>> Good morning, everyone.
It is 10:00 a.m. This
is Dr. Amanda Cohn,
the Executive Secretary
of the Advisory Committee
for Immunization Practices.
I am going to go ahead and
turn it over to Dr. Romero
to bang his virtual gavel
and open the meeting.
>> Good morning, everyone.
Welcome to the August
26th, 2020 ACIP meeting.
Thank you for giving
up of your time.
This is another one
of our virtual meetings
open to the public.
So with that.
[ Gavel Pounding ]
I just knocked on the table,
if you couldn't hear that.
This meet is now open.
Back to Dr. Cohn.
>> Thank you, Dr. Romero.
So good morning and welcome
to the August 2020
virtual ACIP meeting.
Copies of the slides
that are being presented
at today's meeting are available
until 5:00 p.m. today
on the ACIP website.
These slides will be removed
from the website this afternoon.
Made 508 compliant.
And re-put up on the website
in the next week or two.
Additionally, slides
are available
through a share file link
for ACIP voting liaison
and ex officio members.
Next slide.
Next slide.
Slides presented at this
meeting will be posted
on the ACIP website in
the next couple of weeks.
Additionally, the live website,
webcast videos will
also be posted
on the ACIP website
approximately four weeks
after this meeting.
And minute meetings are posted
on the ACIP website generally
within 120 days of the meeting.
We have not yet posted minutes
from the July ACIP meeting.
But the videos are available.
Next slide.
This is for the ACIP voting
ex officio and liaison members
who are on the Zoom call.
Please mute your
lines at all times
until you're called
on for discussion.
When Dr. Romero opens the
meeting for discussion,
please virtually
raise your hand.
And during the discussion
period,
Dr. Romero will take
questions first
from the voting ACIP members.
And then from ex officio
member and liaison members.
We are going to stay on the
schedule per the meeting agenda.
So if we're running
early, we will break
until the next start
time on the agenda.
And we ask that everyone
on the Zoom open call,
please disable your video.
Next slide.
I want to call everyone's
attention
to the next two ACIP
virtual meeting dates.
These remain tentative in
that meetings may be added.
But we can assume that the
next meeting as of now is
on September 22nd, 2020.
Starting at 10:00 a.m.
and running likely
until 4:00 p.m. Eastern
Standard Time.
And we will be having a meeting
on October 28th and 29th, 2020.
This is our normally
scheduled ACIP meeting.
And during that meeting, we
will be able to discuss topics
that are not COVID related.
Next slide.
This meeting's oral and written
public comment processes are
designed to accommodate
increased public interest
in ACIP's work.
Maximize the opportunities
for comment.
Make public comment more
transparent and efficient.
And create a fair process
for assigning limited
oral public comment time.
Next slide.
Members of the ACIP agree
to forego participation
in certain activities related
to vaccines during their
tenure on the committee.
ACIP has issued limited conflict
of interest waivers to members
who conduct clinical
vaccine trials to serve
on data safety monitoring
boards.
These members are
prohibited from participating
in committee votes
related to those vaccines.
And regarding other vaccines,
if the concerned company member
may participate in discussions
with the provision
that he or she abstains
on all votes related to the
vaccines of that company.
At the beginning
of each meeting,
ACIP members state any
conflicts of interest.
At this meeting today there
are no votes scheduled.
So while ACIP members will
be stating their conflicts
of interest at the
beginning of the meeting.
There will be no vote occurring
where they would have to,
where they would be prohibited
from being part of the meeting.
Next slide.
So I'm now going to hand
it back over to Dr. Romero,
who's going to start
with roll call.
I'm going to shift
the direction slightly
from the last time
we did roll call.
For ACIP members, when
Dr. Romero calls you,
please state your name and
conflict of interest only.
Ex officio and liaison
members do not need
to state their conflict of
interest or affiliation.
Dr. Romero will call
the organization.
And the member who is
representing that organization,
please state your name.
Dr. Romero.
>> Thank you Dr. Cohn.
I'll begin as Jose Romero.
No conflicts of interest.
Dr. Atmar.
>> Robert Atmar.
I'm a codirector of the
Clinical Operations Unit
of the NIH-funded Infectious
Diseases Clinical Research
Consortium that is working with
the COVID-19 Prevention Network
to evaluate SARS-CoV-2
vaccine candidates
in Phase 3 clinical trials.
Including the vaccine
produced Moderna
that will be discussed
in today's meeting.
Over.
>> Thank you.
Dr. Ault.
>> Kevin Ault.
No conflict.
>> Ms. Bahta.
>> Lynn Bahta.
No conflict.
>> Dr. Bell.
>> Beth Bell.
No conflict.
>> Dr. Bernstein.
>> Hank Bernstein.
No conflict.
>> Dr. Frey.
>> Hello, I am a, we
have a VTU study here.
St. Louis University
has a vaccine treatment
evaluation unit.
Part of the infectious
diseases consortium
for research, clinical research.
And I will be conducting
COVID-19 trials.
>> Thank you.
Dr. Hunter.
>> Paul Hunter.
[ Inaudible Comment ]
Project related to
pneumococcal vaccines.
Thanks.
>> Dr. Lee.
>> Grace Lee.
No conflicts.
>> Ms. McNally.
>> Veronica McNally.
>> Any conflicts, Ms. McNally?
>> No conflicts.
>> Thank you.
Dr. Poehling.
Dr. Poehling.
>> Kathy Poehling.
No conflicts.
>> Thank you.
Dr. Sanchez.
>> Pablo Sanchez.
[ Inaudible Comment ]
>> Thank you.
Dr. Szilagyi.
>> Peter Szilagyi.
No conflicts.
>> Dr. Talbot.
>> Keipp Talbot.
No conflicts.
>> That ends the roll
call of the ACIP members.
I will now begin the roll call
for ex officio representatives.
>> Before we start the roll
call for ex officio members,
we are hearing a lot
of echo on the line.
I'm, can I please
ask for anybody
who is not speaking
to mute your line.
Thank you.
>> I'll begin with ex
officio representatives.
Centers for Medicaid,
Medicare-Medicaid Services.
>> Mary Beth Hance.
>> Thank you.
Department of Defense.
>> Bryan Schumacher.
>> Thank you.
Department of Veterans Affairs.
>> Jane Kim.
>> Thank you.
Food and Drug Administration.
>> Doran Fink
>> Thank you.
Health Resources
Services Administration.
>> Mary Rubin.
>> Thank you.
Indian Health Service.
>> Thomas Weiser.
>> Thank you.
Office of Infectious
Diseases and HIV/AID Policy.
Office of Infectious
Disease and HIV/AID Policy.
>> Tammy Beckham.
>> Thank you.
National Institutes of Health.
>> John Beigel.
>> Thank you.
I'll now move onto the
liaison representatives.
Again, state your name only.
No need for stating
conflict of interest.
American Academy of
Family Physicians.
>> Pamela Rockwell.
>> American Academy
of Pediatrics.
>> Yvonne Maldonado.
>> American Academy of
Physicians Assistants.
>> Marie-Michele Leger.
>> American College
of Health Association.
>> Sharon McMullen.
>> American College of Midwives.
>> Carol Hayes.
>> American College of
Obstetricians and Gynecologists.
American College of
Obstetricians and Gynecologists.
I'll come back to them.
American College of Physicians.
>> Jason Goldman.
>> American Geriatrics Society.
>> Ken Schmader.
>> American Immunization
Registry Association.
>> Rebecca Coyle.
>> American Medical Association.
>> Sandra Fryhofer,
American Medical Association.
>> American Nurses Association.
>> Chad Rittle.
>> American Osteopathic
Association.
American Osteopathic
Association.
I'll come back.
>> Stan.
>> I'm sorry.
>> Grogg.
>> Thank you.
American Pharmacists
Association.
>> Steve Foster.
>> Association of
Immunization managers.
>> Chris Finley.
>> Association for Prevention,
Teaching and Research.
>> Paul McKinney.
>> Association of State and
Territorial Health Officers.
Association of State and
Territorial Health Officers.
Officials.
Sorry, forgive me.
I'll come back.
>> Biotechnology
Industry Organization.
>> Phyllis Arthur.
>> Council of State and
Territorial Epidemiologists.
>> Christine Hahn.
>> Canadian National Advisory
Committee on Immunization.
Canadian National Advisory
Committee on Immunization.
I'll return.
Infectious Diseases
Society of America.
>> Carol Baker.
>> International Society
for Travel Medicine.
>> Elizabeth Barnett.
>> National Association
of County
and City Health Officials.
>> Matt Zahn.
>> National Association of
Pediatric Nurse Practitioners.
National Association of
Pediatric Nurse Practitioners.
>> Patsy Stinchfield.
>> National Foundation
for Infectious Disease.
>> William Schaffner.
>> National Medical Association.
>> Pat Whitley-Williams.
>> Pediatric Infectious
Diseases Society.
>> Mark Sawyer.
>> Pharmaceutical Research
and Manufacturers of America.
>> Corey Robertson.
>> Society for Adolescent
Health and Medicine.
>> Amy Middleman.
>> Society for Health
Adolescent Health and Medicine.
>> Amy Middleman.
>> Yes, thank you.
Sorry. Society for Healthcare
Epidemiology of America.
>> Marci Drees.
>> Okay. Let me go back around.
American College of
Obstetricians and Gynecologists.
American Osteopathic
Association.
Association of State and
Territorial Health Officials.
That completes the roll call.
Thank you very much.
I will return it back
over to Dr. Cohn.
>> Great. Thank you, everybody.
We did forget to introduce
Dr. Nancy Messonnier
who is here as well.
From the, representing
the Centers
for Disease Control
and Prevention.
We know that we are
having some echos
that are coming from the room.
And we are working
on that as we speak.
We are going to mute
everyone on the phone except
for the first speaker.
And we apologize for
the inconvenience.
But we are working on it.
Thank you.
Dr. Romero, you're ready to move
to the first part of the agenda?
>> I am. So we're going to talk
about coronavirus
disease in 2019.
Vaccines. With an
introduction by Dr. Bell.
Dr. Bell, please.
>> Thank you, Dr. Romero.
And welcome to everyone.
There are the slides.
Thank you.
I'm hoping that I'm not
echoing as I'm speaking.
It will be hard to
understand me if I am.
Could I have the
next slide, please.
Thank you.
Over 200 COVID-19 vaccines are
currently under development.
Including four in
clinical trials
in the United States
at the moment.
The ACIP has been responding
to this ongoing pandemic
and accelerated vaccine
development through scheduling
of monthly emergency
ACIP meetings.
During which we have
the opportunity
to discuss evolving epidemiology
and other relevant data.
And hear about the vaccines
as they're being developed.
At the July 29th meeting,
to remind all of you.
We reviewed the status
of COVID-19 clinical,
vaccine clinical trials.
We discussed COVID-19
vaccine safety considerations.
We spent some time
considering the differences
between FDA licensure
versus emergency
use authorization
of COVID-19 vaccine.
We discussed vaccine
implementation.
We reviewed the epidemiology of
COVID-19 in essential workers.
Including healthcare personnel.
We discussed our ongoing work on
COVID-19 vaccine prioritization.
And discussed how the work group
was approaching these issues.
And we reviewed the evidence
to recommendations framework.
Next.
Our COVID-19 vaccine
group meets weekly.
And we have been meeting weekly
since the last ACIP meeting.
During August, we
covered a review
of COVID-19 epidemiology
on at-risk groups.
Including American Indian,
Alaska native populations.
And individuals with
underlying medical conditions.
We heard from manufacturers.
And discussed the clinical
development program
for two mRNA vaccines.
Including data from Phase
1-2 clinical trials.
And plans for Phase
3 clinical trials.
We'll be hearing from
these manufacturers today.
We discussed models
that have been developed
that model allocation strategies
to inform initial
COVID-19 vaccine supply.
We reviewed initial COVID-19
vaccine distribution scenarios.
And we continued
our work focusing
on vaccine prioritization
considerations.
Especially for initial doses.
Next. On today's agenda,
we will be hearing
from clinical development
of mRNA-1273
by Dr. Jacqueline
Miller from the Moderna.
We will be hearing about the
Pfizer/BioNTech COVID-19 mRNA
vaccine clinical development
from Dr. Nicholas Kitchin.
We will discuss an overview
of post-marketing
safety surveillance
from Dr. Tom Shimabukuro.
We will hear from Dr.
Nanny McClung from the CDC
about the epidemiology of the
COVID-19 among individuals
of increased risk
of COVID-19 disease.
We will hear from
Dr. Rachel Slayton
about modeling allocation
strategies
for the initial COVID-19
vaccine supply.
A work group, sort of the
work group interpretation
of our current situation.
And prioritization and
work group next steps
from Dr. Kathleen Dooling.
Next, please.
I wanted to spend one
more moment talking
about considerations
for prioritization
of COVID-19 vaccines,
as I think,
as more information
has become available.
The work group has been able
to advance our thinking
on this topic.
With a view towards sort of
fulfilling our obligations
to issue some guidance
and recommendations.
So in today's session we
will focus on individuals
at increased risk of COVID-19.
Including underlying
medical conditions and age.
Then we will review the
four priority groups
for consideration of allocation
of initial COVID-19 vaccine.
We will now have heard
in some detail about each
of these four groups
at ACIP meetings.
And, of course, also
in the work group.
In the September session,
our plans are to focus
on the epidemiology of risk of
COVID-19 by race and ethnicity.
To review other published
prioritization frameworks
that may have been
completed by that time.
And we will be looking
to a possible vote
on an interim prioritization
schema for allocation
of initial COVID-19 vaccine when
it's available in limited doses.
Next, please.
So I always like to
take this opportunity
to show the work group members.
Including the ACIP members.
The ex officio members.
Many liaisons.
And the CDC co-leads
to whom we are in debt.
As well as our consultants
who are absolutely
pivotal to our work.
And next. Here's a list of
all the CDC participants
who help us understand the
data that becomes available.
And I think that's the
end of my presentation.
I want to thank you
all for joining.
And look forward to
[inaudible] meeting.
>> Thank you very
much, Dr. Bell.
So let me ask Dr.
Miller from Moderna
to please present the
mRNA-1273 clinical development.
Dr. Miller, please.
>> Thank you, Doctor.
Apologies.
Thank you very much.
My name is Jacqueline Miller.
And I am the therapeutic
area head
for infectious diseases
at Moderna.
And on behalf of Moderna, I'd
really like to thank the ACIP
and the working group
for the opportunity
to give you this update.
In our Phase 1 clinical
data and Phase 2,
Phase 3 clinical trial plan.
Next slide, please.
This slide is the standard
forward-looking statements
and disclaimer slide.
Next slide, please.
So mRNA-1273 is a vaccine
intended for protection
against the SARS-CoV2 virus.
It comprises a messenger RNA
sequence, single sequence
against the spike protein.
And that protein has two
proline substitutions.
And, therefore, the
protein is called F-2P.
There's two proline
substitutions.
[inaudible] the messenger,
the translated protein
in the pre-fusion confirmation.
Which is the most
immunogenic form.
The messenger RNA is delivered
via lipid nanoparticle,
targeting the antigen
presenting cells.
Including dendritic
cells and monocytes.
Once the messenger
RNA is delivered,
the ribosome translates
that messenger RNA
into the SARS-CoV-2 protein.
It naturally assembles into its
wild-type trimeric confirmation.
And then is self-surface
expressed.
The vaccine is 100
microgram dose.
And I will describe some
of the dose ranging data
in the slides that follow.
In addition, the vaccine is
a two-dose schedule given
at 28 days apart.
The vaccine is shipped and
stored at minus 20 degrees.
And then is able to be stored
at the point of care at 2
to 8 degrees in the
refrigerator.
Next slide, please.
So first I'd like to give
you an overall summary
of the preclinical data that
enabled us to progress forward
with clinical development.
In collaboration with the
Vaccine Research Center
at the NIH, a robust preclinical
data package has been compiled
in mice and nonhuman primates.
In both species robust
neutralizing antibodies have
been observed to be induced.
And these neutralizing
antibodies led to protection
against lung challenge
in the mice.
And pulmonary and nasal
challenge in nonhuman primates.
In addition, after challenge
there's no indication
of enhanced respiratory
disease on one pathology
after viral challenge.
Even when slower and
sub-protective doses
of messenger RNA-1273 are used.
Giving us reassurance into,
going into clinical development
regarding vaccine-enhanced
respiratory disease.
And, finally, a Th1
dominant phenotype
of CD4 four cells has been
induced in both mice and NHPs.
So with these data we had
discussed with FDA progressing
into our clinical
development program.
Which is detailed on
the next slide, please.
So this is a program that has
advanced relatively quickly
over the last seven
months or so.
And it's really the messenger
RNA platform technology has
enabled that along with frequent
reviews of data with the FDA.
Our first time in human study,
which has been sponsored
by the NIH was initiated
in March.
And continues to be ongoing.
And the data I will be
reviewing for you today comes
from both published
data last July
in adults 18 to 55 year olds.
As well as older adult cohorts
who are 56 to 70 years of age.
And above 71 years of age.
Then I'll describe
to you the Phase 2
and Phase 3 study designs.
Both of which are funded
by our partners Catharta
[assumed spelling].
The Phase 2 study initiated in
May and enrollment is complete.
And the Phase 3 study
started on July 27th.
Additional considerations for
the clinical development program
in the future will be in
pediatric populations.
And women in immunocompromised
populations.
Next slide.
So now I'd like to describe
to you the study design
for the Phase 1 clinical
trial that I'll describe
in these subsequent slides.
So, again, this is an
NIH-sponsored Phase 1 safety
and dose ranging study
that was conducted
in three different age cohorts.
So 18 to 55.
56 to 70. And greater
than 71 years of age.
The initial plan was to
evaluate three dose levels
in all three age strata
with 25 micrograms.
100 micrograms.
And 250 micrograms in a
sequential meaner with stops
for safety in between.
A fever to 39.6 degrees Celsius
was observed in a recipient 18
to 55 years of age with
the 250-microgram dose.
And, therefore, the 25 and 100
microgram doses were the ones
continued into the two
subsequent older-age cohorts.
And then, finally,
three additional
cohorts have been added
to evaluate the vaccine
at 50 micrograms.
This study is currently
fully enrolled.
And in its follow-up phase.
So these subjects were primarily
healthy males and females
above 18 years of age.
And we enrolled all
comers with respect
to their baseline
SARS-CoV-2 serostatus.
Although subjects that
described a past medical history
of COVID-19 disease
were excluded.
Safety endpoints
include adverse reactions
for seven days after
each injection.
As well as unsolicited
adverse events within 20 days
after each vaccination.
Serious adverse events
and medically attended
adverse events will be followed
through the entire
duration of the study.
And the immunogenicity assays
that are being evaluated
in this study include the ELISA
pseudo-neutralization assay.
That is the primary assessment
for neutralizing
antibodies moving forward
in the development plan.
Live virus neutralization
in an intracellular cytokine
staining assay for CD4 T-cell.
And, again, the subjects
will be followed
for approximately one year
after their final vaccination.
Next slide, please.
So I described to you that
the 250-microgram dose was
interrupted due to a
single fever observed
in a participant 18
to 55 years of age.
Now I'd like to describe for you
why the 100-microgram dose has
been selected for further
clinical development.
What I'm showing you on this
slide are the neutralization
antibody titers with the
pseudo-neutralization assay,
pseudo-virus neutralization
assay.
However, the conclusions
are similar
with the other assays
investigated.
So what you see in the graph,
moving left to right,
are the 25-microgram.
100-microgram.
And 250-microgram doses in the
subjects 18 to 55 years of age.
Highlighted in pink are
the middle two quartiles
of a range of convalescent sera.
So these are 41 subjects who
were tested after presenting
with symptoms of
COVID-19 disease.
And what you can see
from the slides is
as of day 14 post-dose 2,
neutralizing antibodies
were observed
in all participants
at all dose levels.
However, the lowest
responses were seen
at the 25-microgram dose.
So the subjects in the 100
and 250-microgram dose groups,
the range of antibody
titers was in the upper half
of range of convalescent sera.
And so the higher
antibodies titers observed
with 100-microgram dose
versus the 25-microgram dose
is the reason for selection
of that dose moving forward.
Next slide, please.
So this slide now
depicts the safety data
with the 100-microgram dose in
all three of the age strata.
18 to 55. 56 to 70.
And greater than
71 years of age.
And on the bar graph you see
in gray the Grade 1 reactions.
Grade 2 are in blue.
And Grade 3 are in orange.
The vaccine was well
tolerated across age groups
with injection site pain.
And then the solicited
symptoms of fatigue.
Chills. Headache.
And myalgia being the most
frequently reported symptoms.
There were more reports observed
after the second
dose of vaccination.
But there was no increase
in reactogenicity observed
in the older age cohort.
The systems, symptoms
were primarily mild
to moderate in severity.
And the majority of
these symptoms resolved
within two days.
Next slide, please.
So now I'd like to take you
through the immunogenicity data
for the three different
age strata.
And now on this slide, what
you see are binding antibodies
that have been measured
by an ELISA assay
across the three age groups.
And, again, 18 to
55 at the left.
56 to 70 in the middle.
And greater than 71 years
of age on the right.
Again, highlighted in pink
are the middle two quartiles
of the range of convalescent
sera.
So with this two-dose series,
100 micrograms seroconverted
all subjects
after the first dose of vaccine.
And the area under the curve
also exceeded the median
of the convalescent sera.
After the second dose, all
age groups are equivalent
to the higher range of titers
of the convalescent sera
in the upper quartile
of the dose.
And, importantly, these results
are consistent regardless
of age stratum.
Next slide, please.
So now on this slide you
see, again, the 18 to 55.
56 to 70. And over 71
years of age presented
in the pseudo-neutralization
assay.
So these are the
neutralizing antibody titers.
And, once again,
after the second dose,
we note pseudo-neutralization
antibody titers
in all participants.
Including the upper age
quartile, upper age range.
The titers were comparable
across the three age strata.
And I've included the geometric
mean titers in order for you
to be able to observe
the titers [inaudible].
And in all age groups,
the median tighter was
above the median of
the convalescent sera
at day 57 post-dose 2.
So that's one month post-dose 2.
Next slide, please.
So, finally, I'd to review
the CD4 positive T-cell data
that were generated in the three
age strata in the Phase 1 study.
So this is looking at
the CD4 T-cell response.
And it's looking at the
Th1 phenotype as measured
by elaboration of
interferon-gamma.
IL2. And TNF-alpha.
And similar to the
humoral immunity assays,
the CD4 Th1 T-cells
were detected
across the three age stratum.
The Th2 phenotype was rare.
And the data are not
shown in the slide.
But they can be seen
in the Jackson publication
for the 18 to 65.
And so with that, I'd like
to really thank the NIH
for allowing us to
present these data.
In particular, the data
in the older age cohorts
that have not yet not published.
Next slide, please.
So now I'm going to shift
gears and give you an overview
of our ongoing clinical
development program.
We have two additional
studies ongoing.
The first is a Phase 2 study
that is funded by BARDA
and sponsored by Moderna.
Which is evaluating the safety
and immunogenicity
of two dose levels.
50 micrograms and
100 micrograms.
We've enrolled two cohorts.
The first cohort, 18 to
less than 55 years of age.
And then the second cohort
greater than 55 years of age.
Both of those cohorts
include 300 subjects.
And amongst those 300 subjects,
100 subjects each will
receive 50 micrograms.
100 micrograms.
Or placebo at Day 1 and Day 29.
Again, these are healthy
males and females.
And we have enrolled
all comers with respect
to baseline SARS-CoV-2 status.
Safety endpoints are comparable
to the ones I described
for the Phase 1 study.
And we will be investigating
the ELISA assay
and the neutralization
antibodies as generated
by the pseudo-virus
neutralization assay
in the Phase 2 study.
The follow-up will be
approximately one year
after the second dose
for all subjects.
And this study is
now fully enrolled.
Dose 2 has been administered
to the entire population.
And the subjects are
undergoing their [inaudible]
vaccination follow-up.
Next slide, please.
So now I'd like to talk about
the COVE study.
Which stands for the COVID-19
Efficacy and Safety Study.
This is our pivotal
Phase 3 efficacy safety
and immunogenicity study.
Which will ultimately
enroll 30,000 subjects.
This is a study that
is conducted
through multiple partnerships.
Including BARDA funding.
And the partnership of NIAD.
And the COVID-19
Prevention Network.
It is a Phase 3 study that
will investigate the safety,
efficacy, immunogenicity
in subjects who are either
under 65 years and not at risk.
That will comprise
approximately 60
to 75 percent of the population.
Those over 65 years of age and
combined with a cohort younger
than of 65 years of age
who are at increased risk
for complications of COVID-19.
So these two strata,
the older age cohort
and those younger subjects
with comorbid conditions,
will comprise at least 25
percent and up to 40 percent
of the study population.
And so this was really designed
in mind with generating results
that are generalizable to
the U.S. population that is
at risk for COVID-19 disease.
The study started on July 27th.
And as of Friday last week,
there were over 13,000
subjects enrolled.
So subjects will be
randomized one to one
to receive either 100 micrograms
of vaccine or placebo.
And, again, these subjects
are all comers with respect
to their baseline
SARS-CoV-2 serostatus.
The study has two
co-primary objectives.
The first is to demonstrate
the efficacy of mRNA-1273
to prevent COVID-19 disease.
And I will be providing
these case definitions
in the slide that follows.
And the second is to
further evaluate the safety
and reactogenicity profile
of the two dose regimens
of mRNA-1273.
This study will last for
approximately two years
after the second
vaccination for each subject.
And the intent is for safety
and efficacy follow-up.
Next slide, please.
So the case definition to
define COVID-19 disease
for the primary analysis
in the COVE study was
that the participants must have
experienced either two groups
of, two of the listed
systemic symptoms.
Fever. Chills.
Myalgia. Headache.
Sore throat.
Or new smell and
taste disorders.
Or one respiratory symptom.
Cough. Shortness of breath.
Difficulty breathing.
Or clinical or radiographical
evidence of pneumonia.
And the participant
must also have
at least one nasopharyngeal
swab, nasal swab
or saliva sample positive
for SARS-CoV-2 RT-PCR.
And the preference is for
the nasopharyngeal swab taken
in the clinic.
But some allowance has been made
for subjects who may be too sick
to travel to the clinic.
The primary analysis
will be conducted
in seronegative subjects.
So those who are initially
SARS-CoV-2 baseline
serostatus negative.
And cases begin to accrue at
day 14 after dose 2 aligned
with the immunogenicity data I
presented for the Phase 1 study.
Next slide, please.
So I would like to take a moment
to talk about an initiative
that I'm quite proud
of at Moderna.
So we have brought
together a diversity
and inclusion advisory
committee.
And the purpose of
this committee is
to help us achieve our goal
to enroll a study population
that is representative
of the racial demography
in the U.S. We are
committed also
to transparency in
this initiative.
And if you are interested in
weekly updates for enrollment
as well as current
minority enrollment status,
you can find those at
the Moderna web page,
if you click on the COVE study.
So currently the study has
enrolled 18 percent minority.
And with the help
of our diversity
and inclusion advisory
committee,
we hope to improve
upon those numbers.
This committee is helping
us review enrollment race
and ethnicity.
Helping us review and
evaluate outreach activities.
Helping give advice
on strategies
so we ensure participation of
individuals from communities
who are deeply impacted
by COVID-19.
And supporting the
development and implementation
of retention strategies in
the trial for these subjects.
And so thanks goes out to all
of our collaborators
on this committee.
Next slide, please.
So, finally, a note on the
limitations of research.
While the data I have shown you
are very encouraging in terms
of the immunogenicity
of the vaccine,
they are at the moment limited
and in a fairly homogeneous
population.
We also need to think about how
we will evaluate the vaccine
in pediatric subjects.
Pregnant women.
And immunocompromised patients.
The ongoing COVE study will
provide significantly more data
both in healthy adult subjects
as well as in older-age cohorts
and subjects with
preexisting comorbidity.
Next slide, please.
So in summary, the messenger
RNA-1273 vaccine encodes the
pre-fusion stabilized
spike protein
with the two proline
substitutions
in a lipid nanoparticle
dispersion.
Which is designed for delivery
to the antigen presenting
cells of the lymph nodes.
Our preclinical data package
has demonstrated induction
of neutralizing antibodies
and protection
against viral challenge in
mice and nonhuman primates.
The interim data from the
Phase 1 study indicates
that a 100-microgram dose
of vaccine is generally
well-tolerated
across the age strata.
Solicited symptoms mostly
mild to moderate in severity.
And self-limited in duration.
The vaccine has been observed to
induce neutralizing antibodies
in the upper half of the range
of convalescent serum
across age strata.
With the induction of Th1
bias CD4 positive T-cells.
And our Phase 2 and Phase
3 COVE are study underway.
I look forward to
providing you updates
on our progress at
future meetings.
And then final slide, please.
I'd like to end with a
thank you and acknowledgment
with all of our collaborators.
It really has required a village
to bring the project
to this point.
And I want to call
out, in particular,
our funding partner BARDA.
The clinical research
partnership ship
that we have had with NIAD.
As well as the Vaccine
Research Center.
And the COVID-19
Prevention Network.
In particular, really
strong thanks
to our study investigators and
all of the study personnel.
They're working so hard
to deliver this study.
And then, finally, the subjects
who agreed to participate.
They really are the true
heroes of this endeavor.
And none of this would be
without their trust
and participation.
So with that, I'd like
to thank you, again,
for the opportunity
to share these data.
And I'm very happy to take
any questions you might have.
>> Thank you very
much, Dr. Miller.
Open for discussion.
>> Hey, this is Keipp.
I had.
>> Dr. Hunter, please.
>> Hi, yes.
Paul Hunter.
I just had a concern that,
if convalescent titers
were collected later
than postvaccination titers,
they might be setting
a lower target
than we need from a vaccine.
If I'm understanding how
things work correctly.
And so I'm wondering on average,
how long after infection
were the convalescent
titers collected?
Especially compared to the
postvaccination titers.
>> Yeah, thanks for
your question.
On the convalescent titers were
collected between 23 and 60 days
after the onset of symptoms.
And so really represent
the range of time points
that I presented
in the slide deck.
>> Thank you, Dr. Poehling.
>> Hi, Kathy Poehling.
First of all, thank
you for presenting.
And the enormous amount of
work that has been done.
And presenting it so clearly.
I wanted to give you
an opportunity to talk.
One of the things that I heard
was how we have a predominance
of Th1 response.
And rarely have Th2.
Would you mind elaborating
on why that's so important?
>> Yes. Thank you
for that opportunity.
So the Th1 responses are
reassuring to us in terms
of the potential risk
for vaccine-associated
enhanced respiratory disease.
And the reason for
that is in the past
with other respiratory viruses,
such as respiratory syncytial
virus and measles virus.
When children have been observed
to have enhanced disease
after vaccinations.
When their T-cells
were examined,
they had a preponderance
of the Th2 phenotypes.
So elaborating cytokines
such as IL4 and IL13.
By seeing Th1, both in
our animal models as well
as in our Phase 1 clinical
trial, it was helpful
to be reassuring to begin
clinical development.
Especially because our clinical
development is occurring
with relatively rapid
enrollment.
But I should mention that
we're certainly not relying
on that information.
We have a DSMB for
both the Phase 2 study.
Which is supported by Moderna.
And Phase 3 study.
Which is supported by NIAD.
And the DSMBs are reviewing
the reported safety information
throughout the trial.
And monitoring specifically
for vaccine associated
enhanced respiratory disease.
>> Dr. Kimberlin.
>> David Kimberlin,
AAP Red Book.
Are you, along the lines
of kind of thinking
about the inflammation that
goes along with natural disease.
Are you measuring markers of
inflammation in the studies?
>> So the markers
of inflammation have really been
measured in the Phase 1 study
in order to expedite
the enrollment
and generation of data.
The assays in the Phase 3 study
have been limited to the ELISA
and the pseudo-neutralization
assay.
However, detailed information
is collected on the patients
who ultimately do test
positive for COVID-19.
And while we're not specifically
looking at cytokines,
they will be followed
closely on a daily basis
through tele-medicine visits.
And hopefully we can then
capture the symptomatic data
and characterize what we see.
>> Dr. Talbot.
>> Yes. Can you talk
a little bit
about how this vaccine
will be stored and used.
And what kind of
requirements for refrigeration
or room temperature
are required?
>> Sure. And what I
am going to present
to you are the stability
data that are available now.
But as much of the development
program continues in parallel,
we also continue to
generate stability data.
And so these conditions
will be updated
as the stability data
allow them to be.
So at the time of launch,
the vaccine will be shipped
and stored up to six
months at minus 20 degrees.
Then the vaccine can
be kept at 2 to 8
for seven days in
the refrigerator.
And that's really
intended for sites
that do not have the
freezer capacity.
The vaccine will be presented
in a ten-dose vial
without preservative.
And so, once the
vaccine is thawed
and the rubber seal is
initially punctured,
there's a six-hour
window available
to administer the
remaining doses.
>> Dr. Fryhofer.
>> Yes, this is a
follow-up question
about the vaccine-enhanced
disease.
Earlier in your presentation,
when you showed a slide
of preclinical data support
human clinical trials
with mRNA-1273.
There was a statement that
there was no indication
of enhanced respiratory disease
after viral challenge even
when the lowest doses
of mRNA-1273 are used.
Can you explain that a little
more thoroughly for me, please.
Thank you.
>> Sure. So in both the mice
and the nonhuman primates,
lung pathology was examined
after viral challenge.
And the viral challenge
in the mice was at a dose
of 5 times 10 to the fifth.
In the nonhuman primates it was
7.6 times 10 to the fifth PSUs.
And when the animals
were sacrificed,
no inflammation was
seen in the lungs.
Even down to doses
of 0.1 micrograms.
So, you know, while we
used the 100 micrograms,
that statement was meant
to reflect the fact
that through all of the doses
tested in the animal models,
we did not see lung pathology.
>> Dr. Sanchez, my apologies.
I skipped you.
Dr. Sanchez.
>> No problem.
Now, that was great.
It's very exciting data.
I was just wondering actually
the issue that's come up now
with reinfection in
those three individuals.
And you're monitoring
these individuals
in the Phase 3 study
through 24 months.
And how, what are your plans
for addressing that in terms
of beyond meeting or not
meeting the primary endpoint?
>> So please let me know
if I haven't understood
the question specifically.
But maybe it would help to
know that we will follow
and capture every
case with COVID-19.
So not just the first cases of
COVID-19 in the study conduct.
And depending on how many
infections we would observe,
I mean, we are intending
on looking at the request
of our DSMB at cases that
occur more than once.
We also will be looking
at antibody persistence
at various time points
through the trial.
And we'll be evaluating also
by looking at the Phase 1
and Phase 2 data
very carefully to see
if there's a certain moment
at which it would make sense
to evaluate a booster dose.
>> Thank you.
And I presume you would
be doing sequencing
of follow-up isolates or?
>> So sequenced to the,
well, we don't plan
to actually sequence the
individual isolates now.
But it's definitely
an interesting idea.
And I'm sure it will now
generate some discussion
with our partners.
We will be testing the
individuals for RT-PCR
because that's how we will
define all of the cases.
We are investigating
for viral shedding
when individuals are
actually positive by RT-PCR.
So every three days or so
for the first 14 days subjects
will either come into the clinic
for a nasopharyngeal swab.
Or they'll submit
a salivary sample.
And so there will be viral
shedding samples on which
that kind of work could be done.
>> Thank you.
>> Dr. Szilagyi.
>> Yes, Peter Szilagyi.
Thank you for this
incredible work
and very clear presentation.
I have a couple questions
about the target population
for the Phase 3 trial.
As you know, there's been a lot
of national interest to ensure
that the target population
is reflective
of the U.S. population.
And I appreciate the
advisory committee
and the regular reviews
of race and ethnicity.
But my question is, are there
targets or internal goals
for race and ethnicity?
And also for age group above 65?
So, for example, above 75?
And could you also define race
and ethnicity a little bit more?
Are there any goals or targets
beyond black and Hispanic?
>> So thank you for
your question.
And I'm going to try to
give a more thorough picture
of how we are monitoring
for race and ethnicity.
And this is definitely
an evolving picture.
I would say it is
the predominant topic
of the weekly meetings that we
have with operation warp speed.
So our goal has always
been to enroll a study
that is representative of the
demography in the U.S. And,
you know, we know that in
the past it's been difficult
actually to reach that goal.
And very few vaccines trials
have been able to do it.
So the outreach activities
started early on.
There are not specific
targets at the moment.
Although they get
discussed on a regular basis.
And if there is an update
to that information,
I'll not happy to provide it.
African-Americans
and Hispanic-Americans are
certainly a focus of the trial.
But we are also tracking the
enrollment of Asian-Americans.
And of Native Americans.
Again, because these are
very important groups also
at risk for COVID-19 disease.
And as I said, recognizing
that there is so much interest
in how the diversity
enrollment is progressing.
We have this week made a
commitment to be transparent
about the progress
of our enrollment.
So we are going to
update on our website
on a weekly basis
this information.
Including the percentage
of nonwhite enrollment
in the trial.
>> I really appreciate that.
And also my, well, first of
all, I feel that confidence
in any vaccine will be
related to the representative
of the population that has been
enrolled in Phase 3 trials.
So I think this is
really, really important.
Could you comment
on the question
about older age groups over 75?
>> Yes, sorry about that.
So there's not a
specific stratification
for older adults above age 75.
Not a specific proportion.
But I can tell that you we have
had patients already enrolled
in their 90s.
So the hope is at the end there
will be a reflective spread
of demography there as well.
But so far that has actually
not been, the older-age cohort
in itself has not been
a challenge to enroll.
>> Thank you very much.
I recognize the challenge in
enrolling minority populations.
And I appreciate all
the work you're doing.
>> Well, thank you
very much for that.
And we fully agree that
this is absolutely critical
to really assess the
value of the vaccine.
>> Dr. Hayes.
>> Yes, could you please address
any adjuvants that you're using
in the multi-dose vial
of the current vaccine?
>> So mRNA-1273 does not
contain any adjuvants.
It is purely the messenger RNA
in the lipid nanoparticle
dispersion.
And the excipients are limited
to [inaudible] sucrose
and acetate.
>> That's wonderful.
So that means that
you anticipate
that this vaccine will
be, this is the vaccine
that you will use clinical
trials for pregnant women?
>> Yes, that is the intent.
And I should say that
recognizing the importance
of COVID-19 disease
in pregnant women.
We are evaluating the potential
for further evaluation.
I think what we would like to
see is a larger safety database
in nonpregnant adults before
really engaging in that work.
But I would mention that in the
Phase 3 clinical trial there is
an intent to report
all pregnancies
in the clinical study report.
Nonetheless, women are
getting pregnancy tests before
they're vaccinated.
So we anticipate that
number to be small.
But recognizing the importance,
and we'll be further evaluating
as clinical developments
[inaudible].
>> Thank you.
>> Dr. Sanchez, your
hand is still up.
Do you have additional
questions?
>> I'm sorry, no.
No.
>> Dr. Fryhofer.
Dr. Lee.
>> Thank you so much,
Dr. Miller.
That was an excellent
presentation.
Thank you.
I had two questions.
One, perhaps my main
question is really,
I'm thinking about the outcomes.
You're certainly focused
on disease prevention.
So capturing patients who
are symptomatic with COVID.
Is there the possibility to also
consider asymptomatic cases?
And you had mentioned up to
14 days post-vaccination.
But throughout the trial it may
be incredibly valuable for us
to understand whether
or not the,
your particular vaccine
candidate could also play a role
in preventing asymptomatic
transmission since we know
that is also of concern here.
So that's my first question.
And then my second
question is just really
if you could clarify.
You had mentioned, and
appreciate very much
that it's a very
Th1-directed phenotype.
And the Th2-directed
phenotype was rare.
But of those who may have,
you may have observed a
Th2-directed phenotype.
Is there any comment about
those patient characteristics
where you observed this finding?
For example, recent
pregnancy status.
>> So thank you for
those questions.
I'll talk first maybe to
the Phase 3 study design.
And I didn't really get
into so many details
about the COVE study
in the interest of time
and focusing on the data.
But I would be really
happy to come back
at a subsequent meeting and
kind of give a deep dive of all
of the various secondary
and exploratory objectives
that we will evaluate.
So what I've reviewed for you
are the co-primary efficacy
and safety objectives.
But in addition to that,
there are numerous evaluations
of secondary and
exploratory efficacy.
So in terms of the secondary
efficacy, we will look
at severe respiratory disease.
COVID-19 symptoms
according to the long list
of potential symptoms that are
available on the CDC website.
So milder disease.
And then also asymptomatic
disease.
So patients will be
monitored throughout the study
at various time points, looking
at non-spike protein
antibody titers.
So elevations in those
titers and seroconversion
in those titers representing
the development
of asymptomatic COVID infection.
And I would be really
happy to go through
and review at another point.
But we will look at
all COVID disease.
Asymptomatic COVID disease.
All caused mortality
and so forth.
So let's maybe plan to talk
about that in the future.
And then with respect
to the Th2.
So I really didn't get a
chance to show the slides.
But there was really, really
minimal Th2-directed phenotype.
And as that was in
the Phase 1 study,
these are healthy subjects.
So really isn't a lot of
clinical detail about them.
But for us it's extremely
reassuring
that the phenotype is really,
really heavily biased
towards Th1.
>> Thank you.
>> Dr. Bernstein.
>> Thanks for your very clear
and wonderful presentation.
I just had a question.
You mentioned that
all comers with regard
to SARS-CoV-2 serostatus
are included.
But baseline serology was
still being collected.
How will that baseline serology
be analyzed with your endpoints?
>> Thank you for that question.
So we will enroll all comers
and get the initial
baseline serostatus.
When it comes time to
perform the efficacy analysis,
the cases that accrue are really
based on its first time efficacy
for that primary analysis.
So to be eligible for inclusion
in the primary efficacy
analysis,
subjects should have been
baselined serostatus negative.
Nonetheless, by including some
baseline serostatus positive
subjects, we have the ability to
conduct some of the sub-analyses
and exploratory analyses
we were discussing.
Looking at the history
of the subject
who may be were baselined
serostatus positive.
Evaluating whether cases
occur in those subjects.
And this is certainly
amongst the questions
that the DSMB has
asked us to look
into as we monitor the study.
>> And what, initially,
are there,
what percentage are
seropositive?
>> Difficult to say, I
would say at the moment.
Because in the largest
population,
which is the Phase 3
COVE study, you know,
their samples are being accrued
and being tested currently.
In the Phase 1 and
Phase 2 study,
it's been relatively infrequent.
I would say at around 1 percent
or so of the study population.
>> Thank you.
>> Dr. Atmar.
>> Thank you.
And I'll add my thanks
for a clear presentation.
I actually have a
follow-up question
to Dr. Bernstein's question
about baseline serostatus.
And looks like from
the Phase 1 data,
at least by the pseudo-neu
[phonetic],
you didn't have any
seropositives.
Although by the ELISAs, which
may be cross-reactive, I guess,
with other human coronaviruses.
There were some who had
measurable antibody at baseline.
Which assay are you going to use
to determine baseline
serostatus,
is the first question?
And then just a follow-up
question
to a comment you made
during the presentation
about making the race, ethnicity
data available on the website.
I took the opportunity to
go to the website and see
that you have the enrollment
numbers through last Friday.
But I don't yet see the
race, ethnicity data.
And my question is, is
this going to appear
on this week's update?
Or did I miss something
on the website?
Thank you.
>> Yeah. Maybe I'll take
the second question first,
if that's okay.
>> Sure.
>> When I last went
to the website,
I saw the 18 percent
number and the breakdown.
So I'll need to investigate
what happened there
and why you're not
able to see it.
But the intent is really to
provide it and to update it
on a weekly basis given
the amount of scrutiny
that we're undergoing.
And maybe then to
the first question.
Which was around the
baseline serostatus
and which assay we would use.
And looking at the Phase 1 data.
So, yeah, I think there were
only one or two subjects
in the Phase 1 study that
were baseline seropositive.
And there were 120 subjects
in the trial overall.
So it's a relatively
small sample size on which
to make that assessment.
We have seen more baseline
serostatus positives
in individuals in
the Phase 2 study.
At the prevaccination time
point, we will assess those,
the binding antibody titers.
As well as the neutralization
antibody titers.
And I don't know that
we've progressed so much
into our statistical
development plan to define that.
But, I mean, presumably
positivity
with either assay would indicate
that you had been
exposed previously.
>> Thank you.
And I, a follow-up
question then is,
you may not have the data yet.
But do you know, is, are
the sera responses different
in those who have
baseline antibody?
Either from the Phase 1
or what data you may have
from the Phase 2 so far?
>> Yeah, the data from Phase
1 are extremely limited.
And the Phase 2 data
are actually currently
in their stage of accrual.
So subjects have been
given the second dose.
And now they're in
that process of waiting
for one month postvaccination
to have their immunogenicity
assessment.
So we should be able to
give a better picture
on that later in the fall.
>> Thank you.
>> Final call for any questions.
I see none, so let me
thank Dr. Miller again
for this excellent presentation.
For answering question.
We'll move on to Dr.
Kitchin from Pfizer/BioTech,
who will talk about their
COVID-19 mRNA vaccine
clinical development.
>> Thank you very much.
Can you hear me okay?
>> We can.
>> Good. Great.
Thank you very much
to the committee.
And thank you for
inviting us to present.
I work in the Pfizer
Vaccine Clinical Research
and Development Global
Organization.
And we, as many of you may
be aware, have partnered
with the German company
BioNTech on development
of a COVID-19 mRNA vaccine.
Or, in fact, a suite of COVID
RNA, CIVID-19 RNA vaccines.
We have been previously
working with them
in other infectious
disease areas.
And, therefore, [inaudible]
of the COVID-19,
SARS-CoV-2 pandemic.
The platform was ripe for
us to collaborate further.
So if you could go to
the next slide, please.
So what I've planned to
present is an overview
of our clinical development.
Both Phase 1.
And I will present some data
from our Phase 1 study or part
of our study that directed
our decision as to what
to move forward with in
larger scale development.
And then I will present
an overview
of the Phase 2-3
part of the study.
So if you look on the
right-hand side of this slide.
You'll see that we
initially started developing
in two different clinical
studies, that I'll show
on the next slide,
four different types
of RNA vaccine targeting
the SARS-CoV-2 virus.
They were encoding either just
the receptor binding domain part
of the spike antigen
or the whole spike.
Again, the P2S pre-fusion
stabilized form.
The four different candidates
based on either unmodified RNA.
Modified RNA.
Or self-amplifying RNA.
And we have focused
the attention
of our large-scale
development and what I will talk
about further moving forward
[inaudible] two modified RNA
candidates given as a
two-dose schedule separated
by three weeks.
The so called B1 candidate,
which encodes for the RBD only.
And the B2, which encodes
for the P2-mutated
[inaudible] spike protein.
Next slide, please.
So I mentioned that there are
two ongoing clinical studies
assessing the [inaudible]
tolerability.
Immunogenicity.
And ultimately moving
forward to now efficacy
of these mRNA vaccines.
The initial study in the
U.S., shown there on the left,
started off as a
Phase 1-2 study.
But it's now formally expanded
into a Phase 3 efficacy
evaluation that I will explain
in a bit more detail later
on in the presentation.
And then in Europe in Germany,
a study has been
conducted whereby all
of those four different types
of vaccine are being
evaluated in different doses.
And the importance for
that study, particularly
for this presentation and for
our decision to move forward is
that T-cells were collected
and analyzed in that study
as opposed to in the U.S. study.
So in the Phase 1 part
of the U.S. study,
we enrolled 15 healthy
participants per dose level,
of whom 12 received
the active vaccine.
And three received placebo.
And we enrolled them in
two different age groups.
Either 18 to 55.
Or 65 to 85.
These subjects were healthy.
And were prescreened for absence
of antibodies to SARS-CoV-2
or positive PCR on a nasal swab
at the time of vaccination.
We initially planned to evaluate
dose, sending dose levels of 10,
30 and 100 micrograms.
But for the 100-microgram dose
level for the B1 candidate,
we saw [inaudible] profile
that we did not think fitted
with a vaccine that was
going to be implemented
at a population level.
And we, therefore, turned our
attention to lower dose levels
in the range of 10
to 30 micrograms.
And as I said before,
that's administered
as two doses at Day
1 and Day 21.
And just to note because of
that reactogenicity finding
for the 100 microgram group,
they did not receive
a second dose.
We have also made
comparisons informally
with a human convalescent
serum panel
from 38 human convalescent sera,
you can see in the box there,
from subjects over a broad
age range of 18 to 83.
Which were collected at least
14 days after diagnosis.
Which was PCR confirmed and
once subjects were asymptomatic.
The majority, 35 of the 38,
were symptomatic infections.
And one has been hospitalized.
And if you wish to view these
data further, there are a number
of publications cited
there at the bottom.
Either formerly published,
having been peer-reviewed.
Or in prepublication
format on med archive.
You can go to the
next slide, please.
So this is an overview of the
study that's currently running
in the United States I mentioned
briefly on the previous slide.
So on the left-hand side,
I'll focus my attention
to start with.
And the right-hand side that's
grayed out, I'll come back
to later on when we talk about
the Phase 2-3 components.
So in the Phase 1 part of the
study, we enrolled 195 subjects.
As I said, 15 per group
in those two age groups
that you can see shown
there in the table
at the various different
dose levels.
And as is usual, in our
early phase vaccine studies,
we describe the safety
in a thorough [inaudible]
profile via participant-reported
outcomes elicited
by electronic diary.
Local reactions.
Systemic events,
including fever.
And also use of analgesics
or antipyretics.
As well as adverse events.
And we collect all adverse
events for one month
after the second dose.
And serious adverse
events for six months
after the second dose.
And in this early
part of the study,
we also collected
standard hematology
and biochemistry samples.
In [inaudible] immunogenicity,
we've assessed this
in a number of different ways.
Focusing our attention
on neutralizing tiers
analyzed using a true viral
neutralization assay.
As well as looking
at binding antibodies
against either the
S1 or the RBD.
However, what I'll present
here will just be the
neutralizing titers.
As we feel that those are likely
to give the best representation
of potential future
performance of the vaccines.
You can go to the
next slide, please.
So in summary, and then I'll
show you the data that's
supported this, of the
B1 versus the B2 study.
The vaccine encoding the RBD
versus the vaccine encoding
the full spike protein.
We selected the B2.
To the full length spike
encoded vaccine at the highest
of the three refined dose
levels that we looked at.
The 30 micrograms dose.
And that is our focus for
the late-stage Phase 2
and Phase 3 development.
And we used a number
of different criteria
to determine how best to
choose both the candidate
and the dose level based on,
obviously, acceptable safety
and reactogenicity of, paramount
for a vaccine potentially
for a wide-scale global use.
We were looking,
focusing our attention
from an immunogenicity
perspective, as I said,
on neutralizing titers.
And we did use the human
convalescent serum panel
as an informal reference.
And we also wanted to see a
strong Th1 type T-cell response
both for CD4 and CD8
positive T-cells.
And both candidates
looked potentially strong.
But, overall, the beta favored
the choice of the B2 candidate.
The one encoding in the
full-length spike protein.
Based upon, and I'll show
you some of these data
on the following slides.
The reactogenicity profile for
the B2 being more favorable
than the B1 in both the
young and the older adults.
A trend towards stronger CD8
T-cell responses with the B2.
And earlier clearance of
SARS-CoV-2 RNA in immunized
and subsequently
challenged [inaudible].
So based on all of these
data, it is the B2 candidate.
BNT62b2 at the 30-microgram
dose level that we're studying
in the large part of the study.
Next slide, please.
Okay, so let me show you
some reactogenicity data
from the Phase 1 part.
If you could go to
the next slide.
So, first of all,
what I'm showing here
for the B2 is the local
reactogenicity profile
in Phase 1.
So just to orientate
you, there's going
to be a couple slides with
a slightly similar layout.
So in the top part of the slide,
you have the data
after dose one.
So this is just as a reminder,
this is participant-reported
outcomes in an electronic diary
on the evening of the each
of the seven days
after vaccination.
And the data are
presented cumulatively.
Dose one in the top half
of the slide and dose two
in the bottom part of the slide.
And then on the x-axis you
can see the various symptoms
that were solicited for.
And the varied dose levels.
The 10, 20, and the
30-microgram dose levels.
And then the P standing
for placebo.
The left-hand side of each graph
shows the three local reactions
solicited for in the
younger age group.
The 18 to 55 year olds.
And on the right-hand side,
exactly the same
data presentation,
but for the older age groups.
And then each bar is a
stacked cumulative bar chart.
With the light green
showing the mild symptoms.
And I should have said earlier
that these local reactions
and systemic events were all
graded by participants according
to the FDA grading scale.
The FDA grading scale.
So the light green is for mild.
The yellow for moderate.
And then the darker
teal for severe.
But you can see that across all
three dose levels, at both doses
and in both age groups.
Pain at the injection site was
the most common local reaction.
Perhaps with an indication, at
least in the younger age group,
of very minor, small numbers,
of course, increasing with dose.
But less common in
the older subjects
than in the younger subjects.
And you will see that
redness and swelling,
whilst pain is a
predominant symptom, redness
and swelling were
relatively uncommon.
You can go to the next slide.
So let's turn from
local reactogenicity
to systemic reactogenicity.
So, again, we've got
a similar layout here.
But now because we solicit
for more systemic events
than we do local reactions.
What I'm showing on this
slide is, first of all,
is the younger age group.
The 18 to 55 year olds.
But, again, dose one
on the top panel.
And dose two on the
bottom panel.
Again, this is for, this is
just for the B2 candidate.
So you can see that
particularly,
if we focus our attention on
the more objective symptoms.
So particularly fever,
for example.
You can see that in
the younger age group,
after dose one there was just
two subjects reported fever.
One mild and one
moderate after dose one.
And three after dose two.
One in the 20-microgram
group and two
in the 30-microgram group.
In terms of chills, again,
that's more objective
than things like
fatigue and headache.
And that's what's born out
hen you look at the rates
in the placebo group
compared also
to the active vaccine groups.
You can see, again, it does
appear to be an increase
in frequency with
increasing dose.
But, again, very tolerable.
These reactions tend to
occur on either day one
or day two after vaccination.
And are short lived, resolving
within one to two days.
That's for the younger age
group, the 18 to 55 year olds.
And if you go to the second,
the next slide, I'm sorry.
This is exactly the same
layout for the older age group.
The 65 to 85 year olds.
And I think you perhaps saw,
when the slide transitioned
there, that the overall height
of the bars on this
graph appear lower
than on the previous graph.
Indicating better tolerability
profile amongst the older
subjects compared to
the younger subjects.
And, in particular, if you
look at fever, for example,
in all of the dose levels there
was only a single reported fever
in one subject in the
30-microgram dose group.
Mild, so 38 to 38.5
degrees Centigrade
after the second dose.
I've not presented
the B1 data here.
But this did show,
these tolerability data were
preferential compared to,
the B2 data were
preferential compared to the B1.
And that was one
of the key factors
that helped us choose B2
encoding the full spike
over the B1 encoding
the RBD only.
If you could go to
the next slide.
The other thing to say
is that there were no,
in the Phase 1 part of the study
there were no serious adverse
events reported by any subjects.
In terms of immunogenicity,
I've got one graph
to show on immunogenicity.
And, again, let me orientate.
You it's quite busy.
So here the majority of the dose
of the B2 in the teal colors.
But I also included the B1
30-microgram dose level just
as a comparison and
as a reference.
So what you can see is the 18
to 55 year old age
groups on the left.
And the 65 to 85 on the right.
These are 50 percent
serum neutralizing titers
in a true viral neutralization
assay.
The placebo subjects
are grouped together
on the left in the gray.
Then each of the
available time points
for the various dose levels
are shown along the x-axis.
So vaccinations given
three weeks apart.
So at zero and day 21.
And then the seven day post-dose
two sample taken at day 28.
On the extreme right-hand
side are the results
from the human convalescent
serum panel
that I referred to earlier.
The height of the bars
and the numbers shown
above them represent the
geometric mean titer.
And each individual point
is an individual subject.
And these data, these are all
available immunogenicity data.
And I'll explain why
that's notable in a moment.
So what I think you can see
is that comparing the 10
with the 20 and the
30-microgram dose levels
in the younger subjects,
there is an increase
in the geometric mean titer
after the second dose.
Particularly at day 28.
We do see some binding
antibody at day 21.
But the neutralizing
antibody really picks
up after the boost
with the second dose.
And just to point out,
my comment about these being all
available immunogenicity data
for the 30-microgram dose level
that we actually selected.
You will see, if
you've got eagle eyes,
that for the day 28 there is a
teal triangle right down there
on the baseline of the axis.
That was, in fact, a subject
who had their blood sample taken
after the protocol window.
That was only two days
after the second dose.
So when that subject
is excluded,
the geometric mean titer is
at a similar level to seen
after the 20 microgram.
And you can see, if you compare
the 30-microgram dose levels
at the B2 and the B1 show
rather similar levels
of neutralizing antibody titers.
And, again, so, therefore, our
selection of the B2 on the basis
of similar immunogenicity
but better reactogenicity
is what drove that.
The other thing also
notable on the slide is
if you compare the younger age
group to the older age group
for the same dose level.
Both for the B1 and the B2.
You can see that the
geometric mean titer are lower
in the older subjects than
in the younger subjects,
as might be expected.
However, what's key is that, if
you compare in all of the groups
after they've received
the second dose,
you can see that the GMTs
are significantly higher
than that observed in the
human convalescent serum panel.
Of course, it's difficult
to know at this point
in time what the true meaning
of the human convalescent serum
and neutralizing titers are.
However, I think they represent
the best benchmark that we have
at this point in time.
And to help guide our
selection as to what to take
into further development.
If you go to the
next slide, please.
Finally, in terms
of immunogenicity,
we did not collect
T-cells in the U.S. study.
But we did collect T-cells
in the German study.
I've just got one
slide to show on those,
if you can go to the next one.
What we see is, I just
want to make clear,
this is for the B1 candidate.
The B, the data for the B2
are still under preparation.
However, what I can say is
that the data from B2 look
at least as good as the B1.
And show a similar pattern
in terms of inducing strong,
both CD4 and CD8
positive T-cell responses.
Again, with a Th1 dominant.
So if you look there,
you can see the increase
between the pre and the post.
So that the pre is
before the first dose.
The post is on day 29.
So a week after the second
dose, you can see nice rises
in serum gamma and IL2.
And very little response
for IL4.
Next slide, please.
You go to the next slide.
Thank you.
So our Phase 1 data gave
us encouragement that,
from both safety and a
immunogenicity perspective,
advancing BNT162b2 encoding the
full length spike antigen looked
like a good candidate from a
reactogenicity perspective.
Where the reactogenicity
we observed was lower
after the first vaccination
compared to the second was lower
in younger than older
participants.
Or lower in older participants.
I actually got it the wrong
way around, apologies.
And the profile appears
at least as good
as approved adult vaccines.
And, therefore, should
be supportive
of a widespread immunization
program.
In terms of immunogenicity,
we saw strong neutralizing
antibody responses
from seven days after
the second dose.
We are still collecting data.
These subjects will be enrolled,
will be included for two years
after their second dose.
And we are still
collecting and analyzing data
from time points
beyond that obviously.
But we don't have those
data yet available to share.
And, finally, we saw, again, I
think important, both strong CD4
and CD8 sera responses
with a Th1 dominance.
So we, if you go
to the next slide.
We, therefore, elected to
take the BNT162b2 candidate
into Phase 2-3 development.
And then the next slide at
the 30-microgram dose level.
So if we now focused
on the right-hand side
for this part of the study.
We have, so the Phase 2
component represents the first
360 subjects enrolled in the
overall larger Phase 2-3.
So 180 per age group
and per vaccine.
So they are randomized
one to one.
Unlike the first
part of the study
where the randomization
was four to one.
In this part of study
where our primary endpoint
for the Phase 3 part is
efficacy, we are randomizing one
to one active to the placebo.
Aiming to enroll
an overall target
of approximately
30,000 subjects.
And you can see the
age split there.
So we're targeting approximately
60 percent of the subjects to be
in the 18 to 55 year
old age group.
And about approximately
40 percent to be in the 56
to 85 year old age groups.
The primary objectives in
this part of the study are
for the Phase 2 part to define,
further define the safety
profile and the immune responses
to the BNT162b2 in those first
360 Phase 2 participants.
And then for the
large Phase 3 portion,
the efficacy objective is
to evaluate the efficacy
of the vaccine against
confirmed COVID-19.
Firstly, in those
without evidence
of infection before vaccination.
So we take a baseline serum
sample, which we evaluate
for a non-vaccine antigen.
And nasal swabs for presence
of SARS-CoV-2 by PCR.
Again, we don't exclude
subjects based
on either of those parameters.
They are included.
But for the first part of
this primary objective,
they would be not
included in the analysis.
Because the first part is
only in those without evidence
of infection before vaccination.
And then the second
part of the objective is
to include all comers, both
those with and without evidence.
And, again, that's important
when considering implementing
a vaccination program
at a population level.
Where clearly there will be
vaccinees who will be naive.
But also those who have
been previously exposed,
either knowingly or unknowingly.
Of course, the safety
profile is paramount
for this type of vaccine.
Again, we will be
assessing local
and systemic reactogenicity
by electronic diary
in the subset of participants.
And adverse events
in a similar way
to the Phase 1 part
of the studies.
Including all adverse events
up to one month after
the last dose.
And serious adverse events up to
six months after the last dose.
And we do have additional
secondary
and exploratory objectives
to look at severe disease,
looking at, using the
broader CDC case definition.
And looking at SARS-CoV-2
infection.
Next slide, please.
So in a simple schematic
in terms
of how we surveil for efficacy.
So this study started
on the 27th of July.
I'm pleased to report that
the enrollment is already more
than 50 percent accrued.
So subjects will receive
two doses of vaccine
in the same ways in the Phase 1
part, separated by three weeks.
And as well as capturing
reactogenicity
and adverse events, we will be
doing intensive surveillance
for potential COVID-19.
And if a subject
experiences a symptom
that could potentially
represent COVID-19,
they are to contact their
investigational site.
And that triggers
either telehealth
or an in-person visit.
And a nasal swab.
And then we will be defining
our cases based upon both the
presence of one or
more symptoms.
As well as a positive
SARS-CoV-2 PCR positive.
And as I said before, we'll be
looking at efficacy both in,
first all of, in those
without evidence of infection.
And then next in the
total population.
We plan to follow subjects
for up to two years
after the second dose with
regular follow-up visits.
We, too, are focused on
enrolling a diverse population.
What I should, do what I
should have said also is
that this is an international
study.
Including the United States.
Latin America.
Europe. And South Africa.
The majority of subjects will
come from the United States.
Our current enrollment shows
that we have approximately 19
percent of subjects enrolled,
either black or Hispanic.
And 4 percent Asian.
And we are also working
with sites
to enroll Native Americans also.
And, obviously, in Latin America
and in the other regions,
there will be increased
diversity also.
And with that, I think
that is my final slide.
If you go to the next one.
I'm now going to hand
over to, I'll be happy
to take questions afterwards.
And have other colleagues
on the line
who can also answer
questions if you have them.
But I'm now going to hand
over to Brian Gleason
from our global suppliers
to talk about the storage
and handling of the vaccine.
>> Good morning, good afternoon.
Thank you.
Bryan Gleason.
I'm here representing Pfizer
Global Manufacturing Supply.
And I am the Pfizer launchee
[phonetic] for the vaccine.
So I'd like to thank ACIP
for the opportunity
to present today.
Next slide, please.
So the first slide I'd like
to five you an overview
of the product packaging
for supply, for the vaccine.
The first primary
packaging on the left side
of the slide is going
to be filled,
is probably [inaudible] filled
into 2-mil, type-1 glass,
preservative free,
multi-dose vials.
Each multi-dose vial
has five doses.
And each multi-dose vial
has 0.45 milliliters
of frozen liquid or product with
point of use dilution required.
Second step along is
the secondary packaging.
And that would be a
single pack into a tray.
Each tray will have
185 2-mil vial.
Which gives us a total
of 975 doses based
on the 5 dose NTP [phonetic].
Each tray is approximately, in
inches, about 10 inches square.
Or, you know, 230
millimeters square.
After secondary packaging, if
it passes on to thermal shipping
into a tertiary container.
And here we have designed an
innovative [inaudible] solution
to ensure [inaudible]
and tracking
of our required cold-chain
conditions.
Each time the shipper will
utilize real-time temperature
monitoring devices.
Including GPS tracking
and technology to allow
for 24/7 in-transit control.
And have security and also
allow for any mitigating actions
on temperature deviations,
if required.
Each shipper can take up to
one tray up to five trays.
So you can fit one
or up to five.
So one, two, three, four or five
trays into a thermal shipper.
It will be submerged in dry
ice and packed up for shipping.
The total [inaudible] weight
is approximately 35 KGs
or 70 pounds.
Next slide, please.
Okay, so when the thermal
shipper arrives at the point
of vaccination, there
are a number of options.
On the left side, first option
is to remove the vaccine tray
or trays from the
thermal shipper.
And store in a [inaudible]
temperature freezer
at minus 70 plus minus 10 C.
Where it can be stored
frozen up to six months.
And there are many
different sizes and designs
of ULT freezers available.
And smaller under-bench type
pharma-grade freezers can hold
typically up to about
30,000 doses.
And the more familiar
larger operate designers,
design freezers can store
well over 200,000 doses.
So [inaudible] freezers would
be there in the marketplace.
Long-term stability studies
will continue under protocol
to inform drug product
shelf life at minus 70.
[inaudible] in the
middle of the slide.
You can utilize the thermal
shipper for extended storage.
Each shipper is validated to
keep the vaccine payload as,
optimal temperatures
for up to ten days.
And on receipt at the
vaccination center,
after opening, we recommend
that the thermal shipper should
be replenished with dry ice.
So the dry ice replenishment
needed within 24 hours.
Thermal shipper can be
replaced every five days.
And you can extend the
storage every five days
when replenishment [inaudible]
keep it for an extended period.
If there's difficulty sourcing
dry ice, services locally.
Pfizer has strategic suppliers.
And we have a reference list
which we'll share, of course.
The recommendation for
the thermal shipper is not
to open more twice per day.
Probably to elongate
the cold storage.
And after opening
also recommends
to close within one minute.
On the right side production
is to remove the vaccine
from the thermal shipper and
put it into a refrigerator at 2
to 8 degree C. And where, based
on current stability data,
it can be stored
for up to 24 hours.
We have ongoing to stability
studies which will continue
to characterize our
drug quality stability.
And over time the
expectation is the new date
from these study will help
to optimize and/or allow those
storage temperatures to update.
Post dilution and in-use
period is expected at six hours
at 30 degrees C. Okay,
that's the last slide.
Thank you for your time.
>> Very good.
Thank you both for
those presentations.
Dr. Cohn wanted to say
a couple of words first.
And then we'll open
up to questions.
>> Thank you so much for all
of that really important
information that you just shared
for both products on
vaccine storage and handling.
I just want to let all
of the listeners know
to not start going online right
now and purchasing freezers.
We are working on solutions
through our distribution
and administration planning
for these very complex storage
and handling requirements
at this time.
Additionally, I think hopefully
Pfizer can comment on sort
of a timeline on additional
studies on stability
that may shift these plans.
But we just, I want to
let everyone know that,
as soon as we're able, we
will start sharing information
about how CDC and HHS through
operation warp speed are going
to be supporting programs
at maintaining this
vaccine at this temperature.
Over.
>> Thank you Dr. Cohn.
So I will take chair's
prerogative
and ask first couple
of questions.
First of all, the timing
of your signs and symptoms
for adverse reactions.
Do you have a window for that?
Because that's going
to cause some problems
because they mimic signs
and symptoms of COVID.
And may lead to excessive COVID
testing in this population.
And, second, and
vaccines, excuse me.
And the, second of all,
what are your plans
for measuring antibody
persistence over time?
>> Thank you very
much for the question.
So we did provide some
guidance to our investigators
about recording potential
COVID symptoms
in the first seven days
after vaccinations.
[inaudible] there is a
potential overlap between some
of the more common symptoms
and the reactogenicity.
So the we don't anticipate an
over-testing for COVID during
that period based
upon that guidance.
In terms of persistence
of immunogenicity.
So the studies currently plan
to follow subjects for up
to 24 months after
they've been vaccinated.
And we will have leads
across that whole period.
So we will have,
at least for now,
those NLCBs [phonetic]
are going to be the first,
these are the first
subjects vaccinated
in hopefully what will
be an ongoing program.
>> Thank you.
Dr. Lee, please.
>> Thank you very much.
Two questions.
First is, and actually this
applies perhaps for all
of the trials we'll be seeing.
You know, are there ways for us
to capture the full
benefits of vaccination?
So I recognize that
respiratory disease or some
of the systemic symptoms
that are prevented are sort
of classic COVID presentations.
With regard to the potential
to capture other disease
manifestations secondary
to COVID infection.
And particularly as we in
the future get to trials
in children, I think
it might be helpful
to widen and capture that.
Perhaps it's in your
secondary outcomes.
And, again, I'll emphasize
that asymptomatic infection
and thinking more about
the response earlier
from capturing via
PCR versus serology.
I actually feel like
with serology
and asymptomatic infection,
we sometimes are not seeing
as strong a response as we are
with symptomatic infection.
And also in order to really
think about herd immunity
in the way that we
would like to.
Such as, you know, comparing
polysaccharide vaccine
to conjugate vaccine in kids.
And the differential impact
it has on the population.
It would be extremely
helpful for us
to understand the
potential for each
of the vaccine candidates
to have that impact.
And I have one more question,
but I'll pause there
for a second.
>> Thank you.
So I think, yeah,
so I'm just trying
to assemble what you said.
I think a number of those things
that you've mentioned are
probably going to have
to be studied in
further studies.
And, in fact, you know, perhaps
even in following implement,
you know, assuming efficacy
and safety are demonstrated
in implementation studies.
For example, you know,
looking at herd immunity
and that type of thing.
For our part we have
tried to keep, you know,
bearing in mind the
number of subjects needed
to be enrolled in the study.
And the, you know, the urgency.
We have tried to keep the
study as pragmatic as possible
in the first instance.
Rather than overloading it with
a lot of additional procedures
that might make the
implementation
of the study difficult.
But I think those are
things that we can come back
to look at in future studies.
The other thing to
say is that we are,
you mentioned pediatrics there.
We are also, we're in
dialogue with regulators,
both in the U.S. obviously.
And also elsewhere
about [inaudible] some
pediatric studies that we,
as well as studies
in pregnant women.
And in other potential groups
that we would be looking
to implement as early as we can.
>> Thank you, Dr. Kitchin.
One more question.
I just wanted to clarify.
So with regard to
the safety follow-up
in the Phase 3 studies.
I saw on one slide that for
severe adverse events it's
potentially up to six months.
And also on another slide
that you're following patients
out to two years with regard
to, you know, efficacy and,
you know, postvaccination
infection.
Is it also possible
to clarify whether
or not you'll extend safety
monitoring out to two years,
at least for the
serious adverse events?
>> So, yes.
You're right that
it's surveillance
for serious rather than severe.
Serious adverse events
which ended
up being an important
distinction up to six months
after the second dose.
That doesn't, that's if you
like the active surveillance.
It doesn't preclude reporting
adverse events beyond that.
And we have some experience
of long-term follow-up
vaccine studies
where investigators continue
to report adverse events
during that period.
So that's the current
plan for reporting
of all serious adverse events.
I think beyond that would
then depend upon, you know,
if any adverse events
of interest
or signals were observed
that we needed to focus
on additional safety
surveillance beyond that.
But investigators are at
liberty to report adverse events
at any time during the trial.
>> Thank you.
And maybe just another comment.
Not, specific for, perhaps
for all trails for us
to consider standardizing them,
safety monitoring
postvaccination
in the Phase 3 study.
Just because I think, you know,
each of the vaccine
candidates may potentially have
unique profiles.
But also just thinking about
as we're assembling the data
for vaccine safety and
reviewing it at ACIP.
It's, I think it would
be helpful for us
to have a standard
approach to that.
Again, not directed,
you know, solely at you.
But just as a general statement.
Thank you.
>> You're welcome.
>> Dr. Szilagyi.
>> Yeah, thank you very
much for your presentation.
I did have one question
about pediatric populations,
which you addressed.
The other one, for some
reason I'm unclear about this.
Are the 18 to 85 year
olds healthy individuals.
Because I know some centers are
enrolling healthy individuals.
And what is the
representativeness in terms
of underlying high-risk
conditions?
>> Yes, thank you
for the question.
And I should have
maybe said more
about the inclusion criteria.
So the, in terms of
underlying illness,
we are including healthy
population between the age,
currently between the
ages of 18 and 85.
But are also in dialogue
to potentially extending
that range.
But when we say healthy,
that permits subjects with
or potential participants with.
[ Audio Error ]
Sorry. My telephone.
I don't know if you
could hear that.
My telephone started
ringing on the same speaker
as I was trying to speak.
Sorry. That's put
me off slightly.
What was I saying?
Yes, so healthy participants
can include subjects
with chronic medical
conditions provided they are
considered stable.
And we define stable as
meaning no change in therapy
or significant intervention
within the past six weeks.
So we do already have
significant numbers of,
and that's the same
across all sites.
Just to be clear, I'm not
sure if you were suggesting
that some sites are
recruiting different types
of subjects than others.
The, those criteria
in our study apply
across all of the locations.
So we already can see from the
baseline medical history data
that we've started to accrue
that there are significant
numbers of people
with underlying medical
conditions.
And as we accrue more, we'll be
able to better represent what
that population looks like.
But our intention, obviously,
within the constraints
of a Phase 3 efficacy study are
to recruit a population that is
as representative in
all ways as possible.
>> Okay, that's helpful.
Specifically I was thinking
ab out hypertension.
Diabetes. Obesity.
Chronic lung diseases
that are included.
[ Multiple Speakers ]
>> Certainly hypertension
and obesity and diabetes are
at the top of the list of,
we've got significant numbers
of subjects with those
conditions already enrolled.
>> Thank you.
>> Dr. Poehling.
>> Hi, Kathy Poehling.
Dr. Kitchin, thank you for
this great presentation.
I wanted to ask for
clarification.
I saw that on your
Phase 1 and 2,
you said there was a
predominance of Th1 response.
And you showed data really
for the B1 in we're going
to be moving forth with the B2.
Could you share what we've seen
about, with the Th2 response?
And then second is,
would you clarify
if in the Phase 3 study
the Th response is going
to be included?
Aligning to what Dr.
Lee had talked about,
making sure we're comparing
more things across studies.
>> Yeah, so the operational
complexity of collecting samples
for T-cell analysis
is quite substantial.
So typically we will
only collect those
in relatively small,
very controlled settings.
So in this large Phase 3 study
that we're now conducting,
we do not plan to
collect T-cell samples.
However, I think the nature
of those analyses means
that the analyses that
we're able to perform
in the early Phase 1 studies
give a good representation
of what the T-cell
responses would look like.
The, in terms of the, so
I did present those data
for the B1 candidate only
so I, what I didn't say
in the presentation
was that the subjects
that received the B1 were
in fact the first ones
enrolled into our study.
So, therefore, the basis for
them comes available sooner
than the B2 who we
recruited a few weeks later.
So for the B2 data,
what I can say is
that at this stage the
preliminary data looks at least
as good as for the B1.
And we hope to be publishing
that in very short
order probably
within the next week or so.
At least on a preprint server.
>> Ms. Bahta.
>> Yes, thank you.
This has been great to
hear these presentations.
In the slide where you talk
about the efficacy schema,
which has now just starred.
In the discussion for active
surveillance, you're saying
that you're either
going to do telehealth
or in-person visit
and nasal swab.
What's the criteria?
Like what, why aren't
you doing nasal swab
for symptomatics in
all the subjects?
Or maybe can you just explain
that a little bit further?
>> Yeah, sure.
Yeah, and the short
answer is, yes, we are.
Maybe I wasn't clear enough.
So the way that it
works is that,
if somebody experiences one
of the trigger symptoms,
which are the, you know,
the typically recognized
symptoms for COVID-19.
They are advised to contact
their investigational site
by telephone in the
first instance.
And if it is confirmed that
they do indeed have one
of those symptoms, they are
asked to either, so they,
when they're first enrolled,
they're given a swab kit
to take away with them.
Then depending upon
their circumstances,
the country in which
they are enrolled
and the site circumstances.
They can either perform
a self-nasal swab
and ship that directly to us.
Or they can attend the site
and have an in-person visit.
And have the swab
performed there.
But either way, anybody
that has confirmed,
and when I say confirmed,
I mean by the investigational
site staff, a confirmed symptom
that could represent COVID-19.
They are all intended to
have a swab performed.
If that clarifies.
>> Dr. Fryhofer.
>> Sandra Fryhofer,
American Medical Association.
On your Phase 2-3
efficacy schema,
which started on
July 27th, 2020.
You said that you are
collecting diversity information
on the participants.
And right now 19 percent
are black or Hispanic.
And 4 percent are Asian.
Obviously, from all the
questions you've heard,
this is very important
to so many people.
We have a population to cover.
This is important
not only to trust.
But with so many
different vaccines that are
under investigation with
possibly different profiles.
This sort of diversity
information
on the participants
would be so helpful.
Are there any plans to include
that information
specifically on your website?
>> So I don't know
the answer to that.
I don't know if one of my
colleagues on the line is able
to speak to that more.
What I can tell you is that, you
know, we are, it is, like you,
it is something that
we're very cognizant of.
And, you know, particularly
with the, you know,
the pattern of COVID and how
it disproportionally affects
minority groups.
You know, that's something
we are actively seeking
with working with our
partner sites to put in place,
tools to help with outreach
into the population.
To try and, because,
as was said earlier,
it's not straightforward
to enroll minority groups
in large numbers into
clinical tries in general.
And, you know, I think we've
made good headway so far.
But are always seeking
to do better.
>> Dr. Kimberlin.
>> Another of the
characteristics
of this disease is inflammation
throughout the body.
Are you all measuring
any measures
or markers of inflammation?
Even something as crude
as SED rate or CRP?
>> We are not measuring
those in our study, no.
We do capture, you know, if
parameters are kept as far
as someone's medical care.
Those sorts of parameters
we will capture those.
But we don't have them performed
under the study protocol.
>> Dr. Fryhofer, do you
have additional questions?
>> Yes. Sandra Fryhofer, AMA.
One more question.
You indicated on your
slide showing on Phase 1,
showing reactogenicity,
that there was an
error on your slide.
That there was actually
less reactogenicity in older
versus younger participants.
Does this in any way
make you concerned
that perhaps the vaccine may not
work as well in older adults?
And, you know.
Maybe there's something
you've missed?
But that was an error on
your slide; is that correct?
>> Yeah. You'll see from
the graphs that I showed
that the reactogenicity is
lower in the older subjects
than in the younger subjects.
And I also showed that the
neutralizing antibody titers
were lower in the older
than the younger subjects.
But were at least as high as
the human convalescent sera.
So, ultimately, the
efficacy within the study
as a whole will be how we
can assess the vaccine's
effect overall.
And in different parts
of the population.
But until we have those data,
then we can't really
speculate about that.
>> Dr. Cohn, question?
>> Thanks.
Can you please go into
a little bit more detail
about the breakdown of
the age groups in terms
of the younger population
and the older population
in the immunogenicity
data and safety data
from the Phase 1 trial?
And also specifically
in the older group,
what is the proportion of
patients over 70 versus between,
I think it was 56 and 70?
>> Was that question to Pfizer?
So just to be clear.
So we enrolled two age,
in the Phase 1 we
enrolled two age groups.
So one was 18 to 55.
And then the other was 65 to 85.
So in the Phase 1 part, we
didn't, sorry, there's a.
>> Apologies.
I think I meant for
the 65 to 85 what?
>> Right.
>> How many?
It was not clear what
the ends were for each
of those two different groups
from the total number
of enrolled.
And what the range was
within the older age group.
Not the range, but the
proportion of patients
on the older end of that.
>> Right. So the,
just to be clear.
Yeah, so each group
that received the active
vaccine comprised 12 subjects
at each dose level.
I don't have the
exact, so bear in mind,
that's a relatively small
number in terms of looking
at the overall distribution.
But we did have representation
across that whole age
range from 65 through 85.
>> We have a question
from Dr. Maldonado.
>> Yeah, sorry.
I couldn't raise my hand.
Thank you for this presentation.
So I understood from
the previous speaker
that they weren't going
to be collecting
samples for genotyping.
But it seems to me that, if you
have a breakthrough infection
or an infection, symptoms,
and you're collecting swabs.
Would you be planning
on collecting,
since you're collecting
swabs, wouldn't you want
to genotype those to see what
the sequences look like compared
to the circulating strain?
>> So we don't currently
plan to do that.
We currently plan to use
those swabs to assess
by PCR whether there's presence
of SARS-CoV-2 genomes or not.
That's certainly
something we could think
about looking at in the future.
>> Dr. Poehling, I
still see your hand up.
Did you have another question?
>> Yes, I wanted to
follow-up really quickly.
And if I understood
correctly, the B2, Th1,
Th2 data is being put
together for publication soon.
And I wanted to ask if there
were any characteristics or,
in those that developed
a P2 Th2 response?
>> Dr. Gruber, is that something
you're able to talk to?
>> Yes. Hi, this is Bill Gruber.
I head vaccine clinical
research and development.
I, make sure I understand
the question.
Could you state the
question again, please?
>> Yes. Hi, Bill.
Kathy Poehling.
So the question is that, when
you're looking at the Th1,
Th2 responses with
the B2 vaccine.
Were there any, we understand
there's a predominance
of Th1 response.
Of those that had
a Th2 response,
were there any characteristics
that came to light?
>> Yeah, I would say, again,
that the shift was so dramatic
in terms of Th1, there
actually was very little to sort
of discern where you got
actually, for instance.
IL4 response.
So I would say there was nothing
distinguishing in that group
as Nick has indicated.
We continue to look at that data
and are preparing
it for publication.
I will say, and we commented
on this in a press release.
And I think the data
forthcoming will be available
for people to review.
As you know, the very nature
of the platform lends
itself to a Th1 response.
And that's part of the reason
it was attractive to begin with.
I think the data
is supporting that.
And, in fact, by virtue of
having the larger antigen
to be able to, or set
of antigens to be able
to stimulate immune response
by using the full length spike
protein, we have the potential.
And I think are beginning to
see some data to suggest that,
in fact, there is a
greater repertoire
of CD4 and CD8 response.
Because you've got more
[inaudible] to respond to.
Wasn't clear, obviously, from
the very start where most
of the attention
would be directed.
And that was part of
the reason for looking
at receptor binding
domain versus looking
at the full length construct.
But we're seeing, for
instance, CMI responses
against the full length.
Both the upper end of the
peptide, the N-terminal end
as well as the carboxy terminal
end when we separate it out.
And, again, that data
will be forthcoming.
But I would say that the
response is so robust,
there doesn't seem anything
to dissect out in terms
of a Th2 response because
there's so little there.
>> Thank you.
We'll take two more questions.
First from Dr. Quach and
then from Dr. Messonnier.
Dr. Quach.
>> Yes, thank you very much.
I was just wondering, given
the decreased sensitivity
of the nasal swab compared
to the NP swab, are you,
how are you going to handle
these differences between people
who are coming in to get
swabs at the vaccine center
versus those that were going
to do self-swabs at home?
>> So just to be clear,
the same swab is used
for either procedure.
So it's a nasal swabbed as
opposed to an NP swab for base.
Just whether it's the subject
that performs it themselves
or whether the site
staff perform it.
>> And so you're
not worried at all
about the decreased sensitivity
of the test compared to the NP?
>> I mean, I think
from some of the data
that I've seen it's the amount
of virus that is present
when people have true
symptoms caused by COVID.
I, that's not something I'm
overly concerned about, no.
>> Okay, thank you.
>> Dr. Messonnier.
>> Yeah, thank you.
I want to start by
thanking Pfizer and Moderna.
And all of our pharmaceutical
company partners for their work
to try to rapidly
develop these vaccines
and fulfill a clear
public health crisis need.
And I understand that, you know,
our need to move quickly
sometimes means that we have
to deal with the
realities of imperfections.
So in that context, you
know, I do want to ask,
as I'm sure Pfizer realizes,
that the complexities
of this plan for vaccine storage
and handling will have
major impact in our ability
to efficiently deliver
the vaccine.
So in that context, could you
provide anymore detail as to
when you will have more
information about storage
and handling conditions
that are less stringent?
And when you will
have more information
about the possibility
of shipping it in less,
in boxes that are less,
that have less quantity?
In other words, smaller boxes
which would also provide more
flexibility and implementation.
Thank you.
>> Yeah, thank you
for the question.
Bryan, are you still on?
>> Yes.
>> Yes, thank you.
>> I'll take the last one first.
So as we said, for
the pandemic supply,
the current minimum
shipment quantity is the 195
[inaudible] box.
And we're investigating
the viability of a less
than a 195 count
[inaudible] or smaller box.
We're not able to confirm
at this time whether that's,
what the feasible date
for that would be.
But we're currently
looking into that.
So, again, it's something
we can come back to you on.
>> All right, thank you
very much, Dr. Kitchin.
And thank your colleagues
for the presentation
and answering the questions.
For all, we are now
going to go to lunch.
Because we want to stay
on time, and you're all
on different time zones.
We will meet again in 20
minutes at half past the hour.
Thank you all very much.
