ChAdOx1-HBV

Imdusiran data from IM-PROVE I and IM-PROVE II Phase 2a clinical trials to be presented at upcoming AASLD - The Liver Meeting 2024 Multiple-ascending doses of AB-101 in healthy subjects in the Phase 1a/1b clinical trial were generally safe and well-tolerated with evidence of receptor occupancy Now dosing cHBV patients with AB-101 in Part 3 of the Phase 1a/1b clinical trial Cash runway into the fourth quarter of 2026Conference Call and Webcast Today at 8:45 AM ET WARMINSTER, Pa., Nov. 06, 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 third quarter 2024 financial results and provides a corporate update. “We are making significant progress in advancing the development of imdusiran to bring hope to millions of cHBV patients globally,” said Michael J. McElhaugh, Interim President and Chief Executive Officer of Arbutus Biopharma. “In June, we shared promising data from our IM-PROVE I Phase 2a clinical trial, showing that some patients treated with imdusiran and interferon were trending towards a functional cure. We look forward to presenting follow-up data from this trial, as well as end-of-treatment data from patients that received nivolumab in addition to imdusiran and VTP-300 in our IM-PROVE II Phase 2a trial, at the upcoming AASLD meeting. Assuming continued positive data, and with a projected cash runway extending into the fourth quarter of 2026, we are well-positioned to advance imdusiran into a Phase 2b clinical trial as a cornerstone in a treatment regimen aimed at functionally curing cHBV.” Mr. McElhaugh continued, “Our proprietary oral PD-L1 checkpoint inhibitor, AB-101, is progressing well, as we continue to see dose-dependent receptor occupancy and have now advanced into dosing cHBV patients in our Phase 1a/1b clinical trial. We look forward to providing updates as this trial progresses.” Clinical Development Update Imdusiran (AB-729, RNAi Therapeutic) End-of-treatment data from the IM-PROVE I Phase 2a clinical trial evaluating the safety, tolerability and antiviral activity of the combination of imdusiran (4 or 6 doses over 24 or 48 weeks, respectively), nucleos(t)ide analogue (NA) therapy and a short course of pegylated interferon alfa-2a (IFN, 12 or 24 weeks) in patients with cHBV was presented at the EASL Congress in June. The data showed that 33.3% (n=4/12) of patients in Cohort A1 receiving 48 weeks (6 doses) of imdusiran combined with 24 weeks of IFN and NA therapy achieved HBsAg loss at the end-of-treatment that was maintained in 100% of these patients 24 weeks after completing imdusiran and IFN treatment. HBsAg loss was achieved and maintained in 67% of those patients with HBsAg less than 1000 IU/mL at baseline. A total of six patients from Cohort A1 (n=4) and Cohort A2 (n=2) seroconverted with HBsAg loss. At the time the data was reported, all six of those patients had stopped all therapy, with two of those patients reaching 12 weeks off all therapy with sustained HBsAg and HBV DNA loss. The combination of imdusiran and IFN in this clinical trial was generally safe and well-tolerated. The Company will present a late-breaker poster with additional follow-up data at the upcoming AASLD-The Liver Meeting 2024 later this month. End-of treatment data from the IM-PROVE II Phase 2a clinical trial evaluating the safety and immunogenicity of imdusiran, NA therapy and Barinthus Bio’s VTP-300, an HBV antigen-specific immunotherapy was presented at the EASL Congress in June. The data showed that the combination of imdusiran and VTP-300 was generally safe and well-tolerated. At 24-weeks post-end of treatment, statistical significance (p<0.05) was achieved in HBsAg levels between the VTP-300 arm (n=5) and placebo (n=6). IM-PROVE II includes an additional cohort of patients who received 4 doses of 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. The Company will present a late-breaker poster with preliminary end-of-treatment data from this additional cohort at the upcoming AASLD - The Liver Meeting 2024 in November. 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 in healthy subjects and patients with cHBV.Part 2 of this clinical trial has enrolled to date two sequential cohorts of ten healthy subjects each receiving 10 mg or 25 mg of AB-101 (n=8) or placebo (n=2) daily for 7 days. AB-101 was generally well-tolerated with evidence of dose-dependent receptor occupancy. In the 25 mg cohort, all subjects showed evidence of receptor occupancy, with seven of the eight subjects demonstrating receptor occupancy greater than 70% during the 7-day dosing period.Arbutus has moved into Part 3 of this clinical trial which evaluates repeat dosing of AB-101 for 28 days in patients with cHBV and expects to report preliminary data in the first half of next year. LNP Litigation Update Expert reports and expert depositions continue in the Moderna lawsuit. A trial date has been set for September 24, 2025, and is subject to the Court’s availability.The lawsuit against Pfizer/BioNTech is ongoing and a date for the claim construction hearing has been set for December 18, 2024.  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’s and Pfizer/BioNTech’s COVID-19 vaccines would not have been successful. Financial Results Cash, Cash Equivalents and Investments As of September 30, 2024, the Company had cash, cash equivalents and investments in marketable securities of $130.8 million compared to $132.3 million as of December 31, 2023. During the nine months ended September 30, 2024, the Company used $54.5 million in operating activities, which was partially offset by $44.1 million of net proceeds from the issuance of common shares under its “at-the-market” offering program (ATM Program) and $6.1 million of proceeds from the exercise of stock options. The Company did not issue any common shares under its ATM program in the third quarter of 2024. The Company expects its 2024 cash burn to range from $63 million to $67 million. With the organizational changes in the third quarter, the Company believes its cash, cash equivalents and investments in marketable securities will be sufficient to fund its operations into the fourth quarter of 2026. Revenue Total revenue was $1.3 million for the three months ended September 30, 2024 compared to $4.7 million for the same period in 2023. The decrease of $3.4 million was due primarily to: i) a decrease in license revenue recognized under the Company’s licensing agreement with Qilu Pharmaceutical; 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 $14.3 million for the three months ended September 30, 2024 compared to $20.2 million for the same period in 2023. The decrease of $5.9 million was due primarily to the discontinuation of the Company’s coronavirus and AB-161 programs in September 2023, along with related headcount reductions. General and administrative expenses were $4.5 million for the three months ended September 30, 2024 compared to $5.8 million for the same period in 2023. The decrease of $1.3 million was due primarily to decreased employee compensation and non-cash stock-based compensation expenses due to headcount reductions. The Company also incurred a $3.6 million one-time restructuring charge in the third quarter of 2024 related to its decision to cease all discovery efforts, discontinue its IM-PROVE III clinical trial, and reduce headcount to streamline the organization with a focus on advancing the clinical development of imdusiran and AB-101. Net Loss The Company’s net loss was $19.7 million for the three months ended September 30, 2024 and $20.1 million for the same period in 2023, with a loss per basic and diluted common share of $0.10 and $0.12, respectively. Outstanding Shares As of September 30, 2024, the Company had approximately 189.4 million common shares issued and outstanding. In addition, the Company had approximately 18.7 million stock options and unvested restricted stock units outstanding as of September 30, 2024. Roivant Sciences Ltd. owned approximately 21% of the Company’s outstanding common shares as of September 30, 2024. UNAUDITED CONDENSED CONSOLIDATED STATEMENTS OF LOSS(in thousands, except share and per share data) Three Months EndedSeptember 30, Nine Months EndedSeptember 30, 2024 2023 2024 2023 Revenue Collaborations and licenses$767 $3,935 $2,861 $13,329 Non-cash royalty revenue572 723 1,736 2,667 Total revenue1,339 4,658 4,597 15,996 Operating expenses Research and development14,273 20,169 45,227 56,136 General and administrative4,537 5,842 17,396 17,374 Change in fair value of contingent consideration344 205 735 (158)Restructuring3,625 - 3,625 - Total operating expenses22,779 26,216 66,983 73,352 Loss from operations(21,440) (21,558) (62,386) (57,356)Other income Interest income1,747 1,494 5,121 4,223 Interest expense(29) (46) (107) (415)Foreign exchange gain / (loss)5 6 (16) 11 Total other income1,723 1,454 4,998 3,819 Net loss$(19,717) $(20,104) $(57,388) $(53,537)Loss per share Basic and diluted$(0.10) $(0.12) $(0.31) $(0.32)Weighted average number of common shares Basic and diluted188,997,194 167,512,708 184,244,819 165,085,243 Comprehensive loss Unrealized gain on available-for-sale securities218 584 331 1,604 Comprehensive loss$(19,499) $(19,520) $(57,057) $(51,933) UNAUDITED CONDENSED CONSOLIDATED BALANCE SHEETS(in thousands) September 30, 2024 December 31, 2023Cash, cash equivalents and marketable securities, current$127,794 $126,003Accounts receivable and other current assets4,983 6,024Total current assets132,777 132,027Property and equipment, net of accumulated depreciation3,556 4,674Investments in marketable securities, non-current2,964 6,284Right of use asset1,144 1,416Total assets$140,441 $144,401Accounts payable and accrued liabilities$7,544 $10,271Deferred license revenue, current 10,911 11,791Lease liability, current468 425Total current liabilities18,923 22,487Liability related to sale of future royalties5,315 6,953Contingent consideration8,335 7,600Lease liability, non-current978 1,343Total stockholders’ equity106,890 106,018Total liabilities and stockholders’ equity$140,441 $144,401 UNAUDITED CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS(in thousands) Nine Months Ended September 30, 2024 2023Net loss$(57,388) $(53,537)Non-cash items5,453 4,613 Change in deferred license revenue(880) (10,349)Other changes in working capital(1,720) (9,371)Net cash used in operating activities(54,535) (68,644)Net cash provided by investing activities9,537 28,548 Issuance of common shares pursuant to the Open Market Sale Agreement44,124 26,000 Cash provided by other financing activities6,451 840 Net cash provided by financing activities50,575 26,840 Effect of foreign exchange rate changes on cash and cash equivalents(16) 11 Increase/(decrease) in cash and cash equivalents5,561 (13,245)Cash and cash equivalents, beginning of period26,285 30,776 Cash and cash equivalents, end of period31,846 17,531 Investments in marketable securities98,912 127,145 Cash, cash equivalents and marketable securities, end of period$130,758 $144,676 Conference Call and Webcast Today Arbutus will hold a conference call and webcast today, Wednesday, November 6, 2024, at 8:45 AM Eastern Time to provide a corporate update. To dial-in for the conference call by phone, please register using the following link: Registration Link. A live webcast of the conference call can be accessed through the Investors section of Arbutus' website at www.arbutusbio.com. An archived webcast will be available on the Arbutus website after the event. About Imdusiran (AB-729) Imdusiran is an RNA interference (RNAi) therapeutic specifically designed to reduce all HBV viral proteins and antigens including hepatitis B surface antigen, which is thought to be a key prerequisite to enable reawakening of a patient’s immune system to respond to the virus. Imdusiran targets hepatocytes using Arbutus’ novel covalently conjugated N-Acetylgalactosamine (GalNAc) delivery technology enabling subcutaneous delivery. Clinical data generated thus far has shown single and multiple doses of imdusiran to be generally safe and well-tolerated, while also providing meaningful reductions in hepatitis B surface antigen and hepatitis B DNA. Imdusiran is currently in multiple Phase 2a clinical trials.   About AB-101 AB-101 is our oral PD-L1 inhibitor candidate that we believe will allow for controlled checkpoint blockade while minimizing the systemic safety issues typically seen with checkpoint antibody therapies. Immune checkpoints such as PD-1/PD-L1 play an important role in the induction and maintenance of immune tolerance and in T-cell activation. Preclinical data generated thus far indicates that AB-101 mediates re-activation of exhausted HBV-specific T-cells from cHBV patients. We believe AB-101, when used in combination with other approved and investigational agents, could potentially lead to a functional cure in patients chronically infected with HBV. AB-101 is currently being evaluated in a Phase 1a/1b clinical trial. About HBV Hepatitis B is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV). HBV can cause chronic infection which leads to a higher risk of death from cirrhosis and liver cancer. Chronic HBV infection represents a significant unmet medical need. The World Health Organization estimates that over 250 million people worldwide suffer from chronic HBV infection, while other estimates indicate that approximately 2.4 million people in the United States suffer from chronic HBV infection. Approximately 820,000 people die every year from complications related to chronic HBV infection despite the availability of effective vaccines and current treatment options. About Arbutus Arbutus Biopharma Corporation (Nasdaq: ABUS) is a clinical-stage biopharmaceutical company leveraging its extensive virology expertise to develop novel therapeutics with distinct mechanisms of action, which can potentially be combined to provide a functional cure for patients with chronic hepatitis B virus (cHBV). We believe the key to success in developing a functional cure involves suppressing HBV DNA, reducing surface antigen, and boosting HBV-specific immune responses. Our pipeline of internally developed, proprietary compounds includes an RNAi therapeutic, imdusiran (AB-729), and an oral PD-L1 inhibitor, AB-101. Imdusiran has generated meaningful clinical data demonstrating an impact on both surface antigen reduction and reawakening of the HBV-specific immune response. Imdusiran is currently in two Phase 2a combination clinical trials. AB-101 is currently being evaluated in a Phase 1a/1b clinical trial. 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 our future development plans for our product candidates; the expected cost, timing and results of our clinical development plans and clinical trials with respect to our product candidates; our expectations with respect to the release of data from our clinical trials and the expected timing thereof; our expectations and goals for our collaborations with third parties and any potential benefits related thereto; our expectations regarding our organizational changes; the potential for our product candidates to achieve success in clinical trials; our expectations regarding our pending litigation matters; and our expected financial condition, including our anticipated net cash burn, the anticipated duration of cash runways and timing regarding needs for additional capital. 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 preclinical studies and clinical trials, and the usefulness of the data; the timeliness of regulatory approvals; 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, including uncertainties and contingencies related to patent litigation matters. 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: anticipated pre-clinical studies and 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’ products; economic and market conditions may worsen; Arbutus may not realize the anticipated benefits from the organizational changes; Arbutus may incur additional unexpected expenses in connection with the organizational changes; Arbutus may experience additional employee turnover as a result of the organizational changes; uncertainties associated with litigation generally and patent litigation specifically; and Arbutus and its collaborators may never realize the expected benefits of the collaborations; market shifts may require a change in strategic focus. 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. Contact Information Investors and Media Lisa M. CaperelliVice President, Investor RelationsPhone: 215-206-1822Email: lcaperelli@arbutusbio.com

▎药明康德内容团队编辑 Precision BioSciences近日宣布，其主打在研体内基因编辑疗法PBGENE-HBV的临床试验申请（CTA）已获得摩尔多瓦（Moldova）的监管单位批准。PBGENE-HBV旨在通过消除乙型肝炎病毒（HBV）的共价闭合环状DNA（cccDNA），同时灭活整合在肝细胞中的HBV DNA，以达到功能性治愈慢性乙型肝炎的目的。该公司已启动1期临床项目，并准备进行患者给药。Precision公司预计向全球监管单位提交更多的CTA和IND申请。根据新闻稿，PBGENE-HBV是进入临床阶段的首个靶向HBV的体内基因编辑疗法。 据统计，在2019年全球约有3亿人患有慢性乙型肝炎感染。乙肝病毒可造成严重的肝脏感染并造成慢性疾病，约15%至40%的HBV感染患者可能会发展为肝硬化、肝衰竭或肝癌，这些并发症是导致HBV相关死亡的主要原因。乙肝病毒会在患者肝细胞内的细胞核中产生一种独特、游离的cccDNA，这是病毒进行复制时的模板，因此病患cccDNA的含量成为乙肝病患治疗与病情评估的一项重要指标。乙肝病毒DNA还能整合到细胞的DNA中，并成为生成乙肝表面抗原（HBsAg）的源泉之一。目前的肝治疗方式可以限制乙肝病毒的复制，但无法清除这些乙肝病毒的基因成分，这是导致病毒慢性感染与复发的原因，患者通常需要终身用药，这是乙肝治疗时的关键挑战。 PBGENE-HBV是一款基于Precision公司专有ARCUS基因编辑平台所开发的体内基因编辑疗法，设计专门靶向HBV的基因。该疗法通过脂质纳米颗粒将编码ARCUS核酸酶的mRNA递送至肝脏。当在HBV感染的肝细胞中表达时，ARCUS核酸酶可特异性切割乙型肝炎病毒DNA中高度保守的序列，旨在消除cccDNA并灭活整合到细胞DNA中的HBV基因。 ARCUS平台最初由北卡罗来纳州的科学家们于2006年创立公司时开发。与常见的CRISPR/Cas9技术不同，ARCUS使用的是一种源自藻类的编辑酶。根据新闻稿，PBGENE-HBV是首款进入临床阶段的靶向HBV慢性感染根本原因——cccDNA的疗法。 ▲ARCUS基因编辑平台介绍（图片来源：Precision BioSciences公司官网） 目前，“功能性治愈”是乙肝治疗的一大重点方向。这指的是虽然我们无法彻底将病毒清除出人体外，但通过治疗，可以将其限制在非常低的水平，低到在血液中都无法被检测出的地步。研究人员们也期望在如此低的水平之下，乙肝患者依靠自身的免疫力就能控制病情，而无需继续接受药物的治疗。除了Precision公司，同样正在开发靶向HBV基因编辑疗法的还有Excision BioTherapeutics。该公司旗下的EBT-107是一种基于CRISPR的双引导RNA（gRNA）基因疗法，旨在有效抑制病毒并消除持续感染的根本来源，该公司计划在2026年第一季度启动临床1b期研究。 浩博医药（AusperBio）旗下靶向所有乙肝病毒RNA的反义寡核苷酸（ASO）疗法AHB–137目前正在临床2期试验当中受检视。在临床前研究中，它可以激发所有乙肝病毒RNA的降解，并且显著降低HBsAg水平。Virion Therapeutics也正在开发潜在“first-in-class”检查点修饰免疫疗法VRON-0200，该疗法利用腺病毒载体，在抗原呈递细胞中表达HBV抗原的同时，还表达调节免疫检查点信号通路的重组蛋白，旨在提供慢性HBV感染患者的功能性治愈。今年6月公布该疗法的首个人体临床试验早期数据显示，在至少有28天免疫学随访的9名患者中，大多数患者在接种后显示出增强的T细胞反应。VTP-300则是一种由Vaccitech公司开发、与疫苗作用机制非常类似的免疫疗法。利用Vaccitech的黑猩猩腺病毒载体（ChAdOx1）和改良牛痘安卡拉病毒（MVA）载体表达乙肝病毒抗原，激发抗HBV的免疫应答，有望为慢性乙肝患者带来功能性治愈，目前该疗法正在临床2期试验当中接受评估。 参考资料： [1] Precision BioSciences Receives First Approval of Clinical Trial Application to Initiate PBGENE-HBV First-In-Human Study for the Treatment of Chronic Hepatitis B. Retrieved October 24, 2024 from https://investor.precisionbiosciences.com/news-releases/news-release-details/precision-biosciences-receives-first-approval-clinical-trial [2] Exclusive: Moldova clears first gene editing study for HBV in humans. Retrieved October 24, 2024 from https://endpts.com/exclusive-moldova-clears-first-gene-editing-study-for-hbv-in-humans/ [3] Pipeline. Retrieved October 24, 2024 from https://www.excision.bio/technology/pipeline 本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权及其他合作需求，请联系wuxi_media@wuxiapptec.com。 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。