Dual-Action Drug Candidates Show Promise for Narcolepsy and Beyond
Zurich, Switzerland – December 3, 2024 – NLS Pharmaceutics Ltd. (NASDAQ:NLSP) (NASDAQ:NLSPW) (NLS), a biopharmaceutical company dedicated to developing innovative therapies for complex neurological disorders, announces promising preclinical data for its dual orexin receptor agonist (DOXA) platform. Two first-in-class non-sulfonamide DOXAs, AEX-41 and AEX-2, show potential in targeting both orexin-1 (OX1R) and orexin-2 (OX2R) receptors, potentially offering a novel therapeutic approach for narcolepsy and other neurological disorders.
**A Multi-Layered Approach to Neurological Challenges
** The preclinical study, initiated in October 2024 at the Centre for Neuroscience Research of Lyon, one of Europe’s leading neuroscience research centers, yielded compelling findings.
Key Preclinical Results:
- Enhanced Wakefulness and Optimized Sleep: In mice models missing the gene responsible for producing orexin, AEX-41 (administered orally at 40 mg/kg) demonstrated a significant increase in wakefulness and a reduction in REM sleep duration. These effects are crucial for managing the core symptoms of narcolepsy, a chronic sleep disorder characterized by excessive daytime sleepiness, sudden sleep episodes, and sometimes paralysis.
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Comparable Efficacy to Existing Therapies: The efficacy of AEX-41 was comparable to sulfonamide-derivative selective OX2R agonists under similar experimental conditions, marking its potential as a versatile alternative for broader therapeutic applications.
- Targeting Multiple Pathways for Broader Impact:
AEX-41 stands out for its dual-action mechanism. By targeting both orexin recipients and inhibiting Cathepsin H (CTSH) activity, the molecule offers a more comprehensive approach to neurodegenerative disorders.
**Expanding Research Horizons:
дельник, 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. A pivotal step in advancing this promising platform is filing an Investigational New Drug (IND) application scheduled for 2026-2027.
"[This research] marks a transformative approach in treating narcolepsy," stated Dr. Eric Konofal, Chief Scientific Officer of NLS and inventor of the DOXA platform. "By simultaneously targeting orexin receptors and cathepsins, we aim to provide both symptomatic relief and disease-modifying potential – a significant advancement over current therapies. Additionally, based on cathepsins’ broad mechanisms of action, we believe the DOXA platform may hold synergies with existing pipelines, particularly in attacking diabetes (often linked to sleep-wake disruption including insomnia), and amyotrophic lateral sclerosis."
**Beyond Narcolepsy:
** NLS is actively advancing both AEX-41 and AEX-2 toward clinical evaluation. Beyond addressing narcolepsy, the thriving neurodegenerative disease pipeline includes idiopathic hypersomnia and ALS. This unique dual-targeting approach addresses a much broader unmet medical need.
**About
NLS Pharmaceutics Ltd.:
** NLS is a global biopharmaceutical company dedicated to finding innovative therapies for rare and complex central nervous system disorders. Guided by a powerful pipeline targeting narcolepsy, idiopathic hypersomnia, and neurodegenerative diseases, NLS tirelessly works towards sustainably addressing the unmet needs of patients globally.
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When can we expect to see human trials for AEX-41?
## Promising New Drug Shows Potential for Treating Narcolepsy and Beyond
**Interviewer:** Welcome to the program. Today we’re discussing exciting new research from NLS Pharmaceutics regarding a potential treatment for narcolepsy and other neurological disorders. We’re joined by Dr. [Guest’s Name], a [Guest’s Credentials] specializing in [Guest’s Specialty]. Dr. [Guest Name], thank you for joining us.
**Dr. [Guest Name]:** It’s a pleasure to be here.
**Interviewer:** Can you tell us about this new drug candidate and how it works?
**Dr. [Guest Name]:** NLS Pharmaceutics is developing a class of drugs called dual orexin receptor agonists, or DOXAs. These drugs target orexin receptors in the brain. Orexin is a neuropeptide that plays a crucial role in regulating wakefulness, arousal, and appetite. [ [1](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9465891/) ]In individuals with narcolepsy, the brain cells that produce orexin are lost, leading to the symptoms they experience.
**Interviewer:** So, directly targeting these receptors could potentially alleviate those symptoms?
**Dr. [Guest Name]:** Exactly. Their lead candidate, AEX-41, has shown promising results in preclinical studies. When tested on mice models missing the gene responsible for orexin production, AEX-41 significantly increased wakefulness and reduced REM sleep duration, key factors for managing narcolepsy.
**Interviewer:** That’s fascinating. Are there other potential benefits beyond treating narcolepsy?
**Dr. [Guest Name]:** That’s one of the exciting things about AEX-41. It not only targets orexin receptors but also inhibits Cathepsin H activity. This dual-action mechanism opens up possibilities for treating a wider range of neurological disorders.
**Interviewer:** Can you elaborate on that?
**Dr. [Guest Name]:** Cathepsin H is an enzyme implicated in neurodegenerative diseases. By inhibiting its activity, AEX-41 could potentially slow or even prevent the progression of conditions like Alzheimer’s disease or Parkinson’s disease.
**Interviewer:** This is truly groundbreaking research. When can we expect to see human trials for AEX-41?
**Dr. [Guest Name]:** NLS Pharmaceutics is currently working towards initiating Phase I clinical trials in the near future, which will provide valuable insights into the safety and efficacy of AEX-41 in humans.
**Interviewer:** Thank you, Dr. [Guest Name], for sharing this exciting news with us. We eagerly await the results of the clinical trials and the potential impact this drug could have on the lives of millions.
