Assembly Biosciences has initiated dosing in a Phase 1a clinical trial of ABI-6250, marking a significant step toward developing the first oral treatment for chronic hepatitis delta virus (HDV) infection. The study commenced at South San Francisco-based facilities, evaluating the company's novel small molecule HDV entry inhibitor.
The Phase 1a trial will assess both single and multiple ascending doses of ABI-6250 in healthy participants, focusing on safety, tolerability, and pharmacokinetic profiles. A key aspect of the study includes monitoring serum bile acids as a biomarker of the drug's engagement with its target, the sodium taurocholate cotransporting polypeptide (NTCP) - the transporter utilized by HDV to infect liver cells.
"ABI-6250 has the potential to be the first oral therapy for cHDV, a life-threatening chronic viral infection with limited treatment options available," stated Dr. Anuj Gaggar, Chief Medical Officer of Assembly Bio. "Chronic HDV is the most severe form of viral hepatitis with 70% of individuals with cHDV progressing to cirrhosis within 10 years."
Clinical Trial Design and Objectives
The randomized, blinded, and placebo-controlled study (NCT06740474) will evaluate up to five single-dose and five multiple-dose cohorts at different dose levels. The multiple-dose phase will assess repeated administration over 10 days. This comprehensive evaluation will help determine optimal dosing for future clinical studies.
Current Treatment Landscape
The therapeutic landscape for chronic HDV infection remains limited, with only one approved therapy in the European Union and none in the United States. The current approved treatment requires daily injections and works by inhibiting NTCP, typically accompanied by well-tolerated elevations in serum bile acid levels.
Promising Preclinical Profile
ABI-6250 has demonstrated encouraging preclinical results, including:
- Low nanomolar potency across multiple HDV genotypes in vitro
- Selectivity for NTCP versus other bile acid transporters
- Pharmacokinetic characteristics supporting once-daily oral administration
The company anticipates sharing initial data from this Phase 1a study in the third quarter of 2025, potentially marking a significant advancement in HDV treatment options. If successful, ABI-6250 could offer a more convenient oral alternative to current injectable therapies, potentially improving treatment accessibility and patient compliance.
