NMDA receptor

SOUTH SAN FRANCISCO, Calif.--( BUSINESS WIRE )-- Vistagen (Nasdaq: VTGN) a late clinical-stage neuroscience-focused biopharmaceutical company dedicated to the development and commercialization of groundbreaking therapies for psychiatric and neurological disorders based on nose-to-brain neurocircuitry, today announced enrollment of the first subject in its PALISADE-4 Phase 3 trial of fasedienol, an investigational neuroactive pherine nasal spray in U.S. registration-directed Phase 3 development for the acute treatment of social anxiety disorder (SAD). “With the initiation of PALISADE-4 as planned, we have achieved another important milestone in our registration-directed PALISADE Phase 3 program for fasedienol, which has potential to deliver a transformative acute treatment option to over 30 million Americans suffering from the debilitating effects of SAD, including increased risk for depression, alcohol abuse, and suicide attempts,” said Shawn Singh, Chief Executive Officer of Vistagen. “Current pharmacological therapies approved by the U.S. FDA do not include an acute treatment option. With pioneering neuroscience, we are breaking new ground in the development of a treatment for SAD with our novel product candidate designed for non-systemic, rapid activation of nose-to-brain neural circuits to reduce fear and anxiety associated with SAD.” About Vistagen’s PALISADE Phase 3 Program for Fasedienol for the Acute Treatment of SAD Vistagen's U.S. registration-directed PALISADE Phase 3 development program for fasedienol for the acute treatment of SAD includes the ongoing PALISADE-3 and PALISADE-4 Phase 3 trials, each a randomized, double-blind, placebo-controlled Phase 3 trial designed to evaluate the efficacy, safety, and tolerability of the acute administration of fasedienol to relieve anxiety symptoms in subjects with SAD induced by a public speaking challenge conducted in a clinical setting. PALISADE-3 and PALISADE-4 are designed similarly to Vistagen’s PALISADE-2 Phase 3 trial of fasedienol, from which positive data was reported last year. The primary outcome measure in each of the PALISADE Phase 3 trials is a subject’s self-rated Subjective Units of Distress Scale (SUDS). Similar to PALISADE-3 initiated earlier this year, the PALISADE-4 Phase 3 U.S. multi-center trial is planned to randomize approximately 236 adults aged 18 through 65. Subjects will be randomized in a 1:1 ratio to fasedienol or placebo. PALISADE-3 and PALISADE-4 also include open-label extension phases to evaluate the safety and tolerability of ongoing use of fasedienol in a real-world setting over a period of up to 12 months. Vistagen believes either PALISADE-3 or PALISADE-4, if successful, together with PALISADE-2, may establish substantial evidence of the effectiveness of fasedienol in support of a potential fasedienol New Drug Application (NDA) submission to the FDA for the acute treatment of SAD. About Fasedienol Nasal Spray Fasedienol is a potential first-in-class, investigational neuroactive pherine nasal spray designed to have rapid onset with a novel proposed mechanism of action (MOA) that is differentiated from all currently approved anxiety medications. Fasedienol is designed to regulate the olfactory-amygdala neural circuits of fear and anxiety and attenuate the tone of the sympathetic autonomic nervous system, without systemic absorption, potentiation of GABA-A receptors, or direct activity on neurons in the brain. Vistagen’s U.S. registration-directed PALISADE Phase 3 program for fasedienol is focused on the acute treatment of SAD. Fasedienol has not demonstrated any signals of abuse potential or suggested any potential for psychological and physical dependence in any clinical trial conducted to date. There is no U.S. FDA-approved acute treatment for SAD. The U.S. FDA has granted Fast Track designation for the investigation of fasedienol for the acute treatment of SAD. About Social Anxiety Disorder Social anxiety disorder (SAD) affects over 30 million Americans. A person with SAD feels intense, persistent, and sometimes disabling symptoms of anxiety or fear in certain social situations, such as meeting new people, making comments in a business meeting, dating, being on a job interview, answering a question in class, or talking to a cashier in a store. Doing common, everyday things in front of people causes profound anxiety or fear of being embarrassed, evaluated, humiliated, judged, or rejected. SAD can get in the way of going to work, attending school, or doing a wide variety of things in a situation likely to involve interpersonal interaction. It can lead to avoidance and opportunity costs that can significantly impact a person's employment and social activities and can be very disruptive to their overall quality of life. There is no U.S. FDA-approved acute treatment for SAD. About Vistagen Headquartered in South San Francisco, CA, Vistagen (Nasdaq: VTGN) is a late clinical-stage neuroscience-focused biopharmaceutical company dedicated to the development and commercialization of groundbreaking therapies for psychiatric and neurological disorders based on its pioneering approach and deep understanding of nose-to-brain neurocircuitry. Vistagen’s diversified pipeline of pherine product candidates is designed exclusively as nasal sprays administered at microgram level doses to rapidly activate chemosensory neurons in the nasal cavity with novel non-systemic proposed mechanisms of action designed to impact the olfactory system and brain neurocircuitry to achieve diverse therapeutic effects. Favorable safety data have been generated in all clinical studies of Vistagen’s pherine product candidates completed to date. Vistagen’s neuroscience pipeline also includes an oral prodrug with the potential to modulate NMDA receptor activity in certain neurological conditions, such as levodopa-induced dyskinesia associated with Parkinson’s disease therapy and neuropathic pain. At Vistagen, we are passionate about creating novel and differentiated treatments that set new standards of care for millions of people living with anxiety, depression, and other neurological disorders. Connect at www.Vistagen.com . Forward-looking Statements This press release contains certain forward-looking statements within the meaning of the federal securities laws. These forward-looking statements involve known and unknown risks that are difficult to predict and include all matters that are not historical facts. In some cases, you can identify forward-looking statements by the use of words such as “may,” “could,” “expect,” “project,” “outlook,” “strategy,” “intend,” “plan,” “seek,” “anticipate,” “believe,” “estimate,” “predict,” “potential,” “strive,” “goal,” “continue,” “likely,” “will,” “would” and variations of these terms and similar expressions, or the negative of these terms or similar expressions. Such forward-looking statements are necessarily based upon estimates and assumptions that, while considered reasonable by Vistagen and its management, are inherently uncertain. As with all pharmaceutical products, there are substantial risks and uncertainties in the process of development and commercialization and actual results or developments may differ materially from those projected or implied in these forward-looking statements. Among other things, there can be no guarantee that any of Vistagen’s drug candidates will successfully complete ongoing or future clinical trials, receive regulatory approval or be commercially successful, or that Vistagen will be able to successfully replicate the result of past studies of its product candidates, including fasedienol, itruvone, PH80 or its other drug candidates. Other factors that may cause such a difference include, without limitation, risks and uncertainties relating to conducting and/or completing ongoing clinical trials, including PALISADE-3 and/or PALISADE-4; launching planned clinical trials for any of our product candidates, including fasedienol; Vistagen’s submission of a new drug application (NDA) to the U.S. FDA for any product candidate, including fasedienol; the ability of any clinical trial information submitted by the Company to the U.S. FDA to support a NDA; the scope and enforceability of Vistagen’s patents, including patents related to Vistagen’s pherine drug candidates and AV-101; fluctuating costs of materials and other resources and services required to conduct Vistagen’s ongoing and/or planned clinical and non-clinical trials; market conditions; the impact of general economic, industry or political conditions in the United States or internationally; and other technical and unexpected hurdles in the development, manufacture and commercialization of Vistagen’s product candidates. These risks are more fully discussed in the section entitled “Risk Factors” in Vistagen’s most recent Annual Report on Form 10-K for the fiscal year ended March 31, 2024, and Quarterly Report on Form 10-Q for the period ended June 30, 2024, as well as discussions of potential risks, uncertainties, and other important factors in our other filings with the U.S. Securities and Exchange Commission (SEC). Vistagen’s SEC filings are available on the SEC’s website at www.sec.gov . You should not place undue reliance on these forward-looking statements, which apply only as of the date of this press release and should not be relied upon as representing Vistagen’s views as of any subsequent date. Vistagen explicitly disclaims any obligation to update any forward-looking statements other than as may be required by law. If Vistagen does update one or more forward-looking statements, no inference should be made that Vistagen will make additional updates with respect to those or other forward-looking statements.

Second Phase 2 Study for Luvadaxistat Fails to Meet Primary Endpoint as Potential Treatment for Cognitive Impairment Associated with Schizophrenia Results Confounded by Variability in Cognition Measures Across Population Studied and Potential Imbalance in Baseline Characteristics of Enrolled Subjects Neurocrine Biosciences to Focus Resources on Phase 3 Clinical Development of NBI-1117568 for Schizophrenia and NBI-1065845 for Major Depressive Disorder SAN DIEGO , Sept. 12, 2024 /PRNewswire/ -- Neurocrine Biosciences, Inc. (Nasdaq: NBIX) today announced that its ERUDITE™ Phase 2 clinical study of investigational compound luvadaxistat (NBI-1065844) failed to meet its primary endpoint as a potential treatment to improve cognitive impairment in patients with schizophrenia. The ERUDITE study was the second Phase 2 trial for luvadaxistat. It failed to replicate the cognitive endpoints data seen in the earlier INTERACT™ study, due in part to the large variability seen in the cognitive measures across the population studied and a potential imbalance in the baseline characteristics of subjects enrolled across the treatment arms. In the INTERACT study, 50 mg luvadaxistat resulted in a statistically significant improvement in measure of cognition on the Brief Assessment of Cognition in Schizophrenia (BACS) and cognitive performance on the Schizophrenia Cognition Rating Scale (SCoRS). The INTERACT study represented the first time statistical significance had been demonstrated for both cognitive measure and function within a single study. “While it’s disappointing that luvadaxistat did not meet the primary endpoint in this study, we understand the challenges and hurdles that exist in identifying potential medicines for the treatment of cognitive impairment in schizophrenia. We therefore plan to halt further development of luvadaxistat at this time and instead will focus our efforts and resources on the advancement into Phase 3 clinical development of NBI-1117568 for schizophrenia and NBI-1065845 for major depressive disorder,” said Eiry W. Roberts, M.D., Chief Medical Officer. “We are excited by the opportunity that lies ahead of us to bring forward potential medicines for patients in these important areas of unmet need in neuropsychiatry.” About Luvadaxistat Luvadaxistat (NBI-1065844) is an investigational, oral, selective inhibitor with a high binding affinity to d-amino acid oxidase (DAAO), which metabolizes D-Serine, a primary NMDA receptor co-agonist in the limbic region of the brain. In schizophrenia, N-methyl D-aspartate (NMDA) receptor hypofunction on PV + gamma-aminobutyric acid (GABA) interneurons results in disinhibition of cortical or hippocampal glutamate neurons projecting to the pyramidal neurons, which are associated with cognitive impairment seen in schizophrenia. The ERUDITE™ Phase 2 clinical study is a randomized, double-blind, placebo-controlled, parallel group study to evaluate the efficacy safety and tolerability of luvadaxistat in adults with cognitive impairment associated with schizophrenia (CIAS). For more information about this study, visit ClinicalTrials.gov . Neurocrine Biosciences acquired the rights to develop and commercialize luvadaxistat from Takeda Pharmaceutical Company, Ltd. About Schizophrenia Schizophrenia is a serious and complex syndrome with heterogeneous symptoms. This chronic and disabling mental health condition is thought to result from a complex interplay of genetic and environmental risk factors. The World Health Organization estimates that the disorder impacts more than 20 million people worldwide. Annual associated costs for schizophrenia are estimated to be more than $150 billion in the United States . It is estimated that approximately 80 percent of people living with schizophrenia have cognitive impairment associated with schizophrenia (CIAS). About Neurocrine Biosciences Neurocrine Biosciences is a leading neuroscience-focused, biopharmaceutical company with a simple purpose: to relieve suffering for people with great needs, but few options. We are dedicated to discovering and developing life-changing treatments for patients with under-addressed neurological, neuroendocrine and neuropsychiatric disorders. The company’s diverse portfolio includes FDA-approved treatments for tardive dyskinesia, chorea associated with Huntington’s disease, endometriosis* and uterine fibroids*, as well as a robust pipeline including multiple compounds in mid- to late-phase clinical development across our core therapeutic areas. For three decades, we have applied our unique insight into neuroscience and the interconnections between brain and body systems to treat complex conditions. We relentlessly pursue medicines to ease the burden of debilitating diseases and disorders, because you deserve brave science. For more information, visit neurocrine.com , and follow the company on LinkedIn , X (formerly Twitter) , and Facebook . (* in collaboration with AbbVie) The NEUROCRINE BIOSCIENCES Logo Lockup and YOU DESERVE BRAVE SCIENCE are registered trademarks of Neurocrine Biosciences, Inc. INTERACT and ERUDITE are trademarks of Neurocrine Biosciences, Inc. Forward-Looking Statements In addition to historical facts, this press release contains forward-looking statements that involve a number of risks and uncertainties. These statements include, but are not limited to, statements related to the clinical results from, and our future development plans with respect to luvadaxistat. Among the factors that could cause actual results to differ materially from those indicated in the forward-looking statements are: risks that clinical development activities may not be initiated or completed on time or at all, or may be delayed for regulatory, manufacturing, or other reasons, may not be successful or replicate previous clinical trial results, may fail to demonstrate that our product candidates are safe and effective, or may not be predictive of real-world results or of results in subsequent clinical trials; our future financial and operating performance; risks associated with our dependence on third parties for development, manufacturing, and commercialization activities for our products and product candidates, and our ability to manage these third parties; risks that the FDA or other regulatory authorities may make adverse decisions regarding our products or product candidates; risks that the potential benefits of the agreements with our collaboration partners may never be realized; risks that our products, and/or our product candidates may be precluded from commercialization by the proprietary or regulatory rights of third parties, or have unintended side effects, adverse reactions or incidents of misuse; risks associated with U.S. federal or state legislative or regulatory and/or policy efforts which may result in, among other things, an adverse impact on our revenues or potential revenue; risks associated with potential generic entrants for our products; and other risks described in the Company’s periodic reports filed with the Securities and Exchange Commission, including without limitation the Company’s quarterly report on Form 10-Q for the quarter ended June 30, 2024 . Neurocrine Biosciences disclaims any obligation to update the statements contained in this press release after the date hereof other than required by law. View original content to download multimedia: SOURCE Neurocrine Biosciences, Inc.

- Radiprodil appeared to be generally well-tolerated in patients with gain-of-function (GoF) variants in GRIN genes, both with and without countable motor seizures (CMS) at baseline - Patients with CMS saw a median reduction of 86% in seizure frequency from baseline, over and above background anti-seizure medications, with 71% experiencing a greater than 50% reduction - Results are expected to support planned discussions with regulators to potentially advance radiprodil to a Phase 3 pivotal trial - GRIN Therapeutics is backed by a $200 million capital commitment from Blackstone Life Sciences NEW YORK, Sept. 9, 2024 /PRNewswire/ -- GRIN Therapeutics, Inc., a leader in the development of therapies to treat serious neurodevelopmental disorders, reported topline results from the Company's ongoing two-part global Phase 1b open-label trial evaluating the safety, tolerability, pharmacokinetics, and efficacy of radiprodil, an investigational, selective and potent negative allosteric modulator of the N-methyl-D-aspartate receptor subtype 2B (NR2B or GluN2B), in the treatment of GRIN-related neurodevelopmental disorder. The results were presented in a podium presentation yesterday at the International League Against Epilepsy (ILAE) 15th European Epilepsy Conference in Rome, Italy. "The results of this trial are very encouraging as they suggest that radiprodil has the potential to substantially reduce the occurrence of seizures and possibly improve behaviors in children with gain-of-function mutations who are not responding well to current treatments," said Prof. Renzo Guerrini, MD, FRCP, FAES, Director, Neuroscience and Human Genetics Department, Phase 1 Clinical Trial Centre, Children's Hospital A. Meyer IRCCS, University of Florence, Italy. "Given these initial efficacy data and promising safety profile, we look forward to continuing to advance this important research program into the next phase of development." The Honeycomb study enrolled 15 pediatric patients with confirmed GoF mutations in the GRIN1, GRIN2A, or GRIN2B genes. The primary objectives of the study were to assess the safety and pharmacokinetics of radiprodil, while key secondary objectives focused on evaluating efficacy on both seizures and non-seizure outcomes. At study enrollment, patients were divided into two cohorts based on the frequency of countable motor seizures (CMS) they experienced during a 28-day screening period (Cohort 1) and baseline severity of non-seizure behavioral symptoms (Cohort 2). Following screening and observation periods, patients were escalated from a starting dose level of 0.05 mg/kg based on tolerability, pharmacokinetics, and predicted GluN2B receptor occupancy to a dose level to be maintained through an eight-week maintenance period. Part B of the Honeycomb study, an open-label extended treatment period for patients who completed Part A and were eligible for continued study treatment, remains ongoing. As of the July 15 data cut, 15 patients were available for analysis. Demographics and baseline disease characteristics were representative of the targeted GRIN population and generally balanced between the seizure (Cohort 1) and non-seizure behavior (Cohort 2) cohorts. There was a high level of seizure activity at baseline in Cohort 1 with a mean of 37.0 and a median of 25.5 CMS per patient (range of 4.8 to 85.9). There were zero CMS at baseline in Cohort 2. Radiprodil appeared generally well tolerated throughout Part A and B of the study to date. The treatment-emergent adverse events (TEAEs) most commonly observed (i.e., in three or more patients) were those associated with infections or underlying disease symptoms including pyrexia, diarrhea, respiratory tract infection, abnormal behavior, agitation, cough, dystonia, fatigue, and gastroenteritis. There were no deaths in the study. Three patients experienced a serious adverse event (one patient each with obstructive bronchitis, viral pneumonia, or adenovirus infection). None were considered related to treatment with radiprodil and none met study stopping rule criteria. During Part A of the study, patients treated with radiprodil showed a median reduction of 86% in seizure frequency versus baseline, which was a key secondary endpoint in the trial. During this same period, 71% of patients had a greater than 50% reduction in CMS, with 43% seeing a greater than 90% reduction and one patient being seizure free. Clinicians and caregivers also generally assessed patients as improved clinically over the course of the study. "We believe the findings from the Honeycomb study in gain-of-function patients with treatment resistant symptoms provide strong rationale to progress this promising program into Phase 3 development as quickly as possible," said Bruce Leuchter, MD, President and Chief Executive Officer at Neurvati Neurosciences and GRIN Therapeutics. "I am proud of the progress we have made to address the profound unmet need in GRIN-related neurodevelopmental disorder since we launched the company three years ago with an investment from Blackstone Life Sciences. These compelling data represent the first major milestone in our development plans for radiprodil and will help us build new levels of momentum toward achieving our goal of bringing the first approved treatment to patients living with GRIN-related neurodevelopmental disorder." About GRIN-related neurodevelopmental disorder: GRIN-related neurodevelopmental disorder is a family of rare, genetically defined pediatric neurodevelopmental disorders caused by mutations in GRIN genes. While symptoms of GRIN-related neurodevelopmental disorder can present as early as infancy, a diagnosis is often not confirmed until age two or later when a child fails to reach developmental milestones. Individuals may experience developmental delay, intellectual disabilities, epilepsy, muscular hypotonia, movement disorders, spasticity, feeding difficulties and behavioral problems. There are currently no approved therapies for GRIN-related neurodevelopmental disorder. About Radiprodil: Radiprodil is an investigational, selective and potent negative allosteric modulator of the N-methyl-D-aspartate receptor subtype 2B (NR2B or GluN2B). In nonclinical studies, radiprodil has been shown to potently and selectively modulate the N-methyl-D-aspartate (NMDA) receptor subtype 2B (NR2B or GluN2B). Radiprodil has also demonstrated an antiseizure effect in a number of in vitro and in vivo preclinical seizure and epilepsy models and specifically in models characterized by an enhanced GluN2B-NMDA transmission, which can occur with gain-of-function (GoF) mutations in GRIN-related disorder. About GRIN Therapeutics: GRIN Therapeutics is dedicated to the research and development of precision therapeutics for pediatric neurodevelopmental disorders with the goal of bringing hope to patients and caregivers. Working to develop the investigational product radiprodil as a novel therapy for patients with neurodevelopmental disorders, the company has two ongoing clinical trials to evaluate radiprodil for the potential treatment of GRIN-related neurodevelopmental disorder and other neurological conditions including tuberous sclerosis complex (TSC) and focal cortical dysplasia (FCD) type II. GRIN Therapeutics is an affiliate of Neurvati Neurosciences, a portfolio company of Blackstone Life Sciences (BXLS). For more information, please visit About Neurvati Neurosciences Neurvati Neurosciences, a portfolio company of Blackstone Life Sciences, identifies and advances the development of high-potential drug candidates across the neuroscience landscape. Neurvati employs a collaborative model that establishes fit-for-purpose affiliate companies, aligning dedicated resources with long-term strategic capital to catalyze innovative treatment options in areas of unmet need. Neurvati's team of experienced operators and drug developers seeks opportunities to challenge current treatment paradigms and make a difference for patients suffering from a wide range of neurological and psychiatric disorders. For more information, please visit . About Blackstone Life Sciences Blackstone Life Sciences is an industry-leading private investment platform with capabilities to invest across the life cycle of companies and products within key life science sectors. By combining scale investments and hands-on operational leadership, Blackstone Life Sciences helps bring to market promising new medicines and medical technologies that improve patients' lives and currently has more than $9 billion in assets under management. Corporate Contact: Elliott Ruiz +1 201.674.5417 [email protected] SOURCE GRIN Therapeutics Inc.