Slide 1: VAX-31 OPUS-1 Pivotal Phase 3 Adult Trial: Topline Results
VAX-31 OPUS-1 Pivotal Phase 3 Adult Trial: Topline Results October 5, 2026
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements related to the potential benefits of Vaxcyte’s carrier-sparing platform and vaccin
Slide 3: Agenda
Agenda INTRODUCTION AND RESULTS OVERVIEW OPUS-1 STUDY AND TOPLINE RESULTS Trial Design, Disposition and Demographics Tolerability and Safety Data Immunogenicity in Adults Aged ≥50 Years and 18-49 Years VAX-31 PROGRAM NEXT STEPS October 5, 2026 3
Slide 4: Introduction and Results Overview
Introduction and Results Overview October 5, 2026 4
Slide 5: Pneumococcal Vaccine Market is Large, Durable and Poised for Significant Growth
Pneumococcal Vaccine Market is Large, Durable and Poised for Significant Growth Combined $8.5B Market Expected to Grow to ~$12B by 2030¹ Driven Primarily by Adult Market Expansion ADULT SEGMENT GROWTH DRIVERS Future Market 2030: ~$12B In 2024, universal recommendation expanded to 1 U.S. adults ≥50 y
Slide 6: VAX-31 is Designed to Offer Comprehensive Coverage to Address Current Gaps
VAX-31 is Designed to Offer Comprehensive Coverage to Address Current Gaps Broadening of Serotype and Disease Coverage Would Eliminate Tradeoffs Required by Current SoC VAX-31 is Designed to Expand Protection Spectrum of Serotype Coverage Drives Adoption in PCVs with Broadest Disease Coverage in Adu
Slide 7: OPUS-1 Inaugurates a More Stringent >0.667 Noninferiority Standard
OPUS-1 Inaugurates a More Stringent >0.667 Noninferiority Standard, Setting a New Bar for Adult PCV Clinical Studies Immune Response Standards for OPA GMRs OPA GMR: LBCI >0.5 LBCI >0.667 LBCI >1 LBCI >2 Historical OPUS-1 Statistically Superiority NI Margin: NI Margin: Greater Margin: Margin: Shared
Slide 8: OPUS-1 Phase 3 Study: Statistical Framework to Define Success
OPUS-1 Phase 3 Study: Statistical Framework to Define Success Co-Primary Immunogenicity Objectives (Adults ≥50): CO-PRIMARY ENDPOINT GROUP 1 CO-PRIMARY ENDPOINT GROUP 2 CO-PRIMARY ENDPOINT GROUP 3 CO-PRIMARY ENDPOINT GROUP 4 11 serotypes shared 9 serotypes shared 8 serotypes shared 3 unique serotype
Slide 9: OPUS-1 Phase 3 Topline Results: VAX-31 Met All Primary Endpoints
OPUS-1 Phase 3 Topline Results: VAX-31 Met All Primary Immunogenicity Endpoints and Safety Objectives Co-Primary Immunogenicity Objectives (Adults ≥50): CO-PRIMARY ENDPOINT GROUP 1 CO-PRIMARY ENDPOINT GROUP 2 CO-PRIMARY ENDPOINT GROUP 3 CO-PRIMARY ENDPOINT GROUP 4 11 serotypes shared 9 serotypes sha
Slide 10: OPUS-1 Study and Topline Results
OPUS-1 Study and Topline Results October 5, 2026 10
Slide 11: Trial Design, Disposition and Demographics
Trial Design, Disposition and Demographics October 5, 2026 11
Slide 12: OPUS-1 Phase 3 Pivotal, Randomized, Double-Blind, Active-Controlled Clinical Trial
OPUS-1 Phase 3 Pivotal, Randomized, Double-Blind, Active-Controlled Clinical Trial in Adults Aged 18 and Older (n=4,047*) Designed to Establish New PCV Standard of Care for Adults Aged 50 and Older Through Head-to-Head Safety, Tolerability and Immunogenicity Comparisons of VAX-31 with PCV20 and PCV2
Slide 13: Study Disposition
Study Disposition ~97% of Vaccinated Subjects Included in Immunogenicity Evaluable Population ≥50 YEARS 18-49 YEARS* Total Enrolled1 Total Enrolled1 N = 3,572 N = 475 Vaccinated: VAX-31 PCV20 PCV21 VAX-31 PCV20 N = 1,194 N = 1,195 N = 1,183 N = 354 N = 120 Included in Safety 100% 100% 100% 100% 100%
Slide 14: Population Demographics in Adults Aged 50 Years and Older
ADULTS ≥50 YEARS Population Demographics in Adults Aged 50 Years and Older Well-Balanced Across Cohorts and Similar for the Safety and Immunogenicity Populations VAX-31 PCV20 PCV21 Safety Immunogenicity Safety Immunogenicity Safety Immunogenicity Number of Subjects 1194 1147 1195 1162 1183 1151 Medi
Slide 15: Population Demographics in Adults Aged 18-49
ADULTS 18-49 YEARS Population Demographics in Adults Aged 18-49 Well-Balanced Across Cohorts and Similar for the Safety and Immunogenicity Populations 18-49 YEARS SAFETY POPULATION VAX-31 RECIPIENTS (IEP) VAX-31 PCV20 18-49 Years 50-64 Years Number of Subjects 354 120 348 763 Median Age, Years (rang
Slide 16: Tolerability and Safety Data
Tolerability and Safety Data October 5, 2026 16
Slide 17: Local and Systemic Solicited AEs in Adults Aged 50 Years and Older
ADULTS ≥50 YEARS Local and Systemic Solicited AEs in Adults Aged 50 Years and Older VAX-31 was Well-Tolerated and Consistent with PCV20 and PCV21, Majority of AEs Resolved Within 48 Hours Grade 1 Grade 2 Grade 3 VAX-31 PCV20 PCV21 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% Pain at Injection Site Redne
Slide 18: Local and Systemic Solicited AEs Similar to PCV20 in Adults Aged 18-49
ADULTS 18-49 YEARS Local and Systemic Solicited AEs Similar to PCV20 in Adults Aged 18-49 VAX-31 was Well-Tolerated and Consistent with PCV20, Majority of AEs Resolved Within 48 Hours Grade 1 Grade 2 Grade 3 VAX-31 PCV20 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% Pain at Injection Site Redness Swellin
Slide 19: Overall Safety Profile Similar to PCV20 and PCV21
Overall Safety Profile Similar to PCV20 and PCV21 50 YEARS AND OLDER SAFETY POPULATION 18-49 YEARS SAFETY POPULATION VAX-31 PCV20 PCV21 VAX-31 PCV20 Number of Subjects 1194 1195 1183 354 120 Unsolicited AE (1-Month), n (%) 75 (6.3) 99 (8.3) 96 (8.1) 37 (10.5) 11 (9.2) Related, n (%) 19 (1.6) 24 (2.0
Slide 20: Immunogenicity Data
Immunogenicity Data In Adults Aged ≥50 Years and 18-49 Years October 5, 2026 20
Slide 21: 11 STs in Common With PCV20 and PCV21
ADULTS ≥50 YEARS 11 STs in Common With PCV20 and PCV21 Met 11 of 11 ST OPA GMR Comparisons Per Prespecified NI Criterion1 (LBCI >0.667) vs PCV20 and/or PCV21 CO-PRIMARY ENDPOINT GROUP 1 VAX-31 vs PCV20 & PCV21 on Common 11 STs 3 6A VAX-31/PCV20 VAX-31/PCV21 7F 8 10A 11A 12F 15B 19A 22F 33F GMR: 1 0.
Slide 22: 9 STs in Common With Only PCV20 and 8 STs Common With Only PCV21
ADULTS ≥50 YEARS 9 STs in Common With Only PCV20 and 8 STs Common With Only PCV21 Met 9 of 9 ST OPA GMR Comparisons vs PCV20 and 8 of 8 vs PCV21 Per Prespecified NI Criterion (LBCI >0.667) CO-PRIMARY ENDPOINT GROUP 2 CO-PRIMARY ENDPOINT GROUP 3 VAX-31 vs PCV20: Shared 9 STs VAX-31 vs PCV21: Shared 8
Slide 23: 3 Unique VAX-31 STs and 20B
ADULTS ≥50 YEARS 3 Unique VAX-31 STs and 20B Met 4 of 4 ST OPA GMR Comparisons Per Prespecified Superiority Criterion (LBCI >2.0) vs PCV20 and/or PCV211 CO-PRIMARY ENDPOINT GROUP 4 VAX-31 vs PCV20 & PCV21: 3 Unique STs + 20B² VAX-31/PCV20 2 VAX-31/PCV21 7C 20C 2 20B GMR: 2 10 60 1 ST = serotype; OPA
Slide 24: Immunobridging Comparison in 18-49-Year-Olds vs 50-64-Year-Olds
ADULTS 18-49 YEARS Immunobridging Comparison in 18-49-Year-Olds vs 50-64-Year-Olds Met Prespecified Primary Endpoint Across All 32 STs¹ (OPA GMR With LBCI >0.667) VAX-31 Immunobridging OPA GMR Comparison (18-49 vs 50-64) 1 15A 2 15B 3 16F 4 17F 5 18C 6A 19A 6B 19F 7C 20C 7F 22F 8 23A 9N 23B 9V 23F 1
Slide 25: Comparator-Specific Assessments: VAX-31 Immune Responses vs PCV20 and PCV21
ADULTS ≥50 YEARS Comparator-Specific Assessments: VAX-31 Immune Responses vs PCV20 and PCV21 VAX-31 Met Noninferiority Criterion for 20/20 STs vs PCV20 and 17/19 STs vs PCV21 VAX-31 vs PCV20: Common 20 STs VAX-31 vs PCV21: Common 19 STs OPA GMRs met prespecified NI criterion OPA GMRs met prespecifie
Slide 26: VAX-31 Data Support Potential Best-in-Class Adult PCV Profile
VAX-31 Data Support Potential Best-in-Class Adult PCV Profile with Broadest Coverage Relative to SoC; Advancing Toward BLA Submission Broad and robust immune responses observed across all 31 STs + 20B for all ages evaluated. Met all prespecified co-primary and immunobridging endpoints. VAX-31 was we
Slide 27: VAX-31 Program Next Steps
VAX-31 Program Next Steps October 5, 2026 27
Slide 28: OPUS Phase 3 Program Serves as Cornerstone of Planned BLA Submission
OPUS Phase 3 Program Serves as Cornerstone of Planned BLA Submission TOPLINE REPORTED ONGOING ONGOING PLANNED OPUS-1 PIVOTAL OPUS-2: OPUS-3: ADULTS MANUFACTURING POTENTIAL VAX-31 TRIAL (N=4,047) CONCOMITANT PREVIOUSLY CONSISTENCY REGULATORY ADMINISTRATION VACCINATED WITH STUDY APPROVAL WITH SEASONAL
Slide 29: Foundation to Support Expected U.S. Commercial Launch
Foundation to Support Expected U.S. Commercial Launch Integrated Manufacturing, Medical and Commercial Execution Commercial Readiness Potential Best-in-Class Profile Manufacturing Execution for U.S. Launch Designed to cover 95% of IPD¹ and Establish commercial manufacturing Medical affairs and comme
Slide 30: Pipeline of Vaccines with Multiple Near-Term Milestones
Pipeline of Vaccines with Multiple Near-Term Milestones Leveraging Cell-Free Platform to Develop Broad-Spectrum Vaccines to Prevent Bacterial Diseases Preclinical Phase 1 Phase 2 Phase 3 Approved Key Milestones Anticipated by End of 2027¹ 31-Valent Adults VAX-31 ADULT INDICATION VAX-31 Infants PCV C
Slide 31: VAXCYTE
VAXCYTE
Slide 32: Appendix
Appendix October 5, 2026 32
Slide 33: VAX-31 Demonstrated Robust OPA GMT Immune Responses
ADULTS ≥50 YEARS VAX-31 Demonstrated Robust OPA GMT Immune Responses OPA GMTs Compared Across VAX-31, PCV20 and PCV21 VAX-31VAX-31 PCV20 PCV21 PCV21 PCV20 10000 OPA GMT (95% CI) 1000 100 10 12F 22F 33F 16F 17F 19F 23F 9V 3 6A 8 9N 31 1 4 5 6B 14 2 7C 7F 10A 11A 15B 19A 15A 23A 23B 35B 18C 20C 20B ST
Slide 34: VAX-31 Demonstrated Robust IgG GMC Responses
ADULTS ≥50 YEARS VAX-31 Demonstrated Robust IgG GMC Responses VAX-31 PCV20 PCV21 VAX-31 100 PCV21 PCV20 IgG GMCs mcg/mL (95% CI) 10 1 0.1 12F 22F 33F 16F 17F 19F 23F 9V 3 6A 8 9N 31 1 4 5 6B 14 2 7C 7F 10A 11A 15B 19A 15A 23A 23B 35B 18C 20C 20B STs COMMON TO VAX-31, PCV20 & PCV21 STs COMMON TO VAX-