Cancer cells

UK-based Horizon Discovery and British-Swedish drug manufacturer AstraZeneca have entered into a research, collaboration and licensing agreement to explore a range of oncology-relevant genotypes in order to identify and validate several new cancer drugs.

The deal marks the second collaboration between the two companies and follows the announcement in April 2013 of an oncology discovery programme to explore Horizon’s kinase target programme, HD-001.

Horizon Discovery CEO Darrin Disley said: "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.

As part of the deal, a defined set of genotypes will be analysed by Horizon for synthetic lethality and the company will also conduct in vitro screening activities using its proprietary siRNA Platform.

Horizon will use techniques such as pathway analysis, confirmation of activity in endogenously mutant versus wild type cell lines (X-MAN), functional assays, or gene knock-in/knockout assays for validating the RNAi hits resulting from this first stage.

Synthetic lethality occurs when the combination of mutations in two or more genes leads to cell death, but a mutation in just one of those genes does not.

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"Our X-MAN isogenic disease models incorporate patient-relevant genetic context, and allow large-scale, timely and systematic screens for the first time."

The companies said that synthetic lethal screens have shown potential in oncology, as these pairs of mutations could be used to selectively kill cancer cells, but leave normal cells relatively unharmed.

AstraZeneca head of the Oncology Innovative Medicines Unit Susan Galbraith said: "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 also eligible to receive subsequent payments of about $88m in milestones if compounds are developed by AstraZeneca as part of the research collaboration.

According to Horizon, its X-MAN isogenic cell lines accurately model the disease-causing mutations found in patients with cancer, and increasingly other diseases.

The company creates the isogenic cell lines using its precision genome-editing GENESIS platform, comprising rAAV, ZFN and CRISPR technologies, to engineer specific disease-related mutations into model cell lines.

Image: Synthetic lethal screens have demonstrated great potential in oncology. Photo: courtesy of