DAAO

- Neurocrine Obtains Exclusive Worldwide Development and Commercialization Rights Excluding Japan and Converts to Royalty-Bearing License for Osavampator - Takeda Reacquires Rights to Osavampator in Japan SAN DIEGO, Jan. 27, 2025 /PRNewswire/ -- Neurocrine Biosciences, Inc. (Nasdaq: NBIX) today announced it has amended its agreement with Takeda to develop and commercialize osavampator (NBI-1065845/TAK-653). Under the amended agreement, Neurocrine will obtain exclusive rights for all indications to develop and commercialize osavampator, a potential first-in-class AMPA positive allosteric modulator in development for patients with inadequate response to treatment of major depressive disorder (MDD) in all territories worldwide except Japan, where Takeda will reacquire exclusive rights. Under the terms of the updated agreement, each company is responsible for development costs in their respective region, and both companies are eligible to receive royalty payments. "This streamlined collaboration structure allows Neurocrine to focus on bringing this important medicine to patients as quickly as possible," said Kyle Gano, Ph.D., Chief Executive Officer at Neurocrine Biosciences. "With the recent successful completion of our End-of-Phase 2 meeting with FDA for osavampator, we look forward to beginning the Phase 3 program in the first half of this year." "With its long-standing expertise developing therapies for serious psychiatric disorders, Neurocrine is the ideal partner to develop osavampator," said Sarah Sheikh, M.Sc., B.M., B.Ch, MRCP, Head, Neuroscience Therapeutic Area Unit and Head, Global Development at Takeda. "As it continues to progress through clinical development, osavampator has the potential to add a meaningful new treatment option for patients with MDD." About the Collaboration with Takeda In 2020, Neurocrine Biosciences and Takeda entered into a strategic collaboration to develop and commercialize compounds in depression and schizophrenia, including an exclusive license to both osavampator and NBI-1070770, which are being studied for the treatment of major depressive disorder, as well as a preclinical GPR139 antagonist development program. About Osavampator Osavampator is a potential first-in-class, investigational alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) positive allosteric modulator (PAM) in development for patients with MDD who have not benefited from treatment with at least one antidepressant in their current episode of depression. In April 2024, Neurocrine announced positive topline data for its Phase 2 SAVITRI™ study in adult subjects with MDD. Neurocrine plans to initiate a Phase 3 program in the first half of this year. About Major Depressive Disorder Major depressive disorder (MDD) is a serious disorder characterized by a persistently depressed mood, loss of interest, poor concentration, and decreased energy, among other symptoms. According to the World Health Organization, MDD is one of the leading causes of disability, is a serious condition that presents an increased risk of suicide and self-harm, and is associated with increased all-cause mortality rates. More than 21 million people in the U.S. live with MDD and it is estimated that roughly a third of those do not respond to available antidepressants. About Neurocrine Biosciences Neurocrine Biosciences is a leading neuroscience-focused, biopharmaceutical company with a simple purpose: to relieve suffering for people with great needs. 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, classic congenital adrenal hyperplasia, 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. SAVITRI is a trademark 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 benefits to be derived from transactions with Takeda Pharmaceutical Company Limited; statements regarding the clinical results from, and our future development plans with respect to, osavampator, as well as the therapeutic potential and clinical benefits or safety profile of osavampator. Among the factors that could cause actual results to differ materially from those indicated in the forward-looking statements include: 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; risks that the benefits of the agreements with Takeda may never be realized; 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 September 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. SOURCE Neurocrine Biosciences, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

William Blair analysts said they “viewed luvadaxistat development as high risk.” Neurocrine Biosciences’ schizophrenia program pivot has failed. The biotech was unable to replicate the cognition signal it saw in an earlier midphase study, prompting it to stop development of luvadaxistat.San Diego-based Neurocrine in-licensed the DAAO inhibitor luvadaxistat and other R&D programs from Takeda for $120 million upfront in 2020. The next year, a phase 2 trial of luvadaxistat missed its primary endpoint. However, while the candidate failed to improve schizophrenia symptoms on the PANSS scale, Neurocrine did track a significant improvement on secondary endpoints that looked at cognition.The secondary endpoint wins persuaded Neurocrine to run a second phase 2 trial that largely replicated the design of the earlier study. The key difference was the use of the Brief Assessment of Cognition in Schizophrenia as the primary endpoint. Neurocrine included another cognition scale as a secondary goal.This time around, the biotech failed to replicate the cognitive data seen in the earlier trial. Neurocrine said the failure was partly caused by “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.” Rather than try to address those issues in a third trial, the biotech has decided to stop development of the drug candidate and focus its resources on other assets. Specifically, Neurocrine plans to pump the money into phase 3 studies of NBI-1117568 for schizophrenia and NBI-1065845 for major depressive disorder.Neurocrine’s share price fell 2% to below $119 in premarket trading, a muted reaction that likely reflects expectations for the program. William Blair analysts said they “viewed luvadaxistat development as high risk” in a note published in response to the failed trial. Neurocrine was open about the risks in the run-up to the readout, too.“Cognitive impairment associated with schizophrenia has been a very, very challenging area. It's about as high risk as you could get, in my view, and there's not a lot known about clinical development in this space because there's such a few number of companies that have worked here,” Kyle Gano, Ph.D., chief business development and strategy officer at Neurocrine, said at a Wells Fargo event last week.There are no FDA-approved treatments for cognitive impairment associated with schizophrenia. Biogen, Roche and Pfizer have studied candidates in the setting but no longer have any active trials. Recognify Life Sciences, an atai Life Sciences company, is running a phase 2 trial that is scheduled to end this year, according to ClinicalTrials.gov.

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.