Vaxcyte, Inc. 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.

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.

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. 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. 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 study enrolled subjects from 13 sites in the United States.

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.