Avenue Therapeutics Announces High Potency & Full Efficacy in a Model of Generalized Seizures for its Novel GABA-A Receptor Potentiator Supporting Phase 2 Clinical Study

Avenue Therapeutics, Inc. recently announced BAER-101, the company’s potentially best-in-class selective GABA-A α2,3 positive allosteric modulator (PAM), significantly suppressed seizures in a translational animal model of absence epilepsy.

“These preclinical results demonstrate the potential of BAER-101 to improve the current treatment landscape of epilepsy with a differentiated approach designed to improve the safety profile compared to existing drugs, which are often not well-tolerated due to side effects including sedation, cognitive impairment, ataxia and addiction,” said Alexandra MacLean, MD, Chief Executive Officer of Avenue. “As we advance toward potentially initiating a Phase 2a study in 2024, we are encouraged by these results, showing BAER-101’s best-in-class potential for patients with increased tolerability, potency and efficacy.”

BAER-101 underwent preclinical in vivo evaluation in SynapCell’s Genetic Absence Epilepsy Rat from Strasbourg (GAERS) model of absence epilepsy. The GAERS model mimics behavioral, electrophysiological and pharmacological features of human absence seizures. The GAERS model is a proven, early, informative indicator of efficacy in anti-seizure drug development, with high predictability of response in humans. In the model, BAER-101 demonstrated full suppression of seizure activity with a minimal effective dose of 0.3 mg/kg, PO. The effect was fast in onset and stable throughout the duration of testing.

BAER-101 has previously been shown to be safe with minimal side effects in clinical studies of hundreds of patients in a program targeting a different indication by AstraZeneca. The combination of safety, tolerability and efficacy in an established translationally relevant epilepsy model support BAER-101’s continued development. The selective potentiation of alpha 2,3-containing GABA-A receptors with minimal impact on α1 and α5-containing GABA-A receptors differentiates BAER-101 from competitors, and predicts a lower potential for sedation, motor incoordination, cognitive impairment and/or tolerance. Further study of the anti-seizure properties of BAER-101 is being planned in patients with focal seizures and other seizure disorders for which current treatments are not fully efficacious.

“As an experienced neurologist treating patients with epilepsy, I believe the potency, tolerability and efficacy of BAER-101 is exciting, as it creates an opportunity to improve the treatment of seizures in a field where many of the approved treatments have limited efficacy and/or are dose-limited by side effects,” said Amy Chappell, MD, FAAN, experienced neuroscience drug developer, former Eli Lilly and Company executive, and consultant to the company.

The detailed study results are expected to be presented at an upcoming scientific meeting.

Avenue is developing BAER-101 via its subsidiary Baergic Bio for epilepsy disorders. BAER-101 is a PAM of α2,3 subunit‐containing GABA-A receptors with minimal activity at α1 or α5‐containing receptors, which are believed to mediate many of the issues impacting the medical use of benzodiazepines such as those noted with diazepam use (tolerance, dependence, abuse, sedation and impaired cognition). As a result, BAER-101 may have the potential to treat epilepsy, anxiety and other disorders in which benzodiazepines are currently used, while minimizing the benzodiazepine associated adverse effects. BAER-101 was licensed in from AstraZeneca with a large safety database in over 700 patients and an efficacy signal in a ​subset of patients with anxiety.

Absence epilepsy is a form of epileptic syndrome where patients show generalized non-convulsive seizures characterized by a brief unresponsiveness to environmental stimuli and cessation of activity. In human, typical absence seizures are associated with bilateral, synchronous and regular spike-and-wave discharges (SWD). SynapCell’s world-exclusive model, the GAERS, displays spontaneous SWD and has become the “state of the art” translational a reference model for the past thirty years. Most of the drugs that have been studied in the GAERS model work in focal as well as generalized seizures in humans.

Avenue Therapeutics, Inc. (Nasdaq: ATXI) is a specialty pharmaceutical company focused on the development and commercialization of therapies for the treatment of neurologic diseases. The company 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 GABA-A α2/3 receptor positive allosteric modulator for CNS diseases, and IV Tramadol, which is in Phase 3 clinical development for the management of moderate-to-moderately-severe 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.