OV329 / Ovid Therapeutics - LARVOL DELTA

A Follow-on, Ascending, Single and Multiple Dose(s), Double-Blind, Randomized, Placebo Controlled Study Assessing the Safety, Tolerability, and Pharmacokinetics of OV329 in Healthy Male and Female Participants (ANZCTR) - P1 | N=32 | Not yet recruiting | Sponsor: Ovid Therapeutics Australia Pty Ltd

New P1 trial • CNS Disorders • Epilepsy

OV329, a Potent Next Generation GABA-AT Inhibitor, is Well-tolerated and Produces GABA-ergic Cortical Inhibition in a Phase 1 SAD/MAD Study in Healthy Volunteers (AES 2025) - "Exploratory biomarkers assessed potential PD effects, including transcranial magnetic stimulation (TMS) metrics that were previously used to study a 1st-generation GABA-AT inhibitor, vigabatrin (VGB). OV329 is safe and well tolerated across the tested dose range. TMS measures indicate, like VGB, OV329 augments GABA- mediated TMS measures of cortical inhibition, and is a potential anti-convulsant candidate for patients with epilepsy supporting further clinical studies"

Clinical • Late-breaking abstract • P1 data • CNS Disorders • Epilepsy • Ophthalmology

An ascending, single and multiple dose(s), double-blind, randomized, placebo controlled study assessing the safety, tolerability, and pharmacokinetics of ov329 in healthy male and female participants (ANZCTR) - P1 | N=68 | Completed | Sponsor: Ovid Therapeutics Australia Pty Ltd | Recruiting ➔ Completed

Trial completion • CNS Disorders • Epilepsy

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

OV329, a Potent GABA-AT Inhibitor, Lacks Retinal Accumulation – a Comparative Pharmacokinetic Study in Mouse with Vigabatrin (AES 2024) - "Collectively, these data suggest that while VGB preferentially accumulates in retina, OV329 does not tend to accumulate either in eyeball or in retina at a dose that is deemed efficacious in rodents and the absence of OV329 in retina is likely not due to the limit of detection. However, it remains to be seen whether preferential retinal accumulation of VGB directly correlates with the adverse ocular effect and warrants further investigation."

PK/PD data • Preclinical • CNS Disorders • Epilepsy

Comparing the Effects of OV329 and Vigabatrin on GABA-AT Activity, and the Efficacy of Phasic and Tonic Inhibition (AES 2024) - "Results from this study suggest GABA-AT inhibition is a mechanism by which both phasic and tonic inhibition can be altered. Interestingly, we observed acute enhancement of tonic inhibition from vigabatrin at concentrations lower than our calculated IC50, suggesting there may be some non-GABA-AT based mechanism by which vigabatrin may be acutely acting. In contrast, OV329 shaped phasic and tonic GABA signaling only at concentrations higher than our calculated IC50."

Clinical • CNS Disorders • Epilepsy

OV329 Rapidly Inhibits GABA-AT, Elevates Brain GABA Levels and Leads to Seizure Suppression Following IV Administration in the Rat Lithium-pilocarpine Model of Status Epilepticus (AES 2024) - "Collectively, these data demonstrate that IV administration of OV329 resulted in higher exposure of OV329 in the brain with decreased GABA-AT activity which resulted in elevated levels of GABA in the brain. Finally, the IV administration of OV329 suppressed the duration of SE in the rat pilocarpine model of SE."

Preclinical • CNS Disorders • Epilepsy

eNeuro Publishes Findings on the Anti-Convulsant Properties of OV329 and Its Potential Effectiveness in Treatment-Resistant Seizures (GlobeNewswire) - "Ovid Therapeutics Inc...announced that eNeuro, a peer-reviewed, open-access journal from the Society for Neuroscience published several preclinical studies validating OV329’s mechanism of action and anti-convulsant properties....Mice treated with OV329 at 5 mg/kg every 24 hours for six days showed significantly reduced GABA-AT activity in the brain to 62.6 ± 4.4% of control (vehicle: 100.0 ± 2.7%; n=6 mice per experimental group; two tailed unpaired t-test). In parallel, treatment with OV329 significantly increased GABA levels to 134.0 ± 7.2% of control (vehicle: 100.0 ± 5.9%; n=6 mice per group; two-tailed unpaired t-test) as measured using liquid chromatography coupled with mass spectroscopy."

Preclinical • CNS Disorders

An ascending, single and multiple dose(s), double-blind, randomized, placebo controlled study assessing the safety, tolerability, and pharmacokinetics of ov329 in healthy male and female participants (ANZCTR) - P1 | N=56 | Recruiting | Sponsor: Ovid Therapeutics Australia Pty Ltd | Not yet recruiting ➔ Recruiting | Initiation date: Mar 2024

Enrollment open • Trial initiation date • CNS Disorders • Epilepsy

Sustained inhibition of GABA-AT by OV329 enhances neuronal inhibition and prevents development of benzodiazepine refractory seizures. (PubMed, eNeuro) - "Vigabatrin, a low affinity GABA-AT inhibitor, exhibits anticonvulsant efficacy but its use is limited due to cumulative ocular toxicity. In vivo application of OV329 exhibited enhanced tonic GABA signaling in mice at the synaptic level in the hippocampus, and at the network level reduced seizure severity and the development of benzodiazepine refractory seizures. This suggests OV329 may be of clinical use in the treatment of seizure disorders."

Journal • CNS Disorders • Epilepsy

An ascending, single and multiple dose(s), double-blind, randomized, placebo controlled study assessing the safety, tolerability, and pharmacokinetics of ov329 in healthy male and female participants (ANZCTR) - P1 | N=56 | Not yet recruiting | Sponsor: Ovid Therapeutics Australia Pty Ltd

New P1 trial • CNS Disorders • Epilepsy

Low, Repeat Dosing of OV329 Enhances GABA-AT Inhibition in Rodent Brain - Relationship Between Pharmacokinetic (PK) and Pharmacodynamic (PD) Effects (AES 2023) - "OV329 is a clinical stage compound that is a highly potent, GABA-AT inhibitor, a mechanism similar to that of vigabatrin (VGB), that holds the potential to be the best-in-class antiepileptic drug with this mechanism. This data demonstrates that OV329 inhibits the activity of GABA-AT in brain, and a significant level of GABA-AT inhibition with a concomitant change in GABA level can be achieved by repeat low, dose administration of OV329. Future studies are warranted to gain further insights on the inactivation mechanism of GABA-AT by OV329. Finally, low and multiple doses of OV329 may be a viable strategy for treating patients, which also may help avoid potential adverse effects without compromising efficacy."

PK/PD data • Preclinical • CNS Disorders • Epilepsy

Evaluation of OV329, a Next-Generation GABA-AT Inhibitor, in the Intra-Amygdala Kainate Model of Mesial Temporal Lobe Epilepsy (AES 2023) - "Results from studies in the IAK model suggest OV329 has potential antiepileptogenic activity following a single dose of 40 mg/kg as far out as nine weeks after treatment. In a previously executed IHK model of MTLE, OV329 was effective at reducing seizures following repeated, low dosing (3.0 mg/kg/day) over eight days. Therefore, evaluating a repeat dosing strategy to control the generation of seizures in the IAK model may lead to a meaningful outcome."

CNS Disorders • Epilepsy

Blocking of GABA-AT Activity by OV329 Selectively Alters Tonic and Phasic Inhibition in Dentate Gyrus Granule Cells (AES 2023) - "Funding: Ovid Therapeutics and NIH/NINDS (NS108378, NS111064, NS111338) Rationale: OV329 is a highly potent, clinical stage GABA-amino transferase (GABA-AT) inhibitor, that holds the potential to be the best-in-class antiepileptic drug with a mechanism of action similar to that of vigabatrin. Results from this study suggest inhibition of GABA-AT is a powerful tool by which both phasic and tonic inhibition can be modulated. Further, these data suggest that the effects on phasic and tonic inhibition are dependent on the extent of GABA-AT inhibition. Finally, repeated administration of OV329 led to robust DGGC tonic currents in vivo, likely due to increased extracellular GABA levels."

CNS Disorders • Epilepsy

Ovid Therapeutics Dosed Healthy Volunteers with OV329 in Phase 1 Trial (GlobeNewswire) - "Ovid Therapeutics Inc...dosed healthy volunteers with OV329 in late December 2022, as part of a Phase 1 study. The Company is conducting the study to evaluate the safety and target engagement associated with single and repeated doses of OV329....Ovid expects to enroll more than 60 individuals in this trial and anticipates final results in the first half of 2024."

Enrollment status • P1 data • Trial status • 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

OV329, a Next-generation GABA-AT Inhibitor, Suppresses Hpds Following Repeat Dosing in a Mouse Model of Mesial Temporal Lobe Epilepsy (AES 2022) - "Administration of OV329, a highly potent GABA-AT inhibitor, leads to increased levels of GABA via a mechanism similar to that of vigabatrin (VGB). The once-daily 3 mg/kg dose of OV329 administered for 8 days significantly reduced the number of HPDs by day 4 with maximum reduction at day 8 compared to the baseline in the MTLE mouse model (70 ± 9% inhibition at day 8; p < 0.05). Changes in baseline ictal duration were observed following 3 mg/kg OV329 treatment, and these persisted for 7 days following the last administration. No effect was observed with repeat administration of either the 1.0 or 0.3 mg/kg dose."

Preclinical • CNS Disorders • Epilepsy • Immunology

Evaluation of OV329, a Next-generation GABA-AT Inhibitor in a Series of Pharmaco-resistant Seizure Models Through the NINDS Epilepsy Therapy Screening Program (AES 2022) - "Administration of a highly potent GABA-AT inhibitor, OV329, is proposed to increase levels of GABA within the CNS through a mechanism of action similar to that of vigabatrin (VGB). Seizures induced in acute models (6 Hz and MES) were not mitigated by OV329 pretreatment at the doses tested. However, OV329 demonstrated efficacy in the subacute models of epileptogenesis (CKM and MTLE). In these, a single, high dose of OV329 produced near complete protection from seizure activity."

Anesthesia • CNS Disorders • Epilepsy • Immunology

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 Reports Second Quarter 2022 Financial Results and Corporate Highlights (GlobeNewswire) - "Ovid presented preclinical data that will support the IND submission for OV329 in the second half 2022. Data show that OV329 demonstrated robust anti-seizure activity in multiple preclinical seizure and epilepsy models, including treatment-resistant seizures. Ovid believes OV329 may be a potent, next-generation GABA-AT inhibitor with an improved ocular safety profile and therapeutic index compared to other therapies in the class. Ovid plans to submit an IND and initiate a Phase 1 trial in the second half 2022."

IND • New P1 trial • CNS Disorders • Epilepsy

Ovid Therapeutics Presents Preclinical Data on OV329 at the Epilepsy Foundation Pipeline Conference (Yahoo Finance) - "Ovid Therapeutics Inc...presented data at the 2022 Epilepsy Foundation Pipeline Conference. New preclinical data support the robust anti-seizure activity of OV329, a next-generation GABA-aminotransferase (GABA-AT) inhibitor in development for rare adult and pediatric epilepsies....'We plan to advance an IND submission for OV329 to the FDA and expect to initiate clinical studies later this year.'"

New trial • Preclinical • CNS Disorders • Epilepsy

Ovid Therapeutics Reports First Quarter 2022 Financial Results and Corporate Highlights (Yahoo Finance) - "Ovid anticipates filing an investigational new drug application (IND) for OV329, a potent GABA aminotransferase inhibitor, and initiating Phase 1 trials in the fourth quarter of 2022...Data supporting the preclinical efficacy and safety profile of OV329 are expected to be presented at epilepsy research meetings in the second quarter of 2022."

IND • New P1 trial • Preclinical • 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

Ovid Therapeutics Reports Business Update, Fourth Quarter and Full Year 2021 Financial Results (GlobeNewswire) - "'We are on track to initiate a clinical trial this year for OV329, a novel GABA aminotransferase inhibitor for tuberous sclerosis seizures...Preclinical development of OV350, a direct KCC2 activator, is advancing. Building on experience with Takeda, Ovid expanded its epilepsy franchise by in-licensing a program from AstraZeneca that targets the KCC2 receptor, including lead candidate OV350...Research and development expenses were $18.1 million and $46.9 million for the fourth quarter and for the year ended December 31, 2021...The annual reduction in expenditures was largely due to cessation of clinical development programs related to gaboxadol and soticlestat offset by the license acquisition cost for OV350."

Commercial • New trial • Preclinical • CNS Disorders • Epilepsy

OV329, a novel highly potent γ-aminobutyric acid aminotransferase inactivator, induces pronounced anticonvulsant effects in the pentylenetetrazole seizure threshold test and in amygdala-kindled rats. (PubMed, Epilepsia) - "These results reveal an anticonvulsant profile of OV329 that appears to be superior in both potency and efficacy to vigabatrin and highlight OV329 as a highly promising candidate for the treatment of seizures and pharmacoresistant epilepsies."

Journal • Preclinical • CNS Disorders • Immunology • Pediatrics • Psychiatry