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

I'm pleased to welcome Bristol-Myers Squibb to the stage. My name is Carter Gould. I cover U.S. biopharma here. I'm pleased to welcome Lynelle Hoch, President, Cell Therapy Organization for Bristol; as well as Wendy Short Bartie, who runs the Hematology and Oncology business. Welcome both. Thank you very much for joining us today.

Thank you, Carter.

All right. Great. So obviously, we've got a big day tomorrow -- a big day today in terms of [indiscernible] approval, but a big day tomorrow in terms of BCMA outcome. Briefing documents came out yesterday. Maybe Lynelle, just start with sort of your takeaways from the documents. Anything that surprised you and your level of confidence at this point?

Yes. So as you said, it's a big day and week for Bristol-Myers Squibb overall and certainly in cell therapy. And so starting with your question specifically around the ODAC, yes, we've had the opportunity to obviously review our briefing book and also on the competitors' briefing book. And I have to say, as we felt going into this week and where we sit today, we're extremely confident in the discussion that we will have with the FDA. We've been looking forward to this discussion. And if you remember, our auction date was in December. So we've been anxiously awaiting the opportunity to defend our data and have a good discussion, particularly about the question they have around OS. But just as a reminder, we have already successfully have approval for KarMMa-3 in Japan. We successfully navigated [indiscernible], which is actually the equivalent of an ODAC for Europe and resulted in a positive CHMP nod. And then also we've had approval in Switzerland. So we do feel very, very confident on the clinical benefit that Abecma can offer into earlier lines, one, because of our pivotal study with showing -- meeting our primary endpoint of PFS, but also we made the decision to make a patient-centric approach in our trial design by putting prespecified crossover for the trial of KarMMa-3, which did confound the results. We do work to be able to show and a have discussion with the Advisory Committee on our data to be able to show the clinical benefits and also to be able to show the actual impact of the crossover. We, of course, you asked this last night, and I'm sure it's the question on the minds of folks about the questions around early death. Again, we look very forward to the opportunity to show our data, particularly showing them the role of bridging and actually making sure you debulk patients and the benefit that has for CAR-T, but also really specifically showing in KarMMa-3 that the majority of the early death, those patients never received Abecma and the Abecma arm. So we do feel confident in the ODAC and the opportunity to have that discussion with the FDA and the advisory committee.

Okay. So on the back of that, assuming everything goes well on Friday and the forthcoming PDUFA goes in your way, how do you still feel about the long-term commercial competitiveness? It would be great to get the label expansion. But relative to legend out there, how are you thinking about your ability to compete still?

Yes. As you've heard on our fourth quarter earnings call from Adam and Chris and others, KarMMa-3 is a critical stimulus for our growth for Abecma for a few reasons, of course, because you move into earlier lines, larger population. But the other reason is this is where our profile will work hard for us. As you can remember, our overall profile, when you look at Abecma from an efficacy, safety and manufacturing, those attributes of safety matter as you move into earlier lines. We've heard this over and over again from TLs. So I do think our profile will work harder for us. We'll be in a much better and more competitive position as we move into earlier lines.

So I'm going to ask you the same question I asked you last night, and that is in terms of how you think about differentiation on safety, and specifically on the Parkinsonism relative to your competitors?

So I can't speak to because there's no head-to-head comparisons between the two drugs. But what I can say what I hear from TLs. TLs do see a difference in the safety profile of these two drugs. And I do think, as you move into earlier lines, that profile for Abecma will matter to physicians as they're making choices into earlier lines. Because you have to remember, these patients with multiple myeloma live for a very, very long time. They will be exposed to multiple lines of therapy. And therefore, they want to be very choiceful as you're pulling a CAR-T into earlier lines, on what's the tox profile you're going to be exposing them to and how that will impact them over the life of living with multiple myeloma. So I do think this is why we're confident in our overall profile.

Okay. We're going to come back to cell therapy in a minute, plenty to talk about. You also made some news yesterday around an update on the LAG-3 program. It was probably one of the more additional catalysts people are paying attention to on -- for Bristol, this first-line lung opportunity. Stock responded negatively, at least for a portion of the day. When we talked last night, you seemed much more positive on the outcome. Wendy, maybe outline kind of your takeaways from the data and why you're so positive here?

Thank you for the question, Carter. We're actually excited about the results. So let's take a step back. We conducted a very large Phase II study that really was designed to interrogate the question. What happens if you add LAG-3 onto a PD-1 in chemotherapy? And would you be able to get incremental efficacy over PD-1 chemotherapy? And we were trying to identify what patient population we could see the incremental efficacy and we're really pleased with the results of that Phase II study. In fact, we did identify a very important and sizable patient population, 20% to 30% of eligible patients that would benefit from a LAG-3 plus PD-1 plus chemo versus PD-1 chemotherapy alone. In fact, we're so excited about the data that our intention is to proceed with the Phase III study before the end of this year. And again, we think that this is important because while the bar is quite high when you consider PD-1 and chemotherapy, our confidence is high based on the data that we've seen from the Phase II study results.

Okay. And this group was prespecified?

This was a prespecified group, yes.

Okay. And maybe just put that then where that would sit in the broader, kind of lung portfolio for Bristol? What do you think?

Yes. So if you think about where Bristol-Myers Squibb is from a lung cancer perspective, we continue to be very committed to our Opdivo-YERVOY combination plus or minus chemo in first-line non-small cell lung cancer. With the recent acquisition of Mirati, we now have a targeted asset for KRAS non-small cell lung cancer in the second-line setting. And with the recent approval of our asset, Augtyro, for first-line RAS-positive non-small cell lung cancer, the ability to bring Opdualag plus chemotherapy to market in the first-line setting just allows us to continue to expand BMS' presence in the first-line non-small cell lung cancer setting. We know that the patient population is large. Some patients are appropriate for immunotherapy-based combinations. Others require targeted therapies to which their disease will be exquisitely sensitive. We're building out our portfolio to meet the spectrum of non-small cell lung cancer patients where they are.

Okay. So I know we're not going to define that prespecified group today. But at what point can we see the data or -- and then see the Phase III design?

And to be clear, we're not talking about that subgroup with that specified population today because this is a highly competitive market. And so we do need to kind of temper what we share relative to the competitive set, but you can expect to see the data sometime this fall at the latest.

Okay. Great. Maybe moving back to cell therapy. I alluded to it at the start. You do have the CLL approval in the very near future. Maybe if you just think about the line extensions here for Breyanzi and the ability to drive a continued -- another layer of growth, can you just talk about the opportunity there?

Yes. Let me first start saying, yes, today is our PDUFA day for CLL assuming approval today. We will be the first and only CAR-T to receive an approval in relapsed/refractory CLL or SLL. And this is extraordinarily meaningful. If you know the history of CAR-T, it's actually one of the first place where CAR-T was studied with CLL. But because of the nature of the disease and the function of the T cells, it's been very challenging for CAR-Ts to have success in showing clinical benefit across efficacy and safety. So we're extremely proud that BMS, and specifically Breyanzi, was successful in showing that clinical benefit and look forward to the opportunity to bring this transformation to patients. So when we think about CLL, and as you know, we've also have received accelerated approval and have PDUFA dates in May for follicular as well as MCL. When you look at the totality of those three and in addition to becoming unconstrained on vector, we really do see the opportunity to double the breast milk patient population, we'll be able to reach with our best-in-class frankly.

Well, when you think about that opportunity, so obviously, the label would expand. At the same time, we've heard from peers in the space that there are sort of capacity constraints at the academic center level. How can you continue to drive growth if it seems like the academic centers are going to, maybe be limited on how much more they will open up beds, et cetera?

Yes. So a couple of things there. First thing and foremost, we're looking to expand our treatment site footprint. So we're currently at 120 sites. We'll be at 180 by the end of the year, so expanding that footprint. The other key is making sure you drive patients out of the community into these treatment centers. So we also have put effort into our community sales forces to be driving referrals into this expanded footprint.

Okay. In terms of competitive threat from bispecifics here, how do you see that? We've heard, again, noise from peers that they're sort of nipping at the heels, certainly seeing that in myeloma, but at least in NHL, how you're thinking about that?

Yes. And listen, I think it's always great when you have multiple treatment modality and options because every patient can't receive every modality and every option that's available despite the fact that the indication might say so. I think what's key for us is reminding physicians a sequence and the importance of exposing patients to CAR-T in earlier lines because that is what we've seen, particularly data shown in multiple myeloma, that patients get the greatest long-term overall benefit when they're exposed to a CAR-T first and then on to a T-cell engager. I also think it's a little bit different in lymphoma. We definitely hear from physicians depending on if it's a more indolent disease versus a more rapid disease. So let's talk about large B-cell lymphoma. I think most physicians are very strong in their opinion, including the community that patients need to be exposed to a CAR-T. You have a very high CR rate and those patients are going to go on to potentially have a deep, deep, long, durable response. And in the more indolent diseases, you're going to see in follicular, I think it will be a more competitive dynamic between bispecifics and CAR-Ts and they'll be more selective in which patients receive a CAR-T versus bispecifics.

Maybe, Wendy, coming back to you. And as we think about the Reblozyl label expansion late last year, had a very strong 4Q. When you think about sort of the durability of that recent bolus, can you maybe expand upon that a little bit as well as the opportunity to maybe broaden the centers that you're in currently?

Sure. We continue to -- we expect to see continued growth into this year and beyond for Reblozyl in the first-line setting. So what we actually saw last year after the launch was rapid uptake in the first-line setting, both in the RS-positive and in the RS-negative patient population. Naturally, we saw an uptake faster in the RS-positive patient population, which makes sense because that's where the second line indication was approved, but we also saw growth in RS negative. Where we headed now? Our growth this year will really come from first-line RS-negative patients. That's the largest population. And specifically, we're focused on RS-negative patients with an EPO level of 200 and below. I think the other important thing to consider is while our initial launch was success with both, in the academic centers as well as in the community setting, we're really focused on driving uptake in the community setting because that's where the vast majority of these patients sit. More than 70% of MDS patients are treated in the community. And then I think in terms of expansion further this year, we're really going to be also focused on expanding our new user base. So right now, roughly 2/3 of our prescribers are physicians that were prescribing Reblozyl when it only had a second-line approval. 1/3 of our prescribers, which is exciting, are new to brand. But our expectations will continue to grow the new-to-brand prescriber base.

So it's clearly still early days in the launch, but sort of your view on duration and how that will evolve in further line setting relative to the initial label?

Yes. So I agree with you, it's early days of launch, but we've been committed since day 1 of this expanded approval to making -- we're educating our physicians on effective titration of Reblozyl because we know there were patients who titrated to the right dose. They're able to stay on therapy longer, which is really good for their outcomes. I also think you're going to -- and we continue to get our communities to hire certified nurse consultants as well as all of our customer-facing team. But I think it's also important to note that as we continue to drive uptake in the first-line setting, and we're getting patients with EPO levels of 200 or below or patients who have lower transfusion burden, you're naturally going to see the outcome of that being along the duration of therapy.

Maybe last question on Reblozyl. Myelofibrosis has taken a while to kind of get going. At this point, your level of confidence in sort of the time lines you've communicated. Remind us exactly what those time lines are and how you think about that incremental opportunity over the indications you already have?

We expect to see data from the independent study. That's the myelofibrosis study next year. And we are confident that our time lines are tracking consistent to what we've previously communicated. And we remain -- again, we remain committed and excited about the opportunity and anemia induced by myelofibrosis. We see a significant unmet need, and we know that Reblozyl will be an effective treatment -- we believe Reblozyl will be an effective treatment.

And recent competitive data and acquisition by a larger company doesn't change that view in your mind?

We still think that we have a strong place. I think the competitive assets that you may be referring to is intended as discussed to potentially be disease modifying, but only time will tell whether or not that's actually correct.

Okay. Maybe going back to Lynelle. One of the things we've seen certainly over the past 6 months is some sort of -- we refer to it in certain way and print as sort of a land grab and sort of the CD19 into autoimmune. You guys have been out in front. But talk about Bristol's effort right now there and how you sort of stay ahead of the competition here and to the extent that you think the importance of being first to market here?

Let me first just start with, "Why is it so extraordinarily exciting of bringing a CD19 CAR into autoimmune?" So if you've had the opportunity to see Georgette's data, Georgette's data was the data that kind of rocks everyone's world. The idea that you could give a severe lupus nephritis patient an opportunity to have a deep, durable treatment-free response after one infusion of a CD19 targeted CAR was extraordinary. He just showed a New England Journal update and showed that the patients are continuing to have deep durable responses. He's also expanded that into other B-cell-mediated autoimmune disorders and shown that same deep, durable treatment-free result in diseases like myositis and scleroderma. And so for us, we're extraordinarily excited about the opportunity. We also are in a unique position. We're in a unique position because we have a best-in-class CD19 construct in Breyanzi that now we have put on an optimized manufacturer process, which is now our CD19 NEX T program. And I'd say that we're extraordinarily excited about that because we've had years of experience of understanding the overall profile of our CD19 construct, both from a safety and efficacy, and we also have a very strong understanding of manufacturing process. And so this experience and the capabilities we have in cell therapy along with our depth of experience and understanding of autoimmune puts BMS in a unique position to lead in this space. And we're super excited as well that our lead PI, Georgette, which makes it even more exciting to be working with a world-renowned thought leader in the space as we accelerate our program. So yes, it's a crowded space, anytime you see transformational results, anytime you see a potential of bringing a potential cure, I mean, obviously, early, early days to places and diseases that were considered incurable. You're going to get a tremendous amount of activity and excitement from the industry, and we're excited to be one of those companies that we think is well positioned to lead based upon, I said, the constructs, the thought leader that we're working very closely with as our lead PI as well as our deep capabilities across CAR-T and autoimmune.

And any key lessons from the CD19s, the BCMAs and the [Technical Difficulty] importance of being first to market or other aspects you highlight?

We think being first to market is really, really important here for a couple of reasons. Unlike when we're treating in cancer, we're dealing with in an incident space, right? So you're dealing with incidence-based. If you were able to show, depending on how these profiles emerge through their pivotal data, if those profiles look as we are seeing in the early data and you're seeing these types of responses, you're going to be dipping into a prevalence pool. So you're going to be dipping into a much larger pool of patients. So that's why we think it's extremely important be one of the very first companies into the space and being scalable. And that's why we have a huge focus across both of those dimensions.

Okay. And as we think about those individual indications, any sense on sort of time lines to data and maybe delineate the individual indications you are going after?

Yes. We don't get into the specifics just to say that we're going after all four populations as such [Technical Difficulty]. We have [Technical Difficulty] INC and MS, and we're also recruiting there as well. So, again, our indications that we're currently recruiting are SLE, [Technical Difficulty] scleroderma and MS. All of them are actively recruiting. We do hope to show data later this year.

I guess one of the other questions we get all the time is, given we've seen the challenges in oncology, then potentially massively expanding the population, how are you going to be able to keep up with that? How is the field going to be able to keep up with that?

Yes. So there's a few key things. One, there's been significant advancements from our first-generation autologous programs to our pipeline, and that comes mostly in two areas. One, [Technical Difficulty] technology on vector, which means that you have high yield vector solutions that make vector a non-issue moving forward. Secondly, and most importantly, is fully automating your manufacturing process end-to-end so that you actually are able to scale because you take less footprint in your manufacturing buildings when you actually are fully automated, and it actually helps you with turnaround time and speed to patient.

Okay. Maybe, certainly something you can both talk to is sort of how you see the evolution of the multiple myeloma landscape. Certainly, in terms of your longer-term projections, a big part of that is the CELMoDs that are potentially going to be launching in the back in the latter half of this decade. But I think from the outside looking in, you have a lot of different pieces that potentially could fit different segments, and it's been challenging for, I think, for investors to figure out, okay, well, that asset is going to go there or this asset is going to go there. Meanwhile, CAR-T could be an answer to a lot of those different segments. So...

Maybe I'll start and I'll bring Wendy in. I think when you think about multiple myeloma, it's a highly fragmented disease, treated very different ways for those different patient populations. And we're really proud that we have multiple different types of modalities that can treat different patients' needs across the journey of multiple myeloma. And so yes, CAR-T gives somebody a onetime infusion, a longtime treatment-free, which is certainly liquid gold to a patient when you think about the long time that they're going to live with the disease. But there are many patients who cannot receive CAR-Ts and also CARTs in complement and sequencing and potentially combinations are also what we're exploring with CELMoDs with T-cell engagers. So the fact that we have a full portfolio means we're going to be able to treat more patients and address more needs in this very insidious disease. So for us, we feel very proud of our overall portfolio. I don't know, Wendy, if you want to further complement on the CELMoDs and the T-cell engager.

Yes, I would agree with you on that. If you kind of start at the beginning of a patient's journey with multiple myeloma, when first diagnosed, most will get a stem cell transplant. And after they get their transplant, if successful, they'll be treated with maintenance therapy. And historically, that's Revlimid. What we believe iberdomide, one of our CELMoDs, would be an appropriate choice for those patients because we know that iberdomide is more specific. We know that it's more potent and more efficient than Revlimid. We also know that the side effects profile is better than Revlimid. So it becomes a really important option as a maintenance therapy for patients. And the other thing we know about iberdomide relative to Rev and Pom is that it works after patients have actually either not responded or progressed on Revlimid and Pom. So we know that it's a more effective agent. Beyond that, if a patient gets a stem cell and they don't respond, then it opens up a myriad of opportunities, as Lynelle mentioned, cell therapy if appropriate, but you will still have some patients that are not able or choose not to go to cell therapy centers to be treated with cell therapy. You may have some patients who just want to be treated in the community by their physicians. And again, CELMoDs are an important option because they're oral and they're easily combinable. I think it's also important to know, and Lynelle mentioned this, fortunately, patients with multiple myeloma are living longer. And when they live longer, there is a greater probability that their disease will ultimately progress on a current therapy and there will be more options. So we see CELMoDs being critically important and we do have bispecific development as well. And we believe that our bispecific [indiscernible] is going to be a next generation with enhanced efficacy over what is available today. So I couldn't agree with Lynelle more. I see the role for cell therapy and bispecifics as a bridging therapy to cell therapy, as maintenance therapy, and as part of combination as core therapy in the future.

If we come down to the last minute, I wanted to leave a question for both of you. You both have a lot more insight into what's going on internally at Bristol, the trials, the platforms, how do you guys see the market? What do you think is going to be the biggest surprise over the next 5 years across the oncology and cell therapy business?

Let me just say, I think it's an extraordinary time for BMS as we kind of move the next chapter at BMS, and we have an extraordinary pipeline, and we have a bevy of new products that we are launching around the world, and we're quite excited about the opportunity that presents itself in front of us. And when I think about the next 5 years, and obviously, I'll go back specific to cell therapy, listen, if we can bring a promise of a deep durable treatment-free remission with one single infusion to diseases in autoimmune disease, I think that will just be an unlocking a promise that will be just extraordinary.

I agree. I think the promise of cell therapy and autoimmune disease is huge, but I'm also incredibly excited about a recent acquisition of our recent acquisition of RayzeBio. Through that acquisition, not only do we get an asset, but we get an IND engine and a manufacturing capacity in one acquisition. And I think the RayzeBio radiotherapy platform complements work that's now is leading to the work that they do with cell therapy platforms. I'm also incredibly excited about the SystImmune Co-Promotion, Co-Development opportunity. Again, it's an antibody drug conjugate that allows BMS to further entrench itself potentially in lung cancer as well as into breast cancer. So I think there's a very, very bright future ahead for BMS.

We'll have to leave it there. Bristol, thank you very much and best of luck.

Thank you.