Assembly Biosciences, Inc. announced new data for ABI-6250, the company?s orally bioavailable, small molecule hepatitis D virus (HDV) entry inhibitor candidate, featured in a poster presentation at the European Association for the Study of the Liver (EASL) Congress?, taking place June 5-8, 2024, in Milan, Italy. The poster presentation ?Preclinical profiling of ABI-6250, a novel orally bioavailable small-molecule therapeutic candidate for the treatment of chronic hepatitis D? will highlight preclinical data that support the advancement of ABI-6250 into Phase 1 clinical studies. Chronic HDV infection is considered the most serious form of viral hepatitis, and can result in liver cirrhosis, liver cancer, decompensated liver disease or death.

ABI-6250 acts to prevent the entry of HDV into cells by blocking access to the sodium taurocholate cotransporting polypeptide (NTCP) bile acid transporter, which is a clinically validated target for HDV infection. Results from preclinical evaluation included in this presentation demonstrate that ABI-6250 can effectively inhibit, at low nanomolar levels, HDV infection of the most prevalent genotypes (HDV-1,-2 and-3) in HepG2-NTCP cells. ABI-6250 also effectively inhibited NTCP-mediated bile acid uptake and demonstrated selectivity for the NTCP bile transporter versus other transporters in vitro.

In vivo, ABI-6250 elevated total bile acids, indicating NTCP target engagement without increasing biomarkers for inhibition of other transporters, supporting the selectivity seen in vitro and providing a biomarker for target engagement in Phase 1a studies. The presentation also describes the preclinical pharmacokinetic (PK) profile of ABI-6250, which supports low, once-daily oral dosing in individuals with chronic HDV.