Horizon and Domainex to collaborate on TBK1 IKKε oncology project

1. Horizon Discovery and Domainex Ltd Collaborate to Support Lead
Optimization Oncology Program
Horizon’s isogenic cell lines accurately modeling tumor mutations to be used to profile
lead compounds
Cambridge, UK, 06 August 2012: Horizon Discovery Ltd (Horizon), a leading provider of
research tools to support the development of personalized medicines, today announced it has
signed an agreement with Domainex to support Domainex’s TBK1/ IKKε oncology research and
development program, which is conducted in collaboration with The Institute of Cancer Research,
London. Under the terms of the agreement, Horizon will profile a number of lead compounds
against a panel of X-MAN™ isogenic disease model human cell lines, which accurately model the
mutations found in cancer cells.
Profiling of Domainex’s lead TBK1/IKKε dual inhibitor molecules against the X-MAN cell lines will
enable identification of the effect of individual mutations on drug activity and resistance and
prediction of which patient sub-groups will respond. This will help guide the medicinal chemistry
optimization program and will provide important patient stratification data for future partnering.
“Horizon’s oncology and genome editing expertise are a valuable complement to our in-house
biochemistry, medicinal chemistry and computer aided drug design capabilities,” commented
Eddy Littler, CEO of Domainex. “We look forward to working together to efficiently and cost-
effectively develop a drug molecule for this important target. We also look forward to future
collaborations with Horizon on Domainex’s epigenetic pipeline in oncology and with the wide
number of projects that Domainex supports on behalf of its clients”
Kam Dhaliwal, Director of Business Development, Horizon said: “We are delighted that Domainex
has chosen to collaborate with Horizon on their lead program, and look forward to leveraging our
Discovery Toolbox and Oncology expertise to help guide the program.”
Horizon’s Discovery Toolbox is based on its proprietary precision rAAV-mediated genome editing
technology (GENESIS™), over 450 X-MAN human isogenic cell lines that more accurately model
patient genetics (known as “patients in a test tube”), and 2D and 3D phenotypic assays. The
Toolbox enables the recapitulation of the patient situation in vitro and allows screening of the
most important activated cancer genes and pathways found in patients, under conditions that
mimic the micro environment of the disease.
Financial terms of the agreement are not disclosed.
ENDS
Notes to Editors
Contacts:
At Horizon:
Kam Dhaliwal
Director of Business Development

2. Tel: +44 (0)1223 655 580
Email: Kam.Dhaliwal@horizondiscovery.com
Media enquiries for Horizon:
Katie Odgaard
Zyme Communications
Tel: +44 (0)7787 502 947
Email katie.odgaard@zymecommunications.com
At Domainex:
Joanne McCudden
Head of Business Development
Email: joanne.mccudden@domainex.co.uk
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. The Company’s
proprietary technology, GENESIS, is the world’s most precise genome editing technology. Using
GENESIS, 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 harnessed GENESIS to create over 450 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 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.
GENESIS and X-MAN are registered trademarks of Horizon Discovery Limited.
About Domainex Ltd. www.domainex.co.uk
Domainex uses unique and proprietary technologies to resolve common bottlenecks facing the
pharmaceutical and biotechnology industries in the post-genomic era. Major discovery 'gaps' exist
between the vast amount of genomic information that is now available, the accessibility of the
corresponding proteins for use in target validation and drug discovery, and the identification of
robust hits in a cost effective manner.
Founded in 2001, Domainex is a privately owned company based in Cambridge, UK. Domainex
has developed a discovery platform, which enables rapid progression of drug discovery projects
from novel target through to Candidate Drug by means of its Combinatorial Domain Hunting

3. technology, LeadBuilder virtual hit screening software, and its integrated approach to medicinal
and computational chemistry.
Domainex’s patented CDH technology enables the cloning and expression of soluble drug target
protein domains in E. coli, followed by the identification of those constructs that are able to bind a
ligand. Domainex has also developed LeadBuilder - a virtual screening approach for targets
which is specifically aimed at quickly identifying hit molecules that are ideally suited for further
development.
The experienced medicinal chemistry team has a proven track record in supporting biotech or
university groups by providing expertise to take hit compounds through lead optimization and on
to candidate selection. Three compounds to date arising from these collaborations are currently
in clinical evaluation, with two additional drugs in preclinical studies.
About The Institute of Cancer Research
(ICR) is one of the world’s most influential cancer research institutes. For more information visit
www.icr.ac.uk
Scientists and clinicians at the ICR are working every day to make a real impact on cancer
patients’ lives. Through its unique partnership with The Royal Marsden Hospital and ‘bench-to-
bedside’ approach, the ICR is able to create and deliver results in a way that other institutions
cannot. Together the two organisations are rated in the top four cancer centres globally.
The ICR has an outstanding record of achievement dating back more than 100 years. It provided
the first convincing evidence that DNA damage is the basic cause of cancer, laying the foundation
for the now universally accepted idea that cancer is a genetic disease. Today it leads the world at
isolating cancer-related genes and discovering new targeted drugs for personalised cancer
treatment. The Cancer Therapeutics Unit and Drug Development Unit at the ICR and The Royal
Marsden were recently honoured with the 2012 American Association for Cancer Research Team
Science Award for the “tremendous impact” of their preclinical and clinical studies.
As a college of the University of London, the ICR provides postgraduate higher education of
international distinction. It has charitable status and relies on support from partner organisations,
charities and the general public.
The ICR’s mission is to make the discoveries that defeat cancer.