ABI-4334 / Assembly Biosci - LARVOL DELTA

Sustained off-treatment inhibition of HBV replication and HBsAg levels after long-term treatment with ABI-4334 in differentiated HepaRG cells and primary human hepatocytes (EASL 2025) - " Differentiated (d)HepaRG cells were treated from day 6 post-infection (pi) with 0.1 or 1 µM ABI-4334, 1 µM vebicorvir (VBR) or 1 µM lamivudine (3TC) for 1 month, followed by 1 month off- treatment monitoring... Durable HBsAg decreases and a lack of HBV rebound was observed after stopping long- term ABI-4334 treatment in both HepaRG cells and PHH, which could be ascribed to the depletion and/or functional inactivation of intracellular cccDNA pool in these experimental conditions."

Hepatitis B

A Study to Assess the Safety, Pharmacokinetics, and Antiviral Activity of ABI-4334 in Subjects With Chronic Hepatitis B Virus Infection (clinicaltrials.gov) - P1 | N=50 | Recruiting | Sponsor: Assembly Biosciences | Not yet recruiting ➔ Recruiting | Trial primary completion date: Apr 2025 ➔ Dec 2024

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

A Study to Assess the Safety, Pharmacokinetics, and Antiviral Activity of ABI-4334 in Subjects With Chronic Hepatitis B Virus Infection (clinicaltrials.gov) - P1 | N=50 | Not yet recruiting | Sponsor: Assembly Biosciences

New P1 trial • Hepatitis B • Hepatology • Infectious Disease • Inflammation

A First in Human Study to Assess Safety, Tolerability, Pharmacokinetics of ABI-4334 in Healthy Subjects (clinicaltrials.gov) - P1 | N=54 | Completed | Sponsor: Assembly Biosciences | Recruiting ➔ Completed

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

The safety and pharmacokinetics of ABI-4334, a novel next-generation HBV core inhibitor: interim results from a phase 1 study in healthy volunteers (EASL-ILC 2023) - P1 | "4334, a novel next-generation core inhibitor, was well tolerated in SAD cohorts when administered orally up to 100 mg. Plasma concentrations were higher than predicted by non-clinical models and exceeded in vitro EC50 values for the inhibition of cccDNA formation. Potent inhibition of HBV with daily dosing is projected."

Clinical • P1 data • PK/PD data • Gastroenterology • Gastrointestinal Disorder • Hepatitis B • Hepatology • Infectious Disease • Inflammation • Pain

Next generation core inhibitors ABI-H3733 and ABI-4334 have significantly improved potency and target coverage for both antiviral and cccDNA formation activities compared to first-generation core inhibitors (EASL-ILC 2023) - "Assembly Bio has two next generation CI candidates in Phase 1 clinical studies: ABI-H3733 (3733) and ABI-4334 (4334), which have improved potency against both MOAs compared to first-generation CIs including vebicorvir (VBR). Next generation CIs 3733 and 4334 have significantly improved coverage for both antiviral and cccDNA formation activities compared to first generation CIs. 3733 and 4334 are currently completing Phase 1b and Phase 1a studies, respectively."

A First in Human Study to Assess Safety, Tolerability, Pharmacokinetics of ABI-4334 in Healthy Subjects (clinicaltrials.gov) - P1 | N=62 | Recruiting | Sponsor: Assembly Biosciences | Not yet recruiting ➔ Recruiting

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

ABI-4334, A NOVEL HEPATITIS B VIRUS CORE INHIBITOR, ACCELERATES CAPSID ASSEMBLY AND INHIBITS CCCDNA FORMATION VIA MULTIPLE PATHWAYS (AASLD 2022) - "4334 effects on cccDNA formation via intracellular amplification were evaluated by inducing HepAD38 cells and stalling DNA synthesis with foscarnet for 4 days, then treating with 4334 for 3 days followed by Southern blot. 4334 is a potent CI with activities against cccDNA formation via incoming capsids and intracellular amplification. During early stages of HBV infection, 4334 prematurely disrupts both RC-DNA and DL-DNA containing capsids. A Phase 1a first-in-human study with 4334 is planned for 2H-2022."

Hepatitis B • Hepatology • Infectious Disease • Inflammation

A First in Human Study to Assess Safety, Tolerability, Pharmacokinetics of ABI-4334 in Healthy Subjects (clinicaltrials.gov) - P1 | N=62 | Not yet recruiting | Sponsor: Assembly Biosciences

New P1 trial • Hepatitis B • Hepatology • Infectious Disease • Inflammation

ABI-4334, a novel inhibitor of hepatitis B virus core protein, promotes formation of empty capsids and prevents covalently closed circular DNA formation by disruption of incoming capsids (EASL-ILC 2022) - "4334 is a potent CI with broad coverage across CI binding pocket variants and NrtI mutants. The activity of 4334 against pgRNA encapsidation is consistent with a class II CI. 4334 treatment results in melting of cytoplasmic HBV capsids, which prevents cccDNA formation."

Hepatitis B • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Inflammation

[VIRTUAL] PRECLINICAL CHARACTERIZATION OF ABI-4334, A NOVEL, HIGHLY POTENT CORE INHIBITOR FOR THE TREATMENT OF CHRONIC HEPATITIS B VIRUS INFECTION (AASLD 2021) - "4334 is a novel, orally bioavailable core inhibitor with single digit nM potency against pgRNA encapsidation and cccDNA formation and is predicted to achieve Cmin values at high multiples of both MOAs paEC50s. 4334 is advancing in development with a Phase 1 study planned for 2022."

Late-breaking abstract • Preclinical • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Assembly Biosciences Abstracts Selected for Presentation at the Upcoming AASLD The Liver Meeting (GlobeNewswire) - "Assembly Biosciences, Inc...announced that clinical and preclinical data from its HBV core inhibitor program will be featured in one oral and two poster presentations, including one late breaking, during the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting®. The presentations include updates from the clinical studies of vebicorvir (VBR) and ABI-H3733, as well as the newly selected preclinical core inhibitor candidate, ABI-4334. AASLD will be hosted virtually November 12-15, 2021."

P1 data • P2 data • PK/PD data • Preclinical • Hepatitis B • Infectious Disease

Assembly Bio Announces Decision to Discontinue Clinical Development of ABI-H2158 (GlobeNewswire) - "Assembly Biosciences, Inc...today announced its decision to discontinue development of ABI-H2158 (2158) following the observation of elevated ALT levels consistent with drug-induced hepatotoxicity in an ongoing Phase 2 trial....After communicating the company’s decision to the FDA, the FDA noted that 2158 would also be placed on clinical hold....VBR is being evaluated in two ongoing triple combination studies for which initial on-treatment data are anticipated during 2022. ABI-H3733 (3733) has completed its Phase 1a study and initial data is planned to be announced at an upcoming medical meeting. Additionally, the company expects to advance its recently-selected core inhibitor candidate ABI-4334 (4334) into clinical development in 2022."

Clinical data • Discontinued • New trial • Trial suspension • Hepatitis B • Infectious Disease

Assembly Bio Selects Fourth HBV Core Inhibitor Candidate for Advancement Into Clinical Development (GlobeNewswire) - "Assembly Biosciences, Inc...announced it has selected a fourth core inhibitor candidate, ABI-4334 (4334), that has been optimized for potency, to advance into clinical development. The company is conducting preclinical work, with the aim of completing regulatory filings and initiating clinical studies as soon as possible in 2022....'We’re excited to further evaluate this compound and its potential, as we plan for the start of clinical studies next year.'"

New trial • Preclinical • Hepatitis B • Infectious Disease