Assembly Biosciences Reports Positive Interim Phase 1a Results for ABI-5366 Helicase-Primase Inhibitor

Assembly Biosciences, Inc., a biotechnology firm focusing on viral disease therapeutics, has announced promising interim results from the Phase 1a portion of a clinical trial for ABI-5366. This investigational drug is a long-acting HSV helicase-primase inhibitor aimed at treating recurrent genital herpes. The interim findings have surpassed the company's initial goals, clearing the way for the progression to Phase 1b of the study.

The Phase 1a trial assessed the safety, tolerability, and pharmacokinetics (PK) of ABI-5366 in healthy volunteers. Remarkably, the drug was well-tolerated with a favorable safety profile observed over an exposure period of up to 70 days. The half-life of approximately 20 days supports the feasibility of once-weekly or even once-monthly oral dosing. These characteristics were deemed sufficient to move forward with testing in participants with recurrent genital herpes.

Single doses of ABI-5366 in Phase 1a reached plasma concentrations that exceed the levels considered necessary for antiviral efficacy, established through PK modeling. These concentrations suggest that ABI-5366 could offer enhanced efficacy compared to existing therapies. Consequently, Assembly Bio plans to investigate both weekly and monthly dosing regimens in the forthcoming Phase 1b segment of the study. Participant screening for Phase 1b has already commenced.

Jason Okazaki, CEO of Assembly Bio, expressed eagerness about the interim results, which align with the company’s strategy to innovate in the treatment of recurrent genital herpes. He emphasized that the current standard of suppressive therapy falls short in preventing recurrences and that no new treatments have been approved in decades. Okazaki believes the promising PK profile of ABI-5366 could significantly advance treatment options.

Dr. Anna Wald from the University of Washington underscored the urgent need for new chronic suppressive therapies for recurrent genital herpes, which has significant physical and psychological impacts. She is keen to see further data that could validate ABI-5366 as a superior alternative to existing treatments.

The Phase 1a part of the study included multiple cohorts receiving different doses of ABI-5366—10 mg, 30 mg, 100 mg, and 350 mg. Each cohort was randomized in a 6:2 ratio between the drug and a placebo, with an additional cohort to assess the drug's potential food effects. The follow-up period extended to 100 days owing to the drug's extended PK profile. No serious adverse events (AEs) were reported, and all observed AEs were mild to moderate, deemed unrelated to the treatment.

Looking ahead, Phase 1b will include participants positive for HSV-2 and experiencing recurrent genital herpes. This phase aims to evaluate multiple ascending doses of ABI-5366, administered either weekly or monthly over 29 days. Participants will be randomized 20:5 between the drug and placebo across four cohorts. The primary objectives will be to assess safety, tolerability, and PK, as well as to measure antiviral activity through various clinical parameters including lesion recurrence rates and viral shedding.

Recurrent genital herpes, caused by HSV, is a chronic condition that leads to painful lesions and carries significant psychological and social burdens. The current standard treatment involves nucleoside analogs, which are only partially effective in preventing recurrences and reducing virus transmission. There hasn't been a new drug approved for this condition in the United States or Europe for over 25 years.

ABI-5366 targets the viral helicase-primase complex, a crucial enzyme for HSV replication that has no equivalent in humans. This mode of action has shown potential for superior efficacy compared to existing nucleoside analogs in short-duration clinical studies.

Assembly Biosciences is committed to developing novel therapeutics for serious viral diseases. The company is led by a team experienced in virologic drug development and aims to improve outcomes for patients with conditions like herpesvirus, hepatitis B, and hepatitis delta virus infections. Further details about the trial are available on clinicaltrials.gov under the identifier NCT06385327.