After 18 months being incubated by Versant Ventures, upstart Repare Therapeutics has emerged from stealth mode with an impressive $68 million, backing from Celgene and some big-name execs.
The Montreal and Cambridge, Massachusetts, biotech saw founding investor Versant Ventures co-lead the series A round with MPM Capital. They were also joined by other syndicate investors including FTQ, Celgene and BDC Ventures.
The biotech’s focus is on its CRISPR-enabled “synthetic lethality,” the interaction between two genes that causes cell death when both are inactivated. In cancer cells, one of these genes is inactivated by mutation; the other will be inactivated by a drug.
This leaves normal cells largely unaffected, with the potential to greatly boost antitumor efficacy and lower side effects.
Repare and its founders say they have developed large-scale and new methods for discovering additional drug targets that, when inhibited, may induce this synthetic lethality.
The first FDA-approved example of this type of synthetic lethality in cancer are PARP inhibitors for BRCA-mutant ovarian cancer, which include AstraZeneca’s Lynparza (olaparib) and, more recently, Tesaro’s Zejula (niraparib).
After spending 18 months quietly working under Versant’s wing, the biotech has come out into the open and says it has “identified several promising oncology targets and moved multiple programs into preclinical development.”
Repare’s first disclosed program targets DNA-directed DNA polymerase theta (PolQ), a central component of a pathway that repairs double-strand breaks in cancer cells. New York University School of Medicine has licensed to Repare exclusive rights to drug discovery work targeting PolQ, developed by Agnel Sfeir, Ph.D., with the support of NYU's Office of Therapeutics Alliances. This polymerase is highly expressed in ovarian, breast and a number of other cancers. The first human test for its leading compound is slated for 2019.
Founders Sfeir, Daniel Durocher, Ph.D., senior scientist at the Lunenfeld-Tanenbaum Research Institute in Canada, and Frank Sicheri, Ph.D., a professor in the departments of biochemistry and molecular genetics at the University of Toronto, played “instrumental roles in the company’s formation and growth in partnership with Versant,” the VC says.
“Versant’s commitment to and confidence in Repare’s distinct science has enabled the company to build the team, operations and initial programs away from the spotlight,” said Repare CEO and Versant exec Lloyd Segal in a statement. “With the added leadership of MPM and this syndicate, we are financed to achieve our goal of testing our multiple new, precision oncology therapeutics in a clinical setting.”
Repare’s management team also includes R&D head Michael Zinda, Ph.D., who built and led AstraZeneca’s Oncology iMed Bioscience group in Boston; and VP of discovery Cameron Black, Ph.D., an 18-year leader of Merck Frosst’s medicinal chemistry efforts.
The biotech has a 20-member team based in Montreal and Boston, but Jerel Davis, Ph.D., a managing director at Versant and a Repare board member, told FierceBiotech that this isn’t a virtual company: “Repare has a headquarters building in Montreal and a satellite office in Boston,” he explains. “In the next 12-18 months, Repare plans to continue to grow its headcount to advance multiple programs internally.”
The $68 million for a series A is a big achievement, with Davis saying that this “was a significantly oversubscribed round.” Why? “There are a few reasons for the size of the round and high-levels of interest in Repare. The success of PARPs and multiple other players in the space proves the notion that several companies and compounds are likely to make it to market and in a market as unfortunately large as cancer, there’s a lot of opportunity for innovative new products that can improve patient outcomes.”
He says that Repare has “several distinguishing elements,” including its programs and proprietary platform for CRISPR SL screening and SBDD. “The field itself is moving incredibly rapidly, and Repare, Versant and the rest of the syndicate have strong conviction and want to be able to progress multiple programs in parallel and to continue to industrialize the company’s platform.”
Though very early stage, Davis says the biotech is already seeing potential for combination trials in the future with drugs such as PARPs and/or checkpoint inhibitors.
“There already are striking data for PARP inhibitors in combination with checkpoint inhibitors. Since Repare is working on molecules that, like PARPs, induce synthetic lethality, there will be multiple opportunities to combine with a host of promising marketed agents both outside and inside the immuno-oncology field.”
The biotech joins another startup that launched back in March, Tango, which is also focused on synthetic lethality. It got off a $55 million investment boost from VC Third Rock Ventures, with 10 staffers based in Cambridge, Massachusetts, and is also buoyed by the recent interest in PARP development.