Benzinga | Nov 30, 2021 04:48PM EST

NLS Pharmaceutics Announces Preclinical Results From Study Of NLS-4 For Circadian Rhythm Dysregulation And Chronic Fatigue Syndrome In Long-Covid Model

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, announces final results from a preclinical study for NLS-4 (Lauflumide), the Company's next-generation wake-promoting drug candidate. Based on the results, the Company believes that NLS-4 offers promise to become a foundational treatment for the chronic fatigue associated with the symptoms of Long-Covid (also known as "Chronic Fatigue caused by Covid-19 infection").

The aim of the study was to examine the effectiveness of NLS-4 in comparison with modafinil, a widely-used first-line wake-promoting treatment. NLS-4 is designed to be a more potent next-generation modafinil that does not induce the hepatic toxicity associated with long-term modafinil use. In the study's Long-Covid animal model, NLS-4 improved circadian rhythm dysregulation and chronic fatigue syndrome (CFS) in subject animals. Based on the results, the Company believes that NLS-4 should improve recovery from CFS in humans at a dose that is four times lower than that used for modafinil.

NLS had previously communicated that Sprague-Dawley rats subjected to a fatigue procedure for 7 days that induced CFS recovered with NLS-4 treatment, and were able to exhibit typical nighttime activity when rats are normally active. The final results confirm that NLS-4 treatment produced an increase in locomotor activity which may reduce the impairment of circadian rhythm at doses four times lower than modafinil.In the study, nighttime activity in NLS-4 treated rats was observed to be comparable to rats that did not undergo the fatigue procedure, the study's control group.

An increasing proportion of Covid-19 patients are suffering from prolonged symptoms that are typically found in patients diagnosed with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). However, the effects of current treatments proposed for this condition have been inconclusive.

"We believe that these final results from this cutting-edge preclinical study confirm that NLS-4 (Lauflumide) expressed motor-stimulating effects, which are superior to the widely prescribed fatigue treatment, modafinil at all doses. The ability of Lauflumide to enable rats that have undergone the fatigue procedure to recover is a strong indicator of the drug's potential to treat diseases in which CFS is a key symptom," said Eric Konofal, MD, Chief Scientific Officer of NLS Pharmaceutics. "The fatigue procedure induced a decrease in body weight, and therefore we also examined the weight growth curve in rats treated by NLS-4 at its lowest doses. Importantly, weight loss was not modified by NLS-4 (16 mg/kg). Stimulants commonly prescribed off-label to treat fatigue symptoms decrease appetite and weight loss is a common side effect, whereas Lauflumide at low doses did not cause these issues."

"Excessive fatigue, daytime sleepiness, deficit of alertness and disturbed sleep are some of the main symptoms found in patients who have contracted Covid-19, and today, there is no approved therapeutic agent for the improvement of the CFS associated with Long-Covid," said Alex Zwyer, Chief Executive Officer of NLS Pharmaceutics. "We look forward to advancing the development of NLS-4, as the unmet medical need for improved fatigue treatments is growing with more patients surviving infection with Covid-19 and its variants."

About NLS-4 (Lauflumide) and its pre-clinical safety profile

NLS-4 (Lauflumide) is a next-generation selective dopamine reuptake inhibitor. Contrary to modafinil treatment, which can cause hepatic enzyme induction with repeated dosing, NLS-4 did not induce cytochrome P450 (CYP) enzymes, including CYP3A4/5 when tested in human cell cultures.NLS believes that NLS-4 is the only wake-promoting compound without any rebound hypersomnia. This "hypnolytic effect" of NLS-4 is thought to be due to the compound's ability to prevent increased sleep need following sleep loss as supported by the final pre-clinical results.With the promising results from the cutting-edge preclinical fatigue study in animals, and the apparent absence of CYP450 enzyme induction, NLS-4 appears to have a superior profile compared to the widely used drug modafinil, and potentially represents an important milestone in the development of this next generation wake-promoting agent.