Phase 1 Study Initiated: NBI-1140675 for Neurological and Neuropsychiatric Conditions

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Neurocrine Biosciences today announced the initiation of a phase 1 clinical study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of investigational compound NBI-1140675 in healthy adult participants. NBI-1140675 is an oral, selective second-generation small molecule inhibitor of the vesicular monoamine transporter 2 (VMAT2) in development for the potential treatment of certain neurological and neuropsychiatric conditions, such as tardive dyskinesia.

"We are focused on extending our bench of VMAT2 inhibitors in development, building on our successful discovery and development of valbenazine for the treatment of tardive dyskinesia and chorea in Huntington disease," said Eiry W. Roberts, MD, chief medical officer at Neurocrine Biosciences. "NBI-1140675 is an internally discovered, highly potent, selective VMAT2 inhibitor with the potential to provide differentiated benefit in treating certain neurological and neuropsychiatric conditions."

NBI-1140675 is 1 of 2 second-generation VMAT2 inhibitor undergoing evaluation by Neurocrine in phase 1 clinical studies, alongside NBI-1065890. According to invesitgators, VMAT2 inhibitors have been clinically validated as effective treatments for hyperkinetic movement disorders and play an important role in presynaptic dopamine storage and release.

"We're excited to bring this next-generation, internally discovered, highly potent, oral, selective VMAT2 inhibitor into the clinic with the hope of providing differentiated benefit in treating certain neurological and neuropsychiatric conditions," said Roberts.²

Valbenazine, another selective VMAT2 inhibitor, received US Food and Drug Administration (FDA) approval in 2017, making it the first drug ever developed for the treatment of tardive dyskinesia. In 2023, valbenazine also received FDA approval as a treatment for chorea associated with Huntington disease. Currently, valbenazine is in phase 3 clinical studies as an adjunctive treatment with antipsychotics for schizophrenia and as a treatment for dyskinetic cerebral palsy.

Additionally, top-line data shared in late February from the phase 4 study, KINECT-PRO, demonstrated clinically meaningful and sustained effects of valbenazine (Ingrezza) capsules on the physical, social, and emotional impacts experienced by patients living with tardive dyskinesia, regardless of severity or underlying psychiatric conditions. This is the first study to show patient-reported impact of a VMAT2 inhibitor on tardive dyskinesia using multiple clinically validated scales. Vitally, self-reported outcome measures provide a more complete perspective on a patient's experience of living with tardive dyskinesia. Results showed significant and sustained improvements from baseline on all observed patient-reported outcome measures, including patients with mild or moderate/severe TD, with improvements observed as early as 4 weeks at the lowest dose of Ingrezza. The full results of this study will be shared at upcoming conferences.³

"Tardive dyskinesia can significantly impact many aspects of patients' lives, including daily activities, work or school attendance and social interactions," said Eiry W. Roberts, MD, Chief Medical Officer, Neurocrine Biosciences. "The data from the KINECT-PRO trial, which was designed to follow typical clinical practice, show that patients and clinicians observed substantial reduction in the impact and severity of TD, as well as improvement in overall quality of life with use of Ingrezza. Importantly, patients reported significant improvements across measures regardless of their underlying psychiatric conditions or the baseline severity of their TD involuntary movement symptoms."³

References

1. Neurocrine Biosciences announces initiation of phase 1 clinical study evaluating NBI-1140675, a second-generation VMAT2 inhibitor, in healthy adults. News release. March 5, 2025. https://www.prnewswire.com/news-releases/neurocrine-biosciences-announces-initiation-of-phase-1-clinical-study-evaluating-nbi-1140675-a-second-generation-vmat2-inhibitor-in-healthy-adults-302392294.html

2. Neurocrine Biosciences announces initiation of phase 1 clinical study evaluating effects of NBI-1065890, a second-generation VMAT2 inhibitor, in healthy adults. News release. March 28, 2024. Accessed March 5, 2025. https://neurocrine.gcs-web.com/news-releases/news-release-details/neurocrine-biosciences-announces-initiation-phase-1-clinical-0

3. Kuntz L. Significant improvements in functionality and quality of life: new data on Ingrezza for tardive dyskinesia. Psychiatric Times. February 27, 2025. https://www.psychiatrictimes.com/view/significant-improvements-in-functionality-and-quality-of-life-new-data-on-ingrezza-for-tardive-dyskinesia