GSK plc American Depositary Shares (Each representing two Ordinary Shares)

Hello, everyone. Welcome to today's call and webcast. The presentation was sent to our distribution list by email today, and you can also find it on gsk.com. Please turn to slide two. This is the usual safe harbor statement. We'll comment on our performance using constant exchange rates or CR unless stated otherwise. Please turn to slide three. Today's call will last approximately one hour, with the presentation taking around 35 minutes and the remaining time for your questions. Today, our speakers are Emma Walmsley, Tony Wood, Luke Miles, Deborah Waterhouse and Julie Brown, with David Redfern joining for Q&A. Please ask one to two questions so that everyone has a chance to participate. Turning to slide four, I will now hand the call over to Emma.

Welcome to everyone joining us today. Please turn to the next slide. I am delighted to report that GSK's momentum this year continues with excellent second quarter performance. Sales grew 13% to 7.9 billion pounds, core operating profit was up 21% to two and a half billion pounds, and core earnings per share rose 17% to 43.4 pence, all excluding COVID solutions. This reflects our continued focus on operational execution and the strength of GSK's broad portfolio to prevent and treat disease. Sales growth was reported across all three product areas for the first half. For the second quarter, vaccine growth was driven by international expansion. Specialty medicines in particular were up strongly, growing over 20%, reflecting successful new launches of Jara in myelofibrosis, Gemperli in endometrial cancer, and long-acting HIV treatments. and we also delivered a record quarter for Trilogy in general medicines. All of this demonstrates the strength and breadth of our portfolio to deliver competitive and profitable long-term growth. This strong sales performance has been underpinned by effective cost control, driving operating leverage and further margin improvements this year. And these benefits are also delivering improved operational cash flow, providing funds for pipeline investment, as well as returns to shareholders. Our dividend for the quarter was 15 pence. And on the basis of our current performance and prospects, we are again upgrading our full year guidance. Next slide, please. We continue to invest in the pipeline and are making good progress. This quarter, GSK's longstanding expertise and leadership in respiratory will once again reinforce with positive phase three data reported for Depimocumab. In oncology, we continue to progress material growth opportunities, most notably the presentation of positive second line combination data for Blenrep to treat multiple myeloma. In vaccines, EREXV was first again with the approval by the FDA to prevent RSV disease in adults aged 50 to 59 who are at increased risk. Although ACIP's postponed vote on recommendation for this cohort was surprising, we have to remember this is a brand new vaccine. We look forward to sharing the additional data requested and more, and remain very confident that the benefit Erexi can offer to this age group, like other cohorts, will be fully recognised and that this best-in-class vaccine will reach its full sales potential. I'm also delighted that we've taken steps forward in clinical development for our pioneering ultra-long-acting HIV medicines, our potential functional cure treatment for Hep B, and our novel antibiotic, Gepatidazole. Next slide, please. Building trust by delivering across the six key areas we've prioritised for ESG remains a clear priority for all of us at GSK. Earlier this month, In partnership with Medicines for Malaria Venture, we launched Afeniquin in Thailand and Brazil. This is the first single dose radical cure medicine to prevent malaria relapse, another step forward to eliminating this disease. In May, we became a founding partner of the Fleming Initiative, a new global network that brings together scientists, policymakers and the public to fight antimicrobial resistance. And we've also started a phase three trial for a low carbon version of our metered dose inhaler, Ventolin. Using a next generation propellant, our new inhaler has the potential to reduce emissions by around 90%, versus the current one, and benefit millions of people with asthma. Please turn to slide eight. So I am delighted with GSK's continued progress and strengthening prospects. But before reminding you of these, a quick word on Zantac, given the ruling we had on admissibility of evidence this quarter. This Dalbert ruling in Delaware does not determine liability, and our position remains unchanged. We will continue to defend against the claims being made, and our aim, as it has been all along, is to manage this in the best interest of the company and shareholders, and to stay focused on our delivery. As many of you know, we started this year by setting out new, upgraded long-term commitments. And we're all focused on delivering against all of these, short, medium, and long-term. With our current momentum and the continued progress we're making, we have today upgraded our outlook for 2024, demonstrating the strength and in-depth and breadth of our portfolio. We now expect to deliver sales growth of 79% and core operating profit growth of 11% to 13%, with a short-term shift in this that the team will comment on. For 2026, we continue to expect more than 7% sales growth and more than 11% core operating profit growth on a five-year CAGR basis. And for 2031, we continue to expect sales of more than £38 billion with a broadly stable margin through the loss of exclusivity of Dolotegravir. And remember, these outlooks do not yet include the launch of Blenrat or ongoing progress in our early stage pipeline. So I'm now going to hand over to Tony to talk you through our R&D progress in more detail.

Thank you, Emma, and welcome, everybody. Next slide, please. As you know, our approach in R&D is to invest for growth in new best in class vaccines and medicines, combining our scientific focus on the immune system with the use of advanced technologies. Today, our pipeline comprises 70 assets in clinical development, and my priority remains the acceleration of the delivery of new vaccines and medicines for patients and to drive future growth for GSK. In the past six months, we secured regulatory approvals or received acceptance of submissions for 10 major medicines and vaccines and reported positive data from seven phase three studies. clearly demonstrating the innovation and health impact that GSK is now bringing to patients. Focused business development has continued as well. We strengthened our respiratory pipeline with the acquisition of Aeolus Bio for their long-acting T-slip antibody anticipated to start Phase 2 in 2025, and we gained full control of our candidate mRNA vaccines by restructuring our collaboration with CureVac. accompanying these were investments in two new technology platforms the acquisition of lc biotechnologies which will help accelerate our oligonucleotide program and an agreement with okra bio that will create foundational liver biology data sets deepening our understanding of disease and improving target identification in all we've advanced the pipeline across all our core therapeutic areas And importantly, we're on track with the development of the 12 scale product opportunities as well as Blenrep that we highlighted at the start of the year. These all have the potential to deliver profitable growth in the 2026 to 31 timeframe and to support our 2031 ambition of more than £38 billion in sales. I'll now take a closer look at a few important areas. Next slide, please. First in vaccines. where preventing seasonal viral and high-risk bacterial diseases remains a key focus for us. We have an extensive development plan for OREXV and continue to see this exceptional vaccine as a major long-term growth opportunity. OREXV is the world's first RSV vaccine and has demonstrated outstanding efficacy in adults of various ages. including more than 94% during the first season for people with comorbidities and who are at increased risk of severe RSV disease. In June, ACIP recommended use of EREXI for all adults aged 75 and over, and for adults aged 60 to 74 who are at increased risk from severe RSV disease. The committee unexpectedly postponed a vote in adults aged 50 to 59, requesting additional data. These include evidence from vaccine surveillance databases to further support the benefit-risk profile observed during clinical trials in a real-world setting. We look forward to contributing to these data over the coming months. I'm also looking forward to the data from studies 006 and 004 assessing efficacy, immunogenicity and safety of orexi over three RSV seasons. These data will be important to help answer some of the questions raised by ACIP on outcomes and duration of protection. As a reminder, Season 2 data showed 75% cumulative vaccine efficacy against severe lower respiratory tract disease over 23.3 months. These data support the strong and durable protection that this uniquely adjuvanted vaccine offers against RSV. Later this year, we're also looking forward to sharing more from trials in adults aged 18 to 49 who are at increased risk from RSV disease. Next slide, please. Next, a comment on the interesting data for Shingrix that we shared yesterday at the Alzheimer's Association International Conference in Philadelphia. These data add to the growing body of evidence exploring the observed association between shingles vaccination and a reduced risk of dementia. Our study was prompted by a number of observations, some of which are summarized on this slide. There's a growing body of evidence largely generated from retrospective case studies in very large populations that herpes zoster vaccination is associated with a reduction in the diagnosis or onset of dementia. These data include a recent observational study in Wales which concluded that vaccination with a live attenuated herpes zoster vaccine was associated with a 20% reduction in dementia diagnosis when compared to people who did not receive the vaccine. Using an AIML approach and data from Optum's electronic health record dataset, we constructed a retrospective observational study comparing matched cohorts of adults vaccinated with Shingrix, a competitor live attenuated shingles vaccine, and a comparator pneumococcal vaccine. Headline data shown on the right-hand side of this slide suggests that after three years, Shingrix was associated with a 27% reduced risk of acquiring dementia when compared with the competitor zoster vaccination, and a 24% reduced risk of dementia when compared to the comparator pneumococcal vaccine. The potential relationship between shingles prevention and risk of neurodegeneration is an area of increasing interest for the scientific community. These are interesting early results, which we are investigating with additional retrospective and mechanistic studies. Next slide, please. Turning now to respiratory. We're making good progress with novel treatments that could provide more effective options for severe asthma, COPD, and refractory chronic cough. Depimocumab is the first ultra-long-acting biologic engineered to have high affinity for IL-5. It enables sustained inhibition of type 2 inflammation with twice the early dosing versus current options, some of which require injections every two weeks. This quarter, we announced that two pivotal phase three trials in severe asthma with an eosinophilic phenotype, Zwift 1 and Zwift 2, met their primary endpoints, demonstrating that two doses of Depamocumab administered over a 12-month period showed a statistically significant and clinically meaningful reduction in significant exacerbations versus placebo in combination with standard of care. We're looking forward to sharing full data at the ERS conference in September, and we remain on track to file the medicine for approval later this year. Depomocumab's development program is being informed by predictive biomarkers and phenotyping, which has enabled us to progress four clinical indications in parallel. The pivotal ANCA1 and 2 trials in one of these, chronic rhinosinusitis with nasal polyps, are now closed for recruitment with data expected later this year. We also expect to see phase three data on the use of Nicala and COPD this year and phase three data for Camlipixent in the treatment of refractory chronic cough in 2025. Next slide, please. You'll shortly hear from Deborah on the important advances in our HIV pipeline. So I'll conclude with a brief summary of the strong progress we've made within the oncology portfolio during the first half. We're building an emerging and high potential portfolio of new medicines. with a growing focus on ADCs, immuno-oncology, and targeted small molecules. For Blenrep, pivotal data from the DREAM-7 and DREAM-8 studies presented at ASCO demonstrate the potential for Blenrep to become the new standard of care for patients with multiple myeloma in the second-line setting. These trials will serve as the basis for regulatory submissions, and we're pleased that EMA recently accepted our first filing for this indication. Additional filings are planned before the end of the year. Also stated the recent mid-management event, we plan to start a phase three trial in the first-line setting in early 2025. For GemPurlie, recent data from the RUBI trial demonstrate a statistically significant overall survival benefit in an all-comer population with primary advanced or recurrent endometrial cancer. GemPurlie is the only immune oncology agent to demonstrate a survival benefit in this patient population. These data have been filed with the FDA and we anticipate a response ahead of the 23rd of August PDUFA date. Carefully targeted Phase 3 trials investigating the use of Gemperli in the treatment of rectal, lung, and head and neck cancers are also ongoing. The first half of 2024 also saw a number of oncology indication trial starts, including GALAXYS301, a Phase 3 trial investigating our TIDGET antibody, Belarustatog, in combination with Gemperli in the treatment of first-line PD-L1 high non-small cell lung cancer. the Gliofocus phase 3 study, which will investigate Zejula in the treatment of newly diagnosed glioblastoma, and a phase 1 study of our B7H4ADC, JSK584, which recently entered the clinic. We're looking forward to seeing more data from our ADCs by the end of the year to inform pathways for accelerated registrations. Finally, we're pleased to announce the recent Japanese approval of Omjara with a line agnostic label for all patients with myelofibrosis. So in summary, a productive first six months to 2024. I'm pleased with the progress we're making to deliver differentiated health impact for people and patients. And I'll now hand over to Luke.

Thanks, Tony. Please turn to the next slide. In Q2, we delivered growth across all our product areas and regions with 7.9 billion pounds of sales, up 13% versus last year, excluding COVID solutions. This includes another strong performance in the US with growth of 17%. Please turn to slide 17. Vaccine sales grew 3% in Q2, excluding COVID solutions. This performance was impacted by short-term factors, and we fully expect the underlying strength of the business to continue over the long term. Globally, Shingrix grew 7% year to date, but was down 4% in the quarter, delivering 832 million pounds. Outside the US, sales grew significantly and represented 64% of Q2 revenue. Shingrix is now launched in 45 markets, the majority with less than 5% penetration, and these markets represent our source of future growth for this vaccine. Q2 growth was driven by a national immunisation program in Australia, expanded European public funding and supply to China. Supply phasing to China is now expected to be delivered evenly across the second half, with 40% of our agreed full year supply delivered to date. In the US, sales decreased by 36% in the quarter due to three factors. The first, channel inventory reductions. And secondly, important changes in retail vaccine prioritisation, in part due to a transition to a new CMS rule effective the 1st of January 24 that changed how pharmacies process reimbursements from payers. These two short-term effects are not expected to repeat in the second half of this year. And thirdly, lower demand driven by challenges activating harder to reach consumers. Addressing this remains a priority with cumulative penetration of people aged 50 and older reaching 37%, up six points since the same time in 23, based on latest census data. With more than 70 million adults that are still unvaccinated and recommended to receive our vaccine, we're focusing our resources and marketing content on targeting these eligible potential patients. Our expectation continues to be that Shingritz Global Sales will grow this year and reach more than 4 billion pounds by 2026, driven by growth outside the US. Turning to RSV, nearly 8 million people have been vaccinated with OREXV since launch, and we're maintaining around two thirds of the retail vaccination share. As expected, demand levels were lower in Q2 due to seasonality. Ahead of the 2024-25 RSV season, We're well positioned in our contracting and still expect blockbuster level sales in 2024. These sales are expected to be second half weighted with the vast majority in the US. And following the recent ASIP recommendation, we received a universal recommendation in 75 plus year olds, but now expect minimal sales in the 50 to 59 age group this year with further potential impact in those age 60 to 74 years. Preparation for launches in Europe and international are underway for 2025 and beyond. With a best in class data profile, we're confident EREXV will return to growth next year and longer term can achieve more than 3 billion pounds in peak year sales. In meningitis, Q2 sales for Bexera and Menveo were up 23% and 30% respectively. Bexera continues to demonstrate strong growth benefiting from favorable pricing in the US, recommendation in Germany, and increased demand from Australian immunisation programs. Menveo grew due to favourable delivery timing in international markets and US CDC purchasing patterns, including our candidate MenAV.CWY vaccine. Our meningitis portfolio is expected to deliver around 2 billion in peak year sales. Given the first half performance and our latest expectations with a tough comparator for orexiv and US Shingrix in the second half, we now anticipate vaccine sales in the full year to increase by low to mid single digit percent. Our increased 2026 CAGR outlook for vaccines of low double digits has not changed. Next slide, please. In specialty medicines, including HIV, which Deborah will cover next, we had a very strong quarter and increased sales by 22 percent, excluding COVID solutions. and our expectations for the year, I'm pleased to say, have increased. New Cala was up 17%, driven by higher patient demand for treatments addressing eosinophilic-led disease, market expansion, and increased biopenetration. Ben Lister was up 20% in the quarter, driven by biopenetration growth from early intervention in SLE and lupus nephritis. We're also seeing growing demand in the US and continued consecutive double-digit growth outside the US. In oncology, sales again more than doubled in the quarter. In haematology, we're continuing to see a strong update for Ajara, which launched in the US last year, and in the UK and Germany in Q1. In gynaecological cancers, continued momentum was primarily driven by sales in the US, Germany, France and the UK in the first line DMMR, MSI high, primary advanced or recurrent endometrial cancer. In addition to growth from second line and later treatment, GenPurlie is the backbone of our immuno-oncology development and pending regulatory decisions and development beyond DMMR-driven tumors, which will drive future growth. So dualist growth continued in Q2, driven by the US, and volume growth globally. And as a reminder, for the next quarter, we will not benefit from the stocking of or the switch to the new tablet formulation as seen in Q3 23. Given the 21% sales growth in the first half, we're increasing our four year expectations, and we now expect specialty medicines to grow mid to high teen percent, with the second half growth being lower due to tougher comparisons in oncology. Please turn to slide 19. Focusing on Nucala for a moment, the chart on the left of this slide demonstrates Nucala's continued leadership in IL-5 market share. And pleased to say that Nucala continues to grow by double digits quarter on quarter, despite being on the market for almost nine years. We anticipate our IL-5 portfolio comprising Depomocumab and Nucala to deliver more than 4 billion pounds in peak year sales. Next, looking at OJARA, we're still seeing the fastest US launch uptake in value for a JAK inhibitor and myelofibrosis. It's the only treatment to demonstrate clinical and durable benefit on spleen response, symptoms and anemia for myelofibrosis patients with anemia. We're finding anemia burden to be increasingly at the forefront of treatment decisions. We continue to improve our market share. 65% of US and EU healthcare professionals expect to increase prescribing OJARA in the next six months. Please turn to slide 20. Finally, general medicines grew by 12% in Q2, reflecting a record quarter for Trilogy, with sales increasing 41% to £842 million. Around half the growth was driven by channel and segment mix, as well as adjustments to returns and rebates, which we expected to moderate in half too. Trilogy also benefited from share gains and remains the top selling brand in asthma and COPD. and is the most prescribed single inhaler triple therapy worldwide. Removal of the AMCAP on Medicaid drug prices in the US had expected to impact branded versions of Advair, Flovent and Lamictal. However, increased use of authorised generic versions of Advair and Flovent offsets this impact in the quarter. Given the strong start to the year, we now expect general medicine sales to increase low to mid single digit percent for the full year. I'll now hand over to Deborah to cover HIV.

Thank you, Luke. Next slide, please. We're pleased to see continued strong performance and sustained double digit growth in Q2, delivering 13% revenue growth. Our growth is driven by continued strong patient demand for our industry leading medicines which has led to an increase of two percentage points in global market share versus Q2 2023. Our oral-to-drug regimens and long-acting injectables continue to transform the HIV marketplace. Devato delivered sales of £551 million in the quarter. The strong body of clinical data and real-world evidence reinforcing the efficacy and durability of this medicine continues to grow. At the International AIDS Conference last week, Results of the Paso Doble study, a large head-to-head randomized clinical trial of Devato compared against the three-drug regimen Victavi, showed non-inferior efficacy and significantly less weight gain. This is important because we know people living with HIV are concerned about taking more medicines as they age, as well as the long-term risk of metabolic diseases that can come with weight gain. Our long-acting portfolio also continues to perform strongly, delivering more than 50% of total HIV growth. Cabinuva grew 42%, driven by patient preference and proven and durable efficacy. Cares and latitude data presented at CROI and data from real world cohorts that include over 10,000 people living with HIV in diverse settings has resonated strongly with physicians and has supported increased breadth and depth of prescribing. Aperture grew more than 100% in the quarter. This medicine has demonstrated proven superior efficacy compared with daily orals and a positive safety profile and high patient preference. As a reminder, the registrational HPTN084 study of PrEP in women was the first to show zero infections in participants who received injections as described per protocol. We believe that long-acting therapies are the future of HIV care, empowering people impacted by HIV with choice and addressing the barriers standing in the way of reaching the end of the HIV epidemic. Looking at the long-acting market, we can see that the treatment market is currently approximately 10 times larger than the PrEP market at about £20 billion, which will have a significant impact on the sales potential for long-acting options. In the long-acting injectable treatment setting, there are no competitor launches planned before 2028. We continue to see strong progress across our pipeline. At the AIDS Congress, we shared first-time in human data for our third-generation integrase inhibitor, VH184, demonstrating strong efficacy and a unique resistance profile. Building on our strong legacy of developing powerful integrase inhibitors, these positive findings reinforce that integrase inhibitors will remain the gold standard in HIV, trusted for their efficacy, long-term tolerability, and high barrier to resistance, and make VH184 an excellent candidate for further development for both ultra-long-acting and self-administered therapies. In PrEP, we've committed to move forward with our registrational studies for cabotegravir ultralong-acting Q4M with confidence in the efficacy and safety profile. In treatment, we've selected ropivirine as the partner for cabotegravir ultralong-acting Q4M. This regimen selection is based on progress in formulation studies for ropivirine and builds on existing positive patient and physician experience with these medicines in our current portfolio. We remain on track to deliver the first ultra-long-acting four-monthly treatment regimen in 2027 and four monthly dosing options for prevention in 2026. We continue to progress our ambition of extending the dosing interval of our long-acting regimens to enable every six months dosing towards the end of the decade. Our strong performance over the first half gives us confidence to increase our guidance to low double digits percentage growth in 2024. With that, I will hand to Julie.

Thank you, Deborah, and good afternoon, everyone. Next slide, please. Starting with the income statement for the second quarter with growth rates stated in CER, sales increased 13%, as Emma mentioned. reflecting continued strong business performance, particularly within oncology, HIV, and trilogy within general medicines. Core operating profit grew 21% excluding COVID and 18% overall. Operating profit grew ahead of sales as we continue to focus on disciplined resource deployment and delivery of a competitive P&L. Core EPS grew 17% excluding COVID. Turning to the total results, operating profit decreased 22% to £1.6 billion, predominantly reflecting charges arising from the CCLs, primarily due to improved longer term prospects of our HIV business and less favourable foreign currency movements. Next slide, please. Moving to the core operating margin. This increased 190 basis points to 31.9% year on year, excluding COVID. This reflected cost discipline, the drive for productivity improvements and targeting resources to the key commercial and R&D assets in the business. In addition, the gross margin benefited from positive regional mix. These factors were partly offset by the impact of the loss of Gardasil royalties as guided. In the first half, we saw a significant margin improvement of 380 basis points at CER to 32.5%, with strong operating leverage underpinned by 13% sales growth, gross margin mixed benefits, and a one-off favorable impact relating to the Zezula royalty dispute. Next slide, please. Cash generated from operations in the first half was 2.8 billion pounds, representing an improvement of 0.9 of a billion versus half one last year. This was primarily driven by core operating profit growth and favourable working capital, with the latter benefiting from higher receivable collections. Free cash flow was 0.6 of a billion pounds relative to an outflow last year, and therefore improving year on year by almost a billion pounds. As usual, we expect to generate the majority of our free cash flow in the second half of the year, given the seasonality of the vaccine business. Next slide, please. Slide 26 shares our net debt position since the 31st of December and how we've actively deployed capital in the business in line with our capital allocation framework. Net debt was 1.1 billion lower compared to the end of 2023 at 14 billion pounds. and this included the monetisation of our remaining stake in Halion. We have a strong balance sheet to support continued investment in future growth, including business development, as we look to deploy funds to enhance growth and deliver attractive shareholder returns. And now with that, I'll turn to our latest full year expectations. Next slide, please. Given our strong start to the year and continued momentum, we are pleased to upgrade our 2024 guidance today. You heard Luke and Deborah refer to our updated product guidance, and in summary, the strong upgrades to specialty care and general medicines more than offset our lower expectations for vaccines this year. In aggregate, for full year 2024, we now expect group sales to increase between 7% and 9%, and core operating profit to increase between 11% and 13%, notwithstanding the loss of Gardasil royalties, which will reduce profit growth this year by six percentage points. Turning to the P&L, the gross margin has been strong in the first half. In the second half, we expect to incur costs to drive future supply chain efficiencies, as well as lower positive mixed benefits given the phasing of the launches last year. In addition, we continue to expect SG&A to grow at a low single-digit percentage, and we now expect R&D spend to increase slightly below sales growth and royalties for the year to be around £600 million. Core EPS is expected to grow 10% to 12% due to an increase in the tax rate under OECD legislation. I am confident in our underlying business momentum, but obviously the second half growth rates are very different from the first, with the second half significantly impacted by the very strong launches of EREXV and in oncology last year, as well as the initial stock builds. In addition, Gardasil was stronger in half two last year, which will impact our profit growth in this upcoming second half. In summary, we are pleased with our first half performance and confident in achieving our upgraded full year guidance, as well as all of our medium and longer term outlooks. Next slide, please. Turning to our IR roadmap, which shares our progress towards major milestones and value unlock opportunities. As you can see, we have made good progress in the first half. In the second half, there are a number of major milestones expected, notably in respiratory. First, the presentation of the detailed SWIFT1 and SWIFT2 data at the ERS Congress for Depimocumab in the treatment of severe asthma in patients with an eosinophilic phenotype. Second, the phase three data readout of Depimocumab for chronic rhinosinusitis with nasal polyps. And finally, the phase three data for Nucala and COPD. We also look forward to our next Meet the Management event at the end of the year, which will be the first introduction to our early stage pipeline. And with that, I will hand back to Emma to conclude.

Thanks Julie. So to summarise, GSK continues to deliver on its commitments and perform to a new standard. Our excellent performance in Q2 underpins the strong momentum across the business. We're pleased to be upgrading guidance and expect 2024 to be another meaningful year of growth in sales, profit and earnings as we continue to focus on prevention and changing the course of disease for millions of people. We're confident in delivering our growth commitments and we continue to progress with development of meaningful innovation in our core therapy areas. Our strong momentum underscores our confidence to sustain profitable growth through this decade deliver scale health impact and attractive returns for shareholders, combining science, technology, and the talented GSK people to get ahead of disease together. With that, I'll now open up the call for the Q&A with the team.

Thanks, Emma. I'm going to take our first question from Peter of Adults at Citi. Peter, you should be enabled to speak, so over to you, please.

Yeah, thanks. Pete from Adult City. Two questions, please. Just firstly for Emma and Luke, I'm sure you're going to get a lot of questions on this, but let's just head it straight off. In light of the vaccine dynamics that you are calling out today and yesterday's comments from Pfizer and Merck, can I just push you a little more on firstly what you're seeing in China? when you think realistically you can return U.S. Shingrix to growth? I realize that's sort of a difficult question to answer, but I'll try. And then lastly, how are you feeling about the contracting for 2024 U.S. RSV in both the retail and non-retail channels? And then a very different and quick question for Tony, just can you remind us why GSK still has enthusiasm for the TIGIT mechanism in light of disappointing compared to datasets. Is there any differentiation that you want to call out on EOS 448? Thank you.

Thanks very much, Peter. Well, let's go to Luke on all three of those. I just would refer you back to his introduction earlier today. The update has shown some short-term impacts on our vaccines portfolio, but we remain very confident in our medium-term outlooks and the strength of our products today and their prospects, as well as the pipeline that continues to develop in vaccines. But Luke, both on... China, US, Shingrix, and I know great confidence in the contracting for the season.

Thanks, Peter. And I suspect you're not Robinson Crusoe with these questions. So I'll spend a bit of time on it. I mean, firstly, on contracting, very happy. Based on what we can see, we will retain market leadership. We're on track to be a blockbuster. We can cover ASIP a little bit later on. But yeah, I think we're very happy with the work that's been done by the team on the ground there. In terms of vaccines in China, look, I mean, I think at a macro level, we're extremely happy with the partnership that we've started with GFA. This is a strategic partnership. This is a long-term partnership. The startup process for Shingrix has been completed in Q1. We have reps on the ground as of the end of May. And if you just look at numbers, they've already expanded from 6,000 points of vaccination that we were covering. They've already hit 19,000 and are on track for around 27,000 by the end of the year. So the scale of that company and the impact that they can bring for workers for Shingrix in China is clear. Now, in terms of broader vaccine demand, we did see some softness in Cervarix, but it's confounded by the fact that we moved resources off the product as well. We do hear some signs that some of the local CDC do have tighter budgets, and this is something we're going to watch very, very closely. But for us, you know, the key here is that Shingrix is a very different point in the life cycle to HPV vaccines. We're just getting started here. So we've got the best possible partner. We'll build the opportunity. If you look at the opportunity, it's very similar to the US when you look at people in China that can pay out of pocket and that are in key cities. So the numbers are very large, but we need to build that. We've just shipped the 60% of the remaining. We'll ship the rest of the order. In the second half, we did have a delay of shipment, not demand-based, but we just booked another 94 million in July. So we're on track to fill the full contract for the year. So that's China. If we get on to the US and Shingrick's growth, I mean, basically for the full year in Shingrix, we're not going to grow versus last year, but the second half obviously is going to be stronger than the first half. If I just expand on the three factors and the first two, let me be really clear. These are half one dynamics. So we've moved through them. The first one is wholesaler, as I said in my earlier comments. That delta is about 300,000 doses. So we finished quarter four, 23 with 700,000 in wholesaler. And that's typically what we like, as I've said on previous calls. In Q2, it went down to around 400,000. So that's something that we expect to be rebuilt as we go into the flu season. The second factor was CMS rule changes covering direct and indirect remunerations or DIR fees. And just as background, these are basically discounts pharmacies pay to Medicare PBMs and plan sponsors if certain quality measures are not met. And the complication has been historically that the PBMs can request these retroactively for up to six months from the point of sale. So that's obviously a complication for the pharmacy and the pharmacy group. The new rule that was brought in removed the retroactive part. So basically at the point of sale, all of these components had to be booked and visible. And what that meant was for the six months, so from January to June, there was just less incentives for pharmacies to vaccinate. and we saw them shifting volumes between different types of vaccines to offset that. We've now moved into the second half of the year. We look at market research, tracking, et cetera. TRX trends adjusting for 4th of July is looking very encouraging. The key thing also, this is very much a pharmacy structural element that has expired. If we look at market research for physicians and their enthusiasm to recommend Shingrix either strongly or extremely strongly, If you're looking at 65 plus, it's 88%. So that's the same as last year. 60 to 64 is 80%. So again, same as last year, 50 to 59 is around 50%. So that's all where it was. If we look at patient engagement, that's also holding overall, but that leads to the third factor. And this is something I've mentioned on previous calls. As we penetrate this population, And if you look at the rate that we've penetrated with Shingrix, it's double the rate of PCV. So we've got there in seven years what it took PCV vaccines to get there in 14. But as I said before, the most motivated people obviously sought out the vaccine and we've been able to penetrate those populations to a very high degree. In our number one segment, we're around 66% penetration. So we have to work harder to get less engaged people, less motivated people. There is a huge plan to do that. So, we will be looking at, you know, patients which are resident in other specialties. We're looking at co-ed, we're looking at co-morbid, ways that we can stop leakage, some account management work that we're doing as well. And then we're just really changing our marketing mix to focus on segments who, you know, are tougher to activate. So... That's the plan. And if you put all this together, basically we'll expect some growth in half too. But, again, we're at this evolution of really looking outside the US to Europe, Japan, Australia, China for our growth. And then ultimately once we've moved through those cohorts, we'll get to emerging markets as we've covered on previous calls. Long story short, we can navigate this and we remain confident that we can hit our $4 billion target. target with Shingrix in 2026. So a long answer, but hopefully that is helpful to everyone.

Great. Thanks very much, Lou. And, you know, I really want to reiterate that confidence in the broader vaccines portfolio and the maintenance of our 26 CAGRs and excitement for the pipeline ahead. But we do see the growth coming ex-US on Shingrix, but the decline in the US to moderate. And I would just point out, per Luke's presentation, that in the US, we absorbed that 36% decline on Shingrix and delivered, whilst digesting that, 17% growth in our largest country in the world. So Tony and Tidget.

Yeah, thanks for the question, Peter. Your quick answer might get a slight, sorry, your quick question might get a slightly longer answer if you'll forgive me. And just to remind you, we've said, you know, our focus in oncology is very much on hematological and gynecological cancers. And we said we'll invest outside of that in a gated way when we see data that suggests transformational opportunities. So with that in mind, what have we seen? What are we doing about it? And why do we think it's happening? So what have we seen? In our Galaxy's 201 platform study, and this is with 120 patients, so a larger patient population than the initial data from the Cityscape evaluation of similar mechanisms, what we see is similar overall response rates, but a speed and quality that is differentiated from those observed previously. You'll hear more about that when we present on these preliminary data at the end of the year. So I'll pause on that at this point. What we're doing with that data now is moving into the Galaxy 301 Phase 3 study. And it's an important... thing to bear in mind about the characteristics of that study um first of all it's in combination with gem pearling we're learning there from what we've um seen in the perla lung study it's also in a carefully biomarker selected population and it is with um eo448 or bellarista for those of you who haven't connected the um The two together, what we expect to see as a consequence of it is as a consequence of a differential profile for EOS 448. It's an IgG1 antibody, which means it has a functional FC region, the constant region of the antibody. That means it engages macrophages, dendritic cells and natural killer cells in the tumor microenvironment, augmenting immunity. And also it induces something called ADCC, which is antibody directed cellular cytotoxicity. And that results in the killing of T regulatory cells, which are immunosuppressive in the tumor environment. We've seen that latter feature of depletion, both preclinically and clinically. So in short, differentiated data moving forward in a gated phase three study and designed based on what we've learned from Perler with a molecule that we think has differential characteristics.

So more to see at the end of the year and a strong focus on gating those decisions. Thanks, Tony. Next question, please.

Okay, so we're going to go to Geoffrey's and take our next question from Peter Welford. Over to you, please.

Hi, thanks for taking the question. I'm sorry, but I want to come back to the vaccines. Can we just come back to EREXV for a minute and just understand, Luke, particularly on the contracting. I understand that you're very confident with the market, the distributors, the share of retail. But the two things, again, firstly, can you just talk about the appetite and what you've heard from contracting distributors? discussions insofar as, I mean, maybe you can talk about the extent of vaccination we've seen in that 75 plus cohort and perhaps the motivation you see in that group for greater incentive year on year, perhaps for those to come in versus on the other hand, you know, the lower obviously age where there was less of a strong recommendation. And equally, if you can just talk a little bit about then the non-retail segment, what you're seeing there, do you see any change to that segment going into the second half of this year? Would you still anticipate that to be a relatively minor part for RSV, given the recommendation that we've seen for 75 plus year olds?

Thanks, Peter. So, Peter, maybe what I'll do is I'll just talk through. I mean, the key thing is we're confident with EREXV in terms of the long-term ambition of $3 billion. And you're right. I mean, the June ACIP was positive for 75 plus. And if you look at our immunisation rate in 2023, of that population, which, you know, our numbers, that's about 26 million. Under shared clinical decision making, we achieved an immunisation rate of around 18% overall. all products. If you look at the 60 to 74 with ACIP, there's no way you can escape that as a negative for the class, right? We have to be realistic there. But there is some lining to the cloud, some silver lining to the cloud when we break that population down. So if you look at 60 to 74 under shared clinical decision making in 23, the immunisation rate was around 13%. Now, the hard part Right now, of course, as we don't know where CDC is going to set the boundaries in terms of what's high risk and complications, you know, is it diabetes or is it advanced diabetes? So it's a bit difficult. But if we just along the lines that you were talking about, if we just look at people with diabetes, other complications in that 60 to 74 group it's a similar number it's about 26 million um and if you if you look at the immunization rate that was under shared clinical decision making for the 60 to 74 population last year was about 16 percent um if you look then a little bit more tightly At the 65 to 74s at increased risk, it was actually high. It was 19.5%. So I assume that's because you're a bit more mobile, you know, easy to reach in the pharmacy versus, you know, care homes, et cetera. So there's clearly in that population there is engagement. And it will just depend on how CDC sets the rules. In contrast, if you look at healthy people, the penetration rates were much lower. So it was around, you know, 11% in the 60 to 74 population and around 15% in the 65 to 74, if you sort of slice it more narrowly. So... Yeah, I think there's going to be more momentum for 75, but you've taken a big chunk of people out in the 60 to 74. And what we don't know is, you know, the reaction of physicians with ACIPS changes, whether they're going to withhold, you know, a recommendation in some populations. So it's difficult to project. Obviously, Q3 is going to be key, and our intention is to maximise your orexia there. We've been very, very deliberate with this product. It has been positioned from day one for high-risk individuals. And then when you look at PCP preference and patient preference, You know, it's clearly the leader in the minds of physicians and patients that are aware of it. And, you know, that makes sense, right? Our data is the strongest. As I said before, it's the one you'd give your mum. And our plan is to go back, feel free to add, Tony, is to go back to ACIP with the 5059 data, with the updated benefit risk safety data and GVS, and also when we've got the full package, the three-year data.

Let me just pick up on one point of that, because I suspect we're going to deal with more questions around ACER. But just to underscore Luke's point in the populations that he detailed, we have a very strong data set, for example, in the 70 to 79-year-olds, that was 94% vaccine efficacy in the first season and 75% across two seasons. see that also with a versus b coverage so we're confident in the strength of our data and our continuing ability to add to that data set as we accrue more and you will and say of course though because i'm sure we'll get more questions around it because anything else you want to add on the retail channel well yes uh yeah i mean you know historically it's around 85 percent um we don't see that as changing and when you look at market research

Why, and we've obviously looked at this a lot, when we saw this change in Shingrix with the IRA removal of the co-pay. And when you look at patients' reasons for going to the pharmacy, from memory, it's like 58% of them cite that the process is easier, that for prefers to do that. There's greater certainty around coverage and out-of-pocket costs. So we think that structure will remain the same. As Tony said, we'll be back in with the 50 to 59. But I think ASIP's going to be very conservative about broader coverage until they've got complete clarity in terms of benefit risk. And I think that's important in the non-retail segment.

Yeah, and it's probably just worthwhile underscoring the 50 to 59 that we see no change in benefit risk proposition for the vaccine relative to season one in that population or indeed in the broader group.

Great, thank you. Next question, please.

Okay, so we're going to go to JP Morgan and James Gordon. So James, over to you, please.

Hello, James Wooden, Jake Morgan. Thanks for taking the questions. I'll stick with the vaccines theme. The first question was just the vaccines guide for 24. So you load it quite significantly today. I think it's about 700 million pounds is the difference. So the question we have, how much of the downgrade is Eurex being lower versus Shingrix? Am I working out right that it looks like the guidance roughly has Eurex being about flat for only the second year in the market or even not growing, maybe even being slightly down? Or have I miscalculated that? And the other question was just orexiv and revaccination. So we saw the two-year revaccination interval antibody-titer data at ACIP. And the ACIP panellist was a bit cautious on the data. And I think I heard a comment now that you're going to share some more data in the coming months. So is that the 004 clinical trial and showing the waning of protection? So are we going to, in the next couple of months, have all the data that relates to whether you can get this two-year revaccination interval? And what is your confidence in getting that now we've seen some more data?

Great. Thanks, James. I'll come to Julie first to give you the building blocks of the guidance of the year. Remembering we are annualising against the launch and then Tony will come to you on data and rebates.

Thanks, Emma. Yes. So in terms of the the overall position with the second half. You probably recall the very strong vaccine performance that we had in half two and the change in the guidance overall to the low to mid single digits is primarily relating to RSV for the reasons Luke mentioned relating to the age groups and the ACIP decision making. As Emma mentioned also, the stocking impact last year was fairly significant. So you'll probably recall that in Q3 we mentioned we got two thirds of the sales were actually stocking going into the channel, together with about 20% towards the end of last year. So there is a very significant first half, second half impact with vaccines. You probably recall our growth rates in vaccines last year were 33% and 34% in Q3 and Q4. So this is the headwind that we face now going into this period. And I think Luke summarised it very well, just in terms of, you know, the exact guidelines in terms of what they actually mean in terms of people at risk of RSV, whether it's a normal diabetic or whether it's one with complications will make a big difference to this second health performance.

Great. Thanks. Thanks, Julie. And just to reiterate that RSV update is purely related to ACEP, nothing competitive. And as Luke said earlier, we'll be looking forward to feedback to great growth in 25 and confident in the long term prospects of this vaccine. Tony, do you want to talk about the data to come, REVAX? Sure.

Yeah, sure. And James, just quickly, 004 is the immuno study, but I want to describe this in the context of the entire data set, since that's really the important aspect with regards to revaccination. We've said we have 006, which is the vaccine efficacy study, 004, the immunogenicity study and other studies, looking at immunogenicity, which we started, for example, in the immunocompromised population. A decision on revaccination will depend on the trends in vaccine efficacy and the ability to boost. That in itself depends on how the various aspects of the immunological profile profile wane over time. I think we talked about this at the last call with regards to our expectations on duration. And at this stage, I'd say rather than making guesses, given that we're only a few months away from the whole data package that we'll be presenting at ACIP, we wait for that and One thing to stress, though, within that, for me, is what we're learning from ACIP is a greater focus on benefit risk and therefore the importance, for example, offered by a longer duration vaccine, both with regards to greater value and benefit risk.

Excellent.

Next question, please. OK, I'm going to take our next question from Richard Parks at BNP Paribas. So, Richard, over to you.

Thanks, Nick. So I've got one on vaccines, one on GenMed. On GenMed, obviously the performance has been strong. I know that's partly driven by strong trilogy demand, but also better navigation of the amp cap removal. So can you just talk about how much of that performance is sustainable into 2025 versus turning to a headwind? And I'm thinking about things like stocking for authorised generics, etc. So just thinking about genmed performance into 2025 then secondly um just to push on rx for a little bit more could you help us just understand how much true visibility you've got on likely second half demand based on the contracting and i'm i'm just trying to compare it to maybe the flu vaccine market where generally it feels like people have got good visibility there and obviously with the asip panel recommendation happening only recently it might take some time for retailers to digest that and predict the demand. And obviously, that could work both ways, either additional orders for you and upside or downside through return. So could you just talk about your visibility and where the risks lie, either to the upside or downside for RXV and guidance? Thanks.

All right, well, two more questions for Lou, although we will guide on 25 in 25, and there's no change to our mid-term CAGRs for GenMed. It's obviously a great performance there. So do you want to start with that, Lou?

Yeah, and thanks, Richard. Look, I think a lot of it is really one-off effects of authorized generics, and I'm pleased to say that we were more successful than we were expecting in terms of being able to capture those patients as they came off Adver and FlowMed. With Lumicto, we just took a price hit, and that was very sizable when we did that because we didn't want to disrupt those patients. So, you know, the underlying growth is lower overall. And it's very much along the language we used in the past for general medicines over the longer term. I mean, trilogy itself continues to grow very strongly, but of course it did that outside the US as well. I mean, Japan was up 29%, China 26, and the EU was up 15. So, you know, this is an excellent medicine. It's one that we're going to continue to back. We had 10 recent presentations, publications. So there's a lot of momentum there, but yeah, that, Again, we'll start to lap those components of shifting and the movement with authorised generics in the second half of this year and 2025. I won't comment on. In terms of clarity, I mean, the key difference structurally is with flu, we do a lot of pre-booking because there's a manufacturing cycle. It's a new product every year. It's definitely softer this year. If we look at flu volumes, they were higher than normal in the first half of 2020. in the US, but Southern Hemisphere was weak. So it's not a really good surrogate with EREXI where, you know, we don't have guaranteed volumes. We've got guaranteed percentage splits, which I won't go into, and that's why I'm quite happy about where we've landed. And I think the other factor is pricing. You've got these contracts with good prices, and that was very, very important to us when we take a long-term view on what is an excellent asset.

Thank you. Next question, please.

OK, we're going to come to Graham Parry at Bank of America. Graham, over to you.

Great. Thanks for taking my question. I'm sorry it's more on vaccines. But you said about having US market leadership in the second half on volumes and you said you sort of have a good idea of split. So can you help us understand? I think, you know, up to this point, you've been two thirds of the volume split. For this season, Pfizer started contracting a bit early. You've had Moderna obviously enter the market. So it is two thirds what you'd be aiming for. Or should we just thinking about you having the majority of the market even? Or is it is it less than that? And then secondly, on your peak sales of three billion and return to growth in 2025, does that assume that you are going to have some sort of booster regimen in there? Or can you get there by just rolling out globally? And if you could help us understand on the boosters with the season three vaccine efficacy data for a single dose, they're expecting in the second half. I think your modeling data on the all comers population had suggested that the single administration could drop to around 40 percent in season three, which would. certainly warrant a booster. But in the populations you're now recommended for the over 75s and the comorbid, it looks like those are much higher. They're in the 70s across season one and two. So do you have any sort of predictive modelling data of where vaccine efficacy on those target populations might drop to that would perhaps allow for a booster to be recommended? Thanks.

So, Luke, and then we'll come to Tony on boosting. Sure.

Graham, I won't give you a percentage, but it's market leadership. I think what is not visible to us yet is how much Moderna picked up relative to Pfizer, but we know how much we've picked up. and that's why we're using the term leadership. I think the other thing, of course, one thing is volume, but it has to be multiplied by price, and that's something else that will be more visible in time, so the aggregate revenue. In our forecast, we assume that a booster is required. Tony, I'll hand it over to you for the rest of it.

Yeah, and look, Graham, I'd say at this stage, what I'd, it is really, this is a matter of waiting and seeing. Otherwise, I'm drawing straight lines between two points to get an estimate of where season three is, bearing in mind that the dynamics in season one and season two were very different. And as I mentioned earlier in answering Graham's question, I think it's not just a combination of vaccine efficacy, but also the boost response too. So we'll know more about that when we get ready for ACIP in October.

Thank you. Next question, please.

So we're going to take our next question from Tim Anderson at Wolf Research. So Tim, go ahead, please.

Thank you. A non-vaccine question, which is Zantaxo, an obvious thing for investors downstream of the Delaware ruling. I know Glaxo will say it will continue to defend itself. It'll cite lots of studies in your favor. But in the theoretical event Glaxo were to enter into a broad settlement to try to put all this behind the company? What's realistically the earliest this could happen? Is it safe to assume that would not be possible until 2025, possibly well into 2025? Thank you.

Thanks, Tim. We do absolutely recognise the impact this litigation has had on shareholders. And you're right, I am going to start by reiterating the facts and the science here, which is total scientific consensus that there is absolutely no consistent or reliable evidence that ranitidine increases the risk of any cancer. And so we're going to continue to vigorously defend ourselves against all of the claims and manage the litigation in the best interests of the company and of shareholders. That has been our focus all the way along. And we are confident that we have done so in the process. and that means no change to our growth agenda, no change to our guidance, no change to our investment plans. Our position is based on science and facts, and our focus is to address this in the And as I'm sure you know, there is obviously a limit to what I can say around this litigation, since we need to respect the judicial process and protect the interests of the company. Next question, please.

OK, thanks. Can we go to Mark Purcell at Morgan Stanley? So, Mark, you should be unmuted.

Thank you very much, Nick. Just a few questions. Firstly, on China and vaccines, are you seeing much in the way of emerging domestic competition? I think BCHT has a shingles vaccine, for example. And in that respect, what's the appetite from Ziphy to extend the agreement to Erexfee? The second one on orexivir and boosters. It's been suggested that revaccination only achieves 45% to 65% of peak neutralization titers due to immune interference from the T4 fold-on trimerization T-RAG, which is used by orexivir and brisver as well. So I just wondered if it's the factor and if we've seen this before. And the last one in terms of Nicola, head of the COPD matinee data, late Q3, Q4. I think, Tony, you've described the efficacy is likely to be in the low 20s in terms of reducing exacerbations. Sanofi sees COPD as a 5 billion peak potential across its two assets. So I just wondered if you could help us understand how large the opportunity you see is for your IL-5 focused medicines. Thank you.

We'll come to Luke quickly on China. I mean, I will point out it's quite hard for anyone to come up against Shingrix with an effective vaccine when we've got one with 80% efficacy for 11 years. And then we'll come to Tony on both the booster question and Nucala and the broader opportunities in COPD and COVID. in the pipeline, please, Tony. So Luke first.

Yeah, thanks, Mark. I mean, there is a local competitor to Shingrix. It's a company called Gunway. It's a live attenuated vaccine. So it's Ulster Vax-like. It's licensed. It's 40 plus. But, you know, they get around a quarter of the volume at this point. But again, these are very different patients to the ones that we're targeting. We're targeting... a high out-of-pocket tolerance, willingness to pay population, which is different. In terms of the relationship there, as I said earlier, it's excellent. It's a strategic long-term relationship. And we have had some initial discussions around RSV, and we would very much like to expand the collaboration to include RSV. So just watch this space.

Yeah, thanks, Mark. Just quickly then on the T4 construct, this is obviously something we spotted and we're eager to understand as well. The short answer to that, although we haven't disclosed the data, is there's no evidence of interference. What is a much more likely and common explanation for the boost is the relative waning in the vaccine efficacy in the first instance, and it's generally understood that the greater the waning of efficacy, the greater the boost. So... You'll see more on the T4 folding question when we disclose those data. In terms of... excuse me, COPD and IL-5 and DEPI. Let's just start by putting your comment with regards to Jepilimab versus DEPI into context. Sorry, Carla, into context. I've mentioned this in the past, and I appreciate it. There's a lot of sort of comparative numbers floating around. What's important, as I say, based on the patient population that we've targeted in our Phase 3 study in matinee, which is a broader population and includes patients emphysemic patients. These represent about 30% of the COPD population, so a significant proportion of the approximately 300 million individuals with COPD. That population is more difficult to treat even in the high eosinophilic setting, and because of the different patient mix, and based on what we've seen in the past, That's where my prediction for sort of mid-20s, low to mid-20s percent for matinate comes from. It is not a reflection of relative efficacies of the two molecules. What both classes are showing is that there is a significant response for those with COPD and high EO counts. In this instance in particular, over 300 counts. We're very well placed in the COPD category. arena and evaluation of not just IL-5, but other mechanisms. I would point to, first of all, of course, we're looking forward to the progressing DEPI with once every six months dosing. That is a significant advantage in COPD, even greater than it is in severe asthma. And in addition to that, TSLIP offers a broader opportunity, and the recent data from Amgen and COPD with their TSLIP agent, albeit with a much more frequent dosing regimen, of course, for TESI, suggests that we should also have opportunity there. I'll pause, but there are additional aspects of our COPD portfolio that I look forward to telling you about in the future.

Thank you. Next question, please.

I'll take the next question from Emily Field at Barclays. So, Emily, up to you, please.

Hi, thanks. I'll just ask two quick ones. One on XUSRXV, you know, one of the things that Pfizer talked about yesterday in terms of their XUS contract wins was a desire to simplify the contracting between, you know, having, you know, one option for maternal and older adults. I know this year is mostly going to be U.S. driven for RXV, but, you know, is that something that you see as an obstacle to XUSRXV? And then just, you know, on the HIV guidance, your third year in a row of expecting double digit growth in HIV, you have your CAGR target of six to 8% still intact. Are there any reasons to expect a slowdown in the next couple of years in HIV? Or why not upgrade that guidance? Thank you.

Thank you. Well, let's go to Deborah first on HIV and then we'll come back to get any further comments on.

Yeah, thanks for the question, Emily. So I think in quarter one and actually reiterated on Friday when we did our update post the AIDS conference, we are tracking towards the top of our guidance. As you say, we've had three years of double digit growth. Next year, we have the headwind of the IRA. We've stated very clearly that that's going to be around a 200 million impact. And then, obviously, we've set out very clearly in 2026 what we think the shape and the size of our portfolio is going to be. So we should be reaching 7 billion, if not slightly above, which is what we've kind of shared with you all. in 2026. And then by 2027, obviously, we're moving into a world where we've got 40% of our portfolio in our portfolio value and long acting. So I think at the moment, everything that we've said, 21 to 26 holds firm, we are at the top end of that CAGR. And then as we move into 2027, we remain extremely confident that the long acting medicines in our portfolio will be 40% of our total revenue, if not more, because obviously we're having a very successful period with those medicines at the moment. So no change in our guidance, but just I think you're feeling our increased confidence because of the feedback we get from physicians and patients as to the impact that our long-acting medicines are having and the growing momentum for those medicines.

It's been great to see the progress in the pipeline. Quite a lot of you have been announcing just through into last week too. Luke?

Yeah, thanks, Emily. Short answer is no. I mean, typically the way the contracts and NIPs are constructed is they separate out paediatric population from adult populations and really what counts. And it's different to ACIP, of course, is that the systems are willing to concentrate on single vaccines and separate them out more vigorously versus push them together. And so, you know, our approach is to really... We have an excellent asset here in EREXV. What we want to see is the full profile, as Tony mentioned. We want to see what this product looks like at three years because that is going to have a huge impact on pricing, durability, et cetera, which are all the things, and particularly European contracts, that players concentrate on. So we're happy to let people bid against themselves. We want to sit and wait. um and and see what the true picture of the product is and then build a business based on that and as i said before the numbers are looking very good for orexp um once we have that we will then move ahead and execute thanks luke next question please okay so given that we're coming up to about all the past the hour i'm going to take one more question so apologies to the four of you that didn't uh get to ask question but we're going to go to simon baker at redsburg atlantic so simon over to you please

Thanks very much. And I should respectfully limit myself to one question. It's on a rec suite, but it's one for Tony. In terms of the potential mechanism for lower incidence of dementia, I just wondered what thoughts you had on that. There's been some suggestion that it's an indirect effect. caused by the vaccine suppressing reactivation of HSV-1 virus. But any thoughts you've got on why we're seeing this effect would be much appreciated. Thank you.

Yes, Simon, I presume you meant Shingrix in that rather than Erexi. That's another story. It's fair to say there's very little known here mechanistically. We're investing in further retrospective studies and mechanistic ones. Let me just try and do this quickly. There is a potential that the mechanism may be vascular in nature, It may even be due to, as you say, underlying, let's call it subclinical reactivation. The science is better known, although not by any means comprehensive, for HSV underlying reactivation and therefore inflammation that occurs as a result of that leading to dementia. One can imagine a similar story in the context of shingles, or one could even imagine the constant reactivation impacts microglial function. So there are a range, and I haven't been comprehensive in that answer to avoid spending too much time on it. It's fair to say there's a range of different mechanisms. If you want a comprehensive summary, actually, the Australian paper detailing the epidemiological retrospective outcomes has a really nice summary, and it's completely paragraphed.

Thank you. I mean, it's exciting science to explore still in early stages. In the meantime, this is a very effective vaccine with still a lot of opportunities to penetrate around the world. So with that, Nick, as our last question, a big thank you to everyone. We are really pleased with our Q2 performance and another upgrade to our outlooks and even more looking forward to the ongoing progress in our pipeline and delivering on our short, medium and long-term ambitions. With thanks to everybody for joining us for the call, we'll look forward to following up with you in the coming days.