Crolibulin™ is a novel small molecule vascular disruption agent and apoptosis inducer for the treatment of patients with advanced solid tumors. Crolibulin™ has shown promising vascular targeting activity with potent anti-tumor activity in pre-clinical in vitro and in vivo studies. The molecule has been shown to induce tumor cell apoptosis and selectively inhibit growth of proliferating cell lines, including multi-drug resistant cell lines. Murine models of human tumor xenografts demonstrated Crolibulin™ inhibits growth of established tumors of a number of different cancer types. Two manuscripts on this compound were published in the November 2004 issue of Molecular Cancer Therapeutics.

Pre-clinical studies suggest that the anti-tumor effects of Crolibulin™ may be the result of a dual mechanism, a direct effect on disruption of tumor vascular endothelial cells leading to hypoxia and central tumor necrosis, as observed with vascular disruption agents, and a second effect on tumor apoptosis.

Stage of Development

In 2009, EpiCept announced that it had completed the first study in man for Crolibulin™. EpiCept identified the maximum tolerated dose of Crolibulin™ in the Phase I study after 1 hour and 4 hour infusion. Crolibulin™ was administered as a single agent in increasing doses to small cohorts of patients with advanced solid tumors. A total of 33 patients were enrolled in the study. The study provided evidence of clinical symptomatic activity and radiographic evidence of efficacy in end-stage cancer patients. EpiCept intends to initiate a Phase 1B combination trial for the compound with other chemotherapeutic agents in 2010.