Page 35 - pfizervax

PF-07302048 (BNT162 RNA-Based COVID-19 Vaccines)
Protocol C4591001

Two SARS-CoV-2–RNA lipid nanoparticle (RNA-LNP) vaccines based on a platform of
nucleoside-modified messenger RNA (modRNA, BNT162b) will be evaluated in this study.
Each vaccine candidate expresses 1 of 2 antigens: the SARS-CoV-2 full-length, P2 mutant,
prefusion spike glycoprotein (P2 S) (version 9) or a trimerized SARS-CoV-2 spike
glycoprotein-receptor binding domain (RBD) (version 5). The 2 SARS-CoV-2 vaccine
candidates that will be tested in this study are therefore:

• BNT162b1 (variant RBP020.3): nucleoside-modified messenger RNA (modRNA)
with blunted innate immune sensor–activating capacity and augmented expression
encoding the RBD.

• BNT162b2 (variant RBP020.2): nucleoside-modified messenger RNA (modRNA) as
above, but encoding P2 S.

The vaccine candidate selected for Phase 2/3 evaluation is BNT162b2.

2.2.1. Clinical Overview

Prior to this study, given clinical data from other similarly formulated uRNA liposomal
6
vaccines from BioNTech in oncology trials and recent published results from clinical trials
7
using modRNA influenza vaccines by Moderna, the BNT162 vaccines were expected to
have a favorable safety profile with mild, localized, and transient effects. BNT162 vaccines
based on modRNA have now been administered to humans for the first time in this study and
the BNT162-01 study conducted in Germany by BioNTech, at doses between 1 µg and
100 µg. The currently available safety and immunogenicity data are presented in the BNT162
IB.

2.3. Benefit/Risk Assessment

There is an ongoing global pandemic of COVID-19 with no preventative or therapeutic
options available. While there were no data available from clinical trials on the use of
BNT162 vaccines in humans at the outset of this study, available nonclinical data with these
vaccines, and data from nonclinical studies and clinical trials with the same or related RNA
components, or antigens, supported a favorable risk/benefit profile. Anticipated AEs after
vaccination were expected to be manageable using routine symptom-driven standard of care
as determined by the investigators and, as a result, the profile of these vaccine candidates
supported initiation of this Phase 1/2/3 clinical study.

Updates as part of protocol amendment 6:

• In order for the overall Phase 3 study population to be as representative and
diverse as possible, the inclusion of participants with known chronic stable HIV,
HCV, or HBV infection is permitted. Individuals with chronic viral diseases are at
increased risk for COVID-19 complications and severe disease. In addition, with
the currently available therapies for their treatment, many individuals with chronic
stable HIV, HCV, and HBV infections are unlikely to be at higher safety risk as a

Page 27