Arbutus Announces Decision to Discontinue AB-452 and to Pursue Development of a Next Generation HBV Specific Oral RNA-Destabilizer
Arbutus expects to announce AB-729 Preliminary Phase 1a/1b Data late Q12020
WARMINSTER, Pa., Feb. 10, 2020 (GLOBE NEWSWIRE) -- Arbutus Biopharma Corporation (Nasdaq: ABUS), announced today its decision to discontinue AB-452, its first generation orally available hepatitis B (HBV) specific RNA-destabilizer, and to continue research and development of a next generation oral HBV RNA-destabilizer. In October 2018, Arbutus announced its decision to delay the initiation of a planned 28-day Phase 1a/1b clinical trial for AB-452 in order to further evaluate the safety of the compound. This decision was based on findings in 90-day preclinical safety studies in two species. Since that time Arbutus has extensively reviewed and further characterized these preclinical findings, including repeating the 90-day safety studies.
Michael J. Sofia, Ph.D., Chief Scientific Officer of Arbutus, added, “After reviewing all the data from the preclinical studies, and in consultation with external regulatory and pre-clinical experts, we have decided to not move AB-452 forward. We continue to believe, however, that the HBV RNA destabilizer mechanism of action is very compelling and has the potential to lead to an oral therapy. We intend to vigorously pursue next generation compounds in this area.”
Arbutus also reiterated its earlier guidance for both AB-729 and AB-836. AB-729 is a subcutaneously delivered RNAi agent which has been shown in preclinical models to reduce viral antigens, including hepatitis B surface antigen (HBsAg) expression, and to inhibit HBV replication. In July 2019, the Company initiated a single and multiple dose Phase 1a/1b clinical trial for AB-729, designed to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of AB-729 in healthy volunteers and in subjects with chronic hepatitis B (CHB) infection. Preliminary safety data in single-dose cohorts of healthy subjects and safety and efficacy data in single-dose cohorts of subjects with CHB infection are expected late this quarter. For AB-836, Arbutus’ next generation capsid inhibitor, the Company expects to complete investigational new drug enabling studies by the end of the year.
The Company believes that this compound has the potential for increased efficacy and an enhanced resistance profile relative to its previous generation capsid inhibitor, AB-506.
William H. Collier, President and Chief Executive Officer of Arbutus, stated, “Arbutus remains committed to developing a range of medicines with differing mechanisms of action that can be used in combination for treatment of chronic HBV infection. The Company is on track to deliver on its key pipeline objectives for 2020; we look forward to announcing our preliminary safety and efficacy data for AB-729 later this quarter and to completing IND enabling studies for AB-836 by the end of the year.”
About Oral RNA-Destabilizers
Small molecule HBV RNA destabilizers are orally active agents that cause the destabilization and ultimate degradation of HBV RNAs. These agents result in the reduction of HBsAg, HBeAg, pgRNA, and core protein in both whole cell systems and animal models. They have the potential to selectively impact HBV versus other RNA or DNA viruses and demonstrate pangenotypic characteristics. HBV RNA destabilizers have demonstrated additive effects in combination with other mechanism of action anti-HBV agents.
About AB-729
AB-729 is a RNA interference (RNAi) therapeutic targeted to hepatocytes using Arbutus’ novel covalently conjugated N-acetylgalactosamine (GalNAc) delivery technology that enables subcutaneous delivery. AB-729 inhibits viral replication and reduces all HBV antigens, including hepatitis B surface antigen (HBsAg) in preclinical models. Reducing HBsAg is thought to be a key prerequisite to enable reawakening of a patient’s immune system to respond to the virus.
About AB-836
AB-836 is an oral HBV capsid inhibitor. HBV core protein assembles into a capsid structure, which is required for viral replication. The current standard-of-care therapy for HBV, primarily nucleoside analogues that work by inhibiting the viral polymerase, significantly reduce virus replication, but not completely. Capsid inhibitors inhibit replication by preventing the assembly of functional viral capsids. They also have been shown to inhibit the uncoating step of the viral life cycle thus reducing the formation of new covalently closed circular DNA (“cccDNA”), the viral reservoir which resides in the cell nucleus.作者: StephenW 时间: 2020-2-11 11:03
Arbutus总裁兼首席执行官William H. Collier表示：“ Arbutus仍致力于开发具有不同作用机制的多种药物，这些药物可联合用于治疗慢性HBV感染。公司有望按时交付关于其2020年的主要管道目标；我们期待本季度晚些时候宣布AB-729的初步安全性和有效性数据，并希望在年底之前完成AB-836的IND启用研究。”
