Ovid Therapeutics Advances OV329 to Phase 2 Following Positive Safety Results in Drug-Resistant Epilepsy Program
Key Insights
Ovid Therapeutics' next-generation GABA-AT (search) inhibitor OV329 demonstrated strong target engagement and superior safety profile compared to vigabatrin in Phase 1 trials with 68 participants.
The company plans to initiate Phase 2a studies for drug-resistant focal onset seizures (search) in Q2 2026, supported by comprehensive ophthalmic evaluations showing no retinal toxicity.
Ovid secured $175 million in financing to advance its pipeline through 2028, including first-in-class KCC2 (search) direct activators for neuropsychiatric conditions.
Ovid Therapeutics announced positive Phase 1 results for OV329, a next-generation GABA-aminotransferase (GABA-AT (search)) inhibitor, demonstrating strong inhibitory activity and a potentially superior safety profile that supports advancement into Phase 2 patient studies for drug-resistant epilepsy (search). The company also secured significant financing and announced a leadership succession plan to support its expanding neurological pipeline.
Phase 1 Results Show Promise for Epilepsy Treatment
The Phase 1 clinical trial enrolled 68 participants, including 51 who received OV329 and 17 who received placebo across single and multiple ascending dose cohorts. The study utilized an expansive biomarker strategy to characterize OV329's potential target engagement and pharmacodynamic activity.
OV329 at 3 mg and 5 mg doses suppressed the GABA-AT (search) enzyme and delivered statistically significant inhibition in the brain as measured across multiple metrics on transcranial magnetic stimulation and magnetic resonance spectroscopy. The degree of OV329's cortical inhibition matched or exceeded levels of inhibition previously observed for therapeutic doses of the first-generation GABA-AT inhibitor vigabatrin in comparable healthy volunteer studies.
"The OV329 biomarker results, progress across our KCC2 (search) direct activator programs, and our recent financing reflect disciplined execution," said Dr. Jeremy M. Levin, current Chairman and CEO of Ovid Therapeutics.
Superior Safety Profile Addresses Key Limitation
Across all doses tested, OV329 was well tolerated with no treatment-related serious adverse events observed, and adverse events were generally mild and transient. Most notably, comprehensive ophthalmic evaluations showed no treatment-related ocular changes, contrasting with the known visual field defects and retinal changes historically associated with vigabatrin.
The ophthalmic safety assessments included best-corrected visual acuity, fundus photography, dilated indirect ophthalmoscopy, automated threshold perimetry, and optical coherence tomography. This outcome reinforces preclinical studies showing that OV329 does not accumulate in the retina like vigabatrin, potentially addressing a major limitation of current GABA-AT (search) inhibitor therapy.
Phase 2 Development Plans
Based on the favorable safety, tolerability, and pharmacodynamic profile observed in the Phase 1 study, Ovid plans to initiate a Phase 2a clinical study in Q2 2026 for the treatment of drug-resistant focal onset seizures (search). The company is currently seeking scientific advice with regulators across multiple regions.
Ovid is concurrently assessing the safety and tolerability of a 7 mg dose of OV329 for potential evaluation in patient studies, given the favorable tolerability profile observed for the 5 mg dose. The 7 mg cohort data, including safety, tolerability and pharmacokinetics, will be available before the initiation of the Phase 2a trial to help confirm dose selection.
Expanding KCC2 Portfolio Shows Progress
Ovid's first-in-class portfolio of small molecules that directly activate potassium-chloride cotransporter 2 (KCC2 (search)) continues to advance. KCC2 is a neuron-specific chloride transporter that maintains inhibitory balance in the brain and plays a central role in regulating neuronal excitability by enabling gamma-aminobutyric acid (GABA) to exert its inhibitory effect.
The company expects to report first-in-human data for OV350, an intravenous KCC2 (search) direct activator, in Q4 2025. Results from OV350 are intended to establish foundational safety for this new class of molecules and inform the continued development of future oral candidates.
OV4071 (search), the first oral KCC2 (search) direct activator, is anticipated to enter clinical studies in Q2 2026. The compound is being developed initially for psychosis associated with Parkinson's disease (search) and Lewy body dementia (search), representing areas of high unmet need with established regulatory pathways. The company is also exploring additional conditions including schizophrenia (search) and psychoses associated with other neurodegenerative conditions.
Financial Position and Leadership Transition
Ovid completed a private placement totaling up to $175 million in gross proceeds, including an initial closing of approximately $81 million. Combined with existing cash reserves of $25.6 million as of September 30, 2025, this financing is expected to fund operations and clinical pipeline development into the second half of 2028.
The company announced that Meg Alexander will assume the role of CEO effective January 1, 2026, while Dr. Jeremy M. Levin will transition to Executive Chairman of the Board. Alexander has served as President and Chief Operating Officer since joining Ovid in 2021.
"Ovid is at an important inflection point. We are within months of bringing OV329 into patient trials with drug-resistant epilepsies, reading out safety of the first-ever KCC2 (search) direct activator, and submitting the first-ever oral KCC2 direct activator for human studies," said Alexander.
The OV329 Phase 1 study results will be featured in a late-breaking poster session at the 2025 American Epilepsy Society annual meeting, occurring December 5-9, 2025 in Atlanta, Georgia.