125742 45 S211 M5 c4591001 interim ado mth6 synopsis

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Interim Clinical Study  Report
Protocol C4591001
CLINICAL STUDY REPORT SYNOPSIS
CONFIDENTIAL
Page 1Vaccine Name and Compound Number:  BNT162 RNA -Based COVID -19 Vaccines, 
Compound Number: PF-07302048
Report Title:   Interim Report –Adolescent 6 Month Update: A Phase 1/2/3, Placebo-
Controlled, Randomized, Observer -Blind, Dose -Finding Study  to Evaluate the Safet y, 
Tolerability , Immunogenicity , and Efficacy  of SARS -COV -2 RNA Vaccine Candidates 
Against COVID -19 in Healthy  Individuals
Protocol Number: C4591001
Sponsor:  BioNTech SE
Sponsor Agent :  Pfizer Inc
Phase of Development: Phase 1/2/3
First Subject First Visit:  29 April 2020 (study  start); 15 October 2020 (adolescent)
Last Subject Last Visit:   Not applicable
Data Cutoff Date:   02September 2021
Serology Completion Date s:  29October 2021
Coordinating Investigator(s):   Stephen Thomas, MD, SUNY Upstate Medical Universit y, 
725Irving Ave, Ste. 311, Sy racuse, NY 13210
Refer to Appendix 16.1.4.1 for a list of investigators involved in this study .
Study Center(s):  29 in the U nited States for adolescent participants 12 through 15 years of 
age.Refer to Appendix 16.1.4.1 for a list of sites involved in this study .
Date of Current Version: 12December 2021
Date(s) of Previous Report(s): 03December 2021
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Protocol C4591001
CLINICAL STUDY REPORT SYNOPSIS
CONFIDENTIAL
Page 2OBJECTIVES
Study Objectives and Endpoints:  
Phase 1
Phase 1 results are not presented in this report.
Phase 2/3
The study  objective s, estimands, and endpoints presented in Table S1are from Protocol 
Amendment 18.Study  objectives and endpoint analy ses that were either previously  reported, 
or will be reported at a later time, are indicated with gray shading and per the ‘r eference’ 
column .
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Protocol C4591001
CLINICAL STUDY REPORT SYNOPSIS
CONFIDENTIAL
Page 3Table S1. Phase 2/3 Objectives, Estimands, and Endpoints
ObjectivesaEstimands Endpoints Reference
Prim ary Efficacy
To evaluate the efficacy of prophylactic 
BNT162b2 against confirmed 
COVID -19 occurring from 7 days after 
the second dose in participants without
evidence of infection before vaccinationIn participants complying with the key 
protocol criteria (evaluable participants) 
at least 7 days after receipt of the second 
dose of study intervention:  
100 × (1 – IRR) 
[ratio of active vaccine to placebo]COVID -19 incidence per 
1000 person -years of fo llow-up based 
on central laboratory or locally 
confirmed NAAT in participants with 
no serological or virological evidence 
(upto 7 days after receipt of the second 
dose) of past SARS-CoV -2 infectionPrespecified complete efficacy data are 
reported in final analysis interim CSR dated 
03December 2020.
Updated efficacy data arereported in the 
6-month update interim CSR dated 
29April 2021.
Efficacy data from 7 days after Dose 2 to the 
data cutoff date (13 March 2021) for 
participants 12 through 15 years of age only 
are reported in the adolescent interim CSR
dated 14 April 2021 .
To evaluate the efficacy of prophylactic 
BNT162b2 against confirmed 
COVID -19 occurring from 7 days after 
the second dose in participants with and 
without evidence of infection befor e 
vaccinationIn participants complying with the key 
protocol criteria (evaluable participants) 
at least 7 days after receipt of the second 
dose of study intervention:  
100 × (1 – IRR) 
[ratio of active vaccine to placebo]COVID -19 incidence per 1000 
person -years of follow -up based on 
central laboratory or locally confirmed 
NAATInterim data are reported in final analysis 
interim CSR dated 03 December 2020.
Updated efficacy data arereported in the 
6-month update interim CSR dated 
29April 2021.
Efficacy data from 7 days after Dose 2 to the 
data cutoff date (13 March 2021) for 
participants 12 through 15 years of age only 
are reported in the adolescent interim CSR
dated 14 April 2021 .
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Protocol C4591001
CLINICAL STUDY REPORT SYNOPSIS
CONFIDENTIAL
Page 4Table S1. Phase 2/3 Objectives, Estimands, and Endpoints
ObjectivesaEstimands Endpoints Reference
Prim ary Safety
To define the safety profile of 
prophylactic BNT162b2 in the first 
360participants randomized (Phase 2)In participants receiving at least 1 dose 
of study intervention, the percentage of 
participants reporting:
Local reactions for up to 7 days 
following e ach dose
Systemic events for up to 7 days 
following each dose
AEs from Dose 1 to 7 days after the 
second dose
SAEs from Dose 1 to 7 days after the 
second doseLocal reactions (pain at the injection 
site, redness, and swelling)
Systemic events (fever, fatig ue, 
headache, chills, vomiting, diarrhea, 
new or worsened muscle pain, and 
new or worsened joint pain)
AEs
SAEsInterim data are reported in final analysis 
interim CSR dated 03 December 2020.
To define the safety profile of 
prophylactic BNT162b2 in all 
participants randomized in Phase 2/3In participants receiving at least 1 dose 
of study intervention, the percentage of 
participants reporting:
Local reactions for up to 7 days 
following each dose
Systemic events for up to 7 days 
following each dose
AEs fr om Dose 1 to 1 month after the 
second dose
SAEs from Dose 1 to 6 months after 
the second doseAEs
SAEs
In a subset of at least 6000 participants
o Local reactions (pain at the 
injection site, redness, and 
swelling)
o Systemic events (fever, fatigue, 
headache, chills, vomiting, 
diarrhea, new or worsened 
muscle pain, and new or 
worsened joint pain)Interim data are reported up to 1 month after 
Dose 2 and to the data cutoff date 
(14November 2020) in final analysis interim 
CSR dated 03 December 2020.
Cumulative interim data up to cutoff date 
(13March 2021) are reported in the 6 -month 
update interim CSR dated 29 April 2021.
Interim adolescent data for local reactions 
and systemic events reported up to 7 days 
after each dose , and AEs and SAEs are 
reported from Dose 1 to 1 month after Dose 
2 and to the data cutoff date (13 March 2021) 
are reported in th e adolescent interim CSR 
dated 14 April 2021 .
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Page 5Table S1. Phase 2/3 Objectives, Estimands, and Endpoints
ObjectivesaEstimands Endpoints Reference
To define the safety profile of 
prophylactic BNT162b2 in participants 
12 to 15 years of age in Phase 3In participants receiving at least 1 dose 
of study intervention, the percentage of 
participants reporting:
Local reactions for up to 7 days 
following each dose
Systemic events for up to 7 days 
following each dose
AEs from Dose 1 to 1 month after the 
second dose
SAEs from Dose 1 to 6 months after 
the second doseLocal reactions (pain at the injection 
site, redness, and swelling)
Systemic events (fever, fatigue, 
headache, chills, vomiting, diarrhea, 
new or worsened muscle pain, and 
new or worsened joint pain)
AEs
SAEsInterim d ata are reported up to 1month after 
Dose 2 and to the data cutoff date 
(13March 2021) in the adolescent interim 
CSR dated 14 April 2021 .
Interim data for AEs and SAEs reported up 
to 6 months after Dose 2 and to the data 
cutoff date (02 September 2021) are reported 
in this CSR.
To describe the safety and tolerability 
profile of BNT162b2 SAgiven as 1 or 
2doses to BNT162b2 -experienced 
participants, or as 2 doses to 
BNT162b2 -naïve participants
To describe the safety and tolerability 
profile of BNT162b2 given as a third 
dose to BNT162b2 -experienced 
participants in the subset for evaluation 
of boostability and protection against 
emerging VOCsIn participants receiving at least 1 dose 
of study intervention, the pe rcentage of 
participants reporting:
Local reactions for up to 7 days 
following each dose 
Systemic events for up to 7 days 
following each dose
AEs from Dose 1 to 1 month after the 
last dose
SAEs from Dose 1 to 5 or 6 months 
after the last doseLocal reacti ons (pain at the injection 
site, redness, and swelling)
Systemic events (fever, fatigue, 
headache, chills, vomiting, diarrhea, 
new or worsened muscle pain, and 
new or worsened joint pain)
AEs
SAEsInterim data for BNT162b2 given as a third 
dose to BNT162b2-experienced participants 
only are reported up to 1 month after Dose 3 
and to the data cutoff date (17 June 2021) in 
the booster interim CSR dated 
23August 2021.
To describe the safety and tolerability 
profile of BNT162b2 given as a third 
dose at least 6 months after the second 
dose of BNT162b2 (or BNT162b2 SA) 
for participants who received a third 
dose as part of protocol amendment 18In participants receiving at least 1 dose 
of study intervention, the percentage of 
participants reporting:
AEs from Dose 3 to 1 month after 
Dose 3
SAEs from Dose 3 to 6 months after 
Dose 3AEs
SAEsInterim data for BNT162b2 given as a third 
dose to BNT162b2 -experienced participants 
only are reported up to 1 month after Dose 3 
and to the data cutoff date (17June 2021) in 
the booster interim CSR dated 
23August 2021 .
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CLINICAL STUDY REPORT SYNOPSIS
CONFIDENTIAL
Page 6Table S1. Phase 2/3 Objectives, Estimands, and Endpoints
ObjectivesaEstimands Endpoints Reference
Prim ary Immunogenicity
BNT162b2 -experienced participants
To demonstrate the noninferiority of the 
anti–reference strain immune response 
after a third dose of BNT162b2 at 
30µg compared to after 2 doses of 
BNT162b2, in the same individualsGMR of reference strain NT 1 month 
after the third dose of BNT162b2 at 
30µgto 1month after the second dose 
of BNT162b2
The difference in percentages of 
participants with seroresponse to the 
reference s train at 1 month after the third 
dose of BNT162b2 at 30 µgand 1 month 
after the second dose of BNT162b2SARS -CoV -2 reference strain NTs in 
participants with no serological or 
virological evidence (up to 1 month 
after receipt of the third dose of 
BNT162b2 at 30 µg) of past 
SARS -CoV -2 infectionInterim data for BNT162b2 given as a third 
dose to BNT162b2 -experienced participants 
are reported up to 1 month after Dose 3 and to 
the data cutoff date (17 June 2021) in the 
booster interim CSR dated 2 3August 2021 .
To demonstrate the noninferiority of the 
anti-SA immune response after 1 dose 
of BNT162b2 SAcompared to the 
anti-reference strain immune response 
after 2 doses of BNT162b2, in the same 
individualsGMR of SA NT 1 month after 1 dose of 
BNT162b2 SAto the ref erence strain NT 
1 month after the second dose of 
BNT162b2
The difference in percentages of 
participants with seroresponse to the SA 
strain at 1 month after 1 dose of 
BNT162b2 SAand seroresponse to the 
reference strain at 1 month after the 
second dose of BNT162b2SARS -CoV -2 SA and reference strain 
NTs in participants with no serological 
or virological evidence (up to 1 month 
after receipt of 1 dose of BNT162b2 SA) 
of past SARS -CoV -2 infectionData will be reported at a later time.
BNT162b2 -naïve participants
To demonstrate the noninferiority of the 
anti-SA immune response after 2 doses 
of BNT162b2 SAcompared to the 
anti-reference strain immune response 
after 2 doses of BNT162b2 GMR of SA NT 1 month after the 
second dose of BNT162b2 SAto the 
reference strain NT 1 month after the 
second dose of BNT162b2
The difference in percentages of 
participants with seroresponse to the SA 
strain at 1 month after the second dose 
of BNT162b2 SAand seroresponse to the 
reference strain at 1 month after the 
second dose of BNT162b2SARS -CoV -2 SA and reference strain 
NTs in participants with no serological 
or virological evidence (up to 1 month 
after receipt of the second dose of 
BNT162b2 SAor BNT162b2 as 
appropriate) of past SARS-CoV -2 
infectionData will be reported at a later time.
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CLINICAL STUDY REPORT SYNOPSIS
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Page 7Table S1. Phase 2/3 Objectives, Estimands, and Endpoints
ObjectivesaEstimands Endpoints Reference
Secondary Efficacy
To evaluate the efficacy of prophylactic 
BNT162b2 against confirmed 
COVID -19 occurring from 14 days 
after the second dose in participants 
without evidence of infection before 
vaccinationIn participants complying with the key 
protocol criteria (evaluable participants) 
at least 14 days after receipt of the 
second dose of study intervention:
100 × (1 –IRR) [ratio of active vaccine 
to placebo]COVID -19 incidence per 
1000 person -years of follow -up based 
on central laboratory or locally 
confirmed NAAT in participants with 
no serological or virological evidence 
(up to 14 days after receipt of the 
second dose) of past SARS-CoV -2 
infectionPrespecified complete efficacy data are 
reported in final ana lysis interim CSR dated 
03December 2020.
To evaluate the efficacy of prophylactic 
BNT162b2 against confirmed 
COVID -19 occurring from 14 days 
after the second dose in participants 
with and without evidence of infection 
before vaccinationIn participants c omplying with the key 
protocol criteria (evaluable participants) 
at least 14 days after receipt of the 
second dose of study intervention:
100 × (1 –IRR) [ratio of active vaccine 
to placebo]COVID -19 incidence per 
1000 person -years of follow -up based 
on ce ntral laboratory or locally 
confirmed NAATPrespecified complete efficacy data are 
reported in final analysis interim CSR dated 
03December 2020.
To evaluate the efficacy of prophylactic 
BNT162b2 against confirmed severe 
COVID -19 occurring from 7 days and 
from 14 days after the second dose in 
participants without evidence of 
infection before vaccinationIn participants complying with the key 
protoco l criteria (evaluable participants) 
at least 7 days 
and
at least 14 days
after receipt of the second dose of study 
intervention:  100 × (1 –IRR) 
[ratio of active vaccine to placebo]Confirmed severe COVID -19 incidence 
per 1000 person -years of follow -upin 
participants with no serological or 
virological evidence (up to 7 days and 
up to 14 days after receipt of the second 
dose) of past SARS-CoV -2 infectionPrespecified complete efficacy data are 
reported in final analysis interim CSR dated 
03December 2020.
Updated efficacy data occurring from at least 
7 days after the second dose only are 
reported in the 6 -month update interim CSR 
dated 29 April 2021 .
Updated efficacy data occurring from at least 
7 days after the second dose for participants 
12throu gh 15 years of age only are reported 
in theadolescent interim CSR dated 
14April 2021 .
To evaluate the efficacy of prophylactic 
BNT162b2 against confirmed severe 
COVID -19 occurring from 7 days and 
from 14 days after the second dose in 
participants with a nd without evidence 
of infection before vaccinationIn participants complying with the key 
protocol criteria (evaluable participants) 
at least 7 days 
and
at least 14 days
after receipt of the second dose of study 
intervention:  100 × (1 –IRR) Confirmed severe COVID -19 incidence 
per 1000 person -years of follow -upPrespecified complete efficacy data are 
reported in final analysis interim CSR dated 
03December 2020.
Updated efficacy data occurring from at least 
7days after the second dose only are 
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Page 8Table S1. Phase 2/3 Objectives, Estimands, and Endpoints
ObjectivesaEstimands Endpoints Reference
[ratio of active vaccine to placebo] reported in the 6 -month update interim CSR 
dated 29 April 2021 .
Updated efficacy data occurring from at least 
7 days after the second dose for participants 
12through 15 years of age only are reported 
in theadolescent inter im CSR dated 
14April 2021 .
To describe the efficacy of prophylactic 
BNT162b2 against confirmed 
COVID -19 (according to the 
CDC -defined symptoms) occurring 
from 7 days and from 14 days after the 
second dose in participants without
evidence of infection before vaccinationIn participants complying with the key 
protocol criteria (evaluable participants) 
at least 7 days 
and
at least 14 days
after receipt of the second dose of study 
intervention:  100 × (1 –IRR) 
[ratio of active va ccine to placebo]COVID -19 incidence per 
1000 person -years of follow -up based 
on central laboratory or locally 
confirmed NAAT in participants with 
no serological or virological evidence 
(up to 7 days and up to 14 days after 
receipt of the second dose) of p ast 
SARS -CoV -2 infectionPrespecified complete efficacy data are 
reported in final analysis interim CSR dated 
03December 2020.
To describe the efficacy of prophylactic 
BNT162b2 against confirmed 
COVID -19 (according to the 
CDC -defined symptoms) occurring 
from 7 days and from 14 days after the 
second dose in participants with and 
without evidence of infection before 
vaccinationIn participants complying with the key 
protocol criteria (evaluable participants) 
at least 7 days 
and
at least 14 days
after receipt of the second dose of study 
intervention:  100 × (1 –IRR) 
[ratio of active vaccine to placebo]COVID -19 incidence per 
1000 person -years of follow -up based 
on central laboratory or locally 
confirmed NAATPrespecified complete efficacy data are 
reported in final analysis interim CSR dated 
03December 2020.
To evaluate the efficacy of prophylactic 
BNT162b2 against non -S 
seroconversion to SARS -CoV -2 in 
participants without evidence of 
infection or confirmed COVID-19In participants complying with the key 
protocol criteria (evaluable participants):
100 × (1 –IRR) [ratio of active vaccine 
to placebo]Incidence of asymptomatic 
SARS -CoV -2 infection per 
1000 person -years of follow -up based 
on N -binding antibody seroconversion
in participants with no serological or 
virological evidence of past 
SARS -CoV -2 infection or confirmed 
COVID -19Data will be reported at a later time.
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Page 9Table S1. Phase 2/3 Objectives, Estimands, and Endpoints
ObjectivesaEstimands Endpoints Reference
To evaluate the efficacy of prophylactic 
BNT162b2 against asymptomatic 
SARS -CoV -2 infection in participants 
without evidence of infection up to the 
start of the asymptomatic surveillance 
periodIn participants complying with the key 
protocol criteria (evaluable participants):
100 × (1 –IRR) [ratio of active vaccine 
to placebo]Incidence of asymptomatic 
SARS -CoV -2 infection per 
1000 person -years of follow -up based 
on central laboratory –confirmed NAAT 
in participants with no serological or 
virological eviden ce (up to the start of 
the asymptomatic surveillance period) 
of past SARS -CoV -2 infectionData will be reported at a later time.
Secondary Immunogenicity
To demonstrate the noninferiority of the 
immune response to prophylactic 
BNT162b2 in participants 12 to 
15years of age compared to 
participants 16 to 25 years of ageGMR, estimated by the ratio of the 
geometric mean of SARS -CoV -2 
neutralizing titers in the 2 age groups 
(12-15 years of age to 16 -25 years of 
age) 1 month after completion of 
vaccinationSARS -CoV -2 neutralizing titers in 
participants with no serological or 
virological evidence (up to 1 month 
after receipt of the second dose) of past 
SARS -CoV -2 infectionInterim data are reported in the adolescent 
interim CSR dated 14 April 2021.
BNT162b2 -experienced participants
To demonstrate the noninferiority of the 
anti-SA immune response after a third 
dose of BNT162b2 at 30 µgcompared 
to the anti –reference strain immune 
response after 2 doses of BNT162b2, 
inthe same individuals GMR of SA NT 1 month after the third 
dose of BNT162b2 at 30 µgto the 
reference strain NT 1 month after the 
second dose of BNT162b2
The difference in percentages of 
participants with seroresponse to the SA 
strain at 1 month after the third dose of 
BNT162b 2at 30 µgand seroresponse to 
the reference strain at 1 month after the 
second dose of BNT162b2SARS -CoV -2 SA and reference strain 
NTs in participants with no serological 
or virological evidence (up to 1 month 
after receipt of the third dose of 
BNT162b2 at 30µg) of past 
SARS -CoV -2 infectionData will be reported at a later time.
To demonstrate the noninferiority of the 
anti–reference strain immune response 
after 1 dose of BNT162b2 SAcompared 
to after 2 doses of BNT162b2, in the 
same individuals GMR of r eference strain NT 1 month 
after 1 dose of BNT162b2 SAto 1month 
after the second dose of BNT162b2
The difference in percentages of 
participants with seroresponse to the 
reference strain at 1 month after 1 dose 
of BNT162b2 SAand 1 month after the 
second d ose of BNT162b2SARS -CoV -2 reference strain NTs in 
participants with no serological or 
virological evidence (up to 1 month 
after receipt of 1 dose of BNT162b2 SA) 
of past SARS -CoV -2 infectionData will be reported at a later time.
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Page 10Table S1. Phase 2/3 Objectives, Estimands, and Endpoints
ObjectivesaEstimands Endpoints Reference
To descriptively compare the anti-SA 
immune response after 1 dose of 
BNT162b2 SAand a third dose of 
BNT162b2 at 30 µgGMR of SA NT 1 month after 1 dose of 
BNT162b2 SAto 1month after the third 
dose of BNT162b2 at 30 µg
The difference in percentages of 
participants with seroresponse to the SA 
strain at 1 month after 1 dose of 
BNT162b2 SAand 1 month after the third 
dose of BNT162b2 at 30 µgSARS -CoV -2 SA NT in participants 
with no serological or virological 
evidence (up to 1 month after receipt of 
1 dose of BNT162b2 SAor the third dose 
of BNT162b2 at 30 µg) of past 
SARS -CoV -2 infectionData will be reported at a later time.
To descriptively compare the anti-SA 
immune response after 2 doses of 
BNT162b2 SAand the anti –reference 
strain immune response after 2 doses of 
BNT162b2, in the same individuals GMR of SA NT 1 month after the 
second dose of BNT162b2 SAto the 
reference strain NT 1 month after the 
second dose of BNT162b2
The difference in percentages of 
participants with seroresponse to the SA 
strain at 1 month after the second dose 
of BNT162b2 SAand seroresponse to the 
reference strain at 1 month after the 
second dose of BNT162b2SARS -CoV -2 SA and reference strain 
NTs in participants with no serological 
or virologi cal evidence (up to 1 month 
after receipt of the second dose of 
BNT162b2 SA) of past SARS -CoV -2 
infectionData will be reported at a later time.
BNT162b2 -naïve participants
To demonstrate a statistically greater 
anti-SA immune response after 2 doses 
of BNT162b2 SAcompared to after 
2 doses of BNT162b2 GMR of SA NT 1 month after the 
second dose of BNT162b2 SAto 1month 
after the second dose of BNT162b2
The difference in percentages of 
participants with seroresponse to the SA 
strain at 1 month after the second dose 
of BNT162b2 SAand 1 month after the 
second dose of BNT162b2SARS -CoV -2 SA NTs in participants 
with no serological or virological 
evidence (up to 1 month after receipt of 
the second dose of BNT162b2 SAor 
BNT162b2 as appropriate) of past 
SARS -CoV -2 infectionData will be reported at a later time.
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Page 11Table S1. Phase 2/3 Objectives, Estimands, and Endpoints
ObjectivesaEstimands Endpoints Reference
To descriptively compare the 
anti-reference strain immune response 
after 2 doses of BNT162b2 SAand after 
2 doses of BNT162b2 GMR of reference strain NT 1 month 
after the second dose of BNT162b2 SAto 
1 month after the second dose of 
BNT162b2
The difference in percentages of 
participants with seroresponse to 
reference strain at 1 month after the 
second dose of BNT162b2 SAand 
1month after the second dose of 
BNT162b2SARS -CoV -2 reference strain NTs in 
participants with no serological or 
virological evidence (up to 1 month 
after receipt of the second dose of 
BNT162b2 SAor BNT162b2 as 
appropriate) of past SARS-CoV -2 
infectionData will be reported at a later time.
Exploratory
To describe the efficacy of prophylactic 
BNT162b2 against confirmed 
COVID -19 occurring from 7 days after 
the second dose through the blinded 
follow -up period in participants 
without, and with and without , evidence 
of infection before vaccinationIn participants complying with the key
protocol criteria (evaluable participants) 
after receipt of the second dose of study 
intervention:
100 × (1 –IRR) [ratio of active vaccine 
to placebo]COVID -19 incidence per 
1000 person -years of blinded follow -up 
based on central laboratory or locally 
confirmed NAATInterim data arereported in the 6 -month 
update interim CSR dated 29 April 2021.
Updated efficacy data from 7 days after 
Dose 2 through the blinded follow-up period 
for participants 12 through 15 years of age 
are provided in this CSR.
To describe the incidence of confirmed 
COVID -19 through the entire study 
follow -up period prior to receiving the 
third dose of BNT162b2 in participants 
who received BNT162b2 at initial 
randomization or subsequentlyIn participants who received BNT162b2 
(at initial randomization or 
subsequently):
Incidence per 1000 person-ye ars of 
follow -upCOVID -19 incidence per 
1000 person -years of follow -up based 
on central laboratory or locally 
confirmed NAATData will be reported at a later time.
To describe the incidence of confirmed 
COVID -19 after receiving the third 
dose of BNT162b2In participants who received the third 
dose of BNT162b2:
Incidence per 1000 person-ye ars of 
follow -upCOVID -19 incidence per 
1000 person -years of follow -up based 
on central laboratory or loca lly 
confirmed NAATData will be reported at a later time.
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Page 12Table S1. Phase 2/3 Objectives, Estimands, and Endpoints
ObjectivesaEstimands Endpoints Reference
To evaluate the immune response over 
time to prophylactic BNT162b2 and 
persistence of immune response in 
participants with and without
serological or virological evidence of 
SARS -CoV -2 infection before 
vaccinationGMC/GMT and GMFR at baseline and 
1, 6, 12, and 24 months after completion 
of vaccinationFull-length S -binding or S1 -binding 
IgG levels
SARS -CoV -2 neutralizing titersInterim data for Phase 2 (first 
360participants) only up to 1 month after 
Dose 2 are reported for S1 -binding IgG 
levels and SARS -CoV -2 neutralizing titers in 
final analysis interim CSR dated 
03December 2020.
GMTs and GMFRs of SARS -CoV -2 
neutralizing titers up to 1month after Dose 2 
in participants 12 through 15 and 16 through 
25 years of age are reported in the adolescent 
interim CSR dated 14 April 2021 .
To describe the incidence of non -S 
seroconversion to SARS -CoV -2 
through the entire study follow-up 
period in participants who received 
BNT162b2 at initial randomization In participants who received BNT162b2 
at initial randomization:
Incidence per 1000 per son-years of 
follow -upIncidence of asymptomatic 
SARS -CoV -2 infection per 
1000 person -years of follow -up based 
on N -binding antibody seroconversion 
in participants with no serological or 
virological evidence of past 
SARS -CoV -2 infection or confirmed 
COVID -19Data will be reported at a later time.
To describe the efficacy of prophylactic 
BNT162b2 against asymptomatic 
SARS -CoV -2 infection in participants 
with evidence of infection up to the 
start of the asymptomatic surveillance 
periodIn participants complying with the key 
protocol criteria (evaluable participants):
100 × (1 –IRR) [ratio of active vaccine 
to placebo]Incidence of asymptomatic 
SARS -CoV -2 infection per 
1000 person -years of follow -up based 
on central laboratory –confirmed NAAT
in particip ants with serological or 
virological evidence (up to the start of 
the asymptomatic surveillance period) 
of past SARS -CoV -2 infectionData will be reported at a later time.
To describe the serological responses to 
the BNT vaccine candidate and 
characterize the SARS -CoV -2 isolate in 
cases of:
Confirmed COVID-19
Confirmed severe COVID -19
SARS -CoV -2 infection without 
confirmed COVID -19Full S -binding or S1 -binding IgG 
levels
SARS -CoV -2 neutralizing titers
Identification of SARS -CoV -2 
variants(s)Data will be reported at a later time.
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Page 13Table S1. Phase 2/3 Objectives, Estimands, and Endpoints
ObjectivesaEstimands Endpoints Reference
To describe the safety, 
immunogenicity, and efficacy of 
prophylactic BNT162b2 in individuals 
with confirmed stable HIV diseaseAll safety, immunogenicity, and 
efficacy endpoints described aboveSafety data only in participants w ith 
confirmed stable HIV disease are reported in 
the 6 -month update interim CSR dated 
29April 2021.
To describe the safety and 
immunogenicity of prophylactic 
BNT162b2 in individuals 16 to 55 years 
of age vaccinated with study 
intervention produced by manufacturing 
“Process 1” or “Process 2”b AEs
 SAEs
 SARS -CoV -2 neutralizing titersData will be reported at a later time.
To describe the immune response to 
any VOCs not already specifiedGeometric mean NT for any VOCs not 
already specified, after any dose of 
BNT162b2 SAor BNT162b2 SARS -CoV -2 NTs for any VOCs 
not already specifiedData will be reported at a later time.
To describe the immune response to a 
third dose of BNT162b2 (at 30 µg or a 
lower dose of 5 µg or 10 µg) or a third 
or fourth dose of BNT162b2 SA GMTs at Dose 3 and subsequent 
time points
 GMFRs from Dose 3 to subsequent 
time points SARS -CoV -2 reference strai n NTs Interim data for BNT162b2 30 µg given as a 
third dose to BNT162b2 -experienced 
participants are reported in the booster 
interim CSR dated 2 3August 2021 .
To describe the cell -mediated immune 
response, and additional humoral 
immune response parameters, to the 
reference strain and SA in a subset of 
participants:
7 days and 1 and 6 months after 
BNT162b2 SAgiven as 1 or 2 doses 
to BNT162b2 -experienced 
participants
7 days and 1 and 6 months after 
BNT162b2 SAgiven as 2 doses to 
BNT162b2 -naïve participants
7 days and 1 and 6 months after 
BNT162b2 given as a third dose to 
BNT162b2 -experienced 
participantsData will be reported at a later time.
a.HIV-positive participants in Phase 3 were not included in analyses of the objectives, w ith the exception of the specific explorat ory objective.
b.SeeAppendix 16.1.1, Protocol Section 6.1.1 for a description of the manufacturing process.
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Page 14Table S1.Phase 2/3 Objectives, Estimands, and Endpoints
ObjectivesaEstimands Endpoints Reference
Source:  Appendix 16.1.1, Protocol Section 3.2.
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Page 15METHODS
Study Design:  This is a Phase 1/2/3, randomized, multinational, placebo -controlled, 
observer -blind, dose -finding, vaccine candidate –selection, and efficacy  study  in healthy  
individuals.
The study  consists of 2 parts:  Phase 1 to identify  preferred vaccine candidate(s) and dose 
level(s); and Phase 2/3 as an expanded cohort and efficacy  part. The stud y evaluated the 
safet y, tol erabilit y, and immunogenicit y of 3 different SARS -CoV -2 RNA vaccine candidates 
against COVID -19 and the Phase 2/3 efficacy  of 1 selected candidate based on Phase 1 
results:
As a 2 -dose (separated by  21 day s) schedule;
At various dose levels in Phase 1;
As a booster; (data will be reported at a later time)
In various age groups:
Phase 1: 18 to 55 and 65 to 85 y ears of age; 
Phase 2: ≥18 years of age (stratified as 18 to 55 years and >55 to 85 years);
Phase 3: ≥12 years of age (stratified as 12 to 15, 16 to 5 5, or >55 years of age).
To facilitate rapid review of data in real time, Pfizer and BioNTech staff were unblinded to 
vaccine allocation for the participants in Phase 1, and remain blinded for the Phase 2/3 
portion of study  except those who were designated for unblinded activities following the 
protocol and the data blinding plan.
Boostability and Variant Strain Evaluation s
Immunogenicit y and safety evaluations of boostability  were conducted in a subset of Phase 3 
participants at selected sites in the US wh oreceive da third dose of BNT162b2 at 30 µg at 
least 6 months after their second dose, and restuls are reported in the booster interim CSR 
dated 23 August 2021. Evaluations of boostability in Phase 1 participants and a further subset 
of Phase 3 participan ts receiv inga third, lower, dose of BNT162b2 at 5 or 10 µg will be 
reported at a later time.
Evaluations of VOC strains of SARS -CoV -2 (in participants who receive a SARS -CoV -2 
variant encoding vaccine that encodes the Beta variant originally  identified in South Africa 
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Page 16[BNT162b2 SA] as a third dose) are not included in this report and will be reported at a later 
time.
Unblinding Considerations
The study  was to be unblinded in stages once all ongoing participants either had been 
individually  unblinded or had concluded their 6 -month post–Dose 2 or post -Dose 3 study  
visit, in the following sequence :
Phase 1 (after Visit 8 [6- month post -Dose 2 visit]).
Phase 2/3, ≥16 years of age (after Visit 4 [6 -month post -Dose 2 visit]).
Phase 3, 12 through 15 years of age (after Visit 4 [6 -month post -Dose 2 visit]).
Original Phase 3 participants rerandomized to assess boostability  and protection against 
emerging VOCs (after Visit 3 06) (data not included in this report).
Participants who originally  received placebo and became eligible for receipt of BNT162b2 
according to recommendations detailed separatel y, and available in the electronic study 
reference portal, had the opportunity  to receive BNT162b2 in a phased manner as part of the 
study . The investigator ensured the participant met at least 1 of the recommendation criteria 
based upon US recommendation. 
Any Phase 1 placebo recipient who had not already  been offered the opportunity to receive 
BNT162b2 was given this opportunity  no later than at the approximate time participants in 
Phase 2/3 reached Visit 4. Any  Phase 2/3 placebo recipient who had not already  been offered 
the opportunity  to receive BNT162b2 was given this opportunity no later than 6 months after 
Vaccination 2 (at the time of the originall y planned Visit 4).
Any participant who originally  received placebo but then went on to receive BNT162b2 was 
moved to a new visit schedule to receive both doses of BNT162b2 at each of 2additional 
vaccination visits (Visits 101 and 102)
Phase 1
Phase 1 safet y follow -up is ongoing, and participants are expected to participate for up to a 
maximum of approximately  26 months. 
Phase 2/3
The Phase 2 part of the study  was comprised of the first 360 participants enrolled 
(1:1randomization between BNT162b2 and placebo, stratified by  age groups [18 t hrough
55years and >55 t hrough 85 years] with approximately  50% in each age stratum) to assess 
safety data through 7 days after Dose 2 and immunog enicity  data through 1 month after 
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Page 17Dose 2 from these 360 Phase 2 participants. Enrollment continued during Phase 2 and these 
participants were included in the efficacy  evaluation in the Phase 3 part of the study .
Participants in the ongoing Phase 3 part of the study  are ≥12 years of age (stratified as 
12through 15, 16 through 55, or >55 years of age) . The 12 to15 years of age stratum 
comprise dup to approximately  2000 participants enrolled at selected investigational sites . 
Itwas planned to enroll a mini mum of 40% of participants in the > 55 yearsof age stratum . 
Participants in Phase 3 were randomized 1:1 to receive either active vaccine or placebo . 
Efficacy  anal yses for Phase 2/3 part of the study  were event -driven. The prespecified interim 
analysis was conducted on an accrued 94 evaluable COVID -19 cases for the first primary  
efficacy  endpoint (data cutoff date: 04November 2020 ), and the final analy sis was conducted 
on an accrued 170 evaluable COVID -19 cases for the first primary  efficacy  endpoint ( data 
cutoff date : 14November 2020 ). These data are reported in the final analy sis interim CSR 
dated 03 December 2020 and included all study  participants in the efficacy populations 
≥12years of age.
At the time of the fina l analy sis of efficacy  (CSR dated 03 December 2020), relativel y few 
participants 12 to 15 y ears of age had enrolled in the study , and no COVID -19 cases in this 
age group accrued at that time . The adolescent interim CSR dated 14 April 2021 
Noninferiorit y ofimmune response to proph ylactic BNT162b2 in participants 12 to15 years 
of age to response in participants 16 to25 years of age wasassessed based on the GMR of 
SARS -CoV -2 neutralizing titers using a 1.5 -fold margin and reported in the adolescent 
interim CSR dated 14 April 2021 and in an EUA amendment, which supported issuance of 
the EUA for use in individuals 12 to 15 y ears of age. Additionally , the adolescent interim 
CSR dated 14 April 2021 presented updated descriptive efficacy  analy ses for participants 12 
to 15 y ears of age, based on confirmed cases COVID- 19 reported from at least 7 days after 
Dose 2 through the data cutoff date (13 March 2021), with an observed VE of 100% 
irrespective of evidence of prior infection with SARS -CoV -2. No severe COVID-19 cases 
were reported in this age group, based on either protocol definition (ie, per FDA criteria) or 
per CDC criteria for severity . 
Updated efficacy  analy ses during the blinded placebo- controlled follow -up period were 
conducted on cases accrued up to the data cutoff date of 13 March 2021 to evaluate duration 
of protection and reported in the 6-month update interim CSR dated 29 April 2021, which 
presented these anal yses of all confirmed COVID -19 cases and an y cases meeting protocol -
and CDC -defined criteria for severe cases.
It is planned that p articipants would participate in the study for approximately  26months
from the time of enrollment. 
Based on a data cutoff date of 02 September 2021, this interim report for adolescent 
participants 12 to 15 y ears of age summarizes updated descriptive efficacy  anal yses from 
7days after Dose 2 during blinded placebo- controlled follow -up and the following safet y 
data, as ordered:
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Page 18Blinded placebo -controlled follow -up period from Dose 1 to the date of unblinding for 
BNT16 2b2 and placebo participants, including new AEs that were reported after the 
EUA snapshot date (based on events on or after the data cutoff date of 13 March 2021)
Open -label observational follow -up period of original BNT162b2 recipients from the date 
of unblinding to the data cutoff date
Cumulative safety  from Dose 1 to at least 6 months after Dose 2, inclusive of blinded 
data and open -label data for original BNT162b2 recipients, including new AEs that were 
reported after the EUA snapshot date
Open -label observational follow -up period for original placebo recipients who then 
received BNT162b2 from the first dose of BNT162b2 to the data cutoff date
Inclusion/Exclusion Criteria:  
Inclusion Criteria:
Participants were eligible to be included in the study  only if all of the following criteria 
applied:
Age and Sex:
1.Male or female participants between the ages of 18 and 55 y ears, inclusive, 65 and 
85years, inclusive (Phase 1), or ≥12 y ears (Phase 2/3), at randomization.
For the boostability  and protection -against-VOCs subset:
Existing participants enrolled to receive a third dose of BNT162b2 at 30 µg or 
BNT162b2 SA; male or female participants between the ages of 18 and 55 years, 
inclusive, at rerandomization.
Newl y enrolled participants enrolled to receive 2 doses of BNT162b2 SA; male or 
female participants between the ages of 18 and 55 y ears, inclusive, at enrollment.
Existing participants enrolled to receive a third dose of BNT162b2 at 5 or 10 µg; 
male or female participants ≥18 y ears at rerandomization.
Note that participants <18 y ears of age cannot be enrolled in the EU.
Type of Participant and Disease Characteristics:
2.Participants who were willing and able to comply  with all scheduled visits, vaccination 
plan, laboratory  tests, lifesty le considerations, and other study  procedures.
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Page 193.Health y participants who were determined b y medical history, ph ysical examination 
(ifrequired), and clinical judgment of the investigator to be eligible for inclusion in the 
study .
Note : Healthy  participants with preexisting stabl e disease, defined as disease not requiring 
significant change in therapy  or hospitalization for worsening disease during the 6 weeks 
before enrollment, could be included.
4.Phase 2/3 only: Participants who, in the judgment of the investigator, were at highe r risk 
for acquiring COVID -19 (including, but not limited to, use of mass transportation, 
relevant demographics, and frontline essential workers).
5.Boostability and protection -against -VOCs existing participant subset only: 
Participants who provided a serum sample at Visit 3, with Visit 3 occurring within the 
protocol -specified window.
Informed Consent:
6. Capable of giving personal signed informed consent/have parent(s)/legal guardian 
capable of giving signed informed consent which included compliance with the 
requirements and restrictions listed in the informed consent document (ICD) and in the 
protocol.
Exclusion Criteria:
Participants were excluded from the stud y if an y of the following criteria applied:
Medical Conditions:
1.Other medical or psy chiatric condit ion including recent (within the past year) or active 
suicidal ideation/behavior or laboratory  abnormality  that increased the risk of study  
participation or, in the investigator’s judgment, made the participant inappropriate for the 
study .
2.Phases 1 and 2 only: Known infection with HIV, HCV, or HBV.
3.History  of severe adverse reaction associated with a vaccine and/or severe allergic 
reaction (eg, anaph ylaxis) to any  component of the study  intervention(s).
4.Receipt of medications intended to prevent COVID -19.
5. P revious clinical (based on COVID -19 s ymptoms/signs alone, if a SARS -CoV -2 NAAT 
result was not available) or microbiological (based on COVID -19 s ymptoms/signs and a 
positive SARS -CoV -2 NAAT result) diagnosis of COVID -19.
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Page 206.Phase 1 only: Individuals at high risk for severe COVID -19, including those with any  of 
the following risk factors:
Hypertension
Diabetes mellitus
Chronic pulmonary  disease
Asthma
Current vaping or smoking
History  of chronic smoking within the prior y ear
Chronic liver disease
Stage 3 or worse chronic kidney  disease (glomerular filtration rate <60 mL/min/1.73 m2)
Resident in a long- term facility
BMI >30 kg/m2
Anticipating the need for immunosuppressive treatment within the next 6 months
7.Phase 1 only: Individuals currentl y working in occupations with high risk of exposure to 
SARS -CoV -2 (eg, healthcare worker, emergency  response personnel).
8. Immunocompromised individuals with known or suspected immunodeficiency , as 
determined b y history  and/or laboratory /physical examination.
9.Phase 1 only: Individuals with a history  of autoimmune disease or an active autoimmune 
disease requiring therapeutic intervention, including but not limited to: sy stemic or 
cutaneous lupus erythematosus, autoimmune arthritis/rheumatoid arthritis, Guillain -Barré 
syndrome, multiple sclerosis, Sjögren’s s yndrome, idiopathic thrombocytopenia purpura, 
glomerulonephritis, autoimmune thy roiditis, giant cell arteritis (temporal arteritis), 
psoriasis, and insulin -dependent diabetes mellitus (t ype 1).
10. Bleeding diathesis or condition associated with prolonged bleeding that would, in the 
opinion of the investigator, contraindicate intramuscular injection.
11.Women who are pregnant or breastfeeding.
Prior/Concomitant Therapy:
12.Previous vaccination with any coronavirus vaccine.
13.Individuals who received treatment with immunosuppressive therapy , including cy totoxic 
agents or s ystemic corticosteroids, eg, for cancer or an autoimmune disease, or planned 
receipt throughout the study . If systemic corticosteroi ds were administered short term 
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Page 21(<14 days) for treatment of an acute illness, participants should not have been enrolled 
into the study  until corticosteroid therapy  had been discontinued for at least 28 day s 
before stud y intervention administration. I nhale d/nebulized (except for participants in 
Phase 1 – see exclusion criterion 14), intra- articular, intrabursal, or topical (skin or ey es) 
corticosteroids were permitted.
14.Phase 1 only: Regular receipt of inhaled/nebulized corticosteroids.
15.Receipt of blood/plas ma products or immunoglobulin, from 60 day s before study  
intervention administration or planned receipt throughout the stud y.
Prior/Concurrent Clinical Study Experience:
16.Participation in other studies involving study  intervention within 28 day s prior to st udy 
entry  through and including 28 day safter the last dose of study  intervention, with the 
exception of non- Pfizer interventional studies for prevention of COVID 19, which are 
prohibited throughout study  participation.
17.Previous participation in other stud ies involving study  intervention containing lipid 
nanoparticles.
Diagnostic Assessments:
18.Phase 1 only: Positive serological test for SARS- CoV -2 IgM and/or IgG antibodies at 
the screening visit.
19.Phase 1 only: Any screening hematology and/or blood chemistry laboratory  value that 
meets the definition of a ≥Grade 1 abnormality .
Note: With the exception of bilirubin, participants with any  stable Grade 1 abnormalities 
(according to the toxicity  grading scale) may  be considered eligible at the discretion of the 
investigator. (Note: A “stable” Grade 1 laboratory  abnormality  is defined as a report of Grade 
1 on an initial blood sample that remains ≤ Grade 1 upon repeat testing on a second sample 
from the same participant.)
20.Phase 1 only: Positive test for HIV, HBsAg, HBc Abs, or HCV Abs at the screening 
visit.
21.Phase 1 only: SARS -CoV -2 NAAT -positive nasal swab within 24 hours before receipt of 
study  intervention.
Other Exclusions:
22.Investigator site staff or Pfizer/BioNTech employees directly  involved in the conduct of 
the study , site staff otherwise supervised by  the investigator, and their respective famil y 
members. 
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Page 22Vaccines Administered:  The vaccine candidate selected for Phase 2/3 evaluation was 
BNT162b2 at a dose of 30 µg. This report evaluated a 2 -dose (separated b y 21 days) 
schedule of the following for active immunization against COVID -19 or saline placebo: 
BNT162b2 (BNT162 RNA -LNP vaccine containing modRNA that encodes theP2 S): 
30µg
Normal saline (0.9% sodium chloride solution for injection)
A list of the study  interventions administered in this study  and their respective lot numbers is 
provided in Table S2.
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Page 23Table S2. Investigational Product Lot Numbers – Interim – Adolescent 6- Month 
Update
Investigational Product ManufacturerVendor Lot 
Number
(Manufacturer) Lot Numbera(Pfizer)
BNT162b2 (30 µg) BioNTech BCV40720 -A
BCV40720 -A
BCV40720 -B
BCV40720 -C
ED3938
ED3938
ED3938
EE3813
EE3813
EE3813
EE3813
EE3813
ER9449Z
ER9449Z
EE8493Y
EJ0553ZPA2074172/P220395 -0053L
PA2074998/P220395 -0060L
PA2074173/P220395 -0051L
PA2074071/P220395 -0052L
PA2074300/P220395 -0021L
PA2074300/P220395 -0022L
PA2074300/P220395 -0023L
NC2075485/P220395 -0068L
NC2075485/P220395 -0074L
NC2075485/P220395 -0077L
PA2074838/P220395 -0020L
PA2074838/P220395 -0024L
PA2096794/P220395 -0079L
PA2096794/P220395 -0082L
PA2087473/P22039 5-0073L
PA2085061/P220395 -0070L
Placebo (n ormal saline 0.9% 
sodium chloride solution)Pfizer DK2074;20 -002221
DK2074;20 -002221
DK2074;20 -002221
DK2074;20 -002221
DK2074;20 -002221
DK2074;20 -002221
DK2074;20 -002221
DK2074;20 -002221
DK2074;20 -002221PA2069407/P220395 -0032L
PA2069407/P220395 -0033L
PA2069407/P220395 -0034L
PA2069407/P220395 -0044L
PA2069407/P220395 -0045L
PA2069407/P220395 -0046L
PA2069407/P220395 -0055L
PA2069407/P220395 -0062L
PA2069407/P220395 -0065L
Diluent (n ormal saline 0.9% 
sodium chloride solution)Pfizer DK2074
DK1589
DK158920-002221
20-001776
20-001592
Note: C4591001 End of Study Information and Quality Control (QC) Record for Study Drug Appendix 
(Section D) dated 08Oct2021 was used to create this table.
a.     Lot number assigned to the investigational product or diluent by Pfizer Global Clinical Supply.
Protocol C4591001 Investigational Product Lot Numbers Table – Interim –Adolescent 6 -Month Update,
Final, Version 1.0, 15Oct2021.
Efficacy and Immunogenicity Evaluations :  
Efficacy  was assessed based on all cases in participants 12 through 15 y ears of age accrued in 
blinded follow -up to a data cutoff date of 13 March 2021 in the adolescent interm CSR, dated 
14 April 2021. 
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Page 24In this report, updated descriptive efficacy  analyses for participants 12 through 15 years of 
age accrued during blinded placebo -controlled follow -upare summarized up to a data cutoff 
date of 02 September 2021 .
Confirmed COVID -19: presence of at least 1 of the following s ymptoms and SARS -CoV -2 
NAAT -positive during, or within 4 day s before or after, the s ymptomatic period, either at the 
central laboratory or at a local testing facility  (using an acceptable test):
Fever; 
New or increased cough; 
New or increased shortness of breath; 
Chills; 
New or i ncreased muscle pain; 
New loss of taste or smell;
Sore throat;
Diarrhea;
Vomiting.
The second definition, which may  be updated as more is learned about COVID -19, includes 
the following additional sy mptoms defined b y the CDC (listed at 
https://www.cdc.gov/coronavirus/2019 -ncov/s ymptoms- testing/sy mptoms.html):
Fatigue;
Headache;
Nasal congestion or runny  nose;
Nausea. 
Confirmed severe COVID- 19: confirmed COVID -19 and presence of at least 1 of the 
following:
Clinical signs at rest indicat ive of severe s ystemic illness (RR ≥30 breaths per minute, 
HR ≥ 125 beats per minute, SpO 2≤93% on room air at sea level, or PaO 2/FiO 2 
<300 mm Hg);
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Page 25Respiratory  failure (defined as needing high -flow oxy gen, noninvasive ventilation, 
mechanical ventilation, or ECMO);
Evidence of shock (SBP <90 mm Hg, DBP <60 mm Hg, or requiring vasopressors);
Significant acute renal, hepatic, or neurologic d ysfunction;
Admission to an intensive care unit (ICU);
Death.
In addition to the above specified definition of severe COVI D-19, an efficacy  anal ysis for 
any severe COVID -19 cases was conducted using the CDC definition of severe COVID-19 
(hospitalization, admission to the I CU, intubation or mechanical ventilation, or death).
Immunogenicit y evaluations in participants 12 throug h 15 y ears of age are not included in 
this interim report. The immune response to BNT162b2 30 µgin adolescents 12 through 
15years of age was previously  reported to be noninferior (and in fact exceeded) the immune 
response in young adu lts 16 through 25 y ears of age (ie, successful immunobridging), as 
detailed in the adolescent interim report dated 14 April 2021 .
Safety Evaluations: 
Local Reactions and Sy stemic Events: There are no new e -diary  data presented in this report 
(previousl y reported in the adole scent interim CSR, dated 14 April 2021). 
AEs and SAEs : AEs were reported b y the participant (or, when appropriate, by a caregiver, 
surrogate, or the participant's legally  authorized representative). The time period for activel y 
eliciting and collecting AEs and SAEs (“active collection period”) for each participant began 
from the time the participant provided informed consent, which was obtained before the 
participant’s participation in the study  (ie, before undergoing any  study -related procedure 
and/or r eceiving study  intervention), through and including Visit 3 (1 month after Dose 2) for 
Phase 2/3 participants. In addition, any  AEs occurring up to 48 hours after each subsequent 
blood draw were recorded on the CRF. SAEs were collected from the time the pa rticipant
provides informed consent to approximately  6 months after the last dose of study  
intervention ( Visit 4 for Phase 2/3 participants).
For those participants who originall y received placebo but went on to receive BNT162b2 at 
Vaccinations 3 and 4, AEs were collected from the time the participant provide dinformed 
consent (for receipt of Vaccinations 3 and 4) through and including Visit 103 (1 -month 
follow -up after Vaccination 4). SAEs were collected from the time the participant provide d
informed cons ent(for receipt of Vaccinations 3 and 4) to approximately  6 months after the 
second dose of BNT162b2 (Visit 104 ).
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Page 26Acute reactions (immediate AEs) were collected within the first 30 minutes after 
administration of the study  intervention.
Statistical Method s:  
Efficacy Analysis: The efficacy  assessment in Phase 2/3 portion of the study  was event
driven. Vaccine efficacy  (VE)with respect to the first primary  efficacy  endpoint was 
assessed at the first interim analy sis (at least 62 cases) at 94 cases (data cutoff date: 
04November 2020). At the final anal ysis, VE with respect to the first primary  efficacy  
endpoint (at least 16 4cases) was assessed on an accrued 170 evaluable COVID -19 cases 
(data cutoff date: 14 November 2020) and also included VE for the second primary  and all 
secondary  efficacy  endpoints. No additional formal hypothesis testing of clinically  confirmed 
COVID -19cases is planned.
Assessment of VE of BNT162b2 was performed for confirmed COVID -19 cases observed at 
least 7 day s after the receipt of Dose 2 onwards among participants without or with or 
without serological or virological evidence (up to 7 days after re ceipt of the second dose) of 
past SARS -CoV -2 infection. VE was estimated b y 100% × (1 –IRR), where I RR was the 
ratio of COVID -19 illness rate in the BNT162b2 group to the corresponding illness rate in 
the placebo group. 
Efficacy  anal yses during blinded placebo -controlled follow -up were conducted for 
participants 12 through 15 y ears of age based on the data cutoff date of 13 March 2021 
(adolescent interim CSR, dated 14 April 2021). The point estimate of VE in the blinded 
follow -up period and associated 2-s ided 95% CI was derived using the Clopper Pearson 
method adjusted for surveillance time. In addition to the protocol definition of severe 
COVID -19, supportive analy ses using the CDC definition of severe COVID- 19 were also 
performed.
In this report, updated efficacy  anal yses during blinded placebo -controlled follow -up were 
conducted for participants 12 through 15 years of age based on the data cutoff date of 
02 September 2021. In addition to the protocol definition of severe COVID- 19, supportive 
analyses usi ng the CDC definition of severe COVID -19 were also performed.
Immunogenicity Analysis: Immunogenicit y evaluations in participants 12 -15 years of age 
are not included in this interim report. 
Safety Analysis:   The primary safet y objective was evaluated b y descriptive summary  
statistics for local reactions ,systemic events, and AEs/SAEs for each vaccine group. There 
are no new reactogenicity data in this report (previously  reported in the adolescent interim 
CSR, dated 14 April 2021).
Other Analysis : AEs and SAEs reported during the open -label follow -up period were 
summarized separatel y for adolescent participants who were unblinded at the time of being 
eligible for receipt of BNT162b2 according to recommendation s detailed separately , and 
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Page 27available in the electronic study reference portal, or no later than at approximately Visit 4. To 
account for different durations of follow- up time due to unblinding in the study , AEs and 
SAEs during the blinded follow- up period and open label follow -up period were summarized 
as incidence rates adjusted by  exposure time.
RESULTS
AE safet y data are from either the blinded placebo -controlled follow -up period, the 
open -label observational follow -up period, or both. The time periods a nd safety  anal ysis 
groups are presented below and in Figure S1. AEs reported from Dose 1 to 1 month after 
Dose 2 during the blinded placebo- controlled follow -up period w ere previously  reported in 
the adolescent interim CSR, dated 14 April 2021. For each time period, overall safety  will be 
presented in addition to new AEs that were reported since the EUA snapshot occurred (based 
on a data cutoff date of 13 March 2021) , in the following order:
Blinded placebo- controlled follow -up p eriod from Dose 1 to the unblinding date, 
including separate summaries for new AEs that were reported after the EUA snapshot 
date
Open -label follow -up period –original BNT162b2 recipients 
Blinded placebo -controlled and open-label follow -up periods from Dose 1 to 
6months after Dose 2 –original BNT162b2 participants, including separate 
summaries for new AEs that were reported after the EUA snapshot date 
Open -label follow -up period –original placebo recipients who then r eceived at least 
1dose of BNT162b2 after unblinding
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Page 28Figure S1Phase 2/3 Safety Analyses of Adolescent Participants : Time Periods and 
Analysis Groups
Participant Disposition and Demography:  
During th e blinded placebo -controlled follow -up period, median follow -up time for 
adolescent participants was 4.4 months. There were 634 (56.1%) and 629 (55.7%) of 
participants in the BNT162b2 and placebo groups, respectivel y, who had f ollow -up time 
between ≥4 months to <6 months after Dose 2. From Dose 2 to the cutoff date, 740 (65.4%) 
of participants in the BNT162b2 group had a total f ollow -up time between ≥8 to <10 months, 
which was composed of blinded and unblinded exposure. There were few participants 
(18total) with follow -up time of <6 months, as most adolescent participants 12 -15 years of 
age should have had ≥6 months of follow -up by  the data cutoff date (02 September 2021), 
and also corresponding with the number of participants who withdrew from the stud y.
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Page 29Disposition – Blinded Placebo- Controlled Follow -UpPeriod
During the blinded placebo -controlled follow -up period, there were 3 (0.3%) participants in 
the BNT162b2 group and 14 (1.2%) participants in the placebo group who discontinued from 
the vaccinatio n period (Dose 1 to 1 month after Dose 2). Most participants completed the 
visit at 1 month after Dose 2 ( ≥97.0%). Few participants in the BNT162b2 and placebo 
groups were withdrawn from the study  (0.4% and 1.2%, respectively ), and all were because 
ofwithdrawal b y the participant, withdrawal b y parent/guardian, or they  were lost to 
follow -up.
Disposition – Open -Label Follow -Up Period
Individuals have been unblinded asthey became locally  eligible and wish edto know their 
vaccine assignment to confirm prior vaccination with BNT162b2 (if randomized to this 
group), or to receive BNT162b2 (if randomized to placebo). Participants who originally  
received BNT162b2 continue dto be followed in an open -label manner. Participant swho 
origin ally received placebo were offered BNT162b2 vaccination (Doses 3 and 4 [first and 
second dose of BNT162b2 30 µg, respectivel y]) and thereafter followed in an open -label 
manner.
Most participants in the BNT162b2 (98.1%) and placebo (97.0%) groups completed the 
1month post -Dose 2 visit before unblinding. 
A total of 4 (0.4%) original BNT162b2 adolescent participants received Dose 1 of 
BNT162b2 during the blinded placebo -controlled follow -up period and then received Dose 2 
of BNT162b2 30 µg during the open- label follow -up period (when they  were unblinded). 
There were 45 (4.0%) participants withdrawn from the study , and most were because of other 
reasons (21 of 23 participants were enrolled into Study  C4591031 to evaluate a booster dose 
of BNT162b2).
During the open- label follow -up period, most participants originally  randomized to the 
placebo group received Doses 3 and 4 (89.4% and 87.8%, first and second dose of 
BNT162b2 30 µg, respectively ). There were 47 (4.2%) participants who were withdrawn 
from the study  after unblinding and before Dose 3. There were few participants in this group 
(who received at least the first dose of BNT162b2 30 µg)who were withdrawn from the 
study who (0.5%) , and most were because of withdrawals by  the participant, or they  were 
lost to follow -up. 
Demographics – Safety Population
Overall
Demographic characteristics for adolescents (12 -15 years of age) were similar in the 
BNT162b2 and placebo groups in the safet y population, and all adolescents were enrolled at 
sites in the United States. Most adolescent participants in the BNT162b2 group were White 
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Page 30(85.8%), with 4.6% Black or African American participants and 6.4% Asian participants , and 
other racial groups were ≤2.1%. There were 11.7% Hispanic/Latino participants. The m edian 
age of adolescents in the BNT162b2 group was 14.0 years and 50.1% were male. Obese 
adolescents of this age group (based on age -and sex -specific BM I)made up 11.3% (placebo 
group) to 12.6% (BNT162b2 group) .
Participants With At Least 6 Months Follow -Up T ime –Original BNT162b2 Participants
Demographic characteristics for all original BNT162b2 adolescent participants who had at 
least 6 months of follow- up time after Dose 2 were similar to demographic characteristics in 
the BNT162b2 group overall.
Original Placebo Participants W ho Then Received BNT162b2
Demographic characteristics for all original placebo adolescent participants who then 
received BNT162b2 later during the open -label follow -up period were similar to 
demographic characteristics in the placebo group overall.
Evaluable Efficacy (7 Days )Population –Blinded Placeb o-Controlled Follow -Up Period
Demographic characteristics in the evaluable efficacy  (7 day s) population for adolescent 
participants without evidence of infection prior to 7 day s after Do se 2 w ere similar in the 
BNT162b2 and placebo groups. This anal ysis population had generally  similar demographics 
compared with the safet y population.
Efficacy Results – Updated Analysis :  
In the updated descriptive efficacy  anal ysis (data cutoff date 0 2September 2021), among 
participants in the evaluable efficacy  population without evidence of SARS -CoV -2 
infection before and during the vaccination regimen, the estimated VE against confirmed 
COVID -19 occurring at least 7 day s after Dose 2 was 100% (2 -sided 95% CI : 86.8%, 
100%), with 0 cases in the BNT162b2 group and 28 cases in the placebo group. Among 
participants with or without evidence of SARS -CoV -2 infection before and during the 
vaccination regimen, the estimated VE against confirmed COVID -19 occurri ng at least 7 
days after Dose 2 was 100% (2-sided 95% CI: 87.5%, 100%), with 0 and 30 cases in the 
BNT162b2 and placebo groups, respectively.
Among participants without and with or without evidence of SARS -CoV -2 infection 
before and during the vaccination regimen (evaluable efficacy  population), VE against 
COVID -19 occurring at least 7 day s after Dose 2 was evaluated for demographic and risk 
subgroups, and the estimated VE was 100.0% for all subgroups .
From the analysis of all cases of confirmed COVID -19 based on the all- available 
(modified intention -to-treat) population (regardless of evidence of infection before or 
during the vaccination regimen), the estimated VE against all cases occurring at an y tim e 
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Page 31after Dose 1 was 94.0% (2- sided 95% CI: 81.3%, 98.8%), with 3 cases in the BNT162b2 
group (all occurring within <11 day s after Dose 1 and in participants who had baseline 
SARS -CoV -2 negative status) and 48 cases in the placebo group.
No severe COVID -19 cases (per protocol definition or CDC criteria) were reported in 
participants 12 -15 years of age as of the data cutoff date (02 September 2021) .
Most variants sequenced were neither VOI nor VOC except for the B.1.1.7 (Alpha) found 
in 23.3% of placebo partic ipants. A ll of the cases in the efficacy  anal yses occurred 
between 02 November 2020 to 19 May  2021, which is before the Delta surge in the US. 
Safety Results:  
Blinded Placebo -Controlled Follow -Up Period From Dose 1 to the Unblinding Date –
Participants 12 Through 15 Years of Age
Adverse Events
Total exposure time in 100 PY was similar in the BNT162b2 and placebo groups (4.6 vs 
4.5per 100 PY, respectively ). Hence, frequencies aresummarized in the safety  results . 
The percentage of adolescent participants with any  AE was similar in the BNT162b2 and 
placebo groups (8.4% and 10.0%, respectively ). Severe AEs, SAEs, and AEs leading to 
withdrawal were reported by  ≤1.1%, ≤0.9%, and ≤0.1%, respectively , in both groups. All 
reported SAEs were assessed by the investigator as not related to study intervention. 
Withdrawals due to related AEs were reported in 1 adolescent participant in the BNT162b2 
group (p yrexia occurring 1 day after Dose 1; previously reported in adolescent interim CSR 
dated 14 April 202 1), and none in the placebo group. There were no deaths.
The most frequentl y reported AEs in the BNT162b2 group included ly mphadenopathy  
(9[0.8%]), injection site pain (8 [0.7%]), fatigue (8 [0.7%]), py rexia (6 [0.5%]), depression 
(6[0.5%]), nausea (5 [0.4%]), and headache (5 [0.4%]). Most of these AEs were previousl y 
reported in the adolescent interim CSR, dated 14 April 2021. 
The number of participants with psy chiatric disorder AEs were comparable in the 2 groups, 
(17 [1.5%] in BNT162b2 group vs. 13 [1 .2%] in placebo group). There were 4 participants 
who were hospitalized with the event of suicidal ideation (3 of these were new after the EUA 
snapshot). All participants were in the BNT162b2 group and had an ongoing past medical 
history  of depression and/ or anxiety  (3diagnosed within 2020 and 1 since 2018). Of these 
4participants, 3 had been taking selective serotonin reuptake inhibitors (fluoxetine or 
sertraline) for their ongoing condition.  The fourth participant had their concomitant 
medication for a ttention deficit hy peractivity  disorder changed from methylphenidate 
hydrochloride to demethy lphenidate hy drochloride approximately  22 day s before the event of 
suicidal ideation occurred.
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Page 32A total of 9 participants reported depression: 6 [0.5%] in the BNT16 2b2 group and 3 [0.3%] 
in the placebo group , (6 of these were new after the EUA snapshot; 4 in the BNT162b2 group 
and 2 in the placebo group. Of the 6 participants in the BNT162b2 group 3 participants had a 
known past medical history  of ongoing depression, and of the 4 newly  diagnosed cases in the 
BNT162b2 group , 3participants had an ongoing past medical history  of attention deficit 
hyperactivit y disorder and the depression for the remaining participant in this group was 
reported to be due to social events . Within the placebo group, 2 of the 3 participants were 
newly  diagnosed with depression.
The event of conversion disorder (BNT162b2 group) has been previousl y reported in the 
adolescent interim CSR dated 14 April 2021 ,as an SAE of neuralgia and had been 
extensively  investigated. Further follow -up since the adolescent interim CSR; the participant 
was continuing with physical therap y and had undergone further neurological examination 
and investigations including an MRI brain scan with and without contrast that was normal. 
There has been little change in her s ymptoms, and she continues to require treatment.
The 1 participant in the BNT162b2 group who reported a tic had an exacerbation of their 
known tic disorder (diagnosed since 2019) and was considered to be due to life stressors (as 
determined b y the principal investigator) . This event was previousl y reported in the 
adolescent interim CSR dated 14 April 2021.
Subgroup Analyses
Forthe baseline SARS -CoV -2 positive and negative subgroups, AEs b y SOC and PT wer e 
similar to those in the overall safety population. Considering that the positive subgroup 
(N=46) had fewer participants than the negative subgroup (N=1083) in the BNT162b2 group, 
differences in SOCs were considered not clinically  meaningful, and there is no evidence that 
individuals who are positive at baseline report AEs at a higher frequency  than those who are 
negative at baseline.
For the ethnicit y subgroups, AEs by SOC and PT were similar to those in the overall safet y 
population for Hispanic/Latino a nd non- Hispanic/non -Latino participants. Considering that 
the Hispanic/Latino subgroup (N=132) had fewer participants than non -Hispanic/non -Latino 
subgroup (N=99 7) in the BNT162b2 group, differences in AEs by  SOC and PT in these 
subgroups were not clinical ly meaningful. 
For race subgroups, AEs by  SOC and PT were similar to those in the overall safet y 
population. Considering that some race subgroups had fewer participants than others (within 
the BNT162b2 groups: White N=970, Black or African American N=52, and ‘All Others’ 
N=109), differences in AEs by  SOC and PT in these subgroups were not clinically  
meaningful. 
For sex subgroups, AEs by  SOC and PT were similar to those in the overall safet y 
population. There was a slightly  higher frequency of any  event re ported in the BNT162b2 
group in female participants compared to males (53 [9.4%], 42 [7.4%] respectivel y), and of 
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Page 33any SAEs 7 (1.2%) females, 3 (0.5%) males. Within the placebo group there were 2 (0.3%) 
SAEs reported in male participants and none in the fem ales. In the BNT162b2 group, 
lymphadenopathy  was reported in 8 (1.4%) male participants and in 1 (0.2%) female 
participant. AEs in the psy chiatric disorders SOC were reported in 12 (2.1%) female 
participants compared to 5 (0.9%) male participants. Depressi on was the most frequentl y 
reported event in both sexes (4 [0.7%] females and 2 [0.4%] males). Anxiety  was reported in 
4 (0.7%) females and no males. Suicidal ideation was the next most frequently  reported 
event: in females, 3 [0.5%], 1 (0.2%) in males. 
New Adverse Events After the EUA Snapshot
The frequency  of adolescent participants in the BNT162b2 group with an y new AE after the 
EUA snapshot from Dose 1 to the unblinding date was 2.6%, which was less than the 
frequency  in the placebo group (4.2%). There were 6 (0.5%) participants in the BNT162b2 
group with SAEs, and all events were assessed b y the investigator as not related to study  
intervention. No SAEs were reported in the placebo group. There were no withdrawals 
because of an y AEs or deaths.
The most frequentl y reported AEs in adolescents were in the ps ychiatric disorders SOC 
(11[1.0%] and 9 [0.8%] adolescent participants in the BNT162b2 and placebo groups, 
respectivel y).
No new safet y signals or concerns were for new AEs reported after the EUA snaps hot.
Open -Label Follow -Up Period From the Unblinding Date to the Data Cutoff Date–
Original BNT162b2 Recipients 12 Through 15 Years of Age
There were 18 (1.6%) participants who experienced an y AE, including 0.4%, 0.3%, and 0% 
who experienced related, sever e, and life -threatening events, respectivel y. This is markedly  
reduced relative to AEs from Dose 1 to the unblinding date (8.4% of BNT162b2 participants 
experienced an y AE, including 3.2%, 1.1%, and 0.2% who experienced related, severe, and 
life-threatening events, respectivel y). The frequencies of SAEs and AEs leading to 
withdrawal during the open -label follow -up period (0. 4% and 0%, respectively ) were similar 
to those from Dose 1 to the unblinding date (0.9% and 0.1%, respectivel y). There were no 
adolescent deaths in the study .
Overall, the rates in all SOCs after the unblinding date were lower or remained similar to 
those in the blinded placebo- controlled period. 
The frequency  for the SOC of nervous s ystem disorders was 6 (0.5%), including the PTs 
dizziness (2), headache (2), pres yncope (2), and syncope (1). The frequency for the SOC of 
general disorders and administration site conditions was 4(0.4%) , with injection site pain (3) 
as the most frequentl y reported PT.
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Page 34Blinded Placebo -Controlled and Open -Label Follow -Up Periods to 6 Months After Dose 2 
–Original BNT162b2 Recipients 12 Through 15 Years of Age
Adverse Events
There were 1113 adolescent participants who originally  received BNT162b2 and had at least 
6 months of follow -up time after Dose 2 forthe blinded placebo- controlled and open -label 
follow -up periods. There were 98 (8.8%) participants who reported at least 1 A E, and 34 
(3.1%) participants reported at least 1 related AE . Severe AEs and SAEs were reported b y 13 
(1.2%)and 10(0.9%) participants ,respectivel y. There were no AEs leading to withdrawal, 
and there were no deaths.
The frequenc iesof any AEs and related AE sare70(6.3%) and 34 (3.1%) through 1 month 
after Dose 2 compared with 35 (3.1%) and no related AEs fr om 1 month after Dose 2 to 
6months after D ose 2 ,respectively . From Dose 1 to 1 month after Dose 2, 3 
(0.3%) adolescent participants reported SAEs . From 1 month to 6 months after Dose2,
9(0.8%) participants reported SAE s. AllSAEs were assessed b y the investigator as not 
related to stud y intervention. There were no AEs leading to withdrawal, and there were no 
deaths.
Frequently  reported AEs i ncluded reactogenicit y events in the following SOCs:
general disorders and administration site conditions ( 16 [1.4%] )
musculoskeletal and connective tissue disorders ( 8 [0.7 %])
nervous s ystem disorders ( 16 [1.4%])
gastrointestinal disorders ( 16 [1.4 %])
AEs were reported by 15 (1.3%) participants in the injury, poisoning, and procedural 
complications SOC; 10 (0.9%) participants in the infections and infestations SOC, and 
16(1.4%) participants in the psy chiatric disorders SOC. 
All ly mphadenopathy  events wer e reported from Dose 1 to 1 month after Dose 2, and none 
were reported from 1 month to 6 months after Dose 2. 
AEs in the p yschiatric disorders SOC were reported by7 (0.6%) participants from Dose 1 to 
1month after Dose 2 and in 11 (1.0%) participants from 1 month to 6 months after Dose 2. 
Overall, AEs reported after 1 month post Dose- 2 reflect age -appropriate events consistent 
with the general population. 
New Adverse Events After the EUA Snapshot
From the time after the EUA snapshot for adolescent participants who had at least 6 months 
of follow -up time after Dose 2 during the blinded placebo -controlled and open -label 
follow -up periods, there were 36 (3.2%) participants who reported at least 1 AE, and 
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Page 353(0.3%) participants reported at least 1 relate d AE . Severe AEs and SAEs were reported b y 
6(0.5%) and 7 (0.6%) participants ,respectively . There were no AEs leading to withdrawal, 
and there were no deaths.
When frequencies of new AEs for participants with at least 6 months of follow -up time are 
exami ned by  time since the second dose, the frequency  of an y AEs and related AEs is 
6(0.5%) and 3 (0.3%) through 1 month after Dose 2 compared with 32 (2.9%) and no related 
AEs from 1 month after Dose 2 to 6 months after Dose 2. At 1 month after Dose 2, no 
adolescent participants reported severe AEs or SAEs. From 1 month to 6 months after 
Dose 2, the number of participants with severe AEs and SAEs was 6 (0.5%) and 7 (0.6%), 
respectivel y. All new SAEs and all AEs reported from 1 month after Dose 2 to 6 months af ter 
Dose 2 were assessed b y the investigator as not related to study  intervention.
Most of the new AEs reported after the EUA snapshot in adolescent participants with at least 
6 months of follow -up time after Dose 2 were in the psy chiatric disorders SOC (11 [1.0%]) .
When AEs are compared from Dose 1 to 1 month after Dose 2 and from 1 month after 
Dose 2 to 6 months after Dose 2, AEs reported in the psy chiatric disorders SOC was 
1(0.1%) and 10 (0.9%) participants, respectivel y.All AEs in this SOC were asses sed b y the 
investigator as not related to study  intervention.
Open -Label Follow -Up Period – Original Placebo Recipients 12 Through 15 Years of A ge
Who Then Received BNT162b2 After Unblinding
For the 1,010 original placebo recipients who then received BNT162b2 after unbli nding, the 
total exposure time is shorter than those who originally  received BNT162b2 (2.9 per 100 PY 
vs 4.6 per 100 PY, respectively .
After participants who originall y received placebo were unblinded and then received 
BNT162b2 after un blinding, events related to reactogenicit y were not reported using an 
e-diary  but were instead reported as AEs. Because an e -diary  was not used after original 
placebo recipients received open -label BNT162b2, in comparison to participants randomized 
to BNT1 62b2 from Dose 1 to the unblinding date, the frequencies for an y AE and at least 
1related AE for participants who originall y received placebo and then received BNT162b2 
are greater (26.2% and 24.0%) than the frequencies (8.4% and 3.2%) for participants wh o 
originall y received BNT162b2, respectivel y. However, the frequencies for severe, life -
threatening AE, SAE, AEs leading to withdrawal and deaths were similar (1.2%, 0%, 0.6%, 
0%, 0% v ersus 1.1%, 0.2%, 0.9%, 0.1%, 0% , respectivel y). There was 1 related SAE of 
appendicitis for a placebo recipient who was vaccinated with BNT162b2.
Most AEs reported from Dose 3 (first dose of BNT162b2) to the data cutoff date were in 
SOCs with reactogenicity  events.
general disorders and administration site conditions ( 225 [22.3%] )
nervous s ystem disorders ( 75 [7.4%] )
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Page 36musculoskeletal and connective tissue disorders ( 48 [4.8%] )
gastrointestinal disorders (20 [2.0%])
The most frequentl y reported AEs overall were injection site pain (15.5%), fatigue (10.3%), 
headache (7.0%), p yrexia (6.3%), chills (4.5%), my algia (3.8%), pain (3.5%), nausea (1.2%), 
pain in extremity  (0.9%), vomiting (0.7%), malaise (0.7%), and injection site ery thema 
(0.5%).
Other Significant Adverse Events
Adverse events of clinical interest include AESIs , such as those in the CDC list of AESI s for 
COVID -19thatinclude events potentially  indicative of severe COVID -19 or autoimmune 
and neuroinflammatory  disorders, were considered , in addition to program- defined TMEs, in 
the review of reported events for the adol escent group .
No cases of anaph ylaxis, hy persensitivity , Bell’s palsy , or vaccine -related appendicitis were 
reported as of the data cutoff date (02 September 2021) during the blinded placebo -controlled 
period.
FDA -Requested Adverse Events of Clinical I nterest
Lymphadenopathy
Lym phadenopathy  is identified as an adverse reaction for BNT162b2 vaccine.
During the blinded placebo -controlled follow -up period, 9 and 2 participants in the 
BNT162b2 and placebo groups reported AEs of lymphadenopath y, respectively. All events 
were mild or moderate in severit y (onl y 1 moderate AE in the BNT162b2 group).
Appendicitis
During the blinded placebo -controlled follow -up period, 2 participants in the placebo group 
each had an SAE of appendicitis, and both events were assessed by the investigator as not 
related to stud y intervention.
During the open- label follow -up period:
Two original BNT162b2 recipients each had an SAE of appendicitis long after 
vaccination from Dose 2 (Day 148 and Day 177), and both events were assessed by  
the investigator as not related to study  intervention.
One original placebo recipient had an SAE of appendicitis that was assessed by  the 
investigator as related to study  intervention.
090177e198d9ed94\Approved\Approved On: 13-Dec-2021 02:30 (GMT) 
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Interim Clinical Study  Report
Protocol C4591001
CLINICAL STUDY REPORT SYNOPSIS
CONFIDENTIAL
Page 37Myocarditis/pericarditis
One original placebo participant had an SAE of myocarditis (previousl y reported to CBER 
and discussed b y AC IP) on Day 3 after Dose 4 (second dose of BNT162b2 30 µg), which 
was assessed b y the investigator as not related to study  intervention (Pfizer assessed event as 
related to stud y intervention).
Other Adverse Events of Clinical Interest
Additional AEs of clinical interest, including those on the CDC AESI  list, were evaluated based 
on sponsor agent safet y data review. These AEs were identified from the C4591001 study  
database as of the data cutoff date (02 September 2021). From this anal ysis, notable pertinent 
negatives (ie, no cases reported in this population as of the data cutoff for this submission) with 
regard to the CDC list of AESI s included (but were not limited to): thromboembolic or 
intravasc ular coagulation events, autoimmune or demy elination events, meningitis, encephalitis, 
optic neuritis, Kawasaki disease, MIS -C, or acute respiratory  distress s yndrome.
An anal ysis of AEs of clinical interest for potential numerical imbalance (based on risk
difference >0) between BNT162b2 and placebo SOC and PT showed no numerical difference 
for most PTs in the BNT162b2 and placebo groups. SOCs which did include PTs more 
frequentl y reported after BNT162b2 compared to placebo, or otherwise considered of parti cular 
clinical interest, are summarized below.
There was a numerical difference for events of p yrexia, which was reported by  6 participants 
in the BNT162b2 group and none in the placebo group. These are recognized as 
reactogenicity  events known to be assoc iated with BNT162b2 vaccination.
There was no imbalance of arthralgia being reported more frequentl y in the BNT162b2 
group.
Overall Conclusion(s):  
In Phase 2/3, updated descriptive efficacy  anal ysis continues to show that BNT162b2 at 
30 µg provided a hig h level of protection against COVID-19 in participants 12 through 
15 years of age with or without evidence of infection with SARS -CoV -2(100% VE), 
with no severe cases overall observed in this age group.
The tolerability  and safety  profile of BNT162b2 30 µg in participants 12 through 
15years of age at up to 6 months after Dose 2 was acceptable throughout the follow-up 
period (to the data cutoff date) and consistent with results previously  reported. 
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