Ovid Therapeutics Reports Positive Phase 1 Results for OV350 – A Breakthrough KCC2 Activator

On December 18, 2025, Ovid Therapeutics Inc. (Nasdaq: OVID), a pioneering biopharmaceutical company focused on developing small molecule medicines for brain disorders, announced promising results from its Phase 1 study of OV350, the first-ever direct activator of the potassium-chloride cotransporter 2 (KCC2) tested in humans. The study effectively met its primary objectives, including evaluations of safety, tolerability, and pharmacokinetics. These findings pave the way for further development of Ovid's oral KCC2 activators.

Key Findings and Safety Profile of OV350

The Phase 1 trial was an exploratory, randomized, placebo-controlled study involving 16 healthy participants, administered with 50 mg and 100 mg doses of OV350 via intravenous infusion. Key outcomes included:

• Doses achieved expected pharmacologically active concentrations.
• No significant treatment-related laboratory findings or serious adverse events (SAEs) were reported.
• The most frequently observed adverse event was headache, along with some instances of nausea and vomiting, attributed to off-target effects.
• Pharmacokinetic data aligned with predictions, informing future dosing strategies.
• Quantitative electroencephalography (qEEG) results suggested central activity consistent with KCC2 modulation.

These results support the advancement of Ovid’s KCC2 portfolio, particularly leading to continued development of OV4071, the first oral direct KCC2 activator expected to achieve regulatory submission for a Phase 1/1b clinical trial by Q1 2026.

Advancements in Ovid's KCC2 Portfolio

Moving forward, Ovid plans to accelerate its development of oral formulations, including OV4071 and OV4041. Meg Alexander, President and COO of Ovid Therapeutics, stated, “The results from OV350 give us confidence that this new mechanistic class is suitable for further development and reinforces our earlier decision to invest in additional direct activator molecules.”

Ovid’s KCC2 direct activators, including OV4071, are aimed at addressing neurological conditions like Parkinson’s disease and Lewy body dementia, where there is significant unmet medical need.

Understanding KCC2 and Its Importance

KCC2, a neuron-specific chloride transporter, plays a critical role in maintaining inhibitory balance within the brain. Its direct activation represents a differentiated treatment approach for serious neurological and neuropsychiatric conditions linked to +neural hyperexcitability. Ovid aims to establish a first-in-class franchise focusing on restoring this balance to provide therapeutic benefits across various disorders.

About Ovid Therapeutics

Ovid Therapeutics Inc., based in New York, specializes in developing small molecule therapeutics targeting brain conditions associated with excess neural excitability. The company also has several promising candidates under development, including OV329, a potential therapy for treatment-resistant seizures. Ovid is committed to advancing its innovative pipeline, combining its expertise in neuroscience with a dedication to improving patient outcomes in neurological and neuropsychiatric disorders.

Looking Ahead

The results from this Phase 1 study of OV350 will contribute to Ovid’s ongoing efforts to develop next-generation KCC2 activators, aiming for both oral and injectable formulations. This innovative approach could lead to significant advancements in the treatment of various central nervous system disorders, further establishing OVID as a key player in biopharmaceutical innovation.

For further details on Ovid Therapeutics and its ongoing research programs, visit www.ovidrx.com.