Ovid Therapeutics Inc. and Graviton Bioscience Corporation announced the results from their Phase 1 healthy volunteer study evaluating the safety, tolerability, and pharmacokinetic (PK) profile of multiple ascending doses of OV888/GV101 capsule. Ovid and Graviton Bioscience plan to progress to a Phase 2 clinical study in cerebral cavernous malformations (CCM) later this year. Summary of Phase 1 Topline Findings: The Phase 1 study was a single-center, double-blinded, randomized, placebo-controlled, multiple ascending dose (MAD) trial to evaluate the safety, tolerability, and PK profile of OV888/GV101 capsule in healthy adult volunteers.

OV888/GV101 capsule or placebo was administered once daily for seven days. The MAD cohorts evaluated doses of 100 mg, 200 mg, 400 mg, and 600 mg. OV888/GV101 capsule met the study?s primary safety and tolerability objectives and characterized its PK properties.

Well tolerated at all tested doses. There were no serious adverse events (SAEs) and no participants met the preset trial stopping criteria. All drug-associated clinical adverse events (AEs) were mild (Grade 1) and resolved.

The most commonly reported clinical AE was headache, which occurred in 23% of participants. All participants reporting headaches had transient cases, which resolved. One subject discontinued the study early due to mild headache and nausea, which resolved after study drug discontinuation.

Most clinical AEs resolved within 24 hours, all resolved within the study period. There were no AEs reported in the placebo cohort. Target engagement achieved.

There was a dose dependent decrease in proinflammatory cytokines IL-17 and IL-21 secretion by stimulated peripheral blood mononuclear cells. These decreases are markers of selective ROCK2 inhibition. These findings indicate that OV888/GV101 is biologically active in humans at the target clinical dose and elicits a pharmacodynamic response.

Exposure and half-life findings supportive of daily dosing. Topline data show a dose dependent increase in Cmax and AUC0-24 up to the 400 mg target dose. The average half-life is approximately 12 hours suggesting that OV888/GV101 capsule may be well suited for once daily dosing.

Laboratory results. In the study period, there were two asymptomatic laboratory findings rated Grade 2 or higher, which occurred in at least 5% of treated subjects relative to placebo. Increases in total bilirubin without direct hyperbilirubinemia were reported in 30% of participants.

These elevations were clinically insignificant and are consistent with the understood effect of ROCK2 inhibition on UGT1A1 enzyme. Importantly, no concurrent liver enzyme elevations were observed. Creatine phosphokinase elevations without muscle pain or weakness were reported in 7% of participants.

There were no reported related clinical impacts for either laboratory finding, and all participants normalized during the study period. Ovid and Graviton expect to initiate a Phase 2 proof-of-concept study in people living with CCMs in the second half of 2024. Additionally, under the collaboration agreement between Ovid and Graviton, the parties have agreed to develop an intravenous formulation of OV888/GV101 for undisclosed neurological indications.