Good morning, everyone. Welcome to Barclays Global Healthcare Conference. My name is Gena Wang. I cover SNCC Biotech in the U.S. It is my great pleasure to introduce our first presenting company, Vir Bio. With us today we have Marianne De Backer, Chief Executive Officer. So, Marianne, before we dive into the specific questions, maybe do you want to give a brief overview of Vir and then we can, you know, discuss the specific topics?
Of course. Yes. So thank you, Gena. Thank you for hosting Vir Biotechnology here at the Barclays Conference. Really appreciate it. And welcome people here in the room and, of course, people listening in on the webcast. Yeah. So Vir is an immunology company. And what we are, our vision is really to power the immune system to transform patients' lives. And what that really means is that, you know, when people are suffering from an infection or there's cancer cells that start developing in their body, it's really often the immune system, the versatility of the immune system, that determines the outcome and whether patients get sick or not.
What we are doing is we have very unique technology platforms that allow us to bring tools to patients and to help the immune system really fight disease and to tip that balance in favor of patients. The two main platforms that we have, one is antibody platforms. So we have proven to be able to come up with very unique antibody therapeutics that we also engineer now using AI. And the second platform that we have is allowing us to generate in vivo, again, unique T-cell responses against infections or cancer. So those are our two technology platforms. What is most important, though, is of course the therapeutic candidates that we have in our clinical pipeline. And we have this year some really, really important catalysts coming up for the company.
Already in the second quarter we will be reading out more data on our phase 2 hepatitis delta trial. And then later in the year, in the fourth quarter, we will be reading out our, our full, phase 2, more than 60 participants. Also this year, already in the fourth quarter, we will be reading out our end-of-treatment, 48-week data on our phase 2 hepatitis B trial. Again, important data for the company. And then finally we have a phase 1 program, based on our, T-cell-based viral vector platform for HIV. And also in the second half of the year we will have, proof of principle data, and early immunogenicity data that will tell us whether the platform works. And if it does, can be a springboard to, to other applications. So again, this year will be very important to us.
Besides that, we have a number of preclinical programs that are within, you know, 9-24 months of going to IND.
Great. Thank you. So maybe, Marianne, you know, as a new leader of the company, so like, where do you see, you know, the full, you know, what is your vision for Vir? And you described, you know, what, what is Vir, Vir now. You know, what is your vision for Vir? And which are the important programs or candidates you, you think can excel to the next level?
Yes. So seven years ago when Vir was founded, it was really founded on the premise of the fact that there were a lot of, there was a lot of unmet need in infectious diseases. And it was really not getting the attention that it needed. And so the company has, you know, had an incredible path. And if you look at the drug discovery capability that we have within Vir, two of the drugs that were discovered within the Vir labs made it all the way to patients. So sotrovimab is the most known one for COVID, an antibody that went to millions of patients. And then Inmazeb, an antibody against Ebola, was the other one. So I think the company has proven that the technology platform is really, really powerful.
So as I came in as a CEO, I have prioritized the antibody platform because I think that's an area where we are truly world-class and where we can really differentiate. And beyond using the technologies of the past, as I mentioned, we now also have an AI platform that allows us to really select therapeutic candidates much faster and with very unique properties. So the focus on the antibody platform has really been very important for us as a company. And then we have such unique technology platforms that it would be a shame to only focus in the area of infectious disease. We are already working on all the major unmet needs in infectious disease. We talked about hepatitis. We talked about HIV. We have an RSV preclinical program. We have an influenza prophylaxis preclinical program and so forth.
But we really have the technology platform that allows us to open up the aperture and go beyond that. So what we are really focusing on is other viral-associated diseases. That could be viral-associated cancers. And again, other areas where targeting the immune system really makes a difference because that's where our really unique expertise lies.
So, Marianne, you also, you know, have like, Vir has an extremely strong cash balance. That was very unique for biotech companies. And then, you know, what, what is your vision to deploy this cash and then putting the use for the investment? And what will be the direction you will be thinking?
Yes. So, at the end of last year we had a cash and investments balance of $1.63 billion. We are, of course, as I mentioned, we have very important data readouts on our hepatitis delta program already coming up second quarter. And then hepatitis B already coming up this year fourth quarter. So the focus is really going to be depending on the data readouts to make sure that we can bring those programs to the next big value inflection points, and really accelerate, you know, creating value from those programs. Beyond that, you know, the great thing about having a healthy balance sheet is that you can also think about innovation, and bringing innovation in from the outside.
Our focus there is really to look at early clinical programs or CLO programs that are close to the clinic, again, to bolster our pipeline and to create value inflection points for, you know, the company and also, you know, really address unmet need for patients. That's really gonna be important.
Could you give some, you know, direction, like what kind of indication that could be?
Yes. I can, I can, share that again. Other viral-associated diseases is very obvious because we have deep knowledge in immunology. We have deep knowledge in virology. And we also have a world-class, small discovery team in oncology. So for example, viral-associated cancers would be an area that we would, would be looking into. But again, you know, we are looking at other areas where, again, the type of technology that we have or immune targeting really makes a difference and where our knowledge, our deep knowledge in these fields, can be an asset. And also I wanted to, to add, Gena, that at the end of, of this year, actually in the fourth quarter, we're going to do an R&D Day. It's gonna be an opportunity for us to show, you know, everything that is going on in the company.
I think the quality of our science is really impressive. I think it will also give you then a good idea of what our other areas where we can really drive value.
Okay. Great. Thank you. So now we can dive into your important data, upcoming data, HDV program. So maybe can you lay out the data set that will be shared, you know, for the phase 2 update in the second quarter?
Yes. So maybe for people not as familiar with hepatitis delta, so it's the most severe form of viral hepatitis. And people who are infected with hepatitis delta virus, it's a virus that can only infect patients that are already infected with hepatitis B virus. And so what happens is if you're co-infected, you progress to cirrhosis, you progress to liver cancer, and you progress to death much faster than if you're infected with hepatitis B alone. So it's a very serious disease. There's an estimation of about 12 million people in the world living with hepatitis delta. But it's a hugely underdiagnosed disease. So there's also an estimation that there might be 60 million more people actually in the world infected with delta that just are not aware of it. If you look at the United States, we estimate that there's about 100,000 patients here.
In Europe the estimation is about 200,000. There's a high unmet need. However, there's not a lot of options out there for patients. In the United States there's really nothing, on the market. There's nothing available for patients. In Europe there is one option available which is a daily, subcu. We have a regimen, a treatment regimen that is a combination of an siRNA and an antibody that we discovered within the Vir labs that, in six participants last year at AASLD, we showed initial data. We treated six patients, with a combination of our siRNA and our antibody elebsiran and tobevibart. Only after three doses, so only after 12 weeks, we already saw very promising data in the sense that all six patients had their HDV RNA, which is a measure of infection, drop below the lower limit of quantification.
So that was a promising sign. And so what we did is we have enrolled an additional 63 participants. And we just announced that we have actually enrolled those participants much faster than we had anticipated, so 4 weeks ahead of schedule. And that will allow us to read out data in the second quarter and also at the end of the year. In the second quarter we will have 15 participants at 12 weeks of treatment of the doublet regimen, so the elebsiran and tobevibart. And also 15 participants that have been treated with tobevibart, the antibody alone. We will also already have 10 participants that have been treated for 24 weeks, again, both with the doublet and with the monotherapy.
So that set of data I think will be very informative and will give us a good idea if the data that we have seen in the six participants that we reported on last year in November, AASLD, and earlier this year, if that is reproducible in a larger set of patients. And then again, the full set of 63 participants, we expect 24-week data in the fourth quarter.
Okay. That's super helpful. So, maybe, you know, one question is the initial six patients, and all of them, you know, were non-cirrhotic. So what makes you decided to include cirrhotic patients in the future enrollment?
Yes. So in the patients that we have enrolled now for the phase 2 trial, about 50%, 50% of the participants are CPT-A cirrhotic patients. And, you know, as is the case for any therapeutic that one wants to develop, the idea is of course to bring it to as many patients as you probably possibly can that are in need of a therapy. And remember what we're trying to do here is really develop a lifelong therapy. So this is a treatment that is only once a month, is lifelong. And it is really important to also look at cirrhotic patients because, of course, as I mentioned before, patients that have delta progress to cirrhosis faster than patients that have hepatitis B virus infection alone.
So it's really important to see, you know, can we achieve the same efficacy, safety in patients that are cirrhotic. What we have done before is a small hepatic impairment study. It was also presented at AASLD last year where we looked at cirrhotic patients and we looked at how the drug exposure is of elebsiran alone or tobevibart alone. And, in that hepatic impairment study we did not see any meaningful difference in safety or PK.
Okay. So then from the clinical benefit perspective, if they were able to reduce RNA level at a similar level, do you see any reason that clinical benefit could be different between cirrhotic patient versus non-cirrhotic patient?
Well, you know, based on what we have seen just from drug exposure in cirrhotic patients, you might not expect any difference. However, we really have to wait for the data. And again, because we have been able to enroll 50% of the patients that are CPT-A cirrhotic, you know, our data in the second quarter will already give us a good view on that topic.
Okay. Good. And then, when we look at the initial 6 patient data, we do see like baseline HDV RNA level lead to slightly different benefit. And then the lower baseline seems like was able to achieve better reduction. So are you planning to enrich patient in that patient population or are you still thinking more of the broad range?
Yes. Again, our ambition is really to come up, of course, with a regimen that can cover an as broad as possible population of patients that really need the regimen. And again, the unmet need is high. There's nothing available to patients here in the United States and a lot of places. And, you know, we think it's premature to start segmenting at this moment in time.
But again, the data that we will get in the second quarter and of course the data that we will develop over the year will give us a better insight for, of course, our potential registration of trials.
Mm-hmm. Very helpful. And, when we look at, you know, the, say, 2Q data and then also 4Q data later, do you have a minimum threshold in mind regarding, say, for the approval pass in terms of a percentage of patient that reach below lower limit of quantification of HDV unit?
Mm-hmm. Yes. So actually the regulatory bar is not very high. You know, the current guidelines say that if you have a two-log decline in delta RNA or you go below the level of detection combined with ALT normalization, you know, that is actually good enough for the regulators. So again, the data that we have seen in the 6 participants is really promising, because again, it's only after 12 weeks of combination treatment. And we had actually 5 out of 6 participants drop below the limit of detection. And as I mentioned, all of them drop below the lower limit of quantification. So, you know, we will look at our data. We will have, if the data looks promising, we will have conversations in the third quarter with regulators.
Of course we will have that conversation around, you know, trial design, expectation around, the size of the trial, the primary endpoint. So, you know, we should be in a really good position, if the data pans out to be positive to know much more by the third quarter of this year.
So, I know you still have to talk to the regulators, but, you know, any initial thoughts on the approval path, registration path for the HDV?
Yes. I think it's a little bit premature. What we do know, of course, is that there's a certain size of the trial that you need to get, not so much determined by the efficacy side but more by the safety side.
So, we will have to have that conversation with the regulators as to how large the trial will need to be, for safety reasons. We have actually used, as you know, Gena, the same combination of therapeutic candidates in our HBV trial. And so this is a regimen that has already been in quite a number of HBV patients. So the question will be, will the regulators want to see a certain, you know, number of patients that are Delta or will they take into account already the safety data that we have in B? So again, a lot will determine on the data we have. The unmet need is clearly high but of course the regulators will need to give us some guidance there.
Okay. Very helpful. So maybe now move forward to your HBV program. We've seen quite some cohort data in the past. And it seems that longer treatment is necessary to achieve, you know, competitive cure rate. So, for your next update, you know, what is the bar for cure rate, regarding I think the next update will be cohort 4, 6, and 8?
Correct. Yeah. Yeah. Yes. So again, maybe to set the scene, hepatitis B, or chronic hepatitis B, there's probably about 300 million people in the world living with chronic hepatitis B. And over 50% of the liver cancers are thought to be caused by that virus. So again, it's an area of high unmet need. There isn't a functional cure available at this moment in time despite a lot of attempts to find one. There's about an estimation of 2 million people with hepatitis B in the United States and about 3 million in the EU5. So it's a sizable population. But again, the sort of goal is for us and for others to try and find a functional cure.
Meaning treating patients for a finite amount of time and then taking them off treatment and they will have their viral disease in control. So, to your question as to what it is you need to see, so what we have done up to now is we started actually with combining our siRNA with interferon alpha. And we looked at, you know, after 24 weeks, what is the level of HBsAg loss which is a measure of activity that you see. And we got about 26% of HBsAg loss which was, you know, a really good result. Six months after taking people off treatment, we ended up with a functional cure rate of 16%. That might not seem a lot but it's one of the best results out there.
This was a trial in all-comers, all-comer HBV patients and 16% of the patients were functionally cured. So what we then did is we added our antibody tobevibart to that regimen, actually to the siRNA elebsiran with and without interferon. And we're trying to determine, is there additive effect here? And can we reach higher levels of functional cure by using this combination? So the data that we have shown in AASLD last year were 24-week data. And you're absolutely correct, Gena, what we have seen is that certainly we need a longer duration of treatment. So what we saw though at 24 weeks is that the HBsAg loss, if you combine elebsiran, the siRNA, and interferon alone versus adding tobevibart to it, that we got a threefold increase in HBsAg loss. So at least directionally this was going in the right direction.
So now the data that we will have at the end of this year, 48 weeks end of treatment, the question is what does that need to look like? And what does functional cure need to look like for physicians and patients to be really interested? So we had originally set ourselves the goal of achieving a 30%-30% functional cure rate. However, we were at AASLD in November meeting with 11 of the top KOL hepatologists in the world and we were asking them that question. I mean, what is it that you need to see to really, you know, take a regimen and, and treat your patients, start treating your patients? And the feedback that we received is that they would be looking at, you know, 25% functional cure rate approximately for a regimen that contains interferon.
Again, interferon has some side effects, but, you know, that was the guidance that we were given. And if the regimen does not contain interferon, then actually that functional cure rate could actually be a little bit lower. Again, I think we are here at the start of hopefully a journey where functional cure rates will continue to increase, but the bar now is relatively low because there's again, there's really nothing out there that can cure patients.
Okay. That's very good. So maybe we still have a little bit, two minutes left. Maybe I wanted to ask you, out of all the pipeline you did say HIV data update, so maybe like, you know, what, what would be the data sets we should be focusing on?
Yes. So for our HIV phase 1 program, VIR-1388.
Yeah.
Yes. So again, this is a viral-based T cell platform. And what we do is we bring a viral vector, CMV, into patients or into participants. And that vector carries an HIV insert. The idea is that, by using this unique vector, CMV, that we will be generating a set of CD8 T cell responses that can have long-term protection of patients for infection against HIV.
What we will be looking at to see in the second half of this year is really do we create those CD8 T cell responses? Do we create effector memory CD8 T cells? You know, if that is the case, that would be really promising.
but we will be doing a full analysis of, you know, CD8 T cell, CD4 T cell, cytokines, chemokines so that we really understand what the factor is inducing in the human body and how protective this could be against infection for HIV.
Okay. Yeah. Last question maybe. How's the CMO search going?
Oh, yeah. Yeah. The search is well underway.
Actually in between all the meetings here we're also having some interviews. So, yeah, you know, we have a number of candidates also once we announced that our CMO is leaving that have reached out. So I think we have a really strong subset of candidates. And what we're really looking at is people that have late-stage development expertise, have really brought, you know, important drugs through clinical development and to patients and have that deep clinical development and regulatory expertise. So, yeah, but we have some good candidates and hopefully we can progress the search in an expedited way.
Thank you very much, Marianne.
Yeah. My pleasure. Thank you, Gena.
Thank you, everyone.