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spk01: Ladies and gentlemen, thank you for standing by, and welcome to the Abrutus Pharmaceutical BioPharma Corporation 2021 Third Quarter Financial Results Conference Call. At this time, all participants are in listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 1 on your telephone keypad. Please be advised that today's conference is being recorded. If you require further assistance, please press star zero. I would now like to hand the conference over to Lisa Caporelli, Vice President of Investor Relations. Please go ahead.
spk04: Thank you, Angie. Good morning, everyone, and thank you for joining Arbutus' third quarter financial and business update call. Joining me today from the Arbutus Executive Team are Bill Collier, President and Chief Executive Officer, David Hastings, Chief Financial Officer, Dr. Gaston, PTO, Chief Development Officer, and Dr. Mike Sophia, Chief Scientific Officer. Bill will begin with a review of recent accomplishments and clinical developments, followed by Mike Sophia, who will provide an update on our research efforts with an oral PD-L1 inhibitor. Dave Hastings will then provide a review of the company's third quarter financial results. After our opening remarks, we will open the call up for Q&A. Gaston Piccio will be available to address clinical development-related questions at that time. Before we begin, we'd like to remind you that some of the statements made during the call today are forward-looking statements, which are subject to a number of risks and uncertainties, that may cause our actual results to differ materially, including those described in our most recent annual report on 10-K, quarterly report on Form 10-Q, and our other periodic reports filed with the SEC from time to time. I'll now turn the call over to Bill. Bill?
spk03: Thank you, Lisa, and thank you, everybody, for joining us today. We really appreciate your interest in Arbutus Biopharma. Now, this morning we issued our third quarter financial and business update press release, which highlights the significant progress we've achieved this year towards our goal, which is to develop a proprietary portfolio of products with different mechanisms of action that, when used in combination, result in a functional cure for patients living with chronic hepatitis B. We're taking a three-pronged approach that's intended to, one, reduce HBV surface antigen, two, suppress HBV DNA, and three, boost the host immune system, and intend to accomplish this with our RNAi therapeutic 729, our oral capsid inhibitor 836, and our oral PD-L1 program, where we recently commenced IND-enabling studies. So I'd like to start by walking through the clinical advancements we've made with this approach, starting with reducing surface antigen with our lead compound, 729, the RNAi therapeutic. As you know, 729 is specifically designed to reduce all hepatitis B viral antigens, including hepatitis B surface antigen. And we're seeing this activity in our ongoing phase 1A, 1B clinical trial. In fact, data to date has shown that AB729 consistently provides a mean 1.8 log reduction in hep B surface antigen, which is sustained over time in patients with chronic HPV. In addition, AB729 continues to show a favorable safety and tolerability profile. Also, in addition to reporting significant drops in S antigen, some 729 patients have shown increased HBV-specific immune responses, which further supports our rationale for combination therapy to include an immunomodulatory agent. Now, next week at AASLD, we will report additional data from additional cohorts of patients in this clinical trial in a poster presentation. And in that presentation, among other things, we will show that 729 repeat dosing remains generally safe and well tolerated. We'll show that robust mean declines in surface antigen were sustained with repeat dosing of 729 with no meaningful differences observed to date between 60 milligram or 90 milligram doses or dosing intervals, which included every 4, 8, or 12 weeks. And we'll also show that S-antigen suppression to levels below 100 international units per mL, which is a clinically relevant threshold which could inform when to stop therapies, is maintained in some subjects up to 20 weeks following the last dose of 729. As we continue to unveil more data with 729, we continue to believe that the drug has the potential to be a cornerstone agent in future HPV combination regimens. Our strategy is to evaluate 729 in combination with our own novel agents and with other approved or investigational agents with complementary mechanisms of action to set the foundation for future trials. Now, we've made great progress in advancing 729 in clinical trial development. This quarter, we initiated and dosed the first patient in our own Phase IIa randomized open-label proof-of-concept clinical trial to evaluate 729 in combination with ongoing standard-of-care NUC therapy and short courses of PEG interferon in 40 patients with chronic HPV infection. Based on clinical data from our Phase I program, we selected 60 milligrams every eight weeks as the dose and dosing schedule for this trial and other trials. We're currently in the process of opening sites, screening patients, and we will provide further updates on this trial when appropriate. And then from a collaboration standpoint, 729 is being evaluated in an ongoing Phase IIa triple combination trial with Assembly Bioscience's lead HPV core inhibitor and a nucleoside analog. Assembly is conducting this trial and expecting to see data in 2022. Also, activities to initiate separate Phase IIa clinical trials with ANTIOS and Vaxitec are ongoing. We expect that the arm that will include 729 in the ANTIOS clinical trial will commence this quarter, and that the Vaxitec clinical trial will initiate in early 2022. Both trials are designed to evaluate a triple combination of 729, a nucleoside analog, and either the ANTIOS or Vaxitec's proprietary agent. I'd now like to move on to the second arm of our approach, that's to suppress HPV DNA with our next generation oral capsid inhibitor, 836. Now, 836 is specifically designed to completely block viral replication in infected cells by preventing the assembly of functional viral capsids. Preclinical data suggests that 836 may have the potential for increased efficacy and an enhanced resistance profile compared to previous capsid inhibitors. Preliminary data from healthy volunteers and HPV patients in our Phase 1A, 1B clinical trial is on track to report out by the end of this year. And these data may support the initiation of a Phase 2 combination clinical trial with our own proprietary compounds. The third arm of our approach is to boost the immune system, which we hope to do with our oral PD-L1 program. for which we recently commenced IND enabling studies. And after my prepared remarks, I'll turn the call over to Mike Sophia to provide more details about this exciting compound. Now, ultimately, we strive to have a convenient all oral combination treatment for hepatitis B patients. And to achieve that, we're progressing our research efforts with an oral RNA destabilizer program. and look forward to providing updates on our lead optimization efforts in 2022. In addition to our efforts in HBV, our internal research program to identify new antiviral small molecules to treat COVID-19 and future coronavirus outbreaks continues to make progress. So as you can see, Despite the challenging impact of the pandemic, the team at Arbutus has been relentless in their efforts to continue the advancement of our clinical and research programs to meet our corporate goals, to address the needs of patients, and to increase shareholder value. I really am very grateful for the team's commitment and dedication to finding a cure for hepatitis B and for the treatment of coronaviruses. So with that, I'll turn the call over to Mike Sophia for an update on our PD-L1 program. Mike.
spk06: Yeah, thanks, Phil, and good morning, everybody. As Phil mentioned, we are focused on a three-pronged approach to developing a cure for chronic hepatitis B, and key to that is to boost or reawaken the immune system. Given this, we have nominated for IND-enabling studies an oral PD-L1 inhibitor that could potentially be an important part of a combination therapy for the treatment of HPV. Let me start with an overview of why we believe the PD-L1 immune checkpoint axis is a viable target for effecting immune reawakening in the context of HPV. It is well established that the immune system in HPV chronically infected individuals is tolerized to the recognition of the virus or infected cells. It is also believed that highly functional HPV-specific T cells are required for long-term HPV viral control in the setting of functional cure. However, HPV-specific T cells become functionally defective and greatly reduced in their frequency during chronic HPV infection. Immune checkpoints, such as PD-1, PD-L1, play an important role in the induction and maintenance of immune tolerance and in T cell activations. It is well established that the PD-1, PD-L1 signaling pathway in immune cells plays a critical role in the human immune response to foreign pathogens. After the initial immune response to a pathogen, an increased expression of PD-1 and its binding to PD-L1 leads to downregulation of the immune response. In cancer biology, the upregulation of the PD-1 PD-L1 axis has been linked to immune tolerance, resulting in the development of several important immune therapies. Similarly, the PD-1 PD-L1 axis has been implicated as having a role in HPV-specific immune tolerance. It has been shown that HPV-specific T cells in the blood and liver from chronically infected HPV patients express high PD-1 levels, and this level correlates with S antigen load. PD-L1 has been shown to be upregulated during viral hepatitis, and PD-1 has been shown to be upregulated on HPV-specific T cells and S antigen-specific B cells. Ex vivo studies using HPV patient blood and liver samples has demonstrated that HBV-specific T and B cell responses are improved with checkpoint blockade. It has been our longstanding strategy to combine agents that reduce the HBV-specific immune-tolerizing antigen, S antigen, with agents that can further reawaken the immune system. Therefore, we hypothesize that one approach to reawaken HPV-specific T cells is to block the PD-1, PD-L1 protein-protein interaction and hopefully break HPV-specific immune tolerance. Support for this approach was observed in preclinical animal model studies where checkpoint blockade in combination with other direct-acting antivirals led to both DNA clearance and sustained viral suppression. Our research efforts have identified a class of small molecule oral checkpoint inhibitors that we believe will allow for controlled checkpoint blockade, enable oral dosing, and mitigate systemic safety issues seen with checkpoint antibody therapies. From this class of small molecule PD-L1 inhibitors, we nominated a lead candidate based on in vitro potency, immune restoration, in vivo efficacy, selectivity, and safety. Let me provide a little more detail in each of these research parameters, starting with in vitro potency. The PD-L1 bioassay EC50 was less than 20 nanomolar, which is competitive with external compounds. With respect to immune restoration, this lead agent displayed primary human T-cell activation in a preclinical model and restoration of T-cell activity for chronic hepatitis B patient samples in vitro. The in vivo efficacy showed favorable pharmacokinetic and anti-tumor efficacy in a preclinical tumor model. From a selectivity standpoint, the agent binds to PD-L1 with minimal binding to off-target in vitro. The agent has an acceptable safety profile based on progressible in vitro safety pharmacology and in vivo mouse tolerability studies. The small molecule PD-L1 inhibitor possesses in vitro intrinsic activity and functional activity both in whole cell systems and animal models that are equivalent to known PD-L1 antibodies. Based on this preclinical work, this compound is now in IND-enabling studies. I'm excited by the advancements that we've made to identify this lead compound, which we believe has an acceptable safety profile and functional activity to play a key role in our combination approach to finding a cure for HBB. I'll now turn to Dave Hastings for a brief financial update.
spk11: Dave? Thanks, Mike, and good morning, everybody. As I've mentioned in the past, our key financial metric is cash and financial runway. Our cash, cash equivalents and investments is $151.9 million as of September 30, 2021. That compares to $123.3 million as of December 31, 2020. Our cash use from operations for the nine months ended September 30th 2021 was $47.9 million, which was offset by $75.4 million of net proceeds from the issuance of common shares under our RATM program. For all of 2021, we expect our aggregate cash use to range from $70 to $75 million, and therefore we expect our current cash runway to be sufficient to fund operations into the second quarter of 2023. With that, I will now turn the call back to Bill. Bill?
spk03: Yep, thanks so much, Dave, and to you, Mike, as well. So, operator, maybe now is the time to open up the lines for the Q&A session.
spk01: Absolutely. If you would like to ask an audio question, please press star 1 on your telephone keypad. Again, that's star 1 to ask an audio question. Your first question comes from the line of Roy Buchanan with JMP Securities. Please proceed with your question.
spk08: Great. Thanks for taking the questions. I want to start on AB836. Bill, you mentioned the Phase I results. I think coming at the end of this year, you think can support the start of the combo Phase II. I just wonder if you could give a little more details maybe what that Phase II would look like. Would you start with an initial 836 plus a nuke only to do dose finding, or would you go straight to a triple combination with your proprietary compounds? Just kind of what would that look like? Thanks.
spk03: Yeah, thank you very much, Roy. Great question. I think we've actually been saying for quite some time that it's always been our aim to have our own, you know, internal combinations. So kind of logically, you know, in our mind, it makes sense to look at a 836-729 and a nuke combination trial. and we'll clearly share more details on that as next year evolves. I think the important point today is to let everyone know that we're on track to deliver those 836 results by the end of the year.
spk08: Okay, great. And then another 836 question. I'm not sure. Probably you're not going to tell me what the chemistry is, but on the slide it says it's a unique chemistry. Maybe you can confirm it's not a HAP or SBA, and I can try to say the names if you want, but I think you guys know what those are. So is that possible you could confirm that? Mike, do you want to take that one?
spk06: Yeah, this is Mike. Yes, I can confirm that it's neither of those.
spk08: Okay, great. Thanks. And then, you know, I had a question. It's kind of early. It's really early, but I wanted to get your guys thinking about... potential pricing for a functional cure. You know, I mean, is there any reason if a functional cure is found that it wouldn't be, you know, priced, let's say, similarly to the hepatitis C cures that were developed? Just give us maybe your thoughts around that. Thanks.
spk03: Yeah, Roy, thank you. I think, as you said in your question, maybe a tad early to get into pricing specifics. But, I mean, there's obviously – you know, benchmarks of existing therapy. You've got, you know, benchmarks across other viral diseases. And, you know, I think beyond that, it's very difficult for us to say. I will add, though, that, you know, one of our strategies, as I've mentioned, to have, you know, all the components of the functional cure within our own proprietary umbrella is kind of relevant here because it allows you to set whatever the price is ultimately going to be without too much worry about economics to a third party or a partner or royalty and so on and so forth. So one of the underpinnings of our strategy to find our own internal combo is not unrelated to your question.
spk08: Okay, great. I'll hop back in queue. Thanks.
spk03: Thank you.
spk01: Your next question comes from the line of Brian Scorney with Baird. Please proceed with your question.
spk05: Hi, this is Luke Herman on for Brian. We were just hoping you could maybe talk a little about the upcoming Reef One data that J&J is presenting at AASLD next week in terms of the implications it has for the field. And given the kinetics of response, what do you think of the stopping criteria at 48 weeks? Do you think that's a sufficient timeframe?
spk03: Yeah, so thank you, Luke, for that question. Let me make a couple of comments, and then maybe Gaston can be available for any additional comments. I think, you know, we've seen the abstract, as have many other people. I think it may still be a little early for us to comment on competitor data until we see the full presentation and hear what Jansen has to say. I will maybe just add, you know, a couple of additional points. Our development strategy is around this three-pronged approach that we've talked about, which would include an RNAI therapeutic, a capsule inhibitor, and immunotherapy. The data that you just referred to, the reef data, includes an RNAI therapeutic, a capsule inhibitor, and a nuke. And so it may be that this further supports our strategy that an immunotherapy is needed in the treatment regimen to show continued improvement. I think a second point to make at this early stage is that it appears that the contribution of the capsid inhibitor in the J&J study may have been insufficient, and we clearly need to understand that more. But our capsid inhibitor, as you've heard on previous calls, 836, unique, and it's differentiated from other capsid inhibitors And in preclinical data, you know, we've shown that therapeutically relevant doses, 836 has increased potency and engages the second mechanism of action. So I think there is, you know, some differences when you look from capsid to capsid. And I think beyond that, we really just have to wait for the presentation next week and, you know, hear what the companies say. And hopefully that will help answer not just your question, but some of the questions that we have as well. So... With that, Gaston, any additional comments you want to make?
spk02: Yeah, thanks, Bill. I think you covered it very well. In regards to the stopping rule, I think it was referenced in the question. I think it's just one approach to stopping rules, a composite, you know, endpoint that they use, which appears reasonable. I think there may be different ones that are going to be used in the field. So, you know, we look forward to see what happens to patients when they're still based on that criteria after the presentation.
spk05: Great. Thank you.
spk01: We do have a follow-up question from the line of Roy Buchanan with JMP Securities. Please proceed with your question.
spk08: Great. Thanks. So I'll start with the easy one, one for Dave. I guess any ATM use since I think the update was the October 8th prospectus was the last one. Have you guys used it since then?
spk11: Yeah, I mean, we'll update everybody during our fourth quarter update in early March on that, Roy. So we'll comment on that at that point.
spk08: Great. Okay, and then a couple maybe more complicated ones, and early again. But, you know, Bill, your response to the pricing question, what are you guys thinking in terms of partnering? I mean, it sounds like you want to retain – as much ownership as possible, but presumably you go to regions like Europe and China. Are you also thinking you're going to retain ownership there, or will you likely partner?
spk03: Yeah, thanks for the follow-up question, Roy. I mean, I think what I was trying to articulate is if we have all of the individual components of a combination underneath an Arbutus umbrella, it gives us more flexibility on pricing. I think the question that you refer to now, which is around, you know, how do we access different markets around the world? Again, at this early stage, you know, what I would say is that we remain open to different strategic approaches. You know, and, you know, our head of BDs and, you know, regular contact with lots of different people. And, you know, my... My general approach is if we feel that a partnership is going to be the right way to access a market or enable us to meet the needs of patients, then that's clearly going to be good for the medicine and good for shareholders as well. It may be that the individual components of the cure remain within the Arbutus umbrella. And potentially, you know, we partner for different geographies, but we have not, you know, clearly not talked about that. And I'm giving you a hypothetical answer to your question.
spk08: Yep. Yep. Still early. Got it. That's helpful. Thanks. And then another early one, but, you know, the regulatory path, what do you guys envision, you know, the phase three and initial approvals looking like? You know, it's potentially 729 going to be approved. as monotherapy with the nuke, or are you going to go for approvals of the combinations? How do you envision that playing out, I guess?
spk03: Yeah. So right now, what we're really focused on are these four different Phase IIa proof-of-concept studies. And so I think it's really important to underline this, that when it comes to our strategy of reduce, suppress, and boost, you can do that with different combinations of agents. And we're clearly testing out that hypothesis in these four Phase IIa studies. So, you know, I think, again, great question, Roy. But I would like to see how 729 as a cornerstone agent performs in all of these studies. and then to move into phase 2B, phase 3, accordingly. But I think you can determine that as we've set out these different proof-of-concept combinations, we are really looking for the combination to move forward to get to us a functional cure. Gaston, do you want to add?
spk02: No, no, thank you.
spk08: I think you covered it well. Thank you. Okay, great. Thank you, guys. Thanks for taking my questions. Thank you, Roy.
spk01: Your next question comes on the line of Ed Ars with HC Wainwright and Company. Please proceed with your question.
spk07: Great. Hi, everyone. Thanks for taking my question. Just one for me. On 836, obviously, data coming up here at the end of the year on your Phase one study and and this would as you mentioned allow for the phase two presumably next year to Really put together your initial combination studies Wondering if You could talk a little bit about the data what you're expecting in particular I Given that 836, as you mentioned, is a unique capsid inhibitor and utilizes a novel binding site within the core protein dimer-dimer interface, I wondered if there was anything that you were looking from that data that could help support the differential profile that you expect. Thanks.
spk03: Yeah, thank you, Ed. So maybe Mike, Sophia first, and then Gaston as it relates to the clinical data. Mike?
spk06: Yeah, thanks, Ed, for the question. So you're right. 836 is what we call our next generation agent, right? And it differentiates itself significantly from earlier generation agents because of the high intrinsic potency it has, but also, as we've commented on many times, the the ability to engage this second mechanism, right? So the inhibition of the replenishment of the pole of CCC DNA, what we believe will be a therapeutically relevant dose. And I think one of the problems with, you know, the first generation agents is that, you know, the activity at the second mechanism was sufficiently less than the first mechanism activity but that, you know, at relevant doses that they could give in a clinic, they just couldn't engage that. So when you do engage that second mechanism, clearly we believe we're going to have, you know, a fairly robust, you know, response against reduction in RNA as well as DNA, which is the primary mechanism. So I think, you know, we're looking forward to looking at that data and, you know, looking at other biomarkers you know, HPV-related biomarkers to see, in fact, that second mechanism, you know, is playing an important role in the capsid space. So, you know, we have a molecule that we're very excited about. It has high liver exposure. So, I think, you know, overall, you know, we're anxious to see the data to see, you know, how all this translates. Gaston?
spk02: No, I think that that's basically it. We're going to be looking at depth and speed of both HPV and RNA expression. And then there's a little bit of a wild card that we may be able to interrogate, which is the activity of the compound against resistant variants. We are not selectively enrolling patients with resistance, but we know that there are resistant variants out there. And if we by chance, enroll some of those, we may be able to also have an early readout as to the activity of this new generation of the inhibitor against receding variants. But that's a little bit something that we cannot control, really. Right.
spk07: Fantastic. Great. Thank you. Thank you, Ed.
spk01: Your next question comes from the line of Kia Nikkei with Chardon. Please proceed with your question.
spk09: Yes, Kay, Nikkei, Chardon. Some questions for Mike on the PD-1. First, Mike, can you point us to any preclin data that you've published on your oral checkpoint inhibitor?
spk06: Well, we haven't published any specific preclinical data on the molecule that we nominated. Right. I can point you to a nature communication paper that we published looking at the very unique mechanism of how the small molecule works relative relative to, let's say, a an antibody. Right. So that, you know, I can point that to you. We recently published that. I think it was the toward the middle end of last year came out. And also in that paper, we show the small molecule that we used, you know, which was an earlier generation agent. It does have that, you know, sort of anti-tumor effect. So we were using an anti-tumor model because that was the most readily available model at the time. We've now subsequently developed, you know, an HPV model that we're looking at molecules in, an animal model. So you can see in that work that we've, you know, these small molecules do have very unique characteristics. both mechanistically and, you know, function very competitively with antibodies.
spk09: Okay. I'll circle back with you to get that. And so then just kind of moving on then to both, I guess, the safety profile, you know, again, relative to an antibody, you know, you should have some advantages there. But how do we then think about it? the safety as you move into combo therapies, and what would you be on high alert to look for there in terms of safety?
spk06: Well, as you know, in sort of the oncology setting, antibody-based checkpoint blockade does have some adverse events associated with that, right? And one of the things we wanted to do was circumvent that. And the concept that we used was really the small molecule concept. And the reason why we believe that this is going to be a solution to the potential adverse events is with an antibody, you have a very long action occurring, right? So you get one dose and, you know, it's sort of on board for weeks and weeks. With a small molecule, we can take advantage of PK-PD relationships. and essentially just dose enough of what we need to give to get the response. Plus, if there's any issue, we can actually remove drug because the PK washout event. So that's one thing. The other thing is we have, as we always do, is look at liver targeting. And so we have drugs that have high liver centric So, you know, these molecules have much reduced systemic exposure that therefore allows us to target HPV versus having sort of that systemic, you know, immune activation that we see with a typical antibody. So, I think, you know, those characteristics of these molecules, we believe, will support a better safety profile. Now, we're out to see that in the clinic. But, you know, I think we're pretty excited about, you know, the overall profile of these molecules and the potential.
spk09: Yeah, I guess where I'm going with that, Mike, is, you know, with the – well, certainly the destabilizer, you know, there were some tox issues, oral compound. So, again, when we get to a point where you're combining these and you're – eventual all oral solution? You know, how should we think about any synergistic toxic issues we might be concerned about?
spk06: Sure. So so obviously each of these molecules work by different mechanism of action. They are different chemical entities in themselves, so they'll have different characteristics. We clearly in all our preclinical and nonclinical studies, or very careful in ensuring that we don't have any drug-drug interaction issues associated with that. Now, you know, we can't predict exactly what's going to happen clinically, but, you know, we do do combination studies and preclinical models to assess the compatibility of these molecules from, you know, from agonist or antagonistic standpoints. We get some sense of safety read on the combination when we do combination studies in vivo. So, you know, I think we're doing all the things that one needs to do to have a sense of confidence that these molecules will perform in the clinic and perform safely. But really, the clinical setting is going to be, you know, the tell-all of, you know, the theory. Okay, well, thanks for that.
spk01: Your next question comes from the line of Kelechi Chikari with Jefferies. Please proceed with your question.
spk10: Yes, thank you, and good morning. I guess a single question for me here. I guess there's ongoing debate as to what the appropriate stopping criteria should be for many of these combination therapies. I was for the new components. Can you opine on and discuss a little bit more about that and what you think the stopping criteria should be? And I guess related to that, with 729, you've demonstrated the ability to increase HP-specific immune responses. Could that potentially be added on as a component of what could be a stopping criteria for your combination studies?
spk03: Yeah, thank you, Kelechi. I'm going to hand that one over to Gaston.
spk02: Yes, hi. So, yeah, great question. I mean, look, I think, as I was just trying to say, I think different groups will come up with different stopping criteria. There is no single, as far as I know, unified stopping criteria. And usually stopping criteria are composite, you know, endpoints. It doesn't just factor, for example, a concentration of S antigen you know, can include S-antigen plus, for example, HPV DNA and ALT criteria. I think we will know which is the most appropriate stopping criteria once we see what happens to the patients after they stop all therapy. And, for example, if one chooses 100 and then we see that there is a high relapse, but, you know, if one chooses 10, as part of the composite endpoint, and there is less relapse, then one can conclude, obviously, that 10 is better than 100. But we're not there yet. We don't have that data. So I think it would be, I mean, for lack of a better term, I think it would be trial and error. I think, you know, we'll have to try different things. There is no even conclusion. straight consensus on how to stop standard of care today with Nook therapy. Some people use different things, but as we repeated a number of occasions, for example, 100 IU per ml in patients who have been for many years on Nook therapy is a criteria that's used especially in Asia. Now, you're right about the You know, what we've observed in three out of five patients that we were able to measure in cohort E of our ongoing 729001 study, the challenge there, if immune reconstitution would be a criteria, it's something that cannot be measured really quickly to make that decision. As you know, these T cell assays are very labor-intensive, require the collection of peripheral blood mononuclear cells, And they cannot be just run like a viral load in an automated way and a standardized way. So I think it's a very good idea. I hope that we can find maybe some surrogate indicators of T cell reconstitution, you know, perhaps something in line with a measurement of soluble cytokines. interferon gamma, you know, comes to mind that can be more readily and rapidly run in the clinical lab in a standardized way. And that will be the challenge I envision of including T cell reconstitution, T cell immune reconstitution to HPV as part of the criteria. Got it. Thank you. That's very helpful. Thank you.
spk01: Ladies and gentlemen, we've reached the allotted time for questions. I would now like to turn the floor back to management for any additional or closing remarks.
spk03: Well, thank you, Angie, and thank you, everyone, for your questions. We really appreciate you joining us this morning and obviously your continued interest in the company. And look forward to keeping you up to date as we continue to move forward to secure achievement of the milestones that we've shared with you today. and those obviously include the announcement of additional data from the 729 Phase 1A1B clinical trial at AASLD and the initial data from our 836 Phase 1A1B trial by the end of the year. So we look forward to being in touch. And, operator, that concludes our call. Thank you.
spk01: Thank you for participating in today's conference call. You may now disconnect your lines at this time.
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