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

[Audio Gap] to the Cowen conference. Representing the company is Samit Hirawat, who is Executive Vice President and Chief Medical Officer and the Global Head of Drug Development. So thanks, Samit for making the time to be with us. Lots to talk about, lots going on in the Bristol pipeline. So we'll jump right in.

Let's start with Sotyktu, which is off to just a terrific start in the marketplace for psoriasis. You're working on a number of other indications. Those are in development. Can you kind of order them relative to your conviction and/or the market potential? And just remind us where those additional indications for Sotyktu stand today?

Sure. Thanks, Steve, for the question. And certainly, very fortunate about the Bristol-Myers Squibb pipelines. And in terms of pioneering the way for the first-in-class TYK2 inhibitor, Sotyktu. First of all, great start, thanks to our teams who delivered on the promise of Sotyktu and a TYK2 inhibitor in moderate-to-severe plaque psoriasis. We've showcased the data in the past on the Phase II trial in psoriatic arthritis that paved the way for initiation of the Phase III trials in psoriatic arthritis that are enrolling as we speak. We also have shown the data in the Phase II setting in a randomized trial for systemic lupus erythematosus, the largest of its kind in the Phase II study with very promising data that encourage us to engage with the health authorities to design the Phase III program. And we actually launched the Phase III program in January of this year as well. We also had talked about the ulcerative colitis data 1.5 years back, where we did not have a proof of concept. And so we need to retest the hypothesis. And those studies in Crohn's disease and ulcerative colitis are ongoing. Those are Phase II studies. And as we have communicated before, we are looking forward to seeing the data in the first half and the second half of this year, respectively, for Crohn's disease and ulcerative colitis and we'll provide an update on those. Beyond that, there are a couple of other programs that we are working on, and we'll be -- and you know the alopecia areata Phase II is already on ClinicalTrials.gov. We are enrolling in that trial. And then there is one more indication that we will be able to talk about later this year once we have initiated that trial.

Okay. You mentioned when starting to talk about Sotyktu that it's first-in-class, obviously, it is. There's a number of competitors coming, both within the TYK2 space, but also kind of adjacent spaces. Maybe you can just tell us why Sotyktu is not only first-in-class, but will be best in class?

We do believe it's -- well, first of all, by default, if you're the only one, you're the best in class.

That's true.

So that's the beginning point. If you think about it now, the specificity of it, downstream effect, it's IL-12, IL-23 and interferon. These are the 3 cytokines we hit. And based on the science that evolved from there is why we pursued the individual indications, interferon SLE makes perfect IL-23, IBD makes sense. That's why we are pursuing it. IL-12, IL-23, of course, made sense for psoriasis. We pursued that psoriatic arthritis, we pursued that similarly alopecia areata, makes sense. If you think about the competition, there are 2 elements to it. One is in the oral space, one is the biologics space. In the oral space, certainly, there are other TYK2 inhibitors that are in development. Now of course, I think competition is good. Innovation is good. Anything that can come and be better is certainly welcome because it is important that we keep the patient in the front and center. And if something that helps the patient more, we're all for it. However, whatever comes next, whatever the competition is, needs to be able to demonstrate that it is better than what is out there. We are no longer in the space of science and drug development where mediocrity should be accepted, where similarity or similar me-too drugs are going to provide better outcomes for patients. So we need to see what is better. And so it is for the next generation of molecules to now prove that they are better or differentiated and we'll look forward to those data. Similarly, for injectables, I think are they going to be specific to IL-12 or IL-23 or interferon or promiscuous as an multitude of targets that they're hitting? And again, dependent on that data, again, it will be good to see where they belong with -- as it relates to Sotyktu. I know that some data has been talked about this morning from an IL-23 perspective. I just heard about it. I didn't see it. And it will be interesting to see when the data released, what they really mean and what the impact is and where they fit in the overall treatment landscape.

Okay. Maybe we can move to another recently launched asset for Bristol and that Zeposia. This is another product which will, at some point, get competition in the GI space. Talk about that dynamic. And this is another one where you feel -- suppose you still has an opportunity to be the leader.

Yes. So remember, Zeposia as an S1P modulator, it's about 2 indications right now. Multiple sclerosis and ulcerative colitis. The study in Crohn's disease is ongoing. We did have an impact. We talked about it because of COVID and then geopolitical situation that goes on. And so certainly, we are enrolling that study, and we are hopeful that we'll be able to get that completed soon. There will be competition, especially in the ulcerative colitis space as the next S1P modulator comes into the marketplace. We believe we do have differentiation still. If you think about the label, and we'll have to see what the label ultimately comes out for that competitor drug. If you think about the first-dose monitoring, we don't have that. And so that's an important element of that. And having more than 1 indication certainly helps in terms of continuously establishing the profile, generating the data and providing the safety updates, et cetera. So looking forward to what comes next, and we'll continue to evolve from that perspective. Certainly, from a commercial perspective, this is an important year for Zeposia as well as we look towards the growth trajectory for Zeposia in that marketplace.

By the way, I should have mentioned, should you have questions along the line, please just raise your hand, and we'll call upon you. So from the drug development standpoint, not the commercial standpoint, but from the drug development standpoint, how do you differentiate Zeposia and Sotyktu in the GI space?

So I think it is all going to be data dependent. For Sotyktu, as we spoke just a little bit earlier, we do not have that proof of concept to showcase the remissions or outcomes in terms of disease outcome, in terms of patients with ulcerative colitis and Crohn's disease. One of the hypothesis we want to test is, is higher dose going to be better in terms of causing a leading to the decrease in the symptomatology and increasing the clinical remission rate for ulcerative colitis? We are testing that hypothesis. Now on the flip side for S1P, we convincingly demonstrated the impact and the clinical remission rates that we saw in ulcerative colitis. We have to repeat that experiment for Crohn's disease. But in general, those diseases track quite well with each other, but we have to still wait for the data to see if we can get that in the label when the data reads out. But the GI space is bigger than IBD only. Remember, cendakimab is a third molecule that we have, which is in eosinophilic esophagitis, upper GI. We do believe that it's a differentiated molecule. It's an IL-13 inhibitor. It inhibits both isoforms of IL-13. Now of course, the question is what else is out there and how is it going to differentiate itself. So there is Dupixent, IL-4 inhibitor, which also indirectly inhibits IL-13 but only R1 isoform. R2 isoform is important from a remodeling and fibrosis perspective, in addition to the information that occurs in this disease. The Phase II data were very strong. And so we are right now enrolling the esophagitis trial Phase III study When it reads out, we are hopeful that this will be the second drug that might be available to patients with this disease.

So you pretty much already answered this question. But when you step back and look at EoE, what is the unmet need that Dupixent currently is not meeting? So is the mechanism of Dupixent not giving the full response that you would expect from cendakimab, is that the answer?

That is our hypothesis and our scientific rationale to pursue IL-13. There are 2 elements to it. One is the inflammation and second is fibrosis, right? So what we've seen thus far from the data perspective, certainly, there is an impact on inflammation with Dupixent that we've seen that. What we saw for cendakimab is in a small study, but Phase II randomized trial is also endoscopic evidence on improvement in that fibrosis. which should translate ideally into decrease in the dysphagia days, and that is one of the elements that we have included in the study to be able to measure the decrease in the dysphasia days. And if that is achievable, that is a big unmet medical need that we will be able to serve.

Okay. Dysphagia, obviously, meaning lack of appetite or days...

Yes, you can't eat, right? Because we are -- there is the esophagus that is constricted, so you can't really swallow and get that...

Okay. So cendakimab to the best of our knowledge was also in development for atopic dermatitis and that is no longer. So why was that decision made?

So we certainly want to be very mindful not only of the landscape but also how we differentiate ourselves as we get into the landscape. We talked about it earlier that it makes sense to develop drugs, which are differentiated, that are not necessarily going to be me-toos or not going to be something that just is going to provide miniscule improvement on what are established therapies, available therapies. In atopic dermatitis, we set our bar in terms of, first of all, readout of the primary endpoint of the clinical trial. But then for development, we made sure that we set a bar ourselves to say we need to be better than what is out there. And it's a very crowded field in atopic dermatitis. Lots of drugs have come through just recently. And so as we look at that data in that landscape that is out there, -- we didn't think that there is enough in that data set to showcase our differentiation and something that will stand out. And as your question was before, that will really meet the unmet medical need in that disease. So it does not make sense for us to continue to invest in that indication, but much rather we would focus on something else because our pipeline is quite full and healthy.

Okay. Questions from the audience? So let's move on to milvexian perhaps the most important drug that you might be developing. So maybe you can update us on where you stand in Phase III?

Sure. So if you call milvexian, a very important drug in the overall pipeline in cardiovascular space, Factor XIa inhibitor. We have initiated a first trial with Janssen in the secondary stroke prevention. That is a 15,000-patient study, 25 milligrams BID dose based on the data that we had collected in the Phase II. The second and the third study, which we have declared publicly, will be starting within this half of the year -- within the first half of the year in atrial fibrillation and second one in acute coronary syndrome. Acute coronary syndrome, that is in -- with the background therapy of antiplatelet agents, similar SSP to whereas the third study in atrial fibrillation is the single agent versus apixaban, that's what we recently announced in our press release.

Okay. Are there any meaningful differences between the Phase III studies and meaning such as enrollment criteria, safety endpoints, patient subgroups compared to the successful trials in Phase II that you've already run?

Not in a major way. We are still looking at the similar endpoints, not only from a safety perspective, but efficacy as in prevention of ischemic strokes in the Phase III trial. So not in a major way. So we are trying to replicate and improve on the data that we have seen in the Phase II. Safety is going to be a very big component today because these patients are not treated with anticoagulants because there's a bleeding risk with anti-platelet agents being on board. So that is going to be a very, very important element for this development.

So you announced these free trials, 1 initiated, 2 to come. Paint for us the picture of what the ideal outcome is in each one? And if you could add any numbers that would be phenomenal?

Yes. So too early to add numbers. We haven't really declared the statistical analysis plan for these trials, But you can imagine these are thousands of patients. The first study is 15,000 patients. And the other 2, we'll talk about once we have declared the overall design as to what the dose is and what the overall sample size is. And the outcomes are pretty simple and straightforward as such. If you think about secondary stroke prevention, the outcome would be from an efficacy perspective, prevention of ischemic stroke, similar to what we have tried to show in the Phase II study and of course, the outcome from a combinability and safety perspective not having fatal or serious bleeds as we combine to the background therapies. Same is the outcome for acute coronary syndrome, again, preventing the events -- cardiac events in that particular study. And then same to -- same as atrial fibrillation, we've seen that with apixa -- with apixaban already in Eliquis trial, so replicating those endpoints. But here, we have an active competitor. So certainly, the bar is high, but we are hopeful and confident that we'll be able to achieve that as we launch that program. But we are not getting into the specifics of the statistical design and the superiority margins that we've set for ourselves.

So 2 of the 3 trials have an active comparison. Sometimes, we witnessed situations where when drugs get to Phase III much larger population, much more heterogeneous, lots of centers, global, different standards of care. And all of those factors or some subset of them leads the trial to have a different outcome than we saw in Phase II. That must worry a drug developer such as yourself that things aren't going to be perfect in Phase III. How did you guard against that?

So I think experience does matter in these situations, managing and what you've seen in the past that works and doesn't work becomes very important to replicate or dissuade from a team's perspective to not do. Here, we have 2 companies joining up our minds as we look at designing these studies as we did design these studies, we engage the regulators on both sides of the pond to get an input into the trial designs, agreeing on the overall statistical plan and what the endpoint should be. And as we look to the future, both teams are going to be really heavily engaged in terms of data monitoring and cleaning of the data so that we can raise a flag if we start to see things deviating from the norm. We will have DMCs in all these trials, so data monitoring committees, we are going to be paying attention to the evolving safety data as well. So they will keep us honest in terms of making sure that if they see a signal that we are aware of it and then we manage it. So those are all the -- any drug developer would think about any of these things. And we just have to ensure that the teams pay close attention to the enrolled patients that they're not deviating from what is written in the protocol.

This is another market where you have competition. How do you think milvexian stacks up against the competitors?

So it's difficult for me to really do apples-to-apples comparison because there are 2 different companies, 2 different drugs, 2 different trials that were conducted. You've seen the data that the competitor Bayer has presented as well as we presented. We do believe that we have a big therapeutic window, although it's BID dosing, but we have the advantage of a shorter half-life in a way. We do believe that we have the experience from Eliquis days of BID dosing. So many people have asked us the question is BID a disadvantage. We don't believe twice a day dosing is a disadvantage at all. And I think the overall experience of conducting these trials and being able to combine the brains of 2 companies does have its own advantages, I think. So it's hard for me to say ultimately where the cards will land and how they will ultimately showcase, but we are very confident in the overall plan. I know that our sample size is larger for SSP, we believe that statistical significance and clinical meaningfulness might require that sample size to be there.

Okay. Let me ask one more question about milvexian and then one on Camzyos, then I'll turn it to Mike for some additional questions. Remind me, did any Eliquis study stop early for either efficacy or safety? I know the vast majority of them worked out successfully, one, I think, did not. But did any of them stop early?

I don't remember, but it did, ACS.

Okay. Okay. On Camzyos, what is the development path from here? So it's on the market doing off to a constructive start. What's the development path forward?

So myosin inhibitor -- cardiac myosin inhibitor, Camzyos first approval, obviously, done with obstructive hypertrophic cardiomyopathy in the U.S. And then, of course, the second study has initiated now in nonobstructive hypertrophic cardiomyopathy as a Phase III in January. So we're looking forward to enrollment of that trial. We have a proof-of-concept study, Embark that is ongoing in patients with HFpEF or heart failure with preserved ejection fraction. And we'll look at that data later this year and see if that is meeting a muster to be able to then think about larger and longer plans. So we'll keep you posted on that. But those are the 3 major indications as we think about additional indications, we'll let you know, but those are the 3 major ones.

Let's turn to oncology and talk about Opdivo a little bit. Growth of Opdivo is dependent in large part now on success in adjuvant and neoadjuvant settings. Can you remind us where you stand with Opdivo [ in key ] tumor types in those settings?

Sure. So obviously, lots of approvals already in our hands. And certainly, Catherine is here. So later on, if anybody wants questions on the market opportunities and how we are performing, Catherine will be able to answer those questions as well. With that said though, what -- from what I know and I understand from my commercial colleagues, overall, Opdivo is doing really well from the GI indications perspective as well as continuing to make progress in the lung cancer space because we have the new adjuvant indication. So certainly making progress over there. Melanoma wise, obviously, not only because of the combinations that we already have with ipilimumab in the past. But because of Opdualag, even continuing to really do very well in that situation. Now of course, as the next iteration to that, we are looking forward to the readout of the non-small cell lung cancer trials. 73L is in the nonresectable stage III non-small cell lung cancer, that's still to read out. And then 77T, which is our periadjuvant study, where we will have the new adjuvant and the adjuvant parts in the study. So we're looking forward to those readouts. While they don't contribute in the next 2 years, but beyond that, that might be very interesting and important as well.

So your competitor recently posted positive periadjuvant...

Exactly.

Is there any difference in trial design that are notable?

They're very similar, I would say. And plus, remember, we already have the new adjuvant covered. So now what 77T will add is the adjuvant portion to our already established new adjuvant position.

Are there -- is there any hope left for a checkpoint inhibitor in prostate cancer?

Look, we have our own study that will -- that is still to read out 7DX. So we'll wait to see what that data will tell us. But I think, we have to continue to hope, and we have to continue to learn from the science that we do. And if it doesn't pan out, if it doesn't work out, then we'll learn something more as to what the mechanisms of resistance might be over time as we look into the deeper into the biomarkers. And then we go back to the drawing board and say, which other drugs should we be developing that comes in here. Remember, from a prostate cancer perspective, our protein degradation platform has given us a new molecule that we are quite excited about, the androgen receptor ligand dependent degrader. So we are developing that. That's in Phase I. We are starting to see the data that's quite promising. We are hoping to have a proof of concept done by the end of this year. And then next year, hoping to bring it into late-phase development as well.

You mentioned Opdualag, which has been performing well in melanoma. Phase II data in frontline lung cancer coming this year. Can you help us -- help shape our expectations for that read out? What data are we actually going to get? And how important is it to lung cancer?

Sure. So overall, if you think about the Opdualag program, the first indication, yes, we have that covered from an FDA approval perspective. We have finished enrollment in the adjuvant study of melanoma as well. Over the next couple of years, we'll see the readout as well. We have an ongoing Phase III study in colorectal cancer MSS. That should finish enrollment this year, and next year, we should be able to see the data. In non-small cell lung cancer, we have a randomized Phase II study that is ongoing, looking at Opdualag plus chemotherapy versus nivolumab plus chemotherapy. So it's a randomized Phase II study. We are using that to, number one, answer the question of contribution of components. So what does LAG3 add on top of a PD-1 plus chemotherapy. This will also give us a good understanding that if the data do pan out and show superiority to the doublet of PD-1 inhibitor plus chemotherapy, then we can go to Phase III in a 2-arm trial of Opdualag plus chemotherapy versus the established PD-1 inhibitor that is KEYTRUDA plus chemotherapy. So that's the intent, but we have to wait for the data to read out.

How important is the adjuvant melanoma trial to Opdualag's future?

I think it's a critical element in the overall Opdualag development. And I think LAG-3 has shown great promise in the metastatics. So I think it's quite natural to progress it further into the earlier setting to hopefully see an outcome that benefits even more patients because melanoma patients, yes -- and over the 10 years, we made a lot of progress, but still an unmet medical need from a long-term outcome perspective.

What other fixed-dose combinations are you exploring without nivo.

So right now, we have lots of combinations ongoing. And depending on how the overall efficacy profile evolves from those combinations, we can think about combining with other agents. But we have not declared anything yet from an FTC perspective or FDC perspective as to what combinations we are pursuing as a fixed-dose combination, we have not declared that.

Let me just interject me. Is it likely that data dependent that you will continue to pursue the strategy with [ HAY ] stores is that -- was it one and done?

Whenever possible, we will.

Okay. One of the potential combination partners is anti-TIGIT, what is your thought on TIGIT as a target given the data we have to date?

I think is jury is out on TIGIT. It's not a proven mechanism yet that it doesn't work or it works. We saw some interesting data over time from several players in the field. Phase IIs have panned out. But I think Steve's question early on, as you go to Phase III, things don't necessarily work out the same way as they did in Phase II. Now why does it happen? Sometimes the heterogeneity of the tumor. Sometimes it's because we try to do too much in the Phase III because we wanted to go for a larger population. Sometimes we select different patient populations. Sometimes it's a dose, sometimes it's schedule. And that data has not really been shared thus far from the studies that have completed. So we'll have to wait and watch out for them. One thing that is different for us, we looked at the monospecific TIGIT first in combination with nivo plus epi. And we saw that -- number one, we were late, but number two, we saw a safety signal. So we said, okay, we'll stop that. But we have the next TIGIT, which is a bispecific. We do believe that there is -- there are other pathways that open up once you're blocking TIGIT. While we have not declared what the second target is, it will be interesting to see what that does as it shuts down the overall pathway and can that lead to better outcome. And so we have the single agent Phase I ongoing. We've just initiated the combination as well with nivolumab, and that data when it reads out will tell us more about the TIGIT. But TIGIT is an interesting target. We can't give up yet on that.

When can we expect data from the [indiscernible].

It will be next year, definitely not this year.

And your comment on the Phase II, not Phase III is an interesting one.

That was Steve's comment, not -- I just added to that.

Definitely notable in the TIGIT field. Back on the topic Opdualag in the Phase II lung cancer data we're going to get. Is that trial design in such a way that you should have more or similar confidence relative to this potential issue of moving to Phase III? And do you view this as an issue that's specific to IO or just sort of clinical trial.

No, it has happened many times that Phase II doesn't translate to Phase III or the Phase II data historically speaking. And if you think about it, what happens in the Phase III, it dampens out in the Phase III because of all the reasons that we've already spoken about. And so from an Opdualag non-small cell lung cancer study, if the data does read out, we've set ourselves some bars that we need to achieve a certain threshold to progress to Phase III, otherwise we don't. So we have to really live up to that promise of the Opdualag profile. But if we get that profile, then we proceed.

Can you give us a sense what that part might be?

No, not yet.

So let's move on IMiDs and cell therapies. How are you planning to position iberdomide and your other follow-on in it relative to Abecma.

So let's start with -- there is a complete differentiation in terms of what these therapies are. Abecma cell therapy, truly transformational, highly efficacious, leading to complete remissions as well as PRs. Started in the late line setting fifth line plus. Now we have data in KarMMa-3 in the third line plus patient population, looking forward to getting that to the patients soon. But that population is a set population, not everybody is going to be getting cell therapies. You need the right setup. It is still limited to the academic centers where patients can actually be treated, side effects are managed if they occur, et cetera. IMiDs are more -- it's a small molecule, number one. First of all, and CELMoDs are small molecules. So what we are thinking of iberdomide is a combination strategy with standard of care therapies to begin with. And that's why we are doing 3 Phase III trials, one for iberdomide looking at a combination with daratumumab and dexamethasone comparing to VELCADE, daratumumab, dexamethasone. So replacement of strategy, if you think about them. This is in the second line plus patient population, 1 to 2 prior lines of therapy achieved. For mezigdomide, which is a more potent molecule. That means it does have a liability that it can't be combined with everything. So we have to be choiceful. We are not combining with daratumumab. But we wanted to ensure that we do compare versus pomalidomide. So we have a study of pomalidomide, VELCADE, dexamethasone versus mezigdomide, VELCADE, dexamethasone. So here, we are replacing pomalidomide. And the third trial is also with mezigdomide is a replacement -- or rather add-on strategy with Kyprolis and dexamethasone. So Kyprolis/dexamethasone versus mezigdomide, Kyprolis/dexamethasone. Now if I were to bundle it all together, if you think about CELMoDs, in the second line plus space, about 60% of the patients are treated with 1 of the 3 combinations, PVD, VDD or with KD. so Iberdomide and mezigdomide actually captures that patient population. And then the next iteration on that later this year, what we intend to do is initiate a trial for iberdomide in the post-transplant maintenance space comparing it head-to-head versus Revlimid. We believe that could have a better outcome for patients. So once that study starts, we can take a deeper look into that as well.

Great. The last minute I'll turn it back to Steve to ask...

Final question. So you probably have a pretty good understanding of where investors think Bristol development will be, say, in 10 years. You have a lot greater knowledge of where Bristol book development will be in 10 years. What is -- what do you think will be the biggest surprise that investors are not appreciating now? Is it the breadth of the pipeline? Is it the capability of certain assets? What is that, that we don't know that will surprise us?

Tim will kill me when I say this, but it's okay. I think -- again, look, I'm a drug developer. So I know a little about the dollar signs. But what I do think is the least underappreciated. And this may not just apply to BMS, but everybody else is not much value is given to the early pipeline. If you think about our early pipeline, there are about 50 assets in development. We've publicly stated that we anticipate that over the next 18 to 24 months, we should have about 15 proof of concepts. And we've spoken about already that apart from the 9 newly launched products, we will have 6 in Phase III development new molecular entities by the end of this year. Beyond that, we've talked about CELMoD-282. We've talked about AR-LDD as a protein homeostasis platform outcome. We've talked about GPRC5D as a third cell therapy in our pipeline. We've talked about alnuctamab, all of them will enter late-phase development. So -- but I don't -- I think that -- for me, that's a surprise that it doesn't get the value that it should get, but that could be something that will be a surprise at the end of the decade or early next decade, that these all turn into major impactful transformation products.

That would be a pleasant surprise. And a fascinating conversation, Samit. I appreciate your time.

Thank you.

We wish you all.

Thank you so much.