In addition to discovering antibodies targeting the HGF/c-Met and ERBB3 pathways, AVEO has utilized our Human Response Platform™ to identify a number of other targets – including the Notch and FGF receptors – that appear to be potent drivers of tumor growth. AVEO has further evaluated the involvement of these targets in the development of human cancers using available human cancer databases. Targets with the ability to drive tumor growth in our tumor models and with frequent genetic alterations in human cancers were selected as targets for AVEO’s next generation of antibody drug discovery programs.
Fibroblast growth factors, or FGFs, and their receptors, FGFR1-4, represent a signaling network that plays an important role in the regulation of cell growth, survival, differentiation and angiogenesis. Work through our Human Response Platform identified FGF ligands and receptors as powerful drivers of tumor growth in a variety of tumor models and implicated the activation of the pathway in tumor development. The goal of our drug discovery efforts has been to identify specific FGFR2 and FGFR3 inhibitory antibodies that prevent activation of these receptors.
Genetic screens conducted using our Human Response Platform have demonstrated that activation of the Notch signaling pathway is a potent driver of tumor growth and confirmed its important role in tumorigenesis. The Notch receptors are a family of four receptors on the surface of cells, Notch1-4, whose activity has been shown to play important roles in normal stem cell function and in multiple aspects of tumor biology. AVEO has generated functional, specific inhibitory antibodies against both the Notch1 and Notch3 receptors, and our preclinical studies have demonstrated proof of concept with our lead Notch1 antibody candidate.