Arbutus Biopharma Corporation Q1 FY2024 earnings call

• Mike McElhaugh announced the end-of-year retirement of Co-Founder and Chief Scientific Officer Dr. Mike Sofia and discussed the Q1 financial and corporate update press release, highlighting achievements in advancing the pipeline for a functional cure for HBV.
• Karen Sims reviewed clinical programs, including preliminary data from the Phase 1a/1b clinical trial with AB-101, details of Phase 2a trials with imdusiran combinations, and the new Phase 2a trial with imdusiran and durvalumab.
• David Hastings provided financial update: ended Q1 2024 with ~$138M in cash, cash equivalents, and investments; received net proceeds from share issuance; expects 2024 net cash burn between $63M and $67M; cash runway sufficient to fund operations through Q2 2026.
• Mike McElhaugh gave an update on patent infringement litigation, including the Markman hearing result in the Moderna lawsuit and trial dates, and ongoing litigation with Pfizer/BioNTech.

No detailed financial segment performance by product segments with absolute revenue and contribution % provided in the transcript.

• Expect 2024 net cash burn to range from $63 million to $67 million, excluding proceeds from ATM program.
• Anticipate reporting end-of-treatment data from AB-729-201 and 202 Phase 2a trials at EASL in June.
• Look forward to preliminary end-of-treatment data from the nivolumab arm of the AB-729-202 trial in the second half of 2024 and preliminary multiple ascending dose data from the healthy subjects in the AB-101 001 trial in the second half of 2024.
• Cash runway is sufficient to fund operations through the second quarter of 2026.

• Ongoing patent infringement litigation with Moderna, including fact discovery and a trial date set for April 21, 2025 (subject to change).
• Pfizer/BioNTech lawsuit ongoing with no set date for claim construction hearing.

Q: Hi, good morning. Thanks for taking our questions. Two, if I may on the pipeline. You guys have a few Phase 2 trials with a lot of different combinations going on, but how about one thing we can get any functional cure signals? Is that 2025 types of events, or can we get some data later this year? And then number two, I appreciate you starting a new Phase 2 with durvalumab, but I'm just curious, how much more data do you think you'll need from your hepatitis B trials before you can start a Phase 3? I'm just wondering what is the gating factor here? Is it waiting for AB-101 to show some combo data or the data from the new durva study, which is essentially one year treatment and one year follow-up?

A: Good morning, Dennis. Thanks for the question. Karen, do you want to handle Dennis' first question on functional cures? Karen Sims: Yes, sure, absolutely. Dennis, as you know, as you just stated, these trials do take some time, including the treatment period and the follow-up period. As you know, functional cure signals can't be assessed until subjects are at least six months off of all treatment. So that is ongoing in both of our Phase 2 studies at the moment, both the 201 interferon study and the 202 study in combination with, for instance, VTP-300. So as the data comes in and as we are able to, few compile that data into a meaningful data release with a sufficient number of subjects, we'll certainly show that when we can, so I can't give any additional guidance just to say that the trials are ongoing and we'll present the data as it becomes available. Mike McElhaugh: Okay and then on to the second question was in regards to the durvalumab and when we might be able to start a follow-on trial. I think the answer to that question, Dennis, is it's going to depend on what we see from our existing ongoing studies right. So, yes, we're starting a new trial and yes, we think that will be valuable and helping to inform how we think about the addition of AB-101 to imdusiran but as Karen just mentioned we have some trials ongoing which could of course produce interesting data which could then lead to follow-on study. So I don't think that it's a situation where we need to wait until we have the full picture from all of these trials ongoing before we decide what we're going to do to move forward. As you know, the goal here is functional cure, if we can deliver some functional cures than any of the ongoing studies, we will obviously be moving that as quickly as possible into follow-on studies.

Q: Hi, good morning, everyone. This is Thomas Yip asking a couple of questions for Ed. Thank you for taking the questions. So first, perhaps following up with the previous question, just looking forward for imdusiran, with the next Phase 2b or Phase 3 study, would that be expected to evaluate imdusiran as a monotherapy or in a combination or perhaps both?

A: So, Thomas, good morning. Thank you. This is Mike. I think we've always said that we're going to have to think about combination therapy when it comes to curing HBV. We have to cater three pillars that we talk about frequently. So I think as we think about what a next study might look like, it's definitely going to be a combination study.

Q: Understood Perhaps one question for Dr. Sims for the new Phase 2a study with durvalumab. Can you discuss the rationale behind different dosing intervals for durvalumab and what is the significance to analyze these different dosing intervals?

A: Yes. Thanks for the question, Thomas. So the idea here is evaluating the extent of checkpoint inhibition that's necessary to try to induce that HBV-specific immunity. So as I'm sure you're aware, the use of checkpoint inhibitor therapy in oncology is a much different dosing regimen and much different dosing levels, so it's very high doses over repeated cycles for weeks to months, and with that comes a safety profile that may not be optimal in patients with chronic hepatitis B. So what we're looking to do is strike the appropriate balance between having a regimen that's safe and well tolerated for these patients with chronic hepatitis B, as well as trying to understand exactly when we need to intervene on the checkpoint inhibitor access in the context of the surface antigen reduction that we see with imdusiran. So that's the idea behind the trial, is it best to inhibit the checkpoint access during the acute decline of surface antigen, is it best to inhibit after surface antigen has reached a nadir somewhere in between and doing that at multiple time points. So that's the idea behind the trial, is to really just strike that balance between optimal immunomodulatory effects but maintaining a very good safety profile for this patient population.

Q: Understood. Thank you. And perhaps one last question for AB-101. After completing the multi-ascending dose Phase of the ongoing Phase 1 study, what's the next step for the program? Would that be looking at a combination study in HBV or are there other therapeutic areas that AB-101 can have potential in?

A: Sure, yes, thanks for the question. Again, just to clarify, so the current study is a three-part study, so single doses in healthy subjects, then multiple doses in healthy subjects, and then we move seamlessly into multiple doses in patients with chronic hepatitis B in combination with nuke therapy. So we need to complete those different portions of the trial to understand the safety profile, the pharmacokinetic profile, the PD profile of AB-101, to be able to enter that next Phase of studies. But certainly you can imagine after completion of the Phase 1 study, the next goal would be to put it in combination with imdusiran in a Phase 2 study as quickly as possible.

Q: Hey guys, thanks for taking our question and congratulations and best wishes to Mike. This is Charlie on for Brian. So just a couple from us, just wondering when you're thinking about dosing with AB-101, it sounds like so far, you've seen good safety data, but just would be curious if you're kind of thinking of 25 mgs as a cap in the med as well. And then, are you, when you're thinking about this, the durvalumab trial, have you seen anything from the nivo combination so far that might be playing into your thinking on different timings? And then just one more on an early stage asset in the space. What are your thoughts on ALPK1 agonism, if you have any at this point?

A: All right, so, Charlie, good morning. Thanks for the questions. So, Karen, why don't you handle the question with regards to AB-101 and the nivo laid to durvalumab question? Karen Sims: Yes, sure, absolutely. So the data we're sharing thus far is just the extent of dosing we've completed with AB-101. So it's too early to comment on the dosing that we'll be using in the next portions of the trial. We do have flexibility in the trial in all the different arms to either increase dose, decrease dose, make changes to dosing regimens. So 25, as reported today, is the highest dose we tested with an excellent safety profile and good pharmacodynamic profile. So we'll be evaluating different dosing levels as we move on through the trial. So 25 isn't necessarily a cap. It's just the data we have available to share with you today. So and in terms of the nivolumab data coming out of the 202 study, obviously, I can't comment on that. We've provided guidance that we'll be sharing the preliminary end of treatment data at the end of the year, the second half of this year. So that data I can't comment on, but certainly we look at all of our trials holistically and certainly would, as Mike said earlier, move forward or adapt as we see the data emerging with our trials. But yes, to date, I can't comment on anything regarding the nivolumab arm and the 202 study. Mike Sofia: Yes, on the ALPK1 question, yes, we're aware that an abstract just came out on EASL on that. Frankly, it just came out. So we are interested in looking at the abstract more clearly, more fully, and obviously seeing the presentation EASL to get a full understanding of the target.

Q: Hey, thanks for taking the question. Obviously, congrats to Mike Sofia on the planned retirement, and he definitely misses. Deep insights and observations on the calls. You have eight months to get to a functional cure now. Just a few questions. Just so, I guess on the 203 trials, I think there's a typo on the slide that says Q48 weeks, and I think Karen said every eight weeks, which makes a lot more sense. So I just want to confirm that. And then, I guess it's the only variable that the timing of durvalumab dosing, there's no other -- the arm's all identical. So is that the only variable? There's no difference in actual dose levels or anything else. I guess that's my first.

A: Yes, no, thanks for the question. So you're absolutely right. The imdusiran dosing is 60 milligrams every eight weeks, as we have been studying throughout our Phase 2 program. So we'll go in and make sure that's correct in the deck. But yes, 60 milligrams every eight weeks of imdusiran for a 48-week treatment period, as we've also done in some of our other studies. And at the moment, yes, the only difference between the arms is the timing of the imdusiran dose. And as I mentioned before, we obviously keep track of the data with these trials, especially safety data. But we have no intention of changing any of the other parameters of the trial at the moment, just as mentioned, between the three arms. It's just the timing of the two durvalumab doses.

Q: Okay, great. And then follow-up on the 101 dosing question. So if 25 makes per day the dose you started part two with. And then for the, I guess, the target engagement, I assume that was derived from, did you take circulating blood cells? Or what did you look for the target engagement in the patients?

A: Right. So in regards to the dosing of AB-101 in part two of the study, again, I can't comment on that. It's ongoing as we speak. And as Mike said earlier in the call, we'll be providing data for the part two portion of the study in the second half of this year. And in regards to the pharmacodynamic assay, yes, it is based on peripheral blood mononuclear cells that are isolated from the subject.

Q: Okay, great. And then the last one, maybe you can't answer this either, but it's on the nivo combo with Barinthus vaccine. Can you give us a sense? It looks like the enrollment target went up by a couple of patients, 22 versus 20. Can you just tell us where enrollment stands currently in that cohort and about how many patients you can expect for the data in the second half?

A: Sure, absolutely. So the target enrollment was 20 subjects for that arm to be consistent with the other two arms of the study, as often happens in these studies, we have screening open to many sites in many countries across the globe and we can't necessarily control the number of subjects in screening at any one time. So it just happened here that we had a couple of additional subjects that were eligible for the trial and had completed screening, so we did allow them to enter the trial, but that's the only reason for the 22 subjects as opposed to the 20 subjects. And as said previously, we'll be sharing the preliminary end of treatment data from that trial in the second half of this year.

Q: Yes, just some follow-ups on 101 study. In terms of the receptor occupancy, is the assay you're using, is that a standardized or do you have to customize it for this?

A: Hi. This is Mike, Keay. It's an assay we actually developed internally, so it's a proprietary assay that we use for getting that target occupancy readout.

Q: Okay. And is the dose response you're seeing, is that consistent with what you're supposed to see?

A: Well, I would say preclinical models, we see 80% to 100% receptor occupancy. So that gave full efficacy for us. So I think what we're seeing in the clinical study is very encouraging to us.

Q: Okay. And then in the multi ascending dose part of the study, just remind me again, what's the dose frequency? How often is it?

A: So it's a total dose duration of seven days, and we do have flexibility within that arm to dose every day or anything different than that depending on how the data reads out. So it could be a daily dose. It could be every other day, every third day, that part will be determined as we evaluate the safety PK and PD data that comes in from the different arms of the trial. But it's a seven day maximum duration.

Q: Okay. And when do you expect to be able to advance into part three of the study?

A: Right. So it really depends on how these multiple ascending dose arms proceed in the healthy subjects. So really, we just need sufficient, again, safety PK and PD data to feel confident to move into that third portion of the trial and to choose a dose to initiate that part of the trial that we think will have impact in these chronic hepatitis B subjects. So, again, it just depends on the progression of part two of the study. But it is, as we've said earlier, an integrated protocol. So the part three of the study is already approved and we would be able to move on as soon as we are ready with the data. Thank you.