Horizon Discovery (Horizon) and AstraZeneca have entered into a research, collaboration and license agreement to explore a range of oncology-relevant genotypes with the aim of identifying and validating a number of novel drug targets. This 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.
Under the terms of the agreement 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 vs. 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.
Dr Darrin M Disley, CEO at Horizon Discovery, said: "We are delighted to have extended our relationship with AstraZeneca's Oncology team with this latest agreement. Horizon is uniquely placed in the translational genomics field for investigation of synthetic lethality, as our X-MAN isogenic disease models incorporate patient-relevant genetic context, and allow large scale, timely and systematic screens for the first time. Combined with our high-throughput RNAi and bioinformatics technology platforms, we have a powerful offering."
Susan Galbraith, Head of the Oncology Innovative Medicines Unit at AstraZeneca, commented: "AstraZeneca's strategy of collaborating with innovative organizations like Horizon allows us to broaden our oncology research efforts and complement our own internal capabilities. Partnering Horizon's excellent capabilities in synthetic lethal screens and validation with our strong oncology discovery and development expertise offers real potential to address the need for novel cancer therapeutics, and ultimately to make a difference to patients."
Under the terms of the agreement, 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.
Notes to Editors
About Horizon Discovery www.horizondiscovery.com/
Horizon Discovery Limited (Horizon) is a leading provider of research tools to support translational genomics research and the development of personalized medicines. Using GENESISTM, Horizon is able to alter any endogenous gene sequence of a human or mammalian cell-line quickly, reliably and without introducing unwanted and confounding genotypes and/or phenotypes.
Horizon has applied GENESIS to create over 500 X-MAN TM cell lines, the world's first source of genetically-defined and patient-relevant human cell lines, accurately modeling the disease-causing mutations found in cancer patients. These 'patients-in-a-test-tube' are being used by academic and industry leaders to identify the effect of individual or compound genetic mutations on drug activity, patient responsiveness, and resistance, leading to the successful prediction of which patient sub-groups will respond to currently-available and future drug treatments. This enables the design of shorter, more focused, and less expensive clinical trials, ultimately providing the tools to identify the 'right drugs' for the 'right patients' based upon the unique genetic mutations that define their disease.
In addition to the X-MAN cell lines, Horizon provides GENESIS and X-MAN TM derived products and services, with industrial application in: bio-pharmaceutical process optimization; clinical diagnostic development; drug discovery & development; and the provision of reference standards for genomic-based clinical research platforms.
AstraZeneca is a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of cardiovascular, metabolic, respiratory, inflammation, autoimmune, oncology, infection and neuroscience diseases. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information please visit: www.astrazeneca.com
Dr. Darrin M. Disley, CEO
Email: [email protected]
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