Assembly Biosciences, Inc. announced new preclinical data from its investigational herpes simplex virus (HSV) portfolio featured in three presentations at the International Herpesvirus Workshop (IHW), taking place July 13-17, 2024, in Portland, Ore. Approximately 50% of individuals with initial symptomatic genital herpes infection have three or more recurrences per year, including over four million people in the United States and France, Germany, Italy and Spain (collectively, the EU4), and the United Kingdom. While genital herpes can be caused by either HSV type 1 (HSV-1) or HSV type 2 (HSV-2), recurrences are more likely to be experienced by individuals infected by HSV-2. The current standard of care for recurrent genital herpes are nucleoside analogs; however, these are only partially effective in preventing recurrences.

Assembly Bio?s HSV antiviral candidates target the HSV helicase-primase complex, an essential HSV enzyme complex with no host equivalent, and are designed for long-acting administration. A poster entitled ?The Helicase-Primase Inhibitor ABI-5366 Is a Novel, Potent, Long-Acting Inhibitor for the Treatment of Recurrent Genital Herpes? highlights preclinical data that supported ABI-5366?s entry into Phase 1 clinical evaluation.

Results demonstrated that ABI-5366 showed low nanomolar activity against both HSV-1 and HSV-2, including broad activity against HSV clinical isolates, and specificity for HSV. ABI-5366 was shown to be generally non-toxic across a variety of cell types with no off-target effects observed in vitro or in vivo, including no activity against carbonic anhydrase esterases. Further, a favorable in vivo safety profile of ABI-5366 was observed in 28-day oral toxicity studies in two species, and pharmacokinetic (PK) studies evaluating ABI-5366 when administered orally or intramuscularly demonstrated long-acting potential for this compound.

The Phase 1a/b study for ABI-5366 was initiated in May 2024 and is currently enrolling; interim Phase 1a data are expected in Third Quarter 2024 and interim Phase 1b data are expected in the first half of 2025. Additionally, an oral and poster presentation entitled ?Preclinical Characterization of ABI-1179, a Potent Helicase Primase Inhibitor for the Treatment of Recurrent Genital Herpes? features preclinical data from ABI-1179, a structurally distinct, long-acting helicase-primase inhibitor candidate, licensed from Gilead Sciences, Inc. (Gilead) under the collaboration between Assembly Bio and Gilead.

ABI-1179 has demonstrated low nanomolar activity across HSV-1 and HSV-2 lab strains and clinical isolates, including acyclovir-resistant isolates. In resistance selection studies, ABI-1179 displayed a higher barrier to resistance development than acyclovir. Furthermore, ABI-1179 demonstrated antiviral activity against some HSV-2 strains harboring mutations known to confer resistance to other helicase-primase inhibitors.

In a preclinical study, ABI-1179 demonstrated a favorable PK profile that supports the evaluation of once-weekly oral dosing. Further, in a preclinical model of recurrent HSV infection, ABI-1179 significantly reduced the development of recurrent lesions. Assembly Bio expects to initiate a Phase 1a/b first-in-human study of ABI-1179 by the end of 2024.