Ovid Therapeutics and Graviton Bioscience Reveal Phase 1 Data on OV888/GV101 for Cerebral Cavernous Malformations

Ovid Therapeutics Inc., a biopharmaceutical company focused on rare epilepsies and brain conditions, and Graviton Bioscience Corporation, a clinical-stage biotechnology firm developing innovative compounds, have announced promising results from their Phase 1 study of the OV888/GV101 capsule. This study, involving healthy volunteers, aimed to assess the safety, tolerability, and pharmacokinetic profile of multiple ascending doses of the OV888/GV101 capsule.

The study was structured as a single-center, double-blind, randomized, placebo-controlled, multiple ascending dose (MAD) trial. Participants received either the OV888/GV101 capsule or a placebo once daily over seven days at varying doses of 100 mg, 200 mg, 400 mg, and 600 mg. The capsule met its safety and tolerability objectives, with no serious adverse events reported. The adverse events that did occur were mild and resolved without significant impact. Headaches were the most common side effect, affecting 23% of participants, but all cases were transient and resolved within the study period. Only one participant discontinued the study due to mild headache and nausea, which also resolved after stopping the medication.

The OV888/GV101 capsule demonstrated biological activity in humans, showing a dose-dependent decrease in the secretion of proinflammatory cytokines IL-17 and IL-21, which are markers of selective ROCK2 inhibition. This suggests that the capsule is effective at the target clinical dose and elicits a pharmacodynamic response.

The pharmacokinetic data supported the potential for once-daily dosing, with a dose-dependent increase in both Cmax and AUC0-24 up to the 400 mg target dose. The average half-life of approximately 12 hours further supports this dosing regimen. Laboratory results showed some asymptomatic findings, such as increases in total bilirubin and creatine phosphokinase levels, but these were clinically insignificant and resolved during the study period.

The promising Phase 1 results have paved the way for a Phase 2 proof-of-concept study in individuals with cerebral cavernous malformations (CCM), expected to begin in the second half of 2024. Currently, there are no FDA-approved pharmacological treatments for CCM, a condition characterized by clusters of abnormal blood vessels in the brain that can cause bleeding, headaches, seizures, and other neurological symptoms. Surgical resection is the only recommended treatment, but it is not always feasible depending on the lesion's location.

OV888/GV101 capsule is a highly selective inhibitor of ROCK2, crucial for vascular endothelial function. Abnormal activation of the ROCK2 pathway is a key component of CCM pathogenesis. Preclinical studies have shown that the OV888/GV101 capsule is blood-brain-barrier penetrant and highly selective for ROCK2, indicating its potential as a first-in-class oral therapy for CCM and other rare CNS diseases.

Graviton Bioscience Corporation, led by Dr. Samuel Waksal, is focused on developing best-in-class therapeutics for CNS, autoimmune, fibrotic, and other serious diseases where ROCK2 and other therapeutic compounds play a significant role. Dr. Waksal, the founder of Kadmon Pharmaceuticals and ImClone Systems, brings extensive experience in the biotechnology sector.

Ovid Therapeutics, based in New York, is dedicated to improving the lives of people affected by rare epilepsies and brain conditions. Alongside OV888/GV101, Ovid is developing other promising candidates such as OV329, a GABA-aminotransferase inhibitor for treatment-resistant seizures, and OV350, a KCC2 transporter activator for epilepsies and psychiatric conditions. These initiatives reflect Ovid's commitment to advancing novel, targeted therapies for neurological diseases.