OXi4503 is a dual-mechanism investigational drug that is being developed for the treatment of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). OXi4503 has a unique dual mechanism of action that disrupts the shape of tumor bone marrow endothelial cells (BMECs) through reversible binding to tubulin at the colchicine binding site, downregulating intercellular adhesion molecules. This causes alterations to the endothelial cell shape, releasing quiescent adherent tumor cells from BMECs and activating the cell cycle, making the tumor cells vulnerable to chemotherapy. OXi4503 also directly kills tumor cells via myeloperoxidase activation of a orthoquinone cytotoxic mediator. In preclinical studies, OXi4503 demonstrated potent activity in mice that were carriers of the high-risk subtype FLT3 of human AML. These data have been published in the journal Blood.
OXi4503 was studied in an investigator-sponsored Phase 1 study for the treatment of patients with AML or MDS. The open-label, dose-escalating study was sponsored in part by The Leukemia & Lymphoma Society’s Therapy Acceleration Program, and was conducted by researchers at the University of Florida. The study evaluated the safety profile, maximum tolerated dose (MTD), and biologic activity of OXi4503 in patients with relapsed or refractory AML or MDS. Adverse events attributable to OXi4503 infusion included hypertension, bone pain, fever, anemia, thrombocytopenia, and coagulopathies. Clinical data from this Phase 1 study were presented in December 2013 at the 55th American Society of Hematology Annual Meeting and Exposition in New Orleans, Louisiana.
In 2015, Mateon initiated a Phase 1b/2 clinical study, OX1222, with OXi4503 in combination with cytarabine for the treatment of relapsed/refractory AML or MDS. For more information, please go to clinicaltrials.gov.