AB-836 / Arbutus - LARVOL DELTA

Preclinical and Clinical Antiviral Characterization of AB-836, a Potent Capsid Assembly Modulator Against Hepatitis B Virus. (PubMed, Antiviral Res) - "Furthermore, HBV DNA sequence analysis of baseline samples from the Phase 1 study revealed that 51.4% of the chronic hepatitis B participants contained at least one core polymorphism within the CAM-binding pocket, suggesting that genetic variations exist at this site. While AB-836 was discontinued due to clinical safety findings, data from the preclinical and clinical studies could help inform future optimization of HBV CAMs."

Journal • Preclinical • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Rational Design, Synthesis, and Structure-Activity Relationship of a Novel Isoquinolinone-Based Series of HBV Capsid Assembly Modulators Leading to the Identification of Clinical Candidate AB-836. (PubMed, J Med Chem) - "Based on these results, isoquinolinone derivative AB-836 was advanced into clinical development. In Phase 1b trials, AB-836 demonstrated >3 log10 reduction in serum HBV DNA, however, further development was discontinued due to the observation of incidental alanine aminotransferase (ALT) elevations."

Journal • Developmental Disorders • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Hepatitis B virus core protein variant profiles observed in chronic hepatitis B patients treated with capsid inhibitor AB-836 (EASL-ILC 2023) - "No viral breakthrough or enrichment of HBV core protein resistant variants was observed in subjects receiving AB-836 for 28 days. Multiple core protein variants at amino acid positions Y38, I105, T109, T114, and I116 were observed to occur at higher frequencies, suggesting viral plasticity at these sites."

Clinical • Hepatitis B • Hepatology • Infectious Disease • Inflammation • IFNA1

Safety, Tolerability, and Pharmacokinetics of AB-836 in Healthy Subjects and Subjects With Chronic HBV Infection (clinicaltrials.gov) - P1 | N=110 | Terminated | Sponsor: Arbutus Biopharma Corporation | Recruiting ➔ Terminated; Safety

Trial termination • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Safety, Tolerability, and Pharmacokinetics of AB-836 in Healthy Subjects and Subjects With Chronic HBV Infection (clinicaltrials.gov) - P1 | N=110 | Recruiting | Sponsor: Arbutus Biopharma Corporation | N=60 ➔ 110 | Trial completion date: Aug 2022 ➔ Feb 2023 | Trial primary completion date: Apr 2022 ➔ Jan 2023

Enrollment change • Trial completion date • Trial primary completion date • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Rational design of a novel series of HBV capsid inhibitors leading to the identification of clinical candidate AB-836 (ACS-Fall 2022) - "Initial data from a phase 1b proof of concept study in chronic hepatitis B patients receiving a once daily 100 mg dose of AB-836 for 28 days (N=4) showed robust antiviral activity with a mean reduction of 3.1 log10 in HBV DNA from baseline. The excellent preclinical profile and emerging clinical data support further development of AB-836."

Clinical • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Safety, tolerability, pharmacokinetics (PK), and antiviral activity of the 3rd generation capsid inhibitor AB-836 in healthy subjects (HS) and subjects with chronic hepatitis B (CHB) (EASL-ILC 2022) - "Single and multiple doses of AB-836 in HS and up to 100 mg QD for 28 days in CHB subjects have been generally safe and well-tolerated. Robust antiviral activity was observed at Day 28 of treatment. These results support further evaluation of AB-836 alone and in combination with other agents, including the GalNAc siRNA AB-729, in CHB subjects."

Clinical • PK/PD data • Hepatitis B • Hepatology • Infectious Disease • Inflammation • Pain • Pulmonary Disease • Respiratory Diseases

Arbutus Announces 2022 Corporate Objectives and Provides Financial Update (GlobeNewswire) - "Summary of 2022 Anticipated Key Milestones:...Announce preliminary AB-729 data in the second half of 2022 from the following three on-going Phase 2a proof-of-concept clinical trials in patients with chronic hepatitis B (HBV) infection:...Initiate a triple combination Phase 2a proof-of-concept clinical trial in the first half of 2022 to evaluate AB-729, combined with VTP-300, Vaccitech’s therapeutic vaccine, and a NA. Present at a medical conference the long-term on- and off-treatment follow-up data from our Phase 1a/1b clinical trial evaluating multiple doses and dosing schedules of AB-729. Announce data from our Phase 1a/1b clinical trial evaluating AB-836 in patients with chronic HBV in the first half of 2022. Complete IND-enabling studies with our oral PD-L1 inhibitor compound, AB-101, in the second half of 2022. Complete IND-enabling studies for AB-161, our next-generation oral HBV specific RNA destabilizer, in the second half of 2022."

New P2a trial • P1 data • P2a data • Preclinical • Hepatitis B • Infectious Disease

Preliminary Data Shows that Arbutus’ Capsid Inhibitor, AB-836 is Generally Safe and Well-Tolerated and Provides Robust Antiviral Activity (GlobeNewswire) - P1, N=60; NCT04775797; Sponsor: Arbutus Biopharma Corporation; "Arbutus Biopharma Corporation...announced preliminary data from its on-going Phase 1a/1b clinical trial demonstrating that its next generation capsid inhibitor, AB-836, is generally safe and well-tolerated in both healthy subjects and patients with cHBV and provides robust antiviral activity....Among those who received 100mg once daily for the full 28 days (n=4), robust antiviral activity was observed at Day 28 of treatment with a mean (SE) log10 change from baseline of -3.1 (0.5)...Arbutus is continuing to enroll and dose cHBV patients in Part 3 of the clinical trial and anticipates presenting additional data at a medical conference in 2022."

P1 data • Hepatitis B • Infectious Disease

[VIRTUAL] Preclinical antiviral profile of AB-836, a potent, highly selective hepatitis B virus capsid inhibitor (EASL-ILC 2021) - "AB-836 is a novel class II capsid inhibitor that showed potent, selective inhibition of HBV in vitro and in vivo, with a unique binding mode to core protein, and a favorable preclinical profile for clinical advancement."

Preclinical • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Safety, Tolerability, and Pharmacokinetics of AB-836 in Healthy Subjects and Subjects With Chronic HBV Infection (clinicaltrials.gov) - P1; N=60; Recruiting; Sponsor: Arbutus Biopharma Corporation; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Arbutus Announces Multiple Abstracts Accepted for Oral and Poster Presentations at the EASL 2021 International Liver Congress in June (GlobeNewswire) - "Arbutus Biopharma Corporation...announced that five abstracts have been accepted for presentation at the upcoming International Liver CongressTM (ILC), the Annual Meeting of the European Association for the Study of the Liver (EASL) in June 2021. Arbutus will hold a conference call at 8:00 AM ET, Monday June 28, 2021 to discuss the new data being presented at EASL. The accepted abstracts include two oral presentations, one of which is a late breaker, and three poster presentations."

Clinical data • Late-breaking abstract • Hepatitis B • Infectious Disease

Arbutus Receives Regulatory Approval to Initiate a Phase 1a/1b Clinical Trial with AB-836, an Oral Capsid Inhibitor for the Treatment of Chronic Hepatitis B Infection (Arbutus Biopharma Press Release) - "Arbutus Biopharma Corporation...announced that it has received regulatory approval to initiate a Phase 1a/1b clinical trial with AB-836, its proprietary oral capsid inhibitor for the treatment of HBV infection...'and we expect to begin dosing shortly.'"

New P1 trial • Hepatitis B • Infectious Disease

Safety, Tolerability, and Pharmacokinetics of AB-836 in Healthy Subjects and Subjects With Chronic HBV Infection (clinicaltrials.gov) - P1; N=60; Not yet recruiting; Sponsor: Arbutus Biopharma Corporation

Clinical • New P1 trial • Hepatitis B • Hepatology

A NOVEL HBV CAPSID INHIBITOR COMPOUND SERIES DEMONSTRATES IMPROVED INHIBITION OF HBV WT AND T33N CORE PROTEIN VARIANT AND SHOWS A UNIQUE BINDING MODE TO CORE PROTEIN (AASLD 2019) - "HBV capsid inhibitors from a novel chemotype showed a unique binding mode to HBV core protein when compared to previously reported X-ray structures and demonstrated improved antiviral properties in vitro in comparison to previous generation of capsid inhibitors."