GSK plc (GSK) Earnings Call Transcript & Summary

Good day, everyone, and welcome to the Meet GSK Management: Getting Ahead of HIV Conference, hosted by David Redfern, Chairman of ViiV Healthcare and Chief Strategy Officer for GSK. My name is Cathy, and I'm your event manager today. [Operator Instructions] I would like to advise all parties, this conference is being recorded for my training purposes. And now I'd like to hand over to David. Please go ahead, sir.

Thanks, Cathy. Good afternoon, everyone. I'm David Redfern, I'm the Chairman of ViiV Healthcare and Chief Strategy Officer for GSK. I'm delighted to welcome you to our Meet the Management Event: Getting Ahead of HIV for analysts and investors. As usual, the presentation materials are available on gsk.com and were sent to people on our distribution list earlier today. I'd just refer you to Slide 2, which contains our cautionary and forward-looking statements. Moving on to Slide 3, which provides a summary of what we shall cover today. I'm delighted to be joined by Deborah Waterhouse, the CEO of ViiV Healthcare; and Dr. Kimberly Smith, Head of R&D for ViiV. The following 90 minutes will be divided into 2 parts. For the first 45 minutes, we will walk you through the shape of our HIV business, growth drivers, our continued innovation leadership and our pipeline. Following that, we will have plenty of time for Q&A. [Operator Instructions] I'd also like to remind you that this call is being recorded and that a replay will be available after the event. Moving on to Slide 4. ViiV Healthcare is a joint venture between GSK, Pfizer and Shionogi and is 100% focused on combating, preventing and ultimately curing HIV and AIDS. GSK and its predecessor companies have been at the forefront of HIV innovation over the last 35 years. GSK was proud to develop the world's first medicine, AZT, to develop -- to treat HIV infection in 1987, followed by the first fixed-dose combination, Combivir, in 1997. ViiV Healthcare was created in 2009 and is responsible and accountable for end-to-end commercial and scientific functions with now over 1,400 talented people dedicated every day to discovering, developing and commercializing medicines to treat and prevent HIV worldwide. ViiV also successfully leverages and is heavily reliant on GSK's infrastructure and platforms in areas such as clinical operations, manufacturing and back office. In 2013, ViiV launched dolutegravir, which transformed the treatment of HIV by becoming the world's leading integrase inhibitor, and continues to be at the forefront of our innovative portfolio today. Two years ago, we again transformed the treatment paradigm by launching Dovato, a 2-drug regimen powered by dolutegravir at the core. And within the last few months, we have launched Cabenuva, the world's first long-acting injectable for the treatment of HIV. So we have a long, a proud and a continuing history and dedication of leading innovation in HIV in pursuit of our mission to leave no person living with HIV behind. And with that, I'll now hand over to Deborah Waterhouse, the CEO of ViiV Healthcare.

Thanks, David. We are now on Slide 5. I'm now going to provide an overview of the shape of our business and the scale of the HIV challenge worldwide. I want to add how proud we are to be using positive and authentic imagery throughout this presentation of people living with HIV. Ale, whom you can see here, is living with HIV in Uruguay and features as part of a campaign we are leading to transform perceptions and address inequalities and stigmas which remain so pervasive. We are now on Slide 6. ViiV Healthcare continues to lead in HIV. We are a significant contributor to GSK sales and a driver of growth, reporting global sales of almost GBP 5 billion last year and GBP 3.5 billion to the end of Q3, representing a 4% increase at constant exchange rates. We continue to transform the HIV marketplace. Our broad portfolio consists of 16 antiretroviral medicines offering a wide range of therapeutic options for people living with HIV. Our strategy is to remain innovation leaders in HIV, achieve a mid-single-digit CAGR to 2026 and absorb the loss of exclusivity of dolutegravir in the latter part of the decade through the changing mix of our portfolio and the success of our pipeline. We've changed the approach to HIV treatment with the launch of our 2-drug regimens, Juluca and Dovato. And 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 in the treatment and prevention of HIV and will make a multibillion pound sales contribution. As we move into the second half of the decade, we anticipate seeing continued growth in our long-acting regimens with cabotegravir replacing dolutegravir as the foundational medicine in our portfolio. And we're excited by our early stage pipeline, which we believe offers potential for revenue renewal from 2026 onwards. This pipeline has recently been further strengthened by our exciting new collaboration with Halozyme and Shionogi and the new partnership we're working on with our existing partner, Janssen, for an ultra long-acting version of Cabenuva, which Kim will talk more about later. And finally, we remain motivated by the ultimate goal, a cure, which will one day result in a future free of HIV/AIDS. We are now on Slide 7. HIV remains a global health challenge with [ significant needs ], and our mission to leave no person living with HIV behind is a commitment [ to access ]. Across the commercial markets of North America, Western Europe and international, we have a clear and differentiated strategy that we're confident will grow sales, share and profit over the next 5 years. We will continue to partner with middle-income [ tender ] market to ensure a consistent supply of our dolutegravir portfolio. In 2020, lower and upper-middle income countries accounted for around 45% of our volume. For those living in the least developed countries, we provide royalty-free licenses to generics manufacturers, found a wonderful group of partners who ensure treatment reaches those who need it. As a result of our access strategy, of the 28 million people currently taking anti-retroviral therapy, more than 18 million are on a dolutegravir-based regimen. We are also delighted to have developed and are now distributing through partners, the world's first dispersible formulation for dolutegravir for children living with HIV, most of whom are living in resource-poor settings. We are now on Slide 8. Key challenges remain in the treatment and prevention market, currently valued at around GBP 26 billion. Despite heightened awareness, the WHO estimates approximately 1.5 million new infections per year globally with the burden remaining greatest in Sub-Saharan Africa. COVID continues to impact people living with HIV disproportionately. Over the past 18 months, we witnessed a significant reduction in the number of people being tested worldwide for HIV. The dynamic market has also been suppressed by the COVID pandemic. In the U.S., for example, we have seen that the naive market has been suppressed by about 10% and switch by around 40%. Across America, it is estimated that only around half of people living with HIV are virally suppressed. And there are still 38,000 new infections per year. HIV rates are suddenly high amongst people of color and men who have sex with men, and as such, there remains a pressing need for new approaches for treatment and prevention. The HIV population is aging due to advances in treatment and increased life expectancy, it is now estimated that 3/4 of people living with HIV globally are expected to be over 50 by 2030. Unfortunately, the quality of life of people living with HIV remains lower than the general population, and levels of stigma and inequality persists. We are now on Slide 9, which depicts Yulia, who is living positively with HIV in Russia. I'm now going to walk through the commercial dynamics, which drive our business today. We are now on Slide 10. We've continued to focus on excellent execution and building capabilities to ensure we successfully drive the uptake of our pioneering portfolio. We've done this through disciplined and rigorous investment allocation, and we've increased our levels of spending to drive customer-facing launch activities. We are focused on enhancing our sales force effectiveness with the result that our good standing outcomes are now consistently above the industry average. Our sales representative call activity is broadly back to pre-COVID levels. And the chart on the right side of this slide demonstrates our leading share of voice, which is about 50% versus the competition in 6 markets, a statistic which we believe underpins our strong momentum and share progress. We've transformed our digital data and analytics capabilities. Just one example of the impact this has created is around our digital share of voice and medical congresses, which is now double that of our closest competitor. We also have industry-leading U.S. payer capabilities, creating rapid patient access across launched brands, achieving 98% patient access for Dovato and 80% for Cabenuva, just 10 months post launch. We also have an industry-leading medical team building awareness and confidence with HIV physicians, evidenced by the fact that the volume and length of calls with customers actually increased during the pandemic. And we have also seen the rapid inclusion of all our launch medicines into major global guidelines. We are now on Slide 11. Strong commercial execution is driving the performance of our innovation portfolio. This chart shows that our innovation sales are tracking towards GBP 1 billion year-to-date at the end of Q3, representing nearly 30% of our portfolio and significantly higher than last year. This is an important milestone and a proof point of success of our strategy to shift the market from 3 drug regimens to 2 drug regimens. Dovato continued to grow strongly, building on the positive momentum since launch. We are driving strong growth in the U.S. and Europe, particularly in the switch market. Dovato is currently #1 or 2 in switch in key markets. And this is despite the suppression of the overall market due to COVID. We're particularly pleased by the rapid uptake of Dovato in Europe with the share of switch currently around 28%. Dovato delivered sales of GBP 533 million in the year-to-date to the end of Q3 and is on track 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 [indiscernible] of the potential sales in the U.S. and the remainder split between Europe and international. Dovato is patent-protected until at least 2028 in the U.S. and 2029 in Europe. We are now on Slide 12. As Kim will reinforce shortly, HIV physicians are guided by data and guidelines, and we could not be more proud of our robust and industry-leading studies. The groundbreaking GEMINI trials demonstrated the viability and potency of dolutegravir plus lamivudine as a 2-drug regimen for naive patients. SALSA and TANGO swiftly followed, demonstrating high levels of efficacy and safety for people living with HIV wanting to switch regimens. Since then, our comprehensive clinical program for our 2-drug regimen portfolio has continued to demonstrate that Dovato is the best version of a dolutegravir-based regimen with fewer drug-drug interactions and reduced exposure to ARVs. We now have more than 3 years of efficacy and safety data for Dovato, which sets a very high bar for oral treatment regimens. The U.S. and European treatment guidelines include Dovato as recommended for most adults living with HIV in both naive and switch. Physicians report similar levels of confidence in their real world experience. We have almost 90 investigator-sponsored all real-world studies underway with Dovato. To date, clinical data has been presented on more than 7,000 people living with HIV, taking Dovato in naive or switch. As many of our physicians now say, a person living with HIV will be on treatment for the remainder of their lives. Why should they be exposed to 2 drugs when 3 -- why should they be exposed to 3 drugs when 2 is all they need? We are now on Slide 13. Cabenuva, the world's first and only long-acting injectable treatment for HIV, received FDA approval in January this year. It is also approved in Europe under the brand name Vocabria/Rekambys with dosing every 2 months. Cabenuva reduces dosing days from 365 to 6. It is powered by an integrase inhibitor and has non-inferior efficacy and comparable safety to daily oral 3-drug regimens. In our pivotal trials, 9 out of 10 participants preferred Cabenuva over daily orals, and the reasons behind these are clear. There are significant challenges with daily therapy, fear of HIV status disclosure, stress and anxiety about staying adherent and the daily reminder of living with HIV. Long-acting gives people freedom from the burden of daily oral therapy. And globally, more than 5,000 people living with HIV are now taking Cabenuva. We've launched in 11 markets, which account for 70% of peak sales, with a further 10 markets launching in 2022. We are seeing momentum accelerating in the U.S. with over 80% payer coverage, including a J-code in place from the 1st of October 2021, enabling a smoother, more automated reimbursement process. The prescriber base is increasing week-on-week. We initiated DTC TV advertising in October, which we believe will further stimulate patient demand. As with any new class of medicine, Cabenuva will take time to build. And the COVID environment continues to constrain switch activity, particularly where a patient needs to visit a physician's office. Despite this constraint, we are particularly pleased with recent progress as enrollment to the Cabenuva hub program have doubled since the beginning of September. We anticipate 2 positive label updates in the U.S., 1 for every 2 months dosing expected in December and 1 for optional oral lead in expected next year. Both updates will simplify the patient and physician experience. In Europe, we are also making positive progress having recently received an optional oral lead in label update from the European Commission. Next year, at AIDS 2022, we expect data from the SOLAR trial, a Phase IIIb head-to-head efficacy trial comparing Cabenuva and Biktarvy. We believe long-acting regimens are the future of HIV. And with at least a 5-year head start versus the competition, we expect to remain leaders in this space. We are now on Slide 14. Let's switch now to a strategic priority for our HIV business, the prevention of HIV infection, commonly known as PrEP. Cabotegravir for PrEP is a new long-acting injectable dose every 2 months for the prevention of HIV and offers the potential to transform the shape of the HIV epidemic. The FDA has given it breakthrough designation with a PDUFA date of the 23rd of January 2022. U.S. patient demand for a long-acting injectable for PrEP is high. The stigma around PrEP use and the perceived hassle of daily dosing are currently top drivers of discontinuation of PrEP. Prescribers express concern around their lack of ability to observe adherence with current PrEP options, and cabotegravir addresses these concerns. In the U.S., less than 25% of those who could benefit are currently taking PrEP. This is despite research currently published by the CDC which shows that many people are routinely engaged in behavior that could make them vulnerable to HIV, such as not using condoms, having sex with multiple partners or being treated for sexually transmitted infections. We believe the U.S. PrEP 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 to GBP 5 billion. The U.S. market is expected to grow further because there is significant motivation from prescribers and health systems to increase PrEP among people vulnerable to HIV, and 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. If approved, we believe cabotegravir will present a new and persuasive option in the PrEP market dosed every 2 months with superior efficacy to the current standard of care. We are now on Slide 15. I'll now walk you through the expected shape of the HIV business through the decade and our ambition to retain our leadership position as innovators in HIV. 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 generate around GBP 2 billion of our sales. We're excited by our early-stage development pipeline, which we believe offers potential for revenue renewal from 2026 onwards. 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 over to Kimberly Smith, Dr. Kimberly Smith, to take you through the transition to long-acting regimens and our pipeline.

Thank you, Deborah, and hello, everyone. We're now on Slide 16 and this fantastic image of Warren, who is living with HIV in Alabama. It's great to have another opportunity to talk to you about our exciting year and our continued role as innovators and disruptors in HIV. It's an appropriate time for reflection. This year, we observed the 40th anniversary of the first cases of AIDS. I began my career early in the epidemic, and I look back at that time as the bad old days. Young, mostly gay men were dying, and there were no treatments available. It was just over 30 years ago when the first antiretroviral for HIV developed by then Burroughs Wellcome was introduced. From then on, steady improvements in research has brought us new classes of treatment. And today, modern antiretrovirals has transformed the nature of the disease, changing it from a death sentence to a manageable chronic condition. Because of the significant progress in better treatments for HIV, people living with HIV are thankfully living long lives. But now they're facing new and evolving set of challenges, mostly associated with the cumulative effect of aging combined with being on antiretroviral therapy treatment for life. These challenges can include issues with tolerability, safety, resistance, dosing schedules, drug interactions and convenience. Over the years, patients have consistently asked us to find medicines that will give them options they need to overcome these challenges. And this has led a paradigm shift with the change to 2-drug regimens and long-acting regimens. At ViiV, we aim to take a deeper and broader interest in HIV and AIDS than any company has done before. That entails stepping beyond the development of innovative medicines and care for people living with HIV to research to better understand the barriers that stand in the way of getting to the end of the pandemic. Next slide. We're now on Slide 17. HIV has evolved. And as you can see with this slide, ViiV is leading that evolution. Let me walk you through our journey and our industry-leading pipeline, which is setting the pace for progress. It begins with our gold standard dolutegravir-based regimens, which have given rise to the innovative paradigm-changing 2-drug dolutegravir-based regimen. We're also the first company to deliver long-acting therapy and with the first approved long-acting 2-drug regimen. But our focus just isn't just on the broad population of individuals who are living with HIV, we focus on all patients. Our mission is to leave no person living with HIV behind. Our attachment inhibitor, Rukobia, is a perfect example of that. This is a drug that will impact much smaller number of lives, but it impacts individuals who have few or no treatment options left. And it's been incredible for us to experience the impact that Rukobia has had on individuals, literally saving their lives. So what's next? We'll continue to evolve long-acting regimens. We believe there's a lot of room for even better regimen. We want to offer a self-administered regimen as well as ultra-long regimens that will take us past dosing every 2 months to intervals of every 3 months or longer. And we'll do that with assets with new mechanisms of action, which I'll describe in more detail. We've also entered the prevention space. And just like we have with HIV treatment, we're transforming prevention and we're hoping in January to launch the first long-acting PrEP. But ultimately, we want to be a part of curing HIV Just as incredible to see HIV move from being a -- move to being a chronic manageable disease, but we won't stop until we see the end of the epidemic. Next slide. We're now on Slide 18. These have been at the cutting-edge of developing new options for patients. These are not accomplishments that happened overnight. We've been out in front of HIV since our company was created. And since that time, we've achieved a remarkable list of firsts: the first second-generation integrase inhibitor, the first approved 2-drug regimen, the first attachment inhibitor for highly treatment-experienced people living with HIV, the first approved long-acting injectable regimen for HIV, the first long-acting injectable for PrEP. And we've taken that first long-acting injectable for PrEP into the first head-to-head study of PrEP agents and show superiority of long-acting cabotegravir over daily oral pill. There are many reasons why we're first. We've built a company of people who are passionate about HIV. Remember, we're the only company that's 100% focused on HIV. And so if that's your passion in drug development and education, then ViiV is where you want to be. And that has fueled our culture with a united focus to deliver for people living with HIV. Our legacy in HIV is long. Our experience has allowed us to be efficient in moving products forward. And we've had multiple assets to choose from. We've also been willing to take risks and it's paid off. Next slide. We're now on Slide 19. I'd like to underscore what Deborah said earlier. We are now and expect to continue to be the leaders in long-acting therapies for HIV. We know this is the future because we've heard it directly from patients. Seven out of 10 people living with HIV told us that they're interested in a long-acting regimen because of the challenges that exist with taking daily pills. We've also heard from patients who are on long-acting as a part of our clinical trials. Within our pivotal trials, 9 out of 10 people prefer a long-acting regimen to daily oral. And the reason behind these 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. These are the unmet needs we're trying to address. What made me most proud was to hear from patients in our clinical trials that our long-acting therapy gave them freedom and liberated them from some of the anxieties that I've mentioned. It's been thrilling to be a part of that. Next slide. We're now on Slide 20. We pride ourselves on being -- on our strong relationships with patients, providers in the HIV community. What makes ViiV unique is the way we seek patient and provider insights and use them in our pipeline and portfolio strategy. Our confidence in the future of long-acting is based upon those insights, and I want to highlight a couple of people who have impacted our work. First is Patricia, who is in her 50s and lives in Germany. Patricia was diagnosed with HIV in 2005, so she's been living with HIV for almost 2 decades. And she's tired of taking pills every day. She doesn't want people to know she has HIV, so she keeps her medicine cabinet at home locked. What she wants to do is take her medicine as infrequently as possible. She wants to go to the clinic, get her treatment and then forget about it. For Patricia, an HCP-administered ultra-long-acting regimen could provide an even better patient experience with less frequent visits. Next slide. We're now on Slide 21. Next, we have Eric. For Eric, the future of HIV could be a self-administered regimen. Eric is 39. He lives in New York. He's not concerned about people finding out about his HIV status because he's out to his family and friends who doesn't mind having medicines in his home. Eric wants to control where and when he takes his meds, and he prefers not to come into the clinic every 2 months for a self-administered injection. So for someone like Eric, a monthly self-administered injection could be a regimen of choice. And that was reinforced with our market research where we heard that monthly self-administered injections were preferred overtaking a pill every day or every week. And they were preferred over clinic visits every 2 months. Eric doesn't want to be tied down. He wants to have the flexibility that a self-administered regimen would bring. These 2 patient profiles are of real people, and they're just a sample of those who have expressed their desire to have ultra-long-acting regimens, which we define as every 3 months or longer; and self-administered regimen, which could be given every month or longer. These 2 regimens, along with the long-acting regimen that we already have on the market, Cabenuva, which is administered every 2 months, would offer a comprehensive set of long-acting options for people living with HIV. Next slide. So when we build the next generation of long-acting therapies, how will we do it? Well, we'll start with the foundation of an integrase inhibitor, and here's why. Integrase inhibitors have proven themselves to be the unquestioned gold standard in antiretroviral agents because of their potency, tolerability and high barrier to resistance. INSTIs are now part of a preferred or recommended antiretroviral regimen in HIV treatment guidelines throughout the world. When we developed dolutegravir, we compared it to each of the first agents that were guideline recommended at the time. That list included non-nucleoside reverse transcriptase inhibitors, boosted protease inhibitors and first-generation integrase inhibitors. In each circumstance, dolutegravir demonstrated superiority. The use of integrase inhibitors has grown on the back of that incredible demonstration of efficacy, long-term tolerability, potency and high barrier to resistance. So the use of integrase inhibitors has grown dramatically as you can see on the chart on the right. From 2010 to 2021, the integrase inhibitor class has claimed 70% share across the top 9 markets. And I want to point out the dramatic trajectory that began in 2013 when dolutegravir was approved. Integrase inhibitors are now the gold standard. As a clinician, you want that trusted foundation when you're building a regimen. The field trusts integrase inhibitors and will not be quick to move away from them as an anchor for future regimen. The future of long-acting medicines is based with integrase inhibitors, and that's why we're building our next wave of medicines with our integrase inhibitor, cabotegravir. Next slide. We're now on Slide 23. So we'll start with an integrase and what will we do next? We will add a second agent. Cabenuva is cabotegravir plus rilpivirine. It's potent. It's effective. But for some individuals who have previously failed a non-nucleoside reverse transcriptase inhibitor, Cabenuva is not a treatment option for them. But we do need to have other agents with novel mechanisms of action to allow more people to take advantage of long-acting regimens. We have a very diverse portfolio of agents with novel mechanisms of action to combine with cabotegravir to create the next generation of long-acting medicines. We won't be taking all of these assets to late stage. But it's incredible to have this many to work with and ultimately to choose from. The graphic describes the steps in the HIV life cycle. We have a number of agents with novel mechanisms of action to attack many of these steps, and I'll walk you through them. Let's start on the left side of the slide with broadly neutralizing antibodies, or bNAb. There are antibodies that were identified in a rare proportion of the population that generates them naturally in response to the virus. These individuals generate antibodies that have the ability to neutralize not just their own virus, but neutralize a broad range of viruses. We have in-licensed N6LS from the NIH Vaccine Research Center. We chose this particular bNAb because of its great potency and breadth covering 97% of a broad range of viruses it was tested against and among bNAbs that bind to the CD4 binding site on gp120, N6LS was among the most potent. We've brought in N6LS into ViiV, and we're currently in Phase IIa, our proof-of-concept study. And we're really excited about the antiviral activity we're seeing in the preliminary data, which we'll be sharing in mid-2022. We hope to get the N6LS and cabotegravir combination into the clinic in 2023. The additional benefits of bNAb is that it could be a dual threat. It not only has direct antiviral activity, but it has the potential to enhance the host-immune response to the virus. Antibody attaches and identifies with the immune system, this is a cell you want to destroy. And that could help control HIV and potentially lead to a reduction in the latent viral reservoir, which is part of our work in the HIV cure space. We're excited about N6LS as a therapeutic agent, but also as part of the overall cure strategy. Next, we have 2 agents that are NRTTI. NRTTI have a 2-pronged mechanism of action, inhibiting translocations and acting as chain terminators, similar to other [ meds ]. Next is the capsid inhibitor. It's an important agent because it blocks the ability of the virus to make and break down the capsule that protects the blueprint of the virus as it transitions from the cytoplasm into the nucleus of the cell. Next is integrase inhibitor, which blocks the virus' ability to integrate viral DNA into host DNA. You'll see VH184 on this chart. And we believe that will be our third generation entity, and I'll tell you more about that in a moment. In addition, we have 2 formulations of cabotegravir. The current formulation is Cab 200, and we have a more concentrated version, Cab 400. We believe Cab 400 may be amenable for self-administration and allow us to use more products with lower volumes. And finally, we have the maturation inhibitor, which works late in the HIV replication cycle blocking one of the last steps in protein processing, [ the gag cleavage step ], which is necessary for creation of a mature virus. It's incredible to have this diverse group of agents to choose from and potentially to combine with cabotegravir. Next slide. We're now on Slide 24. We've mapped out the future of long-acting in our pipeline. For now, it's cabotegravir combined with this broad range of agents with novel mechanisms of action. And importantly, what this slide shows you is that many of these assets have the potential to be either self-administered or ultra-long acting, and they will allow us to have choices to find the best administered -- self-administered regimen and the best ultra-long-acting regimen. To be clear, we don't intend to develop all of these phases with cabotegravir, we intend to choose the best combination led by the science. And having multiple options to study is an enviable position to be in. Next slide. We're now on Slide 25. A lot of our success has come from our strategic partnerships. We selected excellent partners, and we think of ourselves as the partner of choice. We've had a long partnership with Janssen to develop Cabenuva. We're now exploring the possibility of expanding that partnership to evolve Cabenuva to an ultra-long-acting regimen, expanding the dosing from every 2 months to dosing every 3 months or longer. Just this past June, we made an excitement -- exciting announcement about a partnership with a life sciences company called Halozyme, and I'll explain on the next slide how that impacts our portfolio. And by now, most of you will be familiar with Shionogi, one of our shareholder company. And we've partnered with them on our successful integrase inhibitors, dolutegravir and cabotegravir. They will once again play a major role in development of our third-generation integrase inhibitor, which I'll talk about more in a minute. And one of our other exciting partnerships is the unique industry academic partnership we have with the University of North Carolina at Chapel Hill in the creation of a biotech called Qura. Our scientists work side-by-side with UNC scientists at the HIV Cure Center in the same lab, combining their early science expertise with our drug development expertise to find a cure for HIV. We hope to work with them -- we hope that our work with them will bring a latency reversing agent into Phase I study in 2022. Next slide. We're now on Slide 26. I want to talk to you a little bit more about the deal with Halozyme and why I'm so excited about it and what it brings to our portfolio. Halozyme makes a unique product we refer to as PH20. When PH20 is injected subcutaneously, it creates a temporary expansion under the skin, allowing increased volumes of medicine to be delivered subcutaneously without added discomfort to the patient. How does this translate to our long-acting pipeline? Well, with the ability to give a longer -- a larger dose, we'll be able to expand the interval between doses. The perfect example is cabotegravir. With Cabenuva, when we increased the volume of the injection by 50%, we double the interval between doses. So it's a 2-millimeter dose of cabotegravir for the monthly interval and a 3-milliliter dose for the 2 monthly interval. But that's the maximum dose that we can give without PH20. We believe PH20 will allow us to give larger doses. And with cabotegravir's long half-life, dosing regimens to be extended to intervals well beyond 2 months. That's the potential of PH20. This expands the opportunity for ultra-long-acting regimens combining cavotegavir with our pipeline products for treatment and for PrEP. We're looking to expand the dosing interval Cab for PrEP beyond every 2 months, at least every 3 months in combination with PH20. The exclusive collaboration covers targets for nearly all of the assets in our pipeline. We're extremely excited that over the course of the next year we'll start to see Phase I study of each of these assets in combination with PH20. Next slide. We're now on Slide 27. Now let me share a few more details about our recent announcement with Shionogi, with whom we've established a 20-year heritage of developing integrase inhibitors for HIV. Our most recent collaboration with Shionogi is for a very exciting third-generation integrase inhibitor called VH184. The preclinical data has shown that VH184 has a high genetic barrier and a resistance profile that is distinct from dolutegravir and cabotegravir. Its long half-life may support its development as an ultra-long-acting medicine that could be delivered with infrequent dosing up to every 6 months. We believe VH184 could anchor the future pipeline of innovative, long-acting therapy for HIV beyond 2030 with an expected loss of exclusivity beyond 2039. This will be combined with our agents with novel mechanisms of action that I've described to you previously. Our preclinical studies for this asset are underway. We intend to initiate the first time in human study with VH184 by 2023. And we hope to have the next generation of integrase inhibitors to continue our pioneering leadership in this space. Next slide. We're now on Slide 28. Let's shift gears now and move from long-acting treatment to long-acting prevention for HIV. Deborah has described the expected increases in the size of the PrEP market. And importantly, the PrEP landscape has significant amount of unmet need. Globally, more than 50% of people say they feel burdened by the idea of having to remember to take a medicine every day to prevent HIV. And importantly, PrEP is not penetrated into the communities that need it most. 69% of PrEP users are white, just 13% are Latinx and 11% Black. Yet Black American and Latinx people represent nearly 70% of new cases in the U.S. We also know that while daily PrEP is effective, it's limited by inconsistent adherence. We know there's interest in long-acting PrEP. Our research shows us that those that are currently taking daily oral PrEP or those who have tried it and stopped taking it are still interested in long-acting cabotegravir. And the majority of people who have never been on PrEP have also expressed interest in a long-acting regimen. The presence of long-acting PrEP will allow us to reach more significant proportion of the individuals who could benefit from it. Next slide. We're now on Slide 29. People have said that they want long-acting PrEP for convenience. And while we can tick the box for convenience, what we can show most convincingly is the superior efficacy of long-acting PrEP over daily pills. You're aware of the data we've shared this past year from HPTN 083 and 084 studies comparing long-acting cabotegravir to oral daily Truvada in men who have sex with men and transgender women in 083 and cisgender women in 084. The data is outstanding. And as you can see from this graph, from the 084 study in women, the rising solid purple line represents increasing new cases on the Truvada arm, while the red dotted line across the bottom of the graph shows a much lower number of cases in the Cab arm. HPTN 083 had similar results. These pivotal studies demonstrated superior efficacy in men and women 3 to 9x better than oral Truvada. And both studies were stopped early for efficacy with all participants being offered the opportunity to switch to cabotegravir. This is unprecedented in HIV prevention. This remarkable data form the basis for our file with the FDA, which we completed in July [ producing ] both breakthrough status and priority review status and expect the regulatory decision January 23, 2022. If approved, we believe cabotegravir will represent a new and persuasive option in the PrEP market dosed every 2 months with efficacy that is superior to the current standard of care. Next slide. We're now on Slide 30. So those data are really good news with people like Harvey, who is our third patient profile. Harvey is a 31-year old who lives in Florida. He's aware he might be vulnerable to HIV and wants to protect himself. He tried oral PrEP a year ago and had a hard time taking it every day and experienced some GI side effects. Harvey wants PrEP without the side effects he's experienced with oral PrEP. He wants something that's no hassle and is an easy fit with his busy professional and social life. We believe a clinic-administered injectable dosed every 2 months could offer certainty, discretion and long-term protection, characteristics that are often appealing to dissatisfied oral PrEP users. Next slide. We're now on Slide 31. I want to finish by talking to you about the time line for the delivery of our pipeline over the next decade, which illustrates the strength and breadth of our innovation. In the near term, in 2022 through 2023, we'll have a significant amount of data from our early pipeline. In 2022, you'll see Phase I data on Cab 400, Cab in combination with PH20, proof-of-concept data showing the antiviral potency of N6LS and Phase I data for N6LS in combination with PH20. In 2023, we'll see data delivery for our other agents with unique mechanism of action we've talked about. We'll deliver Phase IIb data for the maturation inhibitor 254 program. In addition, we'll see data for the NRTTI and the capsid inhibitor in combination with PH20. We'll also see proof-of-concept data for those assets. We also expect new data from Janssen on [ rilpivirine ]. Our expectation is that we'll be able to initiate our Phase IIb study of cabotegravir in combination with N6LS in 2023. By 2024, all the data that we've gathered between now and the end of '23 will enable us to make our partner selection so we can initiate late-stage studies in the 2024 time frame. That will allow us in '25 to '27 to deliver the first self-administered long-acting regimen for treatment. And also, we hope to launch an extended interval cabotegravir for prevention. From 2027, we expect to see a launch of our first long-acting regimen with dosing of at least every 3 months, anchored by cabotegravir with one of the agents with a novel mechanism of action. And post 2030, we're looking to have the next generation of ultra-long acting with dosing every 6 months anchored by our new third-generation integrase inhibitor, VH184, combined with an agent with a novel mechanism of action. Our ultimate goal is always a cure of HIV. It's certainly my hope and that of my team members that we'll contribute to getting there by 2030, if not sooner. Today, we shared our rationale for and our belief in our long-acting regimens as the future of HIV treatment and prevention. I've shown you what is the industry's most robust and innovative pipeline based upon years of success, experience and patient insights. I've shared with you the exclusive partnerships are going to help us build the next generation of long-acting regimens. And I've shown you that we are in the enviable position of having multiple assets to choose from to partner with cabotegravir, which will take place over the next couple of years and will take us through the next decade and beyond. Our strategic mission is to develop novel therapies for people living with HIV. Our company mission is to leave no person living with HIV behind. And our presentation today demonstrates our commitment to that mission. With that, I'll turn it back to Deborah.

Thanks, Kim. We're now on Slide 32. Our ambition is to get ahead of disease -- ahead of HIV, driving towards the ultimate goal of a cure. We shall do this by continuing to reshape the HIV treatment and prevention landscape, maintaining innovation leadership in the long-acting space. Through strong commercial execution, we expect to deliver mid-single-digit sales growth over the next 5 years. We will consolidate our multiyear head start in long-acting injectables for treatment and prevention with cabotegravir becoming the foundational medicine. Our exciting long-acting pipeline provides the opportunity for revenue renewal post the dolutegravir loss of exclusivity. And it offers people living with HIV freedom from daily oral medication and governments the ability to transform the shape of prevention efforts. And with that, I'll hand it back to David to open up for Q&A.

Thanks, Deborah. And as Deborah said, we're now happy to open it up to Q&A. So I'll hand you back to the operator.

[Operator Instructions] The first question comes from the line of Andrew Baum.

A couple of topics, please. First, on R&D. I wonder if you could comment on whether you are seeing or are concerned about dose-dependent mitochondrial toxicity with either of your NRTTIs in light of the lymphocyte reduction seen with Merck's islatravir. And then second, on the commercial topic, when I talk to infectious disease physicians, they cite the burden they have for frequent administration of IM injections in the clinic. So could you update us on how you're thinking about and how you would seek to implement the use of alternate injection sites or pharmacies in order to alleviate the burden? And then separately, when you talk about self-administered injections, I'm understanding this Cabenuva requires refrigeration, given this patient population and the cost of these drugs, that doesn't seem to be desperately practical for many of the patients infected with HIV. So how can you speak to resolve that?

Okay. Thanks, Andrew. Well, let's start with your important question with Kim on the mitochondrial lymphocyte issue that Merck had potentially seen and how that may translate across. So Kim, why don't you start.

Thanks, David, and thanks, Andrew. Thanks for the question. With regard to the limited amount of information that we've seen on this lymphocyte reduction, it's hard to draw definitive conclusions without seeing a full illustration of the data. We've basically just seen really just a hint of it. That said, though, clearly, lymphocyte increases are the hallmark of HIV successful treatment, particularly elevations in CD4 cell count. And so blunted recovery or declines in CD4 is certainly very concerning. I know that -- I'm certain that Merck is working hard now to try to get to the mechanism of action. And you mentioned mitochondrial toxicity, I think that's probably in the differential of things that could be potentially causing this toxicity, but I think we have to wait and see what they find. So clearly, we have, as you saw 2 NRTTI in our pipeline, and so we will be watching with great interest as we understand exactly what the mechanism is and whether or not this particular toxicity is present with our agent. But I think at this point, it's a bit early to be able to draw a conclusion.

Okay. Thanks, Kim. Deborah?

So 2 questions for me that came out of your -- came from you, Andrew. So first of all, there's a couple of label changes that will be made in the U.S. and have already taken place in Europe. So first of all, the [ orally ] will become optional, so you'll be able to go direct to inject. So that's taking a little bit of the complexity that's there at the moment away. And secondly, we will be seeking a license in the U.S. as we have in Europe for the injection for Cabenuva to take place every 2 months. So again, that takes away some of the burden that's there at the moment because in the U.S., it's an every month injection at the moment. We are moving into alternative sites of care. There are actually many physicians, particularly in the bigger institutions are quite happy to undertake the injections of Cabenuva. It's actually a source of revenue for them. But in places where they're not happy, we do have local alternative sites of care which are available. And then in terms of pharmacy, we're exploring the opportunity to have Cabenuva administered in pharmacies. But we haven't progressed that at the moment because we're still working our way through getting the processes established within the large sites of care and obviously getting alternative sites of care set up. Third part of the question, refrigeration. So refrigeration hasn't been an issue in clinics and health care settings. We did go out and asked the question a patient, would you be happy to have a box that we know roughly how big it would be in your fridge which would need to be refrigerated between the time you picked it up from the pharmacy and the time that you actually took it? And that did not appear in our research to be a barrier because the people that will be appropriate and keen to adopt this medicine were people that were out with their family and friends and were not worried about anybody seeing it in the fridge for the period that it would be sitting there. But we don't expect it to be that long because you normally pick it up, bring it home and within a short period of time, administer.

I mean I think all I would add, Andrew, is it's definitely been -- it definitely requires some setup of the practices to run injectables and run the clinics upfront. Now we're seeing multiple clinics have all these protocols and processes in place. And as time goes on, I think the whole administration is less and less of an issue.

Can I add something there, David?

Sure.

Yes. I just wanted to add a quick comment that says -- in response to that question about alternative sites because we do have an implementation study that is currently underway looking at alternative sites, and so we will have some data that helps to inform how we can operationalize that in the most effective way. And then the issue around self-administration and refrigeration, I think it is -- I really want to underscore the point that Deborah made that there's sort of a unique population of individuals who want self-administered. And those individuals are folks who are more likely to not be sort of hiding their HIV. They're more out about it. Whereas the individuals that are currently speaking long-acting Cabenuva, for example, they want the privacy. And so there's different sets of individuals who are more ideal for either a self-administered product or an ultra-long-acting product.

Great. Thanks, Kim. Let's move on to the next question.

Thank you. The next question comes from Graham Parry of BofA.

So firstly, on Slide 31, where you're saying by 2024, you'll have done partner selection for the self-administered regimen and ultra-long-acting regimens to progress to Phase IIb and III. Can you just run us through what the options that you're testing or deciding upon are here? So the self-administered is that Cab 400 plus novel MOAs and for ULAs, that Cab -- or Cab 400 that's going into the Halozyme technology? And can I just confirm that the maturation inhibitor is not part of the ULA collaboration with Halozyme and why not? And then secondly, when do you expect to have first Phase III ultra-long-acting combo data published to the market? And then third and last question is big picture, just when you think through the long-term strategy in HIV beyond dolutegravir patent expiry, do you envisage that the long-acting portfolio that you have will see HIV sales materially above the 2027 level in 2030 and beyond?

Great. Thanks, Graham. Kim, why don't you talk about all the multiple options? I mean you gave an overview, but probably worth going through it.

Yes. So again, we're basing our long-acting regimens on cabotegravir. And so Cab 400 may be the best option for self-administered or maybe Cab 200. We're testing both. Our main point is that we have multiple formulations to meet the needs. And so whichever combination is best tolerated is what we will move forward with. And so we have the option, as you saw in the sort of what we call the sort of the triangle flood, you see many of these novel mechanism of action agents that we're talking about could be combined with Cab and self-administered, and some of them have the ability to be either self-administered or ultra-long acting. And so as we get more of that Phase I data, in particular, the Phase I data in combination with Halozyme, that's when we'll have a better idea about exactly which combinations are best for ultra-long acting and which combinations are best for self-administered. And as you can see, again, I've mapped out that time frame of when we're going to see that data, and that tells us that we should be able to initiate Phase IIb with Cab and N6LS in 2023. And in 2024, we'll initiate additional studies. And so I can't go into sort of any more detail than that without having data in front of me, which we will have, as you see, mapped out here over the course of the next year. So -- and I think the question that you asked about MI and Halozyme, so there, we decided from the beginning that we would not include that in our targets, but it is possible we will expand our partnership with Halozyme to include maturation inhibitor if we find that there's value in looking at that combination.

Great. Thanks, Kim. Deborah, do you want to talk about the shape of the business and particularly beyond 2027?

Yes, sure. So Graham, let me just take us back to the June business investor update that GSK did on the 23rd of June. Emma and Iain presented a picture which by 2031 demonstrated that GSK would be delivering around GBP 33 billion of revenue. So the first question I just wanted to answer before I dive into ViiV is that we are very confident that GSK can offset the loss of dolutegravir through the medicines that they have launched today and those that they're launching from the pipeline that they have. So that is very important. Within that GBP 33 billion, we obviously have Cab for PrEP and Cabenuva. But the early development pipeline is not part of that. It was separate because, obviously, it's a little bit early. So GSK is in a very positive place. Let me just talk about ViiV. We believe that if things evolve in the way that Kim's described, so we have our ideal regimen selected by '24, and then we deliver them within the pipeline -- within the time lines that you have seen on Slide 31, that actually there is a significant amount of revenue renewal that will have taken place by 2031 and beyond because we obviously are able to match Cabenuva -- cabotegravir with our new mechanisms of action, which have IP out until the end of the 2030s. And then the Shionogi integrase has IP again out to the end of the 2030s. So what -- I'm not going to give you a specific number today, Graham, but what I can say is there is an opportunity for revenue renewal if what Kim has described today comes to pass. But even if that didn't happen, it's really important to know that GSK are confident that they can get to that GBP 33 billion number. And the company writ large successfully moves through the dolutegravir loss of exclusivity.

And the one on the -- when you expect to have first Phase III ultra-long-acting combo data that we published externally to the market?

Yes. I mean, well, I think -- yes, I think you kind of have to follow along with that time line. And so if we initiate Phase III studies in the 2024 time frame, then we would have data in the 2020 -- late '25, '26 time frame depending on the speed of enrollment of the trial. And so that's when we would expect to have that based upon the time lines that I've mapped out there.

The next question comes from Laura Sutcliffe of UBS.

Firstly, a high-level question. You've got a lot of options in the pipeline. So could you just give us an idea of what you think the ideal long-acting portfolio looks like if all your assets look feasible? Do you want a product in every bucket of those increases to be competitive? Or are there a couple of key wins in there? So for example, like [ 6 months ] that you see as critical to overall success? Then on PrEP, it seems like the PrEP market could move to more of an on-demand model. Do you think you can stop that or shape it by offering the right long-acting products? I know you've got some great data, but I'm thinking more about how you translate that into uptake and use. And then lastly, just going back to your event in June, could you talk to the greater than GBP 2 billion that you envisaged by mid-decade for long-acting products, just tell us if you have in mind a split between PrEP and treatment?

Okay. Thanks, Laura. Well, I think Kim can probably best talk about what our ideal profile is for long-acting. Remember, we're trying to ideally create a long-acting self-administered treatment and a long -- an ultra-long-acting treatment as well as a longer-acting PrEP. But Kim, why don't you be a bit more specific on exactly what you're thinking?

Right. So when you think about what is an ideal self-administered regimen, it's one that actually is extremely well tolerated by the patients. So one that causes them the least amount of injection site reactions, that's basically easy for them to give to themselves every month at a minimum. And so that's the target profile that we have, really high tolerability, dosing of intervals of a month at least, if not longer. So that's, in a nutshell, what we're looking at for self-administered. For ultra-long acting, we really want to make a step up from where we are now, which is every 2 months. So every 3 months would be an improvement. That means visits 4x a year. Every 4 months would be an improvement, meaning visits 3x a year. But yes, we would like to get to every 6 months, that's a high bar. And I think, Laura, it's important to remember how far ahead of the competition we are. And so the ambition of our competitors that was articulated previously was to have an injectable regimen in 2027. Well, obviously, we have a long-acting injectable regimen in the clinic now. By 2027, we'll be bringing more injectable regimens that have improved profiles. And when I say an improved profile from an also long-acting standpoint, it means fewer visits a year, longer dosing intervals. So those are the profiles that we're focused on. And again, I think what is exciting is we have many choices. Andrew's question around the challenge that the NRTTI has had is a perfect illustration of why it's so important to have multiple classes in your pipeline, so that if one particular class runs into unexpected problems, that you're not lost. You have many alternatives. And so that's what's exciting about our portfolio is all of that diversity.

Great. Thanks, Kim. And I think on PrEP, we see huge potential to develop the market, particularly in the U.S. and a significant opportunity over time.

Yes, I agree with you. So just to describe the market in a little bit more detail, Laura. So you've got in the U.S., which is where most of the value sits, you've got about 1.2 million people who should be taking PrEP to protect themselves from acquiring HIV. That pool is currently about 200,000 to 250,000 people are taking PrEP. So clearly, there's a significant opportunity to kind of grow that market. But the question you were asking more specifically was, is it an on-demand market? And the answer is yes. You don't stay on PrEP for a lifetime. Generally speaking, you stay on PrEP for, say, 10 to 12 months when your lifestyle means that you're at risk and it would be wise for you to protect yourself. So that 1.2 million has people coming in as their lifestyle at that particular moment means they're part of that pool. And then you have people who are moving out of that pool, when actually their lifestyle changes, so maybe they find a partner or they get married or whatever and that risk is no longer there for them. But so think of it as a pool that's usually about 1.2 million people, but with those people coming in and out, and people taking treatment on average for about 10 to 12 months. And so our job is to obviously give people the opportunity to switch from the oral that they're on today onto the long-acting injectable because we've got such great data. But then over time, to expand the market because, as I said in my presentation earlier on, some of the places where HIV acquisition is at its highest are hard-to-reach groups, and we're looking to expand the [ coverage ] of PrEP in some of those hard-to-reach groups. And that's very much supported by the kind of the CDC and the NIH because that's the only way they'll reach those ending the epidemic targets that have been set. The third thing you asked me was about the split of the GBP 2 billion. At the moment, we're not going to split it out because, honestly, Laura, I'd like to tell you that I was really that good at forecasting. But it's really hard for new products that are going into clinics, the new processes and everything to be kind of implemented. So we're pretty confident -- well, we are very confident in the GBP 2 billion. But the exact split, I'm not going to share because I'm not sure -- I think it's just a bit too early to do that. So as we get closer to '26, we'll definitely be able to be more specific on that and I'll be happy to share it.

I think what we can say, though, is both prevention and treatment for cabotegravir make meaningful contributions to it.

Definitely. And don't forget about the prevention. So the PrEP is all new revenue because we're not in PrEP at the moment. Whereas with treatment, we do take a lot of business from our competitors. I think at the moment, 53% of our Cabenuva is coming from Gilead. But it also is also cannibalizing some of our own business. So in PrEP, for us, it's all new revenue. So it means it's extra valuable, if I can put it like that. Thanks, Laura.

Great. Thanks.

The next question comes from James Quigley of Morgan Stanley.

You highlighted the [ 854 ] platform for 6 months treatment. And I'm just wondering if you could talk through the reasons cabotegravir, which was highlighted is for greater than every 3 months treatment from what you've seen so far. And what could be your base case expectations for VH184 relative to Cabenuva? And then on the HIV cure, where are you with candidate selection? And could you give us an overview of your approach and mechanism for -- approach of the mechanisms for latency reversals? You mentioned the broadly neutralizing antibodies could play a role in priming the immune response. What are your time lines in terms of when we could see the initial proof of concept basis from the study?

Great. Thanks, James. Well, we're very excited to have licensed the integrase from Shionogi, the next generation. I think it does have an important part to play. It's early, but Kim, maybe you want to elaborate a bit more on the reasons for doing the deal and what it might bring as well as James' great question about Qura, which we're definitely excited about, and there's lots of progress.

Yes. Great. Thank you, James, for the questions. So VH184 is a very exciting compound because it has a potency that we expect to be comparable to dolutegravir, and it has a half-life that is longer than cabotegravir, which is why we believe it gives us the opportunity to get to 6-month regimen. It also has a unique resistance profile that is distinct from dolutegravir and cabotegravir, and so it potentially could even salvage previous failures of integrase inhibitors. And so it is very exciting to see this. I mean literally, when we look at the profile of this product in comparison to something like dolutegravir and cabotegravir, and we see strengths above those, it's kind of hard to imagine. And -- but it's very, very exciting. So our intent, as I said, is that we're going to get this product in the first time in human as soon as possible. 2023 is -- by 2023 is the timing that we have in mind. And so I can't say much more than that because we don't have clinical data on this product yet. But again, the preclinical profile that we've seen is very, very exciting. In the Qura space, our work with Qura has identified a candidate, yes, it's [ Qura-086 ]. It is an IAP inhibitor. And it is a product that we candidate-selected and hope that by the end of 2022, we'll be able to get that into a first time in human as a latency reversing agent. For N6LS, we think about that as potentially an agent that helps with clearance. And so the concept of basically sort of inducing the virus out of hiding, out of latency and then finding a way to clear it. N6LS and other bNAbs has the potential to contribute in that space. And so that's essentially our approach.

Great. Perfect. A quick follow-up on cabotegravir and the potential dosing given what you said there with the long-acting or the longer half-life with the third generation integrase inhibitor, are you thinking that Cab 400 to potentially over 6 months? Or are you now sort of focusing more on the 6 months during the third generation?

Kim?

So we'll have data with all of the formulations of cabotegravir in combination with PH20. Starting next year, we'll see that data. And that will tell us whether or not cabotegravir can give us a 6-month profile. We are very, very confident that it can give us at least a 3-month profile. But can it get to 6 months? We can't know until we have that Phase I data. And we will test all the formulations in order to get to the best one that gives us the profile that we're looking for.

Thanks, James.

The next question comes from Peter Welford of Jefferies.

Just a couple. Firstly, just with regards to the DTC. Curious what was the trigger to begin the DTC advertising, given some of your comments you made about still decreasing the burden with the oral lead-in becoming optional and also the [ Q2 end ] I guess why start DTC now and risk potentially a poor patient experience, if you want to call it that, rather than potentially delaying, I guess, until you have then the option when patients come in to offer them the full package? But curious about any sort of comments you can talk about that. Secondly, then just with regards to PH20, again, pardon my ignorance, but do we have any long-term data on chronic use of PH20? I'm aware obviously you used it in a number of approved drugs, but I just wondered what the longest we have so far as far as chronic use of that as an agent within a combination that's injected. And then finally, just with regards to Qura again, but the idea of an HIV vaccine. Obviously, you have GSK vaccine expertise at hand. I don't think there is a vaccine against HIV. And I know it's a horrid history here. But is there any thought about that to ViiV or is that not an area that you want to be involved in?

Okay. Thanks, Peter. Deborah?

Thanks, Peter. So I'll comment on the first question really quickly. So the DTC that we have launched is targeted very specifically to geographical areas where we have got the health system up and running and already prescribing Cabenuva. So where we put the investment in DTC is in places where we know the patient journey is set up to be successful. So you do still have to go through the oral lead in, but actually, the early adopters are willing to do that. And obviously, the early adopters are also willing to go for an every month injection. But obviously, it is known in the community that it will turn into an every 2-week -- every 2-month injectable, if that was what the individual wanted later on. So we've been very targeted and very specific. But what is so encouraging is that literally in the last 8 weeks, we've seen the number of people that are enrolling in our hub, i.e., the physician has taken the person living with HIV through the process and is now ready to initiate. That's doubled in the last 8 weeks. So I'm feeling quite encouraged, particularly since we've still got the headwind of COVID. So that's a great question. Thank you for that.

Kim, do you want to talk about PH20 and what data there is in chronic use and also our thoughts on the vaccine?

Yes. Great. So probably the best example of long-term use of PH20 is in individuals with primary immunoglobulin deficiency. Those folks have been using PH20 in combination with supplemental immunoglobulin for years and in large -- very large volumes. And so there is quite a bit of experience with that along with other products. And so actually, the best place to see the long-term data for this -- for PH20 is actually on the Halozyme website where they describe all of their collaboration, and there is lots of examples of individuals that have been on it for years. With regard to the vaccine prospects, we're not currently in the vaccine space, but it's something that we're considering. And so it's possible that we could get into the vaccine space, specifically focused on a therapeutic vaccine that could go along with the rest of our Qura strategy.

Great. Thanks, Peter.

The next question comes from Kerry Holford of Berenberg.

Firstly, on the pipeline, clearly, you have much to work with as you show in Slide 24. But I just wondered if you believe you've got all the potential combinations that you would like to have dolutegravir in house or are there other aspects, mechanisms you would be interested in, in this HIV space that would mean you would consider external partnerships? And then just secondly, for clarification. You mentioned earlier, Deborah, the IP for Dovato expiring in '28 and '29 in the U.S. and Europe effectively. I wonder if you can just detail when in those years you expect the big IP to roll off, whether there is anything different here versus the [indiscernible] you have with dolutegravir [indiscernible]?

Thanks, Kerry. Well, we've certainly got a lot in the pipeline to be working on. But Kim, do you want anything else?

Well, as you heard, I mean, we really have assets in our pipeline that are attacking just about every target that's out there, but we don't stop. Our discovery teams are continuing to always look for new potential targets and new assets within the already identified targets. But we're always open to the possibility of partnership if it can bring about a new regimen that could be helpful for people living with HIV. We're always open to trying to move the field forward. So I would just leave it with that. Deborah, I don't know if you want to add anything to that?

No, that's spot on.

And IP?

So IP, so Kerry, the U.S. patent, if we assume that we're going to get pedia at 6 months, pediatric exclusivity, which the studies are underway, they'll report out in 2023. So we're confident that we will get that pediatric exclusivity, April, in the U.S., of '28, and then it's August '29 in the EU. You asked me a second question, there are additional patents, particularly on the 2-drug regimen. And that's why we say at least 2028 and 2029 because obviously, we do have additional patents and protection, and we'll just need to see how that unfolds around Juluca and Dovato towards the end of the decade. But in our modeling, we've assumed that the patents go August -- April and August '28 and '29, respectively. But we always fight for our IP.

And I think cabotegravir, for modeling, you can add 2 years to that for both U.S. and Europe.

2031 for Cab. But Cab is different because obviously, we'll have teamed Cab with other mechanisms which have got much longer IP out to the 2039, 2040. So that's why cabotegravir will be a little bit more protected, let's say.

Great. Thanks.

The next question is from Geoffrey Porges, SVB Leerink.

Just maybe just pivot a little bit to the U.S. market, very much your comments are focused on the U.S. market and particularly PrEP. And we've been wondering for a while how the payer environment might change in the U.S. Could you talk a little bit, first of all, about the mix of payers that you have in the U.S. today? And then secondly, how the transition to injectable is going in terms of coverage and particularly patient out-of-pocket cost? And then what, if any, impact would you expect Build Back Better to have if indeed it passes in the next couple of weeks to get through the Senate as is?

Okay. Thanks, Jeff.

So thanks for the question. So we have found that the data that we have for treatment with Cabenuva in the U.S. has been [indiscernible] for payers. And as a result, we have 80% coverage. And that's a mixture of Medicare, Medicaid and the commercial payers. So actually, I think we're in a very good position. In HIV, the out-of-pocket is actually very limited. So that's not going to be a barrier to uptake in the main. And just to remind you, 40% of our patients sit in commercial. 60% sit in ADAP, Medicaid, Medicare, et cetera. So, so far, we're in a good position with Cabenuva. And Cab for PrEP, we believe we have very compelling data and that we'll also be able to secure good coverage. But that looks like we're still in the middle of negotiating. But having superiority data from 2 studies is obviously very helpful. And given that the -- there is a focus on ending the epidemic, again, that gives us a lot of ambition around what we can -- what we're able to achieve.

And I think on Build Back Better, Jeff, I think it's all going to be in the detail as it goes through the Senate. And I'm sure the House -- as it goes through the Hill, both the House and Senate will probably make changes. So let's see how it comes out and then we can comment more fully. Okay. We've got quite a few more questions in the queue. And we will extend by a little bit. But if you could endeavor to keep to 1 question, that would help enormously.

The next question comes from the line of Simon Baker of Redburn.

Great. I will keep it to one. Just continuing with PrEP. As you've highlighted, PrEP is essentially a U.S. opportunity. I was just wondering how much of that potential doubling comes from ex U.S.? And how sensitive is the ex U.S. market and payers within that to the duration of therapy? I would have thought that as you increase compliance by moving to long-acting, it makes it a more appealing proposition. But I just wondered what the current perspectives are around the world on that.

Yes. Thanks for the question. So a majority of the value in the market today and in the future will come from the U.S. The reason that ex U.S. at the moment, the opportunity is limited is that payers are using and buying generic Truvada at about EUR 20 or EUR 30 or pounds a pack. However, what we are doing is talking to each individual country because there are still significant amounts of new infections across Europe, 22,000 a year. So to your point, Simon, what we're doing is sharing with them our data on adherence. And obviously, the superiority that we saw in 083 and 084 and putting together a case that this would be a good medicine to have available for those who are most at risk, and those dialogues are ongoing at the moment. But given that you've got a price point of generic Truvada that's so low, some countries are not going to be willing to fund Cab for PrEP. Others actually have demonstrated interest and have asked us to go and talk to them. So I think it might be a country-by-country price in Europe, but we're still having those dialogues today.

And there's some pretty powerful patient lobbies that may well...

Most of the value that I quoted today, GBP 4 billion to GBP 5 billion, the vast majority is in the U.S.

Okay. Thanks, Simon, for keeping it to 1 question.

[Operator Instructions] The next question is Elizabeth Walton of Credit Suisse.

I'm hoping we can dive a little bit more into your market research around desires for long-acting therapies. I know historically, you've talked about it being a niche group of patients that were seeking long-acting therapies. Today, you've highlighted that 70% of patients who are interested in long-acting treatments and 66% interested in PrEP. I'm just curious if you can give us a breakdown of those that would be interested in what's available today for treatment, so in-office administration versus future self-administrated long-acting options, both in treatment and in PrEP.

Thanks for the question. So I think when we've talked about this before was actually we talked about Cabenuva, the addressable market for Cabenuva being about 15% because obviously, it's 2 intramuscular shots every couple of months. So that's not going to be for everybody. What we know from our research is that every time you elongate the gap between administration or you're able to let people have control by administering at home, the amount of people who would be willing and would be keen to take a long-acting increases. And so you get more like to your 30% and 40% at that point as an addressable market. However, you've got to then filter that by what kind of payer coverage is available for those individuals or whatever the countries that they're living in whether or not the medicine is available. So the principle is the more options that you give, particularly the gap between the administration, the bigger pool that becomes addressable for the medicine goes up. That's treatment. In PrEP, actually, there's a much higher willingness to take the [Audio Gap] It's 1 shot, it's every couple of months, and you're only going to be taking it for probably 10, 12 months at a time. It's not a lifetime commitment. So we see the addressable market for long-acting medicines, especially with the superiority data, as really significant. So hopefully, that differentiates the 2. Kim, did I miss anything because I know this is something that you've got a lot of insight and passion about?

No, I think you nailed it, Deborah.

Thank you.

Great. Thanks.

The next question comes from Simon Mather of BNP Paribas.

Just one on the pipeline actually. Looking at your slide, you've got 2 NRTTIs and a capsid inhibitor, just wondering why you haven't tried potential combinations which would obviously mirror the ongoing, albeit paused, efforts with Merck and Gilead with islatravir and lenacapavir. And just a quick follow-on, if I could. Obviously, your pipeline looks like it's all based on the long-acting with an integrase at the background and all these are injectable products. I mean how should we think about GSK ViiV now? You talk about, from an ESG perspective, wanting to help the world. Obviously, injectables might be potentially a bit more difficult from a logistical perspective for third world countries, just thinking now how we should think about future efforts for the wider market.

Thanks, Simon. Kim, do you want to comment on NRTTI combinations?

Yes. So I think I've probably emphasized it quite a bit in the presentation is that we think it is critically important to have the foundation of an integrase inhibitor because the field has accepted integrase inhibitors as the gold standard and for all of the reasons that I articulated. And so we see the most likely future being start with an integrase inhibitor and add a novel mechanism of action. Certainly, we have 2 NRTTIs in our pipeline, 1 lead and 1 backup. Similarly, we have a lead and a backup capsid inhibitor. We'll see exactly what those profiles are and look, as I said, to combine those with cabotegravir and then later on potentially with VH184. But again, we think of long-acting regimens really having an entity at the core as the foundation is really more of an appeal to providers. Novel mechanisms of action are exciting. But the challenge with them is that you can sometimes have unexpected issues that will come up. And we really like the idea of having something that is established and trusted by providers as a foundation.

Thanks, Kim.

Yes. And Simon, to your second question. So obviously, we've been very successful, well, with dolutegravir. We have a policy to offer all of our medicines to generic companies for voluntary licenses. You are correct, the generic companies are not as willing or enthusiastic of taking up our offer on the injectables. So I don't think you'll see Cabenuva-type products in these developed countries, but there is an enormous interest in PrEP. And so what we are currently doing is putting together our models to work out if no generic manufacturers steps up to make a cabotegravir PrEP via a voluntary license, that we would step in, in partnership with [indiscernible], the Gates Foundation, et cetera, and we would be then the supplier of that preventative agent in the countries where it's most needed. So we are currently talking to many of the supernationals and the government in those least developed countries. And we are currently working out what volume would be required to support the effort to -- and the epidemic in those countries as well.

Okay. I think we just have time for one more question.

And the final question comes from Seamus Fernandez of Guggenheim.

This is Evan Wang on for Seamus. Just wanted to follow up on the NRTTIs. Can you talk about some of the internal work you're doing, the [ exploited ] mechanism that we've seen with islatravir? And then on that, how you see the kind of impact of what we've seen with islatravir in both the treatment and PrEP markets, if there's any differentiation between the 2?

Thanks. Kim, do you want to?

Sure. Well, so this is quite fresh news, this potential toxicity with islatravir. And so we have not yet introduced new safety efforts to try to understand the mechanism. But certainly, we will be watching very closely as that data gets presented. Again, we've only heard a tidbit of the data. And so we're looking to see the details. But we will -- and then we will map out our own program for how we would try to understand the impact of that -- of those results.

Great. Thanks, Kim. I think that brings us to almost the end of the call. So I'd just like to thank all of you for your participation. All I'd like to say in closing is we're incredibly proud the history of GSK and its previous set of companies over the last 35 years and what it's done in treating HIV and now turning it into a chronic disease that can be extremely well managed. But we're also equally excited not just about the past but the future. And I hope today has been helpful in setting out our vision for the future and particularly our long-acting pipeline, which I think we feel very strongly gives us the strong possibility of revenue renewal through the dolutegravir [ patent expiry ]. So we're excited to share that with you. We will obviously update you as we go forward and as the data comes through next year and into the middle of the decade. But thank you very much for your time, and appreciate you attending.

Thank you. That concludes your conference call for today. You may now disconnect. Thank you for joining. Have a good day.