Z rich, Switzerland

Z rich, Switzerland, December 29, 2023 - NLS Pharmaceutics

Ltd. (Nasdaq: NLSP, NLSPW) ("NLS" or the "Company"), a Swiss clinical-stage biopharmaceutical company, focused on

the discovery and development of innovative therapies for patients with rare and complex central nervous system disorders, today announces

that its Chief Executive Officer, Alex Zwyer, has issued the following letter to shareholders:

NLS Pharmaceutics CEO Issues Letter to Shareholders

To our Shareholders and Friends,

In 2023, there were significant challenges both within the healthcare

sector and around the globe, from the ongoing wars in Ukraine and the Middle East, adjusting to a post-pandemic world, to growing geopolitical

tensions and widespread political division. Closer to home, biotech financing was more challenging than ever as all types of financing

decreased dramatically versus previous years. All of these have had serious consequences on our company, our colleagues, and most importantly,

you, our shareholders.

As you have continued to support the advancement of our pipeline in

rare sleep disorders and other rare and debilitating Central Nervous System (CNS) disorders, I wanted to take a moment to report on the

progress that we have made as well as the challenges we have sustained.

At the start of 2023, we outlined our objectives

for the year, which included:

Despite many challenges, we have delivered on

many of these as well as other accomplishments, including partaking in numerous investor conference presentations, medical congresses,

additions of crucial leadership positions, key opinion leader events, and more. As we near the end of 2023 and close out this challenging

year, I wanted to take the opportunity to share the progress that we have made, which we could not have achieved without your help.

Earlier this year, we reported on positive full

results from the Phase 2 clinical trial (NLS-1021) and open-label extension (NLS-1022) evaluating our lead product candidate, Mazindol

ER, in the treatment of narcolepsy. The trial met its primary endpoint with high statistical significance, demonstrating the efficacy,

tolerability, and safety of the treatment. These exciting results were presented at SLEEP 2023 in Indianapolis, the annual meeting of

the American Academy of Sleep Medicine (AASM) and the Sleep Research Society (SRS).

Despite not initially receiving fast-track designation,

the request can be reinitiated at any time during the drug development process and therefore may be resubmitted following the completion

of the next phase of development. Fast track is a process designed to facilitate the development and expedite the review of drugs to treat

serious conditions and fill an unmet medical need, getting important new drugs to the patient earlier.

In July 2023, NLS announced that the Phase 3 clinical

trial (which we call the AMAZE Program) protocol to evaluate the safety and efficacy of Mazindol ER in patients with narcolepsy type 1

received approval from the independent Institutional Review Board (IRB). The AMAZE Program encompasses two almost-identical double-blind

Phase 3 studies (N=50 each) investigating Mazindol ER versus placebo in adult patients with narcolepsy. Along with IRB approval and the

green light from the FDA, NLS has retained a contract research organization (CRO) and has enrolled a number of sites for the phase 3 studies.

Once suitable capital has been secured, we expect the phase 3 program to commence as the sites are ready to begin enrolling patients.

Ongoing Business Development

Earlier this month, it was announced that NLS

had entered into an exclusive worldwide option agreement with Aexon Labs, Inc., a privately held U.S. company ("Aexon

Labs"), under which NLS may acquire global development and commercialization rights to Aexon Labs' Dual Orexin Receptor

Agonists platform, new molecular entities, highly selective dual oral orexin-1 and orexin-2 receptor agonists (OX1R and OX2R) with

potential applications in the treatment of narcolepsy and idiopathic hypersomnia, as well as neuro-degenerative disorders such as

Parkinson's and Alzheimer's disease. This option agreement represents a potentially leading next-generation,

first-in-class, oral, dual orexin receptor agonist platform that is expected to address high unmet medical needs and has shown

promising results in pre-clinical in vitro assays. Aexon Labs has plans to initiate proof-of-concept preclinical development in

The possibility to acquire

this novel and unique platform, consisting of over 300 compounds, bridges the present to the future treatment of sleep disorders as well

as other neuro-degenerative disorders. Orexin receptor pathways play vital regulatory roles in many physiological processes and studies

have shown that orexin receptor pathways are involved in pathological processes of neurological diseases such as obesity, narcolepsy,

depression, ischemic stroke, drug addiction and Alzheimer's disease. These new compounds, in addition to our current pipeline, including

Mazindol ER for the treatment of narcolepsy, NLS-4 focused on idiopathic hypersomnia, long-COVID and chronic fatigue syndrome, and NLS-11,

addressing Kleine-Levin Syndrome and neurodegenerative diseases, will further complement and strengthen our sleep franchise. NLS will

be uniquely positioned to hold the key to unlock the challenges associated with rare sleep disorders now and in the future.

In addition, NLS has

initiated a comprehensive exploration of new opportunities that align with its core values and strengths, with the goal of diversifying

NLS revenue streams, mitigating risks and creating lasting value for our stakeholders. As part of this process, the Company is considering

a wide range of options with a focus on maximizing shareholder value, including strategic partnerships, out licensing assets of the Company,

and other future strategic actions. Several strategic partnerships discussions are currently under way and in advanced stages of negotiations.

As always, we continue to approach the sleep medicine market from a holistic perspective. The Global Sleep Medicine Market is estimated

to increase to more than $100 Billion by 2030, with narcolepsy accounting for over $6 billion by 2030.

In August of this year, we announced the appointment of Elena Thyen-Pighin

to the position of Chief Financial Officer (CFO) & Head of Finance / Human Resources. Ms. Thyen-Pighin has extensive experience in

leadership and management functions as both head of finance and human resources across several industries, including organizations similar

to NLS. Based in Switzerland, Ms. Thyen-Pighin speaks 5 languages and has a strong and successful track record, most notably in accounting

for both private and publicly listed enterprises.

Additionally, NLS announced in November the appointment

of Dr. Florence Allouche Aknin and Dr. Claudio Bassetti to join the Board of Directors effective January 1, 2024.

Professor Bassetti's vast leadership in

narcolepsy and sleep medicine and the fundraising and networking expertise of Professor Allouche Aknin will prove invaluable as we continue

to evolve as a business and continue our mission to develop better therapies to safeguard and empower the brain throughout all stages

Generating pre-approval, non-dilutive revenues

In November 2022, NLS launched a paid for Named

Patient Program (NPP) for patients suffering from idiopathic hypersomnia (IH). Although the initial agreement was with Caligor Coghlan

Pharma Services, we have terminated this agreement and plan to enter into a partnership with Durbin Global, a full-service, Expanded Access

partner to pharmaceutical and biotech companies. The program will provide access to Mazindol ER for people living with narcolepsy who

currently have no approved treatment options in the EU, UK and Rest-of-World (excluding the U.S. and Canada).

As we close the books on 2023, I want to remind

you of what NLS stands for and the critical elements that drive us forward each day. Our vision is to awaken a brighter future for patients

by overcoming rare and complex CNS diseases and our mission is to develop better therapies to safeguard and empower the brain throughout

all stages of life. Looking forward, we will continue to be motivated by our shared purpose of "connecting brains" as we work

together to create a culture that inspires and motivates our team members to do what they do best. Our passionate team members make every

effort to remain flexible and steadfast, always putting patients first.

In closing, I want to offer my sincerest gratitude

to each of our incredibly talented people around the world for their hard work and commitment to delivering value every day. And to our

shareholders, investors and partners, your ongoing trust and support help us make NLS the best it can be, every day. Thank you for the

trust you place in and shared commitment to NLS Pharmaceutics.

I wish all our stakeholders a happy and healthy

year-end as we look forward to a prosperous and productive 2024!

Chief Executive Officer

About NLS Pharmaceutics Ltd.

NLS Pharmaceutics Ltd. (Nasdaq: NLSP) is

a global development-stage biopharmaceutical company, working with a network of world-class partners and internationally recognized

scientists, focused on the discovery and development of innovative therapies for patients with rare and complex central nervous system,

or CNS, disorders, who have unmet medical needs. Headquartered in Switzerland and founded in 2015, NLS is led by an experienced management

team with a track record of developing and commercializing product candidates. For more information, please visit www.nlspharma.com.

Safe Harbor Statement

This letter 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 Mazindol ER's

potential, the expected progress of its pipeline and opportunities and timing of clinical trials, its ability to obtain fast track designation,

its ability to secure suitable capital, the potential benefits of

NLS' and Aexon Labs' products, development plans and timing of studies, and the timing and the expected outcome of the option agreement,