[Call starts abruptly] …Vir's Third Quarter 2024 Financial Results and Business Update Call. As a reminder, this conference call is being recorded. [Operator Instructions] I will now turn the call over to Rich Lepke, Senior Director, Investor Relations. You may begin, Mr. Lepke.

Thank you and good afternoon. With me today are Dr. Marianne De Backer, our Chief Executive Officer; Dr. Mark Eisner, our Chief Medical Officer; and Jason O'Byrne, our 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, Marianne De Backer.

Thank you, Rich. Good afternoon, everyone and thank you for joining us today. I'm pleased to provide an update on the significant progress we've made this quarter, beginning with the successful closing of our exclusive worldwide licensing agreement with Sanofi. This landmark agreement includes 3 clinical stage masked T-cell engagers and use of Sanofi's proprietary PRO-XTEN protease-cleavable masking platform for oncology and infectious diseases. This strategic move aligns seamlessly with our mission to use the power of the immune system to fight disease. We believe that the 3 dual-masked T cell engagers VIR-5818 for HER2, VIR-5500 for PSMA and VIR-5525 for EGFR have the potential to be best-in-class therapies. These investigational treatments aim to minimize toxicity challenges typically associated with T-cell engagers, allowing for higher dosing and thereby enhancing efficacy. As part of this agreement, we have welcomed key employees from Sanofi which bring extensive scientific and development expertise in oncology and the PRO-XTEN masking platform technology. These talented individuals have quickly proven to be an excellent fit within our organization. We believe that their expertise, combined with our deep understanding of T-cell immunology, our robust infrastructure and leading machine learning and antibody engineering capabilities will create significant synergies. Moving on to our mid-stage clinical pipeline. We are making strong progress across our hepatitis programs with important upcoming data readouts. I'll now highlight our recent progress in the ongoing Phase II SOLSTICE trial in patients with chronic hepatitis delta. Hepatitis delta represents a highly promising growth opportunity for Vir, marking the next significant inflection point in our journey towards becoming a fully integrated and sustainable commercial company. Much like other orphan disease markets, the HDV market is characterized by significant unmet medical needs and severe clinical outcomes for patients. This underscores an opportunity for innovative and impactful therapies that address…

Thank you, Marianne and good afternoon, everyone. Let's begin with the SOLSTICE trial in hepatitis delta. As a reminder, we presented strong preliminary data from our Phase II SOLSTICE trial in HDV at the EASL Congress in June. In our rollover cohort of 6 non-cirrhotic participants, we reported that all 6 achieved virologic suppression below the lower limit of quantification and 5 out of 6 achieved target not detected indicating no measurable presence of HDV RNA. Additionally, 3 out of 6 achieved ALT normalization, durable virologic suppression was observed in the combination rollover cohort, suggesting the potential for sustained antiviral activity. There are 32 participants in the de novo combination cohort and 33 participants are in the monotherapy cohort. At the time of the analysis, 11 participants in the de novo combination cohort and 7 participants in the monotherapy cohort had reached 24 weeks of treatment. There were no discontinuations in the combination cohort. After 24 weeks of treatment, all 11 participants in the de novo combination cohort achieved virologic suppression below the lower limit of quantification and 6 out of 11 achieved target not detected. Seven out of 11 also achieved ALT normalization. From a safety perspective, we observed no treatment-related serious adverse events or ALT flares in either the monotherapy or de novo combination treatment regimens. The majority of adverse events were transient and mild grade 1 or 2 with a low incidence of injection site reactions. Taken together, these preliminary data are extremely promising as all 3 cohorts demonstrated rapid and sustained virologic responses. We will be sharing the full data set for both cohorts of approximately 30 participants at 24 weeks of treatment as well as available data for participants beyond 24 weeks of treatment at AASLD. We are pleased to have received Fast Track Designation…

Thank you, Jason. This concludes our prepared remarks and we will now start the Q&A section. [Operator Instructions] I'll turn it over to you, operator.

[Operator Instructions] We'll go first to Paul Choi at Goldman Sachs.

My first question is, can you just update us on the status of your planned end of Phase II meeting with the FDA? Apologies if I missed a mention of it in the press release. So I was just curious what the status of your regulatory discussions was? And my second question is for your new T-cell engager program for 5818. Can you maybe comment on how you're thinking about the relative measures you're looking for, for both the monotherapy versus the pembrolizumab combination?

Thank you very much for the question, Paul. I give it to Mark, our CMO, to answer those questions.

Yes. Thanks for the question, Paul. We have engaged with the FDA as you mentioned. We are just putting the very finishing touches on our clinical development program and we expect to be able to share further details about that at our hepatitis focused investor meeting on November 19. In terms of the T-cell engager program in the 5818 HER2xCD3 program, in particular, your question about efficacy is a good one. We are planning to share preliminary monotherapy data from that program, also the PSMA program in quarter 1 next year. And at that time, we'll be able to provide a bit more perspective on the data.

Next, will go to Eric Joseph at JPMorgan.

If I remember correctly, just in terms of the pivotal path forward in HDV, you previously outlined a randomized study with Hepcludex as a comparator arm. I guess based on your latest regulatory interaction, should we still kind of carry at that expectation? And I guess within that, how should we be thinking about sort of the continued inclusion of -- or evaluation of combination or monotherapy with tobevibart?

Yes. Thanks for the question. So as we've stated before, we are committed to going forward with a combination of tobevibart and elebsiran because we achieved deep and sustained virologic responses with the combination regimen. And to remind everyone, we got Fast Track Designation for the combination regimen for the FDA. In terms of further details of the program, we do plan on discussing this in more detail in our investor event around AASLD.

We'll move next to Mike Ulz at Morgan Stanley.

Maybe I could just ask a follow-up on the Phase III trial design and your interactions with the FDA. I'm just curious if you're getting any feedback that might be unexpected at this point? Or are things just on track and you're going to sort of reveal the final details at your investor event?

Yes. Thank you for the question. I will say we had a very productive meeting with the FDA. I think we aligned with them very closely on the plan and we'll be prepared to share more details at the investor event around AASLD.

Next, we'll go to Gena Wang at Barclays.

I have two questions. The first one is regarding the HDV data. Thank you very much to putting the data together from the prior study. So Slide 21, you lay out the several data points here. But I assume the key focus for us should be the target not detectable rate and also ALT normalization. Should we expect those are the benchmark and that should be the level -- minimum level should achieve with more patient data now, 32 patients, 33 patients at week 24? And my second question is regarding the T-cell engagers. I remember, Marianne, you said you saw some initial Phase I data when the Sanofi deal discussion was ongoing. So now with the next year data update, have you seen the more patient data? And with the more patients, does the monotherapy activity hold as your initial expectation?

Okay. Thank you very much, Gena. Mark, do you want to comment on the HDV data?

Yes, absolutely. So this SOLSTICE study in HDV, we're going to have an oral presentation at the AASLD meeting which I think will give a lot more information, particularly all the patients made it through week 24 of the study and some of the patients beyond that. So we're going to be presenting those data. In terms of your question around TND, yes, absolutely. I mean getting below the limit of quantification target not detected means there's undetectable delta viral levels. So that is kind of the most rigorous measurement that's out there. Our combination regimen what we revealed at EASL is a very, very profound reduction in the viral load in achieving high rates of target not detected above 50% at week 24. In terms of ALT normalization, that's also important and those data will be included. The FDA guidance include a composite endpoint of TND plus ALT normalization. So that will be data we will also present at the AASLD meeting coming up.

Yes. And then on your question related to the T-cell engager, Gena, remember that our agreement with Sanofi closed on September 9. So we are in the midst of transitions, for example, trial sponsorship and so on. Obviously, we have all the data available on the programs. And as I mentioned, we will be in a position to share initial data on the monotherapy of both the 5500 and 5818 assets in the first quarter of 2025.

We'll move next to Alec Stranahan at Bank of America.

Two for me as well. I was hoping you could help frame the sort of data we should expect for 5818 and 5500 in the first quarter. Will it be mostly focusing on maybe safety and dosimetry or could we see some initial efficacy metrics as well? And if you could speak to how the dual-mask for your assets might benefit your ability to reach a higher target dose? Is this baked into the dose escalation? Or is driving to reach MTD, maybe not even the right way to be thinking about things here?

Sure. So in terms of your first question, we -- as we stated, we are planning to share preliminary monotherapy data from the ongoing Phase I studies both for VIR-5818 HER2 program and VIR-5500, the PSA T-cell engager program. At this point, we're not really providing more color on that but we will be providing most data updates in quarter 1 of next year. And then your question about the dual-masking, I think, is important. All of our programs do have the dual-masking. So we're masking both the CD3 T-cell engager part of the molecule and the tumor antigen binding part of the molecule. So the working hypothesis here is that, that will allow us to achieve a better therapeutic index. So higher levels of safety -- I mean, higher levels of efficacy with good safety. As we mentioned before, for the HER2 program, we're the only dual-masked program in clinical development for PSMA. The Janux program masks the CD3 part but leaves the PSMA unmasked. So we think we may have a differentiated asset in terms of our dual masking of the PSMA molecule.

We'll go next to Roanna Ruiz at Leerink Partners.

This is Nik Gasic on for Roanna. Maybe first on the HDV Phase III trial design, thinking about the target patient population. Are you going to be focusing on those cirrhotic and non-cirrhotics. And I guess, are there any specific baseline characteristics you could enrich for here? A quick follow-up on HDV after that.

Sure. So thanks for the question. In terms -- so in SOLSTICE, we presented data, including both cirrhotic and non-cirrhotic patients, CPTAs and back in EASL, when we presented these data, you'll recall that the antiviral efficacy effect on ALT was very, very good in both cirrhotics and non-cirrhotics. If anything, the cirrhotic patients fared a little bit better. So clearly, we want to base our Phase III program on the observations from the Phase II program so we would include both cirrhotic and non-cirrhotic patients. In terms of baseline characteristics, that kind of predict response in any enrichment, I think we'll be able to provide more color on that at our investor-focused hepatitis presentation around AASLD. So stay tuned for more detail there.

Got it. That's helpful. And then in HBV, looking ahead, what sort of read-through could the 48-week end-of-treatment data have to the possible functional cure data in the second quarter of '25. Just curious what sort of HBs antigen suppression rates, you could see at the 48 weeks, how that might mature heading into the off-treatment data in 2Q?

Yes. No, that's a really good question. So just to summarize, we'll have the end-of-treatment data for the doublet of tobevibart and elebsiran and the triplet with pegylated interferon in addition of the upcoming liver meeting in San Diego. The functional cure data, as you said, comes in Q2 next year. So really, what we said before for functional cure is we're looking for a minimum of 30% in the triplet functional cure, 20% in the doublet. In terms of end-of-treatment data, it's clear that there is going to be at least based on prior programs of various mechanisms of action, there's a drop-off between end-of-treatment in 24 weeks post treatment to a functional cure. But predicting that drop-off is not straightforward and there is no clearly establish markers to do that. So what I'd say, just in summary, is we will have end-of-treatment data soon. The functional cure rate will take a little bit longer, Q2 next year. And taken together, that will give a very complete picture of the regimens and what they can achieve for HBV patients.

We'll move next to Phil Nadeau at TD Cowen.

Two from us. So first, on the HDV pivotal program, you've suggested you'll be able to give us an update at the AASLD Analyst Meeting. Will you have the final trial design at that time? And would you be able to disclose the design and time lines at the meeting? That's the first question. And then second question, just broadly on the TCEs. You mentioned the potential for differentiation versus either other TCEs in development or just broadly in the spaces of HER2 and PMSA to begin. Do you need to see differentiation in order to move those beyond Phase I? Or is simply safe and effective good enough at this point with additional differentiation to be established in future studies?

So for the HDV question, we are planning to disclose more information about the final trial design, the Phase III design. So you'll be able to see that at the investor event around AASLD. So that more coming there. In terms of time lines, right now, we're not disclosing additional information about that and we will look to do that when we have full clarity on time lines. In terms of the TCE question, Marianne, would you like me...

Sure.

Okay. So your question is around what we would need to see to move these programs forward for HER2 and PSMA. To be honest, really something that is going to be a data-driven decision. I think we are looking at this very early stage, of course, to look at proof of concept, then the preliminary monotherapy data that we'll present in quarter 1, I think we'll give -- start to give a picture of what the programs look like. In terms of the more specific answer to your question, I think we're quite ready to opine on that yet but we will look to provide more color on that at a future time point.

And we'll go next to Patrick Trucchio at H.C. Wainwright.

Just a couple of follow-up questions for me. First, in the HDV program, can you discuss more how the combination of elebsiran and tobevibart would be expected to be different from bulevirtide including at higher doses and the level of confidence that patients would maintain ALT normalization and virologic response to switch from bulevirtide to the combination treatment regimen based on what we've seen in the clinical data so far. And then separately, with the HBV program regarding the 20% functional cure rate without interferon and 30% functional cure rate with interferon. Can you tell us if these rates would be anticipated in all-comers? Or is it in the low S-antigen at baseline patients? And if we look ahead to a potential Phase III pivotal program, can you talk about or tell us more if you're thinking about maybe stratifying base on S-antigen at baseline, would it make sense to explore combination -- this combination in patients with low S-antigen at baseline?

Okay. So on your first question about HDV. The first part of that was about the combination of tobevibart and elebsiran versus bulevirtide. We do -- with the 2-milligram improved dose, we do expect to get much higher levels of target not detected based on our data we presented at EASL than bulevirtide which is 12% at 48 weeks. Your question about the higher dose, I mean that dose isn't really -- isn't approved anywhere. So -- but even so I think the level of TND efficacy that we expect to have should be superior to bulevirtide just thinking about what we're likely to see. In terms of level of confidence from bulevirtide switch, yes. I mean in terms of the patient population who has been on bulevirtide who is likely to enter such a trial or in a clinical practice, we would expect to be much higher in terms of our virologic response with our combination and continued treatment with bulevirtide. In terms of your HBV question, fundamentally, I think your question is around is this going to be an all-comers versus a stratified population based on baseline surface antigen. I guess I'd just ask you to stay tuned for the data and those questions should become much clearer at the March presentation at the liver meeting.

And this concludes the Q&A session of the call. Thank you for participating and I'll turn the call back over to Rich.

Thank you all for your interest in Vir and for participating in today's earnings call. We appreciate your continued support and look forward to providing further updates on our progress in the future. Andre, this concludes our call. Thank you, you may close the call.

Thank you. And that does conclude today's conference call. Thank you for your participation. You may now disconnect.