Trazodone Hydrochloride

New Data Underscore the Need for New OSA Treatments That Go Beyond Weight Loss to Address the Neuromuscular Root Cause of the DiseaseOral Presentations include Rationale and Design of SynAIRgy Phase 3 Study for AD109, a Potential Nighttime Oral Drug Treatment for OSA“Shining a Light on Living with Sleep Apnea” Symposium Features Premiere Sneak Preview of “Out of Breath” Film Featuring Struggles of Living with OSA, Followed by Panel Discussion CAMBRIDGE, Mass., May 23, 2024 (GLOBE NEWSWIRE) -- Apnimed, Inc., a clinical-stage pharmaceutical company focused on discovery, development and commercialization of novel oral therapies for the treatment of obstructive sleep apnea (OSA) and other sleep disorders, announced a series of five data presentations and a dinner symposium at the SLEEP 2024 annual meeting. Presentations include an epidemiologic study of the prevalence of obesity in OSA, which demonstrates that the majority of people with OSA are not obese. OSA is estimated to affect more than 50 million in the United States, though underdiagnosis continues to be a serious problem. “Apnimed is making significant contributions toward understanding the characteristics of people with OSA and the impact symptoms of OSA have on those who are not being treated. The data being presented at SLEEP 2024 reaffirm that this market has significant unmet needs,” said Larry Miller, MD, CEO of Apnimed. “AD109, our novel oral nighttime drug for OSA, currently in Phase 3 clinical development, has the potential to help patients across a broad spectrum of OSA severity and body mass index by addressing the neuromuscular root cause of OSA. Because there are no FDA approved products that specifically address the neuromuscular causes of OSA, the door is open for an oral therapy that can meet the needs of a broad range of OSA patients.” Additional presentations related to Apnimed’s pipeline of potential OSA treatments include both an oral and a poster discussion concerning the study design and rationale of SynAIRgy, the second Phase 3 registrational study for AD109, and data from the VicTor Study, a Phase 2 crossover study that evaluated an oral combination drug related to Apnimed’s pipeline development candidate AD817. SLEEP, the premier clinical and scientific sleep conference, is a joint meeting of the American Academy of Sleep Medicine (APSS) and the Sleep Research Society. SLEEP 2024, the 38th annual meeting of the APSS, will be held at the George R. Brown Convention Center in Houston from June 1-5. Apnimed SLEEP 2024 Presentation Details: POSTER:P-09, #147Prevalence of Obesity in Obstructive Sleep Apnea within a Large Community-based Cohort of Middled-aged/Older AdultsTime: Monday, June 3, 10:00-10:45 AM CTLocation:George R. Brown Convention Center, Hall A3Presenter:Neda Esmaeili, PhD, Brigham and Women's Hospital POSTER:P-08, #133Fatigue Negatively Impacts the Lives of Individuals Living with OSA: A Closer Look with Patient Reported Outcomes (PRO) MeasuresTime:Monday, June 3, 10:00-10:45 AM CTLocation:George R. Brown Convention Center, Hall A3Presenter:Helene Emsellem, MD, Director, The Center for Sleep & Wake Disorders & Sleep Health Institute SYMPOSIUM:Shining a Light on Living with Sleep ApneaSneak Preview:“Out of Breath,” an independent film about living with OSA followed by a panel discussion with the film’s director and starsTime:Tuesday, June 4, 6:15-8:30PM CTLocation:Marriott Marquis, Houston, Salon A-BRegister:https://bit.ly/3y2gbqe ORAL:O-26Aroxybutynin and Atomoxetine for the Treatment of OSA: Rationale and Design of theSynAIRgy Phase 3 RCTSession:Updates on Non-PAP Therapy for Sleep-Related Breathing DisordersTime: Wednesday, June 5, 2:15-2:30PM CTLocation:George R. Brown Convention Center, Room 362Presenter:Patrick Strollo, Jr., MD, Professor of Medicine and Clinical and Translational Science,Vice Chair of Medicine for Veterans Affairs, University of Pittsburgh School of Medicine POSTER:P-41, #274Aroxybutynin and Atomoxetine for the Treatment of OSA: Rationale and Design of the SynAIRgy Phase 3 RCTTime: Wednesday, June 5, 11:00-11:45 AM CTLocation: George R. Brown Convention Center, Hall A3Presenter:Patrick Strollo, Jr., MD, Professor of Medicine and Clinical and Translational Science, Vice Chair of Medicine for Veterans Affairs, University of Pittsburgh School of Medicine ORAL:O-26The Effect of Viloxazine and Trazodone in Obstructive Sleep Apnea Patients: A Randomized, Placebo-controlled, Crossover StudySession:Updates on Non-PAP Therapy for Sleep-Related Breathing DisordersTime: Wednesday, June 5, 2:30-2:45PM CTLocation:George R. Brown Convention Center, Room 362Presenter:Atqiya Aishah, PhD, Brigham and Women’s Hospital About the SynAIRgy StudyThe SynAIRgy Study (clinicaltrials.gov identifier NCT05813275) is a randomized, double blind, placebo-controlled, parallel-arm 6-month study of a fixed dose combination of aroxybutynin/atomoxetine (AD109) in adult participants with OSA who are intolerant of, or currently refuse, positive airway pressure (PAP) therapy. The SynAIRgy Study examines the use of AD109 in a range of OSA patients across all types of OSA from mild to severe and ranges of body mass index (BMI) from normal to obese. Participants (n=640) will be randomized 1:1 to either AD109 or placebo. The primary endpoint is designed to evaluate reduction of airway obstructions (AHI4) for AD109 vs. placebo. A key secondary endpoint is evaluating OSA symptoms based on the PROMIS-Fatigue scale for AD109 vs. placebo. Other standard objective and subjective metrics of OSA will also be evaluated. The trial also includes an additional cohort of up to 100 participants concomitantly on AD109 and a stable dose of a GLP-1 agonist for weight loss. The trial will include up to 65 enrolling centers across the US and Canada. SynAIRgy is continuing enrollment. Interested participants may check their eligibility at www.sleepapneatrial.com. Topline Phase 3 data for both AD109 registrational trials, LunAIRo and SynAIRgy, are expected in mid-2025. About AD109AD109 has the potential to be the first oral drug that could both treat the underlying nighttime airway obstruction and hypoxia that characterize OSA, as well as improve the daytime consequences of OSA, such as fatigue. It is a potential first-in-class, novel, investigational combination dosed once daily at bedtime and is designed to treat OSA patients across a broad spectrum of disease severity. AD109 combines Apnimed’s novel selective antimuscarinic (aroxybutynin) with a selective norepinephrine reuptake inhibitor (atomoxetine) in a fixed dose combination. AD109 targets key neurological pathways in OSA that activate upper airway dilator muscles to maintain an open airway during sleep. AD109 has the potential to become a safe, effective, and convenient treatment for OSA, addressing some of the key limitations of approved treatments that are often poorly tolerated (e.g., CPAP and oral devices) and/or invasive (e.g., surgery or implanted devices). AD109 has been granted Fast Track designation by the FDA and is currently in Phase 3 clinical trials. About the VicTor StudyThe VicTor Study (clinicaltrials.gov identifier NCT05793684) is a Phase 2 randomized double-blind placebo-controlled multiple-dose 3-period crossover study comparing a fixed dose combination of viloxazine/trazodone to viloxazine alone and to placebo in obstructive sleep apnea. About Obstructive Sleep Apnea Obstructive sleep apnea is one of the most common and serious sleep disorders. It is estimated to affect more than 50 million and as many as 80 million people in the United States, though underdiagnosis continues to be a serious problem and the number of affected Americans may be far greater. OSA impacts people across the spectrum of sex, age, ethnicity and BMI ranges from normal to obese. OSA is characterized by partial or complete upper airway collapse that occurs during sleep, which can cause dramatic reductions in overnight oxygen levels and often leads to poor sleep, and in the long term, has been shown to increase the risk of hypertension, diabetes, cardiovascular disease, and stroke. Additionally, OSA can impair work productivity, reduce daytime functional abilities, and lower quality of life. Sleep-related neuromuscular dysfunction is the key mechanism that causes a reduction in neuromuscular tone of the upper airway during sleep. The vast majority of diagnosed patients are prescribed positive air pressure therapy devices such as continuous positive airway pressure, or CPAP, but many patients are dissatisfied with these mechanical nighttime devices and fewer than half are compliant long term, leaving a significant population untreated or undertreated and at risk. Some OSA patients are overweight or obese, and sustained weight loss can reduce the severity of airway collapse and some symptoms. However, even substantial weight loss may not fully address the symptoms of OSA or reduce the need for treatments that help maintain an open airway during sleep, and if patients regain weight, OSA and its symptoms tend to return. About ApnimedApnimed is a clinical-stage pharmaceutical company working to transform the treatment of sleep apnea based on a simple idea – patients with obstructive sleep apnea could benefit from treatment with a safe and effective oral medication dosed once daily at bedtime. Apnimed’s lead development program, AD109, targets the neurologic control of upper airway muscles to maintain an open airway during sleep. Based in Cambridge, Mass., the company is developing a portfolio of novel pharmacologic therapies for sleep apnea and other sleep disorders. Apnimed has a pipeline of novel, oral pharmacologic programs including several that are part of our Joint Venture with Shionogi & Co., Ltd. called Shionogi-Apnimed Sleep Science, LLC. Learn more at apnimed.com or follow us on X and LinkedIn. Media Contact:Amanda BreedingScient PRamanda@scientpr.com Mikala Whitaker Spectrum Sciencemwhitaker@spectrumscience.com Investor Contact:Brian Ritchie LifeSci Advisorsbritchie@lifesciadvisors.com

Novel compounds protected under Enveric’s intellectual property portfolio provide potential licensing opportunities and non-dilutive revenue streams. CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Enveric Biosciences (NASDAQ: ENVB) (“Enveric” or the “Company”), a biotechnology company dedicated to the development of novel neuroplastogenic small-molecule therapeutics for the treatment of depression, anxiety, and addiction disorders, today announced the discovery of multiple, promising novel compounds sourced using the company’s Psybrary™ platform and proprietary computational chemistry and artificial intelligence (AI) drug-discovery system (PsyAI™). The novel compounds span seven distinct molecule classes totaling at least 57 unique product opportunities, all of which are protected by Enveric’s expansive intellectual property portfolio and represent potential out-licensing opportunities and non-dilutive revenue streams for the Company. Together, the novel and distinct molecule classes broaden and deepen Enveric’s library of assets targeting difficult-to-address mental health disorders, adding to its lead candidate EB-003, a first-in-class neuroplastogen designed to eliminate hallucinations, and EB-002, formerly EB-373, a next generation synthetic prodrug of the active metabolite, psilocin. “Our ability to identify EB-003 and EB-002 as our lead drug candidates was the result of an extensive process in which our research team analyzed more than one thousand compounds spanning numerous classes of molecules, utilizing our proprietary PsyAI and Psybrary platforms,” said Joseph Tucker, Ph.D., Director and CEO of Enveric. “As a result, Enveric now possesses what we believe to be one of the most diverse portfolios of potential drug molecules for the treatment of key, underserved mental health and neurological disorders. Our dedicated approach to protecting our discoveries should enable us to generate significant near- and long-term value for our shareholders via potential partnering and/or licensing agreements.” The novel compounds span seven diverse molecule classes and subclasses, including: Novel Serotonin-Norepinephrine-Dopamine Reuptake Inhibitors (SNDRI) Also known as triple reuptake inhibitors (TRIs), SNDRIs are an emerging class of medications designed to treat severe depression and anxiety disorders. Enveric SNDRI compounds show strong binding to serotonin transporter (SERT), norepinephrine transporter (NET) and dopamine transporter (DAT). Enveric SNDRI compounds also demonstrate distinct additional serotonin receptor binding profiles that bear similarities to those of the antidepressant Nefazodone and the anxiolytic Buspirone. Non-selective Serotonin Reuptake Inhibitor (NSRI) Enveric NSRI compounds show strong binding to SERT, as well as to the 5-HT1A receptor, known to be a therapeutically valuable target. Certain of Enveric’s NSRIs demonstrate additional binding to various serotonin and dopamine family receptors, with binding profiles similar to the antidepressant Vortioxetine and the atypical antipsychotic Aripiprazole. Novel MDMA Derivatives (EMD) Series Twenty novel MDMA derivatives are separated into three subgroups: Strong 5-HT2A receptor binding, Weak 5-HT2A binding, and No 5-HT2A receptor binding. Current literature indicates agonism of the 5-HT2A receptor is linked to hallucination in humans and also to the induction of neuroplasticity. Each subgroup of Enveric’s novel MDMA derivatives demonstrates unique and expanded receptor binding activity targeting adrenergic and/or dopaminergic receptors as well as epinephrine/norepinephrine family receptors. Some of the resulting receptor binding profiles are similar to the anxiolytic Buspirone, the antiepileptic Fenfluramine, the ADHD drug Guanfacine, and the atypical antipsychotic Aripiprazole. Bifunctional Psilocin Prodrugs (BPP) BPPs are readily absorbed, detectable in plasma, and converted to therapeutically relevant levels of plasma psilocin, with demonstrated lower Head Twitch Response (HTR) relative to psilocybin in mice; HTR is reported in the literature to be a predictive indicator for hallucination in humans. Each BPP parent prodrug demonstrates its own unique binding pro serotonin 5-HT1A receptor, 5-HT1B receptor and SERT, with similarities to anxiolytics Buspirone, antidepressant/anxiolytic Flesinoxan, and the antidepressant Paroxetine. Novel Psilocin Prodrug (NPP) Series NPPs are designed to be metabolized to release therapeutic levels of systemic psilocin at varying rates, providing treatment regimen optionality. Included in this series are four compounds that can be converted upon direct intravenous injection to psilocin: potentially bypassing the need for first-pass metabolism, making them amenable to non-oral forms of administration (e.g. intranasal, sublingual, buccal). Melatonin-Receptor Agonist (MRA) Series Melatonin, a natural indolamine, is essential for regulating circadian rhythm in mammals and is often used in to treat a variety of sleep disorders. Enveric MRA compounds demonstrate strong binding to the MT1 Melatonin receptor with some being highly selective for MT1 while others demonstrate expanded target binding profiles similar to the antidepressants Agomelatine, Vortioxetine, Imipramine, and Trazodone. Neuroplastogenic Antidepressant (NAD-01) Designed to induce neuroplasticity and promote long-term therapeutic benefit in patients suffering from severe depressive mood disorders. Demonstrates neuroplastogenic activity comparable to known 5-HT2A receptor agonist N,N-Dimethyltryptamine (DMT). Demonstrates weak 5-HT2A receptor binding affinity and activation. Produces lower Head Twitch Response relative to psilocin and DMT, while promoting recovery of sucrose preference (SP) in stressed mice - an accepted model for evaluation of antidepressant activity. For more information about Enveric’s novel preclinical compounds spanning multiple, distinct classes of molecules, please visit: . About Enveric Biosciences Enveric Biosciences (NASDAQ: ENVB) is a biotechnology company dedicated to the development of novel neuroplastogenic small-molecule therapeutics for the treatment of depression, anxiety, and addiction disorders. Leveraging its unique discovery and development platform, Psybrary™, Enveric has created a robust intellectual property portfolio of New Chemical Entities for specific mental health indications. Enveric’s lead program, EB-003, is a first-in-class approach to the treatment of difficult-to-address mental health disorders designed to promote neuroplasticity without inducing hallucinations in the patient. Enveric is also developing EB-002, formerly EB-373, a next generation synthetic prodrug of the active metabolite, psilocin, being studied as a treatment of psychiatric disorders. Enveric is headquartered in Naples, FL with offices in Cambridge, MA and Calgary, AB Canada. For more information, please visit . Forward-Looking Statements This press release contains forward-looking statements and forward-looking information within the meaning of applicable securities laws. These statements relate to future events or future performance. All statements other than statements of historical fact may be forward-looking statements or information. Generally, forward-looking statements and information may be identified by the use of forward-looking terminology such as “plans,” “expects” or “does not expect,” “proposed,” “is expected,” “budgets,” “scheduled,” “estimates,” “forecasts,” “intends,” “anticipates” or “does not anticipate,” or “believes,” or variations of such words and phrases, or by the use of words or phrases which state that certain actions, events or results may, could, should, would, or might occur or be achieved. Forward-looking statements may include historical statements and statements regarding beliefs, plans, expectations, or intentions regarding the future and are based on the beliefs of management as well as assumptions made by and information currently available to management. Actual results could differ materially from those contemplated by the forward-looking statements as a result of certain factors, including, but not limited to, the ability of Enveric to: carry out successful clinical programs in Australia; achieve the value creation contemplated by technical developments; avoid delays in planned clinical trials; establish that potential products are efficacious or safe in preclinical or clinical trials; establish or maintain collaborations for the development of therapeutic candidates; obtain appropriate or necessary governmental approvals to market potential products; obtain future funding for product development and working capital on commercially reasonable terms; scale-up manufacture of product candidates; respond to changes in the size and nature of competitors; hire and retain key executives and scientists; secure and enforce legal rights related to Enveric’s products, including patent protection; identify and pursue alternative routes to capture value from its research and development pipeline assets; continue as a going concern; and manage its future growth effectively. A discussion of these and other factors, including risks and uncertainties with respect to Enveric, is set forth in Enveric’s filings with the Securities and Exchange Commission, including Enveric’s Annual Report on Form 10-K and its Quarterly Reports on Form 10-Q. Enveric disclaims any intention or obligation to revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.