Merck & Co., Inc. (MRK) Earnings Call Transcript & Summary

Welcome to the Merck & Company Inc. Rawa 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 AID2026 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. It 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 ILN 1 and ILN 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 have 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. Phil. 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 Liz Rhee. Liz?

Thank you, Elias. Good morning, everyone. I'm so pleased to be here this morning to share with you the data we presented at ASE 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 lunivirine 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 ILandND-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 PA 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's snapshot analysis. Secondary endpoints included rates of viral suppression, CD4 cell count changes and treatment discontinuations. Results for -- in ION-1 for islatravir and lenacapavir show that non-inferior efficacy was achieved against the comparator istegravir 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 ezlotivir or lenacapavir in this trial. These strong efficacy results support the potential for logabilicapavir as the first complete once-weekly oral treatment regimen for HIV. In Islend-2, the second Phase III trial, we also evaluated islatravir 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 to randomize to these 2 regimens. And similar to Islend-2, azatalenocapavir 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 is logabilenecatavir than with their standard of care therapies that they had come in on. And as well found as logic alenacapavir to be less of a burden compared with daily oral. We were very satisfied and we are very pleased to see the satisfaction rates. In addition, safety across Island 1 and Island 2 were consistent. Islatravir lenacapavir was well tolerated with a safety profile comparable to etegravir/FTC TAF and standard of care regimens. There were no clinically meaningful changes in lymphocytes, CD4 counts or body weights 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 and [indiscernible] to become the first 1 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 resistant signals and safety and tolerability comparable with the control arms. We look forward to submitting isltravir and aleicapivir 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 ilanivarine. 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 everilogically 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 FCC Pat. There were no participants on the islatravir and 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 this trial in islatravir and ulonivirine was generally well tolerated. There were no new safety concerns identified. In addition, the adverse event profile was comparable to bictegravir FTC has, and we observed no meaningful effect on lymphocyte counts or CD4 accounts. Based on these results, we plan to advance islatravir and ulonivirine into a comprehensive Phase III program. The sempra 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 ZYMfORIA #1 and #2 are anticipated to open in the first half of 2027. Sofora #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 or 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 anti-retroviral 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. Avino, our newly approved once-daily oral treatment marks the beginning of a broader portfolio strategy. Avinzo is the first and only non-entity tenofovir free once-daily complete 2-drug regimen to demonstrate noninferior efficacy in a head-to-head Phase III trial versus 3-drug regimen F/TAF. Avinza 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 Envinzo, 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 tablet. I will address each of these opportunities in turn. We are particularly excited about the potential for Islend 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 sale 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 as a molecule developed specifically for prevention. The Express of 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 Avinza, Iselin, IsoLo and Alimatravir creates a meaningful long-term opportunity. We see an opportunity of greater than 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 ISO 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 Island 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 planned ISOuLu/SIMPORIA Phase III program in the treatment 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 1 and then Liz can take the second one. With respect to the CD4 content 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 Alen 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 SYMFORIA trials, let me turn it over to Liz.

Sure. Thanks, Eliav. So for the Velogica suppressed indication, we are planning 2 studies, as I indicated earlier, SIFI and SYMFORIA to both of these studies in terms of primary endpoints would follow FDA guidance with the primary endpoint being those with viral load greater than equal to 5 analyzed by the FDA snapshot. We would also be looking carefully at safety, of course, in these studies. And I think with INFRA number 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 the studies in the first half of next year. The details of the secondary endpoints and time lines of the trial, 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.

But just to make -- to be clear, I mean, I think the SYMFORIA studies are going to be very important. -- addition on the Q week regimen. Just to remind everyone, we'll have both treatment experience 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 QE 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 are more set with them.

Our next question comes from Mohit Bansal with Wells Fargo.

My question is regarding some feedback we get from both experts as well as Glen is also talking a little bit about is that integrase inhibitors are considered the gold standard of treatment in HIV as of now, I mean if you look at the guidelines, there are like 4 integration inhibitor combos there. But your tutor combo does not include integrated inhibitors just yet. How do you think about when you agree with that? Number two, how do you think about the positioning of your [indiscernible] based combinations or is there a subpopulation out there that could actually benefit from these combinations rather than this being a frontline agent?

First of all, as you know, we were the discoverers of the integrase class, but I think that it's important to have options for patients -- these options are very, very -- this is a very long-lasting disease requires many, many different options. I'll turn it over to Liz to talk a little bit about how we've -- what we've heard and what we're thinking about in terms of the ins free regimens.

Right. So the feedback we've heard is that there is a need for options for patients that are regimens that don't contain inverse inhibitors. Remember, this is a chronic infection. People are aging now with HIV, meaning that they have carried a cytosis sometimes for decades, 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 H and deal with comorbidities, there is a 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, drug-drug interactions as people are taking more medicines for their comorbidities. So Eliav, 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 integrates is not going to solve every problem for them.

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

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

I'll ask Brian and Greg to address.

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 4 potential therapies. One is approved in the marketplace today with Avendo and then 3 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. But maybe, Greg, if you want to give a little bit more detail to it.

Yes. 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 I -- it really gives us growing confidence in our potential to achieve that greater than $5 billion revenue by the mid-2030s. I think 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 2 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 Q weekly orals will have a strong place within that segment. Each of these assets, including alimatrevir in the prep space will be contributors to that overall $5 billion number. And I think alimatrevir 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 alumatrivir in the context of a market that's actively organizing around injectable who the target patient population is how you're thinking about that window before yes and altitude, establish those the prescriber and infrastructure relationships, what the access and pricing strategy may also look like in both the high income and high burden markets.

Thanks for the 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 had to say what was just a wow moment for everyone at the meaning was alimatrivir. We could not get away from anyone who wanted to say something about alimatevir, to think about alimatravir as part of their treatment regimens and so on. Maybe I'll turn it over to Greg to talk a little bit about his impressions.

Thanks, Eliav. And I would start by saying that despite the availability of a number of highly effective prep alternatives today, either daily oral or injectable. 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 1 in 5 globally. And there can 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. It -- in 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.

Great. Thanks, Alex.

Our next question comes from Geoff Meacham with Citibank.

Another one on the weekly oral, I just wanted 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 Q regimens. And then I'll ask Brian and Greg to talk about the commercial potential. Liz?

Right. So for both of the oral weekly regimens, istralapir and linicapivir as well as easier later bringing. 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, may need a window to catch up essentially. So that week of forgiveness means that if you get 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 Keane D. But maybe I'll ask Brian and Greg to talk about the other piece.

Maybe just at a really high level, and then I'll pass it over to Greg for a bit more detail. Now we know, again, in the treatment space, as I mentioned before, this is 1 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 week the option, but it's exciting to be bringing to, to be quite frank. And so maybe Greg can give a bit more details about the 2 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. I start with sale, 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 regimens. 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 is a lens because it brings together 2 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 IzlUlo, this is also a highly effective program based on our Phase II data so far. -- effective with a small 2-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 -- also importantly, there's no loading dose associated with Isle. 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 a once-weekly will persist beyond the launch of [indiscernible] and we see is izulo 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.

Great. Thank you, Geoff.

Our next question comes from Vamil Divan with Guggenheim Securities.

So maybe 2 follow-ups on one, just on the comments you were just making around ISOs. So I appreciate some what you said there on the benefits that YUGO may provide in terms of no loading dose, smaller pill, favorable DDIs. What about the other way around, if both of them are available, what would be the benefits of Isola 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 CRE 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 that created a $5 billion number.

Thanks so much, Vamil. Let me take the first, and then we can talk about the commercial elements. So it's exciting to have atrial lenacapavir as the first drug because lenacapavir safety profile and efficacy profile are well known and understood. They're part of a lot of lenacapavir as 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 the islatrapri and [indiscernible] cap, I think, will be an excellent first option and a continued option over the course of the years along with the letabirliniverine. So if I could switch to Greg.

Yes. 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 2 assets. I think one is important. The first asset actually comes with the power of 2 organizations that have been in this space for a long, 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 2 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.