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™),
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
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
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™ 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™ 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™
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
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