According to the company, AP24534 demonstrated potent inhibition of selected kinase targets that control tumor growth and angiogenesis, notably all four receptors for fibroblast growth factors (FGFRs). The product candidate also inhibits the receptors for vascular endothelial growth factors (VEGFR), and angiopoietin (Tie-2) and, to a lesser degree, platelet-derived growth factor (PDGFR).
Activity against all four receptor families is a distinguishing feature of AP24534 that was not seen with the other multi-targeted kinase inhibitors tested, the company said. In vivo mechanistic studies also demonstrated the potent, anti-tumor activity of the product candidate in mouse models of colon cancer and melanoma.
According to the company, data from the in vivo studies show a number of key characteristics of AP24534 activity in solid tumors: potent inhibition of new blood vessel formation in angiogenesis assays; statistically significant inhibition of tumor growth with daily oral doses as low as 5mg/kg and nearly complete inhibition of growth observed at higher doses. An intermittent, twice weekly dosing schedule was also efficacious.
Ariad now plans to advance the clinical development of AP24534 in patients with solid tumors and expects to initiate Phase II clinical trials based on its assessment of the clinical data from the ongoing Phase I study of AP24534 in patients with hematological malignancies, as well as these reported preclinical data.
Timothy Clackson, senior vice president and chief scientific officer of Ariad, said: “These data demonstrate for the first time the preclinical activity of AP24534 against a variety of tumor growth and angiogenesis targets. The data highlight the potential for AP24534 to treat solid tumors based on its unique profile.
“Our dose-escalating Phase I clinical trial of AP24534, also an inhibitor of Bcr-Abl and Flt3, is progressing in patients with hematological malignancies, and we look forward to advancing AP24534 into clinical development for selected solid tumors as well.”