Making some people on the webcast feel as if they're a little bit late. But hey, it's the start of the year. Welcome to 2024. Anyway, my name is Chris Shibutani. I'm a member of the Goldman Sachs healthcare team. We are deeply grateful to the teams that were able to join us for this conference this very early date this year, and obviously, the point is to try and give voice and an opportunity to talk about some of the most interesting and intriguing stories across the healthcare landscape ahead of next week's confab. I am especially pleased to once again be able to be joined on stage by Adam Lenkowsky, who recently got a promotion to Chief Commercialization Officer from your role previously. So Adam, thank you very much for joining us. Thank you, Chris. Happy New Year. Yes, indeed, and especially appreciative to the IR team as well, Tim Power and the newest member, Janet Barth, which a lot of you veterans may remember. So some experienced soldiers in the field here for Bristol. And I would say that, you know, I appreciate you starting this year and ending your vacations, except Bristol, nobody in the C-suite or support seemed to probably have a holiday vacation. You kept us all pretty busy here, and we'll talk about that with all the deal activity. So it's been kind of a continuous process. So as I always like to do, I always like to start these conversations to sort of level set and let people in the audience know who the conversation is with. Maybe just a little bit of encapsulation of who you are, your background, your journey to this point, so that we understand the voice that you bring to the responses to these many questions that I will ask. Great. Thank you Chris and good morning everybody. I'm Adam Lenkowsky. I'm the Chief Commercialization Officer at Bristol Myers Squibb. I've been with BMS now for over two decades in a number of roles, leading our U.S. business, leading our international business, and over the last seven months, was assigned as the Chief Commercialization Officer for the company, and I lead our commercial org worldwide. And so I just want to say to start, what a, you know, important time it is for Bristol Myers Squibb as we embark on this exciting next chapter for BMS. As you alluded to, 2023 was an important year, particularly at the end of the year, tail end of the year. We've made a lot of progress setting a strong foundation for this year, including continuing to, you know, drive commercial execution across our new product portfolio, accelerating what I think is the best pipeline we've ever had as a company. And then, you know, finally, with the three transactions that we made towards the end of the year, really set us up for a very strong 2024. I think that's a perfect setup here. I think for investors, when you look across the pharmaceutical landscape, there has been kind of this phenomenon of obesity and everybody else. And everybody else is addressing a lot of the common challenges well known to the industry. Tremendous success with franchise products, a lot of good strategic decisions, commercialization, innovation that has changed healthcare, but inevitably, you have the loss of exclusivity. And those exposures in the portfolio weigh heavily on Bristol, and we think about that journey through this decade, particularly, you know, there's been kind of two measuring sticks if you think about what the dialogue has been from management to the street, thinking about how do we get from kind of the early part of the decade to the mid part of the decade, and then longer term, from 25- 30. So if I think about the team and what we've learned about, particularly as we've had this transition with Chris Boerner now as the CEO and you in your current role, one of the initial sort of markers or footprints that was set up by you guys was to make an adjustment to your view on the timeline for the intermediate term, the 2025, pushed out to 2026, when you felt as if some of the revenue ambitions that you have line of sight to were just in a different time frame. Talk about that decision, one that I think makes a lot of sense, but then it also seems to, you know, invite questions about whether it implies that there's an acceleration later. Maybe frame for us the thinking behind that reset, in essence. Yeah, happy to do that, Chris. Let me tell you what I'm excited about. As you know, we have launched nine new products, now 10 new products with Augtyro, launched right before the Christmas holidays at the back end of the year, last year. So we have that, coupled with six products that have gone Phase III studies last year, and another six that are moving Phase III studies this year. And adding on to that includes, you know, deals like SystImmune and Mirati, Karuna, and Rays, all of which are going to continue to add to the growth. So when I take a step back and I think about the, you know, the midterm and the short-term guidance. Mm-hmm. At Q3, we had stated that we would push out by 12 months our near-term revenue targets for just these nine products. And, you know, those w e moved that from 2025 to 2026, with delivering greater than $10 billion in sales. We also reaffirmed a $25 billion target. Mm-hmm. For the 2030 time frame. This is non-risk adjusted. So but when you look at that, we're talking about just nine products, adding on top these six new products that are Phase III, six that are coming in, and you know, the exciting opportunities with these new business development deals. We're going to be a very different company in 2030 with significant growth prospects well beyond these nine products. Yeah. No, I think that the moves that the company made, particularly over the last month, have clearly changed the equation in essence. But let's start with the base case, the foundational aspects, the existing business, the franchises, clearly, Bristol Myers long legacy in oncology, the combination with Celgene that gives you your presence. At the center point is obviously the immuno-oncology franchise. So let's talk a little bit about Opdivo. Has been such an important contributor to the healthcare landscape here. 2028 is a marker year in terms of when we lose exclusivity here, and naturally, investors are all trying to contemplate a couple of things, but importantly, w hat are the strategies that the companies are bringing to bear? What is the outlook of what impact that may have in terms of that revenue trajectory and that post-LOE period? When I think about what you guys are doing, amongst the approaches that make sense, for instance, is coming up with a presentation that is subcutaneous. So let's talk a little bit about that. Give us an update on where you are in terms of development with that formulation and how you envision, as the chief commercialization dude, how this will play out in terms of revenue mix, etc. Sure. Well, you know, starting with the short term, as you mentioned, you know, we're very pleased with the performance of Opdivo. As we talked about in Q3, in 2023, we're delivering on track, double-digit growth. We're gonna continue to demonstrate growth this year as we have a number of important launches, largely in the back end of the year, in early lung cancer, in first line MSI-CRC, in bladder cancer. And so although I'd expect to see, you know, not, not as robust, growth this year, we do expect to see growth for Opdivo. Mm-hmm. Opdualag is also a critically important product for us. One of our nine newly launched products, has become a standard of care in metastatic melanoma. Now, around the longer term, last year, we also had a positive trial for our sub-Q formulation. So why is this important? We expect to launch this either towards the end of this year, more likely in the beginning of next year. That's gonna allow us to convert business from IV to sub-Q. And what I've talked about, Chris, is, you know, we believe that it's about 65%-75% of our current Opdivo IV business. So let me just articulate what those patients are. So either they're adjuvant patients or patients treated with monotherapy, perhaps in melanoma or RCC, where you get four doses of Yervoy induction, and then you move on to maintenance, Opdivo monotherapy. Those are the patients that are ripe for conversion, and we've stated that we could convert about 50%. So there equates to about 30%-40% of our business that we believe we can convert. And importantly, you know, this is gonna be a sustainable business past our LOE and into the early 2030s. When we think about the commercial effort, inevitably it involves some anticipated dialogue with how the payers are gonna be viewing this. The context that they're seeing is that this is on the come, that there's probably some profile advantages for patients, particularly in the earlier line settings, that amongst the choices of what they, they have to sign the checks for, include options such as the availability of potential biosimilars or the IV version. Help us understand what some of the messaging has been in the dialogue that you've had with payers thus far? Yeah. Well, just a reminder that the sub-Q formulation of Opdivo is reimbursed as a medical benefit in Part B versus Part D. And so why do we do that? We did that to make sure that we are preserving physician economics, not disrupting the flow. Also, we think it's a huge benefit for patients and physicians. For patients, it's a five-minute in-office subcutaneous injection, and for physicians, it allows them to provide the injection while continuing to fill an infusion chair. And so this is really not on the radar screen of payers today. Got it. And then in terms of, obviously, you made mention of the Part B aspect, remind us what the implications of a sub-Q version are in the context of IRA. Yes. So we believe that because of the, you know, unique formulation that is a Halzyme derivative, dual moiety, that we will have IRA protection with our sub-Q formulation. Okay. No, that's very clear. Sticking to the immuno- oncology franchise, I-O, I-O combinations, Bristol actually being the only company that has more than one approved with a combination, and certainly it's been this Herculean effort from a research and clinical development standpoint, quite complicated. But with Opdualag, we're now two years past the approval in first-line melanoma. Market share, maybe give us an update on where the trajectory is. I think a little over a year ago, we were kind of in the mid- to high-teens percentage. I think the most recent updates, when we think about some prescription trends, is that that's continuing to progress, perhaps in the low-20s, mid-20s% range. Maybe just give some context for how accurate that assessment is and where you think the ultimate penetration can go to with Opdualag. Yeah, Opdualag is a really important growth driver for the organization. Our share today is now 25%, roughly, in first-line metastatic melanoma, so it is a standard of care. In fact, when you look at the total Bristol Myers Squibb share in melanoma, if you add Opdualag, Opdivo, Yervoy, and Opdivo mono, we have over a 60% market share combined in front line. And we think there's there's additional opportunity to grow. There are still about 15% of patients that are prescribed with monotherapy, either Opdivo or Keytruda. Mm-hmm. And also, you know, we've been making really good progress since NCCN guidelines have been updated to include Opdualag around a Category 1 status in the BF mutant population. And so we're seeing some nice uptake there as well. So we think there's some continued growth for sure for Opdualag into, you know, the 2024 and beyond. In the great, sort of verticals, oncology and immunology, the strategy is about these drugs being the gift that keeps on giving in terms of expanding indications. And in oncology, obviously, lung is sort of, you know, where the center of gravity is here. If we think about the Phase II data in the first-line non-small cell lung setting, you're doing a comparison against the Opdivo monotherapy arm. And typically, when we think about trying to figure out whether this will work, we benchmark against other work that's been done. Melanoma comes to mind, RELATIVITY-047, first line. Give us a sense for what your perspective is on whether there's a read across, and to how much we should believe that this influences optimism or not, in regard to the first-line lung opportunity? Yeah, well, you're right. Lung is important overall, and I'll talk a little bit about that in a minute. Because we were making really good progress with Opdivo, Yervoy, and our CheckMate-9LA study in growing in frontline. But as it relates to Opdualag, just a reminder, as we said, we should get the data sometime early this year, and this is a Phase II proof of concept study. So really trying to understand the safety and efficacy of Opdualag in combination with chemotherapy. Mm-hmm. We will get the data, hopefully shortly. We will interrogate the data to understand, does that, you know, does the data that we receive reach the bar, which is high with KEYNOTE-189? Mm-hmm. Or are there biomarker-specific patient populations that might be more suitable for Opdualag or Opdualag chemo in lung cancer? So we'll get that data very, very soon and make those decisions. We'll share the data publicly. And just, you know, importantly, as we talked about the $25 billion in non-risk-adjusted sales in 2030. Mm-hmm. When we look at that number, we could hit the $25 billion of non-risk-adjusted sales without even having a lung cancer approval for Opdualag. Mm-hmm. But I guess more holistically, when I think about the lung cancer approach at Bristol Myers Squibb. Mm-hmm. When you take what we have today with Opdivo, Yervoy, and 9LA, the potential for Opdualag, coupled with the recent approval of Augtyro, the acquisition of Mirati. Mm-hmm. And potential for RayzeBio as well gives us a lot of opportunity to penetrate segments of lung cancer, which, as you know, it's just not one disease, it's many diseases together. So we feel like we're in a very strong position to continue to drive leadership in the lung cancer space into the next decade. Got it. Okay, and then you're threading through nicely in terms of how the portfolio is building. I may try to maintain being a bit of a bully and thinking about the base business here, but we'll definitely get to Mirati and RayzeBio, et c., because that's very exciting. But then to finish up on Opdualag, thinking about the other indication is in liver cancer, hepatocellular, first-line data. When you think about Phase III structure, do you think about that market opportunity? A nd again, defining a profile that could be commercially convincing, would you believe that you need to do a head-to-head study versus Tecentriq and in combination with Avastin, as opposed to doing a head-to-head with Opdualag with Avastin? We'll also see that data as well when we look at Opdualag plus Avastin. Mm-hmm. I think what we have seen over the last few years is Avastin is an important component in order to demonstrate a survival benefit in liver cancer. Mm-hmm. But there's still a significant opportunity for a product to move into the HCC space. This is another Phase II exploratory study. We'll get the data, we'll see, you know, what it says. We had an earlier study that did not meet statistical significance, looking at Opdualag monotherapy in second-line HCC. But as I said, using bevacizumab has shown the ability to demonstrate a survival benefit, and then we'll have to assess what makes the most sense. How do we move forward? H ow robust the data looks, and similarly, you know, are there segments of the opportunity that we want to break into? Okay, let's transition over to CAR T here. Tremendous sort of innovation. The technical challenges of the logistics of commercialization, however, has been a bumpy journey across the board. We're seeing signs of improvement. Frame for us where we are in terms of, particularly for Abecma and the multiple myeloma dynamic here? Yeah, we've learned a lot over the last three years with both Abecma and Breyanzi. I think many of our competitors would say the same particularly with rates of supply. But, you know, we are in a much better supply position for both. In fact, coming into 2024, you know, we have a relatively unconstrained supply opportunity for both Abecma, and we're in a much better supply position for Breyanzi. You know, when I take a step back and I think about the journey for Abecma in particular, it was really a three-chapter story, if you would. We launched, as you remember, in 2021 Abecma. Mm-hmm. And it was the first BCMA CAR T coming to the marketplace. And quite frankly, there was just more demand than we could supply. Mm-hmm. And there was t his bolus of patients. Chapter two was the emergence of T cell engagers and products that had come in that are off the shelf, easy to use, and physicians, when they couldn't get access to CAR T, they would just simply just use a T cell engager. And then chapter three came. We started to improve our supply position. We're in a very good supply position last year, but so was Carvykti. And J&J made a lot of improvements as well as we did. And so we saw Carvykti start to accelerate for the treatment of later line multiple myeloma. And really, there were a big reason for that. Number one, was around the, you know, the perception of efficacy differences from Carvykti to versus Abecma, and we started to lose some business there. We would expect to see our sales in Q4 of last year that are actually lower than what we reported in Q3. This is an important focus for our commercialization organization, is really getting more competitive in this space. So we're doing a number of things, Chris, to accelerate our performance for Abecma. Mm-hmm. Firstly, we are expanding our footprint both in the U.S. We're in 100 accounts today, we'll be in 180 accounts by mid this year. The second focus is we've got to continue to educate around the appropriate sequencing of T-cell engagers and CAR T cell therapy. Mm-hmm. But I think most importantly is really closing that gap of efficacy between Carvykti and Abecma. And when you look at the data that's been presented, both real-world data as well as bridging data for Abecma, the efficacy is actually more similar than it is different. Clearly, physicians understand that the safety profile for Abecma is superior to that of Carvykti, but we need to go out there, and that's our focus as a team, go out there, be more competitive, and demonstrate the efficacy of Abecma in patients with later-line multiple myeloma. So with these steps, is there any way of maybe giving a sense for what the timeline for an inflection? We've actually seen sequential quarterly declines in the sales here. What's a reasonable expectation for when we might be able to see stabilization and a potential of positive inflection? Well, I think the inflection would come with a positive approval for KarMMa-3. Mm-hmm. As you know, the FDA has shared that we're gonna have an ODAC. They have not given us any information around the ODAC date as of yet. Right. The inflection really is the ability to move up earlier lines in treatment, and that's where I would see growth coming from Abecma. Are there strategies around sort of upside, downside scenarios as an outcome of the anticipated outcome? Well, certainly we plan for a positive and, you know, negative result, but, you know, certainly the upside opportunity, you know, would be important. We believe that, you know, the data that we have shared with the FDA, we presented it at ASH. We had a very robust KarMMA-3 primary endpoint outcome in PFS, and this was highly statistically significant. But what we also saw was the secondary endpoint was not a positive endpoint because the study was confounded by significant crossover. Mm-hmm. So we look forward to continuing to share data with FDA, talking to advisors at the ODAC, because, you know, we strongly believe that this is a product with a very good benefit risk profile and one that should be used in a triple refractory exposed patient population. Now let's transition and talk about some of the new members of the portfolio here. Okay. We're keeping it on oncology here because obviously, that's been very much a core franchise. You mentioned there was Mirati, obviously. Let's start there. What does that add? How does Mirati in Bristol's hands, you know, benefit and maybe function differently than as an independent entity? KRAS was always one of these holy grails for a long time in the late teens, fascinated investors. The commercial trajectory has been a little bit tougher. Durability of data has been not as optimistic as originally hoped for. Frame for us, what can you guys do with Mirati, and what will that mean? We are, from a business development standpoint, our focus, and you've seen this now, we're looking for first-in-class, best-in-class assets, and I think we have the same level of focus in our R&D portfolio as well. And so what we're excited about Mirati is, we think this is clearly a best-in-class KRAS G12C asset. Why is that? Number one, the combinability with with PD-1 therapy. We saw that Lumakras cannot do that. So we've started, or Mirati rather, has started a study, Phase III study, looking at a combination PD-1, Lumakras, PD-1 adagrasib in this Phase III patient population for first-line lung cancer. Secondly, you know, we'll get some data in the middle of this year, seeing can we explore the use in the less than 50% for combination therapy and potentially even triple therapy using chemotherapy combined with Adagrasib and, you know, PD-1. Mm-hmm. That's number one. Secondly, we have also, we see the commercial performance today in the market is done, the team's done very well. The CNS penetration has clearly been seen as a differentiator versus Lumakras in the marketplace, and we have a host of other indications in earlier lines that the Mirati team and we will be exploring together. The second thing that we really liked about the Mirati deal, and you saw this through the CVR agreement, was PRMT5. Mm-hmm. PRMT5, we think, could be a game changer in treating patients. It's prevalent in around 10%-15% of all cancer patients, and we'll be getting some data this year that we're presenting at a medical conference later this year. So another really significant opportunity, coupled with the G12D opportunity that presents itself, which is pretty, very prevalent in pancreatic cancer, and you know that's a very difficult cancer to penetrate. So what Mirati does, as well as RayzeBio and SystImmune, it helps diversify our leading I-O portfolio. For sure. Beyond I-O and gives us additional platforms in oncology to grow. And particularly with the PRMT5, this is an area that's certainly captured investor attention. We've seen that. We cover a number of large and small companies who are in all, in that space. Ultimately, what is the profile that you think will be defining of being a potential best-in-class? What should we be watching for when this data starts to play out more in the clinic? Well, I think it's really important, number one, to look at the safety profile of these assets. What we've seen with earlier PRMT5, the safety profile was just too toxic for patients to handle, and that's what we, what we really like about Mirati's asset and why we think that is could be a potentially differentiated asset. So looking at the safety profile coupled with robust efficacy and response rates over a host of cancer types, and that's what we'll be sharing at a medical conference later this year. And then to be pragmatic, when you think about the opportunity, for instance, in lung cancer or combinations, given the relative share distribution where pembro has become the dominant use in lung cancer, are you expecting that the ultimate commercial offering will be in combination there? And what can you do to better leverage what is existing within the Bristol house products? For these studies, yes. Mirati has started the Phase III studies with pembrolizumab. It is a standard of care in the United States and Europe for the treatment of first-line lung cancer, so the combinations will be with pembrolizumab. There are other opportunities with PRMT5 and as well as with, you know, the KRAS G12C agent to potentially combine with Opdivo and other tumors where Opdivo maintains significant share. Mm-hmm. We'll explore different potential opportunities to have, you know, a mix of PD-1 usage. Got it. Let's talk about RayzeBio, you know, there's been a couple of things in the second half of the year that have sort of broken the sound barrier, antibody drug conjugates, ADCs, being one of them, and we'll talk a little bit about a preliminary deal. But first, I want to get to RayzeBio Radiopharmaceuticals. You know, it's, it's almost reaching back into a really old-school toolkit, right? But bringing it into the twenty-first century in terms of targeted delivery. Tell us a little bit about what you think really gets you excited, from the potential commercial standpoint, and again, particularly within, you know, the, the toolkit that you guys have of your existing oncology business. So we've been looking at radiopharmaceuticals for a long time, and RayzeBio came to the top of the list because when I think about what RayzeBio provides, really three things I think are critical. Number one, it provides a platform for an IND engine. So you can see new products coming one after another in the back end of this decade and well into the next decade, based on the technology that RayzeBio has and RayzeBio offers, which is differentiated. The second thing that is critically important when you think about radiopharmaceuticals is having a state-of-the-art manufacturing capability, and RayzeBio also offers that, you know, for their organization. They've built a tremendous manufacturing facility in Indianapolis. And third, it differentiated from some other companies, is that they actually have a Phase III-ready asset with RYZ101. Mm-hmm. After in a post-Lutathera environment. So those three things taken together, we think is a great opportunity for continued diversification for I-O and a platform for growth into the long term. And if you had a chance to walk through the labs like I did and see the results that these platforms are delivering in patients, is phenomenal, absolutely outstanding, and some of the results are comparable to what I've seen with immuno-oncology and some of the toughest to treat cancers. Mm-hmm. And I think when the objective is to deliver some therapeutic for oncology, you're willing to go through a fair amount of effort. But nonetheless, the best pharmaceutical products, the best healthcare, best products in general are KISS, Keep It Simple, Stupid, right? And I can go back to 20 years ago, even like when people were just doing catheterizations and doing balloon angioplasty, and there was a little company called Novoste that had radiation delivered through those tips. And all of a sudden, the complexity of the logistics of getting the radiation and then the lead blocking and then having two doctors was like having cats in the squad fighting of managing the clinic. Not straightforward, was problematic, never saw the light from a commercialization standpoint. You think about the predecessor here that's demonstrated really finally some, you know, momentum from a commercial standpoint, Pluvicto with Novartis, and why, pun intended, this area seems to be hot now. You made it number two in terms of the manufacturing, but, I think I would love to have you make very clear what the strategy is on this delivery of the product itself, this commercial execution, because there are some really concrete nuts and bolts things. We're not baking crackers and off they go. We're making soufflés here, basically, right? Talk to us about the confidence that you have, because, again, we're in a potential dynamic where the efficacy profiles could be so compelling that demand could outstrip the ability to supply. So how do you prepare for that? What's the secret sauce in your playbook? Oh, remember, radioligand therapy is different than, let's say, cell therapy manufacturing. Okay. It's complex, but no t nearly as complex as what we've seen with cell therapy. So, as you mentioned, Novartis has really paved the way, you know, for many companies, set the playbook on how to effectively commercialize this. We expect to see, you know, RYZ 101 approved sometime in the 2027 timeframe, and our approach, in the meantime, is to keep RayzeBio as an independent company. As it relates to commercialization, though, it's just you're looking at the same centers that we're in today, some of the top academic medical centers that are treating patients across a host of different cancers. Our first indication, as I said, is going to be in a post-Novartis or post-Lutathera patient population. So we know that you're looking at about 250 sites in the U.S., about 400 sites worldwide, with a pretty limited footprint. And then there's just different, some different targets. You got to get to, you know, nuclear medicine to, you know, to talk to them about the delivery mechanism and, of course, the medical oncologist. So we certainly know what it's going to take to get to develop such an important platform like RYZ101, and the importance of effective commercialization, and we're excited to start to build towards that. Mm-hmm. Let me leave oncology a little bit and transition to another not-so-straightforward commercialization activity, which is with Camzyos, hypertrophic cardiomyopathy. I personally have tremendous respect from decades ago as a clinician of thinking about this patient population and the absurdity of these barbell types of treatment options, which were both inadequate and the innovation that's involved. But it's been a bit of a pain in the butt to try and get patients processed and through in the REMS, etc. Camzyos has been a product that has been essentially hacking the weeds through these fields. Now, you have a potential competitor coming up in the rearview mirror with Cytokinetics there. Talk about the dynamics there. Is there something that can be done to somehow skid the path through somehow a little bit, a nd whether you see a bullish or bearish scenario with having a competitor in this space? Is it more voices share a voice, or is it potential risk in terms of a winner taking all? Well, as a company, I'll tell you, we're so proud of being able to acquire MyoKardia, integrate Camzyos, launch that, and then really pioneer in this space where there's been nothing to treat the underlying disease of hypertrophic cardiomyopathy. The feedback that we received from both physicians and patients has been nothing short of outstanding. Our patients, within four weeks, are getting off the couch. They're for the first time in a decade, they're back to work. They're back to playing with their grandchildren. But, you know, taking a step back, and I think about the launch in the early part of 2022. Mm-hmm. When we launched that, it was also pioneering, really, one of the first REMS program as well in the cardiovascular space. Mm-hmm. So we had to do two things: educate on a new profile other than treating with beta blockers or calcium channel blockers, the benefit risk there, and also getting physicians comfortable with what the REMS program looks like, getting them signed up for the REMS program. How do you do the echocardiograms? And so that took some time to do that. And now, where we're at today is, you know, kind of in Phase II, we have seen, you know, significant growth for a product like Camzyos. In fact, we are averaging approximately 1,000 patients on a quarterly basis as we've seen steady and consistent growth. And, you know, Phase III of this launch now, beyond just tapping into these about 70,000 diagnosed patients, we've now taken a step forward to say: How do we bring more patients into treatment? Mm-hmm. And so we have launched, and we're investing even further behind this important product, launched both unbranded and branded direct-to-consumer advertising. And, you know, most companies probably wouldn't have done that this early. We thought it was so important to do it in parallel to, you know, getting those patients who are diagnosed, bring patients into treatment, who are diagnosed or perhaps feeling symptomatic. And we've seen a nice inflection for Camzyos since we launched that, you know, in the back part of the year. As far as Cytokinetics is concerned, one of the things I've said, and, you know, I continue to, you know, to believe this, you know, we saw the data just like you did. Mm-hmm. You know, we don't believe that there's any clinically meaningful differences in the data that Cytokinetics had presented on Aficamten. We have to see the totality of the data. They only presented around three endpoints, so we'll take a look at that. Mm-hmm. But, you know, we've expected the product to come to market, to launch, and I think having two products or more in this marketplace, when we look at a market that has only 25% of patients diagnosed. Mm. Certainly gonna drive more patients into treatment. And I'm very confident with the momentum that we have with Camzyos, that Camzyos will continue to take the lion's share of the business of obstructive HCM. And then sticking to cardiovascular briefly to touch upon Milvexian, obviously still in the Phase III process here, some updates relative to competitor programs that have had some disappointments, but then some other more recent data that's come from an IV formulation that actually seemed to sort of ratify a little bit of the potential safety differentiation. What's your view in terms of the mindset of how people should be thinking about the outlook for Milvexian? I know it's early, but. No, I think, number one, I talked about, you know, the 20+ years I've been with the company, and one of the things I'm most proud of is the strong heritage that we've had as leaders in the cardiovascular space with Plavix, sort of Eliquis, Camzyos, and hopefully with Milvexian. We remain very confident in the three studies, as you know, that we have running in parallel- Mm-hmm. In atrial fibrillation, in secondary stroke prevention, and in ACS. We took a really disciplined and methodical approach to looking at what was the right dose in atrial fibrillation with our partners at J&J. We used a very similar approach that we used for Eliquis back pre-launch. Mm-hmm. As you know, we presented data from our TKR study. We explored a wide range of doses and ultimately found that, you know, the higher dose, which we put into our AFib clinical trials, demonstrated efficacy that was comparable when you're looking at cross-trial comparisons to, to Eliquis, with a superior bleeding profile. So we remain very confident in the hypothesis that we have put forward in a, you know, a higher dose will yield significant benefit for AFib patients. Got it. Talking about dose is a good segue to talk about the TYK2 space. It's been novel, certainly the oral therapeutics for advanced immune treatments. So TYK2 obviously has been out there, again, kind of a little bit bumpy path, success with psoriasis, IBD, clinical development challenges. Talk to us about sort of the commercial outlook and the revenue trajectory here, because there's a lot as we're at this inflection in the early 2024, thinking about insurance coverage and when we see the benefits of that. Yeah, thanks. Obviously, so TYK2 is a key growth driver for the company in the short term as well as into the long term. The two things that I talked about were critically important for this brand. It was, number one, making sure that we are driving demand, and that means improving our depth and breadth of prescribers, and I think we've made some good progress there with Sotyktu. The second, in such a highly competitive category l ike Sotyktu, you're gonna see some market share fluctuations from quarter to quarter. We've seen some of that with, with Sotyktu, already. However, you know, access and reimbursement is critical, and I'm pleased to share with you really for the, for the first time as we come into this new year, that, you know, we were able to secure ESI, in a one-step edit position, and that's about 30 million lives are now under ESI. So when you take CVS, which we were able to secure last year, coupled with, ESI, we now have over 55 million lives that are covered under zero or one step edit. Now, there's one more PBM. Of course, the three PBMs represent about 80% of the lives in the United States. Mm-hmm. We are working feverishly to try to secure access there as well over the next, you know, several months, and we are hopeful to have a positive result that will allow patients to get on treatment easier and also be able to push patients out of the hub more readily than we have. So we continue to see strong growth opportunities with Sotyktu in the short term, and in the longer term, opportunities with SLE, opportunities with PsA. Mm-hmm. All those are coming in the middle of the decade, you know, assuming positive studies. In 2024, actually, we're gonna get some PsA data, right? We should get data in the 2024-2025 timeframe for PsA. And what's important there, not just the opportunity alone in PsA, but there are about 30% of patients in PsO that have comorbid joint involvement. So that will also help to solidify the Sotyktu perception when patients are being treated in derm offices who may have, you know, you know, comorbid or concomitant joint involvement. Mm-hmm. Then maybe a little bit of a help with thinking about pricing strategy. We're at an interesting juncture here. So many of the, you know, iconic, multibillion-dollar franchises in immunology are now seeing biosimilar challenges. We're seeing the emergence of the, you know, late-stage development of some advanced oral therapies that like to use vocabulary like biologic-like efficacy. And so theoretically, you could be getting something of a different presentation there. What's the decoder ring for the right pricing strategy if we think about this? And there was one other thing I'll add, which is that as additional indications come on board, we learn that the negotiation process often involves giving a little bit there. So what's the framework for thinking about immunology pricing as we go into 2024? Well, immunology, as you know, this is a highly competitive and also a highly rebated category. Mm-hmm. There's no question about it. In order to secure early access, these are, you're looking at significant rebates to, you know, to get into an open access or a one-access step position. Mm-hmm. As more competitors come in, as biosimilars come in, I think you'll continue to see downward pressure on pricing. One of the things I talked about when we speak to PBMs, they're struggling with, How do I treat biosimilars that are in the market today? We know Stelara will come into the market in a biosimilar. Mm-hmm. Likely in the early 2025 timeframe. Correct. And it's that push and pull of kind of political pressure to economic pressure that they're facing. And there was just an announcement you may have seen yesterday from CVS on one of their formularies. They decided to put a biosimilar formulation on the same tier as t he other branded players. Mm-hmm. We've seen that in some of the others as well. What we haven't seen quite yet, other than some downstream employers pushing for this, is biosimilar-first formularies. But I could see that, and I can envisage that happening over the next few years as you see more biosimilars coming into the marketplace. And then the role of these advanced orals and the strategy for figuring out how to define the right pricing for the advanced orals, like Sotyktu? Well, I can't speculate on the right pricing there. I think the market has already set the pricing. Mm-hmm. And that will continue to likely, you know, erode over time. Mm-hmm. As more competitors and biosimilars come in. That said, from a commercialization standpoint, Sotyktu has already set a very high bar. Mm-hmm. And so for another company to come in with an oral product, you know, whether it's an oral IL-23 or an oral TYK2, it has to show some meaningful difference, we believe, than Sotyktu demonstrates in the market. Mm-hmm. And with that, by the time that does come into the market, we'll have additional indications like the ones I talked about, like lupus. Mm-hmm. Hopefully, like Sjögren's, like PsA, making it more challenging for others to enter the marketplace. Got it. Maybe remind us, when are we getting lupus data? Lupus data is in the post-2025 timeframe. Okay, great. I know that was identified as a clear target there. A couple more questions, but transitioning over to a product that's launching Revlimid. MDS, an opportunity to get the TAM more broadly defined. How's that launch going? What should we be thinking about? Yeah. We're really pleased with what we're seeing with Reblozyl. Now, it's still early days in the launch. We launched at the end of August, but we've seen, you know, a nice inflection for Reblozyl since we launched the COMMAND study in the U.S. Mm-hmm. We would expect to see approval in first line in Europe in the first half of this year as well. What we're seeing is uptake, a rapid uptake in the community setting. Right. Across both RS positive and negative. Initially, we had heard from academic medical centers that they were taking a more measured approach on uptake in the RS negatives until the data was presented, final analysis for Reblozyl at ASH, and they saw the durability of response for the RS negative population, which looked comparable, if not better than the RS positive. So we have seen very nice uptake and expect Reblozyl to be a key driver of growth for the company this year and beyond. Okay, great. Let's turn to the, was it the post, the day after Christmas, Karuna? Mm-hmm. Neuroscience. Historically, presence in neurodegenerative disease, and then the legacy goes way back to having a presence with neuropsychiatric disease. So this was quite a get. Talk to us about how you're framing the, the commercial opportunity here. Well, Karuna is incredibly exciting because it really accelerates our re-entry into the neuroscience space. As you know, we've been out of neuroscience since we launched Abilify, and so we've been out of neuro for about a decade. But when we looked at the landscape, we thought this was a great fit for Bristol Myers Squibb because of our focus on neurodegenerative disease and adjacent opportunities. Mm-hmm. When we see a product like KarXT, you think about a few things. Number one, you have an asset that essentially is de-risked with a PDUFA date coming at the end of September. September. So we plan to launch sometime in, in Q4. The second area, this is, this is an opportunity that has multibillion-dollar potential because they have not just one indication that's already read out positive, but multiple indications in Phase III. So it could be the first product that's approved ever in adjunctive schizophrenia. Mm-hmm. It has a Phase III study in Alzheimer's dementia psychosis. Mm-hmm. I, you know, I hearken back to when we launched Abilify now over two decades ago. There has been nothing in this space that has shown any differentiation from products like Zyprexa, Abilify, Risperdal. When you think about products like KarXT, it brings an unsurpassed level of efficacy without that significant baggage that those products bring in schizophrenia and other, you know, diseases, mental health diseases, such as weight gain, EPS, akathisia, excessive sedation. Mm-hmm. This product is really poised, I think, for significant leadership opportunity in schizophrenia and well beyond, and even beyond the the Alzheimer's dementia indication. We've talked about opportunities in Alzheimer's agitation in bipolar mania. Mm-hmm. And we plan to launch a long-acting formulation as well. So this is a pipeline and a product that we think is gonna drive significant growth in the back end of the decade and well beyond, and also get us back into neuro as we're starting to bring our kind of our neurodegenerative platform, our anti-tau, into a Phase II trial. Mm-hmm. Yeah, I mean, there's the opportunities are there. When you think about how to slice the different segments of the market, there's clearly schizophrenia, there's monotherapy, there's combinations. The terminology of cycling through therapies often gets widely used, which, to me, I interpret to mean that we're still having a very difficult time identifying the right patients and that the chronology of individual patient disease is just very unpredictable. But particularly on long-acting formulation, this is something that's always kind of puzzling to me. When you look at existing LAIs, for instance, for Abilify, the percent penetration in schizophrenia is pretty modest. It's I think it's maybe teens-20% or so, still higher in Europe. Why is that? Well, it's about a $6 billion market right now, the LAI market, and we see continued growth there. Right now, the, you know, the Invega family of products. Yeah. Tend to have a dominant space there. But in schizophrenia, we believe this is a ripe opportunity. It's just the issue has been the products that have long-acting injectables, they have these, you know, significant weight-limiting side effects, as you talked about. Right. That's why you see 60%-70% of patients cycling from one product to, to another, because you have these weight-limiting side effects that make patients non-compliant. We think that that will improve the compliance rate. Right. Moving to. But the relative penetration of the long-acting in the U.S. seems to be relatively modest. Certainly compared to oral formulations. Okay. For sure. Uh-huh. But schizophrenia, we think, is a really good opportunity, but even better, potentially, in an Alzheimer's patient population. Mm. If you think about. Right. What that can bring there? Caregivers, etc. By the time that we launch the Alzheimer's indication, then we would expect to bring our long-acting formulation into the marketplace. Got it. So the deal anticipated close sometime in the first half of 2024, Opdualag in September, meaning that the team that's actually on board is the one that's actually doing all of the, you know, seventh and eighth inning commercial prep work. As you peer behind the curtain, how are you feeling about the work that they're doing, and what will you inject into that process as Bristol? Well, we have enjoyed having multiple meetings with the Karuna team. They've done a really nice job in starting to build a commercialization infrastructure to get ready to launch. They put individuals on their commercial teams, access, medical, marketing, sales, that have extensive experience. But we know the work that needs to get done, that's in front of us, in order to be successful in launching this critically important product. So what we will be doing is, in parallel, you know, we'll be doing the groundwork as well to ensure that we are ready for this important launch. And then to close, since I love talking about people who are not here, there's an important adjustment that's happened in the C-suite. This is C-suites Unscripted, so this wasn't necessarily scripted, but Chris Boerner is our CEO now. Clearly, he's been a very busy guy. I think, the Christmas holidays basically did not happen for him. Help us, maybe from your perspective of working, and you took on his seat as the chief commercial officer, something or things that you think might be underappreciated, that we should keep an eye out for. You know, he's still a little bit of a, you know, objectively two-dimensional guy for a lot of people. What should we, you know, keep an eye out for? What maybe is underappreciated about Chris Boerner? Well, as I said, it's such an exciting next chapter for Bristol Myers Squibb, particularly with Chris at the helm. I've had the pleasure of working with Chris since he joined the company in 2015. As you said, I succeeded him in the CCO role. I think you've already seen Chris put his stamp on the company with the number of deals that we were able to transact in the back end of the year. Chris brings, you know, a tremendous sense of urgency. He understands our business better than anybody. He understands the importance of kind of how do we navigate through the back end of this decade, the challenges, the opportunities that are in front of us, and the focus on bringing value to our shareholders and the importance of focusing on the patients that we serve. I think with Chris, what people probably don't know or appreciate, because Chris has been so present as Chief Commercialization Officer for the last four years, people probably think of Chris as this, you know, pharmaceutical legacy person. But in reality, you know, Chris grew up and spent much of his career in the biotech world. Mm-hmm. And what that brings to, you know, to us and having him as the leader of our company is that, number one, he understands the importance of R&D, and what I appreciate about Chris, the importance of the commercial R&D partnership, which is more important now than ever with the rapidly changing landscape. And so Chris is, in my opinion, the perfect person to lead Bristol Myers Squibb, you know, over the next decade. Yeah. No, certainly, he cut his teeth in the golden age of Genentech through Desmond Hellmann and many legacy people in oncology. So I think, there's a great toolkit there. And I will actually add that I thought that he takes a very well-appreciated approach or an underappreciated approach. But I asked kind of a mean question during the R&D day, and my team and I were my associate and I were kind of hiding out afterwards because I thought it was kind of a mean question. And he kind of sought me out afterwards and really wanted to continue to engage. And that ability to be in this listen, productive, sleeves-rolled-up kind of mindset, I think, is one that characterizes him and the C-suite. So, thank you for being a great guy and coming here so early after you basically had your holidays ripped away from you with all the deals. But I think it's an exciting time for the company. We'll be looking forward to a lot of the progress and, these deals closing and watching the portfolio grow in 2024. Adam Lenkowsky, we appreciate it. Thank you. Thanks for having me, Chris.