Good afternoon, and welcome to Assembly Bio's Phase 2 Extension 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 2 extension study, monitoring patients with chronic hepatitis B virus for sustained biologic response or SVR following discontinuation of treatment with bevacorvir 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 Q3 ended September 30, 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, Doctor.
John McCutcheson to provide opening remarks and then we will host a Q and A session. Joining John for the Q and A portion of the call will be our Chief Medical Officer, Doctor. Louisa Stan our Chief Scientific Officer of Virology, Doctor. 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, Doctor.
John McCutcheson.
Thanks, Lauren, and thanks to everyone for joining us today on short notice as well. While we are beginning to analyze the latest Study 211 data, 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 we'll continue to collect and analyze data with the goal of informing our development programs in the hepatitis B field generally. So 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 4 16 week time points following treatment discontinuation. The study is the 1st 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 12 to 18 months of treatment with our core inhibitor, vevicorVia and a nucleoside analog or Nuc. The patients who met the treatment stopping criteria was 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 CoBass assay with a low limit of quantified quantification of 20 international units for an SVR4 rate of 4% at the last visit. 16 of these patients first relapsed at post treatment week 4, but 6 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 4 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. But 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 and 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 of full viral suppression for the estimated 10% to 30% of patients who don't achieve that on a new colon, and we'll talk about this in a little while. And then eventually, of course, to the ultimate goal of finite therapies and then the cure or 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 2 studies we ran for hepatitis C, combining 3 distinct oral antivirals with interferon. While the results of this approach were disappointing in terms of the SVR rate and also The study provided important information, although studies provided important information that helped us push on. Ultimately, we learned from that and remains 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 analysis we will 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 of 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 1 here really, and the progress will be incremental. But 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 believe were the waves of development that the company would frame our approach to hepatitis B upon and that included 4 distinct and parallel strategies to advance our pipeline of core inhibitors. Even with today's setback, 3 of those 4 strategies remain on track. Unfortunately, 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 2 trial study 201 and 202 that the addition of VebicorVia to Nuc therapy can achieve a more rapid and complete level of viral suppression than same with Nucs alone and with the similar safety and tolerability profile.
These data form the basis for our intended Phase 3 registrational program for VEVCORVIA plus and NUC as better chronic suppressive therapy. We plan to include multiple patient populations in the Phase 3 registrational program and for it to be conducted globally and in China with our partner Beijing. 1 of the 2 populations we plan to include is the partially virologically suppressed population or patients. There's a clear unmet need here since an estimated 10% to 30% of hepatitis B patients do not reach their treatment goal after a year or more on a nuke therapy. And this is a sizable group that has no approved alternative approaches today, but we can address this with vevicorvio.
The addition of a core inhibitor may make deeper suppression of 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, 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 nuke regimen leads to faster and deeper viral decline. And the literature suggests that over time, this will correlate with better clinical outcomes.
So for chronic suppressive therapy, we have already achieved agreement with the Chinese regulatory body on our Phase 3 registrational studies and we are continuing our discussions with the FDA. We have been working with our partner Beijing to prepare to initiate the Phase 3 registrational trials globally and in China during the first half of next year, twenty twenty one. Stay tuned please for more details on that Phase 3 program between now and the early part of next year. So we've made good progress on that behind the scenes. The second strategy is to pursue finite therapy initially VEVICOR, VIA and Nuc.
While the strategy hasn't achieved what we had hoped in the experiments I've just described to you today, we continue to execute on the 3rd arm of our strategy by developing more potent next generation core inhibitors 2,158 and 3,733, which are structurally distinct from vevicorvir and from each other. In our clinical studies, 2,158 demonstrated 10 fold greater potency than vevicorvira and 3,733 showed 40 to 50 fold greater potency than bevicorvira in inhibiting the formation of new cccDNA, which is crucial to depleting the mini chromosome pool. For 2,158, we continue to enroll patients in a Phase 2 multicenter randomized placebo controlled trial in combination with entecover in treatment naive E antigen positive patients. 2,158 also has FDA fast track designation and we anticipate sharing interim Phase 2 data in 2021 next year. In parallel, 3,000 733 is in a Phase 1 study evaluating the safety, tolerability and pharmacokinetics in healthy subjects at the current time.
Now the 4th and final strategy of what we've been trying to do over the last year or 2 is to study what can be achieved by introducing additional orthogonal mechanisms to the core inhibitor plus new 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 twenty twenty one, we plan to initiate a Phase 2 trial that will evaluate Corvii combined with a Nuc and our butas RNAi therapeutic AB-seven twenty nine 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 twenty twenty one to evaluate the addition of interferon with its many pleiotropic immunomodulatory mechanisms of action to the vevicorovir and nuke fuel combination regimen. So 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 twenty twenty two. So before we open the call to Q and A, I'd like to summarize what's on the horizon for the company.
Next week, we will have 4 posters at AASLD, including 2 late breakers. Among these are the Phase 2 safety profile for Vebicorvira, which continues to be differentiated and more on the potency and resistance profile of 2,158 and 3,733 versus VebicorVia from Bill Delaney's group. We also plan to initiate 2 triple combination studies, 1 with Vevicor V and Nucan, our business's RNA therapeutic AB-seven twenty nine and the other with Vebicorv and NUCIN interferon. Also in 2021, we anticipate sharing interim data from the ongoing Phase 2 trial of 2,158 as well as the Phase 2 treatment intensification trial for Vebicorvior 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 Louisa, Bill and Tom here with me. So operator, if you could go ahead and open the Q and A session, that would be wonderful. Thank you.
Thank you. 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 for me, if I can. So from the press release, it looks like most of the patients had relapsed post treatment around week 4. So I'm wondering, one is, do we know that these patients are being treated long enough, I.
E. The stoppage criteria correct or does it put the stoppage criteria that's been put in place into question? And also along the same lines, does this put into question what we know about CCC DNA turnover being into that 16 to 28 week timeframe? Or is there any possibility here that it's actually longer than that? And then the second question is if you could just outline, I think it would 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 ANUCC?
Thank you.
Thanks, Salim. Three questions. I'll start. I'll ask Bill Delaney to chime in a little bit on ccc DNA and then Tom and I will address the chronic suppressive therapy proposition. So, yes, have we treated the patients long enough with Vebicorvira in a new 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.
So 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 3 additional steps in viral replication. And if it is a potency issue, we have more potence as I've described more potent compounds as I've described coming behind. Bill, why don't you have a word or not about what you think this 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.
Yes, John, thanks. And I agree with what you said. And the figures that you cited, Selim, are the best figures that we have now, but they are estimates. You cited Salim, they are the best figures that we have now, but they are estimates, obviously direct hard to directly measure given the location in the liver and the difficulty in getting biopsies. But I think this could be related to potency, in addition to potentially the half life being longer could be related to potency, in particular the second activity of the compounds to block the formation of new cccDNA.
So that's a question we can answer with the compounds coming along in the pipeline
Thank you, Bill. The other thing I would say, Salim, is that this doesn't 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 PG RNA over that period of time. I also still strongly believe that pgRNA reflects cccDNA. We've got some more data we're showing some of our posters at AASLD and some more clinical data around that with one of our collaborators as well. So this result shouldn't be misconstrued as pgRNA no longer being a good surrogate for CCCDNI.
I don't think there's anything that suggests that. Selene, the last question. So we haven't answered your question, but we've said a lot, but we're just we're talking to you here. We haven't put all of those answers right. Chronic suppressive therapy, I haven't talked about this.
I've mentioned it on and off. But if you look at the literature, particularly in the antigen positive patients that start higher baseline viral loads, 10% to 30% of patients 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 a year or 48 weeks of therapy. That is an unmet need. It's an unmet need for which there is no approved drugs. The regulators understand this and it's a unique opportunity.
And 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. So that's why we've been doing it. It's why we found Beijing as a partner because we need to get this started and our data set and our regulatory interactions support us getting started. Tom, any comments on 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 3 program. But 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 $3,000,000,000 global market.
And we're talking about an unmet need group that doesn't have an option today that we can uniquely address with vevicorviere that has a 10% to 30% patient population readily identifiable. And so 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 so much. Thanks so
much for the details guys. Thank you.
And your next question comes from the line of Mr. Geoffrey Porges. Your line is now open.
Great. Thank you very much. So obviously, we're going to follow-up on this question, John. So 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? And 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?
Because I thought the theory here was that prolonged suppression would prevent the turnover of the HBV DNA and therefore lead to the gradual wind down of that residual HBV DNA. So why do we care about a more potent drug? Or 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, Jeff. I don't think we should evaluate the drug just on the potential for it to be a drug used for patients who 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 CCC DNA that's the hope and we could achieve that with a more potent drug. We are using assays as well, Jeff, 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. And Bill and I often talk about this as well.
So 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. And 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 own action on formation of
cccDNA, etcetera. Yes. Thanks, John. And I agree with what you've said. We know nukes don't get rid of all the replicating DNA in the periphery, but we know that the serum also only gives us kind of 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 active replication, but preventing the formation of new cccDNA. And as we've said here, the newer compounds are an order of magnitude or more potent 10 for 2,157 2,158 and 40 to 50 fold more potent against that cccDNA formation activity for 3,733.
Jeff, the other thing I would say, Jeff, 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 and core inhibitors blocking 3 additional mechanisms of action within the viral life cycle. So if we can apply potency to that, I believe and have always believed that we should be able to get there. Now 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, Jeff. I hope that's okay.
But John, could I just 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 because and 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. So again, what's the evidence that it matters how potent it is other than HCV?
Well, I think it's just it's the historical perspective about virology here, Jeff, that even when you get to something that you can't measure, you know you've got a number of logs below that. So 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. And I mean, that's the basis and the hypothesis about driving viral replication down with the most potent drugs of each class. Bill, do you want to say something else or no?
Yes. No, just in that analogy with the bottom of the Grand Canyon, I mean, 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. So it's not we can't measure everything by the serum, although that's the practical thing we can measure during the clinical trial on a longitudinal basis. But yes, I would agree. We don't know that we're at the bottom of the Grand Canyon net.
And until we reach the bottom of the Grand Canyon, we won't accelerate that slope.
And your next question comes from the line of Mr. Michael Yee. Your line is now open.
Hi, thank you. You have Colette Scholesky on for Michael. I guess related to prior questions from Jeff or Gorges, in the data that you'll be collecting and analyzing, is there anything specifically that you'll be looking forward to give you confidence that you're actually going down the right path with CAT scan inhibitors? And 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, PGR RNA following a relapse? Thanks.
Yes. So, 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%.
So this is all happening real time, guys. It's not something that we've been sitting on for a long period of time. So I think we are trying to understand all of this. In terms of viral set point, I don't think we have any important information. I'll ask Louisa to comment on that.
And your first question about are we heading down the right direction with core inhibitors? I mean, 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, Louisa, do you want to say something about that?
So 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 mechanism. That is not the right approach and it will not be out of our approach either. Louisa?
Yes. 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 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 by our more sensitive assays and other neurologic biomarkers such as antigen. And 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 relapsed and when they occurred in these subgroups, this is something, the viral dynamics and set points, as you say, we'll be investigating closely.
And reset point as well. One of the things is, is it delayed in some patients? It is. Are they different? Do they require retreatment?
What happens to the viral load return, etcetera? So all of the don't forget, this is all ongoing right now. So we haven't completed that. We've just started to look at this as well. And we will 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. Yes. So thank you very much.
And your next question comes from the line of Mr. Brian Skorney. Your line is now open.
Hey, good afternoon guys. Thanks for taking the question. A couple of questions for me. I guess to start John, you did a lot of work with Vamiliti at Gilead, which seems to do pretty well, even with generic Viread out there doing well in excess of $500,000,000 in annual sales and still growing. I guess, can you kind of help contextualize Vamiliti's success in the face of sort of direct branded competition and how we should kind of be thinking about the doublet therapy potential, the deeper suppression you get from it sort of 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?
Yes. Well, I think the thank you, Brian. Appreciate you calling in late. Look, Vambletti was successful because it was differentiated. And Bill actually did a lot of work on VEMLIBI as well, but it had a differentiation safety wise, bone and kidney, that was very clear and some other differentiators as well.
And it was a potent antiviral with low dose cost of goods were very favorable as well. So 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 had a core inhibitor. They stay on that combination and then they suppress and get to their target of having unquantifiable HBV DNA. So 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 2. 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. And additionally, we're talking about, in particular here today, an unmet need group that we can identify and uniquely serve.
And I think when you go into a commercial situation, when you're in that position, that's the better place to be.
Great. And then just on the SCR 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. But is there anything that you would speculate or hypothesis test in terms of the differential on the time course of relapse between the positives and the negatives? I mean, I realize it's small numbers, but those 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 maybe a slower relapse in the negatives implies?
Early days, Brian, but the observation is there and it's an observation that others have made in a negative patients treated with standard of care or nucilone. We know that the half life of the residual amount of CCC DNA in E negative people is lower and viral replication has different dynamics in E negative and E positive patients. So 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.
So we will be looking at modeling this as well, seeing if it informs anything about rates of relapse in the 2 populations. I don't have the answer right now.
Okay. Thanks.
Your next question comes from the line of Ms. Nicole Herrino. Your line is now open.
Hi, good evening. Thanks for taking my question. So looking across the core inhibitors, bebicorrevir 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 Vebb Corvir? Would you want to combine with your siRNA as antigen component and an immune booster or is one of these redundant and would it make sense knowing the biology basically would it make sense to add a 4th component?
Thank you, Nicole. It's John again. So vevicorvira will be as I've explained today in parallel explored as a chronic suppressive therapy. So that data set exists, the data supports that and we're doing that and that's separate. But then you're asking a very good question.
Should we do other experiments with a Vebicorvira and nuke with different stopping criteria, etcetera, or the 3rd mechanism. And we've said today, as I've said previously, we are looking at the 3rd mechanism, which is the siRNA collaboration with our booties. And then 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. So we're doing all of those. Now 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.
And that seems very logical to do that. But to get back to your first point, Nicole, we do understand the safety profile of the drug. So we can do these experiments in with other mechanisms and we can tease out the individual contribution of a safety signal etcetera. So because we do, as I've said the other core inhibitors currently. We have a nice abstracted AASLD on the expanded data set coming up a couple of weeks in terms of the safety profile of the drug as well.
So that's one of our abstracts at AASLD. So thanks for asking the question. It's a good question, step by step triples before anything else.
Great. Thank you.
Thank you.
Okay. So your last question comes from the line of Mr. Rahul Prasad. Your line is now open.
Thanks for taking the question. Couple for me. One, just given what we're seeing here, just some thoughts on the dosing regimen for vevicorvir in some of these triple combo studies, particularly RNAi or RNA study. Do you think 12 weeks would be enough with evicorvir? If it was a finite treatment, would you need to do chronic treatment with VBR?
And then just given what we know on 211, given what we know about the half life of cccDNA and the amount of time it takes to deplete on pgRNA, are you surprised at all about the 4 week numbers and just how quickly relapse occurred? Thanks.
Thanks, Raj. So in terms of the first question in the triples, I think you were intimating about the triples. Our plan is to
24 weeks. We're not if
we start to change multiple different parameters or variables, we'll never be able to answer those questions. So 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. But we have to have that efficacy signal first. So that will be the approach in terms of the triple combinations to answer that. And then the second question, would you like to answer that Louisa 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 Sorry, the time of relapse. Sorry, Ryan.
Yes, post treatment.
Yes, apologies. Yes, it's been a long couple of days here getting ready for this call. So as you can imagine, so look, the E antigen, there's definitely a difference in the rapidity of relapse in the epos 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 eNEG patients. So I think that's what it's reflecting.
And that's what my theory is or our theory is, and Bill shaking his head here as well. But 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. So that's what we will have planned in the future when we have the complete data set.
Great, thanks.
Thank you.
So there are no further questions. And I will now turn the call back to Assembly Bio's CEO and President, Doctor. Jen Mark Hutchison for closing remarks.
Thank you. And 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. And thank you again for joining the call today.
I know it's late and this concludes our call for the day.