Big Pharma VC firms put $11M in seed funds behind cancer startup with bold vision
The venture arms of three Big Pharmas have jumped in to seed a Swiss cancer startup with a bold twist on targeted therapy that, the founders say, could have effects on virtually every type of cancer.
Novartis Ventures, Pfizer Ventures and Merck’s M Ventures, along with Omega and LSP, have seeded FoRx Therapeutics with €10 million ($11 million). The biotech, founded by synthetic biology pioneer Thanos Halazonetis, will look to target and disrupt a DNA repair mechanism he discovered several years ago and that, he said, almost all cancers rely on to proliferate.
“This is a feature of almost all cancers,” Halazonetis told Endpoints News. “Normal cells are not affected.”
The company relies on a concept known as synthetic lethality. Generally, that refers to when a particular mutation helps gives rise to cancer but also makes that cancer reliant on certain processes that normal cells don’t rely on. The most famous example is PARP inhibitor. Patients with mutations in a DNA repair enzyme called BRCA1 or BRCA2 are prone to cancer. Because those cancer cells, though, are missing one functioning DNA repair enzyme, they become reliant on a different one, called PARP, to properly replicate.
New biotechs, such as Third Rock Venture’s Tango Therapeutics, are using technology like CRISPR screens to find new pairs of genes that are similarly linked.
FoRx, though, is going after a pathway they say virtually all cancer cells rely on, called the break-induced replication pathway. Basically, normal healthy cells begin DNA replication at precise points on the double helix. Cancers with oncogenes, though, in their rush to propagate as fast as possible, start at the wrong point. Strands that begin copying themselves at the wrong point eventually bump up against the rest of the transcriptional machinery, collisions that interfere with their ability to copy.
“It’s like someone trying to run too fast and they trip and fall down,” Halazonetis said.
Cancer cells can survive this, though, because all cells have proteins to fix the damage wrought when DNA repairs at the wrong starting point. FoRx plans to block those proteins. Halazonetis said this should kill cancer cells but should have little effect on healthy cells, who rarely need to use this method of repairing their DNA.
“As far as we know, there are no other biotechs focusing on this,” Vincent Ossipow, a partner at Omega and a FoRx board member, told Endpoints.
Ossipow compared this investment to Omega’s past efforts to get in on the ground floor of new cancer research, including with bispecific antibodies and oncolytic viruses.
Halazonetis first published on the discovery of the pathway in Nature in 2005, and further on how it works and might be drugged in 2014 in Science, and again in Nature in 2018. Because the pathway is used by virtually all cancers, Halazonetis suggested that it should not lead to the resistance most other targeted cancer therapies eventually give rise to.
The specific compounds the FoRx might use, though, remain under wraps. They hope to bounce a target in the next 18-24 months and be in the clinic 12-18 months after that. They will go first after cancers that lack good targeted options, such as colon cancer, with the goal of becoming leaders in synthetic lethality.
“It’s a hot but not yet crowded landscape,” Therese Maria Liechtenstein of M Ventures told Endpoints. “Thanos is a pioneer.”