Cyteir reels in $29M to target DNA repair in cancer, autoimmune disease

Cyteir expects to start clinical trials of its small-molecule RAD51 inhibitors in 2019. (Nikolay Frolochkin)

Cyteir Therapeutics raised $29 million in series B funding, which will advance its lead program, small-molecule inhibitors of the DNA-repairing protein RAD51, into the clinic.

While the Cambridge, Massachusetts-based biotech said it is interested in both blood cancers and solid tumors, it did not indicate which indications it would look at in clinical trials slated to start in 2019. The funding will also propel its preclinical work in autoimmune disease, Cyteir said in a statement. It has highlighted lupus and multiple sclerosis as potential indications.

Cyteir’s platform operates on the theory that diseased cells have more DNA damage than healthy cells, making them rely more heavily on DNA repair for survival. It is designed to block the movement of RAD51 to and from areas of damage, reducing diseased cells’ ability to repair themselves and bringing about cell death in an effect called synthetic lethality.

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What sets its approach apart, the company says, is that it is targeting a “gain of function” in the enzyme activation-induced cytidine deaminase (AID), which damages DNA. Other synthetic lethality treatments, such as PARP inhibitors, take aim at DNA mutations that cause loss of function in specific genes.

“The advantages of this gain-of-function approach include potentially broader applicability, reduced side effects, and simpler, sensitive companion diagnostics for patient selection,” Cyteir said in the statement. This is because a gain in AID function happens in cancer cells and autoimmune disease, but not in healthy cells.

Preclinical studies have shown that disrupting the RAD51 transport cycle with Cyteir’s RAD51 inhibitors in AID-positive cancer cells is “effective and highly selective, leading to cancer cell death and tumor responses with minimal side effects,” Cyteir said.

"Not since the early PARP BRCA work have we seen as potent a synthetic lethal relationship as AID-RAD51," said Racquel Bracken, vice president at Venrock, which participated in the financing, alongside Celgene, Lightstone Ventures and DROIA Oncology Ventures. "Cyteir's highly respected and experienced team is leading the way in the discovery and development of groundbreaking new synthetic lethal therapies that have the potential to provide meaningful clinical benefit to patients across a spectrum of diseases."

Cyteir also picked up a new CEO: Markus Renschler, M.D., previously senior vice president and global head of hematology and oncology medical affairs at Celgene.