ABI-5366 / Assembly Biosci, Gilead - LARVOL DELTA

Helicase-primase inhibitors as next-generation anti-HSV agents: from current clinical status to structure-activity relationships and patent coverage. (PubMed, Expert Opin Ther Pat) - "With amenamevir already approved for the treatment of VZV and HSV in Japan and with pritelivir's granted breakthrough therapy designation and priority review for the treatment of acyclovir-resistant HSV infections in immunocompromised patients, other companies have also expressed interest in small-molecule helicase-primase inhibitors (HPIs)...In parallel, the availability of several cryo-electron microscopy structures of the helicase-primase complex has enabled structure-based and computer-aided drug design, facilitating the exploration of alternative scaffolds beyond the established chemotypes. The potential opportunities and limitations of the current HPIs, as well as the different dosage forms, are discussed."

Journal • Review • Herpes Simplex • Herpes Zoster • Infectious Disease • Varicella Zoster

A Study to Assess the Safety, Pharmacokinetics, and Antiviral Activity of ABI-5366 in Healthy Participants and Participants Seropositive for HSV-2 With Recurrent Genital Herpes (clinicaltrials.gov) - P1 | N=115 | Completed | Sponsor: Assembly Biosciences | Active, not recruiting ➔ Completed

Trial completion • Herpes Simplex • Infectious Disease

ABI-5366-101: a phase Ib study of a novel, oral, long-acting, investigational HSV helicase-primase inhibitor in recurrent genital herpes (ESCMID Global 2026) - No abstract available

P1 data • Infectious Disease

Virologic analyses following treatment with ABI-5366, a novel, oral, long-acting HSV helicase-primase inhibitor in participants seropositive for HSV-2 with recurrent genital herpes (ESCMID Global 2026) - No abstract available

Infectious Disease

The safety and tolerability of ABI-5366, a novel, oral, long-acting HSV helicase-primase inhibitor in participants with recurrent genital herpes (ESCMID Global 2026) - No abstract available

Clinical • Infectious Disease

Pharmacokinetic modeling of ABI-5366, an oral, long-acting, investigational HSV helicase-primase inhibitor for identification of therapeutic drug levels and optimal dosing in participants with recurrent genital herpes (ESCMID Global 2026) - No abstract available

PK/PD data • Infectious Disease

A Study to Assess the Safety, Pharmacokinetics, and Antiviral Activity of ABI-5366 in Healthy Participants and Participants Seropositive for HSV-2 With Recurrent Genital Herpes (clinicaltrials.gov) - P1 | N=115 | Active, not recruiting | Sponsor: Assembly Biosciences | Recruiting ➔ Active, not recruiting

Enrollment closed • Herpes Simplex • Infectious Disease

Structural determinants of nervous system exposure of adibelivir (IM-250) and related herpes helicase-primase inhibitors across animal species. (PubMed, Antiviral Res) - "In diverse animal species, after single or multiple doses of helicase-primase drugs by oral or intravenous administration, only adibelivir (IM-250) achieved concentrations in the nervous system in the range of plasma or blood levels (ratio 0.5 to 4 nervous system/plasma), while other helicase-primase inhibitors with distinct structures, including amenamevir, pritelivir or ABI-5366, showed a low brain/plasma ratio of less than 0.1. In preclinical studies published so far, adibelivir was efficacious in the herpes encephalitis and neonatal animal model and reduced the reactivation competence of the neuronal latent herpes viral reservoir. Ongoing clinical trials with HPIs will show whether sufficient drug exposure in brain and ganglia will translate into more effective herpes therapies for patients."

Journal • CNS Disorders • Herpes Simplex • Infectious Disease • Keratitis • Ocular Inflammation • Ophthalmology

Evaluation of the patent portfolio for helicase-primase inhibitor ABI-5366 of Assembly biosciences inc. (PubMed, Expert Opin Ther Pat) - P1 | "With amenamevir already approved for varicella-zoster virus and herpes simplex in Japan and with pritelivir's granted breakthrough therapy designation for the treatment of acyclovir-resistant HSV infections in immunocompromised patients, the target has sparked interest in helicase-primase inhibitors...This me-too approach on the old Bayer urea series is currently in clinical phase I (NCT06385327) and the modification is the bridging of the two urea nitrogens via an alkylene linkage. The chemical structure for 1,3-disubstituted tetrahydropyrimidin-2(1 H)-one derivative ABI-5366 is presented and its potential opportunities and limitations as a long-acting oral administration or injectable depot drug compared to other HPIs are discussed."

Journal • Herpes Simplex • Herpes Zoster • Infectious Disease • Varicella Zoster

A Study to Assess the Safety, Pharmacokinetics, and Antiviral Activity of ABI-5366 in Healthy Participants and Participants Seropositive for HSV-2 With Recurrent Genital Herpes (clinicaltrials.gov) - P1 | N=146 | Recruiting | Sponsor: Assembly Biosciences | Trial completion date: Jul 2025 ➔ Dec 2025 | Trial primary completion date: Jul 2025 ➔ Dec 2025

Trial completion date • Trial primary completion date • Herpes Simplex • Infectious Disease

Preclinical profile of ABI-5366, a novel potent HSV helicase-primase inhibitor, with potential for weekly or monthly oral dosing for the treatment of recurrent genital herpes (ESCMID Global 2025) - No abstract available

Preclinical • Infectious Disease

The safety and pharmacokinetics of ABI-5366, a novel, oral, long-acting HSV helicase-primase inhibitor: Interim results from a Phase 1a/1b study in healthy participants (ESCMID Global 2025) - No abstract available

Clinical • P1 data • PK/PD data

A Study to Assess the Safety, Pharmacokinetics, and Antiviral Activity of ABI-5366 in Healthy Participants and Participants Seropositive for HSV-2 With Recurrent Genital Herpes (clinicaltrials.gov) - P1 | N=146 | Recruiting | Sponsor: Assembly Biosciences | Not yet recruiting ➔ Recruiting

Enrollment open • Herpes Simplex • Infectious Disease

A Study to Assess the Safety, Pharmacokinetics, and Antiviral Activity of ABI-5366 in Healthy Participants and Participants Seropositive for HSV-2 With Recurrent Genital Herpes (clinicaltrials.gov) - P1 | N=146 | Not yet recruiting | Sponsor: Assembly Biosciences

New P1 trial • Herpes Simplex • Infectious Disease