The Astellas subsidiary OSI Pharmaceuticals will pay Aveo Pharmaceuticals $25 million to exercise its option to take on specific elements of the latter’s Human Response platform™ (HRP) technology in support of its own clinical development programs. The transferred technology will include components of the HRP platform for identifying and characterizing novel epithelial-mesenchymal transition (EMT) agents and patient-selection biomarkers.
OSI inked its option to Aveo’s HRP technology in 2009. The two firms had originally teamed up on a drug discovery and translational research collaboration in 2007. This has been focused on the development of therapeutics that target the underlying mechanisms of EMT in cancer and the development of patient-selection biomarkers to support OSI’s pipeline. In 2009 the firms’ collaboration was expanded to validate cancer targets and use key elements of the HRP translational research platform in support of OSI’s ongoing clinical development programs.
“OSI’s collaboration with Aveo has demonstrated the significant value the company’s HRP and related insights provide to us for exploiting the biology of EMT,” remarks Naoki Okamura, OSI’s CEO. “Incorporating certain elements of the Aveo platform and bioinformatics capabilities in house will enable us to further differentiate our approach to the discovery, development, and commercialization of novel new medicines for the treatment of cancer.”
Aveo’s Human Response Platform is based on the company’s genetically defined mouse models of human cancer, in which each model is engineered to contain signature genetic mutations that are present in human disease. The firm claims the platform can be used to help address three key issues in cancer drug discovery and clinical development. In cancer target identification and validation, the HRP platform can reportedly facilitate the identification of cancer-causing gene candidates that are most important to tumor growth. In drug discovery the technology enables the development of tumor models that are driven by the gene of interest, for use in the evaluation and selection of gene targeting drug candidates. The platform can in addition be exploited to help identify biomarkers of drug response and resistance.
Aveo is also exploiting its technologies to develop an in-house pipeline of oncology therapeutics. The company's lead product candidate tivozanib, however, was licensed in from Kyowa-Kirin licensed in 2007, for development in all territories outside Asia. Tivozanib is a small molecule oral inhibitor of vascular endothelial growth factor (VEGF) receptors 1, 2, and 3. The drug is currently in Phase III development against advanced renal cell carcinoma, in Phase I trials as monotherapy against lung cancer, and as combination therapy against colorectal and breast cancers.
Aveo has separately utilized the HRP platform to identify two monoclonal antibody candidates. AV-299 binds to hepatocyte growth factor and is undergoing Phase II evaluation in patients with non-small-cell lung cancer. AV-203 is a preclinical-stage antibody candidate that targets the ErbB3 receptor, and is being developed in partnership with Biogen Idec.
In addition, Aveo has used the HRP technology to identify targets that appear to drive tumor growth. The RON receptor, Notch receptors, and FGF receptors have been selected as targets for the development of antibody drug candidates.
OSI, meanwhile, is focusing its cancer research on the process of EMT, which is believed to represent a marker of tumor progression such that tumors expressing mesenchymal markers having a greater tendency to be invasive and metastasize than tumors that only express epithelial markers. Tumors expressing mesenchymal markers are also thought to have a worse prognosis than tumors expressing epithelial markers, OSI points out. EMT is a transcriptional reprogramming process whereby epithelial cells change by expressing proteins and morphological features that are normally associated with mesenchymal, fibroblastic cells. Moreover, the firm claims, because mesenchymal tumor cells co-opt different sets of oncogenic signaling pathways, EMT targets represent a novel therapeutic opportunity.
OSI’s interest in EMT originated through translational research efforts focused on understanding the mechanisms that allow some patients to benefit from its anticancer drug Tarceva® (erlotinib) more than others. The firm’s EMT research aims to generate a deeper insight into the processes of EMT in solid tumors, in order to direct the development of more effective and safer mechanism-based anticancer drugs