Vir Biotechnology, Inc. (VIR) Earnings Call Transcript & Summary

Thanks for joining day 2 of the 2025 Bank of America Healthcare Conference. My name is Alec Stranahan. I'm senior biotech analyst covering Vir at Bank of America. And I'm very pleased to be joined by Marianne De Backer, Chief Executive Officer of Vir. Thanks for being here, Marianne.

Yes, my pleasure.

Yes. Looking forward to the conversation. So maybe we'll just jump right in and maybe at a high level, you've got 2 strategic focuses for the company currently. Maybe you can walk us through what those are and sort of the path forward over the next 6 to 12 months for the company.

Sure. Yes. Thank you, Alec, and thank you for hosting us as Vir Biotechnology. We are really pleased to be here. So we are very excited about our clinical stage pipeline, which, as you said, is covering sort of 2 main areas. But what is really underpinning all the programs is really using the human immune system to fight disease. And in one case, it's to fight an infection and in the other case, it's to fight cancer. So our most advanced program is rare and orphan liver disease caused by a small virus called hepatitis delta. And that program is in registrational trials. We have dosed the first patient in the first quarter of this year. And that, again, it's a disease where there's a high unmet medical need. There's no treatments available here in the United States, and we have shown really very compelling data in our Phase II SOLSTICE data. So I'm sure we'll talk about that more. Then the other part of our pipeline is a series of masked T-cell engagers for metastatic solid tumors. So we have a HER2 program and a PSMA program. They're both in Phase I dose escalation. And we shared again some early but quite compelling data in January of this year on both programs. For the HER2 program, it's a basket trial in a lot of different tumors, but very compelling data showing 50% tumor shrinkage across the board and then 33% confirmed partial responses in colorectal cancer, very advanced sort of last resort patients. And in our PSMA trial, we showed early data in January showing that all patients that were dosed above 120 milligrams per kilogram showed a PSA response. 58% showed a PSA50 response and we also showed a PSA90 response. So this was very early but quite compelling data with really great safety profiles. And what is coming next is we have just put on clinicaltrials.gov more information about our trial design for our third clinical stage program, which is targeting EGFR. And we are intending to dose the first patient in the first quarter. So a lot going on in our clinical stage portfolio. And if we have time, we can talk a bit more also about our preclinical pipeline.

Okay. Great. Yes. Maybe we can run down the list one by one, maybe starting with hepatitis. HDV, the ECLIPSE programs, I saw that the first patient was dosed in those trials. Maybe speak to enrollment to date and sort of what we should expect from the data.

Yes. So maybe just to set the scene. So what we are trying to do in hepatitis delta is really come up with a chronic treatment. So it would be something that patients that are so unfortunate to be having an active viremic disease are treated with our regimen, which is a combination of an antibody and an siRNA. So we're sort of attacking the virus in two different ways. And we're also aiming to activate the immune system to clear the infection. And so the data we showed in our SOLSTICE trial, which was our Phase II trial was really compelling in the sense that we could show that 64% of the patients were getting rid of the virus entirely, no delta virus detectable in the blood anymore after only 36 weeks of treatment. So that was very compelling data and was sort of the basis upon which we designed our ECLIPSE trial for registration. And our registrational program is really consisting of 3 trials, ECLIPSE-1, 2 and 3. ECLIPSE-1 is really there for patients that are really naive, have not been treated with anything. Those would typically be patients, for example, here in the United States because there's no treatment available for delta here. And so it's a trial design that basically gives patients either a regimen from the start or there's a 12-week deferred treatment. So it's, in essence, a placebo-controlled trial that is reading out after 48 weeks, and then we're looking at target not detected, so no longer delta virus available -- detectable in the blood combined with normalization of ALT. So that's the first trial. The second one is ECLIPSE-2 and ECLIPSE-2 is really there for patients that actually have access to the only drug that is currently available for delta, and that's bulevirtide. And for patients that are not achieving good protection against the disease on bulevirtide, they are put on this trial, and it's basically a switch trial that allows them to then be put on our regimen. And of course, we are going to show their head-to-head versus bulevirtide switch. That endpoint is just target not detected. It just looks as -- are you getting rid of the virus. And the endpoint is also already after 24 weeks. So the combination of ECLIPSE-1 and ECLIPSE-2 is really what we believe is going to be sufficient for pursuing registration for both United States and Europe. And we are, depending on how the data look in ECLIPSE-1, going to see if even based on ECLIPSE-1, there would be this possibility. And then the third trial, ECLIPSE-3 is really only there to do a bulevirtide head-to-head trial and to really have the data showing superiority, very important for pricing and reimbursement in Europe. So for ECLIPSE-1, as we mentioned, the first patient was dosed in the first quarter, that was earlier than anticipated. We have also now shared that we expect the primary completion date for ECLIPSE-1 to be December of 2026. And we also expect enrollment to be completed this year. So we are going as fast as we possibly can on ECLIPSE-1 and everything is in progress for ECLIPSE-2 and 3.

I guess how does the different standard of care between the U.S. and EU influence your expectations around pace of enrollment in ECLIPSE -1 versus ECLIPSE-2? And then we can get into the -- maybe the endpoints.

Yes. So as we said, in the United States, there's really no treatment available for patients. So -- and patients that have a co-infection of hepatitis B and delta and viremic, they really progress to extensive liver disease very quickly. It's a very severe disease. Half of the patients actually progress to mortality because of the infection with delta. So we estimate that there's actually going to be a high number of patients that really have no other options. And so we -- in the start-up of our ECLIPSE-1 trial have seen that certainly, there's a high engagement from KOLs and PIs to be involved in the trial. But similarly, I mean, if you think about ECLIPSE-2 trial, which is really gated towards areas where bulevirtide is available, such as Europe, for patients that are not achieving good viral suppression on bulevirtide, again, those patients are typically already quite advanced in their disease. They are cirrhotic. So there's a high urgency also there to really find a solution. And we have shown in our SOLSTICE II trial that we actually see really good results both in non-cirrhotic and cirrhotic patients, [ CPTA ]. So also there, we think there's going to be a high likelihood for physicians to want to see their patients treated. But it's not just from a physician perspective. I mean if you're a patient, of course, here in the U.S., there's just nothing else. And if you're a patient in Europe, the only other option that is available to you is bulevirtide. It's a daily injection. It's a chronic treatment. You have to reconstitute the drug. And the target not detected that has been reported to be achieved after 48 weeks is only 12%. So again, I think there's a high likelihood both from the perspective of physicians, but also from the perspective of patients that they would want to be on our regimen because ours is a monthly dosing 2 injections, again, with target not detected rates that are quite superior, at least in our Phase II trial.

Okay. And I think you've also adopted that sort of 48-week time point in ECLIPSE -1. I believe it's 24 weeks in ECLIPSE -2. I guess, maybe talk about -- is that more just ethical since there is an approved other option?

Yes. I mean, so the patients on ECLIPSE -2 have already been on bulevirtide, right? So they had been on bulevirtide for a while, again, they have not been adequately controlled on bulevirtide. So there's really no need to progress the endpoint beyond 24 weeks. And of course, that was a discussion with the regulators. And this is actually coming together very nicely because ECLIPSE-1, again, readout after 48 weeks, ECLIPSE -2 after 24 weeks. ECLIPSE -2 is starting a little later, but it has the potential to come together very nicely from a timing perspective. Again, we estimate primary completion date for ECLIPSE-1 at the end of next year.

And I know screening has been a concern within HDV for a while. As you're thinking about a potential commercial launch, any work you're doing to maybe help increase awareness of the disease or thinking about this in the context of accelerating enrollment in your clinical studies?

Yes. So for sure, the diagnosis rate in the U.S. is really low. And there's a lot that we can learn here in the U.S. actually from what has been happening in Europe. So in Europe, because the treatment became available, even one that might not be so great from an efficacy and convenience perspective, it has triggered quite a lot of discussion around diagnosis of delta. And in some countries, reflex testing is now in the guidelines. So patients that are tested positive for hepatitis B, the same blood sample is being used to test them for hepatitis delta antibodies. And again, that's the starting point for them getting to be tested for delta RNA and really finding those patients that have active viremic disease. And what has been seen, for example, in countries like Spain is that once they amended the guidelines to reflex testing that they were identifying many more patients than what physicians would have otherwise done based on just identifying risk factors. So what we really need to get to here also in the U.S. is getting reflex testing in the guidelines. It's, of course, very difficult in a market like the United States, even if you diagnose patients today, there's nothing to treat them with. So we really think there's going to be a bit of this flywheel effect that once you really demonstrate with this great regimen coming with very high target not detected rates in the chronic treatment that there's going to be an impetus to really test. And so we are working a lot with KOLs, with patient advocacy groups to see that, I mean, there's an update to the guidelines that there's going to be increased awareness. I think the Hepatitis B Foundation has recently, actually, I think, 2 weeks ago, put out a study where they surveyed a lot of different stakeholders in the hepatitis B space to see who knows about delta, and there's clearly a lot of awareness building to be done. And so we are fully aware of that. The really good news is that, again, we have tried to identify where are the patients, the delta patients in the United States, which is the market we want to focus on. And patients seem to be really concentrated in metropolitan areas. So that makes it a palatable disease for us to go after. And from a commercial perspective, the resources you put to it, et cetera, is really manageable. At the same time, we have announced last week during our earnings, Alec, that we are going to seek a partner for delta ex U.S. because we think it's probably going to be very beneficial to have a party that is already with boots on the ground in Europe, has ideally experience in liver disease or rare liver disease and can take this on without us having to spend a lot of resources on building that commercial infrastructure.

That makes sense. And I guess the last question I have on HDV, and I want to leave enough time to talk about your TCE platform as well. Have you had any initial conversations with payers in the U.S. or in the EU around sort of what kind of cost-benefit analysis could be done? Or are there any kind of pricing analogs that you may be considering?

Yes. So I mean, first, obvious pricing analog you can think of at least in Europe is bulevirtide, right? I mean, and pricing of bulevirtide varies in Europe, somewhere between list prices, $80,000 and $150,000. Again, we have orphan drug designation for our delta regimen. It's recognized as a rare disease, rare liver disease caused by a virus. So the prices are sort of commensurate with that determination. And you can imagine that prices in the United States are typically higher. We have also worked with an external agency looking at analogs. And so we have looked at analogs of diseases that are similarly having a high unmet medical need, there's no other treatments available at this moment in time, et cetera. And the analogs that we have found, and I think we are going to share a little bit more information about that in the future, clearly demonstrate that this could be a very significant opportunity even for the U.S. alone.

And I guess maybe last question on HDV is more of a -- and obviously, this is a moving target and things are changing. But you mentioned it is a rare disease. We've heard some positive comments around rare disease and sort of this kind of approach from [ Makary ]. Any change in your FDA interactions since the changing of the guards or -- and I guess, any change to your approach in terms of clinical development?

No, not really. I mean what is really incredibly beneficial is that we have breakthrough designation. So our interactions with the agency, with the FDA is very smooth, and we have seen absolutely no change actually. So thus far, it's all going really well as planned.

Okay. Okay. That's encouraging. Maybe flipping over to the TCE platform, saw some pretty encouraging early data last year or earlier this year, I should say. Maybe at a high level, any comments on the data that we've seen to date and any sort of points of differentiation just at a high level for the platform, and then we can get into the individual assets.

Sure. Yes. So maybe just to start indeed with the platform. So the PRO-XTEN platform, the masking platform that we have is really unique in the sense that it's a true plug-and-play platform. So we use the same masks across all of our programs. So we have 3 clinical stage programs. They have exactly the same mask. And we also shared last week that we have started working on 7 preclinical programs. Again, the same PRO-XTEN mask can be deployed on all of these programs. So that is very unique. I mean it's obviously -- it's very efficient to be able to not having to design your mask every time from scratch, but to be able to take something that is really working. And you also really learn from every program. I mean the first program that the team started on with HER2, they started at a very low dose, 1 microgram per kilogram, dose escalated very slowly. There was a lot to learn. But now both the regulators and the PIs have seen how the mask behaves. They have a lot of confidence in it. The other thing is that the PRO-XTEN mask, I mean, it's a hydrophilic mask. And if you look at an AlphaFold depiction of it, you can have your T-cell engager that is binding tumor-associated antigen on the one hand and your T-cell on the other hand. And it's really like this globe around it that is protecting it from obviously binding to the target and to T-cells. And it's also protecting because it's hydrophilic and amorphic, it's protecting you from potential ADAs. So -- and the fact that the same XTEN mask has been used in a marketed drug, ALTUVIIIO, gives us a lot of confidence that this is very safe. This has been in a lot of patients. And obviously, it's -- ALTUVIIIO now is almost a blockbuster drug by Sanofi. So what we have seen with the platform thus far is that we can achieve a very good therapeutic index, so we can achieve efficacy but with much better safety. So the mask is really staying on in circulation in the blood. Nothing is happening. But when the masked T-cell engager enters the tumor microenvironment, then the protease cleavable linkers that are on it and that have been designed to be really cleaved by proteases that have high activity in the tumor are being cleaved, the T-cell engager is then becoming active and can exert its effect and tumor cell killing. What is also very unique about the platform is that the XTEN masks themselves extend the half-life. I mean that's where the name comes from XTEN. So we have a half-life of our HER2 program of about 5 to 6 days. We have a half-life of our PSMA program of 8 to 10 days. And what this allows us also to do is to think about the different dosing schedule. So -- and in both of our programs where we have already shared data on, we are exploring not just weekly dosing, but also every 3-week dosing, which would be, of course, very relevant as you want to move into early lines of therapy.

Right, right. And you are considering PD-1 combinations with your HER2 that would be a great fit with PD-1s, which are also every 3-week dosing.

Correct. Exactly.

I guess how does this maybe -- how does this form a moat around this program? Obviously, you need to see what the data looks like and how the combos react to patients. But how does that unique ability to dose every 3 weeks sort of set you up for success down the road? And are there any overlapping AEs based on the data that we've seen to date?

Yes. So we have not really disclosed our Q 3-week data yet. The only thing that we have shared is that there's one patient in our HER2 data set that we shared in January that has shown excellent safety and efficacy and was a patient that had been dosed every 3 weeks. Again, there's a number of benefits from every 3-week dosing. Obviously, as you go to earlier lines of therapy, convenience for patients is very important. To your point, when you dose with other regimens, if you can be in sync with that, that's very beneficial. So we think that's going to be potentially very impactful. And we explore that across all of our programs. So do you want to talk maybe about each program more specifically.

Yes. Yes. Maybe we could unpack the HER2 data a little bit more. HER2, I think most people think about breast cancer, but it's also expressed in other tumor types like CRC. What's sort of the opportunity in your view for this asset? Or when could we sort of get more refined guidance around which tumor types you plan to explore?

Yes. So the HER2 program was really designed as a basket trial. And so basically, any HER2-positive solid -- patient with solid tumor, third line plus was eligible to get into the trial. And so what you saw in our data in January is a high heterogeneity of tumor types. To your point, breast, but very -- a whole variety of GI cancers, so a very broad variety there. However, we had very early on in the trial, a colorectal cancer patient that had a quite dramatic response. It was a patient that was dosed at 60 micrograms per kilogram, and that showed very significant response and then was intrapatient dose escalated to 600 micrograms. And that patient had been on therapy for over 18 months, as we shared with you in January. So what that triggered is that some of the PIs seeing that example put relatively a little bit more metastatic colorectal cancer patients on the regimen. So because of that reason, we have been able to show in January that above 400 micrograms per kilogram, actually, we could see in a subset of metastatic colorectal cancer patients, 33% confirmed partial response, so very relevant. Also because these are MSS patients typically don't respond to immunotherapy. So very compelling data. And just to remind you that both for our HER2 program, but also PSMA program, these are patients that have seen a lot of lines of therapy. This one patient that I was referring to had seen 7 prior lines of therapy. So very last resort patients that really are quite desperate to get on the therapy that...

Okay. And maybe flipping to PSMA, saw some pretty robust responses across the dose escalation. Obviously, you're still dosing up. But I guess what can you say about maybe the criteria for choosing the go-forward dose? Is this solely based on the PSA reduction? Is it durability, survival? What's sort of your thought process around the [indiscernible]?

Sure. Yes. So what we showed in our PSMA program is -- it was a small subset, 12 patients. But in those 12 patients above 120 micrograms per kg. We showed that everyone was having a PSA response. As I mentioned, 58% PSA50 and then we had 1 patient that showed a PSA90 response. And we could see at whole body MRI in a patient that you were really liquefying the tumor. So very, very early compelling data and a very low grade 1, grade 2 CRS at dose levels of efficacy. So in the meantime, we have, of course, dose escalated above 1,000 micrograms per kilogram that we reported on in January. Determination of sort of our dose will be based on a couple of factors. Obviously, efficacy of PSA and other measures. We're also looking at PSMA PET. We are looking obviously at the safety profile. The determination will really be based on the therapeutic index, right? We want to achieve the best possible efficacy with the best possible safety profile and to your point, show durability down the road. The other thing that we are exploring, as I mentioned, also in this program is every 3-week dosing, which could be very relevant. And also as we think about potential combinations going forward with our regimen, we want to make sure this is as convenient as possible for patients.

Okay. Makes sense. And you mentioned your EGFR program as well entering the clinic. Anything to look out for here? I mean this has been a challenging target for others in the space, masked and unmasked. How is your approach may be different here? And what should we be thinking about in terms of cadence of this study?

Yes. So given that EGFR is obviously not just expressed in tumors, but also in a lot of normal tissues, this is sort of detest for a lot of the masking technologies. We believe, again, that our platform is very powerful and has the potential to really make a dent here. So what we are going to do is we're going to -- in a selection of EGFR-positive patients, head and neck, lung cancer and a couple of others, colorectal, we are going to do monotherapy dosing. We're going to get to see what the dose escalation looks like and then go into potential expansions there. And then we also have a combination with pembro planned. So if you look at -- again, we posted our trial design on clinicaltrials.gov. It's a combination of monotherapy, pembro and then potential escalation cohorts depending on the data we see.

That's in another basket study similar to the HER program?

Yes. Even though it's a basket, it's enriched, right? It's really enriched to, as I said, head and neck, lung, colorectal. So it's going to be more concentrated.

Okay. So indications where PD-1s are already approved and widely...

Correct. Yes, that makes a lot of sense.

Yes. Yes, I think so. Well, maybe in the last couple of minutes that we have, you've got over $1 billion in cash. I think you said runway into mid-'27. Maybe you could just touch on how you're prioritizing capital allocation. And maybe a good point to end on would just be sort of wrapping up what this runway covers in terms of the next data updates.

Sure. Yes, you're absolutely right. We have a cash balance of about $1 billion, and that takes us into mid-2027. So if you think about what it is we would have by mid-2027, obviously, we would have -- we would expect to have data on our ECLIPSE trial, so the delta readout. We would, of course, have progressed in our HER2, PSMA, EGFR program. We haven't shared sort of when we are going to put out new data on our HER2 and PSMA programs. But what we're really trying to do is get to a point where we continue to dose escalate, we generate that data, both efficacy, safety, dose response, looking at the dosing schedule, looking at durability and come out with a meaningful data set on those programs that is then going to guide us as to the next steps. So of course, all that data will be available either this year or next year. Our EGFR program, as I mentioned, is going to be first patient dosed this quarter. So that data will also develop and become much clearer. So there's a lot of data catalysts to come between now and '27.

And then you've got the preclinical side, which we didn't have time to talk about. And I know you have some interesting discovery efforts as well. So I'm assuming you'll be working on those in the background and those should come and add to the narrative.

Yes. Our capital allocation priorities are really on our clinical stage programs, right? But we have a platform now that is incredibly powerful, and we have the global rights in the field of oncology and infectious disease, and there's a lot of interest in the platform. So we're looking at partnering on preclinical programs on a number of targets that are biologically derisked where you know that a T-cell engager could actually be working, but that toxicity is really holding it back and where our masking could be a real solution.

Okay. Okay. Great. Well, I think with that, we're at time. So please join me in thanking Marianne for the really engaging discussion, and thanks for joining the conference this year. Really appreciate.

Thank you, Alec. Appreciate it.