Assembly Biosciences reports interim Phase 1a results from trial of ABI-5366

Assembly Biosciences announced interim pharmacokinetic and safety results from healthy participants in the Phase 1a portion of its ongoing Phase 1a/b study evaluating ABI-5366, an investigational long-acting herpes simplex virus helicase-primase inhibitor candidate for recurrent genital herpes. Interim results exceeded Assembly Bio’s objectives for this Phase 1a study and support ABI-5366’s progression into Phase 1b. ABI-5366 was well-tolerated and showed a favorable safety profile with exposure of up to 70 days due to its extended PK profile. Single doses of ABI-5366 at dose levels reached in Phase 1a surpassed Assembly Bio’s target plasma concentrations for antiviral efficacy, a target established from PK modelling and projected to achieve increased efficacy compared to approved therapies. ABI-5366’s half-life across the doses evaluated to date of approximately 20 days when dosed orally supports both the company’s once-weekly oral dosing target and the evaluation of a once-monthly oral dosing profile. With these data, Assembly Bio now plans to include both weekly and monthly dosing cohorts in Phase 1b in participants with recurrent genital herpes. Screening has begun for the Phase 1b portion of the study. Study Overview: ABI-5366-101 is a randomized, blinded and placebo-controlled Phase 1a/b clinical study of ABI-5366. Part A is ongoing, evaluating the safety, tolerability and PK of ABI-5366 following single ascending dose administration in healthy participants. Dosing is complete for four cohorts in Part A, evaluating doses of 10 mg, 30 mg, 100 mg and 350 mg, with each cohort randomized 6:2 between ABI-5366 and placebo, as well as an additional cohort at 30 mg to evaluate the potential for food effect. The study follow-up period in Part A began at 70 days and has been extended to 100 days after dosing, given the observed extended PK profile of ABI-5366. The study protocol includes the potential for one additional single-dose cohort in Part A, which Assembly Bio has the option to initiate in parallel with Part B. Safety and PK data reported here reflect data available as of the cut-off date. For safety, this data follow-up period ranges from 70 days after dosing for the 10 mg and 30 mg cohorts to 13 days after dosing for the most recent cohort of 350 mg. For PK, this data follow-up period ranges from 70 days after dosing for the first cohort of 10 mg to 8 days after dosing for the most recent cohort of 350 mg. The study remains blinded and the reported interim safety data includes data from both active and placebo treatment groups reported collectively. Results Across the Part A cohorts evaluated to date, ABI-5366 had a mean half-life of approximately 20 days when dosed orally, supporting once-weekly oral dosing, the target profile for ABI-5366, as well as the potential for once-monthly oral dosing. ABI-5366 doses within the range tested are projected, with weekly or monthly dosing, to maintain the target plasma concentrations for antiviral activity established by PK modelling. Assembly Bio plans to explore both once-weekly and once-monthly oral dosing regimens in the Part B portion of the study. In these cohorts to date, ABI-5366 was well-tolerated with a favorable safety profile observed with exposure of up to 70 days. Treatment-emergent adverse events were all mild to moderate in intensity and all were considered not related to study treatment by the study investigators; there were no serious AEs in any dose arm. There were no treatment-related grade 3 or 4 laboratory abnormalities and no protocol-defined stopping criteria were met. There were no clinically significant ECG abnormalities or patterns of AEs or laboratory abnormalities noted.