BNT162b2 [COMIRNATY (COVID-19 Vaccine, mRNA)] Booster ...

1 BNT162b2 [COMIRNATY (COVID-19 Vaccine, mRNA)] Booster (Third) Dose William C. Gruber, MD, FAAP, FIDSA, FPIDS September 22, 2021. Senior Vice President Vaccine Clinical Research and Development Pfizer Inc CC-1. Data to Support Public Health Need for Booster Data from Israel and the United States suggest vaccine protection against COVID-19. infection wanes approximately 6 to 8 months following the second dose VACCINE EFFICACY WANES. 1 2 3. 3 weeks 6-8 months after D2. Data Source Type Result kaiser Permanente southern Retrospective Reduction in VE is likely due to waning effectiveness rather california (KPSC) Cohort Study than to Delta escaping vaccine protection FDA requested analysis Post-hoc Waning effectiveness over time A Booster dose of BNT162b2 has an acceptable safety profile C4591001 substudy RCT.

2 And elicits robust immune responses Reactogenicity profile similar or better to that seen Israeli Booster vaccination after the second primary series dose RWE. program Restores high levels of protection against COVID-19. outcomes CC-2. Overview of Clinical Program CC-3. BNT162b2 -elicited Sera Effectively Neutralize a Broad Range of SARS-CoV-2 Spike Variants After 2 Doses Viruses are isogenic, recombinant SARS-CoV-2 strains, with variant spike coding sequences on a common, USA-WA1/2020 genetic background 194. LLOD. Circles: 2 weeks PD2. Triangles: 4 weeks PD2. Data from Liu et al., 2021, Nature DOI: ; ; Liu et al., 2021 NEJM, DOI: ;. , Lambda data submitted for publication CC-4.

3 3rd Dose Evaluated in Both Phase 1 and Phase 3. Participants from Original Pivotal Trial Vaccination Follow-up period period Active Surveillance 21 days for Potential COVID-19 symptoms TRIGGER. apart telehealth or in-person visit and nasal swab Vaccination Reactogenicity PHASE 1 Booster . 1 and 2 ~8 months PD2. (N=23). 7 1 6 18. DAYS PD3. AE. SAE. MONTH PD3. Reactogenicity PHASE 3 Booster . ~7 months PD2. (N=312). 7 1 6 18. DAYS PD3. AE. SAE. MONTH PD3. UP TO 2-YEARS through study DEATHS: all participants CC-5. Summary of Data for BNT162b2 Booster (3rd Dose). Administered in C4591001: Phase 1. CC-6. Post-dose 3 BNT162b2 GMTs Indicate a Substantial Boost and Reduced Gap Between WT and Beta Neutralization 18-55 Years Old 65-85 Years Old n=11/group n=12/group GMRBeta/WT (95% CI) ( , ) ( , ) ( , ) ( , ) ( , ) ( , ) ( , ) ( , ) ( , ) ( , ) ( , ) ( , ).

4 2032. 10,000 1202 2119 1567. 50% Serum Neutralizing Titer 1754 1546 1318. 879. 497 538. 147 261. 387. 1,000 150 76. 103. 83. 41. 40. 100 20. LLOD. 10 10 10 10. 10. Before 7 Days 1 Month Before 7 Days 1 Month Before 7 Days 1 Month Before 7 Days 1 Month Dose 1 after after Dose 3 after after Dose 1 after after Dose 3 after after Dose 2 Dose 2 Dose 3 Dose 3 Dose 2 Dose 2 Dose 3 Dose 3. PRNTWT PRNTBeta SARS-CoV-2 Neutralization with BNT162b2 Vaccine Dose 3 | NEJM ( ), DOI: CC-7. Post-dose 3 BNT162b2 GMTs Indicate a Substantial Boost to the Delta Variant Similar to Wild Type 18-55 Years Old 65-85 Years Old n=11/group n=12/group GMRD elta/WT (95% CI) ( , ) ( , ) ( , ) ( , ).

5 1613 1479. 10,000 1546 1321. 50% Serum Neutralizing Titer 1,000 310 196. 241. 123. 100. LLOD. 10. 1 Month After Dose 2 1 Month After Dose 3 1 Month After Dose 2 1 Month After Dose 3. PRNTWT PRNTD elta SARS-CoV-2 Neutralization with BNT162b2 Vaccine Dose 3 | NEJM ( ), DOI: CC-8. Summary of Data for BNT162b2 Booster (3rd Dose). Administered in C4591001: Phase 3. CC-9. Subjects Receiving 3rd Dose were Representative of US. 18-55 Year Olds in Parent Study SAFETY POPULATION. BNT162b2 . N=306. Male 140 ( ). Sex, n (%). Female 166 ( ). White 249 ( ). Black or African American 28 ( ). American Indian or Alaska Native 2 ( ). Race, n (%) Asian 16 ( ).

6 Native Hawaiian or other Pacific Islander 1 ( ). Multiracial 4 ( ). Not reported 6 ( ). Hispanic/Latino 85 ( ). Ethnicity, n (%) Non-Hispanic/non-Latino 219 ( ). Not reported 2 ( ). Comorbiditya Present 174 ( ). Mean (SD) ( ). Age at Booster vaccination (years). Min, Max (19,55). Mean (SD) ( ). Time from Dose 2 to Booster dose (months). Min, Max ( ). a. One or more Charlson comorbidity index, hypertension or obese CC-10. Immunogenicity CC-11. Geometric Mean Ratio of Neutralization Titers Non-inferiority Criterion (Post-dose 3 vs. Post-dose 2) was Met, with Titers ~3-fold Higher Booster Evaluable Immunogenicity Population 1 Month Post Booster 1 Month After 1M Post Booster /1M.

7 (Dose 3) Dose 2 PD2a GMT GMT GMR Met NI. Assay N (95% CI) (95% CI) ( CI) (Y/N). SARS-CoV-2 neutralization ( , 210 ( , ) ( , ) Yes assay - NT50 (titer) ). a. Noninferiority is declared if the lower bound of the confidence interval is > and the point estimate of the GMR is NT50 = 50% neutralizing titers ( Booster Evaluable Immunogenicity Population). CC-12. Noninferiority of Booster Dose Demonstrated Based on Proportion of Subjects with a Seroresponse Seroresponse is defined as achieving a 4-fold rise from baseline (before Dose 1). Booster Evaluable Immunogenicity Population 1 Month Post Booster 1 Month After 1M Post Booster (Dose 3) Dose 2 - 1M PD2a n (%) n (%) %.

8 Assay N (95% CI) (95% CI) ( CI). SARS-CoV-2 neutralization 197 ( ) 194 ( ) 198. assay - NT50 (titer) ( , ) ( , ) ( , ). a. Noninferiority is declared if the lower bound of the 2-sided confidence interval for the percentage difference is greater than -10. If the baseline measurement is below the LLOQ, a postvaccination assay result 4 LLOQ is considered a seroresponse CC-13. Safety CC-14. Follow-up Time for Booster Dose BNT162b2 (30 g). Booster (3rd) Dose N=306. Mean (SD) ( ). Total exposure from Booster Median vaccination to cutoff date (months). Min, Max ( , ). Mean (SD) ( ). Total exposure from Dose 2. Median to cutoff date (months). Min, Max ( , ).

9 Data cutoff date 17 Jun2021. CC-15. Systemic Events by Maximum Severity within 7 Days of 3rd Dose Similar to Post-dose 2 in Parent Study Systematic Events: Mild Moderate Severe Grade 4. Fever: C C C > C. 100% Fever Fatigue Headache Chills Vomiting Diarrhea Muscle Pain Joint Pain 80%. Dose 2 60% (N=2682) 16-55 yrs 40%. (full reacto subset) 20% 0%. BNT162b2 BNT162b2 BNT162b2 BNT162b2 BNT162b2 BNT162b2 BNT162b2 BNT162b2 . (30 g) (30 g) (30 g) (30 g) (30 g) (30 g) (30 g) (30 g). 100%. 80%. Dose 3 60% (N=289) 40% 18-55 yrs 20% 0%. BNT162b2 BNT162b2 BNT162b2 BNT162b2 BNT162b2 BNT162b2 BNT162b2 BNT162b2 . (30 g) (30 g) (30 g) (30 g) (30 g) (30 g) (30 g) (30 g).

10 Fatigue, headache, chills, muscle pain, joint pain severity definition: Mild=no interference; Moderate=some interference; Severe=prevents daily activity; Grade 4=ER visit or hospitalization Vomiting severity definition: Mild=1-2 time in 24h; Moderate=>2 times in 24h; Severe=Requires IV hydration; Grade 4=ER visit or hospitalization Diarrhea severity definition: Mild=2-3 times in 24h; Moderate=4-5 times in 24h; Severe=6 or more times in 24h; Grade 4=ER visit or hospitalization CC-16. Adverse Events by System Organ Class 1% 1 Month Post 3rd Dose Overall Less than Those Post-dose 2 in Parent Studya Safety Population BNT162b2 Post Dose 3 (N=306) BNT162b2 Post Dose 2 (N=12995).