Merck & Co. Aktie

All right. We're going to get started here. Thanks so much for joining us. I'm Terence Flynn, Morgan Stanley's U.S. biopharma analyst. For important disclosures, please see the Morgan Stanley research disclosure website at www.morganstanley.com/researchdisclosures. If you have any questions, please reach out to your Morgan Stanley sales representative. I'm very pleased to be hosting Merck this afternoon. Joining us from the company, we have Rob Davis, the company's Chairman and CEO; and Dean Li, who's Executive Vice President and President of Merck Research Labs. Thank you both so much for taking time on your day to join us. Really appreciate it.

Great. Well, thank you for having us. Appreciate it.

I thought first, I'd turn it over to you, Rob, just to frame the discussion for us, and then we'll launch into Q&A.

Yes. No, I appreciate it, and happy to do it, and good afternoon, everyone. I mean, obviously, already, 2026 has been a very eventful year for us. I would say, and I think it will frame the discussion we'll get into. Our transformation is underway whether it's the product launches we have going, which are all the first waves that are coming all going well. But equally, if not more importantly, the fact that we're getting and seeing continued important data readouts that have all pretty much turned over positive and many at a pace much faster than we expected just gives us a lot of confidence in where we are. We have more to come.

Importantly, while those catalysts have been important, we have more catalysts yet to see this year, both in terms of other data readouts as well as potential filings. So as you look in the near term, a lot of continued excitement and what is ahead of us. And then on top of that business development, what we've done recently with the Terns deal, we'll get into, I'm sure, at some point.

Animal Health. Our Animal Health business is performing at best in industry levels. We continue to have strong confidence in that business that can more than double in the next 10 years on the back of a product portfolio growth, very much in line with what you're seeing on our human health business. And we have the capital -- the resources and the capability to add more. So whether you look at it as launches, as clinical readouts, as business development, I think we're really hitting on all cylinders. So I feel very good about where we are.

More to do. You never say you're done, but I feel very good about where we're standing at the moment. So maybe with that, I'll turn it over if you want to jump in on any of those areas.

Yes, absolutely. I think we'll get through a lot of that. The first I want to start on is just on the policy front. Obviously, you guys are very plugged into D.C., you have the midterms coming up here. But just anything that's on your radar here that we need to be cognizant of?

Yes. Obviously, it's going to be interesting to see how this plays out and what happens in both the House. And interestingly now, the Senate probably is going to be more interesting to watch and even the House. But whether it's Democratic or Republican, however you want to look at it, as an industry group and as Merck, where we're focused, is continuing on what we see as the 2 biggest challenges we continue to have. How do we make drugs more affordable for patients at the pharmacy counter and how do we ensure access to all of these new meds in a world where we have an ecosystem that continues to reward for the innovation we're bringing. And if you look at those assets -- those aspects of affordability and access. Clearly, we continue to believe the challenge is the fact that the innovator, the manufacturer still only gets $0.50 of every dollar. We have to address what happens with all of the $0.50 in the middle. That really is about PBM reform. That's about 340B reform. And I'm happy to say that there's growing momentum. You've seen a lot of movement with legislation in the PBM front.

We continue to think there's more to do there. But importantly, you're seeing movement on the 340B front as well. So we're going to continue in the industry and as Merck to push that. But really with an added emphasis on this notion of access, the fact that you're seeing insurers and PBMs use utilization management to either delay or deny access to new medicines, whether it's through formularies, how they do formulary management through step editing or through prior authorizations.

We think that, that is another element of this broader system that needs to be addressed, and we've spent a lot of time with the members of Congress and the administration trying to bring greater focus on that.

Okay. Great. Maybe the other one on the policy side is just 340B. It's been, I think, front and center for a lot of folks here after second quarter results. So as you think about that going into 2027, how are you thinking about the impact to your business?

Yes. So if you look at 340B, we're very supportive. I think it's important a couple of points. One, as Merck, we very much support the initial and original intentions of what 340B was about, which is how do you support the most vulnerable members of society to ensure they have access to good health care and good hospitals and clinics. The program has been perverted away from that and has grown and morphed in directions that were not in the initial intent, and we need to get back to that original intention. And so as we think about '27, you are seeing momentum, as I mentioned. There is some bipartisan legislation now moving both in the House and the Senate. There's actually, I think, a bill in the House called the Access Act, but maybe also not only from what the legislation's happening from a congressional perspective, you're seeing the administration themselves starting to make movements.

I'd just highlight the fact that we have HRSA running a demonstration project with the Rebate model, which we think is very important. So we're very supportive of all those moves.

As we look at our own business, those will create potential tailwinds if they evolve, but they're not material to us, frankly. It's more of how do we set the right policy environment to get out some of these more fundamental issues that we have in our system.

Okay. Great. The other one you mentioned in your remarks, Rob, is that you guys have had a lot of success on some of the BD deals translating through to positive pipeline wins here. And so I think now you can say like, all right, a lot of these have been ROI positive for the company. And so maybe just what worked? Like what was it that you guys changed when you came into CEO that you think has given you the ability to generate ROI on some of these BD deals. So I think there's this historical perception, again, probably rightly so, where a lot of the legacy deals that maybe you, your peers have done, were being more challenged on the ROI side. So what was it about some of the changes that you guys made on the BD side?

Well, I give all credit to Dean, frankly. My superpower was just listening to Dean. So that -- I think my mom raised me well in that regard. But in seriousness, what we have done is really a lot of people talk about it. I think we've actually tried to both live it and institutionalize it in the way we operate, is treat the pipeline as 1 pipeline, whether it's internal or external, and make sure that we always are trying to look for the best science. We always start with the science. I've never gone to Dean and to our business development folks and said, "Get me an asset in a space." I think that's dangerous because they'll give you the best asset, but that might not be the best asset that's out there. You don't limit them in that way. You can't limit the science, the science has to dictate.

So we always start with the science. But then once we do that, we're willing to look at whether it's an internal asset or an external asset, we evaluate them always the same. We use the same financial measures. We use the same operational rigor. The teams that do the due diligence are our scientists. So it's not like a separate group. When we go into due diligence, it's our scientists on the ground with them.

We leverage our statisticians to be able to make sure that we're understanding the probabilized risks and returns. So it's that model we followed and one of the things we did to organizationally align that is when I became CEO, we moved business development underneath. So all corporate development now sits underneath Dean. And I think that has also allowed for that ecosystem to thrive.

The other thing we do is we have with each of our discovery centers, BD is embedded. So all of our search is done in side-by-side with our scientists. So I think it's that culture, combined with now institutionalizing processes around it that has allowed us to do well. And as I said, it's credit to our scientists. They've made scientific bets based on their expertise. And I think the fact that we have depth of expertise has allowed them to make the right bets.

Okay. Great. Maybe the first one of those I want to talk about is obviously the INT program, which is partnered with Moderna, some recent data there on the Phase III side. So congratulations. Very exciting. I guess, Dean, maybe just help us think about framing what we're hoping to see. I know you can't say ESMO, but again, a conference this fall. And what it would mean for other tumor types because I think that's the question we're all trying to get our head around is not necessarily if the melanoma data is good, not good. We know it's good because it hit at an interim, but what does it mean for other tumor types that you and Moderna are exploring. So can this be a platform, I guess, is the question.

So the first thing is, I think one of the most important pieces of data actually didn't come out in August. They came out in -- during ASCO where we together presented the 5 years from the Phase II. The big concern that I had about this -- I mean the Phase II that was run was robust. But as many people know, there's been a concern that RNA-based, sort of, trying to use that to immunize can be short-lived. And what was really interesting in that data is that we demonstrated that the people who responded who were cancer-free at 1 year remain largely so at 3 years, were largely so at 5 years.

So when people see that data when it comes out at the conference, I think people will immediately see the Phase III and extrapolate to 5, 7, 9 years, and that's a really important point.

The second issue is in that data, there's a small sample size, there's always some imbalance, but what you're hoping in your Phase III is to be in the ballpark of that. And if you are in that ballpark of that, I think it will increase your likelihood of being successful in adjacencies. And what do I mean by adjacencies. We have a relatively conservative plan right now in relationship to INT. We prioritize those tumors that have a high TMB and/or where IO or checkpoint inhibitors have worked and/or where KEYTRUDA itself has laid out in early stage.

So I think the louder the signal comes in for melanoma, I think it will somewhat derisk that relatively conservative plan. What we have not done is we haven't gone in metastatic. We haven't gone in tumors that are not IO sensitive or where a PD-1 works or it doesn't work. And the reason we haven't done it isn't that we think it's a silly idea. We're very glad that other people are doing it. But if that should hit, we will change and expand our program dramatically if that should happen.

The issue for me is to hit and hit fast because this is unlike a T cell engager, unlike a small molecule, unlike an antibody. I think the first-mover advantage here in being able to commercialize in melanoma will teach you -- give you all the repetition that you need, and that in itself will create a lot of information for both Moderna and Merck and give us an advantage. So that's why "we" have a relatively conservative plan scientifically, but the concept is to move fast and to move -- can move fast.

Yes. And so as you think about maybe the next couple of readouts you've got, muscle invasive bladder cancer and RCC, how to think about likelihood of success in those tumor types, where those fall in the spectrum of...

Yes. So they fall in around that conservative plan. You would say that for MIBC or for bladder cancer, the tumor mutation load is higher. But you also have to look at RCC, where RCC, the tumor mutation burden is not that different than MSS CRC. But in RCC, how many immuno-oncology agents work? I mean how many checkpoint inhibitor cytokines work? So I think both of them are good examples but they will give us a general sense of bookends in relationship to our conservative plan, and we will act accordingly as we see that. And we will open other trials depending on what the, sort of -- if MIBC hits it or something like this, we'll start thinking IO, higher tumor mutations; if it's RCC, it's I/O-sensitive, checkpoint sensitive, but a lower TMB.

Okay. Maybe, Rob, one for you. I know you guys had guided to over $70 billion in recent launches pipeline by mid-2030s, and you had a number of different buckets in here, oncology was one of those, looks like over $25 billion. I think from what I remember, INT was fairly minimal in that. And so number one, I guess, am I remembering that correctly? And number two, is it fair to assume that there could be upside now as a result of this new data that we got on a top line basis?

Well, maybe speaking broadly to the $70 billion, and we unpack the comments. But I think, yes, you should assume we see upside to the $70 billion, and I'll give some reasons why. It is specific to how did INT fit. So if you recall, we had $70 billion made up from 20 assets. 10 of those assets, we said, would make up 70% of the $70 billion, and those are the ones that we thought would have readouts really in the next couple of years. We initially expected INT just based on primary completion date, which is what we use as our -- the way we guide was beyond that. It was in 2029. So obviously, pulling it forward to the interim. It was not in the initial 10. It was in the 20. So it is in there.

But if you look at more broadly, what do we see as far as this opportunity. The other thing is not in that $70 billion. The Terns acquisition, the asset -- the TKI, we brought in with that, which we see itself as a multibillion-dollar opportunity. That was not in the $70 billion. Importantly, and this will come up, I'm sure in a moment, MK-2010, which is our PD-1 VEGF, was not in the $70 billion.

And as you know, we are starting multiple studies with MK-2010. So those 2 assets alone are new, they're upsides. And then on top of that, I would say, while we did have INT in there, just given now the fact that we -- if you assume technical regulatory success because that's what we always assume. But then you look at what is the commercial opportunity. I do think it's safe to say that the broad commercial opportunity probably could be bigger now given what we've learned and what we'll continue to see as the data flows out. So all of those things are why we have a lot of confidence that you're going to see us raise that number. We just have to decide when is the right time to do that.

Okay. Is that a this-year event or a next-year event?

Raising the number. To be determined in the near term, I mean, it's coming. Last year, we laid it out at the beginning of the year. We'll think about whether or not probably that would be the timing we think about it.

Okay. Fair enough. Just in the interest of time, I want to keep going here a lot going on. But sac-TMT, another more recent derisking pipeline asset for you guys.

Also it came much earlier than expected.

Okay. Another driver of upside to the $70 billion? What -- but I guess the question is just the one thing that I think we've been getting some questions on is differentiation still versus the competitive landscape. And so I know you guys have a strong view on this. We're going to get some data from AstraZeneca for data from their AVANZAR study, which we haven't seen yet. There were some data for Trodelvy or another TROP2 over the weekend at World Lung. So maybe just level set us on kind of where you see differentiation versus those other TROP-2s given some data over the weekend, but also in the event of the AVANZAR data and what that means for sac-TMT?

Yes. Maybe I'll make some high-level comments, and then Dean can get into the specifics. If you just recall, we have 17 Phase IIIs we're running, 13 of those are in tumor types where we think we'll be first in class. So -- and most of those, they're outside of lung and they're outside of breast. But they are meaningful tumor types. So it's important that and alone, the fact that we can be first-in-class is fairly important. As you look at the more competitive spaces, especially around lung cancer, Dean can get into why we think we have a unique asset. But the one thing I would add to that, that I think is not appreciated is going forward, the number of potential additional combination studies we could think to with sac-TMT, whether it's in combination with MK-2010, which is, as you've seen, is now on clinicaltrials.gov.

Other assets we have is unique because we have such a broad portfolio, we have a lot of different combination assets we can bring. A lot of those studies aren't reflected yet in their studies. We're still -- some are spooling now and more we're continuing to look at. So that in and of itself is something that's underappreciated. And then I think your specific question is, well, what about what differentiates us in the more competitive spaces, and I'll let Dean take that.

Yes. So as Rob said, the linchpin of the whole thing is that we felt the molecule when we looked at the molecule, was different than the previous two. And because it was differentiated, we decided to do 2 things. One is to race the indications where the other 2 weren't trying. We were actually surprised that they didn't move it forward. And you see with the endometrial data, there is a chance that we can be first in lots of these indications that are outside lung and breast and we intend to do that. The other thing that's important about that data is that we had gotten signals in China and when we got signals in China, there's always this question of would you get that signal in a global study. And the endometrial study derisks that to us to some degree.

In relationship to lung and breast, we've already had one that's not going to make it into first line -- one of the competitors. We'll have to see where the second one ends up, but we feel very good based on the Chinese data that this is an important ADC. We intend -- initially, we were very thoughtful of trying to be differentiated. But with the data that we've done with Kelun and with other data, we're extremely confident across PD-L1 that we could play with sac-TMT. The question is when do you play with it with KEYTRUDA and when do you play with it with 2010?

Yes. And when will you guys make that decision? Like what the pieces are you waiting for to make that decision?

Well, those studies are already ongoing. They're on clinicaltrials.gov. And I think moving them from Phase II to Phase III potentially as the data evolves, will happen in the next year, 1.5 years. But they're already actively going in Phase II.

Okay. One other kind of related one from AVANZAR is the biomarker population. And so their data, there's an opportunity for them to show ITT or just a biomarker positive or outright failure. So as you think about that spectrum of outcomes, what does that mean for your sac-TMT program in the event that, let's say, the biomarker population only is positive?

If the situation where their biomarker is only positive, we would look very deeply as to whether or not what our results in a non-biomarker selected would look like. I think the -- that is something that we would gauge, but we'll see as the data advances. And I also think that the other sort of thing is -- we always have biomarkers available for our ADCs, whether we actually use them in the clinical sort of labeling sort of thing is one that's built on what the data suggests.

Okay. Maybe just, again, moving on to another important more recent approval and product for you is enlicitide, and I know there's been a lot of focus on kind of the early launch and access. We've got, I don't know, 5 weeks of prescription data, so I won't ask you to comment on that. But again, just talk to us about maybe the importance of the label and some of the language in there on cardiovascular outcomes. And then what that means for guidelines and then how you guys are thinking about the access equation here, rest of this year into '27?

Yes. And maybe I'll just start with the, kind of, broadly where do we see access and then I'll let Dean speak specifically to the kind of the label and what some of that stuff means. But if you look at the strategy, we've always said we were going to bring. It was we wanted to have an asset that we could price at a competitive price, a low price such that we could democratize care and drive the volume to all the patients that need this.

If you look today in the United States, 30 million people in the United States are on lipid lowering therapies today, not at goal. 30 million people. #1 killer in the United States is cardiovascular disease and impacts from arteriosclerosis is a leading cause. So you have a silent killer that is affecting huge populations of our citizens that have an option to lower their LDL a further up to 60% on this medicine who aren't on it today.

So a lot of the conversation is, well -- and we get this all the time, how are you going to do? Do you think you're going to take share from the existing injectable PCSK9s? Let's be clear, that is not the goal. My goal is not to have 5% of people on PCSK9, which is roughly where it is today. It's to say, how do we get to 50% or more of the population who would be eligible on PCSK9s. Everyone who is on a lipid-lowering agent not at goal should be on -- with an add-on therapy. And we think we are best positioned with the oral LIPFENDRA, which is the brand name that we have.

So knowing that we wanted to make sure we price this in a way that would maximize access. And we've done that. I will tell you what we're hearing from the payer community. They recognize and appreciate the differentiated characteristics of LIPFENDRA, we're actually hearing that. And we have not seen anything other than the ordinary restrictions that you'd see with the new drug.

So I think we've been successful in getting broad access, and we're on a path. As you look forward, we think we'll have full commercial coverage to the majority of lives by the time we get to the end of '27. We expect to have Medicare coverage by 2028. Chance to pull that forward. We're working hard to do that.

So as it sits here today, I feel very good from an access perspective. I think the profile of the drug and to your point, the label is extremely positive and we are very bullish about this, but maybe you can comment on the questions around the CVOT and what the...

Yes. So the bottom line is we have a CVOT proceeding, but I do think the FDA understood that this molecule was designed to do what the antibodies did in relationship to biomarkers. And if you look at the biomarkers of ours, and you look at the antibodies, they, kind of, look like they're all in the ballpark.

I think the second thing that the FDA understood is, although we talk about PCSK9 generally, if you look at, for example, the PCSK9 siRNAs or other sort of things, they're not in the 60% range, although they're in the 50% range. So I thought it was interesting what the FDA did. They reminded people that we don't have an outcomes trial, but they recognize that this drug should be done in addition with a statin. So they say statins have cardiovascular outcomes in our label. And they also reminded everyone that although we don't have cardiovascular outcomes, we were designed to be like an antibody, and they remind everyone that the antibodies have cardiovascular outcomes. So we view that as all positive movement.

And what does that mean for guidelines? Before you have your own CVOT data, is there a chance that you get kind of parity with the antibodies from a guideline perspective? Or do you have to wait for your own CVOT data? Just trying to think through any implications for guidelines.

So if you're talking about AHA/ACC guidelines, I think always, there's going to be some, sort of, question as to -- until you have the cardiovascular outcomes and how do you think through it. But I think the larger question for AHA and ACC is 2 things. The first one is they finally have LDL. The second thing is for those patients who have secondary ASCVD, I think many people believe that their guidelines of less than 70 is not sufficient, it should be less than 55 and 40. I think that's the major issue.

And then the third issue that comes from guidelines is that CMS has never had a quality metric in relationship to LDL, which is shocking. And the question is whether the CMS will begin to do it. That to me is where all of our competitors and us should be pushing for.

And how should we think about the out-of-pocket channel here? I mean, is that a real opportunity? Or is it a function of, look, I mean, most people have commercial Medicare coverage with cardiovascular disease. So it's likely going to be fairly small as we've seen with, kind of, the antibodies? Or is there more of an opportunity for the out-of-pocket channel? And then maybe even step back more broadly, like how are you guys as a company thinking about leveraging an out-of-pocket channel or footprint, given some of the success we've seen for some other companies.

Yes. So I do think the growing acceptance of direct to patient is something to take note of. And I do think you're going to see more of it and it's something that we are looking at doing aggressively not only in the cardiovascular space, but more broadly, it is very asset specific. So not all drugs are -- will meet that space in the right way. KEYTRUDA would never be in that, for example, but there are a lot of opportunities.

And I do think it's an important way to continue to get directly to the patient at prices that often can be cutting out what's in the middle. So we are looking to do that with LIPFENDRA. We are -- we have already announced intentions and we had it as part of our MFN agreement to put this on TrumpRx.gov. We're looking to do that as we move to the back half of this year.

It's -- to that extent, it's immaterial as you think about 2026, and probably, it's going to take some while to ramp, but it is a channel that we are going to take advantage of. And as I said, not only here, but as we bring new assets, it will be something we'll look at each asset and ask because it's something that should also sit in that channel.

Okay. And any -- last one, any early feedback from kind of your sales reps out there in the field? I know you mentioned some of the payer feedback, but anything on the patient side you're hearing from your reps?

The short answer, it's all positive. The amount of press this has received, it frankly exceeded my expectations, the understanding of what we have is probably broader than we thought. So I would say early days, but everything is quite positive.

Okay. Great. Maybe moving on to Tulisokibart, your TL1A antibody for IBD. Maybe just again, any update on when we might see that first set of full Phase III data? Is this something that we could see at the UEGW conference? And then maybe just help us think through that second Phase III trial that you guys have ongoing in terms of timelines for data and anything to call in terms of similarities or differences versus that first data set?

Yes. If I could reframe the question a little bit, which is our interest in Tulisokibart is not IBD. Our interest in Tulisokibart is to be a major node, a major cytokine node across indications. That's why we're doing GI, IBD. That's why we're doing derm like HS. That's why we're doing rheu. And our hope is that this node and this antibody can be one of the best, if not the best biologic in each one of those indications and be one of the safest, if not the safest. Because if we're in that situation for each one of them, that will be great. And in that situation, your comparator changes.

In IBD, you think of IL-23 and HS, you'd think of IL-17AF. So our ambition is broad in relationship to that. Specifically to your question, we need 2 Phase IIIs to be able to file. We should be getting some of that data this fall. I don't know that I will have all the data for any conference this year, but more likely the beginning of next year.

Okay. And then Rob, what does that mean more broadly? Again, if this is a cornerstone for an immunology franchise, again, I've seen some of your peer companies kind of struggle to scale in immunology because of, again, that kind of -- maybe they've got one asset, but maybe it's not like a best-in-class, first-in-class or later, and they don't have enough other assets around it. So how do you think strategically around what TL1A is for the company and your presence in immunology?

Well, I would start by saying we are committed to playing in immunology as an important therapeutic area. And if you look at what we have, both with our TL1A with Tulisokibart, but also what we have, which hasn't been fully disclosed, but in our -- we have a lot in actually our Phase I pipeline moving into Phase II, which as we move over the next year to 2 years, you'll start to see increasing cards turn over. And I think our strategy will become more clear.

But as Dean said, whether it's in rheumatology, whether it's in dermatology, in IBD, we are covering the landscape with the studies we have going. I think the important point you raised is, do you have a drug which is best-in-class, first-in-class? We need to see the clinical data. We need to get the final outcome. If it plays as we hope and we believe it could, and we do have something which is a best-in-class, a new mechanism, as Dean has pointed out, I think that's a different situation from a competitive landscape, it's hard for people to close you out if you have a drug that brings unique characteristics.

So we need to know that. But beyond that, how do we build around it with a portfolio of assets? As I said, many we have internally. We also continue to be open to adding through business development. So this is an area where if we see interesting science, we will move opportunistically because we do think that this is an area we want to be in for the long term.

Okay. Maybe just a couple of quick hits here in the last minutes. One is just on China. I know that has been a source of innovation for you guys, Kelun, LaNova. Again, maybe another asset that I'm missing. But I guess the question we get sometimes is there a risk that either the U.S. government or the Chinese government tries to stop these kind of cross-border deals. I mean what's your take on that?

Yes. I don't want to get -- I don't want to try to speculate on what the U.S. government will or won't do. What I will say is the conversations we're having with Washington is really around respecting and understanding the concerns around national security and making sure that we don't take that lightly, but also recognizing that there's innovation happening in China that should be available. We want to have available -- made available to U.S. patients, to European patients and others. And the real focus needs to be on how do we keep our competitive edge. We are the leader as the United States today. We need to focus on continuing to maintain that. The area where we see the greatest opportunity continues to be in how do we modernize, how we run clinical studies in the United States, primarily as you think about early Phase I first-in-human studies, that's an area where China has a significant advantage in both time and cost.

If you look at the TrialBlazer program being run right now by the FDA, we're very supportive of that. So let's focus on getting the best system in the United States to keep our lead. Let's put guardrails to ensure that we don't trip into national security concerns. And then other than that, let's let the market work and have access to those assets. But to be clear, as Merck, we look at China as an opportunity, but we look globally. We don't source only from China. We source from around the world. There's great science all over the place, including what we're doing in our own discovery. So we're investing in all of those areas to make sure that we have the breadth, regardless of what happens geopolitically.

Yes. Last one is AI. I had to squeeze one in here. Just what's one nonobvious current use case you've seen at the company at any part of the organization?

Yes. I would say I think people assume that we're using AI a lot, you hear a lot of discussion about target identification and this notion of how can I go in silico, find a target and bring it through. We continue to believe you're never going to go straight from a virtual study into humans and ultimately through development, we think that you need the combination of the wet lab with the dry lab, if you will.

But that said, where we have seen meaningful benefits it's, frankly, when we talk about the fact that we're seeing above average PTRS, including especially as we look at our Phase I pipeline, a lot of that is driven by what we have been able to already do with AI, which is how do you think about molecular design and molecular design optimization. And if you can do that early, you can start to get out a lot of the safety issues. You can get to an optimized molecule.

That increases your probabilities it makes it through. It allows you to move faster to get to the optimized target, which brings lower cost. And we actually are benefiting from that and actually are building those savings into our budgets today. So that's something I think is fully -- not fully appreciated is around how you think about molecular design.

Great. Well, I think we're up against time. But Rob, Dean, really appreciate it.

Thank you all.

Thank you.

Great. Thank you for joining us for the afternoon session today. We have team Merck with us. So with us, we have Caroline Litchfield, the CFO of the company. We have Dean Li, the Head of R&D, President of Merck Research and everything. So thank you very much for joining us today.

Thank you for having us.

So I will turn it over to you, Caroline, for all the -- to give us the overview of all the great things you are doing at Merck. And yes, let's just start.

So thank you all for being here today, and thank you for your interest in and support of Merck. Since we were here a year ago, we've made tremendous progress. And that progress is all anchored towards driving our long-term growth ambition. This time last year, we were talking about 20 or so human health products that had the promise of delivering impact to patients and more than $50 billion in non-risk-adjusted revenues by the mid-2030s. At the start of this year, we announced at the JPMorgan conference, we see more than $70 billion of non-risk-adjusted revenue from this suite of human health products. So the transformation of Merck's portfolio is underway.

We've launched several new products. We've seen progress across our clinical book of business, and that's across oncology, cardiometabolic, ophthalmology, immunology, HIV. On top of that, we continue to augment our pipeline with value-creating scientifically focused business development. That includes the acquisitions in this last year of both Cidara and Terns. And we've got an Animal Health business that continues to exhibit strong growth. So we're excited and confident in our future.

And we're going to fully invest behind the opportunities we have with our expansive pipeline and our launches to drive growth into the future. We've got many clinical readouts coming, and I'm sure we'll talk a lot about that. But overall, we are confident in the execution of our strategy, and we're confident in our future. So we look forward now...

Awesome. We are also looking forward to it right now. So last year, we have Eliav here, and I kept asking you what's sac-TMT that you have all these trials going on, what gives you confidence to make such investments. And his response was that we appreciate that you have not seen that what we have seen with Kelun data that are generated in China. Now we are seeing some glimpses of that. So talk a little bit about in last one year or so, what you have learned with sac-TMT and what is still underappreciated for the asset at this point?

Yes. So for sac-TMT itself, you could argue it's the third TROP2 ADC. Whenever you're coming in with a third TROP2 ADC, the minute you say it, they're like, why are you doing? And the concept for us is that we had already seen some data just from preclinical that made us think that this ADC, the linker payload was going to be a cornerstone and would have a different benefit risk ratio, especially in combinations.

The other sort of thing that was really important is that we've had a close relationship with Kelun. And so we trust them implicitly in relationship to how they conduct their trials in China. And the reason why that's important is we almost use it as a reconnaissance force to figure out where we should play. So our initial focus was when we looked at everyone else's TROP2 ADC, we're actually very surprised how focused they were on breast and lung and how not focused they were in other indications. So we put in 17, and 13 of them were not in breast and lung. But we said in breast and lung, we would be thoughtful and we would strike when the time was right.

And what you've seen in the last year is that strategy coming out. Our endometrial is likely to be the first TROP2 ADC, and those 13 trials are moving. But in lung and breast, those data are coming through. You saw in Kelun in China data, in Phase 3 data, very compelling data across the PD-L1 standard. And so I think that gives us great confidence in moving our sac-TMT into lung and being more aggressive about it. You'll probably see data about breast cancer that will allow people to do a comparison. But the other sort of thing is we think the data for sac-TMT is substantially differentiated that not only does it give us an opportunity to be in lung and breast with sac-TMT, but it has us be in a differentiated position to consider things like PD-1, VEGF.

Right. And a lot of us are actually seeing sac-TMT as a replacement for KEYTRUDA, but it does seem like -- it's actually targeted chemo basically. So it could go much further than that. So how do you internally see this asset -- as an asset which like in terms of like just like protecting lung cancer versus like broadening.

Yes. I mean, essentially, our initial strategy was not to protect lung and breast and to go everywhere else because we were -- we were a little bit surprised that other people hadn't done that. And you've seen, let's say, where the growth of KEYTRUDA and other agents have been outside of lung and breast. It's in women's cancer, it's been in those sort of places. So we felt that, that was ideal. More recently, we're now -- the Eye of Sauron is moving back into lung and breast. And that's where we're focused on.

And I think people have asked, are you going to try to do the whole KEYNOTE-189 with sac-TMT? And the bottom line is we intend to go with sac-TMT in the breadth of PD-L1 indications. But one of the things that's available to us is that we believe in many of those indications, we just need to use pembro. But in some of those indications, we may have a unique position to drive a PD-1/VEGF. And so we're being very thoughtful in relationship to that. So it's -- actually, we went outside of lung and breast, and now we're moving back in.

Now it's funny, right? I mean, like this question has moved from why are you running 14 trials to why are you not -- why are you only running 14 trials?

Right. I mean we want to strike when the time is right, and it's to our advantage.

Got it. Completely makes sense. So I mean, you have an event at ESMO as well, you'll see a lot more data there. How far are we from seeing a VEGF/PD-1 plus sac-TMT kind of those combination trials starting at this point?

So I think in the clinical trial side of the government, it becomes very clear to people that we are exploring indications of a PD-1/VEGF with sac-TMT and that we are clearly exploring PD-1, VEGF with WELIREG. And I think people can immediately calculate, okay, there's 50-plus indications for PD-1s and PD-L1s. There's maybe 6 to 7 indications with VEGF. And then of those, the question is, does Merck have a third arm, which truly distinguish that they can go in, in combination. And so what we've said is those 2 agents, our sac-TMT and our WELIREG look different than other people's agents. And so that's a place where we're wondering, hey, can we use it to really amplify what PD-1/VEGF can do.

Got it. Got it. So some of that -- I mean, like I think at ASCO, you talked about it. In due course, you'll have...

Yes. I mean those trials in the clinical trials, I mean, they're posted.

Helpful. Thank you. So going to the strategy side of things and then looking at the -- like -- I mean, like all the success that Dean's group has had in the last 12 to 18 months here and then M&As and all, when you look at the model like 4, 5 years down the line, like how do you see the patent playing out in your internal model? Like is it -- because the -- a few years ago, Rob had this ambitious goal of growing through the LOE. So how close are you to realize this dream?

So our ambition over the last several years has been to diversify within oncology and diversify outside of oncology. And as you've just discussed in oncology, we're feeling very good about the progress we're making with a number of great assets. And similarly, outside of oncology, we feel extremely good. As Rob has described, as we look forward to the LOE period of KEYTRUDA, we do not see a cliff in terms of how revenues may evolve. Instead, we see more of a hill with a quick return to strong growth.

Now that's on a risk-adjusted basis. If we were to look at our own numbers on a non-risk-adjusted basis, the path to growing through the KEYTRUDA LOE is something we continue to aspire to and could become a reality. But the reality is we're not running our business to achieve a certain profile in a single year. What we're doing is we are prosecuting this expansive pipeline in a way to enable us to have sustainable growth into the future, and that remains the priority of our company.

Got it. Very, very helpful. So going back to oncology, so INT. So success we have seen with melanoma, again, I think Phase 2, like it does look like -- I mean, I don't know, data will reveal themselves, but -- with the early success in melanoma, how comfortable should we feel about the other indications you are also pursuing here?

So all in all, even though INT is not a conservative program, the way that we've actually prosecuted is reasonably conservative. We have focused INT where KEYTRUDA works and works in early stage. So that's where we've focused. And then the other place we focus is in a span of tumors that have varying tumor mutation burdens, we've done that. So in the situation with melanoma, it's highly sensitive to IO agents and there's a high tumor mutation burden.

I think that when people see the data, when it gets presented hopefully at a meeting this fall, they will study the Phase 2 and ask how close is this to the Phase 2? Because if you can replicate something close to the Phase 2, which as a sort of oversimplified way of looking at it, what you have is you almost double the number of people who are cancer-free on top of KEYTRUDA. And it isn't like KEYTRUDA doesn't do, it does do something. So that's pretty good.

But the also important sort of thing is you know from a Phase 2 that if you look year 1, year 3, year 5, those people responded, stay responded. So when people see the Phase 3, I think there -- it's not unreasonable to sit there and say, how close is the Phase 2? And they may extrapolate and say, this probably will look like this in Phase -- in 5 years, 7 years, maybe. So I think that will be an important point.

The stronger that data is, it's no different than when KEYTRUDA and OPDIVO came out. The stronger the data was for OPDIVO and KEYTRUDA in melanoma, the more likely you thought it was going to work in lung, which would make it more likely. So I think it wouldn't be unreasonable that if you saw something close to Phase 2 versus not seeing something close to Phase 2. If you saw something close to Phase 2, your pretest probability, at least in some of these IO sensitive and higher tumor mutations, I think many people will calculate in their brain that becomes more likely.

Got it. So like I think you talked about like melanoma is probably more immune -- IO sensitive tumor versus RCC is probably on the other spectrum. In an event that it works in Phase 2 RCC trial, like how big an opportunity does it open up for you?

Well, I think what people will do is they'll consider them as bookend, right? They'll sit there and say, melanoma, okay, RCC is IO sensitive, but it's a lower tumor mutation. So they'll go everywhere between melanoma and RCC and say, okay, non-small cell lung cancer becomes more likely, head and neck becomes more likely. That's how they'll calculate it. They'll sit there and say, well, RCC has around the same tumor mutation as MSS CRC, but MSS CRC doesn't have it.

So I think what someone will do is they'll look at that bookend and they'll do the KEYTRUDA story over and probably probabilize that bookend. And I think that's how people will interpret the data. And to be very honest, that's probably how some of us would interpret the data.

Got it. Makes sense. With all that clinical success, you are creating a good problem for your CFO. In terms of -- like obviously, with the success, you have to invest heavily in the R&D as well, which is the right thing to do. But like -- so this is a question we get from investors a lot that now that the pipeline is really vibrant and growing, you did some deals as well. How -- what are the puts and takes when you think about the guidance for next year? How should we think about expenses and revenues for next year? And I don't want you to give guidance, but obviously, like can you help us understand that?

So we're not giving guidance at this stage, but to give some themes as we look at our business in 2027. 2027 will be another year of investment for our company because we will, as we've noted, invest in this expansive pipeline, and we will invest in our launches so that we are successful in the marketplace. As you look at the P&L, on the top line, we would expect modest growth. We'll have increasing contributions coming from our launch products. They will be partially offset by some headwinds we anticipate on products that face generic competition or will face generic competition.

Notably, we have BRIDION, we have JANUVIA, and we have Adempas that loses LOE at the end of this year. KEYTRUDA remains such an important product for our company for the world, but growth is slowing, as you would expect, given its current phase in its life cycle. We are looking for some pricing pressures in the world, specifically in Germany, where we've seen some policy changes that will impact, I think, growth for KEYTRUDA next year. And we expect our Animal Health business to continue to have strong growth.

As we look at gross margin, we're expecting some improvement in gross margin as there's the roll-off of a royalty on KEYTRUDA. From an expense perspective, as you rightly note, we are in a fortunate position that in a disciplined way, we will invest fully behind our business. And we would expect our investments to grow at a similar rate as what we've seen in 2026 when you normalize for any of the BD upfront or the funding we received for sac-TMT. So we're expecting expense growth of around mid- to high single digit. And then the only other line to call out would be on other income expense. We'll see interest expense tick up a little given the debt that we issued during this year for the business development that we've done. But in summary, a year of modest top line growth, driving expenses to support our pipeline to enable long-term growth for our company.

Very helpful. Thank you very much for that. So now I want to move beyond oncology because you have a lot going on beyond oncology as well. Maybe starting with the EyeBio asset. I mean, you'll have data this year in one of the trials. So the question here is, it's a trial, non-inferiority trial versus Lucentis; however, does -- do you internally believe that you have potential to demonstrate superiority there? Because the argument is that you are going after the weakest drug there, but a little bit refractory setting. So you're going after a different market there. How should we think about -- how did you think about the commercial opportunity when you designed the trial?

Yes. So we had the fortunate concept that when we're designing the trial for MK-3000. We also know that we have MK-8748. So the 2 of them together, although we're prosecuting each one independently, makes us think about the field a little bit differently. So all the anti-VEGFs, whether you go from Lucentis to EYLEA to Vabysmo, they've all been non-inferior trials, right? And so what we're hoping is with 8748, which is not MK-3000, but it's an anti-VEGF/Tie2 agonist. We are hoping that, that one will be a best-in-class anti-VEGF.

So that to us is like going right down in the belly of the beast and saying, of all of these molecules, this one will be the best. In relationship to this Wnt agonist, all of the other major medicines have been VEGFs. There haven't been an anti -- another sort of non-anti-VEGF. And people recognize and ophthalmologists recognize that anti-VEGF is really important, but anywhere between 30% to 40% of people don't respond or stop responding. So what we wanted to do is create an option for them. So all of a sudden, they have 2 hands to fight. They have the best anti-VEGF and they have the first non-VEGF pathway.

And we believe that in true practice, what will happen is ophthalmologists will begin to mix and match them on their own. So for us, it was just really important to have a really clear signal that if -- right, no one's had a new mechanism of action, and we're hoping that MK-3000, remigromig is that first non-VEGF pathway. And if we can do that and also come up with 8748, I think we could really create a situation where ophthalmologists will think about their field for diabetic macular edema and for neovascular AMD, 2 of the major places very differently with both agents in their hands.

Is there a reason to believe Wnt would also work in AMD?

I think you would say that there is a chance that Wnt would be it, and it's more from the anti-VEGF sort of field. In general, things that have worked in neovascular AMD have worked in DME and DME and neovascular AMD. I think for 8748, you've been very, very strong because there's so much precedent. What people would push back is, well, that's great. You have a new mechanism of action, prove it to me. So the issue is that whenever you have a new mechanism of action, I do think that you have a high standard to convince people, and it behooves us to prove that to people.

Makes sense. So with the Tie2, the data on OCT and [indiscernible], they are pretty strong actually compared to anti-VEGFs as well. So how do you envision like this playing out? Like -- is that the reason you believe it is probably the best in trial? Like what gives you...

Well, you just see the different VEGFs and you see Vabysmo, right? Vabysmo is essentially noninferiority, but there's a sense that it dry the eye faster. We're hoping that whatever that spot number is, we're -- ambition is to be superior to it. And that's what that data suggests. And it's not how dry it is, it's how fast, right? What the ophthalmologists, they want to dry you out fast because it's that wet, dry, wet, dry, that thing, that's what disrupts things. So it will be how dry we can get them, but also how fast we can get them. And so when you look at this, the OCT is how they start thinking about it. So for them, OCT is not just a biomarker, it's how they actually think about treating. They actually use that number.

Yes. I mean they treat based -- on the basis...

That's what they treat. It's -- we may talk about heme malignancy. Heme malignancy starts talking about MMR and DMR, right, in some of our trials. People will treat to that number. People are beginning to treat in practice to OCT. So we think that is an important readout.

Very helpful. Moving to TL1A. So I mean, congrats on the success of ulcerative colitis trial. how -- so there are 2 schools of thoughts there. Like one is that TL1A, it doesn't have to be superior. It like -- it doesn't have to be numerically better than IL-23 or anything because it is super clean drug. This has a place, and it's a new mechanism of action, so it should have a place. And then there's the other one because like with IL-23, AbbVie and all these guys are going into combinations and all. So maybe the bar to move into first line will be higher, so it becomes a second-line drug or combination will be important. How do you envision the market in the next 4, 5 years?

So I would separate the different places, right? So in our mind, we're trying to make TL1A a really important node. Other important nodes are TNF and IL-23 and IL-17 and they dominate in different indications. So we'll have to sort of play this out. I think for GI, which is ulcerative colitis and Crohn's disease, I think people start thinking of drugs like IL-23 is -- they're highly effective and they're reasonably safe.

I think some people start talking about other mechanisms like integrins that some people believe are maybe not as effective as the IL-23s, but they're extremely tolerable. So people stay on. Our ambition for whether we're talking about GI or Derm or Rheum is that among the biologics, we are the best, if not the best, but we are the safest as well. And that in each different indication will be important. And it will also be important because it gives us a degree of flexibility because if you have one of the most effective, if not the most effective and you're extremely safe, should you do a combination strategy, you're in a very good position than if you don't have that profile. So that's the profile we're looking, whether it be GI, whether it be derm, whether it be rheum.

Got it. Very helpful. Another question I have is the asset, which is -- which I know you have -- you have an expertise in PCSK9, oral PCSK9 here. So Amgen, Regeneron, they all try to get into primary care market and statin is pretty much a primary care market right now. So to get into that segment, so this is an oral, so primary care should be using it, but how important it is to have an outcome data, not only in secondary prevention, but Amgen now has data with the VESALIUS trial in primary prevention as well. And you've got a really good label actually there. So talk a little bit about like how do you make inroads into that market?

So I'll have Caroline talk about the commercial push and pull. I'll talk scientifically from it. So just to be really clear, not all PCSK9s are the same. The antibodies, I think, in general, people think of LDL-cholesterol lowering of 60%. If you look at the siRNA or other things that affected PCSK9, I think the number is more in the 50%. So not all PCSK9 is the same. I think the field and the FDA was very clear. They understood that this was designed to do something very similar to the antibody.

And essentially, it was designed with the concept of can I do the same thing that a biologic does, but do it in a pill. And what people saw from the biomarker data, which is LDL and ApoB and this, the profile looks surprisingly similar in a biomarker sense to the antibodies. We still need to do the outcome trial, but I think many people in the field sit there and go, okay, this was designed to interdict PCSK9 LDL like the antibodies. It gives you a biomarker profile that looks similar.

They're going to have to do the outcomes trial. But I think the FDA recognized it and you saw how they recognized it because they didn't make any comment in terms of not having cardiovascular outcomes in the label. What they emphasized is this should be as an add-on in statins, and they reminded everyone that statins has outcomes trial, and they also reminded everyone that the monoclonal antibodies, which this was designed to mirror was also in the label. But we do have to do the outcomes because we have to prove that. But I think for many cardiologists and many people seeing the profile of the LDL and knowing the history of PCSK9, I think many people will be very comfortable prescribing it, especially if it's extremely accessible. And then from commercial, I'll have you speak about that.

So we're very excited about the opportunity we have to bring an oral PCSK9 to really address this epidemic that exists. What we have with LIPFENDRA is we're entering a market that now has guidelines in place after many years where those guidelines did not exist on treating to a target level of LDL. And so those guidelines will really help unlock some of the inertia that exists in this marketplace. In the U.S., there's 30 million people who are taking statins who are not at goal.

About half of those are secondary prevention, about half are primary. And we think initially, we expect utilization to be more in that secondary group, those who have established ASCVD. We're getting really strong feedback at this stage from those who have seen the data, understand the data, understand the accessibility of this oral product and see the pricing strategy that we've had as a company. And initial scripts are looking good. So our confidence in LIPFENDRA and its ability to be multibillion dollars in peak revenue is high. We're working hard to break that inertia, and we expect to see good uptake ahead of the CVOT study.

We did the survey, primary care doctors really like it actually. So that will be interesting.

Maybe this is too personal. I actually tested the system because I had a non-cardiologist write me a prescription. I got it.

That's interesting. Awesome. Thank you for that. So the last asset on pipeline side, I want to talk about is CD388. So I mean now you're running the -- like 2 seasons in Northern Hemisphere, 1 season in Southern Hemisphere. Just like I think -- just walk us through like any change in conviction and confidence in the trial so far? And it does seem like you do see Europe also as a market now opportunity as well. So talk a little bit about how your thought process has evolved since you bought [ Cidara? ]

To be honest, it hasn't really evolved that much. The critical piece of information for me is the way that you give this medicine, so it's essentially an antibody drug conjugate. That's the simplest way to explain it, where the drug is an antiviral. And the issue that comes up is that you go to your physician and you get 3 jabs. And there was a view that was held throughout the field that you really shouldn't launch it with 3 jabs. You should launch it with 2 jabs because -- at one time, right, you come in, someone gives a leg, leg and then do your bum or something. I mean it's -- so they really thought that 2 was really important.

So the minute that we do this, that means we have to change 3 jabs into 2 jabs. That immediately creates a time of when we can launch. So the concept for me is until that time comes, I'm going to get as much data as possible because it's not just that I get a label. Remember, this is not going to be sold at the price of the influenza vaccine that I just got from the drugstore. It's going to be more expensive. And so the question that comes up is we think that this is a really important product for the U.S. but also with MFN, we can't have a tenfold discount in Europe.

And so we need to find patient populations where we can hold that price in a situation where we have robust subpopulations. For example, it's not just immunosuppressed. If someone has cardiovascular risk is on LIPFENDRA, should they get it. That's the type of data because it's one thing for the label, which is really important, but especially outside of the U.S., how you deal with the HTA agencies will become really important. And the more strain, the more data, the more different subpopulations that we have, whether they're statistically prespecified or not will be important for those situations. So we're not delaying the launch in any way. The minute you decide that you're going to do 3 jabs into 2 jabs, you create this issue. So my concept is let me play it out all the way to the end and get the maximum amount of patients.

Very helpful. There's no Merck discussion without talking about BD. And there was a time last year or so, like we were waking up every Monday waiting for a press release to hit Merck bought something. So you have been very active, and it shows in pipeline now. Now where you sit right now, how do you think about, one, the need for BD? Number two, if you do see it, like how do you think about what would be the asset? What kind of asset or profile of asset would you be interested in?

We're proud of the BD that we've done thus far. We've brought some great assets into our company that have the opportunity to advance patient care and drive growth for our company in future. As we look forward, that strategy is unchanged. We will continue to look for the best science externally that when brought into Merck that will create value, address areas of unmet need and drive growth for the company. We're not desperate to do any deal, but we will continue to do the right types of deals for our company.

What we've talked about in the past, and that's consistent today is a sweet spot has been deals that are in the $1 billion to $15 billion range. And we've also talked about as we look at areas of unmet need, that including oncology, including cardiometabolic, but we also see immunology as an opportunity space. So BD will remain an area of focus for any cash that we have at our disposal but science-led to drive patient impact and growth.

Dean, anything to add?

Whatever money she has, I know how to use it.

Thank you very much. On that high note, I really appreciate you joining us today. Thank you.

Thank you for standing by. Welcome to Merck & Company, Inc. Rahway New Jersey USA Second Quarter Sales and Earnings Conference Call. [Operator Instructions] This call is being recorded. If you have any objections, you may disconnect at this time.

I would now like to turn the call over to Mr. Peter Dannenbaum, Senior Vice President, Investor Relations. Sir, you may begin.

Thank you, Shirley, and good morning, everyone. Welcome to the Second Quarter 2026 Conference Call for Merck & Company Inc. Rodway New Jersey USA. Speaking on today's call will be Rob Davis, Chairman and Chief Executive Officer; Caroline Litchfield, Chief Financial Officer; and Dr. Dean Li, President of Research Labs.

Before we get started, I'd like to point out that we have items in our GAAP results such as acquisition-related charges, restructuring costs and other items that we have excluded from our non-GAAP results. There is a reconciliation in our press release. I will also remind you that some of the statements that we make today may be considered forward-looking statements within the meaning of the safe harbor provision of the U.S. Private Securities Litigation Reform Act of 1995.

Such statements are made based on the current beliefs of our company's management and are subject to significant risks and uncertainties. If our underlying assumptions prove inaccurate or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

Our SEC filings, including Item 1A and the 2025 10-K, identify certain risk factors and cautionary statements that could cause the company's actual results to differ materially from those projected in any of our forward-looking statements made this morning. Merck & Company Incorporated Rahway, New Jersey, USA, undertakes no obligation to publicly update any forward-looking statements.

During today's call, a slide presentation will accompany our speakers' prepared remarks. These slides, along with the earnings release, today's prepared remarks and our SEC filings are all posted to the Investor Relations section of our company's website. With that, I'd like to turn the call over to Rob.

Thank you, Peter. Good morning, and thank you for joining today's call. I remain very pleased with the substantial progress we're making across our business, driven by strong execution, growing contributions from new product launches and the continued advancement of the next wave of innovation from our pipeline.

Earlier this year, we provided insight into greater than $70 billion of commercial opportunity we have from over 20 new products that we expect will transform our portfolio and, in many cases, the practice of medicine as well as fuel growth well into the next decade. We also outlined a series of clinical milestones that represent key events to substantially derisk this opportunity.

Since then, we've made meaningful advancements against that objective, including several important proof points that have occurred over than expected. This progress further bolsters my high confidence in the future of our company and our ability to create long-term value for patients and shareholders.

Turning to our second quarter results. We delivered revenue of $16.6 billion, reflecting continued strength across Oncology and Animal Health as well as increasing contributions from our recent launches. Importantly, while we're delivering for patients today, we're also making substantial investments in the next generation of innovative medicines and vaccines. We remain confident in our outlook for the remainder of the year, which Caroline will discuss in more detail in a moment.

We also achieved several important clinical and regulatory milestones. In cardiometabolic, the FDA approved LIPFENDRA, the first and only oral PCSK9 inhibitor to help reduce LDL cholesterol in adults with hypercholesterolemia along with diet and exercise. We're pleased to have worked with the FDA through the Commissioner's national priority voucher process to bring this important new treatment option to patients on an accelerated basis. We look forward to providing broad access for patients to help address elevated LDL-C a major modifiable risk factor for cardiovascular disease.

In Oncology, we received several approvals that underscore the ongoing impact of KEYTRUDA and the enduring strength of our oncology portfolio. At ASCO, we presented encouraging data that further demonstrate the durability of KEYTRUDA and at our investor event, we highlighted advances for a number of promising candidates across our pipeline. This included the first positive top line results from our expansive Phase III global clinical development program for sac-TMT, our TROP2-directed antibody-drug conjugate in certain patients with advanced or recurrent endometrial cancer.

In Immunology, we announced positive Phase III top line induction results for tulisokibart. For certain patients with ulcerative colitis and are starting to see the first of numerous additional trial readouts, reinforcing our confidence in the potential of this program. And at the age 2026 Congress last week, we shared compelling data from our broad HIV pipeline, including firslatrivir in combination with lenacapavir, which has the potential to be the first oral once-weekly HIV treatment for virologically suppressed adults.

We are excited to be returning to the HIV field with an array of important therapies, including the recent launch of Envinzo. Ahead of the meeting, we also announced initial access plans for alomotrivir, our investigational once-monthly oral HIV prep candidate now in Phase III studies, underscoring our commitment to help enable broad and sustainable access to this candidate upon its potential approval. We also continue to augment our portfolio through disciplined business development.

During the quarter, we completed the acquisition of Turns Pharmaceuticals, adding MK-4208 and a novel, potentially best-in-class therapy for certain patients with chronic myeloid leukemia. This transaction strengthens our hematology pipeline adds another promising late-stage growth opportunity and reflects our continued focus on pursuing science-driven business development that can benefit patients and enhance long-term shareholder value.

This quarter marks my fifth year as CEO. And as I reflect on the commitments our leadership team made in 2021, our strategy was clear: maximize the transformative potential of KEYTRUDA expand, deepen and extend our leadership in Oncology, bring forward new growth drivers across additional therapeutic areas and advance Merck's mission of using the power of leading-edge science to save and improve lives around the world.

Today, I'm proud that we are successfully executing on that strategy. Each year, we're making important progress in building a stronger foundation for our future. We're broadening and diversifying our pipeline. Advancing multiple potential blockbuster opportunities and achieving clinical, regulatory and commercial milestones that will benefit patients and enhance our long-term growth trajectory.

I believe Merck is substantially stronger, more diversified and better positioned for sustainable growth than it was just 5 years ago. While more work remains, I'm increasingly confident in Merck's future, particularly with the rapid pace of clinical and regulatory events now occurring. This confidence is grounded in the strength of our science, our disciplined approach to capital allocation, including business development, and the dedication of our colleagues around the world who work every day to deliver for patients.

I want to extend a special word of thanks to our global team for this substantial progress and for their commitment and execution on behalf of patients, shareholders, and all of our stakeholders. And now I'll turn the call over to Caroline.

Thank you, Rob. Good morning. We delivered growth in the quarter, led by continued strength in Oncology and Animal Health along with increasing contributions from our diverse and compelling new products across an array of therapeutic areas. Our strong commercial and operational execution continues to drive near-term performance while we invest in our outstanding pipeline to create long-term value for patients, customers and shareholders.

Now turning to our second quarter results. Total company revenues were $16.6 billion, an increase of 5% or 4% excluding the impact of foreign exchange. The following revenue comments will be on an ex exchange basis. In oncology, sales of the KEYTRUDA family of products which includes KEYTRUDA and KEYTRUDA QLEX, increased 4% to $8.4 billion, with global growth driven by strong uptake in earlier-stage cancers and continued robust demand from metastatic indications.

Strong utilization in tumors that primarily affect women, including breast and cervical cancers, and increased use of KEYTRUDA in combination with Padcev in locally advanced or metastatic urothelial cancer were key contributors to growth. Sales of KEYTRUDA QLEX were $463 million. We have seen physician and patient adoption increase since the permanent J-code was established in April.

As expected, early use has been predominantly in patients who are either on monotherapy or in combination with an oral agent. We remain confident in the trajectory of KEYTRUDA QLEX adoption. Our broader oncology portfolio delivered another quarter of strong growth. WELIREG sales increased 67% to $271 million, driven by continued uptake from international launches and increased use in certain U.S. patients with previously treated advanced renal cell carcinoma.

We are excited that certain patients with earlier stage renal cell carcinoma may benefit from adjuvant treatment with WELIREG following the recent FDA approval of LKTESPARK022. In vaccines and infectious diseases, GARDASIL sales were $1.2 billion, an increase of 3%. Sales in international markets grew 6% while the U.S. was roughly flat as lower demand and timing of CDC purchases was largely offset by price.

In pneumococcal, CPVAXIVE sales were $184 million an increase of 40%. Growth was primarily driven by uptake from ongoing launches in certain international markets as well as higher demand in the U.S. In HIV, we are pleased to have launched IDVYNSO, our once-daily oral 2-drug single-tablet regimen of dereverine and islatravir for certain virologically suppressed adults.

We have seen encouraging early progress on access and reimbursement and look forward to broadening access over time. In cardiometabolic and respiratory WINREVAIR global sales were $588 million, an increase of 75%, reflecting continued strong demand from adults with pulmonary arterial hypertension.

In the U.S., we saw further progress with more than 1,800 new patients having received a prescription and an increase in the proportion of patients whose background therapies do not include a prostacyclin. Outside the U.S., we continue to progress with ongoing launches. OHTUVAYRE sales were $204 million, reflecting continued prescription demand from patients with COPD and as well as the benefit from the timing of specialty pharmacy purchases.

Our Animal Health business delivered another quarter of solid growth, with sales increasing 5%. Livestock sales grew 6%, driven by higher demand for ruminants and poultry products. Companion animal sales increased 5% due to new product launches. I will now walk you through the remainder of our P&L, and my comments will be on a non-GAAP basis.

Gross margin was 81.1% a decrease of 1.1 percentage points, primarily due to higher inventory reserves. Operating expenses increased to $12.6 billion. There was a $5.7 billion charge for the acquisition of Terns Pharmaceuticals in the quarter compared with a $200 million business development charge a year ago.

Excluding these charges, operating expenses grew 7%, reflecting increased investments in support of our launches as well as our robust early and late phase pipeline partially offset by benefits from our multiyear optimization effort and recognition of a portion of the external funding for sac-TMT development.

Other expense increased to $290 million, primarily reflecting financing costs related to recent business development transactions. Our tax provision was $882 million. As a result of the nontax deductible onetime charge for Terns, our tax rate was 160.3%. Taken together, we reported a loss of $0.13 per share, which includes a onetime charge of $2.31 per share from the acquisition of Terns.

Now turning to our 2026 non-GAAP guidance. We have raised and narrowed our full year revenue guidance range to be between $66.3 billion and $67.3 billion representing growth of 2% to 4%, including a positive impact from foreign exchange of approximately 1 percentage point using mid-July rates.

Gross margin is now assumed to be approximately 81%, reflecting higher inventory reserves. Operating expenses are expected to be between $42 billion and $42.7 billion, -- this range includes $5.8 billion for the upfront charge for terms and investment to advance MK-4208. This guidance does not assume additional significant potential business development transactions.

Other expense, which now includes the financing costs for Terns is expected to be approximately $1.4 billion. We now expect a full year tax rate between 35% and 36%, which reflects the nontax deductible onetime charge for Terns. We assume approximately 2.48 billion shares outstanding. Taken together, we expect EPS of $2.66 to $2.76 with a midpoint of $2.71, including a positive impact from foreign exchange of approximately $0.15 using mid-July rates.

This range also includes an upfront charge of $2.31 per share related to the acquisition of Terns as well as approximately $0.12 per share of ongoing costs to advance MK-4208 and finance the transaction. As you consider your models, there are a few items to keep in mind for the second half of the year.

First, for OHTUVAYRE. We remain excited about OHTUVAYRE's strong clinical profile and look forward to achieving its multibillion-dollar commercial potential in the coming years. Third quarter sales will be impacted by the unwind of specialty pharmacy purchases in the second quarter. We continue to invest behind our sales force and promotion to reach more physicians and patients in the U.S. We are also working with our specialty pharmacies to improve patient experience. We expect these actions to lead to accelerated growth in 2027.

Next, we anticipate that total U.S. KEYTRUDA year-over-year growth will moderate as we increasingly reach peak penetration across several key indications. Additionally, as a reminder, we benefited by approximately $250 million due to the timing of wholesaler purchases in the third quarter of 2025, which will not repeat this year.

For BRIDION, U.S. sales are anticipated to decline at a slower pace than previously expected due to lower-than-anticipated generic competition. Finally, other revenue in the second half of 2026 is expected to be significantly higher than the second half of 2025. This increase is primarily due to our revenue hedging program as well as an expected milestone receipt in the fourth quarter related to an out-license agreement.

Now turning to capital allocation, where our strategy remains unchanged. We will continue to prioritize investments that support near- and long-term growth including our new product launches and robust pipeline. We remain committed to the dividend with the goal of increasing it over time. Business development remains a high priority, and we maintain the ability within a strong investment-grade credit rating to pursue additional science-driven value-creating transactions.

We are on pace for approximately $3 billion in share repurchases this year, as previously communicated. To conclude, as we enter the second half of the year, we remain confident in the outlook of our business, supported by global demand for our innovative medicines and vaccines, including our many new product launches. The transformation of our portfolio is underway and we are well positioned to deliver value for patients, customers and shareholders now and into the future.

With that, I'd like to turn the call over to Dean.

Thank you, Caroline. Good morning, everyone. The second quarter was marked by several important regulatory and clinical milestones. Today, I will provide updates in cardiometabolic disease, HIV and infectious disease, immunology and oncology. I will conclude with key upcoming milestones as we look toward the second half of 2026.

First, in cardiometabolic disease, as Rob mentioned, we recently received FDA approval for LIPFENDRA, the first approved oral PCSK9 inhibitor. In the CORALreef Lipids trial, LIPFENDRA was shown to be highly effective in lowering LDL cholesterol with up to a 60% reduction when added to a statin.

Earlier this year, updated U.S. guidelines on the management of dyslipidemia from the American College of Cardiology and American Heart Association recognize that atherosclerotic cardiovascular disease remains the leading cause of morbidity and mortality and underscore the need for earlier intervention to help reduce lifelong risk from prolonged elevated lipoprotein exposure.

Guidelines also reestablished and lowered LDL-cholesterol treatment goals, including to under 55 milligrams per deciliter for individuals with ASCVD who are at very high risk of ASCVD events. The approval of LIPFENDRA is a major milestone in our effort to make PCSK9 inhibition accessible in a convenient daily oral option.

As an oral macrocyclic peptide, LIPFENDRA has the potential to extend the reach of this therapeutic approach globally. Additional regulatory reviews are underway in the European Union and China. We are also advancing combination approaches designed to further reduce LDL cholesterol and target additional ASCVD risk factors. Studies are ongoing to support the development of 2 potential fixed-dose combinations anchored by LIPFENDRA, 1 with rosuvastatin and another with MK-7262 our oral LP(a) inhibitor.

Turning to HIV. Yesterday, we hosted an investor event focused on our HIV program, including new data presented at AIDS 2026. IDVYNSO provides the foundation of what we believe will be a series of novel entries into the field. Our late-stage pipeline aims to address unmet needs for those living with or at risk of HIV through innovative oral options, including 2 once-weekly treatment regimens and a monthly oral option for pre-exposure prophylaxis.

In collaboration with Gilead, we announced full results of the Phase III ISLEND-1 and 2 trials evaluating the investigational oral once-weekly regimen of islatravir and Gilead's lenacapavir both studies demonstrated maintenance of virologic suppression and adults living with HIV who switched to therapy from a daily standard of care.

These results support the potential for Isle to become the first approved oral once-weekly treatment regimen for adults with virologically suppressed HIV. Results were also presented from a Phase IIb study evaluating the investigational oral once-weekly combination of islatravir and ulonivirine an internally developed investigational non-nucleoside reverse transcriptase inhibitor in adults with virologically suppressed HIV.

Based on these results, we plan to advance ISO/ULO into Phase III studies for people living with HIV who are previously untreated and those with prior treatment experience. We also continue to evaluate our monthly oral HIV prep option, alematrivir in 2 Phase III studies anticipated to read out next year. Next, in infectious disease. We are progressing our Phase III study of MK-1406, an investigational long-acting strain agnostic antiviral designed to prevent influenza.

Enrollment was completed in the Southern Hemisphere. Plans are now in place to continue the study through a second northern hemisphere flu season to strengthen our global regulatory submissions. We remain on track for potential approval in 2029. Moving to immunology to lesocabart became the first anti-TL1a monoclonal antibody to demonstrate positive results in a Phase III trial.

In June, we reported on the induction only study of the ATLAS-UC trial in patients with moderately to severely active ulcerative colitis, tulisokibart met the primary endpoint of clinical remission as well as key secondary endpoint with no new safety concerns identified. We look forward to the upcoming readout of the larger induction and maintenance study, which together with the induction only study would form the basis of a regulatory filing and will be presented at an upcoming scientific congress.

These findings reinforce the potential of targeting TL1A to help address immunofibrosis, a key driver of disease progression across multiple immune-mediated inflammatory conditions. We have advanced a broad Phase II development program to further explore this hypothesis and now have results from 2 of these studies.

In SSc-ILD, the study did not meet its primary end point. In hidradenitis suppurativa, we are pleased to share that the study met its primary and key secondary endpoints. Results will be shared in due course. Finally, in oncology, KEYTRUDA continues to generate compelling clinical data and regulatory approvals, including in earlier stages of disease.

Recently, building on the approval of KEYNOTE-905, the FDA approved an expanded indication for KEYTRUDA and KEYTRUDA QLEX, each with pets as treatment before and after surgery for adults with muscle invasive bladder cancer based on the data from KEYNOTE-B15, this regimen is now improved regardless of cisplatin eligibility and is the first and only perioperative immunotherapy plus ADC regimen to extend survival for these patients.

We are also pleased that the FDA recently approved KEYTRUDA and KEYTRUDA QLEX in combination with WELIREG for the adjuvant treatment of certain patients with clear cell renal cell carcinoma based on the LITESPARK-022 study. This marks WELIREG's first approval in earlier-stage disease and brings the total number of earlier-stage indications for KEYTRUDA-based regimens to 13.

In June, at our ASCO investor event we shared updates across our broad and diverse oncology portfolio. We also highlighted a series of pivotal readouts expected over the next several years. We are now beginning to see the first of those milestones materialize with the announcement of positive Phase III results from our global profuse development program evaluating sac-TMT.

In TroFuse-005, sac-TMT demonstrated statistically significant and clinically meaningful improvement in both overall survival and progression-free survival versus chemotherapy in certain patients with advanced or recurrent endometrial cancer. We plan to apply the National Priority Review Voucher for sac-TMT towards our filing in endometrial cancer.

These results represent the first readout from our global TroFuse program which includes 17 Phase III studies. The TroFuse program was intentionally designed to pursue both first-mover opportunities where sac-TMT can establish early leadership and indications in breast and non-small cell lung cancer where we can apply novel development approaches. This global effort continues to be informed by promising results generated by our partner, Kelun from their program evaluating sac-TMT in China.

Positive results from the OptiTROP-Lung05 and more recently, OptiTROP-Lung06 further strengthens our confidence in the potential of this differentiated TROP2-directed ADC. In closing, we anticipate a busy second half of the year. with multiple events and milestones, including in cardiometabolic and respiratory, the September 21 PDUFA date for WINREVAIR for the label update based on the Phase III HYPERION study, in immunology for tulisocobart, the second readout from the ATLAS-UC trial and the presentation of data from the Phase II HS study.

In ophthalmology, data from the Phase III BRUNELLO study of remigromig also known as MK-3000, our novel wind agonist being evaluated in patients with diabetic macular edema. And finally, in oncology, potential approvals for WELIREG plus LENVIMA in advanced renal cell carcinoma and for IDXD in extensive stage small cell lung cancer and data presentations from across our broad oncology portfolio, including detailed results of the Phase III Tropuse-005 study. Please mark your calendars for the evening of Monday, October 26, and where we will host an investor event at the European Society for Medical Oncology in Madrid.

I look forward to providing further updates on our progress. And now I will turn the call back to Peter.

Thank you, Dean. Shirley, we're now ready to begin Q&A. And we kindly request that analysts limit themselves to 1 question today so we can get to as many questioners in the time that we have. Thank you. .

[Operator Instructions] First question comes from Akash Tiwari with Jefferies.

Dean, you any stated a biomarker strategy would be the right approach for first-line -- but with sac-TMT, we've seen a signal regardless of PD-L1 expression with the Optitroph105 and 06 data, what are the chances we could see a broad sac-TMT pembro trial that goes head-to-head against KEYNOTE-189 and is it fair to say we could see SAC TMT combos with both pembro and a PD-1 VEGF for first-line lung?

My simple answer is yes on all accounts, but I'll just step back a little bit, which is for a -- sac-TMT we've stated, we think it's a cornerstone ADC. I mean it's a TROP-2 ADC, but it has a novel linker and payload. And as described in the prepared remarks, we've sort of split the Phase III into 1st mover where we go into indications where we thought we could be first. And actually, what we're hoping is that the shops 005 and endometrial sort of gives validation to that strategy.

And as we've noted, we've talked to the administration's FDA, and this will be the 1 that goes for national priority vouchers. In breast and lung, we've said that we need to be differentiated given other TROP-2 ADCs. But as you point out, the Keen Optiro lung 006 gives us a lot of confidence in the target and to target it across the full spectrum of PD-L1 -- so yes, we are going to rethink KEYNOTE-189, which is KEYTRUDA plus chemo, and now we have a TMT as an ADC as a next-gen chemo.

I do think that we're going to be very thoughtful as to the IO agent and when we should use KEYTRUDA and when we should use other agents such as MK-2010, and -- and as you might imagine, we're advancing MK-2010. With that in mind, we are moving quite fast in relationship to initiating trials some that are signal finding some that are dose and scheduling to optimize with novel agents, and we're advancing trials that can go from a Phase II to Phase III seamlessly.

Our next question comes from Umer Raffat with Evercore.

Dean, congrats on the HS trial update for the TL1A, I'm just trying to think out loud to what extent as we go into these new indications, is the activity we're seeing for these TL1As beyond what we would have expected from a TNF. I'm sure you can appreciate where I'm coming from on this?

Yes. Thank you very much. So just to step back a little bit. I think the question is posed and the fact that TL1A is a member of the TNF superfamily, the TNFs have been really important drugs. They have been advanced. There is often problems with combining them because of their safety signal. In relationship to what we've seen so far, clearly, when you think about immunology, you think of 3 buckets, you think of GI, you think of derm and you think of rheumatology.

In GI, clearly, we're very we're very eager to move forward in ulcerative colitis and Crohn's disease, and we're really eager to see the other half of the UC study. In the derm sort of space, we have it in HS and I think that's important as well as we have psoriatic arthritis. I think the positive readout for HS gives us more confidence in the derm sort of possibilities for this drug.

And so that's where we're looking at. I still think that within the room space, which is, let's say, RA and to some degree, psoriatic arthritis, we'll have to sort of play that out as the data comes out. But I can just tell you, for example, for rheumatoid arthritis, we have very clear biomarker data suggesting we should go after TL1A, and clearly in something like rheumatoid arthritis there are animal models in preclinical where you can estimate what your activity is, and we have that data that gives us the strength to move forward in rheumatoid arthritis.

Our next question comes from Terence Flynn with Morgan Stanley.

Two part for me. I was just wondering, Dean, if you could help us think about ahead of the Astra data of ANSA data, what you'd be most interested to see in that data set and implications your sac-TMT development strategy? And then anything you can say, I know it's a colon study, but OPTOTROPNG-06 just in terms of control arm performance in that trial. Any comments?

Yes. So let me take the last question first. We have a great partner in Kalun. We see very detailed data and we are very comfortable with the data that they've shown us and it gives us great confidence in moving forward. I would just highlight that some of the data that we saw is why we, for example, moved quickly to endometrial. So we have a lot of confidence in how they run their clinical trials and their data. I forgot the first half again.

Avanza.

Avanza. I think the critical thing is, I think the vans are -- I think we're waiting to see what the readout looks like. We're looking to see what it looks like in Alchimers comers, what we look like in relationship to biomarker selected. And that will give us some views as to how do we advance ours, the need for a biomarker. You can always have a biomarker, but that doesn't mean that you always need it.

And then the other sort of thing is how we think about advancing it in relationship to combination with an excellent PD-1 like KEYTRUDA or whether or not we should move it forward with an excellent PD-1 VEGF.

Our next question comes from Michael Yee with UBS.

Great. On TL1A, 2-part question. You had 1 positive Phase III in UC but not a whole lot was said. So how do you think we should think about the profile in ulcerative colitis appreciate in the second studies coming and then it's supposed to be all about fibrosis, but then the SSC study wasn't positive today. So how does that change your thinking around Crohn's and that fibrosis opportunity.

Yes. So thank you very much for that question. In terms of the TulaSocaBar Study 2, I mean we're very eager to see Study 1 because together, that will be the package that we sent to the FDA. And we are looking forward to that readout as we advanced it.

Again, in Crohn's disease, there's a clear signal, not just from us but from others. And it's what do we see in Phase III. So I think we're very interested in moving those forward. You can look at some of the derm in the room indications that I spoke about. They will also have fibrosis component. In relationship to SSC ILD. I would just step back. I don't know any anti-cytokine that has worked. So this was a bold move to move that forward. It's a challenging and refractory disease. We see no safety concerns. But I will tell you that when we publish that data as you might imagine, we will.

I look very carefully at the placebo arm. If I see no progression in the placebo arm, it is an SSE IOD, but if I have no progression in the placebo arm, the chances that I will be able to show benefit in a treatment arm becomes much more difficult. So I would not throw out the immuno fibrosis based on the SSE IOD study not reading out positive in the specific patient population we recruited.

Our next question comes from Geoff Meacham with Citi. .

Dean, on the friend launch, I wanted to ask how you guys view the pace of maybe initial access. I wasn't sure what the right reimbursement expectation or if you thought the outcomes trial maybe would be more needed as a commercial tipping point.

So why don't I turn the commercial to Rob, if that's okay? And then I can answer the remaining questions from a scientific standpoint.

Yes. Great. Thanks for the question, Jeff. If you look at it overall, I would just say we're very pleased with what we're seeing so far. Obviously, you saw the label. We have a very clean label, 1 we feel very good about. And with the fact that we have up to 60% LDL lowering, I think this is going to be a meaningful treatment. We're seeing very high interest from physicians and patients based on the approval announcement and ordering has begun last week, and we expect to be able to have it to pharmacies here shortly.

As we look at it from an access perspective, overall, we're, I think, in pretty good shape. You remember, we really tried to set this up for broad access in the way we priced it and the way we're going. That said, we do believe it's going to take time to get that access established. So we are expecting to see the pace not be as fast out of the gate. But with long term, continue to expect to see this to be definitely a blockbuster opportunity as we move forward. I'll let Dean speak specifically to the broader question from a science perspective.

Yes. So 1 of the thing I do want to highlight is there's often a lot of discussion of this FDA or this administration FDA, I can tell you, in our conversations with this administration's FDA, they wanted to use Liffendra as a cornerstone way to demonstrate what they're trying to do with their priority sort of review.

Most of the programs in that priority review only touch one of the sort of the pillars of what they're trying to do. But they were very clear to us they want us to touch all of these pillars. And those pillars is to target public health crisis, an innovative breakthrough, a large unmet need, especially in chronic disease, which is a pillar of this HHS.

They were very clear they want onshoring and supply chain and resilience in the U.S., and they were very interested in accessibility in relationship to increasing accessibility. So those 5 sort of pillars, that's what the FDA and us are racing to do as we launch this important product.

Our next question comes from Chris Schott with JP Morgan.

I guess with the pipeline derisking we've seen over the past year, can get any directional views or updated color on what you're envisioning Merck's earnings profile could look like as we move through the KEYTRUDA LOE? I know the focus of the company is more on the return to growth as we look out into the early 2030s. But just would be any thoughts on that transition period of earnings could look like over that, let's say, 2028 through early 2030s period.

Yes, Chris, thanks for the question. As we've said in the past, we feel very good about the progress we're making with the over 20 products we have coming, $70 billion of commercial opportunity, and we've already started to see meaningful clinical derisking happening at a pace faster than we expected as well as good solid launches from the products that have launched.

So as we sit here today, we feel very good, as I've said in the past, -- we see that as the LOE period is more of a hill than a cliff. Nothing has changed in our view. I do think you're going to see a shallow dip with a fast return back to growth.

And candidly, if we look at it on a non-risk-adjusted basis, we still aspire to grow through it. There still is the potential more to do to achieve it, but we're working to get there. So as I sit here today, I feel very good about where we are and the progress we're making. Always more to do, but I feel good about the hand we have right now.

Our next question comes from Courtney Breen with Bernstein.

Just one on LIPFENDRA, following up on the comments regarding kind of fixed-dose combinations. You highlighted rosuvastatin in your own Lp(a). Particularly with rosuvastatin, I would love to hear a little bit about how you're thinking about which dose you might consider. Is this just for those patients that need further escalation once they've made it to the 40 mg, recognizing there are some more adverse events there?

And then secondarily, are you looking at kind of continuing other combinations. We've heard GLP-1 combinations with the PCSK9s from peers and wanted to understand if you're still advancing or considering this opportunity. Finally, we haven't seen it yet pop up on Tronox. Just wondering kind of when we can expect that access channel to begin to become available?

Why don't I let the TrumpRx go to Rob and then I'll take the rest of them?

Yes, we're excited about the opportunity. And as you know, in our MF agreement, we did commit to putting Lifendra on Trump Rx. Those plans are underway. We're working on obviously getting the initial launch moving -- and as soon as we get that going, we'll get it on TrumpRx. So more to come on timing there.

Yes. In relationship to your combination question, thank you very much. I mean right now, we have an oral PCSK9 that was designed based on the learnings of the antibodies, and we have been able to achieve up to 60% reduction in LDL cholesterol. We are hoping that with rosuvastatin, we would provide to be all the doses. But that combination, we think that we could get up to 80%.

I mean, if we could get up to 80% in a combination, that's a good day for medicine. So those are the sort of way that we think about the rosuvstatin for the LP liter way, we'll have to see what the LP(a) actually does in relationship to the reduction -- but we are hoping that in a patient who has high LPA that our combination will be able to give unprecedented CVOT outcomes in relationship to that.

In relationship to GLP, we have focused and said that we're focused on oral combinations. And there is clearly the ability to combine GLP and PCSK9. One of the things that we are very thoughtful about is that for the GLPs, you kind of do the step-up sort of dosing -- there's a lot of nausea and vomiting. So we can combine GLP plus PCSK9, but so far, we have not announced that, that's a combination that we're actively doing in the clinical trials website at this point.

And this question comes from Jason Gerberry, Bank of America.

Just another lavender question. How do you guys think about the opportunity for injectable PCSK9 switch versus is the bulk of the opportunity more in PCSK9 naive patients. And 1 thing that we've noticed with injectable PCSK9 relative to statins is pretty low use in the primary care setting. So how do you see kind of the availability of now an oral when you say democratize access to sort of adoption dynamics in the primary care setting?

Yes. Thanks for the question. As we've said many times, we are not focusing this market on how do we take share from the injectable PCSK9s. If you look today, injectables only reach about 5% or less of the total market. We're sitting today here in the United States with 30 million people receiving lipid-lowering therapies, who are not at their recommended LDL levels and who -- even more who go untreated.

So the potential here is much bigger. What we are about is market expansion and helping people understand that cardiovascular disease continues to be the #1 silent killer in the United States. We now have a drug that reduces LDL, which is 1 of the leading causes of arteriosclerosis, leading to that cardiovascular death, by up to 60% on top of statins and everyone who is at risk should be on 1 of these medications.

So our goal is to expand, build the market, educate the market, and we're doing that with what we're doing with the guidelines. Obviously, this will all take time because there is inertia we're working against. But if we are successful, this frankly, should raise the water for all boats and not be 1 where we're taking share.

Yes. And in relationship with the inertia, I think like, for example, the American Heart Association, the American College of Cardiology and other important associations realize the inertia. So they specifically changed the guidelines. And for right now, for example, for secondary ASCVD, they actually said the vast majority of that secondary ASCVD should be less than 55. There's another patient population in there that could be less than 70.

But the vast majority of people with secondary ASCVD should be less than 55, which is consistent with what Europe and other countries do. And in the prepared remarks, I did say that we are not just advancing this with an approval and a launch in the U.S., but we're under regulatory sort of discussions and review with the European Union as well as China.

And to add to the comments that Rob and Dean have made -- what we've seen thus far is extremely strong feedback from key scientific leaders, understanding the change in the guidelines, understanding what this product can do to help patients.

What we need to do is to translate that to the primary care setting. So that will take some time for us to do so. But our sales teams will be focused on ensuring the right education to the primary care setting as well as to patients on the importance of this medicine.

Your next question comes from Mohit Bansal with Wells Fargo.

I have a question regarding the flue drug program, CD38. Can you talk a little bit about what -- like what were the reasons why you decided to add 1 more seasonal northern hemisphere here. And I think the big question here is that was this decision based on any data you have seen? Or is it was just to satisfy with regulatory components rather than any confidence or lack of confidence in the data so far?

Thank you very much for that question. So just to highlight, this is a first-in-class once-per-season strain agnostic antiviral that we're doing for the prevention of flu, especially for those people who are at high risk. What we have said all along is that we plan to launch in 2029 and that, at the same time, I needed to do CMC work in relationship to getting it from 3 shots to 2 shots.

And so that's the rate-limiting step. I also said that between now and that time, I would do everything to have the most robust label and the robust packages that would allow us to have a broader footprint of sites to support a global registration and allow me to get the right value proposition in ex-U.S. markets, especially something that we have to think in the day and age of MFN.

We've also added key secondary endpoint, which is all caused hospitalization, which I think will be critical in that pursuit. And finally, we're collecting data on subgroups and diverse circulating viral strains throughout the world as we do this. I was also very clear that I did not need and would not take an interim. I did not take or saw an interim. I am going to maximize what this molecule can do in the time frame that I need to such that I do nothing to imperil the launch timing of 2029, but that have the most robust label as well as robust real-world evidence that will be important for health authorities.

Maybe just to summarize all that, there's no change in our confidence nothing we've seen in data. This is all about strength of filing given the fact that we have the time because we do have to do the bridging study that Dean mentioned.

Our next question comes from Evan Seigerman with BMO Capital Markets.

Kind of a key theme from this call talked about the $70 billion a potential opportunity that you talked about over the next wave of products. What's the biggest risk to achieving this number? And conversely, which programs in the past 6 months have increased in your confidence?

Yes. Thanks for the question. I mean, obviously, I would say, if you look at where we have confidence from what we've seen, it's the fact that we're getting readouts faster than expected. When we talked about this back in January, we had highlighted sac-TMT as well as IDXD as not having readouts until we got until 2027. We've now seen positive readouts from both.

The Tuli has read out faster than we expected. -- everything is moving. So as we sit here today, my confidence is higher than it was in January because we are seeing meaningful derisking. As you recall, at that time, we said there were 10 programs that represented 70% of the $70 billion. And the fact that so many of those are already having positive data.

So we are clinically derisking them, and we're seeing good launches of those that are underway including an accelerated launch of LIPENDRA by several months. It's hard to frankly point anything I'm worried about. I'm actually feeling quite bullish across the board. Got to knock on wood because things are going well. But credit to our scientific team and the strength of the clinical studies we put in place. I feel very good about where we are.

thank your next question comes from Asad Haider with Goldman Sachs. .

Maybe for Dean, on the PD-1 VEGF bispecific program, just any updates on how the pace of that development is progressing and how you're thinking about any potential read across from Summit how many data coming up? And any update on where you are with potential combination trials with the PD-1 VEGF and your ADC assets?

And if I can just have a quick follow-up on TL1A, I know it's been discussed a lot already, but I just appreciate any context or color that you have on where you are with evaluating combination approaches, which is whether field and IBD seems to be moving towards, so how are you thinking about TL1A as a single agent in terms of its competitiveness versus these combo trials that J&J and Avia aggressively are pursuing?

Yes. In relationship to the PD-1 VEGF sort of story, the way that I think about it is there's a large body of data in relationship to where PD-1 is active, we ourselves have 44 and other people have others. So there's that. There's also a body of evidence of where VEGF is active as well. So you look at that overlap, and that's the place that you would go first.

The other sort of thing is that in some of those tumors, we have unique assets that can be combined and that we know are active. So we're going to focus our efforts on PD-1 VEGF in those 3 sort of then diagrams where we are uniquely able to move forward. We are very interested in following the Summit Akeso data. We think that that's important data for us to follow. But this is our sort of general strategy of PD-1 VEGF in relationship to PD-1, where VEGF is active and where we have unique assets that we know are active that could be combined.

In relationship to combination, you're exactly right. The whole immunology field is trying to think about how it can go to combinations. There has been lots of combinations in the past. T&F and IL-23, there are some evidence that, that would be important. So when we look at TL1A, we're looking to have 1 of the most effective, if not the most effective anti-cytokine, in whatever the indication we have -- but we think it's also very important to know that the safety profile is extremely clean, which then makes it possible to do combinations.

The combinations that you would do, for example, in IBD would be different than that of HS, which would be different than what you might do for rheumatoid arthritis. So for each 1 of those indications, we are looking at the profile of our TL1A and also asking what is the ideal combination for that indication.

Your next question comes from Luisa Hector with Berenberg.

It's another 1 on LIPFENDRA, please. Just the specific wording on the label, which talks about production, but then the cardiovascular outcomes trials have shown to be have shown that you get a reduction in LDL also leads to the reduction in events, specifically for monoclonal antibody PCSK9 inhibitors.

So just wanted to check whether that wording is a help or a hindrance as you speak to payers and as you go about your promotion? And then still on this CVOT topic. What is the timing of your LIPFENDRA CVOT? And can you comment on how you can ensure that drop in use of increasing for weight loss won't impact the result. Would you expect that to be balanced across arms if it does happen?

Yes. So let me answer that question. I need to be a little bit careful to talk about what the intention of the FDA of putting note that they put in the label. I think it's going to be extremely helpful. We believe that LIPFENDRA should be added on top of statins. So I think that's really important. We also know that the design principle, the design principles of LIPFENDRA, the agency understood was informed by the 2 antibodies out there.

So I think that it could be helpful from a commercial standpoint, but I think that was the way that we -- that the FDA and ours, the discussion was. I should emphasize that we do not have CLT right now, and we have an ongoing trial that will read out in 2029.

Great. Thank you, Louisa. We're going to end the call there. I know there's a pure call about to start. So thank you all for your time and attention this morning. We appreciate it. We look forward to catching up at your convenience.

Thank you. This does conclude today's conference. We thank you for your participation. At this time, you may disconnect your lines.

Welcome to the Merck & Company Inc. Rahway New Jersey USA. Investor Event following the 2026 International AIDS Conference. [Operator Instructions].

I would now like to turn the call over to Mr. Peter Dannenbaum, Senior Vice President, Investor Relations. Sir, you may begin.

Thank you, Amanda. Good morning, everyone, and thank you for joining us for Merck's HIV Investor Event following the 26th International AIDS Conference that took place in Rio de Janeiro, Brazil last week. Before we get started, I'd like to remind you that some of the statements that we make today may be considered forward-looking statements within the meaning of the safe harbor provision of the U.S. Private Securities Litigation Reform Act of 1995. Such statements are made based on the current beliefs of our company's management and are subject to significant risks and uncertainties.

If for our underlying assumptions prove inaccurate or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements. Our SEC filings, including Item 1A in the 2025 10-K, identify certain risk factors and cautionary statements that could cause the company's actual results to differ materially from those projected in any of our forward-looking statements made this morning. Merck & Company Incorporated Rahway, New Jersey USA undertakes no obligation to publicly update any forward-looking statements.

During today's call, a slide presentation will accompany our speakers' prepared remarks. These slides and our SEC filings are posted to the Investor Relations section of our company's website.

Joining me today are Dr. Eliav Barr, Senior Vice President and Chief Medical Officer; Dr. Liz Rhee, Vice President of Clinical Research for Infectious Diseases, and Brian Foard, Executive Vice President and President, Specialty Pharma and Infectious Diseases business unit.

Now moving to the agenda. Eliav will begin with an overview of the HIV landscape and our strategy. Liz will then discuss the data that was presented at AIDS2026 and Brian will finish by discussing the commercial opportunity associated with our portfolio before we then move to Q&A. During Q&A, we will be joined by Gregg Szabo, Head of our global HIV franchise.

With that, let me turn it over to Eliav.

Thank you, Peter. Good morning, everyone, and thank you for joining us today. We are meeting at an exciting time for our HIV development program. At AIDS 2026 we presented important updates across several programs that have a potential to improve outcomes for individuals living with or at risk of HIV infection. Most notably, we shared positive Phase III results from the ISLEND-1 and ISLEND-2 studies, evaluating once-weekly ISLatravir plus LENacapavir while continuing to advance our broader efforts in both treatment and prevention.

Now before discussing our strategy and the data presented at the AES conference, I wanted to step back and frame how we think about HIV today. For more than 4 decades, Merck has remained committed to HIV research innovation. Over that period, the HIV epidemic has transformed from a uniformly fatal disease into a chronic, manageable condition for many people around the world.

At the same time, we are far from ending the damage caused by this epidemic. Despite the availability of active anti-retroviral regimens and prophylaxis options, we are far from meeting the 2030 goals. Public health authorities have set some years ago.

Progress has slowed for many reasons. The most important of which are the known limitations of current HIV treatment and prevention regimens and the evolving nature of the epidemic. Now putting a real dent into the HIV epidemic will require a diverse set of highly efficacious treatment and prevention strategies that reduce the burden on people and practitioners and fit seamlessly into the fabric of the communities impacted by HIV.

Now many of the medical tools needed to further reduce the impact of the HIV epidemic are already within reach in our pipeline. We are focused on developing simple, easy-to-use pills that can be highly effective oral treatment and prevention regimens. Now we've made tremendous progress over the past year in our clinical development program. We now have a new approved daily treatment option, positive Phase III data supporting a potentially first once-weekly oral treatment regimen, continued advancement of another weekly oral program to provide more choice and ongoing Phase III development of a monthly oral PrEP pill. Today, we're excited to share with you our innovative weekly oral approach to treatment and monthly approach to prevention. With that, let me turn it over to Liz.

Thank you, Eliav. Good morning, everyone. I'm so pleased to be here this morning to share with you the data we presented at AIS 2026 across both of our weekly oral treatment programs. I'll begin with the Phase III results for islatravir lenacapavir and then discuss the Phase II data for islatravir ulonivirine and the path forward into Phase III. This slide highlights how dramatically HIV treatment has evolved over the past decade. It has progressed from the early days when complex regimens required as many as 16 pills per day or more than 5,800 pills per year to the modern single-tablet regimens that are taken daily. Today, we are evaluating the potential for once-weekly oral treatment, reducing the floor for pill burden from 365 tablets per year to just 52. The data we presented at ADS on our 2 weekly oral treatment programs that are given weekly support that next step in HIV treatment evolution.

We'll start with ISLEND-1, which is a global Phase III double-blinded study evaluating islatravir lenacapavir, once-weekly 2-drug combination given orally against the daily 3-drug treatment of bictegravir FTC TAF, studied in virologically suppressed adults. In this trial, a total of 607 participants were randomized 1:1 to each treatment group. The primary endpoint was HIV RNA greater than or equal to 50 copies per milliliter at week 48 by the FDA snapshot analysis. Secondary endpoints included rates of viral suppression, CD4 cell count changes and treatment discontinuations. Results for -- in ISLEND-1 for islatravir lenacapavir show that noninferior efficacy was achieved against the comparator bictegravir FTC TAF. The regimen demonstrated efficacy as well in terms of rates of viral suppression, which were above 90% through week 48. And importantly, there was no treatment-emergent resistance to either islatravir or lenacapavir in this trial.

These strong efficacy results support the potential for islatravir lenacapavir as the first complete once-weekly oral treatment regimen for HIV. In ISLEND-2, the second Phase III trial, we also evaluated islatravir and lenacapavir. But in this study, the design was open label and the comparator was a variety of daily oral treatment regimens. In this study, we enrolled 626 participants who are randomized to these 2 regimens. And similar to ISLEND-2, islatravir lenacapavir also demonstrated non-inferior efficacy. Rates of viral suppression as well in this study remained high at approximately 95%. Importantly, in ISLEND-2, because of the open-label study design, we had the opportunity to examine participant satisfaction with weekly oral treatment. Participants reported being more satisfied with islatravir and lenacapavir than with their standard of care therapies that they had come in on and as well found islatravir and lenacapavir to be less of a burden compared with daily orals.

We were very satisfied, and we are very pleased to see the satisfaction rates. In addition, safety across ISLEND-1 and ILand2 were consistent. islatravir lenacapavir was well tolerated with a safety profile comparable to bictegravir FTC TAF and standard of care regimens. There were no clinically meaningful changes in lymphocytes, CD4 counts or body weight that were observed, and there were no participants discontinued due to declines in CD4 or absolute lymphocyte counts. Taken together, these data support the potential for islatravir lenacapavir to become the first oral once-weekly oral single tablet regimen for the treatment of HIV. Across both Phase III studies, we observed high rates of viral suppression, no resistance signals and safety and tolerability comparable with the control arms. We look forward to submitting islatravir lenacapavir to global regulatory authorities and working to bring this innovative weekly option to appropriate people living with HIV as quickly as possible.

I'll now turn to our wholly owned investigational once-weekly oral treatment regimen containing islatravir and ulonivirine. As we've discussed in the past, the once-weekly 2-drug combination of islatravir and ulonivirine has the potential to be the smallest weekly pill approved with no loading dose and a favorable DDI profile. In addition, this is being evaluated not just in virologically suppressed but also in treatment-naive participants. At AIDS 2026, we presented data from the Phase IIb trial of islatravir and ulonivirine with week 24 results demonstrating that the combination maintained viral suppression and demonstrated efficacy comparable to continuing daily bictegravir FTC TAF. There were no participants on the islatravir ulonivirine group with an HIV RNA greater than or equal to 50 copies per ml and viral suppression rates were high at over 94% of participants remaining suppressed. Importantly, there were no treatment-emergent resistance cases detected. In the trial, islatravir ulonivirine was generally well tolerated. There were no new safety concerns identified. In addition, the adverse event profile was comparable to bictegravir FTC TAF, and we observed no meaningful effect on lymphocyte counts or CD4 counts. Based on these results, we plan to advance islatravir line into a comprehensive Phase III program. The SYMPHORIA studies will evaluate this combination in both virologically suppressed adults switching from daily therapy and in adults with HIV without prior treatment experience. The Phase III trials in virologically suppressed adults SYMPHORIA #1 and #2 are anticipated to open in the first half of 2027. SYMPHORIA #3, the study in treatment-naive participants is a Phase II/III trial. The Phase II component has been completely enrolled, and we anticipate results in the first half of 2027. With that, I'll turn it over to Brian.

Thank you so much, Liz. And good morning to everyone. I'd like to first start off by saying that it is particularly exciting to join a company with such a rich history over 4 decades and enduring commitment to HIV. I'm energized by the science, the innovation and the possibility of helping provide new options for HIV prevention and treatment. Now as you heard from Eliav's, continued progress against the HIV epidemic will require a diverse set of prevention and treatment strategies. The HIV landscape is also continuing to evolve. People with HIV are aging. Roughly 1/3 of people living with HIV have comorbidities today and the need to manage multiple different therapies for comorbidities is likely to increase. While the existing antiretroviral medicines are generally safe and effective, certain classes also can impact renal, bone and other areas of health differently, further highlighting the need for multiple treatment options with different mechanisms.

And for the majority of people living with HIV who choose daily oral treatment options, despite the important progress that has been made, the daily pill burden remains. Daily dosing can contribute to treatment fatigue and stress as well as concerns about inherent HIV status disclosure. In prevention, opportunity remains to reach more people who could benefit from HIV PrEP. Starting and remaining on PrEP can be complex and many people who could benefit from prevention remain unreached. We are advancing a series of potential options designed to address these evolving needs. Idvynso, our newly approved once-daily oral treatment, marks the beginning of a broader portfolio strategy. Idvynso is the first and only non-INSTI, tenofovir-free once-daily complete 2-drug regimen to demonstrate non-inferior efficacy in a head-to-head Phase III trial versus 3-drug regimen, BF/TAF. Idvynso provides people living with HIV an important new option when looking for switch therapy.

The key drivers of switch include tolerability, desire for simplification from multiple tablet regimens to 2-drug single-tablet regimens, comorbidities and drug-drug interaction considerations. We're pleased with the launch progress so far, including the early access announcements and look forward to access ramping up over time. Beyond Idvynso, we are preparing to bring forward weekly oral treatment options and looking ahead to our entry into PrEP, where we are aiming to launch the first monthly tablets. I will address each of these opportunities in turn. We are particularly excited about the potential for ISL/LEN to be the first once-weekly oral treatment option. The need for additional treatment options remains clear as many people living with HIV continue to experience challenges related to daily dosing fatigue, stigma and the practical constraints of injectable therapies. Weekly oral therapy offers a less frequent dosing approach that aligns with preferences frequently expressed by people living with HIV.

In collaboration with Gilead, we look forward to sharing the positive results from ISLEND-1 and ISLEND-2 with regulatory authorities with the goal of bringing ISL/LEN to adults living with virologically suppressed HIV as quickly as possible. One of the strengths of this opportunity is that it combines what we believe is a highly differentiated product profile with the capabilities of 2 global organizations with a shared commitment to advancing innovation for people living with HIV. From a launch perspective, planning is already well underway. The collaboration structure allows both organizations to prepare for commercialization while coordinating around a shared global strategy. For the long-acting oral program, Gilead will lead commercialization in the United States and Merck will lead outside of the U.S. Finally, I'd like to briefly touch on Alimatravir, our investigational monthly oral PrEP.

This differentiated approach offers the potential for discrete monthly dosing and a rapid onset of protection predicted within 1 hour. Alimatravir is a molecule developed specifically for prevention. The Expressive 10 and 11 trials are anticipated to read out in 2027. Recently, we announced initial plans intended to support rapid, broad and sustainable access to Alimatravir in low- and middle-income countries should it ultimately be approved. Those plans include voluntary licensing agreements covering more than 129 countries, support for regional manufacturing capabilities and investments intended to facilitate timely access following approval. We believe innovation has the greatest impact when it reaches the people who need it most, and this announcement reflects our long-standing commitment to HIV and global access.

Now stepping back, we believe the combination of Idvynso, ISL/LEN, islatravir/ulonivirine and alimatravir creates a meaningful long-term opportunity. We see an opportunity of greater than $5 billion on a non-risk-adjusted basis by the mid-2030s. These programs reflect a long-term commitment to advancing HIV science and a vision for a future in which prevention and treatment are increasingly simple, accessible and fit seamlessly into the fabric of the communities impacted by HIV. And with that, I'll hand the call back over to Peter.

Thank you, Brian. Amanda. We're now ready to begin the question-and-answer portion of the call. Before we get started, I'd like to request that today's questions remain focused on our HIV treatment and prevention programs.

[Operator Instructions]. Our first question comes from Trung Huynh with RBC.

So just 2 questions from outside. The ISLEND-2 CD4 data that showed continuing -- continually gradual decline of the ISL/LEN arm versus Biktarvy over 48 weeks, even though both arms ended at equivalent levels. ISLEND-1 and the ISO Ulu Phase IIb, they were both modestly better than Biktarvy on this metric, which helps contextualize. But how are you interpreting the ISLEND-2 curve divergence? Is that a baseline imbalance artifact? the class signal you're monitoring or something that you believe will fully resolve at 96 weeks? And how does FDA engage with this in the context of labeling discussions?

And then second question, just can you walk us through the ISO/ULO SYMPHORIA Phase III program in the treatment experience patients specifically design experience patients specifically design, enrollment time line, any expected readout -- and relatedly, what does the 48-week secondary endpoints and treatment-naive Phase II/III data need to show for you to be confident in an NDA path towards that 2030 approval target?

Thanks for the questions. This is Eliav Barr and I'll moderate, but I'll take the first one and then Liz can take the second one. With respect to the CD4 counts in ISLEND-2, there was a small statistical difference in change in baseline CD4 T cell can at the week 48 time point. But we didn't consider it to be clinically meaningful for a variety of reasons. First, as you noted, none of this was seen in ISLEND-1 nor in the Phase II ULO studies.

There was a baseline imbalance as you also noted, the CD4 T cell comp was higher in the ISLEND group compared to standard of care at baseline and the changes were greater in those -- the changes that we observed in terms of CD4 cons were greater in those with the highest baseline counts. So we think that it's probably a regression to the mean. And we looked at a variety of different other factors in the studies, including the percent changes in baseline CD4 T cell counts and discontinuations and other metrics that both Gilead and Merck together assessed from the perspective of changes in CD4 counts. None of these were any -- were statistically significant.

And so bottom line is that we don't see this as being at all clinically meaningful. We don't anticipate this to be a problem with this drug or any islatravir containing regimen going forward.

And in terms of the SYMPHORIA trials, let me turn it over to Liz.

Sure. Thanks, Eliav. So for the Velogica suppressed indicationlogical, we are planning 2 studies, as I've indicated earlier, SYMPHORIA-1 and SYMPHORIA-2. Both of these studies in terms of primary endpoints will follow FDA guidance. with the primary endpoint being those with viral load greater than or equal to 50 analyzed by the FDA snapshot. We would also be looking carefully at safety, of course, in these studies. And I think with SYMPHORIA #1, which is an open-label study, we would have opportunity as well here to collect PRO or patient-reported outcomes such as satisfaction as we had done in other weekly trials. At this point, we are anticipating starting studies in the first half of next year. The details of the secondary endpoints and time lines of the trials, we don't really have ready to share at this point in time, but we will share them in the future when they are ready.

We are in the process of sharing our plans and discussing with the FDA.

Just to be clear, I think the SYMPHORIA studies are going to be a very important addition of the Q week regimen. Just to remind everyone, we'll have both treatment experienced and treatment-naive patients. This is something we heard loud and clear at the HIV meetings, a lot of interest in starting people right on QWek to really help them in that period of time when they're still grappling with the fact that they're HIV positive. So we're really looking forward to starting those studies, and we'll let you know about the time lines when we're more set with them.

And one type of regimen is not going to fit all, so one size does not fit all. In addition, as people living with HIV age and deal with comorbidities, there is particular concern on effects, for example, on cardiometabolic factors, on weight that can lead to people needing to switch due to tolerability issues as well as drug-drug interactions as people are taking more medicines for their comorbidities. So Elliot, to your point, we hear loud and clear from providers and also patients themselves, people living with HIV that they want more options and that integrase is not going to solve every problem for them.

Our next question comes from Evan Seigerman with BMO Capital Markets.

Malcolm on for Evan. So you framed a $5 billion non-risk-adjusted opportunity in the mid-2030s from new and potential HIV launches. I know that this reflects Merck's share of collaboration revenues. Can help us think about the relative contribution of treatment versus PrEP within that $5 billion target?

Thanks for the question. I'll ask Brian and Gregg to address.

Yes. Thank you so much, Eliav. And I think it's a really great question. And just as we're talking about today, think about it overall, first and foremost. We're talking about four potential therapies, one is approved in the marketplace today with IDVYNSO and then three additional potential options for those living with HIV or looking for PrEP. And so we framed it first and foremost in the treatment category. The treatment category today in 2025 is about $26 billion. We're expecting that to continue to grow to more like $32 billion by the mid-2030s.

We're also expecting the PrEP market space today, which is a much smaller market space. It's about $4 billion today. We expect that to more than double over time, and we see this as a significant and meaningful reason for us to be in this space with these potential therapies. So maybe, Gregg, if you want to give a little bit more detail to it.

Thank you, Brian. I would really start by mentioning the very positive reception that we had at the Congress last week for our data and for our portfolio. We had a strong positive reaction across scientific leaders, prescribers and advocates, and it really gives us growing confidence in our potential to achieve that greater than $5 billion revenue by the mid-2030s. I think that as Brian laid out, we've got several options, and each of these programs is well differentiated and I think brings significant value to the space.

In talking about the treatment market, which is the larger market, we do see evolution today, and we expect it to continue into the future towards two-drug regimens and also towards long-acting regimens. Ultimately, we expect long-acting regimens to represent a solid majority of patients by the mid-2030s, and we feel the two weekly orals will have a strong place within that segment. Each of these assets, including alimatravir in the PrEP space, will be contributors to that overall $5 billion number. And I think alimatravir just has such an exciting profile with rapid onset once monthly discrete oral dosing, and we believe that also will be an important option within the PrEP space.

Our next question comes from Alex Hammond with Wolfe Research.

Can you kind of walk us through how we think about alimatravir in the context of the PrEP market that's actively organizing around injectables? Who the target patient population is, how you're thinking about that window before you as an amplitude establish those deep prescriber and infrastructure relationships? What the access and pricing strategy might also look like in both the high-income and high burden markets?

Thanks for that question. Let me start by saying that for the PrEP market, what we've heard very loud and clear is the need to have regimens that are seamlessly integrated into communities that require minimal medical intervention, that enable patients to have access in various locations, that don't require the need for advanced care. And with all of that in mind, we think that an oral monthly would be very, very useful indeed. In fact, if I have to say what was just a wow moment for everyone at the AIDS meeting was alimatravir. We could not get away from anyone who wanted to say something about alimatravir, to think about alimatravir as part of their treatment regimens and so on. Maybe I'll turn it over to Gregg to talk a little bit about his impressions.

Thanks, Eliav. I would start by saying that despite the availability of a number of highly effective PrEP alternatives today, either daily orals or injectables, we still see many new infections, and we still see that a relatively small percentage of people who can benefit from PrEP are actually taking it regularly, certainly less than half the people in the United States and less than one in five globally. And there could be a number of reasons for this. Some of them are just low perception of risk on the part of the patient or low awareness of PrEP, but there's also a number that are potentially mediated by the drug profile itself, and these include things like concerns about side effects or tolerability, the stigma that's associated with using PrEP and also suboptimal ease of implementation and accessibility within the health care system.

So we feel very confident in an oral once-monthly pill. We believe this is something that's easy to access and that it doesn't require HCP administration. The fast onset of action, that was something that got a lot of favorable feedback at the conference last week. Current options often take days to be effective. We believe that alimatravir can be effective within an hour. It also has a favorable DDI profile, which can be really important within this population. And with regards to stigma, this is something that can be very discretely taken or stored to really protect the user's privacy and avoid stigma. So ultimately, we feel like this opens up new models of implementation to increase the number of people using PrEP, and we also feel it has a very strong value proposition relative to all the other options that will be available.

Maybe just a couple of extra points here. While it's too early to really specifically speak about the access strategy as it relates to that, we do think that it does have a compelling value proposition and key differentiation, which should assist in gaining access.

We're also, too, and I want to make this point because I think it's an important one. We're encouraged by the SCOTUS ruling for the USPSTF that was important for individuals to access PrEP with no out-of-pocket cost and has implications for all preventative and services and medicines. And so the environment is set up for innovation, and so we're excited about potentially bringing that innovation.

Our next question comes from Geoff Meacham with Citibank.

Another one on the weekly oral. I just want to get some perspective on the PK/PD. Do you have residual drug extending beyond a week? I'm just thinking about real-world compliance and the risk of resistance. And then commercially, would you view this as a switch opportunity at the onset? Or is it more upstream to perhaps newly diagnosed patients?

So let me ask Liz to talk a little bit about PK/PD and the forgiveness that's already in the -- in our 2-week regimen. And then I'll ask Brian and Gregg to talk about the commercial potential. Liz?

Right. So for both of the oral weekly regimens, islatravir, lenacapavir as well as islatravir, ulonivirine, the doses were selected to enable a window for forgiveness of about 7 days. And this is to take into account the fact that people may forget to take their dose on a certain day, they need a window to catch up essentially. So that week of forgiveness means that if you forget your dose on a Monday, you have a week to get back on, and then if there -- if that window is exceeded for each of these programs, we have thought really carefully about how people would need to then restart the regimen. So this has been factored into the development program in the Phase III studies. So from that perspective, we feel that there will be very clear instructions for participants on what to do if they do miss a dose and outside of that forgiveness window.

And indeed, in the Phase III trials, compliance was extraordinarily high and a lot of satisfaction around the use of q-week and subcu. But maybe I'll ask Brian and Gregg to talk about the other piece.

Maybe just at a really high level, and then I'll pass it over to Gregg for a bit more details. We know, again, in the treatment space, as I mentioned before, this is one of the biggest areas today, and we anticipate it will continue to grow. And just as Liz nicely said, we believe it's because individuals like options, and this is really important to continue to bring options. I know you didn't necessarily specify which weekly option, but it's exciting to be bringing two, to be quite frank. And so maybe Gregg can give a bit more details about the two opportunities as we see it.

Yes. Thanks, Brian. And I think you're right. I mean options are important. Obviously, if you look at the daily market, there's been continued innovation there that ultimately has led to more and more satisfaction for patients as time has developed, and we think the same thing can happen with long-acting therapies as well. If I start with isl-len, again, I think there was a great reaction at the Congress last week. This has the potential to be the first weekly oral regimen to market. There's really strong patient interest and it's highly differentiated. And I want to double down a bit on the patient interest because I think this is something that is really important from the perspective of the long-acting oral regimen. It has the potential to address pill fatigue. This is an important issue for people living with HIV. And also the potential to address what can be injection fatigue. I mean any -- this is designed ultimately for people who want more freedom that they can get with less frequent dosing, but not be tied to a physician visit for administration.

So obviously, we're excited about isl-len because it brings together two highly potent agents that have the potential to maintain the viral suppression and do it with reduced dosing frequency. But then if we move to isl-ulo this is also a highly effective program based on our Phase II data so far, effective with a small two-drug tablet. This has the potential to be the first weekly regimen that will address treatment-naive patients. As Eliav mentioned earlier, this could be an important opportunity to really start people, especially when they're undergoing reaction to being diagnosed with HIV.

Also importantly, there's no loading dose associated with isl-ulo. As I mentioned, the small pill and it has a favorable DDI profile, so we believe that the unmet needs and the desire to switch to easy oral dosing for once weekly will persist beyond the launch of islatravir and lenacapavir, and we see isl-ulo continuing to expand that market category. And over time, we feel the biggest opportunity is really moving people from daily to weekly, supported by a portfolio of differentiated options.

Our next question comes from Vamil Divan with Guggenheim Securities.

So maybe two follow-ups on one, just on the comments you were just making around isl-len versus ulo, so I appreciate some what you said there on the benefits of ulo, may provide in terms of no loading dose molecule paired with DDIs. How about the other way around, if both of them are available, what would be the benefits of isl-len other than maybe getting to the market first? And then the second, you spoke previously around the $5 billion commercial opportunity and the sort of breakdown between PrEP versus treatment, I'm curious if you can give any sort of similar breakdown on how you see the U.S. versus the ex U.S. contribution to that greater than $5 billion number.

Thanks so much, Valim. Let me take the first, and then we can talk about the commercial elements. So it's exciting to have islatravir, lenacapavir as the first drug because lenacapavir's safety profile and efficacy profile are well known and understood. They're part of a lot of -- lenacapavir is part of a lot of regimens, and so we have here a new class of drug that has a strong and well-defined efficacy safety profile. And people are aware of the drug-drug interactions that one needs to keep in mind.

So islatravir and lenacapavir, I think, will be an excellent first option and a continued option over the course of the years along with islatravir and ulonivirine. So if I could switch to Gregg.

Thanks, Eliav. I would just say that this product, these products are highly differentiated, and I think they're going to have a big impact in that regard outside the U.S. as well as in the U.S. We're not specifically breaking down the opportunity across geographies at this point in time. But I would say one could imagine something similar to the breakdown in the current market for HIV.

One last point that I'd make about that, too, is we get this question commonly about these two assets. I think one is important. The first asset actually comes with the power of two organizations that have been in this space for a long time. But we think about that space, the long-acting is really where the growth is going to be in the future. And so we believe that marketplace is going to be largely dominated by the long-acting therapies, and so while we don't -- we're excited about bringing two therapies, we're not necessarily thinking about one versus the other. We think the space is going to have options, and we think a lot of the growth is going to be there for the longer-acting treatment versus PrEP.

Our next question comes from Chris Schott with JPMorgan.

Just coming back to the role of your initial weekly islatravir-len. Can you just elaborate a little bit more in terms of the role that can play in the treatment experience market? I guess specifically, what percent of the market do you think this can address? And when you think about switches, how quickly can ramp as we think about that commercial opportunity?

And then my second question is just given some of your peers are pursuing injectables in both PrEP and treatment. Is this an area Merck is looking to explore as you just mentioned the market is bifurcating less options, like is there an opportunity to take these assets into longer treatment regimens?

So let me take the second one first, and then I'll turn it over to Brian and Gregg. Of course, we're looking at all different options, and we have a robust discovery pipeline. The past few years at Merck, we really focused on simplification. And if you think about LIPFENDRA for example, as a simplification option compared with injectables and then you apply that to the HIV space, it's the reason why we spent a lot of time thinking about easy to administer long-acting orals that will ultimately make it just much less complicated to get patients their medicines with reasonable access. So that's where we are right now. But of course, we're looking at all manner of opportunities to provide both treatment and prevention. We'll look at that in our discovery pipeline, and we'll be able to share some of that as the drugs progress into later development. So Brian, Gregg?

1

Maybe I'll start and then, Gregg, if you want to add anything additional to it. I think first and foremost, the market today, the treatment market today is largely daily therapies. I mean, so we believe the longer-acting therapies are going to play an important part, as I just mentioned a moment ago. And number two, as you look at today from a switch standpoint, about one in five people living with HIV switch annually for a variety of reasons, tolerability, long-term toxicities concerns, comorbidities, as we've mentioned before, and desires for simpler regimens. And so we believe, again, for a variety of reasons, it will create a significant opportunity there. But I don't know, Gregg, if there's any additional points you want to make?

Yes. I would just reinforce again that we do see current evolution in the market, both within and away from, I guess, the daily class. So within the daily class towards two-drug regimens and then towards two-drug long-acting regimens. We do expect that to continue. And as mentioned earlier, we really expect the long-acting regimen to ultimately represent the solid majority of people within the market. Within that, we could -- we see a solid place for the q-weeklies. We could see that ultimately getting to about -- overall, about 1/3 of the overall treatment market. And I would just reiterate the strong patient preference. And I think that will also help with the initial ramp is there is a strong patient-driven aspect to these long-acting oral therapies. There are people that want to get away from that daily pill and want to also may not be right for injectable treatment. So we do feel that progress will be substantial in this space.

Our next question comes from Daina Graybosch with Leerink Partners.

Two on alimatravir, I hope I said that correctly, wonder if you could talk about a weekly monthly prep versus a weekly oral prep, why monthly might be better or differentiated from weekly? And then a second question, you talked about the hours onset. Is that something you can measure as an outcome? And will you measure it in many of your registration trials so that gets on label? And does that matter for that differentiation to really get out there and be used by clinicians in the community?

Thanks. I'll ask Liz to comment on the clinical trials program. In terms of weekly prep versus monthly, the ideal for people who are in a prevention mode, right, this is not infected individuals, is to have as little as possible need to do anything really to get protected. So just as much as -- as little as you go and go somewhere to get an injection, you want to just get it and be done with it. So I think that the longer the interval on the oral, the better in that circumstance. The other piece of that is with regard to the second question that I'll turn it over to Liz to talk about is I don't want to think about it and plan ahead because it's Saturday night, et cetera, et cetera. So being able to have your PrEP available and effective within an hour is consistent with what life is really like. And Liz, do you want to talk a little bit about the PK.

Right. So actually, at CROI earlier this year, we presented PK data for alimatravir and justification for the 11-milligram monthly dose that was selected. And as part of the dose selection process, we looked carefully at the PK and at the onset when we expect drug levels to be at above the threshold that we expect to be efficacious. So the 11-milligram dose has this baked in where you'd expect levels to be protective within 1 hour. There's no need for a loading dose. There's no need for a higher dose to start with. I think the dosing regimen itself is quite simple because of these PK attributes. In terms of the label, I mean, the PK section of the label will include all of this data. We are collecting PK data in the Phase III program, and we'll be able to report that out.

And I would add that there's been a lot of interest in this PEP study, post-exposure prophylaxis program, and we are taking that under advisement. Maybe I'll turn it over to Gregg for the commercial side.

Yes. And maybe just one last comment that I would make that one of the key things for PrEP is avoiding the stigma associated with taking PrEP and having a longer option such as a monthly and an oral option where you're not having to have frequent trips to the physician to have that administered, this can be very helpful. So a monthly versus a weekly, for example, just gives you less opportunities from being observed, taking the product. It gives less opportunities for somebody finding stored products. So it allows for a lot more discretion that can really help to protect the users' privacy. And we think this will ultimately be something that's very important within the community.

Our next question comes from Carter Gould with Cantor Fitzgerald.

I want to come back to alimatravir. As you think about the bar for efficacy here, I recognize the studies are against DF/TAF, but the cross-trial comparisons are pretty straightforward and PURPOSE 1 and 2 set a pretty high numerical bar there. In light of all your commentary around the differentiating features, does Merck sort of address this with potentially some more leniency on efficacy in terms of the bar they might be held to? Or from a clinical and regulatory perspective, is it going to be critical they match that sort of very high 90s sort of bar we saw in PURPOSE 1 and 2?

Yes. The standard that is applied for all of the prep drugs are the same with -- in terms of regulatory agencies, and so our expectation is that this will need to have the same kind of efficacy that would meet those statistical criteria.

Our next question comes from Jason Gerberry with Bank of America.

Just two follow-ups. You mentioned potentially the ability to get 1/3 share in the treatment market with islatravir-len. What is your assumption regarding ability to take share from injectables? Do you view the injectable space as sort of a separate segment that's harder to claw away share? And is the assumption mainly that it's an oral switch? And then just as a follow-up, any updates? I mean last time you did this call about a year ago, you talked about your injectable options being early stage, but when do you think we could be in a position to potentially get an update on the efforts Merck has with its injectable offerings?

I'll take the second one first. We're still looking on a variety of injectable options. You see that there's a lot out there, so we don't want to have just something that would be "me too." It would have to be differentiating, and we're working on that. In terms of the commercial elements, Brian, Gregg?

Yes. I'll first start off by saying one of the things that we reiterated a bit earlier is that we feel like in the treatment marketplace, you're going to see the marketplace continue to move to the longer-acting therapies, the weekly therapies. And we're really excited about that today. It's largely daily therapies if you think about where the market is today. So we see the marketplace going to continue to grow, and we think it's going to be growing primarily because of these longer-acting therapies. But Gregg, maybe a bit more specifics.

Yes. I just want to address. I think what we had mentioned earlier around 1/3 was for weekly options, not specifically for isl-len, so I do just want to correct that comment that was made. And I think your other question was, do we see it as primarily coming from dailies versus injectables. I think the value proposition is there for either. But as Brian has mentioned, the market is still today and expected to be next year is still dominated by daily, so I think the pool in which we're operating is likely to be much higher on the dailies side.

Our next question comes from Michael Yee with UBS.

Maybe two questions here. On the weekly treatment option with Gilead, can you just talk a little bit about the economics there and how you think about a profit share there given that the partner already has wholly owned rights on the standard of care and complications of a partnership there in that context and how that works? And then a second question on the monthly prep, which sounds very exciting. Can you talk about the window and margin there for retreatment and compliance there? I know you said fast onset of action, so perhaps there's definitely room just because of the fast onset, but how that works there with the monthly pill on the PK if you miss a dose.

Thanks so much. Liz, could you comment on the forgiveness of the q-monthly? And then I'll ask Brian and Gregg to talk about the economics.

Yes. Thanks, Eliav. And actually, this was also addressed in the data we presented at CROI earlier this year that I've mentioned before about alimatravir. So the 11-milligram dose allows for approximately a week of forgiveness in case the dose is missed.

Thanks. And Brian, Gregg?

Yes. So across the programs that we have with Gilead, Gilead and Merck will share global development and commercialization costs, 60-40, respectively. And then for the long-acting orals, as we said, Gilead will lead commercialization in the U.S., Merck will lead commercialization ex U.S. and Merck and Gilead will share global product revenues 50-50 up to around $2 billion, or up to $2 billion and then 65% Gilead, 35% Merck thereafter.

Perhaps I can just add to that we've had a very productive partnership with Gilead. And I would start with what is the most important point, which is that working together, Merck and Gilead is allowing us to provide a new and important option for people living with HIV. In fact, this is the only way or the way that we could get to the market the fastest with something that will be highly desired by the community. And so ultimately, we've worked well so far, certainly in developing the launch strategy. We're beginning to move into execution. We've established appropriate governance for all the key decisions. We believe it's working well, and I think both companies are firmly committed to establishing the oral weekly category. And isl-len, as we've noted, has the strong potential to be the first option.

Great. Amanda, I know it's a busy morning for most. So we'll take time one more question please.

Our last question comes from Louise Chen with Scotiabank.

I wanted to ask you if you think you have what you need for a full product offering to HIV patients in both your commercial and pipeline products? Or are there other areas that you think will be important for you to be involved in?

So maybe I'll start with the future. Look, I think everyone is looking for new therapeutic classes. This is a disease that people have to grapple with today for 50 -- up to 50 years, and so there are always going to be important enhancements that will need to be made. There's a lot of desire for functional cure. We're working on a lot of those elements, and I think we've got a very unique set of discovery assets and also capabilities given our interest in immuno-oncology and immunology in general to think about how we might address that. But these are our long-term plans. I'll turn it over to the -- to Brian and to Gregg to talk about the commercial element.

I think it's a fantastic question. I think, and I'll pass it to Gregg here in just a minute, I think the key thing for us is to do as we've continued to do for many, many years now is to continue to collaborate with the community and make sure that we understand exactly what it is that they need. And so I think from that, we'll continue to work tirelessly, I think, to develop innovation -- innovative options for the community. Gregg, anything else?

I would maybe just say that we already have, I think, a very clearly defined and well-sequenced portfolio strategy. Each of these assets is really designed to address distinct unmet needs. Each of these assets has meaningful scientific differentiation, and we're putting around that. We've undertaken extensive internal and external benchmarking to make sure that we have the resources, the capabilities, the investment levels that are aligned with the competitive dynamics of the field to make sure that we can be confident in our ability to allow us to compete, and we're confident that we can invest at that level. So I think this begins with IDVYNSO. We're already out there in the marketplace across medical affairs, market access, commercial function, actively engaging with stakeholders, leveraging our long-standing relationships. And so far, the progress has been good, and the reception has been very positive.

Excellent. Well, thank you, Louise, and thank you all for your interest and time this morning. Please reach out to the IR team for any immediate follow-ups, and we look forward to speaking with you tomorrow. Thank you.

Thank you. That concludes today's conference. Thank you for participating. You may disconnect at this time.

All right. We're just about at time. So let's keep moving with our next session with Merck. I'm very excited to have Rob Davis, CEO; and Dean Li, EVP Research Labs. Thank you both for being with us today.

Rob, maybe before we begin, I want to just give you the opportunity to level set us, big picture, on how things are going, sort of, midpoint of the year, how are things tracking towards the derisking of the commercial targets that you said that you'd achieve at least half of by the end of this year. So high-level comments on...

Yes. No, happy to do it. Well, one, thank you for having us. Good afternoon, everyone. If you look at where we're at, it's already been a very eventful year for us so far. And I would say our transformation is well underway.

If you look at the readouts we've had, it's pretty much hitting every area of our portfolio, whether it's Oncology, some important readouts coming from ASCO. HIV, news came out yesterday of our approval of islatravir plus lenacapavir. Ophthalmology, things are moving. Across the board, we feel very good about what's happening in the pipeline. And as I think about proof points, you're starting to see them and they're accelerating, and that's very important.

We're well on track to our goal. You mentioned the 50% of the $70 billion by the end of this year. We're actually ahead of schedule. You saw we had important readouts for sac-TMT, I-DXd, actually about a year ahead of what we thought. So as I sit here today, whether it's that, what we're doing with business development, bringing in Terns, which is another important asset. Our Animal Health business continues to do incredibly well, growing strongly on a new product portfolio strategy, very similar to the Human Health business.

Across all those fronts, what I'm probably most pleased about is it feels like people are starting to dig in and get a real sense and confidence in the breadth and depth of our portfolio and more there, but the fact that you're starting to see investors start to appreciate that, makes me very happy.

And I would just close by saying, as I think about where we sit today, my confidence that we are positioned for good growth coming out of the LOE is as high as it's ever been. It was already high. It just gets better. We're going to keep doing what we're doing. We're never satisfied, but we're operating now from a position of strength, and I think that's probably most important. And credit to Dean, to our MRL colleagues, how they've transformed the pipeline in the last 4 years is frankly quite amazing.

And there's a lot to talk about the pipeline transformation, which we're going to get to. But maybe before we do that, Rob, I just want to stick big picture for a bit. You touched on this briefly, BD, and I apologize in advance for asking you this question again because you've been asked in so many different ways. But I think everyone is always interested in hearing about your latest framing on the M&A lever. Just given the confidence that you're expressing on the pillars that you've already put in place for the transformation of this company that now seem well underway. So what are the gaps that are left to fill? Level set us on size, TAs, et cetera?

Yes. If I was going to summarize it, I would say we are going to continue to execute the exact strategy we've been doing over the last 4.5 or 5 years. And it starts with always asking the question, where is there important science that is happening, addressing an unmet need? Where we see that, we look at the portfolio and we try to think strategically about the portfolio.

And as I think about your question of where we are, I don't know if I see gaps at the moment, I see opportunities. Where I would see further opportunities, oncology. We want and intend to be a leader in broad-based oncology. And I think we now have the portfolio to do that. And we have strength to leverage by adding to it. So we'll continue to focus on oncology. Cardiometabolic is a space we're interested in. Immunology is a place where we're interested in. But we're going to continue to do that. And as you think about it, where we see the science aligned with our portfolio and if we can see value, we will move. We have been operating under a one pipeline strategy since Dean and I really came into our roles. And that means we want to bring in the best, whether it's internal or external.

So this isn't -- we're not doing business development to fill a gap to -- and so there's never a finish. It is just part of an ongoing strategy of how we develop a sustainable growth model that is going to take us not into 2030, not into 2035, but 2040 and beyond. And that's why from a size perspective, that $1 billion to $15 billion, which has been the sweet spot we've been operating in, that continues to be where we operate. We've said consistently that we would go bigger, but it has to be something where we see an important scientific opportunity and we have to see value creation. And obviously, the bar as you go bigger gets harder because it reduces your opportunities to do other things.

So that sweet spot, $1 billion to $15 billion is where we'll continue to focus. You look at what we've done, Verona, Cidara, Terns, those are the type of deals. I think you should continue to expect to see more of that.

Excellent. So before we kind of start drilling into some of the science, with Dean. On one more high-level question, Rob, that we're actually asking all of our management teams is -- and that's on the external environment and the operating external environment for the industry. You've got the midterms coming up. You've got some regulatory uncertainty with FDA leadership vacuum. You've got attempts to codify MFN that's set to expire in about 3 years. So what are you paying the most close attention to? Where are the banana peels that you could run into either on the drug pricing side or on the MFN side or anything else that we should be aware of?

If I look at where the FDA is and what's happening, I would start by saying we need a steady, stable, predictable FDA. That's very important. If you look back over the last couple of years where they've been focused, I do think they were making moves in the right direction, and I hope they continue under whoever comes in now to take over. And that's around how do we move better into the Phase I first-in-human studies. The question always is, why are we looking? Why do so many companies go to China, as an example. Well, it's because you can go faster and cheaper. So why don't we try to make the U.S. [Audio Gap] by addressing and simplifying our Phase I clinical processes that [Audio Gap] we want to see that focus. We want to continue to see a focus on AI. So those are the things we are promoting from an FDA perspective.

From a macro perspective, the push to try to continue to get reforms around PBM insurance, now 340B, I still believe that if you look at total drug spend, it's only 15% of the total on the innovative drugs. 90% of all drugs prescribed are generic. Generic prices in the United States are the lowest in the world. So that is a highly efficient model. So why not focus where the real challenge is, it is the $0.50 that goes into the middle. Why do we lose $0.50 of every dollar when you're not a part of the development, not taking any of the risk, not having to manufacture. We need to address that macro system.

And as an industry, both as Merck and now as Chairman of PhRMA for this year, that's where I'm pushing. How do we continue to work with the administration and with Congress to address those fundamental infrastructure issues but -- that I think are real opportunity. So if we can continue to drive for stability and predictability in the FDA, focus on making our system more efficient and address some of these macro challenges, we're positioned to be the world leader for a long time, but we need to make those moves to do it, and that's where I'm focused.

Okay. So maybe with that, and I have a couple of other big picture questions, we'll come back to those because I want to bring Dean -- I want to bring you into the conversation.

Let's maybe start the discussions coming off of ASCO. But before we get into some of the updates you saw there, I want to just address the EVOKE trial that you and Gilead announced the discontinuation of last night, where the KEYTRUDA plus TRODELVY combination was being tested in first-line metastatic non-small cell lung, PD-L1 high patients. So how should we think about the implications of that for sac-TMT in that indication? What, if anything, should be the read-through there?

Yes. So I [Audio Gap] comparison. And so one has to be a little bit thoughtful on how one does it. But this is in the PD-L1 high. It is looking at the addition of a TROP2 ADC with PD-1. It's very similar to a trial that we discussed at ASCO, where there was impressive data. And in the data that we just had a discussion where we actually put the headline out yesterday with our other partner, Gilead, it didn't meet the bar.

So the way that we look at it is not all TROP2 ADCs might not be the same and that we're very focused on our partnership with Kelun on their unique TROP2 ADC, sac-TMT, which we think is differentiated in the molecular design, and we're very interested in replicating the data that you saw at ASCO in relationship to the China trial and doing it globally. So we think that the opportunity for that potentially is greater, and our job is to bring that through.

So I guess that's a great segue into maybe unpacking that a little bit, arguably, the OptiTROP-Lung05 trial, which I think you were referring to is stronger validating data for sac-TMT than what you saw last night. So really no read-through there despite those both being TROP2 ADCs.

So maybe talk a little bit about the OptiTROP-Lung05 trial. What did you learn and what didn't you fully learn from that program? What are the most important gating points in terms of just trials? And what would you like to see before taking the next steps in the -- for the development of this program in the KEYNOTE-189 population, which has clearly set a very high bar.

Yes. So the first thing is when we brought in sac-TMT, the TROP2 ADC, we were very clear. We thought that this was a differentiated molecule and that there was enormous opportunity outside of lung and breast. So when you see the 17 Phase III trials we have, we've highlighted 13 of them are in tumor types and indications where we're the first movers. What we said in breast and lung is that there will be TROP2 ADCs before us, and we need to highlight the differentiation. And I think we're beginning to do that in lung. And I think there's also data that probably will come out in the next year or so in relationship to breast.

In relationship to lung specifically in KEYNOTE-189, the concept is you have pembro plus chemo in all-comers in non-small cell lung cancer. And the question is, at what point would you take sac-TMT and put pembro in that sort of place. We've decided to do PD-L1 greater than 50%, and that's clearly been a useful strategy.

But the broader thing as to when would you "blow-out" the program within lung. We're already blowing out the program without talking about lung. One of the questions that we always asked ourselves is, will there be innovations on the PD-1 side that we should take into account. And so that's something that we're looking at carefully now with important data coming from Akeso in China. And so we're studying that. deeply. But we've already "blown-out" the sac-TMT program. We're focusing in one component -- part, which is lung.

And I guess the lens for that program on the Kelun side is now starting to shift to the OptiTROP-Lung06 6 trial.

Correct.

So give us some high-level framing on what you would consider to be a successful outcome for that trial? And how does that trial add to your knowledge base around sac-TMT activity across the spectrum of non-small cell lung, including in the less than 1%...

I think that will be an important trial because it will tell you how much weight sac-TMT can hold in the challenging of KEYNOTE-189 and whether or not it would be -- it holds it well enough or would it be better if it held it with another alternative to a PD-1. And I think that's what it will teach us.

And we work very closely with our partners in Kelun. I mean they've just been excellent partners. And so we have -- using their data, almost like a sentinel, allows us to reshape the global trial. So we're very eager to see that data as we decide how broadly we take sac-TMT and whether or not the combination partner should be a PD-1 or something else.

Let's maybe unpack the -- another big theme coming out of ASCO, which you were very much at the center of as well, which is the progress on the PD-1-VEGF bispecific class. So I guess, first, Dean, externally on the HARMONi-6 data that you saw from Akeso. I'd just love to get your thoughts on the issues that were raised by the discussant on the stage after the data was presented that fueled some substantial discussion and debate among investors. I mean, are these really substantial concerns around this global translatability in terms of differences and age? Or is this just skeptics trying to poke holes in the data?

So I think everything the discussant said is legitimate, and we take them seriously. I think the person who spoke was very clear of the things one has to think through. But just stepping back, one of the things that's been very clear when you add PD-1 and VEGF, whatever the VEGF part has been, has been you can hit PFS, but it's been hard to hit OS. That's been a constant sort of theme. We've seen it in our own pipeline. Other people have seen it in their pipeline as well. But you need to step back and sit there and say, is this a clean PFS to OS? You'd have to say that it's clean in relationship to the OS appear to hold.

There are all the other caveats that one has to think about. And so one has to be very thoughtful how one advances it. And so when we look at that data, we sit there and go, on one hand, there haven't been many things that have translated into PFS and OS, and this one is. So we do not -- we think that's an important contribution. But I think the caveats that the discussant said, informs us as to how do we think to move it forward and in what partner should we move it forward and in precisely what indications we would move it forward.

Clearly, if you look at PD-1s and VEGFs, there are opportunities in lung, but it's not just in lung. It's an HCC, it's an RCC, it's in cervical, it's in ovarian. There's many places where a PD-1 and a VEGF works. So we're doing the hard work to sort of sort out where and when we should target those different indications. But equally important for us is not just where we put the PD-1, VEGF, but what's the combination partner? Should it be chemo, should it be Sac-TMT, should it be a different ADC, should it be a different molecule.

So let's unpack that a little bit more. At ASCO, just regarding your own PD-1-VEGF program that you alluded to a little bit right now. You noted that it was Phase III ready, which was intriguing and suggest it's moving potentially at a more rapid speed than certainly, I think a lot of us had thought. So I guess we'll just ask the question, like what data are you waiting for externally or internally before you get comfortable, in your words, to let the dogs out? I think you phrased it...

I'm going to have to live that one down a little bit. But...

What indications can be...

Yes. So clearly, we work extremely closely with Kelun. So us understanding where some of the other agents are will be really important because it's not just around the PD-1, VEGF. We believe that PD-1, VEGF could be an accelerant to other novel molecules, whether they're antibody drug conjugates, whether they're precision targeting.

So it is about PD-1, VEGF. There is more information that will be coming out. But equally important, it's the combination partner that you put in, in a specific tumor indication. So for example, you've talked about the OptiTROP. How that OptiTROP plays out will inform us as to when or whether we should -- how we would advance that sac-TMT in lung and who the IO partner would be.

Okay. Very clear. Another big theme out of ASCO that obviously got a lot of attention was RAS. And you discussed Merck's KRAS programs at your own ASCO event. So how do you see the applicability to lung cancer? And what are the tumor types you see rationale to target? And how is Merck approaching development very broadly?

Yes. So when you think about the RAS, you think of 2 major tumor types, there's many more. But you think of lung, you think of pancreas and you think of CRC. What we have the ambition to do is to displace KEYNOTE-189, not with a PD-L1 VEGF necessarily or Sac-TMT, but in those patients who have RAS mutations that you take a PD-1 and a RAS inhibitor and you don't take any chemo. And you see that in our G12C programs that are advancing, and there's many programs in relationship, not just in metastatic but earlier. We also believe that in CRC, it's very important. There, the combination partner is not PD-1, it's cetuximab. How well can your compound compete in that combination.

And then we've also said that we have a non-G12C RAS molecule, 4716, that one could imagine that whatever we see with our G12C, one would begin to replicate with our non-G12C in lung and CRC. We give enormous credit to RevMed. They've really made an important contribution for pancreas. I think many people will drive to pancreas, and we will make the decision when or whether to drive into pancreas, depending on how we look at where we can do the most good. I do think that many people will enter the field targeting pancreas given the important data of RevMed.

Okay. I have one more oncology question, and then we're going to keep moving because there's so much to talk about in the pipeline, which is a great thing, Rob, as you alluded to earlier.

Just at the ASCO event, Dean, you noted the historic nature of the INT program, partnered with Moderna. So just remind us on your technology, how the technology approach is differentiated there? What have you learned now in terms of what's been derisked in melanoma? And what's the path forward there as you look to expand into other indications and turning this asset into a scalable platform business?

Yes. So I have to give enormous credit to our partners. Previously, I talked about Kelun, but I must talk about Moderna. Their technology is differentiated. And the fundamental issue for cancer "vaccine" or individualized neoantigen therapy is people have done this for 30 to 40 years. And they've had to pick a single neoantigen. That's very difficult in solid tumor. What the Moderna technology allows us to do is to make a spread bet. We don't have to pick one. It's 20-plus, right? We can pick 30, and that's critically important. And so the ability to pick so many neoantigens and put it in a vaccine is important.

We have focused where IO has worked. We have focused where KEYTRUDA works. We have focused where KEYTRUDA works in earlier stage. And so that's where we are focused. And the melanoma data that we saw in Phase II, I think, is thought-provoking. And if we can repeat that in the Phase III, I think it will move the field in a substantial way.

One of the things that you also notice is that when you think about mRNA, sometimes people worry about durability. But for the melanoma, the 5-year data, I mean that's pretty durable, right? There was no more injections. It was pretty durable. That confidence led us to open up additional trials and even earlier stage in lung as well.

So as that moves forward, [Audio Gap] where you see KEYTRUDA at a minimum [Audio Gap] you could see us be very interested in moving INT in that form. We would also look at other people who are doing it in non-IO sensitive tumors and metastatic. And if they get positive readouts, we would react to that as well.

Okay. Let's keep moving. Dean, let's move to cardiometabolic. Enlicitide, just has the filing been made? And if not, what are the remaining gating factors? And you have this CNPV program. Any impact on that from Makary's departure?

Yes. So I can tell you that I actually had a meeting because after the Makary departure, the FDA wanted to make very clear to us this is on. And so we have every indication that the national priority voucher given for enlicitide is moving forward.

In relationship to how it's done, you -- it's almost like a rolling submission. And once they're satisfied, they send you a letter and then they say the PDUFA date is going to be this time. Whenever we receive that letter, that's when we will make it public. But now in the CNPV program, when you get that letter, that PDUFA date is really fast upon. It's no longer 6 months or 9 months. It could be within 2 months. So we believe that's moving forward, and we're very eager to move that.

And we think it's going to lower LDL in a substantial way. And the -- the point that I would also make out is the AHA and ACC has done a tremendous work in changing the guidelines. It used to be, hey, take a statin and call me later for the last 12, 13 years. And what they said is we're going to give you hard targets that you need to meet. And I think what that will do is it will increase the need for having patients not just on statins, but other mechanisms like PCSK9 and both the antibodies and our small molecule. I believe that the expansion will not be what percent of the PCSK market who gets. I think that there could be a substantial increase in the PCSK9 market.

And I guess as we think about the development of the enlicitide program more broadly and you think about combinations and particularly including with GLP-1s potentially, just what are you paying the most attention to in terms of market developments? And Rob, I actually want to bring you into this conversation as well to talk a little bit about just obesity and how strategic that is to you. So maybe starting with you.

So I would just say enlicitide is really important for that patient population. Clearly, GLPs are really important. I think people know that we have a GLP-1. We've been very focused on being very clear that we're not going to be playing in the peptide injectable or the peptide oral. We want to play in the small molecule GLP, and we want to play in the small molecule combination space. Those programs are moving very fast within our program, but in relationship to the markets of both obesity but also enlicitide. Rob?

Yes. No, I think Dean said it, I mean, we are interested in looking at the broader obesity space, but less about obesity than it is the comorbidities. So it is more broad in the way we think, and that's where the combination strategy comes in. And as he said, it is about oral small molecules and how we can combine that is the focus area.

So that's kind of where we're focusing. And you'll probably see more from us in that space coming out into the early 2030s. But there's a lot of work to be done with enlicitide in the interim period, not only as a mono agent, but also with our fixed-dose combination potentially in combination with Lp(a). So there's a much broader portfolio that we're thinking about across the broader cardiometabolic space.

Okay. Maybe just on WINREVAIR, Dean, just any update there, too, on FDA discussions on the Phase III trial design, feedback on time to clinical worsening as a primary endpoint and just timing on next updates there.

Yes. I don't want to get ahead of the FDA, but the time to clinical worsening to me is like really important. That's the most meaningful thing to the patient and to the provider. So I just want to make sure that to me has to be a prominent part.

I mean just to sort of step back in PAH, I think PAH, I think sotatercept/WINREVAIR and activin signaling inhibitors has changed how we talk about that field. And the question is, in a patient population that has HFpEF and has PH physiology, which is one of the hardest patient populations, can we make the same contribution. And so we're very eager to do that and move that forward with the FDA and increasingly with the community because they recognize in this patient population, they largely have nothing.

Okay. Let's maybe move to immunology, TL1A, tulisokibart, we're approaching the pivotal Phase III ulcerative colitis readout, I believe, in August, September. So I guess, how should we be thinking about the bar for that pivotal? What would constitute a positive trial? I mean your Phase II data set a really high bar already.

Yes. So I would just step back and what do we hope? What do we hope is that TLA -- TL1A, which is a member of the TNF superfamily gets talked about, no different than TNF is talked about, no different than IL-23. We want this to be a node that is really important. The second point that I want to make out is we think we want to make it not just a node because of its efficacy, but also because its AE profile is so low, so it opens up combinability. And the third thing that we think is really important is that we think that there's a narrative about immunofibrosis. Those other agents are really important and an important node, but they're not -- people view them as immunology agents, not fibrosis agents.

So although we're doing ulcerative colitis and Crohn's disease, what you see our clinical development is quite extensive. And in comparison to others, much more extensive. We have it in HS, we have it in psoriatic arthritis, we have it in rheumatoid arthritis, we have it in SSc-ILD. And we are hoping that as we see data from this, can those different indications make that concept of immunofibrosis come alive. And if it does, then it gives us a beachhead to expand, deepen and extend with other biomarkers and other combinations, all being different depending on what the indication is.

Okay. Maybe just moving on to your HIV program.

Thank you.

Do you want to comment on the data from yesterday? I'll leave that as an open-ended question for you.

So we're very pleased. We have talked about islatravir and that family as an NRTI next generation with translocation inhibition. But what we've always said is this could be a new anchor medicine. And you see it in isl-dor, which is a once a day with non-integrase, 2-drug regimen, first 2-drug regimen without an integrase. We're launching dor-isl. We have both naive as well as switch data. You have this isl-len now, q week. We have positive data. We'll be talking to the FDA with our partners, Gilead. They're the ones who have the market authorization, but this could be the first q-week treatment, a 2-drug q-week treatment with 2 novel mechanisms with no integrase.

And then you also have our own islatravir-ulo, which is, again, trying to show everyone islatravir can be that base. and another q week. And then the fourth thing is it's not islatravir, but it's islatravir like, MK-8527. Can we be the first compound that can make a prep that's q-month oral. I mean, to us, that's that excitement. So we laid out 4. One is getting launched, one, we have positive data and hopefully, 3, 4 fall into place as we hope.

I'm very excited about that program, too. It's great to see the enthusiasm. Let's talk about ophthalmology and retinal disease. You've got the BRUNELLO study is reading out the Phase IIIs in DME, I guess, third quarter, fourth quarter. So just level set us on how we should be thinking about the program because as I look across consensus models, there's not a lot reflected for that.

Yes. So I would just step back and say our ambition here is within the company, and Rob and I -- is palpable. What we're hoping to do is to put 2 mechanisms in retinal vascular disease, [Audio Gap] which is a Wnt agonist. And the concept is, could this be the [Audio Gap] vascular endothelial growth factor pathway molecule, an agonist that could treat in diabetic macular edema. So all the other sort of drugs in diabetic macular edema and age-related macular degeneration are vascular endothelial growth factor based. This would be the first non-VEGF.

The reason why that's important is that VEGFs have transformed the field, but there are many patients who don't respond well with VEGF immediately or with time. So we hope that we can be the first non-VEGF mechanism of action moving to that field.

But I also want to make sure that we also think that we want to be the best VEGF mechanism as well. So we have MK-8748. It is differentiated from Vabysmo in the fact that like Vabysmo, it has an anti-VEGF arm. But differentiated for VEGF, we have a component that agonizes, that activates Tie2, and we are very bullish about that. So what we're hoping to do is provide the retinal field, can we really have an excellent anti-VEGF offering in MK-8748 that is differentiated. And can we also provide them with the first non-VEGF pathway in MK-3000. If we can do both of those, then we believe that we can actually advance this field. And I think Rob can speak about the commercial. When you look at the commercial opportunity in eye, it's not insubstantial.

Yes. I mean it's worth pointing out just to kind of size this between DME and AMD, it's about a $15 billion market. As Dean said, 40% of patients will either -- show today either partial or no response to VEGF therapy. So there's a lot of switching that happens in this space, a lot of unmet need. And if we have now 2 agents that can [Audio Gap] we think that's a meaningful opportunity. We're talking about the Wnt, which we will see positive -- or we will see the data readouts coming. But we also accelerated our Tie2 into Phase III faster than people had expected. That's moving now in AMD. So you've got now our Tie2 moving in AMD. We've got the Wnt moving in DME. And so our ability to have a meaningful impact, probably bigger than people expect and sooner than people expect, is real.

Great. Great to see the progress in that program, too. I guess in the last couple of minutes, quick maybe rapid-fire, Dean, what's in the invisible pipeline that Rob talked about that excites you the most?

I think it's invisible. But I would just sit there, I go, you look at our pipeline, we are laying out new beachheads. And when we think about those beachheads, we can expand, deepen and extend. There becomes incredible opportunity to add on other mechanisms to the ones that are in the visible pipeline. So much of it is this.

But I'll just lay out at ASCO, I, for example, for antibody drug conjugates, everyone was so focused on Sac-TMT. I need to remind them, I've got 3 with Daiichi Sankyo. But the other thing is I've got one in heme, and I've got like 4 or 5 heme assets moving, maybe 3 of them with readouts in '28, '29. And also, we laid out there, there's like 2 or 3 other Kelun antibody drug conjugates that we haven't declared that will be very important as we, with Kelun, decide when to make that reveal depending on their data and our data. So there's a lot, but some of the "invisible" is kind of visible. It was on a chart at ASCO.

Great. Great framing. Rob, any closing comments in the last few minutes?

No. I think the hardest thing here is the -- we have so many opportunities. The breadth of our pipeline is so impressive, not only in the late phase, greater than 20 assets driving over $70 billion, all either now launching or will be launching very soon. 70% will be completely derisked by the time we get to 2027 from a clinical perspective. But we have an equally exciting Phase I pipeline as well. You can think about macrocyclic peptides, you can think about antibody drug conjugates and others. So our sustainability as a growth engine is real, and you're going to see it increasingly play itself out as it already has through the proof points we put on the board so far.

Well, great to see all the progress. Thank you so much as always for being with us. I really appreciate the update.

Great. Thank you.

Good morning, everyone. My name is Akash Tewari. I head our pharma and biotech efforts here on the research side for Jefferies. Joining us is Merck, a company that really global company with focus on multiple disease areas. But we have Marjorie, who heads their oncology efforts, and Merck is certainly a leader there, and we're fresh from coming from ASCO. So I'm really excited for this conversation.

Marjorie, maybe I'll hand it off to you for some opening remarks, and we'll get to going.

Yes. No, great. Thanks so much. ASCO was an exciting time for Merck and for us. Our partners, Kelun Biotech presented data from OptiTROP-Lung05, which is a Phase III global study looking in non-small cell lung cancer at the combination of sac-TMT combined with KEYTRUDA versus KEYTRUDA alone, showing clinically meaningful improvements in progression-free survival and a trend noting immature data and overall survival for those people who had non-small cell lung cancer with a TPS of greater than 1%. We also had updated data sets from KEYNOTE-942, which is a combination of pembrolizumab and INT, an individualized neoantigen therapy as treatment of people with certain melanoma Stage II and III, and that 5-year durability data was quite compelling.

We also had compelling data from the 5-year update from KEYNOTE-522, looking at people who have triple receptor-negative breast cancer as well as other updates across the oncology portfolio. So it's a great meeting for Merck. And there was a lot of really exciting external data as well, which made it on time and helps us to be excited about our continued path forward.

Understood. And I certainly agree. It was definitely a good ASCO for Merck. I wanted to start on lung, and I'll take it from a different angle, which is the question we often get from investors, and frankly, I've asked on investor calls as well. Why hasn't every study in lung started yet? And I can sense that your team has been consistently very diligent, and you mentioned data-driven, I think that's right. But there's a dynamic on this, which I don't think is well appreciated, which is pembro in lung may actually end up having a much more diversified revenue stream than I think people appreciate. People think about KEYNOTE-189 as a massive driver, but you guys have run adjuvant studies and maintenance studies. And so this idea that frontline lung in that traditional sense is the be all and all may not actually end up being the case. Could you give some color on that in terms of when we think about pembro's revenue drivers today in lung, how diversified is it in the United States?

Yes. I am not the best person to speak to this. So I apologize already, but I should have these numbers, and I do not. It is not the #1 revenue generator for Merck. I can't speak to where that comes from. But you're right, we now have multiple studies in the adjuvant setting, including 6 that have overall survival and more of the revenue, particularly future-looking revenue coming from KEYTRUDA Qlex and we anticipate in those settings, less so with the 189 regimen.

Understood. Now maybe going into ASCO and I'd love to give -- you obviously have a PD-1/VEGF in development that's Phase II-ready. And your team has been very prudent in terms of where you want to develop that asset. But I'd love to get your take because you've said, we want to get more data from the field externally before we figure out our own development program. Obviously, we've got some important data sets from HARMONi-6, the ROSETTA data from BioNTech and then also the lack of a PFS on HARMONi-3. How is Merck's view on where PD-1/VEGFs fit a role, particularly in lung, changed post-ASCO?

This is such an interesting development for all of us as we think about how to optimize therapy for people with different kinds of malignancies. Through the KEYTRUDA program, we have more than 20 studies that we have done with different combinations of KEYTRUDA with VEGF inhibitors, including bevacizumab, where we have 2 approvals, lenvatinib, where we've seen some compelling data in endometrial cancer as well as in renal cell, and other VEGF TKIs. And so we've learned a great deal about the combinations over time. And historically, it's not been a one-size-fits-all approach for these kinds of combinations.

And what has really been the question, and I think people are more excited after ASCO is could the bispecific of putting these 2 together and potentially improving the therapeutic index by putting them together because the safety appears to be a little more tolerable and maybe you can increase the efficacy actually of the PD-1 as well by the structure. Is that going to be what it takes to open up VEGF more broadly across multiple tumor types.

And I think we're still left with more questions than answers. So HARMONi-6 was great data. I want to congratulate Akeso, the investigators. It is clinically compelling information. It's the first Phase III randomized data set we've seen with the bispecific that shows consistency between PFS and OS. But open questions remain regarding the translatability into global studies, the translatability into different subsets of non-small cell lung cancer, referring back to what you said with you even look at HARMONi and you look at HARMONi-2, where you didn't necessarily see that same correlation between PFS and OS.

There are also open questions about -- in that particular HARMONi-6 study about the differences in age that was seen, where you saw most of the benefit for those people who were less than 65. And in a different magnitude, people keep talking about 407 and KEYNOTE-407. And I'd like to point out that, that study, the control arm, there was 60% crossover. I don't know if people remember that, 60% of the control arm crossed over to pembrolizumab. And the age hazard ratios, there was a small difference, definitely between those who were less than 65 and those who are older, but the magnitude of difference was not the same that was seen in HARMONi-6.

And so I'm excited because the curves separated and they stayed separated. Will they continue that way? I don't know the answer to that. When we look at the HARMONi -- HARMONi-2. They didn't seem to do that from the data we know to date. So I'm curious, and it's an area where we want to continue to develop and explore. But how these agents will combine in different tumor types is to be determined. So we're always -- as you said, we're data-driven. We're very disciplined, and we will go where there's opportunity where we think the science and the clinical need makes sense.

Great answer. And there's a few threads I want to kind of pull on. I mean, a, you mentioned in 407 because I think there is this perception, well, squamous is slightly easier than non-squamous. But you mentioned there's a lot of -- there was actually a lot of crossover in the 407 study. So maybe just generally, this idea that pembro chemo in non-squamous versus pembro chemo and squamous, there's a difference in terms of how difficult it would be to beat that regimen. It sounds like you're saying that's not actually the case. Both are going to be equally difficult to surpass. Is that maybe the right?

I think that people -- KEYNOTE-189 has set a really high bar, and that's great news for patients. It's set a very high bar. And the other thing that we know is over time, clinicians get better and better at keeping people on therapies as they learn how to identify who best benefits from treatment, how to modulate side effects, so dose intensity gets better. It's doing a really good job for patients. There's still a huge unmet need, so you want to develop things. I don't know that I would say that it's -- the bar is different as a barrier to entry for squamous versus non-squamous. They're different biologic subtypes.

Generally, the effects are somewhat similar for a checkpoint inhibitor between the 2 histologies, the huge meta-analyses. There are more neoantigens in squamous, and so you might get a little more robust response there. So that may be why you're seeing the barrier to entry. The other aspect is that non-squamous, there's more division of that histology into subgroups such as RAS mutations are more present in those who have adenocarcinomas. And so it's more about how does the biology and the current therapy and thinking where the future is going, how then do you want to develop in these different spaces. And so again, we still have more questions than we actually have answers at this time.

Understood. Now one of the data sets that I think I sense is going to be incredibly important. I'm curious if you share the view is I think Kelun has an 06 trial with sac-TMT in less than 1% NSCLC. You got the 1% to 49% data from 05. And my view was it did look incredibly strong. But it sounds like the less than 1% is an important part of that puzzle. Why is that, right? What are you going to learn from that 06 trial and you're hoping to see with sac-TMT and NSCLC?

There are a couple of questions there. The first question is related to does the PD-L1 expression level have any influence on the activity of sac-TMT. And there's not a biologic reason to expect that to happen. I think is when you look at high PD-L1 expression tumor scores, that KEYTRUDA does better and better and other checkpoint inhibitors improve their activity as you get higher PD-L1 expression. And so the bar to beat and improve upon that is higher. So the magnitude of benefit tends to be a little bit less.

The question that is going to come from this is related to can you increase the benefit of the combination there where people do use KEYTRUDA for the less than 1%, but it's not uniform. And we have a lot of data showing that there is benefit in this population. So can you enhance that from an ADC combination. I think is one of the questions. We've seen some suggestions on tumor receptor-negative breast cancer that, that could happen that using an antibody drug conjugate. We've seen it in bladder cancer as well with a different antibody drug conjugate class. And so that to me is the question that I'm most curious about is, do you think that you can get something that is at least additive, if not better, by that combination? And that's what I'm hoping to see.

That is a fascinating answer because I will say, even talking to Kelun, they strongly believe that there is an inherent synergy between pembro and sac-TMT. And then there's also this dynamic of versus just traditional chemotherapy, you have a better durability of effect. So that's quite interesting, which kind of leads me to another perspective, which is KEYNOTE-189 was such a transformative trial because not only did you give great patient outcomes, but it was also the simplicity. I mean there's no QCS, there's no TMB. This is something that every doctor, it's histology, people understand this, and it can get used.

And you've talked about this concept of workhorse regimens. What's interesting to me is when I look at the OptiTROP-Lung05 data, I see a consistency of response. When I asked you about less than 1%, you're saying, I hope I see a consistency of response. And when I even look at the development strategy you had with Kelun, a lot of times, you ran studies in subpopulations, but you're ultimately actually running trials pretty much everywhere.

So to me, the read is actually we went conservative, but then we're seeing this drug is actually working more broadly. So that kind of brings me to ultimately what your strategy could be in lung. Could it be that it's not separate trials in different sub-cohorts, but it actually could be another KEYNOTE-189 regimen where whether it's a PD-1 VEGF or pembro that you could have a broad-based improvement across lines of therapy, and that's really ultimately where this is headed. I'm curious.

When we started the global program with sac-TMT, we tried to think ahead 3 to 5 years from starting these Phase IIIs, what was the therapeutic landscape going to look like? What was the clinical unmet need and where could we add the greatest value? And that explains where we are today. So for those who normally get pembrolizumab as a monotherapy, often these are older people who are not healthy, you don't want to give them chemotherapy for very specific reasons, sac-TMT is a cytotoxic therapy. It's an antibody drug conjugate, but it still has cytotoxic activity. So can you improve the efficacy because people unfortunately relapse and die in that population because they have metastatic disease, and so can that help? So that's that study.

The KEYNOTE-189 regimen, when you look at, you've got people who have squamous carcinoma and the biggest unmet need we saw was for a maintenance approach there. There isn't a maintenance therapy. There are different ways you could consider that population. It was you could add on to chemotherapy and KEYTRUDA, and often you compromise on the chemotherapy dose or the antibody drug conjugate dose or both, where the benefit is probably from the maintenance approach and that also can make it more tolerable. So we think sac-TMT is a tolerable regimen that could be given for long periods of time in combination with KEYTRUDA.

And then when you think about the adenocarcinoma population, we were thinking ahead, we knew that RAS was coming into this space. That segment is getting more and more subdivided. I think that the data from OptiTROP-Lung05 and then like you said, for 06 does raise the question of, is there the possibility that you will see some kind of sac-TMT combination across all of these subgroups. And so we don't have studies that we've talked about fully in all of the different populations. But I think we've got a very diverse portfolio, and you can look at the data from ASCO and you can make your own estimates about what we might do there.

Understood. Maybe just ending on sac-TMT, and you mentioned something that I think is incredibly important is it's a tolerable drug. And one of the things that I noticed with the 05 data was that the duration on treatment, which is to me incredibly important, was double that of pembro monotherapy, which is unusual. Usually, you wouldn't think the more cytotoxic combo regimen has that.

So a couple of things. Can you talk about really how you optimize the dose of sac-TMT and Kelun to their credit, too, when they started at 5 and 5.5 to then going to 4 , which seems like a Goldilocks dose, how you guys have learned to keep patients on therapy? How much of an improvement have you seen even from the early studies with sac-TMT to now the trials are running now? And how you expect that to translate into your own global Phase IIIs? Should we expect this durability of response to carry out that might actually be even better than some of the early trials we've seen out of China?

There's a lot wrapped up in that question. So let me think about how to approach this. From the dosing perspective, antibody drug conjugates, they do have cytotoxic payloads. And so there is usually a dose response you see with chemotherapy. And so you do see this with sac-TMT is that the higher the dose, you tend to get increased efficacy. You also get increasing toxicity, too. So we're trying to look for that best optimal activity versus tolerability when we were choosing doses. We also wanted to have one dose for combination as well as monotherapy. And we have multiple studies where we're using sac-TMT as maintenance.

And so going with the highest dose that is tolerable doesn't always make sense in combinations because combinations increase toxicity. They always do, whether it's a KEYTRUDA combination or any other kind of combination, side effects get worse. And the PK between 5 milligrams per kilogram and 4 milligrams per kilogram heavily overlap. And so it's the totality of data, and we see very consistent sort of durations of response, PFS in the Phase I and Phase II data sets that led us to choosing this. And that's why you saw 4 milligrams per kilogram combined with pembrolizumab in the OptiTROP-Lung05 study. So that's how we ended up with the dosing regimen that we so thinking about this is I'm not going to call it a workhorse or I'm going to call it a cornerstone ADC is that for the clinicians out there, having one dose and monitoring combination makes their lives a lot easier. It really does. And so that way, you don't have to think about it is in your pathways. You don't have to really question it. You just can't prescribe it.

The AE management, I talked about this in regards to 189. Doctors get better managing toxicities over time. And the opportunity we had here with our partnership with Helen is they were running studies ahead of us. And so we could learn from what they were doing. So an example of this is stomatitis care. TROP2 is expressed in the intestine. All of the TROP2 ADCs have some GI toxicity. And for an example, in the Kelun studies, they do not routinely use steroid mouthwashes. We use them in our Phase III data sets, and we have increased the use of it. We also use much more aggressive secondary growth factor prophylaxis because of the hematologic toxicity, and it also helps recovery of the intestine. And so we've been much more prescriptive about that. And these are AE managements that oncologists are very used to giving in their daily practice and don't add significant burden to patients.

So if you're able to make the experience tolerable, then that's where you get the benefit. How this will translate in global studies is to be determined. Global studies inherently are different than single region studies, whether they're China studies or a U.S.-only study. There's going to be variability there. And so we are teaching physicians in real time as they are getting used to these drugs. And so my hope is we have learned a great deal, thanks to our partnership and our very large Phase I/II program that we've done to date, and we continue to iterate and evolve what we're doing in Phase III programs. I'm encouraged by the endometrial readout, which you haven't seen the data yet, I have, very exciting. And so having positive PFS and OS is the first ADC in a Phase III data set endometrial, I think, supports that we are on the right path.

Understood. Now last one on just PD-1/VEGF and then I actually want to go broader. The [ Lenvima ] asset, I think the term Merck adopted was we're Phase III ready at ASCO. I will say the one question I think I've certainly thought of, and I've heard this from investors as well is like it's unusual for Merck to present unconfirmed responses. I mean you guys are very straight and narrow. You give confirmed responses, you give proper durability. And at AACR, I think both in the poster and in the abstract, it was kind of the same data cutoff.

And so the question I've always had is really how did that data mature over time? Really encouraging 55% response rate, but it was unconfirmed. Is there any qualitative color you can give us in terms of as you've given that therapy for longer duration because that's really what you have internally, how that profile has evolved over time?

I don't like to talk about data that's not public yet in any kind of form. And so we have confidence in the data that we presented. Otherwise, you wouldn't have seen us present information like that. And so we wouldn't call an asset Phase III ready unless we thought that what you would see is what you would get.

Understood. That's helpful in and of itself. Now maybe stepping back and hitting on also CML. And you guys just did some external BD there. I was happy. I actually, I covered Terns. So it's always great. But there's been -- I think to me, it has been kind of frustrating because there's this idea like, oh, I read the deal documents and the response rate changed and this is not the asset we think it is. And I'd love to give you an opportunity to kind of -- what is your perspective when you saw the 701 molecule in terms of, a, safety and durability of response. But b, I really want to hit on efficacy, right? I remember talking with Amy at Terns and she was saying, we have the opportunity to maybe run a head-to-head study against Scemblix or run a study that where we feel like we could be superior against standard of care, which is something Scemblix never showed. So specifically on the efficacy front, what is your view of that molecule and what it can deliver?

We're really excited about the acquisition of Terns and TERN-701, which I think we've now renamed MK-4208, but we're calling it 7013. And this drug, we really appreciated that we think that they have improved the therapeutic index. And that's -- it's -- the way that they have presented data is very consistent. When you look back at the original Scemblix Phase II data sets and Phase I data sets and the other second-generation TKIs, they use the same terminology. So that way was an apples-and-apples indirect -- so that's where the data set is. We were able in diligence to look at patient level data and look at every single patient, including the ones that weren't presented at ASH last year and look broader. And so when we made the statements that the efficacy, you've got incredibly fast kinetics of time to response.

We were able to independently verify and look at each patient and verify that. When we say that MMR is around 2x what you would expect to see from more recent assets. We have verified that information and DMR 2 to 3x similar direct comparisons, again, all of the caveats and limitations there. All of that is very accurate information. And so we think this is something that is -- does have the opportunity, as Amy had said, when she was CEO of the company, of being able to really improve outcomes, not only in this sort of relapsed/refractory population where it's originally studied, but I think a lot about the first-line setting because clinicians still worry.

Thankfully, the transformation in acute leukemia has dropped dramatically. And so it's less than about 10% right now. It's really come down. But what you want to see is that very fast response. They do get better over time. I think there was updated data presented at ASCO on Scemblix that's showing over time, things get better. But you really want that deep, deep response and then you want the durability of it because it opens up the potential for potential for some people to go off therapy. And this is a chronic disease. And after several years of therapy, if you keep someone very suppressed, you might be able to stop their therapy and give them a break.

This goes into the tolerability as well is that most of the significant toxicities that have been reported in this class have occurred in the first 6 months. And so I think that, that's definitely there are class effect side effects that you are going to see that all of them are going to have. But it's the magnitude of them, the frequency and how you manage it that improves that therapeutic index. And I think Terns has done a really nice job there. So we're excited. We're continuing on with the program and the progress. We're about a month into the acquisition and the integration, and we really are excited about the potential opportunity in the future with this asset.

Understood. And maybe just a final point on that. In terms of the design, I know it's early in terms of a Phase III. I think quite an important part about deep molecular response and that could be curative. Could you run head-to-head studies? Could you run or a trial where it's more traditional to what Scemblix did, which is in kind of frontline against standard of care. Is there a discussion internally for your team to take the more aggressive approach? Or will more traditional.

So we're some month in. So give us a little time.

That makes sense. Now maybe stepping back, the ADCs you don't get asked a lot about are the Daiichi ones. And that at the time...

Because they're great.

Okay. So -- and that's incredibly important because, again, one of the largest pharma partnerships ever, I think probably the largest at the time of the deal. But I think there's been mixed headlines. There's -- it's a really competitive landscape. And there's always this question of, well, which one of these assets is Merck right now most excited about. I'd love to kind of give you a chance to refresh in terms of the data that you have internally because you're running these kind of dynamic Phase II/III trials, larger Phase II studies. So there's a lot of data you have internally that maybe is not public yet. Of the 3 assets, which one do you feel like since you've acquired it, you've gotten much more excited about as you've gotten more clinical data?

This is always hard because it's like asking what your favorite child is or -- so what is it that you like to do? The IR team will laugh because if i get asked a question, I always like to mention one specific drug is my favorite drug because they're also different and special. They each have fantastic potential. And that's what I think is -- we saw that initially when we did the diligence and we started initial discussions.

And as we're seeing data come out, if you look at I-DXd, we've got a PDUFA date in October for small cell lung cancer, where there's tremendous unmet need, about 4% survival at 5 years for this horrible malignancy and very compelling efficacy from the Phase II data set, we have ongoing Phase III study and potential for combinations also with MK-6070, which is our DLL3. We have ongoing Phase III studies looking at I-DXd in esophageal cancer as well as in prostate cancer, which they're all exciting to me. And I think the continued data that we're seeing keeps me excited about this asset and the potential. And we have other Phase II studies ongoing, which we've not publicly disclosed.

If I move to R-DXd, another one where it's, again, exciting and compelling data. It is -- you see very marked responses in platinum-resistant ovarian cancer. So we have Phase III studies ongoing in the platinum-resistant setting. We have large Phase II data sets and more Phase IIIs soon to follow in this indication. We are also looking at R-DXd in other tumor types. And so we're waiting for emerging data to help inform where else this drug could potentially go.

And then with P-DXd, we started a Phase III in breast cancer. And so HER3 is really important in breast cancer in a way but I think is not always appreciated. And so we've started one where in hormone receptor positive breast cancer, including a combination with KEYTRUDA, where normally you don't give KEYTRUDA. And it's partly what you mentioned earlier about the ADC combination, -- can it improve the likelihood of benefit to a checkpoint inhibitor because of increased antigen exposure. Is there something there that makes that happen?

And with this, we also -- in the study, in HER2 is allowed in the control arm because it does have very, very, very low HER2 levels in there, and we know that there is expression response with ADCs generally across the board. We also are doing Phase II studies, and this is public information, looking at HER2-positive because HER3 is particularly important in HER2-positive disease. And HER2 has done an amazing job. I'm a former breast oncologist, I'm now drug developer. And for me as a breast oncologist, HER2 has been transformative in HER2-positive disease, but there's still a ton of unmet need and people diagnosed with de novo breast cancer. So opportunities for multiple different kind of combinations to innovate there.

And a quick one on that, de novo. I mean, this question, I think Lilly presented some data with her Nectin-4. And there's -- to me, this is like -- this is a huge problem. You have all these TOPO ADCs. They're all going frontline. You're going to have this issue in ovarian. And I think there is early signs that if you retreated with TOPO, you're not getting a response at all. It is regardless of even changing the target. So when you talk about HER3 for breast, is that -- what's your confidence that you can retreat with the topotoxin and get a response? Or is it more we're trying to go to populations where Enhertu really hasn't gone?

I think to be determined. And so there are multiple different data sets. It's -- well, if I take a step back and just talk about chemotherapy, and so I'll go back to my history as a breast oncologist, we even would never treat someone with paclitaxel to go to docetaxel. We would never treat someone with Adriamycin to go to Doxil. You don't do them sequentially like that. And so there have been data sets presented that have shown that if you do ADC A with the TOPO and the ADC B with the TOPO, you don't see a lot of activity. That doesn't surprise me.

The big question is at what treatment-free interval do you get sensitivity back and does that happen? Because you can retreat with taxanes in breast cancer if you have a period of time between them and get quite robust activity. Same thing is true with anthracyclines. You can retreat with Doxil if you had Adriamycin and get quite robust activity. So I think it's to be determined. If the mechanisms of resistance are different with the TOPOs, you can get topoisomerase 1 mutations and you also can get change in efflux pumps. And probably, it may be that specific TOPO payload that could make a difference on whether or not there's response to. So a lot for us to learn and think about moving forward.

Understood. I have a little break on my next meeting, so I'm selfishly going to ask one more question. She's giving me a scalp, but it's fine. On the Moderna INT partnership, and I say this is -- I'm probably -- I was more skeptical than anyone else. I was like, there's all these LAG-3 studies in adjuvant and they've all failed actually. And you continue to present really interesting data regardless of PD-1 expression of a durable response, which I think is quite interesting. I want you to talk about the signal you've seen in melanoma and how it might apply to lung. Have you -- has your confidence in that program increased? And what are you learning about the biology of these personalized cancer vaccines that maybe we don't appreciate?

So for those who are not familiar, 942 is a study looking in Stage II and III melanoma of pembrolizumab versus pembrolizumab combined with INT, 5-year follow-up information, you saw that there is almost a 50% reduction of distant metastasis as well as relapse-free survival. So I'm rounding up one number rounding down another number. So really compelling activity that's prolonged. They also have exploratory data showing T cell clonal expansion that was maintained even though the INT was stopped and it wasn't continued on, no boosters were given.

So the question that you're asking is how do we take that and apply it to non-small cell lung cancer. The reason why we started Phase III is we just opened up one in Stage I lung cancer -- non-small cell lung cancer relates to the TMB levels and the neoantigens, the similarities that you see between non-small cell lung cancer and melanoma. The underlying biology of what makes something immunosensitive is the most similar between these two diseases, which is why we started our Phase III programs. We have multiple Phase II studies looking more broadly, for example, renal cell, which is IO sensitive, has less neoantigens. And so will something like INT be effective there. And then other studies which are IO-sensitive like bladder cancer, we have Phase II studies ongoing to really understand that as well. So more to follow.

More to follow indeed. Thank you so much. I really do appreciate.

Thank you for standing by. Welcome to the Merck & Company Inc. New Jersey USA investor events at the American Society of Clinical Oncology Annual Meeting. [Operator Instructions] This call is being recorded. If you have any objections, you may disconnect at this time. I would now like to turn the call over to Mr. Peter Dannenbaum, Senior Vice President, Investor Relations. Sir, you may begin.

Thank you, Ivy, and good evening, everyone. Welcome to Merck's Investor event at the American Society of Clinical Oncology Annual Meeting. Thank you to all of you who've made the effort to be with us here in Chicago. It's great to see such a great crowd here tonight, and thank you for those that are tuning in via the webcast.

So we're excited to have this opportunity to speak to you about Merck's oncology program. During today's call, a slide presentation will accompany our speakers' prepared remarks and has been posted to the Investor Relations section of Merck's website.

Before we get started, we'd like to remind you that some of the statements that we make during today's call may be considered forward-looking statements within the meaning of the safe harbor provision of the U.S. Private Securities Litigation Reform Act of 1995. Such statements are made based on the current beliefs of our company's management and are subject to significant risks and uncertainties. If our underlying assumptions prove inaccurate or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements. Please reference this slide in our presentation and our 2025 10-K, which identifies certain risk factors and cautionary statements.

So our agenda tonight will start with Dr. Dean Li, President, Merck Research Laboratories, who will make a few opening remarks. Dr. Marjorie Green, Senior Vice President and Head of Oncology, Global Clinical Development, will provide an overview of our oncology strategy and key progress across the portfolio, including important clinical data updates. Next, Jannie Oosthuizen, Executive Vice President and President, Oncology and MSD International will speak to the commercial landscape and the opportunity we see to further impact patient lives. Dean will then provide closing remarks before we get to Q&A. Sophie Opdyke is sitting here in the front row, Senior Vice President of Global Oncology Marketing, and she will also be available for Q&A.

So with that, I'd like to turn it over to Dean.

Good evening. It's a pleasure to see so many of you here in Chicago. One of the things, I think, is important is we're trying to create a cadence of what our strategy is and try to define what it is and hold ourselves to be predictable in saying that in 2021, we outlined 2 clear objectives: To sustain durable leadership in oncology, we wanted to maximize the positive impact of KEYTRUDA especially in earlier stages of disease; and to diversify our pipeline with novel mechanisms. And then since then, we have made steady and important progress in demonstrating the benefit of KEYTRUDA in improving patient outcomes, especially in the earlier-stage setting. Last year, we also introduced KEYTRUDA QLEX, a subcutaneous injection of pembrolizumab plus berahyaluronidase alfa, allowing the administration in as little as 1 minute when given every 3 weeks. And we have leveraged the data and insights gained from KEYTRUDA to advance a broad and diverse pipeline of innovative candidates and novel mechanism of actions. And I think Marjorie will speak to a few of them, but we use our experience with KEYTRUDA and what it can combine with in how we look at these novel mechanism of actions. And we also look where KEYTRUDA doesn't work so well and where we want new mechanism of actions as well. And then over the course of the last few years, these 2 objectives have been our guiding principles. And this evening, you will see some significant progress we have made in executing against them.

So let me put our progress in context because where KEYTRUDA goes allows us to figure out where other things should go and gives us a leveraging point in relationship than that.

So KEYTRUDA has now received FDA approvals for 44 indications across 19 tumor types as well as 2 tumor-agnostic approvals, and clinical programs continue to generate evidence with the potential to further transform cancer care. In 2021, we also felt that our ambition would be that 25% of KEYTRUDA sales would transition to go much more in the earlier stage indication by the end of 2025, and we've achieved that ambition. That ambition is important as we think in the future about our pipeline, but also setting up were subcut KEYTRUDA can go, KEYTRUDA QLEX can go.

And so today, KEYTRUDA-based regimens have received FDA approval for 11 indications in the earlier setting, of which 6 studies have demonstrated an overall survival benefit -- the gold standard for oncology trials. So KEYTRUDA continues to raise the bar in treating earlier stages of disease and improving patient outcomes and laying a road map for us to follow.

We have advanced our foundational position with KEYTRUDA to create a diverse pipeline by executing on 3 pillars that we think is important. Immuno-oncology, and you've seen KEYTRUDA, we've talked about KEYTRUDA QLEX, but it is around PD-1 VEGF. It is around INT as well. Precision molecular targeting that many -- some of the programs that Marjorie and also a very robust tissue targeting candidates in the ADCs, both internally but also with robust partnerships with Daiichi Sankyo and especially with QLEX. In total, we now have approximately 60 Phase III oncology trials, of which 40 are across novel pipeline candidates including our suite of antibody drug conjugates, T cell engagers, small molecules and individualized neoantigen therapy. These diverse candidates are being developed as monotherapy as well as in combination with KEYTRUDA or KEYTRUDA QLEX. And the culmination of the late-phase studies is a result of years of disciplined pipeline diversification, both through internal discovery and strategic business development. We believe that we are well positioned to deliver a steady stream or cadence of meaningful data readout over the coming years and further the impact on patients with cancer.

And with that, I will turn it over to Marjorie.

Thank you so much, Dean. If you think about the portfolio and Dean set up how we think about drug development and the assets in our organization, we think about 3 pillars of biology. And we do that because of the underlying mechanisms of growth and resistance of different cancers and being able to have drugs that can target specific biological pillars, and they can be combined together.

So our immuno-oncology medicines are designed to stimulate anticancer immune responses. These include KEYTRUDA QLEX, our investigational INT candidate and our PD-1 VEGF bispecific. Precision-targeting agents are designed to impact pathways that can derive cancer growth. This includes caldorasib, our investigational KRAS G12C inhibitor, which recently received breakthrough therapy designation in the first-line non-small cell lung cancer setting; as well as several agents from our growing hematologic portfolio, which I'll further touch upon later in the presentation. Finally, tissue targeting, which includes antibody drug conjugates as well as T cell engagers. These are designed to target chemotherapy and immune cell activation to tumors while attempting to mitigate effects on normal tissues.

The reason we've organized around these goes directly to our strategy. And so to have the maximum benefit for patients and meeting the needs of these patients as well as clinicians and society is we know that the best outcomes in oncology how when you give multiple drugs together or are the different mechanisms resistance for the heterogeneity that exists in most cancers combinations have had the best outcomes long term. And we've seen that for many of our KEYTRUDA studies with multiple diseases and multiple combinations. And so we want multiple mechanisms to have the best benefit.

We also want to develop agents, therefore, that have single agent activity that are active in and of themselves and that are combinable because that will give us the best opportunity to help the most patients with a specific kind of malignancy or a subtype of a malignancy. And we can have diversified regimens also that potentially can go across multiple tumor types depending upon the targets and the mechanisms of action.

We also want to improve the therapeutic index of our medications. That is to be able to help a physician and a patient understand for a specific tumor that a person might have, is there a biomarker that could predict benefit of therapy because every time someone is treated, a physician can tell someone, we'll hear the odds that someone like you might benefit from a therapy. But knowing for that individual sitting in the chair in front of you, it's often very difficult. We're talking about statistics. And as a person who sees a physician, that's really uncomfortable place to be. So if we can develop targeted therapy diagnostics, that will be really helpful to find those patients most likely to respond.

And critically, we want to bring these drugs into earlier stages of disease, as Dean talked about with what we've done with KEYTRUDA. And it's because we can have the greatest impact there. We can help the most number of people with cancer if we can treat the disease as early as possible, whether it is in the first line or second line setting in a metastatic disease or if it's in the potentially curative setting in the adjuvant or perioperative space.

So we take these 3 pillars, and we created diversified regimens that can be delivered generally across multiple tumor types. And so I'm going to start the update with one of the drugs that can do just what I talked about, which is a sac-TMT. It is one of our broadest programs in our pipeline. This is an antibody drug conjugate that we brought in through our partnership with Kelun Biotech. It's a differentiated Trop-2 antibody drug conjugate with a belotecan-derived hopizomaras1 inhibitor payload.

What we're particularly excited about is the bifunctional linker technology that's proprietary and is quite unique for the Trop-2 ADCs that are currently in clinical studies. This linker is designed with the intent to maximize payload delivery due to its very stable irreversible connection to the antibody. This is intended to prevent the payload for breaking off the circulation. There is a pH-sensitive connection that ensures intracellular payload release in tumor cells. There also is the allowance of the structure for bystander effect. The stability of the linker also enables a drug-to-antibody ratio of somewhere between 7 to 8, we say 7.4 to be very precise. But it's a very -- for the stability of the linker, this is a very high DAR when you look at other antibody drug conjugates. And so based upon its design and the compelling data generated so far, by our partners at Kelum, this has the potential to be a cornerstone antibody drug conjugate across a variety of different cancers.

So one such data set was the data you've seen at ASCO this year from OptiTROP-Lung05. This is a Phase III study conducted by our partners in China. And the study enrolled people who have non-small cell lung cancer, it could have been an adenocarcinoma or squamous cell carcinoma, with expression of PD-L1, 1% or higher, locally advanced, better as inoperable or metastatic non-small cell disease. These are people who had no prior systemic antitumor therapy, and they were randomized to receive monotherapy pembrolizumab or the combination of sac-TMT and pembrolizumab. The combination of sac-TMT and pembrolizumab provided a clinically meaningful and statistically significant improvement in progression-free survival by blinded investigator, blinded central radiology review in the overall study population.

This benefit was very consistent across subgroups. We're including those who had PD-L1 high expression, those with lower PD-L1 expression, squamous histology, non-squamous histology, age across all of the different categories, there was consistent benefit. And the intent-to-treat population, noting that this is very immature follow-up at this time, there is an OS trend observed noting again, it's very immature. And so no definitive conclusions can be made about that data.

But it's really exciting. It is. And particularly, we consider other Phase III data sets coming out of China and similar populations. It helps to demonstrate the promise of sac-TMT combined with pembrolizumab in our global trophuse 007 program, particularly trophus 007, we are conducting for participants who have non-small cell lung cancer whose tumors have a TPS score of greater than 50%.

We have other global Phase III studies in non-small cell lung cancer underway. The OptiTROP-Lung05 study adds to the growing body of data generated by Kelun Phase III studies. You're now seeing multiple proof points across well-conducted, randomized clinical data sets in multiple tumor types, including lung and in breast cancer. Most recently, Kelun announced positive results from OptiTROP-Breast03 study in the first-line triple receptor negative breast cancer space a few weeks ago.

Many of these proof points tie directly into studies that we have ongoing in our global TroFuse program. It is this collaboration we have a Kelun that allows us to expand and go into so many tumor types with confidence.

Our TroFuse development program is broad, and we think it's differentiated. TROP2 is highly expressed across multiple tumor types. And we've designed Phase III studies in tumors where there's an opportunity for us to meaningfully impact cancer care either with a differentiated development profile or where we can be a first mover.

As you see, we are advancing studies across gynecologic, breast, lung, gastric and bladder cancer spanning from mid- to late line in some settings, but mostly in the earlier stages of disease. We are also pursuing maintenance regimens in several of our studies. And many of these indications, these are first-mover opportunities in the way that we have developed our Phase III program.

In keeping with our strategy to improve the therapeutic index of our assets, we have a robust biomarker strategy in place for sac-TMT. We have a broad development plan; not every tumor may benefit from enrichment. The data that we've seen with our biomarker development conducted during our extensive Phase I/II studies in collaboration with our partners in China, has guided the implementation of biomarkers into our Phase III program.

I'm very pleased to share that TroFuse-005 is the first positive global Phase III for sac-TMT that has been conducted by Merck. This study demonstrated a statistically significant and clinically meaningful improvement in both progression-free and overall survival of certain patients with endometrial cancer. This is the first TROP2 ADC to show improvement in overall survival and progression-free survival compared with chemotherapy in certain patients with advanced or recurrent endometrial cancer and is the first ADC to have randomized Phase III data in this setting.

Endometrial cancer is the sixth most common cancer in women and it's increasing in incidence. There's significant morbidity and mortality, particularly in late-line settings, and there is no standard of care in majority of patients whose cancer progresses despite the use of I-O therapy like KEYTRUDA and chemotherapy. This builds upon our expertise in the disease where we have 2 -- we have innovated with therapies, including with KEYTRUDA. And we're excited about these results. We will be talking to health authorities, and you'll see the data at an upcoming scientific presentation in the near future.

sac-TMT is one of the 8 antibody drug conjugates that we are excited about and having clinical development today. We have one of the largest and broadest ADC portfolios in late-stage development and covering important cancers. Our ADC pipeline brings a diversity of targets, bispecifics and linker payloads. This provides potential opportunities to improve outcomes for patients and create unique combinations.

Now I want to move on to another important part of our portfolio, which is MK-2010. In addition to building upon tissue targeting therapies such as sac-TMT, where over half of our studies are being done in combination with IO therapy with KEYTRUDA, we are also building out immuno-oncology with MK-2010, which is our PD-1 VEGF bispecific antibody.

We publicly presented data for the first time from a collaboration study that was initiated by LaNova, and this was presented at AACR this year. The study demonstrated clinically meaningful data for MK-2010 as treatment for certain patients with advanced non-small cell lung cancer. For those in the first-line treatment-naive setting, the unconfirmed objective response rate was 55% among 11 previously untreated patients with PD-L1 positive non-small cell lung cancer at the 20-milligram per kilogram dose.

And what I like to look at is the waterfall. The majority of patients show tumor control or shrinkage. The safety profile of MK-2010 is consistent with what's observed with this new class of assets and allows us to be able to develop this drug potentially both as monotherapy and importantly, in combination with other drugs in our portfolio. We believe we are uniquely advantaged to fully explore the potential of the PD-1 VEGF access. While KEYTRUDA is central to our experience, much of what we have learned comes from combining it with different therapies and different mechanisms of action, including VEGF inhibitors. Although we are not sharing specific development plans today, as Dean noted, we are operating from a position of strength given the breadth of the studies we've conducted across multiple therapeutic classes.

In addition to the external knowledge about VEGF inhibitors and as emerging data comes about bispecifics, we have meaningful experience of our own. We have conducted multiple studies of KEYTRUDA combined with VEGF inhibitors, including Avastin combinations that have led to approvals beyond our own experience with a portfolio of novel agents that offer combination opportunities oriented towards combinations of the future rather than adding on to today's current standard, including ADCs like sac-TMT. Together, our experience plus our portfolio provides a strong foundation as we plan MK-2010 development across multiple tumor types in a rapidly evolving oncology landscape.

So now let me turn to our innovative hematology portfolio. You have seen our recent announcement about the acquisition of Terns Pharmaceutical, which brings us TERN-701. This asset further expands the portfolio in hematology despite multiple approved tyrosine kinase inhibitor, significant unmet need remains for improved efficacy safety and convenience for certain patients with CML. The team at Terns did a fantastic job of developing a highly selective, potent oral allosteric BCR-able tyrosine kinase inhibitor designed to improve upon prior generation TKIs. It's high target selectivity potentially enables higher dosing while limiting side effects supporting improved therapeutic index.

In a Phase I study, TERN701 demonstrated major molecular responses that are approximately 2x and deep molecular responses that are approximately 2 to 3x of those approved -- those compared to approved TKIs and historical data sets. We are very excited about this asset and look forward to advancing it into late phase development.

With TERN 701, our hematologic oncology portfolio now includes 5 assets that may be used across a variety of different hematologic malignancies in keeping with what our strategy is for Merck Oncology. Nemtabrutinib is a potent noncovalent BTK inhibitor designed not only to bind reversibly to BTK. But it also had activity against other kinases and is designed to help prevent some of the common resistance mutations that occur with covalent BTK inhibitors.

Bomedemstat is an LSD1 inhibitor. This is a mechanistically exciting drug with potentially disease-modifying effects in chronic diseases like essential thrombocythemia and polycythemia vera.

Zolibertimab vedotin is a ROR1 ADC currently ongoing in Phase III trials in diffuse large B-cell lymphoma, including a head-to-head study against Polivy. We have seen activity in GCB and non-GCB tumor cells and diffuse large B-cell lymphoma. We also have seen activity of ZB both as monotherapy and combination, and we are excited about the progress of this program.

MK-1045 is a CD19 T-cell engager potential utility not only in ALL, but across other hematologic malignancies.

And then TERN 701 rounds out our portfolio.

So again, thinking back to our strategy, the same principles apply here. We have created and curated a hematology pipeline of drugs that have great potential as a single agent and combination.

And then finally, let me provide you a forward look at the readouts you can expect from our innovative pipeline. We're excited about the portfolio. We have assets with compelling activity that have led to approximately 60 Phase III studies in our late-stage portfolio. That excitement and commitment to patients is leading to a series of readouts you've already started to see starting with TroFuse-005 in endometrial cancer. And we have a PDUFA date in October for IDXD, an extensive stage small cell lung cancer. There is a steady cadence of readouts extending through '27, '28, '29 across 10 new assets, reflecting the diversity of the portfolio and the broad reach we have.

I will now turn it over to Jannie to talk about the commercial opportunity.

Thank you, Marjorie. It's a pleasure to be here I have the privilege of addressing you in my new role as President of our Oncology business unit and Human Health International markets at a time of significant progress across our oncology portfolio. Our dedicated teams have established a leading franchise around the world. We continue to execute with excellence across multiple tumor types, driving patient impact and access to our important cancer therapies in over 100 markets. We have reached more than 4 million patients worldwide with our oncology medicines. Our suite of oncology products is approved in 58 indications across 25 tumor types, including 2 tumor-agnostic indications.

This portfolio provides a strong foundation for the broad range of opportunities Dean and Marjorie outlined. Our research colleagues continue to deliver compelling clinical advances, and we are excited by the reach and competitive pipeline. Importantly, the commercial organization, both in the U.S. and globally, is in place to deliver on that opportunity and further improve outcomes for patients. Today, I'll focus on the near-term programs, we're advancing with the same discipline and urgency that help establish Merck as a leading oncology company. I'll close with our long-term commercial aspirations for our broad and diverse late-stage pipeline.

We remain confident in the outlook for KEYTRUDA, supported by continued momentum in earlier stage indications and ongoing strength in metastatic settings. Sales from early-stage indications represented more than 25% of total revenue in 2025 and are expected to increase further. Indications approved in the last year, including in certain head and neck, ovarian and -- bladder cancers will drive a large portion of growth. And there remains potential opportunity for additional new indications both in earlier stage and metastatic disease.

We have built a strong presence in GU and women's cancers underpinned by the robust data KEYTRUDA continues to generate. By 2028, we anticipate that roughly half of KEYTRUDA's revenue will come from women's cancers and GU, reflecting the breadth of our clinical program spanning TNBC, multiple gynecologic cancers, RCC and bladder cancer.

Our commitment to innovation and addressing the unique needs of patients and health care systems extends to KEYTRUDA QLEX, our subcutaneous pembrolizumab with berahyaluronidase alfa. The launch is off to a strong start. In the U.S., we have seen a good acceleration in adoption since the establishment of the permanent J code on April 1. The adoption rate exiting the first quarter was in the mid-single digits, supporting our confidence that we are on track to achieve 30% to 40% peak adoption by the end of 2027. As expected, the majority of adoption is in patients who are on monotherapy regimens or combinations with other oral therapies.

A recent U.S. label update includes data evaluating patients' preferences between subcutaneous administration of KEYTRUDA and IV KEYTRUDA. Results showed 65% of patients preferred KEYTRUDA QLEX over KEYTRUDA IV where the most common reason being less time spent in the clinic. Outside of the United States, we have received approvals in the EU and U.K. and some other markets. We have made good progress in certain markets and expect launches in additional markets later this year. We anticipate 30% to 40% peak adoption on average globally, with peak penetration varying by market. We continue to be pleased with the impact we are having on certain patients with RCC and other VHL-associated tumors with WELIREG. We look forward to launching 2 additional indications for WELIREG later this year. The first one is LITESPARK-022, the combination of WELIREG with KEYTRUDA in adjuvant RCC, and it has a PDUFA date of June 19 this year. This builds on the foundation set by KEYTRUDA monotherapy based on the KEYNOTE-564 study, and if approved, would be the potential first IO combination treatment option in the adjuvant RCC setting. The study demonstrated meaningful improvement in disease-free survival.

The second one is LITESPARK, the combination of WELIREG with LENVIMA in certain previously treated advanced RCC, and it has a PDUFA date of October 4 this year. This is the potential first and only HIF2 alpha inhibitor plus a VEGF TKI regimen for patients whose disease progressed following anti-PD-1, PD-L1 therapy, and a demonstrated superior PFS versus a modern TKI with improved duration of response.

With these new opportunities in RCC as well as the future potential in combination with zanzalitinib, we believe WELIREG has multibillion-dollar peak commercial potential.

Next is IDXD, our B7-H3-directed ADC in collaboration with Daiichi Sankyo. IDXD has the potential to address unmet need for patients starting in extensive stage small cell lung cancer. Small cell lung cancer is a deadly, rapidly progressive cancer with high unmet need and very poor prognosis. Approximately 10% to 15% of all lung cancers are small cell, and about 70% of patients are diagnosed with extensive-stage disease. Unfortunately, the 5-year survival rate remains just 4% for those with distant metastases.

The FDA has granted priority review for IDXD in certain adults with previously treated extensive stage small cell lung cancer and set a PDUFA date of October 10 this year. This marks an important step for this potential first-in-class therapy.

Beyond extensive stage small cell lung cancer, we have ongoing registrational trials in second-line esophageal squamous cell carcinoma and metastatic castration-resistant prostate cancer, which represents a much larger patient opportunity. We're also exploring the combination of IDXD with [ galgatamine ], our T cell engager, also in collaboration with Daiichi Sankyo in small cell lung cancer.

As Marjorie described, our development program for sac-TMT is extensive and primarily focused on populations where we aim to be first-in-class. We are also exploring opportunities where we will be competitively advantaged due to the differentiated clinical profile of sac-TMT. Here, we outline the patient opportunity for each -- for each potential indication. The breadth of this program underscores why we believe sac-TMT has the potential to be a cornerstone ADC across a variety of different cancers. sac-TMT is being evaluated in the broadest range of disease and treatment settings of any TROP2-directed ADC with studies across early to late-stage disease in more than 7 tumor types, representing up to approximately 200,000 patients in the U.S., EU and Japan.

Building on Marjorie's comments, I want to emphasize the significance of the TroFuse-005 results. Patients with metastatic endometrial cancer have a medium overall survival of less than 1 year after progression on platinum chemotherapy, and there is no standard of care for the majority of patients whose disease progresses following IO and chemotherapy. sac-TMT is the first and only TROP2 ADC to demonstrate an overall survival benefit in endometrial cancer compared to chemotherapy in these patients with advanced or recurrent endometrial cancer. An approval would further built on our deep expertise in gynecologic cancers, we already have multiple indications and reinforce sac-TMT's role as a potential transformational therapy in this space.

We are building from a strong foundation as we advance the next wave of oncology innovation. We continue to see greater than $25 billion in nonrisk-adjusted commercial opportunity from our oncology late-stage pipeline alone by the mid-2030s. Importantly, this does not include the recent acquisition of Terns Pharmaceuticals, which has multibillion [indiscernible] commercial potential on its own. Over the coming years, we have the opportunity to bring 14 new products to market for the treatment of cancer across more than 80 new indications. As our product mix diversifies, we expect to establish a meaningful presence in hematology, building on our leadership position today in solid tumors.

In summary, we are highly confident in our oncology position and believe our strong presence will extend well into the next decade. With that, I'll turn it over to Dean for closing remarks.

So thank you so much for your attention here. This evening, we spoke to how we have executed on our oncology strategy, building on our strong foundation with KEYTRUDA while advancing an increasingly diversified pipeline of oncology candidates. In total, as you've heard, we have approximately 60 ongoing Phase III trials at this moment. I would imagine more will be opened. The broad impact of KEYTRUDA right to road map for the future as we develop molecules spanning 3 pillars of biology, immuno-oncology, precision targeting as well as tissue targeting, especially with ADCs.

Now we're deploying these candidates with the goal of maximizing benefit risk and convenience to patients while providing exceptional value for payers. Hopefully, today's presentation has contextualized our strategy and how we prosecute clinical trials. We believe that we are in a strong position to further improve patient outcomes in oncology.

I just want to emphasize that we're here at ASCO, and we're focusing on diversifying in oncology. But we've also said in 2021 that not only do we need to diversify oncology, we have expanded in other therapeutic areas. And I just would emphasize the cadence of readouts that you've just shown, especially what Jannie showed in the last is happening in the other therapeutic areas as well, in cardiometabolic with WINREVAIR otovir and the potential approval of elicitide and the follow-on compounds that follow that in immunology with tolasocopart as well as other immunology assets moving forward, especially in ophthalmology, where we have 2 assets moving fast. And in HIV, we've increasingly shown islatravir as a backbone. So I think this concept of us diversifying and expanding our pipeline since 2021 is important and relevant, not just for oncology, but also across other therapeutic areas and spanning multiple modalities, including small molecules and vaccines, macrocyclic peptide and complex and conjugated biologics.

And with that, I will turn it over to Peter for questions and answers.

All right. Very happy to take your questions. If you could state your name and your firm when asking your question, that would be helpful. So maybe Chris Schott to start.

Great. Just maybe a 2-parter on VEGF PD-1. Maybe just first, if you can just provide some context of your view on the data we saw at this conference and how that informs your approach as you consider development programs for 2110.

And then just when we think about that development program, do you think we've had enough derisking of the mechanism where we should think about Merck running a broad set of studies in a wide range of indications similar to what you do with TROP2? Or is this an approach where we could think about maybe a more gradual approach? I'm just -- I know you're not disclosing it, but how to think about that.

Loss of clinical development speak to that Marjorie.

No, no. Thanks so much for the question. I think we are all eagerly awaiting the data presentation of the HARMONY 6 data. And I want to congratulate the investigators and so for running a well-conducted study. With this -- the impact it has is that -- I think it's increased excitement, but also has left a lot of questions still remaining. And that's what I think your question is getting at.

So what was impactful to see was that I think that the hazard ratio for PFS have been 0.6. And unlike the other VEGF checkpoint inhibitor historic studies of chemotherapy combining with IO VEGF, the hazard ratio here was very close to the PFS hazard ratio. And this would actually include HARMONY 2, which had both squamous and nonsquamous in there that hazard ratio that had a much larger drop than you saw here.

The other thing that stands out is the AE profile was what was expected generally for adding in another mechanism, chemotherapy plus a checkpoint inhibitor, now will have a little bit more toxicity than the chemotherapy alone or a checkpoint inhibitor alone. And then you're adding a VEGF inhibitor on top of that, albeit the therapeutic index for safety does appear to have improved a bit with this particular kind of structure and formatting.

So the AE profile is what's expected. It was tolerable, had low rates of discontinuations and no surprising adverse events were noted.

They were very careful in how they talked about patient selection for this because of the historical challenges Avastin had in this space. So particularly in talking about cavitation, about blood vessel involvement. There also was an age cap of over 75. And we know that this is not a disease squamous cell -- non-small cell lung cancer is not a disease of young people. It's a disease of people who have been smoking heavily in their life and often older. I think in the United States, the median age for this might be around 70.

So there -- and when you look at the hazard ratios, for both PFS and for OS, they are not comparable by age. So I think it's clinically compelling. The curves. There's -- they overlap, then they separate.

Open questions. Does this translate into an older population? What is the reason that you have differences in outcomes and robust sample sizes for those younger than 65 and those older. Is there an AE profile? What's going on there? Is this sort of a random chance? It's not known. And the median follow-up is before that really -- you don't know what the OS is going to end up being because of the amount of censoring. It's still fairly early. So are those curves going to stay apart? Or are they going to start to come back together with time? And that's always been this open question when you look historically at the majority of studies that have been conducted with VEGF inhibitors and checkpoint inhibitors in non-small cell lung cancer.

So I dissected it, and the question is sort of what does that mean. And I think what it shows is that there are likely situations where the PFS will translate into a clinically meaningful overall survival. I would like to see this replicated in a global study. There -- the Chinese investigators do an amazing job of running really clean studies. And so I want to see this in a global study and what the data will look like.

The other open questions, you still have heterogeneity results and other tumor types. As far as the -- even in non-small cell lung cancer, if you think about the different HARMONY studies and the shapes of the curves and the hazard ratios, they're not as consistent as this. So to me, that means that there's still open questions about, is this something that will truly unlock benefit everywhere you have seen a VEGF inhibitor work and a checkpoint inhibitor work. And I think the answer is still we don't know.

But this is a positive finding, I think, it's great for patients in China, as I discuss and said. And for us, we've always in all of our studies and everything we do, including our sac-TMT program, we have a disciplined and very data-driven development program. And so we use all of those studies that you saw us flash up looking at all of our knowledge about VEGF inhibitors and checkpoint inhibitor KEYTRUDA combinations, we look at the emerging data. And then we're also thinking about the future because we're very excited, for example, about the OptiTROP-Lung05 data. We're excited about our KRASG12C program. We're thinking about what therapy is going to be looking like in a couple of years, not what it looks like today as we're developing our plan. We have a Phase III-ready asset with MK 2010.

Daina?

Daina Graybosch from Leerink Partners. In the -- in Kelun's OptiTROP-Lung05, I thought sac-TMT plus pembro looked pretty competitive when you compared it indirectly the pembro plus platinum-based chemo, both in 407 and 189. And I wonder what's holding Merck back from starting a head-to-head study with sac-TMT versus 189 and 407 beyond maintenance for 407?

So I'm going to turn this to Marjorie, but I will comment about many of my interactions with many of you over the last 2 to 3 years. And I would just sit there and I just would remind that when we first moved in sac-TMT, I think many questions were asked of why are you coming in to TROP2 ADC when there's 2 ahead of you. And I think what we said there is we don't think all the TROP2 ADCs are the same, just like we don't think all the HER2 ADCs are the same.

I think the other sort of thing that were remarked to us is that we thought that if you could get it right, you could be first in lots of tumors outside of breast and lung. And I think the endometrial data suggests that, that may be possible.

Now the question is because people said, well, you guys blew this out in 17. I've actually gotten questions of why did you blow it out so much. And now I understand your question is, why aren't you blowing it out further? Is that what I understand?

So with that, I'll turn it over to Marjorie.

Yes. No, thanks for the question. And I said our strategy, we are always looking to where we think cancer therapy is going to be. And so thinking back to when we started our program, we recognized from data in 507 and 189 from emerging therapies, and just biologically, we know that lung cancer is not one disease. And there is going to be increasing fragmentation of non-small cell lung cancer, including those who are eligible for KEYNOTE-189. And so we tried to think about where could we add the greatest value, considering that those who have non-squamous cell lung cancer have -- often have the RAS mutations, and that's going to be more subdivided into different therapies. There was the biggest opportunity for those who had squamous carcinoma and needed something to help give them long durable remission. That's what's led to that program.

The other one, TroFuse 007 was based upon -- there are people who don't want to give chemotherapy necessarily to everyone because they're not certain it's going to add benefit and high expresser PD-L1 scores. And so we wanted to show that, yes, we could do that. And again, further help to characterize different opportunities for clinicians and patients of how you could use this drug.

We didn't have the OptiTROP-Lung05 data when we were designing our program. And so we get had to think about how is the clinical practice going to change and recognizing where peer companies were how do you want to develop.

The other thing to consider is that there can be approaches where you combine ADCs and chemotherapy together. So if you're going to do a 189 head-to-head and try and take these populations together and to sort of replace, it is that you want to ensure that you've got really robust efficacy and some people have taken, let's combine chemotherapy in the ADC together. And there is one potential replacement study that's out there. But the combinations of therapy, when you look at other ADC chemotherapy combinations and some of the ones done in lung cancer, the response rates have not increased, suggesting the benefit may actually be the maintenance approach.

So are you going to get more toxicity? Are you going to impact the doses of either the ADC or the chemotherapy by combining them together and then adding a checkpoint inhibitor. And so I think our maintenance approach is where we think the biggest benefit is going to be there from what we knew when we started that study.

I don't speak to the future too much because it's a highly competitive environment as Angus who's in the room talked about in his Veropharm article. But I do think that it is important for us to look at our portfolio and look at

[Audio Gap]

the data generated in China to what we get in the global study. And I think one of the things I'll say is someone who's worked on antibody drug conjugates in 3 different companies is they are fairly consistent when you look at response rate, duration response and that translates into overall survival often. And so I can't forecast, as Dean said, what the TroFuse-005 study looks like. You'll have to wait until we're presenting it publicly, but it's compelling data that we think that we were able to have confidence in from the Phase II data enough to start the Phase III.

Great. Thanks, Steve. Michael Yee.

Michael Yee from UBS. With sac-TMT, it would seem to me that, obviously, you have the potential to also combine with a PD-1 VEGF. To what extent are you generating data either with 2010 that you are observing? Or that your partner Kelun in China is also generating data with sac-TMT with other novel agents including other PD-1 VEGFs that could be generating data that you could be learning from?

Yes, it actually gets a little bit to -- I think it was Courtney's question, is when you ask us what future looks like, one of the things that we ask ourselves is what will the future look like for a PD-1 in relationship to sac-TMT. And so that's something that, clearly, has been on our minds and clearly on the minds of our partner, Kelun, as well. But with that, I'll just ask Marjorie any comments you wanted to make?

I think that we have not publicly talked about our plans of sac-TMT in 2010. And so I'm going to keep that to myself at this moment. The same thing, Kelun's got their own stuff that they're doing as well. And so there's no public information available this time. Stay tuned.

Great. Thanks, Michael. Maybe in the back, Trung.

Trung Huynh from UBS. So some of your VEGF PD-1 competitors, they're optimistic for PFS-based approvals in first-line lung cancer. If you have a look at all of your TroFuse lung studies, they use OS as the primary endpoint. Is there a mechanistic nuance here? Does the FDA view ADCs differently than IO bispecifics for approval just based on PFS?

And then does HARMONY 6 make you want to move faster? Slower? Or does it not change your Phase III development time lines for this class? I know you mentioned you're not going to share your development time lines, but could we be sat here next year knowing what that Phase III program is? Your peers are accelerating quickly.

I love how the questions come. What I'll first say about the FDA is the FDA in the fields have been reasonably consistent. OS is a really important endpoint. And I would just emphasize, it's not just important for the FDA and regulatory agents fees, the payer who's being asked to pay for antibody-drug conjugates over chemo, they have some say in this. And so we think it's very important to keep that in mind, but I don't know how you want to dance around the rest of his question.

Well, I think the question PFS is a clinically meaningful endpoint across multiple diseases. It really is. And lung cancer, unfortunately, has been a disease where there have not been many really remarkable advances until maybe the last 10 to 15 years. And so people have wanted to see overall survival improvement. As outcomes get better and better, it becomes more difficult to actually demonstrate overall survival. And so there may be a future where PFS could be considered in the United States as the only endpoint needed as long as you can show lack of detriment. You're not hurting people with the OS and that people are getting some benefit there. I don't know that we're there today.

And if you think about antibody drug conjugates, they are much more potent cytotoxics that are given directly to the cancer cells than IV chemotherapy, and you would expect a profound PFS benefit that, hopefully, would translate into overall survival. And so I think that there our differences and studies and endpoint somewhat based upon the timing and the initiation of the studies rather than a fundamental belief in the mechanistic action of different drugs.

And as to your second question of how excited I am or the speed at which I'm going there, we are -- we have a Phase III-ready asset. We are data-driven. We are disciplined. We have a great portfolio that can be combined with and you'll have to stay tuned.

Carter?

Carter Gould, Cantor Fitzgerald. Dr. Green, you alluded to your biomarker strategy for, I believe, for your TROP2. Can you provide any further detail there and how you're thinking about deploying that? There's additional work that needs to be done before we see that rolled out? And any details particularly around differentiating versus some of your competitor approaches with their -- there were biomarker strategies in the space.

Yes. So I'll just say something and I'll hand it to Marjorie. I think it's important that we have -- that one has a biomarker plan and a biomarker ability, but that biomarker ability can be broadly distributed, especially in the United States and Europe and other places. But the other sort of thing I just want to emphasize what Marjorie said is that just because you have a biomarker, it doesn't mean that you're going to use that biomarker in every indication. But with that, Marjorie?

Yes. No, no. Thank you. We haven't been as public about our biomarker plan as some peer companies have been in talking about what they're doing. And we have extensive IHC capabilities that through the very large development program that we've done with our partners in China, you also might have seen some of the digital pathology information that has come out at ASCO this year that we are working on. And so as Dean said, it is not a one-size-fits-all approach. And I think it underlies the mechanism of antibody direct conjugates and how you're trying to predict response because there are multiple pieces that go in. And each company's drug is different, the ADCs are different and how you might approach selections difference as the antibody against the target, how well does it internalize, what does the linker payload do? What is the expression level on different tumor cells? How effective is the bystander effect? How much efflux pump is there in a particular tumor type? All of those can change response and therefore, prediction of response may vary tremendously based upon the ADC. So I can say is that, that probably gives you -- I can't tell you because the drugs are different. The biomarkers are different. The tumors are different. The settings are different. And so it depends that we are well set up in our ongoing Phase III studies.

Courtney?

Courtney Breen. Just a question on the heme portfolio that you characterized on the slides today. This hasn't necessarily been an area that Merck has been in commercial markets with in the past. And certainly, you've done some deals recently that perhaps others had stepped away from. And so I would love to understand kind of why is now the right time for Merck to succeed in this space? And why are these assets going to set you up for success here, particularly given kind of some others have accelerated past you, thinking about Lilly with potabritinib and some of the others as well. So I would love to just hear a little bit about why you believe now is the right time for Merck?

I'll let her -- Marjorie touch on the different assets, especially the ones that you mentioned. And then I'll make some comments in relationship to our ambition to move into heme, especially after -- we felt that it was a really important place for us to make a good foray in because it's such an important part of oncology.

Yes. No, thanks for the question. Each of the assets, we think, is compelling and the -- has the ability to make a meaningful benefit for people with different hematologic diseases. And many of these diseases are ones that are often chronic in nature. And so thinking about different assets such as like [indiscernible], this is a drug because it has a slightly broader kinase activity and it also has a bit of a flexible binding that can adapt to different mutations. Preclinical studies have demonstrated that there are low rates of development of resistance in the target over time when compared to other laboratory animal model studies of other assets and what's been published, for example, in [indiscernible] 1. And so it's that kind of what can you get from that is potentially people do not develop resistance. And with the mutations of the binding site that then allows for treatment across multiple lines or the preserved ability to continue to use a drug like nertinib. And so that was what was really interesting to us about it.

I think that our studies also were done to truly because this is a disease where people have been using sometimes the same therapy since the first-generation drugs for a long, long time, and they haven't moved off of them, to really make sure that we are comparing against what is a first-line standard of care. We didn't combine multiple populations into a study and try to sort of say this works. So we really took a very different development approach to reflect the practice of physicians and the needs of the patient. So that's why we're excited about [indiscernible] and why we've developed there.

Very similar considerations have gone into the other assets. So I talked about Zolibertimab from vedotin. And Polivy is a similar drug, different target that's already approved. But we saw that in some of their initial Phase III data sets that the majority of benefit was in one subpopulation of its large B-cell lymphoma, whereas ZB works in both. So those are the kind of approaches that have led to our development and why we continue to be excited about the portfolio.

I do want to pick up on one of the things that you asked, which was from a commercial standpoint. And I think it's appropriate that Jannie make a comment because Jannie's experience and solid tumor in this, we are making a foray in heme both benign heme and heme malignancy. And I think I should turn it over to Jannie.

Yes, thank you, Dean. And I would just say, we've always had an ambition to diversify beyond KEYTRUDA, right? And we're doing that in solid tumors. We've always -- and Sophie can speak to this as well, it's been an ambition to also diversify into heme malignancies. We know it is different to solid tumors, but it is adjacent. We believe that we have significant capability that we can scale across hematology as well. And again, I think even though we had the ambition, we move with the science, we move with products that we think is going to bring meaningful value. And I think we now have 5 assets enhance that in and that can take us down that path. So I don't know if there's something that you would add.

I think I think to your point, we have now critical mass in terms of hematology to be able to build the commercial organization. We are looking at a disease over a large value pool like CLL over DLBCL, but also in an area where there has been no innovation like essential [indiscernible], and we believe that we can kind of shape the market with new and effective therapy

But also in relationship to your question, I would just emphasize, when we're talking about we're trying to give you a sense of the cadence of data readouts. I mean, I think we have listed 3 PCD dates in 2027 for heme assets and then an additional one in '29. So we're trying to lay out -- these are coming and you'll see it, and it's coming sooner than I think many people recognize.

Great. Jason?

Great. Jason Gerberry, Bank of America. So I just have a question on OptiTROP-Lung05 and I preface by saying feedback we hear from a lot of oncology KOLs is reluctance to subject patients to maybe ADC toxicities in the PDL high segment. So I'm just curious if you can speak to in OptiTROP-Lung05, any color on the management of the AEs through support of care, be it either anemia requiring transfusions or any prophylactic measures with stomatitis? And then if those measures are implemented in the counterpart TROP2 study?

Yes. Thanks for the question. Benefit and risk are always critical for the patient and the oncologist, and we agree with that. And the reason you would want to consider something beyond KEYTRUDA in this population is that while survival is good, there's still a lot of people who, unfortunately, have progression and die with high PD-L1 expression tumors. So antibody drug conjugates are still cytotoxic therapy in the current generation that are out there. And so they will have cytotoxic activity or side effects. And most of them are related to where there's expression of TROP2, so you get GI toxicities with them or it's related to some small circulation of the payload, and that's where you're getting some of the hematologic toxicities.

These are toxicities that physicians are very, very comfortable in managing. In the OptiTROP-Lung05 study, the AE rate reporting, so the way AEs are reported in China studies, is that all hematologic labs are reported as adverse events, whether a physician thinks they're clinically meaningful or not. That doesn't happen necessarily in global studies. There was no use of primary growth factor support in this study for mouth sores for stomatitis in China. They do not routinely use steroid mouthwash. They'll use baking soda mouth rinse, oral hygiene, other kind of care events, and have, in our global studies, we are very aggressive with secondary use of growth factors as well as mouth care, including oral stomatitis management because the study was started a while ago, and we've learned and have really adapted.

I think there is a question that people sometimes ask about, will AEs in a China study be the same as you would see in a global study. And you can look at there are other TROP2 ADCs, who have very similar rates of stomatitis and as well as low grade and most of them are thankfully low grade as well as Grade 3, and they're fairly consistent across most of the studies.

So it's going to be -- does this affect quality of life? Are people going to be able to take it? And I think with these kinds of adverse effects, particularly low-grade ones that, yes, hematologic ones tend to not be disruptive for the patients. And it's that benefit is the PFS and OS there for these patients, and that's what will change instead of just using KEYTRUDA as a monotherapy.

Jon Miller.

Jon Miller from Evercore ISI. I'll ask a question about something else big at this conference that we haven't talked a lot about, and that's the RAS space. Dr. Green, you mentioned, do you expect to see, for instance, lung get more and more fragmented. You specifically called out RAS is a potential population where that's going to happen. But when I look at your pipeline, I see a relatively thin list of of assets in that space compared to a large list of assets in development across the field. So what are your plans for RAS? How do you think that is going to develop in lung and beyond? And when can we hear more from you about the [indiscernible].

I'm going to take a first shot and then give it to Marjorie, but I just would just -- when one thinks about the RAS space, it may be reasonable. RAS is in so many tumors. But a simple way to think about is think about lung, pancreas and CRC. The first movers in RAS were really important in G12C. I think that some of you have asked, why are you doing a RAS program. And the concern that we had back in 2018, 2019, was whether those RAS molecules could really survive the ability to get into first-line lung. And this goes to one of the comments that Marjorie says, combinability is critical. So the quality of your molecule and the combinability, in that case with a PD-1, is critically important. So we have a study that Marjorie will talk about, which is we're hoping to lay that down in first-line lung for G12C, which will be important.

We also look at the G12C and ask ourselves, what does it teach us about other tumors? G12C is not prevalent in pancreas, but it is, in some sense, in CRC. So the ability to see, even in a small percentage, what that monotherapy looks like and how well it combines with the other medicine that's not PD-1 in that standpoint, it's cetuximab. And so that data is coming out. We believe that we have to be outside of G12C clearly, and we have an asset 4716 that is advancing with pace. We -- the way I would simply say it, it's a non-G12C broader RAS molecule. We haven't cleared what it is exactly, but that's moving at pace in clinical development as well. But I think it would be worthwhile to give an update of how you look at that data, especially the ones that we hope to advance, especially in G12C and first line in lung and in CRC.

Yes. No, thank you so much. I think Dean really highlighted what -- how we've been thinking about this, and it does fit in with our strategy is that to have the best effect, you need to be able to combine and caldorasib, and you saw the breakthrough therapy designation. I talked about it has really well-tolerated AE profile combined with pembrolizumab. And the activity is compelling. And so we have a series of Phase III studies in non-small cell lung cancer. We have one in those who have TPS scores greater than 50% [indiscernible] 004. And then we also have one with QLEX combined with KEYTRUDA QLEX where we are going head to head against the 189 regimen because we are so impressed with the tolerability combinability, the importance of hitting a driver mutation with a very potent and clean targeted therapy. We also have studies in the adjuvant setting and in unresectable non-small cell lung cancer.

And then because this is combinable and you might have seen the data in colorectal cancer, we have pretty robust monotherapy activity with our G12C inhibitor compared to some of the peer assets that have published information. And when we combine with cetuximab and chemotherapy, the responses are quite robust and durable. So we have a study ongoing in colorectal cancer.

So we have a broad development program there. And as Dean said, we have MK 4716, but we're not talking about it yet. So this is an important pathway. We want to make certain that we've got assets that meet those characteristics of being single agent active and combinable to ensure that we are improving therapeutic index and ability to benefit patients.

Mohit.

Mohit Bansal from Wells Fargo. Before I start, first of all, congratulations on the data. Since I congratulated, I can ask 2 parter probably. So the question is, so since you talked about combined ability, I think how do you think about the combined ability of the top 2 ADC and VEGF PD-1 here? And when you think about the combinations in the future, I mean, yes, you have a Phase II-ready asset in VEGF PD1, but the competition is a few years ahead. How would you think about partnering your sac-TMT with other PD-1 VEGF that are out there to get to the market sooner? Because with KEYTRUDA, you did the strategy, you played the strategy where it worked out really well for you. So I just want to understand that part.

So if I understood, the question is when you have a really important compound, are you willing to combine it with other people's compound almost agnostic, a little bit of what we did with KEYTRUDA in some sense. I would say that we're always open to that, and we're always open to that, not just in oncology, but we're open to that in non-oncology where you have really important assets, whether it's WINREVAIR or something like that. So that's something we've always considered. And that's something that, depending on the opportunity.

But having said it, I do think that -- as you specifically talk to PD-1 VEGF, we have a PD-1 VEGF that we're quite confident in, and we have a really good portfolio of ADCs and other compounds that you could combine. And one of the things is when we think about those studies, one has to think about the speed, the rigor and you have to balance off sharing it and owning 100% of that combination, but you always have to balance it. But I think your point is well taken, and it's something we think about not just for our PD-1 VEGF, it's not just what we think about our sac-TMT, but it's with any asset that we have that we think could really have broad implications. So we are open to it and people know that we're open to it. We did it for KEYTRUDA. We will do it for other compounds in our portfolio, and that answer is not just limited to oncology.

Malcolm?

Malcolm Hoffman here for Evan from BMO. TROP2 agents have been more challenged in non-small cell lung cancer. So much of ASCO because this year, it feels like a discussion on how your TROP2 can be both a leader in non-small cell and a better competitor for some emerging PD-1 VEGF agents. Can you talk about, first, why you think we are seeing such efficacy in non-small cell despite other TROP2 failures? And second, what you think we have learned from this ASCO about competitive positioning of sac-TMT versus these other PD-1 VEGF agents?

So I'm going to make a flippant comment that got picked up by some of you, is that correct, at JPMorgan where I said, not all ADCs are the same. Some can be too loose, some can be too tight and some can be just right. And with that, I'll hand it over to Marjorie.

So yes, I think when we first started working with this, I was talking to the team about Goldilocks and the 3 Bears, and depending upon where you are raised, particularly if you're our China team, they didn't know that story. And so they looked at me very strangely.

It is -- they're not the same. I think that's the hard thing is we think that the ADCs are similar and they're truly not. And so I can't speculate about data sets that you've seen, but you've seen high response rates durability in nonrandomized data sets in the first-line setting with TROP2 ADCs. And I think that there's a lot of different factors that go into successes of studies. But we're very confident in the data that you see, you can't do much better than a randomized Phase III well-conducted study, like we've seen with OptiTROP-Lung05 as well as the other data sets that they've generated. So it's a nonanswer, I think, but it goes back to Dean's part. They're not all the same.

And I would just emphasize the linker payload of Kelun, this TROP2 ADC, as you can see from the slide, is not the only asset. Similarly, I would just say the linker payload of Daiichi Sankyo that they really pioneered is also important, and we don't just have one asset. But how you position these different flavors given the molecular design differences, one has to think thoughtfully about those differences. But I don't -- I want to make sure we respect very much the linker payload of Kelan and go back to the slide. It is not just 1 compound. And we respect very much the linker payload, which is different for Daiichi Sankyo. And you see how we advance them but we're not -- we're advancing them in different ways and different tumors.

All right. Maybe just a couple of more questions. Nick.

Nick Jennings, Goldman Sachs. A question on read-throughs or learnings from OptiTROP-Lung05. First, in lung. What, if anything, in the data makes you feel more confident in the maintenance setting or adjuvant setting? And then outside of lung, are there any derisking things that you see for other indications that you're running in TroFuse? And then finally, is there anything that you can share in terms of prospects for any other interim reads for the TroFuse trials? Are there any trials progressing where you could actually see an interim?

So I'm going to turn it over to Marjorie. But as you guys know, famously, we do not comment on interim analysis. With that, Marjorie.

We don't comment on our analyses. Yes, I am sorry, I had echo Dean there. I think learnings what I was happy to see was consistency of data from sort of the Phase II data sets into the OptiTROP-Lung05, including, as you get into bigger studies will safety be the same, and we saw very consistent data. And so that's, sort of, you think about how do you take that kind of information. This is also not the first Phase III that we have from our partners. They've had multiple Phase III readouts. And so we're seeing consistent data across multiple indications with the AE profile, with the dose modification, with the discontinuation. And that is how we have learned in our global studies to be able to ensure that AE management is as tight as possible.

Physicians are so good at learning how to manage toxicities over time. But in global studies, we don't want them to have to learn in real time because it puts the patient in a bad spot and our ability to show a benefit at a disadvantage. And so that information has informed for how we are overseeing and how we're managing our Phase III programs.

Vamil?

Vamil Divan from Guggenheim. So 2 for me. So one, obviously, you laid out a lot of -- what you've done to diversify away from KEYTRUDA. Just curious if you want to comment more on kind of where you see openings to further differ supply, whether it's modalities, mechanisms based on it was at ASCO or just more generally and feel free to take that outside of oncology, if you want to.

And then just the second part is just around the -- obviously, a lot of interesting data from China. You guys are taking advantage of this. Just how were thinking of balancing, I guess, obviously a large U.S. biopharma company, how you're balancing sort of leveraging the speed of development in China, but also investing in the U.S. I think a lot of concerns raised here around what this means for the U.S. biopharma industry. So any comments you want to make there?

So I'm going to take your last question because I heard that completely. I think that China is an important player, and we've recognized that. I mean I just -- our partnership with Kelun is not just about assets, it's about their people and how they think. And we're very lucky to have that collaboration. And we have recognized that, and I can't remember when it was publicly disclosed. Maybe it was publicly disclosed in '22, something like that, but we have worked with them longer than that. And so we have enormous respect for what they do. But I also want to just emphasize that there are so many important things that are happening outside of China. And I would just emphasize, for example there is a possibility that for the first time after, I don't know, 3, 4 years, it could be "a cancer vaccine" does -- and I don't mean hepatitis B, GARDASIL or EBV, I mean that. And that's something that we're extremely lucky to be partnered with Moderna. So I just want to make sure that, that's emphasized.

And then when you look at -- you guys talked about the KRAS space. You have to give credit to, for example, Amgen and Mirati. They pioneered that with Switch2. And you have to give incredible kudos to the work done from Rev Med using a tri-complex inhibitors. So for us, it's important to take innovation from the best places throughout the globe. And I hope that we continue to do that because these diseases take more than one bright idea. So that's where I would lay that question is. What was the first?

Part one was other areas within oncology that you might consider moving into?

So one is the heme. We just want to make sure you guys realize we're making a array in heme. And I'm not sure if he's listening, but it's a little bit of a homage to Roy Baynes, who's a heme malignancy who was stuck doing a whole bunch of solid tumor stuff and did a pretty reasonable job if I may say so. But this is a bone marrow transplant heme malignancy guy. So if we're successful with this, I hope that he will eat at a burger joint with me, and I will give him enlicitide, but that's a place.

But the other place is tissue targeting. We think tissue targeting is really important. We talked about antibody drug conjugates. We talked about Kelun, we talked about Daiichi Sankyo, but we have not revealed the internal pipeline that is moving fast. Tissue targeting is not just with a chemo payload. There's other payloads that you can do. And increasingly, the work -- actually, you have to give Roger some credit at a different company who was very much advancing T-cell engagers largely in heme malignancy, but there's been a corner turn with T cell engagers in solid tumors.

So you see it in our -- right? We look at KEYNOTE-189 and Cetera, that's great. But for small cell lung cancer, what you see is that we're trying to do KEYNOTE-189 there. How we're trying to do it, we're trying to use a next-gen chemo with an ADC and the next-gen IO with a T cell engager. And if that works, we wonder how broad that principle is in places where maybe pembro didn't work as well as we had hoped. So those places are really important to us.

So I know there's still a few hands going up. We may be able to remain here for a few minutes after we're done to answer any follow-up questions, but we'll end with Meacham.

Meacham from Citi. On your broader ADC strategy, given sector MDs studied across various indications and assuming it moves into earlier lines, across different tier indications. How do you think about downstream treatment sequencing with your other ADC especially [ 41 ADC? ] Just trying to get a sense of your internal framework for avoiding ADC overlap across targets, payloads or tumor indications.

Yes. I mean I will give it to Marjorie. But every time you come up with therapy as great as KEYTRUDA. Number one is not everyone responds, right? And the other second thing is you can respond and then not respond. So it's almost like an incessant need for constant innovation. So with that, I'll turn it over to Marjorie.

Yes, I think this is why we have such an extensive biomarker program in our sac-TMT firm as well as in our other targeted therapies is that it is -- because of antibody drug conjugates as one example and here what you've asked about, have multiple ways that they can work through bystander effect through sort of the differences in the payload, the DAR, there are going to be differences amongst all of these drugs. And so some of them may need to have specific enrichment to get to where you may want to use drug A versus drug B.

Yes. I think it's to be determined how these will separate at what time. We've already seen some antibody drug conjugates approved to have biomarkers, like in ovarian cancer, wherever that has happened, and we've seen them in bladder where it doesn't. So I'm not going to speculate on the future. I think it is important to understand where people are most likely to have benefit and least likely to have detriment. And that will help separate out how these drugs work over time is the general guess.

There's very immature data about the ability to sequence antibody drug conjugates. There are some -- there are small data sets looking, for example, at the Daiichi's great DXD platform showing that there is less response. When you do, for example, in HER2-positive breast cancer, one into the next. It doesn't mean that, for example, like a [indiscernible] couldn't work, but the same payload may have some challenges. And I think that there is a lot of interest in thinking about what is the mechanism of resistance? Is it [indiscernible] kind of mutation? Is it pump? Could you change the payload to where the pump doesn't kick the payload out? And that will help with the sequencing part. This is true just like with chemotherapy itself is that we generally don't give taxane 1 straight into taxane 2 for most tumors. There are some kind of brakes in payload switching or chemotherapeutic switching. And I think the same thing will be true for ADCs. I'm speculating though.

All right. Thank you all again for your time and attention and some really great questions. We appreciate it. Dean, anything you'd want to close with?

Please enjoy. There's bacon in the back. And [indiscernible], we hope, will be available shortly...

Thank you for standing by. Welcome to the Merck & Co., Inc. Rahway, New Jersey, USA, First Quarter Sales and Earnings Conference Call. [Operator Instructions] This call is being recorded. If you have any objections, you may disconnect at this time.

I would now like to turn the call over to Mr. Peter Dannenbaum, Senior Vice President, Investor Relations. Sir, you may begin.

Thank you, Julie, and good morning, everyone. Welcome to the First Quarter 2026 Conference Call for Merck & Co, inc. Rahway, New Jersey, USA. Speaking on today's call will be Rob Davis, Chairman and Chief Executive Officer; Caroline Litchfield, Chief Financial Officer; and Dr. Dean Li, President of Research Labs.

Before we get started, I'd like to point out that we have items in our GAAP results such as acquisition-related charges, restructuring costs and certain other items that we have excluded from our non-GAAP results. There is a reconciliation in our press release.

I will also remind you that some of the statements that we make today may be considered forward-looking statements within the meaning of the safe harbor provision of the U.S. Private Securities Litigation Reform Act of 1995. Such statements are made based on the current beliefs of our company's management and are subject to significant risks and uncertainties. If our underlying assumptions prove inaccurate or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

Our SEC filings, including Item 1A in the 2025 10-K, identify certain risk factors and cautionary statements that could cause the company's actual results to differ materially from those projected in any of our forward-looking statements made this morning. Merck & Co., Inc., Rahway, New Jersey USA, undertakes no obligation to publicly update any forward-looking statements.

During today's call, a slide presentation will accompany our speakers' prepared remarks. These slides, along with the earnings release, today's prepared remarks and our SEC filings are all posted to the Investor Relations section of our company's website.

With that, I'd like to turn the call over to Rob.

Thank you, Peter. Good morning, and thank you for joining today's call. Advancing and delivering breakthrough science to address unmet medical needs remains the foundation of our strategy to create sustainable value for patients and shareholders. We continue to make tangible progress in accelerating and augmenting our pipeline. And with the recent new product launches, the transformation of our portfolio to a far more diversified set of commercial drivers is now well underway.

Turning to our first quarter results. We delivered year-over-year growth with revenue of $16.3 billion, driven by continued strength in oncology, animal health and growing contributions from new products. We remain confident in our outlook for 2026, which Caroline will speak to in a moment.

We also achieved several important pipeline milestones, the FDA approved IDVYNSO as a new treatment option for adults with virologically suppressed HIV-1, reflecting our ongoing commitment to innovation to address the evolving needs of people living with HIV.

Additionally, the FDA granted priority review for I-DXd, our antibody drug conjugate being developed in collaboration with Daiichi Sankyo for adult patients with previously treated extensive stage small cell lung cancer.

In ophthalmology, we initiated Phase IIb/III studies in neovascular age-related macular degeneration for MK-8748, our TIE-2/VEGF bispecific antibody. The second candidate from our acquisition of iBio. We also presented important Phase III results across multiple other therapeutic areas.

Finally, in our Animal Health business, we have high expectations for long-term growth, driven by new and ongoing product launches. We're pleased to have introduced NUMELVI to the U.S. market, the first and only second-generation JAK inhibitor for allergic dermatitis in dogs.

Our planned acquisition of Terns Pharmaceuticals with its promising candidate for certain patients with chronic myeloid leukemia is another example of our science-led business development strategy in action. TERN-701 has the potential to be a best-in-class therapy in a disease where there is an opportunity to further improve depth and duration of response for patients. Given the substantial unmet need for additional options, we believe TERN-701 has multibillion-dollar commercial potential and will be a significant driver of growth in the next decade. This transaction demonstrates our disciplined approach to pursuing business development when compelling science and value align. And we are confident in our belief that TERN-701 can benefit patients while generating value for our shareholders.

Looking ahead, we continue to expect a particularly robust period of Phase III data readouts from novel candidates over the next 18 months. Our portfolio is undergoing a meaningful transformation to one with a rapidly expanding and diversified set of growth drivers. We're in the midst of initial launches of over 20 new products, almost all of which have blockbuster potential across a broad set of therapeutic areas.

To move with the speed and precision this opportunity demands, we announced an evolution of our commercial operating structure. Our new business unit model, organized around products in therapeutic areas is built to drive accountability, sharpen focus and increase agility, ensuring that every part of our commercial organization delivers on the promise of our pipeline for patients.

We're pleased to welcome Brian Ford to our executive team to lead our new specialty, pharma and infectious diseases business unit. While Yani Ushausen has been appointed to lead our new global oncology and MSD International business unit. Corp Guindo has taken leadership of a newly formed strategic access policy and communications unit. Each of these individuals brings deep experience to these important roles. Together, this leadership team and structure will enable strong execution of our strategy, which includes extending our leadership in oncology while building a powerful, diversified portfolio across a range of therapeutic areas. We're confident that this change will best position us to deliver on a potential commercial opportunity of over $70 billion by the mid-2030s from these 20-plus anticipated new growth drivers alone.

We're also taking important additional steps to accelerate our ongoing transformation as it relates to artificial intelligence. Last week, we announced a multiyear partnership with Google Cloud to scale advanced AI, data and agentic capabilities across our company. This complements our recently expanded collaboration with Tempus AI designed to advance our precision oncology strategy as well as a recent agreement with the Mayo Clinic that will allow us to leverage Mayo's clinical insights and genomic data sets at scale. Together, these efforts support improved productivity across our organization and create a real opportunity to advance the innovation in our pipeline with greater speed and with a higher likelihood of ultimately reaching patients.

As we look forward, we continue to see robust demand for our innovative medicines and vaccines around the world. We're investing behind our pipeline, optimizing our operating structure and are fully committed to our purpose of using leading-edge science to save and improve lives. We're encouraged by the progress we're making and look forward to the many significant milestones coming in the months ahead.

In summary, we remain confident in our strategy and in our ability to deliver sustained growth and value for our shareholders.

Before I turn the call over to Caroline, I want to recognize Sanat Chattopadhyay and Joe Romanelli, both of whom have announced the retirements from Merck. Sanat and Joe have made lasting contributions to our company and to the patients we serve, and I want to thank them for their many years of impact. And now to Caroline.

Thank you, Rob. Good morning. As Rob noted, we delivered growth in the quarter driven by continued strength in Oncology and Animal Health as well as increasing contributions from our many compelling product launches. Our commercial and operational execution continues to enable us to generate strong results in the short term while we advance our broad and deep pipeline and invest in innovation to deliver long-term value for patients, customers and shareholders.

Now turning to our first quarter results. Total company revenues were $16.3 billion, an increase of 5% or 3% excluding the impact of foreign exchange. The following revenue comments will be on an ex exchange basis.

In Oncology, sales of the KEYTRUDA family of products which includes KEYTRUDA and KEYTRUDA QLEX, increased 8% to $8 billion, with global growth driven by continued strong demand from metastatic indications and robust uptake in earlier-stage cancers.

Strong utilization in tumors that primarily affect women, including breast and cervical cancer, continues to be a key contributor to growth. In addition, we saw increased use of KEYTRUDA in combination with Padcev in locally advanced or metastatic urothelial cancer. In the U.S. growth benefited by approximately $250 million from the timing of purchases.

We are pleased with the positive feedback following the recent launch of KEYTRUDA QLEX, Sales in the quarter were $128 million. On April the 1st, we received the permanent J code, and we look forward to having an even greater impact on patients and health care systems.

Our broader oncology portfolio achieved another quarter of strong growth. Notably, WELIREG sales increased 43% to $199 million driven by continued uptake from ongoing launches in international markets and increased use in certain patients with previously treated advanced renal cell carcinoma in the U.S. We look forward to potentially reaching more patients with renal cell carcinoma, following positive results from the LITESPARK-011 and -022 studies.

In Vaccines and Infectious Diseases, GARDASIL sales were $1.1 billion, a decrease of 22%, driven by lower demand in China and Japan, consistent with our expectations. In the U.S., sales declined 10%, primarily due to timing of CDC purchases, which was partially offset by price.

In pneumococcal, CAPVAXIVE continues to progress well, with sales of $142 million, an increase of 31%. Outside of the U.S., sales were driven by uptake from ongoing launches in certain markets. In the U.S., growth was driven by increased demand from both retail pharmacies and nonretail customers, partially offset by a reduction in wholesaler inventory.

In Cardiometabolic and Respiratory, WINREVAIR continues to have a positive impact on patients with pulmonary arterial hypertension. Global sales were $525 million, a reflection of the continued strong demand for this important therapy. In the U.S., we continued to see steady progress with more than 1,600 new patients having received a prescription and an increase in usage by patients with background therapies do not include a prostacyclin. Outside the U.S., we continue to progress with securing reimbursement and ongoing launches.

Sales of OHTUVAYRE, a novel maintenance treatment for adults with COPD, were $131 million. As expected, sales were adversely impacted by the CMS reimbursement change as well as Medicare deductible resets. We are encouraged by the prescription trends, which began to recover in March.

Consistent with our strategy to maximize OHTUVAYRE's strong potential, we are making investments to reach more patients and physicians, which we expect will accelerate growth in the second half of the year and beyond.

Our Animal Health business delivered another quarter of strong growth, with sales increasing 6%. Livestock sales grew 8%, driven primarily by higher demand for ruminants and poultry products as well as price. Companion animal sales increased 4% due to new product launches and price, partially offset by a reduction in vet visits.

I will now walk you through the remainder of our P&L, and my comments will be on a non-GAAP basis.

Gross margin was 81.9%, a decrease of 0.3 percentage points.

Operating expenses increased to $15.2 billion, including a $9 billion onetime charge related to the acquisition of Cidara Therapeutics. Excluding this charge, operating expenses grew 2%, reflecting increased investments in support of our key growth drivers, partially offset by benefits of our multiyear optimization effort and recognition of a portion of the external funding for sac-TMT.

Other expense increased to $318 million, primarily reflecting financing related to recent business development transactions.

Our tax provision was $957 million. As a result of the nontax deductible onetime charge for Cidara, we had a pretax loss this quarter resulting in a tax rate of negative 43.5%.

Taken together, we reported a loss of $1.28 per share. which includes a negative impact of $3.62 per share from the onetime charge related to Cidara.

Now turning to our 2026 non-GAAP guidance. We have narrowed the range and raised the midpoint of both our full year revenue and EPS guidance. We now expect revenue to be between $65.8 billion and $67 billion, representing growth of 1% to 3%, including a positive impact from foreign exchange of approximately 1 percentage point using mid-April rates.

Our gross margin assumption remains approximately 82%.

Operating expenses are assumed to be between $36 billion and $36.8 billion. This range does not include the proposed acquisition of Terns or any additional significant potential business development transactions.

Other expense is expected to be approximately $1.3 billion.

We assume a full year tax rate between 23.5% and 24.5%, which reflects the nontax deductible onetime charge for Cidara.

We assume approximately 2.48 billion shares outstanding.

Taken together, we expect EPS of $5.04 to $5.16, including a positive impact from foreign exchange of approximately $0.10 using mid-April rates.

It is important to note that this guidance does not include the impact of the proposed acquisition of Terns, which is expected to close soon. We expect the transaction will result in a onetime charge that will increase research and development expense by approximately $5.8 billion or approximately $2.35 per share.

In addition, ongoing investment to advance TERN-701 and the assumed cost of financing will negatively impact EPS by approximately $0.12 this year.

As you consider your models, there are a few items to keep in mind. For KEYTRUDA, recall that while growth benefited from the timing of wholesaler purchases in the first quarter, we will face a corresponding headwind in the third quarter.

For ENFLONSIA, consistent with the first quarter, we expect minimal sales in the second quarter, given the seasonal nature of the product and continued high levels of RSV monoclonal antibody inventory in the market. We are actively engaging customers in advance of the RSV season and remain focused on educating health care professionals and parents on the importance of protecting infants from this potentially serious disease and expect shipments to increase in the second half of the year.

Lastly, we expect SG&A expenses to increase over the remainder of the year as we invest to maximize the impact of our recent and upcoming launches.

Now turning to capital allocation, where our strategy remains unchanged. We will prioritize investments in our business to drive near- and long-term growth, including new product launches and a robust pipeline.

We remain committed to the dividend with the goal of increasing it over time.

Business development remains a high priority as evidenced by our recently announced acquisition of Terns. We maintain the ability within a strong investment-grade credit rating to pursue additional, science-driven, value-enhancing transactions going forward.

We are on pace for approximately $3 billion of share repurchases this year, as previously communicated.

To conclude, we are confident in the outlook for our business driven by global demand for our innovative medicines and vaccines, including our many new product launches. We remain committed to bringing forward medically significant innovations that will enable us to deliver value to patients, customers and shareholders well into the future.

With that, I'd now like to turn the call over to Dean.

Thank you, Caroline. Good morning. Progress continued with a steady cadence of clinical and regulatory development. Today, I will provide updates in cardiometabolic and respiratory, oncology, infectious diseases and ophthalmology then conclude with key upcoming milestones.

Starting with cardiometabolic and respiratory. The global burden of atherosclerotic cardiovascular disease remains significant. And with recently updated clinical guidelines recommending lower LDL-cholesterol thresholds, there remains a need for innovation that is broadly accessible.

At the American College of Cardiology Congress last month, additional Phase III data were presented for enlicitide, our investigational oral PCSK9 inhibitor. Enlicitide is designed to reduce LDL cholesterol in a similar manner to PCSK9 antibody therapies with the simplicity of a daily pill.

The Phase III CORALreefAddOn study demonstrated statistically significant and clinically meaningful greater reductions in LDL-cholesterol at 8 weeks compared to other oral add-on lipid-lowering therapies when added to background statin therapy. Of note, enlicitide also showed statistically significant greater reductions across key secondary endpoints, including apolipoprotein B and non-high-density lipoprotein cholesterol.

The CORALreef program has generated compelling evidence for the efficacy and safety of enlicitide As a pill, enlicitide has the potential to democratize access to a potent lipid-lowering therapy. With clinical guidelines targeting lower LDL-cholesterol targets, the field of preventive cardiology is increasingly energized and focused on early, aggressive LDL-cholesterol reduction.

Also at ACC, we showed full results from the Phase II CADENCE trial, evaluating WINREVAIR in adults with combined post- and pre-capillary pulmonary hypertension and heart failure with preserved ejection fraction. WINREVAIR met the primary endpoint of reduction from baseline in pulmonary vascular resistance compared to placebo. At the 0.3 milligram per kilogram dose, WINREVAIR prolonged the time to first occurrence of a clinical worsening event, which was an exploratory secondary endpoint with a hazard ratio of 0.18. Results provide compelling proof-of-concept and warrant further evaluation in Phase III. This is an underdiagnosed condition with an extremely poor prognosis. There are currently no approved therapies.

Moving to Oncology, KEYTRUDA now has 44 FDA-approved indications across 19 tumor types as well as 2 tumor-agnostic approvals and continues to generate evidence further transforming cancer care.

In the first quarter, the FDA and European Commission approved KEYTRUDA in combination with paclitaxel, with or without bevacizumab, for the treatment of certain patients with platinum-resistant ovarian cancer based on the findings of KEYNOTE-B96. This is the first PD-1 inhibitor based regimen to show a statistically significant improvement in both progression-free survival and overall survival versus paclitaxel with or without bevacizumab for these patients.

We also announced findings from the KEYNOTE-B15 study demonstrated KEYTRUDA plus Padcev reduced the risk of event-free survival related events by 47% and risk of death by 35% for cisplatin eligible patients with muscle invasive bladder cancer. This is the first and only perioperative immunotherapy plus ADC regimen to extend survival for these patients. Based on these data, the FDA has accepted supplemental BLA filings for KEYTRUDA and KEYTRUDA QLEX under priority review and is targeting an action date of August 17. KEYNOTE-B15 is the sixth study of a KEYTRUDA-based regimen to demonstrate overall survival in an earlier stage cancer and, if approved, would mark the 12th earlier-stage indication for KEYTRUDA.

We also continue to make progress across the broader oncology portfolio. WELIREG, our first-in-class oral HIF-2-alpha inhibitor initially approved for the treatment of certain patients with von Hippel-Lindau syndrome has now shown additional clinical data for patients with renal cell carcinoma across multiple stages of disease.

The LITESPARK-022 study evaluating WELIREG plus KEYTRUDA in the adjuvant setting, demonstrated a 28% reduction in the risk of disease recurrence or death compared to KEYTRUDA alone. In addition, the LITESPARK-011 study, evaluating WELIREG plus Lenvima, demonstrated a 30% reduction in the risk of disease progression or death in certain patients with advanced RCC and versus cabozantinib.

Supplemental applications for WELIREG in combination with KEYTRUDA or KEYTRUDA QLEX based on LITESPARK-022 were granted priority review by the FDA with the PDUFA date of June 19. The FDA also set a PDUFA date of October 4 for WELIREG in combination with Lenvima based on the LITESPARK-011 study.

As announced last week with our partner, Eisai, the combination regimens from the LITESPARK-012 study did not meet the dual primary end point of progression-free survival and overall survival for the first-line treatment of patients with RCC and compared to KEYTRUDA plus Lenvima. The data from the study provides learnings to the broader program. Studies from the LITESPARK clinical program, including LITESPARK-033 and 034, evaluating WELIREG in combination with zanzalintinib, are ongoing.

Together with our partner, Daiichi Sankyo, we announced that the biologic license application for ifinatamab, deruxtecan, or I-DXd, for the treatment of extensive-stage small cell lung cancer in certain patients with disease progression has been granted priority review by the FDA. This was based on results from the Phase 2 IDeate-Lung01 trial, and the Phase 1/2 IDeate-PanTumor01 trial. The FDA has set a PDUFA date of October 10.

As Rob mentioned, we continue to identify external opportunities to strengthen and diversify our pipeline, most recently with the proposed acquisition of Terns Pharmaceutical. TERN-701, a novel oral allosteric inhibitor of the BCR::ABL oncogene is being evaluated for the treatment of certain patients with chronic myeloid leukemia and has the potential to be an important addition to our growing hematology pipeline. Clinical data has shown encouraging activity with promising rates of major molecular response and deep molecular response by week 24.

Importantly, this includes responses in patients with high disease burden, who previously received multiple lines of therapy. We are eager to get to work with the talented Terns team to advance this program in a timely fashion.

Turning to HIV. Last week, the FDA approved IDVYNSO, our once-daily, single-tablet 2-drug regimen of doravirine and islatravir, a next-generation nucleoside reverse transcriptase inhibitor that blocks translocation, indicated for the treatment of certain adults whose HIV-1 is virologically suppressed based on 2 Phase III SWITCH study. Approval was previously granted in Japan.

IDVYNSO is the first approved 2-drug regimen that does not include an integrase strand transfer inhibitor.

At CROI, additional data was presented demonstrating noninferiority and a similar safety profile at week 48 versus the 3 drug, INSTI-based regimen, Biktarvy, in adults who had not previously received antiretroviral treatment. In addition, IDVYNSO was shown to maintain virologic suppression at week 96 in adults who switched some other oral antiretroviral therapies, including Biktarvy.

Islatravir, a potent long-acting antiviral that forms an anchor for additional regimen is currently being evaluated in late-phase trials as a once-weekly combination with Gilead s lenacapavir, an HIV capsid inhibitor, and separately in combination with ulonivirine, an internally developed non-nucleoside reverse transcriptase inhibitor. We plan to present data from our HIV pipeline at an upcoming medical meeting.

Next to RSV. In February, positive new data were presented for ENFLONSIA for the prevention of RSV lower respiratory tract disease in infants and children under 2 years of age at increased risk for severe disease over 2 seasons from the Phase III SMART study. These findings will be shared with global regulatory authorities with the intent to obtain an expanded indication.

RSV is a leading cause of infant hospitalization globally and is especially serious for children under 2 years of age at high risk for severe disease. These data provide additional evidence for ENFLONSIA for the prevention of RSV in younger children who remain at risk entering their second season.

Earlier this month, the European Commission approved ENFLONSIA for the prevention of RSV lower respiratory tract disease in newborns and infants during their first season, based on the Phase IIb/III CLEVER and Phase III SMART trial.

Next, in ophthalmology. We remain focused on retinal diseases associated with vascular leakage and neovascularization, with emphasis on improving structural and functional outcomes for patients and helping reduce the burden of certain retinal diseases. This month, we initiated 2 pivotal Phase IIb/III trials evaluating MK-8748, an investigational bispecific Tie-2 agonist/VEGF inhibitor for the treatment of neovascular age-related macular degeneration. The MALBEC and TORRONTES studies are the first trials in a broader late-phase development program for MK-8748. The decision to advance development is based on promising results from the Phase I/IIa RIOJA trial.

In closing, we anticipate multiple events and milestones across therapeutic areas in the coming months, including, in oncology, please mark your calendars for our annual investor event at the ASCO Annual Meeting in Chicago on the evening of Monday, June 1, where we will outline progress on our oncology pipeline and strategy. On the regulatory front, as noted, potential approvals for KEYTRUDA plus Padcev in MIBC, WELIREG in expanded RCC settings and for I-DXd in extensive stage small cell lung cancer.

In HIV, data from the Phase III ISLEND-1 and 2 trials evaluating islatravir and lenacapavir, a once-weekly oral 2-drug treatment regimen in collaboration with Gilead.

In cardiometabolic and respiratory, the September 21 PDUFA date for WINREVAIR for the label update based on the Phase III HYPERION study and the Commissioner's National priority Voucher Process for enlicitide is progressing.

In immunology, data for tulisokibart, our TL1A inhibitor, based on the Phase III ATLAS-UC trial in ulcerative colitis and Phase II ATHENA study in SSc-ILD.

Finally, in ophthalmology data from the Phase III BRUNELLO study of MK-3000, our novel Wnt agonist, being evaluated in patients with diabetic macular edema and the Phase II portion of the RIOJA study of MK-8748 being evaluated for the treatment of patients with certain retinal diseases.

I look forward to providing further updates throughout the year. And now I will turn the call back to Peter.

Thanks, Dean. Julie, we're ready to start the Q&A now. We'd appreciate if analysts would limit themselves to a single question today so we can conclude the call at the top of the hour. Thank you.

[Operator Instructions] Our first question comes from Carter Gould with Cantor.

Maybe we'll start on the pipeline on MK-3000. How are you thinking ultimately about dosing the 1-year BRUNELLO data is likely not going to inform much on duration interval and the Lucentis comparison is going to leave lots of questions unresolved. I fully appreciate that 40% have suboptimal responses to VEGF, but can this reach your targets if it ultimately requires every 4-week dosing? Or put differently, are there reasons you have conviction about every week or every 12-week dosing?

Thank you very much. So just stepping back, MK-3000 is our potential first-in-class novel candidate targeting Wnt pathway. -- for retinal vascular disease. Almost all the other mechanisms are based on VEGF. And as you've highlighted, up to 40% have suboptimal response to VEGF.

In terms of dosing, frequency, when one sort of does these trials once start at every 24 weeks and upon doing that, then you go further from that. So we believe that one should focus on Q4 weeks, but one should not only focus on Q4 weeks. So your question, which I think alludes to, are we considering other frequencies, the answer is absolutely yes. But the initial focus is on 4 weeks because that is very important to get into the label.

I just want to also highlight really quickly that it's not just MK-3000, it's MK-8748, which is the novel bispecific directly agonizing Tie-2 that we're also excited about, and that as well is advancing in Phase IIb/III trials in retinal vascular disease.

Our next question comes from Jason Gerberry with Bank of America.

Had an update or a question on the WELIREG clinical update on LITESPARK-012 recently provided. And I wanted to get your sense, does this provide any concerning read-through to some of the ongoing readouts for LITESPARK-022 and the ability to see OS benefit there? And also, you have another frontline study with WELIREG, albeit in a post-PD-1 setting. So just kind of curious if you can speak to some of the read-throughs to some of the ongoing trials.

We were having a hard time hearing you, Jason. Let me restate the question. And then I think I'll get it. I think what you're asking, given the LITESPARK-12 outcome, how does that make us think about getting OS in some of the upcoming LITESPARK studies and what's our overall view as it relates to WELIREG. I think that's the way I was trying to ask.

Thanks because I could not hear quite well. In relationship to the other ones like LITESPARK-022, LITESPARK-011, which have PDUFA date in June and October. I think we're very bullish in relationship to how those will turn out. And also in relationship to the question that you have of how -- what's the readout of this trial that had 3 agents involved, which is a PD-1, VEGF TKI and a HIF-2-alpha, I think we are studying that data, but I would be very cautious to sit there and say that has any negative implication to other trials where, for example, we have a VEGF TKI and WELIREG or a PD-1 and WELIREG.

Our next question comes from Michael Yee with UBS Securities.

As we think about coming up to ASCO, where you will obviously have your SAC PMT featured in lung cancer, of course, obviously, PD-1 VEGF also featured in a plenary as well from a competitor, how are you thinking about the dynamic of a sac-TMT in the context of PD-1 VEGFs and your own Lenova asset and perhaps accelerating that? And maybe just give us a snapshot being as to where we stand on these 2 types of programs.

Yes. So I'll answer the question too individually, but I will also answer what I think you're alluding to is the possibility of combinations of that. So in relationship to the PD-1 VEGF, we're very interested in the space. We shared some encouraging early data at AACR. And our construct of the leading PD-1 VEGF is most similar to ours. And so we're looking at our own data. But to be frank, we're also looking at the broader field as well. And so we're eager to move PD-1 VEGF Ford in our trials.

And one of the issues that we think in our hands, a PD-1 VEGF, if it should be better than KEYTRUDA, we have a plethora of agents that would benefit from a combination with either KEYTRUDA or a KEYTRUDA plus or a PD-1 VEGF. So we're advancing that.

In relationship to sac-TMT, I believe that at the ASCO, our strong partner and collaborator Kelen will provide optotroplung-05 in first-line non-small cell lung cancer. And I think people will look at that data very carefully because it may reflect on our global trials, which are not just within China but throughout the globe.

In relationship to the question that you said is, is there any possibility of thinking about combining those to -- the answer is absolutely yes. And we're developing the information and also taking a scan to the outside world as to where and when to best combine a PD-1 VEGF with the rest of our portfolio.

Our next question comes from Asad Haier with Goldman Sachs.

Congrats on all the progress. Maybe just a high-level one back to BD, you've been fairly active across a number of different areas, and you're saying you're ready to pursue additional transactions. So just level set us on where you still see the biggest gaps in your portfolio that could benefit from more BD as you scan the therapeutic landscape? What's the sweet spot now in terms of deal size? And is there a point at which the BD lever starts to diminish in importance just given your growing confidence in the growth trajectory out of the mid part of the next decade with the portfolio transformation that's already underway?

Yes. Asad, I appreciate the question. I would just start by saying we are very confident in the assets we have, the new assets we bought in through business development as well as the continuing progress we're making with our pipeline. So that continues and that grows. That said, we also continue to focus on business development. And as we've said in the past, we don't necessarily target specific therapeutic areas as the first question we ask. We always ask the first question, which is where do we see a significant unmet scientific opportunity where the science is compelling and can address.

And in doing that, that allows us to think about where to focus. So we start with the science. We then asked the question, how does it fit strategically and then move to the value question and where we see science and value in line we move. So that has not changed. Our approach remains to be that as our focus.

From a size perspective, we continue to look anywhere in the $1 billion to $15 billion range with that kind of being the sweet spot. But as we've consistently said, we have the capacity to go beyond that for the right strategic deal. And we will, if and when we see that. So that is where we're looking as far as the therapeutic areas where we do continue to see interesting science, obviously, oncology continues to be an area where there's a lot going on. We continue to look.

Immunology is an area where we continue to see interesting opportunities as well as cardiometabolic is probably the 3 most likely areas, but we are willing to be opportunistic beyond that as well.

And I guess, Peter, did remind me one part. When will we have less urgency to do a deal. My view is we can always do better. We can always grow stronger. And if we have the capacity, we will continue to invest. As Dean has said, we think in terms of one pipeline, whether it's internal or external. And so that mix of internal plus external will be an ongoing part of our strategy, you will not see that change.

Our next question comes from Vamil Divan with Guggenheim Securities.

I just had going back to Win Revere. I appreciate your comments about the cadence data in ACC. Just curious if you could provide any updated thoughts on how the discussions with the FDA are going on moving forward the Phase II program there, you remain confident on the clinical listening being can be the primary endpoint of the Phase III? And then just maybe any sort of rough estimate on how long you think you would actually take to execute a Phase III program in this indication.

Yes. Thank you very much. So in relationship to Wind River, I mean it's reshaping the standard of care in PAH. And now the question is whether or not we can move it to a different segment of pulmonary hypertension, those people with heart disease. The patient population that we pick is a relatively small patient population of those patients who have pulmonary hypertension and heart disease. But it's probably one of the biggest unmet needs that I know of in this patient population, who at least the way that I would describe it is a very different patient population than that of PAH. And one could actually say is more complicated, is older and has more comorbidity.

We think that the cadence gives that proof of concept -- as I had said previously, it's fine to talk about the primary end point reductions in PVR. But at least for me, in this patient population, it will be very important to have the endpoints that allow someone and when I mean someone, I mean patients, providers and payers to really see a compelling conglomerate of endpoints in the time to clinical worsening. And -- and that's where we will be having our discussions with the FDA.

I think the other one that will be important is defining the inclusion criteria in relationship with the FDA and also the broader community in relationship to how do you actually operationalize the clinical trial, but also for everyone to be very clear that in our minds, this is a patient population that is an orphan patient population.

Our next question comes from Daina Graybosch with Leerink.

Yes. I want to go back to ASCO and the data we're going to see from Kalon on OptiTROP-Breast05. That's a China study. And I wonder what should we keep in mind as we look at those outcomes on how it could or could not translate globally any differences in what you're doing globally? Or any other things to keep in mind.

Yes. Thank you very much for that question. So just stepping up at a higher level, we think sac-TMT, it is a coke to ADC, but we think that it has some important differentiation. And we believe that the sac-TMT has a potential to be I think Elliot has often said a cornerstone and Margaria said a workhorse ADC. And we have 17 Phase III studies, 13 are in first movers. We have an in blast, non-small cell lung cancer, gyn, gastric and bladder.

When we do our trials and when we speak to our close partner, Kalon, we use the fact that they are, in some sense, doing signal finding in registrational trials in China. And we recognize China is different, but these are important data for us.

In relationship to the exact details of the sac-TMT and the Kian, I would just remind you that the OptiTROP-Breast05, they will have data. But I think it's very important to sit there and go, if -- how one thinks through that in terms of how that would read out. We are following their data very much. But I think that we are guided we are guided by the results. I do want to emphasize that in their OptiTROP, it's sac-TMT plus KEYTRUDA versus KEYTRUDA in PD-L1 positive first-line non-small cell lung cancer. And it's very important that if one wants to do an ADC plus KEYTRUDA versus KEYTRUDA in the United States, ex China, one has to look at where a PD-1 and what's the range with which the PD-L1 cut-off is.

And so for us, this is the first Phase III combination study of sac-TMT and KEYTRUDA to read out. We have 50% of our Trou studies are evaluating KEYTRUDA combos in our TrophUse-007, our global study at ACTMTand KEYTRUDA versus KEYTRUDA in TPS greater than 50% in first-line non-small cell lung cancer. And I emphasize that simply because in the United States and ex China, TPS greater than 50% is where KEYTRUDA has an indication.

Our next question comes from Steve Scala with TD Cowen.

What are the gating factors for FDA acceptance of the enlicotide application? And Dean, can you speak to the changes that you're pursuing on titration? What shorter durations are you pursuing? And is the 15 minutes you spoke to previously before or after administration of the drug?

Yes. So I would just say that the enlicitide, as we've said out is we want to have the first and best-in-class potent oral PCSK9. It's designed in a very similar manner to antibody. And the data from the Phase III as a as we have discussed, I think lay out the value statement and relationship to its potency in terms of all the important by proteins. In relationship to the CNPV, the issue in relationship with the CNP is just for all of us to understand that the NPD process is a little bit different, which is we -- it's almost like a rolling submission, sort of way to think about it.

And through that rolling ambition, at the end of that sort of rolling submission, that's when the FDA sits there and gives you a letter and a PDUFA date. And so we are actively in those discussions with the FDA. And then as we normally do when we get formal acceptance of the complete file, which is a little bit different in the CMPB we'll make an announcement. I will emphasize that in our discussion with the FDA, -- what is very important to them is us really showing them that the CMPD program is important that we're addressing an important U.S. public health crisis that we're delivering innovative cures and we're increasing domestic drug manufacturer and supply chain resilient. So those are all important to the FDA, and we are in really good conversations with them.

And so I think that is going quite well, and it's progressing well. I would imagine that our estimation that we could get an approval at the second half of this year I see no reason to doubt that at this moment in time. In relationship to what you said in relationship to this issue of how you would take it -- we're also in the discussion with the FDA as to what the exact label is in relationship to how they will talk about prescriptions and when to take it and how to take it. And I don't want to get ahead of that conversation because those are extremely active conversations as we speak.

Our next question comes from Chris Schott with JPMorgan.

I just wanted to touch base on TL1A I think this one's got maybe a little bit less attention than some of your other late-stage readouts this year. But can you just talk a little bit about the role you're seeing TL1A playing in the IBD space? And maybe more broadly, when we think about immunology and IBD, there does seem to be more discussions about combination therapy as maybe the next step for the market. I'm just interested in Merck's approach here kind of building on the TL1A as I think about a broader pipeline?

Yes. So I would begin to say that throughout the immunology sort of field, there are certain nodes that are really important 23 is an important note. TNF is an important note. And that's how the field is set up. We wonder whether TL1A is such a node and that -- and our hope is to laSocobar could be 1 of the first and best-in-class TO1As. So that's in that sort of framework.

The other thing that you've just said, I think is really important is that there is increasing interest in combining different these nodes. This is something that was tried 10, 15, 20 years ago, and it didn't turn out well. But now the data suggests that in certain cases, you could begin to combine. When you look at the AE profile of tubasocopart, it's if you take the Phase II data, not just our Phase II data, but across the Phase II data. It is a member of the TNF superfamily, but from an AE profile, I might describe it as a kinder gentler AE profile than other NOTO-TNFs and with profound efficacy.

So I think combinations will be employing. -- in relationship to what we hope to see in relationship to Phase III ulcerative colitis and chronic and Crohn's disease, we have readouts coming out we hope to be first mover, but I also want to emphasize that we also think that TL1A may be also distinguished not just to be an important note, but it may be important for not just inflammation or dampening but also for fibrosis. And we have Phase II data in SSC ILD and in HS that's coming in 2026. And that hopefully will define the unique role or the unique position that T1 has with all the other major notes.

Our next question comes from Louise Chen with Scotiabank.

I wanted to ask you about the CADENCE study. There was some debate on the results that you recently presented at a medical meeting. And I'm wondering what you think the Street may be missing about the competitiveness of your product.

So I'm not sure I know everything that you're referencing. In terms of the competitiveness of our product, I don't know how else to answer it is, I don't know from a competitive standpoint that there's any treatment for this patient population. And when I look out, I'm not so sure that I see something that, that will break that barrier. In terms of whether or not you can make a Phase III, but sort of models what happens in the Phase II. I think that's where the focus is.

And that's been the focus in our conversations with KOLs, but also the FDA. And there is a clear understanding that this patient population, this patient population is 1 with a tremendous unmet need. And so I don't know that I would call it competitive sort of dynamic sort of thing. It's whether someone for the first time can have a compelling treatment for a patient population that is in dire need.

Our next question comes from Omar Raffat with Evercore.

I wanted to touch up on some incremental information that came out on your turns deal, which I don't think we discussed on the call you as did earlier. And by my math, it looks like the incremental patients may have had an MMR achievement rate of something like 2 out of 10 or something along those lines. Could you just speak to the -- that drop and how does that change or not change your overall thoughts about the drug's profile? Because presumably, that's like the real target population early in the launch?

Yes. Thank you so much for that. So I would just say that in this -- in CML, there's multiple approved therapies, and it appears that there is significant unmet need. And the value proposition for us for turns to 101 is whether or not it has the potential to be a best-in-class Alister TKI with high selectivity and improved therapeutic index. When data is presented at some of these meetings initially when they're early, Oftentimes, they're stated in 1 way. But for us, it's really important to always look at that data, whether it's especially when you go to ASCO, AACR or ASH, we look at it immediately in the eyes of how do you think in terms of registration.

And it's very important to translate whatever the abstract says to, what I would say, a more conservative ITT population consistent with regulatory standards. Given that, what was laid out at these public congresses is turn stated to 75% MMR and 36% DMR achievement rate. As the data evolved and we were looking at very specific patient-level data we believe that the MMR will be north of 50%. And within the confidence interval as had been publicly stated. And we think that in MMR in that sort of range is extremely compelling.

And then the other point that I would just highlight is we also think that the DMR rate is also very interesting to look at and whether or not this drug could not only create a best-in-class in relationship to MMR, but whether it could catalyze the field to increasingly think of DMR as a treatment goal.

Our next question comes from James Shin with Deutsche Bank.

Dean, have a question. Can you help us distinguish MK-6837 from sac-TMT? And then just going back to the TL1A question, is there a view within Merck that TL1A could stand alone in immunology because from a market or commercial perspective, immunogy seems to be very much a portfolio-driven strategy. Some of your peers have large portfolios, and there's a very competitive remote that's built with that?

Okay. So let me ask -- let me tackle the immunology question really clearly. We're very focused on TL1A, but if you ask me is TL1A is our ambition to stop at TL1A, -- would we use TL1A as a beach at to expand and extend. The answer is we would undoubtedly move it to expand and to extend -- we had expanded from IBD to other conditions, and we would advance it to conditions where the combination of immunofibrosis would be really important.

In relationship to other molecules, of course, if one had a leading TL1A that could advance through the series of different indications that we have, then in each 1 of those indications, you would immediately think of what's the combinatorial partner whether it be in IBD or HS or in SSC IOD. So we would immediately think about doing that as well. So we are focused on TL1A, but that focus does not create a situation where we're not thinking about not just whether we can be first and best, but what's next as well. And I think the other question was related to MK-6837. Is that correct?

I didn't catch the other one. MK-6837 is another ADC, which had a unique payload, and we have discontinued that especially when you see the profound impact of sac-TMT and also in relationship to -- we've always said that we're very interested in the ADC field in changing the target but also changing the payload and thinking about combinatory or cycling different payloads as the field moves on in the antibody drug conjugate.

Maybe I could just add 1 little bit as a teaser, maybe to what you'll see as we go into next year and beyond. In our invisible pipeline we often refer to we have other assets in the immunology space that you're not seeing right now. So just to reinforce Dean's point, we aren't just a TL1A company. We have other things in development beyond that. And as we move forward in time, you'll start to get a better sense of that as we unleash that as it moves into Phase I.

All right. Thanks, James. We'll squeeze one last question in before we end the call.

Our last question comes from Geoff Meacham with Citibank.

All right. Dean, in HIV, just given the recent approval of Avito, can you talk about how you guys see the competitive setup and related, I know you have prep coming up, but how much of a strategic priority is HIV and infectious disease when thinking about the overall BD strategy.

So in terms of our interest in HIV, there is a profound interest in really in our HIV program. And for those of you who've talked to Eliot Bar, the Chief Medical Officer, I think you can feel that just in his presence. Islatravir is a next-generation nucleoside reverse transcriptase inhibitor. It blocks translocation, and we have the daily program -- and increasingly, there is interest in going from a 3-drug daily program to a 2 drug.

And of the 2 drug daily programs, I think we're the only ones without an entity backbone. So I think that's very important. -- critically also important is that we believe ezlotivir can anchor to weekly, and you see it in later lenacapavir, which is a 2-drug combo, which hopefully will be the first Q week and then loci with UL, which is in development, and there will be data being presented, I think, in due course, it could be the smallest pill could be favorable DDI profile and be extremely effective.

And then as you said, to me, the monthly, if you could have 12 pills and protect people with MK 852 I think that would just be such an important contribution as a commercial product, but also as a global product for public health throughout the world. So if the question is, are we committed? And are we passionate about our HIV program? I hope that you heard from the tenor of my response, the answer is unequivocally yes.

Great. Thanks, Geoff, and thanks, everybody. Apologies for going over a few minutes. Give us a call if you have any follow-up questions. Thank you.

Thank you for your participation. Participants, you may disconnect at this time.

Thank you for standing by. Welcome to the Merck & Company Inc. Rahway New Jersey USA Investor Event announcing the acquisition of Terns Pharmaceuticals.

[Operator Instructions]

This call is being recorded. If you have any objections, you may disconnect at this time. I would now like to turn the call over to Mr. Peter Dannenbaum, Senior Vice President, Investor Relations. Sir, you may begin.

Thank you, Amanda. Good morning, everyone. Welcome to Merck's investor call highlighting the announced acquisition of Terns Pharmaceuticals. Before we get started, I'd like to remind you that some of the statements that we make today may be considered forward-looking statements. Such statements are made based on the current beliefs of our company's management and are subject to significant risks and uncertainties. If our underlying assumptions prove inaccurate or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

Our SEC filings, including Item 1A in the 2025 10-K as well as Tern's SEC filings identify certain risk factors and cautionary statements that could cause ours or Tern's actual results to differ materially from those projected in any of our forward-looking statements made this morning. Merck & Company Inc., Rahway, New Jersey USA. undertakes no obligation to publicly update any forward-looking statements. During today's call, a slide presentation will accompany our speakers' prepared remarks. These slides and our SEC filings are posted to the Investor Relations section of our company's website.

Our speakers this morning include Rob Davis, Merck's Chairman and Chief Executive Officer; Dr. Dean Li, President of Merck Research Laboratories, Jannie Oosthuizen, Executive Vice President and President, Oncology and MSD International; and Caroline Litchfield, Chief Financial Officer.

With that, I will turn the call over to Rob.

Great. Thanks, Peter. Good morning, everyone. The ongoing successful execution of our science-led strategy is enabling us to positively impact patients and drive sustainable growth over the long term. We are transforming our company with launches underway for more than 20 anticipated new growth drivers, almost all of which have blockbuster potential and together represent a combined non-risk-adjusted potential commercial opportunity of over $70 billion by the mid-2030s. Innovation-driven value-enhancing business development is an important element of our strategy to expand and diversify our pipeline across a broad set of therapeutic areas, including oncology.

Today, we're excited to announce our proposed acquisition of Terns Pharmaceuticals. Its lead candidate, TERN-701, is a potent, orally available next-generation allosteric tyrosine kinase inhibitor being studied in certain patients with chronic myeloid leukemia or CML. We believe TERN-701 has the potential to be a best-in-class therapy, driven by high selectivity and an improved therapeutic index that could lead to efficacy advantages versus currently approved TKI agents. Patients with CML often remain on therapy for many years. And while significant advances have been made, there remains opportunity to further improve disease control and treatment outcomes.

In addition, challenges with today's treatments related to durability and tolerability lead to frequent switching. TERN-701 is designed to address these unmet needs and provide an important potential new option for patients. Given the size of the addressable population and the remaining unmet medical need, we believe TERN-701 has multibillion-dollar commercial potential and will be a significant driver of growth in the next decade.

This acquisition builds upon our deep expertise in oncology and strengthens and complements our growing hematology pipeline, which has significant future commercial potential as part of the oncology business unit under Jannie's leadership. More broadly, this transaction reflects our commitment to acting decisively when compelling science and value align and our confidence in the benefits TERN-701 will bring to patients while generating value for our shareholders over time. We're eager to welcome the talented Terns team to Merck and look forward to the contributions they will make as part of our organization.

With that, I'll turn the call over to Dean.

Thank you, Rob. Good morning, everyone. Our company has made remarkable progress in treating cancer, most notably solid tumors, but there is more work to be done. As we have advanced our oncology strategy and diversified our clinical pipeline, hematology has become a particular area of opportunity and interest. The acquisition of Terns provides our company with an opportunity to further investigate the potential of TERN-701 for certain patients with CML. CML is a slow-growing cancer derived from the bone marrow's blood forming stem cells and is characterized by a distinct translocation between chromosomes 9 and 22 known as the Philadelphia chromosome.

Historically, due to limited treatment options, the diagnosis of CML was almost universally fatal. The advent of tyrosine kinase inhibitors fundamentally transformed the treatment landscape and significantly improved outcomes for patients. Today, CML is generally managed as a chronic condition with many patients remaining on therapy for extended periods of time, often for many years. However, long-term exposure to existing therapies is associated with increased risk of relapse due to the emergence of resistant driver mutations, primarily in the kinase domain or active site of the [ BCR::ABL ] protein.

Similarly, while adverse events tend to appear in the first few months, the cumulative risk of developing intolerance to one or more TKI therapies increases with the duration of treatment and the number of lines of therapy. As many as 40% of patients treated with active site TKIs switch therapies within 5 years. In the second line and later settings, the majority of people with CML do not achieve a deep molecular response. So despite multiple available treatments, there remains significant need for further options.

The focus of development has therefore evolved with enhanced emphasis on increasing the depth of response and overall disease control while improving long-term efficacy, safety, tolerability and overall quality of life. TERN-701 is a potent, selective, oral next-generation allosteric BCR::ABL tyrosine kinase inhibitor. Unlike traditional active site competitive TKIs, TERN-701 is designed to specifically target a distinct site on the ABL protein that controls kinase activity, thereby overcoming mutations that occur in the kinase active site.

This differentiated mechanism is designed to inhibit the oncogenic driver while minimizing off-target effects. The high degree of target selectivity observed with TERN-701 supports the potential for higher dosing with more complete inhibition and an improved therapeutic index. TERN-701 has demonstrated preclinical activity against multiple resistance mutations, further supporting its continued evaluation across different lines of therapy.

In the ongoing Phase I/II CARDINAL study, TERN-701 has demonstrated promising activity in patients with Philadelphia chromosome-positive CML previously treated with at least 1 TKI with encouraging rates of major molecular responses and deep molecular responses observed by week 24, key measures of the reduction of BCR::ABL cancer cells. Importantly, these responses were achieved in a previously treated patient population with high disease burden, including those previously treated with multiple TKIs and even those who had previously relapsed while receiving Asciminib, the only allosteric TKI approved for treatment of CML.

We reviewed the totality of data for TERN-701 and estimate that the final MMR achievement using a more conservative intent-to-treat population would be approximately double the MMR and double to triple the DMR achievement of approved TKIs, including Asciminib. Based on this analysis, TERN-701 has the potential to be a best-in-class therapy for certain patients with CML. Furthermore, TERN-701 has also shown a faster kinetic response to achieving MMR and DMR than approved treatments, providing additional support for its potential best-in-class profile.

Safety is a critical consideration in CML given the long-term nature of treatment. To date, no dose-limiting toxicities have been observed for TERN-701 and the majority of treatment-emergent adverse events reported have been low grade. Furthermore, the overall safety and tolerability profile appears favorable with a low incidence of serious adverse events based on data available to date. Dose expansion is ongoing to further characterize the safety profile and inform optimal Phase III dose selection.

Looking ahead, we see an opportunity to apply our global clinical development capabilities to evaluate the potential of TERN-701. We intend to design a rigorous and appropriately powered clinical program that addresses both frontline and later-line treatment settings in CML. As with all of our programs, our focus will be on generating high-quality data that clearly characterizes TERN-701's benefit risk profile and supports its potential role in the treatment landscape. TERN-701 further augments and complements our growing and innovative hematology pipeline, spanning multiple modalities and disease areas.

In addition to our existing approval for KEYTRUDA, we have a series of pivotal readouts from a pipeline of innovative hematology candidates within the next couple of years, including Nemtabrutinib, our non-covalent BTK inhibitor, Bomedemstat, our LSD1 inhibitor and Zilovertamab vedotin, our ROR1 targeting ADC. As well as MK-1045, our CD19xCD3 T-cell engager, which is being evaluated in a Phase I/II study.

We believe TERN-701 provides a strong strategic fit within our broader hematology ambitions and reinforces our commitment to science-driven innovation with the goal of making a meaningful difference for patients over the long term. Finally, I'd like to reiterate Rob's comments and convey my admiration and respect to the Terns team for their remarkable achievements in discovering TERN-701 and advancing the science in this important disease area.

With that, I will turn the call over to Jannie.

Thank you, Dean. As both Rob and Dean highlighted, we are committed to advancing the science in hematology and an area of significant clinical need and opportunity to positively impact patients. Given our expanding pipeline, we are well positioned to launch several innovative therapies in the coming years. And so I am excited to add TERN-701 to our portfolio, and I'm confident in its potential to deliver meaningful benefit for patients. CML is a chronic disease that often requires long term and in many cases, lifelong treatment. As outcomes have improved, patients are living longer, which has contributed to the increasing prevalence of the disease over time.

Across the U.S., key European markets and Japan, there are estimated to be 18,000 new patients diagnosed with CML each year. As the treated population grows, factors such as tolerability and adherence have become increasingly important. Despite multiple approved treatment options, unmet need remains, particularly in the context of long-term duration. TERN-701 has the potential to be the best-in-class treatment for certain patients with CML. And as Dean noted, it will be complementary to our current hematology portfolio where we expect a cadence of launches over the next several years.

Given the substantial unmet need for additional options for certain patients with CML and the significant potential benefits of TERN-701, we believe it has multibillion-dollar revenue potential and can be a meaningful driver of growth beginning in the early 2030s and continuing through the next decade.

With that, I will turn the call over to Caroline.

Thank you, Jannie. Turning to the financial details of the transaction. We are confident that TERN-701 can be a meaningful driver of growth in the next decade, and this transaction has the potential to create significant value for shareholders. Merck has agreed to acquire all outstanding shares of Terns Pharmaceuticals for $53 per share, representing a total equity value of approximately $6.7 billion or approximately $5.7 billion net of acquired cash, cash equivalents and marketable securities.

We intend to finance the transaction primarily through new debt, and we do not expect an impact to our credit rating. The transaction is expected to close in the second quarter of 2026, subject to the tender of a majority of Tern's outstanding shares as well as regulatory approvals. We expect the transaction to be accounted for as an asset acquisition.

As a result, we expect a charge to research and development expense in 2026 of approximately $5.8 billion or approximately $2.35 per share. In addition, we expect a negative impact to EPS of approximately $0.17 in the first 12 months, which represents investment to advance the development of TERN-701 and the assumed cost of financing. The impact of these charges will be reflected in both our GAAP and non-GAAP results. Our balanced approach to capital allocation remains unchanged. Business development continues to be an important priority. We remain committed to a strong investment-grade credit rating while preserving capacity within it to pursue additional value-enhancing transactions.

In summary, the success we are having in advancing and augmenting our pipeline, including through science-led business development, such as the planned acquisition of Tern, increases our confidence in our ability to deliver important innovation to patients and sustain our long-term growth while providing value to shareholders. I will now turn the call back to Peter.

Thank you, Caroline. Amanda, we're now ready to begin Q&A. I just want to let everyone know that in the room with us is Dr. Marjorie Green, Senior Vice President and Head of Oncology Global Clinical Development.

[Operator Instructions]

Our first question comes from Evan Seigerman with BMO Capital Markets.

Congrats on the deal. I really want to kind of get into the nitty gritty. In your diligence, can you explain why TERN-701's allosteric inhibition may be more optimal than other active site TKIs in CML.

So this is Dean. I'll just make some really quick comments, and I'll hand it back to Marjorie. So you're asking whether or not inhibitors of an allosteric why they are potentially superior than those who are orthosteric, which is the active site. I think the data from Asciminib suggests that there are advantages of an allosteric site over an active site or an orthosteric tyrosine kinase. That sort of had been played out. In relationship to turns, we believe that this allosteric inhibitor could even have more superior efficacy in relationship to the TKIs at our active site and also potentially in a basket in relationship to those who are also on allosteric. But Marjorie, is there anything you wanted to add?

Yes. No, thanks, Dean. Part of the interest, I think, has to do with mechanisms of resistance that occur over time. And it does appear that for the different classes of TKIs, there are different mechanisms of resistance. And it is potentially possible that by using different allosteric, you're able to overcome resistance that could exist with some of the first and second-generation TKIs.

Our next question comes from Alex Hammond with Wolfe Research.

On safety, Turns noted that there was no symptomatic lipase elevation. Should we interpret this as there were asymptomatic elevation? And if so, is there any concern in larger clinical trials that you could see symptomatic elevations? And I guess as a follow-up, what's your appetite for continued BD and any additional therapeutic areas of interest?

So why don't -- I'll have Marjorie take the first question, and then I'll answer the second question about continued interest in business development.

Yes. Thanks for the question. Regarding the lipase elevations, Terns has publicly disclosed and data that we have confirmed that rates of lipase elevation are present, but they are low grade and in their nature, the majority of adverse effects that occur with these kind of PKIs, you will see signals within the first 6 months of exposure for majority of AEs. And so I think, again, what they are showing are consistent with the class low-grade lipase elevations.

Thank you, Marjorie. And then as it relates to business development, to be clear, hopefully, what you see here is a transaction that very much fits into what has been our ongoing business development strategy, which, as you know, and we've communicated pretty consistently always starts with the question, do we see a significant unmet need where there is innovative science that can address it? And then we ask, how does it fit within the strategic portfolio that we have?

And then finally, do we see an opportunity for compelling value creation. And in this case, we hit all of those factors. As we look forward, our interest continues to be to add more to the portfolio while we are very excited about what we have, and I give all the credit in the world to Dean and our scientific team for what we've been able already to achieve as represented in the potential $70 billion plus. And remember, that's only from a select set of assets, not from our entire portfolio. We feel very good about where we are, but I always believe you can do more.

And in that spirit, we will in a disciplined way, continue to look for opportunities. I'm excited that we can add to our position in oncology here, both in terms of putting ourselves in a position to continue to be a leader in oncology, but also to diversify within the oncology space and add to our hematology portfolio. Beyond that, we continue to be interested in other therapeutic areas. and it should not be a surprise. Immunology continues to be an area we often look and are excited about cardiometabolic vaccines, ophthalmology based on some of the recent deals we've done. And then we're always opportunistic, again, starting always with the first question, where is the science pointing us and what do we see as the need? And that is always the driver.

Our next question comes from James Shin with Deutsche Bank.

First question is for either Dean or Marjorie. Appreciate 701's frontline CML trial as against investigator's choice for MMR. Any chance this frontline trial includes testing for noninferiority and possibly superiority to Asciminib? And one for Rob and team. It seems you have line of sight to late line and frontline CML for 701. So how much does this terms deal change the $70 billion peak pipeline figure presented earlier this year?

So this is Dean. One of the things I just want to be a little bit cautious about talking about a potential Phase III development program is Number one, we don't have ownership of this company or the control of the study design. And our intention always is to pursue a robust and appropriately powered program that demonstrates the unambigorous promotable advantage of whatever medicine or vaccines we're advancing. But I would just ask Marjorie is there anything else that you want to add?

No, I agree. We're very excited about the potential of TERN-701 to make a clinically meaningful difference for people with CML, and we will execute a robust, well-developed program should the transaction go through.

And as it relates to the $70 billion plus, you should assume, as we said, with multibillion-dollar plus opportunity, commercial opportunity from this asset, we are growing it. I'll let you determine how much multibillion is.

Our next question comes from Louise Chen with Scotiabank.

Congratulations on the deal. So I wanted to ask you if you could elucidate a little bit more how TERN-701 would fit into the treatment paradigm if it's approved? And then how do you expect it to take share? Would it be new patients or from existing therapies?

So I'll just give a highlight, which is what we've said in the prepared remarks is our calculation based on early data suggests that there's a possibility that this drug, TERN-701 may have around 2x MMR versus approved TKIs and 2 to 3x DMR in approved TKIs and a faster kinetic response than that was treated before and also a very favorable safety and tolerability so that someone could stay on it. So I just think that, that's the scope of how we view the positioning of this scientifically, but I'll hand it over to Jannie for a commercial view of that potential ambition.

Yes. So thank you, Dean. So as we said, we see this to be a multibillion-dollar commercial opportunity. I'm not going to so much talk about the assumption on share. I think the first order of business would be to stand up the development program to really generate the data that is needed to define the differentiation that we're going to have against other options, both from a clinical option point of view, depth of response, durability and tolerability. And we will share more as the Phase III program shapes up, but we think that this could be a meaningful choice in the CML setting.

I might just add, I think the other part of the question, primarily, we see this as new patients coming on therapy and being able to move into that space. That's the way we valued it. Obviously, over time, we will look to see for the opportunities for switch as well. But given the number of new patients that unfortunately continue to become inflicted with CML every year, there's a meaningful opportunity there. Having them stay on therapy chronically allows you to effectively multiply that over time. And then to the extent we drive switch over time, it even goes higher. So all of that is why we're so confident in the multibillion-dollar opportunity.

Our next question comes from Jason Gerberry with Bank of America.

Maybe just a follow-up question just on the commercial point. I guess from your standpoint, which of the, I guess, data variables in future data really is key to having success driving a switch in a market like this? Is it really the safety? Is it the lack of food effect or efficacy differentiation in the head-to-head comparisons? And then just as a follow-up, did you guys describe any value to assets beyond 701 in this deal?

Yes. So let me just take a first stab at things. In relationship to the basic question, at least my simple sort of view is especially in oncology, especially oncology, but in all therapeutic areas. efficacy and showing improved efficacy is a critical component of how we look at our own internal programs and how we look at every other program when we do business development. So it's a common sort of thing. Efficacy is critically important. But with that, I'll hand it over to Jannie.

Yes, absolutely. I will tell you what makes us excited as a commercial organization is if you can have a treatment with double the MMR, 2 to 3x DMR and that faster kinetic response to achieve both MMR and DMR on top of a very tolerable product, I think this will be a significant choice in that first-line setting. So again, as Rob said, there's about 80,000 patients annually across the U.S., Japan and key European markets that is newly diagnosed with CML -- so we see a product with a profile like that capturing a significant number of patients in that first-line setting and could motivate some physicians to switch other patients on to a therapy like this.

And Jason, in terms of the valuation, our valuation is based on TERN-701.

Our next question comes from Michael Yee with UBS.

This is [ Dina ] on for Mike. Thinking about time lines for the pivotal study, I know that Terns had previously said that the second-line study would start first and then the first line or frontline study would be running in parallel, but about 6 to 12 months behind. Is there any way that, that time line can be accelerated, especially for the front line? And how are you thinking about just the path forward from there?

So I'll just take it really quickly. I want to be a little bit thoughtful and careful as to how to answer any questions directly related to clinical trial design and time lines until we are fully in control of Terns. And also, this will also require discussions clearly, whether it's Terns or us with the regulatory agencies. So I don't want to get ahead of that. But there is nothing that Terns has said that we would sit there and we are going with the assumptions of what they have said publicly.

Our next question comes from Geoff Meacham with Citi.

This is Mary Kate on for Geoff. So Terns has mentioned additional data from the CARDINAL trial is to be expected in the second half of this year. I guess just should we expect a similar readout in terms of time lines? And could you maybe walk us through how you're looking at the ongoing clinical trial and what you'd like to see to further bolster your confidence in this program?

I mean I would just emphasize the way that we look at this program is we conduct a comprehensive and rigorous evaluation of all available data. And at that level, we're looking at patient level data and always thinking consistent with regulatory standards for registration. So we're comfortable as we get more data and as people -- more people are treated with this drug and also those who are treated with the drug get more experience, that will inform how we think about future development and the time lines related to that. But Marjorie, is there anything else that you would like to add?

Yes. No, thanks. Terns has done a fantastic job with their development of 701. And I think they've talked about publicly and shown that they've already completed dose escalation are in randomized dose finding. And so we would work with ensuring that, that data is well described and understood and presented in a timely fashion.

Our next question comes from Daina Graybosch with Leerink Partners.

Rob, you talked about the 4 pillars of Merck's BD strategy and one is an opportunity for compelling value creation. And I wonder if you could talk more specifically in this case, why Merck owning this asset is going to create more value for your shareholders.

Well, obviously, one of the strengths we've had over the last several years is the position we've been able to enjoy in oncology. And we've been working hard to expand that. As Dean highlighted, we have multiple assets that we'll be launching in the hematology space over the coming years. This adds to that. We've already been building the commercial capabilities and leveraging, frankly, what we already know from the solid tumor side to leverage over to that. And given the scale we have, both from our clinical programs, which I continue to be proud of what we've done. I think we have the best clinical team in the industry in oncology.

And so the confidence that when we give them an asset that they can bring it through and deliver it clinically, we've shown we can do that consistently. And so that gives me great confidence in our ability to drive this program to success. And then given the scale we have commercially in the marketplace, we will leverage that full network to drive this product. So this is something that builds on where we want to be. As Dean has always said, we started, we were a leader in IO. We are committed to being a leader across broader oncology with a very diversified portfolio of assets, and this adds nicely to that. So I'm very confident in the compelling value this is going to bring for shareholders.

Our next question comes from Mohit Bansal with Wells Fargo Securities.

This is Will Zhang on for Mohit Bansal. Congrats on the deal. So I guess moving over to the first-line setting. So [ Gleevec ] and its generics still have meaningful share in the first line despite [ Scemblix ] being approved and available there. How are you thinking about overcoming this first-mover advantage with TERN-701? And just where do you see opportunity for TERN-701 to take share here?

Yes. So I'll let Jannie talk about the shares and the commercial aspect, but I think it will be important to hear from Marjorie as the person who leads late-stage oncology, why she and her teams are excited about bringing this opportunity to patients with CML.

Yes. Thanks, Dean. There -- you're correct. There are still physicians who are using the first-generation Gleevec. They've gotten used to the management of the side effects and have seen consistent efficacy over a long period of time. However, there remains significant unmet need in CML. And I think that's what drives a change in therapy showing that value. If you look at some of the data sets that people still present, you'll see a reference to MR2, which is what Gleevec was [ pounded ] for was the ability to get a cytogenetic negative test result with the drug.

However, what's becoming more and more apparent is that while the risk of accelerated phase of CML and blast phase has gone down significantly with drugs, it still exists. And so time to getting to that molecular response and depth of molecular response are important prognostic factors and prediction of how people with CML will do for the long term. So having a drug that is tolerable that people who are on for a long period of time can get an individual CML to a very rapid and deep response is very prognostic for their long-term outcomes. And we think that is what will drive the clinical uptake. There is a move to considering for some people treatment-free intervals.

And to do that, you need to have very, very prolonged deep molecular responses and people wait for several years before they even consider that. And so I think that's the value proposition that people see. It's that depth of response and the tolerability that will change therapy.

Yes, I fully agree, it's Jannie. I think as we've seen again and again in oncology, it's the data that really makes the difference. And if we can deliver that improved MMR, but as Marjorie said, the deep molecular response at 2 to 3x plus the tolerability versus current options, we are confident that we will take significant share.

Our next question comes from Umer Raffat with Evercore ISI.

I have 2 here, if I may. First of all, congrats to you guys on the deal. Two, if I may. First, just the fact that we're going into a [indiscernible] binding pocket. I guess my first question would be, have we seen any MMRs in T359 patients because I feel like there's been no conversation on that so far. Secondly, on MMR itself, I feel like any headline number is just -- there's just a lot more to it than the headline itself. So my question instead is there's a 64% MMR in 28 patients. Separately, we know 18 patients at baseline were enrolled because they discontinued because of lack of tolerability. So how much of this 28-patient denominator is driven by lack of tolerability patients rather than lack of efficacy or truly resistant patients?

So I'll turn it over to Marjorie, but I just sort of really want to emphasize that there's probably like maybe 20% to 30% of patients that demonstrate resistance and 70% of those estimated to develop a point mutation in the ABL gene. In relationship to the data that we've had, we've seen patient level data and also remember that there is continuing to be a dose escalation in relationship to the doses with which the patients are being exposed. But I was just going to turn it over to Marjorie, if there's any other considerations that she wanted to bring.

Yes. No, thanks. The Terns are doing a great job at analyzing and evaluating the potential for people with and without different kind of mutations of BCR::ABL. That data has not been publicly presented to my knowledge. And -- but these people are being enrolled into the study to understand the characteristics of TERN-701 further. I think in their public presentation that they did in December, they go through the details of how they calculated the different levels of response.

And so what we did, as Dean said, is we had patient-level data -- and we looked at it through multiple different lenses because the nature of Phase I/II studies is that you get a very heterogeneous population. And so we were able to look at people based upon prior therapies. And as Dean said, a significant number of people enrolled in these studies that had prior assay and lack of efficacy was present in a high number of them rather than intolerance. And so there's a lot of very rich data there. I can't share the full details of the work that we've done, but the study has been open for a long time, and the data that was presented at ASH had a data cut of September. And so what we were able to do is confirm this profound efficacy you hear us all talking about and that it's held up over time.

Our next question comes from Luisa Hector with Berenberg.

Just in terms of the deal valuation, so Caroline said based on TERN-701, could you add any color on how you may have changed your thought process? Is this largely based on U.S. value? Any thoughts around [ MFN ], [ IRA ], channel mix? And then just any comments on IP, just your levels of confidence in the IP.

Thank you, Luisa. So the valuation that we do considers a whole number of scenarios. What I would say is TERN-701 is a really impactful product. It's a product that has orphan drug designation. As such, as a product given the current rules, we would expect to not be included in IRA nor in MFN. Our valuation, however, is predominantly driven by the United States. So we are very confident in the valuation that we have given for the product and very excited for its launch. As we look at IP, we expect that IP will go out into the 2040s.

Our last question will come from Emily Field with Barclays.

I guess sort of a follow-up question to the earlier one on Gleevec, but asking a different way. I was just thinking back to ASCO a couple of years ago when Novartis presented the ASC4 first data. Most of the questions from the analysts then were really about the genericization of the earlier generation TKIs and how they expected commercial development from a payer and reimbursement perspective. So I was just wondering how you guys have thought about that and how the sort of generic and payer landscape may have evolved by the time this product could launch and how you'd be able to get coverage.

I'll just say from a scientific standpoint, then I'll hand it over to Jannie. My understanding from the physicians that we've talked to is that the desire or the attractiveness of that first allosteric TKI is such that people do want to prescribe it because of what they are perceived as improved ability to get MMR. And so I just want to sort of emphasize that what we believe is really important in this field is the improved MMR that we may achieve with TERN-701, but also the very much improved deep molecular response that when we look at it, we have not seen data that's similar to that outside of TERN-701. But with that, I'll turn it over to Jannie.

Yes. I mean, as we looked at it, we couldn't see any utilization management in terms of current treatment options. So we do believe that Asciminib will continue to take share. As we look at TERN-701, we do believe that differentiated data will continue to give the ability to use, and we will have time to really establish this as a treatment choice. So we do not foresee in terms of how the market currently operate that utilization management, genericization of any of these first or second-generation TKIs will affect the utilization, reimbursement and access to TERN-701, for instance.

Great. Thanks, Emily, and thanks, everyone, for your time and attention this morning. Please reach out to the Investor Relations team if you have any follow-up questions. Have a great day.

Thank you. That concludes today's conference. Thank you for participating. You may disconnect at this time.

[Audio Gap]

46th Annual Healthcare Conference. We are absolutely delighted to have Merck senior leadership here with us today. Representing the company, Caroline Litchfield, who is Executive Vice President and Chief Financial Officer; and Dr. Dean Li, who is President of Merck Research Labs, lots to talk about, both in the pipeline as well as the current operations. But to set the stage, Caroline, I'll turn it to you.

Thank you, Steve. So good afternoon, all. Thank you for being here, and thank you for your support and interest in Merck. Our company is transforming its portfolio. We're launching many new products including WINREVAIR, OHTUVAYRE, CAPVAXIVE Enflonsia and QLEX. We're in the midst of having more than 20 new growth drivers in our Human Health business. Every one of these products has the promise of advancing patient care and almost every product has blockbuster potential. And we've highlighted that there's more than $70 billion of commercial opportunity from those 20-plus products.

And it's not just human health. Our Animal Health business is also launching many products, and we expect to more than double the revenues of our Animal Health business by the mid-2030s.

And so we're increasingly confident in our future. And that future also includes a robust early-stage pipeline that will continue to evolve and hopefully yield Phase II, Phase III programs in the coming months and years that will equally drive revenues and patient impact in the 2030s.

So we're confident as a team that we can navigate the KEYTRUDA loss of exclusivity. And we talk about it as being more of a hill than a cliff as we expect our revenues to have a shallow dip before quickly turning to strong growth within a few years. And we will continue as a team to execute: execute on our launches, execute on our pipeline and continuing to augment this pipeline with scientifically focused value-creating business development so we can drive impact for patients and long-term growth for our company. So with that, we look forward to talking about anything and everything that's going on at Merck.

Great. So let's start with the pipeline. So Dean, you have 6 late-stage pipeline readouts in '26 and '27 and I'd like to ask you to rank them by clinical risk and let me just go through them for the sake of the audience, islatravir lenacapavir, MK-3000, tulisokibart, sac-TMT, the Cidara antibody and I-DXd.

So I'm going to list them by what they mean to us as a pipeline. And so I would sit there and say sac-TMT and I-Dxd are very important. They are all based on really important in most cases, Phase II. But actually, in the case of sac-TMT, they're often based on Phase IIIs from China. So that is our pivot of KEYTRUDA and chemo going to next-gen chemo.

In terms of new molecular mechanisms of actions, I think the MK-3000, the first new MOA for diabetic macular edema and neovascular AMD and clearly to the tulisokibart, where there is a possibility that this TL1A node could potentially become equivalent to the node of TNF and IL-23.

In relationship to sort of infectious disease, we're launching islatravir/doravirine, but the first time that someone could achieve a [ q weekly ] treatment is a islatravir and lenacapavir. And I think that will increased -- we already have a lot of confidence in this pathway with islatravir/doravirine so is islatravir and lenacapavir. And clearly, MK-1406 in relationship to, in some sense, a pre-exposure prophylaxis for influenza. So I think all of them are important in different ways. And so that's how I would sort of lay out the importance and relationship to our pipeline.

Okay. Great. I should have mentioned at the outset, should anyone have a question anywhere along the line, please raise your hand, and we will call on you. Lots to dig in on those products alone. But maybe we could start with MK-3000, a very exciting drug. What is the ideal target patient population for this asset? And what do you strive for in a clinical profile?

Yes. So if one looks at diabetic macular edema and neovascular AMD, that field has been transformed over the last two decades by anti-vascular endothelial growth factor molecules. And they've all come in maybe 6 to 10 years after each other. So you have Lucentis, you have Eylea, then you have Vabysmo. In every one of those situations, each one of them kind of took over the lead of the other ones using a non-inferior clinical trial. But all of them were based on vascular endothelial growth factor. This mechanism of MK-3000 is a totally different mechanism. It's based on Wnt agonism and so our hope is that we would do a clinical trial similar to the other ones that have been done. But the critical point for us is it will be important for anyone with diabetic macular edema or anyone with neovascular AMD, but critically important is around -- up to 40% of individuals don't respond to anti-VEGF or anti-vascular endothelial growth factor. So we believe that, that will be really important because it will be the first brand-new mechanism in decades for those diseases. And so that could be really exciting for the field.

And are the patients enrolled in the BRUNELLO trial, are these patients who failed VEGF?

No. So we're going to treat the trial no differently in relationship to all of the other trials, which is you basically take all comers. But essentially, you already know in those all comers, maybe 30% to 40% of the patients won't respond to anti-VEGF. So we will not be limited to those people who didn't respond. But in some sense, we will be enriched by the people who don't respond to anti-VEGF.

I see. Very exciting asset. Also on the list is islatravir. And we're intrigued by this ISLEND-1 and 2 trials. And curious, I guess, a risk with this modality could be that patients may forget a dose. So how is the trial designed? Is it patients who -- or do you exclude patients who have had trouble in trials with FAS or in the before, are you -- how are you gauging adherence? And how are you enriching the trial to assure regulators that there will not be a dosing issue with this molecule?

Yes. So these are people living with HIV. And the patients that we're doing are not patients who have virologic failures. So there's no enrichment. So this is going to be no different than any other sort of HIV study. What you've seen in our Phase II that this involves two important mechanisms, the nucleoside analog with translocation as well as the HIV capsid of our partner, Gilead. And in that trial, what you saw is you saw greater than 90% adherence and greater than 90% efficacy and we will count clearly adherence through pill count, but we believe that this once-weekly option, which will be the only once-weekly oral option for treatment will be something very important for certain patients living with HIV.

Okay. Maybe moving to another asset on the list, that being sac-TMT. What would be -- you point to as the strongest evidence that sac-TMT is better than the currently approved Trop ADCs, Trop-2 ADCs in lung and breast cancer?

Yes. So first of all, we have a Trop-2 ADC that is different. We would look at the other ADCs, one could potentially say that in one of them, the linker is a little bit loose. So you see this hematologic sort of adverse effect. The other one is quite tight. So you see the adverse effect of interstitial lung disease. So we think this is a differentiated molecules. Not all ADCs are the same. And HER2 is not the same thing as Kadcyla. And we are advancing sac-TMT in a whole series of trials, 17 trials. I think 13 of them are first movers, 4 of them are differentiated. And so we're moving in endometrial gastric, if positive, we can be the first mover of Trop-2. You specifically asked me about lung and breast. I can tell you all the theoretical, but we have a great partner in Kelun, and they have already shown Phase III trials in China that suggest that in non-small cell lung cancer in those patients with PD-L1 greater than 1, that, that would be a really important molecule. They've also done it in EGFR mutant. Again, that data is out there. And then the third place is HR positive, HER2 negative. And in each case of that, we have taken that lead and that information and formulated global trials that fit in the global setting based on those studies. And the data for those, I think many people have said they've been compelling in their differentiation in lung and in breast.

If sac-TMT does turn out to be differentiated relative to other Trop-2 ADCs, do you think the linker might be the key reason from an MOA perspective? Or are there other elements of the molecule that are...

I would say, generally, the antibody is basically saying the payload is slightly different but I do think it's all 3 combinations of the antibody, the linker and the payload. So I would say from a molecular standpoint, it could be more related to the linker. But I also think the concept that we were driving this in so many indications and tissue types that the other didn't even go into. So then you're not differentiated. You're just going there because you think your molecule has the tolerability and the durability to stay in for those cancers.

Questions from the audience? Moving to the Cidara assets. So can you just give us an update on the ANCHOR trial and your level of confidence that you are still on track to read out the trial in mid-2026?

So that trial did recruit extremely well in the Northern Hemisphere. We are definitely going to the Southern Hemisphere. We -- and I should just recount what this is, this is essentially an antiviral conjugated to a biologic backbone such that it has a long half-life and the concept is this would be a way to really reduce the chances of giving influenza, especially for those patients who are immunosuppressed, who have substantial comorbidities. We want to make sure that we are recruiting in the Southern Hemisphere because we think that it's very important to have a strain agnostic preventative in that patient population.

And I'll remind everyone that the flu vaccine does around 20% to 40% in us. But in patients who are immunosuppressed, it doesn't do that great. And in that patient population, the chances of something bad happening or a bad outcome is high. So we think this is a really important medicine for the world, but I would also just state that I'm going to imagine that the rate of vaccination in this country for flu will not necessarily increase over the next 3 to 4 years. So I think this molecule could be really important.

But Caroline, did you want to touch any of that?

So we're very excited about the promise that MK-1406 has. To Dean's point, we think this can be really impactful for people who have immunocompromised conditions or people over the age of 65. As we sized this opportunity, there's about 110 million people here in the United States. 85 million immunocompromised or with other comorbidities, a further 25 million who are over the age of 65. So what we're trying to do in our clinical program is really have a data set that will help see the impact that this protection could provide in helping stop getting the flu. And so we're progressing with our study. We have expanded and in the process of expanding in the Southern Hemisphere and would expect to read out during the early part of 2027.

Okay. A few products that aren't on that initial list though, which we discussed earlier, but are still very important, of course, first, the oral PCSK9. We had a cardiology panel yesterday here at the conference. Part of it was on lipids and the doctor believes that oral therapies are going to catalyze this market like we haven't seen in a long time. And the Merck product was front and center, albeit there was good attention on your competitor as well. But in addition to having the oral therapy, guideline changes were very much a part of the doctor's view what's going to catalyze growth in those markets. So how are you viewing that? And do you also think it's a catalyst? And also, can you include in the answer why you feel you can win in this market against what should be a pretty tough competitor?

So I would just say that I think many people don't realize that in 2013, in the American Heart Association, ACC guidelines, they took out any goal for LDL in 2013. I mean -- and in other places like Europe, they kept it. And that, I think, has done a disservice to the field and so over a decade, there hasn't been LDL levels. I believe that the American Heart Association and ACC will change that. They will drive that guidelines after more than a decade, they'll have some level for LDL, but I also think, increasingly, they look at other fields such as ASCO or oncology. I bet you they're going to not just lay a guideline but they're going to update their guidelines more effectively and more frequently.

The reason why that became so important is that a competitor or a colleague or however you want to put it, Amgen with Repatha show the VESALIUS trial. And essentially, if you had an LDL of 90 to 100, that's oftentimes your doctor says, "Well, that's kind of okay." If they could drive the LDL to 45, they got a 25% cardiovascular outcome benefit. So I think the HA and ACC realize there's a lot of movement in that space. And I think that if you get the guidelines, then you can get quality metrics than the hospitals care because if you're a hospital administrator, you don't care if it ain't in the guidelines. And I think it will catalyze the field.

In relationship to our molecule, essentially, I talked about VESALIUS. In some sense, what we try to do, and I should just highlight Repatha, which is the basis of VESALIUS was an Amgen product that Roger Perlmutter developed. We essentially had in our mind that we were going to make a biologic, a Repatha in a pill. So our molecule does exactly the interaction biochemically is exactly like Repatha. And the reason I say it is that the data that we've shown suggests that, but that makes it the most potent LDL cholesterol-lowering medicine that has ever been provided once it gets accepted. I believe that with the guidelines potentially coming in at 70 with some patient populations with 55 and increasingly drive it. A [ statin ] alone will not do it, you will need a [ statin ] and the next most important low LDL cholesterol-lowering molecule that you possibly can get. And that's what we hope to provide to patients and to people throughout the United States and the world.

And so what we have with enlicitide is very strong compelling clinical data. The United States have given us a commissioner national priority voucher. So we will be imminently filing enlicitide and an ordinary time line would take us to a Q1 '27 launch. We're hopeful, subject to that review process that we'll be launching in the nearer term.

Of course, approvals tend to reflect clinical trial design. And I imagine when this trial was designed 5, 6, 7, 8 years ago, the food dynamic was embedded in the trial design for whatever reason. But roll forward this number of years, it could be that maybe the fasting requirement is excessive, maybe it doesn't have to be that much. Is Merck doing any work to look at exactly in the contemporary world, how long that food effect has to be? Could it be shortened? Are you doing work to shorten it?

So I would answer it two ways. The answer is yes. But I would just recount that I understand that you're referring to someone else's where I don't have their Phase III, but their Phase II clearly is less LDL-cholesterol lowering. So if you take ours properly and you take theirs properly, ours is substantially more reduction in LDL. I don't know where their number is going to end up, but I suspect that even if you had a full English breakfast with ours than ours -- I still think it will be hard for people to be above ours. So ours, if you take it, you took it, you went to bed, you woke up, you took your medicine, you could have water, tea, coffee or like this for 30 minutes. If you do this, you'll get the most potent LDL-cholesterol-lowering medicine. If you sneak in a piece of bacon or something like this or a donut in there, I still think that you will have effective LDL-cholesterol but you won't have it at the level of the most potent LDL cholesterol lowering.

The question actually wasn't intended to infuse a competitor into -- it's more that your product could be -- it's a great product now, it could be even better if food restriction wasn't quite what it was. So is Merck doing studies to say, it doesn't have to be 8 hours, it could be one?

15 minutes? Is it 20 minutes? Those sort of things. Yes.

So you're doing that?

Yes. But I think the critical thing is we know that even if you did eat, where you would end up.

And knowing that this medicine, you will get up in the morning, you will take it with the other pills that you take. You can drink water, tea, coffee, you shouldn't eat for 30 minutes and in our clinical program, 96%, 97% of the patients on the program were compliant without us having to tell them what to do, they were naturally compliant with doing so.

Okay. Questions from the audience? You probably don't get a lot of BTK questions, but nemtabrutinib is a product that Merck seems to be maybe chatting about a little more about. Why is this an exciting molecule in a very competitive market?

It is a competitive market. I mean so this is CLL and -- there was a great drug that started the whole thing with Ibrutinib. But those are covalent inhibitors. And now the question is whether non-covalence can come in and go into first line. So we're really eager to see that but it's also we're talking about it not just because we're talking about nemtabrutinib. We talked about diversifying oncology. We had KEYTRUDA and they were going to diversify, and we're going to use what we knew about KEYTRUDA to get into the ADCs that we've just talked about to get into precision targeted, such as WELIREG and KRAS. But the other sort of thing is KEYTRUDA didn't have that big impact in heme malignancy. And so we have a series of compounds. It's nemtabrutinib. It's also [indiscernible] ADC. It's also our T cell engager, MK-1045 and then in the nonheme malignancies space, we have bomedemstat. So we're talking about nemta, but we're talking about 4 programs that will have readout in the next 1, 2, 3 years that is 4 products in the heme space.

Okay. One more product or a pipeline-related question then we'll get some to some business questions. But V940, will we get to Phase III cutaneous squamous cell carcinoma data this year? And if so, what should be our expectation?

Yes. So just to remind, this is the collaboration of the individualized neoantigen therapy or some people say the cancer vaccine for melanoma. That is in Phase III. We have two other Phase IIIs in non-small cell lung cancer, and we have a series of Phase IIs just peaking out ready to go into Phase III, depending on what we see with the Phase IIIs that we have out. And so the melanoma readout is based on a Phase II where you added the INT or the cancer vaccine on top of KEYTRUDA, and you saw an impressive reduction in disease relapse-free survival. The other important thing is over 5 years, that was a durable response. So we're very eager to see what that Phase III is because not only it will -- if it's successful, will it be important for melanoma, but it will trigger even more investment in these other tumor types.

In relationship to the PCD data, I think the PCD data is [ 28 ], and there's always chances of having interim analysis that read out early.

Okay. Can I ask about KRAS? You mentioned your KRAS inhibitor. Obviously, especially at the outset, an enormous amount of fanfare around the G12C inhibitors. I think it's fair to say that it's taking a little bit longer to see substantial impact on patients than perhaps had been hoped or at least implied by investor expectations. Where do you see the KRAS target going from here?

So I would tell you that KRAS G12C as a molecule and as a target is critically important in lung. And so this is an important lesson that we constantly learn, which is if you want to go in lung, and you can't move first line with a PD-1, you will not have an impact. The impact of KEYTRUDA or other PD-1s in lung is so profound that you have to be added to that. And the first-generation molecules could not do that. I don't think it will take time for those molecules. If you cannot combine with a PD-1 effectively and be at par of KEYNOTE-189 and better, I think it won't take on. Our 1084, we are enthusiastic. We're moving it in lung because we believe that it can -- here's a pill, you give subcu pembro, early, late, right? That's something that could be really important, both in the early stage, but in the first line. The same thing is true if you want to move it in CRC. If you're going to move it in colorectal cancer, it's fine to have a [ signal ] in second line, third line. But if you cannot combine it within EGFR or cetuximab, you will not have the full impact. So there was a lot of excitement because you got [ a signal ]. But in order to move these things, you need to be able to put it in first line, and you have to have a clear understanding of what it needs to combine with because if it does not combine, you will knock it in first line. If you do not get into first line, you will not have that impact.

Maybe going to a product that's just rolling out now and that's KEYTRUDA subcu or QLEX. So how -- what can -- other than sales, what metrics can investors monitor to see how you're progressing against that goal of 30% to 40% penetration of the KEYTRUDA molecule in a few years?

Yes. So we're really excited about QLEX, our subcutaneous formulation of pembrolizumab and the benefits it can provide patients as Dean just demonstrated in just a very short duration shot, you have been given your treatment for cancer. So what we have with this is a sales level of around $35 million in the fourth quarter of 2025 million. We expect sales to grow modestly in the first quarter this year before we'll see the permanent [ J code ] that we expect at the beginning of April. What we're hearing from both the health care providers as well as patients is in line with our expectations. That is, this is a tremendous innovation. It's an innovation that they need to work through their own operating processes and systems to ensure that it has the relevant formulary decisions. It's also on the electronic health record so that it can be utilized. But we're seeing early utilization already in predominantly patients who are on KEYTRUDA monotherapy or KEYTRUDA in combination with another oral agent. So that's the majority of the current use.

We are, however, also seeing use with IV chemotherapy. And that's largely in the early cancer setting. So the indications we're having thus far is the importance of this innovation the importance, especially when the patients are monotherapy or in combination with an oral agent and the importance in the early-stage cancer setting. So we expect still and have confidence in the 30% to 40% penetration of our overall KEYTRUDA business with adoption here for that patient group. And we will continue to provide insights to our investors as we see this unfold over the coming months and quarters.

GARDASIL, should we expect any major change in trends in 2026?

So we are very proud of the impact GARDASIL is having for the world in helping prevent HPV-related cancers. What we have stated for 2026 is we expect revenues to be roughly stable compared with where we were in 2025. And that's as we continue to really advance the vaccine, especially in the mid adult segment. While we do see in the adolescent segment, some maturation of where we've had penetration in the U.S. and outside of the U.S. So we see this as an important product for the world, an important contributor to Merck's revenue but not a driver of growth.

And we're down to only a few seconds left in the panel. So let me close by asking you each a question, same question, and that is, what do you anticipate will be the biggest change or surprise at Merck in the next decade? Maybe not a surprise to you, but it's a surprise to us.

So maybe where we started, our company really is transforming. And I think what you'll see in this next decade is our company transforming from a position where KEYTRUDA, GARDASIL and Animal Health were the dominant parts of our business to instead be a company that has a diverse set of products, products that are either first-in-class, they're best-in-class or we've innovated around them to bring the next innovation in those therapeutic areas. And as a result, we'll have made a difference in this world, we'll have driven strong growth for our company and returns for our shareholders.

And in Merck Research Labs?

To deliver on that promise.

Okay. That's a tall water. Well, thank you so much. This has been a very interesting conversation.

Thank you for standing by. Welcome to the Merck & Company, Inc., Wawa New Jersey USA Fourth Quarter Sales and Earnings Conference Call. [Operator Instructions] This call is being recorded. If you have any objections, you may disconnect at this time. I would now like to turn the conference over to Mr. Peter Dannenbaun, Senior Vice President, Investor Relations. Sir, you may begin.

Thank you, Shirley, and good morning, everyone. Welcome to the Fourth Quarter 2025 Conference Call for Merck & Company, Inc. Roway, New Jersey USA. Speaking on today's call will be Rob Davis, Chairman and Chief Executive Officer; Caroline Litchfield, Chief Financial Officer; and Dr. Dean Lee, President of Research Labs. Before we get started, I'd like to point out that we have items in our GAAP results such as acquisition-related charges, restructuring costs and certain other items that we have excluded from our non-GAAP results. There is a reconciliation in our press release. .

I will also remind you that some of the statements that we make today may be considered forward-looking statements within the meaning of the safe harbor provision of the U.S. Private Securities Litigation Reform Act of 1995. Such statements are made based on the current beliefs of our company's management and are subject to significant risks and uncertainties.

If our underlying assumptions prove inaccurate or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements. Our SEC filings, including Item 1A in the 2024 10-K, identify certain risk factors and cautionary statements that could cause the company's actual results to differ materially from those projected in any of our forward-looking statements made this morning.

Merck & Company Incorporated, Rabale, New Jersey USA, undertakes no obligation to publicly update any forward-looking statements. During today's call, a slide presentation will accompany our speakers' prepared remarks. These slides along with the earnings release, today's prepared remarks and our SEC filings are all posted to the Investor Relations section of our company's website. With that, I'd like to turn the call to Rob.

Thanks, Peter. Good morning, and thank you for joining today's call. Our company's purpose to save and improve lives guides everything we do. In 2025, we advanced key programs across all phases of development, furthering our mission to deliver transformative medicines and vaccines that will improve health outcomes for patients around the world. I'm very proud of the significant progress we are making. And as we look ahead, we'll remain intently focused on bringing forward breakthrough science and innovation which is the foundation for creating sustainable long-term value for both patients and shareholders.

The transformation of our portfolio is well underway, and momentum is building as we continue to execute on our strategy. In 2025, our business benefited from successful new product launches, the advancement of important clinical programs and the expansion of our respiratory and infectious disease portfolios through the acquisitions of Rona Pharma and Cidara Therapeutics. As a result of this progress, we now have line of sight to over $70 billion of potential commercial opportunity by the mid-2030s, $20 billion more than just a year ago and more than double consensus 2028 peak KEYTRUDA revenue of $35 billion.

While we still have more to do, this meaningful progress further bolsters my already high confidence in our ability to deliver sustainable growth post the KEYTRUDA LOE period. Now turning to our results and initial outlook for 2026. Growth in 2025 reflects demand for our innovative portfolio, including for KEYTRUDA, which continues to benefit more patients with cancer globally, increasing contributions from new launches in cardiometabolic and respiratory as well as vaccines and strong performance of Animal Health.

We're well positioned to achieve commercial success across key products in 2026 while we make important investments behind our new product launches and expanded pipeline, which Caroline will speak to momentarily. Our research colleagues continue to achieve remarkable progress across our broad and deep pipeline. Focusing on a few key events from the fourth quarter; in cardiometabolic and respiratory, at AHA, we presented Phase III results for enlicitide that underscore the practice-changing potential of an oral PCSK9 inhibitor. Cardiovascular disease is the leading cause of death globally, and we look forward to bringing a potential new option to help address the CV epidemic. For winrevere we announced Phase II top line findings from the CADENCE trial that are supportive of its continued development in a different type of pulmonary hypertension. And building on recent momentum in HIV, we shared positive top line results for islatravir in combination with doravirine for treatment-naive adults living with HIV.

Finally, we're pleased that both enlicitide and SAC TMT, our investigational TROI directed antibody drug conjugate. We're granted commissioners national priority vouchers by the FDA, which may expedite review of these important investigational candidates after applications are filed. We recently completed the acquisition of Cidara, which complements our portfolio and builds on our long legacy in combating infectious diseases. MK 1406, formerly CD 388 is a potentially first-in-class long-acting antiviral candidate designed to help prevent influenza infection in individuals at higher risk of developing serious complications.

There is a substantial unmet need for influenza prevention in a large at-risk population and Phase II results were very promising. We believe MK 1406 has greater than $5 billion in revenue potential and can be a meaningful driver of growth later this decade and through the next. We're excited to welcome the Cidara team to our company and look forward to advancing this novel preventative antiviral agent.

Today, our business is anchored by an important set of commercial products that address critical unmet needs. We're also executing on the transformation of our portfolio with initial launches from over 20 potential new growth drivers to have the promise to advance the practice of medicine and change patient lives. Ten of these programs could be substantially clinically derisked over the next 2 years and represent the majority of our $70 billion of nonrisk-adjusted commercial opportunity by the mid-2030s.

And our long-term outlook is further bolstered by the strong growth we expect in our Animal Health business by the many early phase programs that will enter Phase I in the near term and through additional potential science-led disciplined and value-enhancing business development. We're entering a particularly robust period of first-time Phase III data readouts for novel candidates. In 2026, these include islatravir combined with lenacapavir, potentially the first once-weekly oil treatment regimen for people living with HIV. MK-3000, potentially the first new mechanism of action in 2 decades for patients with certain retinal diseases. And torsokibar, where we expect to see Phase III results in ulcerative colitis as well as Phase II data in other autoimmune diseases.

There is an even richer array of expected readouts in 2027 and including Phase III results for SAC TMT, which we believe is a differentiated Trop2 ADC. For IDXD, our B7-H3 antibody drug conjugate being studied in small cell lung cancer and other tumor types for NK-1406 as well as for a number of other important programs. In summary, we're successfully executing multiple product launches, making significant clinical advancements and augmenting our pipeline with strategic business development. We're also making the necessary investments that will sustain our success over the long term. Our progress and momentum positions us to continue delivering on our purpose for patients and create durable value for shareholders.

I want to recognize and thank our global teams for their commitment. While there is more to do, the actions taken, the progress we've made and our continued disciplined execution provide me with strong confidence that we're well positioned for our next chapter of success. With that, I'll turn the call over to Caroline.

Thank you, Rob. Good morning. As Rob noted, in 2025, we made meaningful progress in benefiting patients and customers around the world with our portfolio of innovative medicines and vaccines. Our business delivered growth driven by continued strength in oncology and Animal Health as well as increasing contributions from new product launches. These results demonstrate the enduring strength of our business and give us confidence in our outlook as we enter a period with many new launches. Our commercial and operational execution enable us to invest in discovering, developing and launching the next generation of innovations, which will drive long-term value for patients, customers and shareholders. .

Now turning to our fourth quarter results. Total company revenues were $16.4 billion, an increase of 5% or 4% excluding the impact of foreign exchange. The following revenue comments will be on an ex-exchange basis. In oncology, sales of the KEYTRUDA family of products, which includes KEYTRUDA and KEYTRUDA Q increased 5% to $8.4 billion, with global growth driven by robust uptake in earlier-stage cancers and strong demand from metastatic indications, utilization in tumors that primarily affects women, including breast, cervical and endometrial cancers, continues to be a key contributor to growth.

In addition, we saw increased use of KEYTRUDA in combination with Padcev in locally advanced or metastatic urothelial cancer. In the U.S., growth was negatively impacted by approximately $200 million due to the timing of purchases. We are pleased with the positive provider feedback following the recent launch of KEYTRUDA QLEX. As expected, sales in the quarter were $35 million. We look forward to having a greater impact on patients and health care systems following implementation of a permanent J code in the U.S., which we continue to expect to occur in the beginning of April. Our broader oncology portfolios achieved another quarter of strong growth. Notably, Welly rec sales increased 37% to $220 million, predominantly driven by increased use in certain patients with previously treated advanced renal cell carcinoma in the U.S. as well as continued uptake from ongoing launches in certain international markets.

We look forward to potentially reaching more patients with renal cell carcinoma, following positive data from the Light Spot 11 and 22 studies. In vaccines, GARDASIL sales were $1 billion, a decrease of 35% driven by lower demand in China and Japan. Other international markets grew 8%, benefiting from the timing of purchases. In the U.S., sales grew 7%, largely due to price. In pneumococo, the Capexes launch continues to progress well, with sales of $279 million, driven by demand from both retail pharmacies and nonretail customers, including uptake from increased seasonal immunization activity in the U.S.

In RSV, Inflonzia sales were $21 million. Initial uptake has been constrained by a lower-than-expected infant immunization rate coupled with high levels of total RSV monoclonal antibody inventory in the market. In cardiometabolic and respiratory, WINREVAIR continues to have a positive impact for patients with pulmonary arterial hypertension. Global sales was $467 million, a reflection of the continued strong demand for this important treatment. In the U.S., more than 1,500 new patients received a prescription and over 27,000 total prescriptions were dispensed.

We also saw an increase in the proportion of patients whose background therapies do not include a prostacyclin. Outside the U.S., we continue to progress with securing approvals and reimbursement. We are excited to build upon the successful U.S. launch of otuver, a maintenance treatment for adults with COPD with a novel mechanism of action. In the quarter, sales were $178 million, reflecting revenues following the acquisition of Verona on October 7. We delivered strong growth in new patient starts and total patients treated. We also saw physicians prescribe Otuver to more of their patients and an increase in the total number of prescribing physicians.

As a reminder, we expect seasonality in the early part of the year as Medicare deductibles are reset. We are making investments to maximize the ongoing launch in the U.S. and look forward to benefiting more adult patients with COPD. Our Animal Health business delivered another quarter of strong growth, with sales increasing 6%. Livestock sales grew 9%, driven by higher demand across all species. Companion animal sales were flat as growth from new product launches was offset by a reduction in vet visits. I will now walk you through the remainder of our P&L, and my comments will be on a non-GAAP basis.

Gross margin was 79.7%, a decrease of 1.1 percentage points due to higher inventory reserves, partially offset by favorable product mix. Operating expenses decreased to $6.8 billion, a charge of $150 million related to an agreement with Dr. Falk Pharma to acquire sole global rights to MK-8690 was lower than the $700 million in business development charges a year ago. Excluding these charges, operating expenses were flat reflecting an increase in investments in support of our innovative pipeline and key growth drivers offset by the benefits of our multiyear optimization initiative.

Other expense was $226 million. Our tax rate was 15.4%. Taken together, earnings per share were $2.04. Now turning to our 2026 non-GAAP guidance. We expect revenue to be between $65.5 billion and $67 billion representing growth of 1% to 3%, including a positive impact from foreign exchange of approximately 1 percentage point using mid-January rates. Our gross margin assumption is approximately 82%. Operating expenses are assumed to be between $35.9 billion and $36.9 billion which includes a onetime charge of approximately $9 billion related to the acquisition of Cidara.

As a reminder, our guidance does not assume additional significant potential business development transactions. Other expense of approximately $1.3 billion includes financing costs for Cidara and Verona. We assume a full year tax rate between 23.5% and 24.5%, which reflects the nontax deductible onetime charge for Cidara. We assume approximately 2.48 billion shares outstanding. Taken together, we expect EPS of $5 to $5.15 with a midpoint of $5.08, including a positive impact from foreign exchange of approximately $0.10 using mid-January rates.

Excluding approximately $3.65 per share related to the upfront charge for the acquisition of Cidara as well as $0.30 per share of ongoing costs to advance MK-1406 and finesta transaction, our midpoint would be $9.03. As you consider your models, there are a few items to keep in mind. We expect to deliver growth in 2026 driven by increasing contributions from our new launches as well as continued strength in oncology and Animal Health, despite a headwind of approximately $2.5 billion from generic competition, IRA price setting and the restructured agreement for Caselli go. Generic competition primarily impacts the Januvia family of products, Radeon and deficit.

We also expect significantly lower sales of Lagebrio due to continued soft demand some growth, including new product launches and our robust pipeline. And with the goal of increasing it over time. Business development remains a high priority. We are well positioned to pursue additional transactions when science and value align. Our guidance assumes approximately $3 billion of share repurchases, and we remain committed to not having excess cash build on the balance sheet.

To conclude, we entered 2026 with confidence in the outlook for our business, driven by global demand for our innovative medicines and vaccines, including the exciting progress of our many launches and upcoming clinical milestones from our promising pipeline. We maintain our longstanding commitment to bringing forward medically significant innovations that will enable us to deliver value to patients, customers and shareholders well into the future. With that, I'd now like to turn the call over to Dean.

Thank you, Caroline. Good morning, everyone. Progress continues across programs spanning multiple therapeutic areas. Today, I will provide updates across cardiometabolic and respiratory, infectious disease and oncology programs, then conclude with a summary of highlights from 2025 and upcoming milestones for this year.

Starting with advancements across our cardiometabolic and respiratory pipeline and programs, enlicitide, our investigational oral PCSK9 inhibitor has been designed to deliver antibody-like efficacy while offering a simple, once-daily oral treatment option with the potential to help address the CV epidemic.

Data from 2 Phase III studies evaluating elicitide for the treatment of adults with elevated LDL cholesterol were presented at the American Heart Association Scientific Sessions in November. In both the core reef lipid study, which included a broad population of adults with or at risk for atherosclerotic cardiovascular disease on background lipid-lowering therapies or with statin intolerant, and the Coral Reef AFH study in adults with Familia, heterozygose and hypercholesterolemia, enlicopide demonstrated statistically significant sustained reductions in multiple atherogenic factors, including LDL-C, Apo B, non-HDL-C and Lp(a).

The findings from the core reef HEFH were published in the Journal of the American Medical Association and from core reef lipids have been accepted to the New England Journal of Medicine. In addition, positive results of the third Phase III trial core reef add-on, evaluating elicitide comparing to other oral nonstatin therapies in adults with hypercholesterolemia and treated with a statin will be presented at the American College of Cardiology Congress in March.

The Phase III CORE REIT outcome study is ongoing and fully enrolled. For vinrevere, we continue to make progress on our global regulatory strategy. Last month, the European Commission approved an expanded indication in adults with pulmonary arterial hypertension with WHO functional Class II, III and IV based on the Phase III ZENITH study. We are continuing to evaluate vinrevere in an additional indication associated with progressive vascular remodeling and resistance. The Phase II Cadence study met its primary endpoint, achieving statistically significant and clinically meaningful reduction of pulmonary vascular resistance compared to placebo in adults with combined post and precapillary pulmonary hypertension due to heart failure with preserved ejection fraction.

These findings support proof of concept, which will inform a Phase III program in this population. Detailed results will also be presented at the American College of Cardiology Congress in March. Next, infectious disease. Last month, we completed the acquisition of Cidara Therapeutics. The scale of the ongoing seasonal flu outbreak in the Northern Hemisphere reinforces the threat posed by Influenza, the corresponding burden on health care systems and importantly, the need for improved prevention strategy, specifically for those individuals at high risk of serious complications.

The Phase III ANCHOR study evaluating MK-1406, a potentially first-in-class long-acting preventative strain agnostic antiviral with a differentiated mechanism of action, completed enrollment in November in the Northern Hemisphere. In parallel, we will enroll participants in the Southern hemisphere to ensure the collection of a robust data set spanning a broad patient population, including adults who are immunocompromised and to capture additional data on diverse circulating strains.

Furthermore, it is also important for the study to encompass those who have been vaccinated against the flu and those who have not. Turning to HIV. In November, we announced positive top line results for our investigational once-daily, single-tablet 2-drug regimen of doravirine and ezlosevir and next-generation nucleoside analog leveraging translocation inhibition from a Phase III study in previously untreated adults with HIV 1 infection. This is the first 2-drug regimen without an HIV integrated strand transfer inhibitor to demonstrate noninferior efficacy and safety versus the broadly used 3-drug entry-based regimen, Biktarvy. Based on its potent antiviral properties and barrier to resistance, it is our ambition that islotevir will serve as a novel anchor medicine across multiple 2-drug treatment regimens providing new daily and weekly options for people living with HIV.

Detailed results will be presented at an upcoming medical congress.

Moving to oncology. Data continue to demonstrate KEYTRUDA's impact in treating a wide spectrum of cancers. In bladder cancer, there were 2 recent notable developments. First, the FDA approved KEYTRUDA and KEYTRUDA Culex each in combination with padcef as neoadjuvant treatment and continued after cystectomy as adjuvant treatment for adults with muscle invasive bladder cancer who are ineligible for cisplatin containing chemotherapy based on Phase III KEYNOTE-905 trial.

This is the first PD-1 inhibitor plus antibody-drug conjugate regimen approved for this population. Second, we announced positive top line results from the Phase III KEYNOTE-B15 study. The combination of KEYTRUDA plus padcev, given as neoadjuvant and adjuvant treatment demonstrated statistically significant and clinically meaningful improvements in event-free survival, overall survival and pathologic complete response rates versus neoadjuvant chemotherapy and surgery.

This is the first and only perioperative immunotherapy plus ADC regimen shown to extend survival for cisplatin eligible patients with muscle invasive bladder cancer. Detailed results will be presented later this month at the ASCO Gentiourinary Cancer Symposium. Together, these regimens have the potential to offer patients with muscle invasive bladder cancer who are either eligible or ineligible for cisplatin chemotherapy, a KEYTRUDA-based option. Three additional Phase III studies are ongoing evaluating KEYTRUDA across different stages of bladder cancer, including KEYNOTE-992, KEYNOTE-866 and Keynote-676.

In collaboration with Moderna, we recently announced 5-year follow-up data for the Phase IIb Keynote-942 study evaluating intersabaran autogene, an individualized neoantigen therapy candidate in combination with KEYTRUDA in patients with high-risk Stage III or IV melanoma following complete resection. In the follow-up analysis, the study demonstrated a sustained improvement in recurrence-free survival with a 49% reduction in the risk of recurrence or death compared to KEYTRUDA alone, building on the previously announced primary and 3-year analysis from the trial.

The Phase III INTERPATH-001 trial in adjuvant melanoma is ongoing and fully enrolled. In November, the European Commission approved a subcutaneous injection of pembrolizumab and veraloranadase alpha market in the EU as KEYTRUDA SC for use in all 33 KEYTRUDA indications for adult patients. It is the first and only subcutaneous immune checkpoint inhibitor in Europe, that can be administered in 1 minute, every 3 weeks or in 2 minutes every 6 weeks. The availability of more rapid subcutaneous pembrolizumab administration is being integrated into our clinical development programs.

CANALI-007, a Phase III study evaluating colderasib an investigational oral selective KRASG12C inhibitor in combination with KEYTRUDA culex for the first-line treatment of patients with KRAS G12C mutant advanced or metastatic nonsquamous non-small cell lung cancer. In December, at the American Society of Hematology Annual Meeting, we highlighted progress across our hematology pipeline with positive data spanning multiple candidates, including MK-1045, an investigation of CD19 CD3 T cell engager in adult with relapsed or refractory B-cell acute lymphoblastic leukemia.

Naphtabrutineb, an investigational noncovalent BTK inhibitor in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma, ambomademsta, an investigational LSD1 inhibitor in patients with polycythemia vera who are resistant or intolerant to cytoreductive therapy. In addition, there are 2 ongoing Phase III studies evaluating modest in essential thrombocythemia and orphan disease. 2025 was marked by significant pipeline progress, including positive data announced from 18 Phase III trials and the initiation of 21 Phase III trials spanning cardiometabolic and respiratory, immunology, infectious disease, oncology and ophthalmology. We also secured regulatory approvals across therapeutic areas, including in oncology, KEYTRUDA CLEC and additional KEYTRUDA-based regimen, including in patients with cisplatin-ineligible MIBC and locally advanced head and neck squamous cell carcinoma.

In infectious disease emplanzia are long-acting monoclonal antibody for the prevention of respiratory syntictal virus, lower respiratory tract disease in infants born during or entering their first RSV season. And in cardiovascular, the label update for vinrevere River in PAH. Finally, we continue to deliver on our 1 pipeline strategy by leveraging our clinical expertise and robust business development capabilities. The acquisition of Verona Pharma and Cidara Therapeutics further strengthen our pipeline and bring forward promising candidates with the potential to serve areas of significant unmet patient need.

Building on our momentum in 2025, we anticipate a series of milestones across multiple therapeutic areas in the coming months, including in oncology, the February 20 PDUFA date for certain patients with platinum-resistant recurrent ovarian cancer based on the KEYNOTE-B96 trial. Presentation of detailed findings at ASCO GU 4, Welareg, our first-in-class oral HIF-2 alpha inhibitor across adjuvant and certain types of advanced renal cell carcinoma based on the Phase III Light Park 11 and 22 trials and for KINO B15 and cisplatin eligible patients with MIBC.

In HIV, the April 28 PDUFA date for doravirine and islatravir, a once daily oral 2-drug treatment regimen and top line data from the Phase III ISL1 and 2 trials evaluating izlogivir and lenacapavir as a once-weekly oral 2-drug treatment regimen in collaboration with Gilead. In cardiometabolic and respiratory, the presentation of detailed results at ACC in March for vinerevere from the Phase II Cadence study in a subset of pulmonary hypertension due to left heart disease. And for elicitide from the Phase III Core REF add-on trial.

In immunology, data for Tuliocopar, our TL1A inhibitor based on the Phase III ATLAS UC trial in ulcerative colitis and Phase II ATHENA study in FSC ILD. Finally, in ophthalmology, data from the Phase III Brunella study of MK 3000 our novel win agonist being evaluated in diabetic macular edema and the Phase II RORA study of MK-8748 are potential first-in-class tie-2 agonist VEGF inhibitor being evaluated for the treatment of certain retinal disputes.

We continue to advance our diversified pipeline with a focus on executing with speed and rigor I look forward to providing further updates through 2026. And now I turn the call back to Peter.

Thank you, Dean. Surely we're now ready for Q&A. We have a hard stop today at 10:00 a.m. So I'd like to request that analysts limit themselves to 1 question, please.

[Operator Instructions] Our first question comes from Mohit Bansal with Wells Fargo.

And congrats on all the pipeline progress. Maybe if you can double-click on the CD388 asset and potential for interim here. So the flu season appears to be strong this season. So it would seem like that event rates may be occurring ahead of the plan in the ANCHOR trial. But would love to understand your thoughts around running the full trial? Is it based on generating robust data across 2 geographies, 2 seasons or anything you're seeing from the event based point of view ongoing trial? And should we expect an interim disclosure in March or after March or not?

This is Dean. I do think your point about the relatively severe season, especially for many of us in the Northeast for the flu demonstrates how important this small you could be. We have completed enrollment in the Northern Hemisphere. I want to emphasize, as I said in the prepared, we are in parallel recruiting in this southern hemisphere -- this is an event-driven trial. I want to have the right trial size, I want the powering of the assumptions. But most importantly, I need to make sure that I have strong data throughout a series of subpopulations that will be important for the future label. So at this time, we have not spoken communication plans following IA, but we're excited about this first-in-class once per season strain agnostic antiviral agent, which I think will have increasing need as the year go by.

Our next question comes from Akash Tewari with Jefferies.

Are there any plans to explore that GMT in a first-line and CLC setting in PD-1 low expressing patients or head-to-head against the KEYNOTE-189 regimen given some of the emerging data you're seeing out of China. I'm kind of curious why your coq2 development strategy seems to be relatively conservative versus what AstraZeneca and Daiichi are exploring, especially if you have a differentiated asset?

Thank you very much for that question. So as we've said repeatedly, we think this is a work horse ADC. We also think that I look at the HER2 field and -- so there and I go, you just changed the linker and the payload and all of a sudden, you have very different readouts from an antibody drug conjugate. And so we think sec TMT has a potential to be best-in-class TROP2 directed ADCs. What I would say when you talk about the ambition, I mean, we have 16 Phase III studies, 11 that we view our first-in-class, the other 5 are differentiated.

So I just I think we're very ambitious with our SAC TMT program. In relationship to the specific question in relationship to non-small cell lung differentiated approaches to others. But most important, we also have it in tissue tugs and tumor types where we are hoping to be first. So I would challenge a little bit the characterization that we do not have a robust and ambitious program. We have 16 Phase III studies.

Thank you Akash.

Our next question comes from Alex Hammond with Wolf Research.

So consensus currently anticipates KEYTRUDA's U.S. LOE to occur in '28. However, Merck SEC filings suggest potential for 2 additional patents that expire in '29. So I guess, how should we model the IP run rate for KEYTRUDA? And how should we think about the timing associated with QX ramp prior to KEYTRUDA IV biosimilar introduction?

Yes. Thanks for the question. As you look at the intellectual property situation for KEYTRUDA. There was -- when the original invention was filed for approval with the patent office, there were actually 4 patents that made up the patent estate that was the original innovation. One of those is the compound patent which expires December of 2028. 2 of those, one a method of making patent actually is extended out to May of 2029. And the second one, a method of use patent goes out to November of 2029. And so as we looked at this initially, we were conservative in our assumptions and always based off the compound patent, always though with the intent that we would defend the entire patent estate.

I think what has evolved over time is that this case law has emerged our confidence that we will be able to defend those additional 2 patents has grown. And thus, there is a potential that you're going to see protection actually make it through either May or November of 2029. For planning purposes, we continue to assume 2028 because I think that's a conservative assumption, and we'll have to see where it goes. And I would also remind you that we do face the IRA as of the beginning of 2029.

As we think about the QX adoption, we continue to think we're going to see 30% to 40% adopted as you get out to 2028 and we will drive that as high as we can. And as you know, we have priced this to drive for the adoption from KEYTRUDA IV to QLC. So that will continue. That strategy is underway. And frankly, whether it's '28 to '29 does not change the strategy we're following.

Next question pls.

The next question comes from Evan Seigerman with BMO Capital Markets.

I want to touch on the HIV data that you were discussing. Can you just contextualize the importance of a dual regimen versus the standard of care bactgravir of atarvy? And kind of what's the feedback in more broadly unmet need for a dual regimen versus the standard of care triple.

Yes. So thank you very much for that question. So as you highlight, we're really excited about is LotiVer because we really think it's a next-generation cleoside analog. So leverage is a unique mechanism of translocation inhibition that gives it high potency and high degree of resistance. In relationship to 2 drugs and 3 drugs, there have been always a need for different options you see it already, there is a 2-drug regimen out there in relationship to the 3 drugs, and there have been considerable switching that occurs in this patient population just as a general rule. So the ability to send a different sort of repertoire of compounds, especially if you can spare the integrase would be potentially very important for some people, that's often viewed in light of metabolic and long-term issues with HIV treatment.

So I think there will be an excitement of having a 2-drug combo without an insti backbone. Equally important, I just want to make sure is we're driving a 2-drug regimen for the first Q weekly offering and we have won with our partner, Gilead, and we have another 1 with Uline. So I think all of those, that 2 drug for daily, but also that 2 drug for weekly is something -- there's no weekly 3 drug or 2 drugs.

So we think there will be an important opportunity for patients to experience a 2-weekly option. And finally, we have a q monthly prep or we don't -- there is no other Q monthly oral prep. Although it's not islotivir, it's a related compound, which is MK8527.

Next question comes from Steve Scala with TD Cowen.

A bigger picture question for Rob. But in 2025, Merck achieved the sales guidance it provided to start the year and you dealt with the GARDASIL pressures all year long. But in any year for any company, there will be some challenges. So this is likely to be more the rule rather than the exception. And Merck has some growth products, too. So in what might be a typical year, Merck grew minimally. And in 2026, you are again looking for minimal top line growth with the KEYTRUDA LOE still a couple of years off. .

So the question is, is this what we should expect from Merck going forward, a company that grows modestly in good times and significantly pressured in less good times or can Merck achieve sustainable, strong sales growth in the decade ahead despite what will be inevitable challenges?