Thanks for joining this session with Vir. My name is Alec Stranahan, and I'm Vice President and Senior Biotech Analyst covering Vir here at B of A. And I'm pleased to be joined by Marianne De Backer, Chief Executive Officer of Vir. Marianne, thanks for being here.
My pleasure.
Great. So I believe Marianne is gonna run through some high-level prepared remarks to start, and then we'll jump into the Q&A. So with that, Marianne, over to you.
Okay. Thank you, Alec. A real pleasure to be here. So, you know, Vir Biotechnology is a company with a vision to power the immune system to transform lives of patients. And what that really means is that we want to equip the immune system of patients with new tools to either, you know, fight infection or fight cancer. And at Vir, we have two very important platforms to do that. The first one is our antibody platform, which allows us to come up with very unique therapeutic antibody candidates that nowadays, of course, are really protein -engineered using AI. And that platform has already been really productive. There's two antibodies that are already on the market, one for Ebola and one for COVID.
Of course, our next antibody that is gonna be really important is in development for hepatitis delta and hepatitis B, and we'll be talking more about that tobevibart. Our other platform is based on a CMV vector. We call it our viral -based viral vector platform, and that is a platform that allows us to induce very unique T- cell responses that are very potent, broad, and also durable. So we have a program in phase I development for HIV prophylaxis that is using that platform. Two very powerful platforms. Certainly, the antibody platform that is proven, and for the CMV platform, we will have proof of immunology data coming up in the H2 of this year.
Now, this year is really, you know, very much focused around our hepatitis delta and our hepatitis B programs, where we have critical data readouts coming up. And beyond that, you know, we have a rich preclinical pipeline. We have four programs that could enter the clinic in the next 12-24 months, and all of that is really underpinned, as you know, with a very strong balance sheet. We have $1.51 billion in cash. And we have been doing a lot of effort in, you know, bringing down our operational expenses, really focusing our efforts on the programs that can drive the most value, both for patients and for shareholders. So yeah, it's a really exciting time for Vir, and I'm also excited to talk with you more about our plans.
Perfect. Great. Now we'll jump into the Q&A. I've got a few here, but I encourage those in the audience, if you have questions, just raise your hand. Someone will bring a mic around, and you can, you can ask your question. Marianne, maybe, maybe just to start on hepatitis delta, since this is, maybe, the next data update, we should be getting it in Q2. Maybe just to start, I think it'd be helpful to first review the latest data we saw from SOLSTICE, earlier this year at AASLD. Early days, six patients, but pretty encouraging early results.
Yes, absolutely. So maybe just to set the stage, hepatitis delta is, you know, the most severe form of viral hepatitis. And, hepatitis delta is just a tiny RNA virus that requires hepatitis B for its replication. So, a patient that has a delta infection already has a hepatitis B infection, and it's the most severe form of viral hepatitis because if you have that dual infection, you progress four times faster to liver cancer and two times faster to death. So it's, it's, you know, really, a very severe disease. The estimation is that there's about 12 million people in the world living with hepatitis delta. And if you look, for example, in the United States, if you were diagnosed tomorrow with hepatitis delta, and I hope not, there would really be no treatment option for you available.
So it's a high unmet need, and there's really nothing available for patients in the U.S. There is a standard of care in Europe that is certainly, you know, falling short in a couple of ways because, you know, people have to give themselves a daily sub-Q injection for the rest of their lives. And for those patients that actually can do this, you know, can adhere to such a regimen, they have less than 50% chance that they actually achieve a clinical benefit, and only one in 10 chance that they get to really undetectable delta virus RNA. And again, you know, delta virus infection, it's a chronic viral infection, and in any chronic viral infection, also like in HIV, like in HPV, what you really want to achieve is undetectable viral DNA.
So what we have set out to do is we use a combination of two products. As I mentioned, we have an investigational neutralizing antibody called tobevibart, and we have an siRNA targeting S-antigen called elebsiran. So tobevibart used to be called 34-34, and elebsiran was called 22-18, just as reference. And what we have shown last year at AASLD in first 6 participants is that if you did a 12-week lead-in of treating patients with either elebsiran alone or tobevibart alone, and then after 12 weeks, you switched those patients that hadn't achieved, you know, the endpoint desired to a combination therapy, we saw that already after 12 weeks, and that is just three doses, because our dosing is once a month-
That already after 12 weeks, we saw a very sharp decline in delta RNA, and five out of six patients achieved undetected HDV RNA levels below lower limit of quantification, and six out of six below lower limit of detection. So those were very impressive results. Again, only in six patients, as you mentioned. So what we are now looking to do and we will have a late breaker at EASL in June, on June fifth, to be precise, we will be looking at a larger subset of patients.
Mm-hmm.
We will be studying both the combination of tobevibart and elebsiran every month, dosing, and also, tobevibart as an antibody alone every two weeks dosing. We will have about 30 participants that have been on treatment for 12 weeks with each of that regimen, and then probably about 20 that will have been on 24 weeks of treatment, again, with each regimen. So the data that we will be presenting at EASL will be very informative in understanding, can we really replicate, you know, the results that we saw at AASLD with six participants? And if that would be the case, then, you know, this could be really transformational for patients.
Right. And I guess, what is the ultimate goal of therapy in these patients? And is there any difference between cirrhotic versus non-cirrhotic patients in terms of how, like, the goals of treatment?
Yeah. So our goal is a chronic therapy that, of course, is very efficacious and safe, and also much more convenient for, for patients. So in our first study of the 6 participants, we actually did not include any cirrhotic patients. However, in the 60 participants that we have enrolled in the SOLSTICE trial, that is gonna read out again, partially in, at EASL, already 50% of the patients are CPT-A cirrhotics. So we will be able, you know, to look at is there a difference in, you know, efficacy, safety in that subset of patients. It is probably important to note, though, that we did a hepatic impairment study. So we looked at if you give either elebsiran or tobevibart to patients that are cirrhotic, is there a difference observed in safety or PK? And we haven't seen any meaningful difference.
So based upon that, you wouldn't expect a big difference, but again, the data will have to show us.
Okay. And, you know, we'll get the Q2 update. What is your thought around path to registration once you have this data in hand? Will you wanna wait for the Q4 data to approach the regulators, in terms of, you know, follow-up study or path to registration, or do you think the Q2 data could inform those conversations?
Yeah. So as mentioned, we will have data around, you know, 30 additional participants for each of the, of the fifteen at 12 weeks for each of the regimen and 10 at 24 weeks for each of the regimen. And our, you know, hope is that depending again on the strength of the data, we can engage with regulators already in the Q3 . There wouldn't be any reason to wait until the end of the year. At the end of the year, of course, we will have, for all our 60 participants, 24 week data, and that will be the most complete and, and, you know, informative data set. But again, depending on how the data look like at EASL, you know, this will really guide us in what kind of path to take with regulators.
Okay. And you mentioned that there is no, you know, no drug approved in the U.S. There is one approved in the E.U. I know there's a bit of history there. Any learnings that you could take or precedents that you'd point us to in terms of understanding how the FDA may view an accelerated approval path in HDV?
Yeah, so for hepatitis Delta in the U.S., there's really no precedent, right? There's nothing on the market, so we don't really have something that, you know, we can point to necessarily. What we know is that for Europe, and again, that was sort of a first entry, of course, there was a conditional approval based on 24-week data, and then a more affirmative, you know, approval after 48-week data. But again, you know, we are planning to do a trial that uses bulevirtide as a comparator in the study, and it's gonna be a global study. And what that design is going to look like will really be guided by our conversations with both the FDA and the EMA, of course. Yeah.
Okay. Maybe now we can turn to Hep B. And I actually filled a script at CVS a few weeks ago, and they were heavily pushing their Hep B vaccination campaign, so it's definitely a topical issue. But I guess, Marianne, at a high level, you know, what gives you confidence that you can achieve a functional cure in HBV? 'Cause I think that's your stated goal for these patients.
Yes, and maybe again, to set the stage, there was a report that was released in March from the WHO that sort of reconfirmed that there's more than 250 million people in the world living with hepatitis B. About 1.6 million estimated in the United States, 2.8 million in Europe. So, you know, again, patients that are infected with hepatitis B, it's a bit of a silent killer, but eventually, of course, it leads in a large portion of those patients to cirrhosis, liver cancer, you know, patients need to get liver transplants and so on.
Of course, there is therapy that is available right now, but there is nothing that really leads to a very high level of functional cure. And what we want to really achieve is a functional cure rate of about 30%. That is sort of our stated goal, and that 30% is really meaningful, because again, the only thing that is available to patients right now for achieving a functional cure is a treatment for 48 weeks with interferon alpha. And after doing that for 48 weeks, the functional cure rates that are achieved are somewhere between, you know, 3%-7%, so really not very impressive. Now, why do we believe that we really have a shot on goal here with our assets?
So first of all, we have started by the hypothesis that in order to really make a meaningful impact in hepatitis B, you need to have an approach that involves both antivirals and immunomodulators. And we have called it our stop and clear approach. So we use really our siRNA to stop the virus from, you know, producing more S-antigen and, you know, really disrupting the transcripts of the virus. And then we have our investigational antibody that is both an entry inhibitor and also leading to, you know, immune clearance of the virions. So by combining, you know, again, the direct antiviral and an immunomodulator, we think we really have a shot at this.
And the first data that give us, you know, some, some hope that this could actually really be true, is when we started combining our, our siRNA elebsiran in initial stage with interferon alpha. So when we did that, and we treated patients for 48 weeks, we achieved S- antigen loss of about 26%. And you have to, again, remember, as I mentioned, if you treat patients 48 weeks with just interferon alpha, you get, you know, to a functional cure rate of 3%-7%, and you get almost the same at 48 weeks end of treatment. And if you treat patients just with an siRNA alone for 48 weeks, you really achieve, you know, not close to nothing.
So the combination of the siRNA and the interferon clearly is doing something more, given that we achieved 26% end of treatment S-antigen loss, and then after six months, so functional cure rates was about 60%. And this was in all comers. We did not, you know, stratify patients. We really took patients of all, you know, all S-antigen levels to start with, and that 60% is really one of the best, you know, data that is out there. So that was a really good first insight into the fact that indeed, combining an antiviral with an immunomodulator, in this case, interferon alpha, could lead to much better outcomes.
What we then did in our MARCH Part B trial is looking at, you know, what if we add up our antibody tobevibart to that combination, either to elebsiran alone or to elebsiran plus interferon. So we only have the data that we presented earlier at 24 weeks, but what we saw at 24 weeks is that we already had a three times higher S- antigen loss than just looking at siRNA with interferon alone. So again, clearly the antibody is doing something in addition. So what we are now looking out for is really our 48-week end -of- treatment data, and that's data that we will have available in the Q4 of this year.
And then again, you know, I think that will already be very informative because, again, our end goal is, you know, to get to, you know, around 30% functional cure. And then mid-next year, you know, after a finite amount of treatment, and then taking patients off the treatment for six months, we will have our, our functional cure, read out. So again, both at the end of the year and then next year will be very important data readouts for our hepatitis B program.
Okay, and that kind of partially answers my next question, but I think it's worth drilling down a little bit further. You know, how should we be thinking about the MARCH 24-week data that we've seen in the context of the upcoming 48-week data readout? Is there a deepening of response that you would expect over time, or, you know, any read-through, you know, from that 24-week data that we could extrapolate on?
Yes. So when we looked at 24-week data of elebsiran, so the siRNA with interferon alpha, we achieved only 5% S- antigen loss. However, if we looked at 48 weeks, we had a five times higher S-antigen loss. So it went from around 5% to, you know, 26%. So clearly, something is happening between 24 and 48 weeks. The question now is, what will that look like for the combination of elebsiran with our antibody tobevibart, and the same combination with interferon added? What we do know is that, again, interferon tends to achieve an effect later in the regimen, so you could, you know, imagine that also in the case of our combination, our triple combination, you would see a later effect. But again, that's sort of, you know, guesswork at this time, and we will need to look at the data.
Again, I think will be very informative is where do we land, at the 48-week end of treatment, data as to S-antigen loss? So it is known that if you treat with interferon at 48 weeks, if you have a certain outcome, again, 3%-7%, you really don't have a drop-off. Once you take patients off, you still have a functional cure rate that is approximately the same. However, that's not what we saw in our combination of interferon with elebsiran. So we saw a drop-off from 26%-16%. So the question is now, when we are going to look at our 48-week data, will we see a drop-off or not? In any case, again, we have really consulted a lot with KOLs.
And what they are saying is, again, the unmet need for a functional cure in hepatitis B is really high, and they're actually, you know, put the bar for a functional cure rate at around 25% for an interferon-containing regimen. And it could actually be a little bit different, and even, you know, lower for one that is without interferon. So again, you know, the data that we will have at the end of the year will be very informative.
Okay. Yep, definitely looking forward to that. And I wanted to touch on your HIV program. I know Hep Delta and Hep B are the majority of the focus for many investors, but I think HIV will begin to grow in importance from the pipeline, especially with the H2 data readout for VIR-1388. I think you said that this will mostly be immunogenicity data. Maybe you could just talk about your approach within HIV, and how validating could this immunogenicity data actually be for the asset?
Sure. So, as I mentioned at the beginning, we have two fundamental platforms. One is our antibody platform, and of course, you know, we are building now to tobevibart and a number of other assets, to further develop in the clinic. For our CMV platform, which is our second platform, our first application is really in HIV prophylaxis. And so VIR-1388 is currently in clinical development, and the data that we will have in the H2 of this year is the first really potential proof of concept data that we can achieve a virological immunological response that is very specific to HIV.
Because what we have done is, again, the Holy Grail in HIV prophylaxis is that you would be able, with ideally, you know, one or only a couple of, you know, treatments in a lifetime, be able to generate a very strong, broad, and durable protection against HIV infection in your lifetime. Now, again, that's the Holy Grail. It's not easy to achieve. HIV vaccination has not proven to be successful. So what we are trying to do is we use a CMV vector because it has all those attributes. When CMV, you know, infects a person, you get those very, you know, again, very potent and broad and durable responses.
We have used CMV really as a vector, and we have inserted HIV portions of the genome. We call that immune programming, so that the T -cell response that potentially will be generated in a patient or in a person will be specific to HIV. And now, again, H2 of this year, we will see the initial data looking at CD8 T- cell responses, CD4 T -cell responses, specificity of T- cell response. So that will be very informative for the HIV program. But also, you know, if that proves to work, then it is very important also for our platform-
Mm-hmm.
Because we have a next- generation CMV-based asset, preclinical, that is targeting human papillomavirus, so for really HPV cancers. And again, the mechanism is very similar. It's, you know, using the CMV vector, introducing HPV-specific genes, and then seeing if we can generate those very specific T- cell responses against the human papillomavirus. So again, for the platform, this will be a very important data readout.
Right. Right. You know, you mentioned we talked through those three programs, but you know, there's a lot of other applications you could pursue beyond infectious disease, to say, immunology or other areas.
Viral-associated cancers is a very obvious one.
Yeah. Yeah. I guess, maybe just talking about the cash position, you know, greater, you know, around $1.5 billion on the balance sheet, feels like plenty of dry powder to sort of power your pipeline ambitions. Where are you most focused today in terms of capital allocation? Where do you see sort of the, the expansion of the pipeline coming from?
Sure. So, you know, with $1.5 billion in cash, we are really well positioned to fund our hepatitis delta and our hepatitis B programs through the next really important value inflection points, and that's absolutely our priority. However, this balance sheet also really allows us to look at some external innovation. And so our focus there is really looking at early clinical assets in areas where we have really deep expertise. So we are really looking at opportunities where, again, our knowledge in immunology can really add something special to it and increase the chances of success. So, you know, those are the kind of opportunities we are looking into.
You know, we will be holding an R&D day in November where, you know, we will be happy to share more insights into, you know, the type of things that we are thinking about more on the research side and both on the business development side.
Okay. Okay, very good. And I know you're currently looking to fill a couple of executive positions in the company. You know, I guess, where are you in the search? When could we expect new executive appointments to be announced?
Yes, so we are currently conducting searches for our Chief Medical Officer and also for our Chief Financial Officer. So, both searches are in full swing. You know, we have very specific profiles of, you know, candidates that we are looking for in each of these categories, and we're making really good progress. But of course, I cannot give you sort of a date. But, again, it's of course a priority for us to fill those positions with, you know, top-notch candidates that can also really help us in, you know, taking the company to the next level. Because our ambition as Vir Biotechnology is really to become a fully integrated commercial company, and, you know, potentially with really good data on hepatitis delta, that could be our first foray in becoming a commercial company.
So again, we are really looking at profiles of candidates that can help us drive success in that journey.
Right. Yeah, it's definitely a-- It could be an opportunity, actually, to, to strengthen the leadership, you know-
Correct
-as we sort of look forward to the next leg of growth. You know, maybe along those lines, when you think about what a 2026 or 2027 year could look like, you know, which is obviously what you're building towards today, you know, how, how would you like the company to look, or, or what could be realistic in terms of pipeline stage at that time? Or, you know, any other aspects you'd flag that you're building to, to strengthen for the long run?
Yes. So as mentioned, our vision is really to become a fully integrated biopharmaceutical company, you know, with, of course, eventually, hopefully, hepatitis delta and B regimens on the market, you know, a number of late-stage assets, and then really, a very, you know, powerful early pipeline that builds on our platforms, right? What you can expect more in the, in the, you know, near to midterm is that our pipeline will be a mix of, you know, both infectious diseases assets, but also some assets in other therapeutic areas. Oncology is one of them. So it's gonna be a more diverse pipeline than what Vir has typically been in the, in the past.
I guess to that point, you know, what sort of will drive the shape of the pipeline in the future? You mentioned leveraging your core competencies, but in terms of the makeup of, you know, indications, whether it's infectious disease, vis-à-vis, you know, infectious oncology or immunology and technologies within that, you know, what does sort of the mix look like?
Yeah. So again, our focus is really to look at externally clinical stage assets that can strengthen the pipeline further and, you know, where we have a differentiated insight. So we are not going to go into something that, you know, we really do not know anything about. We are going to look for things where, again, our deep knowledge in immunology. We also have a very strong oncology research team, of course, deep knowledge in virology, but where all that knowledge really, you know, gives us a leg up in maybe an accelerated path for assets to bring forward.
Okay.
Mm.
That makes sense. And I know you've mentioned in passing some AI machine learning that you're building out internally. How are you balancing this, or how does this feed into, you know, the balance of external innovation versus driving internal development?
Yeah. So, you know, 90% of the antibody therapeutic candidates that we're currently working on have been identified through using our AI-based protein engineering platform now. So it's not something that stands on its own. It's really integrated in our drug discovery process for antibody therapeutics, and it's, I must say, really impressive. First of all, it allows us to come up with candidates much faster than before. And secondly, it allows us to come up with candidates that have very differentiating profiles that, you know, even though we have, I think, some of the best protein engineers in the world, we might not necessarily have come up with exactly those designs. So I think from both, you know, the ability to move faster and the ability to come up with truly more unique antibodies, I think this is a very exciting platform.
And of course, for now, we have been deploying that solely to our own pipeline. But, you know, we will be thinking through whether, you know, it makes sense to, you know, deploy that more broadly.
Okay, great. And we've got about a minute left, so I wanted to, you know, just leave it with any, you know, final thoughts that you'd want to highlight or, or wrap up.
I would say, you know, we have some very important data coming up in June from our SOLSTICE hepatitis delta trial. It's an area of, you know, very high unmet medical need. Again, there's nothing available for patients in the United States. And then we didn't talk about it that much, but, you know, we yes, we have a very healthy balance sheet, but we also have been doing a lot of work in, you know, reducing our operating expenses, focusing our pipeline, and really be more prudent in how we deploy capital. So I feel that, you know, we're in a really good position, and, and again, this year will be very important to us, with many catalysts coming up that that can potentially transform the company.
Right. Right. Definitely looking forward to the updates later this year, but I think unfortunately, with that, we'll have to end there. So, Marianne, really enjoyed the conversation. Thank you so much for participating.
Sure. Thank you, Alec.
Thank you.