Core Insights - Neurocrine Biosciences announced that its investigational depression drug NBI-1070770 failed to meet its primary endpoint in a Phase II clinical trial, adding challenges to its collaboration with Takeda Pharmaceuticals [1][2] Group 1: Drug Information - NBI-1070770 is a selective oral NMDA receptor negative allosteric modulator developed for adults with major depressive disorder (MDD) who have insufficient response to at least one antidepressant [2] - The drug's development rights originated from a 2020 collaboration between Neurocrine and Takeda, where Takeda granted exclusive rights to seven investigational drugs, with NBI-1070770 being a key asset for depression [2] Group 2: Clinical Trial Details - The Phase II clinical trial started in March of the previous year, designed as a randomized, multi-center, double-blind, placebo-controlled study, enrolling 73 eligible MDD patients [2] - Patients were allocated in a 1:1:1:3 ratio to three different dosage groups of NBI-1070770 and a placebo group, with a treatment duration of four weeks [2] - The primary endpoint was assessed on day five of treatment using the Montgomery-Åsberg Depression Rating Scale (MADRS) to evaluate changes in depression severity from baseline [2] Group 3: Trial Results and Future Directions - Neurocrine stated that NBI-1070770 was generally well-tolerated during the trial, with no serious adverse events reported, but none of the dosage groups showed statistically significant differences compared to the placebo on the primary endpoint [2] - The Chief Medical Officer expressed disappointment over the results but noted that there are still aspects of the data worth further investigation, and the team will continue to analyze to determine future directions [2] - Despite the Phase II study not meeting its primary endpoint, Neurocrine has other ongoing projects in the depression field, including another drug, osavampator, which showed positive Phase II data and has entered Phase III clinical trials as of January 2025 [2]

Financial Data and Key Metrics Changes - The company reported $790 million in net product sales for Q3 2025, reflecting a 28% year-over-year growth driven by INGREZZA and CRENESSITY [8][10] - CRENESSITY sales grew from $53 million in Q2 to $98 million in Q3, indicating strong early adoption [8][10] - INGREZZA achieved net sales of $687 million, marking the third consecutive quarter of record new patient additions [8][10] Business Line Data and Key Metrics Changes - INGREZZA's performance has been exceptional, with a prescriber base 30% larger than two years ago, and only about 10% of the estimated 800,000 patients with tardive dyskinesia currently treated with a VMAT2 inhibitor [11][12] - CRENESSITY has seen 540 new patients initiate therapy in Q3, bringing the total to over 1,600 since launch, with 80% of dispensed prescriptions now reimbursed [8][15] Market Data and Key Metrics Changes - The company estimates that only half of the patients living with tardive dyskinesia have received a diagnosis, indicating significant growth potential in the market [11][12] - The pediatric population has shown modestly higher demand for CRENESSITY compared to adults, with strong reimbursement rates observed [15] Company Strategy and Development Direction - The company plans to expand its sales force for both INGREZZA and CRENESSITY to accelerate growth and maximize patient share [9][16] - The capital allocation priorities include driving revenue growth, advancing R&D programs, enabling business development, and returning capital to shareholders [10] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the ongoing momentum for both INGREZZA and CRENESSITY, with expectations for continued growth into 2026 and beyond [6][10] - The company is on track to achieve its R&D productivity goals, with multiple Phase I and II study initiations planned [6][10] Other Important Information - The company is fully cooperating with a Department of Justice investigation related to the sales and marketing of INGREZZA, maintaining a robust compliance program [49][50] - The company has $2.1 billion in cash with no debt, allowing for flexibility in capital allocation [94] Q&A Session Summary Question: Insights on patient dynamics and starts for CRENESSITY - Management noted that the adoption of CRENESSITY has been strong, with 540 new treatment forms in Q3, and they do not see significant seasonality affecting the launch [23][24] Question: Implications of the Inflation Reduction Act (IRA) on pricing - Management is awaiting pricing information for Oscado and is preparing to maximize patient numbers on INGREZZA before the IRA impacts begin [31][33] Question: Reimbursement requirements for CRENESSITY - Reimbursement has been smooth, with no specific steroid tapering required for coverage, focusing instead on the underlying disease [39] Question: Sales force expansion details - The sales force expansion is expected to increase overall coverage by about 30%, primarily targeting psychiatry and neurology [58][60] Question: Persistence and compliance of CRENESSITY - Persistence and compliance for CRENESSITY have been strong, with positive feedback on disease control and androgen reduction from healthcare providers [77][78] Question: Future product launches and sales force readiness - The expanded sales force is positioned to support potential launches of new products in the pipeline, including osavampator and Directlidine [109]

Financial Data and Key Metrics Changes - Neurocrine Biosciences reported $790 million in net product sales for Q3 2025, reflecting a 28% year-over-year growth driven by INGREZZA and CRENESSITY [6][10] - CRENESSITY's sales grew from $53 million in Q2 to $98 million in Q3, indicating strong early adoption and persistency rates [6][7] - INGREZZA achieved net sales of $687 million in Q3, marking the third consecutive quarter of record new patient additions [7][10] Business Line Data and Key Metrics Changes - INGREZZA's performance has been exceptional, with a prescriber base that has expanded by 30% over the past two years, reflecting the strong clinical profile and unmet need for tardive dyskinesia treatment [10][11] - CRENESSITY has seen 540 new patients initiate therapy in Q3, bringing the total to over 1,600 since its launch [13][15] - The company anticipates continued growth for both products, with plans for further sales force expansion to maximize patient share [8][16] Market Data and Key Metrics Changes - The tardive dyskinesia market is expected to grow significantly, with only about 10% of diagnosed patients currently treated with a VMAT2 inhibitor, indicating substantial growth potential for INGREZZA [10][11] - The congenital adrenal hyperplasia (CAH) community has shown favorable feedback towards CRENESSITY, with 80% of dispensed prescriptions now being reimbursed [6][15] Company Strategy and Development Direction - Neurocrine Biosciences is focused on expanding its sales force for both INGREZZA and CRENESSITY to accelerate growth into 2026 and beyond [4][8] - The company aims to drive revenue growth, advance R&D programs, enable business development, and return capital to shareholders, with a strong financial profile of over $2.1 billion in cash [9][80] - The strategic expansion of the sales force is intended to maximize patient share and prepare for anticipated launches of investigational psychiatric medicines [8][12] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the ongoing momentum for both products and the potential for sustained long-term growth driven by their science and commitment to patients [5][9] - The company remains on track for its clinical programs, with anticipated top-line results for key studies in the near future [18][19] - Management acknowledged the potential impacts of the Inflation Reduction Act (IRA) on the market and emphasized the importance of maximizing patient share before 2027 [8][30] Other Important Information - The company is fully cooperating with a Department of Justice investigation related to the sales and marketing of INGREZZA, maintaining a robust compliance program [40][41] - The sales force expansion is expected to result in an increase in SG&A expenses of around $150 million in 2026 [9][79] Q&A Session Summary Question: Insights on patient dynamics and starts for CRENESSITY - Management noted that the adoption of CRENESSITY has been strong, with 540 new treatment forms in Q3, and they do not believe there are significant seasonal dynamics affecting enrollment [22][23] Question: Implications of the IRA on pricing and reimbursement - Management is monitoring the upcoming Oscado pricing and its potential effects on INGREZZA, emphasizing the importance of maximizing patient numbers before the IRA impacts [28][30] Question: Status of reimbursement requirements for CRENESSITY - Management indicated that reimbursement has been smooth, with no specific requirements for steroid tapering to continue coverage [34] Question: Sales force expansion details - The expansion is characterized as a 30% increase in overall sales footprint, primarily targeting psychiatry and neurology for INGREZZA, while also expanding the team for CRENESSITY [46][48] Question: Update on the Department of Justice investigation - Management confirmed they are cooperating with the DOJ regarding a civil investigative demand related to INGREZZA's sales and marketing practices [40][41] Question: Progress with CRENESSITY at centers of excellence - All centers of excellence have started adopting CRENESSITY, with varying rates of adoption, and there is optimism about community endocrinologists' engagement [43][44]

Financial Performance - Total Neurocrine net product sales reached $790 million, representing a 16% quarter-over-quarter (QoQ) growth and a 28% year-over-year (YoY) growth compared to Q2 2025 and Q3 2024, respectively[11] - INGREZZA net product sales were $687 million, showing a 10% QoQ growth and a 12% YoY growth compared to Q2 2025 and Q3 2024, respectively[11] - CRENESSITY net product sales amounted to $98 million, including 540 total new patient enrollment forms[11] - The company reaffirmed INGREZZA net sales guidance at $2500 million - $2550 million for the full year 2025[11] - Cash and investments totaled approximately $2100 million as of September 30, 2025[7] Research and Development - The company initiated all Phase 3 registrational studies for osavampator (AMPA PAM) as an adjunctive therapy for the treatment of MDD in adults and direclidine (Selective M4 Agonist) for the treatment of Schizophrenia[11] - The company expects to report top-line data in Q4 2025 for the Phase 3 study of valbenazine for Dyskinetic Cerebral Palsy and the Phase 2 study of NBI-'770 (NMDA NR2B NAM) for the treatment of MDD[11] - The company plans to initiate Phase 2 studies in Q4 2025 for direclidine for Bipolar Mania and NBI-'570 (Selective Dual M1 / M4 Agonist) for Schizophrenia[11] Commercial Strategy - The company plans to expand INGREZZA and CRENESSITY sales teams in Q4 2025, with completion expected by the end of Q1 2026, to maximize commercial momentum[11] - CRENESSITY has achieved approximately 80% reimbursement coverage for dispensed scripts[11] Pipeline Development - The company has a pipeline of 12 programs, including the first biologic program NBIP-'1435[8] - The company is advancing additional internally developed pre-clinical programs, including biologics, into first-in-human studies[11]

Core Insights - Neurocrine Biosciences, Inc. announced new data from the Phase 2 SAVITRI study demonstrating significant improvement in depression severity at Day 28 and Day 56 with the administration of 1 mg osavampator (NBI-1065845) [1] Group 1 - The Phase 2 SAVITRI study showed statistically significant improvement in depression severity [1] - The improvement was clinically meaningful at both Day 28 and Day 56 [1] - The treatment involved once-daily oral administration of 1 mg osavampator [1]

Summary of Neurocrine Biosciences FY Conference Call Company Overview - **Company**: Neurocrine Biosciences (NasdaqGS:NBIX) - **Date**: September 17, 2025 - **Key Speakers**: Kyle Gano (CEO), Sanjay Keswani (CMO), Todd Tushla (VP of Investor Relations) Key Points R&D Strategy and Pipeline - Neurocrine is shifting its R&D strategy to focus on internal drug discovery rather than solely in-licensing programs, aiming to enhance R&D productivity [2][3] - The company plans to initiate four new phase 1 programs, two new phase 2 programs, and maintain at least three programs in phase 3 development annually, potentially leading to one new medicine every two years [4] - Therapeutic areas of focus include neurology, psychiatry, endocrinology, and immunology, with a particular emphasis on CNS-related targets [5][6] Portfolio Risk Management - The current portfolio is weighted more towards psychiatry due to recent successes, with future expectations of a balanced distribution: 40-50% neurology, 20-30% psychiatry, 10-20% endocrinology, and 10-20% immunology [8][9] Specific Programs - **NBI-770**: An NMDA negative allosteric modulator for major depressive disorder (MDD), aiming for efficacy similar to Spravato but with fewer side effects. Phase 2 data expected by late 2025 [10][11] - The study involves 72 patients, focusing on changes in MADRS scores by day five [11][12] - **Osavampator**: An AMPA potentiator with positive phase 2 data, showing significant efficacy and a favorable safety profile. Phase 3 trials are ongoing, with data expected in 2027 [16][19] - The most effective dose showed a MADRS effect size of 0.55 to 0.75, indicating strong efficacy [19][20] - **NBI-568**: A treatment for schizophrenia, with phase 2 results showing a significant improvement in PANSS scores. The best-performing dose was 20 mg once daily, with a placebo-corrected improvement of 7.5 points and an effect size of 0.61 [35][37] Market Performance and Financials - In Q2, Neurocrine reported $682 million in revenue, a 17% year-over-year growth, driven by Ingrezza and CRENESSITY [54][55] - Ingrezza achieved record back-to-back NRX quarters and a record TRX quarter in Q2, indicating strong market performance [54] Future Outlook - The company is optimistic about its evolving R&D strategy and the potential of its pipeline to address significant unmet needs in neuropsychiatric conditions [6][55] - The focus on validated biological pathways and diverse mechanisms of action aims to enhance treatment options for patients with major depressive disorder and schizophrenia [27][50] Additional Insights - The company emphasizes the importance of safety and tolerability in its drug development, particularly for chronic psychiatric conditions [50] - Neurocrine's approach to managing clinical trials aims to simplify processes and enhance the likelihood of positive outcomes, learning from past industry experiences [43][45] This summary encapsulates the key discussions and insights from the Neurocrine Biosciences FY Conference Call, highlighting the company's strategic direction, pipeline developments, and market performance.

Core Insights - Neurocrine Biosciences, Inc. will present new data from the Phase 2 SAVITRI study of osavampator for adults with major depressive disorder at Psych Congress 2025 [1] Group 1 - The SAVITRI study's top-line results were initially announced in April 2024 [1] - The poster presentation has been selected as a finalist for the Psych Congress Poster Awards [1] - The event will take place from September 17-21, 2025, in San Diego [1]

Company Highlights - Neurocrine expects $2.5 billion in sales for INGREZZA this year, indicating strong market performance [3] - The launch of CRENESSITY, the first new medicine in over 70 years for congenital adrenal hyperplasia, has started off strongly [3] - Neurocrine has initiated two major Phase III programs: one for osavampator targeting major depressive disorder and another for a muscarinic program related to schizophrenia [4]

Financial Performance - Total Neurocrine net product sales reached $682 million in Q2 2025, representing a 21% quarter-over-quarter (QoQ) growth and a 17% year-over-year (YoY) growth compared to Q1 2025 and Q2 2024, respectively [11] - INGREZZA net product sales were $624 million in Q2 2025, reflecting a 15% QoQ growth and an 8% YoY growth compared to Q1 2025 and Q2 2024, respectively [11] - CRENESSITY net product sales amounted to $53 million in Q2 2025, including 664 total new patient enrollment forms [11] - The company narrowed INGREZZA net sales guidance for 2025 to $2.50 - $2.55 billion, reflecting double-digit volume growth partially offset by a lower net price due to expanded access [7, 11] - Cash and investments totaled approximately $1.8 billion as of June 30, 2025 [7] Research and Development - The company initiated all Phase 3 registrational programs for osavampator (AMPA PAM) for MDD and NBI-'568 (Selective M4 Agonist) for schizophrenia [11] - A Phase 1 study was initiated for NBIP-'1435, a long-acting CRF-1 receptor antagonist, for the potential treatment of classic CAH [11] - Phase 2 studies are expected to be initiated for NBI-'568 in bipolar mania and NBI-'570 (Selective Dual M1 / M4 Agonist) for schizophrenia [11] - Top-line data is expected to be reported in Q4 2025 for the Phase 3 study of valbenazine for dyskinetic cerebral palsy and the Phase 2 study of NBI-'770 (NMDA NR2B NAM) for the treatment of MDD [11] Pipeline and Portfolio - The company has a pipeline of 12 programs, including the first biologic program NBIP-'1435 [8] - The company expects Phase 1 muscarinic agonist results for NBI-'567 (Selective M1 Agonist), NBI-'569 (Selective M4 Agonist), and NBI-'570 [11]

Financial Performance & Guidance - INGREZZA net product sales reached $545 million in Q1 2025, representing an 8% year-over-year growth[12] - CRENESSITY net product sales were $145 million in Q1 2025, including 413 total patient enrollment forms[11] - The company reaffirms INGREZZA net sales guidance of $250 billion to $260 billion for 2025[6, 11] - Cash and investments totaled approximately $18 billion as of March 31, 2025[6] - Non-GAAP R&D expense was $2402 million in Q1 2025, an increase from $1424 million in Q1 2024[12] - Non-GAAP SG&A expense was $245 million in Q1 2025, compared to $216 million in Q1 2024[12] Pipeline Development - Phase 3 registrational program initiated for osavampator as an adjunctive therapy for the treatment of MDD in adults[11] - Phase 1 studies initiated for NBI-'355 (Nav12 / 16 Inhibitor) for Epilepsy and NBI-'675 (VMAT2 Inhibitor) for Movement Disorders[11] Market & Product - Approximately 800000 people in the US are estimated to be affected by Tardive Dyskinesia[21] - Chorea affects approximately 90% of the 40000 patients with Huntington's Disease in the US[24] - CRENESSITY is the first new treatment available for Classic CAH in 70 years, targeting approximately 20000 pediatric and adult patients in the US[30, 31]