OV329 Program & Clinical Development - OV329 is a next-generation GABA-aminotransferase inhibitor being developed for neuronal hyperexcitability and seizures[27] - Phase 1 topline results for OV329, including biomarker data, are expected in Q3 2025[20, 16] - A Phase 2a trial in patients with focal-onset seizures is planned to start in Q1 2026, with topline results expected in Q1 2027[20] - Phase 1 trial includes single ascending dose (SAD) and multiple ascending dose (MAD) cohorts, with a total of 64 participants (48 receiving active treatment)[90] Biomarker Strategy - The OV329 Phase 1 trial incorporates a comprehensive biomarker strategy using magnetic resonance spectroscopy (MRS), transcranial magnetic stimulation (TMS), and electroencephalogram (EEG) to assess target engagement and pharmacodynamic effects[43, 45] - MRS will measure GABA concentrations in the medial parietal lobe to validate target engagement[45] - TMS will assess cortical excitability and brain circuit function, with metrics like cortical silent period (CSP) and paired-pulse long-interval intracortical inhibition (LICI)[45] - EEG will measure brain waves linked to inhibitory (GABAergic) activity, focusing on high and low frequencies[45] - Targeted directional changes in TMS biomarkers are anticipated, with increases in CSP and LICI, consistent with the effects of therapeutic vigabatrin[74] Market Opportunity - The company estimates a >$1 billion market opportunity for OV329 in drug-resistant epilepsy (DRE), targeting 65,000 adults with focal onset seizures and a price of $16,000 per year[38] - There is a substantial opportunity within the developmental epileptic encephalopathies (DEE) segment, with a potential market of ~20,000 patients and an average price of $60,000 per year, representing a >$1 billion market[116] Safety & Tolerability - In the Phase 1 trial, no treatment-related adverse events (AEs) or serious adverse events (SAEs) were observed in 30 treated participants, with headache being the most common AE[95, 94] - Comprehensive ocular safety metrics in Phase 1 showed no vision or ocular findings associated with OV329 treatment[96] - Preclinical studies show OV329 does not accumulate in the retina, unlike vigabatrin, suggesting a differentiated safety profile[107, 109]