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

Good morning, everybody. I'm Terence Flynn, the U.S. biopharma analyst at Goldman Sachs, and we're very pleased to have you join us this morning at our Virtual Healthcare Conference. Today, from the company -- from Bristol-Myers, we have Chris Boerner, Chief Commercialization Officer; and Samit Hirawat, who is Chief Medical Officer. Thank you both for taking time out of your day to join us this morning. Really appreciate it. Again, I have a lot of topics to cover today, but I think one that's obviously front and center for most folks is the recovery from the pandemic.

So maybe, Chris, I thought you could kick it off and tell us a little bit about what you're seeing with respect to the recovery trends in kind of your key end markets here, both in the U.S. and then also outside the U.S.? And how has May been stacking up versus April?

Yes. Thanks for the question. It's great to be here, Terence. It's good to see you. I think what I would start with is just that the fundamentals of our business continue to be very strong. And I would say that's true for both the base business as well as the launches. I'm sure we'll have a chance to talk about those. The impact of COVID continues to be very product and, frankly, market specific. In general, what I would say is that conditions continue to improve really across most of our major markets and programs. So we're still largely trailing the pre-COVID levels. Remember, the main impact that we have seen with COVID was twofold. First, it was decreased new patient starts, and we really saw that across therapeutic areas, particularly acute, as we've talked about in oncology. And then second, we saw a reduced in-person engagement in terms of field employees. And again, that was true across markets, but particularly solid in oncology. What I would say is, since the first quarter, we have seen some improvement. Total oncology treatments have improved, though they're still trailing pre-COVID levels. We've seen IO demand has improved about 3% to 4% since the first quarter. Similarly, you continue to see new patient starts to improve really across markets that's been particularly true in a market like cardiovascular. And likewise, we've seen some improvement in terms of in-person engagement. Some markets like cardiovascular are almost back to pre-COVID levels. And notably, we've begun to see some improvement in oncology. So I think that, in general, we're starting to see real improvement. And the interesting thing coming out of COVID is, I think, there are a lot of learnings that we've taken away from this. Clearly, we're going to be engaging with customers in a digital way going forward. We believe it's going to be a kind of hybrid model of in-person and digital engagement, but that's going to be with us to stay. And what I can say stepping back now is we're starting to see some improvement as I'm incredibly proud of how the teams have performed. We've launched 4 new products during COVID, and we've established market-leading or competitive share of voice in all of them. So I think it's been good, and we've learned a lot along the way that we're going to take going forward.

Okay. Great to hear. Maybe just one follow-up. On the cancer side, can you quantify how close you are to pre-COVID levels now in terms of diagnosis in some of your key areas?

Yes. We had seen about a 10% to 15% decrease in new patient starts coming in to the beginning of this year as a result of COVID. We're still running between 5% and 10% below what we saw pre-COVID. But certainly, the trends continue to point in the right direction, and it's variable by market and even within institutions. So we're seeing a little bit more of a rebound in the community setting than we've seen in the academic setting. But by and large, the trends in the right direction. And obviously, it's something we will continue through the remainder of this year.

Okay. Okay. Great. And then maybe just Eliquis, kind of similar type question. I mean, again, I think that's been faster to come back here. And obviously, last quarter, you saw a tremendous growth here, a lot of momentum for that franchise. So again, are you expecting that to continue here through the balance of the year? And then what's been the key driver?

Sure. Well, we're obviously very happy with the global performance of Eliquis. As you said, in the first quarter, performance was very strong. That was a mix of very strong demand trends across key markets in the U.S. For example, we saw about 11% TRx growth. We saw about 14% pill growth, and we saw similar strong dynamics across most of our major markets. Remember, one thing about the first quarter, though, is that we did see a onetime true-up of the Medicare coverage gap to the tune of about $160 million. But even if you take that aside, the fundamentals in the first quarter were very strong. And as we look forward, I think those fundamentals are going to continue to be strong. In the U.S., for example, our OAC and new-to-brand share is roughly 62%. It's growing. Importantly, that new-to-brand share exceeds total brand share, which suggests there's still room to grow there. And certainly, we're seeing similar dynamics take place outside of the U.S. We're the #1 OAC in 13 markets. And we've got key opportunities to grow in some of our larger markets like France and Germany with Eliquis. And that growth, importantly, is going to be coming from both NOAC share growth and OAC share growth. So it's high-quality growth as well. So our strategy on Eliquis is going to remain unchanged. We're going to continue to leverage the best-in-class profile that we have with this product, and we're going to be very disciplined and stepwise in how we approach growing this product. But net-net, as you alluded to, we've got a very strong tailwinds by this product.

Okay. Great. Is there any reason why that -- you said 60% plus new-to-brand share. I mean, any reason why there'd be an upper limit on that? Or do you think that would just keep marching higher here?

Well, we get that question a lot. Obviously, to the extent that you're growing within the OAC class, the upper limit would be what is your Warfarin share that you can take from. Right now, Warfarin share is running about 12%. So what is the floor on the Warfarin? I think that, that's something that remains to be seen. What we have seen throughout COVID is the willingness of physicians to move away from products like Warfarin because of the reduced monitoring requirements when you go to a product like Eliquis. And so far, we're seeing continued growth in the OAC market. So our ambition from a commercial standpoint is to continue to drive share amongst the NOACs and the broader OAC class.

Yes. Okay. Great. I guess, Samit, over to you now. Obviously, Factor XIa Inhibition is another important mid-stage pipeline program. You guys are partnered with Johnson & Johnson. Starting to get some more focus now that we're approaching some of the first Phase II data here this year, and I know you have a second study reading out next year. Maybe, again, just when you think about the mechanism and the biological pathway, why is targeting Factor XIa potentially better than targeting Factor X? And maybe what's the basis that gave you guys the confidence to move into these 2 Phase II trials?

Sure. So if you think about from a mechanistic point of view where Factor Xa sits in the coagulation pathway, the cost for both intrinsic and extrinsic pathways [ committed ] whereas Factor XIa sits on the intrinsic pathways, which provides an opportunity to really up the anti in terms of how to give probably similar or better efficacy and also then try to see if you can have a better safety profile from a BTE perspective. So taking those 2 into account, we needed to find a better agent to give us that opportunity to up the game in terms of efficacy, safety and look at it holistically. Now in general, the way these agents are tested for anti-coagulation and BTE perspective, bleeding perspective is you do studies for a single agent as in -- such as the [indiscernible] study that we conducted as well as the second study that we are doing because it's important to keep in mind what's the background therapeutic patients get in some of these indications. So for secondary stroke prevention, we have the combination of Factor XIa Inhibitor plus, the pure anti-platelet agents, which are the standard of care in that population. And that's the reason for the conduct of the studies, to find that safety efficacy profile, but more importantly, to find the dose. And collectively, the two studies will then define on the overall development path for Factor XIa is going to be. And as you said, we are at that stage to now start to look at the data and see how to progress further. I'll just give you my perspective. As you mentioned already, we have seen the first Phase II data for the total replacement study. And I have to say, we are happy with what we've seen. We've compared that to enoxaparin, and the overall profile certainly is something that we are very pleased with and going to continue to work with our partner to see where we take next as we look forward to the readout for the second study.

Okay. Great. And so in that Phase II data that you have in-house now, it sounds like you're pleased with it. So does that also reflect kind of the safety profile? I mean, is there any inkling that you are seeing lower bleed rates than the standard of care, but then maybe also Eliquis?

Right now, I'm not going to get the specificity of the data because that is going to be presented later this year. But what we can say, the study delivered exactly what it was supposed to. So if you think about -- what we were looking over here is looking at the overall totality of the data of safety efficacy as well as to find the right dose, and I think we've got a good idea around where we are going to be approaching. So I think those are things to be kept in mind. I mean this was not a study designed to compare ourselves with Eliquis. This was a study designed to look at Factor XIa versus enoxaparin, which has been the standard for such studies that have been done in the past as well. So that's the comparison that we look at. And certainly, overall totality will be looked at again when we get a second study readout.

Okay. Very helpful. And then maybe just remind us on that second study, what's kind of the key parameter that you're going to look at? I know it's on top of background therapy. Eliquis, I believe, you can't add Eliquis to background therapy in that setting. So how are you thinking about triangulating what you'd like to see from that second study?

So I think major difference between the 2 studies are 2 differences. One, in the totally replacement study, the dosing is about 10 to 14 days for safety, whereas in the second study in the SSP, it's 3 months. So we are going to be able to see the longevity of the dosing. And from a safety perspective, 14-day dosing or 10- to 14-day dosing versus the 3-month dosing, what the difference [indiscernible]. Second, this is a single agent, whereas the other one has dual platelet agents, plus platelet -- dual anti-platelet agents plus anti-Factor XIa. So looking at that safety profile is going to become very, very important. And that's how the 2 studies will serve very well for each other to pick the indications of the future where we can go with either a single agent or the combinations thereafter. But having the ability to then target now the weakness side and [indiscernible] side will then be coming [indiscernible].

Okay. And then maybe I have one for Chris. But first, just how would -- where would AFib fit in the development program here as you think about that indication? Because I know you aren't doing a Phase II trial there, but is that something that you could expand into here? Or how are you thinking about that indication specifically?

We have not ruled in or ruled out any of the indications. I think everything is on the table. Ultimately, collective data assessment of the 2 trials will define what 1, 2, 3, 4, 5 indications that we will go after. So AFib is not ruled in or out at this time. So -- but again, both our partner, J&J and us will decide together what indications we should pursue. So more to come on that, not yet for prime time.

Okay. Okay. Great. I guess, Chris, just to you to follow up there, from your perspective, where would this fit in the paradigm and from a commercial perspective? Obviously, Eliquis sets a pretty high bar. But as you think about this as a follow-on product to Eliquis, how are you thinking about positioning this based on what you know today?

Yes. I mean obviously, we need to work through the 2 Phase II programs that Samit just mentioned, and that's really going to inform the full development program. Eliquis does set a high bar in the AFib setting. But I think it's important to also recognize that there still is unmet need in the cardiovascular space, largely in 2 areas, which is, first, secondary events. That's why we're doing the secondary stroke study. And then second, achieving high efficacy while avoiding new toxicity. And we still, even in spite of Eliquis' performance versus existing, not only NOACs but OAC, we do still hear physicians talk about paid rates. And so there is an opportunity to continue to improve upon existing therapies. But where this exactly fits in from a commercial standpoint, that's going to be data-driven, and we have to see the outcome of the 2 Phase II studies to better be able to [ inform ].

Okay. Okay. And then maybe just one last one for Samit. What -- is there a venue you guys are targeting for that full data? I know there's a number of cardio conferences. I think European Society of Cardiology is like August, if I'm not mistaken. Is that the most likely venue?

This is a [ stake ] that was conducted by J&J, although the decisions will be made together, but I don't have the specificity at this time [indiscernible].

Okay. Okay. Great. Understood. Great. Well, maybe moving on to immunology. This has been another recent big push for the company here is to bolster your presence in this space. Obviously, you have the Zeposia approved for multiple sclerosis. You recently received the label expansion for ulcerative colitis. And I know you have a number of other pipeline assets here as well, including TYK2 that we'll talk about later. But maybe just, Chris, from your perspective, give us an update on where your GI footprint sits right now. I'm sure the organization is ready for this UC launch. But then maybe just walk us through the early dynamics here, anything we should consider as we think about the ramp of this product?

Yes. Terence, first, let you say that we're really pleased not only with the launch in UC, but also, as you noted, where we are with MS. We're the #1 SP in terms of written scripts in MS. That's as expected. We've made great progress in terms of optimizing the patient pull-through to commercial dispense, and we are making very good progress at becoming the #1 SP in terms of commercial dispense. So we're very happy with the progress that we made on the MS side. With respect to UC, we're obviously excited to be launching in that space. We have a great team. This is a new area for us, and we've built an experienced home office and field team. Keep in mind, in terms of the size of that footprint, this is not a primary care market. We very much view this as a specialty market in terms of the size of the teams that we need and be successful here. But we've got a great team, and we see Zeposia playing a really more role in UC. And that's based on the impressive clinical profile that we have in terms of clinical and maintenance remission rates. We've got a clean safety profile here, obviously, in a convenient oral dose. And importantly, this is a novel mechanism of action within the IBD space. And we think, together, those factors are going to position us well to play with Zeposia in that prebiologic space. So right now, our focus is on educating customers with Zeposia and beginning to build volume. And building volume is going to be important here. As we've talked about previously. Access is a key factor to success. That's going to take some time to build that volume, but we've got a great team. We've got a great profile. And I think with the profile we've got, we've got a good story to tell.

Okay. Great. And on the access, maybe 2 questions. One, does that involve a sampling campaign? And then number two, does it help that you're already covered for multiple sclerosis? Or does that make it a little bit quicker? Or again, just it's going to take kind of the same typical amount of time that it usually takes to work through that formulary.

Yes. Samples and how you engage with patients from a patient support standpoint are typically offered in this space. What I would say with respect to MS versus UC access, they're distinct categories, and so I don't know that the our MS presence is going necessarily accelerating UC. I think what you're going to find in UC is that we're going to be able to build volume in those commercial lives that are in plans that are relatively open at launch. As we build that volume, we'll be able to engage with payers and negotiate with broader access. And that approach is one that's been done successfully by competitors, and it's something that we'll continue to execute on as we go through this launch. As I said, it's going to take time, but it's something that we're aided by having a great team and a very good profile.

Okay. Great. And I know one of the other indications that the clinical team is working on is Crohn's disease. Maybe Samit, you could give us an update on kind of how enrollment is going in that study, what have you guys said about time lines for data. And then remind us what gave you guys the confidence to move into that indication as maybe the next driver out of your growth.

Yes. So I think just as a background in the context of it, just like in UC, we have a Phase II study that supported the start of the Phase III studies. In a similar way, in Crohn's disease, we have the YELLOWSTONE Phase II study put from. And if you think about the totality of having the ulcerative colitis data and the YELLOWSTONE data, that led to the start of the ulcerative colitis study and the 2 Crohn's disease studies. And so the studies are enrolling well. But of course, we're impacted last year because, as Chris mentioned early on, when COVID, some of the indications were very hard hit and GI was one of them. And so certainly, we have recovered, and we are doing very well, and that enrollment has begun. In general, Crohn's disease studies take much longer or rather longer in terms of enrollment compared to the ulcerative colitis. And that's why we're looking forward to the data in the 2023 time frame of beyond. I think having the -- seeing the data for MS, having seen the data for UC, overall, having a new mechanism of action, the S1P modulators, bringing that into Crohn's disease is important because physicians and patients are looking for a new mechanism whenever they have to change therapies, and these patients do go through sequential therapies with various modalities. So it became very important, and we do believe it is important to pursue it. Having the positive trial in ulcerative colitis doesn't guarantee for Crohn's disease, but this does give us a little bit more confidence that patients and physicians will feel in terms of at least enrolling in the clinical trial. And hopefully, the readout is going to be passed, then we can take further.

Okay. Great. We'll stay tuned for that. The other important immunology asset on the pipeline side is your TYK2 inhibitor, which I can never pronounce the name. And so you had the Phase III data, 2 positive studies that you presented at AAD back in April. And so again, maybe just quick overview of the clinical profile versus your expectations. And I know you guys are probably working hard on the NDA right now. So what are the gating steps to getting that into the agency?

Yes. So we'll obviously share when the file is there and the validation we're going to get from a joint perspective. We are -- certainly, it's a priority for the company. We are very pleased with the data we have in hand. Certainly looking forward to the approval in the second half of 2022. But again, we have to collate the data. It 2 very large Phase III trials, along with all the supportive studies. And certainly, we, as a priority, are working towards finding that. There's no gating in terms of more data, et cetera. So it's just working through those, bringing them all together and having a good document that we can submit to the FDA so that the filing time and all those can move very diligently.

Okay. I guess the other corollary topic, I know you guys presented very detailed safety data. It looks like you're not seeing any of the JAK-like side effects, but I think this still remains somewhat of a question just given the regulatory review of the JAK class broadly. And so as we see these upcoming, whether it's a label update or regulatory decisions from the FDA, do you think there's any lateral implication for the TYK2 program as you think about a potential label, et cetera, on the forward? And when will you have more visibility there on that topic with respect to your conversations with the agency?

So I'll start off and then certainly, Chris, feel free to add to that. I think from what -- as a physician, what we hear from physicians as we talk to them as they've seen the data, especially after AD, we don't hear the same concern for a TYK2 inhibitor as that could be for a JAK inhibitor. So we have to keep that in mind from our overall profile of what we've seen with [ robustness ]. In terms of the safety aspects of it, the acute and the long term, we don't see that profile as a JAK inhibitor. We see it as a first-in-class TYK2, so very pleased with that. As we go through the motions of filing and then continued dialogue. Because, as is normal, FDA will always have the review team review the data, they will last questions, we'll give more analysis, we'll answer those questions. I don't think it's -- for me, I don't worry so much at this time about what label change is coming for the JAK2 inhibitor because that's not what we are. So that's -- what I worry about is we need to get the file in the hands of the agencies and then take it from there. But I'm sure that Chris would like to talk more about what he's hearing from the KOL side and how he sees in that as well.

Well, what I would say from a commercial standpoint is that, to a certain extent, while there's noise around the JAK inhibitors, I don't worry so much about that at all from a commercial standpoint. We have 2 Phase II -- Phase III studies that clearly show benefit relative to the existing standard of care. That benefit is clearly superior on efficacy. It's actually superior on safety as well. We've got a very convenient dose and formulation for this product. And so we think we are very well positioned against the current branded standard of care. And so we fully anticipate that we're going to be able to capitalize on that superior profile. We've built a very good team here. We continue to hire very experienced folks in the space. And so that's going to be our focus at launch. And again, I think we've got a good profile and a very good team to be successful here.

Okay. Great. And I guess, Chris, in the event that you were saddled with some of the black box warning language that's on the JAK inhibitors. I mean how does that change your commercial go-to-market strategy, if at all?

I don't think it changes anything at all. I mean, I think the reality is the physicians that we have been showing the TYK2 data going back to the Phase II are many of the same physicians who are weighing in on some of the discussions taking place around the JAK inhibitors, and what we hear consistent is that this is a superior profile relative to the existing branded agent for moderate-to-severe patients. And that based on this profile, this is going to be the preferred agent. So I don't worry so much about what happens with respect to how the FDA looks at this vis-à-vis the JAK inhibitors.

Okay. Okay. Great. All right. We'll stay tuned on the NDA filing and then ultimate PDUFA date next year. Again, another important launch product as you guys made a big push into the CAR-T space and you're launching 2 CAR-T products now. I think Abecma, you guys are the first year with the BCMA. And so a lot of focus on this launch. Maybe just, Chris, walk us through some of the key learnings from maybe the first wave of CAR-T launches. What do you guys think you can do to kind of capitalize on some of those learnings here? And as a result, should we expect that the Abecma launch might be somewhat better than what we saw from the first go-around with the CAR-Ts in lymphoma?

Sure. Well, what I would say is that we're very pleased with the launches of both Abecma and Breyanzi from a commercial standpoint. We have over 60 accounts that have been activated on both products. And remember, there's a high degree of overlap of sites across these products. For both products, we have patients that have been paid for recent treated, and we're seeing very good trends in terms of patient enrollment. And I think getting to your question about what are we seeing in terms of our ability to leverage not only the first-generation launches in cell therapy, but frankly, also our broader presence of having multiple cell therapy products in hematology. I think we've been able to benefit from that. The build-out of our customer infrastructure has been very good. We've seen, as I said, the site activation has gone very well, and we've been able to accelerate the time to that site activation for Abecma because of our experience with Breyanzi. So I think us having a larger footprint here is very important. And as we've said consistently, us having a broader footprint in hematology gives us the ability to be talking to the treaters of these patients and be able to facilitate referrals to the sites that are actually treating these patients. Many of the constraints that you saw with the first generation of cell therapy was around logistics. I think, by and large, the customers in these larger centers have worked through how to administer these products. There was obviously a concern around access. The access dynamics have improved considerably. And in fact, with respect to Breyanzi and Abecma, we've really seen no access concerns. So I think some of those early issues that were hiccups for the first generation of products really have not been at play here. And obviously, that's facilitated by what we think are very good profiles for both of these drugs. So our focus right now is really on optimizing these launches.

Okay. Okay. Great. Maybe just a follow-up on Abecma is -- and again, it's always hard to do these cross-trial comparisons. But coming out of ASH last year, ASCO this year, it does look like J&J Legend has maybe a higher CR rate. We're still waiting on longer-term follow-up on the PFS. But as you think about them using that as kind of a counter detail point to your CR rate with Abecma. What's kind of the counterpoint that you guys are going to make to your prescribers? Obviously, you have a depth of knowledge and relationships here in myeloma going back a long time via Celgene. So how do you kind of leverage that? And what's the counterpoint to that argument?

Well, the data from cell to cell certainly looks very interesting. And so we'll wait and see. Obviously, some of the things that you highlighted are yet to play out in terms of how they're labeled and when they launch. Based on the launch of Abecma, I think a few things are clear. First is a clear need for innovative therapies for these later-line multiple myeloma patients. These are patients who have very few of any additional options. As we discussed at the ASCO a couple of days ago, we're actually seeing considerable demand for Abecma. That demand is actually exceeding our current supply. We're obviously working to build that supply. But if anything, what we're seeing is that the demand suggests that there's room for multiple agents for these players. And at the end of the day, the innovation that we're seeing in these later-line spaces like multiple myeloma, relatively short period of time is good for patients. And so we continue to believe that Abecma is going to play an important role here. We do believe that being first has some advantages. Obviously, we're getting familiar with how to work with customers as to how to administer cell therapy for these specific patients. I already referenced the fact that us having a broader commercial infrastructure to support cell therapy is an advantage. So I don't discount the importance of those things as we face imminent competition. But at the end of the day, I think in this space, in particular, there's room for agents.

Okay. Great. And I think one of the other areas that physicians and patients are excited about is potential for these CAR-Ts to maybe move earlier in the paradigm. So Samit, maybe you could just remind us when we might start seeing some of that data from earlier lines of therapy as we think about the forward outlook as another potential growth driver.

Yes. So first, starting with Abecma. We have the studies ongoing right now for KarMMa-3, which is a third-line plus population. That study is in enrollment right now that -- because it's earlier line, we have a longer follow-up, so '23, '24 is when the readout is scheduled for bimonthly. And then we have a Phase II study that are enrolling earlier-line patients as well. KarMMa-4 is enrolling patients with high-risk first-line patients as well as KarMMa-2 also enrolling earlier-line patients. And later this year, we'd start enrollment with KarMMa-7, which looks at the combinations of Abecma plus the standard of care treatment. So those things will read out in '22, '23 and beyond as well. So -- but very excited to move these very effective therapies earlier in mind. I, obviously, do that context, though the fact that this morning, we also announced the earlier-line data for Breyanzi, which we are very excited to see the readout and looking forward to taking that also in lymphoma -- for lymphoma patients because these are game-changing therapies, and they are very important.

And I think we're seeing a lot of excitement from customers around Breyanzi and the question does continually come up when turning this into potentially earlier lines of therapy. And so the data this morning is obviously very important. We do believe Breyanzi has a best-in-class profile amongst the CD19 targeted agents. That's certainly playing out with respect to how we see the launch going in our existing indication. And so overall, I would say Breyanzi is off to a good start. I mean this was referenced by Samit. We've got additional opportunities to grow in the spring.

Great. Great. Maybe just 1 follow-up there, Chris, on Breyanzi. The outpatient dynamic, I know that's something else that you guys have focused on a lot. Are you seeing any early uptake there in that setting? Or is it more centers are first getting experience kind of an inpatient setting? And then this is something that's maybe more back half of the year into next year?

Yes. I mean right now, we're -- I think it's the latter of those things. I think right now, you're seeing that most of the use of these products, like for all of the use of the products is in the inpatient setting. We do believe that for Breyanzi-specific, because of the profile and the experience that we have with the clinical trials in the use of the product in an outpatient setting that eventually, we'll see some use in the outpatient setting. It's difficult to quantify exactly what that will look like. But for that product specifically, we think you may see a migration for some patients into the outpatient study. And that would obviously be very good for patients in terms of their ability to access these therapies.

Great. Okay. Great. I guess the other kind of corollary pipeline program is your T cell engager against BCMA. You guys have been working on this. And I just wanted to get maybe an update. Is this something where we can expect some more data at the ASH conference this year?

Yes. So if you recall from the IV part, we have very high response rates. But of course, there was the toxicity that was associated. We are right now enrolling patients in the subcutaneous formation program. I'm not so sure it will be at ASH or it will be next year. It will depend on the follow-up as well as the enrollment that we will have. So more to follow on that side right now. I can't say that it will be at ASH.

Okay. Okay. Great. I guess the other topic just on the heels of ASCO that I want to touch on a little bit is your LAG-3 program. Obviously, here, you're building on a rich history in terms of PD-1, CTLA-4 and now LAG-3 with another IO-IO combo here in melanoma specifically. Maybe just for Chris. First, as you think about the paradigm here, I know you guys have talked about kind of the 3 different buckets of patients in melanoma. Where is LAG-3 Opdivo going to fit? Or where will you position it from a commercial perspective as you think about growing that market on the forward once you have approval?

Yes. Well, obviously, the data is very exciting, and we're looking forward to being able to launch it. As you said, we do look at melanoma in sort of roughly 1/3. 1/3 of that is Opdivo + Yervoy. That share, as you know, Terence, has been remarkably stable over time, reflecting, I think, the well-established durable survival benefit we've seen with Opdivo + Yervoy. There's 1/3 of this market that is also IO monotherapy, and that's roughly split 50-50 between Opdivo and KEYTRUDA and then the final third is non-IO maybe TKIs. And you can think about that as really being targeted to the BRAF meeting patient population. As we've said, we think, at launch, the opportunity for [ rela-DIVO ]rela-DIVO is going to be to go after the IO monotherapy use. Given the benefit that we've seen in the study relative to OPDIVO monotherapy, which is all the high bar in melanoma, we think there's clear opportunity here. Now the ability to potentially expand beyond that is going to take a little bit of time. If you look at Opdivo + Yervoy, we're going to have to see longer-term follow-up data for [ rela-DIVO ]. Just get into the clear and profound long-term survival benefit you see with Opdivo Europe space. And then potentially, if you're getting more data, you may have an opportunity to go after [indiscernible], but we very much see the initial opportunity in that IO monotherapy. And then clearly, depending on data, we have opportunities outside them.

Yes. Okay. And then maybe 2 for Samit on the same topic. The first is, have you guys talk to regulators yet about the potential to file on PFS versus waiting for OS? And then the second question is, are you going to move into an adjuvant setting here with LAG-3 Opdivo?

So on the first question, progression-free survival is an accepted endpoint in first line. So we are then going to have that dialogue and can continue on. Of course, we are blinded to the overall survival data, overall sponsor data, we'll provide when available to regulators. And obviously, we'll be presented that in the [ conference ]. For the second part, just remind me...

Adjuvant, potential for adjuvant.

Yes, of course. And as we've said, yes, later this year, we'll be starting the adjuvant trial, not only just looking at the melanoma setting, but we have the ongoing program in first-line setting for non-small cell lung cancer and then also hepatocellular carcinoma. The non-small cell lung cancer program is just looking at the safety of combining NIVO plus LAG-3 plus chemotherapy. And then once the safety has been elected, then we could launch the Phase III program in the first-line setting for that combinations.

Okay. And how strong is that preclinical data for LAG-3 and melanoma relative to HCC in lung? Is it about the same? Or is it maybe there's any differences you'd want to call out?

I think the way we look at it is that we've got the Phase Ib/II studies that we did conduct early on looking at NIVO rela, and we did see signals of activity over there. What we have learned also from the general NIVO + IPI programs with chemotherapy, we've seen what NIVO + IPI does and what NIVO + IPI and chemo does in terms of changing the shape of that current in the early part of the capital [ matter ]. Looking at the overall profile of NIVO rela, combining it with the early data that we saw in lung cancer, we chose to go into the Phase II program so that we can define the safety and collect partly efficacy data. We have not conducted a randomized study trial. And therefore, it is important to collect the contribution of components part as well. That's why the Phase II study is NIVO, rela, chemo versus more NIVO, chemo. So that we can answer that 1 question on what does rela bring. And then in the Phase III, we'll compare it to the standard of care so that we can get the registration done. So early data is very promising. That's why we've gone [indiscernible].

Okay. And when would we -- when might we see some of that lung data? Is that a this year event? Or is that more likely 2022?

More likely a 2022 then because, as I said, we just started the program, so we need to follow up and gather the data as we go towards the Phase II.

Okay. Okay. Great. Maybe just in the last couple of minutes here, back to Chris. On Reblozyl, this is another important product launch for you guys. Again, you have a big established presence already in this market. But maybe just give us an update on what you're seeing in terms of the recovery trends here, new diagnoses, et cetera, in the U.S.

Sure. Well, we're pleased with how things are going with our Reblozyl. Generally, the feedback on the product has been very good. We've seen a nice pickup in execution, particularly as we've begun to get in and see more customers in recent months face-to-face because we have seen an improvement in our ability to engage with customers that reserve. This was another market that was heavily constrained in that regard. We have seen some pickup in new patient volume as well in MDS generally, and that's translating into the market that we have with our existing approval. So this is another product where we continue to see significant opportunity to grow this product over time. As we said in the first quarter call, we've seen a bit of a prolonged bolus washout period for this brand. We estimate about 25% of the business is comprised of these early bolus patients. But those patients are going to wash out over the course of the next quarter or so. And then we expect to see more pronounced growth as we get into the latter half of the year. But the fundamentals on this brand continue to support significant growth.

Okay. Great. And then sorry, last minute, I just got an e-mail question for Samit on the follow-up on the LAG-3 lung cancer study. What's the chemo dosing in that study? Is it continuous? Or is it a fixed chemo regimen?

Meaning number of cycles you mean to say, 2 cycles?

Yes. Yes.

It's 4 cycles, if I remember correctly, but I have to correct myself, I have to go back and take a look.

Okay. Okay. All right, guys. Well, I think we're up against time, but really appreciate the insights today. Thank you so much for taking time out of your day and stay safe.

Thank you, Terence. Bye-bye.

Thank you, Terence.

Thank you. Bye.

Bye-bye.