ARIAD Pharma (ARIA) Reports Postive Pre-Clinical Data for pan-BCR-ABL Inhibitor Ponatinib
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ARIAD Pharmaceuticals, Inc. (Nasdaq: ARIA) reports pre-clinical results of pan-BCR-ABL inhibitor, ponatinib, shows potent inhibition of all four members of the fibroblast growth factor receptor (FGFR) family of tyrosine kinases that are abnormally expressed in multiple cancers.
From the release: "cent research has established that FGF receptors 1 to 4 are activated through multiple mechanisms in certain solid tumors and represent promising targets for antitumor therapy. The new data on ponatinib demonstrate potent activity against a broad range of tumor cells activated by all four FGFRs, in vitro and in vivo. In a panel of 14 cell lines representing multiple different tumor types including endometrial, bladder, gastric, breast, lung and colon cancer, ponatinib potently and selectively inhibited FGFR-mediated signaling and cell growth. Four other tyrosine kinase inhibitors with FGFR inhibitory activity that are in clinical development were substantially less active, and none potently blocked all four FGF receptors.
In mouse models of FGFR-driven tumors, daily oral dosing of ponatinib reduced tumor growth and inhibited signaling in all 3 FGFR-driven models examined. Ponatinib reduced tumor growth by 80 percent in mouse models of bladder and endometrial cancers and induced tumor regression in a model of gastric cancer. Potency was similar to that previously observed in BCR-ABL-driven models of chronic myeloid leukemia (CML). Importantly, the Phase 1 trial of ponatinib in CML shows that plasma concentrations of ponatinib required for inhibition of all four FGFRs can be sustained at well-tolerated doses in patients."
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From the release: "cent research has established that FGF receptors 1 to 4 are activated through multiple mechanisms in certain solid tumors and represent promising targets for antitumor therapy. The new data on ponatinib demonstrate potent activity against a broad range of tumor cells activated by all four FGFRs, in vitro and in vivo. In a panel of 14 cell lines representing multiple different tumor types including endometrial, bladder, gastric, breast, lung and colon cancer, ponatinib potently and selectively inhibited FGFR-mediated signaling and cell growth. Four other tyrosine kinase inhibitors with FGFR inhibitory activity that are in clinical development were substantially less active, and none potently blocked all four FGF receptors.
In mouse models of FGFR-driven tumors, daily oral dosing of ponatinib reduced tumor growth and inhibited signaling in all 3 FGFR-driven models examined. Ponatinib reduced tumor growth by 80 percent in mouse models of bladder and endometrial cancers and induced tumor regression in a model of gastric cancer. Potency was similar to that previously observed in BCR-ABL-driven models of chronic myeloid leukemia (CML). Importantly, the Phase 1 trial of ponatinib in CML shows that plasma concentrations of ponatinib required for inhibition of all four FGFRs can be sustained at well-tolerated doses in patients."
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