NLS Pharmaceutics to Present New Data on the Dual Efficacy of Mazindol ER in Fentanyl Reward and Withdrawal at the 2025 ASCP Annual Meeting

ZURICH, May 21, 2025 /PRNewswire/ -- NLS Pharmaceutics Ltd. (NASDAQ: NLSP), a Swiss clinical-stage biopharmaceutical company focused on central nervous system ("CNS") disorders, announces that it will present new preclinical data on Mazindol ER at the 2025 Annual Meeting of the American Society of Clinical Psychopharmacology ("ASCP"). ASCP Annual Meeting will be held at the Fairmont Scottsdale Princess in Scottsdale, Arizona from May 27, 2025, to May 30, 2025. NLS intends to present its poster titled, 'Evaluating the Effects of Mazindol on Fentanyl Reward and Dependence in C57BL/6J Mice and Sprague-Dawley Rats (Study KO-943),' during the poster session on May 29, 2025, from 11:15 AM to 1:00 PM.

The preclinical study to be featured in the poster was conducted by Key-Obs SAS in collaboration with NLS and other European academic institutions. The study results demonstrate that Mazindol significantly reduced both the rewarding effects of fentanyl and the severity of its withdrawal symptoms in validated rodent models.

Highlights from Study KO-943:

• Experiment 1 (Reward/CPP Model): In C57BL/6J mice, Mazindol at 0.5 mg/kg significantly reduced fentanyl-induced conditioned place preference ("CPP"), effectively neutralizing the behavioral reward effects typically observed with fentanyl exposure.
• Experiment 2 (Withdrawal Model): In Sprague-Dawley rats, Mazindol administered at 0.5 and 1.0 mg/kg dose-dependently reduced fentanyl withdrawal symptoms, including agitation, salivation, and motor disturbances, as measured by the Gellert-Holtzman scale.

Expert Commentary

"The study results show that Mazindol produced robust effects on both reward and withdrawal symptoms, demonstrating its potential as a non-opioid therapeutic candidate option for fentanyl dependence," said Dr. Jean-Charles Bizot, Director of Research at Key-Obs SAS and lead investigator of Study KO-943. "The data support further exploration in clinical models, particularly given the multi-receptor activity of Mazindol."

"These data suggest the potential of a multiple-target profile for Mazindol to address opioid addiction through a novel mechanism of action.  By targeting partial mu-opioid as receptor agonist, strong 5-HT1A receptor agonist activity, and orexin-2 receptor modulation, Mazindol may offer a unique, multi-modal strategy to reduce opioid reward and withdrawal symptoms, showing its potential as a non-opioid therapeutic. These findings are supported by results from both reward and withdrawal animal models, including the CPP paradigm in C57BL/6J mice and naloxone-precipitated withdrawal in Sprague-Dawley rats. Clinical trials, including the planned NLS-6002 study, are needed to validate these results in humans," said Dr. Eric Konofal, MD, PhD, Chief Scientific Officer of NLS Pharmaceutics.

Broader Implications for ADHD and CNS Disorders

While standard stimulant and non-stimulant medications approved for ADHD have shown no significant efficacy in addressing opioid withdrawal or reward, Mazindol's ability to reduce both in fentanyl-exposed animals suggests it may offer advantages over conventional treatments. This aligns with clinical observations that differentiate the pharmacodynamic profile of Mazindol from traditional monoaminergic agents, as discussed in comparative studies such as Wigal et al., CNS Drugs (2018).

About ASCP

The ASCP Annual Meeting is one of the world's premier scientific events for advancing neuropsychopharmacology and psychiatry. It brings together leading clinicians, researchers, and innovators to present and discuss the latest advances in CNS therapeutics.

About NLS Pharmaceutics Ltd.

NLS Pharmaceutics Ltd. is a Swiss-based clinical-stage biopharmaceutical company developing innovative therapies for rare and complex CNS disorders. The company's pipeline includes drug candidates for ADHD, narcolepsy, hypersomnia, and substance use disorders, with a focus on repurposed and reformulated compounds.

For more information, visit www.nlspharma.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 potential of Mazindol ER for the treatment of fentanyl dependence and other possible conditions. 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; changes to the results of trials and 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; changes to the Study KO-943; 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, 2024 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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SOURCE NLS Pharmaceutics Ltd.