Great. 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. 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. Just by way of introduction, I've been at Bristol Myers Squibb 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. Currently, I head immunology, cardiovascular, and neuroscience development. Really, Dave, that's where I allocate most of my time in going ahead. Excellent. Excellent. Great. With respect to the Phase 3 trials that you're most excited about, and before we go into the specific therapeutic categories, could you talk about the big cards that are turning over over the next couple of years? Yeah. 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 two years across the therapeutic areas. I mean, just to touch on a few highlights in cardiovascular, we're looking forward to the readout of our Odyssey study in 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. We are 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. 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. 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 a near-term readout for Cobenfy in the ARISE study in Phase 3 in patients in adjunctive schizophrenia. This is an area, again, where there's a high degree of unmet need. We're looking forward to Cobenfy readout here. I think it's exciting, particularly, Dave, because Cobenfy, as an M1, M4 novel dual agonist, really represents the first novel mechanism for patients in schizophrenia in decades. This is going to be followed by data later on in this year from the ADEPT-2 study. Really exciting to see what Cobenfy's potential is in Alzheimer's disease psychosis, an area where there's no approved therapies. That will be followed by data readouts in 2026 from ADEPT-1 and ADEPT-4. Finally, in the immunology space, we're highly excited about Admilparant, our novel first-in-class LPA1 antagonist. We are looking forward to data in 2026 in patients who have idiopathic pulmonary fibrosis, followed by data in progressive pulmonary fibrosis. Again, an area where there's really not great treatments and an area where there's high unmet need. With Sotyktu readouts in 2026, two studies in SLE followed by a readout in 2027 with Sjögren'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. Really an exciting time for Bristol Myers Squibb. Excellent. That's great. Maybe before I go into some of the more specific questions on individual drugs, I did want to ask a high-level question. 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 to Sotyktu, but that hasn't happened. 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, just how does that inform your thinking and R&D as you work with your commercial colleagues on development Phase 3 projects? Yeah. Thanks for the question, Dave. You know, as we've stated, you know, dermatology is an extremely competitive area. It's highly managed with payers. There's a lot of therapies that are available. When we step back and we think about how we are and we will continue to develop, you know, 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. 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 two criteria. Even when you think about Phase 3 data and eosinophilic esophagitis, you know, 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. I think if you then think about Sotyktu, you know, 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. As I mentioned, we're highly anticipating the data that'll come forward in our two lupus and our Sjögren'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. 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 medicines to patients. Very helpful. Excellent. Turning to Cobenfy, could you talk about the efficacy bar in adjunctive schizophrenia and what is the Phase 3 trial power to demonstrate? Yeah. Thanks for the question, Dave. You know, we're excited, as I mentioned, about the readout that's coming forward with the ARISE study of Cobenfy in adjunctive schizophrenia. I mean, just to step back, this is really founded on the mechanism of action of Cobenfy, its 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. 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 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. You know, it's been reported that up to 75% of patients with schizophrenia are off of their antipsychotic by 18 months. 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. I think so importantly, along with the efficacy that we're looking for, we're also looking for the 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. It is for those reasons that we think Cobenfy is an attractive agent as a potential adjunct. Very helpful. Thank you. Turning to AD psychosis, why is Cobenfy being studied three times a day in AD psychosis when it's been studied BID in other indications? I know that you're in the process of bridging to BID dosing. Will that change the cytophobic profile at all? Yeah. Thanks for that question. We're very excited, as I mentioned, about Cobenfy and 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 were actually with xanomeline studied three times daily. I think another consideration that you're alluding to is the fact that, you know, if you step back, elderly patients in general may be potentially more susceptible or more sensitive to potential side effects generally with medicines overall. 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, 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. When will you have clarity on the BID dosing or is that meaning, I mean, obviously you already have BID dosing, but is there any sort of transition that you plan for commercialization from TID to BID? A few things there, Dave. I think, you know, 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. As you're aware, thinking about Alzheimer's disease and agitation and in cognition, as well as what work that we do in psychosis. We are very excited about the programs ahead. Yeah. It was just sort of more so my curiosity. I mean, clearly with Alzheimer's patients, they're going to be, you know, administered the drugs by a caregiver anyway. They're not left to remember to take their drugs either twice a day or three times a day anyway. That is an important consideration, Dave. When you think about the population, especially those with more advanced Alzheimer's disease, we do recognize that oftentimes these patients are supported by caregivers in terms of their medicines. We think 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. Just remind us, what are those side effects that you're, you know, hoping to minimize or see, you know, acceptable results in? Yeah. So, you know, we are doing a number of things to address and optimize the tolerability profile associated with Cobenfy. You know, 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. 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 to 1 in Alzheimer's disease studies versus the 5 to 1 ratio in patients with schizophrenia, again, to optimize the tolerability of Cobenfy. 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. These three things, in addition to what you've said about the support in this patient population, all give us confidence in the profile of Cobenfy. I think importantly, of course, in a blind way, what we've seen thus far continues to give us encouragement. Excellent. That's great. Just looking forward, there are four planned Phase 3 programs for Cobenfy, if I have that right. That's bipolar disorder, Alzheimer's cognition, Alzheimer's agitation, and autism. It seems the two in particular are very high risk, specifically Alzheimer's cognition and autism, right? Because there's really virtually nothing approved. I mean, obviously there's, you know, some recently approved Alzheimer's drugs for cognition, but the benefits are quite marginal. Could you just comment on what I stated and just why you are pursuing those two high-risk indications? Yeah. One of the things about Cobenfy that we're excited about is owing to its mechanism, that is, its 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. When you think about that, we're excited about those two applications specifically as well. If you think about autism spectrum disorder, you know, a disorder where there's a great deal of unmet need, you know, 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. You know, there's 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. You know, we do see that translation in agents, the few agents that actually were studied initially in, say, schizophrenia to autism spectrum disorder. We think it's important to try to build options here. 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, you know, it has been great to see advances in the area with disease-modifying therapies, but there still remains a great unmet need. That, plus the challenges with, you know, 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 beautifully thought to have an important effect on cognition, as well as the data that we saw from, again, the Bodick study published in the late 1990s, you know, 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. You know, we are looking forward to bringing these studies forward in AD cognition because of this and hoping to build on the evidence as well as the options in Alzheimer's disease. We are looking forward to that. Excellent. Thank you. Pivoting to cardiovascular, Milvexian offers tremendous potential and three potential blockbuster indications. I'd like to ask about all three. At a high level, drug efficacy is typically correlated with side effects. You know, there is the expectation or the target product profile of delivering similar efficacy to Eliquis with far less bleeding risk. Just on the efficacy front in AF, how is that possible? I guess I believe that you're not quantifying the magnitude of Factor XIa inhibition. How would you even know how, you know, to what degree you need to inhibit Factor XIa, whether it's 98% or 92% to match Eliquis? Yeah. Thanks for the question, Dave. 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. You know, we are very pleased with the way that program has progressed. As you know, we increased the sample size to 20,000. You know, we're nearing completion of enrollment. 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 born 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 11, that is hemophilia C, patients actually have a decreased risk of stroke and venous thromboembolic events, but not associated with the serious bleeding that you would see with other hemophilias. You know, 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 11 clotting activity assays or APTT for that matter. I think the most important thing that gives us confidence here is the clinical data. I mean, we conducted two large phase II clinical outcome studies in phase II in very complementary patient populations and on different backdrops of treatment. That is, one is monotherapy and TKR, total knee replacement. The second, in combination with antiplatelet therapy and 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. 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 b.i.d. and above that was superior to the standard of care in enoxaparin. We did not see a dose response in safety. In fact, we did not see any major bleeding events in that TKR study, and we did not see that dose response. You know, that's important because it helps to corroborate the thinking that you can decouple the efficacy associated with this mechanism from the bleeding liability. It goes all the way back to where factor 11 sits in the coagulation cascade. You know, it really is the belief that factor 11 is important in sort of consolidation and propagation of 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. All of these things have allowed us to feel confident, importantly, about the dose we selected for LIBREXIA AF, the 100 milligram b.i.d. dose, because we think that's important because really, again, against an active comparator, and Eliquis has been a great advance. You know, we specifically chose that dose based on those lines of evidence and the modeling that was done and that we described in our design paper to support Milvexian in that indication specifically. Excellent. Turning to secondary stroke, Bristol chose a quarter of the dose that it is studying in 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 in some, maybe it should be 65 in some. You chose 50 for a very large trial. What magnitude of benefit would be clinically relevant in secondary stroke? Yeah. Thanks for the question, Dave. I think this is, again, the benefit and what we think sets us apart from other programs in having clinical data in phase II that we can draw on. In phase II, we were able to study Milvexian on top of antiplatelet standard of care. What we saw was an early dose response followed by a plateau. You know, from doses of 25 milligrams b.i.d. to 100 milligrams b.i.d., we saw about a 30% relative risk reduction in clinical ischemic stroke events. It's important that we were able to see this across the dose range. Importantly, what we did not see was a dose response in bleeding. This is something that sets apart, we hope, the profile of Milvexian versus the DOACs or the Factor XIa inhibitors, because we did not see any fatal bleeding and we did not 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 XIa inhibitors on backdrop of antiplatelet therapy because of the risk of bleeding, not because they might not provide efficacy benefit in preventing ischemic events. The final thing I would say about 25 milligrams b.i.d. is, again, you can corroborate data because we had 25 milligram b.i.d. data in the TKR study where you actually saw comparable efficacy to enoxaparin. It is something where you have to show efficacy. 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. We also want to see that this approach does not lead to a significant increase in the most consequential serious of bleeds, that is, fatal bleeds or symptomatic intracranial hemorrhage. Excellent. Obviously, if asundexian succeeds late this year in secondary stroke, you know, that would be a positive, right, you know, in terms of validation. 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 is smaller than Bristol's, but just curious. Yeah. Thanks for the question, Dave. You know, we are really excited and confident about how we try to optimize our Librexia SSP study, both with respect to the inclusion criteria, the 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. Finally, the sizing of the study where we're looking to enroll about 15,000 patients in our study. There are differences. There are differences in, you know, the molecules, the regimens. Of course, it's always hard to make cross-trial comparisons. I think that said, Dave, we're going to be interested in looking at the efficacy and safety readouts when this study does come out. You know, we'll try to digest the data as it comes out, likely in sequence. I think it's important that, you know, because of all those reasons, we also need to be careful about making cross-trial comparisons when those data do read out. Very good. In ACS, I guess just at a high level, what gave Bristol Myers Squibb confidence to advance Milvexian to Phase 3? I ask the question because Bayer had conducted a study in, you know, I think it was, you know, heart failure. No, I forget. What was the study that they did not specifically study ACS in phase II? They did have a phase II study in ACS, as well as in AF and in secondary stroke programs. Yes. Yeah, I think they titled it AMI or something, but effectively ACS. After studying that drug in that trial, they decided not to proceed into Phase 3. On the flip side, Bristol never conducted a trial in phase II in ACS, but decided to go into Phase 3. Could you just comment on that, please? Yeah. I think when we look at our ACS indication, we're excited. 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 clinically meaningful benefit across a range of doses with the bleeding profile that we saw was important. 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, say, 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 antiplatelet standard of care and the secondary stroke prevention, that there's a good deal of belief to be able to translate this into the ACS population. I'll just close on the fact that, again, we've seen that the addition of Factor XIa 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. We are over time. I have 12 more questions, but we are not getting to them today. I am glad we covered some big drug opportunities. Really appreciate you being here. Thank you so much, Dave. Thank you again.