Imdusiran

Strong financial position with cash, cash equivalents and marketable securities of $91.5M as of December 2025 $2.25B Moderna global settlement for infringement of lipid nanoparticle (LNP) delivery technology represents significant outcome for Arbutus and Genevant Two additional patients from Phase 2a clinical trials of imdusiran achieve functional cure Milestone payment received under Alnylam LNP license for product candidate to treat hepatocellular carcinoma (HCC) WARMINSTER, Pa., March 23, 2026 (GLOBE NEWSWIRE) -- Arbutus Biopharma Corporation (Nasdaq: ABUS) (“Arbutus” or the “Company”), a clinical-stage biopharmaceutical company focused on infectious disease, today reported fourth quarter and year end 2025 financial results and provided a corporate update. “We delivered another strong quarter, maintaining a disciplined approach to capital allocation and a continued focus on maximizing our cash runway,” said Lindsay Androski, President and CEO of Arbutus. “I am thrilled to announce that two additional patients from our Phase 2a trials of imdusiran have achieved functional cure in chronic hepatitis B (“cHBV”), and am pleased with our team’s continuing progress on our cHBV programs.” LNP Litigation On March 3, 2026, Arbutus, along with its exclusive licensee, Genevant Sciences (“Genevant”), entered into a settlement agreement to resolve all global patent infringement litigation and patent revocation proceedings involving Moderna. As part of the settlement, Moderna will pay Arbutus and Genevant $950 million upfront in July 2026 (“Noncontingent Settlement Payment”) and an additional $1.3 billion contingent upon an appellate ruling that 28 U.S.C. §1498 (“Section 1498”) does not bar Arbutus’ and Genevant’s claims against Moderna for patent infringement, except as to doses characterized by the district court as having gone to U.S. government employees. In asserting that defense, Moderna argued that Section 1498 applies such that U.S. taxpayers should assume liability for its infringement of Arbutus’ and Genevant’s patents for sales made under one of its government contracts. Moderna has also consented to entry of a judgment of infringement and of no invalidity of four Arbutus/Genevant patents. For more information about the terms and conditions of the settlement with Moderna, including the contingent payment, please refer to Arbutus’ Annual Report on Form 10-K filed with the SEC on March 20, 2026. Under the Company’s license with Genevant, the Company is entitled to receive, after deduction of litigation costs, 20% of the Noncontingent Settlement Payment. In addition, the Company owns approximately 16% of the outstanding common equity of Genevant.Arbutus continues to consult closely with and support Genevant to protect and defend Arbutus’ intellectual property, which is the subject of an on-going lawsuit against Pfizer/BioNTech. The Company, together with Genevant, is seeking fair compensation for use of Arbutus’ patented lipid nanoparticle (“LNP”) technology that was developed with great effort and at a great expense, and without which Pfizer/BioNTech’s COVID-19 vaccines would not have been successful. The claim construction hearing for the lawsuit against Pfizer/BioNTech occurred in December 2024, and the court issued a claim construction ruling in September 2025, which construed the disputed claim terms in a manner the Company generally considers to be favorable. The parties are awaiting further scheduling in the litigation. Corporate Updates Two additional patients from the Company’s Phase 2a clinical trials of imdusiran achieved functional cure, making a total of 10 patients to date that have achieved functional cure during Phase 2a clinical trials and long-term follow-up. Two of these functionally cured patients seroreverted during long-term follow-up, but remain virally suppressed and off nucleos(t)ide analogue (“NA”) therapy.In December 2025, the Company recognized revenue of $0.5 million following the achievement of a contractual milestone related to Alnylam’s use of the Company’s proprietary LNP technology in an additional product candidate to treat hepatocellular carcinoma (HCC), underscoring the important role the Company’s LNP technology plays in the delivery of nucleic acids to the body. Payment was received in January 2026.In connection with payments the Company expects to receive under the Moderna settlement, the Company is currently evaluating a return of capital to its shareholders in the third quarter of calendar year 2026, following the receipt of its portion of the noncontingent lump sum payment from Moderna. Financial Results Cash, Cash Equivalents and Investments As of December 31, 2025, the Company had cash, cash equivalents and investments in marketable securities of $91.5 million compared to $122.6 million as of December 31, 2024. During the year ended December 31, 2025, the Company used $39.6 million in operating activities, which included one-time payments related to its restructuring efforts. This was partially offset by $5.5 million of proceeds from the exercise of stock options. Revenue Total revenue was $14.1 million for the year ended December 31, 2025, compared to $6.2 million for the same period in 2024. The increase of $7.9 million was due to the recognition of all previously-deferred revenue as a result of the conclusion of the Company’s strategic partnership with Qilu Pharmaceutical, partially offset by a decrease in license royalty revenues due to a decline in Alnylam’s sales of ONPATTRO. Operating Expenses Research and development expenses were $25.2 million for the year ended December 31, 2025, compared to $54.0 million for the same period in 2024. The decrease of $28.8 million was due primarily to cost savings from the Company’s decisions to streamline the organization to focus its efforts on advancing the clinical development of imdusiran and AB-101, which included ceasing all discovery efforts, discontinuing its IM-PROVE III clinical trial, and right-sizing the Company’s workforce. General and administrative expenses were $15.9 million for the year ended December 31, 2025, compared to $22.1 million for the same period in 2024. This decrease was due primarily to cost-cutting efforts by the Company, which drove reductions in employee compensation-related expenses and legal fees. Restructuring costs for the year ended December 31, 2025 were $12.9 million, and all remaining restructuring-related payments are expected to be made by the first quarter of 2026. Net Loss For the year ended December 31, 2025, the Company’s net loss was $33.5 million, or a loss of $0.17 per basic and diluted common share, as compared to a net loss of $69.9 million, or a loss of $0.38 per basic and diluted common share, for the quarter ended December 31, 2024. Outstanding Shares As of December 31, 2025, the Company had 192.5 million common shares issued and outstanding, as well as 14.0 million stock options and unvested restricted stock units outstanding. UNAUDITED CONDENSED CONSOLIDATED STATEMENTS OF INCOME AND LOSS(in thousands, except share and per share data) Year ended December 31, 2025 2024 Revenue Collaborations and licenses$12,601 $3,919 Non-cash royalty revenue 1,482 2,252 Total revenue 14,083 6,171 Operating expenses Research and development 25,241 54,037 General and administrative 15,893 22,108 Change in fair value of contingent consideration (1,830) 2,625 Restructuring costs 12,939 3,720 Total operating expenses 52,243 82,490 Loss from operations (38,160) (76,319)Other income Interest income 4,068 6,585 Gain on sale of property and equipment 674 — Interest expense (97) (137)Foreign exchange gain / (loss) 14 (49)Total other income 4,659 6,399 Net loss$(33,501) $(69,920)Net loss per common share Basic and diluted$(0.17) $(0.38)Weighted average number of common shares Basic and diluted 191,599,600 185,608,874 UNAUDITED CONDENSED CONSOLIDATED BALANCE SHEETS(in thousands) December 31, 2025 December 31, 2024Cash, cash equivalents and marketable securities, current$91,471 $122,623Accounts receivable and other current assets 2,985 4,693Total current assets 94,456 127,316Property and equipment, net of accumulated depreciation and impairment 32 3,309Right of use asset — 1,048Other non-current assets 130 34Total assets$94,618 $131,707 Accounts payable and accrued liabilities$5,459 $7,564Deferred license revenue, current — 7,571Lease liability, current 547 483Total current liabilities 6,006 15,618Liability related to sale of future royalties 3,442 4,829Deferred license revenue, non-current — 2,863Contingent consideration 8,395 10,225Lease liability, non-current 199 806Total stockholders' equity 76,576 97,366Total liabilities and stockholders' equity$94,618 $131,707 UNAUDITED CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS(in thousands) Year ended December 31, 2025 2024 Net loss$(33,501) $(69,920)Non-cash items 3,887 7,899 Change in deferred license revenue (10,434) (1,357)Other changes in working capital 411 (1,472)Net cash used in operating activities (39,637) (64,850)Net cash provided by investing activities 15,580 22,948 Issuance of common shares pursuant to the Open Market Sale Agreement — 44,123 Cash provided by other financing activities 5,721 7,873 Net cash provided by financing activities 5,721 51,996 Effect of foreign exchange rate changes on cash and cash equivalents 14 (49)(Decrease) / increase in cash and cash equivalents (18,322) 10,045 Cash and cash equivalents, beginning of period 36,330 26,285 Cash and cash equivalents, end of period 18,008 36,330 Investments in marketable securities 73,463 86,293 Cash, cash equivalents and investments, end of period$91,471 $122,623 About Imdusiran (AB-729)   Imdusiran is an RNAi therapeutic specifically designed to reduce all hepatitis B viral proteins and antigens, including hepatitis B surface antigen (“HBsAg”), which is thought to be a key prerequisite to enable reawakening of a patient’s immune system to control the virus. Imdusiran targets hepatocytes using Arbutus’ novel covalently conjugated N-Acetylgalactosamine (“GalNAc”) delivery technology enabling subcutaneous delivery. In Arbutus’ Phase 2a clinical trials, eight patients with cHBV achieved functional cure following treatment with imdusiran and NA therapy in combination with either pegylated interferon alfa-2a or low dose nivolumab plus an immunotherapeutic, with six out of the eight patients continuing to sustain functional cure for over two years. An additional 41 patients across the Company’s Phase 2a clinical trials were able to remain off NA therapy for at least 48 weeks during their Phase 2a clinical trials following treatment with imdusiran. Two additional patients who discontinued NA therapy in their Phase 2a clinical trials have now achieved functional cure during their participation in long-term follow-up. Functional cure is defined as sustained HBsAg seroclearance and hepatitis B virus deoxyribonucleic acid (“HBV DNA”) less than the lower limit of quantification after 24 weeks off treatment, with or without anti-hepatitis B surface antibodies. Clinical data generated thus far has shown imdusiran to be generally safe and well-tolerated, while also providing meaningful reductions in HBsAg and HBV DNA. About HBV   Hepatitis B is a potentially life-threatening liver infection caused by hepatitis B virus (“HBV”). HBV can cause chronic infection which leads to a higher risk of death from cirrhosis and liver cancer. cHBV infection represents a significant unmet medical need. The World Health Organization estimates that over 250 million people worldwide suffer from cHBV infection, while other estimates indicate that approximately 2 million people in the United States suffer from cHBV infection. Approximately 1.1 million people die every year from complications related to cHBV infection despite the availability of effective vaccines and current treatment options. About Arbutus   Arbutus Biopharma Corporation (Nasdaq: ABUS) is a clinical-stage biopharmaceutical company focused on infectious disease. The Company is currently developing imdusiran (AB-729) and an oral PD-L1 inhibitor (AB-101) for the treatment of cHBV infection. The Company is also consulting closely with and supporting its exclusive licensee, Genevant Sciences, to protect and defend its intellectual property, which is the subject of on-going lawsuits against Moderna and Pfizer/BioNTech for use of Arbutus’ patented LNP technology in their COVID-19 vaccines. For more information, visit www.arbutusbio.com. Forward-Looking Statements and Information This press release contains forward-looking statements within the meaning of the Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, and forward-looking information within the meaning of Canadian securities laws (collectively, forward-looking statements). Forward-looking statements in this press release include statements about: the potential to lead to a functional cure for HBV and/or the discontinuation of HBV therapies after treatment with Arbutus’ product candidates; the durability of clinical benefits from Arbutus’ product candidates; the potential for Arbutus’ product candidates to achieve success in clinical trials; Arbutus’ pipeline and development plans for its cHBV programs; Arbutus’ plans with respect to ongoing patent litigation matters, including the expected timing thereof and the settlement of the Moderna litigation; and Arbutus’ evaluation of a potential return of capital to its shareholders. With respect to the forward-looking statements contained in this press release, Arbutus has made numerous assumptions regarding, among other things: the effectiveness and timeliness of clinical trials, and the usefulness of the data; the continued demand for Arbutus’ assets; and the stability of economic and market conditions. While Arbutus considers these assumptions to be reasonable, these assumptions are inherently subject to significant business, economic, competitive, market and social uncertainties and contingencies. Additionally, there are known and unknown risk factors which could cause Arbutus’ actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements contained herein. Known risk factors include, among others: ongoing and anticipated clinical trials may be more costly or take longer to complete than anticipated, and may never be initiated or completed, or may not generate results that warrant future development of the tested product candidate; Arbutus may elect to change its strategy regarding its product candidates and clinical development activities; Arbutus may not receive the necessary regulatory approvals for the clinical development of Arbutus’ product candidates; uncertainties associated with litigation generally and patent litigation specifically; economic and market conditions may worsen; market shifts may require a change in strategic focus; Arbutus’ workforce reduction and plans to reduce its net cash burn may not materially extend the cash runway and may create a distraction or uncertainty that may adversely affect its operating results, business, or investor perceptions; and risks related to the sufficiency of Arbutus’ cash resources for its foreseeable and unforeseeable operating expenses and capital expenditures. A more complete discussion of the risks and uncertainties facing Arbutus appears in Arbutus’ Annual Report on Form 10-K, Arbutus’ Quarterly Reports on Form 10-Q and Arbutus’ continuous and periodic disclosure filings, which are available at www.sedar.com and at www.sec.gov. All forward-looking statements herein are qualified in their entirety by this cautionary statement, and Arbutus disclaims any obligation to revise or update any such forward-looking statements or to publicly announce the result of any revisions to any of the forward-looking statements contained herein to reflect future results, events or developments, except as required by law. Arbutus Biopharma Corporation / ir@arbutusbio.com

乙肝并不是一个缺药的疾病，但始终缺一种能让多数患者真正结束治疗的方案。 过去二十多年，核苷（酸）类似物已经显著改写了慢性乙肝的自然病程。对多数规范治疗患者而言，HBV DNA可以被长期压低，肝炎活动得到控制，肝硬化和肝癌风险随之下降。问题在于，这套治疗更接近“长期管理”，而不是“感染终止”。很多患者一旦开始治疗，往往意味着长期维持；停药之后，病毒学和临床反弹仍是现实风险。EASL 2025指南仍将高屏障核苷（酸）类似物和PEG-IFN作为当前慢性HBV感染的主要治疗路径，而GSK在日本申报新闻稿中也再次强调，现有标准治疗下功能性治愈率通常只有约1%。 也正因此，乙肝创新药研发近年的重心，已经从“进一步压低HBV DNA”转向“功能性治愈”。GSK的Bepirovirsen受到关注，不只是因为它在2026年2月于日本被受理上市申请，更因为它所对应的，是乙肝治疗逻辑一次较为明确的转向：治疗重点从长期抑制复制，转向更直接地处理病毒转录本和表面抗原负荷。GSK披露，Bepirovirsen是其全球首个监管申报，申报依据来自B-Well 1和B-Well 2两项III期研究达到主要终点。一、HBV持续感染的分子基础 HBV是一个部分双链DNA病毒，但其复制方式带有明显的逆转录特征。病毒经NTCP受体介导进入肝细胞后，病毒衣壳释放，携带的松弛环状DNA（rcDNA）进入细胞核，并被修复为共价闭合环状DNA，也就是cccDNA。cccDNA以微小染色体样结构存在于细胞核内，成为后续病毒转录的核心模板。 此后，宿主RNA polymerase II以cccDNA为模板，转录出前基因组RNA（pgRNA）以及多种亚基因组mRNA。前基因组RNA既是后续逆转录生成新病毒DNA的模板，也编码核心蛋白和病毒聚合酶；亚基因组mRNA则翻译出表面蛋白、HBx以及前C/C相关蛋白。随后，核心蛋白、聚合酶与pgRNA重新装配成核衣壳，在核衣壳内部完成逆转录，生成新的部分双链DNA。新形成的核衣壳一部分被包膜后分泌出胞，形成新的病毒颗粒；另一部分则回流细胞核，补充cccDNA库。也就是说，外周HBV DNA下降，并不自动等同于核内cccDNA被清除；只要cccDNA仍在，病毒就仍保留重新转录、重新复制和重新输出病毒蛋白的能力。 在乙肝讨论中，HBsAg、HBV DNA和HBV RNA常被同时提到，但三者并不是一回事。HBsAg是乙型肝炎表面抗原，可以理解为体内持续病毒抗原负荷最直观的血清学输出之一；HBV DNA更接近“复制产物”，通常反映血液中可检测到的病毒基因组水平；HBV RNA则位于两者之间，更接近“病毒转录活动”的层面，是cccDNA转录后的信息中介，也是后续蛋白翻译和逆转录复制的上游。核苷（酸）类似物最擅长压低HBV DNA，但未必同步降低HBsAg；而ASO和siRNA这类核酸药物则更直接作用于HBV RNA层面。二、乙肝难治的三层障碍 乙肝之所以难以走向治愈，并不是单一问题，而是至少三层障碍叠加。 第一层是cccDNA持续存在。现有标准治疗，尤其是核苷（酸）类似物，主要作用于逆转录和DNA复制阶段，能够显著抑制血液中的HBV DNA，但通常无法直接清除核内cccDNA。也正因此，即使外周病毒学指标长期受控，只要停药，残留cccDNA仍可能重新恢复转录，带来反弹。 第二层复杂性在于，HBsAg并不完全来源于cccDNA转录。近年的研究逐渐发现，在长期核苷（酸）类似物（NA）治疗背景下，整合到宿主染色体中的HBV DNA同样可以持续表达表面抗原，甚至可能成为HBsAg的重要来源之一。由于NA主要抑制病毒复制，对整合HBV DNA的转录表达影响有限，因此即便HBV DNA已经被压到很低水平，HBsAg仍可能长期维持在较高水平。 第三层是免疫控制难以恢复。HBsAg长期高负荷表达被认为与宿主抗HBV免疫应答受损密切相关，尤其会影响HBV特异性T细胞功能。换言之，乙肝的“难治”并不只是病毒复制顽固，而是核内模板、抗原持续表达和免疫失衡同时存在。 三、现有治疗手段 核苷（酸）类似物仍是一线基础治疗，包括恩替卡韦、替诺福韦酯和丙酚替诺福韦等。它们的主要作用位点是逆转录复制阶段，能够强力抑制HBV DNA合成，降低病毒血症和肝脏炎症活动。其边界在于，对cccDNA清除作用有限，对HBsAg清除帮助也有限，因此很多患者需要长期乃至终身维持。 PEG-IFN更接近免疫调节路线。它并不主要依赖直接阻断病毒复制，而是试图通过调动宿主免疫，帮助患者获得更深层应答。理论上，它比NA更接近有限疗程和HBsAg清除目标；但耐受性、患者选择和真实世界实施难度始终是限制。 在这个基础上，小核酸药物的重要性开始上升。ASO和siRNA的具体药理机制不同，但共同瞄准的是HBV RNA这一层。由于HBV蛋白表达、包括HBsAg的持续输出依赖病毒RNA转录本，这类药物实际上是在截断下游蛋白表达链条。对乙肝而言，这比单纯压制DNA复制更接近抗原负荷问题，也更接近功能性治愈的瓶颈。四、Bepirovirsen的作用机理与研发位置4.1作用位点：靶向HBV RNA而非直接清除cccDNA Bepirovirsen属于反义寡核苷酸，也就是ASO。它的作用逻辑不是直接清除cccDNA，而是更靠下游：靶向HBV RNA本身。 根据Nature Medicine早期研究和GSK公开资料，Bepirovirsen靶向所有HBV mRNA和前基因组RNA。ASO与目标RNA结合后，可通过RNase H介导RNA降解。其结果是，HBV转录本减少，依赖这些RNA翻译出来的病毒蛋白也随之下降，包括HBsAg；同时，pgRNA减少也会削弱后续逆转录和病毒复制。它打击的并不是核内模板本身，而是模板转录后的“信息流”及由此产生的蛋白输出。 这一路径在乙肝中的意义非常直接。只要病毒仍在持续输出HBsAg，宿主免疫就很难真正恢复控制；而如果能持续降低HBsAg，理论上就可能为免疫重建创造条件。也正因为如此，Bepirovirsen在乙肝中的价值，不在于替代所有现有治疗，而在于把治疗重心推进到功能性治愈真正相关的层级。4.2同类核酸药物版图 从临床推进速度看，Bepirovirsen目前是慢乙肝核酸药物中最接近注册突破的项目；但从研发方法论看，真正值得重视的不是单个品种领先，而是“以HBV RNA和HBsAg为中心的抗原降低策略”正在逐步成为乙肝功能性治愈研发的主轴。 五、临床研究证据 Bepirovirsen的早期关键证据来自2021年发表于Nature Medicine的随机II期研究。该研究显示，Bepirovirsen能够降低慢性HBV感染患者的HBsAg、HBV DNA和HBV RNA。安全性方面，常见不良事件多为轻中度，最常见的是注射部位反应；同时观察到ALT升高，部分为较明显的ALT flare，多数为短暂且自限。这种ALT变化可能与药理活性及感染肝细胞清除有关，但这一解释仍需在更大样本中继续验证。 2022年的B-Clear IIb研究进一步提高了这一药物的临床确定性。GSK公开资料显示，在24周、每周300 mg并带loading dose的方案下，正在接受NA治疗的人群中，9%达到主要终点；未接受NA治疗的人群中，这一比例为10%。在低基线HBsAg亚组中，这一比例分别为16%和25%。这些结果提示，有限疗程ASO单药已可使部分患者达到持续HBsAg和HBV DNA丢失相关终点。 III期阶段，GSK公布B-Well 1和B-Well 2共纳入1800多名患者，覆盖29个国家，Bepirovirsen联合标准治疗的功能性治愈率显著优于单纯标准治疗；公司同时指出，较低基线HBsAg患者获益更为明显。由于完整III期论文及全部分层结果尚未完全公开，现阶段更合适的表述仍是：注册层面的积极信号已经成立，但疗效细节与适用边界仍需等待更完整披露。六、临床价值与研发边界 Bepirovirsen最重要的临床价值，不在于比NA更擅长压制HBV DNA，而在于它更直接作用于HBV RNA和HBsAg。这一层恰好是乙肝功能性治愈迟迟难以突破的关键障碍之一。 第二个价值是有限疗程潜力。GSK在III期新闻稿中将其定位为潜在首个“6个月有限疗程”慢乙肝治疗方案之一。与长期口服NA相比，它的差异化不在单次给药便利性，而在整体疗程可能更短、停药目标更明确。需要强调的是，Bepirovirsen不是口服药，早期研究采用的是皮下注射方案。 但边界同样清楚。首先，并非所有患者都会取得较深应答，低基线HBsAg患者目前看起来更容易获益。其次，ALT flare在临床实践中仍需要严肃对待。再次，它主要作用于RNA与抗原输出层面，而cccDNA持续存在、整合DNA来源HBsAg表达以及宿主免疫失衡等问题，并不会因此自动消失。功能性治愈也不应被等同为彻底清除全部病毒学痕迹。七、结语 Bepirovirsen的意义，不止于一个乙肝ASO进入日本审评。 它更值得关注的地方在于，乙肝治疗的关注点正在从“把复制压得更低”转向“如何降低抗原负荷，并让患者有机会在有限疗程后结束治疗”。这条路还远没有走到终点。cccDNA、整合DNA来源HBsAg、免疫控制失衡，仍然是功能性治愈最核心的障碍。 但至少到今天，Bepirovirsen已经把这件事往前推了一步。它让乙肝功能性治愈不再只是一个高度抽象的研究目标，而开始进入可以被III期验证、被监管审评的现实阶段。八、参考文献 GSK. Bepirovirsen accepted for regulatory review in Japan as a potential first-in-class treatment for chronic hepatitis B. 2026-02-26. GSK. GSK announces positive results from B-Well 1 and B-Well 2 phase III trials for bepirovirsen. 2026-01-07. Yuen M F, Heo J, Jang J W, et al. Safety, tolerability and antiviral activity of the antisense oligonucleotide bepirovirsen in patients with chronic hepatitis B: a phase 2 randomized controlled trial[J]. Nature medicine, 2021, 27(10): 1725-1734. European Association for the Study of the Liver. EASL Clinical Practice Guidelines on the management of hepatitis B virus infection[J]. Journal of hepatology, 2025, 83(2): 502-583. Zoulim F, Chen P J, Dandri M, et al. Hepatitis B virus DNA integration: Implications for diagnostics, therapy, and outcome[J]. Journal of Hepatology, 2024, 81(6): 1087-1099. Elebsiran相关II期结果与联合PEG-IFN研究。 JNJ-3989相关II期研究。 Imdusiran（AB-729）相关II期与长期随访研究。 立即扫码加入药事纵横交流群