Arbutus Biopharma (ABUS) Q4 2020 Earnings Call Transcript

Arbutus Biopharma (ABUS 1.47%)
Q4 2020 Earnings Call
Mar 04, 2021, 8:45 a.m. ET

Contents:

• Prepared Remarks
• Questions and Answers
• Call Participants

Prepared Remarks:

Operator

Ladies and gentlemen, thank you for standing by, and welcome to the Arbutus Biopharma Corporation fourth-quarter and year-end 2020 financial results and corporate update conference call. [Operator instructions] Please be advised that today's conference is being recorded. [Operator instructions] I would now like to hand the conference over to your speaker today, Pam Murphy. Thank you.

Please go ahead, ma'am.

Pam Murphy -- Investor Relations Consultant

Good morning, and thank you for joining the Arbutus Biopharma fourth-quarter 2020 conference call and webcast. On the call today are Bill Collier, president and chief executive officer; Dr. Gaston Picchio, chief development officer; Dr. Michael Sofia, chief scientific officer; and Dave Hastings, chief financial officer.

Bill will begin with a summary of recent accomplishments and upcoming events and a review of Arbutus' 2021 corporate objective, followed by Gaston, Mike Sofia, and Dave Hastings, who will provide clinical drug discovery and financial updates, respectively. Please note Gaston will be using a few clinical slides, which can be viewed on the webcast. After the speakers, we'll then open up the call for Q&A. Before we begin, we'd like to remind you that some of the statements made during the call today are forward-looking statements, including statements regarding expectations, timelines, and clinical results for Arbutus' proprietary HBV pipeline and COVID-19 preclinical research efforts, the company's 2021 objective and expected cash use and cash runway.

These forward-looking statements are subject to a number of risks and uncertainties that may cause our actual results to differ, including those described in our most recent annual report on 10-K, quarterly report on Form 10-Q, and other periodic reports filed with the SEC. I would now like to turn the call over to Bill. Bill?

Bill Collier -- President and Chief Executive Officer

Thank you, Pam, and good morning, everybody. Thank you for joining us today. As I approach my two-year anniversary with Arbutus, I'd like to use the next few minutes to summarize the progress that we have made and why I believe that Arbutus is well-positioned to execute on our mission to develop a cure for people with chronic hepatitis B, as well as advance new proprietary therapies to treat coronaviruses. First of all, and Gaston Picchio will describe in more detail, our lead product, AB-729, a subcutaneously delivered RNAi agent, has demonstrated the potential to be a cornerstone drug in future HBV combination regimens.

We've reported in 2020 a significant body of compelling safety and efficacy data from an ongoing Phase 1a/1b clinical trial. And this data strongly supports our plans to initiate two Phase 2 trials for 729 in combination with one or more approved or investigational agents in the second half of 2021. In addition, Arbutus and Assembly have initiated screening of our proof-of-concept Phase 2 clinical trial combining 729 with Assembly Biosciences capsid inhibitor, vebicorvir, and a nucleoside reverse transcriptase inhibitor. Secondly, we've completed the IND-, CTA-enabling studies for AB-836, our next-generation oral capsid inhibitor.

836 is from a novel chemical series, which we believe is differentiated from competitor compounds and offers the potential for increased efficacy and an enhanced resistance profile. We expect to begin the Phase 1a/1b clinical trial for 836 in the first half of 2021. Thirdly, as Mike Sofia will describe, we have a number of active drug discovery efforts in the HBV field, as well as discovery efforts for potential oral therapies to treat coronaviruses. Given our experienced chemistry and biology teams, and the investments we're making in the oral PD-L1 inhibitor and RNA destabilizer programs, we believe these programs have the potential to lead to future proprietary combination regimens to treat HBV.

Furthermore, we're confident that the proven expertise in virology that resides within our discovery team could lead to new oral therapies to treat coronaviruses. And finally, as Dave Hastings will describe in a moment, we have a solid financial position with a cash runway that now extends through the third quarter of 2022 and a demonstrated track record of efficiently raising capital. So with that, let me now turn the call over to Gaston Picchio, our chief development officer. Gaston?

Gaston Picchio -- Chief Development Officer

Thanks, Bill, and good morning, everyone. Today, I will focus my time on describing our current perspectives on AB-729 and our 2021 plans and objectives at as it relates to our lead clinical asset. As part of my discussion today, I will refer to a few slides that are available as part of our webcast and can also be found in our current corporate presentation located on the Arbutus website. First, let me reiterate Bill's confidence in the growing clinical data that has already emerged from our ongoing Phase 1a/1b clinical trial for AB-729.

Now, you can see in the first slide, the design of our Phase 1a/1b single- and multiple-dose clinical trial and the current status of the cohorts that have been completed and reported on, and these are in dark red and dark blue. Notably, this represents a significant data set and allow us to begin to put in perspective the potential of this drug, which I will address momentarily. We expect to report additional data from the ongoing cohorts from this trial in the first half of 2021, except for the 90-milligram every-12-week cohort, which is expected in the second half of 2021. In the next slide, No.

6, you can see that a single dose of AB-729 provided impressive and comparable mean S-antigen declines across all three doses, namely 60, 90, and 180 milligrams. Moving to Slide No. 7. Importantly, as demonstrated, repeat 60-milligram dosing of AB-729 every four weeks resulted in continuous mean S-antigen declines beyond week 12.

Now, as the next slide shows, repeat dosing using 60 milligrams every eight weeks resulted in comparable mean S-antigen declines relative to the 60-milligram dose every four weeks at week 16, or with minus 1.87 log10 versus minus 1.44 log10. Moving to the next slide, No. 9, you can see that in HBV DNA-positive chronic hepatitis subjects, a single 90-milligram AB-729 dose resulted in a robust mean S-antigen decline of minus 1.02 log10, similar to what has been seen in HBV DNA undetectable subjects. Notably, HBV DNA also declined at week 12 with a mean decline of minus 1.53 log10, as well as HBV RNA and core-related antigens, which are not shown here, supporting complete target engagement by AB-729.

Finally, Slide No. 10. AB-729 continues to be safe and well-tolerated. We have not seen any treatment-emerging grade 3 or 4 adverse events or discontinuations in any cohort to date.

In cohort F, two subjects had symptomatic ALT elevations; one subject with a history of grade 1 ALT elevation prior to trial entry had a transient grade 2 elevation, which evolved back to grade 1; while another subject had a transient grade 1 elevation. Further, in cohort E, the two subjects previously reported with grade 2 and two subjects with grade 1 ALT elevations have improved to grade 1 and grade 0, respectively, after week 24. All seven subjects in the cohort have consented to continue dosing with AB-729 for an additional six months. So stepping back with the totality of data we have seen thus far, we believe AB-729 can serve a vital role in our future proprietary combination regimens, both in lowering HBV replication and S-antigen concentrations.

Not only does AB-729 provide an efficacy and safety profile competitive with other programs, but it also potentially represents a competitive advantage in frequency of dosing. This gives me great confidence in our plans to aggressively advance AB-729 into several Phase 2 trials this year. We plan on initiating two Phase 2 combination trials with one or more approved or investigational agents in the second half of this year. In addition, we have initiated screening in our Phase 2 clinical trial combining AB-729 with Assembly Biosciences' lead core inhibitor, also known as capsid inhibitor, vebicorvir.

This proof-of-concept trial is a randomized, multicenter, open-label Phase 2 clinical trial that will explore the safety, pharmacokinetics, and antiviral activity of the triple combination of AB-729, vebicorvir, and an NrtI compared to the double combinations of vebicorvir with an NrtI and AB-729 and an NrtI.This trial is expected to enroll approximately 60 virologically suppressed patients with chronic HBV infection. So with that, I turn the call over to Mike. Mike?

Mike Sofia -- Chief Scientific Officer

Thanks, Gaston, and good morning, everybody. I want to briefly review our drug discovery objectives and strategies as we progress on the HBV and coronavirus research fronts. As you know, we are focused on developing proprietary combination regimens that have the power to functionally cure people with HBV. We have progressed compounds into development that target two critical pieces of our strategy: stopping viral replication and reduce S-antigen levels.

The other pillar of our strategy envisions addressing the immune component of the disease. To that end, we believe our oral PD-L1 program has the potential to reawaken the immune system in HBV patients. Highly functional HBV-specific T cells within our immune system are believed to be required for long-term HBV viral resolution. However, HBV-specific T cells become functionally defective and greatly reduced in their frequency during chronic HBV infection.

One approach to boost HBV-specific T cells is to target the PD-L1/PD-1 axis to release the brakes on the immune system and lead to removal of infected hepatocytes. We are in lead optimization with oral compounds, which are potentially capable of reawakening patients' HBV-specific immune response by inhibiting PD-L1 interactions. In addition, we believe that an all-oral proprietary combination of agents remains an objective for us. We continue to optimize HBV RNA destabilizers that are small-molecule, orally available agents that cause the destabilization and ultimate degradation of HBV RNAs.

Currently, we are advancing several promising next-generation oral HBV RNA destabilizers through lead optimization and candidate selection. Finally, we believe it is important to leverage our virology expertise in the battle against coronaviruses. Our effort is focused on the discovery and development of new molecular entities that address specific viral targets, including the nsp12 viral polymerase and the nsp5 viral protease. These targets are essential viral proteins, which have the potential for delivering pan coronavirus therapies, which Arbutus has experience in targeting.

As all of you know, predicting hard and fast timelines in drug discovery is not possible. Therefore, we are not yet giving specific guidance regarding when we will nominate lead candidates in these three areas. That said, we have a capable and experienced drug discovery team, and I look forward to updating you on our progress throughout the year. With that, I'll turn the call over to Dave.

Dave?

Dave Hastings -- Chief Financial Officer

Thanks, Mike. Good morning, everybody. Our ending cash, cash equivalents, and short-term investments was approximately $123 million as of December 31, 2020, compared to approximately $91 million as of December 31, 2019. Our cash used from operations for the year ended December 31, 2020, was approximately $51 million.

We made a $2.5 million equity investment in Genevant in July. These cash outflows were offset by approximately $86 million of net proceeds from the issuance of common shares under the Arbutus ATM program. Additionally, thus far, during the first quarter of 2021, we have received $24 million of net proceeds from our ATM program. We expect a net cash burn of between $70 million and $75 million in 2021.

And therefore, we believe our cash runway now extends through the third quarter of 2022. Finally, as a reminder, Arbutus owns approximately 16% of the common equity of Genevant Sciences, a company Arbutus launched with Roivant Sciences and to which Arbutus licensed exclusive rights to its LNP delivery technologies for RNA-based applications outside of HBV. We are entitled to receive tiered, low single-digit royalties on future sales of Genevant products covered by the licensed patents. If Genevant sublicenses the intellectual property, licensed by us to Genevant, we are entitled to receive upon the commercialization of a product developed by such sublicensee the lesser of 20% of the revenue received by Genevant for sublicensing and tiered, low single-digit royalties on product sales by the sublicensee.

So with that, Bill, I'll turn the call back to you.

Bill Collier -- President and Chief Executive Officer

All right. Thank you, Dave, and to Gaston and Mike. And I think at this point, operator, can you please open up the lines for questions and answers, please?

Questions & Answers:

Operator

[Operator instructions] And your first question Ed Arce with H. C. Wainwright.

Ed Arce -- H.C. Wainwright -- Analyst

Great. Good morning, and thanks for taking my questions. Congrats on a productive year. A couple questions from me.

You mentioned with 729, two trials that you're intending to start, I think you said in the second half of the year, sort of combination trials. I'm wondering if you could give us a little more detail on the intended design with those. In particular, have you chosen one or more doses, perhaps the 60- or 90-milligram? At least, in one of those committed to a dosing interval, I know that you're very interested in going with once every 12 weeks. And any other sort of details around the trial designs there would be helpful.

Thank you.

Bill Collier -- President and Chief Executive Officer

Thank you for the question, Ed. Just a couple of comments, and then I'll let Gaston answer with any additional detail. I mean, I think what we're trying to communicate today is our confidence in 729 going forward, where, in total, we will kick off three Phase 2 studies this year. The first one, obviously, being the Assembly study, which has initiated.

We did that press release last week. And then today, we're talking about an additional two Phase 2 combination studies. We've not released too much detail about those at this stage. But I think you can see that by kicking off three Phase 2 studies, we clearly feel very confident about 729 moving forward.

And with that, let me hand it over to Gaston.

Gaston Picchio -- Chief Development Officer

Yes. Thanks, Bill, and thanks, Ed, for the question. So as Bill explained, we haven't released the details at this point of what those two additional Phase 2 studies may look like. But obviously, we are exploring potential combinations with both investigational and other approved agents and, obviously, try to exceed the number of drugs there by two.

So we're looking at three or more drugs in those studies. In terms of the dosing schedule, as you may already know, we are confident enough, based on the data that we presented toward the end of last year to use the every-eight-weeks in the Phase 2 in collaboration with Assembly. So I'll just reiterate what was included, Ed, in the press release, announced recently by Assembly on the start of the screening of the study that the dosing of AB-729 would include 60-milligram dose every eight weeks. So we're waiting, obviously, for the results of the other cohorts, especially the every-12-weeks, to decide whether it may be also worth exploring a dosing frequency of every 12, but that data is pending.

Ed Arce -- H.C. Wainwright -- Analyst

Great. That's helpful. And then just one other question from me. Just to remind us, for this year, are you expecting to release any new data of results from any ongoing studies?

Bill Collier -- President and Chief Executive Officer

Yes. So this is Bill. And I will refer everyone to the last slide in our corporate deck, which was refreshed and updated, is on our website, went up this morning. There we list out what we expect to deliver this year.

So we're talking about additional data from the 60-milligram multi-dose cohorts every four and every eight weeks in the first half, additional data from the 90-milligram multi-dose eight-week cohort in the first half, the 90-milligram 12-week data in the second half. We also expect to have some 90-milligram multi-dose eight-week dosing interval in HBV DNA positive subjects in the first half. I've already mentioned the two Phase 2 clinical studies we hope to kick off in the second half. And then as we already mentioned on this call, we expect to kick off the 836 Phase 1a/1b clinical study in the first half of the year.

Ed Arce -- H.C. Wainwright -- Analyst

Great. Thank you, Bill. Sounds like you have your hands full this year with a lot of clinical activity.

Bill Collier -- President and Chief Executive Officer

We do.

Ed Arce -- H.C. Wainwright -- Analyst

Thanks. Thank you, guys, for the questions.

Bill Collier -- President and Chief Executive Officer

Right. Operator, do we have additional questions?

Operator

Your next question comes from Brian Skorney with Baird.

Brian Skorney -- Baird -- Analyst

Hey, good morning, everyone. Thank you for taking my questions. I guess more of a big-picture, long-term question on 729. I mean, we have a pretty good idea in terms of early data, the impact that RNAi interference targeting can have on some of the biomarkers.

But as you kind of think about long-term development plan, what sort of data would you be looking to achieve on a biomarker basis to challenge patients to complete antiviral therapy withdrawal? And I mean, what sort of stopping criteria do you think are reasonable to use?

Bill Collier -- President and Chief Executive Officer

Good question. Thank you very much. Maybe Mike and Gaston, Gaston first, perhaps, to answer that one. I mean, we're talking hypothetically here because we have no plans at the moment to get into this.

But Gaston?

Gaston Picchio -- Chief Development Officer

Yes. Thank you, Brian. In terms of -- let me just go to the -- summarize what we've seen with RNAi so far. So I think RNAi have been shown to, obviously, lower S-antigen also, HBV RNA core-related antigen, E-antigen.

And I think we probably have one of the most robust data showing that 729 can also reduce HBV DNA in a very robust and rapid way. So the big question, I mean, obviously, is going to be should we continue treating and wait until S-antigen becomes undetectable, or can we before stop -- consider stopping patients, or could we stop patients earlier and see whether the immune system has sufficiently reawakened to continue the job and clear all S-antigens and obviously infect hepatocytes and so forth? And that's a question obviously that I don't think anyone has answered so far. What is clear, based on the Assembly study, is that stopping patients with undetectable HBV RNA and HBV DNA, even with a more sensitive assay, was not sufficient to achieve functional cure, defined as loss of S-antigen six months after end of therapy. So they saw relapse very quickly.

So in that sense, obviously, that study did not include an RNAi agent. And lowering S-antigen may favorably impact the immune system in such a way that upon stopping therapy, things may look a little bit different. But really, this is all speculation because nobody has stopped all therapies in RNAi subjects and see after a long dosing period of at least a year, in combination with other agents and see what happens. So we may be in a position to do that later this year in some of our cohorts and see what the turnout is.

But I can't give you a definitive answer what's going to happen. But certainly, that's one of the most important questions in the field right now.

Brian Skorney -- Baird -- Analyst

Right. Thank you.

Bill Collier -- President and Chief Executive Officer

And, Gaston, do you want to just briefly mention because on our corporate deck on our slides, we do show how many subjects get below either 100 or 10 international units per ml for surface antigen. Do you just want to comment on those numbers?

Gaston Picchio -- Chief Development Officer

Yes. So, yes, that's a great point. As you know, in some countries in Asia, especially, there's a tendency for subjects who have been on NUC therapy for a number of years, either S-antigen drops below 100 to actually stop the NUC and follow them very closely. And in some occasions, the subjects who achieve less than 100, which is a threshold that's used, I would say, clinically, most frequently, they tend to seroconvert, so lose S-antigen and some of them even develop anti-S-antibodies, which is the definition of functional cure.

So in our studies, we have pretty much, so far, the vast majority, like six out of seven have reached less than 100 in cohort E and even a couple of them have reached less than 10. So the big question is: In the setting of one year of duration of therapy, is that going to be sufficient? So these are questions that obviously, we're trying to decide whether achieving S-antigen below those thresholds, which have shown in other instances to be clinically relevant, would they be equally relevant toward functional cure when using RNAi agents, in this case, AB-729. So this is still evolving. We're evolving our thinking and trying to decide what would be the best approach to stopping therapy in patients who have received at least one year of AB-729 combination with NUC.

But those are some encouraging pieces of information that a large proportion of these have already crossed that 100 IU per ml threshold.

Brian Skorney -- Baird -- Analyst

Great. Thank you.

Operator

Your next question comes from Mayank Mamtani with B. Riley.

Mayank Mamtani -- B. Riley FBR -- Analyst

Thanks, team, for taking my question, and congrats on the progress. So maybe on the same line of thinking on the triple therapy, just two things stood out to me that you are doing an open-label study, and also the number of subjects 60, just looking at other trials, look different. So I'm just curious how you think about data disclosures here. And again, the off-treatment cure rate that's specifically your program, but also, like as we look externally, there are different approaches, core/capsid inhibitor approach, there's the immunomodulator approach.

Can you comment like, just at a high level, what's your perspective on one versus the other, your confidence level, and just given like the challenging off-treatment cure rates we've seen so far?

Bill Collier -- President and Chief Executive Officer

Yes. Thank you for the question. I think you started just by making reference to the clinical collaboration with Assembly. And you correctly pointed out that that's a Phase 2 study with 60 virologically suppressed subjects with HPV.

And essentially, it's comparing the triple, 729 plus vebicorvir plus a NUC versus 729 plus a NUC versus vebicorvir plus a NUC. The only thing that we have communicated with our partners, Assembly, on that is that the study has started. That was the press release last week. We've not indicated when we will have data available from that study.

Although it is an open-label study. So we will be able to track progress as we go. As to the second part of your question, perhaps, Gaston, I can throw that to you.

Gaston Picchio -- Chief Development Officer

Yes. And so hi, Mayank. It's difficult to say because, to be absolutely honest, we're not sure what the details of other studies are. I mean, I can just reiterate what our study, in collaboration with Assembly, is going to be looking at.

So basically, we're looking at E-antigen negative subjects who are being suppressed for at least six months with NUC therapy, and they're going to be enrolling into -- sorry, randomized into three different arms. So obviously, there are two arms would function as controls, and there's a third arm, which is the exciting arm, which is the combination of the three agents. So as to exactly the differences with other studies that may be looking at similar but not identical approaches, I can't really comment because I don't know the details behind their models and what you can find in clinical trials or goals. So I think it's always important, I mean, at least based on my experience, that despite the fact that there is a reiteration of mechanisms of action.

I think at least I've learned over the years that it's always important to see what different assets within a class can provide. So I wouldn't discount the fact that we're testing three drugs that other companies may be testing as less exciting because I think we've seen some interesting data coming out of 729. And also, vebicorvir has been well established in further suppressing HBV DNA and pgRNA. So the combination of those three in the population that we selected may play out differently than in other regimens.

So I think we have to wait for the results, in short.

Mayank Mamtani -- B. Riley FBR -- Analyst

Understood. And then just two more quick follow-ups. PD-L1 oral inhibitor, any color you could provide on time to IND? And just a high level, why to scale out the use in cancer, for example, maybe by a partner if you don't want to do oncology?

Bill Collier -- President and Chief Executive Officer

Mike, do you want to take that one?

Mike Sofia -- Chief Scientific Officer

Yes. Yes. Hi, Mayank. So look, we've made great progress in that program, and I'm very excited and optimistic about achieving a clinical candidate nomination in the foreseeable future.

And as I said, from discovery, it's hard to give a specific timeline. We want to make sure we bring forward the very best compounds. So we're clearly doing all the relevant studies that need to be done. And those need to be done before, I think, we're comfortable saying we have the candidate that's going to go into the clinic and give any guidance there.

On the cancer issue, look, we're fully aware of the potential for an agent like a PD-L1 inhibitor in other therapeutic areas, specifically cancer. And I think we will look at all options on how to exploit these other areas in the future. But right now, we're really focused on hepatitis B applications for these PD-L1 inhibitors.

Mayank Mamtani -- B. Riley FBR -- Analyst

Great. Thank you for that color. And lastly, on the Genevant-Moderna litigation, can you just remind us what's the next step there on the appeal to PTAB decision that was in July last year? What should we watch out for next?

Bill Collier -- President and Chief Executive Officer

Yes. Let me tackle that one. And then, Dave, you can chime in with any additional color as well. But you're referring back to the patent case that was announced last year where there was a challenge against one of Arbutus patents and was found in our favor.

And I think as we described at the time and subsequently in our various listings, that patent is one of those that has been licensed out to Genevant, which Dave described in his comments this morning. So, unfortunately, it's really not possible for us at Arbutus to comment on what Genevant may or may not be doing. Suffice to say that as part of that license-out arrangement, we've got some very clear terms for any sublicensing that Genevant may do, which is what Dave summarized in his comments. So I think that's about all that we can say.

Dave, unless there's any other additional comments you can think of.

Dave Hastings -- Chief Financial Officer

No, I think you covered it, Bill. Thanks.

Bill Collier -- President and Chief Executive Officer

OK. Great.

Mayank Mamtani -- B. Riley FBR -- Analyst

Thank you.

Operator

Your next question comes from Kelechi Chikere with Jefferies.

Bill Collier -- President and Chief Executive Officer

Good morning.

Kelechi Chikere -- Jefferies -- Analyst

Good morning and thank you for taking my question. I guess in the set of two Phase 2 combo studies slated to start later this year, can I actually speculate on what are some of the investigational or approved agents you're thinking you could potentially cure with 729? I think we're all aware interferon maybe something. What are some of the other agents you're thinking of? Any color there would be great. Thank you.

Bill Collier -- President and Chief Executive Officer

Yes. Good question. I mean, I can say that we want these three studies to be somewhat different so that we're exploring different combinations going forward. I mean, clearly, we have not said today what those compounds are going to be or could be, we've just said either marketed or investigational.

And I think the best way to answer that is with reference to our overall hypothesis that we want to be able to suppress DNA, we want to be able to suppress surface antigen and we want to be able to boost the immune system. That's our model and our strategy here at Arbutus for the way we can try and construct a combination therapy to achieve this functional cure for hepatitis B. I think that's about all we can say at the moment. So, Gaston, anything you want to add?

Gaston Picchio -- Chief Development Officer

No. Thank you. I mean, I think as you pointed out, that's how much we can say. But again, just reiterate our thinking, which is the importance of, first, lowering S-antigen to give the immune system, using different approaches, as Bill outlined, to reawaken and continue the job of clearing the effect of hepatocytes.

But we really believe that that lowering of S-antigen is critical to achieve that goal of functional cure and then intervene with other modalities after that is achieved. So keeping that in mind, I think you can imagine the different modalities that we're considering.

Kelechi Chikere -- Jefferies -- Analyst

Got it. That's helpful. Thank you.

Operator

Your next question comes from Roy Buchanan with JMP Securities.

Roy Buchanan -- JMP Securities -- Analyst

Hi. Thanks for taking the question. Just a quick one. Sorry if I missed this.

Any additional details on the RNA destabilizing you can provide? I mean, are you targeting the HBV RNA itself? Are you targeting a host protein? Any additional details? Thanks.

Bill Collier -- President and Chief Executive Officer

Mike?

Mike Sofia -- Chief Scientific Officer

HI. Mike Sofia. Hi, Roy. So we've actually described pretty extensively some of the mechanistic features of how the molecules that we are working with work.

Look, they do specifically target HBV RNA, and they target it via a mechanism that engages a host protein that's critical for stabilizing the HBV RNA poly (A) tail. And so by inhibiting that host protein interaction with a complex associated with HBV RNA, the PRE region of HBV RNA, we're able to destabilize HBV RNA and lead to the degradation of poly (A) tail or truncating of the poly (A) tail that ultimately leads to degradation of HBV RNA. So it is an HBV RNA-targeting modality, but it goes via a host protein that's critical for maintaining the stability of HBV RNA.

Roy Buchanan -- JMP Securities -- Analyst

OK, great. Thank you.

Operator

Our next question comes from Keay Nakae with Chardan.

Keay Nakae -- Chardan -- Analyst

Yes, thanks. So with the upcoming data, from the 60-milligram multi-dose at eight-week intervals and the 90 at eight- and 12-week interval, can you just tee up for us how many doses you expect to report on in each of those cohorts?

Bill Collier -- President and Chief Executive Officer

Yes. Gaston, maybe you can take that one. I don't want to be vague in the sense that we haven't released that in our guidance. But some of those cohorts have been ongoing for quite some time.

I think we just need to make sure that we have an effective and a realistic time frame to comment on. And by that, all I mean is that if you give something monthly, then within six months, you've got six doses. But if you could give something every 12 weeks within that same time frame, you've got many fewer doses. So we just want to make sure that we've got an appropriate number of doses to comment on.

Keay Nakae -- Chardan -- Analyst

OK.

Bill Collier -- President and Chief Executive Officer

But, Gaston, anything else you want to add?

Gaston Picchio -- Chief Development Officer

Well, I mean, let me just, I mean, articulate the question again. I mean, how many doses we're planning to report for both the 60-milligram every four and 60-milligram every eight weeks. As we pointed out in our guidance, so I mean, without counting the doses, I mean, the goal will be to be able to report end of therapy for both. So 48 weeks of treatment.

Keay Nakae -- Chardan -- Analyst

OK. Yes, that's helpful because, at some point, you're making the decision of when the math is enough and you're reporting it. So that's simply what we're looking for. It's really how far out do you want to go before you report.

Gaston Picchio -- Chief Development Officer

That would be the goal: to report end of therapy. And then obviously, pending decision around, as we were discussing earlier, and decisions around who can and who cannot stop later on, report on basically what happens off therapy in those that may qualify to stop. And that will be the structure, let's say, of every cohort that we're doing right now in the Phase 1a/1b study. So just to reiterate that.

The study was originally meant to have six months of duration in terms of dosing, with different doses and dose frequencies. The study was amended in such a way that patients on reaching the end of the six months can reconsent if they decide and the investigator decides, toward continuation for an additional six months, so that makes it basically a total of 48 weeks. And then after that, a decision will have to be made regarding stopping, either stopping completely all therapy or stopping just 729 and remaining on the NUC. So as all of these cohorts mature and they progress, specifically to your question, for cohorts E and F being the 60 every four and 60 every eight, the next goal will be to be able to report end of therapy.

Keay Nakae -- Chardan -- Analyst

OK.

Gaston Picchio -- Chief Development Officer

Is that helpful?

Keay Nakae -- Chardan -- Analyst

Yes, because you had pushed out the expected reporting of the 90 at 12 weeks. So just trying to understand what's behind that thinking.

Bill Collier -- President and Chief Executive Officer

Yes. OK. There's not so much. So I think we pushed that out.

That was one of the later cohorts to start. So it's just taken longer to go through, OK?

Keay Nakae -- Chardan -- Analyst

OK. Thanks.

Operator

I'm showing no further questions at this time. I would now like to turn the conference back to Bill Collier.

Bill Collier -- President and Chief Executive Officer

Thank you very much, and thank you all for your questions. Just to close out, I'll quickly review, once again, the key objectives for the company for 2021. So as you've heard on this call, we've already initiated the Phase 2 combination clinical trial to evaluate 729 in combination with the Assembly Biosciences core or capsid inhibitor, vebicorvir, and a nucleoside reverse transcriptase inhibitor. Secondly, we also expect to provide additional data from ongoing cohorts of the Phase 1a/1b clinical trial of 729 in the first half of 2021.

And as we also just mentioned, the 90-milligram every-12-week cohort will actually be expected in the second half of this year. We're also excited and expect to initiate two Phase 2 combination clinical trials in HBV subjects, including 729 with one or more approved or investigational agents. Again, that's slated for the second half of 2021. And we also expect to initiate a Phase 1a/1b clinical trial of 836, our next-generation capsid inhibitor, in the first half of 2021.

So I'd like to close out by thanking all of the staff at Arbutus. But importantly, this morning, all of you for joining us today, and we look forward to sharing our progress throughout the coming year. So thank you very much, and operator, that concludes our call.

Operator

[Operator signoff]

Duration: 50 minutes

Call participants:

Pam Murphy -- Investor Relations Consultant

Bill Collier -- President and Chief Executive Officer

Gaston Picchio -- Chief Development Officer

Mike Sofia -- Chief Scientific Officer

Dave Hastings -- Chief Financial Officer

Ed Arce -- H.C. Wainwright -- Analyst

Brian Skorney -- Baird -- Analyst

Mayank Mamtani -- B. Riley FBR -- Analyst

Kelechi Chikere -- Jefferies -- Analyst

Roy Buchanan -- JMP Securities -- Analyst

Keay Nakae -- Chardan -- Analyst

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