Morning, and welcome to Vaxcyte's conference call to discuss the OPUS-1 phase III top line 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 one on your telephone keypad. I will now turn the call over to Andrew Guggenhime, President and Chief Financial Officer of Vaxcyte. Please go ahead.
Thank you, operator, and good morning, everyone. Welcome to Vaxcyte's conference call to discuss top line results from OPUS-1, our pivotal phase III trial evaluating VAX-31 in adults aged 18 and older. VAX-31 is our investigational 31-valent pneumococcal conjugate vaccine, or PCV, designed to prevent invasive pneumococcal disease, or IPD, and pneumococcal pneumonia. I am joined today by Grant Pickering, our Chief Executive Officer and Co-Founder, Jim Wassil, our Chief Scientific Officer and Chief Operating Officer, Luis Jodar, our Chief Medical Officer, and Mike Mullette, 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 SEC filings can be found in the Investors and Media section of our website. Before we begin, as noted on slide three, I would like to remind you that during this call, we will be making certain forward-looking statements about Vaxcyte, 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 a 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 the risk factors 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 will turn the call over to Grant.
Thank you, Andrew, and we appreciate you all joining us today. On behalf of the entire Vaxcyte team, I am immensely proud to share that OPUS-1 met all pre-specified primary immunogenicity endpoints across all ages studied. VAX-31 was also well-tolerated and demonstrated a safety profile similar to the licensed comparators in the study, Capvaxive or PCV21 and Prevnar 20 or PCV20. 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 PCVs 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 BLA alongside OPUS-2 and OPUS-3 results and a manufacturing consistency study. I will 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 will 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 VAX-31 in context, I would like to spend a few moments to orient you all as to how the category has evolved and the present trade-offs we have an opportunity to overcome with VAX-31 in order to prevent a substantial residual disease burden. Turning to slide seven, the success of pediatric PCVs 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. Broader coverage has historically come with lower immune responses. This was evidenced with PCV20 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 PCV20 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 PCV20 while leaving out nine of the historically important serotypes retained in PCV20. 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.
With the resurgence of serotype IV 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 PCV20, but absent from PCV21. This has resulted in a difficult trade-off for healthcare providers as they choose between two equally recommended vaccines with partially overlapping coverage.
At present, the market is split with a slight edge to PCV20. VAX-31 was designed to overcome these trade-offs by retaining all of the PCV20 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.
As you can see on this epidemiology slide seven, VAX-31 incorporates serotypes responsible for 95% of invasive pneumococcal disease and 88% of pneumococcal pneumonia in U.S. adults 50 and older, a greater proportion than either PCV20 or PCV21. The strength and consistency of our phase II 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 III study. With that backdrop, let's review the approval standard for immunogenicity and the pre-specified framework used to evaluate VAX-31 head-to-head with PCV20 and PCV21 in OPUS-1.
Turning to slide eight, this slide puts the immune response standards in context. Opsonophagocytic 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 VAX-31 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 0.667 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 2/3 of the comparator response rather than 1/2. Farther to the right, the green area represents a lower bound greater than one, which indicates statistically greater immune responses. 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 PCV development.
Turning to slide nine, let's review what VAX-31 needed to deliver to meet the study's primary endpoints. OPUS-1 was a complex study with two comparators, 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 VAX-31 was compared with both PCV20 and PCV21. For each serotype, the primary criterion 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 VAX-31 and PCV20 were compared to establish the OPA GMRs with the primary criterion for non-inferiority requiring the lower bound to exceed 0.667. For the third group, the eight serotypes unique to VAX-31 and PCV21 were compared using the same non-inferiority 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 VAX-31, 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 VAX-31 responses in adults aged 18- 49 versus those aged 50- 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 VAX-31. With that comprehensive setup, as reflected on slide 10, we are thrilled to report that VAX-31 met all 32 pre-specified 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 and outcome that exceeded our expectations. That success continued with immunobridging.
All 32 comparisons across the age groups also met non-inferiority. 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, VAX-31 went 17 of 19. For serotypes three and 12F, the lower 95% confidence bounds did not exceed 0.667 versus PCV21 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 am extremely pleased to be able to share the results of the OPUS-1 study with you today. In terms of the trial design, as seen on slide 13, OPUS-1 is a randomized, double-blind, active control, phase III trial that vaccinated 4,047 adults in the United States, 3,572 aged 50 and older, and 475 aged 18- 49. As shown here, adults 50 and older were randomized equally to receive either VAX-31, PCV20, or PCV21. Adults aged 18- 49 were randomized three to one to receive either the VAX-31 or PCV20 arms respectively, with PCV20 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 after vaccination. Medically attended adverse events, new onset of chronic illness, and serious adverse events were followed through six months. Turning 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 immunogenicity evaluable population across three treatment groups.
We saw similarly high follow-ups in adults 18- 49, with approximately 98% of VAX-31 recipients contributing evaluable immunogenicity data. Overall, these high retention rates provide a robust data set for the pre-specified safety and immunogenicity analyses. Turning to slide 15, in terms of demographics, approximately 2/3 of participants were between 50 and 64 years of age, and about 1/3 were 65 or older, with comparable distributions of sex, race, ethnicity, and body mass index across VAX-31, PCV21, and PCV20, with substantial diversity amongst enrolled participants.
Importantly, more than 1/4 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- 49, as you can see on slide 16, baseline characteristics were generally similar between the randomized VAX-31 and PCV20 safety groups.
For the immunobridging analysis, the relevant comparison is between VAX-31 recipients aged 18- 49 and VAX-31 recipients aged 50 to 64. Because those two age groups were not randomized against each other, expected baseline differences existed. The pre-specified immunobridging model therefore adjusts for baseline OPA titers and the pneumococcal disease risk status rather than relying on raw group means. 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 VAX-31, the blue columns PCV20, and the gray columns PCV21. More severe reactions are represented by darker colors. VAX-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 VAX-31. We see the same overall profile in younger adults here on slide 19.
Reactogenicity was similar to PCV20, predominantly mild to moderate and transient, with the expected local and systemic symptoms. Moving beyond solicited reactogenicity 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 VAX-31 group, and two in the PCV21 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 immunogenicity groups Grant outlined earlier. The first plots on the next few slides show OPA geometric mean ratios, or GMRs, and their 95% confidence interval. For the primary analysis involving two licensed comparators, we also apply the pre-specified Hochberg adjustment for multiplicity. For the first endpoint group, the 11 serotypes contained in all three vaccines, the pre-specified statistical analysis plan required VAX-31 to demonstrate non-inferiority against at least one licensed comparator for each serotype using the multiplicity adjustment we just described.
As reflected on slide 22, VAX-31 met that criterion for all 11 of 11 serotypes. The blue points show the comparisons with PCV20 and the gray points the comparison with PCV21. For serotypes three and 12F, the PCV21 comparison did not meet the more stringent 0.667 threshold, while their PCV20 comparison met the higher 0.667 non-inferiority criterion with the pre-specified Hochberg adjustment. Therefore, both serotypes met the pre-specified primary criterion. I will address these serotypes with respect to the individual comparisons compared to PCV20 and PCV21 on a later slide.
For the second and third endpoint groups, the nine serotypes shared only with PCV20 and the eight shared only with PCV21, the comparison is simpler because each serotype is contained in only one of the two licensed comparators. On the left side of slide 23, VAX-31 met the pre-specified non-inferiority criterion for all nine of nine serotypes shared with PCV20. On the right, it met the criterion for all eight of eight serotypes shared with PCV21. Importantly, every one of these 17 comparisons clear the more stringent 0.667 non-inferiority margin.
Together with the 11 serotypes on the previous slide, VAX-31, therefore, met the pre-specified non-inferiority criterion across all 28 serotypes shared with the licensed comparators. Turning to slide 24, the fourth endpoint group includes the three serotypes unique to VAX-31, 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. VAX-31 met that superiority criterion for all four assessments.
Demonstrating a strong functional immune response to the three unique serotypes and cross-reactive 20B. Together with the 28 shared serotypes, VAX-31 therefore met the criteria for all 32 pre-specified primary assessments in adults 50 and older. For the primary immunobridging analysis comparing VAX-31 recipients aged 18- 49 with those aged 50- 64, as seen on slide 25, VAX-31 met the non-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 comparator and specific results on slide 26. Against PCV20, VAX-31 met the more stringent 0.667 non-inferiority threshold for all 20 of 20 shared serotypes. Against PCV21, 17 of 19 shared serotypes met the 0.667 threshold. The two exceptions were serotype III and 12F. While neither met that higher threshold versus PCV21, the lower bound of their 95% confidence interval both exceeded the historical 0.5 threshold.
For serotype 12F, other immunological measures, including similar seroresponse rates and supportive IgG responses, were consistent with a robust immune response. Serotype III is biologically atypical. Differences in serum immune responses have not consistently translated into proportional differences in biological effects. The complexity is intrinsic to serotype III rather than specific to VAX-31. Given the current adult epidemiology, we expect that the PCV21 comparison to be a particular focus of U.S. regulatory review. PCV20 remains an important licensed comparator. Taken together with the successful primary analysis, we believe these data provide a strong foundation for the planned 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 Vaxcyte. VAX-31 met all pre-specified primary immunogenicity endpoints in this pivotal phase III trial, including immunobridging, while demonstrating a safety profile similar to the licensed comparators. We took on a higher immunogenicity 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 OPUS-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 License 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 we 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 VAX-31 infant phase II results from the primary immunization series and booster dose, either sequentially or together, by the end of the first half of 2027. We are also advancing VAX-XL, our third-generation PCV, which is in preclinical development to help maintain our anticipated leadership position.
For VAX-A1, our Group A strep vaccine candidate, we expect phase I 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 Vaxcyte 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 one on your keypad. To leave the queue at any time, press star two. Once again, that is star one to ask a question. Our first question today comes from Dave Risinger with Leerink Partners. Your line is now open.
Thanks very much, and congrats, Grant and team, on the phenomenal data. I have 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? Also comment on the 0.67 non-inferiority margin creating a new bar for future PCV competitors. Separately, we've received a lot of questions about competitor Merck's serotype III coverage.
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 III protection, and just add some perspective on why that dilutes Merck's serotype III 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. Yeah, appreciate the questions. Our vision for the franchise, we've had a really long-term mindset from the beginning. We started with VAX-24. We felt like we could stretch to VAX-31. We've proven that now. This is a class that has had extremely long durations of leadership. Right, starting with Prevnar 26 years ago, that franchise still possesses the majority of market share today, both in the adult and infant class. 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.
As much of a breakthrough as the historical chemistry was, we realized that there was a limitation some time ago when we started focusing on this back in 2015. 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're really set up for a long-term type of franchise here. We say that because given the coverage of VAX-31 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 VAX-XL 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 VAX-XL to the extent serotype replacement makes a meaningful impact on the coverage for VAX-31. 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 VAX-31 is going to be in a position to durably lead this space, but we still have some more work to do to get the BLA in, et c. 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.
Yeah, this is a widely known phenomenon that serotype III 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 III. 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 CAPiTA trial in adults that we do see the prevention of disease with pneumococcal conjugate vaccines.
But unfortunately, the durability of protection is not consistent the way it is with the other serotypes that have been included, and that carries forward to the actual carriage of the bacteria, and then its transmission from one person to another. There was some initial excitement when, as you say, the 15-valent PCV showed higher titers against serotype III. 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. 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 III as an industry. We believe our data puts us in really good position with the comparator vaccines by virtue of the clarity of what we've produced in evidence today. Serotype III 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 of quick questions. How 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.
Then incremental to that, as we think about the commercialization and the opportunity to commercialize, just a timeframe of the filing, the sort of launch potential, if you could just provide us a little bit of the kind of 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. I will start, and then I will distribute to the team as we go through. Thank you for the questions. Yeah. So obviously, the data in adults, as we've 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 II study with VAX-31 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 phase III 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 II and phase III, 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 µg dose of 22F in adults, where we did see a meaningful improvement relative to what we had seen in the prior study.
For us, that makes us feel really good. As a reminder, in the VAX-24 formulation, we had only dosed 22F at 1.1 µg or 2.2 µg. So we 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 µg and 4.4 µg in that upcoming study. 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 gives us a bit more hope heading into that particular outcome. But I think we need to be careful about 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 be clear that these are two different populations that we're talking about. But the VAX-24 data was positive, right? We hit on all of the incremental serotypes in that study in the VAX-24 Ped Study from a 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 VAX-24.
And the key thing is to flex on the incremental coverage that comes from VAX-31 and its 11 incremental serotypes relative to Prevnar 20. So yeah, this data gives us a lot of confidence given how we performed versus Prevnar 20. And as a reminder, we don't have that same complication that we have in the adult segment. Prevnar 20 has dominant market share, so it is a bit more of a straightforward set of circumstances we think about that data coming forward. With that, you asked us about commercialization, BLA timing, launch potential, supply. Why don't I hand it to Mike first to make some comments about commercialization, then I'll hand it to Andrew to talk about the BLA timing? Or we can flip it. You want to do BLA—
Yeah, maybe I'll start, Seamus. Thanks for the question. This is Andrew. I'll turn it over to Mike. Look, to your question, we are preparing for not only the BLA submission, but readiness for approval and launch of the product. To your question, I would think about three separate tracks that we're running in parallel. First would be the BLA-enabling activities, right? As Grant mentioned, the OPUS-1 study is absolutely the cornerstone of that BLA application, but it's not the only component. We've got the OPUS-2 and OPUS-3 studies. Those are now fully enrolled. We expect data for those in the first half of next year, as noted.
We've also got the manufacturing consistency study that we need to both align on, commence, and conclude. 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 BLA we ultimately deliver meets with their support. So that's track one, and then track two would be just manufacturing readiness activities as we prepare for a launch. That includes building inventory levels to meet the opportunity in the adult market.
So I'll have Mike talk about that in a minute. Then the third track would just be commercial readiness activities from both a medical affairs and commercial standpoint. We feel like we're in a good position. There's certainly a lot to do. But, with this data in hand, I think we couldn't imagine a better start 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.
Just before we hand it to Mike, just 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. 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.
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 hand 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 course. 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 start to that work already.
In the event, of course, that the ACIP is either non-functioning or perhaps lacks some of the credibility that it had in the past, we're really encouraged by the fact that other recommending bodies like AAFP, AAMA, 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 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 to get a little bit deeper into that. You're looking at, for instance, serotype 20B cross-reactive with serotype 20C, that's already in the plans. 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 a potential for showing analyses on those cross-reactive serotypes going forward.
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 c, et c, that you haven't presented today. When should we expect to be seeing more detailed information from the deeper analyses from this trial?
Hey, Jon. Thank you so much. Really appreciate your use of the word stellar. As it relates to the cross-reactivity, yeah. We've already shown the 20B data. There are a few more cross-reactive examinations that will be performed. Today is the top-line result delivery. So between top line and final, those data will emerge, and so we're not going to 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 had defined at the setup, we've said how those will be defined. So, to the extent statistically greater comes from the lower bound of the confidence interval exceeding 1.0, it will include a multiplicity adjustment. You can look at the data that is 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. We will take our next question from Roger Song with Jefferies. Your line is now open.
Great. Congrats for the real blue sky scenario for the readout. Thank you for taking our question. A couple questions from us. The first one is understanding the primary endpoints comparing two vaccine either or to either non-inferiority criteria. Just curious about the importance of the individual vaccine approval, the comparison. For example, you have two misses against the PCV21 or Capvaxive. How should we think about FDA regulatory consideration and then maybe the commercial adoption? Not all F is missing PCV21, but pretty high for PCV20.
On the other secondary endpoint, just to follow on the previous question, Chris any of those key secondary endpoint will be particularly impactful for the BLA package and the overall profile, for example, the security and the statistical greater. That is number two. Last question, just can you comment on your assay quality because you used the historical study and the modeling to predict potential misses. Since this is better than your expectation, maybe the trial F is the outlier. Can you comment on the variability of the assay and then how you are confident about the quality and then for the FDA review. Thank you.
Thank you, Roger. I appreciate those questions. Why don't I hand it to Luis Jodar to open up with your questions with regard to those 11 overlapping serotypes in the either/or and the importance of the individual miss. Do you want to take that on, Luis?
Sure. Thank you. Thank you for the question. I'm just going to try to explain very succinctly for everybody listening the statistical frameworks for the 11 shared serotypes. For the serotypes that are present in both licensed competitors, we have two pre-specified comparisons against PCV20 and PCV21, and success required non-inferiority to at least one. As you know, having two comparisons gives you two statistical opportunity.
Therefore, what a pre-specified multiplicity adjustment, in this particular case, the Hochberg adjustment, what it does is to control any false positive errors associated with that. That doesn't mean that it relaxed 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 0.025. 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 to 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. And 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 vaccines available for review. You'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-inferiority comparison, and additionally, both of these serotypes met the 0.667 stringent comparison against PCV20. 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—
Yeah. Thank you, Luis. I appreciate you kicking that off. Roger, the bottom line is OPUS-1 was a complete success. We acknowledge that ultimately if everything goes the way we plan, we will be competing with each of these two competitors 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.
We feel extremely good about the setup for VAX-31. Let me transition to your second question. You asked about the secondary endpoints and their criticality. 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. Greater immune responses, for that matter, are rarefied air. It's really icing on the cake.
It's 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 serotypes. You can see that the data is suggesting that we will be substantially higher than that. We're super excited about that. The cross-reactivity is coming, and we feel great about the setup for us, 31-valent vaccine based on this data. I think we're positioned to look at a label for 32 coverage. We feel great about it. You asked about the OPA assay.
What we would say is when we were looking at the phase II 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 II. If you look across the pivotal phase III studies for the comparator vaccine, the variability was tighter than indicated in either of those two studies. This was something that probably worked in our favor. 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 III. 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 III. In terms of assay variability, we met those standards.
Thank you, Jim.
Thank you so much.
Thank you. We'll take our next question from Salim Syed with Mizuho. Your line is now open.
Great. Thanks for the question, guys, and congrats on the great data set. Just one for us. Just the commentary that you guys provided in the press release, in the slides, et c, on the FDA focusing a little bit more on PCV21 given the way the population is today. Are you hinting at all here that the FDA or you guys think that PCV20 will eventually get pulled from recommendation? If that were to happen, what would be the commercial implication here for you, especially considering that PCV21 does not have serotypes 4 and 19F?
Hey, thanks for the question, Salim. Well, let me just first say, no, we are not suggesting that PCV20 is going to get pulled from the market. I think if anything—
No, sorry, from recommendation. Sorry.
Oh, got it.
From ACIP recommendation. Yes. Sorry.
I was going to say.
ACIP recommendation. Yes.
No, we are not making that suggestion either. Luis touched on it. The commentary is really to reflect the following, which is historically it has 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.
What is 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. The reality is in the history of the class, you are always comparing against the most broad-spectrum comparator. In this moment, that is Capvaxive, the 21-valent vaccine.
The regulators have expressed a preference for that comparator, but it is indisputable that the 20-valent 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 IV, 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. 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, Salim.
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 are able to commercialize independently versus partnering and frame the global opportunity vis-a-vis the U.S.? Separately, on the evolving next generation competitive landscape developing, do you see any other higher valent PCV programs in development for adults or pediatrics which could rival 31 valency? When might you expect to move forward VAX-XL into the clinic as your next generation?
Thank you for that question, Nick. Mike, do you want to touch on the global prospects?
Yeah, sure. Thanks for the question, Nick. First of all, PCV obviously is a very strong developed market globally for pediatrics and adults. Maybe to comment first on adults and keep the area of focus here. 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 will continue to focus on that area that 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 PCV immunization worldwide.
We have seen numerous markets come online in the last few years, much to the thanks of the efforts by Pfizer and by Merck. We have seen Japan come online, numerous European markets come online, Canada, Australia, et c. I think as the world starts to expand their global reach for adult PCV vaccines, we see the growth of the market coming internationally. But obviously the lion's share of the market in terms of value and volume is coming from the United States. So we will focus on both of those areas. You asked specifically about how we will commercialize.
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-U.S. markets, we will 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 is 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. We are going to keep that option open and continue to think about the strategy. Maybe I will turn it back to Grant for the second part of that question.
Yeah, thanks, Mike. Nick, as it relates to the competition, it has been obviously something we have been laser-focused on as we have been dedicated to this class for some time now. I would just go back to the comments that were made from other sponsors a number of years ago, where it was clear that going beyond 20 or 21 conjugates using the conventional technology did not look practicable. In fact, that is 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 or 21 into a single formulation was not practical.
In the meantime, other efforts to develop PCVs beyond that have fallen away. We had a 21-valent that fell away, a 24-valent that fell away from the competition, a 25-valent that more recently fell away in the adult space. To our knowledge, there are a couple of programs that are in very early development that are talking about 30+. I think there is one in pre-clinical, there is one in phase I development, but there has been no data generated, and these are using novel approaches for which there is no clarity that they are going to be able to deliver something beyond what has been shown to date.
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 make it only that much more difficult to be able to show non-inferiority in the context of a 30+ valent vaccine. We do feel incredibly good about this data, the prospects it has for the potential of VAX-31, and the potential durability of VAX-31 going forward in light of that fact set.
Thank you. As a reminder, to ask a question, you may do so by pressing star one. Additionally, in the interest of time, we ask that you limit yourself to one question. We will go next to Tara Bancroft with TD Cowen. Your line is now open.
Hi, good morning, and really congrats on this fantastic data. My question, I want to go back to what you said, your comments on recommendation from a couple of questions ago. I just want to get your thoughts on the possibility of a preferential recommendation with these data and even if there's the need or desire for that given everything that you've said about the increased coverage anyway. That's just a confirmatory one.
Then some clarity on the timeline to BLA. I know it's quite a ways away, but I'm just wondering, the manufacturing study, that's probably the gating factor for that, right? Mostly trying to see, do you need OPUS-2 and OPUS-3 to file? Do you need the manufacturing study? Basically, 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, we need to be careful, right? We're thrilled with this data. We think it's incredibly clear. Preferential recommendations are not the norm. What we look at is how has the performance of broader spectrum vaccines gone? As we've said time and time again, coverage is king. The broader spectrum vaccines have dominated from a market share perspective. 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 recommendation, then it happens really fast. We saw that with Shingrix. 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 serotypes like serotype IV.
That is not going to be a problem for us, but I can imagine that we would not say anything like that. But we certainly think we have a profile that is superior than having no precedent. So, we appreciate the thought, but I think we've stopped short of that in the context of what we have in this moment. But Andrew, would you want to talk about the BLA question?
Yeah. Tara, to your question on timelines. As you saw, obviously, guiding to the submission of a BLA in the first half of 2028. OPUS-1, as I mentioned, is certainly the cornerstone. In OPUS-2 and OPUS-3, we need the number of subjects exposed across the studies to meet those 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.
The OPUS-2 study in particular should be quite interesting, or OPUS-3, excuse me, as we look at VAX-31 administered to subjects who previously received a less prevalent 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. We've got the OPUS-1, OPUS-2, and OPUS-3 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 comprise the BLA-enabling activities that put us in a position to submit the BLA. But as I said, it is not just about submitting the BLA, it is 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. Rest assured, we will be looking to move as quickly as possible. But 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 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. One question that I had was around the competitive pipeline of 30+ valent PCV. You guys will be at a minimum a couple of years ahead of any of those approaches. Just want to confirm, would your assumption be that VAX-31 would likely be the requisite active comparator with the 0.667 non-inferiority lower bound or margin?
In the past, you guys have talked about the 25% average higher immune responses versus PCV20 on the basis of your prior phase II. I think to convey that there was no trade-down on some of the legacy strains. I think directionally, we can infer that by looking at the plots here, but wondering if you can confirm that even if it's just directional. Thanks.
Yeah. Thanks, Jason. Yeah, as it relates to the 30+ pipeline, yeah, early days, right? To the extent, it's hard to imagine that we wouldn't be in a position to have our product on the market. To the extent our product would be approved, given those precedents that I cited earlier, we would most certainly expect that the comparative product in development would need to be compared to VAX-31.
As we've said publicly in the past, it's our belief that the 0.667 non-inferiority bar is a class-wide FDA position. Yeah, I think that that is very much our expectation, so we believe that we have raised the bar effectively for companies that come along afterward. Yeah, I think that's going to be a very difficult challenge for others and obviously sets us up quite well. Let's see. What was the second question?
The immune response relative to PCV20 and—
Oh, yeah. On a relative basis. Jason, good question. If you look at the average immune responses on the raw data, we're definitely delighted across the board. We're seeing average higher immune responses against each of the comparator vaccines. But 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. 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. We have gotten past the consistent drop across overlapping serotypes, and we have 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 Shrader 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 VAX-24 to VAX-31? Do you have confidence that you are not done? And kind of relevant to that, do you think this world of vaccines might move to the other world of vaccines where you could update? For instance, you could add a little more 12 or something else that breaks out without going through this gigantic process? Thank you.
Well, thank you, Tom. Jim, do you want to take that one?
Yeah. So obviously, you can see that where we ended up with our results for the VAX-31, we believe that there is some incremental headroom. Right now, we are covering the vast majority of circulating serotypes, and adding an incremental serotype or two relative to the gain in coverage, we do not see as specifically a need for that at this time. But this space has evolved over time. There is a phenomenon of serotype replacement where other serotypes have emerged as vaccines were effective. So we are preparing for that, and we believe we will move forward with that if necessary.
Yeah. Tom, I think you're pointing out the phenomena of carrier suppression that has governed this class. We haven't talked a lot about it in the context of today's conversation, but 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 analogy 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've originally expected and not pay a penalty for it.
So we are definitely charting new territory as it relates to how we have moved toward higher doses that have yielded higher immune responses. 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 future expandability to the extent the epidemiology warrants it, and just continues to get us excited about the infant data that'll read out next year.
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 VAX-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 Gould with Cantor. Your line is now open.
Great. Good morning, Grant and team. Let me echo the earlier congratulations. Is there any shift in 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 exceeded your own expectations?
Thank you, Carter. Appreciate that question. I have not checked my email to see if Mike has sent me some new requisitions, but that could come. Mike, how would you answer that question?
Yeah, look, obviously we are thrilled by the data, and that exceeded even our expectations. We are really excited. I think that the plan of attack is still the same. This is a really concentrated market, Carter. It is, I hate to say straightforward because it is super complicated of course, but we will spend our time focused on the retail pharmacy segment and large health institutions. It all starts today with making sure that these data are clear, making sure that 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 built quickly.
Yes, of course, the requisitions will be coming to Grant very quickly. But we are ready and feel like we are in a really great position, and I think feedback so far from all of you has been really great, and we will hear from the scientific community over the course of the next few weeks that we are looking forward to.
That is good.
Thanks, Carter.
Thank you. Our final question today comes from Joseph Stringer with Needham and Company. Your line is now open.
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 one or more of those adult growth drivers be supercharged? Could it kind of drive the adult market growth even higher than expected in the total market over that 2030 to $12 billion estimate? Thanks.
Yeah. It's a good question, Joey. I'll let Mike chime in in a second. But 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.
The conversation very specifically focused on the high valent vaccines coming with specific reference to VAX-31. 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. Yeah, I think it certainly directionally will be valuable. Yeah, that's my first reaction. But Mike, how do you think about it?
Yeah, I think it starts certainly with recommendations. If we think about the U.S. first and then maybe I'll talk about OUS, Joey, but U.S. first, as Grant said, there's been this conversation about when will the booster dose be necessary. I'll also offer that the recommending bodies, ACIP or other, will certainly consider the need to revaccinate previously immunized adults with PCV13 or PCV20 or PCV21 or PPSV23. I think that the recommendation there can obviously substantially increase the size of the market. Also, I think importantly today in the United States, the aged 50 to 64 category has a lower immunization rate than the 65+ category.
To the extent that 50- 64 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.
Most of the recommendations are 65+ . Those catch-up immunizations are starting to occur, but the speed of those ex-U.S. could be very helpful to the market size. Do the recommending bodies in other countries move down to the 50- 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 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. Well, we can conclude today's call. I do want to just thank not only the study participants, investigators, and everyone at Vaxcyte who I referenced earlier, but I also want to acknowledge the investors who have supported our efforts to date, 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, and we really appreciate your support.
Thank you for joining today's conference call. This concludes the call. You may now disconnect.