Good morning and good afternoon. I'm Iain Mackay, CFO of GSK, and it's my pleasure to welcome you to our investor update. We have a packed agenda, which I'll detail in just a minute. However, before I do that, I'd like to mention a couple of housekeeping details. First, you should have received our press release, and you can view the presentation on GSK's website. For those not able to view the webcast, the slides that accompany today's event are located on the investor section of the GSK website. Second, during the question and answer session, we would ask that you limit your questions to two so that everyone has a chance to participate. Before I begin, please refer to slide two of our presentation for our cautionary statements, and our basis of preparation can be found in the appendix. With that, we'll move to slide three, and let me take you briefly through our agenda. Our speakers today are Emma Walmsley, Luke Miels, Dr. Hal Barron, Deborah Waterhouse, Dr. Kimberly Smith, myself, and Roger Connor, who is joining us via video as he's been tracked and traced by the NHS and is in his last day of self-isolation. Emma will open the event outlining the strategic transformation, outlook, and ambitions for New GSK. Luke and Hal will then present an overview of the progress we've made in commercial and R&D and how this will support delivery of growth over the next decade. We'll then head into a series of deep dive sessions on vaccines with Roger and Hal, our HIV therapy area with Deborah and Kim, and other key high-potential specialty pipeline assets with Luke and Hal. I'll set out our details on our financial outlooks, capital allocation, and dividend policy, as well as details on separation of Consumer Healthcare before we close and move to Q&A. Our presentation will last for about two and a half hours, there'll be a refreshment break halfway through. With that, I hand over to Emma. Thank you, and a very warm welcome from me to our investor update. During the course of today, we will set out clearly why post-separation of our consumer business, New GSK will be a growth company able to create significant value for patients and shareholders from 2022 and for the next decade. You'll hear about competitive performance. Over the next five years, with 2021 as a base year, we expect to deliver highly attractive growth with sales and adjusted operating profit of more than 5% and more than 10% respectively on a compound basis. These are new commitments and a clear step change in performance from GSK. We are confident we can deliver. This growth will be accompanied by a new progressive dividend policy. We expect New GSK's annual dividends to start at GBP 0.45 per share in 2023. Iain will walk through more details of expected dividends, including for next year later on. By 2031, we aim to achieve sales of more than GBP 33 billion. This ambition is driven by our current late-stage pipeline and is before any significant sales contribution from our early-stage pipeline or any contribution from future business development. Our late-stage pipeline has the potential to deliver over GBP 20 billion in non-risk adjusted peak year sales, supporting our confidence in these revenue expectations. Very importantly, this sees New GSK growing through the decade despite the anticipated loss of exclusivity for dolutegravir. New GSK will prioritize innovation in vaccines and specialty medicines, maximizing opportunities that are increasingly evident across prevention and treatment of disease. We will support investments in innovation through the attractive profitability and cash flow of our general medicines business, which we expect to continue to optimize. New GSK will benefit from a strengthened balance sheet after the separation of consumer healthcare, also enabling us to pursue a growth-oriented capital allocation policy. We will deliver this performance while meeting the high standards expected of us, retaining leading-edge ESG performance and driving a culture of ambition, accountability, and responsibility. This is the New GSK, one that is ambitious for patients and for shareholders, a new company with a strong focus on delivering improved performance, shareholder value, and positively impacting the health of more than 2.5 billion people over the next 10 years. Alongside the right strategy and level of ambition, of course, what matters is having the right people to deliver, and I am delighted with the transformed strength and depth of leadership all across GSK. You're going to hear from several of these exceptional leaders today. My team is talented, accountable, energized, and empowered to deliver our growth ambitions together. Now, before we get into why we are confident about the future growth of GSK and why we think we will create significant shareholder value over the coming decade I want to spend a few minutes focusing on what has been achieved over the last four years and how this creates a completely different platform for growth. Since 2017, we have undertaken an enormous amount of work to fix long-standing issues across the company, which have been a direct cause of historic underperformance and negative impact to total shareholder returns. Our focus has been to improve R&D productivity, commercial execution, group structure, and capital allocation, and very importantly, drive a new culture with new leadership for more accountability, ambition, and delivery. We've done this by prioritizing innovation, performance, and trust across the entire company, driving a significant and sustained multi-year program of strategic transformation and investment. The scale of the changes made in the last four years is unprecedented, and we've made enormous progress on multiple fronts to improve performance, strengthen capabilities, and prepare GSK for a new future. Our sales and cash flow performance has improved despite the loss of a multi-billion-pound Advair for generics, and we've maintained operating profit levels while making much needed increases in R&D investment. This investment, up 30% over the period, and Hal's leadership have substantially strengthened our R&D performance and productivity. Since 2017, we've delivered 11 major product approvals, a top quartile performance, and doubled the number of assets in phase III and registration to 22. We now have a pipeline of 20 vaccines and 42 medicines, many of which are potential best or first in class. Commercial execution has been transformed by Luke and Deborah. New and specialty product sales have reached GBP 10 billion, growing double digits, vaccines revenues have increased 35% since 2017 under Roger's leadership. We've made significant changes to our portfolio and our network, driving changes to our business mix, reducing our footprint, streamlining our supply chain, achieving annual savings in excess of projections, and divesting non-core brands. Work on all of these continues as we look for further ways to optimize and deliver value to our shareholders. We've created an outstanding new world-leading consumer healthcare business of scale following two successful global mergers and integrations with a radically transformed portfolio and with profit nearly doubled to sector leading levels over the period. We've maintained our acknowledged leadership in ESG, delivering new commitments and progress in all areas of ESG. Powering it all has been a new culture for more accountability and more ambition, underpinned by the integrity and the humanity that GSK is known for. This change has started at the top, where we've transformed our leadership. 85% of our top 125 leaders are new in role since 2017, including 30% recruited externally. The change has been driven across the entire company with new people, new incentives, and new governance. We are now ready to deliver the most significant corporate change seen for GSK in more than 20 years to separate and create a New GSK and new Consumer Healthcare, each with their own appropriately skilled independent boards. Both these businesses will have scale impact on human health and the opportunity to deliver compelling performance and attractive returns for shareholders. With the separation, we will create a new world leader in consumer healthcare, a GBP 130 billion market with very favorable dynamics for consistent future growth. Expertly built and integrated by Brian McNamara and his team, this business will serve 100 markets with a portfolio generating annual sales of more than GBP 10 billion. It will be driven by brands and innovation with leading-edge science and human understanding to deliver better everyday health. With nine global power brands holding category leadership positions, a major sales presence in the U.S. and China, and 11 other brands each generating more than GBP 100 million in sales, this business is well-placed to address consumer needs and achieve future revenue ambitions. It will also have industry-leading operating margins, offering tremendous prospects for profit growth, cash generation, and sustainable returns for shareholders. A comprehensive update on its prospects is planned for investors in the first half of 2022. The separation will take place in the middle of next year. The board has reviewed multiple separation options, always with a lens of unlocking the potential of both businesses, strengthening New GSK's balance sheet, and of course, maximizing shareholder value. On this basis, the separation will take the form of a demerger of at least 80% of GSK's holding to shareholders. New GSK will retain up to 20% as a short-term financial investment, which will be monetized in a timely manner to further strengthen the balance sheet. The demerger is intended to be tax efficient for shareholders as compared to alternative separation options, which has been an important consideration and will be subject to shareholder approval. Iain is going to provide more details on all of this and New GSK's balance sheet later on. Turning now to New GSK. With New ambition comes New purpose. For New GSK, this is to unite science, talent, and technology to get ahead of disease together, all with a clear ambition of delivering human health impact, stronger and more sustainable shareholder returns, and as a New GSK, where outstanding people thrive. Getting ahead means preventing disease as well as treating it. It means innovating together, fusing ideas, capabilities, and know-how inside and outside of GSK. Our R&D focus is to deliver new vaccines and medicines using the science of the immune system, human genetics, and advanced technologies, and together with a deep commitment to operating responsibly for all our stakeholders. We also remain committed to getting ahead of issues that matter for the sustainability of our company, be it pricing and access, the environment, or stronger diversity and inclusion. How we do all this is through our people and our culture, a culture that's ambitious for patients, accountable for impact, and committed to doing the right thing. We deliver what matters better and faster, to have clear ownership for goals and the support needed to succeed, and always with integrity and care. Our ambitions are reflected in these new commitments to growth that we're making today. Both of these goals represent significant step changes in delivery. In the next five years, we expect to deliver more than 5% sales and more than 10% adjusted operating profit growth on a compounded basis. By 2031, we aim to deliver more than GBP 33 billion in sales. We have clear metrics in place and incentives at company and individual levels to drive performance in-year and over these time frames. Existing incentive measures include delivery of innovation sales, pipeline progress, operational performance, and relative total shareholder returns. Performance targets and reward are strongly aligned to shareholder interests and shareholder value creation and will be for New GSK. I am very aware that GSK shares have underperformed for a long period. The transformation achieved over the last four years creates a completely different platform for growth and significant shareholder value. One that will move GSK from historical underperformance to a new, ambitious top-quartile growth outlook and delivery. To drive our step change in growth, we will continue to prioritize investment to vaccines and specialty medicines, which we expect to grow to around three-quarters of our revenue base by 2026. Over the next five years, in CAGR terms, we expect sales to grow at high single digits for vaccines and double digits for specialty medicines. Our newly defined General Medicines Business will contain all our primary care brands, we'll optimize this business for profitability and cash flow. As we've done in the last four years, we'll continue to look for opportunities to streamline the portfolio and maximize its value for shareholders. With the plans we have in place, we expect general medicine sales to be broadly stable over the next five years, which is a significant change from the recent dynamic. A key reason for prioritizing investment to vaccines and specialty medicines is to realize the increasing opportunities now being seen across prevention and treatment. Our understanding of the relevance of the science of the immune system continues to grow, and modalities are converging. We have the approach, the tools, the portfolio, and the capabilities to deliver growth and value here. Investment and resource allocation to vaccines and specialty medicines are focused across four core therapy areas: infectious diseases, HIV, oncology, and immunology, including respiratory. In each of these areas, there are major unmet patient needs and significant opportunities for growth. Agility is also important, and we'll pursue great opportunities in organic research and in business development consistent with the science of the immune system and human genetic validation. This we describe here as opportunity-driven. Each of these therapy areas contain marketed key growth drivers and promising late-stage pipeline candidates. Together, they will deliver strong growth over the next decade. The next five years will see us building on the momentum we have delivered to date, and we expect growth to be increasingly supplemented by contributions from late-stage pipeline assets. The potential of these late-stage assets is significant. On a non-risk adjusted basis, they have the potential to deliver peak year sales of more than GBP 20 billion. The major contributions to our top-line ambitions are summarized here. Of course, alongside expected positive contributions from key assets are generic expirations. From 2021 to 2026, New GSK's loss of exclusivity exposure is negligible and compares very favorably to peers. As can be seen here, our next major anticipated loss of exclusivity comes with the patent expiry of dolutegravir in 2028 in the U.S. and 2029 in Europe. Deborah will come on to explain the transition we expect to see in our HIV portfolio to long-acting medicines. This significantly reduces our exposure to genericization and supports profitable revenue renewal in our HIV portfolio. Importantly, at a company level, we expect the loss of dolutegravir to be more than offset by the expected sales contribution from the late-stage pipeline. From 2026 to 2031, growth will be driven by executing on these late-stage assets, through which we aim to achieve at a minimum GBP 33 billion in sales. I repeat, we do not include any significant contribution from the early-stage pipeline or any contribution from future business development, which of course, we will continue to pursue. I should also be clear that these outlets do not include any revenues or profits from COVID-19 solutions. We will leverage top-line growth to drive meaningful margin expansion. We expect to drive our adjusted operating profit margin from the mid-20s level currently to over 30% by 2026, so that we deliver double-digit compounded profit growth over the period. We now expect to achieve £1 billion of annual savings from our Future Ready program by 2023, a £200 million uplift from our previous estimate. We're therefore revising our combined total for programs to £1.5 billion of savings. Approximately a third of total savings are being reinvested to drive growth in the business, with the remainder expected to drop through to the bottom line. These programs are expected to complete in 2022, and no further major restructuring programs are planned, but our focus on driving out cost will continue. This will include more R&D productivity initiatives, further streamlining our manufacturing network, embedding new ways of working with pandemic learnings, and disciplined prioritization of projects with the highest returns. Of course, another very important driver of margin expansion will be the change we drive in sales mix towards higher margin vaccines and specialty medicines. Turning now to capital allocation priorities. Our first priority will still be to invest in our pipeline, including with business development activity with a focus on bolt-on acquisitions and in-licensing deals. We will strengthen our balance sheet with the separation and with the strong operating cash flow we expect in the coming years. By 2026, we expect cash generated from operations to exceed GBP 10 billion. This will allow us to focus capital deployment on supporting growth. We will support successful product launches. We'll continue to improve the sustainability of our operations, including reducing our carbon footprint. Of course, we intend to deliver attractive and growing returns to shareholders through our progressive dividend policy. For New GSK, ESG will continue to be an integral part of our strategy and our investment case, and it will be a key driver in our goal to deliver health impact and shareholder returns, as well as being core to the motivation of our people. We will pursue a focused approach to ESG driven by our strengths, informing our strategy and addressing the key challenges of our industry over the long term. We'll prioritize our resources around the six areas you see here, which we see as material for our business and sit across E, S, and G. Accountabilities for each of these six sit with respective members of my leadership team. For New GSK, we expect to strengthen the alignment of remuneration to delivery of ESG performance and increase the visibility of this for investors in our reporting. We'll also continue to report against a set of public trust commitments. We believe our approach to ESG will support delivery of sustainable performance and long-term growth, build trust with all our stakeholders, reduce risk to our operations, and enable delivery of very positive social impact. In line with New GSK's purpose, a defining measure of success will be this health impact at scale. Our plan shows that New GSK can positively impact the health of more than 2.5 billion people over the next 10 years, with the company making meaningful contributions in all parts of the world, protecting people and helping them fight disease. New GSK has new ambitions for patients and for shareholders. The team you will hear more from today have been leading our extraordinary program of change, and we are now ready to take New GSK forward into a new decade of growth and impact together. Let's start by hearing from Luke and Hal on how we deliver. Thank you, Emma. The aim of this part of the presentation today is to give you the confidence that the commercial organization can deliver a CAGR above 5% from 2021 to 2026. Over the next few slides, I'll outline the changes that we've made to people, products, and processes since 2017, provide you with depth at the operating level on our execution in specialty and vaccines, and then give you color into the way we will optimize our general medicines business. Finally demonstrate how we've established a highly effective partnership between commercial and R&D that will set us up to deliver our ambition of more than GBP 33 billion in sales by 2031. Throughout, I'll provide the numerical evidence of our progress. This slide outlines the path for us to get there at a product level. Our sales ambitions to 2026 and beyond are underpinned by strong execution against key in-market assets and our ability to deliver and unlock the value of our pipeline. You'll hear from Roger and Deborah about our growth drivers in vaccines and HIV, and then Hal and I will cover our other specialty opportunities, including a review of the late-stage pipeline assets. This is the framework we've used since 2017 to improve our ability to compete in the market. You can see there are three main phases to this, and it remains a work in progress. Phase I was essentially about getting the right people in the right jobs, fixing how we operate, and then sorting out the cost base. In phase II, the focus is on finding ways to maximize the growth in existing products and markets. Phase III is about working very closely with Hal and his team in R&D to maximize the value of the pipeline. On this slide, I've shared some of the examples of what phase I means and what's been executed. The first order of business, of course, was to appoint the right leaders across the markets and in key global roles. We've appointed new general managers in 64 countries, which drive over 90% of our sales today. For these important roles, we have a very specific phenotype. Each of these new leaders have then driven change deeper into their respective organizations. The next priority was to rebuild the commercial team who interact directly with R&D to select and develop the pipeline assets. These people, if they provide the right commercial input at this point, can create enormous multi-year value, and we want the best and the brightest in these roles. From 2017, a two to three-year rotation in this team was made mandatory prior to appointment as a first-time general manager. Their time in role at headquarters is capped so they don't become permanent residents. Success here, not only in fluency with working with R&D, but a fast track to larger commercial roles. This ensures we get the best people. The overall dynamic that our people operate in with our peers in R&D is strong because Hal and I like working together. We also strengthened our marketing and medical capability in specialty medicines by hiring over 900 people with the right expertise to compete. In parallel, we took a very critical look at our footprint and reduced our direct presence from 140 markets to 70, while further concentrating our investment in the top 10 markets, which drive the bulk of our growth. Another key driver to rightsizing the organization was to reduce our back-office costs, which we did by significantly reducing our non-customer facing commercial infrastructure and reallocating the savings to high-growth markets and specialty products. In bringing our policies to par with industry best practice, this has further allowed us to improve our competitiveness while maintaining trust. Combined, these changes have enabled us to establish an organization that is pointing the right way, knows how to launch a specialty, and can thrive with complex products. In phase II, our focus moved to product strategy and the translation of this on the ground. Starting with a back to basics approach, the changes we made at the leadership level, coupled with strong marketing, medical, and sales force collaboration, have resulted in measurable improvement in our sales force effectiveness and productivity across key markets. As you would expect, we track and assess this progress via third-party audits across our markets. The audits of actual rep and doctor face-to-face interactions seek to determine if a call is effective by stratifying in a manner which is correlated with changes in prescribing behavior. Taking Nucala as a representative example, you can see in this data set that we've delivered material improvements in good selling outcomes where the change in customer's behavior is agreed. This is the outcome with the highest correlation with a positive change in prescriptions, and this positive trend is also demonstrated across our other key brands. For example, in the U.S., Trelegy went from 22% good selling outcomes in 2018 to 30% in 2020. Now we placed these audits on hold when COVID hit face-to-face interactions in the field. Now that the reps are going back into the field in the U.S., we will restart these audits, and we've just run our first wave, in this case with BENLYSTA, and the new data showed that we have moved from 16% in 2018 to 25%, which is above the industry top quartile. Now STEM data is a measure of quality, and we remain disciplined and focused on continuing to become more competitive in our face-to-face interactions. However, the number of face-to-face sales calls and medical interactions collapsed from early 2020. This disruption presented us with an opportunity to accelerate several initiatives in digital and predictive analytics. Rapid execution of these initiatives, combined with an immediate shift to virtual activities by our customer-facing teams, have enabled us to maintain a leading share of voice where we compete, as shown in the third-party tracking data on the left-hand side of the slide. In the middle panel, you can see the impact on new prescriptions when a data-driven customer experience is adopted on top of the traditional field force activity. For example, when we applied this to Trelegy field promotion in the U.S., we saw a 47% increase in prescriptions. On the right, in lupus, we deployed a machine learning algorithm which processed in total over four billion terabytes of data, including claims and diagnosis codes. For this, we concentrated on three distinct areas where there was a gap to treatment and have directed our medical efforts to address these. Agility is important here. We encourage a decentralized approach to innovation in our operations, but when we see something that works, we adopt a centralizing mindset and drive that execution across the markets. All of these elements give us the confidence that we can make the scientific case for our products across multiple therapy areas. One more key measure to gauge effective execution is how quickly a business can mobilize following regulatory approval. It's a good indicator by its nature, as it's a complex undertaking involving a spectrum of cross-functional activities, ranging from packaging and supply at one end, all the way to pricing and reimbursement and training. Competitive pace here requires a team on the ground to have clarity of purpose, alignment, and thoroughness driven by a commitment to getting the product to patients in the best possible timeframe. In 2013, it took the team in the U.S. five months for Breo. In 2020, it took our new team five hours for Blenrep. Pulling these elements together has resulted in better commercial outcomes across therapy areas and in diverse scenarios. For example, in the case of launching products, you can see here that Trelegy had the best launch of an inhaled respiratory product in 10 years and continues to lead in total prescription and new patient starts in this highly competitive disease area. We've also demonstrated that we can launch well into new therapy areas for GSK, as shown here with Blenrep, which despite a complex REMS program and a challenging environment, had sales surpassing key competitors in late-line multiple myeloma within the first quarter. With SHINGRIX, we demonstrated the ability to fully utilize a compelling product profile to disrupt and then rapidly expand what was relatively a modest and stable established market. As I said earlier, we have also been able to deliver better outcomes in diverse scenarios. The performance of ZEJULA following the Tesaro deal is a fair demonstration of this in my mind. On acquiring ZEJULA, we inherited an existing oncology commercial infrastructure and a product with an established profile in the eyes of many doctors. We saw an opportunity to reposition the product and improve execution on the ground in one of the most competitive areas in oncology. On this basis, we overhauled the entire commercial and medical approach, and this placed us in a good position following a readout of the PRIMA first-line ovarian cancer study. ZEJULA is now on track to be the most prescribed part in first-line ovarian cancer, with leading new patient share in both the U.S. and EU. Now, we've also worked hard during this second phase of change to create more opportunities for growth in parts of the portfolio which are at the midpoint of their life cycle. For Bexsero, we redoubled our efforts to educate physicians and parents about the devastating impact of MenB and the strong protection that they can expect from our vaccine, supported by newly available real-world evidence. We also invested more in the U.S. with a new campaign. This led to an increase in market share, with market share moving from 65% in 2017 up to 73% now. While COVID impacted performance in 2020, the strong fundamentals and large cohorts of children and adolescents who would benefit from MenB protection point to recovery and growth. On the right-hand side is BENLYSTA, which prior to 2018 had relatively limited investment. We changed our strategy in the markets and repositioned the product, resulting in a 24% CAGR in the last three years. The recent launch in lupus nephritis further increases our growth potential and is more proof that specialty medicines with a good life cycle management can deliver many years of strong growth beyond their initial launch. The examples over the last few slides demonstrate that we are now more effective as an organization at translating the science behind our products into appealing patient and commercial outcomes. Now looking forward, we're very clear in our areas of focus, as you've heard from Emma. We expect New GSK growth to be driven by vaccines and specialty medicines, underpinned by a highly profitable and resilient general medicines business. We're confident that this combination of existing and new assets can deliver greater than 5% sales CAGR between 2021 and 2026. Over the next few slides, and again later with Hal, I'll seek to add some color to this projection. Firstly, with SHINGRIX, we expect it to be the number one driver for our growth in the vaccine portfolio over the next five years. As you'd expect, our focus right now is to relaunch the product following the rollout of the COVID vaccine programs, which necessarily disrupted normal vaccination schedules. We're taking steps to ensure that we reach patients by activating a range of activities, and we're generating data both on the impact of COVID on shingles and on safe co-administration with COVID vaccines. This should all read out in Q4 this year. Market research conducted in April indicates that almost 60% of individuals intending to get both the COVID and the shingles vaccine plan to do so within three months of their COVID shot. We're also seeing very encouraging signs of a recovery of prescriptions, which are now up to nearly 69,000 in the most recent weekly NRx data, approximately double the numbers that we saw in mid-March and April when the COVID vaccine campaign took off. The recent ACIP recommendation on adult vaccinations gives us further confidence that the market will rebound. Looking beyond the pandemic, we have a multi-pronged strategy which will enable us to fully capitalize on the huge potential of SHINGRIX. This includes addressing the large population of unvaccinated individuals in the U.S., driving growth in China, and launching in new geographic markets on top of lifecycle innovation. Geographically, as expected, the U.S. is central to this overall growth ambition as it accounts for more than 40% of New GSK sales. It will remain our most important market as we concentrate the bulk of our effort on vaccines and specialty medicines. From 2021 to 2026, a large component of our growth will come from our frontline in-line products, including SHINGRIX and Juluca, as well as the evolving HIV portfolio, which Deborah will cover later. We are also preparing the organization to compete in the next wave of launches, notably our new vaccine to prevent RSV, which from a revenue perspective, has a similar potential to SHINGRIX in the U.S. and globally. For China, execution will be key to achieve our growth ambition, particularly with vaccines. We are pleased with the opportunity we have with Cervarix. The government has an Expanded Program on Immunization, which focuses on 12 preventable diseases through routine immunization. In 2020, Cervarix was awarded the first tender for school-aged girls, and in Q1 of this year, we grew Cervarix by 170%. SHINGRIX has already launched in the private pay market in more than 50 cities, and there's plenty of room to grow. With shingles, it's estimated to affect more than 1.5 million people aged over 50 in China every year. It continues to be recognized by the government as a priority disease. We are very pleased to see both Trelegy and BENLYSTA successfully achieve reimbursement coverage within the National Reimbursement Drug List for 2021. To put this in perspective, about 100 million people suffer from COPD in China, and currently, only around eight million are on maintenance medication. We are now making good progress in gaining market share in the single-inhaler market. With more than a million SLE patients, China is expected to be BENLYSTA's second largest market by 2025. If I now turn to our general medicines portfolio, this comprises all of our primary care assets, including Trelegy and ANORO. This business currently accounts for around 40% of New GSK sales, but we expect it to drop to around 25% by 2026 due to growth in vaccines and specialty medicines. With the majority of the LOE impact behind us by the end of 2021, we expect general medicines to provide a broadly stable and highly profitable base from which we can continue to fund investments in our priority therapy areas. Overall, whilst mature products will remain in decline, we see selected localized growth opportunities in the portfolio through a combination of targeted effort behind key brands and an optimized multi-channel approach to promotion. Trelegy is already a global growth driver, and we're competitively resourced to win by gaining share and growing the single-inhaler triple market in both asthma and COPD. We expect significant growth in emerging markets as well, where we are focusing on our investment behind key brands like Seretide and Augmentin, and we're working to make our infrastructure and capabilities more productive to drive general medicines. Strategically, these improvements should serve the business well when the time comes to launch new products in the region. Finally, to optimize the profitability and cash flow from general medicines, we're actively engaging and managing the portfolio by focusing on a smaller number of brands, improving COGS, and managing an efficient supply chain. Now, we've already reduced by more than 400 brands globally to around 200 since 2017 through divestment or partnering. This focus on portfolio simplifications, margin, and streamlining will continue. When we look beyond 2026, we have multiple opportunities to sustain growth despite the loss of exclusivity on dolutegravir in 2028, 2029. As you'll hear from Hal, the majority of our late-stage assets have the potential to be first or best in class. Combined with our growing commercial execution capabilities, we see the potential of the pipeline in these therapy areas to deliver peak sales in aggregate of more than GBP 20 billion on a non-risk-adjusted basis. Now, with the nature of our industry, it would be unrealistic to expect every agent in our pipeline to succeed, but the potential for growth is substantial, even before we add in contributions from the early-stage pipeline and future business development opportunities. Several pipeline products here have the potential to achieve more than GBP 1 billion, and some, like RSV and ASO, have non-risk-adjusted potential peak sales of more than GBP 2 billion. Now, they are almost all specialty and vaccines in nature, requiring smaller infrastructure than primary care. To conclude, we've made a large amount of changes in the commercial organization over the last three years with the objective of improving our capacity to compete and make the scientific case for our products. We've also sought to partner very closely with R&D to identify and develop vaccine and specialty assets in the pipeline that are compelling for doctors, payers, and patients. In doing this effectively, we had a stronger case to secure future growth. The aim of this presentation today was to provide you with the details on the action taken, and most importantly, the in-market evidence of the results of this progress. I'll now hand over to Hal, who will talk about the significant progress we've made in R&D. Thanks, Luke. I'm going to spend the next 15 minutes or so sharing an update on the progress we have made in R&D over the past few years and how the approach we set out in 2018 is delivering today for both patients and shareholders. I'll also highlight some of the key late-stage assets in our pipeline that we think have the potential to be transformational vaccines and medicines in the future. I'll mention a few of our most exciting early-stage assets and how these, coupled with further business development, will continue to contribute to our future growth. As you will see, our R&D approach has resulted in a significantly stronger pipeline with improved productivity. Our approach is based on five key pillars. First, we decided to focus on the science of the immune system, given its increasingly recognized importance in the pathophysiology of many diseases, beyond the classic autoimmune diseases. Second, by harnessing human genetics, functional genomics, and advanced technologies such as AI and ML, we can now identify numerous novel targets that have a higher probability of success. I will highlight an example of this when I discuss BLENREP in combination with a gamma secretase inhibitor for patients with multiple myeloma later. Third, we are strategically leveraging business development to augment our organic pipeline. Our recently announced deal with iTeos and this week's announcement by Deborah and the ViiV team on Halozyme highlights this. Fourth, we're working hard to improve our approach to developing our innovative vaccines and medicines following approval through more robust lifecycle innovation. Lastly, culture and talent are critical to our success, and we are making excellent progress towards improving senior leadership talent in R&D, reflected by the fact that 80% of vice presidents and above are either new to the role or new to GSK in the past three years. In addition, this approach is delivering operational benefits across vaccines and pharma with the recent creation of a Single Development Organization, which allows us to optimize the design and execution of clinical trials, as well as now having a single capital allocation process to ensure we're investing in the programs with the greatest benefit to patients and the most attractive returns. There are also important scientific synergies across pharma and vaccines, given the increasing convergence of prevention and treatment in the same diseases, and sometimes in the same patients. COVID-19 is a clear example of this with the development of both vaccines and therapeutics. We're also pursuing this approach in hepatitis B with our antisense oligonucleotide and our hepatitis B vaccine. Influenza is another good example. There are many other opportunities we're exploring. Our deep expertise in the science of the immune system and our focus on advanced technologies will continue to enhance our unique ability to deliver transformational medicines and vaccines for patients. These five pillars have had a significant impact on R&D, with 11 major new medicines and vaccines approved since 2017, which is top quartile performance. We also achieved a more than 90% success rate for pivotal studies and doubled the number of assets in phase III compared with 2017. The significant progress in R&D will continue our revenue growth with pipeline approvals since 2017, along with the anticipated approvals in the next four years, accounting for more than 100% of our forecasted growth from 2021 to 2026. With continued pipeline delivery and investments in business development, we're well positioned to support the longer-term growth ambitions highlighted by Emma. I'm very proud of this slide. It shows the 11 new medicines and vaccines R&D has obtained approval for in the last four years. The approval of JEMPERLI in April was our fifth in the last 12 months. In addition to that, we also received emergency use authorization for cetuximab. We also have had numerous approvals of our marketed medicines, which Luke highlighted earlier, including BENLYSTA for patients with lupus nephritis and NUCALA for patients with hypereosinophilic syndrome and patients with eosinophilic granulomatosis with polyangiitis. This is another very important slide, which highlights our R&D performance compared to our peers over the last four years based on data from Evaluate Pharma. As you can see, GSK is in the top quartile on key performance metrics from 2017 to 2020, including the number of launches achieved during this period, the number of launches per billion dollars of R&D spent, and the median peak year sales per launch. Compared to our peer group, we've delivered 40% more launches, nearly 50% more launches per billion dollars invested in R&D, and almost double the peak year sales forecast per launch. All of these improvements were driven by focusing on key assets, taking smart risks, and improving productivity, as I will highlight on the next slide. Simplifying governance has allowed us to significantly improve R&D productivity. It's enabled us to make better decisions faster and has contributed to an improved probability of success with more than 90% success rate from our pivotal studies since 2018. This is an improvement on the preceding three years, and as a reminder, the industry average success rate for pivotal studies is around 70%. In addition, we've reduced our cycle times by almost 20%, which is good progress versus our previous performance. Although we still need to do a little bit more to improve to be in the top quartile, we're on the right track. This progress, combined with our focus on lifecycle innovation, has enabled a significant transition in our pipeline. We now have double the number of assets in phase III studies compared to 2017. Improvements in cycle times have been driven by focus, operational excellence, and smart risk-taking. This slide highlights a number of these examples. The first is BLENREP, our anti-BCMA targeting agent for patients with multiple myeloma, which was approved just over two years after the start of its first pivotal study. The second is our RSV for older adults, where we implemented an accelerated development plan and have initiated a phase III study in order to be first in class. Third is our two COVID therapeutics. Our partnership with Vir was signed in April of 2020 for a late-stage research project. We received emergency use authorization from the FDA 13 months later. Similarly, for otilimab, we initiated our proof of concept study weeks after the start of the pandemic and delivered encouraging proof of concept data within eight months. This slide shows our R&D pipeline and our 62 potential vaccines and medicines in development. Over 70% of the pipeline now focuses on modulating the immune system, with an industry-leading infectious disease portfolio making up more than 50% of all assets and a growing oncology therapeutic area accounting for approximately 25% of the pipeline. As you can see, there are a number of assets here that form part of our response to COVID, including four vaccine programs, three of which leverage our proven adjuvant technology. Two of these will have pivotal data in the second half of 2021. We also have an mRNA COVID vaccine through our collaboration with CureVac on their second-generation technology, which I will cover in more detail later. We have two therapeutic programs, depemokimab, which recently CD-DOA, as I mentioned, and otilimab, where we will have additional data before year-end. We are very excited about our robust late-stage pipeline, with many assets having the potential to be first or best in class, as well as most of them offering significant strategic lifecycle opportunities. Deborah, Kim, Roger, Luke, and I will be spending much of the presentation today covering these assets in more detail. These programs all have significant potential on a non-risk-adjusted basis, and as you will see on the next slide, drive a substantial portion of our expected growth over the next five years. Specifically, the vaccines and medicines approved between 2017 and 2021 are expected to account for over 60% of the 2021 to 2026 sales stagger. The anticipated approvals of some of the late-stage projects I highlighted on the previous slide are expected to drive over 40% of the sales stagger over this time period. In addition, as well as having an exciting late-stage pipeline, we also now have a robust early-stage portfolio with a number of innovative programs that we believe have the potential to transform the lives of many patients and contribute to our growth ambition beyond that mentioned by Emma. In addition to this organic innovation, we will continue to strengthen our pipeline through business development, where we will remain focused on programs that are genetically validated and/or complement our commitment to the science of the immune system. We will begin to provide more details on these assets in due course. To that point, it is important to note the progress we have made on our commitment to leveraging business development to strengthen our pipeline. In the last three years, we have doubled the number of deals signed with long-term strategic intent underpinning these agreements and their synergistic impact on R&D. Our deals are already delivering significant value through the creation of a synthetic lethality pipeline and research unit, the acceleration and expansion of our immuno-oncology portfolio, the building of a state-of-the-art human genetics and functional genomics group, as well as AI and ML capabilities, and the access to key platform technologies such as mRNA, antibody-drug conjugates, antisense oligonucleotides, and T-cell therapies. Together, these deals have added new programs to the pipeline and helped to create a portfolio of exciting early-stage assets. Going forward, we will continue to augment our pipeline and capabilities through business development. In conclusion, our numerous approvals, significant business development, continued progress on key assets, and commitment to improving our R&D productivity has resulted in a significantly stronger pipeline. The momentum we are generating across R&D is helping to build a sustainable pipeline of innovative vaccines and medicines that will deliver for patients and for shareholders. I am very pleased with what the R&D organization has achieved over the past few years, and while there remains more to do, I am confident in our R&D approach and that it will continue to accelerate our progress and benefit many patients in the future. With that, I would like to invite Roger to join me to share our plans in vaccines. Thanks, Hal Barron. My name is Roger Connor. It's my privilege to lead GSK Vaccines. Today, Hal Barron and I will tell you all about this extraordinary business and show how we intend to strengthen our leadership and remain at the forefront of vaccines for years to come. There has never been a time where the importance of vaccines has been more visible to the world. As an integral part of New GSK, we intend to be the world's leading vaccines company over the coming decade and to deliver a high single-digit sales CAGR in the next five years. We've got scale. We're present in 160 markets with 25 marketed vaccines, supplying more than half a billion doses a year. We have world-class scientific capability, significant manufacturing expertise, and a know-how and a commercialization capability that we believe is second to none. There are three key takeaways we'd like you to remember from this session. First, we have the industry's leading pipeline with multiple potentially first and best-in-class assets and 16 assets in mid and late-stage development. We are planning five new launches by 2026, the most important of which is our vaccine for RSV in older adults. This is on track to be first and best in class, entering an estimated GBP 5 billion market. Second, our pipeline is underpinned by an unrivaled portfolio of technology platforms, including mRNA, that will ensure we continue to deliver highly innovative vaccines. Third, we will derive significant growth in the key categories where we compete. The biggest contributor will be SHINGRIX, our vaccine to prevent shingles, which we expect to double revenues over the next five years. We also aim to double revenues in the next 10 years in our market-leading meningitis franchise. We are today announcing a new strategy to strengthen our position in flu, the category in our current portfolio which mRNA technology has real potential to disrupt, by taking a lead in this disruption and advancing a portfolio of mRNA vaccine and antibody candidates with an ambition to double our flu revenues in the next 10 years. As a final point, you should note that our sales outlook in vaccines, and for GSK as a whole, does not include revenue potential from our COVID-19 solutions. Before I hand over to Hal, I wanted to show you the incredible portfolio of products we have in GSK Vaccines. We have the broadest portfolio in the industry, and as I mentioned, supplying 25 vaccines across 160 countries. Most importantly, the efficacy profile of our vaccines is excellent. 90% of our portfolio by sales has an efficacy level of above 90%. This is an incredibly high bar, protecting our portfolio from potential disruption from new technologies. One key question I am frequently asked is, "Is mRNA technology a risk for GSK, and will it disrupt your portfolio?" I am very confident the answer is no. mRNA is a massively exciting technology, and in fact, we see it as a major opportunity for the future, and this is why we're investing in it significantly. Hal will say more on this later. The risk to the current GSK portfolio from mRNA, however, is small. There are two reasons for this. First, mRNA technology will not work against all pathogens, for example, meningitis or DTP, and also because of the very high efficacy bar I mentioned before. Now, in disease areas such as flu, where the efficacy is substandard, there's a real opportunity for technology disruption, and GSK plans to be part of that. More on that later. Now, Hal, over to you. Thanks, Roger. It's great to see the progress you've made leading the Vaccines group, and I'm really looking forward to partnering more closely with you on our exciting pipeline in the future. That is, when you get out of quarantine. Good luck with that. To be able to optimally prevent or treat infectious diseases, we need better vaccines and better medicines, and increasingly, for them to be used together. As I mentioned earlier, we are well-positioned in this important area, given our R&D strategy of focusing on the science of the immune system. Our vaccines pipeline is the foundation of our world-class infectious disease portfolio, and several of our programs have the potential to be transformational. Starting with RSV. In people over 65, there is a substantial risk of developing RSV pneumonia, with around 180,000 hospitalizations and unfortunately 14,000 deaths each year in the United States alone. Our older adults vaccine is in phase III and has the potential to be first and best in class. We also have a phase III program ongoing for a maternal vaccine to prevent infection in newborns for up to six months. Roger will cover both of these in more detail shortly. We are also working to make the first pentavalent meningitis vaccine available. Meningococcus is a gram-negative bacterium which can cause invasive meningococcal disease. This is another area of significant medical need, with an estimated 1.2 million people a year being infected with a mortality rate of around 10%. Antimicrobial resistance, or AMR, is a significant public health problem of increasing concern, which contributes to approximately 700,000 deaths globally each year. We have two vaccines in the clinic targeting key resistant pathogens, as well as three candidates in late-stage research. Our specialty medicines pipeline, we're developing gepotidacin, a novel type 1 isomerase inhibitor for uncomplicated UTI and gonorrhea. We also have a phase I asset called FimH, which has a novel mechanism of action targeting uropathogenic E. coli that is not dependent on bacterial killing and therefore not prone to developing resistance. We believe the key to a successful vaccines portfolio is access to a wide range of platform technologies, allowing the best vaccine to be designed for each pathogen, be it a virus or bacteria. I want to highlight the importance of several of these technologies, starting with adjuvants. Adjuvants are an area of strength for GSK, particularly AS01, the adjuvant used in SHINGRIX. We're applying AS01 across a number of our pipeline assets, and adjuvants will continue to deliver significant competitive advantage for GSK as they induce a more robust immune response, allowing for increased efficacy. As Roger mentioned, with the success of vaccines for COVID, mRNA is clearly now an established modality for vaccine development. GSK is making good progress on this important technology, and I'll cover this in more detail in a moment. For prevention of bacterial diseases, glycoconjugation technology is one of the most effective technologies, and our proprietary platform is ideal for developing vaccines, for example, against meningococcus. Viral vector technology is also useful to induce cellular immunity, which is required in certain settings, such as with our hepatitis B vaccine. Finally, our expertise in monoclonal antibodies, our deep capabilities in human genetics and functional genomics, as well as our focus on the science of the immune system, will enable us to benefit from the scientific synergies that are increasingly evident across prevention and treatment. I want to take a few minutes to cover in more detail our approach to mRNA, including the collaboration with CureVac on their second-generation technology, which Roger and the team signed last summer and expanded earlier this year. The key to next-generation mRNA vaccines is having multivalent potential while managing reactogenicity. We are focused on two approaches to achieving this. The first is to optimize the five-prime and three-prime regions to enable more efficient translation, which is the focus of our CureVac collaboration. The second is to use modified bases. As you can see on the left-hand side of this slide, the five-prime/three-prime optimization results in a 10-fold higher immune response compared with the unoptimized approach. Of course, we need to confirm this in the clinic, but it is clearly very encouraging. It is also worth highlighting that these vaccines have the potential to be stable at two to eight degrees Celsius. We expect two mRNA vaccines from our CureVac collaboration to enter the clinic in the next 12 months. The first is a multivalent COVID booster, and the second will be for Influenza. We know that efficacy for a flu vaccine is driven by the number of different strains you can immunize against, and with lower doses of mRNA, we believe we can develop a multivalent best-in-class vaccines candidate. The GSK vaccines group has been moving quickly to ramp up our capabilities at our research center in Rockville, Maryland, as well as globally. Now we have more than 200 GSK scientists focused on mRNA and are making large-scale capital investments in a global mRNA manufacturing network. With the investments we are making in this area, we are well-positioned to play a leading role with mRNA in 2022. In summary, on this slide, you can see our industry-leading vaccines pipeline, the majority of which we expect to be either first or best in class. We have the potential to launch five new vaccines by 2026 and will continue to progress our early-stage pipeline with five proof-of-concept readouts anticipated by the end of 2023, and five first-time in human clinical starts planned this year. I'll now turn it over to Roger, who will go into more detail on how this will contribute to our future growth. Thanks, Hal. This slide shows the key assets that we expect to drive our high single-digit CAGR growth ambition to 2026. The most significant is SHINGRIX, supported by our meningitis franchise, primarily Bexsero. In the latter part of the timeframe, our pipeline kicks in when we launch our RSV older adults vaccine, our meningitis ABCWY vaccine, and we start to see the fruits of our new flu strategy. I'll come back to all of these. Starting with our crown jewel, SHINGRIX, which delivered nearly GBP 2 billion in turnover in 2020. Shingles is a painful condition that will affect one in three of us in our lifetime. SHINGRIX delivers outstanding overall efficacy of 97% with similar efficacy out to four years. We have data awaiting publication which shows the duration of protection extends to double this up to eight years. This incredible profile sets the bar so high, we feel good about any potential attempts by competitors to enter this market in the coming years. Prior to the pandemic, our performance had been constrained by supply. Demand was unprecedented, but thanks to the acceleration of our capacity expansion, we are now unconstrained and in a position to supply all the countries where we want to launch and where the value of the vaccine can be maintained. What's really important to note is that despite the success we've had to date, we're just getting started with SHINGRIX. In the U.S., there are still about 100 million adults aged 50 plus remaining unvaccinated. Beyond the U.S., we have major opportunities for geographic expansion. We expect to be in 35 markets within the next three years, including 16 by the end of this year. As Luke mentioned, there's a substantial growth opportunity in China, where we launched in 2020 and are initially focused on the private market in major cities. Longer term, we have significant lifecycle management opportunities, with plans to expand the indication to adults with autoimmune disease and to reformulate into a fully liquid presentation, which will put us even further out of reach for any potential rivals in development. Taken together, we are highly confident that SHINGRIX has the potential to double sales in the next five years compared with the 2020 base, protecting more than 100 million adults along the way. Another important contributor to growth will be our meningitis franchise, where we have the industry's leading portfolio of vaccines. We currently hold more than 50% share of the GBP 2 billion market. Looking ahead, we expect to build on our leadership position with the ambition to double revenues in the next decade through market expansion and new improved combination products. In the near term, we expect to drive growth from our flagship MenB product, Bexsero. In the U.S. in particular, we see a market expansion opportunity given that MenB is the most common serogroup affecting healthy infants, children, and adolescents, and that penetration is currently below 25%. Our medium to long-term plans center on new combinations. Both our MenB and our MenACWY vaccines are competitive vaccines. The next step is to combine them into one shot. We have two MenABCWY combination vaccines in the clinic. Our first is in phase III and will report pivotal data in the second half of 2022. If successful, this will be a first-in-class asset with potential launch in 2024. We're also in the clinic with a second-generation MenABCWY vaccine that we believe will deliver further differentiation by providing the broadest strain coverage for infants and adolescents. As the only vaccine to potentially address every major meningococcal strain worldwide, we believe this has the potential to further build our leadership. Next, I want to talk about the late-stage asset in our vaccines pipeline that I'm most excited about. RSV is a very common respiratory virus and one of the highest value remaining unmet need in infectious diseases. In older adults, the hospitalization burden associated with RSV infection is higher than that of influenza. Now, this is really important. The burden of disease created by influenza is seen by governments as a very high priority to address with improved vaccines. The burden of disease of RSV is comparable, with an even higher risk of severe outcomes in hospitalized patients. With one billion people aged 60+ in the world and 70 million in the U.S. alone exposed to RSV every year, there is a significant addressable population, making the scale of this opportunity very large. We estimate the market size for RSV older adults alone at GBP 5 billion annually. We have the most advanced RSV older adults vaccine candidate in development. As Hal mentioned, what is important is that this vaccine incorporates our proven adjuvant, AS01, the same platform used in SHINGRIX, a highly efficacious vaccine in a similarly aged adult population. Last year, we reported phase II data that showed neutralizing antibodies are boosted tenfold compared to baseline, that the vaccine induces a strong T-cell response similar to that seen in young adults. In older adults, this is of fundamental importance in fighting viral infections. The FDA has granted Fast Track designation to this program, and assuming we're successful in phase III, we have the opportunity to launch a first and best-in-class asset in 2024. It won't end with launch in older adults, as we're planning life cycle innovation to expand use to younger adult populations with underlying conditions that may put them at a high risk of RSV, as well as assessing combinations with other adult vaccines. This vaccine is a major commercial opportunity with multi-billion-pound SHINGRIX-like annual potential, and we intend to maximize it fully. The burden of RSV is also significant in infants. We believe the best way to protect them, that is likely to be most acceptable to new parents, is through maternal vaccination. This will create immunity from the first breath without the need for injection of the baby in the first days of life. The opportunity here is the annual birth cohort, which is four million each in the U.S. and the E.U. alone, and 114 million globally. Polyclonal-induced immunity by our maternal vaccine offers broader protection than a monoclonal approach, addressing the risk of escaped viral mutants. It also has the potential benefit of protecting the mother, which is good for her and potentially reduces the risk of transmission from mother to baby. This vaccine is in phase III, and with Fast Track from the FDA, could launch as early as 2024, assuming positive pivotal data. Now, this is a crowded, competitive space, so the opportunity for further innovation is important. We're developing an RSV and pertussis combination vaccine, which is expected to move to first time in human study in 2022. This will be the first combination vaccine designed specifically for pregnant women to protect newborns from two important diseases. Being able to give a single injection against two pathogens the baby most needs protection from will deliver a competitive advantage. I'm going to finish with flu, where today we are announcing a new strategy based on the new or the renewed opportunity in this space. The disease burden remains significant, with up to 650,000 deaths from flu-related disease each year. Governments around the world are increasing vaccination levels, and we believe this will be maintained post-COVID. Consequently, despite suboptimal current vaccines, the market is expected to grow by more than a third by 2026. Our strategy will be delivered in a stepwise approach, leveraging new technologies to supersede our current egg-based approach. First, we have a clinical collaboration with Medicago to develop a flu vaccine using their innovative plant-based technology combined with our pandemic adjuvant. Now, this combination has shown very strong immunogenicity in COVID, amongst the best across all vaccines, including mRNA. This vaccine will be targeted at the 65-plus population, and we believe will be an improvement on the egg-based approach. Our collaboration is currently at the clinical stage with phase III data readout expected in the second half of 2023, and we're in discussions regarding details of a commercialization agreement. Secondly, within the next 12 months, as Hal noted, we're starting a first time in human study using the CureVac second generation mRNA platform to pursue a multi-antigen seasonal flu vaccine, with expected better efficacy than the current standard of care. In addition, we plan to develop a universal flu vaccine using the same technology. Finally, through our partnership with Vir, we have exclusive rights to collaborate on VIR-2482, a monoclonal antibody designed as a universal prophylactic for influenza A, with the potential to overcome the limitations of current flu vaccines, leading to meaningfully higher levels of protection due to its broad strain coverage. Flu is the one part of our current portfolio that is at risk from emerging mRNA technology, and our new strategy aims to ensure that we are net beneficiaries from this disruption to the marketplace. As a consequence, we have a new ambition to double our flu sales in the next decade, and this will be upside to New GSK's 2031 sales ambition. In summary, we are extremely confident that vaccines will deliver a high single-digit sales CAGR in the next five years. Furthermore, we have all the necessary ingredients, underpinned by a powerful pipeline and long-term competitive capabilities to sustain attractive growth and leadership over the next decade. I want to leave you with one important fact, which is why I get out of bed every day to lead this fantastic business. Around 40% of the infants in the world receive a vaccine made by GSK every year. The public health impact we make is immense, and it is something all of us at GSK are very proud of. Thank you. I'll now hand you over to Deborah Waterhouse and Dr Kimberly Smith, who will lead the next session on our HIV business. Good afternoon. My name is Deborah Waterhouse. I'm the CEO of ViiV Healthcare. I'm delighted to be joined by our Head of R&D, Dr Kimberly Smith. In this section, we are going to walk you through our strategy for the HIV business. Our growth ambitions, the transition of our portfolio from oral-based regimens to long-acting injectables, and of course, our pipeline. Our strategy is to remain innovation leaders in HIV, achieve a mid-single-digit CAGR to 2026, and digest the loss of exclusivity of dolutegravir through the changing mix of our portfolio and the success of our pipeline. In 2019, we changed the approach to HIV treatment with the launch of our two-drug regimen, Dovato, with efficacy non-inferior to a dolutegravir-based three-drug regimen. We are now bringing to market the first long-acting injectables for the treatment, and shortly, for the prevention of HIV. We believe Dovato, Cabenuva, and cabotegravir for PrEP will each deliver significant benefits for people living with HIV and will make a multi-billion-pound sales contribution. As we move into the second half of the decade, we anticipate we will see a significant acceleration in the uptake of our long-acting regimens, with cabotegravir replacing dolutegravir as the foundational medicine in our portfolio. We are excited by our early-stage development pipeline, which we believe offers potential for revenue renewal from 2026 onwards. HIV remains a global health challenge with significant unmet needs and a global market of around GBP 23 billion in value. The WHO and UNAIDS estimate that 38 million people are currently living with HIV, with 1.7 million new infections per year. The burden remains greatest in sub-Saharan Africa, and it is a sobering fact that around 6,000 adolescent girls and young women are infected every week. In the U.S., there are around 38,000 new infections per year, and the epidemic continues to disproportionately impact people of color and predominantly men who have sex with men. In Europe, we have a similar picture, with around 22,000 new infections per year. Despite treatment advances, the epidemic remains pressing and relevant, and the market opportunity remains compelling for those who deliver new and meaningful innovation. Our HIV business is positioned for growth, and we expect to deliver mid-single-digit CAGR from 2021 to 2026. Through the first half of the decade, the launch of new medicines, represented in orange, aims to accelerate the growth outlook for ViiV, underpinned by the continued trajectory of the oral two-drug regimens, notably Dovato. During this period, we anticipate transitioning to the long-acting portfolio with cabotegravir, creating two new market segments in treatment and in prevention. As we end 2026, we estimate that cabotegravir-based regimens will equate to around 35% of the portfolio. Post 2026, we are excited about our early-stage pipeline of new and innovative long-acting medicines, which will have the potential to power revenue renewal, and Kim will cover this later. Dolutegravir-based regimens are now taken by more than 17 million people living with HIV. That represents one in two on treatment today. Dolutegravir is an integrase inhibitor, which since launch has become a proven gold standard in treatment with eight superiority studies versus competitors, setting an incredibly high bar in terms of barrier to resistance and tolerability. We believe that innovative regimens, whether oral or long-acting, need to contain an integrase inhibitor. In 2019, we launched Dovato, which is a best-in-class two-drug regimen with dolutegravir at the core. Dovato is a pivotal medicine for our business. It has consistently demonstrated efficacy non-inferior to a dolutegravir three-drug regimen and delivers significant benefits to people living with HIV. A person living with HIV will be on treatment for the remainder of their life. Why should patients be exposed to three drugs when two is all they need? Despite the ongoing challenges posed by the COVID pandemic, Dovato has continued to perform strongly, as the graph on the left of this slide demonstrates. As a result of our excellent commercial execution and strong investment behind Dovato, we are now driving strong growth in both the U.S. and Europe, and particularly in the switch market. We expect Dovato to deliver more than GBP 1 billion of revenue in 2022, with further potential beyond that. We see the opportunity for Dovato as being balanced globally with around 50% of the potential sales in the U.S. and the remainder split between Europe and the rest of the world. Dovato is patent protected until 2028 in the U.S. and 2029 in Europe. I'm now going to walk you through the shape of the HIV business through the decade and our ambition to retain our leadership position as innovators in HIV. In this section, we will outline the expected transition from oral therapy to long-acting regimens and why, despite the loss of exclusivity of dolutegravir at the end of the decade, we remain confident in the outlook for our HIV business. Between 2021 and 2026, our HIV business is expected to grow mid-single digit CAGR, driven by Dovato, Cabenuva, and CAB-PrEP. By 2026, we estimate long-acting regimens will be generating around GBP 2 billion of our sales, and then post-2026, we're working to launch a self-administered long-acting treatment and ultra-long-acting regimens for treatment and for prevention. By 2031, we estimate 90% of our business will be in long-acting regimens, delivering significant value to patients and enabling our HIV business to deliver attractive growth. I will now hand to Dr Kimberly Smith to take you through the transition to long-acting regimens and our pipeline. Thank you, Deborah. Long-acting regimens are the future of HIV treatment and the driver of growth through the next 10 years. We are, and expect to continue to be, the leaders in this space. Through the next few slides, I'll articulate the comprehensive patient insights and scientific rationale that underpin our confidence. On the left of the slide, you'll see that patients are telling us that they want long-acting medicines. In our pivotal trials, 9 of 10 preferred long-acting regimens over daily orals, and the reasons behind this are clear. There are significant challenges with daily therapy. The fear of HIV status disclosure, stress and anxiety about staying adherent, and the daily reminder of living with HIV, which is highly stigmatized. Simply put, long-acting gives people freedom from the burden of daily oral therapy. In January of this year, we were thrilled to receive the FDA approval of Cabenuva, the world's first long-acting injectable treatment for HIV. It is also approved in Europe under the brand name Vocabria and Rekambys, with dosing every two months. We anticipate approval of two-monthly dosing in the U.S. by the end of the year and launch in early 2022. This is the first and only approved long-acting regimen. It reduces dosing days from 365 to six. It is powered by an integrase inhibitor. It has non-inferior efficacy and comparable safety to daily oral three-drug regimens. Excitement from providers and patients since the launch has been palpable. We are investing confidently in execution to support the launch. We have created a separate U.S. sales force. We are creating a robust digital and online presence to reach every appropriate provider and person living with HIV who could benefit. We're also generating strong phase III/IV data, including a head-to-head study versus BIKTARVY, to ambitiously evolve our label further. We believe the significant interest in long-acting from prescribers and patients will lead the long-acting market segment to grow at a fast pace, reaching GBP 4 billion- GBP 5 billion by 2030. With at least five years headstart on the competition, robust and compelling data, and positive launches already underway, we're confident about the potential of Cabenuva to transform the HIV treatment paradigm. Let's switch to a strategic priority for our HIV business, the prevention space, commonly known as PrEP. There are currently circa 200,000 people on PrEP in the United States, which is a fraction of the population that could benefit. The U.S. market is strong and viable, approximately GBP 1.5 billion in value today. We expect this to more than double over the next decade to reach GBP 4 billion-GBP 5 billion. The U.S. market is going to grow further because there's significant motivation from prescribers and health systems to increase PrEP use among individuals vulnerable to HIV. The U.S. government continues to focus on the goal to end the HIV epidemic by 2030 with an ambitious target to reduce new infections by 75% by 2025. CAB is a new long-acting injectable for the prevention of HIV and offers the potential to transform the shape of the epidemic. It's the first long-acting injectable for PrEP and is dosed every two months. U.S. patient demand for long-acting injectable PrEP is high. Stigma around PrEP and the perceived hassle of daily dosing are currently the top drivers of discontinuation of PrEP. Prescribers express concern about their lack of ability to observe adherence with current PrEP options. Cabotegravir addresses these concerns, and the data behind cabotegravir is outstanding, as you can see on the right of this slide. Data from HPTN 084 study, which compared cabotegravir long-acting to oral daily Truvada for prevention of HIV acquisition in women. In the graph, you see the rising solid purple line that represents increasing new HIV cases on the Truvada arm, while the dotted red line across the bottom of the graph shows a much lower number of cases on the cab arm. HPTN 083, which studied men who have sex with men, had similar results. These pivotal studies demonstrated superior efficacy in men and women, three to nine times better than oral Truvada. Both studies were stopped early by the independent data monitoring board, and all participants were offered the opportunity to switch to cabotegravir. This is unprecedented in HIV prevention. Last month, we began a rolling submission with the FDA for cabotegravir for PrEP, which we expect to be completed next month, and we anticipate approval late this year or early next year and launch in early 2022. If approved, we believe cabotegravir will represent a new and persuasive option in the PrEP market, dosed every two months with efficacy that is superior to the current standard of care. Now let's move to our pipeline, the engine that will drive future growth. We're confident in our pipeline of innovative medicines that all offer the potential to partner with cabotegravir to form complete HIV regimens. Importantly, integrase inhibitors, the proven gold standard of HIV medicine, are at the core of our portfolio. CAB200 is our current formulation, and CAB400 is a new formulation that provides more dosing options for future regimens. There are two clear objectives. To provide the world's first self-administered long-acting regimen, and to provide an ultra-long-acting regimen with dosing intervals of at least three months. Each of the assets on this slide has the potential to partner with cabotegravir, and each offers new mechanisms of action, which attack the virus in unique and powerful ways. With multiple shots on goal, we're confident that as we have over the past decade, we can deliver continued innovation over the next 10 years and beyond to ensure that no person living with HIV is left behind. This week, we had an exciting announcement about an exclusive licensing agreement with the life sciences company Halozyme. Halozyme's recombinant human hyaluronidase, or PH20, is a unique product allowing increased volumes of medicines to be delivered subcutaneously. It offers the ability to reduce volume limitations for subcutaneous dosing, potentially increasing dosing intervals. This expands the opportunities for ultra-long regimens combining cabotegravir with the ViiV pipeline products for treatment and PrEP. The exclusive collaboration covers targets for integrase inhibitors, capsid inhibitors, NRTIs, and gp120 CD4- binding site broadly neutralizing antibodies or bnAbs. We are the leaders in long-acting therapy today, and we have a robust plan to continue to be the leaders in this space. Let's lay out our ambition for our future pipeline. Dolutegravir has been the anchor for our regimens over the past 10 years. Cabotegravir will be the anchor for the next stage and is the future of long-acting regimens. We see this future in three stages. In stage one, you have the world's first and only approved long-acting regimen, cabotegravir for treatment, and hopefully soon, long-acting cabotegravir for prevention. These are administered in the clinic, offering privacy, reduced stigma, and reduced anxiety. In stage two, our ambition is to deliver the first self-administered long-acting regimen for treatment, continuing to offer the option of long-acting to more patients with fewer clinic visits. With Halozyme, we have the potential to increase the dosing interval for cabotegravir for prevention from two months to every three to six months. In stage three, we have a pipeline of agents with new mechanisms of action to combine with cabotegravir, which we believe will have the potential to create ultra-long regimens. We now have the world's only long-acting injectable for treatment, which has been approved. We're continuing to build on that first-ever transformative option, which will allow us to continue to lead the industry towards a future of long-acting treatment and prevention to improve the quality of life for people living with HIV. Now back to you, Deborah. In summary, our ambition is to reshape the HIV treatment and prevention landscape, maintaining innovation leadership in the long-acting space. We expect to deliver mid-single-digit sales growth over the next five years. Our exciting long-acting pipeline provides the opportunity for revenue renewal post the dolutegravir loss of exclusivity. It offers people living with HIV freedom from daily oral medication and governments the ability to transform the shape of prevention efforts. With that, we invite you to enjoy a 10-minute break before Luke and Hal start the next session on other specialty assets. Thank you. [Break] Welcome back. I hope you're all suitably refreshed and ready for the second session. You've heard about the exciting growth drivers in vaccines and HIV. Let's now move to our other specialty medicines. As outlined by Emma, we expect specialty medicines to deliver a double-digit compound annual growth rate to 2026. In this session, we'll go into some depth on the products driving this forecast across our infectious diseases, oncology and immunology respiratory therapy areas, as well as an important reagent in our opportunity-driven area. Hal and I are going to highlight the 10 specific high-potential assets, which you can see marked on this slide with an orange box around them. The large and small molecules we'll be highlighting are almost all first or best in class. Each has the potential to deliver a compelling benefit to patients as well as significant commercial opportunity for shareholders. To reanchor you in terms of the scale of the opportunity with these projects, this is the slide that was shown earlier today. The numbers in the middle outline how our late-stage pipeline could deliver greater than GBP 20 billion in sales on a non-risk-adjusted basis, with a summary statement including the primary advantage of supporting the peak sales estimates on the right-hand side of the table. Assembling these and our existing in-line products in this bridge slide, you can see that the trajectory leads to a 2031 sales ambition of more than GBP 3 billion. Please note that this does not assume a significant contribution from the early pipeline, such as some of the oncology assets Hal will be describing or the novel long-acting HIV combos that Deborah discussed. Also, it does not include any contribution from future business development, although this will be an important element of our strategy. With that brief introduction, let's move and discuss the assets. I'm going to start discussing two innovative infectious diseases projects, namely gepotidacin and our HBV therapeutic 836. Gepotidacin is the first in a new class of antibiotics with the potential to play a major role in combating antibiotic resistance in patients with uncomplicated urinary tract infections or with gonorrhea. This is an attractive commercial opportunity, particularly in urinary tract infections. Uncomplicated UTIs are of the most common bacterial infections that women experience, with over 15 million cases per year in the U.S. alone. However, resistance is increasing and driving the need for new second-line reagents. 38% of patients will have some form of resistant infection, and one-third of all patients will fail their initial treatment, requiring a second-line agent. At the same time as the need for them is increasing, the second-line options are dwindling due to resistance and safety concerns. Fluoroquinolones are the most commonly used second-line agent, but IDSA guidelines in the U.S. say they should not be used empirically where resistance exceeds 10%, yet we know resistance in the U.S. today is already double that at 20%. The FDA has also issued a black box warning for fluoroquinolones and guidance not to prescribe them for uncomplicated UTIs if an alternate treatment option is available due to the risk of adverse events. Despite these issues, this class still has 25% share due to a lack of alternative to physicians. This is the opportunity for gepo. It's a novel mode of action, gives it an efficacy against resistant pathogens, making it the ideal treatment to replace quinolones as the preferred second-line treatment for women with UTIs where resistance is a concern. Gepo only needs to displace one-quarter of the current quinolone use to become a blockbuster, and we look forward to the intra-phase III results in 2022. Moving to H36, we're excited by the potential to deliver a first-in-class functional cure for chronic hepatitis B, where there's substantial unmet need. The high prevalence of hep B coupled with low diagnosis rates and suboptimal treatments means this disease continues to have a devastating impact, with an estimated 900,000 people dying annually from complications of liver disease due to hep B. Around a third of patients are in China, where you heard me talk earlier about the ongoing transformation and upscaling of our business there to one based on vaccines and specialty medicines. H36 is a unique asset designed to bind to the hep B RNA, resulting in its degradation, thereby halting generation of the surface antigen and ideally restoring the immune system's natural ability to eliminate infected liver cells and control the infection for the long term. This was clearly demonstrated in our phase II-A program, in which H36 resulted in a significant reduction in hep B surface antigen across all treatment groups after only four weeks of treatment. We anticipate more real-life data from our ongoing phase II-B program assessing H36 versus standard of care in 2022. If successful, this could be a paradigm-changing medicine. With that, let me now hand over to Hal. Thanks, Luke. I just want to add my excitement about gepotidacin and our HBV antisense oligonucleotide, which really have the potential to be quite transformational for patients. Now moving to oncology, where our portfolio has grown and advanced significantly since 2018 and benefited from a focus on the science of the immune system and human genetics, as well as on business development. We have evolved from having no approved medicines and eight assets in clinical development, the most advanced being in phase I, to today, where we have three approved medicines, all of which have considerable life cycle innovation opportunity, 13 assets in development, as well as numerous exciting preclinical targets beyond that. The portfolio advancement we have delivered has been driven by internal research efforts as well as through business development, resulting in exciting immuno-oncology, cell therapy, and synthetic lethality portfolios. Let me turn now to the asset in our pipeline which has seen the most significant acceleration since 2018. BLENREP, our first-in-class BCMA-targeted therapeutic, was our first oncology medicine to launch and was approved based on deep and durable responses seen in patients with advanced myeloma in the DREAMM-2 study. As I mentioned earlier, this is an example of rapid development, with the approval of BLENREP coming just over two years after the initiation of the study. Now, multiple myeloma is the second most common hematologic malignancy, with a global incidence of more than 170,000 patients per year, and sadly, it is almost always still a death sentence. Fortunately for patients, there are a number of therapeutic options available or in development, with the most prominent being those that target BCMA. BLENREP has a number of advantages beyond being first to market. As an ADC, it's an off-the-shelf product, which can be administered in a community setting and is immediately available to patients via simple 30-minute infusion every three weeks. Our extensive ongoing clinical trials program is designed to extend the use of BLENREP to earlier lines of treatment based on the compelling efficacy we've seen to date, including with the ALGONQUIN data shown on this slide, where a 95% response rate was achieved with a 2.5 mg per kg dose. The majority of patients do not develop symptomatic ocular events, and only around 3% of patients actually discontinue treatment due to these events. We're investigating ways to better manage these ocular events. As you can see on this slide, in the ALGONQUIN study, reducing the dose by just 25% led to a significant reduction in Grade 3/4 keratopathy. We're optimistic that further dose optimization work will reduce these events and enable more patients to get this important medicine. In addition, we have a number of ongoing combination studies, including one with a gamma-secretase inhibitor to further lower the dose, which I'll cover in more detail now. Now, I've mentioned this combination previously and remain very excited about the potential of this proof-of-concept study. This is a terrific example of how incredibly powerful functional genomics can be in identifying potential targets. The study on the left side of the slide by Kampmann et al. uses a CRISPR knockout screen to identify targets which increase BCMA cell surface expression. Basically, these types of studies evaluate the impact of knocking out a gene and seeing if it increases expression, the dots on the right, or decreases expression, dots on the left. This can be done on a whole genome scale routinely now through our collaborations with the LGR and the Broad. Amazingly, the top hit in the screen were the four subunits of gamma-secretase. This implies that of all the genes explored, inhibiting gamma-secretase is the most likely to provide synergistic activity. We complement these studies with biology, where we now understand the mechanism by which gamma-secretase inhibition prevents the shedding of the receptor. As you can see on the far right, there's marked improvement in the cytotoxicity assay when combined with BLENREP. Thus, we believe this will allow us to maintain the impressive efficacy at a lower dose of BLENREP, which should reduce the incidence of ocular events. Of course, we need to see if this translates into patients, and we have a substudy within DREAMM-5 exploring this combination ongoing, and we expect to have preliminary data by the end of this year. Next, I would like to highlight our most recently approved oncology medicine, JEMPERLI. While there are a number of PD-1s approved and in development, JEMPERLI provides GSK with several unique opportunities. First, we're very proud to have received approval for JEMPERLI as a second-line monotherapy treatment for women with dMMR endometrial cancer, given the significant unmet medical need. The second opportunity is in areas where PD-1s have not yet been licensed, including in the first-line treatment of women with endometrial cancer, where we will see data from the RUBY study in combination with chemotherapy in the second half of this year. We're also exploring combinations with JEMPERLI in ovarian cancer and in multiple myeloma. Lastly, the most significant opportunity is the potential for combinations with our novel immuno-oncology portfolio, though it is worth remembering that IO is a high-risk area, as reflected by recent readouts on ICOS and TGF-beta. We continue to believe that some novel combinations will be successful, and given the profound potential impact on patients, we think this represents a very smart risk. One of the most exciting opportunities in this space is through modulating the CD226 axis, and the next slide describes this in more detail. Based on robust preclinical data, human genetics, and recent randomized clinical trial data, modulating the CD226 axis looks to have very promising potential. Let me take a minute to explain why this is. TIGIT, CD96, and PVRIG are all expressed on different T and NK cell subsets, and each function as immune checkpoints by binding to CD155 and CD112, and thus preventing activation of the CD226 axis. Thus, antibodies to TIGIT, CD96, and PVRIG disrupt this binding to 155 and 112, allowing the immune system to recognize and kill the cancer cell. The preclinical data on the right side of the slide shows that by combining antibodies against PD-1, CD96, and TIGIT, synergistic benefit is achieved compared to either doublet alone. I hope you can see why we are in a very unique position now to fully unlock this axis, having acquired a PD-1 through our acquisition of Tesaro, advanced an anti-CD96 with 23andMe, in-licensed an anti-PVRIG from Surface Oncology, and most recently obtained an antibody to TIGIT from iTeos Therapeutics. If this translates in the clinic, we will be leaders in the new era of immuno-oncology, delivering transformational medicines to patients and value to shareholders. Moving to another exciting area of oncology. I highlighted the GSI example to just demonstrate the immense power of functional genomics. Our confidence in ZEJULA and the PRIMA study was another example of these unique insights. Based on functional genomics, we were confident that ZEJULA would benefit more women than just those with the BRCA mutation. Given the results of the PRIMA study, I now believe we have the best-in-class PARP inhibitor. Luke will speak to this in more detail in a moment. Through building world-class human genetics, functional genomics, and AI ML capabilities, we've expanded our synthetically valued pipeline beyond ZEJULA, now with the collaboration with IDEAYA. This has added a number of exciting targets to our portfolio, including the MAT2A inhibitor, which entered the clinical earlier this year. The finding that MAT2A inhibition is synthetically lethal in tumors with MTAP deletion is very exciting. As you can see on this slide, MTAP deletion is common in a number of solid tumors. We have two other promising pre-clinical targets with Ideaya, the Pol Theta and the Werner helicase. The emerging data from our own internal programs based on the functional genomics is identifying a number of other targets. I am very confident this will enable us to have a world-class synthetically valued pipeline. I'd like to now hand it over to Luke who will cover ZEJULA in more detail. Thanks, Hal. We covered the recent performance of ZEJULA earlier. This slide outlines the longer-term potential. The current pandemic has unfortunately seen a delay in the diagnosis and subsequent treatment of new cancers. However, we expect this to recover towards the end of 2021. In ovarian cancer, when we look at maintenance therapy, it remained underutilized with around 60% of women who could potentially be receiving it still on a watch-and-wait strategy despite the data. To address this gap, we continue to invest in education of both physicians and patients, and I'm very pleased to report patient awareness of the options for maintenance therapy is increasing, up from 29% in 2020 to 45% in early 2021. We see opportunity to further drive market growth as PARP inhibitors remain underutilized in first-line maintenance of ovarian cancer, particularly in the BRCA wild type and HR proficient patients, for which ZEJULA is the only PARP inhibitor indicated for first-line monotherapy maintenance. We also believe ZEJULA has the potential to improve outcomes beyond ovarian cancer. In terms of the lifecycle work with ZEJULA, we have four pivotal studies currently ongoing in lung, breast, endo, and ovarian, in addition to a large number of investigator-initiated experiments. Pleasingly, in November, we dosed our first patient in the exciting ZEAL 3 pivotal study. With a unique pharmacokinetic profile of penetrating the blood-brain barrier, there is the potential to impact disease with brain mets and CNS involvement, which could result in a best-in-class label in non-small cell lung cancer. Finally, we've recently started opening centers for our phase III registrational trial for ZEJULA in breast cancer called ZEST. The design includes two cohorts, BRCA mutant and BRCA wild type. Like ovarian, we expect there'll be biomarker populations beyond BRCA mutant that benefit from ZEJULA. This study employs circulating tumor DNA to identify tumor recurrence after adjuvant treatment before it progresses to radiologically detected metastatic disease. This is the first time that ctDNA is being employed in a pivotal breast cancer study identifying those patients that are most likely to progress. This is really important because physicians may be reluctant to initiate treatment in these women at this stage of the disease. However, confirmed presence of tumor DNA would be expected to shift this balance substantially in favor of neoadjuvant therapy. If we move now to immunology and respiratory, our long-acting interleukin-5, GSK3511294 or depemokimab, is our opportunity to expand our leadership in severe eosinophilic asthma, given the contributing and continuing high unmet need and economic burden. IL-5 antagonists and other biologics are effective drugs, but only 27% of eligible patients right now receive a biologic, and of those 50% remain uncontrolled despite being on therapy. This low adherence and treatment reluctance with injectables factors strongly in these numbers. Building upon the efficacy and safety of mepolizumab, GSK3511294 has been engineered for high affinity and longer-lasting suppression of IL-5, enabling continuous control. Our development program has also been designed to optimize eosinophil levels whilst offering patients more control and quality of life with a single injection delivered every six months. A robust real-world evidence program is also in place to cement the importance of patient preference linked to clinically meaningful outcomes. The attractive profile of 294 and the development plan informed by deep experience with the IL-5 mechanism could see 294 not only become the biologic of choice in severe EOS asthma but also expand large molecule usage in these patients. Back to you, Hal. Thanks, Luke. I just want to add my excitement about the development of depemokimab, which we progressed into phase III earlier this year, straight from phase I, just based on robust PK/PD data. Another important asset within our immunology therapy area is otilimab, which I mentioned earlier when I discussed our solutions for COVID. Otilimab is also in phase III development program for rheumatoid arthritis. Around 1% of the world's adult population suffers from RA, and despite many treatment options being available, around 40% of patients treated with a biologic still report daily pain. What we hear from clinicians is that patients need better treatment options to control their symptoms, especially pain. Otilimab is a novel monoclonal antibody targeting GM-CSF, and phase II data suggests that it may have a differentiated profile in terms of pain and disease control independent of inflammation control. Our phase III trial programs, called ContRAst, is on track to read out by the end of 2022 and will provide us with data versus JAK and IL-6 inhibitors. Now the final asset I'd like to cover today is daprodustat. Daprodustat has the potential to be a very transformative new medicine for patients with anemia associated with chronic kidney disease to improve upon standard of care by effectively, consistently, and safely managing hemoglobin with the convenience of oral delivery. We have a fully recruited, robust Phase III clinical development program, which employs active standard of care comparisons in both the dialysis and the non-dialysis population. It also utilizes a single hemoglobin target worldwide, and we believe these studies will provide adequate power to describe the cardiovascular safety profile without the requirement for a meta-analysis. We look forward to sharing the data from the ASCEND program soon. If positive, these data could have a significant impact on patients and represent significant value for GSK. In conclusion, I want to take a moment to highlight the strength of the pipeline we've covered today. I hope these assets, along with the approvals we've already delivered since 2017, our emerging early science, and our commitment to further business development, gives you the confidence in our ability to deliver on our future growth ambitions. With that, I'd like to hand it back to Luke. Thanks, Hal. This concludes our overview of the products with the greatest near and long-term potential across vaccines and specialty medicines. I hope you found it useful. We have an attractive and balanced portfolio focused on our key therapy areas, while enabling ourselves to be flexibly opportunistic where the science takes us. Key in the near term will be the strong execution and delivery of our development and commercial organizations. This underpins our growth expectation of more than 5% CAGR between now and 2026. Equally, we are clear that we can unlock the value of our current late-stage pipeline to deliver our ambition of more than GBP 33 billion in sales in 2031. On top of which, we would, of course, expect to add in growing contributions from our early pipeline and for future business development. Thank you. With that, I'll hand over to Iain. Thank you, Luke and Hal. As you've heard today, we're confident in delivery of sustainable growth and competitive shareholder returns. What we mean by this is captured on this slide. We expect to deliver a sales CAGR of more than 5% between 2021 and 2026, secured through pipeline productivity and commercial excellence. We expect to deliver an adjusted operating margin of over 30% by 2026, driven by significant shift in sales mix towards vaccines and specialty medicines and continued cost discipline across New GSK. With sales growth and continued cost discipline, we expect to deliver adjusted operating profit CAGR of more than 10% over the next five years. To be clear, these outlooks do not include any revenues or profits from COVID-19 solutions. From 2022, New GSK's cash generated from operations is expected to be further improved by operating leverage, cost productivity, and working capital improvements. In addition to strong operating cash flow performance, on separation of the Consumer Healthcare business, it will strengthen New GSK's balance sheet, giving us the financial flexibility needed for a growth-focused capital allocation strategy. We expect to have leverage of less than two times net debt to adjusted EBITDA at the point of separation. Regarding capital allocation, our disciplined approach is focused on strengthening the pipeline, ensuring long-term sustainability of all aspects of our operations, and delivering sustainable returns for shareholders. A progressive dividend policy is a central element of our capital allocation discipline, I'll cover this in detail shortly. As a leadership team, we're confident in our ability to deliver this growth. For the next 10 minutes or so, I'll provide the detail that informs our confidence. This slide sets out our ambition for sales growth over the coming decade and the key drivers of that growth. Through pipeline productivity and commercial excellence, as set out earlier by my colleagues, we expect to deliver top quartile sales growth over the next five years and aim to grow revenues to more than GBP 33 billion by 2031, more than offsetting the anticipated impact of loss of exclusivity of dolutegravir. From 2021 to 2026, we expect to deliver more than 5% sales CAGR, driven by both recently launched products and anticipated approvals from our late-stage pipeline. We expect sales of products behind major pipeline approvals between 2017 and 2021 to deliver over 60% of sales growth over the next five years. Each of the marketed assets noted here will play a significant part in delivering this growth. We expect anticipated approvals of transformative best-in-class assets like cabotegravir for PrEP and RSV for older adults, continued development of ZEJULA and BLENREP, as well as other assets from our late-stage pipeline to deliver the remaining 40% in top line growth to 2026. Looking further ahead to 2031, we've set an ambition of delivering more than GBP 33 billion in sales. This is driven by effective commercialization of in-market assets and anticipated progress in our late-stage pipeline, which you've heard about from Hal, Luke, Roger, Deborah, and Kim, and is before any significant sales contribution from earlier stage pipeline or any contribution from future business development opportunities. As a consequence, we're very confident in our ability to execute our 2031 sales ambition. Reflecting on our late-stage pipeline, we see a combined peak year sales potential of over GBP 20 billion on a non-risk adjusted basis. Not only is this well above non-risk adjusted consensus forecast, but it provides the opportunity to take a substantial beyond our risk-adjusted ambition of more than GBP 33 billion in sales by 2031. Our top-line ambition for the coming decade is robust. The very significant transformation realized in R&D productivity and commercial execution across our portfolio underpins our confidence in delivering these expected outcomes. We expect to expand our operating margin to at least 30% by 2026, with more than 10% adjusted operating profit CAGR over the next five years. The key drivers of this growth are higher sales of vaccines and specialty medicines delivering improving margins through operating leverage and mix, completion of major restructuring programs and disciplined cost control. There are no further major restructuring programs planned. Increased R&D productivity will allow us to continue to secure pipeline approvals while slowing the significantly increased rate of R&D investment seen in the last few years. Ongoing productivity initiatives across supply chain, commercial operations, and global functions reflecting our ambition of achieving and maintaining upper quartile peer benchmark comparators further contributes to improving operating margins. At the same time, to win in the market, we must invest. We will invest the right resources behind our pipeline, new launches, and commercial capabilities to ensure we sustain our potential for growth. We'll do this while maintaining a sharp focus on enhancing return on investment to constantly manage the impact on margin and operating profit. Finally, on this page, you'll note that we expect cessation of Gardasil royalties in 2023. An important driver of margin improvement over the next five years is a marked shift in portfolio product mix. The growth of vaccines and specialty sales relative to a broadly stable revenue and margin outlook for our general medicines portfolio contributes to operating margin improvement up to 2026. In addition to this very significant mix shift to vaccines and specialty, we'll continue to actively manage the general medicines portfolio for operating profit and cash generation. As Luke mentioned earlier, we have already delivered significant streamlining and simplification of the general medicines product range. This work has been achieved through a combination of reducing the complexity of the product range and divestment of certain brands where the economics are attractive. This work will continue. Close collaboration between our commercial and supply chain teams will continue to deliver network simplification and improvements in cost of goods sold. With our commercial team, we'll continue to sharpen our focus on growth markets and tailor go-to-market strategies. Across our businesses, we'll maintain a disciplined approach to cost management. You'll find in the appendix detailing how we intend to report each of our three product areas, as well as the overall reporting framework for New GSK. Over the last three years, we've made great progress in delivering improved cost productivity. We'll build on this progress and maintain a focus on further sharpening our resource allocation and cost discipline. We'll continue to see delivery of the results of major restructuring carried out over recent years, with these programs completing in 2022. In total, for these projects implemented between 2018 and 2022, we expect to deliver annual savings of GBP 1.5 billion by 2023. As noted earlier, no major restructuring programs are planned. From our Future Ready program announced in early 2020, we expect to deliver an additional GBP 200 million of savings for a new total of GBP 1 billion with no additional implementation costs. Of the total expected annual savings of GBP 1.5 billion, we expect to reinvest approximately one-third into the growth drivers of our business. Our focus on disciplined cost management is evident across all parts of the business. Examples of savings included in the GBP 1.5 billion total are in R&D, where synergies are being unlocked through implementation of our One Development Organization, which encompasses both vaccines and specialty medicines development, and supported by R&D productivity improvements as Hal shared earlier. This contributes to savings of around GBP 300 million. In our manufacturing network, following site and brand rationalization, plus efficiencies derived from the application of automation and AI across our global network, we'll deliver savings of around GBP 400 million. In our reshaped global support functions, we expect to deliver top-quartile efficiency and cost competitiveness, allowing New GSK to be leaner and more productive. This focus is a major contributor to the very significant savings in SG&A across categories, but it goes well beyond reshaping the capabilities of our global support functions. We continue to assess all categories of SG&A spend with a particularly sharp focus on non-customer facing activities. We've made very significant progress, and we know that new ways of working in the post-COVID environment, as well as agile resource allocation, which prioritizes return on investment, will support delivery of more savings in the future. You can see the progress we've made already. This is work we now do well. Our progress in every area gives us confidence that we can deliver the changes needed to make New GSK highly competitive and more financially efficient. Turning to cash generation and conversion, the expected revenue growth and margin expansion I've noted, combined with effective working capital management and the completion of restructuring programs, will strengthen cash generation and conversion. We expect cash generated from operations for New GSK to exceed GBP 10 billion by 2026, a significant step up from 2020 levels. Our teams are delivering top quartile performance in working capital management for days sales outstanding, days payables outstanding, and returns and rebates management. There is both a significant focus on and significant opportunity to deliver improved inventory management. This is a long-cycle opportunity, but our teams have actions in place to deliver significant improvement in days inventory outstanding over the next five years. Through the investment cycle and supported by recapitalization upon separation of Consumer Healthcare, we expect to continue to strengthen our balance sheet. From a credit ratings perspective, we're targeting short-term ratings of A1/P1 and commensurate long-term ratings. Our corporate treasury team continues to deliver improvements in our cash management processes and is very effective in deploying efficient, low-cost funding strategies in support of our capital allocation priorities. Our capital allocation priorities remain unchanged. Firstly, further strengthening of R&D pipeline, including through focused bolt-on acquisitions and in-licensing arrangements. Secondly, ensuring successful new product launches. Thirdly, delivering growing and sustainable shareholder returns. Our capital allocation framework is clear and simple. Firstly, we invest in the pipeline and R&D capabilities to continue to innovate, improve productivity, and deliver future growth. This includes business development, which will continue to play an important role in strengthening our pipeline, where we'll prioritize bolt-on acquisitions and strategic collaborations to strengthen the pipeline. To ensure we make the best use of our resources, we've set clear criteria for evaluating opportunities. These include alignment to our R&D strategy and our core therapeutic areas, sizable market opportunities with significant unmet need, and first-in-class or best-in-class potential, a balance between non-organic and organic investment, and NPV and IRR thresholds set to deliver improving returns. Secondly, we invest behind product launches and customer and patient-facing activities delivering commercial excellence. Thirdly, we intend to invest between GBP 1 billion and GBP 1.5 billion annually in capital projects focusing on efficiency and effectiveness of all aspects of our business and the long-term sustainability of New GSK. Last, but by no means least, shareholder dividends. Moving on to our dividend policy for New GSK. As Emma mentioned earlier, we will implement a progressive dividend policy guided by a 40%-60% payout ratio through the investment cycle. This is a key part of our capital allocation framework. We believe that setting dividend policy in this way ensures we deliver competitive, growing, and sustainable shareholder returns while supporting the investment needed to deliver growth. On this slide, we set out our expectations for dividends over the next two years. There's no change in the expected dividend for full year 2021 of GBP 0.80 per share. For 2022, for the first half of the year, we expect to declare a GBP 0.27 dividend for the current GSK group. GSK is on track to separate into two new companies early in the second half of 2022, and we expect the aggregate dividend across the two new businesses to be at GBP 0.28 per share for the second half of 2022. On a full year 2022 basis, this is equivalent to pro forma group dividend of GBP 0.55 per share, representing a 31% cut from GBP 0.80 per share dividend expected for 2021. This expected pro forma aggregate GBP 0.55 share dividend for the full year 2022 is comprised of GBP 0.44, representing New GSK's policy, and expected GBP 0.11 from the Consumer Healthcare business. Clearly, dividend policy for the new Consumer Healthcare company will be set by its board of directors. In 2023, the first full year of standalone operations for New GSK, we expect to declare a full-year dividend of GBP 0.45 per share. On this slide, I set out more detail on the Consumer Healthcare separation. We remain very much on track to separate in mid-2022, and over the last two years, Brian McNamara and the consumer team have done an incredible job integrating two large and complex businesses. Commercial integration activities are all but complete, and manufacturing activity is well underway. The team expect to deliver targeted integration synergies of GBP 500 million annual savings and are on track to deliver operating margins in the mid to high twenties. Brian and his team are establishing a unique and highly attractive growth-orientated Consumer Healthcare business. The GSK board has reviewed multiple alternative approaches to separation of Consumer Healthcare, always with a lens focused on unlocking potential in both new businesses, strengthening GSK's balance sheet, and maximizing shareholder value. We intend to merge at least 80% of GSK's holding in the joint venture to a new company with a premium London Stock Exchange listing. We believe this approach creates an attractive growth opportunity for our investors and is intended to be structured in a manner that is tax efficient for U.K. and U.S. shareholders as compared to alternative separation options. Importantly, a significant majority of our long-term investors have expressed a preference for this approach to separation. We intend to retain up to 20% in Consumer Healthcare as a short-term financial investment and expect to monetize this holding in a timely manner to fund our capital allocation priorities and help fund certain pension benefit obligations. Before separation, we'll build the capital structure of new Consumer Healthcare and expect to lever the company up to four times adjusted EBITDA. Shareholders of the consumer JV will receive a pre-split dividend, and we expect GSK share to be worth up to GBP 8 billion This represents a significant recapitalization of GSK’s balance sheet and is in addition to proceeds realized from monetization of the retained shares. We expect New GSK’s leverage will be less than two times net debt to adjusted EBITDA at separation, with the reduction primarily driven by pre-split dividend. Along with the strong cash generated from operations mentioned earlier, this will support our growth-focused capital allocation framework. Bringing together these financial factors, the outlook for New GSK is compelling. We see strong sales, profit growth, and shareholder returns over the coming decade. From 2021 to 2026, we expect sales CAGR of more than 5%, which, combined with disciplined cost management, is expected to deliver more than 10% adjusted operating profit CAGR and at least 30% operating profit margin by 2026. The resulting strong cash generated from operations will support our growth-focused capital allocation framework and a progressive dividend policy. We have a set of 2031 sales ambition of more than GBP 33 billion and have confidence for all the reasons you've heard today in our ability to deliver this ambition. With that, I'll hand back to Emma. Thank you, Iain. The last four years have seen transformative change across GSK, across multiple dimensions addressing long-term historic issues. We now have in place a clear platform to deliver a step change in performance and create value for shareholders. Value delivered by New GSK, a business revitalized around new vaccines and specialty medicines, and value delivered through separation to unlock the potential of a new world leader in Consumer Healthcare. New GSK will deliver a step change in performance. Over the next five years and beyond, we have the portfolio and pipeline to deliver meaningful new growth. We're confident we can deliver the targets we've set. More than 5% sales growth, more than 10% adjusted operating profit growth, more than GBP 33 billion of sales by 2031. This is a holistic performance model, sales, profit, cash flow, capital allocation, and dividends founded on a rigorous assessment of our plans and expected delivery. With our innovation, we can prevent and treat disease. Our purpose will be to unite science, talent, technology to do all of this, operating in a responsible and sustainable way. We are committed to delivering global-scale human health impact together with improved performance returns and value for our shareholders from a company where outstanding people thrive. We have the ambition, the momentum, and the team to get ahead of disease together. Thank you. Welcome back. I'm going to start with some questions that I can read on the screen. I'll read them out, then, of course, we'll go to the line. First of all, what factors did you consider when deciding the mechanism for consumer separation? Why have you decided to retain a stake, and why up to 20%? As a follow-up, when will you sell down the stake, and what are the tax implications? I'll ask Iain in just a second to pick up on some more of the details, but just to remind you what we stated earlier, the board obviously put an enormous amount of thought into the different options that we had around the mechanism for separation, and there were three really clear criteria. First of all, to unlock the value of two businesses. Secondly, to strengthen the balance sheet of New GSK, which we do, of course, through the improvements in our operating cash flow, but through the separation, both through the up to GBP 8 billion dividend and the short-term retention. Thirdly, and in absolute primacy, is shareholder value creation. On that basis, that's why we decided to go for demerger and retention of the specific stake. We know it was one of the questions that shareholders wanted us to answer today to be clear exactly about the mechanism. As Iain stated in his presentation, this was a stated preference for many of our long-term shareholders. Iain, perhaps you could give a bit more details on the other supplementary points. Yeah, absolutely. As it relates to 20% retention, that's of our stake. You'll recall that our stake in the joint venture with Pfizer is 68%. 20% of that, broadly speaking, somewhere around 12%, 13% would be the maximum amount that we would expect to retain. The expectation is that will be a short-term financial investment. It'll be sold down on a timely basis after the separation. Once new Consumer Healthcare has a listing, premium listing in London Stock Exchange, with almost certainly ADRs listed in the U.S. also. We'd expect to sell that down on a timely basis. In terms of tax implications, this is structured in a way that's intended to be efficient for our U.S. and U.K. shareholders. When we de-merge, and those shareholders would receive a share in the new Consumer Healthcare business, that should be, and this clearly is subject to approval from both HMRC and IRS, that should be a tax-free event up to the point that then those shareholders might choose to monetize that stake, which would then obviously trigger tax. This should be an efficient approach for certainly a significant number of our shareholders. Thanks, Iain. Next question. You refer to pharma and vaccine synergies frequently, but apart from COVID, I'm not clear on where these exist. Do you have tangible examples? Iain, I'm going to come to you in just a second on the way we approach capital allocation and the financial synergies, and then probably over to you, Hal, on R&D and science. Let me first of all say that both vaccines and specialty medicines are absolutely core to the strategy of New GSK and, as we've seen today, to the growth of New GSK. Our purpose is to get ahead of disease. That means being about both prevention and treatment. Our R&D specialties are all around the science of the immune system, which is obviously relevant both across vaccines, but also across all four of our core TAs. In terms of operating synergies, I'll just point out that our Chief Commercial Officer here runs all of the general managers, with the exception of our ViiV business that obviously Deborah Waterhouse leads. A general manager in every country is accountable for both our vaccines and our specialty and general medicines business. In fact, right at this moment, I think we have some [Scholl's] sales reps who are supporting in the U.S. our drive for SHINGRIX uptake post the success of the COVID vaccination program. Actually, Iain Mackay, you also referred to in the cost review that how through the Future Ready program, we've been sort of de-duplicating, if I can say that, where we don't need to have separate structures, but in our corporate and back offices, there are a lot of synergies there that we've been increasing as we come together through the catalyst of the separation. Iain, perhaps you could talk about the really critical capital allocation point for us. Certainly, Emma, the operational efficiencies that you talked to go to the one development organization that Hal's leading the development of with Roger, and it goes into our corporate functions, our supply chains as well at a certain level. When you come back to capital allocation aspect, allocating our capital, which is focused on the development and strengthening of our pipeline, it gives us a breadth of opportunities in terms of putting the capital where the greatest opportunity is for GSK across our therapeutic areas through vaccines and our specialty businesses. I think Hal's put a really strong discipline around that. I think, Hal, you can probably go into a lot more detail about what this really means from a capital allocation perspective across the portfolio. Thanks, Iain. There are so many different ways that the vaccines and pharma groups can come together for synergies. The capital allocation, just to add a little more color on that. At the PIB, when we're faced with these interesting decisions about which assets to back, how much capital to put behind them, we have very robust efficiency frontiers that allow us to evaluate within pharma which assets are more attractive from a how many patients we can help, what's the commercial value. We use the probability of success and the revenue curves generated by Luke. By having the opportunity to allocate capital across both pharma and vaccines allows us to move money to where the great projects are. I'm sure we'll optimize the portfolio just by having that incremental opportunity. It's an important one. The one development organization clearly is going to add synergies. When you think about the convergence really that's occurring in pharma and vaccines in terms of, we used to think of diseases either needing prevention or needing treatment. They're really converging. COVID's a great example, but we have others. Particularly when vaccines like in flu aren't working at the above 90%, which we would love to have, there's an opportunity to use a vaccine in conjunction with an antibody. That's what we're doing with the Vir antibody and the flu vaccine, potentially a multivalent with the mRNA. Lots of interesting ways to think about that. Hepatitis B, another great example, because another sort of opportunity in vaccinology is to develop what's called therapeutic vaccines. We can actually use it in patients with the disease to treat them. Therapeutic vaccines are often very attractive, and when you think about the fact that we have, and Luke talked about this, the HBV antisense oligonucleotide for hepatitis B, now you're seeing that we have two different approaches in the same disease. The synergy's there in terms of a development plan, unique endpoints, operational efficiency, for sure. There's an enormous amount of synergy on the science side that I just take a minute to talk about. We can think about our focus on immunology is essentially vaccinology. It's a focus on the immune system. Our deep focus on immunology on the pharma side really complements what we're learning in the vaccine side. An example of this, when you think about it, our focus on immuno-oncology, what is that doing? It's waking up the immune system to allow our endogenous immune system to see foreign antigens called cancer cells. That's what an adjuvant is for vaccinology. We're actually contemplating maybe some of the reagents we're developing in immuno-oncology like STING, a STING agonist, might be a very effective adjuvant. Okay, we're learning from vaccine trials which of the polyclonal responses, which monoclonal might be driving that vaccine response. Well, that monoclonal, if we figure it out, could be a therapeutic. Learning from trials, learning pre-clinically the bioassays that we're developing to get a sense of whether the vaccine's working. There's so many different things I could talk about, there's enormous amount of scientific synergy as well. Very exciting. Fantastic. Okay, next question. What led you to set the dividend at this new level? It seems generous given the focus we heard about today on investing in the pipeline. Well, absolutely right. To reiterate, as shared by both myself and Iain in our capital allocation priorities, that our number one priority continues to be to invest in our future growth in the pipeline, both organically and inorganically. That is clearly our priority, and we are really pleased to be able to use this separation as a catalyst to keep strengthening the balance sheet so that we can invest in that growth. At the same time with this new policy, provide competitive and progressive returns. I'm going to ask Iain again, sitting right next to me, so you get all the questions. Yes. I'm going to ask you to give a little bit more specificity on how we and the board came to this policy, and how we thought about it. Yeah, absolutely, Emma. There's a very strong focus on the investment and strength of the pipeline, but also setting a dividend at a level that is both sustainable, but importantly progressive. The opportunity to grow this dividend as earnings improve over the coming years is a really important aspect of this policy. I wouldn't say 40 or 60 is a target. It's a corridor within which we would expect to operate, and that certainly will allow us to grow the dividend over the coming years as earnings improve, but also to sustain it in the longer term. When you'd naturally expect in some years, we'll see EPS variability. I think this strikes a very appropriate balance between setting an attractive return, which by the way, we think compares very well with a peer group in the industry, and allows us to strike this right balance between investing in R&D and long-term growth, improving the overall flexibility and strength of the balance sheet over time, and setting an attractive policy of returns for shareholders with the potential to progress it and grow it over time. Yeah, exactly. Again, this was, we know, a key question for investors, so we wanted to be very specific, very clear on it today, right down to the penny. Hopefully, that's helpful for everybody. Okay, now I think, hopefully this works, we're going to go to the phone line. Thanks very much. You have a question on the line. It comes from the line of Graham Parry from Bank of America. You are live on the call. Please go ahead. Graham. Thanks for taking my questions and thanks for the meeting and presentations today. Firstly, for Roger on SHINGRIX. Talking about doubling sales in five years is actually broadly what the Street is expecting at the moment. Does that take you to capacity, will growth then become capacity constrained beyond that, and perhaps flatline relative to expectations? Secondly, for Iain, on the gearing less than two times net debt to EBITDA post-split, how are you treating the ViiV put and the pension liabilities within that? You're treating those as debt, and what leverage would you be happy to stretch that back up to for the right deal or deals? Thirdly, on HIV for Deborah or Kimberly, on the IP protection on the Halozyme cabotegravir products. Do you expect these to have longer dated protection than the cabotegravir 2031? Is there any possibility to pilot technology to any other novel molecules coming through the pipe, or are we just really pushing the dolutegravir cliff from 2029 to a cabotegravir cliff in 2031 in the HIV franchise? Thank you. Fantastic, Graham. Thank you. Let's take those in order. Roger? Graham, thanks very much for the question. A simple answer is that we will not be capacity constrained going forward. We will not have a ceiling. We've done incredible work on the whole manufacturing side to accelerate that capacity expansion on a number of different fronts. The supply will not be a constraint for us. What I would say on SHINGRIX, obviously, it's a massive brand for us. It's a huge opportunity. It's going to contribute to growth for a long period of time. At some stage in the U.S., we will maximize in terms of the catch-up cohort. Luke also then shared the geographic expansion plans, which again, are significant. 35 additional countries in terms of the number that will be launched in the next three years. Geographic expansion and further indication expansion for SHINGRIX will be a key driver for us going forward. Supply is something that we should not be concerned about. Yeah, Graham, great question. Thank you. On leverage, we expect less than two times net debt to EBITDA. Our contingent liabilities as it relates to Shionogi and the like are not an integral part of that calculation. In terms of what we think the overall strengthening of our balance sheet means, where I think you're going from a business development perspective is the focus, whether it comes from the stronger cash flows with clearly some guidance set in that regard today, coming from obviously growing sales, improving operating profits, expanding margins, the deleverage of the balance sheet on the back of the dividend from the pre-split, before the split of Consumer & Healthcare, all help strengthen the balance sheet and form a much lower leverage point, and then obviously inform the strategic flexibility and the strength of that balance sheet to continue to do business development along the lines that we've done. We're very focused on bolt-on acquisitions, in-licensing agreements. Those worked very well for us over the last couple of years. Clearly, as we strengthen the balance sheet, it increases our capacity and capability to continue to pursue the strengthening of the pipeline as we've done over the last few years. Very happy with where that takes us and the opportunity to move forward from here. Just to remind everybody, when we say more than GBP 33 billion, that does not include any contribution from any further business development or very little from the early pipeline. Of course, we expect all of that to continue to accelerate considering the recent momentum. One of our most recent deals, of course, with Halozyme. Deborah, I don't know how you and Kimberly. I'll start and hand over to Kim. Just on the question that Graham asked. Where we are today is we have cabotegravir for prevention, which hopefully will be approved by the end of this year and launch next year. We have rilpivirine, brand name Cabenuva, which was launched at the beginning of this year, and offers long-acting opportunities for people living with HIV. Obviously, we're playing in the prevention space in the near future. That's great news. The Halozyme deal, which Kim will talk about in a minute, gives us more shots on goal. It gives us the opportunity to really aim for an ultra-long-acting prevention and treatment opportunity for people living with HIV. It really does give us an opportunity to bring extra time in terms of ultra-long-acting to our pipeline of medications. We don't get any additional IP, Graham, from the Halozyme deal itself. What we do get is from the medicines we can add to cabotegravir, we basically have a sort of second generation of long-acting medications, and the medicines that you put with cabotegravir have patent life into the 2030s. That is where you see the portfolio moving beyond the 2020s into the 2030s, and that is how you generate long-term value from having cabotegravir at the core. In the last 10 years, we've had dolutegravir, which we built a franchise around with Tivicay, Triumeq, then moving into Juluca and Dovato. Now what we're going to do is exactly the same over the next 10-15 years and beyond, where we have cabotegravir at the core, Cabenuva today, and CAB PrEP now, just about to come, and then you add these additional medicines, new mechanisms of action onto cabotegravir, and that takes you into the next decade and past the 2031 patent date for cabotegravir alone. That's kind of the way I'd see the IP landscape. Kim, maybe you'd like to say a few words about the Halozyme deal. Right. The Halozyme deal is extremely exciting because of the possibility of what it can do for each of the products. The one that's right in front is obviously cabotegravir, where we already have cabotegravir out to every two months. The combination with Halozyme potentially could get it out to every three months and beyond. That is the same thing for every one of the other mechanisms of action that I mentioned in the pipeline for our future combinations with cabotegravir. Each one of those mechanisms of action was already selected because of its potential as a long-acting agent. What the Halozyme deal does is takes it to being an ultra-long-acting. Instead of thinking of it as can it be a month, can it be two months, we get to starting to be confident that we can get at least one, if not several of those products to three months or more. What it really does is increase our shots on goal to get to that ultra-long-acting combination. That is really what patients are telling us. The longer the better, and that's what we're intending to deliver. Thanks, Kim. I've got to say, it's been fantastic to see the way that you've led the pioneering innovation in our HIV business. First with dolutegravir, first with two-drug regimens, first with long-acting, completely pioneering data in terms of the CAB PrEP, it's going to be exciting to see what we do with the longer-acting. Fantastic. All right, next question, please. Very much. Your next question on the line comes from the line of Seamus Fernandez from Guggenheim Securities. You are live on the call, please go ahead. Seamus, we can't hear you. Perhaps we can come back to Seamus and go to the next caller on the line. Yep. The next caller on the line is Laura Sutcliffe from UBS. You are live on the call, please go ahead. Hello, thank you. Thanks for the detailed update today. First question is on core operating margin progression. If it's achieved largely via shifting product mix, should we assume that sort of the bulk of that improvement is back weighted towards the end of the 2021-2026 time period. Second question is just on BD and strategy. I think you talk about your BD strategy being directed towards bolt-ons and in-licensing. Does that signal more of a desire to own your opportunities outright rather than partnering or further JVs? Lastly, on the mRNA vaccines program, can you sort of do multi-antigen mRNA vaccines and make the economics work, cost of goods wise? In other words, what conditions would need to be met for them to be viable commercially? Thanks. Okay. Well, let's go to Iain first on the progression of core operating margin. Although I think you'll get guidance in here. Then I'd like Hal to talk about our overall approach to BD, because we've had a huge acceleration recently, but also looking forward, and again, it's not included in our outlook any future BD yet. Then actually, we'll come to Roger on mRNA, including that factoring into COGS, please, in that order. Laura, margins. Mix is a clearly important component of this, but so is the continued focus around cost management, productivity, and efficiency. As we set out today, we've delivered already GBP 500 million of savings from programs that we've executed between 2018 and now. We'll deliver another GBP 1 billion of savings between now and the end of 2023, with most of those programs completed in 2022. Then there's an ongoing focus on what we do in terms of productivity and efficiency day-to-day. We expect to see improving margins coming through from 2022, and we'll continue to build from there. We've set out an operating profit CAGR of more than 10%, an operating margin of more than 30% by 2026. We're going to start moving in that direction from 2022. It's just continuous progression. I'm not going to give you a totally linear set out year by year, but clearly, when we get to setting our annual guidance, we'll clearly set out our expectations in each year. Hal? Yeah. Thanks, Laura, for the question. I think just to back up, our focus in business development, which we think is a very important way of augmenting our organic pipeline, is to really focus on the strategy we laid out in the middle of 2018, which is to look for opportunities that leverage our focus on the science of the immune system, as well as opportunities that leverage our understanding and focus on human genetics, functional genomics, machine learning. To be more specific, we look for opportunities that in immunology, if we can see some unique opportunities that would fit strategically with what we have. With the focus on the immune system in immuno-oncology, as you've seen, we've done deals that have bolstered our focus on the CD226 axis. For instance, we did a deal with iTeos recently for the TIGIT antibody. We had done, prior to that, a deal with Surface Oncology on the PVRIG. We had advanced a CD96 into the clinic with 23andMe, the first of that collaboration to get into the clinic. Of course, with the Tesaro acquisition, the PD-1. That's a good example of how we're using our focus on the science of the immune system, our focus on oncology as a therapeutic area, to then craft a number of business development deals to result in this, what we think, a very impressive CD226 strategy. We also have opportunities with human genetics to pursue everything from novel genetic targets that we have insights to from, say, 23andMe databases or Open Targets or FinnGen or the U.K. Biobank that we think are unique knowledge we have that others don't. That's another area that we're going to focus on. Also, of course, human genetics, functional genomics allow us to do a lot of interesting business development with companies that might be having synthetic lethal targets. For instance, the opportunity that we had to do a deal with IDEAYA, where we now have in the clinic a first in class MAT2A inhibitor in phase I, which as I mentioned earlier, is going to be potentially very synergistic in patients whose tumors have the MTAP deleted. We also have got the Pol Theta and the Werner helicase as well. You can see how our business development strategy is really complementing our research focus as well as our TA focus. In terms of types of deals, of course, we're open to bolt-ons, we're open to product deals, and of course, you mentioned would collaborations be an option, and of course they are. We're open to a lot of different things. I think one of the things, Hal, that you've brought a lot for us is the gated risk in some of these partnerships and collaborations, which I think has made quite a big difference in terms of our capacity management. We'll continue to pursue all of that. Roger, over to you on mRNA multivalent and COGS. Thanks very much for the question. On mRNA, we're incredibly excited by the technology. There's a major opportunity for GSK here, and it's one that we're investing in significantly as well, and adding it to our portfolio of technologies that we have. Specifically on multivalent mRNA vaccines, I think that is going to be an area of opportunity for us as well. On our second generation CureVac partnership, that's one thing that attracted us to that technology is the potential for lower dose, and that lower dose allows you to add more antigens potentially and avoid increased reactogenicity because of that lower dose as well. You'll see us doing this in both our COVID multivalent approach and our flu strategy that we talked about today, bringing a multi-antigen flu vaccine to the marketplace to ensure that it creates a differentiated, broader coverage also. When you've got that opportunity from this second-generation technology, we also think that we'll get combinations with potentially other disease areas, we'd be looking at flu combination with COVID. We could also be looking at combinations with RSV as well. Those are all things that we want to do and utilize this opportunity at a lower dose. Cost of goods I'm not worried about. I think obviously it's high at the start of a technology's life cycle, but particularly because the dose is smaller, as I mentioned, that's again, an opportunity for us. The other benefit of mRNA is the capital flexibility. You start to create multipurpose factories and reduce your capital bill as a result as well. I just think we'll see that cost of goods come down over time. If you've got a differentiated product, I believe the market will pay for that as well, and we believe we'll have differentiation, particularly in flu. Thanks. Roger, the next question, please. Thank you very much. Your next question comes from the line of Seamus Fernandez from Guggenheim Securities. You are live on the call. Please go ahead. Seamus, welcome back. I'm afraid we still can't hear you. Let's go to the next caller. We'll try again. No problem at all. Your next question comes from the line of Keyur Parekh from Goldman Sachs. You are live on the call. Please go ahead. Good evening, thank you for taking my questions. Please do, if I may. One, Hal Barron, Luke Miels, and Iain Mackay, you guys have given us a lot of details today. I'm just wondering if I look at that 2031 target you have set out for greater than GBP 33 billion in revenues, how much of that comes from the pipeline? I know you've given us details to 2026, but just wondering if you're able to give that to us towards 2031 as well. Secondly, on the mRNA vaccines. Roger Connor, I was wondering how confident are you feeling about both the CureVac partnership, given the data we've seen for the first-generation vaccine, and then secondly, on any alternative kind of optionalities you might have in-house. If you could just reiterate and give us reasons for why you think the naked mRNA technology from CureVac may not be a problem here. Thank you. Thank you. Okay, Iain, perhaps you could frame overall the contributions, then we'll ask Hal. I think it'd be very interesting for people to understand the sort of methodology we have around our forecasting and our asset build there, remembering it's all late stage contributing at this moment. Keyur, thanks for the question. I go back to the waterfall. Reflect on 2022 to 2021 to 2026 rather, very much driven by in-market assets and a contribution from late stage pipeline. You move to 2027 to 2031, very much driven by the late stage pipeline. Very little, if anything, well, very little contributed by early stage pipeline and nothing from BD that's not already completed. At a high level, those are the key contributors. As you move into 2027 to 2031, clearly the late stage pipeline continues, well, plays a more important role in terms of how we grow revenues through the latter part of the decade. I think getting into just some of how we inform, how we put that outlook of more than GBP 33 billion by 2031 together, Hal, in terms of how we think about risk adjustment within the portfolio overall as we see assets move through the clinic. It might be helpful if you provide a little bit of color in that regard. Sure, I can. We do it in a pretty straightforward and I think systematic and rigorous way. Basically, each asset we treat uniquely because each asset in the pipeline has a different probability of success based on a number of factors. First of all, obviously the most important being the phase. phase I assets typically have about a 10% chance of working. Phase II assets typically have about a 25%, and phase III, typically 65%-70%. Of course, any given asset will be above or below that, depending on the data generated, the preclinical data, the robustness of the target product profile, et cetera. For example, when we're looking at certain things like the daprodustat, where we have pretty compelling phase II data, and we are pretty confident it's raising hemoglobin levels from that. We might have a higher than average probability of success when in phase III. There might be opportunities like bintrafusp or ICOS that are in a therapeutic area, immunology, which is higher risk. They're in phase II, of course, where the probability of success is typically about 25%, and IO would be lower. We would put a much lower probability of success on that. Again, each asset is treated individually, and we then aggregate all those probability-adjusted numbers with revenues, as I mentioned earlier, generated by Luke and the commercial teams. And we use that for a lot of different things, but that's how we get to the risk-adjusted number that results in the 2031 revenue that you heard. Thank you. Let's come to Roger on the CureVac asset and how you may or may not want to add to Roger's comment. Thanks very much for the question. On the CureVac data that we shared last week, that is a technology that we're not actually involved in as GSK in terms of that development. We're very comfortable, though, with the second generation technology that we've done our deal based on. The way to think of this is it's an enhanced technology, a technology, as I just mentioned, that gives us this opportunity with lower dose for multivalent combination. Why are we so comfortable? I think when Hal shared the data, you saw some of the preclinical information, times 10 in terms of immune response versus first technology. Faster response after the first dose as well. Obviously, we've got to prove this in the clinic. We've got work to do. That is a major part of our mRNA play. There is optionality here. We want to make sure that we're looking at modified bases as well. Longer term, we have our in-house self-amplifying messenger RNA. I think about it as a longer-term option in terms of mRNA. Where we're putting our absolute focus at the minute is in that second generation technology and bringing it to the clinic efficiently and fast as well. We want to bring two assets through to the clinic in the next 12 months, and we want to put six assets through in the next four years as well. mRNA is a big part, I think, of vaccine development going forward, and we intend to be at the forefront of it, so we're investing significantly. Hal, would you add anything to that? Well, let me just emphasize a couple of things here. I think the key thing to remember is, at least our view, is that the future for mRNA vaccines are going to be multivalent. Multivalency requires a lower dose because you can't give a certain amount of mRNA without creating reactogenicity. If you're going to use multivalent vaccines, you got to get the number of micrograms per valence down. What CureVac's second generation, I think, is telling us is that when you optimize the untranslated regions on each side, the five prime, three prime, you get more efficient translation, more protein produced. That, combined with, and importantly, I think long-term, combined with the modification of the uridines to reduce reactogenicity because the total dose of mRNA with multivalency might start going back up for each valence, if you will. You really can imagine a next generation, if you will, of mRNA, where we can safely and highly effectively give multivalent vaccines with this combination of optimization of five-prime, three-prime, as well as the uridine modification. Thank you, Hal. Next question, please. Thank you very much. Your next question on the line comes from the line of Tim Anderson from Wolfe Research. You are live on the call. Please go ahead. Thank you. A couple of questions. Timeline for bringing an mRNA flu vaccine to market. One big pharma company with perhaps the deepest experience in mRNA at this point, made a comment to us recently. They thought it could be as short as two to three years. I'd be curious to get your opinion. On HIV, you guys talk about the value of two-drug regimens and the value of long-acting regimens. What worries me here is the competition in the form of Merck and Gilead, because they'll have not only two-drug regimens, but theirs will be oral. The crux of your long-acting approach is injectable, the cabotegravir, which I think is even intramuscular and not subQ. If their phase III trials go as planned, they'll have a once weekly pill for treatment and a once monthly pill for PrEP. I know you'll say they lack an integrase, but studies are underway to possibly show you don't need an integrase, and you could get rid of some of the weight gain that integrase would cause. How is this not a reasonable threat to GSK from mid-2020s onward? Thanks very much. We'll come to Deborah and Kim in a second. First of all, Roger, do you want to make any comments on timelines for flu? Yeah, certainly. I think I won't comment on what others have said in terms of their timeline. What I can tell you is the focus that we have at GSK on this flu asset in terms of our mRNA second generation play. I mentioned and Hal explained the need for a multivalent approach. That's exactly what we're expecting to do in this vaccine. We don't want to just come in and meet the current standard of care. We want to beat that standard of care as well, and we think we have an opportunity with that platform. Our timeline, as we mentioned in the presentation, we want to get into the clinic in the next 12 months. I think we'd want to get phase III data second half, probably of 2025 would be our realistic timeline in getting there. I think this will be the start of it, though. I mentioned combinations. The opportunity to add flu to COVID could be something we're looking at as well. I do believe that with the backbone that we have, there's a real opportunity for a universal flu play with this mRNA platform as well. Those are probably the key headlines. Thanks. Deborah. Thanks for the question, Tim. Over the last kind of eight or nine years, we've really established dolutegravir as the gold standard integrase inhibitor. Eight superiority studies versus competitors and one in two people treated across the globe taking a dolutegravir-based regimen at the moment. I think we've built an incredibly powerful franchise based around integrase inhibitors, which have an incredibly high barrier to resistance. That's the class that others will have to beat. Now we're moving into cabotegravir, and the era of cabotegravir, again, an integrase inhibitor at the heart of our future franchise. We talked today about how we are refocused on that proven technology with Cabenuva for treatment and cabotegravir for PrEP as sort of the starting point of our franchise. Over time, using the Halozyme design technology and adding that to cabotegravir, both in prevention and treatment, and then adding that to our other pipeline medicines, just gives an incredible opportunity for people living with HIV to have ultra-long-acting treatments or treatments that they're able to administer at home. We think that we've got a very powerful value proposition. Not to mention, obviously, at the moment, we have Cabenuva on the market, so a five-year head start versus our competitors in the treatment space and in PrEP. If we are successful in securing FDA approval at the end of the year, we'll have at least a three-year head start on our competitors in the prevention space as well. We're feeling very confident about our ability to compete. Kim, do you want to- You said a lot, but let me just add, I think, to emphasize why is an integrase important here? As you've already said, it's established, but it's established because it has a high barrier to resistance. It has durability in its efficacy. It has durability in its safety and tolerability profile. There's a reason why every guideline around the world is basically an integrase inhibitor is preferred. That is an established place that we are building on. I think that's a really important point. In comparison, our competitors are looking to establish new regimens with new mechanisms of action without that foundation. That foundation is particularly important, we believe. Then let me get to the other question around oral versus injectable. The idea that an oral is preferred over an injectable, I think is really subject to some debate. When you ask patients, they basically tell you that 70% of them would like a long-acting regimen. What they tell you is that the longer, the better. What is being, again, proposed by our competitors is a once-a-week oral option, again, combining two novel mechanisms of actions that haven't been proven to work well together and haven't been proven to have the capability to hold up as a two-drug regimen. Once-a-week still has some of the challenges that we described long-acting as actually responding to. This issue of being reminded of living with HIV, how frequently you need to take the medications. That is not improved by going from once a day to once a week. This issue of privacy and the potential of disclosure if you still have pills at home. It doesn't address a lot of those issues. There may be some patients who are interested in an oral once weekly, there's no question. Those are more likely patients who don't want to have an injection, because if you put the choice of can you be dosed once a week versus being dosed every two months or every three months or beyond, patients tell us over and over, the longer the better. We're not the least bit intimidated by the idea of oral versus injectable. We know patients want to be able to sort of decrease the impact of HIV treatment on their lives, and that means minimizing the frequency of dosing. That's what we're trying to do with our ultra-long-acting options. Thank you, Kim. We have now questions in on the screen from Seamus. Thank you. One quick one for Iain to clarify the definition of peak sales guidance, which is standard across the portfolio. Is that sustained annual and potential sustained annual peak sales or peak sales of a particular year? Then two for Hal. Firstly, when do you expect that we'll have data sufficient to know if your approach to HBV will result in potential functional cure, similar to what we've seen in HCV? Then secondly, what is your conviction based on for TIGIT, and what triggered the iTeos deal, ASCO data, and what's the view of differentiation of our assets and competitive positioning versus other TIGITs? Hal, quite a lot a few in that, Iain, perhaps. This is where we have Dr. Seamus Fernandez in the line, because I've got to be honest, I'm not sure I entirely understand his question. In terms of, if you like, what I would call an industry definition of peak year sales, it's the year in which you achieve peak year sales. If I go back to the outlooks that we talked to, that Roger Connor talked to, is the growth rate that we would expect to see come from our vaccines portfolio over the coming five years, where we see high single-digit CAGR over the period from now through to 2026. I've got a sneaky feeling, Seamus Fernandez, that might not entirely answer your question. If you go to a sort of classic industry definition of peak year sales, to the extent we've referred to that in vaccines, then I'd apply the same definition. I'd keep taking us back to the growth rate that we've set out, that we expect to achieve for vaccines over the coming five years, which is high single-digit percentage growth. Yeah. On the non-risk-adjusted 20, that's obviously aggregated peak single year sales, not achieved in a year. Anyway, Hal, over to you. Two questions, one on HBV and one on your excitement about TIGIT. Yes. Two good questions, Seamus. Thank you. I understand both. For HBV, couple things to remember. The antisense oligonucleotide study is really intended to do a few things. First of all, we had a very small number of patients in the phase II-A, so we're hoping to confirm that treatment effect was real. We're hoping to determine what incremental efficacy we gain by increasing the duration. As Luke highlighted, it was a relatively short course in the II-A. We're extending out that. We're looking at different ideas about whether you need to go for three months or six months, things like that. Probably most importantly in terms of the timing is that we really do believe after suppression, you need to see how long it takes for the HBV surface antigen to reappear, and that requires a 48-week endpoint. Upon conclusion of the randomization, you have another 48 weeks of follow-up to get that endpoint. We'll get a lot of data from that. What we won't know at the end of that, at least in theory, is whether that is the correct duration. Do we need less? Do we need more? Also importantly, because the whole hypothesis is that the elevated hepatitis B surface antigen might be inducing a type of immune suppression or a T-cell fatigue concept, and therefore, the next question that we'll have for this is, does this need to be combined with an interferon, for instance? There's a lot of people in the literature that suggest that that might be a viable way, since it does seem to be somewhat active in hepatitis B. There's also some really pretty interesting preclinical data on the utility of suppressing the hepatitis B surface antigen with a PD-1. These are questions that will have to be answered following that data. The short answer, just to get back to that, is that we should have data in the second half of next year, because the trials are rolling very well, we should actually finish it probably ahead of schedule, but it will require a 48-week follow-up. That's when it's going to take to see that data. A very exciting program. One, I think Luke mentioned there's 250 million people, and the morbidity associated with this is just terrible. I've seen many of these patients in the hospital. Not only do they have cirrhosis and all the complications, but in addition, hepatocellular carcinoma is not uncommon. Really can make a big difference for patients if this works. Very exciting. TIGIT, why do we get so excited about TIGIT? There's a number of reasons. Let me go into a few. First of all, like all opportunities, we first look at the preclinical data. It's pretty compelling, particularly when you think about the opportunity to add the doublet of a TIGIT and a PD-1, like dostarlimab, JEMPERLI. We were also tantalized. It's not an enormous amount of data, but very tantalized by the study I showed you where the triplet looks like that might be even synergistic. We have biologic rationale for that. That preclinical data made us very excited about the whole axis. That's actually not only did we in license, as you point out, TIGIT, but also that whole axis. CD96 with 23andMe and PVRIG with Surface Oncology. We have that entire pathway to clamp down on, which oftentimes will be incremental efficacy. The other piece that is really to us very important too is it's interesting that you can use human genetics sometimes to identify pathways or targets that you're particularly excited about. Again, using this proprietary data set with 23andMe, we did genetically validate the CD226 axis, so that gave us incremental confidence. To be honest, very important was the randomized phase II designed anti-TIGIT for Roche, where the treatment effect was very robust. Those three things together give us confidence they're all triangulating on that the likelihood that this pathway is active. The specific asset for ITS we liked because of a number of things. It was one of the more advanced ones relative to other opportunities. We do think that the Fc portion has to be enabled. There has to be a competent Fc portion. We believe there's debate out there, and we'll be getting data from Fc enabled and Fc super enhanced and Fc inactivated, and that will clarify that. We do think Fc activation is important. We see that preclinically with this ITS antibody. We also see it clinically where the T reg cells are profoundly reduced, which is actually unique compared to other anti-TIGIT. That's a particularly attractive aspect. It was only one patient, we did see monotherapy, which was unique for this monoclonal antibody. When you put all that together and the cultural fit with iTeos and the desire to be aggressive and the unique opportunity for this triplet, we were very excited about it. Luke, I don't know if you want to add anything to that. Yeah, just say how it also gives us strategic flexibility. We can get insights into CD96 or 96 combos. We have flexibility in terms of pricing. There's a lot of elements here. If you think about a triplet in future, the cost of that, if you put that into a co-formulation, it becomes very compelling for payers and patients alike. Thank you. Next question, please. Thank you very much. Your next question on the line comes from Kerry Holford from Berenberg. You are live in the call. Please go ahead. Thank you very much. Firstly, a question for Hal, just following up on the CD226 strategy. Clearly you have a number of bases covered here with a number of drugs at your disposal. I guess one of the key data readouts that we should look forward to, and when can investors better assess whether your focus on that pathway has been a successful strategy or not? Just give us some ideas on timelines looking forward here. In terms of divestment, I wonder if you could talk about your appetite, the opportunity to monetize perhaps some of the New GSK non-core products in future. Are there any brands or portfolios that perhaps reside within General Medicines that could be candidates for divestment going forward? Lastly, just going back to Graham's question on the leverage ratio in New GSK. It's clear that the pensions and contingent liability are not in your calculation, but what is the definition the rating agencies consider, and how might that influence your future BD strategy if you wish to maintain your A1 rating? Thanks so much, Kerry. I'm going to ask this so that we can keep getting through everybody's questions. Luke, perhaps you could comment a bit on the General Medicines portfolio. Sure. You've done a lot of work to clean that up. We'll come quickly to Hal on sort of data timings around the CD226 pathway. Let's start with you, Iain. Start with me? Yes. Okay. Excellent. Very good. Kerry, thanks for your question. Look, one of the things that we set out today was the target from a ratings perspective. Focused short-term ratings A1, P1 to commensurate long-term ratings. As you can imagine, we stay in very close contact with our rating agencies, S&P and Moody's. When we think about leverage, and clearly this is an incredibly important aspect of the financial strategy, is that we maintain strong ratings, improve the overall strength and flexibility of the balance sheet, ensure that we've got the capacity to continue to invest in R&D and the growth of the company. In terms of how we think about net debt to EBITDA, we always think about it in the context of how the rating agencies think about it, because that is going to define how we access the capital markets over the longer term. That conversation, which is an ongoing exercise with rating agencies, plays an important part of how we think about leverage for the company. I don't really want to go into the detail of how a rating agency is calculated, but we're very closely aligned in terms of how we think about leverage. Luke, over to you on General Medicines. I think in the general medicines portfolio, there's a lot of synergies in its largely primary care. We are very disciplined in terms of looking at this portfolio and turning it over. I mentioned earlier that we've dropped from 400 down to 200. If you look at markets, we've shrunk from, say, 140 down to 70. We're very disciplined in terms of whether that asset, whether that collection of products is best in our hands. We've communicated in the past in areas like derms. I think right now things are a little bit flat because of COVID, but in the future, you can imagine we'll be quite active there. We're looking around GBP 1 billion. Also in terms of monetizing some of these equity stakes in some deals as well. Thank you. Hal? Yeah, thanks, Kerry. It's a good question. We can't give specific timelines on a lot of things, but let me sort of outline how to think about how we're approaching the ungating concept. First of all, I think there's anti-CD96 is in the clinic for us. We're uniquely positioned by being first in class. If this pathway is important, this should be active. We're not necessarily as monotherapy, which is the current design, but once we get dose escalation and PD data and safety, we'll be moving to combinations with a PD-1 inhibitor with JEMPERLI. That could provide us with data if we start seeing activity. Like a lot of bio things, the timing depends on how much data you see. I think the second thing is for our TIGIT antibody, which we're in phase I with. We will be informed not only by our own data, but I think importantly by competitor data, both, as I mentioned, whether or not this FC competency issue is going to end up differentiating, and possibly importantly, whether the phase II data from Roche is actually confirmed in a phase III trial. It's also important to remember a concept that I think sometimes gets lost. There's first to approval, but there's also first in disease. I want to really highlight that we have a really robust set of studies that we're anticipating doing where we think while we might not be first to market in lung where Roche's and Merck are probably both ahead. We have some particularly interesting insights about other diseases that we might want to pursue, and we can use some data from external sources to ungate those trials. We're pretty confident with that. We're doing a lot of biomarker work, which I think can help us find kind of like PD-L1 and MSI to some extent were used for the PD-1 inhibitor class to optimize their development. We're also looking at whether various biomarkers I won't get into could be useful for optimizing our focus on the pathway. Finally, PVRIG, which will be in the clinic later. We think that that could also be an opportunity to play around with these combinations, not just triplets, but doublets with that. You can imagine all the different combinations. It's going to be complicated, but we're really excited because we think this very well could be TIGIT plus a PD-1 could be IO version 2.0 and may be analogous to what we saw with PD-1, pembrolizumab, et al, in that evolution. If the triplet should work, whether it be CD96, TIGIT, and JEMPERLI or even PVRIG in any combination, if the triplet should work, we think that's sort of IO version 3.0, which we think if that's to materialize, we would clearly be leaders. Very exciting next year or two with data unraveling, but very exciting pathway. I think this could be the future of IO. Wonderful. Thank you. Hal, next question, please. Thank you very much. Your next question on the line comes from the line of Mark Purcell from Morgan Stanley. You are live on the call. Please go ahead. Yeah, thank you very much, and thanks for all the work put into the Capital Markets Day today. First question on life beyond cabotegravir. You've previously talked to CAB400 being at the cornerstone with every one to potentially every three months subcutaneous dosing. In terms of gaining confidence in this strategy, when should we expect the first proof of concept data with CAB400? The first of the two combination partners that you mentioned today, the long-acting maturation inhibitor and the broadly neutralizing antibody. Just a point of clarification, will the ultra-long-acting options be self-administered with the PH20, or will they be physician-administered? Second, in terms of vaccine manufacturing capacity, could you also help us understand where you are in terms of building capacity behind RSV for older adults and RSV for the maternal side of things, where you'll be at launch and the timelines to expanding that capacity? Given Roger's comments in terms of unconstrained supply now on SHINGRIX, could you remind us of the size of the ex-U.S. target opportunity SHINGRIX in terms of patient numbers? I think in the U.S. it's 150 million people. The last one for Hal. In terms of probability of clinical and commercial success, if you take the sort of 11 key assets you've outlined with over GBP 20 billion worth of non-risk-adjusted sales potential, where would you consider the aggregate risk-adjustment probability today for those assets? Taking a specific one in BLENREP, what are the gating factors getting above GBP 3 billion in peak sales in terms of confidence? I guess there's obviously pivotal data, but also you mentioned the gamma secretase proof of concept data, and it's a very competitive landscape. How are you thinking about competitors in the ADCs as well as bispecific space? Thank you very much. There's a lot of questions in that, Mark. We'll go to Roger first, but just before that, on the question to Hal. We're obviously not going to put a specific number on the risk adjustment to that late-stage pipeline. I think Hal has outlined quite clearly how we look at the assets individually, but I will come to you, Hal, to pick up on the specific gamma secretase questions. First, let's go to Roger, then Kim. Three questions in there for you on HIV, and then we'll finish with Hal. Roger? Thanks very much for the question. On RSV, we are allocating capital and actually building capacity for RSV now. Just so you understand the antigen for RSV maternal and for older adult is the same, so that's great. It's one supply chain. For both. The good news is that it's also building off our CHO-based platform, which SHINGRIX is supplied on. All of the expansion that we've done on SHINGRIX and all of the improvement that we've done on SHINGRIX yield, which is unconstrained, as is being applied to RSV as well. From our perspective, we've allocated capital. We're going to be ready for this launch, and as I said during the presentation, we are absolutely going to maximize it. On SHINGRIX outside the rest of the world, we're being thoughtful in terms of where we go to. We want to make sure that we protect the value of the vaccine as well. Our markets are focusing on the private areas. I don't think it's appropriate to take all over 50s and apply that to the market globally, but there is significant opportunity. Luke particularly mentioned this in China, where we know in that private market we can achieve the same prices we're seeing in the U.S. as well. Lots of opportunity for SHINGRIX going forward, but RSV capacity, I would not be concerned about. Yeah, just one clarification. It's 115 million people in the U.S. above 50, around 67 million of those get a regular adult vaccination. Now can we stretch beyond that? I think Roger's point also, we have different strata in the markets, of course. In Europe, pricing is very much aligned with the U.S. as it is in China. As we get deeper into the life cycle, the question is, can we go for UNBs in emerging markets and fully extract the potential that this product has? Thanks, Luke. Hal, briefly. Yeah. BLENREP, I think you can think of as having sort of three end gaining events, if you will. The first will be efficacy as it relates to how it compares to active compared trials like in DREAMM-7 and 8 as well as DREAMM-3. We have ongoing phase III opportunities to move more proximally in the disease. That's from an efficacy perspective. We're also a whole series of studies looking at dose optimization, both seeing if we can reduce the dose, the duration, playing with a lot of different things to reduce the safety concerns with the ocular toxicity I mentioned. Third, where I think is very exciting is based on this functional genomics data and some pretty compelling biology, whether gamma secretase could be synergistic by allowing us to lower the dose to reduce ocular toxicity while maintaining the significant efficacy in that data. We should actually hopefully, it's a stretch goal for us to have that by the end of the year, but I'm cautiously optimistic we'll have that data, and that could be also very engaging. Three different ways to think about how to unlock value there. Great. Okay. There were a lot of questions there, let me quickly try to answer around CAB400. CAB400 is a reformulation of CAB200, makes it more concentrated, gives us the opportunity to give a bigger dose with a smaller volume. It really unlocks the potential for self-administration more than we had with CAB200. What we have now with the Halozyme deal is actually even more opportunity to give bigger doses subcutaneously. CAB400, CAB200, whatever formulation of CAB we're using is basically the foundation of how we build the self-administered regimens as well as the ultra long-acting regimens. Around the timing of when will we see some data on CAB400, we did have a little bit of delay related to COVID, so that will be around mid-year next year is when we will have those cohorts delivering that data. The second question was around the bNAb, so 109, which is N6LS. That proof of concept study is open and now enrolling, and so we expect to share proof of concept data for that in the first half of next year. The last question was around the Halozyme and the ultra long-acting and whether or not they will be clinic administered or self-administered. Really, when we get to these ultra long-acting timeframes, we actually think that probably is going to be clinic administered because that's around the timing that you would be bringing a patient into the clinic anyway, every three months, every four months, every six months. If we can do it in the clinic, then again, that gives more convenience to the patient, gives that privacy piece so that they don't have to worry about having products at home that have the potential for disclosure. That's about as quick as I can go. Thank you so much. We have one more. Yeah, of course. It's fantastic that we're going to have the CAB400 data towards the middle of next year, not just CAB400 on its own, but CAB400 as well with Halozyme. We've actually fast-tracked that as a proof piece of data. It's a key point. Thank you. We are going to extend the Q&A session. We want to get to as many of your questions as possible. We will try and answer them as succinctly as possible, but it will help if we don't get seven questions in one. With that point made, can we go to the next question, please? Your next question on the line comes from James Gordon from JP Morgan. You are live on the call. Please go ahead. Hi, James. Hello. Hi, James Gordon, JP Morgan. Thanks for taking the questions. One about HIV outlook and also one about vaccines. On HIV, I saw the projections for going to third injectable by 2026. What about further conversion beyond 2026 or 2027 once you've got oral that are generic? I ask particularly in Europe and ex-U.S. Do you see that Europe's going to keep on funding the transition to injectables once there are generic orals? I think a few years back there was comment that it sounds much more like it's a U.S. opportunity. Do you think you're going to get a similar tier of access led to the orals, or is Europe going to get tough once there's good old generic options? For vaccines, for RSV, the older adults is clearly a really big opportunity because you've got that big bonus of the catch-up potential. In terms of maternal and pediatric vaccines for RSV, where there's not a catch-up, it's just a birth opportunity, as I understand it. If there's about eight million annual Western births and you price it at GBP 150 a dose, my math says you need about 100% of pregnancies in the West and GSK to take 100% market share to get into even the bottom end of the range. Is that range assuming very big ex-U.S., ex-E.U. uptake, or have I done the math a bit wrong? Final one, just on SHINGRIX. Doubling to 2026, and I hear you're not capacity constrained post 2026. I think you've probably exhausted a good chunk of the U.S. catch-up bolus. What about the U.S. steady state once you've exhausted the bolus and you're just doing that U.S. birth cohort for SHINGRIX in the U.S.? Are we a long way off that already, or are we getting near that? Okay. Roger, do you want to cover briefly the two ends of the vaccines point? Luke, if you want to add to that, please do, and then we'll come to Deborah. Listen, thanks very much for the question. On the RSV maternal, we actually do see an opportunity here. As I mentioned, there is a real chance to make sure that we build off the current marketplace that exists for maternal vaccination, which is established within GSK, where we could build off the DTP and flu vaccines that are already given. We do think, again, that what's not fully understood is that this is a polyclonal approach and gives a potential differentiation versus a monoclonal approach going forward as well. We do think that this could be a very impactful vaccine, not only in the U.S. and E.U. that we mentioned as well, but then globally. RSV is something that we see occurring across the world. We do think there is an opportunity here. You're right, it's not as big an opportunity as the RSV older adult space. There is more competition in maternal as well. However, this is where I would point to the combination that we talked about today. RSV being combined with pertussis, we think could be, again, a game-changing opportunity. It's early. It's going to be going into the clinic next year. We have access to a pertussis antigen currently. If we combine those, we'll address those two key pathogens, because the maternal vaccination that's currently given in DTP really only protects the child against pertussis. That's why we think that is critical. In terms of SHINGRIX going forward, again, there's a global opportunity. Luke will build on this as well. The U.S. cohort will be caught up at some point in time. As we've said, we have a long way to go to reach that point going forward. There's further opportunity in geographic expansion, particularly in China, as I referenced. Maybe, Luke, you'd want to build on that. Sure. I think you're absolutely right, James. You've got similar numbers that you have with PCV. Older adults is where the main effort needs to be with RSV. If you look at maternal, from memory, penetration rates, around 60% at best in the U.S. There are lots of synergies in terms of pediatric purchasing within offices in the U.S. that we can take advantage of. In terms of the U.S., it's around 25 million patients have been dosed with SHINGRIX so far. Contrast that with Zostavax. Over all those years of 22 million. That's the advantage here of being free in terms of capacity. Our aim in the short term is to preserve pricing power with SHINGRIX in the private pay market. Once we exhaust that opportunity, we have that flexibility to expand into emerging markets at different points through UMBs, as I mentioned earlier. There's lots of optionality for us going forwards, but we will exhaust that cohort in the U.S. at some point. Similar numbers. If you look at urban numbers in China, it's actually just over 100 million people who are urban-based, above 50 years of age, who have the capacity to pay out-of-pocket for SHINGRIX. Deborah. Thank you. To answer James's question, I'm going to split it into two different parts. I'm going to talk about treatment. I'm going to talk about prevention. In terms of prevention, we obviously see this as a market that's going to grow rapidly. Most of the value will sit in the U.S., and for us, about 90% of the value by the time we get to 2031 in the prevention space will actually be in the U.S. Prevention is going to be very dominated by the U.S. Generics coming into Europe or the U.S. is not really going to impact that because we believe that the long-acting has such a strong value proposition in prevention that payers will be willing to pay. What we've got today in terms of orals is not necessarily working, and more tools are needed. You've only got 200,000 people taking PrEP at the moment in the U.S., and 1.2 million people probably should be taking PrEP. Actually, more tools are needed. We've got a fantastic medicine with superiority data in cabotegravir, and 90% of the value in terms of our business in prevention will actually be in the U.S. That's that part of the market. When you look at treatment, basically, we have very strong data supporting our long-acting portfolio, and we have very strong patient preference for our long-acting treatments. We believe that despite oral generic competition, both in Europe and the U.S., we've still got a strong value proposition. It will be more skewed towards the U.S. than where we are at the moment with dolutegravir where the split is more balanced. We do believe that given in the U.S. only 50% of people who are taking medication are actually virally suppressed in the U.S., again, there is a need for a lot more tools, and we believe that our long-acting medications are important tools which prescribers are very keen on, and there is a strong patient preference for. Thanks. Next question, please. Your next question on the line comes from the line of Matthew Weston from Credit Suisse. You are live on the call. Please go ahead. Thank you very much. Three quick ones, please. Largely points of clarification. The first on your non-risk-adjusted peak year sales. For the opportunities which would cannibalize your own products like MenABCWY and depemokimab, are those peak sales numbers incremental to your current revenue, or does that we have to assume cannibalization as part of that? The second question on the flu aspirational target. I think I heard Roger say that both plant and mRNA approaches were Upside to your 2031 ambition. Can you confirm I heard that right? Is that because you don't actually have commercial rights yet from Medicago and mRNA isn't in the clinic? I'd be very interested. Finally, just a quick one. I'd be very interested in your assumption for BENLYSTA biosimilar entry within your 2031 aspirational target. Many thanks. Okay. We'll go to Roger first on Medicago, and then Luke, perhaps, to give you some questions. If you could comment on any assumptions on the, was it the BENLYSTA biosimilar and then also the non-risk-adjusted sales cannibalization. First, quickly to Roger, because I'd like to get one more question in before we close out. Yeah. I can be very quick just to confirm that is exactly what I said, that our flu ambition is not included in the GSK long-term number that we have shared to date. Why? Well, because we believe that there is still some activity to go to close out the Medicago commercialization I mentioned, but also the mRNA piece as well. It is an early asset which will go into the clinic, as I said, in the next 12 months, but that we are allocating resources and very serious about the ambition, but it is not included in the GSK number that we quoted earlier. Thank you. Luke? The MenACWY is incremental. If you look at depemokimab, really interesting. When we looked at patient surveys, and I remember this number very clearly, it was 87% of patients on a biologic would prefer to have a six-month regimen, which I think is quite intuitive. A lot of opportunity there. Again, we know the target really well. The development program, I think, is very cleverly created, particularly the switching dimension. You've got patients who are stabilized on IL-5s. We can transition them. We can target Fasenra, for example, and move patients from two months to six months. Thank you. Just to reiterate, that target of more than GBP 33 billion doesn't include the vast majority of our early-stage pipeline. What we wanted to do today was make sure that we reassure on growth through the decade despite the dolutegravir loss of exclusivity. That was our goal with that. Obviously, we'll keep updating you as data reads out, the pipeline progresses. There will be some failures and hopefully lots of extremely exciting successes. This is just to answer that key question, which again, was one of the points we wanted to address today. Sorry, Luke, you wanted to add? Just to follow up on your statement around BENLYSTA. We have no intelligence right now in terms of biosimilars for BENLYSTA. I think structurally, if you think about replicating those results, lupus is an incredibly challenging environment to operate. The threshold for biosimilars is quite challenging. Thank you. Right. Last question for today, although I know we will have lots of chances to follow up with you tomorrow and in the weeks and quarters ahead. Last question, please. Your last question on the line comes from the line of Steve Scala from Cowen. You are live on the call. Please go ahead. Oh, thank you so much. Two questions. GSK believes it is the leader in adult RSV vaccines, but Johnson & Johnson has a very good vaccine that appears to be at a similar stage of development. Why does GSK believe it is in the lead? The second question is, I apologize for ending the call with a devil's advocate question that goes back to the basics. Today, GSK stated its commercial execution is industry leading. R&D productivity is top quartile. It has a leading HIV and vaccines portfolio. It has a differentiated strategy in immune- oncology, which I assume could be a GBP 50 billion opportunity. The guidance implies assets are in-house now that could drive peer average growth at least. Business development shouldn't be the highest priority. The dividend is still being cut. A leading consumer business is being divested, and management believes there is a need for a New GSK. These are extreme measures, although everything that was said today implies the former GSK was doing just fine. In this industry, extreme measures typically are not pursued unless when things are going well. What is the disconnect? What am I missing? Any help would be appreciated. Thank you. Let me take that multidimensional concluding question first, Steve, with thanks. I would refer you to one of my slides in my introduction. What we have been working on over the last four years has been a transformational level of change in GSK. A switch in strategy to shift our portfolio from around 40%, I think, in 2017 of our business in vaccines and specialty to being three-quarters vaccines and specialty by 2026. We've been addressing long-term legacy challenges. We know this has been a company that has perennially disappointed when you look at the first half of the last decade. In the last four years, we've been able to reverse the decline in top line. We've increased, very much necessarily increased our spend in R&D. Seen a real shift in our R&D productivity. Demonstrated in the last four years under the leadership of Luke Miels and Deborah Waterhouse, a definite step change in the competitiveness of our commercial execution. We are addressing questions of group structure precisely to create value for shareholders and unlock the strengthening of the GSK balance sheet and set us up for a step change in performance. That is the key commitment that we are making today, a step change versus our history and a commitment to competitive growth. When you look at the five-year outlook. We've really aimed to answer some very specific questions that shareholders wanted. What does this investment over the last few years, this significant amount of change, what does that translate in terms of commitment to growth, to commitments to profit? The answer is more than 5%, more than 10%, more than 30% margin, and more than GBP 33 billion worth of sales by the end of the decade. With that, you had a very specific question on RSV competitiveness in vaccines. Roger, would you like to close us out with that one, please? Yeah. Steve Scala, thanks very much for the question. Just very quickly, why we're confident is the technology and the proven technology. The J&J vaccine is a viral vector vaccine. The GSK RSV, which is the most progressed in terms of an RSV older adult vaccine, is built off our adjuvant platform. It's a pre-F antigen, which we know well. It's also using AS01. That's the adjuvant that we use in SHINGRIX. We've seen the phase II data. We're excited by it. Not only have we seen the immune response, but we've seen the T-cell response, which we know is so important in this elderly population in terms of addressing age-related decline in immunity. That's why we're excited that we're building off a platform technology that GSK has used to disrupt markets in the past. We believe that we have a real opportunity to come in and set the bar here in terms of RSV older adults. It's a big opportunity, and it's one that we're going to absolutely maximize. Thank you, Roger. Thank you to everybody for joining us on this call today. I hope you've seen that we've laid out for you a clear vision for the future of New GSK. As you've seen, we have big ambitions for patients and for shareholders, and we are very confident in our ability to deliver. Thank you very much for joining us. We're looking forward to catching up with more of your questions in coming days, quarters, and demonstrating this delivery in the years ahead.