Business
Cogent Biosciences Presents New Preclinical Data Demonstrating Bezuclastinib as a Differentiated KIT Inhibitor with Minimal Brain Penetration
Currently enrolling APEX, a Phase 2 clinical study of bezuclastinib (CGT9486) for patients with Advanced Systemic Mastocytosis (AdvSM) On track to initiate
About this update from Cogent Biosciences, Inc.
[{"type":"text","content":"Currently enrolling APEX, a Phase 2 clinical study of bezuclastinib (CGT9486) for patients with Advanced Systemic Mastocytosis (AdvSM)\n On track to initiate clinical trials of bezuclastinib for patients with Non-Advanced Systemic Mastocytosis (NonAdvSM) and Gastrointestinal Stromal Tumors (GIST) in 2021\n\n\nCAMBRIDGE, Mass. and BOULDER, Colo., Oct. 7, 2021 /PRNewswire/ -- Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, today announced preclinical data providing further evidence of bezuclastinib as a differentiated, potent, and selective KIT inhibitor. The data were presented in a virtual poster at the 2021 AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics.\n\n \n \n \n \n \n \n\n \n\"Today Cogent presented new preclinical data that reinforces bezuclastinib's selectivity for targeting KIT mutations while demonstrating minimal brain penetration,\" said Andrew Robbins, President and CEO of Cogent Biosciences. \"We are excited with bezuclastinib's differentiated profile among KIT inhibitors and continue to work quickly to have three clinical trials for AdvSM, NonAdvSM and GIST patients open for enrollment in 2021.\"\nPreclinical studies evaluated the selectivity of bezuclastinib, and other KIT mutant inhibitors, against closely related kinases including PDGFRα, PDGFRβ, and CSF1R. Inhibition of these kinases has been linked to off-target toxicities such as edema and pleural effusions. Comparative screening was performed against a broad spectrum of 71 ion channels, transporters, enzymes, and cell based models, confirming prior evidence that bezuclastinib is a potent and unique inhibitor of KIT A-loop mutations (exon 17/18). In head-to-head studies comparing KIT mutant inhibitors, bezuclastinib demonstrated no activity against closely related kinases, in contrast to other KIT mutant inhibitors with demonstrated potency against PDGFRα and PDGFRβ. \nIn a nonclinical safety pharmacology study in rodents, bezuclastinib and another KIT A-loop mutant inhibitor were evaluated at doses which closely correlate with clinical exposures previously shown in clinical studies of GIST patients. After three days, bezuclastinib demonstrated minimal brain penetration with a low brain to plasma ratio. These data are sup...