Horizon and H3 Biomedicine Kick Off SyntheTx Program

Horizon Discovery Ltd. and H3 Biomedicine Inc. have announced the launch of SyntheTx, a new technology partnership program that is intended to become a leading supplier of novel oncology targets and early-stage drug discovery programs for the pharmaceutical industry. H3 Biomedicine represents the first partner for the program, and additional partners will be evaluated in the first 12 to 18 months of the program. Prof. Alan Ashworth, professor of molecular biology at the Institute of Cancer Research, will join the ranks of Horizon’s scientific advisory board as an overseer for the program.

“A key goal of H3 Biomedicine is to bring to the clinic lead molecules based upon highly validated and novel drug targets,” Dr. Markus Warmuth, CEO of H3 Biomedicine, said in a press release. “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.”

The business model of SyntheTx will be to pursue commercialization at three 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.” Horizon brings to SyntheTx its human isogenic cell lines, which accurately replicate specific genetic defects that present in defined cancer patient populations, and the program combines both companies’ high-throughput RNAi and bioinformatics technology platforms. The program will seek 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 key cancer-driving genotypes currently considered to be undruggable in hopes of determining targets to be optioned by the companies for development. Any targets that Horizon and H3 Biomedicine do not option will be available on commercial terms for the pharmaceutical industry at the end of the program. GENESIS, Horizon’s precision genome-editing technology, will be used in target validation.

“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,” Dr. Chris Torrance, chief scientific officer at Horizon, said in a statement. “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.”

Synthetic lethality is found where the combination of mutations in two genes or more results in cell death, and yet a mutation in just 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 and then test other mutations to identify a combination that results in lethality. These screens have been shown to have potential in oncology. All targets chosen in the SyntheTx program will demonstrate synthetic lethality with or co-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, a pioneer in the field of synthetic lethality screening. “By discovering new synthetic lethal targets with SyntheTx, significant advances in the treatment of cancer will be possible.”