>>I WOULD LIKE TO WELCOME THE
MEMBERS OF THE COMMITTEE, THE
NCI STAFF, AND GUESTS. I WOULD
LIKE TO REMIND YOU AS COMMITTEE
MEMBERS YOU MUST ABSENT
YOURSELVES DURING SPECIFIC
DISCUSSIONS WHEREVER YOU FEEL
YOUR PARTICIPATION AND
DELIBERATIONS ARE OF PARTICULAR
PRODUCT, PROGRAM OR OTHER
SPECIFIC MATTER WOULD CONSTITUTE
A CONFLICT OF INTEREST OR CREATE
THE APPEARANCE OF ONE. WE ARE
ALWAYS THE BEST JUDGE OF WHETHER
WE ARE IN CONFLICT. SO I
ENCOURAGE YOU. IT IS INCUMBENT
UPON YOU TO ADVISE THE EXECUTIVE
SECRETARY, DR. LODEK LOPACZYNSKI
AND ABSTAIN FROM ANY DISCUSSION
OR ACTION REGARDING THAT MATTER.
IN KEEPING WITH CURRENT
POLICIES, CONFLICT OF INTEREST
BASED ON FINANCIAL HOLDINGS OF
SPECIAL GOVERNMENT EMPLOYEES
WHICH CATEGORIES ALL MEMBERS, WE
MUST DEPEND UPON YOU TO
VOLUNTARILY ABSENT YOURSELVES
DURING DISCUSSIONS OF MATTERS
THAT COULD IMPACT THE STATUS OF
THOSE HOLDINGS. WE TRUST YOUR
JUDGMENT IN THESE INSTANCES.
MEMBERS OF THE PUBLIC WHO MAY
WISH TO EXPRESS VIEWS REGARDING
ITEMS DISCUSSED DURING TODAY'S
MEETING MAY DO SO IN WRITING TO
DR. LOPACZYNSKI, EXECUTIVE
SECRETARY OF THE COMMITTEE
WITHIN TEN DAYS AFTER THE
MEETINGING. ANY WRITTEN STATEMES
BY MEMBERS OF THE PUBLIC WILL
RECEIVE CAREFUL CONSIDERATION.
BY LAW, A QUORUM OF COMMITTEE
MEMBERS IS REQUIRED FOR EACH
INSTANCE IN WHICH A VOTE OCCURS
DURING TODAY'S MEETING A MINIMUM
OF 7 APPOINTED MEMBERS MUST BE
PRESENT TO VOICE THEIR VOTES.
SINCE WE CANNOT PREDICT TIME OR
OCCURRENCE OF ANY MOTION, YOUR
PRESENCE IS A MUST FOR ALL
SEGMENTS OF THE MEETING. DO WE
HAVE A QUORUM?
>>LET ME DOUBLE CHECK WITH JOY.
>>YES.
>>WE ARE GOOD.
>>SO WE DO HAVE SEVEN MEMBERS.
>>PERFECT. WITH THAT, DO I HAVE
A MOTION TO APPROVE MINUTES FROM
THE LAST FNLAC MEETING ON JUNE
27, 2022? MOTION TO APPROVE? DID
SOMEONE RAISE --
>>MOTION.
>>OKAY. SECRET OKAY. SECOND?
>>I'LL SECOND.
>>ANY DISCUSSION? ALL THOSE IN
FAVOR? AYE. ANYONE OPPOSED? OR
ABSTENTIONS? THANK YOU. JUST TO
DRAW YOUR ATTENTION TO THE
FUTURE MEETING DATES YOU CAN SEE
THE DATES LISTED ON YOUR AGENDA,
THERE WILL BE A VIRTUAL MEETING
OUR NEXT MEETING WILL BE
VIRTUAL, ON FEBRUARY 27, MARK
YOUR CALENDARS ACCORDINGLY. WE
WILL ACTUALLY HOPEFULLY BE LIVE
IN PERSON NEXT JULY 10 THROUGH
11, HOPEFULLY THAT WILL HAPPEN,
BE NICE TO SEE PEOPLE IN PERSON.
OUR FIRST ITEM OF TODAY, IS THE
NCI PRINCIPLE DEPUTY DIRECTORS
REPORT BY DR. DOUG LOWY.
>>THANK YOU SO MUCH. GOOD
MORNING, EVERYONE. THANK YOU,
VERY MUCH FOR JOINING AND IT IS
A PLEASURE TO TALK WITH YOU ONCE
AGAIN PERHAPS FOR THE LAST TIME
AS DEPUTY DIRECTOR. I'M HOPING
THAT WHEN WE MEET IN FEBRUARY,
THAT DR. BERTAGNOLLI WILL NOT
ONLY HAVE BEEN AT THE HELP FOR A
SUBSTANTIAL TIME PERIOD BUT SHE
WILL FEEL MUCH BETTER THAN SHE
IS TODAY. IF I COULD HAVE THE
NEXT SLIDE PLEASE. I'M GOING TO
COVER A FEW ISSUES TODAY. FIRST
I WANT TO WELCOME THE FIVE NEW
MEMBERS OF THE FNLAC COMMITTEE.
MARY HENDRIX, RODNEY HO CAROL
BOLT AND ANGELA GRONENBORN. I
WANT TO POINT OUT FOR ANGELA,
THIS IS HER SECOND TIME AROUND
AFTER A PERIOD NOT BEING A
MEMBER OF THE FNLAC. AND
AFANTASTIC MADABHUSHI. IT IS A
SPECIAL PLEASURE TO WELCOME
ANGELA BACK ONCE AGAIN. I'M
GOING TO COVER FOUR DIFFERENT
ISSUES, ONE IS ABOUT NCI NEWS
THEN A FEW RESEARCH ADVANCES
CANCER MOON SHOT THEN ENDING
WITH BUNCH OF UPDATES ANNUAL
PLAN BUDGET PAROLE FOR FY 24 AND
ALTHOUGH FY 23 IS ONLY 12 DAYS
OLD, THIS IS ONE OF THE FEW
THINGS THAT THE NCI DOES LONG IN
ADVANCE. NEXT SLIDE PLEASE. AS
I ASSUME ALL OF YOU KNOW, MONICA
BERTAGNOLLI STARTED A WEEK AGO
AS THE NCI DIRECTOR AND SHE IS A
POSITIVE FORCE, HAS HIT THE
GROUND RUNNING. SHE IS NOT HERE
DOWN IN BETHESDA TODAY BECAUSE
SHE'S NOT FEELING THAT WELL BUT
NEVERTHELESS SHE IS GOING TO SAY
A FEW WORDS TO YOU AFTER MY
PRESENTATION. SHE AND I ARE
GOING TO TAKE YOUR QUESTIONS
AFTERWARDS. SHE AND I HAVE
AGREED IF THEY ARE EASY
QUESTIONS I WILL ANSWER THEM AND
IF THEY ARE DIFFICULT QUESTIONS
SHE WILL ANSWER THEM. NEXT SLIDE
PLEASE. SO I WANT TO UPDATE YOU
ON THE RECOMPETITION. REQUEST
FOR PROPOSALS WAS RELEASED THE
END OF JUNE AND THE CURRENT
PROPOSAL DUE DATE IS MID
FEBRUARY. WE ARE PLANNING FOR A
PRE-PROPOSAL CONFERENCE SOMETIME
IN THE NEXT COUPLE OF MONTHS. WE
ARE ALSO DEVELOPING PLANS FOR IN
PERSON TOUR OF THE NCI FREDERICK
SPACE AT FORT DEE TRI DEITRICK.E
AWARD DATE IS SOMETIME IN 2024.
BECAUSE THE TIME LINE IS
SUBSTANTIAL. WE ARE MAKING EVERY
EFFORTS FOR THIS TO BE AN OPEN
COMPETITION FOR THE FREDERICK
CANCER RESEARCH FACILITY. NEXT
WEEK IS GOING TO BE THE FOURTH
RAS INITIATIVE SYMPOSIUM. IT IS
A THREE DAY MEETING, THE LAST
RAS SYMPOSIUM WHICH WAS
ESSENTIALLY TWO YEARS AGO WAS A
VIRTUAL MEETING. IT WAS ATTENDED
BY MORE THAN 1500 PEOPLE NOT
JUST IN THE UNITED STATES BUT IN
MANY OTHER COUNTRIES AS WELL.
THE RAS INITIATIVE IS COMING UP
FOR REREVIEW. YOU ALL AT FNLAC
WILL BE DISCUSSING THE OUTCOME
OF THAT REVIEW WHEN YOU MEET IN
FEBRUARY. THE RAS SYMPOSIUM WILL
BE IN PERSON AND MONICA IS GOING
TO BE OPENING THE MEETING THIS
COMING MONDA MONDAY. IT SHOULD A
VERY EXCITING MEETING. IT ALSO
WILL BE AVAILABLE VIRTUALLY FOR
THOSE WHO CAN'T COME BUT WHO
MIGHT WANT TO PARTICIPATE. YOU
HEARD FROM RICH VOLKERS A COUPLE
OF MEETINGS AGO ABOUT THE FNLCR
AWARENESS CAMPAIGN. THERE IS
GOING TO BE A NEW VIDEO MARKING
TEN YEARS OF THE FREDERICK
NATIONAL LABORATORY. THERE ALSO
IS GOING TO BE A CANCER CURRENTS
BLOG AT THE NCI WEBSITE NEXT
MONTH. ALSO A SURVEY OF
EXTRAMURAL RESEARCHERS TO FIND
OUT HOW WELL KEPT IS THE SECRET
OF THE FREDERICK NATIONAL
LABORATORY. HOPEFULLY AT LEAST
SOME OF THEM WILL HAVE HEARD
ABOUT IT. THERE ARE GOING TO BE
SOME PRESENTATIONS TODAY TALKING
ABOUT SOME OF THE ACTIVITIES
GOING ON AT FREDERICK NATIONAL
LABORATORY. A COUPLE OF WEEKS
AGO MONICA WAS INVOLVED IN
ORGANIZING A MEETING BEFORE SHE
BECAME NCI DIRECTOR OF A WHITE
HOUSE FORUM ON CHILDHOOD CANCER.
IT WAS WIDELY ATTENDED A SERIES
OF PANEL DISCUSSIONS AND IT WAS
A HIGHLY INFORMATIVE MEETING AND
DISCUSSING A LOT ABOUT THE SATE
OF THE ART OF CHILDHOOD CANCER
RESEARCH AROUND IMPLEMENTATION.
A NUMBER OF SPECIFIC ISSUES FOR
THE WAY FORWARD. GREG RIEMAN WHO
HAS BEEN AT THE FDA FOR A LONG
TIME FOCUS ON CANCER RESEARCH
ISSUES AND FDA APPROVALS IS
GOING TO BE THE SCIENTIFIC
DIRECTOR OF THE NCI CHILDHOOD
CANCER DATA INITIATIVE. HE WAS
ONE OF THE PEOPLE AND STEVEN
CHANNICK HEAD OF INTRAMURAL
DIVISION OF CANCER EPIPEOPLOLOGY
AND GENETICS WAS ON THE A
DIFFERENT PANEL. JUST A FEW
UPDATES MANY ARE AWARE OF THE
ENORMOUS ADVANCES MADE FOR
BREAST CANCER WITH HER 2 BUT
COUPLE OF MONTHS AGO THE FDA
GAVE ACCELERATED APPROVAL FOR A
HER 2 INHIBITOR VERSION,
TRASTUZIMAB DEROTECAN. THIS IS
FOR PATIENTS WHO HAVE ABNORMAL
HER 2 EXPRESSION IN THEIR LUNG
CANCER. IT IS FIRST TIME
PATIENTS WITH HR 2 MUTANT LUNG
CANCER HAVE FDA APPROVED
TARGETED THERAPY OPTION. THIS
ADDS TO THE LONG LIST OF
THERAPEUTIC OPTIONS FOR PEOPLE
WITH LUNG CANCER WHICH HAS
CONTRIBUTED SUBSTANTIALLY TO
DECREASE MORTALITY RATES IN LUNG
CANCER BEYOND INCREASE IN
MORTALITY RATES AS A RESULT OF
SMOKING CESSATION BY ITSELF.
THIS IS SOMETHING THAT MIGHT BE
USEFUL FOR PATIENTS WITH
GLIOMAS. DEPENDENCE ON DE NOVO
NUCLEOTIDE SYNTHESIS AND A DRUG
THAT MAY BE ABLE TO EXPLOIT THIS
VULNERABILITY. THERE'S GOING TO
BE A CLINICAL TRIAL SPONSORED BY
THE GLIAL BLASTOMA THERAPEUTICS
NETWORK. IF YOU WANT MORE
INFORMATION THE PAPER, THE
CITATION IS LISTED AT THE BOTTOM
OF THIS SLIDE. NEXT SLIDE
PLEASE. THIS SLIDE IN MANY WAYS
MULTIPLE MYELOMA IS THE POSTER
CHILD FOR THE NUMBER OF NEW
THERAPEUTIC OPTIONS WHICH HAS
BEEN CORRELATED WITH AN ENORMOUS
INCREASE IN SURVIVAL RATE OF
PATIENTS WITH MULTIPLE MYELOMA.
BUT HERE IS YET ANOTHER
POTENTIAL ADVANCE OF
IMMUNOTHERAPEUTIC DRUG
TECLISAVAW B, IN PEOPLE WITH
MYELOMA THAT THAT HAVE NOT
RESPONDED TO OTHER TREATMENTS
AND NEARLY TWO-THIRDS OF
PARTICIPANTS HAD A PARTIAL
RESPONSE. THIS IS SOMETHING THAT
MAYBE ADDED TO THE ALREADY
SUBSTANTIAL ARMAMENTARIUM FOR
THE TREATMENT OF MULTIPLE
MYELOMA. NEXT SLIDE PLEASE. I
NOW WANT TO SAY A COUPLE OF
SLIDES ABOUT HEALTH DISPARITIES.
WE TALKED A LOT IN THE PAST
ABOUT HEALTH DISPARITIES TRYING
TO OVERCOME THEM WITH A LOT OF
DIRECT PATIENT ENGAGEMENT
COMMUNITY ENGAGEMENT, THE
IMPORTANCE FOR CLINICAL TRIALS
IN THOSE AREAS BUT I WANT HERE
TO TALK ABOUT POTENTIAL
IMPORTANCE OF TECHNOLOGY
DEVELOPMENT AND HEALTH
DISPARITIES AND IT IS
PARTICULARLY RELEVANT FOR THE
FREDERICK NATIONAL LABORATORY
WHICH IS SO HEAVILY ORIENTED
TOWARDS TECHNOLOGY DEVELOPMENT.
IN THE UPPER LEFT RECTANGLE,
WHAT I HAVE SHOWN HERE IS THE
TECHNOLOGY CAN DECREASE
DISPARITIES, INCREASE
DISPARITIES OR BE NEUTRAL. ON
THE BOTTOM LEFT RECTANGLE DON'T
WAIT UNTIL THE END TO CONSIDER
THE POSSIBLE IMPACT ON
DISPARITIES. INSTEAD AS SHOWN IN
THE UPPER RIGHT RECTANGLE TO
INCREASE THE LIKELIHOOD OF
TECHNOLOGICAL DEVELOPMENT,
DECREASING DISPARITIES THINK
ABOUT DISPARITIES FROM THE
BEGINNING OF THE PROCESS. MORE
DIRECT APPROACH COULD BE TO
DEVELOP TECHNOLOGY WHOSE GOAL
INCLUDES REDUCING DISPARITIES.
LAST MONTH I GAVE THE KEYNOTE
ADDRESS AT THE AACR CONFERENCE
ON THE SCIENCE OF CANCER HEALTH
DISPARITIES IN RACIAL ETHNIC
MINORITIES IN MEDICALLY
UNDERSERVED. THESE WERE SOME
TAKE HOME MESSAGES. FIRST WE
HAVE MADE SOME PROGRESS. OVER
THE LAST 20 YEARS MORTALITY
RATES FROM CANCER HAVE GONE DOWN
VIRTUALLY EVERY RACIAL AND
ETHNIC GROUP WITH THE NOTABLE
EXCEPTION OF AMERICAN INDIANS
AND ALASKA NATIVES. BUT THERE'S
STILL A LONG WAY TO GO TO
ADDRESS THIS MULTI-FACETED
PROBLEM. SECOND POINT WAS WE
MUST BE INCLUSIVE IN OUR
RESEARCH AND ALSO IN THE CANCER
RESEARCH WORK FORCE. THIRD, WE
ALL POTENTIALLY HAVE A ROLE TO
PLAY WHETHER FOCUSED ON THE
UNITED STATES OR LOW AND MIDDLE
INCOME COUNTRIES WHICH ALSO HAVE
ENORMOUS CANCER DISPARITIES. OUR
RULES CAN SPAN A WIDE RANGE OF
RESEARCH FROM TECHNOLOGY
DEVELOPMENT AIMED AT REDUCING
DISPARITIES TO RESEARCH ITSELF
ON THE AFFECTED POPULATIONS.
NEXT SLIDE. I NOW AM GOING TO
TALK ABOUT THE CANCER MOON SHOT
AND AS PRESIDENT BIDEN HAS SAID,
ENDING CANCER FOR AS WE KNOW IT
FOR ALL. NEXT SLIDE. LAST
SEPTEMBER EXACTLY A MONTH AGO,
THE PRESIDENT ANNOUNCED THAT
BEATING CANCER IS SOMETHING WE
CAN DO TOGETHER AND THAT IS WHY
I'M HERE TODAY, WAS EXACTLY A
MONTH AGO ON THE 60TH
ANNIVERSARY OF PRESIDENT
KENNEDY'S MOON SHOT ADDRESS. HE
TALKED ABOUT A NUMBER OF NCI
INITIATIVES BUT EVEN MORE
IMPORTANT, DURING HIS SPEECH HE
INTRODUCED MONICA WHO WAS IN THE
ODD YENS. AND TALKED ABOUT WE
CAN USHER IN THE SAME
UNWILLINGNESS TO POSTPONE THE
SAME NATIONAL PURPOSE TO END
CANCER AS WE KNOW IT. THREE OF
THE PROGRAMS PRESIDENT BIDEN
MENTIONED WERE CANCER MOON SHOT
SCHOLARS PROGRAM, OUR TELEHEALTH
PROGRAM WHERE WE REASONABLY
GIVEN NUMBER OF AWARDS AND
MULTI-CANCER DETECTION TEST. YOU
CAN FIND OUT MORE ABOUT THESE
AREAS THAT THE NCI WEBSITE UNDER
ABOUT THE CANCER MOON SHOT SHOTE
OF THE REALLY KEY FEATURES AS I
HAVE DISCUSSED PREVIOUSLY IS
INCREASING ENROLLMENT OF
UNDER-REPRESENTED GROUPS TO NCI
CLINICAL TRIALS. THE GOAL IS TO
MIMIC THE AT RISK POPULATION FOR
THE SPECIFIC CANCER STUDY
INCLUDING PEOPLE WITH
MULTICO-MORBIDITIES UP TO NOW
GENERALLY INCLUDED IN THE
CLINICAL TRIALS. WE NEED A
GREATER INVESTMENT FOR
INCREASING COMMUNITY ENGAGEMENT.
WE HAVE SEVERAL PROGRAMS ON
THAT. AS I MENTIONED EARLIER,
MORE DIVERSITY AMONG HEALTHCARE
PROVIDERS. AND NCI IS SUPPORTING
THIS DEVELOPMENT AS WELL. THE
NEXT SLIDE TELLS YOU ABOUT SOME
OF THE PROGRESS THAT WE HAVE
MADE AS A RESULT OF LONG TERM
COMMITMENT THAT IN 2000 ONLY
ABOUT 14% OF THE ENROLLMENT IN
CLINICAL TRIALS WERE AMONG
MINORITIES. WHEREAS AS A RESULT
OF CONCERTED EFFORT BY MCKASKILL
STEVENS AND OTHERS, A CRUEL TO
CLINICAL TRIALS THROUGH NCI
COMMUNITY ONCOLOGY RESEARCH
PROGRAM AND THE NATIONAL
CLINICAL TRIALS NETWORK IT HAS
GONE UP TO 25% IN RECENT THREE
YEAR PERIOD. DURING THE PANDEMIC
THE INCREASE ACTUALLY HAS EVEN
BEEN HIGHER WITH CLOSER TO 30%
ENROLLMENT IN 20 AND 21. NEXT
SLIDE. NEXT MONTH WE ARE
TALKING ABOUT THE IMPORTANCE NOT
JUST OF INCREASING DIVERSITY
EQUITY INCLUSION IN LATE PHASE
TRIALS BUT ALSO EARLY PHASE
TRIALS. . SO NEXT MONTH ON
NOVEMBER 16TH GOING TO BE A
MEETING TO DISCUSS THIS ISSUE
WITH EARLY PHASE TRIALS. ANYONE
WHO WOULD LIKE TO PARTICIPATE IS
GOING TO BE A VIRTUAL MEETING.
PLEASE FEEL FREE TO DO SO. MY
LAST TOPIC IS TO TALK ABOUT THE
ANNUAL PLAN AND BUDGET PROPOSAL
FOR FY 24. WE USUALLY ARE A YEAR
AHEAD OF WHERE THE BUDGET IS.
THE PLAN CAME OUT LAST MONTH AS
WE WERE ENDING FY 22. WE USUALLY
HIGHLIGHT A FEW AREAS, THEY ARE
NOT COMPREHENSIVE, NOT INTENDED
TO BE -- THIS IS WHAT WE ARE --
WHAT WE ARE PRIORITIZING. IT IS
REALLY THIS IS WHAT WE THINK ARE
SOME INTERESTING AREAS TO
DISCUSS. THE NEXT SLIDE SHOWS
YOU THE FOUR AREAS THAT WERE
HIGHLIGHTED, ASYMPTOMATIC
MULTI-CANCER DETECTION, CELL
THERAPY TO TREAT CANCER
PERSISTENT POVERTY AND CANCER.
UNDRUGABLE CANCER TARGETS. WE
BELIEVE AS TIME GOES ON THE
NUMBER OF UNDRUGGABLE CANCER
TARGETS HAVE REALLY DIMINISHED
SUBSTANTIALLY. I THINK DIRECTLY
TARGETING TUMOR SUPPRESSER
PROTEINS, REMAINS A CHALLENGE.
BUT IN MANY OTHER WAYS THE
POSITIVE FACTORS THAT CONTRIBUTE
TO INDUCTION AND MAINTENANCE OF
CANCER REALLY MORE AND MORE OF
THEM ARE COMING UNDER OUR SWAY
IN TERMS OF BEING CANDIDATE
INTERVENTIONS. SOME OF THAT WILL
BE DISCUSSED NEXT WEEK ON THE
FIRST DAY OF THE RAS SYMPOSIUM
BUT AS IT RELATES TO RAS. THIS
TALKS ABOUT THE PROPOSAL FROM
THE NCI FOR INCREASING THE
CANCER BUDGET BETWEEN 2023 AND
2024. I WANT YOU TO THINK ABOUT
THIS AS FIRST INCREASING THE
BASE BUDGET BECAUSE IT IS
ABSOLUTELY CRITICAL, THERE WERE
SO MANY DIFFERENT ASPECTS THAT
ARE SUPPORTED WITH THE BASE
BUDGET. FOR EXAMPLE, THE
FREDERICK NATIONAL LABORATORY
FOR CANCER RESEARCH. THE SPORE
PROGRAMS, THE INVESTIGATOR
INITIATED RESEARCH. THERE'S SO
MANY DIFFERENT AREAS THAT ARE
COVERED BY THE BASE BUDGE BUDGEN
ADDITION, TRYING TO SUPPORT AND
MAKE FEASIBLE THE ASPIRATIONAL
GOALS OF THE BIDEN
ADMINISTRATION TO END CANCER AS
WE KNOW IT FOR ALL. FOR MY LAST
SLIDE, THIS IS A SLIDE THAT I
SHOWED LAST TIME JUST TO REMIND
EVERYONE WE STARTED FY 23, 12
DAYS AGO. WE ARE CURRENTLY IN A
CONTINUING RESOLUTION. WE HOPE
THAT WE MIGHT GET A FULL YEAR
APPROPRIATION BEFORE CHRISTMAS
AS AN EARLY CHRISTMAS GIFT. WE
LOOK FORWARD TO THE
APPROPRIATION ACTUALLY BEING
SUBSTANTIALLY HIGHER THAN EVEN
THE FY 22 APPROPRIATION. THE
SENATE CAME IN WITH THEIR MARK
BEING MORE THAN $400 MILLION.
OVER 2022: THE HOUSE WHICH WAS
A PARTIAL MARK WAS FOR A BIT
UNDER 300 MILLION AND WE NEED TO
SEE WHAT WILL HAPPEN. NCI WILL
MAKE A SUFFICIENT USE OF
RESOURCES AS WE CAN. REGARDLESS
OF WHAT THE FINAL FULL YEAR
APPROPRIATION MAY BE. SO IF I
COULD HAVE THE LAST SLIDE, IT IS
MY PLEASURE TO INTRODUCE DR.
MONICA BERTAGNOLLI. NCI
DIRECTOR, TO SAY A FEW WORDS,
THEN WE WILL TAKE QUESTIONS AND
COMMENTS AFTER MONICA COMPLETES
HER REMARKS.
>>THANK YOU SO MUCH. FIRST
THING FIRST. I DON'T HAVE COVID.
RUN OF THE MILL COLD, WHO KNEW
THOSE THINGS STILL HAPPEN BUT I
HAVE BEEN TESTED FIVE TIMES. I
DON'T HAVE COVID. BUT THE DAYS
WHEN IT WAS ACCEPTABLE TO BE
SNEEZING AND COUGHING A BIT IN A
ROOM WITH YOUR COLLEAGUES ARE
LONG GONE. SO I STAYED HOME. TO
BE POLITE TO EVERYONE. THANK YOU
DOUG FOR YOUR CONSIDERATION. I'M
JUST FINE. SECOND DOUG HIT QUOTE
I HIT THE GROUND RUNNING,
UNQUOTE. LET ME TELL YOU WHY I
WAS ABLE TO HIT THE GROUND WITH
AT LEAST SOME SOLID GROUND UNDER
MY FEET, THAT WAS DUE TO DOUG
AND JIM AND DINA AND ANN. I'M
JUST GIVING YOU THE TOP LIST
HERE WHO WERE SO GENEROUS TO ME
IN THE DAYS THAT I WAS TRYING TO
PREP TO TAKE THE REIGNS. I OWE
THEM A TREMENDOUS AMOUNT HELPING
ME GET UP TO SPEED. THAT'S WHY
I HAVE ANY STABILITY RIGHT NOW,
GRATEFUL TO HAVE THEIR CONTINUED
HELP. THANK YOU TO DOUG FINALLY.
THIS IS THE THIRD TIME HE HAS
TAKEN OVER AND IT HAS BEEN CLEAR
THAT EVERYONE WENT WITHOUT A
HITCH. NCI JUST KEPT MOVING
THROUGH ITS MISSION WITHOUT A
SINGLE LOSS OF FORWARD MOMENTUM
OR STABILITY THROUGH DOUG'S
LEADERSHIP. SO HUE SO MUCH, DOUG
FOR THAT. FIRST OF ALL, I AM
REALLY ONE OF THE THINGS I AM
ALMOST MOST EXCITED FRANKLY,
ABOUT THIS POSITION IS THE
OPPORTUNITY TO WORK WITH
FREDERICK NATIONAL LABS. I AM
FAMILIAR WITH FEDERALLY FUNDED
RESEARCH AND DEVELOPMENT
CENTERS, I HAVE SPENT THE LAST
SEVEN PLUS YEARS WORKING VERY
CLOSELY WITH MIDER CORPORATION
ON THEIR ACTIVITIES, FUNDED BY
HEALTH AND HUMAN SERVICES BY
OTHER PARTS OF HEALTH AND HUMAN
SERVICES AND BY DEPARTMENT OF
DEFENSE. I HAVE BEEN A
COLLABORATOR IN MANY ACTIVITIES.
THE MOST SIGNIFICANT RELATED TO
CANCER INVOLVING THE FDA. SO I'M
VERY FAMILIAR WITH THE FFRDC
MECHANISM AND I'M A HUGE FAN. I
UNDERSTAND CLEARLY IT BRINGS
ESSENTIAL THING TO NCI. THAT IS
INFRASTRUCTURE SUPPORT FOR
INTRAMURAL INVESTIGATORS.
ABSOLUTELY CRUCIAL AND WOULD BE
DIFFICULT TO ACHIEVE IN OTHER
WAYS. ON TOP OF THAT IMPORTANT
SERVICE PROVIDES FLEXIBILITY AND
THE BRING IN EXPERTISE WHEREVER
THAT MIGHT BE. TO UNDERTAKE
SPECIAL PROJECTS THAT HAVE HAVE
VERY HIGHLY DEFINED SCOPE AND
LIMITED DURATION TO ACHIEVE
GOALS THAT THEN CAN BE
DISSEMINATED TO THE ENTIRE WORLD
TO BENEFIT OF THOSE WHO ARE
TACKLING PROBLEMS. THE FFRDC
MECHANISM IS A FLEXIBLE
INCREDIBLY COLLABORATIVE WAY TO
ACHIEVE THAT IS I HAVE FOUND
UNPARALLELED. VERY GRATEFUL FOR
THIS ORGANIZATION. AND
ASSOCIATION WITH NCI AND NIH.
THE FINAL THING TO SAY IS IRAM
HERE TO LISTEN, STILL LEARNING
STILL HAVE A LOT TO LEARN ABOUT
INDIVIDUALLY WHAT FREDERICK
HISTORY IS, WHAT IT IS DOING,
PRIORITIES. MOST IMPORTANT WHICH
IS WHAT WE NEED FROM YOU.
CRITICAL FEEDBACK ON WHAT WE CAN
DO BETTER. DON'T PULL PUNCHES.
WE NEED TO KNOW WHAT ARE
OPPORTUNITIES MISSED, WHAT ARE
-- WHAT HAS GONE WELL, WHAT IS
NOT BEEN GREAT AND WHAT ARE IN
PARTICULAR WHAT ARE
OPPORTUNITIES SO THAT WE USE THE
RESOURCES DEVOTED TO FREDERICK
THE BEST WAY POSSIBLE. THAT IS
IT. I'M HERE TO LEARN AND
GRATEFUL FOR YOUR ADVICE AND
PARTICIPATION IN THIS IMPORTANT
ADVISORY COMMITTEE FOR
FREDERICK. THANKS GUESS WE WILL
TAKE QUESTIONS NOW. ANYONE.
>>I TOO HAVE A COLD AND BEEN
TESTED, WE ARE IN THE SAME
PLACE. WHEN YOU SNEEZE AND COUGH
EVERYONE LOOKS AT YOU AND YOU
HAVE TO SHOW YOUR TEST RESULTS.
IT IS CRAZY. I AM EXCITED FOR
YOUR LEADERSHIP. SURE EVERYONE
IS AWARE SHE IS FIRST NAIL NCI
DIRECTOR WE HAVE HAD,
CONTRIBUTES TO DIVERSITY AND
FOCUS ON THOSE ISSUES. EXCITED
FOR YOUR LEADERSHIP. I THINK YOU
WILL FIND FREDERICK IS I DON'T
WANT TO SAY IT IS A DIAMOND IN
THE ROUGH BECAUSE MANY WAYS IT
IS A INDICTMENT BUT THE
CHALLENGE IS GETTING THE WORD
OUT OUT SO EVERYBODY KNOWS, THE
CAPABILITIES AND WHAT FREDERICK
CAN DO FOR THEM OR WHAT THINGS
THEY OFFER. PLEASE, WHO ELSE ON
THE COMMITTEE WOULD LIKE TO ASK
A QUESTION OR COMMENT. Z YES.
THERE WE GO.
>>THERE WAS MENTION TRYING TO
EXTEND RANKS OF TARGETS
MANIPULATED, UNDRUGGABLE
TARGETS, IF YOU WILL. I HATE
THAT TERM. BUT JUST THINGS WE
HAVE DRUGGED. WHAT IS THE VISION
HOW TO DO THAT IN PRACTICE TO
ADVANCE THAT MISSION? POSSIBLE
DA, I'LL START AND MAYBE JIM
DOROSHOW WOULD LIKE TO COMMENT
AS WELL. ONE OF THE PROPOSALS
WE HAVE MADE FOR THE CANCER MOON
SHOT TO INCREASE PIPELINE OF NEW
DRUGS. WE SEE OCCURRING IN AT
LEAST TWO DIFFERENT WAYS, ONE IS
THROUGH ONE THROUGH THE NEXT
PROGRAM DISCUSSED HERE AND IS
RUN THROUGH THE FREDERICK
NATIONAL LAB BUT THE OTHER CAN
BE THROUGH INVESTIGATOR
INITIATED RESEARCH OF OTHER
KINDS JIM, DO YOU WANT TO
COMMENT?
>>YOU WHERE MUTED.
>>IF I CAN UNMUTE. OKAY. IT
IS A GREAT QUESTION. I WANT TO
REITERATE WHAT DOUG SAID BECAUSE
ONE OF THE THINGS WE FIND IS
THAT THOUGH WE GET LOTS OF
APPLICATIONS WE WOULD LIKE MANY
MORE APPLICATIONS FOR THE NEXT
PROGRAM, WE HAVE A GREAT TEAM
THAT HAS JUST BEEN REVIEWED,
PRODUCTIVITY THE LAST FIVE SIX
YEARS IS GREAT. WE HAVE A VERY
OUTSTANDING WAY TO SUPPORT
OUTSTANDING INVESTIGATORS.
ESPECIALLY THE TRANSITION FROM
RO1 SPONSORED RESEARCH WHICH
NEEDS TO INCREASE BUT THEN TO
KINDS OF THINGS HARD TO DO AT
UNIVERSITY. TO MAKE THOSE
FACILITIES AND RESOURCES
AVAILABLE TO INVESTIGATORS SO
THEY CAN MOVE ON TO THE
COMMERCIAL SPHERE. WE HAVE A
GENEROUS BUDGET BUT NOT ENOUGH
TO SUPPORT THE RANGE OF PROJECTS
THAT WE LIKE TO MOVE FORWARD. SO
WE ARE HOPEFUL THAT THOSE
RESOURCES WOULD BE FORTHCOMING
IF THE MOON SHOT IS FUNDED.
>>BEFORE MONICA SAYS WHAT SHE
THINKS, IT IS NOT AT ALL THAT WE
THINK ABOUT WORKING
INDEPENDENTLY OF BIOTECH AND
PHARMACEUTICAL INDUSTRY BUT THAT
IT HAS BEEN DEMONSTRATED OVER
THE LAST FEW YEARS, THAT
INVESTIGATORS HAVE AN IMPORTANT
ROLE TO PLAY WHEN IT COMES TO
TRANSLATIONAL RESEARCH. MONICA.
>>I GUESS THE ONLY COMMENT TO
THROW HERE ONE OF THE THINGS NCI
CORE TO EVERYTHING NCI DOES IS
ROBUST BASIC SCIENCE INITIATIVE
THAT IS FOCUSED ON DEVELOPING
CLINICAL TREATMENTS AND
PREVENTION APPROACH. WHEN YOU
SAY UNDRUGGABLE, WHAT DOES THAT
MEAN? WE NEED TO DOUBLE DOWN ON
CORE ACTIVITY IS UNDERSTANDING
WHAT CANCER MEANS. UNDERSTANDING
DIVERSITY ACROSS POPULATIONS AND
WAYS TO CIRCUMVENT THAT, THAT'S
BETTER THAN SAYING SOMETHING IS
UNDRUGGABLE BUT IT IS A BUZZ
WORD THAT WE HAVE TO SOMEHOW
DEAL WITH, SO I THINK WITHIN
THIS PART OF THE MOON SHOT, IT
WILL BE A WAY OF EXPRESSING
SIGNALING VERY CLEARLY, THAT YOU
CAN'T EVER GIVE UP ON BASIC
DISCOVERY RESEARCH TO UNDERSTAND
BIOLOGY AND ACHIEVE THERAPEU
THERAPEUTICS.
>>TOTALLY AGREE. I WOULD JUST
SAY THERE IS CERTAINLY A BIAS
AGAINST NON-TRADITIONAL TARGETS
IN PHARMA MAKES SENSE BECAUSE
THEY ARE LOOKING TO GET TO A
DRUG QUICKLY. I THINK ACADEMIC
RESEARCH HAS A VERY IMPORTANT
ROLE TO PLAY IN EXPANDING THE
UNIVERSE OF TARGETS, TIPPET OF
TARGETS HOW TO TARGET, BUT THAT
REQUIRES REVIEWERS AND GRANT
MECHANISMS THAT WILL GO OUT ON A
LIMB TO TAKE THE RISK TO SEE HOW
CAN WE TARGET SOMETHING NOVEL
THAT HASN'T BEEN TARGETED
PREVIOUSLY.
>>WE HAVE A BUNCH OF QUESTIONS,
START WITH DANIEL. YOU ARE
MUTED.
>>CAN YOU HEAR ME NOW?
>>YES.
>>ONCOLOGIST, I SPECIALIZE IN
OVARIAN CANCER AND I'M DELIGHTED
THAT MONICA AS A SURGEON SIGN
TICES YOU HAVE AN INCREDIBLE
CAREER, MY CONCERNS ARE TWOFOLD,
ONE THE LACK OF DIMINISHING ROLE
OF THE SURGEON SCIENTIST.
WONDERING IF THERE IS ANYTHING
RELATED SPECIFICALLY TO THAT
GROUP OF PEOPLE WHO PLAY A VERY
UNIQUE ROLE IN TRANSLATING
REALLY FUNDAMENTAL BASIC
FINDINGS TO THE CLINIC IS MY
FIRST QUESTION. SECOND QUESTION
HAS TO DO WITH DIVERSITY.
>>SURGEON SCIENTIST, IT IS
CLEAR WHAT THE ISSUE IS THERE, I
WILL JUST SAY IT. SURGEONS MAKE
-- ARE MUCH, MUCH MORE EFFECTIVE
WITHIN THEIR ACADEMIC
INSTITUTIONS. WITHIN THE
OPERATING ROOM THAN WHEN IN THE
RESEARCH LABORATORY. WHEN THEY
ARE IN THE OPERATING ROOM THEY
MAKE TEN TIMES THE MONEY, WHEN
THEY ARE IN THE RESEARCH LAB. IT
IS AN ECONOMICKISH SHAH SHOE AND
HAS BEEN FOR THE LAST 40 YEARS.
CERTAINLY MY ENTIRE CAREER. THE
WAY WE GET SURGEON SCIENTISTS
BECAUSE THERE ARE PLENTY THAT
COME OUT OF TRAINING PROGRAMS,
COME OUT WITH Ph.D.s, COME
OUT WITH EXCELLENT CREDENTIALS.
IS TO FIND A WAY TO GET THEM
FUNDED. GET THEM FUNDED BY NIH
GRANTS. BECAUSE THAT IS THE ONLY
THING THAT BUYS THEM THEIR
ABILITY TO DO WORK IN OUR
CURRENT ACADEMIC CENTERS. AND
BUYS THEIR TIME AWAY FRANKLY
FROM BEING IN THE OPERATING ROOM
ALL THE TIME. I THINK ANY
PROGRAMS THAT SUPPORT HIGH
QUALITY INDIVIDUALS TO BE ABLE
TO ACHIEVE THAT FUNDING IS GOING
TO BE THE ONLY WAY TO SOLVE THIS
PROBLEM.
>>THIS IS DOUG. LET ME SAY THAT
ONE OF THE NEW PROGRAMS WE HAVE
IS THE K AWARDS SPECIFICALLY FOR
SURGEONS AND TRAINING WHICH NOW
ARE PERMITTING 50% TIME RATHER
THAN THE 75% AS THE MINIMUM
AMOUNT. THE FIRST CLASS SEEM TO
BE A TERRIFIC GROUP OF PEOPLE
AND LOOKING FORWARD TO ANOTHER
CLASS IN THE COMING YEAR. I WAS
TALKING YESTERDAY WITH MARTHA
ZEIGLER FROM THE INTRAMURAL
PROGRAM WHO IS A SURGEON AND
SHE'S DOING SOME ANALYSES OF
SURGEONS AND ONE OF THE THINGS
SHE POINTED OUT IS IN THE RECENT
PAST OF THE SURGEONS WHO HAVE
RO1 AWARDS FROM NCI, THREE
QUARTERS OF THEM ARE FOR BASIC
RESEARCH, GETTING BACK TO THE
ISSUE MONICA YOU WERE TALKING
ABOUT BUT THE OVERALL PROPORTION
OF SURGEONS INVOLVED IN GETTING
NCI AWARDS HAS GONE UP A BIT
OVER THE LAST FEW YEARS. IN
CONTRAST TO PHYSICIAN SCIENTISTS
IN GENERAL.
>>IF I CAN MAKE ONE COMMENT,
THIS WAS AMONG CANCER CENTER
DIRECTORS, NOT PERTINENT TO
FREDERICK BUT THE CANCER CENTERS
BRANCH AND NCI DESIGNATION IS
THAT IF PROTECTED TIME COULD BE
PART OF INSTITUTIONAL
COMMITMENTS SUCH THAT
INSTITUTIONS WOULD HELP TO
SUPPORT PROTECTED TIME. IN
CANCER CENTERS GET CREDIT FOR
THAT, THAT MIGHT INCENTIVIZE A
LITTLE BIT MORE PROTECTED TIME.
BECAUSE THERE IS SUCH A
FINANCIAL CRUNCH THESE
INSTITUTIONS HAVE.
>>I CAN TO MAKE A PLUG RELATED
TO DIVERSITY AND HEALTH
DISPARITIES THAT THE GREATEST
DISPARITY SIGN IN GAIN LO
DODGECAL CANCER IS AMONG BLACK
WOMEN DIAGNOSED WITH ENDOMETRIAL
CANCER. AND THE INCIDENCE IS
RISING A RAPIDLY. THE MORTALITY
IS ALSO ASTOUNDING. I HOPE THAT
WE CAN FIND WAYS TO BRIDGE OUR
BASIC FINDINGS AGGRESSIVE
MOLECULAR TYPES WITH WHAT WE ARE
SEEING CLINICALLY
>>I PRESENTED SOMETHING ABOUT
THE NON-ENDOMETRIAL CANCER LAST
TIME WHERE THE STATISTICS ARE
JUST STAGGERING FOR MORTALITY
RATE ESPECIALLY AMONG AFRICAN
AMERICAN WOMEN, BUT NOW ALSO
AMONG HISPANIC WOMEN. WE ARE
PLANNING TO HAVE A WORKSHOP IN
THE FIRST QUARTER OF NEXT YEAR.
TO DEAL WITH THIS. THIS ALREADY
WAS A MOON SHOT ACTIVITY FROM
MOON SHOT 1.0. BUT IT IS CLEAR
WE NEED TO PUT MORE EFFORT INTO
THIS AREA.
>>SO WE HAVE FOUR MINUTES LEFT.
ALRY SOB?
>>COUPLE OF THINGS. I IT IS T
A DIAMOND IN THE ROUGH BUT A
HIDDEN DIAMOND. DR. JOHNSON AND
I TALKED HOW THE ADVISORY BOARD
CAN HELP ELEVATE OR DEVELOP
STRATEGY OR TACTICAL PLANS THAT
WILL HELP THAT HIDDEN DIAMOND
BECOME A VISIBLE DIAMOND. THE
SECOND THING IS I WAS INTRIGUED
THAT ONE OF THE BUDGETS
PRIORITIES WAS CELL THERAPY FOR
TREATMENT OF CANCER. THAT IS MY
JAM. I WANTED TO KNOW WHERE I
COULD FIND OUT MORE DETAILS ON
THAT.
>>LET JIM DOROSHOW RESPOND TO
THAT
>>MY APOLOGIES IN MY OFFICE
BUILDING 31. DOING CONSTRUCTION
BOTH ABOVE AND BELOW ME SO I
MISSED PART OF THE FIRST PART OF
YOUR QUESTION BECAUSE SOME
INCREDIBLE NOISE I HAVE NO IDEA
WHAT IT WAS, I HOPE THE ROOF --
CEILING IS OKAY. CAN I ASK YOU
REPEAT THE FIRST PART OF YOUR
QUESTION?
>>THE ONLY THING RELEVANT TO
YOU IS IN ONE OF THE BUDGET
PRIORITIES FOR UPCOMING FISCAL
YEAR WAS CELL THERAPY FOR
TREATMENT OF CANCER. INTO FIND
OUT WHERE I COULD GET MORE
INFORMATION ON THAT INITIATIVE
AND WHAT IT INVOLVES.
>>THE FIRST PART IS A NEW RFA
THAT WAS RECENTLY RELEASED.
CALLED CAN CAN ACT. TO SET UP A
NETWORK OF CELL THERAPY CENTERS
THAT WILL DO BOTH PILOT STUDIES,
AT THEIR OWN INSTITUTION BUT IT
IS INTIMATELY CONNECTED WITH OUR
RECENTLY EXPANDED LABS IN
FREDERICK. GMP PRODUCTION
FACILITIES SO THE IDEA IS THAT
PILOT STUDIES DONE SINGLE
INSTITUTION BUT WHEN THERE IS
REQUIREMENT FOR LARGER STUDIES
MULTI-INSTITUTIONAL TRIALS, WILL
PRODUCE THE GMP QUALITY MATERIAL
IN FREDERICK. THEN DO ALL THE
REGULATORY FOR THOSE STUDIES,
HOLD INDs AND HELP
INSTITUTIONS WORK TOGETHER FOR
MULTI-INSTITUTIONAL CELL THERAPY
TRIALS.
>>THANK YOU SO MUCH, JIM. I
WILL KEEP MY PIES OUT FOR THAT
RFA.
>>DO YOU HAVE A QUESTION?
>>DR. MADABHUSHI EMORY
UNIVERSITY. CONGRATULATIONS FOR
MONICA. MY GROUP FOCUS ON
ARTIFICIAL INTELLIGENCE AND
USING AI FROM IMAGING DATA TO
PREDICT TREATMENT RESPONSE I
HAVE BEEN AT A NUMBER OF NCI
WORKSHOPS AND MEETINGS AND I
THINK DOUG WAS AT A MEETING AS
WELL, FOCUSING ON AI AND CANCER
DISPARITIES. DONNA SINGER AND I
WERE AT A MEETING SAN DIEGO THAT
FOCUSED ON AI AND IMMUNOLOGY
THAT HAD A CANCER FOCUS AS WELL
ONE QUESTION THAT KEEPS COMING
UP IS ACCESS TO DATA SETS,
PARTICULARLY COMPLETE HAD
CLINICAL TRIALS. THE IS A
STRUGGLE FOR FOLKS INTERESTED IN
AI AND COMPUTATIONAL ANALYTICS
TO REALLY BE ABLE TO ACCESS DATA
SETS PARTICULARLY SCANS AND
PATHOLOGY IMAGES NOT TISSUE
BLOCKS WHICH IS PATHOLOGY IMAGE
FROM COMPLETED CLINICAL TRIALS,
THAT INCLUDES COOPERATIVE
GROUPS. WHAT STRATEGIES ARE IN
PLACE TO ADDRESS THE ISSUES,
THAT IS HUGE UNTAPPED POTENTIAL
THERE. WHICH SHOULD BE MADE
AVAILABLE.
>>THIS IS AS FAR AS I'M
CONCERNED ONE OF MY HIGHEST
PRIORITIES IS TO FIGURE OUT HOW
WE CAN DO BETTER WITH THIS. AS A
FORMER COOPERATIVE GROUP CHAIR
WHO WOULD FORMAT AND SUBMITTED
EVERY ONE OF OUR LARGE TRIAL TO
ARCHIVE AND PUBLICLY ACCESSIBLE
DATABASES. ALSO SAW ISSUES WITH
BEING ABLE TO STORE AND
INTEGRATE IMAGES TO THOSE
COLLECTIONS SO THEY CAN BE
ADEQUATELY USED BY PEOPLE LIKE
YOU. THIS IS A CRITICAL STEP TO
TAKE. WE HAVE LOTS OF DATA SETS
AND LOTS OF DATA COLLECTED. WE
ARE NOT USING IT OPTIMALLY. VERY
CLEARLY. SO I DON'T HAVE AN
ANSWER FOR YOU RIGHT NOW. I CAN
JUST TELL YOU WHAT YOU HAVE
ARTICULATED I HAVE HEARD FROM SO
MANY DIFFERENT AVENUES WE HAVE
TO SIT DOWN AND FIGURE HOW TO
TAKE THIS ON. I MADE A JOKE I
THINK EARLIER IN THE WEEK WHEN I
SAY WE JUST NEED A MATCH MAKER
YOU WERE WHERE IS DATA WHO NEEDS
IT HOW WE GET IT TO THEM BECAUSE
WE CAN DO BETTER. DON'T HAVE AN
ANSWER YET BUT IT IS HIGH
PRIORITY TO FIGURE OUT WHAT WE
DO.
>>OKAY. NEED TO MOVE ON. DOUG,
I TURN IT BACK OVER TO YOU.
>>WE WANT TO THANK CAT BOLLARD
AND LINCOLN STEIN FOR HAVING
BEEN IMPORTANT AND ACTIVE
MEMBERS OF THE FREDERICK
NATIONAL LABORATORY ADVISORY
COMMITTEE. I HAVE TO WARN BOTH
OF YOU THAT WE KNOW WHERE YOU
LIVE. WE WILL FIND OTHER
APPLICATIONS AND OTHER ENDEAVORS
BECAUSE THE TWO OF YOU ARE MUCH
TOO GOOD TO MAKE THIS ADIEU, SO
THIS IS AN AU REVOIR. THANKS SO
MUCH.
>>THANKS DOUG. IT DOES WORRY ME
BUT THANK YOU.
>>THANK YOU, FOR YOUR SERVICE.
>>SCOTT, YOU ARE MUTED I
BELIEVE.
OPERATOR: I WANT TO
CONGRATULATE. THANK YOU FOR
YOUR SERVICE.
>>GET US BACK ON SCHEDULE. MY
PLEASURE, WE WILL HEAR FROM DR.
DWIGHT NISSLEY TO TALK ABOUT
CRYOEM TRAINING. GOOD MORNING.
>>I LEAD THE CANCER RESEARCH
TECHNOLOGY PROGRAM HERE AT THE
FREDERICK NATIONAL LABORATORY
WHICH INCLUDES THE NATIONAL
CRYOEM FACILITY. I WILL TELL YOU
ABOUT THE TRAINING PROGRAM WE
HELD RECENTLY. SO WE STOOD UP
THE NATIONAL CRYOEM FACILITY IN
2017. WITH THE IDEA OF PROVIDING
A RESOURCE TO THE COMMUNITY, TO
THE NATION TO COLLECT HIGH
QUALITY CRYOEM DATA. WE ALSO
COUPLE OF YEARS AGO SET UP
TECHNOLOGY COMPONENT WHICH IS
MEANT TO EXPLORE NEW APPROACH
AND FEED INTO THE NSEF FOR THE
BENEFIT OF NATIONAL CANCER
RESEARCH COMMUNITY. EARLY ON WE
IDENTIFIED THREE COMMUNITIES WE
THOUGHT WERE IMPORTANT TO TRY TO
SERVE THROUGH THESE EFFORTS.
THE FIRST ONE WAS PEOPLE WITH
EXPERIENCE IN CRYOEM NEED ACCESS
TO HIGH INSTRUMENTATION WHICH
CAN BE EXPENSIVE AND SOME OF THE
EXPERTISE TO RUN IT. THE SECOND
COMMUNITY WE THOUGHT ENGAGE IN
TIME THOSE EXPERIENCE STRUCTURAL
BIOLOGY INCLUDING
CRYSTALLOGRAPHERS NMR PEOPLE,
UNDERSTANDING BIOCHEMISTRY BUT
NEEDED TRAINING OR ACCESS TO
SAMPLE PREPARATION AN DATA
COLLECTION. THE THIRD WE WANTED
TO ENGAGE LONG TERM BIOLOGIST
INTERESTED IN BIOMEDICAL
PROBLEMS THAT BENEFIT FROM A
STRUCTURAL BIOLOGY APPROACH.
PROBABLY NEED MORE INTERACTION
OR TRAINING. THE FIRST COMMUNITY
WE SET UP THE COLLECTION
FACILITY. THIS IS METRICS THIS
IS THE LAST FIEFS YEARS FOR THE
COLLECTION FACILITY, VOIDED
SUPPORT OR COLLECTED DATA FROM
50 INSTITUTION AND NOW MORE THAN
125 INVESTIGATORS. COMING UP ON
900 IMAGING SESSIONS, AND THIS
STARTED TO RESULT IN
PUBLICATIONS WITH CURRENTLY
PROBABLY 30 PUBLICATIONS COMING
OUT PER YEAR THAT ACTINOLEK OUR
COLLECTION -- ACKNOWLEDGE OUR
COLLECTION. THEY BOTH HAVE TIME
K 3 CAMERA DETECTOR. WITH AN
ENERGY FILTER. WE CURRENTLY
COLLECT FOR TWO DAY SESSION TO
GET ABOUT SIX TO 7,000 IMAGES
WHICH IS SUFFICIENT FOR A GOOD
STRUCTURE IF A GOOD SAMPLE, WE
ADDED FRINGE FREE IMAGING WHICH
INCREASES THE AMOUNT OF DATA
THAT CAN BE ACQUIRED DURING
COLLECTION SESSION AND UPDATED
THE WORK FLOW IN SOME OF THE
WARE WE USE TO COLLECT DATA.
MOVERRING TO THE SECOND SET OF
BIOLOGISTS WE THOUGHT WOULD
PROVIDE RESOURCES TO, THOSE
EXPERIENCE WITH BIOCHEMISTRY AND
STRUCTURAL BIOLOGY. PART OF WHAT
WE SET UP NOW, LONG TERM WOULD
LIKE TO ACTUALLY START PROVIDING
THIS AS SERVICE ONCE WE VALIDATE
THIS PLATFORM, AUTOMATED GRID
PREPARATION, MAKING SAMPLES CAN
BE CHALLENGING AND TAKES
PRACTICE IN THE ART. THE SYSTEM
WE REQUIRED AND INVOLVED IS IN
VITROJET. WE HOPE IT GIVES MORE
CONTROL OVER SAMPLES AND
REPRODUCIBILITY, WE ARE
VALIDATING THAT RIGHT NOW AND
EVENTUALLY PROVIDE ACCESS TO
USER TO THIS SAMPLE PREPARATION
APPROACH. IN THE TECHNOLOGY
DEVELOPMENT COMPONENT, WE LOOK
FOR NEWER PLATFORMS MORE
ACCESSIBLE IN TERMS OF COST AND
MIGHT BE APPLICABLE FOR
UNIVERSITIES AND OTHER
INSTITUTIONS THESE INCLUDE THE
CRYOARM 200 THAT WE HAVE HERE.
THESE ARE LOWER ENERGY ELECTRON
MICROSCOPES, PAIRED WITH VARIOUS
CAMERAS. WE ARE TRYING TO PUSH
RESOLUTION LIMITS AND AGAIN IN
LOWER COST PLATFORM AND TAKE ON
CHALLENGING SAMPLES. THE GROUP
MADE PROGRESS IN THESE AREAS.
THE THIRD COMMUNITY WE WANT TO
ENGAGE LONG TERM AND FOCUS OF
TRAINING IS PEOPLE THAT HAVE NO
EXPERIENCE IN CRYOEM AND NEED
TRAINING IN ALLS SECRETARIES OF
THE UP PER WORK FLOW. THE
TRAINING SESSION WE SET UP WAS
MEANT TO TARGET THIS GROUP OR
BRING THIS INTO THE FOLD. WE
HELD THE CRYOEM TRAINING PROGRAM
A MONTH AGO AT THE ATRF IN
FREDERICK. IT WAS A ONE WEEK
PROGRAM MORNING FEATURED LECT
LECTURES AND AFTERNOON FEATURED
HANDS ON PRACTICAL EXPERIENCES
IN THE LABS. YANNA AND THOMAS
EDWARDS WERE THE TECHNICAL
SCIENTIFIC LEADS HERE AT THE
NSEF, DESIGNED AND IMPLEMENTED
THE PROGRAM. THERE WERE PEOPLE
THAT HELPED OUT INCLUDING OUR
CHIEF SCIENCE OFFICER,
PARTNERSHIP DEVELOPMENT OFFICE,
GARY ROBINSON, OFFICE OF
SCIENTIFIC OPERATIONS AND PATTY
MARTINEZ FROM THE CANCER
RESEARCH TECHNOLOGY PROGRAM. WE
DECIDED FOR THE FIRST YEAR TO
KEEP SOMEWHAT LIMITED IN SIZE.
WE WANTED 12 ATTENDEES AT THE
WORKSHOP. WE HAT MORE THAN 60
APPROXIMATE APPLICANTS, THEY
SUBMIT AD CV, A LETTER OF
INTEREST, LETTERS OF
RECOMMENDATIONS, WE FORMED A
TEAM HERE OF BOTH FREDERICK
NATIONAL LAB AND GOVERNMENT
PERSONNEL THAT REVIEWED AND
SELECTED THE APPLICANTS. WE GOT
GOOD GEOGRAPHICAL REPRESENTATION
AND TRIED TO MAKE SURE WE WERE
GETTING PEOPLE THAT MAY NOT HAVE
ACCESS TO SOME OF THE TRAINING
OPPORTUNITIES AVAILABLE ELSE
WHERE ACCESS TO THE RAINING
PROGRAM HERE. WE HAD EIGHT
SPEAKER THE OUTSIDE, SEVERAL
FROM SEVERAL THAT WERE PART OF
THE WEEK LONG TRAINING SESSION.
THIS IS THE AGENDA WE HAD A TALK
FROM CYNTHIA WOULDBURG FROM
HOPKINSMENT TALKED HER USE OF
CRYOEM LOOKING AT NUCLEOSOME,
HISTONE STRUCTURE, REGULATION OF
TRANSCRIPTION. WENT OVER
NEGATIVE STAINING PRECURSOR TO
CRYOEM STUDIES AND THOMAS
EDWARDS TALKED GRID PREPARATION.
IN THE AFTERNOON THERE'S HANDS
ON TRAINING FOR GRID PREPARATION
AND SAMPLE PREP. ON DAY TWO,
LOOK AT USING THESE AUTOMATED
PLATFORMS INCLUDING THE VITROJET
FOR SAMPLE PREPARATION, AGAIN
TRY TO STANDARDIZE AND MAKE
AMPLE PREPARATION MORE
ACCESSIBLE TO PEOPLE NOT QUITE
AS EXPERIENCED. DAY 3 WAS A
COURSE ELECTRON MICROSCOPY. WE
HEARD FROMNALLY, ALUMNUS OF
FREDERICK NATIONAL LAB, ALL THE
PLATFORMS THERMAL ISSUE
PROVIDING RIGHT NOW, MATT
HUTCHINSON TALKED DATA STORA ST.
DAY FOUR TO US CANNED ON THEORY
BEHIND ACQUIRING IMAGES IN
CRYOEM PLATFORMS AND APPROACH
PICKING AND CATEGORIZING THINGS
TO 2D CLASSIFICATION THEN BE
USED FOR MODEL BUILDING. AND
DAY FIVE FEATURED OUTSIDE
SPEAKERS AND EXPERTS ON MODEL
BUILDING. IN THE MORNING IT WAS
LECTURE IN THEORY, IN THE
AFTERNOON IT WAS HAND ON
EXPERIENCE BUILDING MODELS, WITH
SOME OF THE DATA SETS THAT
BEFORE COLLECTED HERE. THIS TOOK
WORK OBVIOUSLY. THOMAS EDWARDS
AND TEAM AT THE COLLECTION
FACILITY, DESIGNED AND
IMPLEMENTED AND SUPPORTED A LOT
OF THE COURSE. AND YANNA AND HER
TEAM WERE INVOLVED IN THE
LECTURES AS PARTS OF THE COURSE
OVERALL, STUDENTS OR ATTENDEES,
THEY APPRECIATED THE COURSE,
THEY FELT THAT THERE WAS HANDS
ON EXPERIENCE AND FELT IT WAS
VALUABLE TO THE FEEDBACK WAS
QUITE POSITIVE. THIS IS A PHOTO
OF THE ATTENDEES. WE LIKE TO
THINK OF THIS AS CAN EXAMPLE HOW
WE USE THE NATIONAL LAB TO
NUCLEATE OR ENABLE RESEARCH
COMMUNITY AND WE LOOK FORWARD TO
DOING THESE TYPE OF COURSES IN
THE FUTURE. WITH THAT I WILL
STOP AND TAKE QUESTIONS YOU
MIGHT HAVE. ANY QUESTIONS?
SOUNDS LIKE A VERY SUCCESSFUL
TRAINING PROGRAM. JOHN.
>>THIS IS GREAT. KUDOS FOR
BRINGING THE TECHNOLOGY UP AND
STARTING TO TRAIN THE COMMUNITY.
THE PATH WITH BOTH NMR AND X-RAY
CRYSTALLOGRAPHY OVER THE YEARS
IS THEY EVOLVE FROM HIGHLY
TECHNICAL TO TOOLS MOST HAD
ACCESS TO. THAT WAS TO SOME
EXTENT FACILITATED BY REGIONAL
CENTERS PROVIDING ACCESS. IS
THERE ANY -- I DON'T KNOW IF
THIS IS THE PURVIEW OF FNLAC BUT
IS THERE ANY VIEW OF A MODEL
LIKE THAT, GOING FORWARD FOR
CRYOEM? THERE IS AN NIH FUND
THROUGH NIGMS AND THREE REGIONAL
CENTERS WITH MANY CRYOEM
MICROSCOPE PLATFORMS THOSE ARE
UP AND RUNNING NOW. THE NCI SET
THIS UP FIVE YEARS AGO WITH A
BIT OF FOCUS ON CANCER RELATED
TOPICS WHERE NIGMS ARE OPEN TO
ALL BIOLOGY. THAT MODEL IS IN
PLACE AND PART OF THE LONG TERM
SOLUTION PROVIDING ACCESS TO THE
ENTIRE COUNTRY.
>>THANK YOU, ROB. RAVI.
>>THANK YOU FOR SHARING THOSE
RESOURCES AND ALSO TRAINING, IT
IS VERY IMPORTANT. I WORK ON
DIFFERENT PROJECTS WITH ACADEMIC
AND TRANSLATE THEIR PRODUCTS SO
PASSIONATE ABOUT HAVING THAT
ACCESS ACADEMIC ENTREPRENEURIAL
TO BE ABLE TO ADDRESS KEY
QUESTIONS THEY MAY BE EXPERT,
NOT EXPERT OF BUT ACCESSIBLE TO
THESE TWO AND HAVING HIGH END
MODEL, HIGHLY IMPORTANT TO DRIVE
INNOVATIONS. THINGS THAT ARE
CHALLENGING TO ANALYZE DRUG
TARGETS CELL THERAPY, MEMBRANE
BOUND MOLECULES. THAT IS THE
DRIVING OF RESOLUTION, THE
DRIVING OF QUALITY OF WORK AND
REPRODUCIBILITY,S OR THAT GLAD
TO SEE THAT PUT TO USE IN
FREDERICK FACILITY. TRAINING TO
MAKE OUTREACH PRODUCTIVE
STRATEGIES. SO THESE ARE
OPPORTUNITIES WE MUST SEE TO
REACH OUT TO THOSE SCIENTISTS
WITH LIMITED RESOURCES HAVING
THE GEOGRAPHIC CONSIDERATIONS
FOR TRAINING IS IDEAL, THAT IS
GOOD, ANYTHING WE CAN DO TO
PROMOTE LET US KNOW. I'M STILL
LEARNING HOW THAT OPERATES. TO
HELP YOU ANY CONNECTIONS WE CAN
DO. DR. LOWY, YOU HAD A
QUESTION?
>>I WANTED TO RESPOND TO JOHN'S
EXCELLENT QUESTION. WHEN HAROLD
VARMUS WAS THE NCI DIRECTOR, HE
ACTUALLY WANTED TO HAVE SOME
NETWORK ORGANIZED BY THE NIH.
BUT THAT EFFORT DIDN'T RESONATE
WITH THE REST OF THE NIH. WHEN I
BECAME ACTING DIRECTOR IN 2015,
ONE QUESTION I ASKED FRANCIS
COLLINS WAS WHAT TO DO ABOUT
THIS ISSUE. HE SAID DOUG, IF I
WANT TO DO CRYOEM SET IT UP AT
FREDERICK. DON'T WAIT FOR THE
REST OF THE NIH TO COME ALONG.
THAT IS WHAT WE DID.
>>VERY GOOD. VERY GOOD FOR
SIGHT. ANYTHING ELSE? WE WILL
LEARN ABOUT PATIENT DERIVED
MODELS REPOSITORY BY DR.S
DOROSHOW AND EVRARD.
>>THANKS, CANDICE AND THANKS,
EVERYONE FOR THE OPPORTUNITY TO
GIVE THIS UPDATE TO THE FNLAC
ABOUT THE WHAT WE CALL THE PDMR.
SOME OF YOU HAVE HEARD ABOUT
THIS FACILITY IN THE PAST. I
THINK YOU WILL FIND SOME NEW
THINGS THAT WE HAVE BEEN DOING
AND IT WILL BE GOOD TO GIVE YOU
A STATUS UPDATE OF A PROJECT
NEAR AND DEAR TO MY HEART AND I
HAVE A CHANCE TO SHARE THIS
PRESENTATION WITH MY CLOSE
COLLEAGUE DR. EVRARD WHO MANAGE
IT IS FA SIT IN FREDERICK FOR
THE NCI. THE OUTLINE IS FIRST
TALK MODEL DEVELOPMENT AND
DISTRIBUTION SO YOU GET A SENSE
OF HOW BIG IS THIS, WHAT IS
AVAILABLE TO THE EXTRAMURAL
COMMUNITY, WHO IS TAKING
ADVANTAGE OF IT. I WILL GIVE
YON VIGNETTE OF MECHANISM OF
ACTION STUDY THAT WE HAVE TAKEN
USING THESE MODELS AND THEN
YVONNE WILL SHARE WITH YOU
RECENT MODELING DATA THAT CAME
OUT OF THE QUESTION HOW BEST DO
YOU REPORT XENOGRAPH TO
THERAPEUTIC DATA? ALL OF YOU IF
YOU HAVE BEEN IN THIS BUSINESS
FOR PERIOD OF TIME UNDERSTAND
THE INCREDIBLE LACK OF STANDA
STANDARDIZATION FOR XENOGRAPHING
THE PRE-CLINICAL CLINICAL IN
XENOGRAPHS SO PDMR IN
CONJUNCTION WITH PDX NET WHICH
IS ORIGINAL MOON SHOT PROJECT
WHICH HAS AFFILIATES PRODUCING
MODELS AND EXPERIMENTS,ING TO
WITH US BROADLY HAVE DONE THIS
PROJECT TO BRING TOGETHER LOTS
OF DATA TO TRY TO UNDERSTAND
DEVELOP A TOOL THAT WILL BE
AVAILABLE TO THE GENERAL
COMMUNITY. HELP STANDARDIZE AND
HELP UNDERSTAND IF YOU HAVE A
TREATMENT DOES IT WORK AND HOW
DO YOU BEST REPORT THOSE DATA.
YVONNE WILL MAKE THAT
PRESENTATION. WHAT IS THE PDMR
AND WHY DID IT START? WE WERE
INTERESTED IN DEVELOPING A
REPOSITORY FOR THESE MODELS TO
HELP ACADEMIC DISCOVERY EFFORTS
AND ALSO TO FACILITATE PUBLIC
PRIVATE PARTNERSHIPS. WE
DEVELOPED ANNOTATED SET OF
PASSAGE MODELS COMPREHENSIVE
MOLECULAR CHARACTERIZATION AND
SIGNIFICANT QUALITY CONTROL. OUR
GOAL TO COMPLIMENT EXISTING PDM
INSTITUTIONS AND FOCUS ON
UNDER-REPRESENTED MODELS RARE
CANCER, AND TO TRY TO PUSH THE
ENVELOPE IN TERMS OF DEVELOPING
MODELS FROM THE APPROPRIATE
UNDERSERVED MINORITIES. BOTTOM
LINE FOR THIS EFFORT WAS TO
PROVIDE MODELS AT MODEST COST SO
NO SINGLE INVESTIGATOR EVEN IF
THAT PERSON HAS ONE R21 GRANT OR
ONE RO1 WILL NOT BE ABLE THE
AFFORD MULTIPLE MODELS TO
FACILITATE EXPERIMENTS AND
PROVIDE ALL ASSOCIATED DATA WITH
MODELS WITH CLINICAL HISTORY
PRIOR TREATMENT, HISTOLOGY,
EXOSOME SEQUENCING RNA
SEQUENCING AND THE SOPs THAT
WERE USED TO PRODUCE THIS DATA
ON A PUBLIC WEBSITE. AND IN
FACT THAT WEBSITE REFERENCED
HERE ONE CAN GET THAT DATA
WITHOUT BUYING ANY OF THE
MODELS. FOR ANY KIND OF
INFORMATION YOU WOULD LIKE TO
REVIEW. SO I WILL TALK ABOUT THE
DISTRIBUTION AND MODEL
DEVELOPMENT FIRST PART OF MY
TALK. HERE GIVES YOU AN IDEA WE
HAVE TAKEN THE LAST SEVERAL
YEARS CLOSE TO 4,000 SPECIMENS.
COLLECTED AT INSTITUTIONS ACROSS
THE UNITED STATES, YOU WILL SEE
A LIST OF THOSE INSTITUTIONS.
AND SPECIAL INDEPENDENT MEDIA.
NEXT DAY IMPLANTATION AND NSG
MICE. OVERALL OUR TAKE RATE FOR
ACCESSIBLE SPECIMENS IS 30% BUT
WHAT YOU CAN SEE IS VARIABILITY
THAT IS CONSISTENT WITH THE
GENERAL -- THIS IS A LARGE
EFFORT IF YOU LOOK ACROSS
INDIVIDUAL PUBLICATIONS THIS IS
CONSISTENT WITH WHAT YOU FIND,
WE HAVE A HIGH TAKE RATE FOR
HEAD AND NECK CANCER, HIGH TAKE
RATE FOR MALIGNANT MELANOMAS. GI
CANCER PANCREAS AND COLON, AS
EVERYONE KNOWS WELL ARE FAIRLY
EASY TO ESTABLISH BUT WHAT IS
PERHAPS LESS WELL APPRECIATED IS
HOW DIFFICULT IT IS TO GET
MODELS FROM NEUROENDOCRINE
TUMORS TO GROW. MOST MODEL IT IS
BREAST CANCER THAT WE HAVE ARE
PATIENTS WITH TRIPLE NEGATIVE
BREAST CANCER. VERY DIFFICULT
UNDERTAKING TO GET HORMONE
RESPONSE TUMORS TO GROW IN SG
MICE. WE CAME TO REALIZATION
LATE. BUT TWO, THREE YEARS AGO,
I CAN'T TELL YOU WHICH I
UNDERSTOOD WHY. IN TERMS OF
COLLECTIONS WE GET FROM CENTERS
ACROSS THE COUNTRY IT IS
REMARKABLE HOW MANY RARE TUMORS
WE GET. THIS GIVES AN IDEA FOR
SARCOMAS LARGE NUMBER OF
SARCOMAS WITH DIFFERENT
HISTOLOGICAL SUB TYPES, THERE IS
A 30% TAKE RATE BUT SOME TUMORS
MUCH HIGHER SO THAT HELPED US IN
THE GOAL O OF DOLLING MODELS WE
CAN USE FOR TESTING FOR RARE
TUMORS. WE HAVE AMERICA CAN
BELIEVE CELL CANCERS LOTS OF
THINGS YOU DON'T SEE AND I
WONDER IS THAT BECAUSE NO ONE AT
THE CENTERS THAT ARE SENDING US
TISSUES STUDIES THOSE THINGS SO
MIGHT AS WELL SEND TO THE NCI. I
DON'T KNOW BUT IT IS USEFUL, WE
HAVE OF 6, 700 AVAILABLE MODELS
15, 20% ARE RARE CANCERS. THIS
IS A -- THE RESULT DATA SHOWING
HERE RESULT A SUGGESTION MADE AT
TIME CUPFUL O YEARS AGO WHEN I
MADE A PRESENTATION TO THE FNLAC
ADVISORY COMMITTEE, AS SOMEONE
RAISED HAND AND SAID ARE YOU
TRYING TO COLLECT MODEL RAD BY
AUTOPSY SPECIMENS? THAT COULD BE
USEFUL TO DEVELOP MODEL PRIMARY
AND MULTIPLE METASTATIC SITES SO
WE UNDERTOOK TO DO THAT AND YOU
WILL SEE WE HAVE ABOUT FOUR
MAJOR NCI DESIGNATED CANCER
CENTERS, TO SEND THOSE
SPECIMENS. THIS IS DATA FROM
THE FIRST 80 PATIENTS WE HAVE
GOTTEN MULTIPLE TAKES FROM
DIFFERENT TUMORS. THERE ARE
MAJOR PROGRAMS TO COLLECT TO
PANCREATIC CANCER AT SEVERAL
CANCER CENTERS. THAT'S BEEN A
SUCCESSFUL ENTERPRISE BUT WE
ALSO HAVE BEEN SUCCESSFUL WITH
MELANOMAS AND OTHER TUMORS ALSO
NOT A SURPRISE FOR THOSE WHO
WORK IN MALIGNANCIES HOW
DIFFICULT IT IS TO GROW PROSTATE
CANCER. EVEN FROM METASTATIC
SITES. THAT IS OUR EXPERIENCE AS
WELL. THIS IS A USEFUL
ENTERPRISE BECAUSE WE HAVE
NUMEROUS PATIENTS AVAILABLE
MODELS AVAILABLE TO PATIENTS, WE
HAVE PRIMARY MULTIPLE METASTATIC
SITES, MODEL THOSE MOLECULARLY
CHARACTERIZED AVAILABLE TO
PUBLIC FOR FURTHER EVALUATION. I
TALK ABOUT TRYING TO DEAL WITH
ISSUES WITH MODELS FROM A
DIVERSE POPULATION. ON THE LEFT
YOU CAN SEE THE PATIENT REPORTED
ETHNICITY, IT IS NOT A SURPRISE
MAJORITY OF PATIENTS REPORT
THEMSELVES AS EITHER BEING WHITE
OR UNREPORTED. ABOUT FIVE OR SIX
PERCENT AFRICAN AMERICAN.
ON THE RIGHT FROM SAME NUMBER OF
MODELS THE INFERRED GENETIC
ANCESTRY FROM THE WHOLE EXOME
SEQUENCING WHICH MOST OF THE
PATIENTS ARE EUROPEAN, ABOUT
FIVE OR SIX PERCENT AFRICAN
AMERICAN. THIS IS AN ISSUE WE
BECAME AWARE OF SEVERAL YEARS
AGO, WE HAD TWO FUNDED SITES THE
JOB IS TO EXPAND THE AREA OF
DEVELOPING MORE HISPANIC MODELS,
MODELS FROM PATIENTS OF WIDE
VARIETY OF BACKGROUNDS TO HAVE
THESE THINGS AVAILABLE FOR
SPECIFIC STUDIES APPROPRIATE FOR
THESE PARTICULAR BACKGROUNDS. I
DIDN'T SAY I HAD THE IMAGE WITH
UPPER RIGHT BEGINNING SLIDE, WE
DO SOMETHING PERHAPS THAT IS A
LITTLE DIFFERENT FROM MOST MAYBE
NOT ALL BUT MANY REPOSITORIES OF
THIS TYPE. WE ATTEMPT TO
GENERATE FROM EVERY HUMAN
SURGICAL OR BIOPSY SAMPLE, NOT
ONLY A PDX MODEL BUT AN
ORGANOID, TWO DIMENSIONAL MODEL
EARLY PASSAGE AND CANCER
ASSOCIATED FIBROBLASTS FROM THAT
BIOPSY SURGICAL SPECIMEN. OUR
GOAL IS TO PROVIDE ALL THESE
THINGS MOLECULARLY CHARACTERIZED
FOR INDIVIDUAL WHOSE WANT TO
STUDY IN 2D ORGANOIDS BUT TWO
MORE EXPENSIVE PDX MODEL SYSTEM
WHEN THEY HAVE INITIAL DATA THAT
WILL HELP IN DRUG DEVELOPMENT OR
OTHER BIOLOGICAL ISSUES. WHAT
YOU SEE IN THE CHECK BOARD
BOTTOM FROM ABOUT 169, 170
MODELS, WE HAVE PATIENTS, PDX
PDC FOR 40 PATIENTS, ALL HOSE
THINGS AVAILABLE, A MIX AN MATCH
OF VARIETY OF OTHERS SO MANY
MODELS TO CHOOSE FROM LOTS OF
HISTOLOGIES ONE CAN START IN TWO
DIMENSIONS AND WORK YOUR WAY UP
TO A THREE DIMENSIONAL MODEL AND
PUT IN AND EVALUATE AUTOLOGOUS
CANCER ASSOCIATED FIBROBLAST
TOGETHER FROM THE SAME PATIENT
WHICH IS MOLECULARLY
CHARACTERIZED TO UNDERSTAND THE
INTERACTIONS THAT ARE POSSIBLE.
THE REQUEST RATE LAST SEVERAL
MONTHS HAS GONE UP
SIGNIFICANTLY. NEXT SLIDE. SO
THIS IS A DISTRIBUTION,
SOMEWHERE ORDER OF 2500 MODELS
BUT IT IS BASICALLY EVERYTHING
THAT PEOPLE ASK FOR PDX
FRAGMENTS BUT ALSO FLASH FROZEN
SAMPLES FOR PROTEIN ANALYSIS.
DNA, RNA, AND ORGANOIDS AND
PBCs. ON THE RIGHT YOU CAN SEE
THE DISTRIBUTION OF HISTOLOGIES,
IT IS NOT JUST COLON CANCER BUT
WIDE VARIETY OF MODELS SURPRISED
ME, THERE ARE CERTAIN THINGS YOU
MIGHT OR MIGHT NOT GUESS BUT WE
HAVE HAD SPECIFIC REQUESTS FOR
RENAL CANCER MODELS THAT ARE
HARD TO DEVELOP FAIRLY LARGE
RENAL CANCER AND ORGANOIDS
USEFUL TO NUMEROUS INVESTIGATORS
ACROSS THE COUNTRY. I DIDN'T
WANT TO STOP WITHOUT CALLING OUT
SEVERAL THINGS. JUST GIVES YOU A
LIST OF THE SITES AND
INVESTIGATORS AT THOSE SITES WHO
REQUESTED MODELS ALMOST ALL
DESIGNATED CANCER CENTERS,
INVESTIGATORS THOSE SITES
REQUESTED MODELS. THERE ARE
MULTIPLE INVESTIGATORS WHO
REQUESTED MULTIPLE MODELS SO
THIS IS HEARTENING. USEFUL FOR
CENTERS THAT DON'T HAVE CAPACITY
TO REPOSITORY LIKE THIS OR DON'T
WANT TO INVEST MONEY PEOPLE CAN
REQUEST THESE MODELS FROM US AND
GET THEM AT LOW COST. YOU CAN
SEE VARIETY OF BIOTECHS ACTIVE
IN REQUESTING MODELS BUT ALSO
SOMETHING HEARTENING, ABOUT A
YEAR AGO WE GET A REQUEST FROM
GSK, THEY HAD STARTED THEIR OWN
REPOSITORY TESTING MANY YEARS
AGO AND GAVE UP ON IT AND
DECIDED TO GET BACK --
>>WE LOST YOU.
>>JIM, YOU ARE MUTED.
>>MAYBE THAT CONSTRUCTION
FINALLY TOOK DOWN HIS --
>>MY APOLOGIES. I WILL START
OVER AND TELL YOU THAT WE WERE
HEARTENED THAT GSK BASICALLY
WENT THROUGH OUR CATALOG AND
REDUCESSED LARGE -- REQUESTED
LARGE NUMBER OF MODELS USING
PDXs FOR DRUG SCREENING. WE
HAD LOTS OF REQUESTS FROM
INTRAMURAL INVESTIGATORS BUT
ALSO NCATS AND DOE. NEXT SLIDE
TO CLOSE OUT THIS PART OF MY
TALK, I WANT TO GET MY REAL
APPRECIATION TO LARGE NUMBER OF
NOT ONLY NCI DESIGNATED CANCER
CENTERS BUT MANY OF THE NCOR
SITES ACROSS THE COUNTRY ACTIVE
IN PARTICIPATING AND PROVIDING
US WITH MODELS THAT OTHERWISE WE
NEVER WOULD HAVE BEEN ABLE TO
COLLECT. SO I WILL MOVE TO A ONE
VIGNETTE IN TERMS OF COMPETITIVE
-- COMBINATION TRIAL STUDIES'
THAT MAYBE OF INTEREST. THIS WAS
A PAPER FIVE YEARS AGO MADE
POSSIBLE BECAUSE OF PRECISION
MEDICINE ACTIVITIES THAT WERE
SUPPORTED SOME YEARS AGO, THAT
ALLOWED US AD FREDERICK TO DO A
STUDY THAT TOOK EVERY AVAILABLE
FDA APPROVED THERAPEUTIC AGENT,
AND LOOK AT 5,000 UNIQUE ALL
POSSIBLE COMBINATIONS ACROSS THE
NCI 60 CELL LINE TO TRY TO FIND
UNIQUE COMBINATIONS THAT WOULD
NOT HAVE BEEN PREDICTIVE.
SO THIS IS A SYSTEMATIC STUDY
AND THERE WERE MANY, MANY
COMBINATIONS THAT WOULDN'T HAVE
BEEN PREDICTED. COMBINATION OF
MALOTNIB AND PACK LA TACK SOL.
EVERYTHING ABOVE THE LINE SHOWS
BY BLISS SCORE, MANY, MANY CELL
LINES, NOT JUST HEMATOPOIETIC
CELL LINES WHICH COMBINATION IS
ACTIVE. AND RIPPLE NEGATIVE
BREAST CANCER SHOWN LOWER LEFT
PRODUCES CURES. SO NEXT SLIDE.
WE WERE INTERESTED TO TRY TO
BEGIN TO UNDERSTAND WHY THAT WAS
THE CASE, TURNS OUT THAT LOOKING
CARPALIA CROSS THE CASCADE IT IS
CLEAR APOPTOSIS WAS NOT
MECHANISM OF ACTION FOR THE THIS
COMBINATION. IT IS KNOWN TO
ALTER P GLYCO PROTEIN AND DRUG
EFFLUX SINCE PACLA TOXOL IS A
SUBSTRATE, WE THOUGHT THAT WOULD
BE THE IS DA, IT IS NOT IN VIVO
LOWER LEFT. YOU CAN SEE UPTAKE
IN DEFLUX OF TAXOL IN THIS 468
BREAST CANCER IS NOT AFFECTED BY
NALOTNIB SO WE HAD NO CLEAR
UNDERSTANDING OF WHAT THE
MECHANISM OF ACTION WAS. SO WE
SAID OKAY IS THIS SOMETHING THAT
OCCURS IN XENOGRAPH OR PDX
MODEL?
SO THIS GIVES AN EXAMPLE, WE
WERE ABLE TO STUDY 9 PDX MODELS
AND WHAT IS REMARKABLE ABOUT
WHAT YOU SEE ON THE RIGHT IS A
LOT OF BLUE. THIS IS LOOKING AT
THESE MODELS BY QUALITATIVE
EVALUATION, COMPLETE RESPONSE,
PARTIAL RESPONSE, EFS, TIME
QUADRUPLING, IT IS AN EVENT FREE
SURVIVAL SO TIME TO GROWTH GIVES
YOU AND IN ESSENCE A PSEUDONYM
FOR PFS. UNDER AFC OR WHETHER
ACTUAL TIME PROGRESSIONS WERE
MEASURABLE AND THIS IS A VERY
ACTIVE COMBINATION ACROSS A LOT
OF DIFFERENT MODELS. IT IS
SOMETHING WE COULDN'T HAVE DONE
WITHOUT HAVING THIS REPOSITORY
AVAILABLE. SO THEN THE NEXT
THING IS ONE HAS TO DECONVOLUTE
THAT DATA THAT IS DATA FOR
COMBINATIONS SO THESE DATA WHICH
IS VERY CLEAR AND LEFT SIDE OF
THE SLIDE THAT THESE ARE -- THIS
IS A COMBINATION EFFECT. ACROSS
A VARIETY OF DIFFERENT TUMOR
TYPES. THE BLUE IS FOR
COMBINATION, BROWN IS
PROGRESSIVE DISEASE. YOU SEE
PARTIAL RESPONSE. SO THIS WAS
VERY HEARTENING. AND BECAUSE OF
THE WIDE RANGE OF ACTIVITY
COCOMBO IS NOW TAKEN UP INTO THE
INITIAL NINE ARMS OF THE INITIAL
COME BEMATCH TRIAL. HOW DOES
THIS WORK? WE HAVE DONE MULTIPLE
STUDIES INCLUDING RNA SEQ DATA.
WHAT YOU SEE IS COMBINATION IN
VIVO FOR PDX MODEL AND STANDARD
XENOGRAPH BOTTOM SEEMS TO BE
SIGNIFICANT INCREASE IN SIGHT
COIN PRODUCTION IN TUMORS FROM
THIS COMBINATION THAT IS OFTEN A
COMBINATION SPECIFIC EFFECT THAT
DOESN'T OCCUR TO THAT DEGREE ONE
DRUG OR ANOTHER. WE FOUND
FURTHER ANALYSIS OF RNA SEQ DATA
SHOWS THIS COMBINATION
DRAMATICALLY INCREASES THE
EXPRESSION OF THE GENES INVOLVED
IN RNA AND DNA SIGNALING WHICH
GIVES SOME REASON TO UNDERSTAND
AND EXPECT THAT IT IS REALLY
IMMUNE RESPONSE AT LEAST THE
ACTIVATION CYTOKINE ACTIVATION
SOMETHING THAT MAYBE IMPORTANT.
SO WE ARE ACTIVELY TRYING TO
UNDERSTAND WHETHER OR NOT DNA
SENSING IS -- SETS OFF NECROSIS
OR PERIOPTOTIC CASCADE TO GET A
BETTER UNDERSTANDING OF THIS
MECHANISM OF ACTION. AN EXAMPLE
OF POWER OF HAVING THESE MODELS
AVAILABLE AND DOING SCREENING
AND MECHANISM STUDIES THAT HE
ARE USEFUL AND CAN BE TAKEN INTO
CLINIC. NOW I WOULD LIKE TO
INTRODUCE MY COLLEAGUE, YVONNE
EVRARD WHO OVERSEE IT IS ENTIRE
REPOSITORY TO HELP YOU
UNDERSTAND VERY IMPORTANT
ACTIVITIES P PDMRs ARE
UNDERGOING WITH PDX COLLEAGUES
TO TRY TO STANER ADVERTISE
REPORTING OF PRE-CLINICAL TUMOR
VOLUME RESPONSES. YVONNE.
>>INC. THAT, JIM. SO SOME I
WILL GIVE YOU OVERVIEW OF ONE WE
ARE CURRENTLY DOING IN PDX
DEVELOPMENT TRIAL RESEARCH
NETWORK. PDX FOR SHORT AS WE
MENTIONED CANCER MOON SHOT
PROGRAM IN 2017. THIS GROUP IS
-- WE HAVE A DATA COMMONS
COORDINATING CENTER KEY TO
KEEPING THIS PROJECT PROGRAM
MOVING FORWARD. WE HAVE SIX
PARTICIPATING PDX DEVELOPMENT
AND TRIALS CENTERS, AND THESE
ARE GROUPS THAT DO ALL THE IN
VIVO TRANSLATIONAL RESEARCH AS
WELL AS CREATING MODELSS. A KEY
HERE IS PDX INVOLVED WITH
DIVISION OF CANCER TREATMENT AND
DIAGNOSIS AS WELL AS CENTER TO
REDUCE CANCER HEALTH DISPARITIES
SO TWO ARE FOCUSED ON
TRANSLATIONAL QUESTIONS
INVOLVING RACIAL ETHNIC
MINORITIES. AS A GROUP WE
UNDERGO DIFFERENT ACTIVITIES AND
ONE OF THOSE I WILL TALK ABOUT
TODAY IS INITIATIVE TO LOOK AT
TUMOR VOLUME RESPONSE. SO GO TO
THE NEXT SLIDE, THIS EFFORT WAS
SPEARHEADED BY MD ANDERSON AND
DR. JEFF MOSCOW AT NCI FOR THIS
EFFORT.
THE GOAL HERE WAS TO ASSESS WITH
THE CURRENT NEWS BY THE
COMMUNITY IN PUBLICATIONS AS
WELL AS BY PDX INVESTIGATORS AND
TRY TO SEE IF WE CAN'T DO
SOMETHING BETTER. IT IS
CHALLENGES THERE IS NOT A
STANDARD APPROACH IN VIVO TUMOR
GROWTH ASSESSMENT ACROSS THE
DIFFERENT PUBLICATIONS.
RESPONSES SEEN BY DIFFERENT
GROUPS. WHAT HAS COME OF THIS AS
COLLABORATIVE EFFORT WITH
VARIOUS PDX NET DEVELOPMENT AND
CENTERS IS PDX VOLUME METRIC
ANALYZER. SO DR. BERNSTEIN IS
WORK ON MANUSCRIPT ABOUT TO BE
PUBLISHED IN COMBINATION WITH
THAT SUITE OF TOOLS AVAILABLE
FOR COMMUNITY USE. THE VALUE OF
IMAGE ON BOTTOM TO UPLOAD DATA
AND DO VARIETY OF DIFFERENT
WAYS, VISUALLY REPRESENT THE
DATA AS WELL AS DO STATISTICAL
ANALYSIS. A COUPLE OF EXAMPLES
OF THIS, USING PACLA TAXOL
STUDIES DR. DOROSHOW DISCUSSED
TO SHOW YOU HOW TO USE THIS
METRIC AND KEY RECOMMENDATIONS
OUT OF THIS MAN JEW CRYPT THAT
CAME FROM THE PDX NET COMMUNITY.
YOU THINK IS REALLY IMPORTANT TO
START MOVING TOWARDS
STANDARDIZATION OF REPORTING
ACTIVITY IN PRE-CLINICAL
STUDIES. THIS IS AN EXAMPLE,
MULTIPLE WAYS IN SUITE OF TOOLS
TO GRAPHICALLY REPRESENT THEIR
DATA AND AN EXAMPLE ON THE LEFT,
THOSE THAT WORK WITH PDX WHICH
IS PRESENT VOLUME CHANGE. IT IS
STANDARD WAY TO REPRESENT THE
DATA, MANY WAYS TO DO THIS. THE
STUDY IN THE PACLO TAXOL DATA
RESPONSIVE TO THE COMBINATION.
WILL IS SIMILAR ACTIVITY WITH
PACLA TAXOL IN BLUE, NALOTNIB IS
-- IN THE CONTROL, YOU CAN SEE
ON THE LEFT, IS SHOWING THE
RESPONSE ON THE LEFT. ON THE
RIGHT IS METRIC THAT DR. MOSCOW
PROPOSED TO MOVE INTO LOOKING AT
THESE GRAPHICAL REPRESENTATIONS
IN A DIFFERENT WAY. THAT IS IF
YOU LOOK ON THE LEFT WITH THE
LIMITATION THERE, THE AREA WE
ARE MOST INTERESTED IN IS BOTTOM
TEN PERCENT OF THAT GROUF. SO
HOW DO WE REPRESENT THAT SO WE
CAN SEE WHAT IS HAPPENING WHEN
TUMOR, WHEN AGENTS HAVE
ACTIVITY. SO WE HAVE CREATED THE
SCALED AVERAGE CHANGE
REPRESENTATION, OF THESE GRAPHS
AS A WAY OF GRAPHING THE DATA SO
YOU CAN SEE PLUS AND MINUS 100%.
OR YOU LIMIT THRESHOLD THE UPPER
LEVEL, TO PRE-DEFINED END POINT,
THOSE ARE DETERMINED WITHIN THE
TOOL BY THE INVESTIGATOR
UPLOADING YOUR DATA SO WILL IS
FLEXIBILITY FOR THE INVESTIGATOR
TO DO THIS. YOU CAN SEE VERY
CLEARLY NOW JUST HOW MUCH
REGRESSION IS SEEN IN THIS
MODEL. AS AN EXAMPLE. IN THE
UPCOMING SLIDES I WILL SHOW YOU
WHERE THE RED ARROWS ARE, COUPLE
OF EXAMPLES OF FIXED DATES WHEN
YOU DO ANALYSIS. YOU CAN SEE
HERE ANOTHER WAY THESE TOOL
REPRESENTS THE DATA, IN
GRAPHICAL WAYS IS LOOKING AT FIX
DATES, DAY 7, DAY 21, DAY 30 TO
LOOK AT VARIOUS METRICS. WE HAVE
GROWTH INHIBITION ON THE LEFT,
IN THE MIDDLE IS A WATER FALL
PLOT, ALL THESE ARE THE TWO
SINGLE AGENTS AND COMBINATION OF
THAT, AND ONE OF THE RIGHT IS A
STACKED RESPONSE USING PRC --
PARTIAL REGRESSION, COMPLETE
REGRESSION, PROGRESSIVE DISEASE.
WHAT YOU CAN'T SEE HERE ONE OF
THE RECOMMENDATIONS IS DEPENDING
ON THE DATA YOU PICK YOU CAN
HAVE DIFFERENT OVERALL
INTERPRETATION. IF YOU PICK DAY
7 TO DO ANALYSIS PREDICT PACLA
TAXOL IS DRIVING THE RESPONSE
SEEN IN THIS COMBINATION. BY 21,
DAY 30 THERE IS A BENEFIT TO THE
COMBINATION OVER SINGLE AGE
PACLA TAXOL. GOING INTO A STUDY,
HAVING CLEAR THOUGHTS OF WHAT
YOU PLAN ON METRIC IS GOING TO
BE AT THE END, NOT TAKING SHOW
BEST RESPONSE IS VERY IMPORTANT
ASPECT TO THIS. THE NEXT SLIDE.
IN ADDITION TO THE GRAPHICAL
REPRESENTATIONS THERE ARE
NUMEROUS WAYS TO DO STATISTICAL
ANALYSIS WITHIN THIS TOOL THAT
WILL BE RELEASED. THE METRIC WE
HAVE IN THIS SUITE HAS MULTIPLE
OPTIONS FOR CUSTOMIZATION, SO
DEPENDING ON HYPOTHESIS FOR THE
STUDY KEY INTO THE HELP YOU
NEED. THIS IS A COUPLE OF
EXAMPLES ON THE LEFT IS
OBJECTIVE RESPONSE OR RHESUS CRY
TIERIA. YOU CAN SELECT DAY --
CRITERCRITERIA. YOU CAN SELECT F
READ OUT TO GET A PREDICTION OF
OVERALL RESPONSE FOR THE AVERAGE
OF THE GROUPS. ON THE RIGHT IS
TRADITIONAL WATER FALL PLOT.
THERE'S DIFFERENT SELECTIONS YOU
CAN DO FOR TYPE OF WATER FALL
SHOW RESPONSE FOR THOSE. NEXT
SLIDE. THIS IS AN EXAMPLE OF
EVENT FREE SURVIVAL YOU CAN
THRESHOLD THIS, THIS IS SURVIVAL
TO TUMOR QUADRUPLING, ON THE
RIGHT YOU SHOWS PULL DOWN WHERE
THAT TUMOR HAPPENED IN EACH
GROUP. SO YOU CAN LOOK HOW MANY
DAYS TOOK FOR THAT TO GET WILL
TO FEEL FOR THE DELAY IN
RESPONSE FOR THOSE WHEN YOU HAVE
ACTIVITY FROM DRUG RESPONSE.
NEXT COUPLE OF SLIDES, I WILL
SHOW YOU COUPLE OF THE KEY
RECOMMENDATIONS THAT CAME OUT OF
THIS EFFORT. IT IS REALLY
IMPORTANT THE RECOMMENDATIONS IN
THE MANUSCRIPT, THE ANALYSIS
DONE BY DR. BERNSTEIN AND TEAM
IS AMAZE FOR COMPARATIVE DATA
AND ALL DOES THIS WITH THE TOOL
THAT IS RELEASED. THOSE WORK IN
PDX UNDERSTAND THESE
RECOMMENDATIONS CLEARLY, YOU GO
THROUGH PUBLICATIONS WE ALL SEE
GAPS. USING CLINICALLY RELEVANT
DOSES AND SCHEDULES WHEREVER
POSSIBLE IS IMPORTANT WHEN YOU
CAN TRANSLATIONAL EFFORT MAKING
SURE YOU MONITOR BODY WEIGHT
WITHIN THE TOOL WE DO WE ALLOW
BODY WEIGHT TO UPLOAD THE BODY
WAY GRAPHLY WITHIN TOOL, IF YOUR
SIGNALING RESPONSE IS NOT
SUBSTANTIAL TOXICITY FROM THE
DRUG IN THE ANIMAL ITSELF. TWO
NUANCES MAKING SURE YOU HAVE
CLINICALLY MEANINGFUL ANTITUMOR
ACTIVITY. YOU CAN SEE A
STATISTICAL DIFFERENCE DEPENDING
WHAT CUT OFF YOU USE, IF YOU
HAVE TWO PROGRESSIVE DISEASE
MODELS YOU CAN HAVE
STATISTICALLY DIFFERENCE AND
FEEL YOU HAVE IMPROVEMENT WE
WANT TO LOOK FOR CLINICALLY
MEANINGFUL ACTIVITY WHERE YOU
ARE SEEING TUMOR REGRESSION OR
PROLONGED GROWTH INHIBITION. SO
USING THAT AS A STRONGER METRIC,
WILL HELP IMPROVE AND MAKING
SURE TWO OR MORE METRICS, NOT
USING RHESUS CRITERIA, AND THANK
YOUER MORE GROWTH INHIBITION,
YOU ARE DEPTH AND DURABILITY OF
RESPONSE IN THAT PRE-CLINICAL
STUDY. NEXT. FINALLY, IN
COMBINATION STUDIES, MAKE SURE
BOTH SINGLE AGENTS ARE
REPRESENTED AS CONTROLS SO YOU
CCANSHOW THE TREATMENT ACTIVITYS
ENHANCEMENT OVER SINGLE AGENT
ALONE OR VEHICLE CONTROL. THEN
FINALLY, DEMONSTRATING THAT
DEMONSTRATING ACTIVITY AT LEAST
TO RELEVANT MODELS MORE IF
POSSIBLE, THERE'S BUDGET
CONSTRAINTS ON THIS BUT DON'T --
WE DON'T WANT TO SEE ACTIVITY IN
SINGLE MODEL AT LEAST HAVE TWO
CLINICALLY RELEVANT TO QUESTION
BEING ASKED WITH AGENTS BEING
USED. THERE ARE MULTIPLE
RECOMMENDATIONS IN THIS
MANUSCRIPT. THAT GOES PAIRED
WITH THIS SUITE OF TOOLS
AVAILABLE THAT WILL BE COMING
OUT FOR THE COMMUNITY TO USE IN
THE NEAR FUTURE. NEXT SLIDE. TWO
QUICK ACKNOWLEDGMENT SLIDES, ALL
THIS EFFORT FROM THE PDX HAS
BEEN ASTOUNDING. THEY ARE A
COLLABORATIVE NETWORK AND
WONDERFUL TO WORK WITH. IN BEING
SPEARHEADED BY GREAT OVERSIGHT.
THANKS FOR ALL THE WORK ON THE
PDMR SIDE TO THE GROUPS THAT DO
ALL THIS EFFORT AS WELL AS
CLINICS AND PATIENTS AND
FAMILIES. THANK YOU, WE WILL
TAKE QUESTIONS.
>>THANKS VERY MUCH, THAT WAS A
GREAT PRESENTATION. TO A PERSON
WHO USED ANIMAL MODELS MOST OF
MY CAREER, I COMMEND YOU, IT IS
REALLY VERY NICE. SO OPEN UP
FOR QUESTIONS. I SEE MARY.
>>THANK YOU, VERY MUCH. JIM,
ENJOYED LISTENING TO ALL IS THE
WONDERFUL WORK THE PDX MODELS
AND I WONDERED, I HAVE TWO
QUESTIONS, IF THE RESEARCHERS
REQUEST SOME OF THE ORIGINAL
CLINICAL SAMPLE. THE SECOND PART
OF THE QUESTION IS, WITH THE
WONDERFUL RECOMMENDATIONS YOU
ARE DEVELOPING WHICH IS VERY
IMPORTANT, WILL YOU SHARE THAT
WITH NCATS GENERAL ASSAY MANUAL,
THEY PUT OUT GUIDELINES FOR
RESEARCHERS DOING ROBUST ASSAYS?
>>THE SECOND I'M AWARE OF, AND
HADN'T THOUGHT ABOUT AND IT IS A
GREAT IDEA. WE WILL CERTAINLY
DO THAT. NCATS DOESN'T DO IN
VIVO. THEY DO CONTRACT STUFF BUT
INTERNALLY THEY DON'T SO THAT
WOULD BE VERY USEFUL. WITH
RESPECT TO THE PRIMARY TUMOR.
LET ME SAY I WOULD LOVE TO DO
THAT BUT ABOUT 40% OF OUR
SAMPLES ARE ACTUALLY 18 GAUGE
NEEDLE BIOPSIES THAT ARE BAUERLY
ENOUGH TO EVEN GET PDX STARTED.
UNFORTUNATELY WE COULD NEVER --
THERE IS NOTHING LEFT TO SHARE.
HALF, A LITTLE MORE, SURGICAL
SAMPLES. AND THEY ARE NOT
ENORMOUS. WE -- I HAVE TO SAY I
WOULD LOVE TO BE ABLE TO GIVE
THOSE AWAY BUT WE HAVE OTHER
MECHANISMS TO GET PEOPLE PRIMARY
TUMORS. CHTN AND OTHERS. WE HAVE
NOT OFFERED THE INITIAL BIOPSY
SPECIMEN OR WHICH WE DON'T
REALLY DON'T RETAIN. OR SURGICAL
SPECIMENS TO SHARE.
>>I HAVE ONE ADDITIONAL THING.
IF WE HAVE RESIDUAL PATIENT
TISSUE WE ARE TRYING TO CREATE
DIFFERENT MODEL TYPES WE DO HAVE
WHOLE EXOME RNA SEQ DATA ON THE
DATABASE FOR THAT ORIGINAL
PATIENT MATERIAL. SO WE HAVE
THAT DATA WHEN WE HAVE
SUFFICIENT TUMOR MATERIAL LEFT
OVER TO DO THAT.
>>ALISON O.
>>I'M COMING ABOUT THIS FROM A
SLIGHTLY DIFFERENT PERSPECTIVE
BECAUSE I WORK IN BIOBANKING. AS
WELL. WHAT YOU HAVE DESCRIBED
HERE IS A VERY FASCINATING
APPROACH TO REALLY LEVERAGING
EVER PRECIOUS TUMOR SAMPLE YOU
GET. THIS IS ON TESTIMONY OF
ISSUES OF GETTING OUT THE WORD.
IF REPRESENTATIVE THIS PATIENT
DERIVED MODELS REPOSITORY WOULD
BE INTERESTED IN GIVING A
WEBINAR TO BOTH ISBR AND SOCIETY
FOR CRYOBIOLOGY ABOUT THIS
INITIATIVE FROM PERSPECTIVE OF
BIOBANKING. EVERYTHING,
ORGANOIDS, PDX, CANCER
ASSOCIATED FIBROBLAST, THIS IS A
FASCINATING APPROACH AND OUR
COMMUNITY NEEDS TO LEARN MORE
ABOUT IT. IF YOU ARE AMENABLE,
REACH OUT VIA EMAIL OR CONNECT
ME WITH WHOM EVER IS APPROPRIATE
AND WE WOULD LOVE TO EXTEND
INVITATION.
>>WE WOULD BE DELIGHTED, WE
HAVE DONE HATE TO SAY IT BUT
WHEN I GIVE THIS PRESENTATION,
WE THINK AS AN ADVERTISEMENT
BECAUSE WE ARE INTERESTED IN
DISTRIBUTING, IT IS A HUGE
AMOUNT OF WORK AND WE WANT AS
MANY RESEARCHERS AS POSSIBLE TO
TAKE ADVANTAGE OF THE FACILITY.
>>IN PARTICULAR WHEN YOU TALK
ABOUT YOU GET THESE FIND NEEDLE
ASPIRATES AND YOU ARE OKAYING
OUT EVERY PRECIOUS CELL YOU CAN
FROM THEM, THAT WISDOM, THAT
WORK FLOW IS TREMENDOUSLY
VALUABLE TO THE COMMUNITY. I
VIEW THIS AS AN IMPORTANT
OPPORTUNITY NOT JUST TO EXPOSE
THAT HIDDEN DIAMOND BUT ALSO
PROPAGATE WISDOM AMONG
PRACTICING COMMUNITY.
>>AGREE. RODNEY.
>>THANK YOU, JIM AND YVONNE.
THE IS A VERY GOOD DEMONSTRATION
OF THE DRUG COMBINATIONS
LEARNING ABOUT PHARMACOLOGY AS
WELL AS IMMUNOPHARMACOLOGY IT IS
NOT JUST MOLECULAR MECHANISMS
THAT WE USE TO BE FAMILIARIZED
AND GUIDE DRUG DEVELOPMENT
PROGRAM. SO NALOTNIB IS KINASE
INHIBITORS FOR THE LEUKEMIA,
KINASE INHIBITORS THAT AS THE
TRANSPORTER ACTIVITIES AND WE
INITIALLY THOUGHT THAT WE HAVE A
SLAM DUNK, WHICH WE DON'T. SO
REALLY IS A VERY COMPLEX
CYTOKINE THAT REQUIRE IN VIVO
INTERACTIONS THAT REQUIRE
VALIDATION. NOT ONLY IN THE PDX
MODEL BUT ALSO EVENTUALLY
HOPEFULLY LEARN FROM THIS AND BE
ABLE TO BUILD CYTOKINE
COMBINATIONS OR CELL
THERAPEUTICS. FIRST LESSON. HOW
DO WE DO THIS. IN THE SMALL
SCALE TO LARGE SCALE. YOU
DEMONSTRATED LARGE CLASS
RESOURCES. THAT IS HOW WE SCALE
IT INTO END OF INVESTIGATOR
PROGRAM AND CANCER CENTER, SO
FORTH SO THAT IS REALLY MY
QUESTION. ABOUT HOW WE
DISSIMILARNATE PLATFORM, --
DISSEMINATE PLATFORM. SECOND IS
HOW CAN WE USE THE DATA
GENERATED CELL THERAPY
STANDARDS, THE GUIDANCE OF WHAT
PEOPLE WILL SAY, YOU KNOW, DRUG
COMPANIES, I WANT TO TAKE ON. IF
YOU HAVE X Y Z DATA FOR PROJECT
THAT WE SUPPORT DEVELOPMENT
PROGRAM. THAT IS WHAT I WANT TO
THROW BACK TO THE COMMITTEE
THINK HOW WE CAN GUIDE OVERALL
DIRECTION AND MONICA YOU MAY
HAVE THOUGHTS AS WELL. IT IS
REALLY FASCINATING, IT COMES
TOGETHER CENTERPIECE OF
TRANSLATION THE BASIC ENGINE SO
TO SPEAK.
>>IF I CAN RESPOND, AT LEAST I
CAN REMEMBER QUESTIONS 1 AND 3 I
CAN RESPOND TO. FROM I HOPE
WITHIN A YEAR, MAYBE A YEAR FROM
NOW OR NOT TOO LONG THEREAFTER
WE WILL.
COBACK AND MAKE A PRESENTATION
ABOUT SOMETHING NOT YET READY
FOR PRESENTATION BUT HAS BEEN
SOMETHING WE HAVE BEEN WORKING
ON FOR NOW OVER TWO YEARS. TO
DEVELOP -- TAKE ALL THOSE
ORGANOIDS AND TO DO TRUE HIGH
THROUGH PUT SCREENING SYSTEM FOR
ORGANOIDS. THERE ARE LOTS OF
PAPERS BUT FEW ARE REALLY TRUE
HIGH LIEU PUT SCREENS. NOT ONLY
DO WE HAVE OVER 500 INVALIDATED
ORGANOIDS AND MORE EVERY DAY BUT
WE ALSO HAVE AT FREDERICK A
REPOSITORY FOR SEVERAL THOUSAND
INVESTIGATIONAL COMPOUNDS WE
PURCHASE OFFER MADE OURSELVES
THAT REALLY CONSTITUTE ALL OF
THE INTERESTING COMPOUNDS THAT
-- SINCE THE GOVERNMENT PRODUCED
THEM, SYNTHESIZED THEM OR
PURCHASED THEM CAN BE USED WITH
FOR ANY PURPOSE OF HELP AND THE
GOAL OF THIS WHOLE EFFORT, THIS
IS WHAT I HOPE TO PRESENT TO YOU
IN A YEAR OR SO, IS TO SAY THE
NCI 60 WAS FINE IN 1990. BUT WE
SPECIFICALLY CHOSE NOT TO
DEVELOP EQUIVALENT OF NCI 600,
TO NOT DO THAT WITH OLD PLASTIC
ASSOCIATED CELL LINES. THE GOAL
IS ACTUALLY TO HAVE A THOUSAND
ORGANOIDS PLUS IN CASSETTES THAT
WE WILL OFFER TO THE PUBLIC. TO
THE EXTRAMURAL RESEARCHERS YOU
HAVE TO APPLY, NOT FOR MONEY,
BUT FOR PROJECT IT IS WAY WE DO
IN OTHER KINDS OF AREAS IN THE
NEXT PROGRAM AND HAVE EXTERNAL
REVIEW AND THEN IF YOU HAVE
PARTICULAR PROJECT OR TARGET OR
COMPOUND YOU WANT TO COMBINE
WITH ANYTHING IN OUR REPOSITORY
WE WILL DO IT FOR YOU AND FIEF
YOU THE DATA. WE MADE A LOT OF
PROGRESS, SO FAR WE HAVE A PANEL
IN COLON, PANCREAS, WE WANT TO
HAVE SEVERAL MORE PANELS WE CAN
OFFER TO PUBLIC. BUT THE GOAL IS
NO COST OFFER THESE THINGS AFTER
PEER REVIEW TO THE EXTRAMURAL
COMMUNITY TO DO EXACTLY WHAT WE
SAY, TO ADVANCE IDEAS THAT
PEOPLE HAVE PROVIDE PRELIMINARY
DATA SO THEY CAN GO BACK AND DO
THINGS IN THEIR LABORATORY THAT
WOULDN'T ORDINARILY BE EASILY
ACCOMPLISHABLE.
>>ANANT, DID YOU HAVE A
QUESTION?
>>WONDERING IF THERE IS AN
OPPORTUNITY WITH THE TISSUE THAT
IS BEING ACQUIRED, WHETHER THERE
IS OPPORTUNITY TO DIGITIZE THE
SLIDES AND TO THINK ABOUT
CREATING A SLIDE REPOSITORY,
ADDITIONAL SLIDE REPOSITORY THAT
CORRESPONDS TO THESE SUBSEQUENT
PDX MODELS AND ORGANOIDS BEING
CREATED.
>>POSSIBLE. THE HNEs ARE
ACTUALLY ZERO COST DOWNLOADABLE
FROM THE WEBSITE. SO WE HAVEN'T
HAD RESOURCES YET TO INVEST IN
DIGITIZING THEM AT LEAST --
DIGITIZING THEM, AT LEAST ALL OF
THEM, SOME OF THE PDX MODELS I
DIDN'T HAVE CHANCE TO TALK ABOUT
IT, WE DO INTENSE SMALL ANIMAL
IMAGING. THOSE SMALL ANIMAL
IMAGING WHETHER MR OR
ULTRASOUND, AS WELL AS HISTOLOGY
IS UPLOADED TO THE TCIA. SO
ABOUT 50 MODELS QUITE
COMPREHENSIVE ANALYSIS OF ALL OF
THAT DATA FROM THE MODELS SO THE
GENETIC DATA IS AVAILABLE. THE
IMAGING DATA IS AVAILABLE AS
PART AND PARCEL OF THE TCIA.
>>BEFORE I GO TO JOHN FOR THE
LAST QUESTION, DOUG DID YOU HAVE
A COMMENT PERTINENT?
>>YES. THIS IS UNSOLICITED
ENDORSEMENT AS AN END USER OF
THE PDMR BUT A DIFFERENT AREA,
JIM AND YVONNE TALKED ABOUT THE
CRITICALLY IMPORTANT AREA OF
CANCER TREATMENT FOR EVALUATION
BUT IN MY LAB WE ARE ESPECIALLY
INTERESTED IN MUTANTS. BECAUSE
THE DATABASE HAS BEEN SUBJECT TO
GENOMIC SEQUENCE ANALYSIS, THE
TWO THINGS I WILL TELL YOU ARE
FIRST, KRAS G 12C MUTATIONS ARE
UNCOMMON IN PANCREATIC CANCER
BUT THERE ARE SEVERAL PANCREATIC
CANCERS WITH G 12C MUTATIONS SO
THAT IF YOU WANTED TO LOOK AT
THAT IN THE CONTEXT OF A PDX, IT
IS VERY EASY TOE DO SO. THEN WE
ARE STUDYING AN UNUSUAL BUT
RECURRENT MUTATION INVOLVING ROW
GTPASES, IT TOOK YVONNE LESS
THAN 30 SECONDS TO SAY THAT IN
THE DATABASE THERE IS A CANCER
WITH THIS UNUSUAL RECURRENT
MUTATION. WHICH THEREFORE WE ARE
ABLE TO STUDY.
>>THANK YOU FOR THE COMMENT.
LAST QUESTION FROM JOHN.
>>THIS IS A FANTASTIC RESOURCE.
I WANT TO ASK, I THINK ONE OF
THE REALMS WHERE THIS COULD HAVE
EXTRAORDINARY IMPACT IS IN AS
YOU HIGHLIGHT WITH THE SARCOMAS,
MORE RARE CANCER WHERE IT IS
MUCH HARDER TO FIND THESE
SAMPLES AND FIND MODELS TO WORK
WITH. IS THERE A FOCUS ON THAT
IN PARTICULAR?
>>ABSOLUTELY. WE HAVE
ENCOURAGED AS I IMPLIED IT WAS
EASIER TO GET THOSE SAMPLES FROM
ACADEMIC CENTERS MANY TIMES THAN
GET STAMPED AND GET STANDARD
BREAST CANCER BECAUSE NOT EVERY
CENTER HAS INVESTIGATOR WHO IS
INVOLVED IN STUDYING SYNOVIAL
SARCOMA FOR EXAMPLE SO THEY ARE
WILLING TO SEND US THOSE MODELS.
WE CAN THEN MAKE THEM AVAILABLE
TO THE COMMUNITY.
>>THAT IS GREAT.
>>WE DO STILL HAVE -- WE HAVE A
LITTLE BIT MORE TIME BEFORE WE
GO ON A BREAK. ANYBODY HAVE A
LAST MINUTE QUESTION OR COMMENT
LINDA.
>>CURIOUS WHETHER YOU HAD
RELATIONSHIP OR WHETHER YOU CAN
INCORPORATE SOME OF THE OTHER
MAJOR DATA CENTERS, FOR INSTANCE
SAINT JUDES WITH CHILDREN'S
TUMORS IN A PARTICULAR BRAIN
TUMORS, THEY HAVE QUITE A
COLLECTION THEMSELVES AND
WONDERING WHETHER SOME OF THOSE
COULD BE BROUGHT INTO SHARED
DATABASES.
>>ONE OF THE THINGS WE HAVE
DONE, THE ANSWER IS YES, WE HAVE
A MECHANISM TO DO THAT. NOT ONLY
HAVE WE PRODUCED LOTS OF MODELS
OURSELVES, EACH PDX NET
COLLABORATORS IS ALSO PROVIDED
US WITH WE HAVE SEVERAL HUNDRED
MORE MODELS THAT ARE IN FREEZERS
BECAUSE IT IS A MATTER OF KRAS
SPACE AND GROWING THESE UP AND
REANALYZING THEM TO PUT INTO THE
REPOSITORY. SO THAT AS LONG AS
THE PATIENTS HAVE -- IF THEIR
TISSUE WAS COLLECTED IN
ACCORDANCE WITH THE APPROPRIATE
CONSENTING TO ALLOW SHARING
GENETIC ANONYMIZED GENETIC
INFORMATION WE HAVE GOTTEN -- WE
WERE RECENTLY GOT A COLLECTION
OF CLANGIAL CARCINOMAS FROM NGH
AND THE INVESTIGATOR WAS HAPPY
TO SHARE THEM BECAUSE HE HAD NO
WAY OF LONG TERM STORAGE FOR
THOSE. HE USES THOSE FOR THOSE
OWN INVESTIGATIONS BUT THEY WILL
BE AVAILABLE TO THE GREATER
COMMUNITY. THEY ARE TAKING ON
COLLECTIONS THAT OTHER
INVESTIGATORS MIGHT HAVE HELP
WITH IN TERMS OF DISTRIBUTION.
>>GREAT. REMARKABLE. OKAY. SO
WE ARE NOW TAKING A BREAK. WE
WILL HAVE ADMINISTRATIVE SESSION
SO THOSE OF US THAT ARE ON THE
VIRTUAL WEBEX SHOULD NOT
DISCONNECT. EVERYONE ELSE SHOULD
TAKE A 30 MINUTE BREAK. THE
MEETING WILL RESUME PROMPTLY AT 1:20
>>WE HAVE THE FREDERICK
TECHNOLOGY SHOWCASE THAT'S GOING
TO BE PRESENTED TO US, BY DR.S
SALGALLER AND POPOV. I DON'T
KNOW WHO IS GOING FIRST.
>>HELLO. MICHAEL YOU ARE
PULLING UP THE SLIDES, RIGHT?
>>I.
A. -- I AM.
>>GOOD AFTERNOON, EVERYONE.
THANK YOU FOR THE OPPORTUNITY TO
PRESENT ON THAT SHOWCASE. MY
NAME IS VLADMIR POPOV, CHIEF
OFFICER FOR CANCER RESEARCH. I
HAVE BEEN WITH THE LAB SEVEN
YEARS, HELD SEVERAL ROLES. BUT
ALWAYS FOCUSING ON COLLABORATION
AND PARTNERSHIP DEVELOPMENT
OUTREACH AND PROGRAM SUPPORT.
I'M PLEASED TO BE HOAR TODAY AND
LOOKING FORWARD TO PRESENTING
TECHNOLOGY SHOWCASING TO WITH
MICHAEL. I WILL NOW LET MICHAEL
INTRODUCE HIMSELF.
>>THANK YOU VERY MUCH FOR
HAVING US PRESENT. I'M MICHAEL
SALGALLER, I ACTUALLY PART
STARTED MY CAREER AT THE NCI
POST-DOCKING WITH DR. JOE
SCHROENN IN THE LABORATORY OF
TUMOR IMMUNOLOGY AND BIOLOGY AND
WENT ON TO WORK FOR SEVERAL
YEARS WITH DR. STEVE ROSENBURG.
LEFT TO LEAD SEVERAL LIFE
SCIENCE COMPANY, WORK IN VENTURE
CAPITAL TO HELP OTHERS START
COMPANIES AND CAME BACK TO HEAD
THE TECHNOLOGY ANALYSIS
MARKETING UNIT ABOUT SIX YEARS
AGO. IT ALL STARTED WHEN VLAD
AND TEAM AND MY TEAM MET WITH
REPRESENTATIVES FROM FREDERICK
COUNTY AND CITY LATE 2016, THEY
WERE INTERESTED IN CREATING
BETTER UNDERSTANDING AND
AWARENESS OF THE EXCITING CANCER
RESEARCH BEING DONE AT THE
FREDERICK NATIONAL LAB AND SO
ONE OF US INNOCENTLY SAID WE
COULD ALWAYS PUT ON A MEETING.
IT IS SORT OF IN A GOOD WAY
STEAM ROLLED FROM THERE. OUR
INAUGURAL YEAR WAS A HALF DAVID
IN 2017. IN 2018 WE EXPANDED TO
A FULL DAY AND ADDED KEY NOTES,
WE ADDED THE TECH TRANSFER
AMBASSADORS PROGRAM WHICH VLAD
WILL DESCRIBE IN A FEW MINUTES.
ALSO POSTER PITCHES POSTERS THAT
TALKED ABOUT NOT JUST AS THE
SCIENCE BUT THE PARTNERING
OPPORTUNITY P. THEN IN 2019
BASED ON FEEDBACK WE RETURNED TO
HALF DAY FORMAT. AND INCLUDE
PANELS ON VARIOUS TOPICS THAT
VLAD WILL SUMMARIZE. IN 2020 WE
PIVOTED TO A VIRTUAL
OPPORTUNITY, WE EXPANDED OUR
OUTREACH OUTSIDE OF THE DMV AND
HAD SIX COUNTRIES AND 13 STATES
PARTICIPATE AND WERE FORTUNATE
ENOUGH TO WIN THE NCI DIRECTORS
AWARD THAT YEAR. IN 2021, WE
ADDED THE VOICE OF THE PATIENT,
HAD A FULLY VIRTUAL EVENT AGAIN,
WE ARE FORTUNATE ENOUGH TO WIN
THE FEDERAL LAB CONSORTIUM
AWARD, FOR SATE AND WILLCAL
ECONOMIC DEVELOPMENT. THIS PAST
YEAR WE DID OUR FIRST HYBRID
EVENT, VIRTUAL AND IN PERSON, WE
INCLUDED PROGRAMMATIC
PRESENTATIONS THAT GAVE OVERVIEW
OF RESEARCH PROGRAMS AND
BRANCHES RATHER THAN INDIVIDUAL
TECHNOLOGIES. AND HAD NEARLY 300
ATTENDEES.
>>THANK YOU, MICHAEL. YOU WILL
HEAR US CALLING THIS EVENT
UNIQUE THROUGHOUT THE
PRESENTATION. AND IT TRULY IS A
UNIQUE AND JUST A FEW REASONS WE
SEE IT AS SUCH. IT IS FIRST THE
ONLY NIH CONFERENCE WITH
POTENTIAL LICENSEES AND
COLLABORATORS AT PRIMARY
AUDIENCE WITH AGENDA THAT
ADR.sS INTEREST AND WE DO
TECHNOLOGY PITCHES WITH A
BUSINESS CASE RATHER THAN
SCIENTIFIC PRESENTATIONS WE
KEYNOTE ADDRESS, VOICE PATIENTS
SUCCESS STORIES INDUSTRY FOCUSED
PANELS AND NETWORKING. ALL WHICH
WILL COVER MORE DETAIL. WE HAVE
CO-SPONSORSHIP AGREEMENT WITH
ECONOMIC DEVELOPMENT OFFICES OF
FREDERICK COUNTY AND CITY AND
ALSO TECHNOLOGY DEVELOPMENT
CORPORATION, SPECIFIC TO
MARYLAND FUNDING AND THIS IS TO
LEVERAGE RESOURCES RELATIONSHIPS
AND EXPERTISE. THIS IS ONE OF
THE EVENTS THAT GIVES PI
OPPORTUNITY TO DEVELOP BUSINESS
CASE PRESENTATION, WE WILL COVER
THIS IN MORE DETAIL WHERE WE
WILL SHOW WHAT PRESENTATION WE
EXPECT PIs TO GET. THIS IS
MENTORED BY TECH ANALYSIS IN THE
MARKETING UNIT FROM NCI SIDE AND
PARTNERSHIP DEVELOPMENT OFFICE
OUTSIDE. FINALLY WE HAVE A
TECHNOLOGY TRANSFER AMBASSADORS
PROGRAM. THIS ALLOWS AMBASSADORS
TO PRESENT QUICK INVENTION
PITCHES AND POSTERS FOR
POTENTIAL COMMERCIAL PRODUCT
PERSPECTIVE. WITH OUR MISSION
AND OUR NCI FOCUSING ON CANCER
RESEARCH AND ADVANCE SCIENTIFIC
NEW YORK FOR BENEFITS OF PUBLIC
HEALTH WE DESIGNED A SHOWCASE TO
ADDRESS THE GAP ACTIVITIES FOUND
IN FEDERAL LABS AND TECHNOLOGY
SHOWCASE PROVIDES A MENU FOR NCI
AND FNL TO SHOWCASE THEIR UNIQUE
CAPABILITIES EXPERTISE AND
PROMOTE INTELLECTUAL PROPERTY
DEVELOPED IN OUR LAB.
COMMERCIALIZATION AND FURTHER
DEVELOPMENT OF THESE
TECHNOLOGIES IS CRUCIAL FOR
MOVING THE NEEDLE FORWARD AND
ADVANCING CURRENT APPROACHES IN
CANCER RESEARCH AND TREATMENT.
IT IS TO RAISING THE AWARENESS
OF IMPORTANT RESEARCH AND
CAPABILITIES AT NCI AS WELL AS
THROUGH BRINGING TOGETHER KEY
PLAYERS CRUCIAL FOR THIS
ECOSYSTEM, THE SHOWCASE
ACCOMPLISHES A FEW THINGS, THESE
ARE IT PRESENTS THE BEST IDEAS
AVAILABLE FOR COLLABORATION AND
LICENSING. IT ATTRACTS R&D
RESOURCES AND COLLABORATORS AND
REPRESENTS THE RETURN ON PUBLIC
INVESTMENT. IT ALSO STIMULATES
AN STRENGTHENING THE DEVELOPMENT
AND ULTIMATELY BENEFITS THE
PUBLIC HEALTH. IT IS A GREAT FIT
WITHIN MARYLAND AND WHY DO WE
SAY THAT? FIRST WE ARE IN
MARYLAND. I GUESS WILL IS THAT
SLIGHT INFLUENCE. MARYLAND IS
ALSO A STATE WITH LARGE
CONCENTRATION OF MAJOR
GOVERNMENT FUNDED RESEARCH. IT
IS NUMBER ONE IN NIH R&D
CONTRACT AWARDS, NUMBER ONE
STATE SCIENCE TECHNOLOGY WORK
FORCE AS WELL AS PLOYED DOCTORAL
SCIENTISTS. MARYLAND HAS
CLIMBED UP THE LADDER IN LIFE
SCIENCES AND BIOTECH. THERE ARE
ABOUT 3400 LIFE SCIENCE
BUSINESSES IN MARYLAND. FINALLY
SINCE THE SHOWCASE IS NOT ONLY
LOCAL STATE AND REGIONAL EVENT,
MARYLAND VIRGINIA AND DC TRIO IS
NUMBER FOUR BIOHEALTH CAPITAL IN
THE UNITED STATES YOU CAN ASSUME
THAT THE BAY AREA, BOSTON NEW
YORK IN FRONT OF US BUT EVERYONE
ELSE IS BEHIND. SO TALKING ABOUT
-- I WANT TO ADDRESS WHY IS THIS
A GOOD FIT WITHIN FREDERICK
COUNTCOUNTY. THIS IS WHERE FREDK
NATIONAL LAB IS LOCATED.
FREDERICK NATIONAL LAB IS TOP
EMPLOYER FREDERICK. PREED RICK
COUNTY HAS HIGH CONCENTRATION OF
GOVERNMENT FUNDED RESEARCH, WE
HAVE NATIONAL LAB, NATIONAL
CANCER INSTITUTE, ARMY AND MANY
MORE PRESENT AT FORT DETREICH.
ELONZA, KITE AND MANY OR SETTING
UP R&D AND MANUFACTURING
HEADQUARTERS HERE. THERE IS OVER
100 LIFE SCIENCE COMPANIES IN
FREDERICK, THIS IS GROWING
RAPIDLY WITH THE COUNTY NUMBER
ONE STRATEGIC GOAL BEING LIFE
SCIENCE RESEARCH. THIS IS
PRESENTED MARYLAND AND FREDERICK
COUNTY ARE REASONS WHY WE
SUCCESSFULLY PARTNERED WITH
FREDERICK ECONOMIC DEVELOPMENT,
COUNTY, CITY AS WELL AS IF ED
RAIL LAB CONSORTIUM. THIS IS TO
SHOW IT TRULY TAKES A VILLAGE TO
PUT SOMETHING TOGETHER SUCH AS
SHOWCASE AND MAKE IT SUCCESSFUL
BUT PARTNERING WITH ECONOMIC
DEVELOPMENT THE CITY LABS AND --
WE FURTHER BUILT AND STRENGTHENS
THOSE RELATIONSHIPS AND ABLE TO
LEVERAGE THEM. WE WERE ABLE TO
DIRECTLY REACH BIOTECH PHARMA
AND STARTUPS ON BOTH LOCAL AN
REGIONAL LEVEL. WE HAVE NETWORKS
BUT BY PARTNERING WE WERE ABLE
TO QUADRUPLE OUR CAPABILITIES
AND POSITION OURSELVES AS LEAD
FOR FEDERAL WORLD. WE E AND AND
STRENGTHENED OUR RELATIONSHIP
WITH FERAL LABS AND ACADEMIC
INSTITUTIONS, PROVIDING OTHER
BENEFITS TO NCI SUCH AS BEST
PRACTICES FROM OTHER FEDERAL
LABS, EDUCATIONAL OPPORTUNITIES
THROUGH PARTNERSHIP WITH
ACADEMIA AS WELL AS WORK FORCE
DEVELOPMENT.
>>WE WERE ABLE TO GET A WIDE
SWATH OF REPRESENTATION FROM THE
OUTSIDE COMMUNITY BY EXPANDING
OUR TARGET AUDIENCE. SO BY USUAL
SUSPECTS WHO DO WE TYPICALLY
PARTNER WITH AND LICENSE TO? WE
DO A LOT WITH PEOPLE WORKING
WITH US, WE CERTAINLY GET A LOT
OF VISITS THROUGH OUR WEBSITE
AND CERTAINLY OUR FACULTY IS A
MAJOR SOURCE OF POTENTIAL
LICENSEES AND PARTNERS. . WHAT
WE HAVE DONE IS EXPANDED TO
OTHER PLACES THAT WOULD BE
RELEVANT FOR US. THAT INCLUDES
NATIONAL AND INTERNATIONAL
COMPANIES OF ALL STAGES FROM
EARLY STAGE ALL WAY THROUGH
PUBLIC. WE LIAISON WITH
INVESTORS WHO BRING IN
TECHNOLOGIES TO START NEW
COMPANIES AS WELL AS THE
ENTREPRENEURS WHO START THOSE
COMPANIES WITH THE INVESTORS. WE
WORK WITH TECH SCOUTS, TYPICALLY
SMALL BOUTIQUE FIRMS THAT HUNT
FOR EXCITING TECHNOLOGIES, HALF
OF USUALLY LARGE FAR MASS OR
BIOPHARMAS. THEY ARE DIRECT
POTENTIAL PARTNERS AFTER WE
CREATE AWARENESS. WE HAVE GONE
BEYOND THAT TO WORK WITH TRADE
ASSOCIATIONS, ECONOMIC
DEVELOPMENT ENTITIES,
FOUNDATIONS AND PHILANTHROPIES
AND SERVICE PROVIDERS, LAW FIRMS
CONSULTING FIRMS, REGULATORY
FIRMS. THEY CAN PROVIDE
REFERRALS TO COMPANIES THAT WE
MIGHT BE ABLE TO WORK WITH. ONCE
WE CREATE THAT AWARENESS. SO
BASED ON 2022 THIS GIVES A
LITTLE BREAK DOWN WHO ATTENDED.
ABOUT HALF WERE FROM NIH AND
THAT IS IN SOME PART BECAUSE WE
HAVE SO MANY PARTICIPANTS ON
ACTIVITIES, PIs, THE TECH
TRANSFER AMBASSADORS ET CETERA
SO THAT MAKES UP A GOOD COHORT.
WE HAVE HAD 26% COMPANIES, I
WOULD ADD MOUSES 10% AND OTHER
CATEGORY BECAUSE MOST OF THESE
WERE INDIVIDUALS WHO REGISTERED
USING THEIR PERSONAL ADDRESS AND
WE FIND THAT THE VAST MAJORITY
OF THEM ACTUALLY REPRESENT
COMPANIES THAT ARE IN STEALTH
MODE AND DON'T WANT TO REVEAL
WHO THEY ARE. SO THE NUMBER IS
CLOSER TO 30 TO 35%. WE HAVE
UNIVERSITIES ATTEND ESPECIALLY
TO THE FREDERICK REGIONFUL WE
GET ECONOMIC DEVELOPMENT
ENTITIES AS WELL AS FOUNDATIONS
ACCELERATORS AS WELL AS
INVESTORS. TO DO THAT, WE
CREATED A INTERNATIONAL NETWORK.
THIS MAP REPRESENTS NOT JUST
FOLKS WE HAD RANDOM PHONE CALL
WITH, THEY REPRESENT FOLKS THAT
ACTIVELY HELPED US MARKET THE
EVENT GET OUT SO WE HAVE -- WE
LIAISON WITH THESE INSTITUTIONS
AND INTI FEWS TO INDICATE THE
OPPORTUNITIES TO PRESENT GLOBAL
HEALTH AROUND THE WORL WORLD. TS
EVENT ALSO HAPPENS TO SERVE AN
IMPORTANT PURPOSE ABOUT
ADDRESSING SOME OF THE COMMON
MYTHS ABOUT THE NATIONAL
INSTITUTES OF HEALTH. MY TENURE
AT NCI HAD 20 YEARS IN BETWEEN
MY TWO STOPS. AND LEARNING FROM
THE OUTSIDE WORLD ABOUT WHAT
PEOPLE DO AND DO NOT UNDERSTAND
ABOUT THE NIH. UNFORTUNATELY,
AND SOMETHING THAT VLAD AND TEAM
ARE ADDRESSING IS COMMON THOUGHT
ON THE PART OF POTENTIAL
LICENSEES AND PARTNERS WE ONLY
DO BASIC RESEARCH. CERTAINLY
THAT IS A MAJOR FOCUS ON OURS,
HOWEVER, WE DO TRANSLATIONAL AND
CLINICAL WORK AS WELL. THERE IS
A WIDE MISUNDERSTANDING WE
SOLELY WORK WITH ACADEMIA AND
PROVIDE ACADEMIC FUNDING. SO WE
TELL THEM URN CURRENTLY WE HAVE
HUNDREDS OF LICENSING AND
PARTNERSHIPS WITH SRI AND WE
WOULD LOVE TO TALK WITH THEM
ABOUT JOINING THAT GROUP. WE
DON'T JUST WORK IN THE U.S.,
YES, WE ARE FOCUSED ON
FACILITATING ECONOMIC
DEVELOPMENT IN THE U.S. BUT WE
CAN MARINER INTERNATIONALLY TO
ADDRESS GLOBAL HEALTH CONCERNS.
SPARSE OUR IP DOCKET IS
CONCERNED, YES, MAJORITY ARE
UNDER THE CATEGORY OF
THERAPEUTICS. BUT WE ALSO HAVE
DEVICE, DIAGNOSTICS, BIOMARKERS
AND MORE AND WE ALSO DO RESEARCH
IN PREVENTION CONTROL AND CAUSES
OF DISEASES AN DISORDERS. THINGS
BROUGHT THE TO MARKET AND
PATIENT DON'T SOLELY GO TO NCI
AND FNL. COMPANIES BRING IDEAS
TO US AND WE CAN CO-DEVELOP
TOGETHER. VLAD.
>>THANK YOU, SO SWITCHING A
LITTLE BIT TO AGENDA AND
FEATURES OF THE ACTUAL TECH
SHOWCASE WHAT IS A TYPICAL
AGENDA AT A TECH SHOW LOOK LIKE
WE START OFF WITH A KEYNOTE BUT
NOT ANY KEYNOTE. WE HAVE BEEN
TRULY FORTUNATE TO HAVE
REMARKABLE AND INFLUENTIAL KEY
NOTES AT EVERY EVENT SINCE
INCEPTION. JUST NAME A FEW WE
HAD NCI DIRECTOR DR. LOWY AND
DR. SHARPLESS, WE HAD PHARMA
EXECUTIVES DR. JIM CHERRY FROM
NCI, MD MARYLAND COMMERCE
SECRETARY KELLY SCHULTZ AND VIA
HEALTH INNOVATIONS RICH MAENADES
AND OTHERS AS WELL. THOUGH
THECAL BAR OF KEYNOTE COULD BE
EVENT ITSELF BUT WE ADDED MORE
THAT THAT, WE ORGANIZED PANELS,
THESE ARE PANELS THAT ADDRESS
SOME OF THE KEY QUESTIONS, HOW
TO WORK WITH FNL AND NCI, WHAT
ARE DIFFERENCES BETWEEN
GOVERNMENT AND NON-FUNDING, AND
RESOURCES FOR START YOU WERES,
SO ON. WE HAVE PE PRESENTATIONS,
THIS IS SHOWCASE PART OF THE
TECH SHOWCASE. WE PRESENT AND
WE ADVERTISE THESE TECHNOLOGIES
THAT ARE AVAILABLE FOR LICENSING
OR FOR COMMERCIALIZATION OR
COLLABORATION. WE WILL COVER
MORE SEPARATE SLIDE AS FAR AS
WHAT WE EXPECT FROM PIs WHEN
THEY PRESENT. IS WE HAVE
PROGRAMMATIC PRESENTATIONS. WE
HAVE VOICE OF PATIENT, NCI
PROGRAM WE MENTIONED, TALKS
ABOUT AND DEALS WITH NEXT
GENERATION TRAINING AND
NETWORKING. SOME OF THE BENEFITS
THAT ARE SPECIFIC FOR NATIONAL
LAB COME THROUGH AN OPPORTUNITY
TO COMMUNICATE TO SPECIFIC
RELEVANT AUDIENCE. ON THINGS
LIKE HOW TO WORK WITH THE
NATIONAL LAB. WHAT IS NATIONAL
LAB MEAN? WHAT KIND OF
PARTNERSHIPS AND COLLABORATIONS
ARE AVAILABLE AND HOW TO
ESTABLISH THOSE HOW TO APPROACH
NATIONAL LAB. WE TALK ABOUT
UNIQUE PROGRAMS AN CAPABILITIES
AVAILABLE FOR COLLABORATION AND
RESEARCH SUPPORT. PROGRAMS LIKE
RAS PROGRAM, CHARACTERIZATION
LAB, CAPER
CRYOELECTROMICROSCOPY. FINALLY
WE INFORM THE RESEARCH COMMUNITY
OF UNIQUE SERVICES WE PROVIDE.
ONLY FOUND IN FNL. THESE ARE
SERVICES OFFERED FOR TECHNICAL
SERVICE AGREEMENT AND NEEDD BY
COMMUNITY BUT ONLY BE FOUND AT
NATIONAL LAB. THIS IS WHY WE
OFFER THEM. SO I TALKED ABOUT
EDUCATING FNL AND NCI SCIENTIST
AND (INAUDIBLE) PRESENTATIONS
THIS IS THE EDUCATION AND HOW TO
COMMUNICATE WITH INDUSTRY AND
MARKET THEIR INNOVATION. MOST
SCIENTISTS LOVE TO TALK ABOUT
SCIENCE AND GO MANY, MANY SLIDES
OF SCIENCE BUT THIS IS A
DIFFERENT TYPE OF PRESENTATION.
WE LIMIT THEM TO TEN MINUTE
PRESENTATION, WE PROVIDE THEM
WITH TEMPLATES, AND THE
PRESENTATIONS ARE USUALLY ABOUT
EIGHT TO 12 SLIDES THAT INCLUDE
BASE CASE. SO THE TYPICAL --
BUSINESS CASE. IT WILL HAVE
EXECUTIVE SUMMARY, STATE WHAT
THE PROBLEM IS, WE TRYING TO
ADDRESS, WHAT ARE CURRENT
SOLUTIONS OUT IN THE MARKET? AND
HOW DOES SOLUTION THEY ARE
PROPOSING IS DIFFERENT HOW IS IT
DIFFERENT FROM P THE ONES THAT
ARE OUT THERE. WE TALK ABOUT
BACKGROUND AND WE GIVE THEM FEW
SLIDES TO TALK ABOUT IT,
TECHNOLOGY AND SCIENCE. AND THEN
WE ALSO HELP THEM TALK ABOUT
ADDRESSABLE MARKETS AND
OPPORTUNITIES AND COMPETITIVE
ANALYSIS. THEY PROVIDE SUMMARY
AT END WITH CLEAR INDICATION WHO
LICENSING AND PARTNERING POINTS
OF CONTACTS ARE. IS
>>THANK YOU, VLAD. ALSO WANT
TO MENTION PIG BY BACKING ON
COMMENT ABOUT TEN MINUTES FOR
SPEAKERS, BOTH VLAD AND I ARE
RECOVERING SCIENTISTS AND WE
KNOW THAT IT IS COMMON TO RUN
OVER IN TIME AND ONE OF THE MANY
COMPLIMENTS AND ONE COMMON
COMPLIMENT WE GET AFTER THE
EVENT IS PEOPLE SAYING WOW, YOU
FINISHED ON TIME. SO TO HAVE
FIVE AND A HALF HOUR EVEN WITH
NO FEWER THAN 20 SCIENTISTS
SPEAKING AND PRETTY MUCH ON TIME
IS A GREAT EFFORT IN IN AND OF
ITSELF. WHAT DOES THIS MEAN BY
THE BUSINESS CASE? I START OFF
WITH SOMETHING THAT IS SORT OF A
FACTOID COMMONLY GIVEN OUT AND
THE EXAMPLE THE CASE I WILL GIVE
IS ANTIBODY DRUG CONJUGATE
TECHNOLOGY OF BLACKS AND
COUNTRIES LAB AT FNL FOR NEURAL
BLASTOMA, TYPICALLY THAT STARTS
AS FAR AS MARKET BEHIND SIMPLY
SAYING A $10 BILLION MARKET. THE
AUDIENCE WHICH ARE GOING TO BE
INVESTORS ENTREPRENEURS AND
COMPANIES IN THE CANCER SPACE,
KNOW CANCER IS A BIG MARKET,
THERE IS A HUGE SIGNIFICANT
UNMET MEDICAL NEED. A GREAT
FINANCIAL OPPORTUNITY AS WELL.
WE GO BEYOND THAT, THIS IS AN
EXAMPLE FROM DR. ST. CROIX'S
PRESENTATION, MY UNIT AND VLAD'S
GROUP HELPED PI WITH BECAUSE IT
IS NOT THEIR STRENGTH. THIS
GIVES THE DRUG MARKET LANDSCAPE,
AN EXAMPLE OF WHAT WAS PRESENTED
AT THE TECH SHOWCASE. THAT SHOWS
THE DIFFERENT PHASES OF
DIFFERENT TREATMENTS FOR
NEUROBLASTOMA. INDICATES WHICH
ARE THE TOP TEN TARGETS BY DRUGS
AS WELL AS THE MOLECULE TYPES.
IN THE BOTTOM RIGHT ANTIBODIES
BEING QUITE HIGH THAT INDICATES
TO THE AUDIENCE A GREAT APPETITE
MANY THE MARKET AND FROM THE
PATIENT FOR THIS TYPE OF
APPROACH. INSTEAD OF RAP
DOCUMENT FACT HOW MUCH IT IS
GROWING FROM ONE YEAR TO
ANOTHER, WE SHOW THEM FOR
EXAMPLE FOR BRAIN TUMOR, WHICH
NEUROBLASTOMA IS A PART, THAT
THERE IS A GROWING SIGNIFICANT
UNMET MEDICAL NEED FOR THIS. WE
THEN GO ON, THIS IS AN ACTUAL
SLIDE PRESENTED FROM THE
ANTIBODY DRUG CONJUGATE MARKET
LANDSCAPE, THE MARKET
OPPORTUNITY IS THAT SIX ARE FDA
APPROVED SO THE GOOD NEWS IS
THAT FDA HAS SEEN THIS
TECHNOLOGY BEFORE, THERE IS A
PATH, REGULATORY PATH THAT CAN
BE MIMICKED OR SHADOWED BUT
THERE IS ONLY SIX SO LOTS OF
OPPORTUNITIES STILL OUT THERE.
MOST MANUFACTURING IS
OUTSOURCED. THAT IS IMPORTANT
BECAUSE THIS APPEARS TO BE
TECHNOLOGY THAT IS COMPARATIVELY
EASILY MANUFACTURED SEW IT IS A
STRONG MARKET FOR THOSE WHO HAVE
OVER -- WHOSE TECHNOLOGY HAS
OVERCOME THOSE MANUFACTURING
CHALLENGES. WE TALK ABOUT
ADVANTAGES VERSUS OTHER THINGS
AND PRE-CLINICAL, CLINICAL
DEVELOPMENT AND IN GENERAL HAVE
ADVANTAGES SHOWN HERE ENHANCED
EFFICACY, THEY ARE NOT
IMMUNOGENIC AND THAT THERE IS A
BYSTANDER KILLING. IT INDICATES
IT CAN ABLATE TUMOR CELLS AND
TUMOR ASSOCIATED STROMA. THAT
THE CLINICAL TRIAL THOUGH
INITIALLY FOR A RARE DISEASE,
NEUROBLASTOMA, CAN OPEN THE DOOR
FOR BOTH OFF LABEL USE AS WELL
AS USE IN OTHER SOLID TUMORS
THAT COMPANIES FEEL ARE LARGER
MARKET. THIS IS SOMETHING
SIMPLE, VERY KEY AND
UNFORTUNATELY IS NOT OFTEN DONE
IS TYING TECHNOLOGY PRESENTATION
WHETHER HERE OR ACR ASCO TO THE
OPPORTUNITIES SO AFTER TALKING
ABOUT THEIR EXCITING WORK TIMMY
SAY IF YOU THINK THIS WORK IS
COMPELLING TO YOU, YOU CAN WORK
WITH IT. AND WORK WITH ME. OR
YOU CAN LICENSE IT AND SO THAT
IS WHAT WE DO HERE, WE TELL THEM
THE PATENT STATUS OF THE
TECHNOLOGY, WHERE IT IS FILED,
WE INCLUDE THE E NUMBERS, THE
EMPLOYEE INVENTION REPORT
NUMBERS TO EASILY LOOK UP THE
ABSTRACT ON OUR WEBSITE. WE
PROVIDE DIRECT INFORMATION TO
CONTACT THE INVENTOR IF THEY
HAVE TECHNICAL QUESTIONS AND AS
IMPORTANTLY, DIRECT CONTACT
INFORMATION FOR THE TECH
TRANSFER MANAGER WHO IS
RESPONSIBLE FOR THAT INVENTER
AND THAT INVENGES. I ALSO WANT
TO MENTION IT IS A COMPLEX
EVENT. THE AV EVENT STAFF AT FNL
CALLED IT HAIR MOST COMPLEX
EVENT YET. BEPULL IT OFF WITH A
CORE GROUP OF FIVE PEOPLE, THREE
FROM VLAD'S TEAM, MYSELF AND
MICHELLE NEWTON. THERE'S
CERTAINLY OTHERS INVOLVED BUT AS
FAR AS THE CORE, THAT IS WHO IS
DOING A GOOD AMOUNT OF HEAVY
LIFTING. THAT IS FOR 45 SPEAKERS
NOT JUST FROM US, BUT EXTERNAL
ORGANIZES TO IMPLANTING
MEETINGS, ET CETERA, BOTH SIDES
CONTRIBUTE TO HAVING IT
ANNOUNCED FROM THEIR WEBSITE,
MARKETING THE EVENT AND ALSO
DOING SOCIAL MEDIA, POPULATING
AND REHEARSING THE CONCURRENT
PANELS THAT VLAD TOUCHED ON, WE
ALSO HAVE STAKEHOLDER TABLES.
THESE ARE NOT VENDOR TABLES. AS
APPEARS RESEARCH FESTIVAL. THESE
ARE UNIVERSITIES LIKE COLLEGE
MOUNT SATE MARRIES IN THE AREA,
ALSO -- SAINT MARY'S. FNLCR HAS
A TABLE. TECH TRANSFER HAS A
TABLE SO PEOPLE LEARN MORE ABOUT
WHAT GOES INTO LICENSING FROM US
AND PARTNERING WITH US.
EXECUTED WITHOUT BUDGET. THE
MAIN COST EVERY YEAR HAS BEEN
LESS THAN $500. WE CONTRIBUTE
OUR TIME. IT IS IMPORTANT TO
MENTION THAT ALL THE MARKETING
MATERIALS THAT ARE PREPARED AND
SENT OUT, IT IS NOT OUTSOURCED
TO A CONTRACTOR, IT IS ALL DONE
BY VLAD'S PDO AND THE NCI TECH
TRANSFER CENTE CENTER. FORTUNATO
WORK WITH FNL FABULOUS AV AND
EVENT STAFF AND GET TO USE THE
FACILITY AT ATRF AND CO-SPONSORS
KEEP PEOPLE FED AND WATERED
DURING THE AFTERNOON. IT IS VERY
INTRICATE, I SHOW ONE EXAMPLE OF
WHAT WE CALL DIRECTORS NOTES.
THIS IS SIMPLY THE END OF ONE
PRESENTATION AND WHAT HAPPENS
WHEN WE NEED TO IN PERSON AND
VIRTUALLY SWITCH TO OUR FIRST
PANEL SESSION, YOU SEE AUTO TAP
WITH RESOURCE ANSWER WORK WITH
FREDERICK NATIONAL LAB. IT IS
NOT JUST WHO IS PRESENTING BUT
THE ACTION IN THE ROOM AND
VIRTUALLY THAT NEEDS TO BE
TAKEN. NOT JUST WHO IS
CONTROLLING THE SLIDES BUT HOW
SHOWN AND ANY NOTES. THIS GOES
ON FOR EIGHT TO TEN PAGES AND
ALL FIVE AND A HALF HOURS OF THE
EVENT. IT HAS HAD EXCITING
SUCCESS. AND I WILL TURN IT BACK
TO VLAD THE TALK ABOUT THAT AND
WRAP UP.
>>THANK YOU, MICHAEL. MANY
WONDER WHAT OUR POTENTIAL
SUCCESSFUL OUTCOMES OF SUCH AN
EVENT. SUCCESS CAN BE MEASURED
BY MANY INDICATORS BUT WE HAVE
CHOSEN TO SHOW ONE. FIRST THING
YOU NOTICE IS TIME LINE THESE DO
TAKE TIME AND PANDEMIC DIDN'T
HELP. IT STARTED BY CEO OF
(INAUDIBLE) THERAPEUTICS. A
START UP FROM PHILADELPHIA,
MAURICE HAMPTON WHO CAME TO TECH
SHOWCASE AND THEN IN 2019. WHEN
I SAY REGIONAL IT REALLY IS. HE
CAME FROM PHILLY TO ATTEND ONE
OF THE FIRST WE HAD. THIS IS
WHERE WE GOT INTRODUCE AND
STARTED TALKING AND I GOT A
CHANCE TO TELL HIM WHO WE ARE
AND WHAT WE DO, HIS COMPANY WAS
BASED AROUND A DRUG CANDIDATE
AND THROUGH CONVERSATION WE
IDENTIFIED POTENTIAL AALIGNMENT
WITH CAPABILITIES AT OUR CENTER
FOR ADVANCE MEDICAL RESEARCH OR
CAPER. WE CONNECTED WITH OUR
SCIENTISTS AND EXECUTED
COOPERATIVERY SEARCH AND
DEVELOPMENT AGREEMENT. INITIALLY
SLOWED DOWN BY PANDEMIC RESEARCH
IS NOW GOING WELL AND LIKELY
ABOUT TO EXPAND HENCES THE
ARROWS AT END OF THE TIME LINE.
HOWEVER YOU CAN SEE HOW MUTUAL
BENEFICIAL RELATIONSHIP HAS
BEEN. MAURICE IS REGULAR AT
EVERY SHOWCASE EVER SINCE, HE
SERVED AS A PANELIST AND TALKED
ABOUT HIS EXPERIENCE WITH NCI
AND FNL. HE RAISED AWARENESS OF
EVENT IN HIS CIRCLES AND HE IS
CURRENTLY EXPLORING NCI
TECHNOLOGIES FOR HIS PIPELINE.
MORE IMPORTANTLY FOR THE
RESEARCH COLLABORATION OUTCOMES
THAT BENEFIT TECHNOLOGY MAURICE
SECURED ADDITIONAL FUNDING BASED
ON HIS RELATIONSHIP WITH THE
NATIONAL LAB. SO THIS SLIDE IS
SHOW A LITTLE BIGGER PICTURE
BROADER OUTREACH EFFORTS FOR
FREDERICK NATIONAL LAB. WITH THE
EXPANDED PARTNERSHIP TEAM AND
SLOW COME BACK TO IN PERSON
MEETINGS AND EVENTS QUITE A
SUCCESSFUL 2022. OUR TEAM WAS
PRESENT EXTERNALLY FACING EVENTS
AND THIS YEAR WE SERVE AS
KEYNOTE PANELISTS EXHIBITER OR
MEETING ORGANIZER. FOR EXAMPLE
IN BIO THIS YEAR, WHICH IS A
PARTNER IN CONFERENCE, WE MET
WITH OVER 100 BIOTECH COMPANIES,
ACADEMIC INSTITUTIONS, REGIONAL
BIOTECH CENTERS INNOVATION
CENTERS INCUBATORS AND SO ON. AS
PART OF INVOLVEMENT WITH FEDERAL
LAB CONSORTIUM WE MET WITH 20
FEDERAL AND NATIONAL LABS IN THE
MID ATLANTIC REGION. THERE ARE
OTHER NATIONAL REGIONAL AND
LOCAL LISTS WHICH I WILL NOT
READ I PROMISE BUT THAW ARE PART
OFFER COLLABORATION PARTNERSHIP
AND OUTREACH ACTIVITIES. WE
DON'T DO THIS IN ISOLATION. I
MEAN FREDERICK NATIONAL LAB. I
HAVE BEEN AT THE NATIONAL LAB TO
SEE A TRUE GROWTH AND BUILDING
OF THE RELATIONSHIP BETWEEN NCI
AND FNL. THAT IS DEFINITELY A
GREAT EXAM POLL OF PARTNERSHIP
BETWEEN FREDERICK NATIONAL LAB
AND CANCER INSTITUTE AS MICHAEL
SAID WE DO THIS BETWEEN TWO
TEAMS AND WE OVER THE LAST SEVER
YEARS WE HAD CONFERENCES AN
EVENTS PARTICIPATING IN
TOGETHER. WE REFER AND
INTRODUCE COLLABORATORS AND
PARTNERS TO EACH OTHER ALL THE
TIME. I GOT TWO EMAILS THIS
MORNING. TEAMS GROW THROUGH
ACTIVITIES RESULTING IN BETTER
OUTREACH OUTCOMES AND
COMPLIMENTING OF CAPABILITIES.
WITH THAT I WOULD LIKE TO
CONCLUDE OUR PRESENTATION. HAPPY
TO TAKE ANY QUESTIONS.
>>THANK YOU BOTH. SO MUCH. THAT
WAS A VERY DETAILED AND
COMPREHENSIVE PRESENTATION, VERY
IMPRESSIVEMENT QUESTIONS? MARY?
>>WE REALLY ENJOYED THE
PRESENTATION. I WAS WONDERING IF
LIDOSE HAS ANY PARTICULAR ROLE
IN YOUR ACTIVITIES.
>>NOT REALLY NOT SPECIFICALLY
TO TECH SHOWCASE OR ANY
OUTREACH. WE TRY TO KIND OF
SEGREGATE LIDOSE BIOMEDICAL
RESEARCH THAT OPERATES THE LAB,
SO ALL THESE ACTIVITIES OUTREACH
ACTIVITIES AND PARTNERSHIPS THAT
WE DO, ARE FOCUS ON THE NATIONAL
LAB.
>>THANK YOU.
>>RODNEY.
>>THANK YOU. THIS IS IMPRESSIVE
OUTREACH IN BUILDING THE
COMMUNITY TO TRANSLATE IP
GENERATED. I WONDER YOU HAVE A
VERY LIMITED CREW, TO DO THIS.
SO DO YOU HAVE A ASSESSMENT OF
ALL THE IP GENERATED THE COST OF
DEVELOPING THOSE? CALCULATE HOW
MANY HAVE BEEN LICENSED AND
RETURN ON INVESTMENT KIND OF
APPROACH TO LOOK AT AS OUTCOME
MEASURE AND HOW WOULD THAT --
COULD BE IMPROVE WITH ADDITIONAL
INVESTMENT WITH NCI FOR EXAMPLE
>>MICHAEL I WILL LET YOU START
THIS, SINCE NCI IS HANDLING MOST
IP OUT OF FREDERICK NATIONAL
LAB.
>>AS FAR AS RETURN EXAMPLE OF
WHAT VLAD SHOWED, THAT BRINGS IN
CREDA FUNDING. AS FAR AS
EXACTLY HOW MANY AGREEMENTS AND
HOW MUCH BROUGHT INTO THE NCI,
THAT IS A LITTLE BIT DIFFICULT
TO CALCULATE BECAUSE THERE IS
NOT A -- YOU CAN SAY A SLEW FLOW
OF REFERRALS, ONCE WE ARE
INFORMED A COMPANY IS INTERESTED
IN A PARTICULAR TECHNOLOGY AS A
RESULT OF THE SHOWCASE AND WE
THEN TURN IT OVER TO THE TECH
TRANSFER PROFESSIONAL, WE CAN
LOSE WHERE IT GOES FROM THERE,
IF IT GOES FROM THERE. WITH E
KNOW WITH MODEST CAUSE, THAT IT
IS MORE THAN PAID FOR ITSELF
WITH NUMBER OF AGREEMENTS THAT
WE HAVE HAD. EVERY ALSO SEEN A
GREAT UPTICK IN SECONDARY
REFERRALS AS VLAD'S TEAM AS WELL
SO TIME MONTHS LATER WE WILL GET
A REFERRAL FROM SOMEBODY THEY
TALK TO WHO HAVE BEEN TO THE
TECH SHOWCASE. THAT SECONDARY
REFERRAL, AGAIN DIFFICULT TO
DIRECTLY TRACK THAT TO
PARTICULAR AGREEMENT OR LICENSE
AS FAR AS ADDITIONAL RESOURCES,
I THINK THAT WE ARE DOING ALL
RIGHT WITH WHAT WE HAVE. IF WE
ARE ABLE TO -- I WOULD SAY THAT
ACTUALLY IF WE COULD BETTER
LEVERAGE THE OUTREACH AND
COMMUNICATIONS ARM OF NCI
ITSELF, TO BETTER PROMOTE THE
INTRAMURAL PROGRAM, PROMOTE WITH
SMALL P. WE HAVE AN MAZING
FACULTY AND THEY WERE NOT HERLED
NEARLY ENOUGH. IF MORE ATTENTION
COULD BE PAID TO THE AMAZING
WORK DONE THROUGH THE INTERMURAL
PROGRAM THAT WOULD BE GREAT.
VLAD, ANYTHING TO ADD?
>>I WANT TO BRIEFLY ADD
STRAIGHT LINE THAT DOESN'T EXIST
SOMEONE COMING TO THE TECH
SHOWCASE AND NEXT SIX MONTHS
LICENSE WITH ROYALTIES AN
DEVELOPING SOMETHING INTO
PRODUCT. IT MIGHT HAPPEN BUT
THOSE ARE VERY FEW RARE CASES. I
TALKED OVERALL BENEFITS, TOUCH
ON A LOT OF THINGS, IT TOUCHES
ON EDUCATING YOUR NEXT GROUP OF
PROFESSIONALS, BUILDING THE
NETWORK. WE BRING IN PARTNERS
HERE, WORK FORCE DEVELOPMENT,
THEY COME REALIZE ALL THINGS WE
DO AND POTENTIAL TECHNOLOGIES
THEY WANT TO SEND A STUDENT,
THEY EVEN PROPOSE TO PUTTING
CERTIFICATES IN PLACE FOR HARD
TO HIRE AREAS, WITHIN THE LAB
AND NCI. SO THERE ARE MULTIPLE
BENEFITS AND LIKE I SAID, IT IS
NOT USUALLY A STRAIGHT LINE
WHERE YOU CAN CONNECT SOMETHING
WITHIN A YEAR. WITH THAT
EXAMPLE, IT DOES TAKE TIME TO
BUILD THESE RELATIONSHIPS.
>>THANK YOU.
>>THANK YOU. SO THERE IS A
NATIONAL SMALL BUSINESS PANEL
START UP INVESTED BY THE
INSTITUTE CALLED REACH AND THE
CANCER CENTER AS NCI PROOF OF
CONCEPT CENTERS. AND I WONDER
THAT COULD BE INTEGRATED INTO
YOUR THINKING. TO HELP
TECHNOLOGICAL TRANSLATION AS
WELL AS STARTUP THAT FOLLOW ON
COACHING THROUGH GET THE
TECHNOLOGY OUT INTO THE
COMMUNITY FOR PRODUCT
DEVELOPMENT. THAT IS WHAT I AM
THINKING HOW TO INTEGRATE THAT.
>>SURE. WE DEFINITELY WOULD BE
OPEN TO LOOKING INTO THAT. JUST
TO JUMP THAT LAST COMMENT. NIH
SEED OFFICE IS THE NEXUS OF
THOSE EFFORTS. I'M HAPPY TO
CONNECT YOU WITH MATT MCMAHAN OR
SOMETHING BECAUSE IT WOULD BE
HELPFUL TO TAKE ADVANTAGE OF
SOMETHING LIKE THE I CORE AT NIH
OR THAT KIND OF THING TO HELP
YOUR INVESTIGATORS DEVELOP THEIR
VALUE PROPOSITIONS. AND THEIR
BUSINESS CASE.
>>ABSOLUTELY.
>>AGREE.
>>I THINK THAT IS A GREAT IDEA.
THAT IS REALLY BUILT ON TO WHAT
WE ARE TRYING TO DO HERE. WE
LOVE WORKING WITH SMALL
COMPANIES MY PERSONAL PREFERENCE
IS THOSE COME WITH EXCITING
TECHNOLOGIES AND OUT OF BOX
THINKING. IN THE PAST WE HAD
ROAD SHOW WITH SBIR OFFICES AND
TARGETED HOSE COMPANIES AND THEN
WE JUST STARTED TALKING TO THEM
AGAIN AS WE EXIT THIS VIRTUAL
WORLD BACK TO MORE IN PERSON,
WILL DEFINITELY FOCUS ON THAT AS
WELL.
>>THIS IS TOM STACKHOUSE IF I
CAN OBJECT TO THAT LAST COMMENT.
I'M DIRECTOR OF TECH TRANSFER
CENTER HERE AT NCI. SO WE HAVE
WHAT IS CALLED AIM INTERNALLY
WHICH IS THE I CORE PROGRAM AT
NIH. WE DEVELOPED OUR NCI PI AND
WE HAD TWO COHORT NOW, TURNING
OUT QUITE SUCCESSFUL, SEEMED TO
LIKE IT, IT GIVES THEM A UNIQUE
OPPORTUNITY TO LOOK AT RESEARCH
DIFFERENT VENUE. SO TO THAT
QUESTION YES WE ARE MOVING THAT
DIRECTION. THANK YOU FOR THE
COMMENT.
>>COULDN'T BE HAPPIER.
>>LINDA, A QUESTION.
>>I NOTICE YOU MENTION A POST
DOC OPPORTUNITY. WHAT ARE THE
REQUIREMENTS IN ELIGIBILITY FOR
TRAINEES WHO MIGHT LIKE TO BE
PART OF THIS?
>>TALKING THE EVENT ITSELF?
>>YEAH, ANY PAR PART OF IT.
THIS IS AS FAR AS NIH MISSION
FOR TRAINING,ING THIS SOMETHING
A LOT OF OUR ACADEMIC RESEARCH
TRAININGS ARE INTERESTED IN. AS
UNIVERSITIES WE TEND TO BE
LACKING.
>>THIS IS TOM, INKED ADD THE
AMBASSADOR PROGRAM, THE WORK
MICHAEL WAS REFERRING TO WITH
THE SHOWCASE, HAS AN APPLICATION
PROCESS, ANNOUNCED ACROSS NIH,
WE TRY TO REACH OUT AS MUCH AS
POSSIBLE TO THE VARIOUS TRAINING
PROGRAMS AT NIH TO GET
INVOLVEMENT AND EVERY YEAR WE
HAVE ANYWHERE FROM 5 TO 15 FOLKS
WHO JOIN THAT. AND THERE IS A
WHOLE CURRICULUM ACROSS A YEAR
THEY GO THROUGH TO LEARN ABOUT
TECH TRANSFER, ET CETERA. THAT
IS SOMETHING THAT IS NIH -- IT
IS OPENED UP TO NIH TWO YEARS
AGO, WE STARTED HERE AT NIH AND
OPENED UP TO ALL OF NIH TWO
YEARS AGO.
>>ANYTHING ELSE? WE STILL HAVE
A MINUTE OR TWO LEFT.
>>CAN I ASK A QUESTION?
>>YES. PLEASE.
>>SO WANT TO COMMEND PRESENTERS
FOR OUTSTANDING PRESENTATION.
HAVING BEEN AT A FEW
UNIVERSITIES AND WORKING WITH
DIFFERENT TECH TRANSFER OFFICES
I WE SHALL THEY COULD TAKE A
PAGE OUT OF YOUR PLAY BOOK. IT
IS A WONDERFUL WHAT Y'ALL HAVE
DONE. WITH THAT BLONDING ARE IF
I CAN ASK COUPLE OF QUESTIONS,
ONE ABOUT PROCESS. IN GENERAL I
KNOW FACULTY PIs ARE SOMETIMES
UNAWARE OF PUBLIC AT THIS
CLOSURE, VIS-A-VIS --
DISCLOSURE, VIS-A-VIS PATENT
FILING APPLICATION, NOT ALWAYS
CLEAR FOR INVESTIGATORS IS TO WE
ARE HAPPY TO TALK SCIENCE AND
RESEARCH AND ONE OF THE THINGS
WITH IP IS OBVIOUSLY EDUCATION
FOR INVESTIGATORS TO UNDERSTAND
THAT YES YOU ARE EXCITED ABOUT
TECHNOLOGY BUT MAYBE DON'T WANT
TO GO AND PUBLICLY DISCLOSE IT
BEFORE YOU FILE FOR IP. SO
WONDERING WHETHER YOU CAN SPEAK
TO EDUCATIONAL ASPECT FOR PIs.
THEN I THOUGHT IT WAS
INTERESTING THE WAY YOUR
PRESENTING THE IP WITH LINKS TO
SPECIFIC PATENTS. MAYBE IT IS
DIFFERENT IN THERAPEUTICS FOR
THE ONE I LIVE IN WHICH IS MORE
DIAGNOSTIC SPACE. THERE IS THIS
IDEA PULLING TOGETHER PORTFOLIO
OF TECHNOLOGIES AND TRYING TO
MARKET PORTFOLIO VERSUS SINGLE
PATENT OR SINGLE MOLECULE.
AGAIN, COMING FROM A DIAGNOSTICS
PERSPECTIVE. SO WONDERING
WHETHER YOU CAN SPEAK TO THAT
AND HOW YOU GO ABOUT
>>SURE. FIRST ON PI EDUCATION
WE TELL THEM KEEP IT TO PUBLICLY
DISCLOSED INFORMATION. THIS IS
NOT THE AMERICAN ACADEMY OF FILL
IN THE BLANK. YOU ARE SHOWING
SLIDES AND SAY UNPUBLISHED. IT
NEEDS TO BE CENTERED ON
TECHNOLOGY ALREADY FILED. THIS
IS AN OPPORTUNITY FOR AUDIENCE
TO PARTNER WITH AND LICENSE
FROM, SO IT HAS TO BE THAT FAR
ENOUGH IN THE PROCESS AND TECH
TRANSFER MANAGERS IN GENERAL DO
A NICE JOB OF WORKING WITH THE
INVESTIGATORS IN DOCKET TO
DETERMINE IF TECHNOLOGY IS FAR
ENOUGH ALONG TO NEED FOR
EXAMPLE, A STEP OF FILING
DISCLOSURE. WE MACK IT CLEAR
EVERYTHING HAS TO BE PUBLIC
INFORMATION AND WE TELL THE
AUDIENCE THAT THE TECH TRANSFER
MANAGER WOULD BE GLAD TO EXECUTE
A CONFIDENTIALITY AGREEMENT IF
ANY WOULD LIKE THE TALK ABOUT
UNPUBLISHED WORK THE
INVESTIGATOR HAS DONE SINCE THE
FILINFILING. (OVERLAPPING SPEAK)
>>GREAT POINT. OUR GROUP PUT
TOGETHER TECHNOLOGY SHEETS. AND
THEY ARE IN VARIOUS CATEGORIES
SO WE HAVE ONE FOR DIAGNOSTICS
AND SO WE AGREE THAT DIAGNOSTICS
TEND TO BE MORE PLATFORM
SOLUTION. NOT ALWAYS OF COURSE
BUT IF YOU CAN DETECT SOMETHING
ABNORMAL IN DIAGNOSTICS, CELL
THERAPY OR GENE THERAPY, ET
CETERA.
>>OKAY. THANK YOU. DOUG, DID
YOU HAVE A COMMENT?
>>I SIMPLY WANT TO SAY THAT AS
MICHAEL POINTS OUT, IN RESPONSE
TO ALLEN'S QUESTION, THIS IS
RELATIVELY FAR DOWN THE LINE
WHEN IT COMES TO THE ISSUE OF IP
DISCLOSURES, ET CETERA, IN THE
INTRAMURAL PROGRAM WE -- TOM
STACKHOUSE AND TOM MAY WANT TO
COMMENT ON THIS, REALLY THE TECH
TRANSFER CENTER HAS AN ENTIRE
PROCESS IF P AN EMPLOYEE OR
STAFF MEMBER THINKS THAT THERE'S
SOMETHING PATENTABLE WE FILE AN
EMPLOYEE INVENTION REPORT THEN
WILL IS A STANDING COMMITTEE,
TECHNOLOGY REVIEW GROUP, THAT
REVIEWS THESE APPLICATIONS ON
MONTHLY BASIS AND MAKES
RECOMMENDATIONS.
>>YEAH. SO THIS IS TOM. I THINK
THAT SPEAKS TO PART OF WHAT
ANAND WAS ASKING. THIS SHOWCASE
IS FURTHER DOWN THE LINE, SO
THERE'S PROTECTION AROUND IT BUT
RELATED TO THE EIR, OUR
INVENTION REPORTS YOU WERE
ASKING HOW DO WE ENGAGE THE
EMPLOYEES, AWAR OF WHAT NEEDS TO
BE DONE TO OBTAIN A PATENT. IS
THAT WHAT YOU WERE ASKING?
>>IN TERMS OF PROCESS. I AM
WORKING ON SOMETHING COOL, IT
MIGHT BE PATENTABLE,
COMMERCIALIZABLE AND
TRANSLATABLE SO EXCITED TO TALK
ABOUT IT, I BLAST ON TWITTER NOW
PUBLIC DISCLOSURE. SO WE HAVE
TECH TRANSFER MANAGER AND THOSE
MANAGERS ARE ASSIGNED A
PORTFOLIO OF LABORATORIES. AND
THEY ARE IN CONSTANT
COMMUNICATION WITH THOSE PIs,
THEY GIVE PRESENTATIONS FROM
TIME TO TIME TO TALK ABOUT WHAT
IS AN INVENTION, WHAT IS A
COOPERATIVE RESEARCH DEVELOPMENT
AGREEMENT, ALL THOSE THINGS.
THEY ARE PRETTY WELL EDUCATED
THAT WAY ABOUT THAT. ONCE IN A
WHILE WE GET SOMETHING THAT
HAPPENS UNEXPECTEDLY, WE HAVE
PROCESSES IN PLACE IF WE NEED TO
USE THEM TO GET SOMETHING FILED
IF DISCLOSURE IS COMING. WE DO A
GOOD JOB OF KEEPING THEM
EDUCATED BECAUSE OF ONE ON ONE
TECH TRANSFER STAFF AND
LABORATORIES IS HUGE WAY THAT WE
ARE ABLE TO COMMUNICATE AND KEEP
UP TO DATE.
>>WE WILL MOVE FORWARD NOW. THE
NEXT PRESENTATION IS DR. DAVE
TUVESON WITH THE RAS WORKING
GROUP REPORT.
>>GOOD AFTERNOON, THANK YOU FOR
HAVING ME. I HAVE THE HONOR
SERVING AS THE EXTERNAL CHAIR OF
THE AD HOC COMMITTEE ADVISING
THE RAS PROGRAM AT FEDERAL
NATIONAL RESEARCH LABORATORY AND
NCI. RAS IS MOST COMMON CANCER
IN HUMAN CANCER AS MOST COMMON
ONCOGENE IN HUMAN CANCER AS YOU
KNOW, IT WAS DEEMED UNDRUGOR
DRUGGABLE BY OUR COMMUNITY AFTER
THE FAILURE OF TRANSFERASE
INHIBITORS AND HER ROWIC
EXPERIMENTS DONE BY MAJOR PHARMA
AND ACADEMIA. SO THOUGH NOT A
TRANSCRIPTION FACTOR PEOPLE
STAYED AWAY FROM IT. WHEN
HAROLD WAS NCI DIRECTOR THE
ADVISORS SUGGESTED IT MIGHT BE
TRACTABLE TO ORGANIZE OURSELVES
DIFFERENTLY SO WHICH LED TO THE
RAS INITIATIVE. IT STARTED IN
2013. THE GOAL TO MOBILIZE IN
ACADEMIC SECTOR PRIVATE SECTOR
GOVERNMENTAL SECTOR TO THINK
ABOUT THIS PROBLEM AND WORK
TOGETHER ON IT. TO DEVELOP WAYS
TO UNDERSTAND AND TARGET THESE
CANCERS AND HAVE RAS AS DRIVER
IN A DIFFERENT WAY. OPEN
RESEARCH MODEL COLLABORATIVE WAY
BETWEEN SECTORS KEEPING IN MIND
IP ISSUE YOU GUYS HAVE BEEN
DISCUSSING ELOQUENTLY AS I WAS
ARRIVING. THE IDEA WAS AT
FREDERICK YOU ARE ADVISORS AND
WHICH IS A STATE OF ART
FACILITY. THIS IS SERVED AS OUR
HOME FOR THIS INITIATIVE THE
PAST NINE YEARS. THE
COLLABORATING LABS. THE INITIAL
FUNDING CYCLE WAS A QUINTENIAL,
A FIVE YEAR APPLICATION, LEVI
WAS CHAIR FOR THE FIRST FIVE
YEARS. IT WAS REVIEW. IN 2017 IT
WAS RECOMMENDED TO GO FOR THE
SECOND COMPENDIUM OF FUNDING
WITH INCREASE FOCUS ON COUPLE OF
TANGIBLE TARGETS. FIRST FIVE
YEARS DERISKED IT,
PHILOSOPHICALLY AND EMOTIONALLY
THE LAST FIVE YEARS HAVE SHOWN
THAT WITH SERIOUS CONCENTRATED
ATTENTION THE ASPIRATIONAL GOALS
AND -- BECAME ACCOMPLISHMENTS.
THAT WAS A COMBINATION OF GREAT
STRUCTURAL BIOLOGY, BIOCHEMISTRY
BIOPHYSIC AND MEDICINAL
CHEMISTRY OF VARIOUS KINDS YOU
WILL HEAR ABOUT TODAY. SO IT
WAS RENEWED IN 2017 TO PUSH
AHEAD HARDER AND HERE WE ARE THE
NEXT FOUR YEARS. MY JOB IS
OUTSIDE ADVISOR TO JUST HAVE A
COMMITTEE OF APPROXIMATELY 12
PEOPLE THAT ADVISE MCCORMICK AND
NISSLEY AND COLLEAGUES, ANYTHING
FROM STRATEGIC STANDPOINT, COULD
BE TECHNICAL ADVICE, SCIENTIFIC
ADVICE, ANYTHING THAT STRETCHES
THEM AND MAKES THE WHOLE
INITIATIVE WORK MORE CLEARLY,
NEEDED TO ACCOMPLISH GOALS SO MY
JOB WAS TO SHOW UP TODAY AND
PRESENT THE RESULTS OF THE LAST
FOUR YEARS. THE OVERALL GOALS
FROM MY GROUP IS OVERSIGHT TO
FRANK AND DWIGHT AND TO BE
CANDID WITH THEM. ABOUT THINGS.
TO ENSURE THIS EFFORT WE HAVE
SPECIAL OPERATION EXISTING AT
FREDERICK IS MEETING SCIENTIFIC
OBJECTIVES INTERNALLY BUT ALSO
SOMETHING THAT RAISES THE BOATS
EXTERNALLY, ACADEMIC AND PRIVATE
SECTOR. WE HAD NINE MEETINGS
SINCE SEPTEMBER OF 18 UNTIL NOW.
SOME VIRTUAL, SOME IN PERSON.
HERE WE ARE LOOKING AT WHAT WE
ACCOMPLISHED OVER THE LAST FOUR
YEARS, MY JOB IS TO SUMMARIZE
THAT SUCCINCTLY. WE HAVE SEVERAL
THEMES FIRST TO LOOK AT RAS AS
SOMETHING THAT INFLUENCES CANCER
CELL BIOLOGY AND TO ASK FOR
THINGS ABOUT CANCER CELL BIOLOGY
TO INFORM WAYS TO COME UP WITH
NEW THERAPEUTIC WAYS TO GO AFTER
RAS. WHAT FRANK AND CO-WORKERS
WERE ABLE TO DO IS LOOK AT
PANELS OF CELL LINES. IN OUR
OWN LABORATORIES OR
COLLABORATORS, TO COME TO A
SENSE ON WHAT THE DIFFERENT RAS
MUTATIONS HAD IN TERMS OF
PROPERTIES AND PHENOTYPES AND
CELLS SO THEY HAD 66 PAPERS OVER
THESE LAST FOUR YEARS, SOME YOU
WILL HEAR ABOUT TODAY. THEY
CONFIRM METABOLISM WAS ALTERED
IN THE CELL LINES THAT EXPRESS
MUTANT RAS, VERSUS THOSE THAT
DID NOT, PARTICULARLY GLUTAMINE
METABOLISM AND REDOX METABOLISM,
THIS IS CORRELATE WITH
RESISTANCE ONCOLOGISTS USE IN
CLINIC. THEY WERE ABLE TO
CATALOG THE RAS MUTANT CELL
LINES IN SUCH A FASHION TO
BECOME A USEFUL INFORMATION
SOURCE FOR MULTIPLE RESEARCHERS
LIKE CURT HARRIS FOR P53 AND
CANCER RESEARCH IN 1994. THEY
FOUND SOME R ACTIONS MUTANTS NOT
CODON 12 MUTATIONS BUT OTHER
CODONS, AND INCREASE GTPASE I
WAS COMPARED TO G 12D PROTEIN. I
ASSUME Y'ALL ARE GREAT
BIOCHEMISTS SO I WILL GIVE YOU A
PRIMER. WHEN YOU HAVE A MUTATION
IN CODON 12, THE MOST COMMON MY
TUITIONNA R AXS HUMAN CANCER IT
SLOWS DOWN THE ENZYME, YOU HAVE
A HYPO ACTIVE PROTEIN. THE
THINKING IS THAT PROTEIN CAUSES
CHANGES IN CELL THAT CREATED
TRANSFORMING PROPERTY IS A DRUG
WOULD SPEED UP THAT PROTEIN OR
REMOVE PROTEIN FROM CELL. WE
FOUND SOME RAS ONCOGENES HAD
FASTER GTPASE ACTIVITY THAN WILD
FACTOR. SO SUGGESTING WE NEED A
DIFFERENCE TYPE OF DRUG FOR THAT
ALLELE. THAT IS UNCOMMON ALLELE
BUT ONE OF THEIR FINDINGS. WE
HAVE DONE COOL BIOPHYSICS AND
ONE IS TOP DOWN MASS
SPECTROMETRY. Y'ALL KNOW WHAT
MASS SPEC IS, YOU IDENTIFY
THINGS IN A MIX, USUALLY A
PEPTIDE OR SMALL MOLECULE. YOU
CAN ACTUALLY NOT FRAGMENT THE
MOLECULES FIRST AND DO -- INDUCE
A DIFFERENT FORM OF MASS SPEC
THAT I ALLOWS YOU TO SEE
ISOFORMS OF PROTEINS THAT MORE
OR LESS DIFFER DUE TO POST
TRANSLATIONAL MODIFICATION. THAT
IS APPLIED HERE AT FREDERICK AND
THEY HAVE EXCITING DATA ABOUT
DIFFERENT POPULATIONS OF RAS YOU
FIND IN DIFFERENT CANCER CELLS,
THIS TELLS US ABOUT POST
TRANSLATIONAL MODIFICATION AND
ENZYMES WHICH MAY CAUSE THAT.
LAST THING THEY DEVELOPED
SYNTHETIC MEMBRANES IN THEIR
SHOP AT FREDERICK TO TELL US
THINGS WHAT ARE THE LIPID
CONSTITUENTS NEEDED TO ASSEMBLE
THE RAS SIGNALING COMPLEX.
PRESENT RATESSED GOES TO
SURFACE. OTHER PROTEINS ARE
INVOLVED IN THAT. THAT'S SEEN BY
EFFECTOR PROTEINS HOW THAT
HAPPENED CHANGE HOW WE CREATE
POTENTIAL DRUGS. THAT LAST WAS
PUBLISHED NICELY RECENTLY. THE
MODERN WAY TO MAKE MEDICINE WITH
GREAT STRUCTURAL BIOLOGY. HIGH
THROUGH PUT CRYSTALLOGRAPHY IS
HOW PHARMACEUTICAL COMPANIES ARE
RELIANT THESE DAYS. YOU CAN DO
NMR BASED ET CETERA BUT HIGH
THROUGH PUT CRYSTALLOGRAPHY IS
GREAT. THIS GROUP IS PROBABLY
WORLD LEADING IN STRUCTURAL
DETERMINATION WILD TYPE MUTANT
RAS. I SAY THAT WITH CONFIDENCE,
THEY ARE PROBABLY THE BEST ON
THE PLANET. SO THEY HAVE GREAT
CRYSTALLOGRAPHY AND NOW CRYOEM
AS WAY TO LOOK AT VAGUE ISSUES
HOW MANY PROTEINS BUT NOT THE
TONIC RESOLUTION. THEY HAVE
TONIC RESOLUTION FOR WHY WOULD
TYPE AND RAS. THEY HAVE DONE
THAT FOR MANY HITS MADE
CHEMICALLY. AND THAT IS I THINK
ALSO ELEVATED THE IMPORTANCE AND
PROMINENCE OF PROGRAM SO THE
FIRST TO GET A STRUCTURE OF THE
RAS BINDING DOMAIN, CRAF IS THE
EFFECT TORR DOWNSTREAM OF MUTANT
RAS AND CRD, ANOTHER PROTEIN
DOMAIN ON RAF. BOUND TO WILD
TYPE AND MUTANT AND THEY
PUBLISPUBLISPUBLISHED IN NAY CO.
THAT CHANGED THE WAY PEOPLE
THOUGHT ABOUT SURFACE CONTACT
BETWEEN RAP AND RAS WITH GTP
THAT INFORMS CHEMISTS HOW TO
UNITE SMALL MOLECULES WHICH MAY
FIT TO BLOCK THAT INTERACTION OR
DO THE OPPOSITE TO BRING IT MORE
STRONGLY TO SO CALLED GLUE THEM.
USING THE GLUE VERSUS BREAK
METHOD THE .3 HERE THEY DEVELOP
FIRST IN CLASS BLOCKERS TO PI 3
KINASE ALPHA AND MASS GTP. PI 3
KINASE IS ESSENTIAL PATHWAY IN
ALL CELLS AND MET SOW WANTS WAN
SOMETIMES MY TAINTED IN CANCER
AND RAS MUTANT CELLS DRIVE IT IS
PATHWAY DIFFERENT THAN THE
KINASE CASCADE BUT PI 3 KINASE
IN GENERAL IS HARD FOR MEDICAL
ONCOLOGISTS TO DEVELOP BECAUSE
IT CAUSE HYPERGLYCEMIA AND OTHER
THINGS. THESE FOLKS BECAUSE THEY
CAN CRYSTALLIZE WITH RAS GTP
FIGURE A SMALL MOLECULE THAT
GLUEING TO AND CHEMIST USE THEIR
AX TO BREAK IT INDO A BLOCKER
COMPOUND THAT BINDS PI 3 KINASE
ALPHA PREVENTING FROM RAS GTP.
FIRST IN CLASS FIRST DESCRIBED,
COMPOUND. THEY HAVE TONS OF
CRYSTAL STRUCTURE, LOOKING AT
THAT COMPOUND AND BIOLOGY. LAST
IS NEUROFIBROMINUTE. THIS IS THE
GENE RESPONSIBLE WHEN MUTATED
FOR NEUROFIBROMATOSITOSIS. INHED
CANCER PRE-DISPOSITION SYNDROME
BECAUSE BECAUSE THEY ARE GREAT
AT CRYSTALLOGRAPHY, THEY WERE
THE FIRST THE PUBLISH THIS WORKS
AS A DIMER. THIS IS ESSENTIAL IF
THINKING ABOUT DRUGS THAT TETHER
NF 1 TO MUTANT RAS, ONE OF THE
NEXT IDEAS THEY HAVE. NEXT
SLIDE. SO THEY HAVE LOOKED A T
RAS CELL LINES, RAS CRYSTAL
STRUCTURE, THEY HAVE DONE
SOMETHING MORE SOPHISTICATED
FROM MOLECULAR STANDPOINT BY
LOOKING HOW RAS WORKS IN THE
MEMBRANE USING FANCY MICROSCOPES
BUT ALSO SUPER COMPUTERS AND
MACHINE LEARNING. ARTIFICIAL
INTELLIGENCE METHODS. BY USE
EMPIRIC METHODS THEY WERE ABLE
TO SHOW THREE STRUCTURE THAT RAS
HAD ON THE MEMBRANE WHEN BOUND
-- WHEN PRESENT AND WHEN BOUND
TO GTP THAT CHANGES THE
POPULATION STATES OF THE THREE.
ONE OR TWO ARE NEXT TO MEMBRANE.
THESE ARE LATENT STRUCTURE AND
CAN'T BIND TO MAP KINASE CASCADE
LIKE RAF. ONLY IN CYTOPLASM
THAT ALLOWS ACCESS TO THE RAF
MOLECULE. THE REASON THOSE
DETAILS ARE RELEVANT IS IF
CREATING A COMPOUND THAT BLOCKS
RA,F YOU DON'T WANT TO CREATE
ONE THAT NEVER BINDS TO PART
THAT IS IRRELEVANT FOR RAF SO
THEY KNOW EXACTLY THE PART OF
RAS GTP THAT STICKS IN THE
CYTOPLASM, THAT IS WHERE THEY
ARE FOCUSED. SECOND THEY USE
MOLECULAR DYNAMIC STIMULATION AS
WELL AS DIRECT MEASUREMENTS,
PLASMA RESONANCE TO PREDICT HOW
THESE THREE CONFIRMATIONS OF RAS
GO BACK AND FORTH AND WHICH
COMPLEXES, WHICH FORM OF RAS IS
RELEVANT IN CANCER CELLS VERSUS
NORMAL CELLS. UNDERSTANDING WHAT
IS IN THE DETAILS OF PLASMA
MEMBRANE IS ESSENTIAL. LAST
THING, THEY HAVE THIS ALCOHOL
PROJECT WORKING WITH ANOTHER
GOVERNMENTAL AGENCY. THE
DEPARTMENT OF ENERG ENERGY. WHEE
LAWRENCE LIVERPOOL NATIONAL LAB
HAS A SUPER COMPUTER AND THIS
MACHINE LEARNING BASED APPROACH
WHERE THEY FEED IN SIMULATIONS
OF DATA FROM PROJECTS ONE AND
TWO AND COME UP WITH ESSENTIALLY
A DYNAMIC ASSESSMENT HOW RAS
MOVES BACK AND FORTH TO ENGAGE
EFFECTORS AS YOU ALER
CONSTITUENTS MANY THE PLASMA
MEMBRANE. WITH THIS SUPER
COMPUTER APPROACH THEY ARE
HYPOTHESIZING ADDITIONAL
CONFIRMATIONS TO THINK ABOUT
FROM DRUG DISCOVERY STANDPOINT.
THIS IS THE FIRST TIME LNL HAS
WORKED WITH THE FREDERICK
NATIONAL CANCER RESEARCH
LABORATORY TO DO ANYTHING ON
THIS SCALE, USUAL WILL I LOOKING
AT STARS IN THE SKY AND OTHER
THINGS RELEVANT TO DEFENSE. SO
WITH THIS IS THE BACKGROUND,
WHICH I HAVE CHEMISTRY, GOOD
CHEMISTRY. I HAVE THE GOOD
FORTUNE OF WORKING IN ENGLAND
SIX YEARS, GOT TO SEE HOW THE
ICR WAS SET UP SOUTH OF LONDON,
THEY HAVE INTERNAL CHEMISTRY
PROGRAM. 25 TO 30 CHEMISTS THEY
INVENTED DRUGS LIKE TAMAZOLAMIDE
AND THEY HAD A GOOD INVESTMENT
MODEL FOR FINANCIAL SO A THIRD
OF BUDGET CAME FROM PATENTS. SO
THESE NOW HAVE A CHANCE AT THAT
TOO BECAUSE THEY HAVE A LEAD G
12C INHIBITOR, BETTER THAN AMJEN
AND COMPOUND FDA APPROVED TO
TREAT LUNG CANCER BECAUSE IT
HITS BOTH RAS ON AND THE RAS OFF
STATE. SEEMS BETTER IN VITRO
AND MUCH BETTER IN VIVO BY
ASSESSMENTS TAKEN. YOU CAN SAY
DO WE REALLY NEED ANOTHER G 12C
INHIBITOR? READ THE PAPERS IN
NEW ENGLAND JOURNAL AND
ELSEWHERE. PATIENTS ARE
RESPONDINGTANT SUBSEQUENTLY,
COME BACK WITH RHESUS TAN
DISEASE. IF THEY HAVE A BETTER
DRUG WHICH WILL HAVE MORE
DURABILITY, IN THE PATIENT THAN
THIS COULD BE BIG DEAL. OF
COURSE G 12C IS A RARE ALLELE
WHEN YOU THINK OF PANCREAS
CANCER AND COLON CANCER. FOR
THAT THEY HAVE A WHOLE PIPELINE
OF MOLECULES THEY THINK WILL
WORK IN ASPARTAT MUTANT AND
AVAILING MUTANT NOT READY FOR
CLINIC. SO THEY HAVE A COMPOUND
THEY CREATED WITH PARTNERSHIPS
WITH PHARMA. AS I SAID BEFORE
SEEMS BEAR THAN ANYTHING OUT
THERE. THINK IT WILL GO CLINIC
FIRST QUARTER OF THIS NEXT YEAR
SECOND POINT HERE THEY HAVE THE
FIRST PI 3 KINASE ALPHA BLOCKER
MOLECULE, FIRST I HAVE HEARD OF,
NOTHING IN THE THE LITERATURE IF
YOU PUBMED AND LOOKS LIKE THIS
COULD BE A SMART WAY TO BLOCK A
PATHWAY IN RAS MUTANT CELLS.
WILL THIS TURN OUT REALLY
IMPORTANT CLINICALLY? BEHAVE TO
SEE BUT THIS IS IMPORTANT FROM A
SCIENTIFIC STAND POINT WHETHER
IT IS IMPORTANT FROM CLINICAL OR
FINANCIAL STANDPOINT I WOULD SAY
STILL HAVE TO BE FIGURED OUT.
THEY HAVE THOSE OTHER MUTANT
ALLELES THAT I HAVE TALKED
ABOUT, SPARTATE ALLEL ALLELE. TY
HAVE WAYS OF NOT JUST GOING
AFTER CYSTEINE BUT OTHER AMINO
ACIDS WHICH EXIST IN RAS. THEY
HAVE ONE METHOD MAKES A GOOD
PROTAC. A METHOD INVENTED BY
CRAIG CRUISE AT YALE WHICH SMALL
MOLECULE UBIQUITIN LIGASE THAT
GOES TO PROTOSEWSOME SO THEY
HAVE A COUPLE THAT GOES THROUGH
PROTAC. AND THEY HAVE -- NEXT
SLIDE PLEASE. WHAT ABOUT
SCIENTIFIC COMMUNITY? WHEN THIS
STARTED, TECH YEARS AGO, MORE
THAN THAT, WHEN THE IDEA TO TRY
THIS I REMEMBER SHOULD WE GO
AFTER? NO. DUMB IDEA, PAPER IN
NATURE HE COULD DO IT FROM USCF
STAND POINT, A TOOL COMPOUND
METHOD BUT WE HAD DECIDED BEFORE
THEN I THINK THAT COULD BE
CORRECTED HOLD BY DOUG WHO HAS
BACK STORY BUT COMMUNITY THOUGHT
IT WAS NOT A SMART THING,
UNDRUGGABLE TARGET SO BRINGING
THE COMMUNITY ALONG IS A -- HAS
BEEN A GOAL AND THEY HAVE DONE A
GREAT JOB EMBRACING THE
IMMUNITY, VERY OPEN WITH ALL THE
THINGS THEY INVENTED. BEST
PLACE TO CRYSTALLIZE RAS THEY
HAD TO CREATE THE PROTEIN, DO IT
WITH APRESENT RATION ON IT.
DEVELOP ALL THE TOOLS AND
PLASMIDS TO CLONE THE GENES ALL
THE CELLS, MICROBIAL OR EUKAR
EUKARYOTIC TO PRODUCE PROTEIN
PURIFY PROTEIN CRYSTALLIZE, ALL
THAT, THEY INVITED THE COMMUNITY
TO COME TO SHOP TO LEARN THIS
STUFF. MULTIPLE TIMES. THE DEAL
WITH PHARMA IS DIFFERENT, THEY
HAD THE ENCOURAGE PHARMA TO GET
INTO SPACE. PHARMA IS NOR THAN
IN THE SPACE NOW. THE LAST FOUR
YEARS PUBLISHED 66 PAPERS AND IT
IS TOTALLY DERISKED AT THIS
POINT. EVERYONE BELIEVES
DRUGGABLE. THE QUESTION IS WILL
IT MATTER. THAT'S COMING TO THE
WHY THE PROGRAM IS IMPORTANT FOR
YOU TO CONSIDER KEEP IT GOING.
I ALREADY SAID, THEY HAVE GIVEN
1,200,000 PLASMIDS ALL THESE
PROTEINS AND CELL LINES DOING
BETTER THAN ADD GENE OR ATCC.
THEY RANK WITH OTHER TWO SOURCES
FOR THINGS. THEY SPONSORED
MULTIPLE INTELLECTUAL ENCOUNTERS
FOR PEOPLE, THEY HOST SYMPOSIA
IN FREDERICK. DONE IT EVERY
YEAR, EVERY OTHER YEAR AND THEY
HAVE BEEN TERRIFIC. MANY OF YOU
HAVE COME TO THEM AND THERE IS
ONE MANY A FEW WEEKS, OR NEXT
WEEK, I HOPE SOME ARE GOING TO
THAT. THEY HAVE DONE THE SOCIAL
MEDIA THING. WE HAVE A WEBSITE,
PEOPLE PUT THEIR TESTIMONIAL UP
ABOUT NEW STUFF THEY ARE
DISCOVERING AND IT'S BECOME LIKE
I DON'T KNOW LIKE INFORMATION
STREAM. EVERYONE THINKS ABOUT
RAS AS SOMETHING THAT CAN BE
DONE AND THEREFORE THEY ARE LESS
SCARED ABOUT OTHER TARGETS TOO.
RAS HAS BROKEN THE GLASS
CEILING. NEXT SLIDE PLEASE.
WHICH WOULD BE/THIS MUST BE THE
LAST SLIDE. FROM MY STANDPOINT
IS THE UNPAID ACADEMIC
INTERESTED ADVISOR BECAUSE I
STUDY PANCREAS CANCER. I THINK
THEY HAVE -- THEY HAVE BEEN
AMAZING. THEY HAVE GONE PAST
THEIR OBJECTIVES THEY HAD TEN
YEARS AGO DESPITE THE PANDEMIC
WE HAVE DEALT WITH. THEY HAVE
TWO MOLECULES HEADED TOWARDS
IND. ONE HITS BOTH ON AND OFF
STATE. I HOPE IT BLOWS THE TWO
FDA APPROVED OUT OF THE WATER,
WE HAVE I'LL HAVE TO SEE. THEY
HAVE THIS COMPLEX BREAKER WHICH
IS FIRST IN CLASS AND GOING TO
ENCOURAGE PHARMA TO MAKE THESE
TWO, FOR DIFFERENT APPROXIMATE
MR. AQUATIONS. THEY PROBABLY
HAVE AGAIN THE BEST PLACE TO
STUDY RAS FROM THE STANDPOINT OF
I HAVE A MUTATION WHAT IS
PROTEIN LOOK LIKE, WHAT IS THE
STRUCTURE, WHAT DOES IT DO
BIOCHEMICALLY. THEY BROADEN TO
EFFECTOR BE THEY NEGATIVE OR
POSITIVE REGULATORS OF R ASHS.
THEY PUBLISH PAPERS ON
BIOCHEMISTRY AND REGULATION.
THAT IS A REALLY IMPORTANT
FINDING. THEY HAVE THIS
BIOPHYSICS ARM TO THEM AND
MACHINE LEARNING COMPUTATIONAL
ARM WHICH TELLS SOMETHING HOW
THESE MOLECULES EXIST ON CELLS
WHICH ARE REQUIRED FOR LIFE,
CIRCUMVENTED BY CANCER TO MODIFY
SIGNALING PATHWAYS DOWNSTREAM.
THAT MIGHT BE MY LAST SLIDE.
CLICK IT TO TELL ME. SO I HAVE
RECOMMENDATIONS. MY
RECOMMENDATION AFTER THINKING
ABOUT AND TALKING TO THEM AND TO
MY GROUP, WE ARE FOUGHT QUITE
DONE. WHEN I THOUGHT SIX, 12
MONTHS AGO, I SAID PROBABLY THE
PROOF IS DONE MAYBE PHARMA WILL
DO THE RESTFUL DOUBT THAT IS THE
CASE. PHARMA IS WAY TOO
SHORTSIGHTED, THEY PROVED THAT
OVER AND OVER. I THINK HAVING A
SPECIAL OPS PROGRAM LIKE THIS IN
INSIDE MEANS WE THINK, IT MEANS
WE ARE NOT A REFLEX, WE HAVE A
BRAIN. SO IT IS IMPORTANT FOR US
TO KEEP GOING FOR VARIETY OF
REASONS. I THINK THIS INHIBITOR
THEY HAVE VERY EXCITED ABOUT THE
COMPOUND IS TOTALLY UNIQUE SO IT
SHOULD GET PROTECTED BY LAWYERS
AND GET INTO CLINIC. ONCE
THROUGH THE VARIOUS SMALL AND
MEDIUM SIZE ANIMALS. IT WILL
TURN OUT TO BE GREAT MAYBE AND
HAVE RETURN ON INVESTMENT. IF
YOU SET UP THE RIGHT WAY. FOR
THE PROGRAM. RESISTANCE TO RAS
INHIBITORS. THE G 12 INHIBITORS
ARE GREAT, SIX MONTHS LATER
DON'T. SO GLEVAC WITH -- DOESN'T
WORK. IT WORKS GREAT IN EARLY
CML, THAT IS TRUE OF A LOT OF
THINGS. SO I THINK THESE ARE
ABOUT RESISTANCE BECAUSE WE TELL
THEM, IT IS IMPORTANT THEY DO SO
BECAUSE SOME IS ON TARGET
RESISTANCE WHICH THEY ARE GREAT
AT. SOME IS OFF TARGET
RESISTANCE THEY HAVE TO KEEP
THAT COORDINATED ENVIRONMENT
COMMUNITY GOING THEY HAVE
BECAUSE THAT IS NEW TARGETS TO
TAKE ON BOARD. ONE RESISTANCE
PATHWAY IS MIC. THEY MIGHT HAVE
TO BECAUSE IT IS LIKELY ONE OF
THE MOST IMPORTANT RESISTANCE
PATHWAYS IN RAS MUTANT CANCER
AND YOU CAN SAY MIC IS IMPORTANT
FOR OTHER CANCERS TOO. I DON'T
KNOW THE BANDWIDTH TO DO IT WITH
PEOPLE NOW BUT THAT IS SOMETHING
AS COMMUNITY AS THINK TANK WE
SHOULD CONSIDER. SECOND BULLET
POINT. THEIR OTHER TARGETS PI 3
KINASE ALPHA COMPLEX COULD BE
TERRIFIC AND THAT MAY WORK IN
NON-RAS CANCERS TOO. NON-RAS
MUTANT CANCER. THIRD POINT,
THERE IS THE RENAISSANCE, OTHER
PEOPLE, HAVE BEEN RESPONSIBLE
FOR SHEPHERDING THE RENAISSANCE
THANKS TO DOUG FOR STAYING
PATIENT WITH THE PROGRAM,
HOPEFULLY MONICA AND NEW JOB
ISN'T TRYING TO CUT CORNERS WITH
THE BAD COMMITTEE. BECAUSE WE
ARE IN A GOOD SPOT OUR PATIENTS
NEED BETTER MEDICINE. THIS
PROGRAM IS GIVING US PART OF
THAT FIRST TIME REAL MEDICINE
FOR CANCER THAT ARE TOTALLY
TREATABLE. WE HAVE A COMMUNITY
OF PRIVATE AND PUBLIC AN
GOVERNMENT, YOU HAVE TO BRING
THE FDA BECAUSE YOU HAVE TO FILE
INDs AND THAT STUFF. I THINK
YOU DON'T WANT TO DISRUPT THE
BAND NOW BECAUSE OF METHOD FOR
BIOPHYSIC AND -- THAT'S
IMPORTANT AS WE FIGURE HOW TO
TREAT PATIENTS. THEY SHOULD BE
ALLOWED TO GO AFTER ADDITIONAL
RAS FAMILY MEMBERS AROUND IF WE
ASK HEM TO WORK ON RESISTANCE
THEY NEED MORE RESOURCES MAYBE
THAT IS NOT WHAT YOU WANT TO
HEAR, MAYBE YOU WANT TO HEAR
MORE FROM LESS, AS FROM THE
OUTSIDE THESE PEOPLE HAVE DONE
BETTER WORK THAN ANY THAT I KNOW
IN THE CANCER SPACE, AS A
COLLECTIVE COMMUNITY OPPOSED TO
THE INDIVIDUAL DISCOVERIES THAT
MADE THESE BREAKTHROUGHS FLOUT
THROUGHOUT. THERE'S NO WAY THEY
COULD HAVE DONE THIS WITHOUT
VILLAGE TYPE APPROACH. I'M DONE
WITH MY SOAP BOX. I SUCKED UP A
LOT OF OXYGEN GIVING YOU ONLY
SIX MINUTES FOR QUESTIONS. IF
YOU WANT TO, GO AHEAD.
>>GREAT REPORT. YOUR ENTHUSIASM
IS INFECTIOUS. COMMEND ON YOUR
REPORT.
>>I GOT ONE. THANK YOU SO UP
MANY DAVID, GOOD TO SEE YOU. IF
YOU WERE ME WHAT IS THE BIGGEST
WORRY? BESIDES FINDING THE MONEY
BUT WHAT IS YOUR BIGGEST CONCERN
IF YOU WERE SITTING IN MY CHAIR?
>>MY BIGGEST CONCERN RIGHT NOW,
IF I WERE ABLE TO SLIGHTLY DO
WHAT YOU ARE ASKING, WOULD BE TO
SAY BEST IN CLASS. AS OF RIGHT
NOW COMPARED TO TEN YEARS AGO
INVESTMENT IN RAS FROM BIOPHARMA
HAS TO BE THOUSAND TIMES BIGGER
THAN THEN. YOU HAVE TWO
BLOCKBUSTER DRUGS AND SO THERE
ARE INDEED BUDGET FOR RAS STUFF
HAS TO BE WHATEVER AND EVERYBODY
ELSE HAS RAS PROGRAM. THE
INVESTMENT BY THE PRIVATE
EXTRAMURAL COMMUNITY IS HUGE SO
YOU HAVE TO ASK WHAT THEY HAVE
RIGHT NOW THAT I DESCRIBE AS
BEST IN CLASS, IS IT REALLY BEST
IN CLASS? I WOULD THINK THAT YOU
RECALL APPROACH TO FIGURING OUT
IN CLEVER THEY HAVE IS POSSIBLY
BEST IN CLASS BUT THAT IS WHERE
YOU ASSEMBLE GROUP OF PEOPLE
PRIEST AND OUTSIDE AND THAT
SHOULD BE THE TASK ARE THEY BEST
IN CLASS, IF SO HOW TO PROTECT
SO COMPANY DOESN'T BUY HEM IN
LOT AND THEY LEAVE. SO I DON'T
KNOW THE ANSWER TO THAT EITHER.
I HAVEN'T REALLY TOTAL YOU, I
MEAN I RETENTION IS A HUGE ISSUE
IF THEY ARE BEST THAT CLASS. THE
MAIN WAY TO MAINTAIN THEM IS
MAKING SURE EGOS ARE MASSAGED.
YOU HAVE TO DO MIC 2, THEY CAN
DO BLOODY EVERYTHING THAT ANYONE
SHOULD HAVE TO DO IF THEY ARE
GOING AFTER INTRACTABLE DRUG
TARGET.
>>SO WE HAVE COUPLE OF
QUESTIONS. FIRST MARY. THEN
RODNEY.
>>THANK YOU, WE LEARNED A LOT.
GREAT PROGRESS. WONDERING WHEN
YOU THINK OF THE UNIQUENESS OF
NCI FREDERICK LABSES AND WE
HEARD THOSE INCREDIBLE PDX
MODELS, IS THERE ANY INTEREST IN
CREATING SPECIFIC RAS PDX MODELS
NO ONE ELSE HAS?
>>GOOD QUESTI QUESTION. THAT CD
EASILY BE DONE. I DON'T KNOW YOU
CAN DO IT AS A PDX OR AS A
GENETICALLY ENGINEERED MOUSE. IT
SEEMS THE IMMUNE RESPONSE IS
RELEVANT IN HUMAN AND MOUSE
RESPONSE TO ON TARGET THERAPIES
IF YOU DO PDX IN GENERAL YOU
DONE HAVE NK CELLS EITHER. I
KNOW PDXs DO EXIST TODAY AND
TESTING THEM ON THEM. THAT IS
NOT HARD. IF THEY DON'T HAVE, MY
LAB CAN GIVE WHATEVER THEY NEED
TO SET UP DIFFERENCE ALLELES AS
COULD HANDFUL OF MY COLLEAGUES.
THAT IS WHAT JIM PUT TOGETHER.
ME HAS GREAT COLLECTIONS AND
DOES HAVE MOST ALLELES IN PDX
FORM OR ORGANOID FORM AND YOU
CAN MAKE A PDX FROM ORGANOID
TRIVIALLY. ED FROM
>>THIS IS VERY INFECTIOUS.
CLEARLY YOU HAVE TO TAKE THIS IF
POSSIBLE WHAT IS POSSIBLE WITH
THE GROWTH OF TESTIFY TECHNOLOGY
OVER TIME. AND TOOLS INTEGRATING
EVERYTHING. THAT WE CAN USE TO
BUILD PROGRAM. SECOND THING,
THE TAGGABLE 2 COMPOUNDS GOING
-- THEY ARE RESISTANT. IT WOULD
BE IMPORTANT TO THINK ABOUT LONG
TERM IF YOU WANT TO COMPETE.
FIRST IN CLASS, DRUG
COMBINATIONS IF IT IS ORAL IT IS
LONG TERM TREATMENT, THAT IS
WHAT WE ARE THINKING CONSTANTLY
ABOUT. TARGETING. COMBINATIONS
TO PROVIDE THOROUGH RESPONSE. SO
YOU CANNOT COMPETE WITH THE
LARGE COMPANY, GOB TO POUR MONEY
IN THE CLINICAL PROGRAM SO WE
ARE GOING TO BE WAY BEHIND ALL
THE TIME. SO WHAT WE CAN COMPETE
IS TO DEMONSTRATE PRINCIPLE.
EVERYONE IS GOING AFTER DRUG
COMBINATIONS. SO QUESTION IS
THAT WHEN SHOULD FREDERICK BE
INVESTING AHEAD OF THE GAME
WHERE WE ARE GOOD AT
INTELLECTUAL THINKING, WAY AHEAD
OF TIME.
>>THIS IS A REALLY O --
>>THAT IS WHAT I WOULD --
>>THANK YOU. GREAT QUESTION. SO
WHEN THE FIRST AKT PLUS MEC
COMBINATION WAS DEVELOPED, AND
PUT INTO PATIENTS, THE HOPE WAS
IT WOULD HANDLE THE RAS CANCER.
I HOPE YOU KNOW THE SORRY WHAT
HAPPENED. PATIENTS WERE SICK.
BECAUSE THOSE TWO COMPOUNDS IN
HUMAN, CAUSES SKIN TOXICITY
WHICH PREVENTED DOCTORS FROM
DOSING MEDICINE SO YOU CAN HIT
THE CANCER. THEY NOW HAVE PI 3
KINASE ALPHA BLOCKER SO THEY DO
HAVE A COMPETITIVE ADVANTAGE AS
FAR AS I KNOW NOBODY HAS. IF
THEY ARE RIGHT THE PI 3 KINASE
ALPHA DRUG COOPERATE WITH MAP
KINASE INHIBITORS, THAT COULD BE
SOMEBODY'S ERK INHIBITOR THEY
HAVE A COMPETITIVE ADVANTAGE
ALREAALREADY. THIS IS SOMETHINGO
MONICA, YOU SHOULD USE YOUR
CLINIC AT THE NCI TO TEST THESE
PHASE 1 COMBINATION, DO IT
YOURSELF. DO THE FIRST STUDY AT
THE NCI. TEST THE PI 3 KINASE
ALPHA WITH MEK INHIBITOR AND
BECAUSE RODNEY IS RIGHT. IN THE
END OF THE DAY THE LAST THING IS
A ME TOO OPERATION, YOU ARE
PUTTING 50 MILLION BUCKS INTO
BECAUSE YOU COULD FUND I DON'T
KNOW HOW MANY RO1s. A LOT SO I
HI THIS QUESTION IF COMPETITIVE
LANDSCAPE ARE THEY STILL AFTER
INTRACTABLE PROBLEM OR JUST
COLOR NOW THAT IT IS NOT
INTRACTABLE? I THINK THEY HAVE
INFRASTRUCTURE AND THIS GROUP
ABLE TO SOLVE PROBLEMS BETTER
THAN INDUSTRY RIGHT NOW SO
PRINCIPLE THEY CAN GENERATE NEW
MOLECULES NEW IP. HOOK IT UP TO
CLINIC. THAT'S WHAT COMPANIES
DON'T HAVE. USE YOUR CLINI CLIN.
(OVERLAPPING SPEAKERS)
>>WE NEED TO MOVE ON. IN THE
INTEREST OF TIME. WE NEED A
MOTION TO APPROVE THE WORKING
GROUP PLAN. WORKING GROUP
REPORT. DO I HAVE A MOTION?
LISA. SECOND, JOHN. ALL THOSE IN
FAVOR. ANY OPPOSED? ANY OTHER
DISCUSSION? GREAT. THANK YOU,
DAVE. GREAT JOB. SO WE ARE NOW
MOVING TO ONGOING AND NEW
BUSINEBUSINESS. DR. CANE WILL GA
BRIEF PRESENTATION ON THE
ESTABLISHMENT OF A NEW FNLAC
WORKING GROUP TO EVALUATE THE
RAS PROGRAM. THE NEW PROPOSED
NAME IS NCI RAS INITIATIVE
EVALUATION TEAM AD HOC WORKING
GROUP. AFTER THIS PRESENTATION
WE NEED A MOTION TO APPROVE
THIS. SO PLEASE. DR. CANE. --
DR. KANE.
>>THANK YOU, GOOD AFTERNOON,
THANK YOU FOR THE INVITATION TO
JOIN YOU TODAY. IN WAY OF
INTRODUCTION MY NAME IS CHRIS
KANE, PROGRAM OFFICER IN THE
OFFICE OF SCIENTIFIC OPERATIONS
WITH THE NCI FREDERICK. I'M ALSO
THE CONTRACTING OFFICER
REPRESENTATIVE FOR THE NCI RAS
INITIATIVE. IT IS MY PLEASURE TO
PRESENT THIS BRIEF PRESENTATION
ENTITLED ESTABLISHMENT OF
WORKING GROUP TO EVALUATE NCI
RAS INITIATIVE. I WOULD LIKE TO
BEGIN TOUCHING VISION AND
HISTORY OF THE RAS INITIATIVE.
AS DR. TUVESON ELOQUENTLY STATED
THE VISION AND OVERARCHING GOAL
IS MOBILIZE THE ENTIRE CANCER
RESEARCH COMMUNITY TO DEVELOP
WAYS TO UNDERSTAND TARGET CANCER
DRIVEN BY MUTANT KRAS. USING
THIS UNIQUE OPEN RESEARCH MODEL
WITH COLLABORATION ACROSS
GOVERNMENT, ACADEMIA, AND
INDUSTRY. SO THE RAS INITIATIVE
DEVELOPED AND ESTABLISHD IN 2013
AND ADDRESSED CRITICAL KNOWLEDGE
GAPS THAT IMPEDED RAS AS DRUG
TARGET FOR DECADES. THEY WERE
SUCCESSFUL AND PROVIDING GREATER
INSIGHT TO RAS BIOLOGY SOLVING
MULTIPLE PROTEIN STRUCTURE AND
PROVIDING IMPRESSIVE AMOUNT OF
REAGENTS TO THE OVERALL RAS
RESEARCH COMMUNITY. IN 2017,
THE RAS INITIATIVE WAS REVIEWED
AND RENEWED FOR ANOTHER PERIOD
OF PERFORMANCE WITH INCREASE
FOCUS ON ADVANCING RAS
THERAPEUTIC COMPOUNDS AND
PROVIDING INCREASINGLY
SOPHISTICATED BIOPHYSICAL MODEL
FOR RAS ACTIVATION SIGNALING.
WHICH BRINGS US TO TODAY. NCI
RAS INITIATIVE RESEARCH TEAM IS
SEEKING ADDITIONAL FIVE YEAR
PERIOD OF RENEWAL. WITH THE
EXPRESS GOALS OF PUSHING
VALUABLE NEW PRE-CLINICAL AND
CLINICAL DRUG CANDIDATES INTO
CLINICAL EVALUATION AND
BROADENING THE RAS DIRECTED
THERAPEUTICS TO ADDITIONAL
ALLELESK EFFECTOR PROTEINS AND
OTHER INNOVATIVE STRATEGIES SO
THE RENEWAL PROCESS REQUIRES
ESTABLISHMENT OF A U WORKING
GROUP. IN ORDER THE JUDGE
SCIENTIFIC MERIT PRODUCTIVITY
INNOVATION OF THE RAS
INITIATIVE, THE FNLAC WILL
CONVENE A NEW INDEPENDENT AD HOC
RAS INITIATIVE EVALUATION TEAM
WORKING GROUP TO CONDUCT REVIEW
OF RENEWAL PACKAGE.
THAT WILL CONSIST OF COMPONENTS,
FIRST IS REPORT AND
RECOMMENDATIONS OF THE EXISTING
FNL RAS AD HOC WORKING GROUP
JUST ENDORSED. ALSO INCLUDE A
FULL WRITTEN PROPOSAL BY THE
RESEARCH TEAM AND AS WELL AS IN
PERSON SESSION TO EXPLAIN
PROPOSAL IN GREATER DETAIL. .
WHICH THEY WERE HIGHLIGHT
PROGRESS TEAM MADE DURING THE
CURRENT PERIOD OF PERFORMANCE TO
DESCRIBE ENGAGEMENT WITH
EXTRAMURAL RAS COMMUNITY. AND
PROPOSEDDED FEATURE RESEARCH AND
DEVELOPMENT PLANS. SO THE REMAKE
OF THE WORKING GROUP IS ON THE
NEXT SLIDE. SO THE REMET WILL
BE TO ADVISE THIS ADVISORY
COMMITTEE AS WELL AS DIRECTOR OF
NCI CONDUCT A TECHNICAL REVIEW
OF RAS RENEWAL PACKAGE. TO
ENSURE APPROPRIATENESS OF THE
PROPOSED RESEARCH TO OPTIMIZE
AND BALANCE PARTNERSHIPS BETWEEN
EXTRAMURAL RAS COMMUNITY AND
PROVIDE THEIR OVERALL
INDEPENDENT ASSESSMENT OF THE
RAS INITIATIVE RENEWAL AND
PROPOSED PLANS FOR FUTURE
RESEARCH AND THERAPEUTIC
DEVELOPMENT. SO WORK PRODUCT
WORKING GROUP IS WRITTEN
TECHNICAL REPORT AND
RECOMMENDATION TO BE PRESENTED
AT THE NEXT FNLAC MEETING
FEBRUARY OF 2023. UPON THIS
ADVISORY COMMITTEE ACCEPTANCE,
THIS REPORT RECOMMENDATION WILL
PROVIDE TO THE NCI DIRECTOR.
FINALLY I WOULD LIKE TO DESCRIBE
THE PROPOSED MAKE UP OF THIS NEW
WORKING GROUP. SO THE PROPOSED
COMPOSITION WOULD BE MADE OF
HIGHLY REGARDED SIGNISTS
RECRUITED FROM BOTH ACADEMIC
RESEARCH COMMUNITY AS WELL AS
PRIVATE SECTOR. SCIENTIFIC
EXCELLENCE AND DOMAIN EXPERTISE
IS DRAWN FROM A VARIETY OF
ACADEMIC RAS AND CANCER BIOLOGY
RESEARCHERS, STRUCTURAL
BIOLOGIST, AND BIOPHARMACEUTICAL
AND RESEARCH INSTITUTE EXPERTS
WITH PERTINENT RELEVANT DRUG
DISCOVERY DEVELOPMENT
EXPERIENCE. THIS WORKING GROUP
WILL BE DEMOGRAPHICALLY BALANCED
IN LINE WITH NCI BEST PRACTICES
AND CURRENT INITIATIVES. SO
THIS CONCLUDES MY BRIEF
PRESENTATION. HAPPY TO ADDRESS
QUESTIONS THE ADVISORY COMMITTEE
MAY HAVE. THANK YOU FOR YOUR
ATTENTION.
>>THANK YOU, DR. KANEE. WE HAVE
TIME FOR BRIEF QUESTIONS. THEN
DISCUSS AND THEN TAKE VOTE.
THERE IS ANOTHER ITEM ON AGENDA
THAT IS NOT LISTED THAT WE HAVE
TO APPROVE SO ANY QUESTIONS FOR
DR. KANE? PRETTY STRAIGHT
FORWARD INITIATIVE THAT WILL
COME BACK TO IN FEBRUARY. IF
NOT, CAN I HAVE A MOTION TO
APPROVE? FIRST FOR APPROVAL?
>>SECOND.
>>ALL THOSE IN FAVOR. ANY
OPPOSED OR ABSTAINED. THANK YOU
VERY MUCH.
>>THANK YOU.
>>THANK YOU, DR. KANEE. NOT ON
THE AYEN DA WAS A LATE ITEM AND
I THINK THE DOCUMENTS WERE SENT
TO EVERYBODY, THEY ARE UPDATED
VISION STATEMENTS FOR AD HOC
CRYOELECTRON MICROSCOPE
OVERSIGHT COMMITTEE AND
OVERSIGHT WORKING GROUP FROM
CRYOELECTRON MICROSCOPY PROGRAM
ANYONE HAVE ANY QUESTIONS?
EVERYONE RECEIVE THOSE? BECAUSE
I NEED MOTION TO APPROVE BOTH
THESE MISSION STATEMENTS UNLESS
THERE'S SOME FURTHER DISCUSSION
ON THEM. ALL GOOD? OKAY. MOTION
TO APPROVE. THANKS,LY VIRGINIA
SECOND, ALL THOSE IN FAVOR, ANY
FURTHER DISCUSSION? OKAY. SO
LODUC, ANY THING ELSE WE NEED TO
DO TODAY?
>>I DON'T HAVE ANYTHING TO ADD.
THANK YOU FOR YOUR SERVING.
I WANT TO THANK YOU VERY MUCH
FOR YOUR PARTICIPATION.
>>THANKS, EVERYBODY. THIS WAS A
GREAT GROUP, MONICA, WE WELCOME
YOU, IT IS GOING TO -- THIS IS A
FUN GROUP AND WE WILL HAVE MORE
FUN IN PERSON. LOOK FORWARD TO
THAT. IF I HAVE NO OTHER
COMMENTS OR CONCERNS, I WILL
ADJOURN THE MEETING. THANK YOU
SO MUCH.
>>THANK YOU SO MUCH EVERYONE.