Bristol-Myers Squibb Aktie

Terrific. We are just about in time. So let's keep moving and kick off with the next session, Bristol-Myers, I am very excited to have Cristian Massacesi, CMO and Chuck Triano, SVP and Head of IR. Welcome, both. Thank you for being here. Great to be here.

Great to be here.

So Cristian, I know that there's a lot to talk about, but maybe we can start at 10,000 feet at a high level. We've noted that Bristol has been performing very well from a commercial execution perspective. But I think what investors are most focused on is a very consequential slate of clinical catalysts readouts that are coming up in the fourth quarter and maybe potentially even beyond that in the broader pipeline. And so we're going to try and drill into a lot of the key programs here. But before we do that, I just want to kind of give you the opportunity to make any high-level comments on what you've been spending your time on and what you're most excited about.

Thank you for the question. There are 3, 4 things that I spend -- I joined BMS 10 months ago, most of the time. The first was, as you said, the short-term catalysts and be sure that we have been able to derisk all the studies, the big pivotal studies as much as we can. Because Phase III studies are set in times and during the conduction, condition can change. And Phase III studies can fail for different reasons; operational reasons, study design reasons, patient populations. And not necessarily you can change the science that is underneath the Phase III, but you can correct some of the risks that are intrinsic of every trial.

So the first thing that we did that we are doing now as business as usual is identifying all the potential risk each trial can run into and every trial can be different than the other and then try to mitigate them. And these are from an operational standpoint to statistical standpoint to -- so you can do that. So this gives me confidence that for the next wave of catalyst, at least we did everything in our hands to control the outcome.

And then based on these learnings, make this as a standard way of operating. And of course, you do this not also using technology because of reasons. One thing we are doing is modeling outcomes using AI, using tools, allocating studies regionally based on AI tools that we have. So this is something that is very now entrenched in the way our teams are working.

The second thing I really worked very much is helping is a corporate level to integrate our programs and our drugs into PA and even more disease strategies because this is where I'm very excited with our portfolio. We are focused on oncology, hematology, cardiovascular, immunology, specifically with a focus in immune reset and neuroscience. This is where we want to lead, and we want to continue to build our portfolio. But everything starts from the strategy. And the strategy is the strategy of today, tomorrow and the day after tomorrow. So you cannot simply have a short-term view, but you need to build your portfolio looking what the growth can be going forward.

The last thing was more related on people and try -- for instance, neuroscience is the best example because with the acquisition of Cobenfy, we wanted to be back into this space, but we need to rebuild the units and this require also rebuild the people and bring in the talent. So this is the work that mostly we have done. Of course, a lot of my time is business development. A lot of my time is trying to shape and optimize how we are integrating AI tools into the way we deliver and we make the organization moving along. So -- but it's exciting. I'm very happy about the progress we did.

Well, that's great, Cristian. And maybe we can start peeling away at the onion at a few of these programs, starting with oncology at a high level. I mean, we've just come off of ASCO, very dynamic conference this year, lots of focus again, specifically from a Bristol's perspective on the PD-1 -- PD-L1 VEGF bispecific class. So I guess I want to start with just hearing your updated thoughts on pumitamig in the context of the very encouraging data that was presented at ASCO and overall thoughts on the PD-L1 VEGF class, particularly given the debates around Akeso's HARMONi-6 trial and the issues that were raised by the discussant of the stage when the data was presented, that fueled some investor debate. Are those really substantial concerns? Or is there -- is this just skeptics kind of poke hold in the data?

It's was a good ASCO. Thank you for bringing it up. It was my first ASCO in BMS, but it was an exciting ASCO because I think as BMS, we were able to move from a lot of presentation focused on Opdivo [indiscernible] To presentations showing the next portfolio. Pumitamig was one. We had [indiscernible] we can talk about that.

We have our ADC iza-bren. We have some data also with our PRMT5. So very exciting ASCO because we start to show that there is a portfolio. And in oncology in solid tumor, in hematology, it starts to be -- the start rate. PD-L1 VEGF, important meeting for that class of agents, in my view, a positive meeting, very positive meeting because you start to have more and more data sets that are going in the same direction. Start to see consistently better response rates, consistently PFS benefit. And I start to see some OS data with all the limitations that studies conducted in one specific geographic region may have.

Looking at our data, I am very pleased on what I have seen because we brought at ASCO the third global data set before we presented data in small cell lung cancer and triple-negative breast cancer. At this ASCO, we brought data in first-line non-small cell lung cancer in combination with chemotherapy. First of all, in small cell and triple negative, we have seen consistency from China data and our global data. Here, we had the monotherapy data. This was chemo combo. But what I liked in our data set, first of all, clinically, in squamous and non-squamous, we have seen numerically higher response rate than what you would expect with the pembro chemo combo.

What I have seen also was an outcome specifically exciting in -- not only in PD-L1 positive, but even more in PD-L1 negative with the response rate in the context of a small data set, but numerically much better than what you expect with pembro chemo that in PD-L1 negative is not very much actually. And this was, in my view, corroborated by the preclinical work that we brought to the meeting.

This is a BMS internal work showing why a bispecific delivering PD-L1 and VEGF inhibition can be better than giving the 2 antibodies as a combination. And this is because PD-L1 and VEGFA is in the microenvironment, tumor microenvironment. And when the drug is binding, a cluster is forming and the cluster, the drug and the 2 targets are internalized in the cancer cells. And this is happening independently of the PD-L1 expression.

Even in the context of the PD-L1 negative cancer cells, you see the internalization. When you do some experiment with the PD-1 antibody and bevacizumab, you don't see the internalization of the PD-1 inhibitor. So this is a small piece of evidence that delivering these 2 mechanism as a bispecific can be more selective and ultimately, the VEGF inhibition help PD-L1 internalization and can help actually to increase the activity of PD-L1 because it can revigorate T cell response.

So I believe that this mechanism, these bispecifics and our drug specifically can represent a way forward on improving our PD-1, PD-L1 inhibitors and can help us to go beyond that group of drugs and eventually expand because VEGF can open up other indications like colon cancer.

The program we are doing this in collaboration with BioNTech. The program is moving very, very nicely. We have 7 pivotal studies. We have more than 20 combo study because the next step is not only delivering monotherapy or combo with standard of care, but building the next level of regimens with novel-novel combinations.

With a novel, novel...

The rest of our portfolio step in combo with IDC, combo with other.

And I want to talk about that. But one thing just in the program itself, it seems to me that some of -- one of the themes coming out of ASCO as well as what we've heard through this conference is that some of your competitors are already sort of pressing the accelerator on the speed at which their own programs are moving. For example, Merck said that they are now Phase III ready, which I think surprised some people. So what are the next milestones we should be looking for from pumitamig in terms of just monitoring the progress of your own program?

As I told you, we have 20 studies ongoing. Some of them pivotal will take a little bit longer, but a lot of them are Phase Ib/II. So we will continue to have a constant flow of data, both clinical and also translational data because I want to continue to build more work on the mechanism of action because I truly believe it's differentiated. And I think the data are across tumor types. And again, in the moment in which you will see some of the combo data emerging, it means that probably the next steps as a pivotal study is going to happen.

Okay. Well, let's pivot from there to a theme you already brought up novel-novels, ADCs. Another big focus at ASCO, your partner for iza-bren presented China Phase III data for -- in breast and esophageal cancer. So both met their dual primary endpoints of PFS and OS. So give us an overview of -- at a high level on the global development plans for this for the ADC.

First of all, I am a believer in ADCs because I am a believer in precision medicine. And I think in oncology, I'm a medical oncologist -- in oncology, chemotherapy, radiotherapy are working. The problem is the lack of selectivity and specificity. ADCs and radio-ligands are a better way to deliver these 2 modalities. So iza-bren is a very nicely engineered drug because, first of all, it's a bispecific ADC. It's an EGFR HER3 ADC. EGFR and HER3 are 2 targets that touch most of the solid tumors.

And this drug is specifically higher affinity for EGFR with a very stable linker and shorter life. And actually, what I like is that we don't have any rush because the drug is very stable in the moment in which is injected is internalized and then metabolized. So we see consistent activity across tumor types. Our partner started developing in China some year ago, there are more than 6,000 patients treated in China. So we have a very large data set for efficacy and safety and multiple Phase III.

As you mentioned, there are 3 Phase III positive studies, not anymore one. And in different indications, nasopharyngeal carcinoma, we presented at ESMO, ASCO, we presented esophageal cancer and triple-negative breast cancer later line as a standard chemotherapy. And China only data set in Phase III. And the activity is remarkable, especially because you get the PFS and OS in both trials with very important other ratios.

In triple-negative breast cancer, the PFS ratio is 0.29 from 3.5 months to 8 months. And the OS, the other ratio is 0.6 from 12 months to almost 16 months median OS in second, third-line triple-negative breast cancer. This drug is active. And the safety profile is very predictable. It's mainly hematological toxicity because it's a potent drug, it's a DAR8 ADC. So I think -- but the discontinuation rate is very low. And in the global data set because now we have global ongoing studies, Phase I/II, and we have 3 Phase III studies globally ongoing in EGFR lung cancer and mutant in triple-negative breast cancer and bladder cancer. So it's an important drug in our portfolio as a monotherapy, but it's an important drug specifically when you foresee in combination with pumitamig, for instance, or other player in our drug. So I'm excited about this one.

Okay. Maybe just sticking with ASCO for a second. I want to just talk about -- you had some presentations, obviously, on the CELMoD portfolio in hem/onc. So just maybe to touch on those, iberdomide has a PDUFA date in August in relapsed/refractory multiple myeloma. The presentation at ASCO was an investigator-initiated Phase I focused on the newly diagnosed population. The data seemed encouraging. So what is the path now to getting that integrated into the first line?

It's just talking about iberdomide, let me start with the platform. I think, BMS, we're able to leverage and to expand Celgene platform on protein targeted degradation. I think this is a very powerful platform that is delivering important drugs that can degrade proteins like Ikaros or Aiolos in myeloma and lymphoma, but also other targets that are really key for the cancer cell.

BCL6 is an example that so far was undruggable, and now we have a degrader in lymphoma that can actually work very well in the space. The platform is delivering. We have 11 drugs in clinic, some like ibermeszi (sic) [ iberdomide ], but also golcadomide in Phase III. And -- but other are at the beginning of the development. So I'm very excited about this because these are oral drugs, very combinable, that we can put on standard of care across onco-heme.

Iberdomide specifically, PDUFA date, as you say, August 17, and it would be, hopefully, the first drug approved as an NDA for MRD. But the data we presented at ASCO and other settings that we have shown how combinable is this drug and how can be integrated in the standard of care. This is both for iberdomide and mezigdomide. Our CELMoDs being oral drugs can be added on top of standard of care. And EXCALIBER is on top of dara and dexa. At ASCO, we showed data in the context of a quadruple with dara-velcade and dexa in a patient that newly diagnosed patients not eligible for transplant. And the activity was very good because that was a fixed treatment duration for dara-velcade and dexa and then iberdomide as maintenance, and we have seen a deepen of the response, the MRD response with iberdomide alone.

So it speaks on the quality of these assets, how potent they are, how selective they are and how they can be integrated in the treatment that is becoming more and more fragmented of myeloma as add-on or iberdomide next registrational study will be in post-transplant versus Revlimid as a monotherapy.

And then maybe just quickly on mezigdomide as well. Those Phase III data appeared encouraging in relapsed/refractory multiple myeloma. But interestingly, the data was presented on the back of J&J's MajesTEC-9 study, which was also impressive. So maybe taking a step back, we're hearing some conversations focused on choosing between CAR T and bispecifics in the second line. So where do you see this mezigdomide fitting into the multiple myeloma treatment pipeline?

Well, as I said, myeloma is becoming more and more fragmented diseases, fortunately, because there are more and more options. I think we believe that our CELMoDs will fundamentally replace Revlimid and pomalidomide. And this -- because there are better drugs, more selective engineered for that. And their combinability and they can be integrated in the current standard of care, but also the future standard of care. Actually, just last week, we published 2 papers in Blood showing how mezigdomide can benefit T cells in enhancing their activity and their persistence. So I think this is just the beginning, and we have a great opportunity by integrating CELMoDs in the treatment of myeloma.

Okay. And then Cristian, maybe one last on oncology before we leave -- move on. Just to -- giving you a chance to comment on this, there was some impressive data yesterday on the PRMT5 combination with RAS inhibition. High level, what's your take on that? And how does that influence how you might think about the development of your own PRMT5 program?

It's another drug in our portfolio that I consider a very high priority because it's a good drug. The name is Navlimetostat and it's the PRMT5 working MTAP deletion. Again, I like it because it's precision oncology. We presented some data at ASCO that are more translational work, but also some updated on the monotherapy. And lung and pancreatic cancer response rate are holding 34% in lung, 18% monotherapy, but the durability is very good. Not only the response, durability of stabilization. The drug is doing what it's supposed to do. Then what I really even like more is the combinability. The safety profile on Navlimetostat is very good. It's very mild.

We have the 3 pillars: combo with chemo, we are in Phase II/III in pancreatic cancer, Gem-Abraxane. We know we can combine. Soon, we're going to be in Phase III. And in lung cancer, with platinum doublet. This is the first entry. And then we are combining with pumitamig because it makes sense to combine with PD-1/VEGF plus or minus chemo. And the last is the combination with [indiscernible]. The data you have seen yesterday, very important also for me because derisking the combo. And we know -- we knew that there is a potential synergies of these 2 pathways.

And actually, this preliminary -- very preliminary but promising data showing that I'm very excited about the opportunity. And it's an exciting moment also for a very difficult disease like pancreatic cancer. I mean I'm so happy that these days, we're talking a lot about it because many years that we didn't have anything.

Okay. Well, maybe we can pivot to cardio. And the milvexian AF trial specifically is obviously a big focus. It's something that a lot of investors are paying a lot of attention to with the readout coming up in the fourth quarter and before the end of the year. So I guess just latest framing on your level of confidence on the success of the trial, maybe we can stop there.

Yes. The study was designed on the outcome of a very solid Phase II study in which run in total replacement is good surrogate for outcome, testing a very wide range of doses. I think this is a critically important aspect of the AFib study because, of course, it was very important to find the right dose to ensure to have a similar efficacy because here you go against -- it's not an add-on trial like an SSP, but is a strategy against apixaban. So you need to have a similar activity, maintaining a profile on the bleeding side to ensure a benefit on that side.

And I think the dose of selective 100-milligram twice a day give us that profile and the confidence that we can be a parity on efficacy and then on the safety side, potentially have a benefit. The study is designed as a noninferiority for events, strokes and thromboembolic events and then a superiority for bleeding, major bleedings and non-major bleeding clinically relevant. I'm blinded. No news, good news in my view. DMC continue to monitor the study in a regular and regular way. We have -- we will keep scrutinizing the study conduction, how we are recruiting the events.

These are coming as planned. As you said, we continue to guide by the end of the year. It's an event-driven study. So we need to see next month where are we. the study will be completed and locked when we have the right number of events, the predefined number of events for primary endpoint and non-inferiority and also for the bleeding events, both groups. And then we will see.

So I guess, Cristian, on the bleeding side, what is the expected magnitude of superiority in your view to drive a meaningful displacement of Eliquis?

I think, Chuck, you can -- to me, what I can tell you is that today, there are at least 30%, 40% of patients on Eliquis that because of bleeding risk or because they have experienced bleeding are not receiving Eliquis or not receiving Eliquis at the right dose. So they're suboptimally treated. So this is an important aspect. So this is why we believe that our assessment in measured bleedings that are not so frequent, but are there and no measure bleeding clinically relevant in more patients are both clinically meaningful. Then we will see the outcome of the study. But Chuck...

Yes. I think the conversations we would have naturally premarketing with payers rests on that, where is that optimal mix. Because the message you'd like to lead with is we have superiority on bleeding. There is a cost to bleeding to the system for those patients who experience bleeding. And the question then, well, what is -- what's the trade-off? So hopefully, we do not have a trade-off and say we are not sacrificing any efficacy. So if you look at that alone and even to Cristian's point about 40% of patients on Eliquis, which is a big number, who are underdosed or not dosed and the cost associated with that in terms of foregoing efficacy or causing some unintended bleeds, there's a lot of value to the system there. So as we get the data, and we'll have a more fulsome conversation in the context of the Phase III data. But we would expect the value that, that potentially that brings to the system would be reflected in access, pricing as we look to payers and to patients and prescribers.

And I guess on that point, maybe just staying with that thread, Cristian, back to you, how do you think about the commercial implications of hitting your non-inferiority margin, but with a point estimate of a hazard ratio of maybe slightly above 1?

Will be the totality of the data. I think we can't speculate. It's 1.0, 1.05, we can't speculate about it. But ultimately, the data, the totality of the data will give us the profile of the drug. The study has been designed to hit 1.0 as a ratio. It can be even better, but this is the assumption. And then on the bleeding rates, I think we should be able to see some benefit. I have to say Factor XI inhibitors, [ milvexian ], also other drug are showing consistently to be beneficial on the bleeding rate. So I believe that we are on track with that trial. Let's see. The good news is not far away. So we need not to wait too long.

Yes. All right. Let's move to neuro. Let's talk about Cobenfy. Maybe just open-ended question, give us your latest framing and update ahead of the ADEPT-2 -- 1, 2 and 4 trials.

Yes. The Cobenfy is a big area of focus that we are having. As I was telling, we are building, we have now built a good infrastructure, a good unit in Europe. I'm very pleased how we are progressing. Consider the Cobenfy, we have 12, 13 pivotal studies ongoing. So it's a very large program. So there are 4 studies in psychosis, Alzheimer's psychosis. There are 3 studies in bipolar, 2 studies in agitation, in cognition for Alzheimer's and then autism irritability.

So it's a large program. We have multiple shots on goal. Psychosis is the first potential readout for the product. The base case is having at least 2 positive studies to be able to go and try to seek for an approval. As you know, ADEPT-2 and 4 are similar even if there are differences because ADEPT-4 is a biomarker selected population. We wanted to have a more homogeneous patient population. It's based on tau plasma assessment. Of course, this increased a little bit more than a little bit the screening failures because we want patients that are positive, but it's progressing well.

And ADEPT-2 now restarted. We learned from ADEPT-2 executional hiccups that we had and now I am full confident how the program is delivered across. ADEPT-1 is a different study because it's a study in which we have not assessing like in ADEPT-2 and 4, a time-bound score that is measuring hallucination and delusions at baseline and after 14 weeks. But we are recruiting psychotic events. The patient starts with a run-in on Cobenfy and then is randomized to continue Cobenfy or placebo and then the patient experiencing psychotic events is collected as an event.

And then the analysis is based on a predefined number of events. So different studies, but they are complementary. So ADEPT-1, 2 and 4 are running in parallel. They should read out more or less at the same time, but it depends on the -- events. So there is -- we will inform why we will -- we guided before.

And which one of those additional indications that you mentioned does the ADEPT trials have the most read-through to? The additional indications that you were talking about for the Cobenfy program.

I mean, I think psychosis is very anchored on 3 factors. The first one, xanomeline show good activity in the past for hallucination -- for productive symptoms like hallucination and delusion. We have seen in schizophrenia in patients with these symptoms benefit. And when you have antipsychotic drugs that are working in one indication, you can translate that into other indications. This is why we believe that this can be beneficial also in psychotic events in psychosis in Alzheimer's. And of course, we have data from some of the open-label part of the studies where we see some activity, yet we didn't disclose.

So I think the ADEPT program is anchored on this. Bipolar that is the next coming next year, I think it is also anchored on similar symptoms because we are treating mania in these patients that are experiencing bipolar underlying disease. So I think I believe that this is also an area where Cobenfy can bring benefit. Agitation, if you think, is very linked to productive symptoms. So in my view, is also an area that can be beneficial. Cognition is different. Cognition is different because while the prior trials are anchored more on M4 inhibition, cognition is more M1 muscarinic 1 receptor inhibition. So it's a little bit different concept.

Overall, I believe that Cobenfy is a drug that in schizophrenia is bringing a lot of benefit to the patient. And it's a drug that will have on symptoms control. So this is something where I believe we wanted to invest largely with this drug because, first of all, the medical need is huge. And secondly, because the data we see and the benefit the patients are getting from schizophrenia give us confidence. Then I want to build on Cobenfy because Cobenfy is an anchor, but there is substrate below Cobenfy. We are building a very strong Alzheimer's portfolio. We have an anti-tau antibody, and we have some novel drug that can work both in MS spasticity and also in agitation that are in Phase II. Next year, we will have data with these drugs. And we will have some early development assets. So we are building a neuroscience presence.

Okay. I want to talk about admilparant. But before I do that, Chuck, you've been waiting patiently. And I just want to maybe give you the opportunity to highlight just sort of business trends, anything as we're closing the quarter that you want to touch on. David said that the company was trending towards the upper end of guidance on the first quarter call. So just high level, how are things progressing?

Yes. Business continues to do well. The growth portfolio is delivering, executing on the pipeline. Obviously, as you mentioned and spoke with Cristian, a lot of readouts coming this year. We're often asked about business development. If you take a step back, our objective following the LOEs, which are going to be in the rearview mirror before too long, we want to have not just visible growth post the LOEs, so later in the decade into the next decade, but durable growth.

So there is no hesitation on business development in terms of the question we get often, are you waiting to see all the Phase III readouts before you look to execute business development. There's no go slow order, so to speak. So we continue to look in the areas we know well where we understand the biology. We understand what the unmet need is. We understand could we get a fair return for investors. So we continue to look at that. And it doesn't need to only be acquisitions. We've got plenty of examples of partnerships, even out-licensing. So I think for us, focus on delivering on our numbers this year.

The readouts will be what the readouts are going to be. We've done a very good job managing our cost structure as we go into the LOE period, we'll be a smaller company, and we want to have the appropriate cost structure. So when we turn that corner, we have got very good leverage from top line growth, again, durable, visible top line growth being translated into even stronger bottom line growth. So execution focus are the clear mantras. And back to the end of the decade, our goal is to be one of the fastest-growing biopharma companies coming out of the decade.

Okay. That's great, Chuck. Cristian, maybe back to you in the interest of time. We just have a couple of minutes left. I have 2 topics I did want to talk about. I'm going to let you choose. I don't know, admilparant and Camzyos, which ones -- where do you want to go?

Admilparant.

Okay. Let's talk about that. What level set us?

It's -- I like the target. LPA1 is novel. And pulmonary fibrosis is a disease. There are not so many options. Having a drug that can bring a novel target, very helpful is a target that may work because we know LPA1 is attracting and inducing fibrotic process through fibroblast activity, but also induces cell death apoptosis for epithelial cells. So by blocking that target, potentially we can even increase the repair system. So I like this concept.

Secondly, this is a drug that you can deliver as monotherapy on top of antifibrotic therapy because the profile -- the safety profile is very neat. The program has been -- the Phase II -- the Phase II, the Phase II was positive in IPF and PPF. The Phase III was very, very much run to try to replicate the conditions for the Phase II. This is the secret to have most of the time a good outcome in Phase III. In addition, I think we were able to integrate a higher dose that in my view, helps because we have seen a dose relation in efficacy with -- between 30 and 60, 60 was actually the dose.

But then we took the risk to put 120 into the Phase III. The DMC assessed 120 in safety run-in and efficacy run-in and give the green light. Then the studies have been conducted, more than 1,200-patient studies, each one of them, 2 doses, 120, 60 placebo. And the good news is that we didn't have any safety signal in terms of hypotension, syncope episodes. So this is a bit longer. And of course, we will see when we unblind the data, but we have 2 shots on goal and 120 can give us more confidence that we can have also a better outcome. We will see the results. Again, we don't have to wait too long because it's happening this year.

And is this filing strategy going to be to maybe file both IPF and PPF together?

I think the other good news is that the PPF, initially, we were thinking with a little bit bigger gap. Actually, we were able to recruit the PPF very rapidly, and this allowed us to have the 2 studies a few months apart. So there are 2 separate studies, but yes, potentially the regulatory strategy can be one.

Cristian and Chuck, thank you both very much for the time. I know we went a little bit over, but there's obviously a lot to talk about. So I really appreciate your [indiscernible] soon. Thank you.

Thank you.

All right, everybody. We're going to get going here with our next company presenter at the BofA Annual Healthcare Conference. My name is Jason Gerberry. I cover pharma and biotech. And I'm pleased to be introducing our next company presenter, Bristol-Myers Squibb, and Adam Lenkowsky, Executive VP and Chief Commercial Officer.

So Adam, thanks for joining us.

Thanks for having me, Jason.

Yes. So great. Look, there's a lot to talk about. I think Bristol is at an important inflection point as a company. You're rolling through some older franchises, but you've got a lot of pipeline on the come and some products that are early in their launch process. So I think we have a lot to talk about.

Maybe coming out of 1Q and as you kind of think about the growth portfolio specifically, maybe just talk about some of the puts and takes with that versus the legacy portfolio and how things are coming along just in the base business.

Yes. So we've got very good momentum in our growth portfolio. As you saw in Q1, we delivered 12% growth year-over-year in the growth portfolio.

And as you said, it's a very young and diversified portfolio. Products like CAMZYOS and BREYANZI delivered strong growth, annualizing both at well over $1 billion. REBLOZYL is annualizing now north of $2 billion.

And then some of our newer launches, OPDIVO Qvantig, we're seeing really strong conversion rates from the IV formulation. And of course, COBENFY. COBENFY is delivering steady growth, and we've got a number of catalysts to look forward to over the next 12 to 24 months, including things like Alzheimer's disease psychosis readout, bipolar readout, Alzheimer's agitation.

So taken together, we feel very good about this portfolio, which will drive strong growth through the end of the decade.

We're also seeing continued growth for ELIQUIS, giving us really nice cash flow, with our Pfizer counterparts. We expect to see double-digit growth this year for ELIQUIS. And that's offsetting, in our legacy portfolio, products like REVLIMID and POMALYST, which has now full generic entry.

So our growth portfolio coupled with truly an unprecedented number of data readouts, we have the potential to launch 10 new medicines in 30 meaningful life cycle management indications by the end of this decade, by 2030, we feel really well positioned to be one of the fastest-growing companies exiting 2030.

Okay. Great. Let's start with CAMZYOS then. I think you've highlighted that you've got about 25,000 patients, I think, treated today, with additional diagnosis as a driver of this market. It's kind of the key toggle in the market model. So how should we think about the pace of diagnosis expansion and the ability of these centers of excellence to scale capacity from here?

Yes. So again, as I said, we're delivering really good performance with CAMZYOS, strong execution from the commercialization teams. And I think we're seeing a couple of things happening. Number one, steady growth of new patients, as well as long persistency, long durations of treatment.

Our focus is twofold for CAMZYOS. Number one, there's still, Jason, about 100,000 patients today that are diagnosed with oHCM. So that's our first business opportunity, to source as many of those patients. But this is a market that we've also created, now 4 years down the road. And so what we see, every single week, which is remarkable for a product that's 4 years on the market, is new prescribers largely in the community. And that's another proof point around growing diagnosis rates.

We also have partnered with a company called Viz.ai. It's an AI-based company that they are in about 120 of these centers of excellence. And what we've been able to see, they have now screened over 3 million Echos. And with that, they've been able to increase the diagnosis rates, and we expect that to continue. That, coupled with new competition in the market, we believe this is a really good opportunity to continue to grow the market while sourcing the diagnosed patients that are out there today.

Okay. And then with respect to new competition you mentioned there, any observations, early changes in the market, if any, that you're seeing? Or is it just too early to say how that competitive dynamic plays out in the area you have indication overlap?

Well, we've been planning for competition for quite some time. We continue to hear from physicians that there really isn't any meaningful differences between the 2 products. You're right, it's still early. But what we see is from the COEs, that they've prescribed maybe 1 or 2 patients, what we hear back from our physicians is that they're utilizing the CAMZYOS workflow, the fact that CAMZYOS has been out, it's very predictable dosing, Q4 weeks. So they're leveraging that Q4 week dosing for the competition as well.

We think this is really significant for CAMZYOS because patients -- most of the patients are on either 5 or 10 milligrams. And so patients are going to feel better almost immediately, versus what we've seen with the competition, you really need to titrate that up to the highest 2 doses. So again, it's early, but we remain steadfast that we're going to continue to lead in this market in the near term and into the future.

Okay. And then just quickly on the ACACIA results. How attractive do you see the non-obstructive HCM space now and your ability to play catch-up there? Because I know there's an expressed interest to revisit another trial there.

We announced on our earnings call that we were starting a new non-obstructive HCM Phase III study, based on the learnings from the ODYSSEY study that we had. We obviously need to see the full data results from ACACIA. But I think largely, it confirms what we saw in ODYSSEY, that numerically, with the data that has been put out there, the data looks very similar in KCCQ and pVO2.

Now in fairness, they hit stat sig; we did not. But I think there are a lot of learnings that we were able to apply from ODYSSEY. We'll need to see their data set. But this is 30% of the market, and we want to make sure that we're competing in the entirety of the market, not just the 70%. But our focus really is trying to source those 100,000 patients, which gives us growth way well into the foreseeable future for CAMZYOS.

Yes. Okay. Maybe shifting to Qvantig, and you've got roughly about 10% conversion. And I think if you continue on this pace, you'd be at that 30% to 40% target at the time frame that you've talked about. So what my question is, is just the key factors that could determine whether there's an acceleration to that conversion profile?

Yes. The team is also -- they're executing really well with Qvantig. As you said, we're now north of 10% conversion rates. We're tracking against our objective, which is that 30% to 40% peak conversion share over the next 2 years. We're seeing use for Qvantig across a multitude of tumor types, seeing it in monotherapy, in our adjuvant settings, but also in combination such as in RCC, GI, melanoma.

Here's what we would expect. I would expect a very similar pace of uptake over the next year or so. And then we get the results of CheckMate 1533. CheckMate 1533 is a study that's looking at the 9LA regimen, which is our metastatic first-line lung regimen, using the subcu formulation. You may recall, that's not in our label today. And that represents about 20% of the total IV business that we're unable to tap into right now. We'll get those results. They will likely be added into NCCN guidelines, into the label sometime in 2028. And that will serve I think as that next catalyst of growth for the product. So I do see an opportunity to further accelerate the Qvantig performance.

In lung?

In lung, and continuing the pace across the rest of our indications.

I guess, how are you thinking about the plenary at ASCO with the bispec and the potential impact of a shift away to maybe a PD-1 monotherapy backbone and how that impacts these subcuts in the lung setting?

Yes. So first, let me just say, we are really excited about the ASCO coming up. We've got some important data on pumitamig in lung cancer. We've got really exciting and promising data for iza-bren in breast cancer, which is the product that we are partnering with SystImmune. And then, of course, the results of our Phase III study with mezigdomide, which is our second CELMoD that will come to market.

I think the timing really lines up perfectly, because by the time that biosimilars start to come to market, we'll start to see data readouts for pumitamig in the '28, '29 time frame. And so the vision really is to be able to get the product to market, in lung, in breast, in gastric and a host of other tumors. As you know, we've got 7 Phase III studies that we're actively recruiting for today. And that gives us the opportunity to not just maintain, but to grow our IO franchise into the future.

Okay. Maybe just come back to oncology, but the treatment of these subcut combinations, IRA, are you expecting anything this year, visibility in whether or not the subcuts rolled into the treatment of IV PD-1?

Well, what you saw is for IV that the MFP effectuation was pushed 1 year into 2029. We have not received any new information around subcu. We had expected that last year. That was deferred. We're continuing to monitor that. We are strongly opposed to having subcu included into the IRA negotiations in the same time of IV.

This is a very novel mechanism that's very different. We're using the Halozyme technology, as you know. And so we've been working with policymakers to reinforce how this technology is truly differentiated from the IV.

Yes. Well, let's shift to the pipeline because that's a huge area of focus for investors, and milvexian. You have a lot of know-how in this space given ELIQUIS. And so one argument that you may hear from physicians was, hey, warfarin was just a rough drug to use, had a lot of burden on the system, right, so that was maybe an easier drug for ELIQUIS to displace. As we think about scenarios, are there scenarios where milvexian data-wise could replace ELIQUIS in full?

Well, clearly, that's our belief. Our belief is that the study was designed to show a superiority benefit in bleeding, and we know that bleeding is the most significant unmet need out there, even with products like ELIQUIS, and a comparable efficacy profile. This is a meaningful opportunity for patients, particularly payers where there would be a clinical and a pharmaco-economic benefit, and prescribers, because prescribers tell us they want a drug that they can be confident that they can use across a very broad patient population with minimal bleeding. We talk a lot about, and you've heard us, Jason, talk about that 40% of patients who are either untreated, under-treated or discontinued treatment.

I would also say that if you and I were sitting here about 10 years ago, you would have asked me the question, "Well, why is there so much stickiness in warfarin?" Because at that time, a few years post the launch of ELIQUIS, warfarin still had a 30% or 40% market share. We were talking about Coumadin clinics and it takes time. We're getting fast-forward now over 14 years, and ELIQUIS is not just the leading NOAC, but also has about a 75% share.

So it's going to take -- continue to take time, but we feel very confident about the profile that milvexian will bring to patients, payers and prescribers, and the fact that this could become a true standard of care.

Okay. So when I think about data that you may be able to get and market for around milvexian, if you're able to show a neutral impact on stroke, right, that's table stakes. And then it seems like perhaps the sliding scale is the degree of superiority that you show on bleeding. And that absolute delta is bigger, and thus, like the NNT is competitive, the number needed to treat, am I thinking about the right toggles that may scale the size of this commercial opportunity beyond just, I guess, the lower-hanging fruit, which is those who can't take ELIQUIS because of bleeding risk or suboptimally dose, which I think you defined as 40% of the api or is that 40% of ELIQUIS population?

No, it's 40% roughly of the 10 million patients in the U.S. that are diagnosed every year. The way we think about it is how you actually think of it, that's our base case, which is delivering a stat sig improvement in bleeding. And that could be significant in terms of the percent that we believe that milvexian can show a bleeding improvement over that of ELIQUIS.

We know very -- we're very familiar in literally millions of patients through real-world data what the bleeding profile is. We've seen that data also in study, in clinical trials, in real-world data. And so we do believe that this is going to be a significant benefit in bleeds over standard of care ELIQUIS.

The question then becomes, what is the efficacy difference in events, in stroke? And I think that's really -- what we are anticipating is to see a comparable effect to ELIQUIS. And with that profile, we think that's the very significant opportunity that we believe we have in the market.

If that didn't manifest, for example, if you saw a slightly higher hazard ratio in efficacy, then we would need to look at populations that have, for example, higher risk of bleeds, such as the elderly patients, frail patients, patients with renal disorder, PAD and/or CAD, which is still a very significant population. But as I said, that's not our base case. Our base case is a hazard ratio that is close to 1 and a stat sig efficacy profile.

So I think what you're describing though, just so I'm understanding correctly, like the point estimate is 1.2, and doctors are starting to kind of say to themselves, "Hey, what are my trade-offs on stroke?" But it's still approvable because it falls within the technical criteria on non-inferiority. Then docs look to the subgroups, and commercially, then, they may skew utilization to some of these higher-risk subgroups, depending on how the forest plot looks.

That's right. And I think, look, we're not expecting a 1.2 hazard ratio.

It's hypothetical, but, yes.

So I don't think it probably makes sense to hypothesize, but certainly, as I said, if that was the case, we'd have to look at subpopulations looking within the study. But our base case and how we've continued to model ELIQUIS versus milvexian in a blinded fashion gives us a lot of confidence that the profile will read the way that we've articulated, which is comparable efficacy and superior bleed profile.

Yes. I mean one question that's come up in some of our recent doctor calls is that perhaps the annualized bleed rate of ELIQUIS has come down versus, say, 2010 when the pivotal trials were run then, versus, say, OCEANIC-OF (sic) [ OCEANIC-AF ], what the annualized bleed rate is. And so you have a massive trial, right, so presumably, it's powered to show some degree of superiority. But if that superiority is small, right, and it's a very large NNT, do you think that that matters commercially?

Doctors have not talked about number needed to treat as a factor in uptake. I really think if you have a stat sig benefit, it's going to be incredibly compelling, particularly to payers where they know that bleeds are a leading cost for payers, they're a leading cost for employers. I also believe that a product like milvexian is going to show significant pharmaco-economic benefits.

And we talk a lot about major bleeds, but these -- NOACs also come with nonmajor bleeds as well, which are challenging for patients, as you can imagine. So that's why you do see such a significant need out there, because patients are discontinuing their treatment prematurely when they see a nonmajor bleed. And that's the -- I think the significant unmet need out there is a product that has the same, if not slightly better, efficacy than ELIQUIS, with a superior bleeding profile.

Yes. Okay. And then a quick question on SSP. I don't see why you'd have a different outcome than Bayer. I think Christian has said that the baseline demographics of your study are very similar to the OCEANIC SSP trial. So that's all encouraging. So your just thoughts around this opportunity now as you've gotten to see the data and better understand what that could mean from a commercial opportunity. I think in the past, I think 8 to 10x larger than SSP. Does that ratio still hold in your mind? And anything else you want to add just on the SSP opportunity?

Well, number one, I think there's a clear advantage to having both indications, becoming the stroke prevention drug, having secondary stroke prevention and AFib as an indication. As I said, there are about 10 million diagnosed patients in the U.S. So this is a much larger opportunity than that of secondary stroke prevention.

That said, when I think about what we've seen from our own Phase II data, a large Phase II study, looks very similar to the Bayer study. We had roughly a 30% relative risk reduction in events, very low bleeding. So we would expect to see a comparable profile to what Bayer has shown just based on our own data. It gives us obviously increased confidence in the data set, as Bayer has presented their Phase III. But we feel good about both opportunities that we have in front of us.

And the good news is we don't have to wait that long. We'll see data by the end of the year and you'll see what the results bring.

Yes. Okay. Maybe we'll move to admilparant in IPF. Pulmonary is not a huge area of focus for Bristol currently, but I think there are a lot of clear commercial success stories in the IPF and there's a lot of clinical attrition stories as well on the development side. So I guess the one encouraging thing is that BI had an oral follow-on, and it's been around for about 5 months, started already annualizing at $1.5 billion. I don't know if you view that as, "Wow, this is like they're going to have a first mover advantage on us, that's going to be hard to displace them." Or do you just look at that as like this market was truly under-treated because people couldn't tolerate antifibrotics and there's just a lot of opportunity out there?

Yes. This is an exciting and, I think, an opportunity that's probably underestimated externally, but it's one where we've got a lot of enthusiasm about based on the Phase II data that we've seen. Another Phase III study in IPF we'll see the results this year, and then PPF early next year.

But I think what we have seen now with the launch of Jascayd just confirms what you were alluding to and what we know, is that this is a market that even if you have modest efficacy and tolerability improvement versus standard of care, which is what BI has shown, there really is a significant commercial opportunity. It's a $4 billion market today. We think this market can more than double at peak.

And what is happening and what our thought leaders have said is that with the profile of admilparant, the first LPA1 antagonist into the market that will offer really robust efficacy with minimal GI toxicity, has the opportunity not just to be foundational and first line, but what you're seeing today happen now with the new entrant and what we expect to see with the versatility that admilparant offers, the opportunity to be an add-on and/or a switch. That market didn't exist, which is another reason why we expect to see significant growth.

So we feel really good about where we are with both our IPF and PPF program. You are right, this is a new area so there's a lot of work that needs to get done from now until approval. But we know the work that we need to do to get this product to market, and we expect this to be a significant player in IPF and PPF.

Okay. Maybe to CELMoDs quickly. The space is incredibly fluid, increasingly complex, that being the multiple myeloma space with recent data from Tecvayli, I think there's open questions around how bispecs and CAR-Ts will be sequenced. Maybe it's a little bit difficult to have a full view until some of the readouts like SUCCESSOR-2 come out, right, and you have a better sense head-to-head how agents like pom, or I should say, mezi compare to pom more directly. But paint the picture. Because I do hear the feedback that these drugs would generally probably resonate well with community oncologists because of the ease-of-use profile.

Yes. So we're very much looking forward to our PDUFA date for iberdomide, which is August 17 of this year based on the MRD endpoint. And then as I mentioned earlier, we will present the results of mezigdomide, our Phase III study, at ASCO, which again you'll see kind of how -- what a significant opportunity mezi and iber are, particularly in the community. I mean that's where 70% to 80% of patients are treated. That's where we believe that initially, we will have a stronghold.

And there is an unmet need in the market for a product that has increased potency versus Rev and pom, manageable toxicity, an oral drug. All those fit really nicely within the workflow of the community oncologists versus what you see with potentially combinations of TCEs. And it's why CAR-Ts can't be used outside of these centers of excellence.

So when I think about the opportunities that we have at hand, number one, we know that when you look at MRD for CELMoDs, they are significantly better than what we see for IMiDs. These products sound like they were engineered to be more potent than Rev and pom, and we're confident in that.

We'll also have 2 studies that will demonstrate head-to-head. One is going to be in an earlier line of treatment. So we have a head-to-head iber versus Rev study in first line, newly diagnosed patients. And then we'll have SUCCESSOR-1 readout, where you'll be able to see how mezi combination compares to that with the pomalidomide combination.

But taken together, this is a market we know well. We're very excited to bring these products to patients and to prescribers. And our goal is, over time, to be able to replace Rev and pom in the second-line setting.

Okay. So maybe shifting gears to just oncology and the BD strategy. As we think about the initial wave of trials to replace your PDX or OPDIVO, the coming wave of trials are going to be built on novel-novel combinations, right? So iza-bren's one logical partner there. But thinking about other kind of novel agents, does that imply that Bristol is going to be active on the BD front here to effectuate the strategy?

Yes. So I think we feel very good about our rich and deep oncology pipeline. This is an area that we've been leaders for quite some time. And we talked about some of the really exciting data that's coming at ASCO.

As far as novel-novel, we do believe that's going to be the case, that novel-novel combinations are going to replace what's largely used today is chemo combinations. So yes, we've built very deliberately our pipeline to include certain platforms. So we think we have a truly differentiated ADC with iza-bren, the first HER3 EGFR ADC.

Remember, we also have, through our RayzeBio acquisition, a platform in radiopharmaceuticals. We are leaders today in cell therapy. We continue to add to that important modality. We have targeted therapies, which we haven't talked much about, like PRMT5, which is in around 10% to 15% of all tumor types. These are in MTAP deletions. Many of these are going to be used in combinations as novel-novel. And we have a host of other products in our pipeline that we're working to rapidly bring forward.

But I think oncology is a really important space for business development because the science continues to move probably the fastest in this space. Just yesterday, we announced I think a pretty interesting and innovative approach with Hengrui, which is a Chinese biopharmaceutical company, for kind of a landmark deal with 13 assets, 4 of which we get access to that are all oncology focused. And these are potentially first-in-class, best-in-class, or TCEs, trispecifics, things that we know are going to be really important for kind of future forward combinations.

And we feel good about how we're positioning ourselves with oncology and to remain leaders in this space in the future. Pumitamig, of course, being the anchor asset there because there's so much room for continued growth in immuno-oncology. This is an area that we know so well, we go back almost 2 decades there.

Okay. So about 3 minutes left, so maybe we'll just jump to COBENFY. And as we think about sort of the early launch dynamics in schizophrenia and the entrenchment of the D2s, I guess what I wonder is, is there a market analog you can point to that, hey, with time and resources, there can be a later inflection point in the rollout in schizophrenia specifically?

So COBENFY is delivering steady growth. You saw that in Q1. And what we have seen and expect for COBENFY is to continue to deliver that similar cadence of growth in schizophrenia. And the inflections, what we have seen through analogs, come from new indications. And right now, we are ahead of all recently launched D2s in schizophrenia. There remains a very attractive opportunity to grow our schizophrenia business into the future.

But it's those data readouts that are coming in bipolar, in ADP, in Alzheimer's disease, cognition, agitation, autism, that is going to accelerate the pace of growth for this product. And we feel confident that this is going to continue to be a multibillion-dollar asset over time. But we need to add new indications, and we look forward to data readouts coming over the next several months.

Are there any issues that you see in terms of the dosing profile in Alzheimer's? I know it's dosed 3 times a day. Or is the view that a lot of these patients are in long-term care facility, nursing homes, and so, obviously, the patient doesn't need to remember to dose 3 times a day. That would obviously be problematic if the patient had to do that. But I'm just curious if there's anything inherent in the product profile that we're seeing in maybe the schizophrenia adoption that plays into the ADP opportunity?

I think there are some parallels that we need to make sure we take those learnings from schizophrenia, and we will apply them into future launches. Number one is ensuring that we're building confidence in how to dose those patients, how to titrate patients to get the best, the maximal benefit, and minimize the side effects, particularly the GI side effects.

When you're looking at an Alzheimer's patient population, safety becomes of utmost importance. And many of these patients, as you said, Jason, they are in nursing homes. So side effects and adverse events like movement disorders, EPS, excessive sedation, these products, every D2 carries a box warning for elderly-related patients with dementia.

We know that COBENFY doesn't have any of those challenges. Now we will have to make sure that physicians are confident in how to use the product, how to titrate the product. The TID dosing started with the Karuna development program. And so that's why we have ADEPT-5, which is a program that's designed to move TID dosing into BID dosing, because we do understand that although most of these patients are treated in a long-term care facility, TID dosing is not ideal. So we want to make sure that they do have the opportunity for BID.

And then we're going to continue to look at data generation, like we've just launched with our switch study as well as our food effect study, that helps physicians really be able to use the product in a more real-world setting, how to dose it, how to titrate it, to manage any side effects and to maximize the efficacy of the product.

So a quick question, I'll ask you to put your CFO hat on. There was commentary on the most recent earnings call just about that this pipeline-rich fourth quarter data flow won't impede the company's -- the ability to transact and do BD to augment the portfolio. So maybe just give us a little bit of flavor for appetite for BD, some of the parameters around that in terms of what the company is focused on.

Yes. So David has said this well, I mean, we are in a very good position in terms of having the capital to do the types of deals that we want to do. Now we're going to be selective in those deals, making sure that the deals fit nicely into our therapeutic areas. We believe we are the best owners, the rightful owners, we have the ability to win, that these assets are differentiated. But BD remains a top priority.

So we're focused on 2 key areas. Number one is using capital allocation for business development, continuing to add to the profile, not in this part of the decade, but continuing in the next part of the decade so that we continue to see that long-term sustainable growth. The other area we're focused on is paying out the dividend and making sure that we're continuing to return money to shareholders. And we've paid dividend, I think 93 years now, David would be better, 94 years potentially.

And I think that's the area that we're going to continue to do, is balance between smart business development, looking at opportunities that fit really well within our profile, our therapeutic area footprint, and then returning money to the shareholders.

All right. Great. We're out of time. So thank you so much for joining us.

Thanks so much.

All right.

Welcome to the Bristol-Myers Squibb First Quarter 2026 Earnings Conference Call. [Operator Instructions] 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. Go ahead.

Thank you, and good morning, everyone. We appreciate you joining our first quarter 2026 earnings call. With me this morning with prepared remarks are Chris 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. And with that, I'll hand it over to Chris.

Thanks, Chuck. Welcome, and thank you for joining our first quarter earnings call. We delivered a solid Q1 and continued 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 3 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 3 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, [indiscernible], Opdualag, Qvantig 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 mezignomide, our ibertamide filing for relapsed or refractory multiple myeloma was accepted by the FDA with breakthrough therapy designation and priority review with a PDUFA date of August 17. This is an important step for our protein degradation platform potentially enabling us to bring first [indiscernible] to market. For mozigimide, we reported positive Phase III interim data from the SUCCESSR-II 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 [indiscernible], we shared positive Phase III 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 III China study results Izobran 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 SOTC 2 in psoriatic arthritis and Opdivo for 2 new classical Hodgkin lymphoma indications. We also reported positive Phase I switch data for cobi positive Phase III data for KEMZYOS in adolescents with obstructive HCM and positive Phase II 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 derisk our long-term growth profile. Among the Phase III readouts expected late in the year, our Milvexian and atrial fibrillation and secondary stroke prevention, Cobenfy Alzheimer's psychosis at [indiscernible] 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. We 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 have 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 time lines and enhanced 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 Ferro, enabling us to design trials more efficiently and [indiscernible] cost optimizer tool. These ongoing efforts across R&D are top priorities for 2026. The organization's continued focus on financial discipline enables us to make these and other important investments. We remain on track to deliver the remainder of our $2 billion in cost savings from our strategic productivity initiative by the end of 2027. With respect to capital allocation, business development remains an important focus.

As always, we will continue to index on opportunities where we add strategic value and where we can deliver attractive returns. As our post-LOE growth profile becomes clearer, we'll naturally place greater emphasis on expanding our early and mid-stage portfolio to support growth into the 2030s. In summary, based on our performance, we see the business currently tracking towards the upper end of our guidance ranges. Looking forward, we have continued momentum in our growth portfolio, broad potential in our pipeline and the ability to invest in our business while becoming more focused and efficient in how we operate.

With that, I'll turn it over to David.

Thank you, Chris, and good morning, everyone. Our performance in 2026 is off to a strong start as highlighted by our first quarter results. We delivered solid R&D, commercial and financial performance while continuing to manage our cost structure. Our persistent focus on execution has further strengthened our foundation as we position the company for long-term sustainable growth. I will begin with a review of our first quarter results and then discuss our financial outlook for the remainder of the year. .

Starting with Slide 8. Total revenue in the first quarter was up 1% year-over-year at approximately $11.5 billion. Our growth portfolio continued to perform well with global revenue increasing 9% to $6.2 billion. As Chris mentioned, several products that are still early in their life cycles are driving growth as we intentionally expand our business across a wider range of key assets. Within the legacy portfolio, we saw solid growth from 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 U.S. This is 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 Cobenfy, 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 a 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 first quarter growth of 53% reflects its best-in-class profile and continued strong demand across its approved indications in both the U.S. and international markets. We remain encouraged by 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 U.S. price reduction that took effect at the beginning of the year, we also saw some wholesale 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%. And recent approval in cirrhotic arthritis represents a continued presence in rheumatology while we await our Phase III readouts in lupus and Sjogren'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 Pumitamig, [indiscernible] 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 $0.03 a share related to in-process R&D and licensing income.

Turning to the balance sheet and capital allocation highlights on Slide 14. Our financial position remains strong with approximately $11 billion in cash equivalents and marketable securities as of March 31. In the first quarter, we generated approximately $1.1 billion in operating cash flow. This quarter's cash flow reflects roughly $1.2 billion and 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 from us. We will continue to provide updates as the year progresses. In closing, our strong performance in the quarter reinforces our confidence in our ability to deliver long-term value for our patients and shareholders. And to reiterate Chris' comment, our strategy remains grounded in 3 priorities: focusing R&D on life-threatening diseases, driving strong execution across the organization to build momentum in our growth portfolio and maintaining disciplined shareholder-friendly capital allocation.

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

[Operator Instructions]

The first question today comes from Asad Haider with Goldman Sachs.

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

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

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. And let me start with what we already achieved because in NIM, I think we had a positive MRD with Iberdomide in caliber in and we are expecting the PFS later this year. As Chris mentioned in his opening remarks, the PDUFA date for this filing is August [indiscernible]. We got breakthrough designation, priority review. So it's progressing at pace. We achieved the mezigdomide this year with access to oral presentation at ASCO, really looking forward to show you guys the data.

In NIM, we will have a readout also with our [indiscernible] that is a GPRC5D CAR-T that is happening later this year. Moving cardiovascular milvexian, as you was mentioning, are importantly doubt, both AFib and SSP are continue to be expected by the end of the year. We have -- we are recruiting the events is an event driven. And of course, we remain blinded, we are recruiting the events as planned. And we at BMS are regularly is reviewing the data and even in the most recent meeting, they recommend to continue the studies as planned.

So BMS will be the only 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 remains absolutely unchanged for milvexian in this space.

In neuroscience, we continue to expect the ADP studies, a den, 2 and 4 by readouts by the end of the year. This is based on very -- we are managing the studies and moving the studies more or less at the same -- with the same time lines. So they are lining up quite nicely. We need the 2 studies probably for an approval. This is the best case, but for refining, but we will see how the evolution in this space is happening. The confidence that remain unchanged also for Cobenfy study designs, trial conduction is now completely under control. And of course, the reason to believe in Cobenfy the space are very clear. Prior data the data that we are seeing in schizophrenia and of course, the open label in Adept 1 were patients before being randomized to receive Cobenfy 12 weeks give us confidence in potentially bringing this drug in patients with [indiscernible] disease in psychosis.

Last but not least, to me, critical readout this year is Admilparant in immunology, in IPF and PPF. This is a novel mechanism -- this is an inhibitor that can bring a novel mechanism to patients with is very, very difficult to treat disease, is a first-in-class asset with a very differentiated profile, not only on efficacy side but also on the safety side. IPPF is guided by the end of the year. PPF will be just a few months later, probably beginning '27, Very solid Phase II data. I'm very pleased on the execution of the Phase III programs. So this is another important therapeutic option. As Chris mentioned, there is much more this year, next year, I have to say, it's an exciting time to be at BMS.

Thanks, Cristian. And then just on your BD question. Look, BD continues to be a top capital allocation priority for us. It's not impacted by the end-of-year readouts. We have a very strong late-stage pipeline. We certainly don't need to chase deals. But as we've said consistently, if there are opportunities that make sense for us to enhance near-term growth, we have the financial flexibility to be in the mix.

At the same time, we're building for the long term, and we're going to continue to add to our early and mid-stage pipeline as well. And of course, given the size of those deals, we can certainly do both. Irrespective of phase of development, though, the opportunities we're looking for are 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.

The next question comes from Jeff Meacham with Citi. .

Great Morning, everyone. Thanks for the question. Cristian, on Pumitamig, I wanted to check on the cadence of data in, say, the next 6 to 12 months? And would you wait for more mature data on PSS before you really expand the number of trials? Or are you ready to go right now? And then real quick for Adam, just to talk through the Qvantig dynamics versus Opdivo and where you're seeing the biggest demand? .

Thanks, Jeff. Cristian and Adam.

Jeff, for the question on Comite. Let me start with ASCO. ASCO will be an important meeting this year for PD-1 BGF 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 II data in [indiscernible] cell lung cancer in front line as a global data set after the China data we presented previously in other indication in a few days, the abstract will be released.

Our strategy with Pumitamig is replace and expand. We want to replace PD-1, PD1 inhibitors, and we want to expand beyond them. We announced and we deliver it studies across indications. All of them are ongoing and all of them are recruiting actively. What is very important, in my view, is also what we are doing beyond the first wave of trials. The confidence in my view, is becoming more and more tangible in terms of level of activity, a combine ability that you have with PD-1, PD-L1, GF inhibitors by specifics. And in my view, this is potentially translatable across indications.

Now the next step at reading our strategy is novel novel combinations. And BMS has a very rich oncology portfolio, Biotech has also an important portfolio of oncology assets. And what we are doing we are combining now -- we started the combination of Pumitamig with these other drugs that represent an enabler for other regimens, also using some combination with the standard partners. On our internal side, we started the combination with our Iza-bren ADC, which is an EGFR [indiscernible]. You will see that as Chris was mentioning at ASCO, In esophageal real negative is a very active ADC.

And I think we mitigant represent a very powerful regimen. We start the combination with our [indiscernible] inhibitor, our meta very do tight drug. So in summary, I have to say that the partnership with biotech 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 cancer patients across indications.

Yes. Jeff, thanks for the question. As it relates to Cobenfy, we're pleased with the Cobenfy launch performance. Our teams are executing well. And we're seeing use across multiple tumor types. We're seeing uptake in our monotherapy indications as well as in combination treatment. So in RCC, in gastric cancer and in melanoma. We're continuing to hear positive feedback from community oncologists that Qvantig improves practice efficiency with a 3-minute in-auto injection and that patients prefer gigantic when offered the opportunity versus the IV formulation.

So we've now delivered over 10% conversion from IV to Qvantig in the U.S. in just over a year in the market, and we're tracking well against our expectations, and we remain confident in our expectations that physicians will convert approximately 30% to 40% of IV business in the next 2 years.

The next question comes from Alexandria Hammond with Wolfe Research.

On [indiscernible], given the size and breadth of the [indiscernible] program, seems like there's probably a rich set of outcomes between the clean wind and mix. Can you help us think through how you'd approach a subgroup analysis, particularly for patients where the risk for or calculate 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 the this patient population still supports a meaningful commercial opportunity?

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

I mean Alex, let me start with that to tell that we continue to be on track by the end of the year with both AFib and SSP. These trials are remain driven. We remain blinded. As said, the DMC continues the oversight to [indiscernible]. We are at a point in which we give us confidence that we are progressing on the right way with both efficacy and safety. Everything is continued as planned. In AFib, the study will test noninferiority versus apixaban, and then we will have a 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? .

Yes. Alex, as it relates to commercial opportunity, to vaccine represents a significant opportunity commercially. There is a need for a medicine with low bleeding risk, both in a Ib and in SSP, and we think there's a significant advantage to having both indications, we would expect gone adoption. As we talked about premium Europe-leading continues to be the main reason why physicians hold back from utilizing Factor Xa in more patients. And despite the highly effective drug like Eliquis roughly 40% of patients who should be anticoagulated are either untreated underdosed or the discontinued treatment. And that's driven largely by concerns around bleeding risk.

So this leaves a meaningful unmet need across a substantial number of patients. As a reminder, this study AFib was designed to demonstrate a superior bleeding profile compared to Eliquis with comparable efficacy. So we believe this profile is going to drive significant demand and it will be important for both patients and providers. And as Christian said, we're looking forward to the data readout at the end of this year, and we think this has true blockbuster potential.

The next question comes from Chris Schott with JPMorgan. .

Just 2 for me. Maybe first, can you just talk about Camzyos potential post your competitor approval? Just what are you seeing in the market and just how you're thinking about that evolving? And the second 1 for me was coming back to the CELMoDs that we kind of some of this initial clinical data has read out. Can you just elaborate a little bit more the role in the market you see for those products based on these initial data sets and how much of your excitement here is based more on the future readouts versus what we're seeing initially here?

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

Yes. Thanks, Chris. So Canada 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 fight the significant and rapid improvement in symptoms, and we're seeing very low drop up rates. In fact, we are approaching 25,000 patients now prescribed Camzyos in the U.S. with thousands more prescribed internationally.

As far as what we're seeing in the field, we've been planning for competition for some time. ACP has continued to reinforce that they see little differentiation. It's still early. Some physicians have started 1 or 2 patients on the competition, and they are still operationalizing their own REMS program. But we also hear consistently that the Camzyos REMS process is very clear and the infrastructure and workflow that have been established now for 4 years are very clear. and thus, PLs have shared, they'll use the Camzyos dosing and echo regimen at 4 weeks.

So we think it's a positive. And we lived that because roughly 90% of patients on Camzyos are on the 5-milligram starting dose. And it's simply 1 dose titration to 10 milligrams. So it's 5 or 10 representing [ 9% ] 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. And so our teams were well prepared for the launch of [ apacamten ], and we remain confident that we'll be the leader in the space longer term.

So as it relates to iberdomide, I think we're really excited about the launch of iber. I know that Chris and Christian have talked about this. And so I think there are a few areas that is going to. Number one, with Iberdomide, this is an area that we know very, very well in the multiple myeloma. We see that for multiple myeloma, it's 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 some regimens that can find a better experience for their patients. And we're confident that Iberdomide will provide a balance of high potency manageable toxicity combined ability with daratumumab with the convenience of an oral treatment to amplify the efficacy of IMiD-based regimen. So our goal is to make both iber and mezi foundational in multi 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.

So we know the work that we need to do to establish both iber and mezi in the market, and we're very sad to bring both of these important medicines to patients because we believe this is a real attractive commercial opportunity.

And Adam allow me to step in. Chris, I want to use the opportunity you mentioned in the question on Camzyos because I received received often the question about the nonobstructive HCM plants. I think, first of all, let me start that the level of benefit expected in nonobstructive is different than an obstructive because of the terogenity of patients and diseases is much higher. That said, we have learned a lot from [indiscernible]. We know that we are the patients and which we diseases that are affected by that can benefit most from is inhibitor like Camzyos. So I want to announce that we are planning now to run a new more focused study in non-obstructive HCM. And then, of course, the detail of it will be highlighted in clinical [indiscernible] progressing.

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

And another 1 for Christian. So you really inherited design in kind of the Milvexian trials. Can you walk me through the aspects of the trial design, patient selection that increased your confidence in a potentially successful readout later this year? .

Cristian?

Thank you, Evan, for the question. In -- I think your question is referring to [indiscernible] specifically, imagine because [indiscernible]. So in AFib, let me tell you that, first of all, the data are solidly based on a Phase II studies that we run in total new replacement. That is a very good surrogate for [indiscernible] drug. So we learned a lot from Eliquis in that space, and we know the productivity value of that kind of population for antithrobotic agents.

I think the very elegant, the refined work that has been done with Milvexian was in selecting the dose for FI. That was -- in that why we tested multiple dose levels. And ultimately, we landed with 100 milligrams twice a day, that is a much higher dose for instance that we are using in. but it's a dose that gave us the confidence based on all the work that has been done, the modeling and the work that we were able to to bring in this -- in the Phase II part, give us confidence to have at least same level of efficacy that we expected with apixaban, preserving of course of the bleeding value.

Going specifically to your question, the design of the study is to be able to show a noninferiority apixaban in net to add comparison in a very well sized study, we recruited 20,500 patients. So very well powered for inferiority margin. We disclose these margins cost 0.8% to 1.3%. And we will then, when an inferiority will be met, to test the superiority for bleedings. We test we split alpha for measure bleeding and nonmajor clinical relevant bleedings because I want to link what Adam was telling. This is a measure of probably in the clinical setting. And being able to show that the drug provide benefit in terms of decreasing the bleedings will be very important in the marketplace.

So as said, the study is fully powered, well-designed and picked in my view, the right dose to being able to show what the study predefined criteria should meet.

The next question comes from Michael Yee with UBS.

Following up on the design of the Milvexian study. If you take a look at the recent AFib results, you can see that the stroke rates are quite historically a lot lower than they were back in the original days of Eliquis. So just thinking about whether you've taken that into consideration and to what extent you think that impacts the 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. Cristian?

Okay. Michael, for the question. I don't -- we cannot disclose baseline characteristics and which kind of events that we are recruiting by we remain blinded, of course, to the study. What I can tell you, again, is that the AFIB study, the [indiscernible] study has the right sample size and of course, has a predefined number of events. We are recruiting the events as expected. And the events predefined number is for efficacy and, of course, for safety. So we are on track by year-end. It's is event driven. We are in April. We will see later in the year if this event rate will change or not, for the moment, we are on track for a year-end readout. .

The next question comes from Akash Tewari with Jefferies.

So for your Cobenfy [indiscernible] studies, you have several trials that I know [indiscernible] requires patients to have a confirmed Alzheimer's diagnosis using to imaging and blood-based biomarkers. Can you talk about why you added that criteria for the study? And was it based on any issues you saw with the ADEPT II trial conduct? And then just on CELMoDs, can you talk about your confidence on the successor on study, which goes against POMALYST showing a clinically meaningful effect size based on the results you saw in Successor2?

Cristian?

Thank you, Akash. The Cobenfy ADPET-4 decision to go into a biomarker-selected population, was based in try to decrease teragenity in the patient population. As you know, ADEPT-2 was a study that was already ongoing in the moment we acquired Cobenfy. And we wanted to have a more predefined patient population to be recruited into an Alzheimer disease psychosis setting. This is why we took this approach of biomarker positivity. That can be done through plasma or radiologically. And I think, of course, this is increase the confidence that the right patients are treated in the tria even if increase a little bit at the -- the operational challenges because, of course, we need a predefined number of patients, biomarker positive to run. So the screening failures are a little bit higher.

This doesn't take out any confidence of the potential benefit you can see also maybe in a trial like ADEPT2, where we do not have a biomarker positive study because ultimately you treat symptoms, but give more confidence that you have Alzheimer patients. This is the main reason. We are not the only one doing this taking this approach.

Going back to your second question on [indiscernible]. I think a Successor2 was a very good news not only because it -- and as you mentioned, Successor2 is an add-on study on top KD, but because it came earlier than expected. We hit you will see the task, but you already know that when you eat an interim PFS means that you eat a bar that is higher according to the study, what the study was designed for. This is answering your question on Successor1.

We believe Mezigdomide is a very potent sermon is more potent than Iberdomide, for instance, is a drug that can be very well combined with the standard of care regimens that we will see, little bit less with anti-38. This is why Iberdomide is doing that job. But I believe that the level of efficacy we have seen and the design of the study, let us believe that this drug can be better than Revlimid and pomalidomide. So the confidence or Successor1 is high and of course, is higher bar because it's not an add-on is a replacement strategy, but I think [indiscernible] high.

Thanks, Christian. And 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 good 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, BCL-6 LDD, AR LDD and this program in this platform is quite deep. It's nice to see these data maturing as they are across each and every one of these programs. So it's exciting to see. So stay tuned for that at ASCO and beyond.

The next question comes from Louise Chen with Scotiabank.

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

Cristian and then Adam, to provide color and the commentary.

So ADP, because we believe this is a huge medical need -- and we believe a Cobenfy bring benefit based on what we have seen 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 a multiple shot on goal. This is why we have Adept II and Adept 4 that are similar studies with the difference. One is biomarker selected population, the other one d1 not. And we have a Adept 1 that is more a study that will assess how Cobenfy to avoid relapses. But we also designed Adept 5.

So we have now 4 shots on goal in this program because the best case I was mentioning before is having at least 2 positive things are changing maybe. And we believe this is an important setting. Cobenfy bring benefit to patients, we want to really have a multiple shows.

When talking -- when thinking the other indication, bipolar disorder is the next one in line because we're expecting results in 2027. We are testing Cobenfy, specifically in many on the -- in the context of bipolar disorders. And if you think this is very similar in terms of the productive symptoms that we see in AD psychosis.

And then we have AD agitation AD agitation is very related to psychosis because this is one symptom that we have seen Cobenfy already providing benefit. So the confidence is high also for this. Education is coming in 2028, like cognition, AD cognition. And cognition is probably different mechanism. Psychosis is probably mediated a muscarinic receptor 4. Cognition probably by muscling receptor 1. Cobenfy is working on both. So this is where the confidence day.

So I will say the Cobenfy, we believe that can bring benefit in controlling these kind of symptoms in Alzheimer, in the bipolar patients, and this is a noncore asset for our portfolio in our science. We are building -- we really would like you to start to see how we are building our portfolio in Alzheimer with a Phase II asset and multiple Phase I assets that show the commitment that BMS has for this disease because we want to play in this disease.

Yes. Just to add, Christian, did a good job covering much of our life cycle management program. But from a commercialization standpoint, I would say, stepping back, there are approximately 7 million patients diagnosed with Alzheimer's disease. And roughly 30% to 50% have psychosis and that's elucidation of delusions and the vast majority have cognitive impairment. So this presents a real significant unmet need where there are no approved treatments today.

And we know that antipsychotics have significant safety limitations. They have movement disorders, they carry box warnings that are specific to elderly patients with dementia. And then often treated and used inappropriately rather than treating the underlying psychiatric diseases, they -- they leave patients with cognitive impairment, falls and fractures and these are all really serious issues in long-term care facilities. We believe that Covent has potential to play a very important role in treating a number of Alzheimer's disease. Safety becomes increasingly important in an elderly population, where Cobenfy is not associated with EPS sedation doesn't carry a box warning. And in those 2 areas, ADP and Alzheimer's ease cognition, Cobenfy can be the first and only product apron those states.

Let me -- thank you, Adam. Let me go back to your second question on cell therapy. I could discuss about cell therapy strategy in hematology or in a immune disease. I want to focus on that immune disease because probably is newer. And I think it's is more -- it's important that we explain the strategy that we want to put in place on the development maybe in the commercial side. I believe that BMS has a very powerful platform in this space and with 1 aim resected immune system.

And 2 is that 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 allogenic and an in vivo platform. And I have to say, this set as a part, compare many other players in the space. If you think of these products, this can be transformative for patients without immune disease because if you can eradicate B cells, you can provide benefit to patients with a severe or moderate stage of the disease. But the vision can be to use these onetime treatment before the patients start to have the organ damage by the autoimmune diseases.

The most advanced program is [indiscernible], our autologous CAR-T. We have 2 ongoing pivotal start, 1 in lupus and 1 is [indiscernible]. We have a multiple later indication ongoing, and we see a level of activity that is unprecedented. And then we have in clinic now an allogenic CAR-T that, of course, can represent a more accessible and scalable approach because from one donor, you can manufacturing 100 cells. And so this can broaden up the access, but the real transformative thing can be in vivo.

We acquired [indiscernible] an mRNA in vivo platform where you have the patients that are producing, manufacturing the cells itself worse -- so this is really -- can be transformative because they can really broaden up and give scalability in such a broad space like immune disease. So I hope I addressed the strategic -- we want to be a player. We want to lead in this space. I think we are very well set to doing that.

The next question comes from Terence Flynn with Morgan Stanley. .

I'll keep it to one. Christian, I appreciate the details on the Milvexian AFIB trial in terms of noninferiority 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?

Maybe start and then, Adam, you can opine as you want. So Terence, again, the study is designed to show non-inferiority. Non-inferiority has margins that goes, as I was mentioned, we disclosed this margin, why I can speak about it. They go from [indiscernible] to 1.3 something. So we believe in the study and the preclinical and clinical work plan in Phase II is set to show that the noninferiority is meant to have a similar activity on efficacy versus a pixel.

It is possible that [indiscernible] can have another ratio less than 1, but it's not needed. Because clinically, very commercially the success required to be similar and having a better bleeding profile in measure bleedings and clinically meaningful bleedings. And this is where the study, I think, is extremely well set and power to show the noninferiority and then superiority on the bleeding rates.

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

The next question comes from Seamus Fernandez with Guggenheim Securities. .

Great. If I may, I 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 poised to emerge here. But obviously, the key is success in clinical programs -- so just wanted to get maybe Christian, a little bit more of your sense of what are the key risks as we evaluate Phase II to Phase III -- and how do you see the opportunity beyond that?

When we look back at the Phase II and incorporated a [indiscernible] analysis from a statistical perspective, there weren't that many patients on background therapy. So just trying to get a better understanding of how you see the risk/reward heading into the IPF results and the PPF results? And 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 dropout rate that patients experience and suffer from versus some of the emerging data sets for other combinations in this setting like the [ treprostinil ] data.

Cristian and Adam.

Seamus, the -- let me start with the target. LPA1 inhibition is important because it's working in 3 dimension in the fibrotic process in IPF and PPF, fibrosis, inflammation and also repair. So this is the duty of the target. And I think Admilparant is the first-in-class in this space for both IPS and BPS. The goal here is to improve on efficacy also to have a differentiated tolerability. You know there are drugs that the patient can use today that have some GI issues, some issues. So Admilparant is very different differentiated.

The conviction on this program is sitting on the Phase II results. in both IPF and PPS. We have more than 60% improvement versus placebo in the lung function decline with 60-milligram BID. And we tested different doses. And the dose relationship is very clear. This is another and one's very important that we put in the Phase III, they give me confidence in what we are doing. Because we running -- we are running both studies, and PPF with 2 doses, 60 and 120. The dose relationship and the benefit of having I was very clear, deeper efficacy while the dose is increasing.

BMC also for these trials are continues to motor and reviewing the conduction of the study, safety and efficacy and tell us to continue as planned. So we do not see any flag, especially on safety side in terms of hypotension, syncopal events, even in overall in the trial. So 2 shots on goal in a very well-designed power study.

The Phase II and the Phase III population are very similar. We tried and time the teams did a very good job in ensuring consistency and in trying to have as much as possible in Phase III what we did in Phase II. In your question on specific on the design of the trial, in both trials in IPF, we stratify based on prior treatment, [indiscernible] or nothing. So we can use add-on in patients that don't receive any treatment. And in PPF, there is certification based on usage or not of antifibrotic. So the studies will answer that question, and the drug can be used on top of [indiscernible] as a single agent. Very high confidence on how this program has been delivered on the target, execution and looking forward to the results.

Adam? .

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 Christian described. There remains a significant need for improved therapies that slow disease progression that are well tolerated and ultimately help patients manage their disease. As you're alluding to, GI tolerability remains a significant barrier where approximately 50% to 60% of patients on treatment today are discontinuing therapy by 12 months with current standard of care. And even what we're seeing with the newest approved products, the diarrhea rate is roughly 40%.

What we're hearing from our thought here is that a 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 on many in the marketplace. So we've got important prelaunch activities that are underway now, and we are very much looking forward to the data readout in the second half of the year.

Operator, can we please take our last question. .

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

So I have a question on -- so your competitor has signaled that VEGF PD-1 compared to an IO or PD-1, may be able to show a minimal regression in hazard ratio when you go from PFS to OS. We saw a regression when we compare it to chemo, but with IO-combo, it may not be a same situation. How are you thinking about that given that Bristol is probably the only company with 2 IO combos in the market and you have seen data for both the with LAG-3 as well as CTLA-4 count on top of PD-1. So how are you thinking about this sort of regression from PD-1 -- for PFS to OS, given in the context of VEGFs kind of an important investor debate right now?

Cristian?

Thank you, Mohit, for the question. Let me start on the way we deliver these 2 mechanisms. I truly believe bispecifics are a better way to deliver 2 different mechanisms than using 2 different antibodies because you are much more on target, you are much more selective in delivering them and potentially, you can decrease also the off-target issues like adverse events.

So there is another important learning that we have had -- we are having every day with these drugs. Our Pumitamig is a safe drug. The safety is very predictable, the combinability is very high. So we know VGF is impacting PFS. This is what also you are mentioning. And I think that we will see where the data are maturing. We see even a 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 gave me a good PFS gain and the statistical significance OS gain that will be without increasing the safety in a dramatic way is good enough. Because then I can use this as a backbone and I can improve even further paring other mechanisms that can continue to increase the PFS gain and potentially translating even in a better OS. I don't think we can be so simply -- we can simplify so much like in the past, the VEGF inhibitors did not translate in U.S. because here, we have the IO component. And we still don't know how much the DGF part of the drug is giving us the upside for the IO. And it is possible actually that this is give us an uplift also for OS. So I'm excited by this by specifics. I'm excited very much about Pumitamig and the plan that we are putting in place because I truly believe this can be the backbone for future regimens for cancer patients across indications.

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

So with that, thanks for joining us today. And as always, the team is available for follow-ups. Have a good rest of the day.

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

Well, good morning, once again, and welcome to TD Cowen's 46th Annual Healthcare Conference. We are absolutely delighted to have Bristol-Myers Squibb here again with us this year, representing the company, Adam Lenkowsky, who is Executive Vice President and Chief Commercial Officer. So Adam, thank you so much for being here.

Thanks for having me, Steve.

So let's start out with a bit of a big picture. Can you remind us of any notable pushes and pulls throughout the year in terms of both revenue and OpEx we should be considering?

Yes, happy to do that. When I take a step back, when you think about 2025 performance, we delivered strong performance and execution. And so we had good momentum coming into 2026, particularly with our growth portfolio. So products like Reblozyl, Breyanzi, Camzyos all performed well. We expect that to continue this year. We are now in year 2 for launches like Cobenfy and Opdivo Qvantig. So -- will also contribute to the growth of the company. That said, there are also some headwinds. As you know, we have now full generics in the market for both Revlimid and Pomalyst as part of our legacy portfolio.

And I should say, and I talked about on the call, although not part of our growth portfolio, that will be offset by significant growth of Eliquis this year, we expect to see double-digit growth. There are some notable quarterly dynamics that David touched on, on the call. I think we saw a significant inventory build in Q4, particularly in our U.S. oncology business. So our [ IO ] franchise, Opdivo, Yervoy, Opdualag and to a lesser extent, Reblozyl. And so we're seeing that happen now in the first quarter. We're seeing that inventory burn that should normalize by the end of the quarter, and we don't expect any significant deviations for the year.

As far as operating expense, we've been very disciplined in our overall operating expense. Recall last year, we did have higher OpEx in the second half versus the first half. That was largely due to some of the deals that we made, our partnership with BioNTech as well as the acquisition of Orbital had increased the percent of R&D spend in the second half of the year. We expect that to normalize this year. So taken together, and I think about the performance of the growth portfolio, the financial discipline, I know we'll talk about the unprecedented number of Phase III readouts that we'll have this year. We feel like we're in a really good position to execute on our strategy of driving long-term sustainable growth.

Great. So let's dig into some of those commercialized products first, and then we'll go more to the products that are on the way. Let's start with Camzyos. So how is Camzyos performing versus what the plan was? And you have new competition. So how can you beat the competition?

Steve, Camzyos continues to perform very well. As you know, it annualized last year at north of $1 billion. We saw consistent and sustained increases in new patients. These are patients who will be on treatment for many, many years, and we continue to see that happening this quarter as well. Secondly, what we're seeing is we're -- even though we're 4 years out almost from the launch, every single week, we're continuing to add new prescribers into Camzyos treatment. And that's happening at the community practices as well as some of the smaller institutions. It's a very positive sign as we're looking to broaden the business outside of the COEs and the roughly 500 centers of excellence.

Now as it relates to the competition, we've been expecting competition in this space for quite some time. What we had heard from physicians for over a year that they did not believe there is any meaningful differences between Camzyos and Aficamten. I think when you see the label and the approval that they've had now coming to market in January, that continues to be reaffirmed by our customer base. They don't see any meaningful differences. And we remain steadfast that we're going to be the leader in this space for the foreseeable future.

By the way, if you have a question and you're in the audience, just raise your hand, and we'll do our best to get the question answered. Let's go to another approved product that being Opdivo subcu. So are you on track to achieve the 30% to 40% conversion of Opdivo with the subcu by 2028? And what obstacles, if any, are the payers putting in the way of adoption of that...

Yes. So we feel good about the performance of Opdivo Qvantig in its first full year on the market. Remember, what we talked about last year was receiving our permanent J-code on July 1, and we saw a nice inflection of sales performance in the back end of the year, largely due to continue to build confidence in reimbursement with the community. What we're seeing with Opdivo Qvantig is use across a broad number of tumor types in the community. So we're seeing use in monotherapy. We're seeing use in combinations, whether it's in GI, RCC, metastatic melanoma.

And we hear consistently from our community oncology base that Opdivo Qvantig improves practice efficiency, improves the economics of the practice -- and then finally, from a patient standpoint, it's really patient-friendly. When they're offered an opportunity to go on the IV or on the subcu, a 3-minute in-office subcutaneous injection is clearly preferable. So we are on track to deliver against our roughly 30% to 40% conversion commitment, and we're really pleased with what we're seeing from this launch.

Okay. Similar question this time about Cobenfy. So how is it tracking against plan? And what is the outlook?

Yes. Cobenfy in its first full year on the market, we made good progress. What we're seeing in a highly entrenched market is increasing the number of prescribers each week. We are focused on driving both depth and breadth of adoption. And what's a positive sign of those physicians who have a positive experience with Cobenfy, they have an increased proclivity to increase their depth of prescribing. This year is an important year as we look to bring new data sets into the market. In fact, by the end of this month at a conference called SIRS, which is the Schizophrenia International Research Society, we will have our Switch study, which is a Phase IV study that was conducted. And that is the #1 question that we get from psychiatrists.

How do I switch my patients that will not help decompensate those patients for positive symptoms and also minimize adverse events. So we'll be sharing those data at the end of this month. and we'll be able to disseminate that data broadly across the psychiatry community. We've also increased our focus in peer-to-peer. We'll have real-world data. And so we feel good about the progress that we're making. And again, it's an important year 2, but we still expect to see steady and consistent growth from this important asset.

Great. So let's stick to the switching study for a second. How long do you think it will take physicians to embrace that data in the clinic?

Look, this is one where it's going to take time. We'll have the data presented at the end of the month. We'll publish the data midyear. We will work with our teams to disseminate the data very broadly. Unlike what you see though in areas like cardiovascular or in oncology where you have NCCN guidelines, [ APA ] guidelines have not been updated since 2020. So we wouldn't expect the guidelines to be updated. So it's going to take some time, but we're going to work tirelessly to get this in front of as many physicians as we can so they can treat patients and have the best possible experience and be able to start with and stay on Cobenfy long term.

So you've done a great job securing coverage, commercial coverage, government payer coverage for this asset and Q1 '26 should be the time where that's in full play. Is this the quarter where we can get the best picture of the potential of this drug?

We were really pleased with our ability to achieve access, particularly Medicare and Medicaid access very early on in the launch within the first 3 to 4 months. And so as we said, when you look at this drug, I mean, you could see a nice steady increase in TRxs. We'd expect that to continue. The way that we've described it is steady and consistent growth in schizophrenia. So we would not expect an inflection. We have not seen that inflection in other products.

The inflection though comes where you add new indications to Cobenfy. We'll have data readouts in the back end of this year in Alzheimer's disease psychosis. That will be a great opportunity to inflect the drug. It's a meaningful commercial opportunity. We'll have bipolar studies reading out early next year. So really, it's going to be these next indications that will inflect the product. But all of the leading indicators that we're seeing really point to a direction of this is going to be a big drug in schizophrenia and a multibillion-dollar drug longer term with a suite of new indications.

Are there any updates on the Alzheimer's psychosis trial, ADEPT -2? So are we still -- is it on track to read out at the end of this year? And how has it gone with the addition of the new patients and so?

Yes. So we are tracking towards the end of the year. Reminder, we have not just 1 study, but we have 3 studies in Alzheimer's disease psychosis that will read out at the end of the year. So ADEPT -2, ADEPT-1 and ADEPT-4 should all read out by the end of the year. We also have ADEPT-5, which is a study that is looking at a BID formulation for Cobenfy in Alzheimer's disease psychosis. So we look forward to those data readouts. We've got multiple shots on goal. And we know this product works just based on what we've seen from the open-label Phase I study. That said, we know in neuroscience studies, it does tend to be high placebo rates as well. And that's why we have multiple studies that are ongoing. But we have confidence in the study and these programs that they should hit this year.

And I understand why you're saying end of year, but that leaves open a lot of days and months. So can you be more specific as to when we might get this data?

Probably by the end of the year, you should see the studies readout.

Yes, we're talking December.

I don't know if it's December or November, but roughly towards the end of the year.

Okay. Okay. Good enough.

We'll let you know. I'm pretty sure you'll know as soon as we do.

Okay. Let's move to milvexian, another very exciting drug. What is the base case assumption within Bristol as to whether this becomes the new standard of care for Eliquis and replaces it entirely? Or do you more just go into treatment settings where Eliquis does not play?

Yes. Similarly, the good news is that we don't have to wait very long. We'll have both the data readouts in SSP and in AFib by the end of this year, reading out with our partner, J&J. As far as AFib, now this is obviously a very significant opportunity. It's an area where Eliquis dominates in the space. And so our thesis is that Eliquis is going to play across a broad patient -- milvaxian is going to play across a broad patient population, not just those 40% of patients who are untreated or undertreated based on bleeding.

But if we achieve what we hope to achieve, which is comparable efficacy with a better bleeding profile, we think this could become a potentially new standard of care in treating atrial fibrillation. We know that bleeding is the #1 reason why physicians tend to either underdose or they don't dose. It's also the #1 reason why Eliquis dominates in the space over Xarelto is why it's because of the literally millions of real-world data patients that we have in looking at improvement in bleeding profile. So we're excited to see these data read out, and we believe that this could be a new standard of care in atrial fibrillation and really become the stroke drug if we have approvals for both SSP and for AFib.

Great. I should tell the audience, we do have a cardiovascular panel this afternoon, half of which will be devoted to clotting. So hopefully, you can participate in that as well. So when -- I assume you're having some early conversations or maybe not, but early conversations with payers on milvexian. What are they setting the bar to be relative to whether they would embrace it as a new therapy?

No, it's a great question. We have had a number of discussions with payers sharing our target product profile compared to what we see with Eliquis. Although they haven't given us a specific threshold of what they want to see, they also recognize the value of a product that has comparable efficacy to Eliquis with a lower bleeding profile. They recognize the economic benefits, the significant cost savings that come with a lower bleeding profile. So don't lead to hospitalizations, increasing morbidity. And it's really the payers and employers that have to bear the brunt of those significant bleeding events. So they are looking forward to seeing a product that potentially can have a better bleeding profile than Eliquis, and we'll continue to have these discussions along the way to ensure that patients can gain access to this important product.

Well, so what is that, is that target product for bleeding profile [indiscernible] in shares.

Superior, obviously, to get on the market, we have to have a superior bleeding profile compared to standard of care Eliquis. And so we have put together our design paper. You've seen that. And so we do expect to see improvement in major bleeds versus standard of care Eliquis. That's the way we get on the market. And then we would expect to see an event rate -- an efficacy rate that is comparable to that of Eliquis.

So let's go on to another topic digging a little bit deeper into drug products that are on the come, but also on some of the products we just talked about. So how would you rank the following Bristol readouts in '26 and '27 by peak revenue potential? So [indiscernible], Cobenfy ,[indiscernible], iberdomide, [indiscernible] and Milvexian. So how would you rank them into their peak potential revenue-wise?

Well, I'm glad you mentioned 5 of the products and because all 5 will read out by the end of this year. All 5 have very strong commercial potential. And when you look at the 5 assets, you can just see the diversification of those assets from immunology to CV to hematology and to cardiovascular disease. So I'll touch briefly on each of the assets, and we can go as deep as you want, Steve, on them. So when I think about Cobenfy and [ ADP ], this is obviously a significant opportunity for the brand. I mentioned we've got 4 studies here. There's nothing approved in ADP.

And we think that the profile of Cobenfy can really transform an area that has seen nothing approved just using -- use of off-label antipsychotics. We just talked about the opportunity with milvexian, particularly in atrial fibrillation, the ability to beat Eliquis, which is a product that continues to grow steadily after over a decade on the market. That is another significant commercial opportunity for the company as well as for our partners in J&J. So we're looking forward to that data readout. Iber and Mezi, which is our 2 CELMoDs, we've got a lot of momentum coming out of ASH, and that's Iber, Mezi and Golcadomide.

You also know that we received recently our PDUFA date in a priority review from the FDA for iberdomide. So our PDUFA is now mid-August based on an MRD endpoint. So we also expect to see Iber and Mezi partnering with CD38 as well as with Kyprolis in earlier lines of multiple myeloma, also providing very good commercial opportunities over time. And finally, I think one of the sleeper assets that we don't talk enough about is admilparant. Admilparant is -- will be indicated for both IPF and PPF. These are fatal lung diseases. And when you look at the market today, it's about a $4 billion market.

We think the market can grow significantly over time. And a product like admilparant would not come with some of the baggage that we see with the products today, high rates of diarrhea, some other products that are coming to market that have high rates of cough or dyspnea, difficulty with inhalation type of mechanism. LPA1 or admilparant is an oral agent that has a potential opportunity to halt the progression of the disease while having minimal adverse events. So all of these are exciting opportunities, and we look forward to sharing the readouts at the end of this year, and they will all contribute to the growth at the end of the decade of this company, and our focus is really driving long-term sustainable growth.

We couldn't agree more. The IPF and PPF market does look very large. Could it be over $10 billion?

The way that we see it is it could at least double. Today, it's a $4 billion market. We think it could be between $8 billion and $10 billion. And how that would happen, it would happen with -- when you look at the diagnosis rates and treatment rates in IPF and PPF, particularly in PPF, they're incredibly low. In PPF, the treatment rate is only 30% today. So we would expect to see with newer agents coming to the market increases in both diagnosis and treatment rates. With a product like admilparant with an improved safety profile, you could see longer duration of treatment as it halts the progression of disease. We also see coming likely with the approval of admilparant, but also when I think about the next several years into 2035, the potential of combinations in this space, all of which will serve to grow the category. So what could be -- what is a relatively modest category today, we think could be a big category by the middle of the 2030s.

A competitor in the LPA1 space had a failed trial. So how is admilparant different? And how will it not suffer that same fat?

Yes. So we know that Amgen had a failure in the LPA1 program. Now a reminder, admilparant has a different mechanism of action. LPA1 is an asset that targets 3 specific pathways in the treatment of IPF and PPF. Amgen had what was called an LPAR1, which is different mechanistically. I think the second area that gives us confidence in our program is we had a very large Phase II program, about 400 patients in this program for IPF and PPF. And we saw significant improvement in [ FVC ] which is the primary endpoint of both our IPF and PPF studies, both strong efficacy as well as very good tolerability and safety profile. So taken together, we feel like those are really good reasons to believe in the enthusiasm that we have in this asset.

Maybe we can move to Opdivo and in its LOE. And the reason why I'm mentioning this is other companies with very large LOEs as well, including in the PD-1 space, have been more vocal with investors about their ability to push out the LOE and gain additional time on the market, and we're talking at least a year or much more. So why is Bristol not engaging in this conversation as well? I know you're a conservative company and so forth. But is there anything different about the IP estate at Bristol, say, versus your competitors who are being more vocal?

Here's what I'd say, Steve. Number one, as you just rightly pointed out, it's not our style to go out and talk about things that -- and potentially get over our skis in some areas that we are closely monitoring the case laws as it relates to patent exclusivity. What I will say is this, we will continuously to vigorously defend our IP, whether it's for Opdivo or any other product. We've been successful already in staving off biosimilars that are trying to come to market with Opdivo. And we do give 2028, December 2028 as our LOE as a conservative planning date.

That's what's in our long-range financial plan. I believe that's what's modeled in your long-range financial plan and should be the case, and we'll continue to update you as we look to the future. We do have subsequent patents for Opdivo that bring us out into the 2030s, but we are modeling December 2028 as the loss of exclusivity for Opdivo. But we also have, of course, we talked about Opdivo Qvantig, which could extend the franchise into the 2030s.

And what's really exciting is that by the time that we start to see the biosimilars coming into the market in the, let's say, the early 2029 period, we could also start to see some of our Pumitamig data come. And with Pumitamig, this gives us a potential opportunity to not just grow but expand the opportunity we have with IO, with our BioNTech partners. So we have multiple options around maintaining and growing our IO franchise into the future.

So let's drill on to Pumitamig. So why is the Bristol strategy in developing this asset better than that of competitors?

Look, I'm not sure if it's better than competitors. I mean, number one, we're very pleased with our partnership with BioNTech. They were very careful in selecting a PD-L1 VEGF. So note the mechanism difference. Now that has not played out, as you know, in the first-gen PD-1, PD-L1s. But when you look at adding a VEGF, we do think there's some mechanistic plausibility to an advantage that a PD-L1 VEGF could give. Number two is we've got a lot of experience in this space now, almost 2 decades, starting with the launch of Yervoy then to Opdivo to LAG-3.

So we've got experience from a scientific standpoint as well as strength commercially here. We have 8 Phase III studies that we have already announced that either started enrolling or will be initiating. And then with our BioNTech partner, we are excited because we've structured the deal and both companies have exciting assets in our early pipeline. So looking at novel, novel combinations, combinations with ADCs, combinations with targeted therapies. So you'll start to see more of that in the Phase I stage as we look to accelerate. Our goal is to be first or second in every tumor that we're going to compete in, save for lung where we know Summit has a clear lead there. But we feel very good about the partnership we have and the speed at which we're moving forward.

Sticking with the pipeline, but overall, not just in combination with Pumitamig, but what Phase I or Phase II assets across the Bristol-Myers Squibb R&D portfolio are you most keen to get your hands on to commercialize?

Yes. Well, as a commercial leader, there's nothing better than launching. And I said we've got the opportunity to launch at least up to 10 new medicines and 30 new life cycle management indications by 2030. And that's really this -- the wave of assets that are in Phase III or moving into -- rapidly into Phase III today. But the next wave, we just talked about Pumitamig in Phase III, but also we've got -- we'll start to move faster with Phase I novel, novel combinations. I think anti-Tau is another area. When you look into the 2030s, perhaps the neuroscience field could be the next oncology [indiscernible] where there's a huge unmet need there in Alzheimer's disease, in particular.

And our anti-Tau, which is in Phase II today, we've got a number of really promising assets in neuroscience, but also specifically in Alzheimer's disease, products with Brainshuttle technologies, new mechanisms, combinations that we're really excited to bring forward. In the oncology space, -- very excited to launch a product like PRMT5. Now we have 2 studies in Phase III. As you know, MTAP deletions are prevalent in about 10% to 15% of most cancer types. So many of those studies are already in Phase I, and they'll be moving into Phase III after proof of concept in monotherapy and in combination.

And then I'd also say, iza-bren, we just announced study that was done in China in triple-negative breast cancer. And in triple-negative breast cancer, iza-bren, which is our HER3 EGFR ADC that we partnered with Systimmune and showed both an overall survival and a PFS benefit in monotherapy. So just think about what that could mean in combination in areas like lung cancer, EGFR mutant lung cancer or triple-negative breast cancer and a host of other different cancer types. So these are just a few examples of assets that we're really excited.

We've got a significant number of assets that are in Phase I today or moving into Phase I, Orbital being another example where we could possibly -- we're possibly looking at curing patients or at least having durable remissions in some of the toughest to treat autoimmune diseases. So we've got a real significant number of assets that are coming behind these Phase III data readouts.

We -- try to end all our panels by asking, what do you think the biggest surprise or change will be at Bristol-Myers Squibb in the next decade?

Yes, I love that question, Steve. Thanks for asking. Well, I think the #1 surprise for Bristol is not a surprise to the Bristol management team, but I think it's going to be a surprise to many of the analysts out there around how you're modeling growth for the company at the end of the decade. When Chris became CEO in 2023, he set out a clear vision for this company. And that is to be the fastest-growing company at the end of the decade. We want to see top-tier long-term sustainable growth.

And when you look at the number of assets that we have, we talked about so many of them this morning, whether it's from Cobenfy to milvexian to [indiscernible] to Arlo-cel, which is our GPRC5D to our CELMoD platforms to products that are moving very rapidly into Phase III to our radiopharmaceutical platform, all of these substrates are going to provide significant growth. So I'm looking forward to sitting here, Steve, a year from now, and you'll just see a good piece of the readouts that we have as a company. But we feel really good at Bristol-Myers Squibb about where we will be as a company and the growth trajectory we'll have from '29 to the end of the decade and driving long-term sustainable growth and what that means to the company, to our shareholders and importantly, to patients.

I have to say it's an impressive amount of momentum in the product story. So sadly, with that, we do need to conclude. We are out of time. So Adam, thank you so much for making the time to be with us.

Thanks for having me. Thanks for the great questions.

Welcome to Bristol-Myers Squibb Fourth Quarter 2025 Earnings Conference Call. [Operator Instructions] Please note, today's 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 2025 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. 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 2024 and sales growth rates will be discussed on an underlying basis, which excludes the impact of foreign exchange. All references to our P&L are on a non-GAAP basis. And with that, I'll hand it over to Chris.

Thanks, Chuck. Welcome, and thank you for joining us this morning. 2025 was a year of focused execution across the business. We believe our results further demonstrate the ongoing strength in our growth portfolio as we advance our multiyear plan to rewire BMS for long-term growth. These efforts enabled us to enter 2026 with good momentum.

Let me start by highlighting our recent progress on Slide 4. We closed the year with strong fourth quarter performance. Our growth portfolio grew 15% year-over-year in Q4 and 17% for the full year.

In terms of building out breadth with newer products, Opdualag, Breyanzi and Camzyos each contributed over $1 billion in sales for the full year, while Reblozyl delivered over $2 billion. These are differentiated durable products early in their life cycles with meaningful runway ahead that further strengthened the foundation for long-term growth.

And on a full year basis, it is worth pointing out that despite a decline of roughly $4 billion in revenue from our legacy portfolio, the growth portfolio nearly offset all of that. Cobenfy and Qvantig also continued to progress well and in line with our expectations. With Cobenfy, we saw steady growth as we expanded access and deepened adoption across community and hospital settings. And we expect this steady growth to continue throughout the year. Qvantig continued to receive positive early feedback from users with improved practice efficiency and patient preferences as the main drivers. David will provide more detail on our portfolio's performance shortly.

Turning to recent clinical and regulatory highlights. In December, Breyanzi received FDA approval as the first and only CAR-T cell therapy for adults with relapsed or refractory marginal zone lymphoma. It is now approved across five cancer types strengthening its leadership position among CD19-directed CAR-Ts.

In December with our partners at BioNTech, we also shared the first global Phase II data for Pumitamig in locally advanced or metastatic triple-negative breast cancer. These data showed encouraging antitumor response and a manageable safety profile in both the first and second line treatment settings. Triple-negative breast cancer remains an aggressive disease where there is an urgent need for new treatment options. And within the overall Pumitamig development partnership, we recently announced three additional planned studies, resulting in eight registrational studies we expect to have underway by year-end.

We are pleased to announce that two of these studies in non-small cell lung cancer are now initiating in [ unresectable ] Stage III disease and in first-line high PD-L1 expression.

We also just posted details regarding our global Phase III study, break-free SSC for Zola-cel, our CD19 CAR-T, now initiating in patients with active systemic sclerosis.

Finally, we very much look forward to the first oral day presentation for navlimetostat, a potential first-in-class PRMT5 inhibitor. This will be combination data in the pancreatic setting and will be showcased at the ESMO Targeted Anticancer Therapies conference next month.

These milestones reinforce the momentum of our pipeline with more readouts to come this year, which I'll talk about on Slide 5.

As we shared last month, this is a data-rich period for BMS, which could drive the introduction of more than 10 new medicines and over 30 meaningful launch opportunities by 2030. The increasing pace of pivotal readouts later this year will serve to better define the potential of our pipeline candidates. We are confident in our ability to deliver an attractive and durable growth profile heading into the next decade.

The breadth and depth of these opportunities is illustrated on this slide. This year alone, we expect to report top line registrational data for six potential new products, milvexian in both atrial fibrillation and secondary stroke prevention, admilparant, an idiopathic pulmonary fibrosis, iberdomide where we have already demonstrated a significant improvement in [ MRD ] negativity rates, mezigdomide and [ arlocell ] in relapsed or refractory multiple myeloma and raise 101 in second line plus gap nets.

We also anticipate meaningful pivotal line extension readouts for Sotyktu in lupus and Cobenfy Alzheimer's disease psychosis.

Most of these readouts will occur in the second half of the year, and we have more data readouts coming beyond 2026. Together, these represent an attractive set of near-term catalysts that can meaningfully enhance the long-term growth profile of our current growth portfolio.

We communicated at the start of last year that getting the long-term right means executing well in the near and medium terms. As you can see from our results, we continue to deliver across the organization in 2025, maintaining this strong say-to-do ratio by consistently delivering on our commitments has now been embedded in our culture, and will continue to be core to how we operate.

As you have seen in our financials, we delivered on our cost savings initiative in 2025, and we'll continue to expand the use of AI to help us move faster, operate leaner, and reinvest strategically in growth.

Our financial strength continues to allow us to invest in our business and bring exciting science into the company through the pursuit of high return business development. Our North Star remains to deliver industry-leading sustainable growth into the 2030s and beyond.

Now let me give you a high-level overview of our 2026 guidance on Slide 6, and David will speak to it in more detail shortly. We currently anticipate 2026 revenue in the range of $46 million to $47.5 billion. This range reflects continued strong performance from our growth portfolio and a projected revenue decline for our legacy portfolio of between 12% and 16% given the ongoing LOE impacts.

Within the legacy portfolio, we project Eliquis growth this year to be in the range of 10% to 15%. This is driven by continued global demand growth and the recent price reduction which expands patient access and eliminates the associated inflation penalty. We expect lower operating expenses compared to last year due to our ongoing cost savings program, and we expect adjusted diluted earnings per share of between $6.05 and $6.35. With that, I'll turn it over to David.

Thank you, Chris, and good morning, everyone. I will begin my review of our 2025 financial results, focusing on our fourth quarter performance. I will follow up with the introduction of our non-GAAP financial guidance for 2026, and some considerations to help you better understand our financial outlook for this year.

We had very strong commercial and financial performance in 2025, marked by focused execution on driving top line growth and generating strong cash flow while strengthening our balance sheet and continue to manage our cost structure. We've entered 2026 in a position of strength with a solid foundation, which we can continue to build upon to deliver on our long-term growth strategy.

Starting with Slide 8. Total revenue in the fourth quarter was flat year-over-year at approximately $12.5 billion. Our growth portfolio continued its positive momentum with revenue increasing 15% to $7.4 billion, representing close to 60% of our total revenue in the quarter, key brands, including Reblozyl, Breyanzi, Camzyos and our [ IO ] portfolio all achieved significant growth and were further supported by our early launches of Cobenfy and Qvantig.

Within the legacy portfolio, higher revenue from Eliquis was offset by continued impact of increased generic volumes across several other brands. All in, we are very pleased with the results in the fourth quarter and full year as our growth portfolio performance continues to reshape and redefine BMS as we strive to be one of the fastest-growing pharmaceutical companies into the next decade.

Turning to product performance on Slide 9, starting with oncology. OPDIVO again delivered solid growth in the fourth quarter, with revenue up 7% to nearly $2.7 billion. This was driven by new indications and continued share growth within the first-line non-small cell lung cancer setting. Qvantig launch continued to progress well with revenue of $133 million in the quarter. With Opdualag, we delivered another quarter of strong double-digit growth, driven by demand in the U.S. where it remains a standard of care in first-line melanoma.

Turning to Slide 10. Reblozyl delivered 21% growth with performance reflecting solid uptake across first and second line MDS-associated anemia patients. Over the past 2 years, we've delivered a very strong launch for Reblozyl.

In cell therapy, Breyanzi fourth quarter revenue continued to show impressive growth with revenue up 47%, driven by its desirable profile and continued strong demand across its approved indications. We continue to be encouraged by Breyanzi's growth prospects into 2026.

Moving to cardiovascular on Slide 11. Eliquis delivered nearly $3.5 billion in the fourth quarter revenue, an increase of 6%. This was driven by demand growth and market share gains with the U.S. revenue increasing 4%.

Turning to Camzyos. Revenue in the fourth quarter grew 57% to $353 million, benefiting from continued demand growth globally. In the U.S., we expanded the number of physicians who are prescribing the drug. And outside of the U.S., we have now launched in over 50 countries.

Now moving to immunology. Global revenue of [indiscernible] to grew 3%. We look forward to our upcoming PDUFA date for psoriatic arthritis and our Phase III readouts for lupus and [ shogren's ] disease. I will wrap up by reviewing our product performance for the quarter on Slide 12 with neuroscience.

Cobenfy fee revenue in the fourth quarter was $51 million, with continued steady uptake among prescribers and patients. Cobenfy uptake has surpassed all schizophrenia comparators and relevant analogs in the first year of launch, and we continue to expect steady growth throughout the year.

Let's move to the P&L on Slide 13. As expected, gross margin declined 210 basis points in the fourth quarter to 71.9%, driven primarily by product mix, notably Eliquis and [ Revlimid ]. Regarding our operating expenses, we made significant progress during 2025 against our $2 billion strategic productivity initiative. As of the end of the fourth quarter, we delivered on a target of approximately $1 billion in savings in 2025 and are on track to realize the remaining $1 billion over 2026 and 2027.

Excluding in-process R&D, operating expenses for the full year were $16.6 billion, a decrease of $1.2 billion from 2024. This reflects our ongoing cost savings program, partially offset by continued investment behind growth initiatives.

Our effective tax rate in the quarter was 22.1% and compared to 19.9% in the prior year, with the effective tax rate in 2025, reflecting the onetime nontax deductible in-process R&D charge related to the [ Orbital ] acquisition.

Overall, diluted earnings per share were $1.26 for the quarter. And full year diluted earnings per share came in at $6.15 and both include a net charge related to in-process R&D and licensing income, which totaled $0.60 per share in the quarter and $1.40 for the full year.

Now turning to the balance sheet and capital allocation highlights on Slide 14. Our financial position remained strong with approximately $11 billion in cash equivalents and marketable securities as of December 31, 2025. We completed our targeted $10 billion of debt paydown ahead of schedule and generated strong cash flow from operations of approximately $2 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 top priority, while also returning cash to shareholders through our commitment to the dividend.

Now let me walk you through our non-GAAP 2026 guidance on Slide 15, starting with revenue. As Chris mentioned earlier, we estimate revenue to be between $46 million and $47.5 billion in 2026. We expect our gross margin to be between 69% to 70%. This reflects the impact of product mix, notably the combination of higher Eliquis and lower Revlimid and Pomalyst revenue. We expect total operating expenses to decline from 2025 levels to approximately $16.3 billion.

Our cost savings program has provided us with the flexibility to increase commercial investment where appropriate and to support newer development programs, such as our partnership on Pumitamig and our [ Orbital ] Therapeutics program. Even with these investments, we expect to reduce costs year-over-year.

We are expecting our OI&E expense of approximately $700 million, which reflects the expiry of our royalty-bearing license of diabetes products at the end of 2025. 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 $6.05 to $6.35.

Before closing, let me provide some insight regarding our expected quarterly progression of revenue for 2026. As it relates to quarterly phasing, we expect our typical sequential revenue decrease in the first quarter due to the seasonal inventory destocking we see each year following the build in the fourth quarter. And two points on Eliquis. First, we anticipate that the second half revenue will trend higher than the first half of the year. And second, in terms of Eliquis specific updated guidance, we currently expect 2027 Eliquis sales compared to 2026 and to show a step down in the range of $1.5 billion to $2 billion, which is broadly consistent with analysts' existing estimates.

In closing, our strong performance in 2025 demonstrated our confidence in our ability to deliver long-term value for our patients and shareholders. We remain focused on executing our growth strategy, advancing our pipeline and optimizing our cost structure. We look forward to updating you on multiple data readouts this year. And with that, I'll now turn the call back over to Chuck for Q&A.

[Operator Instructions] And today's first question comes from Seamus Fernandez with Guggenheim Securities.

Great. Congrats on the good quarter and the guide. Now that we're past the guidance, this is a question for the overall team, but it's been a long time since we've seen as an overall analyst community a series of Phase III pivotal catalysts that Bristol has ahead of it in 2026.

Chris, I know you counted six There may be, in addition to that, potential benefits from royalty agreements around sotatercept and [ cadence ]. Just wondering if you could help us position the areas that you see the most kind of relative upside the CELMoDs are obviously something that Bristol has been working on for a very long time, and we're just on the cusp of seeing the material data we've got milvexian and a very different approach that Bristol took to dosing and a recent publication that plays along those lines to sort of explain that. Admilparant, I think is an underappreciated story that was maybe negatively impacted by comparisons to a competitor asset.

There's just a whole host of opportunities here that we see in the overall story this year. Hoping you might be able to help position some of those for us as we move through the balance of the year?

Thanks for the question, Seamus. And I agree with the overall sentiment and maybe I will start and then I'll turn it over to Cristian and Adam and they can provide their perspectives.

I think that when we look at what's particularly exciting for this year, I would highlight a few things. First of all, we've got good growth just in the products that we have on the market today, and I think that growth is going to continue into this year. As you know, we have a slew of data readouts coming this year now just a few months away for six products. And when you look at the actual number of Phase IIIs, we could have over 10 Phase III data readouts this year alone with more coming in '27 and then another big slew of them coming in 2028.

The things that I think stand out for me, you've already mentioned them actually, the CELMoDs program is beginning to bear fruit. We've already demonstrated PFS data for iberdomide. We'll see follow-up data on that with PFS this year. We've got admilparant data coming. We've got the milvexian data, and I agree also with your assessment of that where I think we'll see the SSP data from a competitor today. But as I look at our profile, I think we have the potential to be best in class there.

And of course, in AFib, we have the potential to be the only Factor XI oral therapy there, which is obviously a big opportunity. But maybe I'll ask Cristian and Adam to quickly add anything to that.

So thank you, Chris. Thank you, Seamus, for the question. Let me go a little bit more on the technical side because as you said, we have a very data-rich year with 10 -- at least 10 pivotal readouts. I like to cluster them also in terms of area, therapeutic areas.

In hematology, I think you mentioned [ excaliberia verdone ], we will have the PFS. MRD is already readout positive. We've shared the data because, of course, the PFS was coming, we wanted to preserve the integrity of the study. But we are very confident that what we have seen in MRD can translate and benefit in PFS. We will have the second sell motor readout, [indiscernible]. And this is an add-on study. We had a [ messi ] on top of KD -- versus KD. So considering the level of activity we have seen with this drug, I am confident on the first readout with the second cell model, a very potent drug.

And then we have also [indiscernible]. [indiscernible] is a Phase II registrational study, the Phase III is ongoing in myeloma in patients post [ BCMA ], a GPRC5D CAR. This is an entry with another CAR that is very, very relevant for us. So myeloma very rich, I am very, very confident in what we have seen so far and what I'm expecting.

Then we go into, as you said, admilparant, I'm very happy because what I have seen is a Phase III conducting and enrolling patients that are very similar to what we have seen in Phase II. And you remember, in Phase II, we had a very good reduction of the risk of decline of [ FVC ], 60% in IPF and more than 70% in PPS. So IPF is coming this year. PPS is closer, actually, will be very, very closer compared what we guided before. So this is very exciting, very high medical need.

Milvexian, think Chris already spoke about stroke has already been derisking my view from the data we will see in a few hours. There is no reason to believe that we will have a different better outcome. And the AI, the confidence is all there. Then I would not underestimate our [indiscernible] program. The [ ADAPT ] program is coming by the end of the year, as we guided, we are on track. All of this is moving at pace. So as you said, four different therapeutic areas where we'll have a major readout and these are very transformative regimen. Adam, do you want to?

No, I think, Cristian, you covered it extremely well. So why don't we go through the next question. .

And our next question today comes from Chris Schott at JPMorgan. Please go ahead.

Just two for me. First just elaborate on Eliquis dynamics for 2026 contributing to growth this year? And then maybe just a bigger picture one on business development priorities. Just to elaborate a little bit more in terms of your focus right now, is this more on deepening presence in existing therapeutic areas or maybe pursuing more [indiscernible] like kind of expansions into new spaces? And maybe as part of that, I know, as you just highlighted, you've got a lot of important readouts coming this year. Should we think about Bristol waiting to see how these programs pan out and that might help guide where you want to go with BD? Or is that not a rate limiter for the company?

Thanks for the question, Chris. I will start on the BD question, I'll turn it over to Adam. So as was said earlier, BD continues to be a top priority. As you well know, we have always sourced innovation, both internally and externally. And the good news here is that we're in a very strong position, as you alluded to with the late-stage pipeline. We don't need to chase deals, that said, we're going to continue to be looking out for opportunities to add strength and depth to our portfolio.

In terms of the opportunities we're looking for, we've got a lot of opportunity to continue to build depth across each of our therapeutic areas. So if an opportunity is in an area that we know well scientifically where we can add clinical or commercial value and ultimately deliver that value to patients, the company and shareholders. We obviously have the financial ability and the muscle to execute. And so that's generally how we'll be approaching BD this year. And timing wise, I think that, obviously, we're going to be opportunistic.

Yes, Chris, thanks for the question. Let me start by saying that we continue to see strong performance with Eliquis, and this performance will continue throughout 2026. We have approximately 75% [indiscernible] share in the U.S., and we will continue to grow that.

Now the broader pricing dynamics starting this year for Eliquis was the impetus for us to reevaluate our pricing strategy. And of course, there's some pushes and pulls. Recall the IRA price was effectuated January 1, and this includes the removal of the Medicare Part D liability both in the initiation and in the catastrophic phase.

We also finalized our $0 Medicaid agreement with administration. And we took a step back and were able to reassess our commercial contracting strategy as well. The roughly 40% WACC reduction eliminates the inflationary penalties or CPI penalties of statutory rebates that have been accumulating over many years for the brand. And taken together, the continued increase in Eliquis market share in the United States, coupled with these net pricing changes, they can enable Eliquis to be an important driver of growth this year.

And our next question today comes from Michael Leuchten at UBS.

Two questions, one on milvexian and AFib. Previously, you've suggested that there are lower blinded safety event rates bleeding, particularly. Can you just remind us how often that study is looked at and whether that generally continues with [ DSMB ] safety looks across the blended rates into 2026 here and how you feel about that?

And then second, just following up on the BD question. I know that you obviously want to focus on key strength areas is metabolic obesity a fair question or a fair area that investors should be understanding of? And is that still an area that actually you would engage in.

Thanks for the questions. Let me start with metabolics and then I'll turn it over to Cristian. Look, metabolics is obviously an exciting area. You've seen it this week. We continue to pay attention to the evolution of that market and of course, the science. That said, we're really looking at opportunities to build breadth and depth in our existing therapeutic areas. These are areas we obviously know well. We can assess the science and commercial opportunities, which is significantly important particularly as we think more broadly. And it's also an area of the areas that we can best add value from a patient, company and shareholder standpoint. So that's our primary focus. Cristian?

Thank you, Michael, for the question. As you know, we completed the enrollment in [indiscernible] atrial fibrillation study. We have more than 20,000 patients, and we well passed the point for instance, in which [indiscernible] atrial fibrillation study was terminated by the DMC because of lack of efficacy. .

And as you said, the DMC regularly continue to endorse the tire progression, and this happened also very recently. They check efficacy and safety. We remain blinded to the study. What I can tell you is that recently, and there is a lot of data that tell us what is the bleeding rates with us. And in an API study is a [indiscernible] milvexian and Eliquis. And we remain blinded, but what thesis telling us and what we see in a blinded fashion in terms of bleeding base, give us confidence that we are still very much on target to achieve the benefit that we hope showing that Eliquis and milvexian are similar in terms of efficacy, but that [indiscernible] can bring a benefit in reducing importantly the bleeding risks, major bleeding risk is also no major clinical elevating risks. These -- we are fully on track on this and the study is coming this year.

Our next question today comes from Courtney Breen with Bernstein.

I just wanted to double click on Eliquis question as well as on cost savings in '26. I know your intention is to take more cost savings in the '26 period. And so it would be great if you can kind of perhaps characterize those relative to what you're able to achieve through the year 2025.

And then on Eliquis, thanks for giving the details around kind of some of those 2026 dynamics. I think you made some additional comments on that '26 to '27 transition of $1.5 billion to $2 billion started to step down. Can you just help us understand kind of what is driving that primary change at that moment in time relative to this new baseline on pricing that we've just spoken through now.

Thanks for the question, Courtney. I'll ask David to take hold and go from there.

Yes. So on the cost savings program, as you saw this year, we made really great progress against the $2 billion strategic productivity in the shift, achieving over $1 billion of that. And sitting here today, we got really solid line of sight into the additional $1 billion, which will be spread over '26 and '27.

So you'll continue to see a step down in our expense base. What I'd also say is it's also enabled us to reinvest in growth drivers, some of investments we did last year with Cobenfy as well as Camzyos but also with a couple of the deals that we did with [ Orbital ] Therapeutics as well as minima, we'll be annualizing those costs here in '26, and we're still reducing our cost base as a result of that.

Adam, do you want to just hit on Eliquis dynamics this year and then you and David can speak to '26 to '27.

Yes. So I spoke about the Eliquis dynamics, as Courtney said, around the pricing changes that took place effective January 1, including the removal of the Medicare Part D liability and the 40% WACC reduction. So we wanted to guide against the 2026. David will talk about our decision not to guide for 2027, which had started Chris initially became CEO in a decision not to provide longer-term guidance. And David, do you want to expound?

Yes, Courtney. And thanks for your question. If you remember back in August 2024 when the irate came out, there's a lot of questions about what that impact was. So we provided guidance at that point in time. We thought it was important just to update you on that '27. So what we said this year is that we expect Eliquis to grow 10%, 15%. And as you think about next year in my prepared remarks, I said that you should expect a similar step down about $1.5 billion to $2 billion from '26 to '27, which is consistent with the step-down consensus as now. So hopefully, that's helpful.

And Courtney, just a reminder, Chuck here. Remember, the EU patents largely expire late in '26. So that's going to be a factor in '27 that we'll see as well in terms of driving the step down.

Our next question comes from Mohit Bansal with Wells Fargo.

I have a question on LPA1. So from the feedback we have received from some KOLs is that the toxicity burden that is associated with the existing standard of care. Combo therapy may be reserved for more severe patients and for the widespread use of LPA1 monotherapy, patients may still want to see some kind of efficacy benefit over existing therapies here. I don't know how you are thinking about it, but would love to get your thoughts on like what it takes for a new therapy like LPA1 to become a new steroid either as a monotherapy or a combo therapy in this space.

Thanks for the question, Mohit. Adam?

Mohit, thanks for the question. So IPF and PPF are progressive pulmonary diseases and prognosis for these diseases is not dissimilar to what we see with some metastatic cancer diagnosis. In fact, there's less than 50% 5-year overall survival rate. So there's a significant need for newer therapies that provide greater efficacy and tolerability.

What we're excited about with admilparant, which is our LPA1 is that this is a potential first-in-class product that we believe could redefine the standard of care in pulmonary fibrosis, offering improved efficacy and improved tolerability profile. Remember, no product works by slowing the progression and could actually potentially halt the progression of disease.

And we look at the adverse event profile, we're seeing low rates of GI tolerability, which has been a real challenge for some of the older therapies as well as some of the newer therapies that have recently introduced to the market to help manage their disease. In fact, about 50% of patients abandoned treatment by 12 months.

We've also seen some newer agents have some formulations that may limit uptake. So we would expect to see admilparant used in combination of -- and as a monotherapy similar to how we're studying the drug and we really look forward to the data readout in the second half of this year.

And our next question today comes from Terence Flynn at Morgan Stanley.

I just had two. One is just on the milvexian AFib study, Cristian, wondering if you can speak to what you view as a clinically meaningful delta versus Eliquis, that would be enough to support broader payer coverage there.

And then just, David, on the guidance, the math that we're doing suggests kind of mid-single digit growth year-over-year on the growth portfolio, which includes OPDIVO. So I just want to know that we're in the right ballpark there.

Thanks for the question, Terence. Maybe Christian and Adam combine on milvexian and then David.

Thank you, Terence, for the question. The study primary endpoint is showing non-inferiority versus Eliquis, [indiscernible] on efficacy. And Terence,we selected those that is -- was very scrutinized to balance activity, potential activity and, of course, bleeding risks. This is why we are using 100-milligram BID. It is a dose much higher than for instance that we use in stroke prevention.

So I would say there is a possibility that, of course, milvexian show a better outcome, but the real and present point is showing non-inferiority. Let's not forget the [indiscernible] AFib actually did not -- was able to show that level of similar activity versus [indiscernible].

Then after the non-inferiority will be met, we're going to test a superiority for bleedings. So this is also where we wanted to show a clinically meaningful differentiation on the bleeding rates.

I don't give you the deltas and everything. Of course, we believe that if the study will be a target that will be seen as a clinically meaningful. Adam, do you want to?

Yes. Terence, thanks for the question. So milvexian represents a significant commercial opportunity, particularly in AFib. AFib is a very large market, and we believe that milvexian the potential to replace first-generation [indiscernible], and this is a market that we know very well.

Fear of bleeding continues to be the main reason why clinicians hold back from using Factor X in more patients. Roughly 40% of patients remain either untreated or undertreated leaving them at risk for a stroke, and they had significant concerns around bleeding we know safety is important. We believe a differentiated bleed profile will drive demand versus standard of care.

We've had a number of [ payer ] discussions already. That suggest that the potential of improved benefit risk profile will be a strong value proposition. And we would also expect there to be an economic benefit of using mill vaccine over Eliquis in terms of bleeding events that are avoided. So we look forward to the data readout at the end of 2026. And we're confident this product has multibillion dollar potential.

Yes. And Terence, you're absolutely right in your math in thinking about the growth portfolio. We feel really good about the growth portfolio, mid-single-digit growth. But also we have the risk of rent generics coming this year, which would impact that growth portfolio. But we feel really good about where we exited '25 and about the process heading into '26 now.

And our next question today comes from Geoff Meacham from at Citi.

Great. everyone. Thanks so much for the question. I have a couple. So one for Adam, I guess, on Cobenfy. There's a lot of excitement earlier last year, you just give it some mechanism and lack of innovation in the category, but we really haven't seen an inflection point in sales. I guess, is there a bottleneck in access that you really have to still work through? I'm just trying to figure out the steps to see sequential acceleration.

And then on Pumitamig, I guess maybe for Chris or Cristian, is there a data set, a tipping point, maybe of data that you want to see before you really scale up the Phase III investment, just given its foundational mechanism, what's the upper end of either Phase III studies or tumor types that you ultimately have a capacity for the drug?

We'll start with Adam, and then Cristian can handle the Pumitamig question.

Great. Thank you, Geoff. So we're pleased with the progress that we made in Cobenfy's first full year on the market. In fact, Cobenfy delivered over 100,000 TRxs since launch, and that surpassed all relevant schizophrenia analogs.

We have very strong access, virtually 100% access across Medicaid and Medicare. And now we're approaching 70% commercial access. So that is certainly not a bottleneck. We made good progress in Q4 as you were able to see with an acceleration of NRxs as well as increases in both new NRP trialists after our full field force expansion was in place in both the community and the hospital.

So we see continued opportunity for growth in schizophrenia as we stated, we're confident in our ability to deliver continued steady growth and new indications are going to be the driver of inflections there. But we hear from physicians, the feedback continues to remain positive. We are making very good progress with adding the number of trialists, which continue to grow steadily. And importantly, what we have seen is that those physicians who've had a positive experience with Cobenfy have shown an increased propensity to repeat prescribing.

So this year, we'll present several new Phase IV studies, including a switch study later on in the quarter, which is the top question that we get from physicians on how to switch from a D2 over to Cobenfy we'll have real-world data as well to support that, and we're increasing investment in peer-to-peer activities.

So taken together, we are making good progress. And based on all the leading indicators we're seeing, we believe Cobenfy has the potential to become a leading treatment in schizophrenia over time, and we're confident this could be a big drug for the company.

Thanks for the question, Geoff. The -- let me break down your question. The first thing is the confidence. First of all, we have data sets in triple negative and in small cell lung cancer, showing that the drug is active. And there are also very large data sets from competitive assets that reinforce the message.

The second thing is more on -- these are two very well clinically validated targets, PD-1, PD-L1 and the VGF. And you know that when you deliver [indiscernible] bispecifics, sometimes you increase the selectivity and this can be even more powerful the just delivering the two makers -- two different drugs.

Then when you look, we are actually already scaled up development of this drug. The confidence is very high. We believe the strategy is very simple. We want to replace and then we want to expand. We want to replace where PD-1, PD-L1 inhibitors are playing today in those indications through this bispecific. And then we want to expand because we believe bringing VGF on top of PD-L1 inhibition, we can also we can also tackle some of the indications where PD-1, PD-L1 inhibitors are not working well enough or not at all.

So this is the reason why we already have started or are in flight to start seven pivotal studies across multiple indications. And there is a one that we announced in the neck. And when you look at the indication. We -- of course, there is a concentration in small cell lung cancer, a very important indication, this goes beyond, gastric, colon, head and neck, breast. So this is a program that as a top priority in oncology, and we represent the backbone of our portfolio.

The next wave will be to novel [indiscernible], and that will be the next wave of studies where we will continue to improve on regimens that we are creating today.

And our next question today comes from Asad Haider with Goldman Sachs.

Most of my questions have been answered, but maybe one for Adam. Just any update on how the Opdivo subcu formulation launch is progressing. We've had four quarters on the market now, two with the [ J-code ]. Do you believe you're still on track for the 30% to 40% patient conversion by 2028? And any color on the types of patients who are utilizing it would be helpful.

Great. Thanks, Asad. So we're very pleased with the Qvantig launch performance in its first full year on the market. We're encouraged as we're seeing use across multiple tumor types we're seeing uptake across monotherapy indications as well as in the combination setting. So patients who are treated for RCC, GI, metastatic melanoma.

As you said, we did receive our permanent J-code last July, which eased the reimbursement process for physicians. And post that, we've seen a nice acceleration of new accounts adopting. We're focused on continuing to drive depth and breadth of account conversion and reinforcing the benefits that we know are there for both practices and for patients. And we're tracking well against our expectations and remain very confident in our expectation that physicians will convert 30% to 40% of the ID business ahead of the LOE. So we're pleased with the performance and what this means for patients and for physicians.

Our next question today comes from David Risinger with Leerink Partners.

So I have two questions, please. First, with respect to admilparant, could you just talk about the hypertension risk and how you would contextualize that for us?

And then second, it would be helpful to just better understand what is in the guidance and what you're assuming for generic competition. So for Eliquis, could you just talk us through when you're expecting generic entry in major markets ex U.S. in '26 and '27.

And then for Orencia, how many players do you anticipate launching and when?

Thanks for the question. I'll ask Cristian to start and then David.

Thanks, David, for the question. The hypotension as [ syncopal ] episodes, is -- was one of the tolerability risks that we had with [indiscernible] in the Phase II. But what I can tell you that actually, in the context of the Phase III, this is going very well. Let me give you a little bit more context.

When we run the Phase II, we tested two doses, 30 and 60 milligrams. And of course, there was a dose relation outcome in terms of efficacy also safety. But then when we completed the study, we have seen that the risk of [ syncopy ] was well managed. And actually, we decided to -- because there was a dose relation on efficacy, we decided to introduce in the Phase III, 120 milligram. And actually, we are running the Phase III studies, IPF and PPF with 120 and 60. And the 120 that was [indiscernible] just to assess the safety and the risk of hypotension the DMC allowed us to go in Phase III and in a blinded fashion, we didn't see any rate that raise any concerns.

So this is definitely associated to the profile of the drug is very well managed even when you go with a higher dose, that, of course, can translate to a better efficacy.

Yes. Just to add, Cristian, what we're hearing from physicians is that this is a very manageable side effect. And when you look at the totality of the drug, not only have we seen exciting results around FCC. But I talked about earlier, when you look at the rates of GI toxicity that have really plagued some of the assets that are out there today as well as some of the newer products that are coming to the market that have significant cough issues or dine issues that can lead to significant exacerbations. I think we have an opportunity to truly be a best-in-class product, both from an efficacy and a safety standpoint. David?

Yes. And the question on [indiscernible], I talked about it in total, that $1.5 billion to $2 billion step down as we go into '26, and that is driven by generic entries that we're assuming are going to happen. It's really spread throughout. It's a country-by-country basis on how that goes in. We're in litigation. We're in appeals in several of those markets. So we have to see how that plays out. But we made broad-based assumptions about generic entry.

And I think in the last part of the question, David, was around Orencia. So Orencia continues to perform well with great cash flow for the organization. As far as a biosimilar for Orencia we do know that [ Dr. Reddy ] Labs has posted an opportunity to file. The manufacturing facility is out of India. And we had this product now since 2006, and we recognize the challenges that it takes to manufacture a product like Orencia. And so we do expect to see continued cash flow from this important product for patients.

And Dave, I would just underscore in the EU is country by country, for sure. The bigger countries are clustered around late in the year in the November time frame late in the year. And with that, can we go to next question, please?

Absolutely. Our next question today comes from David Amsellem with Piper Sandler.

So I wanted to ask about Cobenfy and a bigger question. There are a number of companies developing their own [ M1M4 ] and in some cases, without a peripherally acting anticholinergic. So I wonder how you think those agents down the road could impact Cobenfy growth, if at all? That's number one.

And then number two is, can you just talk more to how big of a priority is it to add a late-stage or commercial ready psychiatry-focused asset or assets where you could leverage the commercial infrastructure that you've built to support Cobenfy? Again, how big of a priority, how aggressive do you want to be here?

Well, let me start on the business development question, then I'll ask Adam and Cristian to address the specifics of Cobenfy pipeline question or a competitive question.

So from a business development standpoint, as I said earlier, our focus is on continuing to build out breadth and depth in each of our therapeutic areas. Obviously, we've shown a willingness to do business development to build out our presence in neuroscience. And I think you can expect that if there are attractive opportunities where the science is compelling and where the financials allow us to add value to the company and ultimately, to shareholders in the neuroscience space, we would certainly be looking at it. Adam?

Yes, thanks for the question. When we were doing the work for [ Karuna ], we were really excited by the novel mechanism of action, not just the fact that it was working on most [indiscernible], but the fact that the [ M1M4 ] component of that, which we saw brings an opportunity for increased and improved cognitive benefit and schizophrenia as well as negative symptoms. And we're seeing that in the market today.

Additionally, when you look at the incredible life cycle management program that we have in place with significant number of studies that are ongoing in Alzheimer's disease, in Alzheimer's psychosis, Alzheimer's disease cognition as well as agitation, coupled with bipolar disorder, this has the opportunity to be a very significant drug in the neuropsychiatric space.

And we also have a very significant head start on other competitors coming. And I'll turn it to Cristian to talk about Cobenfy and also the pipeline as well that we have from the [indiscernible] acquisition.

So David, you raise an important point. There are many -- there are M4 agonist that are M4 [indiscernible] PAM, Positive [indiscernible] Modulators. You have other M1M4 that are emerging. First of all, we are ahead of everybody else. This is the first point. The second is we still don't know how M4 agonist or M4 PAM can play out versus an M1M4 inhibitor like Cobenfy. And we don't still don't know if you change your peripheral radical energic drug, how this can impact the brain penetration and additional -- the control of some of the cholinergic symptoms.

We believe that Cobenfy with [ xanomeline ] and [indiscernible] has the right approach. As Adam said, we have a very rich pipeline coming from Corona from our internal research that, of course, keep investigating these mechanisms. And we will disclose the right time how these programs are progressing, and we are focusing very much on these receptors. And of course, we have assets that go beyond that because some of them are as to control symptoms in Alzheimer, others are disease-modifier assets. So our dime pipeline is very rich, and we are very excited about it, actually.

And our next question today comes from Jason Gerberry with Bank of America.

So just for me on milvexian, can you remind us why you opted not to enrich in the SSP trial for antero sclerosis? And do you think that in any way poses a risk in terms of reading across from the positive efficacy results from the buyer data later today in SSP?

And then my second question is just as we look at the CELMoDs and the second line plus refractory multiple myeloma space, it's obviously getting increasingly complicated with recent data from the bispecifics. And so I'm just kind of curious how you guys are thinking about the relative positioning here if data are confirmatory on Phase III. Obviously, there's a lot to be kind of sussed out with your data, but do you see these as agents that maybe appeal more to community providers, more as like third, fourth line drugs? Or do you think they get used earlier? Just any color how you see it kind of positioning within an increasingly complicated space?

Well, let me start, and I'm going to ask Adam and then Cristian can chime in on your milvexian question. As we look at the CELMoDs program, generally, we're very excited about the data that we've already seen and about the commercial potential, particularly in light of some of the changes taking place in that landscape. But Adam, do you want to elaborate?

Yes. Jason, thanks for the question. Just building on Chris' comment. We've got good momentum coming off the [ ASH ] meeting last year, and we see excitement building around our overall CELMoDs portfolio, iberdomide, mezigdomide, and [indiscernible] in hematology. And this is a market, Jason, that we know very well. This is a competitive market. It's a fragmented market, but there remains a need for more effective and safe treatment options that can address the majority of patients. Particularly those that are treated in the community setting. And roughly 70% to 80% of patients are treated in the community.

Now while REV and PAM based combinations are the backbone of treatment across early lines of multi myeloma, there's an opportunity to improve upon their depth and durability there's an opportunity to improve on their tolerability. And we expect iberdomide will provide that balance of high potency, a manageable toxicity profile combined ability with anti-CD38 with the convenience of an oral treatment. And we continue to hear positive feedback from physicians.

So our goal is to make iberdomide foundational in myeloma, replacing images in earlier lines of treatment. So this is going to be for iberdomide, a second-line product largely used in the community in combination with [ daratumumab ].

Ultimately, longer term, we believe that these can serve as partners for TCEs and cell therapy. So we'll be studying that there. We presented data with Pfizer's TCE at [ ASH ]. So once approved, we expect good adoption over time in the community in second line as most patients just don't have access to cell therapies or bispecifics due to safety and accessibility challenges. So our teams are ready for the launch of iberdomide. We know the work that we need to do to establish both [indiscernible] in this competitive market, and we're excited to bring them to patients. Cristian?

So Jason, thank you. It's a very good technical question you're asking. But let me help you to clarify some of the eligibility criteria from the [ SOC ] study that Bayer is running and our [ ibrexa ] drug studies can be different. But when you look -- we didn't disclose our baseline patient and disease characteristics like they did. And in a few hours, we will say they also be the outcome. But I can tell you that the two studies are very similar in the patient population.

When you look at the events that are causing the stroke, you have three categories. large artery antero sclerosis. These are events that are coming faster. You have events coming from the [indiscernible] strokes. These are when we have the inclusion of small arteries in the brain. And then have trucks that are coming from embolic events that you don't know the source and unknown source. So this will not be very different between the two studies. And we believe that there is nothing -- and by the way, we control the number of events coming from [indiscernible] so we will not have a disproportion of that because it's capped in terms of events. So this gives us confidence that the two studies and the way we run our study at least, is the right way.

And our next question today comes from Evan Seigerman at BMO Capital Markets.

Mark Matan on for Evan. I wanted to ask two commercial questions real quick. So first on Opdualag in the fourth quarter. We saw in the U.S., particularly strong growth even relative to maybe prior years in 2024. Can you talk about some of the dynamics that may be contributing here obviously, the standard of care and melanoma, but are there particular physician engagement efforts that are contributing in the U.S?

And then secondarily, on Reblozyl, I know highly penetrated in MDS anemia, can you just help contextualize how much more room there is for growth in this indication?

Yes, thanks for the question. So Opdualag has become a standard of care in first-line metastatic melanoma in the United States. Opdualag is now approaching 4 years post launch and has over 30% market share. In fact, when you look at the totality of BMS market share in metastatic melanoma, we're now over 65%.

So our objective is to continue to expand our share. There's still roughly 15% of patients that continue on PD-1 monotherapy. And so there's an opportunity there to source that business this year. Additionally, we started to launch internationally in markets like Australia, U.K. and France that will contribute to growth in 2026. We also expect in all commerce indication in Europe in Q2, which will drive significant growth internationally. So we see opportunities to increase sales of Opdualag in the U.S. and as well as ex U.S. with a broader label.

As far as Reblozyl, as you mentioned, Reblozyl delivered continued strong growth. As you heard from both David and Chris. Reblozyl is now annualizing over $2 billion of sales worldwide, we're continuing to drive demand across first-line RS positive and first-line RS-negative patients.

We expect to see continued strong growth, particularly in the RS-negative patients where there's an opportunity for growth. We saw a very rapid uptake initially post command in RS-positive and RS-negative provides the greatest opportunity for growth in the United States. And outside of the U.S., in many markets, we're just starting to launch and get reimbursed in first line. So overall, we see continued solid growth for Reblozyl in first line this year, and we expect strong performance.

Thanks, Adam. And operator, we'll have one more question, then Chris will make a brief closing.

And our final question from Stephen Scala with TD Cowen.

Apologies, this is an Eliquis question. But I don't think this product has grown double digit in several years, but then will in 2026. And it's still not absolutely clear why there will be a step down in '27 if the 2026 is boosted by higher commercial price, why won't that also boost 2027. I understand about OUS patent expirations, but OUS in its totality, is only $4 billion, and I think some patents have been off for years. I would -- I think it's striking for a product to go from double digit in 1 year to $1 billion decline in the following. So it seems like what you're really saying is U.S. prices coming down in 272 and it's not clear why. And related to this, how did the contributing $7 billion of Eliquis API to the U.S. government impact the P&L?

Great, Steve. Thanks for the question. Just at a higher level. Number one, we continue to see strong demand performance with Eliquis, and that's going to continue in '26. When you look at the price reduction that took place in the United States, that will eliminate the inflationary healthy CPI penalties of the rebates this year and into next year.

When we look at in totality, you're right, roughly 70% of the Eliquis business is in the U.S. This is a very large brand. And so we expect in November of this year that we will lose exclusivity in Europe, and we would expect rapid and steep decline like we have seen with other small molecules outside of the U.S. that's why we would expect to see that step down in 2027.

And just on your question on the strategic reserve, that's not a material impact on the overall business, just given the magnitude of the business as well as just the amount of product that will be provided in that reserve. So no impact there. So thanks for the questions. And maybe just in conclusion, we have spent, as we've discussed on these calls for the last number of quarters, significant time on execution as a company across functions.

I think what you see in the numbers we put up today is that we're doing what we said we would do. We've become much more focused. We strengthened execution across all of the relevant functions in the organization. We've built a growth portfolio that has very strong momentum coming into the year. We have a pipeline as has been discussed on this call, differentiated assets that is now within months of meaningful data readouts.

And finally, we've continued to strengthen the company financially. And that, of course, gives us strategic flexibility to not only return capital to shareholders, but continue to add substrate for growth. I'm incredibly proud of the strong foundation we have coming into this year, which we couldn't have contributed to without the commitment and dedication of my colleagues at BMS.

So thank you all for joining us today. As always, the team is going to be available for any follow-ups, and have a great rest of the day.

Thank you. That concludes today's conference call. We thank you all for attending today's presentation. You may now disconnect your lines, and have a wonderful day.

Good morning, everybody. I'm Chris Schott from JPMorgan and welcome to the 44th Annual JPMorgan Healthcare Conference. It's great to see everybody today.

So it's my pleasure to be again -- to be introducing Bristol-Myers to again kick off the conference this year. From the company, we have Chairman and CEO, Chris Boerner. Chris is going to do a quick presentation and then we're going to go to a fireside format from there. So with that, we'll turn it over to Chris. Happy New Year and looking forward to the presentation. Thanks, Chris.

Thank you, Chris, for the introduction, and it is fantastic to be back kicking off another JPMorgan Healthcare Conference. Obviously, we're going to be making some forward-looking statements today, so these are my disclosures.

Let me start with just a reminder of our overarching goal as a company. We remain focused on building a company that's strong financially and has the substrate to deliver industry-leading sustainable growth heading into the 2030s and beyond. Before discussing 2026 and the road ahead, let me start by quickly highlighting the progress we made against that goal last year. 2025 was a year that was focused on execution. And we have made meaningful progress across a number of different fronts. Our growth portfolio increased 17% in the first 9 months of the year. And remember, this is a portfolio that is designed to be comprised of multiple differentiated products that are earlier in their life cycle, so they have a long runway ahead of them.

And as a result, our future growth will not be dependent upon 1 or 2 blockbuster products. In fact, we now have 4 products from that portfolio that are annualizing with sales of over $1 billion each and that includes Opdualag in melanoma, Breyanzi, our CAR-T therapy in lymphoma, Camzyos, the first-in-class treatment for obstructive HCM and Reblozyl, which is actually annualizing to over $2 billion in sales. And each of these products continues to be a core element of how we're going to grow the company and each has good momentum coming into this year. Beyond commercial performance, we made important pipeline progress last year and I'm going to speak to a subset of that pipeline in a moment. We augmented that pipeline last year with strategic business development, completing 5 deals, all designed to meaningfully add to the long-term growth profile of the company and we remain highly disciplined in the process.

Our strategic flexibility to do business development was enabled by continued financial discipline. We are well on our way to delivering on the $2 billion cost optimization that we announced roughly this time last year. And that progress includes a full-court press to rewire how we operate as a company and to make full use of technology, including AI across the enterprise. As a result of all of these efforts, we exit 2025 as a much stronger company. We have a strong balance sheet. We've reduced our debt obligation, thanks to achieving our $10 billion debt pay down ahead of schedule. We have very strong cash flow because of the commercial performance we've had. And we had good momentum across the business and we anticipate that momentum carrying into this year.

Speaking of this year, it's going to be a very busy year across multiple fronts, notably with respect to the breadth and depth of our pipeline. Let me highlight a few late-stage assets across all of our therapeutic areas with anticipated readouts this year that we believe has the potential to deliver significant value to patients and to the company. And let's start with neuroscience. Cobenfy was approved just over a year ago as the first new mechanism of action for the treatment of schizophrenia in decades. Beyond schizophrenia, we have a broad development program underway. In Alzheimer's disease psychosis, we expect readouts from our pivotal ADEPT-1, 2 and 4 studies later this year. And I think as many of you know, this is a devastating condition with upwards of 40% of Alzheimer's patients experiencing psychosis symptoms with really no great treatment options available today. We're also pursuing programs in Alzheimer's agitation and cognition, Bipolar I Disorder and Autism Irritability. Each of these represents a multibillion-dollar opportunity.

In cardiovascular disease, milvexian is our Factor XIa inhibitor that has the potential to redefine anticoagulation therapy for thrombotic disease. In fact, milvexan is uniquely positioned to be the only Factor XIa -- oral Factor XIa for atrial fibrillation. And potentially the -- a best-in-class treatment in secondary stroke prevention where anticoagulants are not approved today. We expect to share Phase III results for both of these indications in the second half of this year. In immunology, admilparant has the potential to redefine the standard of care in pulmonary fibrosis as a differentiated treatment for IPF and PPF. The lead program in IPF is progressing well and we expect to share Phase III results this year. And we expect PPF data to follow shortly thereafter in early 2027.

In oncology, we're developing pumitamig, our PD-L1 VEGF bispecific with our partner, BioNTech. This is a space, obviously, we know very well, and we believe pumitamig can redefine the standard of care across multiple tumor types. Our strategy with this asset is to be either first or second in each of the indications that we're pursuing. By the end of this year, we expect to add 3 new registrational trials, including a broader reach across 2 non-small cell lung indications and a study in head and neck cancer. We are also moving forward with earlier-stage novel combinations, including with ADCs, for example, our ADC iza-bren in collaboration with SystImmune, with other I-O therapies such as BioNTech's mRNA cancer immunotherapy and with novel targeted therapies, including a study with our PRMT5 inhibitor.

In hematology, iberdomide and mezigdomide are 2 oral CELMoDs in multiple myeloma. Based on the data we have seen so far, we are increasingly confident of the potential for both of these products to become a standard of care. Iberdomide has already shown a significant improvement in MRD negativity rates and we expect PFS data later this year. We also expect to see the first Phase III readout for mezigdomide later this year. And what we really like about both of these assets and in fact, this platform generally is the potential for these degraders to be combined with standard of care as well as with newer treatments like CAR-T and T-cell engineered antibodies. Each of the programs on this slide targets large, underserved patient populations. These products are novel and differentiated from existing and future competitor products. And as a result, we believe they all have the potential to deliver multibillion-dollar peak sales. Collectively, they represent a critical leg of the stool of how we strengthen the long-term trajectory of the company.

And while we'll see data with each of these programs this year, these assets are part of a much larger catalyst pool that gives us multiple shots on goal across new molecules, life cycle management opportunities and key early-stage programs. The breadth and depth of these opportunities is illustrated on this slide. In 2026 alone, we expect registrational data for 6 potential new products, milvexian, admilparant, iberdomide, mezigdomide, arlo-cel and RYZ101, as well as meaningful pivotal line extension readouts for SOTYKTU and Cobenfy. Most of these readouts will occur in the back half of this year. Importantly, while the science needs to play out here, based on the totality of the data that we have seen so far across these programs, we are very eager to see these readouts and we'll keep you updated on the progress. And of course, keep in mind, we have more key data readouts coming beyond 2026, the totality of which portends a wave of launch opportunities that will take place between now and the end of this decade as vividly illustrated on this slide.

This is a data-rich period where we have the potential for more than 10 new medicines and over 30 meaningful launch opportunities by 2030. These launches add additional growth drivers to the impressive performance that we've already seen in our existing portfolio and which I referenced earlier. And they expand our commercial presence in each of our core therapeutic areas. Taken together, what emerges is a younger and more diversified portfolio that will provide an impressive foundation for sustained growth leading into 2030 and beyond, which, as I noted earlier, remains our guiding objective. Now we have to deliver on that promise, and that means ensuring that we have an R&D organization that not only is adept at identifying promising areas of science but also consistently execute in a way that translates that science into new medicines with the highest probability of success.

To that end, Cristian Massacesi, joined us last year as our Chief Medical Officer and Head of Development. Cristian and his team are evolving our approach to development to exquisitely focus on 3 areas: great science, execution and value. On science, we're going to continue to prioritize exciting areas that we know well with a focus on building depth in each of our core therapeutic areas. With respect to execution, we've taken steps to increase the probability of success, applying more rigor to the design and execution of all of our clinical trials. We're also using AI and machine learning to power our R&D engine and bring treatments to patients faster. And finally, on value. We continue to be very disciplined in prioritizing programs where the science is highly differentiated and there is significant commercial value. You've seen that on display recently and how we've evolved our portfolio and you can expect that focus to continue.

Over the last 3 years, we focused on making execution stronger across the entire organization. Ultimately, our goal here is to ensure that we're investing our resources in the best science, enabling us to bring important medicines to the market with the highest probability of success and delivering ultimately more value to patients, to BMS and to our shareholders. While we have more work to do, I'm very proud of the progress that we have made so far. We have strong financial flexibility, which drives strategic flexibility, enabling us to invest in our business and deliver value to shareholders. In fact, we have returned over $22 billion to shareholders over the last 3 years, and we've increased our dividend 17 consecutive years. Further, we continue to bring exciting science into the company through business development. We did over the past 24 months, completing $30 billion of deals, including 5 deals in 2025 that I referenced earlier.

So in conclusion, we're doing what we said we would do. We've strengthened our execution across the entire company. We've built momentum into our growth portfolio and we expect that to continue into this year. We've prosecuted a pipeline of differentiated assets. That pipeline is now within months of a barrage of meaningful catalysts that kick off a wave of potential new product launches and approvals between now and the end of the decade. And finally, we've strengthened the company financially, injecting strategic flexibility that enable multiple paths to value creation going forward. I'm incredibly proud of the foundation we've strengthened coming into this year, which wouldn't have been possible were it not for the commitment and dedication of my colleagues at BMS. We like the setup that we have for 2026 and I very much look forward to keeping you updated on our progress.

And with that, Chris, I will turn it over to you for questions. Thank you.

Great. Well, appreciate those remarks. Maybe just open up the conversation. I guess you're about 2 years into the CEO role now. So maybe just talk a little bit about in that -- in those 2 years, what's gone better than expected? What are areas where you still think the company needs to make improvement? And just kind of as you turn the page to 2026, what are you most focused on in your role?

Well, what I would say in aggregate is that when you look across all of the puts and takes, I feel very good about where we are as a company and I'm confident on executing against the plan and ultimately achieving the objective I just talked about. In terms of things that have gone better, look, I think that I highlighted the growth portfolio. We're seeing very good progress in that portfolio through the first 9 months of last year, double-digit 17% growth. We'll talk more about how we ended the year in a few weeks. But that portfolio is performing very well. It's got good momentum across a number of key products. And of course, that provides a nice foundation for how we think about growing this company in the back half of the decade and beyond. So I feel very good about where we are there.

I highlighted just before that we're making very good progress in terms of taking costs out of the system. We're well on our way to delivering on the $2 billion that we announced last year. We had $1.5 billion of taking costs out that we announced in 2024. But more important than just the numbers is that we built this muscle around being very financially disciplined, making sure that we're spending our resources in the right place and whether we're dropping that -- those cost savings to the bottom line or reinvesting in the business, that financial flexibility is super important for a company like ours because it gives us strategic flexibility. So I feel great about that.

And third, I also feel very good about the early-stage pipeline, which we don't talk a lot about. But if you look across some of the assets that are going to become increasingly important, particularly as these Phase IIIs play out, we've got an exciting program with CD19 NEX-T. The data there in autoimmune disease looks fantastic. We've got additional CELMoDs, whether it's our prostate cancer CELMoD AR LDD or golcadomide in lymphoma, which might very well be a sleeper because the data there looks quite impressive as well.

So that early-stage program continues to progress, which I'm quite happy about. Obviously, the things that haven't gone well, we had some setbacks on the development side in 2025. But you bring in the right team, you focus and double down on execution. That's what Cristian and his team have done. I feel good about the progress we've made there. And that's part of just an overall focus that we have around execution, which I would say wraps around all of what I just described. So net-net, I feel good about where we are. And our priorities for 2026, not surprisingly, are the same, continue to drive commercial execution, continue to prosecute that pipeline, maintain financial discipline that gives us the strategic flexibility to continue to bring great science into the company. If we execute, I feel good about where we are.

Great. Maybe just building on that, I think in this discussion last year, I asked you how confident you were about Bristol's ability to manage through the patent expirations that are coming up. I guess just how has that view changed as you've gone through 2025? You mentioned some products moved forward and there were some setbacks. But just your level of confidence right now and as we think about those next 5 or 6 years of LOEs.

Well, my confidence is still very high. And I would say incrementally, it's higher than where we were last year and a lot higher than where we were when we go back 2 or 3 years ago. And the reason for that is, we now have really good confidence and we can see the trajectory of our existing product portfolio and that's growing quite nicely. And while Eliquis is not part of that growth portfolio, Eliquis continues to perform very well. And that gives us a lot of confidence that, that business is going to continue to grow. It's got good momentum coming into this year. So that's a big piece of the confidence that I've got. And then I would say, in spite of the setbacks that we had, look, we've got a great team in the development organization. Cristian has brought in new energy and focus. So that's really good.

And if you look at the sheer number of opportunities that we have, I highlighted the opportunity for 6 new medicine pivotal data this year alone. And if you just expand the aperture just a bit, you have the opportunity for upwards of 10 new medicines between now and the end of the decade with over 30 meaningful life cycle management opportunities. There's just a lot of shots on goal there and you don't have to wait very long to see how that's going to play out because you've got a very large swath of those pivotal studies that are going to start reading out in the middle of the year. So that gives me a lot of confidence. And I can't tell you how important it is to be financially in the place that we are, to be very disciplined in how we've operated, to have great cash flow. Our balance sheet looks good. We've drawn down our debt. And that really puts us in a strong position as a company and that gives us optionality.

Just, I guess, on that pipeline front, I mean, it is a big year coming in, '26. You laid out all those assets reporting out. What is, I guess, a good enough outcome look like for you? You've laid out some kind of growth objectives as you kind of exit the LOE cycle. Just elaborate a little bit more about what has to work here to support those growth objectives? And maybe where is your highest level of confidence of these assets reporting out?

Well, the good news is that we've intentionally built this portfolio to be diversified, broad and replete with assets that individually have significant commercial potential. And I say that because in some ways, what that implies, to sort of reframe it is, we don't need everything to work. We have a lot of confidence in the programs that are going to be reading out starting this year. But this is a highly diversified set of assets that we feel good about each of the chances individually but we're not beholden to all of these programs working. So that's an important point right upfront.

What I would say about the swath of assets that are coming forward is, if you look at the clinical and scientific rationale just behind the 6 new product potential data readouts that we have this year, milvexian, we've got very good Phase II data across both of those indications, SSP and AFib. We've seen competitor data for SSP, their Phase III. So that gives us a lot of confidence in the program and we think we have a better asset. We've got a lot of rationale behind Cobenfy and we can talk more about that. Admilparant, 2 very strong Phase II datas in terms of efficacy leading into the IPF and PPF program. So you kind of go down the list, you have a lot of confidence in these programs. And I think that, obviously, we need to see the science play out here but it gives me a lot of confidence these programs are going to be an important catalyst and second leg of the stool, if you will, for the growth of the company.

There's a couple of other bigger picture one. Maybe before we go into the individual assets, BD priorities, I mean you talked about financial flexibility. Where are you most focused at this point from a BD perspective?

Well, business development remains a top priority for how we think about capital allocation. We're going to cast a broad net but that net really is focused on how can we improve the growth profile of the company and deliver on that objective I talked about earlier. What that means practically is, obviously, we're going to focus on areas we know well. We've got opportunities to build depth across each of our core therapeutic areas. While we will look at opportunities across Phase I, II and III to the extent that we can index on opportunities that give us near-term growth, that's going to be important. But we're going to continue to be very financially disciplined in how we go about that. So we're going to look for ways that we can say we're the rightful owners of these assets. It makes scientific sense for us to be a participant. And ultimately, we've got to be able to stand in front of investors and you and others and say, this is going to add value to the company. But if those criteria are met, we've got the financial capital to be part of the process.

So it sounds like BD may be pivoting a little bit later stage just given the financials of the company.

I mean we're still building for the long term. So we see really attractive Phase II opportunities. For example, we're going to be -- and it makes sense for us to be the owners, we'll be in the mix.

And in terms of therapeutic areas, should we think about building on where the company currently has presence? Or could we be looking at more Karuna like deals where you're kind of adding adjacent vertical or a new vertical?

I think our primary focus is going to be to continue to build depth in the core therapeutic areas that we're in and we think we've got opportunities to do that really across each of those TAs.

Okay. Great. Maybe just shifting to the pipeline. You mentioned R&D organization, you've made some changes. Can you just elaborate a little bit more in terms of what's changed here? And when can we start to see some of the outcome of those changes being implemented?

Well, look, I think I would position everything that we've done in the context of R&D with what we've done in the broader organization. We have been fixated on ensuring that we're driving execution across the entire company. We have something internally we call our say-to-do ratio. When we say we're going to do something, investors should have confidence that we're going to deliver on it more often than not. And that's become a mantra for the company across the board. And obviously, when you see that you have issues that pop up, you got to move quickly to address them. We've done that in the context of development. Cristian has brought in a new energy and perspective there. And I think, again, the focus is on making sure we're focusing on the right areas of science, that we're focused on areas that we know well and we can add value to, building depth in each of those TAs.

Execution is super important. So we've taken a hard look across all of our clinical programs, making sure that we're doing everything we can to deliver those programs not only on time but with the highest probability of success. Those efforts are well underway and we're seeing the benefit of those already. And then finally, taking a hard look at the portfolio to ensure that everything that we're investing in not only has clear scientific rationale but can deliver commercial value. We started that effort back in 2024. And I think any time we talk internally about research and development, right next to that is portfolio prioritization, which we're going to continue to be focused on. And again, you saw us externalize some assets in 2025. And we're going to continue to sort of leverage that portfolio effort to understand where we need to be making more investments, where we need to be looking for business development. And obviously, when appropriate, when there are things we should stop investing in.

Great. Going into individual products, maybe first starting on milvexian. We got secondary stroke and AF coming this year. Just maybe to start with how meaningful of a product could this be for Bristol, maybe specifically on that AF indication if it were to hit. Can you just talk about what you need to see with the profile and what is the opportunity set for the drug in that situation?

Well, I think if you look at the components of both of the milvexian programs, they have everything you look for in terms of becoming a very meaningful asset. First, there's unmet need across both SSP and AFib. And with AFib specifically, while products like Eliquis have been incredibly successful and the Factor Xas have made a significant difference in AFib, it's helpful to remember, 40% of patients either aren't treated with a Factor Xa or they're undertreated because of a concern of bleed. So there's clearly an opportunity to layer on top of standard of care for those patients. Second, you've got really strong clinical rationale for the development of milvexian in both of those indications. We've got Phase II data for SSP. We have a very attractive Phase II program that read out positively in total knee replacement, which I think gives us an indication of how it will perform in AFib.

And remember, in spite of a competitor program failing fairly early, this program continued to enroll and enrolled quickly. We think we did the right study and there's been a lot of excitement amongst KOLs in enrolling those patients. So we feel good about the clinical rationale. And then while SSP is a smaller disease area, these are big commercial opportunities, about just shy of 1 million patients with risk of secondary stroke and 17 million patients with AFib. So that's really big, even if you just consider the 40% that are under or not treated with Factor Xa. So add those things up, this is going to be a potentially quite significant opportunity for us.

Maybe turning to Cobenfy. Can you just walk us through some of the recent trial amendments we saw with the ADEPT-2 study in Alzheimer's psychosis? Basically how much clarity does Bristol have at this point in terms of the profile of Cobenfy that -- from -- in that study?

Well, remember, when you talk about Cobenfy, it's important to recognize that we've got a broad development program. I highlighted a number of the programs that are going on. We've got Alzheimer's disease psychosis. I'll dive into that in a second. But we've got Alzheimer's agitation and cognition, bipolar and autism. So this is a broad program that we're developing. With respect to ADP, 3 studies this year. We actually have 4 studies on ADP. We've got 1, 2 and 4 reading out this year. We actually have a fifth ADEPT study that's a bridging study that reads out a bit later. We believe we're going to need 2 of those studies in order to file and that's typical in the space.

With respect to ADEPT-2, look, I think what we've been very careful about with this program, is making sure that we remain blinded to the data, that we maintain the integrity of the study. We worked very closely with FDA and the DMC on everything that we've done. And what do we know? Well, first, we know the relapse rates are consistent with what our expectations were. We know the fact that the DMC, when they looked at the data unblinded, they recommended that we continue to enroll and enroll up to the original patient numbers. And so that's what we're doing. And we anticipate that the study is going to read out roughly in the same time frame that ADEPT-1 and ADEPT-4 would read out.

So it's going to be an important year for that program. And if you just step back one more step and look at the rationale for Cobenfy in this space, that we feel -- still feel really confident about. We've got internal data, whether it's that relapse rate that I referred to earlier, the lead-in to ADEPT-1, we've seen that data. And then, of course, we've got external data going back to the early Lilly data that provides proof of concept here. So add it all up, there's confidence but we've got to see the studies read out.

Great. Just to maybe also help frame out the opportunity for ADP as -- to the extent we get 2 ADP studies to work, like just compare and contrast how that might look relative to the schizophrenia indication you've been launching?

Well, this is obviously a big patient population. You have 6 million patients more or less with, diagnosed with Alzheimer's disease. We believe roughly 40% of those patients have psychosis symptoms defined by hallucinations or delusions. So it's a big patient population. There's significant unmet need. Most of those patients, if they're being treated, they're being treated with D2s. Those D2s don't work particularly well and have the added problem that there's a black box warning for mortality in the elderly, clearly not something you want to see in Alzheimer's. And so if the profile that we believe exists here pans out, this is a significant opportunity and there's going to be excitement about it. And of course, then the focus will be on continuing to go and identify those patients and then build breadth and depth. And so I think if the study is positive, there's significant opportunity here.

And would this be only, think about a gradual ramp with it? Or could this be a little...

I think so. I mean I think this is generally a space where physicians are relatively conservative and I think with good data, it's -- there's a lot of blocking and tackling as we're seeing in the schizophrenia space in terms of getting physicians to try a product. But with the right profile, once they try it, they build depth pretty quickly.

And speaking of schizophrenia, talk a little bit about progress you've made there and kind of key priorities for that indication.

We feel very good about where we are with schizophrenia. And as I think we've discussed previously, this has all of the core components of a very big product. It's got very good clinical data. Once physicians try the product and see the benefit for themselves and more importantly, hear what comes back from patients, again, it's one where they start to build depth pretty quickly. The trick is, it's a conservative physician group. And so you've got to make sure that you're able to get them to do that first try. But there's no impediment to the commercial uptake of this product. So access is very good. The profile is panning out exactly as we thought. We're going to have data coming into the market this year that will help on dosing and switch.

So we think that data is going to be important to continue to accelerate the launch. We doubled the size of our commercial sales force to increase the shots on goal that we have in terms of talking to physicians about the efficacy profile. So you add it all up, I think you're going to continue to see a nice steady uptake with this product. And again, what you don't want to see are concerns coming forward that the profile isn't what you expected. And that's not the case here. When physicians and patients see the benefit of this product, they want to not only use the product but patients want to stay on the product and that's super important.

And sounds like steady is the way to think of this versus...

Steady is the way to think about it.

Perfect. Pivoting over to oncology. The CELMoDs, seems like this one could be a bit of a sleeper, less focused on by the Street and you've got a lot of confidence. Can you just help frame out the opportunity for those assets as we start to think towards the data this year?

Yes. I think you've characterized it well. Look, I was in the field talking to physicians about the opportunity that we have with iber and mezi. There's a lot of excitement about it. Remember, multiple myeloma, it's obviously a crowded space but patients cycle through lines of therapy and products relatively quickly. And many, if not most, of these patients continue to be treated in the community setting where the opportunity to have an oral therapy that combines well with standard of care is a really attractive proposition. And what's nice about what we're seeing with the evolution of this program is, leading into the Phase IIIs, we saw very good Phase II data. We now have the MRD negativity data for iber, which looks very, very good. And that portends success and an attractive profile when we see the PFS data, which will happen this year.

And then we've got the first of the Phase IIIs with mezigdomide this year. And this is a broad program. They're combinable assets. So again, it's one where when we see the data continue to evolve this year for both of those programs, I think if they play out the way we anticipate they will, these are going to be exciting opportunities. And I think we have a real opportunity to play in multiple spaces within multiple myeloma and help a lot of patients.

When I think about the CAR-Ts and bispecifics in the setting coming in, does that complicate how these drugs will find the kind of role in the market just given the standard of care is changing so quickly?

Well, I think the standard of care is changing very quickly. But I think that it's a complicated space. But as I referenced before, what we like about CELMoDs generally is, they're combinable. So you can combine them not only with standard of care monoclonal antibodies, for example but you can combine them with cell therapy. You can combine them with T-cell engineered antibodies. And so while it's a complicated space, in some ways, that plays nicely to the CELMoD program and in particular, what we're seeing with iber and mezi. So look, I was pleasantly surprised to see the level of enthusiasm to see this data precisely because I think it provides another bullet in the armamentarium that physicians have to treat these patients. It's combinable. The data looks pretty good that we're seeing. And now, of course, we've got to continue to see the data play out. Good news is, here again, you don't have to wait very long. You're going to start to see more data on both of these programs this year into next year and the following year.

Okay. And maybe one last one on the oncology front. The PD-1 VEGF, very exciting space. How do you think about Bristol differentiating within the category? It seems like there's a number of other players. It seems like every day another one kind of coming into the space, I know you're one of the earlier ones. But how do you think about kind of uniqueness of the asset and the clinical program you're running?

Well, we've obviously seen not only data with the asset that we're working on with BioNTech but also you continue to see an evolution of the data in the space. And I will tell you, we continue to be attracted to the data that we're seeing. This is data that has really good activity in very difficult-to-treat patients. So our conviction that this could be a new platform therapy, I-O therapy continues to be very strong. So differentiator #1. We like the data that we're seeing in general and we like the data that we're seeing with this asset specifically.

Differentiator #2, this is a space we obviously know very well. I've gotten to know the team at BioNTech quite a bit over the last year plus. And what I would say is that you combine the scientific expertise that they have, not only with this product but also with their broader suite of oncology assets, along with the incredibly deep experience that we have in the I-O space, you put those 2 teams together and have a partnership that we've built over the last year, which is very, very strong. I think that's differentiator #2.

Differentiator #3 is, we think we are in a prime position to be first or second in each of the disease areas that we're targeting within oncology. And what do we know from our existing position in I-O is that being third, fourth or fifth is pretty challenging. And that's challenging today, never mind what it's going to look like when these products launch. So we really believe that being first or second is super important to driving value. And I think with the expertise that we have across the 2 companies, we're in a good position to do that. And if the science evolves, we're in a great spot with this partnership and this could be a meaningful opportunity.

Great. Last couple of minutes here. Maybe talk about 2026. I know you haven't formally given guidance but just kind of pushes and pulls we should all be considering as we think about the year ahead.

Yes. We'll obviously provide more details about 2026 in a few weeks. But what I would say just generally, objective remains the same. Our focus is on continuing to build a strong company, a strong company that's very financially disciplined and a company that continues to be focused on how do we put all of the pieces into a place to be a company that can deliver sustained long-term growth exiting the decade into the next. How do we do that? Commercial execution and delivering on our financial commitments, priority #1. We've got good momentum with that growth portfolio coming into this year. So I feel good about that. But that -- executing on that is super important.

Second, obviously, with the wealth of assets we have coming in the pipeline, we got to deliver on those. So there's a lot of focus that we have in the company on good, solid blocking and tackling execution on the development side, more generally across R&D. So that's the second thing. Third, we've got to continue to be smart about how we allocate our capital. So we've talked about business development. That continues to be a priority for us and being smart about the opportunities that we choose to invest in. I think that's going to be important and that's a priority.

And last but not least, I'm very proud of the changes that we've made in the organization with respect to being much more focused on execution, being much more disciplined in how we operate, rewiring to be more efficient. That includes continuing to invest in technology. And given the opportunity we have, given this moment in time at the company, we're going to continue to push hard on that and that's going to be a focus area as well.

Great. One last one for me. MFN tariffs, I know Bristol recently did a deal with the administration. Just your perspective on what that means for the company and maybe for the industry more broadly, that agreement?

Well, we signed the deal. The nice thing about our portfolio, remember, because we have relatively limited Medicaid exposure, so you guys can do the math in terms of how you think about the impact of that. What I'm really excited about is that we now have the ability to start focusing -- we talked about this earlier, on value creation and hopefully begin thinking about partnering not only with this administration but thinking about this more globally on -- in the U.S., how do we continue to simplify the ecosystem in the United States? Because if ultimately, you want to increase access, increase affordability, you've got to take costs out of the system. And the way you do that is make this a simpler environment within which to operate. And there, I think the administration has been quite supportive in terms of finding ways to sort of circumvent third parties and middlemen. So we're going to continue to focus on that.

And then I would say a second area where the administration has been pretty helpful is in ensuring that countries outside of the United States pay their proper share for the innovation largely that's taking place here. So we'll continue to engage there. But I feel good that we've gotten beyond that deal and now we can start focusing more on fundamentals. And the great thing about where we are as a company, we have a lot of fundamentals to focus on. We've got good commercial execution and a lot coming in the pipeline. And I'd leave you with -- if there's one thing that we're going to be focused on, is ensuring that we deliver that swath of new opportunities because there's a lot coming.

Great. Well, appreciate the time and exciting year ahead. So thanks for the comments.

Thanks. Happy to be here.

Welcome to the Bristol-Myers Squibb Hematology Drug Development Update Conference Call. [Operator Instructions] Please note this event is being recorded. I would now like to turn the conference over to Kate Bender, Investor Relations. Please go ahead.

Good morning. This is Kate Bender from Bristol-Myers Squibb, Investor Relations. And I'd like to thank you for joining us today to discuss our progress across key programs that are expected to shape the future of hematology treatments. It's exciting news for patients and the company, and we have a lot to talk about.

I'm joined by Cristian Massacesi, our Chief Medical Officer and Head of Global Drug Development, who will take you through our slide presentation. Following the presentation, 3 of our leaders will join Christian for Q&A. Lynelle Hoch, President of our Cell Therapy Organization; Monica Shaw, Senior Vice President of Oncology Commercialization; and Rosanna Ricafort , Vice President of Hematology and Cell Therapy Global Drug Development.

On Slide 2, please note that 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 our SEC filings and we specifically disclaim any obligation to update forward-looking statements even if our estimates change.

And with that, I'll hand it over to Christian to begin our presentation.

Thank you, Kate. Good morning, everyone. It's great to be here with you in my new role at BMS. I was drawn to the company because of the strong science, broad portfolio and innovative pipeline across high-growth therapeutic areas. In the 4 months since I joined the company, I'm also been impressed by all the people I have met and their dedication to our mission to discover, to develop and to deliver innovative and life-changing medicines to patients.

Turning to this agenda on Slide 4. The purpose of bringing you here for this event is to share our strategic approach to drug development with an emphasis on our hematology therapeutic area. We are excited to highlight the strength and innovation of our research platforms, which are driving advances across targeted protein degradation and cell therapy. Today, I will highlight and contextualize some of our newest data presentations from the International Myeloma Society and ASH congresses as well as touch upon some early-stage assets to watch. This data not only showcase the progress of our assets, but also reinforce our confidence as we look forward to many pivotal readouts next year. Our goal is to provide you with a clear understanding of how these developments reinforce our leadership position in hematology and why they represent significant opportunities for Bristol's future growth.

Moving to Slide 5. Success in our global drug development organization is grounded in 3 key priorities: science, execution and value. Everything we do is rooted in science. We are leveraging our deep scientific expertise to develop assets that we believe can provide a clinically meaningful benefit and set new standards of care. Our approach to science and pipeline is dynamic. We assess each of our opportunities on an ongoing basis to ensure we are allocating our time, people and capital behind the most promising growth opportunities.

At the same time, we are laser-focused on achieving best-in-class execution. We are operating with urgency and precision across the entire development organization and execution is not only delivering clinical trials, but also being highly disciplined to ensure each study has the highest probability success. In this process, we are also utilizing AI and machine learning to power our R&D engine and bring treatments to patients faster.

Our third key priority is value. We are developing medicines that address high unmet needs, creating value for patients by providing innovative treatments with the goal of improving upon current standards of care and striving for cure, while at the same time, delivering value to Bristol-Myers Squibb and our shareholders. We are being more deliberate in how we prioritize programs. Pursuing assets where the science is highly differentiated and where we believe we have the ability to create value. These priorities and portfolio discipline in what we pursue and where we allocate our resources are applied across all therapeutic areas. Ultimately, the goal of this strategy is to ensure that we are investing in the best science with the highest probability of success so that we can deliver more value to all of our stakeholders.

On Slide 6, it's important to highlight BMS strong legacy and decades of experience in hematology, which is a true differentiator. We have been at the forefront of this area for decades with a rich portfolio and pipeline of truly transformative treatments across hematological diseases. More recently, BMS is proud to be the first and only company with 2 approved CAR-T cell therapies in 2 distinct disease areas with Abecma and Breyanzi. Reflecting on where we are today, we have the first and only CELMoDs in late-stage development with 6 ongoing Phase III studies, bolstering our leadership in targeted protein degradation as well as Arlo-cel, the first GPRC5D targeting CAR-T assessed in pivotal trials which expands our leadership position in cell therapy.

Last week, we announced Breyanzi's approval as the first and only cell therapy marginal zone lymphoma. Marking its approval across 5 cancer types, more than any other CD19-directed CAR-T. Looking ahead, we will continue to advance scientific discovery and maximize our late-stage portfolio value by investing in these platforms that have the potential to transform the treatment paradigm for hematological diseases and further extends the BMS leadership.

On Slide 7, you can see our next chapter in hematology is driven by 2 complementary platforms, targeted protein degradation and cell therapy. Starting with target protein degradation. We are building on our legacy with a new wave of innovative science across therapeutic areas with multiple assets in development. Our researchers are leveraging 3 different modalities for targeted protein degraders. CELMoDs, ligand-directed degraders and degrader antibody conjugates. This 3-pronged approach allows us to match the right modality to a mechanism of action to target what have previously been considered undruggable targets. One of the most exciting qualities of these assets is that they are highly combinable with other approaches. Such as targeted therapies, immune modulators, CAR-T cell therapies and also complex biologics.

Turning to cell therapy. This is an area where we are a proven industry leader with 2 approved CAR-Ts into distinct targets. Breyanzi across the broadest array of B-cell malignancies and Abecma the first approved CAR-T multiple myeloma. While we are focused on delivering the first and best-in-class treatments across blood cancers, we are also exploring opportunities to increase accessibility of cell therapy for more patients. The focus of today's event is on hematology. But let's not forget that both of these platforms will enable our leadership across multiple therapeutic areas, including solid tumors and autoimmune diseases. Taken together, our deep knowledge in targeted protein degradation and proven track record in cell therapy execution gives us multiple shots on goal to deliver the next wave of hematology assets.

Turning to Slide 8. We have a broad hematology portfolio and pipeline, diversified across various diseases. Including multiple myeloma, leukemias, lymphomas and anemia. We have critical assets spanning both late and early stages. So we strongly believe our diverse hematology pipeline is differentiated and positioned to contribute meaningfully to our growth in the years ahead. While I would love to speak in detail on each of our assets. Today, we'll be focusing on a subset of assets you see start here where we expect to have key data readouts in the next 12 to 24 months. Let's transition now beginning with multiple myeloma, where I will walk you through our vision, recent data and portfolio.

On Slide 11, you see our exciting next wave of assets in multiple myeloma that I will be covering today. We are well positioned to leverage our research platforms with 2 pivotal stage CELMoDs iberdomide and mezigdomide in our next generation of first-in-class CAR-T assets, arlo-cel and our BCMAxGPRC5D dual targeting CAR-T.

Moving to Slide 12. Our vision for iberdomide and mezigdomide is to become the first novel CELMoD protein degraders approved in multiple myeloma. These agents are well positioned to be essential foundations across the multiple myeloma treatment landscape based on their enhanced potency and immune stimulation. CELMoD's are combinable oral agents with the potential to displace the IMiDs, Revlimid and Pomalyst across patient segments and be the combination partner of choice for other T-cell redirecting therapies.

Turning to Slide 13. We know the IMiDs Revlimid and Pomalyst have been a cornerstone of multiple myeloma treatment for decades. But this disease remains incurable, with highly heterogeneous patients requiring novel and convenient therapies to optimize outcomes of other current standards of care. Iberdomide and mezigdomide are potent oral CELMoDs that evolved from the IMiDs. The CELMoDs are not just incremental improvements, they represents a potential new foundation for multiple myeloma treatment by inducing even greater and faster targeted protein degradation. Based on their pharmacological and clinical profiles, they each address distinct patient populations and combination regimens across 4 ongoing Phase III trials.

We envision iberdomide replacing Revlimid in newly diagnosed post-transplant maintenance. The head-to-head Phase III study of iberdomide versus Revlimid is ongoing, we did expect it in 2029. In early relapsed refractory patients, our intention is for iberdomide to be combined with daratumumab because iberdomide and anti-CD38 monoclonal antibodies have a synergistic activity. Our second CELMoD mezigdomide induces a maximal protein degradation, and we plan to use it in combination with proteasome inhibitors in patients who are anti-CD38 exposed or refractory. I will dive deeper into our CELMoDs data in the next slides.

Slide 14 shows the recent early phase data we presented at IMS Congress in September, for iberdomide in combination with daratumumab and dexamethasone. In this population of newly diagnosed patients not receiving stem cell transplant, this data set demonstrated deep and durable responses. Patients achieved an overall response rate of 95% with 68% of the patients achieving a complete response at 22 months. Additionally, we tested minimal residual disease, or MRD. MRD negativity is important as it correlates with PFS and OS and is an indicator of clinical benefit and improved outcomes. In this study, IberDd induced MRD negativity in over 2/3 of patients. These results are very encouraging. When you look at historical results for standard regimens in the MAIA and BENEFIT trials, less than 1/3 of the same population of patients achieved MRD negativity.

Turning to Slide 15. The iberdaradex regimen demonstrated a manageable safety profile consistent with prior data with no new safety signals observed. They were overall low rates of grade 3 or 4 non hematological events and hematologists are well accustomed to managing neutropenian infections in these patients.

In summary, iberdaradex is the regimen that we are currently studying in the ongoing pivotal EXCALIBER-RRMM study. In September, we announced that this study evaluating iberdomide in combination with standard therapies, daratumumab and dexamethasone demonstrated a significant improvement in MRD negativity rates in a second to third line multiple myeloma patient population. We expect to have the PFS data next year.

Let's switch focus to our second CELMoD with multiple myeloma, mezigdomide, on Slide 16. At AMS, we presented early phase pooled data for mezigdomide in combination with both proteosome inhibitors, bortezomib and carfilzomib plus dexamethasone across the population of retreated patients ranging from 1 to 4 prior lines of therapy, the combination of [ MEZ PI index ] demonstrated deep responses. Overall response rates were over 80% in patients who received 1 or 2 prior lines with responses above 70% in more heavily pretreated patients. Notably, in patients who had received 1 or 2 prior lines, complete response rates were over 25%. These results are encouraging as all of these patients had received prior lenalidomide with a subset of patients being refractory to PI or anti-CD38 agents. These results show that mezigdomide plus PI index provided benefit in patients regardless of the number of prior lines of therapy.

Turning to Slide 17. The safety profile for mezigdomide plus [ PI index ] regimen, showed Grade 3 or 4 adverse events were mostly hematological and were manageable with supportive care across these largely triple-class exposed population. These data support our ongoing pivotal trials for mezigdomide, SUCCESSOR-1 And SUCCESSOR-2, which are studying mezigdomide plus proteosome inhibitor in later relapsed multiple myeloma populations. We anticipate seeing the PFS top line data for both SUCCESSOR studies next year and look forward to sharing it with you.

Moving to Slide 18. I want to highlight the potential opportunities we see for novel combinations with CELMoDs in multiple myeloma, which extend beyond the regimens being investigated in ongoing pivotal studies. We have a broad research program combining CELMoDs with BCMA targeting bispecifics as well as exploring optimal sequencing of CELMoDs as pre-CAR-T conditioning agents or as maintenance therapy to enhance responses following CAR-T infusions. First disclosures of combination data for CELMoDs and the T-Cell engager [ elranatamab ] were just presented at ASH.

In the magnetism to re-study, we explored iberdomide plus era and in the [ MELT ] investigator-sponsored study, mezigdomide plus era. We have a compelling preclinical scientific rationale demonstrating synergistic activity of these agents. With CELMoDs potentially enhancing T-cell engager function. Early phase safety and efficacy data are encouraging. And studies are ongoing to optimize the CELMoDs and T-cell engager regimens in larger patient sets. Early data also suggests CELMoDs may play a role in optimal sequencing strategies with CAR-T therapies. The CELMoDs may enhance CAR-T cell expansion and subsequent potency when used as a preconditioning agents.

It may enhance CAR-T cell persistence when used as maintenance therapies, post CAR-T infusion. Exploration on novel CELMoDs approaches are ongoing in early phase studies and the data highlights the potential roles that CELMoDs may play to combine or enhance other growing modalities to drive better outcomes for multiple myeloma patients.

Moving to Slide 19. As pioneers in the field of cell therapy, we are committed to a future where more eligible patients with multiple myeloma are treated with the promise of CAR-T. Our vision is to offer patients a durable path towards a potential cure. While current therapeutic options have significantly advanced in recent years, there remains a need for new treatments to further improve outcomes. GPRC5D is a promising target for patients with multiple myeloma, both sequentially and in combination with BCMA. Our next-generation assets, Arlo-cel and the dual targeting BCMA and GPRC5D CAR-T, have the potential to address the unmet needs for these patients, with the hope of putting more patients on a path towards cure.

On Slide 20, you can see the latest Arlo-cel data we present at [ AMS ]. Arlo-cel, our GPRC5D targeting CAR-T is a potential first-in-class cell therapy for relapsed and refractory multiple myeloma. In this Phase I update, heavily pre-treated patients had received a median of 5 prior lines of therapy with nearly half receiving a prior BCMA targeting therapy. We recognize the post-BCMA setting is a growing segment with a high unmet need as more patients are receiving BCMA-targeted therapies earlier in their treatment journey. At the median follow-up time on nearly 2 years, Arlo-cel showed continued deep and durable responses with overall response rates of over 90% and achieved MRD negative complete responses in over 40% of patients. These efficacy results are highly encouraging in this difficult-to-treat late-line population.

Turning to safety results on Slide 21. Arlo-cel demonstrated a manageable tolerability profile. Rates of CRS, ICANS and on target of tumor adverse events were low grade and all resolved. There were no grade 3 or 4 events. Hematological adverse events were manageable and in line with what we have shown previously. In summary, following a onetime infusion of Arlo-cel, these safety and efficacy outcomes in a late-line population, including patients with prior BCMA exposure show a preliminary favorable benefit risk profile. This compelling data supported the ongoing pivotal Arlo-cel studies, QUINTESSENTIAL that is run in a heavily pretreated population, the data are expected next year and the QUINTESSENTIAL-2 the pivotal study in a BCMA population with data that are expected in 2028.

Turning to Slide 22. Our dual targeting BCMA and GPRC5D CAR-T is a potential first-in-class cell therapy in multiple myeloma. This asset capitalizes on the proven activity of these 2 clinically validated and independently expressed targets. We believe that targeting BCMA and GPRC5D simultaneously with a single infusion CAR-T maybe beneficial in preventing relapse that is driven by the loss of a single target. In taking a dual targeting approach, there is the potential to lead to a more durable important activity than what can be achieved with a single targeting approach. Phase I studies are ongoing in newly diagnosed and late-line patient populations. And we anticipate presenting the first clinical data for this asset next year.

On Slide 23, you see that our broad and diverse portfolio is well positioned to address the full continuum of multiple myeloma care from newly diagnosed patients to those with late-stage refractory disease. Our first and best-in-class agents, whether our novel onetime infusion cell therapy agents or our combinable or CELMoDs have the potential to offer new therapies for myeloma patients across treatment settings. We recognize that each patient is unique. And our commitment is to ensure that no patient segment is left behind. We look forward to sharing important data readouts beginning next year for these assets that will shape the future growth of the company.

Let's switch gears now. Moving on to discuss our exciting updates across our lymphoma assets. Turning to Slide 25. I'm excited to discuss 2 of our novel lymphoma assets from our targeted protein degradation platform. Golcadomide, our CELMoD which has 2 ongoing Phase III trials in LBCL and FL in our earlier-stage BCL6 targeting ligand direct degrader.

As highlighted on Slide 26, our protein degraders have the potential to disrupt the current standards of care across the [indiscernible] lymphoma. Providing patients with combination regimens that are chemo-free, all-oral or that can improve upon outcomes of the standard chemotherapy regimens offered today. Both golcadomide and our BCL6 degrader are first-in-class agents that we envision becoming therapeutic partners of choice for current or newly emerging therapies. Our goals for these assets are to improve upon the cure rates in large B-cell lymphoma that are achievable with R-CHOP treatment today and to pursue a functional cure in follicular lymphoma.

On the next slide, I will highlight the latest data for both of these assets. We presented this past weekend at ASH. Moving to Slide 27. You see long-term 2-year results from our early phase study of frontline golcadomide in combination with R-CHOP in patients with aggressive B-cell lymphoma. All responses at the end of treatment were complete responses with MRD negativity rates of 90% or greater. These efficacy results showed that adding golcadomide on top of standard R-CHOP led to early responses with high rates of durable remissions. With a 24-month rate of duration of response of over 90% in the overall in high-risk patient populations. Taken together, these results demonstrated impressive 24-month progression-free survival rates up 79%.

On Slide 28, you can see that the adverse events for this combination were similar to what is seen with R-CHOP alone. We mainly hematologic events observed. The non-hematologic adverse events were infrequent and mainly low grade. Importantly, adding golcadomide to R-CHOP did not compromise the delivery of the chemotherapy regimen. Overall, this long-term efficacy and safety results supported the ongoing Phase III GOLSEEK-1 study, where we are investigating golcadomide, plus R-CHOP at [indiscernible] versus R-CHOP in first-line LBCL. We anticipate seeing this Phase III data in 2028. And while not covering today's events, our second Phase III trial for golcadomide, GOLSEEK-4 is ongoing. Also, we did expect in 2028. This study is evaluating golcadomide plus rituximab versus [indiscernible] in second line plus follicular lymphoma and offers a potential chemo free regimen, which is meaningful to these patients.

Shifting to Slide 29. I'm excited to share the ASH data for our first-in-class BCL6 ligand directed degrader. A new asset, we are starting in a diffuse large B-cell lymphoma and follicular lymphoma, also developed through our protein degradation platform. BCL6 is a key genetic driver of lymphomas. Most types of DLBCL and FL require BCL6 to maintain their cell proliferation and survival, making BCL6 a broadly relevant therapeutic target for lymphoid malignancies. The BCL6 transcription factor has historically been considered undruggable as opposite to kinases and other targeted enzymes. However, ligand-directed protein degraders can potentially target any type of protein, including transcription factors.

Data demonstrated that in heavily pretreated patients our BCL6 degrader as promising efficacy results with overall response rate of 65% in both DLBCL and FL. The safety profile consisted of mainly low-grade adverse events with no grade 4 cytopenias observed. We are encouraged by this preliminary results, and we continue to evaluate these assets both as monotherapy and in combination with bispecifics or rituximab across [ non-Hodgkin ] lymphomas.

Slide 30 shows our broad portfolio across both aggressive indolent lymphomas. It is worth mentioning the latest Breyanzi data just presented at ASH. Long-term follow-up data from our Phase III TRANSFORM study in second-line relapsed refractory LBCL showed the highest rates of 4-year median PFS and median OS seen so far in a randomized CAR-T clinical trial in this setting. This data underscore Breyanzi as the best-in-class CD19 directed cell therapy.

Then looking at our next wave of protein integrators, golcadomide and BCL6 we may have agents with transformational potential because these drugs are highly combinable oral options. We envision they may become new standards of care across DLBCL, FL and the other histologies we are studying through the early phase studies.

Let's conclude today's discussion before moving to Q&A. Turning to Slide 32. We have covered a lot of information today, but what I'd like you to take away is how we are uniquely positioned to transform how hematological diseases are treated. We are on the cusp of a new wave of hematology assets across our differentiated protein degradation and cell therapy platforms. As we head into 2026 I'm excited for the many pivotal and early-stage data readouts anticipated across our hematology portfolio. The near and long-term growth of the company will be fueled by new asset launches, the expansion of indications and our investment behind our innovative research platforms to change the lives of patients. I'm energized by our next wave of assets with their high commercial potential to solidify our leadership in hematology and help drive BMS into the future.

I'll now turn the discussion back over to Kate.

Thank you, Christian. We will now begin the Q&A portion of today's event. Operator, let's begin with our first question.

[Operator Instructions] The first question today comes from Evan Seigerman with BMO.

This is [ Mac Mosman ] on for Evan. I was wondering if you can talk about the -- how new comments in the FDA preferring randomized controlled trials with the comparator for new CAR-T and it may impact your planned GPRC5D development and regulatory plans. I appreciate it.

Thank you for the question. This is an important one. Lynelle do you want to give it a try.

Absolutely. Great question, Evan, and we certainly anticipated that, that would be a question based on the article most recently in [indiscernible]. First thing I would say overarching is while they have presented in that article is a new framework and a higher bar for CAR-T ironically, and every discussion we all have as a field with the FDA, they really encourage randomized controlled trials. And where we can do those, we do perform those as follow-on trials. But we also are able to negotiate with the FDA and most recently, a marginal zone was a perfect example of that, where we got approval on a single-arm trial with no requirement of a randomized controlled trial.

Now the good news with Arlo-cel, we, as you know, QUINTESSENTIAL, the initial trial is in relapsed/refractory is a single-arm trial, but we also have already in flight a randomized controlled trial, known as QUINTESSENTIAL-2. So we are encouraged and we'll pursue an approval on our later line trial, just as we have previously, and we'll look forward to the negotiations with the FDA, but are confident that we'll pursue an approval on that later line trial because we have in-flight a randomized controlled trial.

And allow me a more general comment. Everything is very much dependent on the quality of the drug and the product that you bring it to the agency. Because if you have a product with the transformational potential, this is independent of the modality, I think it is always willingness to bring it to the patients as soon as possible. And we also want and continue to collaborate with the agency with the fastest way and you can go with an accelerated approval in eventually a confirmatory trial like we do in many of these -- with these promising drugs. Thank you.

Thank you, Lynelle and Christian. Let's move to the next question, please.

The next question comes from Jeff Meacham with Citi.

This is Mary Kate on for Jeff. Just one on cell therapy here. So you walked us through the positioning of Arlo-cel and multiple myeloma. Maybe what feedback have you received from physicians regarding placing Arlo-cel in the treatment paradigm upon approval? Where do you think physicians can to use this treatment?

Lynelle, if you?

Yes, absolutely. So great question, and let me just start off by saying we were really excited about the opportunity to continue to share data at the ASH meeting and the excitement continues to grow on Arlo-cel, particularly as we see the BCMA field continue to expand. So patients are going to be exposed the BCMA in earlier lines at a greater degree. And so that really does present a great opportunity for Arlo-cel. But you also pointed out the other point. A lot of physicians have been talking to us and are happy that we're showing data both in BCMA exposed and BCMA naive. The efficacy, as you have seen on data that we presented, looks very similar, both on depths of durability -- duration of variability and depth of response.

So while the data looks very similar, we are pursuing this as a post BCMA asset. We do feel that the unmet need is very high. And as I said earlier, growing and the field is certainly looking forward to having a CAR-T as an option there, because as you know, the disadvantage right now is they have one agent to be able to provide patients who have been exposed to BCMA and its [ golcadomide ], it's a BCMA-targeting TCE. That agent, while it has efficacy benefits, it also carries some liabilities when it comes to on-target off-tumor side effects that have proven to be very difficult for patients to tolerate.

And so for us, with a CAR-T, where you're putting pressure on that target once, you're seeing those efficacy benefits you'd like to see and even greater depth with a CAR-T, but not seeing some of those off-target or -- sorry, on-target off-tumor liabilities that you've seen with the TCE. So we're quite excited about Arlo-cel, and the field is eager for us to get this asset on to market.

The next question comes from Matt Phipps with William Blair.

I was wondering if you still plan to file iberdomide for accelerated approval based on the MRD results of Excalibur. And then for the dual BCMA GPRC5D. What I guess, do you think you need to see to move that program forward? Is it higher initial CR rates trying to beat the 70, 75 rates we've seen so far with BCMA? Or do you really need to see more durable CRs from the dual targeting?

Thanks for the questions. Maybe Rosanna, I want to give an update on where we are with Iberdomide and the registrational discussions on going?

Sure. So as you've seen from the press release that we issued, we were pleased to announce that the Excalibur relapsed/refractory study did achieve a positive MRD-negative CR readout. And as you know, that's an important milestone for this program coming from the FDA ODAC last year where they voted unanimously on the utility of MRD negativity as an accelerated endpoint for regulatory action. We intend to discuss with the health authorities this the potential to bring this asset forward.

You've seen from the clinical data from our Phase I study that the combination of iberdomide with daratumumab and dexamethasone is highly active. And compared to historical lend has improved and the outcomes with faster and deeper MRD. And so we're very excited about the data, and we'll see how negotiations go.

So as you know, we will guide on final acceptance in the moment that we will have final acceptance. What I want to add is we didn't present these results at ASH, have you noticed that because PFS that it is the second dual endpoint is so important also in the context of any regulatory interaction that we are having that, of course, we don't want to jeopardize that end point, rushing into presenting the data. We are very excited by -- this is the first readout, and we'll keep you posted on this.

Let's move to the second part to your second question, Lynelle you want to maybe explain the value of effect work at?

Yes. As you probably know, obviously, we first started really pursing this when we started pursuing GPRC5D. We want to first prove that, that target, we could actually effectively hit that target with the anticipation that if we could, we would actually move into a dual targeting approach. And since that time, there has been clinical data that has shown different modality that hitting those 2 targets does create greater durability and duration of that durability. So that is an exciting place to be when you think about multi-targets.

Now the question you have is what will a onetime infusion hitting a GPRC5D and BCMA need to be for us to continue to pursue this. For us right now, what we're looking at is 2 things. One, the efficacy which you articulate. We are going to need to see high CRs and high ORR rates to clear the hurdles of what we see today on single targeting agents. And certainly, we also are watching the field from other modalities and what we need to say to ourselves, what does the field need? And what we hear from physicians and why this is one of the fastest accruing trials that we have in our self-therapy portfolio is because they want a curative intent modality to move into earlier lines, and they do not feel in the field today, they have that.

There is liabilities with some of the other agents and what they would like to be able to provide a patient in earlier lines is something that provides them that curative intent without some of the permanent liabilities, especially knowing that patients with multiple myeloma live for years. They go through multiple lines of therapies. So when they think about CARs moving into earlier lines, they want one that they feel is going to give them the efficacy without all the liabilities. So we certainly have a high TPP for this asset across efficacy and safety, but I can tell you indications of our clinical trial recruitment is one of great exuberance and excitement. So we're looking forward to be able to sharing data, as Christian shared earlier in the presentation next year.

And I'll just add to what Lynelle said and described the dual targeting construct and how we feel this differentiates. We optimize this by specific construct so that it overcomes variability in patients' antigen expression. It is leveraging the binders that we have with Arlo-cel and Orva-cel, so not Abecma. And it's a tandem loop design that has advantages in product uniformity, potency and persistence. So as we move this into newly diagnosed, we do have a true secure intent.

So Matt, I hope that you feel how excited we are with this second CAR that we want to bring into the clinic and how differentiated potentially can be. It's at the beginning of the journey, but we will -- you will see how is delivering the expectation.

Next question comes from Luisa Hector from Berenberg.

Christian, good to hear from you. I wonder if you could just expand a little on your vision, particularly of the first-line myeloma treatment paradigm because it's become pretty complex, and there's a lot of studies ongoing that will read out. So how do you think about that frontline? Will it become simplified what is your level of confidence that Bristol-Myers therapies will participate here? Or should we be thinking about your franchise, perhaps as more second line plus.

And then if I could just check on the CELMoDs, you're talking about being the backbone -- potential new backbone therapy. Is there anything we should think about in terms of overlapping toxicities with partner drugs or even with BCMA T-cell engager is there anything to think about there if the CELMoDs are going to join other products?

Hi, Luisa. Very nice hearing from you. Very complex question. I will not expect anything less from you. So first of all, let me start with the frontline. You are right. The frontline myeloma is becoming a very incredible complex space. And I think it's a good thing. It's a good thing because it means that we can -- everybody of us can bring to patients novel and different treatment options.

I want to link back a little bit to what Lynelle was telling. As a company, BMS would like to bring cure to these patients. Today, the myeloma has been an increment -- first of all, an incredible successful story, if you think where Myeloma was a few decades ago. The patients today are surviving almost normal times because all the advancement has been done in this disease, but it's a sequence of one treatment at the after the other. The question that everybody is asking is, can we bring something curative upfront and ultimately solve problems since the beginning. And this has been done in other diseases. You need probably something more than what you have today.

So this is why I believe everything we are doing in the development of the next generation of CAR-T cells, I think, is very relevant here. Because this is one way to bring cure probably, and we have seen in other indications. So it's one thing. And the CAR-T not necessarily can be delivered by itself. And here, I want to link a little bit with our CELMoDs strategy because what we are doing with either is adding either after CAR-T because we know that this can bring benefit in -- after transplant, but the concept is the same. We want to integrate other modalities to what can be potentially curative, but not necessarily can be in every patient. This is where we believe integrating a portfolio like ours with multiple shots on goal can give us this opportunity.

For the role of CELMoDs, I am absolutely excited by this drug. First of all, Luisa, protein degradation has always been a very important aim in research and in development. And I think BMS as a platform, they put the company not honestly upfront there because it's something that is in research and since many years. There is the highest level of knowledge. We have currently 11 drugs in clinic between hematology and oncology with targeted product degradation. And it's not only terms, there are -- we have ligand degraders. We have an antibody conjugate degraders. So it's really a platform that can deliver.

The great thing of this thing is that these are oral drug, these are pills that you can combine very nicely with other treatment. Of course, there is some toxicity associated with some of them. But this is why we have such a large portfolio because, for instance, we know that Mezi is a very potent CELMoD and more difficult to be combined with anti-CD38. This is why we are using Mezi with PIs and we use either that is more combinable with data in that space. This allows us to position these drugs across the spectrum of treatment.

So to wrap up, what I would say is first line, absolutely, we want to play them and we want to bring cure to this patient and early diagnosis the space to be. But there will be inevitably some patients that will need further treatment, and this is where we believe building regimens with our portfolio will help us to deliver this.

And maybe building, Christian, this is exactly an exciting time for patients with multiple myeloma, and the BMS portfolio is extremely well positioned. As you've heard with CAR-T and also with our CELMoD coming off ASH, what we've really heard from clinicians is they see that Iber and Mezi are now going to be the partner of choice whether you're talking triplets, quadriplets, whether you're talking in combination with TCEs, we also already have as part of our registrational program for Iber maintenance study which is, of course, a highly important segment for these patients.

And what our clinicians tell us, and this is a study that's recruiting very well is that they can tell when patients are on iberdomide the number of GI side effects and fatigue, which are particularly important when you think about our previous image therapies, they're seeing this as very much lower. So this is definitely a group of products that show broad applicability, high quality of life for patients, not only in academia, but also in community and as the field starts to evolve with TCEs coming in earlier, we are also ideally place as a partner of choice there. You saw magnetism and MELT data coming out of ASH. That showed to your point, a reassuring safety profile in combo. And we're seeing from our clinicians that this is probably an ideal combo in a setting where people may have already had [ dara ] early on.

The next question comes from Steve Scala with TD Cowen.

Just a follow-up to Luisa's question. How has the approval of Blenrep changed Bristol's view on how the multiple myeloma treatment landscape will evolve in the U.S. Does Bristol view Blenrep as an important potential combination partner? Or do you not expect significant use of Blenrep in multiple myeloma?

Steve. Nice hearing from you. Let me start. I see this approval as a positive thing for patients like always. Of course, we know what are the strength and potential some liability with ADCs in this space. So I want to -- Rosanna maybe give a little bit of your view on this approval.

Sure. The Blenrep approval in third-line plus relapsed/refractory myeloma was with BVD post and [ IMiDs and PI ]. It is it is limited, it rejected the second-line use, but it's a good option for patients in late lines when other drugs have failed. The ocular toxicity will be a logistical and practical burden. Using Blenrep early, we have heard from physicians and investigators can limit the effectiveness of TCEs and CAR-Ts and actually the International Myeloma Working Group recommends using ADCs after TCEs in CAR-T.

If we look at our CELMoD program, as Monica was talking about, these are orally convenient drugs that can be used across a wide range of treatment settings across patient populations, easy to use and administer with side effect profiles that clinicians are used to managing from -- so I think we are well positioned with our myeloma strategy.

So Steve, all in all, it's a positive. Blenrep was approved because it's another option for the patients, but also because it gave us the confidence that there is still the space to bring potentially even better drugs there and building better regimens. So the agency is open to this approach.

Next question comes from Courtney Breen with Bernstein.

Actually I wanted to follow up a little bit on Luis' question about the first-line multiple myeloma crowding context. And particularly, as we think about kind of Ibern and Mezi, perhaps replacing some of your older agents. Can you talk a little bit about how we should think about the potential size and scope of the TAM for these CELMoDs relative to kind of that replacement opportunity for Revlimid and Pom given kind of this evolving landscape and perhaps greater competition and different options available to physicians.

Thank you, Courtney, for the question. I would ask maybe Rosanna to try to give an overview of where we are playing with the different studies and the view. And maybe, Monica, can take the second part of your question, Courtney.

Sure, absolutely. Multiple myeloma has always been a rapidly evolving treatment landscape, and that has not changed. Our portfolio is built for a future treatment paradigm. If we look at how treatment has changed over the decades, IMiDs has been the consistent backbone of therapy, and CELMoD were deliberately designed with a deep understanding of the biology of images and they offer a more tailored approach of potency, tolerability and combinability.

Aside from the scientific rationale, we now have compelling data that shows the improvement that CELMoDs can bring. Christian reviewed the EMN '26 data of Iber replacing lenalidomide. It doubles the MRD conversion rate in the post-transplant setting compared to LEN in modern trials, and we're excited about the Excalibur maintenance readout.

The other thing that we saw is from our MMO 1 study, [ IberDd ], in newly diagnosed transplant not intended, we saw faster and deeper MRD compared to historical lend more than double the MRD rate. And so that, along with our ambition with our dual targeting CAR in newly diagnosed, we feel that we have a portfolio that is built for the future of treatment paradigm.

Yes, absolutely. And from a commercial perspective, REV and POM has been extremely popular for very good reasons. They are extremely easy to use. The majority of patients still sit today in community where having an oral accessible treatment for patients is highly appreciated. And in Iber and Mezi, you basically have the next generation or as some people have called them super and its where you have even more potency from an efficacy standpoint, but also this improved side effect profile, which many patients, particularly when you're thinking of a maintenance therapy, which is, again, a large segment of the population is extremely valuable to patients.

So we really do see Iber and Mezi replacing the backbone being the partner of choice for all of these new therapies coming along. And the emerging data that we're seeing in these combination treatments is extremely reassuring from a safety perspective.

The next question is from David Amsellem with Piper Sandler.

So sticking with the commercial landscape for Iber and Mezi. Can you talk to access and affordability for those 2, particularly earlier lines of therapy in multiple myeloma in the context of a world where the IMiDs are going to get a whole lot cheaper over the next few years just in terms of generic competition. How do you think about that?

Monica?

So of course, I can't talk specifically about price, but what I can say is that we believe that we have a product that shows significant value for patients. This is a regime that's going to be able to be used both in community and academia. And as the multiple myeloma landscape evolves, we believe that these products represent value for patients and for the physicians that serve them.

The next question comes from Zach Dunn with Guggenheim Securities.

This is Zach Dunn on for Seamus Fernandez. So firstly, we've been encouraged by the growth of Breyanzi. I'm wondering -- can you elaborate on what is driving this growth? And where do you see market share ultimately ending up? And if you can address U.S. and OUS, that would be greatly appreciated.

And moving to your BCL6 degrader. It seemed at ASH, there were some questions on the correlation between BCL6 expression at baseline versus response and how -- there doesn't seem to be a clear correlation at this moment in time. I guess, can you provide a little more guidance on how you're selecting the right patients? Or do you think that this drug will be more reserved for follicular lymphoma, given the higher CR and ORs in this population?

Thank you, Zach. Very good question. Let's start, Lynelle with Breyanzi.

Yes. Thank you so much, Zach. And thank you also for noticing Breyanzi's significant growth this year. You are right. We became the #1 CD19 CAR-T in worldwide sales on last quarter, which was a great milestone to achieve, particularly since we launched third to market and spent our first 3 years vector constrained. And so now enjoying being unconstrained and manufacturing success rates in the 90s, it's really allowed the overall profile from efficacy and safety and now manufacturing to really be now the asset of choice at ASH, in particular, if you didn't have the opportunity to see, there was 2,400 patients worth of real-world data presented across France and the United States, demonstrating the comparison of liso-cel and axi-cel in that data set, you've got to see that these assets are very similar on efficacy, if not very similar. And then on safety, they're highly differentiated.

And this is why we do believe we became the #1 CD19 CAR-T while we are being fueled by our broad set of new indications, and that is a differentiator for the asset. I think the overall profile, if you just clicked in LBCL. We are now the #1 asset also in LBCL which is the largest indication, and that isn't just in the United States, that's in Japan, Germany and France, in the major markets. And the reason for that, again, is because they're enjoying the efficacy of a onetime infusion from Brand, but also not having some of the liabilities that CAR-Ts can bring. And so it really has been agreed last year for Breyanzi, and we do anticipate that growth to continue based on the broad indications and its overall profile.

Your question about split between international and U.S. We do anticipate the international markets will still accelerate maybe at a faster pace in the United States because they kind of -- we launched later there, and we were constrained later. So those -- we're bringing on additional markets -- 12 additional markets as we move into next year. So with the expansion into new markets as well as greater penetration into the major markets that we launched into, I do anticipate Breyanzi will continue to grow.

Thank you, Lynelle. Rosanna let's try to give a little bit of an overview on the BCL6.

Sure. So BCL6 is the Ligand degrader is has been shown to induce rapid and sustained BCL6 degradation in both the peripheral blood and in the tumor. Remember, this is a hetero by functional ligand degraders. So it degrades BCL6 through the cereblon E3 ligase recruitment ubiquitination and subsequent proteolytic processing. And so you not only have degradation of the BCL6 but you also have activity from that CELMoD platform. We have ongoing investigations, of course, in our translational development to look at how BCL6 acts in the tumor.

We know that phenotypically, it modulates T follicular helper cells and T regulatory cells without affecting cell viability. And so there is a multi-modality approach to using this asset, and we have ongoing investigation so that we can understand how to best enrich for responses as we move the development forward.

Thank you, Rosanna. Zach, let me add a couple of thoughts. Personally, I'm really excited about this novel degrader. First of all, BCL6 as a target has been chased for decades with our success, and now we have a drug because you have seen the monotherapy that is very clear. I think your question on, can we identify patients can benefit even more is very relevant. And as you can imagine, we are working very hard to understand.

Rosanna gave you some very clear explanation why the drug potentially can still work in most of the patients and all the patients. There is another aspect I want to highlight and is the safety profile of the drug. The drug does not induce cytopenias or no severe cytopenias. So the combinability that you can have with the BCL6 maybe is different than the combinability you have [indiscernible] It is more on the classical cytopenia toxicity, hematological toxicity. So this is another very relevant drug in our portfolio of lymphoma assets that can give us the flexibility to, again, continue to build on other regimens and targeting something that is so far has been undruggable.

So it's the beginning of the journey, again, but actually, we have a solid monotherapy data. And as you can imagine, we're starting a very broad combinatory strategy with the drug across modalities.

Thank you. Operator, we will now take our last question, and then I will ask Christian to make closing remarks.

The last question today comes from Kripa Devarakonda with Truist Securities.

Maybe a follow-up on the prior question. As you develop BCL6 combos for second-line of BCL. How do you think about the eligibility of patients for the combinations versus cell therapy? And maybe on Breyanzi, as you're seeing increased access and growth, any changes in how you're thinking about pricing and market access?

Thank you, Kripa. Maybe Rosanna try to give a little bit an idea, of course, we don't guide on the inclusion/exclusion criteria that really matter...

Sure. Sure. So when we look at our -- both in myeloma and lymphoma, when we look at our CELMoD portfolio and our cell therapy portfolio, we view them as complementary and not really competing with one another. And so without giving away too much about the inclusion/exclusion criteria and how we're moving forward in the pivotal trials, we do see that the oral convenience of BCL6 in patients with non-Hodgkin's lymphoma makes it a nice partner for bispecifics. And we are very much looking forward to the combination strategies that [indiscernible].

And then Kripa, you actually asked a really good question in reference to Breyanzi and its growth that I didn't mention touching on market access, but it's underlying your question is where we're also getting a lot of our growth is into the outpatient and to the community. Obviously, growing CAR-T as a class is an enormous strategic priority for the industry. And certainly, Bristol-Myers is a leader in this industry is doing a lot to partner with the community and being able to deliver CAR-T at the major community centers.

And we're really happy to see multiple CAR-T community practices now come on board and be treating patients in the community. That said, there is no challenges we have faced yet nor have the treatment centers. That was one of the biggest concerns was how were they going to get reimbursed. Would they be getting reimbursed. And we're really happy to say, I think that was a lot of concern and perception, but we've been able to navigate the market access landscape in the United States and the community physicians are getting reimbursed for CAR-T. So we have not been facing challenges on pricing and reimbursement with Breyanzi.

Thank you, Lynelle. Operator, let's close.

This concludes our question-and-answer session. I would like to turn the conference back over for any closing remarks.

Thank you for joining today in this Hematology Drug Development Update. I really hope that you found these latest data, this pipeline insight and the strategic perspectives that are informative but also inspiring because we continue and we wanted to advance these therapies for patients. I'm really looking forward to sharing more progress and especially some of the pivotal milestones next year.

Thank you for your questions and have a great rest of the day.

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

Geoff Meacham. I'm the senior biopharma analyst. And we're thrilled today to have Bristol-Myers with us on stage. We have CFO, David Elkins. We also have Adam Lenkowsky, Head of Commercial. So guys, welcome.

Good to be here. Thanks for having us.

Well, we have a number of questions to go over, partly finance, partly commercial. But maybe for you guys, let's just talk about yesterday's news with respect to the Cobenfy study. That's probably the more topical thing to give us some context for kind of the trial amendments.

Yes, happy to do that, Geoff. So as you're aware, yesterday, we announced that the ADEPT-2 study would continue, and we would enroll additional patients into the study. If we take a step back, if you remember, on our Q2 earnings call, we talked about conducting clinical trial site reviews across a number of our near-term priority studies. And as a result of those clinical trial reviews, we did find some irregularities as it relates to the ADEPT-2 study. So we then immediately reported that to the data monitoring committee as well as to the FDA. And in consultation with the FDA and the DMC, the decision was made then to exclude a number of sites and all of those respective patients from the study.

The second area was, again, an agreement with FDA and the DMC was to conduct an interim analysis looking at both efficacy and safety. The DMC then met and told us to continue the study as planned. We remain blinded to the data. So this is all done prior to the database lock. And the recommendation was to increase the enrollment back to the original sample size of approximately 400 patients. So again, that study will continue. We now project that study to read out sometime in the back end of next year, right around some of our other data readouts for ADEPT, ADEPT-1 and ADEPT-4. And taken together, remember, we need 2 positive studies to hit, and we've got 4 studies now in flight, ADEPT 1, 2, 4 and now ADEPT-5 as well. And so we feel good about the probability of success for our ADEPT program and the broader Cobenfy development program.

Yes. Maybe we'll focus first on that on Cobenfy as a franchise. So in the schizophrenia setting, the -- maybe talk a little bit, Adam, about the success so far as you wins along the way on things like formulary on adoption, awareness, then we can get into maybe the investments that you're making in future studies for sure.

So we just passed around a year on the market, and we feel good about where we are at this point in time. We had very early on, achieved strong access position, both in Medicaid and Medicare. And now we have a strong access position in the commercial setting as well. This is a space that's dominated, as you know, by government payers, Medicaid and Medicare.

One of the things that we're really pleased about is we're looking at now surpassing 2,700 TRxs on a weekly basis. And so we're approaching 3,000 TRxs, which now far exceeds any other schizophrenia launch in the recent years. And so what I look at is how are we doing adding new prescribers, what's happening with TRxs and NBRxs. And we talked about our acceleration plan, which we've added a number of new salespeople on the ground to improve our reach and frequency as well as entering into the hospital setting where a number of prescriptions are initiated, roughly 20% to 25% of prescriptions are there and we've launched DTC. And since we've done that, you could see a nice acceleration in both NBRx and TRx growth as we end the year.

And so we feel good about the momentum that we have coming out of 2025 and into '26. And as we've said, we think this is going to be a big product in schizophrenia. And certainly, when we get additional indications, this will be a very big product for the company.

What's been the education cycle for -- given the novel mechanism, right, the muscarinic -- is there -- are there some neurologists, some physicians overall that still need a bit of an education of how the drug works. There hasn't been a lot of innovation, I guess, in many years. And so you have to sort of prime the pump, so to speak. Are you still doing that, I guess, are you...

Absolutely. Look, there's been nothing new in this space for over 3 decades. So when you look at the psychiatrists who are treating schizophrenia, setting appropriate expectations, reinforcing a differentiated profile and really trying to unlock what has been entrenched prescribing behaviors for decades with generic D2s have been critically important.

I think most importantly is really around how do you dose the medication? How do you set the appropriate expectations on? What side effects to expect? And when you look at Cobenfy's profile, you truly see unprecedented efficacy with a side effect profile where you don't see the side effects like EPS, prolactin, weight gain, sedation, which have plagued the generic D2s and quite frankly, the entire class. So this will continue into next year, and we'll continue to have more data from Phase IV and from the real world to best inform our psychiatry community.

Got you. Makes sense. And I know you're -- so let's talk about the future trials to go after. So obviously, Alzheimer's, you have a lot of the multiple depth studies. But talk about the other indications. I know you guys were talking about at one time, bipolar. There's a lot of different other segments where the mechanism may work. Beyond the ones that you've announced, are you thinking about making this another 5 or 6 trials? And maybe what would be on the docket?

Yes. So this is a great question, and we've got a number of these programs already up and running. So obviously, we've talked about our ADEPT program, and that's for Alzheimer's disease psychosis. And when you look at the roughly 6 million patients with Alzheimer's disease, roughly 30% to 50% have hallucinations and delusions. But we also have studies in Alzheimer's agitation and Alzheimer's cognition, which is really what got us excited about this asset, the differentiated property looking at cognitive benefits for this mechanism.

We have a bipolar studies that will likely read out towards the end of next year or into early 2027. We have studies that were standing up in autism irritability and now we're looking at additional indications to bring into our development plan.

Got you. And does the -- are you looking at the ADEPT studies looking to end of next year. As the gating factor, do you want to see more positive Phase IIIs before you decide to invest in future indications?

We've already stood up those studies. So we're going to go forward with those studies. We've got good proof of concept from early data that we've seen. And when you look at the program that we have, in bipolar, we're looking at exploring that in bipolar mania, and you see very similar symptomatology that you would see in schizophrenia with delusions or manic behavior and then the same with psychosis of Alzheimer's disease. So we feel good about the program that we have and confident about how those studies will read out.

Well, let's take it a little bit higher level. So I know this internal R&D is a big component of the Bristol story and the growing pipeline. Maybe David, can you talk a little bit about kind of the pushes and pulls on the P&L as we look to next year. Obviously, you have the new product portfolio, where there's a big investment in the success there commercially, but I want to get your perspective of kind of some of the puts and takes.

Yes. Thanks for that. And really, first, if you're talking about it as we think about as we're going forward, think about what we've accomplished this year in 2025. And it's been a strong year from an execution perspective, particularly on the commercial side. You're really seeing the transition of the portfolio to the growth portfolio, which is now more than 50% of the business in the most recent quarter growing 18%. And it's pretty -- that portfolio in itself. We now have 4 products in there that are annualizing over $1 billion. Reblozyl is annualizing over $2 billion. Adam very nicely laid out Cobenfy and the traction we've been making this year on and adding that to the portfolio.

But also next year's '26 is a really important year from a catalyst perspective. If you think about the number of NMEs that we have Phase III data readouts, you guys are going to hear more. I'll start with the CELMoD. We have iberdomide and mezigdomide. We're really excited about those 2 products. We see those that could be next-generation Revlimid and Pomalyst, great from an efficacy and a safety perspective. ASH, you'll hear more about that. We also -- LPA1, which is in pulmonary fibrosis and really is a high unmet need.

Really excited about that product, adding that to the portfolio, and we'll have Phase III data there. And of course, milvexian. We have 2 important studies reading out next year there with secondary stroke prevention and AFib. So as we think about 2026, there's a lot to be excited about from the portfolio, but as well as continuing the growth of the growth portfolio.

So our focus as we head into '26 is continue to drive the growth portfolio, continue to execute against the pipeline. And then obviously, our efficiency programs that we've laid out. Last year, we had an expense base was about $17.8 billion this year. We got it $16.5 billion. So we've made really good progress on those efficiency programs. We said about $1 billion we'd achieved this year. We feel really good about that. We have line of sight for an additional $1 billion of savings that will be achieved in '26 and '27 and that gives us a lot of financial flexibility. Not only does it give us flexibility to invest when we bring in new products through business development, but it also provides cash flow for us.

So I think it's a muscle that we, as an organization, we see even further potential to drive efficiencies there. So as we look at '26, we feel good about where we are from a growth trajectory. We feel good about where we are from driving operational efficiencies and what can do from driving earnings. And then we also feel really good about our cash position. We had $17 billion in cash at the end of the third quarter. That's going to enable us to continue to strengthen that portfolio by bringing in more products.

So David, talk about the cost savings. And I know a lot of companies have deployed things like AI to drive efficiencies. To what degree have you guys go -- gone all in on that? And has that been more surprising or in line with kind of what you thought in terms of the level of cost efficient?

Yes. It's a great question. I mean, really, AI is -- we're excited about this, and it's not just from an efficiency perspective. From an AI perspective, we see the greatest opportunity and driving shareholder value by helping us accelerate identifying new medicines, accelerating to proof of concept. And then even -- and we're using it even in study design, helping a site selection of drug development side of things. And it's even making us more efficient on the manufacturing side, I think where we're able to predict problems in manufacturing processes before they occur by using AI. Again, all of these things drive efficiency.

But more importantly, if we can increase our probability of success in early development that we can speed the time between proof of concept and product approval by using AI, and we got some early test cases there that we believe that's going to enable us to do that. We'll be able to bring more medicines faster to patients, which does where you create the shareholder value. We are getting efficiencies. A couple of examples around that. It's critically important, like simple things that like automating approval processes, even in the finance organization and the procurement organization, simplifying the procurement process for our scientists and our sales force. So we're spending less time doing internal processes and more focused on the external world, whether it's being competitive or more time in the lab, we're using AI in those cases as well. And of course, it helps us drive those efficiencies that we've talked about earlier.

So the last sort of financial sort of P&L kind of question you mentioned, I mean the good cash, net cash and also cash flow. But I wanted to ask you on capital deployment, and you guys have done a ton of deals over the years, and they've added a lot of exciting new products to the mix. Maybe where does this rank in the priorities now, now that your new growth portfolio has really -- new product portfolio has taken off? And are there spots that you're not in, but maybe what's the level of the threshold for adding in TA or expanding on what you already have?

Yes. It's another great question. And look, we think we have plenty of substrates within the TAs that we currently have. And as you already said, we feel really good about where we are in that growth portfolio. And what we have, just the number of data readouts and just remind you, we have the potential for 10 new NMEs by the end of the decade and 30 additional indications by the end of the decade. So we do have a lot of substrates. So from a business development perspective, we're going to continue to look for those areas where there's high unmet need, where we think there's really good science from a modality perspective that can address it and where we can add value and bring down cost to the overall health care system.

A great example is just look at the deals that we've done this year, whether it's cell therapy, we see as a tremendous potential for us in immunology and doing orbital therapeutics by doing in vivo will really bring down the cost, the potential to bring down the cost of cell therapy to bring it to a large market like in immunology. We had some really interesting early stage studies that we're excited about that. The other thing I would say is that look what we did on radiopharmaceuticals. We don't talk a lot about that. Huge opportunity for us. We see it as an IND engine. We added to that this year with PhiloChem.

And then lastly, I would say, look at the BioNTech partnership. There is an area of solid tumor oncology. We have a very strong position. We believe this is -- has the potential to be standard of care and we have a really robust development program that we're working on with BioNTech there. And we see that being able to go into multiple tumor types. So those are the types of deals that you'll continue to see us do. They're going to be in therapeutic areas where we have deep scientific knowledge and have commercial acumen. And we still see plenty of potential there to continue to do, whether it's partnerships or acquisitions in those areas.

Okay. That's helpful. Well, let's talk about some of the assets and new product portfolio. And one of the questions we get a lot is a Subq, Opdivo, the new launch [ kinetic ]. So if you think about the maybe the access and the initial kind of demand. Obviously, the idea for you guys and for Merck too is to roll this out in patients that are maybe pre metastatic, healthier patient. But over time, though, to potentially just let the metastatic kind of end of things, play out with respect to biosimilars. But just talk about how you're setting the stage for that with the Qvantig launch today.

Yes. We're pleased with what we're seeing with the Qvantig launch. Also, we launched right around this time last year, so a year on the market, and we're seeing really good conversion from the IV over to the subcu. One of the things we talked about was once we received our permanent J-code, in July, we see that July 1, we would see that inflection in sales, and that's what we have reported in Q3, a really nice jump in sales, and we expect to see continued strong conversion over time for this formulation.

What we're hearing from physicians and patients the convenience of a 3-minute in office, a subcutaneous injection is incredibly patient and provider friendly. About 70% of the use now is in the community where the majority of patients are treated. And we're actually seeing broad utility across a number of tumor types.

So it's not just in the monotherapy or adjuvant indications, but we're seeing use in combination where a combination with YERVOY or combination with TKIs or chemotherapy. So we expect to see continued conversion from now to LOE. And as we had shared, we expect to see 30% to 40% of our IV business converted by the 2028 time frame.

Adam, can you sort of -- I wouldn't say force, but can you drive use in one versus another based on things like the gross to net or discounts or volume or I'm trying to get a sense for how you can maybe further strike point [indiscernible] the paradigm?

Well, clearly, in the community, they are very economically driven, and that's why you see the majority of the use there. I think number one, the advantage of a 3-minute in office injection versus a 30-minute to 1-hour infusion is that you can inject the patient and at the same time, fill another infusion chair or a suite in the community. That's number one.

Number 2 is when you look at net cost recovery, there are benefits to using the subcu over the IV formulation. And so that is going to be a determining factor. But the major determining factor really is around the convenience that it offers to patients and the benefits to physicians.

Okay. That's helpful. Sticking with oncology. So cell therapy overall, you guys are among the largest cell therapy companies out there on the back of the Celgene deal. Talk about maybe, David, where this ranks kind of in your new product portfolio like priorities with the investments that you're making, this isn't a category where you could sort of be passive or you have to invest in infrastructure and manufacturing and consistently. So maybe talk about like the priorities of where this ranks?

Yes. Look, I mean the good thing is we're blessed with numerous modalities in oncology and hematology. And this is an important franchise for us, and we've really focused that the dedicated team of doing that. I'd say for Breyanzi, just tremendous success in a number of indications that are there, the broadest indications in its class. I think the other thing is that we have a follow on. We have Arlocel, which is do targeting, which we're really excited about. And then as I already talked about, NEX-T, CD19, we see that as the opportunity to go into autoimmune diseases. And then if you throw on top of that, the in vivo that I was talking about with the Orbital acquisition, being able to bring down those manufacturing costs, it makes it a really attractive franchise for us.

So it's an important component to the overall growth story. And this is the great thing about us. I think whether it's immuno-oncology, whether it's cell therapy, radiopharmaceuticals, and even with our iza-bren with our ADC, we have a lot of modalities, which is what we've been focused on from a business development perspective but as well as from an internal development perspective, that enables us to go after the most interesting science where there's that high unmet need. And that's why we feel really comfortable about our growth trajectory as we exit this decade because we have a lot of breadth and depth across really important tumor types.

One of the more exciting mechanisms is your partnership with BioNTech and the VEGF PD-1. Talk a little bit about that in terms of the -- maybe the context for forming that partnership like what was the -- did you -- what was the kind of background for how you're exploring that as a modality? And then going forward, you've invested in a ton of studies and maybe what's more exciting to you as you expand that offering?

Yes. I'll start at a really high level, and I'll turn it over to Adam. But look, this is a great example of how we think through business development. This is a really exciting area and it's an area that we've been following very closely. There is multiple options to enter into this. But look, we are looking for the best science. We're looking it's very important to be first or second to market because that's where the greatest value is generated in this place, and you can see that in IO today. And then do we have a right to win? Do we have the scientific expertise, do we have the development capabilities and do we have a commercial organization that can add value beyond in the hands of somebody that currently owns it?

When we looked at the entire landscape that was out there, we became most excited about biotech and where they are. They're just really strong from a scientific perspective, but our capabilities in development and in commercial really complements their scientific capabilities bringing those two organizations together and being able to do that in a joint partnership, 50-50 partnership, we think that adds the most value for both us and biotech. You want to talk about the programs?

Yes, just adding, we've been leaders in this space now for nearly 2 decades, starting with the launch of YERVOY back in 2010. And then we -- looking at the launch of Opdivo and of course, Opdualag. So we're the only company that's launched and commercialized 3 IO assets. So we think this was a great fit. The partnership is going very well. We've got 5 studies that we have announced, 3, which BioNTech had up and running in first-line non-small cell lung cancer, that is the largest opportunity for the category.

The second is small cell lung cancer in first line. And then we'll be presenting data over the next week or so at San Antonio Breast symposium in triple-negative breast cancer, and that's the third study we have.

On the earnings call, we also announced studies in first-line gastric cancer. And what's really exciting is the potential to broaden beyond where we've seen PD-1/PD-L1s work. So we had announced the study in first-line MSS CRC. And so that's going to be another important opportunity to expand what today is a $40 billion to $50 billion category even further.

Are there lessons to be learned from the pace of new Phase IIIs and the development of Opdivo, the lessons to be learned that you can translate here in terms of not be linear or just to more of a basket kind of approach to am I hitting the right?

No, absolutely. There are a lot of learnings to be -- I think when you look at the number of PD-1, PD-L1 VEGF that are being developed today, most of them in China. I think it's -- what we see today in these first-generation PD-1, PD-L1s are going to pay out in comparison to the number of these new assets that are coming to market and coming to the market quickly.

So as David said, I think the first learning is being first or second to market is absolutely critical because when you look at Opdivo and KEYTRUDA, together, we command about 80% of the marketplace today. In fact, when I think about where we compete with Opdivo, we are -- have the leading market share in the majority of tumor types today with the exception of lung cancer where we were later to market. That's number one.

Number two, I think that the importance of having infrastructure in place in the community, in particular, is essential because that's where the majority of PD-1, PD-L1s are treated. And so that's where we have a stronghold and I think a true competitive advantage in the U.S., but also we've got a global footprint, as you know, with Opdivo and Opdivo Yervoy and then the third, I think the velocity of new indication launches are really important. And as David said, we have that muscle to be able to flex and be agile from one indication to another indication in order to maximize those opportunities. I think those are some of the learnings that we have beyond -- I guess the final one is around the importance of non-registrational data generation because the data that we generate is always going to move faster than label can move. So the non-registrational data is critically important.

And Adam, you mentioned China and all the competition. Maybe, David, when you think about BD back to that question, we've seen a ton of new products coming out of China and a ton of new deals. And then in the U.S., it's kind of odd. We've seen a lot of CVR kind of deals. So we've seen some new structures emerge that really haven't been like that widespread in the biopharma space over the past couple of years. How does Bristol think about sort of deal structure? Do you -- and maybe give us some context for the emphasis of assets coming from China?

Yes. Look, I mean, we're agnostic where the asset comes from. It's where is the most important science, where do you have proof of concept and what assets are available and then what value can be created from those. So look, China is critically important. And if you look at the number of INDs that are coming out of China now globally, they're becoming a greater percentage of the total, and they can surpass the U.S. by next year. So you can't just ignore any geographic area, especially if they're producing that much science.

Secondly is, from our perspective, we're putting scientists on the ground there. We have business development teams there. We're looking for -- and it's a great way to get products into humans as quickly as possible to get to proof of concept. So it's critically important to the development cycle as well. That being said, look, there's a tremendous amount of science here in the United States and in Europe, and we look across the Board to find the best science for that unmet medical need.

Makes sense. So going through kind of the rest of the pipeline, so milvexian, you mentioned that. So talk about the recent discontinuation of the study and what gives you confidence in the other two studies with respect to read-through?

Yes, Geoff. So we announced with our partner, J&J, that the ACS study, we had a futility analysis and it did not hit the threshold that was needed. So the IDMC recommended to stop the study because of the low likelihood of hitting the primary endpoint. So as we commissioned that study, we knew that was going to be the highest risk study that we put forward. We haven't seen a lot of work in either Factor X or XIa in that space, but we were opportunistic in that area.

We feel very confident about the SSP data readout that will come next year. Our AFib readout will come as well. Recall, we had a very large 2,000-patient SSP study, Phase II that showed really significant relative risk reduction with minimal bleeds. And we did a lot of work to really get the dose right. You've also seen recently the announcement from Bayer. They have a positive study in SSP. And so that gives us more confidence in the mechanism.

The biggest opportunity really lies in atrial fibrillation. And a lot of work was done there with our partner, J&J. We took a similar playbook to what we did with Eliquis many years ago. We conducted over 1,000-patient TKR study that showed similar low bleeds, and we were very choiceful in the dose that we brought into that study. So when you look at the dose in SSP, which is 25 milligrams BID, we're actually looking at 100-milligram BID dose in atrial fibrillation. And with now over 20,000 patients enrolled in the study in a blinded fashion, we're not seeing anything remotely close to what Bayer had presented when their study was stopped. So we're excited for both of those data readouts next year.

Yes. And those are very large market opportunities. Is there -- do you want to turn the card over on those next year before you look at other potential indications? Or is there maybe a few other cardio indications that you can go after with milvexian?

Yes. We are in constant discussions with our J&J partners around what could be next. Obviously, we want to see positive studies in SSP and AFib, but there are a number of potential future indications that we could pursue together.

Yes, AFib for sure seems like a major, major -- more of an unmet need that really than any other cardio verticals I feel like?

It's exciting. You know we're leaders with Eliquis really over the last decade. The product is phenomenal, continuing to grow linearly just about every month. We're now at about a 75% NBRx share in the U.S. And that said, there's still about 40% of patients that are either untreated or undertreated. And why is that? Because of risk of bleed. And that's what, hopefully, milvexian will bring to these patients and to the broader Afib population, a lower bleeding profile than the standard of care Eliquis with comparable efficacy.

Yes. So sticking with cardio, let's talk about Camzyos for a second. So the -- just with respect to new patient identification, are you past some of the initial investments and awareness? Are you looking more at the kind of access reimbursement type of -- like give us some -- a bit of a status update on the commercial and what's the drivers from here?

Yes. As David mentioned, when you look at Camzyos, it's another one of our key growth drivers that's annualizing now at over $1 billion, and we expect to see continued significant growth from this important product. So we launched the product several years ago. It was a product with the REMS program. It took some time for our centers of excellence to kind of operationalize a new program, understand a new treatment modality.

But when you look at the performance of this brand growing at very high double-digit rates with durations of treatment now at almost 4 years, we expect, you're going to see really significant growth. And I still think we're scratching the surface because we've got about 20,000 patients, a little over 20,000 patients on Camzyos today. And we know there are still about 70,000 patients with obstructive HCM that are diagnosed and waiting for Camzyos. And that doesn't even include these hundreds of thousands of patients who are out there who are undiagnosed.

And so our focus is continuing to drive growth in the centers of excellence. And what I'm also pleased about is what we're seeing in the community cardiology offices. As now we have more time behind us, we're seeing uptake coming from the community card -- community cardiologists in the U.S., which is also driving nice growth for the brand.

Is the speed of diagnosis and as docs become more familiar with sort of the symptom the presentation, is that getting better? Is that accelerating? And maybe talk about that in the context of maybe the OUS opportunity?

Yes. So we've definitely seen an increase in diagnosis rates over the last couple of years. I think the direct-to-consumer campaign certainly helps patients. When you look at a disease that is so heavily misdiagnosed or going undiagnosed, there are so many patients out there who are suffering who can look to direct-to-consumer and say, "Hey, that's me. That's something that I may be suffering with. I'm going to go ask your doctor. And that's what we've seen. We've seen that coupled with a shift since we've launched into NYHA Class II, which is a little bit less severe than what we see in Class III and Class IV.

And so we're seeing that shift come into the U.S. today. We're now continuing to start outside of the U.S. in launching, getting reimbursement, and we're finding very similar successes in a number of our major markets. So very pleased with what we're seeing with Camzyos, and this is going to be a very big product for the company.

And that's another area that we were talking about AI earlier. One of the challenges that we had is the cath labs were full. They're back to back with patients and getting patients in to get them properly diagnosed now that there's a treatment option was one of the barriers that we had early on. One of the things that we did is we used AI to go back, working with some of the centers of excellence using AI to review the echocardiograms of these patients and then with about 90% accuracy, identifying those patients that had cardiomyopathies. So with that, that helped the doctors appropriately identify the patients to bring in to provide treatment. So that's just another area where AI is adding value to the health care system.

Is that something that you have to go through FDA to sort of as a diagnostic tool or is it just sort of analytics that you can put in your thought?

It's an analytic -- it's a tool that the cardiovascular doctor uses at the end of the day to determine it.

Okay. Okay. So Sotyktu, another new product launch. So maybe same kind of question there, like give us some of the go forward, what are the pushes and pulls as you look to '26?

Yes. So as we came into '25, certainly, we were not where we had hoped we would be. But it was an important year coming in because we finally were able to secure access that was at parity to Otezla. And so we continue to see improvements in new patient starts in TRxs. However, it's just not where we expected we would be when we launched this product. We made the difficult decision to cease promotion in dermatology in the U.S. and in a number of our ex-U.S. markets because really the lack of competitiveness in there.

And this is an area that requires significant investment, and we want to make sure that we're leveraging our capital in the best way possible, investing behind what we see our key growth drivers like Cobenfy, like Camzyos and also investing into R&D and/or dropping to the bottom line. What we're excited about, though, is some of our next set of data readouts. We'll have a data readout in SLE for Sotyktu coming into 2026, which is really exciting. As you know, that has been a very, very difficult area to have success with medications.

We conducted a Phase II study there, if you recall, and we saw really exciting results, and we're hopeful to see a positive study there. And then that, as you know, are treated by rheumatologists. So with an SLE readout and then in 2027, we'll have a Sjogren's readout, which are areas of really high unmet need and areas where we believe that we can win with Sotyktu.

Okay. That makes sense. And then maybe in the final few minutes, I know, David, we talked at the beginning of this year, health care policy was a topic du jour. We've had some great insights with Secretary Azar yesterday and then Marty on Tuesday. Talk a little bit about where Bristol is with regard to the rest of the industry on the tariff, MFN. I know you guys have already communicated that you're onshoring a lot of manufacturing and so bringing jobs over here. But maybe talk through kind of where you are in that continuum.

Yes. Look, we continue to engage with the administration, but as well as policymakers broadly. And a couple of things I'd say around this is, one, we feel we're really good where we are from a tariff perspective. We have a very flexible supply chain, as you highlighted. We're continuing to increase our investments within the U.S. in order to make it very flexible, both in Massachusetts as well as our operations in New Jersey. And we're also doing a number of other things from engaging on an MFN perspective. We can't talk about those discussions, but we believe it's a critically important that access to medicines is given and also that the cost differential between outside the United States and inside the United States gets more normalized over time. So all of those types of things are really good.

On the tax policy side of things, that's critically important to incentivize investments here in the United States. And I think the recent changes of the one big beautiful bill, but as well as the top Tax Reduction and Jobs Act that happened earlier are all things that equalize tax policy globally that enabled us to move capital investment here into the United States. So all of those things, we feel really good about, and we're going to continue to engage on that.

The last thing I would say is on -- as far as on the FDA side of things, we really haven't seen any impact in our engagement in the products that we have going through the regulatory process. The people at the FDA have just been fantastic, and we're moving at pace as we have been. So we haven't seen any impact there either.

One element to come out of that is there this year, it does seem like there is a much more consumer-driven kind of model that's coming out of pharma and big cap biotech. Maybe talk about that as a strategy for Bristol. You have a lot of companies that now have portals that you can go right into. But I think it just sort of connects a lot of payers and patients, but some are more than that, right? Some are more of a drop ship kind of element. I don't know, but where does that rank in terms of Bristol's sort of distribution and priority?

This is an area where we are completely aligned with the administration. We think direct-to-patient is very important. The ability to have improved visibility into drug prices, ensuring access and affordability. We were one of the first companies to announce that Eliquis would be available through direct to patient through Eliquis 360 at a price that is a 40% reduction from our list price. So patients who either were cash-paying patients or underinsured patients could go to the pharmacy and get this at a significantly reduced cost.

We then follow that up with Sotyktu. And so patients now can go and get Sotyktu at a roughly 80% reduction than they would pay at the pharmacy counter. So we think this is really important, and it's a trend that we know will continue with this administration and I think beyond.

Awesome. David, Adam, thank you very much.

Thank you.

Thank you, Geoff.

Welcome to the Bristol-Myers Squibb Third Quarter 2025 Earnings Conference Call. [Operator Instructions] 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 third quarter 2025 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 we welcome Cristian Massacesi, our recently appointed 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 2024, and sales growth rates will be discussed on an underlying basis, which excludes the impact of foreign exchange. All references to our P&L are on a non-GAAP basis.

And with that, I'll hand it over to Chris.

Thanks, Chuck. Welcome, and thank you for joining our third quarter earnings call. Q3 was another strong quarter, reflecting focused execution across the business as we continue to make progress on our plan to position Bristol-Myers Squibb for long-term sustainable growth. Building on the momentum from the first half of the year, we saw continued strong demand across our Growth Portfolio, achieved positive clinical and regulatory milestones and further aligned our cost structure with the needs of our business.

Let me start with a high-level review of our quarterly performance on Slide 4. Our growth portfolio delivered another strong quarter with sales increasing 17% year-over-year, strengthening the foundation we're building with assets that are early in their life cycle. Growth was driven by multiple products including our IO portfolio, Reblozyl, Camzyos and Breyanzi. And due to our strong performance to date, we are again raising our top line guidance and maintaining the midpoint of our bottom line guidance. David will provide more detail shortly.

Our two recent launches performed well in Q3. Cobenfy is delivering steady growth as we continue to receive positive feedback from physicians on key indicators, supporting our expectation that this is a meaningful first indication for Cobenfy. Qvantig's launch is also tracking well.

From a clinical and regulatory standpoint, I want to highlight a few recent updates. On the clinical data side, in our protein degradation platform, the Phase III EXCALIBER study for iberdomide in patients with relapsed or refractory multiple myeloma demonstrated a statistically significant improvement in MRD negativity rates. Now that we have these results in hand, we will be discussing these compelling data and potential paths forward with health authorities. The trial will continue to evaluate PFS, which is expected in 2026.

CELMoD have the promise to be a new foundation in the treatment of hematological malignancies. More broadly, our multipronged protein degradation platform has the opportunity to also address solid tumors, initially with our oral androgen receptor ligand-directed degrader, among others.

At the World One conference last month, we presented Phase II data for pumitamig with our partners at BioNTech. The clinical development program is both advancing and broadening for this important asset. Last month, we initiated the pivotal triple-negative breast cancer study and plan to share early data at the San Antonio Breast Cancer Symposium in December. Additionally, pivotal studies for pumitamig and chemotherapy combinations are now initiating in first-line microsatellite stable colorectal cancer and first-line gastric cancer.

This week, we announced encouraging data at the American College of Rheumatology Convergence Conference, which continue to strengthen our conviction behind CD19 NEX-T in autoimmune diseases and Sotyktu in rheumatology. We presented additional follow-up data for CD19 NEX-T in both lupus and scleroderma, have presented the first disclosure of data in myositis. For Sotyktu, the long-term extension data from the Phase II PAISLEY study continues to validate its potential in lupus as we look forward to Phase III results.

On the regulatory side, we achieved several milestones, which include our potential first-in-class bispecific ADC iza-bren receiving Breakthrough Therapy Designation for previously treated advanced EGFR-mutated non-small cell lung cancer. And earlier this month, the FDA granted Fast Track Designation to our anti-tau antibody for the treatment of Alzheimer's disease currently in a Phase II study with data expected to read out in 2027.

Together, these milestones highlight the potential of our pipeline to both enhance and sustain growth in the outer years by addressing critical areas of unmet need and the importance of advancing these programs quickly and efficiently.

On the business development front, we recently announced we are acquiring Orbital Therapeutics to strengthen our cell therapy franchise where we have industry-leading expertise. This acquisition will add a potential off-the-shelf best-in-class asset, OTX-201, which can be administered in the community setting. This in vivo CAR T represents a novel treatment approach that could redefine how we treat autoimmune diseases. We will also gain access to Orbital's differentiated RNA technology platform, which combines various RNA engineering and advanced delivery methods.

In addition, we saw progress with our partner, SystImmune, as we announced that the first patient was treated in the global Phase II/III trial of iza-bren in previously untreated triple-negative breast cancer ineligible for anti-PD-L1 drugs. In August, we closed the previously announced licensing agreement with Philochem for exclusive worldwide rights to OncoACP3, potential best-in-class radiopharmaceutical therapeutic and diagnostic agent with the opportunity to become a breakthrough treatment for prostate cancer.

We continue to be excited about the overall opportunity with radiopharmaceuticals and believe Philochem added to Rayze, offer a transformational platform for cancer treatment.

In terms of progress, we opened a U.S. manufacturing hub with the ability to deliver Rayze's next-generation radiopharmaceutical therapies directly to patients within just 3 days of production, a critical advantage due to the short shelf life of RPTs. The facility is currently manufacturing clinical doses of Rayze 101, which is in Phase III clinical trials for GEP-NETs.

Moving on to key data catalysts on Slide 5. As we've said before, we are entering a data-rich period. We continue to anticipate data readout for ADEPT-2 by the end of this year and have two additional Cobenfy studies in Alzheimer's disease psychosis, both of which are expected to read out next year. We anticipate needing 2 of these 3 studies to read out positively to support regulatory approval.

The pace of pivotal readouts will accelerate in 2026. As a reminder, over the next 12 to 24 months alone, we expect data for 7 new molecular entities and 7 meaningful life cycle management opportunities. Among others, we will see data for admilparant and IPF, a fatal lung disease with high unmet need; CELMoD, iberdomide and mezigdomide, which represent a significant step forward in the treatment of multiple myeloma; the broad milvexian program, where we are running 3 large Phase III trials to address ongoing unmet needs for patients with cardiovascular disease, including an AFIB trial that could potentially open treatment to at least the 40% of AFIB patients not suitable for Factor Xas today; Cobenfy and a broad range of Alzheimer's related neuropsychiatric conditions; and Sotyktu in lupus and Sjögren's.

Together, these represent an attractive set of near-term catalysts that can further shape our pipeline and longer-term growth trajectory given the significant commercial potential of the indications. And looking out a bit further, by the end of this decade, we have the potential to introduce 10 new medicines to the market and at least 30 significant life cycle management opportunities. This strategy is designed to set BMS on a clear path of strong and sustainable growth, which remains our guiding principle.

Beyond the specific commercial and R&D highlights, the company continues to focus on strong financial discipline. Consistent with prior quarters, while we generated significant cash flow in the third quarter, we also continue to be prudent in managing our expenses as we align our cost structure with the projected shape of our business. In addition, we progressed our efforts in the quarter to rewire how we operate, including continuing to integrate digital technology and AI across the company. We anticipate these efforts will drive additional efficiencies going forward and significantly enhance the agility of the organization.

So what does this mean? Between our Growth Portfolio performance, the business development activity I just referenced, including the BioNTech partnership and combined with our broad pipeline and strong financial discipline, we feel even better about our longer-term growth potential. I want to take a moment and thank my colleagues around the globe who are committed to our mission to discover, develop and deliver innovative and life-changing medicines to patients.

With that, I'll turn it over to David.

Thank you, Chris, and good morning, everyone. I'm pleased to report another strong quarter of execution. The Growth Portfolio continues to perform well and we continue to maintain cost discipline.

Now turning to the third quarter sales performance on Slide 7. Total company sales were approximately $12.2 billion, which reflects strong demand across our business. Global sales of the Growth Portfolio increased 17%, driven primarily by demand across multiple brands, notably our I/O portfolio: Reblozyl, Camzyos and Breyanzi.

Beginning with a review of the oncology portfolio on Slide 8. Opdivo global sales were approximately $2.5 billion, up 6%, driven primarily by continued demand. In the U.S., sales grew 6% to roughly $1.5 billion, largely driven by a strong launch in MSI high colorectal cancer and continued share growth in first-line non-small cell lung cancer. This growth was achieved even as we saw expanded uptake of.

Outside the U.S., sales grew 6%, driven by demand with expanded indications across multiple markets. We are pleased with the expanded growth of Qvantig with sales of $67 million in the quarter. Growth was fueled by continued use Qvantig across all indicated tumor types as well as the permanent J code received in the quarter. Due to the strong performance year-to-date, we now expect global Opdivo sales together with Qvantig to deliver stronger growth than previously guided, with sales expected to increase in the high single-digit to low double-digit range for the full year.

Turning to our hematology performance on Slide 9. Reblozyl's global sales were $615 million in the quarter, reflecting continued strength across our MDS-associated anemia indications. We're annualizing over $2 billion in sales for the brand. In the U.S., revenue growth continues to be strong, up 38%, primarily due to demand in first-line RS-positive and RS-negative setting as well as improved duration of therapy. Outside the U.S., Reblozyl sales grew 31%, driven by demand in newly launched markets.

Moving to Breyanzi. Sales were $359 million in the quarter and now annualizing over $1 billion. Global sales grew 58%, reflecting strong demand across all indications. In U.S., sales were $251 million, growing 45%, reflecting growth in large B-cell lymphoma and expansion from new indications approved last year. Outside the U.S., sales were $109 million, more than doubling due to continued strong demand across existing markets along with added demand from newly launched markets.

Transitioning to our cardiovascular performance on Slide 10, starting with Camzyos. Global sales increased 88% to $296 million, reflecting continued robust demand. This is another asset in our growth portfolio also now annualizing over $1 billion. In the U.S., sales were $238 million, up 76% driven primarily by increasing new patient starts. Outside the U.S., sales growth more than doubled driven by continued launch momentum in multiple markets. Eliquis global sales were $3.7 billion, growing 23%, primarily driven by continued strong demand and the expected favorable impact of Medicare Part D redesign, U.S. sales grew 29% and ex U.S. sales grew 11%.

Moving to immunology performance on Slide 11. Sotyktu sales grew 20% globally. In the U.S., sales remained consistent with prior year due to demand being offset by higher rebates associated with our increased commercial access.

Now turning to discuss Cobenfy on Slide 12. Cobenfy sales were $43 million in the quarter and $105 million year-to-date. As previously communicated, sales and weekly total prescriptions continue to grow steadily. We remain focused on disrupting the entrenched D2 prescribing behavior by educating physicians on Cobenfy's innovative profile and we've completed our field force expansion to increase reach and frequency to targeted health care professionals.

Now let's move to the P&L on Slide 13. Gross margin was approximately 73%, primarily due to product mix. As expected, operating expenses decreased by approximately $100 million to roughly $4.2 billion compared to the same period last year, primarily reflecting the savings from our ongoing strategic productivity initiative. Our effective tax rate in the quarter was 22.3%, reflecting our earnings mix. Overall, diluted earnings per share was $1.63 due to strong performance in the quarter and includes net charges of approximately $530 million or $0.20 per share attributed to acquired in-process R&D and licensing income primarily related to the Philochem asset license and SystImmune milestone payment.

Turning to the balance sheet and capital allocation highlights on Slide 14. Our financial position remains strong. We generated cash flow from operations of about $6.3 billion in the third quarter with nearly $17 billion in cash, cash equivalents and marketable securities as of September 30. Our capital allocation priorities remain unchanged as we continue to take a strategic and balanced approach.

As Chris mentioned, in recent months, we closed our license agreement with Philochem, announced the acquisition of Orbital Therapeutics and advanced our SystImmune in partnership. Strategically investing in our growth portfolio brands along with business development are our top priorities. We also continue to be on track to further delever our balance sheet. As of the end of the third quarter, we have paid $6.7 billion of the $10 billion debt paydown we've committed to by the first half of 2026. And we remain committed to returning capital to our shareholders through the dividend.

Now turning to our non-GAAP guidance on Slide 15. We are increasing our full year revenue guidance by $750 million at the midpoint to a range of $47.5 billion to $48 billion, primarily reflecting continued strong performance of our Growth Portfolio. We continue to expect the Legacy Portfolio to decline approximately 15% to 17% for the year, and our Revlimid sales expectation remain at approximately $3 billion, along with the continued impacts from generics of Pomalyst in Europe, Sprycel and Abraxane.

Our gross margin guidance for the year remains unchanged at approximately 72%, and our operating expense guidance also remains unchanged at approximately $16.5 billion, reflecting over $1 billion in net savings versus 2024. Regarding OI&E, we now expect annual income of approximately $500 million due to higher-than-anticipated royalties, ,licensing income and favorable interest income. We are maintaining our full year tax guidance of approximately 18%.

As a result of our strong performance year-to-date, the midpoint of our revised 2025 non-GAAP guidance would have increased by approximately $0.20 per share. This increase was offset by the net impact of acquired in-process R&D charges and licensing income, primarily related to Philochem asset license and a SystImmune milestone payment. As a result, we are narrowing our expected EPS range for 2025 to be between $6.40 and $6.60, which leaves the midpoint of our range unchanged.

Taken all together, I'm pleased with the performance of the business year-to-date, and I'd like to thank our colleagues around the world for their continued focus and execution.

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

Thanks, David. And before we start our Q&A session, I want to note that questions related to our solid tumor development programs will be answered by Adam rather than Cristian during today's call.

And with that, Betsy, could you please poll for questions?

[Operator Instructions] The first question today comes from Chris Schott with JPMorgan.

Just I wanted to start with ADEPT-2. Is there any additional updates you can give us in terms of any actions, if any, that you've taken following some of the clinical site reviews you highlighted on the 2Q earnings?

And then maybe just putting the broader ADEPT program into context, as we think about ADEPT-1 and 4 next year, can you just talk about the relative confidence you have in those studies relative to ADEPT-2 just given some of the differences in study designs? Just maybe just an update kind of broadly on how you're thinking about that indication.

Sure. Thanks for the question, Chris. Maybe I'll start and then obviously, Cristian can chime in with any additional context he has. So just remember, ADEPT-2 is obviously an ongoing study. And it's an ongoing study, as I referenced in my prepared remarks, that has a readout in the next 2 months. So we're not going to be able to provide a lot of specific comments on the product.

But what I can say are a few things. First, I will reiterate that we expect results by the end of the year. And of course, we'll communicate those results as we normally do. The second thing I would say, which really gets to the second part of your question is while we remain blinded to the data, our confidence in the Cobenfy development program including an ADP continues to be strong. And with respect to ADP, I'd just remind you of the source of that confidence. We obviously have compelling external data going back to the Lilly day in the late 90s. We're hearing very interesting real-world stories based on our experience, albeit at schizophrenia. And of course, we have internal data with respect to the ADEPT-1 lead-in and the ADEPT-3 extension data.

So that's what I would say about Adept-2. But if I step back from the specific studies, remember, the work that we're doing in development fits with the focus that we have on execution really across the company. And given the importance of the late-stage studies, I think it's prudent that we take whatever learnings we can and pull whatever appropriate levers we can to ensure that we deliver these studies with the highest PTS and on time. We're obviously excited to have Cristian on board to bring a fresh perspective to that.

So net-net, I feel good about where we are in terms of working through the broader development programs and ensuring that we're executing appropriately. But Cristian, I don't know if you want to add anything.

Thanks, Chris. Yes, let me try to, first of all, reassure that the Cobenfy's development program is progressing really at a rapid pace. We currently have in the development plan 14 studies that are ongoing or in the process to be activated. Ten of those studies are pivotal studies. We actually posted and maybe have seen a [ study ] in bipolar mania.

We are also expanding the indications. We plan to initiate pivotal studies in autism spectrum irritability next year. So the program is moving at pace. I think, Chris, you answered very well the reason to believe. I want to add that you -- part of your question was some differences. Just to clarify, ADEPT-4 is very similar to ADEPT-2. It's the sister or the brother study. So we are doing the ADEPT-4 exactly in the same patient population with the same primary end point. Then ADEPT-2, as you know, is projected next year.

ADEPT-1 is slightly different because it's a relapse prevention design. This is a trial in which patients are rolling to Cobenfy for 12 weeks. And then at the end of that period, based on the response on the psychosis metrics and CGI, the patient is randomized to Cobenfy and placebo. So different approach but same setting.

The next question comes from Geoff Meacham with Citi.

Just have a couple also on Cobenfy, but more commercial. How would you guys characterize the speed of reimbursement and maybe the depth of prescribers in the U.S.? I guess I'm just looking for what could be a tipping point of demand as it sounds like maybe there's more work to do on education.

And then also I wanted to loop in Cristian here. I know obviously, early days. But can you give us a sense of your priorities and maybe approach to development for a diversified portfolio like Bristol?

Adam, then Cristian.

Yes, yes. Thanks for the question. So we're pleased with the progress that we've made in Cobenfy's first full year on the market, and we're establishing a new treatment paradigm and what we knew was going to be a highly entrenched market. As you have probably seen, we've now surpassed 2,400 TRxs on a weekly basis and we expect to see continued steady growth. We are adding a significant number of new trialists each week. Physician feedback continues to be positive regarding Cobenfy's profile, and we're very pleased with the kind of the pace of access that we're able to establish early on.

As you know and as a reminder, that this is a heavy Medicare/Medicaid population. And so we have virtually 100% access across both. Now stepping back, there's clearly more work to do in year 2. We need to continue to increase both breadth and depth of prescribing, which will drive additional growth for the brand. We've onboarded our expanded field force now in the community and in the hospital setting. And so based on the leading indicators that we're seeing, Cobenfy is going to deliver continued steady growth in schizophrenia. And longer-term growth is going to be fueled by additional indications as Cristian has stated, and that's what we've also seen with other psychotics in the market. But we are confident that Cobenfy will be a big drug over time. Cristian?

Yes. Geoff, thanks for the question. Let me tell you why I decided to join the BMS beyond the fact that I like Chris. The first thing is the science. BMS always did a very strong science and continue to do it. And of course, the portfolio, it's an impressive portfolio across the therapeutic areas with a lot of potential first-in-class and/or best-in-class assets. So this is, of course, the basis. I also like very much the focus that BMS is having in the therapeutic areas where it's playing because beyond oncology and hematology, the focus on immunology, cardiovascular, in neuroscience specifically, those are TAs where you have the intersection, the best intersection of what is the current or the emerging biology rationale and the medical need.

Of course, the BMS people has always been very highly reputated. I found a very strong development organization here. What I want to do here, what I'm starting to do and going to continue to do is evolve this drug development organization to try to deliver on the pipeline, the short and mid and long-term pipeline, focus on the key strategic priority. I have three main areas where I started to work and will continue to work. The first thing is how we prioritize our ongoing and future opportunities. Usually, it's a science -- strong science needs to be the basis. So we do execution, flawless execution is incredibly important in development and add value. Because what we need -- what we do needs to bring value to the patients and, of course, to the company.

The other aspects I'm starting to work with a lot of urgency is integrating new way of working in development. We are at turning point. We cannot continue to do things like what we're doing in the last decades. We have AI. We have a novel solution and tools, and this needs urgently integrating the way we work. The last thing is people. I need to continue to build the right teams and attract talent in the company.

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

I wanted to touch on the competitive landscape for the PD-L1 VEGF bispecifics. So we saw some data at ESMO with PFS benefit in the HARMONY 6 trial in squamous non-small cell lung cancer. Can you just help frame how that maybe informs how you're thinking about your partnership with BioNTech? Does it make you more incrementally confident? Or is it really too early to read into kind of your program? .

Thanks, Evan. Let me just say one thing about BioNTech and then I'll turn it over to Adam. That partnership continues to go very well. We have a very tight relationship with BioNTech both on the development side and, of course, anticipating the commercial opportunity on the commercial side. And so far, that relationship is quite strong. But Adam, do you want to go through the details?

Sure. Thanks, Chris. And Evan, so we believe that pumitamig has the potential to become a new standard of care. The data that we have seen both from BioNTech as well as from the competitors add to our conviction and broad development program that we have for pumitamig. We have multiple trials that are currently ongoing across several solid tumor indications. As you know, we've got first-line non-small cell lung cancer. We just presented data in small cell lung cancer. And we also have triple-negative breast cancer first-line initiating. We will be presenting TNBC data at San Antonio Breast in December.

We've also been working with urgency with our BioNTech partners and made very good progress building a robust clinical development program. In fact, we'll be initiating two new studies that are now posted on clinicaltrials.gov in first-line MSS CRC. And as you know, that's not a place where first-generation PD-1, PD-L1s have shown activity as well as in first-line gastric cancer. So our focus is on speed to market. Our opportunity is to be either first or second to market across indications. And we feel very good about combining our industry-leading commercial and operational capabilities with BioNTech's scientific expertise. And we plan to maximize the potential of this asset.

The next question comes from David Amsellem with Piper Sandler.

So I wanted to come back to Cobenfy. And not trying to read too much into the prescription data over the summer relative to earlier this year, but I didn't want to ask about how you're thinking about potential or key barriers to adoption thus far? Is it GI tolerability? Is it twice daily dosing? Is it just prescriber inertia in terms of the dominance of the D2 blockers? Just wanted to get a better sense of what you're hearing and seeing in the field and what you think you need to do to drive more acceptance of product among psychiatrists.

Thanks for the question, David. I'll turn it to Adam. But one thing -- I just was in the field on with Cobenfy sales reps very recently. And what I would say is that once physicians begin to use these products and patients have access to it, one thing that gives us a lot of confidence about the long-term potential of this product in schizophrenia is the feedback that we're getting from both. Feedback continues to be very strong. But I'll let Adam go through the specifics around your question.

Yes, David, I appreciate the question. So as I said earlier, we're pleased with the progress that we've made. We're now just about a little over 1 year in the market right now. And this is an entrenched market. This is the first new mechanism that's been approved in over 3 decades in the space. And so I think what's really important, what we look for in terms of leading indicators are adding new trialists. And we're tracking very well on a weekly basis as well as new prescriptions. When we look at the feedback in general, the feedback is very positive regarding Cobenfy's profile, as Chris mentioned.

I would say that the #1 question that we get as a team is around how to switch from a D2 to Cobenfy. And even from physicians who are sitting on the sidelines, that's the question they want to know. And so we've got robust peer-to-peer activities that are ongoing. We've introduced real-world data and we have a Phase IV switch study that reads out early next year. All will help build physician confidence. What I'll say is if you look historically all the recently launched D2s, we are tracking ahead of all recently launched analogs in schizophrenia. So based on everything that we're seeing, we feel good about the performance for Cobenfy. We're going to continue to see steady growth and the inflection will come as we continue to add new indications.

The next question comes from Asad Haider with Goldman Sachs. .

Just first for Chris or David, on the cost side, as it relates to your strategic productivity initiatives where another $1 billion in cost savings is expected to drop to the bottom line by 2027, any updated thoughts on the shape of this over the next couple of years in the context of the potential R&D expenses associated with the development of BNT-327 as it starts to go forward into later-stage Phase III programs? Recognizing, of course, that you have other Phase III programs over the next 18 to 24 months are going to come off. Just trying to understand the margin trajectory as we go through these pushes and pulls. .

And then second for Cristian. Maybe just double clicking on your previous response. Could you share with us any early thoughts on the pipeline and if there are programs that you're particularly encouraged by?

Maybe I'll start and turn it to David for the first question, and then Cristian, you can pick up the second question. Just on the cost side, as David goes through some of the specifics, the one thing I would just remind everyone is that the way we think about costs and our investment profile generally is there's a balance that's going to be maintained.

One is continuing to invest in areas to drive value and growth. That's not only on the pipeline, including B&T but the R&D organization more generally. And then, of course, as we did this past few quarters, investing in the growth profile of the company with Adam's organization. At the same time, we have committed, and I think you've seen it in the numbers over the last number of quarters, is we're going to be disciplined with respect to financial management. And that's going to be our operating approach going forward. David?

Yes. Asad, I know '26 is top of mind for many folks. And so let me just share with you how I'm thinking about it overall. First, we're exiting 2025 with really strong performance from our Growth Portfolio. Year-to-date, it's up 16%. And as I said in the prepared remarks, we now have 4 products that are annualizing greater than $1 billion in that growth portfolio. So we're exiting this year in really good shape as we head into next year.

We're also executing well against our efficiency commitments. We're on track for $1 billion this year, and we have clear line of sight to the $2 billion that we're targeting by 2027. So feel good about that as well.

And also remember, we have numerous Phase III programs completing next year and going into 2027. And just as a reference point, our 2024 cost base was $17.8 billion and we're guiding $16.5 billion this year. So we made really good progress. And I'd say, overall, we have a clear line of sight to the pushes and pulls at '26, and I feel confident in our ability to manage the cost base. And as Chris said, what we're doing, we're focused on balancing up investments that we need to do in order to drive growth in the Growth Portfolio as well as to create headroom for additional business development. And we'll balance that with our savings program.

And look, we're getting smarter as we go when we see additional opportunities. So we have a lot of P&L flexibility and we're going to remain financially disciplined as we go through this transition period. And this financial discipline not only helps us manage our margins, but it also provides a strong basis to deliver cash flows to strengthen the balance sheet as we committed to, provide both strategic and financial flexibility and continue to build on the growth portfolio.

Cristian?

That's okay. Chuck, I can speak lengthy. Asad, thank you for the question. I mean, I cannot speak about solid tumors and oncology, but there are a lot of exciting readout and asset in the portfolio. I think we talked about Cobenfy and how invested we are on this drug and how excited we are because there are multiple readouts. I want to speak on two short term potential readouts.

One is milvexian. When I digged into milvexian, I think BMS, first of all, has a deep expertise and understanding of this area, this market, cardiovascular. This is an oral next-generation Factor XIa anticoagulant and can be the first maybe and the only Factor XIa in atrial fibrillation and ACS and potentially best-in-class in SSP. So I'm really eager to see the readout of these studies. ACS and SSP are planned next year, and we are really pleased that we can complete atrial fibrillation study next year.

The other drug I want to point out is admilparant because admilparant is playing in a very difficult disease, pulmonary fibrosis. That is a huge medical need, and Chris mentioned that. I think we have very strong proof of concept in both IPF and PPF because the Phase II study that is underneath the registrational programs show more than 60% improvement in lung function decline. I think this is give us a lot of confidence on the 2 pivotal studies, and very eager to see the FPF1 and the dynamics here.

Now let me talk a little bit about the platform because this is a short term and more on the midterm, I'm really, really excited in what are some of the scientific platform this company can leverage. One is the protein degradation. BMS is a leader in this space, think Revlimid, Pomalyst. And I think today, targeted protein degradation is one of the priority research platforms across the TAs. In our portfolio, if you scrutinize a bit every stage, Phase III, II and I, we have more than 10 in clinic that are protein degraders. And what excites me most is not that we just have a platform with preliminary data. Now we have Phase III data. Iberdomide met the primary point in relapse refractory myeloma for MRD negativity rate. And of course, we release that. And this is the first readout of why driving this platform give us confidence.

The other one I want to mention because I think it's very relevant is the platform that we are putting together in cell therapy for autoimmune diseases. We have an autologous CD19 CAR T. We presented the data in CR a few days ago, a preliminary data, spectacular data across indication, lupus, and myositis. And we have also a CD19 allogeneic CAR T in this space that is in clinic. It can represent an of-the-shelf option. And we acquired Orbital now that give us the in vivo platform that can be transformative in this space for multiple reasons. So this is great if you think, because it's, first of all, a step forward in the concept of immune reset and potentially to cure more patients with the autoimmune diseases, and BMS can only space. This is very exciting here. .

The next question comes from Mohit Bansal with Wells Fargo. .

My question is regarding the VEGF PD1 and the data we have seen from summit so far. So what is your impression of the data, especially on the OS side of things? And the second part of the question is that, I mean, there are two ways to think about it. One is like you could actually go after indications where PD-1s work really well or you could go after indications where VEGF work well and PD-1 could add some value there. Is there an either/or approach here? Or could there be a scenario where it works better to improve the efficacy of VEGF with the VEGF PD-1 approach? How do you think about that?

Adam? .

Yes, Mohit, thanks for the question. So in terms of what we have seen, we are encouraged by the magnitude and consistency of the PFS data that we believe will ultimately translate into a survival benefit over time. So the data we've seen adds to our conviction of the broad development plan that we're building. I do think in terms of the strategy that we have employed, as you can see, our strategy really is twofold. One is to become the new standard of care. For example, when you look at the studies we have in first-line non-small cell lung cancer versus standard of care as well as in small cell lung cancer, but also a good example of expanding beyond where PD-1, PD-L1s play. And that's in MSS CRC. And so that's the balance that we are taking as it relates to the strategy for pumitamig.

The other exciting factor that we have across both of our companies is the ability to combine pumitamig with novel combinations. So we've got a host of novel combinations, ADCs, targeted treatments, et cetera, that both companies we'll look to employ as quickly as possible. And we very much look forward to sharing these additional studies as they're ready to be posted online in clinicaltrials.gov.

Next question comes from Tim Anderson with Bank of America.

A couple of questions. The first is on trough earnings. Chris, are you still looking at very late 2020s relative to what you've made been forecasting, say, a year ago? Is that trending towards being pulled forward or being pushed back or maybe staying the same? We've seen lots of developments both at Bristol and then industry wide, and I'm wondering if any of that has changed the timing of reaching trough earnings.

And then just on Cobenfy, as you undoubtedly know, there's heightened investor nervousness around ADEPT-2 on the back of comments that were made in Q2. Do you think investors read too much into those comments that Samit has made?

So first of all, Tim, before I answer the questions, I just want to say congratulations on your next move. We're going to miss you on the calls and we won't take it personally.

With respect to trough, as you know and as we've discussed previously, we have not given long-term guidance just as a standard, of course, and that applies obviously to how we're thinking about the specifics of the trough. What I will say is that there's a consistency in what our focus has been. We continue to be focused on making this trough as shallow and as short as possible. We still anticipate that we're going to be exiting this decade with growth. Our North Star continues to be that we're going to grow as quickly as possible in order to maximize that exit trajectory, and we're doing the things necessary to enable us to do that.

You see the performance that we delivered on the commercial side. Obviously, that provides a very good foundation for how we think about our ability to navigate through the trough and exit with robust growth. Cristian has commented on the strength of our late-stage pipeline. We've got to continue to deliver that. And clearly, it's going to be important that we continue to maintain financial flexibility so that if we find additional substrate that makes sense for us to be the owner of, that we can engage either in partnerships or business development as appropriate. And that's generally how we're continuing to think about the trough.

With respect to the comments last quarter and this quarter, look, what I can say is that there's a lot of focus on execution of the company. There's a lot of focus on ensuring that we continue to deliver on that pipeline. We obviously understand there's a lot of focus on individual programs, including the ones that are going to be reading out most near term and that would include the ADEPT programs. So I wouldn't read too much into it other than to say that there's a lot of focus on us being able to deliver on each of the stages of our strategy, commercial execution. I think we feel really good about what we delivered this quarter, the strength of the late-stage pipeline and executing that and we've talked about that. And then also continuing to deliver strong financials with disciplined cost management. And we've done that, too. So feel good about where we are.

The next question comes from Luisa Hector with Berenberg. .

Maybe a policy question. I just wondered whether we should be worried about the lack of any subsequent deals with the administration. Is there perhaps a bandwidth issue? Just trying to -- you're in the queue waiting your turn to negotiate.

And then maybe just sort of expand that a little bit on to potential DTC offerings. You already have Eliquis, Anything you can comment in terms of that going live? Any impact on on volumes? And then perhaps just a mention of that guidance that you have for Eliquis for '26 and '27. How confident are you? Can you tighten those ranges at all now that we're sort of through '25, you've seen the Part D restructure impact and the DTC? So some of those changes there, how they're informing your view of Eliquis as we go forward.

Thanks for the question, Luisa. Maybe I'll start, and then I'll flip it over to Adam. Look, obviously, the policy environment remains very dynamic, both from a U.S. and an ex U.S. perspective, for that matter. I don't know that I'd read too much into no additional deals over the last week or so. What I would say from a BMS standpoint is we continue to actively engage with the administration. I would characterize those discussions as frequent. And while not always fully aligned, they're always constructive and thought-provoking on both sides. Clearly, tariffs are front and center, but we continue to monitor a host of other issues, including the shutdown and what potential impact that could have downstream. And then there's, of course, a lot going on ex U.S.

Framing all of that for us, though, is that -- we agree with the President on the need for equalization of prices. U.S. prices need to come down. We're sharing ideas to do that. Ex U.S. prices need to come up. We've seen some good progress, for example, in the U.K., but more needs to be done. And accomplishing those objectives while preserving the ecosystem for innovation that we have in the U.S. is what we're focused on. So there's a lot going on. It's manageable. We have a great team in D.C. of whom I'm incredibly proud, and we're engaging at the right levels. I'll let Adam handle the DTC questions.

Yes, Luisa, thanks. So as far as the direct-to-patient program, as you know, as part of our commitment to increasing patient access, we, with our Pfizer partners for Eliquis, we announced that Eliquis would be available via direct to patient at a discounted rate, over 40% less than the list price. I can say since launching the program, we have received a substantial number of inquiries through Eliquis 360.

If you remember, we also subsequently announced the Sotyktu will be available via our own direct-to-patient platform at a greater than 80% discount effective January 1. So we're launching this as part of our commitment to patient access and affordability. As Chris mentioned, we're listening, we're coming forward with solutions, and we're doing that with urgency.

As it relates to Part D redesign, for Eliquis, we are seeing a more even distribution of sales like we talked about throughout this year. We expect to see similar in the Q4 time frame as the coverage gap has been removed. And that is being offset by patients in the catastrophic phase for products like Revlimid, Pomalyst and Camzyos, for example. So when you look on a net basis, we're roughly equal in terms of the positives and the negatives.

The next question comes from David Risinger with Leerink Partners.

Yes. Congrats on the strong third quarter results. So I have two questions, please. First, milvexian is being dosed at 25 milligrams BID in secondary stroke prevention, which is the same daily dose as Bayer's Asundexian 50 milligrams QD. So could you please discuss milvexian's profile including its potency relative to Asundexian and comment on Asundexian's secondary stroke prevention Phase III trial readout in coming months. and implications for milvexian's secondary stroke prevention readout in the second half of '26.

And then my separate question is, are IRA prices for the first 10 price-controlled drugs in 2026, including Eliquis, currently being renegotiated?

So I will ask Cristian to start and then, Adam, you can briefly comment on the second question.

So let me start with your first part of the question relating to the dose. We believe that we characterized very well the dose, not only the scheduling, the dose and the design of the trial that we are running. Specifically on your question on the dosing, don't forget that we have a BID administration. And BID administration can actually ensure a better coverage of exposure that you need to get what you want to get. So this is, we believe, is an important differentiation so vis-a-vis what maybe other competitive drug can be using. So we are very confident. This is a work that has been scrutinized very carefully in BMS and, of course, with our partner, J&J, in this setting.

Let me tell about your second part of the question. I don't want to speculate on future competitive program results. But of all, a positive competitive SSP trial can be great for patients and validates the Factor XIa mechanism in this space. I am confident that our Phase III program that has been developed, as I say, with scrutiny, can maximize the efficacy milvexian and potentially can provide even a superior profile in SSP. And don't forget that the NAF and the ACS and milvexian is the potentially only Factor XI that can play in this indication. And these are, of course, very important part of the market.

I'll just add one thing. Cristian, thanks for the answer. We were able to, if you've seen clinicaltrials.gov, accelerate now the readout of atrial fibrillation for milvexian, which is the largest opportunity for the product. So now we expect all three studies to read out in 2026. As far as IRA, no, there was no plan to revisit Eliquis negotiation and that price will be effectuated January 1.

The next question comes from Carter Gould with Cantor.

I ask this question with an appreciation that your time lines have been consistent, but there's been lots of discussions around potential scenarios where you might add patients to sites that -- I'm talking about ADEPT-2, you might add patients to sites that underenrolled based. And can you address those discussions and say definitively whether you've gone back and added more patients since enrollment was completed based on your own ct.gov entries? And could that address the variance between what was implied by those time lines and the actual time lines to data?

Thanks for the question, Carter. And again, I appreciate there's a lot of interest in the study. All I can say is that we continue to expect the results by the end of the year. We're obviously going to communicate those results when they're available. And the good news is that it's practically November, so we don't have to wait long for the turning of that card.

The next question comes from Terence Flynn with Morgan Stanley.

Maybe just another policy, one. We've seen some headlines around these GLOBE and GUARD, what I assume are CMMI pilots for Medicare. Can you weigh in at all in terms of those, if there's any progress or give any details in terms of how those might play out?

And then a second question is just on iberdomide and your upcoming discussions with the FDA on a potential for a filing on MRD. What's your confidence level that FDA will actually move in that direction? Or do you think they're going to want to see more definitive data first before acting on MRD?

I'll hit the first one and then I'll ask Cristian to take the second. So on the CMMI potential demos, look, we've obviously seen the same coverage you've seen. I think it's too early to say really anything about what's in them, when they might read out and what the implications of that are. We're obviously actively monitoring and engaging, but nothing new to report there at the moment. And then Cristian, do you want to take the second piece of that on iber.

Yes. Iber showed this positive outcome in MRD negativity rate. We announced it. We are very pleased that the FDA keeps this very in consideration. There was a lot of discussion. It is an end point that, of course, we discussed and we agreed with the agency. We will share the data and we will discuss not only with FDA but with multiple regulatory agencies to see if this readout can grant or not an accelerated conditional approval. And we will keep you posted on the next steps.

The next question is from Courtney Breen with Bernstein.

Just one for me, particularly as we think about the PD-1 VEGF opportunity and the clinical development plan that you've alluded to here. What learnings are you taking from your first round in the PD-1 battle, the development and commercial kind of competition with Merck? What would you have done differently in that? And how are you using kind of a look back at that strategy to improve your approach in arguably a more complex and competitive environment?

Thanks for the question, Courtney. And I'll turn it over to Adam, but what I would just highlight is the first learning you can get is with the deal itself. The reality is based on the experience that we've seen in the first round of PD-1, PD-L1 competition, one of the things that's most clear is that the first and second players in that particular race have garnered the vast majority of the commercial value and the ability to help the most patients. And so our focus coming into this was that we wanted to make sure that if we were going to enter what could be a much more competitive space, that we were in a pull position. And so I think that's what we were able to do with the BioNTech deal.

But Adam, do you want to provide specifics?

Yes, Courtney, thanks for the question. Just a reminder, we're the only company to launch 3 I/O assets with Yervoy, Opdivo and Opdualag. So we understand what it takes to compete and win in a highly competitive market. We've got the infrastructure in place. We can leverage the capabilities that we built over the years. As Chris mentioned, order of entry clearly matters. We've seen that with PD-1, PD-L1s today. I would also say the importance of community oncologist is critically important. They are responsible for about 70% of the prescribing here in the United States and we've got decades-long relationships there.

Finally, I think the ability and agility to pivot quickly to support new implications is critical. So we've seen this velocity of launches in this first generation of IO with Opdivo now over 30 indications. And the final thing I'd mention in terms of learnings, I do think it's critically important to look at more novel, novel indications. We have seen over the last decade since Opdivo was introduced a host of new mechanisms and modalities that have been introduced to the marketplace that will continue to raise the bar on overall survival. So taken together, we're excited about the opportunity we have with pumitamig and our partnership with BioNTech. And our focus is to transform the current standard of care.

The next question comes from Akash Tewari with Jefferies.

Just on ADEPT-2. I think your team has hinted there are no cytorregularities that you're seeing right now and dropouts seem to be similar to the schizophrenia studies. So if that's the case, why hasn't the data been locked at this point? And why open more ex U.S. sites? And can you also comment specifically on what you learned from the open-label period in your relapse prevention studies with Cobenfy in Alzheimer's psychosis?

Yes. Again, I'm just going to reiterate what we said previously. The study is going to be reading out in the next couple of months and we're very close to that. So we're not going to provide additional comments on the specifics. I would also to step back though and remind you of what I said earlier, which is the confidence that we have in the overall Cobenfy program, which is what Cristian spoke to.

And then with respect to why we have so much confidence in the Alzheimer's disease psychosis program, I would just remind you of three things. First, we have compelling external data coming forward from previous studies. We have heard considerable feedback, albeit in the schizophrenia indication on the performance of the product on psychosis symptoms, which again gives us a lot of confidence albeit in a separate setting. And then, of course, we have additional data that we have internally. And so we feel good about where we are with the program at large. And obviously, we'll wait to see the ADEPT-2 data between now and the end of the year. And we'll report that out when we get it. Cristian, anything you would add?

Yes. I mean for ADEPT-1, as I said before, this is a relapse prevention design. So it's a different endpoint -- primary endpoint compared to 2 and 4. And of course, the study is ongoing. And we don't want to share data on the leading phase. This is -- we are putting the patient on Cobenfy for 12 weeks, and then we will assess the response with the same criteria for psychosis. And based on that, the patient will be randomized, of course, the patient is assessed certain degree of response to be randomized.

This is important because, of course, it's a learning -- that part of the study is open label, but of course, we will share the data in a moment which we will release the data.

Operator, if we can take our last question, and then I'll ask Chris to make some closing comments.

The last question today comes from Stephen Scala with TD Cowen.

I'm curious if you have concluded the IRA negotiations for Pomalyst and how did the results compare to expectations. GSK indicated yesterday that its negotiations concluded for one of its drugs, and they did not sound troubled in the least at the result of those negotiations. And I'll leave it to one question given that time is short.

Steve, Adam, why don't you take that? .

Steve, thanks for the question. Appreciate it. The IRA negotiations officially conclude tomorrow. And so we are currently finalizing that. There's not much I can say about the negotiation except for the fact that, as you know, the negotiation is for Pomalyst. And so Pomalyst, by the time the MSP is effectuated in January 27, Pomalyst will have lost exclusivity in the U.S. So again, we don't feel like this will have any impact on the company and the outlook of the company. And we believe that the price will be made public at the latest November 30. What we saw last year that it should come earlier. But taken together, we feel good about the negotiation and where we'll be at the end.

Thanks, Adam. And thanks, Chuck, also for choreographing today's call. We know it's a busy morning for all of you given that there are several companies in our sector that are going to be reporting. So I want to thank you all for joining the call this morning. .

In closing, our year-to-date results, I think, reflect the focus that we have on execution with strong performance from the growth portfolio, our business development activities that we spoke about during the call, continued progress on our strategic productivity initiatives and solid free cash flow generation. We're doing what we said we would do. We look forward to the clinical data readouts accelerating into 2026, which, as discussed, have the potential to, we believe, shape the potential of our pipeline and provide more certainty on the shape of our growth trajectory.

So again, thank you all for calling in today. And as always, the team is available for any follow-ups. So have a great rest of the day.

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

Thank you all so much for being here. And Lynelle, thank you so much for being here with us today. For those of you who don't know me, my name is Courtney Breen. I am the large-cap analyst here at Bernstein covering all of our U.S. names, Bristol included. And I am very, very proud and happy to share the stage today with Lynelle here from Bristol. She is the Head of the cell therapy business. And we're going to have a bit of a conversation around kind of particularly the potential in cell therapy, how it's landing in the hematology space, predominantly where it is today, where it might be going in the future.

And so really, really excited to talk about this because I think we've got some proof points now, but there's a lot of innovation on the horizon, which is really, really exciting. Perhaps before we dig into that, I'd love to hear, Lynelle, you just open with a couple of comments from your side. Anything you want to say to set the stage and set some context about your background and the conversation we're going to have.

Yes. Well, first of all, thank you, Courtney, and thank you for Bernstein for having me and BMS represented here today. And certainly, I'm excited to have a 40-minute conversation about cell therapy. I have passionately been involved in this particular business for 4 years. And I think to myself, when I go back when it all started for BMS, we embarked -- we were launching the very first CAR-T in multiple myeloma. We were going to be launching the third to market CD19 CAR-T, and there was a lot of unknowns. There was unknowns about how durable would these CAR-Ts be? Would they be successfully able to move up into earlier lines? What was the access and reimbursement landscape really going to look like? How are you going to be moving it into global markets? And could you scale and scale in a way that could allow you to have a marketplace that was very viable.

And so as we sit 4 years later, and I know after treating 13,000 patients, and we sit in a unique position as Bristol-Myers Squibb, where we have more manufactured clinical and translational data almost anyone else in this space. And it has afforded us the opportunity not only to grow our in-line assets, but it helps to accelerate our pipeline. And I think now when I sit here, we have near-term best-in-class, first-in-class CAR-Ts with our GPRC5D known as arlo-cel, our dual targeting CAR BCMA and GPRC5D in multiple myeloma as well as probably the asset you guys mostly asked us about, which is our CD19 NEX-T. And for obvious reasons, the field is really excited because they want to know, are these deep, durable treatment-free remissions with a onetime infusion, are they possible in diseases where functional cures were not even thought of 3 years ago.

And so we're really, really excited about the potential of what CAR-T can bring to the autoimmune space as well as neuroinflammatory. And so for us, we're super excited about cell therapy. We understand some of the challenges with cell therapy, but we do believe we're at a really important inflection point to bring the promise of cell therapy to more populations, more people as we continue to grow the class and move into other disease areas.

Fantastic. That is a perfect opening for where I wanted to start because I did really want to start on some of those market factors and kind of how the health care systems have potentially limited some of the use that perhaps if you look back 10 years, people were hoping to see by this point. There has begun to be enhanced utilization, but then we've also got bispecifics perhaps coming in and competing with the class as well in certain places.

As you look forward kind of 10 years into the future in the [ heme'd ] space, let's just kind of start there because there's many other places we can go. But in hematology, the next 10 years, what does good look like in terms of the potential for cell therapies? And what unlock are really important in terms of the health care system, be it access, be it kind of the way that the system works to ensure that these patients who need access can get access to these products.

I think it's always important to start with why has CAR-T not taken off like you see, for example, I spent a big part of my career in checkpoint inhibitors, the PD-1 space. And you would launch a new indication with the PD-1s in about 6 to 9 months, you were at peak class share, and you were anywhere between 60 and 70 depending on the actual indication, and it was pretty quick. But there was obviously factors in play there that are not in play for CAR-T because if you look at the efficacy and the transformational impact for patients, not too different than what you see with checkpoint inhibitors. You're giving people curative intent and the probably benefit of a CAR-T, it's a onetime infusion.

So you take somebody from being reminded that they are a patient with every dose, every swallow the pill, every tox, every side effect to being a person again after experiencing CAR-T. And so from that standpoint, what you really start unpacking is what are those limitations. And those limitations initially, everybody thought it was the manufacturers couldn't scale. And candidly, that was true, including BMS. But once the manufacturers were able to figure out how to move and automate in certain components as well as scale operationally, now we are unlimited in our ability to supply the marketplaces, including moving up into earlier lines. And so then you really started unveiling what were the real dynamics in play here that were limiting a CAR-T. And it's pretty simple when you really take a step back and look at it.

One is the CAR-Ts are not delivered in every community practice. And so most patients, 70% of them are treated in community practices around the United States. That dynamic is consistent in Germany. It also exists in Japan. Probably the one unique market is France, where CAR-T class is its highest in the world. It's at 40% CAR-T class is in France. And that's because it's an ecosystem that basically operates as one between community and academic center. And therefore, patients come into the fold to determine what is the best mode and modality of treatment and then they go get that treatment.

In the United States, patients -- most of the patients are initially diagnosed with their community medical oncologists. And it's at that time, will the community medical oncologists refer that patient to a CAR-T center or potentially reach to another modality that's available to them. And this is where TCs have certainly put pressure on CAR-Ts. I think when you talk to every single physician, I mean almost every single physician to a physician, they will say, CAR-T is curative intent. A TC is not. And so I always challenge physicians in the community with, if this was your loved one, what would you want? And to a person, they want them on a CAR-T. And the reason is because they recognize what the intent of the treatment is. And so really it goes into their mind of I have to think about the patients, will they have the right treatment team around them? Will they be able to be at the treatment center for that length of time? Will they be able to have the right support.

And so one of the big green shoots that recently happened for us was the reduction of REMS and the reduction of some of the patient burden in the label because as one physician told me, 4 weeks at a treatment center an academic center is like a sentence, versus 2 weeks is a vacation. Now I won't say who said that, and I won't determine whether that's true and either and maybe it depends on the academic center. But the bottom line is the point is 2 weeks is more rational for a patient and their caregiver to be away from family and other commitments to go receive a CAR-T. So I do think we expect some momentum coming from that decision. I also think the other dynamic is even if and when that momentum starts really building and you start seeing referrals increasing community physicians start seeing that they can get their patient back in 2 weeks, there will still be physicians and patients who want to stay physically treated in the community, which is why we have a huge push right now on bringing CAR-T to the community, literally infused in the community at a community center.

And we have 2 community centers today who deliver CAR-T in the community, that's Virginia Oncology and Tennessee Oncology, both successfully delivering CAR-T. As a matter of fact, Virginia Oncology treated over 90 patients. Dr. Simmons has been publishing on this, and he's successfully and safely delivered CAR-T. So I do think that's the other big green shoot is being able to bring CAR-T to the mega community centers so that CAR-T can be delivered closer to home.

Absolutely. And kind of perhaps zooming in even more near term to kind of delivering on some of this potential. We've seen Bristol perform pretty strongly over the last couple of quarters in the CAR-T space. Kind of -- is this down to kind of the manufacturing unlocks, the kind of out-of-spec kind of scenarios becoming more manageable. You've obviously had some new indications come in. We've had the REMS kind of, what are the most important factors that have enabled you to start competing in a way where if you contrast this with some of your other CAR-T competition that are going up directly up against Breyanzi, we're seeing slowdown there. And so what's different about what's supporting this particular performance for Bristol near term?

Yes. It's important to remind people kind of the journey Breyanzi has been on. So Breyanzi, when we initially launched, we were 3 years to market after the initial 2 CAR-Ts launched in the market. And we were constrained for our first 3 years. So that is not an ideal launch. But 3 months after being constrained and after working through a widening of our spec, it only took us 3 months to become the #1 CD19 CAR-T in the United States. We are now #1 in Germany, Japan and France. So it is that best-in-class profile that has really seen the surge. So when we talk about our current robust strong performance on Breyanzi, that's really the profile working very hard for us.

It's also the fact we have the broadest set of indications for B-cell malignancies. We expect also we have a PDUFA date this December for MCL. So it's that profile from efficacy, safety and manufacturing that has afforded us the opportunity. I think now, as I articulated, we do hope to see based on moving into the community and seeing some of that community growth. We also see much of Breyanzi's growth is in the outpatient. Again, back to a differentiation of Breyanzi. Breyanzi's safety profile allows people to move Breyanzi into the outpatient where those patients can be literally infused, sent home and monitored they're close to the center for a couple of weeks, and that is unique to its profile. And so what we are seeing now is most even academic centers are putting Breyanzi into the outpatient, which frees up capacity for them in their inpatient unit for CAR-Ts that they have to deliver in the inpatient.

And so for us, we think both profile and the REMS would afford us the opportunity to continue to grow. Now what I will say is CAR-Ts do have seasonality dynamics in the summer months. So we do anticipate seeing some seasonality, but we're really excited to see the second half grow for Breyanzi. Now as far as the REMS, everyone always asks me, how much do you think that class is going to grow. Honestly, it's interesting. Only 2 out of 10 patients today who are eligible for CAR-T are receiving CAR T. And so for -- and that should not be -- back to my point, if I were a patient and I think about being in the United States where health care and access to innovative care should be equal at minimum to France.

The question really is how do we get it to higher levels. And that's what we're working hard to do. But it will take time. Just the fact that the label updated, each center has their own SOPs. So each center will determine, am I going to implement this update immediately or take time. And we've done market research with all the major centers that deliver CAR-T today. And I think it's mixed. Some are immediately implementing the 2 weeks staying at the center and 2 weeks back into the community. Others are doing it patient dependent. So a high-risk patient versus some are doing it CAR-T specific. So they're picking certain CAR-Ts. They feel that they could administer outpatient. Of course, we're on the good end of that decision. And then some are still like doing a wait and see, like I want to wait and see. So I don't think that while the REMS is a green shoot, I don't think we're going to see this immediate pop for the CAR-T class. I think this will be something that takes time.

That slowly evolves. And kind of as you think about that eventual split of what might be achievable outpatient versus inpatient, what could the future look like in terms of how many patients are managed in a more outpatient way?

So I think it's really hard to put a number on it. I know everyone wants us to and I understand. But I think for us, it's very difficult to quantify that. I think what we -- how we think about it internally is make sure we're in the position to be able to supply in that place, and we feel very, very confident in that. And obviously, our goal is to make sure that the unlock for CAR-T happens for patients because to every patient I speak to that gets a CAR-T says the only thing I regret that was I didn't get it earlier that I went on to get other modalities where I was continually getting either infused or taking an oral and I had no idea I had an option like a CAR-T. And so for us, we will continue to work to get patients that ideal modality.

Absolutely. That makes a lot of sense. And maybe pivoting to kind of innovation, and I think there's quite a few fronts here. As we look at kind of your current later-stage pipeline, and you referenced a couple upfront, there is real innovation and kind of the targeting capability of the CAR-T, kind of you've got, your GPRC5D, you've got your dual kind of targeting options, which are kind of pushing the boundaries in terms of how we can apply CAR-T to some of these patients. There is also other innovations going on, the kind of idea of in vivo expansion, the idea of off-the-shelf CAR-T options, kind of as you think about long-term innovation in this space, what parameters are really important in innovation as you look at the portfolio that Bristol has or the portfolio that you would like Bristol to have over the long run?

I think it's a really, really great question. When we originally kind of got into the cell therapy business through the acquisition of Celgene, which acquired Juno and obviously, the partnership with Bluebird Bio. At that time, the world was an autologous world, but there was a further pitch growing on HD allos. And we took a very methodical approach of really understanding could an HD allo hit the efficacy bar that an auto CAR T could. And the first gen really struggled. And I think you guys have seen many of those companies kind of hit a certain state as a result of not hitting those kind of efficacy bars. But we have also recognized an autologous CAR-T will have a ceiling. And so if you believe in the power of cell therapy, then we need to be making and have been making investments to unpack off-the-shelf solutions as well as continuing to accelerate auto CAR-Ts because either in a world 10, 20 years from now where you might have coexisting auto versus HD allos versus in vivos or where a world where you start seeing some of these off-the-shelf take over auto CAR-T, you want to be in a position to be able to make multiple bets.

And so for us, we're excited that we are -- we've been patient, and we've waited until we have the right construct and tested that construct in multiple different ways. And we have our first HD allo that we are -- we've taken into clinic. We have our first visit for an HD allo. It's an HD allo for CD19 specifically designed for autoimmune we do think the highest proof of concept is in autoimmune. We say that because if you look at why the HD allo CAR-Ts have struggled in oncology, it is because they can't get that same level of persistence that's needed for the durable tails that you see and need in oncology. And that might not be needed in autoimmune because after all, what they're seeing to get this deep B-cell aplasia through the periphery and through the tissue, it does not necessarily need the persistence, it needs the depth. And so we feel pretty confident with our HD allo construct that it might actually be something that can achieve that.

So obviously, we'll prove that out in experiments and see if that scientifically works out. So we're quite excited to see that approach. But we've also been making investments in vivo. I think in vivo is an interesting platform. Obviously, it's much, much earlier and further out, but I think that is another great concept of can you potentially give a patient almost like a vaccine shot and provide them that same kind of CAR expression and so early data looks super intriguing and interesting. And so we've been watching that field quite closely.

Fantastic. And I think there's lots of kind of add-ons that you can think of in the in vivo space of how do we get that immune system response to be as robust as possible and as reactive as possible as well. Maybe zooming in on those kind of key pipeline opportunities. I think arlo-cel is kind of the nearest on the horizon and the one that people are spending a lot of time a lot of time on. Multiple myeloma is a pretty mature market when it comes to innovation, when it comes to the -- sorry, the cell therapy opportunities, but also when it comes to kind of the bispecifics, and you've got some players there being very dominant across different modalities.

How do you think about kind of your construct, why it's exciting and how you anticipate that entry in the market to look given the environment that you'll be entering?

Yes. So when you look at the multiple myeloma market, you still see a market where we haven't yet found a cure where we still have patients that are progressing. And now we have a market where we have patients that are quad, class exposed and really have nowhere to go. And so when we think about the role of GPRC5D, we see a growing marketplace of opportunity because more and more patients as BCMA TCs and CAR-Ts move up into earlier lines, you're having more of those patients that are quad exposed and needing a place to transition to after.

And so what we're excited about arlo-cel it gives you optionality. And we talk to a lot of physicians. And initially, when we saw our data, we were really excited about its efficacy. I think what the 2 big ahas for the field were, one was it actually -- the efficacy looks great in BCMA naive as well as BCMA exposed. So that was very intriguing for physicians. So they were pushing us to look at BCMA naive. And then the second was really a safety profile. I think a lot of people understood that 5D was a relevant target in multi myeloma. But the challenge was ongoing pressure on that target really has very high unwanted tox profile.

And so from our standpoint, based on what they've seen with the TC that was in the market. And so when they were able to see putting pressure on that antigen one time actually gives you the efficacy benefit, but without as much many of the liabilities of the on-target off-tumor toxicity. So from that standpoint, we really are excited about arlo-cel. So as you know, we have 2 registrational studies ongoing right now. The first one, obviously, that we expect for data for next year is our relapsed/refractory multiple myeloma for that quad-exposed population. So we're super excited about that based on what we saw in our Phase I. So we hope to see that data play out in our pivotal. And then, of course, we've also begun our earlier QUINTESSENTIAL-2 trial that, that actually is in the second line to fourth-line patient population. So we're quite excited about the promise of that asset and what it can bring in the marketplace.

And it certainly sounds because you're going after a different target, your kind of flexibility around sequencing is much more likely to kind of give you potential for utilization in a number of different places for a number of different patients. Is that how you taking the opportunity...

100% how we think about it. The one thing you can talk about multiple myeloma, there's lots of assets, but there's lots of strategies. In other words, it's very heterogeneous, not only in the patients, but also in how physicians treat. And I think having assets that give you utility across multiple different approaches is very flexible for physicians and flexible for patients. So I think that's what GPRC5D offers.

Absolutely. I think the more we see that physicians have tools at their disposal, the more art kind of that comes into the way that they deploy their science. As we look at kind of that pivotal readout in 2026, kind of what should we be expecting to see? Kind of how should we be thinking about that particular readout? And also, we're seeing a lot of changes in the FDA, HHS, et cetera. And I know that this is a line that all the companies are having to navigate and walk.

Can you just talk about any interactions that you're having with kind of the bureaucracy and with the policy side of the equation? As to whether this will look different or similar to what we've seen be applied to cell therapy in the past.

Yes. So far, the FDA has not -- we've had no experiences that would make us feel as though that either advice they have been giving us on an ongoing basis has changed. And one of the greatest signals I've said to people that they have to remember, the label updates with the REMS, which started with Peter Marks, then handed over to Nicole Vern, but also brought over the loan by Bernad Prasad. So I honestly have not -- we have not seen any changes in the FDA's temperament.

Obviously, there's been reasons that people have concerns and questions, et cetera. But when it comes to GPRC5D, this is an asset, the primary endpoints are not tied to MRD. I think that's everybody's question mark. This endpoint is not tied to that. And so we do expect no issues from that standpoint. And we hope that we can replicate what we saw in Phase I, which was a very promising efficacy and safety profile. So that's what we hope to bring to the market.

Fantastic. Fantastic. I think we'll be looking at that one very, very closely. The other thing that I wanted to ask is you're now looking at the dual targeting, is the next kind of cab off the rank as we think about after arlo-cel. What do you hope to achieve there, particularly in the context of the sequencing conversation we just had and kind of the use of BCMA kind of targeting agents across the board in multiple myeloma. How do you think about kind of this opportunity. And we've also seen kind of bispecifics kind of on the mAb side of the equation, cause different types of outcomes or different types of tox for patients as well as we look at kind of more dual targeting in the cell therapy space. Is there anything we need to watch out for there?

I think what people have to remember, there's still an enormously high unmet need in this newly diagnosed multiple myeloma patient population. As we think about the dual CAR, we are looking to try to bring an asset with curative intent up into that newly diagnosed patient population where the unmet need is still really high. There is still a lot of physicians who say in their mind, while some of the CAR-Ts have proven to show really great efficacy, they come with some liabilities and concerns and those liabilities make them wonder, should I be exposing a patient into an earlier line like a newly diagnosed patient or should I be waiting because of the risk-benefit equation. So what our hope is here is that we can balance both great efficacy and deep durable responses along with a safety profile that would allow it to address that still remaining high unmet medical need in newly diagnosed multiple myeloma.

So we are obviously excited about this asset. We are moving forward at a very high pace in our dose-finding trial. And we're looking forward to hopefully being able to release data on that and really hopefully see what kind of asset we have. The reason we're excited about it as well is 2 things. One, if you remember, and it was an ASCO/ARGO, which seems like an eternity, when you started seeing bispecifics hitting 5D as well as, you were seeing tremendous efficacy. But what you were seeing was a lot of safety liabilities, which I think is what you're alluding to. And we do believe back to what we've seen with GPRC5D, when you put pressure on targets on time and especially excuse me, I should say, in a bispecific designed CAR, you are also getting the nature of avidity. So you're not only putting pressure once, you're getting avidity, which we do believe will buy down some of the side effect liabilities.

Now obviously, data will have to prove that out. That's why we're doing the scientific experiment. But we do have a lot of enthusiasm for what this can bring. And I can tell you for the physicians who are involved in this trial, there's a lot of excitement building for this approach.

Fantastic. And I did see that you had the Iber data that came out this morning, also in the multiple myeloma space. We won't dive into that deeply here, but it seems like kind of Bristol is going to be in that position to be able to play across kind of a number of different assets as well, which is obviously valuable.

Super important for multiple myeloma leadership as a company.

Absolutely. I did want to make sure that we've had a good chance to spend some time on immunology. And this is because as I think about CAR-T, and I think the way that you set this up as well, this is the next frontier as we think about kind of where this innovation and technology can be deployed. Maybe just starting at the highest level, a very simple question. What kind of patients are potentially relevant for CAR-T when we think about immunology. Is it the sickest of the sick that have been kind of experiencing kind of very refractory kind of autoimmune diseases? Or is there a path to this being a broader patient population?

So right now, obviously, our trials are designed for kind of that refractory severe population. I think there's 2 things to remember. One, that's naturally where we should start, obviously, to kind of understand the risk benefit of the modality in this patient population. But what I have to always remind people, including internally, that hematology, when you compare the population that CAR-T is in today there versus the severe refractory population in autoimmune, you're talking anywhere between 3 to 5x the patient population size. And the reason for autoimmune disorders are much bigger populations than what we see in hematology.

So already, you see a very sizable marketplace. But what we've also been seeing based on the data that's been already out there in the marketplace, including our own in auto-CAR-Ts, a lot of physicians are saying, well, listen, a lot of the severity has been organ involvement and organ damage. Some of it's not reversible, and this is why people have seen some of this proteinuria that exists in SLE, for example. And the reason for that is you can't reverse organ damage. And so there's a lot of physicians who are pushing us to try to move these things into more of these mild to moderate patient severity.

Obviously, that will determine based on when these profiles completely read out because, of course, you want to be able to say, can you replicate what you did in kind of the early work in your later work? And if that does happen and you start seeing a risk-benefit profile be such, of course, you're going to see both patients and physicians want to move these into earlier lines or in this case, into patients without as much severity or organ involvement.

Fantastic. And just kind of understanding that scale of even the refractory patients is quite impactful when we think about the long-term opportunity, as you said.

And I can't help but go back for a second for the patients because I think about some of our patients that we've already treated with our CD19 CAR-T that we've published on or at AACR. I mean, these are patients in their 30s. I mean we -- these diseases are robbing them of their life. And so to think about what a CAR-T has now provided these patients who are now treatment-free and disease-free. I mean these were patients that were told about their diagnosis and they were told that they were going to be put on immune modulators through the rest of their life, some of them with such high doses of steroids that they would not be able to rear children and to be able to think that they could potentially get a CAR-T and have one of these responses and have a new lease on life. And so for us, the excitement is really palpable and what's potentially here for patients.

Absolutely. Absolutely. And I think kind of this investment in the CAR-T space and immunology has been part of a perhaps broader rethink of Bristol around immunology kind of we saw your spin-off more recently. And I think you spoke in that announcement in terms of really focusing on assets that have the potential to reset the immune system and promote tissue repair and that ability to invest in areas where Bristol is kind of best positioned to lead. As you think about kind of this similar to how we just mentioned on the multiple myeloma space, kind of multiple assets there that sit around the CAR-T space. Do you think about the ideal portfolio in the immunology space, kind of what role does CAR-T have in that strategy?

So when it comes to the immune reset, I think it's really the cornerstone, right? Because the efficacy bar has been established by auto CAR-Ts. So what everyone is now doing, including ourselves with the -- moving our HD allos CD19 into the clinic is trying to determine, can you reach that same efficacy bar with a more off-the-shelf solution so you can bring it into the community rheumatologists offices. And so when we think about kind of where CAR-T sits, we think it has set the bar. And the question is, can we replicate that with other shots on goal, and that's what we're continuing to explore as a company.

That's super exciting. And maybe just diving into the CD19 NEX-T. Tell me about that asset and why this asset feels like the right one for you to really pursue at this point in time with what we know about CAR-T in the immunology space.

The first thing that people need to know about our CD19 NEX-T is Breyanzi's construct that we put on to a shorter manufacturing process onto a single train. And so we have years and years of understanding translationally clinically in manufacturing from Breyanzi that has fueled our excitement on what this construct can bring from an efficacy and safety standpoint.

So that understanding builds really great excitement. And then, of course, we've now seen this product perform in multiple different disease areas from SLE to MS to scleroderma and myositis, et cetera. And we're really excited about what it's performing and what we hoped it would do as far as getting deep B-cell aplasia, both in periphery and the tissue and making sure that we truly induce this immune reset. And what we're seeing is these patients indeed are coming off their immune modulators and are disease-free. So this for us is why we're really excited about this asset and its potential. It's why we also were really aggressive in our CDP, our clinical development plan. We have Breakthrough 1, Breakthrough 2 as well as our breakthrough SLE, all kind of in parallel.

Typically, in autoimmune, you kind of test an asset in a disease, you wait to see what it does and then you kind of move into other diseases. And we have been so bold based on what we saw early that we wanted to go out into these basket trial designs to go after multiple populations at one time to be able to accelerate kind of our position across multiple indications, I should say.

Absolutely. And I think kind of this there's so many pressures on pharma companies and on kind of pharma innovation that it's becoming more and more important to take on risks like that because you've got competition coming or because you've got kind of -- maybe not in the CAR-T space in the same way, but you've got kind of the Inflation Reduction Act kind of kicking off your time. You've got kind of the need to run those parallel trials in a way that perhaps in the past would have been sequential. And so balancing that risk reward becomes really complex and really important.

As we think about this innovation, kind of we've talked a bit about the science on the immunology side and why this is exciting. We began this conversation though with kind of why has this been hard for us to achieve real impact on a broad basis in heme. As we look forward in the immunology space, what needs to happen? And what are you doing today? And what do you anticipate doing over the next 3 to 5 years as you're advancing this asset in the clinic to make sure that kind of your rheumatologists, your other kind of immune doctors, inflammation and immune doctors around the world are in a position to deploy these products for the right patients at the right time.

Yes. We asked this very question when we decided to put this asset in the clinic was what would have to be true for this to be a meaningful market. And it's why right upon putting into clinic, we developed something called the Action Network. And it is a body of physicians who are advising us at the top rheumatologists along with hematologists and neurologists, informing not just how to clinically unpack a CD19 CAR-T, but also how do we actually create an ecosystem that allows for rheumatologists and hematologists to work more in partnership to both identify who's eligible for these CAR-Ts, but to ensure that these patients get access to CAR-T because we recognize if it was a struggle in lymphoma for only 2 in 10, it will be a bigger challenge in rheumatology. And so we have started the work now, not upon approvals to create an ecosystem that allows for CAR-T to be more broadly used.

Fantastic. And can you contrast for me kind of the U.S. versus the ex U.S. space here because I think health care systems look really different around the world. The treatment of physicians often look different. Even the kind of degree of innovation that's made it from the U.S. to the ex U.S., particularly in the immunology space can be quite drastically different. And so how do you see this becoming either a global product or more of a U.S. kind of opportunity in the first years?

We are certainly designing this to be a global product. And my first measuring stick on whether or not there is global interest is how well the trial is recruiting. And I can tell you globally, the trial is recruiting really well. And so there is a high desire in markets to be able to bring this type of innovation to patients. And so for us, that's why we are working not just in the United States to create this ecosystem. Many of the people on our action network are not just United States-based, but they're also European-based, et cetera.

So we are looking to try to help support an ecosystem more broadly. But the dynamics you're talking about are real. There are some markets where those dynamics are harder where the receptivity to innovation and the price of innovation is not there. And obviously, that makes it a bit more challenging. But certainly, I think when it comes to the desire to deliver that kind of innovation to patients, that is very -- that exists in every country we've been bringing CAR-T into.

Absolutely. And so maybe in our last kind of few minutes, I would love to just get your thoughts on if you're sitting here in this role in kind of 5, 10 years in the future, what does cell therapy look like at Bristol by then? And kind of what will you feel kind of needs to be true for Bristol to have said that we've succeeded in delivering against the opportunities in the cell therapy space?

No, it's a great question. It's when we have our vision statement around unlocking the full potential of CAR-T is grounded in us delivering this transformational modality to over 100,000 patients. And I do know that when we first made that ambition 4 years ago, it didn't feel fully plausible, but you wanted to have people starting rallying behind something that seemed maybe a bit impossible, but to then see them along the way, making it possible. And we're getting there through strides of innovative science that's moving into other disease areas. We're getting there through moving to automation for our autologous, and we're going to get there also by moving to off-the-shelf designs and solutions.

So for us, success looks like that not only do we achieve the 100,000 patients that we see patients in diseases where functional cure wasn't possible at is possible. And that to us will be something that I hope in 5 years, I can sit in front of you at this panel and say that we've done.

That is fantastic. And my final question because I think this is always a fun one is -- what are the questions that you get that you think kind of you want to clarify? Like is there something where you say people really misunderstand this thing about kind of cell therapy and about our opportunity going forward?

I do think it starts with when people kind of say why CAR-T. And then I remind them to put them in the shoes of a patient and say to themselves, would you like door #1 is 1 and 2 chance, and this is -- I'm talking about diffuse large B-cell lymphoma, but diffuse large B-cell lymphoma, you're progressing off R-CHOP within 12 months. Do you want door #1, which is a onetime infusion that you have a 1 in 2 chance for a cure? Or do you want door #2, where I'm not going to give curative intent, but I'm going to be able to treat you and you might have a long PFS, but you're going to be coming in for ongoing doses, et cetera.

I mean I just don't know a person in the planet who chooses door #2. And so for me, it's that constant reminder of why door #1. It comes with additional complexities and other considerations. But for me, that's what we should be good about in the health care system is how do you remove those complexities so that more patients can choose who are #1.

That's fantastic. And one thing that you said earlier on that I do want to finish on, you spoke about the fact that kind of a 2-week vacation is very, very different.

That was the physician who said that.

To the longer-term version. I have just spent 5 weeks living out of a suitcase. And I can tell you 2 weeks living out of a suitcase is so much nicer than 5 weeks to be honest. I do resonate with that perspective. But thank you so much for time and all.

Thank you, Courtney.

This has been wonderful. I feel like we've managed to dive into a whole lot of detail around kind of where Bristol is going in the future and kind of what unlocks are required in the cell therapy space. And we're really excited to see this innovation come to patients and have real impact. So thank you so much.

Perfect. Thank you so much, Courtney. Appreciate it.