DAAO

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.

INGREZZA® (valbenazine) Second Quarter Net Product Sales of $580 Million Representing 32% Year-Over-Year Growth INGREZZA ® (valbenazine) 2024 Net Product Sales Guidance Raised to $2.25 - $2.3 Billion Top-Line Phase 2 Data Readouts for NBI-'568 and Luvadaxistat Remain On Track in Q3 SAN DIEGO, Aug. 1, 2024 /PRNewswire/ -- Neurocrine Biosciences, Inc. (Nasdaq: NBIX) today announced its financial results for the second quarter ended June 30, 2024 and provided an update on its 2024 financial guidance. "At Neurocrine, we are energized by the tremendous opportunity we see to help many more patients, and we are encouraged by our recent progress, including INGREZZA's continued success in treating tardive dyskinesia and Huntington's disease chorea and the FDA's decision to grant Priority Review for crinecerfont to treat congenital adrenal hyperplasia," said Kevin Gorman, Ph.D., Chief Executive Officer of Neurocrine Biosciences. "We are in the process of building our endocrinology team and expanding the INGREZZA salesforce, positioning our company for continued strong growth in the years ahead." Kevin Gorman added, "As I look ahead to my planned retirement in October, I have never been more confident in Neurocrine's future. I am incredibly proud of all that we have achieved together and excited to see what this team will continue to accomplish for patients under Kyle Gano's leadership." Financial Highlights INGREZZA Net Product Sales Highlights INGREZZA second quarter 2024 net product sales were $580 million and grew 32% compared to the second quarter 2023 Year-over-year growth driven by strong underlying patient demand and improvement in gross-to-net dynamics Other Key Financial Highlights Differences in second quarter 2024 GAAP and Non-GAAP operating expenses compared with second quarter 2023 were driven by: Increased R&D expense in support of an expanded and advancing clinical portfolio including investments in muscarinic compounds, gene therapy programs and second generation VMAT2 inhibitors. R&D expense for the second quarter 2024 includes $27 million for development milestones achieved under our collaborations with Nxera Pharma UK Limited (Nxera, formerly known as Sosei Heptares), Takeda Pharmaceutical Company Limited (Takeda) and Voyager Therapeutics, Inc. (Voyager) Increased SG&A expense includes incremental investment in crinecerfont-related headcount, crinecerfont-related pre-launch activities, and continued investment in INGREZZA. GAAP SG&A expense also includes impairment charges of $14 million associated with leased office space that has been vacated as we continue to occupy our new campus facility Second quarter 2024 GAAP net income and earnings per share were $65 million and $0.63, respectively, compared with $96 million and $0.95, respectively, for second quarter 2023 Second quarter 2024 Non-GAAP net income and earnings per share were $169 million and $1.63, respectively, compared with $126 million and $1.25, respectively, for second quarter 2023 Differences in second quarter 2024 GAAP and Non-GAAP net income compared with second quarter 2023 driven by: Higher INGREZZA net sales and improved operating margin Second quarter 2024 includes $50 million charge associated with the settlement of convertible senior notes conversions (Non-GAAP adjustment) Second quarter 2024 includes $20 million loss from changes in fair value of equity security investments compared to $37 million gain the second quarter 2023 (Non-GAAP adjustment) Second quarter 2024 includes $27 million of development milestones expense achieved under collaborations Second quarter 2024 includes $14 million leased office space impairment charge (Non-GAAP adjustment) At June 30, 2024, the Company had cash, cash equivalents and marketable securities totaling approximately $1.7 billion which reflects the $309 million payment to fully retire our convertible senior notes A reconciliation of GAAP to Non-GAAP financial results can be found in Table 3 and Table 4 at the end of this news release. Recent Developments Announced Kevin Gorman, Ph.D., will retire as Chief Executive Officer on October 11, 2024. Kyle Gano, Ph.D., currently Neurocrine's Chief Business Development and Strategy Officer, will succeed him in the CEO role. Dr. Gano will also join the Company's Board of Directors at that time, and Dr. Gorman will continue to serve on the Company's Board. Announced positive topline data for the Phase 2 SAVITRI™ study. This randomized, double-blind, placebo-controlled dose-finding study assessed the efficacy and safety of NBI-1065845 in adult subjects with major depressive disorder (MDD). NBI-1065845 is an investigational alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) positive allosteric modulator (PAM) in development as a potential treatment for patients with MDD who have not benefited from treatment with at least one antidepressant in their current episode of depression. Announced FDA accepted New Drug Applications (NDAs) and granted Priority Review for crinecerfont for adult and pediatric patients with congenital adrenal hyperplasia (CAH). The agency set Prescription Drug User Fee (PDUFA) target actions dates of December 29, 2024 for the capsule formulation and December 30, 2024 for the oral solution formulation. At the Endocrine Society Annual Meeting (ENDO 2024), presented new Phase 3 clinical study data from the CAHtalyst™ registrational studies of crinecerfont in pediatric and adult patients with classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. In parallel, announced that the primary study results from the CAHtalyst™ registrational studies of crinecerfont in pediatric and adult patients with classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency have been published in The New England Journal of Medicine. Initiated Phase 2 study of NBI-1070770 in adults with major depressive disorder. NBI-1070770 is a novel, selective and orally active, negative allosteric modulator (NAM) of the NR2B subunit-containing N-methyl-D-aspartate (NMDA NR2B) receptor. Initiated Phase 1 study of NBI-1117567 in healthy adult participants. NBI-1117567 is an investigational, oral, M1/M4 (M1 preferring) selective muscarinic agonist for the potential treatment of neurological and neuropsychiatric conditions. Initiated Phase 1 study of NBI-1076968 in healthy adult participants. NBI-1076968 is an investigational, oral, M4 subtype-selective muscarinic antagonist for the potential treatment of movement disorders. Received notification from the Centers for Medicare and Medicaid Services that INGREZZA qualified for the Specified Small Manufacturer Exception pertaining to the Part D redesign of the Inflation Reduction Act. Settled the convertible senior notes due May 15, 2024 in full in cash upon maturity. Announced planned expansion of the INGREZZA psychiatry and long-term care sales teams to better serve patients by accelerating the number of people who are diagnosed and treated for tardive dyskinesia and chorea associated with Huntington's disease. Launched new sprinkle formulation of INGREZZA® (valbenazine) capsules for the treatment of adults with tardive dyskinesia and chorea associated with Huntington's disease. Raised 2024 Net Sales Guidance and Updated Expense Guidance 2024 Pipeline Milestones and Key Activities Key: AMPA = alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid; CFR1 = Corticotropin-Releasing Factor Type 1; M4 = M4 Muscarinic Receptor; DAAO = d-amino acid oxidase; NMDA NR2B NAM = n-methyl-d-aspartate Receptor Subtype 2B Negative Allosteric Modulator; VMAT2 = Vesicular Monoamine Transporter 2; M1 = M1 Muscarinic Receptor Neurocrine Biosciences Partners: * Partnered with Takeda Pharmaceutical Company Limited; ** In-Licensed from Nxera Pharma UK Limited (formerly Sosei Heptares) Conference Call and Webcast Today at 8:00 AM Eastern Time Neurocrine Biosciences will hold a live conference call and webcast today at 8:00 a.m. Eastern Time (5:00 a.m. Pacific Time). Participants can access the live conference call by dialing 800-445-7795 (US) or 785-424-1699 (International) using the conference ID: NBIX. The webcast and accompanying slides can also be accessed at approximately 8:00 a.m. Eastern Time on Neurocrine Biosciences' website under Investors at . A replay of the webcast will be available on the website approximately one hour after the conclusion of the event and will be archived for approximately one month. About Neurocrine Biosciences Neurocrine Biosciences is a 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) NEUROCRINE BIOSCIENCES, NEUROCRINE and YOU DESERVE BRAVE SCIENCE are registered trademarks of Neurocrine Biosciences, Inc. The Neurocrine logo is a trademark of Neurocrine Biosciences, Inc. Non-GAAP Financial Measures In addition to the financial results and financial guidance that are provided in accordance with accounting principles generally accepted in the United States (GAAP), this press release also contains the following Non-GAAP financial measures: Non-GAAP R&D expense, Non-GAAP SG&A expense, and Non-GAAP net income and net income per share. When preparing the Non-GAAP financial results and guidance, the Company excludes certain GAAP items that management does not consider to be normal, including recurring cash operating expenses that might not meet the definition of unusual or non-recurring items. In particular, these Non-GAAP financial measures exclude: non-cash stock-based compensation expense, charges associated with convertible senior notes, impairment charges associated with leased properties, non-cash amortization expense related to acquired intangible assets, acquisition and integration costs, changes in fair value of equity security investments, changes in foreign currency exchange rates and certain adjustments to income tax expense. These Non-GAAP financial measures are provided as a complement to results provided in accordance with GAAP as management believes these Non-GAAP financial measures help indicate underlying trends in the Company's business, are important in comparing current results with prior period results and provide additional information regarding the Company's financial position. Management also uses these Non-GAAP financial measures to establish budgets and operational goals that are communicated internally and externally and to manage the Company's business and evaluate its performance. The Company provides guidance regarding combined R&D and SG&A expenses on both a GAAP and a Non-GAAP basis. A reconciliation of these GAAP financial results to Non-GAAP financial results is included in the attached financial information. 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 our products and product candidates; the value our products and/or our product candidates may bring to patients; the continued success of INGREZZA; our financial and operating performance, including our future revenues, expenses, or profits; our collaborative partnerships; expected future clinical and regulatory milestones; and the timing of the initiation and/or completion of our clinical, regulatory, and other development activities and those of our collaboration partners. Among the factors that could cause actual results to differ materially from those indicated in the forward-looking statements are: our future financial and operating performance; risks and uncertainties associated with the commercialization of INGREZZA; risks that the crinecerfont New Drug Applications (NDAs) may not obtain regulatory approval, such approval may be delayed, or may not receive the benefits associated with priority review; risks related to the development of our product candidates; 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 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; 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 government and third-party regulatory and/or policy efforts which may, among other things, impose sales and pharmaceutical pricing controls on our products or limit coverage and/or reimbursement for our products; risks associated with competition from other therapies or products, including potential generic entrants for our products; and other risks described in our periodic reports filed with the SEC, including our 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 as required by law. SOURCE Neurocrine Biosciences, Inc.