σ receptor x DAT

The option agreement grants NLS Pharmaceutics Ltd. the exclusive option to in-license all of Aexon Labs' assets for the potential treatment of narcolepsy and other neuro-degenerative disorders, and all future indications Exclusive option agreement accesses global rights to multiple highly selective Orexin-1 / Orexin-2 receptor agonists, unique compounds designed for specificity, acting multiple pathways involved in the pathophysiology of narcolepsy and other central disorders of hypersomnolence Additional targets include Cathepsin-H inhibition, sigma-1 receptor agonist, DAT and NET reuptake inhibition, addressing neurotransmission, neuroprotection and neuroinflammation First patent application filed at the end of 2022 for orexin receptors agonists for treating or preventing neurological diseases and psychiatric disorders including narcolepsy NLS continues to strengthen its neuroscience pipeline in sleep medicine with a unique and holistic approach to central disorders of hypersomnolence and neurodegenerative disorders franchise ZÜRICH, SWITZERLAND / ACCESSWIRE / December 1, 2023 / NLS Pharmaceutics Ltd. (NASDAQ:NLSP)(NASDAQ: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 ("CNS") disorders, today announced that NLS has entered into an exclusive worldwide option agreement with Aexon Labs, Inc., a privately held U.S. company ("Aexon Labs"), under which NLS may acquire global development and commercialization rights to Aexon Labs' Dual Orexin Receptor Agonists platform, new molecular entities, highly selective dual oral orexin-1 and orexin-2 receptor agonists (OX1R and OX2R) with potential applications in the treatment of narcolepsy and idiopathic hypersomnia, as well as neuro-degenerative disorders such as Parkinson's and Alzheimer's disease. This option agreement represents a potentially leading next-generation, first-in-class, oral, dual orexin receptor agonist (AEX-2) that is expected to address high unmet medical needs and has shown promising results in pre-clinical in vitro assays. Aexon Labs has plans to initiate clinical development, including Phase 1 First-in-Human and Phase 1b Proof-of-Concept (POC) studies, as early as 2024. The transaction will be structured as an exclusive worldwide license for the development and commercialization by NLS of the Aexon Labs' compounds and their derivatives. Under the terms of the option agreement, NLS must exercise its option by no later than March 31, 2024. NLS will pay Aexon Labs an upfront payment of $30,000 for the option exclusivity, and $170,000 upon execution of the definitive agreement to exercise the option. In addition, Aexon Labs will receive 15% of all proceeds earned by NLS in any future sub-licensing agreements which include upfront payments, regulatory milestones, commercial milestones and royalties earned during the first three years of commercialization in the U.S. and in the EU. Royalties will be payable, on a country-by-country basis, from the date of first commercial sale of a product in a given country until the date of patent expiry or the entry of a generic version of the product in such country. NLS will be the sole party responsible for the design and execution of the research and development plan, for the conduct and management of the preclinical as well as clinical studies, and for the interactions with the U.S. Food and Drug Administration and/or any other regulatory agency. NLS will pay all costs associated with executing and completing those studies, as well as those associated with the preparation and submission of a new drug application. NLS will pay for all studies in all indications and regulatory filings in the U.S. as well as outside of the U.S. Eric Konofal, MD, PhD, who works under a part-time consulting agreement for NLS as its Chief Scientific Officer, is the president and founder of Aexon Labs, and owns 59% of Aexon Labs. Alexander Zwyer, Chief Executive Officer of NLS, owns 35% of Aexon Labs. Mr. Zwyer holds no board or executive position at Aexon Labs. Mr. Zwyer said, "I believe the potential acquisition of this novel and unique platform which consists of over 300 compounds, bridges the present to the future treatment of sleep disorders as well as other neuro-degenerative disorders. These new compounds, in addition to our current pipeline, including Mazindol ER for the treatment of narcolepsy, along with NLS-4 focused on idiopathic hypersomnia, long-COVID and chronic fatigue syndrome, and NLS-11, addressing Kleine-Levin Syndrome and neurodegenerative diseases will further complement and strengthen our hypersomnia franchise." Orexin receptor pathways play vital regulatory roles in many physiological processes and studies have shown that orexin receptor pathways are involved in pathological processes of neurological diseases such as narcolepsy, depression, ischemic stroke, drug addiction and Alzheimer's disease. About Narcolepsy Narcolepsy is a life-long sleep disorder caused by the autoimmune-mediated loss of 70,000-90,000 orexin-producing neurons in the hypothalamus, characterized by excessive daytime sleepiness, cataplexy and rapid eye movement sleep abnormalities, and is tightly associated with human leukocyte antigen HLA-DQB1*06:02. Other predisposing factors for narcolepsy are associations with a polymorphism in the T-cell receptor alpha and beta genes, whose products recognize antigens presented by human leukocyte antigens (HLA) molecules, and Cathepsin H (CTSH). About NLS Pharmaceutics Ltd. NLS is a global development-stage biopharmaceutical company, working with a network of world-class partners and internationally recognized scientists, focused on the discovery and development of innovative therapies for patients with rare and complex central nervous system disorders who have unmet medical needs. Headquartered in Switzerland and founded in 2015, NLS is led by an experienced management team with a track record of developing and commercializing product candidates. For more information, please visit . About Aexon Labs, Inc. Aexon Labs is conducting leading edge research on new compounds to address unmet needs in neurodegenerative disorders, defined by the breakdown of neurons over time. Alzheimer's, Parkinson's, Huntington's, Narcolepsy and Amyotrophic Lateral Sclerosis are just a few examples of brain disorders that have no cure. Current treatments do not address the root cause of each disorder and often lack therapeutical effectiveness and safety for these neurological disorders. For more information, please visit . Safe Harbor Statement This press release contains expressed or implied forward-looking statements pursuant to U.S. Federal securities laws. For example, NLS is using forward-looking statements when it discusses the potential benefits of NLS' and Aexon Labs' products, development plans and timing of studies, and the timing and the expected outcome of the option agreement. 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' products may not be approved by regulatory agencies, NLS' 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' process; NLS' 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' patents may not be sufficient; NLS' products may harm recipients; changes in legislation may adversely impact NLS; inability to timely develop and introduce new technologies, products and applications; and 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' annual report on Form 20-F for the year ended December 31, 2022 filed with the Securities and Exchange Commission (SEC), which is available on the SEC's website, and in subsequent filings made by NLS with the SEC. For additional information: Marianne Lambertson (investors & media) NLS Pharmaceutics Ltd. +1 239.682.8500 ml@nls-pharma.com SOURCE: NLS Pharmaceutics AG View source version on accesswire.com:

The agency is asking for comments on the draft guidelines within the next 60 days. The FDA has never had the chance to approve a stimulant use disorder treatment and so the agency has laid out its current thinking on clinical trial design, population selection and clinical endpoint selection, all in an effort to spur new interest in the space.  An unpublished draft guidance, “Stimulant Use Disorders: Developing Drugs for Treatment,” will include recommendations for clinical trials designed specifically to assess treatments for stimulant use disorders, excluding symptoms associated with caffeine or nicotine use. The guidance tackles challenges unique to the space, such as determining the appropriate populations for trials and choosing proper clinical endpoints. The FDA document expands beyond basic considerations of the drug development process, delving into approaches that have proved unsuccessful before and ways to make clinical trial design more patient-centric.  “Currently there is no FDA-approved medication for stimulant use disorder,” Marta Sokolowska, Ph.D., deputy center director for substance use and behavioral health in FDA’s Center for Drug Evaluation and Research, said in an Oct. 4 release. “When finalized, we hope that the guidance will support the development of novel therapies that are critically needed to address treatment gaps.” The FDA provides recommendations on data collection, methods to assess treatment response, subject safety and new drug application requirements.  The final version will be the agency’s first guidance about program development and trial design for drugs to treat cocaine use disorder, methamphetamine use disorder and prescription stimulant use disorder. The agency is asking for comments on the draft guidelines within the next 60 days. Some players in the stimulant use disorder treatment space include Sparian Biosciences, which has an early-stage dual sigma receptor antagonist/dopamine transporter inhibitor in development, as well as Myosin Therapeutics, which touts a preclinical small molecule modulator candidate. Both companies have received NIH funding for their work. Beyond the guidance, the FDA has also recently held workshops and public meetings to encourage the development of treatments for stimulant use disorder. 

SBS-518 is a dual sigma receptor antagonist/dopamine active transporter inhibitor in development for the treatment of stimulant use disorder (e.g., cocaine and methamphetamine) Grant awarded by National Institutes of Health / National Institute of Drug Abuse (NIH/NIDA) under the Help End Addiction Long-Term (HEAL) initiative NEW YORK, Aug. 08, 2023 (GLOBE NEWSWIRE) -- Sparian Biosciences, Inc. (“Sparian”), a clinical-stage CNS-focused biopharmaceutical company, today announced that it has been awarded a $19 million, five-year grant to fund development of SBS-518 from IND submission through Phase 1 clinical development. SBS-518 is a first-in-class dual sigma receptor (SR) antagonist/dopamine transporter (DAT) inhibitor in development for the treatment of stimulant use disorder (StUD). StUD is a subset of substance use disorders that includes cocaine and methamphetamine use disorders. The grant was awarded by NIH/NIDA under the Help End Addiction Long-Term (HEAL) initiative. SBS-518 is a novel first-in-class compound that targets within the brain both the sigma receptor (S1 and S2) and the dopamine active transporter (DAT). In pre-clinical efficacy assays, SBS-518 blocks the stimulant induced rise in extra-cellular dopamine and blocks cocaine and methamphetamine self-administration without itself producing self-rewarding behavior. DAT, the site of action for stimulants, including illicit stimulants, has proven to be an elusive target for therapeutics. The combination of sigma and DAT inhibition appears to block the action of methamphetamine and cocaine without interfering with the physiologic transport of dopamine. “Sparian was founded to develop innovative therapeutics to treat CNS disorders, particularly pain and substance use disorders,” said Jeff Reich, M.D., Chief Executive Officer and Co-founder. “StUD presents a major unmet medical and public health need for which there are currently no approved therapies. If we can successfully advance SBS-518 into the clinic, it could represent a significant step forward in the treatment of substance use disorders.” The $19 million dollars in funding represents the third NIH/NIDA grant Sparian has received. Since its founding, Sparian has been awarded a total of $41 million in government grants to support three programs. The lead program SBS1000, a non-opioid analgesic, is now in phase 1 clinical trials. SBS-226, a dual mu opioid receptor (MOR) agonist/delta opioid receptor (DOR) antagonist, is being developed for opioid use disorder (OUD). “We are extremely proud of the ongoing support we have received from NIDA,” said Dr. Reich. “NIDA, through the HEAL initiative, has sparked a new wave of innovation and entrepreneurship dedicated to the treatment of substance use disorders. Sparian, along with our academic partners, is honored to be a trusted collaborator.” SBS-518 is being developed in collaboration with the National Institute of Drug Abuse (NIDA), University of Florida College of Pharmacy, and the Harvard Medical School-McLean Hospital. About Stimulant Use Disorder (StUD) StUD represents a serious public health crisis in the U.S. with a growing prevalence of 4.1 million and approximately 57,000 annual deaths reported in 2021. There are no U.S. Food and Drug Administration-approved drugs to treat StUD. The current treatment approach includes off-label use of prescription therapies, such as antidepressants, and/or behavioral-psychosocial modalities. Only modest benefits have been demonstrated. It is estimated that only 13% of eligible patients are undergoing treatment of any kind reflecting the lack of effective medication. About Sparian Biosciences Sparian Biosciences is a clinical-stage CNS-focused biopharmaceutical company committed to developing transformational therapies to address significant medical needs. The company was co-founded by Jeff Reich, M.D., and Gavril Pasternak, M.D., Ph.D., and was spun out of Memorial Sloan Kettering Cancer Center (MSK). Sparian has five programs that address acute and chronic pain, opioid use disorder (OUD), acute opioid overdose, and stimulant use disorder (StUD). Sparian is the recipient of two NIDA UG3/UH3 grants and an SBIR grant totaling nearly $41M in NIH support. For more information, visit . Research reported in this press release was supported by the National Institute on Drug Abuse of the National Institutes of Health under award number 1UG3DA058553-01.The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health Contact: Annie Pasternak Chief Operating Officer annie@sparianbiosciences.com