Good day, thank you for standing by. Welcome to the Arbutus Biopharma Corporation fourth quarter and year-end 2022 financial results and corporate update conference call. At this time, all participants are on a listen only mode. After the speaker's presentation, there'll be a question and answer session. To ask a question during the session, you'll need to press star one one on your telephone. You will hear an automated message advising your hand is raised. To withdraw your question, please press star one one again. Please be advised today's conference is being recorded. I would now like to hand the conference over to your speaker today, Lisa Caperelli. Please go ahead. Thank you, Kevin. Good morning, everyone, and thank you for joining Arbutus' fourth quarter and year end 2022 financial results and corporate update call. Joining me today from the Arbutus executive team are Bill Collier, President and Chief Executive Officer, David Hastings, Chief Financial Officer, and Dr. Mike Sofia, Chief Scientific Officer. Bill will begin with a corporate update, followed by Dr. Sofia, who will provide an overview of our newly nominated coronavirus compound, AB-343. Dave Hastings will provide a review of the company's fourth quarter and year-end 2022 financial results. After our prepared remarks, we will open the call for Q&A. Before we begin, I'd like to remind you that some of the statements made during the call today are forward 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 annual report on form 10-K to be filed later today and from time to time in our other documents filed with the SEC. With that, I'll turn the call over to Bill Collier. Bill? Thank you, Lisa. Good morning, everyone, thank you for joining us today. We appreciate your continued interest and support of Arbutus Biopharma. This morning we issued a press release with our fourth quarter and year-end 2022 financials as well as an update on the significant progress we made last year in advancing our proprietary compounds, moving us closer to our goals of potentially achieving a functional cure for chronic HBV as well as a novel and superior treatment for corona. We also highlighted our anticipated milestones for 2023, which include announcing AB-729 data from our two ongoing phase 2a combination trials and additional off treatment data from our phase 1b clinical trial. We also intend to initiate in 2023 three phase 1 clinical trials with our early stage compounds, namely AB-101, our oral PD-L1 inhibitor, AB-161, our oral RNA destabilizer, and AB-343, our newly nominated Mpro main protease inhibitor in development for coronavirus infection. Suffice it to say, 2023 will be a busy year for us, with potentially four compounds in the clinic by the end of the year. With respect to our mission to achieve a functional cure for patients with chronic HBV, we believe it's necessary to suppress HBV DNA, reduce surface antigen, and boost the immune system. Data that we generated last year from our phase 1b clinical trial tells us that AB-729 can potentially achieve all three of these goals. This sets AB-729 apart from other RNAi therapeutics in development. First, AB-729 has shown reawakening of HBV specific immunity as well as a decrease in exhausted T cells in some patients. In addition, a small subset of patients who met eligibility requirements to discontinue all HBV therapies following AB-729 treatment were able to control their HBV biomarkers while off treatment. Surface antigen levels in those patients remained well below pre-trial levels. Furthermore, their HBV DNA remains low, suggesting establishment of host immune control. Now, these data reinforce our belief that AB-729 is one of the most advanced RNAi therapeutics in development and that it has the potential to be a cornerstone therapeutic in the treatment regimen for chronic HBV. Which leads me to our 2 ongoing phase 2a clinical trials with AB-729. One in combination with interferon and one in combination with Vaccitech's therapeutic vaccine, VTP-300. At the end of 2022, we completed enrollment and announced preliminary data from the lead-in phase of AB-729-201, the phase 2a clinical trial with AB-729 in combination with ongoing nucleoside analog therapy and short courses of interferon. The first 15 patients who reached week 16 of treatment after receiving 2 doses of AB-729 on day 1 and week 8 plus nuke therapy showed a mean surface antigen decline of 1.5 logs, which is comparable to the decline observed at the same time point in our phase 1b clinical trial. These preliminary data further validate AB-729's capacity to reduce surface antigen. As patients complete the lead-in phase, they are being randomized to receive interferon plus nuke therapy plus or minus additional AB-729 doses for either 12 or 24 weeks. We expect to have preliminary data from some of these patients who have received interferon in the first half of 2023. Our second Phase 2a clinical trial AB-729-202, which is evaluating AB-729 nuc therapy and VTP-300 or placebo, is being expanded to include an additional arm with low dose nivolumab, which is a PD-1 monoclonal antibody inhibitor that's approved for a number of types of cancer under the brand name Opdivo. We are adding nivolumab, more commonly known as nivo, to determine if the addition of nivo to the VTP-300 combination will further stimulate immune mediated reduction of surface antigen after the initial treatment with AB-729. This amendment is currently under regulatory review. On regulatory approval, we intend to enroll 20 patients on ongoing nuc therapy who will receive 60 milligrams of 729 every 8 weeks for 24 weeks, followed by VTP-300 plus a low dose of nivolumab. The nivo dose that we will use is one-tenth the dose approved for oncology indications, which we believe to be safe yet efficacious. Patients will remain on their nuc therapy during this 48 weeks of dosing with 729, VTP-300 and nivo. Like all our trials, we will follow patients for 24-48 weeks after completion of the treatment period. As a reminder, dosing in this amended portion of the trial is expected to commence in the first half of 2023, and preliminary data from the original portion of the clinical trial, that is, those patients who received 729 nuc and VTP-300 or placebo, is expected in the second half of 2023. To round out our HBV assets, last year we nominated and conducted IND enabling studies with AB-101 as our oral PDL1 inhibitor and with AB-161 as our oral RNA destabilizer. Both of these programs could play a role in developing a proprietary all oral combination therapy to provide a functional cure for patients with chronic HBV. We are on track to initiate phase one clinical trials with each of these compounds, and we expect to report initial data this year. We'll share more details when each of these trials commences. Finally, as Dave will reiterate in a moment, we are in a strong financial position with cash runway into Q4 of 2024. I'll now ask Mike Sofia to review our progress in the coronavirus. Over to you, Mike. Thanks, Bill. Good morning, everyone. For the past year, the Arbutus research team has relentlessly focused on identifying and developing new antiviral small molecules to treat COVID-19 and future coronavirus outbreaks. Many question whether there would be a need for new or more therapeutics for coronaviruses. I believe we can all say that the need exists as the virus continues to mutate, spread, and reinfect. Our strategy focuses on targeting 2 essential enzymes critical for viral replication and that are highly conserved across all known coronaviruses. These 2 targets are the SARS-CoV-2 NSP5 main protease, also known as Mpro, and the NSP12 viral polymerase. We plan to identify compounds that target each of these essential enzymes, develop those compounds, ultimately combine them to pursue an optimized treatment regimen that is safe, effective, convenient, and able to address current and future coronavirus strains. Through our research efforts, we have discovered and nominated AB-343, an Mpro inhibitor, as our lead oral coronavirus drug candidate. We selected AB-343 based on its preclinical activity, safety profile, and the potential for convenient dosing. From an activity standpoint, AB-343 is highly potent with an IC50 against the enzyme in single-digit nanomolar. It has equipotency against all known SARS-CoV-2 variants and robust activity against known Mpro resistant variants. With respect to safety, AB-343 is highly selective for coronavirus Mpro versus human proteases. It also has a clean, broad cellular toxicity profile and off-target assessment profile. These characteristics support the reduced potential for unwanted side effects, thus further supporting candidate nomination and justification for progression into development. Equally important to developing a drug that is safe and efficacious is to ensure that the drug is convenient for patients and physicians. Based on the preclinical PK data, AB-343 does not require enhancing with ritonavir boosting. This could lead to decreased pill burden and reduced potential for drug-drug interactions seen with ritonavir boosted regimens. I am impressed with AB-343's preclinical profile and excited to move it forward into IND-enabling studies with the intent of initiating a phase I clinical trial in the second half of this year. As I mentioned in my opening remarks, we are targeting two essential enzymes, the second one being NSP12 viral polymerase. Our research team is closing in on its efforts to identify the lead candidate we can then take into IND-enabling studies in the second half of this year. We will provide an update when that compound has been identified and nominated. I will now turn the call over to Dave Hastings for a brief financial update. Dave? Thanks, Mike. Good morning, everybody. As I've mentioned in the past, our key financial metrics are cash and financial runway. Our cash equivalents, and investments were approximately $184 million as of December 31, 2022, as compared to approximately $191 million as of December 31, 2021. During the year ended December 31, 2022, the company received a $40 million upfront payment from Qilu Pharmaceutical Company related to a technology transfer and license agreement for AB-729 in Greater China. $15 million of gross proceeds from Qilu's equity investment in the company and approximately $20 million of net proceeds from the issuance of common shares under Arbutus' at-the-market offering program. These cash inflows were partially offset by approximately $79 million of cash used in operations. The company expects the net cash burn, a net cash burn of between $95 million-$100 million in 2023 and believes its cash runway will be sufficient to fund operations into the fourth quarter of 2024. Additionally, we were pleased to see that OMERS, who we sold our primary royalty interest in ONPATTRO to, now has earned $18.9 million in cumulative royalties. As a reminder, once OMERS collects $30 million in ONPATTRO royalties, that entitlement will revert back to us. After that reversion, our royalty rate is tiered, with the top tier being slightly over 3% for annual net sales greater than $500 million. In closing, we are well-positioned financially to advance our mission to develop a functional cure for HBV and a treatment for COVID-19 and potential future coronavirus outbreaks. With that, I'll turn the call back to Bill. Thanks, David Hastings. Before our Q&A session, I want to just quickly remind everyone of the key milestones that we anticipate for 2023. They are as follows: We plan to report initial data from the phase 2a clinical trial combining AB-729 nuc therapy and VTP-300 in the second half of 2023. Antidote the first patient with nivo in the clinical trial amendment that combines AB-729, VTP-300, plus nivo. We also plan to announce preliminary interferon data from patients in the AB-729-201 clinical trial, who receive AB-729 plus therapy plus interferon. We plan to announce additional off-treatment data from our AB-729 phase 1b trial. We plan on reporting initial data from the healthy volunteer single dose portions of our phase 1 clinical trials for AB-101 and AB-161. Finally, we plan to initiate a phase I clinical trial for AB-343, our Mpro coronavirus clinical candidate. We look forward to providing you with updates as we progress our clinical development and achieve these milestones. Operator, we're now ready for our Q&A session. Over to you. Ladies and gentlemen, if you have a question or a comment at this time, please press star one one on your telephone. If your question has been answered or you wish to move yourself from the queue, please press star one one again. One moment for our first question. Our first question comes from Dennis Ding with Jefferies. Your line is open. Hi. Thanks for the questions. Two for me. In terms of your corporate strategy this year, maybe comment on what your priorities are and how to balance your pipeline versus, you know, finding some BD opportunities with your broad pipeline. My second question is just around, you know, when you talk with potential partners in the space, for Hep B, generally speaking, what level of clinical risk do you think partners would be comfortable with? What do you think they would wanna see before potentially advancing discussions with you? Thank you. Thank you, Dennis. Let me take the first part of the question, and then I think Mike McElhaugh is on the line, and he can take the second piece. We believe actually we've made a number of adjustments in our strategy in the last year or so in order to focus in on HBV and coronavirus. That includes making some pretty tough decisions. You'll notice today we've said nothing about capsid inhibitors going forward. That's an illustration that, you know, we believe we have a very good compound in 729. We're confident in moving 161 and 101 into the clinic, which could round out a very nice HBV portfolio. As Mike just described, you know, spending some of our resources on coronavirus, we believe is still very relevant given the ongoing epidemic and pandemic around the world. We've been able to do all of that whilst extending our cash runway out to the end of 2024. We feel like we have made some tough choices and prioritized appropriately, but still maintaining, you know, a real tight focus on our vision in trying to find a functional cure for HBV and an effective treatment for coronavirus. Mike, are you okay taking the second part of the question? I am. This was the one that is related to, what level of clinical risk is relevant? Yes. Correct, Bill? Well. Yeah. Dennis, thanks for the question. You know, as we've discussed in the past, we have conversations with everybody in the field, frequently, at all the, you know, at all any conference that we're at where there's people. You know, I reach out to people all the time in regards to the BD work that needs to be done. I'm always having conversations with people. As far as, you know, as far as what level of clinical risk is, you know, is sort of their guideline, they, you know, they don't really tell me that. I think it's variable depending on who you're speaking to, whether you're speaking to a large company or a small company. You know, I think, you know, we just have to let the data evolve and see how those conversations progress. We'll continue to have those conversations. Got it. Thank you. Thank you, Dennis. One moment for our next question. Our next question comes from Brian Skorney with Baird. Your line is open. Hey, good morning, guys. This is Charlie on for Brian. I was curious if there's anything we can look for beyond safety to get a good grasp on potential activity for either the oral PD-L1 or the RNA destabilizer. As well as looking at 729, with one of the patients becoming eligible to restart new therapy. We're just curious, you know, what kind of proportion would you be looking here for the remaining patients in terms of defining success for you guys? Thank you. Yeah. Okay. Good question. Maybe, Mike Sofia, would you like to talk about AB-161 and AB-101? I'll come back on AB-729. Sure. Thanks, Rolly, for the question. When we look at our oral PD-L1 inhibitor AB-101, obviously, you know, we're looking at safety as our first in readout in the phase 1a studies. We can also actually gain some insight on how this molecule is working and whether we anticipate efficacy when we're looking at. We have several abilities to look at target engagement and target occupancy. From those studies, we'll be able to see whether this molecule is actually engaging the target, and, you know, producing some kind of target-relevant biological readout from the immunology side. That'll give us some early hints on, you know, whether this molecule, you know, is, has the potential to show HBV clinical efficacy as we progress in the phase 1b studies. We'll get that in the SAD/MD portion of the study pretty early, and be able to say something about that, you know, by the end of the year. When you look at AB-161, our RNA destabilizer oral compound, you know, there clearly this field has struggled with safety. Safety is gonna be a big part of, you know, how we assess this very early on. You know, as I've always mentioned, we've done a very extensive preclinical safety assessment based on, you know, our previous knowledge that we gained on AB-452 and the peripheral neuropathy studies. You know, we've done 60-day 2-species toxicology studies. I mean, excuse me, 90-day 2-species toxicology studies to reaffirm our belief that this molecule has a safety profile that we feel confident in going forward in the clinic. That early, you know, obviously phase 1 studies, where we'll be looking at safety pretty clearly and, you know, paying clear attention to some of the signals for the peripheral neuropathy are gonna be important to us. You know, once that's done, then obviously we'll run right into a phase 1B study where we'll be capturing the efficacy aspect of it, you know, the biomarkers and specifically looking there at the antigen reduction and HBV DNA reduction in those parts of the phase 1B study. Bill? All right. Mike. On the 729 follow-up of these 9 patients who are now off of all therapy, I just wanna clarify. We now have 7 patients remaining for follow-up. I wanna just clarify that actually so far, only 1 patient has met the clinical criteria to restart therapy. There was 1 other patient who experienced what looked like some kind of increase in HBV DNA. Before that patient met any restart criteria, the physician and the patient decided to restart therapy. Out of the 9, we only have 1 that's met the predefined protocol criteria for restarting therapy. We remain really intrigued and interested in this data. We think it is well worthwhile following up. We have some interest obviously from physicians and KOLs in continuing to track these patients. You should point out that many of these patients now are multiple weeks into being off of therapy. I think as we've alluded to, we'll track these patients and continue to report data as we progress through 2023. Wonderful. Thank you. One moment before our next question. Our next question comes from Thomas Yip with H.C. Wainwright. Your line is open. Hi. Good morning, everyone. Thomas asking a couple of questions for Ed. first, a follow-up on the tail of the 7 patients that remain off treatment in the 001 study. Can you tell us what is the range of how many weeks these patients have gone off treatment? How frequently should we expect updates this year from these patients? Yeah. On the update, we've said we'll provide an update in the first half of the year. Obviously, as we continue to progress during the year, if there's further news, then we'll provide further updates. I am actually having to work from home today. You can tell I have a pretty horrendous head cold. I actually don't have the data for the number of weeks of therapy in front of me. I just wonder if there's anyone else on the call who has that information. I don't know whether Mike McElhaugh or Mike Cecere. I'm also just looking back on the deck here. Yeah. Give me just one second, Bill. Yeah. let's see. Patients have been off therapy, as of the last data update at least, patients have been off therapy anywhere from sort of, let's see, 2 to 20... Call it roughly 20 weeks to 44 weeks or more. That's right. As of the last data update, remember. Patients obviously you can continue to track that forward and get a sense for where patients are. Yeah. That, that is slide 13 actually in the corporate deck, which you can see the data for the nine patients, and this was what we reported in December last year. Mike's giving you the range of weeks there, and then we can add on, I guess, a few more weeks since the December update last year. Thank you, Thomas. Right. Yeah. Yeah. As you alluded to, seven patients among the nine. It's been couple of months. Expecting more than 44 weeks, I suppose. Yeah. As you as we continue to see this off-treatment data with more patients, what do you expect some findings that you continue to collect that could impact the ongoing phase 2 combination studies? You mean what data could we expect from these remaining seven patients? What, more specifically, what kind of findings could you expect from these patients that could potentially change or alter any of the phase 2 combination studies that are either ongoing or new cohorts? Yeah. Okay. Understood. Well, I mean, obviously, we wanna continue to track them. I hope that there are not too many more that, you know, meet the criteria to restart treatment, but that's one potential outcome. Another potential outcome is we potentially get a few who do actually go undetectable. We just have to track and obviously we'll report if that does happen. The other outcome is that actually they kind of continue to stay as they are, which is, you know, low levels of HBV DNA, low levels of surface antigen, not meeting the criteria to restart treatment, but not undetectable. Which I think would be a demonstration that actually treatment with AB-729, you know, and the nuc, does actually get these patients to a position where they're able to come off therapy. It might also indicate that, you know, the ultimate combination, the functional cure would be, you know, AB-729 and nuc and then a third agent, designed to, you know, further boost the immune system, which is where our PD-L1 program comes in. That I think would be, you know, interesting information. Obviously we're looking for the same thing in our phase 2a studies, whether or not the addition of interferon and/or VTP-300 plus or minus nivo results in further F antigen reductions than AB-729 alone. Obviously in the follow-up period, we'll be looking to see how these patients respond when they're off treatment. Got it. Thank you so much. Perhaps one final question from us. Speaking of the VTP-300 combination study, what type of preliminary data should we expect to be announced in the second half of this year from this study? Yeah. I think the best way to think about that, and, you know, in our corporate deck, we've kind of laid out the trial designs for both the interferon and the VTP-300 study. We're gonna be in the phase where some of the patients have received VTP-300 or the placebo. Therefore, that's the type of data that we will be sharing later this year. We won't be able just 'cause of the length of the study to report, you know, end of treatment data or follow-up data. It's gonna be somewhere, if you look at slide 18, somewhere in that kind of dark red phase where patients are receiving VTP-300 or placebo. Got it. Thank you so much again for taking our questions. Thank you. One moment before our next question. Our next question comes from Keay Nakae with Chardan. Your line is open. Yes, a couple questions. For the one patient who was off treatment and then restarted, how? Keay, we aren't able to hear you. Yeah. Sorry. Can you hear me now? Yes. A little better. For the 1 patient who was off treatment and then met the criteria to restart, how long were they able to stay off treatment? Can I get back to you on that, Keay? I don't know that I have that information immediately at my fingertips. Okay. Yeah. Bill, I have that available if you'd like. Oh, you do? Okay, go on. The one patient that required restart because of the protocol-defined criteria, discontinued follow-up week 36 after, 36 weeks after they stopped, all therapy. Yeah. Yeah. Yeah, Yeah, thanks, Mike. Okay. That's also on slide 13 in the deck. There's a little asterisk at the bottom. Thank you. Okay. for Mike, for Mpro, as you take that into the clinic, once you get beyond safety, and want to evaluate it in patients who may have the virus, what might that study look like? What would be maybe a targeted course of therapy? You know, is it gonna be like a five-day, like a Paxlovid? Maybe give us some thoughts about that. Yeah. Thanks, Keay. Keay. I think the... You know, we haven't really sort of communicated what our clinical development plan is gonna be. You can imagine based on what, you know, what some of our competitors have done in the field, you know, we would be looking at potentially, you know, readouts that would look at viral load decline. They could look at reduced hospitalization. One of the things that we're really quite interested in as we go forward is, does this molecule or ultimately our combinations produce any effect on reduction in symptomology or potentially pre-exposure prophylaxis? Those are the kinds of things that we're targeting and sort of mapping out our clinical development plan and, you know, eager to get those started as soon as possible. Okay. Once you have the second compound ready to go into the clinic, how soon would you evaluate it as a combo therapy, at least in terms of safety? Well, I mean, you know, we could do some preclinical assessments to look at combination safety. We do a lot, a lot of that sort of in, let's say, in the preclinical environment. Once we get, you know, our second molecule nominated and moved through IND-enabling studies, we'll do our, you know, phase one compound with the single agent. We have to certainly, based on, you know, previous developments in the antiviral field, we'll have to show that it works and is safe by itself. Then as rapidly as we possibly can, assuming all those ducks line up, we'll get it into combination. you know, right now, you know, we're looking at, you know, hopefully a fairly short early clinical development program because of a short duration of therapy that you need to show some kind of antiviral effect. and that hopefully will accelerate our ability to get into combinations. Okay. Just a final question on the litigation with Moderna. Is there any update you can provide as far as a next step in that process? Yeah. Thank you, Kay. unfortunately not. we're gonna stick to our policy that we've had since we filed that case last year. We just don't comment on the ongoing twists and turns of the case. you know, you didn't see any updates in our press release or our prepared remarks. although frustrating for you guys, which I understand, that one's a no comment. Okay. Well, very good. Thanks. Thank you so much. One moment for our next question. Our last question comes from Roy Buchanan with JMP Securities. Your line is open. Hey, thanks for taking the questions. I had a few for COVID first, I guess. 343 looks very potent. Do you anticipate once daily oral dosing? When do you think we might see the preclinical data first presented for that? And then the IC50, presumably that's in vitro and not cell-based, can you give us any details on what system that was? Thanks. Mike? Well, yeah, our PK. We have 1 presentation that's gonna be at ICAR this year in a couple weeks that will highlight, you know, sort of the entire in vitro profile of the molecule itself. We anticipate submitting a couple of abstracts at other meetings coming up in the very near future to also share, you know, preclinical data that we have on the molecule. Hopefully some of that will be rolling out, you know, shortly for everyone to see and you know, see what an exciting molecule we have in AB-343. Okay, great. Any comments on the once daily dosing? I can say our PK looks very good. You know, we in multiple species. We're just have to see, you know, once we get into clinic what the, you know, dosing frequency needs to be. Right now we're pretty optimistic. Yeah. Okay. Great. On the AB-729, can you just remind us the criteria for restarting the nukes for that patient that had to restart? What's the criteria? Yeah, good question. I can follow up later if it's not. Yeah. Yeah. No, I think that one is not on the slide. That's what I was looking at. Right. We'll follow up with you. Okay. Yeah. Okay, great. I had, so it looks like GSK is limiting in the, in the bepi, phase 3s, the primary endpoints, baseline S antigen below 1,000. Looks like maybe that's 15%-20% of the population in their phase 2b. Is that consistent with kind of your view of the overall CHB population? Look, it looks like pretty much all the patients that you have off therapy, except maybe one, were above 1,000. Is that? Am I looking at that correctly? Thanks. Good question. I don't know that I can comment on the GSK trial. The nine patients that we had discontinue, I think, had all sorts of historic, starting S antigen levels. We can get that information, though, for you, Roy. Right. Yeah, I was just looking at the AASLD presentation. It looks like maybe one's below 1,000, but the rest look like they're above. Okay. Then I get, I guess, just for the interferon combo readout this half, I know you guys have been asked this before, just what are we key points that we should be looking out for for that data? Thanks. Yeah. I mean, as I said in my prepared remarks, I mean, I think the key thing that we would want to see is a further reduction in HBsAg. You treat with 729, and then there's, you know, potentially after you add in these other agents, a further reduction in HBsAg, you know, which could be reflective of, you know, immune response. I will add the caveat that, you know, we've seen in other studies that that doesn't necessarily happen immediately with interferon. Sometimes it takes a while, sometimes it's after the interferon therapy is stopped. We'll have to see how our data pans out and, you know, we'll make the appropriate commentary when we when we do that update. Okay, great. Thank you. Thank you, Roy. Ladies and gentlemen, this conclude the Q&A portion of today's call. I turn the call back over to Bill for any closing remarks. Well, thank you very much for joining us this morning. I'm also thankful my voice managed to hold out. We do appreciate your continued interest in Arbutus, and we especially look forward to providing you with further updates as we progress the development of our HBV and coronavirus assets. Thanks again for joining. Operator, that concludes our call. Ladies and gentlemen, this does conclude today's presentation. You may now disconnect and have a wonderful day.