Good afternoon, and welcome to Assembly Bio's phase II expansion study update webcast and conference call. At this time, all participants are in listen-only mode. Later, we will conduct a question and answer session after the prepared remarks. As a reminder, this conference call is being recorded. I would now like to hand the call over to Lauren Glaser, Senior Vice President of Investor Relations and Corporate Affairs for Assembly Bio. Please go ahead.
Good afternoon, and thank you for joining us as we discuss interim results from Study 211, our phase II extension study monitoring patients with chronic hepatitis B virus for sustained virologic response, or SVR, following discontinuation of treatment with vebicorvir and a nucleoside analog. This afternoon, we issued a press release providing an update on this ongoing study, as well as a second press release reporting our financial results for the third quarter ended September 30th, 2020. These press releases are available in the news and events section of our corporate website at www.assemblybio.com. Please note that a replay of today's call and audio webcast also will be available from our website. In a moment, I will turn the call over to our Chief Executive Officer and President, Dr. John McHutchison, to provide opening remarks, and then we will host a Q&A session.
Joining John for the Q&A portion of the call will be our Chief Medical Officer, Dr. Luisa Stamm, our Chief Scientific Officer of Virology, Dr. Bill Delaney, and our Chief Financial Officer, Tom Russo. Before we begin, I want to remind you that we will be making forward-looking statements, including statements regarding our future research and development plans, evaluation of interim data, the timing of clinical trials, trial results, and therapeutic potential of our development programs. These statements are subject to the Safe Harbor protections provided under the Private Securities Litigation Reform Act of 1995. They involve certain assumptions, risks, and uncertainties that are beyond our control, and actual results may differ materially from these forward-looking statements. A description of these risks can be found in our latest SEC disclosure documents and press releases. Assembly does not undertake any obligation to update any forward-looking statements made during this call.
I'll now hand the call over to our CEO, Dr. John McHutchison.
Thanks, Lauren, and thanks to everyone for joining us today on short notice as well. While we're beginning to analyze the latest Study 211 data, and we don't have many of the answers yet, the study has not achieved a meaningful sustained response rate to date, so we felt it important to now provide you with the update. The study is still ongoing and will continue to collect and analyze data with the goal of informing our development programs in the hepatitis B field generally. We appreciate your patience and expect to submit more detailed results to future scientific meetings as well. What we do know is 39 of 41 hepatitis B patients in Study 211 have now relapsed between the four and 16-week time points following treatment discontinuation.
The study is the first in the hepatitis B field to explore whether a sustained response or SVR could be achieved off therapy with a core inhibitor dual combination regimen. Study 211 patients were virologically suppressed for at least eight, 12-18 months of treatment with our core inhibitor, vebicorvir, and a nucleoside analog or NUC. The patients who met the treatment stopping criteria were withdrawn from therapy and they've been assessed monthly since then for relapse. The study was designed to measure the proportion of patients with SVR off treatment at 24 weeks because this represents an endpoint that allows our regulators to consider an approach to ultimately register a drug regimen as a finite therapy for patients with hepatitis B.
As we mentioned in our press release, 22 of the 23 patients with e-antigen negative hepatitis B have relapsed, which is defined as off-treatment quantifiable DNA by the cobas assay with a low limit of quantification of 20 international units for an SVR 4 rate of 4% at the last visit. 16 of these patients first relapsed at post-treatment week four, but six relapsed also at post-treatment week 12 or 16. If we look at the e-antigen positive patients, 17 of 18 have relapsed at post-treatment week four for an SVR rate of 6% at the last visit. In terms of SVR, the focus of this experiment, our hope, as I have said, had been that we might see at least 15%, a percentage that would have marked a significant first advance towards a potential hepatitis B finite therapy.
These results, as I've described them today, have shown us that we fall short of this mark. I'm sure you all have many questions about what we should and what we might glean from the data, as do we, and we'll be continuing our analyses in the coming weeks and as further data are collected in the study. Specifically, we'll look to understand all we can, given the relatively small sample size, and this will include subgroup analyses of the populations of patients who initially achieved an early SVR from those that did not, as well as the timing of the relapse with regard to the demographics, the disease characteristics, and of course, our laboratory assessments with our more sensitive assays as well.
It's important to note that the study was the first of its kind involving core inhibitors. It's one of the many steps on the path to transform hepatitis B treatment from currently its lifelong therapy. Firstly, by delivering a more effective chronic suppressive therapy, in particular, addressing the unmet need, a full viral suppression for the estimated 10%-30% of patients who don't achieve that on a NUC alone. We'll talk about this in a little while. Eventually, of course, to the ultimate goal of finite therapies and then the cure or the functional cure of hepatitis B. If we look back at how the treatment landscape evolved for HIV and hepatitis C, there were many disappointments before we started seeing the major leaps forward in efficacy and ultimately all those successful regimens.
Bill Delaney and I were just recalling the other day one of the combination therapy approaches with multiple phase II studies we ran for hepatitis C, combining three distinct oral antivirals with interferon. While the results of this approach were disappointing in terms of the SVR rate and also resistance, the study provided important information, or those studies provided important information that helped us push on. Ultimately, we learned from that and remained sort of relentless in our efforts to drive the field forward to develop new treatment options for those patients with hep C. With that experience and our collective resilience in mind, the detailed analyses we'll conduct on Study 211 may give us some insight for future study designs, such as whether a longer period or treatment duration, different or more stringent stopping criteria, focusing on specific subpopulations might increase the potential for sustained responses off treatment.
This all remains to be seen, of course. In many ways, Hep B is more challenging than hepatitis C. The task will be harder, as I've said from day one here, really, and the progress will be incremental. I'm confident that an experienced team like ours will get there over time. We are in this for the long run. When I joined the company a little over a year ago, I outlined what I believed were the waves of development that the company would frame our approach to hepatitis B upon, and that included four distinct and parallel strategies to advance our pipeline of core inhibitors. Even with today's setback, three of those four strategies remain on track. Fortunately, as a company, we are well-positioned to continue to advance them and are already doing so in important ways, which I will now describe.
Our first strategy has always been to deliver a better chronic suppressive therapy. We have already shown in our phase II trial, Study 201 and 202, that the addition of vebicorvir to NUC therapy can achieve a more rapid and complete level of viral suppression than seen with NUCs alone and with a similar safety and tolerability profile. These data form the basis for our intended phase III registrational program for vebicorvir plus a NUC as better chronic suppressive therapy. We plan to include multiple patient populations in the phase III registrational program and for it to be conducted globally and in China with our partner, BeiGene. One of the two populations we plan to include is the partially virologically suppressed population or patients.
There's a clear unmet need here since an estimated 10%-30% of hepatitis B patients do not reach their treatment goal after a year or more on a NUC therapy. This is a sizable group that has no approved alternative approaches today. We can address this with vebicorvir. The addition of a core inhibitor may make deeper suppression of the virus possible for a greater percentage of these partially virologically suppressed patients so they achieve that treatment goal of having unquantifiable HBV DNA. If successful in this setting, vebicorvir would represent the first new mechanism approved in hepatitis B for about 25 years, and it has the opportunity to make a unique contribution to the field and to the patients that would require it.
Our second population will likely be treatment-naive patients for these registrational programs, as even for this group, a core inhibitor plus NUC regimen leads to faster and deeper viral declines, and the literature suggests that over time, this will correlate with better clinical outcomes. For chronic suppressive therapy, we have already achieved agreement with the Chinese regulatory body on our phase III registrational studies, and we are continuing our discussions with the FDA. We have been working with our partner, BeiGene, to prepare to initiate the phase III registrational trials globally and in China during the first half of next year, 2021. Stay tuned, please, for more details on that phase III program between now and the early part of next year. We've made good progress on that behind the scenes.
The second strategy is to pursue finite therapy, initially with a dual combination of vebicorvir and a NUC. While this strategy hasn't achieved what we had hoped in the experiments I've just described to you today, we continue to execute on the third arm of our strategy by developing more potent next-generation core inhibitors, ABI-H2158 and ABI-H3733, which are structurally distinct from vebicorvir and from each other. In our clinical studies, ABI-H2158 demonstrated 10-fold greater potency than vebicorvir, and ABI-H3733 showed 40- to 50-fold greater potency than vebicorvir in inhibiting the formation of new cccDNA, which is crucial to depleting the mini chromosome pool. For ABI-H2158, we continue to enroll patients in a phase II multicenter randomized placebo-controlled trial in combination with entecavir in treatment-naive e-antigen-positive patients.
ABI-H2158 also has FDA Fast Track designation. We anticipate sharing interim phase II data in 2021, next year. In parallel, ABI-H3733 is in a phase I study evaluating the safety, tolerability, and pharmacokinetics in healthy subjects at the current time. The fourth and final strategy of what we've been trying to do over the last year or two is to study what can be achieved by introducing additional orthogonal mechanisms to the core inhibitor plus NUC regimen. Combining multi-drug regimens with non-overlapping mechanisms has the potential to generate higher response rates in certain populations of patients. During the first half of 2021, we plan to initiate a phase II trial that will evaluate vebicorvir combined with a NUC and Arbutus' RNAi therapeutic AB-729 as a treatment for patients with chronic hepatitis B.
We have also been planning in parallel to initiate a triple combination study in the first half of 2021 to evaluate the addition of interferon with its many pleiotropic immunomodulatory mechanisms of action to the vebicorvir and NUC dual combination regimen. We're well-positioned to move ahead with these three strategies in parallel because we have the right team to work on hepatitis B and move the field forward. I've said this repeatedly. I'm proud to be working with a team of veterans in liver disease and virology who have deep experience in hepatitis B. They span the research, clinical, operational, and regulatory functions, just to name a few, and have all worked tirelessly to advance new treatments for patients.
This is a team that can rise to the challenge, and we have the resources to support our efforts with cash that's expected to fund our planned activities into the second half of 2022. Before we open the call to Q&A, I'd like to summarize what's on the horizon for the company. Next week, we will have four posters at AASLD, including two late breakers. Among these are the phase II safety profile for vebicorvir, which continues to be differentiated, and more on the potency and resistance profile of ABI-H2158 and ABI-H3733 versus vebicorvir from Bill Delaney's group. During the first half of 2021, we also expect to initiate the planned phase III chronic suppressive trials in China with BeiGene, as I've outlined today.
We also plan to initiate two triple combination studies, one with vebicorvir, NUC, and Arbutus' RNAi therapeutic AB-729, and the other with vebicorvir, NUC, and interferon. In 2021, we anticipate sharing interim data from the ongoing phase II trial of ABI-H2158, as well as the phase II treatment intensification trial for vebicorvir plus NUC in patients with partial virologic suppression that I've described to you today. With that, we are now happy to take your questions, and as a reminder, I have Luisa, Bill, and Tom here with me. Operator, if you could go ahead and open the Q&A session, that'd be wonderful. Thank you.
Thank you. As a reminder, if you would like to ask a question, you may press star one on your telephone keypad, and to withdraw your question, press the pound key. We will pause for just a moment to compile the Q&A roster. Your first question comes from the line of Salim Syed. Your line is now open.
Great. Thanks so much for the color, John. A couple from me, if I can. From the press release, it looks like most of the patients had relapsed post-treatment around week four. I'm wondering, one is, do we know that these patients are being treated long enough? Is the stoppage criteria correct, or does it put the stoppage criteria that's been put in place into question? Also, along the same lines, does this put into question what we know about cccDNA turnover being into that 16 to 28 week timeframe, or is there any possibility here that it's actually longer than that?
The second question is, if you could just outline, because I think it'd be helpful for folks, the chronic suppressive therapy value proposition, both from a dollar perspective and also from a clinical perspective of what it actually means for patients, clinically and why it's meaningful, to be knocking down virus faster but still not being able to get to finite therapy, if they were to take a core inhibitor with a NUC. Thank you.
Thanks, Salim. Three questions. I'll start. I'll ask Bill Delaney to chime in a little bit on cccDNA, and then Tom and I will address the chronic suppressive therapy proposition. Have we treated the patients long enough with vebicorvir and a NUC 12 to 18 months, I said today? Are our stopping rules adequate? Is the turnover of cccDNA longer than we think it is, which is what you might have intimated, or is it actually just the potency of this drug in terms of a finite therapy? We know it's a potent drug. There are DNA and RNA reductions in a 24-week period of time, 48-week period of time that we see that's leading to our work on chronic suppressive therapy. I don't know all the answers to those questions right now.
I do feel, though, as I've said before, that this is a critically important mechanism of action. It blocks three additional steps in viral replication. If it is a potency issue, we have more potent compounds as I've described coming behind. Bill, why don't you have a word or not about what you think the result of this experiment means in terms of cccDNA half-life or durability or ability to eradicate? I don't think it does answer the question, but I'd like to hear what you said.
John, thanks. I agree with what you said. The figures that you cited, Salim, are the best figures that we have now, but they are estimates. You cited, Salim, are the best figures that we have now, but they are estimates, obviously, hard to directly measure given the location in the liver and the difficulty in getting biopsies. I think this could be related to potency in addition to potentially the half-life being longer, in particular the second activity of the compounds to block the formation of new cccDNA. That's a question we can answer with the compounds coming along in the pipeline following vebicorvir. That's something we had in mind from the beginning that we didn't know what level of potency we needed to reach.
Thank you, Bill. The other thing I would say, Salim, is that the result of this experiment doesn't make me feel any less enthusiastic about core inhibitors doing what they're doing because we know there's a greater reduction in DNA, there's a greater reduction in pgRNA over that period of time. I also still strongly believe that pgRNA reflects cccDNA. We've got some more data we're showing in some of our posters at AASLD and some more clinical data around that with one of our collaborators as well. This result shouldn't be misconstrued as pgRNA no longer being a good surrogate for cccDNA. I don't think there's anything that suggests that. Salim, the last question. We haven't answered your question, but we've said a lot, but we're talking to you here. We haven't got all of those answers right. Chronic suppressive therapy. I haven't talked about this.
I've mentioned it on and off. If you look at the literature, particularly in e-antigen positive patients that start higher baseline viral loads, 10%-30% of patients, it might be 10% for e-antigen negative and up to 30% for e-antigen positive, do not suppress, and they have residual detectable HBV DNA at the end of one year or 48 weeks of therapy. That is an unmet need. It's an unmet need for which there's no approved drugs. The regulators understand this, and it's a unique opportunity. That is something that we have felt very strongly, where there is a place for our drug right now, independent and in parallel of the experiment we were doing and described today, the stopping experiment. That's why we've been doing it.
It's why we found BeiGene as a partner, because we need to get this started, and our data set and our regulatory interactions support us getting started. Tom, I've talked about the importance from a clinical perspective, Salim, but Tom might want to talk about opportunity.
Sure, John. I can add just a couple of comments to that. Obviously, you talked about the unmet need, and you highlighted one group. When we're through our regulatory interactions, we can be more specific about the full design of the phase III program. A way you can think of this maybe in terms of the potential opportunity is that hepatitis B, as recently as 2017, before one of the products went generic, was a $3 billion global market. We're talking about an unmet need group that doesn't have an option today that we can uniquely address with vebicorvir that has a 10%-30% patient population readily identifiable. I think in terms of what the order of magnitude could be of the commercial opportunity, it can give you a flavor or a range, and we think that is meaningful for a company of our size.
Got it.
Thanks, Salim.
Thanks so much for the details, guys. Thank you.
Your next question comes from the line of Mr. Geoffrey Porges.
Great. Thank you very much. Obviously, we're going to follow up on this question, John. My first question is, if you're suppressing the HBV RNA to undetectable levels, then how could a second or third generation more potent antiviral suppress it even more? What in this data or in any other data set gives you confidence that just an increase in potency is going to make a difference? I thought the theory here was that a prolonged suppression would prevent the turnover of the HBV DNA and therefore lead to the gradual wind down of that residual HBV DNA. Why do we care about a more potent drug? Should we really just evaluate this on the potential for that small group of patients for whom suppressive therapy might be beneficial and justified?
Thanks, Geoff. I don't think we should evaluate the drug just on the potential for it to be a drug used for patients who've got partial virologic suppression as a better chronic suppressive therapy. I still believe that with a more potent drug that's acting on the target and acting on cccDNA more potently for 24 hours a day, we should be able to completely shut down, in some patients, cccDNA. That's the hope. We could achieve that with a more potent drug. We are using assays as well, Geoff, that are very sensitive, but it could be that there's some logs or some small amount of cccDNA not reflected in peripheral serum pgRNA that's persisting as well. Bill and I often talk about this as well.
I do believe that we need to do the experiments with the more potent drugs, looking at different sets of stopping criteria. Perhaps we can modify them and make them more stringent. I'm not sure we can come up with a more sensitive assay for pgRNA. We've really pushed the technology there. Then I would just ask Bill to talk something about the characteristics of drugs and their potency in terms of what they're doing in the hepatocytes and their on action on formation of cccDNA, et cetera.
Yeah. Thanks, John. I agree with what you've said. We know NUCs don't get rid of all the replicating DNA in the periphery. We know that the serum also only gives us a glimpse of what's going on in the liver, and we've pushed the assays to the limits we can. Maybe they could come a little further, but in terms of the potency of the drug, I think we need to turn off viral replication completely to be able to see the turnover consistently or to get the maximum slope on the turnover.
The compounds coming in the pipeline behind vebicorvir, one of the things we focused on was the second activity of not just blocking active replications, but preventing the formation of new cccDNA, and as we've said here, the newer compounds are in order of magnitude or more potent, 10 for ABI-H2157, ABI-H2158, and 40-50 fold more potent against that cccDNA formation activity for ABI-H3733.
Geoff,
I'm sorry.
Thank you, Bill. The other thing I would say, Geoff, is virology 101. If we are going to be able to create better curative or finite therapies for hepatitis B, it's got to be about non-overlapping orthogonal mechanisms of action. Core inhibitors are blocking three additional mechanisms of action within the viral life cycle. If we can apply potency to that, I believe, and I've always believed that we should be able to get there. Whether we need a dual combination for some patients, whether we need triples for other patients, we've got all of those experiments ongoing. They are our parallel strategies as well as our chronic suppressive therapy. Long answer. Can't answer it, but that's my thoughts on it, Geoff. I hope that's okay.
John, I just want to follow up on this because if I'm going to the bottom of the Grand Canyon and then I'm staying at the bottom of the Grand Canyon in terms of viral load, the Grand Canyon doesn't get any deeper in terms of it being undetectable, so do I really care about a more potent antiviral that takes me down the slope faster? That's where I think the analogy with HCV I'm struggling with, because of course, HCV, it was about shrinking the duration of treatment, whereas here, you had super prolonged suppression of detectable virus. Again, what's the evidence that it matters how potent it is other than HCV?
Well, I think it's the historical perspective about virology here, Geoff, that even when you get to something that you can't measure, you know you've got a number of logs below that.
You might think you're at the bottom of the Grand Canyon, but there's another part of the Grand Canyon that's a lot deeper somewhere else. I mean, that's the basis and the hypothesis of our driving viral replication down with the most potent drugs of each class. Bill, do you want to say something else or no?
Yeah, no, just in that analogy with the bottom of the Grand Canyon, there are several pieces of literature that suggest that there's more replication going on in the liver than you can see in the serum. We can't measure everything by the serum, although that's the practical thing we can measure during a clinical trial on a longitudinal basis.
Yeah, I would agree, we don't know that we're at the bottom of the Grand Canyon yet, and until we reach the bottom of the Grand Canyon, we won't accelerate that slope.
Okay. All right, thanks. Good luck.
Your next question comes from the line of Mr. Michael Yee. Your line is now open.
Hi, thank you. You have [Kaleh Shiyon] for Michael. I guess related to the prior question from Geoffrey Porges. In the data that you'll be collecting and analyzing, is there anything specifically that you'll be looking for to give you confidence that you're actually going down the right path with capsid inhibitors? Related to that, also, I know it's early, but can you speak to whether there were any meaningful differences in the viral set points for the various markers, specifically pgRNA, following a relapse? Thanks.
Yeah. We're still analyzing all of the viral set points, and this is a rolling data set. We've got new pieces of data almost every day this week, and this is a very recent change. I can tell you that it wasn't so many days ago where in the e-antigen negative set of patients, we were above my threshold or expectation for 15%. This is all happening real time, guys.
It's not something that we've been sitting on for a long period of time. I think we are trying to understand all of this. In terms of viral set points, I don't think we have any important information. I'll ask Luisa to comment on that. Your first question about are we heading down the right direction with core inhibitors. Core inhibitors are the only mechanism in patients with hepatitis B right now that have shown significant reductions in placebo-controlled trials compared to standard of care alone, that create greater reductions in DNA and pgRNA, and that's the premise for our package and our discussions with the regulators about better chronic suppressive therapies. There's nothing else out there that's really that far along. Viral set points, Luisa, do you want to say something about that?
I think it's very important that based upon this one experiment, which we were doing as a stopping therapy in parallel with the chronic suppressive therapy, in parallel with the more potent drugs, and in parallel with the triples, we don't just now discard the mechanisms. That is not the right approach, and it will not be our approach either. Luisa?
Yeah. Thank you, John. I think it's an excellent question. We're only beginning now the process of understanding these results. As John mentioned, it's really an emerging data set, and we're going to be learning as much as we can, which will inform our future studies and the field more broadly. I think thinking about the viral dynamics after cessation of treatment in the context of relapse will be very important. We'll be looking via more sensitive assays and other virologic biomarkers such as antigens. We are just beginning to get this data, and we're going to be looking at it very closely, and it's something that, in addition to the subgroup analysis that John was referring to in terms of understanding relapse and when they occurred in these subgroups, this is something, the viral dynamics and set point, as you say, we'll be investigating closely.
Reset point as well. One of the things is it delayed in some patients? It is. Are they different? Do they require retreatment? What happens to the viral load return, et cetera? Don't forget this is all ongoing right now. We haven't completed that. We've just started to look at this as well. As I said to you today, we'll be very keen to get this out at future meetings as well. It's important that we all see what the data looks like, so we'll work hard on doing that as soon as we can.
Got it. Thank you very much.
Thank you.
And your next question comes from the line of Mr. Brian Skorney, your line is now open .
Hey, good afternoon, guys. Thanks for taking my question. A couple of questions from me. I guess to start, John, you did a lot of work with VEMLIDY at Gilead, which seems to do pretty well, even with generic VIREAD out there, doing well in excess of $500 million in annual sales and still growing. I guess, can you help contextualize VEMLIDY's success in the face of sort of direct branded competition and how we should be thinking about the doublet therapy potential, the deeper suppression you get from it, versus that sort of market opportunity as a single agent branded product when you'd obviously be going to a doublet with a generic product?
Thank you, Brian. Appreciate you calling in late. Look, VEMLIDY was successful because it was differentiated. Bill actually did a lot of work on VEMLIDY as well, but it had a differentiation safety-wise, bone and kidney, that was very clear, and some other differentiators as well. It was a potent antiviral, it was low dose, cost of goods were very favorable as well. That helped VEMLIDY become successful, and really sort of replaced tenofovir in a lot of the markets as well. Why would a doublet be acceptable in that situation? Well, it would be differentiated. It would be differentiated in that it would be given to a group of patients who haven't suppressed after a year or more of VEMLIDY or tenofovir. They have 100 international units or 500 international units.
We add a core inhibitor, they stay on that combination, and then they suppress and get to their target of having unquantifiable HBV DNA. These are all the advantages, I think, of doing what we're trying to doing in the chronic suppressive therapy setting. Tom wants to say something as well.
Hey, Brian. I thought I would just add an additional perspective or two. I think it's very premature to talk about pricing strategy and reimbursement and things of that nature. I would just say that many of the products are already generic, and the one that you're talking about, not too far down the road will be, and so there's that consideration. Additionally, we're talking about, in particular here today, an unmet need group that we can identify and uniquely serve. I think when you go into a commercial situation, when you're in that position, that's the better place to be.
Right. Just on the SVR data, understood that just very early days and you don't have any sort of definitive measures to kind of look at what's going on underneath. Is there anything that you would speculate or hypothesis test in terms of the differential and the time course of relapse between the positives and the negatives? I mean, I realize it's small numbers, but it does look like there is sort of a separation there and any hypothesis in terms of what you think the sort of rapid relapse of the positives versus sort of what may be a slower relapse in the negatives implies?
Early days, Brian, but the observation's there, and it's an observation that others have made in e negative patients treated with standard of care or NUCs alone. We know that the half-life of the residual amount of cccDNA in e negative people is lower, and viral replication has different dynamics in e negative than e positive patients. How that contributes to the observation, we don't know the answer yet. We are working and have a continued relationship with some modelers as well. We will be looking at modeling this as well, seeing if it informs anything about rates of relapse in the two populations. I don't have the answer right now.
Okay. Thanks.
Your next question comes from the line of Nicole Germano. Your line is now open.
Hi. Good evening. Thanks for taking my question. Looking across the core inhibitors, vebicorvir looks like it has a better safety profile and based from the biology and what you know from this data set, going forward, what would be the best components to combine with vebicorvir? Would you want to combine with NUC and with your siRNA as an immune component and an immune booster? Or is one of these redundant, and would it make sense knowing the biology, and basically, would it make sense to add a fourth component?
Thank you, Nicole. It's John again. Vebicorvir will be, as I've explained today, in parallel, explored as a chronic suppressive therapy. That data set exists, the data supports that, and we're doing that. That's separate. You're asking a very good question. Should we do other experiments with a vebicorvir and a NUC with different stopping criteria, et cetera, or the third mechanism? We've said today, as I've said previously, we are looking at the third mechanism, which is the siRNA collaboration with Arbutus. We're also, as I've announced today, but I've sort of talked about also separately, we'll look at a triple combination with interferon. We're doing all of those. The quad we've discussed internally, and we'd like to understand the safety of the triple before we would consider some form of a quad experiment.
That seems very logical to do that. To get back to your first point, Nicole, we do understand the safety profile of the drug. We can do these experiments with other mechanisms, and we can tease out the individual contribution of a safety signal, et cetera. Because we do, as I've said before, and as you intimated today, we do have a drug in vebicorvir that has a differentiated safety profile compared to the other core inhibitors currently. We have a nice abstract at AASLD on the expanded data set coming up in a couple of weeks in terms of the safety profile of the drug as well. That's one of our abstracts at AASLD. Thanks for asking the question. It's a good question. Step by step, triples before anything else.
Great. Thank you.
Thank you.
Again, to ask a question, you may press star one on your telephone keypad. Okay, your last question comes from the line of Mr. Rahul Prasad. Your line is now open.
Thanks for taking the question. A couple for me. Just given what we're seeing here, just some thoughts on the dosing regimen for vebicorvir in some of these triple combo studies, particularly RNAi, or I say, RNA study. Do you think 12 weeks would be enough with vebicorvir? If it was a finite treatment, would you need to do chronic treatment with VBR? Just given what we know on Study 211, given what we know about the half-life of cccDNA and the amount of time it takes to deplete pgRNA, are you surprised at all about the four-week numbers and just how quickly relapse occurred? Thanks.
Thanks, Raj. In terms of the first question in the triples, I think you were intimating about the triples. Our plan is to use the same dose of vebicorvir, and to have the duration at least 24 weeks. If we start to change multiple different parameters or variables, we'll never be able to answer those questions. If we start longer duration, get a positive result, then we can try and chip away at duration and see if we lose any efficacy. We have to have that efficacy signal first. That will be the approach in terms of the triple combinations to answer that. Then the second question, would you like to answer that, Luisa or?
Raj, could you repeat your second question? I wasn't sure if you were talking about the duration of the combination treatment or the time point post-treatment, which is what.
Oh, the time of relapse. Sorry, the time of relapse. Sorry, Raj.
Yeah, post-treatment.
Yes. Yeah. Apologies. Yeah. It's been a long couple of days here getting ready for this call, as you can imagine. Look, the e-antigen, there's definitely a difference in the rapidity of relapse in the e pos versus the e negatives. That's not surprising to me, really, because of what I said before, that there's a lower viral burden and a lower copy number of cccDNA and a lower turnover and a different half-life of the virus in e-neg patients. I think that's what it's reflecting, and that's what my theory is or our theory is, and Bill's shaking his head here as well. We do have to do the modeling on the rate of return of the viruses, both DNA and RNA, and to see if our modeling fits that hypothesis. That's what we will have planned in the future when we have the complete data set.
Great. Thanks.
Thank you.
There are no further questions, and I will now turn the call back to Assembly Bio's CEO and President, Dr. John McHutchison, for closing remarks.
Thank you. In closing, I'd like to thank all of our dedicated employees at the company, and I'd also like to recognize the investigators involved in our trials, the patients participating in the studies, and the shareholders who support our efforts. You are all essential to the progress we are making towards improving and developing better therapies for patients with hepatitis B. I'm confident, as I said today, that we have the right team and the resources to push towards our goals for next year and beyond. Thank you again for joining the call today. I know it's late, and this concludes our call for the day.