Slides
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VAX-24 Infant Phase 2 Dose- Finding Study Topline Results March 31, 2025
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March 31, 2025 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 ability of Vaxcyte’s vaccine candidates and platform to achieve the broadest coverage of any infant pneumococcal conjugate vaccine on the market; the ability for VAX-24 to provide the broadest serotype and disease coverage in infants; the ability of VAX-31 to further expand coverage; precedent criteria for licensure; the timing of the remaining VAX-24 infant Phase 2 study data readout and VAX-31 infant Phase 2 study readouts; the timing of the initiation and data read outs for the VAX-31 adult studies; the ability to deliver a potentially best-in-class pneumococcal conjugate vaccine franchise demand for Vaxcyte’s vaccine candidates; the growth and expansion of the pneumococcal vaccine market; the market opportunity for Vaxcyte’s vaccines; Vaxcyte’s expectations regarding the spectrum coverage and regulatory pathway of its vaccine candidates; and other statements that are not historical fact. The words “anticipate,” “believe,” “continue,” “could,” “designed,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These forward-looking statements are based on Vaxcyte’s current expectations and actual results and timing of events could differ materially from those anticipated in such forward-looking statements as a result of risks and uncertainties, including, without limitation, risks related to Vaxcyte’s product development programs, including development timelines, success and timing of chemistry, manufacturing and controls and related manufacturing activities; potential delays or inability to obtain and maintain required regulatory approvals for its vaccine candidates; the risks and uncertainties inherent with preclinical and clinical development processes; the success, cost and timing of all development activities and clinical trials; and the sufficiency of cash and other funding to support Vaxcyte’s development programs and other operating expenses, any of which could materially and adversely affect Vaxcyte’s business and operations. These and other risks are described more fully in Vaxcyte’s filings with the Securities and Exchange Commission (SEC), including its Annual Report on Form 10-K filed with the SEC on February 25, 2025 or in other documents Vaxcyte subsequently files with or furnishes to the SEC. Vaxcyte undertakes no duty or obligation to update any forward-looking statements contained in this release as a result of new information, future events or changes in its expectations. 2
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March 31, 2025 VAXCYTE MISSION STATEMENT We are on a global mission to engineer high- fidelity vaccines that protect humankind from the consequences of bacterial diseases. 3
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March 31, 2025 Agenda • INTRODUCTION AND VAX-24 INFANT STUDY RESULTS OVERVIEW • VAX-24 INFANT PHASE 2 DOSE-FINDING STUDY TOPLINE RESULTS – Disposition and Demographics – Safety and Tolerability Data – Topline Immunogenicity Data ▪ Post-Dose 3 IgG & Interim OPA ▪ Post-Dose 4 Interim IgG • PLANNING FOR INFANT PHASE 3 PROGRAM • PCV FRANCHISE AND PIPELINE UPDATE 4
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Introduction and VAX-24 Infant Study Results Overview March 31, 2025 5
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VAX-24 Phase 2 Infant Study Results and Platform Demonstrate Potential to Achieve Broadest Coverage of Any Infant PCV On-Market 6March 31, 2025 Topline study results positive and met objectives Safety and tolerability profile similar to standard-of-care VAX-24 elicited substantial IgG, OPA and memory responses and performed particularly well against currently circulating serotypes contained in the vaccine Strong conviction in potential to deliver broadest-spectrum PCVs as we advance into Phase 3 in infants and adults and introduce our third-generation PCV -- VAX-XL Substantial, dose-dependent immune responses and little to no evidence of carrier suppression observed
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March 31, 2025 Over 150,000 U.S. hospitalizations annually due to pneumococcal pneumonia. Globally, Streptococcus pneumoniae is the leading cause of vaccine- preventable deaths in children under five, causing approximately 300,000 deaths each year. Global Health Impact of Pneumococcal Disease (PD) Remains Significant The U.S. CDC lists drug- resistant Streptococcus pneumoniae as a “serious threat.” 7
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8March 31, 2025 14.48% 13.79% 13.10% 9.66% 6.21% 6.21% 4.83% 4.83% 4.14% 3.45% 3.45% 3.45% 1.38% 1.38% 1.38% 1.38% 1.38% 0.69% 0.69% 0.69% 0.69% 0.69% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.69% 0.0% 0.00% 2.00% 4.00% 6.00% 8.00% 10.00% 12.00% 14.00% 16.00% 3 19F 15B/C 22F 15A 33F 23B 11A 35B 10A 23A 38 9N 19A 20 21 33A 18C 16F 35F 4 7F 31 1 2 5 6A/C 6B 7C 8 9V 12F 14 17F 23F Total Coverage (US %)3 47.6% 69.0% 71.7% 91.7% VAX-24 Designed to Provide Broadest Serotype and Disease Coverage in Infants with Opportunity to Further Expand Coverage with VAX-31 Vaxneuvance Prevnar20 VAX-24 VAX-31 1 15C coverage due to cross protection against 15B. 2 The serogroup 20 antigen contained in VAX-24 and VAX-31, formerly known as a 20B variant, has been officially reclassified as 20C. Due to the significant structural homology between 20C and 20B, immune responses elicited by 20C have been demonstratedto be highly cross-reactive with 20B. The Company therefore expects to be able to demonstrate coverage for both serotypes, 20B and 20C, in the anticipated VAX-31 adult Phase 3 studies. Reference: Yu J, et al.; New pneumococcal serotype 20C is a WciG O-acetyltransferase deficient variant of canonical serotype 20B. Microbiol Spectr 0:e02443-24. 3 % of IPD caused in individuals <5 yrs of age in the U.S. in 2023 based on ABC surveillance data References: https://data.cdc.gov/Public-Health-Surveillance/1998-2023-Serotype-Data-for-Invasive-Pneumococcal-/qvzb-qs6p/about_data. 1 2
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VAX-24 Infant Phase 2 Dose-Finding Study Topline Results March 31, 2025 9
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Study Design March 31, 2025 10
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Stage 1: Dose Escalation (n=48*) Stage 2: Main Study (n=789*) VAX-24 Infant Phase 2 Dose-Finding Clinical Study (N=802) Randomize (3:1) Screen VAX-24 1.1 mcg PCV15 DSMB Dose 1 Safety Review at 7 Days VAX-24 2.2mcg PCV15 DSMB VAX-24 2.2mcg/ 4.4mcg PCV15 DSMB Randomize (1:1:1:1) Screen Age 2 months Dose 1 4 months 6 months 7 months 12-15 months 13-16 months 18-21 months Dose 2 Dose 3 Primary Series Immunogenicity Endpoint Dose 4 Boost Immunogenicity Endpoint PCV20 VAX-24 1.1mcg VAX-24 2.2mcg VAX-24 2.2mcg/4.4mcg Age 2 months Dose 1 Safety Review At 7 Days Dose 1 Safety Review at 7 Days Final Safety Assessment March 31, 2025 Randomized, Observer-Blind, Active-Controlled, Dose-Finding, Clinical Study to Evaluate Safety, Tolerability and Immunogenicity of VAX-24 vs. Standard-of-Care (PCV20) in 802 Healthy Infants *The 36 subjects from the three VAX-24 cohorts in Stage 1 proceeded to Stage 2 of the study. The 12 subjects who received PCV15 in Stage 1 were given PCV20 for Doses 2-4 and followed separately and are not included in the safety or immunogenicity evaluable populations. All 36 VAX-24 subjects from Stage 1 proceeded to Stage 2 11
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Identical to Doses Evaluated in VAX-24 Adult Program Three VAX-24 Doses Evaluated in Infant Phase 2 Dose-Finding Study March 31, 2025 3 19F 15B 22F 33F 11A 10A 19A 18C 7F 4 8 6B 12F 9V 14 23F 5 6A 1 9N 20C2 17F 2 4.4 mcg 4.4 mcg 4.4 mcg 4.4 mcg 4.4 mcg 4.4 mcg 4.4 mcg 4.4 mcg Low Dose (1.1mcg) Middle Dose (2.2mcg) Mixed Dose (2.2mcg/ 4.4mcg) PCV20 VAX-24 (2.2mcg) • Mixed dose includes seven serotypes at 4.4mcg strategically chosen based on epidemiological relevance or prior evidence of dose-dependent immune responses to increase the probability of generating non-inferior immune responses for those serotypes. 12 % of IPD in US children <5 yrs of age1 14.5% 13.8% 13.1% 9.7% 6.2% 4.8% 3.5% 1.4% 0.7% 0.7% 0.7% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 1.4% 1.4% 0.0% 0.0% 1 % of IPD caused in individuals <5 yrs of age in the U.S. in 2023 based on ABC surveillance data References: https://data.cdc.gov/Public-Health-Surveillance/1998-2023-Serotype-Data-for-Invasive-Pneumococcal-/qvzb-qs6p/about_data. 2The serogroup 20 antigen contained in VAX-24 and VAX-31, formerly known as a 20B variant, has been officially reclassified as 20C. For additional details on serogroup 20, please see footnote 1 on slide 7.
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Disposition and Demographics March 31, 2025 13
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Study Disposition March 31, 2025 VAX-24 Infant Phase 2 Dose-Finding Study 1Of the 802 randomized subjects, 12 received PCV15 for dose 1 and are not included in the PCV20 vaccinated population and 1 withdrew prior to vaccination. 2 The PD3 immunogenicity population across all cohorts excludes subjects who discontinued from the study or for whom blood samples were unavailable or ineligible. Randomized N = 8021 Included in Safety Population N = 188 Included in Safety Population N = 195 Included in Safety Population N = 201 Included in Safety Population N = 205 Vaccinated PCV20 N = 188 Vaccinated VAX-24 Low Dose N = 205 Vaccinated VAX-24 Mid Dose N = 201 Vaccinated VAX-24 Mixed Dose N = 195 Included in IgG PD3 Immunogenicity Population N = 1512 Included in Interim IgG PD4 Population N = 110 Included in IgG PD3 Immunogenicity Population N = 1522 Included in Interim IgG PD4 Population N = 100 Included in IgG PD3 Immunogenicity Population N = 1422 Included in Interim IgG PD4 Population N = 101 Included in IgG PD3 Immunogenicity Population N = 1292 Included in Interim IgG PD4 Population N = 76 14
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Population Demographics Generally Balanced Across Cohorts March 31, 2025 VAX-24 Low Dose VAX-24 Mid Dose VAX-24 Mixed Dose PCV20 Number of Subjects 205 201 195 188 Median Age, days (Q1, Q3)1 64 ( 61, 68 ) 64 ( 61, 68 ) 64 ( 62, 68) 64 ( 62, 68) Sex, n (%) Female 113 ( 55.1) 103 ( 51.2 ) 94 ( 48.2 ) 87 ( 46.3 ) Male 92 ( 44.9 ) 98 ( 48.8 ) 101 ( 51.8 ) 101 ( 53.7) Race, n (%) White 139 ( 67.8 ) 141 ( 70.1 ) 139 ( 71.3 ) 127 ( 67.6 ) Black 38 ( 18.5 ) 35 ( 17.4 ) 29 ( 14.9 ) 31 ( 16.5 ) Asian 3 ( 1.5 ) 0 ( 0.0 ) 5 ( 2.6 ) 2 ( 1.1 ) Native Hawaiian 0 ( 0.0 ) 0 ( 0.0 ) 0 ( 0.0 ) 0 ( 0.0 ) American Indian or Native Alaskan 1 ( 0.5 ) 1 ( 0.5 ) 2 ( 1.0 ) 1 ( 0.5 ) Other/ Multiracial 24 ( 11.7 ) 24 ( 11.9 ) 20 ( 10.3 ) 27 ( 14.4 ) Median Weight, kg (Q1, Q3) 5.19 ( 4.77, 5.63 ) 5.18 ( 4.73, 5.81 ) 5.29 ( 4.80, 5.72 ) 5.22 ( 4.73, 5.67 ) Median Length, cm (Q1, Q3) 57.66 (55.88 , 59.18) 57.79 (55.88, 59.69) 57.80 (55.88, 59.69) 58.09 (55.88, 59.69) Median Gestational Age, weeks (Q1, Q3) 39 ( 38, 39 ) 39 ( 38, 39 ) 39 ( 38, 39 ) 39 ( 38, 39 ) Median Birth Weight, kg (Q1, Q3) 3.29 ( 2.93, 3.60 ) 3.27 ( 3.00, 3.60 ) 3.27 ( 2.97, 3.63 ) 3.22 ( 2.96, 3.54 ) 1Q1 = First Quartile or 25th Percentile. Q3 = Third Quartile or 75th Percentile. *Four subjects of American Indian race redacted in order to maintain blinding. 15
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Safety and Tolerability Data March 31, 2025 16
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0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Low Mid Mixed PCV20 Low Mid Mixed PCV20 Low Mid Mixed PCV20 Local Solicited AEs Through 7 Days After Each of Three Primary Doses VAX-24 Well Tolerated Across All Dose Cohorts March 31, 2025 ErythemaEdema* Tenderness at Injection Site * One occurrence of severe edema redacted to maintain blinding. Mild Moderate Severe 17
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0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% March 31, 2025 . Fever* Irritability Decreased Appetite Decreased Sleep Increased Sleep Systemic Solicited AEs Through 7 Days After Each of Three Primary Doses VAX-24 Well Tolerated Across All Dose Cohorts * One occurrence of severe fever redacted to maintain blinding. Mild Moderate Severe 18
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0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% PD1 PD2 PD3 PD1 PD2 PD3 PD1 PD2 PD3 PD1 PD2 PD3 Severe Moderate Mild Any Solicited AE Through 7 Days After Each Primary Dose VAX-24 Well Tolerated Across All Dose Cohorts March 31, 2025 VAX-24 MidVAX-24 Low VAX-24 Mixed PCV20 19
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Safety Data from VAX-24 Phase 2 Study Safety Results Similar to PCV20 and Across Cohorts March 31, 2025 VAX-24 Low Dose VAX-24 Mid Dose VAX-24 Mixed Dose PCV20 Overall NUMBER OF SUBJECTS WITH: 205 201 195 188 789 Unsolicited TEAE, n (%) 186 (90.7) 184 (91.5) 181 (92.8) 176 (93.6) 727 (92.1) Related Unsolicited TEAE, n (%) 16 (7.8) 16 (8.0) 17 (8.7) 12 (6.4) 61 (7.7) MAAE, n (%) 178 (86.8) 165 (82.1) 166 (85.1) 158 (84.0) 667 (84.5) Related MAAE, n (%) 3 (1.5) 4 (2.0) 2 (1.0) 2 (1.1) 11 (1.4) NOCI, n (%) 14 (6.8) 12 (6.0) 15 (7.7) 10 (5.3) 51 (6.5) Related NOCI, n (%) * * * * 1 (0.1)1 SAE, n (%) 10 (4.9) 7 (3.5) 11 (5.6) 11 (5.9) 39 (4.9) Related SAE, n (%) 0 0 0 0 0 Death, n (%) 0 0 0 1 (0.1)2 1 (0.1) Related Death, n (%) 0 0 0 0 0 TEAE = Treatment emergent adverse events; NOCI = new onset of chronic illnesses; MAAE = medically attended adverse events; SAE = Serious adverse events. * = Data redacted to maintain blinding until study completion. 1 Related NOCI = mild nasal congestion. 2 One sudden infant death syndrome (SIDS) case occurred in the PCV20 cohort 7 weeks after the first and only dose was administered; following a thorough investigation, case was found to be unrelated to study vaccine. 20
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Topline Immunogenicity Data March 31, 2025 21
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Criteria for Infant Phase 2 Immunogenicity Measures to Support Phase 3 Advancement and Precedent FDA Considerations for Broader-Spectrum Infant PCV Licensure March 31, 2025 • For common STs: Lower limit (LL) of the 95% CI for the difference between the proportion of participants achieving the seroconversion rate (pre-defined IgG concentration ≥0.35 mcg/mL) is > -15%2 for each ST • For unique STs: Achieve same IgG concentration threshold as above, but compared to the ST with the lowest response rate in the comparator PCV, excluding ST3 Primary Series Non-inferiority Post-dose 3 (PD3) or “Prime” • For common STs: IgG GMRs with point estimate of >0.6 for each ST3 • For unique STs: Achieve same IgG GMR threshold as above compared to the ST with lowest IgG GMC in the comparator PCV, excluding ST3 Booster Dose Non-inferiority Post-dose 4 (PD4) or “boost” 22 1 Sources: April 27, 2023 Clinical Review - Prevnar20.pdf and June 17, 2022 Clinical Review (STN 125741/6) – VAXNEUVANCE. 2 Merck applied the >-15% for V114 (Vaxneuvance) Phase 2 endpoint supporting advancement to Phase 3 (https://pmc.ncbi.nlm.nih.gov/articles/PMC7360095/). 3 Based on our statistical analysis of precedent Phase 2 and Phase 3 studies. • IgG antibody levels PD3 (GMR) • Functional antibody levels PD3 and PD4 (OPA) • IgG seroconversion rates PD4 Secondary Immunogenicity Endpoints TOTALITY OF DATA1 Additional Key Considerations • % of circulating disease for each ST • Magnitude of antibody responses • Degree of shortfall on primary endpoints Phase 2 Target • For common STs: FDA has evaluated larger Phase 3 NI registration studies based on achievement of seroconversion rate of > -10% for each ST • For unique STs: Achieve same IgG concentration threshold as above, but compared to the ST with the lowest response rate in the comparator PCV, excluding ST3 • For common STs: FDA has evaluated larger Phase 3 NI registration studies based on LL of the 95% CI for IgG GMR >0.5 for each ST • For unique STs: Achieve same IgG GMR threshold as above compared to the ST with lowest IgG GMC in the comparator PCV, excluding ST3 Phase 3 Endpoints CI = confidence interval; IgG = Immunoglobulin G.
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VAX-24 Demonstrated High Overall Seroconversion Rates Across All Doses March 31, 2025 23 Unique SerotypesSerotypes Common with PCV20 VAX-24 Mixed Dose 3 19F 15B 22F 33F 11A 10A 19A 18C 7F 4 8 6B 12F 9V 14 23F 5 6A 1 9N 20C 17F 2 0 20 40 60 80 100 % of subjects with predefined IgG levels (>0.35mcg/mL) VAX-24 Low Dose PCV20 VAX-24 Mid Dose IgG = Immunoglobulin G. The serogroup 20 antigen contained in VAX-24 and VAX-31, formerly known as a 20B variant, has been officially reclassified as 20C. For additional details on serogroup 20, please see footnote 1 on slide 7.
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March 31, 2025 24 Met Precedent Phase 2 Non-Inferiority Criteria on 20 of 24 STs at All Doses VAX-24 PD3 Seroconversion Rates Compared to PCV20 0.7% 0.7% 1.4% 3.5% 4.8% 6.2% 9.7% 13.1% 13.8% 14.5% 0%5%10%15% 1 6A 5 23F 14 9V 12F 6B 8 4 7F 18C 19A 10A 11A 33F 22F 15B/C 19F 3 -30 -15 0 15 30 45 1 6A 5 23F 14 9V 12F 6B 8 4 7F 18C 19A 10A 11A 33F 22F 15B 19F 3 VAX-24 vs. PCV20: Difference in % of Subjects Meeting Predefined IgG Levels2 -30 -15 0 15 30 45 1 6A 5 23F 14 9V 12F 6B 8 4 7F 18C 19A 10A 11A 33F 22F 15B 19F 3 -30 -15 0 15 30 45 1 6A 5 23F 14 9V 12F 6B 8 4 7F 18C 19A 10A 11A 33F 22F 15B 19F 3 Difference in % of Subjects Meeting Predefined IgG Levels VAX-24 Low Dose (1.1mcg) VAX-24 Mixed Dose (2.2mcg/4.4mcg)VAX-24 Mid Dose (2.2mcg) % of IPD in US children <5 yrs of age1 -30 -15 0 15 30 45 2 17F 20C 9N Difference in % of Subjects Meeting Predefined IgG Levels Difference in % of Subjects Meeting Predefined IgG Levels -30 -15 0 15 30 45 2 17F 20C 9N -30 -15 0 15 30 45 2 17F 20C 9N NI = Non-inferiority; IgG = Immunoglobulin G.. Unique STs0.0% 0.0% 1.4% 1.4% 0%5%10%15% 2 17F 20 9N 0.7% 0% 0% 0% 0% 0% 0% 0% 0% 0% 1 % of IPD caused in individuals <5 yrs of age in the U.S. in 2023 based on ABC surveillance data References: https://data.cdc.gov/Public-Health-Surveillance/1998-2023-Serotype-Data-for-Invasive-Pneumococcal-/qvzb-qs6p/about_data. 2 % of subjects meeting ≥0.35mcg/mL for unique STs were calculated compared to ST 6B, which is the ST in PCV20 with the lowest seroconversion rate Post-Dose 3 (excluding ST 3 or lower responding STs). The serogroup 20 antigen contained in VAX-24 and VAX-31, formerly known as a 20B variant, has been officially reclassified as 20C. For additional details on serogroup 20, please see footnote 1 on slide 7.
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March 31, 2025 25 Met Target Phase 2 Non-Inferiority Criteria for Point Estimate of >0.6 on 22 of 24 STs at Mid and Mixed Doses VAX-24 PD3 IgG GMRs Compared to PCV20 IgG Geometric Mean Ratios for VAX-24 vs. PCV202 0 1 2 3 4 5 6 7 8 9 2 17F 20C 9N 0.0 0.5 1.0 1.5 2.0 2.5 1 6A 5 23F 14 9V 12F 6B 8 4 7F 18C 19A 10A 11A 33F 22F 15B 19F 3 0.0 0.5 1.0 1.5 2.0 2.5 1 6A 5 23F 14 9V 12F 6B 8 4 7F 18C 19A 10A 11A 33F 22F 15B 19F 3 0.0 0.5 1.0 1.5 2.0 2.5 1 6A 5 23F 14 9V 12F 6B 8 4 7F 18C 19A 10A 11A 33F 22F 15B 19F 3 0 1 2 3 4 5 6 7 8 9 2 17F 20C 9N 0 1 2 3 4 5 6 7 8 9 2 17F 20C 9N % of IPD in US children <5 yrs of age1 GMR GMR VAX-24 Low Dose (1.1mcg) VAX-24 Mixed Dose (2.2mcg/4.4mcg)VAX-24 Mid Dose (2.2mcg) = Point Estimate. Unique STs0.0% 0.0% 1.4% 1.4% 0%5%10%15% 2 17F 20 9N 0% 0% 0% 0.7% 0.7% 1.4% 3.5% 4.8% 6.2% 9.7% 13.1% 13.8% 14.5% 0%5%10%15% 1 6A 5 23F 14 9V 12F 6B 8 4 7F 18C 19A 10A 11A 33F 22F 15B/C 19F 3 0% 0% 0% 0% 0% 0% 0% 1 % of IPD caused in individuals <5 yrs of age in the U.S. in 2023 based on ABC surveillance data References: https://data.cdc.gov/Public-Health-Surveillance/1998-2023-Serotype-Data-for-Invasive-Pneumococcal-/qvzb- qs6p/about_data 2GMRs for unique STs were calculated compared to ST 12F, which is the ST in PCV20 with the lowest GMC Post-Dose 3 (excluding ST 3 or lower responding STs). The serogroup 20 antigen contained in VAX-24 and VAX-31, formerly known as a 20B variant, has been officially reclassified as 20C. For additional details on serogroup 20, please see footnote 1 on slide 7
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March 31, 2025 26 Unique SerotypesSerotypes Common with PCV20 3 19F 15B 22F 33F 11A 10A 19A 18C 7F 4 8 6B 12F 9V 14 23F 5 6A 1 9N 20B 17F 2 1 10 100 1000 10000 100000 OPA GMTs (95% CI) VAX-24 Low Dose PCV 20 VAX-24 Mid Dose VAX-24 Mixed Dose VAX-24 PD3 OPA GMT Immune Responses OPA is a Key Secondary Endpoint – GMTs >8 Correlated With Effectiveness Against IPD The serogroup 20 antigen contained in VAX-24 and VAX-31, formerly known as a 20B variant, has been officially reclassified as 20C. For additional details on serogroup 20, please see footnote 1 on slide 7. Serotype 20B was studied in this OPA analysis. IgG = Immunoglobulin G.
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PD4 Interim IgG Immunogenicity Data March 31, 2025 27
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3 19F 15B 22F 33F 11A 10A 19A 18C 7F 4 8 6B 12F 9V 14 23F 5 6A 1 9N 20C 17F 2 0 20 40 60 80 100 % of subjects with predefined IgG Levels (>0.35mcg/mL) VAX-24 Low Dose VAX-24 Mid Dose VAX-24 Mixed Dose PCV20 March 31, 2025 Non-PCV20 SerotypesSerotypes Contained in PCV20 High IgG Seroconversion Rates Across All Doses VAX-24 PD4 Seroconversion Rates 28 The serogroup 20 antigen contained in VAX-24 and VAX-31, formerly known as a 20B variant, has been officially reclassified as 20C. For additional details on serogroup 20, please see footnote 1 on slide 7. IgG = Immunoglobulin G.
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March 31, 2025 29 3 19F 15B 22F 33F 11A 10A 19A 18C 7F 4 8 6B 12F 9V 14 23F 5 6A 1 2 9N 17F 20C 0 5 10 15 IgG GMCs mcg/mLs (95% CI) VAX-24 Mid Dose Post-Dose 3 VAX-24 Mid Dose Post-Dose 4 VAX-24 Demonstrated Robust Memory Responses – PD3 vs PD4 IgG GMCs Non-PCV20 SerotypesSerotypes Contained in PCV20 Robust Booster Responses Elicited at all Doses The serogroup 20 antigen contained in VAX-24 and VAX-31, formerly known as a 20B variant, has been officially reclassified as 20C. For additional details on serogroup 20, please see footnote 1 on slide 7. IgG = Immunoglobulin G.
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March 31, 2025 30 0 1 2 3 4 5 6 7 8 9 2 17F 20C 9N 0.0 0.5 1.0 1.5 2.0 2.5 1 6A 5 23F 14 9V 12F 6B 8 4 7F 18C 19A 10A 11A 33F 22F 15B 19F 3 IgG Geometric Mean Ratios for VAX-24 vs. PCV201 0.0 0.5 1.0 1.5 2.0 2.5 1 6A 5 23F 14 9V 12F 6B 8 4 7F 18C 19A 10A 11A 33F 22F 15B 19F 3 0.0 0.5 1.0 1.5 2.0 2.5 1 6A 5 23F 14 9V 12F 6B 8 4 7F 18C 19A 10A 11A 33F 22F 15B 19F 3 VAX-24 Low Dose (1.1mcg) VAX-24 Mixed Dose (2.2mcg/4.4mcg)VAX-24 Mid Dose (2.2mcg) 0 1 2 3 4 5 6 7 8 9 2 17F 20C 9N 0 1 2 3 4 5 6 7 8 9 2 17F 20C 9N Met Target Phase 2 Non-Inferiority Criteria for Point Estimate of >0.6 on 19 of 24 STs at Mid and Mixed Doses VAX-24 PD4 IgG GMRs GMR GMR Unique STs0.0% 0.0% 1.4% 1.4% 0%5%10%15% 2 17F 20 9N 0.7% 0.7% 1.4% 3.5% 4.8% 6.2% 9.7% 13.1% 13.8% 14.5% 0%5%10%15% 1 6A 5 23F 14 9V 12F 6B 8 4 7F 18C 19A 10A 11A 33F 22F 15B/C 19F 3 0% 0% 0% 0% 0% 0% 0% 0% 0% 0% 1GMRs for unique serotypes were calculated compared to serotype 12F, which is the serotype in PCV20 with the lowest GMC Post-Dose 3 (excluding serotype 3 or lower responding ST). The serogroup 20 antigen contained in VAX-24 and VAX-31, formerly known as a 20B variant, has been officially reclassified as 20C. For additional details on serogroup 20, please see footnote 1 on slide 7.
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Planning for Infant Phase 3 Program March 31, 2025 31
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March 31, 2025 32 VAX-24 Mid Dose (2.2mcg) Selected as Basis for Advancement IgG Geometric Mean Ratios -30 -15 0 15 30 45 1 6A 5 23F 14 9V 12F 6B 8 4 7F 18C 19A 10A 11A 33F 22F 15B 19F 3 PD3 IgG Seroconversion Difference in % of Subjects Meeting Predefined IgG Levels -30 -15 0 15 30 45 2 17F 20C 9N 0.0 0.5 1.0 1.5 2.0 2.5 1 6A 5 23F 14 9V 12F 6B 8 4 7F 18C 19A 10A 11A 33F 22F 15B 19F 3 0 1 2 3 4 5 6 7 8 9 2 17F 20C 9N PD3 IgG GMR 0.0 0.5 1.0 1.5 2.0 2.5 1 6A 5 23F 14 9V 12F 6B 7F 4 8 18C 19A 10A 11A 33F 22F 15B 19F 3 PD4 IgG GMR 0 1 2 3 4 5 6 7 8 9 2 17F 20C 9N IgG Geometric Mean Ratios Pending VAX-31 Phase 2 Topline Data Readout, Prepare for Phase 3 Study With VAX-24 or VAX-31 % of IPD in US children <5 yrs of age Unique STs 0.0% 0.0% 1.4% 1.4% 0%5%10%15% 2 17F 20 9N 0.7% 0.7% 1.4% 3.5% 4.8% 6.2% 9.7% 13.1% 13.8% 14.5% 0%5%10%15% 1 6A 5 23F 14 9V 12F 6B 8 4 7F 18C 19A 10A 11A 33F 22F 15B/C 19F 3 0% 0% 0% 0% 0% 0% 0% 0% 0% 0% The serogroup 20 antigen contained in VAX-24 and VAX-31, formerly known as a 20B variant, has been officially reclassified as 20C. For additional details on serogroup 20, please see footnote 1 on slide 7.
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IgG Responses for STs Dosed at 1.1mcg, 2.2mcg and 4.4mcg* Indicate Opportunity to Increase Dose VAX-24 Dose-Dependent IgG GMR Responses PD3 March 31, 2025 GMR *The 7 STs dosed at 1.1mcg, 2.2mcg and 4.4mcg were 3, 6B, 7F, 9V, 18C, 19A and 19F. 33 0.0 0.5 1.0 1.5 2.0 2.5 19F 19A 18C 9V 7F 6B 3 IgG GMR IgG = Immunoglobulin G. Dose-Dependent Responses Demonstrate Potential for Optimization
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1 4 5 6A 8 10A 11A 12F 14 15B 22F 23F 33F 2 9N 17F 20C 0.1 1 10 IgG GMCs mcg/mLs (95% CI) VAX-24 Mid Dose VAX-24 Mixed Dose IgG Geometric Mean Concentrations 1-month Post-Dose 3 IgG GMCs at Mid and Mixed Doses for 13 STs Dosed at 2.2mcg Absence of Carrier Suppression Observed Indicate Opportunity to Increase Dose March 31, 2025 34 The serogroup 20 antigen contained in VAX-24 and VAX-31, formerly known as a 20B variant, has been officially reclassified as 20C. For additional details on serogroup 20, please see footnote 1 on slide 7.
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35 Adult Data Support Carrier-Sparing Platform Ability to Add Coverage, Adjust Dose and Improve Immune Responses 1 5 22F 2 4 6A 8 9N 10A 11A 12F 14 15B 17F 20B 23F 33F 3 6B 7F 9V 18C 19A 19F 7C 15A 16F 23A 23B 31 35B 0.1 1 10 100 IgG GMC VAX-24 2.2 mcg VAX-31 4.4 mcg VAX-24 2.2 mcg VAX-31 3.3 mcg VAX-24 4.4 mcg VAX-31 3.3 mcg March 31, 2025 High/Mixed Dose IgG GMC Comparison: VAX-24 (50-59) vs VAX-31 (50-59) VAX-31 3.3 mcg Optimized Dose Upward in VAX-31 Optimized Dose Downward in VAX-31 The serogroup 20 antigen contained in VAX-24 and VAX-31, formerly known as a 20B variant, has been officially reclassified as 20C. For additional details on serogroup 20, please see footnote 1 on slide 7. At the time of these studies, the serogroup 20 antigen was classified as 20B. IgG = Immunoglobulin G.
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VAX-24 Phase 2 Infant Study Results and Platform Demonstrate Potential to Achieve Broadest Coverage of Any Infant PCV On-Market 36March 31, 2025 Topline study results positive and met objectives Safety and tolerability profile similar to standard-of-care VAX-24 elicited substantial IgG, OPA and memory responses and performed particularly well against currently circulating serotypes contained in the vaccine Strong conviction in potential to deliver broadest-spectrum PCVs as we advance into Phase 3 in infants and adults and introduce our third-generation PCV -- VAX-XL Substantial, dose-dependent immune responses and little to no evidence of carrier suppression observed
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PCV Franchise and Pipeline Update March 31, 2025 37
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Potential Best-in-Class PCV Franchise for Adult and Infant Segments 38March 31, 2025 24-valent PCV candidate VAX-24 Infants • Announce balance of VAX-24 Phase 2 dose-finding study data, including final safety data, full PD3 OPA data, and full PD4 IgG and OPA data by end of 2025. 31-valent PCV candidate VAX-31 Adults • Following FDA End-of-Phase 2 meeting, initiate Phase 3 pivotal, non-inferiority study by mid-2025 and announce topline safety, tolerability and immunogenicity data in 2026. • Initiate remaining Phase 3 studies in 2025 and 2026 and announce data from these studies in 2026 and 2027. Population Investigational PCV Key Anticipated Milestones (1) Guidance as of March 31, 2025 31-valent PCV candidate VAX-31 • Announce topline safety, tolerability and immunogenicity data for Phase 2 dose-finding study primary three-dose immunization series in mid-2026, with complete booster data up to nine months later. Clinical Development Next Steps and Anticipated Milestones1
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March 31, 2025 $0 $2 $4 $6 $8 $10 $12 $14 2024A ~$13B ~$8B Market Growth Pfizer (Prevnar Family – PCV13 & PCV20) Merck (PCV15, PCV21, PPSV23) GSK (Synflorix) Billions Other 1 Sources: Company websites. 2 Global Pneumococcal Vaccine Market (2022-2027), Infogence Global Research. 3 https://www.cdc.gov/pneumococcal/hcp/vaccine-recommendations/,. 1 PCV MARKET – KEY GROWTH DRIVERS 2027E 2 Global Pneumococcal Vaccine Market PCV Market Growth Expected to Reach ~$13B by 2027 Driven Primarily by Growth in Adult Market Pneumococcal Vaccine Market Poised for Significant Growth • ACIP recently expanded U.S. universal adult vaccination by lowering the age to ≥50 years from ≥65, which significantly expands market • ACIP indicated strong consideration for a potential future shift to a prime-boost schedule to support effective long-term protection in adults • Serotype epidemiology and availability of broader-valency PCVs is leading to additional adult recommendations outside the U.S. • “At risk” adults aged 19-49 years included in U.S. universal PCV vaccination recommendation 3939 Infant segment comprises ~$6B of current global pneumococcal vaccine market
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40 Broad-Spectrum Conjugate and Novel Protein Vaccines to Prevent or Treat Bacterial Infectious Diseases Pipeline of High-Fidelity Vaccines March 31, 2025 Preclinical Phase 1 Phase 2 Phase 3 VAX-31 VAX-A1 VAX- PG 24-Valent PCV Candidate Novel Group A Strep Vaccine Novel Therapeutic Periodontitis Vaccine Adults & Infants Adults VAX-24 31-Valent PCV Candidate Infants VAX-GI Adults & InfantsNovel Shigella Vaccine Adults 50+ Infants VAX-XLVAX-XL PCV Candidate Adults & Infants
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March 31, 2025 Q&A with Management Grant Pickering Chief Executive Officer, Director and Founder Jim Wassil Executive Vice President and Chief Operating Officer Andrew Guggenhime President and Chief Financial Officer 41
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Appendix Slides
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Study Safety, Tolerability and Immunogenicity Key Outcome Measures SAFETY AND TOLERABILITY OUTCOME MEASURES IMMUNOGENICITY OUTCOME MEASURES DAY 7 AFTER EACH DOSE 1 MONTH POST-DOSE 1-4; ONGOING DURING PRIMARY SERIES • Solicited local reactions • Solicited systemic events • Unsolicited adverse events (AE) • % of subjects achieving Immunoglobulin G (IgG) antibody concentration ≥0.35 mcg/mL (seroconversion rate) • IgG Geometric Mean Concentration (GMC) • Opsonophagocytic activity (OPA) Geometric Mean Titer (GMT) 1 MONTH POST- DOSE 3 (PD3)* 1 MONTH POST- DOSE 4 (PD4)* • % of subjects achieving IgG antibody concentration ≥0.35 mcg/mL • IgG GMC and IgG GMC ratio (GMR) • OPA GMT • IgG and OPA Geometric Mean Fold Rise (GMFR) from pre-Dose 4 to 1-month PD4* • % of subjects achieving a 4-fold rise in IgG and OPA from pre-Dose 4 to 1-month PD4* • % of subjects achieving IgG concentration ≥1.0 mcg/mL* 6 MONTHS PD4 • Unsolicited AE • SAE, NOCI and MAAE *Effect on immunogenicity of concomitant vaccination are being evaluated on a subset of subjects PD3 and PD4 based on serum availability. March 31, 2025 • Serious adverse events (SAE), new onset of chronic illnesses (NOCI), medically attended adverse events (MAAE) and treatment emergent AE (TEAE) • SAE, NOCI, MAAE, TEAE 44 *Data for these outcome measures will be available with final data set by end of 2025.