Bristol-Myers Squibb Company

Bristol-Myers Squibb Company

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Q1 FY2026 · Earnings Call TranscriptApril 30, 2026

Operator

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.

Chuck Triano

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 Boerner, our Board Chair and Chief Executive Officer, and David Elkins, our Chief Financial Officer. Also participating in today's call is Adam Lenkowsky, our Chief Commercialization Officer, and Cristian Massacesi, 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.

With that, I'll hand it over to Chris.

Chris Boerner

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 4.

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 Reblozyl, Breyanzi, Camzyos, Opdualag, KRAZATI, and Cobenfy.

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, Eliquis 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 CELMoDs, iberdomide and mezigdomide, our iberdomide 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 CELMoD to market.

For mezigdomide, 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 CELMoD 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, izalbertecan, we shared positive Phase 3 interim top-line 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 3 China study results for izalbertecan 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 life cycle expansion.

We received approvals for Sotyktu in psoriatic arthritis and Opdivo for two new classical Hodgkin lymphoma indications. We also reported positive Phase 4 switch data for Cobenfy, positive Phase 3 data for Camzyos in adolescents with obstructive HCM, and positive Phase 2 data for Reblozyl in 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 in atrial fibrillation and secondary stroke prevention, Cobenfy in Alzheimer's psychosis, admilparant in IPF, and iberdomide 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 life cycle management opportunities by the end of the decade. Turning to slide 6.

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 Phairis enabling us to design trials more efficiently and [Evanova'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.

David Elkins

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 Eliquis, 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 US.

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 KRAZATI, where the launch continues to progress well with revenues of $163 million. With Opdualag, we delivered another quarter of strong double-digit growth driven by demand globally, where it remains standard of care in first-line melanoma.

Turning to slide 10, Reblozyl delivered 15% growth with performance continuing to reflect solid uptake across first and second-line MDS-associated anemia. In cell therapy, Breyanzi's first quarter growth of 53% reflects its best-in-class profile and continued strong demand across its approved indications in both the US and international markets.

We remain encouraged by Breyanzi's continued momentum and growth prospects. Moving to cardiovascular and immunology on slide 11, Eliquis revenue was approximately $4.1 billion in the quarter, an increase of 13%.

We continue to see strong demand, and given our US 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 Camzyos, revenue in the first quarter nearly doubled to $314 million, benefiting from continued demand growth globally. Now moving to immunology, global revenue of Sotyktu grew 20%.

The recent approval in psoriatic arthritis represents a continued presence in rheumatology while we await our Phase 3 readouts in lupus and Sjögren's disease. I will wrap up our product performance on slide 12 with neuroscience, where Cobenfy 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 pomalidomide, KRAZATI, and Cobenfy 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 the 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 3 cents 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 remains 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 Eliquis 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. 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.

With that, I'll now turn the call back over to Chuck for Q&A.

Operator

We will now begin— We will now begin the question-and-answer session. To ask a question, you may press star then one on your touch-tone 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 two.

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.

Asad Haider

Great. Thanks for taking the question.

Just to open, just given how consequential the clinical readouts at the end of this year are going to be for the company. Cristian, just starting with you, can you just level set us on your confidence in the key programs, specifically for milvexian AF and the Cobenfy ADEPT trials?

Just any quantitative bars for success. 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?

Any framing on potential size of the BD aperture would be helpful. Thank you.

Chris Boerner

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

Cristian Massacesi

Thank you, Asad, for the question. Let me start with the fact that we have a very data-rich 2026 and even probably more '27.

Let me start with what we already achieved, because in MM, I think we had a positive MRD with iberdomide in EXCALIBER in '25, and we are expecting the PFS later this year. As Chris mentioned in his opening remarks, the PDUFA date for this filing is August 17th.

We got Breakthrough Designation, priority review, it's progressing apace. We achieved mezigdomide this year with SUCCESSOR-2, oral presentation at ASCO, really looking forward to show you guys the data.

In MM, we will have a readout also with our Arlo-cel, that is a GPRC5D CAR-T, that is happening later this year. Moving to cardiovascular, milvexian, as you was mentioning, are important readouts.

Both AFib and SSP are continued to be expected by the end of the year. We are recruiting.

The events is an event-driven, and of course we remain blinded. We are recruiting the events as planned, and we had DMC that regularly is reviewing the data and even in the most recent meeting they recommending to continue the studies as planned.

BMS would be the only Factor XI company with Factor XI inhibitor in AFib, of course with the presence also in SSP. This can allow us to continue to lead in the thrombotic space.

Confidence remain absolutely unchanged for milvexian in this space. In neuroscience, we continue to expect the ADEPT-1, 2, and 4 readout by the end of the year.

This is based on we are managing the studies and moving the studies more or less with the same timelines, they are lining up quite nicely. We need two studies probably for an approval.

This is the base case, but for a filing. We will see how the evolution in this space is happening.

The confidence remain unchanged also for Cobenfy. Study design, trial conduction is now completely under control, and of course the reason to believe in Cobenfy in this space are very clear: prior data, the data that we have seen in schizophrenia, and of course the open-label in ADEPT-1 where patient before being randomized receive Cobenfy for 12 weeks give us confidence in potentially bringing this drug in patient with Alzheimer's disease and psychosis.

Last but not least, to me critical readouts this year is admilparant in immunology, in IPF and PPF. This is a novel mechanism, LPA1.

This is an inhibitor that can bring a novel mechanism to patient with this very, very difficult-to-treat disease. Is a first-in-class asset with a very differentiating profile, not only on 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 '27.

Very solid Phase 2 data. I'm very pleased on the execution of the Phase 3 programs.

This is another important therapeutic options. As Chris mentioned, there is much more this year, next year.

I have to say, it's an exciting time to be at BMS.

Chris Boerner

Thanks, Cristian. 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. 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-sized deals.

Chuck Triano

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

Operator

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

Geoff Meacham

Great. Good morning, everyone.

Thanks for the question. Cristian, on pomalidomide, I wanted to check on the cadence of data in, say, the next 6 to 12 months.

Would you wait for more mature data on PFS before you really expand the number of trials, or are you ready to go right now? Then real quick for Adam, just to talk through the KRAZATI dynamics versus Opdivo, and where you're seeing the biggest demand.

Thanks.

Chris Boerner

Thanks, Geoff. Cristian, then Adam.

Cristian Massacesi

Thank you, Geoff, for the question on pomalidomide. Let me start with ASCO.

ASCO will be an important meeting this year for PD-1/VEGF inhibitors. 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 2 data in non-small cell lung cancer in front line as a global data set after the China data we presented previously in other indications.

In few days, the abstract will be released. Our strategy with pomalidomide is replace and expand.

We want to replace PD-1/PD-L1 inhibitors, and we want to expand beyond. We announced, and we deliver seven pivotal 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 and combinability that you have with PD-1/VEGF, PD-L1/VEGF inhibitors, bispecifics. In my view, this is potentially translatable across indications.

Now the next step, at least in our strategy, is novel-novel combinations. BMS has a very rich oncology portfolio.

BioNTech has also an important portfolio of oncology assets, and we started the combination of pomalidomide with these other drugs that represent an enabler for novel regimens, also using some combination with external partner. On our internal side, we started the combination with our izalbertecan ADC, that is an EGFR-HER3 ADC.

You will see data, as Chris was mentioning, at ASCO in esophogeal, triple-negative. It's a very active ADC, and I think with pomalidomide can represent a very powerful regimen.

We started combination with our PRMT5 inhibitor, our novel metelstat, a very dual-type drug. 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 we are very well positioned to make this drug as a potential new backbone in immuno-oncology and generating the next regimens very powerful for cancer patients across indications. Yeah.

Adam Lenkowsky

Geoff, thanks for the question. As relates to KRAZATI, we're pleased with the KRAZATI launch performance.

Our teams are executing well. We're seeing use across multiple tumor types.

We're seeing uptake in our monotherapy indications, as well as in combination treatment, in RCC, in gastric cancer, and in melanoma. We're continuing to hear positive feedback from community oncologists that KRAZATI improves practice efficiency with a three-minute in-office injection, and that patients prefer KRAZATI when offered the opportunity versus the IV formulation.

We've now delivered over 10% conversion from IV to KRAZATI in the US 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 30% to 40% of IV business in the next two years.

Chris Boerner

Thanks, Adam.

Chuck Triano

Great. Can we move to our next question, please, operator?

Operator

The next question comes from Alexandria Hammond with Wolfe Research. Please go ahead.

Alexandria Hammond

Hey, guys. Thanks for taking the question.

On milvexian, given the size and breadth of the Librexia program, 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.

Chris Boerner

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

Cristian Massacesi

Alex, let me start that to tell that we continue to be on track by the end of the year with both AFib and SSP. These trials are event-driven.

We remain blinded. As said, the DMC continue the oversight to the both studies.

We are at a point in which this give us confidence that we are progressing on the right way with both efficacy and safety. Everything's continued as planned.

In AFib, the study will test non-inferiority versus apixaban, and then we will have superiority testing for bleedings. 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?

Adam Lenkowsky

Yeah. Alex, as relates to commercial opportunity, milvexian 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 having both indications. We would expect broad adoption.

As we've 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 DOACs like Eliquis, roughly 40% of patients who should be anticoagulated are either untreated, they're underdosed, or they discontinue treatment, and that's driven largely by concerns around bleeding risk. This leaves a meaningful unmet need across a substantial number of patients.

As a reminder, this study in AFib was designed to demonstrate a superior bleeding profile compared to Eliquis with comparable efficacy. We believe this profile is going to drive significant demand, and it'll be important for both patients and providers.

As Cristian said, we're looking forward to the data readout at the end of this year, and we think this has true blockbuster potential.

Chris Boerner

Thanks, Adam.

Chuck Triano

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

Operator

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

Please go ahead. Hi.

Chris Schott

Great. Thanks so much for the questions.

Just two for me. Maybe first, can you just talk about Camzyos dynamics post your competitor approval, just what are you seeing in the market and just how you're thinking about that evolving?

The second one for me was coming back to the CELMoDs. Now we've kind of seen some of this initial clinical data start to 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.

Chris Boerner

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

Yeah.

Adam Lenkowsky

Thanks, Chris. Camzyos 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 a significant and rapid improvement in symptoms, and we're seeing very low drop-off rates. In fact, we are approaching 25,000 patients now prescribed Camzyos in the US 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.

We also hear consistently that the Camzyos REMS process is very clear, and the infrastructure and workflow that have been established now for four years are very clear, and thus KOLs have shared they'll use the Camzyos dosing and echo regimen at four weeks. We see this as a positive, and why is that?

Because roughly 90% of patients on Camzyos are on the 5 mg starting dose, and it's simply one dose titration to 10 mg. It's 5 or 10 representing 90% of our business, which is effective for the majority of patients.

Camzyos patients feel better in a matter of weeks, where we see from the competition requires multiple titration steps to reach an effective dose. Our teams were well prepared for the launch of aficamten, and we remain confident that we'll be the leader in the space longer term.

As it relates to iberdomide, we're really excited about the launch of Iber, and I know that Chris and Cristian have talked about this. I think there are a few areas that I could point to.

Number one, with iberdomide, 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-burden regimens that can provide a better experience for their patients, and we're confident that iberdomide 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. Our goal is to make both Iber and Mezi foundational in multiple myeloma, replacing Revlimid and Pomalyst 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 Iber and Mezi 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.

Cristian Massacesi

Adam, allow me to step in. Chris, I want to use the opportunity you mention the question on Camzyos, because we received often the question about the non-obstructive HCM plans.

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 with diseases they are affected by that can benefit most from a myosin inhibitor like Camzyos. 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 clinicaltrials.gov while we are progressing this work.

Chris Boerner

Thank you, Cristian.

Chuck Triano

Next question, please, operator.

Operator

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

Evan Seigerman

Hi, guys. Thank you so much for taking my question.

Another one for Cristian. 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 increase your confidence in its potentially successful readout later this year?

Chris Boerner

Cristian?

Cristian Massacesi

Thank you, Evan, for the question. I think your question is referring to AFib specifically, I imagine.

Yeah. In AFib, let me tell you that first of all the data are solidly based on a Phase 2 studies that we run in total knee replacement that is a very good surrogate for antithrombotic drugs.

We learned a lot from Eliquis 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 milvexian was in selecting the dose for AFib.

In that trial, we tested multiple dose levels, and ultimately we landed with 100 mg twice a day, that is a much higher dose, for instance, that we are using in SSP, but is a dose that give us the confidence based all the work that has been done, the modeling and the work then that we were able to bring in the Phase 2 part give us confidence to have at least same level of efficacy than what we expect 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 a head-to-head comparison in a very well-sized study.

We recruited 20,500 patients, very well-powered for non-inferiority margins. We disclosed these margins, of course, they go from 0.8 to 1.3, and we will then, when non-inferiority will be met, test the superiority for bleedings.

We split alpha for major bleeding and no major 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 would be very important in the marketplace.

As said, the study is a fully powered, well-design, and pick, in my view, the right dose to being able to show what the study predefined criteria should meet.

Chris Boerner

Thanks, Cristian. Thanks, Evan, for the question.

Chuck Triano

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

Operator

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

Michael Yee

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.

Just thinking about whether you've taken that into consideration and to what extent you think that impacts 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.

Chris Boerner

Cristian?

Cristian Massacesi

Okay. Thank you, Michael, for the question.

We cannot disclose baseline characteristics and which kind of events we are recruiting. By the way, we remain 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.

We are on track by year end. Is event-driven.

We are in April. We will see later in the year if these event rate will change or not.

For the moment, we are on track for a year-end readout.

Chris Boerner

Thanks, Cristian.

Chuck Triano

Great. Thank you, Cristian.

Next question, please, operator.

Operator

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

Hey.

Akash Tewari

Thanks so much. For your Cobenfy 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 this study, and was it based on any issues you saw with the ADEPT-2 trial conduct? Then just on CELMoDs, can you talk about your confidence on the SUCCESSOR-1 study, which goes head-to-head against Pomalyst, showing a clinically meaningful effect size based on the results you saw on SUCCESSOR-2?

Thank you.

Chris Boerner

Cristian? Yeah.

Cristian Massacesi

Thank you, Akash. The Cobenfy ADEPT-4 decision to go into a biomarker-selected population was based in try to decrease heterogeneity in the patient population.

As ADEPT-2 was a study that was already ongoing at the moment we acquired Cobenfy, 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 that can be done through plasma or radiologically.

I think, of course, this is increase the confidence that the right patients are treated in the trial, even if increase a little bit the operational challenges, because of course we need a predefined number of patients biomarker-positive to run. The screening failures are a little bit higher.

This is doesn't take out any confidence of the potential benefit you can see also maybe in trial like ADEPT-2, 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, and we are not the only one taking this approach in the space.

Going back to your second question on CELMoDs, I think SUCCESSOR-2 was a very good news, not only because, as you mentioned, SUCCESSOR-2 is an add-on study on top Kd, but because came earlier than expected. We hit an interim PFS.

You will see the data at ASCO, but you already know that when you hit an interim PFS means that you hit a bar that is higher what the study was design for. This is answering your question on SUCCESSOR-1.

We believe mezigdomide is a very potent CELMoD, is 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 iberdomide is doing that job.

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. The confidence on SUCCESSOR-1 is high, and of course is a higher bar because it's not an add-on, it's a replacement strategy, but I think the PTS is high.

Chris Boerner

Thanks, Cristian. Let me just also say that I'm glad to hear so many questions on CELMoDs.

The CELMoD program, we're quite excited about. You're going to see exciting data at ASCO on Iber and Mezi.

We shouldn't forget you'll also see data on golcadomide, 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, and it's nice to see these data maturing as they are across each and every one of these programs. It's exciting to see.

Stay tuned for that at ASCO and beyond.

Chuck Triano

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

Operator

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

Louise Chen

Hi. Thanks for taking my questions.

I wanted to ask you, in addition to your ADEPT study for Cobenfy, I know you have several additional potential indications for Cobenfy, and which of those additional indications are you most excited by? Then secondly, you have a lot of different modalities in your cell 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.

Chris Boerner

Cristian, and then Adam, you can provide color commentary.

Cristian Massacesi

ADP, because we believe this is a huge medical need, and we believe Cobenfy can bring benefit based on what we are seeing in schizophrenia. We are focusing our strategy in psychosis, specifically assessing hallucination, delusions, and this is something that we have seen patients 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 the difference, one is biomarker-selected population, the other one not.

We have ADEPT-1, that is more a study that will assess how Cobenfy will avoid relapse. We also design ADEPT-5, we have now four shots on goal in this program, because the base case I was mentioning before is having at least two positive.

Things are changing maybe, and we believe this is an important setting. Cobenfy 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 expecting readouts in 2027.

We are testing Cobenfy specifically in mania in the context of bipolar disorders, and if you think this is a very similar in terms of the productive symptoms that we see in a AD psychosis. Then we have AD agitation.

AD agitation is very related to psychosis because this is one symptoms that we have seen Cobenfy already providing benefit. The confidence is high also for this.

Agitation is coming in 2028 like AD cognition. Cognition is probably a different mechanism.

Psychosis is probably mediated by muscarinic receptor 4, cognition probably by muscarinic receptor 1, but Cobenfy is working on both. This is where the confidence stay.

I would say the Cobenfy, we believe, can bring benefit in controlling this kind of symptoms in Alzheimer, in bipolar patients, and is an anchor asset for our portfolio in neuroscience. I really would like you to start to see how we're building our portfolio in Alzheimer 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.

Adam Lenkowsky

Just to add, Cristian did a great job covering much of our life cycle management program, but from a commercialization standpoint, I would say, stepping back, there are roughly 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. This presents a real significant unmet need where there are no approved treatments today.

We know that antipsychotics have significant safety limitations. They have movement disorders, they carry boxed warnings that are specific to elderly patients with dementia, and they are often treated and used inappropriately rather than treating the underlying psychiatric diseases.

They lead patients with cognitive impairment, falls, and fractures, and these are all really serious issues in long-term care facilities. We believe that Cobenfy 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 Cobenfy is not associated with EPS, sedation, doesn't carry a boxed warning, and in those two areas, ADP and Alzheimer's disease cognition, Cobenfy would be the first and only product approved in those spaces.

Cristian Massacesi

Thank you, Adam. Louise let me go back to your second question on cell therapy.

I could discuss about cell therapy strategy in hematology or in autoimmune disease. I want to focus on autoimmune disease because probably is newer, and I think is important that we explain the strategy that we want to put in place on the development and maybe on the commercial side.

I believe BMS has a very powerful platform in this space, and with one aim: reset the immune system. To reset the immune system, this is the strategy that we want to take, we decided to have a multimodal approach.

This is why we have an autologous, an allogeneic, and an in vivo platform. I have to say, this sets us apart compare many other players in the space.

If you think these products, that can be transformative for patients with autoimmune disease, because if you can eradicate B cells, you can provide benefit to patient with severe or moderate state of disease, but the vision can be to use this one-time treatment before the patient start to have the organs damage by the autoimmune diseases. The most advanced program is zolbetuximab, our autologous CAR-T.

We have two ongoing pivotal studies, one in lupus and one in scleroderma. We have multiple other indications ongoing, and we see a level of activity that is unprecedented.

Then we having clinic now an allogeneic CAR-T that of course can represent a more accessible and scalable approach, because from one donor you can manufacturing a hundred cells, and so this can broaden up the access. The real transformative thing can be in vivo.

We acquire Orbital, an mRNA in vivo platform, where you have the patients that are manufacturing the cells in self where self. This is really can be transformative because it can really broaden up and give scalability in a such broad space like autoimmune disease.

We want to be a player. We want to lead in this space.

I think we are very well set to do that.

Chuck Triano

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

Operator

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

Terence Flynn

Great. Thanks so much for taking the question.

I'll keep it to one. Cristian, appreciate the details on the milvexian 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.

Cristian Massacesi

Maybe I start, and then, Adam, you can step in as you want. Terence, again, the study is designed to show non-inferiority.

Non-inferiority has margins that goes, as I was mentioning, we disclosed these margins, why I can speak about it, they go from 0.8384 to 1.3 something. We believe, and the study and the preclinical and clinical work done in Phase 2 is set to show that the non-inferiority is met to have a similar activity and efficacy versus apixaban.

It is possible that milvexian can have an hazard ratio less than one, but is not needed, because clinically and maybe commercially, the success require to be similar and having a better bleeding profile in major bleedings and clinically meaningful bleedings. This is where the study, I think, is extremely well set and powered to show the non-inferiority and then superiority on the bleeding rates.

Adam Lenkowsky

Just from a coverage standpoint, Terence, what payers consistently tell us is that bleeding, and 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 suggesting that potential of an improved benefit-risk profile will be a strong value proposition, particularly around economic benefits.

Payers aren't necessarily anchored to a specific percentage threshold, but 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.

Terence Flynn

Thanks, Adam. Thanks, Cristian.

Chuck Triano

Great. Let's take our next question, please.

Operator

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

Seamus Fernandez

Great. Thanks for the question.

If I may, just wanted to drill in a little bit on admilparant and the opportunity there, just from a commercial perspective. We're seeing a very robust potential combination market poised to emerge here, but obviously the key is success in clinical programs.

Just wanted to get maybe Cristian, a little bit more of your sense of what are the key risks as we evaluate Phase 2 to Phase 3, and how do you see the opportunity beyond that when we look back at the Phase 2 incorporated a Bayesian analysis from a statistical perspective. There weren't that many patients on background therapy.

Just trying to get a better understanding of how you see the risk-reward heading into the IPF results and the PPF results. Then just for Adam, 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 drop-out rate that patients experience and suffer from versus some of the emerging data sets for other combinations in this setting like the treprostinil data?

Thanks so much.

Chris Boerner

Cristian, then Adam.

Cristian Massacesi

Seamus, let me start with the target. LPA1 inhibition is important because it's working in three dimension in the fibrotic process in IPF and PPF: fibrosis, inflammation, also repair.

This is the novelty of the target, and I think admilparant 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.

There are drugs the patient can use today that have some GI issues, some cough issues, admilparant profile is very different, very differentiated. The conviction on this program is sitting on the Phase 2 results.

In both IPF and PPF, we have more than 60% improvement versus placebo in the lung function decline with 60 mg BID. We tested different doses, and the dose relationship is very clear.

This is another nuance very important that we put in the Phase 3 that give 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, continue to monitor and reviewing the conduction of the study, safety and efficacy, and tell us to continue as planned. We do not see any flag, especially on safety side in terms of hypotension, syncopal events overall in the trial.

Two shots on goal with 60 and 120 in a very well-designed power studies. The Phase 2 and the Phase 3 population are very similar.

The teams did a very good job in ensuring consistency and in trying to have as much as possible in Phase 3 what we did in Phase 2. In your question specifically on the design of the trial, in both trial, in IPF, we stratify based on prior treatments, pirfenidone, nintedanib, or nothing.

We can use as add-on or in patient that don't receive any treatment, and in PPF, there is stratification based on usage or not of antifibrotics. 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.

Chris Boerner

Adam? Yeah.

Adam Lenkowsky

Just quickly, Seamus. We're excited about this program as well.

We believe that admilparant has the potential to play a meaningful role in both IPF and PPF with an improved efficacy and tolerability profile as Cristian 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 alluded to, GI tolerability remains a significant barrier, where practically 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 admilparant 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 unmet needs in the marketplace.

We've got important pre-launch activities that are underway now, and we are very much looking forward to the data readout in the second half of the year.

Chuck Triano

Great. Thanks, Adam.

Operator, can we please take our last question?

Operator

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

Mohit Bansal

Great. Thank you very much for squeezing me in.

I have a question on pomalidomide. Your competitor has signaled that a VEGF/PD-1 compared to an 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 when we compared to chemo, but but with the with the IO combo, it may not be a same situation. How how are you thinking about that given that Bristol is probably the only company with two IO combos on the market and you've seen data for both both both both LAG-3 as well as CTLA-4 on top of PD-1?

How are you thinking about this sort of regression from PD-1 to from PFS to OS given in the context of VEGF/PD-1? It's kind of an important investor debate right now.

Thank you.

Chris Boerner

Cristian?

Cristian Massacesi

Thank you, Mohit, 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 mechanism 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. There is another important learning that we are having everyday with these drugs.

Our pomalidomide is a safe drug. The safety is very predictable.

The combinability is very high. We know VEGF is impacting PFS.

This is what also you are mentioning. I think that we will see where the data are maturing, we will see even in few weeks at ASCO, what this PFS improvement can translate in terms of OS.

My base case, Mohit, is that if I have a drug that give me a good PFS gain and statistical significance OS gain that would be without increasing the safety in dramatic way, this 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 translate in OS because here we have the IO component.

We still don't know how much the VEGF part of the drug is giving us the upside for the IO. It's possible actually that this is give us an uplift also for OS.

I'm excited by this bispecifics. I'm excited very much about pomalidomide 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.

Chris Boerner

Thanks, Cristian. 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's going to strengthen the growth profile for the company, and operating consistently with financial discipline. 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. With that, thanks for joining us today, and as always, the team is available for follow-ups.

Have a good rest of the day.

Operator

The conference has now concluded. Thank you for attending today's presentation.

You may now disconnect.