8-K

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): October 24, 2022

Vaxcyte, Inc.

(Exact name of Registrant as Specified in Its Charter)

Delaware	01-39323	46-4233385
(State or Other Jurisdiction of Incorporation)	(Commission File Number)	(IRS Employer Identification No.)

825 Industrial Road
Suite 300
San Carlos, California	94070
(Address of Principal Executive Offices)	(Zip Code)

Registrant’s Telephone Number, Including Area Code: 650 837-0111

Not Applicable

(Former Name or Former Address, if Changed Since Last Report)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

☐ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

☐ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

☐ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

☐ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:

Title of each class	Trading Symbol(s)	Name of each exchange on which registered
Common Stock, $0.001 par value per share	PCVX	The Nasdaq Stock Market LLC

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).

Emerging growth company ☐

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

Item 8.01 Other Events.

On October 24, 2022, Vaxcyte, Inc. (“Vaxcyte”) issued a press release announcing topline data from its Phase 1/2 proof-of-concept study evaluating VAX-24, Vaxcyte’s investigational 24-valent pneumococcal conjugate vaccine for the prevention of invasive pneumococcal disease (IPD), in healthy adults aged 18 to 64. The topline data includes the safety and tolerability results from the Phase 1 portion of the study and safety, tolerability and immunogenicity results from the Phase 2 portion of the study. The press release is attached hereto as Exhibit 99.1 to this Current Report on Form 8-K and is incorporated herein by reference.

On October 24, 2022, Vaxcyte also made available the slide presentation attached as Exhibit 99.2 to this Current Report on Form 8-K and is incorporated herein by reference.

Item 9.01 Financial Statements and Exhibits.

(d) Exhibits

Exhibit Number	Description
99.1	Press Release, dated October 24, 2022.
99.2	Slide presentation, dated October 24, 2022.
104	Cover Page Interactive Data File (embedded within the Inline XBRL document)

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned thereunto duly authorized.

Date:     October 24, 2022	By:	/s/ Andrew Guggenhime
		Andrew Guggenhime President and Chief Financial Officer

EX-99.1

Exhibit 99.1

Vaxcyte Reports Positive Topline Data from Phase 1/2 Proof-of-Concept Study of its 24-Valent Pneumococcal Conjugate Vaccine Candidate Being Investigated for the Prevention of Invasive Pneumococcal Disease in Adults Aged 18-64

— In the Study, VAX-24 Demonstrated a Safety and Tolerability Profile Similar to Prevnar 20^TM (PCV20) at All Doses Studied —

— All 24 Serotypes of VAX-24 at Conventional 2.2mcg PCV Dose Met or Exceeded Regulatory Immunogenicity Standards —

— All 20 VAX-24 Serotypes Common with PCV20 Met Standard OPA Response Non-Inferiority Criteria, of Which 16 Achieved Higher Immune Responses, at 2.2mcg VAX-24 Dose —

— All 4 Serotypes Unique to VAX-24 Exceeded Standard Superiority Criteria —

— Vaxcyte to Advance Potential Best-in-Class VAX-24 Clinical Program in Adult and Pediatric Populations —

— Company to Host Webcast/Conference Call Today at 8:00 a.m. ET / 5:00 a.m. PT —

SAN CARLOS, Calif., October 24, 2022 – Vaxcyte, Inc. (Nasdaq: PCVX), a clinical-stage vaccine innovation company engineering high-fidelity vaccines to protect humankind from the consequences of bacterial diseases, today announced positive topline results from the Phase 1/2 clinical proof-of-concept study evaluating the safety, tolerability and immunogenicity of VAX-24, the Company’s investigational 24-valent pneumococcal conjugate vaccine (PCV), in healthy adults aged 18-64. In this study, VAX-24 met the primary safety and tolerability objectives, demonstrating a safety profile similar to Prevnar 20^TM (PCV20) for all doses studied.

In the study, VAX-24 met or exceeded the established regulatory immunogenicity standards for all 24 serotypes at the conventional 2.2mcg dose, which the Company intends to move forward into a Phase 3 program. At this dose, VAX-24 met the standard opsonophagocytic activity (OPA) response non-inferiority criteria for all 20 serotypes common with PCV20, of which 16 achieved higher immune responses. Additionally, at all three doses, VAX-24 met the standard superiority criteria for all four serotypes unique to VAX-24. These four incremental serotypes cover 10-15 percent of strains causing invasive pneumococcal disease (IPD) over the current standard-of-care in adults.

“We are thrilled with these positive topline results from our Phase 1/2 proof-of-concept study, which met all of our objectives. The findings indicate a potential best-in-class profile for VAX-24 and validate our carrier-sparing approach to enable the development of broader-spectrum PCVs,” said Grant Pickering, Chief Executive Officer and Co-Founder of Vaxcyte. “The study results demonstrate that VAX-24 has the potential to provide broader coverage and better immune responses relative to the standard-of-care. We believe this presents an opportunity to set a new bar for immunogenicity standards for pneumococcal vaccines.”

Key Topline Study Results

Safety and Tolerability Findings:

• VAX-24 demonstrated a safety and tolerability profile similar to PCV20 at all doses studied.

• Frequently reported local and systemic reactions were generally mild-to-moderate, resolving within several days of vaccination, with no difference observed across the cohorts. No serious adverse events or new onset chronic illnesses were considered to be related to study vaccines.

• The full six-month safety follow-up is ongoing for the Phase 2 portion of the study.

Immunogenicity Findings:

• VAX-24 demonstrated robust OPA and immunoglobulin G (IgG) immune responses for all 24 serotypes at all doses studied (1.1mcg, 2.2mcg, 2.2mcg/4.4mcg), each of which could advance into Phase 3.

• The VAX-24 2.2mcg dose met or exceeded the established regulatory immunogenicity standards for all 24 serotypes and is the dose the Company expects to advance into Phase 3.

• At the 2.2mcg dose, VAX-24 met the standard OPA response non-inferiority criteria⁽¹⁾ for all 20 serotypes common with PCV20, of which 16 serotypes (3, 4, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 23F and 33F) achieved higher immune responses and four serotypes (9V, 18C, 19F and 33F) reached statistical significance.

• At all three doses, VAX-24 met the standard superiority criteria⁽²⁾ for all four serotypes (2, 9N, 17F and 20B) unique to VAX-24.

“We are very excited to share these strong clinical results from our proof-of-concept study, which validate the potential for VAX-24 to improve upon the standard-of-care for adults by potentially providing 10-15 percent incremental protection for this serious disease. The 24 serotypes included in VAX-24 cover a significant portion of the IPD currently in circulation and are associated with high case-fatality rates, antibiotic resistance and meningitis,” said Jim Wassil, Executive Vice President and Chief Operating Officer of Vaxcyte. “On behalf of our team at Vaxcyte, we would like to gratefully acknowledge the efforts of everyone involved in this program, especially the trial investigators, trial sites and study participants.”

About the Phase 1/2 Clinical Proof-of-Concept Study

The VAX-24 Phase 1/2 clinical proof-of-concept study is a randomized, observer-blind, dose-finding, controlled study designed to evaluate the safety, tolerability and immunogenicity of VAX-24 in healthy adults 18-64 years of age.

The Phase 1 portion of the study evaluated the safety and tolerability of a single injection of VAX-24 at three dose levels, 1.1mcg, 2.2mcg and 2.2mcg/4.4mcg, and compared to PCV20 in 64 healthy adults 18 to 49 years of age.

The Phase 2 portion evaluated the safety, tolerability and immunogenicity of a single injection of VAX-24 at the same three dose levels and compared to a single injection of PCV20 in 771 healthy adults 50 to 64 years of age. The immunogenicity objectives of the Phase 2 portion of the study include an assessment of the induction of antibody responses, using OPA and IgG, at each of the three VAX-24 doses and compared to PCV20, and for the additional four serotypes contained in VAX-24 (and Pneumovax^® 23), but not in PCV20, the percentage of subjects that experience a four-fold rise in antibody titers. Participants in the study will be evaluated for safety through six months after vaccination. Additional information about the study can be found at www.clinicaltrials.gov under the identifier NCT05266456.

Key Anticipated PCV Franchise Milestones

Vaxcyte is advancing the clinical development of its PCV programs with several anticipated key milestones, including:

VAX-24 Adult Program

• Topline safety, tolerability and immunogenicity data from the Phase 2 study in adults 65 and older are anticipated in the first half of 2023.

• Final results with the 6-month safety data of the Phase 2 adult studies are anticipated in the first half of 2023.

• Regulatory interactions to inform the Phase 3 program are anticipated in the second half of 2023.

• Topline safety, tolerability and immunogenicity data from the Phase 3 non-inferiority study in adults are expected in 2025.

VAX-24 Pediatric Program

• The infant Investigational New Drug (IND) application submission and the Phase 2 study initiation are both anticipated in first half of 2023.

• Topline safety, tolerability and immunogenicity data from the infant Phase 2 study primary 3-dose immunization series are expected by 2025.

VAX-XP Adult Program

• The IND application submission for VAX-XP, Vaxcyte’s PCV candidate with 31 strains, is anticipated in the second half of 2023.

• Topline safety, tolerability and immunogenicity data from a Phase 1/2 study in adults are expected in 2024.

Conference Call and Webcast

Vaxcyte will hold a webcast and conference call today, Monday, October 24 at 8:00 AM ET to provide topline results from its VAX-24 Phase 1/2 proof-of-concept study. Those who would like

to participate may access the live webcast here, or register in advance for the teleconference here. A live webcast of the conference call will also be available on the investor relations page of the Vaxcyte corporate website at www.vaxcyte.com. After the live webcast, the event will remain archived on the Vaxcyte website for 30 days.

About VAX-24

VAX-24 is an investigational 24-valent PCV candidate designed to prevent IPD, which can be most serious for infants, young children, older adults and those with immune deficiencies or certain chronic health conditions. The public health community continues to affirm the need for vaccines that offer broader protection to prevent IPD. VAX-24 is intended to improve upon the standard-of-care PCVs for both children and adults by covering the serotypes that are responsible for most of the pneumococcal disease currently in circulation. Vaxcyte aims to efficiently create and deliver high-fidelity, broad-spectrum vaccines, such as VAX-24, by using modern synthetic techniques, including advanced chemistry and the XpressCF^TM cell-free protein synthesis platform. Vaxcyte is deploying this approach with VAX-24 in order to add more pneumococcal strains without compromising the overall immune response.

In August 2022, the FDA granted Fast Track Designation to VAX-24 for the adult indication. The Fast Track designation is an FDA process that has been designed to expedite the development and review of drugs, including vaccines, that treat or prevent serious conditions and fill an important unmet medical need.

About Pneumococcal Disease

Pneumococcal disease (PD) is an infection caused by Streptococcus pneumoniae (pneumococcus) bacteria. It can result in IPD, including meningitis and bacteremia, and non-invasive PD, including pneumonia, otitis media and sinusitis. In the United States, approximately 900,000 people get pneumococcal pneumonia each year, which is estimated to result in approximately 150,000 hospitalizations and 28,000 deaths. Pneumococci also cause over 50% of all cases of bacterial meningitis in the United States. Antibiotics are used to treat pneumococcal disease, but some strains of the bacteria have developed resistance to treatments. The morbidity and mortality due to pneumococcal disease are highly significant, particularly for young children and older adults, underscoring the need for a more broad-spectrum vaccine.

About Vaxcyte

Vaxcyte is a vaccine innovation company engineering high-fidelity vaccines to protect humankind from the consequences of bacterial diseases. The Company is developing broad-spectrum conjugate and novel protein vaccines to prevent or treat bacterial infectious diseases. Vaxcyte’s lead candidate, VAX-24, is a 24-valent, broad-spectrum pneumococcal conjugate vaccine being developed for the prevention of IPD. Vaxcyte is re-engineering the way highly complex vaccines are made through modern synthetic techniques, including advanced chemistry and the XpressCF^TM cell-free protein synthesis platform, exclusively licensed from Sutro Biopharma, Inc. Unlike conventional cell-based approaches, the Company’s system for producing difficult-to-make proteins and antigens is intended to accelerate its ability to

efficiently create and deliver high-fidelity vaccines with enhanced immunological benefits. Vaxcyte’s pipeline also includes VAX-XP, a PCV with coverage of 31 strains; VAX-A1, a prophylactic vaccine candidate designed to prevent Group A Strep infections; and VAX-PG, a therapeutic vaccine candidate designed to slow or stop the progression of periodontal disease. Vaxcyte is driven to eradicate or treat invasive bacterial infections, which have serious and costly health consequences when left unchecked. For more information, visit www.vaxcyte.com.

Forward-Looking Statements

This press release 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 VAX-24, including breadth of coverage, the improvement upon the standard-of-care; the process and timing of anticipated future development of Vaxcyte’s vaccine candidates; the timing and availability of data for the VAX-24 Phase 2 and Phase 3 studies and related regulatory interactions; the timing and submission of an IND application for the VAX-24 Phase 2 infant study and the availability of Phase 2 topline results; the timing and submission of an IND application for the VAX-XP adult program and the timing and availability of the Phase 1/2 topline data for such program; the demand for Vaxcyte’s vaccine candidates; and other statements that are not historical fact. The words “anticipate,” “believe,” “could,” “expect,” “intend,” “potential,” “should,” “would” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) convey uncertainty of future events or outcomes and 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, and the risks and uncertainties inherent with preclinical and clinical development processes; the success, cost and timing of all development activities and clinical trials; impacts of COVID-19; 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, without limitation, its Quarterly Report on Form 10-Q filed with the SEC on August 8, 2022 or in other documents Vaxcyte subsequently files with or furnishes to the SEC. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on management’s assumptions and estimates as of such date, and readers should not rely upon the information in this press release as current or accurate after its publication date. 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

⁽¹⁾ Lower bound of the 2-sided 95% confidence interval of the OPA geometric mean titer ratio is greater than 0.5.

⁽²⁾ Lower bound of the 2-sided 95% confidence interval of the difference in the proportions of participants with a ≥4-fold increase from Day 1 to Day 29 is greater than 10%, and lower bound of the 2-sided 95% confidence interval of the OPA geometric mean titer ratio is greater than 2.0.

Contacts:

Andrew Guggenhime, President and Chief Financial Officer

Vaxcyte, Inc.

650-837-0111

investors@vaxcyte.com

Janet Graesser, Vice President, Corporate Communications and Investor Relations

Vaxcyte, Inc.

917-685-8799

media@vaxcyte.com

EX-99.2

VAX-24 Phase 1/2 Proof-of-Concept Study Topline Results October 24, 2022 Exhibit 99.2

October 2022 Forward-Looking Statements This presentation contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements related to the potential benefits of Vaxcyte’s vaccine candidates, including breadth of coverage and the ability to deliver a potentially best-in-class pneumococcal conjugate vaccine; demand for Vaxcyte’s vaccine candidates; the process and timing of anticipated future development and manufacture of Vaxcyte’s vaccine candidates; the achievement of future funding milestones; the growth and expansion of the pneumococcal vaccine market; the market opportunity for Vaxcyte’s vaccines; Vaxcyte’s expectations regarding the spectrum coverage, regulatory pathway, adoption speed and immunogenicity of its vaccine candidates; the timing of the initiation, progress and expected results of Vaxcyte’s preclinical studies, clinical trials and research and development plans (including, the availability of data for the VAX-24 Phase 2 and Phase 3 studies and related regulatory interactions; the submission of a VAX-24 infant IND application and initiation of such study; and the design of the VAX-XP clinical program, the submission of such IND and the availability of topline data); 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; 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 August 8, 2022 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.

Unprecedented Results Support Best-in-Class Potential for VAX-24 and Identify Optimal Dose for Advancement Summary of VAX-24 Phase 1/2 Topline Data Findings October 2022 SAFETY: VAX-24 demonstrated a safety and tolerability profile similar to Prevnar 20™ (PCV20) for all doses IMMUNOGENICITY: Met or exceeded regulatory standard for all 24 serotypes (STs) for VAX-24 conventional 2.2mcg dose without the need to push dose higher Optimal 2.2mcg dose being advanced to Phase 3: Met the standard OPA response non-inferiority criteria for all 20 STs common with PCV20, of which 16 achieved higher immune responses Met the standard superiority criteria for all 4 additional STs unique to VAX-24 All VAX-24 doses (1.1mcg, 2.2mcg, and 2.2mcg/4.4mcg) eligible to advance MILESTONES: Vaxcyte to pursue Breakthrough Therapy Designation to rapidly advance VAX-24 program Adults: Topline data from Phase 2 study in adults 65+ expected in 1H:23, followed by end-of-Phase 2 meeting with FDA to gain agreement on Phase 3 pivotal non-inferiority study using similar design as Phase 2 POC study Pediatrics: Infant IND submission and Phase 2 study initiation expected in 1H:23 PLATFORM: VAX-24 data validate Vaxcyte’s carrier-sparing PCV franchise to increase spectrum of coverage AND maintain robust immune responses to serotypes in current standard-of-care PCVs

October 2022 Streptococcus pneumoniae is the most common pathogen causing pneumococcal disease (PD). In the U.S. alone, there are ~900K pneumococcal pneumonia cases per year resulting in ~150K hospitalizations. Among children < age 5, PD is a leading cause of death globally. Circulating strains of PD in the U.S. and globally are associated with high case-fatality rates, antibiotic resistance and/or meningitis. Global Impact of Pneumococcal Disease Remains Significant Circulating Disease Driven by Serotypes Outside of Current PCVs 1 Gierke 2015 2 https://www.cdc.gov/abcs/reports-findings/survreports/spneu18.pdf CDC 2018 3 https://www.cdc.gov/pneumococcal/clinicians/clinical-features.html

5 October 2022 Significant Unmet Needs Remain Despite Available Vaccines Spectrum of Coverage Drives Adoption in PCV Segment Data in the US is for 2017, inclusive of those > 5 yrs of age. Varghese et al. Clin Micro and Infect (2020) 26(4): 512.e1-512.e10. PCV20 PCV15 PCV13 Designed to provide broadest coverage of any PCV, including an incremental 10-15% coverage of IPD in adults VAX-24 provides the benefits of a conjugate vaccine while fully eclipsing the coverage of Pneumovax 23 VAX-24 PROFILE

October 2022 Site-Specific Conjugation Using Cell-Free Platform to Go Beyond Limits of Conventional Chemistry Carrier-Sparing Approach for PCV Franchise Validated By POC Study Random conjugation masks “on-target” T-cell epitopes on the protein carrier Higher ratio of protein carrier to polysaccharide required Overabundance of protein carrier and its “off-target” effects exacerbates competition for CD4+ T-cell leading to carrier suppression LIMITATIONS OF CONVENTIONAL conjugation CHEMISTRY Site-specifically attach conventional antigens and protein carriers to: Enable consistent exposure of T-cell epitopes (and/or B-cell epitopes) on protein carrier to drive class-defining CD4+ help Avoid “off-target” effects from protein carrier that compete for the CD4+ help Enable use of less protein carrier per conjugate without sacrificing immunogenicity Enable broader-spectrum carrier-sparing conjugate vaccines VAXCYTE’s SUPERIOR carrier-sparing CONJUGATE VACCINES

October 2022 ~$13B ~$7B Market Growth Prevnar 13 Pneumovax 23 Synflorix Billions Other Sources: Company websites; Prevnar 20 and Vaxneuvance have since been approved in 2021. Global Pneumococcal Vaccine Market (2022-2027), Infogence Global Research. Shea KM, Edelsberg J, Weycker D et al. (2014), Open Forum Infect Dis 1(1): ofu024. ACIP recently voted to support PCV20 “catch-up” for adults who previously received PCV13 and Pneumovax 23 “At risk” adults recently added to U.S. universal PCV vaccination recommendation, which includes >25% of 50-64 year olds 1 PCV Market Growth Drivers Strong ACIP consideration to expand U.S. universal adult vaccination to >50 years from >65 would significantly expand market Would necessitate prime-boost for effective long-term protection, which has been limited by continued availability of Pneumovax 23 Premium price for PCV20 and PCV15 shows value of additional serotype coverage 2027E 2 Global Pneumococcal Vaccine Market PCV Market Growth Expected to Reach ~$13B by 2027 Driven Primarily by Growth in Adult Market Pneumococcal Vaccine Market Poised for Significant Growth

VAX-24 Phase 1/2 Study Design October 2022

October 2022 VAX-24 Phase 1/2 Clinical Proof-of-Concept Study Design Design: Randomized, Observer-Blind, Dose-Finding, Controlled Study to Evaluate Safety, Tolerability & Immunogenicity of VAX-24 vs SOC in Adults Aged 18-64 Safety Follow-Up Pilot Phase 1 Safety Healthy Adults 18 to 49 (n=64) Immunogenicity Assessment Day 29 Day 0 Month 6 Dose Blood Sample Clinical POC Phase 2 Study Healthy Adults 50 to 64 (n=771) Day 0 Month 6 Day 8 Final Safety Assessment Screen Randomize (1:1:1:1) VAX-24 Low Dose 1.1mcg VAX-24 Middle Dose 2.2mcg VAX-24 Mixed Dose 2.2mcg/4.4mcg* PCV20 Day 29 Dose DMC Review Screen Randomize (1:1:1:1) PCV20 VAX-24 Low Dose 1.1mcg VAX-24 Middle Dose 2.2mcg VAX-24 Mixed Dose 2.2mcg/4.4mcg* IgG & OPA VAX-24 vs PCV20 (common 20 strains) Final Safety Assessment Safety Follow-Up * For the VAX-24 Mixed Dose, a 4.4mcg dose is used for serotypes 3, 6B, 7F, 9V, 18C, 19A and 19F; a 2.2 mcg dose is used for the remaining serotypes. .

Study Evaluated Three VAX-24 Doses October 2022 1 3 4 5 6A 6B 7F 8 9V 10A 11A 12F 14 15B 18C 19A 19F 22F 23F 33F 2 9N 17F 20 4.4 mcg 4.4 mcg 4.4 mcg 4.4 mcg 4.4 mcg 4.4 mcg 4.4 mcg 4.4 mcg Low Dose (1.1mcg) Middle Dose (2.2mcg) Mixed Dose (2.2mcg/ 4.4mcg) PCV20 VAX-24 (2.2mcg) Mixed Dose includes seven serotypes at 4.4mcg strategically chosen based on epidemiological relevance or prior evidence of dose-dependent immune responses to increase the probability of generating non-inferior immune responses for those serotypes.

Study Safety, Tolerability and Immunogenicity Outcome Measures October 2022 Safety and Tolerability Outcome Measures  (Phase 1 and 2 portions of the study) Immunogenicity Outcome Measures (Phase 2 portion of the study ONLY) DAY 7 DAY 29 DAY 180 Solicited local reactions Solicited systemic events Unsolicited adverse events (AEs) Serious adverse events (SAEs) SAEs and new onset of chronic illnesses (NOCI) medically attended adverse events Opsonophagocytic assay (OPA) geometric mean titer (GMTs) IgG geometric mean concentration (GMCs) % of subjects achieving a 4-fold rise in OPA Geometric Mean Ratios (GMR) in serotype-specific OPA

VAX-24 Phase 1/2 Study Disposition and Demographics October 2022

Overall High Proportion of Subjects with Safety and Immunogenicity Follow-Up Phase 1/2 Study Disposition October 2022 Phase 1 Safety Healthy Adults 18 to 49 (n=64) Phase 2 POC Study Healthy Adults 50 to 64 (n=771) 9 subjects were lost to follow-up in Phase 2 Enrolled N = 64 Included in Safety Population N = 16 (100.0%) Included in Safety Population N = 16 (100.0%) Included in Safety Population N = 16 (100.0%) Included in Safety Population N = 16 (100.0%) Vaccinated PCV20 N = 16 Vaccinated VAX-24 Low Dose N = 16 Vaccinated VAX-24 Middle Dose N = 16 Vaccinated VAX-24 Mixed Dose N = 16 Enrolled N = 771 Included in Safety Population N = 196 (100.00%) Included in Safety Population N = 191 (100.0%) Included in Safety Population N = 191 (100.0%) Included in Safety Population N = 193 (100.0%) Vaccinated PCV20 N = 196 Vaccinated VAX-24 Low Dose N = 193 Vaccinated VAX-24 Middle Dose N = 191 Vaccinated VAX-24 Mixed Dose N = 191 Included in Immunogenicity Population N = 166 (86.0%) Included in Immunogenicity Population N = 181 (94.3%) Included in Immunogenicity Population N = 172 (89.6%) Included in Immunogenicity Population N = 179 (92.3%) Ongoing N = 2 Discontinued N = 3 (4.7%) Completed N = 59 (92.2%)

Generally Balanced Across Cohorts and Similar for the Safety and Immunogenicity Populations Phase 2 Demographic Population October 2022 VAX-24 – Low Dose (1.1mcg) VAX-24 – Middle Dose (2.2mcg) VAX-24 – Mixed Dose (2.2mcg/4.4mcg) PCV20 Safety Immunogenicity Safety Immunogenicity Safety Immunogenicity Safety Immunogenicity Number of Subjects 193 166 191 181 191 172 196 179 Median age, years (range) 57.0 (50-64) 57.0 (50-64) 57.0 (50-64) 57.0 (50-64) 57.0 (50-64) 57.0 (50-64) 57.0 (50-64) 57.0 (50-64) Sex, n (%) Female 110 (57.0) 96 (57.8) 119 (62.3) 113 (62.4) 134 (70.2) 125 (72.7) 129 (65.8) 118 (65.9) Male 83 (43.0) 70 (42.2) 72 (37.7) 68 (37.6) 57 (29.8) 47 (27.3) 67 (34.2) 61 (34.1) Race, n (%) White 145 (75.1) 127 (76.5) 157 (82.2) 149 (82.3) 155 (81.2) 140 (81.4) 155 (79.1) 139 (77.7) Black 40 (20.7) 32 (19.3) 31 (16.2) 29 (16.0) 29 (15.2) 27 (15.7) 30 (15.3) 29 (16.2) Asian 1 (0.5) 1 (0.6) 0 (0.0) 0 (0.0) 2 (1.0) 2 (1.2) 3 (1.5) 3 (1.7) Native Hawaiian blinded blinded blinded blinded blinded blinded blinded blinded American Indian or Native Alaskan blinded blinded blinded blinded blinded blinded blinded blinded Other 3 (1.6) 2 (1.2) 2 (1.0) 2 (1.1) 1 (0.5) 1 (0.6) 2 (1.0) 2 (1.1) Median Height, cm (range) 168.3 (150-200) 168.4 (150-200) 167.6 (145-193) 167.6 (145-193) 167.6 (145-193) 167.6 (145-193) 167.6 (142-196) 167.6 (142-196) Median weight, kg (range) 87.82 (49.2-159.2) 86.87 (49.8-159.2) 86.80 (51.4-155.1) 86.80 (51.4-155.1) 83.01 (47.9-205.5) 83.10 (48.9-205.5) 82.83 (45.3-189.9) 82.70 (45.3-185.5) Median BMI, kg/m2 (range) 29.87 (18.0-55.0) 29.39 (18.8-55.0) 30.54 (18.7-52.6) 30.44 (18.7-52.6) 29.42 (18.0-57.3) 29.48 (18.0-57.3) 29.06 (17.4-72.7) 29.11 (17.4-72.7)

VAX-24 Phase 2 Study Topline Safety and Tolerability Results October 2022

Local Solicited AEs Similar to PCV20 and Across Cohorts Through Day 7 October 2022 Represents data for the 50 – 64 year age group; as of August 31, 2022.

Systemic Solicited AEs Similar to PCV20 and Across Cohorts Through Day 7 October 2022 Represents data for the 50 – 64 year age group; as of August 31, 2022.

VAX-24 Safety Profile Similar to PCV20 and Across Cohorts October 2022 VAX-24 – Low Dose (1.1mcg) VAX-24 – Middle Dose (2.2mcg) VAX-24 – Mixed Dose (2.2mcg/4.4mcg) PCV20 Number of Subjects 193 191 191 196 Subjects with TEAE, n (%) 29 (15.0) 21 (11.0) 22 (11.5) 31 (15.8) Subjects with SAE or NOCI, n (%) 2 (1.0) 3 (1.6) 5 (2.6) 4 (2.0) Subjects with related SAE, n (%)  0 0 0 0 Subjects with related NOCI, n (%)  0 0 0 0 Deaths, n (%) 0 0 0 0 Represents data for the 50 – 64 year age group; as of August 31, 2022.

VAX-24 Phase 2 Study Topline Immunogenicity Results October 2022

Criteria for 4 Incremental Serotypes in VAX-24:   Superiority Standard: Lower bound of the 2-sided 95% CI of the difference in the proportions of participants with a ≥4-fold increase from Day 1 to Day 29 is greater than 10% Lower bound of the 2-sided 95% CI of the OPA GMT ratio is greater than 2.0     Criteria for 20 Serotypes Common to VAX-24 and PCV20:   Non-inferiority Standard: Lower bound of the 2-sided 95% CI of the OPA GMT ratio is greater than 0.5 Superiority Standard: Lower bound of 2-sided 95% CI of the OPA GMT ratio is greater than 1.2 Lower bound of the 2-sided 95% CI of the difference in proportions of participants with a ≥4-fold increase from Day 1 to Day 29 is greater than 0 Standard Regulatory Criteria for Evaluating PCV Immunogenicity Results October 2022

VAX-24 2.2mcg Dose Met Regulatory Criteria for All 24 Serotypes October 2022 Met non-inferiority standard for all 20 common serotypes for the OPA GMR of VAX-24 : PCV20 Met superiority standard for all 4 incremental serotypes in VAX-24 based on 4-fold rise Non-inferiority Criteria (LL 95% CI ≥ 0.5 of GMR Ratio) Regulatory Threshold for Superiority (LL95%CI > 10%) * * * * * Reached statistical significance

2.2mcg Dose Demonstrated Higher OPA GMRs for 16 of the 20 Shared Serotypes and Will be Advanced All 3 Doses Induced Immune Responses Sufficient to Move to Phase 3 October 2022 X = 7 VAX-24 serotypes at the 4.4mcg dose; GMR = Geometric Mean Titers; LL= Lower Limit; CI = Confidence Interval

October 2022 Strong Evidence of a Dose-Dependent Response for the 7 VAX-24 Serotypes Tested at 1.1mcg, 2.2mcg and 4.4mcg 4.4mcg dose deemed not necessary as 2.2mcg dose demonstrated higher OPA GMRs for all 7 serotypes tested versus PCV20.

All 24 Serotypes in VAX-24 Demonstrated Robust OPA Immune Responses Serotypes Contained in PCV20 October 2022 OPA GMTs by Serotype Non-PCV20 Serotypes

All 24 Serotypes in VAX-24 Demonstrated Robust IgG Responses Non-PCV20 Serotypes Serotypes Contained in PCV20 October 2022 IgG GMCs by Serotype 0.1 1 10 IgG GMCs mcg/mLs (95% CI) GMC = Geometric Mean Concentration

Study Conclusions & Program Status October 2022

Supports Best-in-Class Potential for VAX-24 and Carrier-Sparing PCV Franchise Study Conclusions October 2022 VAX-24 demonstrated a safety and tolerability profile similar to PCV20 at all doses among 50-64 year olds Met or exceeded regulatory standard for all 24 serotypes (STs) for VAX-24 conventional 2.2mcg dose without the need to push dose higher Optimal 2.2mcg dose being advanced to Phase 3: Met the standard OPA response non-inferiority criteria for all 20 STs common with PCV20, of which 16 achieved higher immune responses Met the standard superiority criteria for all 4 additional STs unique to VAX-24 Learnings inform optimal design for VAX-XP clinical program given ability to add STs without sacrificing overall immune responses

October 2022 Well-Trodden Clinical Plan Aligned with Current FDA, EMA and WHO Guidance and Precedent PCVs Vaxcyte PCV Franchise Leverages Established Regulatory Pathway For adults: Lower limit of the 95% CI for the OPA GMR ≥0.5 for each serotype comparison. For infants: Lower limit of the 95% CI for the IgG GMC ratio post dose 4 is ≥0.5 and LL of the 95% CI for % of subjects achieving an IgG concentration ≥ 0.35 µg/mL 1 month after dose 3 is < -10%. 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/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM206140.pdf. Accessed January 10, 2020. 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. Licensure via non-inferior immune responses vs. SOC (1) Consistent with Merck (PCV15) & Pfizer (PCV20) BLAs(2)(3) Well-defined established surrogate immune endpoints No anticipated requirement for field efficacy trials Consistency across Ph 2 POC and Ph 3 pivotal studies for immune response in adult and infant programs (4)(5)(6) Current FDA, EMA & WHO Guidance and Precedent

Adult Program Topline safety, tolerability and immunogenicity data from Phase 2 study in adults 65 and older anticipated in 1H:23 Final results with 6-month safety data for both Phase 2 adult studies anticipated in 1H:23 Regulatory interactions to inform Phase 3 program anticipated in 2H:23 Topline data from Phase 3 non-inferiority study in adults expected in 2025 Pediatric Program Infant IND submission and Phase 2 study initiation anticipated in 1H:23 Topline data from infant primary 3-dose immunization series expected by 2025 VAX-24 Program Anticipated Key Milestones October 2022

Platform and Pipeline Update October 2022

Data in the US is for 2017, inclusive of those > 5 yrs of age. Varghese et al. Clin Micro and Infect (2020) 26(4): 512.e1-512.e10. PCV20 PCV15 PCV13 Vaxcyte Carrier-Sparing PCV Franchise Positioned to Deliver Broadest Coverage October 2022 Designed to provide coverage for ~95% of the pneumococcal disease currently circulating in the U.S. adult population Anticipate adult IND application submission to FDA in 2H:23 Topline data in adults expected in 2024 VAX-XP PROFILE AND ANTICIPATED MILESTONES

Vaxcyte PCV Franchise has Potential for Sustained Leadership in Growing >$7B Pneumococcal Vaccine Market 4 6B 9V 14 18C 19F 23F 1 5 7F 3 6A 19A 33F 22F 8 10A 11A 12F 15B 2 9N 17F 20 15A 16F 23A 23B 7C 31 35B Source: Prescribing information for Prevnar, Prevnar 13, Prevnar20, Synflorix, Vaxneuvance, and Prevnar 20. Company filings for Vaxcyte VAX-XP (31-Valent) VAX-24: Potential for category-leading 24-valent PCV incorporating carrier-sparing conjugates VAX-XP: Next-generation 31-valent PCV showcases franchise approach and scalability of carrier-sparing conjugates October 2022 VAX-24

October 2022 VAXCYTE MISSION STATEMENT We are on a global mission to engineer high-fidelity vaccines that protect humankind from the consequences of bacterial diseases.

October 2022 Q&A with Management Grant Pickering Chief Executive Officer, Director and Founder Jim Wassil Executive Vice President and Chief Operating Officer Andrew Guggenhime President and Chief Financial Officer

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Document and Entity Information	Oct. 24, 2022
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Entity Central Index Key	0001649094
Document Type	8-K
Document Period End Date	Oct. 24, 2022
Entity Registrant Name	Vaxcyte, Inc.
Entity Incorporation State Country Code	DE
Entity File Number	01-39323
Entity Tax Identification Number	46-4233385
Entity Address, Address Line One	825 Industrial Road
Entity Address, Address Line Two	Suite 300
Entity Address, City or Town	San Carlos
Entity Address, State or Province	CA
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City Area Code	650
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Security 12b Title	Common Stock, $0.001 par value per share
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