Terrific. We are just about in time, so let's keep moving and kick off with our next session. Bristol Myers, I'm very excited to have Christian Massaseki, CMO, and Chuck Trellano, SVP and Head of IR. Welcome both. Thank you for being here.

Great to hear.

So, Christian, I know that there's a lot to talk about, but maybe we can start at 10,000 feet at a high level. You know, 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 and 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 three, four things that I spent, 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 risk all the studies, the big pivotal studies, as much as we can. Because, you know, phase three studies are set in times and during the conduction condition can change. And phase three studies can fail for different reasons. Operational reasons, study design reasons, patient populations. And not necessarily you can change the science that is underneath a phase three, 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 risks 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. So you can do that. So this gave me confidence that for the next wave of catalysts, 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, for instance, 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, it is a corporate level, to integrate our programs and our drugs into TA 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 on 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 Cobenphy, we wanted to be back into this space, but we need to rebuild the unit, and this requires 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 that is exciting. I'm very happy about the progress we did.

Well, that's great, Christian, and maybe we can start peeling away at the onion at a few of these, you know, these programs, starting with oncology at a high level. I mean, we've just come off a VASCO, very dynamic conference this year, lots of focus again, specifically from Bristol's perspective on the PD-L1, PD-L1, VEGF-Pi specific class. So, you know, I guess I want to start with just hearing your updated thoughts on Pumidamig, you know, in the context of the very encouraging data that was presented at ASCO and overall thoughts on the PD-1, PD-L1 VEGF class, particularly given the debates around Akizo's Harmony 6 trial and the issues that were raised by the discussant on the stage when the data was presented. That fuels some investor debate. Are those really substantial concerns, or is this just skeptics trying to poke holes in the data?

It was a good ask. Thank you for bringing it up. It was my first ask in BMS, but it was an exciting ask because I think as BMS, we were able to move from a lot of presentation focused on to presentations showing the next portfolio. Pumitamig was one. We had the cell modes. We can talk about that. We have our ADC isabren. We have some data also. We have Pyramid V. So, very exciting because we start to show that there is a portfolio. And in oncology, in solid tumor, in hematology, it starts to be, there is substrate. Right. PD-1 VGF, 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. You start to see consistently better response rates, consistently PFS benefit, and I start to see some OS data with all the limitations that studies conducting in one specific geographical region may have. Looking at our data, I am very pleased with 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 and no 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 on 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 Pembrol 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 a response rate in the context of a small data set, but numerically much better than what you expect with Pembroke 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 VGF inhibition can be better than giving the two antibodies as a combination. And this is because PD-L1 and VGFA is in the microenvironment, tumor microenvironment, and when the drug is binding, a cluster is forming, and the cluster, the drug and the two 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 the same experiment with 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 two mechanisms as a bispecific can be more selective. Ultimately, VGF inhibition helps PD-1 internalization and can help actually to increase the activity of PD-1 because it can reinvigorate this 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 VGF can open up other indications on colon cancer. The program, we are doing this in collaboration with BioNTech. The program is moving very, very nicely. We have seven pivoter studies. We have more than 20 combo studies because the next step is not only delivering monotherapy or combo with standard OCEA, but it's building the next level of regimens with a novel, novel combination. And here the rest of our portfolio step in, combo with IDC, combo with other diseases.

And I want to talk about that. But one thing just maybe on the program itself, you know, it seems to me that 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 really sort of pressing the accelerator on the speed at which their own programs are moving. For example, Merck said that they are now phase three ready, which I think surprised some people. So, you know, what are the next milestones we should be looking for from Pumid and Meg in terms of just monitoring the progress of your own program?

As I told you, we have 20 studies ongoing. Some of them will take a little bit longer, but a lot of them are Phase I, B, 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. You know, and again, in a moment in which you will see some of the combo data merging, it means that probably the next steps as a pivotal study is going to happen.

Okay. Well, let's pivot from there to, you know, a theme you already brought up, novel novels, ADCs, another big focus at ASCO, your partner for Isabren, presented China phase three data for breast and esophageal cancer. So both met their dual primary endpoints of PFS and OS. So give us an overview at a high level on the global development plans 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 and radiotherapy are working. The problem is the lack of selectivity and specificity. ADCs and radioligands are a better way to deliver these two modalities. So isobren is a very nicely engineered drug because, first of all, it's a bispecific ADC. It's an EGFR R3 ADC. EGFR and R3 are two targets that touch most of the solid tumors. And this drug is specifically higher affinity for EGFR with a very stable linker and short of 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 it is injected, it 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 3 as you mentioned there are three phase 3 positive studies it's not anymore one and in different indication esopharyngeal carcinoma we presented we presented esophageal cancer and triple negative breast cancer later line versus standard chemotherapy. And China only data sets in my phase three. And, you know, the activity is remarkable, especially because you get the PFS and OS in both trials with very important hazard ratios. In triple negative breast cancer, the PFS hazard ratio is 0.29 from 3.5 months to 8 months. And the OS, the hazard 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 DAR-8 ADC. So I think, but the discontinuation rate is very low. And in the global data sets, because now we have global ongoing studies, phase one, two, and we have three phase three studies globally ongoing in EGFR, lung cancer, mutant, in triple negative breast cancer, in 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 pumetamib, for instance, or other player in our drug. So I'm excited about this one.

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

Talking about iberdomide, let me start with the platform. I think BMS were able to leverage and to expand cell gene platform on protein-targeted degradation. I think this is a very powerful platform that is delivering important drugs that can degrade proteins like Icarus or Iolus in myeloma and lymphoma, but also other targets that are really key for the cancer cells. BCL-6 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. So the platform is delivering. We have 11 drugs in clinic, some like Ibermezzi, but also Golcadomide in Phase III. And 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 in standard of care across Onco and Im. Iberdomide specifically, Pedufa did, 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 data said that we have to show how combinable is this drug and how it can be integrated in the standard of care. This is both for iberdomyde and mesygdomyde. Our cell modes being oral drugs can be added on top of standard of care. And Excalibur is on top of Dara and Dexa. At ASCO we show data in the context of a quadruplet 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 deep end of the response, the MRD response with Iberdomide alone. So it speaks on the quality of these assets, how potent they are, how selected they are, and how they can be integrated in the treatment that is becoming more and more fragmented of myeloma as an add-on. Or iberdomide next registrational study will be in post-transplant versus revlimid as monotherapy.

And then maybe just quickly on mesectomite as well, those phase 3 data appeared encouraging in relapsed refractory multiple myeloma, but interestingly, the data was presented on the back of J&J's Majestic 9 study, which was also impressive. So maybe taking a step back, you know, we're hearing some conversations focused on choosing between CAR-T and bispecifics in the second line. So where do you see this mesectomite fitting into the multiple myeloma treatment paradigm?

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 cell modes will fundamentally replace Revlimid apomalidomide, because there are better drugs, more selective engineers for that. and their combinability can be integrated in the current standard of care but also the future standard of care. Actually, just last week we published two papers in blood showing how mesectomide 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 cell modes in the treatment of myeloma.

Okay, and then Christian, maybe one last on oncology before we move on. Just to, you know, 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 navilimethostat and is a pre-MT5 working NEMTAP 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 monotherapy and lung and pancreatic cancer response rate are holding 34% in lungs, 18% monotherapy. But the durability is very good. Not only the response the durability of stabilizations. The drug is doing what it's supposedly to do. Then what I really even like more is the combinability. The safety profile and avalometostat is very good. It's very mild. We have three pillars. Combo with chemo. We are in phase 2, 3. In pancreatic cancer, germabraxen. We know we can combine. Soon we're going to be in phase 3. And in lung cancer, we're platinum doublet. This is the first entry. And then we are combined with pumetamig because it makes sense combining with PD1VGF, plus or minus chemo. And the last is the combination with the PARAS. The data you have seen yesterday, very important also for me because the risking, the combo, and we know, we knew that there is a potential synergism of these two pathways, and actually this preliminary, very preliminary, but promising data showing that I'm very excited about the opportunity. And, you know, 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 of that, we didn't have anything.

Okay, well, maybe we can pivot to Cardio. And, you know, 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 start there.

Yeah. The study was designed on the outcome of a very solid Phase II study in which ran in totality replacement as good surrogate for outcome, testing a very wide range on 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 it's a strategy against a Pixaban. 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 selected, 100 milligrams 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 non-inferiority for events, strokes, and thrombobolic events, and then a superiority for bleedings, measured bleedings, and non-measured bleeding clinically relevant. I'm blinded. No good news in my view. DMC continue to monitor the study in a regular and regular way. we have we 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, Christian, you know, on the bleeding side, what is the expected magnitude of superiority in your view to drive a meaningful displacement of eloquence?

I think, Chuck, you can step in if you want.

You've been waiting patiently.

To me, what I can tell you is that today there are at least 30%, 40% of patients on eloquence that because of bleeding risk or because they are experienced bleeding are not receiving eloquence or not receiving eloquence at the right dose. So they are 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 measured bleeding clinically relevant in more patients are both clinically meaningful. We will see the outcome of the study. But Jack, what do you think?

Yeah, I think the conversations we would have naturally pre-marketing 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'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 Christian's point about the 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 three 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, Christian, back to you, how do you think about the commercial implications of hitting your non-inferiority margin but with a point estimate or hazard ratio of maybe slightly above one?

Will be the totality of the data. I think we can speculate, it's 1.0, 1.05, we can 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 11 inhibitors, Malvexia, and also other drugs are showing consistently to be beneficial on the bleeding rate. So I believe we are on track with that trial.

Let's see.

The good news is not far away. So we don't have to wait too long.

Let's move to Neuro. Let's talk about Kobenfi. Maybe just, you know, open-ended question. Give us your latest framing and update ahead of the ADEPT 2, 1, 2, and 4 trials.

Yeah, the COBENFI is a big area of focus that we are having. As I was telling you, we are building. We are now built a good infrastructure, a good unit in Europe. I'm very pleased that we are progressing the program. Consider the COBENFI, we have 12, 13 pivotal studies ongoing. So it's a very large program because there are four studies in psychosis, Alzheimer's psychosis. There are three studies in bipolar, two studies in agitation, in cognition for Alzheimer's, and then autism and irritability. So it's a large program. We have multiple shots on goal. Psychosis is the first potential readout for the product. but the base case is having at least two positive studies to be able to go and try to seek for an approval. As you know, ADAPT-2 and ADAPT-4 are similar, even if there are differences, because ADAPT-4 is a biomarker-selective population. We want it to have a more homogeneous patient population. It's based on tau plasma assessment. Of course, this increases a little bit, more than a little bit, the screening failures, because we want a patient that is positive, but it's progressing well. And ADEPT 2 now restarted. We learned from ADEPT 2 executional e-cups that we had, and now I am full confidence how the program is delivered across. ADEPT 1 is a different study, because, you know, it's a study in which we have not assessing like in ADAPT 2 and 4 a time-bound score that is measuring hallucination and delusions, baseline and after 14 weeks, but we are recruiting psychotic events. The patient starts with a raninocobemphi and then is randomized to continocobemphi or placebo, and then the patient experiencing a psychotic event 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 recruitment, how we are recruiting events. So we will inform why we will conduct the study. We are on track of how we got it 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 Kobenthi program, which ones?

I think psychosis is very anchored on three factors. The first one, xanomaline showed 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 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 that we didn't disclose. So I think the ADAPT program is anchored on this. Bipolar, that is the next coming, next year, I think is also anchored on similar symptoms because we are treating mania in these patients that are experiencing with bipolar underlying disease. So I believe that this is also an area where CoBENFIC can bring benefit. Agitation, if you think, is very linked to productive symptoms. So in my view, it is also an area that can be beneficial. Condition is different. Condition is different because while the prior trials are anchored more on for inhibition, condition is more M1, muscarinic 1 receptor inhibition. So it's a little bit different concept. Overall, I believe that co-benf is a drug that in schizophrenia is bringing a lot of benefit to the patients. And, you know, it's a drug that will help 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 in schizophrenia give us confidence. Then I want to build on Cobenphi, because Cobenphi is an anchor, but there is substrate below Cobenphi. We are building a very strong Alzheimer's portfolio. We have an anti-tau antibody, and we have a famagal drug that can work both in MS plasticity but also in agitation that are in phase two. 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 Admiral Perrin, but before I do that, Chuck, you've been waiting patiently, and I just want to maybe, you know, give you the opportunity to highlight just sort of business trends, anything as we're closing the quarter that you want to touch on. You know, 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?

Yeah, business continues to do well. The growth portfolio is delivering. executing on the pipeline obviously as you mentioned and spoke with christian 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's no hesitation on business development in terms of the question we get often are you waiting to see all the phase three 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've 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.

That's great, Chuck. Christian, maybe back to you in the interest of time. We just have a couple of minutes left. I have two topics I did want to talk about. I'm going to let you choose. I don't know, Parent and Kamsayos, where do you want to go? Amit Parent. Let's talk about that. What, you know, levels at us?

I like the target. LPA1 is a novel. And, you know, pulmonary fibrosis is a nasty disease. There are not so many options. Having a drug that can bring a novel target is very helpful. It's 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 two, you know the phase two, The phase 2 was positive in IPF and PPF. The phase 3 was very, very much run to try to replicate the conditions of the phase 2. This is the secret to have, most of the time, a good outcome in phase 3. In addition, I think we were able to integrate an higher dose. That, in my view, helps. Because we have seen a dose relation in efficacy between 30 and 60. 60 was actually the dose, but then we took the risk to put 120 into the phase 3. The DMC assessed 120 in a safety run-in and efficacy run-in and gave the green light. Then the studies have been conducted, more than 1,200 patient studies, each one of them, two doses, 120, 60 placebo, and the good news is that we didn't have any safety signal in terms of hypotension, syncopal episodes. So this is good. And, of course, you know, we will see when we unblind the data, but we have two 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 busy.

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 two studies a few months apart. So there's two separate studies, but, yeah, potentially the regulatory strategy can be one.

Christian, 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 thank you