Vaxcyte : May Investor Presentation (8a5ec2)

Corporate Presentation

May 6, 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

Enrollment Completed in VAX-31 OPUS-1 Phase 3, Noninferiority Trial Designed to Establish Fulsome Coverage for Adults

POTENTIAL BEST-IN-CLASS PCV FRANCHISE Carrier-sparing, site-specific conjugation platform enabling broader-spectrum PCVs Adult Indication: VAX-31: Broadest-spectrum PCV in the clinic Enrollment completed in OPUS-1, OPUS-2 and OPUS-3 Phase 3 trials 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

HIGHLY ATTRACTIVE PCV MARKET 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

EXCLUSIVE CELL-FREE PLATFORM 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 mid-2026¹ VAX-GI: Novel Shigella vaccine

ALIGNED CRITICAL RESOURCES 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 ~$2.7 billion in cash, cash equivalents and investments as of 3/31/26

BTD = Breakthrough Therapy designation, IPD = invasive pneumococcal disease, MOA = mechanism of action.

(1) Guidance as of May 6, 2026. The VAX-A1 Phase 1 adult clinical study has the primary objective of assessing safety and tolerability and will be conducted in Australia.

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Cell-Free Protein Synthesis Platform Unlocks Multiple Vaccine Applications

Facilitates Design and Production of Proteins Beyond the Reach of Conventional Methods

VAXCYTE CELL-FREE

PROTEIN SYNTHESIS PLATFORM: XpressCF

• 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

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• Permits protein production in non-physiological conditions

  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

Pipeline of High-Fidelity Vaccines with Multiple Near-Term Milestones

Broad-Spectrum Conjugate and Novel Protein Vaccines to Prevent Bacterial Infectious Diseases

Preclinical Phase 1 Phase 2 Phase 3 Approved Anticipated 2026 and 2027 Key Milestones¹

31-Valent

PCV Candidate

VAX-31

Adults

Infants

Infants

Third-Generation

PCV Candidate

VAX-XL

Adults & Infants

Adults & Infants

Novel Shigella

Vaccine

VAX-GI

Adults & Infants

VAX-A1

Novel Group A

Strep Vaccine

VAX-24

24-Valent

PCV Candidate

VAX-A1

• Initiate Phase 1 adult clinical study in mid-2026, with the

primary objective of assessing safety and tolerability

VAX-31 ADULT INDICATION

• 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-3² trials in the first half of 2027

  VAX-31 INFANT INDICATION

  • 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 the first half of 2027

1. Guidance as of May 6, 2026.

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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.

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Chris Griffith, MS, MBA

Chief Business & Strategy Officer

Grant Pickering, MBA Chief Executive Officer & Co-Founder

Jeff Fairman, PhD

VP Research & Co-Founder

Roger Nosal

Senior VP

& Head of Global Regulatory & Quality

Mike Mullette, MBA

Chief Commercial Officer

Jim Wassil, MS, MBA

Executive VP

& Chief Operating Officer

Harp Dhaliwal, MBA

Chief Technical Operations Officer

Andrew Guggenhime, MBA

President

& Chief Financial Officer

Experienced Management Team with Track Record in Vaccines and Biopharma

PCV

Opportunity

Global Health Impact of Pneumococcal Disease Remains Significant

ABOUT STREPTOCOCCUS PNEUMONIAE 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.		CURRENT ~$8 BILLION GLOBAL VACCINE CATEGORY 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)		GLOBAL INCIDENCE & IMPACT OF PD STILL SUBSTANTIAL 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

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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Serotype Replacement Drives Need for Broader-Spectrum Vaccines

Non-Vaccine Serotypes Increase in Prevalence, as Circulation of Vaccine Serotypes is Eliminated, Resulting in the Need for Broader-Spectrum Vaccines

UK IPD CASES IN ADULTS > 651

30

25

20

Prevnar 13 Types Non-vaccine Types

Residual disease driven by incremental 11 strains over and above PCV13.

Cases

Per 100,000

15

10

5

0

(1) Ladhani et al, Lancet Infect Dis 2018 Apr;18(4):441-45 inclusive of unpublished raw data.

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2000 2005 2010 2015

PCV13 highly effective in prevention of IPD and circulation of included strains.

Limitations of Current PCVs

Coverage Expansion Needed to Address Circulating Disease, but Protein Carrier Backbone Problematic

90

LIMITATIONS OF CONVENTIONAL CHEMISTRY

• Random conjugation masks on-target T-cell 80

  epitopes on the protein carrier

  •

  70

  Conventional reductive amination

  chemistry requires higher amounts of

  60

  protein carrier than polysaccharide to form

  stable conjugates

  50

• Overabundance of protein carrier

  exacerbates carrier suppression, due to 40

  competition for CD4+ help between

  disease-specific polysaccharides and non- 30

  disease specific protein carrier

  20

  PROTEIN CARRIER DIVERTS IMMUNE RESPONSE

  Protein Carrier (mcg)

  Discrete Pneumococcal Polysaccharides (ug)

  65

  51

  46

  34

  31

  20

  16

  84

  10

  0

  Sources: Prevnar 7, Prevnar 13, Prevnar 20, Vaxneuvance and Capvaxive product inserts.

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  Prevnar 7 Prevnar 13 Prevnar 20 Capvaxive

  Limitations of Current PCVs: Adding Conjugates Results in Lower Ab Titers

  Coverage Expansion Using Conventional Chemistry Has Led to Carrier-Induced Immune Suppression

  CARRIER SUPPRESSION

  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

    INFANT IMMUNE RESPONSES (IgG):

    PCV20 VS PCV131

    ADULT IMMUNE RESPONSES (OPA):

    PCV20 VS PCV132

    GMR

    1

    
    
    

    3

    4

    5

    6A

    6B

    7F

    9V

    14

    18C

    19A

    19F

    23F

    0.0 0.5 1.0 1.5

    GMR

    1

    
    
    

    3

    4

    5

    6A

    6B

    7F

    9V

    14

    18C

    19A

    19F

    23F

    0.0 0.5 1.0 1.5

    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.

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    Vaxcyte's PCV Franchise Employs Carrier-Sparing Conjugates

    Cell-Free Platform Enables Precise Conjugation to Enhance Potency of Standard Protein Carrier

    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)

    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

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Vaxcyte PCV Franchise Design Leverages Many Standard PCV Conventions

Utilizes Proven Components, Chemistries and Assays to Reduce Risk and Uncertainty

Polysaccharide Protein Carrier Assays

CDAP / Periodate Activation

Amination for Labeling PS

Incorporation of Non-natural AAs

Random

Lysine Conjugation

Site-Specific

Click Chemistry

Conjugation

CQA

Release Assays

(Mol Wt, Free PS)

Serological

Assays

(IgG & OPA)

Pfizer/Merck Methods

Vaxcyte

incorporation of nnAA conjugation anchors

OPA = opsonophagocytic activity; IgG = immunoglobulin G.

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Novel Enablement: Site-specific conjugation via

Vaxcyte's PCV Franchise Has More Fulsome Coverage Versus On-Market PCVs

Pneumococcal Vaccines Represent One of the Largest Segments of Global Vaccine Market, with Significant Growth Expected¹

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: 24-valent PCV designed to cover more serotypes than any pediatric pneumococcal vaccine on-market today

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

VAX-24

VAX-31

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.

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Pneumococcal Vaccine Market is Highly Attractive

Vaxcyte's PCV Franchise Has the Potential to Be Best-in-Class Due to Broader Coverage and Improved Immunogenicity

PNEUMOCOCCAL VACCINE MARKET DYNAMICS SEROTYPE & DISEASE COVERAGE ADVANTAGE IS PRIMARY DRIVER OF U.S.

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

  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)

  PCV MARKET ADOPTION

  98%

  2%

  PCV15
  
  PCV20
  
  

  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: $299

̶ PCV15: $239 (pediatric)

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

    PCV VACCINATION IN ADULTS AGED ≥ 65

    JULY 2021 - NOVEMBER 20232

    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 (accessed April 2026).

    2. FDA safety assessment of PCV20 data presented at February 2024 ACIP meeting.

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  • Broader-spectrum of serotype and disease coverage drove 98% adoption for PCV20 over PCV15 despite ACIP recommendation of both vaccines

Pneumococcal Vaccine Market Poised for Significant Growth

Combined $8B Market Expected to Grow to ~$12B in 2030¹, Driven Primarily by Adult Market Expansion

Future Market 2030: ~$12B

Pediatric market highly penetrated; significant growth opportunity in adult segment

EXPECTED ADULT SEGMENT GROWTH DRIVERS

"At risk" adults aged 19-49 included in U.S. recommendation

(1)

(2)

(3)

ZS Associates, Vaccine Landscape Report - Pneumococcal infections, April 2026.

https://www.cdc.gov/pneumococcal/hcp/vaccine-recommendations/.

Current revaccination recommendations primarily apply to individuals previously vaccinated with lower-valency pneumococcal regimens (e.g., PCV13 ± PPSV23).

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Revaccination of individuals with history of lower valency pneumococcal vaccination³

Potential shift to adult prime-boost schedule in U.S.

PCV recommendation expanded to U.S. adults 50+ (from 65+)²

Total Market Today: ~$8B

Expanded OUS adult PCV recommendations

Recent Burst of Adult PCV Recommendations Outside the U.S.

Serotype Epidemiology, Broad-Valency PCVs Driving New Recommendations and Shift from PPSV23 to PCVs

Licensure of broader-spectrum PCVs is driving adult universal recommendations internationally

Japan

Switzerland

France Spain (Regional)

International revenues for the Prevnar vaccine family increased ~8% year-over-year²

Germany

Expanded Global Adult PCV

Adoption

PRIOR ADULT

United Kingdom

RECOMMENDATION:

Netherlands

No Prior Universal,

Age-Based PCV Recommendation or PPSV23 Only

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 full-year 2025 earnings reporting, full-year 2024 vs. full-year 2025; Prevnar family includes revenues from Prevnar 20/Prevenar 20 (pediatric and adult) and Prevnar 13/Prevenar 13 (pediatric and adult).

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Establishing Manufacturing Capacity, Robust Supply Chain to Support Expected VAX-31

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Adult U.S. Launch, Followed by U.S. Infant and Global Adult and Infant PCV Launches

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

U.S. Fill-Finish Manufacturing Agreement with Thermo Fisher

• Agreement expands domestic capacity (North Carolina)

• Supports future commercial manufacturing and deepens investment in American innovation and infrastructure

New slide/format

VAX-31

Adult Clinical Program