Form 8-K - Current report

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): August 28, 2024

NEUROCRINE BIOSCIENCES, INC.

(Exact name of Registrant as Specified in Its Charter)


Delaware	0-22705	33-0525145
(State or Other Jurisdiction	(Commission	(IRS Employer
of Incorporation)	File Number)	Identification No.)

6027 Edgewood Bend Court
San Diego,	California	92130
(Address of Principal Executive Offices)		(Zip Code)

(858) 617-7600

(Registrant’s telephone number, including area code)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

☐ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

☐ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

☐ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

☐ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:


Title of each class	Trading Symbol	Name of each exchange on which registered

Common Stock, $0.001 par value	NBIX	Nasdaq Global Select Market

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).

Emerging growth company ☐

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

Item 7.01. Regulation FD Disclosure.

On August 28, 2024, Neurocrine Biosciences, Inc. (“Neurocrine” or the “Company”) issued a press release announcing positive top-line data for its Phase 2 clinical study of NBI-1117568 in adults with schizophrenia, a copy of which is furnished as Exhibit 99.1 to this Current Report on Form 8-K. The Company will hold a live conference call and webcast to discuss the clinical data on August 28, 2024 at 8:00 a.m. Eastern Time (5:00 a.m. Pacific Time). The Company will make available a slide presentation to accompany the call, a copy of which is furnished as Exhibit 99.2 to this Current Report on Form 8-K.

The information in this Item 7.01, including Exhibit 99.1 and Exhibit 99.2 attached hereto, is intended to be furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such filing.

Item 8.01. Other Events.

On August 28, 2024, Neurocrine announced positive top-line data for its Phase 2 clinical study of NBI-1117568 (“NBI-’568”) in adults with schizophrenia. NBI-’568 is the first investigational, oral, muscarinic M4 selective agonist in development for the treatment of schizophrenia.

The NBI-’568-SCZ2028 dose-finding study met its primary endpoint for the once-daily 20 mg dose. It demonstrated a clinically meaningful and statistically significant reduction from baseline in the Positive and Negative Syndrome Scale (PANSS) total score at Week 6 with a placebo-adjusted mean reduction of 7.5 points (p=0.011 and effect size of 0.61) and an 18.2-point reduction from baseline. The once-daily 20 mg dose also demonstrated a statistically significant improvement for additional endpoints, including improvement in the Clinical Global Impression of Severity (CGI-S) scale, Marder Factor Score – Positive Symptom Change, and Marder Factor Score – Negative Symptom Change.

NBI-’568 was generally safe and well-tolerated at all doses studied in the Phase 2 clinical trial. 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. Gastrointestinal adverse events including nausea and constipation were low in frequency and similar to placebo. Cardiovascular-related events were also low in frequency and were not deemed to have clinical relevance at any dose tested. NBI-’568 was not associated with a greater increase in weight than placebo. Few extrapyramidal symptoms adverse events were reported.

Neurocrine currently expects to advance NBI-’568 into Phase 3 development in early 2025.

Primary Endpoint Results Summary


Week 6 (Day 42)	Placebo (N=68)	20 mg QD (N=35)	40 mg QD (N=38)	60 mg QD (N=34)	30 mg 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*	-	-7.5 (p=0.011)	-1.9 (p=0.282)	-2.9 (p=0.189)	-5 (p=0.090)
Effect Size**	-	0.61	0.27	0.39	0.23

* 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.

About the NBI-1117568-SCZ2028 Phase 2 Clinical Study

The Phase 2, multicenter, randomized, double-blind, placebo-controlled, multi-arm, multi-stage inpatient dose-finding study was designed to assess the efficacy, safety, tolerability, and pharmacokinetics (PK) of NBI-’568 compared with placebo in adult subjects with a primary diagnosis of schizophrenia who are experiencing an acute exacerbation or relapse of symptoms. The study enrolled 210 participants.

Next Steps for Neurocrine’s Muscarinic Portfolio

In addition to NBI-’568, Neurocrine has a broad portfolio of assets in clinical development that selectively target muscarinic receptors. The Company’s muscarinic agonist portfolio also includes NBI-1117567, NBI-1117569, and NBI-1117570, which the Company acquired the rights to develop and commercialize from Nxera Pharma (formerly Sosei Heptares). Neurocrine is also developing NBI-1076986, a selective M4 antagonist that was discovered and is being developed internally at Neurocrine.

Forward-Looking Statements

In addition to historical facts, this Current Report on Form 8-K and certain of the materials furnished herewith contain 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 disclaims any obligation to update these forward-looking statements after the date hereof other than required by law.

Item 9.01. Financial Statements and Exhibits.

(d) Exhibits


Exhibit No.						Description

99.1						Press Release issued by Neurocrine Biosciences, Inc. on August 28, 2024

99.2						Slide Presentation dated August 28, 2024

104						Cover Page Interactive Data File (embedded within the Inline XBRL document)

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.


			NEUROCRINE BIOSCIENCES, INC.

Dated: August 28, 2024			/s/ Darin M. Lippoldt
			Darin M. Lippoldt
			Chief Legal Officer

Exhibit 99.1

Neurocrine Biosciences Reports Positive Phase 2 Data for NBI-1117568

in Adults with Schizophrenia

•The Once-Daily 20 mg Dose Met the Primary Endpoint, Demonstrating a Statistically Significant 7.5-Point Improvement (p=0.011, 0.61 Effect Size) in the PANSS Total Score Compared to Placebo at Week 6 with an 18.2-Point PANSS Total Score Improvement from Baseline

•The Once-Daily 20 mg Dose Met Additional Endpoints, Demonstrating Statistically Significant Improvements in Clinical Global Impression of Severity Scale and Marder Factor Score Positive Symptom Change and Negative Symptom Change

•NBI-’568 Was Generally Safe and Well Tolerated at All Doses Studied

•The Once-Daily 20 mg Dose Efficacy, Safety and Tolerability Phase 2 Results Support Advancement to Phase 3 in Schizophrenia in Early 2025

•Company to Host Conference Call with Management at 8 a.m. EDT

SAN DIEGO, August 28, 2024 – Neurocrine Biosciences, Inc. (Nasdaq: NBIX) today announced positive top-line data for its Phase 2 clinical study of NBI-1117568 (NBI-’568) in adults with schizophrenia. NBI-’568 is the first investigational, oral, muscarinic M4 selective agonist in development for the treatment of schizophrenia.

“This Phase 2 dose-finding study delivered on our goal of identifying a once-daily, well tolerated dosing regimen with a compelling and competitive benefit-risk profile,” said Eiry Roberts, M.D., Chief Medical Officer at Neurocrine Biosciences. “We recognize the significant need for new and innovative medicines to treat schizophrenia and look forward to advancing NBI-’568, the first M4 selective agonist, into Phase 3 development early next year.”

“NBI-1117568 demonstrated a clinically meaningful and statistically significant reduction in PANSS scores and was well tolerated, importantly with minimal GI effects and no weight gain relative to placebo,” said Dr. Maurizio Fava, Psychiatrist-in-Chief at Massachusetts General Hospital of Harvard University. “As a selective M4 orthosteric agonist, the potential of NBI-1117568 as an option that could reduce symptoms of schizophrenia with fewer side effects would be a welcome alternative to current treatments for patients and caregivers.”

Primary Endpoint Results Summary


Week 6 (Day 42)	Placebo (N=68)	20 mg QD (N=35)	40 mg QD (N=38)	60 mg QD (N=34)	30 mg 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*	-	-7.5 (p=0.011)	-1.9 (p=0.282)	-2.9 (p=0.189)	-5 (p=0.090)
Effect Size**	-	0.61	0.27	0.39	0.23

** Effect size (Cohen’s D) is based on observed data.

Next Steps for Neurocrine Biosciences’ Muscarinic Portfolio

In addition to NBI-’568, Neurocrine Biosciences has a broad portfolio of assets in clinical development that selectively target muscarinic receptors. The company’s muscarinic agonist portfolio also includes NBI-1117567, NBI-1117569, and NBI-1117570, which the company acquired the rights to develop and commercialize from Nxera Pharma (formerly Sosei Heptares). Neurocrine Biosciences is also developing NBI-1076986, a selective M4 antagonist that was discovered and is being developed internally at Neurocrine.

Compound

Primary Mechanism
(M1-M4)

Phase

Therapeutic
Areas

Potential Areas for Development

NBI-1117568

M4 agonist

Psychosis
Cognition

Alzheimer’s Disease
Bipolar Disorder
Lewy Body Dementia
Parkinson’s Disease
Schizophrenia

NBI-1117567

M1 agonist

NBI-1117569

M4 agonist

NBI-1117570

M1/M4 dual agonist

NBI-1076986

M4 antagonist

Movement Disorders

Dystonia
Parkinson’s Disease Tremor

Conference Call and Webcast Today at 8:00 AM Eastern Time

Neurocrine Biosciences will hold a live conference call and webcast today at 8:00 a.m. Eastern Time (5:00 a.m. Pacific Time). Participants can access the live conference call by dialing 800-579-2543 (U.S.) or 785-424-1789 (International) using the conference ID: NBIX. The live webcast and accompanying slides can be accessed on the investor relations section of Neurocrine Biosciences’ website here. A replay of the webcast will be available on the website approximately one hour after the conclusion of the event and will be archived for approximately one month.

About NBI-1117568

NBI-’568 is the first and only M4 selective orthosteric agonist in clinical development. There are five muscarinic acetylcholine receptors involved in neurotransmission. Muscarinic receptors are central to brain function and validated as drug targets in psychosis and cognitive disorders. As an M4 selective orthosteric agonist, NBI-’568 offers the potential for a novel mechanism with an improved safety profile without the need of combination therapy to minimize off-target pharmacology-related side effects, while also not being dependent on the presence of acetylcholine for efficacy.

About the NBI-1117568-SCZ2028 Phase 2 Clinical Study

About Schizophrenia

Schizophrenia is a serious and complex syndrome with heterogeneous symptoms. The World Health Organization estimates that the disorder impacts more than 20 million people worldwide. Annual associated costs for schizophrenia are estimated to be more than $150 billion in the United States. As one of the leading causes of disability worldwide, it often results in significant emotional and functional burden for those who experience symptoms, as well as their family and friends. This chronic and disabling mental health condition is thought to result from a complex interplay of genetic and environmental risk factors. Traditional treatment approaches for schizophrenia rely on the use of antipsychotic medications that can lead to considerable short- and long-term health impacts.

About Neurocrine Biosciences

Neurocrine Biosciences is a leading neuroscience-focused, biopharmaceutical company with a simple purpose: to relieve suffering for people with great needs, but few options. We are dedicated to discovering and developing life-changing treatments for patients with under-addressed neurological, neuroendocrine, and neuropsychiatric disorders. The company’s diverse portfolio includes FDA-approved treatments for tardive dyskinesia, chorea associated with Huntington’s disease, endometriosis* and uterine fibroids*, as well as a robust pipeline including multiple compounds in mid- to late-stage 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 (formerly Twitter, and Facebook.

(*in collaboration with AbbVie)

The NEUROCRINE BIOSCIENCES Logo Lockup and YOU DESERVE BRAVE SCIENCE are registered trademarks of Neurocrine Biosciences, Inc.

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 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 press release after the date hereof other than required by law.

Neurocrine Biosciences, Inc.

Media:

Linda Seaton

1-858-617-7292

media@neurocrine.com

Investors:

Todd Tushla

1-858-617-7143

ir@neurocrine.com

# # #

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 Size2 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

Cover	Aug. 28, 2024
Cover [Abstract]
Document Type	8-K
Document Period End Date	Aug. 28, 2024
Entity Registrant Name	NEUROCRINE BIOSCIENCES, INC.
Entity Incorporation, State or Country Code	DE
Entity File Number	0-22705
Entity Tax Identification Number	33-0525145
Entity Address, Address Line One	6027 Edgewood Bend Court
Entity Address, City or Town	San Diego,
Entity Address, State or Province	CA
Entity Address, Postal Zip Code	92130
City Area Code	858
Local Phone Number	617-7600
Title of 12(b) Security	Common Stock, $0.001 par value
Trading Symbol	NBIX
Security Exchange Name	NASDAQ
Written Communications	false
Soliciting Material	false
Pre-commencement Tender Offer	false
Pre-commencement Issuer Tender Offer	false
Entity Emerging Growth Company	false
Amendment Flag	false
Entity Central Index Key	0000914475