OV888 & ROCK2 platform
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.
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.
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.
- Cerebral cavernous malformations are one of the most common intracranial vascular malformation in humans, presenting as mulberry-shaped abnormal blood vessels with thin, leaky walls located in the brain and or spinal cord.
- Cerebral cavernous malformations affect approximately 1:250 individuals (Flemming, 2017).
- At diagnosis, the majority of patients present symptomatically with hemorrhage, focal neurologic deficit and/or seizures.
Reference: 1. Flemming KD et al. Population-based prevalence of cerebral cavernous malformations in older adults: Mayo Clinic Study of Aging. JAMA neurology. 2017