10 COVID Modjarrad 508

CDC ACIP — Vaccine Advisory Committee

Acip

Slides

14

Document text

1 Breakthroughs that change patients’ lives Monovalent XBB.1.5 BNT162b2 COVID-19 Vaccine 
ACIP Presentation September 12, 2023 
CC-2Presentation Outline 
Kayvon Modjarrad, M.D., Ph.D. 
Executive Director, Viral Vaccines 
Vaccine Research and Development, Pfizer Inc. Variant Epidemiology 
COVID-19 Updated Vaccine 
Approval Pathway 
Monovalent XBB.1.5 BNT162b2 
Vaccine Activity Against 
Contemporary Omicron Sublineages 
Clinical Update 

CC-3XBB Sublineages Continue to Dominate the Epidemiolo gic 
Landscape, Despite the Emergence of New Lineages 
Growing Dominance of EG.5.1 
Source: 3D Spike Model - Pfizer 
Mutation Prediction - jbloomlab.github.io/SARS2-RBD-escape-calc Source: GISAID - gisaid.org , data accessed/analyzed in Pizer, September 08, 20 23 
BA.2.86 has high mutational density in Spike 
protein but accounts for <1% of cases 

CC-4Pathway for COVID-19 Variant-Adapted Vaccine Update s 
COVID-19 
Vaccine 
Development Early-stage development 
“at risk” and  
surveillance to inform 
variant selection Manufacture (pre-clinical 
and CMC data), Regulatory 
Submissions and Review Distribute Vaccines Strain Selection FDA Authorization/Approval 
ACIP Recommendation 
• In accordance with FDA guidance for licensure, pre clinical/CMC 
data package submission and review help ensure time ly 
availability of seasonal variant-matched vaccine, s imilar to the 
model for annual influenza vaccine updates. 
CC-5Clinical and Preclinical Experience with Variant-mo dified Vaccines –
Supported Bivalent BA.4/5 Vaccine Authorization 
Preclinical Data Clinical Data Vaccine Regimen Age Group Modified Vaccine Beta monovalent Omicron BA.1 monovalent Omicron BA.1 bivalent Omicron BA.4/5 bivalent 
Ongoing Single Dose 12 to 55 years 
>55 years Omicron XBB.1.5 monovalent 
18 to 55 years 
18 to 55 years 
18 to 55 years 
>55 years 
6 months to 11 years 
12 to 55 years 
>55 years 
Original Vaccine 
 Variant Vaccine 

CC-6Booster Vaccination Study Design 
Female Balb/c mice (10 per group) were experienced with a primary series of monovalent BNT162b2 Origin al vaccine and a 3 rd booster dose of 
bivalent BNT162b2 (Original+BA.4/5) vaccine. Mice t hen received a 4 th booster dose of either a bivalent BNT162b2 (Origina l+BA.4/5) or a monovalent 
BNT162b2 (XBB.1.5) vaccine. 
Data were generated by same pseudovirus neutralizat ion assay and from sera of same mouse study present ed at VRBPAC June 15, 2023 meeting 
(https://www.fda.gov/media/169541/download ). 
Data on file: Pfizer-BioNTech. September 2023. Blood sample 
 Vaccination 
0 21 105 134 Day: 160 
Monovalent 
Original Monovalent 
Original Bivalent 
Original+BA.4/5 Bivalent 
Original+BA.4/5 
Monovalent 
XBB.1.5 

CC-7Monovalent XBB.1.5 BNT162b2 Booster Vaccine Effectiv ely Neutralized 
Predominant and Emerging Variants 
Data were generated by the same pseudovirus neutral ization assay and from sera of same mouse study tha t generated data that were presented at VRBPAC June 15, 2023 Meeting ( https://www.fda.gov/media/169541/download ). 
50% Neutralization Titers are Geometric Mean Titers  of 10 mice per vaccine group. LOD, limit of detect ion; the lowest serum dilution of 1:20. 

CC-8Monovalent XBB.1.5 BNT162b2 Booster Vaccine Elicite d Substantially Higher 
Neutralizing Response Compared to the Bivalent Vacc ine 
Data were generated by same pseudovirus neutralizat ion assay and from sera of same mouse study that ge nerated data that were presented at VRBPAC June 15,  2023 Meeting ( https://www.fda.gov/media/169541/download ). 
GMR = Geometric Mean Ratio of the Geometric Mean Ti ter (GMT) of Monovalent XBB.1.5 divided by GMT of W T+BA.4/5 group.  LOD, limit of detection; the lowes t serum dilution of 1:20. 
/uni0047/uni004D/uni0052/uni0020/uni0028/uni0072/uni0065/uni006C/uni0061/uni0074/uni0069/uni0076/uni0065/uni0020/uni0074/uni006F/uni0020/uni004F/uni0072/uni0069/uni0067/uni0069/uni006E/uni0061/uni006C/uni0020/uni002B/uni0020/uni0042/uni0041/uni002E/uni0034/uni002F/uni0035/uni0029

CC-9Blood sample 
 Vaccination 
0 21 49 Day: 
Bivalent 
(Original/BA.4/5) 
Monovalent 
XBB.1.5 
Bivalent 
(Original/BA.4/5) 
Monovalent 
XBB.1.5 Primary Series Study Design 
Female Balb/c mice (10 per group) were administered  2 doses (21 days apart) of either bivalent BNT162b 2 (Original+BA.4/5) or monovalent 
BNT162b2 (XBB.1.5) vaccine. 
Data were generated by same pseudovirus neutralizat ion assay and from sera of same mouse study present ed at VRBPAC June 15, 2023 meeting 
(https://www.fda.gov/media/169541/download ). 
Data on file: Pfizer-BioNTech. September 2023. 
CC-10These data were generated by same pseudovirus neutr alization assay and from sera of same mouse study t hat generated data that were presented at VRBPAC Jun e 15, 2023 Meeting ( https://www.fda.gov/media/169541/download ). 
50% Neutralization Titers are Geometric Mean Titers  of 10 mice per vaccine group. 
LOD, limit of detection; the lowest serum dilution of 1:20. Monovalent XBB.1.5 BNT162b2 Primary Series Effectiv ely Neutralized 
EG.5.1 and XBB.1.5 

CC-11Monovalent XBB.1.5 BNT162b2 Primary Series Elicited  Substantially Higher 
Neutralizing Response Compared to the Bivalent Vacc ine 
These data were generated by same pseudovirus neutr alization assay and from sera of same mouse study t hat generated data that were presented at VRBPAC Jun e 15, 2023 Meeting ( https://www.fda.gov/media/169541/download ). 
GMR = Geometric Mean Ratio of the Geometric Mean Ti ter (GMT) of Monovalent XBB.1.5 and Bivalent XBB.1. 5+BA.4/5 divided by GMT of WT+BA.4/5 group.  
LOD, limit of detection; the lowest serum dilution of 1:20. 

CC-12Monovalent XBB.1.5 BNT162b2 Clinical Study in Individuals ≥ 12 years 
Monovalent XBB.1.5 BNT162b2 30µg 
Group 1 (n=200): 12- 55 years 
Group 2 (n=200): >55 years 
CC-13• The SARS-CoV-2 epidemiologic landscape remains dom inated by XBB 
sublineages. 
• Monovalent XBB.1.5 BNT162b2 is equally immunogenic  against XBB.1.5, 
EG.5.1 and BA.2.86, in a COVID-19 vaccine-experienc ed preclinical study. 
• Variant-adapted vaccines improve immune responses against antigenically 
matched and closely related strains. 
• A preclinical/CMC package for variant-adapted COVI D-19 vaccine fulfilled 
licensure criteria. Summary 
14 Breakthroughs that change patients’ lives Monovalent XBB.1.5 Pfizer-BioNTech COVID-19 Vaccine 
ACIP September 12, 2023