8-K: Ovid Therapeutics and Graviton Bioscience Announce Positive Topline Data for Potential CCM Treatment

Ovid Therapeutics and Graviton Bioscience reported positive topline results from a Phase 1 trial of OV888/GV101 capsule, a potential first-in-class therapy for cerebral cavernous malformations (CCM).

Summary

• Ovid Therapeutics and Graviton Bioscience have announced positive results from a Phase 1 clinical trial for OV888/GV101 capsule.
• The study evaluated the safety, tolerability, and pharmacokinetic profile of the drug in healthy volunteers.
• The primary objective of the study was met, demonstrating a favorable safety and tolerability profile with no serious adverse events.
• Secondary endpoints were also achieved, indicating that the target pharmacokinetic profile was reached at the targeted clinical dose, supporting once-daily dosing.
• The drug showed biological activity in participants and elicited dose-dependent pharmacodynamic effects within the planned therapeutic dose range.
• A Phase 2 study for the treatment of cerebral cavernous malformations is expected to begin in the second half of 2024.
• The Phase 1 trial was a single-center, double-blinded, randomized, placebo-controlled, multiple ascending dose trial.
• Doses of 100 mg, 200 mg, 400 mg, and 600 mg were evaluated, with the 400mg dose being the target dose.
• The most common adverse event was headache, reported in 23% of participants, which were transient and resolved.
• There was a dose-dependent decrease in pro-inflammatory cytokines, indicating selective ROCK2 inhibition.
• The average half-life of the drug is approximately 12 hours, supporting once-daily dosing.
• Increases in total bilirubin were reported in 30% of participants, but were clinically insignificant.
• Creatine phosphokinase elevations were reported in 7% of participants, with no related clinical impacts.

Sentiment

Score: 8

Explanation: The document presents positive results from a Phase 1 trial, with a clear path to Phase 2. The drug shows promise as a potential first-in-class treatment for a disease with no current pharmacological options. The sentiment is very positive, with some minor adverse events that are not concerning.

Positives

• The drug demonstrated a favorable safety and tolerability profile in the Phase 1 trial.
• The target pharmacokinetic profile was achieved, supporting once-daily dosing.
• OV888/GV101 capsule showed biological activity and elicited a pharmacodynamic response.
• The drug has the potential to be a first-in-class oral treatment for cerebral cavernous malformations.
• The study showed a dose-dependent decrease in pro-inflammatory cytokines, indicating selective ROCK2 inhibition.
• The average half-life of approximately 12 hours supports once-daily dosing.
• All adverse events were mild and resolved within the study period.

Negatives

• Headache was the most commonly reported adverse event, occurring in 23% of participants.
• One participant discontinued the study early due to mild headache and nausea.
• Increases in total bilirubin were reported in 30% of participants, although these were clinically insignificant.
• Creatine phosphokinase elevations were reported in 7% of participants, with no related clinical impacts.

Risks

• The Phase 2 study is still subject to the inherent risks of clinical development.
• The drug's efficacy in treating cerebral cavernous malformations is yet to be proven in a larger patient population.
• There are risks associated with the regulatory approval process.
• The company may not be able to realize the intended benefits of its technology or business strategy.
• There are risks related to the company's ability to identify business development targets or strategic partners.

Future Outlook

Ovid and Graviton plan to initiate a Phase 2 proof-of-concept study in people living with CCMs in the second half of 2024. They also plan to develop an intravenous formulation of OV888/GV101 for undisclosed neurological indications.

Management Comments

• Dr. Jeremy Levin, Chairman and CEO of Ovid Therapeutics, stated that they hope to bring an oral, potentially first-in-class, highly selective ROCK2 inhibitor to the CCM community.
• Dr. Levin also mentioned that the mechanism of action has broad potential applications in multiple additional neurovascular and neuro-inflammatory conditions.
• Samuel Waksal, CEO and founder of Graviton, said that the data reinforces their conviction that OV888/GV101 capsule has the potential to become the first oral treatment for CCM.
• Dr. Waksal also stated that they believe the highly selective inhibition of ROCK2 could have a three-pronged effect in CCM.

Industry Context

This announcement is significant as there are currently no FDA-approved pharmacological treatments for cerebral cavernous malformations, making OV888/GV101 a potential first-in-class therapy. The standard of care is often watchful waiting or high-risk brain surgery, highlighting the unmet need for effective drug treatments.

Comparison to Industry Standards

• The successful completion of a Phase 1 trial with a favorable safety profile is a positive step for a drug targeting a rare disease like CCM.
• The achievement of the target pharmacokinetic profile and the demonstration of biological activity are encouraging signs for the potential efficacy of OV888/GV101.
• Compared to other neurological drug development programs, the rapid progression to a Phase 2 study is a positive indicator of the drug's potential.
• The lack of serious adverse events and the mild nature of reported adverse events are favorable compared to some other drug trials in the neurological space.
• The focus on a highly selective ROCK2 inhibitor is a novel approach compared to other treatments for CCM, which often involve surgery or watchful waiting.

Stakeholder Impact

• Shareholders may view the positive trial results as a positive development for the company's pipeline.
• Patients with cerebral cavernous malformations may benefit from a potential new treatment option.
• Employees of Ovid and Graviton may be motivated by the progress of the drug development program.
• The collaboration between Ovid and Graviton may strengthen their respective positions in the pharmaceutical industry.

Next Steps

• Initiation of a Phase 2 proof-of-concept study in people living with CCMs in the second half of 2024.
• Development of an intravenous formulation of OV888/GV101 for undisclosed neurological indications.

Key Dates

Keywords

Cerebral Cavernous Malformations, OV888/GV101, ROCK2 Inhibitor, Phase 1 Clinical Trial, Ovid Therapeutics, Graviton Bioscience, Pharmacokinetics, Pharmacodynamics, Neurology, Rare Diseases