While AMR is a complex crisis that no single solution will fully address, vaccines represent an important part of the solution. We are proud to develop vaccines to help fight the diseases that have become increasingly resistant to treatment with antibiotics. And we look forward to sharing more updates on our earlier-stage pipeline over the course of the year. From a financial perspective, we substantially strengthened our balance sheet, raising approximately $545 million in net proceeds in a follow-on financing last April. And then added another $816 million earlier this month. Pro forma after this most recent financing, we had over $2 billion in cash and investments as of year-end. This financial strength provides us the capital to fund the company through several important milestones over the next few years, which Andrew will highlight later.
I’ll now turn it over to Jim who will provide more details on our PCV programs and strategy. Jim?
Jim Wassil: Thanks, Grant. I’d like to start by reiterating my developing broader coverage vaccines to treat pneumococcal disease matters. Despite the widespread administration of effective vaccines, the global impact of disease remains significant and is associated with high case-fatality rates, antibiotic resistance, and meningitis. In the U.S. alone, the standard of care pediatric and pneumococcal vaccines cover only approximately 30% to 50% of circulating diseases. As a result, the public health community continues to affirm the need for broader spectrum vaccines to prevent IPD. We designed our PCVs to expand coverage and still include all of the serotypes covered by the current marketing vaccine that were most prevalent when these vaccines were originally developed.
The ability to both add newly circulating strength and maintain pressure on previously circling strength is critical from a global health perspective. Based on the totality results from the VAX-24 adult Phase 2 program that Grant referred to earlier, we believe we have the opportunity to set a new bar for pneumococcal vaccines by delivering broader coverage and higher immune responses relative to conventional PCVs. Following the completion of the Phase 2 Adult Program, we had a successful end of Phase 2 meeting with the FDA, focused on the VAX-24 adult Phase 3 clinical program. We believe there is agreement with the FDA on the clinical design of this program, including the approximate overall number of subjects, the primary and secondary endpoints for the pivotal non-inferiority study, as well as confirmation that the planned immunogenicity analysis are sufficient to support licensure and an efficacy study is therefore not required.
Regardless of whether we advance VAX-24 or VAX-31, we expect either Phase 3 program to include up to five studies to support licensure and the broad label. Additionally, as part of the ongoing safety focus discussions, we received encouraging input from the FDA regarding the VAX-24 adult licensure requirements. We are afforded this dialogue under the VAX-24 adult Breakthrough Therapy designation and expect to seek additional CMC-focused input from the FDA as it continues to prepare for an adult Phase 3 program for either VAX-24 or VAX-31 and future BLA submissions. For VAX-31, we are thrilled to see that our Phase 1/2 adult study progressed from IND acceptance to enrollment completion in approximately three months. In total, the study enrolled 1,015 adults, aged 15 or older and is evaluating safety, tolerability, and immunogenicity at three doses.
Low, middle, and high compared to Prevnar 20, which I will refer to as PCV20. Similarly to the criteria for the VAX-24 adult Phase 2 program, the VAX-31 study will compare the opsonophagocytic activity or OPA and IgG responses compared to PCV20 for the 20 serotypes in common. And for the 11 serotypes you need for VAX-31, the study is evaluating the percentage subject to achieve a fourfold rise in OPV titers which is the established precedent and a basis for approval. Based on the preclinical data for VAX-31 and clinical data for VAX-24, particularly the mixed dose arm for both adult Phase 2 studies, we are optimistic about the prospects for the VAX-31 data. Recall that in the mix those aren’t from the VAX-24 study, we simulated the amount of carrier protein that is in the VAX-31 middle dose.
We believe those immunogenicity results give us a preview of what we might expect for VAX-31. If we see results for VAX-31 that are comparable to those from the mixed dose arms of the VAX-24 study, in which all the three serotypes hit the non-inferiority endpoint. We believe that would be a very positive amount. Going to our expectations for VAX-24 Phase 2 adult program, for the VAX-31 study upcoming readout focuses on the OPA geometric mean ratios for each serotype rather than the confidence intervals. Because this Phase 1/2 study will be smaller in size than the Phase 3 study, you can expect the confidence intervals to be wider. It’s very possible that several may cross the 0.5 non-inferiority threshold. Yes, the GMRs are 0.6 or higher for each serotype in the study.
Prior Phase 3 studies have shown that these ratios are adequate to achieve the non-inferiority threshold. When considering the historical presence for broader spectrum PCV candidates, our focus has been on the important societal benefits of extending disease protection, which is probably helpful in line for all prior PCV programs that have been approved. Regulatory authorities have accepted generally lower overall immune responses and some met non-inferiority endpoints versus the standard of care. We believe, however, based on our VAX-24 data that our carrier-sparing platform has the potential to change this historical pattern by both extending coverage and maintaining immune responses. With VAX-31, we expect to increase disease coverage by 45% influenced over the standard of care in adults today, which is significantly greater than the increase in recoveries presented by prior programs.
We believe this level of improvement will be strongly considered by regulators in their assessment of the potential public health benefit VAX-31 may provide. As our adult programs continue to advance, we are also pleased with the progress we’ve made with our VAX-24 program in infants. VAX-24 has a potential best-in-class profile in this population. And we are excited to be nearing enrollment completion for our infant Phase 2 study. Given the size and global nature of the infant market, we are particularly excited about the primary and booster data readouts expected in 2025. We believe these milestones along with the VAX-31 adult data readouts expected in the third quarter of this year will further define the full potential and magnitude of the PCV opportunity for Vaxcyte.
