All right. Welcome, everyone, to Jeffrey's London Healthcare Conference 2025. My name is Roger Song, one of the senior analysts covering medical biotech in the U.S. It is my pleasure to have the fireside chat with our next company, Vaxcyte. Welcome, Grant and Andrew. Thank you, Roger. Pleased to be here. Awesome. All right. For people maybe not familiar with Vaxcyte, which should not be the case, but give us some maybe updated elevator pitch for Vaxcyte and where the current state of the union is. Yeah. If you're new to the Vaxcyte story, we are focused on developing a 31-Valent Pneumococcal Conjugate Vaccine. We have a proprietary foundational platform, which is a Cell-Free Protein Synthesis platform for which we are able to develop conjugate vaccines that are site-specifically joined in ways that we think we can increase coverage without sacrificing immunogenicity as it relates to pneumococcal conjugate vaccines, but also unlock novel vaccines, including a Group A Strep Vaccine we have in preclinical development. We're mostly known for the Pneumococcal Conjugate Vaccine franchise. Our 31-Valent vaccine has read out an extremely positive phase II outcome comparing to the standard of care 20-Valent vaccine. We're about to initiate phase III clinical development for that program in adults. We have a phase II program underway in infants with that same 31-Valent vaccine. Excellent. Okay. It is a very focused story for Pneumococcal Conjugate Pneumococcal Vaccine. We know this is an $8 billion-$10 billion growing market. Historically, it is a winner takes all. That is why people are really looking for best-in-class profile, which speaks to broadest coverage without sacrificing the immunogenicity. That is what Vaxcyte is striving for. Maybe just an additional kind of a high mark there. Let us just focus on the program. It is bifurcated by age group. One is adult, and then the other maybe elder adult, and then the other one is for the infant. Maybe focus on the adult. It is in late stage. You have been talking with the FDA, finalized the phase III, and you are about to start the phase III pretty imminently. What's the gating factor, outstanding steps you still need to finish before you can start the phase III? Yeah. We are pretty much there. We have guided to be initiating our phase III pivotal study for VAX-31 in December of this year. That is right around the corner. We will be making the announcement of that study as we vaccinate the first subjects in the study. You can look out for those details in relatively short order. I appreciate the assist on some of the comments. We are extremely excited and gratified to have seen the results we have seen with our 31-Valent vaccine. What usually characterizes a dominant position in this class is simply the coverage advantage that one vaccine has over another. What is unusual about what we have been able to do with our 31-Valent vaccine is not only expand coverage relative to the current standard of care, but also show better immune responses in a head-to-head comparison. Usually, you're sacrificing one or the other, and we have the benefit of that combination of both superior coverage and better immune responses. We are looking to replicate that in phase III. There are two standard of care vaccines that are currently available today. One is a 20-Valent. The other is a 21-Valent. What we have not said yet is which of those two, or if we will be looking at both of those in the phase III study, but that will be one of the things that we put out in the next month as we get the study started. Okay. Great. By the way, the profile is supported by the phase II data you already show. Pretty impressive data in the adult population. Okay. Good. Maybe just a reminder, I say this is an $8 billion-$10 billion growing market. Historically, the influenza is getting a bigger portion of the market, but adult is actually probably underappreciated by a lot of investors because it's growing, particularly with the recent ACIP kind of the universal recommendation. How do you think about the adult market for PCV, how big that could be, and then how much credit you should get that for? Yeah. So historically, the market has broken out with infants and adults. It's been about 80% infant revenue. So Roger has it right. It's an $8 billion run rate for the current market today. About 80% of that is in infants. 20% of it is in adults. The expectation is that the adult market is going to grow quite quickly. Historically, the U.S. has been the only country that has universally recommended vaccinating adults, and that's changing very quickly. Most of the developed countries, particularly those in Europe, Asia, Australia, have recently made recommendations for universal vaccination for pneumococcal conjugate vaccines for adults at various ages, usually 60 or 65 and up. In Pfizer's most recent quarterly update, their international sales of Prevnar went up 17% in the last quarter. We're really seeing a new wave of appreciation for the impact that these vaccines can have in adults. Looking forward, it's hard to know exactly how it will play out, but the expectations are that this market in the next five to ten years will grow from $8 billion a year to more like $12 billion-$15 billion. We could see that end up with somewhere around a 50/50 split between adults and infants ultimately. Having the best-in-class profile with our 31-Valent in adults is quite exciting given the anticipated revenue growth there. I might just expand on that, Roger. In the U.S. market, that's also one of the key drivers of the expectation of the growth in this adult market. Historically, the recommendation in the United States has been to vaccinate adults upon turning age 65. Just a year ago, they lowered that recommendation from 65- 50. Obviously, you have more Americans entering the age of 50 than you do 65. You have this bolus population of 63 million Americans that now become immediately eligible for vaccination. It is expected that that bolus population will be kind of vaccinated or a good proportion over the next several years. We think we'll be able to participate in that upon approval. We're fortunate to get there with our VAX-31 program. This market in the United States is setting itself up for what historically has been a one-dose market to a prime boost market where Americans would get vaccinated with the initial dose upon turning age 50 and would likely to be boosted as adults immunosense. At about the age of 65, this was discussed among ACIP about a year ago, and the discussion was tabled until broader Valent vaccines become available. We think the potential approval of our VAX-31 adult program would be the impetus for revisiting this discussion to boost adults. That is one of the three key drivers of the expected growth in the adult market. Yeah, exactly. The adult market is growing in a very rational way, right? With all the supporting evidence, there will become a bigger driver. I think start from 80/20 to 50/50. In a growing market, the adult market is a pretty sizable, already very sizable, and even more significant in the future PCV market. Okay. Good. That makes this adult program maybe more critical than investors thinking because people say, "Okay, infant is the bigger driver," but actually adult in the future can be an equally kind of important program. Okay. Got it. We have to ask this kind of because you're in the vaccine space, and we know a lot of FDA and the CDC, a lot of the changing the political and the policy environment. Anything recently you can give us some updates in terms of your interaction with the regulator or the policymaker, anything we should know? Yeah. I mean, maybe I can start and you can finish. Just by virtue of us being able to guide to initiating the phase III clinical development means that we've had those end of phase II conversations with the FDA. While we're stopping short of providing the finest detail of our phase III pivotal study that we're getting underway, what we have said publicly is that through the course of these conversations that we've had with the FDA, there's been no mention of any necessity for a field efficacy study or a placebo-controlled trial, nor have we had any suggestion that we would need to produce a safety database that would be out of the norm for programs like this. We are decidedly reassured that it's been primarily business as usual as it relates to the regulation of this class of vaccines. Yeah. I would just add the team with which we've been working at FDA has largely remained unchanged pre-administration to the current administration. Of course, we've been dialoguing with the FDA really since the IND submission a few years ago, certainly more recently in the context of this phase III trial that we're now poised to start. We haven't seen a material change in the team, nor in the tone and tenor of this conversation. There have been, there will continue to be interactions with the FDA as it relates to both of our adult and infant programs in normal course. Clearly, given the dynamic, we are investing to build relationships with folks in the executive branch in Congress, as well as the agencies, to continue to advocate and remind folks of the importance of vaccines and protecting our population as well. Those have been constructive dialogue as well. Certainly monitoring what is happening externally, but very involved from a government and public affairs standpoint to be apprised of what is happening as best one can, as well as, as I said, to build important relationships there. Got it. Yeah. Okay. Just back to one of the components you say you will be disclosing, which is the comparator for the phase III study. Did that really change any study design or the size of the study if you want to do one or both selections? Will that create more complexity? Or no matter which FDA you agree with, then it's not changing any kind of lack of success or the timeline or the size of the trial? Yeah. In the moment, the current standard of care includes either Prevnar 20 or the 21-Valent Vaccine from Merck, which is called CAPVAXIVE. For us, we believe we have the best-in-class vaccine. Our phase II study was conducted comparing VAX-31 to Prevnar 20. We showed on average a 25% higher immune response on the common serotypes. We know we have an immunogenicity advantage and a coverage advantage based on the phase II outcome. We're also able to look at the CAPVAXIVE pivotal studies for which they compared themselves to the same comparator, Prevnar 20. When we look at those relative immune responses, the advantage that we're seeing with the responses to VAX-31 only go up relative to CAPVAXIVE when we look at that sort of transitive comparison. Our view is that we could compare to either of those vaccines using very similar powering and sample size. The conventional cohort size in this class is around 850-1,200 subjects per cohort, and we've been guiding to staying within that range. Awesome. Great. Okay. We should move on to the infant program because you had a recent phase II from the VAX-24 and then with the full data from the PD3 and the PD4 phase II data. What did you learn from that trial and then most recent this full data, and then you applied the learning to the phase II VAX-31 program, which we'll have later. Yeah. Going back a bit, our first clinical program in our Pneumococcal Conjugate Vaccine franchise was a 24-Valent vaccine. We had originally gotten positive adult data for that program in late 2022. We then quickly advanced our 31-Valent program into adult studies and showed that with incremental conjugates, seven more, do the math, we could not only get broader coverage, but we were able to maintain high immunogenicity and even to push to higher doses to drive even higher immunogenicity. We had a lot of learnings as we were able to graduate from 24 to 31-Valent coverage in the adult category. In this moment, we have read out the VAX-24 infant study. We have already initiated the 31-Valent infant study. The big learning was that in this naive infant population, driving the right amount of protein carrier will deliver the right sort of prime and boost response that you want to see to deliver durable protective responses. We have already shown that our 24-Valent vaccine has shown adequate immunogenicity and an improved coverage profile relative to today's 20-Valent standard of care. Now, the opportunity for us is to graduate to the 31-Valent vaccine. We have taken certain learnings from the data that read out for VAX-24, and we've incorporated higher doses in the VAX-31 study that we think will put us in a position to graduate to the VAX-31 program to deliver meaningfully higher coverage than what we would be able to deliver with VAX-24. Given the sort of relative immune responses we've seen in adults, we have confidence that VAX-31, once it reads out, will give us an opportunity to upgrade to that program for phase three advancement. Excellent. Yeah. I think the phase II VAX-24, the purpose is always kind of to learn a little bit more about the profile and then to apply. Eventually, you want to do the 31 and then because this is establishing a bit higher kind of barrier of entry for the competitors. Yeah. The coverage advantage for VAX-24, it's only a modest coverage advantage. When you look at the 31-Valent and compare it to the 20-Valent that's currently available, you go from around 60% coverage of circulating disease to 90%-95% coverage for our 31-Valent vaccine, which would be a massive upgrade in terms of the amount of disease that we could prevent with that 31-Valent program. Excellent. Okay. You're running the phase II recently to add another high-dose cohort, which increased the likelihood of success for that program. What would we consider a winning scenario for that data result in the coming years? Yeah. I mean, the way we think about the composition of the vaccine is there are kind of three different buckets of the conjugates that are in the vaccine. We have 11 more serotypes in VAX-31 than we'll have in the comparator 20-Valent vaccine. Those should have a relatively straightforward opportunity to show the sort of effect that would warrant inclusion in the vaccine. That's a lower bar. There are those serotypes in the 20-Valent vaccine that are still circulating in earnest. We already showed with the VAX-24 data that we showed really good relative immune responses on those. It just so happens that it was the serotypes in the current vaccine, the 20-Valent, that aren't circulating where we showed weaker relative immune responses. If we could have picked anywhere we looked a little worse, those were the ones because they're not relevant if they're not circulating. By increasing the doses in VAX-31, we think we can do better from an immunogenicity perspective, but the only area for improvement were in those serotypes that are no longer circulating. What I would say is even if we had a few misses on these serotypes that are no longer causing disease in the context of a 31-Valent vaccine, that would be very much a winning hand on a relative basis. Every version of increasing coverage vaccines in this class in infants have shown some misses, but it's more than counterbalanced by the incremental coverage that the newer vaccine is able to deliver. We have that sort of same opportunity with us, but in the context of data that's already shown us, we're on track. It's just a question of how much of a coverage advantage will we be able to deliver. Excellent. Okay. This infant program is a multi-dose, right? They have a prime, three doses, and then booster, the final dose that we call PD3 and PD4. You say you will release those two data sets by first half of 2027. A strategic decision you will make is if you will separate them or report them together, what's the criteria you will do that? How likely you will start to see those blinded data and help you to make that decision? Great. Yeah. Just to level set, just to reinforce what you said, Roger, what we have said publicly is we expect to be in a position to disclose the PD4, the booster data by the end of the first half of 2027. That will either be concurrently with the PD3 data or there is a scenario under which we would unblind and therefore also disclose the PD3 data prior, which would be about six months plus or minus before then. There is no scenario under which we would unblind the PD3 data and then wait to disclose it. If we are going to unblind it, it is material enough data we would disclose it. For us, there are a few factors at play. Kind of the two most relevant are which just what do we believe is the right communication strategy. Both data sets are required to get a true picture of the total profile of VAX-31. Both data sets are required to put together a package to submit to FDA for an end of phase II meeting. There is the communications component. There is some minor but not material operational component. The other component is we are enrolling in this infant study right now. We will soon be enrolling in a number of adult studies that collectively comprise our VAX-31 adult program. The immunoassay work, the serology work, is conducted by vendors that serve both our adult and infant studies. That will also have an impact in terms of when we would be in a position for not only the adult studies to have the data. You should expect in the early part of next year, not necessarily in January, but the early part of next year, once we're further down the enrollment pathway and have really had a full discussion on the communications to announce what the plan is in terms of the unblinding and resultant disclosure strategy and what the expected timing of those would be depending on where we land. Yeah. We'll stay tuned, right? In terms of strategy, and then you will give us a little bit more guidance. Just curious about how you're going to make that decision. Maybe you will tell us kind of a little bit more specifics later. Okay. Good. That's that. Obviously this is phase II. After this, you will end the phase II, meaning just follow the same kind of playbook as the adult. Move forward. This is a vaccine space and the vaccine play, and then the manufacturing matters a lot. I know you've been building out the manufacturing. Where you are for that, and then what's the CAPVAXIVE right now, and then what you're about to spend a little bit more on the manufacturing part. I'll do it intact in just one. Yeah. We have already made a very fulsome investment on the manufacturing side. We entered into a working relationship with Lonza almost a decade ago, and we will be launching initially out of multipurpose facilities at Lonza, for which we've made many, many batches of the vaccines over the preceding years. We recognize that in those multipurpose facilities, the capacity isn't there to be able to meet the full demand that we could expect for our vaccines. We recognized that a few years ago. We expanded our relationship with Lonza and have invested in a dedicated larger capacity facility that we will bring online shortly after the launch in adults and certainly in time to support the launch in infants, where, as you say, they get four doses. Adults only get a single dose. You see a really major uptick in the demand for doses associated with the infant indication. We've mostly completed that facility construction, and maybe I can hand it to you to talk a little bit about the CAPVAXIVE and a bit more about the details on the manufacturing front. Yeah. We just provided an update a couple of weeks ago in connection with our Q3 results. When we embarked on this initiative to build out this incremental capacity, we guided to completion of this dedicated suite within a Lonza complex in the early part of 2026 at a total cost of $300 million-$350 million. We're on track and on budget. We reaffirmed that just a couple of weeks ago. We are well positioned to get that facility beginning to make product, to qualify that facility, and to build inventory in anticipation of the future launches. I would just add what Lonza does on our behalf for a number of components of the manufacturing, including the drug substance. We have done and will continue to do the drug product, the fill finish in the United States. We're currently working with a very well-regarded CDMO there. As some of you may have seen, we announced several weeks ago our relationship with Thermo Fisher to serve as our long-term fill finish facility. I think the punchline is we are well positioned with both Lonza and this existing U.S.-based CDMO to support the expected demand for the adult indication. These newer facilities, this dedicated suite with Lonza and this relationship with Thermo Fisher, we expect will be on track to meet the supply requirements upon the infant indication coming online, which obviously is significantly larger given you have a global market and a multi-dose market versus the U.S. market, which historically has been principally U.S. that is growing for reasons we talked about. Excellent. Okay. Great. This space historically is mostly large pharma playing this vaccine and the monoclonal vaccine. Now you are one of the biotech, but you still have a lot of the large pharma is doing this. Any updated kind of competitive landscape we should be aware, I think, of either they're pushing forward to 25 and then they're also moving to the 31 and GSK do the same thing. Any updated kind of information you can give us? Yeah. They have been providing periodic updates on their programs. Yeah, I think the most recent update was that Pfizer has pushed back the potential initiation of the phase III program for their 25-Valent program from late this year to potentially late next year. They are still in the process of nailing down what the formulation would look like for that program. I think it is still a bit of a work in progress. We know they have talked about a 30-plus valent program that is in preclinical development, which will be an additive program on top of this 25-Valent. I think it is kind of a first things first kind of moment for them. They are trying to get that 25-Valent on track. GSK also has had a 24-Valent program that they've been working on, but they've fallen back to a 30-plus valent program, I think, to be more competitive and try to match up with us. That program's just gotten the clinic with a small phase one study. They're behind us and we've generated really compelling data to date, but I'm sure they're going to keep trying hard. Excellent. Okay. How's the balance sheet, Andrew? Then how does that support everything we just said? Yeah. Based on our Q3 update, we have $2.7 billion on the balance sheet as of September 30. Really in a strong position, and what we've indicated is that balance sheet is sufficient to fund our operations and advancing our business and, of course, investing in our PCV programs as expected into the middle part of 2028. That would put us to the cusp of the potential launch of the VAX-31 adult program. Obviously a period through which we're able to fund multiple milestones, not only all the phase 3 readouts for the adult VAX-31 program, but as well as these key readouts for the ongoing VAX-31 infant study. Excellent. Thank you. Thank you for being with us. Thank you, everyone. Thank you. Thanks.