Ovid Therapeutics (OVID) Status update summary

Vision and Strategic Opportunity

• Focused on pioneering a new class of CNS medicines by targeting KCC2, a master regulator of neural excitation/inhibition balance, with OV4071 positioned as a pipeline-in-a-product for broad psychotic disorders.

• Pipeline includes highly specific small molecules for neural hyperexcitability, with additional undisclosed KCC2 activators in preclinical development.

• OV4071 is positioned for development in psychosis, schizophrenia, Parkinson’s disease psychosis, and Lewy body dementia, with multiple clinical and regulatory milestones anticipated through 2026–2027.

• The approach leverages creative translational biomarker strategies for efficient proof-of-concept and rapid clinical translation.

• KCC2 activation is seen as a transformative opportunity, potentially analogous to PD-1 in oncology, with applications in multiple CNS disorders.

Mechanistic and Preclinical Evidence

• KCC2 is exclusively expressed in the CNS, regulating neural network hyperexcitability and sitting upstream of many approved psychosis drugs.

• Direct activation of KCC2 restores GABAergic inhibition and rebalances hyperexcitability, addressing core pathophysiology in psychotic disorders.

• Over 25 pharmacodynamic models show consistent restoration of excitatory/inhibitory balance and improvement in cognitive and behavioral deficits with KCC2 activators.

• OV4071 demonstrates rapid, dose-dependent antipsychotic effects, restoring social interaction and cognitive function in preclinical models, with activity equal to or surpassing current antipsychotics and no sedation or catalepsy.

Translational and Clinical Development Strategy

• Biomarker-driven approach uses quantitative EEG and other electrophysiological markers to bridge preclinical and clinical findings, establishing mechanistic continuity.

• Phase 1 studies in healthy volunteers show good safety, predicted PK, and qEEG biomarker shifts consistent with central KCC2 activity.

• Phase I studies include safety, tolerability, and biomarker assessments, with a ketamine challenge to model disease biology.

• Phase II proof-of-concept studies in schizophrenia, Parkinson’s disease psychosis, and Lewy body dementia are planned, focusing on PANSS and SAPS endpoints, with additional Phase 1b PoC studies planned for 2026–2027.

• The program aims to de-risk development by extracting maximal information from early biomarker and electrophysiology data.