SOUTH SAN FRANCISCO, Calif., May 22, 2026
Assembly Biosciences announced plans to expand the clinical development of ABI-6250, its investigational oral small-molecule NTCP inhibitor, into primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), broadening the program beyond chronic hepatitis delta virus (HDV) infection into cholestatic liver diseases. The company expects to initiate a Phase 2 basket study focused on PBC and PSC during the first quarter of 2027, following ongoing development activities in HDV.
The expansion marks a significant strategic step for Assembly Bio as it seeks to address diseases with major unmet medical needs, particularly PSC, where no approved therapies currently exist. The company believes ABI-6250’s mechanism of action could provide a differentiated approach in targeting bile acid transport and liver inflammation across multiple chronic liver conditions.
ABI-6250 Targets NTCP Pathway in Liver Disease
ABI-6250 is an investigational oral inhibitor of the sodium taurocholate co-transporting polypeptide (NTCP) receptor, a membrane protein expressed on hepatocytes that plays a central role in bile acid transport into liver cells and also serves as the entry receptor for hepatitis delta virus infection.
By blocking NTCP activity, ABI-6250 reduces bile acid uptake into liver cells, a mechanism considered highly relevant in cholestatic liver diseases such as PBC and PSC, where toxic bile acid accumulation contributes to inflammation, fibrosis, and progressive liver damage.
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Assembly Bio Chief Medical Officer Anuj Gaggar, MD, PhD, stated that the company believes the NTCP receptor represents a compelling therapeutic target across several liver diseases due to its dual role in HDV infection and bile acid regulation. He noted that ABI-6250 could potentially address important drivers of disease pathology while expanding treatment options for patients with limited therapeutic alternatives.
The company also highlighted that ABI-6250 has completed a Phase 1a clinical study in healthy volunteers, where clinical findings demonstrated successful target engagement through dose-dependent increases in plasma bile acid levels consistent with NTCP inhibition.
Growing Need for New PBC and PSC Therapies
Primary biliary cholangitis and primary sclerosing cholangitis are chronic autoimmune liver diseases characterized by impaired bile flow, bile acid accumulation, progressive fibrosis, and eventual cirrhosis. Patients frequently experience severe symptoms including fatigue and chronic itching, while long-term disease progression can lead to liver failure and transplantation.
Although several therapies are currently approved for PBC, a significant portion of patients fail to achieve adequate responses to available treatments. In PSC, there are still no approved therapies, creating a substantial unmet medical need within hepatology.
Christopher Bowlus, MD, Chief of Gastroenterology and Hepatology at the University of California, Davis, stated that targeting NTCP offers a mechanistically distinct strategy compared with currently approved liver disease treatments. He added that an oral therapy such as ABI-6250 could potentially impact both disease biology and patient symptoms through modulation of bile acid transport pathways.
Phase 2 Development Planned for 2026 and 2027
Assembly Bio plans to initiate a Phase 2 clinical trial in chronic HDV infection during the fourth quarter of 2026, followed by the planned cholestatic liver disease basket study in early 2027. The company recently completed a pre-IND meeting with the U.S. Food and Drug Administration regarding the proposed cholestatic liver disease development program and described the regulatory discussion as constructive.
The company stated that preclinical findings, pharmacologic data, and completed chronic toxicology studies support the potential for longer-term dosing of ABI-6250 in future studies.
Assembly Bio continues to focus on developing innovative small-molecule therapies targeting viral and liver diseases, including HDV, hepatitis B virus (HBV), herpesvirus infections, and cholestatic liver disorders. The expansion of ABI-6250 into broader liver disease indications strengthens the company’s position within the growing hepatology therapeutics market while addressing areas where treatment options remain highly limited.
Source: Assembly Biosciences, press release
