Over the past 18 months, the growing team at Repare Therapeutics has been quietly setting up shop in Versant Ventures’ discovery ops and focusing on synthetic lethality — the therapeutic interplay between genetic mutations and cancer. Using CRISPR gene editing tech as an interrogation tool, they’ve been playing with well known targets like p53 and BRCA1 to find out how they conspire with other mutations in the destruction of a malignancy, following the trail of lesions in the pursuit of new therapies that can work in the same fundamental way those PARP inhibitors you’ve been hearing so much about can fight cancer.
The goal was to master synthetic lethality and identify the first couple of targets to go after in the clinic. They lined up their team, now at 20, licensed in discovery work from NYU on a polymerase implicated in numerous cancers, and today will come out of stealth mode with a $68 million round and at least a four-year runway with plans to start tackling clinical work in late 2019.
Their first program involves DNA-directed DNA polymerase theta — PolQ — included in a pathway that repairs double-strand breaks in cancer cells. And while they have a ways to go before they begin human studies, the investors are sending a message that the amount of cash they’re betting on Repare indicates a high level of confidence for their longterm success.
“In terms of the incubation period,” says Jerel Davis, managing director at Versant, “this company is deceptively mature.”
“The time we’ve been able to spend in stealth allowed us to build the company out of the spotlight,” says CEO Lloyd Segal. In Montreal they have developed their medicinal chemistry team under Cameron Black, the former head of chemistry at Merck Frosst who joined a little more than a year ago. And when Vertex recently shut down in Montreal, they swooped in, grabbing an experienced team with a long track record of working together.
Within hours of the shutdown, they had 13 new recruits out of 14 offers.
R&D head Michael Zinda, who led AstraZeneca Oncology iMed Bioscience group in Boston, is heading up the other group in Cambridge, MA.
Versant has gathered an impressive group of marquee investors to back their upstart. MPM Capital came in alongside as the lead investor on the Series A, with Celgene’s Swiss office taking part along with FTQ and BDC Ventures.
“We could have taken more money,” Segal tells me. “We had more than that on the table. But we believed that was the kind of money that we hope will take two compounds into the clinic in late ’19 or early 2020.”
Versant had a front row seat on some of the early work on synthetic lethality at Clovis while it was working on PARP, says Davis. “This is a field we know and our conviction is that PARP is the tip off the iceberg.”
Repare has the platform that they plan to use to map out some of the rest of the unexplored territory.
Even without R&D partners Segal feels that he has enough cash to make their way through at least the first 4 years. Add in the prospect of some major league players coming in to partner on key prospects, and that runway will stretch further. If it all plays out according to plan, Segal adds, this will be their last venture raise.
It’s an ambitious plan, with some stellar scientific advisers ready to leaned guidance. The full scientific advisory board includes:
– Samuel Aparicio, professor in the department of pathology and laboratory medicine at the University of British Columbia.
– Jim Carmichael, head of the protein homeostasis thematic center of excellence at Celgene. He previously was UK regional director of medical science at AstraZeneca following its acquisition of KuDOS, where he was CMO and responsible for clinical development of olaparib.
– Ronny Drapkin, director of the Penn Ovarian Cancer Research Center and director of gynecologic cancer research at the University of Pennsylvania.
– Laurie Glimcher, president and CEO of the Dana-Farber Cancer Institute.
– Mark Pegram, director of the breast cancer oncology program at Stanford Women’s Cancer Center and co-director of Stanford’s molecular therapeutics program.
– Richard Wood, professor of molecular biology at the University of Texas MD Anderson Cancer Center.
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