Assembly Biosciences has initiated dosing in the Phase 1b portion of its clinical trial for ABI-1179, a long-acting herpes simplex virus (HSV) helicase-primase inhibitor candidate, marking a significant milestone in the development of novel treatments for recurrent genital herpes. The biotechnology company announced that the first participant has been dosed in the randomized, blinded, placebo-controlled study designed to evaluate both safety and antiviral activity in patients with recurrent genital herpes.
Study Design and Objectives
The Phase 1b study will evaluate weekly oral doses of ABI-1179 administered over a 29-day treatment period in participants seropositive for HSV-2 with recurrent genital herpes. The trial employs a 20:5 randomization ratio between ABI-1179 and placebo across up to four cohorts exploring different dose levels with pooled placebo analysis.
Antiviral activity will be assessed through multiple viral parameters, including HSV type 2 (HSV-2) shedding rate and levels of HSV-2 DNA obtained from anogenital swab samples. Clinical parameters will also be measured, including lesion recurrence rate, lesion duration, and days with lesions. These comprehensive endpoints aim to provide a thorough evaluation of the drug's therapeutic potential.
Promising Preclinical and Phase 1a Results
ABI-1179 has demonstrated encouraging preliminary data that support its advancement into Phase 1b testing. The compound exhibited low nanomolar potency against both HSV type 1 (HSV-1) and HSV-2 in vitro studies. Additionally, positive interim Phase 1a results showed a pharmacokinetic profile supporting once-weekly oral dosing in healthy participants, a significant advantage over current daily treatment regimens.
The Phase 1a portion evaluated safety, tolerability, and pharmacokinetics following single dose administration in healthy participants randomized 6:2 between ABI-1179 and placebo across up to five cohorts at different dose levels.
Concurrent Development Strategy
Assembly Biosciences is pursuing a dual-track development approach, running Phase 1b studies for both ABI-1179 and ABI-5366 concurrently. Both long-acting helicase-primase inhibitor candidates exceeded the company's target pharmacokinetic profiles in Phase 1a evaluation, leading to their advancement into Phase 1b studies. The trials utilize equivalent eligibility criteria and outcome measures and are being conducted at overlapping sites to optimize enrollment and resource utilization.
To maintain enrollment timelines while running both trials simultaneously, Assembly Bio has received clearance for an Investigational New Drug application (IND) for ABI-1179, enabling expansion of the Phase 1b study to sites in the United States. Both studies remain on track to report interim data in fall 2025.
Addressing Unmet Medical Need
"For the millions of individuals affected by recurrent genital herpes, current therapies fall short in managing the significant impact repeated outbreaks have on their lives," said Anuj Gaggar, MD, PhD, chief medical officer of Assembly Bio. "With the Phase 1b study of ABI-1179 now underway, we look forward to evaluating viral and clinical outcomes for both promising long-acting HSV investigational therapies, ABI-5366 and ABI-1179, and we remain on track for interim data from both studies in the fall of this year."
Disease Burden and Current Treatment Limitations
Genital herpes represents a significant global health challenge, with epidemiologic studies estimating over four million people in the United States and France, Germany, Italy, Spain and the United Kingdom experience recurrent genital herpes. Most people with initial symptomatic genital HSV-2 infection have three or more recurrences per year, creating substantial physical and psychological burden.
The current standard of care consists of nucleoside analogs administered either intermittently for recurrences or as daily chronic suppressive therapy. However, these treatments are only partially effective in preventing recurrences and reducing viral transmission. Notably, no new drugs have been approved in the United States or Europe to treat genital herpes for more than 25 years, highlighting the critical need for innovative therapeutic approaches.
Novel Mechanism of Action
HSV helicase-primase inhibitors represent a clinically validated mechanism that targets the viral helicase-primase complex, an essential viral enzyme complex conserved across both HSV-1 and HSV-2 with no host equivalent. This targeted approach has demonstrated potential for superior efficacy compared to nucleoside analogs in short-duration clinical studies involving participants with recurrent genital herpes.
Strategic Partnership with Gilead Sciences
Under the collaboration agreement between Assembly Bio and Gilead Sciences, Inc., Gilead maintains the right to opt in to an exclusive license for further development and commercialization of both ABI-1179 and ABI-5366. This decision will be made after reviewing the Phase 1b data package to be delivered by Assembly Bio following completion of the studies. ABI-1179 was originally contributed by Gilead under this collaboration framework.
The Phase 1a/b trial is registered at clinicaltrials.gov under identifier NCT06698575, and Assembly Bio expects to submit data from the trial for presentation at future scientific meetings. Both ABI-1179 and ABI-5366 remain investigational product candidates that have not been approved anywhere globally, with safety and efficacy yet to be established through clinical development.
