#1Vaxcyte Corporate Presentation November 10, 2021#22 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 benefits of Vaxcyte's vaccine candidates; the process and timing of anticipated future development of Vaxcyte's vaccine candidates, including the timing and submission of an IND application for VAX-24 and the initiation of the VAX-24 Phase 1/2 clinical proof-of-concept study thereafter; the timing and availability of topline data for VAX-24; the ability to complete the manufacturing of the GMP drug product; the successful testing and release of the final drug product for VAX-24 and documentation of stability; the achievement of future funding milestones; the use and availability of funds from CARB-X; the nomination of a final vaccine candidate for VAX-PG; the market opportunity for our vaccines; our expectations regarding the potential benefits, spectrum coverage and immunogenicity of our vaccine candidates; the timing of the initiation, progress and expected results of our preclinical studies, clinical trials and research and development plans; 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; Vaxcyte's reliance on third-party manufacturers; 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; sufficiency of cash and other funding to support Vaxcyte's development programs and other operating expenses; and the ongoing COVID-19 pandemic, 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 Quarterly Report on Form 10-Q filed with the SEC on November 10, 2021 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. о#33 Vaxcyte Mission Statement Vaxcyte Seeking to improve global health by developing superior & novel vaccines designed to prevent or treat some of the most common & deadly infectious diseases worldwide. о#44 Key Corporate Highlights Next-Generation Vaccine Company - Led by Pneumococcal Conjugate Vaccine (PCV) Franchise о Large Market Opportunity for PCV Franchise Protein Synthesis Cell-Free Platform Disciplined Target Selection • • Scalable PCV platform enabling broader-spectrum PCVS: VAX-24 & VAX-XP - Lead candidate: VAX-24 24-valent PCV with potential to replace SOC Anticipated IND filing in Q1:22(1) Anticipated Phase 1/2 data readout in late '22- early '23(1) (1) Guidance provided as of November 10, 2021. • Leverages site- specific conjugation • • Permits production of "tough-to-make" antigens Demonstrated speed, flexibility, and scalability . • Robust Development Pipeline Aligned Critical Resources Targets well-defined >$7B market segment Honors well- understood PCV MOA Leverages established surrogate immune • Platform unlocks large market opportunities: - VAX-A1: Novel Group A Strep conjugate vaccine VAX-PG: Novel periodontitis therapeutic endpoints and clinical pathways vaccine Strategic alignment with Lonza (manufacturing) Seasoned management team, directors and advisors • Cash, cash equivalents and investments of $318.3M at 9/30/21#5LO 5 Experienced Team, Board of Directors, and Scientific Advisors Outstanding Track Record in Vaccines and Biopharma о Andrew Guggenhime, MBA President & CFO Board of Directors Carlos Paya, MD, PhD Chair IMMUNE DESIGN Peter Hirth, PhD Plexxikon. Annie Drapeau ☐ toast moderna Michael Kamarck, PhD MERCK Wyeth Halley Gilbert NEO GENOMICS Teri Loxam SQZBIOTECH MERCK Management Team Grant Pickering, MBA CEO & Co-founder PROVENGE® (sipuleucel-T) +ZELNATE Victrio FLONASE ALLERGY RELIEF Jim Wassil, MS, MBA COO Prevnar 13 Pneumococcal 13-valent Conjugate vaccine (Diphtheria CRM Protein) BEXSERO® Meningococcal Group B Vaccine MENVEO RotaTeq Dermira Calistoga Pharmaceuticals Facet Biotech Heath Lukatch, PhD RED TREE VENTURE CAPITAL Kurt von Emster Abingworth partners in life science investing Grant Pickering Vaxcyte Jeff Fairman, PhD VP Research & Co-founder ZELNATE. T Victrió Paul Sauer, MBA SVP PD & Manufacturing Pulmozyme ●Pulmozy INHALATION SOLUTION Zinbryta (daclizumab) Harp Dhaliwal, MBA SVP Commercial Manufacturing & Supply Chain Dermira MEDIVATION Biogen Scientific Advisory Board Jeff Almond, PhD sanofi pasteur The vaccines division of sanofi-aventis Group Bill Hausdorff, PhD gsk ithin Wyeth GlaxoSmithKline Tony Ford-Hutchinson, PhD MERCK Tom Monath, MD CROZET BioPharma Emmanuel Hanon, PhD \IOME gsk GlaxoSmithKline Emmanuel Walter, MD, MPH Vaccines Duke University School of Medicine#6Next-Generation Vaccine Pipeline Focus on Superior PCV Franchise with Novel, Early Stage Pipeline to Follow VAX-24 VAX-XP VAX-A1 Lead Candidate 24-Valent PCV Next-Generation >30-Valent PCV Novel Group A Strep Vaccine TARGET INFANTS & ADULTS POPULATION • . Anticipate IND filing in Q1:22(1) • Anticipate Phase 1/2 data readout in the adult population in late '22-early '23(1) Published preclinical POC vs. PrevnarⓇ13 (PCV13) and PneumovaxⓇ23 (PPV23) in the journal Vaccine 6 (1) Guidance provided as of November 10, 2021. • INFANTS & ADULTS VAX-PG о Novel Therapeutic Periodontitis Vaccine CHILDREN & ADULTS ADULTS PCV13 • Initiated IND-enabling activities in 2H:21 • Anticipate selecting final vaccine candidate in 1H:22(1) ● Supported with grant from CARB-X Completed preclinical POC vs. and PPV23 Investing to maximize PCV franchise optionality and value#7Cell-Free Protein Synthesis Platform Unlocks Multiple Vaccine Applications Design and Produce Proteins Beyond Reach of Conventional Methods о XpressCF Platform (1) Cell-Free Protein Synthesis (CFPS): • • Transcriptional & translational (ribosomal) machinery from E coli stored as a frozen “extract" Produces singular protein of interest at high yields Uniquely enables site-specific conjugation via insertion of multiple nnAA conjugation anchors Uniquely permits protein production in non- physiological conditions Speed, Flexibility, Scalability: Cell free extract Temp + Redox Potential MM Adjustable Reaction Conditions pH • Rapidly screen vaccine candidates Flexible reaction conditions Scaled to 1000L using standard equipment 7 (1) Exclusively licensed from Sutro Biopharma for the field of vaccines addressing infectious diseases. Conjugation Anchors Platform Capabilities 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 Designed to enable use of less protein carrier without sacrificing immunogenicity • Enables 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#8Vaxcyte PCV Opportunity#9Global Impact of Pneumococcal Disease Remains Significant о About Streptococcus Pneumoniae Streptococcus pneumoniae is the most common pathogen causing pneumococcal disease (PD). Global Incidence and Impact of PD Global incidence of PD is driven by emerging serotypes not covered by currently available vaccines. Current Global Standard-of-Care (SOC) Vaccinations are recommended globally for infants and adults to prevent PD. Non-invasive PD includes: otitis media, sinusitis, pneumonia. Invasive PD (IPD) includes: bacteremia, meningitis. Pneumococci cause over 50% of all cases of bacterial meningitis in the U.S. In the U.S. alone, there are ~900K pneumococcal pneumonia cases annually. For IPD, adult mortality rates in the U.S. range from 11% to 30%. Among children under age 5, PD is a leading cause of death globally. In the U.S.: Infants: PCV13 (4 doses) Adults: Prevnar 20 TM (PCV20) (1 dose) or Vaxneuvance TM (PCV15) and Pneumovax 23Ⓡ (PPV23) (1 dose/each) 6 1 Gierke 2015 2 https://www.cdc.gov/abcs/reports-findings/survreports/spneu 18.pdf CDC 2018 https://www.cdc.gov/pneumococcal/clinicians/clinical-features.html#10110 Significant Unmet Needs Remain Despite SOC Today Resulting in Spectrum of Coverage Driving Adoption of Pneumococcal vaccines Estimated coverage of PCVs based on circulating invasive pneumococcal serotypes. 100 90 Percent Coverage of IPD 1 Data in the US is for 2017, inclusive of those > 5 yrs of age 2Varghese et al. Clin Micro and Infect (2020) 26(4): 512.e1-512.e10 VAX-XP 80 70 VAX-24 60 50 PCV20 40 PCV15 30 20 10 PCV13 0 US Adult Most disease caused by strains above and beyond Prevnar 13Ⓡ, driving need for broader- spectrum PCVS. о#11Serotype 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 Cases Per 100,000 UK IPD Cases in Adults > 65 (1) Prevnar 13 Types Non-vaccine Types (1) Ladhani et al, Lancet Infect Dis 2018 Apr;18(4):441-45 inclusive of unpublished raw data. 30 25 20 15 10 5 0 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 11 2016 Residual disease driven by incremental 11 strains over and above PCV13. PCV13 highly effective in prevention of invasive PD and circulation of included strains. о#1212 Vaxcyte PCV Franchise Designed to Offer Broader Protection Potential for Sustained Leadership in the Established >$7B Pneumococcal Vaccine Market VAX-24: Category-leading 24-valent PCV incorporating carrier-sparing conjugates о VAX-XP: Next-generation >30-valent PCV showcases franchise approach and scalability of carrier-sparing conjugates 6B 9V 14 18C 19F 23F 1 5 7F 3 6A 19A 33F 22F 8 10A 11A 12F 15B 2 9N 17F 20 A B C D Prevnar Synflorix Prevnar 13 Madaga More Vaxneuvance" Pneumococcal 15-valent Prevnar 20™ Pneumococcal 20-valent Conjugate Vaccine PNEUMOVAX23 VAX-24 VAX-XP Source: Prescribing information for Prevnar, Prevnar 13, Prevnar20, Synflorix, Vaxneuvance, and Prevnar 20. Company filings for Vaxcyte LU E LL F G H | J TBD Spectrum of Coverage Drives Adoption#13Pneumococcal Vaccine Market is Highly Attractive VAX-24 has the Potential to Become the Most Broad-Spectrum PCV Pneumococcal Vaccine Market Dynamics • • Spectrum of coverage drives adoption Highly attractive margins: - Prevnar 13 & Pneumovax 23 are premium priced in the US Durable revenue stream: - Prevnar 13 & Pneumovax have generated >$100B in revenues PCVs are best-in-class: Well-understood T-cell dependent MOA tied to co-presentation of disease-specific polysaccharide antigens with mapped T-cell epitopes on protein carrier Well-defined clinical development path: Non-inferiority to SOC using validated surrogate immune endpoints now adequate for full approval for follow-on PCVS Potential for rapid adoption: Governing body - ACIP recommendation drives uptake - Prevnar 13 vs Prevnar 7 - ShingrixⓇ vs ZostavaxⓇ MOA = mechanism of action; SOC = standard of care; ACIP = US CDC Advisory Committee on Immunization Practices. (1) Revenues reported in GSK (Shingrix) and Merck (Zostavax) financial filings. 13 ($Billions) SHINGRIX HERPES ZOSTER VACCINE NON-LIVE RECOMBINANT, ASOI, ADJUVANTED) $3.0 ■Zostavax Shingrix (1) $2.5 $2.0 $1.5 $1.0 $0.5 $0.0 2017 2018 2019 2020 • FDA Approved in 4Q:2017 to prevent shingles in adults • ACIP granted “preferred recommendation" • Replaced the incumbent (Zostavax from Merck) о#14Potential for Global Pneumococcal Market to Grow Beyond the $7B Today о The Oct. 2021 ACIP Vote Reinforced Need for PCVs with Broader Spectrum of Coverage and for Use in Expanded Adult Population ➤ ACIP supported use of either Pfizer's PCV20 or Merck's PCV15 plus Pneumovax23 in adults ≥65 years of age By preserving PPV23, ACIP decision reinforces the need for a 24-valent PCV ➤ Age-based recommendation remains at age 65, per ACIP This is the first time ACIP has recommended a PCV for risk groups ages 19 to 64 Significantly expands adult population and increases overall PCV market ➤ Strong desire expressed by several ACIP committee members to move adult vaccination to 50 years of age CDC committed to gathering more data and revisiting at a future meeting Provides important opportunity to address unmet needs in adults#1515 PCVs Overcome the Limitations of Polysaccharide-Only Vaccines PCV Efficacy Driven by T-Cell Epitopes on Diphtheria Toxin Protein Carrier - CRM 197 (1) Polysaccharide YYX PS-Only Vaccine PNEUMOVAX23 Independent B cells Antibody (no memory) B cell T-Cell Dependent Conjugated protein Prevnar 13 PCVs Pneumococcal 13-vdent Conjugate Vaccine Diphtheria CRM, Protein) Synflorix ON Target Effect B Cells Targeting Polysaccharide T Cell 83 T Cells T-cell help Fi イイ Antibody + memory • Broad Coverage But Limited Protection in Adults - Not Boostable - B Cells Targeting Protein Carrier OFF Target Effect イイ Narrow Coverage But Highly Effective in Adults & Infants - Boostable - Pneumococcal capsular polysaccharides (PS) antigens lead to: • - Transient Ab responses (IgM) protect against sepsis, but not pneumonia No T-cell mediated memory responses, thus no boost Hyporesponsive effect inhibits ability to boost PCVs post-prime Note: Graphics adapted from Strugnell et al, Understanding Modern Vaccines, Vol 1, Issue 1, 61-88. (1) Protein carrier in Prevnar 13 is a modified form of diphtheria toxin (CRM 197). Conjugation of PS to protein carrier leads to: Enhanced Ab responses (IgG) that protect against pneumonia - T cell-mediated memory to provide boostable, durable protection Characteristic interstrand crosslinked matrix-like structures о#16Limitations of Current PCVS Coverage Expansion Needed to Address Circulating Disease, but Protein Carrier Backbone Problematic о 60 60 50 40 40 30 30 Limitations of Conventional Chemistry Random conjugation Higher ratio of protein carrier to polysaccharide Further exacerbates carrier suppression Protein Carrier (ug) ■Serotype Coverage (#) 34 51 554 10 210 20 20 20 20v 13v 7v 0 Prevnar 7 Prevnar 13 Pfizer 20v 16 (1) Prevnar 20 BLA Clinical Review Memorandum. STN: 125731/0 June 8, 2021.#1717 (2) IgG Titers Limitations of Current PCVS Coverage Expansion Using Conventional Chemistry Has Led to Carrier-Induced Immune Suppression • - Carrier Suppression Reduced immune response to the target polysaccharides due to the cumulative amount of the protein carrier Expanded spectrum of coverage requires increasing protein carrier burden Reduced immune responses demonstrated in both infants and adults о Infant Immune Responses (IgG): Prevnar 7 vs Prevnar 13 (1) Adult Immune Responses (OPA): Prevnar 13 vs PCV20 (2) 33% PCV7 IPCV13 6 % Drop 32% 30% 30% 2000 24% 25% 35% PCV13 PCV20 % Drop 30% 20% 20% 20% LO 19% 20% 1500 17% 17% 23% 17% 16 25% 16% 156 15% 14% 15% T 20% 1000 15% 10% N L 10% 500 5% 1 5% 0 0% 0 0% 4 6B 23F 9V 18C 19F 14 6A 1 19A 19F 4 6B 23F 5 18C 3 7F 9V 14 (1) Yeh et al, Pediatrics. 126: e493 (2010). Prevnar 20 BLA Clinical Review Memorandum. STN: 125731/0 June 8, 2021 % Drop PCV 20/PCV 13#18Vaxcyte Differentiated PCV Franchise Led by VAX-24#19VAX-24 Employs Carrier-Sparing Conjugates XpressCF Enables Precise Conjugation to Enhance Potency of Standard Protein Carrier 19 19 Precise, Site-Specific Conjugation Sites on Proprietary eCRM® Protein Carrier Illustrative nnAA Conjugation Anchors (red) 500 Avoid T-cell Epitope Regions (pink) о Final VAX-24 Conjugates in Customary Matrix Form eCRM: Enhanced Potency Potential • Avoids masking sites on CRM 197 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-24 and VAX-XP conjugates form standard PCV interstrand crosslinked matrices - Perceived as foreign by the host Allows use of standard critical quality attribute & serological assays#2020 20 VAX-24 Design Leverages Many Standard PCV Conventions Utilizes Proven Components, Chemistries and Assays to Reduce Risk and Uncertainty Pfizer/GSK Methods Vaxcyte Polysaccharide Protein Carrier CDAP / Periodate Activation Amination for labeling PS Incorporation of non-natural AAs Random Lysine Conjugation Site-Specific Click Chemistry Conjugation Novel Enablement: Site-specific conjugation via incorporation of nnAA conjugation anchors Assays CQA Release Assays (Mol Wt, Free PS) Serological Assays (IgG & OPA) о • Where appropriate, we expect to capitalize on the efficiencies of well-established clinical, manufacturing & regulatory precedents by leveraging conventional methods for the development of VAX-24 . Vaxcyte has leveraged the same animal models utilized in the development of both approved PCVs (Prevnar and Synflorix)#21VAX-24 Preclinical POC Study Designed to Assess Conjugate-Like Immune Responses vs Standard of Care 21 21 Study Design: Vaccination of rabbits (1) with doses matching weight-to-weight allometric scaling to marketed human dose Preclinical POC Study: Rabbits (n=10/cohort) Dosed at Day 0 & Day 21 Randomize (1:1:1) VAX-24(2) @ 0.11μg PS / conjugate Prevnar 13 @ 0.11µg PS / conjugate(3) Pneumovax 23 @ 1.1μg PS OPA (4) & IgG Immune Responses: VAX-24 vs Prevnar 13 (common 13 strains) VAX-24 vs Pneumovax 23 (common 23 strains) Prime Prime Dose Dose Immunogenicity Assessment Boost Dose Day 0 Day 14 Day 21 Key Endpoints: Boost Dose Immunogenicity Assessment Day 35 Key Objectives: Demonstrate conjugate-like responses vs SOC on all 24 serotypes • OPA Responses: Primary surrogate endpoint for full approval in adults IgG Responses: Co-Primary surrogate endpoint for full approval in infants Immunogenicity (OPA & IgG) VAX-24 vs Prevnar 13 common serotypes (Day 35) VAX-24 vs Pneumovax 23 for 11 incremental serotypes (Day 35) (1) Represents same rabbit model as utilized in the development of approved PCVs (Prevnar, Prevnar 13, Synflorix). (2) VAX-24 conjugates produced with all Lonza-produced materials (eCRM & 24 polysaccharides) (3) Prevnar 13 dose of 6B is 2x the amount relative to the other conjugates, so equates to 0.22ug in this study. (4) Opsonophagocytic activity assay (OPA) measures the functional capacities of vaccine-candidate-raised antibodies. о#2222 22 VAX-24 Preclinical POC Study Supports Potential to Deliver Broader-Spectrum PCV IgG Antibody Titer Comparisons (Current Standard for Approval in Pediatrics) о ❖ Comparable or better immune responses for VAX-24 relative to Prevnar 13 and Pneumovax 23 across common strains. Potential for approval in pediatrics based on non-inferiority relative to standard of care (≥ 50% of IgG titers one month post-boost). IgG Titer 1 × 105 13 Serotypes in Prevnar & Pneumovax 1×104 1 x 103 1x102 1 × 10 1 T T 1 × 10° 3 Note: +/-95% confidence interval. 4 5 6A 6 B 7F 9V ・カレ 0.11ug VAX-24 18C 19A 19F 23F 2 00 N6 11 Serotypes in Pneumovax 10A- 11A - 0.11ug Prevnar 13 1.1ug Pneumovax 23 12F 15B 17F 20. 22F 33F#23VAX-24 Preclinical POC Study Supports Potential to Deliver Broader-Spectrum PCV Functional Antibody (OPA) Responses (Current Standard for Approval in Adults) о 1 × 105 ✰ Comparable or better immune responses for VAX-24 relative to Prevnar 13 and Pneumovax 23 across all common strains. ❖ Potential for approval in adults based on non-inferiority relative to standard of care (≥ 50% of OPA titers one month post- vaccination). 13 Serotypes in Prevnar & Pneumovax 11 Serotypes in Pneumovax OPA Titer 1 × 10 4 1 × 10 3 1x102. 1 × 10 1 1 × 10° T --- --חשון Note: +/-95% confidence interval. 23 T 3 4 5 6A. 6B 7F A6 ・セレ 0.11ug VAX-24 18C 19A 19F 23F 0.11ug Prevnar 13 2 8 N6 1.1ug Pneumovax 23 10A- 11A- 12F- 15B 17F- 20- 22F 33F#2424 24 VAX-XP: Further Evidence of Potential for Platform Scalability IgG Responses for VAX-XP Comparable to Prevnar 13 & Superior to Polysaccharide-only Serotypes ❖ VAX-XP incorporates VAX-24 strains plus emerging serotypes responsible for significant IPD & antibiotic resistance. * Demonstrates spectra scalability of platform and reproducibility of VAX-XP POC data with conjugates produced at larger scale. 13 Serotypes in Prevnar 13 & Pneumovax 23 11 Serotypes in Pneumovax 23 7 additional XP Serotypes IgG Titer 1 × 104 1 × 10 3 1x102 1 x 101 T 1 × 10º 34 Note: +/-95% confidential interval. 5 (1) VAX-XP, includes all 24 strains in VAX-24 and 7 additional pneumococcal conjugates. (2) PS/Alum = PSs formulated with alum. 6A 6B 7F 9V 14 18C 19A 19F 23F 8 N6 0.11ug VAX-XP 10A 11A 12F 15B 17F 20 22F 33F 0.11ug Prevnar 13 1.1ug PS/Alum#2524 24 PCV Franchise Leverages Established Regulatory Pathway о Potential FDA Approval Path Supported by Current WHO Guidance & Precedent PCVs Well-defined, validated surrogate immune endpoints = no anticipated requirement for field efficacy trials Demonstration of non-inferior (≥50%)(1) immune responses vs. SOC consistent with Merck (V114) and Pfizer (PCV20) BLA filings (2)(3) Surrogate immune endpoints (4)(5)(6) have been consistent between Ph 2 POC and Ph 3 pivotal studies for adult and infant programs Anticipate VAX-24 IND filing in Q1:22 with Phase 1/2 clinical topline data readout in late '22-early '23(7) Pre-IND FDA meeting completed (Dec 2019) Vaxcyte's Approach for VAX-24 Ph 2 clinical POC study to include ~800 healthy adults aged 50-64 Potential for Fast Track, Priority Review and Breakthrough Designation (1) (2) (3) (4) (5) 95% CI lower limit of the OPA GMT ratio ≥0.5 for each serotype comparison. Clinicaltrials.gov: Pfizer clinical studies for 20vPnC NCT03512288, NCT03550313, NCT03313050, NCT03313037, NCT03760146, NCT03835975, and NCT03828617. Clinicaltrials.gov: Merck clinical studies for V114 (PCV15) NCT02987972, NCT03620162, NCT03692871, NCT03731182, NCT03480763, NCT03615482, NCT03547167, NCT03480802, and NCT03565900. WHO. Recommendations to assure the quality, safety and efficacy of pneumococcal conjugate vaccines, in WHO Expert Committee on Biological Standardization, 60th report. Geneva, Switzerland: WHO; 2013:91-521. Prevenar 13 FDA Summary Basis for Regulatory Action. BLA/STN: 125324, 2010. ttps://www.fda.gov/downloads/Biologics Blood Vaccines/Vaccines/Approved Products/UCM206140.pdf. Accessed January 10, 2020. (6) Guidelines on clinical evaluation of vaccines. EMEA/CHMP/VWP/164653/05, April 2018. https://www.ema.europa.eu/en/documents/scientific-guideline/draft-guideline-clinical-evaluation-vaccines-revision-1_en.pdf, Accessed Feb 11, 2020. (7) Guidance provided as of November 10, 2021.#2626 VAX-24 Phase 1/2 Clinical Proof-of-Concept Study Designed to Demonstrate Non-Inferiority to SOC on Approvable Endpoint in Adults (OPA) о Study Design: Randomized, Observer-Blind, Dose-Finding, Controlled Study to Evaluate Safety & Immunogenicity of VAX-24 in Adults Screen and Randomize Pilot Safety Healthy Adults 18 to 49 (n-64) DMC Review Safety Follow- Up(1) Screen Randomize (1:1:1:1) VAX-24 Low Dose VAX-24 Middle Dose VAX-24 Mixed Dose Clinical POC Study Healthy Adults 50 to 64 (n-800) IgG & OPA VAX-24 VS Prevnar 20 (common 20 strains) Safety Follow- Up Final Safety Assessment Dose Day 0 Day 8 Day 29 Month 6 Day 0 Key Objectives: • Evaluate safety & tolerability of single injection of VAX-24 in healthy adults 18 to 49 yrs (n~64) Comparative safety & tolerability of 3 different dose . formulations of VAX-24 in healthy adults 50 to 64 yrs versus Prevnar 20 (1) Pilot Safety Follow-up will continue thru Day 212 in parallel upon initiation of Clinical POC Study after Day 29 safety observation. Prevnar 20 Dose Key Endpoints: • Blood Sample Day 29 Immunogenicity Assessment Month 6 Immunogenicity (OPA & IgG) - VAX-24 vs Prevnar 20 common serotypes - VAX-24 incremental 4 serotypes not in Prevnar 20 GMT 4-fold rise 50 to 64 yr old cohort powered at >85% to detect OPA response of ≥50% across treatment groups & dose cohorts on a per serotype basis#27Critical Manufacturing Foundation Established for PCV Franchise Designed to Provide Robust & Scalable Capacity to Independently Supply Market 27 27 Strategic Alignment with Best-in-Class CDMO Lonza + Overview / Structure: • • End-to-end "turnkey" supply established at marquee Swiss facility Fee-for-service relationship with risk sharing to align the parties Status: • • · • • • • Manufactured, tested and released GMP critical raw materials (eCRMⓇ & 24 polysaccharides) Manufactured, tested and released the 24 GMP conjugated drug substances (DS) Completed GMP drug product (DP) manufacture (formulation, fill and finish) Anticipated completion of remaining DP testing and release, as well as documentation of stability, is expected prior to IND application filing and supply for VAX-24 Phase 1/2 clinical development Commercial production capacity available at same site using existing infrastructure or Ibex capacity coming on-line Exclusive License to Cell-Free Protein Synthesis Platform SUTRO BIOPHARMA Exclusive, worldwide, royalty-bearing, sub-licensable license for field of vaccines to treat or prevent infectious disease (4% royalty) Sutro Biopharma source of cell-free extract and custom reagents VAX-24 Manufacturing Process / Status Dev Campaign GMP eCRM Campaign Dev Campaign Dev Campaign GMP Conjugate Campaign x 24 GMP Polysaccharide Campaign x 24 Formulation/Fill/Finish VAX-24 Drug Product Testing & Release о#2828 The Pneumococcal Vaccine Landscape Vaxcyte PCV Franchise Designed to Offer Broadest Spectrum of Coverage PCV Approaches DEVELOPER VACCINE NAME SPECTRUM OF COVERAGE GSK SYNFLORIX 10-VALENT VAXNEUVANCE MERCK MERCK V116 MERCK V117 UNKNOWN PREVNAR 13 PFIZER PREVNAR 20 SK BIOSCIENCE / SANOFI-PASTEUR TBD VAX-24 VAXCYTE (SITE-SPECIFIC CONJUGATION) VAX-XP TBD 15-VALENT 13-VALENT STATUS TARGET POPULATION: INFANTS ADULTS APPROVED EX-US FDA APPROVED IN ADULTS PHASE 3 IN INFANTS 21-VALENT • PRECLINICAL 20-VALENT PRECLINICAL SOC IN INFANTS AND ADULTS FDA APPROVED IN ADULTS PHASE 3 IN INFANTS PH 1/2 IN ADULTS 24-VALENT 30 PLUS- VALENT IND-ENABLING PRECLINICAL POC (SITE-SPECIFIC CONJUGATION) Non-PCV Approaches MERCK 23-VALENT PNEUMOVAX 23 (PS ONLY) SOC IN ADULTS POST- PCV13 AFFINIVAX / ASTELLAS ASP3772 (AFFINITY-BOUND PSS TO NOVEL PNEUMO PROTEINS) 24-VALENT PHASE 1/2 IN ADULTS о SOC standard of care; PS = polysaccharides,#29Vaxcyte Non-PCV Pipeline#3030 50 VAX-A1: Group A Strep Conjugate Vaccine Program Monovalent Conjugate Vaccine Designed to Provide Universal Protection о Unmet Need VAX-A1: Broad-spectrum, Monovalent Conjugate Vx Program Status Group A Strep causes 700M global annual cases of pharyngitis (strep throat) and increases risk of severe invasive infections such as sepsis, necrotizing fasciitis and toxic shock syndrome • Upgraded CDC threat given significant source of antibiotic Rxs driving resistance which has nearly tripled in past decade Responsible for post-infectious immune-mediated rheumatic heart disease leading to over 300K deaths in 2015 • Highly prevalent in children and rate of invasive disease in adults > 65 has more than doubled (exceeding IPD rate in adults) 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 Partially funded by grant from CARB-X (consortium of BMGF, Wellcome Trust, US Biodefense Agency (BARDA)); add'l August 2021 award of $3.2M toward IND-enabling activities; total potential funding of up to $29.7M inclusive of grants to date • Nominated final vaccine candidate in 1Q 2021 Initiated IND-enabling activities in 2H 2021 25- © 20 Resistance tripled over past decade 100 80- " Active immunization Mock - - SLO + C5a pep Key Data BMGF = Bill & Melinda Gates Foundation. % Resistance 15 10- CDC. Antibiotic Resistance Threats in the United States, 2019. Atlanta, GA: US Department of Health an 20 2013 5 2010 2011 2014 Services, 2015 CBC 202016 2017 Percent survival 60 L 40 20 0 0 24 48 72 Time (h) 96 120 - SpyAD-GACPR VAX-A1 (SLO + C5a pep + SpyAD-GACPR)#31VAX-PG: Periodontitis Vaccine Program Therapeutic Vaccine Targeting Gingipains to Address Large, Underserved Market о Unmet Need VAX-PG: Multivalent Therapeutic Vaccine Program Status Periodontal disease is a chronic oral inflammatory disease leading to destruction of soft & hard tissues supporting the teeth Highly prevalent: 65 million US adults afflicted • Significant morbidity and lost productivity: >$50B in lost productivity in 2010 Associated with increased risk of heart attack, stroke, cardiovascular disease, and Alzheimer's Disease • Incorporates proprietary combination of known virulence factors of keystone pathogen • Preclinical model demonstrated protein-specific IgG response following immunization and protected mice from P. gingivalis- elicited oral bone loss Initial goal to develop therapeutic vaccine that slows or stops disease progression Preclinical proof of concept published in Journal of Clinical Periodontology Next milestone: Nominate final vaccine candidate in 1H 2022(1) MOA & Key Data Restoration of balanced microbiota by interrupting underlying inflammatory condition A. viscosus Pgingivalis * 伞 Sall HA1 P. gingivalis MFA1 Gingival epithelial cells Sgordan ABC to CEJ Length (mm) 0.251 0.20- 0.15- 0.10. - control No Vaccine + control VAX-PG/Alum VAX-PG/MPL VAX-PG Challenge Study Results Immunization with all formulations of VAX-PG provided significant protection against oral bone loss compared to the unvaccinated control (p<0.01) (1) Guidance provided as of November 10, 2021. 31 Huang et.al. J Clin Periodontol. 2019 Feb;46(2):197-205#3232 32 Key Corporate Highlights Next-Generation Vaccine Company Vaxcyte Large Market Opportunity for Lead PCV Franchise Cell-Free Protein Synthesis Platform Disciplined Target Selection Robust Pipeline with Multiple Novel Vaccines Aligned Critical Resources о