We're going to get going with our next company presenter at the B of A Annual Health Care Conference. We're joined by Vaxcyte and CEO Grant Pickering and Andrew Guggenheim, CFO. So, gentlemen, thanks for joining us. Looking forward to a discussion ahead of a very important year for you guys in terms of further validating your vaccine programs for pneumococcal disease.
I thought maybe a good place to start was just you operate in a space not typically trafficked by a lot of biotech companies, to say the least. It's typically reserved for a lot of deep-pocketed pharma, a lot of, I'd say, probably high-capital commitments on the upfront side. If you've got a great vaccine with an ACIP recommendation, it sells itself, probably less capital-intensive on the back end, unless you look to be a global supplier of the market.
So maybe just talk a little bit about what makes your company unique and able to not only exist, but really thrive so far as a company in this space. You've turned over two data sets, really, with Vax24, and we're going to get into Vax31. But maybe if you can kind of lay that foundation, and then we'll jump into some more detailed questions.
Yeah. Well, Jason, first of all, thank you for having us. Delighted to join you guys here in Las Vegas again. Thank you all for coming. Yeah, I think you could probably break the history of Vaxcyte down into two discrete chapters. There was the opportunity itself, and then the realization of the opportunity as the companies progressed.
I think that first part is characterized by how attractive this class of vaccines actually is. So we've all become vaccine experts over the last five years. And what is a hallmark of this class, and I'm talking about pneumococcal conjugate vaccines, is the durability of the class. It's a very steady class. Every birth cohort gets these vaccines. Older adults now get these vaccines, certainly here in the U.S. and beginning to happen in other developed countries.
That means you've got not only a stable market, but a very large market. So it's about an $8 billion annual run rate for sales of these vaccines. And the development of this class is also more efficient than some other vaccine classes, where when you're developing a completely novel vaccine, of course, it's interesting to show antibody responses in people.
But you don't know if you have a vaccine until those antibody responses actually correlate with protection, which you won't find out for many years after running a clinical study. So that ends up making it very capital-intense and very risky for earlier-stage investors. And in this class, the approvals are now based on validated surrogate immune endpoints, which are those antibody responses.
The reason for that is the original efficacy studies that were run showed very clearly that if you got antibodies of a sufficient level, it protected. These are extremely effective vaccines. That made for a very interesting opportunity when we recognized that we had a new form of chemistry that could allow us to leverage the same basic immunogens that have fueled this class, but put them together in a way that could allow for broader coverage, which is really what drives the bus in this class.
We'll get more into that later. We thought we had a really interesting opportunity with a very important new technology. The second chapter of this company and this story really came after those clinical data readouts that we obtained over the last couple of years.
So we went from private capital to now having been a public company for four years, where I think a lot of long-term investors see the potential to build a really important new class of pneumococcal conjugate vaccines around a new company. And so the underlying theme to your question is access to capital. So this is an expensive class. All vaccines are successful only if they're able to supply the market .
T he investment associated with producing global supply is quite intense. So we have raised a substantial amount of capital. It's the access to that capital that has allowed us to continue to prosecute these vaccines in ways that we think we're maximizing value for all involved and will ultimately help us deliver these vaccines as broadly as possible.
Yeah. So most biotech companies typically get seeded enough capital to run a couple clinical trials, right? And that's the extent of the leash that they get. You guys talk about the mix of investments you've made from a clinical trial perspective versus the manufacturing investment that you've made, the dedicated suite you have with Lonza now. Just give us a little bit of flavor for where you're at with that and what that affords you now versus what will require further investment.
Yeah. And I think to play off to Grant's answer, I mean, this is a space where early clinical data has remained consistent through later clinical trials. And if you look at prior sponsors, 100% of companies who've shown positive phase II data have gone on to get positive phase III data. And so the level of confidence that we now have based on this positive phase II clinical data, and we have two data sets as we've talked about, gave us the confidence, and I think the confidence of investors, to make the investment perhaps earlier than one otherwise might in manufacturing.
That's important because this is a huge market. So you need to have the product available to supply the market. It's important because to garner the recommendations from the recommending bodies, you need to demonstrate that you can deliver that capacity.
We made a decision a couple of years ago. We were working on this, but ultimately made the decision late last year to execute a new agreement with Lonza, we think the world's leading CMO with whom we've been partnered for the last seven or eight years. This is a new investment with them under which we are building out a dedicated custom suite within their kind of marquee Ibex complex in Switzerland to give us the capacity to supply both the global infant and adult markets in the developed world.
That's an effort underway. We've guided to $300 million-$350 million in spend over the next couple of years to do that. We've been fortunate to have had the clinical data, as I said, to give us the confidence to make that investment. That's to satisfy the later launch.
We're separatel working on completing out the readiness for our initial launch in the adult market, which is principally in the U.S.
Yep. OK. You mentioned about an $8 billion pneumococcal market. How do you see the space evolving in the next few years ahead of your launch? There's obviously some competitive entrance. And what would you see as validating, generally speaking, for the more coverage is better hypothesis, which lends to your story?
Yeah. Maybe I'll start there just on the market. $8 billion market. That's comprised about $6 billion, the infant market. And the infant market is larger for two reasons. One, it's a global market, really, in both the developed and developing world. These are recommended for all birth cohorts. And it's a multidose market. In the U.S., infants get four doses in their first year of life. The adult market is the balance of $2 billion.
Historically, that has been a U.S.-dominated market, and it has been a one-dose market. So if you look at projections by a number of third parties, pretty consistent estimates that the growth of the global market is going to increase quite substantially from the current $8 billion to $12 billion to $13 billion over the next several years, driven by several reasons.
Most of that growth in the adult market, an expectation that ultimately the recommendation for adult vaccinations, at least in the U.S., will drop from age 65, where it is today, down to age 50. That opens up, of course, a larger market. You have far more adults entering their 50s than you do their 65s. And then that likely would also convert the adult market from a single-dose market to a prime- boost market, further growing that market.
T hen outside the U.S., as I mentioned, historically it's been a U.S.-dominated market in the adult population. There is an expectation, and we're now beginning to see countries outside of the U.S. make recommendations for adult vaccination, Germany being the first example a couple of months ago. There's discussion that's going to happen in the U.K. as well.
So there is an expectation that we'll begin to see recommendations around the globe. And then the last thing I would say, and this is applicable to both the adult and the infant markets, when new broader spectrum vaccines are introduced, you typically see premium price afforded to those vaccines, given the improved kind of health economics that the broader valent vaccines address.
So that's, I think, just the size of the market and the expectations. And Jason, to your question about the dynamics of the market, it historically has been the case for the last 20+ years that broader spectrum vaccines win the market. We do not see that dynamic changing. There are some interesting things afoot in the adult market today that are probably worth discussing.
But overall, we continue to believe, and I think history has proven, that broader spectrum vaccines garner the overwhelming market share, either because of the ability to obtain the preferential recommendation from the various bodies or simply because in physician practice they move to the broader spectrum vaccine.
Yep. That's a good segment, right? So adult market has some growth levers to it as we look ahead. Maybe just curious to get your perspective. Merck's V116 has a PDUFA, has an, I believe, an ACIP meeting shortly after that. What would be your expectations to come out of, I guess more importantly, I guess, the ACIP meeting at this point, either be it from a recommendation for more coverage gets prioritized and/or potential for ACIP at that point to even recommend a drop down to 50, or is that something that you'd envision happening much later?
Yeah. So that ACIP meeting is coming up at the end of June. So it will be upon us quite soon. And just prior, the last ACIP meeting, they already set the stage for what we think they're going to do at this next meeting. And I think it's pretty clear that well, before I say that, usually the most important thing to obtain in this class is a preferred recommendation. Because if you get the preferred recommendation for your vaccine, there is no competition. It's just rapidly adopted and replaces whatever the current standard of care had been.
Heading into that last meeting, the open question was whether or not the ACIP would lean toward granting this new vaccine, V116, to the extent it's approved, a preferred recommendation. But the conversation was very clear. They weren't seriously considering that.
The bar for a preferred recommendation is driven by one of two directions, either substantially improved efficacy or substantially improved coverage. As Andrew had alluded, coverage really has been king in this class. So while V116 does have broader coverage in this moment, the problem and the center of the debate at the ACIP was around the following issue, which is, in exchange for broader coverage, the design of that vaccine excluded 10 strains of the bacteria. Those 10 strains of the bacteria are the strains that have historically circulated. They've been most problematic historically.
But they've been under control because we've been vaccinating them on a regular basis. So they've been suppressed. If one was to switch over to V116, the risk is that those strains would reemerge.
We've seen that in one of a few instances where we've seen a similar set of circumstances. So the belief is still there that if you can provide broader coverage, and it has to be substantially broader, in combination with an ability to continue to suppress those older strains, that's the kind of profile that I think would resonate with them for a preferred recommendation.
But unfortunately, we're just not there yet with the programs that are at that point. And then so that was the first key topic. But then, as you pointed out, there's also the notion of bringing these vaccines down to adults when they turn age 50 instead of the past approach where we're just giving these vaccines to adults when they turn 65. So they did deem that to be a probably yes sort of decision.
The question is, when will they take that decision? It's hard to know whether or not they'll make that recommendation at this upcoming meeting or if they'll wait and see how the market evolves in the context of this new vaccine presumably being introduced into the regimen and see how things play out from a usage perspective.
The other interesting dynamic at the ACIP, if you've listened in or read the transcripts, they get very nervous about how confusing these regimens can be for doctors. We've got a scenario where the RSV vaccines are being integrated into practice. The idea of bringing this class of vaccines to a much larger swath of the population, we're talking about 65 million Americans, with kind of a jump ball between Prevnar 20, which is today's standard of care, and V116 could create some serious confusion.
I would imagine that will be part of the debate when they meet at the end of June.
Great. Maybe we could shift to Category Killer.
I think I know what you're talking about. Yes. That is an affectionate pet name for our vaccine, Vax31. So the dynamic that I described was very much in mind when we designed this vaccine. But we have 31 different conjugates in Vax31. It covers 95% of the circulating strains in adults here in the U.S., even a bit higher in Europe. We've maintained those 10 strains that have historically circulated. So as to ensure that we deliver what not only the ACIP is looking for but what we think will have the greatest impact on global health, which is addressing the largest amount of circulating disease possible while continuing to suppress those historically problematic strains.
So yeah, that's Vax31. The program is at a really important inflection point. We completed enrollment in a 1,000-person adult clinical study in January.
We've announced publicly that we expect to see the results of that study in the third quarter. So it's going to set up for a really, really important readout for Vaxcyte later this year.
You talked a little bit about the translatability of these phase II adult data sets to later clinical success. Maybe talk a little bit about the rabbit model data that you looked at for Vax24 that were largely mirrored in the human experience. Then you went to Vax31 with a similar animal model. Just what you draw from the animal work that's been done on Vax31?
Because one of the most common questions I get from investors as well, it's kind of hard to diligence Vax31, right? And you have some animal data, and then you have some experimental work you did with a mixed dose to mirror, I guess, the amount of protein carrier that's employed in your Vax31 formulation.
Maybe just it's a long-winded way of asking about how you feel about how de-risked this is and what you've been able to learn so far about this program.
Yeah. I mean, you've touched on the high points. So Andrew was talking a bit about the continuity in this class. It's been quite remarkable. So this class of vaccines has been around for 24 years. And there has been remarkable consistency between the design of these vaccine immunogens and not to geek out on you guys.
B ut this class of vaccines is characterized by these inter- strand cross-linked matrices of the polysaccharide sugars and a protein with T-cell epitopes on it. And if you can make those conjugates and characterize them in a consistent way everybody uses the same means the translatability between those constructs and immunogenicity in animals in this rabbit model and then immunogenicity in people has been incredibly consistent.
When you can make them in the right form, put them into rabbits, and you can show that they're boostable, you give the rabbit two different doses, and after the second dose, they get a much larger immune response after the first, that's showing that you're getting memory, you're getting a prime, you're getting a boost. And when every developer that I'm aware of has shown that data in rabbits and taken those constructs into people, they've got really good immunogenicity in people.
That was kind of what we started with 10 years ago. And in our own experience, it's entirely held. So for Vax24, we iterated and maximized immunogenicity and stability preclinically using rabbit data. We took those best of the best conjugates into the clinic in the form of Vax24. And I'm sure most of you have seen those results.
We went 24 for 24 in terms of hitting the minimum hurdle for approvability in this class and did that in the context of a broader spectrum vaccine in ways that no one has ever been able to produce. And the reason for that is our unique chemistry and our ability to use a more sparing amount of the protein carrier.
So the translatability between rabbits and humans has been extremely reassuring. And now we have the benefit of clinical data for 24 of the 31 conjugates that are in Vax31. So all 24 that we've already had good rabbit and human data are now in Vax31 along with 7 more conjugates. And we've done likewise in terms of characterizing all 31 of the conjugates, confirming their immunogenicity in rabbits.
We have this data from the Vax24 studies where we not only showed that all 24 could look great at a single dose, but when we doubled the dose of seven of them, that actually mirrors the cumulative amount of the protein carrier that's in Vax31. That cumulative amount of protein carrier has been the culprit that has held other developers back because they have to use more of the protein than we do using our chemistry.
T hat mixed dose data, as you pointed out, is another level of reassurance that we have heading into this clinical data readout.
The phase II data readout, roughly 1,000 adults, I believe. On the one hand, your active comparator is PCV20, but you want to do more than beat PCV20, right? Because you have to make a decision between Vax24 and Vax31 and what to advance. Talk about how you think through that. You get the question a lot about sort of defining success. I'll leave that to you.
Yeah. I mean, I think at its highest level, this may be a simple answer, but we're looking for data that we believe in a phase III program would represent an approval profile. And I think there are lots of ways to win in this study. So yeah, we have 31 conjugates. For 20 of those, we'll be comparing to PCV20. And then we have 11 incremental serotypes.
The bar for those incremental serotypes has historically been easier to hit for other developers. And we saw that in our Vax24 study as well. So we feel confident in our ability to deliver on the requirement for the 11 incremental serotypes. And then on the 20 common serotypes, we're comparing to PCV20. We did that comparison in the Vax24 study as well. Admittedly, now we have more serotypes and therefore more protein.
But again, this mixed dose arm in the Vax24 study gave us insight. And so we'll be looking at the data and assessing this on a serotype-by-serotype basis. But do we see a profile that we think in a larger phase III study where your error bars are going to inherently tighten, do we think we would have a data set that would warrant approval. And as thrilled as we were to have gone 24 for 24 for the Vax24 study, as you well know, Jason, that necessarily wasn't our expectation going in.
So we feel quite confident in the prospects for Vax31. For 31, it's also not the expectation. That would be an absolute best-case scenario. But as this space has historically shown, that is not necessarily the requirement for approval.
For us, the consideration that we think is going to be really important is PCV20 provides disease coverage of about 65%. With Vax31, we'd be taking that up to 95%. So we're addressing 11 incremental serotypes and substantially increasing the disease coverage, which is going to be an important factor for us and ultimately the regulatory authorities as to how they assess the data from the program.
So even if you only had confidence in, say, adding a couple additional strains relative to 24, but you're adding it may not be to the level of immunogenicity with those other strains, you're giving something, right? So in its totality, does that sound like an advance relative to Vax24?
Yeah. I mean, the history of this space has been characterized by the following dynamic, which is the FDA is inspired to want to pull through broader spectrum vaccines to provide greater protection. But they realize, given today's technology that's on the market now, they've had to make some sacrifices, which is sacrificing lower overall immune responses for broader coverage.
And heretofore, that's been a good trade. So even when the current vaccines had been approved, they had missed on at least one of these non-inferiority comparisons on a conjugate-to-conjugate basis, and sometimes as many as six. And yet those vaccines have still been approved. They've still been recommended by the ACIP. And so the reality is no one's ever had what I usually call a dud in any of this class because of this ability to characterize the conjugates, confirm them in animals.
So you're always getting some immunogenicity, just not getting as much as they'd like. Overall, it's been a good trade. For us, with Vax31 to the scenario that Andrew pointed out, if we were to miss on a few of the non-inferiority comparisons, that would be par for the course in this class. The label would still include all 31 of the conjugates even if you missed on a few non-inferiority comparisons.
We're in a really good position. We've got Vax24 already with a very clear path to a phase III program that we believe would replicate the phase II results. Now the question is, how many additional strains will hit? As long as we see a path to a successful phase III program, we'd expect to pivot to Vax31.
I would just add that's the focus in this study. As it was in Vax24, it will be on the mean, geometric mean ratios, the point estimates, right? Because the study will be smaller in size than would a phase III study, we're focused on those mean estimates. And if we see mean GMRs that are 0.6 or higher, that would give us great confidence. Then a phase III trial, we would be able to hit the statistical non-inferiority standard, even though, as Grant said, the requirement isn't necessarily to go 31 for 31 in a phase III given the historical precedent here.
Well, let's say you see an outcome that you're very encouraged by with Vax31. How does that change the decision calculus with the infant program?
Yeah. The infant situation is a different one. For the adult programs, we're now presented with an either/or decision. So upon the Vax31 data, we would expect to choose to pivot to Vax31 or stay the course with Vax24. In the infant population, it's a different calculus. One, because the time frames for our two infant programs are different. If our Vax31 data are positive, we would expect to quickly stand up a Vax31 trial in infants.
But we need to show both immunogenicity and safety in the adult population before we can go into infants. The Vax24 infant trial is already underway. We completed enrollment earlier this year. We've guided to having the two data readouts from that study, the first by the end of the first quarter of next year, the second by the end of next year.
So that program is a couple of years ahead of the Vax31 study. So in the infant population, we expect to continue to stay the course with Vax24 and, if successful, have that be the first to market with Vax31 as a potential fast follower. But we absolutely would expect to invest in the Vax31 infant study to the extent we see the data, we hope, and expect to see in the adult population.
I see. So you'd basically kind of do redundant phase III investment in 24 and 31?
Yes.
Okay. With the mixed dose in Vax24, I think there was a mention of some diminution on some serotypes. How do you see that as a risk, if at all, in this study for 31?
Yeah. So in that mixed dose cohort where we doubled the dose of seven of the conjugates, we did see some impact on a few of the conjugates. They did actually have lower immune responses than they did in the 2.2 microgram dose across the board. So that didn't surprise us. We expected to see an outcome like that.
F rankly, that is the best indicator of what the Vax31 data could look like. And if we saw a similar pattern, we'd rejoice. That said, we'd be remiss to not have a look at those few strains and tweak them to the extent we think we can improve their immunogenicity. So we did that. So we think we have our best 31 conjugates at the best doses being studied across the three different doses we're testing. And we're hoping to see them shore up a bit.
But again, if those persisted, I think we'd still be in a really good place.
Okay. And maybe just the.
And I say that, sorry, just to point out, that's because of the ability to deliver on 95% coverage. In the context of that, that's how the agency thinks about how to pull these vaccines through. Your margin of error is driven by the incremental coverage you have an opportunity to provide over the standard of care. And when you look at the previous precedence, the amount of incremental coverage that Vax31 has an opportunity to provide is more than twice that of any other vaccine of late that they've considered.
So knowing that you've been able to miss a few strains in the past, we know we could miss on a few strains or more. We're not expecting that, but we know that could all work out for us.
Okay. Last question because we're almost out of time. You had a phase II meeting with the FDA last year. Can you just maybe share with us? There's been some discussion you showed superiority on certain shared strains relative to PCV20 and the ability to potentially work that into a clinical program and convey that to ACIP or doctors and how commercially important you think that might be?
Yeah. I would say really the objective here remains non-inferiority. That is the primary goal here. We're presented with a unique situation that hasn't been afforded to other developers because, unlike the historical precedent, historically, when one has expanded coverage, it's been an expensive immune response. We were able to expand coverage and see an improvement in immune responses in general.
But we should just remind ourselves that the goal here is non-inferiority. We may have an opportunity to demonstrate superiority. We've reached agreement with the FDA on what constitutes superiority. In terms of, Jason, its impact on clinical practice, it's hard to know because it's never happened historically. And we think, again, it's really all about a broader spectrum vaccine and reaching approval. That approval is really going to be driven by the non-inferiority requirement. And superiority would represent only upside there.
But if we have a broader spectrum vaccine that is approved, that should garner the overwhelming market share. It's unclear how much additional benefit one would garner by superiority.
Okay. We're out of time. Thank you, gentlemen, for joining us.
Thank you, Jason.
All right. Great. Thank you.