In preclinical studies, ponatinib demonstrated efficacy and oral dosing flexibility in animal models of chronic myeloid leukemia (CML), including forms of CML caused by clinically relevant variants of the target protein, BCR-ABL. Significantly, ponatinib potently inhibited a specific mutant, T315I, which is resistant to all currently available drugs. Additional preclinical studies demonstrated that ponatinib also inhibits FLT3, a target associated with acute myeloid leukemia (AML).
Preclinical studies also demonstrated that ponatinib potently inhibited additional targets that control the process of angiogenesis, or blood vessel growth, including the receptors for vascular endothelial growth factors (VEGFRs), fibroblast growth factors (FGFRs), and angiopoietin (Tie2). Inhibiting angiogenesis is a clinically validated approach to treating multiple solid tumors.
Additional preclinical studies indicate that ponatinib should be well tolerated at anticipated therapeutic dose levels in cancer patients. We believe the results of our preclinical testing support the broad potential of ponatinib in patients with leukemias as well as solid tumors.