Arbutus Biopharma Corporation

Good day and thank you for standing by. Welcome to the Arbutus Biopharma 2024 third quarter financial results and corporate update. 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 this session, you need to press star one one on your telephone. You would then hear an automated message advising your hand is raised. To withdraw your question, please press star 11 again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your first speaker today, Lisa Capparelli, Vice President of Investor Relations. Please go ahead.

Thank you, Antoine. Good morning, everyone, and thank you for joining Arbutus' third quarter 2024 financial results and corporate update call. Joining me today from the Arbutus executive team are Mike McElhall, Interim President and Chief Executive Officer, David Hastings, Chief Financial Officer, Dr. Karen Sims, Chief Medical Officer, and Dr. Mike Sophia, Chief Scientific Officer. Mike McElhall will provide a corporate update, including an update on our ongoing clinical programs in HBV. Dave will then provide a review of the company's third quarter 2024 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-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 annual report on Form 10-K, our quarterly report on Form 10-Q, which will be filed today, and from time to time in our other documents filed with the SEC. With that, I'll turn the call over to Mike McElhall. Mike?

Thank you, Lisa, and good morning, everyone. I appreciate you joining us today. A few weeks ago, we issued a press release announcing that multiple abstracts highlighting inducer and data were accepted for presentation at the Liver Meeting 2024, which is the annual meeting held by the American Association for the Study of Liver Diseases. Included in the acceptance are two late-breaker poster presentations with their inducer and data from our ongoing Phase IIa clinical trials, IMPROVE-1 and IMPROVE-2. Since that meeting kicks off next Friday, November 15th, and the data are under embargo, we're not able to provide any updates to those trials at this time. I will, however, review at a high level the data that we presented from those clinical trials earlier this year at the EASL conference. Before doing so, I want to take a minute to discuss why we are focused on a functional cure for patients with chronic hepatitis B. Chronic HPV remains a significant global health challenge affecting more than 250 million people worldwide, despite the availability of preventive vaccines and current treatment options. This underscores our mission to address the urgent need to bring innovative combination treatments with a finite duration, such as those that could include our RNAi therapeutic Indusiran to patients as quickly as possible. Currently, the primary treatments for chronic HPV include nucleoside analogs that suppress HPV DNA and immune modulators like interferon. These agents result in a very low functional cure rate. Therefore, combining new and innovative therapies to reduce surface antigen, suppress HPV DNA, and boost the immune system with current standard of care is needed to provide a more optimal functional cure rate for patients with HPV. If a functional cure rate were available for patients with chronic HPV, it could potentially significantly reduce the patient's risk of liver cirrhosis and hepatocellular carcinoma, decrease patient stigma, and eliminate lifelong treatment and burdensome healthcare costs. As we focus on developing a functional cure for chronic HPV, we believe it is first important to lower viral markers such as hepatitis B surface antigen. Our Phase IIa studies are designed to use imduceran to reduce surface antigen as low as possible before administering an immune modulator. We are combining our RNA therapeutic imducerin with two different immune modulators in two Phase IIa clinical trials, our IMPROVE-1 trial, which includes short courses of interferon, and our IMPROVE-2 trial, which includes a combination of a therapeutic vaccine and an anti-PD-1 monoclonal antibody. At the EASL Congress in June, we reported data from our IMPROVE-1 clinical trial showing that the combination of imduceran plus interferon was generally safe and well tolerated. The cohort that performed the best was cohort A1, where HPV patients received six doses of imduceran and 24 weeks of interferon, in addition to ongoing nuke therapy. In cohort A1, 33% of the patients achieved surface antigen loss at the end of imduceran and interferon treatment that was sustained at 24 weeks post end of treatment. We also looked at a subset of patients who had surface antigen less than 1,000 international units per mil at baseline. In cohort A1, 67% of the patients who had surface antigen less than 1,000 international units per mil at baseline maintained surface antigen loss 24 weeks after completion of imducerin and interferon treatment. This is one of the highest reported rates of surface antigen loss achieved by patients with baseline surface antigen less than 1,000 international units per mil. This is a relevant population to assess because published studies have shown that patients with surface antigen loss have better long-term outcomes. As we think about a Phase IIb clinical trial and based on these data, stratifying the patient population to include those with low surface antigen may best position us for success while still capturing a significant portion of chronic HPV patients. At the time we reported the data, these four patients in cohort A1 with sustained surface antigen loss had discontinued their nucleoside therapy. We've been following these patients to assess them for functional cure. As a reminder, functional cure is defined as sustained hepatitis B surface antigen loss and HPV DNA less than the lower levels of quantification, 24 weeks off treatment with or without hepatitis B surface antibodies. We continue to receive positive feedback on these data from key opinion leaders in the HPV field, and we are excited to provide additional follow-up data from this trial at AASLD next week. In June at EASL, We also reported end-of-treatment data from our IMPROVE-II clinical trial that is evaluating the safety and immunogenicity of a 24-week lead-in with Imdusiran, followed by Barenthis Biotherapeutics Immunotherapeutic VTP300 or placebo while continuing nuke therapy. In this trial, Imdusiran lowered surface antigen to levels less than 100 international units per mil prior to dosing with VTP300 or placebo in 95% of the patients. After receiving VTP300 and through 24 weeks post-end of treatment, more patients maintained surface antigen thresholds of less than 100 or less than 10 international units per mil versus placebo. For patients who reached this time point, a statistically significant difference was achieved in mean surface antigen levels between the treatment arm and placebo. Recall that we have expanded this IMPROVE-2 clinical trial to evaluate the addition of a low dose of the anti-PD-1 monoclonal antibody, nivolumab, to the Mduceran and VTP300 combination treatment regimen, which we believe may further boost the host immune response. We are on track to report preliminary data from this portion of the trial next week at ASLD. The totality of these data support our plans to advance Mduceran into a Phase IIb clinical trial as a cornerstone in a potential HPV functional cure treatment regimen. Now we'd like to move on to AB101, oral small molecule PD-L1 checkpoint inhibitor. We believe that the immune checkpoint pathway plays an important role in HPV-specific immune tolerance and in T cell activation, and the addition of a checkpoint inhibitor in combination with imduceran could potentially further enhance HPV-specific immune responses. We remain excited about the potential of AB101 in treating HPV. AB101 is liver-centric and in preclinical studies had typical small molecule pharmacokinetics. likely providing a much shorter duration of effect than long-acting antibodies. AB101 was designed with the goal of minimizing systemic exposure and reducing the chance of immune-related adverse events that are often seen with checkpoint antibodies. AB101 is currently in a phase 1A, 1B clinical trial that consists of three parts, starting with single and multiple ascending doses in healthy subjects and culminating with multiple doses in patients with chronic HPV. Last quarter, we reported data from the part one single ascending dose portion of the trial showing that AB101 was generally well tolerated with evidence of dose-dependent receptor occupancy. In the 25 milligram single dose cohort, all five evaluable subjects showed evidence of PD-L1 receptor occupancy between 50 and 100%, indicating that AB101 is interacting with its intended target. Today, we reported data from phase two of this trial where part, excuse me, part two of this trial where we have so far enrolled two sequential cohorts of 10 healthy subjects. Each cohort received 10 or 25 milligrams of AB101 or placebo daily for seven days. Multiple ascending doses of AB101 were generally well tolerated with evidence of dose-dependent receptor occupancy. In the 25 milligram cohort, all subjects showed evidence of receptor occupancy with seven of the eight subjects demonstrating receptor occupancy greater than 70% during the seven-day dosing period. With a favorable safety profile to date and evidence of receptor occupancy, we have now moved into part three, the global portion of this clinical trial, which evaluates 28 days of repeat dosing in AB101 in patients with chronic HPV. We expect to report preliminary data from HPV patients dosed with AB101 in the first half of next year. Finally, I have two brief updates on the litigation progress with Moderna and Pfizer-BioNTech around our LNP intellectual property. In the Moderna case, the trial date is now scheduled for September 24th, 2025, which is of course subject to the court's availability. In the Pfizer-BioNTech lawsuit, the date for the claim construction hearing, also known as the Markman hearing, has been set for December 18th, 2024. I'll now turn the call over to Dave Hastings for a brief financial update.