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

Good morning, and welcome to the Bristol-Myers Squibb session within the Cowen 41st Annual Healthcare Conference. We're delighted have Bristol with us again this year. Representing the company is Samit Hirawat, who's Executive Vice President and Chief Medical Officer. There's so many new developments and new products and new initiatives at Bristol that it's a full-time job to keep track of them all. But the best person on the planet to give us an update on all of them is Samit. So Samit, thank you so much for spending this time with us.

Thank you, Steve.

I'd like to start out by asking, Bristol has numerous -- has had numerous positive clinical trial readouts over the past year. What are the next clinical catalysts that you're looking forward to seeing over the next couple of years?

Thanks, Stephen. It's certainly a pleasure to be here with you. And over the years, I've had the pleasure of discussing many R&D-related topics with you and certainly very informative. From a Bristol perspective, you're absolutely right that 2020 was a year of a lot of positivity coming out of the pipeline. Looking at 2021 and a couple of years beyond that, as we've shared earlier in the year during our earnings call as well, the inflection points that are coming up. So if we take 3 categories of bringing in new medicines or new molecular entities, we had the approval of liso-cel already this year. We are looking forward to the approval in the near term for ide-cel. We've already filed in terms of the extension or new indications. We've already filed Zeposia for ulcerative colitis, and we'll see the approval, hopefully, at the end of May. We've already shown the positive top line -- that we will be showing the positive top line for deucravacitinib later this year. So that is going to be into filing and hopefully, available to patients next year for psoriasis. But in addition to that, I think the next approvals coming for Opdivo from the adjuvant indications perspective, life cycle management of that product for additional readouts over the years. And then, of course, from the Factor XIa perspective, looking forward to the first readout of the first Phase II study in total knee replacement that will drive the future development process as well. So these are just a few of the infection points in 2021 and early 2022, but certainly, a very healthy pipeline and looking forward to developing it and looking forward to more positives for the larger patient population with serious diseases.

Great. Let's spend a moment on deucravacitinib. So when we get the full Phase III data, as you mentioned, later this year, what would you suggest that investors focus on? In Phase II, deucravacitinib was about twice as effective in achieving PASI 75 as was Otezla. Should that be the bar in Phase III? Or sometimes Phase III trials aren't quite as good. How would you ask us to approach this data?

Sure. And thanks for reminding everyone that there are 2 Phase III studies that have recently read out. And we recently got confirmation, so this is sort of breaking news in a way. We will have the ability to present both of these Phase III studies at AAD in April. So you will be able to see the full data set. And certainly, that will pave the way for our discussions with the health authorities as we continue to get engaged in that side. We will not get into the specificity of data now. We are only 6 to 8 weeks away, so you will get to see that yourself. We do believe from our perspective, deucravacitinib will probably be the oral agent of choice because of the profile that we continue to see and as it is evolving with the data that we have. And the reason I say that is if we look at it from an efficacy perspective, not only is there the statistical significance that we require -- that is required for the filings, et cetera, but it is clinically meaningful improvement versus the currently used oral medication, which is Otezla. And because of its mechanism of action to specificity in terms of inhibition of IL-12 and 23, I think the safety profile will also define itself. So something to look at, to pay attention to, both from an efficacy perspective and safety perspective. And because of that specificity and where it is hitting in terms of pathways, it opens up the space for looking at future indications as a broader medicine for autoimmune diseases of multiple indications, such as IBD, SLE, et cetera, that will start to show data later in the year.

Why don't we spend a moment on some of those potential new indications. I think there were 5 or 6 that were mentioned at the R&D event you hosted in June. Can you kind of just maybe rank them, the top 2 or 3, in terms of their potential and ability to really influence the trajectory on the -- of the molecule. What are the ones that you think could really be meaningful commercially?

Absolutely. Being an R&D person, let me say that, first of all, from a mechanistic perspective, it is a differentiated medicine that will have applicability probably to a larger extent in multiple autoimmune diseases. So first of all, psoriasis we just talked about, but then we also have shared the data in psoriatic arthritis in the Phase II study. We are imminently starting the Phase III program in the psoriatic arthritis space, as you will see coming through. You know that we have studies that are already ongoing in ulcerative colitis. And the Phase II study will have a readout at the end of this year, and that will pave the way for future development options for that disease. We will have the Phase II readout for systemic lupus erythematosus as well at the end of the year or very early next year. So looking forward to that, which will also then lead us into that indication. Study also ongoing in Crohn's disease, and that data evolves in 2022. And so that will lead us to that indication in the future if data is supportive. And then there are multiple other indications that will continue to emerge, and we'll pay attention to them as we build towards a larger program for deucravacitinib in the future.

Okay. I should have mentioned at the outset, if any investor on the line has a question, you can either e-mail me or Mike. Or you can submit it online, and we will read your question to Samit. Maybe we can move on and let me preface this by saying Sanofi was at our conference yesterday. And as you can imagine, they were citing some of the potential risks with agents, which work through the pathway that deucravacitinib works through. And they were basically arguing that there's a common pathway in all agents where they're, regardless of their configuration within the JAK family, are funneled through the same pathway and, therefore, there's this potential risk. Why is that not correct, Samit?

So I think scientifically speaking, and we've done multiple experiments, and we should certainly start to understand that not all pathways work in the same way and not all molecules are JAK inhibitors. Certainly, we know what the concerns are around the JAK inhibitors. When we think about deucravacitinib, and the reason we continue to say that it's a TYK2 inhibitor is because we've done the medicinal chemistry. Our scientists have really designed the molecule for that specificity to work through that pseudokinase domain of TYK2 to have a very specific downstream effect on IL-12 inhibition, IL-23 inhibition and interferon alpha inhibition. And what that leads us is into that profile from both efficacy perspective, which, as you will see the data, will continue to show how it lines up with those inhibitors of IL-12, IL-23. And from a safety perspective, that we are not seeing those signals of latter abnormalities. We are not seeing signals of those cardiovascular events or VTEs that would be of concern. So we do believe, from a preclinical perspective, from a clinical data perspective, which is confirming our hypothesis, we feel very comfortable as we look forward to presenting these data and taking them to the health authorities. Now of course, what the health authorities will decide based on the data, we'll conform to that. But we do believe that the differentiation that we have brought together in the design of the molecule, and the conduct with trials and the data that we've been able to generate differentiates itself.

Okay. Great. One more question on this topic and then we'll move on to other topics. So Bristol has a follow-on TYK2 in development. How is it differentiated from deucravacitinib?

So at the current time, it's in a very early Phase I, early Phase II study. And primarily, the way I think about it is that you always want to have a backup plan just in case the first one doesn't pan out. But I wouldn't really raise any alarm signals that, one, that we are going to accelerate that for some reason. It has to show its own activity. It has to show differentiated profile versus deucravacitinib now that we have the Phase III results already in hand. But nothing that we have today that we can talk about in terms of differentiation of that molecule.

Okay. Let's move to cardiology, and then we'll move on to oncology, where my colleague, Mike, also has some questions. On cardiology, so we're all very excited about your Factor XIa. Is the Phase II total hip -- total knee replacement trial on track for readout in the second half of the year? I know you had indicated, and it's very understandable, that COVID might have an impact on that. So what is the latest update on that trial?

Sure. So we are still very confident that we'll have the readout of the total knee replacement study in the middle of this year, in the second half of this year. And then for the secondary stroke prevention study -- which is very important, I think, for overall definition of the molecule from both safety perspective, dose defining perspective, and early indications of safety. Because the secondary stroke prevention study really is looking at the background therapy of anti-platelet agents and how a Factor XIa inhibitor can be safely combined. And that study should readout in the early part of 2022. The proximity of the 2 readouts does allow us the ability to not only build a clinical development plan and be putting it front and center in terms of our excellence and execution of the Phase IIIs when we are ready to do them. But looking forward to those 2 readouts and then defining the overall profile for the product and then taking it forward.

Okay. When you were answering about the total knee replacement, you mentioned midyear, and then you also said H2. So can we assume it's going to be early in H2?

Seemingly that way. That's how I would look at it, but we don't have the exact date yet.

Okay. And so this is another pathway, which, with other molecules in past years, issues have arisen. So how often are safety checks? And are you comfortable with the safety profile so far?

Look, there is a data safety monitoring board that is overseeing the Phase III -- or Phase II development program. These are randomized trials, very large randomized trials. So there are periodic safety checks through the DSMB, and no alarms have been raised as far in terms of us having to intervene at any point. So we are comfortable with the emergence of the data. We obviously don't have the unblinded look at the data yet. So keeping it closer from that perspective.

Okay. And is a head-to-head with Eliquis in the plan somewhere down the road? Or is that not a trial that would need to be done?

No, I think it will depend on what the indications that we're going to pursue and what the indications that require Eliquis as a control arm. Those are elements that are going to have to be discussed, not only within the company, within the sponsors of the study but also with our partners as well as with the regulatory agencies that -- what would be required if we were to pursue indications that currently are in the label for Eliquis as well. So too early to comment on that, but certainly something that we'll have to continue to debate.

Okay. And here as well, you have a backup. Is it similar to the TYK area where you just want to have a backup just in case? Or is there anything differentiated about BMS-209 (sic) [ BMS-986209 ]?

No, I think the same principles that apply, that you always want to have the backup plan. Because if you believe in the science, if you believe in the target, if you believe that, that mechanism is important and you're going to take it forward, then you want to have a couple of opportunities in your hand so that you pick the best one to take forward. And we have no alarms that have been raised for the current incumbent and the front runner. So again, working at the regular pace for the backup molecule.

Okay. Let me ask -- moving to oncology. Let me ask one question, then I'll send it to Mike. So the first-line renal space is ever evolving, rapidly changing and large opportunity. So given the recent data, how do you size up the efficacy and safety profiles of the various regimens, including those that Bristol has?

Sure, Steve. Look, I think from a patient perspective and how physicians are treating patients with renal cell cancer in the first line. There are 3 major elements: One is, of course, I-O/I-O combination. Second is I-O/TKI combination and third is single agent TKI. When we look at what Opdivo and Opdivo, Yervoy have brought to the forefront, we had the first study that read out for Opdivo, Yervoy, and we saw the overall outcome, which now is now 4 years of follow-up that shows us that we still don't have a median for the duration of response. And so for those patients with intermediate and high-risk renal cell cancer, I think it is important, that it's a very, very critical element for the treatment option that physicians have for those patients. With 9ER, what we have seen is the expansion of that in terms of having the low-risk patients also included now. So you have the ability to treat or use I-O with a TKI for treatment of patients with renal cell cancer. I'm sure what you're alluding to now is the new emergence of the data from the CLEAR study. Of course, we've seen that. And it's important to realize that you can't just put all eggs in one basket and say they are all the same. Because you have to start to see what the differentiation might be in terms of patient populations that have been enrolled in those studies versus the 9ER study. What's the emergence of the safety profile? And very importantly, what is the follow-up time? And so having that 4-year follow-up for I-O/I-O, having more number of the intermediate, high-risk and not just the low-risk patients included in the 9ER study, and having a safety profile that is well understood for 9ER at this time and having probably one of the best TKI combinations, I think that's put us in a place where we know it is a competitive space, but we are used to it in the renal cell space right from the beginning of the days. So we feel very confident that our profile will certainly pass muster, and physicians and patients will have the opportunity to use it to the extended that they should.

Mike, I'll turn it to you.

Great. Samit, I was wondering if you could talk a little bit about the CELMoDs in your portfolio. Maybe there are several. Maybe you could give us a lay of the landscape. So how are they similar or different from marketed agents? How are they similar or different from each other? And how well-characterized are their targets? How are you positioning the indication?

Sure. And thank you, because it's a large question and not just specific to multiple myeloma. So I'm glad about that. So CELMoDs, certainly, from a platform perspective, a very promising way of looking at targeting and building drugs for targets that were considered to be non -- are undruggables, right? So from a CELMoDs perspective, which leads us into the protein homeostasis and protein degradation aspect of the platform. And it becomes very important, and we've begun to see the emergence of the data. When we think about Ikaros and Aiolos degraders, such as the first CELMoDs in multiple myeloma, CC-220 and CC-480, that is telling us that our hypothesis is sitting well. We've seen the response rates 2 years ago for CC-220 with 30-plus percent response rate. And with 480, we've started to see the 50-plus percent response rate, as was presented recently last year, actually 2020. From the multiple myeloma perspective, the way we look at the 2 agents are -- there is a higher potency for one and, therefore, we do see a profile that has a little bit more neutropenia for 480 as opposed to iberdomide or 220. And we have the larger expansion arms now ongoing for both studies. First of them, the 220 study will read out this year. 480 will read out next year. And depending on the magnitude of response, duration of response, we will be able to then have conversations with regulatory authorities in multiple myeloma. But beyond that, we have several other agents in development. There is the 282 asset, CC-282 (sic) [ CC-99282 ] in lymphoma, that is being pursued as well in addition to the others that I talked about. We have new agents that are being also looked at in the leukemia space. So I think we are just at the beginning end of the CELMoDs and beginning of discovery of these new molecules that are going to be protein degraders and really a very promising area where we will be able to go through our library that we've been able to now build and bring new molecules for a multitude of diseases. And just as an extension of that protein degradation platform, we're also looking at ligand-dependent degraders of targets. So such as the first one, which is in the clinic, is the androgen receptor degrader, and that is in the prostate cancer setting in the Phase I trial. So once that data evolves, we'll learn more.

Great. So you touched on this a moment ago, but could you give us a little more detail around filing time lines for iberdomide? You mentioned bringing out the phase -- early phase data in multiple myeloma at the end of the year. Is that sort of on an accelerated approval pathway in your mind? Or how do you -- how should we think about filing the time line?

Yes. So as I said earlier, for both of the studies, so CC-220 or iberdomide, we're looking at the readout of that fourth line plus population data within this year. And so depending, again, as I said, depends on the magnitude of the results and the durability of those responses that we will hopefully see, will dictate as to how to approach and when to approach the regulatory authorities and what type of approval. For 480, we are in -- we have just begun the expansion phase, so that readout will be next year. And depending again on the similar attributes of response and durability and the patient population that will be enrolled into the study will dictate as to the approach and how we go. Very importantly, though, if we think about the overall multiple myeloma strategy, we have to not only think about CELMoDs, but the combination of those CELMoDs with standard of care and future therapies. And so this year, we're also launching the Phase III program in the earliest setting for iberdomide that you will start to see, and that will pave the way for bringing these CELMoDs to an earlier line of treatment. Because the ultimate aim is to be able to compete versus IMiDs and at some point, replace them.

You mentioned this is why you touched upon the androgen receptor degrader. Clearly, the chemistry associated with CELMoDs would sort of lend itself to some opportunistic avenues that you could go down in terms of looking at other cancers, but also potentially other therapeutic areas. Is that an approach that Bristol is taking? Are you sort of screening your library periodically for targets that might be interesting in, say, immunology or neuroscience or other areas?

Yes, Michael. So as I said earlier, our understanding of protein degradation continues to evolve and increase. So we do have several targets that have been identified, but we have not spoken about them publicly. So I won't go deeper into that. But yes, across the areas of our interest, we have several targets that we are continuing to build our molecules for, ready for taking into the clinic. As I said earlier, we've already gotten to lymphoma. We've gotten into multiple myeloma, solid tumors, and we'll continue to evolve. A very exciting field, and I truly feel fortunate to be working in that field at this time.

Great. I'll turn it back to Steve.

Let's talk about some other exciting targets within your pipeline. Let's talk about maybe relatin...

Relatlimab.

Yes. And so we're heading into an upcoming pivotal melanoma readout. Maybe you can kind of frame what our expectations should be for this readout?

Sure, Steve. If you recall, for LAG-3, this trial started as a Phase II/III study. So there was an interim look by the DMC to make sure that this trial can proceed from a Phase II and convert into a Phase III based on statistical principles. So obviously, we crossed the significant boundaries, and that's why it transitioned into Phase III, which is going to readout imminently. So the specificity of the data will be available once we have the readout. The idea around here is to be able to show superiority of the combination of relatlimab plus Opdivo versus an active competitor of Opdivo itself. So that superiority is going to be important. But more importantly, I think out of this trial, what we will see is also the emergence and outcome of the biomarker data, which will tell us how to proceed further. What are the signals that we need to continue to chase and pursue for potentially additional indications or additional combinations thereof? Because I do believe -- I think our philosophy will continue to evolve around newer I-O agents. Are the newer checkpoint inhibitors and newer I-O therapies going to be applicable to all patients? Are we going to start to see a convergence into a precision medicine-like mode where we have to preselect patients? So I think that's what I'm looking for from the relatlimab data. Will it start to give us that signal of where we should really go and the specificity of that going forward.

Okay. Even more readouts are coming in the second half. Bempeg, for instance, I think there are 5 pivotal trials that will be reading out in the second half of this year. What is your level of -- or how has your level of confidence changed on this in the last 6 months, maybe based on an interim look or other data? I mean how are you feeling about these readouts?

Steve, we've always spoken about that we will continue to follow the data and the science that emerges. And therefore, our limitation in terms of how we want to evaluate the 5 tumor or 5 trials, the 3 indications in renal cell, of course, the melanoma and the bladder studies. Just a minute correction that the first readout is anticipated in 2022, not in 2021. Some of that is COVID-related and on -- so on and so forth in terms of the overall impact on the studies. Having said that, our intent is to certainly look at continuing to evolve from a superiority perspective, trying to demonstrate, just starting with melanoma, but then also in renal cell as well as in bladder, how that IL-2 combination or per duration will evolve in terms of improving the outcomes for these patients. We obviously don't talk about interims and all that because that's not the intent here. But certainly, we were more comfortable with the data in these diseases when they were available from the early studies, and that's why we have pursued these and not other indications.

Okay. Let's spend a moment on TIGIT. So Bristol has a TIGIT, but it is not -- has not been advanced in pivotal trials that we know of. I think that in June, management said that you were determining whether the profile was unique or optimal in any way. Where does that process of evaluating this molecule stand?

Yes. Our TIGIT inhibitor is in Phase I study, defining dose and the safety and the profile of the medicine to see if there are signals of activity that we can start to see. We are not yet ready to get into a later-phase study or looking at combination data yet. We are obviously aware and have had discussions around where others are going, like Roche or Merck and others. Because those studies, they were randomized studies, they generated the data. As I said earlier, one has to keep on looking as to what are the elements that are going to be important in a TIGIT inhibitor. And then what populations are the ones that are showing the benefit of the combination of a TIGIT with a PD-1 inhibitor. I think thus far, and I'm guessing you would agree that the higher impact has been seen in those high PD-1-expressing populations in non-small cell lung cancer. So it's certainly an indication that others are following. We are behind in this one, and we have to now see where the data takes us as it evolves from our Phase I study. We are not there yet.

Okay. A couple of other topics in our last few minutes. NASH, so Bristol has a footprint in NASH. It doesn't get a lot of attention. FGF21, for instance, is a molecule in your pipeline. So what should we be thinking about Bristol's future in NASH?

So overall, fibrosis portfolio certainly is part of our pipeline. We have the FGF21 in NASH: 2 studies, FALCON 1 and FALCON 2, in F3 and F4 populations that are right now being conducted. We will see the data later this year. And that will define the path forward in terms of how the data evolves and how do we then follow the science, should we be thinking of combinations, et cetera. But since these studies are, again, blinded studies, we don't know ultimately what the data will tell us. And once that is available, we'll certainly talk more about it. But certainly, our overall fibrosis pipeline is composed not only of the NASH component but also the pulmonary fibrosis component with JNK-1 inhibitor as well as Lp(a) one. So pretty healthy from that perspective, but data will dictate ultimately where we end up and where we go and chase it.

Okay. Another product, branebrutinib. So Bristol has chosen immunology indications for the asset rather than what might be higher probability indications. Will it be tested in MS? If not, why not? What's the outlook for this molecule?

So I think BTK inhibitors are pretty entrenched in the oncology space, you're very well aware of that, from a heme perspective and are broadly used. We have taken and chosen the path of utilizing a BTK inhibitor in a multi-pronged approach in the autoimmune disease with rheumatoid arthritis, Sjogren's syndrome, SLE. Those are the patients being enrolled in our ongoing study. At the current time, we don't have any -- a plan to investigate it in MS at this time. Our focus is on Zeposia launch, and we'll continue to evolve there. And then if the data continues to emerge and dictate that we have to change our path and think differently, we will. But at the current time, we would like to see the data as it emerges from the autoimmune diseases.

So we're down to only 1 minute left. So we talked about some of the more visible, promising assets in late-phase development. But Bristol has a deep early and mid-stage pipeline. So what are 1, 2 or 3 molecules that we haven't talked about that maybe you haven't talked about in the past to investors that you look at and say, "Gosh, this could be big."

We touched on a few. So maybe I will pick one from all different phases. So certainly, we've talked about it, but in our view, it is a new entrant to the BMS pipeline, which is mavacamten, which we do believe is a very effective drug that we will hopefully get the submission and then approval for that drug for patients with obstructive hypertrophic cardiomyopathy, where nothing really exists today that targets the underlying cause of the disease. And then growing on that will be additional indications of the future. So that's something very, very important. Another one would be Reblozyl that we talk about, but we haven't talked today. But certainly, the next evolution of the data from the COMMANDS study as well as from the independent study in MDS and in myelofibrosis, respectively, will really be very important from the future growth perspective. We already touched on the protein homeostasis platform in the early phase, so I won't belabor that again. But certainly, in oncology, we do have a TGF beta inhibitor. We do have IL-12 that we continue to also keep an eye on as the data will continue to evolve and how we can do the combinations thereof. In the cell therapy space, we didn't get -- touch much today in this discussion, but certainly, ide-cel and liso-cel being the front runners. But how those will evolve from a combination perspective, whether it be in multiple myeloma or lymphoma, the next readouts that will be coming out in the early settings of lymphoma for liso-cel will certainly be triggering another inflection point for that particular therapy. So there are some of these elements that are critical to think of in addition to what we talked about earlier.

Great. We are out of time. So Samit, I want to thank you for a great and thorough rundown. And we'll continue to watch the many positive and exciting things underway in the Bristol pipeline as the years unfold. So thanks so much for your time today.

Thank you, Steve and Michael. It's always a pleasure, as always. Very informative for me as well.

Thank you.

Thank you.