Good day and welcome everyone, ladies and gentlemen, to the analyst call for GSK fourth quarter 2021 results. I will now hand you over to Nick Stone, Head of Global Investor Relations, who will introduce today's session. Please proceed. Thank you, operator. Hello, everyone. This is Nick, obviously, as the operator's just mentioned. Welcome to our full year and Q4 2021 conference call and webcast for investors and analysts. The presentation was posted to gsk.com, and it was also sent out by email to our distribution list earlier today. Please turn to slide two. This is the usual safe harbor statement, and we'll be making comments at constant exchange rates or CER, unless otherwise stated. Please turn to slide three. This is today's schedule. We'll plan to cover all aspects of our full-year results. The presentation will last around 35 minutes to maximize the opportunity for questions. For those on the phone, please join the queue by pressing star one, and we request in the first instance, if you could ask one question so that everyone has the chance to participate in today's call. Today our speakers are Emma Walmsley, Luke Miels, Deborah Waterhouse, Brian McNamara, Iain Mackay, and Hal Barron. The Q&A portion of the call will be joined by Roger Connor and David Redfern. With that, I will now hand the call over to Emma. Please turn to slide four. Thanks, Nick, and a very warm welcome to everyone. I am delighted to announce our 2021 full-year results. They demonstrate strong financial performance and continued progress against our strategic priorities. For the full year, sales increased 5% and adjusted EPS increased 9%. Excluding the contribution from COVID solutions, we exceeded our raised guidance with adjusted EPS stable for the full year. Sales growth was driven by first-class commercial execution and strong uptake of new products. Pharma delivered 10% growth, new and specialty medicines growing 26%. Double-digit sales in immuno-inflammation, respiratory and oncology, together with sales from Xevudy for COVID-19 all drove this performance. Vaccine sales increased 2%, and consumer healthcare finished the year with 4% growth overall, notably accelerating again in the fourth quarter with sales up 11%. Alongside this, we increased investment for key R&D pipeline programs, expanded support for new and ongoing launches, and maintained a strong focus on cost optimization. This is also reflected in adjusted operating profit growth, which increased 9% for the full year. We see these results as very encouraging and a demonstration of the accelerating momentum we now have at GSK. As we said, 2022 marks a step change in growth for the company and is underscored by the guidance for new GSK, the biopharma business we're giving today of 5%-7% sales growth and 12%-14% adjusted operating profit growth to CER. This includes the anticipated benefit of Biktarvy related royalties, but excludes any contribution from Pandemic Solutions. Ian will provide more detail on this and our overall financial performance in his section. Turning to slide six. 2021 was a year of excellent progress across all three of our long-term strategic priorities. In innovation, we delivered three major product approvals, Jemperli for endometrial cancer, Xevudy for COVID-19, and Apretude, our new long-acting medicine for HIV prevention. We also presented positive phase III data for Daprodustat, a potential best-in-class medicine for treating anemia of chronic kidney disease, and we expect to file this new and exciting medicine with regulators in the first half of 2022. These new medicines are at the forefront of an exciting high-value pipeline we continue to build across prevention and treatment of disease through organic and inorganic delivery. We now have a pipeline of 21 vaccines and 43 medicines, 22 of which are in pivotal studies. This year, we anticipate data readouts on up to seven of the 11 new vaccines and medicines we've identified as key future growth drivers. This includes our RSV vaccine for older adults in the first half of 2022 and several new potential specialty treatments, including those for rheumatoid arthritis, cancer, and hepatitis B. In performance, our decision to prioritize investment in commercial execution to specialty medicines and vaccines is evident in our improving sales growth. Shingrix sales clearly reflected the adverse impact of COVID-19 last year, particularly in the U.S. We exceeded our expectations highlighted at Q3 to deliver sales of GBP 1.7 billion. This year, we do expect to see strong recovery growth and detail on this in a moment. Lastly, on trust, we continue to maintain sector leadership in ESG with our number one ranking in the Dow Jones Sustainability Index and our long-standing leadership in the Access to Medicine Index. Looking ahead, we also aim to deliver ambitious environmental commitments with targets of net zero on carbon and net positive on nature by 2030, and we're also making good progress on diversity and inclusion. ESG will continue to be an integral part of new GSK strategy and investment case. Turning to slide seven. 2022 sees the biggest change in GSK's recent corporate history, with the creation of a new, unique world leader dedicated to consumer healthcare expected in the middle of this year. This will be the culmination of a series of progressive strategic moves successfully executed over the last few years to build significant value and a new consumer healthcare company. We're now in full countdown mode to demerger, and by doing so, our aim is to unlock the potential of both GSK and Consumer Health, to strengthen GSK's balance sheet and to maximize value for all our shareholders. As a new standalone company, the consumer healthcare business is a compelling prospect. It has an outstanding brand portfolio and will be a world leader in consumer health. For prospective investors, it'll offer a highly attractive financial profile of above-category sales growth, sustainable margin expansion, and high, stable cash generation. It will have a fantastic leadership team led by CEO designate Brian McNamara and a board with best-in-class international consumer sector experience, as is already evident with the recent appointment of Sir Dave Lewis as chairman designate. We're gonna provide a lot more detail on this business at our capital markets event later this month, and Brian will give you more on this shortly. For new GSK, as we've previously shared, we've set a new purpose and new ambitions for growth. Our purpose is to unite science, talent, and technology to get ahead of disease together. To deliver scaled human health impact, improved returns to shareholders, and to be a company where outstanding people thrive. This is reflected in the growth commitments and ambition we set out in our investor update in June last year. These represent a significant step change in delivery for GSK, and as I said earlier, start now and are reflected in the guidance we're giving today and the exciting R&D catalysts ahead. Before closing, I would like to say a very big thank you to the more than 94,000 GSK people who helped them to deliver our 2021 performance, and the momentum they have built as we head into this landmark year. Let me now hand over to this team, who will take you through more of the detail. Luke, first of all, over to you. Thanks, Emma. Please turn to slide nine. Let me start with new and specialty, where we made remarkable progress driven by excellent commercial execution. Excluding Xevudy, we delivered 14% sales growth for the year and 10% in Q4, maintaining our double-digit track record. I'm incredibly proud to report that two of our assets exceeded GBP 1 billion in sales for the first time, Trelegy and Nucala. As you've seen, we were able to respond quickly to the strong demand for Xevudy, delivering close to GBP 1 billion in sales of this crucial COVID treatment. Trelegy had a fantastic year despite growing competition, and our unique dual indication in COPD and asthma continues to drive higher demand in the U.S. and Japan. We've also seen very positive trends for our launch in China, where the single inhaler therapy class is growing rapidly and we are winning share in tier one and tier two cities. For Nucala, sales are up 22%, and it remains the leading IL-5 for EOS-driven diseases across key markets. We're pleased to see that our robust approach to lifecycle innovation is driving incremental growth opportunities with the launch of three new indications, EGPA, HS, and nasal polyps in Europe. Benlysta also derived benefit from label expansion with sales up 29% as we reach more new patients with lupus nephritis. Against the backdrop of COVID, we continue to see the importance of having a subcut formulation available for at-home use. As expected, with competitors entering the market, we've seen an overall increase in biologic use, benefiting Benlysta as the leader. In oncology, we continue to make steady progress. BLENREP remains the only off-the-shelf anti-BCMA therapy, and we've expanded our presence to 13 markets. In the U.S., we're driving use in the community setting where most multiple myeloma patients are treated. We're working to reach new physicians as prescribing experience improves perceptions of corneal adverse events management. Closing with Zejula, COVID continues to impact the ovarian cancer market with diagnosis and debulking surgeries still below pre-pandemic levels. Despite the constrained market, Zejula has delivered its strongest quarter of sales to date, and we continue to perform exceptionally well in market share terms with one in two new patients receiving a PARP being prescribed Zejula. A very strong year for new and specialty, and we expect to grow specialty sales by around 10% in 2022, even with Trelegy moving into the new general medicines area. This is before we include the expected contribution from Xevudy. Please turn to slide 10. Moving to vaccines, full-year sales increased by 2%, but decreased by 5% excluding pandemic sales. The overall performance demonstrated the impact on several of our vaccines of COVID. Most impacted was Shingrix, where sales were down 9% of the year, which was slightly better than the outlook we indicated at the nine-month stage. Based on the encouraging early momentum we're seeing, we continue to anticipate a strong sales recovery in 2022. Since Q2 2021, Shingrix has delivered strong sequential growth, reflecting an improvement in trends in the U.S., including solid demand in the non-retail channel, as well as contributions from new European launches and recovery of demand in Germany. We expect this momentum to continue in 2022, despite Omicron's short-term impact. We continue to launch in new markets supported by our unconstrained supply position, and we believe there is a significant pent-up demand in the U.S. Consequently, we continue to expect Shingrix to deliver strong double-digit sales growth in 2022 with record annual sales. This will be a crucial driver of the expected low-teens sales growth in vaccines this year, including pandemic solutions. Looking further ahead, by 2024, we expect Shingrix to be available in 35 markets, representing nearly 90% of the global vaccines market, underscoring our ambition to double Shingrix revenues by 2026. Let me now hand over to Deborah on slide 11. Thank you, Luke. Our goal is to remain innovation leaders in HIV, achieve a mid-single-digit sales CAGR to 2026. Digest the loss of exclusivity of dolutegravir at the end of the decade through the changing mix of our portfolio and the success of our pipeline. Our Q4 and full-year results demonstrate positive momentum towards delivering on these objectives. Sales grew 3% both for Q4 and for the year. Within this, we achieved a noticeable acceleration in our innovation sales, which now stand at 34% of our portfolio and all regions reported growth. This acceleration in growth results from strong commercial execution behind our two drug regimens and Dovato in particular. Sales of Dovato more than doubled to GBP 787 million and are fast approaching 20% of the total HIV sales. Dolutegravir-based regimens now hold the number one position in the share of the switched market across the U.S. and Europe. Based on this strong momentum, we believe Dovato is on track to deliver GBP 1 billion of sales in 2022, with further significant growth potential beyond. Please turn to slide 12. Turning to our injectable portfolio, Cabenuva is our first-in-class long-acting regimen for the treatment of HIV, for which we received FDA approval last week for every two-month dosing. As with any new class of medicine, sales of Cabenuva will take time to build, and the COVID environment is constraining switch activity, particularly where a patient needs to visit a physician's office. Nevertheless, over 4,500 people living with HIV are already taking Cabenuva/Vocabria/Rekambys, and the outlook for this important new medicine is strong brand recognition and market access exceeding 80%. Moving on to prevention, we ended 2021 on a high with the FDA approval of Apretude, the world's first long-acting injectable for the prevention of HIV, dosed every two months. HIV prevention is a huge unmet need as current medical options are associated with stigma and adherence issues. Apretude not only addresses these concerns, but it has demonstrated superior efficacy over daily oral tablets. As a new paradigm, we need to educate physicians, patients, and payers, so this year our focus is on building awareness and access for Apretude. The early signs are encouraging with positive feedback from patients and prescribers and with political will supportive of methods of HIV prevention. Consequently, we remain confident that Apretude will deliver significant benefits to patients in the years ahead, as well as significant commercial value beginning in 2023. With that, I will hand over to Brian, and we will move on to slide 13. Thanks, Deborah. Now turning to consumer healthcare. Sales for the full year, excluding brands divested under review, increased by 4% at constant exchange rates, despite a negative 1% impact of COVID on cold and flu sales, building on the 4% growth we delivered in 2020. International grew 9%, with emerging markets performing particularly well, including East Africa growing double digits. U.S. sales increased 2%, and Europe was broadly stable, with both regions building momentum through the year. Q4 growth was strong, up 11% at constant exchange rates, albeit against a weaker comparator of 1% growth in 2020, with all categories performing well. Cold and flu sales rebounded in Q4, with European sales above 2019, and U.S. sales only slightly below. From a category perspective for the full year, oral health sales increased 5%, with broad-based growth in key markets reflecting brand strength, strong execution, and successful innovation. Pain relief grew high single digits. This was primarily driven by Panadol, which benefited from seasonal demand in the second half of the year. Voltaren delivered mid-single-digit growth despite the expected introduction of U.S. private label earlier in the year. Vitamins, minerals, and supplements grew 4%, continuing the momentum on a very strong year-over-year comparator. Centrum growth in the second half was particularly strong due to increased capacity and retailer stocking. Respiratory declined 1%, with strong growth in allergy offset by a mid-single-digit decline of our cold and flu products. Q4 rebounded, delivering 40% growth due to a return of a more typical cold and flu demand. Although it fell just short of offsetting the unprecedented market declines in Q1. Digestive health and other sales were up mid-single digits, with broad-based growth across skin, digestive health, and smokers' health. On e-commerce, year-to-date sales grew in the high 20% range and is now 8% of sales, with good growth in key regions such as China. Our ongoing investment in digital capabilities continue to position us well for growth in this vital channel. We've also delivered strong margin progression for the year of 200 basis points at constant exchange rates, while at the same time increasing investment in our brands. Operational efficiencies on top of synergies, along with pricing, have more than offset the impact of divestments and inflation in the year. Overall, looking at sales growth over the last two years, we've delivered a CAGR of over 4% despite net COVID headwinds. We're able to successfully capitalize on tailwinds created by increased vitamin mineral supplement demand. However, these were more than offset by the decline in respiratory as a result of the historically low cold and flu season. This clearly demonstrates the strength and breadth of our portfolio and the capabilities we built through the two most significant transactions in the industry, coupled with extensive portfolio rationalization. This positions us to deliver sustained market outperformance with a 4%-6% medium-term annual sales outlook. Please turn to slide 14. With regards to the upcoming separation, I'm delighted that Dave Lewis was recently appointed as chair designate, and my executive leadership team has now been announced. I hope you will join us at our Capital Markets Day, which will take place virtually on February twenty-eighth. We will lay out our strategic priorities, key growth drivers, and detailed financial information. The team and I will share both a global and regional overview, including our innovation, digital and operational capabilities, as well as our capital allocation priorities as a newly listed company. Most importantly, we will set out how we will deliver the growth, category outperformance, and attractive sustainable returns that we are confident this business can achieve in the medium term. With that, I'll hand it over to Iain. Please turn to slide 15. Thanks, Brian. As I cover the financials, references to growth are at constant exchange rates unless stated today. On slide 16, there's a summary of the group's results for the full year 2021, and I'll focus my comments on the full-year performance. Turnover was GBP 34.1 billion, up 5%, and adjusted operating profit was GBP 8.8 billion, up 9%. Total earnings per share were 87.6 pence, down 13%, while adjusted earnings per share was 113.2 pence, up 9%. Pandemic solutions contributed approximately nine points of growth in adjusted earnings per share. On currency, there was a headwind of 5% in sales and 11% in adjusted earnings per share, in particular due to the strengthening of sterling against the US dollar relative to 2020. Turning to the next slide. This slide summarizes the reconciliation of our total to adjusted results. The main adjusting items of note for the year were in disposals and other, which primarily reflected profits across several divestments, including the gain on disposal of rights to royalty stream for cabozantinib in Q1, the gain on disposal of the Cephalexin business in Q4, and a significant positive revaluation of deferred tax assets in the U.K. resulting from the Q2 enactment of the 2021 U.K. Finance Bill. Finally, in transaction related, the main factor was the movement on the ViiV CVL, which included the impact of the settlement with Gilead. My comments from here onwards are on adjusted results unless stated otherwise. Turning to slide 18. Key drivers of revenues and profits for the group in 2021 compared to 2020 are set out here. Revenues grew 5% overall. Revenues from our COVID solutions contributed around four percentage points of that growth. Positive operating leverage from higher sales in the year was supported by continued focus on cost control and the benefits and synergies resulting from restructuring across the group with SG&A down 1%. This included favorable legal settlements compared to increased legal costs in 2020, which primarily impacted Q1 and one-off benefits in pensions and insurance in Q4. Alongside these benefits, we continued to prioritize investing in our pipeline and R&D expenditures increased by 8%. This resulted in an adjusted operating profit increase of 9%, with pandemic solutions contributing seven percentage points of that growth. The full year margin was 25.8% and 90 basis points higher than 2020 at constant exchange rates. Turning to slide 19. Moving to the bottom half of the P&L, I'd highlight that the effective tax rate of 17.5% was aligned with expectations and that interest expense of GBP 753 million was slightly lower than expected, primarily due to favorable foreign exchange. Next, I'll briefly cover free cash flow for the year before going into more detail on the financials of each business. On slide 20, in 2021, we generated GBP 4.4 billion of free cash flow. This was a step down versus 2020 and consistent with our outlook given in February last year. The positive factors of increased adjusted operating profit at CER and lower dividends to non-controlling interests were more than offset by increased purchases of intangible assets, including our collaborations with Alector and Arctus from Q3, reduced proceeds following completion of the Consumer Brands disposal program, adverse timing of returns and rebates compared to 2020, and adverse exchange impacts. Net cash generated from operations for the group was GBP 8 billion. We expect to share comparators for new GSK cash flow later in the first half. In 2022, we expect cash generated from operations for new GSK on a like-for-like basis to be higher than 2021 as a result of the Gilead settlement and increased adjusted operating profit. This will be partly offset by lower cash generated from lower margin COVID solutions and FX headwinds related to the phasing of payments in 2021 and continued generics impact on the U.S. respiratory portfolio. Turning to performance of the pharma business on slide 21. Overall, pharmaceutical revenues grew 10%, driven by strong growth in new and specialty medicines, favorable U.S. return on rebate adjustments, and sales of Xevudy, which contributed six percentage points of growth. But within this 10% growth, established pharma sales decreased 6% in 2021, which was slightly better than expected. The pharma operating margin was 26.4% for 2021. The increase in profit margin primarily reflected the positive operating leverage from the increased sales, including the favorable pricing in AER, continued tight cost control and restructuring benefits. This was partly offset by continued investment in R&D and HIV product launches. Turning to slide 22. Overall, vaccine sales grew 10%. Excluding pandemic adjuvant revenue, sales decreased 5%, primarily driven by Shingrix dynamics, which Luke described. We continue to be very confident in the demand for our vaccines. Notably, during 2022, we expect Shingrix to deliver record sales with strong double-digit growth. The operating margin was 33.3%. The decrease in operating profit and margin primarily reflected higher supply chain costs resulting from lower demand. This was accompanied by an increased R&D investment of 34% as we progressed our RSV and meningitis development programs and invested in our mRNA platform. Higher royalty income and beneficial mix from pandemic adjuvant sales partly offset these factors. Q4 sales were down 7%, reflecting the tough comparison in 2020 and strong Shingrix sales. Turning to slide 23, revenues in consumer healthcare increased 4%, excluding brands either divested or under review. Including those brands, turnover was flat. Brian outlined among the main drivers earlier. The operating margin was 23.3%, up 200 basis points at CER versus last year due to sales growth, including favorable pricing and mix, and strong synergy delivery. This was partially offset by a 120 basis point impact from divested brands in addition to commodity and freight cost pressures. The strong 11% sales growth, excluding brands divested or under review in Q4, is an encouraging sign of momentum as the business moves into 2022. Turning to slide 24. I'll close with our guidance for new GSK in 2022, all of which excludes the commercial impact of our Covid solutions. Our guidance is predicated on the consumer healthcare business being de-merged in mid-2022. We expect the formal criteria for treating consumer healthcare as a discontinued operation to be satisfied in Q2. GSK will continue to consolidate the business for reporting purposes until the planned de-merger. As Brian mentioned earlier, the consumer healthcare capital markets day will set out the strategic priorities, key growth drivers, and detailed financial information that underpin our confidence in the compelling medium-term outlooks for that company. For New GSK, 2022 will see a step change in growth. We expect New GSK sales growth to be between 5%-7% in 2022. Investment in the business for growth will continue in a focused and controlled fashion, and so we expect SG&A and R&D to increase their rates similar to sales. We expect cost of goods sold to increase at a slower rate than sales. As a result, our guidance for adjusted operating profit is for between 12% and 14% growth. This includes the anticipated benefit of the ViiV-related royalties contributing around two percentage points of adjusted operating profit growth. On the outlook for COVID solutions in 2022, based on known binding agreements with governments, we expect that COVID solutions will contribute a similar sales level to 2021, but a substantially reduced profit contribution due to the increased proportion of lower margins of Xevudy sales. We expect this to reduce new GSK adjusted operating profit growth, including COVID solutions in both years, by between 5% and 7%. We'll provide quarterly updates as future contracting and binding agreements progress. With regards to dividend policy in 2022, the total expected cash distribution and the respective dividend payout ratios for each company are unchanged from what we communicated at our investor update last June. GSK expects to pay GBP 0.49 per share, comprising GBP 0.44 per share for new GSK and GBP 0.05 per share representing consumer healthcare while still part of the group. Consumer healthcare's dividend in the second half of 2022 is subject to review and approval by the consumer healthcare board. This is expected to be around GBP 0.03 per share and has been adjusted to reflect the total number of consumer shares that are expected to be in issue upon demerger, and more details provided in the appendix. Given the complexities associated with demerging a significant operating segment of the company, we'll provide adjusted earnings per share guidance at our Q2 results following the demerger. To help with modeling new GSK, a reconciliation of the 2021 results to reflect new reporting format is expected to become available later in the first half. As a reminder, we'll be presenting a single new GSK operating margin in the future. In summary, we believe the business momentum built from the excellent work of our teams in 2021 sets us up for a step change in growth for new GSK in 2022. With that, I'll hand over to Hal. Thanks, Ian. I'll provide a short update on our progress in R&D over the past year and highlight some of the key upcoming pipeline milestones. Please turn to slide 26. As we set out last June, the transformation of our R&D in 2018 has resulted in a significantly stronger pipeline and improved productivity across multiple metrics. In 2021, we continued to build on this momentum. In terms of late-stage pipeline achievements, advancements, we achieved the first regulatory approval for three new medicines in 2021, Apretude, Xevudy, and Jemperli, as well as seven regulatory submissions. As Luke mentioned earlier, our approach to lifecycle innovation is also delivering with five additional approvals in 2021 for Nucala and Benlysta. We also reported positive pivotal data on three assets, including Daprodustat, which I'll cover in more detail in a moment, and started eight new phase III trials. In total, we have delivered 13 major regulatory approvals from 2017, which is top quartile performance for the industry, and four of these assets have already achieved so-called blockbuster status. As a reminder, we expect the medicines and vaccines approved between 2017 and 2021 to contribute around 60% of new GSK's 2021-2026 sales growth, with the anticipated pipeline approvals contributing another 40%. We're also bringing forward the next generation of innovative assets into our pipeline, driven by our focus on the science of the immune system, human genetics, and advanced technologies. In 2021, we moved 19 assets into phase I or phase II trials, which are the direct result of our focus on human genetics and functional genomics with our overarching vision to use the human as the model organism. An excellent example of this is our anti-IL-18 neutralizing antibody, so-called GSK 806, which is being developed to treat patients with atopic dermatitis, where there is strong genetic rationale for this target. The second example is GSK 130, a monoclonal antibody that just entered phase I and targets IL-7, which is genetically associated with developing multiple sclerosis. In oncology, our internal work on functional genomics has identified more than 10 target candidates in research for evaluation in the field of synthetic lethality. Our collaboration with IDEAYA has three synthetic lethal targets. The most advanced is our MAT2A inhibitor, which is in phase I for patients with tumor where MTAP is deleted, which is common in solid tumors. Overall, I'm very excited about the potential of this next wave of medicines and vaccines in our pipeline. Please turn to slide 27. This slide highlights two major pipeline achievements delivered towards the end of 2021. I've previously spoken before about Daprodustat, our HIF prolyl hydroxylase inhibitor, a target we chose to pursue because, again, genetics strongly suggested a role in stimulating erythropoiesis. The ASCEND phase III program recruited over 8,000 patients in well-designed studies using active controls and delivered very consistent efficacy and safety results in both dialysis and non-dialysis patients. The results uniquely demonstrated that Daprodustat met the primary endpoint of non-inferiority to an erythropoietin-stimulating agent in terms of cardiovascular safety and was shown to be as effective as standard of care in treating to a target hemoglobin range. We believe these data position Daprodustat as a best-in-class oral agent for treating patients with anemia of chronic kidney disease and are on track to submit these data in the first half of this year. The second key pipeline achievement was the approval of Apretude for the prevention of HIV based on extremely impressive efficacy results. This exciting milestone was well covered by Deborah earlier, so let's turn to slide 28. Looking to the year ahead, this slide focuses on the important pipeline milestones we anticipate in the first half of 2022. RSV disease represents a significant unmet medical need, with RSV infections accounting for around 180,000 hospitalizations each year and about 14,000 deaths in the over 65 population in the U.S. alone. The unique design of our antigen/adjuvant combination induces a strong neutralizing antibody titers and T cell responses against both RSV A and B in the phase II trials, which is critical to protect an older adult population who are at increased risk for RSV disease. From the literature and our trial data, we know that older adults typically have a lower T cell response when compared to younger populations, and our RSV older adult vaccine utilizes our AS01 adjuvant to overcome this deficiency. Our RSV older adult trial is expected to read out ahead of our original timelines, with headline data expected during the first half of 2022, and filing is anticipated before year-end, potentially putting us on a path for inclusion in the June 2023 ACIP meeting. Please turn to slide 29. The next two years will see R&D continue to deliver important news flow on several potential new medicines and vaccines within our late-stage pipeline. In 2022, we anticipate late-stage milestones from up to seven of the 11 new medicines we highlighted at the investor update in June last year, including those I've already mentioned. I'll take two minutes to highlight some of the other readouts that I'm most excited about. I'll start with otilimab, where we have three phase III trials reading out in 2022, contRAst-1, contRAst-2, and contRAst-3. These data will define the efficacy and safety of our anti-GM-CSF antibody, which has the potential to deliver an entirely new mechanism of action for patients with rheumatoid arthritis. Data from the phase IIb trials suggested a unique reduction in pain, which we believe could be driven by CCL17, the most overexpressed protein by monocytes when stimulated by GM-CSF. Based on this finding, we moved GSK3858279, a CCL17 monoclonal antibody, into development to treat patients with RA arthritic pain, and we expect initial data to be available later this year. In addition, we expect data on BLENREP with pivotal DREAMM-3 trial readout in patients with third-line multiple myeloma. This is an important study as it'll give us the first progression-free survival and overall survival data on BLENREP in a randomized setting. We also anticipate presenting data around the middle of this year on BLENREP in combination with a gamma-secretase inhibitor. These data will also help inform our strategy for treating patients in the frontline setting. I also want to briefly mention, bepirovirsen, our HBV ASO, which we plan to present data on in the middle of the year from our phase IIb trial investigating the treatment of patients with chronic hepatitis B. There's a significant unmet medical need for these patients with over around 300 million patients living with hepatitis B, and the disease is responsible for over 900,000 deaths each year. In addition to these late-stage, we plan at least three major regulatory submissions in 2022, including daprodustat, RSV for older adults, and BLENREP in the third-line setting. Lastly, we have recently announced several impressive leadership appointments, including Phil Dormitzer as the head of vaccines R&D, who joined us from Pfizer, and Hesham Abdullah, who was promoted to the head of Clinical Oncology. In January, we also announced that Tony Wood would be our new Chief Scientific Officer from the first of August, and I'm delighted about his appointment. Tony is a person and scientist of the highest quality who is integral to building our new approach to R&D, and his appointment and expertise deepen our commitment to this strategy, and I'm positive that Tony will be an outstanding leader for GSK R&D. I'm also pleased to remain part of GSK beyond August as I transition to a non-executive board member and support Tony and the team to deliver on the promise of our exciting pipeline. In summary, 2022 will be an exciting year for our high-quality pipeline, and I remain very confident that we'll continue to advance the standard of care for patients and deliver value to shareholders. With that, I'll hand it back to Emma. Thank you. Let's move to Q&A, please. Operator? Thank you. The first question is coming from the line of James Gordon from JPM. Please go ahead. Hello, James Gordon, JP Morgan. Thanks for taking the questions. I just have one question. I'll ask a question about Specialty Pharma. I saw Specialty Pharma sales were a little bit light versus consensus expectations today. I know growth is gonna be approximately 10% in 2022, which sounds a little bit more cautious than the double-digit medium-term outlook that you issued in June last year. Have things got any toughness to these assets? Is it gonna be a bit of a back-end weighted CAGR for Specialty Pharma? And what could drive an inflection, particularly in oncology? Do we need more data, or is it really about just COVID diagnoses, or COVID going getting better and then more diagnoses for these conditions? If I could. Not another question, just a clarification. If I look at the guidance, the 5%-7% core EBIT headwind for COVID-19 product contribution, it looks like it's effectively assuming that you sell the 1 million doses for Xevudy that you've already got an order for, but there's no more sales at all for the rest of the year. Just a clarification, is that right? The assumption is that beyond the orders you've already got, you won't sell any more Xevudy this year. Well, I'm gonna ask Iain. Thanks, James, for that one question and then clarification. I'll ask Iain to pick up exactly first on the forecast forward for COVID solutions. Just remembering it's not in any of our guidance either for this year or for the year ahead. Obviously, there's still some uncertainty about how that market will play out. We'll come to Iain first. Then just more broadly on the total outlook. Obviously, we've guided more than 5% top line on a five-year outlook and, as you said, double-digit for specialty and high single-digit for vaccines. We're very clear that that isn't, at an overall level, something that we're expecting anyone to wait for, which is why we're starting strong and starting now in 2022 with 5%-7%. Clearly, the mix of that is dependent on some of the pipeline, both, coming and recent launches maturing into more scaled contributions in specialty. I'm gonna ask Luke to comment a bit more on, some of the shape of that, and then perhaps, Hal, we can come back to you to talk about some of the pipeline, catalysts further out in specialty medicines more broadly. First of all, Ian, on, Yeah. No, easy answer, James. Pretty much exactly what we wrote in our earnings release, which we expect pandemic sales were around GBP 1.4 billion from Xevudy. That reflects binding agreements that we have in place at this point in time. To the extent there are any further binding agreements that would inform any updates, we'll provide those on a quarterly basis. Okay? Luke, in terms of momentum and outlook on Specialty. Yeah. Thanks, James. Look, I think the momentum, for example, oncology is very strong. We're getting five scripts for every one that Breztri gets. Zejula is very healthy. I think the primary challenge is, and we've placed this in the backup in the appendix, is just the continued slow recovery of ovarian cancer diagnosis, which is still down by 22%. Debulking surgeries are down by 17%. That's taking longer to resolve than we expected, which is obviously very sad. We expect that when those women present, their disease is gonna be more advanced. That is having an impact. There was also some pricing pressure emerging in the IL-5 class in Q4. Thank you. Perhaps Deborah, but just before we go to Hal. Obviously, one of the areas that's going to continue to build in contribution is the innovation in HIV. Deborah, to you first. Yeah. I think at the business investor update at the end of November, we committed to mid-single digit CAGR between now and 2026, and that's an acceleration of growth from where we've been over the last few years, where if you remember, we've had kind of over the last three, 1%, 1%, and then obviously in 2021, we're at 3%. You can see that progressive growth acceleration. We feel very positive about our ability to deliver that mid-single digit CAGR on the back of the tremendous, you know, progress that we've made with Dovato, but also the fact that you'll get more material contribution from Cabenuva, certainly 2022 and beyond. Apretude 2023 and beyond. I'm feeling really, you know, excited and confident about the future in the HIV part of Specialty. Thank you. Hal, anything to add on catalysts to follow? Yeah. You know, there's been a lot of catalysts in the last 12 months, as I've pointed out with the three regulatory approvals and the seven major filings, three pivotal data readouts in the eight phase III starts. I think it's also important now that we have 64 medicines and vaccines in the pipeline, 22 of which are in late-stage pivotal studies. So you're gonna be seeing a lot of readouts. Most importantly, in 2022, we've talked about the 11 key assets and in 2022, we're hoping that up to seven of those will actually have readouts, including RSV OA in the first half. Otilimab, as I mentioned, the second half, BLENREP, DREAMM-3 in the second half. RSV Maternal, which we should get data on the second half. The meningococcal pentavalent ABCWY in the second half. Gemcitabine will have a readout both in the conversion of the GARNET study as well as data in RUBY. As I mentioned a little earlier, phase IIb, bepirovirsen for the B-Clear study in HBV. That, of course, complements the wonderful data that we received earlier with Apretude and the recent approval. Really quite a lot of catalyst. I think fundamentally, James, it's just worth reminding ourselves that in new and specialty, our growth last year was 26%, and even excluding the contribution from Zejula, it's 14%. There's a lot of reasons for confidence in strong executional performance of growth and then, of course, all the pipeline to add to that. Next question, please. The next question is coming from the line of Keyur Parekh from Goldman Sachs. Please go ahead. Hi, thank you. Hopefully, you can hear me okay. Two questions, please. The first one for Deborah, just following up on your comments about the HIV, and I see that you're guiding to about GBP 2 billion in kind of revenue contribution from the long-acting regimens by 2026. But what I would be interested in, Deborah, is your perspectives on how do you see that long-acting market developing beyond 2026 into the kind of the 2030s, given the news flow we've had from islatravir and kind of just the early feedback you've had on the prep launch. So just kinda how are you framing that longer-term outlook for that business? And then secondly, Hal, many congratulations on all your successes and kind of best of luck in your new role. As you sit here today and look at the progress kind of Glaxo have made from an R&D perspective over the last few years, how much of what you set out to do at the start have you achieved so far? How much more do you think kind of Glaxo as a company needs to achieve? What role do you think you might be playing in that from a non-executive perspective? Thank you. Thanks very much, Keyur. Well, directly to Deborah and then Hal, please. Yeah. Thanks for the question. I mean, we see the long-acting market from a treatment perspective to be about GBP 4-5 million in value by the end of the 2030s. Actually, by the end of the 2020s, we see GBP 4-5 billion in value for the prep market. Both the same kind of value from a long-acting value for the 2020s decade. I think, despite the fact that we've seen Islatravir have some challenges, we've seen that Gilead are also extremely committed to long-acting themselves with lenacapavir, and they outlined in their results, obviously, all the partners that they're looking at for lenacapavir. I think what you're hearing from both of the big players in the market is that there is a big opportunity to serve the needs of patients by delivering innovative new medicines into both the prevention and the treatment part of the market. The other thing that I find encouraging, so obviously, you know, Merck will continue to look at Islatravir, but the piece that I find encouraging is the real energy around the evolution of the prep market in the United States. If you remember, Ending the Epidemic is a commitment that there will be, you know, significantly less new infections as the decade progresses to the point at which there is a 90% reduction by 2030. The government in the U.S. is extremely energized at the moment around how they're gonna deliver against that target. There's a lot of dialogue occurring, and there's a lot of encouraging sounds about how we could see that prep market evolve, given that only 23% of those that could benefit from prep are actually getting a medicine today. I think our the numbers that we talked about at the BIU in June and again in November are still what we're expecting in terms of long-acting treatment markets, long-acting prep markets, both each being around £4 billion-£5 billion by the end of the 2020s. The other thing is, I mean, maybe worth mentioning is the very exciting next-gen pipeline that's coming through in longer acting that you and Kim covered off in November when we get into longer acting even beyond the near term. Products we're launching. Yeah, we're really excited about that. We have, if you remember, three areas where we're really focusing: an at-home treatment, an ultra-long-acting treatment, which will be clinic delivered, and then obviously we're focusing on cure. Where we are today with, you know, with Apretude and Cabenuva, we're absolutely not stopping there. That's why we're so confident about our ability to move past the dolutegravir loss of exclusivity and still, you know, replace a lot of that revenue that is lost and have a very vibrant HIV business at the end of the decade and beyond. You know, obviously, we've got integrases at the core, both with cabotegravir and then the next generations that we've you know agreed to in-license from Shionogi. We've got the partner options that we're looking at, and we should be able to pick a partner for cabotegravir. For at-home and long-acting, in 2024 as data reads out and informs our choices. Really excited about the pathway, which is very clear before us and the choice points and when data will be available are also very clear, and we'll keep you all updated. Thank you. Hal. Thanks for the comment and question, Keyur. First let me say I'm actually very proud of what we've in the R&D organization have accomplished over the past four years. There's so many different metrics one could use to highlight that today. The pipeline has 64 medicines and vaccines, 22 of which are in pivotal studies. We have 13 novel assets in phase III. As Emma Walmsley mentioned earlier, we've doubled the number of phase III assets over the last couple of years. Probably the most important metric that I look at is how much of the R&D success and the pipeline are driving the CAGRs that we are proposing, which are top quartile relative to our peers. When you look back, there's been 13 new medicines and vaccines approved over the last 4.25 years or so, and that's driving about 60% of the really terrific performance that we've committed to. Importantly, on a risk-adjusted basis, the late-stage pipeline, and this again excludes all of phase I and phase II, is expected on an adjusted basis to drive another 40% of that growth. I think those are really important metrics. There's quite a lot of other metrics, but I think we've made quite a bit of progress. You asked what's not finished. Well, I think if you think about being the head of R&D at any pharma company or biotech company, you know, you never leave the job finished. The job. There's always more assets you can progress. There's more programs, there's more lifecycle innovation. As long as the success rate is where it is, there's still an enormous opportunity to transform how targets are discovered. I'm very excited about how much progress we've made on using the human as the model organism, using human genetics, functional genomics, and machine learning to evolve our strategy. In fact, if you think about what's coming, we have around 40 collaboration projects with 23andMe on genetically validated targets. We have 10 synthetic lethal programs that were internally developed. We have three with IDEAYA Biosciences. We have programs with the Broad Institute, we have programs with Adrestia, a number of collaboration programs, the anti-sortilin program. A number of genetically validated targets that over the next five to 10 years are gonna evolve. I'm looking forward to my transition from being the CSO to the board member to help Tony Wood, who is an outstanding leader, an outstanding scientist, an outstanding person, and I'm hoping that I can play some role in helping him evolve our strategy to be able to accomplish all these things that we're hoping to do. I would just reiterate that what you know matters most in these transitions is extremely well-planned and strategic and thoughtful succession. We are all very confident we're gonna accelerate the momentum of the execution of this strategy that objectively and quantitatively can really be seen to be bearing results already. We're absolutely thrilled that Hal is still gonna be part of that adventure as a board member, as a science committee member, and with some additional commitments that I know he's more than happily made to support the R&D organization, its advisory boards, some connectivity in his part of the world. You know, we are obviously very proud of him for his next steps too and excited for the path ahead. Next question, please. Hello? The next question is coming from the line of Graham Parry from Bank of America. Please go ahead. Great. Thanks for taking my question. So firstly, on the RSV vaccine, looks like Pfizer's on track to publish RSV older adults vaccine data Q1 or Q2, possibly ahead of GSK. Are you seeing that the hurdle rate for both their vaccine and yours is the same level of protection you saw in J&J's CYPRESS phase II trial? And how confident are you that your vaccine can match those levels? Do you see that by not waiting for a full RSV season that Pfizer could gain any sort of time advantage to the market to you? Or is it just a seasonal issue? And then secondly, on COGS, that was negatively impacted by both Xevudy and write-downs in the quarter. Just wonder if you could quantify how much, for each in basis points and just what the right sort of longer-term COGS ratio ex pandemic we should be thinking about? Right. Briefly, Iain, could you comment on COGS and then Hal on RSV? Well, Graham, again, we provide a little bit of a steer in terms of the impact of Xevudy in terms of operating margin. We participate in about 27.3% of the economics from sales in Xevudy. When you sort of translate that through to the overall profitability, we provide some steer in our earnings release in terms of what that means. There is within the team a very strong focus on continuing to drive productivity and efficiency across the supply chain through COGS. As we talked about in the investor update in June, that focus remains consistent and is part of what informs our progress in operating profit growth in 2022 and beyond. Hal? Yeah. Thanks, Graham. You know, our RSV program is actually ahead of schedule, as I mentioned. Enrollment is completed, and we expect the data for the trial to read out this half, H1 2022. In terms of, it's important to keep in mind that we have a pretty unique vaccine because, as you know, we have the protein with the AS01 adjuvant. We think this is very important component because as I mentioned earlier, the elderly who are obviously at risk for the complications of this infection over time lose their both adaptive and innate sense of being able to combat this infection. Particularly you see a abnormality in their T cell response. We're you know optimistic that the combination of the right protein in the RSVPreF3 OA, which neutralizes both the RSV and A and B forms of the virus, as well as having the T cell modulatory component with the adjuvant, will give us the highest chance of success in this for this vaccine. Thanks. Next question, please. This question is coming from the line of Simon Baker, Redburn. Please go ahead. Thank you for taking my question. Just going back to Graham's question on COGS. Ian, you pointed out the impact of Xevudy, but also in the press release, you discussed other headwinds on the gross margin in 2021. Presumably, in light of the comment you made on R&D, SG&A, and the guidance for operating profit, they will fall away in their entirety in 2022. I just wonder if you could give us any other non-Xevudy tailwinds and headwinds we should be thinking about for COGS in 2022. Thanks so much. Well, what I was referring to in 2021 was specifically some higher inventory costs within COGS and lower demand, particularly within the vaccines business. That was one key driver. Another factor which was possibly more noticeable within our consumer business, but as well as it was managed there, equally managed within the biopharma business, was around input costs. Freight as an example, where I think the team was incredibly successful in driving productivity to offset some of that inflationary pressures. That focus, and we believe capability, continues through 2022. There are a couple of factors that were unique to 2021 that I've mentioned that we do not see at this point in time recurring in 2022. just that overall focus in driving efficiency, productivity through the commercial cycle across our businesses in managing cost of goods sold overall, where we've built a good track record over the last couple of years, we expect to be able to sustain over the coming years. It's just good old-fashioned productivity through the supply chain, the procurement channels, good linkage with commercial cycle in terms of understanding demand in market and managing inventory accordingly. Thank you. Next question, please. Next question. Could you please just limit your questions to one question due to the time remaining? Thank you. The next one is coming from Tim Anderson, Wolfe Research. Oh, thank you. I have a question, just a pipeline question. Otilimab, you call out the phase III readout in RA in the second half, as an important 2022 catalyst. To me, that phase II data always looked a little questionable. I know Glaxo's the only company chasing this mechanism. Sometimes that's a red flag because most of the time other companies crowd into new and exciting areas. My question is your confidence in that readout and in this being a commercially meaningful asset. I'm trying to figure out how much this sort of thing is in your kind of longer term forecast and how much risk adjusting you do on this particular asset. Thank you. Hal? You know, Tim, thanks for the question. Otilimab's a pretty interesting pathway. It's very novel. Typically when you have such a novel pathway, you don't see the so-called crowding until, of course, the data reads out positively, which then results in crowding. I'm pretty optimistic this trial will hit, to be honest. You have to remember that there's a design where it's against placebo for the first 12 weeks and then active comparator against IL-6 in one study and the JAK class in the other. The signal for efficacy, I think, was pretty clear. But your point is well taken that not every endpoint in the phase IIb was positive, but quite a few were. I think the area that is a little more speculative, but again, I'm cautiously optimistic, is where we saw signals to a more significant reduction in the clinical pain scores than one would expect for the reduction in things like sed rate and CRP levels that are biochemistry measures of the disease severity. We looked at that data carefully and overlaid it with the preclinical data where we had mouse data with the CCL17 knockout, which as I mentioned earlier, is the most overexpressed protein when GM-CSF is applied to monocytes. In that CCL17 knockout mouse study in an osteoarthritic neuropathic pain model, there was a dramatic reduction in pain with the knockout. That gave us more credibility that that signal, if you will, in phase IIb might be real. Again, we're gonna have readout from the CCL17 mAb data this. Actually, probably in Q2, maybe Q3. I think that will give us further confidence in the program. Again, just to highlight, I'm reasonably optimistic that this will actually benefit patients. It'll be a novel class, and hopefully, we'll see some important reductions in pain. Maybe I can just turn it over to Luke to comment on his interest in the commercial component and how he sees this fitting in the landscape of RA patients. Sure. Thanks, Hal. I mean, thanks, Tim, for the question. I mean, the numbers of patients here are enormous, right? I mean, there's about 1 million in the U.S. on biologics, on JAKs. Many of them are cycling, as we know. What's interesting, if you look at the new data with JAKs, we have market research that indicates about 65% of doctors want to reduce their usage of JAKs, and that there could be an opportunity for alternative non-JAK, non-TNF mechanisms for about 40%. There's clearly a demand for patients. I think the genericization and biosimilar is also gonna move patients to Onto targeted therapies earlier and therefore will cycle earlier. I think for the other programs, there's been GM-CSF in the past, and a number of them have had some issues in preclinical on non-human primate models, et cetera. Again, hopefully we can thread the needle here. As Hal said, contRAst-3, I think, is really interesting against the IL-6, which is naturally a primary competitor. Then, of course, we've got contRAst-1 and contRAst-2 against tofacitinib and methotrexate by itself. I think an interesting program. Thanks. Next question, please. Next question is coming from the line of Emmanuel Papadakis from DB. Please go ahead. Thank you for taking the question. Maybe I'll take a question on vaccines, please. Flu market outlook has been pretty topical of late. We've heard market leaders talk at length about reasons to believe in the resilient outlook for egg-based quadrivalent vaccines. I would love to hear your perspective on the room for mRNA-based vaccines to improve upon both the production aspects and risk benefits of current egg-based vaccines over the coming years, given you have some involvement on both sides of that equation. Perhaps you could also take the opportunity to give us a quick update on CureVac partnership on both the second-gen COVID and flu programs. Thank you. Sure. Well, why don't we hear from Roger just on the more strategic outlook for flu? 'Cause I know we also covered that at the capital markets update briefly, and then, Hal, come back to you in terms of the mRNA approach. Emmanuel, thanks very much for the question. I think as we covered last year that the update. Well, we see flu as a real opportunity area, to be honest. There's significant disease burden, as you well know. But also, when you look at a plot of vaccine efficacy, it's the one area that stands out that's crying out for innovation to move an on average efficacy level of 50% some way higher. I think mRNA is a very exciting technology. It's one that we are investing in significantly. It's one that we think could potentially differentiate as well. I think the opportunity is that differentiation. In our CureVac partnership with Hal, which Hal will go into, we're looking at both flu and also looking at a universal flu option as well. I wouldn't forget egg. Egg is something that's going to be around as a technology for a number of years, and we'll continue to maximize that. We're allocating significant capital into the mRNA play to ensure that we look to differentiate. Obviously, the challenge with mRNA and a multivalent vaccine, which flu is trying to solve this reactogenicity ceiling issue that you can hit with mRNA. I think it's gonna take a little bit of time to optimize any mRNA platform to be able to deliver that as well. Our strategy is clear. Continue to maximize flu in the egg base and develop at pace an mRNA platform that can get us a flu solution to deliver a higher performing flu efficacy. Yeah. Thanks, Roger. Thanks Emmanuel for the question. I think it's pretty clear to the world now that mRNA is a disruptive technology that's really going to transform to some extent how we think about vaccines, both because of its advantage in terms of speed from sequence of a virus or the knowledge of what virus is gonna be endemic at that phase, like in flu. With the longer you have to figure that out, the more likely you are to get the right valence in your vaccine. That'll be a unique opportunity. As alluded to by Roger, the other thing is that if you can have a polyvalent vaccine, the efficacy is likely to go up relative to a monovalent vaccine. mRNA has a significant potential in flu, and we should be in the clinic with a multivalent mRNA vaccine in 2022. We're very proud of that with CureVac. I think the key thing with multivalent vaccines and mRNA is, of course, the more transcript you put into a patient, the risk is higher reactogenicity. Some of that's somewhat solved by modifying the bases. But even with that, as we saw from some of the Moderna data, we're gonna have to continue to work on that. One of the strategies that we're pursuing, that we're excited about is whether we can lower the dose of the transcript by optimizing its stability and how effectively it's translated. In fact, more protein for a given amount of mRNA. We think that the proprietary technology developed by CureVac with this optimization of the codons flanking the transcript, the five-prime and three-prime regions, that were done through some pretty sophisticated machine learning. We think this will allow us to lower the dose, or if you could think of it as keeping the same dose, but with a larger number of valence and both immunogenic and well-tolerated, you know, limited reactogenicity, to be able to develop a best-in-class flu vaccine. Thanks, Hal. I should also mention just for completeness, we'll have two other mRNA vaccines in the clinic this year as well for COVID. At least three mRNA vaccines in 2022. Yeah. Great under new vaccines leadership as well. Yes. Yes. We're confident in that. Thank you. Next question, please. Next one is coming from Jo Walton from Credit Suisse. Please go ahead. Thank you. Hi, Jo. I'm afraid I'm gonna go back to the margin question. On page 24, you tell us that you're gonna have 5%-7% top line growth, 12%-14% adjusted growth, all excluding COVID, and we know that that includes two points from Gilead. On page 36, you tell us that SG&A and R&D are going to go up in line with sales, and it's the COGS that's going to go up less than sales. There's a very big COGS improvement that we should expect in 2022. My question is, if we were, and we obviously don't have this data, to look at just the COGS of new GSK, how far adrift of your peer group do you think you are? So that we can get some guide as to whether the majority of the margin gains that we're expecting, not just in 2022, but in 2023, 2024, et cetera, are going to come from COGS and how much are going to be able to come from a winding down of SG&A. I'm assuming that R&D will continue to grow strongly. Thank you. We said, and we say again, Jo, is that we'd expect to grow SG&A, and this is very much customer-facing SG&A, so it's focused on supporting top-line growth and engagement with patients and customers. If you like, the component that is oriented around functional support still has a trajectory that is flat to down. SG&A, we'd expect to be similar levels, but slightly below revenue growth. The same is true from an R&D perspective. Although it will continue to grow, it's gonna be similar to, but possibly slightly below revenue growth. In terms of productivity coming through cost of goods sold, part of this is driven by top line. We're seeing a change in mix in the portfolio over the period 2022-2026, moving to about 75% of the revenues coming from specialty and vaccines, moving to 25% coming from the general medicine portfolio. That mix change is an important part of the change overall. Now, when you talk about geographic mix, we remain broadly stable to where we are. We've got about 40% for revenues in the U.S. now. By 2026, we'd expect about 40% for revenues to be U.S. as well from biopharma perspective. That change in mix of new, especially medicines and vaccines to 75% versus 25% is an important component of the overall gross margin story, notwithstanding the continued delivery of productivity and synergies coming through the supply chain. Those are key dynamics that are coming through there. We're also having a bit of a one-year recovery of COVID T&A. I mean, I know we're keeping costs very much under control on that, but we are expecting to go back a little bit. Absolutely, but very much within the guidance that we've provided today, Emma. Yeah. Okay. Next question, please. Next one is coming from the line of Steve Scala from Cowen. Please go ahead. Thank you very much. It looks as though the contRAst-1, 2, and 3 trials of otilimab are well past their primary completions. They have conventional endpoints, so there's no events to wait for. Is the data in-house? Hal, I have to say, you do sound more confident today than you've been in the past. Is there a delay? Why won't the filing be earlier than 2023? Thank you. Thanks, Steve. No, I have not seen the data. I'd love to see the data, but I have not. The reason is, and you're absolutely right, that it's a 12-week endpoint. It's not event-driven, so that shouldn't be the problem. The issue is the data remains blinded with all these studies for the 52-week follow-up because of the interest in secondary endpoints of having the active recruitment phase of the program. In order to maintain the integrity of the trial, it's blinded for a longer period of time. Next question, please. Next question is coming from the line of Andrew Baum from Citi. Please go ahead. Andrew? Thank you. A question on BCMA. Two parts. Firstly, DREAMM-5. Yep, can you hear me? Yeah, we can hear you. Can you hear me now? Yes, I am. Hello? Right, Andrew, we can hear you. Can you hear me? Yep. Hello? Right. Terrific. Yeah. Okay. Go on. Terrific. I can hear you too. Here we go. The question's on BCMA and DREAMM-5 with the gamma-secretase, and you recently expanded that cohort. It's an open-label trial. GSK has of late talked more about scheduling dose fractionation and less focus on the benefits of GSI. Given that it's open-label, given you've expanded the cohort, perhaps you could share what you're seeing. Then secondly, also on BCMA, there's been some recent data published with a CAR T suggesting that BCMA CAR Ts were associated with Parkinson's-type syndrome due to BCMA expression on substantia nigra. The question is, do you have any evidence that belantamab crosses the blood-brain barrier? I'll stop there. Thank you. All right, Dr. Hal. Well, thanks, Andrew. Let me try to address that. It's a really interesting question about the Parkinson's. We have no evidence to suggest, and I'm reasonably confident that it doesn't, the antibody crosses the blood-brain barrier. So to the extent that it is a non-target effect, we're not observing that clinically, and I wouldn't expect us to. I can look into a little bit more detail about that later, but I'm pretty confident it's not crossing the blood-brain barrier. It's an interesting point you make about the CARs. As you know, the rationale for the combination of the GSI with belantamab was that it should be able to increase the density of BCMA on the plasma cells, or maybe any cell, but the plasma cell is of interest, and therefore be able to obtain responses at lower doses. We hope that at lower doses, there'd be less ocular toxicity. It's one of the four levers that we're using to try to improve the benefit-risk ratio, and I'll go into the other three in a second. We have seen some open-label data and as we said, it is encouraging. It's small numbers, and I think we've all seen examples where small numbers of encouraging data doesn't always translate. The data was definitely encouraging enough that we moved into a randomized setting, so using the DREAMM-5 platform to begin a more robust program where we both have larger number of patients, but also a control arm to make sure that it's not confounded by baseline covariates that can occasionally happen. I can say that our optimism was based on seeing data, and we, as you know, we're using doses at the 0.92 milligrams per kilogram level, which at least in the DREAMM-1 and DREAMM-2 studies was inactive. We think that that's a reasonable way of assessing our level of optimism. Mid-year this year, we should have a much more robust data set, hopefully with some control patients and be able to be clear with the value that this could provide to move into frontline. As you know, the other three levers that we're looking at to optimize this program are to see if the combination of BLENREP with standard of care, whether it be, you know, with pomalidomide or Darzalex or Velcade or various other standard of care regimens, would allow us to be able to reduce the dose to further maximize its benefit risk. We're also looking at something relatively simple, which is in the phase pivotal DREAMM-2 study, the protocol had dose holding when grade 3 ocular tox was identified. For the ability to reduce grade 3 and above ocular toxicity is limited if that's when you hold the dose. Given the profound efficacy that we're observing in multiple different trials now, we've decided to hold the dose when we're seeing grade 2 ocular tox, which in theory and actually observed data from Ash suggests that the ocular tox is going down further. And maybe even the most important of all these, who knows, is going to be that we're altering and exploring different schedules. As you know, in DREAMM-2 and the approved dose for fourth-line and later therapy was using 2.5 mg/kg q3 weeks. We're looking at q4, q6, and even q8 dosing at doses of 2.5, 1.9, and even lower. Seeing if Cmax versus trough is going to have an impact on both efficacy and hopefully reduce ocular tox. Those four levers, if you will, all being studied independently and the ability to use them as modules and combine them to move us into third, second, which we're reasonably confident in, and maybe even frontline. We'll have data mid-year to help you understand that. Thanks. Next question, please. Next one is coming from Laura Sutcliffe from UBS. Please go ahead. Hello. Thank you. Could we go back to HIV, please? There's been some commentary in recent days from Gilead talking about a tougher first quarter 2022 than 2021 based on co-pay scheme resets in the U.S. and other gross-to-net dynamics. Is there anything we should be thinking about along those lines, for your portfolio in terms of it being more aggressive this year than it was last year? Just related, given the wider importance of the access to medicines piece at group level, is there anything you see changing on your ESG profile or external rankings, whichever ones you consider to be most meaningful, when Consumer leaves the group later this year? Thanks. Thanks. Well, on the broader ESG, and then we'll come to Deborah, you will see us continuing to seek to make leadership in ESG a priority for GSK, and we will be updating our reporting on that, frankly, to make it ever simpler, more transparent, and easier for us to be held to account across the six key areas we've identified as priority for ESG, whether that be, you know, in access, in environment, in diversity, and inclusion. We're really looking forward to discussing that with you. You'll also be familiar with the fact that it is at a focus level that's included in the accountabilities from an incentive point of view as well. It really is something that has long been at the core of who we are as a company. It never replaces TSR, but I'm hoping that we are able to continue to get the recognition for our very much leading rankings we have, but also transparency and simplicity of reporting in a way that is, of course, validated by third parties, as opposed to us just marking our own homework. Maybe come back to Deborah, please, for the HIV question. Thanks, Laura. If I think about the PrEP market and treatment as two separate markets. In the treatment market, it continues to be guideline-driven. Choice and access are absolutely crucial, and we see that market as, you know, as continuing to be relatively stable. Obviously, the Build Back Better bill, you know, will affect the whole industry. Let's see how that plays out. In terms of what, you know, if you assume that's taken to one side, the treatment market looks, you know, fairly stable and continues to be guideline-driven with choice and access as the core. In the PrEP market, it's a little bit different to that. Obviously, you've got a generic of Truvada in the market. Gilead have moved quite a lot of the market away from Truvada into Descovy. I think that's taken, you know, obviously, some negotiation with payers to make that happen. We're in dialogue with payers at the moment over ensuring that we can get broad access to Apretude at a price that rewards our innovation. I think you should look at treatment and PrEP as a little bit separate. In the main, you know, the treatment market is five times bigger than the PrEP market. The core of where our revenue and our profit comes from remains stable. The other core is having truly differentiated medicines and medicines that get approved and stopped in their trials for being so significantly better than existing standard of care. It deliver a value that is worth paying for. Absolutely. Next question, please. Next one is coming from the line of Seamus Fernandez from Guggenheim. Please go ahead. Oh, thanks very much. My question is actually on HBV. Just wanted, Hal, if you could give us your thoughts on the HBV ASO versus antibody-based approaches. As well as just your general thoughts on how we're likely to ultimately see a real break in HBV cures. Is that gonna require a combination of a treatment-based approach followed by a vaccine in your view? Or when we see these data later this year, do you think that either an ASO or perhaps RNAi-based approach will really be viewed as the preferred way to then pursue cures? Thanks. Yeah. Thanks for the question. It's a really good question. You know, it's really hard to predict the future on this, but it is likely that what we'll see with the ASOs is a couple things. First, I think it's pretty clear that not all S-ASOs are behaving the same way. I think over the next 6-12 months, we'll get more clarity on the value of the various approaches of ASOs, GalNAc or unmodified. I think we'll get a good sense, and I'm optimistic from our 2A data that the ASO approach will deliver efficacy as it relates to lowering the surface antigen. One of the hypotheses is that this, you know, this virus makes a massive amount of surface antigen, and one compelling hypothesis that's pretty well supported from preclinical data is that that overwhelms the T cell, and it results in T cell exhaustion. That by lowering the HBV surface antigen levels, the immune system may be able to kick in. My guess is that that will work in some people, but probably a very small minority, and what's gonna be needed is combinations. Whether that's a combination with a nuke interferon or possibly even something like a checkpoint blockade like PD-1 or maybe even a STING agonist, things that are going to increase the interferon production from the Kupffer cells and other cells responsible for the immune. I do think, though, that in the end, after we figure all this out, and hopefully we'll have some compelling data midyear with the B-Clear study, that we'll be able to embark on these combination studies in a thoughtful manner and ultimately reduce the really enormous burden of 250 million people living with chronic HBV. As I mentioned, 900,000 people dying from it annually. If we can make a dent in the functional cure rate, which is a very high bar, that will be one of the more significant advances in medicine. Thanks. Next question, please. Next one is coming from the line of Kerry Holford from Berenberg. Please go ahead. Thank you. Just to follow up on RSV of older adults, please. Hal, you mentioned targeting the June ACIP meeting. I guess you're working on the assumption of a launch next year. I would just like to understand what gives you the confidence that the regulators accept a data package from one RSV season only, given your and competitor studies will continue further. Is there a risk that the regulators want to see more data across more seasons before moving to approve a vaccine here? Do you think that decision will ultimately be influenced by the clinical efficacy you and your peers deliver? Thank you. Thanks, Kerry. I think we're pretty confident in our strategy, but of course, any approval and any recommendation for use is gonna depend on the risk-benefit. We're, you know, expecting a reasonably high success rate and effectiveness rate for this vaccine, and being able to show it works well in the various subgroups of interest, as well as determining whether this is going to be effective in an equally significant way across the season. In other words, how effective the duration of efficacy relates. When we have all that data, I think we'll be able to have a better sense, but we're pretty confident in our strategy of the trial design, the sample size, the effect rate, and the risk benefit that that would endure. I should also mention that, of course, that the ASO is something that we have enormous amount of experience with and a very, very large safety database with. It's really gonna be driven by the efficacy and probably viewed by ACIP in aggregate all the data as well as how the regulators will view each individual company. Thanks. Next question, please. Question is coming from the line of Mark Purcell from Morgan Stanley. Please go ahead. Yeah. Thank you for taking my questions. Just again on RSV older adults and getting a bit more perspective, I wonder if you could sort of help us understand how we can assess whether the AS01 adjuvant will provide a potential durability advantage from the initial datasets, your own datasets, Renoir and Evergreen. You know, what should we be looking out for which suggests you might have a sort of T cell restoration benefit? And then just a related question. Are there any IP considerations around the pre-fusion F subunit target? You know, clearly you were a first mover when it came to HPV, and you secured a royalty stream. Is there something such that we should think that that situation could occur with RSV? Yeah. Thanks, Mark. Why don't I tackle the first part? I don't think there's any IP issues that we're unaware of, but I'll let Roger jump in if he knows of something I don't. I think it's gonna be challenging to figure out the impact of the adjuvant on duration as it relates to multi-year because, of course, point-in-time blind, we won't have multi-year. In fact, when you look at Shingrix, it obviously took eight years to figure out that it worked so well for eight years. I do think there is going to be hints potentially one could look for. It'd be underpowered for these, but I think they might be directionally useful. First of all, is the point estimate of benefit greater than other trials? I think that's one thing to look for that would suggest that the adjuvant is doing something unique. It could also be that in subgroups, particularly the older 75 and the particularly immunosuppressed patients, one might see a signal that looks more prominent than non-adjuvanted. That might give you a signal. As I said a few minutes ago, there is a way of looking at the duration of efficacy as of the season. If the efficacy with a non-adjuvanted vaccine, for instance, is pretty significant in the beginning of the season, but wanes during the end of the season, and for instance, ours would have a treatment effect that's impressive and constant over that period of time, one might be more confident that there could be a duration effect when one looks longer. At the end of the day, we're going to have to look for a longer-term follow-up. We have studies already underway that I'll explore. Roger, did you want to add anything? Yeah, just on the IP. There's no IP restrictions on the PreF, nor is there any IP direct ownership from our perspective that would generate income. That's not something that we should be thinking of worrying about. Okay. Not sure. I think we've got time to go through one more question, and we have one more question. I'm sure maybe Brian. Yes, we do. Our last question for today's call comes from Peter Welford from Jefferies. Please proceed. Oh, hi. Thanks for squeezing me in. Just a question just on RSV vaccine again in the older adults. Can I just ask, when we think about the COVID data, have we all been spoiled to the hospitalization and decreases that we saw there of 90% plus in some cases? Perhaps could you give us some sort of idea of what we should be thinking about for the RSV phase III with regards to what is a reasonable reduction in hospitalization? You know, is it in the nirsevimab 80% or so reduction, a sensible sort of ballpark that we should regard as clinically meaningful. And perhaps just a comment, I think you probably should win an award for sort of the master of understatement. From my calculations, it seems as though your strong double-digit growth is probably over 40% for Shingrix. Can you just remind us if the GBP 2.5 billion, if that's roughly where I get to from your guidance, is entirely can be met with existing manufacturing? Should we then consider future growth from that? Again, are you confident that you can sustain that level of growth and that level of demand with your existing capacity that you have without the need to deliver? Thank you. Let me be extremely utterly unequivocal. We are not supply constrained, and we're very confident on doubling our Shingrix sales from those 2020 levels in terms of the outlook that we gave in at the update last year. We feel very good about getting a bounce back. Obviously, there's been a bit of COVID disruption, but as Luke outlined, the momentum is very good. I don't know how if there's anything further we want to add. No, I'll just say that, you know, of course, it's very hard to predict the efficacy. But as we look at our own immunogenicity data and the aggregate packages that have been presented, I think and in discussions with clinicians, we're pretty confident that any effect more than 50% is clinically meaningful. An effect greater than 70% is a very good response, and it'll be a very successful vaccine. Should we get efficacy above 80%, you know, that's outstanding. Great. Well, with that, thank you very much, everybody. We shall look forward to gathering with some of you over the next few days. We're really looking forward to an extremely exciting year ahead for GSK. Whether that's doing everything that we said we were going to do, the delivery of the step change in growth, reading out on some of these very exciting pipeline milestones, continuing to accelerate the execution of all that we already have at hand and plan for very competitive execution of what's to come, and of course, the tremendous unlock of value that's going to come with the creation of a completely unique FTSE leading world leader dedicated to consumer healthcare. I know Brian is enormously looking forward to the long Q&A session on that at the end of this month. Thanks, everybody. Catch up soon.