Good day and welcome to the Bristol-Myers Squibb 2022 Second Quarter Results Conference Call. Today's conference is being recorded. At this time, I would like to turn the call over to Mr. Tim Power, Vice President, Investor Relations. Please go ahead, sir.

Thanks Sara and good morning everyone. Thanks for joining us this morning for our second quarter 2021 earnings call. I'm joined this morning with prepared remarks by Giovanni Caforio, our Board Chair and Chief Executive Officer; and by David Elkins, our Chief Financial Officer. And also part in today's call are Chris Boerner, our Chief Commercialization Officer; and Samit Hirawat, our Chief Medical Officer and Head of Global Drug Development. You'll note that we posted slides to bms.com that you can use to follow along with for Giovanni and David's remarks. Before we get started, I'll read our forward-looking statement. During this call, we'll make statements about the company's future plans and prospects that constitute forward-looking statements. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the company's SEC filings. These forward-looking statements represent our estimates as of today and should not be relied upon as representing our estimates as of any future date. We specifically disclaim any obligation to update forward-looking statements, even if our estimates change. We'll also focus our comments on our non-GAAP financial measures, which are adjusted to exclude certain specified items. Reconciliations of certain non-GAAP financial measures to the most comparable GAAP measures are available on bms.com. And I'll hand it over now to Giovanni.

Thank you, Tim and good morning everyone. Let's start with our second quarter performance on slide four. We are midway through 2022 and we've made great progress during an important year for the company. We continued to grow our in-line franchises, expand our new product portfolio, advance our pipeline, and execute important business development activities. Our foundation is strong and positions us well for growth. With respect to our commercial performance, we delivered continued sales growth with revenue up 5%, adjusting for foreign exchange and non-GAAP EPS increasing by 18%. The strong revenue growth was driven by excellent commercial execution with solid year-over-year growth for our in-line brands, particularly for Eliquis and our I-O franchise and significant momentum from our new product portfolio. Within our new product portfolio, Opdualag, our third I-O agent is off to a great start, and we are pleased with the team's early execution. Opdualag strengthens our position in I-O and accelerates the sustainability and growth of our I-O franchise. We are also establishing a strong foundation for Camzyos. As the first agent that effectively treats the underlying condition of symptomatic obstructive HCM, we see a lot of potential to drive significant penetration in this large underserved and underdiagnosed population. We also made great progress advancing our broad set of pipeline opportunities through regulatory approvals and clinical trial readouts during the quarter. In hematology, we received US FDA approval for Breyanzi with a best-in-class label in second-line large B-cell lymphoma as well as EMA validation. With this approval, Breyanzi now has the broadest patient eligibility of any CAR T cell therapy in relapsed or refractory LBCL. This reinforces our opportunity for leadership in cell therapy and further strengthens our view of Breyanzi as a key growth driver for the company with over $3 billion in non-risk-adjusted…

Thank you, Giovanni, and thanks, again, for all of you joining our second quarter earnings call. Let's turn to Slide 8 to discuss our solid top line performance. Unless otherwise stated, I will discuss our sales performance growth rates on an underlying basis, which excludes the impact of foreign exchange. Second quarter revenues were approximately $11.9 billion, growing 5% year-over-year. This performance was driven by robust growth of our in-line and new product portfolio of 16%, more than offsetting our recent LOEs. Let's now double-click on our new product portfolio performance on Slide 9. Global revenues were nearly $500 million, more than doubling revenue versus prior year. Growth over prior quarter was also very strong, up 38%, primarily due to strong launches of Abecma and Opdualag, which I will touch on in a moment. I'm very pleased with the performance of our new product portfolio and its future potential with two additional launches year-to-date and Deucravacitinib anticipated approval in six weeks. Our new product portfolio has significant expansion opportunities and the potential to generate greater than $25 billion in revenue on a non-risk-adjusted basis in 2029. I look forward to updating you on these products as they continue to realize their full potential. The performance of our solid tumor portfolio, shown on Slide 10 was strong. Opdivo sales in the quarter continued to grow globally, driven by demand for our newly launched and core indications. In the US, we delivered 12% growth for Opdivo versus prior year, driven by demand in first-line lung, renal and gastric cancer, as well as adjuvant esophageal and bladder cancers, partially offset by some – by Opdualag in first-line melanoma. Internationally, revenues were also strong, growing 13% primarily due to growth from new indications, particularly first-line lung and renal cancers. As we continue to secure…

Thanks, David. Sarah, could we go to our first question, please?

Thank you And we'll take our first caller from Chris Shibutani with Goldman Sachs.

Hi. This is Dan on for Chris. Thanks for taking our question. Two from us. First on the Milvexian readout, if you could maybe frame some areas of focus into the ESC data and provide any additional color into how you're thinking about the Phase 3 program as the data is in-house. And then second, on Camzyos, if there's any additional feedback you can provide on some of the early launch dynamics and your expectations into the second half of the year and early next year. Thank you.

Thank you, Dan. Samit will answer your question on Milvexian, and Chris provide some incremental color on Camzyos. Thanks.

Sure. Thank you, Giovanni, and thank you, Dan, for the question Milvexian, certainly looking forward to having the data presented at ESC and discussing the results. And of course, as you know, we'll go into the details with the other specifics of the data itself. But I think there are two questions that probably are important to answer, than we look at the data. And that would be one related to the efficacy, specifically when it comes to impact on clinically proven ischemic strokes. And the second, of course, is to look at bleeding rates, and more specifically over there, one that physicians and patients would be interested to know about would be probably related to intracranial bleeds, where patients with strokes have a propensity to have the – as well as if there are any further bleeds. And so those are the kinds of questions that we set out to answer. And I think those are the questions that people will be very interested to know. For Camzyos, let me pass it on to Chris to take you through.

Thanks, Samit, and thanks, Dan, for the question. We are very pleased with the early launch of Camzyos, while it's still very early days. We're off to a very good start. And what I would say is that, by and large, the performance that we're seeing is aligned to our expectations. And I would highlight maybe two or three things. First, awareness is very good. We've seen incredibly strong enthusiasm for the product from both physicians and patients. Importantly, the feedback that we're getting on the clinical program has been overwhelmingly positive and consistent. I'm going to give you some vignette on that. Patients are seeing significant benefit, both in terms of feel and function. And that benefit is being seen very early, in fact, as early as four weeks post initiating treatment. And that's really important because it's driven a lot of enthusiasm, both from patients and its given physicians, a reason to believe that the product is living up to the promise that we have. In terms of physician experience, the feedback has been very positive. The REMS education that we've initiated is intuitive, getting on and certified for REMS has been straightforward. And as David mentioned, that's translated to over 1,400 HCPs being REM certified. And one thing I would highlight is that this is probably the most important leading indicator for this product launch, given the fact that you don't have a history of REMS in the cardiovascular space, physicians are going to be REMS certified if they have intent to use. The last thing I would highlight is we're seeing a healthy increase in the number of centers prescribing week-over-week. We don't see any access issues on the horizon that would prevent these patients who are getting on to therapy converting to drug. And so if I sum it up, performance is in line with expectations. We're happy with what we're seeing, and we very much look forward to the continued uptake of this product over the course of the year.

Okay. Thanks, Chris. Sarah, can we go to the next question, please?

Thank you. And next, we'll take Andrew Baum with Citi.

Thank you. First question on Milvexian. Is there any possibility you could expedite what's going to be a very large and long duration clinical trial program through the adoption of MRI-defined strokes within a composite end point either to expedite the trial or to decrease then acquired for the trials? Second, could you comment on whether you are exploring your CD19, CD3 at your CD19 CAR T, excuse me, Breyanzi, for autoimmune indications given some of the recent data in lupus. And then finally, one of your competitors announced some intriguing data with the related to in MSS colorectal cancer. I know that Bristol has one in, I think, two, if you could provide us any update on that, that would be useful. Many thanks.

Thank you, Andrew. I'll ask Samit to answer your three questions.

Yes. Thank you, Giovanni, and thank you, Andrew. Very thoughtful questions, as always. For Milvexian, look, we're not obviously going to get into the Phase 3 indications right now. But from a Phase 2 perspective, you will certainly get to see the data. And what is important is from a physician's perspective, what matters really is the clinical strokes and those certainly will be the questions to discuss when the data are presented. On the CD19 side, certainly very intriguing data in the autoimmune disease, especially in the lupus, SLE patients who are severely impacted by the disease. Those are the things that we continue to discuss from a scientific perspective, how to explore, where to explore and certainly not hitting from us. And as we evolve in our thinking, we'll share with everyone where we are going with that, the German data were very intriguing, I have to say, and as we presented earlier this year. For CTLA-4, we've seen the data on CRC from a competitor. From our perspective, we have three CTLA-4 antibodies in development, the Non-Fucosylated Probody as well as the Non-Fucosylated Probody. So there are three that are in development. The way we think about it is, number one, we have an ongoing study in MSS TRC for that you know that we just initiated the Opdualag comparing to the standard of care. And for future developments for CTLA-4 antibodies, we have to think about combination strategies because we know that many times even in the past, when single agents have been used, the response rates ultimately in registration trials have really been single-digit or low single-digits in fact. So we will obviously be able to share the data once we have these combination studies completed. They are currently ongoing. Too early to talk about the data at this time. We're certainly aware of the CRC data.

Thank you, Samit.

Sarah, can we go to the next question, please?

We'll take our next question from Geoff Meacham with Bank of America.

Hey, guys. Thanks so much for the questions. I had a commercial one and a pipeline one. Chris, on Reblozyl, can you talk about the US trends, what does duration of therapy look like today versus, say, a year ago? And does demand support upside your peak forecast? And then Samit or Giovanni, I know Turning Point hasn't closed yet, but how much of a focus is I-O plus targeted therapy for Bristol looking forward? I know you ROS1 combos are probably more likely than not to come -- to play out in the pipeline. But beyond that, do you guys see this as sort of a new type of modality to sort of bolt-on to an I-O strategy? Thank you.

Thank you, Geoff. Chris, why don't you start on Reblozyl and then Samit will comment on oncology strategy.

Yes. Thanks for the question, Geoff. We're very pleased with the continued uptick that we're seeing with Reblozyl. We had good growth in the quarter versus prior year as well as sequentially. I would highlight a few things. First, we're continuing to see good acquisition of new patients for this product. One of the things that we look very carefully at is what are physicians' perceptions of the product and importantly, how quickly they're moving patients off of ESAs to get on Reblozyl therapy. That time on ESAs when patients are not getting an adequate response continues to shorten, which is a leading indicator of the number of patients that will be within the indication that we have. And importantly, we're seeing nice trends in both dosing and administration. The average MDS dose by cycle has grown steadily during the course of this launch and has increased this year. That's resulted in improved efficacy and longer duration of therapy which, to your question, has been up 6% this year relative to where we were in 2021. And while your question was mainly focused, I think, on the US, I would highlight that ex-U.S., the launch is early, but we're seeing very good uptake in the early launch markets, notably markets like Germany, and then we'll have additional access and reimbursement decisions ex-U.S. So overall, we feel very good about where we are, and we look forward to continued uptick of this product as we go through the remainder of the year.

Thanks, Chris and Geoff, maybe I can take on the Turning Point question. So first of all, excited about the acquisition of Turning Point Therapeutics and looking forward to bringing repotrectinib to patients in the second half of next year. Your question around the combinations. Those are all going to be always data-dependent and so explorations will continue. Although at this time, certainly, there is a lot of knowledge and lots of emergence of data TKI combinations or tyrosine kinase inhibitors, which are not necessarily mutation-specific tyrosine kinase, which have generated a lot of interest and a lot of data and have been approved in multiple indications when combined with I-O therapies, but it does provide additional opportunities in the future to look at these sorts of combinations and more specific pre-specified populations and selected patient populations, but those will be data that will need to be generated at the current time, too early to tell.

Thank you, Samit.

Great. Sarah, can we go to the next question, please?

We'll take our next question from Chris Schott with JPMorgan.

Hi, great. Thanks so much for the questions. I guess the first one for me was on Breyanzi in terms of what's the latest on maybe the timing and maybe as importantly, the magnitude of your capacity expansion. It sounds like this might have been getting pushed out into 2023 versus I think previously, you were talking about maybe a 4Q target. I just wanted to elaborate a bit more on what's happening there? And the second question was on Camzyos. I know there's a bit of a lag between when docs get certified for the REMS and when Bristol actually starts to generate sales for the drug. But as we just kind of think about the sales ramp from here, should we be thinking about this as a fairly gradual process, or is this a product that could see a steeper ramp starting sometime later this year, given the third some identified kind of patients out there? I'm just trying to see in terms of expectation setting of how to think about the ramp given some of the, I guess, the promising initial data in terms of the number of physicians getting certified, et cetera. Thank you.

Thank you, Chris. Chris .

Thanks for the question, Chris. On Breyanzi, what I would say just at the outset around cell therapy in general, is that the demand in the quarter for both of these products, Abecma and Breyanzi, was strong. We continue to be very pleased with the feedback on the profiles of these products and importantly, how those profiles position us competitively. With respect to Breyanzi, as David mentioned earlier, we had underlying demand that was very strong. We're obviously very pleased with the second-line approval and the fact that it's given us the broadest label of any CAR T in DLBCL. But as David also mentioned, sales were impacted in the quarter by manufacturing success rates. Those success rates, the issue underlying that was resolved, and we expect success rates to improve as we head into this quarter. More generally around manufacturing with Breyanzi, given the broader label, we had obviously hoped to have increased capacity in the second half of this year. We're now anticipating that in Q1 of 2023, delivering that capacity is a top priority. The focus here is on increasing both vector and drug product supply. I will note that we've seen a nice increase in the capacity for Abecma, driven by successful drug product expansion and increasing in vector supply, and we anticipate that, that same focus will be now applied to Breyanzi and have every expectation that we'll be able to deliver on that. That capacity is going to be important. Because given the broad label with this product and the compelling profile, slot availability is going to be critical. So the good news is we have a very strong manufacturing team focused on increasing the supply, and we look forward to delivering that supply in the first part of the year. As for Camzyos…

Thanks, Chris. Sarah, can we go to the next question, please?

Thank you. We'll take our next call from Steve Scala with Cowen.

Well, thank you very much. A couple for Samit. First, in your deucravacitinib FDA discussions to date, has there been any mention of a box warning whatsoever, or has that not come up in any conversation? And also given the time frame involved, can we assume there won't be an ADCOM? And then the second question is based on available data, does Bristol think other cardiac myosin inhibitors will have black box warning, or do you think they could avoid that? Thank you.

Thank you, Steve. Before I ask Samit to answer both of your say, as you know, we don't comment on ongoing discussion with regulatory authorities, but Samit will provide his perspective on both. Samit?

Yes. Thank you. Steve, as Giovanni has mentioned, no specifics to be provided here. What I can repeat, I think, from the past conversations we've had is our confidence in the data itself and we think about from an efficacy perspective, differentiation and superiority that has been proven through the Phase 3 trial versus Otezla from a safety perspective, showing differentiation when we think about the JAK inhibitors versus deucravacitinib, first in inhibitor. And this is that profile that has continued to evolve through multiple other trials that has given us the confidence to initiate the programs, as you know, in psoriatic arthritis, two Phase 3 trials ongoing, and also now looking forward to initiation of the SLE Phase 3 trials at the end of the year, beginning of next year. So overall, we're looking forward to September 10 PDUFA date and bringing this new medicine to patients. In a similar way, I would say, in the cardiac myosin inhibitors, it is difficult and not appropriate probably for us to comment on other people's drug as to what a profile is going to look like and if they will have any warning and precautions in the label or not. What we can say though is again I believe in Camzyos as already alluded to buy by Chris well and David his remarks are our believe in the data and our physicians are acting in terms of getting trained and prescribing it to the patients. So overall, looking forward to the initiation of our non-obstructive Hypertrophic Cardiomyopathy Phase 3 program towards the end of the year. Thank you.

Sarah, can we go to the next question, please?

Yes. We'll go on to Seamus Fernandez with Guggenheim.

Thanks for the question. So just a couple of quick questions. First off, this is really for Giovanni. Should Congress pass the Medicare pricing reform. Can you just help us understand what impacts you think this is likely to have, whether it be on innovation but also on your own long-term guidance from that perspective. And are you hopeful that there might be -- should this go through potential changes that could temper the impact perhaps a push out of this small molecule of nine years of protection and perhaps maybe push that out to 12 or 13 years. Just wondering if there's -- there are any opportunities to think a little bit more constructively about this. And then separately, hoping to just get a little bit of color on the launch dynamics around deucravacitinib. You guys are commenting on your enthusiasm to kind of get this product to market and to patients. Just wanted to get a better sense of should the label actually have a JAK boxed warning, which we don't necessarily anticipate, but should that occur, what are you hearing from physicians with regard to the opportunity to kind of work around that? Maybe just as a clarifying question. We've gotten a lot of questions from investors on the possibility that if there were a JAK warning, could it actually be post biologic, doesn't make a lot of sense to us. Just wondering where you guys stand on that proposal. Thanks so much.

Thank you, Seamus. Let me start on pricing reform and then Chris will comment on deucravacitinib. So first of all, as you know, discussions are ongoing in Congress, and it's difficult to speculate exactly on the bill and some of the details. They will be included in the bill. There will also be obviously a long period during which implementation of some of the measures will be clarified and some of the dynamics would be really important to understand. So with respect to your question on would there be an impact to innovation. So first of all, we've consistently said that the elements of reform that improve affordability for patients, we are supportive of. And so as an example, the redesign of the Part D benefit and establishing another pocket for patients. That's very beneficial, and we are definitely very supportive of that. There are elements in the bill, however, which are obviously very detrimental to innovation and particularly price setting by the government at nine and 13 years, obviously have the potential to have a negative impact on innovation overall. I would say that with respect to the impact for our company, there's two things I can say at this point. First of all, it's really not helpful to look at our exposure to the channel today. I think it's important to really understand the dynamics that will develop over the next few years before these policies are implemented. And a couple of things I'd like to say. First of all, obviously, as you know, Revlimid revenues in the US are declining rapidly. Eliquis, we share that 50% with Pfizer. And then importantly, as you think about Opdivo, that loses exclusivity at the end of the decade. So what I can say is that our rapidly diversifying portfolio and a significant number of new medicines that we're launching today and would be launching before some key elements of this policy are implemented, position us well to navigate the challenges associated with reform for the entire industry. But obviously, there is much more than we need to learn, first of all, through a potential finalization of the bill; and second, really understanding better some of the elements of its implementation.

So maybe I'll pick up, Seamus, on the question regarding deucravacitinib and the launch. So where, as you know, very excited about the opportunity to launch this product. As was referenced previously, the commercial and medical teams are in place. They're ready to go. They're very experienced. What I've said previously, I think, is where we'll start this conversation, which is that we explore every meaningful scenario as we think about the launch of any new product, but we continue to index heavily on the scenario, where we think that the preclinical and clinical data support and that is that this is a unique mechanism of action that is clearly differentiated from other products in the class. And actually, when we talk to customers, we get an almost uniform alignment that, that's the right way to think about deucravacitinib, that the mechanism based on all of the data that we've seen is unique and it is differentiated, it's differentiated not only from JAKs, but it's differentiated, most importantly, from the current standard of care for oral agents treating moderate-to-severe patients. And so as we step back and think about this product, we anticipate very strong demand for deucravacitinib based on the clinical profile from 2 Phase 3 studies that show clear superiority relative to the existing standard of care. We have a unique mechanism of action that's clearly differentiated and we think positions us well to become the oral branded of choice for these moderate-to-severe psoriasis patients. And as was implied in the premise of your question, we're very excited to launch this product, and we look forward to the PDUFA date in September.

Thank you, Chris. Sarah, could we go to our next question, please?

We will take Luisa Hector with Berenberg.

Hello. Thank you for taking my question. You showed your slide on business development, highlighting the importance there. I just wanted to check, has there been any shift in the activity, the trends in companies coming to you versus you approaching other companies? Just any more recent trends given the longer duration now of depressed valuations, just whether you're seeing any shift in those dialogues that you're having with Target. Thank you.

Thanks, Luisa. I would say nothing has changed there, continues to be an area of great focus for us. We're looking at bringing new science into the company. You are right, the valuations are resetting now for a longer period of time, and we plan on continuing to be very active in this field. It's always been a priority for us.

Thanks, Giovanni. Can we go to the next question, please?

Thank you. We move on to Tim Anderson with Wolfe Research.

Hi. I have a question on Milvexian, which is historically, when companies have added together anti-platelet therapies or anticoagulant therapies to try to achieve better results, it pretty much always results in higher bleeding and that calculation is whether that higher bleeding is more than offset by higher efficacy. So in SSP setting, just theoretically ignoring any data you already have at hand, shouldn't we expect that same sort of thing where we would likely see at least some additional bleeding and then we'd have to wait against efficacy, or is it in the realm of possibilities that you really don't see any additional bleeding in that triple therapy arm? And then TYK2, you guys expressed high confidence in the molecule. I'm wondering why you haven't advanced yet to mild-to-moderate patients, if you're fairly confident in the label why not push ahead in Phase 3 and start to expand the market like Otezla has already done.

Thank you, Tim. Let me just ask Samit to answer your question, both on Milvexian and also plans for deucravacitinib.

Yes. Thank you. And certainly looking forward to, again, the presentation of the Milvexian data. I obviously cannot get into specifics of the data itself. But let me just reiterate that to two questions that would be important from everybody's perspective is on the efficacy, looking at the clinical strokes; and secondly, from a bleed perspective, it becomes very important, what kind of bleed and especially, when we think about the fatal bleeds, meaningful bleed that become important. If you look at the past, what you will see is those kinds of things that made people a little bit worried. So again, we can discuss more when we have the data presented at ESC around Milvexian. On TYK2, certainly, we are very pleased with the profile for the oral TYK2 inhibitor that has obviously evolved and continues to evolve in multiple other indications as well. As we look to the mild-to-moderate psoriasis, as we've said before, we are looking to bring in the topical formulation, the Phase 2 trials that are about to begin from the Phase 2 or from the TYK2 perspective, and that's our foray into the mild-to-moderate psoriasis. As you know, the pivotal trial was conducted in a moderate-to-severe plaque psoriasis patients. And then, of course, multiple Phase 3 trials in various indications. First of all, in psoriatic arthritis that are ongoing and then lead starting later this year and Phase 2 trials are ongoing UC as well as in disease. Thank you.

Thanks, Samit. Can we go to the next one, please Sarah?

Thank you. We'll move on to Evan Seigerman with BMO.

Hi, guys. Thank you so much for taking my question. I want to talk on the kind of dynamics between Opdivo and Opdualag. Can you provide more color as to the split between patients who are switched from Opdivo to Opdualag? And then one on Turning Point. I know kind of the when you announced the deal, it was still kind of TBD on the pre-NDA discussions with FDA, any update on the – on that may be will give us more confidence that you're able to launch in the second half of next year. Thank you.

Thanks, Evan. Let me just answer quickly your question on Turning Point, before Chris addresses your Opdualag question. So as you know, we continue to operate as two separate companies, at the same time as we've mentioned before, first of all, we remain confident in the ability to close in the third quarter of this year. And we're still looking at the launch of repo in the second half of next year. So all good there. Chris?

Sure. So we're very pleased with where we are with the Opdualag approval and the early uptake, the execution of the team has been very strong and physician reaction has been quite positive. In terms of the dynamics within the market, shares in first-line metastatic melanoma are in the low doubl-digits for Opdualag. We have seen some early use in second-line plus patients that's mainly driven by the fact that, remember, the flow of newly diagnosed metastatic melanoma can be somewhat staggered just given the volume of patients you have in this market. And so what we're seeing is not only are physicians using the product in first-line, but they're also looking to use it in second-line as patients either progress or they're willing to switch patients. In terms of who those patients are, that dynamic is playing out largely as expected. We're mostly displacing PD-1 monotherapy, that's to be expected, just given the strength of the clinical data with a more than 2x improvement in PFS and a strong trend towards overall survival relative to PD-1 monotherapy. We are seeing some modest conversion of Opdivo, Yervoy to Opdualag. But at this point, that's very much within the -- what we had expected. So overall, I would say Opdualag first, the performance continues to be very good. It's early days, but certainly, we have strong momentum. And the interplay between dual I-O, single-agent I-O and Opdualag is largely as expected.

Can we go to the next question, please Sarah?

Thank you. We'll take our next question from Terence Flynn with Morgan Stanley.

Hi. Thanks for taking the question. Maybe Samit, as we think ahead to Milvexian and the various Phase 3 opportunities, would just welcome your perspective on why Xarelto COMPASS data didn't really change the treatment paradigm in patients with CAD/PAD. Again, I know you're not going to comment in terms of where you're going right now in terms of Phase 3 opportunities, but just trying to think about risk, benefit in some of these other populations where Eliquis hasn't really found much usage. Thank you.

Thank you, Terence. Samit?

Yes. Look, again, Milvexian is a Factor XI inhibitor and the first of its kind, certainly, there are others that are in development as well. So looking forward to the presentation of the data and then discussing the Phase 3 plans, which will be towards the end of this year, the initiation, as Giovanni mentioned in his comments early on. I obviously cannot comment on why Xarelto, but certainly, Eliquis with this indication, you've heard Chris and David mentioned early on as to what has been accomplished with Eliquis and continues to accomplish, very effective treatment, we are trying to solve the Factor XIa inhibitors, some of the shortcomings that have been left behind core from the Factor Xa inhibitors and especially -- and from the Phase 2 trial, we're looking at also the combination of it with dual anti-platelet therapies. So that's the overall intent for the future development to look at multiple other opportunities in the ordeal as well as on the side from Milvexian as a single agent as well as in the combination with the background therapy. So more to follow. And certainly, after the data presentation, we can have a wide dialogue on the indications and the plans. Thank you.

Thanks, Samit. Sarah, can we go to the next question, please?

We'll take our next caller from Matthew Phipps with William Blair.

Hi, thanks for taking my questions. Another melanoma landscape question. The results of were presented at the recent ASCO showing Opdivo maybe should be used even ahead of BRAF inhibitor combinations. Do you think that's enough to drive more uptake of Opdivo and Yervoy in that setting in the front line, or is this thing you're going to explore with additional trials, maybe newer CTLA-4 antibodies?

Chris?

Sure. Well, thanks for the question, Matthew. We have long believed that I-O has promised in improving the outcome of BRAF mutant positive patients. Today, as you may know, the use of I-O, particularly as a first-line treatment in that population is still somewhat limited. It's around 30% to 35% of that population. The data that were presented actually last year at ASCO are potentially practice forming in that they provide, I think, important insights into how to best sequence dual I-O therapy relative to targeted therapy. And in particular, they show that the use of dual I-O before targeted CAFMAC therapy led to a significant improvement in -- to your overall survival. So in that regard, the data are compelling and it can inform practice. The one big caveat to keep in mind here is that targeted therapy combination used for first-line BRAF-mutant patients has been very sticky. And so while we may see some use of dual I-O in the frontline setting based on Dreamsic I would anticipate that would be mainly an academic setting, primarily because that's where the data are going to be most known. Remember, we can't promote to this data. So I think it's unlikely you're going to see broader adoption. That said, it's encouraging data, and it could have an impact on selected customers.

Thanks, Chris. Sarah, can we go to the next question, please?

Thank you. We'll move on next to Carter Gould with Barclays.

Great. Good morning. Thanks for taking the questions. I wanted to go to Eliquis and exactly kind of what's -- which countries are baked into sort of the second half headwind. You mentioned the $250 million headwind on the quarter. You made some intra-quarter comments. And we've seen some additional countries have generics like Canada. And I guess, just bigger picture, is it more appropriate to still think about Eliquis as a tailwind to overall company growth in 2023, given some of these headwinds, it seems like every month, there's a new country sort of launching generics. And I guess then secondly, just on deucravacitinib, how are you guys thinking about those IBD indications right now and specifically sort of the viability of those higher doses and if anything is shifted based on your conversations with FDA around psoriasis.

Thank you. Let me just start on Eliquis and then David will provide some more insight and Chris answer your second question. So what's referred to by David in terms of the impact of EU generics for the rest of the year at this point is the UK and the Netherlands. So let me just step back and remind you where we are in the UK, as you know, the high courts have found our composition to be invalid. And obviously, we strongly disagree with that ruling because that's the same patent that was actually upheld and reaffirmed in both the US and Canada last year, and we're seeking permission to appeal. The Netherlands is very different because in the Netherlands generic company decided to launch before the trial actually took place on the merits. And obviously, that trial is still ongoing. There are generics of Eliquis that we expect to enter the market in Canada that was planned later this year. And as we've communicated before, there are similar lawsuits ongoing in other in other EU countries and every country actually is completely independent and each jurisdiction will make a decision independent. From our perspective, we continue to be very much convinced about the strength of our IP and will defend every case in every country. David?

And Carter, also just recall, the vast majority of our growth comes from the US, and we have patent protection until April 1, 2028. So feel really strong about the growth potential -- continued growth potential of Eliquis by that. But just to contextualize our business in the UK is about $500 million. And what we said is it will be about -- between the UK and the Netherlands, it will be about $250 million this year. And as Giovanni talked about in the other European markets, we'll continue to vigorously defend our intellectual property in there. That provides some context on how we're thinking about the growth potential of this.

And then maybe I'll just say something very briefly on IBD and turn it over to Samit to talk about the development. IBD is obviously a large and underserved market. Some elements are more competitive than others, but in general, there's still a need for multiple oral options here. And given the profile that we've seen with deucrava, certainly through the psoriasis program, I think from a commercial standpoint, there would certainly be an intriguing opportunity for us, but Samit can speak more directly to the clinical plans.

Yes. So just to keep it very brief, that both trials are ongoing in Phase 2 right now, one in Crohn's disease, one in ulcerative colitis. And based on data, we will be making decisions on development as well as the doses. But I would say it has no bearing at all in terms of the approvability of the deucravacitinib in September for the psoriasis program. So rest assuring that. Thank you.

Sarah, can we go to the next question, please?

Thank you. We'll move on next to Dane Leone with Raymond James.

Hi, thank you for taking my questions. Two strategy ones for me, and this is something that comes up in almost every investor conversation. For you guys to win with Milvexian, the view is that you really have to have that head-to-head comparative trial versus riva in AFib, and AFib is going to represent the majority of the addressable market for Milvexian. And so the question is, from a lot of people's perspective, from a time line, it seems like you guys might be behind on that front. Could you just maybe address what your strategy is to get into AFib, what you view as the time lines for success. And then generally, how you view head-to-head trials is potentially mitigating the LOE associated with Eliquis as we go through this decade. And then kind of to the same point, there's a lot of questions of how you preserve the Opdivo revenues going forward and how much you can actually swap out with further studies of Opdualag ? And you have a number of ongoing but what do you really see as the potential of Opdualag peak sales from what you know now between what's going to cannibalize Opdivo and potentially Yervoy versus where are going to be de novo markets for pure growth. Thank you.

Thank you. Let me just answer your Opdualag question, first, and then Samit is best positioned to comment on Milvexian. So on Opdualag, as we've stated before, we see great potential for Opdualag. And as you look at and in fact we've articulated our perspective that peak sales for the asset can be from a non-risk-adjusted basis above $4 billion in revenue, and that, of course, comes from a number of indications. And when you look at the indications that we are currently studying, of course, melanoma is the entry for Opdualag, but there are trials ongoing in colorectal cancer, liver cancer and lung cancer. And in some cases, those are indications where we currently have a presence with Opdivo, in some cases, there are new indications. You are right when we look at Opdualag as an opportunity to provide durability to our I-O franchise And assuming continued successful development, there is clearly a potential for Opdualag to be playing in a meaningful part of the current revenue space for Opdualag. With respect to Milvexian, again, Samit will comment. Let me just remind you that as he said before, we'll be able to provide much more insights into develop the development program once you've seen that we presented the data. And obviously, we're looking at a broad set of indications well beyond AFib. But Samit?

Good. Just very briefly, thank you, Giovanni. What I would say that there will be data presentation, both from the competitor molecule and ourselves at the same time at ESC, neither of the two companies have started the Phase 3 program, and our partners, Janssen and BMS. We are, of course, looking forward to initiation of that program later this year. As I said earlier, both on the venous arterial side of things, single-agent combinations, and then we'll be able to talk about the competitors as well. So thank you.

Thanks, Samit. Sarah, can we go to the next one please.

Thank you. We'll move on to Colin Bristow with UBS.

Hey, good morning and congrats on the quarter. On mezigdomide, when should we expect to see the fourth line update on this asset? And could you just walk us through the broader development plan and timing around this, please? And then maybe just a follow-up on business development. Just how should we think about this going forward in terms of your therapeutic areas or mechanisms of interest? And what are you now thinking as your sort of sweet spot for deal size? Thanks.

Thank you. Samit?

Sure. I will start with mezigdomide. And certainly, the data that we presented already in single-agent combination has been quite interesting and certainly very helpful in terms of thinking of longer-term development plan for mezigdomide. The data update will be, I think, at ASH or at the next ASH conference that we will be able to find for the ongoing single-arm open-label study. More importantly, as you have seen in this scorecard that was presented by Giovanni earlier, mezigdomide has 2 Phase 3 trials planned to start in the coming -- in 2023 to look at the combination of trecholis as well as to look at the combination in the comparison versus pomalidomide. So those twp are the second line plus indications where mezigdomide is going to be tested, and we're looking forward to those initiations in 2022. I'll give it back to Giovanni for the BD question.

Thank you. And from a BD perspective, what I can say is we remain size agnostic. We have tremendous financial flexibility. What we look at is compelling science in areas that we know well and the opportunity to continue to further strengthen the outlook of the company in the second half of the decade and beyond, and obviously do that through deals that generate value for patients and for shareholders.

I know we're running short on time. I think maybe we have time to squeeze two last ones and maybe go to the next one, please, Sarah.

Absolutely. We'll take our next question from Mohit Bansal with Wells Fargo.

Great. Thanks for taking my question. Maybe a question on -- another question on Camzyos. So when we spoke to cardiology, there were some concerns raised by general cardiologists talking about ramps and how maybe only cardiomyopathy clinics, which more patients are better equipped to handle this. So one, is it true? And number two, like to what end Bristol can help make it easy for doctors. And the last one is like, do you know how -- what percentage of patient population is treated at specialty cardiomyopathy clinics. Thank you.

Thank you. Chris?

Sure. So with respect to the REMS and sort of how that's been received, as I mentioned earlier, the feedback on the REMS process has been very favorable from physicians. It's straightforward to get certified. We've spent a lot of time working with Samit's team before approval to make sure that the REMS program generally was intuitive and fit into how cardiologists generally treat patients. And so far, that work upfront as well as the education we've done is paying off. Cardiologists are generally seeing it as not a barrier, in fact, the fact that we have seen a large number of medium and small clinics get not only REM certified, but get patients onto therapy, and in many cases, get multiple patients on therapy is an indicator of the fact that the REMS program is, by and large, being seen as something that's very manageable for physicians and hasn't proven to be a barrier at all. Moreover, I think that the REMS program when we designed it was important to make sure that patients are initiated and initiated safely and monitored over the course of their disease. And that's exactly how this process is playing out at this point. So very happy with respect to what we're hearing playback from physicians on REMS.

Thanks, Chris. Can we move to our last question, please?

We will take our last question today from Robyn Karnauskas with Truist Securities.

Thank you for taking my question. All right. So quickly on Breyanzi. I mean, suggests still there's like a small fraction, maybe 20% of people eligible that can get the drug. So given that you have a really broad label, you're going into second line, how do you think you can improve this? What steps are you taking to improve the vein to vein or brain to vein time. And on deucra just a quick question there. For the moderate patients, how are you viewing -- how it will be positioned versus dermavan or Eliquis drug, the came in at a lower price, pretty clean safety profile. How are you viewing any step edits that might be required there? Thanks.

Thank you, Robyn. Chris?

Sure. What I would say is that on Breyanzi I think in general, the focus that we've had continues to be on -- if your question is around continuing the approve on the manufacturing side, the focus there has been on making sure that we're really on three things. First, on Breyanzi, you have to -- on cell therapy generally, you have to stay focused on operational issues. Obviously, we spoke about the issue that hit the success rates with this program in the quarter. But clearly that’s going to be one area of focus for us. And as part of that, you obviously are continuing to stay focused on improving turnaround time, and that's a clear focus for the manufacturing team. Above and beyond that, though, what I would say is most critical for us at this stage in the launch for both of Abecma and Breyanzi is to continue to be focused on vector supply and drug product supply, continue to increase that. We're working hard with health authorities to increase capacity on drug supply for Breyanzi at our existing facilities. We're also bringing on two state-of-the-art facilities in Devens, Massachusetts and at Leiden’s in the Netherlands that I think are going to be an important component of how we continue to expand the capacity for that product coming into the first part of next year. And then with respect to deucravacitinib, I think the focus, as we look at deucravacitinib is first and foremost, recognizing that the most important thing with this asset as you think about access generally is going to be the value story that you have to tell. And we have a very strong story to tell with deucravacitinib. As I mentioned earlier, we anticipate demand is going to be strong for this, also recognize that you have two Phase III studies that show head-to-head data against the current standard of care for the patients who are being treated with moderate to severe psoriasis. So we have a very strong story to tell with payers. And then in terms of those dynamics, I'm actually less concerned about competition with topicals and in particular, because remember, a lot of topicals are going to stay on board as you move into oral therapies and psoriasis. So I think the dynamics that we're most looking at are first, making sure that we provide very quick access for patients who have plans with open access. And as we talked about last quarter, in this market as opposed to other markets that we've talked about, many patients are covered by plans that will have open access at launch. And then obviously, we're going to have to continue to build volume in order to expand coverage for those that don't have open access at launch. And there, it's going to be all about driving volume and then leveraging that volume to get into a better access position over time.

Thank you, Chris. And from my perspective, let me just say again that what we're hearing from physicians all the time is that they consider Breyanzi as the best-in-class CD19 in CAR-T, and I look forward to the opportunity to have a significant increase in capacity at the beginning of next year, which will be important for us.

Now more broadly, I want to thank all of you for participating in the call. This was a strong quarter for the company. We have good momentum with our in-line business. There are very positive dynamics with our new product portfolio, and that positions us well for the second half of the year, which again, will be very important for the company. I look forward to continuing to answer your questions, and our IR team will be available for any follow-up you have. So thanks again, and have a good day.

Thank you. And that does conclude today's teleconference. We do appreciate your participation. At this time, you may now disconnect.