eNeuro Publishes Findings on the Anti-Convulsant Properties of OV329 and Its Potential Effectiveness in Treatment-Resistant Seizures

Rhea-AI Summary

Ovid Therapeutics announced the publication of preclinical studies in eNeuro, showcasing OV329's potential effectiveness in treating drug-resistant seizures. OV329, a next-gen GABA-AT inhibitor, demonstrated higher potency compared to vigabatrin, an FDA-approved GABA-AT inhibitor. Sustained exposure to OV329 in mice reduced GABA-AT activity and increased GABA levels in the brain, potentially offering robust and sustained seizure reduction. Additionally, OV329 reduced status epilepticus severity and prevented benzodiazepine resistance development in mice. These findings suggest OV329's differentiated profile and potential for better safety, dosing, and efficacy in refractory seizure treatment.

Positive

• OV329 demonstrated higher potency (IC50 of 104.1 nM) for the GABA-AT target than vigabatrin (183.8 µM).
• OV329 reduced GABA-AT activity and increased GABA levels in mouse brains, indicating potential for sustained anti-seizure properties.
• Preclinical studies showed OV329 could reduce the severity of status epilepticus and prevent benzodiazepine resistance in mice.
• OV329's design aims for better selectivity and improved safety compared to established GABA-AT inhibitors, with a marked increase (200 - 1000 fold) in potency over vigabatrin.

Negative

• None.

Insights

Medical Research Analyst

The recent publication of OV329's preclinical study results in eNeuro presents some promising data for Ovid Therapeutics. The study shows that OV329 has a higher potency compared to vigabatrin, an already FDA-approved drug, which suggests it could be more effective at lower doses. This increased potency could potentially result in fewer side effects, a significant advantage, especially for patients with drug-resistant seizures. Moreover, the data suggests OV329 can reduce the severity of status epilepticus (SE) and prevent the development of benzodiazepine resistance in preclinical models.

For retail investors, this is an encouraging sign. If OV329's efficacy and safety profile hold up in human trials, it could lead to a breakthrough in treatments for drug-resistant epilepsy, a large and underserved market. However, it's important to remain cautious as the study is still in preclinical stage; these results need to be confirmed in clinical trials involving humans, which are more complex and can often yield different outcomes.

Financial Analyst

From a financial standpoint, the publication of OV329's preclinical results is a positive development for Ovid Therapeutics. An effective treatment for drug-resistant seizures would potentially open up new revenue streams and strengthen their position in the biopharmaceutical market. The current data notably differentiates OV329 from existing treatments like vigabatrin with its higher potency and potentially better safety profile. These factors could translate into a competitive advantage if the drug progresses successfully through clinical trials.

For investors, the key takeaway is the potential for significant future returns. However, the stock's performance will likely remain volatile, reflecting the uncertainties associated with drug development. Investors should closely monitor upcoming clinical trial results and regulatory updates to assess Ovid's progress and any potential delay risks or unforeseen challenges.

• Sustained exposure to OV329 in preclinical models reduced GABA-aminotransferase (GABA-AT) activity, increased steady state GABA levels in the brain, and induced phasic and tonic inhibition
  
• OV329 demonstrated anti-convulsant effects in mice, reducing the severity of status epilepticus and preventing the development of benzodiazepine-resistant seizures
  
• OV329 was shown to have a higher potency (as measured by IC₅₀) for the GABA-AT target than published studies of vigabatrin, an FDA-approved GABA-AT inhibitor
  

NEW YORK, July 10, 2024 (GLOBE NEWSWIRE) -- Ovid Therapeutics Inc. (NASDAQ: OVID), a biopharmaceutical company dedicated to improving the lives of people affected by rare epilepsies and brain conditions, 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.

OV329 is a rationally designed, next-generation GABA-AT inhibitor in development by Ovid for the potential treatment of drug-resistant seizures. OV329 is intended to have higher potency and preferable safety and dosing relative to the available medicine in this class. To support OV329’s clinical development, the preclinical studies published in eNeuro were conducted jointly by the Department of Neuroscience at Tufts University School of Medicine, the Department of Neuroscience, Physiology and Pharmacology at the University College London and Ovid.

“These preclinical studies provide further support that OV329 has a differentiated profile from prior anti-convulsant therapies and may have the potential to deliver robust and sustained seizure reduction,” said Zhong Zhong, Ph.D., Chief Scientific Officer of Ovid Therapeutics. “OV329 was designed for better selectivity and improved safety relative to established GABA-AT inhibitors. These encouraging results provide us with further confidence of what we may hope to see in patients with refractory seizures.”

PUBLICATION HIGHLIGHTS

• Sustained exposure to low doses of OV329 delivered reduced GABA-AT activity and increased GABA accumulation in mouse brains. 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.
  
• Repeat, low doses of OV329 delivered synaptic and extra synaptic inhibition in mice suggesting it may provide sustained anti-convulsant activity. Mice consistently treated with a low dose of 0.5 mg/kg of OV329 over six days were shown to experience phasic (synaptic) and tonic (extra synaptic) inhibition as compared to placebo. These findings, which were measured by electrophysiological recordings, may differentiate OV329 from other anti-convulsant medicines and suggest the potential to provide broad inhibitory neurotransmission.
  
• Sustained doses of OV329 reduced the severity of status epilepticus (SE) and prevented development of benzodiazepine resistance in a mouse model with similarities to SE patients. In a kainic acid-induced SE mouse model, which has similarities to patients in a state of SE, electroencephalogram (EEG) recordings demonstrated that OV329 significantly reduced the EEG power of SE when compared with placebo (vehicle: 2.0 ± 0.3 times 10^-6 V² compared to OV329: 0.9 ± 0.2 times 10^-6 V²; two-tailed Welch’s t test; p=0.005; N=6 mice). Additional findings using this benzodiazepine resistant model showed that mice pre-treated with OV329 were able to restore the anti-convulsant effects of diazepam.
  
• OV329 was shown to have superior potency (as measured by IC₅₀) to the GABA-AT target than published results for vigabatrin (VGB). OV239 had an IC₅₀ of 104.1 nM for GABA-AT, while the published IC₅₀ for VGB was 183.8 µM.
  

Collectively, the studies published in eNeuro reinforce prior findings, which suggest OV329 is a potent, highly selective GABA-AT inhibitor. OV329 appears to increase GABA levels in animal brains through both phasic and tonic inhibition, which indicates that it may have the potential to deliver sustained anti-seizure properties at very low doses in humans. Additionally, cumulative and single doses of OV329 have been shown to reduce the severity of SE and restore the effectiveness of diazepam in an acute benzodiazepine-resistant seizure mouse model.

The authors note that the safety profile of OV329 is believed to differentiate it from VGB, a previously approved GABA-AT inhibitor. VGB, has a known toxicity and is associated with visual field loss. The underlying mechanisms of VGB’s toxicity may result from the high daily dose, poor blood brain barrier permeability, low activation efficiency and possible off-target effects. OV329 was rationally designed to be more potent and specific with the desire to avert these safety challenges. Specifically, OV329 exhibits a marked increase (200 - 1000 fold) in potency for GABA-AT compared to VGB, it demonstrates the potential for faster tissue clearance than VGB but with a prolonged pharmacodynamic effect, and it does not irreversibly inhibit GABA-AT activity.

Full-text of the OV329 publication in eNeuro is available here. 

About OV329
OV329 is a potential next-generation GABA-AT inhibitor being developed for the potential treatment of rare and treatment-resistant forms of epilepsy and seizures, such as seizures associated with status epilepticus, tuberous sclerosis complex, infantile spasms and conditions with focal onset seizures. Low levels of GABA, the primary inhibitory neurotransmitter in the brain, have been linked to neuronal hyperexcitability. OV329 is believed to work by reducing the activity of GABA-AT, thereby increasing levels of GABA in the brain, and potentially suppressing neuronal hyperexcitability known to cause seizures. OV329 may be a potential best-in-class GABA-AT inhibitor.

About Ovid Therapeutics
Ovid Therapeutics Inc. is a New York-based biopharmaceutical company that is dedicated to meaningfully improving the lives of people affected by certain epilepsies and brain conditions with seizure symptoms. The Company is advancing a pipeline of novel, targeted small molecule candidates that modulate the intrinsic and extrinsic factors involved in neuronal hyperexcitability causative of seizures and other neurological symptoms. Ovid is developing: OV888/GV101 capsule, a potent and highly selective Rho-associated coiled-coil containing protein kinase 2 inhibitor capsule, for the potential treatment of cerebral cavernous malformations and other rare central nervous system diseases; OV329, a GABA-AT inhibitor, a potential therapy for treatment-resistant seizures; and OV350, a direct activator of the KCC2 transporter, for the potential treatment of epilepsies and other psychiatric conditions. For more information about these and other Ovid research programs, please visit www.ovidrx.com.

Forward-Looking Statements
This press release includes certain disclosures by Ovid that contain “forward-looking statements,” including, without limitation: statements regarding the potential use and development of OV329, OV888/GV101 capsule, and OV350; OV329’s potential best-in-class status and the ability to become a treatment for rare and treatment-resistant forms of epilepsy and seizures, including the potential to deliver robust and sustained seizure reduction at very low doses in humans; the potential potency, efficacy, safety and or tolerability of OV329; and the potential timing of initiation of Phase 2 clinical trials in OV329. You can identify forward-looking statements because they contain words such as “could,” “demonstrates,” “future,” “expects,” “hopes,” “intends,” “may,” “plans,” “potential,” “progress,” and “shows” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances). Forward-looking statements are based on Ovid’s current expectations and assumptions. Because forward-looking statements relate to the future, they are subject to inherent uncertainties, risks and changes in circumstances that may differ materially from those contemplated by the forward-looking statements, which are neither statements of historical fact nor guarantees or assurances of future performance. Important factors that could cause actual results to differ materially from those in the forward-looking statements include, without limitation, uncertainties inherent in the preclinical and clinical development and regulatory approval processes, risks related to Ovid’s ability to achieve its financial objectives, the risk that Ovid may not be able to realize the intended benefits of its technology or its business strategy, or risks related to Ovid’s ability to identify business development targets or strategic partners, to enter into strategic transactions on favorable terms, or to consummate and realize the benefits of any business development transactions. Additional risks that could cause actual results to differ materially from those in the forward-looking statements are set forth under the caption “Risk Factors” in Ovid’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (“SEC”) on May 14, 2024, and in future filings Ovid makes with the SEC. Any forward-looking statements contained in this press release speak only as of the date hereof, and Ovid assumes no obligation to update any forward-looking statements contained herein, whether because of any new information, future events, changed circumstances or otherwise, except as otherwise required by law.

Contacts

Investor Relations
Garret Bonney
617-735-6093
IR@ovidrx.com

Media
Raquel Cabo
646-647-6553
RCabo@ovidrx.com

FAQ

What are the findings of the preclinical studies on OV329 published in eNeuro?

The studies found that OV329 reduced GABA-AT activity, increased GABA levels in mouse brains, reduced status epilepticus severity, and prevented benzodiazepine resistance. OV329 also showed higher potency than vigabatrin.

How does OV329 compare to vigabatrin in terms of potency?

OV329 demonstrated a significantly higher potency (IC50 of 104.1 nM) for the GABA-AT target compared to vigabatrin, which has an IC50 of 183.8 µM.

What potential benefits does OV329 offer for drug-resistant seizure treatment?

OV329 may provide robust and sustained seizure reduction, reduce the severity of status epilepticus, prevent benzodiazepine resistance, and offer better safety and dosing compared to existing GABA-AT inhibitors.

What impact did OV329 have on GABA levels in the brain during the studies?

OV329 increased GABA levels in the brains of treated mice, indicating broad inhibitory neurotransmission and potential sustained anti-seizure properties.

What was the effect of OV329 on status epilepticus in preclinical models?

OV329 significantly reduced the severity of status epilepticus and prevented the development of benzodiazepine resistance in a mouse model.