Bristol-Myers Squibb Co at Guggenheim Global Healthcare Conference Transcript

The following is excerpted from the question-and-answer section of the transcript.

Question: Seamus Fernandez - Guggenheim Partners - Analyst : So maybe, Samit, just to start big picture rather than diving right into some competitive data. Let's start with six months ago, we saw Bristol stock at $40 a share, sentiment uniquely cautious. And while the threat of generics is unchanged, shares are now trading at $55. From your position in R&D, obviously, what's changed? Samit Hirawat - Bristol-Myers Squibb Co - Executive Vice President, Chief Medical Officer, Global Drug Development, Member of the Leadership Team I think those shares might be a little bit different right now.

Question: Seamus Fernandez - Guggenheim Partners - Analyst : Great. And Robert, maybe you can just chime in on the sort of the focusing of the portfolio and working with Samit to really kind of streamline the portfolio.

Question: Seamus Fernandez - Guggenheim Partners - Analyst : Great. And there's I guess, risk profile in drug development and kind of the consideration of competitive assets. We just got competitive data this morning. What -- in terms of your sort of team development approach drew you to COBENFY and what sort of maintains and sustains your excitement for that program and that product as we enter the sort of full launch in 2025 and advancing from there.

Question: Seamus Fernandez - Guggenheim Partners - Analyst : Right. And when we just sort of think about the big opportunities incremental to schizophrenia, obviously, the things that come to mind are always bipolar depression sort of first and foremost as a major driver of commercial uptake and commercial opportunity. But Alzheimer's agitation is also seeing a resurgence. Maybe talk a little bit about the profile that you think COBENFY offers in Alzheimer's agitation in particular? And then what's the hope for this mechanism in bipolar depression potentially? (multiple speakers) Samit Hirawat - Bristol-Myers Squibb Co - Executive Vice President, Chief Medical Officer, Global Drug Development, Member of the Leadership Team It's Bipolar Mania -- . Because -- .

Question: Seamus Fernandez - Guggenheim Partners - Analyst : Okay. And then for one of the critiques of COBENFY has been, one, tolerability is sort of one critique. But maybe the bigger one that some physicians we've talked to have sort of critiqued as the twice-daily profile and the challenge of treating a schizophrenia patient with a twice-a-day drug. How challenging is that in your view? And then separately, what are you doing to basically potentially bring a once daily or perhaps even a long-acting? Samit Hirawat - Bristol-Myers Squibb Co - Executive Vice President, Chief Medical Officer, Global Drug Development, Member of the Leadership Team Yes. So the intent is not to convert it to once daily because of the metabolic profile of the drug, we certainly do believe that the -- first of all, getting the ratios right was very important, and Karuna did a wonderful job. In defining the ratio of xanomeline to trospium 5:1. In the first studies of schizophrenia and then did the study in healthy elderly volunteers to look at what would be required for AD psychosis and there, the ratio is 10:1. And so that has been taken forward as a 3 times a day dosing because of the metabolism that occurs. But remember, patients with schizophrenia. They are -- how many drugs they are already on. On an average, there are five to seven drugs they're already on. So adding another one that has a side effect profile that is very different than what they are taking today, the atypicals. And that certainly bodes well as well as seen differently from physicians and patient perspective. So as the beginning, we are starting with a monotherapy for COBENF. But the adjective schizophrenia trial is ongoing, which adds COBENFY on top of the background therapies. So what we've not heard, and certainly, had the data read out differently for Emraclidine, this would have been a continuous dialogue [QDID, QDBID]. But right now, I think BID is what we have. And we have not heard anything major in terms of BID is going to be a detriment to prescribing it, et cetera. And the easy way to think about it, take it as soon as you wake up and take it as you're going to sleep. So BID fits from that paradigm perspective, and that's the way physicians also think about it. Patients will be thinking about it. We have not heard anything wrong, anything untoward from that perspective. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies.

Question: Seamus Fernandez - Guggenheim Partners - Analyst : Great. Robert, you mentioned Milvexian. We got some updates on the third quarter results conference call. Maybe you could just walk us through some of those updates, but also a little bit of the battle that you've actually had to fight in the wake of another competitive failure. I mean I would also argue like thankfully, this other -- maybe the trial hadn't failed of your own Phase 3 clinical program. As it relates to COBENFY. But the Asundexian situation from buyer really put -- was a headwind for the Milvexian program. Maybe tell us how you feel about it today.

Question: Seamus Fernandez - Guggenheim Partners - Analyst : And your confidence and conviction that the result is just like clearly is not an asundexian result seems extremely high at this point. Can you just remind us why it's so high? Samit Hirawat - Bristol-Myers Squibb Co - Executive Vice President, Chief Medical Officer, Global Drug Development, Member of the Leadership Team So what we saw in our clinical trials, as Robert pointed out, we did see a dose dependent an increase in efficacy without a dose-dependent increase in safety or bleeds. Second, the preclinical experiments and now, of course, we've seen the clinical experiment as well, asundexian had 3 times the event rates for strokes and thrombosis as opposed to Apixaban within the same study. Apixaban actually overperformed compared to what the assumptions are. If you recall our assumption in our clinical trial at the end of the study would be 1.33 events per 100 patient years. Apixaban was 1.03, asundexian was 2.33, I think. And so when we look at our trial, our event rate, blended event rate overall in a blinded fashion is running much lower. So as we go forward, picking the right dose without added safety issues because the DMC continues to look at the data, gives us confidence that we are in the right direction. And they said they didn't say no to us increasing the sample size as well. So I think overall, we feel good where we are. But of course, when the Phase 3 reads out, then only we'll know what ultimately transpires.

Question: Seamus Fernandez - Guggenheim Partners - Analyst : Great. Maybe we'll shift gears a little bit. We have some data earlier data coming up very soon, maybe even in the middle of this week. At ACR, can you maybe just help us understand the profile and the opportunity that you see for CAR T therapy in immunology, in particular.

Question: Seamus Fernandez - Guggenheim Partners - Analyst : It seems pretty high impact would be an ability to just sort of sustainably reduce or even eliminate prednisone, oral prednisone, things like that.

Question: Seamus Fernandez - Guggenheim Partners - Analyst : Great. In terms of sort of other assets, there's a lot going on at Bristol. Maybe we can sort of take a quick step back and go through -- Samit, I went through this earlier, so we can go through -- the family tree of assets that are coming. But if you wouldn't mind, maybe walk us through the assets that are most important, and then it'll will give us an opportunity to walk through LPA1. Samit Hirawat - Bristol-Myers Squibb Co - Executive Vice President, Chief Medical Officer, Global Drug Development, Member of the Leadership Team Yes, absolutely. So maybe I'll change my family tree a little bit because the big brother I said was milvexian, but today morning, I think it's Milvexian is now Twin Brothers with COBENFY, which is already there. And both of them are going to be very critical. And I think the way to think about it is for COBENFY, there is pretty much a readout for an indication every year until the end of the decade. So next year, we're looking at ARISE. The year after that would be ADAPT. The year after that could be agitation. The year after that could be bipolar, the year after that could be cognition, the year after that autism. And of course, in between whatever else might come because even in AD psychosis, there are two indications. There is the acute and then there's a relapse prevention, for example. Both studies are ongoing right now. If you think about Milvexian, we've talked about in '26, two studies read out, '27, third study reads out. This year itself for (inaudible), you have the readout of psoriatic arthritis, 2 studies before the end of the year. And then in '26 will be SLE and '27 will be Sj÷gren's. If you think about Camzyos, next year, first half, non-obstructive hypertrophic cardiomyopathy. And then we have Reblozyl reading out next year for myelofibrosis, the independent study, and then there will be a lot of the Phase 1 data that comes out. '26 is a big year. '26, we'll have the radioligand therapy first Phase 3 study that should read out. GPRC5D, multiple myeloma study should read out. Iberdomide, one study should read out. Mezigdomide, at least one of the studies should read out for multiple myeloma. SLE, I've already talked about, what else am I missing out? (inaudible). (inaudible) is late though. [Vketamide] would be late because that's first-line diffuse large B-cell lymphoma. And then once we start the other studies, then it will add on. So early pipeline will start a lot of studies next year as REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies.

Question: Seamus Fernandez - Guggenheim Partners - Analyst : Maybe an unfair question. -- Samit Hirawat - Bristol-Myers Squibb Co - Executive Vice President, Chief Medical Officer, Global Drug Development, Member of the Leadership Team And by the way, CD19 CAR-T for SLE. (multiple speakers)

Question: Seamus Fernandez - Guggenheim Partners - Analyst : So let's maybe move back to immunology. There were some programs that you didn't mention in immunology that I think are worth talking about. You have a positive cendakimab result. It was just presented at a recent meeting in [EoE]. Maybe just give us your thoughts on that program. And REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies.

Question: Seamus Fernandez - Guggenheim Partners - Analyst : It's an unfair question because we're not talking about commercial, but the clinical commercial. Samit Hirawat - Bristol-Myers Squibb Co - Executive Vice President, Chief Medical Officer, Global Drug Development, Member of the Leadership Team No, I think the way to think about it, we presented the data, as you said, the trial did meet its endpoint. And we now -- the discussions that we are having is putting in the context of what is the incumbent right there. And it's a very strong incumbent that's out there. So we'll have to put all of that in that framework as we think about conversations on regulatory path and moving forward. I don't have an answer for you as to what the time lines are and how it looks. But those are the discussions that we truly have to have on the table. And that's why we have to keep in mind the commercial opportunity, what it truly is and then make the decisions on the time lines and what the next steps would be.

Question: Seamus Fernandez - Guggenheim Partners - Analyst : Multiple Myeloma, the level of expertise there is obvious, unquestionable. The dynamics in the market in Multiple Myeloma, I think are interesting. But when you look at the pipeline, Robert was talking about segmentation. How important is segmentation going forward in Multiple Myeloma and how is Bristol approaching it? Samit Hirawat - Bristol-Myers Squibb Co - Executive Vice President, Chief Medical Officer, Global Drug Development, Member of the Leadership Team Yes. I think it's a natural segmentation because of the modalities and because of the need. As things start to become used earlier and earlier, unfortunately, because the disease is not being cured, you're accumulating the prevalence population as you go later and later. So as we think about, we just saw the data of CD38 getting into a newly diagnosed patient population. So what happens as we look to the future as cell therapies like [BCMA] or CAR T or move earlier, what happens after that, as T-cell engagers move earlier what happens after that. And I think we're only talking about biologics right now, but small molecules will have their own space. because combinations are just easier with the small molecules, hard to combine CAR T with something, hard to combine T cell engages for their profile with something right now. So we'll have to continue to find what is the best way to continue to provide combination therapies for better outcomes from an efficacy and tolerability for these patients. And that's why we've taken a multi-modality approach to it. First, we have this small molecules. We were developing a bispecific or rather the -- yes, the T-cell engager aloptimab, which we took away because we were not going to be first. In fact, we were going to be fourth or fifth. So we took that away. But we have the broadest cell therapy approach to it. So [Beckman] was the first one. GPRC5D is the second one. And the third one is a dual card, which is the BCMA and GPRC5D on the same car. So that's the third one. We hope that GPRC5D applicability, pre and post BCMA is BCMA to be equally important. But if you can then further improve on that, maintaining the safety profile with a dual car, taking BCMA and GPSC5D, that would -- that can be a game changer if the safety profile is tolerable because you know both nodes are important. You know we've seen the data when the two T cell engagers were combined, the response rate was like 97% or 96%. But the problem was the safety profile. So if you can get the same outcome with a better safety profile, that could be a real game changer in this patient population. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies.

Question: Seamus Fernandez - Guggenheim Partners - Analyst : Right. And coming up, we've got ASH. It's right around the corner, it feels like, but it will still probably feel like it's decades away. -- Can you maybe just walk us through what's coming at ASH. Are you excited about anything that could be presented there? Samit Hirawat - Bristol-Myers Squibb Co - Executive Vice President, Chief Medical Officer, Global Drug Development, Member of the Leadership Team With the portfolio that we have in hematology, we have to be excited, right? There's so much happening. And there will actually be an encore, by the way, although it's not a rheumatology meeting, but there will be more data presented for the cell therapy CD19 in autoimmunity at ASH. But beyond that, I would say watch out for gold caramide data, further updates on the large B-cell lymphoma as well as I think follicular lymphoma is there as well. If you think about Mezigdomide, more data being presented over there, especially novel combinations. As we think about the Mezigdomide cell therapy, cell therapy data should be the additional cell therapy data, including GPRC5D updated data that will be presented over there. What am I missing?

Question: Seamus Fernandez - Guggenheim Partners - Analyst : Okay. Great. Maybe go to some other assets, HFpEF, the EMBARK study, you mentioned the opportunity there. And I guess, with the second-gen 224 asset. Can you just talk a little bit about what sort of separates the two? What you think is going to really differentiates 224 from CAMZYOS?

Question: Seamus Fernandez - Guggenheim Partners - Analyst : Great. This is sort of like a random walk down Wall Street conversation on the very robust portfolio of choices that we have to go to. But LPA1, we haven't talked about yet. Let's kind of go through the opportunity in IPF and PPF. As well as, again, what differentiates your LPA1 program from some others that have been challenged separately?

Question: Seamus Fernandez - Guggenheim Partners - Analyst : Great. So I think we only have two-minutes left, slightly wrong up there. But -- maybe just we -- I think we went through a little bit of the family and the grandchildren as well. But if you were to just sort of say, okay, these are data sets that I'm particularly excited to see in the next 12 to 18 months in the sort of Phase 2 plus time frame. What are you most focused on? Samit Hirawat - Bristol-Myers Squibb Co - Executive Vice President, Chief Medical Officer, Global Drug Development, Member of the Leadership Team So I mentioned a lot of them in terms of the Phase 3's. So all of those are going to be important from a company perspective and our own drug development progress and research perspective. Beyond that, so beyond the general ones that I've already spoken about at Milvexian, GPRC5D, COBENFY and SLE. So all life cycle management in the Phase 3 program. The ones to watch out also are going to be the anti-TAL molecule. It's in randomized Phase 2 study right now. That is '26 and '27 time frame and it's because it's a long follow-up that you need for these patients. So that's going to be important. Another drug that we are taking into Phase 2 is [fine MAGLipase] inhibitor. Again, dual inhibitor, very there are lots of others who are doing it as singular inhibitors. The dual inhibition approach that we are taking in Alzheimer's disease is going to be important. So watch out for that again, '26, '27 time frame. Some of the early data that is going to be emerging in next year and the year after would be the [radiolagon] therapy in breast cancer and small cell lung cancer, that's going to be important. As well as, I think 2026 will be [GPC3 perocelucarcinoma for radioligntherapy] that's going to be important. I think from cell therapy, next year, watch out for data for not only continuous emergence of SLE, but as we think about data from the sclerosis or scleroderma perspective, myositis perspective and then hopefully, MS as well that will come out. So I think these are ones that we don't normally get to talk about. And one molecule that I know Robert and I are both passioned about CCR8 in oncology, looking at certainly impact on Treg and then combination thereof with PD-1 inhibitors and immuno-oncology agents. So those are all going to be very critical. And I know today, thankfully, we didn't talk about OPDUALAG because I get 15 questions every time. But OPDUALAG is another one which is going to be important, and you'll continue to see emergence of that data. I think next year, we'll be able to talk about the overall survival data from the randomized Phase 2 study that we conducted. So that data will read out next year as well. So that will then hopefully give you a little bit more confidence as to why we plan the study, the way we planned it and execute on the Phase 3. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies.

Question: Seamus Fernandez - Guggenheim Partners - Analyst : And I'll apologize to all the people who are looking for a laundry list of BD development targets from Bristol-Myers Squibb. I didn't even get to that question because there's plenty going on. So thank you so much for joining us. Really thrilled to have both of you here with us today. Samit and Robert, thanks for taking the time. DISCLAIMER Refinitiv reserves the right to make changes to documents, content, or other information on this web site without obligation to notify any person of such changes. In the conference calls upon which Event Transcripts are based, companies may make projections or other forward-looking statements regarding a variety of items. Such forward-looking statements are based upon current expectations and involve risks and uncertainties. Actual results may differ materially from those stated in any forward-looking statement based on a number of important factors and risks, which are more specifically identified in the companies' most recent SEC filings. Although the companies may indicate and believe that the assumptions underlying the forward-looking statements are reasonable, any of the assumptions could prove inaccurate or incorrect and, therefore, there can be no assurance that the results contemplated in the forward-looking statements will be realized. THE INFORMATION CONTAINED IN EVENT TRANSCRIPTS IS A TEXTUAL REPRESENTATION OF THE APPLICABLE COMPANY'S CONFERENCE CALL AND WHILE EFFORTS ARE MADE TO PROVIDE AN ACCURATE TRANSCRIPTION, THERE MAY BE MATERIAL ERRORS, OMISSIONS, OR INACCURACIES IN THE REPORTING OF THE SUBSTANCE OF THE CONFERENCE CALLS. IN NO WAY DOES REFINITIV OR THE APPLICABLE COMPANY ASSUME ANY RESPONSIBILITY FOR ANY INVESTMENT OR OTHER DECISIONS MADE BASED UPON THE INFORMATION PROVIDED ON THIS WEB SITE OR IN ANY EVENT TRANSCRIPT. USERS ARE ADVISED TO REVIEW THE APPLICABLE COMPANY'S CONFERENCE CALL ITSELF AND THE APPLICABLE COMPANY'S SEC FILINGS BEFORE MAKING ANY INVESTMENT OR OTHER DECISIONS. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies.