Quarter 1
Q1 2026 Earnings Call — May 1, 2026
Salveen Richter (Goldman Sachs): So you newly disclosed initiation of a phase three study for antismoron as monotherapy and in combination with K2 to sub-Q for the treatment of high-risk stage one non-small cell lung. Can you just, and you spoke to it a little bit, but could you discuss your strategy to pursue this line and where it fits into the treatment landscape, and why pursue a monotherapy here in addition to the combination? Thank you.
Executive Name (Title): Thank you for the question, Salveen. We and our partner, Merck, have been really excited by the clinical data that we've seen within TIS4N to date, including the phase two. And it's important to highlight the two pieces of that. One is obviously the efficacy signal we see, but the second is the remarkable safety profile associated with that efficacy. There is really no significant increase in serious or grade three events when you get combination IO-IO-like benefit. So the real question for us has been, could we get that benefit risk profile in a monotherapy context? Could Intis Moran provide IO-like protection against a relapse or recurrence of disease with a profile that really looks like a, you know, vaccine? The best opportunity for us to do that, we and Merck have decided, is across a couple of studies. Now, the first I previously discussed was in bladder cancer, but we ultimately decided that in lung cancer, given the incredibly high burden of disease, the right approach there was to go into a phase three, potentially pivotal study.
In that context, as Stefan mentioned, as you referenced, standard of care more often than not is surgery and then watchful waiting. And so essentially there is no other intervention. And we're looking at, therefore, INT as monotherapy as opposed to just surgery and watchful waiting for high-risk stage 1 disease. Now, we're also going to look at whether or not there's an incremental benefit of combining INT with Keytruda in that setting. Our goal, simply put, is to intervene early, prevent the relapse or recurrence from ever happening, and in so doing, try and achieve cures in the earliest stages of diseases. The benefit-risk there needs to have a very good safety profile, and we really do think that the monotherapy safety profile of INT will be really strongly supportive if we can see in that Phase III study a strong efficacy signal. So, we and Merck have been talking about this one for a while. Our strategy has been to focus on the adjuvant settings, but we have started, as you know, some metastatic studies. But we have always wanted to move earlier, signal that from the beginning, because of that benefit-risk profile of INT.
And we're really excited to see the potential now in stage one disease in a phase three lung cancer trial. Thank you.
Jessica (JP Morgan): With a significant amount of international sales this quarter, I remember I think the UK order from last year got pushed into early 26. I'm just trying to think about those contracts and the right way to think about what more could come from the UK for the remainder of 26. Is it possible this is a double order year? And maybe you could just elaborate on how that works. Thank you.
Executive Name (Title): Yeah, sure. I'll take that. The delivery that happened in the first quarter is for their spring campaign. And so for in the United Kingdom, there is a recommendation for both spring and fall booster for the targeted population, those over the age of 75 or with significant risk factors. And so a second campaign is planned for the fall. And so the third and fourth quarter of this year. And that would be an additional delivery later this year. Thank you.
Terrence Flynn (Morgan Stanley): Just wondering if you can be any more specific about the timing of the interim phase three of the INT and adjuvant melanoma. I know you said 2026, but can you refine that at all at this point? And then, maybe talk to the range of potential outcomes there. Are there only two outcomes, either the trial hits at the interim and continues as planned, or is futility also a potential outcome on this interim? Thank you.
Executive Name (Title): Thank you for both questions. So I will disappoint in the sense that we won't refine that guidance. We have said we are confident, based on the vendor crew, that we will see an interim analysis conducted in 2026. You know, I shouldn't say more except that that confidence should indicate where we think we are. On the question of the outcomes, there is not a built-in futility assessment. The interim analysis is either to declare early success or to continue to accrue events in the trial towards a subsequent interim analysis or a final analysis, both of which could happen in the years ahead. The study is very well-powered and has been balanced in terms of its accrual, and so we have continued to accrue events in a way that we would expect. And therefore, we're optimistic about that interim analysis. But obviously, if we have not yet hit the critical hazard ratio to declare early success, we will have the benefit of continuing to look at more events afterwards. But futility is not a part of the current plan. Thank you.
Luca (RBC): Maybe Jamie on IP, can you just walk us through why the legal team deemed the additional $1.3 billion charge on 1498 as not probable? I guess the question is, what gives you confidence that you will ultimately prevail there? And then maybe just kind of bigger picture, remind us the timeline of when the final ruling could come. And then maybe quickly, Stephen, what's the latest thinking on flu in the U.S. ahead of the PDUFA? You know, we obviously now have a new acting director of CBER at last night in Catherine's drama. So I wonder if you have had any interactions with her and whether you think that having her in the seat is incrementally positive or incrementally negative for you. So any call there, much appreciated. Thanks so much.
Executive Name (Title): Yeah, thanks for the question, Luca. I think I may disappoint as well because we're not really going to comment too much on the merits of the trial. So all I can say is our legal team, ourselves, we are confident and therefore we believe it's improbable that we would lose and therefore have not recorded anything. From a timeline perspective, always difficult to exactly read, but we think that it could be perhaps late 2027, maybe into 2028 is where we think that this might be resolved. But again, that's a moving target. Thank you. And for the question on the FDA and particularly the Flu 1010 program, we continue to progress well in that review in the normal back and forth with the review team and the folks in the Office of Vaccines towards our PDUFA date, obviously at this point through a mid-cycle. And we would describe that as a pretty normal course, the kinds of exchanges we're having. And so we're encouraged by that and look forward to that August 5th PDUFA date. Obviously, we'll work hard to answer any questions, any remaining questions that the FDA has as they complete that review.
As to the senior leadership, whether it's CBER or otherwise, we don't usually interact with them in these reviews at all. Really, this is the review staff, the folks in the Office of Vaccines, and that is the only place that we've been going back and forth, and we don't expect any impact. Certainly didn't, you know, before today or after as a result of the new acting director. We do look forward to working with the leadership of CBER broadly across our portfolio. So the, you know, 1010 flu vaccine review continues somewhat independently. But we have a large portfolio of other products from intismoran INT to norovirus to our first rare disease program, the propionic acidemia program, all of which we hope have pivotal readouts this year, and we look forward to bringing those forward. So it's an exciting time for us, hopefully for the field, and we are very grateful for the partnership across FDA and CBER as we try to bring these medicines forward to patients. Thanks so much.
Tyler Van Vuren (TD Securities): For the phase three antithrombin management melanoma top line data, can you remind us what it is powered for? And perhaps more importantly, can you give us your latest thoughts on what constitutes success from a clinical standpoint and what you need to show in RFS on an absolute basis or as we think about relative benefit there? Thank you.
Executive Name (Title): Thank you, Tyler, for the question. So we haven't disclosed the powering assumptions for the IAEA. Suffice it to say, the phase two data had a really strong hazard ratio, very narrowly missed, and a substantially smaller powering 150, 160 participants as opposed to 1,100. And so we think we are well-powered, very well-powered if we see a similar hazard ratio. That would obviously be a huge success. But to your second part of your question on sort of the range of things that we would be pleased with, obviously anything that looked like the phase two would be spectacular. But candidly, we think the opportunity for benefit could be anywhere between that 0.5 that we saw in a number like 0.8, where there's a significant benefit still in terms of survival and treatment of that, of melanoma, adjuvant melanoma, stage three melanoma. Now, across that range, is, you know, a wide range of outcomes that we'd want to understand the raw data, you know, what's happening. If you see really strong RFS and really strong, eventually, overall survival, as we've seen so far in the Phase II study, that's encouraging.
You know, if you saw maybe that the overall survival or distant metastasis data was better, even if the RFS was not, that would probably equally be encouraging. And so there's a range of outcomes for how we would declare success that will depend upon the different clinical benefits that we see in the study. But for now, we feel like we are well-powered going into that interim analysis. If not, we look forward to the subsequent interim analyses. And we think there are a range of outcomes here, ranging from the phase two results to a whole bunch of events that are much more modest that could still be really meaningful patients and move forward successfully commercially as a treatment for stage three melanoma. Thank you.
Ellie Merle (Barclays): Curious what your expectations are for timing for data from RCC and muscle invasive bladder cancer. And can you elaborate on what good data would look like in these indications and then what the next steps would be in those indications if the data are positive? Thanks so much.
Executive Name (Title): Yeah, thank you for the question. As we've previously said, both of those randomized phase two studies are fully enrolled, about 300 participants in each. And so we're really excited to fill in the picture on the strength of performance for INT across a range of different tumors. I would point particularly to the RCC as one that we're interested to see whether or not we can provide a really meaningful clinical benefit, because we still think there is an opportunity, headroom for improvement there that's quite significant. Now, those are event-driven trials, and we did want to protect the registrational possibility for those trials. So we're blinded, and we're accruing events towards that first interim analysis in both. For obvious reasons, if possible, we would want those studies to be registrational. And so we want to make sure we accrue a good number of events and that we treat those analyses the right way. And because that's hard to guide right now, we don't exactly know when potentially this year or even early next year that those results could come in because they are event-driven analyses.
But when we have accrued sufficient cases to conduct that bind analysis, we will definitely be doing so. And all of us are eager to see the results because it will help not only guide whether or not those products or those indications are reasonable to move forward more quickly, again, potentially to a registrational study or towards a phase three pivotal study, which we would look to start quickly. But also they fill in that picture of how broadly INT is going to play. And in some ways, if you think of RCC as an example of a place where it's relatively far from melanoma in terms of mutational burden, and therefore an opportunity for us to demonstrate a potential benefit that would then widen the aperture of where we think INT might have a role. So we're keen to see that data, but we are blinded at this point. We are following those events, and we are eager to provide updates once we have more. But for now, we can't guide on when that timing would be. Thank you.
Michael Yee (UBS): We had two questions on INT. The first was on the melanoma study. Would we expect that that's a similarly designed protocol as it relates to the interim? I recall that the phase two strongly hit at the interim, and so just trying to understand if a similar type of standard interim was built in here, such that if it doesn't stop at the interim, it would imply some sort of different hazard ratio for the first interim versus the second interim. Similarly, on the renal study, we understand that it's a much slower progressing tumor. If you look at the Keytruda adjuvant studies, just trying to understand how it would be possible that a potential interim would come this year, or that's a much differently designed study in terms of an interim? Thank you.
Executive Name (Title): Yeah, thank you, Michael, for both questions. So, first, we obviously haven't given any statistical guidance on the phase three interim analysis, but suffice it to say, as I just did a moment ago, we wouldn't be conducting the interim unless we thought there was a chance of success. And in that sense, you know, we are not defining that as the hazard ratio that existed in the phase two. There were some differences in the population, but certainly that would be a situation we would want to have a relatively early look at. And so it's somewhere between there and obviously not significant that we're looking for. We are really excited, but we also just need to wait until the data mature and see those results. And so we're optimistic about that first interim. But it's fair to say that if it isn't successful, there's still opportunity in the second and the final. And we definitely have reserved alpha for both of those for what we think would still be commercially important products. So that's point one. Now, on the renal, the renal is RCC is, as you said, the events can happen more slowly.
There is a benefit, obviously, from Keytruda, but there's substantial headroom still. Even if you look to the combination products, Keytruda plus Belzu, Merck has just had a great success there, with a hazard ratio of 0.72. There's still headroom, even above that, for improvement in terms of relapse-free survival. And so we're keen to look at that result. There are about 300 participants enrolled in that study. And I'll remind you as a reference, that's about twice as large as the phase 2B adjuvant melanoma study that we've all been speaking so much about. We're not intending to power that as a registrational study, but it has registrational potential. And what that means is we could have a lower statistical threshold for declaring that there's a strong result there, a strong signal. Think again like what we saw in the phase 2B with melanoma. The key there, though, would be we would not want to unblind that study if you had a lower threshold, call it 0.1, alpha of 0.1, we wouldn't want to unblind the study if it was trending towards statistical significance and registration potential.
And so that's the key unknown in that RCC study in terms of timing, is we will hit a trigger for conducting a minute analysis based on events. The DSMB will look at that result and then advise us whether it's appropriate to declare early success or whether to remain blinded or, you know, alternative outcomes, you know, that are more like futility, but that would cause us to want to look at that data and quickly determine whether or not we want to run a phase three. And so it's a high degree of uncertainty of what that looks like, but it's all about trying to make sure that if we have a drug here, a strong signal in RCC with registrational potential, we did not disrupt that. or if it's strong and needs a phase three more powered analysis, that we get that going quickly. And I think that's the decision that lies ahead of us in partnership with the DSMB. Got it. Thank you, guys.
Courtney Breen (Bernstein): Just a couple more on INT. What I wanted to understand as we're getting closer and closer to kind of this becoming a meaningful part of models in future years, there's obviously still some big decisions to make on price, but also on revenue recognition between you and your partner. Number one, can you help us kind of understand the parameters here and kind of help us think through what this might look like in terms of Moderna's kind of realized contribution in the PML, recognizing that it is. And then second, in the stage one monotherapy and combination study, can you just again help us understand a little bit about that stage one prevalence of diagnosis relative to later stages lung cancer is obviously relatively compared to other cancers diagnosed quite late. So it would be helpful to understand how you think about this market and potential building if we can see kind of some new opportunities for those patients. And speaking of that opportunity, any comments on kind of what the bar looks like, particularly compared to watching and waiting to know? Thank you.
Executive Name (Title): Yeah, thanks, Courtney. I think we're breaking up a little bit, but I think the first question was around RevRec as it pertains to INTs. Let me take that one. And I'll put a caveat out there that we don't even have the product approved. We're working with our auditors. It's not a traditional joint venture. So but this is I'll give you to the best of our knowledge how we think it'll work. So it'll end up being that we deliver the product to Merck because they're obviously the market authorization holder and they were solid on to the customer. So that will be the first part of our transaction. And so you can imagine some amount of our cogs plus some markup. Thereafter, whatever the profit split is, then we will take that share, our share of that or 50%. So it ends up being naturally somewhat greater than 50% of the profit share because it's predicated upon first shipping the product and having some markup on that and then taking the margin on top of that. So that will change over time because as we've laid out before, we're working on our cost of goods sold and with that will continue to come down over time as we continue to drive automation.
So it'll start a little higher as our cost of goods sold will obviously like any product starts higher and then gets more productive over time. But that's the general framework. And I hope that helps. But again, we hope to be in that position next year to be able to start recognizing that revenue. Great. Cancer stage one. So lung cancer really represents a pretty unique opportunity because screening through x-rays has actually been an important intervention for identifying early stage disease, stage one disease. Now, the majority of diagnoses still show up later, you know, stage three, stage four in particular, but you're seeing an increase almost a third, north of 30% of diagnoses are now earlier stage, stage one, stage two. And that has grown over the last decade and hopefully continues to grow through better screening, including a relatively easy intervention, you know, a chest x-ray that your primary care doctor can provide. So we do hope and expect that there's a big push on earlier, catching lung cancer earlier, and that that is a natural place, therefore, to try and intercept and intervene if you have a great benefit-risk profile.
Again, to be proven, but we know we have the safety profile. And if we can do that, then we'll be able to dramatically impact the number of stage four or stage three and four diagnoses that start to show up. You've already seen evidence of that, right? I mean, if you look in the United States over the last decade or two, there has been an increase in the number of diagnoses that are the percentage of diagnoses that are happening in earlier stage and a commensurate decrease that are happening in the later stages. And so we do think it's a unique tumor opportunity for us to go demonstrate stage one intervention because of that screening regime around chest x-rays and the overall trajectory in the field. Thank you.
Jeff Meacham (Citigroup): I have two quick ones. The first one on Entise Moran, as you grow the experience and data here, I know most of the trials are in combo with Keytruda, but are there other IO combo mechanisms that could also bear fruit? or is that better addressed with the rest of your oncology pipeline? And the second one on norovirus, as we get closer to data, do you have any updated view of what success looks like here, just given the serative care? My sense is a significant benefit is all you need, but I wanted to get your guys' perspective. Thank you.
Executive Name (Title): Yeah, thanks for both questions. So, first, on the alternative IO-IO combinations, you know, we are looking in the adjuvant setting and earlier in many of these phase three studies. We do have a metastatic melanoma study, as you know. But we, in that context, generally IO-IO combinations and the toxicity associated with them has not been seen as advantageous. And so, for now, most of our focus is on the combination with the PD-1 and Keytruda because of our partner Merck. We would be interested in subsequent studies in exploring alternative IO combinations. But as you kind of alluded to, that's already something we're starting to do in the rest of our pipeline. And in particular, I'd point to 4359, where we are looking in metastatic melanoma and alternative regimens, CTLA-4 plus PD-1 combinations, IPI and NEVO as an example, have been important interventions showing benefits in those populations. And that's a place where if we want to add a third IO agent for hopefully some benefit, we are doing some early phase one, two exploratory work right now.
So you might see just as a function of the huge amount of work we're already doing in INT, you might see us first explore those other combinations for our cancer vaccines platform in the other off the shelf context first. But that doesn't rule out that in the future we might not explore the use of INT on top of other regimens. Certainly both ourselves and our partner Merck are interested in that. Now on the norovirus side, I think you hit the nail on the head. We think given that there is not currently an approved vaccine for norovirus, and given that particularly for those at highest risk, those over the age of 75, those that have other medical comorbidities, there really is a high societal and medical cost associated with a profound dehydration that can happen with even just what might feel like a two-day norovirus infection. Not just hospitalization, but significant exacerbations of underlying medical diseases as well, and some death. And so that population, anything that can be done to reduce that burden would be ultimately value creating for the healthcare system, put aside the benefits for the individual patient. And so, we think statistical significance is the bar.
You know, obviously, we want to see a vaccine efficacy that's also meaningful and so north of 50%. But given that there currently is no standard of care or treatment, we would take anything above there as a success. Great. Thank you.
Corey Casmo (Evercore ISI): So wondering how critical is it to demonstrate an overall survival benefit in intrapath of O1s given the challenges of showing OS and adjuvant melanoma? Do you believe physicians would interpret the data set any differently absent a clear OS signal? Thank you.
Executive Name (Title): So, I'd make a couple of observations. So, first, RFS is a pretty good predictor. I mean, this is a relapse-free survival. Again, it's not progression-free survival. It is survival and tends to correlate. And if you look at our Phase II study, you know, we have released previously the RFS, DMFS, and even OS trend data. We look forward to the ASCO presentation to provide the five-year update and the view on RFS, DMFS, and OS. And, you know, I would point to that presentation and the data, and, and we hope that that will provide confidence for physicians, for healthcare systems, for patients, on that relationship in this case, and in the case of intesmerin and combination of the adjuvant melanoma setting, and that that would provide sufficient confidence to move forward if the Phase 3 is positive. Now, the Phase 3 data, we will follow OS, and we're through five years in the Phase 2, so it will take us some time to get to that same level of data in the Phase 3, but it will be a part of the trials going forward and can provide a significant degree of confidence going forward. But again, RFS really is survival in this case. That's helpful. Thank you.
Simon Baker (Rothschild and Co. Redburn): Just looking at the Q2 revenues, a couple of quick questions. Firstly, could you give us any color on the split, or should we assume that the entirety is spike VACs? And also, Jamie, I wonder if you could give us any comments on phasing. It was a very strong number against our expectations. But I just wanted to know if there was any pull through of expected revenues from Q2, particularly with some of those governmental orders outside the US. Thanks so much.
Executive Name (Title): Yeah, thanks, Simon. So let me address the first question as it pertains to product split. This was largely the majority is COVID still. So we have not been, as we've always said, we don't anticipate RSV being a significant growth driver in the year 2026. We believe that will take a little bit of time for us. So this is still primarily COVID related. As for the timing, we laid out the second quarter. So I think maybe
your question is more on the second half. But for the second quarter, we laid out $50 to $100 million in the second quarter. So that should bring our first half to almost a half a billion dollars of revenue. And that, if you look at that, is probably $400 million outside the United States and $100 million in the United States. So let me talk to the timing of the year and give big picture and kind of compare it to last year. Last year we had $700 million of sales outside the United States and it was a hundred in the first half and 600 in the second half. So with 400 this half in the first half this year, if we repeat last year, that's a billion dollars. And we've been talking about saying that our mix between the U.S. and international is going to be about a 50 50 split. So if we just repeat last year, that should get us a billion dollars. And then the US last year was $1.2 billion. I said in my prepared remarks that we're expecting some amount of decline and we've modeled for that. So hopefully that gives you a little bit of the phasing and timing here.
And the last point I'll say is back to a question that was asked earlier is in the second half of last year, we didn't have any UK revenue. So to Stephen's earlier point that if there is a fall season in last year, $600 million outside the United States, we did not have any UK. There are other puts and takes. That's why we've guided up to 10%. I'm not giving explicit guidance here, but I'm trying to give you the picture and contextualize what the year might look like from a US versus OUS split.
Andrew Sy (Jefferies): It's a bigger picture question. I'm just curious what your guys' latest thoughts are on BD and even considering technology or assets beyond mRNA? Does it make sense to add more assets to your pipeline, or do you think you're right-sized for now? Thank you.
Quarter 2
Q4 2025 Earnings Call — February 13, 2026
Terrence Flynn (Morgan Stanley): Hi. Thanks so much for taking the question. I had two part. I guess the first one is just on the flu RTF, implications for the 2028 cash flow break-even guidance, and then timing of the type A meeting, like when you might get some visibility on next steps. And then the INT program in adjuvant melanoma, I know that's a very important program and catalyst for the company. And so can you refine at all the timing of that data, whether it's going to be first half or second half? Thank you so much.
Management: Sure. Maybe I'll take the questions on regulatory first, and then Jamie hand it over to you on any breakeven implications. So we're actually very pleased that the flu file is under review now in Europe, Canada, Australia. We'll be filing in additional countries this year. And all of that is with an eye towards having that start to contribute, as I said a moment ago, in 2027, in the fall of 2027, to our growth. We also are pleased that the flu COVID combination product remains under review and making progress in Europe for this year. As relates to the U.S. timing, it really, we need to engage with the FDA in the type A meeting. That's usually 30 days as a process and understand from them what is going to be required to get that product moving forward in the U.S. We absolutely feel that American seniors should have access to the same innovations. We do think this year, in particular, where there's a potential for a mismatch in one of the strains, it's particularly important that technologies like Moderna's mRNA platform are used to advance new and potentially improved products. But at this point, until we have that type A meeting, we won't really know how quickly we can get moving forward with a 1010 file in the U.S. as we've been doing outside the U.S. Jamie?
Jamie (Title): Yeah. So, Terrence, thanks for the question. I appreciate it, and I recognize that it's on investors' minds. As Stephen just said, though, this is a bit of a fresh and fluid situation. And without understanding the resolution of what is next for our fluid product, it's a little bit difficult to comment
at this time.
But here's what I would say. If you go back to the growth drivers we laid out at Analyst Day, as well as Stephen had in his prepared remarks, we have 10 large shots on goal to increase revenue over the coming years, all with a wide range of potential outcomes. And Stephen mentioned some of the progress. We announced our long-term partnerships with Mexico and Taiwan. We're excited about, as I said, we're excited to deliver for the UK and Australia this year, which will be substantial revenue growth. NextBike had a great first year. We're excited about the second year, both in the U.S. and outside the United States. We're looking forward to Europe opening up. So it's really, there's still so many scenarios that could happen here, Terrence, that it's a little bit too early to tell. On top of that, we have a ton of momentum on productivity and what we're doing from a cost perspective. So we're really excited about our financial profile. We ended the year with over $8 billion in cash. We have a ton of momentum from a cost perspective, and we have a lot of opportunities for growth. So at this point, without knowing resolution to what's going to happen on flu, I think it's a little too early to comment.
Management: And on INT, the second question, we don't have, obviously, more specific guidance than we previously put out there. I'd highlight, as I said a moment ago, that there are five histologies now under review or under different stages of clinical development. So INT for melanoma, the adjuvant melanoma study, is one that we are confident we'll read out this year. It is an event-driven trial, and so it will depend upon the accrual of those events. We have RCC, so renal cell and bladder, now fully enrolled. And again, those are going to be event-driven and milestone-driven readouts, and so it's possible. And then the phase one data that we referenced before for our periadjuvant gastric and adjuvant pancreatic monotherapy cohorts. And so it's going to be a busy year for us over the next number of months, but we don't have more specific guidance because some of the most important readouts are ultimately event-driven. Thank you.
Elizabeth (Goldman Sachs): We wanted to ask about the flu and COVID combination vaccine and just given the RTF-41010, how should we think about this refiling and is there any read-through from a regulatory standpoint in the U.S.? And then maybe just remind us of the study data that went into the submission initially and what the latest thinking is on what might needed to be added for refiling. And then a second question on, in Tismoran, wanted your thoughts on which of those five histologies you just mentioned have the highest probability of success kind of based on the read-through from data generated to date. Thank you so much.
Management: Thanks for both questions. So first, on the 1083 file, again, I'll underscore that we're hoping for approval of the flu-COVID combination product in Europe first, in this year, and so we'll move forward there. As relates to the U.S., we were holding back on refiling the combo vaccine until we'd completed some portion of the review of the flu vaccine. With the refusal to start the review of the flu vaccine, I think that is now gated on, again, the feedback from the Type A meeting, which we haven't had, about what more would be necessary for us to refile for the mRNA 1010 program. And then we would be able to provide more clarity on the flu COVID program and refiling there. Again, all of this in the U.S. because all of those files are moving forward internationally. You asked about the data that was in the file. We had a phase three study for the mRNA 1010 file, which we have previously presented the results on. And actually, it's out for a peer review publication right now. But really excited by that phase three study, which was a randomized 41,000 person study that we had agreed with the FDA and agencies around the world with prior to initiation. In that study,
as a reminder, we saw 27% superior relative vaccine efficacy compared to the standard dose control.
And just to give you a sense of where that stands relative to comparators, you know, the two of the licensed preferentially recommended vaccines for those over the age of 65 had run essentially the same study design, one of them even with exactly the same comparator. And those, if you look at the USPI for flu zone, they had seen 24% relative vaccine efficacy for flu block. If you look in there, you see USPI will see 30% relative vaccine efficacy. So at 27%, we felt very good that we were in line in demonstrating superiority in exactly the same way that those standard of cares have in the same population as those over the age of 65. We also ran a phase three study, an immunogenicity and safety study, comparing our vaccine candidate for flu against flu zone high dose. And in that case, we showed statistical superiority to flu zone high dose on immunogenicity. That study has been published in the journal Vaccine and is available, I think, on our website for those who are interested. So, that package was in the initial file. We think it's a very comprehensive data set.
We do think if we can get the review initiated, it will support the use of the product, but we do need to understand first from FDA in that Type A meeting what they would need to initiate the review of the file that they previously had agreed to review. Moving to antismorin, I think it's obvious that you asked where we see the highest probability of success. It's hard to argue with the Phase IIb results that we have for adjuvant melanoma. As we announced last month, the five-year survival data continues to look really strong, approximately a 50 percent reduction in the rates of relapse or death from melanoma. Real stability in those curves through now five years. And if you ask me where do I, you know, think the read-through of that is, I think it's clearly, we hope, into the phase three adjuvant melanoma study that is testing in largely the same population and exactly the same standard of care. You know, I think if it works, if we see that there, one of the reasons we and our partner Merck went in with renal cell and bladder was we thought muscle invasive urothelial cell carcinoma is we thought those would be places where we might also see relatively quick read through.
And so I hope that the, you know, that those also have positive readouts. But I think if you're asking where we think the probability of success is highest, it's clearly in the, it's in the phase three adjuvant melanoma.
Eliana Merle (Barclays): Hey, guys. Thanks for taking the question. Just can you elaborate a little bit on how you're thinking about the European COVID vaccination market and how you see the vaccination rate and pricing evolving there and also how outside of the U.S. you're thinking about the pathway for a potential flu-COVID combination vaccine approval? And then also on that topic around flu, just in your filings for flu in Europe and Canada, has there been any discussion around potential strain selection in the future and potentially selecting the strains closer to the season start? Thanks.
Management: Yeah, thank you for all three. So first I'll take the combination question, or actually the COVID question. So MNEXT Spike is moving forward with approvals internationally, and we're really pleased with the profile of that product. As I'll remind you, we had demonstrated in that phase three study, higher relative vaccine efficacy. In fact, in a post hoc analysis, very high, approximately 25% higher relative vaccine efficacy compared to NexBike in older adults with comorbidities. And so really do think it's got a strong profile as the European COVID market reopens. Now, as to pricing, you know, we haven't issued that yet, but we do believe that the current market is, as we've shared, approximately $700 million today. And that doesn't account for wastage that exists in the market. There are many doses that are being, more doses that are being purchased under that pandemic contract that are not getting used. That estimate of approximately $700 million is just what we see as shots in arms. So we do believe that market will be larger than that, larger than even if we see nothing more than the approximately 20 million shots in arms that currently are happening.
And we do hope to get a sizable share. We think MNEXT Bike will be a very competitive product profile in that market. And we're scaling up for that launch. As you know, Europe is not one market. It is a series of different markets and some places will compete traditionally with sales and market activities. Other markets are more tender driven and we're preparing for all of that activities really starting this year, but as we said, as a meaningful driver of growth in 27 and beyond. On the combination product, we actually think that's the next step in that strategy. We're very pleased by the Combo product's progress in its international reviews. As we've said, based on timing, we do expect a European review to move forward, and we are hoping for approval this year, which gives us a chance to launch, you know, as early as this year, more likely in 27. Again, it just depends on timing of these events because proximity to the season will make a launch very difficult. But it is clearly a great opportunity for us to move beyond just COVID into a combination product and an opportunity to both expand our share in the COVID space, but also grab share in the flu space.
And we are proceeding with the filings elsewhere. I think we referenced in the PR Canada for that combination product as well and hope to similarly bring forward that innovation because we believe there's strong demand from health systems as well as patients for one shot or one vaccine that does multiple things. Now, as relates to the flu, we have been having those conversations. So, mRNA 1010, as we've proceeded outside of the U.S., there has been strong appetite for the question of better strain matching. And in fact, in some public comments, you've seen some European regulators, but also some from other markets, vocally advocate for later strain selection and more diverse strain selections happening in flu vaccines because of the precedent we've shown with COVID vaccines. I'll remind you that we sometimes forget in the U.S., but in this country, we've actually, the FDA has chosen different strains of COVID vaccine than the rest of the world in two out of the four past seasons. And the data has shown that that better matching for the market has led to slightly better efficacy.
In fact, we ran a clinical trial once head to head back in the bivalent days and showed higher point estimates for efficacy. Which makes sense. A better matched vaccine, you would expect to be better at protecting people. And what we're hearing from the international flu community, including, as I said, in Europe, is quite strong support for that. It's a real question today. I mean, just to make the point, there are a couple of different strains of influenza B circulating around the world right now. In the United States, it is a different strain than is circulating in the rest of the Northern Hemisphere. And there doesn't look like there would be great cross protection. And so it just highlights that the right answer for this fall could be very different from a composition perspective for Europe or North America or other regions. And that's where the technology that we have that has allowed us to tailor and meet regional needs with COVID we think can have an impact. There are many other things we need to do to improve flu vaccines, but this is one we know we can do right now.
Greg (TD Cowen): So some investors have been surprised by the higher than expected cash balance at year end. So can you explain why that occurred and what the additional levers to lower cash costs are moving forward? Thanks.
Management: Yeah, sure, Greg. Maybe I'll just go back to our original guidance. So when we laid out our original guidance, we said one point five to two point five billion dollars of revenue. So two billion dollars at the midpoint. And we said five and a half billion dollars of cash costs. So if you take those two together, it's a three and a half billion dollar usage from a starting point of nine and a half billion dollars, which is why we guided six billion dollars. Since then, revenue essentially came in online. We had 1.944. Let's call that pretty close. And cash cost came in at 4.3. So we beat by $1.2 billion. On top of that, we took $600 million of the initial draw from the loan. So that's now $1.8 billion better. Our capital expenditures were $100 million less than we forecasted at the outset of the year. So that's $1.9 billion better. And then if you look at the working capital, I am really pleased. It doesn't get a lot of attention with how the team has performed. Our receivables are at $180 million. Inventory was flat year over year at $270 million. Payable is at $300 million. We have a net working capital balance of $150 million to which we run this company on.
And that is really incredible performance from the team. And that drove the last $200 million. So I don't think it should be too much of a surprise that it's mostly cash costs for $1.2 billion above our original guidance, the loan. A little bit less capital expenditures and then terrific performance on working capital from the team.
Michael Yee (UBS): First, on the adjuvant Phase III melanoma study, can you remind us that that study has interims built in and then of course a final and so like other design studies you've done there's a certain number of cases accrue you take a look at it and then if it doesn't stop you move to the next case uh next interim can you just describe a little bit how that works um uh and remind us the phase two i think did stop at an interim if that if i was correct there and then on norovirus i don't think anyone's asked on that but uh can you just remind us there you um are enrolling or expect to complete enrollment, and then there's actually a readout, I think, planned this year. What is your confidence level there? I know there's been a lot of disappointments previously, but I think you are targeting a different approach and using three different strains, which I think, I assume you believe will capture the majority of coverage. Can you just remind us there and how you think about that result? Thank you.
Management: Yeah, thanks, Mike, for both questions. So first on the INT Phase III for adjuvant melanoma, you're correct. The first analysis that we'll see this year will be an interim analysis looking at the primary endpoints of relapse-free survival. We have a number of additional analyses. If you get there and we don't have the statistical power to declare early success then, then we would move forward to subsequent analyses and ultimately additional endpoints, including things like distant metastasis-free survival. What I'd remind you is the phase two hit, essentially, its statistical hypothesis at the interim. And then what we've been following since are the others. And we believe we've conservatively designed this study so that if those results are repeated, we would be well-powered to see that in this first interim. But if for whatever reason we're told to continue forward, there would be a subsequent analysis. And that, again, would be event-driven, but presumably would come the year after. As to the norovirus study, we are very excited to see those results potentially this year. Again, a case-driven trial.
As you highlighted, there had been some previous efforts in norovirus. Ours are quite different. So first, the composition of our vaccine, as you highlighted, is a trivalent here, and we are looking at strain-matched efficacy, which is important because it does allow us to make sure that we're looking at the performance of the vaccine, which is matched at strains that are in approximately, in most years, two-thirds to 70% of the circulating norovirus disease. And so that trivalent composition and the VLPs that our technology make, we think, is a differentiator. But perhaps the more important one relative to the trial I think you were referencing is we're looking in seropositive populations, not children. And so earlier studies that have struggled in norovirus have looked at in children, in primary vaccination, you know, often a couple of doses, as opposed to really where the burden of disease is as you become an adult is in older adults, those particularly over the age of 65, where, you know, the threat of really profound dehydration can lead to hospitalization and complications of a whole number of medical comorbidities. And so there's actually even bigger need in that population.
And in that case, it's more of a booster trial. It's much more like, you know, it's a bit like primary vaccination for, you know, whatever it is, RSV or flu or COVID, being very, very different than boosting seropositive people so that they can protect, which is a lot more like what you see with our senior flu, COVID, and RSV vaccines, which have obviously been successful. Norovirus is a different one, but we do believe that that difference in population will make a difference in terms of the ability of a vaccine to help protect them against this disease.
Management: And as a follow-up, do you think that the guidance with FDA or the discussion or regulatory path for this would be very different or, to put it another way, much more obvious than perhaps what's going on in the flu?
Management: So look, Michael, I'd remind that we got three products approved last year in the U.S. or some label expansions, RSV, a new COVID product, and a pediatric COVID. And in those cases, the guidance was different. What we're experiencing with flu is, I think, we hope flu-specific. Our norovirus study, to your point, is a very large placebo-controlled study. And so the refusal to file letter that we have received from the FDA on flu really speaks to a change in their perspective on the comparator used. But in the case of norovirus, there is no comparator to use. And so the comparator in that clinical trial is placebo. If we're able to demonstrate efficacy over placebo, it's hard to argue that there's a problem with the comparator.
Shelby (RBC Capital Markets): Maybe on INT, congrats on the recent five-year data for melanoma, and it's great to see the hazard ratio for RSS is remaining consistent with prior cuts. However, what about OS? I remember at ASCO in 2024, you showed some pretty compelling data with the initial separation of the curves, but the press release this time was silent on OS. How should we read that? Does that mean the OS curves are no longer separated, or are you just keeping the details for maybe an upcoming medical meeting? Any color there. Much appreciated.
Management: Yeah. Let me say it this way. We look forward to sharing the OS curves at an upcoming medical meeting. Where you see relapse-free survival holding, obviously included in relapse-free survival is survival. And so we obviously didn't put that out because we want to make sure that we're able to bring that forward to the community in a place where they can see all of that data. But all data from this five-year interim analysis will be presented at an upcoming medical meeting. Until then, I really shouldn't say more.
Courtney Breen (Bernstein): Just a couple and building off the conversation around the RTF that you got for the flu 1010. We've managed to find kind of an immunogenicity sub-study, I think, of that phase three efficacy study, which suggested, and it was a very small population of that study, suggested there was a 50-50 ratio between those under and over 65% can you just remind us or share with us what percentage of patients in that efficacy study were 65 or older? And then additionally, as we think about kind of INT and the path to approval and kind of have you had any feedback in the design of that clinical trial that perhaps provided some recommendations that weren't followed? Additionally, kind of will it be you or Merck taking that file forward? And kind of can we assume that CBA will be the FDA group that will assess that particular file? Thank you so much.
Management: Yeah, thank you for the questions. So first on the phase three trial design for our flu vaccine, you're correct, and your memory's right. More than 50% of the population in the study, but it was stratified that at least 50%, would be over the age of 65. We also had a very large population, you know, north of 10%, that was above the age of 75. And as we have presented at medical meetings, and will be available in the upcoming publication, we've seen really strong superior efficacy across all of those populations. In fact, it's remarkably consistent. And as you add frailty or other risk factors to age, or as you look to severe outcomes such as hospitalization, you'll see those point estimates for superiority go even higher and in many cases become even more statistically significant. So we feel very good about that 41,000 person study which, as you just described, or as I just said, has more than 20,000 people over the age of 65 in it. I did describe a separate Phase III study, just to avoid confusion, the P303 study, Part C. That has 3,000 people in it, and that was the study that was head-to-head against gluzone high dose that showed superior immunogenicity.
But the efficacy study, I think, was the one that you were asking about. Now, as it relates to INT, INT is, we're moving forward in a very novel field. And so we've had robust and I would say highly productive engagement with the FDA and truly global regulators around what will be a first of its kind individualized neoantigen treatment. Those dialogues are detailed and I think broadly we are very aligned both ourselves and Merck with those regulators. It is with CBER at FDA, but obviously other offices are involved because it is an oncology therapy of high import. It gets a lot of attention. And I would just say generally we're working closely with regulators to make sure that we're doing everything they want so that they can conduct rapid reviews of the file. Merck is our partner in this. Merck is the sponsor for the Phase III study, so we and they participate in the in those discussions and back and forth, and we each have different responsibilities in our 50-50 joint venture partnership. But the BLA submission, if it goes forward, will be from Merck.
Matthew (Bank of America): Hey, guys. This is Matthew on for Alec. Appreciate you taking our questions. Maybe for RCC, can you walk us through what makes you confident that Phase 2 could be registrational and what hazard ratio or benefit you think would be compelling? And then if you do need to run a Phase 3, curious whether you think Keytruda would be the appropriate comparator arm or whether Keytruda-Belzutaban combo would be preferred pending the LightSpark 22 data. Thanks.
Management: Yeah, that's a great question. You know, one of the exciting things in oncology is it's a fast-moving space, and in individual histology, sometimes the standard of care will evolve, and you're highlighting BALZU for RCC. Look, first, I'd say the Phase II study is blinded, it's powered, and if we see a really significant or profound benefit, you know, we haven't gotten what that hazard ratio would be, but let's assume it's something that would look really dramatic and highly statistically significant. Then it is structured so that it could be a registrational study. But, you know, it wasn't initially intended and powered as that. It's not a phase three study because our primary goal here was we wanted to confirm the hypothesis that INT works well across a range of tumors. And in particular places that we thought there was an opportunity to improve a prawn PEMBRO as a standard of care. Since we started and enrolled that study, there's obviously been the good news of the Balazoo results. Again, that's with our partner Merck. And so, if we see equally great response here for INT, we'll have a conversation with Merck about what we do with INT.
It may mean going forward. It may mean adding it to those because there's always a desire to improve outcomes in cancer. It will entirely depend upon what the data actually says. And so, at this point, we're just excited to look forward to it. But once we have it, the thing that, you know, I think we will be most focused on is, does this confirm the opportunity for INT to work across a range of different cancers and other histologies?
Addy (Evercore): Hi, this is Addy on for Corey. We had a question on the adjuvant melanoma as well. Could you share how do you anticipate use across the broader PD-1, PD-L1 class or primarily only with Pembrolizumab separately as sub-Q PEMBRO and other options become more prevalent? Do you see any impact on regimen selection, logistics, or ultimately uptake for Intuzumab? Thank you for both questions.
Management: So first, I think we will be pursuing a label. Obviously, it's on top of a standard of care in the trial, which is PEMBRO. But we believe that that label could broadly apply to other PD-1, PD-L1s that are approved in the same indication for adjuvant melanoma. Obviously, that will depend upon discussions with regulators, but I think that would follow the precedent of other approaches. And it's in our mutual interest with Merck. We want to see INT be used for as many patients as possible, regardless of the choice of the PD-1 or PD-L1 backbone. Um, the, um, as relates to sub Q, um, you know, I think it, that's really, uh, within the PD one class question. Um, and so how do those antibodies, um, you know, get subbed out for each other going forward? It really wouldn't relate in our mind, uh, to INT, which would be a category of one, uh, and the benefit that INT provides, we believe would apply equally well, although we'll have to see what regulators want to see to see this, but we think the community would agree that would likely apply equally well, whether you're doing a subcutaneous or IV use of a PD-1 antibody. But that's really a question about what they're doing in terms of class share there, because INT will be in a category unto itself.
Management: Ladies and gentlemen, this concludes the Q&A portion of today's presentation. I'd like to turn the call back to Stefan for any further remarks.
Stefan (Title): Well, thank you very much, everybody, for joining. We look forward to speaking to many of you in the coming hours, days, and weeks. Have a great day. Thank you. Ladies and gentlemen, this concludes today's presentation. You may now disconnect.