NBI-1117568 / Nxera Pharma, Neurocrine Biosciences - LARVOL DELTA

An Assessment of Efficacy, Safety, and Pharmacokinetics of NBI-1117568 in Adults With Bipolar I Disorder With Current Mania (clinicaltrials.gov) - P2 | N=150 | Recruiting | Sponsor: Neurocrine Biosciences | Not yet recruiting ➔ Recruiting

Enrollment open • Bipolar Disorder • CNS Disorders • Mood Disorders • Psychiatry

NBI-1117568-SCZ3030: Evaluation of NBI-1117568 in Inpatient Adults with Schizophrenia (clinicaltrialsregister.eu) - P2/3 | N=141 | Recruiting | Sponsor: Neurocrine Biosciences Inc.

New P2/3 trial • CNS Disorders • Psychiatry • Schizophrenia

NBI-1117568-SCZ3032: Long-Term Safety and Tolerability of NBI-1117568 in Adults with Schizophrenia (clinicaltrialsregister.eu) - P2/3 | N=151 | Recruiting | Sponsor: Neurocrine Biosciences Inc.

New P2/3 trial • CNS Disorders • Psychiatry • Schizophrenia

New Pharmacological Treatment Approaches for Schizophrenia: Navigating the Post-iclepertin Landscape. (PubMed, CNS Drugs) - "The most compelling therapeutic approaches continue to be serotonin-dopamine activity modulators (brilaroxazine) and emerging M4 selective agonists (NBI-1117568). While iclepertin's discontinuation represents a significant setback for GlyT1 inhibition strategies, the approval of KarXT and advancing pipeline candidates offer potential for therapeutic advances. Critical challenges include escalating placebo responses that compromise trial assay sensitivity, underscoring the need for improved patient stratification, refined trial methodology, and outcome measures that accurately capture real-world benefit."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Mental Retardation • Psychiatry • Schizophrenia • DRD2

An Assessment of Efficacy, Safety, and Pharmacokinetics of NBI-1117568 in Adults With Bipolar I Disorder With Current Mania (clinicaltrials.gov) - P2 | N=150 | Not yet recruiting | Sponsor: Neurocrine Biosciences

New P2 trial • Bipolar Disorder • CNS Disorders • Mood Disorders • Psychiatry

Efficacy of NBI-1117568 in Preventing Relapse in Adults With Schizophrenia (clinicaltrials.gov) - P3 | N=560 | Not yet recruiting | Sponsor: Neurocrine Biosciences

New P3 trial • CNS Disorders • Psychiatry • Schizophrenia

Receptor subtype specific modulation of muscarinic pathways: a mechanistically distinct therapeutic strategy for schizophrenia (ECNP 2025) - "VU0152100, a selective M4 PAM, exhibits antipsychotic-like effects in rodent models, reducing amphetamine induced locomotor hyperactivity and reversing behavioral deficits...NBI-1117568, a selective M4 orthosteric agonist in Phase 2 trials for schizophrenia, attenuates dopaminergic hyperactivity and restores sensorimotor gating without sedative or motor impairments. Blarcamesine has shown neuroprotective and cognitive enhancing effects in multiple models... Targeting mAChRs, particularly M1 and M4, provides a receptor subtype specific strategy to address unmet needs in schizophrenia. KarXT and emraclidine represent leading agents in clinical development. Emerging modulators such as BQCA, AC-42, and the VU series highlight the diversity of mechanisms and potential for precision treatment tailored to receptor expression profiles and schizophrenia endophenotypes [3]."

CNS Disorders • Psychiatry • Schizophrenia

NBI-1117568-SCZ3030: Evaluation of NBI-1117568 in Inpatient Adults With Schizophrenia (clinicaltrials.gov) - P3 | N=284 | Recruiting | Sponsor: Neurocrine Biosciences | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Psychiatry • Schizophrenia

Nxera Pharma Operational Highlights and Consolidated Results for the Second Quarter and First Half 2025 (The Manila Times) - "Progress with partnered programs: Neurocrine Biosciences dosed the first patient in its Phase 3 registrational program of NBI-1117568 (NBI-‘568), resulting in a payment of US$15 million to the Company....The Phase 3 study is a global double-blind, placebo-controlled trial evaluating NBI-’568 in adults with a primary diagnosis of schizophrenia who are experiencing an acute exacerbation or relapse of symptoms. The study is expected to enroll approximately 280 patients."

Financing • Trial status • Schizophrenia

NBI-1117568-SCZ3032: Long-Term Evaluation of NBI-1117568 in Adults With Schizophrenia (clinicaltrials.gov) - P3 | N=800 | Recruiting | Sponsor: Neurocrine Biosciences

New P3 trial • CNS Disorders • Psychiatry • Schizophrenia

NBI-1117568-SCZ3030: Evaluation of NBI-1117568 in Inpatient Adults With Schizophrenia (clinicaltrials.gov) - P3 | N=284 | Not yet recruiting | Sponsor: Neurocrine Biosciences

New P3 trial • CNS Disorders • Psychiatry • Schizophrenia

Neurocrine Biosciences Presents New Positive Data from Phase 2 Study of NBI-1117568 in Adults with Schizophrenia at American Society of Clinical Psychopharmacology 2025 (PRNewswire) - P2 | N=210 | NCT05545111 | Sponsor: Neurocrine Biosciences | "Neurocrine Biosciences...announced the presentation of data from the Phase 2 study of NBI-1117568 in adults with schizophrenia, which showed a significant improvement in symptoms and overall severity and highlighted new data on the safety and tolerability of the treatment...These results were shared as an oral presentation and poster at the American Society of Clinical Psychopharmacology 2025 Annual Meeting in Scottsdale, Arizona....The primary endpoint was the change in total Positive and Negative Syndrome Scale (PANSS) score from baseline to Week 6. The study showed statistically significant improvements in PANSS total score with 20 mg of NBI-1117568 once daily by Week 3 and at all subsequent visits through Week 6. A statistically significant improvement was also observed by Week 2 in the Clinical Global Impression of Severity (CGI-S) scale, with continued improvement seen at all following visits through Week 6."

P2 data • Schizophrenia

NBI-1117568-SCZ3029: Evaluation of NBI-1117568 in Inpatient Adults With Schizophrenia (clinicaltrials.gov) - P3 | N=284 | Recruiting | Sponsor: Neurocrine Biosciences | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Psychiatry • Schizophrenia

NBI-1117568-SCZ3029: Evaluation of NBI-1117568 in Inpatient Adults With Schizophrenia (clinicaltrials.gov) - P3 | N=284 | Not yet recruiting | Sponsor: Neurocrine Biosciences

New P3 trial • CNS Disorders • Psychiatry • Schizophrenia

Nxera Pharma Operational Highlights and Consolidated Results for the First Quarter 2025 (GlobeNewswire) - "Neurocrine Biosciences, Inc. outlined clinical development plans for the partnered muscarinic agonist portfolio in 2025, including Initiation of Phase 3 registrational studies with NBI-1117568 (an oral, muscarinic M4-selective agonist) in schizophrenia in 1H 2025; Initiation of a Phase 2 study with NBI-1117568 in bipolar mania in 2H 2025; Initiation of a Phase 2 study with NBI-1117570 (a dual M1 / M4 agonist) in schizophrenia in 2H 2025; Data readouts for NBI-1117570, NBI-1117567 (M1-preferring), and NBI-1117569 (M4-preferring) expected in 2025, all of which are being advanced in Phase 1 trials targeting neurological and neuropsychiatric conditions."

Clinical data • New P2 trial • New P3 trial • CNS Disorders • Schizophrenia

Nxera Pharma’s Partner Neurocrine Biosciences Initiates Phase 3 Registrational Program of NBI-1117568 as a Potential Treatment for Adults with Schizophrenia (GlobeNewswire) - "Nxera Pharma...announces that its partner Neurocrine Biosciences Inc. ('Neurocrine') has initiated a Phase 3 registrational program to evaluate the efficacy, safety and tolerability of NBI-1117568 (NBI-’568), an investigational oral muscarinic M4 selective orthosteric agonist, as a potential treatment for schizophrenia....The Phase 3 study is a global double-blind, placebo-controlled trial evaluating NBI-’568 in adults with a primary diagnosis of schizophrenia who are experiencing an acute exacerbation or relapse of symptoms. The study is expected to enroll approximately 280 patients."

Trial status • Schizophrenia

Nxera Pharma Operational Highlights and Consolidated Results for the Fourth Quarter and Full Year 2024 (GlobeNewswire) - "NBI-1117568 (an oral, muscarinic M4-selective agonist): End of Phase 2 meeting with the US Food & Drug Administration completed and reiteration of plans to begin Phase 3 studies in schizophrenia in 1H 2025. Initiate Phase 2 study in bipolar mania in 2H 2025....NBI-1117570 (a dual M1 / M4 agonist): Initiate Phase 2 study in schizophrenia in 2H 2025....NBI-1117567 (an M1-preferring agonist) and NBI-1117569 (an M4-preferring agonist): Phase 1 trials underway targeting neurological and neuropsychiatric conditions with data readouts anticipated during 2025."

FDA event • New P2 trial • New P3 trial • P1 data • Bipolar Disorder • CNS Disorders • Schizophrenia

NBI-1117568-SCZ2028: Efficacy, Safety, Tolerability, and Pharmacokinetics of NBI-1117568 in Adults With Schizophrenia (clinicaltrials.gov) - P2 | N=210 | Completed | Sponsor: Neurocrine Biosciences | Recruiting ➔ Completed | Trial completion date: Dec 2024 ➔ Jul 2024

Trial completion • Trial completion date • CNS Disorders • Psychiatry • Schizophrenia

Neurocrine Biosciences Provides Update on ERUDITE Phase 2 Data for Luvadaxistat in Adults with Cognitive Impairment Associated with Schizophrenia (PRNewswire) - P2 | N=216 | ERUDITE (NCT05182476) | Sponsor: Neurocrine Biosciences | "Neurocrine Biosciences, Inc...today announced that its ERUDITE Phase 2 clinical study of investigational compound luvadaxistat (NBI-1065844) failed to meet its primary endpoint as a potential treatment to improve cognitive impairment in patients with schizophrenia....The ERUDITE study was the second Phase 2 trial for luvadaxistat. It failed to replicate the cognitive endpoints data seen in the earlier INTERACT study, due in part to the large variability seen in the cognitive measures across the population studied and a potential imbalance in the baseline characteristics of subjects enrolled across the treatment arms....We therefore plan to halt further development of luvadaxistat at this time and instead will focus our efforts and resources on the advancement into Phase 3 clinical development of NBI-1117568 for schizophrenia and NBI-1065845 for major depressive disorder."

New P3 trial • P2 data • Major Depressive Disorder • Schizophrenia

Nxera Pharma to Receive US$35 Million from Neurocrine Biosciences upon Positive Phase 2 Data for Partnered Schizophrenia Candidate NBI-1117568 (GlobeNewswire) - "Nxera Pharma...announces that it will receive a US$35 million payment from Neurocrine Biosciences (‘Neurocrine’), triggered by the successful completion of the Phase 2 trial with NBI-1117568 (NBI-‘568) in adults with schizophrenia, as announced on 28 August 2024. Receipt of the US$35 million payment will be recognized as one-time revenue in the third quarter of 2024. The NBI-’568-SCZ2028 dose-finding study met its primary endpoint for the once-daily 20 mg dose and was generally safe and well tolerated at all doses studied, supporting Neurocrine’s intentions to advance NBI-‘568 into Phase 3 clinical trials in early 2025."

Financing • New P3 trial • Trial status • Schizophrenia

Efficacy, Safety, Tolerability, and Pharmacokinetics of NBI-1117568 in Adults With Schizophrenia (clinicaltrials.gov) - P2 | N=213 | Recruiting | Sponsor: Neurocrine Biosciences | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Psychiatry • Schizophrenia

Efficacy, Safety, Tolerability, and Pharmacokinetics of NBI-1117568 in Adults With Schizophrenia (clinicaltrials.gov) - P2 | N=213 | Not yet recruiting | Sponsor: Neurocrine Biosciences

New P2 trial • CNS Disorders • Psychiatry • Schizophrenia

Neurocrine Biosciences and Sosei Heptares Announce Collaboration to Develop Novel Muscarinic Receptor Agonists for Schizophrenia and Other Neuropsychiatric Disorders (PRNewswire) - "Neurocrine Biosciences, Inc....and Sosei Group Corporation ('Sosei Heptares'; TSE: 4565) announce the signing of a strategic collaboration and licensing agreement to develop novel muscarinic receptor agonists, which Neurocrine Biosciences intends to study in the treatment for schizophrenia, dementia and other neuropsychiatric disorders. Under the terms of the agreement, Neurocrine Biosciences gains development and commercialization rights to a broad portfolio of novel clinical and preclinical subtype-selective muscarinic M4, M1 and dual M1/M4 receptor agonists discovered by Sosei Heptares in development for the treatment of major neurological disorders. The most advanced program, HTL-0016878, is a selective M4 agonist. Neurocrine Biosciences plans to submit an Investigational New Drug (IND) application and initiate a placebo-controlled Phase 2 study with HTL-0016878 as a potential treatment for schizophrenia in 2022."

IND • Licensing / partnership • New P2 trial • Alzheimer's Disease • CNS Disorders • Schizophrenia

Comparison of Blood Levels of HTL0016878 From an Oral Capsule and an Oral Solution (clinicaltrials.gov) - P1; N=15; Completed; Sponsor: Heptares Therapeutics Limited; Recruiting ➔ Completed

Clinical • Trial completion

Sosei Heptares Operational Highlights and Consolidated Results for the Second Quarter and First Half 2021 (PRNewswire) - "Worldwide rights to out-licensed muscarinic agonist programs regained from AbbVie/Allergan – independent review of programs has completed, with increased investment allocated to advance the HTL'878 selective muscarinic M4 receptor agonist through clinical studies and build value ahead of future partnering....Negotiations for collaborations on this and other muscarinic programs are now in progress."

Licensing / partnership • Alzheimer's Disease • CNS Disorders • Schizophrenia