Slides
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February 24, 2026 Corporate Presentation
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2 Forward-Looking Statements February 24, 2026 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 vaccine candidates, including breadth of coverage and the ability to deliver potentially better immune responses, a potentially best-in-class pneumococcal conjugate vaccine (PCV) franchise and the improvement upon the standard- of-care; demand for Vaxcyte’s vaccine candidates; the design, timing of initiation, progress and expected results of Vaxcyte’s preclinical studies, clinical trials and research and development plans; the ability of Vaxcyte’s cell-free platform to deliver the broadest-spectrum PCVs that provide protection against both currently circulating and historically prevalent strains; applicability of precedent criteria for licensure; Vaxcyte’s ability to establish global commercial manufacturing capacity for its PCV candidates; the ability of Vaxcyte to commercialize its PCV candidates and to meet the PCV franchise market demand for commercial markets; the use and availability of funds from NIH; the growth and expansion of the pneumococcal vaccine market, and the potential to address the need for broader-spectrum of coverage in such market; the market opportunity for Vaxcyte’s vaccines; Vaxcyte’s expectations regarding the potential benefits, spectrum coverage, clinical or regulatory pathways, adoption speed and immunogenicity 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 sufficiency of cash and other funding to support Vaxcyte’s development programs and other operating expenses. 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 24, 2026 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.
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3February 24, 2026 VAXCYTE MISSION STATEMENT We are on a global mission to engineer high- fidelity vaccines that protect humankind from the consequences of bacterial diseases.
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Highlights: Potential Best-in-Class Pneumococcal Conjugate Vaccine (PCV) Franchise 4February 24, 2026 VAX-31 OPUS-1 Phase 3, Noninferiority Trial Designed to Establish Fulsome Coverage for Adults is Underway OPUS = OPA-based Pivotal U.S. study, BTD = Breakthrough Therapy designation, IPD = invasive pneumococcal disease, MOA = mechanism of action. (1) Guidance as of February 24, 2026. The VAX-A1 Phase 1 adult clinical study has the primary objective of assessing safety and tolerability and will be conducted in Australia. (2) Reflects cash, cash equivalents and investments at December 31, 2025 of ~$2.4B, and estimated net proceeds from February 2026 follow-on offering of ~$600.2M. • Carrier-sparing, site-specific conjugation platform enabling broader-spectrum PCVs • Adult Indication: – VAX-31: Broadest-spectrum PCV in the clinic – Enrollment underway in three Phase 3 studies, including pivotal, noninferiority trial (OPUS-1) – FDA BTD granted for IPD and pneumonia – Designed to cover ~95% of IPD while maintaining pressure on currently circulating and historically disease-causing serotypes in U.S. adults ≥ 50 years of age • Pediatric Indication: – VAX-24: Announced final data from positive infant Phase 2 dose-finding study – VAX-31: Enrollment completed in Phase 2 dose-finding study, which includes multiple higher doses designed to optimize immune responses in children • VAX-XL: Third-generation PCV to further expand coverage • Strategic Manufacturing Approach – Building out capacity to satisfy global PCV demand for developed markets – Global commercial manufacturing agreement with Lonza to produce key PCV components – Agreement with Thermo Fisher Scientific to establish U.S. fill-finish manufacturing; expands domestic capacity to support future commercial manufacturing • Seasoned management team, directors and advisors • Pro forma cash, cash equivalents and investments of ~$3.0B² POTENTIAL BEST-IN-CLASS PCV FRANCHISE HIGHLY ATTRACTIVE PCV MARKET ALIGNED CRITICAL RESOURCES • Vaxcyte PCV Franchise – Leverages site-specific conjugation to expose protective T-cell antigens – Enables carrier-sparing conjugates that honor well-understood PCV MOA • Permits production of “tough-to-make” antigens • Platform unlocks large market opportunities beyond PCVs, including Group A Strep and Shigella • VAX-A1: Novel Group A Strep vaccine – Plan to initiate Phase 1 adult study in 2026¹ • VAX-GI: Novel Shigella vaccine EXCLUSIVE CELL-FREE PLATFORM • Well-defined ~$8B market segment poised for substantial growth – Age range in U.S. recently expanded to include adults ≥ 50 years of age; and – Many developed countries now adopting universal vaccination of older adults • Leverages established surrogate immune endpoints as basis for full approval, negating need for field efficacy studies to support licensure • Serotype and disease spectrum of coverage is the primary adoption driver, yet incumbents limited to partial coverage, which is driven by carrier suppression
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SPEED, FLEXIBILITY , SCALABILITY • Rapidly screen vaccine candidates • Flexible reaction conditions • Large-scale production achieved using standard equipment SUPERIOR CONJUGATE VACCINES • Site-specifically attach antigens onto protein carriers designed to: – Enable consistent exposure of T-cell epitopes and/or B-cell epitopes on protein carrier – Avoid off-target effects – Enable use of less protein carrier without sacrificing immunogenicity – Enable broader-spectrum vaccines NOVEL PROTEIN VACCINES • Able to produce “tough- to-make” protein antigens that conform to target pathogens • Increased likelihood of protective immune response 5 • Transcriptional & translational (ribosomal) protein production machinery from E. coli • Produces singular protein of interest at high yields • Enables site-specific conjugation via insertion of multiple nnAA conjugation anchors • Permits protein production in non-physiological conditions Facilitates Design and Production of Proteins Beyond the Reach of Conventional Methods Cell-Free Protein Synthesis Platform Unlocks Multiple Vaccine Applications February 24, 2026 VAXCYTE CELL-FREE PROTEIN SYNTHESIS PLATFORM: XpressCF
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• Announce safety, tolerability and immunogenicity data from the: ̶ OPUS-1 Phase 3 pivotal, noninferiority trial in the fourth quarter of 2026 (topline data) ̶ OPUS-2 and OPUS-3 trials in the first half of 2027² 6 Pipeline of High-Fidelity Vaccines with Multiple Near-Term Milestones February 24, 2026 (1) Guidance as of February 24, 2026. (2) OPUS-2 is a Phase 3 trial evaluating concomitant administration of VAX-31 with a seasonal influenza vaccine; OPUS-3 is a Phase 3 trial evaluating VAX-31 in adults who have previously received pneumococcal vaccination. Broad-Spectrum Conjugate and Novel Protein Vaccines to Prevent Bacterial Infectious Diseases Preclinical Phase 1 Phase 2 Phase 3 Novel Group A Strep Vaccine Adults & Infants 24-Valent PCV Candidate Infants Adults & InfantsNovel Shigella Vaccine 31-Valent PCV Candidate Adults Infants Third-Generation PCV Candidate Adults & Infants Approved VAX-A1 VAX-24 VAX-GI VAX-31 VAX-XL Anticipated 2026 and 2027 Key Milestones¹ • Announce topline data from the ongoing Phase 2 dose-finding study from both the primary three-dose immunization series and booster dose either sequentially or together by the end of first half of 2027 VAX-31 ADULT INDICATION VAX-31 INFANT INDICATION • Initiate Phase 1 adult clinical study in 2026, with the primary objective of assessing safety and tolerability VAX-A1
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7 Grant Pickering, MBA Chief Executive Officer & Co-Founder Jim Wassil, MS, MBA Executive VP & Chief Operating Officer February 24, 2026 Experienced Management Team with Track Record in Vaccines and Biopharma Harp Dhaliwal, MBA Chief Technology Officer Andrew Guggenhime, MBA President & Chief Financial Officer Roger Nosal Head of Global Regulatory & Quality Jeff Fairman, PhD VP Research & Co-Founder Chris Griffith, MS, MBA Chief Business & Strategy Officer Mike Mullette, MBA Chief Commercial Officer
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PCV Opportunity
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February 24, 2026 9 A Global Health Impact of Pneumococcal Disease Remains Significant Global pneumococcal disease in children is driven by emerging serotypes not covered by currently available vaccines and in adults by not only emerging serotypes, but also fragmented coverage of today’s standard of care vaccines • Streptococcus pneumoniae is the leading cause of vaccine-preventable deaths globally in children under five⁴ • ~225K U.S. adult hospitalizations annually caused by pneumococcal pneumonia⁵ • ~300K children under five years old die annually worldwide due to Streptococcus pneumoniae⁶ Vaccinations are recommended globally for infants and adults to prevent PD1,2 • >170 countries have officially introduced PCVs into national immunization programs³ • Routine SoC schedule in the U.S.: – Infants: ▪ Prevnar 20® (PCV20) x 4 doses; or ▪ Vaxneuvance® (PCV15) x 4 doses – Adults aged 50 and older (single dose): ▪ PCV20 or Capvaxive (PCV21); or ▪ PCV15 & Pneumovax® 23 (PPV23) ABOUT STREPTOCOCCUS PNEUMONIAE GLOBAL INCIDENCE & IMPACT OF PD STILL SUBSTANTIAL CURRENT ~$8 BILLION GLOBAL VACCINE CATEGORY Streptococcus pneumoniae is the most common pathogen causing pneumococcal disease (PD) • Non-invasive PD includes otitis media, sinusitis, pneumonia • Invasive PD (IPD) includes bacteremia, meningitis • Pneumococci cause over 50% of bacterial meningitis cases in the U.S. SoC = standard of care. (1) https://www.cdc.gov/pneumococcal/hcp/vaccine-recommendations/. (2) https://www.cdc.gov/pinkbook/hcp/table-of-contents/chapter-17-pneumococcal-disease.html. (3) https://view-hub.org/vaccine/pcv, accessed source December 2025. (4) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8677503/table/T2/. (5) https://www.cdc.gov/mmwr/volumes/74/wr/mm7401a1.htm. (6) https://www.cdc.gov/pneumococcal/php/surveillance/index.html#:~:text=Global%20trends,deaths%20occur%20in%20developing%20countries.
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10 Non-Vaccine Serotypes Increase in Prevalence, as Circulation of Vaccine Serotypes is Eliminated, Resulting in the Need for Broader-Spectrum Vaccines February 24, 2026 Serotype Replacement Drives Need for Broader-Spectrum Vaccines (1) Ladhani et al, Lancet Infect Dis 2018 Apr;18(4):441-45 inclusive of unpublished raw data. UK IPD CASES IN ADULTS > 651 0 5 10 15 20 25 30 2000 2005 2010 2015 Cases Per 100,000 Prevnar 13 Types Non-vaccine Types Residual disease driven by incremental 11 strains over and above PCV13. PCV13 highly effective in prevention of IPD and circulation of included strains.
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11February 24, 2026 Coverage Expansion Needed to Address Circulating Disease, but Protein Carrier Backbone Problematic Limitations of Current PCVs Sources: Prevnar 7, Prevnar 13, Prevnar 20, Vaxneuvance and Capvaxive product inserts. LIMITATIONS OF CONVENTIONAL CHEMISTRY • Random conjugation masks on-target T-cell epitopes on the protein carrier • Conventional reductive amination chemistry requires higher amounts of protein carrier than polysaccharide to form stable conjugates • Overabundance of protein carrier exacerbates carrier suppression, due to competition for CD4+ help between disease-specific polysaccharides and non- disease specific protein carrier PROTEIN CARRIER DIVERTS IMMUNE RESPONSE 20 34 51 65 16 31 46 84 0 10 20 30 40 50 60 70 80 90 Prevnar 7 Prevnar 13 Prevnar 20 Capvaxive Protein Carrier (mcg) Discrete Pneumococcal Polysaccharides (ug)
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(1) Immunoglobulin G (IgG) Geometric Mean Concentrations post-dose 4 – Prevnar 20 BLA Clinical Review Memorandum by FDA (STN: 125731/189). April 27, 2023. (2) Prevnar 20 BLA Clinical Review Memorandum. STN: 125731/0 June 8, 2021. OPA = opsonophagocytic assay. GMR = geometric mean ratio. Diminished immune response to target polysaccharides due to cumulative amount of protein carrier • Expanded spectrum of coverage requires increasing protein carrier burden • Reduced immune responses consistently demonstrated with > spectrum PCVs in both infants and adults February 24, 2026 Coverage Expansion Using Conventional Chemistry Has Led to Carrier-Induced Immune Suppression Limitations of Current PCVs: Adding Conjugates Results in Lower Ab Titers ADULT IMMUNE RESPONSES (OPA): PCV20 VS PCV132 INFANT IMMUNE RESPONSES (IgG): PCV20 VS PCV131 CARRIER SUPPRESSION 12 0.0 0.5 1.0 1.5 23F 19F 19A 18C 14 9V 7F 6B 6A 5 4 3 1 0.0 0.5 1.0 1.5 23F 19F 19A 18C 14 9V 7F 6B 6A 5 4 3 1 GMR GMR
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13 eCRM: Enhanced Potency Potential • Avoids masking sites on CRM197 carrier responsible for T-cell help • Optimized sites for conjugation using copper-free click chemistry • More consistent antigenic presentation Carrier-Sparing Conjugates • Less protein carrier / conjugate may allow addition of more serotypes while minimizing carrier suppression and maintaining immunogenicity • VAX-31 and VAX-24 conjugates form standard PCV interstrand crosslinked matrices – Perceived as foreign by the host – Allows use of standard critical quality attributes and serological assays February 24, 2026 Cell-Free Platform Enables Precise Conjugation to Enhance Potency of Standard Protein Carrier Vaxcyte’s PCV Franchise Employs Carrier-Sparing Conjugates PROPRIETARY eCRM® PROTEIN CARRIER WITH PRECISE, SITE-SPECIFIC CONJUGATION SITES VAXCYTE CARRIER-SPARING CONJUGATES MIMIC THE CUSTOMARY MATRIX FORM Illustrative nnAA Conjugation Anchors (red) Avoid T-cell Epitope Regions (pink)
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February 24, 2026 14 Utilizes Proven Components, Chemistries and Assays to Reduce Risk and Uncertainty Vaxcyte PCV Franchise Design Leverages Many Standard PCV Conventions CDAP / Periodate Activation Pfizer/Merck Methods Amination for Labeling PS Incorporation of Non-natural AAs Site-Specific Click Chemistry Conjugation Vaxcyte CQA Release Assays (Mol Wt, Free PS) Serological Assays (IgG & OPA) Random Lysine Conjugation Novel Enablement: Site-specific conjugation via incorporation of nnAA conjugation anchors Polysaccharide Protein Carrier Assays
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February 24, 2026 15 Pneumococcal Vaccines Represent One of the Largest Segments of Global Vaccine Market, with Significant Growth Expected¹ Vaxcyte’s PCV Franchise Has More Fulsome Coverage Versus On-Market PCVs 4 6B 9V 14 18C 19F 23F 1 5 7F 3 6A 19A 22F 33F 8 10A 11A 12F 15B/C 2 9N 17F 20² 7C 15A 16F 23A 23B 31 35B 24F SoC = standard of care. Source: Prescribing information for Prevnar, Prevnar 13, Prevnar20, Synflorix, Vaxneuvance, Prevnar 20 and Capvaxive. Company filings for Vaxcyte. Capvaxive is approved for use in adults only. (1) Public Company Reports: PFE, MRK, SNY, MRNA, GSK, AZN, excluding Covid-19 vaccine sales. (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 demonstrated to be highly cross-reactive with 20B. The Company therefore expects to be able to demonstrate coverage for both serotypes, 20B and 20C, in the VAX-31 adult Phase 3 and infant Phase 2 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. Within the serotype 20 group, strain 20B is the predominant circulating strain and shows greater genetic similarity to 20C compared to 20A. PCV21 includes 20A, VAX-31 includes 20C, with 20B planned to be evaluated in clinical studies to demonstrate cross protection. VAX-31 VAX-24: 24-valent PCV designed to cover more serotypes than any pediatric pneumococcal vaccine on-market today VAX-31: 31-valent PCV, the broadest-spectrum PCV in the clinic, designed to cover both currently circulating and long-established, historically disease-causing serotypes VAX-24
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16February 24, 2026 Vaxcyte’s PCV Franchise Has the Potential to Be Best-in-Class Due to Broader Coverage and Improved Immunogenicity Pneumococcal Vaccine Market is Highly Attractive PCVs ARE HIGHLY EFFECTIVE • Well-understood T-cell dependent MOA tied to co-presentation of disease-specific polysaccharide antigens with T-cell epitopes on protein carrier to drive durable and boostable immune responses • Well-defined clinical development path with surrogate immune endpoints as basis for full approval, negating need for field efficacy trials COVERAGE & RECOMMENDING BODIES DRIVE ADOPTION • Potential for rapid adoption, with spectrum of coverage and ACIP recommendation driving uptake • Examples: • Shingrix® vs Zostavax® • Gardasil® vs Cervarix® • PCV20 vs PCV15 DURABLE & RAPID REVENUE • Prevnar Family (PCV7/PCV13/PCV20) & PPSV23 have generated >$100B in revenues • PCV13 and PCV20 had combined annual sales of ~$6.5B in 2025 • PCV21 generated $759M in 2025 (launched 3Q 2024) ATTRACTIVE MARGINS • Pneumococcal vaccines are premium priced, delivering highly attractive margins • Broader-spectrum PCVs extend premium price in the U.S.1 • PCV21: $302 (adult) • PCV20: $275 • PCV15: $241 (pediatric) PNEUMOCOCCAL VACCINE MARKET DYNAMICS • Broader-spectrum of serotype and disease coverage drove 98% adoption for PCV20 over PCV15 despite ACIP recommendation of both vaccines MOA = mechanism of action; ACIP = U.S. CDC Advisory Committee on Immunization Practices; PPSV23 = Pneumovax 23. (1) Private Sector costs per dose of the Current CDC Vaccine Price List, VFC Program; source link. (2) FDA safety assessment of PCV20 data presented at February 2024 ACIP meeting. 2% 98% SEROTYPE & DISEASE COVERAGE ADVANTAGE IS PRIMARY DRIVER OF U.S. PCV MARKET ADOPTION PCV15 PCV20 PCV VACCINATION IN ADULTS AGED ≥ 65 JULY 2021 - NOVEMBER 20232
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PCV recommendation expanded to U.S. adults 50+ (from 65+)¹ “At risk” adults aged 19-49 included in U.S. recommendation Potential shift to adult prime- boost schedule in U.S. Expanded OUS adult PCV recommendations Combined Total Market Today: ~$8B Pediatric Market Highly Penetrated; Significant Growth Opportunity in Adult Segment EXPECTED ADULT SEGM ENT GROW TH DRIVERS 17February 24, 2026 (1) https://www.cdc.gov/pneumococcal/hcp/vaccine-recommendations/. $8B Market With Expected Growth Driven Primarily by Adult Market Expansion Pneumococcal Vaccine Market Poised for Significant Growth
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Recent Burst of Adult PCV Recommendations Outside the U.S. Serotype Epidemiology, Broad-Valency PCVs Driving New Recommendations and Shift from PPSV23 to PCVs PPSV23 = Pneumovax 23. (1) Transition from PPSV23 to PCV-only or newly introduced PCV recommendation: France, Germany, Japan, Netherlands, Spain (regional, Galicia), Switzerland, United Kingdom. (2) Pfizer 3Q25 earnings reporting, 3Q24 to 3Q25; Prevnar family includes revenues from Prevnar 20/Prevenar 20 (pediatric and adult) and Prevnar 13/Prevenar 13 (pediatric and adult). Licensure of broader-spectrum PCVs is driving adult universal recommendations internationally Expanded Global Adult PCV Adoption P C Vs NOW RECOMMENDED¹ Japan Switzerland Spain (Regional) PRIOR ADULT RECOMMENDATION: Netherlands France Germany United Kingdom No Prior Universal, Age-Based PCV Recommendation or PPSV23 Only February 24, 2026 18 International revenues for the Prevnar vaccine family increased 17% year-over-year² e Prevnar vaccine family increased 17% year-over- year²
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Establishing Manufacturing Capacity, Robust Supply Chain to Support Expected VAX-31 Adult U.S. Launch, Followed by U.S. Infant and Global Adult and Infant PCV Launches February 24, 2026 19 U.S. Fill-Finish Manufacturing Agreement with Thermo Fisher Global Commercial Manufacturing Agreement with Lonza • Relationship encompasses production of key PCV components • Dedicated large-scale facility built to provide capacity for U.S. and global demand for adults and infants • Agreement expands domestic capacity (North Carolina) • Supports future commercial manufacturing and deepens investment in American innovation and infrastructure
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New slide/format VAX-31 Adult Clinical Program
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21February 24, 2026 VAX-31 Designed to Expand Protection with Broadest Disease Coverage in Adults Percentage of IPD and Non-Bacteremic Pneumococcal Pneumonia Covered by PCVs in U.S. Adults IPD1 ≥50 years Pneumococcal Pneumonia2 ≥50 years All estimates assume cross-protection between serotypes 6A and 6C and between 15B and 15C. (1) CDC 2023 Active Bacterial Core (ABC) Surveillance data; IPD cases with missing serotype data were excluded, non-typeable cases were included in the denominator. (2) King LM et al. Pneumococcal Serotype Distribution and Coverage of Existing and Pipeline Pneumococcal Vaccines, The Journal of Infectious Diseases, 2025, jiaf376; https://doi.org/10.1093/infdis/jiaf376; the percentage covered by PCV is based on a weighted average based on inpatient pneumonia cases (50–64 years of age, ≥65 years of age). 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% PCV15 PCV20 PCV21 VAX-31 47% 61% 81% 95% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% PCV15 PCV20 PCV21 VAX-31 88% 44% 57% 69%
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February 24, 2026 22 Next Generation PCV Designed to Cover ~95% of IPD and ~88% of Pneumococcal Pneumonia in U.S. Adults Aged 50+ with Potential to Provide an Incremental 14-34% Broader IPD Coverage and 19-31% Broader Pneumonia Coverage than Standard-of-Care Vaccines VAX-31 is Designed to Provide Comprehensive Coverage, While Maintaining or Improving Immune Responses, Relative to Today’s SoC that Only Provides Partial Coverage 4 6B 9V 14 18C 19F 23F 1 5 7F 3 6A/C² 19A 22F 33F 8 10A 11A 12F 15B/C² 9N 17F 201 15A 16F 23A 23B 31 35B 2 7C 24F Total Coverage3 4.4 mcg 4.4 mcg 4.4 mcg 95% 4.4 mcg 61% 81% % of IPD in U.S. adults >50 yrs of age³ SoC = standard of care. (1) Serotype 20 comprises closely related subtypes for which cross-protection is assumed. Within the serotype 20 group, strain 20B is the predominant circulating strain and shows greater genetic similarity to 20C compared to 20A. PCV21 includes 20A, VAX-31 includes 20C, with 20B planned to be evaluated in clinical studies to demonstrate cross protection. The serogroup 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 2 on slide 15. (2) Serotypes 6A/6C and 15B/15C are closely related subtypes for which cross-protection is assumed. PCV21 includes 15C, PCV20 and VAX-31 include 15B, and all three—PCV21, PCV20, and VAX-31— include 6A. (3) % of IPD caused in individuals ≥50 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. PCV20 (2.2mcg) PCV21 (4.0mcg) 6.4% 0.0% 0.2% 0.1% 0.1% 4.9% 0.1% 0.0% 0.0% 0.5% 18.8% 1.9% 1.6% 10.6% 2.3% 2.3% 1.4% 3.9% 3.4% 2.9% 5.6% 1.0% 4.8% 4.0% 3.0% 5.4% 2.5% 1.8% 3.7% 0.0% 2.0% 0.0% VAX-31 (3.3mcg)
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VAX-31 Adult Phase 3 Program 23February 24, 2026
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Announce Data³: 1H 2027 Studies Enrolling Subjects and Designed to Support Potential BLA Filing (Combined Subject Enrollment: n~6,000) VAX-31 OPUS Phase 3 Adult Program Overview February 24, 2026 2026 2027 ANTICIPATED TIMING²VAX-31 PHASE 3 STUDIES¹ 2025 OPUS-2: Concomitant Administration with Seasonal Influenza Vaccine ~1,300 healthy pneumococcal-naïve adults aged 50 or older OPUS-3: Adults Previously Vaccinated with Pneumococcal Vaccines ~720 healthy adults aged 50 or older with a history of prior pneumococcal vaccination Enrollment Underway BLA = Biologics License Application. (1) Also planning for a manufacturing consistency study (e.g., a lot-to-lot study). (2) Guidance as of February 24, 2026. (3) Includes safety, tolerability and immunogenicity data. Enrollment Underway 24 OPUS-1: Pivotal, Noninferiority Trial ~3,560 healthy adults aged 50 or older & ~440 adults aged 18-49 Announce Topline Data³: Q4 2026 Enrollment Underway Announce Data³: 1H 2027
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Key primary immunogenicity objectives: • Noninferiority2 of VAX-31 compared with PCV21 and/or PCV20 for the 28 serotypes shared with one or both comparators • Superiority3 for the three serotypes unique to VAX- 31 and serotype 20B versus the comparator vaccines OPUS-1 Phase 3 Noninferiority Trial Evaluating VAX-31 for the Prevention of Invasive Pneumococcal Disease and Pneumonia in Adults (n~4,000) February 24, 2026 ADULTS AGED ≥50 YEARS (N~3,560) Key primary immunogenicity objective: • Noninferiority of VAX-31 immune responses in adults 18-49 years of age compared to those in adults 50-64 years of age ADULTS AGED 18–49 YEARS (N~440) 25 Screen PCV20: n~1,187 VAX-31: n~1,187 Standard 6 Month Safety Follow-Up Blood Sample OPA VAX-31 vs PCV21 and/or PCV20⁴ Control Group: PCV20: n~110 Randomize (1:1:1) PCV21: n~1,187 Screen Randomize (3:1) Month 1 Month 6 VAX-31: n~330 Day 1 OPA VAX-31 Age Group Comparison 18-49 vs 50-64⁴ Blood Sample Dose Study Designed to Establish New Standard for Adult PCVs Through Head-to-Head Safety, Tolerability and Immunogenicity Comparisons of VAX-311 with PCV21 and PCV20, the Current Standards of Care in U.S. Adults OPA = opsonophagocytic activity. (1) VAX-31 High Dose (all serotypes dosed at 3.3mcg, except serotypes 1, 5, and 22F which are dosed at 4.4mcg) selected to advance to Phase 3. (2) Primary Noninferiority Objective: The lower bound of the two-sided 95% confidence interval (CI) for the OPA geometric mean ratio (GMR) of VAX-31 exceeds 0.667. (3) Primary Superiority Objective: The lower bound of the two-sided 95% CI of the OPA GMR exceeds 2.0. (4) IgG comparisons of VAX-31 versus PCV21 and/or PCV20 are secondary endpoints.
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>0.667 >2.0 >0.667 February 24, 2026 26 Expected to Serve as Cornerstone of BLA Package for Potential Licensure in Adults OPUS-1 Phase 3 Pivotal Noninferiority Trial Key Objectives KEY SAFETY & TOLERABILITY OBJECTIVES • Safety and tolerability will be evaluated for 6 months following initial vaccination, including SAE, NOCI, and MAAE; Day 1 to Day 7, solicited local reactions and solicited systemic events will be evaluated; Day 1 to Month 1, all unsolicited AEs will be evaluated SAE = serious adverse events, NOCI = new onset of chronic illnesses, MAAE = medically attended adverse events, AE = adverse events, BLA = Biologics License Application. SECONDARY OBJECTIVES • Noninferiority compared with PCV21 and/or PCV20 for the 28 serotypes (STs) shared with either or both comparator vaccines in adults 50+ • Superiority of VAX-31 compared with PCV21 or PCV20 for the 3 STs unique to VAX-31 (2, 7C and 20C) and for ST 20B in adults 50+ • Noninferiority of immune responses in adults aged 18-49 years compared with those in adults aged 50-64 years VAX-31 IMMUNOGENICITY STUDY OBJECTIVES • Noninferiority compared with both PCV21 and PCV20 for the 11 STs common to all three vaccines in adults 50+ • Statistically greater immune responses relative to PCV21 or PCV20 for the 28 shared STs in adults 50+ • Superiority compared with PCV20 for the 8 STs common to VAX-31 and PCV21 but not included in PCV20 in adults 50+ • Superiority compared with PCV21 for the 9 STs common to VAX-31 and PCV20 but not included in PCV21 in adults 50+ OPA GMR LOWER BOUND OF TWO-SIDED 95% CONFIDENCE INTERVAL >0.5 >1.0 >2.0 >2.0 OPA GMR LOWER BOUND OF TWO-SIDED 95% CONFIDENCE INTERVAL PRIMARY OBJECTIVES EVALUATION CRITERIA Key additional considerations included in totality of data for potential BLA: Results from additional VAX-31 Ph 3 studies, magnitude of Ab responses, degree of shortfall on primary endpoints for any STs that do not hit noninferiority threshold, % of circulating disease for each ST, % of incremental disease coverage of unique STs.
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GMR: 0.0 0.5 1.0 1.5 2.0 2.5 33F 23F 22F 19F 19A 18C 15B 14 12F 11A 10A 9V 8 7F 6B 6A 5 4 3 1 27 OPA GMR Responses for VAX-31 (Phase 2) and PCV21 (Phase 3) vs PCV20 (1) CI LL >1.0. (2) Source: package insert Capvaxive. 0.0 0.5 1.0 1.5 2.0 2.5 33F 23F 22F 19F 19A 18C 15B 14 12F 11A 10A 9V 8 7F 6B 6A 5 4 3 1 VAX-31 HIGH DOSE PHASE 2 NI STUDY VS PCV20: 20 Common STs (OPA GMRs) PCV21 PHASE 3 PIVOTAL NI STUDY VS PCV20: 10 Common STs (OPA GMRs)2 ST = serotypes. NI = noninferiority. * * * * * * * The PCV21 Phase 3 study shows tighter error bars given larger study size and powering Graph Key: GMR at 0.667 * 7 serotypes that reached statistical significance for superiority February 24, 2026 VAX-31 GMRs Higher on 18 of 20 Common STs and 7 STs Achieved Statistically Higher Immune Responses¹
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Descriptive Study Evaluating Safety, Tolerability and Immunogenicity of VAX-31¹ when Administered Either Concomitantly with or One Month Following Administration of a Licensed Seasonal Influenza Vaccine in Healthy Pneumococcal-Naïve² Adults Aged ≥50 Years 28 OPA = opsonophagocytic activity, IgG = immunoglobulin G, HAI = hemagglutination inhibition, SIV = seasonal influenza vaccine. (1) VAX-31 High Dose (all serotypes dosed at 3.3mcg, except serotypes 1, 5, and 22F which are dosed at 4.4mcg) selected to advance to Phase 3. (2) No known prior IPD, pneumococcal pneumonia, or receipt of any licensed or investigational pneumococcal vaccine. February 24, 2026 Randomize (1:1) Screen VAX-31 & SIV: n~650 Placebo VAX-31 OPA & IgG VAX-31, HAI SIV Placebo & SIV: n~650 Day 1 Month 1 Month 6 Month 7Month 2 OPA & IgG VAX-31 Blood Sample Dose Dose Blood Sample Standard Safety Follow-Up: 7 Months After Day 1 Blood Sample OPUS-2 Phase 3 Clinical Trial Evaluating VAX-31 Concomitantly Administered with Seasonal Influenza Vaccine (n~1,300) 28
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PRIOR PPSV23 RECIPIENTS PRIOR PCV20 RECIPIENTS ANY OTHER PNEUMOCOCCAL VACCINE RECIPIENTS, INCLUDING PRIOR PCV21 February 24, 2026 29 Screen Standard 6 Month Safety Follow-Up Blood Sample OPA & IgG VAX-31 Randomize (3:1) Month 1 Month 6Day 1 Blood Sample Dose Descriptive Study Evaluating Safety, Tolerability and Immunogenicity of a Single Dose Of VAX-31¹ in Healthy U.S. Adults Aged 50 Years and Older with a History of Prior Pneumococcal Vaccination² OPA = opsonophagocytic activity, IgG = immunoglobulin G, PPSV23 = Pneumovax 23. (1) VAX-31 High Dose (all serotypes dosed at 3.3mcg, except serotypes 1, 5, and 22F which are dosed at 4.4mcg) selected to advance to Phase 3. (2) Prior pneumococcal vaccination defined as previously receiving PPSV23, PCV20 or any other licensed pneumococcal vaccine ≥6 months prior to administration of the first OPUS-3 dose. OPUS-3 Phase 3 Clinical Trial Evaluating VAX-31 in Healthy Adults Who Have Previously Received a Pneumococcal Vaccine (n~720) VAX-31: n~180 Control Group PCV20: n~60 VAX-31: n~180 Control Group PCV20: n~60 VAX-31: n~180 Control Group PCV20: n~60
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OPUS-2: PHASE 3 TRIAL EVALUATING VAX-31 CONCOMITANTLY ADMINISTERED WITH SEASONAL INFLUENZA VACCINE February 24, 2026 30 Descriptive Phase 3 Studies Designed to Demonstrate VAX-31’s Performance in Real-World Adult Use OPUS-2 and OPUS-3 Phase 3 Clinical Trial Key Objectives OPA = opsonophagocytic activity, HAI = hemagglutination inhibition, GMTs = geometric mean titers, IgG = immunoglobulin G, GMCs = geometric mean concentrations, GMFRs = geometric mean fold rises, SAE = serious adverse events, NOCI = new onset of chronic illnesses, MAAE = medically attended adverse events, AE = adverse events, SIV = seasonal influenza vaccine. • Primary Objective: Assessing serotype-specific immune responses (OPA GMTs and GMFRs) elicited by VAX-31 across all 31 serotypes and serotype 20B in adults who have previously received PPSV23, PCV20 or other prior licensed pneumococcal vaccines or combinations thereof • Secondary Objective: Describing serotype-specific IgG antibody responses (IgG GMCs and GMFRs) elicited by VAX-31 across all 31 serotypes and serotype 20B • Participants will be followed for safety through Month 6 after Dose 1, including SAE, NOCI, and MAAE; Day 1 to Day 7, solicited adverse events will be evaluated; Day 1 to Month 1, all unsolicited AEs will be evaluated OPUS-3: PHASE 3 TRIAL EVALUATING VAX-31 IN HEALTHY ADULTS WHO HAVE PREVIOUSLY RECEIVED A PNEUMOCOCCAL VACCINE KEY IMMUNOGENECITY OBJECTIVES KEY SAFETY & TOLERABILITY OBJECTIVES KEY IMMUNOGENECITY OBJECTIVES KEY SAFETY & TOLERABILITY OBJECTIVES • Primary Objective: Assessing serotype-specific immune responses (OPA GMTs and GMFRs) elicited by VAX-31 across all 31 serotypes and serotype 20B in healthy pneumococcal-naïve adults aged 50 years and older • Primary Objective: Comparing strain-specific immune responses (HAI GMTs) elicited by a SIV when co-administered with VAX-31 to those elicited by a SIV alone • Secondary Objective: Comparing IgG antibody responses (IgG GMCs) elicited by VAX-31 across all 31 serotypes and serotype 20B when VAX-31 is co-administered with a SIV to those elicited by VAX-31 alone • Participants will be followed for safety through Month 7 after Dose 1, including SAE, NOCI, and MAAE; Day 1 to Day 7, solicited adverse events will be evaluated; Day 1 to Month 1, all unsolicited AEs will be evaluated
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Overview: VAX-31 Adult Phase 1/2 Study Results 31February 24, 2026
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Summary of VAX-31 Adult 50+ Phase 1/2 Study Topline Data Findings 32February 24, 2026 Overall study results positive and met objectives Well tolerated, demonstrating a safety profile similar to PCV20 At all doses studied, VAX-31 demonstrated robust OPA immune responses for all 31 STs, all three doses advanceable to Phase 3 VAX-31 High Dose selected to advance to Phase 3 VAX-31 data further validate the potential of Vaxcyte’s carrier-sparing platform to deliver best-in-class PCVs Unprecedented Results Support Potential Best-in-Class PCV With Broadest Serotype and Disease Coverage OPA = opsonophagocytic activity; ST = serotypes.
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0.0 0.5 1.0 1.5 2.0 2.5 33F 23F 22F 19F 19A 18C 15B 14 12F 11A 10A 9V 8 7F 6B 6A 5 4 3 1 VAX-31 Low Dose 0.0 0.5 1.0 1.5 2.0 2.5 33F 23F 22F 19F 19A 18C 15B 14 12F 11A 10A 9V 8 7F 6B 6A 5 4 3 1 VAX-31 High Dose 0.0 0.5 1.0 1.5 2.0 2.5 33F 23F 22F 19F 19A 18C 15B 14 12F 11A 10A 9V 8 7F 6B 6A 5 4 3 1 VAX-31 Middle Dose 33February 24, 2026 Middle and High Doses Met OPA Response Noninferiority Criteria for All 20 Common STs Compared to PCV20 VAX-31 Induced Robust Immune Responses for All 20 Common STs GMR: * * * * * * * * * * * * * Reached statistical significance for superiority. Low Dose: 8 of 20 STs had a GMR greater than 1.0 and 3 STs achieved statistically higher immune responses Middle Dose: 13 of 20 STs had a GMR greater than 1.0 and 5 STs achieved statistically higher immune responses High Dose: 18 of 20 STs had a GMR greater than 1.0 and 7 STs achieved statistically higher immune responses * * * ¹ (1) VAX-31 High Dose (all serotypes dosed at 3.3mcg, except serotypes 1, 5, and 22F which are dosed at 4.4mcg) selected to advance to Phase 3.
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1 10 100 35B 31 23B 23A 20B 17F 16F 15A 9N 7C 2 VAX-31 Induced Robust Immune Responses for All 11 Incremental STs All Three Doses Met Superiority Criteria for All Incremental STs Compared to PCV20 34February 24, 2026 2 7C 9N 15A 16F 17F 20B 23A 23B 31 35B 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% VAX-31 Middle Dose % difference with a > 4-fold OPA titer increase (95% CI) 2 7C 9N 15A 16F 17F 20B 23A 23B 31 35B 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% VAX-31 High Dose 2 7C 9N 15A 16F 17F 20B 23A 23B 31 35B 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% VAX-31 Low Dose 1 10 100 35B 31 23B 23A 20B 17F 16F 15A 9N 7C 2 GMR: 1 10 100 35B 31 23B 23A 20B 17F 16F 15A 9N 7C 2 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 2 on slide 15. (1) VAX-31 High Dose (all serotypes dosed at 3.3mcg, except serotypes 1, 5, and 22F which are dosed at 4.4mcg) selected to advance to Phase 3. ¹
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35 VAX-31 Full Six-Month Safety Data Similar to PCV20 and Across Cohorts February 24, 2026 VAX-31 Low Dose VAX-31 Middle Dose VAX-31 High Dose¹ PCV20 NUMBER OF SUBJECTS WITH: 255 254 253 253 Unsolicited TEAE, n (%) 42 (16.5) 43 (16.9) 47 (18.6) 42 (16.6) Related Unsolicited TEAE, n (%) 7 (2.7) 11 (4.3) 17 (6.7) 12 (4.7) MAAE, n (%) 45 (17.6) 42 (16.5) 35 (13.8) 31 (12.3) Related MAAE, n (%) 1 (0.4) 4 (1.6) 0 0 NOCI, n (%) 2 (0.8) 6 (2.4) 5 (2.0) 5 (2.0) Related NOCI, n (%) 1 (0.4) 0 0 0 SAE, n (%) 2 (0.8) 3 (1.2) 5 (2.0) 3 (1.2) Related SAE, n (%) 0 0 0 0 Death, n (%) 0 0 0 0 Related Death, n (%) 0 0 0 0 TEAE = treatment emergent adverse events, MAAE = medically attended adverse events, NOCI = new onset of chronic illnesses, SAE = serious adverse events. Excludes Solicited AEs. (1) VAX-31 High Dose (all serotypes dosed at 3.3mcg, except serotypes 1, 5, and 22F which are dosed at 4.4mcg) selected to advance to Phase 3.
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PCV Infant Clinical Program
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37February 24, 2026 Percentage of IPD and Pneumococcal Acute Otitis Media Covered by PCVs in U.S. Children IPD1 <5 years All estimates assume cross-protection between serotypes 6A and 6C and between 15B and 15C. (1) CDC 2023 Active Bacterial Core (ABC) Surveillance data; IPD cases with missing serotype data were excluded, non-typeable cases were included in the denominator. (2) In U.S. children five years of age or under, VAX-31 is estimated to address ~96% of AOM: Grant LR et al., FrontPediatr.2024;12:1383748. Serotype percentages reflect 2017–2021 data (Supplemental Table 1). (3) VAX-31 includes all serotypes covered by VAX-24, plus an additional 7 serotypes; VAX-24 coverage is depicted in light green and covers 72% of IPD cases in U.S. children <5 years and 62% of AOM cases in U.S. children <5 years. 48% 69% 92% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% VAX-31PCV20PCV15 VAX-24³ 34% 61% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 96% Pneumococcal Acute Otitis Media2 <5 years VAX-31PCV20PCV15 VAX-24³ VAX-31 Designed to Expand Protection with Broadest Disease Coverage in Children
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4 6B 9V 14 18C 19F 23F 1 5 7F 3 6A/C² 19A 22F 33F 8 10A 11A 12F 15B/C² 9N 17F 20³ 2 15A 16F 23A 23B 31 35B 7C Total Coverage¹ 92% 72% 69% 48% February 24, 2026 38 VAX-31 Designed to Deliver Broadest Disease and Serotype Coverage in Infants, Including ~92% of Invasive Pneumococcal Disease (IPD) in U.S. Children¹ (1) % of IPD caused in individuals <5 yrs of age in the U.S. in 2023 based on ABC surveillance data: https://data.cdc.gov/Public -Health-Surveillance/1998-2023-Serotype-Data-for-Invasive-Pneumococcal-/qvzb-qs6p/about_data. (2) Serotypes 6A/6C and 15B/15C are closely related subtypes for which cross -protection is assumed. PCV20 and VAX -31 include 15B, and all three—PCV15, PCV20, and VAX-31— include 6A. (3) Serotype 20 comprises closely related subtypes for which cross -protection is assumed. Within the serotype 20 group, strain 2 0B is the predominant circulating strain and shows greater genetic similarity to 20C compared to 20A. PCV21 includes 20A, VAX-31 includes 20C, with 20B planned to be evaluated in clinical studies to demonstrate cross protection. T he 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 2 on slide 15. % of IPD in U.S. children <5 yrs of age¹ VAX-31 0.7% 0.0% 0.0% 0.0% 0.7% 13.8% 0.0% 0.0% 0.0% 0.7% 14.5% 0.0% 1.4% 9.7% 6.2% 0.0% 3.4% 4.8% 0.0% 13.1% 1.4% 0.0% 1.4% 0.0% 6.2% 0.7% 3.4% 4.8% 0.7% 4.1% 0.0% PCV20 PCV15 VAX-31’s UNIQUE 11 STs: Across multiple adult and infant studies, Vaxcyte’s PCVs have shown strong immune responses across all incremental STs relative to PCV20. VAX-31, in particular, could significantly increase coverage versus today’s standard-of-care. VAX-31’S UNIQUE STs HAVE POTENTIAL TO PROVIDE 23-44% MORE IPD COVERAGE COMPARED TO CURRENT STANDARD-OF-CARE INFANT PCVs LEGACY SHARED 20 STs: In the infant study, VAX-24 had higher responses on the highest circulating STs (3 & 19F) and while there were some lower relative responses compared to PCV20, they were restricted to a small subset of shared STs with limited residual disease. Legacy Shared STs Unique STs VAX-24
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Total Coverage¹ 96% 62% 61% 34% February 24, 2026 39 VAX-31 Designed to Deliver Broadest Disease and Serotype Coverage in Infants, Including ~96% of Pneumococcal Acute Otitis Media (AOM) in U.S. Children¹ (1) In children five years of age or under, VAX -31 is estimated to address ~96% of AOM: Grant LR et al., FrontPediatr.2024;12:1383748. Serotype percentages reflect 2017 –2021 data (Supplemental Table 1) . (2) Serotypes 6A/6C and 15B/15C are closely related subtypes for which cross -protection is assumed. PCV20 and VAX -31 include 15B, and PCV15 and VAX-31 include 6A. (3) Serotype 20 comprises closely related subtypes for which cross -protection is assumed. Within the serotype 20 group, strain 2 0B is the predominant circulating strain and shows greater genetic similarity to 20C compared to 20A. PCV21 includes 20A, VAX-31 includes 20C, with 20B planned to be evaluated in clinical studies to demonstrate cross protection. T he 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 2 on slide 15. % of AOM in U.S. children <5 yrs of age¹ 0.0% 0.0% 0.0% 0.0% 1.0% 11.3% 0.0% 0.0% 0.0% 0.0% 6.2% 1.0% 4.1% 4.1% 6.2% 0.0% 2.1% 5.2% 2.1% 17.5% 0.0% 1.0% 0.0% 0.0% 8.2% 3.1% 4.1% 8.2% 1.0% 9.3% 0.0% VAX-31’s UNIQUE STs VS STANDARD-OF-CARE INFANT PCVs: Potential to Provide 35-62% Increase in AOM Coverage Compared to Current Standards-of-Care Infant PCVs Legacy Shared STs Unique STs VAX-31’S UNIQUE STs COMPARED TO CURRENT INFANT STANDARD-OF-CARE PCVs 4 6B 9V 14 18C 19F 23F 1 5 7F 3 6A/C² 19A 22F 33F 8 10A 11A 12F 15B/C² 9N 17F 20³ 2 15A 16F 23A 23B 31 35B 7C VAX-31 VAX-24 PCV20 PCV15
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40February 24, 2026 Healthcare Providers Confirm: Broader Coverage Wins in PCV Selection More than three- quarters of HCPs (76%) would transition mid- series to a higher-valent PCV optionof HCPs prefer higher coverage PCVs, and 80% agree higher coverage will reduce IPD U.S. pediatric and family medicine providers overwhelmingly favor broader-coverage PCVs and would take action to expand protection for infants.¹ say protection against acute otitis media is an important vaccine feature 93% 76% BROAD PROTECTION DRIVES HCP ADOPTION would switch infants to broader-coverage PCV even mid-series to maximize protection would prescribe another dose of broader-coverage PCV for already-vaccinated children under 5 PROVIDERS WOULD SWITCH MID-SERIES WILLINGNESS TO PRESCRIBE “CATCH UP” OTITIS MEDIA PREVENTION MATTERS 76% 60% 84% HCP = healthcare provider. (1) Cross-sectional web survey conducted by Pfizer in October-November 2022; sponsor-affiliated and conducted prior to policy finalization, reflects stated intentions rather than observed behavior and does not represent real-world uptake https://www.tandfonline.com/doi/full/10.1080/14760584.2025.2585808#abstract.
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VAX-24 Infant Phase 2 Dose-Finding Study Final Results 41February 24, 2026
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Final VAX-24 Phase 2 Infant Study Results and Platform Demonstrate Potential to Achieve Broadest Coverage of Any Infant PCV On-Market 42February 24, 2026 Overall study results positive and met objectives Well tolerated, demonstrating a safety profile similar to PCV20 VAX-24 elicited substantial IgG, OPA and memory responses and performed particularly well against currently circulating serotypes contained in the vaccine Results consistent with previously reported positive interim results; provide additional evidence validating rationale for exploring higher doses in ongoing VAX-31 infant Phase 2 dose-finding study Substantial, dose-dependent immune responses and little to no evidence of carrier suppression observed
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Stage 1: Dose Escalation (n=48*) Stage 2: Main Study (n=789*) 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 February 24, 2026 Randomized, Observer-Blind, Active-Controlled, Dose-Finding, Clinical Study to Evaluate Safety, Tolerability and Immunogenicity of VAX-24 vs. Standard-of-Care (PCV20) in 803 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 in Stage 2 and followed separately; they are not included in the safety or immunogenicity evaluable populations. Two (2) subjects withdrew after being randomized in Stage 2. All 36 VAX-24 subjects from Stage 1 proceeded to Stage 2 43 VAX-24 Infant Phase 2 Dose-Finding Clinical Study (N=803)
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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 February 24, 2026 3 19F 15B2 22F 33F 11A 10A 19A 18C 7F 4 8 6B 12F 9V 14 23F 5 6A 1 9N 20C3 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 included 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. 44 % of IPD in U.S. 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. (2) 15C coverage due to cross protection against 15B. 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 2 on slide 15.
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Final 6-Month Safety Data from VAX-24 Phase 2 Study Safety Results Similar to PCV20 and Across Cohorts February 24, 2026 VAX-24 Low Dose VAX-24 Mid Dose VAX-24 Mixed Dose PCV20 NUMBER OF SUBJECTS 195 186 191 185 Unsolicited TEAE, n (%) 167 (85.6) 161 (86.6) 163 (85.3) 169 (91.4) Related Unsolicited TEAE, n (%) 6 (3.1) 13 (7.0) 13 (6.8) 6 (3.2) MAAE, n (%) 172 (88.2) 155 (83.3) 167 (87.4) 161 (87.0) Related MAAE, n (%) 3 (1.5) 3 (1.6) 3 (1.6) 1 (0.5) NOCI, n (%) 12 (6.2) 12 (6.5) 15 (7.9) 10 (5.4) Related NOCI, n (%) 0 1 (0.5)1 0 0 SAE, n (%) 10 (5.1) 7 (3.8) 11 (5.8) 11 (5.9) Related SAE, n (%) 0 0 0 0 Death, n (%) 0 0 0 1 (0.5)2 Related Death, n (%) 0 0 0 0 TEAE = treatment emergent adverse events, NOCI = new onset of chronic illnesses, MAAE = medically attended adverse events, SAE = serious adverse events. (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. 45
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Final Post-Dose 3 (PD3) IgG and OPA Immunogenicity Data Results 46February 24, 2026
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February 24, 2026 47 Met Precedent Phase 2 Noninferiority Criteria for 20 of 24 STs at Low and Mid Doses and 19 of 24 STs at Mixed Dose 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 -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 60 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 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 U.S. children <5 yrs of age1 Difference in % of Subjects Meeting Predefined IgG Levels Difference in % of Subjects Meeting Predefined IgG Levels NI = noninferiority; 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). 15C coverage due to cross protection against 15B. 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 2 on slide 15. X = STs dosed at 4.4mcg. POST-DOSE 3 RESULTS = Point Estimate. -30 -15 0 15 30 45 2 17F 20C 9N -30 -15 0 15 30 45 2 17F 20C 9N -30 -15 0 15 30 45 60 2 17F 20C 9N
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February 24, 2026 48 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 15C coverage due to cross protection against 15B. 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 2 on slide 15. Serotype 20B was studied in this OPA analysis. POST-DOSE 3 RESULTS Demonstrated Robust OPA Titers, Generally Consistent with IgG Responses
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Final Post-Dose 4 (PD4) IgG and OPA Immunogenicity Data Results 49February 24, 2026
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VAX-24 Demonstrated High Overall Seroconversion Rates Across All Doses PD4 February 24, 2026 50 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 15C coverage due to cross protection against 15B. 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 2 on slide 15. IgG = immunoglobulin G. POST-DOSE 4 RESULTS
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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 February 24, 2026 51 Met Target Ph2 Noninferiority Criteria for Point Estimate of >0.6 on 19 of 24 STs at Mixed Dose and 18 of 24 STs at Mid Dose VAX-24 PD4 IgG GMRs Compared to PCV20 IgG Geometric Mean Ratios for VAX-24 vs. PCV202 0 2 4 6 8 10 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 3.0 1 6A 5 23F 14 9V 12F 6B 8 4 7F 18C 19A 10A 11A 33F 22F 15B 19F 3 0 2 4 6 8 10 2 17F 20C 9N 0 2 4 6 8 10 2 17F 20C 9N % of IPD in U.S. 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 0.7% 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) GMRs 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). 15C coverage due to cross protection against 15B. 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 2 on slide 15. X = STs dosed at 4.4mcg. POST-DOSE 4 RESULTS
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February 24, 2026 52 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 PD4 OPA GMT Immune Responses 15C coverage due to cross protection against 15B. 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 2 on slide 15. Serotype 20B was studied in this OPA analysis. POST-DOSE 4 RESULTS Demonstrated Robust OPA Titers, Generally Consistent with IgG Responses
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February 24, 2026 53 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 Pre-Dose 4 VAX-24 Mid Dose Post-Dose 4 VAX-24 Demonstrated Robust Memory Responses Pre- vs Post-Dose 4 IgG GMCs Non-PCV20 SerotypesSerotypes Contained in PCV20 15C coverage due to cross protection against 15B. 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 2 on slide 15. IgG = immunoglobulin G.
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Expanded Analysis of Concomitant Flu Vaccination & Dose-Dependent Immune Responses 54February 24, 2026
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0.0 0.5 1.0 1.5 2.0 10A - IEP4 + Flu 10A - IEP4 9V - IEP4 + Flu 9V - IEP4 8 - IEP4 + Flu 8 - IEP4 7F - IEP4 + Flu 7F - IEP4 6B - IEP4 + Flu 6B - IEP4 6A - IEP4 + Flu 6A - IEP4 5 - IEP4 + Flu 5 - IEP4 4 - IEP4 + Flu 4 - IEP4 3 - IEP4 + Flu 3 - IEP4 1 - IEP4 + Flu 1 - IEP4 0.0 0.5 1.0 1.5 2.0 33F - IEP4 + Flu 33F - IEP4 23F - IEP4 + Flu 23F - IEP4 22F - IEP4 + Flu 22F - IEP4 19F - IEP4 + Flu 19F - IEP4 19A - IEP4 + Flu 19A - IEP4 18C - IEP4 + Flu 18C - IEP4 15B - IEP4 + Flu 15B - IEP4 14 - IEP4 + Flu 14 - IEP4 12F - IEP4 + Flu 12F - IEP4 11A - IEP4 + Flu 11A - IEP4 February 24, 2026 GMR 55 Consistently Improved Immunogenicity Responses Evidenced in Mid Dose VAX-24 PD4 IgG GMRs Compared to PCV20 Including Subjects Who Received Flu Vaccination IgG Geometric Mean Ratios for VAX-24 vs. PCV20 POST-DOSE 4 RESULTS The IEP4 includes eligible subjects who received the same vaccine across all 4 doses, with valid PD4 IgG or OPA assay results based on blood sample collected within protocol-defined window, and without protocol deviations that may interfere with PD4 immune response. The IEP4 + Flu population includes all eligible subjects from the IEP4 population and an additional 12 participants who followed protocol and received a flu vaccine. This is not a complete study evaluating the concomitant administration of VAX-24 with other vaccines. The findings presented are limited in scope and are not necessarily indicative of how VAX-24 would perform in studies designed to assess concomitant administration. Population: Immunogenicity Evaluable Population (IEP): 119 IEP + Concomitant Flu Vaccine: 130
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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 0.0 0.5 1.0 1.5 2.0 2.5 19F 19A 18C 9V 7F 6B 3 IgG GMR Supports Dosing Strategy for Ongoing VAX-31 Infant Phase 2 Study Dose Response Evidenced PD4 Across Most Serotypes 56February 24, 2026 DOSE-DEPENDENT IMMUNOGENICITY OBSERVED ACROSS DOSE RANGE1 LITTLE TO NO CARRIER SUPPRESSION EVIDENCED BY SIMILAR PERFORMANCE ACROSS DIFFERENT LEVELS OF PROTEIN CARRIER CONTENT PD4 IgG GMR GMR Dose- Dependent Responses Demonstrate Potential for Optimization PD4 IgG GMC 17 STs dosed at 2.2 mcg at both Mid and Mixed Doses2 POST-DOSE 4 RESULTS (1) Data represent 7 STs dosed at 1.1, 2.2 and 4.4 mcg. (2) 15C coverage due to cross protection against 15B.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 2 on slide 15.
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VAX-31 Infant Clinical Program
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End Stage 1 - Proceed Dose 2 3-Stage, Dose-Finding Study Evaluating Safety, Tolerability and Immunogenicity vs PCV20 in 900 Participants Enrollment Completed in VAX-31 Infant Phase 2 Study Stage 1: Dose Escalation (n=48)Randomized Screen VAX-31 Low Dose PCV20 Dose 1 VAX-31 Middle Dose PCV20 VAX-31 High Dose PCV20 Dose 1 Dose 1 Stages 2 & 3: Main Study (n=900*) Randomized Screen All Stages: PCV20 All Stages: VAX-31 Middle Dose (2.2mcg¹) All Stages: VAX-31 High Dose (3.3mcg¹) Stage 3: VAX-31 Optimized Dose (4.4mcg/3.3mcg) Stages 1-2: VAX-31 Low Dose (1.1mcg¹) Age 2 months Dose 1 4 months 6 months 7 months 12-15 months Dose 2 Dose 3 Primary Series Immunogenicity Endpoint Dose 4 Long-Term Safety 13-16 months Booster Immunogenicity Endpoint Stage 1 (safety review; completed): The safety and tolerability of VAX-31 was evaluated at three dose levels (Low, Middle and High) and compared to PCV20 in 48 infants in a dose-escalation approach. Stage 2 (modified and incorporated into Stage 3): Evaluating the safety, tolerability and immunogenicity of VAX-31 at the same three dose levels and compared to PCV20. The study includes a primary immunization series with doses given at two, four and six months of age, followed by a booster dose at 12-15 months of age. Stage 3 (enrollment completed): The modified study, including the VAX-31 Optimized Dose arm, has completed enrollment in the third and final stage of the study. The Middle and High Dose arms are continuing in Stage 3 as planned. All participants will be evaluated for safety through six months after the booster dose. Age 2 months Age 2 months Age 2 months (*) n=900, inclusive of the 48 subjects from Stage 1. (1) Except serotypes 1, 5 and 22F, which were dosed at 1.65mcg, 3.3mcg, and 4.4mcg, respectively. 6 months February 24, 2026 58
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Study Safety, Tolerability and Immunogenicity Key Outcome Measures SAFETY AND TOLERABILITY OUTCOME MEASURES IMMUNOGENICITY OUTCOME MEASURES February 24, 2026 59 DAY 7 AFTER EACH DOSE 1 MONTH POST-DOSE 3 1 MONTH POST-DOSE 4 6 MONTHS POST-DOSE 4 • Solicited local reactions • Solicited systemic events • Unsolicited adverse events (AE) • Serious adverse events (SAE), new onset of chronic illnesses (NOCI) and medically attended adverse events (MAAE) • SAE, NOCI and MAAE • SAE, NOCI and MAAE • % of subjects achieving Immunoglobulin G (IgG) antibody concentration ≥0.35 mcg/mL • IgG Geometric Mean Concentration (GMC) • Opsonophagocytic activity (OPA) Geometric Mean Titer (GMT) • IgG GMC • % of subjects achieving IgG antibody concentration ≥.35 mcg/mL • % of subjects achieving IgG concentration ≥1.0 mcg/mL • OPA GMT • IgG and OPA Geometric Mean Fold Rise (GMFR) from pre-dose 4 to 1-month post-dose 4 • % of subjects achieving a 4-fold rise in IgG and OPA from pre- dose 4 to 1-month post-dose 4
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New slide/format Non-PCV Pipeline
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VAX-A1: BROAD-SPECTRUM, MONOVALENT CONJUGATE VX February 24, 2026 61 Phase 1 Adult Study Includes Primary Objective of Assessing Safety and Tolerability of VAX-A1, a Novel Conjugate Vaccine Designed to Deliver Universal Protection Against a High-Priority Pathogen Initiation of Phase 1 Adult Clinical Study for VAX-A1, a Vaccine Candidate to Prevent Group A Strep, Expected in 2026¹ (1) Guidance as of February 24, 2026. (2) https://www.nature.com/articles/s41541-023-00690-2.pdf. (3) https://academic.oup.com/cid/article/77/6/917/7180116. (4) https://pubmed.ncbi.nlm.nih.gov/34192307/#:~:text=Results:%20Costs%20of%20invasive%20GAS,associated%20with%20invasive%20GAS%20disease. (5) https://jamanetwork.com/journals/jama/fullarticle/2832277. Group A Strep remains a global cause of morbidity and mortality in adults and children: • Group A Strep results in an estimated 800M cases of illness annually worldwide, including pharyngitis, or strep throat, and an array of severe invasive infections and sequelae³ • Annual economic burden of Group A Strep disease in the U.S. population is estimated to exceed $6 billion⁴ • Studies have indicated that antibiotic resistance to Group A Strep has been increasing over the past decade, leading the CDC to categorize Group A Strep as a concerning threat⁵ Conjugate vaccine combining a disease-specific protein carrier and a universal species-defining PS designed to confer robust, boostable and durable protection against a broad-spectrum of subtypes of Group A Strep Leverages site-specific conjugation to disease-specific carrier to expose mapped T- and B-cell epitopes Proprietary conserved antigen – Polyrhamnose – conjugated to an immunogenic disease-specific carrier along with two conserved virulence factors KEY DATA: Mock SLO + C5a pep SpyAD-GACPR VAX-A1 (SLO + C5a pep + SpyAD-GACPR) TOTAL ANNUAL MARKET FOR GROUP A STREP VACCINES IS ESTIMATED AT ~$3 BILLION TO $4 BILLION GLOBALLY² 0% 10% 20% 30% 0 10,000 20,000 30,000 2012 2014 2016 2018 Number of Invasive Cases Clindamycin Resistance Erythromycin Resistance Tetracycline Resistance Sharp increase in cases and resistance over a decade:
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VAX-GI: Shigella Vaccine Program (1) Shigellosis: CDC Yellow Book 2024. (2) https://www.who.int/publications/i/item/9789240036741. UNMET NEED • Shigella is a bacterial illness with no available preventative treatment • Estimated to cause 80-165 million cases of disease and 600,000 deaths annually, and most cases and deaths are among children¹ • With the aim of reducing morbidity and mortality due to the disease, the World Health Organization lists Shigella vaccine development as a priority goal² VAX-GI: NOVEL SHIGELLA VACCINE • Development collaboration with the University of Maryland, Baltimore; supported with funding by two National Institutes of Health grants with total potential funding of up to $5.1M • Plan to pursue conjugate and protein-only approaches simultaneously • Conjugate approach: IpaB-LPS/IpaH/VirG; Protein-only approach: IpaB/IpaH/VirG PROGRAM STATUS • Decision on final candidate to be determined by a human challenge study conducted at the University of Maryland, Baltimore MOA & KEY DATA • Targeting IpaB inhibits assembly of T3SS and toxin delivery to immune cells • Opsonophagocytosis and killing of bacteria February 24, 2026 62 Novel Shigella Vaccine to Prevent Widespread Global Morbidity & Mortality, Particularly in Children 0 2 4 6 8 10 12 14 0 20 40 60 80 100 Days after challenge % Survival * * * * VAX-GI: Conjugate Approach VAX-GI: Protein Only Approach Candidate Vaccine Antigen T3SS 0 2 4 6 8 10 12 14 0 20 40 60 80 100 Days after challenge % Survival IpaB 5µg IpaB-10µg IpaB-20µg sl Sf2a-IN * * AdjuPhos PBS * *
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63February 24, 2026 Key Corporate Highlights Cell-Free Protein Synthesis Enabled Pipeline Robust Pipeline with Multiple Novel Vaccines Aligned Critical Commercial Manufacturing and Supply Chain Resources Large Market Opportunity for Broadest-Spectrum PCV
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Appendix 64February 24, 2026
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65February 24, 2026 PPSV23 PCV13 PCV15 PCV20 PCV21 VAX-31 Total IPD Coverage (U.S. %)3 70.6% 34.4% 47.3% 61.1% 81.2% 94.8% (1) 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 2 on slide 15. (2) 15C coverage due to cross-reaction against 15B. 6C coverage due to cross-protection by 6A. (3) % of IPD caused in individuals ≥50 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. VAX-31: • Positioned to provide unrivaled IPD coverage as the broadest-spectrum PCV to enter U.S. clinics; designed to increase coverage to approximately 95% of IPD circulating in U.S. adults • Includes serotypes to provide protection against both currently circulating and historically prevalent serotypes, with potential to surpass standard-of-care adult PCVs with 14-34% incremental coverage Spectrum of Coverage Drives Adoption in PCV Segment VAX-31 Designed to Increase Coverage to ~95% of IPD Circulating in U.S. Adults 18.75% 10.62% 6.35% 5.64% 5.39% 4.88% 4.78% 3.96% 3.86% 3.71% 3.35% 3.00% 2.90% 2.49% 2.34% 2.29% 1.98% 1.88% 1.83% 1.63% 1.58% 1.47% 1.37% 1.27% 0.97% 0.46% 0.25% 0.20% 0.20% 0.10% 0.10% 0.05% 0.05% 0.05% 0.05% 0.05% 0.00% 0.00% 0.00% 0.00% 0.00% 0.00% 2.00% 4.00% 6.00% 8.00% 10.00% 12.00% 14.00% 16.00% 18.00% 20.00% 3 22F 4 9N 23A 19F 20 15A 11A 35B 12F 16F 15B/C 23B 33F 8 7C 6A/C 31 19A 34 35F 10A 38 17F 7F 28A 9V 13 21 23F 10F 14 18A 18C 33A 1 2 5 6B 24F 21 2
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66February 24, 2026 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 IPD Coverage (U.S. %)4 47.6% 69.0% 71.7% 91.7% PCV15 PCV20 VAX-24 VAX-31 (1) 15C coverage due to cross-reaction against 15B. 6C coverage due to cross-protection by 6A. (2) 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 2 on slide 15. (3) In U.S. children five years of age or under, VAX-31 is estimated to address ~96% of AOM: Grant LR et al., FrontPediatr.2024;12:1383748. Serotype percentages reflect 2017–2021 data (Supplemental Table 1). (4) % of IPD caused in individuals <5 yrs of age in the U.S. in 2023 based on ABC surveillance data: https://data.cdc.gov/Public-Health-Surveillance/1998-2023-Serotype-Data-for-Invasive-Pneumococcal-/qvzb-qs6p/about_data. 1 2 Pediatric Segment Represents Majority of ~$8B Pneumococcal Vaccine Market Spectrum of Coverage Drives Adoption in Vital Pediatric Population VAX-24: Broadest-spectrum profile designed to cover more serotypes than any pediatric pneumococcal vaccine on- market today. VAX-31: 31-valent PCV with potential to increase serotype coverage and address ~96% of acute otitis media.3 1
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6A Others* 3 1 10 100 1000 10000 % Protective Threshold PCV20 PCV15 67 (1) Lancet Infect Dis. 2014 Sep;14(9): 839-846. (2) PCV20 product insert – Table 11. (3) PCV15 product insert – Table 11. Protective threshold Serotype * = 1, 4, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F. Serotype 3 (ST3) Conjugate Elicits Weakest Antibody Response Among All Conjugates On-Market PCVs Elicit Antibodies for Disease Protection With Range of Results KEY FACTORS DETERMINE WHY ST3 REQUIRES HIGHER LEVEL OF PROTECTIVE ANTIBODY ST3 REMAINS AN OUTLIER AS CIRCULATION HAS NOT BEEN EFFECTIVELY CONTROLLED BY VACCINATION Thick Polysaccharide Capsule: forms a robust physical barrier that impairs opsonization and phagocytosis, requiring higher antibody levels for effective coating Capsule Shedding and Antibody Neutralization: releases free polysaccharides that bind and neutralize antibodies before they reach the bacterial surface Reduced Opsonophagocytic Efficiency: mucoid capsule limits complement (C3b) deposition and phagocyte recognition, making ST3 less susceptible to immune clearance February 24, 2026 ¹ ² ³ ¹
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Contact: Jeff Macdonald, Executive Director, Investor Relations investors@vaxcyte.com