Good morning, everyone. My name is Cory Kasimov, one of the senior biotech analysts here at Evercore. It's my pleasure to host our next discussion with Vir Biotechnology. Fortunate to have CEO Marianne D. De Backer here with us. So, Marianne, thank you very much for being here. First question I'm starting with for everybody is kind of, as the year comes to an end, shockingly enough, just love to hear kind of you reflect on the year that was and talk about Vir's biggest accomplishments to date so far.
Okay, great. Yeah, thank you, Cory, and thank you, Evercore, for hosting us here at Vir Biotechnology. Yeah, I mean, looking back at 2025, it was really a year of tremendous, I would say, focused and flawless execution on our clinical programs. So, obviously, we made a lot of advancement on our three clinical stage T cell engagers. And then we have our registration program for hepatitis delta. So, you know, if you look at the accomplishments of this year, so it sort of started in January where, for the first time, we reported data on two of our masked T cell engager programs. Vir-5500, a PSMA CD3 T cell engager, and then Vir-5818, our HER2 CD3 T cell engager. And in both of them, we saw promising early results.
So, as you know, we are very committed now to providing an update on Vir-5500, our PSMA program in the first quarter. That was a very important milestone after doing the deal with Sanofi the year before, sort of late in the year before. At the same time, this year, we have opened up a cohort to explore Vir-5500 in combination with ARPIs in first line MCRPC. Again, an important milestone where we have moved from just exploring the molecule in late line to now also really looking at early line patients. Then finally, in our oncology portfolio, we also dosed the first patient in phase 1 in July for our EGFR T cell engager program. Again, quite a heavy lift on the clinical side this year. That was not all. As you know, we have also our hepatitis program.
Just very recently, we read out the 48-week data on our Hepatitis Delta program, phase two, Solstice, where we showed really transformative data. 66% of the patients get rid of their virus. No longer the target can be detected after 48 weeks of treatment. That was an important accomplishment for our team and really gave us a lot of confidence for our phase three program in Delta. That phase three program is now fully enrolling. We recently announced we have completed enrollment for Eclipse one two months ahead of schedule. We are really on track for Eclipse two and Eclipse three enrollment, and we will be able to come with a complete data set for Eclipse in the first quarter of 2027.
Okay.
So quite a heavy lift this year.
Yeah, there's a lot going on. So we're going to dig into a lot of what you just talked about. We'll not surprisingly start with the prostate cancer program, so 5500. And maybe remind us of how you think this is differentiated from other PSMA-based approaches, in particular as it relates to other masked bispecifics.
Yeah, so maybe start with the basics. So why is masking important, right? For our target PSMA Vir-5500, if you would dose a naked PSMA T cell engager to patients, you would basically not be able to do that, right? It would be too toxic. And on the one hand, you know that PSMA is a fantastic target and it works, and biologically there's a lot of confidence around the target. On the other hand, the modality of T cell engagers, it just doesn't work with a naked molecule. So you have to look at masking. So our masking technology is quite unique. First of all, it's always dual masked. So we have masking of the T cell engager both on the tumor-associated antigen side, so on the PSMA side, and also on the CD3 side. And we do think that is important.
And then secondly, the nature of our mask is quite unique. So basically, our mask, our Xtend mask, is this hydrophilic polypeptide that forms sort of a shell around the T cell engager. And there's, again, two masks, one on the CD3 side, one on the PSMA side, and it forms this shield around the T cell engager. And because the Xtend masks are protease cleavable, the Vir-5500 molecule really only gets activated in the tumor microenvironment where you have these high levels of proteases that can cleave up the masks, release the T cell engager in its active form that can then form the synapse with the T cell and with the cancer cell and induce cell-directed killing. What is also really unique about our platform and about the Xtend masks is that the Xtend masks by itself provide actually for a half-life extension.
That's actually the origin of the masks. Initially, they were used as half-life extenders. And so what it does, the two masks on Vir-5500, they extend the half-life to somewhere between eight and 10 days. So that really allows us, and that's exactly what we're doing in our clinical trials, to explore longer duration of timing intervals for dosing. So it allows us to explore every three-week dosing. And again, importantly, from a safety perspective, is that once the T cell engager Vir-5500 gets unmasked, the half-life is really short. It's a matter of hours. So again, it provides that protection when you need it. If your T cell engager is in the bloodstream of patients, nothing happens, gets to the tumor environment, it gets cleaved, it's active, but then really gets released through a kidney, et cetera, very quickly and efficiently.
And then finally, it is important to know that the Xtend masks, Vir-5500 or Vir-5818, this is sort of not the first rodeo for Xtend. So there's a drug on the market, Altuvio, that Sanofi markets that has three Xtend masks, has been shown to be very, very safe and is now approaching blockbuster status. So the combination of all that gives us a lot of confidence around our masking platform.
Do you need both masks to be removed in order to engage the tumor and induce a response?
Yeah, so what needs to happen is, obviously, you need to be able to create a synapse between the CD3 and the T cell and the T cell engager with the tumor-associated antigen, in this case, PSMA. So you need cleavage of both of the masks to really achieve that activity.
Okay. And then I guess with the preclinical data that you have, the initial clinical data that you've seen, how confident are you that both masks are being removed appropriately? I mean, is there ways to accurately measure that?
Yeah, I mean, again, we have done a lot of preclinical work, both in vitro and in vivo where we can study it. But I think the most important data that you can really look at is our clinical data, right? We have now two programs in which, again, unless you unmask, you wouldn't see activity. And we have, again, earlier this year showed both in our HER2 program, especially in CRC patients, very clear activity showing that the hypothesis of unmasking works. And similarly, in our PSMA program, we have shown these early signs of activity through PSA biomarker measurements that, again, show that unmasking happens and it really does not just give you the efficacy, but it allows you to achieve efficacy with a combination of a much better safety profile.
Yeah, so on that front, when we think back to the initial data cut last January, I guess, one of the things that stood out to us was the activity that you had coinciding with the low rates of CRS. So how important of a finding is that in this patient with this kind of drug profile, but in this patient population?
Yeah, I mean, again, generally, what has been holding T cell engagers back in application for solid tumors is the fact that you have these very high-grade CRS. And so it has been impossible to really deploy T cell engagers often because of that reason, or at least fully exploit the potential of T cell engagers in the field. And so what the masking allows you to do is to get to a much better therapeutic index and allow you to, because of the safety, allow you to dose up much higher and as a result, achieve much better efficacy. And our data in January, again, it was early data, but it showed that in 12 patients which were at efficacious dose ranges, we saw about 58% of the patients showing a PSA of 50, and then about 8% of the patients showing a PSA of 90.
And that was associated with only 25% of the patients showing any CRS, and everything was below grade two. So this is, again, this is like the hypothesis really of the masking platform that we want to prove that you can get to much better efficacy with associated acceptable safety. It's really that therapeutic index that you are exploring through masking.
Right, okay. So you just alluded to the promising PSA responses that you saw in that last data cut. Obviously, at the end of the day, what ultimately matters here is going to be durability. Can you provide some color as to why you don't intend to provide radiographic PFS or overall survival at this next readout?
Yes, I mean, we're all absolutely committed to showing that data at the time when we have it, right? I think it's important to realize that our phase 1 data at this moment in time is still dose escalating. And so you need a certain period of time post-dose to measure, of course, our PFS. And we're still at a time where we're dose escalating, and the cohorts in every dose are relatively small. Absolutely, we will be in a position to do that at some point, but for our next data cut in January, it will be more focused on looking at the earlier readouts that you can do, obviously PSA, durability of PSA, and so on.
All right, makes sense. All right, so I will say upfront, I recognize that this is a difficult question to answer, but I'm going to ask it anyway. It's very safe to say your pending first quarter update is going to be comped to the JANX data. So I'm curious what you made of their update. I guess this was on Monday of this week. And maybe easier part to answer is what are some of the nuances that folks should be on the lookout for when they're trying to do those dreaded cross-trial comparisons?
Thank you, Cory.
Set you up properly.
Yes, so first of all, just again, to the core of the problem we're trying to solve through masking, it's really to get to better therapeutic index. And again, I think what JANX is showing, and they have a single mask, what they have showed through their data over time is that, again, you cannot give a naked PSMA T cell engager to patients. You can give a single mask T cell engager to patients, achieve efficacy. And of course, there's debate about what that safety looks like. But it's a really good, in our mind, a really good proof of mechanism that masking can get you there on the journey to achieving that optimal therapeutic index. And then again, as it relates to differentiation with our program, again, our Vir-5500 molecule, it's dual masks. It's a totally different kind of masking.
It's the really steric hindrance type of masking. We have the long half-life of the drug that is provided by the Xtend mask that will allow us to explore this every three-week dosing and who knows, perhaps even less frequent in the future. So there's all these differences. And again, the Xtend mask has been shown to be very safe in other molecules that are marketed. So we think we have a lot of things that are very differentiated, and we're really looking forward to sharing our data.
Okay, and we're looking forward to seeing it. I guess last question on the pending data. So if we're not going to see the durability data yet, because understandably, it's not ready yet, what can we expect to learn in the first quarter? How many patients, how many doses are you going to be talking about, the amount of follow-up that's there? Can you just kind of sort of little preview of what we could expect to see?
Yes, certainly it's going to be a meaningful data set. You will see data exploring both weekly dosing, every three-week dosing. The data that we're going to share is going to be limited to our monotherapy dose escalation in late-line patients. As I mentioned, we're also exploring first line in combination with ARPI. That data will not be mature yet at that point in time. But for the data set in late-line patients with our monotherapy dose escalation, you will see all the safety data, obviously CRS, all the other AE events. You will see efficacy data measured by PSA, PSA 50s, PSA 90s, durability of that response. We will have RECIST data. So it will really be a, we will have evaluation of dose response. So taken together, I think it will be a really meaningful data set.
Again, we will also share sort of how we think about that data set in the context of the next steps for the program.
Okay, perfect, so final question on prostate cancer is kind of bigger picture one, and it's where you think bispecifics could ultimately slot into the treatment paradigm. Is the goal here to have, I mean, hard to say, but better efficacy than Pluvicto? Should we think of this more in the post-Pluvicto setting? Where do you think if things go as you hope they can go and anticipate they'll go, where does this slot in?
Yeah, so theoretically, Vir-5500 could play both pre and post-Pluvicto. And of course, the data will have to sort of show that over time. Also, I think if you look at T cell engagers in the prostate cancer space, typically what patients have or are seeing now as options, not on the market, but often still in clinical trials even, is either great efficacy, but very problematic safety, or they see good safety given high-dose steroids that are administered, but then maybe only modest efficacy. So we're really trying to find that sweet spot where you can have great efficacy combined with very acceptable safety. And again, if you have such a profile, then you can get to duration of treatment, you can get to dosing schedules of, for example, every three weeks. You can start thinking about treatment in outpatient settings.
You can start thinking because of the safety of the combination of the treatment around combinations. So it really offers up a lot of avenues to explore, but we really want to be guided by our data.
Right, okay, makes sense. All right, so in the final few minutes that we have left here, do you want to switch over to your Hepatitis Delta program? We saw updated data at AASLD where efficacy deepened with additional follow-up, plus there was a New England Journal publication. So, curious what the early feedback has been like from the medical community post all of this.
Yeah, feedback has been actually tremendous. I mean, for people, KOLs in the field, they understand the tremendous unmet medical need and how quickly these patients really progress to cirrhosis, need liver transplants and so on. So they see this as very, very meaningful. This is actually the very first time in the past. Often both KOLs and regulators were looking at a combination of virological response and, for example, ALT. They had to really do that because the treatments that were available, and again, there aren't that many, there's nothing in the U.S., there's Bulevirtide in Europe, did not allow you to really get to target not detected. They did not allow, or they only allowed in a small subset of patients to really get rid of the virus.
What we have seen now with our data, as mentioned, is that after just 48 weeks of treatment, and it's an every month injection, two injections, you can get 66% of the patients to target not detected. You see the same level of efficacy in cirrhotic and non-cirrhotic patients. You also see that the HBsAg level that the virus needs for its replication cycle, we can reduce that with our regimen four logs down. That is considerably more than what you can achieve with an antibody alone. Sort of the totality of the data investigators and KOLs are very enthusiastic about. I think it's also apparent actually from the enrollment in our Eclipse trials. Again, Eclipse 1 enrolled two months ahead of schedule. We're seeing very, very positive enrollment rates across the board.
Yeah, I was going to ask about that. I mean, do you take the pace of that enrollment as a sign of the underlying demand for therapy in this setting?
Certainly the patients are there. And secondly, the strength of our Solstice data is really helping us. I would say the two other factors is we have obviously long-standing relationships with KOLs and investigators in the field. They have been following this program over a long period of time. And then finally, I would say we also have a phenomenal clinical operations group that is really on this to get the trial enrolled as swiftly as possible.
And then just very quickly, what kind of product presentation do you anticipate having when this ultimately comes to market in terms of, is this an at-home auto injector? Is it a prefilled syringe?
Yeah, so it's going to be two subcu injections, and it will offer the flexibility for either the patient to administer at home, him or herself, or have it administered by a physician in hospital.
Okay, excellent. Well, we had more time to go further into this, but we're all out of time. So Marianne, thank you very much for being here and good luck with the upcoming data.
Okay, excellent. Thank you, Cory.