Drug abuse

Ingelheim, Germany, Oxford and Belfast, UK, April 29, 2025 – Boehringer Ingelheim, the University of Oxford, and Cumulus Neuroscience are joining forces to provide insights into the day-to-day experiences of people living with psychiatric disorders, and how these experiences relate to their brain activity. The first-of-its-kind study will use novel technology to quantify brain activity, mood, and behavior at home in people who have been diagnosed with borderline personality disorder (BPD), an often neglected group of patients. The aims are to explore the acceptability of this technology in patients and gain quantitative, fine-grained, insights that could potentially guide the research and development of much-needed new therapies. Current clinical and lab-based assessments rely on retrospective recall of symptoms. They are thus limited by how accurately patients remember past events and only provide a snapshot in time of an individual’s clinical state. Moreover, self-reported questionnaires lack objectivity. This can lead to an incomplete or inaccurate picture of the overall experience of the individual and the failure of new medicines in clinical studies. This new study aims to change that. It will use Cumulus´ NeuLogiq® neuroassessment platform for the first time in people diagnosed with borderline personality disorder. This platform enables the tracking of brain function over time, both in the clinic, and from the comfort of a study participant’s home. Participants use a tablet to perform gamified versions of established objective behavioral tasks, while wearing the NeuLogiq headset which records EEG (electroencephalogram) brain waves that are precisely time-synced to the tasks. The intent is to capture data that will provide a more accurate picture of brain network activity.  In 2019, one in eight people worldwide were estimated to be living with a mental health condition, and half of the adult population can expect to experience a mental illness by age 75.i,ii*  People diagnosed with severe mental health conditions experience reduced life expectancy relative to the general population, with around 14 years of potential life lost,1 and the economic consequences of mental health conditions can be enormous.iii That’s why Boehringer Ingelheim is embracing ‘Precision Psychiatry’. This in-depth research approach delves into the neurobiology of symptoms with the goal of uncovering more targeted and holistic treatment solutions that address specific symptoms in people living serious mental illness to help them to live fulfilling lives. Kate Saunders, Associate Professor in the Department of Psychiatry of the University of Oxford says, “People diagnosed with borderline personality disorder experience a range of symptoms, including changeable mood, impulsivity, and associated difficulties in interpersonal relationships, all of which can have a significant impact on their lives. We're looking forward to exploring this new technology in people living with BPD, in collaboration with the scientists at Cumulus and Boehringer Ingelheim, to gain new insights into the mechanisms which underpin the symptoms people given this diagnosis experience.  This could open up pathways for the development of new therapies.” Dr. Hugh Marston, Senior Vice President and Global Head Neuroscience & Mental Health, Boehringer Ingelheim says, “Boehringer Ingelheim is committed to developing novel therapeutics to address the major unmet needs of people living with mental health disorders. If this platform is successfully validated in this patient population, it could be a game-changer for studies investigating novel precision psychiatry treatments. It could help us identify biomarkers for stratification and provide a rich dataset for reverse-translation.” “Many psychiatric conditions disrupt cognitive function, meaning that patients may find it harder to manage their daily life or continue to work effectively,” said Brian Murphy, PhD, Co-founder and Chief Scientific Officer of Cumulus. “These underappreciated symptoms can change from day to day, so frequent real-world measurement is important if we want to find new therapies that improve activities of daily living and quality of life. Today, we are fortunate that wearable technologies and AI are enabling a new era of drug development where we can understand objectively how a drug affects cognitive function and the underlying brain mechanisms that drive it.”  The study will be conducted by the Department of Psychiatry of the University of Oxford at the Warneford Hospital. It will frequently collect EEG and behavioral assessments, alongside remote measures of mood and activity. The main aims are to assess the feasibility of using the Cumulus platform in young adults aged 18-35 and to provide a rich dataset about brain activity and behavior in BPD for in-depth analysis.  Thirty participants who have been diagnosed with BPD and 20 participants with no diagnosed mental health disorder will be recruited. Dr. Lauren Atkinson, from the Department of Psychiatry who will be senior researcher on the study says, “We are looking forward to working with people diagnosed with borderline personality disorder and prioritising research important to them. One of the key features of a BPD diagnosis is affective dysregulation. By regularly capturing mood, alongside measures of brain activity and cognitive function over an extended period of time, we hope to better capture patient experience and use objective measures to understand more about what is happening at those key moments.” *The mental health conditions studied in this epidemiological research included: panic disorder and/or agoraphobia, generalized anxiety disorder, post-traumatic stress disorder, social phobia, specific phobia, major depressive disorder, bipolar disorder, alcohol abuse disorder, alcohol dependence disorder, drug abuse disorder, drug dependence disorder, attention deficit/hyperactivity disorder, and intermittent explosive disorder.About Boehringer Ingelheim Boehringer Ingelheim is a biopharmaceutical company active in both human and animal health. As one of the industry’s top investors in research and development, the company focuses on developing innovative therapies that can improve and extend lives in areas of high unmet medical need. Independent since its foundation in 1885, Boehringer takes a long-term perspective, embedding sustainability along the entire value chain. Our approximately 54,500 employees serve over 130 markets to build a healthier and more sustainable tomorrow. Learn more at www.boehringer-ingelheim.com (global) or www.boehringer-ingelheim.com/uk (UK). About Cumulus Neuroscience Our mission is to generate the data and insights required to accelerate the diagnosis and management of central nervous system (CNS) disorders for millions of patients and caregivers around the world. At Cumulus Neuroscience we are advancing NeuLogiq®, an AI-based, multi-domain digital biomarker platform designed with 10 of the world's leading pharma companies. This novel platform provides the critical data and insights needed for faster, more robust and cost-effective decision-making in clinical trials and patient care. NeuLogiq enables study sponsors to capture large amounts of real-world clinical data repeatedly over time, across multiple behavioral and physiological domains, in the clinic and at home. Together with machine learning (ML) analytics, Cumulus simplifies and improves the robustness of CNS clinical trials, providing objective assessment of study inclusion and treatment outcomes. About Oxford University The University Department of Psychiatry’s mission is to conduct world-class research, teach psychiatry to medical students, develop future researchers in a graduate programme, teach doctors in training, promote excellence in clinical practice, and develop and provide innovative clinical services. It supports research in four key areas: neurobiology, psychological treatments, developmental psychiatry and social psychiatry. The Department is committed to the translation of scientific discovery into benefits for patients. www.psych.ox.ac.uk  Oxford University has been placed number 1 in the Times Higher Education World University Rankings for the ninth year running, and ​number 3 in the QS World Rankings 2024. At the heart of this success are the twin-pillars of our ground-breaking research and innovation and our distinctive educational offer. Oxford is world-famous for research and teaching excellence and home to some of the most talented people from across the globe. Our work helps the lives of millions, solving real-world problems through a huge network of partnerships and collaborations. The breadth and interdisciplinary nature of our research alongside our personalised approach to teaching sparks imaginative and inventive insights and solutions. Through its research commercialisation arm, Oxford University Innovation, Oxford is the highest university patent filer in the UK and is ranked first in the UK for university spinouts, having created more than 300 new companies since 1988. Over a third of these companies have been created in the past five years. The university is a catalyst for prosperity in Oxfordshire and the United Kingdom, contributing £15.7 billion to the UK economy in 2018/19, and supports more than 28,000 full time jobs. Media Contacts  Boehringer Ingelheim: Dr. Reinhard Malin Boehringer Ingelheim Corporate Center GmbH  Innovation Unit/Bio Comms, Corp. Affairs  Media + PR  press@boehringer-ingelheim.com  Cumulus:Tina Sampath tina.sampath@cumulusneuro.com Oxford University: Lisa Jones Communications Manager Department of Psychiatry, University of Oxford, Warneford Hospital lisa.jones@psych.ox.ac.uk 

Centers for Disease Control and Prevention (the "CDC") reported 105,007 drug overdose deaths - with 90% involving synthetic opioids like fentanyl Mazindol ER potentially offers a non-opioid alternative, addressing the underlying neurochemical imbalances associated with fentanyl addiction. Mazindol ER is patent protected beyond September 2038 ZURICH, Jan. 28, 2025 /PRNewswire/ -- NLS Pharmaceutics Ltd. (NASDAQ: NLSP) (NASDAQ: NLSPW) ("NLS" or the "Company"), a Swiss clinical-stage biopharmaceutical company dedicated to developing therapies for rare and complex central nervous system disorders, is proud to announce the launch of a preclinical program evaluating Mazindol ER (Extended-Release) as a novel treatment for fentanyl dependence. Fentanyl dependence is a major global health crisis and was recently declared a national public health emergency by the new Trump administration. In 2023, the CDC reported 105,007 drug overdose deaths with 90% involving synthetic opioids like fentanyl. "The opioid epidemic, and specifically the rise of fentanyl dependence, presents an urgent medical need for innovative, non-opioid treatment approaches," said Alex Zwyer, Chief Executive Officer of NLS. "We are committed to exploring the unique pharmacological profile of Mazindol, which targets multiple neurotransmitter systems implicated in opioid addiction. This preclinical program represents an important step in developing a potentially transformative therapy." Highlights of the Preclinical Program Mazindol, a tetracyclic compound with a distinct pharmacological profile, has shown potential in mitigating opioid dependence by acting on multiple neurotransmitter pathways, including: 5-HT1A receptor modulation: Regulates mood, anxiety, and reward pathways, addressing psychological aspects of opioid withdrawal. Mu-opioid receptor ("MOP") interaction: Provides partial modulation of opioid effects, potentially reducing cravings and withdrawal symptoms without reinforcing addiction. Orexin-2 receptor ("OX2R") partial agonist: Aids in restoring sleep-wake cycles and enhancing cognitive stability, which are significantly disrupted during opioid withdrawal. Scientific Rationale Fentanyl, a synthetic opioid that is up to 50 times more potent than heroin, has driven a global health crisis due to its high abuse potential and severe withdrawal symptoms. Traditional treatments, such as methadone and buprenorphine, often come with limitations, including risk of dependence and regulatory hurdles. Mazindol ER offers a potential non-opioid alternative, addressing the underlying neurochemical imbalances associated with fentanyl addiction while supporting recovery through its multimodal action on neurotransmitter systems. The sustained-release formulation provides a long-acting therapeutic effect, improving patient compliance and minimizing withdrawal-related disruptions. Mechanism of Action of Mazindol ER Mazindol's unique pharmacodynamic properties position it as a promising candidate for opioid dependence treatment. Its mechanisms include: Inhibition of dopamine and norepinephrine transporters, restoring neurochemical balance and reducing cravings. 5-HT1A receptor modulation, potentially alleviating anxiety and depressive symptoms associated with withdrawal. MOP agonist activity, which may help mitigate opioid withdrawal symptoms while preventing full opioid reinforcement. Partial OX2R agonist activity, aiding in circadian rhythm regulation and reducing the impact of opioid-induced sleep disturbances. Preclinical Study Objectives and Next Steps The preclinical study, designated Study KO-943, will focus on: Evaluating the safety and efficacy of Mazindol ER in fentanyl dependence models. Assessing pharmacokinetics and pharmacodynamics in opioid-exposed subjects. Exploring the impact of Mazindol ER on craving reduction, withdrawal mitigation, and cognitive performance. The study is expected to be completed within 12-18 months. Upon successful results, NLS will potentially seek regulatory pathways to advance to clinical development. "We believe that Mazindol ER could offer a paradigm shift in opioid addiction treatment," added Dr. Konofal, M.D./PhD, Chief Scientific Officer of NLSP. "Our stepwise development plan prioritizes early-stage investment to generate critical data that will pave the way for larger-scale studies and potential commercialization opportunities." Existing Patent Portfolio NLS Pharmaceutics has secured several patents supporting the development of Mazindol ER: United States Patent No. 11,207,271: Covers oral formulations containing immediate-release and sustained-release layers of mazindol and their use in treating attention deficit disorders ("ADHD") as well as sleep disorders. United States Patent No. 11,596,622: Granted for the use of Mazindol ER in the treatment of heroin dependence, providing a new therapeutic strategy for opioid use disorder. These patents strengthen the Company's intellectual property position and support the ongoing development of Mazindol ER for various indications. Future Outlook NLS aims to utilize initial findings to expanded research and potential commercialization of Mazindol ER in the treatment of fentanyl dependence. Other pipeline candidates include: NLS-4 (Lauflumide): A wake-promoting agent with applications in military and emergency response. NLS-11 (Benedin): A circadian rhythm modulator with potential applications for space missions and the ultra-rare Kleine-Levin Syndrome (KLS). NLS-3 (Levophacetoperane SR): A novel treatment for ADHD and Autism Spectrum Disorders, with potential pro-drug development. 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. NLS has recently filed a Registration Statement on Form F-4 with the U.S. Securities and Exchange Commission (the "SEC"), outlining the details of the proposed merger between NLS and Kadimastem (the "Merger"). Kadimastem is a leading clinical stage cell therapy company, developing "off-the-shelf", proprietary cell products including human pancreatic islet-like cells capable of secreting insulin to generate an innovative treatment intended for the potential cure of type 1 diabetes. Following the Merger, NLS and Kadimastem expect to continue developing NLS's promising, first-in class Dual Orexin Agonist platform within the combined company. The remaining NLS assets are expected to be divested subject to a contingent value rights agreement, the proceeds of which will be distributed entirely to the current shareholders of NLS. For more information, please visit . About Kadimastem Kadimastem is a clinical stage cell therapy company, developing "off-the-shelf", allogeneic, proprietary cell products based on its technology platform for the expansion and differentiation of Human Embryonic Stem Cells (hESCs) into functional cells. AstroRx®, the company's lead product, is an astrocyte cell therapy in clinical development for the treatment for ALS and in pre-clinical studies for other neurodegenerative indications. IsletRx is the company's treatment for diabetes. IsletRx is comprised of functional pancreatic islet cells producing and releasing insulin and glucagon, intended to treat and potentially cure patients with insulin-dependent diabetes. Kadimastem was founded by Professor Michel Revel, Chief Scientific Officer of Kadimastem and Professor Emeritus of Molecular Genetics at the Weizmann Institute of Science. Professor Revel received the Israel Prize for the invention and development of Rebif®, a multiple sclerosis blockbuster drug sold worldwide. Kadimastem is traded on the Tel Aviv Stock Exchange (TASE: KDST). 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 use of Mazindol as a potential novel treatment for fentanyl dependence, regulatory approval timelines, clinical trial outcomes, market acceptance and its expected preclinical program. Further, NLS and Kadimastem are using forward-looking statements when they discuss the expected closing of the transaction and the potential benefits of the transaction to NLS and Kadimastem and their respective shareholders, as well as the expected strategic position of the combined company following the merger, if completed. These forward-looking statements and their implications are based on the current expectations of the management of NLS and Kadimastem 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: risks related to the combined company's or NLS's ability to have future successful meetings with the FDA; risks related to the companies' ability to complete the merger on the proposed terms and schedule, including risks and uncertainties related to the satisfaction of the closing conditions related to the merger agreement and risks and uncertainties related to the failure to timely, or at all, obtain shareholder approvals for the transaction; unexpected costs, charges or expenses resulting from the transaction and potential adverse reactions or changes to business relationships resulting from the announcement or completion of the proposed merger or resulting from the trial or preclinical program and potential adverse reactions or changes to business relationships resulting from the announcement of the trial or preclinical program; changes in technology and market requirements; either or both companies may encounter delays or obstacles in launching and/or successfully completing their clinical trials; the companies' products may not be approved by regulatory agencies; their technologies may not be validated as they progress and their methods may not be accepted by the scientific community; either of both of the companies may be unable to retain or attract key employees whose knowledge is essential to the development of their products; unforeseen scientific difficulties may develop with the products being advanced by the companies; their products may wind up being more expensive than anticipated; 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; the companies' patents may not be sufficient; their products may harm recipients; changes in legislation may adversely impact either or both of the companies; 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 candidate products to differ materially from those contemplated in such forward-looking statements. Except as otherwise required by law, neither Kadimastem nor NLS undertakes any 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's annual report on Form 20-F for the year ended December 31, 2023, filed with the SEC, which is available on the SEC's website, , and in subsequent filings made by NLS with the SEC, including under the heading "Risk Factors" in NLS's registration statement on Form F-4, filed with the SEC on December 27, 2024. No Offer or Solicitation This communication is not intended to and shall not constitute an offer to buy or sell or the solicitation of an offer to buy or sell any securities, or a solicitation of any vote or approval, nor shall there be any sale of securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such jurisdiction. No offering of securities shall be made, except by means of a prospectus meeting the requirements of Section 10 of the Securities Act of 1933, as amended. Additional Information about the Transaction and Where to Find It In connection with the proposed transaction, NLS has filed a Registration Statement on Form F-4, including a proxy statement/prospectus, with the SEC. NLS may also file other relevant documents with the SEC regarding the proposed transaction. This document is not a substitute for the proxy statement/prospectus or any other document that NLS may file with the SEC. The proxy statement (if and when available) will be mailed or delivered to shareholders of NLS and Kadimastem. INVESTORS AND SECURITY HOLDERS ARE URGED TO READ THE PROXY STATEMENT/PROSPECTUS AND ANY OTHER RELEVANT DOCUMENTS THAT MAY BE FILED WITH THE SEC, AS WELL AS ANY AMENDMENTS OR SUPPLEMENTS TO THESE DOCUMENTS, CAREFULLY AND IN THEIR ENTIRETY IF AND WHEN THEY BECOME AVAILABLE BECAUSE THEY CONTAIN OR WILL CONTAIN IMPORTANT INFORMATION ABOUT THE PROPOSED TRANSACTION. Investors and security holders will be able to obtain free copies of the proxy statement/prospectus (if and when available) and other documents containing important information about NLS and Kadimastem and the proposed transaction, once such documents are filed with the SEC through the website maintained by the SEC at . Copies of the documents filed with the SEC by the Company will be available free of charge on NLS's website at . Participants in the Solicitation NLS, Kadimastem, and certain of their respective directors and executive officers may be deemed to be participants in the solicitation of proxies from NLS and Kadimastem shareholders in respect of the proposed transaction. Information about the directors and executive officers of NLS, including a description of their direct or indirect interests, by security holdings or otherwise, is set forth in NLS's Annual Report on Form 20-F for the fiscal year ended December 31, 2023, which was filed with the SEC on May 15, 2024. Other information regarding the participants in the proxy solicitation and a description of their direct and indirect interests, by security holdings or otherwise, will be contained in the proxy statement/prospectus and other relevant materials to be filed with the SEC regarding the proposed merger when such materials become available. Investors should read the proxy statement/prospectus carefully when it becomes available before making any voting or investment decisions. You may obtain free copies of these documents from NLS Pharmaceutics using the sources indicated above. NLS Contacts: [email protected] Kadimastem Contacts: Sarah Bazak, Investors relations [email protected] SOURCE NLS Pharmaceutics Ltd. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

FRIDAY, Dec. 6, 2024 -- Pregnancy can be a trying time for women at best, but new research shows that 1 in every 20 pregnant American women also suffer physical, sexual or emotional abuse. Abuse can take a toll on the mental and physical health of the mom-to-be and her baby, because it's strongly linked to "delayed prenatal care, depression and post-traumatic stress disorder [PTSD]," the research team wrote. The new study also showed that abuse experienced in pregnancy can raise risks for maternal substance abuse, premature delivery and low birth weight. The research was led by Megan Steele-Baser , of the Division of Violence Prevention at the U.S. Centers for Disease Control and Prevention. Her team looked at 2016-2022 data on self-reported levels of physical or sexual violence and emotional abuse for pregnant women living in Arkansas, the District of Columbia, Indiana, Kansas, Mississippi, Pennsylvania, South Dakota, Washington and Wisconsin. Women were also asked about the state of their health and health care during the pregnancy. The data showed that more than 1 in every 20 of the women (5.4%) had some experience of abuse from an intimate parter during their pregnancy. Emotional abuse (denigrating comments, yelling and other abuse) was most common, with 5.2% of women citing these experiences, while 1.5% of women suffered physical violence from a partner and 1% cited sexual violence. All of this could seriously impact pregnancy outcomes. For example, experiencing emotional abuse was linked to a near-tripling of the risk for depression during pregnancy, and it greatly raised the odds that a mom-to-be would smoke or use alcohol or marijuana. Physical violence inflicted on a pregnant women upped her chances of depression nearly three-fold, and it raised her chances for gestational high blood pressure by 30% and preterm birth by 50%, the research showed. Sometimes, outcomes can be fatal: According to Steele-Baser and colleagues, 40% of homicides affecting pregnant women coincide with intimate partner violence. The researchers also noted that suicide, drug overdose and other forms of fatalities linked to mental health issues remain the leading cause of death for pregnant women. All may be linked to depression , which can easily arise in the context of abuse by an intimate partner. According to Steele-Baser's team, more can and must be done to prevent these tragedies. "Addressing multiple intimate partner violence types through comprehensive prevention efforts is critical to supporting maternal ad infant health," they wrote. The new findings were published Dec. 5 in the CDC journal Morbidity and Mortality Weekly Report . Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.