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Horizon Discovery Ltd. Launches SyntheTx Partnership Program to Identify Novel Targets for Cancer Therapeutics



10/5/2012 11:08:12 AM

CAMBRIDGE, England, and CAMBRIDGE, Mass., Oct. 4, 2012 /PRNewswire/ -- Horizon Discovery Ltd (Horizon), a leading provider of research tools to support the development of personalized medicines, and H3 Biomedicine Inc. today announced the launch of SyntheTx, a technology partnership program aiming to become a major supplier of novel oncology targets and early-stage drug discovery programs to the pharmaceutical industry. H3 Biomedicine, a biopharmaceutical company specializing in the discovery and development of targeted patient-specific cancer treatments, is the first partner for the program. Additional biotechnology and/or pharmaceutical partners will be sought in the first 12 to 18 months of the program. Professor Alan Ashworth, Professor of Molecular Biology at the Institute of Cancer research (ICR) and pioneer of synthetic lethality screening, will join Horizon's Scientific Advisory Board to provide oversight of the program.

(Logo: http://photos.prnewswire.com/prnh/20120430/NY96379LOGO )

Horizon and H3 Biomedicine will screen up to 50 currently "undruggable" but key cancer-driving genotypes, with the aim of identifying a range of targets that will be optioned by Horizon and H3 for further development. Any targets not optioned by H3 Biomedicine or Horizon will be made available on commercial terms to the pharmaceutical industry at the end of the program. The program will also capitalize on Horizon's precision genome editing technology (GENESIS) to perform rigorous target validation and to promote its partners' capabilities around early lead molecule generation.

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. In a synthetic lethal genetic screen, it is necessary to begin with a known mutation that does not cause cell death, then systematically test other mutations to determine which combination confers lethality. Synthetic lethal screens have demonstrated potential in oncology, as these pairs of mutations could be used to selectively kill cancer cells, but leave normal cells relatively unharmed. Targets selected by the SyntheTx program will have been shown to exhibit synthetic lethality with or co-dependency on a specific genotype.

"Proof-of-concept synthetic lethal screens have shown significant promise in uncovering novel targets, but these studies have so far been unwieldy, difficult to understand and cannot represent all genes of interest," said Dr. Chris Torrance, Chief Scientific Officer, Horizon. "Isogenic disease models created using our GENESIS gene editing technology will for the first time allow large scale, timely and systematic synthetic lethality screens, incorporating any patient-relevant genetic context."

SyntheTx brings together Horizon's ability to generate human isogenic cell lines that accurately replicate specific genetic defects present within defined cancer patient populations, with the high-throughput RNAi and bioinformatics technology platforms of Horizon and H3 Biomedicine. Utilizing Horizon's ability to reproduce tumor microenvironment conditions to reveal the genetic dependencies of cancer cells in vitro, SyntheTx aims to uncover points of vulnerability in the genomes of the cancer cell lines screened, and then confirm these vulnerabilities in wider cell panels.

This program of 'de-orphaning' the cancer genome is designed to provide a vast number of new druggable synthetic lethal targets with clear patient stratification strategies for future progression by the partners.

Professor Alan Ashworth commented: "My research has been dedicated to investigating the causes, and methods of prevention, diagnosis and treatment of cancer. By discovering new synthetic lethal targets with SyntheTx, significant advances in the treatment of cancer will be possible."

Dr. Markus Warmuth, Chief Executive Officer, H3 Biomedicine, said: "A key goal of H3 Biomedicine is to bring to the clinic lead molecules based upon highly validated and novel drug targets. Innovative and open collaboration concepts are an important part of our mission to deliver effective cancer medicines to patients in need. SyntheTx will be an exciting way to capitalize on the new insights provided by cancer genome sequencing efforts."

SyntheTx' business model will seek commercialization at three defined stages: early partnering of putative targets in conjunction with rigorous biological validation services; partnering of validated targets; and partnering of small molecule lead discovery programs with either in vitro or in vivo proof-of-concept.

About SyntheTx

SyntheTx is a technology partnership founded in 2012, initially between Horizon Discovery Limited (Horizon) and H3 Biomedicine (H3), with Professor Alan Ashworth, Professor of Molecular Biology at the Institute of Cancer Research (ICR), providing key scientific input / oversight.

SyntheTx is focused on rapidly generating a pipeline of targets to classically undruggable cancer genes, especially those that elicit robust "synthetic lethal" events in cancer-specific genetic backgrounds, thereby de-orphaning the cancer genome. The group aims to become a leading supplier of novel oncology targets and early-stage drug discovery programs to the pharmaceutical industry.

SyntheTx will utilize Horizon's precision genome editing technology (GENESIS) and genetically-defined, patient-relevant X-MAN isogenic human cell lines, along with high throughput functional genomics platforms and early lead-molecule generation capabilities of Horizon and its partners.

SyntheTx operates a capital-efficient, flexible business model that achieves commercialization at three defined stages: early partnering of putative targets in conjunction with rigorous biological validation services; partnering of validated targets; and partnering of small molecule lead discovery programs with either in vitro or in vivo proof-of-concept.

About Horizon Discovery http://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, the Company's proprietary rAAV gene-editing technology, 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 400 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.

GENESIS and X-MAN are registered trademarks of Horizon Discovery Limited.

About H3 Biomedicine Inc. http://www.h3biomedicine.com/default.asp

H3 Biomedicine, a Cambridge, Massachusetts-based biopharmaceutical company, specializes in the discovery and development of oncology treatments. Using modern synthetic chemistry, chemical biology and human genetics, the company seeks to bring the next generation of cancer treatments to market with the goal of improving the lives of patients.

SOURCE H3 Biomedicine Inc.


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