Assembly Biosciences Expands ABI-6250 IND Into Cholestatic Liver Diseases With Phase 2 Basket Study Planned for Q1 2027

Assembly Biosciences is extending the clinical scope of its NTCP inhibitor ABI-6250 beyond chronic hepatitis delta virus (HDV) into primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), a move that carries direct implications for IND amendment strategy, basket trial design, and the regulatory sequencing required when a mid-program asset pivots into new indications.

The mechanism underpinning the expansion is pharmacologically coherent. ABI-6250 inhibits the sodium taurocholate co-transporting polypeptide (NTCP), a hepatocyte-selective membrane protein that functions both as the HDV entry receptor and as the primary bile acid transporter into liver cells. Blocking NTCP reduces intrahepatic bile acid accumulation, the central driver of inflammation and fibrosis in cholestatic disease. Phase 1a data in healthy participants demonstrated dose-dependent elevations in plasma total bile acids, confirming target engagement consistent with NTCP inhibition. Completed chronic toxicology studies are cited as supporting longer-term dosing in Phase 2.

For regulatory affairs leads, the pre-IND meeting with the U.S. Food and Drug Administration is the operative checkpoint. Assembly Bio reports the discussion was constructive, though official meeting minutes remain pending. That distinction matters: development teams expanding an existing IND into new indications should expect the FDA's written minutes to define the evidentiary thresholds for the basket study protocol, particularly around patient stratification between PBC and PSC populations, which carry distinct disease biology and unmet-need profiles. PSC currently has no approved therapies; PBC has approved agents but a documented non-responder population.

The planned Phase 2 basket study in cholestatic liver diseases is expected to initiate in Q1 2027, subject to regulatory feedback, following the HDV Phase 2 start targeted for Q4 2026. Running two Phase 2 programs in parallel on the same compound will require careful CMC alignment, particularly around supply chain continuity and any formulation changes that could trigger comparability assessments under 21 CFR Part 211 and ICH Q10 quality system expectations.

The basket design itself introduces protocol complexity that QA and clinical operations teams will need to resolve early: endpoint selection must accommodate the differing clinical trajectories of PBC and PSC, and any adaptive elements will require pre-specified statistical frameworks acceptable to the agency.

The pending FDA meeting minutes, expected to define the regulatory path for the cholestatic indication, represent the next measurable milestone before the Q1 2027 study initiation timeline can be confirmed.

Source: Assembly Biosciences via GlobeNewswire, 22 May 2026.