Our first question comes from Salveen Richter with Goldman Sachs.

Two questions for me. One is in the case that the Phase III Intismeran 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 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 very much. A lot of questions in there. I think with regard to the Phase III -- to your first question, if the Phase III INT study in melanoma continues, 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 Intismeran is positive, what's the read-through? I think it's a very important question and one I've given a lot of thought to. I think there are several important things we need to see here. One is, 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 answer to that -- the data that we've shown at ASCO confirms that we do give -- 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 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 in those other tumors.

And Salveen, 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 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 if there is an opportunity there.

Our next question comes from Tyler Van Buren with TD Cowen.

Another one on the Phase III melanoma INT readout. Forgive me, but I have to ask for more granularity on timing. 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, good to hear from you. So we're not going to disclose any more details around the specific timing aside from that it's second half in terms of powering. I think in terms of confidence, the fact that we had this very strong randomized Phase II data that had consistent efficacy in all the subsets was very promising to me. And the fact, as I mentioned, that the translational data confirms the mechanism of action. I don't think that there's anything else that can be done ahead of a randomized Phase III. And so that's what we're conducting.

Got it. And if it succeeds in the Phase III, 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?

Yes. So priority review will always be subject to the data and -- but we certainly hope, certainly, if we're successful that it will be under consideration and then an accelerated review process is possible. As David said, we are 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 will be supported by any profile that looked like the Phase II. 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.

Our next question comes from Ellie Merle with Barclays.

Just 2 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 was any learnings in terms of how you think about the algorithm for the selection of the neoantigens since there seemed to be variability between patients in terms of the number of neoantigens that patients had immune responses for. So curious how you're thinking about that and potential ways that you could theoretically optimize the selection of the neoantigens.

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 U.S. 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 2 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 there's a potential to address such a situation. And then the second step is 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 1 neoantigen reactive T cell in order for there to be activity. Of course, the more the -- 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.

Our next question comes from Terence Flynn with Morgan Stanley.

Great. 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?

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 III trial that's been published in the New England Journal relative to standard dose that it really is in the enhanced category from our perspective. And importantly, offer 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.

Our next question comes from Cory Kasimov with Evercore ISI.

I wanted to also ask on Intismeran, but on the RCC front. And can you speak to the immunogenicity data that you have that kind of gives you confidence that Intismeran works as well in low TMB RCC as what you've seen so far in melanoma and non-small cell lung cancer?

So that trial is still ongoing. So we don't actually have that data yet. But 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 II melanoma study, which is now through 5 years, we had previously published or presented that TMB did not correlate with the difference. In fact, a 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.

Yes. And I guess just to be clear, I was wondering that kind of where the confidence came from recognizing you don't -- we're waiting on that data later this year or next.

Yes. 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 II and the totality of data we have around that.

Our next question comes from Andrew Tsai with Jefferies.

So just thinking about your clinical Horizon 2 wave of assets coming. First, for the IDO compound, it 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 T cell 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, Andrew. So Horizon 2, I'm glad you picked up on that. 4359, which is the IDO 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 II 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 second -- in terms of your question about what is the bar for approval in second line for single-arm trials, 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 nivo 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 2 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 2 targets. That's the first time ever 2 T-cell engagers have been combined. And so for us, the reason we're excited is we have the first 3 T-cell engagers in a single product ever being studied. And as you mentioned, we're studying 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 3 T-cell engagers, 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.

Our next question comes from Courtney Breen with Bernstein.

Just a couple of others. I want to push a little bit further on norovirus and the update there. Obviously, the question I think many of us are asking is, is this enrollment? Is this an efficacy? Or is this an event 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 6 months? And what might be the changes or the evolution required longer term with -- 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. The -- first on the question of noro, again, limited in what I can say because the trial remains blinded. But suffice to say, we have -- we are going forward with another season this year. We have been able to enroll the trial, which I think was your question, the cohorts, 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 have come a -- 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 as 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 infection. And ultimately, we will go 1 more season we expect this winter for norovirus 1403.

Thank you, Stephen. So in terms of context, as we talked about in the press release when we announced the position of Ester. Basically, if you look at the business, as you know, we have 3 products on the market today. We have since the spring, a fourth product approved in mCOMBRIAX, the flu COVID combo, which we are preparing the launch for 2027. Potentially a fifth product approved in H2, which, of course, flu, as we talked about before. So as you can see, just what is just in front of us, there's a very, very large growing IV pipeline of product. And the other piece, as well 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 set up during the pandemic. But this partnership expires, as we 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 III data potentially in the second half of the year, given the trend. And so as you can imagine, Moderna and our Merck colleagues have been very active. Stephen talked about manufacturing a minute ago, but they have been very active on the commercial side of the house in terms of medical affairs, marketing, commercial. And so that's another piece where Ester 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 said PA because it's a time-driven Phase III. We should have a data this year. Of course, its partners will recall our team, 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 the company coming ahead of us, we feel that this role was important. And also the new role for Stephen, who is really overseeing IV, INT and rare from a kind of a general management to make sure that all the functions are integrated together. So it's just us getting ready for the next stage of growth of the company that's exciting.

Our next question comes from Michael Yee with UBS.

We have 2 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 IIb, 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 expectations for the interim versus the final where you could have a nonproportional hazard ratio where the effect size gets better over time due to the way the drug works. That's question number one is the thought around the effect size getting better over time and a nonproportional hazard ratio. The second question is on the COVID flu combo in Europe. Can you just remind us at what point you engage in conversations to do contracting for that? Because I guess you could have actually revenues for that in '27 and when we get visibility on that?

Michael, I'll take the first question. So we're not going to disclose anything on the statistical analysis plan, but I do think there is maybe 2 key points to highlight. The first is if you remember back to the Phase II study, of course, updated at ASCO, there was, as you said, somewhat of a nonproportional hazard with about 12 months for really strong separation to occur. The good news in the Phase III study, which was designed with Merck, who has a lot of expertise in melanoma is that it 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?

Yes. 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. So 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 STIKO or others have begun to contemplate the combo vaccine. And then as I said, in other countries, we're -- 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 of the timing of their flu or COVID tenders, 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. We have a lot of work to do in Europe to drive that growth. We think that there's real enthusiasm for the product. Obviously, we have it ourselves. And we're working hard to start impacting as early as '27, but really build the business over the couple of years thereafter.

Our next question comes from Geoffrey Meacham with Citigroup.

I just have a couple of quick ones. I guess for Jamey, 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 3927. Just wanted to get a sense for what determines the timing, maybe the regulatory usability of the readout. I wasn't sure what you guys are looking for from an effect size or from a clinical meaningful standpoint.

Yes. Thanks, Geoff, for the question. I'll take the first one on revenue. So we're sitting pretty good after the first half year in terms of $0.5 billion in revenue, roughly 70% international, 30% in the U.S. And your question is getting at where is the upside, where is 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. 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 volume. 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 into 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 year. 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.

With regard to the question on PA, the time -- 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 with our therapy. And so that's why we have confidence or hope for this trial.

Our next question comes from Myles Minter with William Blair.

Congrats on the quarter. My question is just one on clarification. I think Dr. Carlino at ASCO mentioned in INTerpath-001 that approximately 2/3 of patients would have micrometastatic disease. It's a little bit confusing to me as to whether that was just restricted in the Stage III patients, so that was the overall trial. So just wondering whether you can confirm or adjust his comments that are said on record. And then secondly, just the potential impact of going from 1/3 micrometastatic in the Phase I/II study to 2/3 in INTerpath-001 and any sort of impact that we could see there?

So I don't recall exactly what he was referring to in that statement. But the trial -- we haven't released the baseline demographics of the trial. So essentially to say that it's Stage IIB to fully resected Stage IV. And in terms of why we believe we can go to that broad eligibility based on the Phase II data, it's because when you look at the subsets of -- from an efficacy standpoint, they were all consistent. And secondly, we know that the earlier you go, i.e., Stage IIIA and then Stage IIB and IIC 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. So I think that's what I would say. I'm not -- I don't remember exactly the point about 2/3 micrometastatic.

The last question comes from Jessica Fye with JPMorgan.

Just wanted to confirm 2 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 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 II. I'm curious if you know what the data looked like in the broader study population.

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 7 patients is because that in-depth T-cell antigenicity required leukapheresis, 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 leukapheresis. So that's still exploratory, but more to come on that. That's the reason why there were only 7 patients.

This concludes our Q&A session. I'd like to 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 does conclude today's presentation. We thank you for your participation. You may now disconnect, and have a wonderful day.