CAMBRIDGE, United Kingdom—Horizon Discovery Ltd. and H3Biomedicine Inc. have announced the launch of SyntheTx, a new technologypartnership program that is intended to become a leading supplier of noveloncology targets and early-stage drug discovery programs for the pharmaceuticalindustry. H3 Biomedicine represents the first partner for the program, andadditional partners will be evaluated in the first 12 to 18 months of theprogram. Prof. Alan Ashworth, professor of molecular biology at the Instituteof Cancer Research, will join the ranks of Horizon's scientific advisory boardas an overseer for the program.
"A key goal of H3 Biomedicine is to bring to the clinic leadmolecules based upon highly validated and novel drug targets," Dr. MarkusWarmuth, CEO of H3 Biomedicine, said in a press release. "Innovative and opencollaboration concepts are an important part of our mission – to delivereffective cancer medicines to patients in need. SyntheTx will be an excitingway to capitalize on the new insights provided by cancer genome sequencingefforts."
The business model of SyntheTx will be to pursuecommercialization at three stages: "early partnering of putative targets inconjunction with rigorous biological validation services, partnering of validatedtargets and partnering of small-molecule lead discovery programs with either in-vitro or in-vivo proof of concept." Horizon brings to SyntheTx its human isogenic celllines, which accurately replicate specific genetic defects that present indefined cancer patient populations, and the program combines both companies'high-throughput RNAi and bioinformatics technology platforms. The program willseek to discover vulnerable sites in the genomes of screened cancer cell lines,and confirm the vulnerabilities in wider cell panels.
Horizon and H3 Biomedicine will screen up to 50 keycancer-driving genotypes currently considered to be undruggable in hopes ofdetermining targets to be optioned by the companies for development. Anytargets that Horizon and H3 Biomedicine do not option will be available oncommercial terms for the pharmaceutical industry at the end of the program.GENESIS, Horizon's precision genome-editing technology, will be used in targetvalidation.
"Proof-of-concept synthetic lethal screens have shownsignificant promise in uncovering novel targets, but these studies have so farbeen unwieldy, difficult to understand and cannot represent all genes ofinterest," Dr. Chris Torrance, chief scientific officer at Horizon, said in astatement. "Isogenic disease models created using our GENESIS gene editingtechnology will for the first time allow large scale, timely and systematicsynthetic lethality screens, incorporating any patient-relevant geneticcontext."
Synthetic lethality is found where the combination ofmutations in two genes or more results in cell death, and yet a mutation injust one of the genes does not. In a synthetic lethal genetic screen,researchers begin with a known mutation that does not lead to cell death andthen test other mutations to identify a combination that results in lethality.These screens have been shown to have potential in oncology. All targets chosenin the SyntheTx program will demonstrate synthetic lethality with orco-dependency on a specific genotype.
"My research has been dedicated to investigating the causes,and methods of prevention, diagnosis and treatment of cancer," said Ashworth, apioneer in the field of synthetic lethality screening. "By discovering newsynthetic lethal targets with SyntheTx, significant advances in the treatmentof cancer will be possible."
SOURCE: Horizon press release
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