EX-99.2 3 nbix2024828-exhibit992.htm EX-99.2
Topline Results for Phase 2 Trial of NBI-1117568 (NBI-’568) in Schizophrenia August 28, 2024 Exhibit 99.2 2 Forward Looking Statements 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 regarding the clinical results from, and our future development plans with respect to, NBI-1117568, as well as the therapeutic potential and clinical benefits or safety profile of NBI-1117568. Among the factors that could cause actual results to differ materially from those indicated in the forward-looking statements are: top-line data that we report may change following a more comprehensive review of the data related to the clinical study and such data may not accurately reflect the complete results of the clinical study; risks that clinical development activities may not be initiated or completed on time or at all, or may be delayed for regulatory, manufacturing, or other reasons, may not be successful or replicate previous clinical trial results, may fail to demonstrate that our product candidates are safe and effective, or may not be predictive of real-world results or of results in subsequent clinical trials; risks that regulatory submissions for our product candidates may not occur or be submitted in a timely manner; our future financial and operating performance; risks associated with our dependence on third parties for development, manufacturing, and commercialization activities for our products and product candidates, and our ability to manage these third parties; risks that the FDA or other regulatory authorities may make adverse decisions regarding our products or product candidates; risks that the potential benefits of the agreements with our collaboration partners may never be realized; risks that our products, and/or our product candidates may be precluded from commercialization by the proprietary or regulatory rights of third parties, or have unintended side effects, adverse reactions or incidents of misuse; risks associated with U.S. federal or state legislative or regulatory and/or policy efforts which may result in, among other things, an adverse impact on our revenues or potential revenue; risks associated with potential generic entrants for our products; and other risks described in the Company's periodic reports filed with the Securities and Exchange Commission, including without limitation the Company's quarterly report on Form 10-Q for the quarter ended June 30, 2024. Neurocrine Biosciences disclaims any obligation to update the statements contained in this presentation after the date hereof other than required by law. 3 Agenda Introduction Kevin Gorman, Ph.D. | Chief Executive Officer 1 2 3 Trial Design & Results Eiry Roberts, M.D. | Chief Medical Officer Q&A Kevin Gorman, Ph.D. | Chief Executive Officer Kyle Gano, Ph.D. | Chief Business Development and Strategy Officer Jude Onyia, Ph.D. | Chief Scientific Officer Eiry Roberts, M.D. | Chief Medical Officer Samir Siddhanti | VP Business Development & Muscarinic Agonist Team Lead Jaz Singh, M.D. | VP Clinical Development, Psychiatry 4 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 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 • Treatment discontinuation rates due to adverse events were similar between NBI-’568 and placebo • Adverse events with the highest incidence were somnolence, dizziness, and headache • Nausea, constipation and other gastrointestinal adverse events were low in frequency and similar to placebo • NBI-’568 was not associated with a greater increase in weight than placebo • NBI-’568 Phase 3 program in Schizophrenia expected to begin in early 2025 • Evaluating additional indications for NBI-’568 • Advancing follow-on compounds in muscarinic agonist portfolio ▪ 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

5 Trial Design & Results 6 NBI-’568 Phase 2 Study Design 20 mg QD 30 mg BID Titrate 40 mg QD20 mg 60 mg QD40 mg 20 mg QD Titrate 40 mg QD20 mg 60 mg QD40 mg 20 mg QD 40 mg QD20 mg Randomization 1:1:1 to Placebo:20:40 Randomization 2:1:1:2 to Placebo:20:40:60 Randomization 4:1:1:1:5 to Placebo:20:40:60:30 Titrate Titrate INTERIM ANALYSIS 1 Notes: 60mg QD dose arm added based on safety review 30mg BID dose arm added based on safety review INTERIM ANALYSIS 2 Adults with PANSS ≥80, Ages 18-55 enrolled at 15 US sites (inpatient) Primary Endpoint: Change in PANSS total score from baseline at Week 6 Doses of 60mg QD and 30mg BID were added in a prespecified, blinded fashion by an independent data review committee based on safety and tolerability of previous dose levels Maintained 2:1 randomization ratio (all active doses: placebo) in the study overall Placebo Placebo Placebo PANSS = Positive & Negative Syndrome Scale; QD = Once-Daily Dosing; BID = Twice-Daily Dosing Dose-finding Study Using a First-in-Class Selective M4 Agonist Titrate 7 \ Placebo N=70 20mg QD N=40 40mg QD N=39 60mg QD N=34 30mg BID N=27 All Subjects N=210 Disease Characteristics At Baseline PANSS Total Score, mean 97 97 95 96 98 96 Demographics Age (years), mean 40 41 41 40 41 41 Male: n​ (%) 60 (85.7)​ 31 (77.5)​ 30 (76.9)​ 28 (82.4)​ 22 (81.5)​ 171 (81.4)​ Race:​ n (%) American Indian or​ Alaska Native​ 0​ 0​ 0​ 0​ 1 (3.7)​ 1 (0.5)​ Asian​ 1 (1.4)​ 1 (2.5)​ 0​ 0​ 0​ 2 (1.0)​ Black or​ African American​ 57 (81.4)​ 30 (75.0)​ 28 (71.8)​ 24 (70.6)​ 14 (51.9)​ 153 (72.9)​ White​ 11 (15.7)​ 9 (22.5)​ 10 (25.6)​ 7 (20.6)​ 11 (40.7)​ 48 (22.9)​ Other​ 0​ 0​ 0​ 1 (2.9)​ 1 (3.7)​ 2 (1.0)​ Multiple​ 1 (1.4)​ 0​ 1 (2.6)​ 2 (5.9)​ 0​ 4 (1.9)​ Baseline Characteristics and Demographics Summary 8 Week 6 Placebo N=68 20mg QD N=35 40mg QD N=38 60mg QD N=34 30mg BID N=26 PANSS Total Score LS Mean Change from Baseline* -10.8 -18.2 -12.6 -13.7 -15.8 LS Mean Difference vs. Placebo, p-value* -7.5 p = 0.011​​ -1.9 p = 0.282​ -2.9 p = ​0.189​ -5.0​ p = 0.090 Effect Size** 0.61​ 0.27​ 0.39​ 0.23​ Once-Daily 20mg Dose Met Primary Endpoint *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. **Effect size (Cohen’s D) is based on observed data. PANSS Total Score vs Placebo

9 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 P A N S S T o ta l S c o re C h a n g e f ro m B a s e lin e L S M e a n 1 ± S E M 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 Size​2 ​0.53 0.72 0.61 20mg QD Efficacy Data Week 4 – Week 6 ** Primary Endpoint = Week 6 10 *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 11 NBI-’568 Was Generally Safe and Well Tolerated at All Doses Studied 5.0% Treatment Discontinuation Rate Due to Adverse Events Across All NBI-'568 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 NBI-'568 All Treated Group 12 for NBI-’568 is the First and Only Muscarinic M4 Selective Orthosteric Agonist in Clinical Development Large Opportunity For NBI-'568, A Novel And Differentiated Asset With no reliance on innate acetylcholine levels, NBI-'568 is the first and only highly selective orthosteric M4 agonist, potentially introducing a new modality for treatment. NBI-'568 potentially offers a compelling and competitive benefit-risk profile Increased conviction in indication expansion opportunities for NBI-'568 and Neurocrine’s 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 (NBI-'568) High Targets only M4 >500-fold agonist selectivity for the M4 receptor over other muscarinic receptors No Convenience of once-daily dosing with or without food

13 0.56 0.55 0.42 0.41 0.36 0.34 0.3 0.26 Zyprexa (Olanzapine)⁵ Risperdal (Risperidone)⁵ Seroquel (Quetiapine)⁵ Abilify (Aripiprazole)⁵ Latuda (Lurasidone)⁵ Vraylar (Cariprazine)⁵ Caplyta (Lumateperone)⁶ Rexulti (Brexpiprazole)⁵ NBI-’568 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. Clinical-Stage Muscarinic Programs Leading Approved Treatments 0.75 0.68 0.61 0.61 0.60 125mg / 30mg BID KarXT Ph2 Study¹ 30mg QD Emraclidine Ph1b Study² 125mg / 30mg BID KarXT Ph3 Study³ 20mg NBI-568 QD Ph2 Study 125mg / 30mg BID KarXT Ph3 Study⁴ E ff e c t S iz e Sites 12 5 22 15 30 Randomization Ratio (active:placebo) 1:1 2:1 1:1 2:1 1:1 Weeks of Treatment 5 6 5 6 5 Date Nov ‘19 Jun ’21 Aug ’22 Aug ’24 Mar ‘23 14 Primary Mechanism (M1-M4) Phase Therapeutic Areas Potential Areas For Development NBI-1117568 M4 agonist 2 Psychosis Cognition Alzheimer’s Disease Bipolar Disorder Lewy Body Dementia Parkinson’s Disease Schizophrenia M1 agonist 1 NBI-1117567 M4 agonist 1 NBI-1117570 M1/M4 dual agonist 1 NBI-1076986 M4 antagonist 1 Movement Disorders Dystonia Parkinson’s Disease Tremor NBI-1117568 NBI-1117567 NBI-1117569 NBI-1117570 NBI-1076986 Validation of Selective Orthosteric Agonist Mechanism Strengthens Conviction In Opportunities For Industry Leading Muscarinic Portfolio 15 Summary of Topline Results NBI-'568 20mg once-daily dose demonstrated meaningful improvement in PANSS Total Score at Week 6: • 18.2 point improvement in PANSS Total Score • 7.5 point placebo-adjusted improvement • Effect size of 0.61 NBI-'568 was well tolerated across all doses: • 5.0% treatment discontinuation rate due to adverse events across all NBI-'568 active arms vs. 4.3% for placebo • Nausea, constipation and other gastrointestinal adverse events were low in frequency and similar to placebo • No weight gain relative to placebo Data support advancing NBI-'568 into Phase 3 for schizophrenia NBI-'568 Has A Differentiated Profile Vs. Other Antipsychotics: Novel Mechanism of Action Simple once-daily dosing with or without food GI effects and weight gain similar to placebo PANSS = Positive & Negative Syndrome Scale. Effect size (Cohen’s D) is based on observed data. 16 Q&A Eiry Roberts, M.D. Chief Medical Officer Kevin Gorman, Ph.D. Chief Executive Officer Jude Onyia, Ph.D. Chief Scientific Officer Jaz Singh, M.D. VP Clinical Development, Psychiatry Samir Siddhanti VP Business Development & Muscarinic Agonist Team Lead Kyle Gano, Ph.D. Chief Business Development and Strategy Officer