Ovid Therapeutics announces publication of studies of OV350

Ovid Therapeutics announced the publication of multiple preclinical studies of OV350 in Cell Reports Medicine. The preclinical studies indicate that OV350 directly activates the potassium chloride cotransporter isoform 2 target, known as KCC2, and suggest that OV350 confers therapeutic efficacy in resistant epilepsy models and may offer a neuroprotective benefit. "These findings provide us with increased confidence that our unique program of KCC2 activators directly bind to the target and, as a result, may deliver significant seizure reduction in treatment-resistant epilepsies, such as status epilepticus. We continue to further characterize our KCC2 activator compounds across several modes of delivery and explore them in models of epilepsies and other conditions associated with neuronal excitation," said Manoj Malhotra, Chief Medical Officer of Ovid Therapeutics. The paper presents data characterizing the mechanistic target engagement of OV350 and evaluates its potential in several translatable, animal seizure models. Mechanistic Engagement Findings. Several mechanistic studies articulated in Cell Reports Medicine suggest that OV350: Directly binds to the KCC2 co-transporter with high affinity and potentiates KCC2 activity without modifying its plasma membrane accumulation or key regulatory phosphorylation sites. Is brain-penetrant and does not show overt effects on behavior in mice. Increases KCC2 activity in neurons and efficiently reduces Cl- accumulation to moderate hyperexcitability. Potential Anticonvulsant & Neuroprotective Properties: Data published from multiple animal models suggest that OV350, at a consistent studied dose, provided significant anticonvulsant properties. Additionally, when OV350 was prophylactically administered, it appeared to prevent seizures in a mouse model. Results were reported from two validated pharmacological screening models: the convulsant pentylenetetrazole model and the kainate-resistant status epilepticus model. These findings suggest OV350: Terminated ongoing resistant status epilepticus and restored the efficacy of benzodiazepines. Prevents the development of benzodiazepine resistant status epilepticus. Reduces neuronal cell injury and death following status epilepticus.