Vaxcyte, Inc. (PCVX) Earnings Call Transcript & Summary

Good morning. My name is Olivia, and I'll be your conference operator today. At this time, I would like to welcome everyone to Vaxcyte's VAX-24 Phase I/II Proof-of-Concept Study Results of Conference Call. [Operator Instructions] I would now like to turn the call over to Andrew Guggenheim, President and Chief Financial Officer of Vaxcyte.

Great. Thanks, everyone, and thanks, operator, and good morning, everyone. I'd like to welcome you to Vaxcyte's conference call to discuss top line results from our Phase I/II Proof-of-Concept Study, evaluating the safety, tolerability and immunogenicity of VAX-24, the company's investigational 24-valent pneumococcal conjugate vaccine in healthy adults aged 18 to 64. I'm joined this morning by our Chief Executive Officer, Grant Pickering; and our Chief Operating Officer, Jim Wassil. Early this morning, we issued a news release announcing our top line results and the presentation, we will be reviewing today, will be made available shortly on our website and via an 8-K filing. Copies of this and our other news releases, latest corporate presentation and SEC filings can be found in the Investors & Media section of our website. I'd like to remind you that during this call, we will be making certain forward-looking statements about Vaxcyte, which are subject to various risks and uncertainties. These include, but are not limited to, statements related to the potential benefits of our vaccine candidates, including breadth of coverage and the ability to deliver a potentially best-in-class pneumococcal conjugate vaccine, the process and timing of anticipated future development and manufacture of our vaccine candidates, the achievement of future funding milestones, the growth and expansion of the pneumococcal vaccine market, the market opportunity for our vaccines, our expectations regarding the spectrum of coverage, regulatory pathway, adoption speed and immunogenicity of our vaccine candidates, the timing of the initiation, progress and expected results of our preclinical studies, clinical trials and research and development plans, and other statements that are not historical fact. Any forward-looking statements are based on facts and assumptions as of today, and we undertake no obligation to update them. Our actual results may differ materially from these statements. Investors should read the risk factors set forth in Vaxcyte's Form 10-Q for the quarter ended August 8, 2022, and any subsequent reports filed with the SEC. And with that, I'll now turn the call over to Grant Pickering. Grant?

Great. Thanks, Andrew. On behalf of all of our Vaxcyte colleagues, we are honored to unveil the fantastic results from our clinical POC study today. We believe we have unprecedented results that validate our PCV franchise approach and its ability to deliver broad spectrum PCVs that maintain robust responses relative to lesser spectrum predecessor vaccines. The results support best-in-class potential for VAX-24, met all the objectives of the study and identified the optimal dose for advancement to Phase III. On the safety front, VAX-24 demonstrated a safety and tolerability profile similar to Prevnar 20 for all the doses tested, and on the immunogenicity front, met or exceeded regulatory standard for all 24 serotypes for VAX-24 using the conventional 2.2 microgram dose of polysaccharide without the need to push the dose higher. And drilling down a bit, we met the standard OPA responses on the non-inferiority criteria for all 20 serotypes common with PCV20, of which 16 achieved higher immune responses relative to PCV20 and met the standard superiority criteria for all 4 additional serotypes unique to VAX-24. We also saw, across all the VAX-24 doses studied in this Phase II trial, all of them could have been eligible to advance. But the 2.2 microgram dose was optimal and didn't require a dose boost, which is what we were investigating with our 2.2, 4.4 mixed dose cohort, where we selected 7 strategically important strains where non-inferiority was more of a necessity and yet we achieved without having to push the dose. We believe, these data validate our platform and the carrier-sparing PCB franchise that we've been hard at work developing to increase spectrum of coverage and maintain robust immune responses, which we will further highlight today as we provide guidance on our life-cycle management strategy, unveiling the composition of our 31 valid VAX-XP program and timing for its IND. But for today, VAX-24 is the star of the show as we will be advancing to pursue breakthrough therapy designation to rapidly advance the VAX-24 program. We will be looking for the receipt of the Phase II study that's already fully enrolled in the adult 65 and over, followed by the end of Phase II meeting with FDA to seek agreement on the Phase III pivotal non-inferiority study using a similar design as the Phase II POC study results you'll see shortly. We will also be initiating our pediatric development program for VAX-24 within infant IND submission and Phase II study initiation expected in the first half of 2023. Our mission at Vaxcyte is to protect humankind from the consequences of bacterial disease and the global impact of pneumococcal disease remains significant, particularly given the circulating disease driven by serotypes outside of current PCVs. Thus, the spectrum of coverage drives adoption in this PCV segment, which inspired the VAX-24 profile with 2 key objectives in mind: to provide broadest coverage of any PCV, including an incremental 10% to 15% coverage in adults over the current standard of care PCV20, and VAX-24 provides the benefits of a conjugate vaccine, while fully eclipsing the coverage of Pneumovax 23, so as to negate the need for this non-conjugate type of vaccine given the huge benefits of the T cell-dependent boostable responses confer and have only been shown with conjugate vaccines. As you'll see in a moment, we believe our carrier-sparing approach, underpinning our PCV franchise has been validated by our POC study results today, and serve as a triumph of rational drug design that overcome the limitations of conventional conjugation chemistry that can mask the on-target T cell epitopes on the protein carrier, resulting in carrier suppression, and lower overall immune responses when coverage has been expanded. This has been a remarkably consistent finding with conventional PCVs. And at that site, we had developed our carrier-sparing conjugate vaccines that sites specifically attach the conventional antigens and conventional protein carriers to overcome carrier suppression by enabling consistent exposure of the T cell epitopes that avoid the off-target effects from protein carriers that compete for the CD4 help that enables us to use less protein carrier per conjugate without sacrificing immunogenicity. This is the thesis that enables broader spectrum, carrier-sparing conjugate vaccines using our platform. The pneumococcal vaccine market is poised for significant growth, particularly in the adult market. This is inclusive of multiple factors that VAX-24 is poised to capitalize upon, including strong ACIP consideration to expand the U.S. universal recommendation from 65 and up, to 50 and up adults, and would necessitate prime-boost for effective long-term protection, which has been limited by continued availability of Pneumovax 23, for which VAX-24 could obviate any rationale for continued use upon its introduction. And just this past Friday, the ACIP voted to support PCV20 catch-up for adults who previously received PCV13 and Pneumovax 23 due to the benefits of its broader spectrum coverage that VAX-24 would meaningfully surpass. Thus, the opportunity is vast, and our responsibility is high, which has fueled our patient approach to ensure we can produce -- and to produce this important vaccine at the quantities and quality to meet future demand. And now allow me to hand the baton to Jim to unveil our Phase I/II results, which we believe puts us on the path to delivering the best-in-class PCV.

Thanks, Grant. So I'll start with slide design that's on Slide 9. This is a randomized observer-blind dose finding controlled study to evaluate the safety, tolerability and immunogenicity of VAX-24 versus the standard of care, which is PCV20 in adults aged 18 to 64. The Phase I enrolled 64 healthy adults aged 18 to 49, and they were randomized equally to VAX-24's low, middle and mixed doses as well as PCV20. Safety data were reviewed with an independent data monitoring committee before proceeding to the clinical proof-of-concept study, which enrolled 771 adults aged 50 to 64 years of age, who are also randomly assigned to the same dose groups. Safety follow-up in immunogenicity 1 month after dosing are available in this report. One to 6 months of unsolicited adverse events follow-up is ongoing for the Phase II. Group unblinded safety immunogenicity data is presented. Slide 10, PCV20 here is composed of 2.2 micrograms per polysaccharide with the exception of 6B, which has 4.4 micrograms. You can see for VAX-24, the low dose has 1.1 micrograms of polysaccharide for all 24 groups -- sorry, serotypes included in the vaccine. The VAX-24 middle dose has 2.2 micrograms per polysaccharide for all 24 serotypes including. And now you can see for VAX-24, the mixed dose, what we did was we had a mix of 2.2 micrograms of polysaccharide for all serotypes, with the exception of 7 serotypes, those being 3, 6B, 7F, 9B, 18C, 19A and 19F, which were all included in the vaccine at 4.4 micrograms. These stereotypes were strategically chosen based on their epidemiological relevance that they were more prevalent or circulating in the environment, or that they had previously demonstrated a dose-dependent immune response. So this dose was included to increase the probability of generating non-inferior immune responses for those key serotypes. Slide 11. Safety, tolerability and immunogenicity outcome measures included -- safety, tolerability and immune outcome measures include safety and tolerability assessments at day 7, 29 and 180 days for Phase I and II portions of the study. Day 7 assessment included solicited local and systemic reactions. Assessment of unsolicited adverse events occurred through day 29, an assessment of serious adverse events, including new onset of chronic illnesses and medically attended AEs occurred through day 180. Immunogenicity assessments occur only in the Phase II, 50 to 64 age group, and included opsonophagocytic assay, geometric mean titers, or GMCs, IgG geometric mean concentrations, percent of subjects achieving a fourfold rise in OPA, geometric mean ratios for the serotype-specific opsonophagocytic activity assay. In the Phase I study, 64 subjects were vaccinated with excellent follow-up. 3 subjects discontinued, 59 subjects completed 6-month follow-up and 2 subjects are ongoing. In the Phase II study, we enrolled 771 participants, all of whom were included in the day 29 safety assessment, and 90% of whom were included in the immunogenicity assessment. Slide 14. You can see here, the demographics of the Phase II cohort for the 50- to 64-year-olds, and they are generally balanced across cohorts and similar for the safety and immunogenicity population. Median age was 57 years old and 60% to 70% were female, and it included the inclusion of 15% to 20% Black or African Americans, and the BMI was roughly 29%. Slide 16. Local solicited adverse events for the 50- to 64-year-olds are presented on this slide, and they demonstrate less than 10% of participants reported redness and swelling at the injection site, while 70% to 80% of participants reported pain at the injection site. Importantly, these events were similar across the VAX-24 study groups as well as to the comparator PCV20. The majority of solicited local adverse events were mild to moderate in severity, resolving within 24 to 48 hours after vaccination. Slide 17. Solicited systemic AEs and stage group demonstrated a low proportion of participants reporting fever, approximately 20% reporting arthralgia, 30% headache, approximately 40% fatigue and around 50% to 60% reporting muscle pain. Similar to the local adverse events, these systemic events were similar across VAX-24 study groups as well as to the PCV20 Group. The majority of these solicited systemic AEs were mild to moderate in severity and also resolved within 24 to 48 hours after vaccination. Here on Slide 18, you can see the safety profile in the age cohort of a 50- to 64-year-olds, and also is considered similar across all study groups, including PCV20. No participants reported serious adverse events deemed by the clinical investigator to be related to the vaccine. Furthermore, there were no new onset chronic conditions deemed related to the vaccine nor any deaths reported in the study. Roughly 11% to 15% of participants had any treatment AE, while 1% to 3% of participants reported a serious AE or new onset chronic illness, again, similar across all study groups. There were no safety concerns in either the Phase I or Phase II portion of the study, and the Phase I portion of the study, while not shown here, had similar patterns of safety and reactogenicity outcomes. I'd now like to go to the top line immunogenicity results. On Page 20. Now, before discussing the immunogenicity results from the Phase II study data, I'd first like to just review what is considered the standard regulatory criteria for evaluating pneumococcal conjugate vaccines. For the 20 serotypes in common with PCV20, the historical regulatory non-inferiority criteria is that the lower bound of the 95% confidence interval of the OPA geometric mean titer ratio has to be greater than 0.5. While to demonstrate superiority, the lower bound of the 2-sided 95% confidence interval of the OPA geometric mean titer ratio needs to be greater than 1.2 and the lower bound of the 2-sided 95% confidence interval of the difference in the proportion of participants needed to show a greater than or equal to fourfold increase in titers is greater than 0. For the incremental serotypes, those that are in VAX-24, but not in PCV20, the lower bound of the 95% confidence interval of the difference in participants with a greater than or equal to fourfold rise in OPA titers needs to be greater than 10%, and the lower bound of the 95% confidence interval of the OPA geometric mean titer ratio needs to be greater than 2.0. With that, I'd like to now discuss the immunogenicity results. As you can see here on Slide 21, what we're showing is the dose that we've decided to advance into the Phase III clinical studies. And I just want to orient you as to what you're seeing here. So on the left, what you see is a forest plot, and I just discussed the regulatory non-inferiority requirement. Well, on this plot, anything at 0.5 or below, actually would miss on the non-inferiority requirement. So in terms of overall responses, at 1.0, what we're doing is, we're comparing the responses of VAX-24 to PCV20. A response of 1 would mean that you had an equivalent response of VAX-24 compared to PCV20 for your OPA titers. So the ideal would be to have as many of these results to the right of the line on this graph past the 1.0. And as you see this, that 16 out of the 20 serotypes are actually better than 1.0, meaning that they had responses with OPA titers higher than PCV20. And you can see on that graph 4, in fact, reached the typical significance for superiority. So overall, we can see that we met the non-inferiority requirement. And for the majority, they were higher, with 4 being statistically superior. On the right side, what you see are the 4 incremental serotypes, and the regulatory requirement here is that you need to see a significant increase in the fourfold rise in antibody titers. And for all 4 of these, we met the requirement of being greater than or equal to 10% for the lower bound of the 95% confidence interval. You'll note for 17F that the responses for the fourfold rise were a little bit lower. The overall response is stemming up were very robust. The OPA titers were similar to all the other serotypes that were tested. However, in this study, 17F had higher rates of pre-titers, which influenced the overall increase in the fourfold rise titers. But as you can see, huge safety margin for Phase III to be able to meet the non-inferiority requirements for licensure. The next slide. So what we're seeing here now is the overall results of all 3 doses that were tested in the study. On the left side, you can see the forest plot for 1.1 microgram dose. The conventional dose that is used by PCVs right now is 2.2 micrograms. So this represents half the antigen. And overall, this has very, very good results and that we could move these results forward into Phase III. However, when we looked at the 1.1 versus the 2.2, the 2.2 had much higher immunogenicity. We felt optimizing immunogenicity going forward was the overall strategic goal and decided to advance the 2.2 microgram dose into the clinic. For the mix dose, I had already said, the intent of the mixed dose was to ensure that we did not miss on very important epidemiologically relevant serotypes. And for those serotypes with -- marked with an X, you can see, those were the ones that were dosed at 4.4 micrograms. All of those had a dose-dependent response and actually had a better response than 2.2 micrograms. But fortunately, in the 2.2 microgram, we had very good responses as well. So we didn't need to go as high as the 4.4. You also see with the mixed dose, we did see a diminution in some of the serotypes that were dosed at 2.2 micrograms. This was very much expected. The reason being that as you add more carrier protein, we would expect to have some degree of immunological interference. This dose is very helpful to allow us to optimize our study design for our next-generation candidate XP. So the information gained from this information will allow us to ensure optimal design and path forward for our second-generation product. Next slide. And ultimately, here, you can see that you do see a dose-dependent immune response overall for all the 7 serotypes that were contained, the 1.1, 2.2 and 4.4 microgram dose. So this does support our premise that in cases where we need to, we can actually increase the dose and improve the immune response. So the 4.4 microgram, though was not deemed necessary because the 2.2 microgram dose demonstrated high OPAs for all of the 7 serotypes tested versus PCV20. Slide 22. So what you see here, all 3 doses -- sorry Slide 24. So here, we see overall the OPA geometric mean titers for the -- all 24 serotypes. And this data reinforces what we have been showing on previous slides. As you can see, based on the OPA geometric mean titers, there were robust immune responses demonstrated across all 24 serotypes. Slide 25. We also measured IgG responses in this study, and this shows the IgG geometric mean concentrations, which are the binding antibodies. While regulatory approval is not based on the IgG, it's rather based on the OPA geometric mean titer ratios, it is important to note that the IgG geometric mean concentrations are generally consistent with the functional OPA immune responses shown across the 24 serotypes, with similar trends that reinforces the overall robustness of the performance of VAX-24. So in summary, I want to say that these study results in the 50- to 64-year-old adult cohort supports the potential for a best-in-class pneumococcal conjugate vaccine. VAX-24 demonstrated a safety and tolerability profile similar to PCV20 at all doses amongst the 50- to 64-year-old cohort and met or exceeded the regulatory standard for all VAX-24 serotypes at the conventional 2.2 microgram dose, which is the dose we plan to advance into Phase III. We also met the standard OPA response non-inferior criteria for all 20 serotypes common with PCV20, of which 16 achieved higher immune responses, and they exceeded the standard superior criteria for all 4 additional serotypes unique to VAX-24. Furthermore, the learnings from the study, inclusive of VAX-24 mixed dose have served to inform the optimal design for VAX-XP clinical program, given our ability to add additional serotypes without sacrificing overall immune responses. And so with that, I'd like to turn it back over to Grant for some closing remarks before we open up the line for Q&A. Grant?

Excellent. Thanks, Jim. Yes. It's really quiet a moment. I mean this is the kind of data that we've dreamt of, and we've had untold conversations with everyone that's interested in the story about how many strains can we miss on. And the precedent has shown, you can miss on multiple strains when you're adding incremental coverage, and lo and behold, we hit on all of them and have been able to show that the incremental strains are already also showing the sort of responses that would give us the confidence that, that spectrum of coverage is going to be increased. So really an incredible moment for the company, and I'm thrilled to be able to report these results to you all today. But looking ahead, and I'll call out the slides now, Slide 28, this is the regulatory pathway. We get the benefit of an already very clear set of parameters that have been established from a precedent perspective for pneumococcal conjugate vaccines. These surrogate immune endpoints have been well established in both adult and infant market. In adults, it's the OPA responses that Jim just got done reviewing. And in infants, it's the IgG responses that were, of course, very encouraging here in this adult study that will put us in a position to have an opportunity to gain a full approval with the right data based on those validated surrogate immune endpoints without requirement for field efficacy studies given the correlation historically between those responses and protection. So these are the data that we would expect to need to generate from a pivotal Phase III perspective in order to get this program on track for a BLA filing. And the whole non-inferior immune response standard is really something that has been the norm by virtue of the incremental coverage that pulls these broader pneumococcal conjugate vaccines through. And we've had to tolerate lower responses, i.e., non-inferior responses as the bar for the common serotypes with the lesser valent strains. But here, again, what we're seeing with this VAX-24 data is that we're avoiding that historical trade-off, which is what's so exciting about the data we've just shared with you. There's also remarkable consistency across Phase II POC and eventual Phase III pivotal study results in both, the adult and infant programs, which is one of the reasons why we're so enthusiastic about this first clinical study readout for VAX-24. On Slide 29, just looking forward to the VAX-24 program, we have quite a number of important key milestones that are going to be reading out over the next few years. In the adult program, we'll be in receipt of the Phase II study results for the adult 65 and up. We'll have that data in the first half of 2023. As it relates to the final results of today's study, we'll have those safety data also in the first half of 2023. And the combination of those 2 results will put us in a position to proceed with meetings with the FDA in order to inform on the Phase III program. We anticipate having that clarity in second half of 2023 to put us in a position to initiate the Phase III pivotal clinical study program for which we would expect to receive the top line data in 2025. As we all know, the pediatric program is of crucial importance in this space. As I said at the outset, we'll be expecting to file the IND for VAX-24 for infants and initiating a Phase II study in the first half of 2023 as well. And we would be in a position to get the top line data receipt after the primary series, which is after the first 3 doses in infants in 2025, and that would then be followed by the Boost data that would come in 2026 post dose 4. And with that, last but not least, we want to provide guidance on our VAX-XP program. We view VAX-24 as a best-in-class PCV in both, adults and infants, but with the inevitability of serotype replacement over time, VAX-XP has a category killer profile, for which we have been hard at work manufacturing this past year. And if we move on to Slide 31, we're going to do the big reveal on timing and composition of VAX-XP. But what you can see is there's an opportunity with this profile to increase the coverage all the way to around 95% of circulating strains. We will be advancing a 31 valent carrier sparing PCV. We will be expecting to file that IND submission in the second half of 2023 and would be expecting to have receipt of top line data in adults in 2024. And on the next slide, what we believe we have is VAX-24 and VAX-XP having the potential for sustained leadership in this growing pneumococcal vaccine market. And if you look at the coverage, for VAX-XP, these 7 strains that we identify here represent an incremental 25% coverage on top of what we expect to obtain with VAX-24 in the adult population, while maintaining coverage of the original serotypes to ensure that they don't rebound. It's been an audacious mission from the beginning, but we were inspired by today's news, and we will transition into the Q&A portion of today's call. Operator?

[Operator Instructions] Our first question is coming from the line of Roger Song with Jefferies.

Great. Congrats for this fantastic results. Maybe just 2 from us. One is the -- given the active comparator Prevnar 20, how do you see the Prevnar 20 performance compared to their past kind of study without or the real-world kind of data? and specifically, Prevnar 20 seems has less immunogenicity compared to Prevnar 13? And how do you see VAX-24 during this immunogenicity back compared to Prevnar 13? I do have another follow-up.

Yes. Thank you, Roger. I'm going to have Jim answer that question.

Sure. So Roger, in terms of comparisons with other studies, in particular, this assay that we used for functional antibody responses, it is somewhat difficult to compare across these studies. So I'll give you that as a cautionary note. But that said, we did look at these responses relative to other studies that have PCV20 in them. And we saw comparable results within the range of variability of the assay. So we didn't see anything untoward in that study. In terms of the -- how we read the overall results, you are absolutely right that PCV20, overall, had lower immune responses than PCV13. If you look at the results of our 2.2 dose that we've decided to move forward in the Phase III clinical study, you can see 16 of the 20 of our results were actually higher than PCV20, some much higher in terms of 17%, 20% and even 40% to 50% range. And so in many ways, we think that we have sort of reinstated the similar immunogenicity overall that you had seen it with PCV13 with our conventional dose that we plan on moving forward.

Yes. And if you go back, and you were to average the drop for the common 13 strains across Prevnar 13 and Prevnar 20, you'd see that there was an average drop of 15% in the titers. And what we saw with the comparison for VAX-24 across the 20 common serotypes with Prevnar 20 was an average increase of 20%. So as Jim said, we're really restoring the sort of magnitude of responses that we've seen historically with a 13 valent pneumococcal conjugate vaccine, but with a spectrum of a 24 valent pneumococcal conjugate vaccine. So it's very encouraging.

Excellent. Thanks for the color and the comments. And maybe just a quick follow-up on this is the -- it's very encouraging to see you are moving forward VAX-XP as well that's going to cover 95% of the pneumococcal disease. Given the learning from this mixed dose in Phase II, and can you just elaborate on how you're going to optimize the VAX-XP, and in order to make sure you broaden the coverage while still maintaining this immunogenicity?

Yes. We're still digesting this data that we just opened the data card yesterday. But, yes, Roger, we have gotten a lot of learnings out of these 3 different dose cohorts. I mean I think the working assumption is that the 2.2 microgram dose has worked quite fantastically across all 24 of the conjugates in VAX-24. But we'll certainly take a hard look at VAX-XP and consider whether or not there is a case to be made to look at sprucing any particular strains of relevance. But for the moment, I think the working assumption is, it will be 2.2 across the board. But we'll still have some time to make that call.

[Operator Instructions] Our next question come coming from the line of Umer Raffat with Evercore ISI.

I finally figured out how to raise my hand on this call. I have 2 here, if I may. And first of all, congratulations on the data. I realized 2.2 is the dose of choice heading into Phase III. But I think it's also very clear that there is a dose response there. And I wonder, how much is the max dose per antigen you could pack on the same amount of carrier protein that was used in the 2.2 arm? Could you make a 2.5, for example? And I say that because your odds of, A, certainly locking in non-inferiority on all serotypes on the infants, but then, B, also possibly tracking statistically better in some adult indications could actually go up materially. And I'm curious how you're thinking about that? And then secondly, on safety, you guys tracked Prevnar 20 like. And I remember Affinivax had higher diarrhea, myalgia, fatigue, et cetera, versus Prevnar 13. Can we read into those cross-chart comparisons?

Yes. I think you brought up 2 important points. I think what we're seeing is here that what we believed all along is that we have a more precision orientation with our chemistry approach and seeing this sort of fidelity across the 3 doses is really encouraging. And as you say, there's nothing that forces us to use 4.4. We could consider, as you say, a 3.3 or a 2.8. We've got very good control over drug product and the amount of material added on an individual conjugate basis. So yes, we'll take all the learnings from. [Audio Gap] this and ensure that for all the right strains for which they're defined by their circulation to ensure that we provide the best protection we can with VAX-XP. And as it relates to alternative approaches; outside of conventional pneumococcal conjugate vaccines, yes, this affinity bound approach that was advanced from Affinivax, that's now in the hands of GSK, I think, objectively, we can see -- say that from an immunogenicity perspective, in the same age group, we see substantially better immune responses that are comparable to the current standard of care. I think we see a safety profile that's decidedly consistent in this study with the standard of care, and we are leveraging an approach that's tried and true, leveraging a protein carrier that has reliably shown boostable immune responses, which gives us a great deal of confidence that as the adult market graduates from a single dose to a prime boost, this technology will rise to that occasion and will likewise have the same opportunity in infants. Whereas with novel approaches, the jury is entirely out as to whether or not those approaches will actually be boostable.

But just so I am clear, I think I heard you say you are open to playing with the doses and checking out different doses in the XP construct. I guess my question was on the 24 construct especially as we head into infant. Would you be looking into trying different doses?

So in infants, we do have a dose-ranging study planned as well to ensure that we have the optimal vaccine formulation moving forward, and we can optimize immunogenicity. As Grant said, these are early days. We've got a lot of data here from the adults that we're going to analyze, and we do have the capability of customizing the dose. We'll take the learnings from this and bring it to the infant study as well, as Grant said, for XP, too.

[Operator Instructions] Next question coming from the line of Jason Gerberry with Bank of America.