Valbenazine Tosylate

INGREZZA showed a nearly two-fold higher VMAT2 occupancy, consistent with greater potency when compared to AUSTEDO XR (deutetrabenazine) after a single dose of each treatment VMAT2 occupancy is a key measurement thought to be associated with drug response in involuntary movement disorders, including tardive dyskinesia and Huntington's disease chorea SAN DIEGO, Jan. 15, 2026 /PRNewswire/ -- Neurocrine Biosciences, Inc. (Nasdaq: NBIX) today announced the presentation of the first head-to-head data comparing vesicular monoamine transporter 2 (VMAT2) target occupancy between INGREZZA® (valbenazine) capsules and AUSTEDO XR (deutetrabenazine) at therapeutic doses. Results from the study confirmed that both compounds engage VMAT2; however, INGREZZA demonstrated significantly higher VMAT2 target occupancy and greater potency. Findings were presented at the American College of Neuropsychopharmacology 64th Annual Meeting taking place January 12-15 in the Bahamas. VMAT2 inhibition is an established target for treatment of hyperkinetic movement disorders, such as tardive dyskinesia (TD) and Huntington's disease (HD) chorea. VMAT2 target occupancy (TO) is a key measurement thought to be associated with the level of drug response in these conditions. Higher VMAT2 occupancy indicates greater engagement of the target, and inhibition of VMAT2 lowers excessive dopamine transmission associated with involuntary movements. "In this head-to-head assessment, INGREZZA demonstrated approximately two-fold higher target occupancy compared with AUSTEDO XR at therapeutic doses," said Sanjay Keswani, M.D., Chief Medical Officer, Neurocrine Biosciences. "The significantly higher VMAT2 occupancy observed with INGREZZA adds to the already established differences between VMAT2 inhibitors in pharmacologic and clinical profiles. The high occupancy of INGREZZA may contribute to the robust early and sustained clinical efficacy consistently demonstrated in multiple tardive dyskinesia and Huntington's disease chorea clinical trials." The study used positron emission tomography (PET) imaging to evaluate VMAT2 TO following single doses of either INGREZZA (40 mg or 80 mg) or AUSTEDO XR (24 mg or 48 mg) in eight participants, each completing four PET visits. Using a linear mixed-effects model, the primary TO analysis demonstrated a least squares mean VMAT2 occupancy of approximately 76.5% for INGREZZA compared with approximately 38.3% for AUSTEDO XR at therapeutic doses. Pharmacokinetic exposure modeling and calculated half-maximal effective concentration (EC50) values enabled estimates of steady-state TO with superior VMAT2 engagement at therapeutic doses of INGREZZA compared to AUSTEDO XR. Findings are depicted in the table below: VMAT2 Inhibitor Dose (mg) Estimated Steady-State VMAT2 Occupancy INGREZZA 40 83 % 80 92 % AUSTEDO XR 24 54 % 48 70 % These data are consistent with our integrated understanding of the TO of INGREZZA and drug exposure concentrations observed from INGREZZA in pivotal clinical trials.1,2 The superior target engagement observed with INGREZZA may be related to its single high affinity metabolite, compared with AUSTEDO XR, which generates multiple metabolites, including those with lower VMAT2 affinity. All doses of INGREZZA and AUSTEDO XR were generally well tolerated and consistent with the known safety profile of each compound. Additional presentations at the 2026 American College of Neuropsychopharmacology Annual Meeting: Once-Daily Valbenazine Improves Patient-Reported Quality of Life in Patients From KINECT-PRO™ Who Met a Remission Threshold for Tardive Dyskinesia Potential Change in Disease Burden with Valbenazine in Adults with Huntington's Disease: Post Hoc Analysis of Cognitive- and Emotional-Related HD-HI Items in the KINECT®-HD Trial Osavampator (NBI-1065845/TAK-653) Demonstrates Statistically Significant and Clinically Meaningful Improvements in Depression Severity and is Well Tolerated in Adults with Major Depressive Disorder: Phase 2 SAVITRI Results About Tardive Dyskinesia Tardive dyskinesia (TD) is a movement disorder that is characterized by uncontrolled, abnormal and repetitive movements of the face, torso and/or other body parts, which may be disruptive and negatively impact patients. The condition is associated with taking certain kinds of mental health medicines (antipsychotics) that help control dopamine receptors in the brain. Taking antipsychotics commonly prescribed to treat mental illnesses such as major depressive disorder, bipolar disorder, schizophrenia and schizoaffective disorder and other prescription medicines (metoclopramide and prochlorperazine) used to treat gastrointestinal disorders are associated with TD. In patients with TD, these treatments are thought to result in irregular dopamine signaling in a region of the brain that controls movement. The symptoms of TD can be mild to severe and are often persistent and irreversible. TD is estimated to affect at least 800,000 adults in the U.S. About Chorea Associated with Huntington's Disease Huntington's disease (HD) is a hereditary progressive neurodegenerative disorder in which the loss of certain neurons within the brain causes motor, cognitive and psychiatric symptoms. Symptoms generally appear between the ages of 30 and 50 years and worsen over a 10- to 25-year period. Most people with HD experience chorea, an abnormal involuntary movement disorder, characterized by irregular and unpredictable movements. Chorea can affect various body parts and interfere with motor coordination, gait, swallowing and speech. HD is estimated to affect approximately 41,000 adults in the U.S., with more than 200,000 at risk of inheriting the disease. About INGREZZA® (valbenazine) Capsules and INGREZZA® SPRINKLE (valbenazine) Capsules INGREZZA is a selective vesicular monoamine transporter 2 (VMAT2) inhibitor approved by the U.S. Food and Drug Administration for the treatment of adults with tardive dyskinesia and the treatment of chorea associated with Huntington's disease (HD). Only INGREZZA offers a therapeutic dose from day one with no required titration. INGREZZA, developed by Neurocrine Biosciences, selectively inhibits VMAT2 with no appreciable binding affinity for VMAT1, dopaminergic (including D2), serotonergic, adrenergic, histaminergic or muscarinic receptors. While the specific way INGREZZA works to treat TD and HD chorea is not fully understood, INGREZZA is unique in that it selectively and specifically targets VMAT2 to inhibit the release of dopamine, a chemical in the brain that helps control movement. INGREZZA is believed to reduce extra dopamine signaling, which may lead to fewer uncontrollable movements. INGREZZA is studied across the widest range of patients. It is always one capsule, once daily and can be taken together with most stable mental health regimens such as antipsychotics or antidepressants. Only INGREZZA offers the benefit of a sprinkle formulation, INGREZZA SPRINKLE, for those who experience dysphagia, have difficulty swallowing or prefer not to swallow a pill. INGREZZA and INGREZZA SPRINKLE dosages approved for use are 40 mg, 60 mg and 80 mg capsules. Important Information Approved Uses INGREZZA® (valbenazine) capsules or INGREZZA® SPRINKLE (valbenazine) capsules are prescription medicines used to treat adults with: movements in the face, tongue, or other body parts that cannot be controlled (tardive dyskinesia). involuntary movements (chorea) of Huntington's disease. INGREZZA or INGREZZA SPRINKLE do not cure the cause of involuntary movements, and do not treat other symptoms of Huntington's disease, such as problems with thinking or emotions. It is not known if INGREZZA or INGREZZA SPRINKLE is safe and effective in children. IMPORTANT SAFETY INFORMATION INGREZZA or INGREZZA SPRINKLE can cause serious side effects in people with Huntington's disease, including: depression, suicidal thoughts, or suicidal actions. Tell your healthcare provider before you start taking INGREZZA or INGREZZA SPRINKLE if you have Huntington's disease and are depressed (have untreated depression or depression that is not well controlled by medicine) or have suicidal thoughts. Pay close attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings. This is especially important when INGREZZA or INGREZZA SPRINKLE is started and when the dose is changed. Call your healthcare provider right away if you become depressed, have unusual changes in mood or behavior, or have thoughts of hurting yourself. Do not take INGREZZA or INGREZZA SPRINKLE if you: are allergic to valbenazine, or any of the ingredients in INGREZZA or INGREZZA SPRINKLE. INGREZZA or INGREZZA SPRINKLE can cause serious side effects, including: Allergic reactions. Allergic reactions, including an allergic reaction that causes sudden swelling called angioedema, can happen after taking the first dose or after many doses of INGREZZA or INGREZZA SPRINKLE. Signs and symptoms of allergic reactions and angioedema include: trouble breathing or shortness of breath, swelling of your face, lips, eyelids, tongue, or throat, or other areas of your skin, trouble with swallowing, or rash, including raised, itchy red areas on your skin (hives). Swelling in the throat can be life-threatening and can lead to death. Stop taking INGREZZA or INGREZZA SPRINKLE and go to the nearest emergency room right away if you develop these signs and symptoms of allergic reactions and angioedema. Sleepiness and tiredness that could cause slow reaction times (somnolence and sedation). Do not drive a car or operate dangerous machinery until you know how INGREZZA or INGREZZA SPRINKLE affects you. Drinking alcohol and taking other medicines may also cause sleepiness during treatment with INGREZZA or INGREZZA SPRINKLE. Heart rhythm problems (QT prolongation). INGREZZA or INGREZZA SPRINKLE may cause a heart rhythm problem known as QT prolongation. You have a higher chance of getting QT prolongation if you also take certain other medicines during treatment with INGREZZA or INGREZZA SPRINKLE. Tell your healthcare provider right away if you develop any signs or symptoms of QT prolongation, including: fast, slow, or irregular heartbeat (heart palpitations), shortness of breath, dizziness or lightheadedness, or fainting or feeling like you are going to faint. Neuroleptic Malignant Syndrome (NMS). NMS is a serious condition that can lead to death. Call a healthcare provider right away or go to the nearest emergency room if you develop these symptoms and they do not have another obvious cause: high fever, stiff muscles, problems thinking, irregular pulse or blood pressure, increased sweating, or very fast or uneven heartbeat. Parkinson-like symptoms. Symptoms include: body stiffness, drooling, trouble moving or walking, trouble keeping your balance, shaking (tremors), or falls. Before taking INGREZZA or INGREZZA SPRINKLE, tell your healthcare provider about all of your medical conditions including if you: have liver or heart problems, are pregnant or plan to become pregnant, or are breastfeeding or plan to breastfeed. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Make sure you tell all of your healthcare providers that you are taking INGREZZA or INGREZZA SPRINKLE. Taking INGREZZA or INGREZZA SPRINKLE with certain other medicines may cause serious side effects. Especially tell your healthcare provider if you: take digoxin or take or have taken a monoamine oxidase inhibitor (MAOI) medicine. You should not take INGREZZA or INGREZZA SPRINKLE if you are taking, or have stopped taking, a MAOI within the last 14 days. The most common side effects of INGREZZA or INGREZZA SPRINKLE in people with tardive dyskinesia are sleepiness and tiredness. The most common side effects of INGREZZA or INGREZZA SPRINKLE in people with chorea associated with Huntington's disease include sleepiness and tiredness, raised itchy red areas on your skin (hives), rash, and trouble getting to sleep or staying asleep. These are not all of the possible side effects of INGREZZA or INGREZZA SPRINKLE. Call your doctor for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit MedWatch at www.fda.gov/medwatch or call 1-800-FDA-1088. Dosage Forms and Strengths: INGREZZA and INGREZZA SPRINKLE are available in 40 mg, 60 mg, and 80 mg capsules. Please see full Prescribing Information, including Boxed Warning, and Medication Guide. About Neurocrine Biosciences, Inc. Neurocrine Biosciences is a leading 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, endocrine, psychiatric and immunological 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, Facebook and YouTube. (*in collaboration with AbbVie) The NEUROCRINE BIOSCIENCES Logo, NEUROCRINE, YOU DESERVE BRAVE SCIENCE, INGREZZA and KINECT are registered trademarks of Neurocrine Biosciences, Inc. KINECT-PRO and SAVITRI are trademarks of Neurocrine Biosciences, Inc. Third-party trademarks are property of their respective owners. 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 regarding the potential benefits to be derived from INGREZZA, the interpretation and potential relevance of the data described in this press release, including expectations as to how such data may relate to the therapeutic effects and clinical efficacy of INGREZZA, and the value INGREZZA may bring to patients. Factors that could cause actual results to differ materially from those stated or implied in the forward-looking statements include, but are not limited to, the following: risks and uncertainties as to whether the data described in this press release will be replicated in additional studies or will be predictive of efficacy or other clinical outcomes in subsequent clinical studies or real-world use of INGREZZA; risks and uncertainties associated with Neurocrine Biosciences' business and finances in general, as well as risks and uncertainties associated with the commercialization of INGREZZA; whether INGREZZA receives adequate reimbursement from third-party payors; risks and uncertainties relating to competitive products and technological changes that may limit demand for INGREZZA; risks associated with the Company's dependence on third parties for development and manufacturing activities related to INGREZZA, and the ability of the Company to manage these third parties; risks that additional regulatory submissions for INGREZZA or other product candidates may not occur or be submitted in a timely manner; risks that the FDA or other regulatory authorities may make adverse decisions regarding INGREZZA; risks that post-approval INGREZZA commitments or requirements may be delayed; risks that INGREZZA 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; 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, 2025. Neurocrine Biosciences disclaims any obligation to update the statements contained in this press release after the date hereof other than required by law. REFERENCES © 2026 Neurocrine Biosciences, Inc. All Rights Reserved. CAP-VBZ-US-0089 01/2026 View original content to download multimedia:https://www.prnewswire.com/news-releases/neurocrine-biosciences-presents-head-to-head-ingrezza-valbenazine-capsules-data-demonstrating-higher-vmat2-target-occupancy-compared-to-austedo-xr-302661800.html SOURCE Neurocrine Biosciences, Inc. Media: Aimee White, 1-858-354-7865, media@neurocrine.com ; Investors: Todd Tushla , 1-858-617-7143 , ir@neurocrine.com

There are currently no approved therapies to treat uncontrolled movements in cerebral palsy. Just days after an upbeat R&D event, Neurocrine Biosciences has found itself having to report a phase 3 failure.The company’s Ingrezza (valbenazine), approved to treat certain uncontrolled movement conditions, failed to make a significant difference in a phase 3 trial for patients with dyskinesia due to cerebral palsy (CP), Neurocrine announced Monday.Ingrezza didn’t outperform placebo on improving involuntary, jerky movements of the body after 14 weeks of treatment, causing the phase 3 trial to miss its primary endpoint. The study, dubbed Kinect-DCP, also did not meet key secondary endpoints, according to Neurocrine.Dyskinetic CP is a subtype of CP, which is a nonprogressive neurological disorder that affects body movement and posture. Dyskinetic CP accounts for about 15% of all CP cases and is marked by various involuntary movements, including dystonia, chorea and athetosis.Ingrezza is a vesicular monoamine transporter 2 inhibitor indicated for two other neurological disorders with uncontrollable movements: tardive dyskinesia and chorea associated with Huntington’s disease. Currently, there are no approved therapies to treat uncontrolled movements in CP. While disappointing, the miss in dyskinetic CP has little impact on Neurocrine’s business within analysts’ expectations. In a Dec. 16 note, Jefferies analysts figured Ingrezza only had a 10% chance at success in dyskinetic CP. William Blair analysts labeled the fail’s effect on their valuation of Neurocrine as “minimal.”The value of the company is currently driven by commercialization of Ingrezza and the launch progress of newly FDA-approved Crenessity in a genetic condition that affects the adrenal glands. In the third quarter, Ingrezza sales increased by 12% year over year to reach $687 million, while Crenessity generated $98 million following its FDA nod in December 2024.On the pipeline side, the company’s focus is on two late-stage candidates, osavampator and direclidine. Neurocrine advanced osavampator, a potential first-in-class AMPA modulator, into phase 3 trials in major depressive disorder at the beginning of the year, with an initial readout expected in 2027. Direclidine, an M4 agonist, is also slated for a phase 3 readout in 2027 for schizophrenia.The company is developing two next-generation VMAT2 inhibitors, led by NBI-1065890, which will enter phase 2 soon in tardive dyskinesia, according to Neurocrine’s R&D day update Dec. 16.Neurocrine is also entering the obesity ring, unveiling at the R&D event a CRF2 agonist set to enter the clinic in the first half of 2026. The company plans to combine the drug, coded NBIP-’2118 with its own “triple G” agonist, as both a co-formulation and in a single-molecule conjugate form.