2018 Biotechnology Awards

26 GHP / Biotechnology Awards 2018 , Established in 2015, NLS is a Swiss based clinical-stage biotechnology company focused on developing novel and innovative treatments for Attention- deficit/hyperactivity disorder (ADHD), providing superior treatment alternatives to existing treatments. ADHD is one of the most prevalent psychiatric disorders in children and adults worldwide. First-line pharmacological management is with psychostimulants, such as methylphenidate and amphetamine, which are Schedule II controlled substances (C2, per the US Drug Enforcement Agency [DEA]). While C2 stimulants are highly effective for ADHD, stimulants are misused recreationally with both diversion and abuse being common problems. Furthermore, not all individuals respond optimally to or tolerate C2 stimulants because of adverse events. Non-stimulants (e.g., atomoxetine and alpha-2 agonists such as long-acting clonidine and guanfacine) are Food and Drug Administration (FDA)-approved for ADHD, but efficacy, overall, is not as robust as with C2 stimulants. Moreover, the tolerability profile is not necessarily superior to stimulants. The “holy grail” in ADHD is yet to be developed: a therapeutic agent that is effective as a stimulant and at the same time as safe and well-tolerated as a lower scheduled product. BI180012 Best Quality of life Improvement Pharmaceuticals Company - Central Europe IsNLS-1 PharmaAG (NLS) developing a game-changing treatment in theADHDspace?We explore thefirm’s latest development tofindoutmore. Mazindol CR (MoA: dual pan- monoamine reuptake inhibitor / Orexin receptor type 2 partial agonist) is a novel, proprietary, controlled-release formulation of a medication that was initially developed for the short-term treatment of obesity in 1973, and withdrawn from United States (US)/ European markets by 2002 due to commercial reasons (not due to safety or efficacy). When marketed, mazindol immediate release (IR) was a Schedule IV controlled substance (C4, per the US Drug Enforcement Agency [DEA]). A recent phase 2 study provided the first evidence that mazindol CR is efficacious and well tolerated in adults with ADHD. Mazindol CR had a robust effect on ADHD symptoms, with a large placebo-adjusted effect size of 1.09. The magnitude of this effect was comparable to what is typically seen with stimulants, such as methylphenidate CR, lisdexamfetamine, d-amphetamine extended release (XR), and mixed amphetamine salts, and much higher than for atomoxetine. The least square means (LS) mean difference between mazindol CR and placebo on Day 42 was found to be consistent across all sensitivity analyses, establishing that the large effect size was not biased by any of the statistical methods used. In addition, onset of action was rapid; separation from placebo was seen at the first post-treatment data point, after 1 week of treatment. Further, there was a significantly higher proportion of excellent responders and responders on the Clinical Global Impression (CGI-I) (much or very much improved) by Day 14; this finding stands in contradistinction to time to onset of effect for FDA- approved nonstimulant agents (e.g., atomoxetine, guanfacine, and clonidine), which can take up to 4 weeks to achieve efficacy. While the exact mechanism of action (MoA) is under further investigation by NLS-1 scientists, the pharmacologic profile of mazindol suggests that it might be useful for treating ADHD. Mazindol CR is unique from other available medications for ADHD because none of the currently approved pharmacological treatments are considered Selective Norepinephrine Dopamine Reuptake Inhibitors (SNDRI), nor do they promote a regulatory effect on 5-HT1A, 5-HT7, or the hypothalamic orexin system. Orexin fibers are dense in brain regions crucial for wakefulness and arousal particularly the locus coeruleus that contains adrenergic, noradrenergic, histaminergic, and serotonergic neurons. Orexin neuropeptides are known to play important modulatory roles in sleep/wake regulation, motivation, reward, as well as emotional and attentional regulation. Mazindol CR differentiated MoA, promising clinical results to-date and lower expected schedule IV could potentially pave the way for a game- changing treatment for ADHD