End-of-treatment data from two Phase 2a combination clinical trials with imdusiran to be presented at the EASL Congress in June 2024 Preliminary data from the single-dose portion of the AB-101-001 clinical trial show that AB-101 was generally well-tolerated and bound to the receptor target in healthy subjects Court provides claim construction ruling in ongoing patent infringement lawsuit against Moderna; Court date scheduled for April 21, 2025 Strong financial position – expected cash runway extended through the second quarter of 2026 Conference Call and Webcast Today at 8:45 AM ET WARMINSTER, Pa., May 02, 2024 (GLOBE NEWSWIRE) -- Arbutus Biopharma Corporation (NASDAQ:ABUS) ("Arbutus" or the "Company"), a clinical-stage biopharmaceutical company leveraging its extensive virology expertise to develop a functional cure for people with chronic hepatitis B virus (cHBV) infection, today reports first quarter 2024 financial results and provides a corporate update. "We continued to make progress in the first quarter of 2024 in advancing our pipeline of HBV assets," said Michael J. McElhaugh, Interim President and Chief Executive Officer of Arbutus Biopharma. "Along with imdusiran, which we see as a potential cornerstone therapeutic, we believe an immune modulator also plays an important role in the treatment regimen to functionally cure cHBV. In pursuit of this goal, we have initiated our third Phase 2a trial combining imdusiran with an immune modulator and are reporting the first part of the Phase 1a/1b trial with AB-101, our oral proprietary PD-L1 checkpoint inhibitor. The end-of-treatment data from our two ongoing Phase 2a combination trials with imdusiran and other immune modulators will be presented at the EASL conference upcoming in June. With an expected cash runway now through the second quarter of 2026, we are well funded to move our existing clinical trials forward to achieve meaningful data and advance into a later stage clinical trial." Clinical Development Update Imdusiran (AB-729, RNAi Therapeutic)      AB-729-201 is a Phase 2a clinical trial that is evaluating the safety, tolerability and antiviral activity of the combination of imdusiran, nucleos(t)ide analogue (NA) therapy and pegylated interferon alfa-2a (IFN) in patients with cHBV. Preliminary data presented at the EASL Congress in June 2023 suggest that the addition of IFN to imdusiran was generally well-tolerated and appears to result in continued HBsAg declines in some patients. End-of-treatment data from this trial will be shared at the upcoming EASL Congress in June. AB-729-202 is a Phase 2a clinical trial that is evaluating the safety and immunogenicity of imdusiran, NA therapy and Barinthus Bio's VTP-300, an HBV antigen-specific immunotherapy.  Preliminary data presented at AASLD – The Liver Meeting in November 2023 showed that the combination of imdusiran and VTP-300 provided a meaningful reduction of HBsAg levels that are maintained well below baseline. End-of-treatment data from this portion of the trial will be shared at the upcoming EASL Congress in June. AB-729-202 was amended to include an additional cohort of 20 patients who will receive imdusiran plus NA therapy for 24 weeks followed by VTP-300 plus up to two low doses of nivolumab, an approved anti-PD-1 monoclonal antibody. Preliminary end-of-treatment data from this additional cohort are expected in the second half of 2024.     AB-729-203 is a Phase 2a clinical trial evaluating the safety, tolerability and antiviral activity of imdusiran and NA therapy in combination with intermittent low doses of durvalumab, an approved anti-PD-L1 monoclonal antibody. Patients are being screened in this clinical trial. The clinical trial is designed to enroll 30 patients in three separate cohorts. All patients will receive 60mg of imdusiran every 8 weeks for 48 weeks and 2 doses of durvalumab given via IV infusion at pre-specified times during the imdusiran treatment period that will differ by cohort.   After completion of treatment, all patients will be assessed for NA discontinuation and followed for at least 24 to 48 weeks.   AB-101 (Oral PD-L1 Inhibitor)      AB-101-001 is a Phase 1a/1b double-blind, randomized, placebo-controlled clinical trial designed to investigate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single- and multiple-ascending oral doses of AB-101 for up to 28 days in healthy subjects and patients with cHBV. Part 1 of the clinical trial has enrolled four sequential cohorts of eight healthy subjects each (6 active:2 placebo) to date, each receiving a single dose of AB-101 at increasing dose levels up to 25mg or placebo. In this trial, AB-101 was generally well-tolerated with evidence of dose-dependent receptor occupancy. In the 25mg cohort, all five evaluable subjects showed evidence of receptor occupancy between 50-100%. Arbutus has moved into Part 2 of this clinical trial which evaluates multiple-ascending doses of AB-101 in healthy subjects and expects to report preliminary data in the second half of this year. Corporate Updates In a separate press release issued today, Arbutus announced that Michael J. Sofia, PhD will be retiring as Chief Scientific Officer at the end of 2024. Dr. Sofia is a co-founder of Arbutus and a globally recognized, Lasker award-winning antiviral drug discovery and development scientist. The following abstracts were accepted for presentation at the EASL Congress 2024: Abstract Title: Imdusiran (AB-729) administered every 8 weeks in combination with 24 weeks of pegylated interferon alfa-2a in virally suppressed, HBeAg-negative subjects with chronic HBV infection leads to HBsAg loss in some subjects at end of IFN treatment. Authors: Man-Fung Yuen, Jeong Heo, Ronald G Nahass, Grace Lai-Hung Wong, Tatiana Burda, Kalyan Ram Bhamidimarri, Tsung-Hui Hu, Tuan T Nguyen, Young-Suk Lim, Chi-Yi Chen, Stuart C Gordon, Jacinta Holmes, Wan-Long Chuang, Anita Kohli, Naim Alkhouri, Kevin Gray, Emily P. Thi, Elina Medvedeva, Timothy Eley, Sharie C Ganchua, Christina Iott, Elizabeth Eill, Christine L. Espiritu, Mark Anderson, Tiffany Fortney, Gavin Cloherty, Karen D Sims Abstract Title: Imdusiran (AB-729) administered every 8 weeks for 24 weeks followed by the immunotherapeutic VTP-300 maintains lower HBV surface antigen levels in NA-suppressed CHB subjects than 24 weeks of imdusiran alone. Authors: Kosh Agarwal, Man-Fung Yuen, Stuart Roberts, Gin-Ho Lo, Chao-Wei Hsu, Wan-Long Chuang, Chi-Yi Chen, Pei-Yuan Su, Sam Galhenage, Sheng-Shun Yang, Emily P. Thi, Katie Anderson, Deana Antoniello, Elina Medvedeva, Timothy Eley, Tilly Varughese, Louise Bussey, Charlotte Davis, Antonella Vardeu, Christine L. Espiritu, Sharie C Ganchua, Christina Iott, Elizabeth Eill, Tom Evans, Karen D Sims LNP Litigation Update: With respect to the Moderna lawsuit, the claim construction hearing occurred on February 8, 2024. On April 3, 2024, the Court provided its claim construction ruling, in which it construed the disputed claim terms and agreed with Arbutus' position on most of the disputed claim terms. Fact discovery is on-going and next steps include expert reports and depositions. A trial date has been set for April 21, 2025, and is subject to change. The lawsuit against Pfizer/BioNTech is ongoing and a date for a claim construction hearing has not been set.   Arbutus continues to protect and defend its intellectual property, which is the subject of the on-going lawsuits against Moderna and Pfizer/BioNTech. The Company is seeking fair compensation for Moderna's and Pfizer/BioNTech's use of its patented LNP technology that was developed with great effort and at a great expense, without which Moderna and Pfizer/BioNTech's COVID-19 vaccines would not have been successful. Financial Results Cash, Cash Equivalents and Investments As of March 31, 2024, the Company had cash, cash equivalents and investments in marketable securities of $137.9 million compared to $132.3 million as of December 31, 2023. During the three months ended March 31, 2024, the Company used $19.3 million in operating activities, which was offset by $21.8 million of net proceeds from the issuance of common shares under its "at-the-market" offering program (ATM Program). During April 2024, the Company received an additional $22.4 million of net proceeds under its ATM Program. The Company expects its 2024 net cash burn to range from between $63 million to $67 million, excluding any proceeds received from its ATM Program.  The Company believes its cash, cash equivalents and investments in marketable securities including the additional net proceeds received under its ATM Program during April 2024, will be sufficient to fund its operations through the second quarter of 2026. Revenue Total revenue was $1.5 million for the three months ended March 31, 2024 compared to $6.7 million for the same period in 2023. The decrease of $5.2 million was due primarily to: i) a decrease in license revenue recognized related to the Company's progress towards the satisfaction of its performance obligations with respect to the licensing agreement with Qilu; and ii) a decrease in license royalty revenue from Alnylam due to lower sales of ONPATTRO in 2024 compared to 2023. Operating Expenses Research and development expenses were $15.4 million for the three months ended March 31, 2024 compared to $18.3 million for the same period in 2023. The decrease of $2.9 million was due primarily to the discontinuation of the Company's AB-161 and coronavirus programs in September 2023 as part of its efforts to focus its pipeline on its lead HBV product candidates, partially offset by an increase in clinical expenses for the Company's multiple imdusiran Phase 2a clinical trials. General and administrative expenses were $5.3 million for the three months ended March 31, 2024 compared to $5.6 million for the same period in 2023. The decrease of $0.3 million was due primarily to a decrease in non-cash stock-based compensation expenses. Net Loss For the three months ended March 31, 2024, the Company net loss was $17.9 million, or a loss of $0.10 per basic and diluted common share, as compared to a net loss of $16.3 million, or a loss of $0.10 per basic and diluted common share, for the three months ended March 31, 2023.   Outstanding Shares As of March 31, 2024, the Company had approximately 180.2 million common shares issued and outstanding. During April 2024, the Company issued an additional 7.8 million common shares under its ATM program. In addition, the Company had approximately 22.6 million stock options and unvested restricted stock units outstanding as of March 31, 2024. Roivant Sciences Ltd. owned approximately 20% of our outstanding common shares as of April 30, 2024. UNAUDITED CONDENSED CONSOLIDATED STATEMENTS OF LOSS (in thousands, except share and per share data)     Three Months Ended March 31,   2024   2023 Revenue       Collaborations and licenses $ 939     $ 5,509   Non-cash royalty revenue 593     1,178   Total revenue 1,532     6,687   Operating expenses       Research and development