NLS Pharmaceutics announces preclinical data on DOXA platform

NLS Pharmaceutics (NLSP) shared preclinical data demonstrating the potential of its dual orexin receptor agonist platform. AEX-41 and AEX-2, two first-in-class non-sulfonamide DOXAs, are designed to target both orexin-1 and orexin-2 receptors while concurrently inhibiting cathepsins. Cathepsins play significant roles in a variety of physiological processes and may offer a novel therapeutic approach for narcolepsy and other neurological disorders. Key Preclinical Results: The ongoing preclinical study, initiated in October 2024 at the Centre for Neuroscience Research of Lyon, one of Europe’s premier neuroscience research centers, has produced compelling data: Improved Wakefulness and Sleep Architecture: In orexin knockout mice, AEX-41 demonstrated a significant increase in wakefulness and a reduction in REM sleep duration. These effects are crucial for managing the core symptoms of narcolepsy. Comparable Efficacy to Selective OX2R Agonists: The efficacy of AEX-41 was comparable to sulfonamide-derivative selective OX2R agonists under similar experimental conditions, highlighting its potential as a versatile alternative for broader therapeutic application. Multi-Pathway Potential: By targeting both orexin receptors and Cathepsin H inhibition activity, AEX-41 offers a dual-action mechanism that could address not only sleep-wake regulation but also underlying neurodegenerative processes. Starting in 2025, NLS plans to expand its research to investigate the impact on CTSH in animal models of neuroinflammation, a key factor in the progression of neurodegenerative diseases. An Investigational New Drug application is planned for 2026-2027 to support this new avenue of study.