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Most of us have heard about hepatitis b and how in its final stages, it can lead to liver failure, cirrhosis of the liver, or liver cancer. More serious still are actually 2 viruses together, hepatitis b and hepatitis d, d as in delta. In combination, there is no standard of care in the US. Doctor Marianne De Backer, the CEO of Vir Biotechnology, joins me to talk about their approach and a preliminary
Dr. Moira Gunn:readout from their phase 2 clinical trials. Doctor De Backer, welcome back to Biotechnation.
Dr. Marianne De Backer:Thank you, Moira. A pleasure to be here again.
Dr. Moira Gunn:Now Vir Biotechnology has a very wide portfolio of efforts across the infectious disease spectrum with a particular emphasis in viruses, viruses that cause disease. And I wanna focus on 1 of your efforts today. And that has to do with 2 viruses that which when they get together are extremely serious. Now most of us have heard of hepatitis b and according to the CDC, there are over 1, 600, 000 cases of hepatitis b in the United States alone and this virus attacks the liver. But of those cases, some 30, 000 patients in the United States have acquired either at the same time or later a second virus, hepatitis d or as it's often called, hepatitis delta.
Dr. Moira Gunn:What happens when a person carries both viruses, hep b and hep d? How serious is it?
Dr. Marianne De Backer:Yes, Moira. So people might not think of it, but actually the leading cause of liver cancer is viral hepatitis. So really, our liver cells being infected by viruses. And you have hepatitis a, hepatitis b, hepatitis C, and as you point out, also hepatitis D or Delta. And the very unique thing is that hepatitis delta virus is so tiny that it isn't actually capable of replicating on its own.
Dr. Marianne De Backer:It needs hepatitis b to do so. So it really hijacks another virus in order to be able to sustain itself. And unfortunately, for patients that are infected with both viruses, both hepatitis b and delta, and the estimation actually for the United States is that might be about a 100, 000 people. The the progression to liver disease is, and to liver cancer is actually 4 times faster if you are coinfected. You also progress, actually, unfortunately, 2 times faster to mortality.
Dr. Marianne De Backer:And, you know, if you're infected with hepatitis delta, more than 50% of the patients actually die within a brief period of 10 years.
Dr. Moira Gunn:Now if you have both hepatitis b and d, what treatment options do you have specific to that?
Dr. Marianne De Backer:Yes. Unfortunately, here in United States, there is absolutely nothing available. So if you are diagnosed tomorrow with a hepatitis delta infection, there's very little that physicians can do. So the unmet need is is truly very high.
Dr. Moira Gunn:So in 1 of your programs, Vir is well into clinical trials with 2 drugs and with some success, which we'll get to. But let's start with what these 2 drugs do. What do they do?
Dr. Marianne De Backer:Yes. So, we have a 2 part drug, if you will. So it consists of, on the 1 hand, an antibody that we call 2bivibard. And what that antibody does, in essence, it prevents the virus from getting inside the liver cell, which is, of course, very important because then it can't infect the cell. And it also helps the body to really fight the virus.
Dr. Marianne De Backer:So that's 1 part of the of the treatment regimen. The other part of the treatment regimen is what we call an siRNA, a small inhibitory RNA, with the name of elapsiran. And, that really stops the virus basically from making copies of itself. So it dices up, or it cuts up the instructions to do so, and it prevents the virus from really, really replicating.
Dr. Moira Gunn:So you've got 2 parts here. 2 drugs, and they work together.
Dr. Marianne De Backer:Correct. Yes. They are complementary in the way that they work. Mhmm.
Dr. Moira Gunn:Now that brings us to your clinical trials. You've already established that both drugs are safe in humans and and now you're well into phase 2 and are testing both. How have you structured phase 2? Who are the participants? How do they take these drugs?
Dr. Marianne De Backer:Yes. So we are in our Solstice trial evaluating either, the efficacy, safety, and tolerability of our antibody alone, or the combination of the antibody with the siRNA. So the cutting, cutting drug. So we enrolled, 2 cohorts, 1 cohort of about 30 participants that are delta patients that will be getting the antibody every 2 weeks. And about half of those patients are actually people with early cirrhosis, so with early liver damage.
Dr. Marianne De Backer:Because as we discussed a little earlier, patients with delta infection progress to liver damage very, very quickly. So, it's really important to study the drug in patients that already have early onset of liver damage. Our other cohort is then evaluating the combination of our antibody and siRNA, which is basically a monthly administration. And again, also in that cohort, we have both patients that are non cirrhotic, and patients that already have cirrhosis. And it's about a 5050, you know, as it relates to to those kind of participants.
Dr. Moira Gunn:So for people with cirrhosis of the liver, they have really progressed now. That is a very dangerous place to be.
Dr. Marianne De Backer:Yes. So what we have the the types of patients that we have included in our trial have early stages of cirrhosis, so certainly not end stage. But, again, the progression of disease is very fast, and so it's really important that we can demonstrate that our, our potential medicines would also work in patients that, have cirrhosis. Because remember, Moira, this is a disease that typically gets diagnosed very late. You basically have no symptoms for the longest time.
Dr. Marianne De Backer:That's why, you know, hepatitis delta is called a silent killer. So patients don't really have any symptoms for the longest time. And then suddenly, you know, the liver damage has progressed to a point where they go and see a physician. And often, you know, patients are then already so far progressed that they need to, consider a liver transplant. So, diagnosis is certainly a really big problem for this disease and needs to improve.
Dr. Marianne De Backer:But, again, it's really important to also look in patients that have already some liver damage.
Dr. Moira Gunn:Now many people think that you wait until the very end of a trial to get any results at all. And we're sort of midway through this phase 2 trial, and you've already gotten some results. What have you learned?
Dr. Marianne De Backer:Yes. That is correct. We have, preliminary data from treating, patients with 12 weeks or 24 weeks, with both, with both, drug combinations. And we learned, actually, from the preliminary data that we do well with antibody alone, but even better when you combine the 2 together. So when you combine the antibody with the siRNA together.
Dr. Marianne De Backer:And so, basically, what you look at in these kind of trials, Maura, and and again, it's the holy grail of any viral disease, is is seeing do you really get rid of the virus? In the end, that's, you know, that's your end goal. That's what you want to achieve. So and the way we do that is, as I mentioned, delta is a tiny virus. It's an RNA virus.
Dr. Marianne De Backer:And so you can really take blood from patients and look at how much virus is remaining in in the serum of patients. And when you do so, there's a number of different ways to do it. You can look at the lower level of quantification, which means that, you know, there's still, a little bit of virus there. So just enough to be able to quantify it. And you can also look at what we call target not detected.
Dr. Marianne De Backer:Which means that, in that case, the viral RNA has entirely disappeared, and you can't, you know, detect any anymore. So, if you take those 2 measurements, when you look at our combination therapies of the antibody and s iRNA together, after 24 weeks of treatment, so that's only 6 doses of of therapy, we saw in 11 participants that, all of them, 100% of the participant had reached delta RNA levels that were below that lower limit of quantification. And more than 50% of the patients had what we call, as I just mentioned, target not detected. So, we could not detect the virus in their blood any longer. So, you know, again, preliminary data and a small, cohort of participants, but very impressive, readouts.
Dr. Marianne De Backer:Now, beyond just looking at, you know, the virus and has the virus disappeared, 1 of the regulatory requirements is also to look at what is called ALT normalization. And, basically, what happens if your liver gets damaged, you have ALT or an enzyme, of, you know, something that a substance that gets released in your blood, and you can measure it. And so it's basically a measurement for the amount of damage that your your your liver is undergoing. And 1 of the requirements from the regulators at this moment in time, is that in addition to showing, you know, impact on the virus, you also show that your ALT levels go back to a normal range. So, again, as a substitute or biomarker, if you will, for, you know, improving liver health.
Dr. Moira Gunn:Now is that the same ALT recording you see when you go annually or whenever you go to the doctor and they take all of this blood for you, 1 file after another, and they say look at look at everything here. I know with the liver, it has ALT. Is that the same measurement?
Dr. Marianne De Backer:Absolutely the same. Exactly. And and, you know, you might even, you know, if if you drink a lot of alcohol or even if you very, you know, excessively, exercise, your ALT levels might also increase. But that is typically a very temporary thing. But again, if you have true liver damage, then you have this, you know, sustained higher levels of ALT.
Dr. Marianne De Backer:And, especially in patients, you know, that are infected with hepatitis delta, these levels tend to be very high. And so, again, you know, it's it's a biomarker, it's a substitute for us to look if you give a potential treatment to a patient. Do you actually get to a, again, normal levels of that of that ALT?
Dr. Moira Gunn:And so here we are, preliminary, halfway through, and these are remarkable results. Normally, we say this percentage kinda did better than that percentage, what they did. It's like, this is truly these are remarkable numbers.
Dr. Marianne De Backer:Yes. Yes. Truly very promising. I mean, for again, just after 6 doses at 24 weeks, we, saw 64% of the participants that also got their ALT to normal levels. So, yes.
Dr. Marianne De Backer:Very, very, very promising results. And, you know, the unmet need is so high that, we really hope that, you know, we are on the cusp here of being able to bring a potentially really transformative regimen to patients because, you know, patient patients are truly waiting, for, you know, an option, especially here in the United States.
Dr. Moira Gunn:Now let me ask you this. You were saying we're dosing every 2 weeks or dosing every month. What do you mean by dosing?
Dr. Marianne De Backer:Yes. So, for our antibody alone, we have been, administrating, the, antibody on a biweekly basis. And so, basically, that's, and in sub subcutaneous injection every 2 weeks. And for the combination of the both of the antibody and s iRNA, again, it's a monthly administration of 2 individual subcutaneous injections.
Dr. Moira Gunn:And how long would that take if you go in to get such an injection or injections?
Dr. Marianne De Backer:Yes. I mean, thus far, of course, we're still in a clinical stage, trial setting, so it's a little bit different. But, of course, that doesn't take a very long time. I mean, you know, you would take 15 minutes or so to do to do that. Right?
Dr. Moira Gunn:Okay. So we're in the preliminary stage, and there are as I understand it, you're fully enrolled, but more and more people have to come in as well as people will continue throughout this trial. When do you anticipate its completion?
Dr. Marianne De Backer:Yes. So in the fall, we will have for all of our, approximately 60 participants in the trial, the full 24 week data. So that will be, you know, very exciting for us to see. And the next step, again, you know, the data, again, preliminary, small numbers, but are are looking so promising that we do want to go and engage with the regulators, the FDA, and the EMA, and to have discussions with them, you know, what would be a path to bring this to patients as quickly as possible, and what could a registrational trial look like for for this regimen?
Dr. Moira Gunn:Now, the FDA, of course, covers the United States. The EMA covers it in Europe. What point do you think the earliest is that you might be able to come up with this release?
Dr. Marianne De Backer:Yes. That is always very difficult to predict, Moira. You know.
Dr. Moira Gunn:III just ask the questions. I don't have to answer them.
Dr. Marianne De Backer:Yes. I mean, it will all depend on, you know, how the regulators, see it. And it's a combination, of course, of, unmet need, how strong is your data package, how is the safety and tolerability looking of your of your drugs. So there's a lot of things that play here. But, again, given the unmet need and the strength of the data, our goal is to really apply for every possible acceleration pathway.
Dr. Marianne De Backer:So, be it PRIME in Europe, Fast Track Designation, there's Breakthrough Designation. There's also, as you, you as we discussed in the beginning of of this, call, I mean, the the number of patients in the United States and and in Europe, you know, allow it to potentially be designated as an orphan disease, so we can also, you know, apply for orphan drug designation. So there's a lot of potential avenues here to try and see how we, as quickly as possible, can bring this regimen, hopefully, to patients.
Dr. Moira Gunn:That was a great answer given you didn't give me a time. But I know you're gonna be working on it, and I'll let you off the hook. I know you're working on it fast. That's good. Now what we haven't done is, and have not done justice to is talk about all the work that Veer is doing on a number of virus induced, conditions.
Dr. Moira Gunn:Give us a big picture here about what Vir is doing and and what medical conditions you're working on.
Dr. Marianne De Backer:Yes. So Vir was founded, only 8 years ago, which is, I think quite astonishing. And and already 2 drugs that were discoveries from the labs of Veer have gone all the way to patients. So 1 is an antibody against Ebola, and the other 1 is an antibody against COVID. So I think that's, you know, quite, quite an achievement.
Dr. Marianne De Backer:But, you know, the fundamental the fundamental premise of the company is that we want to give the immune system tools to fight disease. That's basically what we're aiming to achieve. And so that was possible with Ebola, with COVID, we are now making good strides in Hepatitis Delta. So, the next program we're working on is in hepatitis B, which, again, there isn't any cure available for hepatitis B today. So, in hepatitis delta, we're striving for a chronic treatment.
Dr. Marianne De Backer:In hepatitis b, the real unmet need is a cure, a functional cure. So we are working towards a functional cure for hepatitis b. And then, we have a number of programs that are preclinical. We are working on, the RSV virus, we're working on HIV, we're working in influenza. So there's a number of infectious diseases where there's still a lot of, you know, unmet need and progress that could be made.
Dr. Marianne De Backer:And beyond that, Moira, I just want to say that, you know, your immune system doesn't distinguish whether you, you know, in fighting, intrusion or something that is foreign. And whether you're infected by a virus or a cancer cell starts growing in your body, it's it's often how your immune system responds that determines the outcome of disease. So and I think we have such, you know, such an important and powerful technology platforms here that we also want to basically open up our focus, so to speak. And beyond infectious disease, also look at what are other areas where we can deploy these tools and and make patient impact.
Dr. Moira Gunn:Well, doctor Debaca, thank you so much for coming in. And, please come back and and keep us updated.
Dr. Marianne De Backer:Oh, it will be my pleasure. Thank you so much, Mara.
Dr. Moira Gunn:Doctor Marianne De Backer is the CEO of Vir Biotechnology. Since this interview, Vir's combination therapy for hepatitis delta has received fast track designation from the FDA. More information is available on the web@vir.bio. That's veer, virveer.bio.