Core Insights - Neurocrine Biosciences appointed Lewis Choi as Chief Information Officer, effective June 9, 2025, to lead the company's technology initiatives [1][2] - Choi brings 25 years of experience in information technology and artificial intelligence, previously serving at Thermo Fisher Scientific [2] - The company is focused on advancing its technology to support the launch of CRENESSITY, growth of INGREZZA, and development of its pipeline [2] Company Overview - Neurocrine Biosciences is a biopharmaceutical company dedicated to developing treatments for neurological, neuroendocrine, and neuropsychiatric disorders [3] - The company has a diverse portfolio that includes FDA-approved treatments for conditions such as tardive dyskinesia and Huntington's disease, along with a robust pipeline in mid- to late-phase clinical development [3] - The mission of the company is to relieve suffering for patients with significant unmet medical needs through innovative neuroscience [3]

Core Insights - Investors in the Medical - Drugs sector may find Catalyst Pharmaceutical (CPRX) and Neurocrine Biosciences (NBIX) to be potential investment opportunities, with a need to evaluate which stock is more appealing for value investors [1] Valuation Metrics - CPRX has a forward P/E ratio of 11.09, significantly lower than NBIX's forward P/E of 32.88, indicating that CPRX may be undervalued [5] - The PEG ratio for CPRX is 0.98, while NBIX has a PEG ratio of 1.28, suggesting that CPRX offers better value relative to its expected earnings growth [5] - CPRX's P/B ratio stands at 3.82 compared to NBIX's P/B of 4.86, further supporting the notion that CPRX is more attractively valued [6] Zacks Rank and Earnings Outlook - Currently, CPRX holds a Zacks Rank of 2 (Buy), while NBIX has a Zacks Rank of 3 (Hold), indicating a more favorable earnings outlook for CPRX [3] - The positive revisions in earnings estimates for CPRX suggest an improving earnings outlook, which is a critical factor for value investors [3][7] Value Grades - CPRX has received a Value grade of A, while NBIX has a Value grade of C, reflecting the stronger valuation metrics and estimate revision activity for CPRX [6][7]

Core Insights - Neurocrine Biosciences announced new data from the Phase 4 KINECT-PRO study showing significant improvements in physical, social, and emotional functioning in patients with tardive dyskinesia treated with INGREZZA [1][6][4] Group 1: Study Overview - KINECT-PRO is the first study to evaluate patient-reported outcomes with INGREZZA using multiple validated scales, including the Tardive Dyskinesia Impact Scale [1][6] - The study enrolled 59 patients who received once-daily INGREZZA (40 mg, 60 mg, or 80 mg) for up to 24 weeks, with 52 patients completing the Week 24 visit [2][4] Group 2: Study Objectives and Measures - The primary objective was to assess changes in patient-reported physical and socio-emotional impacts of tardive dyskinesia during treatment [3] - Outcomes were measured at Weeks 4, 8, 16, and 24 using the Tardive Dyskinesia Impact Scale, Sheehan Disability Scale, and EQ Visual Analogue Scale [3] Group 3: Results and Improvements - Improvements in TDIS, SDS, EQ-VAS, and AIMS were observed as early as Week 4 and sustained through Week 24, indicating robust and clinically meaningful enhancements in functioning [4][6] - The mean change from baseline at Week 24 for the overall population showed a reduction of -8.0 in TDIS, -2.3 in social life, -1.6 in family life, an increase of +13.1 in EQ-VAS, and a reduction of -6.8 in AIMS total score [5] Group 4: Subgroup Analysis - Both mild and moderate/severe tardive dyskinesia subgroups showed significant improvements, with mild TD subgroup reporting a mean change of -6.8 in TDIS and +12.8 in EQ-VAS [5][7] - The moderate/severe TD subgroup reported a mean change of -8.9 in TDIS and +13.3 in EQ-VAS [7] Group 5: Safety and Tolerability - The safety and tolerability profile of INGREZZA was consistent with known data, with no new safety concerns identified during the study [7][6]

Core Insights - Neurocrine Biosciences announced significant improvements in symptoms and overall severity of schizophrenia in adults from the Phase 2 study of NBI-1117568, the first oral muscarinic M4 selective orthosteric agonist in clinical development for this condition [1][2][6] Company Overview - Neurocrine Biosciences is focused on developing treatments for neurological, neuroendocrine, and neuropsychiatric disorders, with a diverse portfolio that includes FDA-approved treatments and a robust pipeline of compounds in clinical development [13] Study Details - The Phase 2 study involved 210 adults aged 18 to 55 with schizophrenia, randomized to receive either NBI-1117568 or placebo over a six-week period, followed by a two-week safety follow-up [2][9] - The primary endpoint was the change in total Positive and Negative Syndrome Scale (PANSS) score from baseline to Week 6, showing statistically significant improvements with the 20 mg dose of NBI-1117568 by Week 3 [4][6] Safety and Tolerability - NBI-1117568 was generally safe and well tolerated, with treatment discontinuation rates due to adverse events similar to placebo; common adverse events included somnolence (10.7% vs 2.9%) and dizziness (9.3% vs 1.4%) [3][6] Future Development - Based on positive Phase 2 results, a Phase 3 registrational program has been initiated to further evaluate the efficacy, safety, and tolerability of NBI-1117568, expected to enroll approximately 280 patients [6][9]

Summary of Neurocrine's Conference Call Company Overview - **Company**: Neurocrine Biosciences - **Key Products**: Pranesity, INGREZZA - **Financial Guidance**: Expected revenue of $2.5 to $2.6 billion for the year [5][41] Core Insights and Arguments Product Launch and Performance - **Pranesity Launch**: Launched in December, first treatment for congenital adrenal hyperplasia in over 70 years; exceeded expectations with over 400 treatment forms submitted in Q1 [6][16] - **INGREZZA Performance**: Despite a challenging environment, INGREZZA showed better-than-expected performance in Q1, with a record number of new patient starts [33][41] Market Dynamics - **Diagnosis Rates**: For INGREZZA, diagnosis rates have increased from 2% at launch to 40% currently, but only 10% of diagnosed patients are being treated [5][34] - **Patient Population**: Estimated 20,000 classic congenital adrenal hyperplasia patients in the U.S., primarily treated by endocrinologists [14][15] Financial Position - **Cash Reserves**: Neurocrine has $1.8 billion in cash, reflecting financial flexibility despite using $750 million to retire convertible debt [9] - **Reimbursement Success**: 70% of Pranesity prescriptions were commercially reimbursed in Q1, exceeding expectations [31] Additional Important Points Clinical Trials and Pipeline - **Osvampir and M4 Agonist Programs**: Two major phase three programs underway, focusing on major depressive disorder and schizophrenia [7][9] - **Patient Engagement**: Early patient engagement and education efforts contributed to the successful launch of Pranesity [13][21] Market Challenges - **Competitive Dynamics**: The market for INGREZZA faced challenges due to competitive pressures and payer dynamics, leading to a slowdown in new patient starts in late 2022 [34][36] - **Reauthorization Process**: Many existing patients require reauthorization at the beginning of the year, impacting Q1 performance [37] Future Outlook - **Growth Expectations**: Anticipated continued growth in new patient starts and overall revenue, with confidence in the sales team's productivity [41][42] - **Contracting Strategy**: Entering into contracts with payers to ensure patient retention and facilitate new patient additions [39][40]

Core Insights - Neurocrine Biosciences announced significant findings from the Phase 3 CAHtalyst Pediatric study, demonstrating lasting reductions in glucocorticoid doses and improvements in clinical outcomes for pediatric patients with classic congenital adrenal hyperplasia (CAH) treated with CRENESSITY (crinecerfont) for up to one year [1][2][12] Group 1: Clinical Study Findings - The Phase 3 CAHtalyst Pediatric study included 103 pediatric patients aged 4 to 17 years, making it the largest interventional clinical trial program for classic CAH [2][10] - Patients receiving CRENESSITY showed a mean glucocorticoid dose reduction from 16.4 mg/m²/d at baseline to 13.5 mg/m²/d at Week 52, a decrease of 2.9 mg/m²/d [3] - Improvements in clinical outcomes included a reduction in mean body mass index (BMI) standard deviation scores by -0.09 in the CRENESSITY group compared to -0.02 in the placebo group [3] Group 2: Hormonal and Clinical Outcomes - Adrenocorticotropic hormone (ACTH), 17-hydroxyprogesterone (17-OHP), and androstenedione (A4) levels remained below baseline levels in patients treated with CRENESSITY, despite reduced glucocorticoid doses [1][4] - The proportion of patients achieving glucocorticoid doses within the physiologic range (≤11 mg/m²/d hydrocortisone equivalents) remained stable from Week 28 (30%) to Week 52 (32%) [4] Group 3: Safety and Tolerability - CRENESSITY was generally well tolerated, with no adrenal crises reported during the double-blind placebo-controlled (DBPC) period [5] - The most common adverse reactions included headache (25% vs. 6% for placebo), abdominal pain (13% vs. 0%), and fatigue (7% vs. 0%) [5] Group 4: Treatment Implications - CRENESSITY allows for a reduction in glucocorticoid doses while maintaining or improving hormonal levels, potentially transforming the treatment landscape for children and adolescents with classic CAH [2][14] - The study supports the ongoing use of CRENESSITY in conjunction with glucocorticoids for effective management of CAH [16]

Core Insights - Neurocrine Biosciences presented new analyses from a Phase 4 randomized withdrawal study showing that patients with tardive dyskinesia who continued treatment with INGREZZA® (valbenazine) capsules reported improvements in functional and health-related quality of life measures [1][2] - The findings were presented at the 2025 ISPOR Conference, highlighting the clinically meaningful improvements in patients' quality of life due to INGREZZA treatment [1][2] Study Details - The analyses were based on data from 127 patients in a Phase 4, double-blind, placebo-controlled study, where patients received up to 80 mg of INGREZZA for eight weeks before being randomized to continue treatment or receive a placebo for an additional eight weeks [2][3] - Significant improvements were observed in health-related quality of life (HRQoL) measures, including mobility, self-care, usual activities, and pain/discomfort, with placebo-adjusted differences noted in anxiety/depression and mobility [3][4] Health-Related Quality of Life Improvements - Patients receiving INGREZZA for eight weeks showed improvements in HRQoL dimensions, with changes from baseline reported as follows: mobility (-0.27), self-care (-0.28), usual activities (-0.36), and pain/discomfort (-0.34) [3] - Continued treatment for an additional eight weeks resulted in further improvements, including a placebo-adjusted difference in mobility of -0.34 and anxiety/depression of -0.38 compared to the placebo group [3] Functional Impairment Improvements - In the open-label portion of the study, patients reported significant improvements in work/school (-1.37), social life (-1.65), family/home life (-1.30), and total Sheehan Disability Scale (SDS) score (-4.28) after eight weeks of treatment [4] - Continued treatment for an additional eight weeks led to further improvements in social life (-0.95) and family/home life (-0.89) compared to those receiving placebo [4] About INGREZZA - INGREZZA is a selective vesicular monoamine transporter 2 (VMAT2) inhibitor approved for treating adults with tardive dyskinesia and chorea associated with Huntington's disease [12][13] - The drug is designed to inhibit dopamine release, potentially reducing uncontrollable movements associated with these conditions [13][14]

Core Insights - Neurocrine Biosciences announced positive Phase 3 data for CRENESSITY (crinecerfont) in treating congenital adrenal hyperplasia (CAH), showing significant improvements in hormone levels and glucocorticoid dose reductions in both pediatric and adult patients [1][3][16] Group 1: Study Results - In the pediatric study, 90% of participants on CRENESSITY achieved at least one threshold for androstenedione reduction or glucocorticoid reduction, compared to 21% on placebo [7][8] - At Week 28, 30% of pediatric participants on CRENESSITY reached a physiologic glucocorticoid dose while maintaining or improving androstenedione levels, whereas no placebo participants achieved this [8] - In the adult study, at Week 24, 47% of male patients on CRENESSITY normalized luteinizing hormone (LH) levels compared to 22% on placebo [10] Group 2: Treatment Mechanism - CRENESSITY is a novel oral corticotropin-releasing factor type 1 receptor antagonist that aims to reduce excess adrenal androgens and allow for lower glucocorticoid doses, addressing complications from high-dose steroid use [3][17] - The drug works by decreasing adrenocorticotropic hormone (ACTH) levels, which in turn reduces the production of adrenal androgens, potentially alleviating symptoms associated with CAH [17] Group 3: Safety and Tolerability - CRENESSITY was generally well tolerated in pediatric patients, with no adrenal crises reported during the double-blind treatment period [5] - The most common adverse reactions in pediatric patients included headache (25% vs. 6% for placebo) and abdominal pain (13% vs. 0%) [5] - In adult patients, 1.6% experienced adrenal crisis while on CRENESSITY, with common side effects including fatigue (25% vs. 15% for placebo) and headache (16% vs. 15%) [10]

Core Viewpoint - Grifols (GRFS) is currently positioned as a better value opportunity compared to Neurocrine Biosciences (NBIX) based on various valuation metrics and earnings outlook [1][3]. Valuation Metrics - GRFS has a forward P/E ratio of 7.65, significantly lower than NBIX's forward P/E of 31.35, indicating that GRFS may be undervalued [5]. - The PEG ratio for GRFS is 0.26, while NBIX's PEG ratio is 1.22, suggesting that GRFS has a more favorable earnings growth outlook relative to its price [5]. - GRFS's P/B ratio stands at 0.60, compared to NBIX's P/B of 4.63, further highlighting GRFS's relative undervaluation [6]. Earnings Outlook - GRFS has a Zacks Rank of 2 (Buy), indicating a stronger improvement in its earnings outlook compared to NBIX, which has a Zacks Rank of 3 (Hold) [3][6]. - The overall valuation metrics and solid earnings outlook position GRFS as the superior value option in the current market [6].

Summary of Neurocrine's Conference Call Company Overview - **Company**: Neurocrine Biosciences - **CEO**: Kyle Gano, appointed in October 2023 Macro Issues - **Executive Order on Most Favored Nation**: - Uncertainty regarding the impact on Neurocrine due to lack of details on the executive order [3][4][5][6] - Focus on building a resilient business amidst evolving regulations [6][7] - **Tariffs**: - Tariffs are not expected to significantly impact the cost of goods for Neurocrine's products [9][10] - **FDA Interactions**: - No current NDA reviews; recent interactions focused on Phase II discussions for upcoming Phase III programs [11][12] Product Launch: Crinesity (Canestrafont) - **Sales Performance**: - Recognized $14.5 million in sales with over 400 new patient starts in the last quarter [16] - Impressive reimbursement rate of approximately 70% [16][18] - **Launch Strategy**: - The launch is described as "measured" due to the need for physician education and patient awareness [18][20] - Patients must navigate insurance processes, which may delay prescriptions [20][21] - **Patient Demographics**: - Initial patient population is skewed towards pediatrics due to more frequent physician visits [27][32] - Adult women are expected to show more motivation for treatment compared to men [49] - **Direct-to-Consumer Advertising**: - Traditional advertising may be less effective due to the smaller patient population for congenital adrenal hyperplasia (CAH) [34][36] - **Market Potential**: - Crinesity is viewed as a potential blockbuster, with expectations of significant market uptake [38][39] Competitive Landscape - **Differentiation**: - Neurocrine's approach with Crinesity is based on efficacy, safety, and tolerability, which are critical for patient adoption [43][46] - The company aims to treat the majority of patients with CAH before competitors enter the market [45][46] Pipeline Developments - **Upcoming Data Readouts**: - Phase III trials for osavapitur and MBI-568 are anticipated [52] - Studies on valbenazine for dyskinesia associated with cerebral palsy and adjunctive treatment for schizophrenia are ongoing [56][60] - **Muscarinic Agonists**: - Neurocrine is developing multiple muscarinic agonists, focusing on selective activation to improve efficacy and safety [70][72] Financial Outlook - **Investment in Growth**: - The company is prioritizing growth over immediate profitability, with significant investments in sales and marketing for Crinesity and INGREZZA [77][78] - R&D spending is projected to be in the mid-30% range of net revenue due to ongoing Phase III trials [79] Conclusion - Neurocrine is navigating a complex regulatory environment while launching Crinesity, which shows promising early sales. The company is focused on educating physicians and patients, with a strong pipeline and strategic investments aimed at long-term growth and market leadership in the treatment of CAH and other conditions.