Nxera Pharma's oral compound advances in neurological treatment

A groundbreaking study has been initiated to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of NBI-1117567 in healthy adult participants. NBI-1117567 is a selective agonist targeting muscarinic M1 and M4 receptors, showing potential in treating cognitive symptoms associated with various neurological and neuropsychiatric conditions.

Muscarinic receptors are critical for numerous body functions, including brain activity. They have been long considered a viable target for addressing cognitive and neuropsychological symptoms in diseases such as Schizophrenia, Alzheimer’s, and Parkinson’s. However, past efforts to develop selective agonists were often thwarted by side effects caused by activating other receptor subtypes. NBI-1117567, by focusing on M1 and M4 receptors, may circumvent these issues, presenting a new and effective treatment pathway without the adverse effects seen in earlier compounds.

The development of NBI-1117567 is supported by a collaboration and licensing agreement between Nxera Pharma and Neurocrine Biosciences, established in November 2021. This agreement grants Neurocrine the global development and commercialization rights to an array of muscarinic receptor agonists discovered by Nxera. Meanwhile, Nxera retains the rights to develop M1 agonists specifically in Japan. Under this deal, Nxera will receive substantial funding for research and development, achievement-based milestones, and royalties, contingent on meeting specific criteria.

This collaborative effort signifies a significant step forward in the pharmaceutical industry's quest to create innovative therapies targeting unmet medical needs in neurological and neuropsychiatric disorders. As the Phase 1 clinical study of NBI-1117567 progresses, stakeholders are keenly awaiting further insights into its therapeutic potential and its ability to transform treatment paradigms for cognitive symptoms in neurological conditions.

Mild cognitive impairment (MCI), while having no single cause, is often linked to early Alzheimer's disease. The outcomes of MCI vary widely; symptoms may remain stable for years, progress to Alzheimer's dementia, or, in some instances, improve over time. According to the Mayo Clinic, MCI involves brain changes similar to those seen in Alzheimer's and other forms of dementia, but to a lesser extent. These changes include beta-amyloid plaques, tau protein tangles, and Lewy bodies, which are also associated with Parkinson's disease and some Alzheimer's cases. Other changes could involve small strokes or reduced blood flow within the brain.

Brain imaging studies indicate that MCI may involve a decreased hippocampus size, enlarged brain ventricles, and reduced glucose utilization in key brain regions. The most significant risk factors for MCI include advancing age and carrying the APOE e4 gene, which is also linked to Alzheimer's disease. However, possessing this gene does not guarantee cognitive decline. Other risk factors include diabetes, smoking, high blood pressure and cholesterol, obesity, depression, and obstructive sleep apnea.

Nxera Pharma, formerly Sosei Heptares, is a technology-driven biopharmaceutical company focused on developing new specialty medicines to meet unmet medical needs both in Japan and globally. Neurocrine Biosciences is dedicated to providing breakthrough treatments for rare and under-addressed diseases. Together, they are advancing an extensive pipeline of over 30 active programs, ranging from discovery to late-stage clinical development, through internal efforts and partnerships with leading pharmaceutical and biotech companies.