Well, thanks everybody for joining us for day two of Guggenheim's sixth annual Biotech Conference. I'm really pleased to be joined by the Vaxcyte team. To my right is Grant Pickering, and we also beside have Andrew Guggenhime, and Jim Wassil. So, really pleased to have the C-suite here today. But Grant, maybe you can just kinda kick us off with, you know, obviously a very successful launch of the Vaxcyte story, through and during the pandemic, which is pretty impressive, to say the least. You know, along with a number of successful financings, and, you know, an exciting story in the pneumococcal disease space. So, just maybe you can get folks caught up on where you are and where you're headed in 2023 or 2024.
Yeah. Seamus, thank you for having us at the Guggenheim Conference. We're pleased to be here. And yes, we took the company public in 2020. Very crazy time, as we all remember, and we stayed focused on our lead vaccines, which are pneumococcal conjugate vaccines, despite the overwhelming presence of the pandemic, just because we had real belief in our ability to bring out more broad-spectrum versions of these critical vaccines to protect the pediatric and elderly populations foremost. And, you know, to date, we've made great progress since that IPO. We were able to get into the clinic with our 24-valent vaccine, more recently with our 31-valent vaccine.
We're really gratified to see the hypothesis borne out, that we could develop broader spectrums of coverage and maintain immunogenicity, and in fact, increase immunogenicity relative to less broad-spectrum forms of these vaccines. So as opposed to COVID vaccines, for which the demand has waned, these pneumococcal conjugate vaccines are fundamental and are really the foundation for the class of vaccines and the business of vaccines. So we're very optimistic and excited about the opportunity to continue to advance these programs. We'll talk more about the details, but VAX-24 is phase III ready, and we're expecting to receive a large phase II readout for VAX-31 later this year. So real exciting time for the company.
Great. So maybe just as a sort of starting point, you know, let's talk about a little bit of where the pneumococcal market is today. In particular, you know, some of the interesting developments that we're seeing between Merck and Pfizer, VAXNEUVANCE versus Prevnar 20, in the pediatric setting. But there's also some potential new product coming to market from Merck with the V116. So just interested to see how you envision the development of the pneumococcal market going forward.
Yeah. So just to kinda acclimate people, the driver in this class of vaccines is coverage. And coverage is a challenge because when these vaccines are broadly administered to the population, those strains are effectively taken out of circulation, which is great. That's great news. The bad news is that in that niche that gets vacated from people having previously carried those strains of the bacteria, is replaced with additional serotypes and strains of this same bacteria, but they're slightly different. And so the pressure that has been on these vaccine developers is to preserve the strains that had been in the vaccine, that's the standard of care, but add coverage on top of that.
And unfortunately, this technology that both Pfizer and Merck share, has reached a point where they don't believe they can add additional coverage to these 20-valent vaccines. And so that's the promise that we have with our technology, is to be able to stretch the coverage well beyond 20 to 24 and 31. So that, that's kind of what the state of play is. And to put a point on it, coverage is really the key driver. So you referenced the 15-valent vaccine from Merck, which is called VAXNEUVANCE, relative to Pfizer's most broad-spectrum form of Prevnar, which is a 20-valent. That 20-valent has about 95% market share in the adult population, which really speaks to the criticality of coverage.
Got it. And a couple of the comments that Pfizer made on their most recent call was that, a market that I think historically was uniquely challenging, perhaps because of a view around, specifically with what's called, a herd immunity, that had been demonstrated with Prevnar 13. Now, with Prevnar 20, I think Pfizer recently talked about some markets opening up internationally, because of that broader coverage. Can you talk a little bit about that? And, maybe Jim if you wanna jump in.
Sure. So historically, there's been a push by Pfizer to try and get adult recommendations outside the US. What happened, though, was Prevnar came out in infants first, and they vaccinate for five or six years. Infants are the main carrier of this disease. They transmit the disease to grandpa. So what we saw was a 60% reduction in disease in adults by just immunizing infants. In the US, they said, "Well, there's still 40%. We need to continue to immunize adults and try and eliminate the disease." Ex-US, they said, "60% is good enough." Now, with a 20, and subsequently, with a 24 or 31, there's still a lot of disease left, and the adult vaccine is coming out first.
So now we were seeing the opportunity to try and reduce disease in adults first, and in fact, Germany just gave a recommendation to give all adults over 60 years of age, the vaccine for PCV20. So we should start to see ex-US, a significant number of adult recommendations as well, as you move forward.
Great. And maybe you can talk a little bit about your own approach. So 24-valent is sort of your initial shot across the bow. Great phase II data, highly consistent with, you know, the leading product on market. But, you know, 31 is awfully close behind. So can you talk a little bit about the update that you provided earlier this year? I think there was a little bit more information requested from FDA as it relates to your 24-valent before you start your phase III for that. But then the overlapping timing, I think, offers an important question around how to best deploy capital. Can you talk a little bit about some of the important decisions that you face this year?
Yeah. So, yeah, we gave a pretty comprehensive update in early January on our development plans for both VAX-24 and VAX-31. And, we've made it very clear that we have designs on bringing these vaccines to market. And, we believe that, you know, the best course of action to take is to do whatever we believe is necessary to maximize the probability of these vaccines being licensed. And so in that context, our CMC strategy has not changed, but we did make a strategic decision to hold on at least one of the phase III studies in order to incorporate the commercial material into the program.
For us, that meant sacrificing some time to a BLA filing for VAX-24, and it just so happened that, as you say, we had kept VAX-31 right on the heels of VAX-24. Now we find ourselves in a position where we are expecting data from our large phase II study for VAX-31 in the third quarter of this year. And if that data is as good as we hope, there's an opportunity to potentially pivot to that even more broad spectrum vaccine without paying a time penalty between the two programs.
And so I think we're in a really good position. We're taking the, the most conservative approach we think we can take to increase the probability of having these vaccines, to, to the public as quickly as practicable, but it also puts us in the position to potentially bring out an even more broadly protective vaccine than we might have imagined a few years ago.
Yeah. And Andrew, can you talk maybe a little bit about what you've actually done and accomplished on the preparation from a manufacturing perspective? I know that's been a unique focus of yours all along, and these are not, you know, cheap things to develop, and they're not simple either.
Yeah, I know. Certainly, it's been a huge focus for the organization, really, from the beginning. We've been partnering with Lonza for the better part of the last eight years now and recently enhanced our relationship with them. And to garner these preferential recommendations, which we think our programs warrant, we need to be able to demonstrate to the recommending bodies that we can deliver the supply required if we're fortunate to get those preferential recommendations. So we are working down several paths from a manufacturing perspective. One, of course, is ensuring we have sufficient supply for all the clinical trials, which we've been successful in doing. And we are preparing to do the initial launch, which we would expect to be in the adult population, which notwithstanding the recommendations coming outside the U.S., is still predominantly U.S. market.
Working and planning to launch out of existing facilities within Lonza, at which we've been operating to date. At the next step, of course, is upon the infant indication coming online. That is a global market, and it is a multi-dose market, so substantially larger in size. In this recent announcement with Lonza in October of last year, we are now beginning the work to build out this dedicated suite within the existing Lonza complex and working to put ourselves in a position to have sufficient supply, if and when we bring that infant indication online, to provide the global supply for VAX-24 and/or VAX-31 in the U.S. and all international markets as well.
Great. When we think about the, you know, kind of the next vaccine to come to market, maybe we can talk a little bit about Merck's V116, and, you know, how you see the upcoming ACIP potentially developing the market further. Both on, you know, sort of the positive side of things in terms of, you know, potential market expansion, but also on the competitive landscape side of it, you know, if it, if it does impact you in one direction or another.
Yeah. So, Just a little bit of background on how this will play out. V116 PDUFA date, they said, is in June. The ACIP has three meetings every year. One is in June. So in June, after presuming that V116 gets approved, they will vote on how to incorporate that into the schedule. What that means is, their upcoming meeting in February, they're going to have a discussion on what they're thinking. So we'll get an early read, excuse me, on how the ACIP will consider incorporating V116, if it gets approved. I'm sorry again. So what's happening right now is working group, there's called a pneumococcal working group. They're looking at all the data, they're making a decision, and sort of what our expectations are, they're debating two scenarios.
First one, that you give PCV20, followed by V116 a year later, or the other one is that, that you just basically recommend that the physician can decide PCV20 or V116. If it's the former, you know, obviously, you know, that, that gives you the best clinical benefit. You get to continue to immunize against the strains that are under control, and you broaden the coverage, and you actually have improved immunogenicity in the overlapping strains. That will have the best clinical outcomes overall.
However, there is, you know, part of the group in this working group is saying, "Should we add two vaccines, increase the overall cost, and is the incremental cost worth the benefit of the clinical reduction?" So I think we'll see in February where this working group has landed, and but it'll give us a nice foreshadowing as to what the vote will look like in June.
Got it. Okay. And in terms of the relative dynamics, one would sort of say, "Okay, you can have both 24 and 31, as the opportunity for Vaxcyte going forward." The other one, which some have espoused, is that actually the best approach is really to just go straight to 31. You know, maybe you can help us understand a little bit of both of those scenarios. What are the, you know, sort of realistic outcomes? Because 31 would have the coverage of all of the above.
Well, I think, you know, we'll see the data soon enough for VAX-31, and if it's as good as we hope, as I think I alluded to earlier, we wouldn't have to pay a time penalty, based on our expectations to pivot from VAX-24 to VAX-31 in adults. So with the right data, that would be an obvious choice, and that vaccine will cover 95% of the circulating disease in the U.S. It'll cover 98% of the circulating disease in Europe. And as it relates to the vaccine Jim was just talking about that Merck is working on, you know, we are continuing to preserve coverage of 10 strains that have historically been the most problematic strains in humans. They've taken those 10 out, so we have expanded coverage over them, and we're continuing to.
We expect to be able to continue to maintain protection against those strains that have historically been problematic. So yes, that is hands down a winning vaccine. So that would be the expectation with the right data. That said, in the infant indication, VAX-24 is in a large phase II study in infants and has a head start on VAX-31, and we don't have an ability to close the gap in infants the way we did in adults. So we can imagine a scenario where we bring two different vaccines to two different indications, but both of which would have best-in-class profiles.
Great. And maybe we can talk a little bit about the profile of 31 that you hope to see. Every time we've come up to a data set for 24, and I'm sure it'll come up on upcoming questions, so I'm going to ask it now. Help us think about, you know, what are the relative influences on, you know, demonstrating non-inferiority, you know, versus the existing strains, you know, with 31. Obviously, Prevnar 20 provides a really good backdrop, you know, for the performance of your product. But just wanted to get a better understanding.
I think historically, we've sort of had an expectation with 24, one or two serotypes or three serotypes maybe coming in non-inferiority, but that never happened because you had superiority and consistent non-inferiority demonstrated, so never saw inferior strains. You know, so maybe you can just help us level set that a little bit as we head into 31.
Yeah. So, the backdrop is that the regulators have been trying to pull through more broad-spectrum forms of the vaccine while giving enough confidence that the previous strains will maintain their controlled status, and that exchange has allowed for even those. So, you've got a more broad-spectrum vaccine compared to the standard of care vaccine, which is less broad-spectrum, and across those common strains, you only have to show non-inferiority. Non-inferiority was a good enough standard in the context of providing a more broad-spectrum vaccine. So much so that with every vaccine that has been approved, that has more broad-spectrum coverage, there has been at least one inferior strain in the common strains to as many as six inferior strains, and that was still an acceptable trade to the regulators in order to provide more broad-spectrum coverage.
As you say, Seamus, until we came along, that was the standard trade. We, so far, in our phase II studies for VAX-24, actually, for the first time, we're able to expand coverage and not just hit that non-inferiority comparison on the common strains, but in many cases, actually showing superior immune responses across the common strains. It does set us up to have an unprecedented situation where you're pushing coverage and improving immune responses. If we were to see that again with Vax-31, obviously that would be a real hallelujah moment.
But the reality is, the way this decision gets taken by the regulators is the degree to which you're increasing coverage is really what drives the margin of error for which they're willing to accept as it relates to potential inferior strains relative to the standard of care vaccine. So when we're pushing coverage with VAX-31 from what today's standard Prevnar 20 covers, which is 50% of the circulating disease, to as high as 95% with VAX-31, you know,
I think that we'll have a really strong case, even if we were to see a few strains for which we were technically inferior. So yeah, I think that based on the data we've generated in the VAX-24 phase II studies, for which in one of the cohorts, we did actually model the cumulative amount of protein carrier that will be in VAX-31, which is the primary culprit that inhibits these immune responses. That gives us a lot of confidence that the sort of profile we'll see coming out of this phase II study ought to be really encouraging.
Got it. And any dynamics with V116 in terms of, the ACIP decision and then ultimately FDA's guidance in terms of how a phase III program might need to be executed? Do you think that 116 may be, may be necessary to incorporate into a 31 program?
The good news is we'll know. So just the timing that Jim highlighted, you know, we'll hear from the FDA in early June. We'll hear from the ACIP in late June. So prior to starting either the VAX-24 pivotal phase III study or the VAX-31 commensurate study, we'll know where things have fallen out. We already know that we can compare to Prevnar 20 very favorably. The immunogenicity results that Merck has put out aren't really meaningfully different from a magnitude of immune responses. So I think we, you know, have optimism with either comparator, but historically, it's only been a single vaccine comparator. So, you know, we wouldn't expect to have to compare to both if both vaccines are available, but we'll know that soon enough.
Got it.
Technically, we've already had an end of phase II with VAX-24 and have agreement on our comparator as well.
Got it. Okay. So that's helpful, a helpful starting point.
Yeah.
In terms of, you know, just what's necessary, you know, from a... You know, I know there's a lot of questions, and a lot of important dynamics around manufacturing and what the regulators require. Can you just help us understand a little bit of, you know, what it is that is required and kind of the complexity that goes into things like lot-to-lot consistency studies, particularly for conjugate vaccines, in this space? I think there's maybe. Some investors have raised, you know, maybe not necessarily concerns, but just don't feel fully educated on that.
So, I mean, with vaccines, the saying goes, your process is your product. In many cases, you know, with a drug, you can test the final form, and you've got a chemical entity, and you know what it will do. The biologic, the three-dimensional construct is extremely important, so making sure that you maintain the immunogenicity means that you've got to do a lot of work to validate your process and your assays, more so than a pharma product. So we knew this. We started on this even before we had our first data readout. Obviously, with 24 and 31, the amount of process and assay validation is substantial. We've gone with a platform process in terms of how we manufacture, so we keep consistency between each of our polysaccharides, how we manufacture.
That helps with our workload for process and assay validation, but nonetheless, that's really what we need to do. We've been moving along as quickly as possible. We started before our data readouts, and for us, it's more or less just trying to get the volume and execution of data available and then lock our final process, manufacture three batches, which is a requirement for our lot-to-lot consistency, and demonstrate that in the clinic. We're, I'd say, well along the way of that course, we've had some feedback from the FDA that confirmed what we were doing was acceptable. We still have some things that we need to do, but essentially, we're comfortable with where we're at.
Great.
Maybe just one comment on top of that, which is, you know, this has really been a bit of a black box because most of the major companies don't speak of this part of the equation at all, and most of the regulatory correspondence is redacted. So I think one of the things that we've been able to talk about that's reassuring to people is that this class has been characterized by physico chemical assays that have been able to assess the three-dimensional constructs of these conjugates, and those ability to characterize these conjugates has correlated historically with their immunogenicity responses.
And even though we're doing a few things slightly differently than the other sponsors, many of the things we're doing the same. So we're able to leverage the same physicochemical assays to assess our constructs, which does give us a leg up with regard to the expectations of the regulators, because they're seeing the same methods of assessing these conjugates that they've seen with other sponsors.
So the choice of, I guess that maybe speaks a little bit to the choice of protein in the construct as well, which could be a layer of significant complexity for other competitors who also have already announced that they're seeing some additional complexity.
That's exactly right. So even though we're doing a couple important things different, we're effectively using the same immunogens that the immune system processes. You know, it's a diphtheria toxin protein carrier. It's the polysaccharide sugar from the coat of the bacteria. So these are the same components. We're just able to more nimbly dial the conjugation of them to the sites we'd like and to present those sites on the same immunogens to the immune system consistently. But other than that, what the immune system sees and the constructs themselves are extremely similar to the other approaches.
So rather than rebuilding the internal combustion engine from scratch, you've decided to just put more horsepower in it?
Okay, that's one way to look at it.
All right, fair enough. Well, I think we've covered just about everything. Thanks, everyone, for joining us, Grant, Andrew, Jim. And, you know, I think we're all looking forward to the upcoming weeks ahead. We didn't really have an opportunity to talk about the pediatric opportunity and why VAX-24, we think, is going to be a kind of mission-critical core asset in that space, and then VAX-31 could ultimately expand beyond that. But, you know, obviously, not enough time in 25 minutes- Yeah to cover everything to,
But I think you said at the third quarter, expected data from the VAX-31 study, and then the first data set from the infant study expected in the first quarter of next year are going to be meaningful readouts for the organization. We're looking forward to those.
Yeah. Thanks so much.
Thanks, Seamus.
Thanks, Seamus.
Thank you.