Abstract #1235: EPI0030, a humanized anti-VEGF rabbit monoclonal antibody, exhibits potent activity in preclinical models

Abstract

Tumor growth and development is dependent on the formation of a neovasculature. Vascular endothelial growth factor-A (VEGF-A) play a key role in the vascular development of tumors. Finding new and effective therapies targeting tumor angiogenesis represents an unmet need. Here we present the generation and characterization of a novel humanized anti-VEGF rabbit monoclonal antibody, EPI0030, which was generated using Epitomics\#8217;s robust RabMab\#8482; platform and our proprietary Mutational-Lineage-Guided (MLG)-drived humanization technology. EPI0030 selectively blocks VEGF-A binding to VEGFR2, the receptor primarily responsible for tumor angiogenesis. This antibody is characterized and compared with marketed anti-cancer agent Avastin by: i) increased affinity for VEGF-A, ii) improved blocking of VEGF binding to VEGFR and its signal transduction, and iii) significantly increase in in vivo antitumor potency. In an established preclinical NCI-H460 lung cancer model, EPI0030 reduced the growth of the tumors by 86% with a concomitant decrease in microvessel density, while Avastin only moderately inhibited the tumor growth by 37%. The anti-tumor activity of EPI0030 compared favorably to that of Avastin, supporting that selective blocking of VEGF binding to VEGFR2 by EPI0030 may ultimately offer safety or efficacy benefits over current marketed cancer drugs. Additional preclinical studies are planned to evaluate EPI0030 as a potential clinical candidate based on its anti-tumor activity.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1235.