NLS Pharmaceutics highlights preclinical program for AEX-41, AEX-2

NLS Pharmaceutics (NLSP) provided insights into the preclinical program evaluating 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. This unique approach aims to address the unmet therapeutic needs in narcolepsy and related neurological disorders. The ongoing studies are conducted at the Centre for Neuroscience Research of Lyon, a world-class institution specializing in sleep and neurological research. The experimental framework is designed to explore the therapeutic potential of AEX compounds using an international validated orexin knockout mouse model of narcolepsy. Key elements of the study include: Study Objectives: Promote Wakefulness: Evaluate the impact of AEX compounds on maintaining wakefulness in narcoleptic mice. Enhance Sleep Quality: Assess improvements in sleep architecture and stability. Suppress Cataplexy Attacks: Measure reductions in the frequency and severity of cataplexy, a hallmark symptom of narcolepsy. Methodology: The study leverages cutting-edge EEG/EMG technology to monitor brain activity and muscle tone, providing precise data on wakefulness, non-rapid eye movement, and rapid eye movement sleep phases. Post-surgical recovery is followed by controlled drug administration, ensuring accurate measurement of the compound’s efficacy. Robust Experimental Design: The study aims to evaluate the potential superiority of AEX compounds over existing therapies through a two-part approach: Part 1: Direct evaluation of AEX compounds performance on key metrics such as sustained wakefulness and improved sleep architecture. Part 2: Assessment of compound efficacy under challenging stress conditions, including sleep deprivation, to test the robustness and durability of their effects. While existing selective OX2R agonists have demonstrated efficacy in managing narcolepsy symptoms, DOXA are expected to surpass these benchmarks. By engaging both OX1R and OX2R receptors and addressing broader neurological pathways, AEX-41 and AEX-2 offer the potential for enhanced therapeutic outcomes, including greater wakefulness stability and improved sleep quality under real-world conditions. NLS remains committed to advancing its pipeline and anticipates providing further updates as the preclinical program progresses. First results from the ongoing study are expected to be shared in early December 2024.