Avenue Therapeutics Announces Publication in Drug Development Research Highlighting First-In-Class Preclinical Data of BAER-101 in a Translational Model of Absence Epilepsy
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Insights
The recent preclinical data on BAER-101 suggests a significant advancement in epilepsy treatment. The ability of BAER-101 to fully suppress seizures in the GAERS model is a noteworthy finding, given the model's high predictive value for human response. The selective targeting of GABAA α2 and α3 subtypes by BAER-101, while avoiding α1 and α5, is crucial. This selectivity could lead to fewer side effects like dizziness, somnolence and cognitive impairment, which are common with other GABAA positive allosteric modulators (PAMs). Furthermore, the absence of adverse safety events even at doses 300 times the minimal effective dose (MED) is promising for the drug's safety profile.
Understanding the pharmacology, BAER-101's lack of activity at the α1- and α5-subtypes of GABAAR is significant. Engagement of the α5-subtype has been associated with potential anti-cognitive effects, which BAER-101 seems to avoid. This could position BAER-101 as a frontrunner in the epilepsy treatment landscape, especially for patients who are sensitive to cognitive side effects.
BAER-101's pharmacodynamics indicate a paradigm shift in seizure management. The drug's mechanism, which selectively targets synaptic GABAA receptors without affecting the α1 and α5 subtypes, could offer a new avenue for patients with drug-resistant epilepsy or those who have experienced tolerance and abuse with existing treatments. The minimal effective dose of 0.3 mg/kg indicates a high potency, which may translate into lower required dosages in humans, potentially reducing the risk of side effects and improving patient compliance.
From a pharmacological standpoint, the fast onset and stability of BAER-101's effect are advantageous for seizure control. Additionally, the dose-dependent reduction of spike-wave discharges without safety concerns up to 300x the MED provides a substantial therapeutic window. This could benefit the dosing strategy in clinical settings, allowing for flexible and patient-specific treatment plans.
The announcement regarding BAER-101's preclinical success is likely to have positive implications for Avenue Therapeutics' market performance. Investors typically respond well to robust preclinical results, especially when a compound demonstrates potential to fill an unmet medical need. The epilepsy market, with an estimated patient population of 65 million worldwide, represents a significant commercial opportunity for Avenue. The company's strategic plan to initiate a Phase 2a trial, pending necessary financing, could attract potential partnerships or funding opportunities.
However, it is important to note that the journey from preclinical to commercial success is fraught with challenges, including regulatory hurdles and the need for substantial capital. The dependency on strategic partnerships for financing the Phase 2a clinical trial adds a layer of risk for investors. Avenue's current financial health, market conditions and investor sentiment will all play roles in the company's ability to secure the required funding and advance BAER-101's development.
-In vivo data supports BAER-101’s unique ability to significantly suppress seizures using the SynapCell's Genetic Absence Epilepsy Rat from Strasbourg (“GAERS”) model of absence epilepsy-
MIAMI, Feb. 22, 2024 (GLOBE NEWSWIRE) -- Avenue Therapeutics, Inc. (Nasdaq: ATXI) (“Avenue” or the “Company”), a specialty pharmaceutical company focused on the development and commercialization of therapies for the treatment of neurologic diseases, today announced the publication of preclinical in vivo data in Drug Development Research highlighting BAER-101’s full suppression of seizure activity using the Genetic Absence Epilepsy Rats from Strasbourg (“GAERS”) model of absence epilepsy. Data published showcase BAER-101’s ability to selectively target GABAA α2 and α3 subtypes more than α1 and α5, potentially improving anti-convulsant and anxiolytic activity while minimizing the risk of tolerance and abuse associated with existing treatments in this drug class.
The publication describes the extent of anti-seizure activity of BAER-101 in the GAERS model, a widely used and translationally relevant animal model. The study demonstrated full suppression of seizure activity with a minimal effective dose (MED) of 0.3 mg/kg. The effect of BAER-101 was fast in onset and stable throughout the duration of testing. Results from the testing showed that the number of spike-wave discharges were dose-dependently reduced by BAER-101, and no adverse safety events were observed up to a dose 300x the MED.
BAER-101 is the first clinical candidate which is selective for only α2,3 and not for α1 or α5, a pharmacology consistent with anti-seizure activity that avoids the adverse side effects common to the GABAA positive allosteric modulators (PAM) class. Specifically, the α1-subtype of GABAAR is associated with dizziness and somnolence in both animal and human studies, and the α5-subtype of GABAAR is thought to play a key role in synaptic plasticity, cognition, and memory, suggesting that engagement of α5 risks anti-cognitive effects. The pharmacology of BAER-101 lacks activity at both the α1- and α5-subtypes of GABAAR, and these findings indicate that BAER-101’s on-target engagement with a selective subset of synaptic GABAARs is sufficient to suppress absence seizures while avoiding adverse side effects common to the GABAA PAM class.
“Epilepsy remains one of the most prevalent neurological diseases worldwide, with a population of approximately 65 million patients, but there remains a great unmet need for a safe and effective treatment option that suppresses seizure activity without drug resistance or harmful side effects such as sedation, cognitive impairment, ataxia and addiction,” said Alexandra MacLean, M.D., Chief Executive Officer of Avenue. “The preclinical data published in Drug Development Research demonstrate BAER-101’s ability to fully suppress seizures in the GAERS model, a translational animal model for anti-seizure drug development with a documented high predictability of response in humans. Additionally, BAER-101 demonstrated full efficacy with a minimal effective dose of 0.3 mg/kg, indicating that BAER-101 is the most potent compound yet reported in this model, as well as the first to show that a GABA PAM that is selective for the α2 and α3-subtype GABAARs is active in this model. Building on BAER-101’s proven safety profile in over 700 patients and healthy human volunteers, these first-in-class preclinical findings support BAER-101’s continued development in a Phase 2a trial.”
Subject to obtaining the necessary financing, which could be provided through a strategic partnership, Avenue plans to initiate a Phase 2a clinical trial of BAER-101 to further study its anti-seizure properties in patients with common or rare epilepsies.
About Avenue Therapeutics
Avenue Therapeutics, Inc. (Nasdaq: ATXI) is a specialty pharmaceutical company focused on the development and commercialization of therapies for the treatment of neurologic diseases. It is currently developing three assets including AJ201, a first-in-class asset for spinal and bulbar muscular atrophy, BAER-101, an oral small molecule selective GABAA α2, α3 receptor positive allosteric modulator for CNS diseases, and IV tramadol, which is in Phase 3 clinical development for the management of acute postoperative pain in adults in a medically supervised healthcare setting. Avenue is headquartered in Miami, FL and was founded by Fortress Biotech, Inc. (Nasdaq: FBIO). For more information, visit www.avenuetx.com.
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Contact:
Jaclyn Jaffe
Avenue Therapeutics, Inc.
(781) 652-4500
ir@avenuetx.com
FAQ
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