Pfizer/BioNTech COVID-19 mRNA vaccine

Overview for ACIP Meeting

Dr Nicholas Kitchin, Pfizer Vaccine Clinical Research & Development

August 26th, 2020
2

Pfizer/BioNTech COVID-19 mRNA vaccine program overview

Focus of large-scale development

Two Vaccine Antigens

SARS-COV-2

Spike Protein 3D Structure

(Wrapp et al., 2020, Science)

Spike Protein Receptor

Binding

Domain (RBD)

Spike-Antigen

Whole Protein

SARS-CoV-2

(3D Model)

Four Vaccine Candidates

Variant Target RNA 

construct Immunization

162a1 RBD subunit uRNA prime / boost

162b1 RBD subunit modRNA prime / boost

162b2 P2-mutated full 

spike protein modRNA prime / boost

162c2 P2-mutated full 

spike protein saRNA single 

injection
3

Two clinical studies assessed the safety, tolerability, and immunogenicity of 

ascending dose levels of BNT162 modRNA vaccine candidates 

* Mulligan, M.J. et al. Phase 1/2 study of COVID-19 RNA vaccine BNT162b1 in adults. Nature https://doi.org/10.1038/s41586-020-2639-4 (2020)

* Walsh EW, Frenck R, Falsey AR, et al. medRxiv 2020.08.17.20176651; doi: https://doi.org/10.1101/2020.08.17.20176651 [preprint].

** Sahin U, Muik A, Derhovanessian E, et al. medRxiv 2020.07.17.20140533; doi: https://doi.org/10.1101/2020.07.17.20140533 [preprint].

• 38 human SARS-CoV-2 infection/COVID-19 convalescent sera from subjects 18-83 years of age

• N=29, 18-55 years of age

• N=9, 56-83 years of age 

• Collected at least 14 days afterBNT P162b CR1-confirmed diagnosis, and at a time when subjects were asymptomatic

• Serum donors predominantly ha BNTd s 162by

2

m? ptomatic infections (35/38), and one had been hospitalized

Human 

COVID-19 

convalescent sera

(HCS)

US Phase 1/2/3 Study*

(C4591001 / NCT04368728)

- 15 healthy participants (18-55 or 

65-85 years of age) per dose level 

[12 active vaccine recipients and 3 

placebo recipients]

- 10 μg, 20 μg, 30 μg, 100 μg

- Immunized on Day 1 and a boost 

dose on Day 21 [No boost for 

100μg cohort]

Germany Phase 1/2 Study**

(BNT162-01 / NCT04380701)

- 12 healthy participants (18-55 or 

56-85 years of age) per dose level

- 1 μg, 10 μg, 30 μg, 50 μg, 60 μg

- Immunized on Day 1 and a boost 

dose on Day 22 ± 2 [No boost for 

60 μg cohort]
4

US Phase 1/2/3 study overview (C4591001 / NCT04368728)

Phase 1 (N=195)

BNT162b1 N=15/group (4:1 randomization active:placebo)

18-55 yrs 10 μg 20 μg 30 μg 100 μg

65-85 yrs 10 μg 20 μg 30 μg

BNT162b2 N=15/group (4:1 randomization active:placebo)

18-55 yrs 10 μg 20 μg 30 μg

65-85 yrs 10 μg 20 μg 30 μg

To describe the safety and tolerability profiles of prophylactic BNT162 vaccines:

• E-diary (local reactions, systemic events incl. fever, use of analgesics/antipyretics)

• Adverse events

• All up to 1 month after last dose

• Serious AEs up to 6 months after last dose

• Hematology & chemistry

To describe the immune responses elicited by prophylactic BNT162 vaccines:

• SARS-CoV-2 neutralizing titers

• S1-binding IgG levels

• RBD-binding IgG levels

Phase 2/3 (N=360/29,286)

BNT162b2 N=180/14,643 group

(1:1 randomization active:placebo)

18-55 yrs ~60% 30 μg

56-85 yrs ~40% 30 μg

To define the safety profile of, and immune responses to, 

prophylactic BNT162b2 vaccine in Phase 2 participants

To evaluate the efficacy of prophylactic BNT162b2 against 

confirmed COVID-19 in Phase 2/3 participants:

• Without evidence of infection before vaccination

• With and without evidence of infection before vaccination

To define the safety profile of prophylactic BNT162b2 vaccine 

in Phase 2/3 participants

• E-diary (local reactions, systemic events incl. fever, use of 

analgesics/antipyretics) – in a subset of at least 6000 

participants

• Adverse events

• All up to 1 month after last dose

• Serious AEs up to 6 months after last dose

Additional secondary & exploratory objectives
5

• To maximize a vaccine’s potential to prevent COVID-19, the following key criteria were evaluated 

in the selection of the final vaccine candidate and dose level: 

–

–

–

Acceptable safety and reactogenicity

SARS-CoV-2 neutralizing titers at or above a human convalescent serum panel (HCS)

Strong TH1-type CD4+ and CD8+ T cell responses

• Both BNT162b1 and BNT162b2 looked strong as vaccine candidates

• However, the totality of data favored the selection of BNT162b2 based on the following findings:

–

–

–

A reactogenicity profile that is more favorable than BNT162b1 in both younger and older adults

A trend towards stronger CD8+ T cell responses

Earlier clearance of SARS-CoV-2 RNA in the nose of BNT162b2 immunized and challenged rhesus

• Based on the totality of data, we chose to advance BNT162b2 at the 30μg dose level

Phase 1 culminated in selection of BNT162b2 30 μg for late stage 

development
BNT162b2 reactogenicity data from C4591001 Phase 1
7

Dose 2

0

20

40

60

80

100

10 20 30 P 10 20 30 P 10 20 30 P 10 20 30 P 10 20 30 P 10 20 30 P

Pain at the injection

site

Redness Swelling Pain at the injection

site

Redness Swelling

Subjects, %

Severe

Moderate

Mild

Note: 1-3 days follow-up 

for 10 μg group 

BNT162b2 shows favorable local reactogenicity profile in Phase 1 (both age groups) Dose 1

0

20

40

60

80

100

10 20 30 P 10 20 30 P 10 20 30 P 10 20 30 P 10 20 30 P 10 20 30 P

Pain at the injection

site

Redness Swelling Pain at the injection

site

Redness Swelling

Subjects, %

Severe

Moderate

Mild

18-55 years 65-85 years
8

Dose 2

0

20

40

60

80

100

10 20 30 P 10 20 30 P 10 20 30 P 10 20 30 P 10 20 30 P 10 20 30 P 10 20 30 P 10 20 30 P

Fever Fatigue Headache Chills Vomiting Diarrhea Muscle pain Joint pain

Subjects, %

Severe

Moderate

Mild

BNT162b2 shows favorable systemic reactogenicity profile in Phase 1 (18-55 years) Dose 1

0

20

40

60

80

100

10 20 30 P 10 20 30 P 10 20 30 P 10 20 30 P 10 20 30 P 10 20 30 P 10 20 30 P 10 20 30 P

Fever Fatigue Headache Chills Vomiting Diarrhea Muscle pain Joint pain

Subjects, %

Severe

Moderate

Mild
9

Dose 2

0

20

40

60

80

100

10 20 30 P 10 20 30 P 10 20 30 P 10 20 30 P 10 20 30 P 10 20 30 P 10 20 30 P 10 20 30 P

Fever Fatigue Headache Chills Vomiting Diarrhea Muscle pain Joint pain

Subjects, %

Severe

Moderate

Mild

Note: 1-3 days follow-up 

for 10 μg group 

BNT162b2 shows favorable systemic reactogenicity profile in Phase 1 (65-85 years) Dose 1

0

20

40

60

80

100

10 20 30 P 10 20 30 P 10 20 30 P 10 20 30 P 10 20 30 P 10 20 30 P 10 20 30 P 10 20 30 P

Fever Fatigue Headache Chills Vomiting Diarrhea Muscle pain Joint pain

Subjects, %

Severe

Moderate

Mild
Immunogenicity data from C4591001 Phase 1
Robust SARS-CoV-2 50% neutralization titers after 2 doses of BNT162b2 in 

Phase 1 exceed those in a human convalescent panel (HCS*)

11

*38 human SARS-CoV-2 

infection/COVID-19 

convalescent sera 
Strong T cell responses shown in German study BNT162-01
13

BNT162b1 induces strong CD4+ and CD8+ T cell responses with TH1 dominance

German Trial, Phase 1, Day 29 (post-dose 2) analysis

c

CD8+ T cells

CD8+ T-cells (Pre- and Post-Vaccination)

Pre 

Post

HCS

0.0

0.2

0.4

0.6

1

2

3

4

5

IFNγ

Per cent IFN

γ

+ of CD8

+ T cells

1.04

0.01

Pre 

Post

HCS

0.00

0.01

0.02

0.03

0.2

0.4

0.6

IL-2

Per cent IL-2

+ of CD8

+ T cells

0.07

0.002

CD4+ T cells

10 μg

30 μg

50 μg

CD4+ T-cells (Pre- and Post-Vaccination)

Pre 

Post

HCS

0.00

0.05

0.10

0.15

0.20

0.25

0.30

IFNγ

Per cent IFN

γ

+ of CD4

+ T cells

0.07

0.01

Pre 

Post

HCS

0.00

0.05

0.10

0.15

0.2

0.4

0.6

IL-2

Per cent IL-2

+ of CD4

+ T cells

0.11

0.03

Pre 

Post

HCS

0.00

0.05

0.10

0.15

0.20

0.25

0.30

IL-4

Per cent IL-4

+ of CD4

+ T cells

0.01

0.002

Human Convalescent Sera (HCS)
14

• Reactogenicity:

–

–

–

–

–

Lower after first vaccination compared to second

Lower in younger than older participants

Profile appears at least as good as approved adult vaccines

• Immunogenicity:

Neutralizing antibody responses 7 days after second dose are robust and exceed 

those observed in a panel of human convalescent sera (38 human SARS-CoV-2 

infection/COVID-19 convalescent sera)

Strong CD4+ and CD8+ T cell responses with TH1 dominance

Phase 1 demonstrated encouraging safety & immunogenicity for BNT162b2, 

supporting advancement to Phase 2/3 
Overview of Phase 2/3
16

US Phase 1/2/3 study overview (C4591001 / NCT04368728)

Phase 1 (N=195)

BNT162b1 N=15/group (4:1 randomization active:placebo)

18-55 yrs 10 μg 20 μg 30 μg 100 μg

65-85 yrs 10 μg 20 μg 30 μg

BNT162b2 N=15/group (4:1 randomization active:placebo)

18-55 yrs 10 μg 20 μg 30 μg

65-85 yrs 10 μg 20 μg 30 μg

To describe the safety and tolerability profiles of prophylactic BNT162 vaccines:

• E-diary (local reactions, systemic events incl. fever, use of analgesics/antipyretics)

• Adverse events

• All up to 1 month after last dose

• Serious AEs up to 6 months after last dose

• Hematology & chemistry

To describe the immune responses elicited by prophylactic BNT162 vaccines:

• SARS-CoV-2 neutralizing titers

• S1-binding IgG levels

• RBD-binding IgG levels

Phase 2/3 (N=360/29,286)

BNT162b2 N=180/14,643 group

(1:1 randomization active:placebo)

18-55 yrs ~60% 30 μg

56-85 yrs ~40% 30 μg

To define the safety profile of, and immune responses to, 

prophylactic BNT162b2 vaccine in Phase 2 participants

To evaluate the efficacy of prophylactic BNT162b2 against 

confirmed COVID-19 in Phase 2/3 participants:

• Without evidence of infection before vaccination

• With and without evidence of infection before vaccination

To define the safety profile of prophylactic BNT162b2 vaccine 

in Phase 2/3 participants

• E-diary (local reactions, systemic events incl. fever, use of 

analgesics/antipyretics) – in a subset of at least 6000 

participants

• Adverse events

• All up to 1 month after last dose

• Serious AEs up to 6 months after last dose

Additional secondary & exploratory objectives
17

Phase 2/3 efficacy schema – started 27 July, 2020

Vaccination period Follow-up period

Up to 2 years 21 days apart

Active surveillance for 

potential COVID-19 

symptoms – triggering 

telehealth or in-person 

visit and nasal swab

• Cases defined based on:

• Presence of symptom(s); and

• Positive SARS-CoV-2 NAAT

• Efficacy analyses in participants:

• Without evidence of infection before 

vaccination; and

• With and without evidence of infection 

before vaccination