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Studies Published in Cell Reports Medicine Validate the Potential of Direct KCC2 Activation in Resistant Seizures
OV350 is the first reported compound that directly binds to and activates the KCC2 co-transporter, a target implicated in neuronal excitation, including
About this update from Ovid Therapeutics Inc.
[{"type":"text","content":"OV350 is the first reported compound that directly binds to and activates the KCC2 co-transporter, a target implicated in neuronal excitation, including epilepsiesTwo preclinical seizure models suggest that OV350 mitigates neuronal hyperexcitability by reducing intracellular chloride accumulationOV350 shown to arrest benzodiazepine resistant seizures and limit subsequent neuronal injury in an animal model of status epilepticus NEW YORK, March 08, 2023 (GLOBE NEWSWIRE) -- Ovid Therapeutics Inc. (NASDAQ: OVID), a biopharmaceutical company developing medicines designed to conquer epilepsies and meaningfully improve the lives of people affected by brain disorders, today 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. Publication of the data was led by Dr. Stephen Moss and a team at the Tufts Laboratory for Basic and Translational Neuroscience Research, as well as a team of researchers at AstraZeneca. Ovid in-licensed AstraZeneca’s portfolio of approximately 100 KCC2 activator compounds from AstraZeneca in January 2022, and continues to work with Dr. Moss related to the development of KCC2 activators and other small molecule antiseizure programs. 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 membr...