IM-250 / Innovative Molecules - LARVOL DELTA

Susceptibility of clinical isolates, laboratory-adapted and drug-resistant herpes simplex virus strains to helicase-primase inhibitor adibelivir (IM-250) and its synergy in combination therapy with acyclovir, penciclovir and foscarnet. (PubMed, Antiviral Res) - "Current treatment relies on nucleoside analogs such as acyclovir, valacyclovir or famciclovir. Adibelivir retains activity against nucleoside-resistant HSV strains and exhibits synergistic antiviral effects when combined with acyclovir, penciclovir and foscarnet in vitro. These results support clinical evaluation of adibelivir as a therapeutic option for HSV infections and as a candidate for combination therapy."

Journal • CNS Disorders • Herpes Simplex • Infectious Disease • Transplantation

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 UPLC-MS/MS assay for the quantification of the novel viral helicase-primase drug candidate adibelivir (IM-250) in human specimen. (PubMed, J Chromatogr B Analyt Technol Biomed Life Sci) - "Additionally, the assay was adapted for the quantification of adibelivir in urine with a lowered calibration range of 0.1-100 ng/mL. The present work provides a fully validated assay for pharmacokinetic analyses of adibelivir in clinical development, e.g. in its first-in-human phase I trial (EudraCT 2022-003679-40)."

First-in-human • Journal • 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

Phase I Clinical Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single Doses of IM-250 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=18 | Completed | Sponsor: Innovative Molecules GmbH | Recruiting ➔ Completed | Trial completion date: Aug 2024 ➔ May 2024 | Trial primary completion date: May 2024 ➔ Jan 2024

Trial completion • Trial completion date • Trial primary completion date • Herpes Simplex

Helicase-primase inhibitors for the treatment of herpes simplex virus infections - patent evaluation of WO2023/225162 from gilead sciences inc. (PubMed, Expert Opin Ther Pat) - "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 (HPIs)...The asset was contributed to Assembly Biosciences, where it is under development as ABI-1179 at the investigational new drug (IND) enabling stage for high-recurrence genital herpes. A structure proposal for indolinoyl derivative ABI-1179 is presented, showing its potential opportunities and limitations compared to other HPIs."

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

Phase I Clinical Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single Doses of IM-250 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Innovative Molecules GmbH | Terminated ➔ Recruiting | N=18 ➔ 24 | Trial completion date: May 2024 ➔ Aug 2024

Enrollment change • Enrollment open • Trial completion date • Herpes Simplex

Phase I Clinical Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single Doses of IM-250 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=18 | Terminated | Sponsor: Innovative Molecules GmbH | Trial completion date: Aug 2024 ➔ May 2024 | Recruiting ➔ Terminated | Trial primary completion date: Jan 2024 ➔ May 2024; Three subsequent cohorts completed. Dose saturation almost achieved.

Trial completion date • Trial primary completion date • Trial termination • Herpes Simplex