Vir Biotechnology, Inc.

Mooney Ellis, Executive Vice President, Chief Corporate Affairs Officer. You may begin, Mr. Mooney Ellis.

Thank you, and good afternoon. With me today are Dr. Marianne DeBacker, Chief Executive Officer, Dr. Phil Pang, Chief Medical Officer, and Sun Lee, Chief Financial Officer. Before we begin, I would like to remind everyone that some of the statements we are making today are forward-looking statements under the securities laws. These forward-looking statements involve substantial risks and uncertainties that could cause our clinical development programs, future results, performance, or achievements to differ significantly from those expressed or implied by such forward-looking statements. These risks and uncertainties and risks associated with our business are described in the company's reports filed with the Securities and Exchange Commission, including Forms 10-K, 10-Q, and 8-K. I will now turn the call over to our CEO, Dr. Marianne DeBacker.

Thank you, Sacha. Good afternoon and welcome. I'm Marianne DeBacker, CEO of VEER, and I'm pleased to welcome you all here today. Since the last time we spoke, VEER has made some impressive progress on driving our scientific platforms, our pipeline, and our clinical trials forward. All this positive momentum is encouraging as we seek to serve all the patients who are waiting, especially those with unmet medical needs in multiple infectious disease areas and beyond. Let me first call your attention to the updates we are most looking forward to at AESLD delivery meeting in Boston later this month. Our Phase II data readouts from two of our most advanced programs, Chronic Hepatitis B and chronic hepatitis delta. As a reminder, this includes initial data from Part B of the MARCH trial, where we are looking at combinations of our monoclonal antibody, PIER 3434, and our sIRNA, PIER 2218, for 24 and 48 weeks, with and without pachypnephrine alpha. We also look forward to sharing initial data from our ongoing solstice trial, which is evaluating whether our antibody, VR3434 alone, our siRNA, VR2218 alone, or the combination of these can be a viable chronic therapy for patients who are co-infected with hepatitis delta virus. Thanks to the approximately 50 million in new BARDA funding, we have had positive momentum on the development of VR7229. are investigational next-generation COVID-19 monoclonal antibodies with a distinct combination of potency, breath, and viral inescapability. This funding includes $40 million in Project NextGen non-diluted funding, which will support the development of VIRS7229 through Phase I. We expect the Phase I trial to initiate in 2024 and we will be exploring a partnership for the development of this antibody post-Phase 1. The BARDA funding also supports alternative monoclonal antibody delivery technologies, such as RNA-delivered monoclonal antibodies, which have the potential to revolutionize the field of antibody therapeutics with the ultimate benefit of enabling greater patient access and ease. This funding is another testament to VIIR's world-class antibody platform and our ability to discover rare, broad, and highly potent monoclonal antibodies with the hope of generating powerful new medicines. Switching gears to one of our newest clinical programs, in September, the first participant was dosed in a Phase I trial evaluating VIIR 1388. an investigational novel T-cell vaccine for the prevention of HIV. This trial is especially meaningful because it brings us and our supporters, which includes the Bill and Melinda Gates Foundation, the National Institute of Allergy and Infectious Diseases, and the HIV Vaccine Trials Network one step closer in our shared pursuit of developing an HIV vaccine. We are hopeful that our unique approach will help close the longstanding public health gap in HIV prevention, and we look forward to sharing initial data from this trial in the second half of 2024. Finally, I want to give you a glimpse into some of the transformative strategic decisions VEER has made to drive future growth and increase patient impact. As you know, our founding mission was a world without infectious disease. And we are now embarking on a broader vision, powering the immune system to transform lives. We have always seen ourselves as an immunology company first and are now ready to expand into new areas of growth by applying our deep immunology expertise beyond infectious disease with the first applications in autoimmune diseases and immuno-oncology. This is made possible by our platform that has already created monoclonal antibodies with enhanced selectivity and potency using AI-based protein engineering. We have existing in-house immuno-oncology experience, and we are already advancing enhanced antibodies for tumor immunotherapy with augmented selectivity and potency under the leadership of Dr. Alan Korman. Senior Vice President of Immune Targeting here at VIIR. Prior to joining VIIR, Alan led the discovery of three approved drugs for oncology. We are also embarking on a novel, agnostic way to identify T-cell receptors specific for tumor antigens, an effort led by our National Academy of Sciences Immunologist, Dr. Antonio Lanzavecchia. We look forward to keeping you updated on this in 2024. We believe all of this is within reach thanks to our strong balance sheet, which allows us to take our chronic hepatitis B and chronic hepatitis Delta programs through development inflection points, as well as invest in our core antibody platform and evaluate complementary external opportunities. Meanwhile, we will continue to be judicious in our spend and investments to ensure that we maximize the deployment of the $1.7 billion in cash and investments. Finally, I want to highlight that next week we will be welcoming our new Chief Scientific Officer, Dr. Jennifer Towne. Jennifer brings more than two decades of R&D experience and a proven track record of successfully developing breakthrough medicines and bringing multiple investigational new drug applications for innovative therapeutics forward. This includes bringing 16 drug candidates from preclinical research to IND and early clinical development. Her scientific and external innovation leadership experience, combined with her deep immunology expertise, will be critical to delivering on our strategy to go beyond infectious disease. I want to thank Phil Pang for expanding his responsibilities as interim head of research. Phil will continue to lead clinical research, development, and medical affairs as chief medical officer to bring our late-stage portfolio to fruition, which is our top priority at VIIRS. With that, I'll now turn the call over to Phil to provide an update on the progress we are making in our preclinical and clinical programs.

Thank you, Mary Ann. As Mary Ann mentioned, we are looking forward to sharing at ASLD data from our Phase 2 March chronic hepatitis B trial and our Phase 2 Solstice chronic hepatitis delta trial. First, I want to talk about chronic hepatitis B and our goal, which is to achieve a functional cure defined as lifelong control of the virus after a finite duration of treatment, a goal that would be welcomed by the 300 million people living with chronic hepatitis B. The only treatment available to achieve a functional cure is arduous and results in a functional cure only 3% to 7% of the time. We are aiming to set the bar much higher with a goal of achieving a 30% or better functional cure rate. Our hypothesis is that you cannot achieve a functional cure with only an antiviral or only with an immunomodulator, but you really need both mechanisms of action, which is exactly what we are evaluating in our multiple ongoing clinical trials. Our vaccinal antibody, VIR3434, and our siRNA, VIR2218, can potentially act as both immunomodulators and antivirals. VIR3434 has three mechanisms of action. First, it is a neutralizing antibody, preventing viral entry of HPV and HDV virions. Second, via enhanced obstinization, it removes viral particles and subviral particles from the bloodstream. Third, it has a modified FC domain, which allows it to act as a potential direct immune activator, capable in vitro of stimulating dendritic cells to mature and create T cells against HPV or HPV. This is otherwise known as a vaccinal effect. VIR-2218 can act as an antiviral by knocking down HPV RNA transcripts. Vir-2218 can also act as a potential immunomodulator because we believe the HPV protein, hepatitis B surface antigen, is an immune tolerogen. And by knocking it down, we can unleash the brake on the immune system. So Vir-2218 is designed to act, by analogy, like a checkpoint inhibitor. We have demonstrated that when Vir-2218 plus PEG interferon alpha is given for 48 weeks, about 30% of participants achieved hepatitis B surface antigen loss at the end of treatment and about 16% had sustained hepatitis B surface antigen loss 24 weeks after the end of treatment. Although the number of participants treated to date is relatively small, this is the first demonstration that siRNAs can have a potential impact on functional cure rates. In that same study, we identified that we may be able to predict who will have an off-treatment response based on their endogenous anti-HPS antibody levels at the end of treatment. Veer was also the first to demonstrate the additive impact of combining an siRNA and a monoclonal antibody, specifically Veer2218 with Veer3434. This combination resulted in the largest declines in hepatitis B surface antigen ever observed after just 12 weeks of combination therapy. In part B of the March study, we are evaluating Veer2218 plus Veer3434 with and without PEG interferon alpha for 24 and 48 weeks. To remind you, after 24 weeks of VR2218 plus PEG interferon alpha without VR3434, we saw that 6% of patients achieved hepatitis B surface antigen loss at the end of treatment. Thus, for AASLD, the fundamental questions are around the role of our vaccinal antibody, VR3434. First, if we add VR3434 to VR2218 plus PEG interferon alpha, will we see an end of treatment response greater than 6%? Second, if we replace PEG interferon alpha with VR3434, will we see an end of treatment response better than 6%? Third, if we give VR3434 for 24 weeks or more, will we see any signs of immunomodulatory activity suggestive of a vaccinal effect? If so, that would strongly support the potential role of VR3434 in a functional curative regimen. Now, let's shift fears to chronic hepatitis delta. About 100,000 people in the United States and potentially over 200,000 in the EU5 are currently estimated to have HPV-HDV co-infection. This is likely to be an underestimate given the underdiagnosis rates for chronic hepatitis delta. We believe having a highly efficacious, easy-to-use treatment for chronic hepatitis delta will drive the desire to be diagnosed. Delta is one of the most severe forms of viral hepatitis with four times greater risk of liver cancer and two times greater risk of death compared to hepatitis B. Notably, we don't yet have potent chronic viral suppressive therapy for Delta. In recognition of this urgent unmet medical need, there are potentially accelerated paths to approval. Our antibody, Vir3434, and our siRNA, Vir2218, can also inhibit the hepatitis Delta life cycle because hepatitis delta virus requires the hepatitis B surface antigen to be infectious. Notably, with the only currently available chronic treatment, 12% of patients achieve undetectable HDV RNA after a full 48 weeks of therapy, with 45% of patients receiving some benefit. This regimen also requires lifelong daily subcutaneous injections. We have challenged ourselves to develop a chronic suppressive therapy that is better, not just in terms of efficacy, but also in terms of convenience, safety, and tolerability. I'm excited to see if we can get there. Data from the SOLSTICE trial will be shared as a late-breaker oral presentation at AASLD. Specifically, we will be evaluating the safety and antiviral efficacy of VIIR 3434 alone, VIIR 2218 alone, and the combination of the two together in a small cohort of participants. Looking ahead to what we believe will enter the clinic next is VIIR 7229, our next-generation investigational COVID-19 monoclonal antibody, which is being funded in part by BARDA. This funding includes the parallel research and development of next-generation RNAs, such as circular RNA or self-amplifying RNA, that would actually encode this antibody, potentially allowing your own cells to make VIIR 7229. This would be the ultimate combination of RNA and antibody technology. Instead of using RNA to encode a protein that your body then must develop an immune response against, this is about RNA encoding an antibody that directly defends you. Finally, a quick look back. As I know there remain questions about VR2482, our investigational prophylactic influenza A antibody. Our ongoing post hoc analyses have yielded the following two important insights. First, VR2482's ability to reduce cases of symptomatic flu improves to 57% for the 1,200-milligram dose when the case definition includes fever. That is how symptomatic illness is defined. Second, this relative risk reduction increases further to 65% when excluding the cases of flu that occurred within a few days of dosing. Notably, our next-generation antibody, VIR2981, is not only more potent in vivo, but covers both flu A and flu B. Furthermore, because it inhibits the neuraminidase enzyme, like all current flu antivirals, its mechanism of action has been clinically validated and is de-risked. The IND submission for VIIR 2981 is anticipated in the second half of 2024. In addition to VIIR 2981 and VIIR 7229, we have two other preclinical candidates that we expect an IND filing for in the next 12 to 24 months. Vir8190 is an investigational monoclonal antibody against respiratory syncytial virus and human metapneumovirus. You may have heard the news of the incredible demand surrounding the currently available MAP for RSV. Imagine if you could have a single monoclonal antibody that not only covers RSV, but also a second virus, human metapneumovirus, that also causes significant morbidity and mortality in infants. We also have an investigational novel therapeutic vaccine candidate for control of high-grade squamous epithelial precancerous lesions and HPV cancers that is called VIIR 1949. Our talented researchers here at VIIR have been very busy executing, and I'm excited to hand over the reign to Jennifer Towne as Chief Scientific Officer. She will no doubt further bolster our innovation mindset. I will now turn the call over to Chief Financial Officer Sung Lee.

Thank you, Bill. We're pleased to share our financial results for the third quarter of 2023. Total revenues were $2.6 million compared to $374.6 million for the same period a year ago. The primary reason for the decline is lower collaboration revenues from Citroën MAP compared to a year ago. We continue to expect collaboration revenues to be at minimal levels and potentially make a negative contribution to our top line due to the ongoing required investments to support the marketing authorization of Citrovimeb, which our partner GSK leased the efforts in. Turning to operating expenses, R&D expenses in the third quarter of 2023 were $148.3 million compared to $114.2 million in the same period in 2022. In the third quarter of 2023, we record an expense of $21.9 million for the cancellation of Phase III manufacturing activities for VIIRD-2482, our investigational flu monoclonal antibody. With this expense recorded, costs related to VIIRD-2482 are now largely behind us. Other drivers of year-over-year growth were the investments in our ongoing Phase II studies in hepatitis B and hepatitis delta. SG&A expenses in the third quarter of 2023 were $41.1 million compared to $43.2 million for the same period in 2022. The decline was primarily driven by lower consulting expenses and stock-based compensation. For the third quarter of 2023, we reported a consolidated net loss of $163.4 million compared to a net income same period in 2022. Turning to the balance sheet, we ended the third quarter of 2023 with cash and investments of $1.74 billion compared to $1.9 billion at the end of the second quarter of 2023. During the third quarter, we made a payment of $67 million to our collaborator GSK for excess Petrobimab supply and manufacturing capacity which were originally recorded as a liability in 2022. With this recent payment, the liability to GSK is effectively paid off. Excluding the payment to GSK, our cash utilization during the third quarter was approximately $94 million. In closing, I would like to add that we are taking measures to optimize our cost structure I will now turn the call back to Sasha.

Thank you, Sung. We will now start the Q&A section. Please limit questions to two per person so that we are able to get to all of our covering analysts. Operator, please open up the lines.

Our first question will come from the line of Gina Wang with Barclays. Please go ahead.

Thank you for taking my questions. I have two questions. One is a big picture question for Marianne. So you mentioned that you wanted to expand strategic focus on autoimmune diseases and immuno-oncology. Could you share with us your key rationale for selecting the lead indications? And my second question is more for Phil regarding the AASOD update. And if I hear you correctly, you mentioned that you're looking for, in general, for HPV over 30% functional cure. So for this particular March Part B data, you know, giving we know that this is still on treatment, completed treatment. So what will be the initial bar you will be looking for so that we can maintain, say, after six months of treatment that could be above 30%?

Thank you very much, Gina. Appreciate those questions. Maybe first on the big picture one, as you mentioned. So as you know, our ambition here at Veer is to become an integrated commercial company. And of course, with products that address significant unmet patient need. And ever since Veer was founded, we have first seen ourselves as an immunology company. So what we have been doing at Veer is always, you know, aiming to bolster the immune system's ability to fight disease. And in the first seven years, clearly, that was focused entirely only on addressing unmet need in infectious disease. However, as you well know, we have both a very powerful B-cell antibody platform, and we have a T-cell platform. And we really want to build on those tools to make an impact in a much broader area. We can use exactly the same type of technologies and platforms to also, for example, help tip the balance of the immune system to fight cancer or to address, you know, diseases where the immune system really has gone awry, such as in autoimmune disease. And we are not starting here from scratch. We already had a small team focused on immune targeting and oncology under the leadership of Alan Corman. who, as mentioned in my introductory comments, is the person who discovered three blockbusters, really, in immuno-oncology, some of those being Yervoy and Urivo while he was at BMS. And as also mentioned in my prepared comments, we also have here a world-renowned immunologist, Antonio Lanzavecchia, who is really working, again, on a novel agnostic way to identify T-cell receptors specific to very specific tumor antigens. So we have a lot here to build on, and mostly we want to make sure that all that great knowledge and platform technology that we have, also using AI and machine learning, for example, to enhance the interaction of antibodies with cells of the immune system, that we do not just limit ourselves to exploring that in infectious disease. but also explored in other areas where there's significant unmet patient need. Now turning to your second question as to the AASLD updates, I would just maybe start with reminding everyone where we come from, and then I will invite Phil to provide a little bit more color on what we will be reading out at AASLD. So just for everyone to remind ourselves. In hepatitis B, we started by testing the hypothesis whether combining an antiviral and an immunomodulator would be able to exert a significant effect in chronic hepatitis B patients. And we started off initially by looking at if we would add to interferon alpha where functional cure rates after 48 weeks of treatment were only 3% to 7%. if you would add to interferon-alpha RSI RNA, could you actually increase that functional cure rate? And as Phil mentioned in his prepared comments, I mean, we have thus far shown a 16% sustained as antigen loss with that combination, and that's really the highest antigen loss that has thus far been reported for a regimen in this field. We then want to go on and answer the question, could we potentially replace interferon-alpha with our antibody 3434, or what would it look like if we would replace, or what would it look like if we added 3434, our antibody, to that regimen? So in March Part A, we started answering that initial question. Again, only with short treatments, 5 and 12 weeks in Part A of the March trial, we could see that combining an siRNA and our antibody is really delivering additive effects. We achieved 2.7 log decline in S antigen, and there were no safety signals seen to date. So that gave us a lot of confidence to look forward to our Part B results where we actually are exploring the same combination with and without back interferon, but now for longer treatment durations, 24 and 48 weeks. And perhaps with that intro, I want to ask Phil to provide a little bit more color what is there to expect at AASOD.

Thank you, Marianne. And thank you, Gina, for the question. So, maybe I'll put a couple of statements in context first, which is that, you know, predicting off-treatment rates from on-treatment response rates is still very much in its infancy. As you know from our previous presentation at EASL, we were the first to demonstrate that if you had an endogenous anti-HBS response, you were more likely to have an off-treatment response. And that was one of the first times there was any hint of a predictor of off-treatment response from on-treatment response. So I can just say generally that, of course, in answer to your question, if one is looking for a greater than 30% off-treatment response, then the on-treatment response should be at there or higher. And that would be the clinical bar to progress a regimen forward. And that's true for all the regimens that we're looking at. But to be specific at ASLD, I think what's really important to think about is that with Mary Ann's statement, we've proven that 2218 can have a role in a functional cure. The next question is, can 3434 have a role in a functional cure? And that's why in my prepared remarks, I talked about the fact that when you have 2218 plus interferon for 24 weeks, you see only 6% of patients having an end of treatment response. And the first question we need to answer is, if we add 3434 or replace PEG interferon, will we move beyond that? And therefore, really honing in on the role of 3434 that it can have either in achieving an end-of-treatment response and then hopefully later on an off-treatment response. So the answer to your question is that predicting an off-treatment response from an on-treatment response is still in its infancy. You would need at least a 30% rate. And what we're focused on for ASLD is will 34-34 get us closer to that answer?

Our next question will come from the line of Paul Choi with Goldman Sachs. Please go ahead.

Hi. Thank you, and good afternoon, everyone. I want to maybe follow up on Gina's question regarding the expansion into autoimmune and immuno-oncology. Marianne, could you maybe sketch for us, you know, how you're thinking about the metrics that you're going to share with the street in terms of how to further allocate capital and just sort of, again, how the street might be able to keep score on your progress and expansion into these two areas. And then second, regarding RSV, I was wondering, I realize it's still a relatively early stage, but given the commercial success that Pfizer and Sanofi are seeing with their products, can you maybe, again, sketch out how you envision clinical development of 8190 over the next couple of years? Thank you.

Thank you, Paul. Maybe we'll start with the RSV question. Phil, do you want to give a bit more color on where we stand with the program?

Yes, definitely, Paul. So thank you for that question. So with our 8190 antibody, which is both covering both RSV and human metapneumovirus, the answer is that we believe we can bring an IND forward in the next 12 to 24 months. And the path is relatively straightforward and has really been blazed by others. Where in the infant population, what you're trying to demonstrate is prevention of lower or lower respiratory tract infection, medically attended respiratory tract infection or lower respiratory tract infection. And we believe that there's a relatively straightforward path to do so after you obtain phase 1 PK data. Beyond that, as you know, this is a partnered program with GSK. And we are working closely with our collaborator to determine the fastest and most robust path forward. So that's what I can say about the 8190 at this time.

Thank you, Phil. And then, Paul, on your first question, I first want to clarify that the efforts we are doing in these new areas are at discovery stage. And maybe also start to provide a little bit more background on how we are allocating capital here.

Yeah, thanks, Marianne, and thanks, Paul, for the question. So, Paul, in terms of the metrics, as Marianne said, the efforts in autoimmune and oncology would be discovery, and that's not an expensive part or doesn't require a large investment at VEER. The capital allocation here will still largely be directed to our mid-stage programs in hepatitis B and hepatitis delta. Those will be ongoing. for the foreseeable future, and the majority of our capital allocation will be directed there. Now, I just want to add something here. We have, in the past year to date, our capital allocation has been heavily directed towards a couple of items. Obviously, the phase two flu study and the related phase three manufacturing activities. Also, the liability we have to GSK

Yes, and I would just add, in addition to capital allocation to predominantly our clinical stage programs, of course, we continue to explore if there are external innovation opportunities that could help us accelerate our programs or complement what we are doing here. Thank you, Paul.

Your next question comes from the line of Eric Joseph with JP Morgan. Please go ahead.

Hi there. It's Billy on for Eric. A couple of ones from us. First, just following up from that last question. So with the external opportunities, do you see this as something maybe for more the new immuno-oncology side or the historical virology side of the business? And then I'll follow up my own after.

I'm very sorry, Eric. We could not understand you very well.

Hi, sorry. Can you hear me now?

Would you try again?

Yeah, so the question was just following on from the previous question about the, you said some complementary external opportunities you were looking at potentially, and whether these would be more in the immuno-oncology space or in the historical space of virology.

Okay, thank you for that question, Eric. Yes, so as mentioned, we are looking at external innovation really from the perspective of How can we accelerate what we are already doing? I really do believe that we have world-class expertise in our platforms, and we want to, of course, stay at the forefront in our field. And so we are looking at anything that could help us stay there and potentially leapfrog. So that can, you know, both be in infectious diseases or beyond.

Okay, thanks. And just one quick one about the HPV program. Looking forward to the off-treatment follow-up data you've now guided to in 2Q24. Would you expect patients to be able to be off the nuke by that point or still on nukes? Thanks.

Thank you for the question. This is Sopeng. So 24 weeks post-treatment, they will... It's actually somewhat of a mixed bag, but you can continue to expect that they will still be on nukes, and usually what happens is once they've demonstrated that they have lost surface antigen for at least six months off treatment, their nuke is stopped, and then you follow them for another period of time to make sure that they don't relapse further. I will say, though, that as you know, the nukes usually only suppress HBV DNA, and therefore surface antigen loss, which is a protein, would be unexpected to be impacted by the nucleoside reverse transcriptase inhibitor. So although, of course, it's not a perfect match, I think that what we're looking forward to and what we're guiding to is the post-treatment data off our drugs but still on the nucleoside reverse transcriptase inhibitor.

Great. Thank you. Thanks very much. Thanks, Bill.

Thanks, Derek. Your next question comes from the line of Patrick Truccio with HC Wainwright. Please go ahead.

Thanks. Good afternoon. First, I'm wondering if you can discuss the bar for regulatory approval in HDV or hepatitis delta and what you would need to see in SOLSTIS to give confidence that this program is on track. And secondly, what would be the next steps for the delta program? Specifically, you know, would you possibly be able to move directly into a phase three program after a SOLSTIS readout based on all of the data that's been generated across HBV and HDV?

Yeah, thank you for that question. So, I mean, as you know, the goal of therapy in Delta is chronic viral suppression as well as reduction of liver inflammation. That's also how the bar is set on the regulatory side. Phil, do you want to add any more color to what we want to see in solstice?

Yeah, definitely, Marianne. So, exactly as Marianne said, the regulatory bar is too long decline in HDV RNA and normalization of ALT. That was one of the bars that was set early on to allow for and incentivize drug development. And I think that that's one of the bars one can look at. But I think another bar to look at is undetectability and HDV RNA. That is another marker that is tightly associated with clinical benefit. So we're looking at both of those bars. I do want to remind you that for AASLD, we're going to be having a small cohort of patients treated for a relatively short period of time. And I think that we'll have to just wait to see what that data looks like to be able to know what the next steps are going to be. But as I've mentioned in my prepared remarks, the regulatory pathway can be accelerated if warranted, given the unmet need in this space.

Yep, that's helpful. Thank you very much.

Thank you, Beth. Your next question comes from the line of Rowana Ruiz with Learing Partners. Please go ahead.

Hi, good afternoon. This is Nick Gassick on for Rwana. Thanks for taking our questions. Maybe first, could you remind us, I guess, what the status is of the next generation 2981 antibody against flu A and B? I guess, could you talk a little bit about how this antibody is differentiated from 2482, aside from the flu B targeting aspect as well? And then secondly, could you discuss some of the learnings which you might apply from your experience developing 2482 in flu A to the development of 2981 in flu A and B. Thanks.

Yes, thank you for that question, Nick. Yeah, so I will start and then ask Phil to provide a little bit more depth. So first of all, as you rightly pointed out, one of the major differences between 2482 and 2981, our next-generation flu antibody, is the fact that it covers both flu A and flu B. It's also a different mechanism of action. It's an arminidase inhibitor, and that is, you know, a mechanism of action that has been proven to work before. We have also seen in vitro that the antibody is more potent than 2482. So there's a lot of differentiating components here for our next-generation antibody. that we feel are very relevant and interesting. And as it relates to our learnings from 2482, as Phil pointed out in his prepared remarks, there's some learnings that we already have based on initial data analysis. I mean, obviously, we have seen that for the clinical trials, it does make a difference whether you include fever in your primary endpoint. It also is really important how much time elapses between someone being dosed and someone being infected. So these are, of course, very important learnings for us. And we are, of course, continuing to analyze the data and grasp as much learnings as we can for our next steps. And maybe, Phil, you can talk a little bit more about all the data analysis that is ongoing and that we're planning to learn more about by beginning of next year.

Definitely, Marianne. So, Nick, one of the critical questions that always exists, regardless of the space, and especially is true for infectious disease, is how does your in vitro or in vivo results translate into the clinic? And so one of the critical questions, in addition to all the lessons that Marianne pointed out, is how do we calibrate dose between in vivo findings and clinical efficacy? So one of the advantages of having really been the first company to ever run a prophylactic outpatient flu trial is we now will and soon will have the data that really calibrates PK to PD, as I mentioned in my, as I may have mentioned previously, which allows us to really understand the dose and concentration that is necessary and translate in vitro and in vivo findings to people. And so that will be a very useful part of our 2981 development, in addition to what Marianne mentioned about clinical endpoints and timing is really trying to calibrate that, bridge that gap and using 2482 to help inform 2981. And we're already planning a series of studies to make sure that that gap is as small as possible.

Oh, well, thanks. So thinking about this future trial design, would you consider using the WHO and CDC endpoint as your primary, I guess, future trials in flu? How should we think about that? Since they both feature fever.

Yeah, so I think we may be even a little bit more advanced beyond that. We are basically certainly recognizing that fever is an important, or temperature if you would. Now they do have a slightly different temperature between the CDC and the WHO, 37.8 versus 38.0 degrees Celsius. So we are looking into that as well as any other symptoms that are well covered by 2482 in post hoc analyses. So we're going to put all that together to decide. But certainly, fever will be a part of what we consider moving forward.

Thank you, Nick. Your next question will come from the line of Eva Previtero with TD Cowan. Please go ahead.

Hi, good afternoon, and thanks for taking our questions. We have one on the solstice trial with data at AASLD. approximately how many patients' worth of data should we expect, and are each treatment group pretty balanced, and what efficacy measures do you expect to report in addition to the primary endpoint?

Thank you, Eva. I will just say that obviously this will be the very first time that we show really very initial data also from our folks' trial. So as Phil mentioned in his prepared remarks, this is still with a small number of participants in each of the arms, but we will see some initial data on, of course, 2218 alone, 3434 alone, and then the combination. Anything to add there, Phil?

No, I don't think I... Maybe I'll just clarify a couple of things that Essentially, we are going to be looking at, as Marianne pointed out, the monotherapy and the combination therapy. And the way in which the study is designed is we enrolled a very small number of patients in those monotherapy arms. And then if they showed signs of antiviral activity or didn't show signs of antiviral activity, they would or would not roll into a combination treatment arm to be able to really understand how the two drugs work together or don't work together. So that's going to be the design of the trial, and we look forward to sharing data at ASLD.

Thank you. How important is getting HTV to undetectable levels, granted that the regulatory bar is the two log decline?

So I think that the answer to your question is certainly getting to undetectable is a higher bar than a two log decline. I think that there is good clinical data suggesting that undetectability correlates well with clinical outcomes. And I think that, as I mentioned before, you know, with the current therapy, it's about 12%. So I would say that that 12%, of course, happens after a full four weeks of therapy. And the question is, can we meet or do better than that, given the fact that we have been following our patients for a much shorter period of time? So I think we'll just have to wait and see what ASLD has to say and let the science speak.

Thank you very much. Thank you, Ethel. Your next question comes from the line of Joseph Stringer with Niedermann Company. Please go ahead.

Hi, thanks for taking our question. Just a quick one on the HIV program, the phase one readout. What type of data do you plan to announce from that the second half of next year, and what would give you confidence, or what would you need to see to proceed the next steps in that program?

Yes, thank you for that question, Joey. Joe, do you want to take that one? Thank you.

Definitely. So, as you noted, Joey, it is a phase one study. It is an immunogenicity study in healthy volunteers. So, the primary endpoint is obviously safety plus immunogenicity. And so, the answer is we expect to have an understanding of, one, is the insert, which is obviously for CD8 T cell responses, or sorry, rather CD8 T cell responses against the cassette. Then the next question is, if we do, what type of T cells are we creating? Are we creating what we're calling effector memory T cells, which are really T cells that are very special, that reside in the mucosa, they're ready to fight, they don't need to multiply before they can have impact. And then third, if possible, to understand what type of HLA restriction they have and whether or not, for example, they will be restricted by MHCE, which is something that will be a very unique immune response, which might be harder for the virus to overcome. So all those are things we are looking for in our immunologic readouts. We are planning initial data from those immunologic readouts next year.

Right. And then maybe just to add that, you know, the HCNB-based vaccine, or what we call the T-cell platform, I mean, learning Those initial data for HIV will also really be helpful in guiding us for our next investigational T cell vaccine that is focused on HPV.

Thank you for taking our question.

Thank you, Joy. And I'll now turn the conference back over to Dr. Marianne DeBacker for closing remarks.

Okay, thank you, operator, and thank you all again for your time and attention today. To close, I just want to leave you with these couple of takeaways. First, we continue to make progress on our clinical programs, and you can expect new data from our ongoing Phase II chronic hepatitis B and chronic hepatitis Delta clinical trials to be presented on November 13th. Second, we are expanding our strategic focus beyond infectious disease, first to autoimmune diseases and immuno-oncology. We are also pioneering the discovery of RNA-delivered monoclonal antibodies, thanks to the help and new funding from BARDA. And lastly, the $1.7 billion in cash and investments that we have available supports the advancement of our hepatitis B and Delta clinical trials, and our core antibody platform, yet additionally, it enables us to evaluate complementary external opportunities that strengthen our existing platforms and pipelines. So, thank you again, all of you, for joining us today. We really appreciate your time and your interest in VIEW. Operator, you may hand the call.

Thank you all for joining. This does conclude today's meeting. You may now disconnect.