Ovid Therapeutics Presents Pre-Clinical Study Results Demonstrating OV329 Does Not Accumulate in Animal Eyes in Contrast with Vigabatrin
Ovid Therapeutics (NASDAQ: OVID) presented results of a pre-clinical study comparing OV329 to vigabatrin (VGB) at the Epilepsy Pipeline Conference. The study found that OV329 did not accumulate in mouse retinas, eyes, or brains after 48 hours of continuous exposure, unlike VGB which showed ocular accumulation. OV329's unique properties, including potency, short half-life, and rapid tissue elimination, suggest a potentially differentiated ocular safety profile.
The study tested OV329 at 5 mg/kg/day versus VGB at 80 mg/kg/day. OV329 concentrations were undetectable in target tissues, while VGB accumulated preferentially in the retina and other tissues. Ovid is currently conducting a Phase 1 trial of OV329 in healthy volunteers, expected to complete in late 2024, evaluating safety and biomarkers for target engagement and clinical effect.
Ovid Therapeutics (NASDAQ: OVID) ha presentato i risultati di uno studio preclinico che confronta OV329 con vigabatrin (VGB) durante la Epilepsy Pipeline Conference. Lo studio ha rilevato che OV329 non si accumulava nelle retine, negli occhi o nei cervelli dei topi dopo 48 ore di esposizione continua, a differenza del VGB che ha mostrato accumulo oculare. Le proprietà uniche di OV329, comprese potenza, breve emivita e rapida eliminazione tissutale, suggeriscono un potenziale profilo di sicurezza oculare differenziato.
Lo studio ha testato OV329 a 5 mg/kg/giorno contro VGB a 80 mg/kg/giorno. Le concentrazioni di OV329 erano non rilevabili nei tessuti bersaglio, mentre il VGB si accumulava preferenzialmente nella retina e in altri tessuti. Ovid sta attualmente conducendo un trial di Fase 1 di OV329 in volontari sani, previsto per completarsi entro la fine del 2024, valutando la sicurezza e i biomarcatori per il coinvolgimento del bersaglio e l'effetto clinico.
Ovid Therapeutics (NASDAQ: OVID) presentó los resultados de un estudio preclínico que compara OV329 con vigabatrina (VGB) en la Conferencia de Pipeline de Epilepsia. El estudio encontró que OV329 no se acumuló en las retinas, ojos ni cerebros de los ratones después de 48 horas de exposición continua, a diferencia de VGB, que mostró acumulación ocular. Las propiedades únicas de OV329, que incluyen potencia, corta vida media y rápida eliminación tisular, sugieren un posible perfil de seguridad ocular diferenciado.
El estudio probó OV329 a 5 mg/kg/día frente a VGB a 80 mg/kg/día. Las concentraciones de OV329 fueron indetectables en los tejidos objetivo, mientras que VGB se acumuló preferentemente en la retina y otros tejidos. Ovid está llevando a cabo actualmente un ensayo de Fase 1 de OV329 en voluntarios sanos, que se espera finalice a finales de 2024, evaluando la seguridad y biomarcadores para la participación del objetivo y el efecto clínico.
Ovid Therapeutics (NASDAQ: OVID)는 Epilepsy Pipeline Conference에서 OV329와 비가바트린 (VGB)을 비교하는 전임상 연구 결과를 발표했습니다. 연구 결과, OV329은 48시간 연속 노출 후 마우스의 망막, 눈, 뇌에 축적되지 않았으며, 반면 VGB는 안구 축적을 보였습니다. OV329의 고유한 특성, 즉 효력, 짧은 반감기 및 빠른 조직 배출을 통해 잠재적으로 차별화된 안구 안전성 프로파일을 나타낼 수 있습니다.
연구는 OV329을 5 mg/kg/일로, VGB는 80 mg/kg/일로 테스트했습니다. OV329의 농도는 목표 조직에서 검출되지 않았고, VGB는 망막 및 다른 조직에 선호적으로 축적되었습니다. Ovid는 현재 건강한 자원봉사자를 대상으로 한 OV329의 1상 시험을 진행 중이며, 2024년 말까지 완료될 것으로 예상하며, 안전성 및 표적 참여 및 임상 효과를 위한 바이오마커를 평가하고 있습니다.
Ovid Therapeutics (NASDAQ: OVID) a présenté les résultats d'une étude préclinique comparant OV329 à vigabatrine (VGB) lors de la Conférence Pipeline sur l'Épilepsie. L'étude a révélé que OV329 ne s'accumulait pas dans les rétines, les yeux ou les cerveaux des souris après 48 heures d'exposition continue, contrairement à VGB, qui a montré une accumulation oculaire. Les propriétés uniques d'OV329, y compris la puissance, une courte demi-vie et une élimination rapide des tissus, suggèrent un profil de sécurité oculaire potentiellement différencié.
L'étude a testé OV329 à 5 mg/kg/jour contre VGB à 80 mg/kg/jour. Les concentrations d'OV329 étaient indétectables dans les tissus cibles, tandis que VGB s'accumulait préférentiellement dans la rétine et d'autres tissus. Ovid mène actuellement un essai de phase 1 d'OV329 chez des volontaires en bonne santé, dont l'achèvement est prévu pour fin 2024, évaluant la sécurité et les biomarqueurs pour l'engagement ciblé et l'effet clinique.
Ovid Therapeutics (NASDAQ: OVID) stellte auf der Epilepsy Pipeline Conference die Ergebnisse einer vorklinischen Studie vor, die OV329 mit Vigabatrin (VGB) vergleicht. Die Studie ergab, dass OV329 sich nach 48 Stunden kontinuierlicher Exposition nicht in den Retinas, Augen oder Gehirnen von Mäusen anreicherte, im Gegensatz zu VGB, das eine okulare Anreicherung zeigte. Die einzigartigen Eigenschaften von OV329, einschließlich Wirkstärke, kurzer Halbwertszeit und schneller Gewebeeliminierung, deuten auf ein potenziell differenziertes okuläres Sicherheitsprofil hin.
Die Studie testete OV329 mit 5 mg/kg/Tag im Vergleich zu VGB mit 80 mg/kg/Tag. OV329-Konzentrationen waren in den Zielgeweben nicht nachweisbar, während VGB sich bevorzugt in der Retina und anderen Geweben anreicherte. Ovid führt derzeit eine Phase-1-Studie zu OV329 bei gesunden Freiwilligen durch, deren Abschluss für Ende 2024 geplant ist. Dabei werden Sicherheit und Biomarker für die Zielbindung und klinische Wirkung bewertet.
- OV329 showed no accumulation in mouse retinas, eyes, or brains, unlike vigabatrin
- OV329's properties suggest a potentially improved ocular safety profile compared to vigabatrin
- Phase 1 trial of OV329 in healthy volunteers is on track for completion in late 2024
- None.
Insights
The preclinical study results for OV329 are promising and potentially significant for Ovid Therapeutics. Key findings include:
- OV329 did not accumulate in mouse retinas, eyes and brains after 48 hours of exposure, unlike vigabatrin (VGB)
- OV329 showed no signs of ocular accumulation at therapeutic doses (5 mg/kg)
- Previous studies showed no retinal tissue pathology with OV329 at 45 days, while VGB did show retinal cell degradation
These results suggest OV329 may have a better safety profile than VGB, particularly regarding ocular toxicity. The drug's short half-life (1.5 hours) and rapid tissue elimination could be key advantages. However, it's important to note that these are preclinical results and human trials are needed to confirm these findings.
The ongoing Phase 1 trial, set to complete in late 2024, will be critical in assessing OV329's safety and potential efficacy in humans. The use of biomarkers for target engagement and clinical effect is a smart approach to gather early evidence of the drug's mechanism of action.
While these results are encouraging, investors should remain cautious as many promising preclinical candidates fail in human trials. The
From a financial perspective, these preclinical results for OV329 are potentially significant for Ovid Therapeutics:
- If OV329 proves to have a better safety profile than vigabatrin in human trials, it could capture a significant portion of the epilepsy treatment market
- The global epilepsy drugs market was valued at
$16.56 billion in 2020 and is expected to reach$20.33 billion by 2027 - Ovid's current market cap of
$79 million suggests significant upside potential if OV329 succeeds in clinical trials
However, investors should consider several factors:
- Drug development is risky, with many candidates failing in later-stage trials
- The company will likely need additional funding to complete clinical trials, which could lead to dilution
- Commercialization, if successful, is still years away
The upcoming Phase 1 results in late 2024 will be a important catalyst. Positive results could drive significant stock appreciation, while negative results could severely impact the company's valuation. Given the early stage and speculative nature of this investment, it's suitable only for investors with high risk tolerance and a long-term horizon.
- Study found OV329 cleared and remained undetectable in the retina, eye, and brain tissues of mice, unlike vigabatrin which has repeatedly shown to preferentially accumulate in mouse retinas, eyes, and other tissues
- OV329’s potency, mechanism of inhibition, short half-life, rapid tissue elimination and prolonged pharmacodynamic effect suggests it delivers a differentiated ocular safety and efficacy profile from vigabatrin
- A Phase 1 trial evaluating OV329 in healthy volunteers is on-track for completion in late 2024 and will evaluate safety and two biomarkers for target engagement and evidence of clinical effect
NEW YORK, Sept. 26, 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 presented the results of a head-to-head animal study evaluating whether OV329 could be found to accumulate in mouse retinas and brains, as has been previously shown to occur with vigabatrin (VGB) the only FDA-approved GABA-aminotransferase (GABA-AT) inhibitor.
The findings, which were presented via a poster at the Epilepsy Pipeline Conference, found that OV329 cleared and remained undetectable in the retinas, eyes, and brains of mice after 48 hours of continuous exposure via a sub-cutaneous osmotic pump, suggesting a lack of accumulation. In contrast, ocular accumulation of VGB was confirmed within this period. Full results from the head-to-head animal study will be presented at the 2024 American Epilepsy Society conference in December.
These results replicate previously published findings that indicate VGB preferentially and rapidly accumulates within mouse tissue and plasma, including retina, visual cortex, and brain at subtherapeutic doses (70 mg/kg).1,2 In contrast, a therapeutic dose of OV329 in animals (5 mg/kg) did not show signs of ocular accumulation in the same study design. These results complement previously presented studies which showed that therapeutic doses of OV329 (3 mg/kg) did not result in retinal tissue pathology at 45 days in Sprague Dawley rats, an animal model that investigates structural and functional ocular toxicity.3 In contrast, VGB did show retinal cell degradation at the therapeutic dose in animals of 300 mg/kg at 45 days.
“Today’s findings suggest a compelling and potentially differentiated profile for OV329. A combination of attributes potentially enables OV329 to deliver an anti-convulsant effect at lower, safer, and non-sedative doses without the same ocular changes seen with vigabatrin,” stated Zhong Zhong, Ph.D. and Chief Scientific Officer of Ovid Therapeutics. “Specifically, OV329’s potency, tissue-clearance, mechanism of inhibition, pharmacokinetic and pharmacodynamic profile suggest it is highly efficient at binding to, and inhibiting the GABA-AT enzyme, and then, rapidly clearing the tissue. We believe this unique combination of drug characteristics may have application in a variety of conditions characterized by hyperexcitation,” he added.
STUDY METHODS AND RESULTS
At the Epilepsy Pipeline Conference, Ovid presented results from a preclinical head-to-head study intended to evaluate the tissue distribution of OV329 and VGB following continuous infusion via a subcutaneous osmotic pump in mice for two days. This study replicates and builds upon published research examining how VGB preferentially accumulates in the retina, eye, and visual cortex.1,2 The presented study tested OV329 at 5 mg/kg/day, compared to 80 mg/kg/day of VGB. Notably, the dose studied for OV329 led to exposures above those expected to be reached in humans, while VGB was tested at the established therapeutic exposure level in humans.
- OV329 was not observed to accumulate in the retina, eye, or brain. The concentrations of OV329 in target tissues were below the lower limit of quantification, or undetectable, indicating that OV329 clears and does not accumulate in the retina, eye, or brain. It is thought that OV329’s short-half-life of 1.5 hours, quick tissue elimination properties, and prolonged pharmacodynamic effect may reduce the risk of ocular accumulation to occur.
- VGB has been shown to accumulate in the eye at sub-therapeutic doses in animals and was associated with ocular toxicity at therapeutic doses in humans. Previous animal studies have demonstrated VGB’s tendency to accumulate preferentially in the retina, eye, visual cortex and brain with significantly higher retina/plasma ratios observed (6.1 ± 0.29).1 VGB also demonstrated a higher preference of the biological active S- (+) enantiomer to accumulate in tissues suggesting the potential for more prominent off target effects.4
OV329 PHASE 1 TRIAL
Ovid anticipates the completion of a Phase 1 single ascending dose (SAD) and multiple ascending dose (MAD) study of OV329 in healthy volunteers in late 2024. This safety and tolerability study is additionally applying magnetic resonance spectrometry and transcranial magnetic stimulation, respectively, as biomarkers of target engagement and potential clinical effect.
The poster presented at the Epilepsy Pipeline Conference can be found under the Posters and Publications section of Ovid’s website at investors.ovidrx.com
ABOUT OV329
OV329 is a next-generation anti-seizure medicine being developed for the potential treatment of rare and treatment-resistant forms of epilepsy and seizures, such as seizures associated with tuberous sclerosis complex, infantile spasms and conditions with focal onset seizures. OV329 inhibits GABA-AT, which is an enzyme in the brain that catabolizes GABA and thereby increases endogenous levels of GABA, the brain’s inhibitory neurotransmitter. By increasing GABA, OV329 is thought to reduce neuronal hyperexcitability and suppress seizures.
OV329 was rationally designed to improve upon and potentially supplant VGB, the only FDA-approved GABA-AT inhibitor. VGB is an approved anti-convulsant for the treatment of infantile spasms and refractory complex partial seizures. Use of VGB has been limited by its Black Box warning for permanent bilateral peripheral visual field constriction, a form of irreversible blindness that occurs in some patients taking the drug. Prior studies have shown OV329 to be 200-to-1,000-fold more potent than VGB. OV329 has been shown to possess favorable tissue clearance characteristics, while delivering prolonged PD effect through both phasic (synaptic) and tonic (extrasynaptically) inhibition, thereby strengthening inhibitory neurotransmission in the neuronal milieu.
About Ovid Therapeutics
Ovid Therapeutics Inc. is a New York-based biopharmaceutical company that is dedicated to improving the lives of people affected by rare epilepsies and brain conditions with seizure symptoms. Ovid 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 (ROCK2) inhibitor, 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 potassium-chloride co-transporter 2 (KCC2), 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 potentially differentiated ocular safety and efficacy profile of OV329; the expected timing of completion of Ovid’s Phase 1 SAD and MAD trial evaluating OV329 in healthy volunteers; the therapeutic potential of OV329, including potential anti-convulsant effect, tolerability and non-sedative dosing; the potential application of OV329 to a variety of conditions characterized by hyperexcitation; OV329’s potential as a treatment of rare and treatment-resistant epilepsy and seizures; the potential therapeutic opportunity of OV888/GV101 capsule, OV329 and OV350; and other statements that are not historical fact. You can identify forward-looking statements because they contain words such as “anticipates,” “believes,” “expects,” “intends,” “may,” “plan,” “potentially,” and “will,” 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, the risk that results of preclinical studies or earlier clinical trials are not necessarily predictive of future results, our drug candidates may not have favorable results in planned or future preclinical studies or clinical trials, or may not receive regulatory approval. 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 August 13, 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.
Investor Relations:
Garret Bonney
617-735-6093
gbonney@ovidrx.com
Media:
Raquel Cabo
rcabo@ovidrx.com
________________________
1 Walters DC, et al. Preclinical tissue distribution and metabolic correlations of vigabatrin, an antiepileptic drug associated with potential use-limiting visual field defects. Pharmacol Res Perspect. 2019 Jan 7
2 Colmers PLW, et al. Sustained Inhibition of GABA-AT by OV329 Enhances Neuronal Inhibition and Prevents Development of Benzodiazepine Refractory Seizures. eNeuro. 2024 Jul
3 Bailer, et al. Progress report on new antiepileptic drugs: A summary of the Sixteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XVI): I. Drugs in preclinical and early clinical development. Epilepsia. 2022 Aug.
4 Walters DC, et al. Preferential accumulation of the active S-(+) isomer in murine retina highlights novel mechanisms of vigabatrin-associated retinal toxicity. Epilepsy Res. 2021 Feb.
FAQ
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