Moderna, Inc.

Standing by, welcome to the Moderna Second Quarter 2026 conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you'll need to press star 1-1 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 1-1 again. Please be advised, today's conference is being recorded. I would now like to hand the conference over to your speaker today, Lavina Talukdar. Please go ahead.

Thank you, Kevin. Good morning, everyone. And thank you for joining us on today's call to discuss Moderna's second quarter 2026 financial results and business updates. You can access the press release issued this morning as well as the slides that we'll be reviewing by going to the investor section of our website. On today's call are Stéphane Bancel, our chief executive officer, Stephen Hoge, our president, Jamie Mock, our chief Financial Officer, and David Berman, our Chief Development Officer. Before we begin, please note that this conference call will include forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Please see slide two of the accompanying presentation and our SEC filings for important risk factors that could cause our actual performance and results to differ materially from those expressed or implied in these forward-looking statements. With that, I will now turn the call over to Stéphane.

Thank you, Lavina. Good morning or good afternoon, everyone. Thank you for joining us. After my review of the second quarter, Jamie will present our financial results and outlook, followed by Stephen with recent business updates. Then David will review our clinical progress in oncology and Rare Diseases. And then I will close by discussing our key value drivers. As you know, the second quarter is always light for seasonal vaccines. We generated revenue of $0.1 billion, which exceeded the top of our range. Our focus on financial discipline continued. We reduced cash costs by 10% in Q2 compared to the second quarter of 2025. We reported a net loss of $0.8 billion. We ended the quarter with $6.9 billion in cash and investments, maintaining a strong balance sheet while continuing to invest in our pipeline. Overall, I am pleased with our continued execution across the business. This team has done a great job to get us ready for the 26-27 vaccination season and our pipeline is progressing well. During the quarter, we delivered several important updates across our pipeline. In our respiratory portfolio, Our seasonal flu vaccine, mRNA-1010, received a positive recommendation from the US ViyaPak. This represents another important milestone ahead of our August 5th PDUFA date and brings us one step closer to potentially making our flu vaccine available to patients. For our norovirus vaccine, mRNA-1403, following an interim analysis, we are preparing to enroll an additional cohort in its phase 3 trial. In oncology, we are very pleased to present the five-year phase two update of intesmoron autogen in combination with Ketudra in adjuvant melanoma at ASCO 2026, highlighting the continued durability of a clinical benefit observed of this program. We also presented important translation data that provides additional confidence in the mechanism of action over individualized new antigen therapy. And finally, we're excited to announce that dosing has begun in two cancer antigen therapy programs, the Phase 1-2 study of mRNA-4194 in Lynch syndrome and the Phase 1 study of mRNA-4200 in solid tumors. Beyond our pipeline, we also had several notable corporate achievements during the quarter. We are pleased to expand our partnership with CEPI to explore the development of an Ebola vaccine reinforcing our long-standing commitment to global health security and pandemic preparedness. We were also honored to be named the world's most impactful company by Time magazine, recognizing our pioneering work in mRNA science. This recognition reflects both the global impact we made during the pandemic and our continued effort to advance a broad pipeline of innovative medicine and expand access to mRNA technology worldwide. Turning now to our leadership team, I'd like to highlight two important appointments we announced this quarter. As we continue to strengthen Moderna for the next phase of growth, I am very pleased to welcome Esther Bank as our new Chief Commercial Officer. Esther joined us with more than 30 years of commercial leadership experience and an outstanding track record of leading high-performing organizations across the healthcare industry. More recently, she led U.S. operations at Zoetis and before that at several commercial leadership roles at BMS and Novartis, where she helped bring important medicines to patients around the world. Esther now leads a global commercial organization as we prepare for multiple launches and continue expanding into new markets. We are delighted to have Esther John Moderna and have been enjoying working closely with her. I am also pleased to welcome Michael McDonald to Moderna's Board of Directors. Michael is familiar to many of you, as most recently he served as Executive Vice President and Chief Financial Officer of Biogen. Michael brings more than two decades of public company CFO experience and deep expertise across finance, capital markets, investor relations, and corporate governance. His experience across the life science and technology sectors will be a valuable addition to our board as we continue to execute our strategy and create long-term value. We are delighted to welcome Michael to Moderna's board. With that, I will now talk to Jamie.

Thanks, Stéphane, and hello, everyone. Today I'll start with our second quarter financial results and then review our updated financial framework for 2026. Let me start with our commercial performance. For the second quarter, total revenue was $145 million, above the guidance range we provided on the first quarter call. Our geographic mix for the quarter was 60% U.S. and 40% international. For the first half of the year, total revenue was $0.5 billion. with 31% from the US and 69% from international markets. Our long-term strategic partnerships drove the strong international contribution during the first half. Overall, we are pleased with our first half performance and are reiterating our expectation for revenue growth of up to 10% in 2026. We continue to expect a roughly 50-50 split between US and international revenue for the full year. and we expect third quarter revenue will represent approximately 55% of our second half revenue. Now let me turn to our second quarter financial performance on slide 10. As I just mentioned, revenue was $145 million in the quarter, up 2% from the prior year. Cost of sales for the quarter was $93 million, a 22% decrease compared to the prior year, primarily driven by lower unutilized manufacturing capacity costs, as we continue to improve our manufacturing efficiency. R&D expenses for the quarter were $651 million, a 7% decrease compared to last year. The decline was driven by lower clinical development costs following the wind down of several late stage programs. SG&A expenses for the quarter were $216 million, down 6% from last year, reflecting continued cost discipline across the organization. Our income tax provision was immaterial in both periods as we continue to maintain a global valuation allowance, which limits our ability to recognize tax benefits from losses. Net loss for the quarter was $782 million, improving by $43 million, or 5% compared to last year. Loss per share was $1.97 for the quarter compared to $2.13 last year. We ended the quarter with cash and investments of $6.9 billion compared to $7.5 billion at the end of the first quarter. The decrease primarily reflected cash used to fund operations as we continued to invest in R&D and advance our pipeline. In July, we paid $950 million related to the litigation settlement announced earlier this year, which will be reflected in our third quarter cash balance. Now let's turn to our financial framework for 2026. We still expect total revenue to grow up to 10% in 2026 with the geographic mix and quarterly phasing I previously mentioned. Our 2026 revenue guidance factors in potential future declines in COVID vaccination rates and continues to assume no revenue from M. flusiva and M. cambriax. We are lowering our cost of sales projection by $0.1 billion to $1.7 billion, reflecting additional manufacturing efficiency gains. The $1.7 billion estimate includes $0.9 billion of expense related to the previously announced litigation settlement charge. We are also lowering our R&D expense estimate by $0.1 billion to $2.9 billion due to operational efficiencies. SG&A expenses are still expected to be approximately $1 billion flat versus the prior year. Similar to 2025, our commercial spend will be more heavily weighted to the second half of the year due to the seasonality of our business. In aggregate, excluding the $0.9 billion litigation charge, we are expecting total gap operating expenses of $4.7 billion and $4 billion of cash costs. which exclude stock-based compensation, depreciation, and amortization. Each reflects a $0.2 billion improvement compared to our previous guidance. We expect taxes to be negligible in 2026. Capital expenditures are still projected to be between $0.2 and $0.3 billion. Cash and investments are now projected to be between $4.7 and $5.2 billion at the end of 2026 which reflect the improvement in our cash cost guidance. As a reminder, our cash guidance does not assume any additional drawdown from our remaining $0.9 billion undrawn credit facility. With that, I will now turn the call over to Stephen.

Thank you, Jamie, and good morning or good afternoon, everyone. Today, I'll take you through our recent business updates. Slide 13 outlines our multi-year revenue growth strategy. Anchored in geographic expansion and portfolio expansion from the continued advancement of our product pipeline. For 2026, we continue to expect revenue growth of up to 10%, driven by our long-term strategic partnerships in the United Kingdom, Canada, and Australia, and supported by the continued growth of MNEX Spike. Looking across the three-year horizon, we are building toward a broader and more diversified portfolio, including flu, Our combination flu and COVID vaccine and norovirus, as well as late-stage programs in oncology and rare disease, while continuing to expand our global commercial footprint. We're making tangible progress against this strategy, and NextBike is now approved in Japan and Taiwan. Our flu program received a unanimous recommendation from the VRBPAC FDA Advisory Committee. and we signed a joint procurement contract with the European Commission for up to 24 million doses of MResvia across six countries. We also received approval for MResvia in Mexico and a label expansion for the product in Australia. In Latin America, we advanced our strategic partnership in Brazil by signing an agreement with a local manufacturer to support our multi-year COVID vaccine supply agreement with the government. Finally, as our commercial portfolio expands, Emerging real-world evidence strengthens the support for our respiratory portfolio. Slide 14 highlights our approved infectious disease portfolio and several recent updates across the products. Starting with COVID, health authorities in the United States and Europe have selected the XFG strain for the 26-27 season, and we are updating both SpikeVax and MNEX Spike to target this strain for the upcoming vaccination season. For spike facts, we also recently published a real-world evidence study. A link to the study is included on this slide. And NexSpike is now approved in the United States, Europe, Canada, Australia, and as mentioned earlier, now in Japan and Taiwan. Additional filings are planned for the second half of 2026. We also published a real-world evidence study evaluating the adjusted vaccine effectiveness against COVID-related hospitalization during the most recent 2025-2026 season, which I will discuss in more detail shortly. Turning to MRESVIA, which is approved in 44 countries, most recently it was approved in Mexico for all adults age 60 and older as well as high-risk adults age 18 to 59. We also received a label expansion in Australia to include high-risk adults age 18 to 59. In addition, A real-world evidence study evaluating vaccine effectiveness against hospitalization and associated with RSV-related acute respiratory illness was published for mResvia. Finally, mCombrax is now approved in the European Union and is under review in Canada, Australia, and most recently, Japan. In the United States, we are awaiting approval of our standalone flu vaccine before seeking further guidance from the FDA on next steps for refiling the combo here. Slide 15 highlights the emerging real-world evidence supporting MnexBike's clinical profile. As a reminder, during its first season on the market in 2025-2026, MnexBike captured approximately 24% of the total U.S. retail COVID vaccine market. Uptake was particularly strong among older adults, with MnexBike accounting for approximately 34% of the retail market among individuals age 65 and older. This market uptake was supported in part by the Phase III head-to-head data of MNIC spike versus spike facts. The subsequent real-world analysis evaluated adjusted vaccine effectiveness against hospitalization with documented COVID-19 during the 2025-2026 season. Among adults age 65 and older, vaccine effectiveness was approximately 59% for MNIC spike compared with a matched a matched unvaccinated cohort. Among adults age 75 and older, it was approximately 67%. These estimates were numerically higher than those observed for a competitor vaccine and separately matched analysis. While this real-world study was not designed as a head-to-head comparison, the numerical differences are encouraging, particularly when considered alongside the vaccine efficacy observed for MNIC spike versus spike facts in the Phase 3 head-to-head trial. Taken together, the strong initial market uptake and the emerging real-world evidence highlight MNIC spike's potential, particularly among older adults. Turning now to our late-stage infectious disease pipeline, starting with flu, we are grateful for the unanimous VRBPAC recommendation for mRNA 1010 and look forward to the potential for approval with the PDUFA date of August 5th in the United States. mRNA 1010 is also under review in the European Union, Canada, and Australia. The efficacy and safety results from our Phase 3 study were recently published in the New England Journal of Medicine. A link to the publication is included at the bottom of the slide. For our norovirus vaccine, mRNA-1403, the Phase 3 study did not meet the statistical criteria for early success at its interim analysis. The study remains blinded as we now prepare to enroll an additional fourth cohort. With that, I will now turn the call over to David who will provide a more detailed update on our oncology and rare disease pipelines.

Thank you, Stephen. Before I begin the review of our oncology and rare disease pipeline, I want to take a moment to say how excited I am to be here. Before joining Moderna, I followed the company's oncology portfolio and in Tismoran in particular very closely. The strength and potential of the pipeline were an important part of what attracted me to the Chief Development Officer role. Since joining the company and spending time with the teams, I have become even more impressed by the quality of the science, the depth of the programs, and the opportunities ahead of us. With that, let me take you through the progress we are making across our oncology and rare disease pipeline. Starting with Imtysmoran, our individualized cancer therapy developed in partnership with Merck, The program continues to advance across a broad portfolio of nine Phase II and Phase III studies. In adjuvant melanoma, the Phase III study is fully enrolled, and we look forward to the interim analysis in 2026. At ASCO, we presented the five-year update from the Phase II study of Entismoran in combination with Keytruda in the adjuvant melanoma setting, as well as translational data demonstrating the induction of de novo neoantigen-specific T cells following treatment. A link to our ASCO investor event presentation is on the bottom of this slide. Our phase three development program also includes studies in adjuvant non-small cell lung cancer, including a phase three study in patients without a pathologic complete response following neoadjuvant therapy, as well as the recently initiated stage one study evaluating in Tismoran both as monotherapy and in combination with Keytruda Q-Lex. Across the phase two portfolio, the adjuvant renal cell carcinoma and muscle invasive bladder cancer studies are fully enrolled and continue to accrue events. We are often asked when we expect these studies to read out. Because both studies are event driven, It is difficult to predict the timing with precision. The renal cell carcinoma study has been fully enrolled since the second quarter of 2025, so it is possible that the threshold for the analysis could be reached this year. However, it is also possible that this occurs next year. It depends on the pace of event accrual. The muscle invasive bladder cancer study completed enrollment earlier this year. and we currently expect the readout to be more likely in 2027. Again, subject to the timing of event accrual. Non-muscle invasive bladder cancer study continues to enroll. As a reminder, this trial is evaluating both in Tismoran with BCG in combination as well as in Tismoran monotherapy. Beyond the late stage portfolio, our phase one studies in adjuvant pancreatic cancer and perioperative gastric cancer are also fully enrolled. And we look forward to sharing data from these programs as they mature. Taken together, the breadth and continued execution across the Entismoran program reflect our commitment to evaluating this therapy across multiple tumor types and stages of disease. Outside of Entismoran, We continue to advance a broad portfolio of oncology programs across cancer antigen therapies, T-cell engages, and cell therapy enhancements. mRNA-4359 is in a Phase II program in first-line metastatic melanoma and second-line, or later, metastatic melanoma. It is also being evaluated in first-line metastatic non-small cell lung cancer. We are also advancing two additional cancer antigen therapies. MRNA 4106 and MRNA 4200 in a Phase I study in patients with advanced solid tumors. I am pleased to report that dosing has now begun with MRNA 4200 alongside the ongoing evaluation of MRNA 4106. In addition, MRNA 4194 has entered clinical development with dosing now underway in a Phase I-II study in individuals with Lynch Syndrome. This program is designed to evaluate the potential of our technology in an earlier cancer interception setting. Our T cell engager, mRNA-2808, also continues to advance in a Phase 1-2 study in multiple myeloma with patients actively dosing. Finally, in collaboration with Ematics, dosing continues in the Phase 1 study of mRNA 4203 in combination with the Anzu cell therapy. These programs demonstrate the breadth of our oncology pipeline and the continued progress we are making across several distinct therapeutic approaches. Moving now to slide 20, in rare diseases, our propionic acidemia, or PA program, is fully enrolled in its registrational study, and we expect data from the study in 2026. For our methylmalonic acidemia, or MMA program, as mentioned last quarter, we have deferred our decision on a pivotal trial until the PA readout. With this review, I will now hand it over to Stéphane.

Thank you, David, Stephen, and Jamie. Looking at the second half of the year, on the commercial and financial side, We remain on track for up to 10% revenue growth this year and also remain committed to improving our operational efficiency and achieving our new, lowered cash cost guidance of approximately $4 billion. We also expect to build on last year's success MRM's Next Spike launch and to continue expanding across the COVID patients around the world. We look forward to approvals for MCOMP REACT in Canada and Japan. and following the positive recommendation from the U.S. VRPAC, we now look forward to the August 5th P2FA date and potential approval of our seasonal flu vaccine in the U.S. We also anticipate approval for flu in Canada and Europe. From a pipeline perspective, oncology remains a key focus with important milestones ahead for entismoron in multiple tumor types. As David said, our research and study in PA will expect data this year. We have a busy second half of the year ahead of us. Success will come from disciplined execution across our key priorities, and I'm confident in our team's ability to deliver. We will be happy to host you in Cambridge or online for Analyst Day on November 12th. Finally, I would like to thank our employees around the world for their continued commitment to our mission and for everything they have accomplished this quarter. With that, operators will be happy to take questions.

Thank you, ladies and gentlemen. If you have a question or a comment at this time, please press star 1-1 on your telephone. If your question has been answered, you wish to move yourself from the queue, please press star 1-1 again. We'll pause for a moment while we compile our Q&A roster. Our first question comes from Salveen Richter with Goldman Sachs. Your line is open.

Good morning. Thanks for taking my question. Two questions for me. One is in the case that the Phase III in Tis Moran melanoma study passes the first interim and progresses to a second and or final analysis, how should we interpret that in the context of powering an event accrual and how detailed will your disclosure be? And the second question for me is if the trial is indeed positive here, How do we think about read-through to other tumor types like lung in the context of tumor and mutational burden, but also the fact that you're talking about different neoantigens that play the key role there as you think about the cassette? Thank you.

Thank you very much. A lot of questions in there. I think with regard to your first question, if the Phase III INT study in melanoma continues, You know, it continues. We haven't disclosed the statistical powering or the thresholds for early interim efficacy, so I think I won't really address any more about that. With regard to the press release, I think it's too early. Let's see what the data is, and then we'll figure out what exactly the wording will be in the press release. I think with your other question, if Entismoran is positive, what's the read-through? I think it's a very important question, one I've given a lot of thought to. I think there are several important things we need to see here. One is, you know, what is the degree of efficacy that we see? Number two, are we confident that the mechanism that we see can be validated? And I think with regard to that, the data that we've shown at ASCO confirms that when we give the neoantigen vaccine, we do see neoantigen-specific T cells, and we know those T cells can kill the tumor. So I think I think that we have moved to other tumors where checkpoints do work, and we know that this mechanism that I just talked about is the mechanism by which other checkpoints do work. And so since checkpoints work in lung cancer and bladder, I think that gives us increased reason to believe in bladder. I think the big question comes out in tumors where checkpoints don't work, and that's pancreatic cancer and to a lesser degree gastric. So that's why we're conducting Phase II trials and Phase I expanded trials and those other tumors.

And, Salvin, maybe on your first question, just to fill in a little bit, as David said, we haven't disclosed the statistical analysis plan, but suffice it to say it's an interim analysis and there are still subsequent planned analyses. And ourselves with our partner, Merck, designed the overall study to evaluate, you know, the full commercial profile of the product. And so we do think that there's a commercially valuable product that could emerge maybe only in the final analysis, but that wouldn't meet the criteria for early efficacy at the interim. And obviously, we'll move forward with the study accruing events to characterize that, but we do still see there is an opportunity there.

Thank you.

One moment for our next question. Our next question comes from Tyler Van Buren with TD Cal, and your line is open.

Hey, guys. Good morning. Thanks for all the updates. Another one on the Phase III melanoma INT readout. Forgive me, but I have to ask for more granularity on timing. You know, how close are you to achieving all the events required for the first analysis? What percentage of events for the first analysis have been observed? And what's your level of confidence that we'll get the data readout this year?

Tyler, hi. Good to hear from you. So we're not going to disclose any more details around the Thank you very much. Thank you.

If it succeeds in the phase three, do you expect standard review or is a priority review possible? And can you remind us what your capacity to treat patients would be on approval?

So, priority review will always be subject to the data, but we certainly hope, certainly if we're successful, that it will be under consideration and then an accelerated review process is possible. You know, as David said, we are We're highly confident we'll get that data in the second half of this year, or at least that interim analysis will be conducted. And if that is positive, again, we don't have the data yet, then we would obviously make the case for an accelerated review. And we think it'd be supported by any profile that looked like the phase two. Now, as to commercial capabilities, we have been Establishing the manufacturing in Massachusetts in a dedicated facility that will be able to support launch. We believe that facility can support our commercial profile that ourselves and our partner Merck have articulated for several years to come. We hope we have to build more in the future if there's more demand, if all goes well. But we do believe we can satisfy the initial indication out of that facility and that we'd be ready to go next year if all went perfectly to plan.

Thank you. One moment for our next question. Our next question comes from Ellie Murrell with Barclays. Your line is open.

Hey, guys. Thanks for taking the question. Just two for me, one on flu and then one on INT. Just in terms of flu, I guess curious if you've had any discussions with the FDA regarding strain selection for 2027, specifically if there's a mismatch in the selected strains in the beginning of the year with the circulating strains later in the year, would you be able to update your strains, whereas the other flu vaccines wouldn't be able to? Basically, just curious if This came up at all in the discussions and how you're thinking about this as a potential possibility in 2027. And then just a second question, INT, interesting analysis on the immunogenicity that you presented at ASCO. Curious if there's any learnings in terms of how you think about the algorithm for the Thank you for both questions. So I'll take the flu one and obviously have David take INT.

So first, in terms of discussions with US FDA, the answer is yes, those have happened. In fact, they even happened at the advisory committee, and so there was active discussion both between the agency, the committee members, as well as the company on how we would address a potential mismatch or a late strain selection. Our demonstrated capability in the COVID context is less than two months, and so strain selections have happened as late as early July in the history of COVID. and we've been able to make a fall vaccination season work with millions of doses. And that was discussed at the VRBPAC and obviously had been part of the basis for pursuing accelerated approval in our discussions with the agency. Now the process by which that would happen would ultimately fall to public health to articulate. And so FDA, CDC, WHO, others would need to accommodate a late strain selection if they wanted to. and those discussions I would describe as in their early stage. The first step is to get the product approved so that there's a potential to address such a situation and then the second step was to work closely with public health to define how we would do that and under what circumstances they would want us to do that.

Ellie, with regard to your second question, It's a very interesting question. So we see that about 29% of our neoantigens that go into our cassettes in general are immunogenic. And the data that we showed is that for the patients that we showed, there were between 1 to 18 neoantigens that were reactive in each patient. So the good news is you only need one neoantigen reactive T cell in order for there to be activity. of course, the more, in theory at least, the more the better. In terms of what we're doing to improve, we do have an ongoing program to try and improve this algorithm. In fact, we're using artificial intelligence to try to develop the next algorithm. I think the key thing will be when we get an efficacy readout linking our algorithm to efficacy, I think that will be the next important step here.

Great, thanks.

One moment for our next question. Our next question comes from Terrence Flynn with Morgan Stanley. Your line is open.

Great. Thanks for taking the questions. Maybe just on your flu vaccine, I was wondering if you could provide any update in terms of your thoughts on potential pricing, either some of the inputs or how you're thinking about analogs there. And then on the Norovirus Interim, just any insight in terms of what that means for potential effect size. Thank you very much.

Great. Thank you for both questions. So first on flu pricing, look, it's a little premature. Those conversations are ongoing, but it's all subject to us getting the product approved, obviously. When we think about the positioning of that product, at least on our own with the data, we feel confident about that profile given the relative vaccine efficacy demonstrated in the phase three trials and published in the New England Journal relative to standard dose that it really is in the enhanced category from our perspective and importantly offers some features for instance the lack of egg adaptation that are even more specialized than some of the available therapies and so we will be assessing from a health economic perspective the potential value of those and in discussions with payers and other bodies, making sure that we characterize those potential benefits as we think about pricing in the future. But again, first step is let's get the product approved, which we're working on right now. As it relates to norovirus, there will not be much more I can say than what we have right now because we are still, the study is blinded and continuing. We have not previously disclosed the statistical analysis plan associated with it, so it would be inappropriate to do that now. Suffice it to say, what we are doing is we know we will need additional cases from a further cohort to strengthen that statistical analysis, and we're working hard on preparing to stand up that part of the study now.

Thank you. One moment for our next question. Our next question comes from Corey Kasloff with Evercore ISI. Your line is open.

Hey, good morning, guys. Thanks for taking the question. Wanted to also ask on Entismoran, but on the RCC front, can you speak to the immunogenicity data that you have that kind of gives you confidence that Entismoran works as well in low TMV RCC as what you've seen so far in melanoma and non-small cell lung cancer? Thank you.

So that trial is still ongoing, so we don't actually have that data yet, but we We will be showing some data later this year on other tumors that are hard to treat. And I think the fact that we can demonstrate immunogenicity in, for example, pancreatic cancer, I think leads us to believe that we can identify neoantigens and create a neoantigen vaccine for RCC as well. I think we have confidence in that.

And I think the one thing I'd add is at least in the context of our phase two melanoma study, which is now through five years, we had previously published or presented that TMB did not correlate with a difference. In fact, low TMB adjuvant melanoma patients had a consistent hazard ratio as those with high. So it gives us some reason to believe that that will translate. But to be fair, that is in the melanoma context. And as David said, we're still waiting for data in other histologies.

Yeah, and I guess just to be clear, I was wondering that kind of where the confidence came from recognizing, you know, we're waiting on that data later this year or next.

Yeah, and I think it comes from the lack of a role of TMB high versus low in driving the effect size that we saw in the phase two and the totality of data we have around that. Got it. Thank you.

One moment for our next question. Our next question comes from Andrew Sauer. Jeffrey, your line is open.

Hey, good morning. Thanks for taking my question. So just thinking about your, quote unquote, horizon two wave of assets coming, first for the Ido compound, sounds like that could have pivotal data in 2027 since you mentioned it as a revenue contributor in 2028. So can you talk about what the approvable bar in first line, second line melanoma is? And then you also have a TESOL engager program that you announced at the Science Day that I believe could have data year-end. And so I'd be curious to know, in a seemingly refractory population, what would a positive data look like in myeloma, and is there a strategy for you to go upstream? Thank you.

Thank you, Andrew. So Horizon 2, I'm glad you picked up on that. 4359, which is the ideal PD-L1, is a very interesting program. There was proof of confidence from a randomized study from another company, which was very interesting. For us, we saw very intriguing data, which we showed last year, and we had a follow-up first-line data set earlier this year. What we're doing now in the expanded, in the ongoing Phase 2 expansion is to confirm that signal. Is the signal that we saw real, and is there a path forward based on that signal? And I think, I don't want to get ahead of whether it's pivotal or not. I think let's first confirm the signal and identify what is the best opportunity in melanoma. Is it to go first line or is it to go second line plus? I think as we all know, the bar in terms of your question about what is the bar for approval in second line for single arm trials, you know, it's a moving target as we see. I think suffice it to say that you have to show sufficiently high response rates that have sufficient durability. And I think no one really exactly knows what that definition of sufficiently high is. In terms of first line, we do have an ongoing combination with NEVO IPI. We showed data earlier with PEMBRO plus 4359, which was very intriguing. But we have to remember also that in single arm trials, especially in the first line setting, the combination of two active agents may sometimes be hard to disentangle what the activity is through. So we're looking for, can you safely combine them in first line? Do we see some signal of increased activity? and in second line in the PD-1 relapsed refractory, we're looking, do we see sufficiently increased signal of activity above what we would expect to see? And in particular, in patients who progressed on prior PD-1s, are we seeing durable responses? So more to come on that next year. With regard to 2808, which is the T-cell engager program, this is something that's very interesting. So multiple myeloma obviously has a number of T-cell engagers and we recently heard this week from J&J, very exciting news about the first combination of two targets. That's the first time ever two T-cell engagers have been combined. And so for us, the reason we're excited is we have the first three T-cell engagers in a single product ever being studied. And as you mentioned, we're setting this in relapsed refractory myeloma in patients who've progressed on multiple CAR Ts, on multiple T-cell engagers, essentially patients who have no other options available And so we're going to be looking, first of all, can we produce three T cell engages, number one? Is it safe and well-tolerated, number two? And is there evidence of complete responses and partial responses and how durable they are? That's, I think, what we're looking for. But I'm quite intrigued and excited about both of these programs. Thank you.

One moment for our next question. Our next question comes from Courtney Breen with Bernstein. Your line is open.

Thank you so much for taking the question this morning. Just a couple of others, one to push a little bit further on. Norovirus and the update there. Obviously, the question that I think many of us are asking is, is this enrollment? Is this an efficacy or is this an events situation? And so perhaps if you can help us understand kind of the overall event rate relative to expectations and what might be driving that. And then the second question is a little different. You obviously just announced a new chief commercial officer into the company, and you've obviously got kind of a broadening business, particularly as we look at the pipeline and the number of readouts over the next couple of years. Can you just help us understand what are the top priorities for the chief commercial officer over the next six months, and what might be the changes or the evolution required longer term in the commercial structure to support this evolving business?

Thank you. I'll take the first question and obviously turn it over to Stéphane to handle the second. First on the question of Noro, again, limited in what I can say because the trial remains blinded, but it's suffice to say we are going forward with another season this year. We have been able to enroll the trial, which I think was your question, the cohort's But the epidemiology of the primary endpoint cases has been a little bit slower coming. As we had previously discussed, some of that in the first season for that trial was the result of a unique outbreak of a different set of strains of norovirus that were not contributing to that primary endpoint. And so cases came a little bit slower in that season. And for that reason, we were a little bit slower to achieve the interim analysis than we intended. We ultimately did, though, power the study for a final analysis, a full number of cases. And really what we're doing now is we've kind of gone through that second season, been able to conduct the interim analysis, is we're preparing for that third, which will be the third winter this year. This has happened with other vaccines in the past. If you think about flu vaccines, they often have to do multiple season studies to accrue sufficient cases and did ultimately happen to us here, or at least appears to have happened to us here. And so for that reason, we're getting ready to stand up that new case accrual. It's unique in that we have to enroll new patients to get new cases because it's a seasonal vaccine, a seasonal vaccine. Thank you, Stephen.

Good morning, Courtney. So, in terms of context, as we talked about in the press release when we announced the position of Esther, basically, if you look at the business, as you know, we have three products on the market today. We have, since the spring, a fourth product approved in Cambriax. The FooCovid combo, which we are preparing the launch for 2027. Potentially a fifth product approved in H2, which of course flew, as we talked about before. So as you can see, just what is just in front of us is a very, very large growing ID pipeline of product. And the other piece also, as you know, is Europe. As you know, we have not been able to participate in the European market because of an exclusive partnership that the EU has set up during the pandemic. But this potentially expires, as we've said before, in 2026. So we really see Europe as a very important growth driver for us. And as you know, in Europe, the markets are all very, very different. So there's a lot of complexity there. And then, of course, there is INT. As we said, we expect the phase three data potentially in the second half of a year, given the trend. And so, as you can imagine, Moderna and their Merck colleagues have been very active Stephen talked about manufacturing a minute ago, but they've been very active on the commercial side of the house in terms of medical affairs, marketing, commercial. And so that's another piece where AST is also going to be helping and leading working hand-in-hand with Merck. And of course, there's also rare disease with PA. As you know, we've said PA because it's a time-driven phase three. We should have a data this year. Of course, its partners will record that here, but we're going to be, of course, working with a partner to ensure a great launch. So if you look at the next few years, Stephen had a good slide earlier in the presentation looking at the geographic expansion, including also in Asia and Latin America, the product expansion. So there's a lot to do. And so as we are gearing for the growth stage of a company coming ahead of us, we thought that this role was important. And also the new role for Stephen, who is really overseeing ID, INT, and RARE from a kind of general management to make sure that all the functions are integrated together. So it's just us getting ready for the next stage of a group of companies, I think.

Thank you. One moment for our next question. Our next question comes from Michael Yee with UBS. Your line is open.

Thanks. We have two questions. First is on INT for David or Stephen. At the interim analysis, while you're not going to disclose the powering, if you go back to your Phase 2b, it was statistically significant, but you were using a one-sided alpha of 0.1. And so that's a much different hurdle rate than, say, traditional interims that you might be using here. So to what extent that people have too high of expectations for the interim versus the final, where you could have a non-proportional hazard ratio, where the effect size gets better over time, Thank you. Hey, Michael. I'll take the first question.

We're not going to disclose anything on the statistical analysis plan, but I do think there is maybe two key points to highlight. The first is, if you remember back to the Phase 2 study, of course updated at ASCA, there was, as you said, somewhat of a non-proportional hazard with about 12 months for really strong separation to occur. The good news in the Phase 3 study, which was designed with Merck, who has a lot of expertise in melanoma, is that it's requires also a minimum of 18 months follow-up. And so every patient has been followed way beyond where there was before, after the separation occurred. So I think that with regard to that, that gives us increased confidence. Stephen, the second question?

Yeah. On the question of combo in Europe and negotiations, So with approval, we can start the pricing negotiations with many governments where that is a separate process. And so in most cases, we have then submitted those HTA documents as health technology assessments or the supporting pricing negotiations are underway. In some cases, you need recommending bodies, sort of analogous to CDC, recommending body recommendations before you engage in that process. And in all those cases, we've been supporting those. Some of that has been happening publicly, and so you'll see recommending bodies in countries like Germany, where Stieke or others have begun to contemplate the combo vaccine. And then, as I said, in other countries, we've begun that pricing negotiations. There are first instances of pricing being issued in a couple of countries, and we'll continue that process through this year. Once that's there, we will have achieved market access and then we begin the process of engaging in tenders or in countries that are not tender countries in Europe in commercialization and straightforward commercialization. About half of those markets will be more tender related. Some of those tenders will deal with 2027. Some of those tenders will deal with 2028 because the timing of their flu or COVID tenders or maybe a year forward. And we'll provide more clarity on that as we get into that year. So we would expect some contribution from traditional commercialization markets as well as tender markets beginning in 2027, but the full effect really probably not felt until 2028 and maybe a little bit beyond, depending upon what individual countries require from real world effectiveness data or other things post-approval to support market access. So we're excited to be approved. Thank you, guys.

Our next question comes from Jeff Meacham with Citigroup. Your line is open.

Great. Hey, guys. Thanks for the question. I just have a couple of quick ones. I guess for Jamie, the 10% revenue growth guidance for the balance of the year, maybe just give us a reminder of the puts and takes. of that when it comes to different geographies. Are there still more contracts or more sources of potential new pockets of demand? And then on the rare disease portfolio, you guys have completed enrollment in 39-27. Just wanted to get a sense for what determines the timing, maybe the regulatory usability. I wasn't sure what you guys are looking for from an effect size or from a clinical meaningful standpoint. Thank you.

Yeah, thanks, Jeff, for the question. I'll take the first one on revenue. So we're, you know, sitting pretty good after the first half year in terms of a half a billion dollars in revenue. Roughly 70% international, 30% in the U.S. And your question is getting at where's the upside, where's the variables to the second half. So I just want to start by saying, if you look at our first half, we are up almost $300 million versus the prior year. So if we are flat in the second half, that would actually be above 10% growth for the year. So now what are the variables to the second half? If you look at what we said is we're basically 50-50 for the entire year, U.S. versus international. So obviously having a higher percentage in the first half international, that means we have a higher percentage in the U.S. And that's really where the biggest variable is. So across the globe, we've basically contracted. We have to execute. There are some countries that have minor vaccination rate. You know, some shipments could happen in the year or some could go into the first quarter of the following year. But I would call that relatively small. I think the biggest variable comes down to the U.S. And we've provided for, as I mentioned in my prepared remarks, that we have provided for a vaccination rate decline, particularly in the U.S. And so The biggest upside swing is if it is not as big a decline as we've projected, then we should have upside in the U.S. If it's worse than we projected, then obviously there would be downside to that. And so if you just kind of think about the second half in terms of broad pictures, and I kind of said this on the last call, is in the second half international, last year we had no U.K. volume and not some of the strategic partnerships volumes. This year, we will supply some of the strategic partnerships that we have, and it's quite material. And that's basically the upside that is offsetting the provision that we put in to the U.S. in terms of vaccination rate decline. So for the most part, we're really confident we've got a substantial growth through the first half here. If we are flat to last year with international growing and offsetting the U.S. decline, then we should be above our 10% guidance. And the biggest variable at this point is just what is the size of the U.S. market.

Thank you. With regard to the question on PA, it's around 20 patients were enrolled, and the primary endpoint, which is metabolic decompensation events on treatment relative to pretreatment, so each patient serves as their own control, is based on a 12-month follow-up. And so that should happen sometime in fourth quarter. And just as a reminder, in our prior releases, we showed about a 60% to 80% efficacy rate. with our therapy. And so that's why we have confidence or hope for this trial.

I agree. Thanks, guys. One moment for our next question. Our next question comes from Miles Minter with William Blair. Your line is open.

Hi. Thanks, everyone. Congrats on the call-ups. My question is just one on clarification. I think Dr. Colino at ASCO mentioned in Interpath 001 that approximately two-thirds of patients would have micrometastatic disease. It's a little bit confusing to me as to whether that was just restricted in the stage three patients or that was the overall trial. So just wondering whether you can confirm or adjust his comments that are set on record. And then secondly, just the potential impact of going from a third micrometastatic in the FAPE-1-2 study to two-thirds into PAS-001 and any sort of impact that we could see there. Thanks very much.

So I don't recall exactly what he was referring to in that statement. The trial, we haven't released the baseline demographics of the trial. So, you know, essentially to say that it's stage 2B to fully resected stage 4. And in terms of why we believe we can go to that broad eligibility based on the phase 2 data, it's because when you look at the subsets from an efficacy standpoint, they were all consistent. And secondly, we know that the earlier you go, i.e., stage 3A and then stage 2B and 2C, the immune system should be healthier, the tumor burden should be even lower, and so the ability to induce a T cell response and to have those T cells kill, whether it's micrometastatic or still even before it's micrometastatic, should still be there. I think that's what I would say. I don't remember exactly the point about two-thirds micrometastatic.

No worries. Appreciate the response. Thanks. One moment for our next question. The last question comes from Jessica Fowle, JP Morgan. Your line is open.

Hey, guys. Good morning. Thanks for taking my question. Just wanted to confirm two things on INT. First, if the interim in the Phase III adjuvant melanoma trial passes without stopping for efficacy, how will the street learn about that? I guess, is the study simply continuing a material event that we would hear about right away, or would we just hear about that, you know, maybe later in normal course updates? And then the second one on INT is the translational poster at ASCO had a relatively small number of patients relative to the number who were in the phase two. I'm curious if you know what the data looked like in the broader study population. Thank you.

So we will be issuing a press release on that data, Jess, for the interim. And with regard to the second question, the reason that the data set on the translational was only seven patients is because that in-depth T-cell antigenicity required leukophoresis, which is a little bit more burdensome to the patients than just collecting a tube of blood and so the patients have to consent to that and so we do hope to expand that because we do think that that degree of biomarker analysis is important for understanding the mechanism of the drug and actually we're also looking at ways and we're exploring ways to try and disentangle T-cell immunogenicity without having to do leukoparesis. So that's still exploratory but more to come on that. That's the reason why there were only seven patients.

Thank you.

This concludes our Q&A session. I turn the call back to Stéphane for any remarks.

Thank you very much, everybody, for joining. We look forward to speaking to many of you in the coming days and weeks, and have a great day and weekend. Bye.

Ladies and gentlemen, this concludes today's presentation. We thank you for your participation. You may now disconnect and have a wonderful day.