Vaxcyte, Inc. Common Stock 12th Annual Cantor Fitzgerald Global Healthcare Conference

Great. Thanks, Carter. Thank you for having us. Thank you all for coming. A very exciting moment for Vaxcyte. We have our VAX-31 adult phase III pivotal study reading out by the end of October. We tightened up the guidance for that late last week. It was originally fourth quarter. We've tightened that up to be by the end of October. If you're not close to the story, the pneumococcal class has been historically the largest segment of the vaccine industry. It has about an $8.5 billion annual run rate. The adult segment is a $2 billion-$3 billion market opportunity, but growing quite quickly. We have been working on a new generation of pneumococcal conjugate vaccines that leverage the underlying platform technology that we have control of at Vaxcyte.

It allows us to perform site-specific conjugation, so we can actually leverage the same components that have made up this class that has turned into a wildly effective way to prevent pneumococcal bacterial infections. We have produced data thus far through phase II clinical development that has shown unprecedented findings. What I'm talking about is this is a class where the vaccines are so effective that the included serotypes are effectively taken out of circulation, and in their place, other serotypes begin to circulate, which is what drives the need for broader spectrum vaccines. But if you take the older serotypes out, they return also. So you have to keep the pressure on the old ones while rising to the occasion of the new ones. That is what has driven what was originally a 7-valent vaccine to a 13 to a 20.

Unfortunately, the exchange has been broader coverage at the expense of lower immune responses. What we were able to show in phase II clinical development with VAX-31 was for the first time, we could show that we could provide much broader coverage and actually improve the underlying immune responses when we compared VAX-31 to Prevnar 20. So that was the basis of how we moved into phase III clinical development. In the meantime, a 21-valent vaccine, I'm sure will come up in the course of this conversation, has come out. So our phase III study that we call OPUS-1 will read out by the end of October. We'll have data for VAX-31 compared to both the 20-valent and the 21-valent that are out there. So very exciting time for the company and eager to tell you more as the conversation unfolds.

Yeah. This is a class where, as I have just set up, you are always trying to substantially increase coverage relative to what is available today. As I described the dynamic historically, there has been this exchange to get broader coverage at the sacrifice of lower immune responses. Yet, that has been readily accepted. Every successive class of pneumococcal conjugates have had at least one miss on the endpoints where you are showing non-inferior immune responses to the overlapping serotypes while trying to ensure that the incremental serotypes have at least a particular threshold of immune responses. The bottom line is, perfection is not the price of admission in this class. The way that the regulators manage this class is with a lens on the totality of the benefit that the newer vaccine can provide over and above and in relation to the current standard of care.

For us, we are comparing VAX-31 to two different vaccines, one of which we have 10 more serotypes, and the other for which we have 11 more serotypes. The way that we think about this is it is the case that we have guided to one miss relative to the 20-valent comparator, and five misses relative to the 21-valent comparator, yet when you have 10 or 11 more, it means that we are expecting to have a much better vaccine and totality of argument coming out of that data. Our view is in looking at the historical precedents, and I will just give you one of them so you can put a point on it. When Prevnar 20 was approved in infants, the standard of care at the time was the 15-valent that Merck had gotten approved, and that product had six failed non-inferiority comparisons.

Yet the regulators were still willing to give the full license to all 20 vaccine serotypes because there was a belief that the threshold was exceeded with regard to what would continue to be a protective effect, and the benefit of the broader spectrum vaccine warranted its approval. Sure enough, that product now has 90% market share relative to the 15-valent. We expect to have a stronger case than that with regard to the number of misses relative to makes given the expanded coverage and so many more serotypes on top of either of the competitive products.

Well, yeah. I think you're raising a couple of important points. The question is how translatable has the treatment for the infant vaccines been applied relative to how they might be applied in the context of the adult setting? I would say that the test that was passed when the situation that I just described, when Prevnar 20 had six of these misses relative to the 15-valent vaccine. How does that test compare to the adult situation? I would argue that that's a more important miss in the infant setting because that particular miss is on a well-defined seroconversion threshold. Without going into all the gory details, either you're above the threshold and that child is protected from disease in their first year of life, or you're below the threshold and they're not protected.

In that case, they actually had a meaningfully higher number of infants that were not protected relative to the comparator. Yet the totality of the evidence still warranted allowing for that exposure for the infants who would receive that broader spectrum vaccine. In the case of adults, we're talking about a different endpoint. It's a validated surrogate immune endpoint that correlates with the protection against this disease, but it's not a bright-line threshold that defines seroconversion. This is an average immune response compared across two different vaccines.

In the case of each of the misses that occurred in the adult space, the reason the FDA has allowed those serotypes to be included is because even though there might have been a statistically significantly different magnitude of average immune responses, the threshold that the serotype responses were at were believed to be well above what would be expected to be a protective threshold. That has been the case in each of the situations for Prevnar 20 and for CAPVAXIVE.

In the case of VAX-31, we have the benefit of a phase II study for which we showed extremely robust immune responses for which we would expect, even with a missed non-inferiority comparison that we're guiding toward, the threshold would be exceeded in ways that the regulators would be reassured that it would be very unlikely that you'd see breakthrough disease, even with a lower average serotype response on a particular serotype, particularly in the context of the total amount of disease that a 31-valent vaccine would provide relative to a 20 or 21. To be specific, the 31-valent vaccine that we have in development covers 95% of the circulating disease, whereas the 20-valent from Pfizer covers around 60%, and the vaccine from Merck covers around 80%. So we have a material improvement on top of any of these prospective non-inferiority comparisons.