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Neurocrine Biosciences (Nasdaq: NBIX) Q3 2025 Earnings Presentation October 28 , 2025 Advancing Life -Changing Discoveries in Neuroscience
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2 In addition to historical facts, this presentation 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; successfully launching CRENESSITY; our financialand 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. 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 associated with Neurocrine Biosciences’ business and finances in general; risks and uncertainties associated with the commercialization of INGREZZA and CRENESSITY; 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 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 Securities and Exchange Commission, including our 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 presentation after the date hereof other than as requiredby law. 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 presentation 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, vacated legacy campus facility costs, net of sublease income, non-cash amortization expense related to acquired intangible assets, changes in fair value of equity 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. Safe Harbor and Forward-Looking Statements
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3 In EuropeIn the U.S. and Europe Neurocrine Discovered / Developed In the U.S. Where Are We Today? Discovered and Developed Four Novel FDA-Approved Therapies Deep Expertise in Neuroscience Drug Development Fully-Integrated Organization with R&D and Commercial Capabilities Growing Blockbuster Commercial Product in INGREZZA with Strong IP Future Blockbuster Opportunity with CRENESSITY Industry-Leading Portfolio of Muscarinic Compounds Strong Financial Profile That Supports Sustainable Innovation Across our R&D Engine and Pipeline * ‡ ‡ Building a Leading Neuroscience-Focused Company * Mitsubishi Tanabe Pharma Corporation (MTPC) has commercialization rights in Japan and other select Asian markets ‡ AbbVie has global commercialization rights ‡‡ Eton Pharmaceucticals, Inc. has U.S. commercialization rights ‡‡
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4 Well-Positioned for Sustained & Long-Term Growth *Products commercialized by Neurocrine Biosciences, Inc. in the United States of America. • Neurology • Neuroendocrinology • Neuropsychiatry • Neuroimmunology Robust and Sustainable Pipeline Multiple Compounds in Mid- to Late-Stage Studies Rapidly Growing Early-Stage Portfolio TARDIVE DYSKINESIA AND HUNTINGTON’S DISEASE CHOREA COMMERCIAL* $2.50 - $2.55 Billion 2025 INGREZZA Annual Net Sales Guidance Reaffirmed ~$2.1B Cash and Investments as of 09/30/2025 • Strong Balance Sheet • Durable Cash Flows • Attractive P&L Profile RESEARCH & DEVELOPMENT STRONG FINANCIAL POSITION CLASSIC CONGENITAL ADRENAL HYPERPLASIA Therapeutic Area Diversification Well-Defined Capital Structure
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5 PROGRA M (TARG E T ) MODALIT Y THERAP E U T IC AREA INDICAT I ON PHASE 1 PHASE 2 PHASE 3 valbenazine (VMAT2 Inhibitor) Neurology Dyskinetic Cerebral Palsy osavampator (AMPA PAM) Neuropsychiatry Inadequate Response to Treatment in Major Depressive Disorder direclidine (M4 Agonist) Neuropsychiatry Schizophrenia NBI-’770 (NMDA NR2B NAM) Neuropsychiatry Major Depressive Disorder Our Pipeline Today – 12 Programs Including 1st Biologic Program NBIP-’1435 NBI-’570 (M1/M4 Agonist) Neuropsychiatry Schizophrenia-CNS Indications NBI-‘567 (M1 Agonist) Neuropsychiatry CNS Indications NBI-’569 (M4 Agonist) Neuropsychiatry CNS Indications NBI-’986 (M4 Antagonist) Neurology Movement Disorders NBI-’890 (VMAT2 Inhibitor) Neuropsychiatry CNS Indications NBI-’355 (Nav1.2/1.6 Inhibitor) Neurology Epilepsy NBI-’675 (VMAT2 Inhibitor) Neuropsychiatry CNS Indications NBIP-’1435 (CRF1 Antagonist) Neuroendocrinology Congenital Adrenal Hyperplasia Potential Areas for Development Alzheimer’s Disease • Bipolar Disorder Lewy Body Dementia • Parkinson’s Disease Schizophrenia Industry-Leading Muscarinic Pipeline Dystonia • Parkinson’s Disease Tremor VMAT2 = Vesicular Monoamine Transporter: AMPA PAM = alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid Positive Allosteric Modulator; M4 = M4 Muscarinic Receptor; NMDA NR2B NAM = n-methyl-d-aspartate Receptor Subtype 2B Negative Allosteric Modulator; M1 = M1 Muscarinic Receptor; Nav = Sodium Channel; CRF-1 = Corticotropin Releasing Factor 1 Peptide Small Molecule Modality Key
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6 ▪ Total Neurocrine Net Product Sales of $790M Represents 16% QoQ Growth and 28% YoY Growth vs. Q2 2025 and Q3 2024, Respectively ▪ INGREZZA® (valbenazine) Net Product Sales of $687M − Represents 10% QoQ Growth and 12% YoY Growth vs. Q2 2025 and Q3 2024, Respectively − Double-Digit Volume Growth Driven by Strong Patient Demand, Including Record Quarterly New and Total Prescriptions ▪ CRENESSITY® (crinecerfont) Net Product Sales of $98M Including 540 Total New Patient Enrollment Forms − Over 1,600 Classic Congenital Adrenal Hyperplasia Patients in the U.S. on Therapy Since Launch − 80% Reimbursement Coverage for Dispensed Scripts ▪ Initiated All Phase 3 Registrational Studies for: − osavampator (AMPA PAM) as an Adjunctive Therapy for the Treatment of MDD in Adults − direclidine (Selective M4 Agonist) for the Treatment of Schizophrenia ▪ Presented New osavampator Data from Phase 2 SAVITRITM Study at 38th Annual Psych Congress − Showed Statistically Significant and Clinically Meaningful Improvement in Depression Severity at Day 28 and Day 56 with Once-Daily Oral Administration of 1mg Dose 2025 Q3 Recent Highlights and Key Milestones Q3 2025 / Recent Highlights 2025 Key Milestones / Activities ▪ INGREZZA Net Sales Guidance Reaffirmed at $2.5 - $2.55 Billion − Reflects Double-Digit Volume Growth Partially Offset by Lower Net Price Due to Expanded Access ▪ In Q4, Initiate Expansion of INGREZZA and CRENESSITY Sales Teams to Maximize Commercial Momentum − Complete by End of Q1 2026 ▪ Report Top-Line Data in Q4 2025 For: − Phase 3 Study of valbenazine for Dyskinetic Cerebral Palsy − Phase 2 Study of NBI-’770 (NMDA NR2B NAM) for the Treatment of MDD ▪ Initiate Phase 2 Studies in Q4 2025 for: − direclidine for Bipolar Mania − NBI-’570 (Selective Dual M1 / M4 Agonist) for Schizophrenia ▪ Expect Phase 1 Muscarinic Agonist Results For : − NBI-’567 (M1-Preferring Agonist) − NBI-’569 (M4 –Preferring Agonist) − NBI-’570 (Dual M1 / M4 Agonist) ▪ Advance Additional Internally Developed Pre-Clinical Programs, Including Biologics, into First-in-Human Studies ▪ Host R&D Day at Neurocrine Corporate Headquarters in San Diego on December 16, 2025 with Focus on: − Neuropsychiatry Portfolio Including osavampator and Muscarinic Agonists − R&D Transformation Progress TD = Tardive Dyskinesia; AMPA PAM = alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid Positive Allosteric Modulator; MDD= Major Depressive Disorder; M4 = M4 Muscarinic Receptor; CAH = Congenital Adrenal Hyperplasia; GC = Glucocorticoid; NMDA NR2B NAM = n-methyl-d-aspartate Receptor Subtype 2B Negative Allosteric Modulator; M1 = M1 Muscarinic Receptor
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7 Financials
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8 Q3 2025 Financial Summary $ Millions, Except Non-GAAP Earnings Per Share Item Q3 2025 Q3 2024 Highlights / Comments Revenue - INGREZZA Net Product Sales - CRENESSITY Net Product Sales - Other Revenues $795 $687 $98 $10 $622 $613 - $9 Total Net Product Sales of $790M Represents 28% YoY Growth INGREZZA Sales of $687M Represents 12% YoY Growth Driven by Strong Patient Demand Including Record New Patient Starts CRENESSITY Sales of $98M Include 540 Total New Patient Enrollment Start Forms Reflecting Strong Initial Demand Non-GAAP R&D Expense $228 $180 Increase Due to Support of Expanded and Advancing Pre- Clinical and Clinical Portfolio Including Investments in Osavampator and Muscarinic Franchise Non-GAAP SG&A Expense $259 $205 Increase Due to Incremental Investment in CRENESSITY- Related Headcount / Launch Activities, and Continued Investment in INGREZZA, Including September 2024 Expansion of Psychiatry and Long-Term Care Sales Teams Non-GAAP Net Income $222 $189 Increased INGREZZA and CRENESSITY Sales Offset by Increased Investment in R&D and SG&A Non-GAAP Earnings per Share, Diluted $2.17 $1.81 Represents 20% YoY Growth Cash and Investments (Period End) $2,113 $1,872 All income statement items, except revenue, are non-GAAP financial measures; see reconciliations accompanying the presentation. All numbers except EPS rounded to the nearest million. Totals may not sum due to rounding.
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9 Year-to-Date 2025 Financial Summary $ Millions, Except Non-GAAP Earnings Per Share Item YTD 2025 YTD 2024 Highlights / Comments Revenue - INGREZZA Net Product Sales - CRENESSITY Net Product Sales - Other Revenues $2,055 $1,856 $166 $33 $1,728 $1,698 - $29 YTD 2025 Revenue Growth of 19% vs. YTD 2024 Driven by Increase in INGREZZA and CRENESSITY Sales Non-GAAP R&D Expense $691 $498 Increase Due to Incremental Investments in Expanded and Advancing Pre-Clinical and Clinical Portfolio Including Osavampator and Muscarinic Franchise Non-GAAP SG&A Expense $759 $621 Increase Due to Incremental Investment in CRENESSITY- Related Headcount and Launch Activities, and Continued Investment in INGREZZA, Including September 2024 Expansion of Psychiatry and Long-Term Care Sales Teams Non-GAAP Net Income $460 $483 Decrease Driven by Higher Pipeline and Commercial Investments Partially Offset by Increased INGREZZA and CRENESSITY Sales Non-GAAP Earnings per Share, Diluted $4.51 $4.64 Cash and Investments (Period End) $2,113 $1,872 All income statement items, except revenue, are non-GAAP financial measures; see reconciliations accompanying the presentation. All numbers except EPS rounded to the nearest million. Totals may not sum due to rounding. YTD = Q1 through Q3 for each period
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10 Reaffirmed Full Year 2025 INGREZZA Guidance and Updated Financial Guidance Item ($ Millions) 2024 Actuals 2025 Current Guidance Range Comments INGREZZA Net Product Sales1 $2,314 $2,500 - $2,550 Sales Guidance Reaffirmed Reflecting Double-Digit Volume Growth Partially Offset by Lower Net Price Due to Expanded Access GAAP R&D Expense2 $731 $1,000 - $1,020 Updated vs. Previous Guidance Range Non-GAAP R&D Expense2, 3 $662 $910 - $930 GAAP SG&A Expense4 $1,007 $1,140 - $1,160 Non-GAAP SG&A Expense3, 4 $863 $1,010 - $1,030 1. INGREZZA sales guidance reflects expected net product sales of INGREZZA in tardive dyskinesia and chorea associated with Huntington’s disease. 2. R&D guidance reflects the continued advancement of the Company’s pre-clinical and clinical portfolio including the initiation ofPhase 3 programs for osavampator in MDD and direclidine in schizophrenia. R&D guidance includes $62 million of expense for development milestones primarily in connection with collaborations with Takeda and Nxera that were achieved or deemed probable to achieve. Acquired in-process research and development expense is included in guidance once significant collaboration and licensing arrangements have been completed. 3. Non-GAAP guidance adjusted to exclude estimated non-cash stock-based compensation expense of approximately $90 million in R&D and $125 million in SG&A and vacated legacy campus facility costs. Non-cash stock-based compensation expense for performance-based equity awards is included in guidance once the predefined performance-based criteria for vesting is achieved or deemed probable to achieve. 4. SG&A guidance range reflects expense for ongoing commercial initiatives supporting INGREZZA growth and the launch of CRENESSITY.
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11 11 Our Medicines, Our Patients
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13 Substantial Impact on TD Patients and Care Partners Movement disorder caused by prolonged use of antipsychotics and anti-nausea medications * https://www.takeontd.com/ Source: IQVIA’s SMART Audit, Quarterly Data for Antipsychotic Class Uncontrollable, abnormal and repetitive movements >50% Low Self-Worth Psychiatric patients may already have difficulty gaining stability and social acceptance Isolation Loss of physical control may make patients more likely to withdraw from social situations Job Performance Patients believe TD affects their ability to perform their job of patients experience meaningful emotional, social and psychological impact*
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14 • KINECT-PRO is the First and Only Study to Specifically Evaluate and Demonstrate Patient-Reported Improvement with VMAT2 Inhibitor Treatment on TD Using Multiple Clinically Validated Scales • Patients taking INGREZZA Reported Robust and Clinically Meaningful Improvement in Physical, Social and Emotional Functioning • Improvements Were Seen as Early as Week 4 After Initial Treatment with the Lowest INGREZZA Dose and Sustained Through Week 24 • Even Patients with Milder Uncontrolled Movement Severity Were Negatively Impacted by Their TD at Baseline and Demonstrated Meaningful Improvements in TD Impact with INGREZZA Treatment KINECT-PROTM Study Demonstrated INGREZZA Capsules Improved Functionality and Quality of Life in Patients with Tardive Dyskinesia In KINECT-PRO, Improvements Were Observed Across All Severity Levels – Mild, Moderate and Severe – Following INGREZZA Treatment
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15 60 65 70 75 80 Increasing Antipsychotic Prescriptions (U.S.) 2017 2018 2019 2020 TRx (Millions) Nascent Tardive Dyskinesia Market Presents Significant Opportunity Sources: Neurocrine Biosciences Quarterly Data, IQVIA SMART VMAT2 = Vesicular Monoamine Transporter 2 3% Compound Annual Growth Rate from 2017 - 2024 20222021 2023 Source: U.S.Claims Data and 31 Global Scientific Publications; U.S. Tardive Dyskinesia Prevalence Estimates Updated Biannually; Last Update in October 2024 Nearly 9 of 10 T D P A T I E N T S A R E N O T C U R R E N T L Y T R E A T E D W I T H A V M A T 2 I N H I B I T O R L I K E I N G R E Z Z A 2024 ~800,000 people in the U.S. E S T I M A T E D T O A F F E CT
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16 INGREZZA® Approved by the FDA for the Treatment of Chorea Associated with Huntington’s Disease * TMC = Total Maximal Chorea ~90% of the 40,000 Chorea affects patients with HD in the U.S. Rare neurodegenerative disorder in which neurons within the brain break down Patients develop involuntary abnormal, abrupt or irregular movements INGREZZA Simple once-a-day treatment targeted for symptom control of chorea movements Safety profile consistent with and supported by extensive safety data in tardive dyskinesia In randomized, double-blind, placebo-controlled KINECT-HD study, treatment with valbenazine resulted in a placebo-adjusted mean reduction in the TMC* score of 3.2 units (p < 0.0001) INGREZZA makes dosing SIMPLE from the start ✓ No complex dose adjustments ✓ 1st dose is an efficacious dose ✓ ALWAYS one capsule, once daily ✓ Taken any time with or without food ✓ Can be added to most stable mental health regimens
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18 CRENESSITY Offers Potential to Change Standard of Care First New Treatment Available for Classic CAH in 70 Years ABOUT CRENESSITY ABOUT C ONGENITAL ADRENAL HYPERPLASIA • Rare and Life-long Genetic Condition that Affects ~20,000 Pediatric and Adult Patients in the U.S. • Caused by Variants of the CYP21A2 Gene Leading to a Deficiency of the Enzyme 21-hydroxylase Resulting In: ➢ Insufficient or Absent Cortisol Production ➢ Uncontrolled and High Levels of ACTH and Adrenal Androgens • Identified at or Soon After Birth • Can Lead to Life-Threatening Adrenal Crisis and Androgen Excess • For the past 70 years, Steroids Have Been the Only Option to Replace Missing Cortisol and Address Excess Androgens • Q3 Net Sales of $98M with 540 Total New Patient Enrollment Forms ➢ Reflecting Strong Initial Demand with over 1,600 Total New Patient Enrollment Forms Through Q3 ➢ ~80% Reimbursed Coverage for Dispensed Scripts ➢ Significant Level of Enthusiasm Across the Congenital Adrenal Hyperplasia Community • First Medication Approved as an Adjunct Treatment to Glucocorticoid Replacement to Control Androgens in Adult and Pediatric Patients Ages 4+ with Classic Congenital Adrenal Hyperplasia (CAH) • Supported by Data from the Largest-Ever Clinical Trial Program in Pediatric and Adults with Classic CAH
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19 Neuropsychiatry Pipeline
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20 osavampator (AMPA PAM)
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21 Inadequate Response to Treatment in Major Depressive Disorder (MDD) osavampator ~1/3 of the 16 Million+ People in the U.S. Who Live with MDD Do Not Respond to Available Antidepressants MDD Symptoms are Characterized by a Persistently Depressed Mood or Loss of Interest in Daily Activities that can Impact Normal Daily Functioning, Relationships, and Overall Quality of Life Current Treatments Range from Selective Serotonin Reuptake Inhibitors (SSRIs), Serotonin Norepinephrine Reuptake Inhibitors (SNRIs), and Antidepressants Along with Behavioral Therapy Potent First-in-Class AMPA Positive Allosteric Modulator • Oral, Once Daily Antidepressant Effects May be Mediated by Activation of AMPA and Resultant Downstream Pathways Phase 2 SAVITRI Study: • Met Primary Endpoint with Statistically Significant Reduction in MADRS Total Score at Day 28 • Met Key Secondary Endpoints, Including Statistically Significant Reduction in MADRS Total Score at Day 56 • osavampator was Generally Well-Tolerated Initiated Phase 3 Registrational Studies in MDD (See Study Design on Next Slide) • Anticipate Top-Line Data Readouts in 2027 osavampator* (AMPA PAM): All Three Phase 3 Registration Enabling Studies for the Treatment of MDD are Recruiting AMPA = alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid; MADRS = Montgomery Åsberg Depression Rating Scale * Investigational and not approved in any country Neurocrine Holds Exclusive Worldwide Development and Commercialization Rights Excluding Japan
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22 The SAVITRITM Study Evaluated The Efficacy and Safety of osavampator Compared vs. Placebo in Individuals with MDD • There is significant unmet need for novel antidepressant therapies with improved tolerability, response, and remission rates for MDD • osavampator is an investigational medication with a novel mechanism of action—AMPA PAM— for the treatment of MDD AMPA=alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; AMPA-PAM=positive allosteric modulator of the AMPA receptor; q.d.=once daily. Randomized, double-blind, placebo-controlled study conducted to evaluate osavampator, an investigational, potential first-in-class antidepressant drug with a novel MOA
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23 osavampator Demonstrated Statistically Significant and Clinically Meaningful Improvements in Depression Severity and was Well Tolerated in Adults with MDD Both doses were well tolerated, with no serious AEs or AEs of special interest reported • Both doses had an AE profile comparable to placebo • The most common AE was headache * P < 0.05. AE, adverse event; E.S.; effect size; LS, least squares; MADRS, Montgomery -Asberg Depression Rating Scale. SAVITRI enrolled adults with MDD and inadequate response (≤ 50% improvement) to 1 –5 prior oral antidepressant treatments. osavampator is investigational and not approved in any country. Primary (DAY 28) and secondary (DAY 56) efficacy endpoints met −5.0 −7.6 * * −8.0 E.S. = 0.39 −9.3 E.S. = 0.53 −11.3 E.S. = 0.33 −15.1 E.S. = 0.73 Response rates at DAY 56: Placebo 1 mg 3 mg 31.6% 56.4%* 41.5% Remission rates at DAY 56: Placebo 1 mg 3 mg 22.8% 48.7%* 31.7%
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24 osavampator* (AMPA PAM) SAVITRI TM Phase 2 Study Summary Results • Met Primary and Key Secondary Endpoints • Once-Daily, 1mg Oral Administration of osavampator Produced a Statistically Significant Change from Baseline vs. Placebo in Montgomery Åsberg Depression Rating Scale Total Score at both Day 28 (Primary) and Day 56 (Secondary) EFFICACY SAFETY AND TOLERABILITY • osavampator was Generally Well-tolerated • Most Common Adverse Events: Headache (Majority were Transient and Mild in Severity) • Adverse Event Profile for Both Doses of osavampator Were Comparable to Placebo • No Seizures, Deaths, or Serious Adverse Events • No Psychotomimetic or Dissociative Events • Discontinuation Rates Were Low * Investigational and not approved in any country -4.3 -7.5 -10 -8 -6 -4 -2 0 Least Squares Mean Change From Baseline in MADRS for Statistically Significant 1mg Dose Day 28 Day 56 P-Value = 0.0159 Effect Size = 0.53 P-Value = 0.0016 Effect Size = 0.73
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25 • Once-daily oral administration of osavampator 1 mg or 3 mg resulted in improvement in MADRS total scores at Day 28 and at Day 56 when compared vs. placebo • Treatment with osavampator 1 mg achieved a clinically meaningful and statistically significant improvement • Results of exploratory exposure–response analysis substantiate the continued evaluation of the 1 mg once-daily dosing in phase 3 studies in MDD • osavampator was well tolerated at both doses, with no serious adverse events or adverse events of special interest reported • The SAVITRI data support ongoing phase 3 studies to confirm the efficacy, safety and tolerability of osavampator MADRS=Montgomery-Asberg Depression Rating Scale * Investigational and not approved in any country SAVITRITM Study Supports Continued Evaluation of osavampator* as a Potential First-in-Class Antidepressant
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26 osavampator* Phase 3 Study Design 7654321 8 Day: -28 -21 -14 -7 0 7 14 21 28 35 42 49 56 63 70 VISIT: S C R E E N I N G / B A S E L I N E D O U B L E - B L I N D T R E A T M E N T Randomized 1:1 osavampator QD Placebo QD V I R T U A L V I R T U A L Safety Follow-Up AD, antidepressant; IR, inadequate response; MDD, major depressive disorder;QD, every day. Option to roll over into open-label, long-term safety study (MDD3028) AMPA-VEGA2 Notes: Primary Endpoint: Change in MADRS score vs. Placebo at Day 56 Adults 18 years and older with a Total HAM-D17 score ≥22 at screening and at study baseline Subjects randomized to placebo or osavampator QD during the 56-day double-blind treatment period (1:1 randomization) Simple Trial Design Testing osavampator QD vs. Placebo with 1:1 Randomization All Three Phase 3 Studies of Identical Design Have Initiated * Investigational and not approved in any country
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27 Muscarinic Agonists
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28 Muscarinic Platform Includes Multiple Clinical Programs From M1 to M4 Selective Orthosteric Agonists SELECTIVE SELECTIVE M1 M4 direclidine (NBI - ’568) Enrolling Phase 3 Studies in Schizophrenia Initiating Phase 2 Bipolar Mania Study in Q4 2025 NBI - ’569 Phase 1 Data in 2025 NBI - ’570 Phase 1 Data in 2025 Initiating Phase 2 in Schizophrenia in Q4 2025 NBI - ’567 Phase 1 Data in 2025 Preclinical PREFERRING PREFERRING “Cognition” “Psychosis” DUAL M1 / M4 Combination Therapy to Block Off-target Effects Avoided Acetylcholine Cooperativity Not Required
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29 direclidine* Short-Term Study Design Notes: Primary Endpoint: Change in PANSS Total Score from baseline vs. Placebo at Week 5 Adults with PANSS ≥85, Ages 18-65 (inpatient) Subjects randomized to placebo or direclidine 20 mg QD during the 5-week double-blind treatment period (1:1 randomization) PANSS = Positive & Negative Syndrome Scale; QD = Once-Daily Dosing; PBO = Placebo; Act = Active Treatment (direclidine) Simple Trial Design Testing 20mg QD vs. Placebo with 1:1 Randomization Phase 3 Programs Enrolling with Top-Line Data Expected in 2027 / 2028 direclidine Treatment: 20 mg QD Randomize 1:1 (PBO:Act) Placebo Adult inpatients with PANSS ≥85 Ages 18-65 Safety Follow-Up Visit SCREENING PERIOD 5-WEEK DOUBLE-BLIND TREATMENT PERIOD 1 WEEK * Investigational and not approved in any country
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30 Efficacy, Safety and Tolerability Profile Combined With Once-daily Dosing Supports Advancement to Phase 3 Development Generally Safe and Well-tolerated Across All Doses Tested Summary of direclidine* Positive Phase 2 Topline Results PANSS = Positive & Negative Syndrome Scale; P-values are one-sided. Effect size (Cohen’s D) is based on observed data. Once-Daily 20mg Dose: Efficacy, Safety, and Tolerability Results Support Advancement to Phase 3 Additional Phase 2 Study Details to be Shared at R&D Day on December 16, 2025 • Treatment Discontinuation Rates Due to Adverse Events were Similar Between direclidine and Placebo • Adverse Events with Highest Incidence were Somnolence, Dizziness, and Headache • Nausea, Constipation and Other Gastrointestinal Adverse Events were Low in Frequency / Similar to Placebo • direclidine was Not Associated with a Greater Increase in Weight than Placebo • Enrolling Phase 3 Registrational Studies in Schizophrenia • Initiating Phase 2 study in Bipolar Mania in Q4 2025 • Evaluating Additional Indications for direclidine • Studying Follow-on Compounds in Muscarinic Agonist Portfolio Including: ➢ NBI-’570* (Dual M1 / M4 Agonist) ➢ NBI-’567* (M1-Preferring Agonist) ➢ NBI-’569* (M4-Prefering Agonist) ▪ PANSS Total Score Change: -18.2 ▪ PANSS Total Score Change vs. Placebo: -7.5 (p=0.011) ▪ Effect Size: 0.61 ▪ CGI-S Change vs. Placebo: -0.7 (p<0.001) ▪ Marder Factor Score Change vs. Placebo: • Positive: -3.0 (p=0.004) • Negative: -1.9 (p=0.028) 20mg Once-daily Demonstrated Statistically Significant and Clinically Meaningful Improvements Across Primary and Additional Endpoints * Investigational and not approved in any country
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31 1 Least-squares (LS) means are from a MMRM which includes treatment group, visit, and study period as fixed effects; treatment group-by-visit interaction; baseline PANSS total score as a covariate; and subject as a random effect. 2 Effect size (Cohen’s D) is based on observed data. -5.7 -8.2 -7.7 -9.6 -10.2 -10.8-8.4 -11.5 -13.4 -16.4 -20.2 -18.2 -25 -20 -15 -10 -5 0 Baseline Week 1 Week 2 Week 3 Week 4 Week 5 Week 6 PANSS Total Score Change from Baseline LS Mean1 ± SEM Placebo 20mg * * * *p < 0.05 vs Placebo * Once-Daily 20mg Dose Demonstrated Clinically Meaningful and Statistically Significant Efficacy at Week 3, 4, 5, and 6 Week 4 5 6** PANSS Total Score LS Mean1 -16.4 -20.2 -18.2 LS Mean Difference vs. Placebo1 -6.8 p = 0.008 -10.0 p < 0.001 -7.5 p = 0.011 Effect Size2 0.53 0.72 0.61 20mg QD Efficacy Data Week 4 – Week 6 ** Primary Endpoint = Week 6
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32 *Least-squares (LS) means are from a MMRM which includes treatment group, visit, and study period as fixed effects; treatment group-by-visit interaction; baseline value as a covariate; and subject as a random effect. \ CGI-S Marder Factor — Positive Marder Factor — Negative Week 6 Placebo N=68 20mg QD N=35 Placebo N=68 20mg QD N=35 Placebo N=68 20mg QD N=35 LS Mean Change from Baseline* -0.5 -1.2 -2.8 -5.8 -1.2 -3.1 LS Mean Difference vs. Placebo* -0.7 p < 0.001 -3.0 p = 0.004 -1.9 p = 0.028 Once-Daily 20mg Dose Demonstrated Statistically Significant Improvement in Additional Endpoints
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33 0.56 0.55 0.42 0.41 0.36 0.34 0.3 0.26 Zyprexa (Olanzapine)⁴ Risperdal (Risperidone)⁴ Seroquel (Quetiapine)⁴ Abilify (Aripiprazole)⁴ Latuda (Lurasidone)⁴ Vraylar (Cariprazine)⁴ Caplyta (Lumateperone)⁵ Rexulti (Brexpiprazole)⁴ direclidine* Effect Size Comparable to Known Muscarinic Programs and Leading Antipsychotics Source: 1. Brannan S, et al. N Engl J Med. 2021;384(8):717-726. 2. Krystal J, et al. Lancet. 2022;400(10369):2210– 2220. 3. Kaul I, et al. Lancet. 2024;403(10422):160–170. 4. Kaul I, et al. JAMA Psychiatry. 2024;81(8):749-756. 5. Huhn M, et al. Lancet. 2019;394(10202):939-951. 6. Correll CU, et al. JAMA Psychiatry. 2020;77(4):349-358. Muscarinic Programs Leading Approved Treatments 0.75 0.61 0.61 0.6 125mg / 30mg BID KarXT Ph2 Study¹ 125mg / 30mg BID KarXT Ph3 Study² 20mg direclidine QD Ph2 Study 125mg / 30mg BID KarXT Ph3 Study³ Effect Size Sites 12 22 15 30 Randomization Ratio (active:placebo) 1:1 1:1 2:1 1:1 Weeks of Treatment 5 5 6 5 Date Nov ‘19 Aug ’22 Aug ’24 Mar ‘23 * Investigational and not approved in any country
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34 direclidine* Was Generally Safe and Well Tolerated at All Doses Studied 5.0% Treatment Discontinuation Rate Due to Adverse Events Across All direclidine Arms vs. 4.3% For Placebo \ Placebo N=70 20mg QD N=40 40mg QD N=39 60mg QD N=34 30mg BID N=27 All Treated N=140 Somnolence 2 (2.9) 5 (12.5) 2 (5.1) 7 (20.6) 1 (3.7) 15 (10.7) Dizziness 1 (1.4) 5 (12.5) 3 (7.7) 4 (11.8) 1 (3.7) 13 (9.3) Headache 14 (20.0) 1 (2.5) 5 (12.8) 1 (2.9) 5 (18.5) 12 (8.6) Nausea 2 (2.9) 2 (5.0) 3 (7.7) 3 (8.8) 0 8 (5.7) Constipation 2 (2.9) 2 (5.0) 3 (7.7) 1 (2.9) 1 (3.7) 7 (5.0) Treatment-Emergent Adverse Events Occurring in ≥ 5% of All Treated Groups of direclidine * Investigational and not approved in any country
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35 for direclidine* is the First and Only Muscarinic M4 Selective Orthosteric Agonist in Clinical Development / Phase 3 Studies Large Opportunity For direclidine, A Novel And Differentiated Asset With No Reliance on Innate Acetylcholine Levels, Direclidine is the First and Only Highly Selective Orthosteric M4 Agonist, Potentially Introducing a New Modality for Treatment direclidine Potentially Offers a Compelling and Competitive Benefit-Risk profile Increased Conviction in Indication Expansion Opportunities for direclidine and Neurocrine’s Broad Muscarinic Portfolio Type of Muscarinic Activation Subtype Selectivity Requires Endogenous Ligand (Acetylcholine) Pan Agonism Low Targets M1-M5 No Positive Allosteric Modulation High Targets only M4 Yes Selective Agonism (Direclidine) High Targets only M4 >500-Fold Agonist Selectivity for M4 Receptor Over Other Muscarinic Receptors No Convenience of Once-daily Dosing with or without Food * Investigational and not approved in any country
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36 NBI-’770 (NMDA NR2B NAM)
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37 NBI-’770 (NMDA NR2B Negative Allosteric Modulator) Potent First-in-Class NMDA NR2B NAM Modulator • Oral, Once Daily Antidepressant Effects Mediated via NMDA Pathway • Similar to esketamine, with Potential for Better or Improved Safety Profile • Additional Potential Convenience of Dosing Without Physician Supervision Phase 2 Study Design • 3 Active Arms vs. Placebo • Signal-Seeking Study • Primary Endpoint = MADRS Total Score at Day 5 vs. Baseline (vs. Day 56 in osavampator Phase 3 registrational studies) Expect Phase 2 Top-Line Study Results in Q4 2025 → If Positive, Could Support a Confirmatory Phase 2 Study or Initiation of a Phase 3 Study in MDD NBI-’770* in Phase 2 Proof-of-Concept Study for the Treatment of Major Depressive Disorder * Investigational and not approved in any country
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38 Neurology Pipeline
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39 Neurology Programs in Clinical Development Valbenazine in ATS RESEARCH & DEVELOPMENT STRONG FINANCIAL POSITIONvalbenazine* NBI-’890** and NBI-’675** NBI-’355** • VMAT2 Inhibitor • Phase 3 Study in Dyskinetic Cerebral Palsy Ongoing • Top-Line Data Readout in Q4 2025 • Dyskinetic Cerebral Palsy ✓ Form of Cerebral Palsy (CP) ✓ Affects ~75 – 100K of CP Patients in the U.S. ✓ Can Result in a Range of Developmental Delays, Physical Difficulties and Involuntary Muscle Movements ✓ No Approved Treatments *Investigational for the treatment of dyskinetic cerebral palsy and not approved for this potential indication in any country • Next Generation VMAT2 Inhibitors ✓ NBI-’890 and NBI-’675 are Internally Developed Clinical Candidates ✓ Physicochemical Properties Differentiated from valbenazine ✓ Allow for Long-Acting Injectable Opportunity • Phase 1 Studies Ongoing • Studied for Central Nervous System Indications • Selective Nav1.2 / Nav1.6 Inhibitor • Phase 1 Study Ongoing • Studied as a Potential Treatment for Several Forms of Epilepsy in Adult and Pediatric Patient Populations • Nav1.2 / Nav1.6 ✓ Two Predominant Excitatory Voltage-Gated Sodium Channels in the CNS ✓ Hyperexcitability / Gain of Function of Nav1.2 / Nav1.6 Associated with Several Forms of Epilepsy • In-Licensed from Xenon Pharmaceuticals ** Investigational and not approved in any country
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40 Target Level of Productivity Each Year (On Average) 3+ Phase 3 Programs 2+ Phase 2 Starts 4+ Phase 1 Starts 1 NEW MEDICINE EVERY 2 YEARS For this Steady-State Portfolio Research Multimodality R&D innovation engine Mid-stage pipeline focused on clinically or genetically validated targets Commitment to R&D Sustainability R&D Will Deliver A New Medicine Every Two Years
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41 P R O G R AM ( T A R G E T ) M O D AL I T Y T H E R A P E U T I C A R E A I N D I C A T I ON P H A S E 1 P H A S E 2 P H A S E 3 valbenazine (VMAT2 Inhibitor) Neurology Dyskinetic Cerebral Palsy Osavampator (AMPA PAM) Neuropsychiatry Inadequate Response to Treatment in Major Depressive Disorder Direclidine (M4 Agonist) Neuropsychiatry Schizophrenia NBI-’770 (NMDA NR2B NAM) Neuropsychiatry Major Depressive Disorder NBIP-’1435 (CRF1 Antagonist) Neuroendocrinology Congenital Adrenal Hyperplasia Neuroendocrinology Target Neuroendocrinology Metabolic Disorders Neuroimmunology Target Neuroimmunology CNS/Immunology Indications NBIB-’223 (Frataxin) Neurology Friedreich’s Ataxia NBIB-’233 (GBA1) Neurology Parkinson’s Disease / Gaucher Disease Direclidine (M4 Agonist) Neuropsychiatry Bipolar Mania NBI-’570 (M1/M4 Agonist) Neuropsychiatry Schizophrenia-CNS Indications NBI-‘567 (M1 Agonist) Neuropsychiatry CNS Indications NBI-’569 (M4 Agonist) Neuropsychiatry CNS Indications NBI-’986 (M4 Antagonist) Neurology Movement Disorders NBI-’890 (VMAT2 Inhibitor) Neuropsychiatry CNS Indications NBI-’355 (Nav1.2/1.6 Inhibitor) Neurology Epilepsy NBI-’675 (VMAT2 Inhibitor) Neuropsychiatry CNS Indications Our Pipeline Tomorrow – 17 Programs Peptide Gene Therapy Antibody Small Molecule End of 2025 Current Study Study Initiating Modality Key Study Status Key
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42 Well-Positioned for Sustained & Long-Term Growth *Products commercialized by Neurocrine Biosciences, Inc. in the U.S. • Neurology • Neuroendocrinology • Neuropsychiatry • Neuroimmunology Robust and Sustainable Pipeline Multiple Compounds in Mid- to Late-Stage Studies Rapidly Growing Early-Stage Portfolio TARDIVE DYSKINESIA AND HUNTINGTON’S DISEASE CHOREA COMMERCIAL* $2.50 - $2.55 Billion 2025 INGREZZA Annual Net Sales Guidance Reaffirmed ~$2.1B Cash and Investments as of 09/30/2025 • Strong Balance Sheet • Durable Cash Flows • Attractive P&L Profile RESEARCH & DEVELOPMENT STRONG FINANCIAL POSITION CLASSIC CONGENITAL ADRENAL HYPERPLASIA Therapeutic Area Diversification Well-Defined Capital Structure
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GAAP to Non -GAAP Reconciliations
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Neurocrine Biosciences (Nasdaq: NBIX) Q3 2025 Earnings Presentation October 28 , 2025 Advancing Life -Changing Discoveries in Neuroscience