"We are excited to expand the ABI-6250 program into PBC and PSC, where there remains significant unmet medical need despite existing PBC therapies, and in the case of PSC, no approved treatments," said Anuj Gaggar, MD, PhD, chief medical officer of Assembly Bio. "The NTCP receptor plays an integral role in both HDV entry and bile acid transport into liver cells, making it a compelling target across multiple liver diseases. We believe ABI-6250 has the potential to address key drivers of disease pathology in these conditions and look forward to advancing clinical evaluation in these populations."

ABI-6250 is currently being evaluated for chronic HDV infection and has completed a Phase 1a clinical trial in healthy participants. It is an investigational oral small-molecule inhibitor of the sodium taurocholate co-transporting polypeptide (NTCP), a membrane protein selectively expressed on hepatocytes that facilitates bile acid transport into cells and also serves as the entry receptor for HDV infection. By inhibiting NTCP, ABI-6250 blocks the uptake of bile acids into liver cells, a mechanism directly relevant to cholestatic liver diseases, where bile acid accumulation drives liver inflammation and liver injury.

"Treatment options for cholestatic liver diseases have expanded in recent years, but important gaps remain, particularly for patients with PSC for whom no treatments currently are approved and for those with PBC who do not adequately respond to the current therapies," said Christopher Bowlus, MD, Lena Valente Professor and Chief, Division of Gastroenterology and Hepatology, University of California, Davis. "Targeting NTCP represents a mechanistically distinct approach compared to currently approved therapies, given its central role in bile acid transport. An oral agent like ABI-6250 that modulates this pathway could offer a differentiated strategy to impact disease biology and patient symptoms."

The company believes the expansion of ABI-6250 into PBC and PSC is supported by preclinical data, the compound's pharmacologic profile, and clinical findings from the Phase 1a study. These data demonstrated target engagement, including dose-dependent elevations in plasma total bile acids, consistent with NTCP inhibition. In addition, chronic toxicology studies have been completed and support the potential for longer-term dosing in planned Phase 2 trials. The company plans to initiate a Phase 2 clinical study of ABI-6250 in HDV in the fourth quarter of 2026. In addition, a Phase 2 basket study in cholestatic liver diseases, focused on PBC and PSC, is expected to begin in the first quarter of 2027, subject to regulatory feedback.

Assembly Bio recently conducted a pre-IND meeting with the U.S. Food and Drug Administration to discuss the planned development of ABI-6250 in cholestatic liver diseases. While official meeting minutes are pending, the company believes the discussion was constructive and provided helpful guidance to support advancement of the program.

PBC and PSC are chronic, autoimmune cholestatic liver diseases characterized by impaired bile flow, accumulation of bile acids in the liver and progressive liver damage. Clinical symptoms for both PBC and PSC include itch and fatigue, with development of fibrosis and cirrhosis as the diseases progress. There are multiple therapies available for the treatment of PBC; however, a significant percentage of individuals have an inadequate response to these treatments, and there remains an unmet medical need for improved treatment of PBC. There is a significant unmet medical need for the management of PSC as there are currently no approved therapies.

ABI-6250 is an investigational product candidate that has not been approved anywhere globally, and its safety and efficacy have not been established.