NLS Pharmaceutics Announces New Study Data Confirming Mazindol's Unique Orexin Pathway Activation for Treating Narcolepsy

STANS, Switzerland, May 18, 2021 /PRNewswire/ -- NLS Pharmaceutics Ltd. NLSP NLSPW))) ("NLS" or the "Company"), a Swiss clinical-stage pharmaceutical company focused on the discovery and development of innovative therapies for patients with rare and complex central nervous system disorders, announces new study data which support the mechanism of action for mazindol, the active compound in the Company's lead product candidate to treat narcolepsy, Quilience®. Narcolepsy is caused by a deficiency in orexin, a neuropeptide that regulates the sleep-wake cycle. The new data confirm mazindol's Orexin-2 receptor (OX2R) agonist activity.

In the pre-clinical study conducted by the Department of Biomedical Sciences at the University of Lausanne and sponsored by NLS, mice that were genetically modified not to express OX2R (Knock-Out mice) and Wild-Type mice (normal mice) were investigated for psychostimulant effects when mazindol was administered. The study demonstrated that Knock Out mice were 70% less sensitive to mazindol compared to normal mice, confirming mazindol's potent activity as an OX2R agonist.

Ongoing studies sponsored by the Company are intended to further confirm and extend this finding to the wake-promoting and anti-cataplexy effects of mazindol, which have been observed in human studies and in clinical practice when the drug was prescribed to treat narcolepsy in compassionate use programs. NLS believes that the new data also support prior in-vitro data from studies conducted by the Company demonstrating the partial binding affinity of mazindol to OX2R, which NLS believes is a key pathway that mediates mazindol's stimulant-like effects. Mazindol is a scheduled IV controlled substance unrelated to amphetamine salts, which are highly regulated and have restricted use.

"We believe these study results confirm that mazindol has a surprisingly unique mode of action, not only as a reuptake blocker of monoamines in the central nervous system like other stimulants, but also having psychostimulant effects through the activation of OX2R," said Mehdi Tafti, Ph.D., Professor at the University of Lausanne, Department of Biomedical Sciences. "Given that narcolepsy is caused by orexin deficiency, this finding is important as mazindol has the potential to become the first-available treatment targeting Orexin-2 receptors, and the first evidence-based medicine to address this chronic sleep disorder."

"The results of this Knock Out mouse study demonstrate mazindol's potent binding activity to OX2R, which we believe will translate into clinically meaningful results in humans suffering from the core symptoms of narcolepsy – excessive daytime sleepiness and cataplexy attacks," said Eric Konofal, M.D., Ph.D., Co-founder and interim Chief Scientific Officer of NLS. "Clinical data from real-world mazindol use, as well as trial results from other orexin-activating compounds validate the utility of orexin receptor stimulation and the potential benefits to both narcolepsy Type 1 and narcolepsy Type 2 patients. We believe that Quilience® will provide a differentiated solution in this treatment category given mazindol's dual mechanism of action, namely orexin pathway activation and pan-monoaminergic reuptake inhibition in the brain. Overall, we believe that the unique pharmacological profile of mazindol will offer synergies that could translate into improved efficacy compared to current treatments, as well as those in development that purely target OX2R. 

"We are dedicated to the development of Quilience®, our proprietary controlled-release formulation of mazindol, which we believe has the potential to provide a superior solution in the treatment of narcolepsy by addressing the disorder at its root cause," said Alexander Zwyer, Chief Executive Officer of NLS. "Mazindol has been used over many years to treat refractory narcoleptic patients off-label, with evidence of favorable efficacy and safety. We believe that these new preclinical results further support the rationale for our clinical program intended to bring mazindol back to the market in an optimized formulation that can benefit patients diagnosed with narcolepsy and potentially other sleep-wake disorders."

About NLS Pharmaceutics Ltd.

NLS Pharmaceutics Ltd. is a Swiss-based clinical-stage biopharmaceutical company led by an experienced management team with a track record of developing and repurposing product candidates to treat rare and complex central nervous system disorders. The Company's lead product candidate, Quilience® is a proprietary controlled release formulation of mazindol (mazindol CR), and is being developed for the treatment of narcolepsy. Mazindol is a triple monoamine reuptake inhibitor and partial Orexin-2 receptor agonist, which was used for many years to treat patients diagnosed with narcolepsy in compassionate use programs. NLS completed a Phase 2 study in the U.S. evaluating mazindol CR in adult subjects with ADHD. The study met all primary and secondary endpoints and was well-tolerated. Quilience® has received Orphan Drug Designations both in the U.S. and in Europe for the treatment of narcolepsy.

Safe Harbor Statement

This press release contains express or implied forward-looking statements pursuant to U.S. Federal securities laws. For example, NLS is using forward-looking statements when it discusses the intent of ongoing and future studies, its belief that the partial binding affinity of mazindol to OX2R is a key pathway that mediates mazindol's psychostimulant effects, the belief that mazindol has a unique mode of action and that mazindol has the potential to become the first-available treatment targeting Orexin-2 receptors and the first evidence-based medicine to address this chronic sleep disorder, that Quilience® may potentially provide a superior solution in the treatment of narcolepsy by addressing its root cause, that the results from the announced preclinical study support results of prior NLS studies, and that the results from the announced preclinical study support the rationale for bringing mazindol back to the market. 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's products may not be approved by regulatory agencies, NLS's 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's process; NLS's 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's patents may not be sufficient; NLS's products may harm recipients; changes in legislation may adversely impact NLS; inability to timely develop and introduce new technologies, products and applications; 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's prospectus dated January 28, 2021 filed with the SEC, which is available on the SEC's website, www.sec.gov.

Corporate Contact:
Alex Zwyer, CEO: +41 41 618 80 00 

Investor Relations Contact
David Moskowitz: +1 202-280-0888 

www.nlspharma.com

SOURCE NLS Pharmaceutics Ltd.