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CURRENT REPORT
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| Item 8.01 | Other Events. |
On April 17, 2023, Vaxcyte, Inc. (“Vaxcyte”) issued a press release announcing positive data from its Phase 2 study of its 24-valent pneumococcal conjugate vaccine candidate, VAX-24, in adults aged 65 and older and full six-month safety and tolerability data from its adult Phase 1/2 and Phase 2 studies. 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 April 17, 2023, Vaxcyte also made available the slide presentation attached as Exhibit 99.2 to this Current Report on Form 8-K, which is incorporated herein by reference.
| Item 9.01 | Financial Statements and Exhibits. |
(d) Exhibits
| Exhibit Number |
Description | |
| 99.1 | Press Release, dated April 17, 2023. | |
| 99.2 | Slide presentation, dated April 17, 2023. | |
| 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.
| VAXCYTE, INC. | ||||||||
| Date: April 17, 2023 | By: | /s/ Andrew Guggenhime | ||||||
| Andrew Guggenhime President and Chief Financial Officer | ||||||||
Exhibit 99.1
Vaxcyte Reports Positive Data from Phase 2 Study of its 24-Valent Pneumococcal Conjugate Vaccine Candidate, VAX-24, in Adults Aged 65 and Older and Full Six-Month Safety Data from Adult Phase 1/2 and Phase 2 Studies
— VAX-24 Showed Robust Immune Responses Across all 24 Serotypes (ST) at All Doses, Confirming Prior Phase 2 Results in Adults Aged 50-64 —
— VAX-24 2.2mcg Dose Met Opsonophagocytic Activity (OPA) Response Non-Inferiority Criteria for 18 of 20 STs Common with Prevnar 20® (PCV20) and Superiority Criteria for the Four Additional VAX-24 STs —
— VAX-24 2.2mcg Dose Showed Further Improvement in Overall Immune Responses vs. PCV20 Relative to Results from Phase 2 Study in Adults Aged 50-64 —
— Full Six-Month Safety Data from Both Adult Studies Demonstrated VAX-24 Safety and Tolerability Results Similar to PCV20 at All Doses Studied —
— Prespecified Pooled Immunogenicity Analyses of Data from Both Adult Phase 2 Studies Showed the VAX-24 2.2mcg Dose Met OPA Non-Inferiority Criteria for All 20 STs Common with PCV20 and Superiority Criteria for the Four Additional VAX-24 STs —
— VAX-24 Well-Positioned for Adult Phase 3 Program with Topline Data Anticipated in 2025 —
— Company to Host Webcast/Conference Call Today at 7:30 a.m. ET / 4:30 a.m. PT —
SAN CARLOS, Calif., April 17, 2023 — 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 results from the VAX-24 Phase 2 study in adults aged 65 and older, as well as data from the full six-month safety assessment and prespecified pooled immunogenicity analyses from both the Phase 2 study in adults aged 65 and older and the prior Phase 1/2 study in adults aged 18-64 (Phase 1 portion adults aged 18-49, Phase 2 portion adults aged 50-64). VAX-24, the Company’s lead, broad-spectrum 24-valent pneumococcal conjugate vaccine (PCV) candidate, is being studied for the prevention of invasive pneumococcal disease (IPD).
In the Phase 2 study in adults aged 65 and older, VAX-24 demonstrated robust OPA immune responses for all 24 serotypes at all doses studied, confirming the prior adult study results. The VAX-24 2.2mcg dose, which Vaxcyte plans to advance to Phase 3, showed an overall improvement in immune responses vs. PCV20 relative to the results from the prior Phase 2 study in adults aged 50-64. The six-month safety data from both studies showed safety and tolerability results for VAX-24 similar to PCV20 at all doses studied.
“We believe the positive results from the Phase 2 study in adults aged 65 and older confirm the clinical potential of VAX-24 in the adult population. Based on the overall strength of our data and the well-established regulatory pathway, we look forward to meeting with regulators and advancing VAX-24 into a pivotal Phase 3 study for which we expect topline data in 2025,” said Grant Pickering, Chief Executive Officer and Co-Founder of Vaxcyte. “We developed VAX-24 with the goal of creating a best-in-class PCV that provides broader coverage and better immune responses compared to the standard-of-care vaccines. These data support that objective and also demonstrate the potential of our PCV franchise, including VAX-31, our 31-valent PCV candidate.”
“The data from both studies demonstrate VAX-24 safety and tolerability results similar to PCV20 and across cohorts, including older adults evaluated in this most recent study who are at increased risk for complications from IPD,” said Jim Wassil, Executive Vice President and Chief Operating Officer of Vaxcyte. “The immunogenicity results from our Phase 2 studies reinforce the potential utility of our carrier-sparing approach and give us confidence in the potential for VAX-24 to provide an additional 10-28 percent of coverage of IPD in adults compared to the standard-of-care PCVs.”
Immunogenicity Results from Phase 2 Study in Adults Aged 65 and Older (n=207)
| • | VAX-24 showed robust immune responses across all 24 STs at all three doses tested (1.1mcg, 2.2mcg, and 2.2mcg/4.4mcg), confirming the results from the prior Phase 2 study results in adults aged 50-64 (n=771). |
| • | The VAX-24 2.2mcg dose: |
| • | Achieved target responses, as measured by the geometric mean ratio (GMR) of OPA responses for VAX-24 vs. PCV20, for all 24 STs, supporting the potential of VAX-24 to expand coverage and improve immunogenicity over the standard-of-care. |
| • | Met the OPA response non-inferiority criteria(1) for 18 of 20 STs common with PCV20 and met the superiority criteria(2) for all four additional STs unique to VAX-24. The two STs that did not reach the OPA response criteria had GMRs of 0.86 (15B) and 0.71 (22F). |
| • | Showed higher GMRs for 16 of 20 STs common with PCV20 and an overall improvement in immune responses vs. PCV20 relative to the results from the Phase 2 study in adults aged 50-64. |
Full Six-Month Safety Data from Both Adult Studies
The Company also reported the full six-month safety results from the VAX-24 Phase 2 study in adults aged 65 and older and the VAX-24 Phase 1/2 study in adults aged 18-64.
| • | Through six months, VAX-24 demonstrated safety and tolerability results similar to PCV20 across all ages and doses studied. |
| • | Frequently reported local and systemic reactions were generally mild-to-moderate, resolving within several days of vaccination, with no meaningful difference observed across the cohorts. |
| • | No serious adverse events or new onset chronic illnesses were considered to be related to study vaccines. In a VAX-24 arm of the Phase 2 study in adults aged 65 and older, one participant with multiple pre-existing risk factors suffered a sudden cardiac death six months post-vaccination, which the Principal Investigator determined was not related to study vaccine due to the participant’s history of hypertensive cardiovascular disease. |
Prespecified Pooled Immunogenicity Analyses of Data from VAX-24 Adult Phase 2 Studies
The Company conducted prespecified pooled analyses of data from both adult Phase 2 studies to evaluate the immunogenicity of VAX-24 in participants aged 50 and older (n~225/group) and aged 60 and older (n~100/group), which are representative populations for the planned VAX-24 Phase 3 pivotal study.
At the VAX-24 2.2mcg dose:
| • | In both analyses, VAX-24 met the OPA response non-inferiority criteria for all 20 STs common with PCV20 and met the superiority criteria for the four additional STs unique to VAX-24. |
| • | In the pooled group with participants aged 50 and older, VAX-24 met the OPA response non-inferiority criteria for all 20 STs common with PCV20, of which 16 achieved higher immune responses and four reached statistical significance. |
| • | In the pooled group with participants aged 60 and older, VAX-24 met the OPA response non-inferiority criteria for all 20 STs common with PCV20, of which 17 achieved higher immune responses and three reached statistical significance. |
Anticipated Key Milestones
Vaxcyte is advancing the clinical development of its PCV programs with several anticipated key upcoming milestones, including:
| • | VAX-24 Adult Program: |
| • | Conduct End-of-Phase 2 meeting with the U.S. Food and Drug Administration (FDA) in the second half of 2023 to inform the conduct of the adult Phase 3 program. |
| • | Announce topline safety, tolerability and immunogenicity data from the Phase 3 pivotal non-inferiority study in adults in 2025. |
| • | VAX-24 Infant Program: |
| • | Announce topline safety, tolerability and immunogenicity data from the primary three-dose immunization series of the infant Phase 2 study by 2025. |
| • | VAX-31 Adult Program: |
| • | Submit adult Investigational New Drug (IND) application to FDA in the second half of 2023. |
| • | Announce topline safety, tolerability and immunogenicity data from Phase 1/2 study in adults in 2024. |
Conference Call and Webcast
Vaxcyte will hold a webcast and conference call today, April 17, 2023, at 7:30 a.m. ET / 4:30 a.m. PT to discuss these results. To participate in the conference call, please dial (800) 267-6316 (domestic) or (203) 518-9783 (international) and refer to conference ID PCVX0417. 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 the VAX-24 Adult Clinical Program
Phase 2 Clinical Study in Adults Aged 65 and Older (VAX-24 Study 102, NCT05297578):
This Phase 2 study was a randomized, observer-blind, dose-finding, controlled study designed to evaluate the safety, tolerability and immunogenicity of a single injection of VAX-24 at three dose levels (1.1mcg, 2.2mcg and 2.2mcg/4.4mcg) and compared to a single injection of PCV20 in 207 healthy adults aged 65 and older. The prespecified immunogenicity endpoints of the study included an assessment of the induction of antibody responses, using OPA and Immunoglobulin G (IgG), at one month post-vaccination, for each of the three VAX-24 doses and compared to PCV20 and, for the additional four serotypes contained in VAX-24 and Pneumovax® 23 (PPSV23), but not in PCV20, the percentage of subjects that experienced a four-fold rise in antibody titers. Participants in the study were evaluated for safety through six months post-vaccination. The study enrolled subjects from 19 sites in the United States.
Phase 1/2 Clinical Proof-of-Concept Study in Adults 18-64 Years of Age (VAX-24 Study 101, NCT05266456):
The VAX-24 Phase 1/2 clinical proof-of-concept study was a randomized, observer-blind, dose-finding, controlled study designed to evaluate the safety, tolerability and immunogenicity of VAX-24 in healthy adults aged 18-64. 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 aged 18-49. 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 aged 50-64. The immunogenicity objectives of the Phase 2 portion of the study included an assessment of the induction of antibody responses, using OPA and IgG, at one month post-vaccination, for each of the three VAX-24 doses and compared to PCV20, and for the additional four serotypes contained in VAX-24 (and PPSV23), but not in PCV20, the percentage of subjects that experienced a four-fold rise in antibody titers. Participants in the study were evaluated for safety through six months post-vaccination. The study enrolled subjects from 13 sites in the United States.
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™ 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 January 2023, the FDA granted Breakthrough Therapy designation to VAX-24 for the prevention of IPD in adults. The Breakthrough Therapy designation process is designed to expedite the development and review of drugs that are intended to treat a serious or life-threatening condition.
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 320,000 people get pneumococcal pneumonia each year, which is estimated to result in approximately 150,000 hospitalizations and 5,000 deaths. Pneumococci also cause over 50% of all cases of bacterial meningitis in the United States. Antibiotics are used to treat PD, but some strains of the bacteria have developed resistance to treatments. The morbidity and mortality due to PD are 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, carrier-sparing PCV 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™ 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-31, a 31-valent PCV candidate; VAX-A1, a prophylactic vaccine candidate designed to prevent Group A Strep infections; VAX-PG, a therapeutic vaccine candidate designed to slow or stop the progression of periodontal disease; and VAX-GI, a vaccine program designed to prevent Shigella. 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 ability to deliver a potentially best-in-class PCV and the improvement upon the standard-of-care; the process and timing of anticipated future development of Vaxcyte’s 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 submission of the IND application for VAX-31 and regulatory interactions and the availability of data for the VAX-24 adult, VAX-24 infant and VAX-31 studies); the demand for Vaxcyte’s vaccine candidates; the potential benefits and opportunities available as a result of the Breakthrough Therapy designation for VAX-24 in adults; 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; 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 Annual Report on Form 10-K filed with the SEC on February 27, 2023 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. Readers should not rely upon the information in this press release as current or accurate after its publication date.
| (1) | Lower bound of the 2-sided 95% confidence interval of the OPA geometric mean 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 ratio is greater than 2.0. |
Contacts:
Janet Graesser, Vice President, Corporate Communications and Investor Relations
Vaxcyte, Inc.
917-685-8799
Jennifer Zibuda, Senior Director, Investor Relations
Vaxcyte, Inc.
860-729-8902
VAX-24 Phase 2 Program Results, Including Adult 65+ Data and Full Six-Month Safety Data from Both Studies April 17, 2023 Exhibit 99.2
April 2023 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 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 submission of the IND application for VAX-31 and regulatory interactions and the availability of data for the VAX-24 adult, VAX-24 infant and VAX-31 studies); and other statements that are not historical fact. The words “anticipate,” “believe,” “continue,” “could,” “designed,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These forward-looking statements are based on Vaxcyte’s current expectations and actual results and timing of events could differ materially from those anticipated in such forward-looking statements as a result of risks and uncertainties, including, without limitation, risks related to Vaxcyte’s product development programs, including development timelines, success and timing of chemistry, manufacturing and controls and related manufacturing activities; potential delays or inability to obtain and maintain required regulatory approvals for its vaccine candidates; the risks and uncertainties inherent with preclinical and clinical development processes; the success, cost and timing of all development activities and clinical trials; and the sufficiency of cash and other funding to support Vaxcyte’s development programs and other operating expenses, any of which could materially and adversely affect Vaxcyte’s business and operations. These and other risks are described more fully in Vaxcyte’s filings with the Securities and Exchange Commission (SEC), including its Annual Report on Form 10-K filed with the SEC on February 27, 2023 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.
Introduction and vax-24 Results Overview VAX-24 Phase 2 Study results in Adults Aged 65 and Older (65+) Disposition and Demographics Safety and Tolerability Data Immunogenicity Data Prespecified Pooled Immunogenicity Analyses of both Phase 2 Adult Studies Full Six-Month Safety Data from both Adult Studies Program Conclusions, Status and Next Steps Agenda April 2023
Introduction and VAX-24 Results Overview April 2023
Summary: VAX-24 Adult 65+ Study Results Confirm Prior Phase 2 Results Positive Results Support Best-in-Class Potential for VAX-24 and Set Stage for Phase 3 Design and Advancement April 2023 SAFETY: Full six-month safety data from Phase 2 study in adults aged 65+ and prior Phase 1/2 study in adults aged 18-64 demonstrate VAX-24 safety and tolerability results similar to Prevnar 20® (PCV20) at all doses studied IMMUNOGENICITY: 65+ study achieved target responses for all 24 serotypes at 2.2mcg dose, demonstrating potential of VAX-24 to expand coverage and improve immunogenicity over standard-of-care Phase 2 65+ study results (n~45/arm): VAX-24 met OPA response non-inferiority criteria for 18/20 STs common with PCV20 and met the superiority criteria for all four additional STs unique to VAX-24 VAX-24 showed overall improvement in immune responses vs. PCV20 relative to results from Phase 2 in adults aged 50-64 and higher GMRs for 16/20 STs common with PCV20 ANTICIPATED PCV FRANCHISE MILESTONES: VAX-24 Adults: End-of-Phase 2 meeting with FDA 2H:23; Phase 3 pivotal immunogenicity data in 2025 VAX-24 Infants: Phase 2 study enrolling subjects, topline data from the primary three-dose immunization series by 2025 VAX-31 Adults: IND application submission 2H:23; topline data from Phase 1/2 study in 2024 PLATFORM: New data further support potential of our carrier-sparing PCV franchise and cell-free platform VAX-24 WELL-POSITIONED FOR ADULT PHASE 3 PIVOTAL PROGRAM 2.2mcg confirmed as optimal VAX-24 dose to advance to Phase 3 pivotal study, which will include adults 50+ or 60+ Prespecified pooled analyses of both Phase 2 adult studies for adults 50+ (n~225/group) and 60+ (n~100/group) met OPA response non-inferiority criteria for all 20 common STs and met superiority criteria for four additional STs unique to VAX-24 End-of-Phase 2 meeting with FDA to confirm study size and population (anticipate n~750/arm) OPA = Opsonophagocytic Activity; STs = serotypes; GMR = Geometric Mean Ratio
April 2023 Streptococcus pneumoniae is the most common pathogen causing pneumococcal disease (PD). In the U.S. alone, there are ~320K pneumococcal pneumonia cases per year resulting in ~150K hospitalizations. Invasive pneumococcal disease (IPD) is a leading cause of invasive disease in children two years of age and under. 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 Gierke 2015 https://www.cdc.gov/pneumococcal/clinicians/clinical-features.html
April 2023 Spectrum of Coverage Drives Adoption in PCV Segment Significant Unmet Needs Remain Despite Available Vaccines 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 currently approved PCV, including an incremental 10-28% coverage of IPD in U.S. adults vs. the SOC PCVs (PCV20/PCV15) today. Designed to provide the benefits of a conjugate vaccine while surpassing the coverage of Pneumovax 23. VAX-24 TARGET PRODUCT PROFILE 10% 28% PCV13 = Prevnar 13®, PCV15 = VAXNEUVANCE™
April 2023 Carrier-Sparing Approach for PCV Franchise Validated By Phase 2 Program Site-Specific Conjugation Using Cell-Free Platform to Go Beyond Limits of Conventional Chemistry 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 designed 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 UNIQUE carrier-sparing CONJUGATE VACCINES
April 2023 ~$13B ~$7B Market Growth Pfizer (Prevnar Family – PCV13 & PCV20) Merck (PPV23 & PCV15) GSK (Synflorix) Billions Other Sources: Company websites; includes Merck’s PCV15 sales disclosed for Q4 2022. 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 olds3 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 Pneumococcal Vaccine Market Poised for Significant Growth Expected to Reach ~$13B by 2027 Driven Primarily by Growth in Adult Market ACIP = Advisory Committee on Immunization Practices
VAX-24 Phase 2 Study in Adults 65+ April 2023
Study Design April 2023
Overview of VAX-24 Phase 2 Clinical Study in Adults 65+ April 2023 Design: Randomized, Observer-Blind, Dose-Finding, Controlled Clinical Study to Evaluate Safety, Tolerability & Immunogenicity of VAX-24 vs. Standard-of-Care (PCV20) in Healthy Adults Aged 65 and Older Day 1 Dose Blood Sample Phase 2 Study Adults Aged 65 and Older (n=207) Prevnar 20 (PCV20) VAX-24 Low Dose 1.1mcg VAX-24 Middle Dose 2.2mcg VAX-24 Mixed Dose 2.2mcg/4.4mcg* OPA & IgG VAX-24 vs PCV20 Final Safety Assessment Safety Follow-Up Day 29 Month 6 Immunogenicity Assessment Randomize (1:1:1:1) Screen * For the VAX-24 Mixed Dose, a 4.4mcg dose is used for serotypes 3, 6B, 7F, 9V, 18C, 19A and 19F; a 2.2mcg dose is used for the remaining serotypes. .
Study Evaluated Three VAX-24 Doses Consistent with Prior Phase 2 Study April 2023 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 Key Outcome Measures April 2023 Safety and Tolerability Outcome Measures Immunogenicity Outcome Measures DAY 7 DAY 29 DAY 180 Solicited local reactions Solicited systemic events Unsolicited adverse events (AE) Serious adverse events (SAE) SAE, new onset of chronic illnesses (NOCI) and medically attended adverse events (MAAE) Opsonophagocytic assay (OPA) geometric mean titer (GMT) IgG geometric mean concentration (GMC) % of subjects achieving a 4-fold rise in OPA Geometric Mean Ratios (GMR) in serotype-specific OPA
Disposition and Demographics April 2023
Study Disposition Overall High Proportion of Subjects with Safety and Immunogenicity Follow-Up April 2023 Phase 2 Study in Adults 65+ 7 Subjects (3.4%) Discontinued Enrolled N = 207 Included in Safety Population N = 50 (98.0%) Included in Safety Population N = 53 (100.0%) Included in Safety Population N = 51 (100.0%) Included in Safety Population N = 52 (100.0%) Vaccinated PCV20 N = 51 Vaccinated VAX-24 Low Dose (1.1mcg) N = 52 Vaccinated VAX-24 Middle Dose (2.2mcg) N = 51 Vaccinated VAX-24 Mixed Dose (2.2/4.4mcg) N = 53 Included in Immunogenicity Population N = 48 (92.3%) Included in Immunogenicity Population N = 47 (92.2%) Included in Immunogenicity Population N = 48 (90.6%) Included in Immunogenicity Population N = 45 (88.2%)
Demographic Population Generally Balanced Across Cohorts and Similar for the Safety and Immunogenicity Populations April 2023 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 52 48 51 47 53 48 50 45 Median Age, Years (range) 67.5 (65-80) 67.5 (65-80) 66.0 (65-79) 66.0 (65-79) 67.0 (65-88) 67.0 (65-88) 67.0 (65-80) 67.0 (65-80) Sex, n (%) Female 38 (73.1) 35 (72.9) 34 (66.7) 32 (68.1) 37 (69.8) 33 (68.8) 30 (60.0) 27 (60.0) Male 14 (26.9) 13 (27.1) 17 (33.3) 15 (31.9) 16 (30.2) 15 (31.3) 20 (40.0) 18 (40.0) Race, n (%) White 44 (84.6) 40 (83.3) 40 (78.4) 37 (78.7) 38 (71.7) 33 (68.8) 35 (70.0) 31 (68.9) Black 7 (13.5) 7 (14.6) 10 (19.6) 9 (19.1) 14 (26.4) 14 (29.2) 14 (28.0) 13 (28.9) Asian 0 (0) 0 (0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Native Hawaiian 0 (0) 0 (0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) American Indian or Native Alaskan 1 (1.9) 1 (2.1) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Other 0 (0) 0 (0) 1 (2.0) 1 (2.1) 1 (1.9) 1 (2.1) 0 (0.0) 0 (0.0) Multiracial 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (2.0) 1 (2.2) Median Height, cm (range) 165.5 (146-183) 165.5 (146-183) 166.6 (151-194) 166.6 (151-194) 167.6 (145-188) 167.6 (145-188) 166.5 (150-185) 166.6 (150-185) Median Weight, kg (range) 75.05 (50.6-161.9) 74.91 (50.6-161.9) 80.01 (48.5-150.0) 80.70 (48.5-150.0) 86.32 (53.5-130.2) 85.35 (53.5-130.2) 81.33 (47.7-147.4) 81.65 (47.7-147.4) Median BMI, kg/m2 (range) 27.42 (20.4-50.7) 27.36 (20.4-50.7) 28.92 (19.9-49.2) 29.04 (19.9-49.1) 29.64 (20.1-44.9) 28.99 (20.1-44.9) 29.38 (17.6-52.5) 29.77 (17.6-52.5)
Safety and Tolerability Data April 2023
Local Solicited AEs Similar to PCV20 and Across Cohorts Through Day 7 April 2023
Systemic Solicited AEs Similar to PCV20 and Across Cohorts Through Day 7 April 2023 .
Immunogenicity Data April 2023
Criteria for FOUR Incremental Serotypes in VAX-24: Superiority: 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 GMR is greater than 2.0 Criteria for 20 Serotypes Common to VAX-24 and PCV20: Non-inferiority: Lower bound of the 2-sided 95% CI of the OPA GMR is greater than 0.5 Superiority: Lower bound of 2-sided 95% CI of the OPA GMR 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 Precedent Regulatory Criteria for Phase 2/3 PCV Immunogenicity Studies April 2023 CI = confidence interval .
VAX-24 2.2mcg Dose Showed Robust Immune Responses for All 24 Serotypes April 2023 Met non-inferiority criteria for 18 of 20 common STs for the OPA GMR of VAX-24 : PCV20 (n~45) Met superiority criteria for all four incremental STs in VAX-24 based on 4-fold rise vs. PCV20 (n~45) Non-inferiority Criteria: LL 95% CI GMR ≥ 0.5 Threshold for Superiority (LL95%CI > 10%) * * Upper Limit = 4.93; sample size of 45 calculated as median between immunogenicity evaluable VAX-24 n=47 and PCV20 n=45 rounded to nearest 5. GMR:
65+ Study Results Confirm 2.2mcg is Optimal Dose to Advance to Phase 3 Consistent with Prior Phase 2 Study, 2.2mcg Dose Demonstrated Higher OPA GMR for 16/20 Shared STs April 2023 X = 7 VAX-24 serotypes at the 4.4mcg dose; GMR = Geometric Mean Ratio; GMFR = Geometric Mean Fold Ratio GMR: GMFR:
All 24 Serotypes in VAX-24 Demonstrated Robust OPA GMT Immune Responses Serotypes Contained in PCV20 April 2023 Non-PCV20 Serotypes OPA = Opsonophagocytic Activity; GMT = Geometric Mean Titer
All 24 Serotypes in VAX-24 Demonstrated Robust IgG GMC Responses Non-PCV20 Serotypes Serotypes Contained in PCV20 April 2023 0.1 1 10 IgG GMCs mcg/mLs (95% CI) IgG = Immunoglobulin G; GMC = Geometric Mean Concentration
Prespecified Pooled Immunogenicity Analyses of Both VAX-24 Phase 2 Adult Studies April 2023
ST GMR 95%CI 1 1.56 3.33 0.73 3 0.91 1.47 0.56 4 1.33 2.55 0.70 5 1.18 2.49 0.55 6A 1.96 4.93 0.78 6B 1.28 2.99 0.55 7F 0.90 1.60 0.51 8 1.32 2.34 0.74 9V 1.65 3.59 0.76 10A 1.17 2.39 0.58 11A 1.31 1.89 0.91 12F 1.6 3.77 0.68 14 1.31 2.42 0.70 15B 0.86 1.88 0.39 18C 1.69 3.20 0.89 19A 1.52 2.53 0.92 19F 1.53 2.69 0.87 22F 0.71 1.40 0.36 23F 1.31 3.24 0.53 33F 1.19 2.18 0.65 Phase 2 Program Confirms 2.2mcg as Optimal Dose in Adult Population 65+ Study Data Show Further Improvement in Overall Immune Response vs. PCV20 April 2023 * Upper Limit = 4.93; sample size of 180 calculated as median between immunogenicity evaluable VAX-24 n=179 and PCV20 n=181 rounded to nearest 10. * ST GMR 95%CI 1 0.89 1.23 0.64 3 1.19 1.51 0.93 4 1.21 1.55 0.95 5 0.79 1.13 0.55 6A 0.92 1.32 0.64 6B 1.23 1.68 0.89 7F 1.1 1.39 0.87 8 1.1 1.38 0.87 9V 1.75 2.42 1.26 10A 1.05 1.37 0.8 11A 1.04 1.13 0.95 12F 1.21 1.69 0.86 14 1.18 1.59 0.87 15B 1.03 1.42 0.75 18C 1.75 2.31 1.33 19A 1.17 1.51 0.92 19F 1.65 1.98 1.38 22F 0.94 1.25 0.71 23F 1.42 2.08 0.97 33F 1.55 1.99 1.21 GMR: GMFR: GMR: GMFR:
Met Standard OPA Response Non-Inferiority Criteria for All 20 Common STs Prespecified Pooled Analyses Support Advancement of VAX-24 to Phase 3 April 2023 Sample size of ~225 calculated as median between immunogenicity evaluable VAX-24 n=228 and PCV20 n=224 rounded to nearest 5 for 50+ and ~100 calculated as median between immunogenicity evaluable VAX-24 n=101 and PCV20 n=104 rounded to nearest 5 for 60+. GMR: GMFR: GMR: GMFR:
Full Six-Month Safety and Tolerability Data from Both VAX-24 Adult Studies April 2023
Six-Month Safety Data from VAX-24 Phase 2 Study in Adults Aged 65+ Safety Results Similar to PCV20 and Across Cohorts April 2023 VAX-24 – Low Dose (1.1mcg) VAX-24 – Middle Dose (2.2mcg) VAX-24 – Mixed Dose (2.2mcg/4.4mcg) PCV20 Number of Subjects with 52 51 53 50 Unsolicited TEAE, n (%) 6 (11.5) 4 (7.8) 4 (7.5) 8 (16.0) Related Unsolicited TEAE, n (%) 1 (1.9) 4 (7.8) 2 (3.7) 5 (10.0) MAAE, n (%) 5 (9.6) 3 (5.9) 3 (5.7) 6 (12.0) Related MAAE, n (%) 0 0 1 (1.9) 0 NOCI, n (%) 1 (1.9) 1 (2.0) 1 (1.9) 0 Related NOCI, n (%) 0 0 0 0 SAE, n (%) 1 (1.9) 1 (2.0) 1 (1.9) 0 Related SAE, n (%) 0 0 0 0 Death, n (%) 0 1 (2.0)1 0 0 Related Death, n (%) 0 0 0 0 66-year-old white, obese male (BMI:47.4) with hypertension. No solicited AEs were reported after vaccination. Participant suffered sudden cardiac death six months post-vaccination determined by Principal Investigator to be not related to study product due to participant’s history of hypertensive cardiovascular disease. TEAE = Treatment emergent adverse events Excludes Solicited AEs
Six-Month Safety Data from VAX-24 Phase 1/2 Study in Adults Aged 18-64 Safety Results Similar to PCV20 and Across Cohorts April 2023 VAX-24 – Low Dose (1.1mcg) VAX-24 – Middle Dose (2.2mcg) VAX-24 – Mixed Dose (2.2mcg/4.4mcg) PCV20 Number of Subjects with 209 207 207 212 Unsolicited TEAE, n (%) 32 (15.3) 24 (11.6) 26 (12.6) 34 (16.0) Related Unsolicited TEAE, n (%) 4 (1.9) 9 (4.3) 5 (2.4) 8 (3.8) MAAE, n (%) 27 (12.9) 26 (12.6) 24 (11.6) 31 (14.6) Related MAAE, n (%) 0 0 0 0 NOCI, n (%) 3 (1.4) 3 (1.4) 6 (2.9) 5 (2.4) Related NOCI, n (%) 0 0 0 0 SAE, n (%) 2 (1.0) 3 (1.4) 1 (0.5) 4 (1.9) 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 Excludes Solicited AEs
Combined Six-Month Safety Data from Both Adult VAX-24 Studies Safety Results Similar to PCV20 and Across Cohorts April 2023 VAX-24 – Low Dose (1.1mcg) VAX-24 – Middle Dose (2.2mcg) VAX-24 – Mixed Dose (2.2mcg/4.4mcg) PCV20 Number of Subjects with 261 258 260 262 Unsolicited TEAE, n (%) 38 (14.6) 28 (10.9) 30 (11.5) 42 (16.0) Related Unsolicited TEAE, n (%) 5 (1.9) 13 (5.0) 7 (2.7) 13 (5.0) MAAE, n (%) 32 (12.2) 29 (11.2) 27 (10.4) 37 (14.1) Related MAAE, n (%) 0 0 1 (0.4) 0 NOCI, n (%) 4 (1.5) 4 (1.6) 7 (2.7) 5 (1.9) Related NOCI, n (%) 0 0 0 0 SAE, n (%) 3 (1.1) 4 (1.6) 2 (0.77) 4 (1.5) Related SAE, n (%) 0 0 0 0 Death, n (%) 0 1 (0.39)1 0 0 Related Death, n (%) 0 0 0 0 66-year-old white, obese male (BMI:47.4) with hypertension. No solicited AEs were reported after vaccination. Participant suffered sudden cardiac death six months post-vaccination determined by Principal Investigator to be not related to study product due to participant’s history of hypertensive cardiovascular disease. TEAE = Treatment emergent adverse events Excludes Solicited AEs
Phase 2 Program Conclusions, Status & Next Steps April 2023
Full six-month VAX-24 data (n=779) showed safety and tolerability results similar to PCV20 Improved immunogenicity vs. PCV20 with no evidence of dose-dependent safety and tolerability issues Confirmed 2.2mcg as optimal dose to advance to Phase 3 pivotal study Achieved target immune responses for all 24 serotypes in both Phase 2 studies Met non-inferiority criteria for all 24 STs in prespecified pooled analyses, with sample sizes expected to increase in Phase 3 program (n~750/arm) Well-established regulatory pathway, with multiple precedents of approval based on surrogate immune endpoints Historically, consistent study design and endpoints across Phase 2 and pivotal Phase 3 programs Precedent Phase 3 programs and VAX-24 Phase 2 data support flexibility of choice in ultimate adult age range for pivotal study With positive Phase 2 data, Vaxcyte is excited to advance VAX-24 into Phase 3 Positive Phase 2 Program Results Support Best-in-Class Potential for VAX-24 and Set Stage for Phase 3 Program April 2023 SUCCESSFUL VAX-24 PHASE 2 PROGRAM MET ALL KEY OBJECTIVES WELL-POSITIONED FOR PHASE 3 PIVOTAL PROGRAM
Anticipated PCV Franchise Milestones for 2023-20251 Vaxcyte is Advancing Clinical Development of VAX-24 and VAX-31 with Several Key Upcoming Milestones April 2023 Conduct FDA End-of-Phase 2 meeting to finalize adult Phase 3 program in 2H:23 Announce topline safety, tolerability and immunogenicity data from the Phase 3 pivotal non-inferiority study in adults in 2025 Submit adult IND application to FDA in 2H:23 Announce topline safety, tolerability and immunogenicity data from adult Phase 1/2 study in 2024 VAX-24 Adult VAX-24 Infant VAX-31 Adult Announce topline safety, tolerability and immunogenicity data from the primary three-dose immunization series of the Phase 2 study by 2025 Guidance provided as of April 17, 2023.
April 2023 VAXCYTE MISSION STATEMENT We are on a global mission to engineer high-fidelity vaccines that protect humankind from the consequences of bacterial diseases.
April 2023 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
