NLS Pharmaceutics Announces New Preclinical Data for AEX-2, Expanding the Therapeutic Potential of its Non-Sulfonamide Dual Orexin Receptor Agonist Platform
NLS Pharmaceutics (NLSP) has announced new preclinical findings for AEX-2, their non-sulfonamide dual orexin receptor agonist (DOXA). The research demonstrates promising results in treating narcolepsy and related neurological disorders.
Key findings from preclinical studies show that AEX-2 (20 mg/kg, IP) significantly enhanced wakefulness while maintaining stable wake architecture, preserved REM sleep patterns, and effectively reduced cataplexy episodes in narcolepsy type 1.
The company is expanding its therapeutic potential beyond sleep disorders, with AEX-2 and AEX-41 showing promise in treating neuroinflammation, ALS, Parkinson's disease, and diabetes-associated neurological disorders through Sigma-1 receptor modulation. NLS plans to advance both compounds into IND-enabling studies in 2025, targeting first-in-human clinical trials by 2026.
NLS Pharmaceutics (NLSP) ha annunciato nuove scoperte precliniche per AEX-2, il loro agonista duale dei recettori orexina non sulfonamidico (DOXA). La ricerca dimostra risultati promettenti nel trattamento della narcolessia e dei disturbi neurologici correlati.
I risultati chiave degli studi preclinici mostrano che AEX-2 (20 mg/kg, IP) ha migliorato significativamente la vigilanza mantenendo un'architettura del sonno stabile, preservando i modelli di sonno REM e riducendo efficacemente gli episodi di cataplessia nella narcolessia di tipo 1.
L'azienda sta ampliando il suo potenziale terapeutico oltre i disturbi del sonno, con AEX-2 e AEX-41 che mostrano promesse nel trattamento della neuroinfiammazione, della SLA, del morbo di Parkinson e dei disturbi neurologici associati al diabete attraverso la modulazione del recettore Sigma-1. NLS prevede di portare entrambi i composti in studi abilitanti IND nel 2025, puntando a trial clinici di prima in umani entro il 2026.
NLS Pharmaceutics (NLSP) ha anunciado nuevos hallazgos precl铆nicos para AEX-2, su agonista dual de los receptores de orexina no sulfonam铆dico (DOXA). La investigaci贸n demuestra resultados prometedores en el tratamiento de la narcolepsia y los trastornos neurol贸gicos relacionados.
Los hallazgos clave de los estudios precl铆nicos muestran que AEX-2 (20 mg/kg, IP) mejor贸 significativamente la vigilia mientras manten铆a una arquitectura del sue帽o estable, preservaba los patrones de sue帽o REM y reduc铆a eficazmente los episodios de cataplej铆a en la narcolepsia tipo 1.
La empresa est谩 ampliando su potencial terap茅utico m谩s all谩 de los trastornos del sue帽o, con AEX-2 y AEX-41 mostrando promesas en el tratamiento de la neuroinflamaci贸n, la ELA, la enfermedad de Parkinson y los trastornos neurol贸gicos asociados con la diabetes a trav茅s de la modulaci贸n del receptor Sigma-1. NLS planea avanzar ambos compuestos a estudios habilitantes IND en 2025, con el objetivo de ensayos cl铆nicos en humanos para 2026.
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NLS Pharmaceutics (NLSP) a annonc茅 de nouvelles d茅couvertes pr茅cliniques concernant AEX-2, leur agoniste dual des r茅cepteurs d'orexine non sulfonamide (DOXA). La recherche d茅montre des r茅sultats prometteurs dans le traitement de la narcolepsie et des troubles neurologiques associ茅s.
Les r茅sultats cl茅s des 茅tudes pr茅cliniques montrent qu'AEX-2 (20 mg/kg, IP) a consid茅rablement am茅lior茅 l'茅veil tout en maintenant une architecture de sommeil stable, pr茅servant les sch茅mas de sommeil REM et r茅duisant efficacement les 茅pisodes de cataplexie dans la narcolepsie de type 1.
L'entreprise 茅largit son potentiel th茅rapeutique au-del脿 des troubles du sommeil, avec AEX-2 et AEX-41 montrant des promesses dans le traitement de la neuroinflammation, de la SLA, de la maladie de Parkinson et des troubles neurologiques associ茅s au diab猫te gr芒ce 脿 la modulation du r茅cepteur Sigma-1. NLS pr茅voit de faire progresser les deux compos茅s vers des 茅tudes d'habilitation IND en 2025, visant des essais cliniques chez l'homme d'ici 2026.
NLS Pharmaceutics (NLSP) hat neue pr盲klinische Ergebnisse f眉r AEX-2 bekannt gegeben, ihren nicht-sulfonamidischen dualen Orexin-Rezeptor-Agonisten (DOXA). Die Forschung zeigt vielversprechende Ergebnisse bei der Behandlung von Narkolepsie und verwandten neurologischen St枚rungen.
Wichtige Ergebnisse aus pr盲klinischen Studien zeigen, dass AEX-2 (20 mg/kg, IP) die Wachsamkeit signifikant verbessert hat, w盲hrend die Wacharchitektur stabil blieb, REM-Schlafmuster erhalten blieben und die Kataplexie-Episoden bei Narkolepsie Typ 1 effektiv reduziert wurden.
Das Unternehmen erweitert sein therapeutisches Potenzial 眉ber Schlafst枚rungen hinaus, wobei AEX-2 und AEX-41 vielversprechende Ans盲tze zur Behandlung von Neuroinflammation, ALS, Parkinson und diabetesassoziierten neurologischen St枚rungen durch die Modulation des Sigma-1-Rezeptors zeigen. NLS plant, beide Verbindungen 2025 in IND-f盲hige Studien voranzutreiben, mit dem Ziel, bis 2026 klinische Studien am Menschen zu beginnen.
- Successful preclinical results showing efficacy in narcolepsy treatment
- Expanded therapeutic potential beyond sleep disorders
- Multi-target mechanism addressing multiple diseases
- Clear development timeline with IND studies in 2025
- Potential competitive advantage over existing treatments with safety concerns
- Still in early preclinical stage
- No human trial data available yet
- Clinical trials won't start until 2026
Insights
The preclinical results for AEX-2 represent a meaningful advancement in orexin receptor-targeting therapeutics. Unlike sulfonamide-based orexin agonists that have shown safety limitations (like TAK-994), NLS's non-sulfonamide DOXA platform potentially offers a safer alternative while demonstrating three key pharmacodynamic effects: enhanced wakefulness without fragmentation, preserved REM sleep architecture, and reduced cataplexy episodes.
What's scientifically significant is AEX-2's multi-target mechanism beyond just orexin receptor activation. The engagement with Sigma-1 receptors is particularly noteworthy as these receptors regulate neuroprotection and synaptic plasticity. This dual mechanism creates a broader therapeutic profile that could address both symptom management (sleep-wake disruption) and underlying neurological processes (neuroinflammation).
The expansion into diabetes-associated neurological disorders (DANS) makes mechanistic sense given orexin's role in metabolic regulation. However, these findings remain preclinical (20 mg/kg IP dosing in mice), and translational challenges from mouse models to humans are substantial. The timeline to IND-enabling studies in 2025 and first-in-human trials by 2026 follows standard development pathways but represents a long horizon before potential clinical application. The upcoming ASCP presentation in May will likely provide more detailed efficacy and selectivity data needed to fully evaluate this compound's potential.
These preclinical findings substantially expand NLS Pharmaceutics' addressable market potential by positioning their DOXA platform beyond narcolepsy into broader neurological and metabolic conditions. For a company with
The multi-target profile differentiates NLS's approach from competitors like Takeda's orexin receptor agonists, which have reportedly faced safety challenges. If AEX-2's non-sulfonamide structure indeed offers a better safety profile while maintaining efficacy, it could potentially capture significant market share in the narcolepsy space while opening doors to neurodegenerative indications like ALS and Parkinson's鈥攎uch larger markets with substantial unmet needs.
The collaboration with Aexon Labs brings computational chemistry and AI-driven optimization capabilities that appear to have yielded compounds with promising blood-brain barrier penetration and receptor selectivity profiles. However, investors should note that the timeline to potential commercialization remains lengthy, with IND-enabling studies in 2025 and human trials not beginning until 2026. The critical inflection points will be IND filing, transition to clinical development, and eventual proof-of-concept in humans鈥攁ll carrying substantial technical risk. While the expanded therapeutic applications create a more robust development pathway, the early stage of these compounds warrants careful risk assessment.
窜脺搁滨颁贬,
Key Preclinical Findings on AEX-2 (20 mg/kg, IP)
Recent preclinical advancements have demonstrated the multi-target potential of DOXA compounds, including AEX-41 and AEX-2, in redefining sleep-wake regulation and neuroprotection. In orexin-deficient mouse models, these compounds exhibited strong wake-promoting effects and sleep-wake cycle stabilization, reinforcing their potential as next-generation therapeutics. Key findings include:
- Wakefulness Enhancement: AEX-2 significantly increased total wake duration while maintaining a stable wake architecture, avoiding excessive fragmentation.
- REM Sleep Preservation: Unlike traditional stimulants, AEX-2 regulated rapid eye movement ("REM") sleep dynamics, minimizing undesired suppression and sleep rebound effects.
- Reduction in Cataplexy: AEX-2 effectively reduced the frequency and duration of cataplexy episodes, a crucial advancement for treating narcolepsy type 1 (NT1).
These data underscore the potential of AEX-2 as a safer and more targeted alternative to existing orexin-based therapies, such as TAK-994 and TAK-861, which have been hindered by safety concerns.
Expanding the AEX Platform: AEX-2 and AEX-41 in Neurodegeneration and Metabolic Disorders
Beyond narcolepsy, NLS Pharmaceutics and Aexon Labs are advancing AEX-2 and AEX-41 into new therapeutic areas, leveraging their multi-target mechanisms that extend to neuroinflammatory and metabolic pathways.
- 罢补谤驳别迟颈苍驳听狈别耻谤辞颈苍蹿濒补尘尘补迟颈辞苍: Recent discoveries highlight AEX compounds' engagement with the Sigma-1 receptor, which plays a key role in neuroprotection, synaptic plasticity, and REM sleep regulation.
- Potential in ALS and Neurodegenerative Diseases: Sigma-1 receptor modulation, combined with orexin receptor activation, suggests AEX-41 may have applications in ALS and Parkinson's disease, particularly in preserving motor function and reducing neuroinflammation.
- Addressing Diabetes-Associated Neurological Disorders ("DANS"): Given the link between orexin signalling, metabolic regulation, and sleep disorders, the multi-target properties of DOXA compounds such as AEX-2 and AEX-41 could provide new therapeutic avenues for diabetes-related neuropathy and cognitive decline.
Aexon Labs, known for its cutting-edge computational chemistry and AI-driven drug discovery, has played a key role in optimizing these multi-target molecules, ensuring high blood-brain barrier penetration and selective receptor affinity.
Future Directions: Unlocking Multi-target Potential
Building on these breakthrough findings, NLS Pharmaceutics is advancing AEX-2 and AEX-41 into IND-enabling studies in 2025, targeting first-in-human clinical trials by 2026.
Beyond dual orexin receptor activation, these compounds engage Sigma-1 receptor modulation, cathepsin inhibition, and mitochondrial regulation, reinforcing their first-in-class potential.
To validate this multi-target strategy, additional preclinical studies are underway, including an ongoing DANS model, potentially broadening their applications beyond sleep disorders.
"The recent preclinical findings represent a key milestone for our DOXA platform,"聽said聽Eric Konofal, MD, PhD, Chief Scientific Officer of NLS Pharmaceutics.聽"These preliminary findings reinforce our commitment to developing neurodegenerative therapies that not only manage symptoms, but also address the underlying mechanisms of sleep and neurodegenerative disorders. With ongoing studies in DANS, we are further expanding the potential of our multitarget approach to address metabolic dysfunction and its impact on brain health."
"We are encouraged by these recent preclinical results, which showcase the unique potential of our DOXA platform," said Alex Zwyer, CEO of NLS Pharmaceutics. "We believe these findings not only strengthen our commitment to developing transformative neurodegenerative therapies, but they also highlight the importance of addressing the underlying mechanisms associated with sleep and neurodegenerative disorders. As we continue our studies in DANS, we are optimistic about expanding the therapeutic landscape of our multi-target approach."
NLS Pharmaceutics plans to present the definitive results on AEX-2 and AEX-41 at the American Society for Clinical Psychopharmacology (ASCP) Annual Meeting, taking place May 27-30, 2025, at the Fairmont Scottsdale Princess in
About Aexon Labs
Aexon Labs is a聽cutting-edge biotechnology company聽specializing in聽intelligente drug discovery and computational chemistry聽to develop聽next-generation therapeutics聽for聽sleep disorders, neurodegenerative diseases, and metabolic dysfunctions. Leveraging聽advanced molecular modeling and multi-target drug design, Aexon Labs is at the forefront of聽innovative compound development, integrating聽dual orexin receptor activation, neuroinflammation modulation, and mitochondrial regulation.
With a聽strong focus on translational research, Aexon Labs is dedicated to pioneering聽first-in-class therapies, including its聽non-sulfonamide dual orexin receptor agonist (DOXA) platform, designed to聽restore sleep-wake balance, enhance neuroprotection, and improve metabolic homeostasis.
For more information, visit聽.
About NLS Pharmaceutics
NLS Pharmaceutics is a global biopharmaceutical company聽focused on developing聽next-generation therapies聽for聽sleep disorders, neurodegenerative diseases, and metabolic dysfunctions. Through a聽strategic licensing agreement with Aexon Labs, NLS is advancing a portfolio of聽non-sulfonamide dual orexin receptor agonists (DOXA), including聽AEX-2 and AEX-41, designed to聽restore sleep-wake balance, reduce neuroinflammation, and address metabolic dysregulation.
Forward-Looking Statements
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FAQ
What are the key preclinical results of NLSP's AEX-2 for narcolepsy treatment?
When will NLSP begin human clinical trials for AEX-2 and AEX-41?
What additional therapeutic areas is NLSP targeting with AEX-2 and AEX-41?
Where will NLSP present the definitive results for AEX-2 and AEX-41?
How does NLSP's AEX platform differ from existing orexin-based therapies?
