On October 7, 2021 Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, reported preclinical data providing further evidence of bezuclastinib as a differentiated, potent, and selective KIT inhibitor (Press release, Cogent Biosciences, OCT 7, 2021, View Source [SID1234590926]). The data were presented in a virtual poster at the 2021 AACR (Free AACR Whitepaper)-NCI-EORTC Virtual AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"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."

Preclinical 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.

In 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 supported by a separate neurobehavioral study of bezuclastinib in rodents in which no CNS-related effects were observed. The absence of brain penetration is a preferred feature for a KIT mutant inhibitor as CNS-related adverse events have been observed clinically with some commercially available mutant KIT inhibitors.

Poster Presentation Details for Bezuclastinib:
Title: Preclinical data identifies bezuclastinib as a differentiated KIT inhibitor with unique selectivity to KIT D816V and minimal evidence of brain penetration
Virtual Poster Number: P257
Date/Time: All poster presentations are made available by the conference at the opening of the meeting on October 7, 2021, at 9:00 am ET.

The presentation is available on the Cogent Biosciences website at: View Source