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Good morning, and welcome to VACCITE's conference call to discuss the Opus 1, Phase 3, Topline Results. Following the prepared remarks, we will open the call for questions. If you would like to ask a question at that time, please press star 1 on your telephone keypad. I will now turn the call over to Andrew Guggenheim, President and Chief Financial Officer of VACSITE. Please go ahead. Andrew Gugenheim, VAC CITE, Thank you, Operator, and good morning, everyone. Welcome to BACSite's conference call to discuss top-line results from Opus 1, our pivotal Phase 3 trial evaluating BACs31 in adults aged 18 and older. BAC31 is our investigational 31-valent pneumococcal conjugate vaccine, or PCV, designed to prevent invasive pneumocockle disease, or IPD, and pneumocochle pneumonia. I am joined today by Grant Pickering, our Chief Executive Officer and co-founder, Jim Walsall, our Chief Scientific Officer and Chief Operating Officer, Luis Hodar, our Chief Medical Officer, and Mike Millett, our chief commercial officer. Earlier this morning, we issued a press release announcing these results. Copies of this and our other press releases, latest corporate presentation, and SEP filings can be found in the Investors in Media section of our website. Before we begin, as noted on slide 3, I'd to remind you that during this call, we'll be making certain forward-looking statements about factsites which are subject to various risks, uncertainties, and other factors that could cause actual results to differ materially from those referred to in any forward- looking statements. For discussion of the risks and uncertainties associated with these statements, please see our press release issued today, as well as our most recent filings with the SEC, including a risk factor set forth in our Form 10-Q for the quarter ended June 30, 2026, and any subsequent reports filed with the SEC. With that, I'll turn the call over to Grant. Thank you, Andrew, and we appreciate you all joining us today. On behalf of the entire VACC site team, I am immensely proud to share that Opus 1 met all pre-specified primary immunogenicity endpoints across all ages studied. Vax31 was also well-tolerated and demonstrated a safety profile similar to the licensed comparators in the study, Capvaxiv, or PCV21, and Prevnar20, or PCB20. These results represent what we believe to be clear validation of Vax 31's potential to substantially broaden disease coverage while maintaining robust immune responses. They further support the potential of our site-specific carrier sparing platform to deliver broader spectrum PCBs that address currently circulating disease-causing serotypes while maintaining pressure on historically prevalent serotypes. Today, we are presenting top-line results. We will present the full data in a peer-reviewed scientific setting, and the complete Opus 1 data set will serve as the cornerstone of our planned VLA alongside Opus 2 and Opus 3 results and a manufacturing consistency study. I'll begin with the opportunity we see for VAX 31, the framework used to evaluate success in Opus 1 and the top-line results. Jim will review disposition, demographics, tolerability, and safety, followed by Luis with the immunogenicity results. I'll return with our next steps and closing remarks before we open the call to questions. Turning to slide six, the pneumococcal vaccine class remains one of the largest and most durable segments of the vaccine market, with combined global sales of approximately $8.5 billion in 2025. Despite current vaccination efforts, the disease continues to be a major driver of global morbidity and mortality, and broader-spectrum vaccines are needed. While the infant segment currently represents the majority of revenues, the adult population is expected to be the primary driver of growth, with the combined market projected to reach $12 billion by 2030. To put the opportunity for Vax31 in context, I'd like to spend a few moments to orient you all as to how the category has evolved and the present tradeoffs we have an opportunity to overcome with Vax31 in order to prevent a substantial residual disease burden. Turning to slide seven, the success of pediatric PCBs reshaped pneumococcal disease 25 years ago. These vaccines protected children and reduced carriage and transmission, providing substantial indirect protection to adults. As vaccine-covered serotypes declined, other serotypes filled that void. This serotype replacement phenomenon drove the development of progressively broader vaccines, including PCV15 and PCV20, that retained the earlier serotypes while adding new ones. But broader coverage has historically come with lower immune responses. This was evidenced with PCV 20 compared with PCv13 in adults, where the responses for all but one of the overlapping 13 serotypes were numerically lower with PCV20 despite meeting non-inferiority for those shared serotypes. With substantial circulating disease over and above PCV 20 coverage, the challenge has been to expand coverage while maintaining the magnitude of immune responses. PCV21 took a different approach to expand coverage, focusing specifically on the serotypes causing adult disease today. It added eight serotypes not included in PCB20 while leaving out nine of the historically important serotypes retained in PCB 20. That approach increased the coverage of currently circulating adult disease but forced healthcare providers to make a choice between two vaccines each of which has meaningful coverage gaps. Now with the resurgence of serotype 4 from very low levels following pediatric vaccination, it is now one of the fastest growing serotypes in western states and in Europe. Likewise, serotype 19F also continues to persist and requires continued inclusion to prevent further resurgence. Both are included in PCB20 but absent from PCB21. This has resulted in a difficult trade-off for healthcare providers as they choose between two equally recommended vaccines with partially overlapping coverage and at present the market is split with a slight edge to PCV20. Vax31 was designed to overcome these trade-offs by retaining all of the PCV 20 serotypes adding serotypes responsible for adult disease that are covered by PCV21 and expanding coverage even further. That required the incorporation of 31 serotypes into a single vaccine and demonstrating that immune responses can remain robust. Our site-specific conjugation and carrier-sparing technology is designed to rise to the challenge. And as you can see on this epidemiology slide 7, BACS31 incorporates serotypes responsible for 95% of invasive pneumococcal disease and 88% of pneumococal pneumonia in U.S. adults 50 and older, a greater proportion than either PCB20 or PCV21. The strength and consistency of our Phase 2 data gave us confidence that we could broaden coverage without sacrificing immunogenicity. That gave us the conviction to take on the more stringent non-inferiority standard in our Phase 3 study. With that backdrop, let's review the approval standard for immunogenicities and the pre-specified framework used to evaluate Vax31 head-to-head with PCV20 and PCV21 in Opus 1. Turning to slide 8, this slide puts the immune response standards in context. Opsidophagycytic activity, or OPA, is a functional measure of how well vaccine-induced antibodies help immune cells kill pneumococcus. Because there is no established antibody threshold that reliably predicts protection in adults, we compare these responses with those of licensed vaccines. For each serotype, we measure the OPA geometric mean titer, or GMT, after Vax31 and after the licensed comparator, and calculate a ratio between the two, which is the geometric mean ratio, or GMR. The dots in this slide illustrate the point estimates of the GMR, so VAX 31 divided by the comparator, and the horizontal lines show the two-sided 95% confidence intervals. The left end of each line is the lower bound of that confidence interval, which we'll use as shorthand LBCI going forward. The pivotal PCV20 and PCV21 trials required their lower bound to be greater than 0.5. Given the concern that repeated bridging would lead to progressively lower immune responses, we aligned with the FDA to inaugurate a more stringent threshold of the LBCI greater than zero point 667 in Opus 1. In this slide, moving from left to right, the shaded blue area represents the historical threshold of 0.5. The gray area represents the higher Opus 1 threshold of 0.667, approximately two-thirds of the comparator response rather than one-half. Farther to the right, the green area represents a lower bound greater than one, which indicates statistically greater immune responses. And finally, the purple area represents the primary superiority assessments involving the three unique serotypes and cross-reactive 20B, where the lower bound must exceed 2.0. We believe meeting the higher non-inferiority standard with a broader spectrum vaccine will set a new bar for future adult PCB development. Turning to slide nine, let's review what Vax31 needed to deliver to meet the study's primary endpoints. Opus 1 was a complex study with two comparatives, partially overlapping serotype coverage, and two different age groups. So let's break it down. It begins with the four co-primary immunogenicity endpoint groups in adults 50 and older. The first group contains the 11 serotypes shared by all three vaccines, where Vax31 was compared with both PCV20 and PCV21. For each serotype, the primary criterion and required non-inferiority to one or both comparators via the OPA GMRs, requiring the lower bound to exceed 0.667, inclusive of a pre-specified alpha penalty on a serotype by serotype basis in the protocol to account for the two comparisons. For the second group, the nine serotypes unique to VAX31 and PCV20 were compared to establish the OPA GMRs with the primary criterion for non-inferiority requiring lower bound to exceed 0.667. For the third group, the eight serotypes unique to VAX31 and PCB21 were compared using the same non-interiority criterion. Together, these three groups account for all 28 shared serotypes evaluated for non-inferiority. The fourth group assessed superiority for the three serotypes unique to VAX31, along with cross-reactive serotype 20B. These assessments used a superiority margin of 2.0 for the OPA geometric mean ratio, with success required against one or both comparators, inclusive of a serotype-by-serotype pre-specified alpha penalty in the protocol to account for the two comparisons. Overall co-primary success in the trial required all of these 32 assessments to succeed, all 28 non-inferiority assessments, and all four superiority assessments. If all 32 assessments were successful, we could then proceed to the formal primary immunobridging analysis, comparing Vax31 responses in adults aged 18 to 49 versus those aged 50 to 64. All 32 comparisons, including the 31 vaccine serotypes and cross-reactive 20B, also had to meet the same non-inferiority criterion using the 0.667 margin. Safety and tolerability were also evaluated as a primary objective in each age cohort. Separately, we will show the pre-specified individual non-inferiority comparisons with PCV20 and PCV21 for the serotypes shared with VAX31. With that comprehensive setup, as reflected on slide 10, we are thrilled to report that VAX 31 met all 32 pre-specific co-primary immunogenicity assessments, inclusive of all 28 non-inferiority assessments and all four superiority assessments. It was a clean sweep of the pre-specified co-primary endpoints, an outcome that exceeded our expectations. That success continued with in vitro bridging. All 32 comparisons across the age groups also met non-infériority. Importantly, VAX 31 was well-tolerated with a safety profile similar to the comparators. The individual comparator results, which we know many of you were closely watching, also surpassed our expectations. For the 20 overlapping serotypes with PCV20, we went 20 for 20 on OPA-GMR non-inferiority with lower 95% confidence bounds greater than 0.667. For the 19 overlapping serotypes with PCV21, VAX31 went 17 of 19. For serotypes 3 and 12F, the lower 95% confidence bounds did not exceed 0.667 versus PCV 21, but both exceeded the historical 0.5 threshold. That historical threshold was pre-specified as a secondary endpoint in the study, and as a reminder, was the standard used in the pivotal PCV20 and PCV21 trials. The complete data set and remaining studies will be subject to FDA review. However, based on regulatory precedent, we believe these results support an approvable profile. With the potential to combine broader disease coverage and robust immune responses in a single 31 valent vaccine if approved we see the potential for a blockbuster commercial opportunity for vax 31 in the growing adult market with that i will turn it over to jim to take you through the next section of the presentation thanks grant i'm extremely pleased to be able to share the results of the opus one study with you today in terms of the trial design as seen on slide 13 opus 1 is a randomized, double-blind, active-controlled Phase III trial that vaccinated 4,047 adults in the United States, 3,572 aged 50 and older, and 475 aged 18 to 49. As shown here, adults 15 and older were randomized equally to receive either Vax31, PCV20, or PCV21. Adults aged 18-49 were randomized 3 to 1 to receive either the Vax31 or PCV20 arms, respectively, with PCV-20 serving as the safety comparator in that younger cohort. The primary OPA comparison was assessed one month after vaccination. Solicited reactions were collected for seven days and unsolicited adverse events through one month. One month after vaccination, medically attended adverse events, nuance of chronic illness, and serious adverse events were followed through six months. Starting briefly to the study disposition, slide 14, Opus 1 was well executed with high participant retention and nearly complete safety and immunogenicity follow-up across both age cohorts. In adults 50 and older, at least 96% of vaccinated participants were included in the immunogenicities of valuable population across three treatment groups. We saw similarly high follow-ups in adults 18 to 49 with approximately 98% of BAC 31 contributing invaluable immunogenicity data. Overall, these high retention rates provide a robust data set for the pre-specified safety and immunogenicities analyses. Turning to slide 15, in terms of demographics, approximately two-thirds of participants were between 50 and 64 years of age, and about one-third were 65 or older, with comparable distributions of sex, race, ethnicity, and body mass indexed across BACS31, PCV21, and PCV20, with substantial diversity amongst enrolled participants. Importantly, more than a quarter of subjects enrolled had one or more at-risk conditions for pneumococcal disease. Overall, there were no meaningful baseline imbalances that would be expected to affect interpretation of the comparative safety or immunogenicity results. In adults 18 to 49, as you can see on slide 16, baseline characteristics were generally similar between the randomized VAC31 and PCV20 safety groups. For the immunobridging analysis, the relevant comparison is between VAC31 recipients aged 18 to 49 and VAC 31 recipients aged 50 to 64. Because those two age groups were not randomized against each other, expected baseline differences existed. The pre-specified immunobidging model therefore adjusts for baseline open titers and the pneumococcal disease risk status rather than relying on raw group needs. On slide 18, we are looking at local and systemic solicited reactions in adults 50 and older. Let me orient you to the slide. The green columns represent BAC31, the blue columns PCV20, and the gray columns PCv21. More severe reactions are represented by darker colors. BAC 31 was generally well-tolerated. Solicited reactions were predominantly mild to moderate and transient, with the majority resolving within 48 hours. reactogenicity was broadly consistent with the licensed comparators, although some reactions, particularly injection site pain and muscle pain, were somewhat more frequent with BACS31. We see the same overall profile in younger adults here on slide 19. Reactogenicity with similar to PCB20, predominantly mild to moderate and transient, with the expected local and systemic symptoms. Moving beyond solicited reactogenicities monitoring, slide 20 summarizes the broader safety experience across both adult age cohorts. Unsolicited adverse events were collected through one month, while medically attended adverse events, new onset of chronic illnesses, and serious adverse events, were followed through six months. The broader safety profile was reassuring and generally balanced across groups with no apparent pattern suggesting a safety signal. No serious adverse events were considered vaccine-related, and there were no study discontinuations due to adverse events. Four deaths occurred in the older cohort, two in the Vax31 group, and two in PCC21 group, and all were assessed as unrelated to vaccination. With that, I'll turn the call over to Luis to review the immunogenicity results. Luis? Thank you, Jim. Let's now turn to the immunogenicity results, starting with the four pre-specified primary immunogenicities groups Grant outlined earlier. The first plots on the next few slides show OPA geometric mean ratios, or GMRs, under 95% confidence interval. And for the primary analysis involving two licensed competitors, we also apply the pre-specified Hopper adjustment for multiplicity. For the first endpoint group, the 11 serotypes contained in all three vaccines, the pre-specified statistical analysis plan required Vax31 to demonstrate non-inferiority against at least one licensed competitor for each serotype, using the multiplicity adjustment we just described. As reflected on slide 22, VAX31 met that criterion for all 11 of 11 pseudotypes. The blue points show the comparisons with PCB20, and the gray points the comparisons with PCB21. For pseudotype 3 and 12F, the PCB21 comparison did not meet the more stringent 0.667 threshold, their PCB20 comparisons met the higher 0.667 non-inferiority criterion with the pre-specified HOPPR adjustment. Therefore, both serotypes met the pre specified primary criterion. I will address these serotypes with respect to the individual comparisons compared to PCB20 and PCB21 on a later slide. For the second and third endpoint groups, the nine serotypes shared only with PCB20 and the eight shared only with PCB21, the comparison is simpler because each serotype is contained in only one of the two license comparators. On the left side of slide 23, Vax31 met the pre-specified non-inferiority criterion for all 9 of 9 serotypes shared with PCB20. On the right, it met the criterion for 8 of 8 serotypes share with PCB21. Importantly, 31 of these 17 comparisons clear the more stringent 0.667 non-inferiority margin. Together with the 11 serotypes on the previous slide, PAX 31, therefore, met the pre-specified non- inferiority criterion across all 28 serotypes shared with the licensed competitors. According to slide 24, the fourth endpoint group includes the three serotypes unique to PAX31, 2, 7C, and 20C, together with the cross-reactive assessment of 20B. For this group, the statistical bar was higher. The lower bound of the 95% confidence interval for the OPA-GMR had to exceed 2.0 versus at least one licensed comparator, with the pre-specified adjustment for the two comparator assessments. Pax31 met the superiority criterion for all four assessments, demonstrating a strong functional immune response to the three unique serotypes and cross-reactive to NTD. Together with the 28 shared serotypes, VAX31 therefore met the criteria for all 32 pre-specified primary assessments in adults 50 and older. For the primary immunobreaching analysis, comparing Vax31 recipients aged 18 to 49 with those aged 15 to 64, as seen on slide 25, Vax 31 met the known inferiority criterion across all 32 evaluated responses, demonstrating consistent immune responses between these age groups. These results provide the immunologic foundation for our planned request for an indication beginning at age 18, subject, of course, to regulatory review. Finally, let's turn to the individual competitor specific results on slide 26. Against PCB20, VAX31 met the more stringent 0.667 non-inferiority threshold for all 20 of 20 shared serotypes. Against PCB21, 17 of 19 shared serotypes met the 0.667 threshold. The two exceptions were serotype 3 and 12F. While neither met that higher threshold versus PCV21, the lower bound of their 95% confidence intervals both exceeded the historical 0.5 threshold. Or setotype 2SF, other immunological measures, including similar fourfold responses rates and supportive IgG responses were consistent with a robust immune response. Serotype 3 is biologically atypical. Differences in serum immune responses have not consistently translated into proportional differences in biological effects. The complexity is intrinsic to serotype 3 rather than specific to VAX31. Now, given the current adult epidemiology, we expect the PCV21 comparison to be a particular focus of U.S. regulatory review. PCB20 remains an important license comparator. Taken together with the successful primary analysis, we believe these data provide a strong foundation for the Plan BLA. I will now turn the call back to Grant for a few concluding remarks and next steps. Thank you, Luis. Opus 1 marks a defining milestone for VACC site. Vax31 met all pre-specified primary immunogenicity endpoints in this pivotal phase three trial, including immunobridging, while demonstrating a safety profile similar to the licensed comparators. We took on a higher immunogenicities standard with a broader spectrum vaccine and delivered. These results reinforce our conviction in Vax 31's potential to become a best-in-class pneumococcal vaccine and provide strong clinical validation of our carrier-sparing platform. Turning to slide 29, Opus 1 will be the cornerstone of the BLA application, supported by Opus 2 and 3, with results expected in the first half of 2027, along with a manufacturing consistency study. Following completion of the remaining clinical and manufacturing work, we expect to be in the position to submit our U.S. Biologics Licensing Application for FDA review in the first half of 2028. Turning to slide 30, we have already made substantial investments to prepare for commercialization. We have completed the build-out of a dedicated manufacturing facility designed to produce over tens of millions of doses a year, with the finished product to come from the new line we're building in Greenville, North Carolina. Together with our existing supply chain and the medical and commercial capabilities that are building these investments should enable us to capitalize on this significant opportunity beginning with the adult market the opportunity extends beyond adults with important pipeline milestones ahead noted here on slide 31. we expect dax 31 infant phase 2 results from the primary immunization series and booster dose either sequentially or together by the end of the the first half of 2027. We are also advancing VaxXL, our third-generation PCV, which is in preclinical development to help maintain our anticipated leadership position. For VaxA1, our group-based strep vaccine candidate, we expect phase one results in the second half of next year. Before we open the call for questions, I want to thank our study participants, investigators, and everyone at Backsite who made this milestone possible. More than a decade ago, we set out to protect humankind from the consequences of bacterial diseases. These pivotal results bring us one giant step closer to delivering on that mission. We are tremendously proud of this achievement and focused on the work ahead. Thank you for your continued support. Operator, we are ready for questions. Thank you. We will now begin the question and answer session. if you'd like to ask a question press star 1 on your keypad to leave the queue at any time press star 2. once again that is star 1 to ask the question our first question today comes from dave risinger with leering partners your line is now open thanks very much and uh congrats brandon team on the phenomenal data so i have uh two questions please. First, can you discuss your vision for your pneumococcal conjugate vaccine franchise to lead the market and the durability that you expect of that leadership? And also comment on the 0.67 non-inferiority margin creating a new bar for future PCV competitors. And then separately, we've received a lot of questions about competitor Merck's serotype 3 coverage. So I was hoping you could contextualize the results that Merck presented at the Pneumococcal Disease Conference in May in Copenhagen for its 15-valent, which showed no correlation between OPA, GMR results, and actual serotype 3 protection, and just add some perspective on why that dilutes Merck's serotype-3 messaging. Thanks very much. Thanks for the question, Dave, and appreciate the congratulations. Super exciting for the company, and I think super exciting for public health. So, yeah, I appreciate the questions. Our vision for the franchise, you know, we've had a really long-term mindset from the beginning. You know, we started with VAX 24. We felt like we could stretch to VAX 31. We've proven that now. And, you Know, this is a class that has had extremely long durations of leadership. So, right, started with Prevnar 26 years ago. that franchise still possesses the majority of market share today, both in the adult and infant class. And I think we view this as the baton being passed to our PCV franchise in light of the data that we've been able to generate. And, you know, as much of a breakthrough as the historical chemistry was, you Know, we realized that there was a limitation some time ago when we started focusing on this back in 2015. And we have an opportunity to rise to the occasion of the need for substantially broader coverage without sacrificing the immunogenicity to give us confidence that we're going to continue to see really good protection against pneumococcal disease. So we believe that we are really set up for a long-term type of franchise here. We say that because given the coverage of Vax31 already at 95% of circulating disease in adults in the U.S. and even higher in Europe, it's closer to 98% there, we are already effectively blanketing the disease coverage today. The theory behind VaxXL is a recognition that we believe we do have additional headroom to go further, but that's really going to be driven by the epidemiology. At this stage, additional serotypes add really de minimis incremental coverage. So for us, we want to have a level of readiness with VaxXL to the extent serotype replacement makes a meaningful impact on the coverage for Vax31. But frankly, we think that will come predominantly from widespread use of Vax 31. That's how the class has unfolded, right, Dave? when you use a really broad-spectrum vaccine, those contained serotypes tend to be taken out of circulation. So, we want to have readiness for that, but we believe that VAX31 is going to be in a position to durably lead this space, but мы still have some more work to do to get the BLA in, et cetera. But for us, that's how we're thinking about the franchise sooner and later. As to your second question, appreciate that reference to the recent ISPPD data. So yeah, This is a widely known phenomenon that serotype 3 is very much of an outlier in this class. It truly is the exception to the rule. What we have seen with this class of vaccines is that they provide really effective outcomes associated with the prevention of disease, carriage, and transmission. The exception to that is serotype three. So even though it has been included in the licensed pneumococcal conjugate vaccines since 2010, it continues to circulate at the highest rates. It is effective. It was proven in the CAPTA trial in adults that we do see the prevention of disease with pneumocockle conjugate vaccines. But unfortunately, the durability of protection is not consistent the way it is with the other serotypes that had been included. And that carries forward to the actual carriage of the bacteria and then its transmission from one person to another. So there was some initial excitement when, as you say, the 15-valent PCB showed higher titers against serotype 3. But frankly, there was real skepticism about whether or not that would translate to anything meaningfully clinically. So when it was first received, that was the reaction. So it was a prove it kind of moment. And what happened was there was work done to look at these higher antibody titers to see if it had effect on carriage, which is the leading indicator of what will turn into transmission. That was reported in May of this year at ISPPD. And the reality is there was no effect, even with higher OPA titers, it did not produce any change in the rates of transmission. So I think the reality is we just have not cracked the code on serotype 3 as an industry. We believe our data puts us in a really good position with the comparator vaccines by virtue of the clarity of what we've produced in evidence today. So yeah, serotype three is very much the exception to the rule in this class. Thanks so much. Thank you. Our next question comes from Seamus Fernandez with Guggenheim. Your line is now open. Hello. Hey, guys. Congrats on the data. And just a couple quick questions. How, you know, you see these data potentially offering incremental information relative to the opportunity in the pediatric setting in particular, just given the fact that that's your next major catalyst. It does seem like the data on 22F is particularly encouraging here, but just interested to know how you guys are thinking about that opportunity. And then incremental to that. As we think about the commercialization and the opportunity to commercialize, just a timeframe of the filing, the launch potential, if you could just provide us a little bit of the out-of-the-gate supply that you see being available, given the opportunity to potentially dominate this market on the adult side very quickly. Thanks. Awesome. Thanks, Seamus. I think that's a five-parter. So, I will start, and then I will distribute to the team as we go through. So thank you for the questions. Yeah, so obviously, the data in adults, as we said, we think is extremely clear. The next two studies that we'll read out for us will also be in the adult segment, but as we've guided, we have this fully enrolled phase two study with Vax31 using the same formulation that's read out today, but bracketed with a slightly lower dose and a slightly higher dose. So we're going to learn a lot as it relates to guiding to the appropriate dose as we think about a phase three program going forward. I think we need to be careful about adult data and how that can read through to infants. We do have the benefit now of having conducted both adult and infant studies with VAX 24. We have the VAX 31 adult studies now, phase two and phase three, but we've yet to be able to connect the dot to the infant segment. You pointed it out yourself, the fact that 22F was one of those serotypes where we expected to miss on the relative comparison to Prevnar 20. We got a really nice surprise when we saw the results with this 4.4 microgram dose of 22F in adults, where we did see a meaningful improvement relative to what we had seen in the prior study. So for us, that makes us feel really good. As a reminder, in the Vax24 formulation, we had only dosed 22F at 1.1 or 2.2 micrograms. So we had, you know, had confidence that doses have worked out for us. We've seen a really nice, consistent dose response. So, we have 22F dosed at both 3.3 and 4.4 in that upcoming study. So yeah, that makes us feel good about things. 22F is the second highest circulating serotype. So it is a priority. And it is one of the things that, you know, gives us a bit more hope heading into that particular outcome. But I think we need to be careful about, you know, going too far with the adult results. Obviously, the safety is clean. That's super encouraging. The robustness of the immune responses across the board is encouraging. We just need to being clear that these are two different populations that we're talking about. But the VAX24 data was positive, right? We hit on all of the incremental serotypes in that study from a, in the VAx24 PEDS study from the superiority perspective. We hit on all the key circulating serotypes at post-dose three, and the handful of misses that we had in that setting were all with low circulating or not circulating at all serotypes. So we felt very good about what we saw with Vax24. And the key thing is to flex on the incremental coverage that comes from Vax31, and it's 11 incremental serotypes relative to Prevnar20. So yeah, this data gives us a lot of confidence given how we performed versus Previnar20. And as a reminder, we don't have that same complication that we have in the adult segment. It's Prevdar20 as dominant market share. So it is a bit more of a straightforward set of circumstances we think about that data coming forward so with that uh you asked us about commercialization vla timing launch potential supply uh why don't i hand it to mike first to make some comments about commercialisation then i'll hand it andrew to talk about the vla time or we can flip it you want to do it yeah maybe i'll start jimmy thanks for the question this is andrew and turn it over to mike uh look to your question you know we are preparing for not only the vlas submission but readiness for approval and launch the product so to your question i would look at think about three separate tracks that we're running in parallel first would be the bla enabling activities right as grant mentioned the office one study is absolutely the cornerstone of that bla application but it's not the only component but we've got the opus two and office three studies those are now fully enrolled we expect data for those in the first half of next year as noted and we've also got the manufacturing consistency study that we need to both align on commence and conclude and across all these activities both clinical and commercial as we have been doing for the last several years we'll continue to gauge with the fda on that to ensure that the vla we ultimately deliver that meets with their uh support so that's track one and then track two would be just manufacturing readiness activities as we uh you know prepare for a launch that includes building inventory levels to meet the opportunity in the adult markets i'll help mike talk about that in a minute and then the third track would just be commercial readiness activities uh from both the medical affairs and commercial standpoint so we feel like we're in a good position there's certainly a lot to do but you know with this data in hand i think it's a uh we couldn't imagine a better start uh to enable us to pull all this together to not only submit the bla but to deliver a product that we can successfully commercialize in the market and just before we hand it to mike uh just to to pick up where andrew left off as it relates to the supply just to be clear we have been manufacturing with our cmo material for quite some time we are in the mode of not only validating the manufacturing process but as andrew hinted at already beginning to build inventory so yeah we are already preparing for a launch consistent with the kind of profile that we've been expecting, although we will say that these data exceeded our expectations. But yeah, we are going to be ready for the inventory build. And as we commented in the prepared remarks, we've already built out that dedicated facility for which we can make tens of millions of doses per year. That facility is already in production and being validated itself. So it should be a relatively quick handoff from the initial supply to the even larger supply. With that, let me head it to Mike to talk about launch potential and commercialization. Yeah, of course, Seamus, thanks so much. We're thrilled about these data from a commercial perspective, of coarse. We feel we have a best in class vaccine with the broadest coverage available, so we're excited. I think, first of all, we've been able to develop a really strong team starting out of the gates really well. I think secondly, this market is highly concentrated in the adult space, specifically around retail pharmacies and large health systems in the U.S. So that concentration gives us the opportunity to really focus in at launch and prepare ourselves effectively. And we feel like we're on a really great path to do that. Maybe third, I'll say is we're preparing for recommendations. So obviously in the united states that means getting ready for a strong acip recommendation and generating the data necessary we feel like we're on a great uh start to that work uh already and in the event of course that the acip is either non-functioning or you know perhaps lack some of the credibility that it had in the past we're really encouraged by the fact that other recommending bodies like aafp ama aap vaccine integrity project are all coming out very proactively with vaccine recommendations over the course of this respiratory season which gives us very strong confidence as well there so we'll continue to monitor that progress but we're really excited about the opportunity in front of us and feel like we will try our best to put pressure on on our supply to deliver. Thank you. We'll take our next question from Jonathan Miller with Evercore ISI. Your line is now open. Hey, guys. Thanks for taking the question, and congrats on a really stellar result. I want to start by asking about some of the cross-reactivity comparisons that you obliquely mentioned on the call a little bit, but I want you to get a little deeper into that. So you're You're looking at, for instance, serotype 20B, cross-reactive from serotype 20C. That's already in the plan. But I'm curious about other serotypes where there may be cross- reactivity, other things that are not formally included in the shot that might be cross reactive with serotypes that are in the shot and whether there's potential for showing analyses on those cross- reactive serotypes going forward. And then secondarily, I guess I'd love to ask about the things that aren't in today's release. Obviously, you've got a ton of data on secondary endpoints, et cetera, et cetera, that you haven't presented today. When should we expect to be seeing more detailed information from the deeper analyses from this trial? Hey, John, thank you so much. Really appreciate your use of the word stellar. So as it relates to the cross-reactivity, yeah, so we've already, you know, shown the 20B data. There are a few more cross- reactive examinations that will be performed. You know, today is the top-line result delivery. So between top- line and final, those data will emerge. And so we're going to not go further than that in this moment. But yeah, that is a feature of Opus 1 and something for people to look forward to. As it relates to the secondary endpoints like superiority and statistically greater immune responses, those fall into the same category. But as we have defined at the setup, we've said how those will be defined. So to the extent statistically greater comes from the lower bound to the confidence interval exceeding 1.0 it does it will include a multiplicity adjustment but you can look at the data that's in the presentation and get a sense for how those things are likely to fall out and those will be incorporated in the final results thank you and we'll take our next question from roger song with jeffries your line is now open Great. Congrats for the real blue sky scenario for the readout. Thank you for taking our question. A couple of questions from us. The first one is understanding the primary endpoints comparing two vaccines either or to either stand non-inferiority criteria. Just curious about the importance of the individual vaccine approval, the comparison. For example, have two misses against the PCV21 or CABACSYF. How should we think about FDA regulatory consideration and then maybe the commercial adoption? 12F is missing PCV 21, but pretty high for PCV20. And then on the other secondary endpoint, just to follow on the previous question, Chris, any of those key secondary endpoints will be particularly impactful for the BLA package and the overall profile, for example, the security and the statistical greater. And then that's number two. And the last question, just can you comment on your assay quality the, because you use the historical study and the modeling to predict potential misses. Since this is better than your expectation, maybe the 12S is outlier. And then comment on the variability of the DLSA and then how you're confident about the quality and then for the FDA review. Thank you. Thank you, Roger. I appreciate those questions. So, why don't I hand it to Luis Jodar to open up with your questions with regard to those 11 overlapping serotypes in the IVAN-OR and the importance of the individual myths. Do you want to take that on, Luis? Luis Jodar Sure. Thank you. Thank you for the question. I'm just going to try to explain very succinctly for everybody listening the statistical framework for the 11 shared set of types. So for the set of times that are present in both licensed comparators, we have two pre-specified comparisons against PCV20 and PCV21. And success required non-inferiority to at least 1. So as you know, having two comparisons gives you two statistical opportunities. So therefore, what a pre-specified multiplicity adjustment, in this particular case, the Hopper adjustment, what it does is to control any false positive errors associated with that. That doesn't mean that it relaxes the 0.667 or the non-inferiority margin. In fact, if only one competitor provides evidence of non- inferiority, that comparison has to meet a more stringent one-sided p-value threshold of 0.0125 rather than 0.225. So, the adjustment is a statistical safeguard, not a mechanism to facilitate success. And with regard to the FDA, what we've learned about the FDA. The historical practice is compare with the broadest coverage PCV. And I think as you have been looking at the evolution of the epidemiological landscape, the FDA has indicated during our discussions that given the current U.S. epidemiology, they viewed PCV21 as a particularly relevant competitor. We incorporated that feedback before the data were known. I think what is more important here is that regardless of which competitor regulators ultimately places greater emphasis on in its review, our data set includes pre-planned individual competitor assessments against both PCV21 and PCV20. So, FDA will have the full head-to-head immunogenicity profile against each licensed vaccine available for review. We've mentioned also about the importance of these two misses against PCV21. I'd just like to remind you that those two misses were against the most stringent 0.667 non-inferiority comparison. Both of these serotypes met the historical 0.5 non-interiority comparison. And additionally, both of these set of types met the 0.667 stringent comparison against BCD20. We see these statistical misses as part of the totality of the evidence, And this is how the FDA has traditionally reviewed and evaluated this vaccine. So we feel very confident with the data set that we have presented today. And I will turn about to John. Yeah, thank you, Luis. Yeah, I appreciate you kicking that off. Yeah, Roger, I mean, the bottom line is Opus 1 was a complete success. And, you know, we acknowledge that ultimately, if everything goes the way we plan, we will be competing with each of these two comparators in the marketplace. We think we have very clear data. We have a product with 10 or 11 more serotypes in the vaccine. And we know that perfection is not the price of admission in this class. every pneumococcal conjugate vaccine that is on the market today was licensed with at least one miss to as many as six misses in their formal co-primary endpoints of their pivotal studies. So we feel extremely good about the setup for Vax31. And let me transition to your second question. You asked about the secondary endpoints and their criticality. So yeah, what's left to come is those statistically greater analyses on the overlapping serotypes and superiority for incremental serotypes relative to the individual vaccines. In our view, superiority is rarefied air in this class. And greater immune responses, for that matter, are rarefied air. It's really icing on the cake. It has never been the case that there's been more than one serotype shown to be statistically greater in a pivotal study on a relative basis for overlapping PCN serotypes. So you can see that the data is suggesting that we will be substantially higher than that. So, yeah, we're super excited about that. You know, the cross-reactivity is coming. We feel great about the setup for us, 31-bit vaccine based on this data. I think the position to look at a label for 32 coverage. So we feel great About it. You asked about the OPA assay. What we would say is, you know, when we were looking at the phase 2 data and making projections, we will acknowledge that these data that have come out have had less variability than what we had seen with the prior assay used in phase two. And if you look across the pivotal phase three studies for the comparator vaccine, the variability was tighter than indicated in either of those two studies. So yeah, this was something that probably worked in our favor. So yeah, everything worked extremely well and in a very clean fashion to put us in a position to end up with a result like this. I'll just add, in terms of the variability of the assay, Roger, we did do validation prior to starting the Phase 3. We looked at a number of parameters that include demonstration of reproducibility or variability there is a who standard in terms of what you need to meet to move forward in phase three and in terms assay variability we met those standards thank you jim thank you so much thank you we'll take our next question from celine syatt with mizuho your line is now open great uh thanks for the question guys and congrats on the uh the great data set um just one for us just the commentary that you guys provided you know in the press release in the slides etc on the fda focusing a little bit more on pcv 21 given the given the the way the population is today um are you hinting at all here that you know the fba or or you guys think that pcb 20 will eventually get pulled from recommendation and if that were to happen what would be the commercial implication here for you especially considering that that pcb 21 does not have stereotypes 4 and 19f hey thanks for the question celine uh well let me just first say uh no we are not suggesting that uh pcb20 is going to get pulled from the market i think if anything no no no sorry from recommendation recommendation sorry recommendation yes sorry just kidding no i i don't we're not making that suggestion either um uh you know louis touched on it um you know the the the commentary is really to reflect the following which is historically it's always been extremely straightforward to look at a novel, more broad-spectrum pneumococcal conjugate vaccine. You compare it to the marketed standard of care product that has the broadest coverage. That was pretty straightforward when the history was just layering serotypes on top of overlapping serotypes at the base. So what's different about this moment, as we set up in the prepared remarks, we have two standard of care vaccines that are not recommended with any differential recommendation and they have non-overlapping coverage. And so the reality is in the history of the class, you're always comparing against the most broad spectrum comparator. In this moment, that is capexiv, the 21-valent vaccine. So the regulators have expressed a preference for that comparator, but it's indisputable that the 20-valence vaccine still has an important role, particularly given the epidemiology as it has shifted, right? What was the expectation was that those historically controlled serotypes, some of whom had disappeared altogether, would stay that way. But serotype 4, which is the best example, has reemerged very aggressively, and it requires pressure to ensure it does not begin to circulate at even higher levels. So both of the vaccines today are playing a vital role in suppressing disease. We just believe that in a single vaccine that covers all of those serotypes, we have a much better solution. Okay. All right. Thank you very much. Yeah. Thanks, Lorraine. Thank you. Our next question comes from Nick Jennings with Goldman Sachs. Your line is now open. Hi. This is Nick on behalf of the Goldman SachS team. Congratulations on the strong data. First, can you contextualize the extent to which regions you're able to commercialize independently versus partnering and frame the global opportunity vis-a-vis the U.S. And separately on the evolving next-generation competitive landscape developing, do you see any other higher valence PCV programs in development for adults or pediatrics that should rival 31 valency? And when might you expect to move forward VaxXL into the clinic as your next generation? Thank you for that question, Nick. Mike, do you want to touch on the kind of global prospects? Yeah, sure. So thanks for the question, Nick. So first of all, you know, PCV obviously is a very strong developed market globally for pediatrics and adults. So maybe to comment first on adults and keep the area of focus here, you know, we are focused on the U.S. first for our launch strategy. We obviously have completed the clinical program in the United States and we'll continue to focus on that area. it represents the majority of the volume today and the market opportunity today globally however we are very encouraged by the international growth for adult immunization and pcb immunization worldwide we've seen numerous markets come online in the last few years much to the thanks of the of the efforts by uh pfizer and by murph we've see in japan come online numerous european markets come online canada australia etc so you know i think as the the world starts to expand their global reach for adult pcb pcb vaccines we see the growth of the market coming internationally but obviously the lion's share of the in terms of value and volume is coming from the united states so we'll focus on both of those areas um you asked specifically about how we will commercialized you know our plan is to go this alone today we are focused on that commercial build in the united states and have started to that effect of course as we think about external markets and ex-us markets we'll think really strategically about how we might want to partner in local markets or ex-u.s markets to expand our reach more quickly it's obviously a little more efficient to do that with a partner at some point in time but not necessarily necessary especially in some of the key markets so we're going to keep that option open and continue to think about the strategy um maybe i'll turn it back to grant for the second part of that question yeah thanks mike uh so yeah nick as it relates to the competition uh it's it's been you know obviously something we've been laser focused on as we've ben uh dedicated to this class for some time now um you know i would just go back to the comments that were made from other sponsors uh a number years ago where it was clear that going beyond 20 or 21 conjugates using the conventional technology did not look practicable. In fact, that's why shifting the goalposts the way that Merck did with their 21-valent was a clever way to leverage the technology in ways that honored the fact that getting more than 20 or21 into a single formulation was not practical. In the meantime, other efforts to develop PCBs beyond that have fallen away. We had a 21 valent that fell away, a 24 valent that fell from the competition, a 25 valent, that more recently fell away in the adult space. And to our knowledge, there are a couple of programs that are in very early development that are talking about 30 plus. I think there's one in preclinical, there's one in phase one development, but there's been no data generated, and these are using novel approaches for which there's no clarity that they're going to be able to deliver something beyond what's been shown to date. And now, and I kind of forgot to answer this when Dave asked it earlier, we have established this higher bar for the definition of non-inferiority of 0.667. That is going to it only that much more difficult to be able to show non-inferiority in the context of a 30-plus valent vaccine. So we do feel incredibly good about this data, the prospects it has for the potential of Vax31, and the potential durability of Vex31 going forward in light of that fact set. Thank you. And as a reminder, to ask a question, you may do so by pressing star 1. Additionally, in the interest of time, we ask that you limit yourself to one question. We'll go next to Tara Bancroft with TD Cowan. Your line is now open. Hi, good morning, and really congrats on this fantastic data so uh my question so i want to go back to what you said your comments on on recommendation um from a couple questions ago i just want to get your your thoughts on the possibility of a preferential recommendation with these data and even if there's the need or desire for that you know given everything that you've said about um the increased coverage anyways um so that's that's just a confirmatory one and then some clarity on uh the timeline to bla so So I know it's quite a ways away, but I'm just wondering, you know, the manufacturing study, that's probably the gating factor for that, right? Like, mostly trying to see, do you need Opus 2 and 3 to file? Do you need the manufacturing study? Basically trying to say, do we need the Opus 1 and 3? Trying to see if there's any way, especially with this caliber of data in hand, if you could file sooner. Thanks. Thank you, Tara. Really appreciate that. Yeah, as it relates to the recommendations, I mean, we need to be careful, right? I mean we're thrilled with this data. We think it's incredibly clear. Preferential recommendations are not the norm. So, you know, what we look at is how has the performance of broader spectrum vaccines gone? And as we've said time and time again, coverage is king. And, you know, the broader spectrum vaccines have dominated from a market share perspective. And so, you know, independent of whether a preferred recommendation would be granted, we think we have the product profile that warrants the lion's share of the market. Of course, if it came in the context of a preferred recommendations, then it happens really fast. We saw that with Shingrix. You know, It has been the case that, at least in the context of the 21-valent, that was expected or at least guided to being in a position to obtain a preferred recommendation. What stopped that from happening was the emergence of some of those historically controlled stereotypes, like stereotype 4. So that is not going to be a problem for us, but I can imagine that we would not do anything like that. But we certainly think we have a profile that is superior than that precedent. So I would appreciate the thought, but I think we stop for that in the context of what we have in this moment. But, Andrew, do you want to talk about the BLA question? Yeah, Terry, to your question on timelines, you know, as you saw, obviously, guiding to the submission of a BLA in the first half of 2028. And Opus 1, you know, as I mentioned, is certainly the cornerstone. In Opus 2 and Opus 3, you know, we need the number of subjects exposed across the studies to meet the opposite safety database requirements. So those are important, perhaps not for the immunogenicity data. That is more relevant for the recommending bodies and potential approval, but we need the safety, the number OF subjects exposed from a safety data perspective. And, you know, the Opus two study in particular should be quite interesting. or Opus 3, excuse me, as we look at the Vax31 administered to subjects who previously received a lesser valent vaccine. So, we can get into that discussion at some later point about how that might play in the recommending body setting and from a commercial perspective. But so, we've got the Opus 1, Opus 2, and Opus three studies, the latter two reading out in the first half of next year, right, with this data set in hand, now looking to align with the FDA on the manufacturing consistency study, all those components comprised of BLA-enabling activities that put us in a position to submit to BLA. But as I said, it's not just about submitting to BLa. It's about readying ourselves for a successful commercial launch. And in that context, all the manufacturing activities to build the necessary inventory and then standing up the medical affairs and commercial efforts to deliver on the opportunity. So rest assured we will be looking to move as quickly as possible. But, you know, couldn't be more thrilled with the data we have in hand to get an aid in our ability to meet all these objectives over the coming months as we're ready for that submission. Great. Thank you so much. Thank you. Our next question comes from Jason Gerberry with Bank of America. Your line is now open. Hey, guys. Let me extend my congrats on the data. So one question that I had was around the competitive pipeline of 30-plus valent PCVs. So you guys will be at a minimum a couple of years ahead of any of those approaches. So just want to confirm, would your assumption be that VAX31 would likely be the requisite active comparator with the 0.667 non-inferiority lower bound or margin? And in the past, you guys have talked about the sort of 25% average higher immune responses versus PCV20 on the basis of your prior phase two. I think they convey that there was no trade down on some of the legacy strains. And so I think directionally we can infer that by looking at the plots here, but I'm wondering if you can confirm that, even if it's just directional. Thanks. Yeah, thanks, Jason. So, yeah, as it relates to the 30-plus pipeline, yeah early days, right? So to the extent it's hard to imagine that we wouldn't be in a position to have our product on the market and to the extend our product would be approved given those precedents that I cited earlier, we would most certainly expect that the comparator product in development would need to be compared to VAX 31. And as we've said publicly in the past, it's our belief that the .667 non-inferiority bar is a class-wide FDA position. So yeah, I think that that is very much our expectation, and so we believe that we have raised the bar effectively for companies that come along afterward. So yeah. I think, that's going to be a very difficult challenge for others, and obviously sets us up quite well. Let's see. And then, what was the second question? The immune response, and then being in this relative to PCV20 and PCV21. Oh yeah, yeah, on a relative basis. Yeah, Jason, good question. So, you know, if you look at the average immune responses on the raw data, you Know, we're definitely delighted across the board. We're seeing average higher immune responses against each of the comparator vaccines. But I mean, the key thing is the data that we presented today. That's really the thing that matters most is the successful outcomes from a GMR perspective. So yeah, we're delighted there was some movement here or there. The bottom line is we're thrilled with the outcome. And you can just look at the number of serotypes on a comparator basis and how many of them are to the right of 1.0 for the lower bound. And you Can see that it's mission accomplished with regard to broader coverage and maintaining immune responses. You know, we have gotten past the consistent drop across overlapping serotypes, and we have, you know, arguably more to the right of one than to the left of one, certainly for Prevnar 20, and that is an incredible outcome. Yeah, thank you. Thank you. Thank you, our next question comes from Tom Schrader with BTIG. Your line is now open. Good morning. Obviously, fabulous data. Really quite related to what you just answered. In terms of the platform, do you have headroom versus Vax24 to Vax31? Do you have confidence that you're not done and kind of relevant to that? Do You think this world of vaccines might move to the like other worlds of vaccines where you could update? So for instance, you could add a little more 12 or something else that breaks out without going through this gigantic process thank you uh well thank you thank you tom uh jim do you want to take that one yeah so you know obviously you can see that where we ended up with our results for the 31 we believe that there is some incremental headroom uh right now we are covering the vast majority of circulating stereotypes you know and adding an incremental stereotype or two Relative to the gain in coverage, we don't see specifically a need for that at this time. But, you know, this space has evolved over time. There's a phenomenon of serotype replacement where other serotypes have emerged as vaccines were effective. So we're preparing for that, and we believe we will move forward with that if necessary. Yeah, and, Tom, I think you're pointing out the phenomena of carrier suppression that has governed this class. You know, we haven't talked a lot about it in the context of today's conversation, but, you know, that was the underlying feature that I referenced when prior sponsors were talking about really being restricted to 20 or 21 conjugates in a single formulation. I think we have proven that our carrier sparing technology and our site-specific conjugation technology is allowing us to not only push on the number of conjugates in a single formulation that, of course, turns into broader coverage, but also we have shown that we can use more of the protein carrier than we would have originally expected and not pay a penalty for it. So we are definitely uncharting or we are charting new territory as it relates to how we have moved toward higher doses that have yielded higher immune responses. You know, in the adults, we saw lesser impact of increasing doses than we even saw in the infant segment. So, yeah, I think we feel great about how the platform is performing. I think it bodes well for, you know, future expandability to the extent the epidemiology warrants it. and, you know, just continues to, you know, get us excited about the infant data that will lead out next year. And in terms of your question about if we make improvements to existing serotypes, that would be considered a new product, and you would have to do that. But if we're going to do an XL at some point, those types of improvements could be considered to be added as well. Okay, thanks. Congrats again. Thanks, Tom. Thank you. Our next question comes from Carter gold with canter your line is now great great good morning grant and team let me echo the earlier congratulations um i guess uh real quick just on the back of these data the strength of these data is there any shifts and how you guys are thinking about the commercial build or things that are going to get accelerated or pulled forward based on the strength of this data which you know exceeded your own expectations thank you carter appreciate that question uh i i have not checked my email to see if mike they could send me some new requisitions, but that could come. Mike, how would you answer that question? Yeah, look, obviously, we're thrilled by the data and it exceeded even our expectations. So, you know, we are really excited. I think that the plan of attack is still the same. You know, this is a really concentrated market, Carter. I hate to say straightforward because it's super complicated, of course, but we will spend our time focused on the retail pharmacy segment and large health institutions. So it all starts today with making sure that these data are clear, making sure we can communicate it well to the medical and scientific community over the course of the next coming weeks and months to make sure that confidence is built in our organization and build quickly. So yes, of course, the requisitions will be coming to grant very quickly, but we are ready and feel like we're in a really great position. And I think feedback so far from all of you has been really great and we'll hear from the scientific community over the course of the next few weeks that we're looking forward to that's good thanks goddard thank you our final question today comes from joseph stringer with needham and company your line is now open hi hi thanks for taking our question and congrats on the great data a commercial question just on the adult market growth potential you had mentioned several growth drivers of that segment just curious if you think the vax 31 adult data today could potentially drive that even further to the upside meaning if there's a vaccine with better overall coverage and a better profile than the standard of care vaccines could could one or more of those adult growth drivers be supercharged could it could it kind of drive the adult growth even higher than expected in the total market over that $20, $30 to $12 billion estimate? Thanks. Yeah, it's a good question, Joey. I mean, I'll let Mike chime in in a second. But, you know, just going back to the conversation at the ACIP when they decided to lower the recommendation for adult vaccination in the U.S., which used to be when you aged into the 65 and up age group, that's when you would be recommended to get a pneumococcal conjugate vaccine. They lowered that age down to age 50. And there was a very robust conversation about the durability of protection and the appropriateness for a revaccination when people turned 65 after having received a vaccine when they turned 50. And the conversation very specifically focused on the high-valent vaccines coming with specific reference to VAX 31. So, yeah, I think to the extent there's already a movement toward that, the spectrum of coverage that could be provided in that context only reinforces the notion of the potential value of that. So yeah, certainly directionally will be valuable. So that's my first reaction. But Mike, how do you think about it? Yeah, I start certainly with recommendations. And so, you know, if we think about the U.S. first, and then maybe I'll talk about OUS, Joey, but U.F. first to Grant said, you know, there's been this conversation about, you know, when will the booster dose be necessary? I'll also offer that, you know, the recommending bodies, ACIP or other, will certainly consider the need to revaccinate previously immunized adults with PCV13 or 20 or 21 or PPSV23. And I think that will, the recommendation there can obviously substantially increase the size of the market. Also, I think importantly today in the United States, the 50 to 64-year-old category has a lower immunization rate than the 65-plus category. And so to the extent that that 50 to 54 category can grow and we can effectively communicate with that category, there is opportunity, of course, there. Lastly, I think also the value of the product, the perceived value in the marketplace and the pricing, will play a role in value creation. Obviously, we have some health economic data to generate for the recommending bodies and for payers across the United States. So I think those are the levers as we see them. OUS, I think what we've seen so far is similar to what we saw in the beginning for PCV vaccinations for adults in the United states. So most of the recommendations are 65 plus. Those catch-up immunizations are starting to occur, but the speed of those XUS could be very helpful to the market size. And then do the recommending bodies in other countries move down to the 50 to 64 category as the United States did? So there's still a lot of market shaping and market development to be done in these markets around the world, and we'll continue to to see where the opportunities lie but i think those are the big drivers thank you this does conclude today's question and answer period i will now turn the call back to grant for any final remarks thank you operator uh well we can conclude todays call i do want to just uh thank uh not only the study participants investigators and everyone at vac site who i referenced earlier but i also want to acknowledge the investors who have supported our efforts today our partners who have helped us rise to the occasion of developing the broadest pneumococcal conjugate vaccine ever taken into the clinic it's a real community effort to deliver on a product of this potential importance for public health so we thank you all we really appreciate your support thank you for joining today's conference call this concludes the call you may now