ZÜRICH, Switzerland, Feb. 27,
2025 /PRNewswire/ -- NLS Pharmaceutics Ltd. (Nasdaq:
NLSP) (Nasdaq: NLSPW) ("NLS" or the "Company"), in collaboration
with Aexon Labs Inc. ("Aexon Labs"), is pleased to announce new
preclinical findings on AEX-2, reinforcing its potential as a
first-in-class non-sulfonamide dual orexin receptor agonist
("DOXA") for narcolepsy and related neurological disorders. These
results build upon the Company's multi-target neurodegenerative
strategy, which also includes AEX-41, demonstrating a novel and
promising approach to addressing sleep disorders,
neuroinflammation, and metabolic dysfunction.
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.
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," said Eric Konofal, MD, PhD, Chief
Scientific Officer of NLS Pharmaceutics. "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 Scottsdale, Arizona.
NLS Pharmaceutics' poster presentation titled "Non-Sulfonamide Dual
Orexin Receptor Agonists: Preliminary Results of AEX-41 and AEX-2
in a Mouse Model," will be displayed on May
27-30, 2025.
About Aexon Labs
Aexon Labs is a cutting-edge biotechnology
company specializing in intelligente drug discovery and
computational chemistry to develop next-generation
therapeutics for sleep disorders, neurodegenerative
diseases, and metabolic dysfunctions. Leveraging advanced
molecular modeling and multi-target drug design, Aexon Labs is at
the forefront of innovative compound development,
integrating dual orexin receptor activation, neuroinflammation
modulation, and mitochondrial regulation.
With a strong focus on translational research, Aexon Labs
is dedicated to pioneering first-in-class therapies, including
its non-sulfonamide dual orexin receptor agonist (DOXA)
platform, designed to restore sleep-wake balance, enhance
neuroprotection, and improve metabolic homeostasis.
For more information, visit www.aexonlabs.com.
About NLS Pharmaceutics
NLS Pharmaceutics is a global biopharmaceutical
company focused on developing next-generation
therapies for sleep disorders, neurodegenerative
diseases, and metabolic dysfunctions. Through a strategic
licensing agreement with Aexon Labs, NLS is advancing a portfolio
of non-sulfonamide dual orexin receptor agonists (DOXA),
including AEX-2 and AEX-41, designed to restore
sleep-wake balance, reduce neuroinflammation, and address metabolic
dysregulation. www.nlspharma.com
Forward-Looking Statements
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, the development and potential applications of
AEX-41 and AEX02 and timing thereof, plans to expand its research
and timing thereof, 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.
NLS Contacts:
InvestorRelations@nls-pharma.com
www.nlspharma.com
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