Assembly Biosciences, Inc. announced that the company will present new preclinical data from multiple hepatitis B virus (HBV) and hepatitis D virus (HDV) pipeline programs at the 2023 International HBV Meeting taking place in Kobe, Japan, September 19-23, 2023. At the meeting, one oral presentation will highlight progress in the company?s HBV/HDV oral entry inhibitor program including activity, selectivity and pharmacokinetic (PK) data that support advancement towards development candidate nomination. A second oral presentation reports new data for ABI-4334 (4334), Assembly Bio?s most potent capsid assembly modulator (CAM) with a potential best-in-class profile, describing the prevention of HBV DNA integration in vitro.

The poster presentation, from the company?s interferon-a receptor (IFNAR) agonist program, characterizes small molecule IFNAR agonists that closely mimic interferon-a?s signaling. HBV/HDV Entry Inhibitor Program: HDV is a satellite virus only found in the presence of HBV infection and is considered the most severe form of viral hepatitis. In an oral presentation entitled ?Pre-clinical profiling of a novel class of orally bioavailable small molecules potently inhibiting hepatitis B and D virus entry,?

the company will present data on a novel class of highly potent, orally bioavailable HBV/HDV entry small molecule inhibitors with favorable drug-like properties. One compound selected for further characterization exhibited potent activity against multiple HBV and HDV genotypes and selective inhibition of sodium taurocholate co-transporting polypeptide (NTCP) compared to other bile acid transporters. This compound further exhibited a favorable PK/pharmacodynamic preclinical profile supporting the potential for once daily dosing.

Assembly Bio anticipates nominating a clinical development candidate from the HBV/HDV entry inhibitor program in 2023. Next-Generation HBV CAM Candidate ABI-4334: 4334, which has completed Phase 1a evaluation, is a novel, orally bioavailable investigational next-generation CAM that exhibits nanomolar (nM) potency against pgRNA encapsidation and covalently closed circular (ccc)DNA formation in vitro. In patients with chronic HBV infection, HBV DNA integration has been linked to the development of liver cancer.

In the oral presentation entitled ?ABI-4334, a novel inhibitor of hepatitis B virus core protein, disrupts DL-DNA containing capsids and prevents HBV DNA integration,? data show that in vitro 4334 disrupts RC (relaxed circular)- and DL (duplex linear)-DNA capsid formation at nM levels and inhibits HBV DNA integration in a dose-proportional manner as shown by inverse PCR and next-generation sequencing analyses?. Based on the Phase 1a PK data, the target plasma levels of 4334 required for inhibition of HBV DNA integration in these models are achievable.

Assembly Bio?s IFNAR agonist program seeks to engage IFNa signaling using an orally bioavailable liver-focused small molecule approach to improve tolerability. The poster entitled ?Pre-clinical characterization of novel liver-focused small molecules efficiently inhibiting hepatitis B virus by activating type I interferon signaling,? features preclinical data on a novel class of IFNAR agonists that inhibit HBV infection and replication.

In vivo analysis of a compound from the series demonstrates that it closely mimics IFNa activity as measured by activating IFN-stimulated response element signaling and inducing the JAK-STAT pathway in the liver and PBMCs. PK data from the same compound exhibit desirable liver exposure and favorable oral bioavailability. Lead optimization of multiple IFNAR agonists is ongoing.