Vaxcyte, Inc. Common Stock Study result

Please go ahead. Thank you, operator, and good morning, everyone.

Welcome to Vaxcyte's conference call to discuss top line results from OPUS-1, our pivotal Phase III trial evaluating VAX-31 in adults aged 18 and older. VAX-31 is our investigational 31-valent pneumococcal conjugate vaccine, or PCV, designed to prevent invasive pneumococcal disease, or IPD, and pneumococcal pneumonia. I am joined today by Grant Pickering, our Chief Executive Officer and co-founder, Jim Wassil, our Chief Scientific Officer and Chief Operating Officer, Luis Jodar, our Chief Medical Officer, and Mike Mullette, our Chief Commercial Officer. Earlier this morning, we issued a press release announcing these results. Copies of this and our other press releases, latest corporate presentation, and SEC filings can be found in the Investors and Media section of our website.

Before we begin, as noted on slide 3, I would like to remind you that during this call, we will be making certain forward-looking statements about Vaxcyte, which are subject to various risks, uncertainties, and other factors that could cause actual results to differ materially from those referred to in any forward-looking statements. For a discussion of the risks and uncertainties associated with these statements, please see our press release issued today as well as our most recent filings with the SEC, including the risk factors set forth in our Form 10-Q for the quarter ended June 30, 2026, and any subsequent reports filed with the SEC. With that, I will turn the call over to Grant.

Thank you, Andrew, and we appreciate you all joining us today. On behalf of the entire Vaxcyte team, I am immensely proud to share that OPUS-1 met all pre-specified primary immunogenicity endpoints across all ages studied. VAX-31 was also well-tolerated and demonstrated a safety profile similar to the licensed comparators in the study, Capvaxive or PCV21 and Prevnar 20 or PCV20. These results represent what we believe to be clear validation of VAX-31's potential to substantially broaden disease coverage while maintaining robust immune responses. They further support the potential of our site-specific carrier-sparing platform to deliver broader spectrum PCVs that address currently circulating disease-causing serotypes while maintaining pressure on historically prevalent serotypes. Today, we are presenting top-line results.

We will present the full data in a peer-reviewed scientific setting, and the complete OPUS-1 data set will serve as the cornerstone of our planned BLA alongside OPUS-2 and OPUS-3 results and a manufacturing consistency study. I will begin with the opportunity we see for VAX-31, the framework used to evaluate success in OPUS-1, and the top-line results. Jim Wassil will review disposition, demographics, tolerability, and safety, followed by Luis Jodar with the immunogenicity results. I will return with our next steps and closing remarks before we open the call to questions. Turning to slide 6, the pneumococcal vaccine class remains one of the largest and most durable segments of the vaccine market, with combined global sales of approximately $8.5 billion in 2025. Despite current vaccination efforts, the disease continues to be a major driver of global morbidity and mortality, and broader spectrum vaccines are needed.

While the infant segment currently represents the majority of revenues, the adult population is expected to be the primary driver of growth, with the combined market projected to reach $12 billion by 2030. To put the opportunity for VAX-31 in context, I would like to spend a few moments to orient you all as to how the category has evolved and the present trade-offs we have an opportunity to overcome with VAX-31 in order to prevent a substantial residual disease burden. Turning to slide 7, the success of pediatric PCVs reshaped pneumococcal disease 25 years ago. These vaccines protected children and reduced carriage and transmission, providing substantial indirect protection to adults. As vaccine-covered serotypes declined, other serotypes filled that void. This serotype replacement phenomenon drove the development of progressively broader vaccines, including PCV15 and PCV20, that retained the earlier serotypes while adding new ones.

Broader coverage has historically come with lower immune responses. This was evidenced with PCV20 compared with PCV13 in adults, where the responses for all but one of the overlapping 13 serotypes were numerically lower with PCV20, despite meeting non-inferiority for those shared serotypes. With substantial circulating disease over and above PCV20 coverage, the challenge has been to expand coverage while maintaining the magnitude of immune responses. PCV21 took a different approach to expand coverage, focusing specifically on the serotypes causing adult disease today. It added eight serotypes not included in PCV20 while leaving out nine of the historically important serotypes retained in PCV20. That approach increased the coverage of currently circulating adult disease but forced healthcare providers to make a choice between two vaccines, each of which has meaningful coverage gaps.

With the resurgence of serotype 4 from very low levels following pediatric vaccination, it is now one of the fastest-growing serotypes in western states and in Europe. Likewise, serotype 19F also continues to persist and requires continued inclusion to prevent further resurgence. Both are included in PCV20, but absent from PCV21. This has resulted in a difficult trade-off for healthcare providers as they choose between two equally recommended vaccines with partially overlapping coverage. At present, the market is split with a slight edge to PCV20. VAX-31 was designed to overcome these trade-offs by retaining all of the PCV20 serotypes, adding serotypes responsible for adult disease that are covered by PCV21, and expanding coverage even further. That required the incorporation of 31 serotypes into a single vaccine and demonstrating that immune responses can remain robust. Our site-specific conjugation and carrier-sparing technology is designed to rise to the challenge.

As you can see on this epidemiology slide seven, VAX-31 incorporates serotypes responsible for 95% of invasive pneumococcal disease and 88% of pneumococcal pneumonia in U.S. adults 50 and older, a greater proportion than either PCV20 or PCV21. The strength and consistency of our phase II data gave us confidence that we could broaden coverage without sacrificing immunogenicity. That gave us the conviction to take on the more stringent non-inferiority standard in our phase III study. With that backdrop, let's review the approval standard for immunogenicity and the pre-specified framework used to evaluate VAX-31 head-to-head with PCV20 and PCV21 in OPUS-1. Turning to slide eight, this slide puts the immune response standards in context. Opsonophagocytic activity, or OPA, is a functional measure of how well vaccine-induced antibodies help immune cells kill pneumococcus.

Because there is no established antibody threshold that reliably predicts protection in adults, we compare these responses with those of licensed vaccines. For each serotype, we measure the OPA geometric mean titer, or GMT, after VAX-31 and after the licensed comparator and calculate a ratio between the two, which is the geometric mean ratio or GMR. The dots in this slide illustrate the point estimates of the GMR, so VAX-31 divided by the comparator, and the horizontal lines show the two-sided 95% confidence intervals. The left end of each line is the lower bound of that confidence interval, which we'll use as shorthand LBCI going forward. The pivotal PCV20 and PCV21 trials required their lower bound to be greater than 0.5.

Given the concern that repeated bridging would lead to progressively lower immune responses, we aligned with the FDA to inaugurate a more stringent threshold of the LBCI greater than 0.667 in OPUS-1. In this slide, moving from left to right, the shaded blue area represents the historical threshold of 0.5. The gray area represents the higher OPUS-1 threshold of 0.667, approximately two-thirds of the comparator response rather than one-half. Farther to the right, the green area represents a lower bound greater than one, which indicates statistically greater immune responses. Finally, the purple area represents the primary superiority assessments involving the three unique serotypes and cross-reactive 20B, where the lower bound must exceed 2.0. We believe meeting the higher non-inferiority standard with a broader spectrum vaccine will set a new bar for future adult PCV development.

Turning to slide nine, let's review what VAX-31 needed to deliver to meet the study's primary endpoints. OPUS-1 was a complex study with two comparators, partially overlapping serotype coverage, and two different age groups. So let's break it down. It begins with the four co-primary immunogenicity endpoint groups in adults 50 and older. The first group contains the 11 serotypes shared by all three vaccines, where VAX-31 was compared with both PCV20 and PCV21. For each serotype, the primary criterion required non-inferiority to one or both comparators via the OPA GMRs, requiring the lower bound to exceed 0.667, inclusive of a pre-specified alpha penalty on a serotype by serotype basis in the protocol to account for the two comparisons.

For the second group, the nine serotypes unique to VAX-31 and PCV20 were compared to establish the OPA GMRs with the primary criterion for non-inferiority requiring the lower bound to exceed 0.667. For the third group, the eight serotypes unique to VAX-31 and PCV21 were compared using the same non-inferiority criterion. Together, these three groups account for all 28 shared serotypes evaluated for non-inferiority. The fourth group assessed superiority for the three serotypes unique to VAX-31, along with cross-reactive serotype 20B. These assessments used a superiority margin of 2.0 for the OPA geometric mean ratio, with success required against one or both comparators inclusive of a serotype by serotype pre-specified alpha penalty in the protocol to account for the two comparisons. Overall co-primary success in the trial required all of these 32 assessments to succeed, all 28 non-inferiority assessments, and all four superiority assessments.