Good afternoon, everyone, and thanks for joining us at the Morgan Stanley Global Healthcare Conference. I'm Mike Ault, one of the biotech analysts here, and it's my pleasure to introduce Marianne De Backer, CEO from Vir Biotechnology. Just a reminder, the format for today is a fireside chat, so if anyone would like to ask a question, please raise your hand. But before we get started, I just need to read a quick disclaimer. "For important disclosures, please see the Morgan Stanley Research Disclosure website at www.morganstanley.com/researchdisclosures. If you have any questions, please reach out to your Morgan Stanley sales representative." With that, Marianne, thanks for joining us, and I'll just hand it over to you to make some introductory comments, and then we can get into the Q&A. Okay, great. Thank you, Mike. Pleasure to be here again at Morgan Stanley. Yeah, maybe just to introduce Vir a little bit. So Vir Biotechnology, our vision is really to transform patients' lives through powering the immune system. And the way that we have been doing that, and we have, you know, a lot of experience in, for example, COVID and hepatitis, is by engaging the immune system one way through our platform, our antibody platform, where we do a lot of Fc engineering to again inducing immune engagement to fight against infection. And we recently announced a deal where we are acquiring a second platform that is focused on masking T-cell engagers. And again, the whole idea is there, that you unmask a T-cell engager so that only at the tumor environment, you actually bring together a T-cell and a cancer cell, and you induce the killing of the cancer cell through, again, T-cell-directed. So both on the antibody side and the T-cell side, we have technologies that we can bring to bear to help patients either fight infection or fight cancer, really through powering up their immune system. What I'm really excited about is how we are building a very compelling clinical pipeline. So we have a phase II program in hepatitis B that is aiming to get to a functional cure. We have a phase II program in hepatitis delta, where we're aiming to get to chronic treatment. And then through a transaction, again, that we announced a couple of weeks ago, we will soon have access to three clinical-stage T-cell engagers addressing metastatic solid tumors. So taking that all together, you know, we have, as I said, a very compelling pipeline that we're building. A number of data catalysts coming up. We will have a phase II end-of-treatment data for our hepatitis B program already in the fourth quarter. We will have a full data set on hepatitis delta in the fourth quarter. And then in the course of next year, we will have, you know, start of a phase I program in EGFR and data on our HER2 and our PSMA programs in the second half of the year. Yeah. A lot coming up. Yeah, a lot coming up. Yeah. And you've been busy also recently with the deal and some other announcements. So maybe. You know, thanks for that introduction, but maybe we could just start with, you know, you also announced the recent strategic restructuring and pipeline prioritization. So maybe just walk us through some of those changes and some of the reasons behind that. Sure. It might be beneficial in that context to talk a little bit about where Vir is coming from. So Vir Biotechnology was one of, you know, only a handful of companies that was able to bring a COVID therapeutic to market. Mm-hmm. And of course, you know, since the pandemic has ended, we were part of that subset of companies that had a rise and fall. Mm-hmm. associated with it. So, you know, one year we had over $1 billion in revenue, and the next year, basically, that revenue had dissipated. So obviously, when you find yourself in such a situation, you have to revisit your strategic imperatives. And what we have done is looked at, you know, how do we reprioritize our pipeline? What are the programs that we want to take out, phase out? And what other restructuring measures do we need to take? And so on the prioritization front, what we did is we said: Okay, our most advanced programs in the clinic, hepatitis B and delta, are really, you know, very promising, and we really wanted to make sure that those were going to get the most attention, and you know, the resources. And we also reprioritized our preclinical pipeline to only focus on RSV prophylaxis, which is a fifty-fifty deal with GSK, and HIV cure, because there we have a very unique, you know, cocktail of antibodies that we could deploy. So we really trimmed down our infectious diseases pipeline. As I mentioned, we also decided to phase out a number of programs. So we stopped our efforts in influenza prophylaxis, and we are in discussions with partners around that. We phased out our COVID program, and then we also phased out our viral vector-based platform and the associated programs, again, in HIV prophylaxis, in TB, tuberculosis, and HBV. As you know, as a result of all that, we looked at our workforce and how we would, you know, really fit our resources to what it is we need for the future. Taken together, you know, everything we have done since last year, we have reduced our workforce about one-third. As we will probably talk about a bit more, we are bringing some additional resources in through the transaction with Sanofi, but those are very focused on, again, bringing clinical-stage assets. Mm-hmm ... forward, in the pipeline. Yeah. Maybe just we continue with, you know, sort of the Sanofi deal, and maybe talk a little bit about just the rationale behind it and maybe some of the structure of that deal. ... Yeah, so maybe, you know, first on the structure, so it's an exclusive license agreement. So we get access post-closing of the deal to three clinical stage T-cell engagers targeting respectively HER2, PSMA, and EGFR. And we are also getting the exclusive rights to the Pro-XTEN platform, which is a masking platform for the fields of oncology and infectious diseases. And as I just mentioned, I think what is quite unique is that we're also bringing a group of about 50 scientists into Vir that have been associated with the programs, the clinical programs since the start, that have been working with the platform, you know, for over a decade, and that have deep expertise in how to, you know, manufacture those T-cell engagers. So the deal structure is, you know, almost like an acquisition, in the sense, again, that it's unique to get access to assets, platform, and the associated talent that you need to bring it forward. The way that we thought about this deal strategically is a couple of things. I mean, what made us really excited about it is, first of all, each of these assets address a really high unmet medical need. You know, if you look at just the PSMA program, for example, it is still the case that, you know, the five-year survival rate for patients with metastatic prostate cancer is only one in three, 34%. If you think about EGFR-associated cancers, five-year survival rate varies somewhere between 3%-38%. So again, you know, very abysmal numbers there of survival. And in addition, if you look at the modalities and the treatments that are available, a lot of them come with significant toxicity associated. Mm-hmm. Now, also for the T-cell engagers, while the T-cell engagers hold great promise, and there's, you know, 10 T-cell engagers already on the market, they typically come with, you know, significant toxicity, which, you know, sometimes cardiac dysfunction, interstitial lung disease, pneumonitis, and so on. So what is really unique about these T-cell engagers that we are going to license in, is that they are masked. So, they are only going to be activated in the tumor microenvironment, and that is, you know, giving a potential to be able to reach a very different level of therapeutic index, and hopefully associated with a much safer profile. Maybe you can talk a little bit more about the Pro-XTEN platform in terms of, you know, how validated is it? You know, how much experience is there? That kind of thing. Sure. Yeah. So Pro-XTEN, the name sort of, you know, gives away some things. First of all, XTEN refers to the fact that this platform was initially developed to extend half-life of drugs, and there is one drug on the market, by Sanofi, it's called ALTUVIIO, that is using the XTEN mask. So it's a hydrophilic mask that again has been able to be developed and is proven to be safe. The Pro refers to the fact that the mask is linked to a protease cleavable linker, and that is really the ingenuity of the technology. The T-cell engager that is, you know, containing the mask can travel in, you know, in the circulation of patients. Nothing much happens until the masked T-cell engager reaches the tumor microenvironment, and at that point in time, the linker can be cleaved by a number of proteases that have high activity- Mm-hmm. Only in the tumor microenvironment. And by only revealing the T-cell engager at that moment in time, you know, induce the cancer killing activity very, very specifically. Mm-hmm. What is also really unique about the platform is that every single T-cell engager, you don't need to start from scratch in, you know, coming up with a linker and a protease and a mask. So it's a universal mask- Mm-hmm. in our pre-clinical stage assets for HER2, PSMA, and EGFR. It's exactly the same mask, and so because you use it the first time around and you learn about it, it allows you to move faster in subsequent- You know, stages of development and going to next target, and then finally I would say that, you know, given that we have at Vir deep expertise in antibody engineering, there's a high synergy with the masking platform. So our ability to come up with, you know, really unique bispecifics, combined with that Pro-XTEN masking platform, will allow us to explore other potential targets for therapeutics going forward. Mm-hmm. You mentioned sort of the three programs, HER2, PSMA, and EGFR. Maybe if you could just touch on each in terms of where you are in development and kind of next steps for those programs? Sure. Yeah, so the first one, as I mentioned, it's a dual CD3 HER2, bispecific TCE. It is currently in phase I, dose escalation as a monotherapy and also in combination with pembrolizumab. So, you know, data is expected in the second half of next year. As I mentioned, if you think about, HER2-associated, unmet medical need. What we are targeting for this specific regimen is second and third line, metastatic breast cancer and third line metastatic, colorectal cancer. Again, and in those, for example, in third line, metastatic colorectal cancer, again, the five-year survival rate is around one in ten. So there's a high unmet need, and we hope that with this, T-cell engager program, we will be able to come up with an efficacious regimen that is also much safer, given the de-masking only in the tumor. So that's one program. It's the most advanced. It was the first program, and as I mentioned, what is very unique about the platform is that the same mask is being applied across the three programs. So for the HER2 program, the Sanofi, I mean, Sanofi team started from very low doses of drug, and they went into very small increments, increasing the dose, just, you know, to make sure that it was going to be safe. The second program, which is a dual CD3 PSMA T-cell engager, there the team was able to already start at a higher dose and move into larger dose intervals, because again, you were using the same kind of mask. So that second program is also in phase I dose escalation, and again, data is expected in the second half of next year. As I mentioned, again, in metastatic, castration-resistant prostate cancer, the five-year survival rate is around, you know, one in three, so still a high unmet medical need, and this is an opportunity to potentially address that. And then finally, the EGFR program, again, it's a dual CD3 EGFR. That is expected to go first in human in the first quarter of next year. So that, you know, has IND clearance and is moving towards the clinic. You mentioned the masking technology is kind of a universal mask, but in each program, is the efficiency of the unmasking in the tumor similar, or is it different based on different tumor types, or just, you know, how does that work? Yeah. So the linker has been designed such that there are eight different proteases that can cleave it, so it has really been optimized to be used in a tumor microenvironment. So it's the same type of linker, but it might be cleaved by different proteases, depending on, you know, the application. Makes sense. Maybe you can talk about just... You know, you recently announced the deal. I think there's, you know, a period where there's gonna be, like, a sort of a transition. Like, how's that going? When will you have everything in-house, or is this, you know, or is this pretty seamless? Yes. So we are still currently in the HSR period, so but closing is expected in the coming days. Post-closing, what will happen, of course, is, I think, a very swift transition, because as I mentioned, the people that have been associated with the program- Mm-hmm ... they are joining us. The people that have been associated with developing the platform are joining us, and the people that know how to manufacture it as well. So, you know, we hope to not really miss a beat in progressing these programs forward. And we have been, of course, you know, preparing very well for that transition. And you mentioned the potential also with the Pro-XTEN platform is to sort of develop some of your own programs and use that technology as well. How much of a priority is that? Is it more T-cell engagers? Is it more maybe monoclonals or different types of molecules, or how are you thinking about that? Yeah. So first of all, I want to reiterate that absolute priority is going to be on accelerating our hepatitis delta program. Yeah ... our hepatitis B program, and our other clinical stage, you know, assets, the three T-cell engagers. However, the platform holds tremendous potential, and so, you know, there is certainly thinking around, you know, how we could derive value out of the platform and come up with new therapeutics going forward. So post-deal closure, that, of course, will be a discussion with the team that we are bringing in. As I mentioned, in infectious disease, we have very strongly prioritized our preclinical programs, and we're really focused now on, you know, prophylaxis, RSV, and HIV cure. And for the T-cell engager platform, that will be a discussion post-close. Makes sense. How are you thinking about just business development going forward? Obviously, you still have a lot of cash, but you just had this deal. Are you kind of where you want to be, or are you thinking more sort of activity in the future? No, I think, you know, we have, again, post-close of this deal, built a very compelling clinical pipeline. The focus is really now on, as I mentioned, because we have phased out a number of programs that actually hold a lot of promise. For example, our preclinical influenza prophylaxis program, VIR-2981, as well as an ADC, are very, you know, promising molecules. It's not an area where we want to take the molecules forward, but the focus in business development is going to be on potentially finding partners for the phased-out programs. Yeah. Okay. Maybe we can shift gears, just the hepatitis delta and, you know, EASL. You shared some very promising sort of preliminary phase II data from your SOLSTICE study. Maybe just walk us through the key findings there. Sure. So yeah, first of all, just to remind everyone, hepatitis delta is the most severe form of viral hepatitis, and people who are co-infected with both hepatitis B and delta progress much faster to liver cancer, you know, need for transplantation and, you know, unfortunately also progress much faster to death. So what we have been showing at EASL were preliminary data from our SOLSTICE trial, 24-week treatment. And we saw some really, you know, compelling efficacy from our both monotherapy antibody tobevibart, as well as our dual regimen tobevibart plus an siRNA elebsiran. For the combination therapy, for example, after only 24-week treatment, we saw 55% of patients that had target not detected, which means that you can no longer detect the delta RNA virus in the blood of patients. This was very compelling data. We also showed that more than 50% of the patients achieved ALT normalization, which is important because it is, you know, a regulatory requirement to have a dual endpoint. We will have coming up at AASLD in November the full data set, you know, 24-week data on 30 participants with the combo regimen and 30 participants with the monotherapy. In the meantime, again, the data, even though preliminary on the combination, have been so compelling. We have achieved IND clearance, Fast Track designation on that combination. And clearly, you know, achieving such a high level of target not detected and significant levels of S antigen reduction has made us to choose for this combination regimen as a potential regimen, which we would proceed with into registrational studies. Can you maybe talk about what you saw in terms of cirrhotic patients and non-cirrhotic patients, and if there were any differences there? Yeah. So one of the questions that we received prior to EASL was, you know, will you be able to see the same level of efficacy in patients that have, you know, progressed to cirrhosis? And so even though it was still a small data set, 11 participants in the combination regimen, we saw absolutely no difference between cirrhotic and CPT-A cirrhotic patients. So that was actually a very promising outcome again, because, again, patients that have a dual infection of B and delta progress to cirrhosis very quickly. So it really opens up, you know, the perspective of the patients that you will be able to treat going forward. Yeah, and earlier in our conversation, you mentioned giving sort of an update on that study, I think, by year-end. Maybe just talk about, you know, what we should expect there. Is it just, you know, more patients, longer follow-up or? Yes. So we expect to share data in the fourth quarter, likely at, you know, AASLD in November, major hepatitis liver congress. So we will be sharing, as I mentioned, the full data set, 24 weeks, 30 participants on the monotherapy and 30 participants on the dual. We will have more data on, to your point, cirrhotic and non-cirrhotic patients. We will have safety data, tolerability data, so it will be a really informative data set on our SOLSTICE trial. And again, that will guide us in, you know, what our registrational trial is going to look like. We also have shared that we are planning interactions with regulators in the third quarter. Mm. So at that moment in time, we should also be in a position to share more information about our plans going forward. Can you talk just about the sort of market opportunity in hepatitis delta? You know, I think and also, you know, like how are patients identified right now and, you know, what percentage are sort of diagnosed? Yes. So certainly hepatitis delta is not... You know, it's, it's a very severe disease. It's a very high unmet medical need, yet unfortunately, diagnosis rates, especially in the United States, are really low, and we are looking into, you know, ways to change that going forward. The estimates, based on a lot of studies that have been done, is that there are approximately 100,000 delta patients in the U.S. and about 200,000 in Europe. So it, it resembles pretty much an, an orphan-like disease. The impetus for diagnosis, I think, will really come here in the United States when a regimen is available or there's an outlook of a regimen coming. Thus far, there's really no treatment available for patients in the U.S., so there's little incentive for physicians to even diagnose hepatitis delta. The situation is very different in Europe, so in Europe there is bulevirtide available on the market. There is reflex testing, meaning that if patients get tested for hepatitis B and they are positive, they get automatically tested for hepatitis delta, and we have seen some data that, for example, in Germany and in Spain, when that happens, the diagnosis rates- Mm ... for delta patients went up significantly, five- to sixfold, compared to just basing diagnosis based on risk factors. So that's very promising. And, you know, as these data, I think, evolve and come out, we are expecting that the guidelines in the United States will also change. Again, I think our initial data with our combination regimen is very compelling. And as that data gets, you know, reinforced, hopefully, you know, in November-... I think that there will be, again, if there's nothing out there to treat patients with, and there's no outlook of anything coming, there isn't really an incentive to diagnose. Mm-hmm. But I think if sort of there's, you know, potential treatments on the horizon, I think that might really change. And hepatitis delta, in that sense, is very similar to hepatitis C. It's also an RNA virus. It's very different from hepatitis B, where it's a DNA virus. You have the cccDNA, it's more complicated. But hepatitis delta is an RNA virus. And you know, again, what was seen in hepatitis C is that as soon as good treatments became available- Mm-hmm. More diagnosis happened, and, you know, over time, that really acted as a flywheel. So we are working, you know, with patient advocacy groups, policymakers. We are looking at, you know, ways to diagnose patients also for selection in our clinical trials. So we're doing a lot of effort, and I think, you know, the other players in the field are doing the same. So with, you know, again, the shift in Europe to reflex testing, the WHO putting guidelines out there for reflex testing, as that, you know, develops here in the United States, I think that will drive a lot of change. Yep. And you mentioned next step is sort of phase, the phase III study, and maybe just share, you know, your early thinking on what the trial design could look like, you know, in terms of duration, endpoints, et cetera. Yes. So we are working through now the design of our registrational study, which will be called ECLIPSE. And what we can say is that we will use bulevirtide as a comparator in that study. Because bulevirtide is the standard of care in Europe, it will be important for, again, reimbursement in Europe. It's going to be a study that we expect somewhere in patient size range between three hundred and five hundred participants in the study. So, you know, reasonable size, and again, we're gonna have interactions with the regulators to, you know, to agree and align on, you know, all the things that we have assumed to be true, and we will be sharing more about that- Yeah. -in November. Okay, great. May we just shift to hepatitis B, and maybe you can just talk a little bit about the phase II MARCH study. You shared some, some data already, I think, end treatment data at twenty-four weeks, and maybe just, you know, key... Tell us the key takeaways there. Sure. Yeah, so for hepatitis B, the aim is really to try and achieve a functional cure. So that's very different from what we have been discussing in hepatitis delta, where we're looking at chronic treatment. And what we have shown in prior data, to your point, Mike, is that after twenty-four weeks of treatment, with the combination of tobevibart and elebsiran alone or, with the addition of peginterferon alfa, we achieved about 15%, S antigen loss. And that was about a, you know, threefold increase compared to a combination of, elebsiran, the siRNA, and peginterferon alfa alone. So that was on itself already really promising. What we had seen before in hepatitis B in our, 1001 trial, was that moving from twenty-four-week treatment, elebsiran plus peginterferon, we had about 5% S antigen loss. To 48 weeks, we got to about 26% S antigen loss at the end of treatment. Then, you know, the functional cure rate is taking treatment away and look at what that looks like six months later. Mm-hmm. We achieved about a 16% functional cure rate. The data that we're gonna show in November in our MARCH Part B trial are the 48-week end of treatment data, and then the functional cure data will come in the second quarter of next year. Just as we think about the 48-week data, you know, in your view, what's kind of a good result on S antigen loss? And I guess, how high does it have to be, or is there a threshold you have in mind? I know you're gonna run the study out and kinda see where it ends up, but just, you know. Sure, yes. So we have had a lot of conversations with key opinion leaders and treating physicians around. You know, we have an opportunity for an interferon sparing and an- Mm-hmm ... interferon-containing regimen, and obviously we will have to see what the data tells us. However, what we have consistently heard is that physicians would like to see at least a 30% functional cure rate for an interferon-containing regimen, and they would, you know, be, you know, happy with a lower antigen, a lower functional cure rate for an interferon-sparing regimen. So if you take that into account, and you sort of understand that, between the 48-week end of treatment and the functional cure, you typically see a drop-off. Obviously, we would like to see, and it would be very promising, if we could see, you know, as antigen loss rates, you know, above 40% at least, you know- Mm-hmm. So that, you know, it tells you that you have a shot at achieving those kind of functional cure rates. So again, we will have the data on 50 participants in the doublet and 30 participants in the triplet are coming up in November. Mm. Is that at a medical meeting or is that- Yes, that will also be at AASLD. Okay. Mm-hmm. Got it. I think also you're planning a sort of an R&D day, I think, in November, if I recall. Maybe just talk a little bit about what you plan to share there? Yes, so R&D day will follow AASLD very closely. Okay. So we will use our R&D day to really talk through our hepatitis delta results, our hepatitis B results. You know, talk about the landscape, the opportunity, the paths going forward for hepatitis delta, especially, you know, potential future registrational trial design, et cetera. We will also use our R&D day to talk about, of course, our clinical stage T cell engagers and our thinking around that. And finally, you know, we will talk a little bit more about the two platforms that we have, the antibody engineering platform and the masking platform, and the synergies and some of our, you know, future thinking around potential applications around that. Mm-hmm. Okay. Maybe just last question, your current cash position, which, if I recall, is still pretty good, but maybe just remind us what that is and just, you know, with all these changes and looks like you have a very robust pipeline and you're advancing it quickly, like, what's sort of the... What does the runway look like? Yeah. So we shared that at the end of the second quarter, we had $1.43 billion in cash. As I mentioned at the beginning, we have very substantially reprioritized our pipeline, phased out programs, restructured the company. So that has freed up $90 million in cash savings, and it has also- Mm-hmm ... yielded about $50 million in cash avoidance for the course of next year. So and we continue to really look at how, you know, to get operationally more efficient. Mm-hmm. So we are just, you know, kicking off our budget cycle for next year. We have also shared that we are reducing our guidance for this year with $70 million. So we are taking a lot of measures to make sure that the cash that we have available is really going to be able to be deployed to accelerating our hepatitis programs and progressing the T cell engager programs, which is, of course, the core priority for the company. Okay, great. Looks like we're out of time, so, you know, we're looking forward to all these updates coming up, and Marianne, thanks so much. Appreciate your time today. Thank you, Mike. Appreciate it.