ABI-H3733 / Assembly Biosci, BeiGene - LARVOL DELTA

A Study to Assess the Safety, Pharmacokinetics, and Antiviral Activity of ABI-H3733 in Subjects With Chronic Hepatitis B Virus Infection (clinicaltrials.gov) - P1b | N=31 | Completed | Sponsor: Assembly Biosciences | Active, not recruiting ➔ Completed | N=50 ➔ 31

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

Safety, pharmacokinetics, and antiviral activity of the next-generation hepatitis B core inhibitor ABI-H3733 in patients with hepatitis B e antigen negative chronic hepatitis B infection: preliminary results from a randomized, blinded, Phase 1b study (EASL-ILC 2023) - P1b | "3733 was well tolerated at doses up to 50 mg QD for 28 days. All AEs and lab abnormalities were Grade 1 or 2, with no serious AEs, treatment discontinuations, or deaths. No ALT elevations were observed."

Clinical • P1 data • PK/PD data • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Safety, pharmacokinetics, and antiviral activity of the next-generation hepatitis B core inhibitor ABI-H3733 in patients with hepatitis B e antigen negative chronic hepatitis B infection: preliminary results from a randomized, blinded, Phase 1b study (EASL-ILC 2023) - P1b | "3733 was well tolerated at doses up to 50 mg QD for 28 days. All AEs and lab abnormalities were Grade 1 or 2, with no serious AEs, treatment discontinuations, or deaths. No ALT elevations were observed."

Clinical • P1 data • PK/PD data • Hepatitis B • Hepatology • Infectious Disease • Inflammation

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 Study to Assess the Safety, Pharmacokinetics, and Antiviral Activity of ABI-H3733 in Subjects With Chronic Hepatitis B Virus Infection (clinicaltrials.gov) - P1b | N=50 | Active, not recruiting | Sponsor: Assembly Biosciences | Recruiting ➔ Active, not recruiting | Trial completion date: Jan 2023 ➔ Apr 2023 | Trial primary completion date: Jan 2023 ➔ Apr 2023

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

Improving the pharmacokinetic profile of the hepatitis B virus core inhibitor ABI-H3733 following oral administration: results from new formulation activities (EASL-ILC 2022) - "Based on the relative PK data in the dog model, T2 formulation is expected to have similar 3733 exposure as the LF in humans, with predicted Cmin approximately 150- and 29-fold higher than the paEC50 for pgRNA encapsidation and cccDNA formation, respectively. The improved T2 formulation will be used in an upcoming Phase 1b study conducted with cHBV patients."

PK/PD data • Hepatitis B • Hepatology • Infectious Disease • Inflammation

A Study to Assess the Safety, Pharmacokinetics, and Antiviral Activity of ABI-H3733 in Subjects With Chronic Hepatitis B Virus Infection (clinicaltrials.gov) - P1b | N=50 | Recruiting | Sponsor: Assembly Biosciences

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

Assembly Biosciences Outlines Anticipated 2022 Pipeline Development Milestones (GlobeNewswire) - "Assembly Biosciences, Inc...today outlined anticipated progress and milestones for its development pipeline in 2022....1H 2022...Complete enrollment for the two ongoing triple combination studies with VBR + NrtI and AB-729, Arbutus Biopharma’s RNAi therapeutic candidate, and with VBR + NrtI + PEG-IFNα. Initiate triple combination cohort with VBR + NrtI and ATI-2173, Antios Therapeutics’ investigational active site polymerase inhibitor nucleotide (ASPIN). Initiate Phase 1b study of ABI-H3733 in patients with chronic HBV infection...2H 2022...Report initial on-treatment data from triple combination cohort with VBR + NrtI and ATI-2173; Report initial Phase 1b data for ABI-H3733."

Clinical data • Enrollment status • New P1 trial • P1 data • Trial status • Hepatitis B • Infectious Disease

Assembly Biosciences Presents New Data at AASLD The Liver Meeting Highlighting the Progress of its HBV Core Inhibitor Portfolio (Yahoo Finance) - "ABI-H3733 shows favorable pharmacokinetics and safety in Phase 1a study; Phase 1b study expected to begin in 2022...A Phase 1b study evaluating 3733 in patients with chronic HBV infection is planned to start in 2022."

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

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

[VIRTUAL] SAFETY AND PHARMACOKINETICS OF ABI-H3733, A NOVEL 2nd GENERATION HBV CORE PROTEIN INHIBITOR: RESULTS FROM A PHASE 1a STUDY IN HEALTHY VOLUNTEERS (AASLD 2021) - "3733, a novel 2nd-generation core inhibitor, was safe, well tolerated with a favorable PK profile following single and multiple oral doses. Plasma concentrations exceeded in vitro EC50 values for inhibition of cccDNA formation and potent inhibition of HBV with QD dosing is projected . Additional solid dosage forms are being evaluated to provide comparable exposures to those observed with the oral liquid formulation ."

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

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

[VIRTUAL] Second generation Hepatitis B Virus core inhibitors ABI-H2158 and ABI-H3733 have enhanced potency and target coverage for both antiviral inhibition and covalently closed circular DNA establishment activities (EASL-ILC 2021) - "We currently have 3 core inhibitors in clinical development: vebicorvir (VBR, Phase 2), ABI-H2158 (2158, Phase 2) and ABI-H3733 (3733, Phase 1)... VBR, 2185, and 3733 achieve plasma concentrations significantly above EC50 and paEC50 for antiviral activity. The second generation compounds 2158 and 3733 show enhanced potency and exposures that cover cccDNA prevention activity at significant multiples of paEC50 at Cmin."

Hepatitis B • Hepatology • Infectious Disease • Inflammation

Assembly Biosciences Presents Data from HBV Core Inhibitor Programs at the International Liver Congress EASL 2021 (GlobeNewswire) - P2, N=92; NCT03780543; P2, N=73; NCT03576066; Sponsor: Assembly Biosciences; "Assembly Biosciences, Inc...announced data from its three clinical-stage core inhibitor programs, vebicorvir (VBR or ABI-H0731), ABI-H2158 (2158), and ABI-H3733 (3733), in an oral presentation and two poster presentations during the International Liver Congress™ 2021, the Annual Meeting of the European Association for the Study of the Liver (EASL), taking place virtually June 23-26, 2021...data evaluating human plasma and estimated liver concentrations of VBR, 2158, and 3733 in relation to their respective protein-adjusted EC50 values in primary human hepatocytes...combination therapy with VBR and NrtI for an extended period was well-tolerated and resulted in deep virologic suppression, but did not result in sustained virologic response in any patient who met prospective treatment stopping criteria."

Clinical data • P2 data • Hepatitis B • Infectious Disease

Assembly Biosciences to Present Data from HBV Core Inhibitor Programs at The International Liver Congress EASL 2021 (GlobeNewswire) - P2, N=73; NCT03576066; P2, N=92; NCT03780543; Sponsor: Assembly Biosciences; "Assembly Biosciences, Inc...announced that three abstracts have been accepted for presentation during the International Liver Congress™ 2021, the Annual Meeting of the European Association for the Study of the Liver (EASL) taking place virtually June 23-26, 2021. During the meeting, data from Assembly Bio’s three core inhibitor programs, vebicorvir (VBR), ABI-H2158 (2158) and ABI-H3733 (3733), will be featured in an oral presentation and two poster presentations...Discontinuation of VBR+NrtI treatment was well-tolerated, but sustained virologic response was not achieved. Further data analyses suggest core-related antigen level may be important in future discontinuation criteria. Other studies with VBR+NrtI in multi-drug combinations will evaluate potential finite treatment regimens."

Clinical data • P2 data • Hepatitis B • Infectious Disease

A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABI-H3733 in Healthy Adults (clinicaltrials.gov) - P1; N=120; Completed; Sponsor: Assembly Biosciences; Recruiting ➔ Completed

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

[VIRTUAL] AMINO ACID SUBSTITUTIONS IN THE INHIBITOR BINDING POCKET OF HBV CORE PROTEIN CONFER DIFFERENTIAL CHANGES IN SUSCEPTIBILITY TO THREE GENERATIONS OF HBV CORE INHIBITORS (AASLD 2020) - "Here we describe the in vitro resistance profiles of vebicorvir (VBR; ABI-H0731), ABI-H2158 (2158), and ABI-H3733 (3733), 3 generations of structurally distinct core inhibitors with increasing in vitro potency against encapsidation of viral RNA and delivery of existing nucleocapsids to establish cccDNA...Transfected cells were treated with VBR, 2158, 3733 or entecavir (ETV) for 1 week after which the amount of replicating HBV DNA in the cells was evaluated by qPCR... Although all HBV core inhibitors are known to bind the same pocket, specific amino acid substitutions in the region confer differential changes in the resistance profile of structurally distinct small molecules suggesting that specific interactions between the protein and the inhibitors modulate drug susceptibility. ETV retains activity against all tested core protein mutations suggesting that combination therapy with NrtIs may prevent viral breakthrough due to pre-existence or potential emergence of core..."

Late-breaking abstract

Assembly Biosciences Reports Second Quarter 2020 Financial Results and Recent Highlights (GlobeNewswire) - "China Collaboration with BeiGene: On July 20, 2020, Assembly announced its license and collaboration agreement with BeiGene, Ltd. for Assembly’s portfolio of three clinical-stage core inhibitors (ABI-H0731, ABI-H2158, ABI-H3733) in China including Hong Kong, Macau and Taiwan; Assembly received $40 million upfront and is eligible to receive approximately $500 million in total potential future milestone payments....BeiGene will contribute the initial funding for clinical development in China, with development costs for the territory shared equally thereafter."

Licensing / partnership • Hepatitis B

A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABI-H3733 in Healthy Adults (clinicaltrials.gov) - P1; N=120; Recruiting; Sponsor: Assembly Biosciences; Not yet recruiting ➔ Recruiting; Trial completion date: Jul 2020 ➔ Nov 2020; Trial primary completion date: Jul 2020 ➔ Nov 2020

Clinical • Enrollment open • Trial completion date • Trial primary completion date • Hepatitis B • Infectious Disease

A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABI-H3733 in Healthy Adults (clinicaltrials.gov) - P1; N=120; Not yet recruiting; Sponsor: Assembly Biosciences

Clinical • New P1 trial