Arbutus Biopharma Corporation

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. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during this session, you will need to press star 1 on your telephone. Please be advised that today's conference is being recorded. If you require any further assistance, please press star zero. I would now like to hand the conference over to your speaker today, Pam Murphy. Thank you. Please go ahead, madam.

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 Piccio, Chief Development Officer, Dr. Michael Sophia, 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 objectives, followed by Gaston, Mike Sophia, 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's proprietary HBV pipeline and COVID-19 preclinical research efforts. The company's 2021 objectives is an expected cash use and cash runway. These forward-looking statements are subject to a number of risks and uncertainties that may cause their 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?

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 as Gaston Picquier will describe in more detail, Our lead product, AB729, a subcutaneously delivered RNAi agent, has demonstrated the potential to be a cornerstone drug in future HPV combination regimens. We've reported in 2020 a significant body of compelling safety and efficacy data from an ongoing phase 1a, 1b clinical trials. And this data strongly supports our plans to initiate two phase two 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 two clinical trial combining 729 with Assembly Bioscience's capsid inhibitor, vebicorvir, and a nucleoside reverse transcriptase inhibitor. Secondly, we've completed the IND CTA enabling studies for AB836, 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 Sophia 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 HPV. 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.

Thanks, Bill, and good morning, everyone. Today, I will focus my time on describing our current perspectives on AB 709 and our 2021 plans and objectives 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 RB2's website. First, let me reiterate Bill's confidence in the growing clinical data that has already emerged from our ongoing Phase IA1B clinical trial for AD729. Now you can see in the first slide the design of our Phase IA1B 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, number six, you can see that a single dose of AB729 provided impressive and comparable mean S antigen declines at width 12 across all three doses, namely 60, 90, and 180 milligrams. Moving to slide number seven, importantly, as demonstrated, repeat 60 milligram dosing of AB729 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 1.37 log 10 versus minus 1.44 log 10. Moving to the next slide, number nine, you can see that in HPV DNA positive chronic hepatitis subjects, a single 90 milligram AB729 dose resulted in a robust mean S antigen decline of minus 1.02 log 10, similar to what has been seen in HPV DNA undetectable subjects. Notably, HPV DNA also declined at WIC-12 with a mean decline of minus 1.53 log 10, as well as HPV RNA and correlated antigen, which are not shown here, supporting complete target engagement by AB 7 to 9. Finally, slide number 10, AB 7 to 9 continues to be safe and well-tolerated. we have not seen any treatment emerge in grade three or four adverse events or discontinuations in any cohorts to date. In cohort F, two subjects had asymptomatic ALT elevations. One subject with a history of grade one ALT elevations prior to trial entry had a transient grade two elevation, which evolved back to grade one, while another subject had a transient grade one 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 WID 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 AB729 can serve a vital role in our future proprietary combination regimens, both in lowering HPV replication and S-antigen concentrations. Not only does AB729 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 AB729 into several Phase II trials this year. We plan on initiating two Phase II 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 II clinical trial combining AB729 with Assemblies Bioscientist's lead core inhibitor, also known as Capsid inhibitor, the Vicorvirus. This group of concept trials is a randomized, multicenter, open-label phase 2 clinical trial that will explore the safety, pharmacokinetics, and antiviral activity of the triple combination of AD729, the Vicorvir, and an NRTI, compared to the double combinations of the Vicorvir with an NRTI and AD729 with an RTI. This trial is expected to enroll approximately 60 virologically suppressed patients with chronic HPV infection. So with that, I turn the call over to Mike. Mike?

Thanks, Gaston, and good morning, everybody. I want to briefly review our drug discovery objectives and strategies as we progress on the HPV and coronavirus research front. As you know, we are focused on developing proprietary combination regimens that have the power to functionally cure people with HPV. 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 infections. One approach to boost HPV-specific T cells is to target the PD-L1, PD-1 axis to release the breaks in the immune system and lead to removal of infected hepatocytes. We are in lead optimization with oral compounds, which are potentially capable of reawaking patients' HPV-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 essentially or essential viral proteins which have the potential for delivering pan-coronavirus therapies in 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?

Thanks, Mike. Good morning, everybody. Our ending cash, cash equivalents, and short-term investments was approximately $123 million as of December 31st, 2020, compared to approximately $91 million as of December 31st, 2019. Our cash use from operations for the year ended December 31, 2020 was approximately $51 million. We made a $2.5 million equity investment in January and 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 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 percent of the common equity of GenEvans Sciences. a company Arbutus launched with Royvant Sciences, and to which Arbutus has exclusive rights to its LNP delivery technologies for RNA-based applications outside of HPV. We are entitled to receive tiered, low single-digit royalties on future sales of GenEvant products covered by the license patents. If GenEvant sub-licenses the intellectual property licensed by us to GenEvant, we are entitled to receive upon the commercialization of a product developed by such sub-licensee a lesser of 20% of the revenue received by GenAdvance for such sub-licensing and tiered low-centre royalties on product sales by the sub-licensee. So with that, Bill, I'll turn the call back to you.

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?

As a reminder, if you would like to ask a question, please press star 1 on your telephone. To withdraw your question, press the pound or hash key. And your first question comes from Ed Arce with HC Rainwater.

Great. Good morning, and thanks for taking my questions. Congrats on a productive year. A couple questions for 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 doses? Have you, 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.

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 two 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 two 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 two studies, we clearly feel very confident about 729 moving forward. And with that, let me hand it over to Gaston.

Yeah, thanks, Bill, and thanks for the question. As Bill explained, we haven't released the details at this point of what those two additional phase two studies may look like. But obviously, we are exploring potential combinations with both investigation and other approved agents and obviously try to exceed the number of drugs there by two. So we were 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 towards the end of last year, to use the every eight weeks in the phase two in collaboration with assembly. So I'll just reiterate what was included in the press release announced recently by assembly on the start of the screening of the study, that the dosing of the AB729 would include the 60 milligram dose 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 dose and frequency of every 12. But that data is pending.

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

Yes, so this is Bill, and I will refer everyone to the last slide in our corporate deck, which was refreshed and updated. It is on our website. It went up this morning. But 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 HPV DNA positive subjects in the first half. I've already mentioned the two phase two 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.

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

Great.

Operator, do we have additional questions?

Your next question comes from Brian Scorny with Bayard.

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

A good question. Thank you very much. Um, maybe Mike and Gaston, Gaston first, perhaps to, to answer that one. I mean, and you know, we're talking hypothetically here because we have no plans at the moment to, uh, to get into this, but, um, Gaston. Yeah.

Um, thank you, Brian. Um, in, in terms of, um, let me just go to the, um, summarize what we've seen with RNAIs so far. So I think RNAIs have been shown to obviously lower S-antigen. Also HPV RNA correlated antigen, E-antigen. And I think we probably have one of the most robust data showing that 79 can also reduce HPV DNA in a very robust and rapid way. So The big question, I think, obviously, is going to be should we continue treating and wait until S antigen becomes undetectable, or can we, before considering 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 antigen and obviously infect the pathocytes 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 HIV RNA and HIV DNA, even with a more sensitive assay, was not sufficient to achieve functional cure, defined as loss of S-antigen six months after endotherapy. So they relapsed very quickly. So in that sense, obviously, that study did not include an RNAi agent. And lowering that standard 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. Great. Thank you.

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?

Yeah, so 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, if their S antigen drops below 100, to actually stop the nook 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 loose 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-algin below those thresholds, which have shown in other instances to be clinically relevant, would they be equally relevant towards functional cure when using RNAi agents, in this case, AB729. 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 AB729 in combination with a new But those are encouraging pieces of information that a large proportion of these subjects have already crossed that 100 IU per ml threshold. Great, thank you.

Your next question comes from Mayak Mantami with Briley.

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 know, you are doing an open label study and also the number of subjects, you know, 60, just looking at other trials, you know, look different. So I'm just curious how, you know, you think about data disclosures here. And again, you know, the off-treatment cure rate, that's specific to your program, but also like, you know, as we look externally, you know, there are different approaches. There's the cold-capsule inhibitor approach. There's the immunomodulator approach. Can you comment, like, just at a high level, what's your perspective on, you know, one versus the other, your confidence level, and just given, like, you know, the challenging of treatment cure rates we've seen so far?

Yeah, 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 two study with 60 virologically suppressed subjects with HPV. And essentially, it's comparing the triple, 729 plus vebicovir plus a nuke versus 729 plus a nuke versus vebicovir plus a nuke. 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, you know, we will be able to, you know, track progress as we go. As to the second part of your question, perhaps, Gaston, I can throw that to you.

Yeah, so hi, Mayak. 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, you know, what our study in collaboration with assemblies is going to be looking at. So basically, we're looking at e-antigen negative subjects who have been suppressed for at least six months with no therapy. And they're going to be rolling into, you know, randomized into three different arms. So obviously there are two arms who 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, you know, there are more details on what you can find in clinicaltrials.gov. So I think it's always important, I mean, at least based on my experience, 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, you know, 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 as being well established in further suppressing HIV 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.

Understood. And then just two more quick follow-ups. PD-L1, oral, any color you could provide on time to IND, and just high-level, why this cannot be used in cancer, for example, maybe by a partner if you don't want to do oncology.

Mike, do you want to take that one?

Yeah. Yeah. Hi, Mike. So, look, we've made great progress in that program, and I'm, you know, very excited and optimistic about achieving a clinical candidate nomination in the foreseeable future. And, you know, as I said, you know, from discovery, you know, it's hard to give specific timelines. We want to make sure we bring forward the very best compounds, so we're clearly doing you know, 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, you know, I think we will look at all options on how to exploit the, you know, these other areas in the future. But right now we're really focused on hepatitis B applications for these PD-L1 inhibitors.

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

Yeah, 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... the patent case that was announced last year where there was a challenge against one of our Arbutus patents and was found in our favor. And I think as we've described at the time and subsequently in our various listings, that patent is one of those that has been licensed out to Genovant, which Dave described in his comments this morning. So, unfortunately, it's really not possible for us at Arbutus to comment on what Genovant may or may not be doing. Suffice to say that as part of that license out arrangement, you know, we've got some very clear terms for any sub-licensing that Genovant may do, which is what Dave summarized in his comments. So, I think that's about it. all that we can say. Dave, unless there's any other additional comments you can think of?

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

Okay, great. Thank you. All righty.

Your next question comes from Kalichi Chakiri with Jefferies.

Good morning. Yes, thank you. Yes, good morning, and thank you for taking my question. I guess in respect to the two Phase II combo studies slated to start later this year, Can I ask you to speculate on what are some of the investigational or approved agents you're thinking you could potentially pair with 729? I think we're all aware of Interferon may be something. What are some of the other agents you're thinking of? Any color there would be great. Thank you.

Yeah, 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, you know, our overall hypothesis that, you know, we want to be able to suppress DNA. We want to be able to suppress surface antigens. 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. Gaston, anything you want to add?

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 as antigen to give the immune system, using different approaches as Bill outlined, to reawaken and continue the job of clearing the infected hepatocytes. But we really believe that that lowering of exogenous 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, you know, what the different modalities that we're considering. Got it. Got it. That's helpful.

Thank you.

Your next question comes from Roy Buchanan with JMP Securities.

Thanks for taking the question. Just a quick one. Sorry if I missed this. Any additional details on the RNA destabilizer you can provide? I mean, are you targeting the HDV RNA itself? Are you targeting the host protein? Any additional details? Thanks.

Mike? Hi, Mike. Hi, Roy. So we've actually described pretty extensively some of the mechanistic features of how the molecules that we are working with work. 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. 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 the poly A tail or truncating of the poly A tail that ultimately leads to degradation of HBV RNA. So it is a HBV RNA targeting modality, but it goes via a host protein that's critical for maintaining the stability of HBV RNA. Okay, great. Thank you.

Your next question comes from Key Nikkei with Chardon.

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

Yeah, Gaston, maybe you can take that one. I don't want to be vague in the sense that, you know, we haven't released that in our guidance. But, you know, some of those cohorts have been ongoing for quite some time. I think we just need to make sure that we have, you know, an effective and a realistic timeframe to comment on. And by that, all I'm meaning is that you know, if you give something monthly, then within six months, you've got six doses. But if you give something every 12 weeks, within that same timeframe, you've got many fewer doses. So we just want to make sure that we've got, you know, an appropriate number of doses to comment on. Gaston, anything else you want to add?

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 mg every four and 60 mg every eight weeks, as we pointed out in our guidance. So, I mean, without counting the doses, the goal would be to be able to report, you know, endotherapy for both. So 48 weeks of treatments.

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

That would be the goal to report end of therapy. And then obviously pending decision around, as we were discussing earlier, pending decisions around who can and who cannot stop later on report on basically what happens of therapy in those that may qualify to stop. And that would 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 dosing frequencies. The study was amended in such a way that patients, upon reaching the end of the six months, can re-consent if they decide, and the investigator decides, towards continuation for a national 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 seven to nine and remaining on the node. So as all of these cohorts mature and they progress, specifically to your question for cohort E and F, being the 60 every four and 60 every eight, the next goal would be to be able to report endotherapy. Is that helpful?

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

Yeah, okay. It's not so much that I think we pushed that out. That was one of the later cohorts to start. So it's just taken longer to go through.

Okay.

Thanks.

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

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 II combination clinical trial to evaluate 729 in combination with the assembly biosciences core or capsid inhibitor, Vibicorvia, 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 two combination clinical trials in HPV 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.

Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.