The rapid growth of cancer cells actually damages them, leading them to rely on internal repair mechanisms. Scientists are finding ways to disrupt these repair features to fight the disease, and their research is leading to a growing crop of startups. Among them: Cambridge, MA-based Cyteir Therapeutics, which has just raised $29 million from Venrock, Celgene, and others.
Cyteir’s approach to treating cancer is based on research showing how cancer cells behave differently than healthy ones. The rapid growth of some cancers is associated with a protein called activation-induced cytidine deaminase (AID), says Cyteir co-founder and chief scientific officer Kevin Mills. That protein is present in small amounts in healthy cells, but it’s much more prevalent in cancer, he says.
Though AID helps cancers grow, it also damages their DNA, Mills says. To repair that damage, cancers use another protein called RAD51. A Cyteir cancer drug would interfere with that repair protein, limiting its ability to fix damaged DNA. As a result, AID activity is unchecked and destroys the cancer cell, Mills says.
Targeting genetic interactions in order to trigger a cell’s death is a concept called “synthetic lethality.” Drugs that use this approach to treat cancer have already reached the market. Boulder, CO-based Clovis Oncology (NASDAQ: CLVS) received FDA approval in 2016 for its drug rucaparib in ovarian cancer. Niraparib (Zejula), an ovarian cancer drug developed by Waltham, MA-based Tesaro (NASDAQ: TSRO), received the FDA’s nod nearly a year ago. AstraZeneca’s treatment, olaparib (Lynparza), is now approved for ovarian and breast cancers. All three drugs are so-called PARP inhibitors, named for the repair enzyme that they block.
Cyteir is the latest company to emerge with the goal of broadening synthetic lethality beyond PARP. Cambridge-based Tango Therapeutics unveiled a $55 million in funding last year to back its synthetic lethality research in cancer. Boston and Montreal-based Repare Therapeutics raised $68 million last year to support its work. Ideaya Biosciences, of South San Francisco and La Jolla, CA, which raised $46 million in 2016, is also in the mix.
Markus Renschler, Cyteir’s CEO, says his company’s approach could lead to treatments for blood cancers such as leukemia and lymphoma, as well as different types of solid tumors. He adds that lab tests show that Cyteir’s technology might boost the effects of a PARP-blocking drug, raising the possibility of its use in combination regimens. Renschler also says unlike its rivals, Cyteir is the first company to use this approach in autoimmune diseases. Lupus and type 1 diabetes are among the diseases that the company has been exploring, Renschler says.
Cyteir was founded in 2012, spun out of The Jackson Laboratory, a non-profit biomedical research lab in Maine. Renschler says Cyteir aims to start a blood cancer trial in mid-2019. The funding will also support additional preclinical work in autoimmune diseases.
Venrock led the Series B round of funding for Cyteir. Earlier investor Celgene (NASDAQ: CELG) also participated in the latest financing, joined by new investors Lightstone Ventures, and DROIA Oncology Ventures. Cyteir raised a $5.5 million Series A round in 2015.
Image of lymphoma tumor cells by the National Cancer Institute.