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BioNTech SE
Confidential Interim Clinical Study Report - BNT162 -01
Synopsis Page 1 of 20
Version: 3.0
Date: 20 MAR 2021
2 SYNOPSIS
Title of study A multi -site, Phase I/II, 2 -part, dose -escalation trial investigating the safety and
immunogenicity of four prophylactic SARS -CoV-2 RNA vaccines against COVID -19
using different dosing regimens in healthy and immunocompromised adults
Study number BNT162 -01
Protocol version Version 9.0 (dated 05 OCT 2020); the version valid at the 23 OCT 2020
reactogenicity, safety, disposition, and immunogenicity data cut-off
Type of report Interim report (the BNT162 -01 study is clinically ongoing; see the below notes)
This clinical study is still clinically ongoing. This third interim clinical study report (CSR) summarizes reactogenicity and
safety data available for BNT162b1 and BNT162b2 collected up until Visit 8 (the first follow -up visit at ~63 d after the
second dose) for dose -escalation and dose -expansion cohorts (dose groups) in Part A of this study, therefore this CSR
only describ es the study conduct relevant for these dose groups. This CSR differs from the second interim CSR in that
additional cell -mediated immunity (CMI) data were added for a small number of participan ts that received 10, 20, and
30 µg BNT162b2 using research s amples collected at Visit 8 (63 d post -Dose 2) and Visit 9 (162 d post -Dose 2) .
The respective data cut -off dates are: reactogenicity, safety, disposition, and immunogenicity data ( 23 OCT 2020); T -
cell response data (ELISpot data) data (02 MAR 2021); intracellular cytok ine staining (ICS) data (17 NOV 2020 for
BNT162b1 and 02 MAR 2021 for BNT162b2).
The data reported here, together with data from other sources including the study B NT162 -02/C4591001 , were used to
select the BNT162 vaccine and dose level for further study in the Phase II/III evaluation of efficacy.
Data not included here will be provided in later interim reports and/or the final CSR, which will include data for the other
IMPs under investigation in this study (i.e., BNT162a1 and BNT162c2).
Regulatory
identifiers EudraCT no.: 2020 -001038-36; ClinicalTrials.gov: NCT 04380701; WHO UTN:
U1111 -1249 -4220
IMPs BNT162: SARS -CoV-2 - RNA lipid nanoparticle (RNA -LNP) vaccines utilizing
different RNA formats, i.e., BNT162b1 and BNT162b2
Phase of
development I/II
Study sponsor BioNTech SE, 55131 Mainz, Germany
Coordinating
investigator Dr. Dr. med. Armin Schultz, CRS Clinical Research Services Mannheim GmbH,
Germany
Study sites Sites in Berlin and Mannheim, Germany
Study period Study start / end date: 23 APR 2020 / Ongoing
Study design
This is a multi -site, Phase I/II, 2-part, dose -escalation and dose -expansion study.
The study includes the first in human dose and dose ranging groups in hea lthy young er
participant s (aged 18 to 55 years [ yrs]) and older participant s (aged 56 to 85 yrs). For a summary
of this study as a flow diagram, see Figure 1.
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Dose groups 1 to 7 with younger participants (aged 18 to 55 yrs)
Dose groups 8 to 10 with older participants (aged 56 to 85 yrs)
Figure 1: Dose group schema for BNT162b1 and B NT162b2 ( Dose 1 and Dose 2, ~21 d apart) c
a) The data assessed by the SRC for progressing comprises 48 h data for six participant s.
b) Subjects will be dosed using a sentinel dosing/subject (2 -4-6) staggering process unless the planned d ose is the same or lower than
previously found to show acceptable tolerability (in which case, all subjects may be dosed on one day).
c) For the dose regimens, see the synopsis section “ Study treatments ”.
d = day(s); FIH = first in humans; SRC = Safety Review Committee; subject = participant.
Note: This report only presents data and background nformation relevant for the reported Dose Groups 1 to 10.
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Study treatments
Name: BNT162 vaccines - Antiviral RNA vaccines for active immunization against COVID -19.
IMP and dose
levels: Younger participants aged 18 to 55 yrs:
BNT162b1: 1 µg, 3 µg, 10 µg, 20 µg, 30 µg, 50 µg, and 60 µg.
BNT162b2: 1 µg, 3 µg, 10 µg, 20 µg, 30 µg.
Older participants aged 56 to 85 yrs:
BNT162b1: 10 µg, 20 µg, and 30 µg.
BNT162b2: 10 µg, 20 µg, and 30 µg.
Dosing
regimen : Two injections ~21 d apart. Injection volumes were up to 0.5 mL. Use of the same arm
for both doses was allowed. The non -dominant arm was preferred.
Dosing route: Intramuscular (IM); upper arm, musculus deltoideus.
Batch Nr. BNT162b1: E220195 -0001L, E220195 -0004L, E220195 -0014L .
BNT162b2: E220195 -0004L, E220195 -0017L, E220195 -0018L .
This was an open -label study. There was no randomization to treatment groups.
Study population
Healthy younger participants aged 18 to 55 yrs (Dose Groups 1 to 7) and healthy older participants
aged 56 to 85 yrs (Dose Groups 8 to 10). There were no protocol waivers or exemptions to the
defined inclusion/exclusion criteria.
Methodology
Study participants were selected based on their reported background and the outcomes of
assessments performed at up to 30 d before Day 1. Study participants meeting all
inclusion/exclusion criteria were allocated to study treatment and dosed with IMP at Visits 1 and 4,
i.e., with ~21 d between doses.
There are nine planned visits in this study, starting with Visit 1 (the day of admin istration of the first
IMP dose, Dose 1). Visit 7 on Day 50 (i.e., at Dose 2 + 28 d) was the end of treatment (EoT) visit.
Assessments for safety (physical examination, vital signs, blood/urine clinical laboratory
assessments) were performed at baseline (p re-dose on Day 1) and thereafter at predefined times
until Visit 7. Unsolicited TEAEs reported were recorded from after the first IMP dose until Visit 7.
Solicited local reactions/systemic reactions were recorded continuously using participant diaries
from after the first IMP until Visit 7. The primary reactogenicity endpoints focus on data recorded
up to 7±1 d (Day 8) after each IMP dosing. The primary safety endpoint focuses on unsolicited
TEAE occurring up to 21±2 d after Dose 1 (Day 22) and 28±4 d after Dose 2 (Day 50).
Assessments of binding antibodies, functional antibody titers (neutralizing antibodies), and cell-
mediated immunity (antigen -specific T cells) were performed at baseline (pre -dose on Day 1) and
thereafter at predefined times until Visit 8 (follow -up visit a t 63 d after Dose 2).
Two follow -up visits are planned, one at 63 d after Dose 2 and one at 162 d after Dose 2.
Statistical methods
No formal sample size calculations were performed. The inclusion of 12 participants per dose
group was considered to be adequate for a safety assessment of each IMP per dose level. The
probability to observe a particular TEAE with incidence of 15% at least once in 12 participants per
dose group is 85.8%.
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In Part A, no formal statistical hypothesis was teste d.
In general, data were summarized by dose groups and groups were combined as appropriate.
Continuous variables were summarized by dose group using descriptive statistics. Categorical
variables were summarized by dose group presenting absolute and relativ e frequencies (n and %)
of participants in each category.
Baseline was defined as last available value prior to first dose of IMP.
In general, TEAEs were analyzed by dose group (i.e., by IMP and dose level), for each dose, and
each observation interval, e. g., Day 1 to 21 (pre -Dose 2). Additionally, TEAEs were summarized
for all dose levels combined for each type.
For each analysis, the number and percentage of participants reporting at least one adverse event
(AE) was summarized by preferred term (PT) neste d within system organ class (SOC) for
predefined AE types: any AE, any AE excluding AEs based on solicited reporting via participant
diaries, any related AE, Grade ≥3 AEs, related Grade ≥3 AEs, treatment -emergent serious AEs
(TESAE), TEAEs of special inter est (TEAE-SIs), and related TESAEs. Moreover, the number and
percentage of participants with any AE were summarized by worst grade by PT nested within SOC.
Local reactions and systemic reactions were graded using criteria based on the guidance given in
US FDA Guidance for Industry “Toxicity Grading Scale for Healthy Adult and Adolescent
Volunteers Enrolled in Preventive Vaccine Clinical Trials ”.
For each dose, the number and percentage of participants reporting at least one local reaction or
systemic reacti on (i.e., solicited data collected using participant diaries) were summarized for
predefined reaction types.
Study performance
This study is ongoing clinically. There were six protocol amendments implemented at the
reactogenicity, safety, disposition, and immunogenicity data cut-off for this CSR (23 OCT 2020) .
There were no investigator -reported protocol deviations considered by the sponsor to have
impacted either GCP compliance, participant safety, or the statistical analyses.
Summary of results
Demographi cs
All participants met the inclusion criteria for age, weight, and body mass index (BMI).
In total 120 younger and older participants were treated with BNT162b1 and included in the Safety
Set. All participants met the inclusion criteria for age, weight, a nd BMI. Across the dose groups, the
mean (SD) age was 46.53 (15.94) yrs, the mean (SD) participant weight was 74.28 (12.57) kg, and
the mean (SD) participant BMI was 25.10 (2.70) kg/m2. Of these participants, 57 (48%) were male
and 63 (53%) were female, 11 7 (98%) participants were White (there were 2 Asian and 1 Black
participants), and 118 (98%) participants were not of Hispanic or Latino origin.
In total 96 younger and older participants were treated with BNT162b2 and included in the Safety
Set. All parti cipants met the inclusion criteria for age, weight, and BMI. Across the dose groups, the
mean (SD) participant age was 49.56 (15.01) yrs, the mean (SD) weight was 76.77 (11.15) kg, and
the mean (SD) participant BMI was 25.40 (2.38) kg/m2. Of these particip ants, 44 (46%) were male
and 52 (54%) were female, 96 (100%) participants were White, and 96 (100%) participants were
not of Hispanic or Latino origin.
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Participant disposition
Disposition of younger participants – BNT162b1
AE = adverse ; EoT Visit (Visit 7) completed = end of treatment visit completed (as recorded in the database at the 23 OCT 2020 data
cut-off date) ; N = number of participants ; SAF = safety set; SAFB = safety boost set; Dose 2 + 28 d assessed (CB28) = Dose 2 + 28 d
completer set.
Source: Based on data from Table 14.1-2-1, Table 14.1-3.1-1, and Listing 16.2.1 -1-1.
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Disposition of older participants – BNT162b1
AE = adverse; EoT Visit (Visit 7) completed = end of treatment visit completed (as recorded in the database at the 23 OCT 2020 data
cut-off date) ; N = number of participants ; SAF = safety set; SAFB = safety boost set; Dose 2 + 28 d assessed (CB28) = Dose 2 + 28 d
completer set.
Source: Based on data from Table 14.1-2-1, Table 14.1-3.1-1, and Listing 16.2.3.1 -1-1.
Disposition of younger participants – BNT162b2
AE = adverse ; EoT Visit (Visit 7) completed = end of treatment visit completed (as recorded in the database at the 23 OCT 2020 data
cut-off date) ; N = number of participants; SAF = safety set; SAFB = safety boost set; Dose 2 + 28 d assessed (CB28) = Dose 2 + 28 d
completer set.
Source: Based on data from Table 14.1-2-3, Table 14.1-3.1-3, and Listing 16.2.1 -1-3.
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Disposition of older participants – BNT162b2
EoT Visit (Visit 7) completed = end of treatment visit completed (as recorded in the database at the 23 OCT 2020 data cut-off date) ; N =
number of participants ; SAF = safety set; SAFB = safety boost set; Dose 2 + 28 d assessed (CB28) = Dose 2 + 28 d completer set.
Source: Based on data from Table 14.1-2-3, Table 14.1-3.1-3, and Listing 16.2.1 -1-3.
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For nausea, headache, fatigue, myalgia, chills, arthralgia and malaise each symptom was
assessed as severe in <10% of participants.
A possible dose dependency for both severe fatigue and arthralgia was seen with
0 participants at 10 µg vs. 2 participants at 30 µg, and 0 participants at 10 µg vs.
3 participants at 30 µg, respectively.
Similarly, no clear pattern of dose dependency was seen across the symptom terms for mild
reactions or moderate react ions, with the exception of moderate intensity malaise which was
reported for 1 participant receiving 10 µg and 6 participants with 30 µg dose.
For the 30 µg dose selected for further development, there were consistently slightly higher
rates of reporting systemic reactions than for the next lowest 20 µg level for every individual
symptom term except headache, diarrhoea, fatigue, and fever. The difference is pronounced
for malaise 33% (20 µg) vs. 58% (30 µg) and arthralgia 17% (20 µg) vs. 50% (30 µg).
No ma jor differences were noted between the pattern seen for the combined time intervals
and the individual reporting period.
Older participants and all (younger and older) participants
Overall, in the combined time interval after both doses, the majority of th e older participants
experienced mild (n=25, 69%) followed by moderate (n=13, 36%) solicited systemic reactions. A
few participants experienced severe (n=4, 11%) solicited systemic reactions.
Severe grade systemic reactions were reported in 30 µg (2 partic ipants [17%]) and 10 µg
(2 participants [17%]) dose groups.
The most frequently reported solicited systemic reactions of any severity were fatigue (n=20,
56%), followed by headache (n=17, 47%), malaise (n=12, 33%), and myalgia (n=12, 33%).
The remaining sy mptom terms were less frequent.
Most symptom terms reported were predominantly at mild intensity with a ratio of mild to
moderate reports of between 3:1 and 2:1.
Only mild reactions were reported for diarrhoea and fever.
All symptoms were assessed as sever e in <10% of participants.
For the 30 µg dose selected for further development, there were consistently slightly higher
rates of reporting systemic reactions than for the next lowest 20 µg level for every individual
symptom term. The difference is pronounc ed for moderate malaise 8% (20 µg) vs. 50%
(30 µg).
No major differences were noted between the pattern seen for the combined time intervals
and the individual reporting period.
Note: For BNT162b1, a summary of TEAEs without AEs based on solicited reporti ng via diaries is
given using Safety Dose 2 set (SAFB), because the decision was made not to give the second
60 µg dose (Dose 2).
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the 60 µg dose group, which was only dosed once, neutralizing GMTs remained at a lower level,
indicating that a booster dose is necessary to increase functional antibody titers.
On Day 43 (21 d after Dose 2 BNT162b1), neutralizing GMTs decreased (with exception of the
1 µg dose level). Day 43 neutralizing GMTs were 0 .7-fold (1 µg) to 3.6 -fold (50 µg) those of a
COVID -19 human convalescent serum (HCS) panel.
Participants dosed with BNT162b2 showed a strong IMP -induced antibody response. Virus
neutralizing GMTs were detected after Dose 1 and showed a substantial booster response by 7 d
after Dose 2 (Day 29) for dose level groups ≥3 µg. Day 29 neutralizing GMTs were comparable
between the younger and older participants in the 20 µg dose groups.
On Day 43 (21 d after the second dose of BNT162b2), virus neutralizing GMTs in the younger
adult dose groups decreased for the 3, 20, and 30 µg dose levels. Thereafter, neutralizing GMTs
remained stable up to Day 85 (63 d after the boost) for younger participant dose groups 10, 20,
and 30 µg, and were 1.3 -fold to 1.9 -fold those of a COVID -19 HCS panel.
All participants dosed with Dose 1 at ≥30 µg BNT162b1 or BNT162b2 seroconverted either by 7 d
or 21 d after Dose 2 (Days 29 or 43). All participants immunized with 30 µg BNT162b2 remained
seropositive throughout the follow -up until Day 85.
Exploratory endpoints – Binding antibody concentrations
Binding antibody concentration data is available up until Day 43 for BNT162b1 -dosed younger
participants aged 18 to 55 yrs dosed with 1, 10, 30, 50, and 60 µg on Day 1 (all dose levels) and
Day 22 (all dose levels except 60 µg) (n=12 per group).
For BNT162b2 -dosed participants, data is available for younger participants aged 18 to 55 yrs
dosed with 1, 3, 10, 20, and 30 µg, and older adults aged 56 to 85 yrs dosed with 20 µg on Days 1
and 22 (n=12 per group). Binding antibody data for younger adult participants is available up until
Day 50 for the 1 µg and 3 µg dose groups, and up until Day 85 for the 10, 20, and 30 µg dose
groups. For the BNT162b2 -dosed older participants, data is available up unti l Day 29.
Participants dosed with BNT162b1 showed a strong dose -dependent antibody response against
the SARS -CoV-2 spike (S) protein S1 subunit and receptor binding domain (RBD) at 21 d after
Dose 1 (Day 22). At 7 d after Dose 2 (Day 29), S1 - and RBD -bindi ng immunoglobulin (IgG) GMCs
showed a strong, dose -dependent booster response. In the 60 µg dose group, which was only
dosed once, S1 - and RBD -binding IgG GMCs remained at a lower level, indicating that a booster
dose is necessary to increase antibody conc entrations.
At 21 d after the second BNT162b1 dose (Day 43), S1 - and RBD -binding IgG GMCs decreased
(with exception of the 1 µg dose group), but were clearly above those of a COVID -19 HCS panel
for all dose levels tested.
BNT162b2 dosed participants showed a strong BNT162b2 -induced S1 - and RBD -binding IgG
response at 21 d after Dose 1 (Day 22) with evidence of a dose -dependent response only between
the 1 µg and 10 µg dose levels. S1 - and RBD -binding IgG GMCs showed a substantial booster
response by 7 d afte r Dose 2 (Day 29). Day 29 S1 - and RBD -binding IgG GMCs were comparable
between the younger and older adult 20 µg dose groups. Across all dose groups, antibody levels
decreased over time, but with S1 - and RBD -binding antibody GMCs well above that observed i n a
COVID 19 HCS panel at Day 85 (63 d after Dose 2; 10 µg to 30 µg dose level).
Independent of age, all participants dosed with Dose 1 at ≥20 µg BNT162b1 and or BNT162b2
seroconverted either by 7 d or 21 d after Dose 2 (Day 29 or Day 43).
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Exploratory endp oints – SARS -CoV-2-specific CD4+ and CD8+ T-cell responses
As of 02 MAR 2021, evaluable CD4+ and CD8+ T-cell response data were available from 97 study
participants that received BNT162b1, 70 younger participants at dose levels of 1, 3, 10, 20, 30, 50,
or 60 µg (note: Dose 2 was not given in the 60 µg dose group), and 27 older participants at dose
levels of 10, 20, or 30 µg, as well as 76 participants that received BNT162b2 at dose levels of 1, 3,
10, 20, or 30 µg (47 younger participants), or 10, 20, or 30 µg (29 older participants).
To assess the persistence of cell -mediated immune responses, as of 02 MAR 2021, evaluable
CD4+/CD8+ T-cell response data at Days 85 and 184 (i.e., 9 and 23 wks post -Dose 2, respectively)
are also available for 24 study partici pants that received BNT162b2 (20 younger participants at
dose levels of 10, 20, or 30 µg, and 4 older participants at dose levels of 10, 20, or 30 µg).
The following results are based on assessment of T cell data collected on Day 1 (before Dose 1),
Day 29, Day 85, and Day 184 (i.e., 1, 9, and 23 wks post -Dose 2, respectively).
In both younger and older participants, two doses of BNT162b1 and BNT162b2 induced strong
SARS -CoV-2 RBD -specific and S protein -specific T -cell responses. RBD - and S protein -specific
CD4+ T-cell responses were induced by BNT162b1 in 97.5% of participants and by BNT162b2 in
100% of participants. RBD - and S protein -specific CD8+ T-cell responses were induced by
BNT162b1 in 95.5% of participants and by BNT162b2 in 96.6% of participants.
The T -cell responses elicited by BNT162b2 were directed against additional epitopes of the
S antigen outside RBD, indicating the induction of multi -epitopic responses by BNT162b2 in both
age groups. The magnitude of the T -cell responses did not show clear dose dependency.
Dosing twice with BNT162b1 or BNT162b2 led to a substantial increase in incidence and
magnitude of T -cell responses in both age groups, and across all dose levels for BNT162b1. While
the magnitude of CD4+ T-cell responses induced by BNT162 b2 was also similar across different
dose levels, the magnitude of CD8+ T-cell responses was highest at the 30 µg dose level. The
participants with the strongest CD4+ T-cell responses had more than 10 -fold of the memory
responses observed in the same participants against immunodominant peptides from
cytomegalovirus, Epstein -Barr virus, influenza virus, and tetanus toxoid. The same participants
also had strong CD8+ T-cell responses that were comparable to memory responses against the
above mentioned viral an tigens.
BNT162b2 -induced CD4+ and CD8+ T-cell responses showed a decrease on Day 85, but remained
detectable on Day 184 in almost all participants vaccinated with >10 µg at levels higher than or in
range of recall antigen memory responses.
Exploratory endp oints – Functional and pro -inflammatory CD4+/CD8+ T-cell responses
As of 17 NOV 2020 (BNT162b1) and 02 MAR 2021 (BNT162b2), evaluable functional and pro -
inflammatory CD4+/CD8+ T-cell response data at baseline (before Dose 1) and at Day 29 (28 d
post-Dose 1) are available for 95 study participants that received BNT162b1 (68 younger
participants at dose levels of 1, 3, 10, 20, 30, 50, or 60 µg, and 27 older participants at dose levels
of 10, 20, or 30 µg), as well as for 79 study participants that received BN T162b2 (50 younger
participants at dose levels of 1, 3, 10, 20, or 30 µg, and 29 older participants at dose levels of 10,
20, or 30 µg).
To assess the persistence of cell -mediated immune responses, as of 02 MAR 2021, evaluable
functional and pro -inflammato ry CD4+/CD8+ T-cell response data at Days 43, 85, and 184 (i.e., 3,
9, and 23 wks post -Dose 2, respectively) are also available for 41 study participants that received
BNT162b2 (23 younger participants at dose levels of 10, 20, or 30 µg, and 18 older parti cipants at
dose levels of 10, 20, or 30 µg).
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De novo induction of SARS -CoV-2 S protein or RBD protein directed T cells was confirmed using
ICS. IFN -producing CD4+ and CD8+ T cells against SARS -CoV-2 S protein or RBD were induced
robustly by both BNT162b1 and BNT162b2. No clear dose dependency was observed for both
IMPs. The cytokine responses elicited after dosing with either BNT162b1 or BNT162b2 in older
participants was m ostly identical in response pattern and intensity with that in younger participants.
BNT162b1 and BNT162b2 induced poly -functional and pro -inflammatory CD4+/CD8+ T-cell
responses in almost all participants. The detection of interferon (IFN) , interleukin ( IL)-2 but not
IL-4 indicates a favorable Th1 profile and the absence of a potentially deleterious Th2 immune
response. No notable age -related differences were observed.
BNT162b2 induced poly -functional and pro -inflammatory CD4+/CD8+ T-cell responses in alm ost all
participants persisting in the majority of participants for up to 6 months after Dose 1. The Th1
polarization of the helper T -cell response was characterized by a robust IFN /IL-2 and only minor
IL-4 production upon antigen -specific (wild -type SARS -CoV-2 S protein peptide pools) re -
stimulation which was still observed, although with a reduced magnitude, at later time points.
Conclusions
The majority of events reported were reactogenicity symptoms compared to TEAEs which
were anticipated for IM -admin istered vaccines. The observed reactogenicity was mild or
moderate in severity. The results of this study show that BNT162b1 and BNT162b2 are well
tolerated and have an acceptable safety profile in younger participants aged 18 to 55 yrs and
older participa nts aged 56 to 85 yrs.
The frequency of local and systemic reactogenicity was generally lower for BNT162b2
compared to BNT162b1. BNT162b2 generally had a milder and therefore more favorable
reactogenicity profile than BNT162b1 across dose levels.
Participa nts dosed with BNT162b1 (1 to 50 µg) showed a strong, IMP - and dose -dependent
antibody response in a SARS -CoV-2 neutralization assay by Day 22 (at 21 d after Dose 1).
This response increased further by Day 29 (at 7 d after Dose 2), and the second dose elic ited
a booster effect. By Day 43 (21 d after Dose 2), the observed responses decreased for most
dose levels. For participants dosed at ≥10 µg BNT162b1, Day 43 neutralizing GMTs were
comparable or even superior to those of a COVID -19 HCS panel.
Independent of age, participants dosed with BNT162b2 (1 to 30 µg) showed strong IMP -
induced antibody responses. Virus neutralizing GMTs were detected after Dose 1 and
showed a substantial booster response by 7 d after Dose 2 (Day 29) for dose level groups
≥3 µg. On Da y 43, neutralizing GMTs in the younger participant dose groups decreased for
the 3, 20, and 30 µg dose levels. Thereafter, GMTs remained stable up to Day 85 (63 d after
Dose 2) for younger adult dose groups 10, 20, and 30 µg BNT162b2 and were comparable or
even superior to those of a COVID -19 HCS panel.
After dosing with ≥30 µg BNT162b1 and BNT162b2, all participants showed GMC - and GMT -
based seroconversion by either 7 d or 21 d after Dose 2 (Day 29 or Day 43). All participants
dosed with 30 µg BNT162b2 rem ained seropositive throughout the follow -up until Day 85.
The observed kinetics of the BNT162b1 and BNT162b2 induced neutralizing antibody
response is typical of antigen -activated B cells going through over proliferation, followed by
rebound contraction wi th a gradual decline in numbers before stabilization of the immune
response.
In both younger and older participants, two doses of BNT162b1 and BNT162b2 induced
strong SARS -CoV-2 RBD -specific and S protein -specific T -cell responses. RBD - and
S protein -speci fic CD4+ T-cell responses were induced by BNT162b1 in 97.5% of participants
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Confidential Interim Clinical Study Report - BNT162 -01
Synopsis Page 20 of 20
Version: 3.0
Date: 20 MAR 2021
and by BNT162b2 in 100% of participants. RBD - and S protein -specific CD8+ T-cell
responses were induced by BNT162b1 in 95.5% of participants and by BNT162b2 in 96.6%
of participant s. The magnitude of the T -cell responses did not show clear dose dependency.
BNT162b2 -induced CD4+ and CD8+ T-cell responses showed a decrease on Day 85, but
remained detectable on Day 184 in almost all participants vaccinated with >10 µg at levels
higher than or in range of recall antigen memory responses.
BNT162b1 and BNT162b2 induced poly -functional and pro -inflammatory CD4+/CD8+ T-cell
responses in almost all participants. The detection of IFN and IL -2, but no or only minor IL -4
production, indicates a favorable Th1 profile. No notable age -related differences were
observed.
For the majority of participants, the strong S -specific IFN + and IL -2+CD8+ and Th1 CD4+
T-cell responses contracted by Day 43 (21 d post -Dose 2) and plateaued at a lower level
towar ds Day 85 (63 d post -Dose 2). This observation held true for all dose groups analyzed
with varying response magnitudes between individuals. For the younger participants, the cell -
mediated immune responses remained detectable until Day 184 (162 d post -Dose 2).
The favorable tolerability profile was the major driver for choosing BNT162b2 for further study
in the Phase II/III evaluation of efficacy.
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