Okay, great. Good afternoon. I'm Eric Joseph, Senior Biotech Analyst with J.P. Morgan. Our next presenting company is Vir Biotechnology, and to start the presentation this afternoon is CEO Marianne De Backer. There is a Q&A session after the presentation. Just raise your hand, we'll get a mic over to you, and for folks tuning in via webcast, feel free to submit questions as well via the portal. With that, Marianne, thanks for joining us. Okay. Thank you. Thank you, Eric, and thank you, J.P. Morgan, for hosting Vir Biotechnology. Good afternoon, everyone here in the room in San Francisco and everyone joining on the webcast. I'm Marianne De Backer, and I'm the CEO of Vir Biotechnology. So 2024 is poised to be a truly transformational year for Vir, because we are looking forward to data readouts from our clinical phase II hepatitis delta program, our clinical phase II hepatitis B program, and our phase I HIV T cell-based vaccine program. During this presentation, I will share more about Vir's leading clinical programs, about our plans to move beyond infectious disease, and also about the strength of our solid financial position that underpins everything we do. I will be making forward-looking statements, so for more details, I refer you to the regulatory filings on our website. Now, at Vir, we have a very bold vision, powering the immune system to transform lives, and we aim to achieve this in two fundamental ways. One is through developing powerful antibody therapeutics, and secondly, through generating unique T cell responses in vivo through our T cell-based vaccine platform. Here's a snapshot of our 2024 top catalysts for this year. With trials on track for several data readouts, including those in chronic hepatitis delta and in chronic hepatitis B. I will be going into more detail on these catalysts during my presentation. In addition to these hepatitis catalysts, we will be using our world-class antibody platform, which is proprietary, and our T cell-based viral vector platform, to grow beyond hepatitis and grow beyond infectious disease. And as you can see, underpinning all of this is a strength of a considerable balance sheet. We aim to maintain that strength by really taking very prudent action, as we already did last year, to reduce our operational spend, and also to sharpen our investment focus on those areas where we believe we can get the greatest impact on patients and the greatest value creation. Our balance sheet also allows us to potentially invest in external innovation that can further strengthen our pipeline. Next, I want to draw your attention to our pipeline. It's a very broad pipeline with multiple programs already in the clinic, and five more approaching IND in the next few years. I hope you will agree that this is a remarkable pipeline for a company of our size and our age. Now, let's begin with having a look at chronic hepatitis delta. One of the most significant clinical development milestones for Vir this year, and also for patients, hopefully, is tied to the clinical progress that we are making in our SOLSTICE trial. Delta is the most severe form of viral hepatitis. It's caused by a tiny RNA virus. It's estimated, for those of you who, who might not be familiar, that about 12 million people in the world are diagnosed with hepatitis delta, and that there are over 60 million people not yet diagnosed, but living with the disease. And once you are infected with hepatitis delta, more than 50% of the patients die within 10 years of chronic liver disease, including liver cancer. So it's a very significant unmet medical need, and the standard of care is really falling short. We have an approach at Vir that is aiming to achieve a chronic therapy for chronic hepatitis delta that is aiming to really reach the best-in-class efficacy, best-in-class safety, and convenience. So currently, if you look at the therapies that are available for patients living with this disease, there's only one therapy marketed, and that is in Europe. And if you are a patient, you have to basically give yourself a daily injection for the rest of your life. And for those patients that can actually adhere to that kind of a therapy, less than 50% have a chance of a clinical benefit. And actually, only one in ten achieve delta RNA that is going to the lower limit of detection. So there's a lot of unmet need here. There's a lot of uncharted territory, and we believe that with the data that we have in our SOLSTICE trial, only in a limited number of patients, we have an opportunity to really become a leader in this space. So you might remember what happened in hepatitis C. In hepatitis C, there was a significant underdiagnosis until a very significant treatment came available to patients. That significant treatment with really good results acted as a flywheel for more diagnosis. Our belief is that also for hepatitis delta, if we can come up with a really considerable treatment, that this can act as a significant flywheel for more diagnosis. What you see here is a map of prevalence of diagnosed patients in the United States. You can use real-world data to look at where patients are based on their zip code in the United States. We are doing a lot of these analysis to really understand where are the data, where are the patients, who are they, so that we can prepare ourselves potentially to be as focused and targeted and as successful as possible for a potential future launch. But also to really understand and make sure that the patients that are already tested and diagnosed can potentially very quickly convert to a treatment that they really need. So here I show our data that we announced last year at AASLD as a late-breaker, for our-- from our phase II SOLSTICE trial. Very promising initial data in six patients. So what you see here is a chart of new 28-week combination treatment data that we are sharing for the first time here at J.P. Morgan. To orient you to this important graph, on the X-axis, you see the days of treatment, and on the Y-axis, you see the levels of delta RNA. It's a logarithmic scale. The black lines represent individual patients that are on monotherapy of either tobevibart, a neutralizing antibody alone, or elebsiran, or a siRNA alone. And the blue lines show you what happens when patients are transitioned to combination therapy of both of those investigational therapies. And again, while participant numbers are small, we see a marked drop in levels of delta RNA. Five out of six participants achieved undetectable delta RNA, and six out of six were below the lim... lower limit of quantification. In the words of Dr. Tarik Asselah, a very important KOL in the field of hepatitis delta, "If this result can be reproduced in a much larger group of participants, I believe this potentially once-monthly therapy could be transformative for patients." As you look at this data, it's really important to highlight that this is the fastest decline in hepatitis delta virus RNA ever observed with any kind of therapy to date. Notably, this combination regimen was administered conveniently only once a month. We are continuing to enroll more patients, and we are on track to complete SOLSTICE trial enrollment in the first quarter of this year. We are pleased to say that enrollment is actually really going very well. Thanks to the data that we shared in November at AASLD, there's a lot of physicians that are very enthusiastic about this potential treatment, and there's a high level of interest from both the patient community and the physician community. So what we are really looking forward to is the data readout in the second quarter of this year, so coming up very quickly, where we plan to report more data at a major medical congress. At that time, we will have additional data. As you can see here, 15 participants at week 12 and 10 additional participants at week 24. Should that data be positive, then in the third quarter, we will align with regulators on a design for a registrational trial. At the end of this year, we will then have the full data on 30 participants at the—for a treatment out to 24 weeks, so that will really give us the full picture. But again, depending on the outcome of the data in the second quarter, we will not wait until the end of the year to start working on registrational trial design and engage in dialogue with the regulators. So we could not be more pleased with the data that we have generated so far, and we are looking forward to sharing more during the course of this year. Now, let's turn our attention to our chronic hepatitis B program. The goal for chronic hepatitis B is a little bit different in the sense that here we are aiming to achieve a functional cure. So this is not a chronic treatment for the rest of your life, in contrast to delta. This is a lifelong control of the virus after a finite duration of therapy. And it is well accepted in the medical community that achieving something like a 25% or 30% functional cure would already be very transformative for the many patients that are living with chronic hepatitis B. So there's an estimated 300 million people that are living with this disease. Again, it's very, very significant, and up to 40% of patients experience very significant clinical consequence. Again, liver cirrhosis and liver cancer is really the unfortunate outcome for a lot of patients. We have here again, our two therapeutic candidates, tobevibart, which is an investigational neutralizing antibody and elebsiran, which is an siRNA, that are both potent antivirals and immunomodulators. Again, at AASLD last year, we brought together 11 of the top KOLs in the world, top hepatologists, and we had a discussion on what would be required to really achieve a functional cure in hepatitis B. It is well recognized now that you do need a combination of an antiviral and an immunomodulator, and that is what we have here with our regimen. So we believe that this combination can play a really critical role in potentially delivering high functional cure rates. I will now be talking about our preliminary data. So starting with the combination of elebsiran, again, our siRNA, combined with peg interferon alpha. What we showed last year is that at the end of treatment, after 24 weeks, about 5.6% of the patients showed HBsAg seroclearance. At 48 weeks, there was a marked increase, fivefold to around 26%. Then what we are really looking for is functional cure rates. And so the functional cure rate is defined as your sustained S antigen loss 24 weeks after end of treatment. And you see here that we achieved 16%, and this is one of the best results that has been shown to date in the industry. Then additional data that we shared last year is that we have, again, added our neutralizing antibody tobevibart to either elebsiran alone, this is the first column you see there, or elebsiran plus interferon alpha. And we only have data at this moment in time at 24 weeks of treatment. But you... What you can already see is that only after this short duration of treatment, there was a threefold increase in S antigen seroclearance. So what these data tell us is, first of all, that if you have—if you treat patients only with peg interferon, you typically only get somewhere between 3%-7% functional cure rates. What we get here by adding an siRNA is we get to 16%. And again, these are all comers, all kinds of patients. We haven't preselected them. What we then also show here is that if you add our neutralizing antibody, which has been engineered for immune engagement, so the Fc domain has been modified to bind dendritic cells and elicit potentially a T cell response and really awake the immune system of these patients again against the virus, you can see that, you know, at least you have a threefold increase already at 24-week time frame. So the data that we are going to be showing at the end of this year is end of treatment at 48 weeks, and we look forward to that data. And then in the course of next year, in the second quarter of 2025, we will be able to share with you the functional cure rates of these doublet and triplet regimens. So these are the critical catalysts that I just discussed. So we completed enrollment of a considerable number of additional patients already in the third quarter of last year. So we have 50 patients in the combination of tobevibart and elebsiran. We added 30 patients in the triple combination, so tobevibart, plus elebsiran, plus peg interferon alpha. As mentioned, for these patients, cohorts, we will have 48-week end of treatment data at the fourth quarter of this year and functional cure data in the course of next year. Okay, so let's now turn our attention to our next generation research and development. Our core capabilities at Vir include deep expertise in immunology and virology, a world-class antibody platform that has now been improved with AI-driven protein engineering. As I mentioned, we have a T-cell-based viral vector platform to elicit long-lasting immune responses. And as you probably well know, Vir has a track record of discovering really impactful antibody therapeutics, and two of these therapeutics have gone all the way to patients and have been commercialized. What we now want to do is take these unique capabilities and deploy them to, of course, broadly in infectious disease, but also beyond that. Here you see a depiction of our proprietary drug discovery and protein engineering platform that really enables us to discover best-in-class antibodies that have been optimized for success in clinical development. Our platform, as I mentioned, has already generated two powerful commercial medicines, and there is much more to come, thanks to a now AI-powered engineering, where we can really look at, in parallel, at coming up with antibodies with increased potency, increased breadth, better PK, better manufacturability, increased half-life. So we can really optimize now in a much faster way, using a collection of different models. Now, how exactly do we do that? I will not go into detail here, but basically, we are using a collection of open source models and proprietary models that-... You know, together in parallel can be used to from a starting point antibody, again, optimized in parallel for a number of different parameters and characteristics that we are looking for. And you see here a couple of examples of where we have used that to either, you know, get antibodies with improved PK or improved potency. And one example that I wanted to just briefly show is VIR-7229. So you're all familiar with the fact that Vir Biotechnology was one of the companies during the pandemic that, in 15 months' time, went from just an idea on paper to bringing an antibody against COVID, a prophylactic antibody against COVID, all the way to patients. And more than 2 million doses of sotrovimab, Xevudy, outside of the United States, were delivered. What we did here, using our AI engine called Daisy, is try and see how we could create the next generation COVID antibody that would be really variant-proof. And what we have been successfully showing now is that VIR-7229, in vitro, is active against really the next generation of variants that are circulating today, such as, for example, JN.1, which is now 60% of the variants that are circulating in the United States. This is a program that has been supported by BARDA funding, so we were awarded $50 million from BARDA to progress this program beyond phase I. Beyond VIR-7229, we have a number of other prophylactic antibody candidates. One is for influenza A and B prevention, VIR-2981. The other one is for RSV, MPV, again, prevention. RSV and MPV are actually the most significant respiratory viruses that cause mortality and morbidity in infants, and we have designed a dual antibody against these pathogens. And then finally, we have an HIV cure, so this is not a prophylactic, but really a treatment. We have used our AI capabilities to come up with a very unique cocktail of neutralizing antibodies that hold the potential to be curative for HIV. And of course, this is very early stage, but this is really sort of bringing all the protein engineering and the knowledge in this field to bear from the Vir discovery team. So we will be sharing more about these programs and also timing of IND submissions during the course of this year and next year. So these are our antibody candidates. We also have 2 T-cell based viral vector candidates that I will briefly discuss. Our T-cell based viral vector platform utilizes a human CMV virus as a vector to actually elicit a very unique and potent T-cell response in vivo. Basically, you're using CMV a little bit as a Trojan horse that can bring in certain genes of a virus into the cell, and then elicit, again, a CD8 response. Based on in vivo data, we hypothesized that such a CMV-based vaccine may be able to program unique T-cell responses to protect people, really have a prophylaxis effect against HIV. This is a program that is currently in phase I, and this year we will be sharing, in the second half of this year, proof of concept data from this program. VIR-1949 is a program that is looking at using the same vector, the same CMV vector, but really a treatment looking at potentially using high frequencies of antigen-specific effector memory T-cells to reverse dysplasia in HPV-associated cancers. We received already up to $80 million in funding from the Bill and Melinda Gates Foundation for this program, and we were also very pleased to see that Nature recognized our phase I trial in VIR-1388 as one of the 11 clinical trials that will shape medicine in 2024. Finally, I want to talk about why we are poised to achieve our near, as well as our long-term goals, and that is due to a very strong balance sheet, as I mentioned in the beginning. We stand very well capitalized with $1.7 billion in cash and investments, as of the third quarter of last year, and this will allow us to fund through major inflection points that we have been discussing, for example, registrational trials in hepatitis delta and hepatitis B. Second, we are maintaining that strength by taking a highly disciplined approach to capital allocation, with a sharpened focus, as I mentioned, on the areas where we feel there's a highest potential for value creation. In addition, of course, again, our capital position gives us the flexibility to invest in external innovation, and we are looking at opportunities to further strengthen our pipeline. So in conclusion, Vir is well positioned to achieve our ambition of becoming a sustainable global therapeutics company, and we are well on our way to powering the immune system to transform lives. Thank you very much. Great, so we have a few minutes for Q&A. If you have questions, again, there are mics around the room. We'll get one over to you. Maybe Marianne and team to start with the HDV program. There, you noted that, at least as part of the initial evaluation of your regimen in this population, you know, the importance of gathering data in patients with early cirrhosis, with CPT-A class cirrhosis. Have the data that you presented thus far or that at the Liver Meeting, those include patients with cirrhosis, and I just wonder whether... I guess, can you just kind of speak to the relative tolerability profile of the monotherapy and doublet regimens in patients with some amount of cirrhotic phenotype? Okay. Thank you, Eric. I will start, and then I will ask Carey to comment further. As you have seen, we have now enrolled 30 new participants in the trial in two regimens, and this time we have included CPT-A cirrhosis patients. We did not do that initially. We again met with top KOLs from the world at AASLD. I think there's a high desire to include even more severe cirrhosis patients, but I think we have to be balanced in our approach and take this step by step. At this moment in time, we decided to include CPT-A, and then we will see how this goes going forward. Carey, you want to add? Yes, and, we've also been conducting a hepatic impairment study with both the elebsiran and tobevibart. And, you know, to date, at least in that study, we haven't seen any clinically significant changes in terms of the PK or safety profile in those patients through CPT- B. Okay. But at least having some initial data in patients with CHD would be part of the data readout in second quarter? In the second quarter. Yeah. Okay. Exactly, yeah. You know, if you're just kind of going off of the data, when you look at the HDV RNA profiles that you know you've presented thus far, it makes a really, you know, compelling case for upfront use of the combination in most patients. When do you think might be the earliest point at which you could kind of explore upfront use of that combination regimen, in which you necessarily need to generate those data ahead of beginning a phase III program? Carey? Yeah, sure. Yeah, so actually, you know, for what we showed in SOLSTICE to date was more of a lead in, so we wanted to look at the safety of each agent alone before initiating a combination therapy. However, since then, we've actually enrolled 2 additional cohorts, 30 participants each in each cohort, and one of the cohorts does initiate both agents together at the same time, and then the other cohort is looking at the antibody as a monotherapy. So we will have that data later this year as well. Okay, great. And can you just talk about sort of what your base case expectation is for what the approval path would look like in HDV? And sort of maybe what you're seeking to clarify perhaps around that expectation and discussions with FDA. Yes. So, as you know, the regulatory hurdle for hepatitis delta at this moment in time is actually really low. So the regulators are looking at a two-log decline in HDV RNA or below limit of detection and ALT normalization. However, the results that we have shown are really remarkable in the sense that we show that, you know, 80% of the patients, and again, it's only a small subset, it's only 6 patients, but 80% of the patients show that HDV RNA levels drop below the limit of detection and 100% below the lower limit of quantification. So we will have a conversation with the regulators as to what is the best primary endpoint for future trials. The other conversation that we need to have, and Carey can comment a little bit more, is what does the size of the trial and the duration of the trial really need to be? You know, to cover... I think in virology, of course, you typically do not need as many subjects to really see your efficacy effect, but of course, you need to have sufficient participants in the trial to show safety, and that will probably be determining this- Yeah ... the size of our registrational trial. Yeah. Yeah. Yeah, I mean, the goal of any chronic viral disease is to achieve undetectability in terms of viral load. And I think because, you know, the initial endpoint, combined endpoint for delta included that 2-log declines because we really didn't have great options. So if you look at our data, our baseline HDV RNA levels range from 3-6 log. But if you go from 6 logs to 4 logs, you meet that criteria, but that's still 4 logs of viral replication that's occurring that can cause, you know, inflammation or other disease. So I think with our data, if we're able to maintain and see more participants achieve this very high level of viral suppression, I think that would be very convincing and similar to that model. Getting to kind of the, you know, thinking about registrational trials and regulatory, of course, you know, that's all gonna depend on the dialogue that we have. But based on the precedents, you know, there is probably potential based on the, you know, based on the data, that you could get potential conditional approval after 24 weeks, and then full approval once you have additional follow-up there. So I think those are potential options that obviously we would like to explore. Okay. All right. Maybe just coming back to the expectations around, you know, what you might see in the cirrhotic patient population. I, you know, asked initially about safety, but I wonder whether or not the kinetics of viral reduction in that population might somehow be altered compared to the non-cirrhotic patients, either because of, you know, differences in baseline viral load or otherwise. Can you just sort of speak to that and maybe either non-clinical or clinical analogies that might give you comfort on seeing an adequate profile there? Yeah. At least, based on what we understand right now, we shouldn't probably likely see differences in terms of the kinetics of HBsAg decline between CPT-A and non-cirrhotics. But obviously, we will be gathering that data and learning from that- Okay. With these cohorts. Okay. Excuse me. We left you speechless. I like that. No, no, no, I think I have a pretty good sense of the picture in HCV. In HBV, I'm curious to just, you know, get a sense of the feedback that you're getting from the virology hepatology community on the evolving, you know, pattern that you're seeing. I guess there'd be sort of an expectation that, you know, well, certainly longer outcomes could improve with longer time on therapy. But let me just kind of, you know, pause there and get a sense of the type of physician feedback that you're getting on the liver data in that setting. Yeah. So, I mean, it's well recognized that, you know, HBV has not been an easy path, right? So I think what is certainly promising, and what KOLs appreciated... And again, I don't think we would be able to attract, you know, conversations with so many hepatologists if it wasn't that we are showing really, you know, that things are moving in the right direction. We see that if you add our siRNA on top of interferon, there is additional response. If you add our neutralizing antibody on top of our siRNA or on top of our siRNA plus interferon, you see again an increased response. So data are moving in the right direction. There's, of course, a lot to be shown and proven, but at least, you know, there's the signs that things are happening and that a siRNA as a mechanism of action, combined with an antibody that has been engineered for immune engagement, can have an effect. You want to add? Yeah, no, I think you covered it very well. Okay. Well, may I ask a bit of a provocative question? So let's assume the liver is infected widely with the virus, and the response efficacy is extraordinarily strong. What is the risk that you would see an acute liver failure at a very extreme end of response? So, hepatolysis. So your question is, if we achieve, say, a functional cure of 90%, is there a risk that you would have, you know, hepatic decompensation due to kind of the turnover of hepatocytes or the... Yeah. So I think, at least to date, with what we're seeing, even in our trials, where we're seeing up to 25%-30% of participants that are achieving zero clearance, and then about 15%-16% that are seeing that durability off treatment, we are not seeing kind of evidence of kind of ALT flares or other signals of kind of hepatic dysfunction or inflammation. And even if you're able to—if we're seeing, like, 25%, you would expect to see, you know, a small proportion maybe to kind of have that signal, but we haven't seen that to date, as well, so. So I don't anticipate having, like, a decompensation type of event. Thank you. Yeah. Yeah. I'm actually wondering: How long did it take you to recruit your entire hep B patient cohort? Which one? For your hep B trial. Yeah. So the way we designed our trials is we have, you know, multiple cohorts, more small kind of number of cohorts to rule out regimens that may not work. So it's kind of hard to—'cause we have so many different iterations, it's hard to say. But, you know, we have recently enrolled 50 into the elebsiran tobevibart arm, as well as 30 into the elebsiran tobevibart and interferon alpha arm. And I don't know off the top of my head, but it occurred relatively quickly, you know, over several months. But it all depends on kind of the number of sites and where you go, so it's kind of hard to- Is there a reason why you didn't go into Asia to recruit? Because that's where a higher hep B prevalence is. We do have sites in the, you know, Asia-Pacific region, but our partner, Brii, is conducting trials in China with these agents as well. So we have different footprints there. Maybe I could just ask a question about sort of the what's called next generation portfolio of antibody candidates that you highlighted towards the end of the presentation. You know, I guess, you know, yes, healthy balance, your position, but just how should we be thinking about the level of investment being allocated to those programs? Perhaps, you know, prioritization among them, and finally, whether they sort of might be opportunities for business development. Sure. And when? Yes. Yeah, so first of all, as I mentioned, our next generation COVID antibody is not where, you know, our investment is going. This is really a BARDA-funded program, and of course, potentially very important for future pandemic preparedness. As it relates to our other antibodies, the flu A/B prophylactic antibody and also the RSV MPV antibody are collaborations with GSK. So we share costs and obviously, upsides together with our partner there. The program that is fully owned and that we fund 100% is the HIV cure cocktail. And again, that's a very early program, but something that, you know, could be very exciting and something that we think is really worthwhile pursuing. Then, as it relates to business development opportunities, our view is that it would be most beneficial for us as a company to look for early clinical stage assets or for assets that are close to the clinic to really further bolster our pipeline. But sort of investment priority, of course, remains with our most advanced assets, and we have some really promising data, as you have heard in Delta and in hepatitis B, and that is going to be our first investment allocation. Okay. I guess, any further questions from the floor? All right, I think we'll leave it there for time. So thanks very much, the Vir team. Thanks so much. Thanks, everybody, for tuning in. Thanks, everyone.