT KIND OF
GETTING BACK TO RESOURCES AND
HOW MANY OF THESE RARE DEC
GROUPS ARE SO SMALL, REGISTRIES
ARE INCREDIBLY EBS PENSIVE AND I
THINK WITHOUT SUPPORT, IT'S JUST
SHOCKING TO ME HOW CRITICALLY
IMPORTANT THEY ARE AND YET IT IS
REALLY HARD TO GET THEM FUNDED.
AND I THINK WE'RE MISSING, I
THINK WE'RE MISSING A LOT OF
REALLY IMPORTANT DATA FROM A LOT
OF DIFFERENT DISEASES BECAUSE F
THAT.
>> I WILL SECOND HOW EFFORT
INTENSIVE MAINTENANCE OF THESE
REGISTRIES IS, OUR CLINICAL
TRIALS COORDINATORS DO IT MORE
OR LESS OUT OF THE GOODNESS OF
THEIR HEARTS BECAUSE IT'S REALLY
UNDERFUNDED AND IT'S HARD TO
KEEP ALL THE HOLES FILLED AND I
THINK FOR RARE DISEASES AND SOME
WAYS IT MIGHT MAKE MORE SENSE TO
HAVE A CONTACT REGISTRY WITHOUT
A LOT OF DEPTH AND IDENTIFY
WHERE PEOPLE ARE AND A LITTLE
BIT OF PHENOTYPIC INFORMATION
ABOUT THEM AND THEN WHEN IT
COMES TO TIME FOR THEM TO DO A
STUDY, YOU KNOW WHERE THEY ARE,
YOU CAN CONTACT THEM, CAN YOU
ANSWER SPECIFIC QUESTIONS, BUT
THE PROCESS OF COLLECTING
DETAILED DATA WITHOUT A QUESTION
IN MIND IS SOMETIMES KIND OF A
FOOL'S ERRAND AND YOU END UP
WITH A LARGE AMOUNT OF DATA THAT
NOBODY USES.
>> THAT'S EXACTLY WHERE WE
LANDED.
WE'RE THINKING OF DOING THE BIG
FUNNEL APPROACH AS A CONTACT
DATABASE AND THEN WHEN THERE'S
SPECIFIC NEEDS, WE HAVE A
PATIENT GROUP WE CAN GO BACK TO
AND GET THE INFORMATION THAT WE
NEED, BUT, YEAH, IT'S A LOT OF
WORK AND A LOT OF MONEY FOR
PATIENT ENTRY INTO THESE THINGS.
>> THANK YOU ALL.
THAT CONCLUDES THE PANEL FOR
SESSION 5.
WE'RE MAKING SOME MODIFICATIONS
TO THE AGENDA TODAY, SO THAT WE
CAN END A LITTLE EARLIER.
INSTEAD OF HAVING A 30 MINUTE
NETWORKING BREAK, WE WILL TAKE A
15 MINUTE BREAK CAN THAT CAN BE
A COFFEE OR BIOBREAK IF YOU WISH
OR YOU CAN STAY IN THE ROOM.
AND WE ARE GOING TO RETURN AT
2:30 EASTERN TIME TO START THE
BREAK OUTS, SO I WILL DISCUSS
THOSE A BIT BEFORE YOU ALL CAN
SELECT WHICH BREAK OUT YOU WOULD
LIKE TO PARTICIPATE IN AND HOPE
YOU STAY ON AND YOIN 1 OF THOSE
GROUPS TO GIVE YOUR FEEDBACK
ABOUT THE NEXT STEPS FOR
ADVANCING THERAPIES INTO THE
CLINIC. THANK YOU ALL.
WE'RE GOING TO BE MOVING INTO
THE BREAKOUT SESSIONS BUT I JUST
WANTED TO SPEND A COUPLE OF
MINUTES GOING OVER EACH OF THEM.
IF WE COULD PULL UP THOSE
SLIDES.ES
SO WE HAVE THREE BREAKOUT
SESSIONS AND REALLY WHAT THESE
ARE DESIGNED TO DO IS TO GET
FEEDBACK FROM YOU ALL ON SOME OF
THE CENTRAL THEMES FROM THE
WORKSHOP OVER THE PAST TWO DAYS.
AND TO REALLY THINK ABOUT
CRITICAL BARRIERS AND
FACILITATORS TO ADVANCING
INNOVATIVE THERAPIES FROM IDEA
THROUGH COMMERCIALIZATION AND
THE IND PATHWAY.
AND SO WE HAVE THREE BREAKOUT
SESSIONS, BREAKOUT SESSION ONE
IS ENTITLED MODELS AND METHODS,
COMPUTATIONAL, INVIE T IN VITRON
VIVO, COVERING TOPICS FROM
TUESDAY'S SESSION ONE, OVERVIEW
OF THE DRUG AND DEVICEICDEVELOPE
DISCUSSED THE MODELS AND TOOLS
THAT THE PULMONARY AND SLEEP
MEDICINE RESEARCH COMMUNITY
COULD USE TO START THINKING
ABOUT
SCREENING FOR DRUG
CANDIDATES AND GETTING INTO SOME
OF THOSE PRE-CLINICAL
IND-ENABLING STUDIES.
THE NEXT BREAKOUT SESSION IS
CALLED PATH FROM THE BENCH TO
COMPANY AND CLINIC.
THIS IS REALLY SORT OF A
BRIDGING SESSION THAT WILL COVER
TOPICS FROM TUESDAY'S SESSION
TWO, PARTNERING WITH REGULATORS
FOR SUCCESS AND SESSION THREE
DEFINING THE TARGET PROFILE, SO
HERE WE'LL SORT OF DISCUSS THE
MORE MATURE INNOVATION IDEAS
THAT HAVE SORT OF BRIDGED OUT OF
THE CONCEPT OUT OF THE LAB,
MAYBE INTO SMALL BUSINESS OR ON
TO SOME OF THE NIH GRANT
MECHANISMS OR EVEN WITH SEED
FUNDING FROM EITHER VENTURE
CAPITAL OR FROM OTHER SOURCES,
AND REALLY THINKING ABOUT THE
NEEDS THERE IN THAT SPACE TO GET
TO THE NEXT PLACE WHICH WOULD BE
FINISHING THOSE IND-ENABLING
STUDIES AND THEN MOVING INTO
CLINICAL TRIALS.
AND THE LAST SESSION TODAY WILL
COVER THE TOPICS FROM TODAY'S
SESSION, SESSION FOUR,
NAVIGATING CLINICAL TRIALS, AND
SESSION FIVE, SUCCESS STORIES
FROM THE LUNG AND SLEEP
COMMUNITY.
HERE WE REALLY WANT TO DISCUSS
SOME OF THE TOPICS THAT WERE
ADDRESSED IN THE FIRST SESSION
THINKING ABOUT EASE OF ACCESS TO
CLINICAL TRIALS, HOW YOU'RE
WORKING WITHIN YOUR ACADEMIC
INSTITUTION OR EITHER WITH AN
INDUSTRY PARTNER TO GET YOUR IP
PROTECTION, WORK ON CONTRACTS
AND THINGS LIKE TIK WOULD
HELP FACILITATE ADVANCEMENT OF
AN INDICATION AND MOVING INTO
THE IND AND INTO THE CLINICAL
TRIAL, AS WELL AS ANY OF THE
BARRIERS THAT WE'VE TALKED ABOUE
ACTUAL EARLY PHASE CLINICAL
TRIALS, WHETHER THAT BE PATIENT
ENGAGEMENT STRATEGIES, CLINICAL
TRIALS OUTCOMES, YOU KNOW,
AGAIN, SECURING CAPITAL AND
OTHER THINGS LIKE THAT.
SO THAT WILL COVER THAT SESSION.
AND WE'LL HAVE TWO CO-MODERATORS
IN THE SESSION THAT WILL REALLY
HELP G THEISCUSSION, AND
REALLY, WE REALLY HOPE THAT YOU
WILL SPREAD YOURSELF OUT EVENLY
ACROSS THESE DIFFERENT BREAKOUT
ROOMS AND THE DISCUSSANTS IN
THERE CAN REALLY START THINKING
ABOUT WAYS TO MORE OPENLY SHARE
SOME OF THEIR OWN EXPERIENCES
AND THE WORKSHOP PLANNING
COMMITTEE MEMBERS AND
COMODERATORS WILL HELP
FACILITATE THAT AND WILL BE
TAKING SOME NOTES.
WE'RE GOING TO BE IN THESE
BREAKOUT ROOMS, WE ORIGINALLY
SCHEDULED THEM FOR AN HOUR, BUT
I THINK THATN THE SMALL
NUMBERS OF INDIVIDUALS WEIVE
RIGHT NOW AT THE END OF THE DAY,
THIS IS GOING TO BE A LITTLE
MORE INTIMATE AND SO WE MAY NOT
NEED AS MUCH TIME.
SO I THINK WE'RE GOING TO PLAN
ON HAVING ABOUT 30 MINUTES IN
THAT DISCUSSION, AND THEN THE
MODERATORS CAN LET US KNOW IF WE
DO NEED ADDITIONAL TIME, BUT
WE'RE GOING TO CUT DOWN THE
BREAKOUT SESSION TO
AES LITTLE
BIT SHO AND THEN AFTER
THAT, WE WILLE ANOTHER
15-MINUTE BREAK.
THIS WILL ALLOW THE MODERATORS
TO DISCUSS THEIR NOTES AND THEN
WE'LL ALL COME BACK TO THIS MAIN
ROOM WHERE EACH OF THE BREAKOUTS
CAN REPORT OFF OF THEIR
DISCUSSION, AND THEN THE
WORKSHOP CO-CHAIRS WILL SORT OF
DISCUSS SOME OF THE CRITICAL
ELEMENTS WE WANT TO MAKE
RECOMMENDATIONS ON FOR THE
PULMONARY AND SLEEP RESEARCH
COMMUNITY, AND THINK ABOUT
STRATEGIES THAT WE CAN DO
TOGETHER AS A COMMUNITY TO
ADVANCE INNOVATIONS TO THE
CLINIC.
AND SO THAT'S REALLY GOING TO BE
THE STRUCTURE, AND SO NOW WE CAN
GO AHEAD AND OPEN UP THOSE
BREAKOUT ROOMS.
IF YOU WANT TO SEE WHAT THOSE
TITLES ARE AGAIN, THEY ARE IN
THE AGENDA AND YOU CAN
SELF-SELECT ANY OF THE BREAKOUT
ROOMS AND THEN WE'LL GIVE A FEW
MINUTES FOR PEOPLE TO GET INTO
THOSE ROOMS AND THEN WE'LL
BEGIN.
5 TO 10 MINUTES TO SUM UP THE
MAIN DISCUSSION POINTS FROM EACH
OF THE BREAKOUT ROOMS AND THEN
JEFF AND KATELYN, AS THE
WORKSHOP CO-CHAIRS, REALLY
TAKING THOSE IDEAS TO THINK
ABOUT THE RECOMMENDATIONS THAT
WE'D LIKE TO MAKE TO THE
RESEARCH COMMUNITY AND THAT
INCLUDES AT EVERY LEVEL, WHETHER
IT BE A PATIENT AND ADVOCACY
GROUP, CLINICIANS, INDUSTRY,
REGULATORS, FEDERAL GOVERNMENT,
WE'RE ALL UNDER THAT UMBRELLA
FOR CONSIDERING THESE
RECOMMENDATIONS AS BARRIERS AND
FACILITATORS TO GETTING THESE
WONDERFUL IDEAS THAT ARE
POTENTIAL INTERVENTIONS ALL THE
WAY THROUGH TO THE PATIENTS THAT
NEED THEM MOST.
SO WE'LL START WITH BREAKOUT
ROOM ONE.
>> IF THERE WERE TO BE A WINNER,
WE WOULD BE THE BEST BREAKOUT
ROOM, I'M JUST GOING TO GO AHEAD
AND PREFACE WITH THAT.
>> OH, YEAH, WE'RE BREAKOUT ROOM
1.
HEY.
>> HELLO, JOHN, NICE TO SEE YOU!
>> GOOD TO SEE YOU GUYS.
JOHN KENNEDY.
GOOD TO TALK TO EVERYONE.
SUCH A FANTASTIC MEETING.
YESTERDAY WAS AMAZING.
IN OUR BREAKOUT ROOM, WE HAD
SOME REALLY GREAT CONVERSATIONS.
AGAIN, OUR TITLE WAS MODELS AND
METHODS INCLUDING COMPUTATIONAL
IN VITRO AND I VEE VO.
IN IN VIVO.
I STARTED BY INTRODUCING MYSELF
IN SOME OF OUR WORK IN PEDIATRIC
INTERSTITIAL LUNG DISEASE,
GENERATING A SINGLE RNA SEQ --
KIDS WITH GENETIC PEDIATRIC
INTERSTITIAL LUNG DISEASE.
I DISCUSSED SOME OF OUR
CHALLENGES IN DOING THAT.
AND THEN WE TALKED ABOUT SORT OF
WHAT THE BIG SINGLE NUKE AND
SINGLE CELL MODELS THAT WERE OUT
THERE WERE, WHAT WAS DONE AND
WHAT WAS NEEDED TO BE DONE.
WE DISCUSSED A BIT ABOUT THE
DIFFERENCES BETWEEN SINGLE CELL
APPROACH AND THE SINGLE NUC
APPROACH, WHAT THE BENEFITS AND
DRAW BACKS OF EACH INCLUDING
WHAT OUR SAMPLE AVAILABILITY IS.
WE SPENT A BUNCH OF TIME TALKING
ABOUT A LUNG ON A CHIP MODEL,
BEEN AROUND FOR A LITTLE WHILE.
DEFINITELY A BUNCH OF ADVANCES,
WE SAW SUCH A GREAT PRESENTATION
YESTERDAY LOOKING AT OUR IMMUNE
CELLS MOVING.
WE TALKED ABOUT HOW COMBINING
EPITHELIAL, MESENCHYMAL, IMMUNE
AND LYMPHATIC TOGETHER IN THAT
SETTING IS VALUABLE BUT WE
TALKED ABOUT EXACTLY WHAT IS THE
RIGHT MODEL THERE.
WE TALKED ABOUT IN THE NEED PEDC
INTERSTITIAL LUNG DISEASE FIELD,
HOW SOME OF OUR FIBROTIC LUNG
DISEASES DUE TO IMMUNE
DYSREGULATION INCLUDING DEFECTS
IN COPA, DEFECTS IN STAT
PATHWAYS MIGHT BE NICE THERE FOR
MODELING THOSE.
THERE WAS A BIGGER THEME THAT
CAME OUT OVER AND OVER ABOUT
WHAT SAMPLES ARE AVAILABLE NOW.
AS WE TALK MORE AND MORE ABOUT
OUR PROJECT FOR THE CHILD
FOUNDATION DOING THE SINGLE NEUK
RNA SEQ AND THEN SPATIAL
TRANSCRIPTOMICS ON THE OLD
TISSUES, WE BROUGHT UP LUNG MAP
AND LUNG MAP BRIN DELL
REPOSITORY, WHICH BEAUTIFULLY
PRESERVES FROZEN EXPLANTS FROM
CHILDREN, SOME OF WHOM HAVE
GENETIC SURFACTANT DEFECTS OR
INTERSTITIAL LUNG DISEASE AND IS
A RESOURCE THAT'S AVAILABLE TO
THE COMMUNITY.
WE USE THAT IN OUR RESEARCH, AND
WE WERE FIRST OF ALL WANTING TO
REPLICATE THAT MORE, AND SECOND
OF ALL, WANTING TO SPREAD THE
WORD THAT THAT'S A TOOL FOR
RESEARCHERS AS WELL.
WE SPENT A LOT OF TIME TALKING
ABOUT THE COOL STUFF WITH THE
FERRET MODEL.
I GEEKED OUT ON THE ABERRANT
BASALOID POPULATION AND IF ANY
WORK HAD BEEN DONE IN
DEVELOPMENTAL STAGES OF THOSE
FERRETS BECAUSE AS A PEDIATRIC
FULL PULL MI KNOLL GIST, WE'RE
INTERESTED IN FIBROSIS THAT
ARISES VERY EARLY, SOMETIMES IN
THE FIRST WEEKS OR MONTHS OF
LIFE.
SO THAT LED US TO DISCUSSIONS
ABOUT FATE MAPPING OF DIFFERENT
LUNG CELL TYPES.
WHAT HAD BEEN PUBLISHED
INCLUDING SOME MOUSE WORK THAT
IS BEAUTIFUL AND WHAT WAS LEFT
TO BE PUBLISHED OR TO BE
INVESTIGATED, WE SEE THAT AS
POTENTIALLY A PRIORITY FOR
MODELS IN OUR FIELD AND WORTH
PUTTING SOME FUNDING BEHIND.
WE ALSO TALKED ABOUT -- WE GOT
INTO CONVERSATIONS ABOUT THIS
GREAT PARTNERSHIP THAT HAD
HAPPENED IN THIS CONFERENCE
BETWEEN REPRESENTATIVES FROM
VENTURE CAPITAL AND FROM
DIFFERENT AREAS OF INDUSTRY, AND
WE TALKED ABOUT HOW SOME OTHER
ORGANIZATIONS INCLUDING THE CZI
DO THAT REGULARLY AND HOW WE
SHOULD CONTINUE DOING THAT.
AND THIS LED US TO A
CONVERSATION OF THE MERITS OF
NEW DRUG NOVEL COMPOUNDS,
REPURPOSING COMPOUNDS AS
PEDIATRIC PROVIDERS, WE HAVE
EVEN FEWER TOOLS THAN WHAT I'M
SEEING ADULTS AND SOMETIMES
WE'LL LOOK TO REPURPOSE DRUGS
FIRST.
SO WE WONDERED HOW TO BALANCE
THAT AS WELL WITH OUR, PHARMA
AND OUR BC COLLABORATORS AS WELL
M AND THEN BI BIGGER CONVERSATIS
ON BIGGER BIOBANKS AND HOW WE
COULD GET TO THIS BIOMARKER
PROBLEM THAT WE'RE ALL
STRUGGLING WITH HOW TO IDENTIFY
DISEASE AND THEN HOW TO TRACK
OUR THERAPIES.
IN OUR CHILD'S MEETING LAST
MONTH, WE REALLY DISCUSSED
EXPANDING OUR CHILD REGISTRY TO
INCLUDE BLOOD SAMPLES AT
DIFFERENT TIME POINTS SO THAT
OUR INVESTIGATORS COULD DO DRUG
DISCOVERY AND DO THERAPY
MONITORING TOO.
A BIGGER EFFORT LIKE THAT IS
OBVIOUSLY HARDER BUT MAYBE
COMBINING MORE DISEASE-SPECIFIC
BIOBANKS INTO AT LEAST
INFORMATION THAT OTHERS COULD
HAVE ACCESS TO.
THOSE, I THINK, WERE THE BIG
THEMES THAT CAME OUT OF OUR
GROUP.
ANYONE ELSE HAVE ANYTHING THAT I
MISSED?
>> YOU DID A GREAT JOB
SUMMARIZING EVERYTHING WE TALKED
ABOUT.
>> THANKS.
>> ALL RIGHT, ROB.
OVER TO YOU, AND I'LL BACK YOU
UP IF NEEDED.
>> THANK YOU.
SO THIS WAS BREAKOUT SESSION TWO
WHICH IS CLEARLY THE BEST ONE.
AND THIS IS PATH FROM BENCH TO
COMPANY AND CLINIC.
SO JUST TO GIVE YOU HIGH LEVEL
OVERVIEW, WE FOUND FIVE AREAS
THAT ARE WORTH COMMENTING ON.
NUMBER ONE IS JUST HOW DO WE LET
EARLY STAGE INVESTIGATORS KNOW
THAT THERE ARE ADDITIONAL
RESOURCES OUTSIDE OF FEDERAL
FUNDING WHICH MAY BE SLIGHTLY
EASIER TO GET AND A LOWER BAR,
WHICH MIGHT HELP KIND OF FUND
THE EARLY DISCOVERY BEFORE IT'S
NIH-READY, WE THINK THAT'S
IMPORTANT.
AND THEN HOW CAN THE NIH START
TO EDUCATE PEOPLE ABOUT THAT.
SO FOR EXAMPLE, WHETHER IT'S THE
CF FOUNDATION, LIKE LOCAL SEED
FUNDING WHICH IS AT THE STATE OR
REGIONAL LEVEL OR BIOTECH HUBS,
FOR EXAMPLE, THEY HAVE THE NORTH
CAROLINA BIOTECH CENTER, BECAUSE
IT'S REGIONAL IT'S LIKELY THEY
HAVE LESS COMPETITIVENESS, A
LITTLE EASIER TO KIND OF DO THAT
AND THEN MAYBE THEY'LL BE
WILLING TO TAKE ON SOME MORE
RISK.
NUMBER TWO, THIS IS REALLY
GETTING STARTED IN DRUG
DISCOVERY AND KIND OF GETTING
OFF THE BENCH BEFORE WE EVEN GET
TO THE COMPANY.
SO THEN THE OTHER ONE IS
CREATIVE GROUND MECHANISMS.
WE'VE GOT THE R01s AND R21s,
ONCE YOU FORM THE COMPANY YOU
CAN DO THE STTRs AND SBRs
AND IN THE MIDDLE THERE'S STUFF
LACKING.
SO THERE COULD BE ONE -- IT'S
ALMOST LIKE AN STTR AT THE
UNIVERSITY BUT FEDERALLY THEY
CAN'T DO THAT SO WE'D HAVE TO
HAVE A NEW MECHANISM.
AND SOMETHING WHICH MAY HELP,
FOR EXAMPLE, IF YOU HAVE A DRUG
THAT WANTS TO BE REPURPOSED,
IT'S NOT NOVEL ENOUGH FOR AN
R01, IT COULD STILL EXTREMELY
VALUABLE AND MAY ACTUALLY GET TO
THE CLINIC.
SO THINGS LIKE THAT.
POINT NUMBER THREE WAS ARE
INSTITUTIONS A BARRIER TO DRUG
DEVELOPMENT AND THIS IS BOTH THE
ACADEMIC INSTITUTES OR THE NIH,
MAYBE IP IS NOT FULLY PROTECTED,
THERE COULD BE A BARRIER TO
PROGRESS, AGAIN, BOTH
INSTITUTIONAL -- IS TO -- DOES
IT IMPEACH -- CAN THAT BE LOOKED
AT, CAN THE NIH GUIDE THE INTS
INSTITUTIONS BETTER.
I THINK THERE WAS ALSO A
DISCUSSION ABOUT THE CULTURE AT
THE INSTITUTIONAL LEVEL.
SO FOR EXAMPLE, ACADEMIC
INDUSTRY, TRULY ARE THE R01s
AND -- THEN OBVIOUSLY LESS VALUE
IS PLACED ON INVESTIGATORS
GETTING DRUG DEVELOPMENT
FUNDING.
THERE COULD BE SOMETHING,
HOWEVER, THE DRUG DEVELOPMENT IS
ACTUALLY CENTRAL TOLL THE NIH'S
MISSION STATEMENT, SO COULD THE
NIH EITHER BY EDUCATING KIND OF
THE SENIOR ACADEMICS OR
INCENTIVIZING, SO THE BASIC
DISCOVERY TRACK -- MAYBE THE
ENTREPRENEUR TRACK OR THE
TRANSLATIONAL TRACK IS MORE
VALUABLE, THIS IS SOMETHING THAT
COULD BE AFFECTED.
AND SO THE QUESTION IS ALSO HOW
WOULD THE NIH DO THIS, BY
COMMUNICATION, TO MAKE THE
ACADEMICS AWARE THAT THE DRUG
DEVELOPMENT IS CENTRAL TO THEIR
MISSION STATEMENT, OR BY
SHIFTING RESOURCES.
AND THEN CAN THE NIH PUT IN MORE
TRANSLATION INVESTMENT BASICALLY
TO DO THIS.
SO POINT NUMBER FOUR IS, IT WAS
DEBATED -- SO YOU KNOW, COULD
THERE BE A NEW TYPE OF R01 SUCH
AS A TRANSLATIONAL R01 WHICH WAS
REALLY FOCUSED ON DRUG
DEVELOPMENT, BUT TO GET TO THE
TARGET SO YOU CAN GET GET
INVESTIGATORS OUT INTO THE OF TE
INDUSTRY AND INTO THE COMPANY.
I FOUNDED TWO COMPANIES, ONE GOT
TO PHASE TWO, ONE IS IN
PRE-CLINICAL DEVELOPMENT.
THE FIRST, I RAISED MONEY AND
LOST CONTROL OF THE COMPANY
QUITE QUICKLY.
THE SECOND I'VE RAISED SEVERAL
MILLION, IT'S GONE MUCH SLOWLY
BUT I THINK WE'RE IN MUCH
BETTER -- YOU MEAN, I'M A BIG --
I THINK MICHAEL BOLTSMAN -- I
WAS A BIG ADVOCATE FOR USING THE
FEDERAL DOLLARS TO GET AS
PREPARED AS YOU CAN BEFORE YOU
PARTNER UP BECAUSE I BELIEVE
THERE'S A LOT YOU CAN DO.
FOR EXAMPLE, TRANSLATION R01s
OR NEW FUNDING MECHANISMS COULD
BE REALLY HELPFUL FOR
INVESTIGATORS.
AND THEN THE LAST POINT WAS
ESPECIALLY THIS VENTURE
CAPITALISTS HARD TO SECURE, AND
SO THE NIH HAD A GREAT ROLE IN
HELPING PEOPLE GO OUT TO VCs.
FOR EXAMPLE, I KNOW THERE ARE
THINGS LIKE THE VENTURE SUMMIT,
LIKE ATS AND THINGS, BUT THERE'S
NO ONE SIZE FITS ALL SO -- ASK
PEOPLE ARE THEY READY TO GO OUT,
IS IT TOO SOON, AND REALLY HELP
PEOPLE GET READY.
SO THAT'S ALL I HAVE.
MARRAH ACTUALLY MADE MUCH MORE
EXTENSIVE NOTE.
I CHOSE NOT TO USE THEM AT THIS
POINT IN TIME.
I CAN GO BACK TO THEM OR
ANYTHING ELSE TO ADD?
>> NO, I THINK YOU COVERED IT.
I THINK A COUPLE OF OTHER THINGS
THAT WERE ANCILLARY TO SOME OF
THAT IS THE IDEA OF DECISION
POINT.
YOU TOUCHED ON THIS ABOUT, YOU
KNOW, LOSING COMPANY RIGHTS
VERSUS STAYING IN, AND WHETHER
OR NOT YOU WANT TO FOLLOW YOUR
SCIENCE ALL THE WAY THROUGH TO
THE END OR IF YOU WANT TO LET
GO, BECAUSE THAT'S A BETTER
OPPORTUNITY FISCALLY AND FOR THE
INTERVENTION ITSELF.
I THINK THAT'S A CRITICAL
QUESTION.
MIKE TOUCHED ON THIS AS WELL,
YOUR PERSEVERANCE AND POINT OF
ABILITY TO CONTINUE TO LEVERAGE
FEDERAL GOVERNMENT FUNDING AS
SECURE A RESOURCE TO STAY IN THE
SPACE BUT I THINK YOU VERY WEREY
ELOQUENT IN SAYING THAT IS SLOW
BECAUSE IT'S NOT THE SAME AS
RAISING VENTURE CAPITAL FUNDS
AND GETTING A LARGER AMOUNT OF
SEED MONEY INTO MOVING THINGS
ALONG.
SO THE BALANCE, I THINK, IS
SOMETHING THAT PEOPLE ARE STILL
THINKING ABOUT, AND HOW WE CAN
CONTINUE TO SUPPORT THEM BY
FINDING WAYS TO GET THEM TO SPIN
OFF TO DIFFERENT RESOURCES, I
THINK WAS A KEY THEME.
>> OKAYMENT WELL, I GUESS WE'LL
TRANSITION TO THE BEST FOR LAST
HERE, WITH THE THIRD GROUP,
WHICH WAS NAVIGATING CLINICAL
TRIALS AND PARTNERING PATIENTS.
I WOULD SAY THERE WAS REALLY
FOUR OVERALL MAIN ARCHING TOPICS
THAT WE TALKED ABOUT IN OUR
BREAKOUT.
I THINK THE FIRST ONE THAT
REALLY GENERATED A LOT OF
INTEREST WAS AROUND THE
POTENTIAL IMPORTANCE AND
OPPORTUNITY WITH INVESTIGATOR
INITIATED TRIALS.
THEY'RE SO PRAGMATIC, THERE'S
THE OPPORTUNITY FOR ACADEMIC
MEDICINE TO REALLY TAKE THE LEAD
ON A LOT OF THESE AND HELP
HOPEFULLY WITH SUPPORT FROM THE
NIH TO FINANCE THEM, BUT WE
CAN'T REALLY UNDERSCORE ENOUGH
THE IMPORTANCE OF THIS INITIAL
CLINICAL PROOF OF CONCEPT.
HOW YOU CAN TAKE A HANDFUL OF
PATIENTS, NOT THIS MORE
TRADITIONAL VERY EXTENSIVE
LARGER STUDY DEPENDING ON THE
PATIENT POPULATION, BUT THAT
INITIAL VERY EXPENSIVE LARGER
STUDY, TO REALLY INCENTIVIZE
GOING AFTER THESE VERY NICHE
SMALL PATIENT POPULATIONS AND IT
REALLY ALSO ADDRESSES THE ACCESS
PROBLEM FOR PATIENTS BECAUSE A
LOT OF TIMES IT'S THESE ACADEMIC
MEDICINE CLINICIANS WHO ARE
WORKING WITH THOSE PATIENTS IN
THEIR PRIVATE CLINICS AND CAN
ACTUALLY BRING THEM FORWARD IN A
VERY SUCCINCT MANNER.
SO WE THINK THERE'S A REAL
OPPORTUNITY THERE TO
PARTICULARLY FOR SOME OF THE
RARER LUNG DISEASES, TO REALLY
MAKE HUGE IMPROVEMENTS IN THE
SPACE AND LOWER THOSE BARRIERS
FOR CLINICAL DEVELOPMENT.
SO THAT WAS CERTAINLY ONE OF THE
BIG AREAS OF INTEREST.
I THINK ANOTHER BIG THEME WAS
REALLY TO HELP BETTER DEFINE THE
PATIENT POPULATION.
YOU KNOW, REALLY JUST THE ACCESS
TO ELECTRONIC MEDICAL RECORDS.
WE HAD HEARD AROUND THE PCB
FOUNDATION SOME OF THE WORK THAT
THEY HAD DONE TO TRY AND GAIN
ACCESS AND HOW CHALLENGING THAT
COULD BE, AND EVEN THEN WHEN YOU
DO GET ACCESS SOMETIMES TO BE
ABLE TO ACTUALLY PARSE OUT
ENOUGH INFORMATION TO ACTUALLY
DO SOMETHING WITH THAT
INFORMATION IS QUITE
CHALLENGING.
SO ANYTHING THAT CAN BE DONE TO
REALLY EDUCATE PATIENTS AND
REALLY RECRUIT THEM AS AN
OPPORTUNITY TO REALLY LEARN,
LEARN FROM THEIR MEDICAL
RECORDS, AND THIS ALSO COULD
POTENTIALLY UNLIKE BETTER
UNDERSTANDING OF THESE DISEASES,
WHICH THEN CAN -- YOU HAVE
SOMETHING LIKE IPF WAS ONE OF
THE GREAT EXAMPLES THAT WAS
RAISED, IDIOPATHIC IN ITS NAME,
IT JUST DOESN'T GENERATE A LOT
OF UNDERSTANDING AROUND THE
POTENTIAL FOR VERY SPECIFIC
GENETIC-BASED SUBPOPULATIONS
PERHAPS WITHIN THAT LARGER FIELD
OF THE DISEASE TO REALLY TARGET
IN ON.
SO THOSE ARE REALLY OPPORTUNITY.
THE POTENTIAL IMPORTANCE OF
NATURAL HISTORY STUDIES, YOU
KNOW, THOSE ARE THINGS THAT CAN
REALLY ATTRACT INDUSTRY
INVESTMENT IF THERE ARE
WELL-UNDERSTOOD PATIENT
POPULATIONS AND DISEASE
PROGRESSION, AND THOSE ARE KIND
OF THE SAFE HARBOR SPACE, IF YOU
WILL, THAT BOTH GOVERNMENT AND
ACADEMIC MEDICINE CAN HELP
PARTNER ON, WHERE IT'S REALLY
CHALLENGING IF -- WHEN INDUSTRY
HAS TO ALSO DEVELOP A NATURAL
HISTORY STUDY IN PARALLEL TO A
THERAPEUTIC AND IT'S ALMOST A
CONCURRENT DOUBLING OF EXPENSE
IF YOU WILL, SO IT FURTHER
RAISES THAT BARRIER PARTICULARLY
FOR RARE DISEASES TO MAKE IT
THAT MUCH MORE CHALLENGING,
WHEREAS THIS IS AN OPPORTUNITY,
PERHAPS, FOR ACADEMIC MEDICINE
OR THE GOVERNMENT TO START
REALLY UNDERSTANDING WHAT
DISEASE PROGRESSION LOOKS LIKE,
WHICH INEVITABLY INVITES MORE
RESEARCH BECAUSE AGAIN IT'S
AROUND LOWERING THOSE BARRIERS
AND IMPROVING THE CHANCE OF
SUCCESS WHERE WE DON'T HAVE TO
TRY AND FIGURE OUT THE
BIOMARKERS AS WE'RE ROLLING AND
WHAT SUCCESS LOOKS LIKE IN A
PATIENT POPULATION. SO WE THINK
THERE'S REAL OPPORTUNITY THERE.
WITHIN THE NATURAL HISTORY
STUDY, THE PCD GROUP ACTUALLY
ALSO SPOKE ABOUT THE IMPORTANCE
POF UNDERSTANDING THE ENTIRE
PATIENT POPULATION WHERE
POSSIBLE BECAUSE THEY HAD A LOT
OF GOOD GRAN ALREADY
UNDERSTANDING AROUND PEDIATRIC
PATIENTS BUT THEY'VE REALLY
STRUGGLED TO KIND OF BACKFILL
WITH WHAT DOES THAT LOOK LIKE IN
ADULTS?
AND THAT'S A GOOD LESSON TO
REALLY UNDERSTAND THAT IF YOU
FOCUS IN TOO MUCH INTENTIONALLY
BUT TOO MUCH ON A NICHE
SUBPOPULATION THAT CAN HELP YOU
IN SOME REGARDS BUT IT CAN ALSO
HURT YOU IN OTHERS.
AS WE HAD TALKED AROUND THE LAST
SESSIONS, PANEL DISCUSSION WAS
AROUND THE FOLKS HAVE BEEN TALK,
ABOUT, JUST REALLY THE
IMPORTANCE OF THERE REALLY
TRYING TO DEVELOP PHYSIOLOGICAL
BASED BIOMARKERS TO COMPLEMENT
MORE TRADITIONAL BIOMEDICAL OR
BIOLOGICAL BIOMARKERS OR THINGS
THAT ARE VERY QUANTIFIABLE.
BUT NOT ALL BIOMARKERS PRECEDE D
IN A LINEAR FASHION, SO THAT
MIGHT BE AN OPPORTUNITY TO AGAIN
AS PART OF SAY A NATURAL HISTORY
STUDY INVESTING MORE IN TRYING
TO UNDERSTAND HOW DIFFERENT
BIOMARKERS REACT, COUGH MONITOR,
REMOTE TYPE OF MONITORING OF
THESE END POINTS AS WE'VE HEARD
ABOUT.
THERE COULD BE A LOT OF VALUE IN
THIS SPACE, AND THAT, AGAIN,
LOWERS THE ACTIVATION ENERGY, IF
YOU WILL, FOR FURTHER INVEST M,
IF THERE'S A CLEAR GO/NO-GO FOR
PATIENT BENEFIT BASED UPON WELL
UNDERSTOOD BIOMARKERS, IT JUST
INVITES THAT MUCH MORE RESEARCH
IN THOSE SPACES.
THEN I THINK THE LAST TOPIC THAT
I RECALL WAS AROUND THE
IMPORTANCE OF BIOPSIES.
AND PARTICULARLY IN THE GENETIC
MEDICINE SPACE, IT'S EXTREMELY
IMPORTANT TO UNDERSTAND WHERE A
PATIENT STARTS OUT IN ORDER TO
BE ABLE TO ASSESS WHERE THEY'RE
GOING, AND I THINK THIS CAN BE
REALLY CHALLENGING AS WE'VE
HEARD IN THE CF SPACE AND IPF
AROUND THE LIMITED BIOPSIES THAT
ARE OUT THERE RIGHT NOW AND THE
CHALLENGES OF CONVINCING
PATIENTS WHAT THAT VALUE IS TO
GIVING IT NOT NECESSARILY END
STAGE DISEASE TYPE BIOPSIES, BUT
ALSO UNDERSTANDING THE
LONGITUDINAL DISEASE PROGRESSION
ASPECTS, AND JUST HOW IT'S SO
DIFFICULT TO UNDERSTAND
SOMETIMES WHAT THAT DISEASE
PROGRESSION LOOKS LIKE BECAUSE
MANY OF THOSE BIOPSIES JUST
SIMPLY AREN'T AVAILABLE FOR MANY
DIFFERENT DISEASES.
SO WE CONTINUE TO WORK THROUGH
AND TRY TO FIND INNOVATIVE OTHER
WAYS TO KIND OF GET SURROGATES
FOR THIS BUT ULTIMATELY THERE'S
NO SUBSTITUTE FOR HAVING THE
TRUE BIOPSIES.
JOHN, WAS THERE ANYTHING I
MISSED YOU WANTED TO TOUCH ON?
>> NO, I THINK YOU COVERED
EVERYTHING QUITE WELL.
>> GREAT.
THANK YOU.
>> SO I THINK FOR THE NEXT
STEPS, JUST THINKING ABOUT THE
THEMES ACROSS BOTH WORKSHOP
DAYS, AND SOME OF THE THINGS
THAT WE DISCUSSED IN THE
BREAKOUTS AS WELL AS ON THE
PANELS, I THINK THE CRITICAL
CHALLENGE HERE IS TO THINK ABOUT
WHAT THE COMMUNITY CAN AND
SHOULD DO, SORT OF
RECOMMENDATIONS AND IDEAS FOR
THE RESEARCH COMMUNITY VERSUS
WHAT WE CAN DO AT THE NIH TO
U.SUPPORT THOSE ACTIVITIES AS
WELL, LIKE WHAT SPECIFICALLY MAY
BE IN OUR DOMAIN AS
RECOMMENDATIONS FOR THINKING
ABOUT WAYS WE CAN LEVERAGE
EXISTING MECHANISMS, EXISTING
POLICIES AND THINGS LIKE THAT,
VERSES LIKE MAKING
RECOMMENDATIONS FOR THE
SCIENTIFIC AND CLINICAL RESEARCH
COMMUNITY, WHICH MAY BE HARD IN
THIS TOPIC AREA, BECAUSE WE HAVE
A LOT OF DIFFERENT STAKEHOLDERS,
RIGHT?
WE HAVE PATIENTS, ADVOCACY
GROUPS, INDUSTRY, WE HAVE
INVESTORS, REGULATORY BODIES AND
THEN WE HAVE THE ACTUAL
RESEARCHERS AND CLINICIANS
INVOLVED ACROSS THOSE.
SO I THINK THAT ACTION ITEMS
FROM THE WORKSHOP, WE DEFINITELY
WILL HAVE AN EXECUTIVE SUMMARY
WHICH WILL REFLECT A LOT OF
THIS, SO WE WANT TO MAKE SURE
THAT WE HAVE THOSE THEMES
ADDRESSED, AND CERTAINLY IF THE
GROUP WAS INTERESTED IN MAKING A
WHITE PAPER POSITIONAL
STATEMENT, WE COULD CERTAINLY
HELP SUPPORT THAT AS WELL.
AND THEN WE WANT TO CONTINUE TO
WORK IN THIS SPACE.
IT IS SORT OF NEW FOR US.
AGAIN, CATALYZE IS -- I'M NOT
THE LEAD OF CATALYZE, BUT WE HAD
THE LEAD OF CATALYZE HERE
YESTERDAY BUT THAT'S A PROGRAM
THAT'S A LITTLE BIT IN ITS
INFANCY.
AND THAT'S KIND OF WHY WE'RE
HERE, IS BECAUSE WE RECOGNIZE
THAT THOSE TYPES OF PROGRAMS ARE
NEEDED BUT THEN THERE ARE A LOT
OF OTHER AREAS THAT WE COULD BE
ADDRESSING BY WORKING TOGETHER
REALLY.
SO REALLY, KATELYN AND JEFF, IF
YOU HAVE IDEAS AND THINGS THAT
YOU THINK THAT WE SHOULD BE
CONVEYING TO THE COMMUNITY, WE'D
REALLY LIKE TO HEAR THAT.
>> I WAS GOING TO SAY, LADIES
FIRST, BUT -- NO, JUST -- I
THINK WE'VE TOUCHED ON A LOT OF
THOSE TOPICS.
I MEAN, I'M NOT AN EXPERT ON
DIFFERENT GOVERNMENT PROGRAMS
THAT ARE AVAILABLE ALREADY, BUT
IT JUST FEELS LIKE THESE NATURAL
HISTORY STUDIES, THE BIOMARKER
TYPE, FUNDING TO SUPPORT THOSE
ACTIVITIES ARE REALLY -- WILL
DIRECTLY BENEFIT SO MANY OF
THOSE INVESTED STAKEHOLDERS THAT
YOU'VE SPOKEN ABOUT TODAY,
MARRAH, AND THAT WE'VE ALL
DISCUSSED.
THOSE BENEFIT EVERYONE IN THE
PROCESS, AND I THINK ALSO WE'LL
DIRECTLY TRANSLATE TO PATIENT
BENEFIT OVERALL, SO I THINK
MECHANISMS AROUND THAT ARE A
GREAT PLACE TO START
POTENTIALLY.
>> CONTINUING THE CONNECTION OF
THE DIFFERENT SILOS OF RESEARCH
TOGETHER TO HAVE THESE
CONVERSATIONS, I THINK SERVES AS
A REALLY IMPORTANT SPARK TO MANY
OF THESE EFFORTS.
SO -- AND YOU KIND OF SEE PEOPLE
LIGHT UP IN A WAY THAT THEY
DON'T IN THEIR REGULAR JOB WHEN
THEY'RE ABLE TO KIND OF
CROSS-POLLINATE WITH THESE OTHER
DISEASE SPACES AND THAT
INTERACTION ONLY MAKES US
STRONGER, SO I THINK ONGOING
EFFORTS TO SUPPORT THAT, I THINK
A LITTLE BIT OF BRAINSTORMING
DISCUSSION ABOUT WHAT COULD
HAPPEN IN CONJUNCTION WITH ATS
AND ARE THERE WAYS TO FOCUS IN
ON SOME OF THIS KIND OF MORE
EARLY RESEARCH TO TRY TO CONNECT
PEOPLE IN THAT SPACE.
AND I THINK FROM THE COMMUNITY,
IT SOUNDS LIKE WE'VE GOT SOME
GOOD RECOMMENDATIONS FOR ONGOING
WORK PARTICULARLY AROUND STUDY
END POINTS AND HOW WE HELP THE
FDA WITH THE INFORMATION THEY
NEED TO MAKE DRUG APPROVAL
EASIER FOR US.
SO I FEEL LIKE A LOT OF THAT
CONVERSATION IS IMPORTANT AND
WILL CERTAINLY BE GOOD TO PUT IN
WRITING.
YEAH.
I CAN'T HAVE THE FINAL WORD.
>> I'M GOING TO ASK JOHN IF HE
HAD ANY OVERARCHING THEMES OR
THINGS THAT HE WANTED TO TOUCH
ON AS WELL.
>> NO, NOT PARTICULARLY.
I THINK THIS HAS BEEN A GREAT
DISCUSSION, I THINK IT'S BEEN A
REALLY GREAT TWO DAYS, LOTS OF
FANTASTIC TALKS AND
PRESENTATIONS.
AS MARRAH SAID, I THINK THERE'S
A LOT OF INFORMATION THAT WE'LL
TAKE AND WORK TOGETHER TO PUT
TOGETHER THE EXECUTIVE SUMMARY
AND DISSEMINATE FINDINGS FROM
THIS TO THE COMMUNITY.
SO BACK TO YOU.
>> I THINK THAT THIS DOES POSE A
CHALLENGE AS KATELYN YOU NOTED,
LIKE THE CONVERSATION CAN'T
REALLY STOP WITH TODAY.
AND WHILE WE CAN CONTINUE THE
MOMENTUM, MAYBE SMALL PIECES OF
WORKING TOGETHER WITH THE
ADVOCACY GROUPS THAT HAVE
PLATFORMS FOR CONNECTIONS TO
INVESTIGATORS AND PATIENTS AND
HOW THEY INCENTIVIZE INVESTMENT
FROM THE COMMUNITY WHICH THE
RESOURCES THEY HAVE, AND SO HOW
WE COULD HELP MAKE THOSE
CONNECTIONS AT SMALLER LEVELS,
WHETHER THAT'S HAVING A LITTLE
MORE FOCUS ON RARE DISEASES AND
UNMET NEEDS AT THE INNOVATION
SUMMIT AS YOU'RE THINKING ABOUT
ATS AND I KNOW THAT MIKE HAD
MENTIONED YESTERDAY THINKING
ABOUT OTHER CONFERENCE AND
PLATFORM LEVELS FOR THIS TO
HAPPEN IN THE LUNG COMMUNITY.
AND YOU KNOW, THINKING THE ABOE
DIFFERENCES BETWEEN INSTITUTES
AND CENTERS, WE ALL SORT OF SET
OURSELVES AROUND A MISSION THAT
COMPLEMENTS THE NIH'S MISSION AS
ROB HAD MENTIONED, WE WANT TO
TURN DISCOVERIES INTO HEALTH,
AND THIS CONVERSATION IS REALLY
SAYING THERE ARE BARRIERS TO US
DOING THAT, SO WE NEED TO FIGURE
OUT WHAT THOSE BARRIERS ARE AS A
COMMUNITY AND LEVERAGE WHAT WE
HAVE AND THEN ALSO FIGURE OUT
WAYS TO BE MORE CREATIVE
TOGETHER.
AND THIS IS I THINK OF CRITICAL
IMPORTANCE TO THE RARE DISEASE
COMMUNITY AND UNMET NEEDS WHY WE
HAD THAT FOCUS OF THIS
PARTICULAR WORKSHOP BECAUSE
THERE ARE A LOT OF DISEASES WITH
EITHER SOMEWHAT DISEASE
MODIFYING THERAPIES OR NO
THERAPIES, AND ESSENTIALLY MOST
OF THEM HAVE NO CURES.
AND SO THAT'S LIKE REALLY THE
HEALTH EQUITY ISSUE FOR THOSE
INDIVIDUALS WITH HIGH MORBIDITY
AND MORTALITY IS SOMETHING
THAT'S A CRITICAL IMPORTANCE, SO
REALLY JUST FIGURING OUT WAYS TO
BREAK THOSE BARRIERS, AND NIH IS
JUST ONE PIECE AND SO HOW WE CAN
BE MORE CREATIVE WITH OUR
FEDERAL PARTNERS, I THINK IS
SOMETHING THAT IS GOING TO BE
SOMETHING WE SHOULD CONSIDER AND
CONTINUE TO WORK ON, ESPECIALLY
IN THE RARE DISEASE SPACE.
SO A LOT OF IDEAS CAME OUT
AROUND THOSE THEMES AND REALLY
DO APPRECIATE ALL THE SPEAKERS
AND THE TIME THAT THEY'VE GIVEN
TODAY, AND ALSO FOR YOU ALL,
HELPING PLAN THIS WONDERFUL
WORKSHOP AND DEDICATING YOUR
TIME AND EFFORT TO ALL OF IT.
AND IT REALLY MUCH APPRECIATED.
SO WITH THAT, I THINK WE CAN
CLOSE OUT, UNLESS YOU HAVE
ANYTHING ELSE YOU WANT TO SAY
BEFORE WE DO?
>> JUST THANK YOU, MARA AND
JOHN, FOR HOSTING, YOU DO AN
AMAZING JOB HOSTING THIS.
THRILLED TO HELP, AND I THINK
THERE WAS A LOT OF PROGRESS
DURING THIS MEETING, SO THANK
YOU.
>> YES, THANK YOU, EVERYBODY.
>> THANK YOU, GUYS.
>> THANK YOU.
>> BYE.
>> THANK YOU.