Bristol-Myers Squibb Company (BMY) Earnings Call Transcript & Summary

Great. So good morning, everybody. Thank you for joining us for our next session here at the Leerink Global Healthcare Conference. It's very much my pleasure to welcome Roland Chen, who's Head of Development for immunology, cardiology and neuro at Bristol-Myers Squibb, and thanks very much for making the trip to Miami and being with us here today. I thought it would be great for you to just touch on your background briefly, so people get to have a little bit better sense for your experience and how you spend your time at Bristol and then we'll go from there.

Thanks, Dave. It's really great to be here. So just by way of introduction, I've been at Bristol for about 25 years now. Most of it has been in the development area, but also time spent in our safety organization as well as in outcomes research. It's a very exciting time here at BMS. And currently, I had immunology, cardiovascular and neuroscience development. And really, Dave, that's where I allocate most of my time and going ahead.

Excellent. Excellent. Great.

So with respect to the Phase III trials that you're most excited about and before you go into the specific therapeutic categories, could you talk about the big cards that are turning over, over the next couple of years?

Yes. Thanks, Dave. It's a really exciting time here at BMS for us. We have an extremely rich and innovative pipeline of assets with a number of key pivotal late-stage readouts coming over the next 2 years across the therapeutic areas. Mean just to touch on a few highlights in cardiovascular, we're looking forward to the readout of our ODYSSEY study. And the second quarter of this year of Camzyos in patients with a non-obstructive form of HCM. As you know, Camzyos is our first-in-class approved treatment for patients with symptomatic obstructive HCM. This is in the non-obstructive form an area where there is a high degree of unmet need without good treatments. And so we're excited about that. Staying with cardiovascular, we're looking forward to readouts in 2026 for milvexian in ACS and SSP. Milvexian being our novel oral Factor XIa inhibitor that we think has the potential to offer efficacy on a par with Eliquis, but with an improved bleeding profile, and we're looking forward to readouts there, followed by a readout in 2027 from our Librexia AF study. This is a head-to-head study against Eliquis. And we're very excited about this opportunity to be potentially the only indicated oral Factor XIa inhibitor for patients with AF. I think moving to neuroscience, we're very excited about the near-term readout for Cobenfy in the ARISE study in Phase III and patients in an adjunctive schizophrenia. This is an area, again, where there's a high degree of unmet need, and we're looking forward to Cobenfy's readout here. I think it's exciting, particularly, Dave, because Cobenfy has an M1, M4 novel dual agonist really represents the first novel mechanism for patients in schizophrenia in decades. And this is going to be followed by data later on in this year from the ADEPT-2 study. Really exciting to see what Cobenfy potential is in Alzheimer's disease psychosis, an area where there's no approved therapies. And that will be followed by data readouts in '26 from ADEPT-1 and ADEPT-4. And then finally, in the immunology space, we're highly excited about at [ Milperon ], our novel first-in-class LPA1 antagonist. We are looking forward to data in '26 in patients who have idiopathic pulmonary fibrosis followed by data in progressive pulmonary fibrosis. Again, an area where there's really not great treatments in an area where there's high unmet need. And then with SOTYKTU readouts in 2026. Two studies in SLE followed by a readout in '27 with Sjogren's syndrome. It's a really exciting time. These are just studies in the areas of immunology, cardiovascular and neuroscience. There are others that will be reading out in areas that I'm not responsible for. So really an exciting time for Bristol.

Excellent. That's great. So maybe before I go into some of the more specific questions on individual drugs. I did want to ask a high-level question. So clearly, and you're not in charge of commercial, but clearly, the plan was for SOTYKTU to be an extraordinary success with exceptional head-to-head data versus Otezla yielding dramatic uptake and market share shift away from Otezla 2 SOTYKTU but that hasn't happened. So I don't know, how does that inform your development thinking, right? I'm not trying to suggest that running head-to-head trials that succeed won't pay off. But just how does that inform your thinking in R&D as you work with your commercial colleagues on development Phase III projects.

Yes. Thanks for the question, Dave. As we've stated, dermatology is an extremely competitive area. It's highly managed with payers. There's a lot of therapies that are available. And so when we step back, and we think about how we are and we will continue to develop, our focus is really on developing assets that we think can meet our high bar for success, one, and then also in areas where we think we have an advantage, where we have the ability to develop in meaningful ways and where we have a competitive advantage. So I'll give you some examples. I think if you go back even with cendakimab, cendakimab in Phase II showed positive findings in atopic dermatitis but that didn't really meet the bar that I just laid out, those 2 criteria. And even when you think about Phase III data in eosinophilic esophagitis, we decided and have stated that we won't bring forward this asset in that space commercially. Again, because of the bars that we need to meet from a development and from a commercial perspective. But I think if you then think about SOTYKTU, we continue to develop and are very excited, as I mentioned, about the programs. For example, we just laid out some data and disclosed data at AAD this past weekend in psoriatic arthritis. And as I mentioned, we're highly anticipating the data that will come forward in our 2 lupus and our Sjogren's studies. These are areas of high unmet need, areas that we've been in, in the rheumatology area and areas that we think can meet those criteria. So I think as we go forward in development, we're really looking forward to continuing to develop where we can meet the high bars that we set out for success and where we have a competitive advantage. I think the underlying commonality here, though, is to continue to develop in areas where there's a high unmet need and where we can bring meaningful medicine to patients.

Very helpful. Excellent. And so turning to Cobenfy. Could you talk about the efficacy bar in adjunctive schizophrenia? And what is the Phase III trial powered to demonstrate?

Yes. So thanks for the question, Dave. We're excited, as I mentioned, about the readout that's coming forward with the ARISE study of Cobenfy an adjunctive schizophrenia. I mean, just to step back, this is really founded on the mechanism of action of Cobenfy. It's novel M1, M4 dual agonism as well as the safety and tolerability profile that we've seen coming out of the emergent program in schizophrenia. And so when we think about this given the unmet need and even though we have not publicly disclosed the statistical plan or the powering assumptions associated with the ARISE because of the unmet need, we believe that really the ability to show any benefit that is additive and demonstrable on top of the background therapy in reducing symptoms of schizophrenia will be important for patients and meaningful for patients. I think when you add that on top of the fact that if you step back with schizophrenia, there still remains such an unmet need. It's been reported that up to 75% of patients with schizophrenia are off of their antipsychotic by 18 months and you think about the challenges here, we even see D2 agonists being combined, even in spite of the lack of clinical data or regulatory approval, there's an unmet need here. And I think so importantly, along with the efficacy that we're looking for. We're also looking for ability to add a complementary mechanism because of the favorable safety and tolerability profile we've seen from Cobenfy thus far that doesn't overlap. And so it's for those reasons that we think Cobenfy is an attractive agent as a potential adjunct.

Very helpful. So turning to AD psychosis. Why is Cobenfy being studied 3 times a day in AD psychosis when it's been studied BID and other indications? And then I know that you're in the process of bridging to BID dosing. Will that change the side of profile at all?

Yes. Thanks for that question. We're very excited, as I mentioned, about Cobenfy and it's our program in AD psychosis, where there's huge unmet need. If you step back, Dave, the original studies of xanomeline in patients with Alzheimer's disease that were reported back in the late 1990s, we're actually with xanomeline studied 3 times daily. But I think another consideration that you're alluding to is the fact that if you step back elderly patients, in general, may be potentially more susceptible or more sensitive to potential side effects generally with medicines overall. And so when we took data that we looked at from a study in healthy elderly volunteers, and we looked at our program, that is when you think about the potential for sensitivity, that's the reason why Cobenfy is being dosed in TID administration to optimize the tolerability profile there. That said, so we are doing our ADEPT 1, 2 and 4 studies with Cobenfy dosed in TID fashion, but we have plans to bring forward BID dosing in the Alzheimer's disease indications as we move forward with the Cobenfy program, Dave.

And so when will you have clarity on the BID dosing? Or is that -- meaning -- I mean, obviously, you already have the IV dosing, but is there any sort of transition that you plan for commercialization from TID to BID?

So a few things there, Dave. I think we are prepared to move forward with TID dosing in Alzheimer's disease psychosis. But we are actively looking at plans again to introduce BID dosing in future studies as we move forward in our Alzheimer's program. And as you're aware, thinking about Alzheimer's disease and agitation and in cognition as well as what work that we do in psychosis. So we're very excited about the programs ahead.

Yes. I was -- it was just sort of more so my curiosity. I mean, clearly, with Alzheimer's patients, they're going to be administered the drugs by a caregiver anyway. They're not left to remember to take their drugs either twice a day or 3 times a day, anyway.

And that is an important consideration, Dave. When you think about the population, especially those with more advanced Alzheimer's disease, we do recognize that, that oftentimes these patients are supported by caregivers in terms of their medicines. And so we think that, that TID dosing is something that would be an important option here. Of course, we continue to look forward, as you mentioned. And as I've just mentioned about looking forward how to continue to simplify regimens.

Got it. And just remind us what are those side effects that you're hoping to minimize or see acceptable results in?

Yes. So we are doing a number of things to address and optimize the tolerability profile associated with Cobenfy. Inherently, this is well described with the Sanctura label, of course with Trospium and the potential anticholinergic effects that have been described, of course, in the USPI. But -- what we are doing specifically is, for example, we talked about TID dosing. In addition, what we've done is we've optimized the ratio of xanomeline to Trospium. So it's actually 10:1 in Alzheimer's disease studies versus the 5:1 ratio in patients with schizophrenia. Again, to optimize the tolerability of Cobenfy. And then finally, when you look at the titration regimen that we're using in ADEPT, we are titrating slower than what we did in the emergent program. So these 3 things, in addition to what you said about the support in this patient population, all give us confidence in the profile of Cobenfy. And I think importantly, of course, in a blinded way, what we've seen thus far continues to give us encouragement.

Excellent. That's great. So just looking forward, so there are 4 planned Phase III programs for Cobenfy if I have that right that's bipolar disorder, Alzheimer's cognition, Alzheimer's agitation and Autism. It seems that 2, in particular, a very high risk, so specifically Alzheimer's cognition and Autism, right? Because there's really virtually nothing approved. I mean obviously, there's some recently approved Alzheimer's drugs for cognition, but the benefits are quite marginal. So could you just comment on what I stated and just why you are pursuing those 2 high-risk indications?

Yes. We're -- one of the things about Cobenfy that we're excited about is owing to its mechanism that is mechanism as an M1, M4 dual agonist is that it has the potential to impact and benefit patients across a wide range of different indications. And so when you think about that, we're excited about those 2 applications, specifically as well. If you think about autism spectrum disorder, a disorder where there's a great deal of unmet need. It's a population where there are a few approved therapies but with side effect profiles that would cause concern, particularly in that patient population. There's some evidence to suggest that modulation of the dopaminergic pathways would be important in trying to address some of the important symptomatology associated with autism spectrum disorder, irritability or agitation or other symptoms such, and we do see that translation in agents -- the few agents that actually were studied initially in, say, schizophrenia to that -- to autism spectrum disorder. But we think it's important to try to build options here. And we think that Cobenfy given what we've seen in the emergent program, given its mechanism and its safety and tolerability profile with the science will actually give us the potential to offer another option for patients with ASD. I think with cognition, it has been great to see advances in the area with disease-modifying therapies, but there still remains a great unmet need. And that plus the challenges with cholinesterase inhibitors and such, really make this an important area with cognition. We think with the mechanism of Cobenfy, particularly the M1 agonism, which is putatively thought to have an important effect on cognition, as well as the data that we saw from, again, the [indiscernible] study published in the late 1990s, that evidence in patients with Alzheimer's disease showed benefit of xanomeline in a number of different aspects of Alzheimer's disease. One being cognition, specifically as well as agitation and psychosis. And so we are looking forward to bringing these studies forward in AD cognition because of this and helping to build on the evidence and as well as the options in Alzheimer's disease. And so we're looking forward to that.

Excellent. Thank you. So then pivoting to cardiovascular. Milvexian offers tremendous potential in 3 potential blockbuster indications. And I'd like to ask about all 3. So just at a high level, drug efficacy is typically correlated with side effects. And so there is the expectation or the target product profile of delivering similar efficacy to Eliquis with far less bleeding risk. And so just on the efficacy front in AF, how is that possible? And I guess, I believe that you're not quantifying the magnitude of Factor XIa inhibition. So how would you even know how -- to what degree you need to inhibit Factor XIa, whether it's 98% or 92% to match Eliquis?

Yes. Thanks for the question, Dave. And I think a lot to unpack there. I mean if you step back with Librexia AF, we are very excited about this program that we are bringing forward with our alliance partners, Johnson & Johnson. We are very pleased with the way that program has progressed. As you know, we increased the sample size to 20,000. We're nearing completion of enrollment. And in fact, we expect to be able to close enrollment for Librexia AF at the end of this month. I think as you think about the efficacy, for example, relative to Eliquis and some of the assays that you alluded to, I think if you step back our confidence in milvexian is really borne out of a number of different lines of evidence that have converged together. I mean, if you think about the genetics, we know that patients who have a genetic deficiency in Factor XI, that is hemophilia C, patients actually have a decreased risk of stroke in venous thromboembolic events, but not associated with the serious bleeding that you would see with other hemophilias. And we've confirmed that with models preclinically as well as in assays that show that milvexian behaves the way we would want and expect it to when we look at standardized Factor XI clotting activity assays or a PTT for that matter. But I think the most important thing that gives us confidence here is the clinical data. I mean we conducted 2 large Phase II clinical outcome studies in Phase II and very complementary patient populations and on different backdrops of treatment. That is, one is monotherapy and TKR total knee replacement. And the second, in combination with anti-platelet therapy in secondary stroke prevention. When we think about the TKR data, in particular, this is a well-validated surgical model that was the basis for how Eliquis and rivaroxaban were developed in atrial fibrillation. And what we saw there importantly was that there was -- and we studied milvexian over a 16-fold dose range. We saw a dose response for efficacy with efficacy at 50 milligrams BID and above, that was superior to the standard of [indiscernible]. But we didn't see a dose response and safety. In fact, we didn't see any major bleeding events in that TKR study, and we didn't see that dose response. And that's important because it helps to corroborate the thinking that you can decouple the efficacy associated with this mechanism from the bleeding liability, and it goes all the way back to where factor XI sits in the coagulation cascade. It really is the belief that factor XI is important in sort of consolidation and propagation thrombus but not critical or pivotal for really the kind of good clotting that you need that is the hemostasis when we're bleeding acutely. And so all of these things have allowed us to feel confident importantly about the dose we selected for Librexia AF the 100-milligram BID dose because we think that's important because really, again, against an active comparator, and Eliquis has been a great advance. We specifically chose that dose based on those lines of evidence and the modeling that was done, and we described in our design paper to support milvexian in that indication specifically.

Excellent. And then turning to secondary stroke. So Bristol chose 1/4 of the dose that it studying an AF for SSP. Can you just discuss the confidence that you have in that trial succeeding given that dose selection, meaning why 50 in a patient population that probably has different comorbidities, maybe it should be 30 and some, maybe it should be 65 and some, you chose 50 for a very large trial. And then what magnitude of benefit would be clinically relevant and secondary stroke?

Yes. Thanks for the question, Dave. I think this is, again, the benefit in what we think sets us apart from other programs and having clinical data in Phase II that we can draw on. And so in Phase II, we were able to study milvexian on top of anti-platelet standard of care. And what we saw was an early dose response followed by a plateau and from doses of 25 milligrams BID to 100 milligrams BID, we saw about a 30% relative risk reduction in clinical ischemic stroke events. And it's important that we were able to see this across the dose range. Importantly, what we didn't see was a dose response in bleeding. And again, this is something that sets apart. We hope the profile of milvexian versus the DOACs or the Factor Xa inhibitors because we didn't see any fatal bleeding, we didn't see any evidence of a dose response in symptomatic intracranial hemorrhage. I think if you think about this, and if you step back, the issues with DOACs in these areas is the inability to combine, say, Factor Xa inhibitors on backdrop of anti-platelet therapy because of the risk of bleeding, not because they might not provide efficacy benefit in preventing ischemic events. And then the final thing I'd say about 25 milligrams BID is again, you can corroborate data because we had 25-milligram BID data in the TKR study, where you actually saw comparable efficacy to enoxaparin. And so again, not -- it's something where you have to show efficacy. And when you think about the bar that we're looking for, we do want to see a significant decrease in stroke following a stroke or TIA. But we also want to see that this approach does not lead to a significant increase in the most consequential series of bleeds that is fatal bleeds or symptomatic intracranial hemorrhage.

Excellent. And then obviously, if asundexian succeeds late this year in secondary stroke, that would be a positive, right, in terms of validation. But I guess in the event that it disappoints what should we be focused on? Or how should we think about that? If that asundexian trial fails, I know it's smaller than Bristol's, but just curious.

Yes. Thanks for the question, Dave. We are really excited and confident about how we try to optimize our Librexia SSP study both with respect to the inclusion criteria, simplified criteria, we're looking to get a broad range of patients with stroke into our study. We're excited about the dose selection, which we just discussed. And then finally, the sizing of the study, where we're looking to enroll about 15,000 patients in our study. And so there are differences. And there are differences in the molecules, the regimens. Of course, it's always hard to make cross-trial comparisons. I think that said, we're going to be interested in looking at the efficacy and safety readouts when this study does come out. And we'll try to digest the data as it comes out, likely in sequence. But I think it's important that because of all those reasons, we also need to be careful about making cross-trial comparisons when those data do read out.

Very good. And then in ACS, so I guess just at a high level, what gave Bristol confidence to advance milvexian into Phase III. So I asked the question because Bayer had conducted a study in, I think it was hard fit. No. I forget, what was the study that they didn't specifically study ACS in Phase II.

They did have a Phase II study in ACS as well as, okay, I don't know the secondary...

Yes. So yes, I think they titled that AMI or something, but effectively ACS. So after studying that drug in that trial, they decided not to proceed into Phase III. On the flip side, Bristol never conducted a trial in Phase II in ACS, but decided to go into Phase III. So could you just comment on that, please?

I think -- when we look at our ACS indication, we're excited and that excitement is founded in large part because, again, going back to the clinical data that we saw in our SSP study. Again, being able to show a clinically meaningful benefit across a range of doses with the bleeding profile that we saw was important. And I think that as you think about the mechanism and the pathophysiology of secondary strokes, we see that there's a good deal of similarity to the mechanisms that are in play with acute coronary syndrome. That is a thrombus and plaque and plaque rupture, leading to ischemic events. These are reasons why we think because of the profile of milvexian, what we've seen on top of anti-platelet standard of care in the secondary stroke prevention that there's a good deal of belief to be able to translate this into the ACS population. And I'll just close on the fact that, again, we've seen that the addition of Factor Xa inhibition can lead to reduction of events in the acute arterial setting. The challenge here is one of increased bleeding. We're extremely excited about milvexian given what we've discussed and looking to see that we can deliver efficacy but without increase in serious bleeding in these populations.

Excellent. Well, we are over time. I have 12 more questions, but we are not getting to them today. So I'm glad we covered some big drug opportunities. Really appreciate you being here.

Thank you so much, Dave.

Thank you again.