Bristol-Myers Squibb Company ($BMY)

Terrific. We are just about at time. So let's keep moving and kick off with the next -- 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. We've noted that Bristol has been performing very well from a commercial execution perspective. But I think what investors are most focused on is a very consequential slate of clinical catalysts readouts that are coming up in the fourth quarter and maybe potentially even beyond that in the broader pipeline.

And so we're going to try and drill into a lot of the key programs here. But before we do that, I just want to kind of give you the opportunity to make any high-level comments on what you've been spending your time on and what you're most excited about?

Thank you for the question. The -- there are 3, 4 things that I spend -- I joined BMS 10 months ago in most of the time. The first was, as you said, the short-term catalyst and be sure that we have been able to derisk all the studies, the big pivotal studies as much as we can. Because Phase III studies are set in times and during a conduction condition and change. And Phase III studies can fail for different reasons. -- operational reasons, study design reasons, patient populations and not necessarily you can change the science that is underneath a Phase III, but you can correct some of the risks that are intrinsic of every trial. So the first thing that we did that we are doing now as business as usual is identifying all the potential risk. Each trial can run into and everywhere can be different than the other and then try to mitigate them. And these are from an operational standpoint to statistical standpoint to -- so you can do that. So this gave me confidence that for the next wave catalyst, at least we did everything in our end to control the outcome. And then based on these learnings, make this as standard way of operating. And of course, you do this not also using technology because of the reasons. One thing we are doing is modeling outcomes using AI, using tools allocating studies originally 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 this 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 today tomorrow and the day after tomorrow. So you cannot simply have a short-term view, but you need to build your portfolio looking what the growth can be going forward. The last thing was more related on people and try, for instance, neuroscience is the best example because with the acquisition of Cobenfy we wanted to be back into this space. but we need to rebuild the unit, and this require also rebuild the people and bringing 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 these programs, starting with oncology at a high level. I mean, we just come off ASCO, very dynamic conference this year. Lots of focus again, specifically from a Bristol's perspective, or PD-L1/PD-1 or PD-L1 VEGF-bspecific class. So I guess I want to start with just hearing your updated thoughts on pumitamig in the context of the very encouraging data that was presented at ASCO and overall thoughts on the PD-1 PD-L1 VEGF class, particularly given the debates around Akeso, HARMONY-6 trial and the issues that were raised by the discussants of the stage when the data was presented, that fueled some investor debate. Are those really substantial concerns? Or is this a skeptics kind of potholes in the data?

I was a good ASCO. Thank you for bringing it up. It was my first ask on BMS, but was an exciting ASCO because I think as BMS, we were able to move from A lot of the presentation focused on Opdivo, 2 presentations showing the next portfolio. Pumitamig was one, we added Selmo. We can talk about that we have our ADC ISA brand. We have some data also we are PRMT5. So very exciting ASCO because we start to show that there is a portfolio and in oncology and solid tumor in hematology is start to be -- there is substrate. PDGF, important meeting for that class of agents. It may be 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 1 specific geographic region may have. Looking at our data, I am very pleased on what I have seen because we brought ASCO, the third global data set before we presented data in small cell lung cancer and triple-negative breast cancer. At this ASCO, we brought data in first-line non-small cell lung cancer in combination with chemotherapy. First of all, is more cell and triple negative, we vs consistency from China data and our global data. Here, we had the monotherapy data. This was chemocombo. But what I like our data set, first of all, clinically, in squamous cell -- so we have seen numerically higher response rate, what you would expect with a Parchem combo. What I've seen also was an outcome specifically exciting in not only in PD-L1 positive, but even more in PD-L1 negative with the response rate in the context of a small data set, but numerically much better than what you expected with pembro chemo that in PD-1 negative is not very much actually. And this was, in my view, corroborated by the preclinical work that we brought to the meeting. This is a BMS internal work showing why a bispecific delivering PD-L1 and VEGF inhibition can be better than giving the 2 antibodies as a combination. And this is because PD-L1 and VGFA is in the macro environment, to mobile environment. And when the drug are binding cluster is forming and the cluster, the drug and the 2 targets are internalized in the cancer cell. And this is happening independently of 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 a 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 this mechanism as a bispecific can be more selective and multimaterial PGF inhibition, help PD-L1 internalization and can help actually to increase the activity of Pier 1 because they can revigorate this response. So I believe that this mechanism, this bispecifics and our drug specifically can represent the way forward on improving other PD-1, PD-L1 inhibitors and can help us to go beyond that group of drugs and eventually expand because of AGF can open up other indication in colon cancer. The program we are doing this in collaboration with Biotech, the program is moving very, very nicely. We have a 7 Pater studies. We have a more than 20 combo study because the next step is not only delivering monotherapy or combo with standard of care is building the next level of regimens with a novel and the rest of our portfolio step in combo with the IDC, combo with other...

And I want to talk about that. But 1 thing just in the program itself, it seems to me that some of -- 1 of the themes coming out of ASCO as well as what we've heard from 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 III ready, which I think surprised some people. So what are the next milestones we should be looking for from pumitamig in terms of just monitoring the progress of your own program?

As I told you, we have 20 studies ongoing. Some of the pivot will take a little bit longer, but a lot of them are Phase Ib too, so we will continue to have a constant flow of data, both clinical, 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 across tumor types. And again, in a moment in which you will see some of the composite emerging. It means that probably the next steps as a pivotal study is going to happen.

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

First of all, I am a believer in ADCs because I am a believer in precision medicine. And I think in oncology, I'm a medical oncologist. In oncology, chemotherapy radiotherapy are working. The problem is that the lack of selectivity and specificity. ADCs and radio ligands are a better way to deliver these 2 modalities. So as a brand it is a very nicely engineered drug because first of all, it's a bispecific ADC, is an EGFR ADC. EGFR and F3 are 2 targets that touch most of the solid tumors and this drug is specifically a higher affinity for EGFR with a very stable linker and shorter life. And actually, what I like is that we don't have any rush. -- because the drug is very stable in the moment in which is injected is internalized and then metabolized. So we see consistent activity across tumor types. Our partner started the development in China, some ergo, more than 6,000 patients treated in China. So we have a very large data set for efficacy and safety in multiple Phase II. As you mentioned, there are 3 Phase III positive studies anymore on and in a different indication as fringe carcinoma, we presented resaw presented is esophageal cancer and triple-negative breast cancer, later line versus standard chemotherapy and China-only data set them a Phase III. And the activity is remarkable, especially because you get the PFS and OS in both trials with very important other ratios. In repenetrate breast cancer, the PFS ratio 0.9 from 3.5 months to 8 months and the OS, the other ratio is 0.6 from 12 months to almost 60 months median OS, in second third line triple-negative cancer, this drug is active. And the safety profile is very predictable. It's mainly mythological atonicity because it's a potent drug. It's a dart ADC. So I think -- but the discontinuation rate is very low. And in the global data set because now we have global ongoing studies, Phase II and we have 3 Phase III studies globally ongoing in EGFR lung cancer and 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 Pumitamig, for instance, or other player in our drug. So I'm excited about this one.

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

Talking about Iberdomide, -- let me start with the platform. I think BMS were able to leverage and to expand Celgene platform on protein-targeted degradation. I think this is a very powerful platform that is delivering important drugs that can degrade proteins like Akros Yolos in myeloma and lymphoma, but also other targets that are really key the cancer cells. BCL6 is an example that so far was undruggable and now we have a degrader in Reforma that can actually work very well in the space. The platform is delivering. We have 11 drugs in clinic, some like hyper messy, but also volcadomide in Phase II and Mattar at the beginning of the development. So I'm very excited about this because these are oral drugs, very combinable that we can put a standard of care across Onco. Iberdomide specifically, PDUFA date, as you say, August 17, and it would be, hopefully, the first drug approved as an NDA for MRD. But the data we presented at ASCO and said that we have to show how combinable is this drug and now can be integrated in the standard of care. This is both for ibetomide and aside our terms being oral drugs can be added on top of standard of care. And the scarier is on top of data and AndexXa. At ASCO, we show data in the context of a quadruple with that Bocad AndexXa 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 Vertex and then Iberdomide as maintenance, and we have seen a deepening of the response or the MRD response with iberdomide alone. So it speaks on the quality of these assets how potent they are or selected they are and how they can be integrated in the treatment that is becoming more and more fragmented of myeloma as add-on Iberdomide, next registration study will be in post transplant tesoreblimid as monotherapy.

And then maybe just quickly on Mezigdomide as well. Those Phase III data appeared encouraging in relapsed/refractory multiple myeloma. But interestingly, the data was presented on the back of J&J's Majestic 9 study, which was also impressive. So maybe taking a step back, we're hearing some conversations focused on choosing between CAR-T and bispecifics in the second line. So where do you see this Mezigdomide fitting into the multiple myeloma treatment 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 sermos will fundamentally replace Revlimid Pomalidomide. And this -- because they are better drugs, more selective engineer for that. And their combinability and they can be integrated in the current standard of care, but also the future standard of care. Actually, just last week, we published 2 papers in blood, showing how Mezigdomide can benefit T cells enhancing activity and their persistence. So I think this is just the beginning, and we have a great opportunity by integrating selmos in the treatment of myeloma.

Okay. And then Christian, maybe 1 last on oncology before we leave move on. Just to giving you a chance to comment on this. There was some impressive data yesterday on the PRMT5 combination with RAS inhibition. High level, what's your take on that? And how does that influence how you might think about the development of your own PRMT5 program.

There is another drug in our portfolio that I consider a very high priority because it's a good drug. The name is Navlemetostat and it's PRMT5 on Nenadeletion. Again, I like it because it's precision oncology. We presented the same data at ASCO that are more translational work, but also some updated on the monotherapy and lung and pancreatic cancer response rates are holding, 34% in lungs, 18% monotherapy. But the durability is very good, not only the response durability of stabilization. The drug is doing what it's supposed to do. Then what I really be like more is the combinability -- the safety profile on ablemetostat is very good. It's very mild. We have the 3 pillars. Convoking are Phase II/III in pancreatic cancer, Gem Abraxane. We know we can combine soon we're going to be in Phase III and in lung cancer with platinum doublet. This is the first entry. And then we are combined with pumitamig because it makes sense to combine with PDGF plus or minus chemo and the last is the combination with Elparas. The data you have seen yesterday -- very important also for me because derisking, the combo. And now we know that there is potential synergies of these 2 pathways. And actually, this is preliminary, very preliminary, but promising data showing that I'm very excited about the opportunity. And it's an exciting moment also for a very difficult disease like pancreatic cancer. I mean I'm so happy that these days, we're talking a lot about it because in many years that we didn't have anything.

Okay. Well, maybe we can pivot to cardio. And the NIVEXiAN-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.

Yes. The study was designed on the outcome of a very solid Phase II study, in which running total knee replacement is good surrogate for outcome. Testing a very wide range of doses, rings is a critical important aspect of the AIM study, because of course, was very important to find the right dose to ensure to have a similar efficacy because a year ago against it's not an add-on trial like an SSP, but is a strategy against apixaban. So you need to have a similar activity maintaining a profile on the bleeding side to ensure a benefit on that side. And I think the dose that selected 100-milligram twice a day give us that profile and the confidence that we can be a parity on efficacy. And then on the safety side, potentially have a benefit. The study is designed as a noninferiority for events, strokes and thromabolic events and then a superiority for bleeding, measure bleedings and no measure bleeding clinical relevant. I'm blinded, no news, good news, in my view. DMC continue to monitor the study in a regular way -- we have -- we keep scrutinizing the study conduction, how we are recruiting the events. These are coming as fun. 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, a predefined number of events for primary endpoint and noninferiority and also for the bleeding events both groups, and then we will see.

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

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

Yes. I think the conversations we would have naturally premarketing with payers. -- rests on that, where is that optimal mix -- because the message you'd like to leave with is we have superiority on bleeding. There is a cost to bleeding to the system for those patients who experience bleeding. And the question then, well, what is -- what's the trade-off? So hopefully, we do not have trade-offs and say we are not sacrificing any efficacy. So if you look at that alone and even to Christian's point, about 40% of patients on Eliquis, which is a big number, who are underdosed or not dosed and the cost associated with that in terms of foregoing efficacy or causing some unintended bleeds, there's a lot of value to the system there. So as we get the data, and we'll have a more fulsome conversation within the context of the Phase III data. But we would expect the value that, that potentially that brings to the system would be reflected in access pricing as we look to payers and to patients and prescribers. And I guess on that point, maybe just staying with that thread, Christian, back to you. How do you think about the commercial implications of hitting your non-inferiority margin, but with a point estimate of or a hazard ratio of maybe slightly above 1.

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

Yes. All right. Let's move to neuro. Let's talk about Cobenfy, maybe just open-ended question. Give us your latest framing and update ahead to be adept to 1, 2 and 4 trials.

Yes. The Cobenfy is a big area of focus that we're having. As I was telling, we are building to build a good infrastructure, a good unit in Europe. I'm very pleased that we are progressing, Consider the Cobenfy, we have 12, 13 pivotal studies ongoing. So it's a very large program. So there are 4 studies in psychosis, Alzheimer psychosis. There are 3 studies in bipolar, 2 studies in agitation, in cognition for Alzheimer and then Otis meritability. So it's a large program. We have multiple shots on goal. Psychosis is the first potential readout for the product. The base case is having at least 2 positive studies to be able to go and try to seek for an approval. As you know, ADAPT 2 and 4 are similar, even if there are differences because ADAPT 4 is a biomarker selective population. We wanted to have a more homogeneous patient population based on tau plasma assessment. Of course, this increased a little bit the -- more a little bit of the screening failures because we want patients that are positive, but it's progressing well. And ADEPT-2 now restarted. We learn from ADEPT-2 executional hiccups that we had and now I am full confidence how the program is delivered across. ADEPT 1 is a different study because it's a study in which we have not assessing like an adept 2 and 4 time-bound score that is measuring alienation and delusions baseline and after 14 weeks, but we are recruiting psychotic events. The patient start with Cobenfy and then is randomized to continue Cobenfy and placebo, and then the patient experiencing psychotic events is collected as an event. And then the analysis is based on a predefined number of events. So different studies, but they are complementary. So ADEPT 1, 2 and 4 are running in parallel. They should read out more or less at the same time, but it depends on the ends. So there is still we will inform why we will as we guided before.

And which 1 of those additional indications that you mentioned, does the ADEPT trials have the most read through to. The additional indications that you were talking about for the Cobenfy program.

I think psychosis is a very anchored on 3 factors: the first one, fundamentally showed good activity in the past for hallucination productive symptoms hallucinations and and delusions. We have seen schizophrenia in patient with these symptoms benefit. And when you have antipsychotic drugs that are working in 1 indication, you can translate that into other indications. This is why we believe that this can be beneficial also in psychotic events, in psychosis and alzhemier. And of course we have data from some of the open label part of the studies, where we see some activities, yet we did not disclose. So the 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 many in these patients that are experienced with bipolar underlying disease. So I think I believe that this is also an area where COI can bring benefit. Agitation, if you think, is very linked to productive symptoms. So in my view, is also an area that can be beneficial. Cognition is different. Cognition is different because while the prior trials are anchored more on N4 inhibition, cognition is more M1 muscarinic 1 receptor inhibition. So it's a little bit different concept. Overall, I believe that Cobenfy is a drug that in schizophrenia is bringing a lot of benefit to the patient. And it's a drug that will 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 Cobenfy because Cobenfy is an anchor, but there is substrate below Cobenfy. We are building a very strong Alzheimer's portfolio. We have an anti-tau antibody, and we have a famagal drug that can work both in MS spasticity and also in agitation that are in Phase II. Next year, we will have data with these drugs. And we will have some early development assets. So we are building a neuroscience presence.

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

Yes. Business continues to do well. The growth portfolio is delivering, executing on the pipeline. Obviously, as you mentioned and spoke with 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 is no hesitation on business development in terms of the question we get often, are you waiting to see all the Phase III readouts before you look to execute business development. There's no go slow order, so to speak. So we continue to look in the areas we know well where we understand the biology. We understand what the unmet need is. We understand could we get a fair return for investors. So we continue to look at that. And it doesn't need to only be acquisitions. We've got plenty of examples of partnerships, even out-licensing. So I think for us, focus on delivering on our numbers this year. The readouts will be what the readouts are going to be. We've done a very good job managing our cost structure as we go into the LOE period, we'll be a smaller company, and we want to have the appropriate cost structure. So when we turn that corner, we have got very good leverage from top line growth, again, durable, visible top line growth being translated into even stronger bottom line growth. So execution Focus are the clear mantras. And back to the end of the decade, our goal is to be one of the fastest-growing biopharma companies coming out of the decade.

Okay. That's great, Chuck. Christian, maybe back to you in the interest of time. We just have a couple of minutes left. I have 2 topics I did want to talk about. I'm going to let you choose. Aim parent and Camzyos, which ones where do you want to go?

Amiparent.

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

It's -- I like the target. LPA1 is novel. And pulmonary fibrosis is a disease. There are not so many options. having a drug that can bring a novel target is very helpful. It is a target that may work because we know LPA1 is attracting and inducing fibrotic process through fibroblast activity, but also induces cell death apoptosis for epithelial cells. So by blocking that target, potentially we can even increase the repair system. So I like this concept. Secondly, this is a drug that you can deliver as monotherapy on top of antifibrotic therapy because the profile -- the safety profile is very neat. The program has been -- the Phase II -- the Phase II, the Phase II was positive in IPF and PPF. The Phase III was very, very much run to try to replicate the conditions for the Phase II. This is the secret to have most of the time a good outcome in Phase III. In addition, I think we were able to integrate a higher dose that, in my view, helps because we have seen a dose relation in efficacy with between 30 and 60, 60 was actually the dose. But then we took the risk to put 120 into the Phase III. The DMC assessed 120 in a safety run-in and efficacy run-in and give the green line. Then the studies have been conducted, more than 1,200 patient studies, each one of them, 2 doses, 120, 60 placebo, -- and the good news is that we didn't have any safety signal in terms of hypotension, so episodes. So this is the a bit longer. And of course, we will see when we unblind the data, but we have 2 shots on goal and 120 can give us more confidence that we can have also a better outcome. We will see the results. Again, we don't have to wait too long because it's happening this year.

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

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

Christian and Chuck, thank you both very much. I know we went a little bit over, but there's obviously a lot to talk about. So I really appreciate your so.

Thank you.