Cogent Biosciences Presents New Preclinical Data Demonstrating Bezuclastinib as a Differentiated KIT Inhibitor with Minimal Brain Penetration
"Today Cogent presented new preclinical data that reinforces bezuclastinib's selectivity for targeting KIT mutations while demonstrating minimal brain penetration," said
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
The presentation is available on the
Forward Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding: discussion of the company's business and operations; clinical development plans and timelines including for its lead program, bezuclastinib; the expectation to initiate two additional clinical trials with bezuclastinib before the end of 2021; and the anticipated contributions of the Cogent Research Team. The use of words such as, but not limited to, "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "might," "plan," "potential," "predict," "project," "should," "target," "will," or "would" and similar words expressions are intended to identify forward-looking statements. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, our clinical results, the rate of enrollment in our clinical trials and other future conditions. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. We may not actually achieve the forecasts or milestones disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Such forward-looking statements are subject to a number of material risks and uncertainties including but not limited to those set forth under the caption "Risk Factors" in Cogents' most recent Annual Report on Form 10-K filed with the
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