Okay, let's get underway. Good morning, everybody. Welcome to the second day of the 44th Annual Goldman Sachs Healthcare Conference. We are very pleased to have Bristol Myers join us. Today from the team, an opportunity to really focus in on some of the key business segments. We have Lynelle Hoch, Senior Vice President, Global Cell Therapy Franchise-
Mm-hmm.
live and in person.
Yeah.
You were impressive on Zoom at ASCO.
Yes.
Roland Chen, who is an SVP.
Mm-hmm.
in the cardiovascular development, also a very strategic pillar in terms of the portfolio for Bristol. What I like to do is make these conversations, some connectivity, that you're not just mouthpieces for Tim and Nina, but we know a little bit about who you are, where you came from. A quick snapshot on your professional journey that brings to bear, so that we know how you think about stuff, communicate what's been in your dark and mysterious past. Lynelle, you first.
Okay, my dark, mysterious past. Lynelle Hoch, I've been at BMS for 27 years. I came through a less infamous acquisition known as DuPont. I spent five years at DuPont. I'm an engineer by training, started at DuPont Chemical before I moved over into the pharma business. I thought it was far more exciting than my engineering days. I've navigated my career at BMS across multiple different therapeutic areas. I'm probably most known as leading the U.S. IO business during its series of launches across both Yervoy and Opdivo. I was leading the U.K. and Ireland business before I got asked to come back and lead our cell therapy franchise, which in BMS's model, means I'm accountable end-to-end from the research through the manufacturing to commercialization.
Terrific. Roland?
Yeah, no. Thanks, Chris. It's great to be here.
Mm-hmm.
I head Cardiovascular Development at Bristol Myers Squibb, where I've been there for about 23 years. I am trained as a physician, but also as an engineer. You learn new things about colleagues, every day. You have to sit up on stage.
There you go. You're the first to admit about that.
Yeah. To learn them. Prior to my role as head of Cardiovascular Development, I headed Clinical Development for really our, what would be considered our non-oncology portfolio, previously. Before that, I had the chance to head our Pharmacovigilance and Epidemiology Group. Again, it's a pleasure to be here, Chris.
Okay.
Thank you so much.
Terrific. I think a logical way to think about this is maybe to talk about the cell therapy business first.
Mm-hmm.
Go on to the cardiovascular side. I'll try and keep an eye on the clock so that we're fair.
Mm-hmm
Beyond talking about sort of the key issues that all of us care about, I will thread in a little bit of a discussion about your view on the implications, potentially, of the IRA,
Mm-hmm
development strategies, et cetera.
Mm-hmm.
Fresh off of ASCO, EHA is also in the air. A lot of excitement over CARTITUDE-4.
Mm-hmm.
Talk to us about what you see as sort of like the most important takeaways from those data presentations.
Yeah. We went into ASCO very confident at Bristol Myers Squibb, and came out more confident. Why do I say that? For one, we got to see the Multiple Myeloma Research Consortium real-world data, that essentially, from last year to this year, replicated Abecma's efficacy, safety, and manufacturing reliability that we saw in KarMMa. Obviously, that's extremely meaningful. As you can imagine, physicians, they want to make sure in what they see and get from an asset, that it delivers for their patients in the real world, and that's certainly what they got to see in the real-world data, despite the fact that 75% of those patients would not have qualified for KarMMa based on their comorbidities. We were quite excited to see that, and again, the manufacturing reliability at 94% is extremely meaningful in this field.
In addition, when we think about KarMMa-3, we think about a triple-class-exposed patient population. 100% of our patients were triple-class-exposed, 95% of those being dare refractory. Understanding the context of that data and the context of the competitive set, we walked off the meeting feeling very confident, one, based on KarMMa-3's performance, but also two, in our statistical methodology, congruent with the FDA, we feel we're in a very good position in the multiple myeloma marketplace coming off that meeting. The final thing I'll say is, of course, we had other data there on CLL for Breyanzi, I can hold that because I think you might have a question for me on that field. Yes, in multiple myeloma, we felt very confident on that data.
The final thing I'll say, what is clear to us, both on CARTITUDE-4 data and with KarMMa-3, as well as T cell engagers, is you're going to see BCMA-targeted assets move earlier and earlier lines.
Mm-hmm
W hich means you're going to have a large post-BCMA marketplace, and we were quite excited. I am fresh off Frankfurt, Germany, maybe a little bit jet-lagged, flying here from there. I seeing the data for our GPRC5D, which is now in over 60 patients, we're seeing consistent efficacy results and a side effect profile. With that one-time dose, we're seeing really good safety profile, unlike the T cell engagers, where you're seeing ongoing, continuous hit of that target, which can cause some problems from a on, you know, target, but off-tumor side effects. We're quite excited overall in multiple myeloma, both on our competitive position commercially today, as well as we think about well poised with our pipeline.
Terrific. A veritable cornucopia of opportunity in cell therapies. Let's see what spell check does on the transcript with that one. Sticking to CARTITUDE-4, are there subgroups that you think are most suited to Abecma based on the data?
We hear from a lot of different KOLs that they certainly look at these two assets and say to themselves, "It's such a fragmented marketplace," and for them, they see enough space for both. What we often hear is sometimes patients greater than 70. Obviously, that's a large segment of multiple myeloma when you think about that disease state. It's something they think about the overall profile of a drug, like Abecma is very advantageous for based on its efficacy, as well as its safety profile, which is extremely important consideration set when they dose these patients.
When we think about what the sort of the requirements are from a regulatory standpoint, how do you think in these earlier line patient populations of the importance of overall survival data?
I think it is important, but I think more and more physicians are understanding, listen, how we design trials to be able to be patient-centric and get these assets data into the market quickly, as well as to allow in design crossover, is the best thing for patients. I think more and more physicians look at other markers to determine their satisfaction on whether the efficacy will hold up. We feel very confident on our package as we think about our current and ongoing dialogues with health authorities.
Let's talk about the
Mm
ongoing commercialization of Abecma. It's been a few years. There have been challenges. We'll talk a little about the manufacturing, but maybe you can help us with sort of, any sort of feedback from the field in terms of what's working, how is there success, what could improve? Again, it's sort of like really in the trenches with the commercialization aspect now.
Yep. Obviously, with autologous cell therapy, I think every manufacturer has been on a journey of learning, kind of dealing with heterogeneous patient populations coming in and having that variable patient material, oftentimes much sicker than what you saw in your clinical trials. I think what we've been able to learn in our over two years is that you're basically taking those learnings, being able to apply those, and what you're seeing from physicians and what they're saying is, and we've heard this quotes from many very tough physicians have said, "You've figured it out." I don't know that I would ever say we figured it out, what I will say, when you see 94% manufacturing success rate, that is probably as good as you're going to see it in autologous cell therapy.
What physicians say back to us, when we patients, that we go ahead and apheresis and commit to go on to cell therapy, and when they get that product back in a very fast turnaround time and with a high success rate, that is extremely meaningful to them and their treatment sites. For us, from a commercialization, our folks can focus on differentiating the asset versus spending their time defending kind of our manufacturing operations. That's a great place for the commercial organization to be in. They're certainly excited to be in that space.
Let's talk about manufacturing and supply. This is not a simple process, and it's one, again.
Mm
Where the word journey probably should be applied to. Talk to us about where we are and where you think the progress could be made as we head into the back end of this year, then naturally over the next couple of years. There's a couple of specific facilities that we should toss around, names like Devens.
Yeah.
Libertyville and stuff. Just update us on where we are.
When we talk about manufacturing, we think about it in three buckets. First and foremost, we think about vector supply, so our ability to have enough vector to be able to meet the demands in the marketplace, and that has transparently been a challenge for BMS. We single-sourced adherent lentiviral vector for both of our assets, what became a challenge, and you've heard us report thought on multiple earning calls and multiple investor dialogues. Clearly, we've had some successes on adding additional suites, including one for Abecma just this year, of adherent lentiviral vector, but most notably was the addition of Libertyville. That facility will be our first move to dual sourcing, and as part of that dual sourcing strategy, we'll be internalizing vector. That obviously gives us a lot more opportunities to ensure that vector is not a constraint.
In addition, Liberty Ville represents our ability to accelerate into next-generation technology, both suspension and Hyphecan, which, as you know, gives you greater yield of vector. The vector becomes more of an afterthought than really the storyline, which it has been for us on manufacturing. The second component we look at is drug product capacity. Our ability to deliver from a drug product capacity, it starts with your state-of-the-art facilities and your ability to ramp in partnership with health authorities, those facilities. You just had said, we have just announced Devens, which is now our fourth state-of-the-art facility, our third commercial state-of-the-art facility. We have one in New Jersey, in Summit.
We also have a facility in Boston. Now we have one in Devens, Massachusetts. We will have one aiming for 2025, early 25, for Leiden, which will really help our European markets in that standpoint. The final component is how successful you are at hitting dose, and when you hit dose, how successful are you having in-spec product, which is important when you think about commercialization and generating revenues. What we have seen is great success, as I've already articulated, on Abecma, so I won't underscore that again. On Breyanzi, we've been on a bit of more of a journey. We are starting to see some great progresses there as well.
I would say we are in a great position and growing in strength across all three of those dimensions.
Help make us a little bit smarter and geeky about in-spec. What are the kind of numbers that you're currently at and that we should ultimately be thinking to asymptote to, in terms of thinking it's like, yeah, they've got this under control?
Well, I'll make this, not because you guys can't handle the complexity, but it could take you hours. For those of you who know how many specs we actually have to hit, and it depends on asset, and it also depends within an asset across the different lines of therapy, because we have different spec release for each indication as well, which is not something to feel like, and we're working with the FDA to try to harmonize specification releases. Typically, what you see is 97% of our products are in spec clinically, which means we can administer it, so it gets to our patients.
That's the great news, that patients today, for both Abecma and Breyanzi, regardless of its commercially in spec, get our product because it's clinically in spec, which means it was in the same specifications, your efficacy and safety was demonstrated in your clinical trials. For Breyanzi, it is, you know, commercially in spec, it is our specs through the BLA process were tight. That tightening has been very challenging for that asset. Abecma, we were more successful in our BLA process, and we have specs. As I said, we are at 94%, so we have quite a high in-spec rate as well as manufacturing rate on Abecma.
Got it. Let's talk about GPRC5D. It's like the password
A lot of letters, lot of letters
that you'd never want to know. Is there an in-house slang shorthand for this one?
5D.
5D.
We call it 5D.
Okay.
You know what's so funny?
It's 5D, guys.
I said 5D to a customer. He looked at me, and he's like: "What?" I said, "Oh, sorry, that's in-house. It's too many letters for GPRC5D, but yes.
Okay.
5D.
Highlight us on 5D, the data that was recently presented.
We're quite excited about this asset. For one, as I articulated earlier, with a larger and growing post-BCMA marketplace. It's important for me to point out, for those of you who've been following GPRC5D, we first revealed data at ASH, and then we've had more follow-on data, as well as those expansion data at EHA. Now over 67 patients have been exposed to GPRC5D. What are we really excited about on this asset? For one, its efficacy profile has been quite impressive. As you've seen across the different doses, very high ORRs and CRs. What is also equally exciting, what people were wondering was: What would a CAR T 5D asset look like in a patient population juxtaposed to the bispecifics or the T cell engagers, I should say?
What we're quite excited to see is, again, back to a combination of it's a one-time dose and getting that dose correct, as well as looking at our manufacturing process. We're really seeing very manageable side effect profile, which is quite exciting for the field, and we heard a lot of buzz from KOLs. As a matter of fact, the line of people that would like to be doing this clinical trials with us is quite extensive because they're starting to see the impact of this asset.
What's next? When's the next time that that'll, you know, appear with added data?
We haven't disclosed that, but I can tell you we're working quite fast. As you can imagine, being first and best, which is what we think we have in this asset, is critical. We'll be working quite fast with health authorities, and so you guys will certainly... As soon as we have data that we will release, you'll be sure to see it.
Okay. We'll keep asking. On Breyanzi, let's talk commercial utilization, second versus third line. What's the rough split now, and what are the trends looking like?
Yeah, the demand for CAR Ts in Large B cell lymphoma remain extremely high. I think people really appreciate the curative intent of the CAR Ts, in particular, two of them. What I would say is, right now, the fastest-growing segment of our business is second line. That best-in-class profile that people see with Breyanzi, with a combination of very strong, deep, and durable efficacy along with a safety profile, that profile means more and more as you move into earlier lines because that safety profile, as you can imagine, is extremely important treatment consideration as physicians treat earlier lines. Definitely seeing a greater mix there. It's around 60, 40, right now
Yeah
for second line versus third line. We certainly see both lines growing, but the fastest growing is second line.
The clinical push to the outpatient setting, I think the last comment from the house was that 15% to 20% of patients are on an outpatient basis. Is that continuing to be the case? Where do you think that could be in a couple of years?
It continues to be around 15% to 20% of outpatient. I will say we just had a great win this week with CMS. CMS will now be adding Breyanzi as part of their ASP. You know, they quarterly report out ASPs. That will be starting July 1st. Breyanzi will be a part of that mathematical equation, which, as you can imagine, can be a barrier to a hurdle for the Medicare population to be treated in the outpatient when you don't have an ASP number. That also, I think, will help on any kind of, you know, resistance facilities might have been having on using outpatient. I do think it will grow for sure. I think the confidence people are gaining on Breyanzi and its overall profile means that you'll probably see more and more outpatients.
It's always important, I think this room knows this, outpatient isn't like pure community, oncology play. You still have to lymphodeplete these patients, you still have to bridge these patients, and you still have to monitor these patients. Outpatient, meaning they won't be hospitalized for as many days, and as you saw in real-world data, the hospitalization, rehospitalization data on Breyanzi is very strong.
Indeed. Thinking about another intersection is once again the potential entry and competitive threat and the choices with bispecifics.
Yep.
How are you thinking about that here in this indication?
We continue to hear from physicians, whether it's at ad boards or market research or out just in general interactions with customers. The CAR T efficacies is really the bar, and when they're thinking about going for a curative intent, they think of CAR Ts and CAR Ts first, and they do think sequentially, starting with a CAR T and going to a bispecific is still the right strategy. The counterpoint to that is, do I have a slot, right?
I think as we and the field continue to increase our capacity on CAR Ts, which we have been doing, you're going to see more and more physicians continue to move towards a CAR T first, and that for patients who cannot get access to a CAR T or for some reason, it's not a consideration set, then there's an obvious option with a bispecific.
The competitive dynamics with Gilead and Yescarta, there's so many factors that are
Mm
correction factors, whether it's supply issues, et cetera. How do you see the ultimate share splitting out? We talked to a lot of KOLs, where it's just like there's an appetite for what's available and logical, but ultimately, is there some sort of framing of the competitive dynamic and the share that you can help us with?
Yeah, we don't kind of get into the whole kind of framing of the share, but what I can tell you is we're quite confident on Breyanzi and its potential into the future, and I say that for two reasons. One, of course, we feel strongly about its best-in-class profile in large B cell lymphoma, but also based on kind of the data that we presented at ASCO and CLL, we are the first and only CAR T to demonstrate those deep and durable response in CR, despite others trying in a pivotal study. We're quite excited about our ability to go breadth-wise, as well as recent releases of follicular and MCL, which will be shared at ICML this week.
When you think about Breyanzi, we think now as the broadest array of B cell malignancies that Breyanzi will be able to play in to drive our share and our volume, as well as our best in profile in large B cell lymphoma. We feel quite good about our position over time with Breyanzi.
As I promised at the beginning of our discussion, to wrap up on the cell therapy, when I say IRA and cell therapy, investors should be thinking what?
I think it's still early for all therapeutic areas, but particularly for cell therapy. As you know, most of cell therapy is administered in a hospital, so mostly Part A, so the impact of cell therapy in IRA is lower. Even inside of Part B, which we just talked about, expanding into outpatient, I think it's still early days, you had kind of started your conversation with, Does it have you thinking differently about research and development? I would say no. I think we will continue to push innovation and push cell therapies where we think we can have curative intent, IRA is not changing kind of our pursuit of that aspiration.
Terrific. Roland, let's move on to the cardiovascular side of the equation here with Camzyos in particular.
Sure.
An innovative product, clearly a commercialization challenge. You're basically changing the paradigm between, like, two very inadequate, difficult options from the treatment standpoint. There's a lot of hacking of the weeds here. An important label expansion opportunity is coming up with the VALOR trial results, where we have a PDUFA coming up this month here. When you talk to the folks in your team, development-wise, and thinking about commercialization with physicians, how impactful will the addition of this to the label be?
Yeah. Thanks for the question, Chris. When you think about VALOR, maybe stepping back, I mean, VALOR was a double-blind, placebo-controlled study of Camzyos versus placebo in patients with highly symptomatic obstructive HCM. These are patients who don't have a lot of treatment options, other than a highly invasive procedure, that is SRT. When you think about the results of VALOR, what we saw really are two things. We saw that it reaffirmed the profile of Camzyos, as evident in the Explorer study. That is with respect to both efficacy and safety. I think more importantly for the patients in the VALOR study, and hopefully more broadly, what we saw were very clinically relevant and statistically significant, of course, differences in the numbers of patients who remained eligible or elected to undergo SRT.
Again, the clinical importance here is that, you know, these are highly invasive procedures as really a last-stop option for these patients who have refractory HCM. Camzyos offers a potential other option there, and I think with that, and to reaffirm, again, with additional data, and it continues on in the longer term, the efficacy and safety profile of Camzyos, a chance to meaningfully impact the unmet need these patients experience. We think really important impact because of the clinical relevance of these findings.
Right. You're threading over to something that's really foundational to thinking about what the peak sales opportunity, and that's the duration of benefit, long-term extension studies. You've presented some data to date. Talk about your view of the likelihood that Camzyos will be convincing and compelling in terms of being able to sustain and maintain the kind of benefit longer term.
It's a really important question, Chris, because when you think about the amount of time that you have to study these compounds in the short term, you know, it could be 30 weeks, it could be 16 weeks, and so on. We presented data, for example, at the previous ACC. We presented data with Camzyos used up to 84 weeks. When what we see there is data which reaffirms, again, sustained improvements in cardiac biomarkers. We see sustained improvements in NYHA class improvement and in left ventricular outflow tract gradient with a safety profile that continues to not show anything new, which gives us confidence in the longer term. I'll also say that we presented earlier this year at ACC some interesting data, based on CMR, which shows favorable cardiac remodeling effects.
Again, something that's very interesting in terms of the promise and the potential of Camzyos, in terms of things such as left ventricular hypertrophy, as well as volumes that we see in the longer term. Finally, you know, we presented this at AHA in 2021, some data, even in the non-obstructive form of HCM, where we saw, again, sustained improvements in cardiac biomarkers, NT-proBNP, other biomarkers, but I think also importantly in echocardiographic parameters, which suggests that Camzyos had favorable effects, in this case at 48 weeks, on parameters that are important: left ventricular performance, diastolic function, filling pressures. A number of pieces of data that give us confidence in the longer-term profile of Camzyos moving forward, Chris.
Great. Obviously, the indication is for the OHCM, obstructive hypertrophic cardiomyopathy. You made reference to the non-obstructive side of it, the ODYSSEY-HCM study. Talk to us about your level of confidence and the potential for that to read out. I think we have some, you know, cross-industry, similar mechanism of action, data points, MAVERICK, et cetera. What does that mosaic lead you know, to s hift your thinking towards the NHCM opportunity and that data?
We're very excited about the NHCM opportunity, Chris, as well as having kicked off the ODYSSEY phase III pivotal study. I think when you think about NHCM, of course, fundamentally in key ways different than OHCM, but obviously phenotypes that share common characteristics. You think about what Camzyos can do to provide some confidence in the NHCM space. I think even more so, when you think about the data that come out of MAVERICK, we touched on a little bit of it and, you know, at the shorter term, when you think about the effects in biomarkers, as well as some of the clinical parameters and subgroups. Small study, I think that's why you have to do the larger phase III study.
On the other hand, when you think about the longer-term data that I just mentioned, it gives us confidence. It's also given us confidence about how we might think about dosing a cardiac myosin inhibitor in NHCM. You get insights when you are able to follow patients for a longer period of time. When we think about NHCM, it's still a condition with high degrees of unmet need. There aren't a lot of options for these patients. You know, it's a progressive disease. In certain cases, patients have to go on for transplant. There can be malignant arrhythmias, so we're very excited about bringing forward Camzyos in the ODYSSEY study. We've just kicked that off this year.
It's proceeding as we anticipated, we're looking to continue to do everything to continue to track to 2025. I've always personally been very fascinated by this therapeutic and this patient class, et cetera. I was practicing critical care medicine in the 1990s at Massachusetts General Hospital and thinking about all the geeky hemodynamic parameters and echocardiograms and this cross current that is creating all this data points. Sort of adoption and utilization, is there something singular that you think is really valuable in terms of getting the lift off on this product and the adoption, the understanding? It feels like it started as a scientific concept. It's going through its adolescence as a business, when does it become kind of like a real franchise?
The way to go to on this thing? It doesn't have the beauty and simplicity of LDL cholesterol, get it to 100. That was basically designed on Madison Avenue. This is more complicated, but what's at the essence? Yeah, that's a fascinating question, Chris. I think when you think about it sort of follows the way I see it, is the data evolution that you've seen in this class. You see parameters, shorter studies, smaller numbers of patients, and you follow biomarkers, you follow echocardiographic parameters. You're not completely sure how they translate, and I mean, that's always the challenge in cardiovascular development, consistencies. You look for consistency across parameters.
Then I think what happens is with EXPLORER, with VALOR, with Camzyos, you see changes in meaningful outcomes, that is, patient outcomes. We're talking about feel and function, things in patients where, again, there aren't options, or the ability to avert really invasive procedures. I think that's really the start, if I understood the question properly, that's the start of showing where the inherent and real benefits to patients for these drugs are. Yes, you continue to follow these geeky biomarkers and echo parameters and all of that, which are critical as you think about it in the long term. You help use that to build your story then in the longer term.
Again, you have to continue to sort of build that foundation. I think having shown outcomes is that start, and I think that's where it all starts and really ends, I think, if we can provide benefits to patients who don't have a lot of options. Finally, for Camzyos, the next frontier is looking at HFpEF, the EMBARK study. Proof of concept, you know, talk about taking this further down the line, ultimately, phase III. Yeah, thanks. We're very excited about the opportunities of cardiac myosin inhibition in heart failure with preserved ejection fraction. It's an area that's hard to develop in, you know, heterogeneous condition. Maybe some phenotypic commonalities, but again, I think, an area where there's a great deal of unmet need, in spite of recent advances.
With the EMBARK study, you know, we gain enthusiasm and confidence based on what we saw in MAVERICK, and we're building on that foundation because there's a lot of commonalities in patients who have HFpEF with those who have the non-obstructive form of HCM. What we're looking for, really simply, is can you dose with a cardiac myosin inhibitor in a safe way, primarily in a smaller phase IIa study, but also see hints of efficacy as well? That's what we're really looking for here. Can you dose it safely and make sure that patients can tolerate cardiac myosin inhibition in those who have HFpEF? You look for, again, as we talked about, signs of improvements in biomarkers. Are we reducing NT-proBNP? Look at echocardiographic parameters.
Are we seeing improvements in filling pressures or volumes? I think most importantly, in a study of this size, you look for consistency across these various parameters because you don't have the duration or the numbers of patients to, of course, look at outcomes in this kind of indication. We're very excited about this. I think it's these data that'll tell us how to develop in the phase IIII space. And ultimately, though, there's excitement, not only because of the mechanism, but because it's complementary, we believe, to the mechanisms that are out there. And ultimately, an opportunity to continue to make a difference in the HFpEF area.
Let's, in the last few minutes, transition over to milvexian, a pipeline asset that candidly got kind of blurry, mixed reviews as we transition here. You're really trying to, you know, achieve something that's a pretty, you know, threading the needle kind of opportunity. Eliquis is, you know, a fine drug. However, obviously we can try to find some opportunity to roam by improving on the safety profile. You outlined opportunities in particular for AFib versus Eliquis, the Librexia trial here. I think most investors at this point, when you talk about milvexian, it's just like, you know, "What do we need to see, and when are we gonna hear it?" What do we need to see, and when are we gonna hear it?
In particular to that one, are there elements of that trial that you think are important for us to know?
Yeah, you know, with Librexia AF, again, you know, you mentioned Eliquis is a great drug, a great advance in this area, there still remains unmet need. Specifically a large proportion of patients still don't get treated or are undertreated for the reasons of real or even perceived risks of bleeding. We're very excited about milvexian as a factor XIa inhibitor, we have kicked off the Librexia AF study. This is a very exciting study, where we're looking to enroll a broad representative patient population of AF, of course, strategically enriched with certain risk factors.
Mm.
You can imagine through, say, CHA₂DS₂-VASc risk factors.
Mm.
That allows us to also look at patients who have increased risks of stroke and bleeding, who have AF. You know, we'll be looking to see, you know, the promise of this class is can you deliver efficacy that's at least as good as a factor Xa, that is Eliquis, but with an improved bleeding profile? What we'll be looking for is improvements in bleeding profile through various indices, and looking for clinically relevant and meaningful differences in bleeding. I think, when you think about it, we've also, with Librexia, tried to develop a study that was simple, easy to enroll
Mm
with criteria that don't rely on a lot of exclusions. For example, were necessary when we developed Eliquis. We'll be looking for that. It's early days. We're tracking according to plan and we're doing everything to bring Milvexian forward to patients as quickly as possible.
Enrollment is on pace with expectations?
Yes.
Okay. The 2026, 2027 timeframe is kind of where we gauzily have the potential read out there. Can you remind me, are there any interims built in so that we might be able to get some sneak previews that could, you know, be very informative?
Yeah. A few things about that, Chris. PCDs, or primary completion dates, you know, across our program
Mm
you know, depending on the study, 2026, 2027, as you referred to. you know, these are event-driven studies, so even those PCDs can be, you know, varied, depending on how the events actually occur, event rates, and how enrollment, of course, occurs. I think, you know, as you know, we don't get into specifics about the interims, timing, or any of those details typically, Chris. What I will say, though, is that we do build optionality into all of our studies, and I'll say we build that optionality in a way that we can read out these studies, you know, in accordance with regulatory
Mm
guidance and such. When you think about this, we'll continue on, we'll continue to progress these studies forward, and you'll hear more about this in the future.
The promised final question on IRA. When most people say IRA and cardiovascular, if you're awake and alert, you're thinking Eliquis.
Fine.
Implications of IRA on cardiovascular development for you, sir?
Yeah, it's actually a little bit. I'm gonna borrow a little bit from Lynelle here. I think when you think about IRA, there is so much uncertainty. There are details that have to come out with IRA, first and foremost. On the other hand, IRA is something as a consideration that we do have to take into account. Certainly, we do in sort of the scope of and context of all these other factors. When you think about IRA inherently, though, it still comes back to, you know, what is the unmet need that we're trying to address? Can we identify areas of great unmet need? And then do we have the molecules and the targets to actually address that unmet need? Milvexian is an example of that.
You know, we do strongly believe that there's unmet need in ACS. We think that there's unmet need in SSP. We think there's unmet need, as we talked about, in AF. That's the reason why we believe, with a confidence in the molecule, that we can develop this in a parallel path, and ultimately, in this case, hopefully, a few years down the road, be able to launch this in rapid sequence. That's one way of addressing that. It'll minimize potentially what we think might come forward with IRA. Again, it still goes back to the science, because it's the belief in these targets, it's the belief in these indications and the unmet need, and trying to bring something forward for it.
Okay, terrific. We're at the close of our session. I always think with the large cap pharmas, getting the opportunity to explore conversations with bench depth, with management teams is so important. The two of you have represented the mothership Bristol very well. Thank you for your helpful comments.
Thank you.
Thank you.