OXi4503 (combretastatin A1 di-phosphate / CA1P) is a unique and highly potent dual-mechanism vascular disrupting agent (VDA). Like its structural analog, fosbretabulin (combretastatin A4 phosphate; ZYBRESTAT) OXi4503 is a vascular disrupting agent which blocks and destroys tumor vasculature causing tumor cell death and necrosis.

In contrast to fosbretabulin, OXi4503 also possess direct cytoxic activity. Preclinical data demonstrates that OXi4503 is metabolized by oxidative enzymes (e.g., tyrosinases and peroxidases) that are present in elevated levels in various solid and liquid tumors and tumor infiltrates. This metabolism results in the creation of reactive oxygen species (ROS) and an orthoquinone metabolite which covalently binds to proteins and nucleic acids (DNA), which exert direct cytotoxic effects on tumor cells.

Preclinical studies also demonstrate that OXi4503 has (i) single-agent activity in a range of xenograft tumor models; and (ii) synergistic or additive effects when incorporated in various combination regimens with chemotherapy, molecularly-targeted therapies (including anti-angiogenesic drugs), and radiation therapy. Treatment with OXi4503 has resulted in long-lasting eradication of detectable tumor in animal models of breast cancer, colorectal cancer and leukemia.

OXi4503 monotherapy is currently being evaluated in patients with advanced solid tumors in a Phase I dose-escalation study.