imdusiran (AB-729) / Arbutus - LARVOL DELTA

IM-PROVE I: characterization of chronic hepatitis B (CHB) subjects with functional cure or HBV DNA suppression after completion of imdusiran plus short courses of pegylated interferon alfa-2a (IFN) and discontinuation of nucleos(t)ide analogue (NA) therapy (EASL 2025) - No abstract available

Clinical • Hepatitis B • Hepatology • Infectious Disease • Inflammation

IM-PROVE I: Rapid loss followed by transient increases in HBV RNA in chronic hepatitis B subjects during treatment with imdusiran and pegylated interferon alfa-2a is associated with HBsAg seroclearance (EASL 2025) - No abstract available

Clinical • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Long-Term Follow-up Study for Subjects With CHB Previously Treated With Imdusiran (AB729) (clinicaltrials.gov) - P=N/A | N=50 | Recruiting | Sponsor: Arbutus Biopharma Corporation | Not yet recruiting ➔ Recruiting | N=35 ➔ 50

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

SOLUBLE IMMUNE BIOMARKER PROFILING OF CHRONIC HEPATITIS B SUBJECTS TREATED WITH IMDUSIRAN IN COMBINATION WITH PEGYLATED INTERFERON ALFA REVEALS PHASES OF IMMUNE ACTIVATION (AASLD 2024) - "IDR treatment in combination with IFN was associated with distinct phases of soluble immune biomarker signatures. Immune biomarkers associated with Th1 immune activation and regulation of inflammation were observed in subjects during IDR lead-in, coinciding with the establishment of a plateau in HBsAg reduction. Secondary transient elevations of these immune biomarkers were observed to occur during IFN treatment and were followed by appearance of Th2 immune biomarker signatures that were associated with HBsAg seroconversion."

Biomarker • Clinical • Combination therapy • IO biomarker • Hepatitis B • Hepatology • Infectious Disease • Inflammation • BTLA • CD86 • IL10 • IL12A • IL13 • IL4 • IL5 • IL6 • IL7 • LAG3 • PD-1 • PD-L1

HBV TARGET SITE FOR THE RNA INTERFERENCE THERAPEUTIC IMDUSIRAN IS HIGHLY CONSERVED IN CHRONIC HEPATITIS B SUBJECTS (AASLD 2024) - "Background: Imdusiran (AB-729, IDR) is an N- Acetylgalactosamine-conjugated small interfering RNA (siRNA) currently being investigated in multiple combination studies, including pegylated interferon-alfa 2a (AB-729-201, IM-PROVE I) and the immunotherapeutic VTP-300 (AB-729-202, IM-PROVE II) for the treatment of chronic hepatitis B (CHB). The IDR target site is highly conserved in baseline samples from CHB subjects enrolled in IDR clinical studies assessed to date. In vitro testing in an HBV cell-based model confirmed retention of IDR activity against tested variants, suggesting that these SNPs have no apparent influence on HBsAg declines in subjects treated with IDR. Imdusiran has demonstrated clinical activity against HBV genotypes A-E."

Clinical • IO biomarker • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Control of Hepatitis B Virus with Imdusiran, a Small Interfering RNA Therapeutic. (PubMed, ACS Infect Dis) - "Imdusiran did not intrinsically stimulate cytokine release in healthy donor human whole blood, supportive of its mechanism of action as a direct acting RNA interference antiviral. Taken together, these data support imdusiran in combination treatment approaches toward chronic hepatitis B functional cure."

Journal • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Study Investigating the Safety and Immunogenicity of AB-729 and VTP 300 in Virologically Suppressed CHB Participants (ANZCTR) - P2 | N=62 | Active, not recruiting | Sponsor: Arbutus Biopharma | Recruiting ➔ Active, not recruiting | N=40 ➔ 62

Enrollment change • Enrollment closed • Hepatitis B • Hepatology • Infectious Disease • Inflammation • IFNG

Study of Imdusiran (AB-729) in Combination With Intermittent Dosing of Durvalumab in Subjects With Chronic HBV Infection (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Arbutus Biopharma Corporation | N=30 ➔ 0 | Trial completion date: Jul 2027 ➔ Aug 2024 | Recruiting ➔ Withdrawn | Trial primary completion date: Feb 2027 ➔ Aug 2024

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

i-LIVER: Intrahepatic and Peripheral Responses to Imdusiran (AB-729) in Chronic Hepatitis B (clinicaltrials.gov) - P2 | N=10 | Recruiting | Sponsor: University of Maryland, Baltimore | Not yet recruiting ➔ Recruiting

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

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 (EASL-ILC 2024) - "Study AB-729-202 is an ongoing, randomized, double-blinded Phase 2a study assessing the safety, pharmacodynamics and immunogenicity of repeat doses of imdusiran followed by VTP-300 ± low dose nivolumab or placebo in nucleos(t)ide analogue (NA) suppressed, non-cirrhotic CHB subjects. Repeat dosing of imdusiran for 24 weeks followed by VTP-300 was well-tolerated and contributes to the maintenance of lower HBsAg levels compared to placebo in subjects who have reached EOT and follow up Wk 60. More subjects who received VTP-300 have qualified to stop NA therapy at EOT and all remain off therapy. Additional on-treatment, follow-up and NA discontinuation data including HBV parameters and immunology data will be presented."

Clinical • Hepatitis B

VTP-300 immunotherapeutic, plus low dose PD-1 inhibitor, nivolumab, continues to show meaningful, sustained reductions in HBsAg levels (EASL-ILC 2024) - "Preliminary safety data suggest that VTP-300 in combination with low dose nivolumab has been generally well tolerated and has resulted in meaningful, sustained HBsAg reductions, particularly in participants with baseline HBsAg levels ≤200IU/mL. We believe that VTP-300 is a promising immunotherapeutic candidate for enhancing CHB functional cure rates. VTP-300 is also being investigated in combination with a siRNA inhibitor, imdusiran."

IO biomarker • Endocrine Disorders • Hepatitis B • Hepatology • Immunology • Infectious Disease • Inflammation

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 (EASL-ILC 2024) - "HBsAg ≤ LLOQ with detectable anti-HBs was observed at EOT in 28% of subjects who received 4 or 6 doses of imdusiran plus 24 weeks of IFN, but in 0 subjects who received 4 or 5 doses of imdusiran plus 12 weeks of IFN. The study remains ongoing and additional EOT data, durability of EOT HBsAg loss, and preliminary immunology data for a subset of study subjects will be presented."

Clinical • Combination therapy • Hepatitis B • Infectious Disease

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 (EASL-ILC 2024) - "HBsAg ≤ LLOQ with detectable anti-HBs was observed at EOT in 28% of subjects who received 4 or 6 doses of imdusiran plus 24 weeks of IFN, but in 0 subjects who received 4 or 5 doses of imdusiran plus 12 weeks of IFN. The study remains ongoing and additional EOT data, durability of EOT HBsAg loss, and preliminary immunology data for a subset of study subjects will be presented."

Clinical • Combination therapy • Hepatitis B • Infectious Disease

Study of Imdusiran (AB-729) in Combination With Intermittent Dosing of Durvalumab in Subjects With Chronic HBV Infection (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: Arbutus Biopharma Corporation | Not yet recruiting ➔ Recruiting

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

i-LIVER: Intrahepatic and Peripheral Responses to Imdusiran (AB-729) in Chronic Hepatitis B (clinicaltrials.gov) - P2 | N=10 | Not yet recruiting | Sponsor: University of Maryland, Baltimore | Trial completion date: Jul 2026 ➔ Jul 2027 | Initiation date: Jan 2024 ➔ May 2024 | Trial primary completion date: Dec 2025 ➔ Dec 2026

Trial completion date • Trial initiation date • Trial primary completion date • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Long-Term Follow-up Study for Subjects With CHB Previously Treated With Imdusiran (AB729) (clinicaltrials.gov) - P=N/A | N=35 | Not yet recruiting | Sponsor: Arbutus Biopharma Corporation

New trial • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Study of Imdusiran (AB-729) in Combination With Intermittent Dosing of Durvalumab in Subjects With Chronic HBV Infection (clinicaltrials.gov) - P2 | N=30 | Not yet recruiting | Sponsor: Arbutus Biopharma Corporation

Combination therapy • New P2 trial • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Open-Label Study of AB-729, Nucleos(t)Ide Analogue and Pegylated Interferon Alfa-2a in Subjects With Chronic Hepatitis B Infection (clinicaltrials.gov) - P2 | N=43 | Active, not recruiting | Sponsor: Arbutus Biopharma Corporation | Trial primary completion date: Oct 2023 ➔ May 2024

Trial primary completion date • Hepatitis B • Hepatology • Infectious Disease • Inflammation • IFNA1

i-LIVER: Intrahepatic and Peripheral Responses to Imdusiran (AB-729) in Chronic Hepatitis B (clinicaltrials.gov) - P2 | N=10 | Not yet recruiting | Sponsor: University of Maryland, Baltimore

New P2 trial • Hepatitis B • Hepatology • Infectious Disease • Inflammation

A Study Evaluating Treatment Regimens Containing Vebicorvir (ABI-H0731) in Participants With Chronic Hepatitis B Infection (clinicaltrials.gov) - P2 | N=65 | Terminated | Sponsor: Assembly Biosciences | Phase classification: P2a ➔ P2

Phase classification • Hepatitis B • Hepatology • Infectious Disease • Inflammation

PRELIMINARY PHARMACODYNAMICS AND SAFETY OF REPEAT DOSING OF IMDUSIRAN (AB-729) FOLLOWED BY VTP-300 OR PLACEBO IN VIRALLY-SUPPRESSED, NON-CIRRHOTIC SUBJECTS WITH CHRONIC HEPATITIS B (CHB) (AASLD 2023) - "Preliminary data suggest that repeat dosing of imdusiran for 24 weeks followed by VTP-300 was welltolerated and may contribute to prolonged HBsAg reductions compared to placebo. Additional on-treatment and follow-up data including HBV parameters and immunology data will be presented."

Clinical • Late-breaking abstract • PK/PD data • Hepatitis B • Hepatology • Infectious Disease • Inflammation • CD4 • CD8

PRELIMINARY OFF-TREATMENT RESPONSES FOLLOWING 48 WEEKS OF VEBICORVIR, NUCLEOS(T)IDE REVERSE TRANSCRIPTASE INHIBITOR, AND AB-729 COMBINATION IN VIROLOGICALLY SUPPRESSED PATIENTS WITH HEPATITIS B E ANTIGEN NEGATIVE CHRONIC HEPATITIS B: ANALYSIS FROM AN OPEN-LABEL PHASE 2 STUDY (AASLD 2023) - P2a | "Treatments were well tolerated. Available data indicate that adding VBR to AB-729+NrtI does not result in significantly greater on- or post-treatment improvements in markers of active HBV infection vs AB-729+NrtI."

Clinical • P2 data • Hepatitis B • Hepatology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

BASELINE NUCLEOTIDE POLYMORPHISMS WITHIN HBV TARGET SITE IN CHRONIC HEPATITIS B SUBJECTS DO NOT IMPACT HBsAg REDUCTIONS MEDIATED BY RNA INTERFERENCE THERAPEUTIC AB-729 (AASLD 2023) - "SNPs in the AB-729 HBV target site were identified in sequences obtained from a publicly available database and were observed at baseline in some CHB subjects in AB-729-001. In vitro testing in an HBV cell-based model confirm retention of AB-729 activity against tested variants, suggesting that these SNPs have no apparent influence on individual or mean HBsAg declines observed in subjects treated with AB-729."

Clinical • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Preliminary safety and antiviral activity of AB-729 combination treatment with pegylated interferon alfa-2a in virally suppressed, HBeAg-negative subjects with chronic HBV infection (EASL-ILC 2023) - "AB-729 treatment in virally suppressed CHB subjects was well tolerated and led to mean HBsAg declines of > 1.6 log10 after 24 weeks of treatment, comparable to other AB-729 studies. HBsAg levels < 100 IU/mL were noted in 88% of the subjects. This interim data analysis suggests addition of IFN was well tolerated, and AB-729 + IFN appears to result in continued HBsAg declines in most subjects with 2 subjects reaching HBsAg <LLOQ during IFN treatment, but more data is needed to assess the overall impact on HBsAg responses."

Clinical • Late-breaking abstract • Hematological Disorders • Hepatitis B • Infectious Disease • Neutropenia

A Study Evaluating Treatment Regimens Containing Vebicorvir (ABI-H0731) in Participants With Chronic Hepatitis B Infection (clinicaltrials.gov) - P2a | N=65 | Terminated | Sponsor: Assembly Biosciences | Trial completion date: Jan 2024 ➔ Mar 2023 | Active, not recruiting ➔ Terminated | Trial primary completion date: Jan 2024 ➔ Feb 2023; Sponsor decision

Trial completion date • Trial primary completion date • Trial termination • Hepatitis B • Hepatology • Infectious Disease • Inflammation