Vir Biotechnology, Inc. (VIR) Earnings Call Transcript & Summary

Welcome, everyone, to the 39th Annual JPMorgan Healthcare Conference. My name is Anupam Rama. I'm one of the senior biotech analysts here at JPMorgan. I'm joined by Matt Bannon and Tessa Romero from the team. Our next presenting company is Vir. Presenting on behalf of the company, we have CEO, George Scangos. Before I turn it over to George, I just wanted to highlight for those listeners on the webcast, if you'd like to ask a question, please submit the question via the Ask the Question feature in the portal, and I'm happy to ask the question on your behalf. With that, I'll pass it over to George.

Okay. Thanks, Anupam, and hello, everybody. I'm very, actually, very excited today to be here to give you an update on all the progress that we've made at Vir. Before I dive into that, if we can go to Slide 2. This is the legal disclaimer. So of course, we'll be talking about things today that we expect to happen in the future, things that we expect to happen may not happen. So there's risk. And for a full description of the risks, please see our website and our regulatory filings. If we go to Slide 3, we get to the meat of the presentation here. I think it's important to recognize Vir is only 4 years old as a company. Four years ago today, there were 4 of us sitting around a table in a borrowed conference room, dreaming about the company that we wanted to build. So now if we forward -- fast forward 4 years later, I think everybody at Vir should feel pretty good about what we've accomplished. We have assembled a series of technologies that we believe are really best-in-class. The antibody capability that we have is quite remarkable. Obviously, easy to isolate antibodies from recovered patients, lots of companies can do that, but you do it with various levels of sophistication. And the people doing this at Vir have done this repeatedly and been able to find antibodies that other companies have not been able to find. That was first shown in Ebola, where the single antibody that was isolated is as effective as a cocktail of 3 antibodies from Regeneron. Those are both approved drugs now for their treatment of Ebola. In flu, where we now have multiple pan flu antibodies that other companies have looked for, been unable to find. And as I'll talk to you later in the presentation, it's true for COVID and it's true for hepatitis B. We have -- I think the state-of-the-art siRNA technology. This is Alnylam's technology, not anything that Vir is about. But through a collaboration with Alnylam, we are bringing forward the siRNA for hepatitis B, and we have the rights to additional programs in infectious disease as well. This programmable T cell vaccine system that we have using cytomegalovirus as a vector to induce immunity, and in this case, the HIV and then to TB. This is a program supported by the Gates Foundation that it has generated remarkable data as potentially a transformable way to think about community. And then what we haven't talked about very much is our functional genomics program. Function of Genomics is an incredibly powerful technology these days that is going to fundamentally change the way drugs are discovered. It's going to decrease the failure rate, decrease -- increase the efficacy rate. I think we are one of the leading companies doing this, and we're very excited about that. All those technologies aren't worth anything if you don't execute, and I think our track record now is substantial from 4 years to where we are today with multiple late- and mid-stage compounds in the clinic. I think it's pretty remarkable, and you can see on this slide in any of the events. But if we go into a little more detail, and we go to the next slide, which is Slide 4, a little more detail on what we accomplished in 2020. So we started out the year with the emerging COVID pandemic insight. We took some time. We isolated antibodies against COVID. Let me say that we have many antibodies that look just like the antibodies from other companies, Regeneron, Lilly, AstraZeneca. We did not think those antibodies were the best way to control the virus, and so we took some time to find an antibody that has some unique properties that I'll talk about in a few minutes. We have those antibodies manufactured. We started the clinical programs. We're now in 2 Phase III trials. We established a collaboration with GSK. We did all of that while we kept our other programs going. We established proof-of-concept for hepatitis B siRNA. We started the proof-of-concept trial for 3434, which is our S-antigen antibody targeted against hepatitis B that has the potential to elicit a T cell response and immunity against hep B. And we started our first combination trial of the siRNA together with interferon. We initiated a first Phase I trial for our CMV vector program, carrying an HIV insert. We completed the Phase I study for flu. We confirm the half-life of flu is sufficient so that a single shot should be able to confirm immunity for the entire flu season. And frankly, the only reason that program is not already in a Phase II program is there's no flu during the COVID pandemic. But we're ready to go next fall once people are vaccinated, COVID starts to receive, social distancing stops being quite so extreme. We expect flu to come roaring back, and we'll need that compound. 2021 is likely to be a more -- even a more exciting year than 2020 was. We have the potential now. We're going to get Phase III data on 2 trials of our COVID antibodies. Should those antibodies generate positive data, we will certainly seek regulatory approval and begin selling them. We -- I believe this year will demonstrate or be able to demonstrate whether or not our antibodies that are designed to elicit T cell immunity actually do so in humans, like they do in animals. We'll have meaningful data coming for multiple trials in hepatitis B as well as initiating new studies. What's exciting for us is the combination of our 2218, our siRNA, together with our antibody. And of course, this morning, we announced the initiation of our collaboration with Gilead that I'll talk about it a little more later on, and all of that, while we bring forward flu and HIV program. So this is a year where we have substantial readouts, substantial potential value drivers and the potential to actually become a revenue-generating company. So this is quite an exciting year for us at Vir. This is a snapshot of our clinical pipeline. There are 9 trials on here. That's a lot for a company of our size. And I think notably, there are 6 distinct proprietary compounds on this pipeline. This is not a case where we have 1 or 2 assets that we are exploring in many different indications as there are 6 different proprietary molecules, 4 different diseases. And so we think we are in quite an exciting place with a robust pipeline. We have a robust research pipeline coming behind this. And so we are looking forward not only to this year, but to future years as well. If we now go to Slide 7 and turn attention to COVID. Let me go into the COVID program in a little more detail now. I don't need to reiterate the statistics on COVID. They basically get worse every day. We are fortunate that the RNA vaccines seem to be working so well and have a 95% efficacy. But those vaccines by themselves are unlikely to be sufficient to control COVID over the long term. Herd immunity will take time. It's likely that you will have to get to about 75% of the population vaccinated before we get herd immunity. I don't know if we can achieve that goal at all, given the resistance to vaccination among a substantial fraction of the population in the U.S. And even if we do achieve that, as you've all heard about the virus is mutating, new variants are arising every day. I heard this morning that BioNTech and Pfizer believe their vaccine will be effective against the South African variant. I think that's great news. We should all be happy about that. Two things to remember. Number one, it's likely to be effective, but we don't know if it will be 95% effective or if its ability to reduce infections by certain strains will be reduced somewhat. Hopefully not, but I think the jury is still out. And if we go into the next slide, I think we can see that these variants -- this is Slide 8, that the variants that currently exist are really the tip of the iceberg. The South African variant is scary. There are other variants as well. But these -- there -- although there are 300,000 variants of COVID that have been sequenced, that's a huge number of sequences, that's less than 0.5% of the number of people who've been infected. So guaranteed, there are variants that are circulating that have not been identified. This is exacerbated by the fact that most of the sequences come from 4 countries, almost half from the U.K. alone, then the U.S., Denmark and Australia contributing to the sequencing. But if you think about what's going on in Russia or Eastern Europe or South America or India, a huge amounts of people infected, basically no sequence data coming out of those regions. There must be variants that are circulating that we haven't identified yet. And the virus is not yet under selective pressure. As more and more people get vaccinated and the virus starts to encounter people who are now resistant, that's when the selective pressure on the virus to mutate even more will become evident. And then we'll truly see how plastic this virus is and whether or not -- and how close it gets to flu, which is pretty much able to escape previously existing immunity. Hopefully, that's not the case, but I think, again, the jury is still out. This is a particular problem for monoclonal antibodies, which recognize a specific epitope, a specific region of the virus. If that region is changed in a variant, then the antibodies are likely not to work against that variant. The antibodies for most companies are being -- that are in development are directed towards a region of the virus called the receptor-binding motif, the RBM, that is a highly variable region of the virus. We've already seen this morning, Lilly's antibodies, as according to Lilly, are likely to lose activity against the South African variant. From the sequence we can tell, it is like that one of Regeneron's antibodies will be inactive against that South African variant. There are other variants that are circulating, and we'll get to in a minute. And all of this has led to speculation, which is on Slide 9, that the antibodies might lose efficacy against some of these strains. So Scott Gottlieb said that it appears that the South African variant seems to obviate antibody drugs. Tony Fauci was a little more measured. It might have some negative impact on the efficacy of some of the monoclonal antibodies used. So what does this mean for Vir and Vir's antibodies? And that's on the next slide, this is Slide 10. So we look here at 4 variants that are circulating and increasing in prevalence. There's a South African mutant, the U.K. mutant, both of those have gotten a lot of press. There's also a mutant that arose in Scotland that now has spread to many other countries and a mutant that came out of the mink infections that occurred in Denmark. All of these mutations become refractory to one or both of the antibodies in the competitors' cocktail. All of these variants are expected to be inhibited by 7831. We fully expect 7831 to retain activity against all of these variants. And that is because the epitope, the region of the virus to which 7831 binds is unchanged in all of these variants. And the hypothesis and the rationale that we've used that we've been saying for months that a single antibody against a highly conserved region of the virus will be a more effective way to deal with mutants innovation than a cocktail of 2 antibodies against region that is easily changed seems to be playing out. And so we are pretty excited about the potential for our antibody and continued activity against not only the current strains, but hopefully future strains as well. That resistant, the ability to deal with multiple strains is not the only characteristic that's important to antibodies. So if we go to Slide 11, you can see we have recent publications here describing a second property of antibodies that is essential for maximizing therapeutic efficacy against COVID. And that is the ability of the antibodies to recruit cells of the immune system, to kill cells that are already infected. So all of the antibodies, ours and all of the antibodies from other companies potently neutralize the virus. That means they bind to the virus and prevent its ability to infect new cells. Some antibodies have a second property, which is that they can lead to the killing of cells that are already infected. And these are 2 papers here recently from academic groups, independent, to say that, that second property, the ability to kill infected cells is really important to maximize therapeutic efficacy. Doesn't matter much for prophylaxis, but it really matters for therapy. It makes sense that in an infected person, you not only have to block the new -- infection of new cells, but you actually need to block those that -- kill those all factories that are making millions of new viruses, which is a constant challenge for the drugs to block. So 7831, our antibody, is -- has potent activity in being able to kill cells that are already infected in contrast to the antibodies being developed by other companies, which either have none of that activity at all or much less potent activity in this regard. So we believe that 7831 has additional advantages in this characteristic. This is all summarized on Page 12. We see the characteristics of our antibody, which is potent in neutralizing antibody, blocks viral entry into healthy cells. It clears the infection by killing cells that are already infected. It has a high barrier to resistance that retains activity. It's likely to retain activity against all the variants that are circulating. We have a low dose. We have a 500-milligram dose that it lends itself to administration through an IM route rather than IV infusion as opposed to the multi gram doses being developed by other companies. We have extended the half-life and that same alteration that extends a half-life leads to increased bioavailability in the lung. So all of these characteristics make us believe that we have a best-in-class antibody here that can provide substantial benefit for patients. So obviously testing that aggressively and the clinical programs are outlined on Slide 13. And we have the COMET-ICE study, which is our study that we're conducting in patients at high-risk of hospitalization. These are infected patients, outpatients at high risk. The endpoint is a hard endpoint, reduction in hospitalization, reduction in death. We'll get Phase III data very soon now. The NIH study, ACTIV-3, which is being conducted in hospitalized patients. This is the same study in which Lilly's antibody did not pass the interim analysis. We believe that our ability that 7831 has to kill already infected cells and have additional potency in the therapeutic setting gives us a possibility of providing the benefit to those patients. We will get that same endpoint also very soon now. [indiscernible] is our study that will soon start for prophylaxis. And then the AGILE study, which we announced this morning, AGILE is the U.K. group that's kind of analogous to active in the U.S. They're going to test our antibody 7832, which is designed to have even more potent ability to kill infected cells and to induce a T cell response. So this antibody has the potential not only to be a potent therapeutic but to induce in those patients long-lasting T cell immunity, so to be acted as both a vaccine and therapeutic antibody. The animal data suggests that it has that activity, and we'll be able to see whether or not the human immune system reacts in the same way, and we're able to fundamentally transform the way we think about using antibodies. All of this is done in collaboration with GSK, and that's on Slide 14. This is a wonderful partnership. GSK has been, I have to say, a great partner. In all my years in the industry, this is probably the best collaboration between a small biotech and a large pharma company that I've seen. GSK has accelerated the development of the antibodies. They've truly worked for win-win situations. They move quickly. They have great science. They have a lot of respect for their scientists. I think that's mutual. And the antibodies have been substantially helped by the collaboration with GSK. We're also working with GSK on the development of pan-coronavirus small molecules and on pan-coronavirus vaccines. We've heard a lot about the RNA vaccines now that are so exciting and rapid that maybe in the next coronavirus outbreak, the next pandemic, we could rapidly make the RNA vaccines and react quickly. But in my view, it's much better to now develop reagents that are pan-coronavirus. And for example, pan-coronavirus vaccine, we can then immunize the population. And rather than having to react the next epidemic, we can prevent the next epidemic. So we're pretty excited. We made great progress in both of these. We're pretty excited about that coming forward as well. Turn to now Slide 15 to just turn our attention briefly to HBV. Our strategy here has been twofold, to reduce the level of circulating HBV proteins which suppress the immune system and then to stimulate the immune system to regain control of the viral infection and lead to a functional cure. We have 2 proprietary assets, our siRNA 2218 in combination with Alnylam, and Alnylam has also been a really good partner here, and then 3434, which is a very unique antibody that is a potent inhibitor of [Audio Gap] entry. It removes the tolerogens and allows the immune system to recover, and it actually has the same alteration that we hope will lead to the stimulation of a T cell response that can bring the infection under control. We have a very broad program now. This is on the left -- this is Slide 16. On the left, you see data from 2218, our siRNA [Audio Gap] these are old data, shows a dose-dependent decline in S-antigen after application of the siRNA. That siRNA is now currently in a Phase II trial in combination with PEG interferon. We will have data this year. Our antibody 3434 is currently in a single-agent study. We'll have data for that this year, and we will start the combination of 2218 and 3434. We announced this morning a collaboration with Gilead to test 2218 in combination with their TLR8 agonist and nivolumab. That clinical trial will start this year. That's a very interesting collaboration with Gilead. We agreed to test our molecules in combination with each other. We have not granted Gilead any rights to 2218. They have not granted us rights to their TLR8 agonist. Should this trial generate positive data, we'll discuss with Gilead ways to go forward together, but neither company has an obligation to do so. And then our partner, Brii in China is starting a Phase II study of 2218 in combination with the T cell vaccine. So we've managed, as a small company, to put together a broad portfolio of HBV programs that is one of the leading programs in the industry now, while we and Alnylam have retained the ownership of 2218. So we're very excited about these data. We think there's high potential here to lead to a functional cure for hepatitis B. Doesn't get as much attention these days because of all the focus on COVID. But in the long run, we think this is an incredibly valuable and important program. Switch gears a little bit. Slide 17 is our flu program. Just to remind everybody, we have an antibody that covers all strains of flu A that have arisen since the 1918 pandemic. This antibody has been through Phase I -- been through Phase I. We are developing it as a prophylactic antibody for patients at high-risk of hospitalization. There are millions of those patients in the U.S. And it overcomes the limitations to the vaccine, and that is passive. It doesn't depend on the host system to -- for immunity and it's pan-flu, so you don't have to guess the strains that are circulating. We intend to start a Phase II trial for this or expect to start a Phase II trial for this in the fourth quarter of this year on next fall's flu season. Finally, we have a T cell platform. This is using CMV as a vector to elicit potent T cell responses against inserts in [Audio Gap] We've now dosed our first patients with the CMV vector carrying an HIV insert. This is potentially transformative and a way to generate effective vaccines against pathogens like HIV that have been really refractory to the development of vaccines. Just to remind you all, the same system developed really potent immunity in monkeys, primates against simian immunodeficiency virus, actually somewhat more aggressive form of HIV that circulates in monkeys, and it protected them against TB as well. So we will have data to -- this year to test whether the human immune system is reacting in the same way that the primate immune systems reacted to. So pretty excited about that. Lots of catalysts coming up this year. I'm not going to go through all these. These will be posted on our website. You can take your time and go through these if you're interested. But just to size, we have really meaningful value drivers, really meaningful events for our company and for patients coming up this year. Not only will we have the 2 Phase III readouts for our COVID antibodies, if positive, we'll certainly seek approval and launch. We'll have important Phase II readouts for multiple trials in hepatitis B and our search for a functional cure for hepatitis B. We will have proof of biology data for our HIV vaccine system for vaccinal antibodies. We will bring forward multi-pathogen targeted small molecules and we have many more molecules coming out of our research. So here, our mission is to create a world without infectious disease. I don't think we're going to achieve that during 2021, but I think we have a good chance to make a lot of progress towards that goal. So thank you all for your attention, and we'll stop now and open it up for questions.

Okay. Thanks for that, George. We will just throw a reminder out there that if you want to ask a question via the portal, just submit it, and I'm happy to ask on your behalf. George, if you want to just quickly introduce the broader team on the line, we can get started.

Sure. Yes. I'm now joined by several members of our team. We have Howard Horn, who's our CFO; Phil Pang, who's our Chief Medical Officer; Bolyn Hubby, our Chief Corporate Affairs Officer; and Neera Ravindran, who heads Investor Relations for Vir. Any tough questions, I'm going to throw out to one of those.

Okay. We've got our first question actually from the poll, which is assuming the antibody -- your COVID antibody, it works and is approved in 2021 under an EUA. How many courses will you be able to get to patients in 2021 and 2022? And what settings do you think you'll be able to administer them?

Look, that's a great question. It's a multi-part question. In terms of the number of doses, we think this year we'll have a couple of million available over the course of 2021, many more than that in 2022. So substantial number of doses this year. I think the question refers to the fact that the IV administration of these antibodies has limited their utilization so far. And we've all read the reports that the antibodies aren't being used as widely as expected because of that. I think this is also because of the fact that the data so far which are convincing to me aren't convincing to a lot of clinicians because the number of patients in those databases is so small. So data that's viewed as not compelling together with the inconvenience of having to administer [Audio Gap] use. Our trial that we're doing, I think it's important to know. We are doing fundamentally different clinical strategy from Regeneron and Gilead. They did early studies on a small number of patients to get quick data and appropriately so. So I'm not saying that are at all to be critical, I think, [Audio Gap] thing for them to do. We took a different approach. We did not do a small Phase I/II study. We jumped into Phase III. We already have many more patients dosed than they had when they reported their first data. So the data that we expect to report, a robust data in a Phase III trial designed to be sufficient not just for an EUA, but for a full out approval. So we'll have -- I think we should overcome if the data are positive, the hesitancy based on limited data. And secondly, we have a dose, 500 milligrams we can administer IM, and we are rapidly working on a formulation now to switch from the IV dosing, which we're using a clinical trial to be able to administer the drug by IM. So if -- once that succeeds and is available, we would anticipate much wider use of the antibodies.

We've got another question in the portal here just related to your cash position and burn in 2021.

Howard, isn't that a question for you?

All right. I'll take it. So we have -- at the end of the third quarter, we had $837 million in cash. And at the time in our filings what we said is that would give us runway for the next 12 months, that was in November of last year. And today, at this time, we're not updating that. We're not reconfirming that, but those are the facts.

And then maybe I'll hop in with a question here on 7831. I think the prior guidance for COMET-ICE had suggested data could come as early as January, but the guidance I think in the slides today is more broadly 1Q '21. Like how do we think about that? And then, I guess, given what we know about the COVID antibodies from Lilly and Regeneron, what's kind of a win scenario on some of the key endpoints for you guys? One -- and I will say one of the pushbacks we got on our preview note for COMET-ICE was we said, "Hey, maybe the appropriate competitor here is Lilly monotherapy, but I think maybe there's an expectation on the street about perhaps Lilly combo might be the better competitor." Maybe you could address some of those questions?

Yes. Look, I think there are a number of ways to think about that. Look, in terms of timing, where we are enrolling really quickly, we -- there are several analyses going on. So it's possible we'll have data this month, it's possible we'll have data later in the quarter. So it's a little hard to be more specific about the timing. In terms of the bar, there are multiple aspects. Look, in terms of reduction of the rate of hospitalization in the outpatients, we need to be competitive or better with -- than the combination of Lilly and Regeneron's antibodies. So I think that's fair. In terms of resistance, I mean, Lilly with our monotherapy saw a number of resistant muteness arising during the course of the trial. We would expect not to see that. And so in the outpatient setting, we would expect and hope to be at least as good as the combination. And remember, we have a single antibody but we have a really potent effector function. We believe that second property is very important for maximizing therapeutic efficacy. So we believe there's a chance we can be at least as good and potentially better. In the hospital setting, Lilly's antibodies did not pass the interim analysis in the active trial. So the first barrier for us is passing the interim analysis, right? And we'll see. That should be coming up also pretty soon. The trial is actively enrolling now. Look, that's a tougher population. Antibodies have a harder time working there. I'm sure all drugs have a harder time working later in the disease. So I don't know what to expect there, but I think the added ability to kill the already-infected cells gives us a chance of succeeding there, which would obviously be kind of a home run if that were to be the case.

We've got another question from the e-mail portal here. Kind of on your prior comments, maybe expanding a little bit, question is basically Regeneron and Lilly have run into manufacturing issues and are unable to supply the current market. How many doses do you think you'll be able to supply immediately upon approval?

Neera, I have to check with you. I don't know what we've said publicly here. So are we...

We've said several million within the first year after approval.

Yes. But we haven't been more granular than that.

Yes.

Yes. Okay. So let's not go there. Look, we are -- there is an issue with making in-buys, right? It's expensive. It takes a long time. There's limited capacity. So we have a manufacturing agreement with WuXi in China that are cranking out antibody as fast as they can right now. We have an agreement with Samsung that will come online and make antibodies [Audio Gap] as well. And so we are gearing up to be able to have tens of millions of doses or let's say 10 million doses annually. We will get there in 2022 and we'll be well on our way there in 2021, that we can over the course of the year, to be clear.

Yes. I think Matt, from the team. He's got a question?

Yes. It's -- my question is related, and it's ultimately on the size of the therapeutic market in COVID-19. So I guess, like it's kind of easy to identify the high level push-pull factors, vaccination rates, vaccination efficacy and whatnot, but it gets a little trickier when you consider the new strains, the new variants. So just to think if you could lay out sort of your framework for how you think about that, that might be helpful.

Yes. I think -- look, I think that is one of the key advantages that we think we have. And that based on the sequence stated, we expect our antibody to retain activity against all of the current variants. South Africa and U.K., Scottish mink, and probably against many of variants that will arise in the future. So we have an advantage there. And as those strains become more prevalent, you saw in one of the slides is those strains now represent about almost 25% of all of the sequences. So those strains are increasing in prevalence, they probably will take over. So the inability to inhibit those strains will severely limit the use of the antibodies over time. And that's why we are -- one of the reasons we're feeling good about 7831, which retains activity. The shape of the pandemic, how well the vaccines work, how fast they can be rolled out, how many people take them, obviously, will impact the need for the antibodies. In an ideal world, and I mean this sincerely, we'd all get vaccinated tomorrow, we would not need antibodies and COVID would go away. I just don't think that's going to happen. And I'm shocked to read about the number of first-line health care workers who are reluctant to take the vaccine. Those should be educated people in great need of the vaccine. When we got out into the general population, I'm not sure if we can vaccinate enough people to generate true herd immunity. I'm also not -- it's great to have a 95% effective vaccine. Suppose the vaccines are 70% effective against the South African strain, they still work, they still provide protection but not quite as well. That means the barrier for herd immunity [indiscernible] even further. So I think in most plausible scenarios, there will be a major need for antibodies for several years to come. And it has been a combination of vaccines and antibodies and other drugs, probably with small molecules coming, that will be able to attenuate the worst outcomes in people who are infected. And the combination of those is what's going to be needed to get us back to normal.

Maybe I'll ask a final question here. It turns out you guys have programs that are not just COVID. So just on 2281 and the deal announced this morning. I guess what struck me there is, how you're thinking about strategically 2218 and the development path, right? Because you've got internal assets that you could go combination with like 3434. You now have the -- you've shown us the potential to go maybe externally for collaborations to kind of maximize your HBV franchise. How do you think about sort of prioritizing sort of internal and external joint ventures?

Yes. That's a really interesting question. Look, we're a small company. We are competing hepatitis B with much larger companies, Roche, J&J, GSK. And we believe that 2218, the siRNAs, number one, can be a fundamental part of a functional cure for hepatitis B. We think our siRNA has the potential to be the best-in-class. Frankly, if you look at ours compared to the Arrowhead 1 that's now with J&J or the Dicerna 1 that's now with Roche, hard to see a difference in efficacy. I think we have very clean data showing dose responsiveness. But the toxicity of siRNA results largely from off-target activity. And I think Alnylam's technology, where they call this ESC+ technology gives a substantially -- and we know that it has substantially reduced off-target activity and potentially less toxicity. So the question for us is how do we generate a broad program? We've got siRNA, 3434, we believe has great utility as a very exciting asset, but we want to test multiple mechanisms to see if we can get to a therapy that is effective for the largest number of patients. Gilead is obviously a really experienced country with -- company with great assets of their own. And so we -- I think is this collaboration is a great one, and that it allows us to test a pretty interesting new combination without having to sign an agreement that, although it might bring in a lot of cash in the near term, gives away a lot of the value of 2218 in the long term. We want to retain that long-term value. And so I think that's the strategy. We will -- happy to collaborate, happy to expand the program, but we are not excited about reverting to a royalty structure and return for a lot of upfront cash.

Understood. George and team, I want to thank you guys so much for participating in a really, really productive session. Thank you guys so much, and I hope you guys have a great rest of the conference.

Okay. Thank you, Anupam. Appreciate it.

Thank you, guys.