VIR - NASDAQ

Hello. Welcome to Vir Biotechnology's First Quarter 2025 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. 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; Jason O'Byrne, our Chief Financial Officer; and Dr. Mika Derynck, our Executive Vice President of Oncology, who will be available during the Q&A session. 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 Barker. Please go ahead.

Thank you, Rich and good afternoon, everyone. Thank you for joining us for VIR Biotechnology's first quarter 2025 earnings call. I'm pleased to share our progress and achievements with you today as we continue to execute on our strategic priorities. Before we dive in, I want to express my gratitude for your continued support and interest in our mission of powering the immune system to transform patients' lives. We've had a strong start to 2025 with meaningful progress across our pipeline. Our strategic focus on advancing both our infectious disease and oncology programs continues to position us well for future growth and value creation. I'm pleased to share that we successfully initiated our ECLIPSE Phase III registrational program with the first patient enrolled in ECLIPSE-1 during the first quarter. This is a significant milestone in our commitment to develop a potential new standard of care for patients with hepatitis delta virus infection. The ECLIPSE program builds on our SOLSTICE Phase II data which demonstrated impressive virological responses with our combination therapy. Today, I'd also like to provide our refined assessment of the hepatitis delta market opportunity which reflects the prelaunch work we have initiated in parallel with our Phase III trials to better characterize the addressable patient population. Based on our comprehensive market analysis, we estimate that there are approximately 7 million active viremic HDV RNA positive patients globally. In the United States, we estimate approximately 61,000 RNA-positive patients. In the EU member countries plus the U.K., we estimate approximately 113,000 RNA-positive patients and additional geographies beyond these could represent long-term opportunities. I want to emphasize that these figures specifically focus on RNA-positive patients with active viremic disease who would be candidates for treatment. This distinction is important because we focus specifically on patients with detectable viral replication who face the highest risk of disease progression. We've conducted an extensive evaluation of multiple epidemiological sources and consulted with leading experts in the field to arrive at these estimates. It's important to note that our updated understanding of the market size underscores that hepatitis delta has the characteristics of a rare disease market with significant commercial potential. Let me highlight a few key points. First, this is a disease with severe outcomes. More than 50% of hepatitis delta patients succumb to liver-related death within 10 years of diagnosis and there are no FDA-approved treatments in the United States. Second, treatment is managed by a concentrated group of hepatologists and liver specialists, allowing for a focused commercial engagement. Third, the severe clinical outcomes and EMA orphan disease designation support a value-based pricing model, similar to other rare disease therapies. Fourth, the high cost burden of untreated disease progression, including liver transplantation and end-stage liver disease management provides a compelling economic case for effective treatment. And finally, our market research indicates high physician intent to treat these patients given the lack of effective options. The regulatory designations we've received breakthrough therapy, Fast Track in the United States and prime and orphan drug in the EU underscore the potential impact of our approach and may help accelerate our development time line. We are focused on driving enrollment in our ECLIPSE-1 trial and preparing for the ECLIPSE 2 and 3 study initiation. As we advance our hepatitis delta program, I'm also pleased to report that during the quarter, we reached an agreement with Alnylam, whereby they elected not to opt into the profit-sharing arrangement for elebsiran, resulting in a continued milestone and royalty-based structure. This decision provides clarity for our approach to advance our hepatitis delta program and gives us the flexibility to partner the program in Europe and other international markets. The outcome of this agreement was anticipated and factored into our long-term financial planning and was already included in our projected cash runway extending into mid-2027. Jason will provide additional details on the financial aspects of this agreement later in the call. Turning briefly to our hepatitis B program. We are presenting 24-week post-treatment follow-up data from our MARCH Phase II study at the upcoming EASL Congress on May 9. Specifically, we will be sharing functional cure data from participants who have completed 24 weeks of follow-up after treatment discontinuation. Shifting gears to our oncology portfolio. We continue to make steady progress with the PRO-XTEN Dual Masked T-Cell Engager program. As a reminder, we have worldwide rights to the PRO-XTEN platform in infectious disease and oncology. For VIR-5818, our dual mask to HER2 targeted T-cell engager, we are continuing to dose escalate as monotherapy and in combination with pembrolizumab. Our data presented in January showed a 33% confirmed partial response rate in HER2-positive colorectal cancer patients at doses of 400 micrograms per kilogram and above with 1 response lasting over 18 months. We are particularly encouraged by these results in colorectal cancer, where there remains a significant unmet need for effective therapies. These responses were observed in microsatellite stable tumors which are typically resistant to immunotherapy, suggesting VIR-5818 could potentially address an important treatment gap for these patients. For VIR-5500, our dual masked PSMA targeted T-cell engager, we continue to dose escalate given our favorable safety profile and the learnings from VIR-5818. We've evaluated multiple additional dose levels since our last update. Our January data showed that 100% of patients at doses above 120 micrograms per kilogram experienced PSA declines with 58% achieving a PSA50 response, all without prophylactic steroids and with minimal cytokine release syndrome. We continue to see strong investigator enthusiasm for this program based on the early signals we've observed. We're also on track to initiate our Phase I study for VIR-5525, our dual masked EGFR targeted T-cell engager this quarter. This program has the potential to address multiple high-value indications, including non-small cell lung cancer, colorectal cancer, head and neck squamous cell carcinoma and other EGFR-expressing tumors. The PRO-XTEN universal dual masking approach continues to demonstrate potential advantages in terms of safety profile and dosing flexibility. Beyond our clinical stage programs, we are rapidly advancing several next-generation targets in areas of high unmet medical need. Our antibody discovery and protein engineering capabilities are key to the discovery of new tumor-associated antigen binders to quickly advance new TCE programs. And the universal nature of the PRO-XTEN platform allows us to efficiently apply our dual masking approach. The synergies between antibody discovery capabilities and the PRO-XTEN platform have begun to translate into meaningful progress with 7 targets progressing in preclinical development across a number of solid tumor indications with high unmet need. These research efforts represent important long-term value drivers for our oncology portfolio. We're also exploring potential collaborations that could further unlock and maximize value from the PRO-XTEN platform. Additionally, leveraging our expertise in infectious disease immunology, we have advanced a broadly neutralizing antibody to development candidate status in our HIV cure program. Looking ahead, our financial position remains strong with approximately $1 billion in cash, cash equivalents and investments at the end of the first quarter. This provides us with cash runway extending into mid-2027, giving us the resources to advance our key programs through critical value inflection points. We're maintaining a disciplined approach to capital allocation, focusing our resources on our most promising programs. As we continue to execute on our strategic priorities, we recognize the challenging market environment facing the biotechnology sector as a whole. In times like these, we believe the most important thing we can do for our shareholders is to remain focused on operational excellence and advancing our pipeline with discipline and purpose. Our strong cash position allows us to weather market volatility. I'm confident that our focused approach to developing potentially transformative medicines for patients with significant unmet needs will make a difference in the lives of patients while driving value creation for our shareholders. With that, I'll now turn the call over to Mark to provide a more detailed update on our clinical development programs.

Thank you, Jason. This concludes our prepared remarks and we will now start the Q&A session. Please limit your question to 2 per person so we can get to all of our covering analysts. I'll turn it over to you, operator.

[Operator Instructions] Your first question comes from the line of Gena Wang with Barclays.

I have 2 questions. So maybe the first one regarding the Alnylam decision. Did they see most up-to-date data for both HBV and HDV? And what was the reason they provided for not opting? And the second question is thinking about you have so many programs progress so rapidly in the oncology space. So when should we see the next update from the programs and which will be likely the venue when we'll see those data update?

Yes. Thank you, Gena, for those questions. Maybe I'll start with the last one first. So when the next oncology data update will be coming. So the way we think about it for any next data update, what we would be anticipating to share is, first of all, obviously, more mature data at higher dose levels beyond what we presented just a couple of months ago in January. We would also want to share comparative data between weekly and every 3-week dosing. We think the latter is especially relevant for our ambition to go into earlier lines. Also a clearer picture, obviously, on dose response relationships, additional insights into the safety profile at higher doses and, of course, also PSA responses. So once we have all that for 500 and for 5818, we will be sharing it, of course, either through a medical congress or through a more focused investor event. So as soon as we are ready, we will do so. Your second question, Gena, related to Alnylam. So Alnylam made their decision to opt out of the profit-sharing arrangement before our most recent HBV functional cure data was available. As you know, that data is only going to be presented for the first time on Friday at EASL on May 9. So this decision was really based on their own strategic portfolio prioritization.

Your next question comes from the line of Paul Choi with Goldman Sachs.

I want to ask about -- first about EASL and it looks like you have a late breaker of the doublet in combination with the Virion 200 asset. Just curious, I think that's the first look we'll get at that program. And so just curious sort of what the rationale is behind that new triplet combination strategy there and just sort of how you think about the development plans for that versus your other combinations? And my second question is, can you comment maybe in broad strokes on how you're thinking about completing enrollment or completing either the ECLIPSE1 or ECLIPSE-2 studies. This will be helpful to understand in the context of your cash guidance runway to 2027 since you're just putting in first patient in the first quarter here? Just some context on that timing would be helpful.

Thank you, Paul. So maybe the first question on the Virion combination. Mark, do you want to answer that?

Yes. So thanks, Paul, for the questions. I mean, first of all, that's a study conducted by Virion and we did provide access to tobevibart and elebsiran for that study. But we're not -- it's being run by Virion and it's in their portfolio and not ours. So I think the data are interesting in terms of some of the early responses in terms of surface antigen decline but that's really in their portfolio rather than ours. You're asking a really good question about HDV and our time lines. We did announced first patient dosed for ECLIPSE-1 and we have a study estimated completion date of the end of 2026. So that means we would be aiming to complete enrollment in that study by the end of this year. I mean that's an aggressive target but we are putting all of our resources behind getting these ECLIPSE trials up and running. For ECLIPSE-2, we haven't provided guidance yet but I can assure you that we are laser-focused on getting that study up and running. It's important to note that the ECLIPSE-2 actually has a 24-week endpoint. So even though it's starting dosing a little bit later, it will have a 24 versus 48-week readout. So the timing will provide some more guidance when we're able to do that but that's an important point to consider.

Your next question comes from the line of Mike Ulz with Morgan Stanley.

This is Avi Novak [ph] on the line for Mike. So a competitor of yours recently shared updated data from its TCE PSMA targeting program in metastatic CRPC. So I was wondering if you had any updated thoughts on your -- on the competitive positioning of AR-5500? And do you see a median PFS of around 7.5 months as, I guess, a fair and achievable benchmark for your program?

So yes, I can take that question. First of all, we're actually very encouraged about the continued progress for T-cell engagers in general, including the fact that JANX continues to prove proof-of-concept that masking technology actually extends the therapeutic index. And while I can't comment directly on how we would be compared, because we are relatively earlier in our dose escalation compared to where they are, we do think that we are quite differentiated in that our PRO-XTEN is a dual mask technology. It's quite a different masking technology than the other masks that are out there. It's a universal mask. It's the only clinically validated mask in terms of having clinical validation in other platforms such as the drug Altuvia, a hemophilia drug. And we do think that we have a really very favorable safety profile. We demonstrated in our January update that we have a very low rate of CRS. We do not use any prophylactic steroids. We know that every other T-cell engager program needs some form of prophylaxis. And despite the lack of use of corticosteroids, we have this very low-grade CRS and also no evidence of significant IL-6 elevations. And despite that, we are seeing some nice really early activity. The other big differentiator which I think is important, both for safety and is in the front line is that we have a longer half-life of 8 to 10 days which enables our Q3 week dosing schedule. We know that for convenience and quality of life in the frontline setting for prostate cancer, in particular, these types of differentiation is going to be critically important for overall tolerability, a huge unmet need where we think these drugs could potentially offer significant convenience for that.

The next question comes from the line of Eric Joseph with JPMorgan.

This is Ron [ph] on for Eric. I wanted to ask how does the recent bulevirtide update impact your thinking around the potential finite versus long-term chronic treatment with the combination for HDV?

Sure. Mark, do you want to take for the question?

So I think your question is about bulevirtide and their long-term outcome data and their ability to achieve finite treatment, how does that affect our program? So we -- just to remind everybody, I mean, we achieved in our SOLSTICE study very high rates of target not detected or complete viral suppression. We're achieving it in the majority of patients by week 24 and week 36. And we're getting to 64% at week 36. So that compares to bulevirtide in week 48 of only 12%. So we think we can achieve very high rates of viral suppression in terms of long-term suppression. Gilead, the bulevirtide data that are related to finite treatment are with their higher dose. So that's one thing to consider. And it's not really something that's in their label right now. So we are aiming for a chronic viral suppressive regimen. We think we can suppress the virus in the vast majority of patients. We're also achieving 3 log declines in hepatitis B surface antigen, again, just pointing to the potency and the depth and breadth of our viral suppression for delta. So we're really excited to be moving into the Phase III program.

Your next question comes from the line of Roanna Ruiz with Leerink Partners.

This is Nick Gasic on for Roanna. Maybe first on HBV. How should we think about your expectations heading into the 24-week off-treatment data for March at EASL? What are you hoping to see from a functional cure standpoint relative to the end of treatment data we got at AASLD? And maybe what implications could this new data have for potential partnership discussions in HBV?

Go ahead, Mark. No, go ahead.

So I was just going to say we are looking forward to presentation of our March data, 24-week off-treatment data this Friday at EASL. This will be the look at our functional cure rate. As you might imagine, we are going into a quiet period because it is just a very short period between now and then. So we don't want to comment extensively except to say that we have been signaled in the past that we're looking for 20% in the doublet and a 30% functional cure rate in the triplet. But I think stay tuned and you'll see the full data at EASL in just a couple of days.

Yes. The only thing I would add is that, as we have already mentioned, in January, any further development on the HBV program is contingent on securing a worldwide development and commercialization partner.

Your next question comes from the line of Phil Nadeau with TD Cowen.

Two from us. First, on 5500, you mentioned that there have been multiple doses tested since the data in January. We're wondering if you would care to comment on whether those additional doses have continued to suggest a dose response in efficacy in terms of PSA response rate and durability. That's the first question. And then second, on HDV, the RNA positive figures that you gave for the prevalence of the condition, can you clarify, are those overall prevalence or patients diagnosed having positive RNA? And if it's not diagnosed, do you have a sense of what the diagnosis rate is? Yes. Thank you, Phil. Maybe I'll start with your last question on delta prevalence. So what we did is we really looked across all available studies, all available reports on delta prevalence. And we sort of started out with determining that based on all the numbers we could get our hands on, that there are about 2 million patients in U.S. that are HPV positive. And again, through a very extensive literature search talking to KOLs, different sources, we found that on average, about 4.7% of those B patients are delta antibody positive. And again, then further drilling down, so that gives you about 92,000 patients actually in the United States. But if you then think about the patients that are actually going to get treated, those are the patients that are RNA positive that are actively viremic. And so again, based on a lot of sources, we came to the conclusion, as we shared that about 61,000 patients in the United States would be RNA positive and eligible for treatment for our regimen. So that's sort of the breakdown of how we got to the numbers. And then your first question related to 5,500 dosing, maybe, Mika, you can comment.

Yes. We have continued the dose escalation, both at the Q week and the Q3 week dosing. But really, we are not prepared to make any comments. We are encouraged with the 5818 data that also showed a nice dose response. We have that one patient who clearly had a dose response within that -- while he intra-patient dose escalated, a colorectal cancer patient who went from 60 micrograms per kg up to 600 micrograms per kg and continue to have a long durability of response lasting over 18 months. But just sit tight and hopefully, we'll be able to say something soon.

Your next question comes from the line of Alec Stranahan with Bank of America.

This is Matthew [ph] on for Alec here. Maybe a couple from us on 5525. We saw recently that the trial design on clin trials for 5525 includes 4 parts: monotherapy escalation/expansion and then combos with pembro escalation/expansion. Would be helpful to have any color on why you chose this design, maybe the ordering of the parts and whether you would still explore combination options if initial monotherapy data looks good.

So yes, I'm happy to answer that. Thank you for the question. Yes, we're very excited about having our third PRO-XTEN T-cell engager program go into the clinic. We believe we've shown some nice early proof of concept with the prior 2 molecules. And in terms of the trial design, we do know that there's good scientific rationale for combining with a checkpoint inhibitor. What we've seen with prior T-cell engagers is that you can see upregulation of PD-L1 upon treatment with the T-cell engager. And so it really makes sense in terms of combining with a checkpoint inhibitor as well with combinations, again, in the context of other T-cell engagers, is that we've seen deeper responses and more durable responses with the combination. Hence, we are considering the combination for the 5525 program as well. And as you mentioned, there are 4 parts. The first part is dose escalation as monotherapy. The second part is to look at specific indications in expansion cohorts as monotherapy and then Parts 3 and 4 is similar except in combination, a dose escalation component with pembrolizumab followed by an expansion cohort with combination at, again, a data-driven decision on which combination -- which indications that we would pursue.

Your next question comes from the line of Patrick Trucchio with H.C. Wainwright.

Patrick, we cannot hear you.

Just the first question is on the CHB program. I'm wondering if you can tell us in terms of the functional cure rates that you're looking for, would you be looking for those rates in kind of certain levels of HB surface antigen at baseline? And separately, I'm wondering on the HDV program, do you need data from all the ECLIPSE trials in order to submit for regulatory approval? Or how should we think about potential for accelerated approval? Is that a possibility? And then just the last question is just in terms of partnering or collaborations, how should we think about both the CHB program but as well any of the PRO-XTEN programs? And in particular, is there 7 additional programs in preclinical development.

Yes. Thank you, Patrick, for that question. Maybe I'll ask Mark first to address your questions on the hepatitis B and delta programs.

Sure. Thanks for the question. So for the MARCH Phase II study in chronic hepatitis B, as we presented at AASLD, we saw the best responses at end of treatment in those patients with surface antigen levels at baseline of less than 1,000. This is very consistent with what others are seeing with different mechanisms of action in the field that patients with low surface antigen at baseline are responding better than patients who have surface antigens that are very elevated at baseline. So we will present the data, both all comers and divided by surface antigen as we did for the end of treatment data for the functional cure data in 2 days. So look forward to that. For your HDV question, your question was, do we need all 3 ECLIPSE studies for approval. I do not believe so. I believe we need ECLIPSE-1 and ECLIPSE-2 as our base case for a filing package that should be sufficient for approval. We would be looking for an accelerated approval based on in ECLIPSE-1, the composite of target not detected in ALT normalization and for ECLIPSE-2, target not detected at virologic end point. Of course, we have breakthrough therapy designation in the U.S. and we have Prime in Europe as well as orphan in Europe. So we are in active dialogue with regulators globally about the program, how to accelerate the program and how to get this drug combination to patients as quickly as possible because the unmet need is so high. Just one other comment about partnering and I'll turn it back to Marianne is for hepatitis B, as we've said, that we are only going to be able to move hepatitis B forward if we have a global development and commercialization partner, whereas for hepatitis delta, we are in full study start-up mode for all 3 ECLIPSE studies and we are running those studies as Vir Biotechnology on our own.

Thank you, Mark. And I would just add related to your question on partnering of the preclinical programs, Patrick. I mean what is really unique is that the universal nature of the PRO-XTEN platform allows us to come up very efficiently with new potential therapeutic molecules, right which are going to be, from a T-cell engager perspective, very well engineered because that's a capability we've had here at Vir for a very long time and we can now combine it really with that masking capability. So the 7 preclinical programs that we are -- that we have started, it will be -- we envision a mix of approaches. Some of them will be kept for internal development on a number of select really high-priority targets that align well with our strategic focus. And some are open to partnerships and especially those where we think there could be complementary expertise elsewhere. So it's going to be really a mix of both strategies.

Your next question comes from the line of Joseph Stringer with Needham & Company.

Just given some of your recent work updating your HDV patient estimates, I had a question on HDV diagnosis. Have there been any changes to U.S. guidelines? And I suppose, do you anticipate any updates to this in the near term? And how big of an impact could this be to the potentially addressable patient population in the U.S.?

Thank you for that question. No changes yet to the guidelines for delta diagnosis or reflex testing here in the United States. We do believe that there is a heightened awareness also in the context of the American Association of Liver Diseases. So we are hopeful that we will continue to have that conversation, obviously and that when we have AASLD coming up later in the year that there might be some announcements in that regard. But thus far, no changes on reflex testing. That is, however, very effectively already deployed in Europe. And they are really seeing that if you just base diagnosis based on risk factors, et cetera, you're really not finding the patients. It's really only when patients are tested for hepatitis B and when they are found to be positive, they're automatically tested for delta that you end up identifying many more patients. Mark, anything to add there from your perspective?

No, I think you captured it very well, Marianne. Just to state that we do believe that the prevalence of diagnosed HDV or delta is underestimated because of the lack of reflex testing in the United States. I think once we have our therapy approved and on the market, assuming success that we would expect with such an effective product that this will drive more diagnosis and more disease prevalence. I think there's other examples of similar cases like this in medicine. But to your point, we're still not seeing the reflex testing deployed in the United States at this time.

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