Bristol-Myers Squibb Company

Welcome to the Bristol-Myers Squibb Fourth Quarter 2024 Earnings Conference Call. All participants will be in 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 fourth quarter 2024 earnings call. Joining 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 are Adam Lankowski, our chief commercialization officer, and Sumit Hirawat, 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. Reconciliations 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 2023 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.

Thank you, Chuck, and thank you all for joining us this morning. As we'll discuss today, 2024 was a year of good execution across multiple fronts. Importantly, our performance last year established as a solid foundation to continue our multi-year journey to achieve top-tier sustainable growth by the end of the decade. I will begin with some comments on our fourth quarter and full-year accomplishments. Then I will speak to the promise we see with COBINFI and the steady cadence of clinical data catalysts that will begin this year, further defining our future growth potential. I will end with an overview of our 2025 guidance. Starting on slide four, we closed 2024 with strong fourth quarter performance, reflecting another quarter of double digit percentage increase for our growth portfolio. In addition, we saw strong performance across key parts of the company and achieved notable commercial and R&D milestones. Looking at the full year, let's turn to slide five. I'm pleased with the progress we have made executing on our multi-year plan. For the year, the growth portfolio delivered double-digit revenue growth led by Brionzi, Chemzios, Reblazil, and Optulag. In the latter part of the year, we re-established our presence in neuroscience with the U.S. approval and launch of CoBinvi, which is the first novel mechanism for the treatment of schizophrenia in decades. We also received U.S. approval of Obdivo-Cuvantic in late December. This new subcutaneous formulation of Novolumab will help extend the reach and impact of our immuno-oncology franchise to patients into the next decade. Throughout 2024, operational excellence and financial discipline were top priorities for us. As part of this effort, we reallocated significant spend towards high potential growth opportunities. achieving most of our targeted $1.5 billion in savings. We expect to capture the remainder this year. Additionally, we put considerable focus in 2024 on improving R&D productivity. As a result, we have been able to accelerate several programs in our late-stage pipeline. Notable examples include ChemZios, where we completed enrollment in the Odyssey non-obstructive HCM study six months earlier than expected and now anticipate top-line results next quarter. With CoBENFI, the ADEPT2 study in Alzheimer's disease psychosis is expected to have a top-line readout in the second half of this year versus our original expectation of 2026. This is due to our focus on accelerating patient recruitment following the acquisition of Karuna. And with our ibertamide Excalibur trial in relapse refractory multiple myeloma, enrollment is complete, and we have an opportunity for a data readout this year, also ahead of schedule, due to the recent addition of MRD as a co-primary endpoint. Looking ahead, we will continue to sharpen our focus on operational excellence. You saw the early steps of this strategy last year. As a continuation of that, we are taking deliberate steps to become a leaner, more focused company and have identified an additional $2 billion in savings. We expect approximately $1 billion of these savings to be realized this year and the remainder by the end of 2027. David will provide more details shortly. These actions are consistent with our strategy of investing in our growth portfolio and promising areas of science while maintaining financial discipline. As I've said, this is a journey, but we're already seeing progress. I'm confident the actions we are taking are the right ones that will further advance our long-term sustainable growth strategy. Turning to slide six, the U.S. approval of Cobenvian schizophrenia was an important achievement in 2024, and the launch is off to a great start. While we're focused on delivering on the schizophrenia indication today, we see the potential for additional benefit to patients and have made strategic investments in a broad clinical development program. We expect to have important data readouts starting this year and every year thereafter for the remainder of the decade. This year, we're initiating seven Phase III studies across three indications, Alzheimer's disease agitation, Alzheimer's disease cognition, and bipolar I disorder. And next year, we plan to begin Phase III studies in autism spectrum disorder irritability. The significant ramp-up in spending on CoBENV illustrates our focus on continuing to invest behind key growth drivers while simultaneously maintaining financial discipline. Moving to slide 7, we are entering a data-rich period with multiple catalysts over the next 24 months across a significant number of assets. In 2025, we have multiple important registrational catalysts, as you can see on this slide, including several that I already mentioned, as well as the COBENFI ARISE study in adjunctive schizophrenia. Then in 2026, we expect to have registrational data for numerous potential first and or best-in-class medicines, including milvexian in acute coronary syndrome and secondary stroke prevention, admalparant in idiopathic pulmonary fibrosis, and mezignomide in multiple myeloma. We also expect to have registrational data for ArloCell, our GPRC5D, CAR-T, and multiple myeloma, and for RAISE101 in GEPNETS. We believe these data readouts will further de-risk the pipeline and provide meaningful insight into the future growth profile of the company. Now, let me give you an overview of our 2025 guidance and how we see this year playing out on slide eight. In terms of the top line, we estimate revenue to be approximately $45.5 billion, reflecting, as expected, the near-term impact of generics across multiple products and the continued strength of our growth portfolio. As it relates to the bottom line, we expect our 2025 non-GAAP earnings per share to be in the range of $6.55 to $6.85. This reflects the expanded savings program I mentioned earlier. David will provide more details on our guidance. Finally, turning to slide nine, BMS is evolving into a fundamentally different company with a clear multi-year plan, strong execution, and an accelerating pipeline. We now have a younger and more diversified growth portfolio. This includes Coventry, which has the potential to be a significant contributor to growth over the coming years. We have a multitude of important data readouts over the next 24 months with the potential to launch 10 or more new medicines and pursue over 30 indication expansion opportunities over the next five years. And we remain focused on the therapeutic areas where we have a long track record of success and delivering transformational medicines to patients. We are confident in the steps we are taking to reshape BMS, and by the end of the decade, we expect to have a transformed portfolio of marketed products driving top-tier sustainable growth. Now, I'll turn it over to David.

Thank you, Chris, and good morning, everyone. I will begin my review of our 2024 financial results, focusing on our fourth quarter performance. I will follow up with the introduction of our non-GAAP financial guidance for 2025 and some important considerations to help you better understand our financial outlook for this year. Our performance in 2024 is marked by focused execution on driving top-line growth, generating strong cash flow, and managing our cost structure. We have entered 2025 with a stronger foundation to deliver on our long-term growth strategy. Starting with slide 11, sales in the fourth quarter grew 9% to approximately $12.3 billion, driven by volume growth across the portfolio and higher inventory levels in the market. Our growth portfolio delivered another strong quarter with sales up 23% and represented slightly more than half of our revenue. Key brands like Rebazel, Brianzi, Camzias, and Optilag all achieved significant growth. Within the legacy portfolio, higher sales of Elecris were offset by the expected impact of increased generic volumes across several other brands, including Revlimid, Abraxas, Sprycel, and Pomalyst. Overall, our performance in the fourth quarter capped off a very good year for our company. making progress in building a foundation for long-term sustainable growth. Turning to product performance on slide 12, starting with oncology, Opdivo delivered solid growth in the fourth quarter, primarily due to higher volume. In 2025, we are focused on conversion and educating the U.S. market on the benefits of Updivo Qventic, and we expect low single-digit growth for this product and Updivo taken together. With Opdilag, we delivered another quarter of double-digit growth driven by demand in the U.S., where it remains a standard of care in first-line melanoma. Ex-U.S. sales benefited from uptake in newly launched markets. Moving to cardiovascular on slide 13, Eliquis delivered over $3 billion in fourth quarter sales. U.S. sales grew 19%, benefiting primarily from continued strong demand and the typical inventory build. Importantly, as you think about the impact to Eliquis from Medicare Part D redesign, Q1 U.S. sales growth will be tempered sequentially due to the implementation of the 10% manufacturer responsibility in the initial coverage phase. The remaining quarters of 2025 should steadily increase, particularly in the second half of the year due to the elimination of the coverage gap. Turning to Kim Zio's, sales in the fourth quarter more than doubled, benefiting from higher demand and a large inventory bill. As a standard of care in obstructive HCM, ChemZyos continued to show strong momentum as evidenced by the approximate 1,300 new patients added to the commercial drug in the fourth quarter. Additionally, we recently received a label update for ChemZyos in Europe to ease the echo monitoring requirements in the maintenance setting for obstructive HCM. Importantly, We're pleased to announce today that we have a PDUFA date in April for a similar easing of the REMS echo monitoring requirements in the U.S. Let's turn to hematology on slide 14. Rebazil delivered more than 70% growth, reflecting solid uptake across first- and second-line MDS-associated anemia patients. Sales in the U.S. benefited from demand and included one-time gross-to-net benefit. Outside the U.S., Rebazil sales more than doubled, driven by demand across newly launched markets in Europe and a strong launch in Japan. in cell therapy brianzi's fourth quarter sales more than doubled driven by its best-in-class profile and strong demand growth across all its approved indications now moving to immunology on slide 15. global sales of tick to grew more than 30 percent u.s sales benefited from higher demand tempered by gross to net impacts from higher rebates associated with expanded access coverage starting in 2025 we've further improved our access position with 80% of covered lines having zero step edits, which will help us drive demand growth. As a result of this improved access position, however, we expect additional headwinds from higher rebates, notably across the immunology franchise. Regarding CertiQ2 specifically, this will temper our reported sales in the first half of the year until demand volume can offset these impacts. I will wrap up reviewing our performance for the quarter on slide 16 with Neuroscience and CoBenfi. CoBenfi sales in the fourth quarter were approximately $10 million and represent roughly two months of sales and initial stocking. And we've seen strong prescription uptake during these early months of launch. Feedback from both patients and physicians has been favorable, highlighting the benefits of CoBenfi's differentiated efficacy and safety profile. Let's now move to P&L on slide 17. As expected, gross margin declined about 240 basis points in the fourth quarter, driven primarily by product mix. Excluding in-process R&D, operating expenses increased approximately 8%, largely driven by R&D investments, partially offset by our ongoing cost savings program. Regarding our operating expenses, we made significant progress during 2024 against our $1.5 billion strategic productivity initiative. As of the end of the fourth quarter, we realized approximately $1.1 billion in savings and expect the remaining $400 million to be realized in 2025. Our effective tax rate for the quarter was 19.9% compared to 14.9% in the prior year, primarily driven by earnings mix. For the full year, excluding in-process R&D charges, our effective tax rate was 18%. Overall, diluted earnings per share were $1.67 for the quarter, and full year diluted earnings per share came in at $1.15. Turning to the balance sheet and capital allocation highlights on slide 18, our financial position remains strong, with approximately $11.2 billion in cash equivalents and marketable securities as of December 31st. We generate strong cash flow from operations of approximately $4.4 billion in the fourth quarter. In terms of capital allocation, we continue to ensure we employ a strategic and balanced approach. Business development remains a priority, as does our plan to pay down debt. As of the end of 2024, we have repaid approximately $6 billion of the $10 billion of debt we committed to pay down relative to our March 31st, 2024 balance. Our capital allocation priorities also include returning cash to shareholders through our commitment to the dividend. 2025 marks our 93rd consecutive year of dividend payments. On slide 19, I'll provide more detail on our expanded strategic productivity initiative that Chris mentioned earlier. Building on the work we did to capture cost savings last year, we identified additional opportunities to streamline operations, further leverage technology, and drive greater efficiency in our ways of working. As a result, we expanded the existing program to include approximately $2 billion of incremental run rate operating expense savings, with approximately $1 billion to be achieved in 2025. and the remainder by the end of 2027. Under this expanded initiative, savings will be driven by changes in organizational design and efforts to enhance operational efficiency, with each accounting for roughly 50% of the targeted savings. Within organizational design, we will continue to optimize and streamline our workforce to better align with the future needs of the business. To further optimize resources and enhance productivity, we will drive operational efficiencies across multiple areas of the business. In contrast to the initial $1.5 billion cost savings program, where savings were mainly reinvested, this expanded program will see the incremental $2 billion in savings drop to the bottom line. Overall, our focus is to become a leaner, more efficient company while investing behind our growth portfolio and promising areas of science. With that in mind, let me walk you through our non-GAAP 2025 guidance on slide 20, starting with revenue. As Chris said earlier, we estimate revenue in 2025 to be approximately $45.5 billion, primarily reflecting the near-term impact of generics across multiple products, and the continued strength of our growth portfolio. We expect an 18% to 20% decline in the legacy portfolio due to the stacking of LOEs and anticipated headwinds from foreign exchange of approximately $500 million. This will be partially offset by higher revenue and continued strong performance of our key growth brands. Now, continuing with our 2025 guidance for certain P&L line items, we expect our gross margin to be approximately 72%, which reflects the impact of product mix. Excluding in-process R&D, we expect total operating expenses to show a meaningful decline to approximately $16 billion, driven by the expanded cost savings program I just mentioned. We anticipate our overall expenses to be more evenly phased throughout the year. Operating margin is expected to be approximately 37% for 2025. We're expecting OINE income of approximately $30 million. And we expect to maintain our tax rate of approximately 18%. Considering these factors, we expect to deliver non-GAAP earnings per share in the range of approximately $6.55 to $6.85. Before closing, let me provide some insight regarding our expected quarterly progression of revenue for 2025. As it relates to quarterly phasing, we expect the first quarter to be impacted by the typical inventory destocking we see each year following the build in Q4, as well as the additional gross-to-net pressures from Medicare Part D redesign, which will be accentuated within Eliquis. As I said earlier, we expect Eliquis revenue for the remaining quarters of 2025 to steadily increase, particularly in the second half. As a result of this, we expect the legacy portfolio to decline approximately 10% to 12% on a sequential basis, reflecting these dynamics and continued generic impacts as previously communicated. However, on a total company basis, we expect the inventory and gross to net dynamics to normalize beginning in Q2, with second half revenues to be higher than the first half of the year. In closing, our strong performance in 2024 has strengthened our confidence in our ability to deliver long-term value for our patients and shareholders. We remain focused on executing our growth strategy and right-sizing our cost structure. We also look forward to multiple data catalysts, which will accelerate over the next 24 months and will de-risk our pipeline and provide more certainty on the future shape of our company. And with that, I'll now turn the call back over to Chuck for Q&A.

Thanks, David and Chris, for the prepared remarks. Allison, could we please poll for questions?

Sure. And we will now begin the question and answer session. To ask a question, you may press star then 1 on your telephone keypad. If you are using a speakerphone, please pick up your handset before pressing the keys. To withdraw your question, please press star then 2. At this time, we will pause for a moment to assemble our roster. The first question today will come from Chris Schott of J.P. Morgan. Please go ahead.

Great. Thanks so much. Just two quick ones for me. First on CoBenfi, it seems like feedback and coverage dynamics are progressing well. Can you just elaborate on how you're thinking about the ramp of the drug from here as we balance, as you highlight, kind of entrenched physician prescribing habits against what seems like a relatively poor standard of care and pretty large unmet need in the space? I'm just trying to get a sense of like the ramp, how you're thinking about it for 25. And the second one is just on the cost program. Once you're done with this incremental $2 billion, should we think about additional cost opportunities as you go through that 2028 LOE cycle, or is this going to really put the company in, I guess, the right place as we think about the longer-term model and longer-term business? So I'm basically kind of thinking about is the 27 run rate kind of a good way to think about this, or is there another step down as we head into Eloquist and Optivo?

Thank you. Thanks for the questions, Chris. I'll have Adam take the first question, then I'll take the second.

Great. Thanks, Chris. So in regards to CoBENFI, we're very pleased with what we're seeing with CoBENFI. We're three months post-launch, and the launch is really off to a strong start. We're now at approximately 1,000 TRXs per week, and we made very good progress achieving our access goals. So for Medicaid and Medicare, we're tracking ahead of our expectations. We've achieved over 90% Medicaid access And over 80% Medicare access, recall those two payers represent over 80% of the covered lives in this category. And as expected, the majority have one-step edit post-generic. We're also making very good progress with commercial payers. The feedback over the last several months has been very positive. There's been a lot of enthusiasm around the efficacy and safety profile of I'm also pleased with the number of trialists that we're seeing since launch, and we have an opportunity to further expand and increase adoption with the roughly 30,000 psychiatrists. As you say, this is the first new mechanism of action in decades in the treatment of schizophrenia, and so we're out with our team educating customers on Coventry's differentiated profile, and we're breaking reflexive prescribing habits, and that's going to take some time. We would expect to see continued strong uptake through 2025, and as we said, with a ramp in the back half of this year. But taken together, we are really pleased with what we're seeing so far, and we plan to make this a very big product for the company over time.

Thanks, Adam. And Chris, with respect to the second part of your question on the cost program, let me say a few things. First, as you think about this cost program, keep in mind that our focus as a company continues to be on investing for growth. That's investing in the products that we have today, investing in the pipeline, both the late-stage pipeline as well as promising early areas of science. And maybe just give you two quick vignettes on that. We plan to initiate seven phase three programs starting this year on CoBENFI, clearly illustrating that we'll continue to invest in our pipeline. And then Adam can speak to this, but we made significant up investments in commercial last year, which explains, we believe, part of the progress that we've made on products like Chemzio, Updevo, and Breonzi. So investing in growth is a priority for us, and that's the top priority. With respect to the cost programs, just a bit of context. As we were executing on last year's program, we cataloged a number of opportunities for us to become a more agile company, to become more nimble and speedy in terms of how we operate. And given where we are on that program, as well as where we are with respect to LOEs, we think that it makes sense for us to capitalize on those opportunities now. So that's really driven the timing of this announcement, and we think it puts us in a good position going forward. With respect to the follow-up to that, which is will there be additional cost-cutting efforts, there I think we're always going to align the organization to the needs of the business. This is an extension of last year's program. It gives us more financial flexibility. That financial flexibility gives us strategic flexibility. But we're always going to be focused on ensuring that we've right-sized the organization and we've got the right level of spend given where the business is.

Thanks, Chris. Alison, can we go to our next question?

Next question will come from Louisa Hector of Barenburg. Please go ahead.

Hello. Thank you for taking my questions. I just wanted to check your assumption for Part D redesign, if you can quantify it in 2025. And then just an update on syndacumab. I don't see it on the slides, but any update on the filing plans there? Thank you.

Thanks for the question, Louisa. I'll have Adam take both of those questions.

Thanks, Louisa. Good morning. As it relates to Part D redesign, there are pushes and pulls. Overall, we're going to see favorability with Eloquist due to the elimination of the coverage gap. And with that, we're not going to see the historical dynamics with Eloquist, where first half sales have been higher than the second half sales. In fact, You know, what we're going to see in Q1 is going to be the lowest quarter of sales for Eloquist. In fact, mid-single-digit sequential growth from Q4 to Q1 globally. And we'll see second-half sales be higher than first-half sales. But for the full year, we expect strong year-on-year growth for Eloquist. So when you look at products like Revlimid, Pomalyst, Durencia, and Camxios, for example, that's going to offset the Eloquist favorability significantly. as we're going to see increasing growth to net pressures starting in Q1 as patients enter the catastrophic phase. And as you know, we're responsible for 20% in the catastrophic phase and 10% in the initial coverage phase. But as we've said previously, we would project this to be roughly net neutral across our portfolio this year. As it relates to syndacumab, given the data that we have seen, we've made the decision not to commercialize syndacumab. And We're going to continue to prioritize investments and opportunities where we have a competitive advantage. We can deliver the highest return for the company in areas where we believe that we have an opportunity to deliver potentially transformational outcomes for patients. We made a similar decision late last year with Zoposia in UC as we saw the unsuccessful trial in Crohn's disease. And based on our competitive position with Zoposia and IBD, we made that decision as well.

All right. Thanks, Adam. Next question, please, Alison.

The next question will come from Jeff Mecham of Citi. Please go ahead.

Good morning, guys. Thanks so much for the question. I had another one on CoBENFI. I know, Chris, you highlighted the expansion opportunities on slide six. I guess, are there others that you could add or accelerate, you know, beyond what you have? I guess the main question is, since the Imrecclidine failure, you know, are there changes to the investment plan that you're contemplating? And then on the policy front, I want to get your perspective, you know, as RFKJ's nomination or a confirmation looks, I think, fairly eminent. What are the potential puts and takes on IRA revisions? Obviously, there's been a lot of chatter on what discounting could look like in the outer years. Thank you.

Sure. I'll take the first part of that question and then turn it over to Samit and Adam, and then I'll come back and talk about the policy bit. Just let me give you a top line on CoBinfi. Obviously, the competitive dynamics and changes on the competitive front haven't impacted the short term on that product. We have always been focused on delivering that product as quickly as possible to patients. However, we do believe that those competitive dynamics provides a more significant long-term opportunity for us. And so we have put a full court press on ensuring that we do everything we can to capitalize on that opportunity in the long term, and that includes accelerating programs where possible. So maybe Salman and Adam want to comment.

Yeah, absolutely true what Chris just said, because if you think about the dual muscarinic mechanism of action that the drug carries, it opens up the door for investigating and exploring many of the dementia-associated psychosis and agitation disorders. So we will continue to explore where the drug could be applied, where additional indications could be added, and how we can accelerate the development of this molecule, and as well as continue to look into our pipeline, what other molecules we can bring forward in the neuropsychiatric space to be able to manage the unmet medical need that exists for these patients at this time.

I'll just add, Sumit, you know, our focus has been on ensuring a successful launch where generics, atypicals have about an 80% market share, and CoBENFI has significant safety and ethical advantage there. As Sumit just mentioned, we see the unique ethical advantages around the three domains of schizophrenia, hitting on positive symptoms, negative symptoms, and cognition due to its unique mechanism of action. So we didn't expect competition from other muscarinics in schizophrenia until late 26, early 27. And the failure of Imrakladine, we have a clear path forward in schizophrenia, and we're excited about the opportunity with Coventry. And we believe that we're going to drive meaningful growth for Coventry really into the middle of the next decade.

On the policy front, maybe just a few things. First, as a company, as you well know, we have a long history of working across both sides of the aisle. We actually look forward to working with the new Congress as well as President Trump's administration, including nominees like RFK, once those nominees obviously are confirmed. Our focus as a company is going to continue to be on policies that strengthen the ecosystem for innovation, that make sure that we're ensuring to address the needs of patients and our employees. Also, I would add ensuring that the FDA has what it needs to fulfill its mission. And so that's going to be our focus as a company. With respect to IRA specifically, I do think there's an opportunity for us to address in the coming administration some of the challenges. As one of the first companies to go through the IRA price-setting process, we've been very clear on concerns that we have with that law, and we see the need to have a number of fixes that will avoid some of the more damaging aspects of the law and some of the more perverse incentives. And I would highlight addressing the bill penalty and addressing the spillover impact as two of the most important areas that we'll be focused on. And of course, there are other policy priorities. But in general, we look forward to working with this administration, and we think we've got some opportunities to do so.

Great. Thank you, Chris. Next question, please, Alison.

And the next question will come from Chris Shibatani of Goldman Sachs. Please go ahead.

Thank you. Good morning. I'm struck by the ability to do several things at the same time while trying to realign your costs and integrate these businesses. There have been several advancements of timelines in terms of data readouts, and there's also been an absence of slippage across integrating aspects of the pipeline that are very important. What are the keys, in your opinion, to being able to deliver on this progress and, in particular, the advancement of timelines?

Maybe I'll start and then turn it over to Samit. I think, Chris, you correctly pointed out there are a lot of moving parts, but I would say one of the reasons that we've been fixated on operational excellence becoming a more nimble and focused organization is making sure that we're staying absolutely focused on those things that are going to drive value to the company and value to shareholders. And so one of those things has been a very laser-like focus on R&D productivity and The work that we've done in that regard has enabled us to accelerate a number of programs that are going to add value for the company. In fact, one of the reasons we have this wave of catalysts that are coming forward over the next 24 months is that we have been focused on ensuring we hit the timelines that we set internally and, where possible, accelerate. And Simon Steen's done a nice job of helping us do that. So, Simon, do you want to comment on specifics?

Yeah, absolutely. Thank you for the question, Chris. As Chris just said, the laser focus is the start, but then again, following the principles we laid out, A few years back, in fact, between Robert and myself, from the research and discovery perspective, the cause of biology to discover the drugs, matching the modality to the mechanisms, and then picking the right diseases. And then after that, accelerating that proof of concept generation. But then if you look at the late development, we broke down the process into multiple pieces and dig deeper into where we were doing well, whereas where were the spaces where we had the opportunity to shorten the timelines. And there we identified several opportunities, and then we started to dig deeper into it. The other thing we did last year is also prioritize the portfolio and made certain decisions what we will pursue versus what we will not pursue. Some assets, some trials were stopped, and then we started focusing on where the most amount of scientific rigor was there to be able to achieve the proof of concept. And once that was achieved, how do we then accelerate that into generation of the data to bring the drug to the patients and to commercialization? All of that has helped, and the examples that I write in front of you, last year, we were able to accelerate and deliver the psoriatic arthritis data early. This year, we'll be able to give chem xylose data early. This year, we'll be able to bring in ADAPT. And now we're working on the next trials as well, as we think about multiple myeloma, LPA1 and IPF, as well as SLE trials for SOTIC2. And of course, that mindset will go in all of these seven trials that we've talked about for CoBENFRI as well. So overall, Very pleased with the progress we've made, but we have a little bit more distance to go, and we'll continue to focus on our portfolio to deliver that.

And just to put a finer point on what Samit said, Chris, we have the potential for 15 or more registrational trials that we'll read out by the end of next year. And so the work that Samit's team is doing to ensure that those are delivered on time is, we think, critical, and we've made good progress in 2024. And as Samit said, we're heads down continuing to execute on that.

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

And the next question will come from Tim Anderson of Bank of America. Please go ahead.

Thank you very much. I have a couple questions. So, the revenue guidance for 25 is about a billion less than consensus. In as much as you've looked at consensus, where are you seeing the biggest differences? Could Cobente be one of those contributors of the delta? And then a longer-term question on earnings. In the past, Chris, you've suggested trough earnings would really be in the very late 2020s. And to me, it has felt like maybe 2028, 2029. Is that still the right way to think about it? And could a product like Coventry or some of these other programs possibly pull that forward?

Thanks for the questions, Tim. Maybe I'll start and then turn it over to David for the first part of your question, then I'll come back for the second part. Look, with respect to how we thought about guidance and the outlook for this year, I think you as well as I think everybody knows the LOE exposure that we have as a company. As expected, this year we're seeing the increased step down on Revlimid as well as the stacking of full-year impacts products like Pomalyst, which lost exclusivity in Europe, as well as in the U.S. price zone of Braxane. And our guidance reflects that. But keep in mind, those are short-term impacts. And the long-term, which is what we're focused on, we feel good about the progression that we're making on the new product portfolio. And then as we discussed just in the last question, we have an exciting set of assets that are going to be reading out that will frame out what the company looks like in the back part of the decade. And then Maybe I'll ask David to fill in some of the specifics on the LOEs and the guidance.

Yeah. Tim, thank you for the question. And just as a reminder, your Bloomberg's for the total company is sitting around 46.2. We're guiding approximately 45.5. If you remember my prepared remarks, so there's a headwind of currency, which we don't believe has been built in, which is around $500 million. So as we look at where we are versus consensus from a revenue perspective, we're broadly in line with where it is. Any minor differences is really as we keep, you know, highlighting is around the legacy portfolio in particular, rather than coming down to two, two and a half, but as well as the other generic impacts that we mentioned on the call. But overall, we feel pretty good where we are versus consensus.

With respect to the trough question, first, I think the way you're thinking about the trough in general is the right way to think about it. As we've said before, we're not going to be giving long-term guidance as a standard course. This reflects the philosophy that we have that we're going to guide to what we and you can hold us accountable for. But what we've also been very clear on is that our focus continues to be on driving top-tier growth exiting this decade. And specifically, that means increasing the velocity of growth that we have in the last couple of years exiting this decade and into the next. So as it relates to trough, we're working to do everything we can to change the timing, the depth, and duration of that. And how we do that is to continue to do more of what we, frankly, did last year, drive growth brand performance, accelerate the pipeline so that we de-risk some of these future catalysts as quickly as possible, use our capital to accelerate growth. Frankly, that's what we did when we acquired Karuna to bring a product like Cobenfi into the portfolio. And in fact, As a result of that and what we see as the long-term potential, we believe we've accelerated the velocity of growth as we exit this decade. So we're going to continue to be focused on finding ways to use capital to continue to accelerate the growth profile. And we're going to become more nimble as a company so we can move quickly to capitalize on those. That's what we're focused on, and that's what we're going to be transparent about our performance against on these calls.

Great. Thank you, Chris. Allison, let's move to the next question.

Our next question will come from Mohi Bansal of Wells Fargo. Please go ahead.

Mohi Bansal Great. Thank you very much for taking my question. My question is regarding Aliquist. So, I mean, there was some thought about Aliquist getting some tailwind because of Pardee redesign given that there is no donut hole now and maybe there is like given the price point, the impact of Pardee redesign may not be a lot. In the context of that, how are you thinking about the growth for this brand for this year? Thank you.

Thanks for the question, Mohit. Adam, do you want to take that?

Yeah, Mohit, thanks for the question. As I mentioned, we're going to see favorability with Eloquist this year in the U.S. due to Part D redesign with the elimination of the coverage gap. And so I talked about the dynamics historically where the first half sales were higher than the second half sales. So we're going to see something very different this year where Q1 sales will be the lowest quarter for Eloquist, and we'll see higher sales in the second half of the year. For the year, we expect strong double-digit growth for Eloquist overall, and we look at where we are positioned in the market in the U.S. We have a market share that continues to grow linearly. Our share in the U.S., NBRX, is roughly 75%, and we know that, you know, with As a relto out of the market, we've got a great opportunity to continue to drive this important brand for the company.

Great. Thanks, Adam. Next question, please.

Next question will come from Trang Han of UBS. Please go ahead.

Hi, guys. Thanks for taking my question. Just two, please. So, firstly, can you just give us some color on the gross margin cadence? for 2025. You touched upon 1Q dynamics, but should we just follow the Revlimid step-downs for the year? Is there any other considerations that we should think about here? And then, just wondering if you can give us any early insights into the access and coverage of Opdivo Quantic, and any thoughts on the uptake for 2025? Thanks.

Thanks for the question, Strong. David, you want to take the first one, and then Adam, you can come in on the second.

No, as you said, you know, the step-down will be mainly driven by Revlimid and POMLIS volumes coming through, with those gross margins being slightly higher than the average. And the only other consideration, obviously, is Eloquist. And I think as, you know, Adam had covered, typically Eloquist is larger in the first half of the year than the second half of the year. This year, that's going to be inverted in that our lowest quarter for Eloquist would be the first quarter. but our sales will be higher in the second half of the year than the first half of the year. So that would be the other consideration as you think through the gross margins of the company in total.

Yes, so as it relates to Avivo Qvantic, these are very early days. The team's out in the field educating healthcare practitioners on the benefits of sub-Q versus IV. As we said previously, we believe physicians will convert at least 30% to 40% of the IV business ahead of our LOE in late 2028. which will extend the franchise into the 2030s. We have seen so far some very positive feedback early on as around usage in adjuvant patients, patients who are treated in combination with Yervoy, like in first-line metastatic melanoma, first-line RCC. The feedback specifically has been positive regarding the three- to five-minute infusion time, really taking off that treatment burden for both physicians and for patients. We've also seen a number of NCCN guidelines updated for your reimbursement question to include Opdivo QVANTIC within just a few weeks after approval. I think the most common question that we're getting is around the reimbursement dynamics here, and we've said conversion from IV sub Q in the first half of the year is going to take some time, mainly due to a temporary J code, which is routine for any new product in this category. Conversion will accelerate in the second half of the year once we transition to a permanent J-code on July 1st. And so we're excited about the launch and what this means for patients, physicians, and, importantly, the durability of our IO franchise.

Great. Thank you, Adam. Let's go to our next question, please.

Next question will come from Evan Siegerman of BMO Capital Markets. Please go ahead.

Hi, guys. Thank you so much for taking my question. One on BD, more specifically, now that we're on this side of the muscarinics debate with Coventry approved and Miraclity not showing any efficacy, can you walk us through kind of your process in determining why you went for Caruna when you wanted to get into schizophrenia? And on kind of a more mechanistic perspective, what's happening with Camzires? We saw a nice step up. What are you seeing in the field that's driving the uptake there? Thank you.

Thanks for the questions, Evan. I'll start and then turn it over to Adam. There's no magic bullet with respect to how you approach business development from our standpoint, but I think there were a few things that we did well with the Karuna acquisition that will frame how we continue to do business development. First, I would note that The senior leadership team of the company owned the decision to move forward with that acquisition. Capital allocation is critically important, as we've discussed. Business development is a top priority for us as a company. It's important as we navigate the back part of this decade. And when you're allocating investor capital at that scale, it's critical that senior leaders take ownership and accountability for it, so we did that. We were very disciplined in the approach. It started with making sure that we really liked the science. We considered multiple options and we zeroed in on the science that was coming out of Karuna as compelling in our view. And beyond that, we felt strongly that this had an opportunity to strengthen our therapeutic areas as well as to give us opportunities to accelerate growth in the back part of the decade. We were very disciplined on the financials. We needed to make sure that we could put a compelling case together that it would add value to the company and ultimately to shareholders. You actually saw how we executed against that post the decision to acquire in that we spent a lot of time with the Heritage Karuna team to fully develop this asset in ways that they were unable to do so. And we think that's important in terms of how we think about the long-term opportunity And maybe the last lesson learned that I'd highlight is we've moved very quickly. And so those lessons, I think, will frame out how we continue to do business development at the company. And then, Adam, do you want to take the second question?

Yeah, Evan. Regarding CAMS IOS, we've seen strong steady and consistent growth from CAMS IOS. As you heard from David's opening remarks, year-end 2024, there were approximately 12,000 patients in the hub and roughly 9,500 patients on commercial drug. So we've established a strong revenue base and we expect continued growth from the expansion of our prescriber base. We're seeing high persistency and duration of therapy and we're continuing to add new patients each and every week. So our focus is now on increasing depth of prescribing in the larger COEs while at the same time increasing breadth in some of the smaller institutions and larger community practices and we're making some good progress there. We also have A couple of things David mentioned. One, we look forward to the PDUFA date that's coming in April. So similar to what we've seen in Europe, our goal is to ease the burden of echo requirements for patients and physicians, and we expect that to open up additional capacity at the COEs. And as a result, physicians will be able to treat more patients. And as you're also aware, we have a data readout in non-obstructive HCM, and we're looking forward to seeing the oddity data in Q2, and that will expand the eligible patient population by about 30% or so. And so that's going to allow CAMS-IOS to have a nice first mover advantage in both indications and across the full spectrum of patients with symptomatic HCM.

Great. Thank you, Adam. Let's take our next question, please.

Next question will come from Akash Tiwari of Jefferies. Please go ahead.

Hey. Hey, thanks so much. So what's the risk around the adjunct schizophrenia trial for Cabenzi? Because we haven't seen a lot of companies run that specific trial, and if they have, they've often failed. So why wouldn't the probability of success for this trial be more like a 50-50 coin flip? And on the Camdias label update, are you aiming for six-month echo monitoring requirements? And if so, how do you think that will help expand access into the community setting? Thank you.

Thanks for the question, Samit and Adam.

Yeah, sure. Thank you for the question. On the injective schizophrenia, I remember where we started off and how patients are treated in the real world. So we obviously have developed the drug as a monotherapy, but these patients were primarily, before they got onto the trial, were receiving the D2 agonist. And thereafter, there was a washout period, patients came on the drug, and then, of course, the trial evaluated the primary endpoint in emergent 1, 2, and 3 at the shorter window. But remember, emergent four and five have now read out with a 52-week follow-up. Many of those patients obviously are also taking concomitant medications in the background. And we've seen that efficacy continue to be maintained as we look towards the 52-week data point as well. So overall, from that perspective, we are confident on the overall safety profile that is emerging on that. And then, of course, from a blinded data perspective, the study has continued at this point. So now we are only a few months away from the readout. for that trial, and of course, on top of that, we'll look at ADAPT trials also reading out beginning at the back end of this year. Coming to ChemZios, just a point that I would like to make is it is very important that we continue to decrease the burden on the sites, on the patients, and the treating physicians. And from that perspective, it was important the data that we've collected from the real world as well as from the clinical trials suggest that the overall safety profile of ChemZios is maintained. many of the patients are treated actually at the lowest doses of 2.5 and 5 milligrams. And considering all of that data is where we approach the health authorities, and you've already seen the action taken in Europe, and now looking forward to the April action as we think about the maintenance for these patients with longer duration in between echoes as we look to the U.S. reviews as well. Adam, if you want to add anything.

Just adding just one bit, you know, again, pointing you to the The European label, the label was updated late last year to reduce the frequency of echo monitoring for patients taking camxios from every 12 weeks to once every six months when patients are in the maintenance phase. So that's after week 12. And what we would expect is not so much in the community, but this will open up additional capacity at the centers of excellence. And as a result, physicians will be able to treat more patients.

Thank you both. Let's move to the next question, please.

Next question will come from Terrence Flynn of Morgan Stanley. Please go ahead.

Great. Thanks for taking the questions. Maybe two for me. David, I just wanted to clarify on the new productivity initiative, should we think about the run rate for year-end 27 as being $15 billion, so an incremental billion off of the 16 now? Just wanted to make sure I understood that correctly. And then on ibertamide, the addition of the MRD endpoint, Did FDA sign off on that? And if so, are you able to get approval on just an MRD endpoint, or do you need follow-up data from the PFS? And anything you can say about what kind of efficacy delta you'd need on MRD? Thank you.

Thanks, Terrence.

David didn't comment. Yeah, this is a thanks for the question. Yes, you have that right. So we said an incremental to $2 billion program, all that dropping to the bottom line. We said a billion of that would drop this year with operating expenses of $16 billion. the further $1 billion achieved by 2027 would get you to operating expenses of 15.

In terms of thinking about abridamide, of course, quite excited that based on the discussions that you probably followed from the ODAC setting perspective, MRD as an endpoint is more and more becoming important because in multiple myeloma, there are multiple lines of therapies that are available, but still no cure available for patients with multiple myeloma. So it is important that we continue to figure out how to accelerate the process of drug development, and that's why newer endpoints are needed. So, of course, we've discussed with the FDA the ability to include MRD as one of the primary endpoints in the clinical trial, and we'll certainly be reading that out most likely in this year. Now, everything in the regulatory world will be dependent on the risk-benefit ratio and the overall magnitude that we'll observe at the end of the day. So, when the data is available, that's when we will engage with the regulators in terms of how they will see that data and what else they would need. Remember, we have not taken out PFS as the second primary endpoint within the trial as well. So, of course, the patients will be followed for PFS and as well as the secondary endpoints, which is overall survival as well. So, we are going to collect maximal data from the clinical trial and engage the authorities based on the magnitude and the timing of the readout.

Thanks, Amit. The only thing, Terrence, I would add, and David got it right with respect to how the cost savings will flow. As I said earlier on this call, keep in mind that as we think about the overall cost structure, as we see compelling opportunities for growth that exist, we're going to make sure that we continue to invest in those. So just keep that in mind as framing all of this discussion around cost.

Right. Thank you. Let's move to our next question, please.

Our next question will come from Courtney Breen of Bernstein. Please go ahead.

Thanks so much for taking my question today, Nicole. Two parts. I think you spoke a little bit about business development in an answer before and referenced it as the top priority from a capital allocation perspective. Can you just talk a little bit about TA alignment, kind of what good looks like, particularly in the context of the organization you have right now? I think last year was a little bit of digesting the deals that you've done quickly, and so wanting to understand kind of how you're thinking about that appetite now and over the course of the year. And then the second was just around kind of co-bent fee and specifically kind of gross to net evolution as we're thinking about this access evolving from kind of initial private pay to more of the government setting to then adding on a little bit of the commercial environment. That would be really helpful to understand how you're expecting that to flow. Thank you.

Both good questions. I'll start and then turn it over to Adam. As we said earlier, and as you reiterated, business development is a top priority for us. Think about that both in terms of partnerships and where it makes sense acquisitions. And the way we think about therapeutic areas is that we're really focused on strengthening our position in the core therapeutic areas that we have today. And that we can do by bringing promising areas of science into the company, as well as looking for assets that can improve the growth profile of the company. And I think you saw shortly after I became CEO in 2023, we did both of those things. What's important and the way we think about it is that we need to like the science and feel that we're the rightful owners of it. The financials have to make sense. And again, we've included in that thinking strengthening the growth profile as a key factor we're considering. And we have to believe that we can drive value for the company and ultimately for shareholders. And As we look across the core therapeutic areas that we have today, as we see opportunities to strengthen our position in those therapeutic areas, the nice thing is that we're in a very strong financial position. And as I said earlier, that financial strength and flexibility gives us strategic flexibility, and that flexibility includes doing business development where it makes sense.

Thank you, Chris. I'll just answer the question around growth to net, Courtney. Thanks for the question. As it relates to growth to net, the brand is going to continue to lean heavily towards the public sector, Medicare and Medicaid. When you think about the evolution of schizophrenia and schizophrenia indications or our Alzheimer's indications, whether it be Alzheimer's psychosis or Alzheimer's cognition, these are patients who are going to be in Medicare or Medicaid Commercial patients are less than 10%. You will see that more commonly in some of the indications such as autism and in bipolar disorder, but the majority of the brand will largely be in the public sector where there are Medicaid best price.

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

Next question will come from Seamus Fernandez of Guggenheim Securities. Please go ahead.

Oh, great. Thanks for the question. So just quickly, on CoBENCI, I was hoping you could talk about the patient experience that you're seeing so far in the field. You know, we know that patients certainly feel better cognitively, but there are questions around the tolerability and the BID dosing. So just interested to know if there's any early signs of, you know, sort of the durability of and how you're managing the GI profile that's been talked about a bit by some thought leaders in that regard. And then the second question is just as we think about the overall kind of multiple myeloma opportunity, just hoping to get a sense of where you think novel oral drugs like ibertamide or mezictamide could appropriately fit within the context of the overall multiple myeloma market. you know, given the availability of generic Revlimid and Pomalyst. Thanks.

Thanks, Seamus. Adam, and then maybe Salma, you can chime in as well.

Yeah, Seamus, thanks for the questions. You know, we've been really pleased with what we're hearing from both physicians and patients. The feedback has been very positive with a lot of enthusiasm on the efficacy and the safety profile. So what we're hearing is, you know, patients are seeing improvement in positive symptoms as early as the first week of treatment and on really the lowest dose, 50 milligrams. And we're also hearing good successes on negative symptoms and, you know, what we were really excited about this asset for, improvement in clarity of thought, improvement of cognition, patients being able to re-engage with their families and even start thinking about going back to work. The AEs, what we've heard from physicians, they're manageable, including the nausea and vomiting because what we're seeing is the majority of physicians in the real world are treating patients at the lowest dose. They're starting with 50 milligrams, they're taking a week or two before they titrate up to the next dose at 100, unlike what you saw in the clinical trials, which moved to 125 milligrams within the first eight days of the trial. So that has been incredibly positively received, and so we're not hearing a lot of the GI top tolerability issues from physicians, but our teams are out there making sure that we're educating on what to expect. As it relates to BID, we know that on average patients are on seven pills per day, and so we're not hearing this as a major objection to prescribing. Last thing I'll mention is we've got an ongoing study looking at taking Coventry with food that will read out this year, so that'll also improve the ease of prescribing for physicians and make it easier for patients as well.

So I'll just take it out from there. And one thing that I would just add on cobenfi. So prior to cobenfi, what drugs were doing was treating the symptoms of schizophrenia, meaning the positive symptoms primarily. With cobenfi, now we are treating schizophrenia, meaning also impacting the negative symptoms. And we are seeing the impact on cognition as we have recently published the data on multiple myeloma switching gears. it's important to understand where the patients are treated and what the drugs are available. If you think about the cell therapies and the T cell engagers or bispecifics, they are to be primarily used in the academic settings, whereas most of the patients with multiple myeloma, especially with the relapsed refractory disease, are being treated in the community setting where it is very difficult to get these therapies with the side effect management and the RANS program that go along with them. And that's where it is very important to continue to develop small molecules which are easy to deliver and can be combined with the standard of care therapies. And that's exactly where ibridamide and mizictamide fit. And you know mizictamide is being compared head-to-head versus pomalidomide, and that's how you replace pomalidomide. And then, of course, there's another trial looking head-to-head, ibridamide versus Revlimid, which certainly we'll read out later, but it is a very important component of the overall development plan. Great. Thanks, Amit. Next question, please, Allison.

Our next question will come from David Rosinger of Learing Partners. Please go ahead.

Yes, thanks very much and congrats on all the updates. Sorry, I have another call coming in here. So, my apologies. They want me on the box to speak. So, I have two questions. First, with respect to the performance in 25, so obviously, The worse that the LOEs perform in 25, the better the setup for the trajectory of growth for the company in 26. But if the loss of exclusivity products perform better than expected, then it makes it a little bit tougher to grow in 26. Could you just discuss that a little bit and provide some initial context for 26? I know that you're not providing guidance at this time. And then second, just with respect to Yervoy, it's been performing very strongly, growing 20%, you know, roughly in the fourth quarter and roughly 20% for full year 2025, sorry, 2024. Can you comment on growth prospects for Yervoy going forward as well? Thank you.

Thanks, David.

David Elkins and then Adam. Yeah, so just on your question around 25 and what to think about heading into 26. First, you know, Revlimid, as we said, we have additional generic entry coming. So about 70% of the market will be supplied by generics. Remember, for Revlimid, full generic entry in January of 26. So we'll be through that by the end of the year. And we have a generic entry of POMELIS next year as well. And the only other headwind that I would mention is is we provided that guidance on IRA, which really took out the worst-case scenario for Eloquist as we head into the IRA in 26 and 27. But really, our focus remains on investing in the growth drivers. You saw the strong execution in that growth portfolio that's now greater than 50% of our business. We exited double-digit growth last year. We feel really good about the position that we're in this year. And then as you think about going into 26 with that growth portfolio, You heard Adam talk about the additional indications in Kenzias and Sictu, as well as Reblazel. And, you know, we got some really important data readouts that we're going to be able to add up to six new NMEs here over the next two years. So that growth portfolio is really coming together. We're adding to that. And then you've heard all the commentary around Clebensi further adding to that growth portfolio. So there's pushes and pulls there. But what's becoming clear is the strength of the growth profile as we go into the second half of the decade here.

As it relates to Yervoy, we're seeing solid demand growth, of course, our core indications, first-line long, first-line RTC, as well as first-line melanoma, where Yervoy is using combination, and that growth is coming both from the U.S. and from our international markets. In the U.S., we continue to see good adoption in the community, and as you know, last year we presented I think it's remarkable 10-year long-term data in first-line melanoma. I think the last thing I'd say is we're also preparing for launches this year in first-line HCC and first-line MSI-ICRC, both in combination with Yervoy, which will help drive Yervoy's performance. We also have an Opdivo Yervoy lung approval that's pending in China. So, taken together, we would expect continued growth from Yervoy in 2025.

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

Next question will come from Matt Phipps of William Blair. Please go ahead.

Thanks for taking my questions. You know, following up on the MRD primary endpoint for the ibertamide trial, is there a time course that the FDA wants as far as how much durability on that MRD? And why not add MRD endpoints to the mezignamide trials? It does look like you already have MRD on the Arlo cell quintessential two. And then similarly, in multiple myeloma, is there a point at which a BECMA What is kind of the profitability breakpoint for a BECMA? And does success of ArloCell really kind of negate the need for a BECMA?

Thank you. Thanks, Matt and Samit and Adam.

Sure. Thank you, Matt, for the question. So for multiple myeloma, look, MRD endpoint is something that is new from the perspective of using as a registration trial endpoint. And that's why we have to continue to follow the patients and provide the durability that in terms of not only MRD, but also overall response rates, CR rate that we will see. And these will be the points of discussion with the FDA as we get into those time points once the magnitude is known for this endpoint, as well as the events occur in the ibertamide trial. In terms of how we are thinking about use of this particular endpoint for other trials, we are continuing to evaluate the potential to leverage an earlier MRD endpoint readout to accelerate the development of our multiple myeloma assets across the board. but it will all depend on the timing, the population, as well as how the event accrual is occurring. Successful studies target a little bit more of a difficult-to-treat patient population, so we'll see how the event occurrence happens, and that may become as one of the studies that we may consider an endpoint as well in the future, but not at this time.

As it relates to abecma, we know multiple myeloma is going to remain a very crowded and competitive space, and there are multiple treatment options available. We remain committed to abecma, but we're going to see continued competitive intensity and competitive pressures. So our focus is making sure that we're optimizing the value of abecma and we're going to remain competitive in the space. As you heard earlier from Chris and David, we're very excited also about GPRC5D, which we believe is going to play a critically important role in the treatment of, you know, post-BCMA CAR-T with a single infusion and an improved safety profile.

Thanks, Adam. Alison, let's take our next question, please.

Our next question will come from Steven Scala of TD Cowan. Please go ahead.

Oh, thank you so much. I have two questions. First, Bristol's second-generation TIK2 completed phase two in psoriasis in August of 2024 but hasn't progressed. So curious what the profile of this agent is, what are plans, and is IBD within those plans? And secondly, Milvexian Phase III readouts in stroke and ACS are expected in 2026, but later in the year. Curious if events are tracking for that 2026 readout, and is there any possibility at all for a 2025 readout for either trial? Thank you.

Thanks, Gene. Summitt? Thanks, Steve, for both the questions. So first of all, for the backup TIC-2, we completed those studies. We have the data. But as you know, we are continuing to progress our overall plans for TIC-2 at this time. And as we spoke earlier, we have to decide within our pipeline where we are going to really focus and prioritize. And at the current time, our focus is truly squarely on TIC-2 and maximizing that opportunity from a development and commercial perspective. So at this time, that TIC-2 is not in the development as you already have stated. From the SSP and ACS readout, events are tracking as well as the enrollment is going really well. We do not expect that readout in 2025. We expect that readout, as we have stated, at the back end of 2026. Great. Thank you, Charlotte. Next question, please.

Next question will come from Kripa Dabarakonda of Truist Securities. Please go ahead.

Hey, guys. Thank you so much for taking my question. I have a campfire question. Congrats on getting the label update in EU. I was wondering with the label change in EU and potentially a change in the US as well, how do you see the peak opportunity now? And with Odyssey data upcoming this year, can you help set expectations for the readout? And then if I can One of the tools we recently spoke to said that there was an issue with drug availability at average pharmacies, is what he said. I was wondering if this is just a one-off, or does it just take time to ramp up availability? Thank you.

I can certainly take those, but thank you. As it relates to the label for CAMS-IOS, as I said, we expect to have a PDUPA date in April of this year, and our goal is to continue to ease the burden of the ECHO requirements for both patients and physicians, and this could open up additional capacity at the COEs. What we are seeing for CAM-Zios, which is consistent and steady growth, we have a very large revenue base that's building, and we continue to expect growth from the expansion of prescribers, and high persistency. Patients are staying on treatment for a very long time because they're feeling better, and so that's going to help with the duration of therapy, and we're focused on continuing to add new patients each and every week. As it relates to the Odyssey readout, maybe if you want to talk a little bit about it, but just as I mentioned, we're looking forward to seeing top-line data in Q2. This is going to add, it's positive, around a third of of patients in HCM and have an opportunity to build upon the success of CAM-Zios with a strong first mover advantage across both indications. And we're certainly looking forward to that data readout. And so I'll turn it to Sumit to talk a little bit more about NHCM, and then I'll quickly answer your CoBEN-FE question.

Yeah, I'll address the Odyssey question very quickly. The paper from a methodology perspective, as well as the baseline characteristics of the patients we just published, in JCC heart failure. So you can certainly pick it up from there. And the primary endpoints of KCCQ and PVO2 are well described, as well as what the statistical methodology is. So, of course, we're looking forward to the readout. And it's just, I think, in the next quarter, we'll be able to see the results, and then we'll share the video.

Yeah, just really quickly on that. You know, we're not hearing that. Our teams are out both with physicians, but they're also at the pharmacies as well. So, you know, I do think that is potentially a one-off We want to make sure that the Coventry is available broadly across the U.S. so patients can get access to this really important product.

Thanks, Adam. Let's go to our next question, please.

Next question will come from Olivia Breyer of Cantor Fitzgerald. Please go ahead.

Hey, good morning. Thank you for the question. What data did you submit to the FDA for the less restrictive CAMS-IS REMS? Did that include anything additional versus what was submitted to EMA? And are you asking the agency for the same two updates that were proposed in the December agenda? I think those are around monitoring frequency and the use of LVOT gradient. And then, Adam, I just wanted to clarify one point you made earlier. You said the European label was updated to reduce frequency, I think you said, from every 12 weeks to once every six months. Just wanted to clarify that I heard that correctly.

Thanks.

Maybe I can start off. Thanks for the question, Olivia. We will not be able to give you the specifics at this time in terms of the asks of the FDA. Certainly, there are several of them, and then we'll see which ones we are able to have a conversation and get from a relief for the patient perspective. And in terms of the data that were submitted, they come from both clinical trials as well as from the real-world evidence, so overall data package was very strong. and we continue to have the dialogue with the regulatory agencies.

Yeah, and Olivia, just to clarify again, the label in Europe was updated to reduce the frequency of echo monitoring for patients taking CAMS-IOs post-week 12. So after week 12, as patients move into the maintenance phase, instead of once a quarter, they're able to now have echoes once every six months.

Thank you, Adam. Next question, please.

Next question will come from James Chen of Deutsche Bank. Please go ahead.

Thank you for the question, guys. I just wanted to follow up on the RISE question. What are BMY's expectations for the PanScore benefit? And then any color on how ADAPT2 will be disclosed? Will the NPIC be top-lined in the PR, and will this be followed by a full data set at a medical congress? Thank you. Comments?

Thank you for the questions. Let me start with the second one for ADAPT. As has been recently done and previously done, at the top line, when it reads out, we will be putting out a press release. But generally, we do not disclose the data. Those will be presented at a medical conference appropriately. And for ARISE, again, the magnitude that we are going to be looking for is going to be the difference between the two arms, as well as the difference that we observe from baseline to the time of readout. So, both of those endpoints are going to be important, apart from the, of course, the secondary endpoints. Right now, we're not commenting on the overall magnitude, but here, even small differences in terms of the points would be very, very important and clinically meaningful, as you know, in the neuropsychiatric space. Great. Thank you, Sean. Next question, please.

Our next question will come from Sean McCutcheon of Raymond James. Please go ahead.

Hi, guys. Thanks for the question. Can you speak to the expectations for the cadence of data for the targeted radiotherapeutic portfolio and prioritization of further investment in BD and internal development following that investment in the infrastructure in that segment? Thanks.

Yeah, from the RAISE bio portfolio perspective, of course, the phase three is already ongoing in GapNet, and this is in the patient population that has already received prior Lutathera, and certainly the phase one data was very strong, and we'll continue to look for not only the response rate, but of course, progression-free survival is going to be important to continue to observe in this one as we look to the readout in 2026. As you know that we are also exploring the activity of this drug in patients with small cell lung cancer in a phase one study. And we recently started a breast cancer program as well. And from the portfolio perspective, we have, we're looking forward to initiation of our phase one program. for GPC-3 as a new target. And then, of course, there's a pipeline behind it in the research space as well.

And the only thing I would add is that we continue to be looking for opportunities to enhance the acquisition of Rays. We believe in this platform, and if it's appropriate and it makes sense for us both financially and scientifically, we would consider business development as well.

Great. Thanks, Chris. Alfred, we'll take our last question, and then we'll turn it to Chris for some closing remarks.

Next question will come from Alexandra Hammond of Wolf Research. Please go ahead.

Thanks for squeezing me in. Just one on Bristol's long-term growth potential. The team has mentioned an underappreciation to the pipeline. Can you apply the key assets you expect to drive revenue looking to the back end of the decade? Maybe your favorite child or two? Thank you.

Well, listen, I'll take that one. We feel great about the pipeline. We have a number of really exciting assets that are coming. We've spoken at length, obviously, about Coventry. Clearly, we also are very excited about our cell mod programs. We have multiple cell mods that we've spoken about today, Ivor and Mezzi, but we haven't spoken about glucotamide. That's a potentially very meaningful product in lymphoma. Molection is important. So, It's very difficult to pick a favorite child here whenever there's such a wealth of opportunity in the late-stage pipeline. And we haven't even talked about the next wave of assets, which includes some really exciting opportunities, including products like CD19 NextT, ARLDD in prostate cancer, as well as others. And by the way, I forgot to mention, in the first wave of assets, LPA1, which is also a very exciting opportunity. A plethora of potential catalysts that will be playing out over the next 24 months, and we look forward to seeing them play out and going from there. So I think with that, we'll close today's call. I appreciate everyone staying on. I know we went a bit long, but hopefully we were able to get to virtually all of the questions. Let's take a step back and maybe summarize where we are. Our priorities as a company, hopefully you've seen on this call, are clear. We're focused on continuing to deliver very strong commercial execution and to deliver on the upcoming pipeline catalyst, some of which we just discussed. We're going to continue to have the ability to enhance value creation through business development and all the while maintaining strong financial flexibility. As I look at 2024, we make very good progress, and I want to recognize our colleagues for all the hard work that they had last year We continue to take decisive action to further right-size our cost structure and invest in future growth. We believe these are important next steps in continuing to execute on the multi-year journey that we're on. And, of course, we remain committed to our overarching goal, which is to reshape BMS to deliver top-tier growth by the end of the decade and, most importantly, generate attractive returns for BMS. So thanks again for tuning in today and as always the team's available for follow-ups and have a good rest of the week.

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