Cerevance Doses First Subject in Phase 1 Clinical Study of CVN293, a Selective Inhibitor of KCNK13 Designed to Selectively Modulate Neuroinflammation, for the Treatment of ALS and Alzheimer’s Disease
- Category: Small Molecules
- Published on Tuesday, 19 September 2023 16:37
- Hits: 513
BOSTON, MA, USA I September 19, 2023 I Cerevance, a private, clinical-stage drug discovery and development company focused on advancing novel, precision neuroscience therapeutics for central nervous system (CNS) diseases using the company’s proprietary Nuclear Enriched Transcript Sort sequencing (NETSseq) platform, today announced that the first subject has been dosed in the Phase 1 clinical study evaluating the safety, tolerability, and pharmacokinetics of CVN293.
“We are very pleased to advance CVN293, a selective small-molecule inhibitor of the novel target KCNK13 into Phase 1 clinical development,” shared Craig Thompson, chief executive officer of Cerevance. “KCNK13, an important modulator of neuroinflammation, was selectively identified using NETSseq and represents the power of the Cerevance platform in discovering precision neuroscience targets. This is an important milestone as we continue to translate scientific discoveries into potential therapeutic options to address neuroinflammatory conditions.”
The Phase 1 trial is a combined single ascending dose (SAD) and multiple ascending dose (MAD) study designed to investigate the safety, tolerability, and pharmacokinetics of orally administered CVN293 in healthy subjects. Single (SAD phase) or repeated doses (MAD phase) of CVN293 will be administered in a double-blind, randomized, placebo-controlled, dose-escalating design. A total of 64 healthy male and female subjects aged 18 to 55 years will be enrolled (40 subjects in the SAD study and 24 subjects in the MAD study). There will be 5 cohorts of 8 subjects in the SAD study and 3 cohorts of 8 subjects in the MAD study. In each cohort, subjects will be randomized 6:2 to receive either CVN293 or placebo, respectively.
CVN293 is an investigational, potent, and selective inhibitor of KCNK13, a novel target shown by NETSseq to be selectively expressed in brain microglia, a cell type that is central in neuroinflammation and has been implicated in many neurodegenerative diseases, including Amyotrophic Lateral Sclerosis, Alzheimer’s disease and severe age-related macular degeneration. The extremely low levels of expression of KCNK13 in peripheral macrophages, in contrast to targets being pursued by others, suggests that CVN293 may effectively address inflammation in the brain without compromising peripheral immune function, an area of particular importance in the often older and fragile immunosenescence (a decline in immune function associated with aging) patients. The potential benefits of CVN293's selective action could mean a more targeted, precision neuroscience approach to treating neuroinflammation.
Cerevance is focused on the development of 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 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.