NLS Pharmaceutics Ltd. announced the publication of the latest patent application (PCT/WO2024115797) by Aexon Labs with the World Intellectual Property Organization (WIPO). The patent will be used by NLS pursuant to its existing and previously announced license agreement with Aexon Labs. Key Highlights: Innovative Dual Orexin Receptor Agonists: The patent application introduces a completely new series of molecules, licensed to NLS from Aexon Labs, acting primarily as dual orexin receptor agonists (OX1R and OX2R).

These multitarget compounds have demonstrated efficacy in vitro, showing potential to not only mitigate narcolepsy symptoms, but also to slow the progression of neurodegenerative diseases. Non-Sulfonamide Compounds: Unlike many current treatments acting as orexin receptor agonists, these innovative non-sulfonamide derivatives have the potential to reduce the risk of side effects and adverse reactions associated with traditional sulfonamide medications. This characteristic may both broaden their potential use and improve patient safety.

Mechanism of Action: The new molecules enhance neurotransmitter release and protect neuronal health by modulating orexin receptors (OX1R/OX2R) and integrating neuroinflammation protection through cathepsin H (CTSH) inhibition. This combined action targets both sleep regulation and neurodegeneration, offering the potential for significant therapeutic benefits for patients. Therapeutic Implications: CTSH is involved in proteolytic degradation and antigen presentation, influencing autoimmune responses in narcolepsy.

Inhibiting CTSH could protect neuronal cells by disrupting the proteolytic pathway. When combined with dual orexin receptor agonist action, this approach could significantly enhance orexin signaling stability and mitigate symptoms. Neuroprotective strategies focusing on reducing neuroinflammation and modulating immune responses could further improve therapeutic outcomes. Focus on Narcolepsy: These compounds are designed primarily to treat narcolepsy by activating orexin pathways, which are crucial for maintaining wakefulness and regulating sleep patterns.

By addressing the core pathology of narcolepsy, these dual orexin receptor agonists provide a novel and effective treatment approach. Application in Neurodegenerative Diseases:Beyond narcolepsy, these multitarget molecules show promise for treating conditions like Parkinson?s disease by targeting neurodegenerative processes such as OX1R and a-synuclein. This represents a significant advancement in developing treatments that could improve quality of life and disease outcomes for patients.

Recent Advances and Presentations from NLS Pharmaceutics and Aexon Labs: At Sleep 2024 (Houston, June 1-5), data on selective OX2R agonists highlighted their limitations, including receptor desensitization and reduced efficacy at higher doses. In contrast, a new generation of compounds from Aexon Labs, presented at the 2024 ASCP Annual Meeting (Miami, May 27-31), targets both OX1R and OX2R while also preventing the destruction of orexin cells through an inhibitory effect on CTSH. These multitarget compounds, with their broader affinity, show fewer issues related to high-affinity binding and efficacy loss, suggesting a more stable pharmacological profile and better long-term outcomes.