Hello, everyone. Welcome to today's call and webcast. The presentation was sent to our distribution list by email, and you can also find it on gsk.com. Please turn to Slide 2. This is the usual safe harbor statement. We will comment on our performance using constant exchange rates or CER and excluding COVID solutions, unless stated otherwise. Please turn to Slide 3. Today's call will last approximately 1 hour and 15 minutes. With the presentation taking around 40 minutes and the remaining time for your questions. Our speakers today are Emma Walmsley, Luke Miels, Julie Brown, and David Redfern, who will be covering HIV in the absence of Deborah Waterhouse, who's recovering from a successful medical procedure. And Tony Wood will be joining us for Q&A. Please ask only one to two questions so that everyone has a chance to participate. Turning to Slide 4. I will now hand the call to Emma.

Thank you, Jeff, and welcome to everyone joining us today. Today, we are reporting our 2024 results and providing you with updates on our growth outlooks, investment plans, and focus on improving shareholder returns. Please turn to the next slide. 2025 will mark three years since the demerger and the creation of GSK as a new dedicated biopharma company for patients and for shareholders. The demerger enabled a fundamental restructure of GSK and its balance sheet, bringing new capacity to invest in growth and to deliver returns to shareholders. Three years on, I'm pleased to say that we've seized this opportunity and made significant progress, building a strong track record of performance delivery. Specialty medicines and vaccines now dominate our reshaped portfolio and pipeline. Our long-term outlooks have consistently improved alongside the quality of our innovation. And we've delivered sustained year-on-year sharper operational performance, underpinned by a stronger balance sheet. This all points to GSK having the platform to deliver sustained profit growth and returns in the short, medium, and long term. Next slide, please. Our 2024 performance demonstrates the transformation of the business. Sales grew 8% to over £31 billion, with strong growth and increasing contribution from Specialty medicines more than offsetting headwinds in vaccines. Core operating profit was up 13% and core EPS was up 12%. This level of performance delivered two upgrades to guidance in 2024 and supports the increased dividend of 61p per share announced today. I'm also pleased to report that we maintained good progress in our six priority areas to build trust, not least retaining a leadership position in the Access to Medicine Index, but we've been placed first or second in the industry since its inception in 2008. And of course, during the year, we also resolved the Zantac litigation prioritizing shareholder interests.…

Thanks, Emma. Please turn to the next slide. As Emma highlighted, overall sales for the year were up 8%, with strong growth from Specialty and General medicines, more than offsetting short-term headwinds, primarily in the U.S. to our vaccines business. Next slide, please. Specialty Medicines continues to show excellent momentum and pipeline progress. And as Emma said, it's now expected to be over half our business by 2031. In 2024, specialty grew 19%, with strong performances across all therapy areas. Respiratory immunology products were up 13% in the year. Nucala, our anti-IL-5 biologic treatment grew 12%, driven by strong performances in Europe and international. Benlysta our treatment for lupus was up 14% in the year, with strong demand across all regions. In oncology, sales almost doubled in the year. Zeluja grew 17% with strong growth across all regions, driven by sustained increases in patient demand. Jemperli sales more than triple in 2024, benefiting from increased patient uptake in the U.S. following FDA or comers approval for primary advanced or recurrent endometrial cancer, and we received EMA all come as approval in January this year. Ojjaara sales increased more than 10x in the year, largely driven by continued strong uptake in the U.S. Contributions from Europe and International are also increasing following launches in the U.K., Germany and Japan, and we expect further launches in 2025. David will cover HIV shortly. We expect the excellent momentum in our Specialty Medicines portfolio to continue in 2025 with sales growth of low double-digit percent, while absorbing the IRA impact. Next slide, please. Looking at what's next in Specialty, in RI&I, we are targeting a major new indication for Nucala to treat COPD following positive headline results from our Phase 3 MATINEE trial. COPD affects more than 300 million people globally and is the…

Thank you, Luke. HIV sales continued to deliver strong growth, up 13% for the full-year, with Q4 delivering our ninth consecutive quarter of double-digit growth. Growth in 2024 was driven by strong patient demand for our oral two-drug regimen, Dovato up 27% and long-acting injectables, Cabenuva and Apretude, which reached £1.3 billion of sales and contributed more than 50% of total growth. This resulted in a 2 percentage point increase in global market share compared to the prior period. Cabenuva, the first and only approved complete long-acting injectable regimen for the treatment of HIV grew 47% to over £1 billion of sales in 2024. Growth was driven by strong patient demand across the U.S. and Europe of 70,000 people living with HIV now benefiting from this transformative medicine globally. In January, we announced European Commission approval for use in adolescents. This marks an important step in bringing this medicine to younger people in line with our commitment to leave no person living with HIV behind. Apretude, the first and only approved long-acting option for HIV prevention delivered sales of nearly £300 million in 2024, continuing its strong growth trajectory at 93%. With 99% effectiveness, we are confident in its strong efficacy, safety and overall tolerability. In 2024, of the 13% growth, 10% was volume with the remainder favorable in-year pricing dynamics. In 2025, we anticipate sales growing by mid-single-digit percentage, supported by ongoing growth in volume, partly offset by pricing headwinds with the introduction of the Inflation Reduction Act which we expect to be £150 million to £200 million impact. The potential for the long-acting market remains significant with the market today for treatment and PrEP together worth more than £22 billion, with treatment accounting for around 90% of this and we believe treatment will continue to be the much larger market going forward. Next slide, please. Our pipeline is founded on integrase inhibitors or INSTIs, the gold standard of HIV treatment and prevention due to their potency, long-term tolerability and high barrier to resistance. We have a clear road map to deliver more long-acting innovation with three new INSTIs in development and five planned launches by the end of the decade. In December, our registrational study for cabotegravir four monthly long-acting injectable PrEP began and we are on track to start our registrational study for every four month long-acting injectable treatment this year. Early data on assets with the potential for six monthly dosing will be available in 2025, including selected presentations at the CROI Congress in San Francisco in March. We are on track to confirm in 2026, the assets that will deliver sixth monthly dosing. For PrEP, this will be one of three long-acting INSTIs and for treatment one of those INSTIs in combination with our BNAV-N6LS or our capsid inhibitor. As pioneers in long-acting injectables, we are confident we have a strong and innovative pipeline to secure and deliver future competitive performance. With that, I will hand back to Luke.

Thanks, David. Turning to vaccines. Total sales were £9 billion, down 3% in the year, largely due to lower sales of Arexvy in the U.S. Overall, Arexvy continues to be the market leader in the U.S. with around 10 million adults now protected. However, demand for the vaccine was lower in 2024, following new ACIP recommendations, a late RSV season and an unfavorable comparison to launch stocking in 2023. Going forward, we continue to assume no revaccination or expansion of age cohorts in 2025, but we do expect both in time, given the protection Arexvy can offer against RSV. Outside of the U.S., Arexvy is now launched in 36 markets, and we are seeing good momentum in uptake with national recommendations in 17 markets and national reimbursement programs in six and we expect more this year. Moving to Shingrix. Sales grew 1% in the year, with growth in Europe and international offsetting lower sales in the U.S., whereas anticipated, the pace of penetration is slowing. The U.S. immunization rate at the end of the third quarter was 40%, up 5 percentage points in line with our expectations for around 3 to 5 percentage points per year. Ex-U.S. growth was driven by higher uptake across European countries and a national immunization program in Australia. Shingrix is now launched in 52 countries, and the average immunization rate across the top 10 markets outside the U.S. is now around 7%. In meningitis, our portfolio achieved another year of double-digit growth with sales up 18%. Bexsero reach blockbuster status with sales up 23%, aided by CDC purchasing and positive recommendation in Germany. MENVEO grew 5%, impacted by comparison to stockpile replenishments in 2023. And in February, we anticipate U.S. FDA approval of our new pen development ABCWY vaccine, combining the antigenic components of Bexsero…

Thank you, Luke, and good morning, everyone. Next slide, please. Building on the comments made by Luke and David, this slide shows a significant growth contribution from specialty medicines. Having delivered more than 80% of the growth this year by building scale and momentum in our respiratory, immunology and oncology business as well as ongoing growth in our HIV portfolio. Next slide, please. Moving to the income statement for the full-year with growth rates stated at CER and ex-COVID. Sales increased 8% and core operating profit 13% despite a 6% headwind from the loss of Gardasil royalties. Within this, gross margin grew 80 basis points, benefiting from the positive mix from specialty medicines and the supply chain efficiencies. Despite incorporating £150 million charge to drive future supply chain productivity. SG&A increased 2% year-on-year, benefiting from our returns focused, disciplined approach to investments, supporting global market expansion for key assets, including Jemperli, Nucala, long-acting HIV, Arexvy and Shingrix as well as a one-off credit from the Zejula royalty dispute in quarter 1. R&D grew 7%, broadly in line with sales as we invested in Phase 3 trials, particularly in RI&I and oncology. Core EPS grew 12%, slightly below operating profit, as anticipated due to an expected increase in the core tax rate. And turning to the total results, operating profit decreased materially year-on-year to £4 billion. The reduction reflected a £1.8 billion charge relating to the resolution of the Zantac litigation and a higher CCL charge driven by the improved long-term outlook for our HIV business. Next slide, please. Core operating margin improved to 29.2% up 130 basis points year-on-year at CER and ex-COVID, notwithstanding the absorption of 140 basis points due to the loss of Gardasil royalties. This marked improvement demonstrates productivity, efficiency and optimized resource allocation to the key…

Thanks Julie. so in summary, GSK is powering forward. This comes on the back of a strong track record of operational delivery and accelerating progress in innovation and pipeline development where of course, there is always more to do. Our portfolio is demonstrating both growth and resilience built around high-quality specialty medicines and vaccines with more to come in key areas of therapeutic strength for GSK. As we head into 2025, we expect another year of profitable growth, and we have further improved our long-term outlook to sales of now more than £40 billion by 2031. Our outperformance and stronger balance sheet support our future investment plans, including for more investments in R&D, more business development as well as providing us with the opportunity to deliver enhanced shareholder returns. All of this underscores GSK's opportunity to deliver scale, health impact to patients through this decade and beyond. Combining science, technology, and the talent of our people to get ahead of disease together. Thank you very much, and I will now open up the call for Q&A with the team.

Okay. Thank you. For the Q&A portion of our call, please use the hand raise feature in Zoom webcast if you would like to ask a question and as a reminder, we ask that you limit yourself to only one to two questions so that we may accommodate as many participants as possible. For our first question, we will go to Emily Field from Barclays. Emily, can you please ask your question?

Hi, thanks for taking my questions. I'll ask two hopefully quick ones. Firstly, I know you mentioned impact from sort of the China macro on Shingrix. Obviously, with the Merck announcement yesterday on Gardasil, a lot of concern that this has the deterioration in this outlook has accelerated. So I was just wondering if you could provide a little bit more granularity on your expectations for Shingrix in China in 2025? And then secondly, within the mid-single-digit growth for HIV for 2025, are you assuming much of a competitive impact from the launch of lenacapavir in the second half of this year? Thank you.

Thanks. Well, we'll go to David a minute on HIV and our confidence there. And let's go to look first on China. I just would flag this is something that we addressed last year with the repositioning of our deal with our trusted partner Zhifei, and I think still remain ambitious, although the short-term pressures were acknowledged both through '24, and of course, in the guidance that we've given to '25, but none of that takes away from our longer-term ambition. Look Luke, do you want to comment a bit on China?

Sure. Thanks very much. Thanks, Emily. I mean, as Emma said, look, there's not much more to add than what I covered on the Q3 call. I mean our market share is around 70%, and that's our target population there. We're very happy with the partnership with Zhifei, but the intent to extend it out to 2034 is to -- was to address exactly what we're seeing right now, which is just to navigate the short-term headwind. Our focus operationally is partnering on the ground with Zhifei to expand in those high-tier cities and initial signs are encouraging. But again, I wouldn't expect too much in 2025. This is a mid- to longer-term play here.

Thanks. Hey, David.

Yes. Thanks, Emily. So firstly very pleased, obviously, with the continued strong growth momentum in HIV in Q4, contributing almost £2 billion of sales. I think on your specific question, look, we certainly expect Apretude to continue to grow this year. First and foremost, the PrEP market in the U.S. is actually significantly underdeveloped. The CDC estimates, I think about 1.2 million Americans could benefit from PrEP and stay only about a third of those are getting any form of PrEP treatment. We also know that the PrEP market is very well suited to long-acting options. And I think Apretude now the competitor product have very similar pipe strong efficacy, probably or definitely better than the orals, mainly due to compliance. So I think with the second long-acting entrant coming into the market this year, it should help grow the market for all of us. And then secondly, the competitive product definitely won't be for everyone. We now know that there's quite a high frequency of modules that people experience in their optimum where the two injections are given. I think in the pivotal study is about 63% of participants experiencing not deals with a mean duration of about six months and seven cases of ulceration. I expect we'll learn a lot more as the year goes on through more data and more real-world evidence of exactly what type of patients and the size of these nodules and so forth. But for potential PrEP users who are or body image conscious, which will be quite a proportion of them, I think that potentially is an issue. And then I would also flag that the competitive product has quite a high number of drug-drug interactions made 14 classes of commonly prescribed prescription medicines, corticosteroid, erectile dysfunction, meds and safe forth. And also DDIs are recreational and MSX drugs, opioid fentanyl and so forth, and these DDIs can be serious and in very extreme cases, potentially cause fatal respiratory depression. So again, for PrEP users or potential PrEP users who are taking these meds, it may not be for them. So we'll see how this unfolds, but I think we expect to grow in a growing market.

Thanks, David. And just to underpin, we welcome the opportunities to grow the market. But even if this market triples in size and we get to the 100% participation to the part of the market with the CDC said could be treatment is still where most of the businesses. And here, we obviously lead the way. So next question, please.

Great. The next question will be from Richard Parkes at BNPP Exane. Richard?

Hi, thanks for taking my questions. So I've got a couple of questions on vaccines and the targets. So on Arexvy, obviously, you saw a rapid penetration of the U.S. market, but there's still a large international opportunity. Can you discuss how prepared you are to access that in 2025 and what the key factors are in driving that or limiting your ability to access the opportunity. And then again on vaccines. Obviously, you talked about moderating expectations for Arexvy, Shingrix. Can you talk about what's assumed for peak sales of both those products now? Because I think the market is quite skeptical about your prior peak sales targets given the current headwinds? And just wondering what the offsets are to raising your 2031 targets? I know Blenrep obviously been included, but it sounds like there's some other offsets there where you're more optimistic. So helping understand those moving parts would be helpful. Thank you.

Yes, thanks, Richard. And I'll come to Luke to add a bit more color on how we see the opportunities for growth over time on Arexvy, because we really are in the foothills of this vaccine, which, as you know, we've really filled with the data that's come through on its efficacy and a high burden of disease area. Explicitly, there's no change to our ambitions for our assets, be that our existing ones or some exciting pipeline that's coming through later in the decade. The real question is actually the area under the curve. And obviously, last year, you saw us recalibrate our expectations in '24. We did say in Q3, we expected to recalibrate those -- or sorry, to maintain that the -- and acknowledge the short-term pressures on vaccines in '25, duly flagged then that we expected the mix to change has been more explicit today. We've been more explicit today on how that mix changes. And obviously, that has flowed through to our updated 2031 outlooks. Alongside, as you suggest, Richard, the impact of 13 positive Phase 3s, the momentum in our Specialty business more broadly. And as Julie said, we've upgraded whilst acknowledging the pressures on vaccines, we've upgraded our '26 outlooks for total specialty for HIV, also for Gen Meds, these have rolled through and we've added in Blenrep as I outlined in my introduction, this doesn't yet include our intent to invest in progressing the early-stage pipeline or our intent to pursue further BD like the kind of assets that you quite right at the beginning of January, IDRx isn't yet in that. So I think the key takeaway on this is the strength of our broader portfolio, the progress we're making in the broader pipeline means we can digest these what we think are short-term pressures in both the U.S. and in China, and we remain optimistic about our broader vaccines pipeline and lots more to come particularly in oncology and RI&I, be it Blenrep or ADCs or the other pipeline that's coming through. So with that, I think let's come back explicitly to Arexvy, Luke and how you see the international opportunity, whatever the weather in the U.S. is at the moment.

Sure. Thanks Emma, and thanks, Richard. I mean you know last year; we had about 15% of revenue was ex-U.S. I'm very encouraged by what we're seeing. It's early days, but we know what we're doing in this context. I think with these national immunization programs, which I said earlier, we've got six, that's in the U.K., Greece, the one in Czech, Saudi strong tender there, as well as critical success with STCO in Germany, in addition to the U.S., I think it's an encouraging start. I think what also is important as these systems will differentiate based on clinical data. And the market research that we have in these key markets is certainly very encouraging in terms of the perception of Arexvy, the efficacy of [indiscernible] groups as well as the durability and cost effectiveness of the vaccine. So I look forward to updating you more this year. But so far, it's a good start.

Thanks. Next question, please.

Great. The next question, we will go to Steve Scala from TD Cowen. Steve?

Hi, Steve, thanks for joining us early.

Asking Steve to unmute himself. All right. Steve will come back to you. And instead, let's go to Peter Welford at Jefferies. Peter?

Hi, thanks. Two questions. Firstly, just sticking with Arexvy at this time in the U.S. I wonder if you could talk a little bit about the commercial environment there, if you can. Because I guess in the last -- particularly in the last part of the season that we can see the prescription data for, it looks as though Pfizer is beginning to claw back quite a bit of share compared to what we've seen in the past. Can you just talk a little bit about contracting that you're seeing, I guess, for this year and perhaps also reluctance, I guess on that from pharmacies and buyers, I guess, to engage given what I imagine from their part must be pretty uncertain demand going into the next season, which I appreciate still months and months away. And then secondly, just on the buyback, I mean it clearly reflects your confidence in the longer-term pipeline that you already have, I'm guessing, internally relative to how the market perceives the R&D and what you have for new launches. So I guess could you talk a little about how -- I guess, how much of -- when we look at that chart, how much of it do you think is reflecting also things like long-acting HIV. And maybe you can put a number on how big do you think the HIV long-acting business could be beyond the sort of LOE expiries that we're seeing. And I guess trying to just sort of build some comments into what is it in the market is missing, do you think, in terms of the sort of resilience perhaps of the base business that gives you the confidence to do to allocate capital to a buyback today.

Yes. Well, lots of questions in that, Peter, I'll come back in a minute to Luke on the U.S. commercial environment in vaccines. Obviously, lots of external commentary and speculation on that for 2025, which also depends where we see the sort of pressured external environment, but Luke can add further comment on the commercial side. Look buyback is completely consistent with the capital allocation framework that we've laid out. And the first priority continues to be, as both Julie and I said, to invest in the future growth of the company to invest in the pipeline to invest it competitively and these exciting new launches that we've got coming through, be that the five approvals we hope to have this year or hopefully, as they progress, the 14 key assets that R&D with commercial partners working together on bringing forward. We also want to continue to supplement and plan to continue to supplement that with further business development. The point is that alongside that priority, we also continue to demonstrate our focus on improving shareholder returns. And obviously, considering the momentum in the business, the progress in the business, the strengthening of the balance sheet. We are very confident that we have both the circumstances and the opportunity to deliver really compelling returns to shareholders with this announcement that we've made today. Now I am not going to guide by individual product forecast in terms of what we will deliver in 2030. We've given, I think, a reasonable schematic that we've presented to you that showed most importantly. And this is really the key thing I think people should take away from today is our biggest business for it 19% in 2024 with every single therapy area growing at double-digits. It's still a nascent business, but the progress we're making in oncology is very exciting, and we have a potentially really material contribution to make. Even if the launch is staged. And it's really about the contribution to '26 to '31, certainly not to '25, but we're very excited about Blenrep coming through. And remember, that doesn't yet include first line, but we were pleased to start the study, let's see. But the data we have on overall survival is, we think, game changing as well as life changing. And so very excited to see what comes there and what could be added with ADCs and further progress we want to make. Explicitly on HIV, the six monthly drugs are not yet included in this outlook. So that's also worth bearing in mind. So I think that's where people should focus. No one should doubt for one second, not commitment to our vaccines portfolio, but really, it's the shift in the mix, which as Julie also said, secures the profitability of the business and the gross margin too. So with that, maybe, Luke, you can comment specifically on the commercial world in sales and revenue.

Yes. Thanks, Peter. Look, I mean, I think when I said -- came out with its surprising decision in June. I mean, we call a spade a spade and we said it was going to be tough. And I think the evidence has indicated that was correct. If you look at penetration rates in the U.S., the most recent data we have is in November, if we contrast that with December of 2023, I mean what ACIP signal has clearly happened, people follow ACIP. If you look at penetration, the 75-plus population at the end of '23, it's about 17% that only increased up to 26% over 2024. And if you look at high-risk individuals in the 60 to 74 population, it went from 11% to 18%. And in the generally healthy population where ACIP was steering people away, it just increased from 9.4% to around 14%. So there is a shift here in terms of demand. If we look at market research and profile, physicians still prefer Arexvy. But -- and I've said this a couple of times, for me, the key element here is to navigate what we think is going to be a transition from a three vaccine market to a two vaccine market. There is a huge amount of pressure, competitive pressure in the market through the contracting cycle last year. I think we've navigated that quite well. Our focus remains on retail. And what I would strongly stress is we need to compare apples with apples when we're talking market shares. So you need to adjust the market shares from internal volumes where we don't have the label. So if you do that, the end of 2024, we had about a 58% market share. So about 4.1 doses out of 7 million were with Arexvy. I think we're happy with that. The key thing is to preserve value and position ourselves for the future. When we do think ACIP ultimately will move to expand this population based on the evidence, there will be a revax at some point, and we want to be positioned to compete with Pfizer very actively at that point.

Thanks, Luke. And David, I think you want to add something on six monthly.

Yes, just on six monthly, Peter. I mean, as Emma said, it's not in our forecast, but I certainly agree with you that it could be a potential upside this year will actually be an important year for six monthly. We will have proof of concept data on 184 and also the two options that we could put with either 184 or one of the other entities. So N6LS the EMBRACE study at six months, I think we'll have a choroid and also our capsid. So the aim is to look at that data this year and then make a regimen selection for treatment and also choose our instate for PrEP next year and potentially run -- start running the pivotal studies in 2027. So as we go into next year in '27, that's probably the time when we think about formalizing the forecasts.

Thanks David. And let's remember, it was only four years ago, but we said we were expecting more than 33 billion in 2031. Today, it's more than 40 million. And you can see we're already close to that number in the near term. So yes, we are confident in our prospects. And yes, we know we've always got more to do. Next question, please.

Great. So let's go back to Steve Scala from TD Cowen. And Steve, see if you can ask a question now.

Thank you. That was my mistake. I have two questions. For Nucala, is the exacerbation data competitive with Dupixent and have you shown an FEV benefit, I mean, if not, your statements that you will lead in COPD might seem less secure. And secondly, you noted that GSK expects changes to U.S. vaccine policy. This contrasts with what another major vaccine company said just last week when they've reported, that company expects no changes. So in practical on the ground everyday terms, what exactly do you expect to happen and to which vaccines? Or is this more of kind of a big concern? Thank you.

Well, thanks, Steve. I'll come to Tony in a second on Nucala. The only point I would make is our ambition in COPD is across a portfolio of pipeline that Tony did share in December. So as well as Nucala, I'm sure who want to comment on that. Nucala is just the first foray for biologics for us there. And then in terms of changes to U.S., I think our point was we noted a significant speculation and let's face it. There's been a lot of it over the last few months around what kind of changes there might be to U.S. vaccine policy. And that is definitely one of the contributors to our view around the short-term pressures on the environment in the U.S. We also, as Luke reemphasize are still living with the decisions that were made by ACIP last year. And the key assumption is from us in that context is that there will be no further indications or cohort expansion assumed on Arexvy this year, although we do, over time expect them to be added and as Luke said, revax as well. I think the only point I would add without wishing to predict exactly what's going to happen is it was good to hear through the nomination process RFK reiterate is recognition of the value of vaccines. His own children have been vaccinated and also, obviously, over the weekend to hear that in the discussions with Senator Cassidy, the CDC vaccine guidance is -- and ACIP should remain unchanged. So let's see how this plays out, although we'll all know a lot more through 2025 and look forward to some of the speculation being settled here. Tony, do you want to?

Yes, let me start with, Steve, the first thing I'd say is that we're looking forward to being able to share that the total Nucala data set with you soon. I'm obviously not going to get into the details of that ahead of publication. But perhaps I make just stress a few aspects of this in particular in the context of exacerbations and the patient population. So if approved, Nucala is going to be the first monthly biologic proven to reduce exacerbations across the full spectrum of COP disease. And in particular, that includes individuals with emphysema who are the most difficult to treat. You'll recall from the data that we've previously published around the two prior Phase 3 studies across that population, an exacerbation reduction risk in the order of around about 20% is typical in the broader population. I'd also stress that we went to great lengths to ensure that we removed comorbid asthma patients from that study as well. And so I don't think it's difficult to compare side by side. However, we have a broader population, about a third of the COPD population of emphysema. And I'd like to ask just to comment on that. But one final thing, again, if you look back in our data similar populations and we've published some similar sort of headline efficacy on exacerbations, but it's important not to compare across headline data because it's a very different patient characteristics two studies.

Yes. Thanks, Steve. I mean Tony and I spent a lot of time talking about this. I think you just need to look at it practically on the ground. Tony mentioned about a third of those patients have emphysema alone, about a third of them have bronchitis, but also a third of them have mixed and can be difficult to separate those. So just practically, also, when you look at the Dupixent population and were not sick, they have a gold 2 to 3. So moderate to severe, whereas we were 2 to 4, which included very severe. And I think if you look at what the gold report, which just came out last year, said it's pretty much positioning Dupixent in that bronchitis subset. So again, I don't want to preempt our data, but I think we have a broader argument here. And also the important thing is to focus on hospitalizations because when people go into a hospital, obviously, many of them don't come out. And it sits off a cascade here. So in summary, we've got efficacy in tougher to treat patients, a broader population. And yes, let's see what the publication and the reception from the community says, but we intend to compete. There was a request for Dupixent for more competition, and we intend to provide it.

And this is what is great is the opportunity to grow biologics on the back of, by the way, are fantastic Trelegy business in COPD. And I am really excited to see what long-acting drugs are going to bring here. So good to see that we're going to be going into COPD study for [indiscernible]. We've also got the ILs and TSLP as well that Tony laid out. So I think this is the beginning of some exciting prospects and biologics that will get much stronger through the end of the decade, too in a disease that is the third leading cause of death. And so when you're talking about scale opportunities to address health and I feel that we really know what we're talking about, this is a good one. Next question, please.

Excellent. Next question is from Rajan Sharma from Goldman Sachs. Rajan, you are up.

Hi, thanks for taking my question. Just first one was on HIV. Could you just discuss the dynamics driving that positive impact from channel mix? Is that implying that there's a low proportion of Medicaid patients? And do you expect that to continue into '25 and '26. And then the second question is just on the 2031 guidance update. So you've taken up guidance by £2 billion in revenue, which includes Blenrep, which you've previously as £3 billion peak sales opportunity. So just to be clear, should we read that as kind of a £1 billion reduction in the guidance, excluding Blenrep or are you not expecting Blenrep to reach its peak into that. And then just related, there's obviously quite a bit of a difference between where consensus is right now. Is there anything particularly that you'd call out as where that delta is?

Yes, I mean Julie, you might want to comment in a minute on consensus as much as you wish to, and I'll come to David on HIV. But first of all, to be clear, the outlook for '31 is a more than £40 billion. And we're pleased to have moved that up, as I've said, which is a combination of rolling forward the mix shift in '26, progress in our Phase 3 results and across the portfolio and the inclusion of the Blenrep second-line launch as well. There is no change to our ambition for Blenrep to be more than £3 billion peak year sales. There was no time put on that, and we're looking forward to the contribution of the five approvals that we flagged and more to come, really contributing to that '26 to '31 outlook. So David, do you want to comment on the HIV?

Right. I think the main channel mix evolution we expect this year is just the ongoing rise of 343, which is somewhat of a headwind, but not huge. Other than that, I think it's going to be more of the same in the Medicaid and the related programs like Ryan White ADAP and so forth are about 40% of the U.S. HIV book of business. Medicare is about 20%. That is steadily increasing over time. Obviously, as patients get older, and the rest is private insurance. So very much apart from 340B, I think pretty much the same trends continuing.

Thanks. So Julia.

So in terms of the difference with consensus in terms of our outlook, which is more than £40 billion, the two main therapeutic areas where we've got a difference are oncology and respiratory immunology and inflammation. And within the oncology category, the two biggest ones are Blenrep. And obviously, people are probably waiting for the law and then also Jemperli. So we've got life cycle indication. And you've seen the track record we've got on Jemperli already with some important readouts coming up. So those are two big differences. And then within the respiratory immunology and inflammation area, we've got camlipixant, where obviously people are waiting for the readout that's coming in about a year. And then also depemokimab, interestingly, even though we've now got successful filing. Clearly, we've got the approval expected towards the end of the year and the launch at the beginning of '26. So those are the main areas of difference, which we have got with consensus.

Thanks, Julie. Let's remember, I think it's 72% of reductions in exacerbations that cause hospitalization on deep. So even if that's really a '26 launch totally with an approval at the end of this year, just considering the burden of disease, cost of hospitalization, the enthusiasm and Lou presented this research before from HCPs as well as patients for this that's definitely one to watch. Next question please?

Next question will be from Justin Smith at Bernstein. Justin?

Yes. Many, thanks indeed. It's just one on Blenrep. I'm sorry if this is a slightly ignorant question, but with regards to that DREAMM-10 Phase 3 first line, the MRD endpoint. Just could you share a few thoughts how that endpoint resonates with payers and community docs, particularly those outside the U.S.?

Let me just start with the dynamics and data plan associated with MRD and remind you of what we've already seen with molecular bases in DREAMM-7 and DREAMM-8 and then Luke perhaps I can hand over to you in terms of the resonance with key docs. So we were expecting. And again, a reminder that an ODAC approval of the use of MRD as an end point was only just last year or a recommendation of the use of MRD's endpoint. We started the studies Emma mentioned in December, we're expecting the first readout on MRD data in '27. What needs to occur over the intervening period and others will be driving this based on their own first-line studies is a relationship between an understanding of MRD and a more established regulatory endpoint like PFS. What we know from our own analysis in DREAMM-7, DREAMM-8 and indeed, other first-line service on Blenrep is when we look at the characteristic on details of the MRD readouts. And we see a similarly improved outcome for Blenrep relative to competitive assets. But Luke, you might want to comment on?

Yes. I mean, thanks, Justin. And just to build on Tony's point, I mean the market research we get is exactly what the FDA is signaling, which is MRD is a practical response to very long durations and clinical trial feasibility in first line. What it is not is a replacement for survival in second line. And I think that's absolutely critical, and we see that. So -- and as we've covered earlier, we've got very strong data in second line and look forward to talking more about it over the year.

Thanks, next question please.

Great. Next question will be from Graham Parry at Bank of America.

I have questions. So first question is just on the guide mix for 2025. So relative to consensus, it looks like the guide is a little bit worse than consensus is looking on vaccines, but Gen Med is better and stable. I think most were looking for a decline there. So could you give us some little bit more color behind the outlook on Gen Med, especially because I think there was some rebate adjustment benefits to Trelegy in 2Q last year. So you're actually looking for underlying growth. So what gives the confidence in that holding flat in the year and maybe the durability of that beyond 2025. And then secondly, on the buyback and free cash flow allocation, just perhaps give us a little bit of a sense of where you see free cash flow in 2025. If you're generating around £3 billion in '24, you're moving to a £2 billion share buyback and you -- but you highlighted low leverage. Are you now assuming you're going to increase leverage through the year as you see opportunistic -- to fund opportunistic BDL to make sure you're still funding the pipeline? Thank you.

Thanks, Graham. Well, two brief questions. But Julie, so over to you.

Thanks, Graham. So in terms of the RAR adjustment we had last year in the second quarter, it was largely, there was -- there's a high level, obviously, Trelegy was performing extremely well, and that attracts high levels of RAR. We had a true-up in the second quarter simply because when the claims were coming in, they were at a lower level than expected when the people were moving into the catastrophic coverage quicker, and that was causing that. Obviously, we don't know, but it was a benefit in the second quarter of last year. In terms of the leverage point, obviously, we've ended the year really well. We've got leverage of 1.2x net debt to EBITDA. We'd expect to run the buyback, as we've mentioned, over a period of within 18 months. Obviously, the weighting will be more towards 2025. So the leverage will move up during the course of the year. In terms of cash flow expectations, the '25, obviously, slightly below 2024. We've got the Zantac settlement going through, which is expected in the second quarter. And then we will have an upside from obviously, operating profit growth RAR likely and trade payables.

Okay, great. Next question, please. That's the last question.

Yes. So let's go with one final question from James Gordon. James, you are up?

Hello, thanks for taking the questions. Two quick ones, please. One was just capital allocation building on one of the earlier questions. So where is the ceiling in terms of how levered the company would now be? I think you'll now be about 1.6x, could you go much above that and so you could still do multibillion pipeline deals? Or is that optionality off the table really? That's the first question. And the second question is just coming [indiscernible] has mentioned. So I think we're going to get one of the Phase 3 end of this year and one early next year. But Merck's which is also P2X3, that had maybe similar efficacy to Phase 2 and obviously we didn't come to market. So what is the latest thinking and what you actually need to show in camlipixant. And how confident are you sorting to be a blockbuster product for GSK?

Thanks. Well, I'll come to Tony to answer on that and the two studies that we've got coming. And Luke, you might want to add also a reminder on why we wanted to do this deal and what the patient opportunity is. In terms of capital allocation and business development, I'm just going to repeat what we've said, which is our #1 priority is to invest in growth. We do want to do more BD. I'm really pleased with the discipline that has gone into the kind of business development that we've been doing, the bolt-ons in our core areas, some with that might be a risk but very high return and really nice tuck-ins, including the IDRx one that we just announced. You should expect, James, the kind of BD we've been doing at the kind of scale and pace and with the focus and with the discipline that we've been doing. Obviously, we want to underpin all of that capital allocation with a strong balance sheet. And Julie, I don't know if there's a sense as what you want to say on leverage, but...

No, I think in terms of the ceiling, you questioned about the ceiling. Obviously, we want to retain the strong investment-grade rating. Clearly, rating agency is getting a period of leeway with regard to that. So we're not going to set a number because it's not a scientific number, but we're basically very comfortable with where the balance sheet is. As Emma mentioned, very clear priorities about capital allocation. They haven't changed. It's just the robustness of the balance sheet that allows us to do the buyback complemented with what we're already doing in BD.

And all supported by the strong momentum in the delivery of the business, which we're running to maintain. So…

Camlipixant. And just quickly then, James, I think it's really important when you look at this area in P2X3, not just to think about efficacy, but in particular to think about therapeutic index, if you remember, camlipixant has a far improved therapeutic index, particularly with regards to taste disturbance. We have less than 6.5% adverse events in our study so far, compare that was Gefapixant, which had a nearly 70% taste disturbance. So it makes it hard to run a study when you're unblinding your treatment group. I think we have just to keep it short, a far superior asset on a clinical trial program, which has been designed to take account of the aspects of frequency of cough. And as I mentioned, we will not be unblinded functionally by the taste disturbance and the that Gefapixant was.

Luke?

Yes. I mean just to build on Tony's point, I mean, the smooth Phase 2b, we saw around 34% cough reduction, I think Tony's team is doing an excellent job in terms of execution of that study. Merck's molecule was basically validated the target that had floors in its selectivity and there were some challenges in study design around cough. These have all been incorporated into our program when we talk to pulmonologist, they still express high enthusiasm. The numbers are quite big. If we model out to 2030, we expect around just under 3 million patients in the U.S. will have had chronic cough for more than a year. And actually over that number in Europe. So we're talking large numbers of patients sitting in primary care and also pulmonologist respiratory physicians, offices and there are limited options for those people at this point.

They're really high dissatisfaction with current standard options. So thanks, everybody. Again, after a strong '24, we really are looking forward to another year of profitable growth and pipeline progress, and we're really pleased to be upgrading together our 2031 outlook again, with prospects of 50% of our business, by then more than 50% being in specialty medicines. And this continued performance and a stronger balance sheet are really underpinning our plans to continue to increase investment in the 14 key assets that we're focused on in the pipeline, in BD and in the successful launches ahead, and of course, staying focused on improving our direct returns to shareholders. With thanks to everyone. We look forward to catching up with you in coming days.