OV888

OV888 & ROCK2 platform

overview

Ovid entered a collaboration with Graviton Biosciences on May 1, 2023. Together, the companies intend to develop OV888, previously known as GV101, and a potential portfolio of selective ROCK2 inhibitors for the treatment of a broad range of neurological conditions, including cerebral cavernous malformations.

mechanism of action

Rho-associated coiled-coil containing protein kinase 1 and 2 (ROCK1/2) are kinases with isoform differences in tissue distribution. Specifically, ROCK2 is expressed abundantly in skeletal muscles and in the brain and is believed to primarily function to regulate intracellular cytoskeletal organization. Evidence suggests that the ROCK2 signaling pathway may be hyperactivated in multiple neurological diseases, including disorders involving vascular structures and nerve myelination diseases that can result in seizures, spasms and a variety of symptoms. Despite this link, there has been limited clinical development of ROCK2 inhibitors due to challenges penetrating the blood-brain barrier (BBB) and the inherent challenge of avoiding inhibition of ROCK1, which can drive unwanted side effects.

development

The lead compound, OV888 is a highly selective and potent ROCK2 inhibitor. Preclinical studies to date have demonstrated a favorable toxicology profile.

OV888 has completed a Phase 1, placebo-controlled, randomized, double-blind single ascending dose study in healthy volunteers and is currently in a double-blind multiple ascending dose study.

potential indications

Initial clinical development is anticipated to address cerebral cavernous malformations, for which there is strong mechanistic evidence for inhibiting ROCK2. See below to learn more about cerebral cavernous malformations.