NLS Pharmaceutics Announces Positive Mazindol Study Results in Narcoleptic Rat Model

NLS Pharmaceutics Ltd., a Swiss clinical-stage biopharmaceutical firm listed on NASDAQ (NLSP, NLSPW), has unveiled encouraging results from its preclinical study KO-874 at the American Society of Clinical Psychopharmacology (ASCP) conference in Miami. This research primarily examined the neuroprotective effects of mazindol on nocturnal activity, utilizing a rat model to simulate narcoleptic-like symptoms induced by orexin-B-saporin (OX-B-SAP) lesions in the lateral hypothalamus.

Eric Konofal, MD, PhD, Chief Scientific Officer of NLS Pharmaceutics, emphasized the company's dedication to advancing their therapeutic pipeline, highlighting mazindol's potential to transform treatment for patients suffering from sleep and wakefulness disorders, particularly narcolepsy.

The study demonstrated that administering mazindol at a dose of 3 mg/kg effectively mitigated the reduction in circadian activity typically induced by OX-B-SAP lesions. By the 21st day, mazindol not only restored but surpassed normal activity levels during the dark phase, indicating a strong protective effect against orexin cell loss. In contrast, a lower dose of 1 mg/kg showed no therapeutic benefits and potentially worsened activity reduction between days 5 and 8 post-lesion. The results suggest mazindol might modulate orexin receptors or pathways influenced by the orexin system, although the treatment didn't significantly alter the number of orexin neurons, indicating a complex interaction.

The study involved Sprague-Dawley rats with OX-B-SAP lesions in the lateral hypothalamus to mimic narcoleptic symptoms. Key study parameters included continuous circadian activity monitoring and post-mortem histological analysis to assess orexin neuron loss. The findings revealed that mazindol-treated rats exhibited higher activity levels during the dark phase compared to those treated with a vehicle, corroborating mazindol's neuroprotective efficacy.

These promising results from study KO-874 support further clinical development of mazindol as a potential therapeutic for narcolepsy and other disorders involving orexin system disruption. NLS Pharmaceutics remains committed to advancing this promising compound through clinical trials to address significant unmet needs in sleep and wakefulness disorders.

NLS Pharmaceutics Ltd. is led by an experienced management team committed to developing and repurposing product candidates for rare and complex central nervous system disorders. Their lead product candidate, Quilience®, an extended-release formulation of Mazindol (Mazindol ER), is being developed for treating narcolepsy and potentially other sleep-wake disorders like idiopathic hypersomnia (IH), for which they recently obtained Orphan Disease Designation (ODD) from the European Medicines Agency (EMA). Mazindol, a triple monoamine reuptake inhibitor and partial Orexin-2 Receptor agonist, has been used in compassionate use programs for treating narcolepsy. A Phase 2a multi-center U.S. clinical trial evaluating Quilience® in adult narcolepsy patients met its primary endpoint with high statistical significance, demonstrating a favorable safety and tolerability profile. Additionally, NLS completed a Phase 2 study in the U.S. evaluating Nolazol® (Mazindol Controlled-Release) in adult ADHD patients, meeting all primary and secondary endpoints, with Nolazol® being well-tolerated. Quilience® has received Orphan Drug Designations in both the U.S. and Europe for narcolepsy treatment. Notably, up to one-third of narcoleptic patients are also diagnosed with ADHD.

Overall, NLS Pharmaceutics' announcement highlights the potential of mazindol in redefining treatment paradigms for sleep and wakefulness disorders, reaffirming the company's commitment to addressing significant unmet medical needs through ongoing clinical trials and development efforts.