GSK plc

Good afternoon and welcome to this GSK Q2 results and accelerate growth event. Today we look forward to having a good event and if you could have the agenda slide on the screen please. Just a few words on logistics before I hand over to Luke. The first thing is that we have a Q&A session for you planned at 2.45 and another one then at 4.20. After the first Q&A, you will have a short break and the event is planned to end around 5 p.m. Next slide, please. Also note the legal disclaimer on our cautionary statement regarding forward-looking statements, and I would like to add that any definitions in terms of our reporting as well as assumptions on X-ray growth can be found at the end of this deck. Lastly, if we comment on performance, any of these comments will be made at constant currency or CER unless otherwise stated. And with this, I'm delighted to hand over to Luke.

Thank you.

Welcome everyone and thanks for investing your time here to join us in person at the London Stock Exchange and on the webcast. If anyone wants photos of the South Cambridge railway station, which is the lovely orange colour, Mick Reddy has them. So we can send them to you after. Seriously, today is in two parts. The first will give you an overview of our Q2 results. Then we'll move to what is the primary focus of today, which is GSK products and our plan to grow the business and how we'll create value for both patients and shareholders. So first I'll cover the results we announced today quickly. So Q2 performance was strong. We've got continued operational momentum. with sales up 5% to more than 8.4 billion pounds. Core operating profit grew 7% and core earnings per share were up 9%. Our cash generation remains very positive at 4.3 billion pounds and our Q2 dividend is 17 pence. And we're on track in terms of our responsible business rating. In July we also closed the acquisition of New Valence. Newvalent is a precision oncology company closely aligned to our approach to VD and I'm delighted to say that this acquisition has already contributed to our portfolio with the approval of J. Datra and pre-treated ROS1 positive non-small lung cancer just last week. Looking forward, we are updating our full year 2026 guidance with sales and operating profit now towards the upper half of the range. with EPS now expected in the lower half of the range following the acquisition of Newvalent. I'll now hand over to Nina who is going to summarise how we're delivering this growth and she'll also take you through some colour on Eucala and CoPD, Exentia and Blenrep.

Thank you Luke. Hi everyone. Commercial momentum continued in the second quarter, driven by key products across our specialty and vaccines portfolio. Growth was driven by specialty medicines, which grew 14%, and vaccines, which grew 8%. Vaccines growth benefited from the global expansion of Raxi, our RSV vaccine, strong performance from our meningitis vaccines, and Shingrix in Europe. Specifically, our expert benefited from a tender win for a two-year supply in Australia. Specialty growth was driven by Nucalla's continued COPD launch and our long-acting HIV treatment, Cavanuga, as well as Devato. General medicines was down 9% in the quarter, with declining sales of the older established portfolio. Also, there was a challenging pricing comparator for challenging the US due to a positive true-up that took place in the second quarter last year, also software inhaled respiratory market demand, both of which we expect to improve in the second half of this year. As Luke mentioned, we are focused on the products that drive the most value, including new launches and growth contributors. Next slide please. Here we have pulled out the three major launches of 2026. Starting with Nucala, we once again had strong global growth driven by the COPD launch and its halo effect on the other indications. In the U.S., new-to-brand prescriptions were up 69%, with COPD driving more than 70% of the growth. Internationally, sales were up 18%, primarily driven by our success in China, where Nucala gained majority share of bio-naive patients in COPD and already has MRDL lifting in severe asthma and nasal polyps. We are also continuing with the launch of Extenture, our twice yearly IL-5 for severe asthma. The J-code went live on July 1st, reducing the logistical burden on prescribers and providing certainty on reimbursement. We are continuing to build access and coverage with more than 50% of insured patients now being covered. The majority of new patients are coming from the bio-naive population which we expect will continue as around 70% of patients who could be on a biologic for severe asthma still are not. And finally, BlenDrop, our community-ready antibody drug conjugate for multiple myeloma is building in line with our expectations. We now have approval in 49 countries and recently we have gained reimbursement for Germany and Spain. In the UK, that's the country where Blendrip launched first, we are seeing a shift in second line treatment, as shown in this very nice chart provided directly by NICE, with Blendrip now leading in new patient starts. In the US, we are receiving positive feedback from physicians with strong intent to continue use. As we've said before, our approach is to go slow to ensure positive experience. helped by the J code, which is now in effect for BlendUp as well. As we enter the second half of the year, we will continue to focus on unlocking the community opportunity where the majority of the patients are. And with that, I will hand over to Deborah.

Thanks, Nina. I'm delighted to report another quarter of double digit sales growth at 10% Reflecting continued execution of our strategy and sustained market growth of our long-acting injectable portfolio, which in Q2 represented 80% of our total HIV growth. In the US, we accelerated our market share growth, continuing to outpace the competition with sales growing 14%. Long-acting injectables contributed 35% of sales, underscoring strong execution in a competitive market and increased demand for our HIV medicines. Cabinuva continued to convert patient preference into sustained growth with sales plus 33%. This performance was fuelled by patient demand and in the US, 77% of new prescriptions came from competitive products, reflecting increase in confidence among both healthcare providers and people living with HIV and the benefits of long-acting treatment. Aperture sales increased 39% supported by more than four years of real-world evidence and tolerability data. At age 2026, six-month follow-up clarity data further reinforced a more favourable injection experience. after a single dose of each drug with 70% of participants rating CAB as very or totally acceptable compared with 37% for Len. In addition, fewer HCPs reported challenges with administration and patient management. Given our continued growth momentum, we are raising our 2026 sales growth guidance to high single-digit growth from mid to high single-digit growth.

I'll now hand over to Julie.

Starting with the core income statement for the quarter with all commentary at CER. Sales grew 5% and growth margin improved 250 basis points due to product mix benefits driven by the growth of specialty and vaccines together with supply chain optimisation charges that we took in Q2 last year SG&A grew 5% driven by launch investments and phasing compared with the prior period partially offset by continued productivity gains R&D growth in double digits continues to be driven by accelerated investment in the pipeline, with three phase threes initiated across specialty in half one. And the royalties decline simply reflects the RSV IP settlement that we received last year. Operating profit grew 7% and EPS 9%, benefiting from a lower tax rate of 17.9% and the benefits of the share buyback. and then turning to the total P&L, results were impacted by the impairment of Kamla Pixant following the recent Calm 2 readout. Now turning to the first half cash flow, CGFO was 4.3 billion pounds, up half a billion versus last year, driven by operating profits, receivables and the CureVac settlement income. Free cash flow improved by a billion pounds with around half driven by the business and around half driven by one-off cash receipts relating to Linarex Abast and Veve. On the 15th of July, we completed the acquisition of Newvalent at a net cost of £7.1 billion, increasing net debt to £22 billion, just under two times net debt to 2025 core EBITDA. And the share buyback is now complete, with an average price of £16.13 over the 18 months. Now turning to guidance, I will now cover 2026 and at the end of the event I will cover the longer term outlooks. So following the strong start to the year we are pleased to be updating our sales and operating profit guidance towards the upper half of the range. Sales by product area has been modified with HIV and vaccines expectations improving to reflect the strong performance of Cabanova and also Shingrix respectively. Genmed is downgraded to reflect the tough environment together with generic competition. Operating profit reflects the underlying strong business performance and is now expected to be in the upper half of the range. with reduced SG&A and improved royalties partially offset by increased R&D investments. EPS is now expected to be in the lower half of the range and this is predominantly due to the additional interest of around 160 million following the acquisition of Newvalent. Now to support your modelling with respect to phasing, we expect operating profit growth to be significantly Q4 weighted. and a number of factors lead to this including productivity charges taken in Q4 last year whilst Q3 is impacted by the consolidation and saving of new valent costs and the acquisition related interest together with a tough tax comparator. Thanks and with that I will hand back to Luke.

Thanks Julie. Right, so coming back to the agenda, we'll now move to the accelerate portion of our event. As a reminder, we have allocated time for your questions halfway through and then again at the end of the presentations. Now, at the start I mentioned before that the focus of today is about products and growth and we'd now like to take you through our plan to do this. First we'll give you more details on our products and why we're confident in our ability to grow the business and then second we're going to update you on how our late stage pipeline is evolving. We're also going to talk about what we're doing to accelerate and expand our key late stage assets as well as working hard to improve our ability to find and develop new competitive products. And then finally we'll update you on how we're funding all of this. and essentially we will be reallocating capital and resources in a disciplined way to focus on what creates value. Hopefully at the end you'll have the same confidence that the team and I have in our plan and our ability to execute it. Next slide please. So what do we think our business is going to look like over time? Over the last few years we have delivered considerable strong growth with commercial execution and we will work very hard to maintain that growth in the near term while we invest in the late stage pipeline. In the mid term, we've identified key growth drivers. We think those growth drivers will compensate for the loss of dollar tergivere exclusivity and allow us to push through this transition period that I'm talking about. In the longer term, the changes we're making now to how we operate will accelerate the next wave of products to continue delivering top-line growth. And finally we remain very reactive in terms of BD and here we're looking for incremental growth opportunities that make strategic sense for GSK. Next slide please. So the biopharma business, our biopharma business has changed over the last 10 years. Here you can see that operational execution has driven the move from being a company that was highly reliant on a genericising base business of largely primary care products and commoditised vaccines to a growth orientated company with a broad mix of innovative products. And if we look at where we aim to be in 2031 and beyond, on the right hand side of this slide, GSK will continue to evolve to be more specialty focused. and that means a much larger proportion of our sales coming from oncology, respiratory and hepatology supported by a differentiated long-acting HIV portfolio. Now right now our portfolio is built around five core therapy areas so today our team will engage with you about the promising potential we see in each of these areas and these are the five areas we're investing in. This is where we're focused and whether they're walking into a lab, a manufacturing site, one of our offices or meeting our customers, every single one of our people needs to know how their role helps us deliver on these five priority areas. Because in our business, and certainly with this audience you'll understand this, a company's valuation is based on products and the core ability of management to recognise and deliver competitive innovation. and to do that senior managers have got to be close to the products and the people leading the project teams. So we've taken material steps with the late stage portfolio BD and advancing our early stage to ensure that we are evolving to do just that. Now I'll cover the mid and early parts of this slide shortly but starting with the late stage on the top left hand side. Every two weeks a subset of the executive committee, so Tony and Nina as well as Regis. Regis, are you there? I don't think many people know you Regis so that's Regis there. And Mondaire who everyone knows, Mondaire Maggiore who everyone knows who's on holidays right now. So we need to look at the progress of our late stage portfolio and selected assets every two weeks. These meetings are led by the product teams, the people running the projects and this allows us to delay the organisation and it promotes accountability. and the aim is to keep us all on top of the internal but also critically the external factors that influence our success. Now since these reviews were started in January we have identified acceleration opportunities across seven assets, 18 indications and 25 studies and you'll learn more about all of this today. Now as a result of these efforts by our team we have over 20 Thank you very much. Thank you. as part of the strategic portfolio of reviewing process and in order to give us the confidence to invest right now. This is a busy slide but I love it. I think this slide does a good job of showing you how these elements come together in terms of the late stage portfolio, the momentum that we have and the bolus that we've built up in phase three starts. There will be attrition after we are talking about drug development. but that's why we have a broad portfolio and our portfolio really is a set of assets that we are confident that is competitive and that can drive growth. For the mid-stage portfolio we will continue to supplement our pipeline with business development and we'll focus on products that address a validated target and where there is an efficacy or tolerability gap. So far this year, we have executed three deals. Looking at this list, we missed with Bellis and Camlipixen in cough, but we've just got approval with Gydatro in lung, and overall, the majority of assets we've acquired with these deals have progressed to phase three. Next slide, please. In the early stage, we need to improve our output, and we've got to keep evolving how we work and who we work with. I mean this slide shows we're putting our money where our mouth is. This is why we're closing Stevenage and moving our people up to Cambridge. I mean having lived in Cambridge and worked at one of the places listed up there, I know the power of relocating to this environment and it is designed to help Tony and his team drive change and to make us fundamentally better at discovering and developing new drugs and Tony is going to take you through this in depth shortly. So how are we making all of this happen and how are we paying for it? To realise the opportunities in the late stage portfolio and R&D, we have announced today an Accelerate Growth Program. This program is about relocation allocation within our existing P&L to fund these studies and labs. This is a three-year program that will enable us to increase investment in R&D by targeting annual cost savings of 1.9 billion pounds by 2029. To do that we will incur an expected one-time cost of 2.4 billion pounds which will be 2.1 billion in cash. The majority of these savings we were making will be reallocated to the late stage pipeline and some of that money will also go towards strengthening the margin through the dollar tag review loss of exclusivity period between 2028 and 30. Now this is fundamental to our strategy. We plan to evolve the company's cost base in line with its shifting product portfolio and to accelerate, to deliver accelerated long-term growth and value to both patients and our shareholders. Next slide, thanks. Finally, this is how we see the late stage portfolio. As you can see, the portfolio will evolve over time, accelerating growth to drive long-term value for patients and shareholders. Now with that let's get into the nuts and bolts of how we're going to make this happen as a team and to get that started it gives me an enormous pleasure to hand over to Tony.

Hi everyone, delighted to be here with you and thanks Luke. As Luke highlighted earlier accelerating R&D is a key priority for us and this means focusing on three important areas. maximizing the value of the late stage portfolio, supplementing our portfolio through business development, and of course, accelerating the progress we've been making in changing the way we work in R&D. I'm pleased with the progress we've already made. Starting on the left hand side of this slide, you can see the value of our pipeline is increasing. In fact, we've more than doubled the number of phase two and phase three assets with blockbuster potential since 2022. Our pipeline is also moving 25% faster, meaning we're now in the upper quartile of our peers based on recent CMR benchmarks. We expect this trend to continue to improve. Together this means we can do more, and as you can see, we significantly increased the number of phase 3 starts this year compared to the past. 2026 will be a boldest year for phase 3 starts based on our acceleration decisions, which I'll cover in more detail in a moment. Much of this has been achieved through our use of data and technology. It enables faster decision-making with greater confidence, something we continue to embed in all aspects of R&D. As Luke mentioned, we're taking a new approach to reviewing the portfolio. And this means experts from project teams present directly to myself, Luke, and Nina so we can make quick decisions, resolve issues promptly, and provide support to advance exciting programs. The approach ensures we have the right alignment across R&D, commercial, and medical to make the most informed decisions possible. It's fully cross-functional, data-driven, and has already allowed us to confidently make a number of acceleration decisions, which you can see on the right-hand side of this slide. These are the assets and programs you'll be hearing more about today, so you can understand why we're excited about them based on their differentiation and potential benefits to patients. In oncology, our ADC portfolio has been significantly accelerated. This is supported by data from our partner, Hanso, as well as our own global clinical program. Our decision to accelerate five phase three studies from low res in gynecological tumors and four for res res in lung and prostate cancer demonstrate our confidence in these assets. In respiratory, we'll start six phase three trials across indications for our ultra-long-acting piece of GSK283. This is a significant acceleration of its development path. KVAN will describe emerging data which support the use of the six-monthly regimen for treatment of diseases like COPD. For as thin as Furman, data suggests a best-in-class profile for the treatment of MASH. The program has recently been accelerated against our original timelines and now includes F4 in addition to F2 and F3 patients. and I'm pleased to announce that the F4 program recruited its first patient only last week. As you can see on this slide, the changes we've been making in R&D, particularly in development, have led to a transformation in our late-stage portfolio which is now much more focused in areas with greater patient benefit and value. Overall, we're significantly increasing the number of Phase 3 starts significantly this year. We expect this trend to continue to be above that of the past, although not at the level we're seeing at this year. Importantly, these are in high-value areas, with the major driver of this being a significant increase in the number of oncology phase 3 studies. In 2026, we'll see the start of pivotal trials for Mores in gynecological cancers, Rizrez in genitourinary cancers, Valsatinib in first-line GIST, Afinisfermin in F4 mash, and our three times daily treatment for HIV. External innovation and business development have been and will continue to be an important part of accelerating R&D. Luke's highlighted the deals we've added important assets to our late-stage pipeline, most recently, of course, Newvalent. We'll continue our approach of bringing in assets with validated targets that address efficacy or tolerability gaps to complement our mid-stage pipeline. We use the same data-driven, scientifically courageous approach I just described for our BD decisions as well. It's true for both clinical and earlier platform deals, and in the latter case means R&D is increasingly externally focused. You'll hear more from me on the early stage R&D later in the year. Now as we become more externally focused, we're also making sure we co-locate our key laboratories with major external innovation hubs, We have four key locations, the east coast of the US, UK, Europe and China, each with important academic partnerships, and I've highlighted the major ones on this slide. The partnerships span a portfolio of interests aligned to our core therapeutic areas and forge deep connections with leading researchers that expose us to groundbreaking innovations. The majority of these projects focus on human health data, giving us unique insights to de-risk our target identification and translational efforts and allow us to advance faster with greater confidence. We continue to actively look to expand our partnerships on the east coast of America and in China and I look forward to sharing updates with you in the future. In Europe we already have a significant presence with very strong partnerships like the one we have with Oxford University. The announcement today that we're establishing a hub in Cambridge, UK shows our commitment to ensuring our people are in the right places with the right partners to accelerate innovation. Our new Cambridge site will accelerate the changes we're making within R&D, reflecting the new way of working we've built to discover and develop medicines. CBC is one of the leading integrated biomedical campuses in the world and as such is a perfect location for us. We'll be beside one of our key academic partners, Cambridge University, as well as with internationally recognised research hospitals and clinical infrastructure. Our scientists will be able to work in state-of-the-art technology-enabled labs with an ecosystem of innovative AI and biotech companies. This move is part of a broader transformation of R&D, which I'll continue to update you on. Finally I want to reiterate the strength of our late stage portfolio which has been delivered from the momentum we've been building over the past years through business development and most recently our acceleration decisions. We have a number of exciting milestones ahead of us and I look forward to updating you on these in the future. With that in mind, I'm now going to hand over to the team to take you through these programs in more detail, and we're starting with Hesham and our oncology portfolio.

Thank you, Tony, and good afternoon, everyone. I'm Hesham Abdullah, Global Head of Oncology R&D at GSK. Today I'll highlight the significant progress we've made in oncology, building on our strength in gynecological and hematological cancers, and expanding into new tumor types. Given the additional R&D investment we're announcing today, I'll also discuss how we'll focus this investment to accelerate development and bring our pipeline of clinically meaningful medicines to patients faster. Let's start with why oncology matters. Thank you for joining us today. There remains a substantial opportunity to improve patient outcomes. Our pipeline and team are well positioned to address this growing unmet need. We built a portfolio of competitive, high potential assets and critically, we have a talented team with a proven track record of execution in oncology. This combination of high unmet need, a high potential portfolio, and a proven team will make oncology a key growth driver for GSK. We've been deliberate with how we've rebuilt the oncology pipeline at GSK, starting with strong franchises in hematology and gynecologic malignancies and now expanding into lung cancer propelled by their recent new valent acquisition, as well as gastrointestinal, prostate cancer and other solid tumors. Building on our marketed anchor assets, We're advancing a deep clinical stage pipeline across multiple modalities, including ADCs, next generation targeted small molecules, immune cell engagers, and novel precision oncology medicines. We're focusing on developing a better understanding of cancer biology, generating unique insights from deep phenotyping, novel non-clinical model systems, and foundational models for patient identification and stratification. These differentiated oncology technologies enable sustained growth and innovation with a quality portfolio of assets in our research pipeline. End to end, our GSK oncology portfolio is designed for scale and sustained leadership. Turning first to our two lead antibody drug conjugates, MORES and RISRES. Both ADCs utilize a proprietary topo1 payload with a proven linker technology designed to deliver enhanced stability and tumor penetration with a potentially differentiated safety profile. For example, in our B-HOLD intern study results presented at SGO, we observed a 3% incidence of IL-D pneumonitis. And we'll share further evidence of these potentially differentiated outcomes at ESMO with RIS-RES. We've already advanced both ADCs into pivotal programs Based on an extensive range of clinical data spanning across ovarian, endometrial, small cell and prostate cancer with data generation ongoing across other solid tumors. Early access to extensive Hanso clinical data sets in large patient populations combined with competitor insights and our own data in global populations allows us to rapidly incorporate learnings, design competitive phase three trials, and optimize our strategic positioning. At the same time, we're evaluating novel biomarkers to potentially further enhance activity with a multi-pronged translational strategy. Across both programs, we're delivering at pace, striving for flawless execution, while making smart, disciplined choices along the way. Most certified resi-tcan, or as we call it, mores, builds on the strong foundation of Sejula and Jim Purley to drive GSK's next wave of innovation in gynecologic cancers. Strong clinical data in both ovarian and endometrial cancer positioned MORES in the top tier of a competitive and emerging class of antibodies or conjugates in gynecologic malignancies. MORES delivered numerically higher anti-tumor activity combined with manageable safety with a 62% response rate in platinum-resistant ovarian cancer and a 67% response rate in second-line plus endometrial cancer. Importantly, This activity is independent of B7H4 expression level with no unique toxicities. For example, none of the trope two specific stomatitis. Supported by an extensive data set, we've moved at pace to initiate a scaled phase three development program, initiating five phase three studies during 2026, including three ovarian and two endometrial cancer studies. Driven by a strong signal observed with MORES in early clinical trials, the B-HOLD clinical program has recruited over 600 patients, and it has taken just 15 months to move from phase 1b to initiating phase 3. Expect further safety and efficacy data updates from MORES at ESMO. The second asset from this class-leading ADC platform is RISRES, our B73 ADC, which is effectively an oncology pipeline in a single asset. B7H3 is widely expressed across a large number of solid tumors. Across these potential indications, we're prioritizing early entry into small cell lung cancer and prostate cancer where proof of concept has already been established. In parallel, signal confirmation in a global population is underway in non-small cell lung cancer and sarcoma. Now that PLC has been established in China, and we're also exploring additional opportunities across multiple other solid tumors. With already more than 930 patients dosed across in bold trials globally, we have established a strong foundation to further accelerate RIS res development and maximize its potential. Similar to MoRes, robust early clinical data provides conviction to move our RIS-RES program with pace and at scale. In the second line small cell lung cancer setting, FDA granted RIS-RES breakthrough therapy designation based on the initial data presented by HANSO at the World Conference on Lung Cancer in 2024. The updated data published in Cancer Cell this year showed an objective response rate of 60% with a 6.3-month median progression-free survival and a 14.9-month median overall survival in the TOPO-1 naive cohort. Earlier in July, our partner Hanzo announced that ORDINUS-008, a Phase III China study, met its primary endpoint, demonstrating a clinically meaningful and statistically significant improvement in overall survival for patients with second line small cell lung cancer. This marks a significant milestone as the first positive phase three overall survival data for a B73 directed ADC in any tumor type. Our global GSK phase three study in second line plus in both small cell lung cancer 301 is actively recruiting and we plan to initiate a first line study later this year. In a China non-squamous, non-small cell lung cancer second line plus population, RIS-RES has demonstrated meaningful activity, both as a monotherapy and in combination with a PD-L1 inhibitor. Our ongoing phase two combo study in BOLD-PAN tumor 101 will aim to confirm this signal in PD-L1 exposed patients in a global population. Prostate cancer is a key growth opportunity for RIS-RES. and we will initiate a number of Phase III studies in prostate cancer before the end of the year. The EMBOLD program includes two Phase III monotherapy studies in late-line and chemo-naive metastatic, prostate-resistant prostate cancer, as well as a Phase III combination study in metastatic, hormone-sensitive prostate cancer. These accelerated investments are supported by the response data shown here on the left A 37% confirms objective response rate in metastatic castrate-resistant prostate cancer patients, supported by 9 months landmark PFS rate of 56%. WISRES is complemented by a growing pipeline of early-stage prostate assets that position us for future expansion with different modalities. Highlights for the remainder of 2026 include the Artemis 008 data set which looked at res res in second line treatment of small cell lung cancer. This trial met the overall survival primary endpoints and data will be published before the end of the year. These data are significant because this is the first pivotal trial to show a survival benefit for any B7H3 directed ADC in any indication. In addition, Our partner Hanso has just announced positive results from a second China Phase III study evaluating RIS-RES in osteosarcoma patients that have received at least two prior lines of therapy. The trial demonstrated a clinically meaningful and statistically significant improvement in its primary endpoint, IRC-assessed PFS, with consistent benefit observed in key secondary endpoints. Osteosarcoma is an area of high unmet need. and RIS-RES has secured breakthrough therapy designation from FDA in this tumor type. Data from the phase three study will be presented at a scientific congress later this year. Additionally, at ESMO, we'll share the first RIS-RES data from a global population alongside ILD analyses that will further characterize the assets potential differentiated monotherapy safety profile. This momentum is expected to continue into 2027 with RISRES data being presented at major medical congresses throughout the year. Together, this represents a rich multi-year data cadence across one of the broadest B73 development programs. Turning to our recent NewValent acquisition, which provides access and precision oncology lung cancer. Now, Adelkib and Gyditro have the potential to transform treatment in ALK positive and ROS1 positive non-small cell lung cancer. The potential to improve efficacy and tolerability in ALK positive and ROS1 positive patient segments will support extended treatment duration and in turn, drive market growth. The ALK and ROS segments of the non-small cell lung cancer market represent around 2-4% of the overall population. But these segments are typically younger, they are more frequently women, and fitter than the broader lung cancer population. Patients are usually diagnosed with metastatic disease and typically have a higher rate of CNS involvement at diagnosis. For patients with ALK-RAS non-small cell lung cancer, next generation agents like Gyditro and Neldalkiv may extend median PFS beyond 46 months in RAS1 positive patients, and over 84 months in ALK positive non-small cell lung cancer patients. While the majority of first-line lung cancer patients will be treated for around nine to 10 months, the duration of therapy for a first-line ALK patient may be greater than seven years. Gyditro was recently approved by FDA for the second-line treatment across one positive non-small cell lung cancer patients. We're also working with FDA to support Nelodalkib approval with an FDA decision for second-line ALK-positive non-small cell lung cancer expected by November 27th. First-line studies for both Dridytro and Nelodalkib are still ongoing and enrollment in Nelodalkib's first-line Alkazar phase 3 trial is already more than 30% complete. In the cross-trial comparison shown here for Oc-positive non-small cell lung cancer post-second generation TKI, meledalkib shows 14.5 months median PFS compared with 6.6 months achieved with loralatinib, with 91% of patients maintaining a response for more than 12 months versus 70% with loralatinib in a TKI-naive population. In ROS1-positive non-small cell lung cancer post-DKI, Gyditro shows 23.8 months medium PFS compared with 9.7 months for teletrectinib with 96% of patients maintaining a response for more than 12 months versus 74% for teletrectinib in a TKI-naive population. Acknowledging the caveats that exist with these cross-study comparisons, these data appear to suggest the potential to meaningfully prolong median PFS with Nela and Gigitra. These are best-in-class efficacy profiles, and I will review safety and tolerability data on the next slide. Data from the NELCIP clinical program indicate Nela is well tolerated. with the lowest rates of dose reductions and discontinuation when compared with other assets in the class. Nela is a highly selective ALK inhibitor, which is reflected in the adverse event profile observed in clinical studies. Nela does not appear to be associated with the long-term metabolic and neurological adverse events seen with other TKIs in the class. While Neladelcib does show higher liver enzyme elevations, physicians' feedback indicates these are largely clinically asymptomatic and manageable with routine monitoring. In short, a tolerability profile designed for long-term first-line use. Bosatinib is another asset in our precision targeted therapy portfolio. It's in phase three development for the treatment of GIST or gastrointestinal stromal tumors, a rare type of cancer which develops in the digestive tract, most commonly in the stomach or small intestine. The first-line standard of care for GIST patients has not changed since the introduction of imatinib over 20 years ago. While this first-line therapy has improved the outlook for patients over time, GIST tumors will ultimately become resistant to imatinib and patients typically progress to a second-line treatment strategy. The standard of care in second-line treatment is not well tolerated with variable efficacy. Bilzatinib is the only agent in the TKI landscape which targets all primary and key secondary kidney patients. were the lower rate of adverse events when compared to other available treatment options or standard of care. At ASCO this year, we presented Valsatinib data, which showed a 61% confirmed response rate and a 65% unconfirmed response rate for Valsatinib in the first line setting, with every patient on the trial demonstrating a reduction in tumor volume. These data were used to inform the STRATEGIST frontline study, which recently started recruitment. We now have two phase three studies underway, STRATEGIST III and second-line GIST, and STRATEGIST frontline and first-line GIST, both exploring Valsatinib as monotherapy. Recruitment for both studies is progressing strongly ahead of schedule. This momentum underscores the pace at which we're advancing this asset and those at-nets potential to redefine the standard of care in GIST. Finally, I'd like to provide a short update on Blenrep, our ADC for the treatment of multiple myeloma. Blenrep's clinical development program is targeting all patient segments of newly diagnosed multiple myeloma. The DREAM-10 study is designed to investigate a Blenrep combination which is appropriate for the majority of first-line or newly diagnosed patients. These patients are described as either standard-risk fit or high-risk frail patients. DREAM-10 investigates a Blenrep triplet versus a Daratumumab triplet, and we anticipate preliminary MRD negativity data in the first half of 2028. For high-risk, non-frail, newly diagnosed patients, the Phase III Precox study will investigate a quad regimen of Blenrep plus VRD versus ACD38 uh a combination of daratumumab plus vrd in a high risk enriched population addressing the need for deeper myeloma control through higher treatment intensity together these two pivotal studies should support blend rep use in a large proportion of the first line multiple myeloma patients blend reps projected median progression free survival of Blenrep's projected median progression fee survival of 101.8 months from the Turpose data presented at EMN is competitive versus 100 months for a CD38 quadruplet regimen and 62 months from a CD38 triplet. Next, real-life burden of care. BRD offers a meaningfully lower burden of care with dramatically fewer infusion days. This has real-world implications for patients. And then finally, The grade 3-4 ocular event rate is significantly improved and matches first-line expectations. This is achieved with 1.9 mg per kg dosing on a once every 12-week dosing schedule in the maintenance setting. This is a regimen designed to optimize benefit-risk in this newly diagnosed patient population. Now, let me close with the big picture. Our GSK pipeline and team are well-positioned to address the growing unmet needs in oncology. We have a highly competitive oncology pipeline and we're continuing to apply various acceleration levers. Starting in lung, we have a near-term acceleration opportunity into second line with Jydetro now approved and Nela on its heels with first line expansion for Jydetro planned in first half 2027. Both address clear efficacy and tolerability gaps. With our two ADCs, extensive clinical data sets provide conviction to progress multiple pivotal programs at pace, with MORES and GYNONC and RIS-RES a pipeline in a single asset. RIS-RES brings the first positive phase three OS data for any B73 directed ADC, with two positive phase three trials to be presented in the second half of 26. Continuing with our pipeline of differentiated precision oncology medicines in areas of unmet need, Bosatinib has the potential to redefine a two-decade-old standard of care for just patients as a well-tolerated monotherapy with potential superior activity and tolerability profile. Finally, we will continue to see upside with Blenrep. The ongoing clinical development and evidence generation program aims to ensure success in newly diagnosed patients while creating broad access for community-based BCMA therapy. Taken together, this is a high potential competitive oncology pipeline and one we're advancing with real pace and conviction. I'll now hand it back to Luke to commence the Q&A session. If I can also ask Julie, Nina, Deborah, and Tony to join me on the stage as well today.

Thanks Hesham, and as you said, we'll open the floor to microphones, so please raise your hand, you guys clearly know what you're doing, and we'll get a microphone to you. If you are listening online and would like to ask a question, please raise the hand function and we'll get to you shortly. So, Matthew, I think you were the first. You get a job as a Formula One driver with those reflexes. So Matthew.

Thank you. It's Matthew Weston from UBS. One question really about, and it's about the financials before we get into all the detail, because there's more time to dig into the detail later. Slide 24, you gave the illustrative picture of the impact of the new 1.9 billion savings program. and it showed the cost base today and it showed a smaller cost base in the future and I think you're on track to deliver about 31% margin based on guidance in 26. So one of the most significant questions I've received today over and over is does the new cost saving take that margin target higher? So am I right in interpreting slide 24 that yes, you are now aiming for margins up at the end of the 2031 period relative to where we are today?

The position in the slide that was shared was basically saying it was the cost base as a percentage of sales, first of all as a result of accelerated growth. We are guiding to more than 31% margin in 2026. and what we've said previously before today was that the margin will be stable through dollar tag revere LOE which is 28 to 30 and we feel confident of that because the portfolio is pivoting more and more towards specialty number one and as you've seen over a number of years now and with this program we are driving productivity and improvement in the business so that brings us to date now what we've said is as a result of accelerate growth We will also drop some of those savings through to the margin in the period of dollar tegravir. So it builds in the dollar tegravir LOE period 28 to 30. We've not given a specific percentage, but what we have done is changed the margin guidance through dollar tegravir now to say it will be stable to improving. So we're giving a range and recognizing the drop through from the accelerate growth program.

I think Louisa, you were next, right?

Thank you very much. Louisa Hector from Barenburg. I wanted to check on the asset accelerations. So you've highlighted seven. What are the criteria for accelerating? Is there some new decision making in that mix? And then what I don't think NELA is an accelerated asset. Is there a reason for that? Maybe it's in flight, too recent. And if I can also ask on probabilities of success and linking that to the validated targets. So you have this awesome selection now of pipelines. Is there a reason for probability of success being higher with the 25 phase 3 starts? You talk about the validated targets. I don't know if How much of those, what percentage of those are with some validated targets and what that really means, a validated target?

Thank you. Thanks, Louisa. I'll start and then I think this is very much going to be a bit of a tag team answer. So maybe a little bit of heritage, a little bit of background. I mean, you're available in there because it was running on a similar track with the deal and the programs are more advanced. But if we can go faster... will certainly look to do that, but essentially we wanted to sit down and look at the portfolio, benchmark it versus external parameters, not just marking our own homework, but if you look at a classical program in Lung, what are the appropriate timeframes, what's a typical white space that's a fair comparator, and then what could we do to compress that, obviously applying common sense that we didn't want to go so fast that we increased risk. The other thing is, of course, as this portfolio is evolving, if you do have Thank you very much. and really compressing all of those and each program had different combinations and then we ended up, we ran up against Julie who said that's lovely and she's doing her job, she said this needs to be paid for and that's what then triggered the second round of the process which is to say okay well then how do we effectively use our shareholders money appropriately to try and unlock that and clearly moving it from historical areas of the business or areas where frankly we could partner or we could do things more simply and moving those monies to phase three programs and to BD, we felt it's a better return and a better use of our shareholder's money. So that's the high level. So I don't know, Tony, if you wanted to go to the column Nina and then Julie, just sort of how that flows through. But clearly, you know, at the end of the day, it's a benefit of a combination of benefit risk that we're looking at with these programs, classic portfolio management.

Tony, why don't I just start a little bit with what data underpins confidence. You're going to hear a lot more about that from Kayvan for example and you already did from Hesham and so I think you start with the fact that our portfolio now has a significant number of assets that have broad potential associated with them and what we've been doing and by that I mean a number of potential indications that carry significant value as well and we've been integrating data from a one-end human causal data from genetics all the way through clinical characterization of patients to individually detailed molecular data and what that allows us to do is if you like draw lines of confidence in underlying biology across different indications so that's one aspect of it You'll hear some nice examples from Kayvan after the break on that. Couple that then with the opportunity to be able to execute a clinical study in both an effective and, shall we say, appropriately dated way when we're going with relatively strong data as I've just described, but that's the absence of a phase two and what you have is a set of ingredients that allow us to then Thank you Dominic. Not much to add but Louisa to your point about the confidence

you know, I'll use some examples you know, those acting it we have seen, we have ongoing second line study, right when you see a study recruiting at 200% rate, that gives you a bit of confidence that there is actually genuine interest and desire to use the program, to use the asset and then we try to accelerate obviously starting first line and support to make it possible to hopefully repeat the same, I'm not promising it, but there is high confidence that that study will recruit. Other examples are the two ADCs. We have this massive benefit of having a Chinese partner who generate huge amounts of data very quickly. We are all aware that sometimes data generated in specification population might not be repeated, So the question here is which level of confidence we need to have in the global Western population to then embark very quickly into a phase three study. And for some of these we feel very confident already. So I think it's based, to what Tony said, it's underpinned by data, definitely. And also, you can imagine that we have, you know, we ask the teams to come bottom up with proposals. If you have blue sky scenario, what would you bring as acceleration? We had more than 100 opportunities that were brought by various teams. And We obviously looked at how big are certain opportunities and what does it mean for our 2030, what does it mean for post-2030 growth. And I think we are very confident that this point, our kind of cutoff is blockbuster indication. So that plays a role as well, together with how much does it cost, operational execution, is it feasible to do it and so on.

And just to stress something Luke said right at the beginning, we keep a very close eye on what's going on competitively. Particularly, for example, Kevin, I'm sorry if I get ahead of you, but T-Switch is a nice example. We got a hint that our friends at Generate Bio were getting ahead of us, which we didn't like the idea of. So that was something that went very quickly through this process, and you'll hear more about our program later.

and I think, again, we want to build a culture that's obsessed with products. Graham.

Great, thanks. It's Graham Park in the city. On the accelerating growth post-2031, can you just help us understand what you're assuming for cabotegravir IP protection there? So you've talked about protecting through dolotegravir, but the cabotegravir LOE is 2031. It would be pretty major if you actually lost it there, so you can detail how you're expecting to protect that. and then secondly on zidazantinib, what's your confidence in the ability to get approval on the first line data given I think it's only a 35 patient cohort and you've already got talotrectinib approved from Trust 1 to which actually had more patients and have you had any discussions with regulators regarding the filing yet?

Great, thanks Frank. Deborah, do you want to give colour on that and then raise us If you could just step through the process of making cabotegravir, because I think that's, it's quite interesting, is what I would say, and then we'll come back to Zytosanthinib first line, Hesham.

Sure, so thanks for the question, Graham. So we've got a robust approach to intellectual property. You'll see on Charlotte's slides later a little more detail on this, but I can talk about the additional intellectual property that we have in our hands today and potentially will have in the future on Cabotegravir. So let's look at six times the early treatment, so Cabanova that's in the market today. We've got additional protection now granted through to 2040 for that asset. We've then got three times the early treatment. Again, we've got additional protection pending through to 2047. and then when we come into six yearly prevention, we actually have the patent granted to 2031, we don't have an additional coverage for that asset. And then three times yearly prevention, we've now got secondary patents pending, which takes us out to 2045. So it is an incredibly difficult medicine to make and to bring ropivirine and cavitagravir together in the treatment space enables us to have quite a moat of intellectual property either. available today, or patents that are pending, which are broad and cover both the combination of the two, how you make it, and obviously the original composition of massive patents. So we feel really confident in the future of our IP to protect the assets that we have in our hands and in our pipeline. Just so we don't leave, because we're on the topic of IP, the H184 and 499 out. the base patents there run until hopefully when they're granted 2040 but we have additional patents that would again take us out to 2047. Regis do you want to just talk a little bit about how challenging it is to make these medicines?

Yeah I had no idea I would be describing the process this afternoon but we make the API in Singapore quite a standard process long chemistry, synthetic chemistry then after you bring it in UK where you do nano milling When you have finished the nanomelene, you will do gamma irradiation. When you have finished the gamma irradiation, you bring it back, you're going to fill it as a sterile product, you're going to gamma irradiate again, and you're going to inspect it, and then you're going to inject it. So, if we do it, we are not the only one. Someone else can do it, but not everyone. Thank you.

Thanks, Rizis. Kesha, first line. and maybe just fill in some insights we've got as part of the due diligence process talking to physicians and again we had insight into the regulatory exchanges as well so over to you Hesham.

Yeah thank you Luke. Yeah I'll start off first by saying of course that the phase one study has actually been recruiting additional patients in that first line forward as well too. I think the key really when we think about first line is the fact that we need the additional follow-up to be able to show that duration of response and that durability of response which I think is really critical for regulators as well too. With that in mind I think probably what I would probably focus on and point to is really when we look at the comparisons of the efficacy especially in this TKI naive patient population you look at the duration of response more than 12 months it's really at about maybe 96 percent For example, the GI side effects including diarrhea, nausea, vomiting and then even, I would say, when we look at some of the CNS side effects as well too, just given how selective and TREC-B sparing the drug is, including on dizziness, where we see, of course, with teletrecinib about the 22% incidence versus 12% only with cetacanthinib as well too. So I think we feel pretty confident about the first line approach from a regulatory standpoint. We're expecting a filing probably before the end of the year and then hopefully a regulatory decision in 2027.

Our next question comes from Steve Skalda at TD Cohen.

Please go ahead. Thank you very much. Relative to the general medicines guidance decrease, it was in part attributed to the soft environment. I'm curious what emerged in the last three months that led to this softness. Specifically, the company signed the agreement with CMS on June 15th. So were there any details of that agreement which were negative surprises? Thank you.

Thanks, Steve. Nelid, could you hear that?

I think so.

A little bit of an echo.

Yes, okay, so I think, so look, this is a portfolio of mature, older assets that continue to be in many regions under pressure, under pricing pressure, you know, generic medicines coming on board. That's one element. The other element is trilogy. and I think you have seen, we spoke about this in the first quarter already, we do see increased abandonment rates in the US for Tralogy and Tralogy is not the only one, it happens to actually all the assets in the CIT class. that is easing definitely but overall that level of abandonment the trajectory is going down but it's at the higher level than what we have seen in the previous years and to some extent that is contributing we mentioned that we expect this to now be removed in the second half we expect the growth to come back but it influences the whole year and I would just ask Julie if she wants to add

I think that's a perfect summary. We've obviously seen GenMed under some pressure in Q1 and the pressure increased slightly in Q2 so the full year view reflects that. I think very importantly we knew Tralegy would be under pressure in the first half and Tralegy has been the asset that's been growing double digits so it's taken away some of the strength in GenMed that we had before. So in the second half, we're anticipating there'll be less abandonment going on and we haven't got a tough comp like we had in Q2 because of the rebate and return adjustment. So I think that's a summary.

And there's a little bit of mix, of course, as the CIPD component becomes more. Peter. Thanks, Dave.

Thanks, people at BNP. Just a few for Tony. Just what timelines are you working to ballpark to get your people into Cambridge? When it comes to this new accelerated R&D strategy, have there been, I don't mind if it's not, the answer is no, but have there been any notable leadership changes to your team in the last 12 months? And then just specifically, when it comes to your B7 targeting ADCs, they are competitive, we agree with you. but there are a lot of others out there and in many cases they're ahead of you so as part of this accelerated change in late stage development and the nine studies you're doing are there any indications you'd call out where you think you could be first to market as a B7, A3 or 4 targeting ADC?

Okay, let me start on Hesham. I'll give you a chance to have a think about where the B7H3 and 4 question might go. First of all, in terms of Cambridge, remind me, there's three questions in there. The first question was... Yeah, time frame became... Time frame, early 29. We want to move the whole group and the first building is up. There are two more to go up, but early 29 is the plan for that. No immediate changes to my team. I've elevated one person. Our head of ClinOps now reports directly to me and that's all consistent with the way we're operating the business in R&D. She is an experienced leader and somebody we acquired actually from AstraZeneca so she knows how to find the Cambridge biomedical campus. In terms of where you will see changes and we will probably introduce you to some of these folks in the second half of the year when we do some of the earlier updates on research are the folks who report through to my colleagues who are here with us today. We continue to hire really exciting new leaders in MD PhDs who are still clinically practicing individuals. These are the folks who are helping us, for example, to integrate across different data layers. So I'm delighted with the progress we're making in really bringing the patient right to the center of our thinking in early research. In terms then of the ADCs and with regards to acceleration, look, before I give Hesham the opportunity to talk about which of the programs we see as coming first, I think it's worthwhile underscoring what we see as an emerging picture for both molecules, both in terms of their overall quality for response rate and now the first OS data, as you heard from Hesham, for for Mores, together with an emerging, not yet fully qualified, but I think advantageous selectivity profile. And since Regis is in the room, I'll also mention the fact that our experience with BlendRef has set us up very well with regards to ensuring manufacture of these molecules, which is not the most straightforward proposition. But Hesham, you might talk about some more specifics on where we see accelerations.

Yeah, I'm happy to, Tony. And I think probably starting out first to say, It's not always about being first. I think there are a number of different variables when we think about these ADCs that we have to take into account. I think the first one really is the type of technology platform that you have. I think we're pretty confident about the fact that we have a well-validated linker payload technology. We're seeing that in the data sets that we're generating. I think the second is, you heard me talk a little bit about the fact that we've got, and Nina touched on this as well too, we've got different sources of data that not everyone has access to. We've got large amounts of data that have been generated in China with both h3 and h4 and then we're complementing that with the data we're generating across our own development programs more than 600 patients for h4 more than 930 for h3 and that gives us unique insight in terms of not only which indications to pursue which ones not to pursue and I think the third really is more around how we're thinking about translational strategy. To me at least probably it feels like the most differentiated ADCs across different patient segments or tumors are going to be the ones that could better enhance the treatment effect relative to the ITT and that comes through a really good understanding of the biology but also how the drug actually works in the context of not only target expression but also the linker and the payload and their importance in terms of how sensitive the tumor is to them and so we've got a multi-pronged strategy where we're actually looking at a number of different technologies and platforms for biomarkers that we think will certainly be important in that regard and then of course the execution is clear in terms of the pace and the scale which is important but I would say probably maybe for B7A3 the one maybe tumor type that I'd highlight that could be of potential interest and could be differentiated is actually non-small cell lung cancer. We're seeing the data, of course, that was presented at ACR, 47% response rate in combination with PD-L1 in a PD-1 pre-treated patient population. Again, it's data from China. We have to validate it. We've got ongoing phase two to do that and help confirm it, but it could certainly be an interesting opportunity that maybe is more unique at least in the short term.

And then probably worthwhile just quickly particularly for mores where the data is more advanced. I think it serves to take a look across the various patient characteristics and dose use for our molecular relative to our competitors there to get a sense of what Hesham is talking about in terms of the emerging properties of mores relative to others.

Yeah and I'd also add we've got a team you know the layers below that have a fantastic correct record across a number of companies in terms of navigating programs Right, we've got time for one more question. Simon, then we'll go for a break.

Thank you. Simon from Rothschild & Co. Redfern. I'll try and be quick. A big picture one on R&D. It's clear that R&D at GSK in five years' time will be in a very different place in every sense of the phrase. But I just wondered if you could give us an idea of the moving parts between the additional resources that's going in productivity changes and really the key question is how are you going to measure that change and improvement and how will we see that measurement improvement beyond simply looking back in eight years and thinking GSK accomplished more than they did in the previous decade where is where are we now uh where were we where are we now and where could we be by the end of the decade thank you okay wow that's certainly another one minute answer um

So look I mean where were we was a very distributed portfolio pointing to opportunities of little value and you saw that we've transformed that substantially in the past four years. Also that we have a portfolio in which there are a number of meaningful life cycle innovation opportunities so that I'm getting more out of each asset. They're moving quicker, we're 25% quicker than we were in upper quartile as far as that's concerned. The decisions that we make about that portfolio and in terms of BD as well are made by exactly the same people who make their decisions on the early stage portfolio. So you should expect to see the same discernment in terms of highlighting and accelerating assets for that as well. I will share with you at some point in time if you want the scorecard and how we evaluate individual areas of the business. I don't have time to Go through that in detail right now. What you will see hopefully is continued momentum towards the areas of significant opportunity and competitiveness in terms of either pace and for first in class or careful decisions for best in class agents and the best way I can illustrate that is through the portfolio that will be sharing today in early stages I could pick different examples across all of the parts of our business looking for example at how we execute our clinical programs the case in point might be as we apply more data there for example we're expecting to be able to half our study start up time by the time we get to 2028 so it would take me the next half an hour Simon to go through each one of the segments and give you the simple and the KPIs that we're using to judge progress there but I can assure you they are in every single group. They're a relatively small number because I don't like to give people the opportunity to hide behind long lists and it's extremely data enabled.

So the good news Tony is you've got 20 minutes at the coffee break to do exactly that. That concludes our first Q&A. If we didn't get to your questions please obviously know the people to find and we'll make sure that we get to your questions in the second round. and of course we've got time at the end as well because we want to make sure we capture and get your questions. So with that we'll have a break. Thanks guys. We'll see you back in 20 minutes at 35. It's a little less than 20. Thank you for watching. Thank you for watching. Thank you for watching.

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I think we are ready to start, thank you.

So welcome back and I now get to introduce Kavan, over to you.

Thanks Luke, good afternoon everyone, my name is Kavan Kabandi, I'm the Head of R&D at GSK for Respiratory Immunology and Inflammation. GSK is well recognized as the leader in respiratory medicine having pioneered multiple products across invitations notably asthma and most recently with the launch of Extensure the first ultra long-acting biologic to be launched in airways disease. However when we think about the largest remaining unmet need and the sheer scale of opportunity this is undoubtedly in COPD which is an area of Thank you very much. but it's steatotic liver disease secondary to MASH and alcohol where we see GSK continuing to innovate with efemisfermin and beyond. What's underappreciated though is that these two areas are much more connected than at first apparent. Serious chronic diseases with shared underlying inflammatory and fibrotic as well as vascular risk which frequently coexist. Patients with primary disease of the liver, heart and lung are also at risk of developing secondary pulmonary hypertension, a serious and much more expansive area than idiopathic PAH, for which there is largely no approved treatments. Together, these three areas form an unaddressed comorbid axis that carries a very high risk of mortality and for which GSK is strongly positioned to lead. So with that background, when we look at recent product developments at GSK, success has been demonstrated really as a consequence of mechanisms that stop the core inflammatory risk relevant to each disease. In areas like asthma and nasal polyps, these are primarily driven by T2 pathways identified by eosinophils and very well served with products like Nicala. Future innovation in these diseases will not come from marginal gains with new mechanisms, but from practical, real-world innovation from modalities that can help patients comply and persist on their medicines. Enter our ultra-long-acting portfolio with Extensure and ultra-long-acting TSRP. There is one overlooked T2-driven disease, and that's food allergy, where IgE targeting has only recently been shown to be effective and where we rapidly build on that observation and early commercial success with an improved, long-acting and potentially best-in-class approach with ozoreprobarbs. And that takes us to CAPD and non-CF bronchiectasis. Whilst an important subset of CAPD is T2-driven, most of it is not. and a different set of risk factors with distinct inflammatory, metabolic and vascular drivers are responsible for the disease progression. Here we do need mechanistic innovation and we apply our deep translational insights directly to late stage product developments, notably with IL-33. This bridges us to pulmonary hypertension that can of course result directly as a consequence of COPD but is a pulmonary vascular disease by definition with mechanisms of risk overlapping with COPD on the left and MASH on the right. So with COPD really at the center in terms of the greatest burden of disease, GSK's competitive advantage and bridging these two worlds of inflammatory risk, let's take a moment to consider the scale of the problem. and it's substantial. You might have heard these stats before, but when you see them contrasted versus enormous established markets like rheumatology, it becomes evident that we're only scratching the surface with only two advanced therapies in one subtype of COPD reserved for late stage disease. But with 400 million patients affected globally, over 20 times more patients than RA and 100 times more deaths annually, It becomes very clear that multiple product solutions are needed. So what do things look like for a patient with asthma or COPD today? The orange line of the top figure shows exacerbations and with them the step changes in lung dysfunction which in asthma leads to disease progression and in COPD brings irreversible loss of lung and asking in the red line below these are associated with surges in mortality. Short-acting biologics today are started late with poor persistence leading to disease progression in asthma and unfortunately hospitalisations and premature mortality in COPD. So what's the solution? Well, start biologics sooner and stay on them for longer. If we were able to move from 24 injections a year to just two and provide sustained coverage and protection, that would surely be the way to achieve this. and that's precisely what our portfolio is designed to do with extension launched in asthma and shown in the graph how we're approaching COPD a development program that seeks to sustain persistence but not just at the conventional points of treatments but with these unique characteristics of the medicine we have the confidence to start a third phase three study vigilance enrolling patients after just one exacerbations that's unprecedented for a biologic So the prior slide showed how Xtensura achieves greater coverage and clinical benefits in patients with T2 inflammation through earlier management and that's illustrated in the rubric here by extending across the grid horizontally. But I mentioned that in COBD we do need more mechanistic innovation to achieve greater coverage across different populations who have different types of inflammation and that's illustrated by extending vertically up the grid. Nicala was the first biologic to achieve a broader label owing to metrics which studied lower eosinophil levels while Matanay came in and showed efficacy for the most clinically impactful events, emergency department visits TSLP is a mechanism that by design is able to extend into intermediate T2 inflammation and where data indicates efficacy in those with eosinophils as low as 150 but not lower and that takes us to IL-33 where we probably need to ignore Eosinophils altogether as this mechanism cuts COPD in a fundamentally different way and that's easier to visualize. All patients with COPD have innate immune dysfunction and a propensity to T1 and T17 inflammation. These patients are older than those with asthma, they're sicker and they have a high burden of vascular and metabolic disease represented on the right-hand side of the slide. A proportion of these patients have truly high T2 risk and a further group have mixed intermediate levels. This is the orange and middle overlap segments of the slide and this risk is well addressed with IL-5 and T-slit biologics respectively. But how do we get to the backbone of pathobiology in COPD, the blue plane in the slide? Well, a single, dual or even triple cytokine approach won't be the answer if they're targeting the wrong biology. This is where we need to get to the tissue, vascular and structural damage that results from repeat injury at the root of COPD IL-33 is expressed primarily on lung epithelial and vascular endothelial cells The dynamic barrier lining the airways and blood vessels These are the first tissues to be exposed to and then attempt to respond to inflammatory injury and our translational insights reveal how and when IL-33 governs this therapeutically untapped space. And so we're very excited to have a potentially best-in-class, long-acting and phase 3 ready products which will be deployed with the benefits of this deeper understanding. We predicted the early success now shown clinically for anti-IL-33 when stratifying based on mucus score. With the luxury of what we believe to be the most complete set of respiratory data anywhere in the world, over a thousand randomized controlled trials, several million patients with deep genetic and cellular profiling, and of course clinical interventional data in COPD with our product, we've designed pivotal studies based on patient profiles most likely to respond to IL-33. These will include factors related to stage of disease, by which I mean lung function, distinct from disease severity defined by exacerbation history, and other traits, and tested against new clinically important outcomes that can differentiate the product. Without disclosing too much, what I can share is that one of these pivotal study starts includes a cardiorespiratory outcome study. which we will start next year in partnership with a major cardiovascular academic research organization. In parallel we will complete our phase 2 study in non-CF bronchiectasis, an enormous market with no approved biologics and where we're positioned to be best in class with IL-53 as well as testing combinations with TSLP which our AI enhanced models predict could provide synergistic efficacy. So, we're looking forward to coming out of IL-33 stealth with conviction and material differentiation. Our ultra-long-acting TSLP program has been significantly accelerated by nine months across three indications, now positioning this asset to start six pivotal Phase III studies, the PERSIST program, integrating data from a GSK-sponsored Phase II study in asthma, the NASARE study, alongside data from our partner, Hungry, who study nasal polyps. This gives us dosing and pharmacodynamic data to confidently advance the first ultra long acting TSLP across all major indications, asthma, nasal polyps and COPD. Our BD strategy to access de-risk mechanisms with a high likelihood of success allows us to jump directly to testing for product differentiation rather than mechanistic relevance. And this is reflected in our deals since January. Ozzy Reprobats builds on the proven efficacy of IgE in food allergy and CSU but provides materially broader eligibility for those 25% of patients contraindicated for ZOLAR because of their weight or high IgE levels and an optimized solution for all with three monthly dosing. This will be transformative for the prevalence, adolescents, population and children. This class has had a remarkable first launch within the first two years with ZOLAR. now Rocha's fastest growing products and Ozu is positioned to provide an objectively improved profile whilst benefiting from that momentum. This overlooked space has understandably garnered interest and activity since our deal but Ozu is the most advanced next generation product with clinical efficacy data in CSU which importantly included an active arm with Jolar which didn't perform as well as Ozu. The program has rapidly enrolled in phase 2 and has now recruited the sample size necessary to progress to an interim analysis which will enable phase 3 starts in both food allergy and CSU by the end of 2027. For HS235 we build on a new and transformative class of active entraps in pulmonary arterial but with an improved molecule that can both remove the liabilities of the incumbents in group 1 pH namely bleeding but what's equally exciting is the potential to unlock the full value of the mechanism which extends to reducing inflammation, insulin resistance and reducing visceral fat all of which are substantial drivers of risk in group 2 and group 3 pulmonary hypertension secondary to chronic heart and lung disease. Whilst this programme is relatively earlier than other products being presented, we've seen evidence to support both the safety and efficacy profile described in the Phase 1b study. And I can share today that we've rapidly converted this post deal to Phase 2b starts that have now been initiated for both Group 1 and Group 2 primary hypertension. And that takes us to our hepatology portfolio. Succinctly, Our portfolio is pointed to the three major causes of liver-related cirrhosis and mortality. Chronic hepatitis B, metabolic dysfunction associated with sciatic hepatitis, and alcohol-related liver disease. All of these diseases have poor outcomes and inadequate standard of care. There's no approved treatments for alcohol-related liver disease, one liver-directed treatment for MASH, and no therapies that can drive cure in hepatitis B. but starts with Bepiribircin, our first in class ASA for hepatitis B. Our program was ambitious, designed with a primary endpoint of functional cure, the very highest bar. This is best illustrated in the comparator arm in B-Well, where what's labeled as placebo actually represents the standard of care, 48 weeks of treatments with a nucleoside or nucleotide analog. And in that group, We saw zero patients achieve the primary endpoints, functional cure, in the ITT population. Zero patients achieve functional cure in those with baseline surface antigen levels less than 1,000, and zero patients achieve an effect with surface antigen levels under 100, which would be consistent with the definition of partial cure. In comparison, Bepi achieved 19% cure in the ITT population, 26% in those with surface antigen at baseline less than 1,000, and importantly, when you include partial cure, a response that's been reported in population studies to improve long-term outcomes, almost one in two patients studied in the ITQ population received a response that would predict clinical benefits. And that increases to 62% in those with circumstantial levels less than 1,000 at baseline. Of note, this opportunity consolidates in three key markets, China, US and Japan. You can see the epi and scale of the opportunity on the slide in the bottom left, which is vast. So, a very exciting opportunity reflected in a suite of expedited regulatory designations setting up near-term expected marketing authorizations and product launches. And then FMS Bermin, our potentially best-in-class FGF21 analog in an area of major unmet need in stereotopic liver disease. Let's start with the class. On the left, in F2F3 MASH, you can see greater benefit on improvements in fibrosis with FGF21 analogues when compared indirectly across studies with GLP-1 agonists, such as semaglutide, and thyroid hormone agonists, resnetron. Moving to the right, in cirrhotic MASH, where currently there's no approved treatments, you can see placebo-adjusted changes that are unprecedented with this class. showing the ability to reverse histological fibrosis and move a patient from cirrhotic to non-cirrhotic disease. In contrast, the Maglutide showed directionally worse effects versus placebo. And then within the class, we selected FMS-Firmin over other products all available at the time of acquisition based on its best-in-class credentials with monthly versus weekly or bi-weekly dosing regimens and since the deal FMS Furman has reported the fastest observed signal for an anti-fibrotic benefit of any in the class with fibrosis biomarkers improving as soon as four weeks after treatments and for which we've designed our pivotal program to substantiate as a potential additional differentiator. For all these reasons we're committed to realizing the full value of this potentially transformative product. Seeing us initiate the Zenith studies to F2F3 MASH, both recruiting since earlier this year. And we have now initiated the F4 cirrhotic MASH program, the Nebula studies, only in the last two weeks. And our phase two study in our correlated liver disease, All Star, has just had IND approved and will start this year. So, a portfolio of specialty products pointed to serious and prevalent diseases with renewed discipline to truly focus on areas of greatest commercial value and in turn prioritize and accelerate those programs. Unprecedented data for Bepiravircin which resets the bar of efficacy in chronic hepatitis B with functional and partial cure where the standard of care fails to achieve either. A portfolio in COPD that will provide modality and mechanistic innovation providing greater coverage and protection for a disease that's the third leading cause of death globally and with material acceleration of programs like ultra long-acting TSLP and with both molecule and potential evidence and claims differentiation for our best-in-class long-acting IL-33. FMS Furman advancing its speed across a comprehensive phase 3 program which will capture the unique breadth and potential for this mechanism across all stages and etiologies of steatotic liver disease. F2 and F3 mash, serotic F4 mash, our correlated liver disease and actually potentially beyond with a molecule that has best-in-class properties. And a portfolio enhanced by BD deals that bring best-in-class products, de-risk mechanisms and which all fits within an axis of disease that physicians recognize that have yet to be applied to drug developments. And that's a gap that GSK is uniquely positioned to address. With that, I will hand over to my colleague Sanjay to cover vaccines.

Thank you, Kyla. Good afternoon, everyone. My name is Sanjay Granathan. I head the global vaccines. and infectious disease unit in R&D. Vaccines have a massive impact on public health. That's not new. We've known that for decades that preventing disease takes real pressure of health systems. But here's the thing. The science and economics around vaccines are shifting. They're pointing to something much bigger than we give them credit for. So let's dig into why this is the case. These are stats that always surprises people. Vaccines make up a tiny slice of our healthcare spending, less than 1% of the healthcare budget in high-income countries. And yet that investment, return on investment, is roughly 19 times of what you put in. We already know how valuable it is to prevent an infection. What's missing in the economics is the big picture. The science is starting to catch up. We used to think of an infection as something that happens and then passes. It turns out that's not the whole story. A lot of infections go dormant in the body, and some of them seem to be tied to long-term health effects, even chronic disease down the road. So preventing that initial infection might do a lot more than we thought. It could lower your risk of things like heart disease and dementia later in life. So the opportunity here is simple. We need to build the evidence that turns this potential into something that's recognized and reimbursed. and GSK is in a great spot to lead on this. We have already a broad, well-established vaccine portfolio, Shingrix, RxV, flu vaccines, a strong meningitis franchise and a deep lineup of pediatric and travel vaccines. But more importantly, there's real room to expand beyond what these vaccines can already achieve. Shingrix is our best example of this. We have a huge amount of real-world experience. Over 116 million adults have been vaccinated with Shingrix since it was launched nearly a decade ago. There's a growing body of evidence that herpes viruses, including herpes zoster, the virus that cause shingles, can influence cognitive decline. So why would that be the case? Well, the shingles virus doesn't actually go away after a chickenpox infection. It just goes dormant, hiding out in the brain neurons. When it wakes back up, it can spark local inflammation, and that inflammation seems to play a role in cognitive decline over time. So by keeping the virus from reactivating in the first place, Shingrix may end up slowing down that decline. But there's likely more to the story. We think Shingrix's adjuvant, AS01, might be doing some extra work behind the scenes beyond just blocking viral activation. It could possibly be dialing down inflammation more broadly, including the kind of age-related inflammation that builds up in the brain. That's right, it could mean Shingrix is nudging the whole trajectory of neuroinflammation in a healthier direction. We've now seen through several observational studies, risk reductions of dementia symptoms up to 50%. This signal is now being put to test in two big pragmatic studies in Finland and Denmark covering around 200,000 people with results expected from 2029. We're not only seeing this as how Shingrix affects neuroinflammation, but as we go to the next slide, when we look at cardiovascular risk, it gets even more interesting on Shingrix's broader protective effects. Real world data from several independent sources, Veterans Affairs, Kaiser, Optum, Trinitex, all point the same way. Older adults who got Shingrix saw about a 25% drop in major adverse cardiovascular events, or MACE. So why should that be? It turns out the Shingrix virus itself isn't exactly harmless to your blood vessels. It can damage them, Thank you very much. Cardiovascular disease is expected to nearly double by 2050, with costs in the U.S. alone set to top over $400 billion a year. We believe the real-world evidence you see on this slide is compelling enough that we are launching a formal Phase 3 randomized controlled trial this year to nail down whether this is actually causal, not just correlational. We expect the study to start soon. Another opportunity to improve outcomes in older adults is to prevent influenza infection. This disease burden of influenza is significant in adults, in older adults with the majority of hospitalizations occurring in older adults. It's a segment we've not previously competed in. We know from published literature that influenza vaccination reduces cardiovascular disease burden and respiratory complications. Underpinning the theme of broadening the protective effects of vaccine, especially in older adults. As you can see from this visual, currently available flu vaccine effectiveness has varied from 20 to 60% over the past 15 flu seasons, illustrating why there's a true unmet need to improve flu vaccine effectiveness. We believe there's an opportunity using our mRNA technology to establish benefit over current standard of care. We can optimally leverage this technology, its differentiating characteristics, to develop our next best-in-class flu vaccine. We will present our positive face-to-results at the options meeting next month, where you'll hear the exciting data. So let me conclude. What's our focus, and where is our focus? Our focus is expanding the role of vaccines, the vaccine's play, in helping older adults living a longer and healthier life. If you can back that up with strong clinical outcome data and a real understanding of the biology behind it, it could support future labels that reflect these broader benefits. And that changes things. It gives healthcare professionals more confidence to recommend vaccination and give more people reason to get vaccinated no matter what their current health status is. What really excites us is the growing science connecting infection to chronic disease. It makes An already strong economic case for vaccination, even stronger. Opens up new opportunities across a portfolio, and thanks to Shingrix, it gives us a real working example of how to unlock that value and help shift the trajectory of chronic diseases for older adults. It's now my pleasure to hand over to Charlotte, who will talk to you about our HIV business.

Thank you Sanjay. I am Charlotte Allerton, head of R&D and CSO for Veep Healthcare at GSK. Despite decades of progress, HIV remains a major unmet public health challenge. More than 40 million people are living with HIV globally, and in the US, around 30% of people diagnosed with HIV are not virally suppressed, equating to approximately 400,000 people The majority of whom are still taking daily oral antiretroviral medications as their standard of care. Real-world barriers such as adherence and stigma continue to negatively affect health outcomes, quality of life and transmission risk, reinforcing the need for long-acting medicines that address these challenges while delivering public health benefit and significant revenue growth. Treatment represents 90% of the current HIV market, the largest unmet medical need, and remains our priority. By 2035, we expect this market to be worth approximately £25 billion, with growth driven by uptake of new long-acting regimens, despite daily oral generic century and pricing pressure. For prevention, we expect this market to be worth approximately £6 billion by 2035. Across both treatment and prevention, long-acting injectables are the fastest growing segment and we are leading this market transformation from daily oral to long-acting HIV care that improves patient experience, supports adherence and drives sustained competitive growth. We have been at the forefront of HIV innovation for nearly four decades. leading transformational changes in patient care through the first two drug oral therapies, and then Cabinuva and Aperture, the first to market long-acting injectables for treatment and prevention. Our current portfolio and future pipeline are built on the foundation of Integrase Strand Transfer Inhibitors, or INSTIs, which are trusted by healthcare providers worldwide due to their superior efficacy, long-term tolerability, high barrier to resistance, and they form the basis of over 80% of treatment regimens globally. Today we will focus on our near-term growth drivers, three times a year treatment, two times a year treatment and three times a year prevention. However, as you can see beyond these transformational opportunities, we will continue to innovate to address the health of people impacted by HIV for many years to come. This includes best-in-class long-acting orals, which we see as an opportunity to reach the around 30% of patients who our market research suggests may not choose injectable treatment. We have initiated a phase 1 study for VH359, a capsid inhibitor, and have multiple potential weekly oral instees and capsid inhibitors in preclinical development. Our leadership in long-acting will continue to fuel our growth. with each innovation building on our expertise to shape the future standard of care and reach more people impacted by HIV. Given our lead, we will have launched our second and potentially third long-acting injectable treatment before anyone else centres the market. Cavanuva is the first and only complete long-acting injectable HIV treatment. More than five years' worth of real-world and clinical evidence continues to validate the strength of Cabinuva, showing robust antiviral effectiveness and barrier to resistance comparable to daily oral medications, with strong persistence out to two years and substantial patient preference compared to oral therapy. In addition, Cabinuva demonstrated superiority over oral standard of care in the Latitude study, delivering nearly two times lower regimen failure and four times lower virological failure leading to early study termination due to overwhelming efficacy in this suppressed high-risk HIV population with adherence challenges. The real-world data in viremic patients is also compelling and we look forward to seeing data from our CROWN study in the second half of 26 assessing Cabinuva in viremic patients with adherence challenges to daily oral therapy. The entirety of this data shows the power of Cabinuva to lead the market growth in long-acting injectables through addressing preference, stigma, adherence and reducing the burden of daily oral therapies, supported by a robust IP strategy with Cabotegravir NCE patent protection into 2031 and additional null patent protection now granted into 2040. As the first mover in long-acting treatment, we have built the market from the ground up, establishing the evidence, infrastructure, provider experience, and patient confidence needed to accelerate the adoption of future long-acting injectable innovations. We are now focused on franchise growth, continuing to address stigma and adherence challenges, while meeting patient and healthcare provider preference for less frequent administration. The profile of our three times a year treatment, constituting novel formulations of cabotegravir and rapogarin, is compelling. It builds on the proven efficacy and trust experienced with Cabinuva, takes 365 oral daily treatment days down to just three injection visits per year, doubling provider capacity compared to Cabinuva, enabling clinics to serve more patients without increasing infrastructure. and this competitive profile is underpinned by a robust IP strategy with additional patent protection pending into 2047. I am pleased to share that Quattro, our three times a year phase three registrational study in suppressed switch patients has begun, supporting potential approval in 2028. We remain confident that three times a year treatment will be transformational, not incremental. Making long-acting treatment easier to choose, deliver and sustain. Unlocking substantial switch opportunity from both oral therapy and existing cabanuba, which will drive long-acting injectable market growth. Having set a high bar with our three times a year treatment, we are driven to keep innovating for people living with HIV by delivering a two times a year long-acting injectable treatment. Our preferred regimen is the combination of our third generation INSTI, VH184, with our novel capsid inhibitor, VH499, a combination with NCE patent protection into at least 2040 and additional patents pending into at least 2047. We believe this regimen can set a new standard of care for a broad HIV population. bringing confidence in efficacy and a high barrier to resistance while further addressing adherence challenges. BH184 is currently in a Phase 2B clinical study where we have seen rapid patient recruitment reflecting the community's interest in its third generation industry profile. Our differentiated capsid inhibitor BH499 will commence its Phase 2B study in the second half of 2026. And we have a bold plan to get to Phase 3 in 2028 and approval by the end of the decade. Combining operational insights from our ongoing three times a year Quattro study and utilizing the entirety of our phase one and two data to select optimal doses and formulations to achieve what we believe will be a practice changing profile. The data on this slide represents a subset of evidence of that practice changing profile. The chart on the left shows VH184 retains superior potency Thank you very much. The graph on the right shows VH499 does not cause the CYP3A mediated drug-drug interactions that can lead to safety concerns for patients taking common concomitant medications or recreational drugs. It shows that VH499 had no effect on the pharmacokinetic profile of midazolam, the FDA recommended probe for exploring CYP3A drug-drug interactions. This data, combined with 499 and 184's strong efficacy and encouraging tolerability, gives us a combination that is not just less frequent, but clinically and commercially differentiated, maximizing patient reach and transforming options for people living with HIV once again. Now moving to HIV prevention. The unmet need is significant. Despite the 2.2 million people in the US that could benefit from prevention, Only 25% use it. Daily oral persistence remains low, creating a major opportunity for long-acting options that better fit people's lives. Our three times a year prevention candidate, which contains a new formulation of cabotegravir, builds on aptitudes greater than 99% efficacy and extensive real-world experience, and is protected by a robust IP strategy with additional patents pending into 2045. Six months after a single dose of cabotegravir and lenacapavir in our CLARITY study, follow-up data reinforced cabotegravir's highly preferred injection profile, with fewer, less visible, and shorter-lasting injection site reactions, whereas 90% of participants continued to report lenacapavir-associated nodules at six months, with 20% being reported as severe over that time period. Delivered through a single intramuscular injection, R3 times a year prevention has the potential to combine strong tolerability, a favourable drug-drug interaction profile, a dosing schedule aligned to routine sexual health visits, and the fewest maintenance injections per year, reducing treatment burden and supporting long-term persistence. With registrational study data from Xtend4M, anticipated in the second half of 2026, and approval in 2027, we remain confident it represents the optimal prevention option for both patients and providers. To close, HIV remains a significant, persistent and unresolved public health challenge. The market is moving towards long-acting, the innovation we have built and lead, with INSTI at the core to drive the market transformation. Cabinuva demonstrates the power of long-acting treatment and creates the foundation for continued innovation and a pipeline that keeps raising the standard of care. Our near-term long-acting injectable growth drivers are clear. Three times a year treatment to unlock the next wave of growth, targeted for 28 approval. Two times a year treatment, novel molecules, designed for differentiation, planned for phase 3 start in 28th. and Three Times a Year Prevention optimised based on patient and provider feedback targeted for 27 approval. As HIV care continues to evolve, we are uniquely positioned to shape where the market goes next, combining scientific leadership, long-acting innovation and deep patient insight to deliver the next generation of treatment and prevention options. That brings us to the end of the R&D part of the presentation and I will now hand over to Julie to share more on the funding of Accelerate Growth and our outlooks.

Thank you very much Charlotte and also to all my R&D colleagues. So as you've seen GSK has a broad and rich portfolio of opportunities and the purpose of this section is is to show you how we plan to fund it. Moving on to the next one. So one of our three priorities is to simplify the way we work. And this will be enabled by the Accelerate Growth Program. We've identified 1.9 billion of cumulative annual benefits to be delivered by 2029. And the majority of these will fund the investment opportunities outlined by Tony and his team today. accelerating seven assets across 18 indications and with more than more than 20 phase three trial starts in 2026. Now a proportion of the savings will also drop through strengthening the margin through the dollar tag reveal loss of exclusivity period which is 28 to 30. The program will deliver incremental sales from 2030. It has a very strong IRR and it will be implemented with financial discipline as usual, ensuring we retain capacity for business development. Turning to the details of the programme, we expect 90% of the cumulative annual savings to be delivered by 2028 and we have undertaken an enterprise-wide review to identify opportunities with processes redesigned and enabled by tech and AI. Support functions and key processes across the organisation will be streamlined for efficiency and impact. Procurement will be enhanced further to deliver maximum value. And we will also be reallocating resources from mature brands towards the key specialty growth drivers. And finally, there will be further automation and simplification of the supply chain and the network to align with the evolution of our portfolio. the program will cost 2.4 billion sterling to be reflected in adjusting items of which 2.1 billion is cash and the payback is two and a half years before the reinvestment we have a compelling track record of deploying cash in line with our capital allocation framework first invest for growth and second shareholder distributions all underpinned as you know by a strong investment grade balance sheet since the start of 2021 we have delivered more than 40 billion of cash generated from operations we've deployed 18 billion to invest for growth by way of capital expenditure and business development we have distributed 16 billion to shareholders through the dividends and the buyback and we've reduced net debt through this period by 6 billion sterling, decreasing net debt to core EBITDA to 1.3 times. This represents a considerable transformation of GSK and considerably improved cash generation and a significant reduction in net debt has led to the strengthening of our balance sheet, affording us the optionality to execute BD and further strengthen the pipeline as you've recently seen through the acquisition of Newvalent. We also have a strong track record of delivering profitable growth and increasing returns, whilst continuing to increase the investment we've placed in R&D. So from 21 to 26, we are on track to deliver yearly sales growth of 8%, operating profit growth of 13%, and more than a 540 basis point improvement in the margin. Now this is all whilst R&D investment has stepped up. Increasing more than 50% to now more than 7 billion and supporting a doubling of the phase 3 starts in 2026 as Tony outlined. So looking ahead to our longer term outlooks and the impact of accelerate growth. We remain committed to our outlook of more than 40 billion of sales in 2031 with more than 50% of our business in specialty medicines. Our operating margin is now expected to be stable to improving through the dollar tag of their loss of exclusivity period, supported by a number of things. First, specialty continues to grow as a proportion of the portfolio. Second, we were driving increased productivity gains across the business. And third, part of the savings from the program overall will drop through to the margin in that three year period. Growth is then expected to accelerate from 2031 onwards given the portfolio of products and the opportunity for further BD, the latter of which would be incremental to our commitments. This program allows GSK to build on the strong foundations we've laid over the past five years and accelerate growth from 2031 onwards. Thank you and I will now hand back to Luke for final words.

Thanks Julie. Next slide please. So today I opened by saying that our focus was on products and growth and this slide here shows the pathway we are building with our products to drive growth and with it delivering long-term value. So the presentations from the team today were designed to give you greater insight into how we're actually going to make that happen. and to re-anchor you, at the start of the day I outlined that we would demonstrate to you the following. Firstly, confidence in our ability to drive the business now and beyond to 2031 by showcasing our late stage pipeline and our focus on defined value propositions and by providing some detail on how we are reallocating capital and resources to change and invest in R&D. With that, I think we're going to go to questions. I'll ask Richie. You guys are quick. I wouldn't want to get a gunfight with you. So we'll bring the team up. So Julie, Nina, Charlotte, Kevin, and I think Sanjay as well. And as we said earlier, raise your hand, you guys clearly remember that. So Zane, I think you were, you want to go first? And then just wait while everyone sits down. Great. Zane, over to you.

Great, thanks for taking the question. Zane Abraham, David Morgan. First question is just on the 2031 target and beyond. I think Julie sort of ended with a comment on it in terms of 2031 now sounds like it's organic, but just to confirm that new valence included in the 2031 are greater than $40 billion. And then the target for, or ambition for, accelerating growth beyond 2031. You mentioned that it's organic in terms of delivery and your commitments, but how much of that is dependent on BD in terms of the ambition beyond 2031? That's the first question. A second question is just a follow-up on 2027 margins, because I think the path on 28 to 30 is relatively clear. And you'll have the cost savings that will help offset some of the dollar tag value. But next year you've got the Gilead royalty going in Q4. Charity Grillo IRA impact potentially and R&D you've mentioned all significantly outgrow sales so just how should we think about 27 in terms of margins I think consensus has got margin expansion so what are the other drivers that could get towards margin expansion?

Okay so in terms of the first question related to New Zealand and so then what we we've emphasized that we are totally committed to more than 40. Obviously the New Zealand acquisition happened recently and we've now got accelerate growth. Accelerate growth the sales start in 2030 but they're quite minor in 2030 it's more of a longer term play but no no we just we'd like to emphasize that we are saying we will deliver and we will deliver more than 40 but we didn't want to get into minor increments each way along. I think as Luke mentioned, it is a portfolio. We obviously had the CamelPixent used just over a week ago but it is a portfolio and we believe we will deliver more than 40 overall when you take it asset by asset. Everything we do as well, I think as most people know, is PTRS adjusted, probability of technical and regulatory success but inevitably you get movements in the portfolio now that we've built to build that optionality and then none of it at all is dependent on what you might call new BD so if we do further deals which we do intend to do we've got capacity to do them as Luke's outlined they would be incremental on top if that answers that question And then in terms of the margins, I got this question in the break actually from quite a few people. So we have guided the margin to the end of 2026, which is more than 31% at 25 average exchange rates. We then guided the dollar tag of the period because we knew and appreciated that investors were quite concerned about that period because of the profitability of HIV. so we did an extensive amount of work as a team to basically understand how we could underpin that margin through that period but we did not want to get into guiding a margin every year so we gave the assurance based on a whole series of factors that we could hold the margin stable through the dollar tag reveal loss of exclusivity what we're now saying because this program then generates the additional savings which total 1.9 billion by 2029. It allows us to drop through some of those benefits to give not just a stable margin, but the optionality to also have an improving margin through that period. And it builds 28 to 30. So the period when dollar tag river hits the most, it's most protective.

Thanks very much. Great, thanks. Okay, I'm trying to think, have you had a question before? And then we'll go James and then anyone at the back, okay.

and Naresh Chauhan from Intron Health. Thanks for taking my question. Just one on vaccines. It seems that the pharma business and the vaccines business are going to have increasingly different outlooks in terms of innovation, growth rates, capital requirements. So how weighted are you to continuing to own vaccines, which presumably, if they were separated, would have quite a lot of value and would further simplify the business? Good answer is very wedded.

I mean, the capital intensity really is in register shock. I think the main challenge with vaccines, frankly, is the paucity of novel targets of innovation. But again, we're trying to capitalize on that and some of the signals that we've observed there. But I mean, it's a fantastic business. It's very hard to get into. Okay, it's under short term pressure, frankly, because of politics in some locations and post COVID hangover. But frankly, I think if you look at the media for longer term, It's a very durable business with very high barriers to entry. The question is, what can we do to be more operationally effective? How do we make this plant more productive? And then when we do see innovation, how do we make sure that we're participating in it faster and more aggressively than and others. So long story short we like the business but again the hierarchy for us in terms of capital allocation you can see is specialty and again that's why we're highlighting that from 2031+. Thanks and then James and then I think Sean will go to you. Is that Sean up there? I think, yep, Sean and then I promise we'll get to everyone.

Great, thank you. So James Gordon-Barkley, two on HIV and one quick one on R&D. So on HIV, I think the previous plan was to have a six-monthly prevention product. I think it was in 2028, but I couldn't see it on the slide. So are you not doing six-monthly prevention anymore? And on treatment, I think it was six-monthly treatment, 28 to 30. So I could see that you're starting the phase three in 28, but when do you think that launches that? Beyond 29, so post-dolotegravir LOE is when you have a six-monthly treatment. and then also just clarification of orals I think you also talked about but when do you think you could have a weekly oral or a monthly oral on the market please? And then the final one just squeezing this, R&D spending, I think before you said R&D would grow faster than sales was the way you put it, should we assume that's the assumption that effectively you spend less on SG&A but R&D keeps on growing faster than sales, how should we model that please?

Sure, I mean long story short, yeah we want to drive R&D and there's the portfolio changes You know, when I joined GSK, we launched a few thousand people in the US. You look at Zionist Anthony, we're talking 10, 20 people. So, Charlotte, over to you. And then, Julie, if you want to add anything on that one as well.

Great, thank you for the questions. I'll start with the two times a year prevention. So our market research in prevention says to us that really three times yearly is the optimal. I updated on the three times yearly today with, we hope, data in the latter part of this year to support approval next year. it aligns very well with medics preference in terms of bringing people into the clinic and wellness checks and sexually transmitted disease checks you know that's how we know there'll be a subset of the market that will still seek for a twice yearly and so we remained committed to that as a line extension and we have actually a pro drug of capotegravir that we're taking to the clinic during the latter part of this year we will look to develop that using PK bridging approaches and we'll update on timelines on that more in due course the twice yearly treatment you asked about potential timelines for that we have a bold plan we have a bold plan looking to get to approval in the latter part of 2030 and we have a bold plan because we like the profile of it and we want to take it out to the community as quickly as possible it's too soon to be giving you the details of our phase three plans we need to keep working those through and obviously discuss them with the agencies but I can tell you how we're thinking about it which is firstly we're very focused on phase three starting 2028 that will be using the entirety of our phase one data on different formulations as well as our phase two data for 184 and 499 for the phase two B's as you heard 184 is underway, 499 we will start soon And then, you know, for the Phase 3s, what I would say is that we're going to learn a great deal from our three times a year treatment trial quattro that we have started. It started mid-26. We're looking to gain approval in 2028. And we will be taking those learnings into the Phase 3 development of our twice yearly. Your last question was on orals. and, you know, there's markets that we're leading in and we just talked about one, long-acting injectables. We know 70% of patients from our market research are saying they prefer a long-acting injectable but we definitely want to cater to those who would rather avoid the injections and we know others have been leading in that space. However, there remains a strong opportunity for a long-acting injection oral weekly that's INSTI based and I've talked about why today in terms of the superior efficacy barrier to resistance and also it's so familiar and highly trusted by patients and providers so we will be focusing on a true best-in-class INSTI based oral weekly and moving at pace we have the H359 which we believe has the potential to be a best-in-class oral weekly captive inhibitor in phase one and we have multiple other INSTIs and capsid inhibitors in pre-clinical developments and I would also say we have a long relationship in INSTI design with our other stakeholders, Shinogi. And so we will update more on timelines regarding your all-weekly interview course.

Great. So we'll do Sean, Sarita and then Session. How about that? So Sean, have you got a microphone up there?

Hi there, Sean Conroy, Shore Capital. Just firstly, I will pick on the one phase three trial in vaccines that you announced of the 34 that you're planning. Is the ambition with this MACE study to ultimately get a labeling change for Shingrix? And could you give us some idea of what that might ultimately mean for progressing the pricing over time? And then maybe for you, Julie, In terms of this restructuring program and this steer of capital into specialty medicines, is there a risk, you know, you've talked about this being for mature products, so presumably the bulk of this is coming from GenMed. Is there a risk that you end up under-investing in some of these brands and this general medicines becomes diluted to the growth story? And if so, how open would you be to divesting some of these brands in the future?

Right, Tasha? So, Sanjay, and maybe Kaivan feel free to give any colour around some of the signal finding work and just the basic hypothesis there. I mean, I think with MACE, clearly the regulatory pathway is more robust than dementia, and that's why that's being prioritised. But Sanjay, do you want to get into that, and then we'll come to you, Julie.

So the answer is the ambition to get a label is an emphatic yes. So how do we get there? and why are we so confident? So first, I showed you seven studies, real world studies, where what is remarkable about the effect size is it's fairly consistent across these seven studies. So despite all the limitations you have with real world studies, the fact that the signal is so consistent gives us a lot of confidence. Secondly, we have some unique insights into biology that we're exploring that might give a little bit of credibility to the biology and the mechanism of action. so if you take these two things together the confidence that we are going to be successful in this study remains high and that's why we're embarking on this we are in discussion with regulators and the reception so far has been very favorable so we are progressing and hope to finalize those discussions over the next few months to really move forward with the MACE study and as Luke said the pathway and the road map for MACE is relatively well established the end points are fairly standardized and I think Kayvan can can speak to them the way we conduct these studies and the benchmarks are available already. It's much more of a difficult discussion with dementia which is a much more heterogeneous condition and we are in discussions regularly as to trying to solve that.

Just to add that my organisation has significant experience in cardiovascular outcomes trials and so the design that's being implemented for sugar is adequate and well controlled to support a registrational but Sanjay said this is a fairly unique setting where clearly the data in support of Shingrix's cardiovascular benefit appears to be working through inflammatory mechanisms rather than through lipids, blood sugar or blood pressure and so we've done a lot of work to ensure that there's understandable mechanistic plausibility that would go in concert with that large outcomes trial and we've engaged the appropriate experts to make sure that's an integrated package

Can I suggest for George maybe just addressing or overall the impact on the physicians and patients Yeah maybe to talk a little bit more broader about what we think the benefit of such an indication would be just to take a step back when you get an additional indication for a vaccine like Shingrix it's not to get a license for a broader population but to increase the motivation of people to be vaccinated and we've got extensive research that shows that when there is a strong recommendation from a physician, the willingness to be vaccinated increases from 40% to 8%. And we also know from research that an indication such as MACE or dementia for that matter, increasing the confidence of the physician to provide a strong recommendation from 50% to 90%. So that gives you, I think, a very good understanding of what the benefit is of such an indication. But also, it's a major driver in the short and mid-term ahead of such an indication of why we are focusing so much on comorbidities and comorbid patients to be considered for vaccinations for Shingrix. And in fact, more than 70% of the 50 plus population that Cingrix is indicated for are suffering from these comorbidities. Obviously, Sanjay spoke about how this proposition improves the economics and if the study is positive and we have the data, we will be looking obviously at what that means in terms of price. Great, thanks George. Julie.

Yes, okay, the GEMMED question. The GenMed business is a valuable part of our portfolio. A number of reasons for that, but one of them is that it's synergistic with the other part where we sell respiratory. So vaccines, obviously, with Erexi, together with specialties such as Nucar or Accenture. And so there's an ability to use the field force across multiple parts, GenMed vaccines and specialty. The other point about GenMed is that although it's under some degree of pressure, it is significantly a cash-generative business, so it's part of the portfolio overall. Very importantly, the reason we're choosing to invest behind specialty, more so, and it's actually of the seven major assets that have been chosen to be accelerated, specialty is six of them. It's just because of the longevity, the future of that business, and the growth and the profitability from that business as time moves on, as you go out of investment phase, into major launch and thereafter. Oncology in particular, people probably know the margins that you get in oncology products. So that's essentially why.

And we've signed a series of deals in emerging markets across multiple geographies with companies like Zoolink where there's basically revenue targets and profit sharing to obviously put some ballast with that. So I think, Theresa, your hand was up and then session? Yep.

Thanks, Teresa, from Morgan Stanley. So the later stage pipeline appears to be weighted to assets, as you've highlighted, that are de-risked mechanistically and clinically. But how should we think about the commercial risk of entering markets with potentially entrenched competitors? And are the convenience advantages alone, so for example, with aisle 33 wrapped, enough to drive meaningful share? And then just a quick one on NELA and out positive lung front lines. Is it possible to get an earlier look versus 2030? So could it come at interim in 28? And what percentage of the overall value or peak sales opportunity is contingent on front lines?

Thank you. Sure. Okay, so Nina, do you want to cover that? I'll resist adding two cents, my two cents worth, because it's better we hear from the team today, and then we'll go to Hesham.

Just with the last one, is it possible to read out early? Yes, it's possible. It's event-driven, so events will determine how early we get there. In terms of competing with long acting specifically, I think I want to be very specific. Long acting is First thought that comes to mind is it's convenience. It's actually not. It is convenience, but it's a feature of the drug that ends up in better persistence or longer persistence and earlier use. So it's a feature of a drug that changes potentially benefits for patients and the willingness of the physicians to prescribe the drug earlier. So both of those things are translating into patient benefit and outcomes. and I think one core component of success of long-acting formulations is to position it like that and profile it like that rather than just convenience. And then on Mela, I'll... First line is the bulk of the value, as you'd imagine.

But we did an enormous amount of due diligence with physicians who had empirically exposed to the drug and it's recruiting incredibly well. So that's always a good sign. Hesham, anything you want to add?

And maybe just Satya and I are actually talking about this a little bit at the break as well too. Just a few points to highlight. The first of course is as we think about the comparator in the study. Of course, different comparator versus the lower latinum trial. So this is against a second gen TKI, so just something at least to take into account. The second, of course, to Luke's point, recruitment rates are really important in terms of how these event-driven studies actually read out as well, too. And then the third, of course, is how early does that separation actually take place? I mean, when we look at the data with NELA, especially in the TKI-98 patient population, we look at these 12-month duration of response, 91% versus 70% with loralatinib. The response rate, 86% versus 76% as well, too. So I think these are all variables that we have to take into account. But in addition, we're always going to be opportunistic in the context of how the trial is designed and specifically, again, like I said, how early that, you know, at least separation occurs and possibly when certain interim analyses could potentially lead out as well, too.

And I'd just add, just to build out on the commercial differentiation, I mean, you use the example of the RAP transaction. I mean, we had been following Xolair for multiple years, and I can remember back at Roche, this product was expected to be finished, yet it kept growing. And initially, we thought it might have been driven in asthma. Of course, it's not. It's being ablated in that population. Then we identified, Chris's team identified RAPs, and then we started to do market research and talk to physicians using it. And it was pretty clear the barriers there in terms of dosing. the 25% population with obesity etc. and just the frequency of having to treat children in particular. Then we characterised the BTKs and the safety profile of BTKs and it was pretty clear for paediatricians that they would be reluctant to use those drugs in kids. Plus the half-life is pretty short so how much coverage, if they're away, away from supervision etc. So it's always a combination and then you had the target obviously de-risk and the learning from Novartis So it's always a combination of things that we do. So thanks Sarita. Sachin?

Sachin Jain, Bank of America. A few questions please. So firstly on BEPI, I know we've got a bit of time post-ease, or maybe you could just update us on your thoughts as to how you think about the speed of launch. So two deltas, any sense on speed of payer uptake both commercially and in government channels given that government is a big section? and then you've commented to a bolus of patients again I wonder if you've got a better sense of that so you listed today 50,000 patients in the US less than a thousand of that population do you have a sense how many could be fast adopters just to you know so just to sort of start thinking about the cadence of launch as we think about back end of this year early next year on the IL-33 do you have a target exacerbation reduction profile that sort of puts together all of your So internal data, mucus, etc., relative to existing biologics at 20-25%, and it sort of builds on the duration. And then just one follow-on for Hessian, which we didn't get to touch on earlier. It's the first disclosure of 35% of patients recruited in the study, which I know you said it's in line, but given, I don't know, the 300 KOLs or whatever you've spoken to, they're very excited. It seems to me that may be a little bit slower than anticipated, given the study's been running for a year, but just any sense there, and can you accelerate it? Thank you.

Great. Do you want to cover that one first session? Then we'll go to Kaelin on aisle 33, and then we'll do Bethy. And Pedro, feel free to add in anything as well. Pedro's joined us from Adly, has quite a bit of experience in that area.

Thank you, Luke. I'll start off first maybe by saying, of course, that recently at ASCO we just saw the first line TKI naive data for NELA as well, too. And prior to that, I'd probably say the data that had been communicated was probably relatively limited in its scope. So I think we're starting to see now, certainly in terms of recruitment, picking up quite significantly, especially with the communication around the data, the potential of the asset itself. And of course, how we're seeing not only the medicinal chemistry design of the drug itself, but also the pharmacology playing out, especially the fact that it has this activity against both single ALK mutations and compound ALK mutations as well, too. Getting to the question specifically around recruitment. What I would say is no doubt are there opportunities to accelerate it. There is. We're actually engaging and NewValent has been engaging, of course, with patient advocacy groups, certainly investigators. There's a lot of excitement about the drug itself. and I think when you add to it the potential in terms of scale that GSK brings in terms of clinical operations and execution as well, we see a lot of potential for that. I mean, Luke talked about and touched on the fact that Nina as well too, that we're seeing at least with Belzatinib more than 200% ahead of recruitment, our second line study. So we see the same potential here, especially in these areas of high-end need and we think that certainly that could pick up, especially over the next six to 12 months.

Great, thank you. Yes, I think the question was effectively the product profile we'd be targeting with IL-33 and as Nina said, per the entire portfolio, long or ultra-long acting. We don't have to trust our intuition. That's a good thing. Extension is going to qualify and substantiate why that translates to clinical benefits in a real-world setting. With IL-33, we additionally have a mix of mechanistic and trial innovation and so Exacerbation reduction target sizes, we're accustomed to seeing those for T2 elevated disease. In T2 low disease, there's no approved therapies. So the types of reductions we've seen with Nicala, for example, I think would be transformative in T2 agnostic target medicine profiles. But what I would say is that IO3 is very different from the mechanisms we've seen previously. So I wouldn't expect it necessarily to work on spirometry, but you might see an enhanced effect on severe events, hospitalisations, and as I've described, the biology also potentially is having a direct effect that's protective on the vasculature. And so for us, the types of effect sizes you've seen previously, but extending into all types of COPD, additionally in particular for severe events, and the cardiopulmonary hard endpoints I think will materially differentiate our program.

Nina, uptake, bolus?

Yeah, definitely. So on Bepi and then Pedro, please, as Luke mentioned, Pedro has history of working in Hep C, so pretty good idea of where we might go. So bolus, yes, we expect basically that patients who are currently on treatment and you know that these patients are on lifelong treatment are the first patients who will start therapy. When we talk to the physicians and centers that treat heavy patients, they will quote frequently number of patients that they expect they will start in therapy as soon as available. Testing in different geographies is at different stages. So in Asia, testing is very present and part of routine care. As it doesn't determine diagnosis or treatment in the U.S., it's definitely less present. It's a relatively simple test. It's just not used because it doesn't help at the moment in the treatment pathway. We are working on that as well, supporting centers to implement or start having testing available. We have pretty good idea on price where what is going to be acceptable and obviously you will see the price once the drug is approved I think we made the comment before we do expect to be in the scale of Hep C now that has been quite some time ago we will see where we end up pricing then negotiations and specifically enabling access will happen as after the approval so end of 26 and 27 discussions with the with the payers in the US, which we expect to then unlock. In terms of barriers, we do expect the testing will be required for as part of prior authorization. I don't know, Patrick, if there is anything else you want to add.

Yes, to add to that one, that there was like in the ECV space, there was kind of a bolus of patients and that's what everyone has in mind. With VEPI, we are expecting a different approach. We are very pleased with the way the medical society has taken the VWEL data in the functional cure, but also beyond functional cure. But what was driven the ACV uptake was mainly the cirrhotic patients that were waiting to get that cure. Here, the treatment is not on the cirrhotic patients, so we are expecting the patients really to be willing to be treated. Actually, there is a segment, quite sizable segment, that in the market research are coming really willing to start the treatment as soon as possible but that will be basically going to the doctor when they need to go. We are not expecting what happened in ACV that basically there was a massive pressure to the doctor but also to the players to get the product reversed mainly because this erotic status. But we are expecting really a fast uptake in that population that is really willing to be treated.

Great. Yeah.

Medicare, these patients basically are all over the commercial and Medicare so we are expecting Medicare to come a little bit later due to access situation but there is a lot of these patients that are with a commercial.

A relatively high geographical concentration in the US, typically vertical as you'd imagine. Other questions? We'll do two in a row then we'll go online. Michael.

Thank you. Just on HIV, the IP for cabotegravir up to 2040 may be longer. What are you assuming in your revenue estimates? So when we look at your indicative revenue chart, what's in those assumptions? And then just maybe Kevin or Nina, back to IL-33. If I heard it right, you're going to do the carbon metabolic endpoint with a partner, I think you said academic. Is that not going to slow you down, given that this is going to be a competitive space?

Do you want to go with that one first, and then we'll come to Julie and Deborah on the assumptions?

Yeah, to be clear, it's not an academic alliance, it's with a professional ARO, which are the organisations responsible for running most cardiovascular outcomes trials. So the opposite, we're going to be partnering with An established entity that has delivered multiple MACE-like studies over the last 20 years. You can imagine there's a list of them that are familiar in the Boston area and beyond.

And maybe just to clarify, that's not the only outcome we will look at. So if that's your question about slowing us down, we will have the standard...

and you're right, it won't be dramatically shifted, exacerbation studies and this type of cardiopulmonary composite endpoints, it might be that study's a year later than the exacerbation study, which obviously we would file off the exacerbation study if it came sooner.

Logically, we're trying to aggressively exploit differentiation and disrupt, you know, the targets being de-risked for us. Okay, Julie and then Deborah, and then we'll take one online. Yeah.

So in terms of cabotegravir, the new chemical entity, patent protection is into 2031. Obviously three year patents, three times a year patents are then pending and they would take you into the mid 2040s. I mean just in the way in terms of how we take these things into our forecasts. until we get an extension or until we get a new combination we would always in the forecast we do we would use the the earlier date of expiry until we have extensions available to us etc. Debra?

Yeah so just to build a little bit on how we're thinking about this so we've got patterns granted for the six times yearly so current Cavanuva to 2040 and we've got a number pending so there is a robust intellectual property strategy that's playing out the other way I think about it is how quickly can we cannibalize one product into another so it took us 12 months to cannibalize the once monthly into twice monthly about 70 percent in the first year and then everything else pretty rapidly afterwards our expectation is that we would rapidly cannibalize the six times yearly into the three times yearly and obviously that's coming in 2028 and then we would rapidly cannibalize a big chunk of the three times yearly into the two times yearly because in treatment there is a really strong value proposition for the twice yearly because of the unique assets vh184 and 499 in the way that Charlotte's described so in our model we are modelling a very rapid cannibalisation in treatment product by product as you get further and further through the pipeline PrEP is a little bit different it's a much smaller opportunity for us market size wise but also we absolutely prioritise treatment so in PrEP I think you will find a coexistence of the three times yearly and the two times yearly because some physicians really as Charlotte described really want that three times yearly they want people to come in and have their sexual health dialogue rather than just leaving people unprotected for too long. So I think it's the way of thinking about it would be IP and cannibalisation and as you bring it together, the pipeline really is very, very sustainable from a value perspective.

Thanks Deborah. Okay, last question is a fine one. Oh, we've got three on fine. Okay. Three people with three questions? Okay, three people. All right, well, who's up?

Our next question comes from Seamus Fernandez at Guggenheim. Please go ahead.

Hi, Seamus. Hi, everybody. Thanks for taking my question. So I wanted to ask a little bit more about the accelerated approach on the respiratory side, particularly with the long-acting TSLP It says on clinicaltrials.gov right now that there is an ongoing kind of formulation study, but you are planning to move forward in the second half of this year. I just wanted to get a little bit more color on your confidence that this formulation will have true kind of full six-month coverage all the way through the sort of end of treatment. And then the second question is just your conviction in the TSLP mechanism having a robust result in COPD. I think that's one where I think there's still some questions and whether or not TSLP should be targeted to patients with elevated eosinophils. Thanks so much.

Great. Thanks, Jameson. I mean I would start the answer and then we'll go to Kevin. We looked at every long-acting T-slip out there and this was one that we clearly had the most confidence in in terms of its durability. Programs and context Kevin?

Yes, so very confident indeed because we've run a phase two study. We now have interim pharmacodynamic data that supports the Q6M profile in asthma and as I said earlier we also have data in nasal polyps from our partner Hungry which has allowed us to have Confident discussions with regulatory authorities for end of phase two. We've actually now submitted all three phase three indications under the IND and we will be starting those six studies by the end of the year. So very confident in terms of our ability to select those confidently across all three indications which I think is unique in the ultra long acting space for TSLP. Mechanism wise, I think that the data we saw with TESPIRE demonstrates a best in disease profile for nasal polyps. In asthma, clearly the differentiator is that it's truly eosinophil agnostic in asthma. But you're right, in COPD we don't expect it to work in true T2 low disease in contrast to what I described for IL-33. So the COPD study will enrich based on either eosinophils, phenol or a combination thereof so that we're in that sort of intermediate high T2 space.

Right, next question.

Our next question comes from Carrie Holford at Barenburg. Please go ahead.

Hi Carrie. Hi, thank you for taking my question and thank you for the full The one thing that stood out to me, I think, is very clear. Business development is increasingly central to your pipeline. And the commentary today suggests it will remain so going forward. So really my question is, following the failure of Camerapixel that we saw recently, are there any key learnings that you can now take from the Bellis acquisition? Anything you would highlight here, particularly in the context of you know more recent business development decision making post that deal with Bellas and you're thinking about your recent round of BD but also your decision making when you are looking at future targets going forwards.

Great thanks very much I mean I think and feel free to add guys or Tony as well and I think with Bellas Again, we approached it, we tried to integrate the lessons from Jeff Apixson in terms of target selectivity, dysgousia, taste disturbance, the cough counter, all of these elements and in the end we had one study that worked and one that didn't. But then we looked at the totality of the data, we just thought okay, this is not going to shift care and so we took that decision to reallocate the resources. I'm not sure what else we could have done different. I mean, in the effect, the effect was disrupted by a Hawthorne effect. You know, obviously people changing their behaviour when observed. And that's always a challenge. We knew that was a challenge in that program. So I'm not sure it would drive a main shift, but you are correct. I mean, we are very committed to BD. We're very active. With BD, we see it as an integral part of the strategy. But again, disciplined and the deals that you've seen us done this year already, I think are a good framework to employ for the types of transactions that we would be looking to execute in the future. And at the end of the day, this is drug development. You have a portfolio for a reason, typically phase three programs, 75% probability. So you are going to have situations like we had. I don't know, Tony, you want to add anything else?

Just to re-deposit, hi Kerry by the way. Look, for Canlipixen, we took it on because we saw a significant unmet need in an area of adjacency. If we learn anything from it, and you can now see it entirely reflected in the portfolio that you've seen this afternoon, which is where we can, we're focusing on hard endpoints. You heard that in the MACE versus dementia conversation that was going on around Shingwick. as well. But again, I mean, let me just reinforce, this is an area that we saw was an adjacency for us. It had high unmet need. Obviously, we're disappointed, and particularly disappointed with the patients with refractory chronic cough. They have no medications. The study read out in the three dimensions that we were anticipating, the Hawthorne effect overwhelmed the outcome to a greater extent than we anticipated. Thanks. Thanks, Kerry.

Was that your only question? Well, if I can squeeze another quick one in.

As I've been online throughout, I promise.

HIV, I wonder if you can just talk briefly to how aptitude is faring in that PrEP market. I know you referenced it being less important than the treatment, but how is that faring in PrEP relative to Gilead? And what do you expect for market share evolution in that space? if Merck succeeds with a once-monthly pill. Thank you.

Great. Thanks, Kerry. So, Deborah, over to you.

Thanks, Kerry. So, I think what you're seeing is a reshaping of the PrEP market. It's continuing to grow rapidly, and as more options come in, less optimal daily treatments are being replaced by longer-acting ones. And I think the Merck once-monthly Our own long-acting injectables and obviously our competitor long-acting injectables are all going to serve patients and protect them from acquiring HIV in a way that the daily orals had not done because people just did not adhere to them in the way that they needed to. So I think that it's a really good story for innovation. In terms of what's happening at the moment, so you will have seen that we grew Apertude 39%. The market continues to grow. We're holding share in a fast-growing market, and you will see years to go has had a relatively good uptake. Long-acting injectables are growing fast in the segment, but I think we're holding our own, and I'm really delighted that versus our competitor, we're holding our own, and we're continuing to grow in this part of the HIV market. but as I say, more choice is good when what's there today is suboptimal. That's why only 25% of people who could benefit from PrEP are currently taking a PrEP. So I think it's going to be a good news story for those that are involved in that market.

Great. We'll take one more question and then I think we'll close because it's very sunny outside.

Our final question comes from Steve Scala at TD Cohen. Please go ahead.

Thank you very much and I have two questions. First, Given that GSK seems to be an industry leader in organizing decades of in-house data, why was the term AI spoken I think only twice today and certainly wasn't a focus? And then secondly, I'm curious, why is enlarging R&D presence in a country that is so difficult on pharma and you might not launch new drugs, some new drugs in the future anyway, Why is that a good idea? As one example, GSK employees won't even have access to the latest innovation. Is there some aspect that we're not seeing? I think you'll answer that the talent is so rich in Cambridge, but there's certainly other parts of the world where that's the case as well. Thank you.

Thanks, Steve. So, I mean, on the AI one, my rule of thumb is the more people talk about it, the less they're doing. So we are very, very active. But again, I think we're quite selective in terms of what we disclose because I think it is so fluid right now. And these people are very difficult to attract and retain. We're quite cautious about how much we disclose, but clearly the effort we're putting is really on the frontier of Tony's organisation. I mean, do you want to provide a little bit of colour and then I think, Steve, your second question is very fair and you will hear the answer from Tony exactly as you've just said. I suggested it might be, but I'll let Tony answer and then we'll close.

So look, AI is at the center of everything we do. We don't talk about it so much because of what we feel is a competitive position. It's pointless without data. So we focus very heavily on the acquisition of data and that really underpins the approach that we've taken. I'll tell you more about it, Steve, when we talk about early R&D and how we're applying AI, not just the idea of matching targets and patients and opportunity, but designing molecules and ultimately making clinical trial execution more effective. We've got 150 people in our AI group. These folks have PhDs in math. We don't unwrap other people's shrink-wrapped AI products. We have access to token windows through our collaborations with Cerebras, for example, that leave us stable. for the coming two to three years where GPU utilization is going to be a really big question. But I'm keeping what we do pretty close to my chest. We'll share more of it. But as I say, it's all about the data. And in fact, indeed, Steve, I don't want you to misinterpret. We are continuing to underpin our presence in the UK. I don't think we said we were increasing it. And again, there again, it's all about a focus on data. The relationships that we have with Cambridge University that I mentioned. We also have relationships with Oxford University and with King's College. And we'll continue to deepen that type of relationship elsewhere in the world as well. I mentioned in the deck that we'll be looking to do more on the east coast of the US. You'll hear more from us on that in the near term and indeed in China. So I'd say what we focus on is where we can access unique patient related data that helps us make the sorts of decisions that you've heard illustrated throughout the afternoon and we apply AIML where it enables those decisions in an effective way based on the nature of the data and the iteration that's available within it.

Great, thanks Tony. So I think we close now. Firstly I wanted to thank you all for participating again very thoughtful and fair and challenging questions so I appreciate that. Thank you to the IR team. Well, firstly, thank you to the presenters. I mean, yeah, I personally couldn't be more proud, and there's a massive amount of thought and effort that's gone into this, and it's a privilege on my part, frankly, to moderate this today. For the IR teams, thank you. It is a huge amount of work, particularly to Joanna, who had to pull all these slides together, and also the LSE group and the CONS group. India has been coordinating it, and everyone else that helped out. So thank you. Concludes it. If you're in the room and you would like a drink, we're serving-