>>I CAN'T TELL WHAT YOU A GREAT
PLEASURE IT IS TO SEE EVERYONE
HERE.
NON-PROFIT FORUM IS REALLY A
HIGHLIGHT FOR NINDS, CERTAINLY,
EVERY YEAR.
AND IT'S GREAT TO SEE PEOPLE
OUTSIDE OF THE SQUARES AND IN
PERSON.
I THINK A LOT OF THE
INTERACTIONS WE'VE HAD OVER THE
YEARS HAVE BEEN QUITE VALUABLE
AND I'M HOPING THAT THIS KIND OF
HYBRID BOTH ALLOWS LOTS OF
PEOPLE TO BE INVOLVED AND PEOPLE
WHO TRAVEL IN HOPEFULLY CAN GET
INTO SOME REALLY GOOD
CONVERSATIONS THAT MOVE YOUR
AGENDAS FORWARD AND OUR COMMON
AGENDA WHICH IS TO FIND MORE
EFFECTIVE TREATMENTS FOR A
VARIETY OF NEUROLOGIC DISEASES.
UNFORTUNATELY, WE SHOULD ALWAYS
START BY APOLOGIZING FOR LACK OF
EFFECTIVE THERAPIES FOR MANY OF
THE DISEASES.
BUT OUR INSTITUTE AND PEOPLE WHO
WORK HERE AND YOU ARE ALL
DEDICATED TO TRY AND CHANGE THAT
AND I THINK WE'LL HEAR TODAY
THAT THERE ARE THESE WINDOWS
OPENING UP FOR NEW THERAPIES, SO
YOU'LL HERE THAT PARTICULARLY IN
THE DISCUSSION TODAY ABOUT GENE
THERAPIES.
THESE ARE REALLY KIND OF CUTTING
EDGE.
IT'S A REALLY NEW AREA OF
SCIENCE, TO TELL YOU THE TRUTH,
THAT WE HAVE GREAT EXPECTATIONS
FOR.
BUT IT'S GOING TO BE A PROCESS
OF LEARNING HOW TO DO THIS, BOTH
REPLACING GENES THAT ARE MISSING
IN PEOPLE WHO HAVE NEUROGENETIC
DISORDERS AND TURNING OFF GENES
THAT ARE MUTATED AND OF COURSE
TROUBLE, BUT BOTH TECHNOLOGIES
NOW EXIST.
AND SO ON THE ONE HAND IT'S AN
ENGINEERING PROBLEM OF MAKING IT
HAPPEN IN AN EFFECTIVE WAY, BUT
ALSO LEARNING A LOT ABOUT THE
SAFETY ISSUES AS WE MOVE
FORWARD.
A LOT OF THE DRUGS THAT WE'VE
BEEN TRYING, SOMETIMES THEY HAVE
SOME EFFECT, SOMETIMES THEY
DON'T HAVE ANY EFFECT.
BUT THEY DON'T OFTEN HOLD THE
PROMISE OF REALLY, YOU KNOW, A
CURE AS NEW GENE THERAPIES DO.
SO WE'RE GOING TO HEAR TODAY
FROM TERRY PIROVOLAKIS, A
CHAMPION IN MOVING THIS FIELD
FORWARD, AND SUCCESS STORIES.
WE DID HAVE IN OUR DISORDERS WE
HAD THREE DIFFERENT NEW DRUGS
APPROVED OVER THE LAST YEAR,
NEUROLOGIC DISORDERS, SO YOU'LL
BE HEARING SUCCESS STORIES
THERE.
AND THEN I THINK WE'RE HOPING
THAT AS ALWAYS, THIS IS A WAY IN
WHICH THE NON-PROFIT
ORGANIZATIONS CAN COMMUNICATE
WITH NINDS.
NINDS CAN TELL YOU KIND OF WHAT
WE'RE UP TO.
BUT WE REALLY WANT TO LISTEN TO
YOU.
YOU ARE ACTUALLY OUR
CONSTITUENCY.
SO AS YOU KNOW, NINDS, WE'RE
VERY HAPPY TO TAKE YOUR
DONATIONS EVERY APRIL 15.
SO KEEP PAYING YOUR TAXES.
BUT THE IDEA IS IT'S NOT OUR
MONEY.
IT'S THE TAXPAYERS' MONEY, AND
THE PURPOSE IS TO MOVE THE
THERAPIES FORWARD FOR YOUR
DISEASES.
SO WE REALLY WANT TO HEAR FROM
YOU, AS WELL AS TELL YOU WHAT
OUR THOUGHTS ARE GOING FORWARD.
AND OF COURSE IT'S A REAL
PARTNERSHIP AND THIS IS REALLY
THE MEETING IN WHICH WE KIND OF
GET TO HEAR FROM SO MANY
DIFFERENT GROUPS.
AND THEN ALSO A CHANCE FOR
DIFFERENT GROUPS TO TALK TO EACH
OTHER AND GET LESSONS LEARNED.
EACH OF HAVE YOU YOUR OWN
CHALLENGES AS YOU MOVE YOUR
DISEASE AREA FORWARD AND YOUR
FOUNDATIONS FORWARD, AND THERE'S
A MIX OF PEOPLE HERE DOING IT
FOR MANY DECADES, SOME PEOPLE
STARTING UP.
SO IT'S ALSO A CHANCE TO LISTEN
TO EACH OTHER.
EVERYBODY HERE IS INCREDIBLY
GENEROUS WITH THEIR THOUGHTS AND
TIME, I'M SURE WOULD LOVE TO
HELP YOU AS YOU MOVE THROUGH
YOUR FOUNDATION PROGRESS.
SO WITH THAT I'D LIKE TO TURN IT
OAF TO OUR KEYNOTE SPEAKER,
TERRY PIROVOLAKIS, TO TELL THE
STORY OF WHAT GOT HIM INTO THIS
IN THE FIRST PLACE, WHICH IS A
VERY POIGNANT STORY.
BUT I THINK THE OTHER PART IS
HOW TERRY WAS ABLE TO SEE FROM
HOW HE GOT INTO THIS IN THE
BEGINNING HOW IT COULD BE
SOMETHING MUCH, MUCH BIGGER.
AND WE'VE BEEN REALLY OVERJOYED
TO BE ABLE TO WORK WITH HIM AND
LOOK FORWARD TO WORKING WITH HIM
IN THE FUTURE ON PUSHING A
NUMBER OF GENE THERAPIES INTO
CLINICAL TRIALS.
SO, TERRY?
>> HI, EVERYBODY.
IT'S A REAL HONOR TO BE HERE.
FOUR YEARS AGO, I WAS IN A ROOM
JUST LIKE THIS ONE DOWNSTAIRS,
JUST ONE MONTH GREEN INTO THIS
NEW EXPERIENCE I WAS GOING
THROUGH TO SAVE MY SON MICHAEL.
IT'S A TRUE HONOR TO BE HERE
TALKING ABOUT MY JOURNEY AND
SUPPORT FROM NIH AND EVERYBODY
THAT SUPPORTED ME THROUGH THE
CRAZY DREAM I'M GOING TO TALK TO
YOU ABOUT.
IT'S A GREAT HONOR.
HANG YOU -- THANK YOU FOR HAVING ME
I'M TERRY PIROVOLAKIS.
THE LAST 20 YEARS OF MY LIFE
I'VE BEEN AN I.T. DIRECTOR FOR
LARGE BANKS ACROSS CANADA.
I'LL TELL A STORY ABOUT MY SON'S
JOURNEY, MY FAMILY'S JOURNEY,
FOR A CURE FOR MY SON.
MY WIFE IS GEORGIA, MY DAUGHTER
ZOE, MIDDLE SON ZACH, THE GRUMPY
FUR BALL IS MICHAEL.
HE WAS BORN DECEMBER 17, 2017.
A NORMAL HEALTHY BIRTH, HOME IN
THREE HOURS.
WE THOUGHT THE LIFE WOULD
PROGRESS LIKE THE OTHER
CHILDREN.
FIVE MONTHS AFTER BIRTH WASN'T
LIFTING HIS HEAD, 10th
PERCENTILE FOR HEAD GROWTH.
KEEP AN EYE ON HIM BUT SHOULD
OUTGROW IT.
DON'T BE CONCERNED.
AT SIX MONTHS AFTER BIRTH, WE
VISITED A PEDIATRICIAN, WE
STARTED DOING INTENSE PHYSICAL
THERAPY, AND NOTICED HE HAD
LITTLE OF TONE.
HIS HEAD WAS IN THE FIFTH
PERCENTILE AT THAT POINT IN
TIME.
HE STARTED REACHING FOR THINGS,
NO BIG DEAL.
AND WE CONTINUED ON AND THOUGHT
SOMETHING THAT HE WILL OUTGROW.
EIGHT MONTHS AFTER BIRTH,
INFECTIOUS DISEASE, I WAS DOING
WORK IN LATIN AMERICA, THOUGHT
MAYBE HE CONTRACTED ZIKA.
WE DID ALL THE TEST THERE IS.
AT THIS POINT HE STILL WASN'T
REACHING MILESTONES, WELL
BEHIND.
HIS HEAD WAS AT THE 3rd
PERCENTILE BUT SITTING UP AND
CONTINUING TO MOVE ALONG.
AT TEN MONTHS ALL THE INFECTIOUS
DISEASES CAME BACK RULED OUT.
NEUROLOGY DID AN MRI SEVERE
MICROCEPHALY, ABNORMAL WHITE
MATTER, TONE WAS IMPROVING.
WE KNEW SOMETHING WAS WRONG AND
PRAYED MICHAEL WOULD GET BETTER
BUT THIS WAS SOMETHING WE
COULDN'T PRAY AWAY.
AT 12 MONTHS WE RULED OUT ALL
THE DISEASES ON THE PANELS.
HE WAS NEGATIVE 3 PERCENTILE IN
HEAD GROWTH.
HE BEGAN PULL TO STAND, BEGAN TO
CRAWL.
HE WAS MAKING IMPROVEMENTS.
WE WERE SENT TO NEUROLOGY AT
THIS POINT TO DO A REPORT.
ON APRIL 2, 2019, MICHAEL
DIAGNOSED WITH SPASTIC
PARAPLEGIA TYPE 50, TOLD THERE
WAS VERY LITTLE KNOWN, IT CAUSES
MICROCEPHALY AND EPILEPSY,
QUADRIPLEGIA BY SECOND DECADE.
I WAS IN A FOG, WHAT'S GOING ON.
GET THE EMERGENCY ROOM READY,
WE'LL TAKE WHATEVER WE NEED OUT
OF ME.
THE DOCTOR SAID SOMETHING YOU
CAN'T DO WITH A GENETIC
CONDITION, GO HOME AND LOVE HIM,
ENJOY HIS LIFE AND THROUGH
THERAPY TRY TO MOVE HIM ALONG.
WE WERE TOLD SAVING MICHAEL WAS
IMPOSSIBLE.
FOR US IMPOSSIBLE WAS DOING
NOTHING.
WE KNEW WE WOULD GO ANYWHERE, DO
ANYTHING, GIVE EVERYTHING TO
SAVE MICHAEL.
I DECIDED I THERE WAS NOTHING
GOING TO STOP ME TO FIND A
TREATMENT FOR MY SON.
I CAME TO THE NIH.
YOU CAN SEE THAT'S FOUR YEARS
ALMOST TO THE DAY, I WENT TO
SHEFFIELD, MET AN EXPERT IN GENE
THERAPY, PUT UP A POSTER,
WANTED, A CURE FOR MICHAEL.
I MET SIX OF THE SEVEN WORLD
EXPERTS, PEOPLE AT NIH, FDA.
I ASKED IF YOU WERE TO TREAT
YOUR SON OR YOUR CHILD, WHAT
WOULD YOU DO?
THEY ALL SAID GENE THERAPY.
THE SECOND THING I SAID, WHO
WOULD YOU GO WITH?
ONE RECOMMENDATION, WE'LL GET TO
IN A MINUTE.
I ATTENDED FOOD CAMP AND EVERY
CONFERENCE FOR THE NEXT TWO
YEARS.
WE COLLABORATED WITH NIH.
REVERSE MORTGAGED OUR HOME,
SPENT OUR LIFE SAVINGS TO GET
THINGS STARTED.
A MONTH AND A HALF TO THE DAY
THAT MICHAEL WAS DIAGNOSED, WE
HIRED DR. GRAY AND DR. CHEN AT
THE UNIVERSITY OF TEXAS
SOUTHWESTERN MEDICAL CENTER TO
MAKE US THE GENE THERAPY WE WERE
LOOKING FOR.
AT THIS POINT UNFORTUNATELY WE
REALIZED WE HAD TO RAISE $3
MILLION, AT LEAST $3 MILLION.
AND WE DECIDED TO GIVE IT A TRY
AND HOPEFULLY PEOPLE WOULD HEAR
THE STORY AND HELP US.
OVER THE NEXT FOUR YEARS, THREE
YEARS, WE DECIDED TO DO
EVERYTHING WE COULD.
TOLD THE COMMUNITY ABOUT IT.
A WEEK LATER THEY HAD A BEER
WORKS EVENT, MADE A BEER FOR
HIM, $25,000 AFTER ONE WEEK OF
COMING OUT WITH OUR STORY.
THE GENTLEMAN ON THE LEFT, HE
RECYCLES, EVERY MONTH I'LL BE
HERE WITH MONTH.
SURE ENOUGH HE SHOWS UP, WITH A
CHECK IN HAND OR CASH, FOR THE
LAST FOUR YEARS.
THIS IS WHERE OUR JOURNEY BEGAN.
I'LL PLAY A VIDEO.
RIGHT AFTER WE CAME OUT WITH THE
STORY THE NEWS CHANNELS PICKED
IT UP.
IN ONE DAY, 3 MILLION VIEWS,
$160,000, ONE VIDEO ALONE.
♪
>> HI, BABY.
>> WE'RE GOING TO CURE HIM.
>> OR GIVE HIM THE BEST SHOT.
♪
>> A PRETTY HAPPY KID, IN
GENERAL.
>> MICHAEL IS A HAPPY LITTLE
GUY.
HE WORKS REALLY HARD TO DO BASIC
THINGS THAT OTHER KIDS DO
NATURALLY.
HE NEVER GIVES UP.
KEEPS GOING.
HE TRIES WITH ALL HIS WILL TO DO
SIMPLE TASKS LIKE, YOU KNOW,
CRAWLING AND WALKING, FEEDING
HIMSELF, THINGS WE ALL TAKE FOR
GRANTED.
INITIALLY IT WAS HARD.
IT'S STILL HARD.
EVERY DAY IS A LITTLE HARDER
BECAUSE MICHAEL HAS NOW STARTED
TO NOT REACH THE MILESTONES HE
SHOULD BE REACHING.
HE'S NOT WALKING.
HE'S NOT TALKING.
THAT AFFECTS YOU INTERNALLY AS A
FAMILY.
♪
>> THERE'S NOTHING.
THERE'S NO DRUG, THERE'S NO
TREATMENT.
FOR MICHAEL'S SPECIFIC DISEASE.
>> WHEN WE WERE TOLD ABOUT
MICHAEL'S DIAGNOSIS, THEY JUST
SAID, GO HOME AND JUST LIVE YOUR
LIFE.
BUT DON'T EXPECT MUCH FROM YOUR
SON.
HE WILL BE IN A WHEELCHAIR,
NON-VERBAL, HE WILL BE DELAYED.
AND THERE'S NOTHING WE CAN DO
FOR YOU.
>> DOING NOTHING IS IMPOSSIBLE.
WE CAN'T JUST SIT BACK AND SAY,
MICHAEL CAN FALL APART AND
THAT'S OKAY.
THAT'S NOT OKAY FOR US.
WE'LL DO EVERYTHING POSSIBLE.
>> THERE'S A PROCESS THAT COULD
HELP MICHAEL, BUT IT INVOLVES
THIS VERY EXPENSIVE APPROACH.
>> ALZHEIMER'S DISEASE, MULTIPLE
SCLEROSIS, PARKINSON'S DISEASE,
ALS, AND I COULD GO ON AND ON,
ALL THESE COMMON DISEASES ARE
GENETIC DISEASES THAT ARE MORE
COMPLEX, MEANING MORE THAN ONE
GENE IS INVOLVED.
TO FIX THOSE DISEASES, WE NEED
TO LEARN FIRST HOW TO FIX THE
DISEASES WHERE SINGLE GENES ARE
DEFECTIVE SUCH AS MICHAEL'S
DISEASE.
IT IS THE RESEARCH IN THESE RARE
TERRIBLE DISEASES OF CHILDREN
THAT WILL BE THE SPRINGBOARD FOR
US TO FIGURE OUT HOW TO TREAT
COMMON DISEASES THAT AFFLICT
EVERY ONE OF US.
>> HIS PROGNOSIS IS THE FUTURE
LOOKS BLEAK.
HE CAN'T FIGHT FOR HIMSELF, BUT
THAT'S WHY WE'RE FIGHTING TO DO
IT FAST AND QUICK.
SO WE'RE JUST HOPEFUL.
SO HOPEFUL THAT WE MAKE IT IN
TIME.
>> OVER THE NEXT FOUR YEARS WE
DID HUNDREDS OF EVENTS, GALAS,
BALL TOURNAMENTS, NIGHTCLUBS.
WE DID BOWL-A-THONS, MARATHONS,
YOU NAME IT, WE DID IT.
WE TRIED EVERYTHING HUMANLY
POSSIBLE TO RAISE THE MONEY WE
NEEDsED.
WE WERE FOUND OUR COMMUNITIES
CAME TOGETHER.
90% WERE ORGANIZED BY SOMEONE
ELSE, WE JUST SHOWED UP.
THEY GAVE US THE MONEY.
WE MOVED ON, INCREDIBLE TO HAVE
THIS MUCH SUPPORT.
MICHAEL WAS PROGRESSING, ALMOST
WALKING AT THIS TIME.
AT THE SAME TIME THE DISEASE WAS
KICKING IN, CAUSING SEIZURES,
UNFORTUNATELY AFTER ONE 3-HOUR
LONG SEIZURE, HE LOST THE
ABILITY TO BECOME VERBAL AND
HASN'T COME BACK.
THE COVID LOCKDOWN HAPPENED.
WE WERE THINKING OH MY GOD,
FORGET RAISING MONEY AND GENE
THERAPY, HOW DO WE HAVE HIM NOT
LOSE THE FUNCTIONS HE TRIED TO
KEEP.
I TRIED CALLING ALL THE POOL
COMPANIES, I NEED MICHAEL TO
CONTINUE THERAPY, CAN YOU
INSTALL A POOL, I'LL PAY
WHATEVER YOU WANT.
THIS VIDEO IS WHAT HAPPENED THE
WEEKEND AFTER.
AT THE HEIGHT OF COVID THE
COMPANY DONATED THE POOL, HIS
HOCKEY TEAM INSTALLED IT.
WE HAD MICHAEL SWIMMING THE NEXT
DAY, INCREDIBLE.
IT SHOWS YOU COMMUNITY IS REALLY
NEEDED TO HELP, YOU KNOW, WITH
THIS TERRIBLE DISEASE AND
RAISING SUCH MONEY.
WE WERE THINKING NOW WE HAVE
MICHAEL IN THERAPY, WE HAVE TO
RAISE MONEY AGAIN.
AND I STARTED RIDING A BIKE, MY
WIFE IS LIKE WHY DON'T YOU GET
YOUR BIKE 4,000 KILOMETERS.
HOLD ON HERE.
I'M LYING ON THE GROUND AFTER
TEN.
WE GOT TO SET EXPECTATIONS
REASONABLY.
I SAID IF I WAS TO RIDE FROM
TORONTO TO OTTAWA DO YOU THINK
YOU COULD ARRANGE FOR ME TO MEET
THE PRIME MINISTER OF CANADA?
IF YOU DO IT, WE'LL ARRANGED.
I TRAINED EVERY THIRD NIGHT,
NINE TO TWO IN THE MORNING, RODE
AS FAR AS I COULD THOSE
EVENINGS.
MY PARENTS AND I -- MY PARENTS
BEHIND ME PROTECTING MOW ME SO
HE DON'T GET RUN OVER, 400
KILOMETERS A DAY TO GET TO
OTTAWA.
THAT'S MY MOM ELBOW PUMPING THE
PRIME MINISTER.
WE PLEADED WITH HIM NOT TO HELP
MICHAEL BUT TO CREATE A RARE
DISEASE CENTER OF EXCELLENCE IN
CANADA.
WE RAISED $168,000 DURING THAT
ONE RIDE.
IT WAS AN EXPERIENCE I'LL NEVER
FORGET.
I SHOULD HAVE KEPT RIDING
BECAUSE I GAINED A LOT, BUT IT
WAS A GREAT EXPERIENCE.
AN AMAZING RESEARCHER WHO WORKS
AT THE NIH, THE FIRST THING WAS
SHE CAME BACK INTO THE OFFICE
WAS TO TEST THE VECTOR ON
MICHAEL'S CELLS.
THIS IMAGE RIGHT HERE TO APPLY
TO THE FDA, THIS WAS THE
CATALYST.
SECOND WE SHOWED IT IN CELLS WE
COULD START TOXICOLOGY.
THIS SHOWED THE HIGHER THE DOSE
WE DID, THE MORE CELLS WERE ABLE
TO RECOVER IN FIBROBLASTS.
THIS WAS THE PRECIPICE TO MOVE
FORWARD.
AND THEN WILDTYPE ANIMALS WERE
INJECTED, ONE MONTH, FIVE
MONTHS, ONE YEAR, THE EXPRESSION
CONTINUED AND GOT BETTER FROM
THE TRANSGENE WE INJECTED.
WE DID HAVE ONE PROBLEM.
IN OUR HIGH DOSE GROUP WE HAD
THREE ANIMALS THAT HAD ADENOMAS,
BUT THANKFULLY ONE OF THE
COMPANIES SHOWED THAT 53% OF
MALE MICE 12 TO 15 MONTHS
NATURALLY GET ADENOMAS, SO
INSTEAD OF THE PROGRAM BEING
OVER IT WAS JUST SOMETHING WE
HAD TO (INDISCERNIBLE).
THE BIG QUESTION, WE HAVE ALL
THIS DATA NOW, DO WE MANUFACTURE
CONCURRENTLY AND RISK
$4.5 MILLION?
THE ANSWER WAS YES, WE DID THAT.
WHICH WAS CRAZY.
WE DOSED THE RATS, DOSED
NON-HUMAN PRIMATE, SHOWING GOOD
DISTRIBUTION.
WE SHOWED THE MICE WERE ABLE TO
RECOVER HIND LEG INJECTIONS,
AFTER TREATING MOUSE, RATS,
NON-HUMAN PRIMATE, DOSED
MICHAEL, THE HIGHEST DOSE EVER
GIVEN.
AND THANKS TO THESE AMAZING
COMPANIES AND COLLABORATORS,
FROM ACROSS THE WORLD, WE
RECEIVED HEALTH CANADA APPROVAL
DECEMBER 30, AND MY SON WAS
DOSED ON MARCH 24 OF LAST YEAR
WITH THE GENE THERAPY WE MADE
FOR HIM.
WE WEREN'T DONE.
WE WANTED TO HELP MORE CHILDREN,
WE HAD THREE DOSE, WE DOSED TWO
MORE, TWO MONTHS AND FIVE MONTHS
AGO, AT UNIVERSITY OF TEXAS
SOUTHWESTERN MEDICAL CENTER,
PART OF A PHASE 1/2 THAT WE
APPLIED FOR.
ONE THING WE REALIZED DURING
THIS JOURNEY IS AFTER YOU
MANUFACTURE THE DRUG AND DOSED
PATIENTS, IT'S NOT FINANCIALLY
VIABLE TO CONTINUE TO DO THIS.
FOR YOU TO MAKE ONE DOSE IT
COSTS ABOUT A MILLION DOLLARS.
TO TREAT THAT CHILD COST COSTS
ANOTHER MILLION CHILDREN, THE
ONLY WAY IS TO GET THE DRUG
APPROVED SO INSURANCE COMPANIES
AN GOVERNMENTS WILL PAY FOR THE
DRUG.
IT'S SOMETHING WE REALIZED ALONG
THIS JOURNEY.
IF YOU LOOK AT WHAT WE DID, I'LL
POINT OUT A COUPLE THINGS.
FROM THE TIME WE STARTED TO THE
TIME WE DOSED MICHAEL IN THREE
YEARS, ONE CRAZY THING WE DID
WAS WE HAD OUR CLINICAL BATCH
MADE BEFORE THE NON-HUMAN TOX
STUDY WAS FINISHED.
IF THAT CAME BACK NEGATIVE WE
WOULD HAVE LOST ALL
$4.5 MILLION.
AND IN TOTAL IT COST US
$4.5 MILLION.
WE WERE THANKFUL ENOUGH THAT
JACK'S CORNER AND FOUNDATION
COLUMBUS WAS ABLE TO PAY FOR THE
TWO CHILDREN TO BE DOSED.
AT UTSW.
THIS IS OUR MASTER PLAN, WE
DOSED MICHAEL, PART OF THE PHASE
1/2 IN CANADA, APPLYING TO THE
FDA FOR NATURAL HISTORY TO DO
EIGHT PATIENTS, HOPEFULLY FIND
EFFICACY ENDPOINT OR BIOMARKER
APPROVAL FOR ACCELERATED
APPROVAL BASED ON FUNDAMENTAL
APPROVAL WE CAN'T LEAVE AN OPEN
IND, DRUGS HAVE TO BE TAKEN ON
OR WE'LL NEVER GET TO THE REST
OF THE KIDS, IT'S JUST NOT
FINANCIALLY AVAILABLE.
THEN IT TOOK A VILLAGE OF
PEOPLE, LITERALLY HUNDREDS OF
PEOPLE TO DO WHAT WE DID FOR
MICHAEL AND THESE OTHER
CHILDREN.
NOW AT THE NIH I'M ABLE TO THANK
THE PEOPLE INVOLVED HERE,
INSTRUMENTAL IN MAKING THIS WORK
AND MAKING THIS HAPPEN.
THE TEAM YOU SEE HERE ARE
HELPING US MOVE THIS FORWARD OR
ARE HELPING US WITH OUR NEW
COMPANY WE'RE WORKING ON.
THESE ARE HEROES, ALL THESE
PEOPLE ON THESE IMAGES ARE
HEROES, SAVING LIVES EVERY DAY.
I WANT TO QUICKLY GO THROUGH HOW
BIG THE PROBLEM IS.
RARE DISEASES ARE HUMANITY LEVEL
PROBLEMS.
THERE'S MORE THAN 10,000 RARE
DISEASES.
THEY EFFECT MORE THAN 400
MILLION PEOPLE, 1 IN 10 ARE
AFFECTED.
95% HAVE NO TREATMENT.
AND MORE THAN 3,000 CHILDREN DIE
EVERY SINGLE DAY.
THIS NUMBER BLEW MY MIND.
I CAN'T BELIEVE THAT THIS MANY
CHILDREN ARE DYING FROM RARE
DISEASES EVERY DAY.
WHEN YOU LOOK AT IT, PARENTS
LIKE ME, WE CAN'T LIVE IN FEAR.
WE CAN'T HAVE A BAG SITTING IN
OUR ROOM, WAITING FOR US TO RUN
TO THE EMERGENCY ROOM BECAUSE
OUR CHILDREN MIGHT DIE OR ARE
GOING TO GO INTO A SEIZURE.
WE CAN'T HAVE OUR CHILDREN
LIVING IN PAIN, GOING THROUGH
TESTS AND SUFFERING FROM THESE
DISEASES.
WE SHOULDN'T HAVE TO BURY OUR
CHILDREN BECAUSE OF RARE
DISEASE.
THESE DISEASES WITH BE TREATED,
CAN BE CURED.
WE JUST HAVE TO FIGURE OUT A WAY
FOR THIS FINANCIAL PROBLEM THAT
WE HAVE.
AND EVERY MINUTE, EVERY DAY,
EVERY MONTH, EVERY YEAR IS LOST
TRYING.
FOR THE DOCTORS AND COMPANIES IN
THE ROOM, I PLEAD WITH YOU TO
HELP RARE DISEASES IF YOU CAN.
HELP FAMILIES LIKE MINE.
HELP US GET THROUGH WHAT WE'RE
DOING.
BECAUSE WE NEED YOUR HELP.
WE CAN'T DO THIS ALONE.
I NEVER DID IT ALONE, AND I HOPE
YOU REACH OUT TO RARE DISEASE
FAMILIES AND HELP US ALONG THIS
JOURNEY.
THAT'S THE MAIN REASON I STARTED
ELPIDA THERAPEUTICS, I REALIZED
I WANTED TO MAKE A SMALL DENT,
TO TRY TO TREAT THESE DISEASES,
GET THEM APPROVED.
WE STARTED IN MAY, WE WERE THEN
CREATING A PARTNERSHIP, THE GOAL
TO TAKE PROGRAMS
NON-COMMERCIALLY VIABLE, LESS
THAN 300 IN THE WORLD, FROM
SELECTION TO BLA, GET THE DRUG
APPROVED IN THE HANDS OF
CORPORATIONS LIKES ROCHE,
NOVARTIS, PFIZER, TO DO MORE
PROGRAMS.
WE'VE TAKEN ON TWO PROGRAMS.
SPG-50, MY SON, CMT4J, AND IN
CONTRACT TO TAKE ON THREE MORE,
TO GET THESE TREATED BY 2025, TO
GET AN ENDPOINT AND SHOW
CHILDREN IMPROVE, WE'LL BE ABLE
TO CHANGE THEIR LIVES.
AND I WANT TO THANK THE BGTC FOR
BELIEVING IN US, A SMALL
COMPANY, ONE PERSON AT THE TIME,
TO MOVE FORWARD AND HELP THESE
CHILDREN WITH THESE RARE
DISEASES.
THANK YOU.
I THINK WE'RE OPEN FOR
QUESTIONS.
IF ANYBODY HAS ANY.
HOW IS MICHAEL?
HE'S -- IT'S INTERESTING.
HE WAS DOING NINE WEEKS OF
INTENSE THERAPY AT A HOSPITAL IN
CANADA.
AND THEN WE WERE -- HE GOT SICK.
WE WERE AT THE HOSPITAL, HE GOT
C. DIFFICILE, IT'S A TERRIBLE
STOMACH INFECTION.
HE LOST TEN POUNDS, COULDN'T GO
TO SCHOOL FOR SIX MONTHS, SOME
DAYS COULDN'T EVEN GET OUT OF
BED.
WE HAD TO CARRY HIM DOWNSTAIRS.
HE'S JUST GETTING BACK TO WHERE
HE WAS BEFORE, COGNITION
SIGNIFICANTLY IMPROVE, ABLE TO
COMMUNICATE MUCH BETTER.
HIS MOBILITY, WHERE HE WOULD
HAVE BEEN WALKING, UNFORTUNATELY
HE'S JUST CATCHING UP NOW.
THE OTHER TWO CHILDREN ARE DOING
AMAZING, AND WE'RE HAPPY WITH
THE RESULTS SO FAR.
>> QUESTIONS?
>> HI.
GREAT TALK.
>> THANK YOU.
>> SO, MICHAEL'S CONDITION IS
REALLY ULTRA RARE, IS THERE A
THRESHOLD FOR WHEN A CONDITION
BECOMES MORE FINANCIALLY VIABLE?
>> YEAH, THE NUMBER IS AROUND
2,000 PATIENTS WORLDWIDE.
SO THERE'S PROBABLY A FEW
THOUSAND DISEASES THAT FALL
UNDER THAT THRESHOLD.
PERFECT.
WELL, IF THERE'S NO MORE
QUESTIONS WE'LL INTRODUCE RON
FOR THE NEXT TALK.
>> I'M STILL RON BARTEK, FARA,
MY WIFE AND I FOUNDED 25 YEARS
AGO WHEN OUR SON KEITH WAS
DIAGNOSED -- IT'S HARD TO SAY 25
YEARS AGO.
I'M GOING TO BE BRIEF AND GET
OUT OF THE WAY OF THESE
WONDERFUL PANELISTS FOR A
WONDERFUL DISCUSSION OF THE
THING THAT TERRY SO INSPIRINGLY
INTRODUCED, THAT OF GENE
THERAPY.
JUST A BIT ABOUT MY BACKGROUND.
MY WIFE AND I BEGAN
COLLABORATING WITH, WORKING WITH
NINDS, EVEN BEFORE WE
ESTABLISHED FARA, MET OUR
PROGRAM DIRECTOR 26 YEARS AGO,
BEGINNING OUR PROCESS WITH THIS
WONDERFUL INSTITUTE.
I WAS ABLE TO -- A PROGRAM
DIRECTOR TOOK US TO OUR FIRST
NATIONAL ADVISORY COUNCIL
MEETING IN THE MAIN BUILDING,
AND THAT STARTED THE BALL
ROLLING OF A WONDERFUL
COLLABORATION OVER THOSE 25
YEARS.
CULMINATING -- NOT REALLY
CULMINATING, BUT INCLUDING A
FOUR-YEAR STINT ON THE NATIONAL
ADVISORY COUNCIL OF NINDS.
AND REALLY PLEASED TO SAY ALSO
GOT THE OPPORTUNITY TO SERVE ON
THE NATIONAL ADVISORY COUNCIL OF
NATIONAL CENTER FOR NCATS, AND
THIS SOURCE OF ONE OF OUR
PANELISTS, P.J. BROOKS, IS A KEY
MEMBER OF THAT TEAM.
ALL THAT COLLABORATION, YOU
KNOW, HAS REALLY STIMULATED OUR
RESEARCH IN OUR RARE DISEASE, A
RARE NEUROMUSCULAR DISEASE.
I'LL SAY THAT OUR DEEP
INVOLVEMENT WITH NINDS HAS
PROVEN TO BE ABSOLUTELY
BENEFICIAL TO OUR SCIENTISTS.
ONCE WE STARTED SEARCHING AS A
TWO-WAY COMMUNICATOR BETWEEN
NINDS AND OUR SCIENTISTS,
INFORMING OUR SCIENTISTS OF
OPPORTUNITIES HERE AT THE
INSTITUTE, INFORMING THE
INSTITUTE OF THE WORK GOING ON
AMONG OUR SCIENTISTS, YOU CAN
IMAGINE HOW SIGNIFICANTLY ROSE
THE NUMBER OF NIH GRANTS TO OUR
RESEARCH SCIENTISTS.
I JUST COULDN'T ENCOURAGE YOU
MORE TO USE THESE OPPORTUNITIES
TO MEET YOUR PROGRAM DIRECTORS
AS WE DID.
SOME OF YOU HAVE ALREADY SPENT
TIME THIS MORNING WITH YOUR
PROGRAM DIRECTORS.
IF YOU HAVEN'T DONE THAT, PLEASE
DO IT.
IT'S A PHENOMENALLY IMPORTANT
AND GOOD WAY TO GET TO KNOW THE
WORKINGS OF THE INSTITUTE AND
COMMUNICATE THOSE WORKINGS TO
YOUR WHOLE COMMUNITY, YOUR
PATIENT FAMILIES, YOUR
SCIENTISTS, AND SO FORTH.
I'D LIKE TO TAKE A MOMENT HERE.
I GET EMOTIONAL.
I'M SORRY.
TO APPLAUD THE NINDS FOR ITS
TREMENDOUS DEVOTION TO ALL OF US
AND THE WORK THAT THEY DO FOR
ALL OF OUR RARE DISEASE
PATIENTS.
NOW I WILL TRY TO SOBER UP AND
TURN TO THIS WONDERFUL PANEL.
OUR INTENTION IS TO EXPAND ON
THE PARTNERSHIPS AND
COLLABORATIONS THAT TERRY
INTRODUCED, IN ADVANTAGING THE
WORK IN THIS VERY IMPORTANT
FIELD OF GENE THERAPY, IMPORTANT
TO I THINK EVERYBODY IN THE ROOM
AND ONLINE, WITH EMPHASIS ON THE
ROLE PATIENTS AND ADVOCATES
PLAY, AND PLAY MORE PROMINENTLY.
I'M GOING TO KICK OFF BY
INTRODUCING AND EACH WILL
INTRODUCE THEMSELVES.
BUT I WANT TO INTRODUCE LEAD-OFF
HITTER, I'M A BASEBALL FAN.
DR. COURTNEY SILVERTHORN.
>>NINDS IS AN EARLY AND STRONG
SUPPORTER OF THE WORK OF THE
BESPOKE GENE CONSORTIUM, REALLY
THE GOAL TO STREAMLINE THE
PROCESS OF BRINGING SOMETHING
FORWARDS THROUGH PRE-CLINICAL
TESTING INTO A FIRST-IN-HUMAN
CLINICAL TRIAL.
AND SO WE HAVE BEEN ON AN
18-MONTH JOURNEY TO IDENTIFY
PROMISING CANDIDATES FOR
CLINICAL TRIAL APPLICATIONS, HAD
A VERY OPEN PROCESS THROUGHOUT
2021 INTO 2022, TO IDENTIFY WHAT
ULTIMATELY LANDED ON EIGHT
CLINICAL TRIALS IN EIGHT RARE
DISEASES WITH THE GOAL OF USING
THESE AS TEST CASES TO MOVE THE
ENTIRE FIELD FORWARD.
IF YOU TAKE NOTHING ELSE HOME
FROM THE MESSAGE OF THE BGTC, WE
HAVE 8 DISEASES IN THE PORTFOLO
WE WANT TO HELP EVERY GENE
THERAPY THAT COULD MOVE FORWARD
IN THIS SPACE BY PROVIDING
MANUFACTURERS PROTOCOLS,
REGULATORY TEMPLATES, RESOURCES
PEOPLE NEED TO HAVE THE MORE
STREAMLINED PATH FORWARD INTO
THEIR JOURNEY AND INTO THEIR
TREATMENTS FOR THEIR CHILDREN.
THE BESPOKE CONSORTIUM IS PART
OF THE ACCELERATED MEDICINES
PARTNERSHIP PROGRAM.
THIS DATES BACK TO 2014 WITH THE
FOUNDATION OF THREE PROJECTS,
THREE DISEASE AREAS, FOCUSED ON
PRE-COMPETITIVE ADVANCEMENTS.
IN GENE THERAPY THE AREA WE
IDENTIFIED WAS ABOUT THE PROCESS
AND THE PROCESS OF THE PLATFORM.
THAT WAS WHERE WE FOCUSED OUR
EFFORTS.
WE'RE THE ONLY PROGRAM THAT IS
IN DISEASE AGNOSTIC STATES,
FOCUSED ON THAT PROCESS RATHER
THAN DISEASE OR DISEASE AREA.
MY BACKGROUND IS NOT GENE
THERAPY, IT'S IN PHARMACOLOGY
WHICH I HAVE NOT USED SINCE
2009, MY EXPERTISE IS IN
PUBLIC/PRIVATE PARTNERSHIPS AND
I'VE BEEN GIVEN THIS INCREDIBLE
OPPORTUNITY TO SHEPHERD THE WORK
THAT SO MANY PEOPLE ARE DOING.
I LOOKED ACROSS OUR STEERING
COMMITTEES AND OUR WORKING
GROUPS, AND OUR ACADEMIC
INSTITUTIONS THAT ARE RECEIVING
FUNDING FROM THE PROGRAM.
IT'S WELL OVER 200 INDIVIDUALS
WHO ARE CONTRIBUTING TO THE
PROCESS.
SO IT'S JUST SUCH AN OPPORTUNITY
TO BE PART OF THAT AND TO
OVERSEE THE PROGRESS THAT WE'RE
STARTING TO MAKE.
REALLY EXCITED TO DISCUSS MORE
TODAY.
>> THANK YOU VERY MUCH, DR.
SILVER THORN.
BATTING SECOND IS COMING TO US
VIRTUALLY, DR. P.J. BROOKS.
ARE YOU THERE?
>> GOOD MORNING, EVERYBODY.
CAN YOU SEE ME AND HEAR ME?
>> WE CAN HEAR YOU.
WE CANNOT YET SEE YOU.
>> HOW ABOUT NOW?
>> THAT WAS WALTER BY THE WAY,
P.J.
>> OKAY.
NOW YOU CAN SEE ME?
SO, YEAH, HAPPY TO BE HERE.
AND SORRY I CAN'T BE THERE IN
PERSON.
I HAD ANOTHER COMMITMENT.
BUT HAPPY TO PARTICIPATE.
SO I WANTED TO TELL YOU ABOUT
SOME THINGS WE'RE DOING AT
NCATS.
AT NCATS, WE TRY TO FOCUS ON
COMMONALITIES ACROSS MULTIPLE
DISEASES.
AND THAT SEEMS LIKE THE MOST
PRACTICAL WAY TO DEAL WITH THE
THOUSANDS OF RARE DISEASES AND
PARTICULARLY THE RARE GENETIC
DISEASES.
AND SO WE HAVE -- ARE INVOLVED
IN MULTIPLE PROGRAMS TO DO THIS,
ONE IS THE BESPOKE GENE THERAPY
CONSORTIUM YOU HEARD ABOUT FROM
COURTNEY.
ANOTHER ACTIVITY THAT WE HAVE
GOING ON AND WE BEGAN THIS
BEFORE THE BGTC, THE PAVE GT
PROGRAM, PLATFORM VECTOR GENE
THERAPIES.
THE IDEA OF THIS ONE IS IF WE
CAN USE THE SAME AAV VECTOR FOR
MULTIPLE DISEASES AND KEEP
EVERYTHING THE SAME EXCEPT FOR
THE THERAPEUTIC INSERT, THAT WE
OUGHT TO BE ABLE TO IDENTIFY
MORE STREAMLINED WAYS OF
STARTING UP CLINICAL TRIALS AND
TO DO THAT WE'VE SELECTED FOUR
DIFFERENT DISEASES, ALL DISEASES
HAVE NO COMMERCIAL INTEREST, AND
ALL DISEASES UNDER STUDY AT THE
NIH CLINICAL CENTER.
TWO OF THESE ARE METABOLIC
DISEASES.
AND TWO ARE NEUROMUSCULAR
JUNCTION DISEASES.
AND THE IDEA IS THAT WOULD KEEP
EVERYTHING THE SAME, EXCEPT THE
THERAPEUTIC INSERT.
WE WOULD PROPOSE TO THE FDA
CERTAIN WAYS OF STREAMLINING THE
PROCESS.
THEY WOULD RESPOND TO US IN THE
INTERACT AND PRE-IND MEETINGS,
AND WE WOULD MAKE THIS
INFORMATION PUBLIC.
R. SO THAT EVERYBODY CAN LEARN
FROM US AS WE GO THROUGH THE
PROCESS.
AND ONE OF OUR PARTNERS IN THIS
IS DR. CARSON BONNEMAN FROM
NINDS, TWO STUDIES NEUROMUSCULAR
DISEASES.
WE'VE MADE THIS WORK PUBLIC,
RELEASED ORPHAN PRODUCTS DRUG
DESIGNATION WE FILED FOR A FIRST
DISEASES PROPRIONIC, YOU CAN
DOWNLOAD THAT AND FIND THE
PRODUCT TO DEVELOP THE ORPHAN
PRODUCTS.
THESE ARE THE THINGS WE'RE DOING
IN THE GENE THERAPY SPACE.
ALONG WITH THE BGTC, OF COURSE.
IN ADDITION TO GENE THERAPY WE
INTERESTED IN GENOME EDITING,
PERHAPS MORE BROADLY APPLICABLE
PLATFORM FOR GENETIC DISEASES.
I'M ONE OF THE CO-COORDINATORS
WITH TIM LAVOTE FROM NINDS OF
THE SOMATIC CELL GENOME EDITING
PROGRAM, FUNDED BY THE NIH
COMMON FUND.
WE'RE NOW ABOUT TO START OUR
SECOND YEAR, SECOND PHASE.
THE FIRST PHASE WAS FOCUSED ON
THE DEVELOPMENT OF TECHNOLOGIES,
AND TOOLS TO ACCELERATE GENOME
EDITING INTO THE CLINIC.
WE'RE NOW IN THE SECOND PHASE,
FOCUSED MORE ON GETTING INTO THE
CLINIC, AND GETTING APPROVED
INDs TO MAKE AVAILABLE TO
OTHERS SHOULD THEY CHOOSE TO
PICK UP AND EVEN SUPPORTING
CLINICAL TRIALS OF GENOME
EDITORS WITH REQUIREMENTS THAT
THESE ARE DONE AS THERAPEUTIC
PLATFORM FOR MULTIPLE DISEASES,
SOCK WE THINK IS VERY IMPORTANT.
WE TRIED TO DEVELOP THERAPEUTIC
PLATFORMS AS THERAPEUTIC
PLATFORMS FROM THE BEGINNING,
AND TO GET AWAY FROM THE IDEA OF
DEVELOPING ONE DRUG FOR ONE
DISEASE THAT IS JUST GOING TO
TAKE FAR TOO LONG GIVEN THE
AMOUNT OF DISEASES THAT WE HAVE
TO DEAL WITH.
AND FINALLY THE GENOME EDITING
SPACE SOMETHING WE'RE VERY
EXCITED ABOUT AS YOU PROBABLY
KNOW DELIVERY OF GENOME EDITORS
INTO THE NERVOUS SYSTEM IS A BIG
CHALLENGE.
SO ONE OF THE COMPONENTS OF THE
PROGRAM WE HAVE IS ACTUALLY A
PRIZE COMPETITION FOR NON-VIRAL
TECHNOLOGIES TO DELIVER GENOME
EDITORS ACROSS THE BLOOD-BRAIN
BARRIER INTO SUBSTANTIAL NUMBERS
OF CLINICAL RELEVANT CELLS IN
THE BRAIN.
THIS IS A PRIZE COMPETITION, IN
THAT REGARD QUITE DIFFERENT THAN
A TYPICAL NIH GRANT.
IT'S OPEN TO ANYONE.
AND I'LL PUT THE LINK IN THE
CHAT AS WE'RE TALKING SO PEOPLE
CAN SEE IT AND WE WOULD VERY
MUCH EN ENCOURAGE PEOPLE TO
DISSEMINATE THE INFORMATION.
IF WE CAN DEVELOP A NON-VIRAL
TECHNOLOGY TO CROSS THE
BLOOD-BRAIN BARRIER THAT WOULD
HAVE A HUGE IMPACT ON THE FIELD
AND TO TREAT MULTIPLE GENETIC
DISEASES THAT AFFECT THE NERVOUS
SYSTEM.
SO I THINK I'LL STOP THERE AND
HAND IT OVER I BELIEVE TO GOPA.
>> THANK YOU VERY MUCH, P.J.
WE CAN SEE YOU NOW.
>> I GUESS THAT'S GOOD.
I DON'T KNOW.
PROS AND CONS.
>> DR. GOPA RAYCHAUDHURI OF THE
FDA IS NEXT.
>> THANKS VERY MUCH.
I'D LIKE TO THANK MEETING
ORGANIZERS FOR THE OPPORTUNITY
TO PARTICIPATE IN THIS
CONFERENCE, TO BE PART OF THE
PANEL.
THE TOPIC PARTNERSHIPS AND
COLLABORATION IS INCREDIBLY
IMPORTANT, REALLY TIMELY GIVEN
THE TREMENDOUS EXPANSION WE'RE
SEEING IN THE GENE THERAPY FIELD
RIGHT NOW.
SO I WANT TO START BY SAYING
THAT THE FDA'S HIGHLY COMMITTED
TO FACILITATE THE DEVELOPMENT OF
SAFE AND EFFECTIVE THERAPIES TO
ADDRESS UNMET MEDICAL NEEDS FOR
PATIENTS WITH RARE AND VERY RARE
DISEASES.
THIS IS A VERY HIGH PRIORITY FOR
US, AND WE'RE TAKING A
MULTI-PRONGED APPROACH.
SO I WANT TO SHARE A FEW AREAS
WHERE WE'RE ENGAGED AND HAPPY
OVER THE COURSE OF THE SESSION
TO EXPAND ON ANY OF THESE.
ONE AREA IS PROVIDING FDA
GUIDANCE.
THERE IS A LOT OF -- THERE'S A
LOT OF NEED TO PROVIDE GUIDANCE
TO HELP FACILITATE THE
DEVELOPMENT OF THESE NOVEL
PRODUCTS.
AND SO OUR OFFICE OF
THERAPEUTICS PRODUCTS HAS BEEN
VERY PROLIFIC IN PROVIDING
GUIDANCE FOR GENE THERAPIES AS
WELL AS FOR TOPICS THAT ARE
PARTICULARLY IMPORTANT FOR RARE
DISEASES.
THAT'S ONE AREA.
WE ENCOURAGE SPONSORS TO
COMMUNICATE WITH US THROUGHOUT
THE ENTIRE PRODUCT DEVELOPMENT
PROCESS.
BUT FOR RARE DISEASES IT'S
PARTICULARLY IMPORTANT TO ENGAGE
EARLY, EVEN IN THE PRE-IND
SPACE.
I CAN TOUCH ON SOME OF THE
PROGRAMS THAT WE HAVE THAT ARE
ENCOURAGING PRODUCT DEVELOPERS
TO COME IN EARLY TO DISCUSS THE
DEVELOPMENT PLANS BEFORE YOU
EVEN GET STARTED.
I'M SURE YOU'RE AWARE WE HAVE A
NUMBER OF DIFFERENT PROGRAMS,
EXPEDITED PROGRAMS, TO
FACILITATE PRODUCT DEVELOPMENT
FOR DISEASES THAT ARE SERIOUS OR
LIFE-THREATENING, AND CERTAINLY
MANY, MANY RARE DISEASES FALL
INTO THAT CATEGORY.
AND THEN THE FOURTH THING I WANT
TO EMPHASIZE IS PARTNERSHIPS,
THE TOPIC OF WHAT WE'RE
DISCUSSING TODAY.
WE VERY ACTIVELY ENGAGED IN
PARTNERSHIPS.
WE'RE VERY -- WE'RE AN INTEGRAL
PART OF THE BESPOKE CONSORTIUM,
BUT MANY EARS BECAUSE THIS IS
CRITICAL TO HAVE A SEAT AT THE
TABLE AND WORK WITH COMMUNITIES
AS THESE PRODUCTS ARE DEVELOPED.
WHAT I WANT TO REALLY EMPHASIZE
IS THE ROLE OF PATIENT
ENGAGEMENT IN THIS.
IT'S CRITICAL FOR PATIENTS TO
WORK RIGHT FROM DAY 1 WITH
PRODUCT DEVELOPERS TO CONVEY
WHAT IT IS THAT IS IMPORTANT TO
THE PATIENT GROUP, IN TERMS OF
WHAT IS IT YOU'RE LOOKING FOR IN
A THERAPY THAT WOULD IMPACT
QUALITY OF LIFE.
WE WOULD LOVE TO FIND CURES BUT
THAT MAY NOT BE POSSIBLE BUT
THERAPIES COULD PROVIDE
SIGNIFICANT BENEFIT.
IT'S IMPORTANT TO HEAR THE
PATIENT VOICE IN THAT RIGHT FROM
THE VERY BEGINNING.
AND SO AT THE FDA, WE WANT VERY
MUCH TO HEAR WHAT THE PATIENT
PERSPECTIVE IS, AND WE HAVE
PATIENT LISTENING SESSIONS
DESIGNED SPECIFICALLY FOR THAT
PURPOSE.
WE'RE IN LISTENING MODE TO HEAR
FROM PATIENTS, FROM CAREGIVERS,
ABOUT WHAT YOUR EXPERIENCE IS,
WHAT IS IT THAT WOULD MAKE AN
IMPACT, BECAUSE ALL OF THAT
FACTORS INTO OUR THINKING AS WE
LOOK AT THE PRODUCTS THAT ARE
BEING DEVELOPED AND THE
INDICATIONS FOR THOSE PRODUCTS.
I WANT TO EMPHASIZE THE PATIENT
ENGAGEMENT IS CRITICALLY
IMPORTANT, IMPORTANT FROM DAY 1
AS PRODUCT DEVELOPMENT PLANS ARE
BEING FORMULATED.
AND WE'RE OF COURSE -- WE TRY AS
MUCH AS WE CAN TO HAVE WORKSHOPS
AND TOWN HALL MEETINGS, ET
CETERA, TO SHARE OUR CURRENT
THINKING ON DIFFERENT ISSUES AS
THEY COME UP.
THIS IS AN INCREDIBLY
FAST-MOVING FIELD.
I'VE NOT BEEN INVOLVED, YOU
KNOW, IN RESEARCH THAT HAS BEEN
MOVING AS FAST AS THE FIELD OF
GENE THERAPIES HAS BEEN MOVING.
SO WE'RE LEARNING ALONG THE WAY
TOO.
WE'RE LEARNING FROM THE
RESEARCHERS AND WE'RE LEARNING
FROM THE OUTCOMES OF TRIALS, AND
WE'RE EVOLVING IN OUR THINKING.
THAT'S WHY PUBLIC COMMUNICATION
THROUGH WORKSHOPS, TOWN HALLS,
IS SO CRITICAL.
AND WE'RE DOING THAT AS WELL IN
OUR PARTNERSHIP AND ROLE IN THE
BGTC.
I JUST WANT TO TOUCH ON ONE
THING IN PARTICULAR BECAUSE YOU
MAY HAVE HEARD THIS FROM PETER
MARX, OUR CENTER DIRECTOR,
THINKING ABOUT POTENTIAL OF
USING ACCELERATED APPROVAL
PATHWAY FOR RARE DISEASES AS A
MEANS TO GET APPROVALS AND
ACCESS FOR PATIENTS IN SOME OF
THESE THERAPIES, EARLIER IN THE
PROCESS.
ACCELERATED APPROVAL PATHWAY
DEPENDS ON DEMONSTRATION OF
SUBSTANTIAL EVIDENCE OF
EFFECTIVENESS, BASED ON THE
SURROGATE ENDPOINT OR AN
INTERMEDIATE CLINICAL ENDPOINT
THAT IS VERY LIKELY TO PREDICT
CLINICAL BENEFIT.
THIS IS SOMETHING THAT WE'RE
THINKING VERY CAREFULLY ABOUT,
AND IF THE CIRCUMSTANCES ARE
RIGHT, IF THE DATA ARE
SUPPORTIVE OF USING THIS PATHWAY
TO MOVE TOWARDS LICENSURE, THIS
IS SOMETHING THAT WE'RE
DISCUSSING AND DELIBERATING, BUT
IT'S SOMETHING TO THINK ABOUT
BECAUSE AS YOU THINK ABOUT
CLINICAL DEVELOPMENT PATHWAY
THAT YOU'RE GOING TO BE TAKING
IT'S IMPORTANT TO THINK RIGHT
FROM THE BEGINNING ABOUT WHAT
REGULATORY PATHWAY YOU'RE GOING
TO BE USING TO MOVE TOWARDS
LICENSURE, AND ENSURING SOLID
DATA TO DEMONSTRATE THIS IS AN
APPROPRIATE SURROGATE ENDPOINT
OR APPROPRIATE CLINICAL ENDPOINT
IS CRITICALLY IMPORTANT.
NATURAL HISTORY STUDIES ARE
INCREDIBLY IMPORTANT.
SO THE THINKING ABOUT -- I LIKE
TO SAY THAT -- THINK ABOUT WHAT
THE END GAME IS YOU WANT AND
WORK BACKWARDS AS YOU WORK ON
DEVELOPMENT OF YOUR CLINICAL
PATHWAYS.
AND THEN I JUST WANT TO END BY
SAYING WE'RE TALKING IN THE
BGTC, FOCUS ON DISEASES THAT
CURRENTLY HAVE NO COMMERCIAL
INTEREST.
BUT THE ENTIRE GOAL OF THIS
ACTIVITY AND THIS PROCESS AND
THIS PROGRAM IS TO REALLY GET IT
TO THE POINT WHERE DISEASES THAT
CURRENTLY DON'T HAVE COMMERCIAL
INTEREST GET TO THE POINT WHERE
THERE IS COMMERCIAL INTEREST.
THIS IS REALLY GOING TO REQUIRE
INNOVATION IN MANUFACTURING,
INNOVATION IN TECHNOLOGY, AND
REGULATORS HAVE A CRITICAL ROLE
HERE.
WE HAVE TO LOOK AT STREAMLINING
REGULATORY PATHWAYS, STILL BASED
ON SCIENCE, TO ENSURE SAFETY AND
EFFICACY.
BUT WE HAVE TO STREAMLINE THE
REGULATORY PATHWAY IN ORDER TO
HAVE PRODUCT DEVELOPERS SEE A
MEANS TO GET TO THAT ENDPOINT OF
LICENSURE FOR THERAPEUTICS
PRODUCTS FOR THESE VERY RARE
DISEASES.
THAT'S SOMETHING THAT WE ARE
LITERALLY WORKING ON EVERY DAY,
AND DECISIONS THAT WE MAKE ARE
BASED ON DATA, AND THAT'S WHY
THINGS LIKE THE BGTC AND OTHER
CONSORTIA AND CLINICAL TRIALS
ONGOING ARE SO CRITICALLY
IMPORTANT BECAUSE WE CAN LEARN
FROM THAT AS TO WHERE IS IT
APPROPRIATE TO STREAMLINE.
YOU KNOW, BECAUSE IT HAS TO BE
BASED ON DATA.
BUT THAT IS THE ULTIMATE GOAL,
THAT IS THE ONLY WAY WE'RE GOING
TO BE ABLE TO GET
COMMERCIALIZATION OF THESE
THERAPIES FOR THESE VERY RARE
DISEASES.
I WILL END AND MAYBE WE'LL TALK
ABOUT THIS LATER, BUT ESPECIALLY
IN THE RARE DISEASE SPACE IT'S
CRITICALLY IMPORTANT TO LOOK AT
PRODUCT DEVELOPMENT FROM A
GLOBAL PERSPECTIVE BECAUSE THERE
MAY NOT BE ENOUGH PATIENTS IN
ANY ONE COUNTRY.
TERRY WAS SAYING HIS SON IS THE
ONLY PERSON IN ALL OF CANADA,
THERE MAY BE ONLY 20 OR 30 IN
THE U.S., AND COMPANIES MAY NOT
WANT TO JUMP IN AND DEVELOP A
THERAPY.
IF YOU LOOK AT THE GLOBAL
POPULATION, HOWEVER, MAYBE WE
GET THAT CRITICAL NUMBER THAT
WILL HAVE, YOU KNOW, THE
MANUFACTURERS AND COMPANIES SAY
YES, WE WANT TO INVEST IN THIS
FOR DEVELOPMENT.
MAYBE WE CAN TALK MORE ABOUT THE
REGULATORY COMPONENT OF THAT
DOWN THE ROAD BUT I THINK THAT
PRODUCT MANUFACTURERS NEED TO
LOOK BROADER THAN JUST HERE OR
THERE BUT LOOK GLOBALLY FOR
THESE PRODUCT DEVELOPMENT
EFFORTS.
>> THANK YOU, GOPA.
I'LL SEGUE TO SAY WE'LL HAVE
PLENTY OF TIME FOR DISCUSSION SO
GET YOUR QUESTIONS READY AS YOU
LISTEN TO OUR CLEANUP HITTER,
DR. TRAVIS LEWIS.
>> THANK YOU.
THANKS FOR INVITING ME.
I WAS INVITED TO BE THE
CHEERLEADER FOR THIS GROUP, AS
WE TALKED ABOUT.
BUT IT'S AN EASY JOB TO HAVE
HERE.
I'M A MOVEMENTS DISORDER
NEUROLOGIST, Ph.D. WORK
STUDYING GENE THERAPY AS A
PLATFORM FOR NEURODEGENERATIVE
DISEASES WITH THIS ACT IDEA
THESE CAN BE A PLATFORM AND WAYS
TO STREAMLINE DEVELOPMENT I'M A
NEUROLOGIST WORKING IN INDUSTRY,
VARIOUS EXPERIENCES, WORKED IN
SMALL BIOTECH, CURRENTLY WORK
FOR PREVAIL THERAPEUTICS AND CAN
COMMENT ON HOW WE STARTED WITH
THE SAME ISSUES.
IT'S A DIFFICULT AND CONSTANTLY
DEVELOPING FIELD.
WITH A LOT OF DEDICATED PEOPLE.
ABOUT 2 1/2 YEARS AGO ACQUIRED
BY ELI LILLY, NOW A BIGGER
PHARMA, IT'S INSPIRING TO SEE
HOW THESE CONTINUE DEVELOPMENT
AND ADVANCEMENT OF THESE
THERAPEUTICS CAN BE PUSHED
FORWARD IN A BIG PHARMA-TYPE
SPACE, ALSO IN SMALL BIOTECH
SPACE.
I CAN SPEAK TO HOW RESOURCES AT
THE NIH, FDA, NINDS, HAVE BEEN
WORKING ON IT, EXTREMELY
IMPORTANT ACROSS REALLY EVERY
FUNCTION AS WE DEVELOP THESE
THERAPIES.
AT PREVAIL WE STUDY RARE
GENETICS FORMS, FRONTOTEMPORAL,
PARKINSON'S WITH MUTATION AND
GAUCHER'S DISEASE, A RARE AND
RAPIDLY PROGRESSING FORM OF
GAUCHER'S.
IT'S INSPIRING TO SEE, AND THESE
RESOURCES WOULD BE HELPFUL TO US
TO BE ABLE TO USE GOING FORWARD,
FOR NEW COMPANIES JOINING THAT
DON'T HAVE AS MUCH EXPERIENCE IN
THE FIELD SO THEY DON'T START
FROM ZERO BUT CAN START FROM A
RUNNING START.
IT'S REALLY INSPIRING AND
IMPORTANT AND SHOWS COMMITMENT
THESE ORGANIZATIONS HAVE TOWARDS
GENE THERAPY.
THERE'S REAL POTENTIAL HERE, IF
NOT TO CURE TO CHANGE THE
TRAJECTORY OF THE DISEASES.
I'LL ALSO COMMENT ON HOW
IMPORTANT INTERACTION WITH THE
PATIENT ADVOCACY ORGANIZATIONS
ARE FOR US.
IT'S JUST A LOT OF HARD WORK,
AND HAVING THESE INSPIRING
MOMENTS, INTERACTIONS WITH THE
FAMILIES AND PATIENTS THAT ARE
LIVING WITH THE DISEASES, THAT
WE HAVE THE OPPORTUNITY TO
SUPPORT IS REALLY MEANINGFUL.
I THINK AS WE WERE TALKING ABOUT
EARLIER TODAY, EACH INDICATION
HAS ITS OWN CHALLENGES.
AND DIFFERENT CHALLENGES, RIGHT?
DIFFERENT RATES OF PROGRESSION,
DIFFERENT POPULATIONS, DIFFERENT
NUMBERS OF PATIENTS.
SO EACH INDICATION IS UNIQUE.
SO THAT EARLY INTERACTION WITH
PATIENTS, KNOWING WHAT THEY
NEED, KNOWING WHAT WE'RE TRYING
TO DO FOR THEM, HOW WE CAN WORK
TOGETHER IS EXTREMELY IMPORTANT.
AND I CAN SPEAK FOR MYSELF, FOR
THE COMPANIES I WORKED FOR, THAT
THE PEOPLE IN INDUSTRY ARE
PASSIONATE ABOUT DOING THIS.
THESE ARE CHALLENGING.
THESE ARE SMALL DISEASES.
WE'RE DOING THIS BECAUSE WE WANT
TO SHOW GENE THERAPIES CAN
CHANGE THE COURSE OF THESE
DISEASES.
THESE ARE THE OPPORTUNITIES TO
DO THAT.
>> THANK YOU SO MUCH, DR. LEWIS.
WHAT A GREAT SEGUE INTO THE
DISCUSSION.
I'M JUST THRILLED, I KNEW I
WOULD BE, BECAUSE WE HAD A PREP
CALL.
WONDERFUL PANELISTS KNOW SO MUCH
ABOUT THE THINGS WE WANT TO KNOW
ABOUT.
WE WANT TO KNOW ESPECIALLY HOW
WE CAN HELP ADVANCE GENE
THERAPIES IN OUR VARIOUS
DISEASES.
TO OPEN THE DISCUSSION, GIVE YOU
MORE TIME TO THINK ABOUT YOUR
QUESTIONS, I PREPARED TWO
QUESTIONS OF MY OWN.
IF YOU HAVE A BURNING ONE,
INTERRUPT ME AFTER THE FIRST
ONE.
WE'LL GO TO THAT.
THE FIRST QUESTION TO KICK THIS
DISCUSSION OFF SEVERAL OF YOU
MENTIONED THIS IS DIFFICULT.
I BET EVERYBODY IN THIS ROOM,
YOU KNOW, KNOWS THAT GENE
THERAPY HAS BEEN ON OUR PLATE
FOR CLOSE TO 30 YEARS.
THE FIRST EXPERIMENTS WERE IN
THE 1990s.
AT LAST COUNT THE FDA HAS
APPROVED I THINK WE'RE UP TO 27
GENE THERAPIES.
MOST OF THOSE IN CANCER OR BLOOD
DISEASES.
ONLY ONE THAT I KNOW OF, MAYBE
TWO NOW, ARE IN NEUROLOGICAL
CONDITIONS.
SO I WILL QUOTE DR. PETER MARKS
THAT GOPA BROUGHT UP EARLIER
WHEN HE SPOKE AT ORPHAN DRUG
CONGRESS A COUPLE MONTHS AGO, HE
ITERATED WHAT WE WERE SO
HOPEFUL, GENE THERAPY IS GOING
TO BE THE CURE FOR ALL OF US,
LET'S GO.
IT'S PROVING TO BE MORE
DIFFICULT.
ISSUES ARE STILL PLAGUING
PROMISING GENE THERAPY PROGRAMS.
THERE WAS PETER, CBER DIRECTOR,
SAYING THIS IS PROVING TO BE
HARDER THAN WE HOPED.
WITH THAT IN MIND I'D LIKE TO
ASK THESE WONDERFUL PANELISTS,
FIRST OF ALL, LET ME ADD TOO IN
OUR DISEASE GROUP WE HAD ABOUT
14 DIFFERENT COMPANIES ADVANCING
GENE THERAPY AND GENE EDITING IN
OUR RARE DISEASE.
THAT NUMBER HAS DROPPED.
WE'VE HAD BIG COMPANIES ABANDON
THEIR GENE THERAPY PROGRAMS, NOT
JUST IN OUR DISEASE BUT IN OTHER
DISEASES AS WELL.
WE'VE HAD SMALLER COMPANIES
ABANDON -- WE'VE HAD OTHER
COMPANIES ABANDON, YOU KNOW, OUR
DISEASE AND ALL THEIR OTHER GENE
THERAPY PROGRAMS TO RETURN TO
SMALL MOLECULES AS A MORE VIABLE
FUTURE.
SO I'D LIKE TO ASK THE TOUGH
QUESTION OF THESE WONDERFUL
PANELISTS.
HOW HOPEFUL, HOW CONFIDENT ARE
YOU ABOUT THE FUTURE OF GENE
THERAPY FOR ALL OF OUR DISEASES
OR OTHER GENE-BASED THERAPEUTIC
APPROACHES?
>> I THINK THAT WE ARE ON THE
CUSP OF A CONVERGENCE.
I THINK THERE ARE A LOT OF
DIFFERENT AREAS, PUBLIC/PRIVATE
PARTNERSHIPS, INDIVIDUAL
DEVELOPMENT PIPELINES, RESEARCH
EFFORTS, THAT ARE EACH LOOKING
AT A SLIGHTLY DIFFERENT PIECE OF
THE PUZZLE.
SO LOOKING AT THE AAV VECTOR,
BGTC LOOKING AT THE PRE-CLINICAL
AND REGULATORY PLATFORM, AND I
THINK THAT THERE IS A TREMENDOUS
OPPORTUNITY FOR ALL OF THESE
EFFORTS TO CONVERGE AND
SYNERGIZE AND EACH ONE
ACCELERATING A LITTLE BIT OF THE
PATHWAY.
AND THEN YOU CAN BUILD MOMENTUM
FROM THE MANUFACTURING INTO THE
PRE-CLINICAL, INTO THE CLINICAL
TRIAL.
I'M PRETTY HOPEFUL.
I WAS JUST AT A CONFERENCE LAST
WEEK WITH AN ORGANIZATION CALLED
LADDERS TO CURES.
THERE HAS BEEN SUCH TREMENDOUS
WORK IN THE FIELD OF GENOME
SEQUENCING AND IDENTIFYING
INDIVIDUAL GENE ABERRATIONS FOR
THE DISEASES, ANDS WE'VE KIND OF
OF BEEN IN A TIME OF SPLITTING
THE NUANCE OF EACH INDIVIDUAL
GENE THAT HAS LED TO 7,000 AND
THEN 10,000 BECAUSE WE KEEP
FINDING SUB-SUB-SUBPOPULATIONS
OF THESE DISEASES.
WHAT THIS GROUP IS TRYING TO DO
IS LUMPING RATHER THAN SPLITTING
TO LOOK FOR COMMONALITIES, TO
LOOK FOR SHARED PATHWAYS, TO
LOOK FOR EFFORTS THAT CAN CREATE
MULTIPLE DISEASES WITH A SINGLE
TYPE OF THERAPY OR SINGLE DRUG
AND SO FORTH.
I THINK THE COMBINATION OF THIS
WORK IS REALLY PUTTING US RIGHT
ON THE CUSP OF WHAT I HOPE WILL
BE A SNOWBALL EFFORT WHERE WE
HAVE TWO OR THREE GENE THERAPIES
FOR RARE DISEASES TODAY, THAT WE
HAVE 20 IN FIVE YEARS AND 200 IN
A DECADE AND I THINK IT JUST
TAKES OFF.
>> WONDERFUL.
WHO ELSE WOULD LIKE TO
CONTRIBUTE TO THAT?
>> YEAH, I WOULD ECHO THAT.
I THINK IT'S AN EXCITING TIME.
I THINK IN THE LAST 10, 20 YEARS
WE'VE LEARNED ALL OF THE
CHALLENGES.
WE'RE STILL LEARNING MANY
CHALLENGES.
I THINK THAT THESE PLATFORM
INITIATIVES AND REGULATORY
INITIATIVES STREAMLINING THE
DEVELOPMENT ARE GOING TO GO A
LONG WAY.
THESE ARE THE HUGE HURDLES WE'VE
RUN INTO THAT TAKE A LOT OF
WORK.
YOU HAVE THE RIGHT DRUG, RIGHT
VECTOR, BUT HOW DO YOU MAKE
ENOUGH, HOW DO YOU MAKE IT IN A
WAY THAT YOU CAN USE YOUR
CLINICAL TRIAL AND PHASE 3 AND
APPROVAL.
THESE ARE -- A LOT STARTED OUT
IN RESEARCH LABS, SO BRINGING
THEM TO THE CLINIC IS A HUGE
LEAP.
AND I THINK THE SUPPORT FOR
SMALLER UPSTART BIOTECHS TO HAVE
THE RESOURCES ON HOW TO DO THIS
CORRECTLY, FROM DAY 1, I THINK
WILL STREAMLINE THE NUMBER OF
PROGRAMS OUT THERE.
AND I AGREE, WE'RE LEARNING ALL
THE OF THE HURDLES, WE'RE
LEARNING THE DIFFERENT
ADMINISTRATION AND CHALLENGES
BUT I THINK THAT WE'RE COMING TO
THAT NEXUS OF KNOWLEDGE AND
THERE'S A REALLY EXCITING
OPPORTUNITY TO MOVE FORWARD.
>> AND GOPA, COULD YOU TELL US A
LITTLE BIT ABOUT -- WE'RE
APPRECIATIVE OF THE FACT THAT
THE FDA AND CBER ARE PREPARING
FOR SUCCESS AND GROWING THEIR
RESOURCES.
I WOULD LIKE TO THANK ADVOCATES
IN THE ROOM WHO HELPED CONVINCE
CONGRESS THAT CBER NEEDED THOSE
ADDITIONAL RESOURCES TO ADVANCE
THIS FIELD.
COULD YOU TELL US ABOUT THAT
PREPARATION, THE GROWTH OF WHAT
USED TO BE THE OFFICE OF TISSUES
AND ADVANCED THERAPIES, INTO THE
SUPER OFFICE OF THE OFFICE OF
THERAPEUTIC PRODUCTS.
>> THANKS, RON.
I CANNOT THANK THE ADVOCACY
GROUPS ENOUGH BECAUSE OUR
REVIEWERS ARE AN INCREDIBLY
DEDICATED GROUP OF PEOPLE.
BUT IF YOU SEE THE NUMBER OF
APPLICATIONS THAT HAVE COME IN,
AND THIS IS JUST A REFLECTION OF
THE ADVANCEMENTS IN THE FIELD,
IT'S SIGH ROCKETED.
WE NEEDED THE RESOURCES
ABSOLUTELY.
SO, OFFICE OF TISSUES AND
ADVANCED THERAPIES HAS NOW BEEN
INCREASED INTO THE STATUS OF A
SUPER OFFICE, WHICH MEANS THAT
IT GETS MORE RESOURCES, THERE
ARE PLANS TO HIRE OVER 100 NEW
REVIEW STAFF, WHICH WILL GO A
LONG WAY TOWARDS SPEEDING UP
THINGS IN TERMS OF
COMMUNICATIONS, FEEDBACK, ET
CETERA.
I KNOW THERE'S A LOT OF -- AND
WE GO OUT THERE AND WE SAY COME
TO US, YOU KNOW, EARLY AND COME
TO US OFTEN BUT WE ALSO KNOW
THAT A NUMBER OF REQUESTS FOR
MEETINGS, WE CAN'T GIVE ALL OF
THE MEETINGS THAT ARE REQUESTED.
EVEN IF WE WANT TO.
BUT THE INCREASE IN RESOURCES,
YOU KNOW, WILL REALLY HELP A
LOT.
I DO WANT TO COMMENT ON THE
QUESTION THAT YOU ASKED ABOUT,
YOU KNOW, DO YOU FEEL OPTIMISTIC
ABOUT THE FUTURE.
I ABSOLUTELY DO.
THE REASON I DO IS BECAUSE WHAT
WE'RE SEEING HERE AROUND IN THE
BGTC AND OTHER ORGANIZATIONS IS
THE COLLABORATIVE EFFORT THAT
PEOPLE ARE PUTTING INTO DEVELOP
THESE PRODUCTS.
INDUSTRY CAN'T DO IT ALONE.
ACADEMIC RESEARCH INSTITUTIONS
CAN'T DO IT ALONE.
FDA CAN'T DO IT ALONE OF THE
PATIENT ORGANIZATIONS HAVE A
TREMENDOUS IMPACT.
BUT YOU CAN'T DO IT ALONE.
WHEN WE COME TOGETHER, AND WORK
TOGETHER, THAT'S WHERE THE
EFFICIENCIES COME IN.
AND THE REASON I FEEL OPTIMISTIC
IS BECAUSE IT MAY FEEL LIKE IT'S
MOVING SLOWLY, AND WE FEEL LIKE
IT'S MOVING SLOWLY, BUT WE ALSO
FEEL THAT IN ORDER -- YOU KNOW,
WE NEED TO DO RIGHT BY THE
PATIENT.
IF WE'RE TO APPROVE ANY
PRODUCTS, THERE HAS TO BE
DEMONSTRATION OF SAFETY AND
EFFICACY.
AND SO EFFICIENCY DOESN'T MEAN
CUTTING CORNERS.
IT SIMPLY MEANS HOW EFFECTIVELY
DO WE GET TO THAT ENDPOINT.
AND THERE ARE EFFICIENCIES THAT
CAN BE BUILT IN THROUGH
COLLABORATION, THROUGH
STREAMLINING, AND THE
STREAMLINING IS GOING TO BE
BASED ON DATA.
SO WHAT I REALLY ENCOURAGE
PATIENT GROUPS TO DO IS TO
PARTICIPATE IN NATURAL HISTORY
STUDY.
THAT DATA IS ABSOLUTELY REALLY
CRITICAL.
AND ADVOCATE TO HAVE YOUR VOICE
HEARD IN TERMS OF YOUR
VIEWPOINTS ON WHAT IS IMPORTANT
TO THE PATIENT COMMUNITY, WITH
THE PRODUCT DEVELOPERS, SO THAT
THEY UNDERSTAND WHAT IT IS
YOU'RE LOOKING FOR IN THE
PRODUCTS THAT THEY ARE
DEVELOPING.
WE FIND THESE PATIENT
ENGAGEMENTS TO BE INCREDIBLY
HELPFUL IN UNDERSTANDING WHAT IS
IMPORTANT IN TERMS OF THE FINAL
INDICATION, AND I THINK PRODUCT
DEVELOPERS WOULD BENEFIT FROM
THAT ALSO.
>> RON, COULD I ANSWER THAT?
>> GO, P.J.
>> YEAH, I'M VERY OPTIMISTIC
BECAUSE, IN PART, THE BASIC
BIOLOGY, IF YOU'RE TALKING ABOUT
MONOGENIC DISEASE WE KNOW WHAT
THE PROBLEM IS AND WHAT A
SOLUTION IS, TO GET A WORKING
COPY OF THAT MUTANT GENE INTO
THE RIGHT CELLS AT THE RIGHT
TIME OF DEVELOPMENT.
IF WE CAN DO THAT, SOMETHING
GOOD IS GOING TO HAPPEN.
THAT IS TRUE OF ALL MONOGENIC
DISEASES.
THE PROBLEM IS GETTING IT TO
THOSE CELLS THAT ENOUGH IN THE
RIGHT TIME OF DEVELOPMENT, TO
THE FIRST POINT I THINK WHAT
WE'RE SEEING, THE NERVOUS
SYSTEM, IT COMES DOWN TO
DELIVERY AGAIN AS IT ALWAYS
DOES, HOW DO YOU GET TO ENOUGH
CELLS IN THE BRAIN, THE HUMAN
BRAIN IN PARTICULAR, PARTLY WHAT
MOTIVATED US TO DO THE CHALLENGE
THAT WE'RE DOING FORT NON-VIRAL
APPROACH TO DELIVER EFFICIENTLY
GENOME EDITORS ACROSS THE
BLOOD-BRAIN BARRIER.
THE RIGHT TIME OF DEVELOPMENT OF
DISEASE IS A TRICKY ONE, TO BE
HONEST, BECAUSE RIGHT NOW WE'RE
OFTEN TRYING TO DEVELOP DISEASES
AND PARTICULARLY WHEN LOOKING AT
NEURODEGENERATIVE DISEASES FOR
PATIENTS THAT HAVE EXPERIENCED
SOME DEGENERATION.
AND IT WOULD WORK BETTER OF
COURSE IF YOU GIVE THEM THE DRUG
BEFORE THAT PROCESS STARTS.
WE'VE SEEN THAT WITH
(INDISCERNIBLE) BUT THAT RAISES
A COMPLICATED OF HOW DO WE FIND
PATIENTS BEFORE THEY ARE
SYMPTOMATIC?
AND THAT GETS INTO A LOT OF
ISSUES ABOUT NEWBORN SCREENING
WHICH I'LL NOTE BUT NOT DIVE
INTO.
IF WE WANT TO SEE THE FULL
BENEFIT AT SOME POINT WE'LL HAVE
TO THINK ABOUT THAT.
SO THOSE ARE SOME OF THE MAIN
THINGS.
THE IDEA OF THERAPEUTIC
PLATFORM, LANGUAGE IN APPROVED
LEGISLATION STARTS TALKING ABOUT
DIRECTING FDA TO START THINKING
ABOUT THERAPEUTIC PLATFORMS,
PERSONALLY I THINK A VERY BIG
STEP FORWARD BECAUSE GENE
THERAPY AND GENE EDITING, IF
THOSE ARE NOT THERAPEUTIC
PLATFORMS, I DON'T WHAT THE WORD
THERAPEUTIC PLATFORM MEANS.
THIS IDEA OF USING THOSE
THERAPEUTIC PLATFORMS TO DEVELOP
ONE TREATMENT FOR ONE DISEASE AS
A TIME DOESN'T MAKE SENSE.
IT'S A SQUARE PEG IN A ROUND
HOLE SITUATION.
WE NEED TO ADDRESS THAT.
I'M HOPEFUL THAT WE'RE GOING TO
START SEEING SOME OF THAT KIND
OF CONVERGENCE.
BASED ON THOSE PERSPECTIVES I'M
QUITE OPTIMISTIC.
>> WONDERFUL INTERVENTIONS.
THANK YOU ALL.
I'D LIKE TO GO TO MY SECOND AND
LAST QUESTION BEFORE TURNING TO
EVERYBODY HERE AND ONLINE, THIS
IS DIRECTED TO THE FACT THAT
EVERYBODY ON THE PANEL HAS
REFERRED TO THE IMPORTANCE,
ESSENTIAL IMPORTANCE, OF
ENGAGING WITH PATIENTS AND THEIR
ADVOCACY ORGANIZATIONS IN
PREPARATION FOR GENE THERAPY AND
PARTICIPATION IN GENE THERAPY.
SO MY REQUEST IS THAT WE HONE IN
ON THAT.
WE HOME IN ON THAT ESSENTIAL
NATURE.
AND TRY TO TELL THESE WONDERFUL
ADVOCATES AND THEIR PATIENTS HOW
THIS -- YOU KNOW, TERRY
CONCLUDED HIS REMARKS AFTER
TELLING US WHAT ALL HE AND HIS
FAMILY TRIED TO DO ALONG THE WAY
TO PREPARE A SUCCESSFUL PATHWAY
FOR GENE THERAPY, CONCLUDED WITH
ALL THE THINGS THEY STILL NEED
TO DO.
AND HOW IMPORTANT THEY ARE TO
THE OVERALL PROJECT.
I'D LIKE TO ASK THE PANELISTS TO
HOME IN ON THE THINGS THAT
EVERYBODY IN THIS ROOM AND
ONLINE CAN DO NOW, EVEN THOUGH
THEY ARE NOT INVOLVED IN EITHER
PGT OR BGCT TO PREPARE THEIR
COMMUNITIES AND FAMILIES TO MOVE
SMARTLY ONCE THEY DO HAVE A GENE
THERAPY PROGRAM.
>> SO WHEN WE SET OUT IN
DECEMBER OF 2021 TO START THE
PROCESS OF IDENTIFYING THE
DISEASES THAT WOULD BE IN THE
BGCT PORTFOLIO WE TURNED TO
RESEARCH AND PATIENT COMMUNITIES
TO HELP US IN THAT PROCESS.
YOU WERE INSTRUMENTAL IN GETTING
US WHERE WE ARE TODAY.
THE PRIMARY GOAL WAS TO IDENTIFY
DISEASES WHERE THE BODY OF WORK
BOTH RESEARCH CLINICAL PATIENT
ADVOCACY HAD BROUGHT SOMETHING
TO AS CLOSE TO FIRST IN HUMAN
CLINICAL TRIALS AS POSSIBLE
BECAUSE WE WANTED TO USE THESE
AS TEST CASES TO DEMONSTRATE A
PROOF OF CONCEPT THAT YOU COULD
WITHIN A SET OF MULTIPLE
DISEASES THAT INVOLVED THE SAME
ROUTE OF ADMINISTRATION, THAT
YOU COULD STANDARDIZE THE
MANUFACTURING, PRE-CLINICAL
TESTING PROTOCOL, SO FORTH, SO
WE NEEDED THINGS CLOSE TO THE
START LINE, SO TO SPEAK.
WE PUT OUT A NOMINATION FORM
BECAUSE WE WANTED THIS TO BE A
LOW BAR OF ENTRY, AND WE HAD 62
DISEASES NOMINATED.
ALMOST ALL OF THOSE HAD AN
EXTREMELY HEAVY INFLUENCE FROM
THE PATIENT ADVOCACY COMMUNITY.
WE TAKELY WERE LOOKING FOR
OPPORTUNITIES THAT ALREADY HAD
CONTACT REGISTRIES, PATIENT
GROUPS, ENDPOINT IDENTIFIED, ALL
THINGS THE PATIENT COMMUNITIES
CAN CONTRIBUTE TO.
ALL EIGHT OF THE DISEASES THAT
ENDED UP IN THE PORTFOLIO HAVE A
CONTACT REGISTRY AND ONE OR MORE
ACTIVE PATIENT GROUPS.
THIS IS GOING TO BE REALLY
INSTRUMENTAL AS WE START TO MOVE
THROUGH THE MANUFACTURING INTO
CLINICAL TESTING, REGULATORY
SUBMISSIONS, SO FORTH, THAT
WE'RE IN THE PROCESS OF
REORIENTING THE STRUCTURE OF THE
CONSORTIUM A LITTLE BIT, FOR THE
FIRST 18 MONTHS LEADING UP TO
THE SELECTION OF THE CLINICAL
PORTFOLIO WERE FUNCTIONAL
ORGANIZED WITH A TEAM AROUND
MANUFACTURING CONSIDERATIONS.
WE HAD A TEAM AROUND
PRE-CLINICAL TESTING
CONSIDERATIONS, AROUND CLINICAL
CONSIDERATIONS, EACH HAD A
DEFINED ROLE IN THE PROCESS OF
DISEASE SELECTION.
NOW THAT WE HAVE EIGHT DISEASES
WE'RE IN THE PROCESS OF FORMING
CROSS-FUNCTIONAL TEAMS, HAVING A
REPRESENT FROM MANUFACTURER,
P.I. OF CLINICAL TRIAL, BRINGING
THE VOICES OF THE PATIENT IN SO
AS WE'RE SHINING A LIGHT, AS
WE'RE GOING TO THE FDA FOR
PRE-IND MEETINGS THE PATIENT IS
THERE AT EVERY STEP OF THE WAY
ENSURING THEIR VOICE IS HEARD
EARLY AND OFTEN THROUGHOUT OUR
PROCESS.
THAT'S THE KEY THING NOW FOR
PATIENTS TO CONTRIBUTE TO,
HELPING US GET TO THAT IND
SUBMISSION AND THAT CLINICAL
TRIAL.
>> MARVELOUS.
THANK YOU.
TRAVIS?
>> I'LL ECHO HOW IMPORTANT AND
WHY.
THOSE ARE TWO MAJOR CHALLENGES,
THE DRUG DEVELOPERS STRUGGLE
WITH THE MOST.
ESPECIALLY IN RARE DISEASES,
IDENTIFYING PATIENTS, KNOWING
WHAT THE BEST ENDPOINTS ARE THAT
ARE MEANINGFUL TO THOSE PATIENTS
AND IT'S RELATIVELY EASY TO FIND
THE SCIENTIFIC LEADERS IN THE
FIELD, CLINICAL LEADERS IN THE
FIELD, SPEAK TO THEM ABOUT WHAT
THEY KNOW ABOUT THE DISEASE.
BUT HEARING FROM THE PATIENT,
HEARING WHAT END POINTS MIGHT BE
MORE RELEVANT THAN MOTOR
ENDPOINTS OR SEIZURE FREQUENCY,
THINGS ALONG THOSE LINES, MAYBE
JUST BEING ABLE TO CHANGE THEM,
TO DO THINGS THAT ARE MORE
CLINICALLY MEANINGFUL FOR THE
PATIENTS IS SO IMPORTANT.
HAVING PATIENT REGISTRIES FOR
FAMILIES SO WHEN STUDIES COME
UP, YOU KNOW YOU'LL BE ABLE TO
IDENTIFY THOSE PATIENTS.
EVEN IF IT'S ONE OR TWO, LESS
THAN TEN PATIENTS A YEAR, THEY
ARE OUT THERE.
>> WHO ELSE WOULD LIKE TO --
>> I WOULD ECHO POINTS ABOUT THE
NATURAL HISTORY STUDIES,
PARTICULARLY THE IMPORTANCE OF
HAVING CLINICAL OUTCOME MEASURES
FOR A CLINICAL TRIAL, BUT FOR
SOME OF THE GROUPS MAYBE COMING
INTO THIS, VERY KNEW, THE
IMPORTANCE OF HAVING AN ANIMAL
MODEL IS REALLY CRUCIAL AND I
THINK SOME FOLKS MAY NOT BE
AWARE THAT NOW THE DEVELOPING OF
AN ANIMAL MODEL, PARTICULARLY
MOUSE MODEL, IS A FAIRLY
STRAIGHTFORWARD THING TO DO.
YOU CAN CONTRACT WITH A COMPANY
FOR AROUND SOMETHING LIKE
$10,000 NOW, YOU CAN GET A MOUSE
MODEL MADE.
AND HERE GENOME EDITING IS JUST
A TECHNICAL TOOL, MAKES A BIG
DIFFERENCE, SO I THINK WHEN I
WAS RUNNING A RESEARCH LAB I
WORKED WITH SOME DISEASES WHERE
THERE'S ABOUT 100 PEOPLE
AFFECTED.
AND, YOU KNOW, FOR THEM RAISING
FUNDS WAS A CHALLENGE, BUT I
THINK RAISING FUNDS FOR A
SPECIFIC TARGET LIKE CAN WE
RAISE FUNDS TO GET A MOUSE MODEL
MADE, THAT'S SORT OF SPECIFIC
DELIVERABLE, IF WILL YOU, THAT
MIGHT BE A REAL BENEFIT FOR SOME
THESE DISEASES.
AGAIN, THE COST IS JUST NOT THAT
HIGH.
I WOULD ENFOURTH OF EN-- ENCOUE
WHO ARE VERY KNEW TO THINK ABOUT
THAT.
>> THANK YOU, P.J.
GOPA?
>> A QUICK COMMENT FOLLOWING UP
ON WHAT COURTNEY AND TRAVIS
SAID, WHICH I AGREE WITH
COMPLETELY, YOUR QUESTION WHAT
CAN PATIENT GROUPS DO NOW IN
PREPARATION.
WHAT IS REALLY CRITICALLY
IMPORTANT TO HAVE THE PATIENT
INPUT RIGHT THEY BEGINNING WHEN
PRODUCT DEVELOPERS ARE STARTING,
ESPECIALLY IN THE RARE DISEASE
SPACE.
YOU'RE NOT GOING TO GET TWO,
THREE TRIES AT DOING THIS.
AND SO IT'S IMPORTANT TO HAVE
YOUR VOICE HEARD SO THAT THE
DEVELOPERS ARE AWARE OF WHAT IT
IS THAT PATIENT GROUPS VIEW TO
BE IMPORTANT AND DESIGN THEIR
CLINICAL TRIALS WITH THAT IN
MIND.
THANKS.
>> THANK YOU SO MUCH.
I'D LIKE TO CONCLUDE THAT
QUESTION BY SAYING WHAT I OFTEN
SAY TO OTHER ADVOCATES.
WE'VE HEARD ABOUT WHAT WE CAN DO
NOW TO PREPARE OUR COMMUNITIES
FOR GENE THERAPY AND GENE
EDITING.
YOU'VE HEARD ABOUT CONTACT
REGISTRIES, NATURAL HISTORY
STUDIES, CLINICAL OUTCOME
MEASURES.
MY FINAL ENCOURAGEMENT IS NEVER
GET INTIMIDATED.
GET STARTED.
YOU KNOW, WE ALL STARTED ON THE
KITCHEN TABLE WITH ALL THESE
THINGS.
NOW WE'VE GOT WORLD CLASS
NATURAL HISTORY STUDIES THAT ARE
MAKING A HUGE DIFFERENCE WITH
OUR FRIENDS AT THE FDA.
WE'VE GOT CONTACT REGISTRIES
THAT ARE ENROLLING CLINICAL
TRIALS IN A MATTER OF HOURS
RATHER THAN WEEKS, MONTHS,
YEARS.
IF YOU NEED THEM DON'T BE
INTIMIDATED BY THE FINAL PRODUCT
THAT'S TAKEN US 25 YEARS TO
DEVELOP.
GET STARTED.
EVEN IF IT'S AT THE KITCHEN
TABLE.
>> RON, CAN I SAY ONE THING
ABOUT THAT?
WE HAVE NEW GROUPS COMING IN,
THEY WANT TO NOW WHAT CAN WE DO
AND HOW DO WE DO THIS, WE SAY
ASK RON BARTEK AND SEE WHAT HE
DID.
BECAUSE FARA KNOWS HOW TO DO IT,
LEARN FROM THEM.
>> YOU WERE DETERMINED TO MAKE
ME CRY, WEREN'T YOU, PJ?
>> NO, NO, IT'S TRUE.
RIGHT?
>> THANK YOU.
DIANA, DO WE HAVE ANY QUESTIONS
ONLINE?
NOT YET, OKAY.
PLEASE.
TERRY, GO.
YOU GOT THE MIC.
>> THESE ARE NOT QUESTIONS.
ONE MIGHT BE A QUESTION.
I'M GOING TO CALL A FEW THINGS
OUT.
I WANT TO ADDRESS THAT THE GENE
THERAPIES THAT HAVE BEEN MADE
TODAY, ADC DEFICIENCY, SMA,
CHERRY PICKED DISEASES, DECADES
IN THE MAKING, SHOWING AMAZING
PROGRESS.
GENE THERAPIES LIKE FOR MY SON
THAT WE'RE MAKING NOW, THESE ARE
VERY COMPLEX DISEASES.
IF WE'RE LUCKY WE'LL SLOW DOWN
THE DISEASE.
WE'RE NOT GOING TO SEE THESE
KIDS WALKING AND TALKING WHEN
THE GENERATION LIKE DR. BROOKS
SAID IS ALREADY DONE.
WE HAVE TO CATCH THESE KIDS AT 3
MONTHS, 6 MONTHS, BEFORE
MICROCEPHALY KICKS IN.
HOW DO WE DO THAT?
IF A DRUG IS IN THE CLINICAL
TRIAL, MAYBE THAT'S WHEN THE
HEEL PRICK IS THE NEWBORN
SCREENING PROGRAM IS KICKED OFF,
NOT AFTER THE DRUG IS APPROVED.
WE HAVE TO FIGURE OUT HOW TO GET
INSURANCE COMPANIES TO PAY FOR
ASOs AND GENE THERAPIES, THAT
KIND OF STUFF, WHILE THEY ARE IN
THE CLINIC, NOT AFTER THEY ARE
APPROVED.
I THINK THAT'S WHERE WE'RE GOING
TO MAKE A BIGGER IMPACT.
INSTEAD OF DOSING 10, 20, 100
PATIENTS, WE COULD DOSE
THOUSANDS AND SEE IF IT REALLY
WORKS AND MOVE THINGS FORWARD.
I KNOW THAT WE'RE SEEING AMAZING
THINGS HAPPENING BUT I THINK IF
YOU WENT TO A PARENT AND SAID I
CAN GIVE YOU FIVE YEARS OF
BETTER LIFE FOR YOUR CHILD,
THAT'S A WIN.
THAT'S A HUGE WIN.
OR MY CHILD IS ABLE TO CRAWL FOR
FIVE MORE YEARS.
OR ABLE TO GO TO BED WITHOUT
PAIN.
THESE ARE BIG WINS.
WHEN WE LOOK AT THEM, WE THINK
THEY ARE SMALL.
BUT FOR FOR A PARENT IT'S HUGE.
THESE ARE THE THINGS WE HAVE TO
THINK OF, MAYBE SMALL WINS TO
PEOPLE OUTSIDE THE COMMUNITY BUT
HUGE WINS FOR ALL OF US.
>> ABSOLUTELY.
NEXT QUESTION?
COULD EACH PERSON WITH A
QUESTION IDENTIFY THEMSELVES
FIRST.
>> HI.
CAITLIN ESPOSITO, WITH BOBBY
JONES.
AS FAR AS MANUFACTURING AND
SCALING, IS THERE ANY FUNDING
OPPORTUNITIES AVAILABLE RIGHT
NOW OR WHO IS FUNDING THOSE
INNOVATIONS?
AND IF SO, WHO IS, MORE
IMPORTANTLY, MONITORING THAT,
AND IS THAT A POTENTIAL ROLE FOR
PATIENT ADVOCACY ORGANIZATIONS,
MAYBE SOMEHOW INVOLVED IN
MONITORING OF THAT INNOVATION
AND SCALE AND MANUFACTURING
PURPOSES?
>> MAYBE GOPA AND P.J. WOULD
LIKE TO WEIGH IN.
>> YEAH, I'LL GO.
WE ACTUALLY DO FUND -- WE ARE
FUNDING ONE PROJECT TO THE SMALL
BUSINESS PROGRAM THAT AIMS TO
FIND A MORE EFFICIENT WAY TO
GROW THE CELLS TO MAKE AAV GENE
THERAPY.
SO WE ARE ABLE TO DO THAT.
I THINK THAT -- BUT GOPA ALSO --
THEY FUND WORK ALONG THOSE LINES
AT FDA TOO.
>> YES, SO THANKS FOR THE
QUESTION.
YES, THAT'S CRITICALLY
IMPORTANT.
ONE OF THE ISSUES WE HAVE RIGHT
NOW IS THAT MANUFACTURING IS A
ROAD BLOCK.
THERE JUST ISN'T THE
MANUFACTURING CAPACITY TO MAKE
AAV GENE THERAPIES, FOR EXAMPLE,
IN LARGE SCALES FOR LARGE
POPULATIONS.
IT'S A PROBLEM AT THE OTHER END
ALSO IN TERMS OF COST.
SO THE TWO APPROACHES, AND BGTC
IS FUNDING THIS ALSO AS PART OF
THEIR RESEARCH COMPONENT, WHICH
IS TO SEE MORE EFFICIENT MEANS
OF MANUFACTURING AAV GENE
THERAPIES AS WELL AS ENHANCING
GENE EXPRESSION.
WE AT FDA ALSO HAVE PUT OUT
GRANTS.
THE LAST ONE WE PUT OUT FUNDED
MAYBE FIVE OR SIX DIFFERENT
RESEARCH PROJECTS SPECIFICALLY
FOCUSED ON ENHANCING AAV GENE
THERAPIES FOR VERY SMALL
POPULATIONS, LOOKING AT
OPPORTUNITIES TO INCREASE
EFFICIENCY OF THE MANUFACTURING.
YOU RAISE THE POINT I JUST
WANTED TO TAKE THE OPPORTUNITY
TO TOUCH ON WHEN YOU THINK ABOUT
PRODUCT DEVELOPMENT WHICH IS
THERE'S A LOT OF FOCUS ON
CLINICAL DEVELOPMENT.
THERE SHOULD BE.
BUT USUALLY WHAT ENDS UP BEING A
PROBLEM AT THE END OF THE DAY IS
MANUFACTURING, IN TERMS OF
PRODUCT APPROVAL.
SO, AGAIN, THAT'S SOMETHING ONE
NEEDS TO BE FORWARD THINKING ON.
IF YOU'RE DOING SMALL SCALE
MANUFACTURING FOR EARLY PHASE
CLINICAL TRIALS, HOW ARE YOU
GOING TO SCALE UP AND DO THE
COMPARABILITY, IF YOUR PATIENT
POPULATION IS ONLY TEN PEOPLE
MAYBE THERE'S SOME MEANS TO DO A
BATCH SUCH THAT YOU DO THE
PRE-CLINICAL TESTING AS WELL AS
THE CLINICAL TESTING USING THE
SAME BATCH.
YOU HAVE TO THINK ABOUT -- COST
FACTOR COMMENTS IN BUT I THINK
IN THE RARE DISEASE SPACE
THINKING AHEAD WHERE DO YOU WANT
TO END UP, AND THEN WORK
BACKWARDS TO SEE WHAT YOU NEED
TO DO TO GET THERE MOST
EFFICIENTLY IS IMPORTANT.
>> I WANT TO ADD ONE OTHER
THING.
GOPA TOUCHED ON THE RESEARCH THE
BGTC IS FUNDING WHICH WE HOPE
WILL EVENTUALLY LEAD TO
IMPROVEMENTS IN THE
MANUFACTURING PROCESS.
ONE OTHER SPACE TO WATCH, THERE
IS A MANUFACTURING USA
INSTITUTE, NATIONAL INSTITUTE
FOR INNOVATION MANUFACTURING
BIOPHARMACEUTICALS, NIMBLE WITH
TWO Is.
THEY ARE FUNDED BY THE NATIONAL
INSTITUTE OF STANDARDS AND
TECHNOLOGY WHICH WHERE I WAS
BEFORE I CAME TO THE FOUNDATION,
A FULL CIRCLE CONNECTION THERE.
AS PART OF THE CONTRIBUTION TO
BGTC, THEY ARE DOING A VERY
LARGE AMOUNT OF IN-KIND
RESEARCH, $6 MILLION OF EFFORT
TOWARDS AN OPEN SOURCE
MANUFACTURING PLATFORM FOR GENE
THERAPIES.
THAT'S SOMETHING PROCEEDING
ALONGSIDE THE BGTC, BASED ON THE
TIMING OF THE WORK, WASN'T
SOMETHING WE COULD INCORPORATE
INTO OUR MANUFACTURING
PRE-CLINICAL TESTING BUT COULD
POTENTIALLY FORM THE BASIS OF A
FUTURE ITERATION OF A
CONSORTIUM, ALL THE AMP PROGRAMS
THAT STARTED IN 2014 HAVE SINCE
CONTINUED ON OR EXPANDED INTO
LARGER PROGRAMS OR BROADER
PROGRAMS.
I THINK THERE'S GOING TO BE A
LOT OF EXPECTATION THE BGTC WILL
DO SO ALSO.
SO OVER THE NEXT TWO TO THREE
YEARS NIMBLE WILL BE PUTTING OUT
PROTOCOLS, VARIOUS RESEARCH
RESOURCES, REFERENCE MATERIALS
AND STANDARDS THAT WILL ALSO
REALLY HELP MOVE TOWARDS THAT
PLATFORM AND MANUFACTURING
PROCESS.
>> RON, I CAN FOLLOW UP WITH ONE
MORE POINT, THAT THE QUESTION
ABOUT MANUFACTURING FOR GENE
THERAPIES CAN BE QUITE DIFFERENT
THAN GENE EDITING.
FOR GENE THERAPY, USING AAV, YOU
NEED TO KEEP -- TO GET AAV IN
THE CELL TO KEEP MAKING THE
THERAPY TO PROTEIN.
FOR GENE EDITING IT'S ACTUALLY
QUITE THE OPPOSITE.
YOU NEED TO GET A GENOME EDITOR
TO CORRECT THE MUTATION BUT ONCE
THAT'S DONE YOU WOULD RATHER
HAVE IT GO AWAY.
THAT'S ONE OF THE THINGS WE'RE
EXCITED ABOUT IN THE GENOME
EDITING PROGRAM IS TO SEE IF WE
CAN ADAPT THE SAME TECHNOLOGY
USED IN THE COVID VACCINES AND
ADAPT THAT FOR THE DELIVERY OF
GENOME EDITORS.
SO WE'LL CALL IT A SIMPLE
NANOPARTICLE, NOT SIMPLE TO
CROSS THE BLOOD-BRAIN BARRIER,
BUT THAT'S THE IDEA, A QUITE
DIFFERENT CHALLENGING FOR GENOME
EDITING AND GENE THERAPY.
SPEAKING FROM NCATS WE'RE TRYING
TO PLAY BOTH SIDES OF THE STREET
HERE.
BECAUSE I THINK WE WANT AS MANY
SHOTS ON GOAL AS POSSIBLE.
>> I WOULD LIKE TO ADD TO THIS
DISCUSSION OF MANUFACTURING,
GOPA, YOU MENTIONED EARLIER DR.
PETER MARX, ONE OF THE TRUE
LEADERS IN THIS FIELD, TRYING O
INCREASE EFFICIENCY AND REDUCE
COST OF MANUFACTURING, THE
LONGEST POLE IN THE TENT.
IT MAKES GENE THERAPIES SO
OUTRAGEOUSLY -- I SHOULDN'T SAY
OUTRAGEOUSLY EXPENSIVE BUT IT'S
A KEY PLAYER.
COURTNEY MENTIONED NIIMBLE.
TWO YEARS AGO THEY HELD THEIR
ANNUAL SUMMIT, PETER MARKS AND
P.J. AND I SPOKE ABOUT THE
IMPORTANCE OF INCREASING
EFFICIENCY, REDUCING COST,
MANUFACTURING, TWO YEARS AGO,
AND IN THIS ROOM WE HAD AN NCATS
WORKSHOP ON MANUFACTURING WHICH
THE NCATS DIRECTOR AND PETER
MARKS CHAIRED THE DISCUSSION, WE
HAD INDUSTRY PARTNERS, ACADEMIC
INVESTIGATORS, ADVOCATES
DISCUSSING THIS ISSUE.
WE'VE COME A LONG WAY.
WE'VE GOT A LONG WAY TO GO.
I THINK DIANA HAS A QUESTION.
>> THANKS, RON.
I HAVE A COMMENT FROM HEIDI
WALLIS, BUT IT MIGHT PROMPT
DISCUSSION OF ADVOCACY IN THIS
AREA.
IN ADDITION TO ASKING INSURANCE
TO COVER EXPENSIVE DRUGS, WE
NEED TO CONQUER GET NEWBORN
SCREENING PAID FOR.
SO MANY STATES ARE UNDERFUNDED
IN THIS CRITICAL PROGRAM.
>> WHO WOULD LIKE TO TAKE
NEWBORN SCREENING ON?
>> I MEAN, I THINK THERE'S
CERTAINLY MANY, MANY CHALLENGES
THERE.
I DO THINK THAT IT RELATES TO --
I SAY NEWBORN SCREENING, LET ME
BACK UP AND SAY THIS IS MY
PERSONAL OPINION HERE.
I DO THINK THAT THE NEWBORN
SCREENING FIELD NEEDS TO TAKE
INTO ACCOUNT THE FACT THAT WE'RE
STARTING TO DEVELOP GENE TARGET
THERAPIES AS THERAPEUTIC
PLATFORMS, WHAT AS CURRENTLY
NEWBORN SCREENING IS ONE DISEASE
AT A TIME, ANOTHER EXAMPLE OF
THE SQUARE PEG IN THE ROUND HOLE
SITUATION.
A COUPLE YEARS AGO WE HAD A
SERIES OF MEETINGS SPONSORED BY
NCATS TO TRY TO DEAL WITH THAT
LACK OF CONVERGENCE.
AND I THINK THAT REMAINS A
PROBLEM.
I'M GOING TO PUT INTO THE CHAT
SOME INFORMATION ABOUT THOSE
SERIES OF MEETINGS.
I WOULD AGREE, I THINK THERE'S A
MAJOR NEED FOR REEVALUATION OF
THE WAY WE DO NEWBORN SCREENING
IN LIGHT OF THE WAY WE'RE
DEVELOPING GENETIC THERAPIES
NOW, NOT JUST GENE THERAPY AND
GENE EDITING BUT
OLIGONUCLEOTIDES, THE SPEAK YOU
CAN DEVELOP A THERAPEUTIC FOR A
DISEASE NOW IS VASTLY DIFFERENT
THAN WHEN THE NEWBORN SCREENING
LEGISLATION WAS WRITTEN I THINK
IN THE 1980s AND THERE HAS TO
BE A CONSIDERATION OF THAT.
>> I'LL PILE ONTO THAT, P.J.,
AND SAY FOR MANY OF US IN THE
ADVOCACY COMMUNITY, WE SEE THE
CRYING NEED FOR EARLIER
IDENTIFICATION.
TERRY MENTIONED IT IN HIS
DISEASE.
EARLIER IDENTIFICATION OF OUR
PATIENTS BECAUSE BY THE TIME
THEY ARE CLINICAL MANIFEST,
WHICH IS THE ONLY ALTERNATIVE TO
IDENTIFICATION OUTSIDE NEWBORN
SCREENING, SO MUCH OF THE DAMAGE
MIGHT HAVE BEEN DONE THAT IT'S
THAT MUCH MORE DIFFICULT, MAYBE
EVEN IMPOSSIBLE TO REVERSE.
SO I AGREE WE NEED TO REVISIT
THE WHOLE CONCEPT OF NEWBORN
SCREENING, AND I KNOW IT'S BEING
DONE, BUT CURRENTLY YOU NOT ONLY
HAVE TO HAVE A TREATMENT THAT'S
FOR THAT DISEASE BUT YOU HAVE TO
HAVE A TREATMENT THAT'S BEEN
DEMONSTRATED TO BE NECESSARY TO
BE APPLIED TO INFANTS.
AND SO THAT'S A HIGH HURDLE.
UNTIL WE GET THERE, WE STILL
NEED TO IDENTIFY PATIENTS EARLY
ENOUGH TO MAKE A PROFOUND
BENEFIT TO THEM.
WHAT OTHER -- ANY OTHER
COMMENTS?
>> YEAH, I WANT TO ADD ONE
COMMENT TO THAT.
ASIDE FROM THE BENEFIT OF
SCREENING TOWARDS THERAPEUTIC
TREATMENT OPTIONS, I THINK THERE
MAYBE NEEDS A RECOGNITION OF THE
BENEFIT TO THE CAREGIVER AND THE
FAMILY.
I THINK STATISTICS ARE THAT IT
TAKES AN AVERAGE OF SEVEN YEARS
TO HAVE A RARE DISEASE DIAGNOSIS
CORRECTLY.
THAT PATIENTS TYPICALLY UNDERGO
MULTIPLE INCORRECT DIAGNOSES
ALONG THAT JOURNEY.
SO EVEN JUST KNOWING, NOT HAVING
TO GO THROUGH THAT PROCESS OF
FALSE DIAGNOSES AND TIME AND
UNCERTAINTY, I THINK IS A
BENEFIT TO THE FAMILY AND TO THE
PATIENT AND TO THEIR CAREGIVER.
ABSENT ANY OTHER TREATMENT
OPPORTUNITY.
>> YEAH, I AGREE WITH THAT
COMPLETELY, COURTNEY.
>> JUST ONE QUICK COMMENT AND
ADDED PERSPECTIVE.
FIRSTLY, IF YOU CAN PREVENT
SUFFERING, THEN YOU DO IT.
BUT FROM A PRODUCT DEVELOPMENT
SCIENTIFIC POINT OF VIEW, IF YOU
KNOW WHAT THE DISEASE
MANIFESTATION IS, YOU KNOW WHAT
HAPPENS TO PATIENTS WHO HAVE A
PARTICULAR DISEASE.
IF YOU CAN CATCH IT EARLY BEFORE
ANY OF THE MANIFESTATION STARTS
WHEN DO YOU THERAPEUTIC
TREATMENTS THE ENDPOINT IS
CLEAR.
YOU KNOW WITHOUT ANY
INTERVENTION YOU KNOW WHAT THE
OUTCOME WOULD BE.
IF YOU CAN INTERVENE BEFORE THE
SYMPTOMS START, THEN WHETHER OR
NOT THAT PRODUCT IS WORKING AS A
THERAPY WILL BECOME MUCH CLEARER
THAN IF DISEASE PROGRESSION HAS
ALREADY STARTED, AND YOU'RE JUST
LOOKING FOR INCREMENTAL BENEFIT.
THAT'S WHERE WE GET INTO
DIFFICULTY IN DETERMINING
WHETHER OR NOT A THERAPY IS
EFFECTIVE WHEN YOU'RE LOOKING
FOR INCREMENTAL CLINICAL BENEFIT
AS OPPOSED TO SOMETHING CLEAR
CUT.
YOU INTERVENE EARLY, YOU DON'T
END UP WITH DISEASE SYMPTOMS.
VERSUS DISEASE SYMPTOMS HAVE
STARTED, NOW YOU'RE LOOKING TO
SEE IF THERAPY IS SLOWING THINGS
DOWN OR BRINGING INCREMENTAL
BENEFIT.
SO THAT'S ANOTHER REASON TO
START EARLY.
>> TERRIFIC POINT.
TERRIFIC POINT.
>> CAN I ADD?
>> TRAVIS HAS ONE MORE COMMENT.
>> A QUICK COMMENT FROM THE
DEVELOPER SIDE, IT'S REALLY --
OBVIOUSLY WE'RE NOT SURPRISED
YOU AGREE WITH THAT STATEMENT,
RIGHT?
BUT I THINK FIRST-IN-HUMAN
TRIALS WHERE THE RISK IS
COMPLETELY UNKNOWN, WHERE DO YOU
START AT FIRST PATIENT DOSING?
AND SO TREATING PATIENTS
PRESYMPTOMATICALLY WE'RE
INTERESTED IN DOING, THE BEST
WAY TO DO IT, BUT NEED TO BE
ABLE TO SHOW, FIRST AND
FOREMOST, THE PRIORITY, HAVING
DIALOGUES HOW TO BALANCE THOSE
CONFLICTING CHALLENGES IS REALLY
IMPORTANT.
WE'RE ON THE SAME TEAM.
>> WHAT A WONDERFUL MOMENT.
ADVOCATES PARTICIPATE IN THE
PROCESS OF CLARIFYING FDA
GUIDANCE WITH INDUSTRY PARTNERS
IN THE ROOM BECAUSE I THINK
THERE'S STILL SOME
MISUNDERSTANDING AND
MISINTERPRETATION OF GUIDANCE
THAT'S ON THE STREET.
AND I THINK ANY EFFORTS WE CAN
HELP FOSTER TO GET INDUSTRY
PARTNERS TOGETHER WITH THE FDA
AND MAKE SURE WE'RE ALL ON THE
SAME PAGE, VARIOUS CATEGORIES
LIKE PEDIATRIC RESEARCH THAT
WE'LL TALK ABOUT LATER, AND I
THINK IN WHICH THAT'S REALLY
IMPORTANT.
WE HAVE A QUESTION UP TOP.
>> MY NAME IS MARIA, WITH CURE
MLD.
MY QUESTION IS FOR P.J. NOW THAT
HE'S OPENED UP THAT PANDOR'S A
BOX OF NEWBORN SCREENING.
>> HI, MARIA.
>> HI, P.J.
ONE OF THE THINGS I THOUGHT
ABOUT IS GIVEN THE FACT THAT WE
CAN'T WAIT 30 YEARS FOR ACH AND
-- NO, ACH DNC TO GIVE APPROVAL
AND DO LOBBYING IN 50 STATES, DO
WE TAKE IT OUT OF THE HANDS OF
THE GOVERNMENT AND PUT IT IN THE
PATIENT'S HANDS IN TERMS OF
ASKING FOR HOLE GENOME
SEQUENCING AT BIRTH FOR
TREATABLE AND HERITABLE
DISEASES, EXACERBATING HEALTH
INEQUITIES IN THE SYSTEM BUT
THAT'S LIKELY BEGINNING TO
HAPPEN, WHERE FAMILIES WHO HAVE
RESOURCES WILL JUST DO WHOLE
GENOME SEQUENCING AT BIRTH AND
SAY, LISTEN, I'M NOT GOING TO
WAIT FOR NORTH DAKOTA TO DO
THIS, AND I'M GOING TO THROW
THAT OUT TO YOU AND THEN THE
SECOND PART IS AS YOU PIONEER
THIS NEW ERA OF GENE THERAPY,
THERE HAS TO BE A TWIN
REVOLUTION IN DIAGNOSTIC
MEDICINE WITH NEUROLOGISTS
LEADING THE WAY AND BASICALLY
GETTING PEDIATRICIANS TO STOP
THINKING I NEED TO WAIT FOR THE
KID TO GET SICK TO DIAGNOSE, AND
LET'S WAIT AND SIGH, AS OPPOSED
TO LET'S USE WHOLE GENOME
SEQUENCING THE MINUTE I HAVE A
KID IN THE ICU OR EVEN I SEE LOW
TONE.
I DON'T KNOW WHAT THE ANSWER IS
HERE BUT THERE HAS TO BE A TWIN
EDUCATIONAL EFFORT FOR FRONTLINE
PCP PEOPLE TO GET READY FOR GENE
THERAPY BECAUSE THEY ARE NOT
DIAGNOSING OUR KIDS IN TIME.
THAT'S MY QUESTION.
SORRY, P.J.
>> OH, SURE.
NO, IT'S A GREAT QUESTION MARIA,
AND YOU KNOW THIS ISSUE BETTER
THAN ANYBODY.
I THINK WE ARE FUNDING SOME WORK
AND THERE'S BEEN SOME PAPERS
PUBLISHED RECENTLY FROM WORK
FUNDED BY THE CTSA PROGRAM,
STEPHEN KINGSMORE AND
COLLEAGUES, SHOWING THE BENEFIT
OF WHOLE GENOME SEQUENCING FOR
PATIENTS IN THE ICU AND THEY
HAVE BEEN DEMONSTRATING THE
FINANCIAL IMPACT OF THAT, THAT'S
SOMETHING THAT'S QUITE
IMPORTANT.
I CAN PUT SOME LINKS IN THE CHAT
FOR THAT.
BUT I THINK THERE'S AN EVEN MUCH
BROADER PROBLEM WHICH IS WHAT
ABOUT FINDING KIDS WHO AREN'T
SYMPTOMATIC AT ALL YET BUT WILL
BE IN A COUPLE YEARS, AND I
THINK WE'VE ALL SEEN THE STORY
OF NILA AND THE DEVELOPMENT, IN
THE COURSE OF A YEAR, AND I LOOK
AT THAT AND THINK WHAT WOULD
HAVE HAPPENED IF THEY DIAGNOSED
NILA AS A NEWBORN.
SHE HAD NO SYMPTOMS AS A
NEWBORN.
IF WE DON'T HAVE A MUCH BROADER
NEWBORN SCREENING WE'RE GOING TO
PRIMARILY BE LOOKING AT PEOPLE
SYMPTOMATIC, THAT'S A
FUNDAMENTAL PROBLEM.
THE SOLUTION LIES BEYOND NIH,
BUT THAT'S WHY WE HAD THAT
SERIES OF MEETINGS AND I PUT THE
LINK IN THE CHAT TO RAISE THIS
ISSUE BECAUSE HOW YOU CHANGE
THAT, AS I SAID THAT GOES BEYOND
NIH TO A DIFFERENT PART OF THE
GOVERNMENT, I THINK THERE'S A
NEED FOR REAL CREATIVE SOLUTIONS
THERE, LET ME JUST PUT IT THAT
WAY.
>> I WAS VERY ENCOURAGED TO HEAR
ABOUT A PROGRAM THAT IS TRAINING
OB/GYNs IN ISSUES OF GENETIC
SCREENING.
THEY MADE THE POINT THAT
FREQUENTLY THROUGH THE IVF
PROCESS GENETIC SCREENING AND
COUNSELORS ARE BUILT INTO THE
PROCESS BUT NOBODY BUILDS INTO
THE NORMAL OBSTETRIC PROCESS.
HAVE THAT CONVERSATION WITH YOUR
OB PRIOR TO DELIVERY ABOUT
GENETIC SCREENING AND TESTING TO
HAVE GENETIC COUNSELORS AS PART
OF THE OB TEAM CAN GO A LONG WAY
TOWARDS THAT.
>> PENNY HAS A QUESTION.
>> ASSOCIATION FOR
FRONTOTEMPORAL DEGENERATION,
REPRESENTING ADULT SIDE.
SOME CAUSES ARE AUTOSOMAL
DOMINANT, ONE OF THE THINGS THT
WE PUT FORWARD IS WE DON'T
RECOMMEND GENETIC TESTING FOR
EVERYBODY BECAUSE THERE ARE
RAMIFICATIONS OF INSURANCE,
RAMIFICATIONS FOR JUST DO YOU
WANT TO KNOW WHAT'S IN YOUR
FUTURE?
BUT AT THE SAME TIME WE HAVE
HARD ACCESS TO GENETIC
COUNSELORS, YOU GOT DIAGNOSED
BUT IT MAY NOT BE CAUSED BY A
GENETIC VARIANT.
MOST PEOPLE CAN'T ACCESS THE
COUNSELORS, USUALLY WITHOUT
EXPERTISE IN THAT FORM OF
NEURODEGENERATION, SIMILARITIES
AND DIFFERENCES, THE EARLIER WE
STOP, THE EARLIER WE TREAT, THE
BETTER WE'LL BE ABLE TO HELP
PEOPLE BEFORE THE BRAIN HAS
GOTTEN DAMAGED, BUT THERE'S SOME
PROFOUND DIFFERENCES IN TERMS OF
WHO GETS TO DECIDE IF AND WHEN
YOU GO THROUGH THAT TESTING, AND
WHAT ARE THE RESOURCES THAT ARE
OUT THERE TO HELP THE PEOPLE AND
FAMILIES MAKE INFORMED DECISIONS
FOR THEMSELVES?
JUST A GENERAL COMMENT FOR
ANYONE TO RESPOND TO.
>> WELL SAID.
I THINK IT'S CERTAINLY A
CHALLENGE WITHIN THAT
POPULATION.
ONE OF THE BIGGEST PROBLEMS, THE
NEUROLOGISTS ARE NOT OFFERING
WITH CLEAR EXPLANATION HOW TO
THINK ABOUT IT.
PARKINSON'S DISEASE,
FRONTOTEMPORAL DEMENTIA, WITH
DISEASE-MODIFYING THINGS OUT
THERE, PATIENTS SHOULD BE MADE
AWARE IF YOU ARE HAVE A GENETIC
SUBTYPE THERE MAY BE A CLINICAL
TRIAL OR EVENTUALLY A THERAPY
YOU CAN TAKE.
BUT THE ONLY WAY TO KNOW IF IT'S
RIGHT FOR YOU IF YOU GET GENETIC
TESTING AND EXPLAIN WHAT THAT
ENTAILS.
EACH STATE HAS THEIR OWN
CHALLENGES.
EACH STATE HAS DIFFERENT
CHALLENGES, EXPERT CENTERS
AVAILABLE, WHERE THESE PEOPLE
ARE BEING DIAGNOSED.
I THINK THAT'S THE FIRST HURDLE,
JUST FOR THE CLINICIAN TO BE
AWARE THAT THESE POTENTIAL
THERAPIES ARE OUT THERE, THAT
EVEN JUST THE GENETIC UNDERLYING
OF THE DISEASE IS A REAL
POSSIBILITY.
AND THEN EXPLAINING IT IN A
CLEAR WAY TO THE PATIENT TO MAKE
THEIR INFORMED DECISION, I
TOTALLY AGREE CLINICIANS DON'T
HAVE TIME OR EXPERTISE TO DO THE
COUNSELING IN THE WHICH YOU WANT
IT DONE.
SO WE REALLY -- THOSE EXPERT
CENTERS WITH GENETIC COUNSELORS
ARE AN AMAZING RESOURCE BUT
HAVING ACCESS TO COUNSELING IN
GENERAL IS REALLY IMPORTANT.
THERE'S REALLY INTERESTING
SCREENING PROGRAMS OUT THERE IN
THE PARKINSON'S DISEASE, THE
PARKINSON'S FOUNDATION SPONSORS
INCLUDING GENETIC TESTING AND
COUNSELING, VIRTUALLY AS WELL,
THAT HAS TO BE BUILT IN AND I
TOTALLY AGREE.
>> ARE THERE ANY FINAL QUESTIONS
FROM ANYONE IN THE ROOM OR
ONLINE?
HEARING NO TAKERS, WE CAN GIVE
YOU BACK A LITTLE BIT OF YOUR
MORNING TO PREPARE FOR LUNCH,
AND I WOULD LIKE YOU TO JOIN ME
IN THANKING THIS TERRIFIC PANEL.
[APPLAUSE]
>> WE'LL TURN IT OVER TO JILL
MORRIS, PROGRAM DIRECTOR,
DIVISION OF NEUROSCIENCE.
>> HI, EVERYONE.
TODAY WE'LL TALK ABOUT THE
ETHICS AND CHALLENGES IN GENE
THERAPY, I THINK THIS WILL BE A
VERY LIVELY DISCUSSION.
SO, I AM AN NINDS PROGRAM
DIRECTOR, I DID MY THESIS WORK
IN A GENE THERAPY LAB BACK IN
THE EARLY 1990s.
I WAS TELLING MARIA, I TRAINED
WITH PAUL ORCHARD, WHO DOES MANY
BONE MARROW TRANSPLANTS FOR GENE
THERAPY.
I'M RESPONSIBLE FOR MULTI-RARE
AND ULTRA RARE NEUROLOGICAL
DISORDERS THAT ARE CURRENTLY
USING GENE THERAPY.
I'M A MEMBER OF THE BESPOKE TEAM
AND ALSO NINDS LEAD FOR THE RARE
DISEASE CLINICAL RESEARCH
NETWORK FOR THE RDCRN THROUGH
NCATS.
WHICH ALLOWS TO ESTABLISH
CLINICAL TRIAL READINESS FOR
RARE AND ULTRA RARE DISEASES,
AND NINDS SUPPORTS 11 OF THE 20
CONSORTIUM THAT ARE FUNDED
THROUGH THE RDCRN.
WE'RE GOING TO BEGIN, I'LL HAVE
EACH OF THE SPEAKERS INTRODUCE
THEMSELVES, AND THEN I WANT THEM
TO ANSWER THIS ONE QUESTION,
DURING THEIR INTRODUCTION, WHAT
DO YOU THINK ARE THE CURRENT
SIGNIFICANT CHALLENGES AND
ETHICAL CONCERNS FOR GENE
THERAPY?
WHY DON'T WE START WITH REGHAN.
>> THANK YOU, I'M REGHAN FOLEY,
PEDIATRIC NEUROLOGIST,
NEUROMUSCULAR SPECIALIST, SENIOR
RESEARCH PHYSICIAN AT THE NINDS.
A LOT OF OUR WORK IS NATURAL
HISTORY WORK AND CLINICAL TRIAL
READINESS, LOOKING FOR
BIOMARKERS.
WE'VE HAD A FEW GENE THERAPY
STUDIES, MANY IN THE PIPELINE SO
WE DID AN INTRATHECAL AAV9 AND
SYSTEMIC WITH AAV8, THEY HAVE
BEEN VERY EDUCATIONAL
EXPERIENCES.
FOR ME, ETHICAL CONCERNS IN THE
GENE THERAPY FIELD, THERE IS
REASON FOR OPTIMISM, ALSO REASON
TO STRETCH AND HOLD THE FIELD TO
A HIGHER STANDARD OF
TRANSPARENCY BETWEEN THE
SPONSOR, ACADEMIC OR INDUSTRY,
TRANSPARENCY IS ABOUT THE
CONSTRUCT, ABOUT THE GENE
THERAPY ITSELF.
MAKING SURE INVESTIGATORS ARE
AWARE PRE-CLINICAL DATA THINGS
TO LOOK OUT FOR TRANSPARENCY, N
REAL TIME AS ADVERSE EVENTS
BECOME APPARENT.
IT'S IMPERATIVE TO BE AWARE OF
WHAT'S GOING ON AT OTHER SITES
IN REAL TEAM.
IF THAT DOESN'T HAPPEN WE CAN'T
OPTIMIZE THE SAFETY FOR THE
PATIENTS ENROLLED AS WELL AS
MITIGATE RISK FOR FUTURE
PATIENTS.
BUT ALSO THE WORD COMES TO MIND
RESPONSIBILITY.
AS A FIELD TO MAKE GENE THERAPY
MORE AVAILABLE BUT ALSO
RESPONSIBILITY TO BE RESPONSIVE
TO THE PATIENTS AND FAMILIES.
SO, THAT RESPONSIVENESS, WHAT'S
NECESSARY AND IMPORTANT FOR
OUTCOME MEASURES, BUT ALSO
RECOGNIZING PATIENTS AND THEIR
FAMILIES ARE THE TRUE EXPERTS,
THEY NEVER CHOSE TO BE EXPERTS
IN RARE DISEASES, WE SHOWS TO BE
EXPERTS BUT THEY LIVE THEY.
LIVED EXPERIENCE HAS TO BE
RESPONDED TO, WE HAVE TO BE
RESPONSIBLE TO FAMILIES WHILE
WE'RE LAUNCHING AND DURING AND
ADVERSE EVENTS, WE HAVE
RESPONSIBILITY TO QUICKLY AND
TRANSPARENTLY REPORT EXACTLY
WHAT HAPPENED.
EVERYONE NEEDS TO KNOW EXACTLY
WHAT HAPPENED.
>> I'M A PATIENT ADVOCATE FOR
GENE THERAPY, AN ACCIDENTAL
ADVOCATE.
SINCE I WAS 12 MY YOUNGEST
DAUGHTER WAS DIAGNOSED WITH
LEUKODYSTROPHY, WE WERE AT THE
CHILDREN'S HOSPITAL AT
PHILADELPHIA WITH ONE OF THE
BEST NEUROLOGY TEAMS IN THE
WORLD, AND ON THE FIFTH JULY A
YOUNG DOCTOR TOLD MY MY DAUGHTER
HAD MLD, BASICALLY ALS AND
ALZHEIMER'S IN A 2-YEAR-OLD.
THEY PRESENT AT BIRTH COMPLETELY
NORMAL AND HEALTHY.
MY DAUGHTER HAD INHERITED THE
DISORDER, INHERITED TWO FAULTY
COPIES OF THE GENE WHICH MADE IT
IMPOSSIBLE FOR HER BODY TO PRO
PRODUCE A SINGLE PROTEIN.
THE DEFICIENCY OF THE PROTEIN
WAS CAUSING SULFOTIDES TO
ACCUMULATE IN HER BRAIN,
BASICALLY KILLING TEAR SLOWLY.
AS A YOUNG DOCTOR WHO JUST
FINISHED RESIDENCY AND
FELLOWSHIP EXPLAINED TO ME ABOUT
MLD, AND MY HUSBAND HELD OUR
LITTLE GIRL IN HIS ARMS I HADN'T
SPOKEN IN ABOUT A WEEK SINCE WE
HAD FIRST GONE TO THE HOSPITAL
AND WE WAS DIAGNOSED, 5th JULY
DIAGNOSIS CONFIRMED, HADN'T
SPOKEN IN A WEEK AND THEN
COULDN'T SHUT UP.
I UNDERSTAND MY DAUGHTER IS
DYING.
SHE SHOWED ME THE MRI, THE
DAMAGE TO THE BRAIN WAS SO
CATASTROPHIC, YOU COULD SEE THE
BRAIN RECEDING FROM THE SKULL.
AND I UNDERSTOOD MY DAUGHTER
WOULD NEVER BE SAVED, A DEAD
NEURON IS A DEAD NEURON.
BUT I SAID TO HER, WILL YOU EVER
HAVE A TREATMENT?
SHE SAID YES.
THERE'S A THING CALLED GENE
THERAPY.
I SAID TO DR. WALDMANN, I DON'T
KNOW WHAT EVER POSSESSED ME TO
SAY THIS, I SAID, WHEN YOU FIND
THIS GENE THERAPY, WHEN YOU MAKE
IT WORK, I WANT YOU TO FIND ME.
I DON'T KNOW HOW OLD I'LL BE.
I DON'T KNOW WHERE I WILL BE.
BUT I WANT YOU TO FIND ME AND
GET ME ON A PLANE TO ICELAND OR
PARIS OR WHEREVER YOU FIND THIS
BABY, THAT YOU CAN GIVE GENE
THERAPY TO, AND I WANT TO MEET
HER AND HER MOTHER.
IN I'M REALLY LUCKY, MAY BE
SHE'LL HAVE BROWN EYES AND CURLY
BROWN HAIR LIKE MY LITTLE GIRL.
AND DR. WALDMAN HUGGED ME AND
SAID I'M SO SORRY.
A YEAR LATER, THIS IS ABSOLUTELY
TRUE, YOU CAN CHECK, A YEAR
LATER A YOUNG RESEARCHER NAMED
AL SANDRA BIFFI PUBLISHED IN THE
JOURNAL OF SCIENCE, SHE TREATED
SUCCESSFULLY THREE CHILDREN WITH
THIS.
I CALLED DR. WALDMANN, I WAS NOT
HAPPY.
I WAS PRETTY PISSED OFF.
I SAID, AMY, WHAT THE HECK?
YOU SAID 10, 20 YEARS.
ONE YEAR AFTER CAL'S DIAGNOSIS?
MARIA, THERE WAS NEVER ANY WAY
TO SAVE CAL.
WE'VE NEVER SAVED, BY THE TIME
THEY SHOW SYMPTOMS IT IS OUT OF
CONTROL.
YOU NEVER COULD HAVE SAVED CAL.
THESE FAMILIES IN DR. BIFFI'S
TRIAL PAID AN INCREDIBLE PRICE,
SACRIFICED ONE CHILD TO THE
DISEASE TO SAVE THE YOUNGER ONE.
SHE SAID YOU MUST HELP THEM.
I WAS STARTING A FOUNDATION,
SELLING CUPCAKES.
I DON'T KNOW WHY.
I NEEDED TO DO SOMETHING.
I WAS GOING TO GIVE THE MONEY TO
PALLIATIVE CARE, TO CHOP.
A LITTLE-KNOWN FACT.
I WAS RAISING MONEY FOR
PALLIATIVE CARE BECAUSE THAT'S
ALL THEY COULD DO FOR MY
DAUGHTER.
DR. WALDMAN SAID GIVE IT TO THE
GENE THERAPY FAMILIES, GET THEM
TO ITALY.
AND A YEAR LATER, THE FIRST
AMERICAN CHILD NEEDED TO GET TO
ITALY.
2014.
AND FOUND THEM ON FACEBOOK, AND
THEY FOUND ME.
FOR THE LAST TEN YEARS THAT'S
WHAT I HAVE DONE.
I HAVE SENT 27 CHILDREN TO
TREATMENT IN ITALY AND NOW IN
THE UNITED STATES WITH THE
AMAZING PAUL ORCHARD.
AND MY DREAM WHEN MY DAUGHTER
WAS GOING TO DIE HAS COME TRUE.
I CAN NOW SIT IN A ROOM FULL OF
CHILDREN WHO CAN SING AND DANCE
AND HAVE NO AWARENESS OF THE
FACT THAT THEY HAVE MLD.
MY DAUGHTER GRANTED ME A
FRONT-ROW SEAT TO THE BIGGEST
MEDICAL BREAKTHROUGH IN A
GENERATION.
SO, I NOW WORK WITH A COMPANY
CALLED ORCHARD THERAPEUTICS.
IN THE NEXT YEAR I CAN TELL YOU
WITH CERTAINTY THAT THAT GENE
THERAPY WILL BECOME A
COMMERCIALLY AVAILABLE THERAPY
IN THE UNITED STATES.
WE'RE NOW WORKING TO MAKE SURE
THAT EVERY CHILD IN THE UNITED
STATES IS SCREENED FOR THIS
DISORDER.
THIS HAS BEEN AN AMAZING JOURNEY
TO BE IN THE FIRST GENERATION OF
GENE THERAPIES.
IT IS SAFE.
IT IS DURABLE.
IT GETS ME TO THE CHALLENGE.
I'M SORRY I'M GOING A LITTLE
LONG.
IT'S A LONG STORY.
I DON'T HAVE ANY SCIENTIFIC
CREDENTIALS, MY Ph.D. IS IN
SOCIOLOGY, MY FATHER WOULD SAY
YOU FLUNKED CHEMISTRY TWICE, THE
FACT THAT YOU'RE AT THE NIH IS A
MIRACLE IN ITSELF.
THAT ANYONE IS LISTENING TO
ANYTHING YOU HAVE TO SAY GIVEN
YOU COULD NOT MASTER CHEMISTRY
IS AMUSING.
I PROBABLY HAVE MET MORE GENE
THERAPY PATIENTS THAN NEARLY
ANYONE IN THE WORLD.
THE FIRST CHALLENGE IS MONEY.
IN 2018 I PUBLISHED A PIECE IN
STAT I SAID THE SCIENCE OF GENE
THERAPY IS NOT AS HARD AS THE
MATH OF PAYING FOR IT.
AND WE WILL FACE SERIOUS
PROBLEMS IN TERMS OF
REIMBURSEMENT.
I HAD THE GREAT HONOR OF HELPING
GET APPROVAL IN GERMANY AT THE
NHS, THAT WAS EASY COMPARED TO
WHAT WE'LL BE FACING HERE.
IT'S A VERY SOLVABLE PROBLEM BUT
THERE'S NO POLITICAL WILL TO
SOLVE THE PROBLEM OF PRICE OF
GENE THERAPY, END OF STORY.
WE COULD TALK ABOUT THAT.
IT'S NOT THE NIH'S
RESPONSIBILITY FOR THE FDA'S
RESPONSIBILITY, IT'S CONGRESS'
RESPONSIBILITY.
WE CAN GET CONTROVERSIAL LATER.
CHALLENGE TWO, THE ROLE FOR
INDUSTRY.
I AM NOT SURE THAT PROFIT FOR
COMPANIES IS A GREAT MODEL FOR
GUARANTEEING BREAKTHROUGHS IN
GENE THERAPY GIVEN SO MANY
MONOGENICS ARE RARE DISEASES,
AND I LOSE SLEEP EVERY SINGLE
NIGHT WONDERING, BECAUSE IF WE
CAN'T GET THIS SUSTAINABLE, I
DON'T THINK ANY OF US ARE.
WE HAVE NEARLY FAILED MANY, MANY
TIMES FOR REASONS THAT HAVE
NOTHING TO DO WITH THE SCIENCE.
I DON'T KNOW IF INVESTORS AND
STOCKHOLDERS ARE NECESSARILY THE
BEST PARTNERS LONG TERM FOR OUR
SPACE.
THAT'S AN OPEN QUESTION.
I DON'T KNOW THE ANSWER BUT I'M
NOT SURE.
I THINK BESPOKE IS AN INCREDIBLE
IMPORTANT INNOVATION, I'M NOT
SURE IF BUSINESS SIDE OF THINGS
IS GOING TO BE SUSTAINABLE LONG
TERM.
CHALLENGE NUMBER THREE, I
MENTIONED THIS EARLIER, GENE
THERAPY REQUIRES A RADICAL
DIAGNOSTIC PARADIGM SHIFT IN
WHICH DOCTORS TREAT CHILDREN WHO
LOOK PERFECTLY HEALTHY.
IMAGINE WE HAVE NOW TREATED
THREE PRESYMPTOMATIC CHILDREN IN
THE LAST YEAR WITH COMMERCIALLY
APPROVED DRUG IN ENGLAND AND
GERMANY.
WE'VE ASKED THE BRITISH PEOPLE
AND GERMAN PEOPLE TO SPEND, I
DON'T KNOW HOW MUCH, MILLIONS OF
EUROS ON A BABY THAT LOOKS
PERFECTLY FINE.
THAT IS A HUGE LIFT.
HOW DO WE KNOW THIS BABY IS
GOING TO GET SICK ONE DAY?
AND SO THOSE CHALLENGES ARE
REALLY SERIOUS.
AND GETTING PRACTITIONERS IN THE
FIELD TO ABANDON A STYLE OF
MEDICINE THEY HAVE PRACTICED FOR
THOUSANDS OF YEARS TO IDENTIFY A
CHILD FROM A SYMPTOM
PRESENTATION CLINICALLY IS GOING
TO BE A HUGE CHALLENGE WHICH I
THINK THE NIH AS MUCH AS I
RESPECT P.J., I THINK THE NIH
SHOULD BE TRAINING AND TALKING
TO THE APA AND AMA ABOUT THE
TOOLS OF GENOMIC MEDICINE.
CHALLENGE FOUR, WHAT THE HECK
DOES GENE THERAPY EVEN DO?
THAT'S NOT A SILLY QUESTION.
WE DON'T KNOW WHAT IT DOES,
HONESTLY.
IT'S BEEN TEN YEARS SINCE THE
FIRST CHILDREN WERE TREATED IN
MY CLIME CLINICAL TRIAL.
THEY ARE WALKING AROUND, MILD
NEUROPATHY, SOME USE BRACES,
SOME DO NOT.
SOME HAVE VERY HIGH I.Q.s,
SOME MORE AVERAGE OR BELOW
NORMAL.
THEY ARE BEAUTIFUL AND AMAZING.
HOWEVER, WHAT IF THIS THERAPY IS
USED ON SYMPTOMATIC CHILDREN WHO
GET 20 YEARS IN A WHEELCHAIR?
WHAT IF IT'S USED ON PEOPLE AND
WE'VE OWN GIVEN THEM A MILDER
VERSION OF THE DISEASE AND ONE
DAY THEY GET SICK?
IN ONCOLOGY WORLD FIVE YEARS
DISEASE FREE IS A CURE.
IN RARE DISEASE SPACE THAT'S NOT
TRUE.
I NEVER USE THE C WORD, WHICH IS
CURE.
I'M MAKING A JOKE.
I CAN'T USE THE C WORD.
BUT THE CANCER COMMUNITY DOES
FOR CAR T CELL, WHICH IS ANOTHER
ISSUE I THINK WE CAN DISCUSS.
AND I THINK I WILL LEAVE IT
THERE.
OH, ONE LAST CHALLENGE.
THE THING THAT HAUNTS ME MOST OF
ALL IS THAT OF ALL THE CHILDREN
I GOT TO ITALY, THERE WAS ONLY
ONE CHILD I COULD NOT GET TO
ITALY.
A YOUNG AFRICAN AMERICAN MOTHER
AND HER BABY OUT OF RURAL NORTH
CAROLINA.
THIS IS GOING TO BE A HUGE
MEDICAL JUSTICE ISSUE.
AND THIS DISEASE, MLD, HAS A
HIGH INCIDENCE IN THE NAVAJO
NATION, AND THE ALASKA TRIBAL
NATION.
I HAVE NEVER SEEN A CHILD
REFERRED FROM A TRIBAL HEALTH
CARE SYSTEM.
WE CAN'T EVEN GET IN THERE.
RIGHT NOW THE NAVAJO NATION SHUT
DOWN ALL GENETIC TESTING AND
RESEARCH.
I DON'T KNOW HOW WE'LL EVER GET
IN.
THESE CHALLENGES ARE WHAT KEEP
ME UP AT NIGHT.
AND NOW I PASS IT OFF TO DOUBLE
DOWN AND MAKE THINGS MORE
INTERESTING.
>> GOOD AFTERNOON.
I SHOULD START BY SAYING HOW
INCREDIBLY HUMBLED I AM TO BE
HERE AND HAVE THE OPPORTUNITY TO
LISTEN TO FAMILY STORIES,
PATIENT STORIES, AND I THINK
THIS IS SUCH AN INCREDIBLE FORUM
WHERE MAYBE I DON'T SPEAK JUST
ON MYSELF, WE DON'T ALWAYS GET
IN A ROOM AND CAN HEAR DIRECTLY
ABOUT THOSE EXPERIENCES, SO I'M
VASILIKI RAHIMZADEH, GREEK AND
IRANIAN, GRADE SCHOOL WAS FUN.
YOU HAVE A FULL RANGE OF
PROFESSIONS, THE JOKE, YOU CAN
BE A DOCTOR, LAWYER, OR
ENGINEER.
SO, AMONG THE THREE OF US, SEEMS
WE'RE ALL IN THE MEDICAL
PROFESSION, PROBABLY NOT BY
COINCIDENCE.
MY ROLE AS A FACULTY MEMBER AT
BAYLOR COLLEGE OF MEDICINE, IN
THE CENTER FOR MEDICAL ETHICS
AND HEALTH POLICY, A LOT OF MY
RESEARCH CENTERS ON ETHICAL,
LEGAL, SOCIAL ISSUES OF EMERGING
GENETIC TECHNOLOGIES WITH
SPECIAL FOCUS ON CHILDREN.
AND I SPEND MUCH OF MY EARLY
CAREER FOCUSED ON SOME OF THE
DATA GOVERNANCE AND PRIVACY
ISSUES AND SHARING GENOMIC AND
ASSOCIATE DATA WITH CHILDREN,
THE RARE DISEASE COMMUNITY IS
OFTEN A POSTER CHILD, A POSTER
DISEASE NETWORK IN WHICH GENOMIC
DATA SHARING IS NOT ONLY
ADVANCING SCIENTIFIC DISCOVERY
BUT OFTEN WHERE INFORMATION AND
DATA ARE ACTUALLY THE TREATMENT
BECAUSE OF ITS RARITY, BECAUSE
OF THE SMALL N AND THE NEED,
SCIENTIFIC NEED TO IDENTIFY
PATIENTS WITH SIMILAR CLINICAL
AND GENOTYPE -- PHENOTYPE AND
GENOTYPE TO LINK THEM TOGETHER
TO DEVELOP AND FIND AND ENHANCE
DATA DISCOVERY ACROSS THESE
DIFFERENT CASES TO EXPAND KIND
OF THE EVIDENCE BASE.
AND SO THIS COMMUNITY NOT ONLY
BEING A SCIENTIFIC IMPERATIVE TO
DO THAT, THERE ARE ETHICAL
CONSEQUENCES TO A LOT OF THE
SCIENCE WE'RE TALKING ABOUT
TODAY.
SO I THOUGHT IT WOULD BE HELPFUL
TO OPEN UP, WE STARTED A
CONVERSATION ABOUT NEWBORN
SCREENING, THIS IS AN AREA IN
WHICH THERE'S BEEN DEBATE AND
CONTROVERSY, MOSTLY ON ETHICS,
TO INTEGRATING WHOLE GENOME AND
EXOME SEQUENCING AT THE NEWBORN
SCREENING LEVEL.
I THOUGHT I WOULD ANIMATE SOME
OF THAT DISCUSSION AS PROMISED.
AND SO THE FIRST -- I'LL TRY TO
MAYBE LANDSCAPE SOME OF THE
ETHICAL DEBATE ON BOTH SIDES.
THE FIRST IS THAT, YOU KNOW,
PUBLIC HEALTH SCREENING PROGRAMS
LIKE NEWBORN SCREENING IS MEANT
TO -- IT HAS THIS POPULATION
HEALTH FOCUS.
AND IT IS SOMEWHAT ANTAGONISTIC
TO THE WHOLE GENOME AND EXOME
SEQUENCING MANTRA, WHICH IS VERY
MUCH PRECISION MEDICINE, VERY
MUCH PERSONALIZED.
AND WHEN WE LOOK ACROSS PLACES,
EVEN WITHIN THIS COUNTRY,
NEWBORN SCREENING IS
DIFFERENTIALLY APPLIED.
IT'S DIFFERENTIALLY COVERED.
IT'S DIFFERENTIALLY EFFECTIVE.
AND THIS IS VERY MUCH AT THE
GOVERNMENT AND STATE RESOURCING
LEVEL THAT'S HAVING SUCH
DIFFERENT OUTCOMES, KIND OF AT
THE GROUND LEVEL.
WHEN WE SCALE TO INTERNATIONAL
CONTEXT, IT'S RATHER ABYSMAL.
AMONG THE PUBLIC HEALTH
COMMUNITY AND PUBLIC HEALTH
GENOMICS PROFESSIONALS ARE
PASSIONATE ABOUT ENSURING BASIC
NEWBORN SCREENING THAT'S
AVAILABLE ACROSS ALL POPULATIONS
FOR EVERY BABY, EVERYWHERE, AND
THIS HAS NOT HISTORICALLY BEEN
ACHIEVED TO DATE.
SO ADDING IN REALLY EXPENSIVE,
VERY HIGH RESOURCE, BOTH HUMAN
AND MATERIAL RESOURCE
INTENSIVENESS TO THE NEWBORN
SCREENING PROCESS IS GOING TO
EXACERBATE THESE ISSUES WE KNOW
CONTINUE TODAY.
SO YOU HEAR AND ARE FACED WITH
PATIENTS AND FAMILIES FOR WHOM
WHOLE GENOME AND EXOME
SEQUENCING MADE AN INCREDIBLE
IMPACT ON DIAGNOSTIC YIELD, ON
ENDING THE DIAGNOSTIC ODYSSEY
FOR MANY PATIENTS AND FAMILIES
AND VERY DIFFICULT TO ARGUE
THAT, YOU KNOW, THAT ACCESS
WASN'T A DIRECT CONSEQUENCE,
THAT DIAGNOSTIC -- THAT
DIAGNOSIS ITSELF, ACCURATE
DIAGNOSIS, WASN'T A DIRECT
CONSEQUENCE OF SEQUENCING AND I
THINK THAT'S SUCH A PASSIONATE
APPEAL FOR PATIENTS AND FAMILIES
AND WHAT'S REALLY DRIVING THE
CONVERSATION FOR AT LEAST
STUDYING IMPLEMENTATION AT
NEWBORN SCREENING LEVEL.
WE KNOW FOR OTHER CONDITIONS
THERE ARE MANY FOR WHICH WE HAVE
A LOT OF DATA TO SUGGEST THE
CLINICAL ASSOCIATION AND GENETIC
AND GENOMIC ETIOLOGY OF DISEASE.
THERE ARE LOTS WE KNOW VERY
LITTLE ABOUT, CONTINUOUSLY
CHANGING.
THERE'S PROBABLY MORE VARIANTS
OF UNKNOWN SIGNIFICANCE THAN
THOSE VARIANTS OF KNOWN
SIGNIFICANCE.
AND THIS HAS IMPORTANT
IMPLICATIONS FOR CLINICAL
DECISION MAKING, WHEN WE'RE
FACED WITH A FAMILY WHO HAS TO
DECIDE TREATMENT A, TREATMENT B,
TREATMENT C, AND THIS VARIANT
WE'VE DISCOVERED IS EITHER
BENIGN TODAY OR UNKNOWN TODAY,
AND THAT HAS CHANGES.
THERE'S BEEN A LOT OF DISCUSSION
IN THE CLINICAL AND
BIOINFORMATICS COMMUNITY ABOUT
HOW WE ACTUALLY MERGE RESEARCH
DATA AND EMERGING, YOU KNOW,
SCIENTIFIC DATA INTO THE
CLINICAL REALM AND SOME OF OUR
EXISTING DATA INFRASTRUCTURES
DON'T ALLOW FOR THAT.
SO THERE IS A WHOLE ECOSYSTEM,
UPDATING THAT DOESN'T CURRENTLY
HAPPEN, THAT HAS VERY IMPORTANT
IMPLICATIONS FOR DECISIONS AT
THE BEDSIDE.
SO THESE ARE JUST SOME ARGUMENTS
FOR AND AGAINST, AND AT THE
MOMENT ONE OF THE MOST IMPORTANT
EXPERIMENTS, I'LL CALL IT, PILOT
TESTING THAT'S REALLY HAPPENING,
IS THROUGH THE NATIONAL HEALTH
SERVICE IN THE UNITED KINGDOM
PILOTING WHOLE GENOME SEQUENCING
WITHIN THEIR POPULATION AND IT
HAS BUILT IN AN EVALUATION
STUDY, A LONG-TERM OUTCOME STUDY
TO SEE WHEN WE DO THIS AT A
POPULATION LEVEL AND GETTING THE
NUMBERS WE NEED AND FOR OTHER
COUNTRIES TO REALLY FOLLOW SUIT
AND GET DATA ON HOW DOES THIS --
HOW IS THIS OPERATIONALIZED IN A
POPULATION LEVEL, WHAT IS THE,
YOU KNOW, AT THE POINT OF CARE
WHAT ARE THE IMPACTS TO CLINICAL
DECISIONMAKING, AND THEN AT
LEAST WITH, YOU KNOW, A LOT OF
IMPORTANCE AND TIMELINESS AND
SENSITIVITY, IN THIS COUNTRY,
THE IMPACTS ON REPRODUCTIVE
DECISION MAKING.
WE'RE LIVING IN A POST-ROWE ERA,
OVERNIGHT A LOT OF THESE
REPRODUCTIVE DECISIONS THAT WERE
AVAILABLE JUST A YEAR AGO ARE
NOT TODAY.
AND I THINK THAT ADDS ANOTHER
LAYER OF ETHICAL COMPLEXITY TO
SOME OF THESE NEWBORN SCREENING
DECISIONS.
I COULD TALK AT LENGTH AND I'LL
END A LITTLE BIT WITH SOME
ISSUES AND DATA THAT I'M FOCUSED
ON, SO THERE ARE A FIELD OF
ETHICS AND PEDIATRIC
BIOETHICISTS CONCERNED ABOUT
FUTURE PRIVACY OF CHILDREN.
AS WE'RE ADVOCATING FOR OPEN
DATA TRANSPARENCY IN THE DATA,
MERGING DATASETS TOGETHER, WE'RE
INTERESTED WHAT EFFECT THAT WILL
HAVE BOTH HARMFUL AND BENEFICIAL
TO CHILDREN AS THEY GET OLDER,
WILL THEY MAKE THE SAME DATA
DECISIONS AND DATA SHARING
DECISIONS AS THEIR PARENTS?
AND WILL THEY HAVE THIS CONCEPT
CALLED A RIGHT TO OPEN FUTURE,
RIGHT TO A PRIVATE FUTURE, IN
MAKING SOME OF THOSE DECISIONS
ONCE THEY REACH THE AGE OF
MAJORITY.
THOSE ARE SOME ETHICAL AND
PHILOSOPHICAL THINGS I'VE BEEN
FOCUSED ON IN MY WORK.
>> THANK YOU.
I HAVE A COUPLE QUESTIONS AND
WE'LL BE TAKING QUESTIONS FROM
THE AUDIENCE.
STARTING WITH REGHAN, HOW DO YOU
ENSURE TRULY INFORMED CONSENT,
RISKS ASSOCIATED WITH GENE
THERAPY, CLINICAL TRIALS?
>> FOR ME, THIS IS A VERY
IMPORTANT TOPIC.
AS A CLINICIAN, A PHYSICIAN,
WE'RE THE ONES WHO ARE OBTAINING
CONSENT FROM FAMILIES AND
PARENTS PRIOR TO GENE THERAPY
DELIVERY.
I THINK IT'S ESSENTIAL, TO BE
TRULY INFORMED THE PHYSICIAN HAS
TO BE REALLY AWARE IN REAL TIME
OF ALL THE ADVERSE EVENTS WITH
THE GENE THERAPY PRODUCT AROUND
THE WORLD.
IF THE PHYSICIAN IS NOT AWARE OF
ALL THE EVENTS AT THE TIME OF
CONSENT, IT'S NOT TRULY INFORMED
CONSENT.
GOING BACK TO TRANSPARENCY WITH
SPONSORS, INVESTIGATORS, ALL
INVESTIGATORS NEED A FORUM TO
SHARE IN REAL TIME WHAT THEY ARE
SEEING BECAUSE THEY ARE USUALLY
THE EXPERTS IN THAT RARE DISEASE
AND THE SPONSOR MAY NOT BE AS
EXPERT OR ALARMED, BUT THE
FINDING WOULD BE ALARMING TO THE
PHYSICIAN.
IT INCLUDES HONEST DISCUSSION
ABOUT FAMILIES ABOUT WHAT IS
KNOWN IN THE STUDY SO FAR AS
WELL AS UNKNOWNS, INCLUDING
DEATH.
IT IS ONLY HUMAN NATURE, IT'S O
BE EXPECTED SUBCONSCIOUSLY
EXPECT A POSITIVE OUTCOMES, AND
THEY ARE THE ONES THAT ARE
REJECT THE AS BEING THE OUTCOME
EVERYONE IS SEEING BUT NOT EVERY
OUTCOME IS POSITIVE THE FAMILY
HAS TO UNDERSTAND ONE POSSIBLE
OUTCOME COULD BE DEATH.
AND THAT WOULD BE ABSOLUTELY
ESSENTIAL THAT FAMILY
UNDERSTANDS THAT AND STATES THAT
BEFORE THEY SIGN THE CONSENT
FORM.
FOR ME, TRULY INFORMED CONSENT
IS REALLY ESSENTIAL PROCESS,
WHAT'S KNOWN TO DATE,
RECOGNIZING SOMETIMES GENE
THERAPY CAN RESULT IN DEATH.
WE'VE SEEN THAT FIRST HAND, IT'S
VERY IMPORTANT, THIS DELICATE
DISCUSSION, ALSO ONGOING
DISCUSSION TO BE -- TO OCCUR
EVEN THE NIGHT BEFORE AND THE
DAY OF THE GENE THERAPY, DO YOU
STILL WANT TO PROCEED, DO YOU
UNDERSTAND POTENTIALLY THIS MAY
RESULT IN THE DEATH OF YOUR
CHILD, ARE YOU OKAY WITH THAT
RISK?
>> DOES ANYBODY ELSE HAVE
ANYTHING TO ADD?
>> I THINK, YOU KNOW, THE
TOLERANCE FOR RISK IS SO VARIED
AND HAVE YOU FAMILIES WHO AS
TERRY TALKED ABOUT SELL THEIR
HOUSES OR REFINANCE THEIR HOMES,
SO THERE'S A GREAT DEAL AT STAKE
IN TERMS OF -- I'VE SEEN
FAMILIES SELL THEIR BELONGINGS
AND GET ON A PLANE, SIGHT
UNSEEN, JUST SHOW UP AT A
CLINICIAN'S DOOR.
WE'RE NOT TERRIBLY GOOD AT
MAKING RATIONAL DECISIONS BUT I
DO THINK IT'S QUITE IMPORTANT.
AT THE SAME TIME, I WAS REALLY
IMPRESSED BY A RECENT PIECE IN
THE NEW YORKER ABOUT PROVIDING
THERAPY TO PEOPLE WHO ARE DYING.
MY PERSPECTIVE AS PATIENT
ADVOCATE IN NEUROLOGY SPACE IS
THAT SWING FOR THE FENCES BUT I
UNDERSTAND LEGITIMATE CONCERNS,
BUT I DEAL WITH FAMILIES MAKING
THIS CHOICE I TELL THEM TWO
THINGS.
ONE, IT'S A CLINICAL TRIAL.
YOU DON'T HAVE TO DO THIS.
YOU'RE NOT ABANDONING YOUR CHILD
IF YOU DO NOT DO WHAT TERRY DID
AND START A COMPANY AND YOU
DON'T HAVE TO DO THIS.
THE SECOND THING I SAY TO THEM
IS THAT YOU NEED TO BE ABLE TO
LIVE WITH WHATEVER DECISION YOU
MAKE.
WHATEVER YOU'RE CHOOSING NOW FOR
YOUR FAMILY, YOUR CHILD, YOU
NEED TO BE ABLE TO LOOK BACK AND
SAY I'M AT PEACE WITH THAT
DECISION.
THAT'S MY TWO CENTS FROM THE
PATIENT PERSPECTIVE.
>> I'LL BUILD A LITTLE BIT.
THIS PHENOMENON AND OBSERVATION
WE'RE MAKING ABOUT OFTEN SEEING
CLINICAL CARE AND RESEARCH BE
ONE AND THE SAME, PARTICULARLY
IN POPULATIONS WHERE THERE
AREN'T THERAPEUTIC OR
FDA-APPROVED THERAPIES, AND
CURATIVE OPTIONS, THIS IDEA OF
THERAPEUTIC MISCONCEPTION.
SO WHEN ESPECIALLY PATIENTS AND
FAMILIES ARE ENROLLING IN
CLINICAL TRIALS, THIS IS NOT
UNIQUE TO GENE THERAPY, YOU HAVE
FAMILIES THAT ARE REALLY AT THE
END OF THEIR ROPE, AT THE END
OF -- HAVE EXHAUSTED OTHER
OPTIONS.
THERE IS THIS VERY PASSIONATE
APPEAL TO WHATEVER IS BEING
PROVIDED IN THE CLINICAL TRIAL
AND ACCESS TO THE CLINICAL TRIAL
AS A MEANS OF A CURE OR AT LEAST
WILL GET YOU ON THE PATH TO
CLINICAL CARE.
SO WE -- THERE'S A LOT OF
ETHICAL DEBATE ABOUT THIS
CONCEPT OF THERAPEUTIC
MISCONCEPTION THAT HAS DIRECT
IMPACT ON THE INTEGRITY OF THE
INFORMED CONSENT PROCESS.
AGAIN EMPHASIZING DIFFERENCES
BETWEEN CLINICAL CARE AND
RESEARCH.
RESEARCH IS MEANT TO IDENTIFY
AND GENERATE NEW KNOWLEDGE ABOUT
CERTAIN BIOLOGICS AND
INTERVENTIONS.
AND YOU CAN IMAGINE THE TIMING
OF THAT CONVERSATION HAVING ALL
OF THE -- MAKING ALL OF THE
DIFFERENCE.
SO, ADDRESSING ISSUES OF
THERAPEUTIC MISCONCEPTION,
TIMING OF DISCUSSION, ANDS
SOMETIMES A LESSER KNOWN ASPECT
OF THE INFORMED CONSENT PROCESS
IS THAT IT'S NOT A ONE-TIME ONE,
YOU KNOW, DECISION TIME POINT.
IT SHOULD BE AN ONGOING PROCESS
AT DIFFERENT PARTS OF THE
PROCESS, SO INITIAL DISCUSSIONS
ABOUT WHAT ARE POSSIBLE TRIALS,
A FAMILY MIGHT BE ELIGIBLE FOR,
ACTUAL CONSULTATION PROCESS THE
DAY BEFORE IT HAPPENS, THIS IS A
DEMONSTRATION OF ONGOING AND
DYNAMIC CONSENT, WHICH WE HAVE
FOUND IN SOME STUDY ALLOWS FOR
RIGOROUS AND INFORMED CONSENT
PROCESS.
ONE OF THE OTHER MAJOR ISSUES
THAT WE'RE FACING IS THE
DIVERSIFICATION WITHIN DATASETS
AND WHO IS GETTING ACCESS TO
CLINICAL TRIALS SO WE'RE NOT
ABLE TO SAY MEANINGFUL CLINICAL
AND ACTIONABLE RESULTS FROM
CLINICAL TRIALS IF WE DON'T HAVE
A DIVERSE PATIENT POPULATION
ENROLLED IN THOSE TRIALS IN THE
FIRST PLACE.
THE INFORMED CONSENT PROCESS IS
OFTEN THE TIME POINT AT WHICH
MANY ELIGIBLE FAMILIES DON'T
FOLLOW THROUGH AND WE KNOW THIS
BECAUSE THERE ARE -- THERE'S
ABJECT -- SOMETIMES MISTRUST OF
THE HEALTH CARE SYSTEM, EVEN
MORE MISTRUST OF THE RESEARCH
ENTERPRISE, SO IT WAS MENTIONED
EARLIER INDIGENOUS AND NATIVE
COMMUNITIES ARE AT THE TOP OF
THE LIST DIRECTLY HARMED BY
RESEARCH IN THE PASS.
THERE'S A CULTURAL COMPETENCY
THAT HAS TO BE EMBEDDED IN THE
INFORMED CONSENT PROCESS, VERY
PATIENT AND FAMILY SPECIFIC,
REQUIRES A LOT MORE THAN SIMPLY
UNDERSTANDING THE RISK.
UNDERSTANDING AND COMMUNICATING
RISKS AND BENEFITS OF THE
INTERVENTIONS.
>> I WANTED TO SEE IF WE HAVE
QUESTIONS FROM THE AUDIENCE.
>> WORRY TALKING ABOUT INFORMED
CONSENT -- WE'RE TALKING ABOUT
INFORMED CONSENT.
MANY OF YOU KNOW I WORK IN THE
RARE DISEASE SPACE.
A CHALLENGE THAT I SEE, WE
AREN'T TO A CLINICAL TRIAL YET
BUT I'VE OBSERVED MANY PATIENT
GROUPS THAT GO THROUGH THIS
BECAUSE FAMILIES ARE SO
DESPERATE, ESPECIALLY IN THE
RARE DISEASE SPACE, LOOKING FOR
A TREATMENT.
I FIND A GAP BEFORE INFORMED
CONSENT OF GETTING AN EDUCATION
OR BASIC SIMPLE MESSAGE OUT TO
INCLUSION AND EXCLUSION CRITERIA
BECAUSE WHAT I'M SEEING, EVEN
TRYING TO EDUCATE OUR OWN
COMMUNITY IS UNDERSTANDING THAT
NOT EVERYONE WILL BE ABLE TO
PARTICIPATE.
THEN THAT INADVERTENTLY CAUSES A
DIVISION WITHIN THE GROUP
ITSELF.
I DON'T KNOW MANY THAT HAD THIS
HAPPEN BUT I SEE THERE'S A GAP.
THIS IS THE TEACHER COMING OUT
IN ME.
HOW DO WE EDUCATE THESE FAMILIES
IN A GINGER WAY, BECAUSE THIS IS
ALL HIGHLY SENSITIVE.
WE ALL WANT TREATMENT.
BUT HOW DO WE COME ACROSS BEFORE
WE GET TO THE INFORMED CONSENT
EDUCATING THE PATIENT COMMUNITY
ON HOW WE GET TO EVEN AN
INFORMED CONSENT FOR THESE
THINGS AND UNDERSTANDING THE
RISKS.
DOES THAT MAKE SENSE?
>> THIS IS REALLY HARD.
THIS IS THE HARDEST THING I DO.
A COUPLE MONTHS AGO ACTUALLY A
MOTHER CALLED ME AND SAID I WANT
TO START A LETTER-WRITING
CAMPAIGN TO A COMPANY TO PUT
PRESSURE ON THEM TO OPEN A
CLINICAL TRIAL.
AND SHE WANTED ME TO HELP HER
LEVERAGE FUNDING FOR THIS.
SHE'S VERY PASSIONATE AND
DESPERATE AND I SAID -- SHE HAD
A CHILD WITH ADVANCED MLD.
IT WAS CLEAR SHE THOUGHT IF SHE
DID THIS THE CHILD WOULD BE IN
THE TRIAL.
I WENT RIGHT IN BECAUSE THAT'S
HOW I AM.
I SAID THIS IS ALL WONDERFUL AND
INTRIGUING AND INTERESTING.
I HAVEN'T HEARD ANYTHING ABOUT
ANY OF THIS.
HOWEVER -- I DON'T SWAN NOT
SERVING THE GREATER PURPOSE OF
THE RESEARCH.
THE SECOND THING I SAY IS THAT,
YOU KNOW, THIS IS NOT ABOUT YOUR
CHILD.
THIS IS ABOUT SCIENCE,
MEASUREMENTS, DATA COLLECTION.
THIS MAKES PEOPLE ANTSY.
IF PAUL ORCHARD TREATED EVERY
KID HE WOULD NOT HAVE MEANINGFUL
DATA TO SHOW THE FDA.
ALL THIS WORK WOULD BE FOR
NAUGHT.
I EXPLAINED THAT TO THE
COMMUNITY ON AS GENTLY AND
CALMLY AND RATIONALLY AS I CAN.
AGAIN, WITH THE TEFLON, KEVLAR
CHILD OF MY DAUGHTER COULD NEVER
BENEFIT.
I SAY DON'T BECOME A PATIENT
ADVOCATE IF YOU CAN'T ACCEPT THE
FACT YOUR KID WON'T BENEFIT.
IT'S A CONTROVERSIAL THING TO
SAY, SOME BEST WORK HAS BEEN
DONE BY PARENTS FOR THEIR
CHILDREN BUT IF YOU THINK THIS
IS THE ONLY OUTCOME THAT YOU
WANT, THEN DO SOMETHING ELSE
WITH YOUR TIME.
IT'S NOT GOOD FOR THE COMMUNITY
OR RESEARCH.
THAT'S MY EXPERIENCE, TEN YEARS
INTO THIS SPACE.
>> IT GOES BACK TO EARLIER
CONVERSATIONS, HAVE TO BEGIN
WITH PATIENT AND FAMILY
ORGANIZATIONS.
WHETHER INDUSTRY OR ACADEMIC,
HAS TO LISTEN TO WHAT'S
IMPORTANT TO THOSE FAMILIES.
THAT'S ESSENTIAL.
OUTCOME MEASURES ARE EQUALLY AS
IMPORTANT.
WE LOOK FOR BIOMARKERS BUT IN
ALL OF THAT, HAS TO BE CAREFULLY
LAID OUT ON BEHALF OF ADVOCACY
ORGANIZATIONS TO FAMILIES GENTLY
BUT DISCUSSIONS OF CRITERIA HAS
TO HAPPEN WITH INVESTIGATORS,
CLINICAL TEAM AND FAMILIES.
ONE STUDY, THE INDUSTRY HAD
STAFF MEMBERS TALKING TO
FAMILIES SAYING YOU'RE NOT
ELIGIBLE.
THAT IS NOT APPROPRIATE.
IT HAS TO COME FROM THE
CLINICIAN WHO KNOWS MEDICAL DATA
TO CAREFULLY AND GENTLY DISCUSS
THIS AND HAS TO BE ALSO
REALLY -- I LIKE THE WORD "CARE"
MORE THAN "CURE."
I WOULD SAY THEY ARE THE SAME
WORD, ONE LETTER DIFFERENT,
EQUALLY IMPORTANT.
WHEN I DISCUSS WHY A CHILD NOT
BE ELIGIBLE, I PIVOT AND DISCUSS
THINGS TO OPTIMIZE THAT CHILD'S
CARE, EQUALLY AS IMPORTANT FOR
THE NEXT STUDY COMING DOWN THE
PIPELINE, WE NEED THAT CHILD
OPTIMIZE THEIR CARE.
THAT'S A WHICH TO DEAL WITH A
DIFFICULT ISSUE, IT HAS TO BE A
DELICATE DISCUSSION BETWEEN
CLINICIAN AND FAMILIES.
>> DID YOU HAVE ANY COMMENTS ON
THIS?
>> THOSE ARE ALL REALLY
CRITICAL, REMINDING ME OF A FILM
CALLED "RARE" ABOUT -- I DON'T
KNOW IF PEOPLE HAVE SEEN IT IN
THIS ROOM BUT I RECOMMEND IT.
IT'S ABOUT A MOTHER AND A
DAUGHTER DUO, ABOUT THEIR
DIAGNOSTICS AND TREATMENT
JOURNEY WITH HERMANSKI PODLOX
SYNDROME, A SIMILAR STORY, CAME
TO THE NIH, NHGRI, HUMAN GENOME
RESEARCH INSTITUTE, THEY HAD
FOUND A SET OF INVESTIGATORS
THAT COULD TRANSLATE SOME BASIC
SCIENCE RESEARCH AND MOVE IT
INTO PHASE 1 AND 2 CLINICAL
TRIALS, AND HER OWN DAUGHTER WAS
INELIGIBLE FOR THE STUDY THAT
THEY EVENTUALLY GOT OFF THE
GROUND AND THERE'S LIKE THIS
REALLY HEART WRENCHING SCENE IN
WHICH HERE IS A MOM WHO HAS DONE
EVERYTHING, HAD THE BAKE SALES,
STARTED THESE FOUNDATIONS,
ACTUALLY GATHERED ALL OF THE 30
OF 30 PATIENTS IN THE UNITED
STATES THAT HAS THIS RARE
SYNDROME VIA SOCIAL MEDIA AND
OTHER RESOURCE CONNECTIONS AND
HER OWN DAUGHTER IS NOT ABLE TO
BE IN THE TRIAL BASED ON
INCLUSION AND EXCLUSION CRITERIA
SO I THINK THAT NOT TO ADDRESS
YOUR QUESTION WITH ACTIONABLE
ITEMS, RATHER THIS IS TO HAVE
RESEARCHERS REALLY UNDERSTAND
THE IMPACT THAT HAS ON FAMILIES
AND TO I THINK SEEING THAT KIND
OF ON FILM IT BRINGS THE EMOTION
THAT HAS TO HAPPEN WHEN YOU HAVE
THOSE CONVERSATIONS.
>> AND IS A TOPIC FREQUENTLY IN
MY JOB, RDCRN AND COALITION OF
PATIENT ADVOCATES THIS HAS COME
UP IN OUR DISCUSSION.
ARE THERE OTHER QUESTIONS IN THE
AUDIENCE?
OR ONLINE?
MY NEXT QUESTION FOR THE GROUP
THEN IS WHAT CHANGES DO YOU SEE
IN THE NEXT FIVE YEARS THAT ARE
GOING TO DRASTICALLY CHANGE THE
FIELD?
WHO WOULD LIKE TO START?
>> SURE.
SO, MAYBE UNSURPRISINGLY, I
SPENT A LOT OF THE LAST PROBABLY
TWO TO THREE YEARS ON THE
CLINICAL INTEGRATION OF
ARTIFICIAL INTELLIGENCE ACROSS
RESEARCH AND CLINICAL CARE.
AND ONE OF THE I THINK REALLY
EXCITING ADVANCES IN THIS AREA
IS WE MOVE AND FURTHER
SOPHISTICATE A.I. INTO CLINICAL
RESEARCH REALMS IS THE NEW IDEA
OF A DIGITAL TWIN.
AND DIGITAL TWINS ARE
ESSENTIALLY MULTI-MODAL REALLY
ADVANCED MULTI-MODAL DATASETS OF
EHR RECORD, EMERGING E HR WITH
WEARABLE WITH EXOME SEQUENCING,
CREATING A DIGITAL
REPRESENTATION OF THAT PERSON
WHICH CAN BE A STAND-IN FOR
FIRST-IN-HUMAN CLINICAL TRIALS
RESEARCH AS SOME SORT OF INITIAL
BEFORE PHASE 1 IMPOSED
PRE-CLINICAL AND IN ANIMAL
STUDIES.
WHAT'S REALLY EXCITING ABOUT
THIS, THERE'S STILL A LOT OF
WORK AND CONTROVERSY, IT REALLY
ADDRESSES SOME OF THE VERY ACUTE
ETHICAL CONCERNS WE HAVE IN
THOSE PHASE 1 TRIALS AND WE'RE
LEVERAGING MASSIVE DATASETS,
ABILITY TO SYSTEMATICALLY
ANALYZE AND ACROSS ANGLES AND
EXPOSURES.
THIS IS I THINK GOING TO BE
FURTHER ADVANCED IN THE NEXT
FIVE YEARS, TO WHAT POINT THEY
CAN BE AN ACTUAL STAND-IN TO
CLINICAL TRIALS IS AN
UNANSWERABLE QUESTION TODAY BUT
I AM REALLY ENCOURAGED BY JUST
THE AMAZING TECHNOLOGIES WE CAN
LEVERAGE IN MEDICAL A.I. AND
WORKED ALONGSIDE ADDRESSING SOME
OF THE ACUTE ETHICAL ISSUES.
SO CERTAINLY IN DATA PRIVACY AND
PROTECTION WE RECENTLY PUBLISHED
A PAPER A HOW A DIGITAL TWIN
COULD ACCOUNT FOR SOCIAL
DETERMINANTS OF HEALTH, SO WE
KNOW VERY LITTLE ABOUT
ENVIRONMENTAL HEALTH EXPOSURES,
WE KNOW THAT EDUCATION AND
INCOME AND OTHER SOCIAL FACTORS
HAVE VERY SIGNIFICANT IMPACT ON
PEOPLE'S HEALTH STATUS OVER THE
LIFE COURSE.
BUT MODELING THAT IN A POTENTIAL
A.I. TWIN AND USING THAT
REPRESENTATION IN VERY RISKY
TRIALS AT THE VERY EARLY STAGES
OF DRUG DEVELOPMENT WILL NEED A
LOT OF REFINING BUT THAT'S ONE
AREA WE'RE PAYING CLOSE
ATTENTION TO.
>> I WOULD EXTEND THIS WITH WHAT
YOU SAID ABOUT A.I., I WAS
ASKING A DISCUSSION WITH MARIA
BEFORE ABOUT SOMETIMES THERE'S A
REQUIREMENT FOR A PLACEBO
CONTROL GROUP AND MANY DISEASES
ARE DEVASTATING.
AND SO I THINK, MARIA, IF YOU
DON'T MIND EXTENDING THE
QUESTION ABOUT THE CONCERNS
ABOUT PLACEBO CONTROL IN THESE
TRIALS AND THEN IF ANYBODY WANTS
TO TALK ABOUT THE NEED FOR
PLACEBO.
>> THIS IS SO CRITICAL.
I FEEL LIKE -- I WANT TO HUG
EVERYBODY HERE BECAUSE WE
WOULDN'T BE THIS CLOSE HAD IT
NOT BEEN FOR THE NIH.
AND THEIR WORK IN NATURAL
HISTORY.
AND TINA ERB, WHEREVER YOU ARE,
RESPECT, LOVE.
TINA ERB, OUR PROGRAM OFFICER AT
THE RDCRN HAS SCHOOLED ME FOR
SEVERAL YEARS ON THE CRITICAL
ROLE OF NATURAL HISTORY DATA
COLLECTION.
AND DATA IS POLITICAL.
IT IS NOT OBJECTIVE.
IT IS POLITICAL.
AND THE FDA HAS A TREMENDOUS
CHALLENGE, WHICH IS THESE GENE
THERAPIES ARE COMING THROUGH,
VERY EXPENSIVE, NO ONE KNOW WHAT
IS THEY ARE.
THEY ARE PRETTY SCARY WHEN YOU
THINK ABOUT IT.
LENTIVIRAL VECTORS, WE DID A
PIECE AND I GOT CRAZY LETTERS.
I THOUGHT IT WAS AMAZING.
OTHERS THOUGHT IT WAS A
CONSPIRACY, BILL GATES COMING
FOR US OR SOMETHING.
IN ALL SERIOUSNESS, WE'RE IN A
SITUATION WHERE WE HAVE TO
ENGAGE WITH REGULATORS AS SOON
AS WE'RE THINKING OF A CLINICAL
TRIAL TO GET THEM COMFORTABLE
WITH THE DATA WE'RE GOING TO
HAVE.
AND THAT'S NOT -- AND I DON'T
BELIEVE IN WEAPONIZING HUMAN
EMOTIONS WITH THE FDA.
WE OWE A TREMENDOUS DEBT TO AIDS
ACTIVISM OF THE 1980s,
REVOLUTIONARY, BUT THROWING THE
ASHES OF YOUR LOVED ONE ON THE
WHITE HOUSE LAWN PROBABLY WON'T
GET YOU ANY WHERE THESE DAYS.
YOU NEED TO ENGAGE WITH FDA, USE
TOOLS OF NIH TO BE COMFORTABLE
SIGNING OFF A MULTI-MILLION
DOLLAR THERAPY THAT DOESN'T
NECESSARILY HAVE A HUGE DATASET.
OUR CLINICIANS INCLUDING THE
AMAZING PAUL ORCHARD WENT TO THE
FDA AND MADE IT CLEAR SOME
THINGS THEY WERE ASKING WERE
IMPOSSIBLE, IN PARTICULAR
PLACEBO CONTROL WITH A BONE
MARROW TRANSPLANT, FOR MLD
CHILDREN FACING 30% MORTALITY
RATE AND WE COULD NOT SIGN UP ON
A PLACEBO CONTROL ARM THAT WOULD
KILL 30% OF THE BABIES.
THAT DISCUSSION WAS
UNCOMFORTABLE FOR THE ACADEMIC
TEAMS.
WE DON'T KNOW WHAT WE DON'T
KNOW.
THEY LIKE TO HEDGE THEIR BETS.
WE HAD TO MAKE OUR CLINICAL
TEAMS LISTEN, SAY I DON'T WANT
TO USE THIS PLACEBO CONTROL ARM.
I KNOW YOU NEED IT TO COVER YOUR
FLANK, PART OF YOUR ANATOMY, YOU
DON'T WANT TO BE TAKEN OUT BY
THE "NEW YORK TIMES," RIGHT?
I GET THAT.
AT THE SAME TIME WE CAN'T SIGN
OFF.
YOU HAVE TO HAVE REALLY POINTED
CONVERSATIONS.
THE NIH IS SWITZERLAND, GIVING
THEM TO IS A DISCUSSION NOT
DRIVEN PURELY BY DESPERATE
PARENTS OR BUSINESS INTERESTS
LOOKING AT RUNWAYS RUNNING OUT
OF MONEY, WE'RE GOING TO GIVE
YOU EVERYTHING BUT WILL MOSTLY
NOT BE A PLACEBO CONTROL ARM.
>> I'LL ADD AT THE NIH
INTRAMURAL WE CAN DO PHASE 1
MORE RISKY FOR ACADEMIC MEDICAL
CENTERS.
IT'S A VERY GOOD LEARNING
PROCESS.
WE CAN DO ADAPTIVE TRIAL DESIGN,
SMALL NUMBER OF PATIENTS, RARE
DISEASES, FROM THAT DATA
MAXIMIZE INFORMATION TO GO
FORWARD TO PHASE 1/2 TRIALS,
IT'S KEY ALLIANCE BETWEEN THE
PATIENT AND FAMILY ORGANIZATIONS
AND RESEARCHERS TO REALLY
OPTIMIZE FROM THE PERSPECTIVE OF
RARE DISEASE SO WE'RE NOT
DEALING WITH ADULT POPULATION OR
LARGE POPULATION.
I'M BEEN ON ADVISORY COMMITTEE
MEETINGS WHERE COLLEAGUES ARE
EXPERTS IN ALZHEIMER'S, VERY
IMPORTANT BUT A VERY DIFFERENT
PERSPECTIVE THAN FOR EXAMPLE
DUCHENNE MUSCULAR DYSTROPHY,
UNIFORMLY FATAL, TO TUNE IN THE
RADIO DIAL TO THAT PATIENT AND
FAMILY, UNDERSTAND WHAT THAT
LIFESPAN IS, WHAT LIFE IS LIKE,
IS ABSOLUTELY KEY.
THE OTHER PART OF THAT TOO WHEN
YOU ARE -- HOW DO I PUT THIS?
WHEN YOU ARE TALKING ABOUT A
DISEASE LIKE MLD, OR A DISEASE
THAT IS JUST SO -- WELL, NIH IS
A CRITICAL TOOL.
I WAS JOKING THAT YOU'RE
TERRIBLE AT SELF-PROMOTION.
THE FIRST GENE THERAPY IN THE
WORLD HAPPENED HERE WITH ADA
SCID, AND FRENCH ANDERSON AND
ACHANTE D'SILVA, I HAVE A
PHOTOGRAPH OF THE 40-YEAR-OLD,
THE FIRST CHILD EVER TREATED
WITH GENE THERAPY HERE AT THE
NIH BECAUSE DR. ANDERSON AND HIS
TEAM BELIEVED THEY HAD A
SCIENTIFIC CONCEPT THAT COULD
WORK.
THEY WENT THROUGH 20 HOURS OF
PUBLIC HEARINGS TO GET APPROVAL,
WENT THROUGH THE FDA.
THE NIH DID ALL THIS WORK AND
ASHANTE WAS NOT A CANDIDATE FOR
BONE MARROW TRANSPLANT, THE
FAMILY HAD THE TOLERABLE RISK
THRESHOLD, AND THE NIH MADE THAT
POSSIBLE.
I THINK THE NIH IF WE GO BACK
HAS BEEN DOING THIS REALLY WELL
FOR ALMOST 40 YEARS.
WE NEED TO GIVE THE NIH
RESOURCES TOOLS, CONGRESS,
PRESIDENTS, FUND.
WE CAN'T ASK INDUSTRY AND CAN'T
ASK FAMILIES TO DO THIS, AS MUCH
AS AMAZING FAMILIES DO GREAT
WORK.
THERE ARE LIMITS TO WHAT WE CAN
DO.
>> WE HAVE A QUESTION.
THIS WILL BE OUR LAST QUESTION.
>> SHARON ROSSI, BRIGHT FOCUS.
I WASN'T SURE IF THIS WAS A
QUESTION FOR BEFORE OR NOW.
JUST INTERESTED IN YOUR THOUGHTS
ESPECIALLY BECAUSE ALZHEIMER'S
DISEASE SPACE, ON THE FDA MAYBE
ROLLING BACK NEED TO USE ANIMALS
FOR CLINICAL TRIALS, HOW THAT
MIGHT BE DIFFERENT FROM WHAT I
HEAR IN THE ALZHEIMER'S SPACE TO
RARE DISEASES THAT WE'RE TALKING
ABOUT TODAY.
>> FROM MY UNDERSTANDING, IT'S
VERY DISEASE-AREA SPECIFIC.
AND WHAT OTHER MODELS WOULD BE
AVAILABLE TO COMPENSATE.
SO YOU CAN USE ANIMAL MODELS TO
TEST FOR EFFICACY, DOES YOUR
THERAPY WORK, IN THE ANIMAL
MODEL, DOES IT ALLEVIATE
SYMPTOMS BUT ALSO ANIMAL MODELS
COULD BE USED FOR TESTING, JUST
REGULAR ANIMALS.
SO THERE ARE DISCUSSIONS ABOUT
WHETHER OR NOT NON-HUMAN
PRIMATES FOR EXAMPLE MAY BE
NECESSARY FOR TOX STUDIES AND
CERTAIN TYPES OF GENE THERAPY
BUT I THINK IT'S VERY
DISEASE-AREA SPECIFIC.
AND WHAT -- YOU KNOW, INDUCE THE
PLURIPOTENT STEM CELLS ARE
AVAILABLE OR ORGANOID MODELS, I
THINK IT'S REALLY HARD TO SAY,
AS IT'S A SPECIFIC DISEASE AREA
>> I THINK FROM WHAT WE DEAL
WITH, PEDIATRIC DISEASES, IT'S
ESSENTIAL WE HAVE THE JUVENILE
TOXICOLOGY DATA SO FOR US IT'S
NECESSARY, AND NON-HUMAN PRIMATE
DATA AS WELL.
BUT IT'S A GREAT QUESTION.
WE SAID WE WOULD BE PROVOCATIVE,
DIDN'T WE?
>> I WANT TO THANK EACH OF THE
SPEAKERS TODAY.
I THINK THEY DID GREAT JOB WITH
TOUGH QUESTIONS RELATED TO THE
ETHICS AND CHALLENGES AND GENE
THERAPY.
[APPLAUSE]
I'M HANDING OFF TO OUR --
REBECCA IS LOOKING AT ME.
THE NEXT MODERATOR CAN JOIN.
>> AND PANELISTS AS WELL.
>> THANKS SO MUCH.
>>I'M PENNY DAKS, FRONTOTEMPORAL
ORGANIZATION, WE'RE GOING TO
TALK ABOUT DIFFERENT STRATEGIES
THAT NON-PROFITS TAKE TO FUND
RESEARCH.
SO DIFFERENT THAN THE MORNING'S
DISCUSSION BUT A CENTRAL PART TO
WHAT NON-PROFITS SEEK TO DO.
AS NON-PROFITS WE HAVE TO
REMEMBER WE'RE A SMALL PIECE OF
A LARGE ECOSYSTEM FOR ADVANCING
TREATMENTS IN DIAGNOSTICS FOR
OUR CONDITIONS.
AND THE INTENTION OF TODAY'S
SESSION IS TO REVIEW BOTH
RESOURCES AND DIFFERENT
STRATEGIES THAT NON-PROFITS TAKE
TO FIND WAYS TO MOVE THE NEEDLE.
I SAW ANOTHER PERSON PRESENT ON
THE SIZE OF NON-PROFIT FUNDING
COMPARED TO NINDS.
IT IS QUITE BREATHTAKING BUT
MAKES IT SO PIVOTAL WE THINK
CAREFULLY HOW WE DESIGN OUR
FUNDING PORTFOLIOS TO FIND THE
GAPS THAT ARE NON-EASILY DONE BY
THE NIH AND LEVERAGE THE
RESOURCES OF LARGER FUNDERS LIKE
THE NIH.
SO I'M THRILLED WE HAVE A GREAT
SET OF PANELISTS HERE.
WE'LL START WITH CHRIS TORBORG
TO DESCRIBE HOW NIH RESOURCES
LIKE THE FEDERAL REPORTER CAN
HELP UNDERSTAND THE FUNDING
LANDSCAPE FOR ANY GIVEN
CONDITION.
AND THEN WE'LL HEAR ABOUT NOT
THE WHOLE PORTFOLIO, IT'S REALLY
SPECIFIC TO ONE OR TWO
STRATEGIES THAT THEY ARE TAKING
THAT IS A DIFFERENT APPROACH TO
TRY TO FUND RESEARCH.
WITH THAT I'LL TEE UP THE NEXT
SPEAKER.
SO DR. TORBORG.
>> SO THANKS.
I'M CHRISTINE TORBORG, OFFICE OF
SCIENCE POLICY AND PLANNING.
WE DO A WIDE VARIETY OF POLICY
ISSUES ACROSS FOR NINDS.
ONE OF THE BIG ISSUES WE WORK ON
ARE ANALYSIS OF PORTFOLIOS TO
UNDERSTAND IT.
I'M GOING TO GIVE A BROAD REVIEW
OF WHAT SOME TOOLS ARE, AND
THERE'S A LOT.
FIVE MINUTES IS HARD TO COVER IT
ALL.
THE ONE STOP SHOP THAT EVERYBODY
SHOULD KNOW OF IS NIH REPORT,
REPORT.NIH.GOV.
I TOOK A SCREEN SHOT OF THE HOME
PAGE.
YOU GO ACROSS THE TOP, START
CONTROLLING SCROLLING.
THERE'S LINKS TO EVERYTHING.
YOU CAN FIND VARIOUS TYPES OF
STRATEGIC PLANS ACROSS ALL OF
NIH, DIFFERENT STRATEGIC PLANS
CAN BE LINKED UNDER THE REPORTS
TOOL.
THERE'S WORKFORCE.
THERE'S ALL SORTS OF REPORTS
FROM NIH OFFICE OF DIRECTOR ON
THE BIOMEDICAL RESEARCH
WORKFORCE, WHAT'S NEEDED.
THERE'S A HUGE PLETHORA OF TOOLS
THERE TO LOOK.
I THINK FOR THE PURPOSES OF
UNDERSTANDING PORTFOLIO THERE'S
A FEW TOOLS MOST USEFUL FOR YOU.
ONE IS THAT WE HAVE THE NIH DATA
BOOK.
PRE-PREPARED REPORTS OF THE
NIH -- FREQUENTLY ASKED
QUESTIONS FOR NIH DATA.
THESE ARE ACROSS NIH, SORT OF
LIKE HOW MANY TRAINING GRANTS IS
NIH FUNDING, ET CETERA.
YOU CAN LOOK FOR THOSE REPORTS.
CATEGORICAL SPENDING IS REALLY
ABOUT THOSE CATEGORIES OR
SCIENTIFIC AND DISEASE
CATEGORIES WE'RE REQUIRED TO
REPORT TO CONGRESS, PUBLICLY
AVAILABLE DATA.
TODAY I WANT TO TALK MORE ABOUT
THE NIH REPORTER DATABASE, AN
INCREDIBLY POWERFUL TOOL FOR
IDENTIFYING GRANTS OF RELEVANCE.
HOPEFULLY IT'S EASY TO FIND.
IT ALLOWS YOU TO SEARCH ON A
WIDE VARIETY OF SEARCH FIELDS
SUCH AS P.I., RESEARCH
INSTITUTIONS, KEY WORDS, TEXT
BASE SEARCHES, ALL SORTS OF
THINGS.
IT HAS DATA BACK TO 1985.
YOU CAN LOOK AT CHANGES OVER
TIME.
THERE'S A HUGE NUMBER OF
ANALYSES.
SOME TOOLS IMPLEMENTED MORE
RECENTLY THAT ARE INTERESTING IS
THE MATCHMAKER FUNCTION.
IF YOU GO OVER HERE TO THE
MATCHMAKER AND GET STARTED, THAT
TOOL ALLOWS YOU TO CUT AND PASTE
ABSTRACT, IT WILL THEN FIND NIH
GRANTS THAT HAVE SIMILAR TOPICS
TO THAT ABSTRACT.
YOU CAN GET A LIST OF GRANTS.
FOR EXAMPLE, IF YOU'RE
PERHAPS -- IF YOU HAVE A
RESEARCH PROGRAM, SUPPOSED TO
GIVE OUT GRANTS, YOU MAY WANT TO
PUT IN THE ABSTRACT THIS TOOL TO
SEE WHAT ELSE NIH IS THERE BUT
TO IDENTIFY POTENTIAL
INVESTIGATORS WHO ARE DOING
SIMILAR RESEARCH WHO MIGHT BE
GOOD TO REVIEW THAT GRANT IF YOU
WANT TO.
WE USE THAT AT NIH.
THERE'S ALSO A PUBLICATION
SEARCH TO PUT IN THE PUBLIC MED
I.D., A PMID, ON PubMed, FOR
PUBLICATION, AND IT WILL SPIT
BACK, GIVE YOU BACK A LIST OF
THE GRANTS ASSOCIATED WITH THAT
PUBLICATION.
WHICH COULD ALSO BE HELPFUL.
THIS DATABASE INCLUDES DATA NOT
JUST FROM NIH BUT SOME DATA FROM
FDA, CDC, VA, AGENCY FOR
CHILDREN AND FAMILIES, AHRQ, AND
HRSA, I'M BLANKING ON WHAT IT
STANDS FOR.
IT'S ANOTHER FEDERAL AGENCY THAT
FUNDS RESEARCH.
THE DATA IS OFTEN NOT AS
COMPLETE AS NIH.
IF A GRANT IS NOT THERE IT
DOESN'T MEAN -- IF IT IS THERE
YOU CAN GET MORE INFORMATION.
NIH REPORTER IS CONSTANTLY
UPDATED, GRANTS APPEAR WITHIN
REPORTER WITHIN 7 TO 10 DAYS OF
BUDGET START DATE.
IT'S UPDATED WEEKLY.
USUALLY MONDAYS, THE BIG UPLOAD
AT NIH.
IF YOU DO DO A SEARCH, WHAT DO
YOU GET OUT?
WHAT I DID HERE, A SEARCH ON
ACTIVE GRANTS THAT HAVE
PARKINSON'S DISEASE IN THE
TITLE.
AND THE RESULT IS I GOT 182
PROJECTS.
YOU GET A LIST OF THE PROJECTS.
YOU CAN DO ADDITIONAL FILTERING
FOR THE FISCAL YEARS OR
ORGANIZATIONS, ET CETERA.
YOU CAN CREATE AUTOMATIC CHARTS
OF THE PROJECTS.
FOR EXAMPLE, YOU MIGHT WANT A
CHART TO SAY OF THE 182 GRANTS
WITH PARKINSON'S DISEASE IN THE
TITLE WHAT FRACTION WERE FUNDED
BY NINDS VERSUS NATIONAL
INSTITUTE ON AGING, THERE'S
AUTOMATIC CHARTS THAT CAN BE
MADE.
YOU CAN CREATE A MAP OF THE
UNITED STATES WITH WHERE ALL THE
GRANTS ACROSS THE COUNTRY.
THERE'S ALSO SOME TOOLS FOR
PUBLICATIONS, PATENTS,
PUBLICATIONS ASSOCIATED WITH THE
GRANTS.
YOU CAN CLICK ON INDIVIDUAL
GRANTS AND GET MORE INFORMATION
ABOUT INDIVIDUAL GRANTS.
YOU CAN EXPORT ALL OF THIS DATA
INTO FILES USING THE EXHORT
TOOL, HUGE NUMBERS OF DATA
FIELDS IF YOU WANT TO DO OTHER
FURTHER ANALYSES IN EXCEL.
WHEN YOU'RE LOOKING AT
INDIVIDUAL GRANTS THE TYPES OF
INFORMATION FOR THOSE GRANTS ARE
ALL ABOUT THE PROJECT
DESCRIPTIONS, THE FULL ABSTRACT,
PUBLIC HEALTH RELEVANCE
STATEMENT, PROJECT TERMS,
DETAILS ABOUT THE FUNDING, P.I.,
ORGANIZATION, WHO THE PROGRAM
OFFICIAL AT NIH IS.
FOR EXAMPLE IF YOU WANT TO KNOW
WHO IS LOOKING AT LET'S SAY
GENETICS AND PARKINSON'S
DISEASE, WHO DO I CONTACT?
LOOK AT GRANTS AND SEE WHO IS
THE MOST FREQUENTLY CITED
PROGRAM OFFICIAL, THE PERSON YOU
PROBABLY WANT TO CONTACT.
OR WHAT STUDY SECTIONS ARE THEY
BEING REVIEWED IN.
YOU CAN GET A LOT OF INFORMATION
ABOUT RESULTS OF THOSE STUDIES.
FOR EXAMPLE, IT HAS LINKS TO
PubMed WITH ALL OF THE
GRANTS THAT ARE THE PUBLICATIONS
THAT CITED THAT GRANT.
IF THERE'S A PATENT YOU CAN GET
A LINK TO PATENT OFFICE FOR THAT
GRANT, FOR THAT PATENT.
THERE ARE OTHER OUTCOMES.
I'VE NEVER SEEN THIS DATA FIELD
FILLED SO I DON'T KNOW WHAT GOES
IN THERE.
IT LINKS IF THERE ARE CLINICAL
TRIALS OR CLINICAL STUDIES
ASSOCIATED WITH THAT GRANT,
LINKS TO clinicaltrials.gov TO
GIVE MORE INFORMATION ABOUT THE
CLINICAL TRIALS.
IT CAN LINK TO PRESS RELEASES
WHEN THEY ARE OUT THERE.
CERTAINLY THE NIH PUT OUT A
PRESS RELEASE FROM STUDIES BASED
ON THAT GRANT.
YOU CAN GET HISTORY OF THE
GRANT, WHAT'S HAPPENED IN
PREVIOUS YEARS.
IT ALSO HAS A SIMILAR PROJECT
WHICH DOES THAT MATCHING TOOL.
THIS IS AN OVERVIEW OF THE DATA
THAT'S THERE.
YOU REALLY HAVE TO EXPLORE TO
SEE WHAT WORKS FOR YOU.
I DID WANT TO SAY A FEW
RESOURCES TO HELP YOU UNDERSTAND
IT BETTER, IT'S A LOT, SO THERE
ARE FREQUENTLY ASKED QUESTIONS
PAGES THROUGHOUT THE SITE YOU
MAY WANT TO INVESTIGATE AND
EXPLORE.
THERE'S ALSO, IF YOU GO TO
EXTRAMURAL NEXUS, THE LINK HERE,
IT'S ALL ABOUT NIH FUNDING.
IT GIVES YOU A LOT OF TIPS HOW
TO USE REPORTER IF YOU SEARCH,
THE HISTORY OF THE BLOGS, HOW TO
USE THAT.
THERE'S OTHER THINGS YOU MIGHT
WANT TO EXPLORE AS WELL.
FINALLY THE NIH REPORT SITE HAS
A CONTACT E-MAIL THAT YOU CAN
CONTACT IF YOU NEED ADDITIONAL
HELP.
THAT'S ALL I WANTED TO SAY, TO
MAKE SURE YOU KNOW IT'S THERE.
THERE'S A LOT THERE AND YOU
SHOULD EXPLORE IT IF YOU HAVE A
CHANCE.
>> I WANT TO ASK ONE COMMENT.
I OFTEN SEE PEOPLE PARTICULARLY
YOU'RE LIVING WITH A DISEASE, GO
TO NIH REPORTER, YOU DON'T SEE
YOUR DISEASE FUNDED AT THE LEVEL
OF OTHER DISEASES.
I WONDER IF YOU WANT TO REFLECT
FOR A MOMENT, IS THAT BECAUSE
IT'S THE NIH ON THIS NOT THAT,
THERE'S RESEARCHERS APPLYING FOR
GRANTS AND THOSE GRANTS ARE
REVIEWED FOR QUALITY AND
SOMETIMES THERE ARE WHOLE FIELDS
WITH TONS OF RESEARCHERS WORKING
IN THEM AND THE ROOT CAUSE IS
NOT NECESSARILY A TOP-DOWN
DECISION.
>> ABSOLUTELY WHAT WE THINK IS
USUALLY GOING ON IS THAT IT'S
REALLY THERE HASN'T BEEN A
GROUNDSWELL IN THE RESEARCH
FIELD OR ENOUGH ADVANCES TO
ATTRACT MORE PEOPLE.
SOMETIMES FINDING A GENE,
TALKING ABOUT GENE THERAPY, CAN
REALLY NOW SEED A RESEARCH AREA.
THE OTHER THING I WANT PEOPLE TO
THINK ABOUT IS TO NOT THINK
NARROWLY ABOUT HOW YOU DO YOUR
SEARCHES BUT TO THINK MORE
BROADLY.
SOMETIMES DEPENDING ON WHAT
THERMOMETERS YOU USE, WHAT DO
YOU CONSIDER RESEARCH.
THERE'S THINGS ON THE PERIPHERY
THAT ARE RELEVANT.
WE DO A LOT OF CODING AND
THINKING ABOUT -- WE HAVE TO DO
SOME REPORTING, HOW MUCH YOU
SPEND, IT'S NEVER A CLEAR LINE
WHERE YOU CUT IT OFF.
I HAVE PARKINSON'S DISEASE ON
THE MIND BECAUSE I DO A LOT WITH
THAT RIGHT NOW.
WE HAVE GRANTS TO STUDY, TO
IDENTIFY GENES, FOR EXAMPLE, IN
PARKINSON'S DISEASE BUT WE ALSO
HAVE GRANTS TO UNDERSTAND THE
BASAL GANGLIA CIRCUIT, PARTS OF
THE BRAIN INVOLVED, STUDYING IN
A NORMAL PERSON, IT'S STILL
RELEVANT TO PARKINSON'S BECAUSE
YOU HAVE TO UNDERSTAND HOW THE
BRAIN NORMALLY WORKS TO KNOW HOW
IT GOES WRONG.
DO YOU INCLUDE THAT PARKINSON'S
DISEASE RESEARCH OR BASIC
SCIENCE HOW THE BRAIN WORKS?
BOTH ARE REALLY IMPORTANT.
THAT'S THE OTHER PART I WANTED
TO SAY ABOUT THAT.
>> THANK YOU.
NEXT UP IS DEBRA NIEHOFF FROM
AFTD.
>> THANK YOU AND GOOD AFTERNOON.
I'M DEBRA NIEHOFF, THE DIRECTOR
OF RESEARCH AND GRANTS FOR THE
ASSOCIATION FOR FRONTOTEMPORAL
DEGENERATION, AFTD.
I'M GRATEFUL FOR THE OPPORTUNITY
TO TELL YOU A LITTLE BIT ABOUT
ONE OF OUR MOST EFFECTIVE
FUNDING STRATEGIES.
FOR OVER 15 YEARS AFTD HAS
LOOKED TO OTHER NON-PROFIT
FUNDING ORGANIZATIONS AS
PARTNERS.
BY WORKING TOGETHER
COLLABORATIVELY, WE'VE BEEN ABLE
TO ACCOMPLISH GOALS THAT WOULD
HAVE BEEN VERY CHALLENGING IF WE
HAD TRIED TO FUND THEM ON OUR
OWN.
WE'VE HEARD A LOT ALL DAY ABOUT
THE VALUE OF PARTNERSHIPS
BETWEEN RESEARCHERS AND PATIENT
ADVOCACY ORGANIZATIONS.
I'M GOING TO GIVE HERE A
FUNDER'S PERSPECTIVE ON VALUE
ADD FOR FUNDING PARTNERSHIPS
PARTNERSHIPS CAN ALLOW
YOU TO ADD ADDITIONAL RESOURCES
TO EXISTING PROGRAMS.
YOU MIGHT BE ABLE TO FUND
ADDITIONAL AWARD IN A FUNDING
CYCLE BECAUSE THAT PROJECT HAS
RELEVANCE TO BOTH ORGANIZATIONS.
SECONDLY, FUNDING PARTNERSHIPS
HAVE ALLOWS US TO INITIATE NEW
PROGRAMS AND TO LEVERAGE NOT
ONLY SHARED FINANCIAL RESOURCES
BUT ALSO RESOURCES SUCH AS
EXPERTISE AND CLINICAL OR
SCIENTIFIC NETWORKS.
I'M GOING TO TELL YOU ABOUT ONE
OF THE NEW PROGRAMS IN JUST A
FEW MINUTES.
FINALLY FUNDING PARTNERSHIPS
ALLOW US TO BREAK DOWN THE SILOS
THAT SEPARATE DISEASE SPACES AND
REPLACE THEM WITH BRIDGES.
WE'VE USED THESE PARTNERSHIPS TO
DO JUST THAT AND TO BUILD
BRIDGES BETWEEN FTD AND OTHER
NEURODEGENERATIVE DISEASES.
THIS IS A SNAPSHOT OF CURRENT
RESEARCH GRANT PORTFOLIO,
BASICALLY OUR GRANTS FALL INTO
FOUR CATEGORIES.
WE HAVE FELLOWSHIPS THAT SUPPORT
RESEARCHERS WHO ARE STILL
FINISHING THEIR TRAINING AND NOT
YET EMBARKING ON AN INDEPENDENT
RESEARCH PROGRAM.
WE FUND PILOT GRANTS FOR EARLY
CAREER RESEARCHERS.
WE FUND A NUMBER OF PROGRAMS
THAT SUPPORT BOTH PRE-CLINICAL
AND CLINICAL DRUG DEVELOPMENT.
FINALLY PROJECTS AND PROGRAMS
THAT FOCUS ON BIOMEDICAL
DISCOVERY AND DEVELOPMENT.
WITH THE EXCEPTION OF THE PILOT
GRANT ALL OF OUR OTHER PROGRAMS
ARE EITHER PARTNERSHIP PROGRAMS
OR THEY ARE PROGRAMS WHERE WE
HAVE FUNDED ONE OR MORE TARGETED
PROJECTS THAT, AGAIN, HAVE
RELEVANCE FOR BOTH
ORGANIZATIONS.
I'M GOING TO GIVE A FEW EXAMPLES
OF PARTNERSHIP PROGRAMS AND WHAT
THEY HAVE ALLOWED US TO DO.
FIRST OF ALL I WANT TO TALK
ABOUT OUR FELLOWSHIPS.
WE HAVE GIVEN POSTDOCTORAL
FELLOWSHIPS SINCE 2009 BUT THE
ORIGINAL FUNDING MECHANISM
REALLY DIDN'T GIVE US THE
OPPORTUNITY TO FOCUS ON SPECIFIC
NEEDS OF CLINICIAN RESEARCHERS
WHO FACE SPECIAL CHALLENGES IN
TERMS OF COST AND ALSO DEVOTING
TIME TO THEIR RESEARCH AND
BALANCING THAT WITH THEIR
CLINICAL RESPONSIBILITIES.
IN ADDITION WE WANTED TO ENGAGE
PEOPLE IN FTD RESEARCH EARLY IN
CLINICAL CAREERS AND BECOME NOT
ONLY RESEARCHERS BUT ALSO
AMBASSADORS, TO RAISE AWARENESS
OF FTD AS ONE OF THE LESS COMMON
DEMENTIAS, OFTEN MISDIAGNOSED OR
NOT RECOGNIZED EVEN BY
SPECIALISTS.
WE WERE ABLE TO PARTNER WITH THE
AMERICAN BRAIN FOUNDATION AND
THROUGH THEIR COLLABORATION WITH
THE AMERICAN ACADEMY OF
NEUROLOGY WE WERE ABLE TO FUND
ONE OF AAN'S CLINICAL RESEARCH
TRAINING SCHOLARSHIPS
SPECIFICALLY FOR FTD.
THE PHOTOS YOU SEE HERE ARE THE
TWO FIRST RECIPIENTS OF THE
SCHOLARSHIP AND WE ARE VERY
HAPPY TO LEARN THAT OUR FIRST
WINNER, INDIRA GARCIA CORDERO,
IS GOING TO FULFILL THAT SECOND
GOAL AND SHE IS PLANNING TO
RETURN SOON TO HER NATIVE
ARGENTINA WHERE SHE HOPES TO
RAISE AWARENESS OF FTD AND
DEMENTIA IN GENERAL IN LATIN
AMERICA.
WE ALSO HAVE A NEW PROGRAM,
EXAMPLE OF HOW PARTNERSHIPS CAN
LET YOU DEVELOP NEW INITIATIVES.
THIS IS A PARTNERSHIP WITH THE
ALS ASSOCIATION.
FTD AND ALS WERE FOR A LONG TIME
THOUGHT TO BE SEPARATE
DISORDERS.
WE KNOW THERE ARE MANY
COMMONALITIES BOTH AT THE
CLINICAL LEVEL AND ALSO AT THE
BIOLOGICAL LEVEL.
SO WE HAVE OVERLAPPING CLINICAL
PRESENTATIONS.
SOME INDIVIDUALS WITH ALS
DISPLAYING THE BEHAVIORAL AND
LANGUAGE SYMPTOMS OF FTD AND
VICE VERSE THAT, DISPLAYING
MOTOR SYMPTOMS OF MOTOR NEURON
DISEASE.
THERE ARE ALSO SIMILARITIES IN
TERMS OF BIOLOGY AT THE
MOLECULAR AND CELLULAR LEVEL,
AND, FOR EXAMPLE, THE MUTATION
OF THE C 9 ORF 72 GENE, THE MOST
COMMON GENE MUTATION IN FTD IS
ALSO THE MOST COMMON GENE
MUTATION IN ALS.
BUT DESPITE THE SIMILARITIES
THERE'S NOT A CLINICAL
ASSESSMENT MEASURE USED BROADLY
ACROSS THE ENTIRE FTD/ALS
SPECTRUM.
ALS AND FTD ALSO PRESENT
CHALLENGES IN TERMS OF CLINICAL
CARE AND RUNNING CLINICAL TRIALS
BECAUSE THEY ARE DEVASTATING
DISORDERS WHERE PEOPLE ARE
CHALLENGED TO GET BACK AND FORTH
TO THE CLINIC AND WHERE THEIR
BEHAVIOR IN PARTICULAR IN THE
CLINIC IS OFTEN NOT THE BEHAVIOR
YOU SEE AT HOME.
DIGITAL TOOLS OFFER WAYS TO GET
AROUND THOSE PROBLEMS BUT
DESPITE A PLETHORA OF DIGITAL
TOOLS MAKING IT THROUGH THE
PILOT STAGE VERY FEW HAVE
CONTINUED TO ADVANCE ALONG THE
PIPELINE TOWARDS VALIDATION.
THIS PROGRAM AIMS TO ADDRESS ALL
OF THOSE NEEDS.
AND SO IT WILL ADVANCE THE
FURTHER DEVELOPMENT OF DIGITAL
TOOLS AT THE INTERSECTION
BETWEEN ALS AND FTD, AND IT WILL
SPECIFICALLY ASK THAT THE TOOLS
BEING TESTED ALREADY HAVE
PRELIMINARY DATA AND ARE READY
TO ADVANCE BEYOND THE PILOT
STAGE.
FOR THE THIRD EXAMPLE I'D LIKE
TO TALK A LITTLE BIT ABOUT OUR
PROGRAMS THAT WE FUND IN
PARTNERSHIP WITH THE ALZHEIMER'S
DRUG DISCOVERY FOUNDATION.
WE HAVE THESE PROGRAMS LOOKING
AT PRE-CLINICAL AND CLINICAL
LEVEL.
ACCELERATING DRUG DISCOVERY FOR
FTZ OUR LONGEST RUNNING
PARTNERSHIP PROGRAM, DISCOVERED
DRUG DISCOVERY AND PRE-CLINICAL
RESEARCH THAT NOW FOCUSES
SUPPORTING FURTHER DEVELOPMENT
OF LEAD COMPOUNDS THROUGH
SUPPORT FOR LEAD OPTIMIZATION,
IN VIVO EFFICACY STUDIES IN
ANIMALS.
WE WERE ABLE TO BUILD ON THAT
PARTNERSHIP TO FUND EARLY STAGE
CLINICAL TRIALS SINCE 2016.
AND WE CURRENTLY HAVE FOUR SUCH
ACTIVE TRIALS AND THEY ARE
LOOKING AT BOTH NOVEL AGENTS AND
ALSO REPURPOSED DRUGS.
SINCE 2015, OUR PARTNERSHIP
PROGRAMS HAVE AWARDED OVER $20
MILLION ACROSS SIX BRANT
PROGRAMS AND THESE ARRANGEMENTS
ALLOWED US TO ACHIEVE FUNDING
GOALS SUCH AS SUPPORTING
CLINICIAN RESEARCHERS, TO
LEVERAGE RESOURCES, AGAIN NOT
JUST TIME BUT ALSO EXPERTISE,
AND RESEARCH NETWORKS TO ALIGN
RESEARCH INTERESTS ACROSS
DISEASE SPACES, AND IMPORTANTLY
TO BUILD STRONG AND PRODUCTIVE
RELATIONSHIPS WITH OTHER
NON-PROFITS THAT WE HOPE WE WILL
BE ABLE TO BUILD ON TO OFFER
ADDITIONAL SUCH PROGRAMS IN THE
FUTURE.
BEFORE I SIT DOWN I WANT TO
THANK ALL OF YOU WHO TOLD YOUR
STORIES TODAY.
THEY WERE INCREDIBLY COMPELLING.
AND THEY ARE A REMINDER OF WHY
WE FUND RESEARCH AND AN
INSPIRATION FOR OUR RESEARCH
COMMUNITY.
THANK YOU.
>> NEXT UP MANNISH RAISINGHANI
DELIVERING HIS TALK VIRTUALLY.
>> AN INTRODUCTION, TARGET ALS
FOUNDATION, WE'RE IN EXISTENCE
SINCE 2013 TO FINDING EFFECTIVE
TREATMENT FOR ALS.
WE ARE A BIOMEDICAL RESEARCH
FOUNDATION, WHAT DIFFERENTIATED
US IS APPROACH WE'VE TAKEN TO
FUNDING ALS RESEARCH.
WE FEEL THERE ARE LESSONS THAT
MAY BE APPLICABLE TO OTHER
DISEASE AREAS AS WELL.
WHEN WE STARTED IN 2013 THE
FIRST TASK TO UNDERSTAND WHAT
WERE KEY BARRIERS STANDING IN
THE WAY OF ALS RESEARCH AND DRUG
DISCOVERY.
IT WAS DISCOVERED 150 YEARS AGO,
PROGRESS WAS SLOW AND ITERATIVE.
WHAT WE FOUND WHEN WE STARTED
WAS THAT THERE WERE SIX KEY
BARRIERS STANDING IN THE WAY OF
PROGRESS.
THEY ARE LISTED ON THE SLIDE
HERE.
SOME OF THESE YOU'LL FIND TO BE
FAMILIAR, NOT NECESSARILY UNIQUE
TO ALS RESEARCH COMMUNITY.
BUT WHAT HAPPENS IS THESE ARE
BARRIERS THAT ARE FACED BY ALL
DIFFERENT EFFORTS ON DIFFERENT
DISEASE AREAS, BUT PARTICULARLY
ACUTE WHEN IT COMES TO SMALLER
RESEARCH COMMUNITIES.
SO WHAT WE FOUND THERE WAS A
REAL GAP IN FUNDING FOR
TRANSLATIONAL RESEARCH AND
INCENTIVES FOR PEOPLE TO WORK
TOGETHER COLLABORATIVELY.
WHAT WE ALSO FOUND WAS THAT THE
APPROACH TO RESEARCH, WITHIN
ACADEMIA, MORE SO WHEN IT CAMES
TO ACADEMICS, GROUPS WORKING
TOGETHER.
WE ALSO FOUND THERE WAS A REAL
BARRIER TO WORKING ON ALS
BECAUSE OF CHALLENGES IN
ACCESSION AN ANTIBODY TO ANIMAL
MODELS TO PRECIOUS HUMAN B
IOSPECIMENS.
THERE WAS LIMITED INVESTMENT IN
ALS RESEARCH.
ANOTHER KEY ISSUE WAS AS YOU
KNOW WE TYPICALLY RELY ON PEER
REVIEW PROCESS TO MAKE FUNDING
DECISIONS.
THEY WORK WELL BUT HAVE
CHALLENGES, EXACERBATED WITH
SMALLER RESEARCH COMMUNITIES
BECAUSE OF THE SAME PEOPLE GOING
TO ACCESS FUNDING ARE MAKING
DECISIONS, THERE'S A POTENTIAL
FOR RESOURCES (INDISCERNIBLE).
SEVERAL ISSUES WITH LICENSING
AGREEMENTS, DISCOURAGING
PARTICIPATION FROM TECH AND
RESEARCH COMMUNITIES.
THE APPROACH WAS TO CREATE
ECOSYSTEMS WITH SIX STRATEGIES
SHOWN HERE MUTUALLY REINFORCING,
MEANT TO ADDRESS BARRIERS THAT
WE IDENTIFIED.
THE FIRST WAS EXCLUSIVELY FUND
COLLABORATIVE PROJECTS,
SCIENTISTS HAVE TO COME
TOGETHER, WORK ON THE SAME IDEA
TOGETHER.
MOVE THE IDEA FORWARD OR COME TO
A GO/NO-GO DECISIONS.
WE IN SOME FUNDING OPPORTUNITIES
REQUIRED OPEN-ENDED
COLLABORATION, ONLY ACADEMICS,
BUT IN SOME FUNDING REQUIRED
BIOTECH BE A COLLABORATOR.
WE WANTED TO DEMOCRATIZE ALS
RESEARCH AND LOWER BARRIERS,
CREATING CORE FACILITIES THAT
CREATE, COLLECT, PROVIDE ACCESS
TO SCIENTIFIC TOOLS AND
RESOURCES, ANTIBODIES TO HUMAN
STEM CELLS, GENOMIC DATASETS TO
BIOFLUID SAMPLES, ALLOWED ANYONE
IN THE WORLD TO WORK ON THIS
WITHOUT ENTER IN COLLABORATION,
ONLY TO ACCESS THESE TOOLS.
THE THIRD THING, WHEN WE
LAUNCHED, WE LAUNCHED
INITIATIVE, TOOK THEM ALONG, WE
ALSO HAVE REPRESENTATION OF
PHARMA BIOTECH ON BOARDS, REVIEW
COMMITTEE, HIRED FROM THE
INDUSTRY AND ADVISORS AS WELL.
TO ENSURE WE HAVE A CONFLICT OF
INTEREST FREE AND PROCESS FOR
REVIEW OF FUNDING DECISIONS,
USING PEER REVIEW HAVE AN
INDEPENDENT REVIEW COMMITTEE.
BY DESIGN THIS COMMITTEE IS 50%
FROM ACADEMIA, NON-PROFIT, 50%
FROM CAPITAL.
REFLECTING THE NEED OF ALS
RESEARCH.
VERY FEW FROM THE COMMUNITY
ITSELF BECAUSE WE WANT EVERYONE
TO APPLY.
MEMBERS CAN APPLY FOR OR RECEIVE
TARGETING ALS FUNDING, THIS HAS
GIVEN A POSITION OF CREDIBILITY.
ANYONE CAN APPLY AND GET FUNDING
IRRESPECTIVE WITH BOARD MEMBERS
OR ANYONE ELSE.
A KEY PRINCIPAL HAS BEEN FUNDING
ALLOWS INVESTIGATORS IN ACADEMIA
OR PHARMA BIOTECH TO RETAIN
RIGHTS TO THEIR DATA AND
INTELLECTUAL PROPERTY.
WE WANT NOTHING IN RETURN.
THIS IS IMPORTANT GETTING
VENTURE CAPITAL AND BIOTECH
INVOLVED, GETTING LAUNCHED.
LASTLY A HUB OF NETWORKING AND
COMMUNICATION FOR RESEARCH
COMMUNITY WORLDWIDE.
WE SPEAK TO ACADEMICS,
NON-PROFITS, VENTURE CAPITAL,
CONNECT THEM BASED ON
OVERLAPPING INTEREST AND MOVE
OUT OF THE WAY.
THE IDEA IS TO FACILITATE, NOT
GAIN CREDIT.
THESE HAVE ALLOWED US TO IMPACT
RESEARCH IN A SIGNIFICANT WAY.
I'M GOING TO ILLUSTRATE A POINT
ABOUT THESE PROJECTS WE FUND.
TYPICALLY IT MEANS INVESTIGATORS
COME TOGETHER WORKING ON THEIR
OWN IDEAS, FUNDING FROM A COMMON
POOL, THEY WORK IN THEIR OWN
LABS.
IN OUR CASE WE REQUIRE BY
DEFINITION SCIENTISTS HAVE TO
SHOW COMPLEMENTARY EXPERTISE,
ALL THE PROJECTS WE FUND BY
DESIGN ARE MULTI-DISCIPLINARY,
SHOWN ON THE RIGHT.
OF 59 PROJECTS, FOUR TO SIX
COLLABORATORS, 60% HAD A PHARMA
BIOTECH BASED SCIENTIST LIED THE
PROJECT, HAVE REPRESENTED
SCIENTISTS FROM 32 COMPANIES, 60
ACADEMIC INSTITUTIONS WORLDWIDE.
WE HAVE CREATED ACCESS TO
RESEARCH TOOLS AND RESOURCES.
BY PROVIDING TOOLS WE KNOW THEY
HAVE BEEN USED BY OVER 975
PROJECTS WORLDWIDE NOW.
THIS IS A QUANTITATIVE IMPACT
BUT THERE'S A COLLABORATIVE
IMPACT.
IF IT WASN'T FOR ACCESS TO TOOL
THEY MAY NOT HAVE GOTTEN DATA
USED FOR R01 GRANTS TO BE
SUCCESSFUL.
IN TERMS OF IMPACT WE'VE SEEN
USING THESE STRATEGIES, 60% OF
COLLABORATIVE PROJECTS HAVE LED
TOEN ON GOING DRUG.
WE CALL THIS A 7-PILLAR
STRATEGY.
WE KNOW AS SCIENCE EVOLVES WE'RE
KEEN ON DIVERSIFYING, LOOKING AT
WHICH DISCIPLINES TO ENGAGE IN,
PARTNER WITH ORGANIZATIONS
WORKING ON RELATED
NEURODEGENERATIVE DISEASES TO
BRING IN EXPERTISE AS WELL.
WE'LL MAINTAIN AND EXPAND TO
PROVIDE CRITICAL RESEARCH TOOLS.
WE PARTNER WITH OTHER DISEASE
ORGANIZATIONS TO BRING IN TALENT
AND EXPERTISE.
THE CORE OF THE STRATEGY TO
DISCOVER AND DEVELOP NEW
TREATMENTS, TOOLKIT OF
BIOMARKERS BECAUSE ALS DOES NOT
HAVE ONE.
WE WANT TO TREAT ALL FORMS, BUT
PARTNERING WITH OTHER
ORGANIZATIONS AND GROW OUR
ORGANIZATION AS WE MOVE FORWARD.
I'LL STOP AND THANK YOU FOR YOUR
ATTENTION AND LATER BE HAPPY TO
ANSWER ANY QUESTIONS YOU HAVE.
WE'RE GOING TO OUR NEXT SPEAKER
AND HAVE A GROUP PANEL
DISCUSSION.
VICKY CATTANI, PARKINSON'S
FOUNDATION, IS NEXT UP.
>> THANK YOU FOR INVITING THE
FOUNDATION AND ME.
I WANT TO ECHO THE COMMENTS,
THANK YOU TO EVERYONE WHO SHARED
YOUR STORIES.
I'M ASSOCIATE DIRECTOR OF
RESEARCH PROGRAMS AT THE
PARKINSON'S FOUNDATION.
OUR MISSION IS TO MAKE LIFE
BETTER FOR PEOPLE WITH
PARKINSON'S BY IMPROVING CARE
AND ADVANCING RESEARCH TOWARD A
CARE.
OUR FOUNDATION FOCUS IS VERY
SPECIFIC.
THAT'S WHY THE NAME IS
PARKINSON'S FOUNDATION.
AND THAT IS, YOU KNOW, CONTRARY
TO KIND OF WHAT NINDS DOES,
DIVERSE PORTFOLIO OF
NEUROSCIENCE.
WE HAVE A FORECAST USED AND
RESEARCH AREA.
WE INCENTIVIZE SCIENTISTS TO
DEVOTE CAREERS TO PARKINSON'S
DISEASE RESEARCH.
WE WANT THEM TO KICK START THE
INNOVATIVE IDEAS OF NEW
SCIENTISTS AND GRANTS,
FELLOWSHIPS, PARTNERSHIPS.
PROVIDE SCIENTISTS WITH FUNDING
SO THEIR PROMISING IDEAS ARE
EXPLORED.
WE DO THAT TO FELLOWSHIP,
GRANTS, AWARDS.
I WANT TO FOCUS ON THESE TYPES
OF AWARDS.
WE HAVE OTHERS WE CAN DISCUSS
ONE ON ONE LATER.
AND I WANT TO REALLY FOCUS ON
THESE BECAUSE IN PARTICULAR THE
EARLY CAREER INVESTIGATORS, AND
LAUNCH AWARDS ON THE BOTTOM IN
YELLOW ARE REALLY -- THEY REALLY
COMPLEMENT EACH OTHER FOR
INVESTIGATORS TO CONVINCE THEM
TO REALLY STAY IN PARKINSON'S.
BECAUSE THEN THEY GET THIS
FUNDING AND THEN THEY GET VERY
KEY DATA THAT THEY CAN THEN
LEVERAGE TO GET THE FIRST R01.
AND WE SAY CRITICAL BECAUSE A
LOT OF THESE SCIENTISTS MAY
START IN PARKINSON'S BUT THEN
THEY SAY, WELL, YOU KNOW, I
APPLY FOR R01S BUT DON'T GET
THEM, I'M GOING TO SWITCH FOR
ALZHEIMER'S WHICH MIGHT GET
FUNDED.
WE WANT THEM TO STAY IN
PARKINSON'S BECAUSE IT'S A VERY
COMPLEX DISEASE.
AND WE DON'T HAVE A CURE.
WE CAN DOUBLE THE AMOUNT OF
POSTDOCS DOING PARKINSON'S
DISEASE RESEARCH.
IF YOU LEARN HOW TO USE NIH
REPORTER AND LOOK FOR NUMBER OF
POSTDOCTORAL FELLOWSHIPS, LOOK
AT THE NUMBER OF AWARDS THAT
HAVE BEEN GIVEN TO POSTDOCS OR
PRE-DOCS STUDYING PARKINSON'S IN
THE LAB A FEW YEARS YOU CAN SEE
NUMBERS ARE NOT THAT HIGH, NOT
THAT MANY YOUNG SCIENTISTS DOING
POSTDOCTORAL RESEARCH ON
PARKINSON'S DISEASE.
WE DON'T GIVE THAT MANY
FELLOWSHIPS, BUT EVEN IF WE GIVE
FIVE OR SIX EVERY YEAR WE'RE
DOUBLING THE NUMBER OF FELLOWS
STUDYING PARKINSON'S DISEASE.
WHICH WE THINK IS GREAT.
SO, OUR FOCUS IS TO REALLY
ENCOURAGE THESE YOUNG SCIENTISTS
TO STAY IN PARKINSON'S DISEASE,
BE SUCCESSFUL AT IT.
TO BE REALLY THE AMBASSADOR FOR
OUR FOUNDATION.
IF YOU LOOK AT OUR POSTDOCTORAL
FELLOWS, WE'VE BEEN GIVING SINCE
2002, EVEN BEFORE THE FOUNDATION
WAS ACTUALLY A PARKINSON'S
FOUNDATION, OF 92 POSTDOCTORAL
FELLOWS FUNDED, MOST OF THEM ARE
STILL ACTIVE DOING PARKINSON'S
DISEASE RESEARCH WHICH I THINK
PERSONALLY IS A LOT.
75% OF THEM REMAIN ACTIVE IN
ACADEMIA.
WHICH WE KNOW THE CRISIS TODAY
IS AMAZING.
IF WE LOOK AT THE JUNIOR
P.I.s, WE'VE BEEN GIVING THIS
AWARD SINCE 2016, FUNDED 12, 85%
STILL DOING RESEARCH IN
PARKINSON'S DISEASE, IN CONTRAST
TO OTHER NEURODEGENERATIVE
DISEASES.
MORE THAN HALF HAVE ALREADY
ADVANCED TO ASSOCIATE PROFESSOR,
PROBABLY THEY HAVE GOTTEN AN
R01.
INVESTMENTS PAY OFF.
IF WE LOOK AT RETURN ON
INVESTMENT, FOR EVERY DOLLAR WE
HAVE SPENT IN YOUNG SCIENTISTS,
RETURN OF INVESTMENTS, IN 2016
WE BECAME THE NEW FOUNDATION,
RETURN ON INVESTMENT FOR EVERY
DOLLAR HAS BEEN 4.4.
OUR INVESTMENT IN SCIENCE IS
DRIVING FORWARD WITH MORE AND
MORE PARKINSON'S DISEASE
RESEARCH.
IMPORTANTLY WE GO BEYOND THE
GRANTS, WHY WE THINK IT'S SO
IMPORTANT TO INVEST IN THE
PEOPLE THAT WE FUND.
THEY FEEL LIKE THEY, YOU KNOW,
WE DO REALLY CARE AND WANT THEM
TO BE SUCCESSFUL.
WE ORGANIZE ANNUAL SUMMIT TO
TALK ABOUT THE WORK WHERE THEY
NETWORK, WHERE THEY NEED OUR
ADVISORY BOARD MEMBERS THAT THEY
BECOME MENTORS FOR THEM.
THIS IS THESE ARE PICTURES OF
THEM DURING COVID.
IT WAS TOWARDS THE END OF THE
SECOND YEAR, SHOWING SCIENTIFIC
WORK TO SOME OF ADVISORY BOARD
MEMBERS AND PEOPLE FROM THE
FOUNDATIONS.
THIS IS A COHORT.
WE SUBSIDIZE ATTENDANCE TO
SCIENTIFIC CONFERENCES.
THESE ARE SOCIETY FOR
NEUROSCIENCE MEETING LAST YEAR,
SOME DOING POSTERS, POSTDOCTORAL
FELLOWSHIP AWARDEES, SUMMER
AWARDEES, GRATEFUL BECAUSE WE
PAID ATTENDANCE TO CONFERENCE.
WE ALSO AMPLIFIED SUCCESS IN
SOCIAL MEDIA.
IF THEY GET AN AWARD WE SAY
CONGRATULATIONS AND WHY.
IF WE WANT TO SAY THEY PUBLISHED
SOMETHING, WE WANT TO READ THEIR
PAPERS, WE DO IT.
IF THEY ARE A CONFERENCE, CITED
FOR NEUROSCIENCE, IF THEY WROTE
A REVIEW WE PUT THAT IN OUR
TWITTER.
AND WE ALSO PROVIDE PROFESSIONAL
DEVELOPMENT OPPORTUNITIES TO
THEM.
EITHER AT OUR SUMMIT OR THROUGH
WEBINARS OR STUFF.
WE ALLOW POSTDOCS TO BE
REVIEWERS IN OUR PANELS.
WE THINK IT'S A GREAT
OPPORTUNITY FOR THEM.
AND WE HAVE PROVIDED OTHER TYPES
OF WORKSHOPS THAT WE THINK WILL
ALLOW THEM TO BE SUCCESSFUL IN
THEIR SCIENTIFIC COMMUNITIES.
YOU CAN COME AND TALK TO ME
LATER OR IF YOU HAVE ANY
PARTICULAR QUESTIONS ABOUT OUR
GRANTS OR FELLOWSHIP FOUNDATION,
YOU CAN E-MAIL US.
>> PAUL GROSS WITH IT'S CEREBRAL
PALSY RESEARCH FOUNDATION IS
UNABLE TO JOIN US TODAY.
WE'RE MISSING OUT ON HEARING THE
RESEARCH STRATEGIES THAT THEY
USE BUT WE HAVE SOME TIME FOR
DISCUSSION.
WE'RE OPENING THE FLOOR, ANY
QUESTIONS, WE'RE HAPPY TO HEAR
FROM YOU WHAT YOU'D LIKE THE
PANEL TO DISCUSS.
I'M ALWAYS HAPPY TO TALK EVEN
IF -- I'LL KEEP ASKING QUESTIONS
UNLESS SOMEBODY STARTS ASKING
THEM.
I HAVE A VERY QUESTION FOR
CHRISTINE, DIVE INTO THE
CATEGORIES OF WHAT'S IN NIH
REPORTER.
I ASK THAT FROM PAST EXPERIENCE
WHERE EPILEPSY, FOR EXAMPLE,
WHICH TYPES ARE BEING FUNDED BUT
IN TERMS OF WHICH TYPES OF
RESEARCH WITHIN EPILEPSY ARE
BEING REFOUNDED.
IT'S INTERESTING TO BE ABLE TO
UNDERSTAND WHERE BASIC SCIENCE
FUNDING IS VERSUS MAYBE OUTCOMES
RESEARCH TYPES OF FUNDING VERSUS
SO MANY TYPES OF RESEARCH
FUNDING, EPIDEMIOLOGY.
CAN YOU TALK ABOUT THE OTHER
CATEGORIES OF WHAT'S IN NIH
REPORTER?
NIH REPORTER, IT'S ALL OF THE
WANTS WE FUND.
IT'S A TOOL THAT IS A DATABASE
FOR ALL THE GRANTS THAT ARE
FUNDED.
THERE ARE SORT OF PROJECT TERMS
THAT CAN BE AUTOMATICALLY
APPLIED THAT ARE AUTOMATICALLY
APPLIED THROUGH AN ALGORITHM TO
THE GRANTS SO YOU CAN SEARCH ON
MULTIPLE PROJECT TERMS IF YOU
WANT TO, SAY, IF YOU'RE LOOKING
AT FTD AND WANT TO UNDERSTAND IF
THERE ARE CLINICAL RESEARCH, I
WOULD SAY FOR MOST OF THESE
THINGS YOU STILL NEED TO DO SOME
MANUAL CURATION TO MAKE SURE IT
MEANS WHAT YOU THINK IT MEANS.
I THINK REPORTER AND ALL THESE
SEARCHES AND SEARCHING TOOLS ARE
GOOD TO GET YOU A FIRST
APPROXIMATION OF WHAT'S THERE.
IF YOU WANT TO GO MORE DEEPLY
YOU HAVE TO DOWNLOAD MANICALLY
AND DO IT.
WE DON'T DO IS THAT LEVEL FOR
ALL OF THE GRANTS, FOR ALL OF
THE AREAS, AND PART IS SO I DO A
LOT OF THIS KIND OF TRYING TO
UNDERSTAND PORTFOLIO THINGS, AND
EVERYBODY HAS SORT OF A
DIFFERENT NEED AND DIFFERENT --
IT'S REALLY SPECIFIC TO THE
QUESTION YOU'RE TRYING TO ANSWER
IN A LOT OF THESE CASES.
I WOULD -- SEARCH TERMS ARE
POWERFUL.
LOOK CLOSELY AND THINK WHAT ARE
THE QUESTIONS YOU'RE TRYING TO
ANSWER.
THANK YOU.
WE HAVE A COUPLE QUESTIONS FROM
THE AUDIENCE.
>> MICHAEL PERLMUTTER, CEREBRAL
PALSY, A CO-WORKER IS SORRY HE
COULD NOT MAKE IT TODAY.
MY QUESTION IS SPECIFICALLY FOR
YOU.
HOW DO YOU IDENTIFY THE
ORGANIZATIONS YOU LAUNCH
PARTNERSHIPS WITH AND WHAT DOES
THE PROCESS LOOK LIKE?
IT'S SOMETIMES AWKWARD TO
APPROACH AN ORGANIZATION THAT IS
MAYBE PERCEIVED AS COMPETING FOR
FUNDING WITH YOU.
>> THANK YOU FOR THE QUESTION.
WE'VE ESTABLISHED PARTNERSHIPS
IN A NUMBER OF WAYS, AND THE
PARTNERSHIP WITH ADDF PREDATES
ME, SO THAT WAS AN INTERACTION,
A PERSONAL CONNECTION BETWEEN
FOLKS IN OUR TWO ORGANIZATIONS.
IN THE CASE OF THE DIGITAL TOOLS
PARTNERSHIP WE WANTED TO DO A
PARTNERSHIP IN THE ALS FIELD,
PARTICULARLY INTERESTED IN BEING
ABLE TO FIND ASSESSMENTS THAT
WOULD SPAN THAT WHOLE ENTIRE
SPECTRUM.
SO WE WERE ABLE TO REACH OUT TO
THE ALS ASSOCIATION AND THEY
WERE EAGER TO JOIN IN WITH US.
SO SOMETIMES IT COMES FROM
WANTING TO MEET A SPECIFIC GOAL
IN REACHING OUT TO A POTENTIAL
PARTNER ORGANIZATION.
SOMETIMES THEY APPROACH US AND
EVOLVE ORGANICALLY.
>> WE HELD A MEETING ON DIGITAL
TOOLS, THE FTD WAS CREATING
THEIRS, SOMETIMES HAD
OVERLAPPING PATIENT POPULATIONS
SO AROSE FROM THAT AND THE ALS
ASSOCIATION WAS INVITED TO THAT
SO WHEN WE ORGANIZE THE OUR
MEETINGS INVITED THOSE FOLKS TO
COME.
AND BE PART OF THE LEARNINGS AND
DISCUSSION.
>> AMERICAN EPILEPSY FOUNDATION.
CURIOUS ON THE ROLE OF PEOPLE
WITH LIVED EXPERIENCE IN THE
SETTING OF YOUR RESEARCH AGENDA
OR IN THE REVIEW OF YOUR
RESEARCH GRANTS OR SELECTION OF
THOSE RESEARCHERS ENGAGED IN ANY
OF OUR FELLOWSHIP PROGRAMS.
>> YES, IN OUR REVIEW PANELS, WE
DO INCLUDE IN ALL OF THEM
PATIENT ADVOCATES.
WE TRY TO HAVE AT LEAST ONE,
PREFERABLY TWO.
THE PARKINSON'S FOUNDATION HAS A
WHOLE SEPARATE DEPARTMENT THAT
RECRUITS UNTRAINED PATIENT
ADVOCATES YOU WHO TO PARTICIPATE
IN THE REVIEW PROCESS, MEET WITH
THEM ONCE OR TWICE BEFORE REVIEW
PANELS, MAKE SURE THEY REMEMBER
HOW TO ACCESS SUBMISSION
PLATFORM.
AND I USUALLY MEET WITH THEM TO
MAKE SURE THAT THEY HAVE THE
MATERIALS, THAT THEY READ
THROUGH PROPOSALS BUT DO INVOLVE
THEM IN ALL OF OUR REVIEW
PANELS.
WE TRY FOR THEM TO REVIEW AS
MANY OF THE PROPOSALS THAT THEY
CAN IN THE PANEL.
THEY USUALLY DON'T GET TO REVIEW
ALL OF THEM.
BUT THEY DO HAVE AN ACTIVE ROLE.
AND EVEN IF THEY HAVEN'T READ
ALL THE PROPOSALS, WE MAKE SURE
THAT IN ALL THE REVIEW PANELS
WHEN THEY HEAR THE DISCUSSION
THEY ARE ASKED ABOUT WHAT THEY
THINK.
AND SOMETIMES, YOU KNOW, WHEN
REVIEWERS ARE DISCUSSING
SOMETHING AND THEY HEAR THE
PATIENT ADVOCATE, EITHER A
PERSON WITH PARKINSON'S OR
CAREGIVER, IT REALLY CHANGES,
YOU KNOW, HOW THEY SEE A
PROPOSAL WHEN THEY THINK, YOU
KNOW, IT'S NOT REALLY RELEVANT
OR THEY HAD A LOT MORE TO SAY
THAN THEY THOUGHT THEY WOULD.
>> MANISH, DO YOU WANT TO ANSWER
THE QUESTION ONLINE?
DID YOU HEAR IT?
>> CAN YOU REPEAT IT PLEASE?
I COULDN'T QUITE HEAR THAT.
>> THE QUESTION WAS ABOUT THE
INCLUSION OF PEOPLE WITH LIVED
EXPERIENCE IN THE DECISIONS
AROUND WHAT IS THE OVERARCHING
GRANT PORTFOLIO AS WELL AS
DECISIONS ON SPECIFIC GRANTS.
>> WE'RE A RESEARCH FOCUSED
ORGANIZATION.
IN OUR PARADIGM, AS I'VE
MENTIONED IN THE PRESENTATION,
WE HAVE THE INDEPENDENT REVIEW
COMMITTEE AND WE HAVE SCIENTISTS
THERE.
SO WE HAVE TAKEN INTEREST FROM
PEOPLE WITH LIVED EXPERIENCE
WHEN IT COMES TO CORE
FACILITIES, AND IN
COMMUNICATIONS, IN TAKING
DECISIONS ON GRANTS THAT IS AN
AREA WHERE WE HAVE RELIED
ENTIRELY ON PEOPLE ONE WOULD
CONSIDER AS EXPERTS IN THE
SUBJECT MATTER AT HAND.
>> THANK YOU, I'M GOING TO CHIME
IN AND DEFER.
PART OF OUR FOCUS, FOR EXAMPLE,
OF THE CONNECTION TO ALS IS
BECAUSE WE HAVE MANY PEOPLE ON
THE BOARD AND RESEARCH
COMMITTEES THAT DECIDE WHICH
GRANTS WE FUND, TAKE REVIEWER
FEEDBACK AND MAKE FINAL
DECISIONS.
A LOT OF FOLKS ARE FROM GENETIC
FAMILIES, DON'T HAVE MUCH LIVED
EXPERIENCE ABOUT HAVING EITHER
FTD OR ALS OR A COMBINATION
MANIFEST IN THEIR FAMILIES.
WE DON'T BRING THEM IN AS
REVIEWERS BUT IN DECISIONS
AREN'T WHERE OUR FUNDING
PORTFOLIO LIES.
>> I'LL JUST ADD IN OUR PILOT
GRANTS THE MOST RECENT FUNDING
STREAM IS A PILOT GRANT THAT
SPEAKS SPECIFICALLY TO
INTERVENTIONS FOR IMPROVING
QUALITY OF LIFE FOR PEOPLE WITH
FTD IN THEIR FAMILIES SO WE HAVE
A FUNDING STREAM THAT IS
SPECIFICALLY DIRECTED TO THEIR
NEEDS.
WE ALSO OFFER OPPORTUNITIES FOR
RESEARCHERS AND PEOPLE WITH
LIVED EXPERIENCE TO ENCOUNTER
ONE ANOTHER AND LEARN FROM ONE
ANOTHER.
SO, FOR EXAMPLE, WE HAVE DONE
FOR THE LAST SEVERAL YEARS A
NETWORKING EVENT AT THE SOCIETY
FOR NEUROSCIENCE MEETING, AND
THIS IS A SATELLITE EVENT.
SO WE ARE ABLE TO INVITE PEOPLE
FROM OUR COMMUNITY WHO CAN COME
IN AND TALK TO THE RESEARCHERS,
GET TO MEET THEM, VICE VERSA.
AND AT OUR ANNUAL EDUCATION
CONFERENCE THIS PAST YEAR, WHICH
IS A MEETING THAT IS
SPECIFICALLY FOR PEOPLE WITH FTD
AND THEIR FAMILIES, A CHANCE FOR
THEM TO GET MUTUAL SUPPORT, WE
HAD A PANEL THAT FEATURED THREE
OF OUR FUNDED RESEARCHERS.
AND THEY WERE ROCK STARS.
THEY DID A GREAT JOB.
THEY TOOK QUESTIONS FROM THE
AUDIENCE, AND IT WAS A WONDERFUL
OPPORTUNITY FOR PEOPLE TO SEE
THE RESEARCHERS HAVE A HUMAN
FACE AND FOR RESEARCHERS TO
UNDERSTAND WHAT FAMILIES GO
THROUGH.
>> AND I'D LIKE TO JUST ADD A
LITTLE BIT OF COLOR TO THE
QUESTION THAT PENNY AND DEBRA
ANSWERED ABOUT HOW YOU APPEAL TO
ORGANIZATIONS THAT MIGHT
CONSIDER YOU A COMPETITOR FOR
FUNDING.
WHEN WE FIRST ESTABLISHED FARA
WE KNEW THE MUSCULAR DYSTROPHY
ASSOCIATION WITH OUR DISEASE AS
ONE OF ITS 42 DISEASES.
WE KNEW NATIONAL ATAXIA
FOUNDATION WITH IT.
WE SAT DOWN WITH BOARDS OF
DIRECTORS AND TOLD THEM WE'RE
NOT HERE TO COMPETE, WE'RE HERE
TO COLLABORATE, WE CO-FUNDED
GRANTS, SHARED REVIEWS AND
PARTNERSHIPS HAVE LASTED THROUGH
THE 25 YEARS OF OUR EXISTENCE
AND WE'VE FUNDED MILLIONS OF
DOLLARS OF RESEARCH TOGETHER.
>> I'M NOT SEEING OTHER
QUESTIONS.
WE HAVE A FEW MORE MINUTES.
OH, WE DID HAVE ANOTHER ONE.
DR. KOROSHETZ?
>> I WAS WONDERING IF MAYBE SOME
OF YOU COULD TALK A LITTLE BIT
ABOUT KIND OF THE ORIGINS OF
YOUR FOUNDATION AND HOW YOU
PROGRESSED OVER THE YEARS.
CERTAINLY FTD AND PARKINSON'S
FOUNDATIONS HAVE BEEN AROUND FOR
A WHILE, BUT A LOT OF THE
ORGANIZATIONS HERE, SOME ARE
YOUNGER AND MIGHT BENEFIT FROM
KIND OF THE HISTORY AND WHAT
THINGS ALLOWED YOU TO GROW WHEE
YOU ARE NOW.
>> MANISH, DID YOU HEAR THAT?
>> YES.
>> DO YOU WANT TO TAKE THAT
FIRST?
>> SURE.
WE LAUNCHED IN 2013, THEY ARE
OFTEN LAUNCHED BY SOMEONE WHO
HAS BEEN PERSONALLY AFFECTED.
SO OUR FOUNDER THEN, THIS IS
PUBLIC KNOWLEDGE, LOST HIS
FATHER TO ALS.
AND THAT'S WHAT MOTIVATED HIM TO
DO SOMETHING ABOUT THE DISEASE
AND LAUNCHED THE FOUNDATION.
BRIEF HISTORY, BASED OUT OF
COLUMBIA UNIVERSITY, THE IDEA
FUNDS WERE FOR ANY SCIENTIST
AROUND THE WORLD WITH A GOOD
IDEA BUT WE WERE LEVERAGING
COLUMBIA'S INFRASTRUCTURE.
AROUND 2015 WE REALIZED IF WE
WANTED TO BE NIMBLE AND BEING
FAIR TO COLUMBIA UNIVERSITY, A
BIG UNIVERSITY INFRASTRUCTURE IS
NOT GEARED TOWARDS QUICK
DECISION MAKING.
SO WE SPUN OUT AND BECAME AN
INDEPENDENT NON-PROFIT AT THAT
POINT.
AND THEN WE HAVE BEEN ABLE TO
GROW GRADUALLY.
ONE OF THE KEYS FOR US HAS BEEN
WE HAVE ALWAYS TRIED TO THINK
DIFFERENTLY ABOUT HOW WE WANT TO
APPROACH THE CHALLENGES FACING
THE FIELD, IDENTIFYING KEY
BARRIERS IN OUR PRESENTATION AND
TRYING TO ADDRESS THEM.
THAT HAS ALLOWED US TO ESTABLISH
A POSITION OF CREDIBILITY IN THE
BROADER COMMUNITY, AND THAT HAS
ALLOWED US TO THEN GROW.
>> THANK YOU.
SPEAKING FOR THE ASSOCIATION FOR
FRONTOTEMPORAL DEGENERATION
FOUNDED BY HELEN ANN COMSTOCK, A
CAREGIVER FOR HER HUSBAND,
STARTING WITH A $1,000 DONATION,
15 YEARS AGO.
MY BOSS IS GOING TO GET MAD IF I
DON'T REMEMBER THE DETAILS.
SHE'S BEEN ACTIVE IN THE
ALZHEIMER'S ASSOCIATION WHICH IS
AN INCREDIBLE ORGANIZATION.
BUT WHAT SHE FELT VERY DEEPLY IS
THAT THE NEEDS OF PEOPLE WITH
FTD ARE DIFFERENT, AN EARLIER
ONSET DEMENTIA, SYMPTOMS CAN BE
DIFFERENT.
IF YOU'RE 50 AND DEALING WITH
BEHAVIORAL AND COGNITIVE -- NOT
MEMORY PROBLEMS BUT BEHAVIORAL
OR LANGUAGE OR MOTOR PROBLEMS
WITH SOMEBODY WHO IS DYING OF A
FATAL NEURODEGENERATIVE DISEASE
YOUR NEEDS AS CAREGIVER, OFT
WITHIN YOUNG KIDS AT HOME, ARE
DIFFERENT THAN A 70-YEAR-OLD
CARING FOR A HUSBAND WITH MEMORY
LOSS THAT'S VERY WELL UNDERSTOOD
BY THE NEUROLOGY COMMUNITY.
HELEN FOUNDED FTD WITH A
THOUSAND DOLLAR DONATION, A
LONGSTANDING VOLUNTEER, FOUND A
GROUP OF LIKE-MINDED FOLKS,
FOUND AMAZING RESEARCHERS WHO
UNDERSTOOD AND WERE COMMITTED TO
MAKING A DIFFERENCE IN THE SPACE
AND IT'S GROWN OVER MANY, MANY
YEARS.
WE HAVE A STAFF OF 45 PEOPLE
RIGHT NOW.
DO YOU WANT TO ANSWER ON BEHALF
OF PARKINSON'S FOUNDATION?
>> I KNOW THE FOUNDATION AS IT
IS NOW CALLED, PARKINSON'S
FOUNDATION, WAS RESULT OF A
MERGER FROM PARKINSON'S DISEASE
FOUNDATION THAT WAS IN NEW YORK
CITY AND I THINK IT WAS
INTERNATIONAL PARKINSON'S
FOUNDATION BASED IN MIAMI.
SO, I THINK THE TWO FOUNDATIONS
REALIZED THEY WERE BETTER
TOGETHER THAN BY THEMSELVES.
AND THEY DECIDED TO MERGE BACK
IN 2016, THAT'S WHEN THE NOW CEO
WAS HIRED.
HE REALLY DID A TREMENDOUS JOB
OF BRINGING TWO FOUNDATIONS
TOGETHER AND MAKING THEM INTO A
COHESIVE FOUNDATION THAT WORKS
PRIMARILY REMOTE.
WE WERE IN TUNE BEFORE THE
PANDEMIC.
SO, IT WAS REALLY EASY FOR US TO
BEAR THE PANDEMIC IN THAT WAY.
AND JOHN PREVIOUSLY WORKED AT
CYSTIC FIBROSIS FOUNDATION, THAT
I THINK EVERYONE KNOWS BECAUSE
OF THEIR INCREDIBLE SUCCESS IN
BRINGING DRUGS TO MARKET.
HE TOOK EVERYTHING HE HAD
LEARNED WORKING AT THE CYSTIC
FIBROSIS FOUNDATION, KNOWING
THAT PARKINSON'S FOUNDATION IS
NOT CYSTIC FIBROSIS, IT'S A MORE
COMPLEX DISEASE.
THE STRATEGIES WERE NOT GOING TO
WORK FOR PARKINSON'S BUT HE
MANAGED, YOU SAW THE RESULTS IN
THE SLIDES, A LOT OF THINGS, THE
FOUNDATION TOOK OFF SINCE HE
TOOK OVER IN 2016, IN TERMS OF
FINANCIALLY AND PERSONNEL.
WE'VE EXPANDED NOT ONLY ON THE
RESEARCH SIDE BUT ALSO THE
CLINICAL SIDE WITH CLINICAL
WORK.
ALSO ALL THE WORK WE FUND IN
EDUCATION AND THE CARE AND
THINGS WE DO FOR CAREGIVERS.
SO THE FOUNDATION AS IT IS NOW,
IT'S REALLY THE RESULT OF GREAT
MANAGEMENT AND THE PEOPLE THAT
WORK THERE.
RIGHT NOW IT'S AROUND 150.
>> I SAY WITH A RECOGNITION
THERE ARE OTHER COMMUNITIES
AHEAD OF THE HUNTINGTON'S
DISEASE COMMUNITY, WHEN IT COMES
TO HAVING DISEASE-MODIFYING
THERAPIES, OR LEVELS OF
TRANSFORMATIVE CARE TOOLS FOR
THEIR PATIENT POPULATIONS.
TODAY YOU'RE GOING TO HEAR FROM
MELISSA KENNEDY, TALKING ABOUT A
BREAKTHROUGH IN TREATMENT OF
RETT SYNDROME.
YOU'LL HEAR FROM RON BARTEK
TALKING ABOUT THE RECENT
APPROVAL OF A DRUG FOR
FRIEDRICH'S ATAXIA.
AND TWO SPEAKERS WHO FOR
DIFFERENT REASONS ARE UNABLE TO
BE HERE BUT NEIL THAKUR TALKING
ABOUT STRATEGIES FOR ALS AND
FOLLOWED BY DR. TIM MILLER FROM
WASHINGTON UNIVERSITY, WHO HAS A
RECORDED PRESENTATION BUT IS
GOING TO JOIN LIVE FOR THE
CONVERSATION.
EACH HAS TAKEN ADVANTAGE OF
ACCELERATED APPROVAL.
THERE'S A LOT OF MAGIC AND LUCK
AND DETERMINATION IN THE DRUG
PROCESS.
WE DON'T HAVE CORPORATE
REPRESENTATIVES IN THE ROOM,
ANOTHER PART OF THE PARTNERSHIP
THAT MAKES THIS POSSIBLE.
BUT FROM THE IDENTIFICATION OF
POTENTIAL STRATEGY FOR DRUG
DEVELOPMENT TO THE PRE-CLINICAL
WORK, MOUSE MODELS, TO THE
SAFETY AND EFFICACY TRIALS,
PHASE 1, 2, 3, AND THEN IF
YOU'RE ABLE TO GET TO 4 THROUGH
THE POST MARKETING APPROVAL IT'S
A REALLY LONG PROCESS.
WE ALL KNOW THAT.
ACCELERATED APPROVAL CAN PROVIDE
NOT A SHORTCUT BUT MAYBE A FAST
TRACK FOR SPECIAL PROGRAMS ABLE
TO SHOW ABILITY TO INFLUENCE
DISEASE PROGRESSION AND HAVE
MEANINGFUL IMPACT ON OUR
FAMILIES.
EARLY.
WE LEARN FROM THIS.
THAT'S WHAT TODAY'S SESSION IS
ALL ABOUT.
WE'RE GOING TILL 4:00, 4:10, TO
MAKE SURE WE HAVE TIME FOR
WALTER TO TAKE US HOME TODAY.
EACH SPEAKER WILL SHOWCASE
STORIES IN DRUG APPROVAL AND
WE'LL HAVE GROUP CONVERSATION.
I'LL TURN IT OVER TO MELISSA TO
GET US GOING.
THANKS, EVERYONE.
>> IT'S AN HONOR TO BE HERE
TODAY.
WHICH MIC IS BEST?
BOTH OF THEM, OKAY.
SEVERAL COMMENTS HAVE BEEN MADE.
I HAVE THE DISTINCT HONOR OF
SERVING EVERY DAY AS THE CEO OF
INTERNATIONAL RETT SYNDROME
FOUNDATION.
I'VE ONLY BEEN IN THIS ROLE FOR
SIX YEARS.
I SAY "ONLY" BECAUSE THE DRUG
DEVELOPMENT PROCESS EVEN
ACCELERATED IS EXCRUCIATINGLY
LONG AND PAINFUL.
I'M ONLY HERE RIGHT NOW BECAUSE
OF THE DETERMINATION AND HARD
WORK OF BOARD MEMBERS OF IRSF
MAKING CRITICAL DECISIONS IN
2010.
I'M ONLY HERE BECAUSE OF THE
VERY BRAVE PATIENT COMMUNITY AND
CAREGIVER COMMUNITY THAT
PARTICIPATED IN CLINICAL TRIALS,
I FEEL LIKE AN IMPOSTOR WHO CAME
IN AT THE END OF A GREAT STORY.
LIKE MANY RARE DISEASE
FOUNDATIONS, OURS HAD VERY
HUMBLE BEGINNINGS 40 YEARS AGO,
198 3, KITCHEN TABLE OF KATHY
HUNTER, A MOM OF A BEAUTIFUL
YOUNG GIRL DIAGNOSED WITH RETT
SYNDROME, THE KITCHEN TABLE IS
NOT FAR FROM HERE, SO IT'S AN
HONOR TO BE HERE WITH YOU.
OVER THE 40-YEAR PERIOD OF TIME
OUR BOARD HAS GROWN AND MATURED.
WE NOW HAVE A BOARD THAT IS MADE
OF CAREGIVERS, PARENTS, AND
AUNTS, UNCLES, SCIENTISTS,
CLINICIANS, ALSO RECENTLY
BIOTECH INVESTORS, HELPFUL IN
THE NEW PHASE.
WE HAVE A DUAL MISSION OF
ACCELERATING MEANINGFUL AND
POTENTIALLY HELPFUL RESEARCH,
WHILE SUPPORTING, EDUCATING,
EMPOWERING AND ADVOCATING FOR
FAMILIES.
OUR RESEARCH IS STRAIGHTFORWARD,
MULTIPLE SHOTS ON GOAL, AND NO
ONE GETS LEFT BEHIND.
WE HAVE THREE PRONGS TO THE
RESEARCH STRATEGY.
THIS IS REALLY IMPORTANT BECAUSE
THE DEBUT DISCOVERY, THE
COMPOUND THAT WAS JUST APPROVED,
IS A PART OF THIS.
IT'S A SUCCESSFUL STORY FROM A
PIECE OF THIS.
WE FUND BASIC RESEARCH, THAT'S
THE CRITICAL RESEARCH.
RETT IS THE MOST SEVERE -- ONE
OF THE MOST SEVERE
NEURODEVELOPMENTAL DISORDERS
THAT GIRLS CAN HAVE, IT'S NOT
NEURODEGENERATIVE.
BOYS CAN HAVE IT AS WELL.
PREVALENCE IS ABOUT 1 IN 10,000
BIRTHS.
DR. ZOGBE IDENTIFIED THE GENE
THAT CAUSES RETT SYNDROME, WHEN
THERE'S A MUTATION OR DELETION,
MECP2 GENE DISCOVERED IN 1999.
SINCE 1999 WE'VE BEEN DOING A
LOT OF WORK TO FURTHER
UNDERSTAND MECP2 BUT DON'T
UNDERSTAND IT WELL ENOUGH.
SO AS A FOUNDATION WE INVEST IN
CONTINUING TO DEEPEN OUR
UNDERSTANDING OF WHATTING IT --
WHAT IT IS AND HOW IT WORKS
WHILE INVESTING IN POTENTIAL
CURATIVE STRATEGIES, GENE
THERAPY AND OTHER GENETIC
APPROACHES.
SIMULTANEOUSLY, WE INVEST IN
PIPELINE DEVELOPMENT,
IDENTIFYING MOLECULES, SMALL
MOLECULES NOT INTENDED
NECESSARILY TO BE A CURE FOR
RETT SYNDROME BUT WOULD HAVE A
MEANINGFUL EFFECT ON DOWNSTREAM
TARGET INTENDED TO OVERALL
IMPROVE THE QUALITY OF LIFE BY
REDUCING MANY, MANY SYMPTOMS OF
RETT SYNDROME, AND SPOILER
ALERT, THIS IS WHAT DEBUT IS,
THE COMPOUND THAT WAS RECENTLY
APPROVED BY THE FDA.
AND FINALLY WE ALSO INVEST
HEAVILY IN A CLINICAL TRIAL
INFRASTRUCTURE.
WE SUPPORT CENTER OF EXCELLENCE
NETWORK.
WE SUPPORT REGISTRY AS WELL AS
CONTINUAL WORK AND OUTCOME
MEASURES.
IT IS DAYBUE IS THE FIRST
APPROVED TREATMENT FOR RETT
SYNDROME, MARCH 10 OF 2023, JUST
ABOUT A MONTH AFTER RON'S, WHICH
WAS REALLY EXCITING.
IT HAPPENED BECAUSE OF REALLY
HARD WORK, BECAUSE BRILLIANT
PEOPLE WORKED HARD FOR MANY
YEARS, IT ALSO HAPPENED BECAUSE
WE WERE REALLY LUCKY AND THERE
WAS SERENDIPITY INVOLVED.
THERE'S BEAUTY IN THAT THAT I'LL
TALK ABOUT.
IT IS AS I SAID A SMALL MOLECULE
INTENDED TO HAVE IMPACT ON
DOWNSTREAM TARGETS OF THE MECP2
GENE.
IN GENERAL I CAN TALK ABOUT
SWEET ANECDOTES BECAUSE WE ARE
HAVING MORE AND MORE PEOPLE WHO
ARE NOW TAKING ADVANTAGE OF
DAYBUE.
SOME FRANKLY IT DOESN'T DO A LOT
FOR.
THERE ARE OTHERS WHO ARE SEEING
SUCH A PROFOUND IMPACT, YOUNGER
INDIVIDUALS, THAT IT'S BEEN
CALLED DISEASE MODIFYING FOR
THEM.
IT IS NOT A CURE BUT IT HAS
GIVEN US A LOT OF HOPE.
INTERESTINGLY DAYBUE IS THE
TRADE NAME FOR A MOLECULE FIRST
BROUGHT TO THE ATTENTION OF THE
RETT SYNDROME FOUNDATION,
TROFINETIDE.
HE WAS WORKING WITH DoD AND
SAW THIS MOLECULE COME ACROSS
HIS DESK AS POTENTIAL TREATMENT
FOR TRAUMATIC BRAIN INJURY.
HE LOOKED AT THE MOLECULE AND
THOUGHT I DON'T KNOW ABOUT TBI
BUT I THINK THIS MIGHT WORK FOR
RETT SYNDROME, BROUGHT IT TO THE
ATTENTION OF OUR FOUNDATION,
THIS WAS IN 2010 TO 2012.
OUR FOUNDATION INVESTED IN THE
MOLECULE, IN THE EARLY CLINICAL
TRIAL OF THAT MOLECULE, UNTIL IT
WAS BROUGHT TO A POINT IN PHASE
3, THAT'S FAR BEYOND WHAT A RARE
DISEASE FOUNDATION CAN SUPPORT.
ACADIA PHARMACEUTICALS FUND THE
PHASE 3 TRIALS AND IT WAS A
SUCCESS.
I'M VERY HAPPY TO BE ABLE TO
SHARE THAT WITH YOU TODAY.
IT'S THEORIZED TO WORK BY
REDUCING INFLAMMATION, THE
MECHANISM OF ACTION IS CLEARLY
NOT DESCRIBED AND DEFINED.
IN TERMS OF THE CLINICAL TRIAL
THERE WERE TWO CO-PRIMARY
ENDPOINTS, ONE CALLED THE RETT
SYNDROME BEHAVIORAL
QUESTIONNAIRE, RFBQ,
CAREGIVER-REPORTED
QUESTIONNAIRE.
OTHER IS CGII, CLINICIAN
ASSESSING GLOBAL IMPROVEMENT.
THERE WAS STATISTICALLY
SIGNIFICANT IMPROVEMENT ON BOTH
SCALES COMPARED TO PLACEBO.
IT WAS BECAUSE OF THAT THAT A
DECISION WAS MADE AS WELL AS
MANY OTHER THINGS, DECISION TO
APPROVE FOR TREATMENT.
YOU CAN SEE THERE ARE A GENERAL
SUBSCALE OF THE RSBQ, IMPROVED
BREATHING, HAND BEHAVIORS FOR
THOSE WHO MIGHT NOT BE AWARE,
RETT SYNDROME HAS A CLASSIC
MOVE, REPETITIVE HAND MOVEMENT
AND INDIVIDUALS WITH RETT ARE
ALMOST ALL UNABLE TO
MEANINGFULLY USE THEIR HANDS.
FACE MOVEMENTS, BODY ROCKING,
EXPRESSIONLESS FACE, NIGHTTIME
BEHAVIORS, SLEEPING IS A PROBLEM
FOR FAMILIES WHO HAVE A CHILD
WITH RETT SYNDROME.
THERE'S A LOT OF FEAR AND
ANXIETY THAT IS ASSOCIATED WITH
RETT, ABILITY TO WALK,
INDIANENEDLY -- INDEPENDENTLY
STAND AND MOVE AROUND.
I'LL TALK ABOUT HOW WE
INCORPORATED THE FAMILIES INTO
THE PROCESS AND HOW WE EMBED THE
FAMILY VOICE IN ALL OF THIS.
SUCCESSFUL DRUG VALUE.
HAPPENS BECAUSE IT'S A BEAUTIFUL
COLLABORATION BETWEEN SCIENTISTS
AND CLINICIANS AND INDUSTRY'S
ADVOCACY AND FAMILIES.
WE DID A FEW THINGS IN THE YEARS
LEADING UP TO THE FDA APPROVAL.
WE DID HOLD AN EXTERNALLY LED
MEETING IN MARCH OF 2020, A VERY
SUCCESSFUL MEETING, TIMING WAS
PERFECT.
OVER THE NEXT YEAR THE FDA
REVIEWED TROFINETIDE FOR
POTENTIAL APPROVAL AND HAD THE
EXTERNALLY LED PATIENT-FOCUSED
DRUG DEVELOPMENT MEETING REPORT
AVAILABLE AS PART OF THE REVIEW.
WE LAUNCHED WHAT WE CALL RETT
RESEARCH READY, OUR ATTEMPT TO
HELP FAMILIES BECOME RESEARCH
PARTNERS, LIVES ON OUR WEBSITE,
TEACHES FAMILIES WHAT
PARTICIPATION IN CLINICAL
RESEARCH LOOKS LIKE AND ALSO
INCORPORATION MY TRIAL FINDER SO
FAMILIES CAN FIND TRIALS CLOSE
TO THEM.
WE'VE LAUNCHED CLINICAL TRIAL
COMMITTEE WHICH IS A GROUP OF
KOLs THAT ADVISE INDUSTRY ON
PROTOCOL DESIGN AND OTHER
THINGS, AND WE HAVE FAMILIES
THAT HAVE A SEAT AT THAT TABLE.
SO THEY ARE PARTICIPATING IN THE
CONVERSATION WITH INDUSTRY AND
WITH OUR CLINICIANS AND KOLs
WHEN PROTOCOL DESIGN IS
DISCUSSED.
I'M GOING TO STOP THERE SO WE
HAVE TIME FOR EVERYBODY ELSE,
BUT I REALLY APPRECIATE THE
OPPORTUNITY TO SPEAK WITH YOU
TODAY.
THANK YOU.
>> I'M STILL RON BARTEK.
I'M HONORED TO BE A MEMBER OF
THIS PANEL AND REALLY THRILLED
TO BE A MEMBER OF ANYTHING
CALLED A SUCCESS STORY PANEL.
FOR THE FIRST TIME IN 25 YEARS,
YEAH.
SO ...
I'LL GET STARTED ON THAT
EMOTIONAL NOTE.
I WANT TO TELL YOU JUST ENOUGH
ABOUT FRIEDRICH'S ATAXIA SO KNOW
WHAT YOU DRUG SEEMS TO BE DOING
AND HOW.
IT'S A RARE RECESSIVE TRAIT,
GENETIC NEUROMUSCULAR DISEASE,
5,000 PEOPLE IN THE U.S. ARE
AFFECTED.
AND MAYBE 20,000 WORLDWIDE.
RESULTS FROM A TRINUCLEOTIDE
EXPANSION AND THE FIRST INTRON
OF A GENE.
IF THE MUTATION IS IN AN INTRON
YOU WOULDN'T EXPECT IT TO AFFECT
A PROTEIN, RIGHT?
IT'S THE EXONS THAT GENERATE THE
PROTEIN.
BUT IN THIS CASE, THE EFFECT OF
THE INTRONIC EXPANSION UP TO A
THOUSAND OR SO, 1500 GAA
REPEATS, IS TO PARTIALLY SILENCE
THAT GENE THROUGH MECHANISMS
THAT WE THINK WE NOW FULLY
UNDERSTAND.
SO, WHAT YOU DO IS YOU REDUCE,
PARTIALLY SILENCING EXPRESSION
OF PROTEIN, REDUCING PROTEIN
EXPRESSION FROM 100% IN OUR
NORMALS TO ABOUT 10 TO 15% IN
OUR PATIENTS.
GOOD NEWS HERE TOO THOUGH, THEIR
PARENTS ARE CARRIERS OF THAT
MUTATION, SO THEY ARE ONLY
GETTING 40 TO 60% OF THAT
PROTECTION PROTEIN, AND THEY ARE
COMPLETELY HEALTHY.
THAT'S THE TARGET SET THAT WE
STARTED WITH.
AND WHAT'S THE IMPACT OF THOSE
LOW LEVELS OF PROTEIN?
WELL, IN TWO WORDS,
MITOCHONDRIAL DYSFUNCTION.
MOST OF YOU KNOW THAT THE
MITOCHONDRIA ARE THE POWER
PLANTS OF ALL OF OUR CELLS,
RESPONSIBLE FOR PRODUCING ATP,
THE CURRENCY OF ENERGY FOR OUR
CELLS.
AND ON THE SIDE PRODUCE WATER.
NET RESULT OF HEALTHY
MITOCHONDRIA IS ATP AND WATER.
THE FUNCTION OF THING PROTEIN IS
TO GENERAL -- GENERATED IN THE
NUCLEUS, GOES INTO CYTOPLASM,
BINDS WITH IRON, KEEPS IRON IN
PROPER STATE TO MOVE TO
MITOCHONDRIA MATRICES, TO
PRODUCE DOWN AT THE END THE
FIFTH COMPLEX, YOU GET ATP AND
WATER.
IF YOU HAVE A SHORT SUPPLY OF
THE PROTEIN IT DOESN'T BIND WITH
ENOUGH IRON TO JOIN WITH THE
IRON SULPHUR CLUSTERS, SO IT
FORMS FERROUS OXIDE, LOSES --
INSTEAD OF ESCORTING ELECTRONS
WITH THE CLUSTERS ALONG THE
MATRICES THEY ESCAPE AND FORM
RADICALS.
NET RESULT OF LOW LEVELS IS
INCREASED OXIDATIVE STRESS,
INCREASED INFLAMMATION,
DECREASED ENERGY PRODUCTION.
IT'S A DOUBLE WHAMMY IN THIS
CASE BECAUSE AS THE LOW LEVELS
OF FURTAXIN ARE CAUSING
INFLAMMATION, GREATER OXIDATIVE
STRESS, NATURAL DEFENSES OF A
HEALTHY CELL NAMELY Nrf2
TRANSCRIPTION FACTOR, ITS
RESPONSIBILITY IS ACTIVATE GENES
THAT PRODUCE THE TO COMBAT
OXIDATIVE STRESS, COMBAT
INFLAMMATION.
YOU EXPECT LOW LEVELS OF
FURTAXIN, MORE NRF2.
BOLOGNA.
COUNTER INTUITIVELY, AS YOU
DROPPED FURTAXIN, THE NRF2
PATHWAY IS DEMOBILIZED.
LESS ENERGY, AND WE CAN'T RALLY
THE TROOPS OF OUR NORMAL
DEFENSES AGAINST THAT
INFLAMMATION AND OXIDATIVE
STRESS.
NET RESULT IT'S PROGRESSIVE,
DIAGNOSED BY 7 AND 15, IMPACTS
VISION, HEARING, SPEECH, SEVERE
SCOLIOSIS REGARDING SURGICAL
IMPLANTATION OF METAL RODS TO
KEEP THE SPINE STRAIGHT, MUCH
INCREASED RISK OF DIABETES AND
MOST CONDEMNING FACTOR IS HEART
CONDITION THAT LEADS TO
CONGESTIVE HEART FAILURE.
AND THE END OF YOUNG LIVES.
ENTER PHARMACEUTICALS.
NOW CALLED SKYCLARYS.
WHAT DOES IT DO?
WELL, IT MOVES INTO THE ARENA IN
WHICH WE'VE JUST DESCRIBED.
RISING STRESS AND INFLAMMATION.
AND LOW ENERGY.
THE MITOCHONDRIA ARE STRUGGLING
AND DYING, WHICH LEADS TO
APOPTOSIS, CELL DEATH.
AND THE ALERT GOES OUT THAT'S A
LITTLE MITOCHONDRION, BY THE
WAY, THE SQUIGGLY LINE TO THE
UPPER LEFT.
THEY ARE IN DISTRESS,
STRUGGLING.
THEY ARE NOT GETTING NORMAL
SUPPORT FROM NORMAL DEFENSES.
ENTER OMAV, MADE FROM FROM AN
ACID AVAILABLE IN VARIOUS
PLANTS.
MECHANISM OF ACTION IS TO
ACTUALLY REACTIVATE THE NRF2
PATHWAY, TO GENERATE DEFENSE,
NORMAL DEFENSES TO A LARGE
EXTENT.
AND IT WILL SEND THOSE
ACTIVATORS TO PRODUCE THE
DEFENSES AND PROTECT FIRST THE
MITOCHONDRIA, AND THEN THE WHOLE
CELL.
MORE ENERGY, LESS INFLAMMATION,
LESS OXIDATIVE STRESS, WHAT
CONVINCED US AND THE FDA THIS
DRUG WAS GOING TO WORK?
WHAT YOU SEE ON THE LEFT, LET'S
MAKE THIS WORK.
YOU SEE RIGHT THERE THESE ARE
THE DATA RESULTS OF PHASE 2
CLINICAL TRIAL.
ON THE TOP YOU SEE THE CONTROL
GROUP.
BOTTOM BLUE LINE YOU SEE THE
ACTIVE GROUP.
YOU SEE THESE DATA POINTS ARE ON
OUR FRIEDRICH'S ATAXIA RATING
SCHOOL, LIKE GOLF, LOW SCORE
WINS.
IF YOU'RE BEING EFFECTIVELY
TREATED, YOUR SCORE IS GOING
DOWN.
IF NOT EFFECTIVELY TREATED SCORE
GOES UP.
YOU CAN SEE THE DIFFERENCE
THERE, THE CONTROL GROUP IS
GETTING WORSE THROUGHOUT THE
YEAR, 48 WEEKS OF THE TRIAL.
THE ACTIVE GROUP IS ACTUALLY
IMPROVING.
THAT'S NEVER HAPPENED TO OUR
PATIENTS BEFORE.
THEY ACTUALLY IMPROVED.
IT WASN'T JUST THAT THEY WERE
DOING BETTER THAN THE CONTROL
GROUP.
THEY WERE ACTUALLY IMPROVING.
NET RESULT WAS 2.4-POINT
DIFFERENCE ON RATING SCALE.
SO, THE OTHER DATA POINT, AND
THIS IS DIRECT RESULT OF OUR
NATURAL HISTORY DATABASE, THAT
I'LL TALK MORE ABOUT LATER,
AFTER THAT PHASE 2 WAS DONE,
THAT ONE, THE REATTA
PHARMACEUTICALS GATHERED
PERFECTLY MATCHED COHORT OF 136
PATIENTS, COMPARED TO 136
PATIENTS IN THE OPEN LABEL
EXTENSION ACROSS THREE YEARS.
THEY SAW THE -- NOW, EVERYBODY
IN THE OPEN LABEL EXTENSION IS
ON DRUG.
SO THAT'S THIS BLUE LINE.
TOP LINE IS CAREFULLY MATCHED
136 PATIENTS ON NO DRUG, DIDN'T
HAVE ANY.
LOOK AT THE DIFFERENCE.
WHAT THAT REPRESENTS IS A 55%
SLOWING OF PROGRESSION IN OUR
DISEASE ACROSS THOSE THREE
YEARS.
IF YOU TOOK IT BACK FURTHER, TWO
YEARS OF THE PHASE 2 TRIAL, IT
WOULD BE MORE THAN 55% SLOWING
OF PROGRESSION.
SO THAT GOT US EXCITED.
AND LET'S TALK ABOUT HOW WE GOT
THERE.
HOW DID WE GET TO THAT KIND OF
RESULT?
STARTING IN 2009, GOING BACK TO
SUPPORTING BASIC RESEARCH.
WE SPENT THE FIRST FEW YEARS OF
OUR EXISTENCE SUPPORTING
PRIMARILY BASIC RESEARCH.
ONE OF THOSE BASIC RESEARCHERS
HAD FIRST IDENTIFIED IN 2009
THAT Nrf2 PATHWAY, AS
IMPORTANT, POTENTIALLY IMPORTANT
IN FA.
THAT WAS A GROUP IN FRANCE.
A FEW YEARS LATER 2013 A
CALIFORNIA GROUP SHOWED IT WAS
ADDRESSING THE PATHOPHYSIOLOGY
OF THE MOUSE.
WE HEARD FROM A FAMILY, TWO
PARENTS OF AN FA CHILD, CALLEDS
AND SAID -- THE WIFE SAID MY
HUSBAND HAS BEEN WORKING TANG
TANGENTALLY WITH A DRUG COMPANY,
REATA, I SEE IN TWO RESEARCH
STUDIES IN FRANCE AND CALIFORNIA
THAT THE NRF2 PATHWAY IS RELATED
TO FRIEDRICH'S ATAXIA, MAYBE WE
OUGHT TO LOOK INTO THAT.
OUR BEST CLINICIAN, MYSELF AND
EXECUTIVE DIRECTOR FLEW TO
DALLAS, PITCHED THE COMPANY,
THEY SAID, YEAH, MIGHT BE
INTERESTING BUT WE'RE WORKING ON
A DIFFERENT DISEASE.
SO THEY DEMURRED.
LATER THE NEXT YEAR, THEY CALLED
US BACK AND SAID, OKAY, WE'VE
RECONSIDERED.
WE THINK WE HAVE A CANDIDATE
THAT MIGHT BE OF INTEREST TO THE
FA COMMUNITY, LET'S START
MEETING.
THEY GOT TOGETHER WITH OUR BEST
CLINICIANS, FARA LEADERSHIP,
USED OUR NATURAL HISTORY STUDY
TO PLAN THEIR FIRST CLINICAL
TRIAL.
AND THEY USED THE NATURAL
HISTORY STUDY AND OUR BEST
CLINICIANS AND LEADERSHIP TO
DESIGN THAT CLINICAL TRIAL
AROUND ENDPOINTS THAT WE
DEVELOPED, AND HOLD THAT
CLINICAL TRIAL AT CLINICAL SITES
WE WERE SUPPORTING FOR YEARS.
WITH PHYSICIANS THAT KNEW OUR
PATIENTS AND OUR DISEASE.
TWO YEARS LATER FINISHED THAT
TRIAL, IT WAS SUFFICIENTLY
PROMISING RESULTS, THAT THEY
STARTED A SECOND CLINICAL TRIAL,
SAME CLINICAL SITES WE'VE BEEN
SUPPORTING FOR 15 YEARS.
IN 2020 AFTER FINISHING THAT
SECOND TRIAL, BEING VERY
ENCOURAGED BY THE RESULTS, WE
HAD MULTIPLE MEETINGS WITH THE
FDA.
FARA ALWAYS INVITED TO THESE,
PLAYING AN INTEGRAL ROLE IN THE
DISCUSSION.
2021, AFTER HEARING -- AFTER
MULTIPLE MEETINGS THE FDA
REVIEWERS WERE NOTE -- DID NOT
FIND DATA PERSUASIVE, WANTED US
TO DO ANOTHER PHASE 2 CLINICAL
TRIAL.
WE LAUNCHED A PUBLIC APPEAL, GOT
MORE THAN 74,000 SIGNATURES FROM
OUR PATIENTS, THEIR FAMILIES,
OUR BEST CLINICIANS, BEST BASIC
SCIENTISTS, AND FARA LEADERSHIP,
ALL IN DEMONSTRATING IT WASN'T
THROW THE BLOOD ON THE WALL.
IT WAS LIKE WE'RE ALL CONVINCED
THESE CLINICAL TRIAL RESULTS ARE
SUFFICIENTLY PERSUASIVE, ARE
GOING TO LEAD TO CLINICAL
BENEFIT.
THE FDA AGREED THEY WOULD
RECEIVE AND REVIEW A NEW DRUG
APPLICATION FOR THE COMPANY
BASED ON THAT APPEAL BECAUSE IT
SHOWED CONSENSUS.
THERE WAS NO DEBATE.
EVERYBODY IN OUR COMMUNITY, THE
BEST CLINICIANS THAT HAD BEEN
SEEING THESE PATIENTS FOR
DECADES, AND SO FORTH, AGREE
THIS COULD BE CLINICALLY
BENEFICIAL.
SO, THEY SAID ON THE BASIS OF
THAT APPEAL WE'LL GO AHEAD AND
RECEIVE AND REVIEW YOUR NDA.
AND REATA COMPLETED THAT ROLLING
SUBMISSION AS A RESULT OF HAVING
FAST TRACK STATUS, IN MARCH OF
LAST YEAR.
AND THEN THE LAST SUMMER THEY
SUBMITTED THE DATA THAT I'VE
ALREADY SHOWN YOU THREE
ADDITIONAL DATASETS
SUPPLEMENTING THE OTHERWISE
POSITIVE CLINICAL TRIAL RESULTS
FROM THE SINGLE CLINICAL TRIAL,
USING OUR NATURAL HISTORY
DATABASE, FOR THE FIRST TIME IN
FDA HISTORY, THEY LOOKED AT
NATURAL HISTORY DATA AS AN
EXTERNAL CONTROL TO PROVIDE
CONFIRMATORY EVIDENCE OF
OTHERWISE POSITIVE SINGLE-TRIAL
DATA.
AND THAT LED TO ON RARE DISEASE
DAY OF THIS YEAR RIGHT
DOWNSTAIRS IN THE MASUR
AUDITORIUM, JONI RUTTER OF NCATS
ABOUT TO CLOSE THE MEETING AND
SEND US HOME, HAD BEEN TEXTING
WITH ME ALL DAY, SHE NOW THAT
WAS THE DATE ON WHICH THE FDA
WAS SUPPOSED TO ANNOUNCE A
DECISION.
NOTHING YET, JONI.
I GET THE CALL AT 4:30.
JONI'S UP THERE AT THE STAGE AT
THE PODIUM LIKE THIS.
ABOUT TO CLOSE THE MEETING.
I WALKED DOWN THE AISLE,
ATTRACTED HER ATTENTION,
TOUCHDOWN SALUTE.
RON, DO YOU HAVE ANY NEWS FOR
US?
CAN YOU STEP UP TO THE
MICROPHONE AND TELL US?
I WAS ABLE TO ANNOUNCE THAT WE
GOT OUR FIRST APPROVAL.
SO FROM THE FIRST TRIAL TO THE
APPROVAL, 8 YEARS VERSUS TYPICAL
10 TO 14 YEARS, AND WE'RE JUST
REALLY THRILLED TO HAVE OUR VERY
FIRST TREATMENT.
>> I THINK I HAVE THE HARDEST
JOB TODAY BECAUSE I'M SUPPOSED
TO MANAGE TIME WHEN THERE'S GOOD
NEWS TO BE SHARED.
I'M GOING TO TINTER OVER TO OUR
COLLEAGUE FROM THE ALS
COMMUNITY, I THINK I'M STARTING
WITH NEIL.
GOOD TO SEE YOU.
I'M GOING TO ENCOURAGE YOU TO
WATCH THE CLOCK.
WE'LL TRY AND KEEP YOU TO SIX
MINTS OR -- MINUTES TO HAVE TIME
FOR TIM AND QUESTIONS.
TAKE IT AWAY.
>> I'M SORRY I COULDN'T BE HERE
TODAY.
I'M ON COVID QUARANTINE.
I WAS LOOKING FORWARD TO MEETING
YOU AND BEING ON CAMPUS.
LIKE SOME CONDITIONS WE'VE
TALKED ABOUT, ALS IS NOT AS WELL
UNDERSTOOD.
THERE'S NOT A SINGLE GENE THAT'S
IMPLICATED.
SPECIFIC CAUSES ARE UNCLEAR.
THERE'S A LOT OF HETEROGENEITY
IN THE ILLNESS, NOT EASY TO LOOK
AT UNUSED NATURAL HISTORY
CONTROLS FOR EXAMPLE TO MAKE
INFERENCES ABOUT NEW DRUGS
BECAUSE OF THE HETEROGENEITY OF
THE ILLNESS.
SO NEXT SLIDE PLEASE.
WHEN WE TALK ABOUT SUCCESS IT'S
IMPORTANT TO CONSIDER WHAT IT
TAKES TO GET TO SUCCESS AND WHAT
WE ANTICIPATE IS THE HIGH RATE
OF FAILURE OF CLINICAL TRIALS OF
DRUG CANDIDATES.
PART OF OUR STRATEGY IS TO
FOCUS, TO PLAN FOR THAT, AND TO
HAVE A DIVERSIFIED PORTFOLIO SO
WE CAN GET SUCCESSES.
AND THAT STRATEGY HAS BEEN
FAIRLY SUCCESSFUL.
AND SO THE KEY ASPECT OF HAVING
THIS STRATEGY IS TO FOCUS ON
TIME.
TIME TO POTENTIAL IMPACT.
BECAUSE WHEN YOU'RE DEALING WITH
A DISEASE WHERE THERE ARE A LOT
OF UNKNOWNS, IT'S VERY LOGICAL
AND CERTAINLY CAREFUL SCIENTISTS
WANT TO SAY LET'S FOCUS REALLY
CAREFULLY ON THE BASIC SCIENCE
OF FUNDAMENTALS, THE BIOLOGY,
GENETICS, POTENTIAL CAUSES AND
RISKS OF DISEASE, SOME WORK CAN
TAKE A VERY LONG TIME TO HAPPEN.
SO WE DO NEED TO DO THAT WORK
BUT WHILE IT'S HAPPENING IN
PARALLEL, WE NEED TO DO MORE
ADVANCED WORK, MORE CLINICAL
WORK, AT THE SAME TIME, ACCEPT
HIGHER RATE OF FAILURE IN
CLINICAL TRIALS AND CLINICAL
RESEARCH.
WE'VE BEEN DELIBERATE AND
FOCUSING ON DIVERSE CANDIDATES,
BRINGING NEW SCIENTISTS AND NEW
SCIENTIFIC TEAMS INTO THE FIELD,
AND WORKING ON OUR
INFRASTRUCTURE TO MAKE SURE WE
HAVE THE SPECIMENS, RESOURCES,
THE NETWORKS OF CLINICAL
TRIALISTS TO GET TRIALS MOVING
QUICKLY.
NOW WE HAVE DOZENS OF COMPOUNDS
UNDER STUDY IN HUMANS, WE SEE
FOLLOWING FROM NIH AND OTHER
SOURCES, $3 FOR EVERY DOLLAR WE
INVEST IN DRUG PORTFOLIO, IT'S
$6 OF FOLLOW-ON FUNDING, HUGE
INCREASE IN FEDERAL ALS RESEARCH
FUNDING IN PART BECAUSE OF
WHAT'S GOING ON AT NINDS AND
DEMENTIA DISCOVERY FUNDS, BUT
ALSO THROUGH ADVOCACY WORK
THROUGH DEPARTMENT OF DEFENSE
MORE THAN 300% INCREASE THROUGH
2013, THE ICE BUCKET CHALLENGES
MADE A HUGE IMPACT, MORE MONEY
THROUGH PHILANTHROPIC SPACE,
MORE FUNDING IN THE FEDERAL
SPACE.
NEXT PAGE.
THE NEXT PART IS HOW WE WORK
WITH THE FDA.
WE'VE GONE THROUGH THE FDA
PROCESS, WE'VE HAD THE
PATIENT-FOCUSED DRUG DEVELOPMENT
MEETINGS WITH THE FDA.
WE WORKED ON A TRIAL GUIDANCE
THAT WAS ADOPTED, BECAME
OFFICIAL, IN 2019.
I THINK WHAT'S EVEN MORE
IMPORTANT IS WHEN A DRUG DOES GO
TO FDA FOR APPROVAL ON OCCASION
THE ASSOCIATION DOES TAKE A
STAND IN THAT PROCESS.
WE MAKE STATEMENTS, SOME CASES
ENGAGE IN ADVOCACY OUTSIDE OF
THIS PDUFA PROCESS, TRIAL
GUIDANCE.
AND WE HAVE TO BE CAREFUL ABOUT
OUR CONFLICTS OF INTEREST.
WE HAVE PHARMA PARTNERS WHO
SPONSOR ACTIVITIES, WE FUNDED
SOME DRUGS UNDER REVIEW BY THE
FDA.
SOMETIMES IT'S BOTH.
ON TOP OF THAT, WE ALL AS STAFF
KNOW PEOPLE WHO ARE
PARTICIPATING IN THESE PHASE 3
TRIALS.
WE RESPECT THEM.
THEY SHAPE OUR OPINIONS.
THAT'S WHY WE WORK REALLY HARD
TO MAKE SURE WE HAVE AN
INDEPENDENT OUTSIDE REVIEW OF
DRUG DATA BEFORE WE MAKE
STATEMENTS ON WHETHER WE THINK
THE FDA SHOULD APPROVE SOMETHING
OR NOT.
WE CAN ONLY DO THAT IF THE
COMPANY IS WILLING TO LET US
HAVE ACCESS TO THAT DATA BECAUSE
SOME IS PRY PRY TEAR --
PROPRIETARY.
WE WOULD LIKE THE FDA TO VIEW
DRUG APPROVALS IN THE ALS SPACE
WITHIN THE CONTEXT OF ALS.
RARE DISEASE WITH NO CURE THAT'S
RAPIDLY PROGRESSIVE SO THAT'S A
DIFFERENT STANDARD THAT ONE
WOULD EXPECT FOR A DISEASE THAT
HAS A CURE.
STAND AROUND FOR HEARTBURN
MEDICATION, ALS MEDICATION, THEY
SHOULD BE DIFFERENT.
NEXT SLIDE, WE HAD AN
INTERESTING STUDY FOR APPROVAL
OF A DRUG, AMX 0035, APPROVED
UNDER THE NAME RELIVRIO.
THE ADVISORY COMMITTEE IN MARCH
OF 2022 WAS ASKED TO ESTABLISH
CONCLUSION IT IS EFFECTIVE IN
TREATMENT OF PATIENTS WITH ALS,
TOOK A VOTE, THOUGHT THERE
WASN'T ENOUGH EVIDENCE TO
ESTABLISH CONCLUSION.
SO WE PUSHED BACK, THE COMMUNITY
PUSHED BACK, THERE WAS
PETITIONS, AND THEY HELD A
SECOND ADVISORY COMMITTEE AND
ASKED THE SAME DRUG, ASKED A
DIFFERENT QUESTION.
THAT IS, IS THE AVAILABLE
EVIDENCE OF EFFECTIVENESS
SUFFICIENT TO SUPPORT APPROVAL?
DIFFERENT STANDARD.
YOU MAY TAKE INTO ACCOUNT UNMET
NEED AND STATUS OF TRIAL AND SO
ON AND SERIOUSNESS.
A PUBLIC HEALTH APPROACH, ASKING
PEOPLE TO CONSIDER CONTEXT OF
DRUG, DISEASE, WHEN MAKING
DECISION.
THAT ADVISORY COMMITTEE DID VOTE
FOR APPROVAL.
SO IF YOU GO TO THE NEXT SLIDE
PLEASE.
SO, WHAT'S THE SUCCESS OF THIS?
WE'VE GONE FOR A LONG TIME WITH
SLOW CHANGES IN THE TREATMENT
LANDSCAPE, AND GRADUAL INCREASE
IN ACCELERATION, IN APPROVAL OF
TREATMENTS, IN THE PAST YEAR TWO
TREATMENTS APPROVED, VERY
UNUSUAL IN THE ALS SPACE BECAUSE
APPROVAL PRIOR TO THAT WAS IN
2017.
ARE WE READY FOR THIS CHANGE IN
ALS TREATMENT?
WE'RE TALKING ABOUT NOW MULTIPLE
TREATMENTS THAT ALL HAVE MODEST
EFFECTS, SO PERHAPS THEY CAN
WORK IN COMBINATION, PERHAPS
THEY CAN'T.
WE'RE HAVING CHALLENGES SINCE
THEY ARE EXPENSIVE MAKING SURE
EVERYONE WHO CAN BENEFIT CAN GET
THESE TREATMENTS.
WE HAVE TROUBLE GETTING PEOPLE
DIAGNOSED AND REFERRED TO
SPECIALTY CENTERS.
AND THEN PEOPLE STILL HAVE
COMPLICATIONS FROM ALS CAUSING
SIGNIFICANT HARM, FALLS, ET
CETERA.
INSURANCE COMPANIES, WE DON'T
NECESSARILY HAVE CLINICAL BASE
FOR HOW MUCH THINGS COST TO MAKE
SURE WE KNOW HOW TO DELIVER CARE
EFFECTIVELY.
SO THIS IS A CHALLENGE.
AND CANCER HAS BEEN DEALING WITH
ISSUES OF HOW TO GET PEOPLE
DIAGNOSED AND GET PEOPLE IN
TREATMENT, SO ACTUAL SURVIVAL
CAN IMPROVE FOR A LONG TIME.
WHEN I TALKED ABOUT THIS WITH MY
RESEARCH COLLEAGUES I DON'T GET
THE SAME EXCITEMENT OR ATTENTION
TO FIGURING OUT HOW TO IMPROVE
CARE.
PART MIGHT BE THE WAY WE'RE
ALLOCATING FUNDING.
NCI SPENDS 25% ON TREATING
CANCER AND IMPROVING
SURVIVORSHIP.
THE EXTRAMURAL BUDGET AT NINDS
IS ONLY 4% FOR CLINICAL
RESEARCH, WHICH ISN'T EVEN QUITE
THE SAME THING.
I THINK WE HAVE SOME WORK TO DO
BOTH ON THE FEDERAL SIDE AND
CERTAINLY AT THE ASSOCIATION
SIDE, INCLUDING OUR CAPACITY TO
STUDY QUALITY OF CARE,
INCREASING NUMBER OF SCIENTISTS
TRAINED TO DO THIS KIND OF WORK,
WE LAUNCHED A QUALITY OF CARE
RFA AT THE ASSOCIATION THIS YEAR
AND THIS IS THE FIRST TIME WE'VE
DONE THAT.
I THINK THE WHOLE FIELD HAS TO
ACCOMMODATE TO THE IDEA THAT NEW
TREATMENTS ARE HERE AND HAVE TO
FIGURE OUT HOW TO MAKE THEM
WORK.
I BELIEVE THAT'S MY LAST SLIDE.
THANK YOU.
>> IT'S INTERESTING WHEN YOU
THINK ABOUT THE ACHIEVEMENT,
HAVING THERAPIES BUT THEN HOW DO
YOU HELP PATIENTS AND FAMILIES
NAVIGATE THAT LANDSCAPE, WHAT
DOES ACCESS LOOK LIKE, A LOT TO
BE CONSIDERED.
THERE ARE QUESTIONS COMING IN SO
WHAT STANDS BETWEEN US AND
QUESTIONS IS DR. TIM MILLER.
WE'RE GOING TO SHOW TIM'S
PRESENTATION AND OPEN FOR SOME
CONVERSATION.
>> I'M TIM MILLER, A NEUROLOGY
AT WASHINGTON UNIVERSITY IN
ST. LOUIS.
I'M DELIGHTED TO PARTICIPATE IN
THIS NON-PROFIT FORUM.
I'LL START WITH INDUSTRY
COLLABORATIONS, IONIS
PHARMACEUTICALS, AND BIOGEN,
RUNNING CLINICAL STUDIES.
SUCCESS STORIES IN ALS,
HIGHLIGHTING TWO IN FIVE TO FIX
MINUTES, THERAPY HAS BEEN SLOW
AND IMPROVES, AND DEMONSTRATION
OF USEFUL BLOOD BIOMARKER.
TWO OTHERS, FASTER WAY TO TEST
NEW THERAPIES AND EDUCATE THE
COMMUNITY.
90% IS SPORADIC, 10% IS
FAMILIAL.
MUTATIONS IN GENE SUPEROXIDE
DISMUTASE 1 ACCOUNTS FOR 10 TO
20%, THAT'S 300 TO 350 PEOPLE IN
THE UNITED STATES.
THE RATIONALE FOR LOWERING SOD1
IS MUTANT SOD1 ACQUIRES NEW
TOXICS PROPERTY, DECREASING IS
LIKELY TO BE BENEFICIAL,
DECREASING IS LIKELY TO BE SAFE
MUTATIONS IN THE GENES CAUSE
ABNORMAL RNA, THAT LEADS TO THE
TOXIC PROTEIN, ANTISENSE DRUGS
CAN BLOCK DISEASE CAUSING RNA
AND TOXIC PROTEIN.
TALKING ABOUT THE VALOR TRIAL,
PHASE 3 USING TOFERSEN,
ANTISENSE OLIGONUCLEOTIDE, 72
PARTICIPANTS ON DRUGS, 36 ON
PLACEBO, THREE DOSES IN THE
FIRST MONTH, A DOSE ABOUT ONCE A
MONTH AFTER THAT.
IT DOES NOT CROSS THE
BLOOD-BRAIN BARRIER, DELIVERED
TO THE BRAIN AND SPINAL CORD
INTRATHECAL SO THE AREA BELOW
THE SPINAL CORD, INTRODUCING THE
DRUG, THEN THROUGHOUT THE BRAIN
AND SPINAL CORD.
WHEN INTRODUCING, THE GROUP IN
BLUE ARE ON PLACEBO UNTIL HERE
AT 28 DAYS, OPEN LABEL EXTENSION
THEY RECEIVE DRUG.
GROUP IN RED ON THE DRUG FROM
THE BEGINNING.
BOTH GROUPS YOU SEE LOWERING IN
THE CEREBROSPINAL FLUID, EXACTLY
WHAT THE DRUG IS SUPPOSED TO DO.
TO READ OUT WHETHER IT HAD
EFFECT WE LOOKED AT NEURO
FILAMENTS, PROTEINS THAT ARE IN
THE AXON, CONNECTION BETWEEN THE
MOTOR NEURON AND OUT HERE, THE
MUSCLE.
CONNECTING IN BETWEEN THE AXON
WHEN THOSE AXONS ARE INJURED AS
OCCURS IN ALS, OTHER DISORDERS,
THEY LEAK OUT WHERE WE CAN
MEASURE THEM.
THEY PREDICT SURVIVAL, AT FOUR
YEARS WITH LOW NEUROFILAMENT
MORE THAN 60% SURVIVING.
NEUROFILAMENTS WERE LOWERED IN
THIS GROUP HERE, AND THEN ON
DRUG NEUROFILAMENTS COME DOWN.
MY INTERPRETATION IS SUBSTANTIAL
SLOWING OF THE DISEASE PROCESS.
THIS DID NOT MEET A PRIMARY
ENDPOINT, ALS FUNCTIONAL RATINGS
SCALE NOT MUCH DIFFERENT AT 28
WEEKS.
OPEN LABEL EXTENSION, 52 WEEKS,
,
YOU SEE A DIFFERENCE BETWEEN
DRUGS AND PLACEBO.
THIS IS MY FAVORITE PIECE OF
DATA FROM THIS STUDY.
THIS IS A HAND-HELD DYNAMOMETRY,
INCREASE IN STRENGTH, 27% OF THE
PEOPLE INITIALLY ON THE DRUG HAD
INCREASE IN STRENGTH.
I ASKED THE GROUP HERE, 178
YEARS OF TAKING CARE OF
PATIENTS, THE ANSWER IS ZERO.
WE HAVEN'T SEEN SOMEONE IN OUR
CENTER GETTING BETTER.
IN THIS STUDY 27% INCREASED
STRENGTH.
REMARKABLE STORIES, ONE STORY
FROM THE FDA ADVISORY COMMITTEE,
I'M DOING THINGS I COULD NOT DO,
LIMP HAS GONE FROM OBVIOUS TO
BARELY PER SUSCEPTIBLE, I CAN GO
TO MY OFFICE AGAIN, SHOWER
WITHOUT MY SHOWER CHAIR.
CONCLUSIONS LOWERING SOD1 LOWERS
NEURO FILAMENT, SUBSTANTIAL
SLOWING OF THE NEURODEGENERATIVE
DISEASE PROSET.
STABILIZATION OF FUNCTION,
BREATHING, STRENGTH, SOME
EVIDENCE OF IMPROVING,
REMARKABLE INDIVIDUAL STORIES.
OVERALL WELL TOLERATED, THERE
WERE NOTEWORTHY SIDE EFFECTS.
I'LL BE HAPPY TO DISCUSS.
THIS WAS APPROVED BY FDA APRIL
THIS YEAR.
ALS IS A TREATABLE DISORDER, THE
MOST PRO FOUND CONCLUSION, YOU
NEED THE RIGHT DRUG,
NEUROFILAMENT IS ESTABLISHED AS
A THERAPY-RESPONSE IMBIOMARKER.
IN MY OPINION PREDICTIVE OF
SUCCESS OR FAILURE, EFFECTIVE
DRUG MAY NOT CHANGE
NEUROFILAMENT.
I WANT TO GIVE A SHOUT OUT TO
THE STUDY PARTICIPANTS, WITHOUT
THEM THIS STUDY OF COURSE WOULD
NOT GO.
ALSO TO PRINCIPAL INVESTIGATORS
AND HARD-WORKING SITE STAFF,
STEERING COMMITTEE AND MY
COLLEAGUES AT BIOGEN.
THANK YOU AND I LOOK FORWARD TO
QUESTIONS.
[APPLAUSE]
HE MAY BE JOINING US.
AH, THERE HE IS.
>> I'M HERE.
GREAT TO BE HERE.
REALLY ENJOYED THE DAY.
>> THANK YOU SO MUCH.
WE'RE RUNNING BEHIND BUT WE'LL
TAKE THE EXTRA TEN MINUTES FOR
QUESTIONS.
I HAVE QUESTIONS THAT WE THOUGHT
ABOUT BUT KNOWING THAT WE ONLY
HAVE TEN MINUTES LEFT I WANT TO
START WITH QUESTIONS FROM THE
AUDIENCE IF ANYONE HAS ANY
QUESTIONS.
THOUGHTS, OBSERVATIONS?
I SEE ONE IN THE BACK.
REBECCA IS GETTING A WORKOUT
RUNNING UP AND DOWN THE STAIRS.
>> I'M KIM WITH THE CHRISTOPHER
AND DANA REID FOUNDATION.
I WANT TO COMMEND YOU FOR YOUR
EXTRAORDINARY WORK AND I WAS
CURIOUS ABOUT HOW DO YOU MAN
EXPECTATIONS, THE APPROVAL
PROCESS, REIMBURSEMENT PROCESS,
ACCESS.
I DON'T WANT TO DEFLATE THESE
EXTRAORDINARY ACCOMPLISHMENTS
BUT THIS IS A CONCERN A LOT OF
ORGANIZATIONS HAVE AND WE'RE
TALKING ABOUT THAT INTERNALLY AT
THE FOUNDATION TOO.
WHEN WE SEE THESE HUGE
SUCCESSES, AND THE COMMUNITY IS
DESPERATE TO GET THEM.
>> GREAT QUESTION.
THANK YOU SO MUCH.
I'M GOING TO PASS IT TO MELISSA.
>> I'M VERY GRATEFUL FOR THE
QUESTION.
I DIDN'T SHARE I WAS A 30-YEAR
HOSPITAL AND HEALTH CARE
ADMINISTRATOR, LIVED THE PAIN OF
PAYMENT ISSUES, NOT BEING ABLE
TO DO THE RIGHT THING FOR
PATIENTS BECAUSE OF HOW HEALTH
CARE IS PAID FOR IN OUR COUNTRY.
SO I APPRECIATE THAT.
FROM THE VERY BEGINNING OF MY
TIME WITH THE FOUNDATION I WAS
INTERESTED IN THE SCIENCE AND
INTERESTED IN HOW IT WAS
PROGRESSING, THE COMPOUND WAS
PROGRESSES, MOST INTERESTED IN
US PREPARING FOR POST-APPROVAL.
AND AFFORDABILITY AND ACCESS.
I WILL SHARE A LITTLE BIT ABOUT
WHAT WE'RE DOING.
WE ARE ABOUT 65% OF THE FAMILIES
WHO HAVE RETT SYNDROME RECEIVE
THEIR INSURANCE THROUGH PUBLIC
PAYERS, AND JUST ONE EXAMPLE,
I'M SURE THERE ARE OTHERS, WE'VE
MOVED STRONGLY INTO AN ADVOCACY
WORLD, TEACHING FAMILIES HOW TO
ADVOCATE FOR COVERAGE NOT
SPECIFIC TO ONE COMPOUND BUT
COVERAGE IN GENERAL AT THE STATE
LEVEL.
WE'VE ENGAGED WITHED ADVOCACY
FIRMS TO TEACH FAMILIES TO GO TO
MEETINGS AT STATE LEVELS,
PREPARE FOR THOSE CONVERSATIONS,
ADVOCATE.
WE HAD A HUGE SUCCESS LAST IF I
WITH A MOM GOING TO THE MEETING
IN TEXAS GETTING TEXAS MEDICAID
TO COVER DAYBUE, YEAH.
>> IN TERMS OF PREPARING
EXPECTATIONS, WE WERE VERY
ADAMANT ABOUT THAT DURING THE 8
YEARS OF DEVELOPMENT OF THIS
DRUG.
WE SAW FROM THE BEGINNING IT
WOULD NOT BE CURATIVE, WOULD NOT
BE EVEN PROFOUNDLY BENEFICIAL.
WE PREPARED OUR PATIENT FAMILIES
FOR THE IDEA THAT THIS WOULD
SLOW THE PROGRESSION, IF IT
WORKED IT WOULD SLOW
PROGRESSION, GIVE THEIR PATIENTS
A LITTLE MORE TIME.
HIGHER QUALITY OF LIFE OVER THAT
PERIOD OF TIME, WHILE THE MORE
MAYBE GENE-BASED THERAPIES HAD
THAT MUCH MORE TIME TO DEVELOP.
IN TERMS OF THE COVERAGE, WE
WORKED CLOSELY WITH THE COMPANY
AND THEY HAVE WORKED AT A
PROGRAM BOTH PATIENT ASSISTANCE
TO ASSURE THAT EVERY ELIGIBLE
PATIENT CAN GAIN ACCESS.
IF THEY CAN'T AFFORD, YOU KNOW,
HAVE NO INSURANCE OR ARE
UNDERINSURED.
ON THE OTHER HAND, IT'S
IMPOSSIBLE TO GO TO ALL THE
PAYERS AND CONVINCE THEM TO
COVER.
THAT'S JUST A DAY-TO-DAY TRIAL
TRYING TO CONVINCE PAYERS AND WE
DIDN'T HAVE A METHOD OF GOING TO
ALL PAYERS IN ADVANCE TO PREP
THEM.
SO IT'S A TOUGH ONE.
YOU RAISED A VERY GOOD QUESTION
>> I AM GOING TO TURN IT OVER TO
NEIL.
AND I WANT TO MAKE SURE KIM CAN
TALK.
>> I THINK IT'S A REALLY
IMPORTANT QUESTION.
AND THE ASSOCIATION WE'VE RAMPED
UP WITH CMS CONSIDERABLY, THEY
DON'T HAVE THE PATIENT FOCUS OR
PROCEDURES IN PLACE TO INCLUDE
PATIENTS THE WAY THE FDA DOES.
SO IT'S BEEN MORE OF A
CHALLENGE.
AT THE SAME TIME A LOT OF
INSURANCE DECISIONS ARE MADE ON
THE STATE LEVEL.
SO WE'VE BEEN INVOLVED HEAVILY
ON DIFFERENT INSURANCE ISSUES TO
COVER MEDI GAP COVERAGE AND
OTHER VERY COMPLEX FINANCIAL AND
PAYMENT ISSUES.
THE UNDERLYING FUNDAMENTALS
WHETHER A DRUG WORKS OR NOT AND
HOW TO DELIVER A DRUG TO
SOMEONE, FIRST YOU HAVE TO
DIAGNOSE THEM, FIND THEM.
YOU CAN'T RUN A SUCCESSFUL
CLINICAL TRIAL ENTERPRISE OR
TREAT PEOPLE UNLESS YOU GET THEM
DIAGNOSED.
ALL OF THOSE QUESTIONS HAVE
SCIENTIFIC COMPONENTS THAT
HAVEN'T BEEN FULLY EXPLORED AND
NEED MORE WORK, AND WE'RE TRYING
TO BUILD CAPACITY ON THE
RESEARCH SIDE TO STUDY THESE
QUESTIONS AS WELL AS DEAL WITH
THEM AS ADVOCACY ISSUES.
THEY NEED BOTH LIKE DRUG
APPROVAL NEEDS ADVOCACY AND
SCIENTIFIC COMPONENT.
>> I CAN JUMP IN BRIEFLY.
MOST OF IT'S BEEN COVERED.
WE'LL SEE IT'S JUST BEGINNING TO
GET OUT, DIAGNOSED WITH A
GENETIC FORM IS A KEY PART,
GENETIC TESTING WILL BE MORE
WIDELY USED IN ALS CLINICS, NOW
A TREATABLE FORM OF THE DISEASE
RELATED TO GENETIC FINDINGS.
AND THEN WE'LL ROLL OUT AND I
THINK PUSH THIS OUT AND
HOPEFULLY AS MANY PEOPLE AS
NEEDED WILL GET ON IT QUICKLY.
DELAY IS NOT GOOD.
WE SAW SIX MONTHS OF DELAY IN
OUR STUDY.
HIGHLIGHTED SUCCESS OF PEOPLE
EARLY ON, AND SIX MONTHS DELAYS
ALSO DID BETTER THAN OTHERWISE,
THAT'S MY INTERPRETATION OF
THOSE DATA.
BUT THEY DIDN'T DO AS WELL.
TIME REALLY DOES MATTER,
EVERYONE IN THIS AUDIENCE
ALREADY KNOWS THIS.
GETTING PEOPLE ON A DRUG LIKE
TOFERCIF AND AS IT'S BEEN
RENAMED AS SOON AS POSSIBLE WILL
BE KEY TO PRESERVING FUNCTION.
>> TIME IS NOT ON OUR SIDE.
I CAN SPEAK IN THE HD SPACE
WE'RE WAY TOO FAMILIAR WITH
FAILURE.
SO MANAGING EXPECTATIONS IS
HEARTBREAKING.
WE DO HAVE A QUESTION ONLINE.
>> THIS IS A QUESTION FROM JEAN
SWIDLER FOR DR. MILER.
DO YOU EXPECT A BETTER RESPONSE
TO ALS THERAPIES AFTER SYMPTOMS
OR BEFORE SYMPTOM ONSET IN
GENETIC ALS?
>> HI, JEAN.
ALWAYS GOOD TO HEAR FROM YOU.
WE'VE DISCUSSED THIS BEFORE.
IT'S A VERY GOOD POINT.
TREATING SOMEBODY AT THE
EARLIEST POINT POSSIBLE MIGHT
MEAN TREATING THEM EVEN AT A
BIOMARKERS CHANGE OR PERHAPS
BEFORE, THAT AT THE EARLIEST
INDICATION THAT THE DISEASE IS
COMING.
AS SOON AS WE KNOW THAT WITH
CLARITY, THE DISEASE IS COMING,
TO GET SOMEBODY ON A DRUG AS
QUICKLY AS POSSIBLE, TESTED IN
THE SETTING OF ATLAS TRIAL
LOOKING FOR BIOMARKERS CHANGE,
GETTING THEM ON THE DRUG AS SOON
AS POSSIBLE BEFORE THEY HAVE
MOTOR MANIFESTATIONS OF ALS, A
TRIAL FROM BIOGEN AND MICHAEL
BENATAR.
AS SOON AS POSSIBLE I THINK IS
BETTER.
WE MIGHT BE ABLE TO PREVENT ALS
ALTOGETHER IF WE CAN GET PEOPLE
ON A DRUG VERY EARLY.
AGAIN, THAT'S BEING TESTED.
AND I WOULD PREDICT THAT THAT'S
LIKELY TO BE TRUE, THOUGH
GENERAL IT'S BEING TESTED IN A
CLINICAL, AND EARLY IS GOING TO
BE BETTER, I THINK, ALWAYS THAN
LATER.
ONE LAST QUESTION, PENNY?
>> I'LL MAKE IT SHORT.
ALL NEUROLOGICAL DISEASE HAS A
HORRIBLE SUCCESS RATE IN DRUG
DEVELOPMENT, I WANT TO TAKE A
MOMENT TO CELEBRATE THERE'S FOUR
NEW DRUGS FOR RARE NEUROLOGICAL
DISEASES.
>> LIKE I SAID, I'M JEALOUS.
WE NEED TO GET BACK ON SCHEDULE,
I'LL TURN IT OVER TO DR.
KOROSHETZ.
I WANT TO THANK THE SPEAKERS.
NEIL, HOPE YOU FEEL BERT. --
BETTER.
THANK YOU ALL FOR BEING PART OF
THIS.
>> THANK YOU VERY MUCH.
>> THAT WAS A FANTASTIC SESSION,
I MUST SAY.
ACTUALLY HAVE THREE DRUGS IN A
YEAR, A RECORD FOR NINDS.
IT'S A TESTIMONY TO THE HARD
WORK OF ALL THE PEOPLE WHO MADE
THIS HAPPEN.
HERE AT NINDS WE LOOK AT THE BIG
PICTURE.
AND I'M HOPING THAT AS NEIL SAID
THERE IS GOING TO BE MORE AND
MORE THERAPIES COMING OUT, MORE
SUCCESSFUL, EVERY YEAR.
JUST TO SET THE STAGE, HASN'T
ALWAYS BEEN THIS GOOD.
SO WE, AS PENNY SAID, A LOT OF
TRIALS DIDN'T WORK AT ALL.
USUALLY THE REASON IS BECAUSE WE
MADE THESE ASSUMPTION ABOUT THE
DRUG OR ABOUT THE DISEASE, AND
WE WERE WRONG, THOSE
ASSUMPTIONS, AND THEY CAME BACK
TO BITE US.
AT NINDS WHAT WE TRY TO DO IS
KIND OF LIKE YOU INVEST IN YOUR
PORTFOLIO, YOUR FINANCIAL
PORTFOLIO, IN TERMS OF ACROSS
THE SPECTRUM OF ACTIVITIES, AND
ALWAYS TRYING TO KEEP OUR EYE ON
THE BALL IN TERMS OF THE HEALTH
OF THE DIFFERENT PARTS OF THE
PUZZLE.
WE ALSO WATCH WHAT YOU DO, WE
TRY AND BE COMPLEMENTARY, LOOK
AT WHAT THE INDUSTRY DOES, TRY
AND MAKE THEIR CHANCE OF SUCCESS
GREATER AS THEY GO INTO THESE
THINGS AND TRY TO PULL INDUSTRY
IN.
I'M GOING TO TALK ABOUT THE
INSTITUTE IN GENERAL.
SO, TO THE POINT I JUST MADE, IN
TERMS OF INVESTING ACROSS THE
SPECTRUM, WE HAVE THESE THREE
DIVISIONS OF SCIENCE, DIVISION
OF NEUROSCIENCE, DIVISION OF
TRANSLATIONAL RESEARCH, I DON'T
SEE AMIR HERE, AND PEOPLE FROM
DTR, AND DIVISION OF CLINICAL
RESEARCH.
AND WE INVEST HEAVILY ON THE
BASIC SIDE TO UNDERSTAND
MECHANISM OF DISEASE.
IN FACT, PROBABLY ABOUT 65% OF
OUR MONEY GOES TO THIS BASIC
RESEARCH.
ABOUT 22% OF OUR MONEY GOES TO
UNDERSTANDING HOW THE BRAIN
WORKS IN GENERAL.
THAT'S DISEASE AGNOSTIC.
ABOUT 50% GOES TO BASIC
MECHANISMS OF DIFFERENT
DISEASES.
AND WE HAVE HUNDREDS OF DISEASES
IN OUR PORTFOLIO, SO THERE'S NO
DISEASE THAT GETS ENOUGH MONEY.
IT'S SPREAD OUT DEPENDING HOW
YOU COUNT NOW, MEASURE UP TO 400
DIFFERENT NEUROLOGIC DISEASES.
AND DIVISION OF CLINICAL
RESEARCH DOES CLINICAL TRIALS.
BUT IN BETWEEN WE HAVE THIS
GROUP CALLED DIVISION OF
TRANSLATIONAL RESEARCH, THE
PURPOSE OF THAT GROUP IS TO
FACILITATE DEVELOPMENT OF NEW
THERAPIES.
AND WE ARE NOT A DRUG COMPANY.
BUT WE RELY ON DRUG COMPANIES TO
TAKE ADVANCING OUT OF THE
RESEARCH WE FUND IN THESE BASIC
MECHANISMS OF DISEASE TO BRING
PRODUCTS TO PEOPLE.
SO NOW IN OUR BUSINESS THERE ARE
SOME DISEASES THAT HAVE A LOT OF
INDUSTRY INTEREST.
IT TENDS TO WAX AND WANE.
WE HAVE A LOT OF DISEASES THAT
HAVE NO INDUSTRY INTEREST.
AND THERE WHAT WE TRY TO DO IS
DEVELOP THINGS SO THAT IT LOOKS
LESS RISKY.
USUALLY THE COMPANIES DON'T --
IT'S NOT THAT THEY DON'T FEEL
THEY CAN MAKE MONEY.
THE PROBLEM IS THAT THE RISK OF
FAILURE IS SO HIGH, THAT'S
BECAUSE OF INHERENT PROBLEM
DEVELOPING DRUGS FOR NERVOUS
SYSTEM DISEASES.
THERE'S A HIGH FAILURE RATE,
ASPENY MENTIONED, WE THINK
THAT'S RELATED TO OUR LACK OF
KNOWLEDGE.
CANCER TRIES TO KILL CELLS,
WE'RE TRYING TO KEEP CELLS
ALIVE.
IT'S NOT IMPOSSIBLE.
TAKES A LOT OF HARD WORK, A
LITTLE LUCK.
FROM RON'S SAGA DECADES TO GET
THERE BUT IT'S ALL WORTH IT
BECAUSE OF THE IMPORTANT IMPACT
THESE THERAPIES HAVE.
DIVISION OF TRANSLATIONAL
RESEARCH IS PEOPLE WHO CAME IN
FROM PHARMACEUTICAL COMPANIES,
WHEN MOST COMPANIES DROPPED
NEUROSCIENCE PROGRAMS BECAUSE
THEY FELT THEY WERE TOO RISKY.
SO THAT'S KIND OF OUR GENERAL
OVERALL LOOK AT THINGS.
IF YOU LOOK AT WHAT INDUSTRY
DOES, IT'S A PYRAMID, EXACTLY
THE OPPOSITE OF OURS.
MOST OF THEIR MONEY WILL GO INTO
THESE BIG EXPENSIVE CLINICAL
TRIALS.
GETTING THINGS TO FDA APPROVAL.
MOST OF OUR MONEY IS
UNDERPINNING THAT, AND WITHOUT
US THERE WOULDN'T BE THE DISEASE
RESEARCH THAT'S NEEDED FOR THE
INDUSTRY TO MOVE FORWARD.
IT'S VERY COMPLEMENTARY TO WHAT
THE INDUSTRY DOES.
WE WORK WITH THEM CLOSELY.
WE HAVE A NUMBER OF
PUBLIC/PRIVATE PARTNERSHIPS,
ALWAYS INTERESTED IN DISCUSSING
THINGS WITH INDUSTRY.
WE HAVE A COUPLE PROGRAMS REALLY
FOCUSED ON INDUSTRY TO MOVE
THINGS FORWARD, MOSTLY SMALL
BIOTECHS, SMALL BUSINESS GRANTS.
OOPS, WRONG WAY.
AND WE ALSO HAVE THE INTRAMURAL
PROGRAM, YOU HEARD FROM REGHAN
FOLEY TODAY, THAT'S ANOTHER
SPECIAL PLACE BECAUSE THERE'S A
RESEARCH HOSPITAL.
IF YOU TRY AND DO RESEARCH OUT
IN THE EXTRAMURAL SPACE,
INCREDIBLY EXPENSIVE, AND
CERTAINLY VERY HARD TO DO
ANYTHING THAT REQUIRES SOMEBODY
ACTUALLY STAYING IN THE HOSPITAL
OVERNIGHT.
MOST OF THE TRIALS YOU HEARD
ABOUT ARE BASICALLY OUTPATIENT
TRIALS, BUT THERE'S SOME THINGS
WHERE YOU NEED TO BRING PEOPLE
IN, KEEP THEM IN FOR WEEKS,
SOMETIMES AT A TIME.
CERTAINLY THE GENE THERAPY
SPACE, THAT'S LIKELY TO BE THE
CASE, CERTAINLY IN THE
BEGINNING.
SO THE HOSPITAL HERE CAN
ACTUALLY DO THAT.
IT'S NOT FUNDED ON GRANTS.
THE PEOPLE IN THE INTRAMURAL
PROGRAM ARE FEDERAL EMPLOYEES.
AND THEY HAVE A SALARY AND THEY
HAVE A BUDGET THAT THEY CAN
COUNT ON MOSTLY FROM YEAR TO
YEAR, DEPENDING WHAT CONGRESS
DOES.
IT'S A VERY DIFFERENT ATMOSPHERE
THAN ON THE OUTSIDE WHERE
THERE'S A WHOLE BUNCH OF
COMPETING INTERESTS.
SO OUR PROGRAM, ON THE
INTRAMURAL SIDE, HAS HIGH
QUALITY BUT IT'S FOCUSED IN
PARTICULAR AREAS, NOT LIKE A
GENERAL HOSPITAL WHERE THEY HAVE
PROGRAMS IN ALL DISEASES, THEY
HAVE I WOULD SAY COMPARED TO
WHERE I CAME FROM MIGHT COVER
15% OF DISEASES THAT A GENERAL
HOSPITAL WILL COVER BUT THEY CAN
DO THINGS YOU CAN'T DO IN A
GENERAL HOSPITAL.
HOW DO WE MAKE FUNDING
DECISIONS?
NEIL MENTIONED CANCER INSTITUTE,
WHICH DOES A LOT OF TOP-DOWN
FUNDING.
AND WE TEND TO BE THE OPPOSITE,
A LOT OF BOTTOM-UP.
I'M NOT SAYING WE'RE BETTER.
WE HAVE TO THINK ABOUT WHERE WE
ARE AND HOW WE DO THIS.
YOU CAN SEE THIS DARK BLUE AREA
CALLED INVESTIGATOR INITIATED
RESEARCH, SO WHAT THIS MEANS IS
THESE ARE RESEARCH OPPORTUNITIES
THAT ARE OPEN FOR ANYBODY TO
COME IN, AND SUBMIT GRANTS, GET
REVIEWED, GET A SCORE, PAY THE
GOOD SCORES UNTIL WE RUN OUT OF
MONEY, AND THAT'S HOW, AS YOU
CAN SEE HERE, THAT'S 60, 70% OF
OUR MONEY.
IT'S REALLY NOT TOP-DOWN.
WHEN YOU HAVE 400 DISEASES,
PLAYING FAVORITES IS VERY TRICKY
FOR ME ANYWAY.
I HATE MY DISEASES AND LOVE THEM
ALL EQUALLY.
WHAT THIS DOES, BASICALLY IS
COMPETITION.
SO, THAT ACCOUNTS FOR A LOT OF
DISPARITIES.
WE HAVE SOME RESEARCH WHERE A
LOT OF PEOPLE COME IN.
THERE'S A LOT OF PROGRESS THEY
THINK THEY CAN MAKE, THEY ARE
GOING TO GET GRANTS, THAT MONEY
RISES IN THAT AREA OF RESEARCH.
THERE ARE ALSO AREAS STRUGGLING
TO PULL PEOPLE IN BECAUSE THEY
DON'T HAVE THE TOOLS, PEOPLE
CAN'T FIGURE OUT EXACTLY HOW TO
GET AT THIS CONDITION, AND SO,
YEAH, THOSE CONDITIONS SUFFER.
AND WE LOOK FOR THOSE AND
SOMETIMES WILL PUT OUT A
PARTICULAR CALL FOR GRANTS IN
THIS SPACE.
I MUST SAY THAT DOESN'T WORK
VERY WELL.
PEOPLE THINK THAT BY PUTTING
MONEY ON THE STREET THAT'S GOING
TO MAKE IT HAPPEN.
THAT'S NOT TRUE.
PEOPLE WILL RESEARCH WHAT THEY
ARE PASSIONATE ABOUT
RESEARCHING.
IF THEY ARE NOT PASSIONATE, THEY
WILL SEE WHAT THEY ARE
PASSIONATE ABOUT.
WHAT WE RELY ON IS PEOPLE IN THE
ROOM AND ON ZOOM TO REALLY HOOK
PEOPLE ON NEURODISEASE, MAKE
THEM PASSIONATE RESEARCHERS,
CLINICAL TRIALISTS, BASIC
SCIENTISTS TO PUSH HARD IN THAT
DISEASE.
GOVERNMENT PUTTING OUT MONEY
DOESN'T REALLY DO THE TRICK IN
TERMS OF GETTING REALLY GOOD
PEOPLE TO COME INTO AN AREA.
NOW, WE DO CERTAIN THINGS WHERE
WE TRY AND PULL A LIKE AREA IN
TO ANOTHER AREA THAT'S NOT DOING
AS WELL.
BUT IT'S MORE KIND OF, YOU KNOW,
ICING AROUND THE CAKE AS OPPOSED
TO THE REAL MEAT OF THE PROBLEM.
SO WHAT YOU DO IN ATTRACTING
PEEL
PEOPLE TO WORK IN THE DISEASES,
YOU CAN'T IMAGINE HOW IMPORTANT
IT IS.
IT IS DISEASE ORGANIZATIONS THAT
HAVE THE IMPACT ON THE YOUNG
SCIENTISTS, IN TERMS OF WHAT
THEY ARE GOING TO STUDY.
WE ALSO PUT MONEY, OTHER THINGS
YOU CAN SEE, PUT MONEY INTO
TRAINING.
WE HAVE NETWORKS FOR CLINICAL
TRIALS.
WE HAVE -- THESE ARE NETWORKS
FOR TRIALS THAT ARE OCCURRING AT
FAIRLY HIGH VOLUME.
YOU WOULDN'T SET A NETWORK UP
FOR A TRIAL WHERE YOU DO ONE
EVERY FIVE YEARS.
BUT IF YOU'RE DOING FIVE TRIALS
SIMULTANEOUSLY THAT WOULD BE A
GOOD PLACE TO DO A NETWORK.
THE FIRST NETWORK WE PUT
TOGETHER WAS FOR EMERGENCY
RESEARCH.
AND THAT WENT REALLY WELL.
SECOND WAS CALLED NEURONEXT,
PHASE 2 FIRST-IN-HUMAN TRIALS,
ANY NEUROLOGICAL CONDITION.
THAT ALSO WORKED WELL,
STRUGGLING A LITTLE NOW TO GET
GOOD APPLICATIONS IN.
WE THINK BECAUSE OF TREATMENTS
COMING OUT NEURONEXT WAS GOING
TO SERVE A GREAT PURPOSE.
WE HAVE A NETWORK FOR STROKE
TRIALS, S IN NINDS STANDS FOR
STROKE.
IT IS THE THIRD -- FOURTH
LEADING CAUSE OF DEATH IN THE
U.S.
AND THERE IS NO COMPANY IN THE
COUNTRY INTERESTED IN STROKE.
THAT'S A REALLY COMMON DISEASE,
KILLS PEOPLE, CAUSES GREAT
DISABILITY, AND NO COMPANY
INTEREST.
THAT'S NOT BECAUSE THEY CAN'T
MAKE MONEY BUT BECAUSE THEY HAVE
SPENT SO MANY BILLIONS OF
DOLLARS IN SALES IN THE 199
0s, EARLY 2000s.
HAVING BEEN A STROKE PERSON THAT
FAILED, IF YOU GO INTO SOMETHING
AND YOU RUN A BIG PROGRAM AND
YOU RUN TEN TRIALS AND THEY ALL
FAIL, THE COMPANIES WILL LEAVE
AND THEY ARE NOT COMING BACK FOR
ANOTHER 10, 20 YEARS, IF YOU'RE
LUCKY.
SO FAILED TRIAL IS A BAD THING.
TEN FAILED TRIALS COULD BE A
TOTAL DISASTER TO A FIELD.
YOU'VE GOT TO BE VERY CAREFUL US
A MOVE INTO THESE SPACES.
THE COMPANIES, YOU WATCH THEM,
VERY MUCH LIKE LEMMINGS, MOVE IN
A GROUP, WILL JUMP OFF A CLIFF
IN A GROUP.
BUT THEY ARE SMARTER, THEY WON'T
JUMP OFF A CLIFF TWICE.
YOU WANT TO WORK CAREFULLY IN
THIS SPACE, JUST BECAUSE OF
THOSE EXPERIENCES.
THAT'S HOW YOU GET A COMPANY --
A COMPANY DROPS IN THE AREA OF
SCIENCE, BECAUSE THEY HAVE LOST
SO MUCH MONEY TRYING TO TEST
THERAPY IN A PHASE 3 TRIAL AND
THEN THE PHASE 3 TRIAL FAILS.
WE HAVE BEEN REALLY FORTUNATE TO
HAVE RECEIVED A LOT OF TAXPAYER
MONEY OVER THE LAST COUPLE
YEARS.
BASICALLY SINCE I BECAME
DIRECTOR OUR BUDGET HAS PROBABLY
DOUBLED.
WE MANAGED NOW CLOSE TO $3
BILLION, AND THE THING ABOUT THE
MONEY IS THAT ABOUT A BILLION OF
THOSE DOLLARS ARE
CONGRESSIONALLY MANDATED
PROJECTS.
SO IT USED TO BE THAT CONGRESS
WOULD INCREASE THE MONEY TO NIH,
VERY STANDARD FASHION, EACH
INSTITUTE WOULD GET THE SAME
INCREASE, MAYBE CANCER WOULD
PROBABLY GET MORE.
WHAT HAPPENED AFTER THE 12 YEARS
OF FLAT FUNDING THAT ENDED IN
2016, WE DID START TO GET
INCREASES BUT WE ALSO GOT
SPECIAL PROGRAMS THAT CONGRESS
PUT FUNDING INTO AND SO THAT
WAS -- THAT'S GOOD IF YOU'RE IN
ONE OF THOSE PROGRAMS.
FOR US, WE WERE LUCKY BECAUSE
MOST OF THE PROGRAMS WERE IN
NEUROLOGICAL DISEASES.
SO, THE FUNDING FOR DEMENTIA
RESEARCH INCREASED BY $3 BILLION
OVER FIVE YEARS.
WE MANAGE 10% OF THAT MONEY,
THAT'S NOT SEEN ON THIS TABLE,
$3 MILLION A YEAR.
BRAIN INITIATIVE IS A
MAGNIFICENT PROJECT TO
UNDERSTAND HOW BRAIN CIRCUITS
WORK.
AND JUST MAYBE WE'LL GET INTO
THAT IN A COUPLE SLIDES DOWN
FROM NOW, BUT THE PREFACE IS
ANYONE WITH A NEUROLOGIC
DISEASE, THE SYMPTOMS ARE DUE TO
ALTERED CIRCUIT.
IN THE PAST WE COULD NEVER LOOK
AT THOSE CIRCUITS AND SEE WHAT
THEY WERE DOING OR HOW THEY WERE
NOTE FUNCTIONING.
BUT NOW THE TECHNOLOGIES ARE
COMING.
THAT'S GOING TO REVOLUTIONIZE
HOW WE DO THERAPEUTIC STUFF.
PARTICULARLY SOME DIAGNOSTICS.
THE HEAL INITIATIVE IS A PROGRAM
IN RESPONSE TO THE OPIOID
CRISIS.
AND WE RUN THE PORTION RELATED
TO DEVELOPING NON-ADDICTIVE PAIN
THERAPIES.
NOT ONLY NEW THERAPIES BUT
BETTER USING REDUCING THERAPIES
TO REDUCE CHANCE OF ADDICTION,
ABOUT $280 MILLION.
AND THEN WE ALSO HAVE TAKEN OVER
THE MANAGEMENT OF THE
UNDIAGNOSED DISEASE NETWORK.
SO THAT WAS RUN OUT OF THE
COMMON FUND WHICH WAS OFFICE OF
THE DIRECTOR, DR. COLLINS'
OFFICE.
THOSE PROGRAMS RUN FOR TEN
YEARS, A REALLY GREAT PROGRAM,
ACROSS THE COUNTRY, WHERE MOSTLY
KIDS BUT COULD BE ADULTS WHO
HAVE DISORDERS THAT NO ONE CAN
DIAGNOSE, THEY CAN APPLY.
PEOPLE LOOK AT THE RECORDS.
THEY SEE IF IT LOOKS LIKE
THERE'S A CHANCE THEY CAN HELP.
THE ONES THEY CAN, THEY BRING IN
AND THERE'S A WHOLE TEAM THAT
FROM AROUND THE COUNTRY INVOLVED
IN TRYING TO UNDERSTAND WHAT'S
THE PROBLEM IS.
THAT'S LED TO A SIGNIFICANT
PROPORTION OF NEW DIAGNOSES AND
DISCOVERY OF A NUMBER OF NEW
GENETIC DISEASES.
AND I SHOULD HAVE SAID IN THE
BEGINNING 400 DISEASES WE HAVE,
THE NUMBER, MAJORITY ARE
NEUROGENETIC DISEASES.
AND SO AS YOU'LL SEE WE'RE
REALLY INTERESTED IN MOVING INTO
THAT GENE THERAPY SPACE.
THE BRAIN INITIATIVE, I DID
MENTION.
AND I MEAN, I'M THE NEW SURE --
IT'S COMPLICATED TO GO THROUGH
IT ALL BUT JUST AN EXAMPLE, WE
CAN NOW IN A MOUSE IDENTIFY A
NEURON GROUP THAT'S RESPONSIBLE
FOR SOMETHING.
THEY AIM.
WE CAN FIND THOSE NEURONS AND
TURN THEM OFF, ANIMALS HAVE NO
-- PAIN DOES NOT BOTHER THEM
ANYMORE.
THEY WILL STILL FEEL IT BUT IT
DOESN'T CAUSE ANY SUFFERING.
SUCH A POWERFUL ABILITY TO DO
THINGS LIKE THAT.
YOU CAN DO THAT FOR MANY
DIFFERENT CORE FEATURES OF
NEUROLOGY.
APPETITE, PAIN, DEPRESSION.
TREMOR, OBSESSIVE COMPULSIVE
DISORDERS, ALL BEING TARGETED IN
THAT POSITION.
THESE ARE JUST IN MICE WHERE YOU
HAVE THIS CONTROL OVER NEURONS.
BUT THE IDENTIFICATION OF THE
CIRCUIT ALLOWS YOU TO DO OTHER
THINGS USING ELECTRICAL
STIMULATION, FOR INSTANCE, TO
TURN OFF PATHWAYS RESPONSIBLE
FOR THE PATIENT'S SUFFERING.
IN THE MOUSE, NEW GENE
THERAPIES, YOU CAN GET THEM,
TURN THE NEURONS ON AND OFF.
AND WE TALK ABOUT GENE THERAPY
FOR RARE NEUROGENIC DISORDERS.
I THINK IT WAS MENTIONED THIS
MORNING THAT IF YOU LOOK AT THE
FUTURE, THIS IS JUST THE
BEGINNING.
THESE DISORDERS YOU HEARD ABOUT,
THESE DISORDERS ARE BEGGING FOR
THESE KIND OF THERAPIES, BUT
ONCE THEY ARE SHOWN TO BE SAFE,
THESE SAME TREATMENTS WILL BE
USED FOR MORE COMMON DISEASES.
BUT THAT'S PROBABLY I WOULD SAY
MAYBE ANOTHER DECADE DOWN THE
LINE.
IN TERMS OF MOVING INTO GENE
THERAPY YOU HEARD THIS MORNING
ABOUT BESPOKE GENE THERAPY
CONSORTIUM THAT WE WORK WITH
NCATS ON.
WE ALSO CO-LEAD WITH NCATS
SOMATIC CELL GENE EDITING
PROGRAM.
THE AMP PROGRAM, REMEMBER THAT
IS TRYING TO WORK WITH THE FDA
TO DEVELOP A PLATFORM TO USE
THIS VIRUS, AAV VIRUS, YOU CAN
PACKAGE THE DIFFERENT GENES?
AND THE IDEA IS IF YOU CAN BUILD
THE PLATFORM, YOU CAN JUST
SWITCH IN THE GENE OF YOUR
INTEREST, WHATEVER THE DISEASE
IS, THAT THINGS WILL MOVE MORE
QUICKLY AND LESS EXPENSIVE.
THAT'S THE IDEA BEHIND THAT.
AN INTERESTING PROJECT,
COMPANIES INVOLVED, ACADEMIA,
FUNDING ACTUAL CLINICAL TRIALS,
AND DR. SILVERTHORN IS BUILDING
A ROAD MAP, FOCUSED ON
PARTICULAR GENES, GENETIC
DISORDERS, BUT THE ROAD MAP IS
GOING TO BE WIDE OPEN, ALLOWING
OTHER PEOPLE TO FOLLOW IT.
UNDIAGNOSED DISEASE NETWORK I
MENTIONED.
WE DIDN'T TALK ABOUT THE URGENT
NETWORK, AN NINDS PROGRAM, TO
DEVELOP GENE THERAPIES, GENOMIC
THERAPIES, FOR REALLY RARE
NEUROLOGICKISTAL DISORDERS RUN
OUT OF NEURONEXT.
THE IDEA IS THE THE MOVEMENT OF
GENE THERAPIES AT THE NEURONEXT
WILL ALLOW THAT NETWORK TO
BECOME MORE POWERFUL IN TERMS OF
TYPES OF TREATMENT IT CAN TEST.
I WANTED TO -- BEFORE I GET OFF
THESE FUTURE-LOOKING PROJECTS, I
WANT TO MENTION IN ALL THESE
AREAS, THE TECHNOLOGIES THAT ARE
REALLY POWERFUL OFTENTIMES
REQUIRE BRAIN TISSUE.
SO, YOU KNOW, WE USED TO LOOK,
IT WAS ALWAYS IMPORTANT, LOOK
UNDER MICROSCOPE, WOULD SEE WHAT
CELLS ARE DOING WHAT, WHAT CELLS
ARE DYING, WHAT LOOK DIFFERENT.
NOW TOOLS ALLOW SINGLE CELL
ANNUAL SILLS OF BRAIN TISSUE,
YOU CAN GET QUANTITATIVE ABOUT
WHAT'S MISSING, WHAT GENES HAVE
BEEN TURNED ON, WHAT THE PROBLEM
IS.
YOU CAN SEE CELLS COMPLETELY
NORMAL, ABOUT TO DIE, A LITTLE
SICK, OTHERS ARE REALLY SICK,
NOT AVAILABLE FIVE YEARS AGO.
THERE'S A HUGE PREMIUM ON BRAIN
TISSUE FOR ALL THESE DISEASES
NOW.
AND A BIG PUSH IS TO APPLY
SINGLE CELL TECHNOLOGIES TO
ALMOST EVERY BRAIN DISEASE YOU
CAN IMAGINE.
HATS OFF TO TISCH, HELPING US IN
TERMS OF GETTING BRAIN TISSUE,
SHE COULD USE YOUR HELP.
EVERYBODY ELSE IN THE AUDIENCE.
BECAUSE THIS IS REALLY GETTING
TO BE A BOTTLE NECK IN GETTING
THE SCIENCE DONE.
OKAY.
ONE PROBLEM THAT CAME UP IN THE
ETHICS SESSION IS THE ISSUE OF
NEURAL HEALTH EQUITY.
SO, A LOT OF THINGS PEOPLE ARE
DOING IS SOPHISTICATED SCIENCE,
SOPHISTICATED WORK.
AND IT TENDS TO BE FOCUSED IN
THESE CERTAIN ACADEMIC
INSTITUTIONS, CERTAIN CITIES IN
OUR COUNTRY, BUT THAT LEAVES 98%
OF THE PEOPLE OUT OF THE BALL
GAME.
WE'RE TRYING REALLY HARD TO LOOK
AT HOW TO REALLY BUILD SPOKES,
ALL THESE DIFFERENT PROGRAMS WE
HAVE, SO THERE'S -- MORE PEOPLE
WILL BE ACCESSIBLE TO THE
RESEARCH PROGRAM.
WE HAVE A GOOD OPPORTUNITY IN
THE ALS, WE'RE ABOUT TO LAUNCH
IN THAT AREA, HOPEFULLY THE
OTHER THINGS AS WELL.
BUT I THINK GOING FOREWARD,
THERE'S GOING TO BE, YOU KNOW, A
REAL IMPRIMATUR ON MAKING THESE
THERAPIES AVAILABLE FOR PEOPLE
IRREGARDLESS OF WHERE THEY LIVE
AND WHAT SOCIOECONOMIC STATUS
IS.
AND THAT'S PROBABLY NOT
SOMETHING THAT NIH IS GOING TO
BE TOO -- WE WON'T HAVE LEVERS
TO DO MUCH IN THAT SPACE.
YOU FOLKS THINK ABOUT IT,
TALKING TO CONGRESS FOLKS,
GETTING THIS ON THE TABLE IS
WHAT'S GOING TO MAKE IT HAPPEN.
AND WE'RE HAPPY TO HELP IN ANY
WAY.
BUT I THINK THERE'S GOING TO BE
A LOT OF ECONOMICS THAT COME
INTO THIS, AND THERE GETS TO BE
POLITICS, SO TRYING TO THINK IT
THROUGH AHEAD OF TIME, SOME OF
THESE SOPHISTICATED NON-PROFITS
HAVE DONE THAT.
BUT WE ALSO HAVE PROBLEMS WITH
SOME OF OUR COMMON DISEASES,
EPILEPSY, STROKE, HUGE
DISPARITIES IN THE WAY PEOPLE
ARE TREATED.
AND THEIR RISK FACTORS.
AND THAT ACTUALLY LEADS TO
PROBABLY UNAVOIDABLE DEATH
REALLY.
SO IN STROKE AREA WE'VE DONE A
LOT OF WORK IN TERMS OF
IDENTIFYING IT, NOW WE'RE TRYING
TO PUT A PROGRAM TOGETHER,
RICHARD WILL TALK TO YOU
TOMORROW, WHERE WE DON'T JUST
WRITE HOW BAD IT IS BUT THROUGH
AND DO SOMETHING ABOUT IT.
AND THAT'S REALLY GOING TO BE
OUR FOCUS GOING FORWARD.
THERE IS A NEW DATA MANAGEMENT
AND SHARING POLICY THAT'S COME
OUT OF THE NIH.
AND THIS IS RELEVANT TO THE
GROUP HERE.
SO, WHAT HAPPENED WAS A BIG PUSH
IN THE GOVERNMENT, TAXPAYER
FUNDS THE RESEARCH, THAT DATA
SHOULD BE AVAILABLE, SHOULDN'T
BE HIDDEN IN SOMEONE'S DRAWER.
A NUMBER OF YEARS AGO NIH SAID,
WELL, STARTING -- TURNS OUT NOW,
BUT THEY SAID THIS YEARS AGO,
NIH-FUNDED RESEARCH HAS TO MAKE
THE DATA AVAILABLE, POST IT
SOMEWHERE.
THE OPPORTUNITY FOR YOU TO THINK
ABOUT HOW TO ORGANIZE THE DATA
THAT'S HELPFUL TO YOUR GROUP.
NIH IS NOT DOING THAT.
THAT PART IS UP TO THE
SCIENTISTS TO FIGURE OUT HOW TO
MAKE THE DATA USEFUL.
GOOD NEWS, WE'RE GOING TO PAY
THEM TO POST THE DATA.
BAD NEWS, SOMEBODY HAS TO
ORGANIZE THEM TO MAKE THE DATA
USEFUL.
BUT IT'S AN OPPORTUNITY I THINK
FOR THE DISEASE ORGANIZATION TO
TAKE LEADERSHIP ROLE, GET FOLKS
TOGETHER AND SAY THEY ARE GOING
TO HAVE TO POST DATA, WHAT
COMMON DATA ELEMENTS WILL YOU
USE, HOW ARE WE GOING TO FIND
IT, CAN YOU TELL US WHERE IT ALL
IS AND WE'LL HAVE A LIBRARY TO
GET THROUGH IT.
TRY AND MAKE THAT DATA USEFUL.
THAT'S WHERE WE ARE.
WE'RE INTERESTED IN HELPING BUT
I DON'T THINK YOU WANT THE
GOVERNMENT TELLING YOU WHAT WE
SHOULD DO IN THIS SPACE.
YOU WANT THE SCIENTISTS AND
DISEASE ORGANIZATIONS TO MAKE
THOSE CALLS.
BUT WE'LL BE PAYING FOR THE
POSTERS, SO TAKE ADVANTAGE OF
THAT.
AND THE LAST SLIDE OF MY GROUP,
AS YOU KNOW DR. COLLINS STEPPED
DOWN, SEEMS LIKE 2 1/2 YEARS AGO
KNOW.
DR. LARRY TABAK, WHO WAS DEPUTY
DIRECTOR, HAS BEEN THE ACTING
SINCE THAT TIME.
AND IT'S A TOUGH JOB.
AND THERE WAS A SEARCH.
AND THE SEARCH DECIDED TO PICK
ON MONICA BERTAGNOLLI "PICK ON"
WAS A FREUDIAN SLIP, PICKED
MONICA BERTAGNOLLI, PICKING ON
HER BECAUSE IT'S SUCH A TOUGH
JOB.
SHE'S THE NCI DIRECTOR
CURRENTLY, IN THE JOB SEVEN OR
EIGHT MONTHS, WAITING FOR THE
SENATE TO KIND OF GET PAST THEIR
POLITICAL THINGS AND ACTUALLY
MAKE A DECISION HERE.
IT'S REALLY IMPORTANT THE NIH
HAVE A DIRECTOR WHO HAS GOOD
RELATIONSHIPS WITH THE CONGRESS
AND I THINK SHE'S GOING TO BE A
REALLY GOOD.
SHE'S A SURGEON FROM
DANA-FARBER.
SURGEONS TEND TO BE NO NONSENSE
PEOPLE, GET THINGS DONE.
THAT WOULD BE FANTASTIC, I
THINK.
THAT'S WHAT I WANTED TO LET
PEOPLE KNOW ABOUT, WHERE WE ARE
IN THE INSTITUTE.
WE'RE REALLY EXCITED ABOUT
THINGS GOING FORWARD.
WE'RE A LITTLE WORRIED ABOUT THE
BUDGET.
WHAT WE'VE BEEN TOLD IS THERE'S
A REASONABLE CHANCE THAT WE'LL
HAVE A FLAT BUDGET.
UNFORTUNATELY THAT'S THE BEST
NEWS WE COULD GET.
BUT THAT PUTS US $40 MILLION IN
THE HOLE, WE'LL HAVE TO CUT
THINGS TO GET BACK TO THE STABLE
STATE.
AND THE REASON IS BECAUSE WHEN
WE FUND THINGS WE FUND THINGS
FOR FIVE YEARS.
SO WE HAVE COMMITMENTS THAT ARE
GOING OUT, THEY GROW OVER TIME.
IF WE HAVE TO CUT THAT WOULD BE
TOUGH.
EVEN FLAT, A LOT OF THINGS WE
HOPED TO DO WE WON'T BE ABLE TO
DO FOR A WHILE.
KIND OF GO INTO A STEADY STATE
MODE.
IF WE HAD A CUT WE WOULD BE IN A
CRISIS MODE.
BUT WE HAVE GOTTEN INCREASES
SINCE 2016.
SO WE HAVE REALLY GOOD RESOURCES
GOING FORWARD.
JUST MIGHT BE A LITTLE BIT OF A
DIP DEPENDING WHAT CONGRESS DOES
THIS TIME.
WE'VE GOT OUR FINGERS CROSSED,
DEFINITELY APPRECIATE YOU
TALKING ABOUT THE IMPORTANCE OF
THIS KIND OF WORK, THAT'S REALLY
WHAT MAKES IT HAPPEN.
ALL RIGHT.
THANKS VERY MUCH.
I'M HAPPY TO ANSWER ANY
QUESTIONS.
WE HAVE A LOT OF PROGRAM
DIRECTORS HERE, PEOPLE WHO DO
ALL THE WORK, I DO E-MAILS AND
THEY DO ALL THE WORK.
AND THEY ARE REALLY FANTASTIC
PEOPLE, REALLY INVESTED AND LOVE
WORKING WITH NON-PROFIT
ORGANIZATIONS.
>> THANK YOU VERY MUCH.
CURE SMA, APPRECIATE YOUR
SUPPORT FOR SMA IN THE PAST AND
COMMITMENT FOR SMA RESEARCH IN
THE FUTURE.
I WANT TO EXPAND UPON YOUR LAST
COMMENT ABOUT THE NIH BUDGET,
PARTICULARLY NINDS BUDGET.
DEBT CEILING DEAL MEANS THAT
LIKE YOU MENTIONED, LEVEL
FUNDING IS UNFORTUNATELY A
VICTORY IN THIS POLITICAL
CLIMATE.
WHAT WOULD BE PART OF YOUR
BUDGET THAT WOULD TAKE THE
BROADEST HIT IF YOU SAW LEVEL
FUNDING OR A CUT BEING PROPOSED
IN THE HOUSE BILL?
>> RIGHT.
WELL, WHAT WE HAVE NOW IS WE
HAVE GROUPS, I MENTIONED THREE
DIVISIONS.
THOSE THREE DIVISIONS ARE NOW
PLANNING ON HOW TO ABSORB FLAT,
WHICH MEANS $40 MILLION DEFICIT,
OR A CUT.
THEY WILL COME UP WITH
RECOMMENDATIONS.
GENERALLY WE -- IT'S OUR
RESPONSIBILITY TO OPERATE IN A
FLAT SITUATION.
IF THE NIH GETS A CUT, I THINK
WHAT WE PROBABLY HAVE TO DO IS
PASS THAT CUT TO ALL THE GRANTS
THAT ARE ACTUALLY OUT THERE AS
WELL AS NEW GRANTS.
IF WE ARE FLAT, WE'LL PROBABLY
TRY TO ABSORB BY DECREASING
AMOUNT OF MONEY THAT'S GOING TO
THE NEW GRANTS.
THEN WE HAVE THIS ISSUE OF, YOU
KNOW, FOR INSTANCE THERE ARE
SOME PEOPLE WHO IF THEY ARE NOT
FUNDED, SAY YOUNG INVESTIGATOR
DOESN'T GET THIS FUNDING, THEY
WILL LEAVE AND WON'T COME BACK.
THEY WILL BE GONE FOREVER.
SO WHAT WE'LL TRY AND PUT
EMPHASIS ON, THE YOUNG
INVESTIGATORS, EARLY-STAGE
INVESTIGATORS, ALSO PEOPLE WHO
HAVE ONLY ONE NIH GRANT, AND
THEY COME REALLY CLOSE TO
GETTING FUNDED BUT THEY DON'T
MAKE THE PAYLINE.
IF THEY DON'T GET A GRANT THEIR
LABS WILL CLOSE AND THEY WILL
LOSE THEIR JOB IN THE LAB, WE'LL
BASICALLY LOOK AT THAT GROUP.
I HATE TO SAY THIS, WE HAVE $72
MULTI-CLINICAL TRIAL WE'D LIKE
TO DO, THAT WOULD BE HARD TO DO
IF WE GOT FLAT BUDGET.
WE MIGHT HAVE TO PUT THAT OFF
UNTIL THE FINANCIAL SITUATION
LOOKS BETTER.
THOSE ARE HARD DECISIONS.
WE WANT TO ACTUALLY KEEP THE
WHOLE ECOSYSTEM HEALTHY AND ALL
THE DIFFERENT ASPECTS, AND
BECAUSE THESE THINGS GO UP AND
DOWN.
YOU DON'T WANT TO DO, IN THE
DOWN SIDE, DO SOMETHING THAT'S
GOING TO HURT YOU FOR TEN YEARS.
>> HI, WALTER, DIANA GRAY, I'M
THE CEO OF THE HYDROCEPHALUS
ASSOCIATION.
THANK YOU.
I'M RIGHT HERE.
THANK YOU FOR THE PRESENTATION.
IF HAD YOU ALL THE MONEY COULD
YOU IMAGINE FOR THE NINDS, WHAT
WOULD YOU DO, WHAT ARE YOU
MISSING, WHAT DO YOU LAY AT WAKE
AND NIGHT AND THINK IF I COULD
JUST HAVE THIS MUCH MORE I COULD
DO X, WHAT WOULD IT BE?
>> BEFORE I GO TO THE MONEY
PART, I'D SAY THAT THE PEOPLE
WHO MAKE IT HAPPEN, SO NOT
NECESSARILY -- YOU DON'T REALLY
BUY THE PEOPLE.
SOMETHING ELSE HAS TO HAPPEN TO
GET THE PEOPLE TO COMMIT TO THIS
KIND OF CAREER.
IT'S OUR JOB TO PURSUE.
IN THAT SPACE WHAT WE KNOW IS AS
I MENTIONED HOW WE FUND THINGS
IS WE FUND THE BEST SCORES UNTIL
WE RUN OUT OF MONEY, AND THERE
ARE CERTAIN AREAS WHERE, SAY,
FOR INSTANCE, THE EARLY-STAGE
INVESTIGATORS, WHERE WE MADE A
COMMITMENT THAT ALTHOUGH WE RUN
OUT OF MONEY AT THE 14th
PERCENTILE GRANT WE'LL FUND
EARLY-STAGE INVESTIGATORS TO 25
BECAUSE WE REALLY HAVE TO INVEST
IN THE EARLY-STAGE
INVESTIGATORS.
SO THEN WE DID ANALYSIS TO SEE,
WELL, IS THERE ANY DIFFERENCE
BETWEEN PEOPLE WHO GOT BELOW 14
VERSUS 23?
NO DIFFERENCE.
AS A MATTER OF FACT, THE PEOPLE
WHO GOT THE GRANT EARLY, THEY
ARE MAYBE BIG HEAD AND DON'T DO
AS WELL IN THE LONG RUN.
SOME OF THE REAL, YOU KNOW, SOME
OF THE PEOPLE WHO REALLY WORK
HARD AND KEEP PERSISTING, THEY
SOMETIMES DO BETTER.
SO WHAT WE KNOW EVERY TIME WE'VE
LOOKED, THAT ABOVE WHERE WE FUND
PEOPLE ARE JUST AS GOOD AS THE
PEOPLE WHO GOT IN RIGHT UNDER
THE FUNDING.
WE LEAVE A LOT OF GOOD RESEARCH
ON THE TABLE, THAT'S FOR SURE.
AND THEN WE HAVE BEEN ABLE TO DO
CERTAIN THINGS FOR CERTAIN
REASONS THAT HAPPEN TO US.
SO WE HAVE LIKE THE BRAIN
INITIATIVE, WE HAVE HEAL
INITIATIVE, ALS PROGRAM.
WE COULD -- THEY ARE REALLY GOOD
PROGRAMS, WE COULD DO THOSE IN
OTHER DISEASES IF WE HAD THE
MONEY.
I THINK BUILDING THE
PARTNERSHIPS HAVE BEEN REALLY
THINK A POWERFUL TOOL FOR US TO
BUILD PARTNERSHIPS WITH THE
NON-PROFITS AND THE INDUSTRY
AROUND A CERTAIN AREA.
WE HAVE ONE IN PARKINSON'S,
ACCELERATED MEDICINE
PARTNERSHIP.
NOW WE'RE BUILDING ONE IN ALS.
AND THEN WE HAVE, YOU KNOW,
NETWORKS THAT HAVE BEEN REALLY
QUITE PRODUCTIVE THAT WE THINK
WE COULD GET MORE THERAPIES IN.
WE COULD REACH OUT TO BIOTECH
COMPANIES MORE, TRY AND PULL
THEM IN, PARTICULARLY IN THE
DISEASES THAT ARE SEEN AS HIGH
RISK.
WE COULD DO MORE THERE.
THE SMALL BUSINESS GRANTS, WHEN
I CAME, YOU KNOW, SMALL BUSINESS
GRANT WAS AN EASY WAY TO GET
MONEY.
IT WASN'T THAT COMPETITIVE.
NOW SMALL BUSINESS GRANTS ARE
REALLY GOOD NOW.
SO, AGAIN, I THINK OUR FIELD IS
GROWING AND MUCH MORE WE CAN DO.
THERE'S NOT ONE THING I WOULD
SAY WE WOULD DO WITH THE MONEY
BUT I THINK WE -- YOU KNOW, WHAT
WE USED TO SAY, REALLY TRUE,
THINGS ARE GOING WELL, THEY
COULD GO FASTER IF WE HAD MORE
MONEY.
>> IT'S AN EASY ONE.
I'M STILL STRUCK BY THE JUST
HOPE FOR THE WHOLE NEUROLOGICAL
SPACE.
FROM WHERE IT WAS 10 TO 20 YEARS
AGO, 90% FAILURE RATES IN
CLINICAL TRIALS, THERE'S A LONG
ROAD AHEAD BUT I'M INCREDIBLY
HOPEFUL.
YOU'VE GOT 400 DISEASES IN YOUR
PORTFOLIO, THE QUESTION OF WHO
IS GOING TO PAY FOR THOSE DRUGS
IS NOT YOURS TO ANSWER BUT
REFLECT FROM YOUR EXPERIENCE AND
POSITION, IT FEELS LIKE AS WE DO
GET SUCCESS FOR ALL THE RARE
DISEASES WHICH ARE GOING TO CHIP
AWAY MORE AND MORE AS WELL AS
MASSIVE ONES LIKE ALZHEIMER'S,
THAT ARE NOT RARE BUT HAVE
PREVIOUSLY NOT REALLY BEEN PAID
FOR, WE NEED TO RESET HOW WE PAY
FOR ALL DRUGS.
I DON'T KNOW THE ANSWERS TO THAT
BUT I'D LOVE TO THROW IT AT YOU
AND HEAR YOUR WORDS OF WISDOM
FOR A FEW MINUTES.
>> RIGHT.
THE WAY I THINK ABOUT IT IS THAT
THE GREAT THING ABOUT OUR JOB IS
THAT WE TAKE PROBLEMS THAT HAVE
NO SOLUTIONS AND TRY TO GET A
SOLUTION FOR IT.
AND THEN THE QUESTION COMES,
WHAT IS THE -- WE THROW IT OVER
THE FENCE
WHAT IS THE COMMUNITY GOING TO
DO ABOUT IT?
SOMETIMES WE CAN HELP IN THAT
SPACE.
AND -- BUT THE DISEASES THAT
WE'RE TALKING ABOUT ARE NOT THE
KIND OF THINGS PEOPLE CAN
IGNORE.
SO I'M VERY CONFIDENT THAT I
DON'T KNOW THE ANSWER BUT I
THINK PEOPLE WILL FIND A WAY TO
DO ANY A LESS EXPENSIVE WAY, TO
MAKE IT MORE ACCESSIBLE, BECAUSE
THIS IS JUST NOT RIGHT THAT IT'S
NOT DONE.
AND MY EXPERIENCE, I WORKED IN
HUNTINGTON'S.
AND WE HAD A LOT -- WE FOUND THE
GENE, THOUGHT WE WOULD HAVE A
TREATMENT IN TEN YEARS, IT'S NOW
25 YEARS, AND NO TREATMENT.
BUT THEN I WORKED IN STROKE,
BASICALLY WORKED AT TAKING CLOTS
OUT OF PEOPLE WITH ACUTE STROKE,
IT WAS LIKE A MIRACLE.
NOW WE HAVE, YOU KNOW, NOW IT'S
GONE ACROSS THE COUNTRY.
WHEN I STARTED, YOU COULDN'T GET
ANYBODY TO TAKE A STROKE PATIENT
ON THE TEAM BECAUSE IT WAS SUCH
A TERRIBLE OUTCOME.
YOU HAVE ONE OF THESE LARGE
CLOTS, YOU'RE DEAD.
NOW IT'S COMPLETELY CHANGED.
THE WHOLE SYSTEM IS CHANGED.
FROM MY EXPERIENCE, THERE'S
NOTHING LIKE AN EFFECTIVE DRUG
TO ACTUALLY CHANGE THE HEALTH
CARE SYSTEM.
YOU CAN DO EVERYTHING YOU WANT,
IF THERE'S NO TREATMENT, IT
SEEMS LIKE THE YOU CAN ONLY MAKE
INCREMENTAL CHANGES.
ONCE YOU HAVE A NEW TREATMENT IT
FORCES CHANGE AND USUALLY -- IN
OUR COUNTRY STROKE, IT WORKED
OUT FOR THE PEOPLE IN THE
COUNTRY.
NOT EVERYBODY.
IT'S STILL NOT EQUALLY
ACCESSIBLE.
AND THAT WAS A BIG THING.
HAD YOU TO TREAT PEOPLE WITHIN
THREE HOURS OF A STROKE.
THERE'S NO WAY THAT COULD EVER
HAPPEN BUT NOW IT'S ROUTINE.
SO I THINK IF YOU GET SOMETHING
THAT WORKS, THE SYSTEM WILL
FIGURE OUT ITS WAY AREN'T.
NOW, THE MONEY SIDE, THAT'S
DIFFERENT.
IT'S NOT JUST US.
IT'S THE CANCER DRUGS,
RHEUMATOLOGY DRUGS, BIOLOGICS,
AND, YOU KNOW, THINK THAT'S
GOING TO REQUIRE A CHANGE IN THE
WAY THE COUNTRY LOOKS AT THINGS.
I DON'T THINK THEY ARE GOING TO
LEAVE PEOPLE UNTREATED.
>> I HAVE A QUESTION.
MORE OF A COMMENT.
BRANDY, CO-FOUNDER OF SUPPORT
FIBROMYALGIA, ESTABLISHED
SHORTLY AFTER BEING DIAGNOSED,
MY MOM IN THE '90s WHEN IT WAS
COMING INTO THE MEDICAL FIELD.
ONE OF THE DISAPPOINTMENTS I HAD
WAS THERE WAS NOT MUCH OF A
DIFFERENCE BETWEEN THE TREATMENT
METHODS THAT MY MOTHER RECEIVED
AND IN '90s AND WHAT I
RECEIVED IN 2012.
WE CREATED THE NON-PROFIT
FIBROMYALGIA TO HOPE OF GETTING
MORE RESEARCH FOR FIBROMYALGIA
AND GIVE THE COMMUNITY HOPE
THERE ARE PEOPLE FIGHTING TO GET
ADVANCEMENTS IN TREATMENT AND
HELPING OUR PROVIDERS.
SO THIS IS MORE OF A COMMENT TO
SAY WE APPRECIATE THIS
OPPORTUNITY TO BE ABLE TO
CONNECT WITH RESEARCHERS AND
CONNECT WITH OTHER NON-PROFITS
TO LEARN HOW WE CAN FURTHER
THOSE EFFORTS.
THAT'S WHAT I JUST WANTED TO
SAY.
>> I REALLY APPRECIATE THAT.
AND CERTAINLY WE ARE NOW LEADING
THE PAIN RESEARCH FOR THE HEAL
INITIATIVE, AND TRYING TO BUILD
FROM LOW LEVEL A STRONG PAIN
RESEARCH STRUCTURE AND HOPE IT
CAN HELP WITH YOU FIBROMYALGIA.
OKAY.
THINK WE'RE GOOD.
IT WAS A REALLY GREAT DAY, I
MUST SAY.
>> THANK YOU, WALTER.
WE HAVE POSTERS.
WE HAVE DIVISION DIRECTORS.
WE HAVE LEADERSHIP AND PROGRAM
DIRECTORS TO TALK WITH YOU.
WE CAN CONTINUE THE MEETING,
CONTINUE THE CONVERSATION IN THE
POSTER SPACE.
TOMORROW AT 10:00 WE'LL START
PROMPTLY AT 10:00 TOMORROW.
>> GREAT.
>> THANK YOU.
>> THANKS, EVERYONE.