Welcome to TD Cowen's 46th Annual Healthcare Conference. I'm Phil Nadeau, one of Cowen's biotech analysts. It's my pleasure to moderate a fireside chat with Vir Biotechnology. We have Marianne De Backer here with us. She's the CEO. Marianne, we'll start with VIR-5500. Congrats on the data disclosed last week and the announcement of the partnership with Astellas. Maybe we could begin by reviewing those developments. The data were quite impressive in terms of PSA reduction rates, RECIST ORR and safety. Can you briefly review the highlights of the data for those less familiar?
Sure. Hey, Phil. Nice to be here. Yes, the data are very compelling profile for the drug. Exactly what we were hoping to see. Sort of promising the potential of the platform, the PRO-XTEN masking platform. We saw, you know, very compelling efficacy combined with a very positive safety and tolerability profile. This was a trial in very, very sick patients. You know, 95% had pre-taxane, four median lines of therapy, failed on everything. They had the population, 45% had visceral mets. Really, you know, the soft tissues invaded, 80% liver mets. You know, patients with liver mets typically only have a prognosis for survival of 10-14 months. Very, very sick patients.
Despite all that, really, you know, phenomenal efficacy and safety profile, and as I said, exactly what we were looking for to show with the PRO-XTEN masking technology.
What were the PSA rates in terms of PSA50, PSA90, PSA99, and the RECIST response rates?
In the population of efficacious dose above 3,000 micrograms per kilogram, we saw a PSA50 rate of 82%, very significant. PSA90 rates of 53% and PSA99s of 29, one in three patients, and again, in a very, very sick patient population. We were lucky actually that we could determine RECIST responses in 11 patients, there we saw a 45% ORR. Again, very impressive data for this patient set.
What about the safety profile? I think for the class, there's a lot of focus on safety. How did Vir's safety data look?
Going back to what are we trying to solve for, right? T-cell engagers, again, phenomenal modality. You're basically activating the patient's own T-cells to fight the cancer. You don't need to take them out, modify it and place them back. You're really in situ activating T-cells. The problem with T-cell engagers in solid tumors has always been that you couldn't really push the dose after to, up to the efficacious levels because of toxicity. What we are doing is we are masking the T-cell engager, so it remains intact in the bloodstream, and only when it reaches the tumor, the masks are being cleaved off by the proteases in the tumor, and then it becomes active. When it's active and unmasked, it has a very short half-life, while when it's circulating in the bloodstream, still masked, it has a long half-life.
That allows us to really push the dose up to levels that are high so that we can really reach that efficacy that we're looking for, and then combined with a very positive safety profile. We also, except for a very small cohort of three patients, did not use prophylactic steroids, no anti-IL-6, so we really were able to achieve this profile without the prophylactic treatments.
I think the most prominent question we've received from investors following the data release were on durability of the responses. What is Vir's impression of the durability of the responses, and what gives you confidence that they could be durable?
I think the technology really makes a difference. Again, obviously, you know, durability has been shown with other T-cell engagers in the space for targeting other targets, you know, STIP1, KLK2. There's no reason why PSMA target wouldn't be able to show durability, but the problem has really been that you weren't able to get to push the dose high enough to get there. We believe that with our dual masking of both CD3 and PSMA, we can push to those high levels of efficacy combined with great safety, and that gives you really good prospects for durability. What we saw is a great concordance between PSA responses, so dPSA responses, great concordance with RECIST responses, and also great concordance with PSMA PET reduction.
Again, that really shows that you're targeting the PSMA, you know, you're doing exactly what you had intended biologically. We think that that bodes really well. The other thing I would say is our data set is still early. However, Johann de Bono discussed a couple of cases in our call last Monday, and he actually reiterated those at ASCO GU last Thursday, where you can see 12-month durability, eight months durability in patients, again, who have failed on five prior lines of therapy, you know, sometimes on treatment for again, over a year. You sort of can see the early signs of us achieving that kind of durability.
What are the next steps for the program? When could we see another update? We always want more.
Yes, I know. I know. We just, you know, delivered the update last Monday. The first question was, "When's the next update?" Anyhow, the good news is that again, we secured this partnership with Astellas. I'm sure that we're gonna talk more about it. We have selected a go-forward dose. It will be a every 3-week dosing, and we are ready to start our expansion cohorts the next quarter. That has been fully aligned with Astellas. We will be going into an expansion cohort late-line monotherapy. We will also be going early line in combination with enzalutamide, and then we will be starting an expansion cohort in metastatic hormone-sensitive prostate cancer, again, in combination. All that's lined up, and we expect to enter pivotal trials in the course of next year.
In those studies, or those expansion cohorts, will you be using prophylactic steroids, or are you still not gonna do that?
That is not the plan. I mean, we have shown that we really didn't need it to achieve a really good therapeutic index. Of course, you know, we could also always explore things more going forward, but it will not be part of our expansion cohorts now.
Great. We're all aware of other TCEs in development, particularly in prostate cancer. How would you assess the competitive landscape? Where does VIR-5500 fit into the treatment or into the landscape?
There is a number of different T-cell engager for prostate cancer targeting different tumor-associated antigens. Some have shown great efficacy, but with a rather problematic toxicity profile. Some have shown great safety, but with, you know, a rather mediocre efficacy profile. If you look at what we have shown, and again, it's an early data set, but it's really that, you know, Goldilocks type of profile where you achieve great efficacy, but it's combined with very favorable safety. Again, not using prophylactic steroids, not using any other prophylactic medicines that patients would need to take. It's every three weeks, so quite convenient, allows us to move to earlier settings, outpatient. We think that we have a potential best-in-class TCE for prostate cancer.
Do you have an opinion on what level of efficacy compared to what level of safety CRS ICANS would need to produce to be viable? What type of PSA response, what type of resistance response against how what toxicity profile would be viable?
Yeah. I mean, if you're targeting the outpatient setting as we certainly are, you wouldn't want to see a lot of, you know, grade 3 CRS, for example. We are not seeing any grade 3 CRS in our go-forward dosing cohorts. We also seeing very little grade 2 CRS, we have a very favorable profile to make that possible.
Great. Maybe turning to the Astellas partnership, congratulations on also getting that done last week. Really busy week. What makes Astellas the right partner?
Yeah. Last year, as we saw the profile of VIR-5500 developing and, you know, started to look more and more positive, we thought it was really important given the competitive landscape that we were able to move very fast and that we were going to be able to do much more indication and signal seeking in parallel. We thought that, you know, with a partner, a very experienced partner in the prostate cancer space, we would be able to do that. We ran a competitive strategic process. We hired a bank to help us do that. We talked to a lot of strategics, and in the end, we selected Astellas because they had a very aligned point of view on, again, speed to market. We wanted to, you know, keep very involved in the program.
We strongly believe in the program, a 50/50 profit split deal was essential for us. Again, Astellas has done these kind of deals with Seagen. They have done it with Medivation. Very aligned from a structural deal perspective, but also from, as I said, speed to market, what needs to happen, you know, doing a lot of things in parallel at risk. I think it's really a great partnership for us.
What does the partnership mean for Vir? How does it change your strategy or your direction?
Again, it allows us to retain very significant value, very significant involvement in the program, while at the same time, you know, again, allowing us to accelerate and do more things in parallel. What it also does because of the R&D cost share, you know, we take 40% of the global development cost share, it allows us to free up, you know, cash to potentially invest and ungate some of our other programs, which of course, you know, depending on our data, is gonna be very important.
You referenced the 40% development cost share. Could you go into more detail about the exact terms in terms of upfront, cost sharing, back-end revenue sharing?
First, there's three very important components. One is there is a $1.7 billion total in milestones, upfront and milestones in the deal. There is a 50/50 profit split in the U.S., ex-U.S., you know, we get royalties on sales. We also have a co-promotion option in the U.S., which is important as we are certainly planning to build our own commercial presence in oncology in the U.S. The $1.7 billion in milestones and upfront, you can divide into $240 million of cash upfront. There are $75 million in equity with a 50% premium, there's a smaller $20 million manufacturing milestone, which is, you know, going to hit, you know, by mid-next year.
Perfect. In terms of strategy, who controls the development of 5500? Is there a steering committee? Is it Astellas? What say does Vir have in the strategy?
Yes. We have a very favorable governance mechanism across the board. We have a joint development committee, joint manufacturing committee, joint commercial committee, joint steering committee, and so on. Very much joint governance where we have equal representation, and we make decisions jointly. There's a level of escalation sort of depending on what happens, but again, we'll be jointly deciding on when data are going to be released, et cetera. We think that it's actually very favorable for us.
You obviously obtained these assets from Sanofi. How does Sanofi's or your existing relationship with Sanofi impact the terms with Astellas? In particular, how much of the economics does Sanofi share?
We entered into the Sanofi deal back in... It closed in September 2024. We paid $100 million upfront, $75 million milestone for our EGFR program, and then, you know, around $434 million in milestones across all the programs, and then, you know, certain amount of royalties. What is happening here in addition is that we pay 20% of certain proceeds that are coming our way from the Astellas collaboration. We have detailed it all in our 10-K, and that is basically because we are within a 2-year term from the start of the collaboration.
Got it. Okay. Moving to the rest of the TC pipeline, I guess first, broadly, can you outline that pipeline for those less familiar? Second, how does the success that you've had with VIR-5500 read through to those other candidates?
Sure. We licensed three clinical stage assets from Sanofi. One is our PSMA program. The others are our HER2 program, VIR-5818, and then EGFR, which is VIR-5525. They're both in Phase I. We also licensed a masking technology, so the platform for the entire field of oncology and infectious disease. That has allowed us to progress seven preclinical assets in oncology quite swiftly. We have, you know, now in total 10 programs that use the PRO-XTEN technology. That, you know, is, you know, it's really a plug-and-play platform, so it's exactly the same mask across all of these programs, which again allows us to move quite swiftly. It's also the same mask that is being used in ALTUVIIIO, which is a drug that Sanofi has on the market. Again, there's a lot of read-through, you know, across these different programs.
The fact that VIR-5500 has shown, you know, really has proven the technology, you know, the hypothesis on paper is really being proven by the profile we're seeing. That bodes really well for sort of the read-through to our other programs.
For 5818 in the HER2, remind us of the data that's been presented and what have you got it in terms of the next data release?
Yeah. We presented data in January of last year. It was still a very early data set. We showed, you know, 33% ORR in a metastatic CRC population, again, a small subset. We will be sharing data both on the monotherapy and the combination with pembrolizumab in the second half of this year.
At one point you had, I don't want to say committed, but suggested that you were gonna move forward in colorectal cancer. Is that still the plan?
Yeah, we will be sharing together with our data also, our plans, our next plans, our next steps for, you know, expansion cohorts.
Got it. What's 5525, what's the status there? When could we see initial data?
Yeah. We started dosing 5525 in July of last year. Everything is going really well. Again, as soon as we have a meaningful data set on EGFR, we will be sharing that. We're exploring it in head and neck, non-small cell lung cancer, CRC. Yeah. Again, everything is going really well, but the data isn't mature yet.
Great. maybe moving to HDV in the, in the last 10 minutes or so, can you provide an overview of the data that you've shared for, tobevibart and elebsiran in, HDV, and what are the key takeaways?
Sure. Yeah. For people not familiar, hepatitis delta is a rather severe disease. People that are co-infected with hepatitis B and hepatitis delta progress to liver cirrhosis, you know, potential hepatocellular carcinoma, liver transplant quite quickly. It's a very serious disease, and there's nothing available here in the U.S. to treat patients. We have a combination of an antibody and an siRNA, tobevibart and elebsiran. We showed some new data earlier this year, which showed that if we treat patients for 96 weeks on this regimen, we achieve 88% target not detected. That means that almost nine out of ten patients, you entirely get rid of the virus, so the virus can no longer be detected in the blood of the patients. That's very significant because, again, hepatitis delta is a very small RNA virus you really want...
It's the cause of the disease, and you want to get rid of it. That was very, very impactful. We are running our registrational trials, consists of three parts. Two of our trials have fully enrolled. One is still being enrolled, and everything is going really, really well. We expect data to read out, first data to read out fourth quarter of this year. The next data set, the first quarter of next year.
Can you remind us of the primary endpoints of those studies?
Yeah. We have an ECLIPSE trial, which is basically, patients are being treated with our regimen compared to a deferred treatment. It's almost like a placebo-controlled trial. The endpoint there is TND plus, ALT, normalization after 48 weeks. The second trial is looking at patients that fail on bulevirtide, which is Gilead's drug, and that are being switched over to our regimen. There the endpoint is just TND after 24 weeks. The third trial, ECLIPSE-3, is really combining head-to-head our regimen with bulevirtide. Again, there the target is, the endpoint is TND after 48 weeks.
There's some debate, at least among investors, as to what is the best endpoint in HDV, whether it's target not detected or, target not detected plus ALT normalization. What's Vir's opinion on how we should interpret the different efficacy measures?
Yeah, I mean, as we talk to a lot of KOLs, obviously, as I mentioned, the disease is caused by a virus. Getting rid of the virus is sort of your number one priority. We do that really in a very superior way. We have actually compared our own antibody to bevacizumab as a monotherapy compared to the combination of an antibody and a siRNA, so our regimen that we're taking forward in registrational studies, and it's a marked difference. I mean, we can, you know, reach maybe 40%-50% TND with the antibody alone, but we can get, as I mentioned, up to 90% with the combination.
If you look at HBsAg levels and how much we can reduce them, I mean, again, very high levels with our combination, but only about, you know, 10%, 20% with the antibody alone. We do think that this dual mechanism is incredibly powerful. You know, again, the more you can get rid of the virus, the more you can expect healthy outcomes for patients. On the ALT side, I mean, we measure ALT, we don't really see a difference between a monotherapy antibody and the combination, so that doesn't really make a difference.
How would you size the market opportunity? How many patients? What type of pricing is possible?
Sure, yes. As we've said, we expect about 60,000 patients in the U.S. that are actively viremic, so patients that, you know, should seek treatment, and approximately double that in Europe. It's very similar to, you know, what, for example, Gilead has reported. What the price is concerned, you know, prices are actually very, very high in Europe, you know, compared to many others, and that's because, again, it's an orphan disease, it's an orphan liver disease. Prices in Europe vary somewhere between EUR 60,000-EUR 150,000. For here in the United States, you know, we have not put out specific pricing, but brokers have put prices, you know, between $150K-$250K, so that gives you some frame of reference.
How would you assess the competitive landscape in HDV?
Yeah. You have bulevirtide on the market in Europe, will get to the market in U.S. We think that's a really good thing because it will create much more awareness around the disease. From an efficacy perspective, as I mentioned, after 48 weeks, we achieve about 66% target not detected. Bulevirtide achieves about 12% target not detected. Bulevirtide is a daily injection. We are monthly, two injections every month. Patients can administer it at home, or it can be administered elsewhere. You know, we think we have a very favorable profile.
How well diagnosed are the 60,000 patients? Are they mostly known to the medical community, or is there still some patient finding that has to happen?
No, the estimation is that at this point, only about 15% of those patients are actually diagnosed. Again, you know, it doesn't happen because there's nothing available to treat patients, but there's a lot of, a lot of learnings from Europe where, you know, they introduce reflex testing, so everyone who tests positive for B, you know, gets tested for hepatitis delta, and that has significantly increased diagnosis. That's not the case yet here in United States, but that could be the promise.
Great. maybe moving to some general corporate questions to finish up. In terms of your cash balance, can you remind us what your cash balance is pro forma post the Astellas deal, and how long your cash is gonna fund operations?
Our cash balance that through the end of the year was $783 million. With the Astellas deal, we have extended our cash runway into the second quarter of 2028. Last week we also did an equity raise, and we raised $173 million, so that obviously is also going to be deployed actively towards our T-cell engager portfolio.
Great. With your now healthy cash balance and some of the responsibilities, offloaded to Astellas, how do you think about the other assets that you have in terms of internal development versus partnering?
That is really a decision we make on an asset-by-asset basis. Certainly we want to keep a healthy set of assets wholly owned and others we will partner. What we have found, for example, for our preclinical assets is that the progression is very, very quickly. We have a team that is very good at coming up with, you know, active protein therapeutics, you know, T-cell engagers in this case, and the combination with the plug-and-play mask has gone, you know, exceedingly well. We now have seven programs that are progressing very, very fast. For sure, we are going to partner a number of our preclinical programs. Again, it's gonna be a mix of keeping things internally versus, you know, finding partners.
And by what criteria do you evaluate whether you want it internally versus externally? Is it size of development program versus size of end market, or?
Yeah, it's, you know, size of the opportunity, it's the competitive landscape, it's the size of the funding that would be required to bring something fully to market. Also sometimes capability, right? If it's something that really requires a specific capability and the competitive space is very intense, then of course you make a different decision.
Great. You've answered all my questions. Anything I should have asked you that I didn't that you think it's important investors should know about Vir?
I think it was very complete. We are extremely excited about the data. I think it's really a proof point, not just for VIR-5500, but for the entire platform and sort of puts an exclamation mark on our on our strategic pivot as a company to immune oncology.
Great. Well, thank you for coming to the conference.
Really appreciate it. Thank you.