Quilience (mazindol CR) / NLS Pharma - LARVOL DELTA

Sex-specific effects of appetite suppressants on stereotypy in rats (Neuroscience 2025) - "Network analysis and Markov transition matrices revealed distinct behavioral profiles associated with head-weaving, which emerged as the dominant attractor state, suggesting potential mechanistic differences among these drugs. Collectively, this study provides a valuable database characterizing the behavioral side effects of appetite suppressants."

Preclinical • CNS Disorders • Movement Disorders

AMAZE: A Eight-Week Study of NLS-2 (Mazindol Extended Release) in Participants With Narcolepsy Type 1 (clinicaltrials.gov) - P3 | N=48 | Not yet recruiting | Sponsor: NLS Pharmaceutics | Trial completion date: Feb 2025 ➔ Jul 2025 | Initiation date: Jan 2024 ➔ Jul 2024 | Trial primary completion date: Jan 2025 ➔ Jul 2025

Trial completion date • Trial initiation date • Trial primary completion date • Cataplexy • Narcolepsy • Sleep Disorder

Neuroprotective Effect of Mazindol on Nocturnal Activity in an Orexin-B-Saporin-Induced Narcoleptic-Like Model in Sprague-Dawley Rats (ASCP 2024) - "Learning Objectives Demonstrate an understanding of the OX-B-SAP lesioned rat and its use in drug development in narcolepsy research. Identify and explain the role of orexin neurons and their functions, particularly during the dark phase in rats."

Preclinical • CNS Disorders • Narcolepsy • Sleep Disorder

AMAZE: A Eight-Week Study of NLS-2 (Mazindol Extended Release) in Participants With Narcolepsy Type 1 (clinicaltrials.gov) - P3 | N=48 | Not yet recruiting | Sponsor: NLS Pharmaceutics | Trial completion date: Aug 2024 ➔ Feb 2025 | Initiation date: Jul 2023 ➔ Jan 2024 | Trial primary completion date: Jul 2024 ➔ Jan 2025

Trial completion date • Trial initiation date • Trial primary completion date • Cataplexy • Narcolepsy • Sleep Disorder

Altered Levels Of Dopamine Transporter In The Frontal Pole And The Striatum In Mood Disorders: A Postmortem Study (CINP 2023) - "Our data suggest that changes in levels of DAT may be selectively affecting dopamine homeostasis in BA 10 in patients with MDD. Given the critical role of cortical dopamine and the frontal pole in the maintenance of human cognitive ability we hypothesise that higher levels of DAT in MDD could be involved in the cognitive deficits experience by patients with this disorder."

Bipolar Disorder • CNS Disorders • Cognitive Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

AMAZE: A Eight-Week Study of NLS-2 (Mazindol Extended Release) in Participants With Narcolepsy Type 1 (clinicaltrials.gov) - P3 | N=48 | Not yet recruiting | Sponsor: NLS Pharmaceutics

New P3 trial • Cataplexy • Narcolepsy • Sleep Disorder

Mazindol ER: Pioneering the Combination of OX2R and SNDRI in the Treatment of Narcolepsy (SLEEP 2023) - "Supported By Dragonfly Agency, supported by NLS Pharmaceuticals"

CNS Disorders • Narcolepsy • Sleep Disorder

A four-week randomized, double-blind, placebo-controlled, phase 2 study of mazindol ER in the treatment of narcolepsy (SLEEP 2023) - P2 | "NLS-2 was generally safe and well-tolerated with no severe or serious adverse events or discontinuations due to adverse events. Conclusion In subjects with narcolepsy, NLS-2 significantly improved EDS and the number of cataplexy attacks compared with placebo."

Clinical • P2 data • Cataplexy • CNS Disorders • Excessive Daytime Sleepiness • Narcolepsy • Sleep Disorder

Long-term efficacy on cataplexy attacks and excessive daytime sleepiness in open-label extension study (NLS-1022) of mazindol ER (SLEEP 2023) - P2 | "Conclusion Mazindol ER is a convenient, safe, well-tolerated and effective treatment for narcolepsy. Its anticataleptic and wake-promoting effects indicate that it may be a new therapeutic option for patients with NT1 or NT2 similar or better than various combinations treatments currently available."

Clinical • Cataplexy • CNS Disorders • Excessive Daytime Sleepiness • Narcolepsy • Sleep Disorder

Clinician and Patient Global Impression in a Phase 2 Study of Mazindol (NLS-1021) in Adults with Narcolepsy Type 1 and Type 2 (SLEEP 2023) - P2 | "Patients were treated with mazindol ER (NLS-2) at once-daily 2 mg for one week and once-daily 3 mg thereafter or matching placebo (PBO) on a 1:1 ratio...Conclusion Mazindol ER resulted in significant improvements of cataplexy severity and sleepiness in both conditions as rated by both clinicians and participants. These secondary outcome results support the efficacy of mazindol ER on cataplexy attacks, in NT1 participants, and on sleepiness, in NT1 as well as in NT2 participants."

Clinical • P2 data • Cataplexy • CNS Disorders • Excessive Daytime Sleepiness • Narcolepsy • Sleep Disorder

Functional Outcomes of Sleep Questionnaire in a phase 2 study of mazindol ER in narcolepsy (SLEEP 2023) - P2 | "Patients were treated with mazindol ER (NLS-2) at once-daily 2 mg for one week and once-daily 3 mg thereafter or matching placebo (PBO) on a 1:1 ratio...The most frequently reported TEAEs (>5%) were dry mouth, nausea, decreased appetite and tachycardia. Conclusion Mazindol ER resulted in significant improvements of functional outcome measure FOSQ-10 These secondary outcome results support the efficacy of mazindol ER on cataplexy attacks, in NT1 patients, and on sleepiness, in NT1 as well as in NT2 patients."

P2 data • Cataplexy • CNS Disorders • Narcolepsy • Sleep Disorder

An Open Label Study of NLS-2 (Mazindol Extended Release) in Subjects With Narcolepsy (clinicaltrials.gov) - P2 | N=52 | Completed | Sponsor: NLS Pharmaceutics | Active, not recruiting ➔ Completed

Trial completion • Cataplexy • Narcolepsy • Sleep Disorder

An Open Label Study of NLS-2 (Mazindol Extended Release) in Subjects With Narcolepsy (clinicaltrials.gov) - P2 | N=52 | Active, not recruiting | Sponsor: NLS Pharmaceutics | Enrolling by invitation ➔ Active, not recruiting

Enrollment closed • Cataplexy • Narcolepsy • Sleep Disorder

Four-week Study of the Safety and Efficacy of NLS-2 (Mazindol Extended Release) in the Treatment of Narcolepsy (clinicaltrials.gov) - P2 | N=67 | Completed | Sponsor: NLS Pharmaceutics | Active, not recruiting ➔ Completed

Trial completion • Cataplexy • Excessive Daytime Sleepiness • Narcolepsy • Sleep Disorder

Four-week Study of the Safety and Efficacy of NLS-2 (Mazindol Extended Release) in the Treatment of Narcolepsy (clinicaltrials.gov) - P2 | N=67 | Active, not recruiting | Sponsor: NLS Pharmaceutics | Recruiting ➔ Active, not recruiting

Enrollment closed • Cataplexy • Excessive Daytime Sleepiness • Narcolepsy • Sleep Disorder

Four-week Study of the Safety and Efficacy of NLS-2 (Mazindol Extended Release) in the Treatment of Narcolepsy (clinicaltrials.gov) - P2; N=60; Recruiting; Sponsor: NLS Pharmaceutics; Enrolling by invitation ➔ Recruiting

Clinical • Enrollment status • Cataplexy • Excessive Daytime Sleepiness • Narcolepsy • Sleep Disorder

NLS Pharmaceutics CEO Issues Letter to Shareholders (Yahoo Finance) - "...We reported positive pre-clinical data for NLS-4...We intend to advance this compound into clinical development ourselves or with a partner in 2022. As we advance the ongoing Phase 2a trial comparing Quilience to placebo to treat the core symptoms of narcolepsy, we have offered patients the option to roll into a 6-month open label extension (OLE) study, enabling trial participants to remain on Quilience free of charge for an additional half year....We now anticipate reporting interim top-line results for POLARIS in the first quarter of 2022....Activities and events that we anticipate delivering though the end of this year and in 2022 include: final granting of our U.S. patent protecting Quilience's novel once-daily formulation; an investigator presentation at the Wake Up Narcolepsy patient advocacy webinar in November highlighting Quilience and our ongoing Phase 2a clinical program."

New P1 trial • P2a data • Patent • Preclinical • Cataplexy • CNS Disorders • Narcolepsy • Sleep Disorder

"Safety signal scuppers two phase 2 trials of @Takedapharma's orexin agonist TAK-994 for #narcolepsy, handing a possible advantage to @NLSPharma rival Quilience #pharma https://t.co/oIxEM2kwZu" (@pharmaphorum)

Clinical • Narcolepsy • Sleep Disorder

An Open Label Study of NLS-2 (Mazindol Extended Release) in Subjects With Narcolepsy (clinicaltrials.gov) - P2; N=60; Not yet recruiting; Sponsor: NLS Pharmaceutics

New P2 trial • Cataplexy • Narcolepsy • Sleep Disorder

NLS Initiates Phase 2 Trial for Quilience in Narcolepsy and Announces First Patient Enrolled (Yahoo Finance) - "NLS Pharmaceutics Ltd...announces the initiation of its Phase 2 clinical trial evaluating Quilience® (mazindol extended release or 'ER') as a once-daily monotherapy for the treatment of excessive daytime sleepiness (EDS) and cataplexy, the primary symptoms of narcolepsy. The Company has begun enrolling patients and plans to conduct the trial in approximately 30 specialized centers across the U.S. and Europe....'we remain focused on delivering top line results by year-end to demonstrate the potential benefits and safety profile of Quilience in the treatment of narcolepsy...'"

P2 data • Trial status • Cataplexy • CNS Disorders • Excessive Daytime Sleepiness • Narcolepsy • Sleep Disorder

Four-week Study of the Safety and Efficacy of NLS-2 (Mazindol Extended Release) in the Treatment of Narcolepsy (clinicaltrials.gov) - P2; N=60; Recruiting; Sponsor: NLS Pharmaceutics; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Cataplexy • Excessive Daytime Sleepiness • Narcolepsy • Sleep Disorder

NLS Pharmaceutics Shares Increase Over 30% Intraday: Why It Happened (Pulse) - "The shares of NLS Pharmaceutics Ltd. (NASDAQ: NLSP)...increased by over 30% intraday. Investors are responding positively to the company announcing that it has received a Notice of Allowance from the U.S. Patent and Trademark Office (USPTO) for patent application No. 16/083,131. When the patent issues, it will cover oral formulations containing immediate-release and sustained-release layers of mazindol and their use in the treatment of attention deficit disorders (ADD or ADHD), related deficit of alertness or decline in vigilance, or excessive daytime sleepiness (e.g., narcolepsy, idiopathic hypersomnia)."

Patent • Stock price • CNS Disorders • Excessive Daytime Sleepiness in Narcolepsy • Narcolepsy • Sleep Disorder

NLS Pharmaceutics Announces Notice of Allowance for U.S. Patent Application Covering its Proprietary Mazindol Formulation (Yahoo Finance) - "NLS Pharmaceutics Ltd...announces that it has received a Notice of Allowance from the U.S. Patent and Trademark Office ('USPTO') for patent application No. 16/083,131. When the patent issues, it will cover oral formulations containing immediate-release and sustained-release layers of mazindol and their use in the treatment of attention deficit disorders (ADD or ADHD), related deficit of alertness or decline in vigilance, or excessive daytime sleepiness (e.g., narcolepsy, idiopathic hypersomnia)....The patent, which is expected to be issued in the fourth quarter of 2021, will have a term that expires no earlier than March 2037....NLS would promptly list the patent in the U.S. Food and Drug Administration's (FDA) Approved Drug Products with Therapeutic Equivalence Evaluations, or Orange Book if it receives market approval."

Patent • Cataplexy • CNS Disorders • Narcolepsy • Sleep Disorder

NLS Pharmaceutics Announces FDA Acceptance of IND Application to Initiate Clinical Trials with Quilience (mazindol ER) to Treat Narcolepsy (Yahoo Finance) - "NLS Pharmaceutics...announces that the U.S. Food and Drug Administration (FDA) has accepted its Investigational New Drug application (IND) for Quilience® (mazindol extended release, or mazindol ER)...for the treatment of narcolepsy. The open IND enables NLS to initiate its Phase 2a clinical trial to assess the safety and efficacy of Quilience® in patients diagnosed with narcolepsy....The proposed multi-center study, to be conducted in both the U.S. and Europe, is expected to enroll 60 patients and commence in August 2021. The primary endpoint is the change from baseline in excessive daytime sleepiness (EDS) as measured by the Epworth Sleepiness Scale (ESS), and a key secondary endpoint is the change from baseline in mean weekly number of cataplexy attacks in the anticipated subset of patients with cataplexy."

IND • New P2a trial • Cataplexy • CNS Disorders • Narcolepsy • Sleep Disorder

Four-week Study of the Safety and Efficacy of NLS-2 (Mazindol Controlled Release) in the Treatment of Narcolepsy (clinicaltrials.gov) - P2; N=60; Not yet recruiting; Sponsor: NLS Pharmaceutics

Clinical • New P2 trial • Cataplexy • Excessive Daytime Sleepiness • Narcolepsy • Sleep Disorder