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.

Targeting Neuroinflammation: 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

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