Good morning, everyone. I'm Corey Kasimov, one of the senior biotech analysts here at Evercore ISI, and it's my pleasure to host our next discussion with Vir Biotechnology and the company's CEO, Marianne De Backer. So, Marianne, thank you very much for being here.
Thank you.
Maybe a good place to start is kind of use the recent past to help potentially inform the future. As we wrap up what's been a very busy 2024 for Vir and begin to look ahead to 2025, can you kind of provide an overview of Vir's key priorities and anticipated milestones, and maybe talk about how the recent AASLD updates have kind of shaped the focus for the company?
Wow, that's a lot of time.
Yeah, it's a lot to cover in one. We don't have a lot of time.
Yeah, no, excited to be here. Thank you for hosting Vir Biotechnology here at the Evercore ISI Conference. Yeah, so, you know, if you think about Vir Biotechnology, what we're really doing is trying to harness the power of the immune system to really drive patient impact. We do that in two areas, as you know, infectious diseases and oncology. Now, to your point, what are our milestones for 2025? They're really shaped by the recent data that we shared at AASLD. So, for hepatitis Delta, we're going to start our registrational trials in the first half of next year, which is, of course, very exciting, and we showed some really promising data, very strong, you know, virological declines and ALT normalizations in patients with Delta infection.
For hepatitis B, what is going to be important for us in the second quarter of next year is understanding what the functional cure rates are going to be. So in Delta, we're looking for chronic therapy. In B, we're really looking to achieve a functional cure. What we shared at AASLD is 48-week end-of-treatment data. Now we have to wait six months, you know, and then look after that finite amount of treatment, and then six months of therapy. What's that functional cure rate going to look like? That's then going to guide, you know, our next steps for the year. In oncology, as you know, we have entered into a very exciting partnership with Sanofi, which has given us access to three clinical-stage T-cell engagers and a platform for use in oncology and infectious disease.
And for the T-cell engagers, we recently announced that on January 8th, we will be hosting an investor event, sharing initial data on both our HER2 and our PSMA program. So, that's going to be an important catalyst. And also, in the first half of next year, we're going to start phase I, so first patient dosed with our EGFR T-cell engager program. So, a lot, a lot coming next year.
Right. So, I wasn't lying when I said there's a lot going on.
Right, there's a lot going on.
All right, so let's start talking a little bit more about Delta and the SOLSTICE data that you had that's been very well received. Can you kind of talk a little bit more about the specific advantages that you think you have here over standard of care?
Absolutely. Yeah, so, Delta is the most severe form of viral hepatitis, and patients that have Delta infection are always also infected with hepatitis B virus, so it's a dual infection. And what we have shown at AASLD is that with a combination of our antibody called tobevibart, which we have designed for immune engagement, and an siRNA, that that combination can drive down Delta RNA very, very significantly. So, we saw reductions of 41% of Delta RNA below the target of detection at already 24 weeks, and that went up to, you know, 63% at 36 weeks, and then in a rollover cohort, up to 80% target not detected at week 60. So, really exciting data where we can really drive down Delta RNA. And also, in the majority of patients, we saw really good reduction of ALTs.
All the patients that we enrolled in the trial had abnormal elevated ALTs. We are also looking at ALT normalization, and that showed in more than 50% of the patients, we saw ALT normalization, and the rest of the patients actually were all hovering sort of around that upper limit of normal of ALTs. That, you know, very promising data. What is also important beyond, you know, the efficacy, of course, is very good safety profiles, so no grade 2 ALT elevations. We have a very convenient dosing. You might know the only standard of care that is available to patients is in Europe, and it's a daily subcutaneous dosing. You know, very elaborate for patients to adhere to. Our regimen is a monthly double subcutaneous injection, so very, very convenient.
Finally, I would say what was really interesting to see is that we didn't really see a difference of activity in cirrhotics versus non-cirrhotics, and that is important because Delta patients progress to cirrhosis very quickly, and it's really important that you can show that efficacy in patients that are, you know, developing cirrhosis, so all in all, very interesting data package that led us to engage with the regulatory authorities, and as I mentioned in my introduction, we're now looking forward to starting our registrational trials in the first half of next year.
Okay, so commercially, there's clearly not a lot in the way of competition, if any. Clinically, how do you look at the competitive environment for hepatitis Delta? I know there's like BlueJay's out there, they recently had some data. You know, how differentiated is Vir's approach overall?
Right, so, you know, it's really good to see that Delta is getting more attention in general because for a while, I think we had to explain a lot about, you know, what hepatitis Delta was and how the unmet need was looking and how important it is to actually come with a new regimen to market. I think that is now dissipating, and there's, you know, more belief, and you see more, you know, entrance into the field, which is really good. But, for example, BlueJay, I think it's really important, of course, to not make comparisons because, you know, we have at times, you know, cross-trial comparisons, different endpoints, different ways to define things. To give you a couple of examples, when we speak about target not detected, we really are talking about no detectable virus anymore, really zero IUs per mL, so not amplifiable anymore.
That's in line with what the regulatory authorities are also looking for. Again, in other trials, that definition is a little bit different. Also, in our trial, we only enrolled patients, as I mentioned, with elevated abnormal ALT. Some other trials also enrolled patients with, you know, normal ALT. You know, again, important to really look at the details. We are very excited about our combination treatment because, as I mentioned, our antibody tobevibart, it's not just blocking entry of the virus into the hepatocytes, but it's also engineered for immune engagement, so to help the immune system fight infection. The siRNA is basically dicing up, you know, all the HDV RNA. Together, you know, that's a very powerful combination, and you see that very deep and fast, you know, decline of Delta RNA when you dose patients, and you see that actually really very fast.
Of course, this is virology, so in virology, you often work with combination treatments. It has a number of benefits, often, you know, better efficacy and also better resistance protection. There's a number of benefits we see with our regimen. Again, it has proven to be very safe and tolerable.
Okay, so your ECLIPSE program, there's three distinct trials there. Can you kind of provide an overview of the design and kind of the rationale behind three clinical studies?
Sure. So, what we are aiming to really do is reach patients that are at sort of different stages of potential treatment, and we're also taking into account that the geographical landscape of where treatments are currently available, standard of care is currently available, is very different from what you would typically see. So, we here are in an environment where there's a standard of care available in, for example, Europe, bulevirtide. It is not available in the United States. So, the way that we have designed our trials, ECLIPSE 1, 2, and 3, is really to accommodate that complexity and making sure that we're really going to be able to address a diversity of patient populations and then also be set up very well for not just approval, but really get an optimal pricing and reimbursement down the road.
So, ECLIPSE 1, the way that you can think about it is really looking at geographies like the United States where bulevirtide is not available, and we really compare our treatment to a deferred treatment, and we then, you know, look at 48-week post-start, you know, both the combination of target not detected, so driving down viral RNA and ALT normalization, which is your typical regulatory endpoint, so that's ECLIPSE 1. It's 120 patients, and it's a two-to-one ratio randomization, then ECLIPSE 2 is different in the sense that there we are looking at patients who actually have been exposed to bulevirtide, so typically in Europe and some other geographies, yet have not been able to achieve the outcomes that you would like to see.
So, these bulevirtide, quote unquote, failures are then switched to our regimen, and then after 24 weeks post-status switch, we are looking at differentiation in target not detected RNA. So, we believe that ECLIPSE 1 and ECLIPSE 2 combined, you know, are really the trials that will allow us to file for marketing application in the U.S. and in Europe. And then the ECLIPSE 3 trial is really there to support our pricing and reimbursement. So, that's a trial where we're really combining head-to-head bulevirtide with our regimen and looking at, again, 48 weeks target not detected. So, the combination of all three of them really gives us a very comprehensive package that we believe will set us up for success.
Yeah, sounds great. So, given the lack of options that patients unfortunately have right now, what paths are you exploring from a regulatory point of view in terms of accelerated approvals, regulatory designations, and the like?
Yes, I think it's very heartening to see that the discussions with the regulators are such that the unmet need is absolutely recognized, and so we already have Fast Track designation in the U.S. We were recently awarded Orphan Drug Designation by the EMA, and of course, you know, because of the unmet need, we're doing everything we possibly can to further accelerate, so we are, you know, looking into Breakthrough designation in the United States. We're looking at PRIME in Europe. I mean, the goal is really to take this regimen to patients as fast as we can.
Okay, so let's switch gears and talk a little bit about Hep B now. Excuse me, and then maybe to start, summarize the key data that you had for that program as well at AASLD and how you're thinking about the commercial opportunity there?
Yes, so the data we presented at AASLD, again, for hepatitis B, what we're trying to achieve is a functional cure. So, the data we presented was 48 weeks end-of-treatment data, so not yet functional cure data, but that data is sort of, you know, a precursor of what you might expect six months of treatment down the road. What we saw is that in a subset of hepatitis B patients with low starting S-antigen levels, below 1,000 IU per mL, that with our doublet, so tobevibart and elebsiran combined, we saw 39% S-antigen loss. And with our triplet, which is the doublet combined with interferon, we saw 46% S-antigen loss. So, these are really good data, sort of as a starting point to see what might come down the road.
What was also really interesting, I think, is that we saw a really good correlation between S-antigen loss and antibody generation against the HBV virus. And again, that's really what you need. You need immune control to achieve a functional cure down the road. So, we're now eagerly looking forward to the quarter two data next year. And once we have functional cure data, obviously, we will determine what the next path is going to be. Yeah, I think that's all we have.
Is that data in 2Q next year very, like, black or white? Is it a very binary outcome in terms of being a functional cure or not?
Yeah, I mean, what we have learned from talking to a lot of key opinion leaders is that, you know, they're looking somewhere for a functional cure rate between 20%-30%, depending on whether it's interferon sparing or not. So, you know, that's sort of what you would be looking to see. And as you know, we have only one competitor that is in phase III that, you know, has been putting out some functional cure data already. So, you know, that will be taken all together as we look into this.
If you're able to attain that when these results come out in the second quarter of next year, what would be the presumed next steps for the program?
Yeah, so one of the things that we certainly realize is that in contrast to hepatitis Delta, hepatitis B trials are obviously very large trials, you know, a totally different, you know, approach that is needed there, large phase III trials, very different again from Delta, which is designated as an orphan disease. So, we are going to explore whether we would be working with a partner on that program, but again, everything will be guided by the data.
Okay, so let's shift gears over to oncology and wanted to talk, obviously this T-cell engager, these assets you got from Sanofi, very exciting space, also seems like an evolution kind of in the strategy for Vir overall. So, can you sort of talk about the strategic rationale and why you guys decided to do this?
Yes, so again, I mean, Vir is really all about understanding how you can harness the power of the immune system to fight disease, and this, you know, again, these T-cell engagers, the concept fits perfectly into that paradigm. There were a number of things that we felt was very attractive, so first of all, we have really deep expertise in B-cell and T-cell biology, obviously, which is very important for this space. We also have deep expertise in protein engineering, antibody engineering, which again, for design of BiTEs and T-cell engagers is very relevant. When we looked at the programs, you know, again, the unmet need in each of these areas, and we are targeting HER2, PSMA, and EGFR, unmet need is still very, very high. If you think about five-year survival rate for HER2 metastatic breast cancer, it's 44%. For HER2 colorectal cancer metastatic, it's 13%.
Even though a lot of people think, oh, prostate, you know, there's so many things there as well, you know, five-year survival rate is only 34%. Then for EGFR, again, there, depending on the cancer type, you're looking at five-year survival rates of just 3%-38%. So, the unmet need is still very, very high. And I think that we have now learned that T-cell engagers are a really powerful modality. We already know that the biology works. We know that T-cell engagers work. There's 10 T-cell engagers already on the market, mostly for blood cancers. But the real, you know, the real issue that has been holding T-cell engagers back is toxicity, you know, CRS and other on-target off-tumor effects.
And so, we believe that with our technology, the Pro-XTEN technology, we can really mask those T-cell engagers, both on the tumor antigen binding side and on the T-cell binding side. So, it is a dual mask. And the hypothesis is that these masks are only cleaved off in the tumor microenvironment, and that is where they will exert its action. So, you know, carrying the potential for a much safer therapy, ability to dose higher, and hopefully see much better efficacy down the road.
Okay, so you mentioned this event in early January that you'll be hosting. What can investors expect there in terms of initial results that we might see?
Yes, so in January, we will be discussing, you know, initial data. Again, we're still in dose escalation for both the HER2 and the PSMA program. There's still, you know, a long way to go, but we will be able to share initial safety data and also initial signs of clinical activity on those programs, and again, you know, the idea is then for EGFR first in patients to start also in the first half of next year.
Okay, and I'm sure this is going to be informed by the safety data we'll start to see, but how do you think, at least at this point, about exploring combinations with your T-cell engagers or expanding into additional tumor types beyond the first couple that you're looking at?
Yes, I mean, obviously this will all be guided by data, but one of the promises of masked T-cell engagers, and I think, you know, that the field is still new, but I think there's certainly signs now that, you know, this could really work. The real promise is that you can come up with very safe medicines compared to a lot of other modalities in the field, and that, of course, lends itself to combinations. So, you know, that's certainly something we are thinking about. In our HER2 trial, there is already a combination cohort with Pembro.
Again, we won't be sharing data about that in January, but in prostate cancer, of course, again, if you can come up with a really safe masked T-cell engagers, there will be a possibility to combine with, you know, androgen receptor inhibitors or other, you know, immunomodulators down the road.
Okay, so final question here in our last minute, it's a bigger picture question. Curious how, you know, Vir is managing this, your capital deployment sort of priorities between now infectious disease and also oncology.
Yes, so we are fortunate to, you know, have $1.19 billion in cash at the end of third quarter, and we are really thinking about, you know, the most optimal way, of course, we spend our resources and our capital. Clearly, our Delta program is a top priority. We are going to enter registrational trials in the first half of next year. That's going to be a top priority of, you know, where we focus our capital. Hepatitis B, as I mentioned, sort of remains to be determined. We're going to look at functional cure data, and then for our T-cell engagers, again, we're going to be guided by data where we're going to put, you know, our money and drive the most patient impact and value for the company.
Terrific. Well, thank you very much for being here. Really appreciate it.
Pleasure. Thank you.