Sanofi-aventis and Ascenta Therapeutics, a US Biopharmaceutical company in Malvern, Pennsylvania, announced the signature of an exclusive global collaboration and licensing agreement on a number of compounds that could restore tumour cell apoptosis. These compounds inhibit the p53-HDM2 (Human Double Minute 2) protein-protein interaction, leading potentially to reactivation of p53 tumour suppressor functions and therefore enhancing current cancer treatments.
Under this agreement, sanofi-aventis will receive an exclusive worldwide license to develop, manufacture and commercialize all compounds issued from this programme. Two compounds, MI-773 and MI-519-64, are currently expected to enter preclinical development in 2010.
Ascenta has in-licensed those compounds from the University of Michigan. Both sanofi-aventis and Ascenta will provide funding for the ongoing research of p53-HDM2 inhibitors at the University of Michigan and Ascenta may participate in ongoing research activities and potential future clinical development.
"This new partnership continues to illustrate sanofi-aventis' commitment to develop innovative targeted therapies in Oncology," declared Debasish Roychowdhury, senior vice president, global oncology, sanofi-aventis. "The inhibition of protein-protein interaction is always a challenge in discovery, and the finding of potent and selective compounds could offer an attractive new therapeutic approach for cancer patients. This approach is perfectly in line with the company's strategy to find new drugs focused on patient specific needs".
Under the terms of the agreement, Ascenta will receive an upfront payment, as well as development, regulatory and commercial milestone payments. All such payments could reach a total of US$ 398 million. In addition, Ascenta is eligible to receive tiered royalties on worldwide product sale.
The p53 tumour suppressor protein is a major mediator of growth arrest and apoptosis in response to a broad array of cellular damage. It has been called the "guardian of the genome" through its role in controlling the cell cycle and monitoring the integrity of the genome. HDM2 protein is the principal cellular antagonist of p53. HDM2 binding to p53 leads to p53 degradation. Loss of p53 functions occurs in 50 per cent of all cancers through mutation of p53 gene and also through over-expression of HDM2 protein, due to transcriptional regulation of the HDM2 gene amplification. Therefore, blocking the interaction between p53 and HDM2 in cancer cells should reactivate p53 tumour suppressor functions and enhance current cancer treatments.