>>WELCOME TO
THE WEBINAR ON VACCINES AND
GLOBAL HEALTH.
MY NAME IS -- OF ALLERGY AND
INFECTIOUS DISEASE ALSO KNOWN
AS NIAID.
ON BEHALF OF MY COLLEAGUES WHO
ARE PART OF THESE COMMITTEES,
WE WOULD LIKE TO WELCOME YOU
TO TODAY'S WEBINAR.
FIRST A LITTLE BIT OF
INFORMATION ABOUT GVIRF.
THE FVIRF AND ORGANIZATION
WEBINAR SERIES ARE ORGANIZED
BY NIAID AND THE BILL AND
MELINDA GATES FOUNDATION WITH
THE SPECIFIC GOAL OF
IMMUNIZATION AGENDA 2030.
TODAY'S TALK IS ABOUT A TANS
AND -- A TANS AND FORMULATION
TECHNOLOGY.
WE ALSO PROVIDE A SERIES OF
FLASH TALKS AT THE END TO
FACILITATE GLOBAL ACCESS TO
THIS TECHNOLOGY.
WE HAVE LINED UP A PANEL OF
EXPERTS FOR TODAY AND HOPE YOU
WILL ENJOY TODAY'S WEBINAR.
WITHOUT FURTHER ADIEU, LET'S
MOVE ON TO SECTION 1, GLOBAL
DEMANDS FOR VACCINE ADJUTANTS.
IT WILL BE CHAIRED BY Dr.
FINANCIAL OFFICER AND ME SO
CHRIS, TAKE IT AWAY.
>>HI, I AM VERY PLEASED TO
CO-CHAIR THIS SESSION WITH
ANNIE AND A SERIES OF
PANELISTS AND SPEAKERS I THINK
YOU WILL FIND VERY ENGAGING SO
LET'S MOVE ON TO NICHOLAS
COLLINS WHO FORMULATED THE
VACCINE INSTITUTE AND SERVES
AS ITS CEO.
NICHOLAS?
CHRISTOPHER FOX.
>>THANK YOU VERY MUCH.
CAN YOU SEE MY SCREEN?
>>YES.
>>IS IT PRESENTATION MODE?
SUCH A PLEASURE TO BE HERE AND
THANK YOU VERY MUCH CHRIS FOR
THIS KIND INTRODUCTION.
THANK YOU VERY MUCH TO THE
ORGANIZER AND TO BE PART OF A
PRODUCTION ON A VERY IMPORTANT
TOPIC.
I AM GOING TO SPEAK ON VACCINE
ADJUVANTS AND THE NEED FOR A
GLOBAL MARKET.
TO START OFF, I WOULD LIKE TO
SHARE A STORY ABOUT A FEW
PEOPLE WHO HAD A VISION,
COMMON VISION FROM 2012.
WHEN WE CREATED THE VACCINE
FORMULATION INSTITUTE THANKS
TO THE WORLD HEALTH
ORGANIZATION, WE HAD TWO
MISSIONS IN MIND, ONE TO BE
THE GATEKEEPER OF ADJUTANTS
AND PROVIDE THEM UNDER OPEN
ACCESS TO THE COMMUNITY AND TO
DISSEMINATE FORMULATION
KNOW-HOW TO VACCINE
RESEARCHERS AND DEVELOPERS.
TEN YEARS LATER, WE HAVE THIS
IN PLACE AND OF COURSE WOULD
NOT BE POSSIBLE WITHOUT THE
FOUNDERS AND ARE REALLY
GRATEFUL FOR THE CHEMISTS,
FORMULATION EXPERTS,
IMLODGISTS AND PROJECT
MANAGERS.
WE HAVE TWO LABORATORIES AND
NOW THE VACCINES ARE STRIPPED
AT LARGE SCALE WITH OPEN
ACCESS.
MY COLLEAGUE WILL COME BACK TO
THE ADJUTANT PORTFOLIO FOR
YOU.
THIS WILL BE PRESENTED IN TWO
PARTS.
I WOULD LIKE TO DO A VERY
QUICK ADJUTANT TALK ON THE
LANDSCAPE BEFORE AND AFTER
H1N1 ININFLUENZA AND COVID-19
AND THEN THE CURRENT NEEDS AND
HOW TO IMPROVE EQUITABLE
ACCESS AND AFFORD FORDABILITY
OF ADJUVANTED VACCINES AND HOW
TO FIND SOLUTIONS FOR OPEN
ACCESS PERSPECTIVES.
SO TO LOOK AT THE SOLUTION,
THERE ARE ONLY THREE ADJUVANTS
IN THE VACCINE.
ONLY THREE WERE AVAILABLE TO
THE VACCINE COMMUNITY WITHOUT
ANY LICENSING DEGREE REQUIRED.
THESE ARE ONLY ALUMINUM SALTS
UNDER OPEN-ACCESS TERMS,
AVAILABLE WITHOUT ANY
LICENSING AGREEMENT.
FOR THE PANDEMIC THERE WERE
SPEC NEEDS AND SEVERAL BILLION
DOSES OF ININFLUENZA VACCINES
AT AN AFFORDABLE PRICE IN A
SHORT TIME FRAME AND THERE
WERE CHALLENGES IN DEVELOPMENT
WITH THE VACCINE COMMUNITY TO
GAIN IMPROVED ACCESS, IMPROVED
FORMULATION AND EVALUATION OF
ADJUVANTED VACCINES.
TEN YEARS LATER, THEN WE CAN
SAY THAT IT HAS BEEN PROPERLY
TRANSFORMED AND REACHED AN
AMOUNT OF SUCCESS, AN
IMPORTANT ACHIEVEMENT.
THERE HAVE BEEN MANY, MANY NEW
ADJUVANTS THAT HAVE REACHED
THE STATE OF BEING INCLUDED IN
VACCINES.
THEY ARE BENEFITTING A LOT OF
DIFFERENT AGES, THEY ARE
IMPROVING THE RESPONSES AND
COVERING A MAGNITUDE OF IMMUNE
RESPONSES.
THIS IS REFLECTED WHEN WE SEE
THE ADJUTANT INCLUDED IN
VACCINES SINCE 2009 BUT STILL
THE CHALLENGE AS YOU CAN SEE
HERE, THERE ARE ONLY A FEW
ADJUVANTS AND WITH NO LICENSE
REQUIRED, ONLY TWO OF THEM
WITH THE LIMITATIONS FOR THE
VACCINE AND ON TOP OF THAT, MY
COLLEAGUES WILL TALK ABOUT
THIS IN MORE DETAIL, WE HAVE
LEARNED FROM COVID-19 PANDEMIC
THAT THERE WERE ISSUES WITH
ACCESS TO VACCINES AND
AFFORDABLE VACCINE ACCESS.
THAT BRINGS ME TO THE SECOND
PART OF MY PRESENTATION WHERE
PROPOSED RELIEF NEEDS TO BE
FOR THE -- AND HOW TO IMPROVE
EQUITABLE ACCESS AND
AFFORDABILITY.
THE FIRST PART, IF A TANS ARE
NOT AVAILABLE AT GM P, LIMITED
INTEREST FROM VACCINE
DEVELOPERS.
WE ALSO WANT TO ELICIT AN
ADJUTANT OPTION BECAUSE EVERY
SINGLE ADJUTANT HAS THEIR OWN
PROPERTIES.
THEY HAVE THEIR OWN STUDIES
AND PROVIDE CRITICAL
INFORMATION ON THE CLASS OR
TYPE OF ADJUVANT REQUIRED FOR
A GIVEN ANTIGEN OR INDICATION.
IT NEEDS TO BE IDEALLY
PERFORMED BY A NEUTRAL
LABORATORY EARLY ON FOR A
SPECIFIC ADJUTANT CLASS OR
SPECIFIC ADJUTANT TYPE IS
REQUIRED FOR ONE VACCINE.
ANOTHER NEED, CORRELATION FROM
THE FIRST ONE IS TO LIBERATE
MORE IN ADJUTANT COOPERATION
AND SAFETY.
YOU GET TO SEE HERE A RATHER
COMPLEX SOLUTION ON EQUAL BASE
WITH TWO COMPOSITIONS.
ONE NEEDS TO FIND THE BEST
COMPOSITION, THEN MANUFACTURE
THE CONCENTRATIONS.
THEN MORE ACTIVITY IS REQUIRED
WHEN WE START MANUFACTURING
AND FINALLY WE LOOK AT THE
LIMITATION ON THE BEST
MODERATE DEL BUT THIS IS NOT
WHERE IT STARTS BECAUSE IN THE
LIPID IMMUNOPROCESS, WE NEED
TO MONITOR AND KEEP GOING WITH
THE PROCESS.
ANOTHER NEED IS NOT TO JUST
GET MORE ADJUTANT BUT DEVELOP
NEW A TANS AND THIS PROCESS IS
VERY SURE WHERE THEY CAN MAKE
A DIFFERENCE AND WHERE THEY
ARE NOT.
THIS FROM A PAPER FROM LYKINS
AND FOX ON THE NEED TO DEVELOP
NEW A TANS FOR THE NEXT HE
NEXT GENERATION OF VACCINE.
WE HAVE FOR EACH COUNTRY OF
COMPONENT PRODUCTION AND FINAL
VACCINE ADMINISTRATION BUT WE
NEED TO BE AWARE THERE IS A
PARTICULAR BROADER SCOPE
NEEDED AND WE NEED TO BE AWARE
OF THE TIMELINE VERSUS THE
REMAINING TIME OF PATENT LIFE.
WE NEED TO KEEP IN MIND THIS
IS ALL A MOVING TARGET AND
REGULAR UPDATES ARE REQUIRED
WHICH ARE COSTLY AND
TIME-CONSUMING.
ONCE WE HAVE THE DECISION
MADE, THEN WE NEED TO MOVE
FORWARD WITH ITERATION.
KEEPING IN MIND THE EXEMPTIONS
TO PATENT PROTECTION AND LEGAL
PROVISIONS TO PROGRESS DURING
THE FINAL-YEAR-OLD -- YEARS OF
A PATENT TERM TO BE READY FOR
RAPID MARKET ENTRY, KNOWLEDGE
OF NATIONAL PATENT LAWS AND
ALSO TO KEEP IN MIND THAT
SOMETIMES THERE IS NEGOTIATION
WITH A PATENT OWNER WHICH IS
OFTEN LENGTHY AND COMPLICATED
AND THE VACCINE CAN BE BLOCKED
BECAUSE OF SOME OLDER IP
GENERATED FOR A DIFFERENT
TIMELINE.
AND FINALLY WE NEED TO LOOK AT
THE BUSINESS MODEL.
WE ARE AWARE OF THE MOST
CLASSIC MODEL FOR ADJUTANT
FORMATION, A CLASSICAL OUTLIES
LICENSING-- OUTLICENSING MODEL
BETWEEN THE OWNER AND THE
DEVELOPER AS YOU SEE HERE.
IN MANY CASES, THE OWNER IS
ALSO THE VACCINE DEVELOPER
WHICH COMPLICATED THE
SITUATION BECAUSE LOGICALLY
THERE WILL BE LESS FOR THE
OWNER FOR CERTAIN TYPE OF
INDICATION.
IF THERE IS A NEW OWNER FOR
OUTLICENSING AGREEMENT, THEN A
NEW MODEL NEEDS TO BE PUT IN
PLACE.
AND IN A NUTSHELL, THE ACCESS
MODEL WHICH WE WORKED FROM OUR
OWN EXPERIENCE COULD PROVIDE
DIFFERENT POSSIBILITIES.
HERE YOU HAVE A DEAL BETWEEN
AN ADJUTANT OWNER AND ADJUTANT
PRODUCER WHICH IS A
SPECIALIZED COMPANY WHERE
THERE IS ONE DEAL BETWEEN THE
TWO COMPANIES AND IN THERE, WE
HAVE A SITUATION WHERE THE
PRODUCTION IS APPLIED FOR BOTH
FOR AN OPEN ACCESS MODEL.
THIS IS THE MODEL IN WHICH WE
ARE USING FROM 2020.
IN CONCLUSION, THERE IS A NEED
FOR MORE ADJUTANTS, THERE IS A
NEED FOR MORE PREPARATION FOR
TESTING.
WE NEED TO BETTER UNDERSTAND
THE FTO AND TO IMPLEMENT
BUSINESS MODELS COMPATIBLE
WITH GLOBAL HEALTH CHALLENGES.
THANK YOU FOR YOUR ATTENTION.
>>THANK YOU SO MUCH,
NICHOLAS.
OUR NEXT SPEAKER WILL BE DAN
FULLEN WHO IS THE SENIOR
MANAGER AT SEPI AND WE WILL BE
GIVEN A TWO-MINUTE WARNING
WHEN YOU NEED TO BRING YOUR
TALK TO AN END.
>>CAN I SHARE MY SCREEN?
>>YES, PLEASE.
>>CAN YOU PUT IT IN
PRESENTATION MODE, PLEASE?
>>YES, THANK YOU.
SO MY NAME IS DANIEL FULLEN, I
AM A SENIOR SCIENTIST MANAGER
OFFICE OF TECHNOLOGY AT CEPI.
NOW THAT WE ARE POST PANDEMIC
OVER A YEAR, YOU CAN SEE FROM
THE LINE AND DEVELOPMENT --
[INDISCERNIBLE]
SO TODAY WE WILL GO THROUGH
THE VACCINE AND THE LABELING
AND SO TODAY WE WILL GO
THROUGH WHAT MAKES AN OPTIMAL
ADJUVANT, REQUIREMENTS FOR THE
PANDEMIC PREPAREDNESS AND HOW
WE ENSURE THAT ADJUVANTS ARE
WHERE THEY ARE WHEN WE NEED
THEM.
SO WHAT WE HAVE TODAY FOR THE
OPTIMAL ADJUVANT, AND THE
ANSWER IS IT DEPENDS ON ON THE
COMPOUND SPECIFICS.
IS IT FOR THE ENTIRE
POPULATION, PEDIATRIC AND THE
PLATFORM, MRNA, DNA, ET
CETERA.
AND WHAT TYPE OF IMMUNE
RESPONSE ARE WE LOOKING FOR,
QUALITY OF RESPONSE, EFFICACY,
BREADTH, DURATION AND ALSO
NEED TO LOOK AT THE PATHOGEN
AS WELL.
THE SIGNALING AS WELL MUST BE
TAKEN INTO CONSIDERATION AND
ROUTE OF ADMINISTRATION AS
WELL.
THIS IS JUST ONE EXAMPLE OF
WHAT ADJUTANT WAS USED IN WHAT
SITUATION.
RUNNING A HEAD TO HEAD
COMPARISON TO DATE, THE
ADJUVANTS THAT APPEAR MORE
EFFECTIVE FOR ACUTE INFECTIONS
AS YOU CAN SEE HERE.
[INDISCERNIBLE]
WE HAVE LIPOSOMAL ADJUVANTS
THAT APPEAR MOST EFFECTIVE FOR
CHRONIC INFECTIONS FOR HBV SO
WHAT ARE THE KEY ADJUTANTS FOR
DISTRIBUTION?
WE HAVE ONE HERE THE
REQUIREMENTS OF ADJUVANT FOR
PANDEMIC PREPAREDNESS AND LOOK
AT THE IMMUNE RESPONSE,
LOOKING AT A WIDE POPULATION,
ELDERLY AND FOR CHILDREN AS
WELL AND IT NEEDS TO BE
ADAPTABLE AS WELL.
THE SOURCE OF ADJUTANT NEEDS
TO BE HAVE AS FEW COMPONENTS
AS POSSIBLE AND TESTED
CLINICALLY, VERY IMPORTANT FOR
IT TO BE STABLE --
[INDISCERNIBLE]
AS MENTIONED AS WELL, IT HAS
TO BE REALLY AVAILABLE AND NOT
LIMITED BY IP RESTRICTIONS.
IT MUST BE ABLE TO BE PRODUCED
AT SCALE AND IN DIFFERENT
TERRITORIES.
THERE IS A NEED TO REGULATE
IT --
[INDISCERNIBLE]
THE PANDEMIC STRAIN IS
IMPORTANT BUT THERE COULD BE
DOSE SPARING POTENTIAL.
FORTUNATELY WE HAVE SEEN THAT
IT MAY NOT BE THE PERFECT
ADJUTANT BUT IT CAN BE DONE.
I THINK IT VERY IMPORTANT TO
HAVE ADJUTANTS AVAILABLE AT
LEAST FOR THE FIRST RESPONSE
WHEREAS PREVIOUSLY AS THE NEXT
SLIDE SHOWS, WE HAVE
ESTABLISHED SAFETY PROFILE AND
STABLE.
IT MUST BE CLINICALLY TESTED
FOR A BROAD IMMUNE RESPONSE
AND COMPATIBILITY.
THE ADJUTANT AVAILABLE NEEDS
TO BE AVAILABLE WHERE WE NEED
THEM AND SOMETIMES USING
TECHNOLOGY TO GET THEM TO THE
RIGHT PLACE.
[INDISCERNIBLE]
AND THE SCALE AS WELL, IT IS
REALLY IMPORTANT TO GET THE
VACCINES OUT THERE.
SO THERE ARE TWO TYPES THEN.
THE SQUALENE PACED ADJUVANTS
AND ALUM ADJUVANTS.
IN AN OUTBREAK SCENARIO, THESE
CAN BE PRODUCED FOR THE
VACCINE AND ROLLED OUT IN A
PROGRAM.
THERE IS ALSO THE QUESTION OF
STOCKPILE, WHERE WE WILL
STOCKPILE, PHYSICAL LOCATION
AND ALSO THE STRENGTH OF THE.
[INDISCERNIBLE]
GIVEN THERE IS A PLACE TO
STOCKPILE, WE NEED TO LOOK AT
LONGER PERIODS FOR STOCKPILE.
THERE IS ALSO ADJUTANT
FORMULATION.
[INDISCERNIBLE]
SO A SMALLER PRODUCTION WOULD
MINIMIZE THE VACCINE.
IT IS ALSO IMPORTANT IN IT IS
DEVELOPED IN A COUNTRY WITH A
WARM BASE SO YOU HAVE YOUR
VACCINE MANUFACTURING MAKING,
MALARIA, HIV, ET CETERA, AND
THE PRODUCTION CAN BE SWITCHED
FOR THE ADJUTANT.
AND TO ENABLE IT AS WELL, WE
LOOK AT THE ADJUTANT PLATFORM.
THE IDEAL WOULD BE IF WE HAVE
LOW ADJUTANT SUPPLY, WE HAVE
THE POTENTIAL FOR DOSE
SPARING.
SO THE VACCINE IS GROWING
ESSENTIALLY IN A VERY LOW
REGION --
[INDISCERNIBLE]
LIMITING THE BORDERS WHEN
BORDERS CLOSE AND ALSO --
[INDISCERNIBLE]
ANALYSIS.
SO.
>>TIME'S UP.
>>SO IN SUMMARY, WE HAVE THE
ADJUVANTS FOR EXACTLY WHAT WE
NEED, HOWEVER THE BIG ISSUE IS
THE SUPPLY WHERE YOU NEED THEM
AND THE INTRODUCTION TO BE
MORE GLOBAL.
WE NEED MORE INDEPENDENCE BY
EACH COUNTRY AND EXPORT --
[INDISCERNIBLE]
THANK YOU.
>>THANK YOU DANIEL FOR THAT
PERSPECTIVE.
OUR THIRD SPEAKER WILL BE THE
CEO OF MADVAC.
MICHELLE?
>>HELLO EVERYONE, I WOULD
LIKE TO THANK THE ORGANIZER
AND CHAIR FOR THIS OPPORTUNITY
TO TELL ABOUT OUR ADJUVANTS
FOR GLOBAL HEALTH.
MY TALK IS IN TWO SECTIONS.
FIRST, LET ME TELL YOU ABOUT
THE VACCINES.
I STARTED IN 2016 AFTER WHAT
WE GET FROM THE U.S. FOR THE
VACCINE AND GLOBAL HEALTH
PROJECT.
SO THE COMPANIES NOW FROM
CHINA AND AND THE U.S.
ALL OF THE VACCINES USING THE
COMPONENTS FROM MAXVAX VACCINE
PIPELINE.
SINGLES WE HAVE IN THE U.S.
AND CHINA AS WELL.
ALL THE ADJUTANT USING THIS
VACCINE FORMULATION IS MADE
IN-HOUSE BY MAX MAXVAX.
THIS IS PART OF THE PLATFORM
WE ARE WORKING ON.
FIRST OF ALL, WOULD I WE ARE
WORKING ON ADJUTANTS, THE
PROGRAM ACCESSIBILITY HAS
SHOWN THAT ADJUVANTS ARE NOT
ONE SIZE FITS ALL FOR
DIFFERENT TYPES OF VACCINES.
MAXVAX HAS A LIBRARY OF
ADJUTANT MOLECULES AND
FORMULATION THAT CAN BE
TAILORED BY DIFFERENT
VACCINES.
THERE IS QUALITY AND SCALE,
AFFORDABILITY AND
SUSTAINABILITY AND SUPPLY
SECURITY.
THESE ARE THE ISSUES FOR
GLOBAL VACCINE AND WE SEE
OTHER ISSUES WHEN WE FIRST
DEVELOPED OUR COMPANY SO WE AT
MAXVAX LOOK AT THE
AVAILABILITY WITH THE GOAL TO
BECOME SELF-SUFFICIENT FOR
PARTNERS INTERESTED IN
ADJUVANTS AND FORMULATIONS.
OUR FOCUS IS ON IMPROVING THE
QUALITY, ACCESS AND
AFFORDABILITY OF ADVANCED
ADJUVANTS.
IN HOUSE, WE LOOK AT EXPERTISE
IN CHEMICAL SYNTHESIS OF
ADJUVANTS AND NUCLEIC ACIDS,
R&D AND INDUSTRIAL PLANTS
AVAILABLE TO PRO PRODUCE
ADJUVANTS AND FORMULATIONS.
SO WHAT WE HAVE TODAY,
PRODUCED AT MAXVAX WE HAVE 20
RESEARCH-GRADE ADJUVANT
MOLECULES COVERING COMMON
CLASSES AND HIGH DEGREE OF IND
READY GM P GRADE MATERIALS.
WE HAVE FOUR ADJUVANT
MOLECULES WITH THREE DELIVERY
SYSTEMS AND FOUR COMBINATION
ADJUVANTS.
SO WE SEE WHAT WE HAVE FOR
ADJUVANT CLASSES, WE HAVE
QS-21, P.M. OLY, MPL, CPG AND
LIPIDS FOR LIPOSOMES AND
AGOIFTS AND INKT CLASS.
SO LET ME EXPLAIN WHAT THEY
ARE.
WE HAVE MATERIAL PURIFIED FROM
PLANT EXTRACT USED IN VACCINE
IN PHASE II STUDY.
THIS BATCH SIZE IS EQUIVALENT
TO 1 MILLION DOSES.
WE PLAN FOR SMALL SCALE
PRODUCTION NEXT YEAR.
BUT THIS MATERIAL IS LOOKING
AT PO LY OR I: C.
THE MOLECULES ARE NOT
OPTIMIZED FOR MAX PRODUCTION
SO WE HAVE O OPTIMIZE THE I:
C.
THIS IS OPTIMIZED FOR TWO
MILLION DOSES.
WE HAVE FOUR SYNTHETIC MPL
MOLECULES.
THE GM P MP L.A. IS MADE AT
AROUND 200 BATCH SIZE AND
EQUIVALENT TO FOUR MILLION
DOSES.
THE SCALE IS MUCH HIGHER THAN
THE PURIFIED AND ALSO CAN BE
UTILIZED TO SCALE AND
TRANSFERRED.
THE NEXT MOLECULE IS FOR WPG
AND WE DO HAVE A PLAN TO MAKE
THIS COMMERCIAL SCALE NEXT
YEAR.
MOST MATERIAL MOLECULE
REQUIRED TO MAKE ADJUVANT, WE
USE ALUMINUM HYDROXIDE, OIL IN
WATER, LIPOSOMES AND THIS CAN
BE MADE IN COMMERCIAL SCALE.
THE ADJUVANT FOR 2.5 MILLION
DOSES OF VACCINE.
WE HAVE THE RIGHT COMBINATION,
WE CALL THAT COMBINATION
ADJUVANT FOR OUR OWN VACCINES
TO USE.
THIS OUR OWN FORMULATION AND
GET WIDE IMMUNE RESPONSE.
THE OIL IN WATER EMULSION WITH
ONE ADJUVANT PROMOTE
ANTIBODIES AND DEVELOP
PRECLINICAL.
WE HAVE USED THIS ADJUVANT IN
COVID VACCINE IN CHINA.
WE ARE ALSO USING THIS
ADJUVANT FOR SEVERAL OTHER
VACCINES IN DEVELOPMENT LATER
THIS YEAR AND THE NEXT YEAR.
SO THE ADJUVANT MA 105, IT IS
LIPOSOME AND TWO ADJUVANTS FOR
ANTIBODIES RESPONSE, CD4,
T-CELLS RESPONSE AND WE HAVE
COUPLE OF VACCINES WE PLAN TO
DEVELOP FOR PHASE II.
WE ALSO HAVE ANOTHER
FORMULATION CALLED AYK103, A
LIPOSOME WITH TWO ADJUVANT
MOLECULES.
IT SHOW M1, CD4, CD8 AND T
CELLS RESPONSE.
CURRENTLY WE INVESTIGATE
TREATMENT FOR SOLID TUMORS.
SO ALL THESE FORMULATIONS ARE
MADE UNDER GM P AT COMMERCIAL
SCALE AND WORK WITH
FORMULATION CODES.
WE ALSO LOOK AT THE FACILITY
FOR VACCINE AND ON TOP LEFT WE
HAVE VACCINE R&D CENTER FOR
FORMULATIONS AND VACCINES FROM
PHASE 1 AND II STUDIES
DECEMBER.
ON ON THE TOP RIGHT, WE HAVE
ADJUVANT R&D CENTER IN
SHANGHAI AND CURRENTLY WE MAKE
VACCINES TO SCALE FOR
ANTIDOTE.
ON BOTTOM LEFT WE HAVE VACCINE
MANUFACTURING PLANT WHERE WE
MAKE ADJUVANT FORMULATIONS AND
VACCINES AT COMMERCIAL SCALE.
WE HOPE THIS WILL BE OF
INTEREST TO POTENTIAL
PARTNERS.
SO WE CURRENTLY HAVE RESEARCH
WITH MOLECULES AND ALSO WE
HAVE ADJUVANT PLATFORM
AVAILABLE FOR FORMULATION.
THANK YOU.
>>THANK YOU.
SO WE APPRECIATE OUR THREE
SPEAKERS FOR THEIR UNIQUE
PERSPECTIVE AND WILL NOW MOVE
TO THE PANEL DISCUSSION.
AND IN ADDITION TO THE THREE
SPEAKERS YOU JUST HEARD FROM,
WE HAVE TWO SPEAKERS.
AND THE WAY THAT WE WILL DO
THE PANEL DISCUSSION IS WE
HAVE SELECTED A HANDFUL OF
QUESTIONS FROM THE MANY, MANY
QUESTIONS THAT WERE SUBMITTED
PRIOR TO THE WEBINAR AND
OBVIOUSLY WE WON'T HAVE TIME
TO GET TO ALL OF THEM.
ALSO WE SEE THERE ARE MANY
QUESTIONS IN Q&A SECTION HERE
OF THE WEBINAR AND THE PANEL
SPEAKERS WILL ATTEMPT TO GET
TO AS MANY OF THOSE AS THEY
CAN IN THAT Q&A PORTAL.
SO FOR NOW WE WOULD LIKE TO GO
TO KRISHNA AND PALO AND GIVE
THEM A FEW MINUTES TO
INTRODUCE THEMSELVES AND
ADDRESS ONE OF THE QUESTIONS
WE HAVE SELECTED.
SO KRISHNA, THE QUESTION FOR
YOU IS WHAT ARE THE MAIN
OBSTACLES AND POTENTIAL
SOLUTIONS FOR KNOWLEDGE
SHARING ON ADJUVANTS AND WE
WILL HAND IT OVER TO YOU TO
SHARE A COUPLE OF SLIDES AND
ADDRESS THAT QUESTION.
>>YEAH, THANKS, CHRIS.
I AM ENGAGED IN SACKS --
VACCINE AND ADJUTANTS AND IF
WE GO TO THE NEXT SLIDE, ONE
OF THE KEY ISSUES ONE HAS IS
KNOWLEDGE SHARING OF
INFORMATION ON PARTICULARLY
NEW ADJUTANTS AND THERE IS
QUITE AND YOU AN INCOMPLETE
KNOWLEDGE TRANSFER.
THE SECOND MAJOR PROBLEM IS
THE COMPLEXITY IN ATAPBT
CHARACTERIZATION -- ADJUTANT
CHARACTERIZATION, ESPECIALLY
IF YOU ARE IN A EMERGENCY
SITUATION, THIS NEEDS TO BE
DONE IN SHORT TIME AND SOME OF
THE POINTS MADE ON GM P AND
THE PREVIOUS SPEAKER, IT IS
MUCH MORE DEMANDING AND TO
TALK ABOUT NEW ADJUTANTS, YOU
NEED EXTENSIVE
CHARACTERIZATION.
THIS IS TO ENSURE SAFETY AND
MAKES IT DELAY IN VACCINE
DEVELOPMENT AND NEEDS
EXTENSIVE CHARACTERIZATION
THAT MAY NOT BE AVAILABLE IN
R&D STAGE DEVELOPMENT AND THIS
IS WHERE THE PROBLEM LIES.
THE MOMENT YOU START GETTING
INTO COMMERCIALIZATION AND
START WANTING TO DO HUMAN
TRIALS, THEN IT BECOMES A
HERCULEAN TASK TO DO.
SO THIS IS SOMETHING I THINK
HAS NOT GOT TEN MUCH ATTENTION
TILL NOW.
WE NEED TO UNDERSTAND THE
MECHANISM OF ACTION OF
ADJUTANTS BUT THAT IS NOT SO
MUCH AN OBSTACLE BECAUSE THERE
IS BASIC FUNDAMENTAL RESEARCH
GOING ON IN DIFFERENT LABS
ACROSS THE WORLD.
SO THESE ARE THE KEY TO ME,
EXPENSIVE, SAFETY
CHARACTERIZATION, MONITOR
CHARACTERIZATION WITH ADJUVANT
ALONE IN COMBINATION WITH THE
VACCINE FOLLOWED BY THE GM P
MANUFACTURER AND THEN LOOKING
AT IN TERMS OF COMPATIBILITY
WITH THE ADJUVANT.
BECAUSE THE ADJUVANT MAY BE
GOOD ENOUGH IN SHORT TERM
COMBINATION BUT IN LONG-TERM
STUDY, YOU NEED TO MAKE SURE
YOU HAVE GOOD ADJUVANT IN
HAND.
SO WHAT KIND OF SOLUTION WE
HAVE, THE NEXT SLIDE BRIEFLY
MENTIONS THOSE.
CERTAINLY WE NEED TO HAVE GOOD
COLLABORATION.
AGAIN A COUPLE OF EARLIER
SPEAKERS DID MENTION
COLLABORATION.
THERE HAS TO BE VERY CLEAR
OBJECTIVE OF USAGE BETWEEN
PARTNERS AND TRYING TO GET A
WIN-WIN APPROACH BY PARTIES.
IT IS NOT ABOUT LICENSING AND
ALL THOSE, IT IS MUCH MORE
THAN THAT.
AND CERTAINLY WORKING ON THE
YOU NEW ADJUVANTS,
SPECIFICALLY THOSE THAT ARE
SAFE AND EFFECTIVE AND IN
MARKET WHETHER THEY NEED
SLIGHT MODIFICATIONS OR EXTEND
THEM HAVE VACCINES WOULD BE
EASIER THAN YET ANOTHER NEW
ADJUVANT SO THESE ARE A COUPLE
OF THINGS TO BE MINDFUL OF.
THANK YOU, CHRIS.
>>THANK YOU, KRISHNA,
APPRECIATE THAT.
>>PALO, YOUR QUESTION IS IT
BETTER TO LOOK AT NEW ADJUVANT
SYSTEMS OR MODIFY THE CURRENT
AVAILABLE ONES TO INCREASE
PRODUCTIVITY AND AVAILABILITY?
>>HELLO EVERYBODY, THANKS FOR
THIS OPPORTUNITY TO BE HERE
AND ALL THE ORGANIZERS TOO.
I AM TRYING TO SHARE MY
SCREEN.
CAN YOU SHARE MY SCREEN?
>>NOT YET.
I CAN SHARE IT FOR YOU IF YOU
LIKE.
>>PLEASE, IF YOU CAN -- CAN
YOU GUYS SEE?
>>YES, CAN YOU PLACE IT IN
PRESENTATION MODE?
>>OKAY, SORRY, JUST A MINUTE.
OKAY, SO JUST TO TELL YOU A
LITTLE BIT, I WORK IN ADJUTANT
SCIENCE FOR MORE THAN 30 YEARS
AND THIS YEAR WE COMPLETE 122
YEARS OF FOUNDATION.
WE ARE THE MAIN MAKERS OF
VACCINES. AND THIS YEAR WE
PRODUCED AROUND 80 MILLION FLU
VACCINES SUPPLIED TO OUR
MINISTRY OF HEALTH AS WELL AS
PAHO AND UNICEF.
WE HAD THE GLOBAL THREAT AND
END UP WITH A TRIAL OF H7N9
USING A DISTRIBUTION OF WHAT
WE CALL ID160 WHICH IS A OIL
IN WATER SOLUTION.
SO THE QUESTION IS, IS IT
BETTER TO LOOK AT THE ADJUTANT
SYSTEMS OR MODIFY CURRENTLY
AVAILABLE ONES TO INCREASE
PRODUCTIVITY AND AVAILABILITY?
THIS DEPENDS CASE BY CASE.
YOU NEED A PRODUCER OF
WELL-ESTABLISHED ADJUVANT WITH
VOLUME CAPABILITY FOR MARKET.
BUT THE DECISION SHOULD BE
USED CASE BY CASE.
IF YOU ARE A PRODUCER WITH
VOLUME CAPABILITY FOR THE
MARKET, THEN YOU CAN START
LOOKING FOR NEW ADJUVANTS.
IF YOU ARE A PRODUCER OF A
WELL-ESTABLISHED ANTIGEN
HOWEVER YOU HAVE NO VOLUME
CAPABILITY FOR THE MARKET
DEMAND, I GUESS THAT YOU
SHOULD INCREASE YOUR
CAPABILITY AND YOU ALSO HAVE
SOME SPACE FOR RESOURCES --
FOR RESEARCH ON NEW ADJUTANTS.
IF YOU ARE A RESEARCHER
LOOKING FOR ANTIGEN FOR
VACCINE DEVELOPMENT, THEN
PROBABLY YOU HAVE THE ANTIGEN
ASSOCIATED WITH THE CORRELATES
OF PROTECTION.
SO THE EASIEST WAY IS TO TEST
FOR THE READY AND AVAILABLE
ADJUTANT.
IF THEY DON'T WORK AND YOUR
ADJUTANT IS REALLY OUT OF SYNC
WITH THE PROTECTION, THEN
PROBABLY YOU WILL NEED TO LOOK
FOR A COMBINATION OF ADJUVANT
OR LOOK FOR NEW ADJUVANT.
BUT IF YOUR ANTIGEN IS NOT SO
STRONGLY ASSOCIATED WITH
PROTECTION, PROBABLY YOU WILL
NEED TO CHANGE THE ANTIGEN.
SO I GUESS THAT IT WILL DEPEND
ON THE PERSPECTIVE OF THE
STAKEHOLDER AND OF COURSE WE
WILL NEED TO EXPAND OUR
PRODUCTION CAPABILITY OF T
GRADE ADJUTANTS WHICH IS BELOW
WHAT WE NEED GLOBALLY.
BUT ALSO THERE IS A LOT OF
SPACE FOR NEW ADJUTANTS AS
TALKED BY PREVIOUS SPEAKER.
THAT IS ALL, I GUESS, CHRIS.
>>THANK YOU, PALO.
OKAY, SO WE WILL NOW ADDRESS
SOME QUESTIONS TO OUR PREVIOUS
SPEAKERS AS WELL AND INVITE
OTHER PANELISTS TO CHIME IN
AND WHEN THEY WOULD LIKE TO.
SO DECKSLANG, A QUESTION TO
YOU.
WHAT ARE THE OPTIONS TO
ESTABLISH THE SAFETY OF
ADJUTANTS?
>>THAT IS A VERY GOOD
QUESTION.
CAN YOU HEAR ME?
>>YES.
>>I AM NOT SURE I HAVE A
ANSWER TO THAT.
YOU HAVE TO UNDERSTAND THE
NEEDS SO WE CAN MAKE
MODIFICATION.
SO I THINK WE HAVE TWO
OPTIONS.
ONE IS TO DO IT YOURSELF.
TWO, PREPARE THAT.
YOU KNOW, WE CREATE POPULAR
ETHICS.
WE START TO DO IT OURSELVES,
MAKE THE FORMULATION AND ALSO
THE ADJUVANT VACCINE SO WE USE
THOSE INFORMATION.
THEN WE LOOK AT THE
INFORMATION OF PIPELINE,
WHETHER IT IS AVAILABLE AND
USE THAT INFORMATION TO
SUPPORT THAT.
AND THEN WE USE THE VACCINE
FROM CHINA AND U.S.
SO THIS IS NOT BROADLY
AVAILABLE TO OTHERS HOWEVER WE
WOULD WELCOME WITH THE OTHER
VACCINE DEVELOPERS TO VIEW
THIS AND MAKE BROADER
AVAILABLE AND WOULD LOOK AT
INTERNATIONAL AGENCY FOR THIS
PROCESS SO THERE IS MORE
LEGITIMATE AND ALSO BE MORE
ACCESSIBLE TO OTHERS.
SO I AM NOT SURE THIS IS A
GOOD ANSWER BUT HOPEFULLY
OTHER SPEAKERS HAVE BETTER
VIEWS ON THIS.
THANK YOU.
>>THANK YOU, DECKSIANG.
ANY-- -- DEXIANG.
ANY OTHER SPEAKERS LIKE TO
WEIGH IN ON THIS?
>>YES, IF YOUR APPROACH IS
NOT AVAILABLE, YOU NEED TO
CONSIDER MAKING IT AVAILABLE
TO -- DISCERN.
[INDISCERNIBLE]
>>THIS IS SOMETHING THAT WE
SAID IN THE BEGINNING, THAT WE
NEED TO REALLY WORK ON IT.
OTHERWISE NO ADJUTANT CAN BE
COMMERCIALLY SUCCESSFUL.
WE HAVE SIMILAR PROBLEM THAT
THE PREVIOUS SPEAKER
MENTIONED.
WE HAD TO GO FOR EVERYTHING
OUTSIDE SO THAT IS THE ONLY
ANSWER IT LOOKS LIKE AND YOU
HAVE TO DO IT FOR EVERY
VACCINE IN COMBINATION WHICH
IS QUITE A LOT OF MATERIAL.
UNLESS THE ORGANIZATIONS HAVE
THE NORMAL ADJUTANT ACCELERANT
AND WILLING TO PARTNER, THEN
YOU COULD USE THEM, OTHERWISE
THE NORMAL ADJUTANT WOULD NOT
BE ENOUGH.
>>OKAY, THANK YOU.
DANIEL, YOU MIGHT WANT TO TAKE
THE FIRST STAB AT THIS ONE.
WHICH NORMAL VACCINE
CANDIDATES WILL BENEFIT FROM
GREATER ADJUVANTS IN YOUR
OPINION?
>>WELL, I THINK WHATEVER IS
COMPATIBLE TO RESEARCH.
MOST VACCINES BENEFIT FROM
BROADER ACCESS OF ADJUTANTS.
IF YOU CAN SELECT YOUR
ADJUTANTS EARLY ON AND ARE
ABLE TO MAKE THE VACCINE
ADJUTANT EARLY ON, YOU --
[INDISCERNIBLE]
WHEREAS IN THE PAST ALTHOUGH
THE VACCINE DEVELOPERS MAKE
THEIR OWN ADJUTANTS, IF THEY
CAN'T AFFORD TO DO THAT, IT IS
VERY MUCH USING THE ADJUTANT
THEY CAN GET THEIR HANDS ON
AND MAKE A SOON FOR -- VACCINE
FOR THAT.
WE ARE WORKING ON A PROGRAM TO
DO THAT -- [ INDISCERNIBLE ]
AND THE IDEA HERE IS THE
ADJUTANT BE AVAILABLE IN A
PRE-TERM MODEL SO TO GET THE
ADJUTANTS EARLY ON FOR THE
VACCINE.
>>ANY OTHER PANELISTS WANT TO
SPEAK TO THAT?
>>CANNOT AGREE WITH YOU MORE
ON THE IMPORTANCE OF THESE
COMPARATIVE STUDIES.
IF THE VACCINE MAKER KNOWS A
SPECIFIC TYPE OF ADJUTANT OR
LIPOSOME OR SPECIFIC
CONTAINING ADJUVANT IS IT NOT
MATCH WELL IN THE VACCINE TO
BE USED, IT IS NOT SAVING
TIME.
AND FAIRLY EARLY ON IF YOU ARE
PROMOTING THEM, THIS IS GIVING
YOU AN INDICATION OF WHERE YOU
CAN GO RATHER THAN MAKING
CHOICES BY DEFAULT.
DURING THE PANDEMIC MANY
VACCINE MAKERS GOT THEIR HANDS
ON THE ADJUTANT BY DEFAULT.
SO IF YOU KNOW AHEAD OF TIME
YOU CAN GO TO A ADJUTANT MAKER
OR DIFFERENT MANUFACTURES WHO
HAVE ALREADY THE ADJUTANT THAT
IS READY BUT ESSENTIALLY IT IS
KNOWING WHICH ADJUTANT WORKS
FOR MY VACCINE IS CRUCIAL.
>>THANK YOU, NICHOLAS.
I AM SORRY, THERE WAS ANOTHER
RESPONSE ON THAT?
>>LOOKING AT THE VACCINE
ADJUTANT, IF WE CAN HAVE THE
RESULTS COMPARATIVE WITH THE
WELL-ESTABLISHED ADJUVANT, SO
THEN WE CAN UNDERSTAND MUCH
MORE IF THE ADJUTANTS ARE
WORKING.
>>THANK YOU, PALO.
SO I THINK THIS IS A GOOD
QUESTION TO END ON AND
NICHOLAS, I WILL ASK YOU TO
START OFF THE RESPONSE ON
THIS.
THE QUESTION IS HOW CAN
EQUITABLE ACCESS AND
AFFORDABILITY OF ADJUVANT
TECHNOLOGY BE ENABLED
WORLDWIDE?
>>GOOD QUESTION, CHRIS.
I THINK WE WOULD NOT BE HERE
IF WE COULD ANSWER THE
QUESTION ALREADY.
MAYBE COMPLIMENTING ON WHAT I
SAID BEFORE DURING THE TALKS,
I THINK WE HAVE AT LEAST TWO
THINGS TO CONSIDER, ONE IS ON
THE TECHNICAL SOLUTION AND
INNOVATION AND THE SECOND ONE
IS MORE OF A BUSINESS MODEL.
FOR INNOVATION, WE KNOW THERE
ARE MANY FOLKS RIGHT NOW DOING
SUCH THINGS BUT WE NEED TO
INCREASE AND IMPROVE THEM SO
THE FOLKS WORKING ON THESE, WE
NEED TO INNOVATE ON THE
PROCESSES BECAUSE THE CHEAPER
ADJUVANT WILL BE THE ONE YOU
GET THE MOST VACCINES.
THERE IS ANOTHER NOTION WHICH
IS IT IS NOT NECESSARILY THE
BEST ADJUTANT.
YOU NEED THE SIMPLEST
ADJUTANT, THE SIMPLE SOLUTION
SO IT GOES BACK TO WHAT PALO
SAID, THERE IS NOT A ONE SIZE
FITS ALL AND WHATEVER ADJUTANT
YOU HAVE NEEDS TO HAVE THE
BIGGEST IMPACT ON THE VACCINE.
THERE IS ANOTHER MODEL TO HAVE
IMPACT ON THE SOLUTION AND
THEN LOOK AT HAVING A STRONG
LEADERSHIP AND COMMITMENT TO
MAKE THE LOWER MARGIN
COUNTRIES COME ALONG SO TO
SPEAK SO THERE IS THIS VISION
AS WELL.
SO THE TECHNICAL MODEL AND
LEADERSHIP MODEL WOULD HELP IN
CREATING VACCINES.
>>THANK YOU, NICHOLAS, I
THINK THAT IS A GREAT POINT,
GREAT STATEMENT TO END THIS.
I WANT TO THANK THE PANELISTS
AND SPEAKERS FOR THEIR REMARKS
AND ANNIE, WE'LL HAND IT BACK
TO YOU.
>>OKAY, THANK YOU.
[INAUDIBLE] WE SHOULD TAKE A
FEW MINUTES BREAK [INAUDIBLE].
>>WE ARE GOING TO CONTINUE
WITH THE WEBINAR WITH SESSION
2 THAT IS TITLED SELECTION OF
ADJUVANT AND FORMULATION FOR
VACCINE R&D, RATIONAL OR
EMPIRICAL.
I HAVE CESAR BOGGIANO AND I
HAVE THE PRIVILEGE TO CONDUCT
THIS SESSION WITH ANA STAZIA
AGUILAR.
PLEASE GO AHEAD AS CO-CHAIR.
>>THANK YOU, A PLEASURE TO BE
WITH YOU HERE TODAY AND I AM
VERY HAPPY TO INTRODUCE THE
FIRST OF FOUR SPEAKERS, KEVIN
SAUNDERS, ASSOCIATED DIRECTOR
AT THE DUKE HUMAN VACCINE
INSTITUTE AND WILL BE TALKING
ABOUT MOLECULAR MECHANISM OF
ADJUVANTS AND HOW TO BEST
PRESENT TO IMMUNE SYSTEM.
>> THANK YOU, ANA STAZIA, I
WILL GO RIGHT AHEAD AND JUMP
IN SO WE CAN STAY ON TIME.
AT THE VACCINE INSTITUTE WE
ARE FOCUSED ON PRODUCING
ADJUTANTS FOR ANTIBODY
INFECTION.
AS YOU KNOW WE HAVE HAD
SEVERAL THREATS OVER THE LAST
TWO DECADES.
WHAT WE ARE TRYING TO DO IS
ELICIT NEUTRALIZING BODIES
WITH EXTREMELY HIGH
CROSS-REACTIVITY AGAINST A
VIRAL PATHOGEN.
TO PROMOTE THE AFFINITY
MATURATION OF ANTIBODIES WHICH
LEADS TO CROSS-REACTIVITY AND
ELICIT DURABLE AND HIGH
TITERS.
WE WANT THEM TO BE A CURB
RESPONSE OVER TIME AS WELL.
SO EARLY ON IN OUR WORK, WE
NOTICED THAT ADJUTANTS ARE
CRITICAL FOR INDUCING THESE
TYPE OF NEUTRALIZING
ANTIBODIES.
SO AS AN EXAMPLE, WE PRODUCED
A PRIMATE STUDY WHERE WE
ADMINISTERED THE VACCINE HERE
ON THE LEFT AND HAD A
NANOMECHANICAL PARTICLE AND
INTRODUCED THESE THREE TIMES
USING THE 3M052 ALUM, ALUM BY
ITSELF OR ANOTHER ADJUVANT.
AND WHAT WE FOUND IS IF YOU
DON'T INTRODUCE THE IMGENUINE,
YOU HAVE LESS OF A RESPONSE.
YOU CAN SEE WITH THE TITER ON
THE FIRST ONE, WE HAVE NO
RESPONSE.
WE CAN GET MORE WITH 3M WITH
AL LUM OR AL LUM BY ITSELF SO
WE KNOW GOING FORWARD THAT
ADJUTANTS ARE REALLY
IMPORTANT.
SO WE HAVE BEEN WORKING WITH A
GROUP AT UNIVERSITY OF
PENNSYLVANIA, MO HAMMED
GABRIEL, ANDY WISEMAN AND
PARTIES WHO ARE REALLY THE
ENGINEERS OF THE RNA PLATFORM.
WE ALSO CAME ACROSS THIS
OBSERVATION THAT THE LIP BID
NANOPARTICLES HAVE SOME
EFFECT.
SOME OF YOU MAY HAVE SEEN THIS
PUBLICATION THAT CAME OUT BACK
IN 2021 WHERE WE WERE LOOKING
AT THE ADJUTANT EFFECTS OF LMP
WHEN USED IN COMBINATION WITH
A PROTEIN AND THIS STUDY WAS
ABLE TO SHOW YOU CAN GET HIGH
TITERS OF ANTIBODIES IN THE
SERUM.
YOU CAN ALSO INCREASE THE
NUMBER OF PEOPLE PRODUCING
HELPER CELLS, PLASMA CELLS AND
OVERALL YOU CAN SEE THE MIX OF
PROTEIN CHOICE MADE A STRONG
ADJUTANT SYSTEM TO USE FOR THE
ANTIBODY RESPONSE.
THE SECOND THING WE WORKED ON,
YOU KNOW, YOU HAVE SEEN BOTH
MARS STUDIES AND OTHERS IN THE
FIELD WORKING ON HIV AND HAVE
FOUND THIS ADJUTANT CALLED
3M052 THAT COMES FROM THE 3M
COMPANY, YOU SEE AN AGO FIFTH
THAT INDUCES A DURABLE HIV
ENVELOPE WITH SPECIFIC PLASMA
CELLS AND HUMORAL IMMUNITY IN
NONHUMAN PRIMATES AND THIS IS
ONE OF THE ADJUTANTS WE ARE
LOOKING FORWARD TO WORKING
WITH IN OUR CLINICAL TRIALS.
SO WE ARE LOOKING AT BISHOP
MID NANOPARTICLES AS WELL AS
TLR AGO FIFTHS WHICH WE WOULD
LIKE TO MORE FORWARD AS PART
OF OUR ADJUTANT PORTFOLIO.
WE CURRENTLY HAVE PHASE 1
TRIALS WITH THE ENVELOPE AND
MIXED THEM WITH THESE TWO
TYPES OF ADJUTANTS AND COMPARE
THEM IN TRIALS TO SEE WHICH
GIVES YOU THE RESPONSE YOU
WANT IN THE CONTEXT OF THE
HUMAN IMMUNE SYSTEM.
SO HOW DO WE KIND OF GET TO
THESE DIFFERENT ADJUTANTS?
ONE OF THE THINGS WE LOOK AT
FIRST AND FOREMOST FOR OR HIV
PROGRAM IS WHAT IS THE
ADJUTANT THAT IS AFFECTED BY
THE IMMUNE GENUINE.
WE WANT TO DEFINE THE A TAPBT
FORMULATION THAT CAN TRANSLATE
FROM ANIMAL MODELS TO CLINICAL
AND AFFECT WHICH TYPES OF
ANTIBODIES WORK WITH YOUR ULP
MOON POPULATION.
WE ARE ALWAYS TRYING TO DEFINE
ADJUVANT OR ADJUVANT
FORMULATIONS THAT CAN
TRANSLATE FROM ANIMAL MODELS
TO CLINICAL USE.
SOMETIMES WE WILL COME ACROSS
ONE THAT LOOKS GREAT BUT THEN
WE WORRY WE COULD LOSE A LOT
OF THE PRIMATES IN THE CLINIC
SO BEFORE WE GET INTO A STUDY
WE CONSIDER WHETHER THIS
ADJUTANT IS SAFE ENOUGH TO GO
FORWARD.
WE ALSO WANT TO LOOK AT ARE
THERE ANNUAL TANS FIRST IN
HUMAN STUDIES THAT WERE
ALREADY COMPLETED, WAS THERE
REACTOGENICITY AND WAS IT
ACCEPTABLE AND MILD.
ONE OF THE QUESTIONS AROUND
3M-052 IS WHETHER IT WOULD BE
TOXIC IF DEVELOPED AND WHETHER
IT COULD BE USED WIDELY.
BY FORMULATING THIS IN TIER 2
NEUTRALIZING ANTIBODY TITERS.
SO WHAT WE DID WAS TAKE THE
SAME TWO ADJUVANTS, YOU CAN
SEE WITH THE TWO DIFFERENT
FORMULATIONS WE HAVE IDENTICAL
TITERS FOR BOTH.
SO IF WE HAVE A FORMULATION
THAT WE THINK MIGHT BE A SAFER
APPROACH FOR HUMANS, WE CAN
SWITCH OVER TO THAT ADJUVANT
IN OUR STUDIES AND ALSO IN OUR
CLINICAL TRIALS.
WHEN LOOKING AT ANIMAL MODELS
WE HAVE ALREADY LEARNED A
COUPLE OF LESSONS OVER THE
YEARS WE WANT TO MAKE SURE
THAT THE TARGETS ARE
APPROPRIATE FOR AN ANIMAL
SYSTEM AND IF WE WANT TO HAVE
A ANIMAL SYSTEM MODEL SYSTEM,
WE HAVE THE WE WANT TO MAKE
SURE IFS PREDICTIVE OF THE
HUMAN ANTIBODY RESPONSE.
SO LOOKING AT DIFFERENT TYPES
OF ANTIBODIES, IT MAY BE THAT
THAT IS NOT MADE IN AN
ACACANID OR A MOUSE.
IF THE ANIMAL MODELS ARE NOT
SUCH THAT YOU COULD USE THAT
SYSTEM, YOU HAVE TO TRY TO
FIND A DIFFERENT WAY TO TEST
THE ADJUTANT.
ONE OF THE WAYS WE CAME ACROSS
THIS IS WORKING WITH TL4 AGO
FIFTHS.
WE FOUND THEY WORK BEST IN THE
SMALL ANIMALS WE WERE USING
WITH THE ANTIBODIES THAT WERE
KNOCKED INTO THE MOUSE MODEL
SO WE THOUGHT THIS WAS A GREAT
WAY TO GO AND STARTED USING
THIS FOR OUR PRIMATE STUDIES
AS WELL.
HOWEVER, YOU CAN SEE ONCE WE
MOVED THE TLR4 AGO FIFTH, WE
FOUND IT IS WEAK COMPARED TO
THE TLR7/8 IN TIER 2.
WE TRIED TO UNDERSTAND WHY
THIS MIGHT BE.
WE FIRST LOOKED AT THE TITER
RESPONSES AND CYTOKINES AND
LOOKED AT 30 DIFFERENT KINDS
AND HOW THEY WERE ACTIVATED IN
THE IMMUNE SYSTEM.
WE DID NOT SEE ANY DETECTED
AFTER 24 HOURS AND IF YOU
COMPARE THAT TO THE
FORMULATIONS OF 3M-052, YOU
CAN SEE THE STABILIZED IN
ONE-THIRD AND THEN WITH THE
3M-052 WITH AL LUM, YOU SEE
MORE THAN A 50 PERCENT
CYTOKINE RESPONSE.
WHEN YOU GET DOWN TO THE BASIS
TO GOVERN THESE DIFFERENT
THINGS, YOU LEARN A LOT BEFORE
EXPRESSION OF THE TLR AND AS
YOU LOOK AT THE DIAGRAM TABLES
HERE AND LOOK ACROSS MONKEYS
AND HUMANS AND THE MOUSE,
THERE ARE DIFFERENT
EXPRESSIONS IN THE DIFFERENT
CELL TYPES WE WERE LOOKING AT.
WHAT WE THOUGHT WAS MOST
IMPORTANT WAS IN THE LIMPOID
CELLS, THE ADJUTANT WAS ABLE
TO ACTIVATE THE B AND T CELLS
BUT IN MONKEYS, THEY HAVE TO
BE ACTIVATED IN A CERTAIN WAY
BEFORE YOU CAN SEE EXPRESSION.
SO TARGETING B AND T CELL
RESPONSES WOULDN'T BE
EFFECTIVE IF WE USED THIS TYPE
OF ADJUTANT.
SO NOW I WILL SWITCH OVER AND
SAY QUICKLY AND TALK ABOUT
SOME OF THE STUDIES WE FOUND
WITH ANIMAL LIPID
NANOPARTICLES.
ONE OF THE MOST AMAZING THINGS
WE SAW EARLY ON IS IT
GENERATES EXTREMELY HIGH SERUM
TITERS AND YOU CAN SEE THE
MECHANICS HERE, THE NUMBER OF
TIMES IMMUNIZED.
ON THE NEUTRALIZATION TITER,
WE SEE IT APPROACHING ONE TO A
MILLION TITERS.
IF YOU COMPARE THAT TO SOME OF
THE TITERS I SHOWED YOU
BEFORE, IT WAS DOWN TO AROUND
1 TO 10,000 SO DEFINITELY
USING THE NAN MOW PARTICLE
WITH AN ADJUTANT IS HIGHER
THAN THE OTHER ONES WE USED.
WHEN WE LOOK AT THE RESPONSES
IN THE MONKEYS, YOU CAN SEE
THEY PROVIDE A REALLY HIGH PRO
CYTOKINE RESPONSE.
THIS WAS SOMETHING WE SAW IN
THE MOUSE STUDY AND THAT
SEEMED TO BE A CHATGPTMARK OF
THE LM NP WORKING AS THE
ANTIBODY IS COMING UP.
ALSO SEE IL-6 AND IL-18 DATA.
SO THESE ARE CRITICAL FOR
INDUCING THE BODIES WE'RE
TARGETING.
THE STABILITY AND ADJUTANT
STABILITY IS A CRITICAL ASPECT
TO CONSIDER.
SO IF YOU HAVE AN ADJUTANT
THAT STARTS DISRUPT THE
STABILITY OR CONFIRMATION, WE
KNOW THAT IS NOT ONE WE WANT
TO FOCUS ON.
WE HAVE TO CAREFULLY CONSIDER
THE STABILITY OF THE ADJUTANT.
WE HAVE THE ADJUVANT TARGET
EXPRESSION IN MODEL TELL
SYSTEMS NEEDED TO ENSURE
ADJUVANT PERFORMANCE.
WE ARE CURRENTLY INVESTIGATING
TLR7/8 AGO FIFTHS AND LIPID
NANOPARTICLES AS POTENT
ADJUVANTS IN HUMANS.
IT IS IMPORTANT TO TEST
FORMULATIONS THAT CAN BE
MANUFACTURED AND USED IN
HUMANS.
I WANT TO THANK THE LARGE TEAM
OF PEOPLE THAT WORKED ON THIS
INCLUDING OW PARTNERS AT AHI,
3M AND THE COMPANY WE WORK
WITH TO BE ABLE TO PRODUCE THE
LIPID NANOPARTICLES.
THE COLLABORATORS, WANT TO
MAKE SURE WE ACKNOWLEDGE
THOSE, THANK YOU.
>>THANK YOU, THAT WAS A GREAT
PRESENTATION.
THERE ARE A COUPLE OF
QUESTIONS IN THE CHAT ABOUT
NONNEUTRALIZING ANTIBODIES AND
I AM WONDERING IF YOU COULD
TRY TO ANSWER THOSE FROM THE
CHAT.
IF IT WILL TAKE TOO MUCH TIME
WE CAN MOVE ON BUT OTHERWISE
WE CAN COVER THOSE AT THE END.
SO THANK YOU SO MUCH.
FOR OUR SECOND TALK, SHANNON
MILLER, PROJECT MANAGER AT
IMMUNE CORP TALKING ABOUT THE
FORMULATION IMPACT ON VACCINE
PERFORMANCE.
THANK YOU, SHANNON.
>>ALL RIGHT, THANKS,
EVERYONE.
LET ME JUST GET MY SLIDES IN
FULL SCREEN MODE HERE.
>>GREAT.
>>SO HI, I AM SHANNON MILLER,
I WORK AT INIMMUNE AND THIS
TALK WILL BE FOCUSED ON
FORMULATION IMPACT ON VACCINE
IMMUNE RESPONSES.
THIS IS DONE IN COLLABORATION
WITH THE UNIVERSITY OF
MONTANA.
SO I THINK ONE THING THAT IS
SORT OF GOOD TO THINK ABOUT
WHEN WE THINK ABOUT THE
VACCINE, THE FORMULATION.
SO THE WAY I LIKE TO THINK
ABOUT THIS IS THE FORMULATION
IS KIND OF THE GLUE THAT HOLDS
THE ADJUTANT AND THE ANTIGEN
TOGETHER.
THIS CAN HAVE A LOT OF
DIFFERENT EFFECTS ON THE
IMMUNE RESPONSE THAT YOU GET
IN YOUR VACCINE SO
FORMULATIONS CAN AFFECT
WHETHER OR NOT ANTIGEN AND
ADJUVANT ARE CODELIVERRED,
CELLULAR UPTAKE AND
POST-INJECTION TRAFFICKING,
THE VACCINE STABILITY AND THE
COST AND COMPLEXITY OF
MANUFACTURING AND A SAFE
IMMUNE RESPONSE.
SO ONE CAVEAT I WANT TO BRING
UP IS THE LINE BETWEEN
ADJUVANT AND FORMULATION CAN
BE BLURRED.
YOU HAVE HEARD A LOT OF TALK
ABOUT LIPOSOMES WHICH ARE
ADJUVANTS THEMSELVES AND ALSO
FORMULATIONS SO SOME OF THE
FORMULATIONS THAT INDUCE
IMMUNE RESPONSES THEMSELVES
WITHOUT THE ADDITION OF AN
ADJUVANT AND IN THIS TALK, AN
ADJUTANT IS A SPECIFIC PATTERN
RECEPTOR AGO FIFTH.
SO YOU COULD CONSIDER THESE TO
BE COMBINATION ADJUVANTS OR
CONSIDER THEM TO BE
FORMULATION.
SO THAT IS KIND OF WHAT TENDS
TO BLUR THE LINE BETWEEN A
RANT AND FORMULATION.
OKAY, SO FOR THIS SLIDE, WE
WILL BE FOCUSING ON THREE
DIFFERENT ADJUVANTS IN
DEVELOPMENT AT INIMMUNE OR
UNIVERSITY OF MONTANA OR IN
COLLABORATION.
SO YOU HAVE HEARD ABOUT THE 3M
AGO FIFTH, THE TLR7/8 AND WE
WILL ALSO TALK ABOUT THE
MINUTECLE AGO FIFTH.
WE HAVE A LIBRARY OF MINCLE
ACTIVISTS AT THE UNIVERSITY OF
MONTANA AND CURRENTLY THAT AGO
FIFTH LIBRARY IS WHAT WE CALL
UM-1098.
SO WHEN WE THINK ABOUT
DESIGNING NEW ADJUTANTS FOR
VACCINES WE AT INIMMUNE AND UM
HAVE A SEPARATE SCIENCE GROUP
THAT THINKS ABOUT THESE FOR US
AND DAVE BURKEHART WHO IS MY
COLLEAGUE AT INIMMUNE WILL BE
GIVING A SHORT TALK LATER
ABOUT ADJUTANTS SO IF PEOPLE
WANT TO ASK TECHNICAL
QUESTIONS ABOUT FORMULATIONS
AND HOW EXACTLY THEY ARE
DEVELOPED AND MANUFACTURED,
THOSE ARE BETTER QUESTIONS FOR
HIM THIS.
BUT IMMUNE RESPONSE QUESTIONS
I CAN SPEAK TO.
SO ONE THING WE REALLY FOUND
WHEN WORKING WITH DIFFERENT
ADJUTANTS AND FORMULATIONS IS
THAT, AND THIS ONE IN
PARTICULAR, THE PATTERN
RESPONSE YOU WANT TO SEE.
IN PARTICULAR, WHEN YOU USE
1098 ADJUTANT FOR SAY A TUBES
VACCINE, IT IS VERY DEPENDENT
ON THE ADJUVANT.
WHEN YOU SEE THE IFN RESPONSE
AND THEN LOOKING AT THE
IL-17A, YOU SEE A HIGH IMMUNE
RESPONSE.
THIS SUGGESTS THERE ARE
CERTAIN PROPERTIES OR WAYS
THAT SNP IS DELIVERED FOR THE
ANTIGEN MAKING IT STRONG THAT
WE'RE NOT GETTING WITH THE
FORMULA -- FORMULATION.
YOU CAN SEE IT IS VERY STRONG
AND WHEN YOU LOOK AT THE OTHER
FORMULATION RESPONSES, THERE
IS NOT A LOT OF DIFFERENCE IN
THE RESPONSE.
[ GARBLED ]
WHEN YOU LOOK AT THE IGG
RESPONSES YOU START TO SEE
REALLY BIG RESPONSES DEPENDING
ON WHICH YOU CHOOSE FOR OUR
ANTIGEN.
KIND OF ALL OVER THE PLACE, IN
IGG1 WE SEE A STRONG IMMUNE
RESPONSE.
SO WHEN LOOKING AT IGG2C, IT
WAS VERY STRONG WITH
FORMULATION CHANGES WHERE THE
OTHERS WERE LESS RESPONSIVE TO
OUR FORMULATION CHANGES.
I WANT TO SWITCH GEARS A
LITTLE BIT AND TALK ABOUT OUR
I UM-1098 ADJUTANT, WE FOUND
IT TENDS TO PRODUCE A REALLY
STRONG HA AND 4001 RESPONSE.
SO WITH THE PURIFIED
INFLUENZA, YOU GET THIS NICE
REALLY CLEAR FORMULATION
SUGGESTING THE PH RESPONSE.
WE FOUND INCORPORATING 4001 IN
DIFFERENT TYPES OF SYSTEMS
COULD GET YOU THAT RESPONSE
YOU WANTED WHILE KEEPING THE
INDUCTION OF 4001 ITSELF.
SO IF YOU LOOK HERE AT THE
IL-5 RESPONSE, THESE LIPOSOMES
ARE ALL GIVING THE RESPONSE
WITH ANTIGEN ALONE AND WHEN
YOU ADD 4001 IN THE
FORMULATION, INSTEAD OF THE
FORMULATION YOU SAW WITH THE
NONRESPONSE, YOU MAINTAIN THE
IL2 RESPONSE WITH ALSO A
STRONG RESPONSE IN HA AND
4001.
WE ALSO USE A STRONG IL GG2A
RESPONSE, YOU CAN SEE THE
RESPONSE WITH THE FORMULATION.
THERE ARE ALSO REALLY
INTERESTING DIFFERENCES
BETWEEN DIFFERENT ADJUTANTS
AND HOW THE SAME FORMULATION
CAN CHANGE THE RESPONSE OF
THAT ADJUTANT.
SO IN THIS CASE, WE FOUND THAT
DIFFERENT HEMULSION
FORMULATIONS CAN ENHANCE THE
20,002 DRIVEN RESPONSE BUT NOT
THE 4001 FOR TLR7/8 SO THEY DO
NOT ACTIVATE THE IL-17A.
SO IN THIS CASE WE WERE USING
BOTH ANTIGENS IN COMBINATION
WITH THE SAME ADJUVANT AND YOU
CAN SEE EACH ONE, 4001 OR 2002
RAY LONE, KIND OF A MINIMAL
VARIATION, IL-17 SEEING IS
RESPONSE BY ITSELF AND WHEN WE
ADD THE ADJUTANT OR THE
EMULSION ANTIGEN, YOU SEE A
SIGNIFICANT RESPONSE TO THE
IMMUNITY BUT WHEN ADDING
EMULSION2, YOU SEE A VERY LOW
RESPONSE.
BUT WE SEE A STRONG
ENHANCEMENT OF THE IL-17
RESPONSE THAT YOU DON'T SEE
WITH INI-4001 SO THIS KIND OF
MAKES THE CASE WITH THINKING
ABOUT FORMULATIONS AND KINDS
OF ADJUVANTS IN AND OF
THEMSELVES BECAUSE CLEARLY,
SORRY, THERE IS SOME SORT OF
COMBINATION RESPONSE GOING ON
WITH THIS EMULSION AND
INI-2002 THAT WE DON'T SEE
WITH 4001.
SO THEN YOU CALCULATE THE
ENERGY GOING ON HERE THAT MAY
BE UNIQUE TO 2002 OR 2004 AGO
FIFTH IN GENERAL.
INTERESTINGLY, WE HAVE ALSO
FOUND THAT OCCASIONALLY WE
WILL MAKE A FORMULATION CHANGE
FINANCIAL OFFICER WHATEVER
REASON, NOT GETTING THE IMMUNE
RESPONSE WE WANT, DON'T GET
THE STABILITY OF OUR
FORMULATION, WE WANT TO SEE,
YOU KNOW, A DIFFERENT TYPE OF
A IMMUNE RESPONSE, SO WE'LL
MAKE AM ALTERATIONS TO OUR
FORMULATION THAT WE THINK
PROBABLY WON'T HAVE MUCH OF AN
EFFECT ON OUR IMMUNE RESPONSE
AND WHAT WE ARE SEEING
SOMETIMES IN PARTICULAR WITH
COMBINATION ADJUVANT
APPROACHES, WE WILL FIND A
BODY RESPONSE WITHOUT
AFFECTING OUR T CELL RESPONSE
WHICH IS REALLY INTERESTING
SUGGESTING THAT SOMEWHERE
ALONG THE LINE WE SUPPORT TO
AN EXTENT THE T CELL RESPONSE
AND ANTIBODY RESPONSE WHERE
YOU MIGHT TEND TO THINK THOSE
TWO GO TOGETHER WHEN THINKING
ABOUT ANTIBODY RESPONSES AND
CYTOKINE PRODUCTION FROM T
CELLS.
SO IN THIS CASE WHAT WE'RE
LOOKING AT IS THE SYNTHETIC
ADJUVANT SYSTEM, OUR 2002 WITH
SAPONIN SO WE ARE LOOKING AT A
DIFFERENT ANTIGEN THAN WE WERE
LOOKING AT BEFORE, WHICH IS A
DETERGENT-SPLIT VACCINE AND
THIS IS MON OVALENT.
SO WHEN WE MIX THE ADJUVANT
WITH THE ANTIGEN, YOU CAN SEE
WE ARE STARTING TO RESPOND IN
THE IGG2A ANTIBODY TITERS
WHERE IGG1 IS CONSISTENT.
THEN ADDING THE ANTIINFLUENZA
TITER, YOU DON'T SEE WHAT YOU
WOULD EXPECT IN THE T CELL
RESPONSE HERE WHEN WE CHANGE
THE LIPOSOMAL RESPONSE AND WE
CURRENTLY DON'T SEE ANY
CHANGES IN OUR R2H2 WITH
ANTIBODY PRODUCTION.
SO I KNOW THIS TALK WAS
FOCUSED ON ADJUTANT TESTING OR
IS THERE ANY KIND OF
MODIFICATION WE CAN DO.
IN OUR HANDS, HAVING WORKED
WITH MANY, MANY DIFFERENT
ADJUVANTS, ANTIGENS AND
DIFFERENT FORMULATIONS, IT
TURNS OUT IT IS KIND OF A
COMBINATION OF THE TWO.
SO ADJUTANTS TEND TO HAVE
SPECIFIC PROPERTIES, RIGHT?
ESPECIALLY IF THEIR PATTERN
RECOGNITION AGO FIFTH, WOULD
HE KNOW WHAT TARGET THEY ARE
PREDICTING AND THE RESPONSE WE
CAN EXPECT.
THE SAME IS TRUE FOR ADJUVANT
FORMULATIONS OR FOR SOME
ORGANIZATIONS.
OBVIOUSLY WE HAVE NOT YET
EXPLORED THE FULL SORT OF
REPERTOIRE OF ALL FORMULATIONS
THAT COULD EVER BE USED BUT WE
DO KNOW SOME THINGS.
SO FOR EXAMPLE, THERE'S QUITE
A FEW PUBLICATIONS THAT TELL
US A CODELIVERY OF ADJUTANT
AND ANTIGEN ARE PRETTY
IMPORTANT ESPECIALLY FOR T
CELL RESPONSES, PH 1 AND T
CELL RESPONSES IN PARTICULAR.
THERE ARE ALSO PUBLICATIONS
OUT THERE TELLING US ABOUT HOW
FORMULATIONS, WHEN YOU USE A
FORMULATION IN A SACKS
VACCINE, YOU TYPICALLY GET A
PRETTY UNIFORM CLINICAL SIZE
CHARGE, SHAPE, FOR A PROPERTY
CALLED FPHOSPHORUS AND THESE
OVER TIME CAN BE PREDICTED
ALTHOUGH NOT ALWAYS BECAUSE AS
WE ALSO HEARD OR SAW, WHEN WE
ADD THE ANTIGEN OR CHANGE THE
ANTIGEN, ALL OF THESE
PROPERTIES CAN THEN CHANGE.
THE COMBINATION OF ADJUTANT
AND FORMULATION EXCIPIENS CAN
RESULT IN UNEXPECTED IMMUNE
RESPONSES WHICH WE SAW IN THE
2002 AND ILG17 RESPONSE.
ANOTHER IMPORTANT THING TO
MENTION IS SPECIES
SPECIFICITY.
SO WILL THOSE RESPONSES MEAN
ANYTHING DOWN THE LINE WHEN WE
TRY TO LOOK AT HUMAN
RESPONSES?
WHAT WE FOUND IS THAT SIMILAR
RESPONSES IN A NUMBER OF
ANIMAL MODELS CAN INCREASE THE
CONFIDENCE THAT ALL OF THESE
DATA WILL TRANSLATE TO HUMANS.
SO WITH THAT, I WOULD LIKE TO
THANK EVERYONE AT INIMMUNE AND
UNIVERSITY OF MONTANA.
MY COLLEAGUE IS GIVING A TALK
LATER AND LEADS THE
FORMULATION GROUP WITH
SPECIFIC TECHNICAL QUESTIONS
ABOUT THAT SHOULD BE DIRECTED
AT HIM.
THANKS AND I WILL ANSWER
QUESTIONS IF WE HAVE TIME.
>>THANK YOU, YEAH, UP
FORTUNATELY WE DON'T BUT WE
DEFINITELY AGREE FORMULATIONS
ARE THE MOST IMPORTANT THING.
[LAUGHTER]
[INDISCERNIBLE]
[OVERLAPPING SPEAKERS]
>>AND WE WILL SAVE THE
QUESTIONS FOR YOU FOR PANEL
DISCUSSION.
AND NOW WE WILL BRING IN THE
NEXT TWO SPEAKERS.
>>ABSOLUTELY, THANK YOU, ANA.
WE WILL INTRODUCE
JOSPHAT KOSGEI AS PRINCIPLE
INVESTIGATORS WITH THE U.S.
ARMY MEDICAL RESEARCH UNIT IN
KENYA AND HE WILL BE TALKING
ABOUT ADJUVANT PERFORMANCE IN
TARGET POPULATIONS, RV 460 HIV
VACCINE TRIAL IN KENNA I
CAN'T.
>>THANK YOU VERY MUCH, GOOD
MORNING AND EVENING AS WELL, I
BELIEVE YOU CAN HEAR ME?
>>WE CAN HEAR YOU WELL.
>>THANKS.
OKAY, IS THIS IN PRESENTATION
MODE?
>>THAT LOOKS PERFECT AND YOU
SOUND PERFECT, GO AHEAD.
>>OKAY, THANKS FOR THE
ABILITY TO TALK TO YOU ABOUT
ADJUVANT PERFORMANCE IN TARGET
POPULATIONS IN KENYA.
SO THIS STUDY INITIATED IN
MARCH 2021 WITH THE PRIMARY
OBJECTIVE TO ASSESS SAFETY,
REACTOGENICITY AND
TOLERABILITY OF THE VARIOUS
ADJUVANT FORMULATIONS WITH
BOTH HIV ENV PLAS MID DNA AND
GP145.
THE SECOND SECONDARY
OBJECTIVES ARE TO DETERMINE
WHETHER THE ADJUVANTS IMPROVE
THE IMMOONOGENICITY OF DNA
PRIMING, DETERMINE WHETHER THE
ADDITION OF ALF43 PROTEIN
BOOSTS FURTHER OR IMPROVES
IMMUNE RESPONSE TO GP145 AND
DETERMINE WHETHER ADJUVANTS
IMPROVE HUMORAL RESPONSES.
EVALUATE THE INFLUENCE OF
ADJUVANT AND CAN IT IMPROVE
DNA PRIMING AND FURTHER
IMPROVE PROTEIN BOOSTING.
AT THIS TIME, WE LOOK AT THE
ENV-CPLASMID DNA AND COMPARE
WITH GP145 AND HERE YOU SEE A
MICRO GRAM WITH THE IMGENUINE
AND OF COURSE THE OTHER
AVAILABLE ADJUVANTS AVAILABLE.
[INDISCERNIBLE]
SO THE TRIALS INTRODUCED, I
THINK ON THIS ONE, IT WAS NOT
POSSIBLE ON DNA ALONE, THEN WE
USE REHYDRAGEL AS THE PLACEBO.
AND THIS ONE HERE, WE HAVE THE
THREE IN THERE AND THEN FOR
THE BOOSTER, THE REHYDRAGEL
ALONE OR THESE TWO OR THREES
THREE AND THE TRANSMISSION WAS
THE SAME.
FOR THIS, WE HAVE THE
COMBINATION SO WE HAVE THREE
OVER TIME AND FOLLOWED THE
PARTICIPANTS FOR 108 WEEKS,
105 WEEKS OF CLINIC VISITS AND
THEN CONTACTED BY PHONE ONCE
WEEKLY FOR ADDITIONAL THREE
WEEKS TO INQUIRE ABOUT
MEDICALLY ATTENDEDS.
SO WE LOOK AT THE OPTIONAL
PROCEDURES, INGUINAL LYMPH
NODE.
SO FOR SCREENING AND
ENROLLMENT, WE LOOK AT THE
MALE AND FEMALE, MEDIAN AGE OF
30 YEARS, MOST OF THEM WERE
FEMALE, AND MOST WERE SINGLE,
NEVER MARRIED AND OCCUPATION
RANGED BY LARGEST WAS FARMER.
SO WE LOOKED AT THIS IN THE
POPULATION AND ALL VACCINES
WERE COMPLETED SO NOW IN
CLINICAL FOLLOW UP VISITS
CONCLUDING IN JANUARY 2024
NEXT YEAR.
SO THE SYMPTOMS OF THE PRIME
AND BOOST VACCINES INCLUDE
PAIN AND TENDERNESS, SWELLING
AND INDURATION, REACTION AT
THE SITE.
SO THESE ARE WHAT WAS REPORTED
AND NEARLY HALF OF THE
PARTICIPANTS DID NOT RECEIVE
ANY SYSTEMIC REACTION.
SO IF GENERAL, THIS PROTOTYPE
HAS BEEN WELL TOLERATED.
THERE IS NO REACTOGENICITY AND
TOLLABILITY OF VACCINE HAS
BEEN EXCELLENT, THERE WAS NO
SEVERE OR LIFE-THREATENING
LOCAL INJECTION OR SYSTEMIC
REACTIONS, THERE WAS ONE
SERIOUS ADVERSE EVENT FOR NEW
ONSET TYPE 1 DIABETES IN A
23-YEAR-OLD FEMALE THAT WAS
UNRELATED TO THE STUDY AND TWO
POTENTIALLY REACTIONS.
SO WE FOCUS ON DNA PRIME
VACCINATIONS WITH DNA ALONE,
ADDING DMLT, ALF43 AND THEN
USING BOTH.
AS YOU CAN SEE THE RESPONSES,
THERE WAS SIGNIFICANTLY HIGHER
RESPONSE RELATED TO THE DMLT
AND THE PROTEIN AS SEEN HERE.
AND THEN ADDING THE GP145
PROTEIN, YOU CAN SEE THE
RESPONSE.
SO YOU CAN SEE IN GROUPS 6 AND
GROUP 7 THERE WAS HIGHER
RESPONSES.
SO IN GENERAL, THIS IS TO SAY
THAT THE RESPONSES TO DMLT AND
THIS IS THE VISIT AFTER THE
PRIME BOOST IN 30 PERCENT OF
PARTICIPANTS.
AND IN GROUP 7, THESE PEOPLE
INCLUDE THE HIGHEST ANTIBODY
BINDING RESPONSES.
GROUPS 5 THROUGH 7 ALSO
BETWEEN RATED HIGHER,
CROSS-CLADE ANTIBODY RESPONSES
AGAINST GP140 HIV ANTIGENS
COMPARED TO GROUPS THAT
RECEIVED DNA ALONE.
AND ALSO HERE THE
COADMINISTRATION OF LIPOSOMAL
ADJUVANT ALF43 ALONG WITH
HIV-1 DNA VACCINE IMPROVED
BINDING RESPONSES AGAINST
HIV-1.
SO YEAH, THAT IS THE WORK WE
ARE CURRENTLY DOING.
IT IS A WORK IN PROGRESS AND I
WILL FOLLOW UP IF THERE ARE
ANY QUESTIONS.
THANK YOU VERY MUCH.
>>THANK YOU VERY MUCH,
JOSPHAN KOSGEI.
FASCINATING STUDY AND I LOOK
FORWARD TO SEEING THE FINAL
RESULTS OF THE DATA.
SO WE WILL MOVE TO THE NEXT
PRESENTATION BY MARION GRUBER
WHO IS VICE-PRESIDENT OF
PUBLIC HEALTH AND REGULATORY
SCIENCE WITH THE INTERNATIONAL
AIDS VACCINE INITIATIVE AND
WILL DISCUSS REGULATORY
CONSIDERATIONS FOR ADJUVANTS.
TAKE IT AWAY.
YOU ARE STILL MUTED.
>>OKAY, CAN SEE THE
PRESENTATION?
>>WE CAN HEAR YOU AND SEE
YOUR PRESENTATION PERFECTLY,
GO AHEAD.
>>VERY GOOD.
YEAH, THANK YOU VERY MUCH FOR
THE INTRODUCTION.
I WAS ASKED TO GIVE THE
REGULATORY CONSIDERATIONS
REGARDING FORMULATING VACCINES
WITH AIDS VACCINE AND THESE
HAVE BEEN CREATED USING TWO
SPECIFIC ADJUVANTS TO DEVELOP
THE IMMUNE RESPONSE TO VACCINE
ANTIGENS.
AND THESE ANTIGENS MAY REQUIRE
THE PRESENCE OF ADJUVANTS TO
ENHANCE THE IMMUNE RESPONSE TO
VACCINE ANTIGENS, REDUCE
DOSING FREQUENCY, INDUCE
CROSS-PROTECTIVE INFECTION AND
DIRECT THE IMMUNE RESPONSE AND
OR ACHIEVE ANTIGEN SPARING.
LIKE FOR EXAMPLE THE VACCINES
IN UNITED STATES AND EUROPE
THAT CONTAINS ALL THE
ADJUVANTS AND IN THE INTEREST
OF TIME, I WILL NOT WALK
THROUGH EACH OF THESE BUT THIS
SLIDE SHOWS THE EXAMPLES.
SO TO MAKE A A LONG STORY
SHORT, THE ADJUVANTED VACCINES
DEVELOPMENT STRATEGY, IT IS
NOT ANY DIFFERENT THAN FOR
VACCINES THAT WERE NOT
FORMULATED AND THERE ARE SOME
CONSIDERATIONS I WILL BE
DISCUSSING IN A COUPLE OF
MINUTES.
SO BASICALLY, AND THIS IS VERY
HIGH LEVEL, THE DATA TO
SUPPORT THE CLINICAL STUDIES
AND FOR THE VACCINE, YOU
CONDUCT THE PLAN AND TEST THE
SAFETY OF THE PRODUCT.
OF COURSE THE GOAL IS TO HAVE
A SAFE EFFECTIVE HIGH QUALITY
PRODUCT OF KNOWN STABILITY
THAT CAN BE CONSISTENTLY
MANUFACTURED.
SO THAT IS NO DIFFERENT FROM
OTHER VACCINES THAT DO NOT
CONTAIN ADJUVANTS.
WHY CAN I NOT -- I'M SORRY.
OKAY, I MENTIONED SOME SPECIAL
CONSIDERATIONS SO ADJUVANTS
REQUIRE SPECIAL
CONSIDERATIONS, AND CAN
INCLUDE COMBINATIONS OF
SUBSTANCES USED IN CONJUNCTION
TO VACCINE ANTIGEN TO ENHANCE
VACCINE RESPONSE.
THEY EXHIBIT A RANGE OF
PROPERTIES THAT INVOKE COMPLEX
IMMUNE RESPONSE AND WHAT WE
HEARD EARLIER THIS MORNING IS
THAT ANIMAL MODELS THAT
PREDICT SAFETY AND EFFICACY OF
ADJUVANT-ANTIGEN COMBINATIONS
ARE NOT ALWAYS AVAILABLE.
SO TO HELP THE VACCINE
DEVELOPER OUT, THERE ARE A
NUMBER OF EVALUATIONS AND THIS
ONE IS CALLED FRAMEWORK FOR
ASSESSMENT OF ADJUVANTED
VACCINES.
AND THIS GUIDELINE IS BY
NATIONAL REGULATORY AUTHORITY
INCLUDING FDA AND EMA.
AND WHEN I WAS AT FDA, THIS
WAS PART OF THE GUIDE
SUPPLEMENT.
SO IN SHORT, IT DESCRIBES THE
QUALITY, PHARMACOLOGICAL,
TOXICOLOGICAL AND OTHER
INFORMATION NEEDED TO SUPPORT
THE INITIATION OF CLINICAL
TRIALS WITH THE VACCINE
COMBINED WITH A NOVEL
ADJUVANT.
IT PROVIDES CONSISTENT AND
HARMONIZED GUIDANCE ON
NONCLINICAL TESTING APPROACHES
TO SUPPORT USE OF CANDIDATE
ADJUVANTED VACCINES IN ALL
STINGS OF CLINICAL DEVELOPMENT
AND DESCRIBES DESIGN ELEMENTS
FOR FIRST-IN-HUMAN CLINICAL
TRIALS.
HOWEVER, MANY NRAS PROVIDE A
REGULATORY AND LEGAL
CLASSIFICATION FOR ADJUVANT
COMPONENT OF VACCINE, THAT CAN
BE EXCIPIENT, ACTIVE
INGREDIENT OR CONSTITUENT
MATERIAL, DEPENDING ON THE
PARTICULAR DEFINITION USED BY
THE PARTICULAR NRA AND
ADDITIONAL TESTING MAY BE
REQUIRED.
SO TAKE THE OS FDA REGULATORY
DEFINITION AND CONSIDERATION
ON ADJUVANTS.
THE FDA SAYS ADJUVANTS ARE NOT
CONSIDERED ACTIVE INGREDIENTS
AND THEN THERE IS CONSTITUENT
MATERIAL SO THERE IS NO
VACCINE ADJUVANT ON ITS OWN
THAT COULD BE PICKED SO IT IS
ONLY COMPONENT OF PARTICULAR
ADJUVANTED VACCINE AND IT IS
THE ARE ADJUVANTED VACCINE
FORMULATION IN TOTO THAT IS
TESTED IN CLINICAL TRIALS AND
LICENSED.
OF COURSE THE ADJUVANTED
VACCINE FORMULATION MUST BE
SAFE AND EFFECTIVE AND
BENEFITS OUTWEIGH ITS RISK.
SO WE LOOK AT THE STEPS ONE
HAS TO GO THROUGH TO ENSURE
THE QUALITY AND SAFETY.
THERE IS OFTEN COMBINATION OF
COMPONENTS WITH TOO MUCH DATA
TO PERFORM SAFE STUDIES SO
THEY START USING ANIMAL TRIALS
AND USUALLY START WITH
CLINICAL TRIALS TO IDENTIFY
AND CHARACTERIZE POTENTIAL
LOCAL AND SYSTEMIC ADVERSE
EVENTS THAT MAY OCCUR IN THE
MODEL AND ALSO A FULL TISSUE
LIST FOR NOVEL ADJUVANTS.
THIS FRAMEWORK OR GUIDELINE
ALSO WILL TALK ABOUT AT WHAT
STATE REPRODUCTIVE TOXICITY
TESTING SHOULD BE DONE.
CONDUCTED IN PARALLEL WITH
PHASE 3 CLINICAL TRIALS FOR
PRODUCTS INTENDED FOR USE IN
FEMALES OF CHILD BEARING AGE
AND WHEN AND HOW SHOULD THE
ADDED BENEFIT OF ADJUVANT BE
DEMONSTRATED?
THE MANUFACTURER SHOULD
PROVIDE RATIONAL FOR USE OF
ADJUVANT IN VACCINE
FORMULATION.
IT CAN BE PRECLINICAL STUDIES
OR PROOF OF CONCEPT STUDIES IN
ANIMAL TRIALS.
IT COULD ALSO DEMONSTRATE WHAT
CAN HAPPEN WHEN COMPARING
ADJUVANTED VERSUS UNADJUVANTED
VACCINES WITH POLYMERS AND CAN
INCLUDE EVIDENCE OF LOOKING
FOR ENHANCED IMMUNE RESPONSES,
ANTIGEN SPARING EFFECTS OR
OTHER ADVANTAGES AND OF COURSE
LOOKING AT THE INFORMATION OF
PRESUMED MECHANISM OF ACTION
OF ADJUVANT IN AVAILABLE.
I MENTIONED BEFORE THAT THE
ADJUVANTS ARE NOT CONSIDERED
ACTIVE INGREDIENTS FROM A
REGULATORY PERSPECTIVE SO
MANUFACTURERS ARE NOT REQUIRED
TO DEMONSTRATE THE ADDED
BENEFIT OF AN ADJUVANT IN
COMPARATIVE PHASE 3 EFFICACY
AND SAFETY TRIALS.
SO WE LOOK IT STUDIES
COMPARING VACCINE ANTIGEN WITH
AND WITHOUT ADJUVANT HOWEVER
NEVER SAY NEVER BECAUSE THEY
MAY BE REQUESTED ON A
CASE-BY-CASE BASIS.
FOR EXAMPLE, IF A MANUFACTURER
WANTS TO MAKE A PRIORITY CASE,
AFTER THE SAFETY CONCERNS HAVE
BEEN IDENTIFIED AND THEN THE
MANUFACTURER WILL INCLUDE THE
SUPERIORITY CLAIMS AND THEN IT
MAY BE USED.
SO WE REALLY CALL IT PARAMOUNT
WHEN ANTIBODY ADJUVANTS ARE
DEVELOPED.
THERE ARE SPECIAL
CONSIDERATIONS FOR CLINICAL
SAFETY EVALUATION AND ANY
ADJUVANT TO ANY VACCINE
FORMULATION NEEDS TO BE TESTED
AND BALANCED WITH THE RISK OF
ADVERSE REACTIONS.
SO WHAT THEY DO EARLY IN PHASE
1 OR 2 STUDIES, THEY COMPARE
THE VACCINES WITH SALINE
PLACEBO WHICH IS STABLE OR THE
ADJUVANTED VACCINE VERSUS THE
UNADJUVANTED ANT ANTIGEN.
AND THERE ARE SPECIFIC
INQUIRIES REGARDING SYMPTOMS
CONSISTENT WITH AUTOIMMUNE AND
NEUROINFLAMMATORY DISEASES.
LONGER POST-VACCINATION FOLLOW
UP IS TYPICAL FOR
NONADJUVANTED VACCINES.
TYPICALLY IT IS 12 MONTHS
FOLLOWING VACCINATION BUT IT
COULD BE LONGER AND SAES WILL
ASK ARE THERE ANY NEW ONSET
MEDICAL CONDITIONS OR ADVERSE
EVENTS OF SPECIAL INTEREST
POPPING UP AS YOU FOLLOW THE
SUSPECT.
SO THE SAFETY EXPERIENCE WITH
THE SAME ADJUVANT FORMULATION
WITH OTHER VACCINE ANTIGENS
MAY CONTRIBUTE AND MAY SUPPORT
THE SAFETY OF A NEW VACCINE
ANTIGEN FORMULATED WITH THE
SAME ADJUVANT.
AGAIN, JUST QUICKLY, WITH
VACCINE FOLLOW UP, THERE IS A
LOT OF CONCERN BECAUSE ON THE
ONE SIDE, SOME POTENTIAL
ADVERSE EVENTS BEGINNING AFTER
VACCINATION MAY NOT BE
RECOGNIZED OR DIAGNOSED TILL
MUCH LATER.
SO THERE IS A TRADE-OFF.
A LONGER DURATION CAN INCREASE
IDENTIFICATION OF POTENTIAL
AES BUT MAY INCREASE NOISE,
RIGHT?
SO LONGER FOLLOW UP IS OFTEN
ROUTINELY OBTAINED IN EFFICACY
STUDIES BUT THEY MAY NOT SOME
SYMPTOMS MAY HAVE NOTHING TO
DO WITH THE VACCINE
COMBINATION.
NOW, IF THE LONGER FOLLOW UP,
THERE ARE VACCINES THAT ARE
EVALUATED FOR IMMUNEOGENICITY
AND THEN OF COURSE YOU DON'T
HAVE TO DIG INTO STUDIES OR DO
OTHER FOLLOW UPS SO THOSE CAN
PREDICT THE SAFETY STEPS WITH
VACCINE POPULATIONS.
THE AESI OR ADVERSE EVENTS OF
SPECIAL INTEREST FOCUS ON
AUTOIMMUNE, INFLAMMATORY
DISEASES, NEUROINFLAMMATORY
DISORDERS, MUSK LOW SKELETAL
AND CONNECTIVE TISSUE DISEASES
AND GI DISORDERS.
SO IN SUMMARY, REGULATORY
PATHWAYS SUPPORTING
DEVELOPMENT AND APPROVAL OF
VACCINES FORMULATED WITH NOVEL
ADJUVANT ARE THE SAME AS FOR
UNADJUVANTED VACCINES.
EFFICIENT PLANNING OF
DEVELOPMENT PATHWAY FOR ANY
ADJUVANTED VACCINE REQUIRES
CAREFUL ATTENTION TO
PRECLINICAL TESTING, STUDY
DESIGN, DOSING DECISIONS AND
SAFETY MONITORING AND AGAIN
ALTHOUGH MANUFACTURES ARE NOT
REQUIRED TO DEMONSTRATE THE
ADDED BENEFIT OF ADJUVANTED
VERSUS UNADJUVANTED VACCINES
IN CLINICAL COMPARATIVE PHASE
3 STUDIES, MANUFACTURERS
SHOULD PROVIDE A JUSTIFICATION
FOR INCLUDING AN ADJUVANT IN
THE VACCINE AND EVALUATION OF
SAFETY OF AN ADJUVANTED
VACCINE NEEDS TO INCLUDE
SPECIAL STATE CONSIDERATIONS
AND THAT CONCLUDES MY TALK AND
THANK YOU VERY MUCH FOR BEING
ABLE TO PROVIDE THIS
PERSPECTIVE.
>>THANK YOU VERY MUCH,
MRS. BRUBER, THAT WAS A VERY,
VERY INTERESTING TALK AND
QUITE INFORMATIVE.
NOW WE WILL GO TO OUR PANEL
AND I WILL START WITH ANA.
>>WE WILL START WITH THE
QUESTION OF COMPUTATIONAL
METHODS FOR OPTIMIZING OR
DESIGNING ADJUTANTS, DOING A
GREAT JOB OF IMMUNE OR SAFETY
DESIGNS AND THE PATHWAYS THE
DELIVERY CAN HAVE AND BECAUSE
THEY TEND TO SPIRAL OUT OF
CONTROL WE HAVE TO SET SOME
BUDGET OR REQUIREMENTS.
SO DO YOU HAVE ANY WAY TO
OPTIMIZE THESE, DO YOU FEED
THESE INTO THE BILL OR TO YOU
JUST TAKE A STAB AT IT?
>>DEFINITELY AT THE
UNIVERSITY OF MONTANA, THE
RESEARCHER THERE HAS STARTED
TO TRY TO TACKLE THIS BY
ANALYSIS OF THE LIMP NODES
PRE- AND POST INJECTION AND
TRYING TO BUILD A DATABASE TO
DIFFERENT IMMUNE RESPONSES IN
A BROADER SENSE.
I KNOW THEY ARE EVALUATING
VACCINES ON AND PEOPLE CAN GO
AND LOOK UP DIFFERENT
ADJUTANTS TO SEE WHAT KIND OF
IMMUNE RESPONSE THEY GIVE BUT
WE KNOW THERE ARE SO MANY IN
RESPONSE WITH TWO OR THREE
ADJUVANTS THAT ARE GIVING THE
RESPONSE WE HAVEN'T PICKED UP
ON YET.
SO THERE ARE SUBTLE
DIFFERENCES WE WILL NOT PICK
UP TILL WE HAVE A DATABASE OF
RESPONSES AND UNTIL WE HAVE
THAT, IT WILL BE HARD TO
PREDICT WHICH ADJUVANTS AND
FORMULATIONS PAIR WELL
TOGETHER.
>>ANYONE ELSE WITH THOUGHTS?
IF NOT I CAN MOVE ON TO
ANOTHER QUESTION.
>>SO I CAN MOVE AHEAD WITH
THE NEXT QUESTION.
SINCE MANY OF OUR VACCINES ARE
TRYING TO GAUGE THE CORE OF
RESPONSE FROM PROJECTION OF
ENTRY, SO.
[INDISCERNIBLE]
SO THE QUESTION FOR EVERYBODY
IS HOW MUCH YOU TAKE INTO
CONSIDERATION FOR CLINICAL AND
ANA STAZIA, I KNOW YOU HAVE A
CLINIC AND I WOULD LIKE TO
HEAR YOUR THOUGHTS ABOUT IT.
>>YES, THANK YOU VERY MUCH.
THIS IS REALLY IMPORTANT FOR
THE GROUP TO KNOW WHAT
ANTIBODY OR IMMUNE RESPONSE SO
WHEN THE PARTICIPANTS, LOOKING
AT ADJUTANTS IN THESE CASES,
THE ONES PROVIDED TO THE
PARTICIPANT AND MEASURED
IMMUNE RESPONSE SO AT THE END,
WE WERE SEEING A GOOD IFP BUT
BECAUSE IT TAKES SOME TIME TO
HAVE MORE SPECIFICS AND FOLLOW
UP ON THOSE SO AGAIN --
[INDISCERNIBLE]
>>AND KEVIN, YOU HAVE ANY
REPORTS ON THE CLINICAL SIDE,
HOW MUCH SAMPLING OR
CONSIDERATION IS GIVEN TO
THAT?
>>SURE, I WILL JUST JUMP IN
REAL QUICK.
SO YES I THINK PARTICULARLY
FOR VIRUSES LIKE CORONA
VIRUSES OR INFLUENZA, WE'RE
REALLY FOCUSED ON MUCOSAL
RESPONSES SO FOR THOSE STUDIES
WE'RE LOOKING AT THE UPPER
RESPIRATORY AND LOWER
RESPIRATORY TRACT AND THE
STUDIES ARE NOT CONSIDERED
COMPLETE UNLESS YOU DO THAT SO
WITH SOMETHING LIKE HIV WHERE
WE LOOK AT SEC CREASES AND
RECTUM SWABS, MUCOSA RESPONSES
ARE IMPORTANT THERE TOO.
SOMETIMES IT IS DIFFICULT TO
SAMPLE THOSE LONGITUDINALLY
BECAUSE THEY ARE ALWAYS
WORRIED ABOUT DISRUPTING
MEMBRANES OR CAUSING MORE
PROBLEMS DOWNSTREAM BUT
OVERALL I THINK THOSE ARE
IMPORTANT TO LOOK AT,
PARTICULARLY FOR CORONA
VIRUSES.
>>THERE ARE THINGS YOU DO
WITH VACCINATION AND SPECIAL
CONSIDERATIONS YOU THINK ABOUT
IN TERMS OF MUCOSAL RESPONSES
DEPENDING ON THE TYPE OF
VACCINATION AND SOMETIMES
IMMUNE RESPONSE WON'T BE LOOK
AT AT ALL AND WILL FOCUSES ON
MUCOSAL.
>>THANK YOU VERY MUCH.
ONE QUESTION, HOW DO YOU THINK
ABOUT ADJUTANTS, IF THERE IS A
DIFFERENT TRIAL, HOW DO WE GET
TO EASE THESE ADJUTANTS?
>>THAT IS A VERY GOOD
QUESTION.
SO USUALLY WHEN IT IS INCLUDED
OR GIVEN TO THE PEDIATRIC
POPULATION, CLINICAL TRIALS
MANY TIMES ARE CONDUCTED IN AN
HD ESCALATION SO YOU GET
SAFETY DATA FIRST BEFORE YOU
THEN ROLL TO THE PEDIATRIC
SUBJECT AND YOU KNOW THAT IS
VERY SIMILAR WHEN YOU HAVE A
VACCINE POPULATION.
YOU HAVE TO CAREFULLY VALIDATE
THE SAFETY IN THE TEST GROUP
BEFORE YOU GIVE TO THE
PEDIATRIC SUBJECT BUT OVERALL,
THE PHYSICAL DEVELOPMENT, I
THINK -- AND MAYBE I AM
OVERSTATED BUT THIS WAS THE
APPROACH THAT WAS USED AND
THEN IF THERE WAS SOME ISSUE
WITH SAFETY THEN THE VACCINE
WOULD BE AN INVESTIGATIONAL
VACCINE, ADJUVANT
INVESTIGATION WILL BE TRIED
WITH THE SUBJECT AND THEN
CARRY ON FROM THERE BEFORE IT
IS GIVEN TO THE LARGER
POPULATION SO THERE IS NOT A
DIFFERENT CHUNK IN TERMS OF
THE OVERALL CLINICAL
DEVELOPMENT, JUST A MORE
CAREFUL DEESCALATING APPROACH
THAT IS GIVEN.
>>THANK YOU SO MUCH.
>>ONE MORE QUESTION OR CLOSE
FOR SESSION 3?
>>LET'S SEE IF WE CAN DO ONE
MORE QUESTION.
>>GO AHEAD.
>>THERE WAS ONE MORE QUESTION
THAT CAME UP IN THE CHAT A
COUPLE OF TIMES WHICH WAS
SHOWING A LOT OF TITER
NEUTRALIZING BUT NOT A LOT OF
TALK ABOUT DURABILITY AND THIS
IS TO THE GROUP, HOW YOU THINK
ABOUT DURABILITY IN YOUR
STUDIES AND IF YOU HAVE ANY
MAGIC BULLETS TO THE AUDIENCE?
>>I MEAN WE TYPICALLY LOOK AT
IT IN A SEPARATE STUDY SO
USUALLY THE FIRST STUDY IS TO
DETERMINE IF YOU ARE GETTING
THE TYPE OF ANTIBODIES YOU ARE
LOOKING FOR.
WHEN TALKING ABOUT DURABILITY,
IT DEPENDS WHO WE ARE LOOKING
FOR, IF WE ARE LOOKING FOR A
CERTAIN TYPE OF IMMUNE
RESPONSE TO COME UP BUT I
THINK WE DEFINITELY BEFORE WE
MOVE TO CLINICAL TRIAL WANT TO
KNOW WHAT THE DURABILITY LOOKS
LIKE AND UNDERSTAND WHAT IT
MIGHT BE IN A DIFFERENT POWER
POINT AND SOMETIMES IT MAY BE
LOOKED AT IN A SMALLER OUTCOME
WITH IT IS MORE DURABLE.
SOMETIMES IT INVOLVES THE
ADJUTANTS WHERE WE SEE A
HIGHER TITER AND SOMETIMES IT
TAKES LONGER FOR THE TITER TO
FALL BACK DOWN TO BASELINE BUT
IT IS SOMETHING WE WOULD DO IN
A DIFFERENT WAY AND STRUCTURE
HOW WE WOULD LOOK AT AND
ANSWER THOSE QUESTIONS.
>>OKAY, IF NO ONE ELSE HAS
ANYTHING TO ADD, THANK YOU ALL
SO MUCH.
THOSE WERE REALLY EXCELLENT
SESSIONS.
>>THANKS, EVERYONE
>>THANK YOU.
>>THANK YOU ANA AND CESAR FOR
MODERATING SECTION 2.
WE DON'T HAVE ENOUGH TIME FOR
FURTHER DISCUSSIONS AND IN THE
INTEREST OF TIME, WOULD LIKE
TO MOVE ON TO THE NEXT
SESSION.
>>THANK YOU, ANNIE.
WE WILL MOVE TON TO SESSION 3
WHERE WE WILL TALK ABOUT
ACCESS TO ADJUVANTS FOR
VACCINE DEVELOPERS.
THESE WILL BE VERY SHORT HIGH
LEVEL TALKS ON INDUCINGS A
VANITIES AND IF YOU HAVE ANY
QUESTIONS, PLEASE POP THEM IN
THE Q&A BOX.
AND WE DON'T HAVE A COMPONENT
OF DISCUSSION IN THIS SECTION.
IF YOU ARE CONCERNED ABOUT
THAT OR ANYTHING PRESENTED IN
THIS SESSION, I WOULD LIKE TO
POINT YOU TO THE FOLLOWING
RESOURCES THAT Dr. ALREADY
INTROACCUSED IN HER TALK.
THIS IS THE NIAID VACCINE
ADJUVANT COMPENDIUM WHICH
DISPLAYSA HAVEN'T CONSIDERING
A RIFT TICK AND META METADATA
AND FOSTERS COLLABORATIONS
BEYOND NIAID TO IDENTIFY
ADJUVANTS TAILOR TO SPECIFIC
VACCINE INDICATIONS.
AND I WOULD LIKE TO DISCUSS
ONE OF THE QUESTIONS THAT CAME
UP TODAY, WHAT IS THE BEST
ADJUVANT AND HOW DO I SELECT
AN ADJUVANT FOR A VACCINE.
AND AS OUR SPEAKERS SAID
TODAY, THERE IS NO PERFECT
ADJUVANT THAT IS SUITABLE FOR
ALL 16 TYPES AND JUST BECAUSE
IT IS GREAT IN ONE ANTIGEN
DOESN'T NECESSARILY MEAN IT IS
THE BEST FOR YOUR ANTIGEN SO
IN A PERFECT WORLD, THE
ANTIGEN WILL BE MATCHED BASED
ON THE ADJUVANT INDUCED IMMUNE
PROFILE AND THE CORRELATES OF
PROTECTION FOR MOST PATHOGENS.
HOWEVER IN A PERFECT WORLD, WE
DON'T HAVE ENOUGH INFORMATION
FOR EITHER ONE TO BE ABLE TO
COMBINE ANTIGENS IN OTHER
FORMULATIONS.
SO IN THE REAL WORLD, THE
ALTERNATIVE IS TO COMPARE AND
MULTIPLY WHICH IS DONE EARLY
IN THE PROCESS OF DEVELOPING A
VACCINE.
AND AS WE HAVE ALREADY SEEN IN
PREVIOUS TALKS, IT IS REALLY
IMPORTANT TO DO THIS EARLY ON
IN THE PROCESS OF DEVELOPING A
NOVEL VACCINE.
NIAID HAS SEVERAL PROGRAMS TO
PROMOTE ADJUVANT COMPARISONS
THROUGH SEVERAL PROGRAMS AND I
AM LISTING THEM HERE ALTHOUGH
I WILL NOT GO INTO THE
DETAILS.
IF YOU ARE INTERESTED IN
LEARNING MORE ABOUT THEM, I
WOULD DIRECT YOU TO THE URL
HERE AT THE BOTTOM OF THE
SCREEN.
AND WITH THAT, I WOULD LIKE TO
HAND THE STAGE OVER TO THE
FIRSTS PRESENTER, Dr. DAVID
BURKHART WHO WILL TALK ABOUT
THE ADJUTANTS.
>>THANK YOU, THANK YOU FOR
ALLOWING ME TO TALK ABOUT SOME
OF THE ADJUTANT WORK I AM
DOING AT UNIVERSITY OF MONTANA
AND WITH INIMMUNE AS A
PARTNER.
NEXT SLIDE, PLEASE.
THE ADJUTANTS I WILL SHOW YOU
TODAY ARE REALLY THE PRODUCT
OF A UNIQUE PUBLIC-PRIVATE
PARTNERSHIP BETWEEN THE CENTER
AND UNIVERSITY OF MONTANA WITH
THE COMPANY INIMMUNE.
BOTH WERE FOUNDED IN 2016 AND
HAVE GROWN FROM 15 TO 80
EMPLOYEES WORKING AS ONE BIG
TEAM.
OUR STRENGTHS ARE PRECLINICAL
CHEMISTRY, FORM OPERATION AND
IMMUNOLOGY GROUPS AND WORK ON
DISCOVERY RESEARCH, IP
GENERATION AND PROCESS
DEVELOPMENT EXPERTSE AND THIS
HAS GROWN INTO A STRONG AND
GROWING PIPELINE OF NEW
CANDIDATE DRUGS AND VACCINES
THAT ARE NOW MOVING THROUGH
IND AND PHASE 1 TRIALS AND
ALSO IN NO SPAL PART THIS IS
DUE TO AN INDUSTRY OF AM DEM
MICK AND INDUSTRY PARTNERS WE
HAVE IN THIS SPACE.
AND ALL OF OUR PROGRAMS
FOCUSES ON LATE STAGE
SYNTHETIC ADJUVANTS, THIS HAS
RESULTED IN THE LIGANDS.
THE THREE LISTED HERE, THE
TLR4 THAT HAVE SUPERIOR
THERMOSTABILITY, STRONG SAFETY
AND EFFICACY PROFILE ACROSS
MULTIPLE ANTIGENS AND ANIMAL
MODELS.
THEY ARE EXTREMELY FORMULATED
IN DIFFERENT CHARACTERISTICS,
CAN BE INCORPORATED IN
LIPOSOMES, EMULSANTS OR ALUM
AND CAN GREATLY PRODUCE THE
IMMUNE RESPONSE OF THE
ADJUVANT ITSELF.
THEN WE HAVE THE TLR7/8,
REALLY STRONG PRODUCING
ADJUVANTS AND AGAIN CAN BE
FORMULATED AND DELIVERED IN A
VARIETY OF DIFFERENT WAYS,
BOTH INTRAMUSCULAR AND
INTEREST THAT NAVAL DELIVERING
A STRONG TH1 AND CMI RESPONSE.
AND THEN PROBABLY OUR MOST
UNIQUE PR AGO FIFTH
REPRESENTED BY OUR MEANINGFUL
AGO FIFTH AND THE UM-1098 IS A
NOVEL MINCLE AGO FIFTH THAT
PRODUCES A STRONG TH17 IMMUNE
PROFILE WHICH CAN BE IMPORTANT
IN FUNGAL PATHOGENS SUCH AS TB
AND EASILY FORM FORMULATED IN
LIPOSOME 'EM MULLS OR NAN MOW
PARTICLES AS WELL.
IN LATE STAGE, WE HAVE A
NUMBER OF SYSTEMS THAT Dr.
MILLER PRESENTED ON JUST A
LITTLE BIT AGO WHICH IS A
NOVEL COMBINATION OF OUR TLR4
AND INI2002 AND CAN INUSE IT A
REALLY NICE BALANCE OF
ANTIBODY AND IMMUNE RESPONSE.
AND THEN WE HAVE A NOVEL STING
AGO FIFTH, THOSE WERE A LITTLE
EARLIER BUT WE HAVE A FEW LEAD
MOLECULES ADVANCING AND THEN
EARLIER STILL, AN IL-1 BETA AT
THE UNIVERSITY OF MONTANA TO
DISCOVER NOVEL SYNTHETIC
COMPOUNDS WITH ADJUVANT
ACTIVITY.
SO THIS SLIDE KIND OF
SUMMARIZES WHAT I JUST TOLD
YOU, THE DIFFERENT PAR THESE
ARE AGONIZING, IN 2002 AND
2004, THIS IS A COMBINATION OF
INI2002 WITH TLR4 AND THEN THE
SECOND SYSTEM, THE 2004
COMBINED WITH A COMPONENT, THE
4001 WITH TLR7/8 AND THEN THE
COMBINATION OF TRAC-478 AND
TLR4 WITH SAPONIN AND LEADING
TO THE MINCLE AND THAT INDUCES
THE ROUTES OF DELIVERY TO BE
USED UNIVERSALLY INTRANAVAL,
INTRAMUSCULAR AND THEN THE
DIFFERENT TOXICITY STAGES
THESE ARE AT.
I SHOULD POINT OUT THE 2004
HAS JUST STARTED A PHASE 1
CLINICAL TRIAL FOR ALLERGY IN
A NASAL IN STKPRAEULZ THAT IS
THE SAME DOSE WE WOULD USE AS
A VACCINE AGO FIFTH
INTRANASAL.
AND THEN YOU CAN SEE AT THE
BOTTOM THE QR CODE TO THE
VACCINE COMPENDIUM SO IF YOU
NEED MORE INFORMATION, YOU CAN
ACCESS IT THERE.
THANK YOU AND I WOULD BE HAPPY
TO ANSWER ANY QUESTIONS LATER.
>> THANK YOU VERY MUCH.
THE NEXT PRESENTATIONS
PRESENTATION WILL BE NIKOLAI
PETROVSKI ON ADJUVANTS.
>>THANK YOU, IF I COULD HAVE
THE SLIDES PLEASE IN NEXT
SLIDE.
SO YEAH IF WE -- SORRY, BACK
ONE.
BACK ONE SLIDE.
>>I THINK IT IS JUST DELAYED.
>>OH, I SEE, SORRY.
SO YEAH, YOU COULD GO TO THE
NEXT SLIDE.
SO WE STARTED THIS PROGRAM AT
NIH ALMOST 20 YEARS AGO WITH
OUR ADJUTANT DELTA INULIN,
CRYSTAL LIESS INTO STRUCTURES
AND DEVELOPS A UNIQUE INULIN
PROPERTY PARTICULARLY IF IT IS
FORMULATED WITH AN ANTIGEN AND
HENCE THE ANTIBODY RESPONSE
AND THE UNIQUE PROPERTIES WAS
IT HAD ANTIGEN PROPERTIES AND
FOR INSTANCE DIDN'T ACTIVATE
ANY ISSUES AND THE LONG AND
THE SHORT OF IT WAS EFFICACY
AND CONDUCTING A SWELLING IN
THE FOOT PAD AND A GOOD
ADJUTANT MAKES A HAPPY AND
HEALTHY BABY AND WHAT WE WERE
ABLE TO SEE IN LOOKING AT THE
SURVIVAL OF MOUSE PUPS AT ONE
DAY OF AGE, INJECTED WITH
ININFLUENZA VACCINE AND A LOT
OF PEOPLE ARE AWARE THEY WORK
IN ADULTS BUT NOT IN NEWBORNS
SO THE PUPS WOULD DIE AND SO
WE INCLUDED THE INULIN WHICH
RESULTED IN A COMPLETE
SURVIVAL.
SO WE WERE ABLE TO SHOW THIS
IS EXTREMELY DURABLE AND THE
SINGLE DOSE IN THE MOUSE PUPS
SURVIVING THESE WITH THE
FORMULATED INULINA VANITY AND
LOOK AT THEM SIX MONTHS LATER
AND COULD ANALYZE THE
PROJECTION.
NEXT SLIDE.
BUT LIKE EVERYONE, WE DIDN'T
REST ON OUR LAURELS WITH AND
USING AI TO IDENTIFY THE
AGOIFTS.
WHAT WE FOUND, THERE ARE MANY
DIFFERENT CLR AGOIFTS AS WELL
AS OTHERS AND ABLE TO PROVIDE
A BENEFIT AND AS A CONSTANT A
COUPLE OF YEARS AGO WE HAD A
ADJUTANT DISCOVERY CONTRACT
WHERE WE WERE USING ARTIFICIAL
INTELLIGENCE TO IDENTIFY HUMOR
ANIMAL AGOIFTS AND SO WE
ARRIVED AT THE CYS VA C2, THEN
CPG AND CPG AND WITH THIS
FUSION WE WERE ABLE TO PROTECT
MICE AGAINST AN AREA SO WILL
MICRO BACTERIAL TB CHALLENGE
REDUCING LUNG INFECTION ALONG
THE SAME ORDER YOU MIGHT SEE
WITH VPT VACCINE.
AND AGAIN, I WON'T GO INTO
THIS MORE AS IT WAS
EXPENSIVELY PUBLISHED BUT
SUFFICE TO SAY THAT AN
INTRAMUSCULAR VACCINATION MORE
RECENTLY HAS BEEN FOUND TO
CARRY THE LOAD FOR THE
VACCINE.
NEXT SLIDE.
SO FOR YEARS YOU WORK EASILY
TO PUT THIS INFORMATION IN A
FREE SLIDE BUT SUFFICE TO SAY
THERE IS QUITE A DISEASE MODEL
LIST USED IN ADVAX ADJUVANT
TESTING.
NEXT SLIDE.
AS I MENTIONED BEFORE, ONE OF
THE DUTIES OF THIS PLATFORM
APART FROM ITS EFFICACY IS IT
IS VERY GOOD AT DIAGNOSING
HUMAN EFFICACY SO WHAT YOU SEE
HERE, I FOCUSSED ON A VAXINE
WHICH IS NOW APPROVED TO BE
USED IN THE MIDDLE EAST AND BY
ADDING THE GPG ADJUVANT, IT
SPIKED THE NUMBER OF T CELLS
BUT EVEN WITH CPG, YOU CAN SEE
THE T CELLS ACTIVATED AND WITH
THE PROTEIN, IT INCREASES THE
T CELLS BUT ALSO CTL ACTIVITY.
SO IF YOU LOOK AT CYTOTOXIC
KILLING, YOU CAN SEE THE
ACTIVATED T CELLS.
[INDISCERNIBLE]
NEXT SLIDE.
SO AS I MENTIONED THERE WERE
MORE THAN A HUNDRED CASES ON
THESE DIFFERENT STUDIES DONE
WITH THE ADJUVANTS.
I AM HAPPY TO SHARE ANY OF
THESE.
MOSTLY ARE FREELY AVAILABLE
AND THIS IS LISTED ON THE
DATABASE SO JUST GIVE ME A
TOUCH AND I WILL BE HAPPY TO
FORWARD THEM TO YOU.
NEXT SLIDE.
SO THIS TO WRAP UP, I THINK
THE ADVANTAGE OF THE PLATFORM,
IT IS EASY TO MANUFACTURE.
YOU KNOW, WE CAN DO THIS WITH
CPG55 WITH OVER 5000 VACCINES,
IT HAS LOW REACTIVITY, IMMUNEO
GENUINE NICK, WE GET SUPERIOR
YOUR TRANSLATION FROM MICE TO
HUMANS AND WITH THE TLR
ADJUVANTS IN THE PIPELINE.
AND IS ABLE TO BE DISABLED
ALMOST INDEFINITELY AND WE
KNOW THE FORMULATION IS EASY
TO STORE AT ROOM TEMPERATURE.
AND THE CPG55.2 WE BELIEVE IS
THE MOST POTENT AGO FIFTH
AVAILABLE AND TEN TIMES MORE
POTENT THAN CPG18 OR TLR9.
THAT CAN BE FORMULATED BUT
FORMULATED INDIVIDUALLY WITH
ALUM, TO MAKE A ALUM-CPG
FORMULATION WHICH WE ARE NOW
TESTING AND SUFFICE TO SAY WE
CONTINUE TO DEVELOP OTHER CL T
L.A. ADJUVANTS WITH ADDITIONAL
ADJUVANTS IN THE PIPELINE AND
AGAIN, VERY HAPPY TO PROVIDE
THESE AS PART OF THE
COLLABORATION.
THANK YOU VERY MUCH.
>>THANK YOU VERY MUCH FOR
THAT PRESENTATION.
I AM LOOKING ON TO DOCTOR SUM
IL DAVID.
>>THANK YOU DAVID, SO THE
TALK TODAY WILL BE ON THE
ALHYDROXIQUIM-II AND AS SHOWN
IN RED IS A POTENT MOLECULE.
THIS IS BLENDED WITH ALUMINUM
HYDROXI AND SPECIFICALLY
ALLOWS BINDING ON THE SURFACE
TO LIGAND EXCHANGE OR
CHEMISORBTION WHERE IT
EXCHANGES ON THE LOOM HIM IN
HYDROXIDE SURFACE.
THE CONSEQUENCE OF THIS IS
SHOWN IN THE NEXT SLIDE AND
THIS ALLOWS FOR A VERY
SPECIFIC AND SUBSTANTIAL ALUM
CRUCIAL ON PRECISION INJECTING
THE SMALL MOLECULE INTO THE
CELL AND EVEN MORE
IMPORTANTLY, IT IS BECAUSE OF
THE ALUM THAT IT PROVIDES THE
DRAINING LYMPH NODE WHERE IT
IS NEEDED TO CONJUNCTION WITH
THE ADJUTANT WHICH WILL ALSO
RISE UP TO THE LYMPH NODE.
AND THE STRUCTURE I SHOWED YOU
IN THE PREVIOUS SLIDE BECAUSE
THE ALUM, IT IS STABLE AND THE
ADJUTANT CAN BE AUTOCLATED
WITH THE SMALL MOLECULE AGAIN
SHOWING THE STABILITY OF THE
SMALL MOLECULE.
NEXT SLIDE, PLEASE.
SHOWN ON THE RIGHT IS THE NEW
ANTIBODY IN HORSES COMPARING
THE T CELL IMMUNITY TO LIVE
TITERS.
ON THE LEFT IS SHOWN A PRETTY
PRONOUNCED REACTION FROM T
CELL THAT HAS BEEN SHOWN IN
MICE AND PUBLISHED, ADJUVANTED
WITH THE ALUM OR WITH
ALHYDROXIQUIM-II AND AS
EXPECTED FOR A USEFUL STUDY
LIKE THIS, THIS IS STRONG
SHOWING FOR AN IMMUNE
RESPONSE.
NEXT SLIDE, PLEASE SO THAT IS
SHOWING THE EFFICACY OF THE
STUDY, THANK YOU VERY MUCH.
>>NEXT WE HAVE GABRIEL.
>>THANK YOU VERY MUCH, I WILL
JUST CONTINUE HERE WITH THE
CAF ADJUVANT FORM LAKES WITH
CATIONIC, MIXED WITH DDA AND
THEN WE HAVE A MINCLE AGO
FIFTH WHICH IS A TD B OR MMG
WHICH FUNCTIONS TO STABLE ICE
LIPOSOMES AND SO IT COULD BE
USED LATER.
THIS GIVES A STABLE AND WELL
CHARACTERIZED LIPOSOME WITH
MORE THAN THREE YEARS'
SHELF-LIFE AT 2-8 DEGREES.
IT IS UPSCALABLE WITH GM P FOR
THE MANUFACTURING PROCESS.
NEXT SLIDE, PLEASE.
SO WE HAVE IN CLINICAL TRIALS,
WE HAVE THREE DIFFERENT ADJUVA.
ONE IS CAF01 WHICH IS USED IN
FIVE FINALIZED AND ONE ONGOING
PHASE 1 TRIALS.
IT HAS FOUR DIFFERENT ANTIGENS
AND THE PROFILE IS VERY STRONG
WITH TH1, TH17 AS WELL AS
ANTIBODY RESPONSES SO WE HAVE
SEEN THESE IN THESE STUDIES.
THEN WE HAVE THE NEXT ONE
WHICH IS CAF09B USED IN TWO
FINALIZED PHASE 1, USED IN A
COUPLE OF TRIALS WITH CANCER
WITH TAA AND NEOEPITOPES AND A
STRONG CTL INDUCTION IN THE
TWO FINALIZED PHASE 1 TRIALS.
AND THE NEWEST CAF ADJUVANT WE
HAVE IS THE 10B WHICH
INCORPORATESTLR9 AGO FIFTH AND
WE HAVE ONE SCHEDULED PHASE 1
CLINICAL TRIAL.
WA WE HAVE SEEN WITH CAF10B IS
INCREASED TH1 AND TH17 AND
ANTIBODY RESPONSES IN NONHUMAN
PRIMATES.
NEXT SLIDE, PLEASE.
SO THE CAF ADJUVANTS HAVE BEEN
FOUND TO BE SAFE IN SEVERAL
STUDIES, FINALIZED AND ONGOING
PHASE 1 TRIALS.
ALSO WE HAVE ESTABLISHED MOA
AND SIMPLE MIXING OF ANTIGEN
FOR ADJUVANT.
IT IS SIMPLE TO USE WITH THE
MIXING OF ANTIGEN WITH
ADJUVANT AND HAVE SEEN THIS
WITH PROTEINS, PEPTIDES,
INACTIVATED VIRA AND SPLIT
VIRUS AND MRNA AND THEY ARE
AVAILABLE FOR COLLABORATION
FOR NONGM P MATERIAL IS IT L
AND COLLABORATION WITH CRODA
FOR LARGE SCALE PRODUCTION.
>>THANK YOU VERY MUCH, SORRY
FOR THE TECHS TECHNICAL ISSUES
WERE BEFORE, HOPE MY AUDIO IS
BACK NOW.
THE NEXT TALK WE HAVE MANGALA
RA RAO.
>>GOOD MORNING, CAN YOU HEAR
ME?
>>YES, WE CAN.
>> SO TODAY I WILL TALK ABOUT
ARMY LIP TOMORROW FORMULATION
ADJUVANT.
OVER THE YEARS THEY HAVE BEEN
COMBINED AND ONE OF THEM IS U
AND THESE CONSIST OF LIPIDS
WITH ALF Q&A LFQA AND AS YOU
CAN SEE CAN BE MIXED TO ANY
STRENGTH YOU WANT.
THEY CAN BE USED WITH AFLQ OR
EXHAUST TO GENERATE ALFQ2 AND
ADDING IN THE LIPIDS.
SO WHAT IS THE DIFFERENCE?
THE MAJOR DIFFERENCES ARE IN
THE PHOSPHALLPID AND IN THE
AFL Q&A FLQA.
THE APPEARANCE OF AFLB IS BIG
AND YOU DO NOT GET MANY
PELLETS.
ALSO THE SIZE IS DIFFERENT,
WHERE YOU HAVE THE 51UM AND
PHOSPHOLLIPID RANGING FROM
30 MILLIMETERS TO ONE MICRON.
NEXT SLIDE.
SO ON THE NEXT SLIDE WE HAVE
THE STUDY OF THE -- THE SAMPLE
OF PRECLINICAL AND CLINICAL
STUDIES, YOU HAVE MALARIA IN
MICE, THE CAMPY CONJUGATE AND
ON THE RIGHT SIDE, THE HIV-1
ENVELOPE PROTEIN WITH GP120
SPECIFIC BONE MARROW PLASMA
CELLS.
AT THE BOTTOM, YOU SEE SARS
COV2 PHASE 1 STUDY WHICH WAS
FORMULATED SHOWING HIGH
NEUTRALIZING ANTIBODIES IN ALL
VACCINES.
THIS PORTION SOMEHOW IT NOT
COME OUT WELL BUT THAT IS
OKAY.
NEXT SLIDE, PLEASE.
THIS SHOWS THE PHASE 3
COMPLETED STUDIES WITH FOUR
TRIALS AND THERE ARE SEVERAL
MORE IN THE PIPELINE INCLUDING
TESTING OF SENSITIVE PEPTIDES
FOR INFLUENZA 2.
SO IN THIS CASE, YOU SEE THE
NUMBER OF DOSES ADMINISTERED
TODAY AND THE NUMBER OF PEOPLE
WHO HAVE BEEN ADMINISTERED AS
Q AND DOWN BELOW YOU SEE THE
ARTICLE 60 WHICH WAS MENTIONED
ABOUT THE PHASE 1 CLINICAL
TRIAL AND THE NUMBER OF PEOPLE
VACCINATED WHO RECEIVED THAT
ADJUVANT.
SO BASED ON THIS AS WELL AS
ONGOING STUDIES, THE
FORMULATIONS AFLQ WERE SAFE
AND THERE WERE NO PREVIOUS
EVENTS TO DATE.
THE ALF CAN BE READILY
COMBINED FOR MARKETABLE
EXISTING AND EMERGING LYNN
NEXTIOUS DISEASES.
THE ABILITY TO INCORPORATE
ALFQ ADJUVANTS IN EARLY
CLINICAL TRIALS, SUCCESSFULLY
MANUFACTURED AT 7.5 LITTERS OF
ALF55, CURRENTLY STABLE FOR
6.5 YEARS ON SAABABILITY
PROGRAM AND WILL SHOW 7.5 IN
OCTOBER.
THE ALFQ HAS BEEN USED IN
THREE RABBIT
PHARMACOLOGY-TOXICOLOGY
STUDIES WITH GOOD SAFETY
PROFILE AND NO ADVERSE
REACTIONS.
AND I WOULD LIKE TO THANK THE
LEADERSHIP, THE NUMEROUS
INTERNAL AND EXTERNAL
COLLABORATORS AND CLINICAL
TRIALISTS WHO WERE ALL
RESPONSIBLE FOR THIS
FORMULATION.
WE COULDN'T HAVE DONE IT
WITHOUT YOU AND ESPECIALLY
WITH THE CLINICAL TRIAL
PARTICIPANTS.
SO THANK YOU VERY MUCH.
NEXT SLIDE, IF YOU HAVE ANY
QUESTIONS, PLEASE SEND THEM IN
THE CHAT BOX.
THANK YOU.
>>THANK YOU.
MOVING ON TO THE NEXT
PRESENTATION BY Dr. CHAD
COSTLEY FROM BLUE WILLOW
BIOLOGICS.
>>THANK YOU, GOOD MORNING
ALL.
I WILL TALK ON THE INTRANASAL
VACCINE ADJUVANT PLATFORM,
MOVE ON.
SO I HAVE KEPT THIS SHORT AND
LEAVING OUT ANY DATA WOULD BE
DOING A DISSERVICE TO IT.
SO WE WILL TALK ABOUT THE
ANIMATION OF A NOVEL
INTRANASAL ADJUVANT PLATFORM.
IT IS DIFFERENTIATED BY THREE
THINGS, I WOULD ARGUE, THE
NATURE OF IMMUNE RESPONSE, THE
HUMAN SAFETY AND TOXICOLOGY,
SOME ARE PRICED WE ARE AS FAR
ALONG AS WE ARE, AND PLATFORM
FLEXIBILITY.
THE NATURE OF THE IMMUNE
RESPONSE, WE GET THE MUCOSAL
SYSTEMIC AND CELL-MEDIATED
IMMUNITY, THERE IS DECREASED
VIRAL CARRIAGE AND SHEDDING,
BIASED TH1 OVER TH2 AND B AND
T CELL HOMING TO MUCOSA FOR
LONG-TERM MEMORY.
WE HAVE BEEN IN A CLINICAL
TRIAL AND NEVER SEEN ANY
SERIOUS ADVERSE EVENT,
SPECIFICALLY ANY TOXIC
REACTION AND WE HAVE HAD
EXTENSIVE WORK FOR THAT.
NEXT SLIDE, PLEASE.
IT IS NEEDLE-FREE, LOW COST,
THERMOSTABLE, ESTABLISHED CMC
AND GM P, WELL ESTABLISHED AND
WELL CHARACTERIZED.
SO A LOT HAS BEEN ACCOMPLISHED
BY A SMALL COMPANY.
MECHANISM OF ACTION, I WILL
NOT SPEND MUCH TIME ON THIS
BUT HIGHLIGHT A FEW POINTS.
THE AND GENUINE IN DENDRITIC
CELLS, THE SAMPLING, YOU GET
UPREGULATION OF TLR2 AND TLR4,
SUPPRESSION OF TH2 SITES
CANES, ILC2 AND ALARMIN
PRODUCTION.
YOU GET ACTIVATION OF TH1
CELLS AND SITES KIND AND SEE
THE PRODUCTION OF SIG AN AND
TH17.
NEXT SLIDE, PLEASE.
THE PURPOSE OF THIS SLIDE IS
TO OVERWHELM YOU WITH TECH
BOXES WHICH I WILL NOT TALK
ABOUT IN THIS FORMAT BUT THE
POINT HERE IS THE EXTENT OF
THE WORK DONE.
ON THE LEFT YOU HAVE THE
PATHOGEN AND THE TYPES.
WE HAVE DONE HERPES PROGRAM,
FULL VIRUS VACCINE, SO THE
PLATFORM CAN INCORPORATE A
LARGE VARIETY OF ANTIGEN
TYPES.
PROOF OF CONCEPT HAS BEEN
ESTABLISHED IN SMALL AND LARGE
ANIMALS INCLUDING NONHUMAN
PRIMATES ACCORDING TO THE
CLINICAL WORK WE HAVE DONE AND
CHALLENGE SHEDDING AND ALL OF
THOSE THINGS LOOKED AT IN THE
SAFETY PROFILE.
WE CAN GO FORWARD.
THE LAST SLIDE I WILL LET
STAND ON ITS OWN AND WILL GO A
LITTLE OFFSCRIPT.
NOTHING I WILL SAY IS
DIFFERENT ON THIS SLIDE BUT I
WANT TO SPEAK TO SOME OF THE
EARLY CONVERSATIONS WE HAD
THIS MORNING.
THERE WAS TALK ABOUT THE
CHALLENGES PROVIDING SAFETY
AND GM P WITH ADJUVANTS AND
THAT IS CERTAINLY TRUE FOR
INTRANASAL AS WELL.
WE HAVE HAD THREE SUCCESSFUL
TOX STUDIES.
CMC IS WELL CHARACTERIZED.
WE HAVE DONE ALL OF THIS WITH
FEWER THAN 15 EMPLOYEES
BECAUSE OF THE GREAT SUPPORT
WE HAVE WITH THE GATES
FOUNDATION, NIAID AND A GROUP
OF PRIVATE INVESTORS WHO ARE
VERY COMMITTED TO GLOBAL
HEALTH.
IT IS SOMEWHAT OF A UNIQUE
STORY.
THE EFFICACY FROM PHASE 1 WE
HAVE SEEN IN CLINICAL TRIALS
ARE ENCOURAGING WHICH IS THE
FIRST FOCUS OF A INTRANASAL
ADJUVANT.
IT IS OPTIMIZED WITH DELIVERY
AS TALKED ABOUT IN OTHER TALKS
TODAY AND WE'RE AT THE PLACE
AS A COMPANY WHERE THIS
TECHNOLOGY DESERVES THE
SUPPORT OF THOSE WITH MORE
RESOURCES THAN A SMALL COMPANY
CAN GENERATE ON OUR OWN AND WE
LOOK FORWARD TO --
>>WE JUST LOST YOUR AUDIO.
>>YOU HAVE ME NOW?
>>WE CAN HEAR YOU WELL.
>>I AM BASICALLY DONE.
I DON'T KNOW WHAT HAPPENED AT
YOUR END, SOUNDS LIKE OTHERS
HEARD ME SO APPRECIATE YOUR
TIME TODAY AND THANKS FOR
THAT.
>>WOLFGANG, CAN YOU HEAR US?
>>I THINK WOLFGANG IS
HAVING --
>>I LOST MY AUDIO --
>>WE CAN HEAR YOU.
>>OKAY, GOOD.
THANK YOU SO MUCH.
SO YOU WERE DONE WITH THE
PRESENTATION?
>>YES, I WAS, WE'RE FINE.
>>THANK YOU, THANK YOU SO
MUCH, LET'S MOVE ON NEXT TO
ELIZABETH NORTON FROM TULANE
UNIVERSITY.
>>THANK YOU VERY MUCH, THANK
YOU TO WOLFGANG AND OTHERS WHO
INVITED ME FOR THIS TALK, CAN
EVERYONE HEAR ME OKAY?
>> YES, WE CAN.
>>SO I WILL TALK ABOUT DMLT
AND LTA1 ADJUVANTS.
NEXT SLIDE.
SO THIS WORK WE HAVE DONE WITH
THE ADJUVANTS AND GIVE A NOD
TO MY MENTOR AND THE POINT OF
THESE ARE THE ADJUVANT
SELECTION THAT ALLOWS THE
DELIVERY OUT TO BE A PARTNER
IN VACCINATION AND ALSO ALLOWS
A LOT OF VARIATIONS IN INFANT
FORMULA SO PILLS, ORAL, NASAL,
INTRAMUSCULAR, INTRADERMAL AND
TRANSCUTANEOUS WITH
CONSIDERATIONS OF TISSUE
SPECIFIC INTERACTIONS.
AND THEN YOU CAN SEE THE
ANTIGEN FORM.
NEXT SLIDE.
SO WE HAVE THENTEROTOXIN BASED
ADJUVANTS DERIVED FROM HEAT
LABILE TOXIN OF E COLE LIE.
THIS HAS BEEN AROUND FOR ABOUT
20 YEARS, CAN BE DELIVERED BY
ORAL, SUBLINGUAL, INTRADERMAL,
INTRAMUSCULAR AND
TRANSCUTANEOUS.
IT HAS BEEN IN CLINICAL
TRIALS.
IT HAS BEEN IN TEN STUDIES,
MANY OF THESE PUBLISHED SO
PHASE 1 AND PHASE 2, ETEC,
POLIO, HIV AND SHIGELAA.
THERE HAS BEEN NO SAE IN
EITHER INFANTS OR ADULTS.
AND THEN THE NEW ADJUVANT,
LTA1, THIS IS AN A1 DOMAIN OF
LT AND THIS CAN BE USED
INTRANASAL, INTRAPULMONARY OR
INTRADERMAL OR INTRAMUSCULAR.
THERE HAS BEEN NO CLINICAL
TRIAL YET BUT WE HAVE PHASE 1
PLANNED FOR 2026 AND THE BASIC
WAY THESE WORK IS TO DELIVER
TO MUCOSAL TISSUE TO PROMOTE
LOCAL AND SYSTEMIC IMMUNITY,
THEY CAN BE DELIVERED BY
INJECTION TO PROMOTE SYSTEMIC
IMMUNITY AND MAY ALSO DIRECT
IMMUNITY TO MUCOS AL TISSUE.
I SAY MAY BECAUSE IT HAS A
STRONG RESPONSE TO THE
INDIVIDUAL YOU ARE TRYING TO
DIRECT IMMUNE ACTIVITY.
SO WE COMBINE IT WITH AN
ANTIGEN AND IT GIVES YOU A
TH1, TH2 AND TH17 OR IGG/IGA
MULTIFACETED RESPONSE.
IT HAS GOOD VIAL STABILITY,
THERE IS EASY MANUFACTURING
THROUGH E. COLI EXPRESSION
SYSTEMS FOR LARGE COUNTIES AND
THERE IS A LOT AVAILABLE AND I
WOULD LIKE TO SAY ONE OF THE
KEY PARTNERS FOR
MULTIDEVELOPMENT HAS BEEN
PASSED AND THEY ARE OPENING A
CLINICAL TRIAL SUPPORT
INCLUDING GM LT.
AND NEXT SLIDE.
RECENT CLINICAL TRIALS FOR
DMLT AND IT REDUCED SHEDDING,
INCREASED PLASMA MA ANTIBODY
RESPONSES AND INCREASED
PROTECTIVE EFFICACY FROM
23 PERCENT FROM THE ANTIGEN
ALONE TO 65 130EU7B 9 PERCENT
AND WITH THE OTHER STUDIES,
THE TYPE OF IMMUNE RESPONSE
WAS DIFFERENT IF YOU LOOK AT
THE DIFFERENT AGE GROUPS
BECAUSE WITH THE ETEC VACCINE
IN INFANTS VERSUS ADULTS.
IF YOU ARE REALLY TARGETING
INFANTS, I THINK TRYING TO
OBSERVE BOTH THE PROTEIN AND
HOLLY SACK RESIDE RESPONSES
CAN BE DIFFERENT AND GOING TO
THE NEXT SLIDE, WITH LTA1, WE
HAVE A PLANNED CLINICAL TRIAL.
NEXT SLIDE, PLEASE.
AND THIS IS FOR THE VACCINE
AGAINST PNEUMONIA, WE TESTED
LTA1 AND THE GREEN BAR IS
REDUCING THE BACTERIAL BURDEN
AND THIS IS COMPARED SHOWN IN
THE PURPLE BAR, THE PH
CONSUMER RESPONSE RELATING TO
THE T CELL RESPONSE AND WHEN
YOU LOOK AT THE T KRELS, WHAT
WE'RE REALLY EXCITED ABOUT IS
THIS WILL BE VERY INTERACTIVE
WITH OTHER DISEASES SUCH AS
PULMONARY DISEASE.
SO WE ARE CONTINUING TO
EXPLORE THIS WITH NIH SUPPORT
IN THE UPCOMING CLINICAL TRIAL
AND ALSO LOOKING FOR PARTNERS
IN SUPPORT.
AND IF YOU ARE INTERESTED IN
THIS, YOU CAN GO TO THE
DATABASE FOR ADDITIONAL
STUDIES OR CONTACT ME.
THANK YOU.
>>THANK YOU VERY MUCH FOR
THAT, MOVING ON TO THE NEXT
PRESENTATION BY Dr. ROBERT
ERNST FROM THE UNIVERSITY OF
MARYLAND.
>>I WOULD ALSO LIKE TO THANK
THE ORGANIZERS FOR GIVING US
THE OPPORTUNITY TO BE ABLE TO
TALK ABOUT THE FAMILY OF
ADJUTANTS AND THANK THEM FOR
OUR FUNDING OVER THE LAST
NUMBER OF YEARS TO GET US
WHERE WE ARE.
NEXT SLIDE, PLEASE.
SO THE BEST TECHNOLOGY IS A
NOVEL WAY OF MAKING TLR4
AGOIFTS AND IT IS CALLED
BACTERIAL ENZYME AUTOMATIC
CHEMISTRY AND IT STARTED AS A
PROCESS THAT ALLOWS YOU HAD TO
MAKE TLR4 IN AS SHORT AS 10 TO
14 DAYS.
OVER THE TIME WE HAVE SWITCHED
FROM BIOLOGICAL ON THE LEFT
SIDE OF THE SCREEN TO THE
RIGHT SIDE WHICH IS SYNTHETIC
AND WE HAVE TWO MOLECULES
CURRENTLY AVAILABLE FOR
VACCINE DEVELOPMENT, 438S AND
470S.
WE HAVE HAD THE PLEASURE OF
WORKING WITH A LOT OF PARTNERS
BOTH WITH GOVERNMENT AND
PRIVATE INDUSTRY AND ONE OF
THE THINGS WE WANT TO PROVE
EARLY ON IS SHOW BREADTH OF
RESPONSE AND WE WILL GET INTO
THAT IN A LITTLE BIT.
THE IDEA HERE IS WE HAVE HAD
THE ABILITY TO HAVE ONE
MOLECULE TO BE USED IN A LOT
OF DIFFERENT ANTIGENS AND
FORMULATED IN A LOT OF
DIFFERENT WAYS AND ON THE
RIGHTHAND SIDE, OUR CURRENT
MOLECULES.
SO NEXT SLIDE, PLEASE.
WE HAVE MADE A LOT OF ADVANCE
OVER THE LAST FOUR OR FIVE
YEARS IN THIS AREA AND ONE OF
THE THINGS WE CAN DO IS WE
GENERATE A ROBUST IMMUNE
RESPONSE FOR PRETTY MUCH ANY
ANTIGEN IN ANY MODEL WE HAVE
LOOKED AT SO FAR SO WHEN I SAY
ROBUST IMMUNE RESPONSE, WE GET
A BALANCED TH1 OR TH2 RESPONSE
ALL THE TIME.
WE ALSO GET INCREASED IGG2B
AND IGG3TITERS.
WE ALSO GET INCREASEDT CELL
RESPONSES.
WE ALSO GET MEMORY AND AGE
RESPONSES AND THIS WAS AFTER
THE ANIMALS WERE PRIME
HOUSTONED.
WE GET INCREASED B-CELL MEMORY
AND EFFICACY IN AGING ANIMALS
FOR INFLUENZA AND AERUGINOSA
IN MICE OF 18 MONTHS.
SO OUR BACTERIAL MODELS, WE
HAVE DONE RSV, P HPV, SARS 2,
RBD AND SOME OF THESE ARE IN
PROCESS AND SOME ARE ONGOING
BUT I WOULD LIKE TO POINT OUT
TWO WE HAVEN'T PUBLISHED YET,
FROM JULIE.
[INDISCERNIBLE]
AND WHAT WE ARE LOOKING AT IS
THE LESIONS, THESE ANIMALS
COMPLETELY HEAL THEIR SKIN
INFECTIONS THAT ARE PENDING.
THE BOTTOM ONE, INFLUENZA
CHALLENGE MODEL, THIS IS ONE I
HAVE DONE MYSELF AND WITH
UNIVERSITY OF BALTIMORE, SO
THIS IS THE LGG1 WITH ANTIGEN,
THIS IS A 2-WEEK PRIME BOOST
AND AS YOU CAN SEE IN THE
GREEN AND BLUE BAR, BLUE
CIRCLES, WE GET STRONG IGG1
AND STRONG IGG2A.
NEGOTIATION SLIDE, PLEASE.
WHERE WE ARE NOW IS WE CAN GET
ANTIGEN DOSE OF HA FOR
QUADRAVALENT AND CROSS
PROTECTION BETWEEN THE STRAINS
IN RISE MICE, RABBITS, DOGS
AND BAB BOONES AND WE CAN DO A
MIXED DELIVERY OF INTRANASAL
AND NOW MOVING ON TO MICRO
NEEDLES.
WE HAVE DONE SINGLE DOSE
RABBITS IN WHAT WOULD BE
CONSIDERED HUMAN DOSE.
WE HAVE FORMULATION FOR
BEDSIDE AND HAVEDOWN EXTENSIVE
BIOSIMILAR.
AS AN' MUGS, WE CAN DO TWO
WEEKS AT 40 DEGREES AND SEE NO
LOSS OF EFFICACY AND WHERE ARE
WE IN SYNTHETIC MANUFACTURING?
WE HAVE THE PRECLINICAL AND
CLINICAL WHICH IS HAS A
FAVORABLE REGULATORY PATHWAY
AS A CHEMICAL ENTITY.
THANK YOU.
>>SO THE NEXT TALK WE HAVE IS
SELENE LEMOINE FROM
SWITZERLAND.
>>THANK YOU FOR THE
OPPORTUNITY TO PRESENT VFI
ADJUVANT PORTFOLIO.
I AM SELENE LEMOINE, HEAD OF
VFI LABORATORY IN SWITZERLAND.
SO TO START OFF, WE HAVE THE
FIRST POINT OF OPEN ACCESS.
WE WILL COME BACK AT A LATER
STAGE WITH MORE INFORMATION.
OTHERWISE IN OUR VFI ADJUVANT,
WE HAVE A FEW, WE HAVE SQ AND
LQ.
SQ IS A CHOLESTEROL ADJUTANT,
LQ IS A SAPONARIA EXTRACT AND
LMQ IS A SYNTHETIC TLR4 AND
THESE ARE IN DEVELOPMENT AND
WITH THE SUPPORT OF THE BILL &
MELINDA GATES FOUNDATION.
I HAVE ALREADY SAID IN
PREVIOUS PRESENTATIONS THERE
IS NOT ONE BEST ADJUVANT.
IN ORDER DIVERSIFY OUR
ADJUVANT PORTFOLIO, THESE CAN
BE LATE DEVELOPMENT WITH THE
GM P MANUFACTURE IN 2024.
SO COMING BACK TO THE
SYNTHETIC, IT IS AVAILABLE AT
GM P AND INDUSTRIAL SCALE AND
CURRENTLY MANUFACTURED WITH
700 MILLION DOSES.
IT IS PROVIDED BY SEPIVAC
ALREADY BY SEVERAL VACCINE
MANUFACTURERS TO BE ELEVATED
IN CLINICAL TRIALS.
FOR EXAMPLE, PHASE 2 IS
PRESENTLY ONGOING FOR THE
VACCINE CALLED PROVAC2
DEVELOPED BY OUR COLLEAGUES AT
THE UNIVERSITY OF TORONTO IN
CANADA.
NEXT SLIDE, PLEASE.
SO TODAY I HAVE A SHORT AMOUNT
OF TIME TO SHOW YOU SOME OF
OUR PRECLINICAL DATA.
FIRST I WOULD LIKE TO SHOW YOU
SOME DATA FROM THE TUBES LOWS
VACCINE WHICH IS A BCG VACCINE
DEVELOPED BY UNIVERSITY OF
OXFORD.
HERE YOU SEE THE CHALLENGE
DATA FOR MICE AND THE LMQ AND
SQ OBSERVED IN MICE.
WE ALSO HAVE THE IMPROVED
PROTECTION AND WITH HIV AND
AIDS, THERE IS HIGHER
NEUTRALIZATION TITERS WITH SW
SKP*E SQ.
IN THE SCOPE OF THE ADJUVANT
PROGRAM, WE ALTERED THE
ANTIGEN AND HERE WE SEE DATA
FOR THE SQ AND LMQ IN
CONNECTION WITH THE R21
ANTIGEN.
THE GRAPHIC WE SHOW HERE, VERY
RECENT DATA, NOT PUBLISHED YET
BUT WE HAVE PREVIOUS CHALLENGE
DATA IN INVESTIGATION WITHIN
MECHANISMS OF SQ AND LMQ
SUMMARIZED IN A PAPER WHICH
WILL SOON BE PUBLISHED IN A
PAPER WITH CELL REPORTS
MEDICINE.
WE HAVE MANY MORE
COLLABORATIONS AND PAPERS ON
DIFFERENT INDICATIONS.
SOME EXAMPLES ARE WITH STREP,
WITH MERS AND ALSO WITH
COVID-19 DEVELOPED AT MIT.
SO TAKE-HOME MESSAGES FOR
TODAY, I THINK IT HAS BEEN
REPEATED MULTIPLE TIMES BUT
ONE ADJUVANT DOES NOT WORK
ACROSS ALL COMPARISONS SO
LOOKING AT THE ADJUVANT IS
VERY IMPORTANT TO LOOK AT THE
TERPATION DATA WITH BOTH
ANIMAL AND CLINICAL DATA WE'RE
PREDICTING.
NEXT, PLEASE.
THANK YOU VERY MUCH FOR
LISTENING AND PLEASE REACH OUT
TO ME IF YOU WANT TO LEARN
MORE ABOUT THE VFI ADJUVANT.
>>THANK YOU VERY MUCH AND THE
POINT THAT HAS BEEN MADE OVER
AND OVER AGAIN, ONE ADJUVANT
IS NOT GOOD FOR ALL.
WE'RE COMING FULL CIRCLE WITH
THE NEXT PRESENTER,
CHRISTOPHER FOX FROM AAHI.
>>THANK YOU, WOLFGANG.
I REALLY ENJOYED ALL THE TALKS
TODAY.
A TOUGH ACT TO FOLLOW BUT ON
THIS FIRST SLIDE, WE WANT TO
GIVE YOU AN OVERVIEW OF OUR
FEATURE ADJUVANT FORMULATIONS
CURRENTLY IN THE VACCINE
COMPENDIUM AND THE ASSOCIATED
QR CODES.
LIKE MANY OF THE PREVIOUS
SPEAKERS, OUR PORTFOLIO IS
GENERATED BY MIXING AND
MATCHING DIFFERENT MOLECULAR
ADJUVANTS, MOSTLY TLLIGANDS OR
SAPONINS WITH THE FORMULATION
PLATFORM INCLUDING 'EM
PHULGSZ, LIP SOLES AND
ALUMINUM SALTS.
SO WE END UP WITH A BIT OF
ALPHABET SOUP, TENDS TO BE
DELAYED IN A COMMON WAY BUT
TRADITIONALLY THESE ARE THE
TLH4 WITH LIGANDS OR WITH
SAPONINS.
WE HAVE ALSO DEVELOPED NEXT
GENERATION SYSTEMS WITH
FORMULATIONS OF ALUMINUM SALT
AND HAVE A LONG HISTORY WHERE
WE TRIED TO ACCRUE THE
STABILITY PROPERTIES AND THAT
IS REPRESENTED BY NANOAL LUM.
SO ANOTHER WAY, NEXT SLIDE
PLEASE.
ANOTHER WAY TO LOOK AT THESE
DIFFERENT ADJUVANT SYSTEMS IS
THEIR CLINICAL DEVELOPMENT
PROJECT AND SO SEVERAL
THOUSAND PARTICIPANTS HAVE
RECEIVED VACCINES CONTAINING
OUR ADJUVANT SYSTEM AND THESE
ARE REPRESENTED HERE BOO
CLINICAL DEVELOPMENT STAGE AS
A PARTICULAR ADJUVANT
FORMULATION WHERE SQUALENE
RECEIVED THE MOST EXPERIENCE
BUT ALSO SOME OF OUR ALUM
FORMULATIONS AND SCREENINGS
WITH LIPOSOMES HAVE BEEN GIVEN
AS WELL.
THESE HAVE BEEN CLINICALLY
DERISKED AND MULTIPLE CLINICAL
TRIALS THROUGH MULTIPLE
GENERATIONS HAVE DEVELOPED OUR
DATABASE THAT SHOW THESE ARE
SUITABLE FOR NOT JUST HEALTHY
ADULTS BUT DIFFERENT
POPULATIONS.
WE ALSO HAVE A HANDFUL OF
EARLIER STAGE ADJUVANTS IN THE
DEVELOPMENT PROCESS WHICH ARE
ADDED HERE AND WILL BE ADDED
TO THE VACCINE COMPENDIUM IN
THE COMING YEARS.
NEXT SLIDE, PLEASE.
IN RECENT YEARS, WE HAVE
REALLY FOCUSED, ALTHOUGH WE
ARE DEVELOPING NEW ADJUVANTS,
WE PUT OUR PRIMARY FOCUS ON
PRACTICAL IMPROVEMENT FOR
EXISTING ADJUVANT ASSETS.
SO THESE ARE REPRESENTED BY
JUST THREE PUBLICATIONS.
SO SOME OF THE THINGS WE
REALLY FOCUSED ON IS PROCURING
SUSTAINABLE SUPPLY.
SO THE NONSQUALENE THROUGH THE
ANIMAL PROCESS AND THEN ON THE
OTHER HAND TO ENSURE VACCINES
CAN BE MADE AT SCALE AND
DISTRIBUTED.
IN TERMS OF INNOVATIVE
FORMULATION WORK, WE HAVE
POSED RECENTLY ON ADJUVANTS
THAT CAN BE USED FOR INTRANATE
SAG DELIVERIES AND THESE HAVE
BEEN DEVELOPED THROUGH THE IN
HOUSE R&D SUITE AND THEN
MAKING SURE THE VACCINE IS
STABLE, COMPLETING PHASE 1
TESTING EARLIER THIS YEAR
SHOWING US THE THERMAL STABLE
VERSION OF THE VACCINE IS AS
IMMUNOGENIC AND STABLE AS THE
NONSTABLE VERSION.
AND IN CONCLUSION, NEXT SLIDE,
JUST TO EMPHASIZE WE ARE
COMMITTED TO LOCAL CAPACITY
BUILDING AND MANUFACTURING OF
THE ADJUVANTS IN COUNTRIES,
THIS WAS HIGHLIGHTED EARLIER
TODAY BY PALO WITH BHUTAN IN
BRAZIL, OUR MISSION IS TO GET
THESE ADJUVANTS MADE LOCALLY
AND I WILL STOP THERE.
>>THANK YOU VERY MUCH.
I WOULD LIKE TO THANK ALL OF
THE SPEAKERS AND FOR STAYING
ON SCHEDULE.
I DO WANT TO POINT OUT THE
SUPPORT FROM NIAID AND WE CAN
DAN.
[INDISCERNIBLE]
BUT ALSO WANT TO THANK
SPECIFICALLY THE SDIR
CONFERENCE IN COPELAND
PERSONNEL --
[INDISCERNIBLE]
THE DEVELOPMENT OF MIMIC
VERSIONS TO MAKE SHE IS
ELEMENTS AND --
[INDISCERNIBLE]
AND WITH THAT, I WILL PASS IT
BACK TO ANNIE.
>>THANK YOU FOR ALL THAT
INFORMATION.
OUR LAST SPEAKER, LET'S SEE,
MARTIN FRIEDE.
>>IT WAS VERY NICE TO SEE THE
AMAZING WORK ALTOGETHER AND
THANK YOU FOR PICKING UP THE
QUESTIONS IN THE CHAT.
WHAT WAS AMAZING IS TO SEE ALL
THE PROGRESS THAT HAS BEEN
MADE.
I ENTERED THE PROGRAM A NUMBER
OF YEARS AGO AND IT WAS
PARTICULAR TO REMEMBER IN
THOSE DAYS, WE HAD NOT HEARD
ABOUT NEW ADJUVANTS SO IT IS A
HUGE STEP FORWARD WITH THE
ADJUVANTS SO WE HAVE TO FIGURE
OUT WHAT ADJUVANT WE HAVE IN
THE NEXT 30, 40 YEARS AND IT
HAS BEEN BEEN WITH VACCINES,
WHAT HAVE WE GOT ON OUR SHELF
AS OPPOSED TO WHAT CAN WE COME
UP WITH SO THIS IS HUGE
PARTICULARLY THE ROLE OF THE
ANTIGEN.
I CANNOT EMPHASIZE ENOUGH THAT
THESE ARE POWERFUL A VANITIES
PUTTING IT IN A WEAK VACCINE,
IT DOESN'T WORK.
YOU NEED A POWERFUL
ADJUTANT --
[INDISCERNIBLE]
[ ALMOST WHISPERING ]
SO ONE OF THE THINGS YOU DON'T
LEARN IN TEXTBOOKS, IT COMES
FROM EXPERIENCE.
SO FROM WHO, I WOULD SAY
EXPERIENCED FORMULATION,
SHARED INFORMATION, WRITE
PAPERS, REALLY UNDERSTAND THE
ASPECTS OF THE COMBINATIONS.
AND THEN AS A FINAL THOUGHT
WITH ADJUTANTS, WHAT IMPACT
MIGHT THIS MAKE.
SO WITH THE MICE, WE ARE
REALLY STUDYING MORE AND MORE
VACCINES COMING IN AND --
[INDISCERNIBLE]
SO TO GET WHAT WE CALL A FULL
VALUE ASSESSMENT WITH VACCINES
AND IF WE MAKE THOSE VACCINES
--
[INDISCERNIBLE]
SO I WOULD STOP THERE AND
THANK ANNIE WHO HAS DONE AN
AMAZING JOB AT THE NIH PULLING
THIS TOGETHER.
AND THEN FROM WHO AND THE BILL
& MELINDA GATES FOUNDATION, I
WOULD LIKE TO ANNOUNCE OUR
NEXT WEBINAR IN EARLY FEBRUARY
OF NEXT YEAR FOR THE NEXT
PHASE OF VACCINES.
THERE IS NOT ONLY A HUGE
AMOUNT OF POLICY WORK NEEDED
TO GENERATE ENOUGH INTEREST IN
THIS BUT --
[INDISCERNIBLE]
AND WITH THAT FROM ALL OF YOU,
FOR THE PARTICIPATION OF ALL
THE SPEAKERS, NIAID AND
EVERYBODY, THANKS VERY MUCH.