What changed in this filing

/stocks — the workspaceLOADING

Item 1. Business

2025-02-10 compared with 2024-02-09 · 114 added, 173 removed, 296 unchanged (49% of the section changed)

1 unchanged sentence

to relieve suffering for people with great needs, but few options.

For three decades, we have applied our unique insight into neuroscience and the interconnections between brain and body systems to advance medicines for the treatment of under-addressed neurological, neuroendocrine and neuropsychiatric disorders and we will continue to relentlessly pursue medicines to ease the burden of debilitating diseases and disorders.

We launched INGREZZA in the U.S.

in May 2017 as the first U.S.

Food and Drug Administration (FDA)-approved drug for the treatment of tardive dyskinesia and in August 2023 for the treatment of chorea associated with Huntington's disease.

INGREZZA provides a once-daily dosing treatment option with a recommended dose of 40 mg taken for the first seven days of treatment for tardive dyskinesia and fourteen days for chorea associated with Huntington’s disease, and an option to take 40 mg, 60 mg, or 80 mg thereafter, depending on the patient’s dosing needs.

In 2023, INGREZZA helped more people affected by tardive dyskinesia than ever before, reflecting higher prescription demand driven by increased commercial activities, including the continued investment in our branded direct-to-consumer INGREZZA advertising campaign and benefit from the expansion of our sales force completed in April 2022.

Going forward, key elements of our commercial strategy include maximizing the opportunity in INGREZZA through consistent and effective commercial execution, continued development of valbenazine as the best-in-class treatment for new patient populations and to lead the evolving understanding of VMAT2 biology and its role in disease.

INGREZZA net product sales totaled $1.8 billion for 2023, $1.4 billion for 2022 and $1.1 billion for 2021 and accounted for approximately 99% of our total net product sales for 2023.

Our internal research and development efforts are focused on innovative therapies with clear and defined clinical and regulatory paths to approval.

From time to time, we supplement our internal research and development efforts by in-licensing the rights to certain clinical development programs or by acquiring businesses that synergize with and allow us to capitalize on our existing development and commercial capabilities.

We are dedicated to discovering and developing life-changing treatments for patients with under-addressed neuropsychiatric, neurological, and neuroendocrine disorders.

Our portfolio of products includes U.S.

Food and Drug Administration (FDA) approved treatments for tardive dyskinesia, chorea associated with Huntington's disease, classic congenital adrenal hyperplasia (CAH), and endometriosis and uterine fibroids in collaboration with AbbVie Inc.

In addition, we have a diversified portfolio of multiple compounds in mid- to late-phase development across our core therapeutic areas and an expanding early-phase pipeline that includes a range of modalities including small molecules, peptides, proteins, antibodies, and gene therapy.

We launched INGREZZA ® (valbenazine) in the U.S.

as the first FDA-approved drug for the treatment of tardive dyskinesia in May 2017 and for the treatment of chorea associated with Huntington's disease in August 2023 and launched CRENESSITY TM (crinecerfont) in the U.S.

as a first-in-class FDA-approved treatment of CAH in December 2024.

We estimate that tardive dyskinesia affects approximately 800,000 people in the U.S., that approximately 90% of the 40,000 people in the U.S.

affected by Huntington’s disease will develop chorea, and that CAH affects approximately 30,000 people in the U.S.

Key elements of our commercial strategy include maximizing the opportunities in INGREZZA and CRENESSITY through consistent and effective commercial execution, continued development of valbenazine as the best-in-class treatment for new patient populations, and to lead the evolving understanding of VMAT2 biology and its role in disease.

INGREZZA net product sales totaled $2.3 billion for 2024, $1.8 billion for 2023, and $1.4 billion for 2022 and accounted for substantially all of our total net product sales during each of these years.

Our partner Mitsubishi Tanabe Pharma Corporation (MTPC) launched DYSVAL ® (valbenazine) in Japan for the treatment of tardive dyskinesia in June 2022 and subsequently in other select Asian markets, where it is marketed as REMLEAS ® (valbenazine).

We receive royalties at tiered percentage rates on MTPC net sales of valbenazine.

Our partner AbbVie launched ORILISSA ® (elagolix tablets) in the U.S.

for the treatment of endometriosis in August 2018 and ORIAHNN ® (elagolix, estradiol and norethindrone acetate capsules and elagolix capsules) in the U.S.

for the treatment of heavy menstrual bleeding due to uterine fibroids in June 2020.

We receive royalties at tiered percentage rates on AbbVie net sales of elagolix.

Commercial Products

2 unchanged sentences

Chorea Associated with Huntington’s Disease

Classic Congenital Adrenal Hyperplasia

Endometriosis U.S.

Uterine Fibroids

Adrenal Insufficiency

2 unchanged sentences

United Kingdom, EU4 (3)

Endometriosis U.S.

Uterine Fibroids

(1) INGREZZA is marketed as DYSVAL ® (valbenazine) in Japan and REMLEAS ® (valbenazine) in other select Asian markets, where Mitsubishi Tanabe Pharma Corporation retains commercialization rights.

(1) INGREZZA is marketed as DYSVAL ® (valbenazine) in Japan and REMLEAS ® (valbenazine) in other select Asian markets, where MTPC retains commercialization rights.

(2) ALKINDI is marketed as ALKINDI SPRINKLE ® (hydrocortisone) in the U.S., where Eton Pharmaceuticals, Inc.

2 unchanged sentences

Germany, France, Italy, and Spain.

(4) AbbVie Inc.

retains global commercialization rights to elagolix.

Marketing and Distribution

(4) AbbVie retains global commercialization rights to elagolix.

Commercial Operations

Our specialty sales force consists of approximately 600 experienced sales professionals located in the U.S.

and is divided into three dedicated sales teams focused on psychiatry, neurology and long-term care.

For INGREZZA, our customers in the U.S.

consist of a limited network of specialty pharmacy providers that deliver INGREZZA to patients by mail, wholesale distributors that distribute INGREZZA primarily to certain specialty pharmacies, and specialty distributors that distribute INGREZZA primarily to closed-door pharmacies and government facilities.

We rely on third-party service providers to perform a variety of functions related to the packaging, storage and distribution of INGREZZA.

and is divided into four dedicated sales teams focused on psychiatry, neurology, long-term care, and rare diseases.

We sell INGREZZA in the U.S.

principally to a limited network of specialty pharmacy providers, wholesale distributors, and specialty distributors.

In addition, we sell CRENESSITY in the U.S.

to a specialty pharmacy provider.

Manufacturing and Supply

We currently rely on, and intend to continue to rely on, third-party manufacturers for the production of INGREZZA and our product candidates.

Raw materials, active pharmaceutical ingredients (API) and other supplies required for the production of INGREZZA and our product candidates are sourced from various third-party manufacturers and suppliers in quantities adequate to meet our needs.

Continuing adequate supply of such raw materials and API is assured through our long-term commercial supply and manufacturing agreements with multiple manufacturers and our continued focus on the expansion and diversification of our third-party manufacturing relationships.

We believe our outsourced manufacturing strategy enables us to direct our financial resources to the maximization of our opportunity with INGREZZA, investment in our internal research and development programs and expansion of our clinical pipeline through business development opportunities.

We currently rely on, and intend to continue to rely on, third-party manufacturers for the production of INGREZZA, CRENESSITY, and our product candidates.

Raw materials, active pharmaceutical ingredients (API), and other supplies required for the production of INGREZZA, CRENESSITY, and our product candidates are sourced from various third-party manufacturers and suppliers in quantities adequate to meet our needs.

Continuing adequate supply of such raw materials and API is assured through long-term commercial supply and manufacturing agreements with multiple manufacturers and a continued focus on the expansion and diversification of our third-party manufacturing relationships.

We believe our outsourced manufacturing strategy enables us to direct our financial resources to the maximization of our opportunity with INGREZZA and CRENESSITY, investment in our internal research and development programs, and expansion of our clinical pipeline through business development opportunities.

Our third-party manufacturers, suppliers and service providers may be subject to routine current Good Manufacturing Practice (cGMP) inspections by the FDA or comparable agencies in other jurisdictions.

1 unchanged sentence

Clinical Development Programs

The following table highlights our current clinical development programs and the current phase of development for such programs.

The following chart summarizes our clinical development programs

_________________________

* Mitsubishi Tanabe Pharma Corporation retains commercialization rights in Japan and other select Asian markets.

† Heptares Therapeutics Limited retains commercialization rights in Japan, where Neurocrine Biosciences retains the right to opt in to a 50:50 profit sharing arrangement upon certain development events.

(1) This program was in-licensed from Heptares Therapeutics Limited.

(2) This program was in-licensed from Idorsia Pharmaceuticals Ltd.

(3) This program was in-licensed from Xenon Pharmaceuticals Inc.

(4) This program was in-licensed from Sanofi S.A.

(5) This program was in-licensed from Takeda Pharmaceutical Company Limited

Neurocrine Biosciences retains global rights unless otherwise noted.

Program Indication

Small Molecule

* Initiating Phase 1 clinical study in the first quarter of 2025

Neuropsychiatry

Valbenazine is a highly selective VMAT2 inhibitor.

2 unchanged sentences

Specifically, dopamine enables neurotransmission among nerve cells that are involved in voluntary and involuntary motor control.

Dyskinetic Cerebral Palsy.

We have ongoing the Journey TM study, a Phase 3 randomized, double-blind, placebo-controlled clinical study to evaluate the efficacy, safety, and tolerability of valbenazine when administered orally once daily as adjunctive treatment in adolescents and adults with schizophrenia who have had an inadequate response to antipsychotics.

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 U.S.

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.

Osavampator (formerly NBI-1065845)

Osavampator is a potential first-in-class alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) positive allosteric modulator (PAM) in development for patients with inadequate response to treatment of major depressive disorder.

We originally acquired the global rights to osavampator in June 2020 as a 50:50 profit-share product from Takeda.

In January 2025, we agreed with Takeda to convert from sharing operating profits and losses with respect to the development and commercialization of osavampator to a royalty-bearing license.

Pursuant to the license, we have exclusive rights to develop and commercialize osavampator for all indications in all territories worldwide, excluding Japan.

In April 2024, we announced positive top-line data from the Phase 2 SAVITRI™ study of osavampator in adults with major depressive disorder.

The Phase 2 dose-finding study met its primary and key secondary endpoints, demonstrating that once-daily, oral administration of NBI-1065845 produced a statistically significant change from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score at both Day 28 (primary, p=0.0159) and Day 56 (secondary, p=0.0016).

We have an ongoing Phase 3, randomized, double-blind, placebo-controlled clinical study to evaluate the efficacy and safety of osavampator in adults with major depressive disorder.

Major depressive disorder is a mental health disorder characterized by a persistently depressed mood, loss of interest, lack of enjoyment in daily activities, poor concentration, and decreased energy.

Major depressive disorder is one of the leading causes of disability.

Approximately 21 million people in the U.S.

live with major depressive disorder.

It is estimated that roughly one-third of people living with major depressive disorder do not respond to available antidepressants.

NBI-1117568 is a first-in-class, orally active, highly selective investigational M4 agonist in development as a potential treatment for schizophrenia.

As a selective M4 orthosteric agonist, NBI-1117568 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.

Muscarinic receptors are central to brain function and validated as drug targets in psychosis and cognitive disorders.

We acquired the global rights to NBI-1117568, excluding in Japan, from Nxera in 2021.

In August 2024, we announced positive top-line data from the Phase 2 clinical study of NBI-1117568 in adults with schizophrenia.

The Phase 2 dose-finding study met its primary endpoint for the once-daily 20 mg dose, demonstrating a clinically meaningful and statistically significant reduction from baseline in the Positive and Negative Syndrome Scale (PANSS) total score at Week 6 (p=0.011 and effect size of 0.61).

The once-daily 20 mg dose also demonstrated 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.

We expect to advance NBI-1117568 into Phase 3 development in the first half of 2025.

NBI-1070770 is a novel, selective, and orally active, negative allosteric modulator (NAM) of the NR2B subunit-containing N-methyl-D-aspartate (NMDA NR2B) receptor in development as a potential treatment for major depressive disorder.

We acquired the global rights to NBI-1070770 from Takeda in 2020.

We have an ongoing Phase 2, multi-center, randomized, double-blind, placebo-controlled clinical study to evaluate the efficacy, safety, and tolerability of NBI-1070770 in adults with major depressive disorder.

Other Early-Stage Neuropsychiatry Programs

We have ongoing Phase 1 first-in-human clinical studies to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of investigational compounds NBI-1117570, NBI-1117567, NBI-1117569, and NBI-1065890 in healthy adult participants.

NBI-1117570, NBI-1117567 (M1 preferring), and NBI-1117569 (M4 preferring) are investigational, oral, muscarinic M1/M4 agonists being developed for the potential treatment of certain neuropsychiatric and neurological conditions.

We acquired the global rights NBI-1117570, NBI-1117567, and NBI-1117569 from Nxera in 2021.

NBI-1065890 is an investigational, oral, selective VMAT2 inhibitor for the potential treatment of certain neuropsychiatric and neurological conditions.

NBI-1065890 was discovered and is being developed internally at Neurocrine Biosciences.

We have an ongoing Phase 3 randomized, double-blind, placebo-controlled clinical study to evaluate the efficacy, safety, and tolerability of valbenazine for the treatment of dyskinetic cerebral palsy in pediatrics and adults.

Dyskinetic cerebral palsy is a non-progressive, permanent disorder marked by involuntary movement and is a result of damage to the fetal or infant brain’s basal ganglia.

4 unchanged sentences

Dyskinetic cerebral palsy affects up to 15% of the estimated 500,000 to 1 million people affected by cerebral palsy in the U.S.

NBI-921352 is a potent, highly selective Nav1.6 sodium channel inhibitor being developed to treat pediatric patients with SCN8A-DEE and other potential indications.

We acquired the global rights to NBI-921352 in December 2019.

SCN8A Developmental and Epileptic Encephalopathy Syndrome, or SCN8A-DEE.

SCN8A-DEE is a rare, extremely severe, single-gene epilepsy caused by mutations in the SCN8A gene that activates Nav1.6, the most highly expressed sodium channel in the excitatory pathways of the central nervous system.

Children born with SCN8A-DEE typically start experiencing seizures between birth and 18 months of age, and most have multiple seizures per day.

Other symptoms include learning difficulties, muscle spasms, low or high muscle tone, poor coordination, developmental delay and features similar to autism.

As SCN8a mutations were discovered only recently, prevalence estimates will be determined in the future as awareness of and access to genetic surveillance increases.

NBI-921352 has been granted orphan drug and rare pediatric disease designations for the treatment of SCN8A-DEE in the U.S.

Valbenazine in Pediatrics and Adults with Dyskinetic Cerebral Palsy.

We have an ongoing Phase 3 randomized, double-blind, placebo-controlled clinical study to evaluate the efficacy, safety and tolerability of valbenazine for the treatment of dyskinetic cerebral palsy in pediatrics and adults (aged 6 to 70 years).

NBI-921352 in Pediatrics and Adolescents with SCN8A-DEE.

We have ongoing the KAYAK TM study, a Phase 2 randomized, double-blind, placebo-controlled clinical study to evaluate the efficacy, safety and pharmacokinetics of NBI-921352 as adjunctive therapy for seizures in adolescents (aged 12 to 21 years) with SCN8A-DEE.

In January 2022, the study protocol was amended to include pediatrics (aged 2 to 11 years) with SCN8A-DEE.

Neuroendocrinology

Program Indication

Crinecerfont.

Crinecerfont is an investigational, oral, selective corticotropin-releasing factor type 1 (CRF1) receptor antagonist being developed to reduce and control excess adrenal androgens through a steroid-independent mechanism for the treatment of classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD).

Crinecerfont has received orphan drug designation in the U.S.

from the FDA and in the European Union (EU) from the European Medicines Agency (EMA).

Crinecerfont has also received Breakthrough Therapy designation in the U.S.

from the FDA for the treatment of CAH due to 21-OHD in adults and pediatrics.

Classic Congenital Adrenal Hyperplasia.

CAH is a genetic disorder that causes little to no cortisol production and increased secretion of adrenocorticotropic hormone (ACTH) and androgens.

In approximately 75% of cases, the adrenal glands cannot produce aldosterone, which can result in salt wasting adrenal crisis, causing extreme weakness, low blood pressure, shock, and even death.

There are currently no non-steroidal FDA-approved treatments for CAH.

CAH affects up to an estimated 30,000 people in the U.S.

and 50,000 people in Europe.

EFMODY is a modified-release preparation of hydrocortisone that mimics the physiological circadian rhythm of cortisol and has been specifically designed for patients with diseases of cortisol deficiency, such as CAH and adrenal insufficiency.

Classic Congenital Adrenal Hyperplasia.

Adrenal Insufficiency.

Adrenal insufficiency is a rare condition caused by inadequate production of steroid hormones in the cortex of the adrenal glands.

Adrenal insufficiency can result in severe fatigue and, if left untreated, adrenal crisis that may be life threatening.

Crinecerfont in Adults with CAH.

In September 2023, we announced positive top-line data from the Phase 3 CAHtalyst™ clinical study of crinecerfont in adults with CAH due to 21-OHD.

The Phase 3 adult study met its primary endpoint at Week 24, demonstrating that treatment with crinecerfont resulted in a statistically significant percent reduction in daily glucocorticoid (GC) dose versus placebo while maintaining androgen control (p-value <0.0001).

The study also met important key secondary endpoints, with a statistically significant decrease in androstenedione at Week 4 versus placebo (p-value <0.0001).

At Week 24, approximately 63% of patients on crinecerfont achieved a reduction to a physiologic GC dose versus approximately 18% on placebo (p-value <0.0001).

The data from the Phase 3 adult study, including data from the open-label treatment period, will support New Drug Application (NDA) submission to the FDA in the second quarter of 2024.

Crinecerfont in Pediatrics with CAH.

In October 2023, we announced positive top-line data from the Phase 3 CAHtalyst™ clinical study of crinecerfont in pediatrics (aged 2 to 17 years) with CAH due to 21-OHD.

The Phase 3 pediatric study met its primary endpoint, demonstrating that treatment with crinecerfont resulted in a statistically significant decrease in serum androstenedione from baseline at Week 4 versus placebo following a GC stable period (p = 0.0002).

Consistent with the results from the Phase 3 adult study, crinecerfont treatment led to a statistically significant percent reduction from baseline in daily GC dose while maintaining androgen control at Week 28 versus placebo (p < 0.0001).

Approximately 30% of participants receiving crinecerfont achieved a reduction to a physiologic GC dose while maintaining androgen control compared to 0% of participants receiving placebo.

The study also met the other key secondary endpoint demonstrating a statistically significant decrease in serum 17-hydroxyprogesterone from baseline at Week 4 versus placebo (p < 0.0001).

The data from the Phase 3 pediatric study, including data from the open-label treatment period, will support NDA submission to the FDA in the second quarter of 2024.

EFMODY in Adolescents and Adults with CAH.

We have an ongoing Phase 2 randomized, double-blind, active-controlled clinical study to evaluate the efficacy, safety and tolerability of twice-daily EFMODY compared with twice-daily Cortef ® (immediate-release hydrocortisone tablets) in adolescents and adults (aged 16 years and older) with CAH.

We anticipate having top-line data for this clinical study in the first half of 2024.

EFMODY in Adults with Adrenal Insufficiency.

We have ongoing the CHAMPAIN study, a Phase 2 randomized, double-blind, double-dummy, two-way crossover clinical study to evaluate the efficacy, safety and tolerability of twice-daily EFMODY compared with once-daily Plenadren ® (modified-release hydrocortisone tablets) in adults with primary adrenal insufficiency.

We anticipate having top-line data for this clinical study in the first half of 2024.

Neuropsychiatry

Program Indication

Valbenazine is a highly selective VMAT2 inhibitor.

VMAT2 is a protein concentrated in the human brain that is essential for the transmission of nerve impulses between neurons.

VMAT2 is primarily responsible for packaging and transporting monoamines (dopamine, norepinephrine, serotonin and histamine) in neurons.

Specifically, dopamine enables neurotransmission among nerve cells that are involved in voluntary and involuntary motor control.

Schizophrenia.

Schizophrenia is a spectrum of serious neuropsychiatric brain diseases in which people interpret reality abnormally.

Schizophrenia may result in some combination of hallucinations, delusions and extremely disordered thinking and behavior that impairs daily life.

People with schizophrenia typically require lifelong treatment.

Early treatment may help improve long-term prognosis and get symptoms under control before serious complications develop.

Schizophrenia affects an estimated 3.5 million people in the U.S.

All currently approved antipsychotic medications are believed to work through direct action on monoaminergic receptors, with approximately 40% of patients reporting negative side effects and approximately 30% not benefiting adequately from these medications.

NBI-1117568 is a potential first-in-class muscarinic M4 receptor agonist with the potential to be developed for the treatment of schizophrenia.

As a selective M4 orthosteric agonist, NBI-1117568 offers the potential for an improved safety profile without the need for combination therapy to ameliorate off-target effects or for cooperativity with acetylcholine.

Muscarinic receptors are central to brain function and validated as drug targets in psychosis and cognitive disorders.

We acquired the global rights to NBI-1117568 in December 2021.

Luvadaxistat.

Luvadaxistat is a potential first-in-class D-Amino Acid Oxidase (DAAO) inhibitor with the potential to be developed for the treatment of cognitive impairment associated with schizophrenia.

We acquired the global rights to luvadaxistat in June 2020.

Cognitive Impairment Associated with Schizophrenia, or CIAS.

CIAS, which may include deficits in attention, working memory and executive function, has a negative impact on patients’ quality of life and ability to function.

Although cognitive symptoms in schizophrenia are well characterized, no formal diagnostic criteria exist.

Furthermore, no pharmacological agents are approved to treat the condition, and no marketed therapy tested to date has established clear, meaningful efficacy, which underscores the difficulty of drug development in this arena and accentuates the unmet need for proven treatment options.

Approximately 80% of the estimated 3.5 million people affected by schizophrenia in the U.S.

experience clinically relevant cognitive impairment.

NBI-1065845 is a potential first-in-class Alpha-Amino-3-Hydroxy-5-Methyl-4-Isoxazole Propionic Acid (AMPA) potentiator with the potential to be developed for the treatment of inadequate response to treatment in major depressive disorder.

We acquired the global rights to NBI-1065845 in June 2020.

NBI-1065845 is currently designated as a 50:50 profit-share product with Takeda Pharmaceutical Company Limited, which retains a one-time opt-out right to convert the designation to a royalty-bearing product.

Major Depressive Disorder.

Major depressive disorder is one of the leading causes of disability and is characterized by a persistently depressed mood or loss of interest in daily activities that is present most of the day in addition to other symptoms that can impact normal daily functioning, relationships and overall quality of life.

Treatments range from selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, atypical antipsychotics, tricyclic antidepressants and psychotherapies, among others.

Approximately 30% of the more than 16 million people affected by the disorder in the U.S.

do not adequately respond to treatment.

Valbenazine in Adolescents and Adults with Schizophrenia.

We have an ongoing Phase 3 randomized, double-blind, placebo-controlled clinical study to evaluate the efficacy, safety and tolerability of valbenazine when administered orally once daily as adjunctive treatment in adolescents and adults (aged 13 years and older) with schizophrenia who have had an inadequate response to antipsychotics.

NBI-1117568 in Adults with Schizophrenia.

We have an ongoing Phase 2 multi-center, randomized, double-blind, placebo-controlled, multi-arm, multi-stage clinical study to evaluate the efficacy, safety and tolerability of NBI-1117568 in adults with schizophrenia who are experiencing an acute exacerbation or relapse of symptoms.

We anticipate having top-line data for this clinical study in the second half of 2024.

Luvadaxistat in Adults with CIAS.

We have ongoing the ERUDITE™ study, a Phase 2 randomized, double-blind, parallel, placebo-controlled clinical study to evaluate the efficacy, safety, tolerability and pharmacokinetics of luvadaxistat when administered orally once daily as adjunctive treatment in adults with CIAS.

We anticipate having top-line data for this clinical study in the second half of 2024.

NBI-1065845 in Adults with Inadequate Response to Treatment in Major Depressive Disorder.

We have ongoing the SAVITRI™ study, a Phase 2 randomized, double-blind, placebo-controlled clinical study to evaluate the efficacy and safety of NBI-1065845 as adjunctive treatment in adults with inadequate response to treatment in major depressive disorder.

We anticipate having top-line data for this clinical study in the first half of 2024.

NBI-1076986 is an investigational, oral, muscarinic M4 selective acetylcholine antagonist for the potential treatment of certain movement disorders.

NBI-1076986 was discovered and is being developed internally at Neurocrine Biosciences.

We have an ongoing Phase 1 first-in-human clinical study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of investigational compound NBI-1076986 in healthy adult participants.

Intellectual Property

5 unchanged sentences

Below is a description of the U.S.

patents to INGREZZA and crinecerfont:

patents to INGREZZA and CRENESSITY:

• INGREZZA, our highly selective VMAT2 inhibitor approved in the U.S.

3 unchanged sentences

8,039,627, which now expires in 2031 and covers valbenazine, the active pharmaceutical ingredient contained in INGREZZA.

In Japan and in certain other East Asian markets, we are actively pursuing most of the patents corresponding to those listed in the FDA’s Orange Book entry for INGREZZA.

In 2023, we entered into settlement agreements resolving all patent litigation brought by us against the companies that filed ANDAs seeking approval to market generic versions of INGREZZA, and all cases have been dismissed.

1 unchanged sentence

beginning March 1, 2038, or earlier under certain circumstances.

Refer to Note 13 to the consolidated financial statements for a more detailed description of these matters.

• Crinecerfont, a CRF1 receptor antagonist under clinical development for the treatment of CAH in adults and children, is covered by U.S.

10,905,690, 11,311,544, and 11,730,739, among other patents and pending patent applications, set to expire between 2035 and 2044 (not including any potential patent term extensions).

• CRENESSITY, a CRF1 receptor antagonist approved in the U.S.

for the treatment of CAH in adults and children, is covered by U.S.

patents among other patents set to expire between 2035 and 2041 (not including any potential patent term extensions), and pending patent applications, which, if issued, could expire at least as late as 2045.

We also own, or have licensed rights to, patents covering our other products and earlier stage product candidates.

2 unchanged sentences

If this protection is available, no competitor may use the original applicant’s data as the basis of a generic marketing application during the period of data and marketing exclusivity, which is measured from the date of marketing approval by the FDA or corresponding foreign regulatory authority.

This period of exclusivity is generally five years in the U.S., six years in Japan and 10 years in the EU, except that for biologics, the period of exclusivity in the U.S.

This period of exclusivity is generally five years in the U.S., six years in Japan and eight years in the EU, with marketing exclusivity lasting an additional two years in the EU, except that for biologics, the period of exclusivity in the U.S.

is 12 years under the Biologics Price Competition and Innovation Act.

5 unchanged sentences

We face, and will continue to face, competition in the development and marketing of our products and product candidates from academic institutions, government agencies, research institutions and biotechnology and pharmaceutical companies.

Many of our competitors have significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approval and marketing than we do.

Competition may also arise from, among other things, other drug development technologies, methods of preventing or reducing the incidence of disease, including vaccines, and new small molecule or other classes of therapeutic agents.

4 unchanged sentences

In addition, there are several programs in clinical development by other companies targeting Huntington's disease.

• ORILISSA and ORIAHNN each compete with several FDA-approved products for the treatment of endometriosis, uterine fibroids, infertility and central precocious puberty.

Additionally, there is also competition from surgical intervention, including hysterectomies and ablations.

Separate from these options, there are many programs in clinical development which serve as potential future competition.

Lastly, there are numerous medicines used to treat the symptoms of disease (vs.

endometriosis or uterine fibroids directly) which may also serve as competition:

oral contraceptives, NSAIDs and other pain medications, including opioids.

• For CAH, high doses of corticosteroids are the current standard of care to both correct the endogenous cortisol deficiency as well as reduce the excessive ACTH levels.

• CRENESSITY competes with high dose corticosteroid monotherapy which is the current standard of care to both correct the endogenous cortisol deficiency as well as reduce the excessive adrenocorticotropic hormone levels for patients with CAH.

alone, there are more than two dozen companies manufacturing steroid-based products.

In addition, there are several programs in clinical development by other companies targeting CAH with a variety of approaches including gene therapy.

• Our investigational treatments for potential use in epilepsy may in the future compete with numerous approved anti-seizure medications and development-stage programs being pursued by several other companies.

Commonly used anti-seizure medications include phenytoin, levetiracetam, brivaracetam, cenobamate, carbamazepine, clobazam, lamotrigine, valproate, oxcarbazepine, topiramate, lacosamide, perampanel and cannabidiol, among others.

There are currently no FDA-approved treatments specifically indicated for the early infantile epileptic encephalopathy SCN8A-DEE;

however, a number of different anti-seizure medications are currently used in these patient populations.

• Our investigational treatments for potential use in schizophrenia, anhedonia and depression may in the future compete with several development-stage programs being pursued by other companies.

Currently, there are no FDA-approved treatments specifically indicated for anhedonia or CIAS;

however, there are a number of different anti-psychotic medications currently used in these patient populations.

In addition, there are several programs in clinical development by other companies targeting CAH.

• Our investigational treatments for potential use in schizophrenia and depression may in the future compete with several development-stage programs being pursued by other companies.

In addition, there are a number of different anti-psychotic and anti-depressant medications currently used in these patient populations.

• Our investigational treatments for potential use in neurology, neuroendocrinology and neuropsychiatry may in the future compete with numerous approved products and development-stage programs being pursued by several other companies.

128 unchanged sentences

In the U.S., the pharmaceutical industry and the cost of prescription drugs has been a continuous focus of these efforts and has been significantly affected by major legislative initiatives.

Most recently, in August 2022, President Biden signed into law the Inflation Reduction Act of 2022 (IRA), which, among other things, (1) directs the Secretary of the U.S.

Most recently, in August 2022, the Inflation Reduction Act of 2022 (IRA) was signed into law, which, among other things, (1) directs the Secretary of the U.S.

Department of Health and Human Services (HHS) to negotiate the price of certain high-expenditure, single-source drugs and biologics covered under Medicare, (2) redesigns the Medicare Part D prescription drug benefit to lower patient out-of-pocket costs and increase manufacturer liability and (3) requires drug manufacturers to pay rebates on drugs whose prices increase greater than the rate of inflation.

The IRA also extends enhanced subsidies for individuals purchasing health insurance coverage in the ACA marketplaces through plan year 2025 and eliminates the “donut hole” under the Medicare Part D program beginning in 2025 by significantly lowering the beneficiary maximum out-of-pocket cost to $2,000 through a newly established manufacturer discount program.

These provisions take effect progressively starting in 2023.

On August 29, 2023, HHS announced the list of the first 10 drugs that will be subject to price negotiations, although the Medicare drug price negotiation program is currently subject to legal challenges.

It is currently unclear how the IRA will be implemented;

however, it is likely to have a significant impact on the pharmaceutical industry and prescription drug pricing.

While the IRA targets high-expenditure drugs that have been on the market for several years without generic or biosimilar competition, we expect to qualify for the small biotech manufacturer exemption that is set to expire in 2029.

However, the qualification for this exemption is subject to various requirements and there is no assurance that we will continue to qualify for this exemption in the future.

Further, the loss of this exemption or the potential loss of this exemption, including as a result of a potential acquisition or strategic transaction, could have an adverse impact on our business.

The IRA also extends enhanced subsidies for individuals purchasing health insurance coverage in the ACA marketplaces through plan year 2025 and eliminated the “donut hole” under the Medicare Part D program in 2025 by significantly lowering the beneficiary maximum out-of-pocket cost to $2,000 through a newly established manufacturer discount program.

These provisions took effect progressively starting in 2023.

On August 15, 2024, HHS announced the negotiated prices of the first 10 drugs that were subject to price negotiations, although the Medicare drug price negotiation program is currently subject to legal challenges.

On January 17, 2025, HHS announced its selection of fifteen additional drugs covered under Part D for negotiation in 2025 (for initial price applicability year 2027).

Certain high-expenditure Part B and Part D drugs/biologics will be selected for negotiation in 2026 (for initial price applicability year 2028) and annually thereafter.

AUSTEDO and AUSTEDO XR, marketed by Teva Pharmaceuticals Industries, have been selected for the Medicare drug negotiation program in 2025 (for initial price applicability year 2027).

If the negotiation program results in a decrease in the price of AUSTEDO or AUSTEDO XR, it may result in increased competitive pressure on INGREZZA.

The overall impact of any potential negotiated priced reduction of AUSTEDO or AUSTEDO XR on INGREZZA revenues is inherently uncertain and difficult to predict.

While the Medicare drug negotiation program targets high-expenditure drugs/biologics that have been on the market for several years without generic or biosimilar competition, we were notified in January 2025 that INGREZZA qualifies for the small biotech exception, which provides an exemption from selection for price negotiation until 2027 (for initial price applicability year 2029, pursuant to which negotiated pricing would go into effect, if selected).

Additionally, on January 1, 2025, the Centers for Medicare & Medicaid Services (CMS) implemented those provisions of the IRA establishing a new Medicare Part D manufacturer discount program.

Under this discount program and subject to certain exceptions, manufacturers must give a 10 percent discount on Part D program drugs in the initial coverage phase, and a 20 percent discount on Part D drugs when the beneficiary enters the catastrophic coverage phase (the phase after the patient incurs costs above the initial phase out-of-pocket threshold, which is $2,000).

However, the IRA allows the 10 and 20 percent discounts to be phased in over a multi-year period for “specified manufacturers” and “specified small manufacturers”.

During this phase-in period, such manufacturers would pay a lower percentage discount on Medicare Part D program drugs.

In April 2024, the Company was notified by CMS that it qualified as a “specified small manufacturer” and will receive the discount phase-in discussed above for INGREZZA.

INGREZZA is reimbursed under Medicare Part D, and increased discounts could impact INGREZZA revenues, while also having an industry-wide impact on the cost of other Part D program drugs such as AUSTEDO and AUSTEDO XR.

The overall impact on INGREZZA revenues is inherently uncertain and difficult to predict and we are still evaluating the potential impact of this discount program and our designation as a “specified small manufacturer.”

Our designation as a “specified small manufacturer” under the new Medicare Part D manufacturer discount program and INGREZZA’s qualification for the small biotech exception for purposes of the Medicare drug price negotiation program are subject to various requirements and there is no assurance that we will continue to qualify for these exemptions in the future.

The loss or potential loss of these exemptions, including as a result of a third party acquiring us, could have an adverse impact on our business.

The most significant prior revisions to federal law governing the pharmaceutical industry and prescription drug pricing were enacted through the March 2010 Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act (collectively, the ACA).

6 unchanged sentences

For example, on January 5, 2024, the FDA approved Florida’s Section 804 Importation Program (SIP) proposal to import certain drugs from Canada for specific state healthcare programs.

It is unclear how this program will be implemented, including which drugs will be chosen, and whether it will be subject to legal challenges in the United States or Canada.

It is unclear how this program will be implemented, including which drugs will be chosen, and whether it will be subject to legal challenges in the U.S.

Other states have also submitted SIP proposals that are pending review by the FDA.

8 unchanged sentences

In the U.S., the pharmaceutical industry has been a particular focus of these efforts and may be significantly affected by major legislative initiatives.

We are currently unable to predict what other additional legislation or regulation, if any, relating to the healthcare industry may be enacted in the future or what effect recently enacted federal legislation or any such additional legislation or regulation would have on our business.

Presidential and Congressional elections.

Regulation and Procedures Governing Approval of Medicinal Products in the EU

7 unchanged sentences

Clinical Trials in the EU

In the EU, the Clinical Trials Regulation (EU) No 536/2014 (CTR) entered into application on January 31, 2022 repealing and replacing the former Clinical Trials Directive 2001/20 (CTD).

In the EU, the Clinical Trials Regulation (EU) No 536/2014 (CTR) entered into application on January 31, 2022 and became effective for all clinical trials on January 31, 2025, repealing and replacing the former Clinical Trials Directive 2001/20 (CTD).

The regulation introduces a streamlined application procedure via a single entry point, the “EU portal”, the Clinical Trials Information System (CTIS);

1 unchanged sentence

A harmonized procedure for the assessment of applications for clinical trials has been introduced and is divided into two parts.

The extent to which on-going clinical trials will be governed by the CTR will depend on the duration of the individual clinical trial.

For clinical trials in relation to which an application for approval was made on the basis of the CTD before January 31, 2023, the CTD will continue to apply on a transitional basis until January 31, 2025.

By that date, all ongoing trials will become subject to the provisions of the CTR.

The CTR will apply to clinical trials from an earlier date if the related clinical trial application was made on the basis of the CTR or if the clinical trial has already transitioned to the CTR framework before January 31, 2025.

Marketing Authorizations

49 unchanged sentences

Our Employees

We have grown to a team of more than 1,400 employees as of December 31, 2023, primarily employed in the U.S.

We have grown to a team of approximately 1,800 employees as of December 31, 2024, primarily employed in the U.S.

Our highly qualified and experienced team, which includes scientists, physicians, and professionals across sales, marketing, manufacturing, regulatory, finance, and other essential functions are critical to our success.

We also leverage temporary workers to provide flexibility for our business needs.

During 2023, we added approximately 200 new employees to our team.

During 2024, we added more than 400 new employees to our team.

We expect to add additional employees in 2025 with a focus on expanding our research and development organization.

2 unchanged sentences

The success of our human capital management investments is evidenced by our low employee turnover, a number which is regularly reviewed by our Board of Directors as part of their oversight of our human capital strategy.

In recognition of our efforts, in 2023, we were ranked #8 in Fortune Best Workplaces in Biopharma TM .

In recognition of our efforts, in 2024, we were ranked #7 in Fortune Best Workplaces in Biopharma TM and named Company of the Year:

Specialty Pharma/Biotech in the PM360 Trailblazer Awards.

Employee Engagement, Talent Development & Benefits

9 unchanged sentences

We were originally incorporated in California in January 1992 and reincorporated in Delaware in May 1996.

Our principal executive offices are located at 12780 El Camino Real, San Diego, California 92130.

Our principal executive offices are located at 6027 Edgewood Bend Court, San Diego, California 92130.

Our telephone number is (858) 617-7600.

3 unchanged sentences

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business