The Swiss biotech FoRx Therapeutics has raised an impressive €10M in seed funding to develop a new generation of drugs that target DNA repair in cancer cells.
The drugs will block a DNA repair process called break-induced replication, which was discovered by the company’s scientific founder Thanos Halazonetis. This process is used by cancer cells to prevent DNA damage caused by a phenomenon known as DNA replication stress, which happens when they are preparing to replicate themselves.
Halazonetis told me that “cancer cells are more dependent on break-induced replication for their survival than normal cells and, without this repair pathway, replicating cancer cells die.”
He added that the break-induced replication DNA repair pathway in tumor cells is barely functional in healthy cells.
“Therapeutic candidates [targeting break-induced replication] would thus be expected to have a highly differentiated safety profile and very high specificity for cancer cells,” Halazonetis said.
DNA replication stress is ubiquitous in cancers, and not associated with any specific mutations. This means the drugs could take on a wide range of tumor types.
This also presents a potential advantage over other anti-cancer drugs currently targeting DNA damage repair. These drugs are often only effective in cancers that have specific genetic mutations, such as the BRCA1 and BRCA2 mutations that occur in breast and ovarian cancer. A good example is AstraZeneca and Merck’s approved drug Lynparza, which inhibits a protein called PARP that is required for DNA repair. Lynparza’s approved use was expanded to the first-line treatment of ovarian cancer in the EU last year.
Halazonetis said that the €10M, raised in a financing round led by M Ventures (the venture capital arm of Merck), Novartis Venture Fund, and Omega Funds, and also included Pfizer Ventures and Life Sciences Partners, will be used to perform screening assays and optimize lead drug candidates for taking into clinical trials.
FoRx believes that its therapeutics could be used to treat cancers with high levels of DNA replication stress, including colorectal cancers, therapy-resistant melanoma, and ovarian cancers.
Although FoRx is targeting a novel aspect of DNA repair within tumors, there is a lot of buzz surrounding the field as a whole, according to Niall Martin, CEO of UK Biotech Artios Pharma. Artios raised a €73M Series B in August 2018 to develop a drug that targets a different aspect of DNA replication repair.
And recent research suggests the use of DNA replication repair inhibitors could extend beyond the field of oncology. The Danish company Oncology Venture has announced that its PARP inhibitor, which is phase II trials for ovarian cancer, may be active against the coronavirus that causes Covid-19.
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