Hello. Welcome to Vir Biotechnology’s Second Quarter 2024 Financial Results and Business Update Call. As a reminder, this conference call is being recorded. At this time, all participants are in a listen-only mode. After the speakers' presentation, there will be a question-and-answer session. [Operator Instructions] I will now turn the call over to Richard Lepke, Senior Director of Investor Relations. You may begin Mr. Lepke.

Thank you, operator and hello everyone. I am Richard Lepke, Senior Director of Investor Relations at Vir Biotechnology. Joining me on the call are Dr. Marianne De Backer, our Chief Executive Officer; Dr. Jennifer Towne, our Chief Scientific Officer; Dr. Mark Eisner, our Chief Medical Officer; and Brent Sabatini, our Chief Accounting Officer. Before we begin, I would like to remind everyone that some of the statements we are making today are forward-looking statements under applicable 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 today's press releases and the company's reports filed with the Securities and Exchange Commission, including Forms 10-K, 10-Q and 8-K. With that, I will turn the call over to Marianne. Please go ahead.

Good afternoon, everyone, and thank you for joining us today. At Vir, our mission is powering the immune system to transform lives. During today's earnings call, we will discuss two significant announcements that mark critical milestones on our journey to realize this vision. Before we dive into these announcements, let me quickly highlight some key achievements from the second quarter. We presented promising Phase 2 SOLSTICE data in chronic hepatitis delta at the EASL Congress, which generated significant interest from both scientific as well as the medical community. These preliminary data underscore the potential of our combination therapy to tobevibart and elebsiran to revolutionize the treatment landscape for people living with hepatitis delta. We are now preparing to engage with regulatory authorities to discuss the registrational path forward. We also recently received FDA IND clearance and fast track designation for this combination therapy. In parallel, we remain focused on advancing our functional cure program for chronic hepatitis B, and we eagerly anticipate reporting 48-week end of treatment data from the Phase 2 MARCH Part B study at the major medical congress in the fourth quarter. Now let me turn to the two significant announcements that will be the main focus of today's call. First, I'm excited to announce that Vir has entered into an exclusive worldwide license agreement with Sanofi for three clinical-stage masked T-cell engagers and the exclusive use of the PRO-XTEN protease-cleavable masking platform for oncology and infectious diseases. This license agreement is subject to HSR review and clearance, which we expect will take about 30 days from signing. Second, we will be providing a corporate update on our strategic restructuring. To provide you with a comprehensive overview of these announcements and their impact on our company, we have structured today's call as follows. First, I will summarize…

Thank you, Marianne, and hello, everyone. As you can see on the slide, the PRO-XTEN technology consists of a protease releasable XTEN mask that can be universally applied to various protein therapeutic modalities. The PRO-XTEN technology has two key features. First, it implies the universal mask, which in the case of a T-cell engager is applied to both arms, masking both the part of molecule that targets the tumor-associated antigen and the part that activates the T-cell, the CD3 arm. Second, the technology utilizes a protease-cleavable linker, which enables preferential and masking and drug activation, specifically in the tumor microenvironment. This is possible because the tumor microenvironment is known to have high levels of specific proteases that concludes the linker, releasing the active drug from the XTEN mask. The PRO-XTEN technology can be applied to T-cell engagers, cytokines and likely other modalities. This masking technology allows for the selective activation of potent immune modulators at the site of the tumor, while minimizing their activity in healthy tissues. The XTEN mask has been clinically proven with ALTUVIIIO, an approved drug to provide half-life extension to the mask molecule. Now let's take a closer look at how this technology can overcome the historical limitation of T-cell engagers and unlock new opportunities in cancer treatment. In blood circulation, the molecule remains fully masked with all of its components, including the XTEN mask, the linker and the tumor targeting and T-cell engaging components, all intact and connected. This mask configuration allows for a long half-life in the blood, which is essential for effective drug delivery to the tumor site. As the masked T-cell engager reaches healthy tissue, the dual masking of both the tumor-associated antigen and the CD3 arms limit binding to healthy cells and T-cells. This unique feature reduces T-cell mediated cytotoxicity, thereby…

Thank you, Jen, and hello, everyone. I'll now provide an overview of these programs and our plans for clinical development. Following closing, the licensing agreement would provide us with a robust portfolio of assets targeting clinically validated antigens in oncology. These assets include three dual masked T-cell engagers each targeting a different antigen HER2, PSMA and EGFR. 6309 is a dual masked HER2 CD3 T-cell engager. This asset has the potential to address significant unmet needs in HER2-expressing cancers with initial indications, including third line or later HER2-positive metastatic colorectal cancer and second to third line HER2-positive metastatic breast cancer. 6329 is a dual masked PSMA CD3 T-cell engager. This asset is initially being developed for the treatment of third line or later metastatic castration-resistant prostate cancer, the disease with limited treatment options and poor outcomes. 6368 is a dual masked EGFR CD3 T-cell engager. This outset has the potential to address multiple EGFR-expressing tumors with initial indications, including third line or later metastatic colorectal cancer, second to third line metastatic non-small cell lung cancer and second to third line metastatic head and neck carcinoma. While we refer to specific lines of therapy and initial indications for these assets, it's important to note that our goal is ultimately to move up to earlier lines over time as the data support. HER2, PSMA and EGFR are all known to be important targets in a variety of solid tumors and existing therapies against these targets have demonstrated clinical benefit. However, existing therapies often come with significant toxicities, which can limit their ability to be dosed high enough to achieve optimal efficacy. In the following slides, I will provide more details on each of these assets, including their current clinical development plans. Now let's dive deeper into 6309, the dual masked HER2 CD3…

Thank you, Mark. I would now like to discuss the financial aspects of this transaction and how it aligns with our strategic priorities. Following closing, our license agreement with Sanofi will provide us with exclusive rights to three clinical-stage dual masked T-cell engagers. In addition to these clinical-stage assets, the agreement will also provide us with exclusive use of Sanofi's protease cleavable masking platform for oncology and infectious diseases. After HSR clearance, which we expect will take about 30 days from deal signing, Vir will be responsible for and have sole decision-making authority over all development and commercialization activities related to these assets. In exchange for these rights, Sanofi will be eligible for future development, regulatory and commercial net sales-based milestone payments as well as tiered royalties on worldwide net sales. These payments are structured to allow Sanofi to benefit from Vir's successful advancement and commercialization of these assets. As part of the agreement, at closing, we will make an upfront payment of $100 million as well as a near-term escrow milestone payment of $75 million, which is subject to 6368, achieving first-in-human dosing totaling $175 million in near-term payments. As we anticipate integrating the newly licensed assets into our pipeline, we are also taking steps to prioritize our R&D portfolio and restructure our workforce to ensure that we are allocating our resources to the opportunities with the highest potential for patient impact. By concentrating our efforts on our key programs, we believe we can maximize value creation. As part of this prioritization, we have made the decision to stop our R&D programs in Influenza, COVID-19 and the T-cell-based viral vector platform, where appropriate, we will seek strategic partners to continue development of these assets. We are also implementing a workforce restructuring that will result in a reduction of approximately…

Thank you, Brent. As we have shared previously, our goal is to become a sustainable, fully integrated commercial company, and we have committed to utilize our strong cash position to invest in complementary attractive clinical stage assets. We have committed to leverage our scientific expertise, our proprietary antibody platform and our capabilities to broaden our aperture beyond infectious diseases. We have committed to increase our financial discipline and build a more fit-for-purpose organization, and we have committed to sharpen our investment focus on areas where we can make the greatest impact on patients as value creation. Starting the close of the license agreement with Sanofi and coupled with our strategic restructuring, we will have successfully delivered on all of these commitments. Looking ahead, we will be positioned well with a focused set of development priorities to accelerate near-term value creation. Our development priorities include promising programs in hepatitis delta, hepatitis B and the newly licensed T-cell engagers. We are looking forward to sharing more with you on these programs as well as our earlier stage programs during our R&D Day in late November. As we look to the future, we are excited about the multiple value-driving catalysts anticipated across our pipeline in the next four to 18 months. We expect to report additional clinical data from our hepatitis delta and our hepatitis B program later this year, as well as share updates subject to closing on the progress of our newly licensed T-cell engagers during the course of 2025 and 2026. These milestones highlight the potential of our pipeline to deliver meaningful near-term value. In conclusion, today marks a pivotal moment for Vir as we embark on a new chapter in our journey of powering the immune system to transform lives. With a strengthened pipeline, our talented team and a clear vision for the future, we are well-positioned to deliver on our mission and create long-term value for all our stakeholders. Thank you for your continued support and your interest in Vir. We look forward to keeping you updated on our progress. And with that, I'll turn the call back to Rich to begin the Q&A session.

Thank you, Marianne. We will now start the Q&A session. Please limit questions to two per person so we get to all of our covering analysts. I'll turn it over to you, operator.

Thank you, Rich. At this time, we will begin conducting our analyst Q&A session. [Operator Instructions] Our first question comes from Phil Nadeau with TD Cowen. Please go ahead.

Good afternoon. Thanks for taking our questions and congratulations on the deal. Two for us on the new molecules. I guess, first, on 6309 and 6329, the dose escalation phases that are ongoing now from which we'll get data next year. Are those in unselected patient populations kind of all comer refractory patients? Or are they being -- are HER in PSMA specific patients being enrolled in those trials. That's the first question. And then second, more broadly, can you give us some idea of the framework by which you'll evaluate all three of the TCEs to continue investment and move forward. This sounds very, very interesting. Nonetheless, there are other agents, obviously already in the market or in development targeting PSMA, HER and EGFR. So what -- broadly, what do you hope to see? Do you want to see best-in-class, simply competitive enough or do you expect there to be populations in which these work that some of the other agents do. Thank you.

Thank you, Phil. Appreciate the question. So maybe I'll ask Mark, our CMO, to address your first question.

Sure. And I appreciate the question. I think it's a really good one. For both 6309 and 6329, we are, as you said, enrolling tumor types that are heavily pretreated. In the case of 6309, both HER2-positive -- HER2 high and HER2 low patients are being enrolled. For the PSMA program, there's not a specific requirement for PSMA positivity, but that certainly will be something that's looked at. In terms of your question about the framework for how the assets will be evaluated. The Phase 1 studies allow both dose escalation to test the hypothesis that we can achieve a superior therapeutic index with better safety and efficacy than unmasked TCEs can achieve. So that's one point. The second point is that it allows for potential expansion cohorts in the different diseases, both in monotherapy and in combination therapy. So as the data evolve, we'll be able to determine what are the most promising tumor types combinations versus monotherapy. In terms of very specific hurdles or bars, I think that's something I'll have to get back to you on a subsequent call. But what I would end with saying is that the way the program is currently designed will allow a very intensive interrogation of monotherapy, combination therapy in a variety of tumor types and in the case of PSMA in prostate cancer.

That’s very helpful.

Yeah. The only thing I would add there, Phil, is as we discussed, I mean, the unmet medical need is still incredibly high in each of these areas for two cancers and PSMA cancers. And there is no TCEs approved in either of the areas that we are discussing today.

That's very helpful. Congrats on the deal and thanks for taking our questions.

Thank you.

Our next question comes from Roanna Ruiz with Leerink. Please go ahead.

Hey, good afternoon. This is Nick Gasic on for Roanna. Thanks for taking our questions. Maybe first from us on the new deal with Sanofi. I guess what are the three T-cell engager programs are you most excited about? I'm curious what your thoughts are on the competitive positioning across the three? And I have a follow-up on HDV.

Yeah. Thank you for that question. I'll start and then also ask Mark to chime in. Just again to reiterate for HER2 PSMA and EGFR, even though those are obviously biologically well-validated targets, and there's a lot of activity that has been going on, on these targets. I think that if you look at the landscape today, again, there's still a very high unmet medical need, high mortality for people diagnosed with HER2 cancers. Again, we talked about only 34% of patients being alive after five years diagnosed with PSMA prostate cancer and then only a five-year survival -- a 5-year survival rate of really being very low between 3% and 38% for EGFR-related cancers. So the unmet need despite everything that might be approved or in development is incredibly high. There are no T-cell engagers for each -- any of these targets that are currently being approved. And again, despite other modalities being approved, especially for HER2 PSMA, you are still faced with this high mortality and a lot of challenging side effects for patients. So the unmet need remains and we think that's really in each -- for each of these therapeutic agents an opportunity to potentially really drive the differentiating impact for patients. Mark, do you want to add?

Sure. Thanks, Marianne. So what I would note that these are all clinically validated targets. So we're very excited about all three of them. They are in different phases of development. The HER2 program is furthest along in the clinic, and so we're getting efficacy -- preliminary efficacy and safety data in these patients with multiple tumor types. And I think there's an opportunity to be first to achieve clinical proof-of-concept within a TCE. For PSMA, we're in Phase 1 as well, GenX [ph] offers a powerful proof point for the approach, which is another asset also in Phase 1. And the other thing I would add is that because of the universal masking, we're able to leverage to 6309 HER2 program to dose escalate more quickly in the PSMA program. And then EGFR, which as we have said before, is looking to go to Phase 1 early next year in Q1 is a potential high risk, high reward opportunity. There's multiple competitors in the clinic three, but there's multiple tumor types that are EGFR positive. And I think here, the potential of the masking is really impactful because this is such a widely expressed marker or a molecule that in order to achieve a therapeutic index that can actually treat the cancers with acceptable safety. This is where I think the exciting aspect of the EGFR program is.

Got it. Thanks for that color. Maybe second question just on HDV. Curious how your interactions with the FDA has been going after the recent HDV data at EASL. And maybe curious what your latest outlook is on a potentially accelerated approval pathway here. Thanks.

Yeah. So good question. So we already announced that we have fast track designation from the FDA, which I think speaks to the high unmet medical need and the very compelling clinical data. We are pursuing other accelerated clinical development pathways such as breakthrough therapy designation, and we are pursuing an engagement with FDA starting this quarter, Q3 to talk about the registrational program. So we're very excited about the Delta program. We're moving quickly to fit into registrational studies.

That’s helpful. Thanks.

Our next question comes from Paul Choi with Goldman Sachs. Please go ahead.

Hi. Thank you. Good afternoon, and let me also offer my congratulations on the deal. My first question, either for Jennifer or for Mark is, can you maybe share any additional insights with regard to the safety profile of our -- of the T-cell engagers that you just in-licensed with from Sanofi, particularly with regard to anything in healthy volunteers that would suggest that you can avoid some of the issues with cytokine release syndrome that have been a hallmark of the class and just any other evidence you can share with regard to the safety profile? And then my second question, more for Mark probably is, as you think about prosecuting next stage clinical trials after the dose escalation studies, can you comment on your ability and the company's ability to pursue multiple drugs here, I guess, in the clinic at the same time? Or will you prioritize one over the other, depending on the dose escalation data?

Go ahead, Mark.

Sure. Thanks, Paul, for the questions. In terms of the safety data, the first thing I would mention is the preclinical data that Jen described in detail that shows the fact that there's a 10,000-fold reduction in potency in the mass state as opposed to in the tumor microenvironment where the molecules are activated and form immune synopsis with the tumor cells. We have had the opportunity during the diligence to look at preliminary clinical data, including safety data. It's been very valuable to be able to see that. We're not on the able to comment on that today, but I can say that we gained some valuable insights that gave us confidence to move into prosecuting the deal. In terms of the next stage clinical trial, it's great questions about that. In terms of our development capabilities, I think Vir has demonstrated that we can run large trials at scale, including the peninsula trial of influenza prevention, 3,000 or so patients, multiple Phase 1 and 2 studies subcutaneously in Delta. And we -- bringing on the Sanofi employees, I think we see a lot of synergies between what we can provide in terms of clinical operations, regulatory and other infrastructure and their knowledge and in-depth experience with these assets and their deep relationships with the KOLs and the sites. I feel confident that we'll be able to prosecute multiple trials simultaneously. That, of course, we'll follow the data. We'll prioritize programs that have the most compelling clinical data as those data evolve.

Okay. Great. Thank you for taking our questions.

Our next question comes from Eric Joseph with J.P. Morgan. Please go ahead.

Hi. Thanks for taking the question. Maybe just one or two on 6309. As the trial is designed, it contemplates a combination with PD-1 pembrolizumab, maybe you can shed some light on the biological rationale behind that combination. Is -- are any PD-1 thought to be potentiators of T-cell engagers and any visibility that you might have at this stage on the safety of that combination so far.

Hi. This is Jen. I can start with that. So maybe I'll start and then hand it over to Mark along the ideas of the safety. So I think fundamentally, what a T-cell engager requires is both the targeting the tumor with the tumor-associated antigen and an activation of the T-cells through the CD3 arm. This informs the immune synapse allows the T-cells to directly kill the tumor cells. This requires that you have T-cells there that can be activated. And so there's where I think you have real synergy with something like a PD-1, which really removes a break on a T-cell and it allows them to be active. So that's really the fundamental concept behind us of a checkpoint inhibitor with a T-cell engager.

Yeah. In terms of the safety of dose escalation in combination with pembro, I'll just refer to my prior statement, which is we have had the opportunity to see preliminary clinical data, including safety data and preliminary efficacy data. And we found this information really valuable. We're not really able to comment in detail on that at this point, but this is information we'll be providing as a subsequent interaction.

Okay. Great. Well, thanks for the great color and congrats on the deal.

Thanks Eric.

Our next question comes from Mike Ulz with Morgan Stanley. Please go ahead.

Yep. Hey guys, thanks for taking the question. Maybe just now that you have this PRO-XTEN masking platform, you mentioned the potential to leverage it with your own monoclonal antibody platform. Can you maybe just give us a sense where you initially think you might go with your next-generation antibodies that could be masked now or any particular targets you might be interested in? Thanks.

Jen, do you want to take that?

Yeah. No, thank you for the question. So I do think there are real synergies. I mean, fundamentally what the T-cell engagers are is that they are built off of the antibodies. And so these single-chain SVs, which are the binding portion of the antibody. So our antibody discovery engine really does provide quite complementary and synergistic at power to developing the next stage of T-cell engagers. I think as you can see by the first three molecules, and they really have focused in on ones that -- for which there is biological proof-of-concept for these being bonafied tumor-associated antigens. And frankly, there's a number of others that one could consider developing. I think that's where it will start. I do think the platform has really broad potential and brought up facility. The first time in XTEN was used with this molecule ALTUVIIIO, which was really just used to extend its half-life. I think from that, it's been shown that it can be applied to not only T-cell engagers, but also to other biologics, including cytokines and probably antibodies as well. So I think there really is a broad potential of this, but I think focusing first on those that have biological proof-of-concept and an extent from there.

Got it. Thank you.

Yeah. The only thing I would add is if you think about these as T-cell engagers and the components of it, as Jen was saying, I mean, on the T-cell engagement side itself, the therapeutic modality, I think we can contribute tremendously with our antibody engineering expertise. And then what is also, I think, very encouraging is that both on the masked side, as Jen said, there's a considerable amount derisking that has happened given that there's a drug on the market that has been using this month. And also on the cleavable linker side, I think you have seen what Jen presented on the preclinical data, which is very convincingly showing, of course, preclinically in vitro and in vivo that this actually works. So I think there's a lot of derisking that has been on the platform. And as it relates to then really going for new targets, I think we can add a really unique capability.

Great.

Our next question comes from Joseph Stringer with Needham & Company.

Hi. Thanks for taking our questions. You mentioned the broad potential of the platform and the in-licensed assets. Just curious if you could provide some additional color behind the decision for the in-licensing and with the move into oncology intentional, were there other assets and other therapeutic areas that were considered? And then lastly, does the update -- corporate update here, does that affect any of the time lines or any of the resources that you can devote to the HBV or HDV programs? Thank you.

Yeah. Thank you for that question, Joe. So the corporate update, absolutely no impact on our time lines for the hepatitis delta and hepatitis B studies. I mean, our focus will be on clinical execution that is really a strategic priority for hepatitis programs and then after closing of this transaction also the newly licensed T-cell engagers. Now coming to your earlier question about how we came about the decision. So during the course of, I think, the last year, we have said that we want to be really strategic and thoughtful about how we would be using our cash balance, which, as Brent mentioned, was $1.43 billion at the end of the second quarter. and that we would be looking for potentially bringing in a clinical stage asset or assets and really look for opportunities that would build strongly on our existing expertise. So really opportunities where there would be strong synergy. So obviously, we have looked at a lot of opportunities that would fit that mold. But I would say that we really believe this is a very, very unique fit for a lot of different reasons. Obviously, the start -- the opportunity addresses a very high unmet need. We talked about it. And we did very rigorous due diligence, and we came away very convinced about the value of the clinical assets, but also really the value of the platform and the signs behind it. As we said, the targets, the biological targets on the three clinical assets are derisked. The masking is, to some extent, derisked and the cleavable linkers, again, we have very strong preclinical data in vitro and in vivo to show that this actually all. So -- and again, in addition, highly synergistic, as we discussed with every capability that we have here in-house, our antibody expertise, our clinical development organization that has proven to be very, very strong in operating on clinical trials and also our deep immunology expertise and B and T-cell expertise, which we haven't talked about that much. And then finally, this deal brings a number of near-term catalysts and value infraction points for the company. Within the next nine to 18 months, we will really be able to see data on these clinical stage T-cell engagers. So that's all taken together, very, very excited and a great moment for us here at Vir.

Our next call -- our final call for today comes from Alec Stranahan with Bank of America. Please go ahead.

Thanks, and appreciate you taking more questions. Two from us. First, just on the new TC assets. Just trying to understand the competitive positioning a bit more. Anything unique that you could point us to in terms of the design of the mask versus, say, a GenX or CytomX? Or is it more due to the fact that you're using a mask on both the antitumor and the anti-CD3 arms versus the actual structure of the mask itself? And then I've got a follow-up.

Jen, do you want to take that?

Yes, sure, happy to. So really, I think that the uniqueness is actually in the combination of attributes for this platform. And so I spoke about this, but it was at a fairly high level. So let me elaborate a little bit more. So I think there's some major components. One you hit upon. One is the dual masking. So I think there provides a real advantage to masking both the tumor-associated antigen as well as the CD3 arm and both arms can because of safety issues. And so masking both of them really has the best potential to eliminate those issues. Importantly, this is also different design, and it's a universal mask. So that's where it comes with this like plug-and-play concept, and that the same mask can be used across multiple different therapeutics. So essentially, the same mask is on all three of the T-cell engagers that are in or close to the clinic. And this allows for rapid execution, both preclinically, but also rapid execution in the clinic. As Mark highlighted, this does make a quicker path towards dose escalation for PSMA because the mask itself has been derisked. And ALTUVIIIO itself does also derisk the mask. So there has been an approved product for which this mask is used, providing additional concept around its safety as well as lack of immunogenicity. And then finally, I think the other component that we've hit on that I think is also quite exciting is this broader applicability of the masks, not only for T-cell engagers, but also potentially for other molecules like cytokine or potentially other protein therapeutics like antibodies.

Okay.

Alec, I would just add that from a competitive landscape perspective, for HER2, there's no other masked T-cell engagers in development. For PSMA, there is one mask TC in development and for EGFR, there are three. So I mean, in the broader context of things here, where TCEs, as we discussed, have a lot of shortcomings and a lot of toxicity and really challenging profiles for patients. We have an opportunity here through this masked TCEs to really drive the difference and the competitive landscape is really not that intense.

Okay. Thanks. That's clear. And then maybe one quick one, just putting a finer point on the applications in immunology. Would this mostly be through half-life extension for, say, cytokines? Or are there any targets or indications you think could be the most apt initial avenues for development? Thanks.

Yeah. So we can't extend the half-life, but I think actually, there are two attributes. So the way that the mask is used in ALTUVIIIO is purely fixed on the half-life. The way the mask is used for the T-cell engagers is that it does extend the half-life and allows them to get to the site of action. However, once they are cleaved, they don't have a very short half-life, which then allows them to act in that tumor microenvironment, because they're right there with their target antigen. It activates the T-cells, which then have a longer list and activation profile. But that active molecule once it circulates, then has a very short half-life, and that provides an avid safety benefit. You can envision the same type of thing being applied to a cytokine, having it be activated only at the site where you want it to be activated and then having that short half-life be an attribute, because we all know that these cytokines will incredibly potent and beneficial for activating immune cells, they often have very high associated toxicity themselves. So while they have a short half-life, you don't want them to have too long at half-life or you're going to have greater toxicity. So I think those both are true. Thank you for the question.

Thank you.

All right. This concludes the Q&A session of the call. Thank you for participating, and I'll turn the call back over to Marianne. End of Q&A:

Yes, apologies. Thanks everyone for your interest in listening to our earnings call today, and people [ph] will put that close call. Thank you.