Okay, good morning. My name is Peter Welford. I'm one of the European pharma and biotech analysts at Jefferies in London. It's my great pleasure to be hosting the next company in this track, which is GSK, and it's our pleasure to have with me on stage here today, Tony Wood, who's obviously the head of R&D, the CSO of GSK. We're gonna get a fireside chat. If anyone in the audience has any questions, we are willing to take them. Just raise your hand, and we'll try and get a mic through, if we can, to people. But yeah, please don't be afraid if you want to. With that, let's kick off. So perhaps, Tony, first of all, obviously, you've been in the role now for, which for, well, over a year, but sort of 15, 16 months. Can you just talk about, I guess, since you started, what's been the notable changes, I guess, and, and, and what do you think, what's your opinion, I guess, and, and how you sort of shaped R&D since taking over the role? Yeah, thanks, Peter. So first of all, good morning, everyone, I'm delighted to be here. So, in terms of the highest level change, if you like, for me, it's the beginning of focusing our portfolio across the four therapeutic areas that we have. We've got 67 assets in development at the moment, and this is really the distribution across a vaccines portfolio that I'm very pleased with in terms of recent progress with Arexvy, for example. Through our core platform technologies in vaccines, Arexvy obviously building out on Shingrix's success with adjuvanted protein vaccines, then the mRNA and MAPS platforms, and shifting then into infectious diseases in HIV, supporting Deborah and the team at ViiV, and the progress we've made with ultra-long acting. I won't go into detail on all of it, Peter, I promise, and we can come back and dig in on any of them individually. Also in infectious diseases, the progress with bepirovirsen for chronic hepatitis B infection, and then in respiratory and immunology, a lot going on in the phase III space there with depemokimab, a long-acting IL-5 monoclonal, and of course, Nucala in COPD that we'll hear more about early next year. Then lastly, really reshaping oncology as an emerging part of our business with a focus on Jemperli and its characteristics in genetically defined cancers, particularly in women's cancers. Lastly, I'll just finish up by saying the shift over to Ojjaara for heme. Really, it's been a story of focusing across our core therapeutic areas, some additional changes with regards to decision-making and governance and alignment into commercial, and really building on the foundations that we've made in technology. Happy to dig in on any of those, but don't want to turn this into a lecture. Yeah, yeah. But perhaps firstly, I mean, big picture again for a bit. What do you think are the key sort of competitive advantages of GSK's R&D and the approach, and I guess how do you think you differ most versus some of the peers? Because I guess, you know, we've heard from a lot of companies at the moment reshaping R&D and the way they think about it. You know, how do you think GSK is differentiating? Yeah, and I mentioned earlier, Peter, I think first of all, the opportunity to bring the vaccines business into R&D, and without repeating what I said, I think we have a really strong core of platform technologies in vaccines, in infectious diseases, again, platform technologies for HIV in the long-acting area, the beginnings of a journey into oligonucleotides with chronic hepatitis B. And then in respiratory and immunology, really the focus on human genetics and functional genomics, building on top of our respiratory expertise and a growing presence in emerging areas like liver disease through NASH and in perhaps renal disease, et cetera, through Benlysta and the extension there from lupus. And then, I guess, you know, the other thing that we hear a lot from pharma companies, obviously, is the sort of balance of business development, if you like, outside versus inside. What are the sort of key areas of focus for GSK for business development, and how do you think about that? Yeah, I mean, look, we're very much looking within business development to find opportunities that are complementary with our internal capabilities. In terms of the spread of opportunities across therapeutic areas as that I've mentioned, and also in terms of the opportunity for us to apply our technology capabilities to enhance value and productivity. And perhaps I'll take Ojjaara as an example of that. Look, a great case for me of a bolt-on in oncology, where we were able to spot the opportunity within a molecule that clearly, from its phase II program, had, at that point in time, some mixed success. What was apparent from the profile of the molecule, though, when you look at its underlying science, is that you have this unique combination of both inhibition of the JAK axis, but also, modulation of the hepcidin axis, and therefore control of anemia. So you could see in the molecular profile of the compound, if you like, and in the majority of its clinical data in phase II, that there was an opportunity to execute a carefully designed phase III study that would really illustrate the credentials of that molecule. And I'm delighted to say that's exactly what we saw with MOMENTUM. The deal that we put in place was entirely configured around a second-line label, and of course, as I'm sure many of you know, we've been rewarded with the profile now with a agnostic label, with really dealing with myelofibrosis patients with anemia. And just to remind you, that's 40% of the population at baseline. So it's those types of deals that you should expect to see us do more of. And, let's shift then to talk about some of the programs. Let's start off perhaps with vaccines. Obviously, the older adult RSV vaccine has surprised everyone with the launch commercially, in terms of the strength of the first quarter of sales. Can you just talk a little bit, I guess, about how the vaccine is differentiated, particularly obviously versus your closest competitor and, you know, how that's playing out in the marketplace? Yeah. So, look, I would say at the highest level, of course, we're delighted with the efficacy proposition for Arexvy, particularly in the at-risk population. That differentiation for me, it's probably worthwhile just spending a little bit of time describing where the strength of that label comes from, and then I'll talk a little bit about future development. So, of course, this is a really good example of us using data technology, first of all, to understand the dynamics of the RSV season during COVID. That allowed us to run a phase III program at a global level. It also allowed us to call an interim on that program at just the right moment. What you see in comparison to our competitors is that although we immunized approximately similar numbers of individuals, 15,000 in each case, the quality of our data set, when you look at our ability to pull out efficacy against at-risk populations, the older populations, those with comorbidities, is so much stronger. We also have strong data supporting co-administration. I think what you can see is all of that playing through and then shared clinical decision-making and, of course, our presence in the respiratory channels. Anyway, we will continue to develop the label of that vaccine. We have excellent data in the 50-59 population, which from an immunology standpoint, looks just the same as the 60+ population, and I'm confident that we'll be submitting that, and we'll be ready for ACIP and next year's season. I guess, you know, you mentioned that, the next year's season and the ACIP. I guess another key question as well we'll get next year is the three-year data. Because we know, you know, we know this vaccine now protects you for at least two years. I guess, can you talk a little bit about when we can get the, you know, the three-year data will be available? And, I mean, how should we think about then evaluating these data? Yeah, I mean, I get asked that question a lot, as you might imagine. Might be quite important. So I think probably the most important thing to say is that we're running that right now. We will have information on three-year efficacy and on second-year boosting in time for ACIP next year. If you ask me to guess on, you know, is this gonna be once every two years, or is it gonna look like Shingrix? That's a tough question to answer in the context of, you know, animal models are not the greatest translational fidelity in this area. But I think it's fair to say that it's unlikely to be Shingrix-like. You know, we'll see when we get the data for ACIP next year, but I don't want to be called on exactly what it is because confidence in translation here is relatively low. Perhaps it's worth saying, I mean, just so people understand, I guess, the obviously RSV respiratory infection, but, I mean, the, unlike flu, I guess, this virus doesn't, you know, change. I mean, in theory, this vaccine could have long-term durable protection. That's right. It's not a sequence-varying vaccine, but remember as well, natural history is of multiple reinfections. Yeah. So I think it's important to recognize that. And in terms of the market, I perhaps do, I just talk about eligible populations rather than get caught on stuff that Luke might not appreciate me giving answers on. Obviously, there are in the range of 90 million Americans. Yeah That qualify for the vaccine. If we add the 50-59 label, I think you're adding another 14 million or so to that total. Yeah. Yeah. I know you mentioned Shingrix. Obviously, the shingles vaccine has been very effective and, I mean, now proven at least 10-year immunity. Can you just talk a little bit about some of the studies and life cycle management that you're thinking about for Shingrix? Yeah. So, first of all, of course, the greatest penetration at the moment for Shingrix is in the U.S. Ex-U.S., there's still an enormous opportunity, so we're running studies to underscore that. I was delighted with the recent data in China that showed 100% efficacy, and the deal that we have with Zhifei there will certainly help by expanding the opportunity for outlets for administration of that vaccine from about 9,000 to 30,000. We're continuing to explore the long-term efficacy proposition associated with Shingrix, and we'll see 12-year data on that next year, and within it, we'll also be looking at the nature of reoccurrence in the immunocompromised populations. That's clear. Let's move on to some of the other vaccines. Perhaps first of all, meningitis. So you've had a pentavalent combination vaccine, which has had recent Yeah Positive phase III. Perhaps can you just talk a little bit about, just for those that understand the value of this vaccine, I guess, and what, why you do the MenABCWY, I think I got this right, and how you, y ou know, how this compares to Pfizer? Yeah. So, let me try and do this quickly because it, this is the basis of probably a 20-minute lecture. So it's fair to say that meningococcal disease vaccination is complicated. This is a disease for those who don't follow it has lower incidence than seasonal respiratory infection, but mortality associated with infection is enormous. So it's all about protection. Typically, what happens at the moment in the U.S. is you are scheduled or you're an infant or a adolescent is scheduled to have a first immunization against a quadrivalent strain, MenACWY, at the age of 11. That's then followed at the age of 16 with an immunization against the B strain, MenB, and that's because the prevalence of B disease is greater in that 16+ population. Right now, the focus on B, though, is all about covering the broadest number of strains. Pfizer's vaccine recently got approval for a scheduling which required that you can boost with Pfizer's vaccine against the quadrivalent, but you can only boost with B. But you can't boost against B with their pentavalent. That, for me, is a statement of how important serotype coverage is for the B class. What we have in Menveo, in Bexsero, which is our B type and quadrivalent vaccines, are vaccines with an extremely long history of experience, greater than 80% vaccine efficacy, and in particular, in the B strain, much broader coverage, 110 strains. So what we're doing with our own MenACWY is making sure that the quality of that strain coverage persists into B strain coverage. ACIP have said they will not consider a complete reexamination of scheduling to simplify until 2024 or 2025. So I think we're in a good position, Peter, both with regards to having the predominant, and I think most effective B vaccine in Bexsero, and having the components of that then echoing into our 1st and 2nd generation vaccines, preserving, as I said, the importance of vaccine efficacy in that B strain component. Then, I guess moving on to another sort of big vaccine market, you also acquired Affinivax not too long ago, which brought with it a pneumococcal vaccine. Perhaps you can just talk a little bit about the timeline and how you developed that and what its potential advantage is versus the current components. Yeah. So again, pneumococcal infection has similar epidemiological characteristics to meningitis, so I won't belabor that point. But again, the strain coverage is the important issue, and in particular, for pneumococcal disease, it's serotype 3, which accounts for between 10%-20% of invasive infection, depending on which age group you're looking at. What we have with our technology is the only technology that brings effective immunogenicity against serotype 3. That's because you need a protein response to serotype 3, not a sugar-based response. All of the other technologies have only sugar-based responses. In addition, you find with the other technologies that as you add more serotypes, and really to get 90%+ coverage of all pneumococcal disease, you need to be in 30+ serotypes. As you add more, you lower immunogenicity. You can see that in the journey from Prevnar 13 to Prevnar 20. You can see it in the Vaxneuvance and Merck data. What we have, what we have with our platform is a preservation of immunogenicity. It's very clear in our early data and in addition, serotype 3 coverage. Now, we acquired Affinivax, I think 18-24 months ago now. What we acquired was an organization that had a supply chain fit for early-stage clinical studies. What we've been doing now is changing that to a supply chain that will cover proper commercial scale activity, and in the meantime, generating confidence in immunogenicity data, both in the adult and infant populations. We have both of those things. I'm confident that we'll be restarting our infant 24-valent study next year. We'll also be seeing the move into phase III for our adult 24-valent, and we'll see the first time in human studies start for our 30-valent vaccine. That. All of this represents about a year of acceleration relative to the case that we contemplated when we first did the deal. It feels like we could talk about the vaccines for this entire session. Mm. But just the last one we do think we need to talk about, obviously, very relevant to the company that was just in here before us, but mRNA. Can you just talk a little bit about, you know, GSK's mRNA strategy and, and how that fits into the vaccines portfolio? Yeah. So, obviously, we're doing this predominantly in our collaboration with CureVac. The way to look at this for everyone, just to sort of give you a sense, we're targeting the entry of a multiple valent RNA vaccine, including COVID, within a year of Pfizer and Moderna launching theirs. What we see in our early data, and I want to just be slightly careful about how much of this I describe, given that I want to be mindful of my friends in CureVac, is, I would say, data which are encouraging with a profile for immunogenicity and reactogenicity that is at least equivalent to that for which you see in our competitors. I'm confident that over time, as we add more sequence optimization and other opportunities, that we'll continue to improve on that capability. So I, and you'll see more from our phase II platforms in both flu and COVID, again, at the beginning of next year. Let's move on then from vaccines a minute, and perhaps you could just talk briefly about another anti-infective area, though, which I think is perhaps a little bit unique for GSK, which is you are actually looking also at antibiotics. And in particular, you've had some recent positive phase III data for gepotidacin. Yeah. I can't pronounce that word. I can. Call it gepot. Perhaps you just talk a little bit about that and why, you know, GSK is still pursuing antibiotics. Look, I mean, AMR remains a significant area of need. Gepotidacin would be the first new antibiotic in 20 years for uncomplicated urinary tract infection. We were delighted with the clinical data coming from gepotidacin in terms of strain coverage, particularly for E. coli strains, which are accountable for the majority of uncomplicated urinary tract infections. That helps with regards to resistance because the broader spectrum antibiotics that are currently used there, the fluoroquinolones, for example, cover a greater range of bacterial species, and therefore, the spectra of resistance generation is a more significant one. I would say the best way to look at our antibiotic platform and the overall strategy, though, is if you combine gepotidacin and tebipenem, another recent acquisition that we have there. It's more of a tuck-in that collectively is a great business for Luke and his team, but not something that I'm looking at as a significant strategic allocation of R&D resource. Then, you know, the other exciting program is hepatitis B. Can you, I guess, just briefly talk about the recent phase II-B results for bepirovirsen, and how those inform your thinking of hep B development? Yeah, sure. So, just for, I know this is an area that not everybody is very familiar with, so if you'll forgive me, just a couple of quick stats. So, 300 million people worldwide, chronically infected with hepatitis B. This is a silent killer. There are no significant functional cures for hepatitis B. Functional cure is defined by the ability to suppress viral DNA and a biomarker known as the surface antigen protein to below levels of quantification. Clinically significant functional cure is deemed as anything greater than 15%. What we have for bepi in a biomarker-defined population, so if you have less than 3,000 copies of that surface antigen protein that I described, then we have a functional cure rate based on our phase II studies, which is consistent with the definition that I've just given you for clinical significance. If you go below 3,000, you see an elevation in functional cure rate. We have through a range of phase II studies continued to underscore that conclusion. I'm resisting going into very detailed numerical endpoints because all of those phase II studies were essentially designed to develop a quantitative model to allow us to predict the impact of bepi at a certain dose and in particular populations. That gave us enough confidence to move bepi on top of nucleosides into a phase III program. This is the B- Well 1 and B- Well 2 studies. They're recruiting well, and as I say, our expectation that for the 3,000 or less population, our expectation is that we'll see a clinically significant cure rate there. We recently completed also a study called B- Together, in which we were looking at what happens if you take bepi, and then you follow on with interferon treatment. That study showed there was only a marginal improvement in functional cure rate with interferon of the order of about five percentage points. When you consider that it, unlike hepatitis C, interferon is not used in this area because the functional cure rates are very low at acceptable doses. So the way I look at that is, sure, I would have loved it if we got to 40%, but I'm pleased that I don't need interferon on top of bepi to preserve that functional cure effect, which is defined not only in the terms that I described it for, viral characteristics, but also something that has to persist six months after you stop dosing. What's really exciting for me is we've just announced a deal, with J&J on accessing their siRNA molecule, which suppresses viral DNA, in such a way that you can think about a sequential treatment, starting with their molecule and then following with bepi, that will take us beyond the 3,000 or less surface antigen population, which is about 40% of that 300 million, into the entire population. What it will also do is deepen the therapeutic effect that we see with bepi, and so give us the opportunity for greater functional. So let's move on then to respiratory. I guess we should flag, you know, that you'll be talking a lot more about this on the 13th November at a respiratory event that's planned. But perhaps we can, you know, we can just touch on, first of all, the, I guess, the sort of leading respiratory asset, depemokimab, the long-acting IL-5. Can you just talk a little bit about, you know, how that fits in and what the aspiration here is for that program? Yeah. So first of all, important to sort of stress the position that IL-5 occupies in treating eosinophilic disease, and let's just focus to begin with on severe eosinophilic asthma. So obviously, a significant part of GSK's more than 50-year heritage in treating asthma. What we have from our experience with Nucala is a medicine that safely reduces exacerbations, and importantly, on the basis of ongoing phase IV and related studies, is beginning to show in about 35% of the population clinical remission. That's really critically important if you consider for a disease that any particular exacerbation can land your child in hospital, can continue to have their disease progress and not reverse. So we've moved the proposition with IL-5 away from reduction in exacerbations and the reduced use of steroids. Nobody wants their 16-year-old on steroids into something that is meaningfully showing a direction to perhaps change the course of the disease. We have the greatest data set for the use of IL-5 and indeed other anti-inflammatories in severe eosinophilic asthma. And it's important, just to stress this, because you should think about these not just as anti-inflammatories but as molecules that control the balance between inflammation, healthy wound healing, and fibrosis. And so the fact that we have clinical remission for the IL-5 class, I think, is an enormous advantage. depemokimab takes Nucala, which is once a month, and moves it into a once every six months proposition. Great example of data tech there. We ran a phase I study, again, against the back of a sophisticated model for effect, and that gave us enough confidence to go into four parallel phase III studies, both in not only in severe eosinophilic asthma but in other eosinophil-driven diseases. Now, we'll obviously talk about respiratory for a while. We've got camlipixant for chronic cough and that, but I guess, you know, encourage people to listen on the 30th. Perhaps in the interest of time, therefore, let's just touch briefly in the end on oncology. Mm. Can you just talk a little bit about, you know, where GSK's oncology strategy is now, and particularly, I guess, to Jemperli, which I think, you know, is, is obviously proven to get itself a niche indication, or a niche positioning, should we say, in the immuno-oncology market? Yeah. So very much the oncology is an emerging area. The focus is on heme and women's cancers. Let's just go quickly into Jemperli's performance in women's cancers. The most recent data there is from the RUBY study. This is in first-line endometrial cancer, particularly in the dMMR population. This is a group of individuals whose genetic characteristics of their cancer mean that we see a more immunogenic status and therefore a more effective response. What we see from part one in that population is a fantastic outcome with regards to hazard ratio. And if you look at the Kaplan-Meier curves for the dMMR population, they're flattening out. So we've got transformative efficacy in first-line EC. And what you'll see us doing with Jemperli, this is the second example of a transformative result. The first one that hit the news towards the end of last year was in a smaller population in rectal cancer with a study called the Cercek study, which again shows that we are producing cures. So for Jemperli, you will see me continue to identify molecularly defined cancer groups where we can expect to see those sorts of effects, and you'll hear more about, excuse me, how we're planning to combine Jemperli with TIGIT and other members of the CD226 axis at the beginning of next year. But the focus is very much on looking for that sort of transformative efficacy, beginning in women's and bridging into other cancers. Very clear. More to come. With that, we've run out of time. Thank you all very much for attending, and obviously, thank you mostly for Tony for staging me. With that, we'll end the session. The next one will start shortly. Thank you all.