So to summarize, the mechanism is still not clear but there aren’t early signals that it is due to the changes in HDV RNA and there are early signals that 3434 or tobevibart can solve for that.
Eva Privitera: And another question on the HBV MARCH trial. You’ve previously shown that high antibody titers were predictive of sustained surface antigen loss. Do you expect to present antibody titer data at the 48 weeks end of treatment data in Q4?
Phil Pang: So we have not yet guided to whether or not we will be sharing anti-HBS data along with the actual surface antigen loss, but we will be doing everything we can to provide as much clarity on our results at that time. So stay tuned.
Operator: Your next question comes from the line of Patrick Trucchio with H.C. Wainwright.
Patrick Trucchio: I have a a couple of follow-up questions on SOLSTICE program. So just first a clarification around the next data readouts. I’m wondering first, should we expect the next update or when should we expect the next update on the patient cohort data reported at AASLD 2023, specifically the proportion who achieve ALT normalization, which I understand can take longer than achieving the RNA below lower limit of quantification, as well as assessment of the durability of the virologic response? I’m wondering if that update maybe part of this data that’s coming in the second quarter or if maybe we would see the next cut there later this year in the fourth quarter? And then secondly, I’m wondering how we should think about the 44% of patients having compensated cirrhosis.
Is this a proportion of patients with compensated cirrhosis consistent with what would be expected in real world setting for patients with chronic HDV, or how did you decide on that proportion? And then how should we think about these key endpoints, like HDV RNA and normalization of ALT and as well the safety profile of the combination regimen in these patients with or without compensated cirrhosis?
Phil Pang: Well, Patrick, you’re going to challenge my memory to make sure I remember all those questions. But let me start with a compensated cirrhotic question, move on to the endpoint question and then finish with the durability question. So with regard to the compensated cirrhosis, the epidemiology on hepatitis delta patients and how many of them have compensated cirrhosis is not entirely clear, but it is certainly a large proportion, probably somewhere between 30% to 50%, that was not the reason why we ended up at 44%. As you can imagine when you’re enrolling this trial, we actually targeted around 50%, but you want to move also the trial enrollment as fast as possible. So right now, as I said, in my prepared remarks, is about 90% of the trial has been enrolled, that’s why it’s at 44%.
I expect that number to go up, because the only patients left in screening are all cirrhotic — are all patients with cirrhosis. So we’ll probably get 44% or maybe even 48% or somewhere around there. But what we really wanted to do was to get at least 10 to 15 patients with cirrhosis per cohort to be able to understand what the kinetics of viral decline is and ensure that there’s no obvious safety signals. So that’s how the 44% is just sort of the result of where we are in enrollment. With regard to the endpoints, I think it is important to remember that how we think about the endpoints is both historical as well as forward looking. So there are a few possibilities for the primary endpoint that I want to share with you. The first, of course, is the endpoint that was used by bulevirtide, which was a combined virologic and biochemical endpoint.
Specifically that virologic endpoint allowed either a two log decline or getting to the limit of detection virologically and then also requiring ALT normalization. But I think when you speak to physicians, providers and virologists, what they’ll say is they’re not sure what a two log decline actually means. For example, if you go from seven logs to five logs, you still have a hundred thousand copies of the virus in your blood per milliliter and that obviously does not sound good. So we think as well as clinicians that getting to undetectable or below the limit of quantification would be strongly preferred. So then you can imagine a forward looking endpoint, and I think this is a likely possibility, of requiring patients to get to the low limited detection or the lower limit of quantification and ALT normalization without allowing patients to achieve just a two log decline in viral load.
That would set a gold standard that I think we could definitely show a meaningful benefit on, because it would require everyone to, at the first instance, get to the lower limit of quantification where we would have a possible advantage over the standard of care. So I think those are some of the color I can provide for you around the primary endpoint. And then as far as your third question around durability, I would say that, we have actually not guided to the follow-up on those six patients. But as we’re going to have nearly 20 participants at 24 weeks, we’ll be able to share their kinetics of both viral load decline and ALT changes, which I think will be informative and we will look into sharing the six patient follow-up data as well in a future guidance call.
Operator: Your next question comes from the line of Eric Joseph with JP Morgan.
Eric Joseph: [Technical Difficulty] what you expect to be the ultimate treatment duration or kind of paradigm here with the [tobe-ele] combination, do you expect it to be finite therapy or chronic treatment? And if it is the former finite interval, I guess, how much sort of off treatment observation do you think you would — would you sort of hope to have going into discussions with regulators?
Marianne De Backer: Eric, the beginning of your question was a little bit difficult to understand.
Eric Joseph: Is the — in hepatitis delta, is the expected treatment algorithm going to be finite therapy or chronic therapy? If it’s finite therapy, how much chronic treatment follow up do you think you would have going into initial discussions with regulators?
Marianne De Backer: So what we are aiming to achieve here is the chronic treatment regimen for hepatitis delta patients. You want to comment further, Phil?
Phil Pang: So with that — in that framework of chronic viral suppressive therapy, as we currently know, it for example, for other viruses like HIV and for hepatitis B, there is no need for a follow-up therapy as there is not a finite duration therapy. I think one of the questions that can come up is, are we going to be following these patients for 24 or 48 weeks. And of course we’ll follow for both. But the question will be with regulators, is there any precedent for earlier data? And there is with bulevirtide, and that’s another discussion we’ll be having with regulators.
Eric Joseph: Anything you can share [Technical Difficulty] the tolerability profile in — among patients receiving the upfront combo regimen in the Q3 cohort?
Phil Pang: So I think that certainly we’re looking forward to the Q2 data from our SOLSTICE trial and the patients who have started what we call de novo or immediately on combination therapy without a lead-in. And what we’ve said is that we’ll have about 30 participants between the two arms, actually between mono and combo at week 12 and 20 participants at week 24. So you divide that into 15 of the patients will be through week 12 and 10 participants through week 24 in the combination arm and we’re looking forward to being able to share that data in Q2.
Operator: Your next question comes from the line of Alec Stranahan with Bank of America.
Alec Stranahan: Just a couple from us, you’ve mentioned in the past about expanding beyond infectious disease into say, immunology, et cetera. Are there any areas of immunology or targets to say even 20 that you see as particularly interesting? And would you say within your core competencies regarding antibodies and siRNA or would you be more maybe technology agnostic? And one question on how you plan to allocate your $1.6 billion roughly in cash. Maybe if you could break down percent spend on pipeline development, discovery, clinical trials and investments in your AI machine learning capabilities versus say dry powder for investing in external innovation that’d be great.
Marianne De Backer: Yes, I mean, since its inception, Vir has really been a leader in immunology and of course initially focused only on really targeting infectious diseases. But what we are really doing now is broadening that vision to, we call it, powering the immune system, which is really giving patients the ability to empower the immune system to either fight infection, fight cancer. And we do it in two fundamental ways through our powerful antibody therapeutics, which we generate through AI engineering and then secondly, through generating unique T-cell responses in vivo with our T-cell based viral vector platform. So the type of expansion that we are looking at, Alec, is really rooted in our strengths as a company and where we have deep expertise, and that is in immunology, virology and oncology.
So we are looking at expanding into viral associated diseases and then indeed immune targeting, such as in cancer. And we will be sharing more information on our early programs in that area towards the end of the year when we will be holding an R&D Day. So with that, I maybe ask Sung to comment on our cash position and breakdown.
Sung Lee: So with regard to our $1.6 billion in cash and cash equivalent, the majority of this will be dedicated to the ongoing clinical stage programs of hepatitis delta and hepatitis B. Of course, we have to sort of take this one year at a time as we have important data readouts in both of those programs this year. So obviously, we’re rooting for success and that would dictate the capital allocation for subsequent years. But when you look at the immediate year, 2024, we’ve provided guidance, R&D and SG&A expense combined. It’s fair to think that more than half of that is dedicated to the development programs, primarily hepatitis delta and hepatitis B. There’s amounts that will be invested in our antibody platform, and as Marianne said in our prepared comments, will be very opportunistic about tapping into external innovation where it makes sense. But we’ll be very prudent about that.
Operator: Your next question comes from the line of Joseph Stringer with Needham & Company.
Joseph Stringer: Just a follow up question on the delta readout in the second quarter. I wanted to focus on the cirrhotic patients. Clearly, safety will be key. But do you anticipate that it would be more challenging to show a treatment effect in these patients relative to the non-cirrhotic patients? And how important from a commercial perspective would it be to show a clinical effect in these patients?
Phil Pang: I’ll take that one, if that’s all right Marianne. So in terms of cirrhosis, first off, I want to just provide a little clarity. We need to distinguish between patients who we have, who have what we call compensated cirrhosis and patients who have decompensated cirrhosis. Decompensated patients are obviously much more fragile and have a high one year mortality. So I think really we need to — we are focused on getting our drugs to patients as fast as possible, our drug candidates to patients as fast as possible, and that will include both compensated cirrhosis, patients with compensated cirrhosis, as well as those who are non-cirrhotic. We think that the — as I said earlier, I think the compensated cirrhosis patients are approximately 30 to 50% of patients currently living with hepatitis delta.
