The new patent application from Aexon Labs, licensed to NLS Pharmaceutics, covers dual orexin receptor agonists designed to treat narcolepsy and neurodegenerative diseases.


Summary: NLS Pharmaceutics Ltd announced the publication of a new patent application by Aexon Labs with the World Intellectual Property Organization, introducing a novel series of dual orexin receptor agonists. These compounds are designed to treat narcolepsy and neurodegenerative diseases like Parkinson’s. The non-sulfonamide derivatives aim to reduce side effects and enhance patient safety. This patent falls under an existing license agreement between NLS and Aexon Labs.

Key Takeaways:

  1. Patent Introduction: The patent covers dual orexin receptor agonists targeting narcolepsy and neurodegenerative diseases.
  2. Non-Sulfonamide Compounds: These derivatives aim to reduce side effects compared to traditional treatments.
  3. Therapeutic Potential: The compounds show promise in both mitigating narcolepsy symptoms and slowing neurodegenerative disease progression.

NLS Pharmaceutics Ltd announced the publication of a new patent application by Aexon Labs with the World Intellectual Property Organization, highlighting advancements in dual orexin receptor agonists for treating narcolepsy and neurodegenerative diseases.

The patent for next-gen dual non-sulfonamide orexin receptor agonists will be used by NLS pursuant to its existing and previously announced license agreement with Aexon Labs.

“This new patent application covers groundbreaking advancements in a novel series of dual orexin receptor agonists targeting narcolepsy as the primary indication and neurodegenerative conditions such as Parkinson’s disease as secondary indications,” says Eric Konofal, MD, PhD, chief scientific officer of NLS Pharmaceutics, president of Aexon Labs, and inventor of the dual orexin receptor agonist platform. “This application highlights the continued commitment from NLS to pioneer therapeutic approaches to address significant unmet medical needs.”

Key Highlights:

  • Dual Orexin Receptor Agonists: The patent application introduces a 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 non-sulfonamide derivatives have the potential to reduce the risk of side effects and adverse reactions associated with traditional sulfonamide medications, according to a release from NLS, which notes that 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 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 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.
  • 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. 

Recent Advances and Presentations

At SLEEP 2024, 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, 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, according to a release from NLS.

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