Assembly Biosciences to advance oral HDV drug into rare cholestatic liver diseases
Assembly Biosciences (NASDAQ:ASMB) announced plans to expand the clinical development framework for its experimental compound ABI-6250, pushing the asset beyond its initial virology target into chronic cholestatic liver conditions.
The clinical-stage biotechnology company will advance the small molecule into clinical trials for primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), broadening its operational scope to address high unmet needs in orphan liver pathologies.
ABI-6250 is an orally administered small-molecule inhibitor of the sodium taurocholate co-transporting polypeptide (NTCP).
The hepatocyte membrane protein functions as a critical transport channel for bile acids into liver cells and concurrently acts as the primary cellular entry receptor for the hepatitis delta virus (HDV).
By executing target engagement on NTCP, the therapeutic candidate is designed to block both HDV cellular entry and intracellular bile acid transport.
The latter mechanism is highly relevant to cholestatic disorders like PBC and PSC, where progressive bile acid retention triggers severe intrahepatic inflammation, tissue scarring, and subsequent liver injury.
The strategic expansion builds on preliminary safety, pharmacokinetic, and pharmacodynamic findings from a completed Phase 1a clinical trial in healthy participants.
Data from that study demonstrated robust target engagement via dose-dependent elevations in plasma total bile acids, confirming the expected biological effect of NTCP pathway inhibition.
Management also confirmed that chronic toxicology profiling has been completed, providing the necessary safety clearance to support long-term patient dosing protocols.
The pipeline acceleration will follow a dual clinical track.
Assembly Bio remains on schedule to initiate a Phase 2 clinical study evaluating ABI-6250 in chronic HDV patients in the fourth quarter of 2026.
Following this, the company expects to launch a Phase 2 basket study in cholestatic liver diseases, specifically enrolling individuals diagnosed with PBC and PSC, in the first quarter of 2027, subject to customary regulatory feedback.
Currently, therapeutic choices for these cholestatic conditions are severely constrained.
There are no approved disease-modifying therapies on the market for PSC, and a meaningful subset of patients living with PBC exhibit an inadequate response or progressive resistance to established first-line alternatives.