"We are excited to present these preclinical data as well as the preliminary clinical data from the ongoing AML trial with OXi4503, and look forward to further investigating the dual mechanism of activity of this novel vascular disrupting agent," said Christopher Cogle, MD, of the University of Florida and lead investigator of the clinical study. "AML is a highly lethal cancer, and there is an urgent need for therapeutic approaches based on new mechanisms of action that can be used as monotherapy or that can potentially be combined with current treatment regimens. These OXi4503 studies may demonstrate that targeting both the leukemic cells and the endothelium is a promising and safe way to treat AML in resistant populations."
"OXi4503 continues to be a valuable asset in our company's product portfolio of vascular disrupting agents. We are collaborating with Dr. Cogle and his team at the University of Florida to further explore its fundamental mechanism of activity and therapeutic potential in AML and MDS," said Jai Balkissoon, MD, FACS, and OXiGENE's Vice President of Clinical Development.
OXi4503 (combretastatin A1 diphosphate / CA1P) is a dual-mechanism vascular disrupting agent (VDA) that is being developed in clinical trials for the treatment of leukemias. Like its structural analog, ZYBRESTAT (fosbretabulin / CA4P), OXi4503 has been observed to block and destroy tumor vasculature, resulting in extensive tumor cell death and necrosis. In addition, preclinical data indicate that OXi4503 is metabolized by oxidative enzymes (e.g., tyrosinase and peroxidases), which are elevated in many solid tumors and tumor white blood cell infiltrates, to an orthoquinone chemical species that has direct cytotoxic effects on tumor cells. Preclinical studies have shown that OXi4503 has (i) single-agent activity against a range of xenograft tumor models; and (ii) synergistic or additive effects when incorporated in various combination regimens with chemotherapy, molecularly-targeted therapies (including tumor-angiogenesis inhibitors), and radiation therapy. OXi4503 has been evaluated as a monotherapy in a Phase 1 dose-escalation trial in patients with advanced solid tumors and in patients with cancers involving the liver.