Tango Adds $60M in CRISPR Hunt for Synthetically Lethal Cancer Drugs

Xconomy Boston — 

CRISPR is key to the cancer drugs that Tango Therapeutics is developing, but the startup isn’t out to edit disease-causing genes. Tango uses the technology as a tool for finding drug targets, in research that has yielded a pipeline of compounds. Now it has $60 million to continue that work.

The Series B round of financing announced Thursday was led by Boxer Capital of the Tavistock Group.

Cambridge, MA-based Tango is developing drugs intended to treat cancer by exploiting a genetic vulnerability in tumor cells. That vulnerability, a mutation lethal to the tumor if activated, isn’t readily targeted by conventional small molecule drugs. But these mutations rely on a second gene for their survival. Tango aims to trigger the genetic vulnerability with a workaround: hitting the second gene. The concept is called synthetic lethality.

Tango aims to find these synthetically lethal gene pairs. The company takes a panel of cell lines that have the genetic mutation that is lethal to a cancer cell, CEO Barbara Weber says. CRISPR is used to screen for the genes that, when drugged by a small molecule, trigger synthetic lethality.

“We couldn’t do this work without CRISPR,” Weber tells Xconomy. “The results you get with any other technology doing a partial or whole genome screen, you just get too many false positives.”

Tango now has a pipeline of five programs, the most advanced of which is being developed to address the loss of a tumor suppressor gene. With the new capital, Weber says Tango plans to continue the research to identify a lead compound and then conduct the preclinical studies that will enable the company to ask the FDA for the OK to proceed to tests in humans. Weber says she expects to have a drug candidate early next year and a filing seeking the go-ahead for clinical trials soon after.

Tango’s technology caught the eye of Gilead Sciences (NASDAQ: GILD), which began a drug discovery partnership with the startup two years ago. Weber says her company’s technology yields up to 20 discovery screens a year, which generate six to eight drug targets. That’s more than the company can advance on its own, which is one of the reasons Tango linked up with Gilead.

“We figure we can do four or five concurrent drug discovery programs but not more than that,” Weber says. “Instead of developing five at a time, we can develop, theoretically, 10 at a time—half of them with a partner.”

Synthetically lethal drugs have already reached the market from Clovis Oncology (NASDAQ: CLVS); Tesaro, which is now a part of GlaxoSmithKline (NYSE: GSK); and AstraZeneca (NYSE: AZN). The drugs from those companies target PARP, enzymes that cancer cells use to repair damage to their DNA. Biotech startups aiming to take synthetic lethality beyond PARP include Repare Therapeutics and Cyteir Therapeutics.

Tango emerged in 2017 with $55 million in financing from Third Rock Ventures, the venture capital firm that incubated the startup. The latest financing added Cormorant Asset Management and Casdin Capital as new investors. Those firms, and Boxer, are so-called crossover investors, which means they put their money into both private and public companies.

Crossover cash is typically viewed as a sign a company is preparing to go public. Weber acknowledges the association but says that’s not the case for Tango—at least not yet. Though the new investors are crossovers, Weber says they’re firms that have followed Tango since its early days, and they happen to also invest in public companies.

“For us, the earliest we would consider [an IPO] would be around the time of an [investigational new drug application] filing for our lead program,” Weber says.

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