Ficlatuzumab (formerly known as AV-299) is a potent hepatocyte growth factor (HGF) inhibitory antibody that binds to the HGF ligand with high affinity and specificity to inhibit HGF/c-Met biological activities.

AVEO and Biodesix, Inc. have a worldwide agreement to develop and commercialize ficlatuzumab, with VeriStrat®, a serum protein test that is commercially available to help physicians guide treatment decisions for patients with advanced non-small cell lung cancer (NSCLC). Under the terms of the agreement, AVEO and Biodesix are conducting a proof-of-concept study of ficlatuzumab in combination with erlotinib in advanced NSCLC patients selected using BDX001, a serum protein test similar to the VeriStrat test.

An exploratory analysis from AVEO’s Phase 2 study in first-line NSCLC suggested that VeriStrat was prognostic for outcome in the epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor (TKI)-treated patients and predicted differential treatment benefit for the combination of ficlatuzumab plus TKI over TKI alone. The predictive effect was observed in both progression-free survival and overall survival endpoints

About the HGF/c-Met Pathway

HGF is the sole ligand that binds to and activates a receptor called c-Met. Activation of the HGF/c-Met pathway is believed to be important in normal processes in embryonic development and wound healing, but its dysregulation is believed to play a role in cancer development, metastasis and drug resistance. HGF/c-Met has also been shown to be one of the most potent drivers of tumor growth in AVEO’s Human Response Platform™.

HGF/c-Met over-expression is observed in many solid tumors including breast, colorectal, gastric, head and neck, lung and prostate, as well as hematologic malignancies. Additionally, c-Met and EGFR are frequently co-amplified and co-expressed in a variety of tumor types; HGF/c-Met pathway upregulation can render resistance to EGFR-targeted therapies, and vice-versa.

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