Horizon Discovery, a provider of research tools to support translational genomics research and the development of personalized medicines, and AstraZeneca have entered into a research, collaboration and license agreement to explore oncology-relevant genotypes with the aim of identifying and validating a number of novel drug targets.
The deal is the second collaboration between AstraZeneca and Horizon, and follows the announcement in April 2013 of an oncology discovery program to explore Horizon's first-in-class kinase target program, HD-001. The HD-001 program recently won the SCRIP Award for Licensing Deal of the Year for 2013.
A defined set of genotypes will be queried by Horizon for synthetic lethality. Horizon will carry out in vitro screening activities using its proprietary siRNA Platform. RNAi hits resulting from this first stage will then be validated by Horizon, through techniques including pathway analysis, confirmation of activity in endogenously mutant versus wild type cell lines (X-MAN TM), functional assays or gene knock-in/knockout assays. AstraZeneca may exercise exclusivity over any validated targets.
Synthetic lethality occurs where the combination of mutations in two or more genes leads to cell death, but a mutation in just one of those genes does not. Synthetic lethal screens have demonstrated great potential in oncology, as these pairs of mutations could be used to selectively kill cancer cells, but leave normal cells relatively unharmed.
Horizon will receive an undisclosed upfront payment, and is eligible for subsequent payments of up to $88 million in milestones if compounds are developed by AstraZeneca against an undisclosed number of targets identified through the research collaboration.
Horizon's X-MAN isogenic cell lines accurately model the disease-causing mutations found in patients with cancer, and increasingly other diseases. Horizon creates the isogenic cell lines using its precision genome-editing GENESIS TM platform, comprising rAAV, ZFN and CRISPR technologies, to engineer specific disease-related mutations into model cell lines. These models help researchers understand how complex genetic diseases manifest themselves in patients, and can reduce the cost of bringing to market new personalized therapies by streamlining many aspects of drug development including target identification, target validation, assay development, drug screening, lead optimization and biomarker-driven clinical trial design.