OV350 / Ovid Therapeutics, AstraZeneca - LARVOL DELTA

Enhancing KCC2 Function with OV350 Reverses Neurological and Behavioral Phenotypes in Female MeCP2+/− Mice (Neuroscience 2026) - "Together, these findings demonstrate that impaired KCC2 phosphorylation contributes to network hyperexcitability and behavioral deficits in Rett syndrome. Thus, targeting KCC2 function may be a promising therapeutic approach for Rett syndrome and other neurodevelopmental disorders."

Preclinical • CNS Disorders • Epilepsy • Mental Retardation • Movement Disorders

Activation of KCC2 as a novel strategy for potential treatment of psychosis (APA 2026) - "For validation, compounds were tested in murine models of psychosis using the psychotomimetics phencyclidine phosphate (PCP) and MK801... The SmartCube® revealed that OV350 has a signature robustly similar to atypical antipsychotics such as risperidone and clozapine... This study suggests that KCC2 activators can potentially treat psychotic symptoms through a novel mechanism of action. In addition to the suppression of psychotomimetic-induced hyperlocomotion with both OV350 and OV4071, lack of motor disturbance and alterations of the resting state qEEG pattern with OV350, together suggest that these compounds may target mechanisms distinct from those of current antipsychotics and represent a meaningful advance in the development of safer and more effective treatments for psychotic disorders, warranting further study. This study was supported by Ovid Therapeutics, Inc."

CNS Disorders • Metabolic Disorders • Psychiatry

KCC2 activation during postnatal development alleviates long-term deficits in CDKL5-deficient mice. (PubMed, Exp Mol Med) - "Remarkably, when these mice were adults, the mice that received OV350 as pups had reduced seizure susceptibility and their cognitive and behavioral deficits were alleviated. These findings indicate that enhancing KCC2 function during a critical developmental window may be a promising therapeutic strategy for CDD and other developmental and epileptic encephalopathies."

Journal • Preclinical • CNS Disorders • Epilepsy • Genetic Disorders • CDKN1A

KCC2 Activation Reverses Neurophysiological and Behavioral Deficits in Female Rett Mice. (PubMed, bioRxiv) - "Deficits in KCC2 phosphorylation were also seen in MeCP2 +/- mice, consistent with reductions in its activity that were also ameliorated by OV350. Thus, KCC2 activation may be efficacious in limiting the impact of Rett syndrome and other neurodevelopmental disorders."

Journal • Preclinical • CNS Disorders • Developmental Disorders • Epilepsy • Mental Retardation • Movement Disorders • Psychiatry

An Ascending, Single and Multiple Dose(s), Double-Blind, Randomized, Placebo Controlled Study Assessing the Safety, Tolerability, and Pharmacokinetics of Intravenous OV350 in Healthy Male and Female Participants (ANZCTR) - P1 | N=72 | Recruiting | Sponsor: Ovid Therapeutics Australia Pty Ltd

New P1 trial • CNS Disorders • Movement Disorders • Parkinson's Disease

Ovid Therapeutics Reports Business Updates and Fourth Quarter and Full Year 2024 Financial Results (GlobeNewswire) - "...Anticipated milestones include: results for OV329 biomarker and safety data (Q3 2025); initiation of a Phase 2a patient study for OV329 in drug resistant epilepsies (Q1 2026); results from a first-in-human safety and exploratory biomarker study with OV350, our first KCC2 direct activator (Q4 2025); and initiation of human trials for the first oral KCC2 direct activator, OV4071 (Q2 2026)."

Biomarker • Clinical data • New P2a trial • New trial • Epilepsy

Activation of KCC2 during development alleviates cognitive, behavioral, and neural excitability in adult CDKL5-deficient mice. (PubMed, bioRxiv) - "Because KCC2 loss-of-function has been strongly correlated with excessive neuronal excitation, cognitive and behavioral impairments, we examined seizure susceptibility, spatial memory, and social interaction in adult Cdkl5 KO mice following once daily administration of the KCC2 activator (OV350), or vehicle, to infant Cdkl5 KO mice...In summary, this study demonstrates that enhancing KCC2 function may be a potential therapeutic target for CDD and other DEEs. However, early intervention during critical developmental windows is crucial for optimal outcomes."

Journal • Preclinical • CNS Disorders • Epilepsy • Genetic Disorders • CDKL5 • CDKN1A

Evaluation of Anticonvulsant Efficacy of the KCC2 Activator, OV350, in a Rat Model of Nerve Agent Poisoning (AES 2024) - "OV350 was evaluated as an adjunctive therapy to standard medical countermeasures (SMCs) atropine, 2-PAM, and midazolam. Methods were based on a model of nerve agent-induced BDZ-RSE that has been previously published [1]. These data suggest that the KCC2 activator, OV350, can act to terminate seizures, improve survival, and protect from the associated brain tissue damage following soman exposure plus SMCs."

Preclinical • CNS Disorders • Epilepsy

Potentiation of KCC2 Shows Neuroprotective and Anti-inflammatory Effects in Kainic Acid-induced Refractory Status Epilepticus Model (AES 2023) - "We have shown that a KCC2 activator, OV350, restores efficacy of BDZs in terminating ongoing SE and decreases the seizure-associated neuronal cell death in kainic acid-induced seizure mouse model... Utilizing cortical EEG recordings, we assessed the efficacy of diazepam (DZP) to terminate SE in KCC2 T906/1007A animals, in which KCC2 activity is enhanced... Our results provide evidence that potentiating KCC2 activity via pharmacological intervention or genetic manipulation is efficacious in terminating BDZ-resistant seizures and in limiting neuronal injury and inflammation."

CNS Disorders • Epilepsy • Inflammation

Activation of KCC2 by OV350 Reverses Diazepam Resistant Seizures in Cdkl5 KO Mice (AES 2023) - "The alteration in the phosphorylation of KCC2 in Cdkl5-KO mice (decreased S940, S1022 and increased T1007 phosphorylation) is consistent with described effects resulting from such changes: reduced KCC2 activity, seizures, and cognitive impairment. Treatment with OV350 significantly reduced seizure properties as measured in EEG recordings. OV350 treatment reversed resistance to diazepam and restored its ability to terminate seizure activity in Cdkl5-KO mice."

Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Epilepsy • Genetic Disorders • Sleep Disorder

Studies Published in Cell Reports Medicine Validate the Potential of Direct KCC2 Activation in Resistant Seizures (GlobeNewswire) - "OV350 shown to arrest benzodiazepine resistant seizures and limit subsequent neuronal injury in an animal model of status epilepticus...In this model, mice were administered kainate, a convulsant that induces status epilepticus-like seizures, which are typically resistant to benzodiazepines. These seizures are then monitored by electroencephalogram (EEG). Initially, 62% of mice exhibited insensitivity to diazepam, a common benzodiazepine, and continued to experience status epilepticus....In a separate kainate model, mice that had received pre-treatment of OV350, versus diazepam alone, exhibited delayed onset of the first seizure and spent less time experiencing seizure activity than mice that had received pre-treatment with the comparator vehicle and diazepam."

Preclinical • CNS Disorders • Epilepsy

Ovid Therapeutics to Present Data on Its Epilepsy Programs at American Epilepsy Society Annual Meeting (2022) (Yahoo Finance) - "Ovid Therapeutics Inc...announced that preclinical data supporting its OV329 and OV350 programs in epilepsy and treatment-resistant seizures will be presented at the 2022 American Epilepsy Society (AES) Annual Meeting, taking place December 2-6 in Nashville, Tennessee."

Preclinical • CNS Disorders • Epilepsy

Ovid Therapeutics Reports Third Quarter 2022 Financial Results and Corporate Highlights (Yahoo Finance) - "Ovid intends to initiate a Phase 1 trial in Q4 2022, following the FDA clearance of the Company's IND application for OV329....Ovid believes compounds in the library may be suitable for a range of formulations and administrations that would make it possible to pursue both chronic and acute epilepsies, as well as additional potential neurological indications in the future. Ovid continues to target filing an IND for OV350 in 2024....Takeda continues to enroll and execute two pivotal Phase 3 trials studying soticlestat for Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS). Takeda anticipates related regulatory filings in its fiscal year 2024."

Enrollment status • IND • NDA • New P1 trial • CNS Disorders • Epilepsy

Ovid Therapeutics to Present at the 21st Annual Needham Virtual Healthcare Conference (Yahoo Finance) - "Ovid Therapeutics Inc...announced that management will present at the 21st Annual Needham Virtual Healthcare Conference on Thursday, April 14, 2022, at 12:45 p.m. ET....Ovid management will also take part on a panel focused on trends in the epilepsy therapeutic market, which is available to Needham investors and conference attendees on Monday, April 11, 2022, at 11.45 a.m. ET."

Clinical • CNS Disorders • Epilepsy