NLS Pharmaceutics Announces Promising Preclinical Data for First-in-Class Non-Sulfonamide, Dual Orexin Receptor Agonists for the Potential Treatment of Narcolepsy and Neurological Disorders
NLS Pharmaceutics (NASDAQ:NLSP) announced promising preclinical data for its dual orexin receptor agonist (DOXA) platform. The study focuses on AEX-41 and AEX-2, first-in-class non-sulfonamide DOXAs targeting both orexin-1 and orexin-2 receptors while inhibiting cathepsins. In orexin knockout mice, AEX-41 showed significant increase in wakefulness and reduced REM sleep duration, with efficacy comparable to existing OX2R agonists. The company plans to expand research in 2025 to study neuroinflammation impact, with an IND application planned for 2026-2027. The dual-action mechanism could potentially address both sleep-wake regulation and neurodegenerative processes.
NLS Pharmaceutics (NASDAQ:NLSP) ha annunciato dati preclinici promettenti per la sua piattaforma di agonisti del recettore dell'orexina duali (DOXA). Lo studio si concentra su AEX-41 e AEX-2, agonisti di prima classe non sulfonamidici che colpiscono sia i recettori orexina-1 che orexina-2, oltre a inibire le catepsine. Nei topi privi di orexina, AEX-41 ha mostrato un aumento significativo della vigilanza e una riduzione della durata del sonno REM, con un'efficacia paragonabile a quella degli agonisti OX2R esistenti. L'azienda prevede di ampliare la ricerca nel 2025 per studiare l'impatto della neuroinfiammazione, con una richiesta IND pianificata per il 2026-2027. Il meccanismo d'azione duale potrebbe affrontare potenzialmente sia la regolazione del sonno e della veglia sia i processi neurodegenerativi.
NLS Pharmaceutics (NASDAQ:NLSP) anunció datos preclínicos prometedores para su plataforma de agonistas duales de los receptores de orexina (DOXA). El estudio se centra en AEX-41 y AEX-2, agonistas de primera clase no sulfonamídicos dirigidos a los receptores de orexina-1 y orexina-2, mientras inhiben la catepsina. En ratones knock-out de orexina, AEX-41 mostró un aumento significativo de la vigilia y una reducción en la duración del sueño REM, con una eficacia comparable a la de los agonistas OX2R existentes. La compañía planea expandir la investigación en 2025 para estudiar el impacto de la neuroinflamación, con una solicitud IND prevista para 2026-2027. El mecanismo de acción dual podría abordar potencialmente tanto la regulación del sueño y la vigilia como los procesos neurodegenerativos.
NLS Pharmaceutics (NASDAQ:NLSP)는 이중 오렉신 수용체 작용제(DOXA) 플랫폼에 대한 유망한 전임상 데이터를 발표했습니다. 이 연구는 오렉신-1과 오렉신-2 수용체를 타겟으로 하고 카테핀을 억제하는 첫 번째 클래스의 비술폰아마이드 DOXA인 AEX-41 및 AEX-2에 초점을 맞추고 있습니다. 오렉신 유전자 결손 마우스에서 AEX-41은 각성의 유의미한 증가와 REM 수면 시간의 감소를 보여주었으며, 기존 OX2R 작용제와 비슷한 효능을 보였습니다. 이 회사는 2025년에 신경 염증 영향을 연구하기 위해 연구를 확장할 계획이며, 2026-2027년에 IND 신청을 예정하고 있습니다. 이중 작용 메커니즘은 수면-각성 조절과 신경퇴행성 과정 모두를 해결할 잠재력이 있습니다.
NLS Pharmaceutics (NASDAQ:NLSP) a annoncé des données précliniques prometteuses pour sa plateforme d'agonistes des récepteurs d'orexine double (DOXA). L'étude se concentre sur AEX-41 et AEX-2, des agonistes de première classe non sulfonamides ciblant à la fois les récepteurs d'orexine-1 et d'orexine-2 tout en inhibant les cathepsines. Chez les souris knock-out d'orexine, AEX-41 a montré une augmentation significative de l'éveil et une réduction de la durée de sommeil REM, avec une efficacité comparable à celle des agonistes OX2R existants. L'entreprise prévoit d'élargir ses recherches en 2025 pour étudier l'impact de la neuroinflammation, avec une demande IND prévue pour 2026-2027. Le mécanisme d'action dual pourrait potentiellement aborder à la fois la régulation du sommeil et de l'éveil et les processus neurodégénératifs.
NLS Pharmaceutics (NASDAQ:NLSP) hat vielversprechende präklinische Daten für seine Plattform von dualen Orexin-Rezeptor-Agonisten (DOXA) veröffentlicht. Die Studie konzentriert sich auf AEX-41 und AEX-2, erstklassige nicht-sulfonamidische DOXAs, die sowohl die Orexin-1- als auch die Orexin-2-Rezeptoren ansprechen und gleichzeitig Cathepsine hemmen. Bei Orexin-Knockout-Mäusen zeigte AEX-41 ein signifikantes Plus an Wachsamkeit und eine reduzierte REM-Schlafdauer, mit einer Wirksamkeit, die mit bestehenden OX2R-Agonisten vergleichbar ist. Das Unternehmen plant, 2025 die Forschung zu erweitern, um die Auswirkungen von Neuroinflammation zu untersuchen, wobei eine IND-Antrag für 2026-2027 geplant ist. Der duale Wirkmechanismus könnte potenziell sowohl die Schlaf-Wach-Regulation als auch neurodegenerative Prozesse ansprechen.
- Successful preclinical results showing significant increase in wakefulness
- AEX-41 demonstrated efficacy comparable to existing OX2R agonists
- Novel dual-action mechanism targeting both orexin receptors and cathepsins
- IND application not planned until 2026-2027, indicating lengthy development timeline
- Early-stage preclinical data with no human trials yet
Insights
The preclinical data for NLS Pharmaceutics' dual orexin receptor agonists (DOXAs) represents a significant scientific advancement in narcolepsy treatment. The compounds AEX-41 and AEX-2 show promising results through their novel non-sulfonamide approach and dual-targeting mechanism.
The data demonstrates two key advantages: First, AEX-41's efficacy matches existing OX2R agonists while offering a potentially safer non-sulfonamide structure. Second, the dual-action mechanism targeting both orexin receptors and cathepsin inhibition could provide both symptomatic relief and disease modification - a significant improvement over current treatments that only address symptoms.
However, investors should note that this is still early-stage research, with IND filing planned for 2026-2027. The timeline to potential commercialization is lengthy and success in preclinical studies doesn't guarantee clinical trial success. The market opportunity is substantial though, as current narcolepsy treatments have limitations and there's potential expansion into other neurological disorders.
ZÜRICH, SWITZERLAND / ACCESSWIRE / December 3, 2024 / NLS Pharmaceutics Ltd. (NASDAQ:NLSP)(NASDAQ:NLSPW) (NLS), a biopharmaceutical company, is pleased to share preclinical data demonstrating the potential of its dual orexin receptor agonist (DOXA) platform. AEX-41 and AEX-2, two first-in-class non-sulfonamide DOXAs, are designed to target both orexin-1 (OX1R) and orexin-2 (OX2R) 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 (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.
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 (CTSH) 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 (IND) application is planned for 2026-2027 to support this new avenue of study.
Eric Konofal, MD, PhD, Chief Scientific Officer of NLS and inventor of the DOXA platform, stated, "The dual mechanism of AEX-41 marks a transformative approach in treating narcolepsy. By simultaneously targeting orexin receptors and cathepsins, we aim to provide both symptomatic relief and disease-modifying potential- which would be an advancement over current therapies. In addition, based on cathepsins broad mechanism of action, we believe the DOXA platform may hold significant synergies with Kadimastem's pipeline, especially in the areas of diabetes, which is often associated with sleep-wake dysregulation manifesting as insomnia, as well as amyotrophic lateral sclerosis. ″
NLS is actively advancing the development of AEX-41 and AEX-2, with plans to further evaluate their safety and efficacy in clinical settings. Beyond narcolepsy, the company is exploring their potential application in other neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS), leveraging their unique dual-targeting mechanism.
About Narcolepsy
Narcolepsy is a lifelong sleep disorder caused by the autoimmune-mediated loss of 70,000-90,000 orexin-producing neurons in the hypothalamus. It is characterized by excessive daytime sleepiness, cataplexy, and rapid eye movement sleep abnormalities, and is tightly associated with the human leukocyte antigen HLA-DQB1*06:02. Other predisposing factors for narcolepsy include associations with polymorphisms in the T-cell receptor alpha and beta genes, whose products recognize antigens presented by HLA molecules, and the CTSH gene.
About NLS Pharmaceutics Ltd.
NLS Pharmaceutics is a global biopharmaceutical company dedicated to developing innovative therapies for rare and complex central nervous system disorders. With a robust pipeline targeting narcolepsy, idiopathic hypersomnia, and neurodegenerative diseases, NLS is committed to addressing unmet medical needs.
For more information, visit nlspharmaceutics.com
Safe Harbor Statement
This press release contains expressed or implied forward-looking statements pursuant to U.S. Federal securities laws. For example, NLS is using forward-looking statements when it discusses the DOXA platform, the potential safety and efficacy of AEX-41 and AEX-2, plans to expand its research and timing thereof, potential submission of an IND and NLS' pipeline. These forward-looking statements and their implications are based on the current expectations of the management of NLS only and are subject to a number of factors and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. The following factors, among others, could cause actual results to differ materially from those described in the forward-looking statements: changes in technology and market requirements; NLS may encounter delays or obstacles in launching and/or successfully completing its clinical trials; NLS products may not be approved by regulatory agencies, NLS technology may not be validated as it progresses further and its methods may not be accepted by the scientific community; NLS may be unable to retain or attract key employees whose knowledge is essential to the development of its products; unforeseen scientific difficulties may develop with NLS' process; NLS' products may wind up being more expensive than it anticipates; results in the laboratory may not translate to equally good results in real clinical settings; results of preclinical studies may not correlate with the results of human clinical trials; NLS patents may not be sufficient; NLS products may harm recipients; changes in legislation may adversely impact NLS; inability to timely develop and introduce new technologies, products and applications; and loss of market share and pressure on pricing resulting from competition, which could cause the actual results or performance of NLS to differ materially from those contemplated in such forward-looking statements. Except as otherwise required by law, NLS undertakes no obligation to publicly release any revisions to these forward-looking statements to reflect events or circumstances after the date hereof or to reflect the occurrence of unanticipated events. More detailed information about the risks and uncertainties affecting NLS is contained under the heading "Risk Factors" in NLS annual report on Form 20-F for the year ended December 31, 2023 filed with the Securities and Exchange Commission (SEC), which is available on the SEC's website, www.sec.gov, and in subsequent filings made by NLS with the SEC.
Contact Information
Investor Relations Contact:
InvestorRelations@nls-pharma.com
SOURCE: NLS Pharmaceutics AG
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FAQ
What were the key preclinical results for NLSP's AEX-41 in narcolepsy treatment?
When does NLSP plan to file an IND application for their DOXA platform?
What is unique about NLSP's DOXA platform mechanism of action?
