AVEO Pharmaceuticals, Inc. presented a novel human hepatocyte growth factor (HGF) knock-in model and announced data demonstrating strong preclinical activity of SCH 900105 (AV-299), a highly potent antagonist of hepatocyte growth factor/scatter factor (HGF/SF), at the American Association for Cancer Research (AACR) 100th Annual Meeting in Denver, Colorado. Additionally, data assessing Fibroblast Growth Factor Receptor-2 (FGFR-2) response to an FGFR antagonist in a novel FGFR-2 driven model were also highlighted.
“Preclinical data presented at AACR underscore the unique capability of our proprietary Human Response Platform to guide drug development strategies for our lead antibody candidate SCH 900105 (AV-299), currently in Phase 1 clinical development, and reinforce the broad potential of our rapidly maturing proprietary antibody pipeline,” stated Tuan Ha-Ngoc, president and chief executive officer of AVEO Pharmaceuticals. “Through internal antibody discovery efforts and selective in-licensing of targeted small molecule therapeutics, AVEO is building a diversified product pipeline and rapidly advancing toward its vision of becoming a fully integrated oncology company.”
The HGF/c-Met pathway in human cancer is frequently activated by stromal derived HGF. In order to recreate the tumor-stromal-endothelial interactions of HGF/c-Met axis in preclinical efficacy models, AVEO created a human HGF “knock-in” host strain, replacing the murine HGF gene with human HGF gene. Multiple paracrine models were established in this host strain, allowing the testing of SCH 900105 (AV-299) in a setting more relevant to human disease.
Preclinical data presented at AACR demonstrated that SCH 900105 (AV-299) is efficacious in glioblastoma multiforme, non-small cell lung cancer (NSCLC), and pancreatic cancer models. In the U87 GBM model, SCH 900105 (AV-299) administration resulted in complete regressions even after withdrawal of treatment. In addition, several combination studies performed with SCH 900105 (AV-299) and other targeted therapeutics, chemotherapies and anti-angiogenic agents demonstrated additive efficacy in vivo.
AVEO identified FGFR-2 as an important tumor maintenance gene utilizing its proprietary in vivo genetic screen technology. To further validate the target, and to create a FGFR-2 driven tumor model, AVEO applied its directed complementation technology to develop a novel FGFR-2 driven breast tumor model. Drug efficacy studies using a non-selective FGFR inhibitor resulted in pharmacodynamic inhibition of the introduced human FGFR2 protein and led to significant tumor growth inhibition.
Recent data from human correlative and mutational studies has implicated FGFR2 as a potentially important target in human breast cancer.
Release date: April 19, 2009
Source: AVEO Pharmaceuticals