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 Z rich, Switzerland

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

Z rich, Switzerland, December 3, 2024 -

NLS Pharmaceutics Ltd. (Nasdaq: NLSP, 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:

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

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.

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