In a letter to shareholders, the CEO of Swiss clinical-stage biopharmaceutical company NLS Pharmaceutics Ltd recapped the company’s progress and pitfalls for 2023.

NLS Pharmaceutics’ objectives for 2023, according to CEO Alex Zwyer, MBA, were:

  • Continuing to build an organization dedicated to rare and complex central nervous system (CNS) disorders
  • Solidifying the opportunity for lead product Mazindol ER’s success through a rigorous phase 3 program
  • Realizing Mazindol ER’s full potential across a variety of rare sleep disorders
  • Progressing pipeline of innovative products to meet the unmet needs of patients and transforming the lives of patients with rare diseases.

“Despite many challenges, we have delivered on many of these as well as other accomplishments,” Zwyer details in his letter.

NLS Pharmaceutics 2023 Clinical Successes

In 2022, NLS Pharmaceutics reported on positive full results from the phase 2 clinical trial (NLS-1021) and open-label extension (NLS-1022) evaluating its 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. The results were presented at SLEEP 2023 in Indianapolis 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.

In July 2023, NLS Pharmaceutics announced that the phase 3 clinical trial (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 Pharmaceutics has retained a contract research organization and enrolled sites for the phase 3 studies. Once suitable capital has been secured, NLS expects the phase 3 program to commence as the sites are ready to begin enrolling patients.

Ongoing Business Development

Agreement with Aexon Labs

In early December, it was announced that NLS Pharmaceutics had entered into an exclusive worldwide option agreement with Aexon Labs, Inc, a privately held US company, 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 with potential applications in the treatment of narcolepsy and idiopathic hypersomnia, as well as neurodegenerative 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,” Zwyer says in the letter. Aexon Labs has plans to initiate proof-of-concept preclinical development in 2024.

“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 neurodegenerative disorders,” Zwyer adds. “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.”

Exploring Strategic Alternatives

In addition, NLS Pharmaceutics 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 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,” Zwyer says. “Several strategic partnership discussions are currently underway and in advanced stages of negotiations. As always, we continue to approach the sleep medicine market from a holistic perspective.” 

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