Bristol-Myers Squibb Company

Welcome to the Bristol-Myers Squibb first quarter 2026 earnings conference call. All participants will be in a listen only mode. Should you need assistance, please signal a conference specialist by pressing the star key followed by zero. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star then one on your telephone keypad. To withdraw your question, please press star then two. Please note this event is being recorded. I would now like to turn the conference over to Chuck Triano, Senior Vice President and Head of Investor Relations. Please go ahead.

Thank you and good morning, everyone. We appreciate you joining our first quarter 2026 earnings call. With me this morning with prepared remarks are Chris Berner, our board chair and chief executive officer, and David Elkins, our chief financial officer. Also participating in today's call is Adam Lemkowski, our chief commercialization officer, and Christian Massachese, our chief medical officer and head of global drug development. Earlier this morning, we posted our quarterly slide presentation to bms.com that you can use to follow along with Chris and David's remarks. Before we get started, I'll remind everybody that during this call, we will make statements about the company's future plans and prospects that constitute forward-looking statements. Actual results may differ materially from those indicated by those forward-looking statements as a result of various important factors, including those discussed in the company's SEC filings. These forward-looking statements represent our estimates as of today and should not be relied upon as representing our estimates as of any future date, and we specifically disclaim any obligation to update forward-looking statements, even if our estimates change. We'll also focus our comments on our non-GAAP financial measures, which are adjusted to exclude certain specified items. Reconciliation of certain non-GAAP financial measures to the most comparable GAAP measures are available at bms.com. Finally, unless otherwise stated, all comparisons are made from the same period in 2025 and sales growth rates will be discussed on an underlying basis, which excludes the impact of foreign exchange. All references to our P&L are on a non-GAAP basis. And with that, I'll hand it over to Chris. Thanks, Chuck.

Welcome and thank you for joining our first quarter earnings call. We delivered a solid Q1 and continue to improve our say-to-do ratio with disciplined execution across the business as we continue to best position the company for long-term sustainable growth. Our strategy remains grounded in three priorities, focusing R&D on life-threatening diseases, driving strong execution across the organization to build momentum in our growth portfolio, and maintaining disciplined, shareholder-friendly capital allocation. We saw progress across all three in the quarter. Let me start by highlighting our performance on slide four. We started off the year with solid results across our key marketed products. In the quarter, growth portfolio sales were up 9% year-over-year with contributions from a broad range of assets including Reblazil, Brianzi, ChemZios, Opdulag, Qvantik, and CoBENV. These are differentiated, durable assets that treat serious diseases and remain early in their life cycles, and they continue to strengthen our foundation for long-term growth. Overall, Our growth portfolio performed in line with our expectations for this quarter. Outside of the growth portfolio, Eloquus performed well and grew in line with the range we provided on our Q4 call. David will provide more details on the financials shortly. Turning to our recent regulatory and clinical milestones, in Q1, we made progress advancing our broad and diversified pipeline. Regarding our cell mods, ibertamide and mesignamide, our ibertamide filing for relapsed or refractory multiple myeloma was accepted by the FDA with breakthrough therapy designation and priority review. with a PDUFA date of August 17th. This is an important step for our protein degradation platform, potentially enabling us to bring the first cell mod to market. For mesigdemide, we reported positive phase 3 interim data from the SUCCESSOR-2 study, demonstrating a meaningful improvement in progression-free survival in patients with relapsed or refractory multiple myeloma. This marks the second positive pivotal readout from our oral cell mod program and further strengthens our conviction in the platform. We will also present the full data at ASCO and are actively planning regulatory submissions based upon the data. For our ADC isobren, we shared positive Phase III interim topline results in patients with previously treated triple negative breast cancer based on a study conducted in China. We will present these exciting data along with the positive Phase III China study results for Isobran in previously treated esophageal squamous cell carcinoma at ASCO. At the same time, we continue to broaden the reach of our in-market portfolio through lifecycle expansion. We received approvals for SOTIC2 in psoriatic arthritis and Obdivo for two new classical Hodgkin lymphoma indications. We also reported positive Phase IV switch data for Cobenfi, positive Phase III data for Chemxios in adolescents with obstructive HCM, and positive Phase II data for Revlozil and alpha-thalassemia. Stepping back, these updates reflect the diversity and breadth of our pipeline, both in terms of therapeutic areas and modalities, as well as continued execution across the business. Moving to slide 5, as we've said, the latter part of 2026 is shaping up to include an increasing cadence of pivotal readouts that are expected to further define and de-risk our long-term growth profile. Among the phase 3 readouts expected late in the year are milvexian and atrial fibrillation and secondary stroke prevention, cobenfi and Alzheimer's psychosis, admilpirant and IPF, and ibertamide PFS data. We anticipate these readouts will help us further diversify and broaden our portfolio and are part of our efforts to deliver more than 10 new medicines and 30 meaningful lifecycle management opportunities by the end of the decade. Turning to slide six, central to delivering on these opportunities and enabling sustained long-term growth are our efforts to drive top-tier R&D productivity. In our development organization, we continue to improve execution across drug development by upgrading talent, streamlining decision-making, and instituting tighter management of core clinical activities. We are also focused on enhancing the quality and depth of our early to mid-stage pipeline. Underpinning these efforts are investments we are making in core R&D infrastructure, including broadening the use of AI tools together with laboratory automation and people trained in the right ways of working. In research and early development, target selection and molecule design can have an outsized impact on long-term value. We've set a target to reach lead molecule identification approximately 50% faster, while applying greater rigor so that only the most differentiated molecules advance. In late development, we're using AI to streamline clinical operations, compress development timelines, and enhance quality oversight. Over time, we expect these efforts to deliver a 30% reduction in cycle times versus just a few years ago. Among others, we have ongoing partnerships with FARO, enabling us to design trials more efficiently, and Ebenova's cost optimizer tool. These ongoing efforts across R&D are top priorities for 2026. The organization's continued focus on financial discipline enables us to make these and other important investments. We remain on track to deliver the remainder of our $2 billion in cost savings from our Strategic Productivity Initiative by the end of 2027. With respect to capital allocation, business development remains an important focus. As always, we will continue to index on opportunities where we add strategic value and where we can deliver attractive returns. As our post-LOE growth profile becomes clearer, we'll naturally place greater emphasis on expanding our early and mid-stage portfolio, to support growth into the 2030s. In summary, based on our performance, we see the business currently tracking towards the upper end of our guidance ranges. Looking forward, we have continued momentum in our growth portfolio, broad potential in our pipeline, and the ability to invest in our business while becoming more focused and efficient in how we operate. With that, I'll turn it over to David.

thank you chris and good morning everyone our performance in 2026 is off to a strong start as highlighted by our first quarter results we delivered solid r d commercial and financial performance while continuing to manage our cost structure our persistent focus on execution has further strengthened our foundation as we position the company for long-term sustainable growth. I will begin with a review of our first quarter results and then discuss our financial outlook for the remainder of the year. Starting with slide 8, total revenue in the first quarter was up 1% year-over-year at approximately $11.5 billion. Our growth portfolio continued to perform well, with global revenue increasing 9%, to $6.2 billion. As Chris mentioned, several products that are still early in their life cycles are driving growth, as we intentionally expand our business across a wider range of key assets. Within the legacy portfolio, we saw solid growth from Eloquus, which was offset by the continued impact of increased generic entry across several other brands. All in, we are very pleased with our results in the quarter as we build upon our objective to reshape and redefine BMS as one of the fastest-growing pharmaceutical companies into the next decade. Turning to product performance on slide 9, starting with oncology. Opdivo revenue decreased 8% to approximately $2.1 billion, with most of this decline coming from the U.S. This was primarily driven by an Opdivo inventory drawdown at the wholesaler level, where inventories are at the low end of the typical range. We continue to monitor whether these levels will normalize over the balance of the year. In addition, we saw continued conversion to Kvantik, where the launch continues to progress well with revenues of $163 million. With Optilag, we delivered another quarter of strong double-digit growth driven by demand globally, where it remains a standard of care in first-line melanoma. Turning to slide 10, Rebizel delivered 15% growth with performance continuing to reflect solid uptake across first and second line MDS-associated anemia. In cell therapy, Breonzi's first quarter growth of 53% reflects its best-in-class profile and continued strong demand across its approved indications in both the U.S. and international markets. We remain encouraged by Breonzi's continued momentum and growth prospects. Moving to cardiovascular and immunology on slide 11, Eloquist's revenue was approximately $4.1 billion and a quarter, an increase of 13%. We continued to see strong demand, and given our U.S. price reduction that took effect at the beginning of the year, we also saw some wholesaler inventory build in the first quarter. We anticipate this build to reverse in the second quarter. Turning to Kamsayas, revenue in the first quarter nearly doubled to $314 million, benefiting from continued demand growth globally. Now moving to immunology, global revenue of CITIC2 grew 20%. The recent approval in cirrhotic arthritis represents a continued presence in rheumatology while we await our phase 3 readouts in lupus and Sjogren's disease. I will wrap up our product performance on slide 12 with neuroscience, where Cabenfi revenue in the first quarter was $56 million, representing continued steady growth. Now let's move to the P&L on slide 13. As expected, gross margin declined 280 basis points in the first quarter to 70.3%, which was primarily driven by product mix. Excluding in-process R&D, operating expenses for the first quarter were $3.9 billion, slightly above the same period last year. As compared to a year ago, the incremental investment related to Pumitimig Qvantic and QBEMFI was largely offset by savings from our strategic productivity initiative. This continues to provide additional flexibility to invest behind these growth-oriented opportunities. Our effective tax rate in a quarter was 18.3%, reflecting jurisdictional earnings mix. Overall, diluted earnings per share was $1.58 for the quarter, which includes a net charge of $0.03 a share related to in-process R&D and licensing income. Turning to the balance sheet and capital allocation highlights on slide 14, our financial position remained strong with approximately $11 billion in cash equivalents and marketable securities as of March 31st. In the first quarter, we generated approximately $1.1 billion in operating cash flow. This quarter's cash flow reflects roughly $1.2 billion in lower net cash collections due to eloquent list price reductions. We expect this to be more than offset later in the year through lower rebate payments. In terms of capital allocation, we continue to take strategic and a balanced approach to deploying our strong cash flows. Business development remains a priority, and we are regularly evaluating opportunities in the therapeutic areas we know best, while continuing to return cash to shareholders through our commitment to the dividend. Now moving to guidance on slide 15. We are reaffirming our financial guidance for the full year of 2026. Based upon the first quarter results and our current projections, we see our financial performance tracking towards the upper end of our established revenue and EPS guidance ranges. We will continue to provide updates as the year progresses. In closing, our strong performance in the quarter reinforces our confidence in our ability to deliver long-term value for our patients and shareholders. And to reiterate Chris's comment, our strategy remains grounded in three priorities. focusing R&D on life-threatening diseases, driving strong execution across the organization to build momentum in our growth portfolio, and maintaining disciplined, shareholder-friendly capital allocation. And with that, I'll now turn the call back over to Chuck for Q&A.

We will now begin the question and answer session. To ask a question, you may press star then 1 on your touchtone phone. If you are using a speakerphone, please pick up your handset before pressing the keys. If at any time your question has been addressed or you would like to withdraw your question, please press star then 2. We ask that you limit yourself to one question. At this time, we will pause momentarily to assemble our roster. The first question today comes from Asad Haider with Goldman Sachs. Please go ahead.

Great. Thanks. Thanks for taking the question. Just maybe just to open, just given how consequential the clinical readouts at the end of this year are going to be for the company, Christian, just starting with you, can you just level set us on your confidence in the key programs, specifically formal vaccine AF and the Coventry ADEPT trials, just any quantitative bars for success? And then related for Chris, how do the timing of these readouts impact the company's BD strategy as you think about the different outcomes that could unfold with the results of each of these readouts? And where do you see opportunity as you scan the landscape ahead of these readouts? And any framing on potential size of the BD aperture would be helpful. Thank you.

Thanks for the question, Azad. Christian, you want to start, and then I'll take the BD question.

Thank you. Thank you, Azad, for the question. Let me start with the fact that we have a very data-rich 2026, and even probably more 2027. Let me start with what we already achieved, because in NIM, I think we had a positive MRD with Iberdomide in Excalibur in 2025, and we are expecting the PFS later this year. You know, as Chris mentioned in his opening remarks, the PDUFA date for this filing is August 17. We got a breakthrough designation, priority review, so it's progressing at pace. We achieved the mesignomide this year with success or two. All representation at ASCO, really looking forward to show you guys the data. In him, we will have a readout also with our Arlo Cell, that is a GPRC 5D CAR-T that is happening later this year. Moving cardiovascular malvexin, as you were mentioning, are an important readout. Both AFib and SSP continue to be expected by the end of the year. We are recruiting the events. It's an event-driven. Of course, we are mind-blinded. We are recruiting the events as planned. And we have the DMC that regularly is reviewing the data, and even in the most recent meeting, they recommend to continue the studies as planned. So BMS will be the only factory-level company with factory-level inhibitor in AFib that Of course, with the presence also in SSP, this can allow us to continue to lead in the thrombotic space. Confidence remains absolutely unchanged for Malvexian in this space. In neuroscience, we continue to expect the ADP studies, ADEPT1, 2, and 4, by readouts by the end of the year. This is based on... very we are managing the studies and moving the studies more or less at the same with the same timelines so they are lining up quite nicely we need the two studies probably for an approval this is the base case but for refining but we will see how the the evolution in this space is happening the confidence remain unchanged also for cobenfi study designs trial conduction is now completely under control. And, of course, the reasons to believe in CoBEMF in this space are very clear. Prior data, the data that we have seen in schizophrenia, and, of course, the open label in ADEPT1, where patients, before being randomized, received CoBEMF for 12 weeks, give us confidence in potentially bringing this drug in patients with Alzheimer's disease and psychosis. Last but not least, to me, critical readout this year is Amilparant in immunology, in IPF and PPF. You know, this is a novel mechanism, LPA1. This is an inhibitor that can bring a novel mechanism to patients with this very, very difficult to treat disease. It's a first-in-class asset with a very differentiated profile, not only on the efficacy side, but also on the safety side. IPF is guided by the end of the year. PPF will be just a few months later, probably beginning in 27. Very solid Phase II data. I'm very pleased on the execution of the Phase III programs. So this is another important therapeutic option. As Chris mentioned, there is much more this year, next year. I have to say, it's an exciting time to be a BMS.

Thanks, Christian. And then, Asad, just on your BD question, Look, BD continues to be a top capital allocation priority for us. It's not impacted by the end of year readouts. We have a very strong late stage pipeline. We certainly don't need to chase deals. But as we've said consistently, if there are opportunities that make sense for us to enhance near term growth, we have the financial flexibility to be in the mix. At the same time, we're building for the long term, and we're going to continue to add to our early and mid-stage pipeline as well. And of course, given the size of those deals, we can certainly do both. Irrespective of phase of development, though, the opportunities we're looking for are in areas we know well scientifically, where we can add clinical and commercial value, and ultimately, we can deliver value to patients and to our shareholders. We're size agnostic, as we've been, and we certainly have the financial horsepower to go after multiple size deals.

Thanks, Chris. Let's take our next question, please, operator.

The next question comes from Jeff Meacham with Citi. Please go ahead.

Great morning, everyone. Thanks for the question. Christian, on Pimitimig, I wanted to check on the cadence of data in, say, the next six to 12 months. And would you wait for more mature data on PSS before you really expand the number of trials, or are you ready to go right now? And then real quick for Adam, just to talk through the QVANTIC dynamics versus Opdivo and where you're seeing the biggest demand. Thanks. Thanks, Jeff, Christian, and Adam.

Thank you, Jeff, for the question on Fumitamin. Let me start with ASCO. ASCO will be an important meeting this year for PD-1 VEGF inhibitors. You know, there are some competitor data in plenary that, of course, increase the confidence in the class. And we are presenting, as an oral, our Phase II data in nosomal cell and cancer in frontline as a global data set after the China data we presented previously in other indications. In a few days, the abstract will be released. Our strategy with Pumitami is replace and expand. We want to replace PD-1, PD-1 inhibitors, and we want to expand beyond them. We announce and we deliver 70 water studies across indications. All of them are ongoing, and all of them are recruiting actively. What is very important, in my view, is also what we are doing beyond the first wave of trials. The confidence, in my view, is becoming more and more tangible in terms of level of activity, a combinability that you have with PD-1 VGF, PD-1 VGF inhibitors by specifics. And in my view, this is potentially translatable across indications. Now the next step in our strategy is novel-novel combinations. And you know, BMS has a very rich oncology portfolio. BioNTech has also an important portfolio of oncology assets. And what we are doing, we are combining now, we started the combination of Pumitamig with these other drugs that represent an enabler for novel regimens. also using some combination with external partners. On our internal side, we started the combination with our IsoBrain ADC, which is an EGFR R3 ADC. You will see data, as Chris was mentioning, in ASCO, in esophageal, in triple negative. It's a very active ADC, and I think with Pumitamig can represent a very powerful regimen. We started a combination with our Pyramidify inhibitor, our , a very drug. So in summary, I have to say that the partnership with BioNTech is moving very well because we are progressing the development of this drug with speed. We think that we are very well positioned to make this drug as a potential new backbone in immunology. and generating the next regimens of very powerful cancer patients across indications.

Yep. Jeff, thanks for the question. As it relates to Kevantic, we're pleased with the Kevantic launch performance. Our teams are executing well. And we're seeing use across multiple tumor types. We're seeing uptake in our monotherapy indications as well as in combination treatment, so in RCC, in gastric cancer, and in melanoma. We're continuing to hear positive feedback from community oncologists that Cuvantig improves practice efficiency with a three-minute in-office injection and that patients prefer Cuvantig when offered the opportunity versus the IV formulation. So we've now delivered over 10% conversion from IV to Cuvantig in the U.S. in just over a year on the market and we're tracking well against our expectations and we remain confident in our expectation that physicians will convert approximately to 30% to 40% of IV business in the next two years.

Thanks, Adam. Great. Can we move to our next question, please, after her?

The next question comes from Alexandra Hammond with Wolf Research. Please go ahead.

Hey, guys. Thanks for taking the question. On nalvexian, given the size and breadth of the labrexia program, it seems like there's probably a rich set of outcomes between a clean win and miss. Can you help us think through how you'd approach a subgroup analysis, particularly for patients where the risk-reward calculus might be more favorable for factor XI, and to the extent that the top line doesn't meet that primary endpoint cleanly? Is there a path where a specific patient population still supports a meaningful commercial opportunity? Thank you.

I'll have Christian take that, and then Adam, you can add any color commentary as you need to.

I mean, Alex, let me start with that. to tell that we continue to be on track by the end of the year with both AFib and SSP. You know, these trials are event-driven. We remain blinded. As I said, the DMC continues the oversight to both studies. We are at a point in which this gives us confidence that we are progressing on the right way with both efficacy and safety. Everything is continuous plan. You know, in AFib, the study will test non-inferiority, that's the Apixaban, and then we will have a superiority testing for bleeding. Based on what we have seen in other trials recently, And based on the expectation and how we size and power the study, I think we are very much on track with both the endpoints to show non-inferiority and superiority in bleedings.

Adam? Yeah, Alex, as it relates to commercial opportunity, the vaccine represents a significant opportunity commercially. There's a need for a medicine with low bleeding risk both in AFib and in SSP, and we think there's a significant advantage to having both indications we would expect for adoption. As we talked about previously, fear of bleeding continues to be the main reason why physicians hold back from utilizing factor Xa's in more patients. And despite the highly effective dose, like Eliquis, roughly 40% of patients who should be anticoagulated are either untreated or you're underdosed or they discontinue treatment. And that's driven largely by concerns around bleeding risk. So this leaves a meaningful unmet need across a substantial number of patients. And as a reminder, this study in AFib was designed to demonstrate a superior bleeding profile compared to Eliquis with comparable efficacy. So we believe this profile is going to drive significant demand and will be important for both patients and providers. And as Christian said, We're looking forward to the data readout at the end of this year, and we think this has true blockbuster potential.

Thanks, Adam. Great. Let's move to the next question, please.

The next question comes from Chris Schott with J.P. Morgan. Please go ahead.

Great. Thanks so much for the question. Just two for me. Maybe first, can you just talk about Chem's IOS dynamics post your competitor approval? Just what are you seeing in the market and just how are you thinking about that evolving? And the second one for me was coming back to the cell mods that we've, you know, kind of some of this initial clinical data has read out. Can you just elaborate a little bit more the role in the market you see for those products based on these initial data sets, and how much of your excitement here is based more on the future readouts versus what we're seeing initially here? Thanks so much.

Thanks for the question, Chris. Adam, I think you can take it.

Yeah, thanks, Chris. So, Camzada continues to have very good momentum. Again, our commercial teams are executing very well in the field. We are seeing continued strong new patient starts coupled with high persistency rates. Physician and patient feedback are very favorable, and physicians consistently cite the significant and rapid improvement in symptoms, and we're seeing very low drop-off rates. In fact, you know, we are approaching 25,000 patients now prescribed CAMS-IOS in the U.S., with thousands more prescribed internationally. As far as what we're seeing in the field, we've been planning for competition for some time. HCPs continue to reinforce that they see little differentiation. It's still early. Some physicians have started one or two patients on the competition, and they are still operationalizing their own REMS program. But we also hear consistently that the CAM-XIOS REMS process is very clear, and the infrastructure and workflow that have been established now for four years are very clear, and thus TLS have shared they'll use the Camxios dosing and echo regimen at four weeks. So we see this as a positive, and why is that? Because roughly 90% of patients on Camxios are on the five milligram starting dose, and it's simply one dose titration to 10 milligrams, so it's five or 10 representing 90% of our business, which is effective for the majority of patients. Chemzio's patients feel better in a matter of weeks, where we see from the competition requires multiple titration steps to reach an effective dose. And so, you know, our teams were well prepared for the launch of africanthin, and we remain confident that we'll be the leader in the space longer term. So as it relates to, you know, to ibertamide, you know, we're really excited about the launch of of Iber, and I know that Chris and Christian have talked about this. And so I think there are a few areas that I can point to. Number one, with Ibertamide, this is an area that we know very, very well in multiple myeloma. We see that for multiple myeloma, it's a highly competitive, it's a fragmented market, but there remains a need for more effective and safe options that can address the majority of patients, particularly those patients who are treated in the community setting, and that's 70 to 80% of patients. When we hear from physicians, they're excited about oral, low burdensome regimens that can provide a better experience for their patients, and we're confident that Ibertamide will provide a balance of high potency, manageable toxicity, combinability with daratumumab, with the convenience of an oral treatment that amplifies the efficacy of IMID-based regimens. So our goal is to make both Iver and Mezzi foundational in multiple myeloma, replacing Revlimid and Pomilus in second line over time in the community, longer term serving as partners for T-cell redirecting therapies and cell therapy. We know the work that we need to do to establish both Iver and Mezzi in the market, and we're very excited to bring both of these important medicines to patients because we believe this is a real attractive commercial opportunity.

Adam, allow me to step in. Chris, I want to use the opportunity you mentioned, the question on Camzayus, because I received, we received often the question about the non-obstructive HCM plants. I think, first of all, let me start that the level of benefit expected in non-obstructive is different than in obstructive because the heterogeneity of patients and diseases is much higher. That said, we have learned a lot from Odyssey. We know better who are the patients and which diseases they are affected by that can benefit most from a myosin inhibitor like Amxios. So I want to announce that we are planning now to run a new, more focused study in non-obstructive HCM. And then, of course, the detail of it will be highlighted in clinicaltri.gov while we are progressing this work.

Thank you, Christian. Next question, please, operator.

The next question comes from Evan Seibergen with BMO Capital Markets. Please go ahead.

Hi, guys. Thank you so much for taking my question. And another one for Christian. So you really inherited the design and kind of the Milvexian trials. Can you walk me through the aspects of the trial design, patient selection that, you know, increased your confidence in a potentially successful readout later this year? Christian.

Thank you, Evan, for the question. I think your question is referring to AFib specifically, I imagine, because SFP, yeah. So in AFib, let me tell you that, first of all, the data are solidly based on a phase two study that we ran in total knee replacement. that is a very good surrogate for antithrombotic drugs. We learned a lot from Eloquist in that space, and we know the predictivity value of that kind of population for antithrombotic agents. I think the very elegant and refined work that has been done with Merdexian was in selecting the dose for AFib. That was, in that trial, we tested multiple dose levels and ultimately we landed with 100mg twice a day. That is a much higher dose, for instance, that we are using in SSP. But it's a dose that gave us the confidence based on the work that has been done, the modeling and the work that we were able to bring in in the Phase 2 part. give us confidence to have at least a same level of efficacy than what we expected with apixaban, preserving, of course, the bleeding value. Going specifically to your question, the design of the study is to be able to show a non-inferiority versus apixaban in an end-to-end comparison. In a very well-sized study, we recruited 20,500 patients, very well powered for an inferiority margin. So we disclose these margins. Of course, they go from 0.8 to 1.3. And we will then, when an inferiority will be met, test the superiority for bleedings. We test, we split alpha for measured bleeding and non-measured clinical relevant bleedings. Because I want to link what Adam was telling. This is a major problem in the clinical setting. And being able to show that the drug provide benefit in terms of decreasing the bleedings will be very important in the marketplace. So as said, the study is fully powered, well designed, and pick, in my view, the right dose to being able to show what the study predefined criteria should meet.

Thanks, Christian. Thanks, Evan, for the question.

Let's move to our next question, please, operator.

The next question comes from Michael Yee with UBS. Please go ahead.

Thank you. Following up on the design of the Milvexian study, if you take a look at the recent AFib results, you can see that the stroke rates are quite historically a lot lower than they were back in the original days of Eliquis. So just thinking about whether you've taken that into consideration and to what extent you think that impacts the the study design, and whether you think that there's any chance that the study results will ultimately end up in 2027, which could end up being more positive for you than in 2026. Thank you. Christian?

Okay. Thank you, Michael, for the question. You know, we cannot disclose baseline characteristics and which kind of events we are recruiting. By the way, where am I blinded, of course, to the study. What I can tell you, again, is that the AFib study, LibreXia study, has the right sample size and, of course, has a predefined number of events. We are recruiting the events as expected, and the events' predefined number is for efficacy and, of course, for safety. So we are on track by year-end is event-driven. We are in April. We will see later in the year if this event rate will change or not. For the moment, we are on track for an year and readout.

Thanks, Christian. Great. Thank you, Christian. Next question, please, operator.

The next question comes from Akash Tiwari with Jefferies. Please go ahead.

Hey, thanks so much. So for your CABENFI Alzheimer's psychosis studies, you have several trials, but I know ADEPT-4 requires patients to have a confirmed Alzheimer's diagnosis using both imaging and blood-based biomarkers. Can you talk about why you added that criteria for the study, and was it based on any issues you saw with the ADEPT-2 trial conduct? And then just on cell mods, can you talk about your confidence on the SUCCESSOR-1 study, which goes head-to-head against POMLIS, showing a clinically meaningful effect size based on the results you saw on SUCCESSOR-2? Thank you. Christian?

Yeah. So, thank you, Akash. The COBENFI ADEPT4 decision to go into a biomarker-selected population was based in a try to decrease the heterogeneity in the patient population. As you know, ADEPT2 was a study that was already ongoing in the moment we acquired COBENFI. And we wanted to have a more predefined patient population to be recruited into an Alzheimer's disease psychosis setting. This is why we took this approach of biomarker positivity. This can be done through plasma or radiologically. And I think, of course, this increases the confidence that the right patients are treated in the trial, even if increase a little bit of the operational challenges because, of course, we need a predefined number of patients biomarker positive to run. So the screening failures are a little bit higher. This doesn't take out any confidence of the potential benefit. You can see also maybe in trial like ADEPT2 where we do not have a biomarker positive study because ultimately you treat symptoms. but give more confidence that you have Alzheimer's patients. This is the main reason. We are not the only one doing this, taking this approach in this space. Going back to your second question on CellMoth, I think Successor 2 was a very good news, not only because it, and as you mentioned, Successor 2 is an add-on study on top of KD. but because it came earlier than expected. We eat an interim PFS. You will see the data at ASCO, but you already know that when you eat an interim PFS, it means that you eat a bar that is higher, according to what the study was designed for. This is answering your question on successor one. We believe mesignomide is a very potent cell mode. It's more potent than iberdomide, for instance, is a drug that can be very well combined with the standard of care regimens that we see, a little bit less with anti-CD38. This is why abirdomide is doing that job. But I believe that the level of efficacy we have seen and the design of the study let us believe that this drug can be better than Revlimid and pomalidomide. So the confidence of successful one is high. And, of course, it's higher bar because it's not an ad-on, it's a replacement strategy. But I think the PTS is high.

Thanks, Christian. And let me just also say that I'm glad to hear so many questions on cell mods. The cell mod program we're quite excited about. You're going to see exciting data at ASCO on iBurn Mezzi. We shouldn't forget you'll also see data on golcotomide, which continues, in my view, to be a sleeper in the program just because of the high-quality data that we've seen thus far. You'll see more of that data at ASCO. Of course, behind this, we've got additional degraders, BCL6-LDD, ARLDD, and this program and this platform is quite deep. It's nice to see these data maturing as they are across each and every one of these programs. So, it's exciting to see. So, stay tuned for that at ASCO and beyond.

Thanks, Chris. Let's take our next question, please.

The next question comes from Louise Chen with Scotiabank. Please go ahead.

Hi. Thanks for taking my questions. I wanted to ask you, in addition to your ADP study for Coventry, I know you have several additional studies. potential indications for Coventry, and which of those additional indications are you most excited by? And then secondly, you have a lot of different modalities in your self-therapy, franchise, and pipeline, and how do you see these all coming together to give Bristol a more comprehensive hold on the market? Thank you.

Christian and then Adam, you can provide color commentary.

So ADP, because we believe this is a huge medical need, And we believe a co-benefit can bring benefit based on what we have seen in schizophrenia. You know, we are focusing our strategy in psychosis, specifically assessing hallucination delusions. And this is something that we have seen a patient really having an improvement in schizophrenia. We wanted to have multiple shots on goal. This is why we have ADEPT-2 and ADEPT-4 that are similar studies with a difference. One is biomarker-selected population, the other one not. And we have ADEPT-1 that is more a study that will assess how cobalt will avoid relapses. But we also designed ADEPT-5. So we are now four shots on goal in this program because the base case I was mentioning before is having at least two positives. Things are changing, maybe, and we believe this is an important setting. CoBenfic can bring benefit to patients. We want to really have multiple shots on goal. When thinking the other indication, bipolar disorder is the next one in line because we are expecting results in 2027. We are testing CoBenfic specifically in mania in the context of bipolar disorders. And you know, if you think this is very similar, in terms of the productive symptoms that we see in AD psychosis. And then we have AD agitation. AD agitation is very related to psychosis because this is one symptom that we have seen CoBENF already providing benefit. So the confidence is high also for this. Agitation is coming in 2028, like cognition, AD cognition. And cognition is probably a different mechanism. Psychosis is probably mediated by muscarinic receptor 4, cognition probably by muscarinic receptor 1. But cobenfi is working on both. So this is where the confidence stays. So I would say the cobenfi, we believe, can bring benefit in controlling these kind of symptoms in Alzheimer, in bipolar patients, and is an anchor asset for our portfolio in neuroscience. We are building, and we really would like... you start to see how we are building our portfolio in Alzheimer's with a phase 2 asset and multiple phase 1 assets that show the commitment that BMS has for this disease because we want to play in this disease.

Just to add, Christian did a great job covering much of our life cycle management program, but from a commercialization standpoint, I would say, stepping back, there are probably 7 million patients diagnosed with Alzheimer's disease. And roughly 30% to 50% have psychosis, and that's hallucinations and delusions. And the vast majority have cognitive impairment. So this presents a real significant unmet need where there are no approved treatments today. And we know that antipsychotics have significant safety limitations. They have movement disorders. They carry boss warnings that are specific to elderly patients with dementia. And they're often treated and used inappropriately rather than treating the underlying psychiatric diseases. They leave patients with cognitive impairment, falls and fractures, and these are all really serious issues in long-term care facilities. We believe that Coventry has the potential to play a very important role in treating a number of Alzheimer's diseases. Safety becomes increasingly important in an elderly population where Coventry is not associated with EPS, sedation, doesn't carry a box warning. And in those two areas, ADP and Alzheimer's disease cognition, Coventry would be the first and only product approved in those states.

Thank you, Adam. Please let me go back to your second question on cell therapy. You know, I could discuss about cell therapy strategy in hematology or in autoimmune disease. I want to focus on autoimmune disease because probably it's newer and I think it's important that we explain the strategy that we want to put in place on the development, maybe on the commercial side. You know, I believe that BMS has a very powerful platform in this space and with one aim, reset the immune system. And to reset the immune system, this is the strategy that we want to take, we decided to add a multimodal approach. This is why we have an autologous, an allogenic, and an in vivo platform. And I have to say, this sets us apart compared to many other players in this space. If you think of these products, this can be transformative for patients without immune disease because if you can eradicate B-cells, You can provide benefit to patient with severe or moderate state of the disease, but the vision can be to use these one-time treatments before the patient start to have the organs damaged by the autoimmune diseases. The most advanced program is Zolacell, our autologous CAR-T. We have two ongoing pivotal studies, one in lupus and one in scleroderma. We have a multiple altering indication ongoing, And we see a level of activity that is unprecedented. And then we have in clinic now an allogenic CAR-T that of course can represent a more accessible and scalable approach because from one donor you can manufacturing 100 cells. And so these can broaden up the access. But the real transformative thing can be in vivo. We acquired Orbital, an mRNA in vivo platform, where you have the patients that are producing, manufacturing the cells in cell for cell. So this really can be transformative because it can really broaden up and give scalability in such a broad space like with immune disease. So I hope I addressed the strategic. We want to be a player. We want to lead in this space. I think we are very well set to do that.

Thanks, Christian and Adam. Let's move to our next question, please.

The next question comes from Terrence Flynn with Morgan Stanley. Please go ahead.

Great. Thanks so much for taking the question. I'll keep it to one. You know, Christian, appreciate the details on the Milvaxian AFib trial in terms of non-inferiority on the efficacy endpoint, but just was wondering if you could elaborate in terms of what differential it's powered for on bleeds for superiority, or if you don't want to answer that question, what you think is a clinically relevant delta versus Eliquis that would drive reimbursement coverage. Thank you.

Maybe I start, and then Adam, you can step in as you want. So, Terrence, again, the study is designed to show non-inferiority. Non-inferiority has a margin that goes, as I was mentioning, we disclose this margin, why I can speak about it, they go from 0.8384 to 1.3 something. So we believe in the study and the preclinical and clinical work done in phase two is set to show that the non-inferiority is met to have a similar activity on efficacy versus apixabab. It is possible that maldexium can have an hazard ratio less than one, but it's not needed because clinically, maybe commercially, the success requires to be similar and having a better bleeding profile in measured bleedings and clinically meaningful bleedings. And this is where the study, I think, is extremely well set in power to show the non-inferiority and then superiority on the bleeding rates.

Just from a coverage standpoint, Terrence, what payers consistently tell us is that bleeding, particularly major bleeding, is the single largest cost driver associated with oral anticoagulation therapy today. It's why Eliquis has significant share in the market. And payer discussions are suggesting that the potential of an improved benefit-risk profile will be a strong value proposition, particularly around economic benefits. And payers aren't necessarily anchored to a specific percentage threshold. What they're looking for is a clinically meaningful and statistically credible reduction in major bleeds that translates into fewer hospitalizations and fewer events that are clinically and economically important.

Thanks, Adam. Thanks, Christian. Great. Let's take our next question, please.

The next question comes from Seamus Fernandez with Guggenheim Securities. Please go ahead.

Great. Thanks for the question. So, if I may, just wanted to drill in a little bit on at Milforant and the opportunity there. Just from a commercial perspective, you know, we're seeing a very robust potential combination market poised to emerge here. But obviously the key is success in clinical programs. So just wanted to get maybe Christian a little bit more of your sense of, you know, what are the key risks as we evaluate phase two to phase three? And how do you see the opportunity beyond that? When we look back at the phase two, it incorporated a Bayesian analysis from a statistical perspective. There weren't that many patients on background therapy. So just trying to get a better understanding of how you see, you know, the risk-reward heading into the IPF results and the PPF results. And then just for Adam, you know, as you look at the evolution of this market, how are you looking at the impact of the current antifibrotic standard of care and the dropout rate that patients experience and suffer from versus some of the emerging data sets for other combinations in this setting like the Trapostinol data. Thanks so much.

Christian and Adam.

Seamus, let me start with the target. LPA1 inhibition is important because it's working in three dimensions in the fibrotic process in IPF and PPF. Fibrosis, inflammation, and also repair. So this is the novelty of the target, and I think Armin Pernat is the first in class in this space for both IPF and PPF. The goal here is to improve upon efficacy but also to have a differentiated tolerability. You know there are drugs that the patient can use today that have some GI issues, some calf issues, so amiparant profile is very different, very differentiated. The conviction on this program is sitting on the phase two results. In both IPF and PPF, we have more than 60% improvement versus placebo in the lung function decline with 60 milligram BID. And you know, we tested different doses, and the dose relationship is very clear. This is another nuance very important that we put in the phase three that gave me confidence in what we are doing. Because we are running both studies, IPF and PPF, with two doses, 60 and 120. The dose relationship and the benefit of having higher dose was very clear. Deeper efficacy while the dose is increasing. DMC, also for these trials, are continuing to monitor and reviewing the conduction of the study, safety and efficacy, and tell us to continue as planned. So we do not see any flag, especially on safety side, in terms of hypotension, syncopal events, even overall in the trials. So two shots on goal with 16 for 120 in a very well-designed power side. The phase two and the phase three population are very similar. We tried and the teams did a very good job in ensuring consistency and in trying to have as much as possible in phase three what we did in phase two. In your question on the specific design of the trial, in both trials, in IPF, we stratify based on prior treatment, perfenidone and indelamib or nothing. So we can use add-on in patients that don't receive any treatment. And in PPF, there is stratification based on usage or not of antifibrotics. So the studies will answer that question. and the drug can be used on top of standard of care or as a single agent. Very high confidence on how this program has been delivered on the target, execution, and looking really forward to the results.

Adam? Just quickly, Seamus, we're excited about this program as well. We believe that ad nopron has the potential to play a meaningful role in both IPF and PPF with an improved efficacy and tolerability profile, as Christian described. there remains a significant need for improved therapies that slow disease progression, that are well-tolerated, and ultimately help patients manage their disease. As you were alluding to, GI tolerability remains a significant barrier, where approximately 50% to 60% of patients on treatment today are discontinuing therapy by 12 months with current standard of care. And even what we're seeing with the newest approved products, the diarrhea rate is roughly 40%. What we're hearing from our thought leaders is that, at Milperant, has the potential to be foundational as a first-line option and has the versatility of being used in combination, given the expected efficacy and tolerability profile and our needs in the marketplace. So, we've got important prelaunch activities that are underway now, and we are very much looking forward to the data readout in the second half of the year.

Great. Thanks, Adam. And operator, can we please take our last question?

The last question today will come from Mohit Bansal with Wells Fargo. Please go ahead.

Great. Thank you very much for speaking to me. So I have a question on primatomic. So your competitor has signaled that a VEGF PD-1 compared to an IO or a PD-1 may be able to show a minimal regression in hazard ratio when you go from PFS to OS. We saw regression when we compared it to chemo, but with the IO combo, it may not be a same situation. How are you thinking about that, given that Bristol is probably the only company with two IO combos on the market, and you have seen data for both LAG-3 as well as CTLA-4 on top of PD-1? So how are you thinking about this sort of regression from PD-1 to, or from BFS to OS? given in the context of IGP events, kind of an important investor debate right now. Thank you.

Christian? Thank you, Moit, for the question. Let me start on the way we deliver these two mechanisms. I truly believe bispecifics are a better way to deliver two different mechanisms than using two different antibodies because you are much more on target you're much more selective in delivering them and potentially you can decrease also the off-target issues like adverse events. So there is another important learning that we have had, that we are having every day with these drugs. Our Pumitamig is a safe drug. The safety is very predictable. The combinability is very high. So we know VEGF is impacting PFS. This is what also you are mentioning. And I think that we will see, where the data are maturing, we will see even in a few weeks at ASCO, what this PFS improvement can translate in terms of OS. My base case, Moet, is that if I have a drug that gave me a good PFS gain and a statistical significance OS gain that will be without increasing the safety in a dramatic way is good enough. Because then I can use this as a backbone and I can improve even further pairing other mechanisms that can continue to increase the PFS gain and potentially translating even in a better OS. I don't think we can simplify so much like In the past, VEGF inhibitors did not relate in OS, because here we have the IO component. And we still don't know how much the VEGF part of the drug is giving us the upside for the IO. And it's possible, actually, that this gives us an uplift also for OS. So I'm excited by this, by specifics. I'm excited very much about pomitamide. and the plan that we are putting in place because I truly believe this can be the backbone for future regimens for cancer patients across indications.

Thanks, Christian, and thanks, everyone, for the questions. In closing, I just want to come back to where we started. We're doing what we said we would do. We're executing across the business, advancing a really differentiated pipeline that we think is going to strengthen the growth profile for the company and operating consistently with financial discipline and Of course, that discipline enables us to have flexibility to invest in growth, to pursue business development where it makes sense, and ultimately deliver long-term value. There's always more work to do, but the foundation we've built and the momentum we're seeing gives us confidence in the trajectory of the business. So with that, thanks for joining us today. And as always, the team is available for follow-ups. Have a good rest of the day.

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