Highly selective Orexin 1 antagonist may have treatment potential in multiple therapeutic conditions
Boston, MA – February 15, 2024 – Cerevance, a company focused on developing precision novel therapeutics for central nervous system (CNS) diseases, today announced a publication describing the discovery and initial development of CVN766 in the peer-reviewed journal, Bioorganic & Medicinal Chemistry Letters. In the publication titled, “Discovery and first-time disclosure of CVN766, an exquisitely selective orexin 1 receptor antagonist,” the authors describe the development of CVN766 to be over 1,000-fold more selective for the orexin 1 receptor (Ox1R) than the orexin 2 receptor (Ox2R). This selectivity avoids causing somnolence and sleep that is regulated by Ox2R.
Ox1R is highly expressed in critical brain structures involved in regulating mood, motivation, and behavior, such as the locus coeruleus and raphe nucleus controlling noradrenergic and serotonergic neurotransmission, respectively, and the reward pathways of the ventral tegmental area/nucleus accumbens. Dysfunction of this target, Ox1R, is implicated in psychiatric disorders, such as schizophrenia, addictions (including food), and anxieties.
“CVN766 has demonstrated high brain permeability, prolonged receptor occupancy, and a pharmacokinetic and safety profile suitable for clinical evaluation across various psychiatric indications,” said Mark Carlton, Ph.D., chief scientific officer for Cerevance. “We believe CVN766’s selectivity for solely Ox1R versus Ox2R is several magnitudes greater than compounds previously developed by others that have not achieved clinical success.”
The publication can be found at the following link: https://www.sciencedirect.com/science/article/pii/S0960894X24000313?ref=pdf_download&fr=RR-2&rr=8546332ee95b2f69 and on the Cerevance website on the Publications page.
About CVN424
CVN424 is a first-in-class non-dopamine therapy that selectively modulates GPR6, an orphan G-protein coupled receptor. Expression of GPR6 is largely confined to the subset of striatal projection neurons that give rise to the indirect (striatopallidal) pathway, important in the control of movement. CVN424 shows promise in improving both the motor (significant reduction of 1.5 hours in OFF time versus placebo) and non-motor symptoms of Parkinson's disease. Further, CVN424 has shown to be safe and well tolerated without dopaminergic side effects and may also have disease-delaying effects.
About Cerevance
Cerevance is focused on the development of precision treatments for central nervous system (CNS) disorders, prioritizing chronic neurodegenerative conditions such as Alzheimer's disease, Parkinson's disease, and Amyotrophic Lateral Sclerosis (ALS). Utilizing a large and growing collection of over 14,000 human brain tissue samples, Cerevance is generating an unprecedented level of expression and epigenetic data thereby enabling the company to identify the most promising targets for the next generation of treatments for CNS disorders.
The company utilizes its proprietary Nuclear Enriched Transcript Sort sequencing (NETSseq) platform and advanced machine learning techniques to uncover the gene expression profiles of select cell types to identify novel targets that are uniquely expressed in relevant circuits affected by diseases or are altered in disease states. With the information obtained from its research, combined with the expertise of its team of scientists and drug developers, Cerevance is advancing multiple therapeutics that selectively modulate the discovered targets. These treatments are progressing through clinical development, with CVN424, CVN766, and CVN293 being the furthest along in the pipeline. CVN424 is a first-in-class non-dopamine therapy that shows promise in improving both motor and non-motor symptoms of Parkinson's disease and may also have disease-delaying effects. CVN766 is a potent antagonist of the orexin 1 receptor with high selectivity over the orexin 2 receptor which may benefit a variety of psychiatric conditions including schizophrenia, anxiety/panic, binge eating/obesity, substance use disorder, and Prader-Willi Syndrome. CVN293 is a novel blocker of potassium efflux in glia, regulating the inflammasome in individuals living with ALS and Alzheimer's disease.
By leveraging its extensive collection of brain tissue samples, employing advanced technologies, and generating actionable data, Cerevance aims to transform the lives of patients affected by CNS diseases.
Contacts
Cerevance:
Johnna Simoes, ir@cerevance.com
Media
Andrew Mielach, amielach@lifescicomms.com, +1-646-876-5868
