Assembly Biosciences presented preclinical and in vitro data for two hepatitis drug candidates, ABI-6250 and ABI-4334, at the European Association for the Study of the Liver (EASL) Congress. ABI-6250, an oral HDV entry inhibitor, is currently in Phase 1a trials, with results expected in Q3 2025, while ABI-4334, a next-generation capsid assembly modulator (CAM) for HBV, is in Phase 1b with data anticipated in the first half of 2025. The company aims to address the unmet needs of patients with chronic viral hepatitis, particularly HDV and HBV, which are leading causes of liver disease and currently lack effective curative treatments.
The data presented for ABI-6250 is particularly noteworthy because it addresses a severe form of viral hepatitis with limited treatment options. Current HDV therapies often involve daily injections, whereas ABI-6250 offers the potential for a more convenient once-daily oral administration. This is critical for improving patient compliance and quality of life. The preclinical studies also highlight the drug’s specific targeting of the NTCP transporter, a key entry point for HDV and HBV, minimizing potential off-target effects. This focused mechanism of action holds promise for a more targeted and effective treatment approach. The ongoing Phase 1a trial will be crucial in validating these preclinical findings in humans and determining the clinical viability of total bile acids as a marker of target engagement.
Preclinical studies of ABI-6250 demonstrate its ability to inhibit both HDV and HBV at low nanomolar concentrations, indicating high potency. The drug also showed minimal impact on cell viability and selective inhibition of the NTCP transporter compared to other transporters. In vivo studies further confirmed selective NTCP engagement. For ABI-4334, in vitro studies revealed a durable reduction in HBV nucleic acids and antigens in human hepatocytes following a month-long treatment. This data suggests the potential for long-term suppression of HBV replication, which is a crucial factor in achieving functional cures for chronic HBV infection.
These developments suggest a potential shift in the treatment landscape for viral hepatitis. The emergence of new oral therapies like ABI-6250 could significantly improve treatment accessibility and patient adherence for chronic HDV. Similarly, the development of next-generation CAMs like ABI-4334 offers hope for more effective long-term management and potentially curative treatments for chronic HBV. The upcoming clinical trial data for both candidates will be critical in assessing their true potential and determining their future roles in combating these debilitating viral infections.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
