Core Insights - Assembly Biosciences, Inc. announced interim data from the Phase 1a clinical trial of ABI-6250, a small molecule hepatitis delta virus (HDV) entry inhibitor, showing a mean half-life of four days and supporting a target daily oral dosing profile [1][2][4] Study Overview - The ongoing Phase 1a study, ABI-6250-101, is randomized, blinded, and placebo-controlled, evaluating safety, tolerability, and pharmacokinetics (PK) of ABI-6250 with dosing completed in various cohorts [5][6] - Doses evaluated include single doses of 5 mg and 25 mg, and multiple doses of 0.05 mg, 0.2 mg, and 1 mg, with multiple-dose cohorts receiving repeat daily dosing over 10 days [5] Pharmacokinetics - A mean half-life of approximately four days was observed for ABI-6250, supporting once-daily oral dosing [7] - Accumulation was noted in multiple-dose cohorts, with exposures on the last day of dosing reaching 6- to 7-fold higher than after the first dose [7] Biomarkers - Dose-dependent elevations of total serum bile acids (TBA) were observed in both single-dose cohorts, indicating NTCP target engagement [8][9] - In the highest single-dose cohort of 25 mg, elevated levels of coproporphyrin I (CP-1) were also noted, suggesting off-target engagement [8][11] Safety Profile - Treatment-emergent adverse events (AEs) were primarily grade 1 or 2, with no serious AEs reported [10] - One grade 2 alanine transaminase (ALT) elevation was observed in the highest single-dose cohort, with all elevations being self-limited and not associated with bilirubin or other liver injury markers [11] Future Plans - The company plans to further explore ABI-6250's pharmacologic and biologic profile in preparation for Phase 2 clinical studies, addressing the critical need for new treatment options for chronic HDV infection [4][12]