Thanks for coming and joining us at the Leerink Global Healthcare Conference. My name is Roanna Ruiz. I'm one of the senior biotech analysts here at Leerink, and it is my pleasure to welcome Vir Biotechnology here with us today. I have CEO Marianne De Backer. Thanks so much for joining me.
Yes, a pleasure, Roanna.
I'm really looking forward to diving in. I'll start with a bigger picture question just to kick it off. For investors that are digging into the story, could you just recap some of the strategies that you're focusing on, both on infectious disease and in oncology, and how has the company evolved over time, especially over the recent past year?
Sure. Happy to, really great to be here at the Leerink conference. The premise of Vir Biotechnology is that we really try to harness the power of the human immune system to to fight disease, and we do that both in infectious disease and in oncology. In oncology, about 18 months ago, actually, we set sort of forward a vision of developing masked T-cell engagers to treat metastatic solid tumors. Since then, we now have three clinical stage programs. We just reported very compelling data two weeks ago on our prostate cancer program, but we also have two other clinical stage programs, a HER2 program that can be deployed across, you know, a large potential set of indications and also an EGFR program where again, we're really exploring a lot of different indications in solid tumors.
We have a registrational program ongoing in hepatitis delta, so with initial data reading out actually already towards the end of this year.
Yep. There's a lot going on. I'll start on the oncology side since you had that recent data readout for VIR-5500, the PSMA-TCE. With that data, and it was presented at ASCO GU as well, could you just highlight some of the key takeaways from there that you think are most important for investors to think about?
Sure. This was data from our monotherapy dose escalation phase I of VIR-5500 in the late-stage population with metastatic prostate cancer. It's important to point out that the subset of patients that we actually show data in were very sick patients, so nearly all of them had had taxanes. Most of them had had four prior lines of therapy that they evolved on. You know, a lot of patients, 45%, had visceral mets, and 18%, so almost one in five, also had liver mets. Of course, prognosis in these kind of patients is very low. While the general metastatic prostate cancer population has sort of a 30% survival, you know, post 5 years, for patients with liver mets, that's, you know, 10-14 months. Very very sick patients in our trial.
I think that's an important sort of first premise to talk about. Looking at our data, and you can see here one of our case studies, it was really phenomenal to see the response rates. Here is a patient that, a 63-year-old male that had very extensive liver mets, and as I just pointed out, patients with liver mets are the ones with the worst prognosis. This patient had 40 lesions just in the liver alone, and you can see after treating with VIR-5500 only nine weeks later, you can see a total obliteration of all those metastatic lesions, PSA of 99. You can also see very nice concordance with radiographic efficacy measures. We saw a number of these patients, again, very sick patients, very advanced with very impressive efficacy.
Overall, we have been able to select a data set of patients that were treated with a dose above 3,000 micrograms per kilogram. If you look at that data set, we achieve 53% PSA 90s and patients like this, one in three patients also PSA 99s.
Yep.
You know, very significant efficacy, and importantly, because we have a masked T-cell engager combined with a very promising tolerability and safety.
Yep. Leaning into this, how do these data so far shape your confidence in VIR-5500 just differentiating against the competitive landscape in PSMA and some of your competitors in the pipeline?
Sure. If you think about it, what we were really trying to do, our T-cell engager, which binds PSMA and CD3 T-cells, our T-cell engager is masked with hydrophilic polypeptides on both tumor-associated antigen side and the CD3 side, so it's a dual mask. The whole hypothesis is that this masked T-cell engager will circulate in the blood of a patient, and nothing will happen until it reaches a tumor microenvironment. At that point, the high levels of proteases in the tumor will cleave off the protease linkers in our molecule. The masks will drop off. The T-cell engager really gets exposed. It's gonna bind the tumor, bind the T-cells, and there's gonna be cancer cell-directed T-cell killing.
That premise, that was sort of the theoretical premise, and we had shown some preclinical data and early clinical data before that, you know, showed you that that could actually be working. With the data that we show now on VIR-5500, you see that in action really very beautifully. First of all, on the safety side, so we could show very low levels of CRS, which is typically, you know, systemic immune activation is typically a big problem for T-cell engagers. It's the reason why T-cell engagers in solid tumors have really not shown a lot of success. We could show very limited CRS, mostly grade one, just some fever. We could also show very low levels of PSMA-specific, but off-tumor toxicity.
You know, hypolacrimation, dry mouth, all these things, very low levels, very low incidence, and also very low levels of really treatment-related AEs. That showed you that the safety profile was quite exceptional for a T-cell engager, and again, combined with very good PSA levels, so 82% above 3,000 of PSA 50, 53% PSA 90s, and twenty-nine percent PSA 99. That really with good concordance with RECIST. We'd have 11 patients that were RECIST evaluable. We showed a 45% ORR, and also great concordance with PSMA PET. That combination of, again, dose-dependent antitumor activity and very tolerable safe profile of our masked T-cell engager was exactly what we hoped to see.
We have this one case study of, I think it's patient case number four in our investor deck, where you can see not just that this is working, you know, when looking at PSMA PET and seeing the lesions disappear, but here on the left-hand side, you can also see these are biopsies from the patient. It's a lymph node biopsy, and you can see on baseline, you know, the brown is sort of the PSMA staining, so really the tumor. Then you can see after only week five of treatment, so that's basically four dosages of our drug, you can see that, you know, the PSMA lesions are really disappearing, and the pink cells here are the T-cells that are really infiltrating. So it's exactly what you would expect from the mechanism of action of the platform.
Yep. Got it. How are you thinking about where VIR-5500 fits into earlier lines of therapy, potentially versus later lines? This is something that some investors have asked me, like, could you talk a bit more about, you know, motivation to go to pursue hormone-sensitive setting as well? Just like walk us through the thought process there.
Sure. Yeah. Obviously, initially, we are studying VIR-5500 in very late line patients, and we think there's tremendous potential there, and we'll obviously continue to do so. We have already last year in October, however, also started combination with enzalutamide, going into earlier line patients. The way that the profile of our drug is shaping up, and again, of course, it's early data, but the way it's shaping up is we can dose every three weeks, which is really great for positioning in an outpatient setting. We have a safety profile, but as I mentioned, very limited CRS, again, greatly fit for an outpatient setting. The safety of the drug also allows it to be combined with a lot of different other modalities, potentially. It opens up really a broad area of things that we could explore.
What we have been discussing with our partner Astellas is our initial focus, and again, this could broaden, but our initial focus is, you know, speed is of the essence. We're pursuing late line monotherapy. We're going to start expansion cohorts already the second quarter of this year. We're going to explore combinations in metastatic CRPC, but also earlier line, as mentioned. Then hormone sensitive, we think. I mean, it's gonna potentially take a little longer, but we think is another group of patients where there is actually a lot of need for something that, you know, could really be very efficacious and very safe at the same time.
What we also have noticed, and again, it's very early days, we only had seven patients post radioligand therapy in our trial, and unfortunately, four of them were only treated at very low doses of VIR-5500. We showed this one case, it was actually the one that I just showed, case study four, where post-actinium treatment, so post an RLT, we could still show very compelling efficacy. We have two more patients that have efficacious dose of VIR-5500 that are going to read out. We think the potential of both pre-Pluvicto and post-Pluvicto or any other RLT is really also a possibility for VIR-5500.
Yeah. That's interesting. I'm glad you mentioned Astellas 'cause that was also part of the news that came out recently.
Right
in terms of announcing your new partner. For any investors that are newer to the story, could you recap the highlights of the deal and the terms and the partnership going forward with Astellas?
Sure. Yeah. Very excited about partnering with the world's leader in the prostate cancer field. With Xtandi, you know, they have the leading drug in prostate cancer, and they have 3 to 1.5 million men across the world. They have incredible experience in the field, very excited to be partnering with them. What was very important for us is to enter into a 50-50 profit split deal in the U.S., and have a co-promote in the U.S. because our ambition over time is to become a commercial company also in oncology, and that, you know, gives us a good foot in the door. It's a very attractive deal in the sense that it's a co-development, co-commercialization. The governance is very robust. Decision-making is with equal representation, joint decision-making in everything.
We have joint steering committee, joint development committee, joint manufacturing committee, so we do a lot of things jointly. From the perspective of alignment on vision for development, we have exactly the same ambition to move to market very, very quickly and to do things in parallel. Not sequentially sort of testing things, but really doing a lot of things in parallel and really trying to explore the full potential of the asset. Then financially very attractive terms. Overall $1.7 billion in milestones and royalties. As I mentioned, a 50/50 profit split in the U.S. and then royalties on sales ex-U.S. It also takes a lot of costs away from our P&L. I mean, we are gonna be responsible for about 40% of the global development costs, while Astellas will take on 60%.
Yep. Got it.
Mm-hmm.
You mentioned moving quickly and then doing things in parallel, just being a little bit more efficient there. Anything you can share about the timeline or possible design features that you're thinking about down the road eventually for a pivotal phase 3 for VIR-5500?
Yes. Mentioned for our three selected areas, going late-line monotherapy, early line combination, for mCRPC, and then also for early line and hormone sensitive prostate cancer in combination. We are going to start expansion cohort second quarter. That will allow us, our ambition is to actually skip phase I and to go into pivotal trials already next year. Yeah, we are very excited to move very swiftly. We have selected our go forward dose. It will be in every 3-week dosing. And again, we will be sharing more information what exactly that dose is at a later time.
Yep. Yep. Interesting.
Mm-hmm.
One question that I've gotten from investors a couple times, a little bit more specific in thinking about the swimmer plot that you presented for VIR-5500. Could you highlight some of the main takeaways there, and any caveats or things to consider from that data so far? I know it's still maturing, still evolving and, you know, how could that update, you know, and improve or, you know, change in the future when you have another sort of data update for VIR-5500?
Sure. Yeah. The swimmer plot showed you 17 patients that were PSA evaluable, of which 11 were RECIST evaluable. It basically shows you very nicely that first of all, the dots that you saw on there, yellow and orange, it shows you that the CRS that we are seeing, as mentioned before, is very limited and mostly happens really at the early onset of dosing. You don't sort of see it down the road. It also showed you that you know, there was great concordance of PSA responses with the partial responses and the complete responses, some four out of five which were confirmed. Of course, it's an early data set.
We have a couple of patients that are post six months, and we had, you know, RECIST responses that were confirmed post 27 weeks, but still sort of an evolving data set for sure.
Yep.
Yeah.
I hear you.
Certainly more to come there, over time.
Yep. I know 5,500 is not the only thing you're working on, so I'm gonna shift gears.
Yeah
A little bit to some of the other oncology programs. I'll start with the HER2 masked TCE, that's 5818. I know in the past you've talked about metastatic colorectal cancer and other cancers in terms of compelling indications to go after. What early signals are informing that view, and how are you thinking about it going forward?
Yeah, maybe to remind everyone. First of all, the HER2 program and also our other program in the clinic, EGFR, they all use the same PRO-XTEN masking technology. The HER2 program is also HER2 CD3. It's also dual mask, and it has exactly the same PRO-XTEN hydrophilic polypeptide chain there. The early data that we showed on the HER2 program at January of last year basically showed you some initial signs of activity. It shows that I think it was in concentrations above 400 micrograms per kilogram, that about 50% of the patients showed tumor shrinkage. As a reminder, the HER2 program is very different from the prostate cancer program in the sense that it was a basket trial.
We had really patients with all sorts of tumors, gastric, CRC, breast. I mean, really the whole gamut of potential, sort of very heterogeneous, you know, subset of patients with, you know, very different tumors. In that data set, we could show that about 50% of the patients showed tumor shrinkage. Coincidentally, we had a very small subset of at least six patients with CRC, metastatic colorectal cancer. Of those, we could show two that had a confirmed partial response. 2. That was two out of six. Again, that was a very small data set. It should have showed you the similar initial signs of efficacy combined with a really good safety profile. Again, it's a basket trial. The monotherapy dose escalation weekly Q3W has been completed.
We are still dose escalating in combination with pembrolizumab. What we have announced is that we will share data in the second half of this year on the program.
Yeah. Interesting. For that upcoming dose escalation data in second half of this year, how would you frame expectations for investors for that readout? Like, what should they be thinking about on efficacy, safety, any dosing parameters that you hope to see in that readout?
Yeah, I would really see it, as I mentioned, given it's a basket trial design, a lot of heterogeneity, that it's a signal-seeking trial. You're trying to see in what indications, you know, would it be making most sense to do potential expansion trials. We will be able to share, you know, efficacy, safety, you know, get some clarity on that signal seeking and also on potential next steps for the program.
Yep. Wanted to ask a little bit about your other TCE, the EGFR.
Right.
That's VIR-5525. I know that's also progressing through dose escalation, including a pembrolizumab combination arm, I believe. Could you talk about how you're thinking about that program? I know you have a competitor also with an EGFR. Could you just frame what is exciting you about your program?
Yeah. I mean, our EGFR program, and again, EGFR is an example of course, a tumor-associated antigen, but it's also widely expressed in healthy tissues. It's sort of, you know, a real test to masking technology, I would say, generally. But we have decided to explore it initially in four indications. That's what's ongoing in our monotherapy and our combination trial. We only started at, you know, very low dose, obviously, in July of last year. Everything is going really well. The dose escalation is ongoing. We are again exploring Q week and Q three week. A bit early to say when we will have sort of sufficient data to share with the public.
Yeah, I mean, obviously we will be making quite a bit of progress in the course of this year on that program.
Okay. Got it. I know you're working away as well on at least, I think seven is the count, other masked TCEs in preclinical development. There's a lot going on. How are you thinking about this portfolio of like, in terms of prioritizing it and moving some of these different assets forward into the clinic?
Yeah. One thing I have been really amazed about is how because the platform is really a plug-and-play technology, how quickly you can really design new masked T-cell engagers. We have a very experienced team that has worked, you know, their entire careers on generating protein therapeutics, antibody therapeutics, which is a great synergy with now the technologists that we have brought in from Sanofi, who, you know, have worked their entire careers, you know, decades on masking technology. We're really bringing that together, and these programs evolve very, very quickly. It's just too much for us to handle. I mean, it's a phenomenal platform. It can really create a lot of value for the company, but absolutely, we will need to partner some of these programs.
We are very thoughtful about what programs do we want to keep and fully pull forward ourselves versus the ones that you know we are going to be partnering. There's quite a number of ongoing conversations in that regard.
Yep. Got it. I'm gonna flip gears to the hepatitis delta program as well, and with tobevibart and elebsiran. Maybe just zooming out a little bit, how do you think about the competitive landscape in Delta virus so far in terms of next generation approaches, how your combination regimen fits in, and, you know, how are you thinking about the unmet need there as well?
Yes. Very happy to see that there is certainly an increased awareness for the disease. At least that's what we are feeling in a lot of the conversations. I think the fact that Gilead is going to launch in the space, there's another competitor, I think is creating more interest in understanding what Delta really is, and it's a very severe disease. It's the most severe form of viral hepatitis. There's nothing available on the US market for the disease, and we absolutely feel we have the most compelling offer to make to patients. We have a dual regimen consisting of an antibody and an siRNA. We're really attacking the virus in two different ways. By doing that, we're really being able to get patients to undetectable very swiftly.
We had already shown earlier that after 48 weeks of treatment, we could get about 66% of the patients to undetectable. You know, just a couple of weeks ago, we showed data, early data from our SOLSTICE trial that after 96 weeks of treatment, basically nine out of ten patients, we can get to undetectable, so you can no longer detect the virus in the blood of patients. That's an amazing level of efficacy, and it's combined with a very favorable safety profile. We're very happy with that profile. We think it's an absolute winning profile for the future. We're working really hard to getting initial top-line data out fourth quarter of this year, and then further top-line data first quarter of next year. The program is progressing incredibly well.
Again, I think it's really good thing for patients that there is more attention to the disease. Hopefully that will have impact on diagnosis of the disease. Again, history teaches us that once there is a regimen available for patients, even if the initial one isn't sort of the best one, it sort of, you know, acts as a flywheel. It creates awareness. There's more diagnosis, and patients get treated in the end.
Yep. Interesting. You mentioned the recent SOLSTICE data out to 96 weeks. Can you just frame in terms of the target not detected results and also ALT normalization results? Like, what's been the feedback from physicians absorbing that data and, you know, what's most exciting to them out of all the results?
Yeah, I mean, physicians know very well that obviously the disease is caused by the virus, and if you can get rid of the virus, that's sort of, you know, the ultimate what you would want to see. So the reactions are really phenomenal. I think it's also the reason why our ECLIPSE 1 and our ECLIPSE 3 trials have enrolled, you know, at incredible speed and also ECLIPSE 2 is enrolling really well. So yeah, there's great enthusiasm from key opinion leaders, and they're really very convinced that not just, you know, the target not detected being so differentiating. We have been comparing what does an antibody alone or tobevibart do compare to combining the dual regimen tobevibart with elebsiran, so combining an antibody with an siRNA. There's just this incredible difference in reaching target not detected.
There's also an incredible difference in how much you can reduce the HBsAg level, which is a protein that delta needs for its life cycle, so that there's a difference between 20% for an antibody alone and 80% for the combination. This all bodes incredibly well for the outcome for patients.
Yep. Super exciting. I know you mentioned Gilead's going to launch bulevirtide in the US.
Correct.
Assuming that goes forward, et cetera, like how do you see the hepatitis delta market evolving from here? Like where would physicians want to, you know, pick and choose different regimens, assuming everything goes well and you also launch in the U.S. and, you know, how would they want to think about treatment sequencing or is that even the right paradigm to think about for delta virus?
Yeah, I would assume that patients will want to give the best regimen to patients. Of course, initially that is not gonna be available. Gilead has announced that they will launch bulevirtide. It's a daily injection that patients need to give themselves. After 48 weeks of treatment, the TND that Gilead achieved was about 12%. It's markedly different from what the data we have shown and that I just discussed. Again, after 48 weeks, we achieved 66% of TND, and we have a monthly regimen. It's two injections every month that either patients can, you know, inject themselves or they, you know, they can have it done by physicians. But I think from an efficacy and a convenience perspective, we think we have a very differentiated profile.
Again, the expectation is that physicians will want the best regimen for their patients.
Yep. Got it. Maybe a couple quick questions, just zooming out again. How are you thinking about cash runway going forward and expectations there and spending between oncology versus infectious disease and pushing all these programs forward?
Yeah. Since December, we have actually markedly increased our cash position. We have entered into a partnership with Norgine for our European rights to the Delta program. We have obviously, as discussed, entered into the Astellas collaboration that is expected to close early April. We also have done a financing most recently. We have cash runway until the second quarter of 2028. We are in a really good position. Again, of course, with Delta and the prostate cancer program, we have sort of our two key priorities, but it also offers us perspective to explore and ungate some other programs that we have in the clinic.
Okay. Great. Wrapping it up, a final question I like to ask. What do you think the market still underappreciates most about Vir's story today?
Yeah. We're really a turnaround story, right? We used to be a Covid company, very successful. But of course, you know, variants came, and that all disappeared and Vir Bio had to really reinvent itself. We have really done so. We set out that vision to become an immuno-oncology company also about 18 months ago. I think with the VIR-5500 data, that's a phenomenal proof point of that vision of being able to use masking technology and masked T-cell engager to really fundamentally potentially change care in a solid tumor. We think that we are in a really good way, and we have tremendous opportunity with the platform.
Yep. Great. Well, thanks so much, Marianne, for stopping by, and really great discussion.
Yeah. Thank you, Roanna.
Thank you.
Appreciate it. Thank you.