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Ariad Pharmaceuticals Inc Presents New Preclinical Data Showing Ponatinib Is Potent Inhibitor Of RET And FGFR, Two Oncogenic Drivers Of Non-Small Cell Lung Cancer


Monday, 8 Apr 2013 07:35am EDT 

Ariad Pharmaceuticals Inc announced presentation of preclinical data on ponatinib. The first preclinical study, Ponatinib is a potent inhibitor of activated variants of RET found in MTC and NSCLC, shows that ponatinib inhibits naturally occurring activating mutants of RET found in MTC and NSCLC at clinically achievable plasma concentrations. The potency of ponatinib was found to substantially exceed that of other approved tyrosine kinase inhibitors with RET activity. These results provide support for the clinical evaluation of ponatinib in patients with RET-driven cancers. In the second preclinical study, Ponatinib potently inhibits the activity of mutant variants of FGFR commonly found in endometrial, lung and other cancers, the ability of ponatinib to inhibit a broad panel of naturally occurring mutant variants of FGFR1, 2, 3, and 4 was evaluated. Ponatinib potently blocked a variety of mutant variants of FGFR, with particularly promising activity against mutant variants of FGFR2 that have been observed in endometrial and squamous cell carcinomas (SCCs) of the lung. Specifically, ponatinib inhibits the eight mutants that make up more than 90% of the mutations observed in endometrial cancer patients, and six mutants observed in SCC at clinically achievable plasma concentrations. Ponatinib also shows encouraging activity against FGFR1/3 fusion proteins found in glioblastoma multiforme. 

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