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

Good afternoon, and welcome to the Barclays Global Healthcare Conference. My name is Carter Gould, senior biopharma analyst here at Barclays. Welcome. And next up is Bristol-Myers Squibb. We're really happy to have Bristol here, again, one of these companies that we've been looking forward to meet in person over the past 2 years. And joining from the company is the CMO and Head of Global Drug Development, Samit Hirawat. Samit, thank you very much for joining us today.

Thank you, Carter. Pleasure.

And in contrast to many of your peers, you have a very active 2022 from a catalyst perspective. A lot of clinical data, a number of launches coming up, so no shortage of stuff to talk about today. And in fact, you had a very busy week this week, having data both on Monday and Tuesday, ironically enough, in the same sort of therapeutic areas. So I thought that'd be a very logical place to start the conversation today. So why don't we start off with the LAG-3 data? We finally saw the full -- more mature data and some of the data points that we're missing. Can you maybe help put that full data set in context now that we have the overall response rates and your level of confidence around the upcoming PDUFA?

Absolutely. So thank you for the question, and thank you for having this meeting in person, first time for a long time, so that's great. Relatlimab plus nivolumab, it's certainly very exciting to see that the full data is maturing. Let's start off from where we were with the PFS, more than doubling of the progression-free survival. The data that we shared yesterday was 10% delta in terms of the overall response rate. If you think about overall survival, trending in the right direction, did not have statistical significance, but very important to note that we have a median now for the nivolumab arm, which is about 34 months. If you look at the confidence interval, the lower bound of this confidence interval is about 25 months. We don't have a median for overall survival for the combination arm, and the lower bound of this confidence interval is 34 months. And that becomes very important when we think about IOs in general and the shape of the curve and the separation that starts happening because the shape of the curve becomes very important. Overall takeaway for me, at least as I look at it, is we have a new therapy that is very effective, and the primary aim is to delay the progression as much as possible, and that's what nivo plus rela does, a trial that's compared the combination versus a very active control arm as well, you have to keep in mind. And that's what defines the hazard ratios and how you look at these data. So overall, pretty excited. Looking forward to the approval this week and ready for launch.

Okay. And I know there was some conversation last night when the data came out, just around some of the response rate, complete response rates against some of the historical benchmarks. You did compare against nivo in the study, which should address some of those questions. But any commentary on just the response rates against some of those historical benchmarks?

Yes. So historically, if you think about, again, within the clinical trial, we do have a numerically higher CR rate, numerically higher PR rate and overall response rate as well. So I think I -- personally, I don't like comparing across studies. The study was conducted in this era. So rather than going back 3 years and comparing for the data that was generated 3 years ago, where the treatment landscape was different, the way patients were treated were different, let's talk about what it is today because this is the area that we've conducted the trial. And similar to what we would do 3 years from now, if we have another study reading out, it would be better to compare the data then than going back 5 years and then starting [ doing that ].

Okay. Perfect. So we get that PDUFA to look forward to. In addition, we got the bempeg data on Monday. Clearly, a bit disappointing. And you obviously then also stopped the adjuvant study. The other studies in renal cell and in bladder continue on. Why shouldn't we read through those studies as this being a sort of a negative incremental data point that maybe portends poorly for those outcomes as well?

So 2 parts over here. First of all, truly disappointing with the outcome of the bempeg plus nivo trial, which compared versus again a very active control arm of development. And we did not see any addition of putting an IL-2 on top of nivolumab in the trial. And the data were pretty clear cut. You heard what our collaborators, Nektar, has said. And so therefore, the decision is made that there's no point continuing to follow up for overall survival. And then it extends into the adjuvant setting as well, and that's why that study was stopped, where we talked -- both parties stopped and we all agreed to it. As it relates to then trying to extrapolate this data and applying it to bladder cancer, renal cell carcinoma, I think it's a stretch, but those readouts are right around the corner within the first half of this year. And the studies are not like they're enrolling or anything. They've already finished enrollment. We've done the follow-ups, closed the database locks. So let's just wait for that rather than speculating on it. And the data will be what the data will be, and then we'll make the decisions based on the data. But truly, we are looking forward to the readout of the renal cell and the bladder cancer study.

Fair enough. So we've got a number of small -- it's good to see a company focused on small molecule drug development, and you've got a number of these readouts coming up, and you've got a PDUFA around the corner with mavacamten. Clearly, the centerpiece of the acquisition of MyoKardia not too long ago. When we think about sort of that PDUFA, are there any significant areas of uncertainty as we think about the label, I'll pick one, sort of monitoring? Are those areas of discussion? Or is it pretty clear and clean at this point as you think about the discussions?

So from our perspective, the data are very clean, very clear that there is a symptomatic and functional improvement for patients who have the disease or have obstructive hypertrophic cardiomyopathy that is very symptomatic. If we think about the overall profile that we've already seen from that study and the supportive studies and long-term follow-ups, the data are quite remarkable. We do believe they are transformative and they're distinctive. This is the first drug which will have the mechanism of action that truly targets the reason for the disease. And as we have spoken before, the delay in the approval was because REMS needed to be reviewed and it does take time. And in a division that does not necessarily have many REMS, it does take the time from the FDA perspective. So we are ready for the launch in April, and we are obviously not going to get into the specifics of that yet. But certainly, remember what is the mechanism of action of the drug. It relaxes the heart a little bit. And so you don't want to have too much relaxation. Otherwise, the ejection fraction can be impacted. So those are the elements that we have to just keep in mind. But it is a drug that has major implications when we think about what the outcomes could be for patients with obstructive hypertrophic cardiomyopathy.

Right. And then you have some additional data coming on mavacamten at ACC, the VALOR data and somewhat of a more severe population that's looking at potentially other options. Can you help maybe put that data in some context? Should we think about that as just potentially being label expanding or maybe having more of a commercial impact or serving some other purposes, maybe just help level set expectations?

So I think, Carter, let's put regulatory and commercial because they are further away. But what's the clinical implication of that? That's I think the most important one. You already said, this is a more severe population. Patients were already on calcium channel blockers and/or beta blockers, and about 20% of patients are also at disopyramide. So now, we are looking at patient population that is now looking forward to having an open heart surgery and septal reduction therapy. But instead of going there, we randomize the patient to receive pharmacological intervention with mavacamten and see at 16 weeks, are these patients still willing to, or are still eligible to undergo septal reduction therapy? And the data will be presented in a couple of weeks, and you'll see what the outcomes are. We are pretty excited when we look at that data. If you think about what is the surgery and what is the implication of that, number one, it does have comorbidities associated with surgery. You have to go in the hospital, get surgery and all, it's open heart. Second, in the best centers that perform these set of surgeries on a more regular basis, the mortality rate is about 2.8%. In the next level of centers, which do perform but not as regularly, the mortality rate is about 5.6%. And if you think about centers that perform them rarely, the mortality rate really hikes up to 16%. So this is not something that is willy nilly. And if we can really bring a therapy that has the same outcomes that we are looking forward to in terms of patients with obstructive hypertrophic cardiomyopathy, then pharmacological intervention will always be better from my perspective as opposed to surgical interventions. And let's see what the data will be at ACC, and then we can get into a deeper detail of what we saw there.

Right. And then when we think about sort of label expansion, whether it's non-obstructive or in the HFpEF, how are you thinking about that at this point? Maybe just give us a state on those efforts?

Sure. And so based on the MAVERICK data that we saw and the longer-term extension and the impact that we saw on the biomarkers and other parameters, we are looking forward to initiating a Phase III trial in nonobstructive hypertrophic cardiomyopathy. And then the HFpEF study is already ongoing. It's a small study but a proof of concept study, which will be very important as we look to the future implications and development path.

Okay. And only because I had them in the room an hour ago, and we teed it up. Just how you think about sort of competitive differentiation. Clearly, there's a company couple of years behind you, and just how you think about differentiation, if at all, and competitive dynamics...

To me, the differentiation is actually what is the amount of data that we are looking at. So again, not doing cross-trial comparisons because I don't know that drug as well. But if you look at the data that has been available and what we have, we've got Phase III trial already completed. Looking forward to a launch in 1.5 months or so, at 28 April, right? We've done another Phase III study, VALOR, showing the results that you will see in a couple of weeks. We've got data in nonobstructive hypertrophic cardiomyopathy. So I think when we look at that data set and the data set that we've seen from the competitor molecule, number one, largeness of the data will trump it. Number two, we haven't seen any differentiation, truly speaking. The way the patients were enrolled, the types of patients enrolled, the way the primary endpoints were measured in terms of Valsalva maneuver versus exercise-induced, change in the gradient, et cetera, we don't see the differentiation standing out. So I think having a first-mover advantage, having the data set that we have truly differentiates us in a better way, if at all.

So I'm going to ask one question, pushing back on that, and then we'll move on. And that is how do you -- I guess, how would you answer the pushback to that on sort of they potentially having faster titration and how that might matter clinically?

So let's see when the data reads out of the Phase III study because remember, the mechanism of action remains the same. And the REMS is dependent on that. So you have to wait for that data to read out from the trial and how the trial is conducted and what that actually leads to in terms of clinical outcome.

Okay. Perfect. So let's move to deucravacitinib.

My favorite molecule.

Mine, too, within Bristol. I think -- it may be your favorite molecule, I'm pretty sure this is not your favorite question, though, in terms of how to -- how we should be thinking about the label and expectations there, to the extent you can say anything. But clearly, there are a number of points of focus that -- really, one overarching.

So the reason it's my favorite molecule, and this is my favorite question, is because we have rehearsed this answer so many times, answering it again and again. And the true nature of it is, if you think about it from a clinical data perspective, we've seen the data in POETYK 1. We've seen the data in POETYK 2. We've seen the psoriasis data from the trial in China. We've seen the data from the trial in Japan. We've seen the data from psoriatic arthritis Phase II studies. We've now seen the data from the SLE trial as well. And these are all positive proof of concepts as well as registration-directed trials in psoriasis. We have not seen the profile emerging that says that this is a JAK inhibitor. That's the implication of your question, right? And so from a lab parameters perspective, we don't see those dramatic changes in liver function tests or in the bone marrow function. So we truly do believe that the efficacy profile differentiates itself compared to Otezla, which is the current used medicine for patients with psoriasis, which is moderate to severe. And from a safety perspective, it differentiates itself quite well from a JAK inhibitor. Now we're not going to get to the specifics of what is happening with the regulators and a quick Q&A. But certainly, we believe that the data stand on themselves, and you'll see what the label will be, and we're looking forward to a launch in September. And then we are looking forward to initiation of the SLE Phase III trials towards the end of this year or early next year as well.

My opportunity to editorialize here. I understand fully the debate between clash labeling, not clash labeling. I think either way, they're going to sell. The issue of whether they sell a lot in psoriasis or a hell of a lot in psoriasis, and I think the drug is pretty well positioned there. One question, though, is on the [ UC ] data. Clearly, that was a negative outcome. But even -- there are different pieces you can -- placebo arm certainly outperformed. But I think when you think about that dose that you guys took forward there and sort of the rate of acne and rash and what that maybe portends for some of the other indications where you're looking at higher dose, how do you get comfortable with the dose above and beyond kind of what you explored in psoriasis?

So again, in any given clinical trial and any given asset level program, one has to look at the totality of the data from across the programs. And if we combine all of the data sets from the appropriate doses and pull the data, you don't see that dramatic increase in the rates of Grade 3, 4 or Grade 2, 3, 4 acne and the rash. So overall, we are comfortable, but the trial will have to stand on its own. When the data reads out with a larger number of patients enroll at the higher doses, then we'll be able to look into it and say if it's treatment-related, disease-related or something else. So I think we just have to wait for that. This is a hypothesis-generating trial. It was an interesting thing that you bring up from the safety perspective, but I also look at it from an efficacy perspective. There's a small subset of about 30% of the patients who were treated with a prior biologics. And here, there is a 0% response rate in the placebo and 26% on deucrava. So these are all hypothesis-generating data sets that we'll need to read out when the trials read out.

We struggled mechanistically to figure out what we do.

We do, too, because we don't know how that will pan out when we look at additional data sets that we will read out, and then we'll have to make decisions on where ultimately it will take.

And maybe we just take a step back and think a little bit more theoretically around I&I and particularly since you guys have such a role in orals now. Just when you think about combinations here with such promise and hope that that's eventually the path some of these indications might go down, are there any sort of fundamental kind of pillars that you build off of to think it will help guide you in that process and where you anchor and then build off?

So obviously, this is a number of indications as a single agent that we are currently developing. We'll continue to look for opportunities where the combination should play a role and how they should be combined with other modalities within which disease. And it will be dependent on that evolution of the preclinical data and maybe some clinical data from very small studies that might be conducted. But today, we are not ready to talk about a development plan from a combination perspective.

Okay. Maybe move on to Milvexian, which obviously had really outstanding data late last year, and we're waiting for some additional data coming on the horizon. I know you've talked about sort of that data helping judge or helping guide you in terms of picking indications. But are there other key aspects beyond sort of that efficacy data and the bleed rate data that will help guide that decision? And is it -- are there other kind of nuances around the profile that will help kind of shape that decision?

It is a pertinent question, truly speaking, because if you think about the TKR data, we saw the dose response relationship from an efficacy perspective. There was flatness in terms of risk. So increased doses did not lead to increase bleeding. That's great, but it was only for up to 14 days. So the SSP study for which we'll have the data in-house by around the middle of the year, we're looking now 90 days' worth of dosing on top of double anti-plated agents, 21 days of clopidogrel and then continuation of aspirin up to 3 months. So we look at overall data set and then say, okay, where are anti-plated agents right now used, and those are on the arterial side of the disease. Where is Factor XIa used on the venous side of disease. But now if you've got an anticoagulant and you've got anti-plated agents and you have the combined ability, now you open up plethora of indications that you could pursue. So it will depend on the profile that emerges from a benefit perspective as well as the risk perspective. It is not just about the bleed rates but all over the BTEs and other embolic or thromboembolic episodes that might occur. And all of that data will define the benefit risk and give us a better chance of defining what is the dose that we need to take forward along with our partners in Janssen.

So one of the other -- ACC is also going to be, I guess, notable because we're going to see some competitor data in this oral Factor XIa space. And obviously, there are other approaches, potentially more long-acting approaches. When you think about sort of the competition in the space, are there any kind of key aspects where you think you -- that you would kind of call out for folks as they think about competitive environment, which is clearly sort of heating up a bit, and I'm will only intensify going forward?

Yes. therapeutic gives us an area such that we have competition everywhere, but it's the promise of the scientists who develop the drugs and the drug developers who are designing the studies that will ultimately pave the way. And the one proud thing about BMS, I have to say that the 3 drugs that we're looking to launch this year are all first in class, and it doesn't happen by luck. It is a thought process and a development process. So from an ACC perspective, as we look forward, certainly, we'll learn from the data that everybody else has presented. But one thing is interesting to note that do you really want a long-acting anticoagulant if there is any bleed risk? So having a short-acting might actually be better from that perspective. And then you certainly do have the daily dosing associated with that. But if there is any trouble that occurs, you can pull it back and you can control that and -- from a risk management perspective, but looking forward to what the competition is going to present and then what we can learn from there and take it into our program as well.

And I know you don't give specifics around the clinical development path thereafter. But I guess when we look at Eliquis, there was sort of a -- maybe not sequential, but a little bit more of a staggered development path when we thought about some of those follow-on indications. Generally speaking, should investors think more sort of following that path, at least kind of in concept? Or is this potentially going to be more of a go big right out of the gate in a number of indications?

Yes. And maybe this is a question for second half of this year once we have the data because, again, we know what we're talking about, but we haven't really honed in into the right place yet for the indications.

Okay. And then when we think about sort of Eliquis' role going forward, how should investors sort of think about that? Clearly, there was an LOE, albeit further on the horizon than maybe someone had thought a year or 2 ago.

So in general, cardiovascular studies do take a lot of patients to be enrolled, the timing of readout and how the data will evolve. So Eliquis will continue to play a role. It's a very important drug for patients who really need it for AF and [indiscernible]. So that will continue on. And then when the data read out, then you can have a discussion on how is the placement is going to go. It is all data-dependent and what the trial designs are going to look like. Do we compare versus that? Do we compare against something else? And so the places will depend on those readouts and the data sets that we would have at that time.

Okay. Maybe moving to multiple myeloma, and I know a space near and dear to your heart. When we think about some of those sort of emerging modalities, and obviously, Abecma got approved, you have this sort of challenge of having all these agents and trying to find a home for all of them or at least communicating to The Street kind of where they might be positioned. How do you kind of work through that challenge, and think about the coexisting of a number of these agents? Clearly, some of them are orals and antibody conjugates and cell therapies and some may be more prone to certain populations than others. But from a high level, maybe help think about positioning there.

So I think there are 2 important facts of multiple myeloma: one, the disease is not cured; and two, there are multiple modalities that are approved and very efficacious that are applied in a sequential manner to treat the disease. So if you think about cell therapies, most effective right now, right, but in the late stage of the disease. Now the profile of each of the cell therapies will define how they move further up. So if you have safety elements that are going to be challenging, and you might have read the guidance that came out yesterday, or you will read the guidance that came out yesterday from the FDA perspective, they already start talking about you need to really think what patient population you're going to enroll in your clinical trials, how are you going to manage the safety, are they going to be life threatening, and they clearly call out toxicities and cytokine release syndrome. They are going to be very, very critical to continue to monitor and manage. So I do believe that small molecules and combination of small molecules will continue to play a very big role in the early settings of this disease, whether it be newly diagnosed or in the post-transplant space, or up to 1 to 2 prior lines of clinical -- of treatments. And that's exactly where we are beginning our development program from a cell mod perspective. This year, we are initiating the Phase III trial of iberdomide in combination with daratumumab and dexamethasone comparing versus VELCADE, daratumumab, dexamethasone. Early next year, we'll be initiating trials with 480 comparing versus pomalidomide as well as combining with Kyprolis. On the other end, for Abecma, that program is evolving as well. We're looking forward to the proof-of-concept part of post-transplant space use of Abecma, of how that evolves and we move the profile that we have to that set of patients who might need it as a maintenance or post-transplant maintenance setting. And then, of course, we have the [ CARDINAL III ] trial that we'll be reading out next year. That will certainly pull it into a slightly earlier line compared to where it is today. And then in the earlier development program, we have the T cell engager, we've got ADC and the next generation of CAR T cell therapies of GPRC5D as a target and then the combination of BCMA GPRC5D. So from a BMS perspective, we've taken a holistic approach because we do believe that, ultimately, patients will continue to need staggered approaches in terms of how sequentially they should be treated. Can we ultimately get to a place where we are curing some of the patients? That remains to be seen. But each one of them will have to play a role in a differentiated manner because just like mutation-directed therapies have played a role in solid tumors and patients are segmented out now, in myeloma, there will be segmentation at some point based on these therapies and modalities.

Okay. And maybe just in the final seconds while we're wrapping up, when you think about the challenge of justifying iberdomide against a world in which we're going to have generic Pomalyst and generic Revlimid, just again maybe underscore the efforts the company is taking to really kind of drive home that value proposition.

So again, the development program, that's why it starts off where the most applicability will be, go further up and further up. So for 480, we're looking to compare versus pomalidomide, which, as I said, starts next year. For iberdomide, we are placing it against Revlimid. So the initial trial is not doing that, but a follow-on trial in the earlier settings will be comparing that versus Revlimid.

Perfect. Samit, thank you very much for joining us. We'll have to wrap it up there, and looking forward to the rest of the year for you guys.

Thank you, Carter. It's a pleasure.

Thank you.