Horizon Discovery launches SyntheTx Partnership Program to identify novel targets for cancer

Horizon Discovery Ltd (Horizon), a leading provider of research tools to support the development of personalized medicines, and H3 Biomedicine Inc. 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.

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.