Syros, a Whitehead and Dana-Farber Spinoff, Snags $30M For Cancer

Xconomy Boston — 

Not many biotech startups are able to scrape together a $30 million venture round right out of the gate. But it’s happening today to a little company in Watertown, MA, with some edgy science from researchers at the Whitehead Institute and Dana-Farber Cancer Institute.

The startup, Syros Pharmaceuticals, is announcing today it has raised that large sum of $30 million in a Series A financing led by Arch Venture Partners and Flagship Ventures, and which included WuXi PharmaTech Corporate Venture Fund and undisclosed private investors.

This nine-employee company, which started operating in December, is emerging from stealth mode with a bang. It has not just big-name investors, but some big-name founders and executives, and a couple of publications describing its work in the journal Cell. The company is based on research by co-founders Richard Young of the Whitehead Institute and MIT; James “Jay” Bradner of Harvard Medical School, the Dana Farber Cancer Institute, and the Broad Institute; and Nathanael Gray of Harvard Medical School and the Dana Farber Cancer Institute. Nancy Simonian, the well-known former chief medical officer of Cambridge, MA-based Millennium Pharmaceuticals, has signed on as CEO, and Nobel laureate Phil Sharp of MIT has agreed to join the founders and investors on the Syros board.

Nancy Simonian, CEO of Syros Pharmaceuticals

The big idea here is that Syros believes it has found a novel way to attack disease by building on new insights into proteins that regulate how genes are expressed in the body. The researchers have identified what they call “super enhancers” —mainly transcription factors, kinases, and other enzymes—which are responsible for determining how an embryonic stem cell controls the genetic regions that tell it to become a skin cell, a muscle cell, a tumor cell, or something else. While many scientists use next-generation sequencing tools to look broadly at gene expression patterns or for variations like mutations that lead to disease, Syros believes it could have an unorthodox approach to drug development by focusing on these largely overlooked “super-enhancers” as drug targets.

There has been a push in biology for several years to look not just at genes, but at how genes are regulated, especially since the landmark publication of the public ENCODE consortium, which is redefining the way scientists think about regulation of gene expression. Syros believes it can go a step beyond those basic research findings, and that it has identified areas that are amenable to drug discovery, Simonian says. Syros’s “super enhancer” are few in number (only a couple hundred), they are different in that they are larger than other gene “enhancers,” and they (or their components) can be altered by conventional small-molecule drugs.

Some of these “super enhancers” are associated with genes that have been previously shown to drive disease, but some appear to be linked to many different downstream diseases, like forms of cancer, and they could end up being entirely new molecular targets that no one has gone after in the pharmaceutical industry, Simonian says. The company will focus on how these “super enhancers” give rise to disease states, she says, seeking to understand which ones the tumor cell depends on most to survive.

“It’s been really exciting,” Simonian says. “Over the last few years, people have been saying that all these really interesting things are coming out in biology, but ‘will people invest in them?’ A company like this is an example of people seeing the real promise, and putting some muscle behind it. It’s good for all of us in the sector.”

Robert Nelsen, the managing director at Arch Venture Partners, said earlier this week at an Xconomy event in Seattle that Syros is the kind of company that “tells us everything we thought we knew about transcription factors was wrong.” Nelsen got involved as a board member, and Arch is making a bet on it, because it represents a potentially important platform for new drug discovery, not an incremental innovation. Pharma acquirers appear to be indifferent toward incremental advances, but they still hunger for innovative platform discovery companies, like Cambridge, MA-based Agios Pharmaceuticals (cancer metabolism) and Cambridge, MA-based Moderna Therapeutics (messenger RNA therapies), Nelsen says.

Doug Cole, a general partner at Flagship Ventures in Cambridge, MA and a founding board member, added: “We have the sense that Syros is the kind of really discontinuous advance in understanding biology that takes place occasionally. It opens up significant new opportunities for therapeutic strategies.”

Syros, like a lot of startups, is staying pretty tight-lipped about its detailed plans, to keep competitors in the dark. The company isn’t disclosing what exact biological targets it is pursuing, and isn’t saying how far along its discovery programs are, although it does have small molecule compounds that it is seeking to optimize against certain targets, Cole says. The company intends to develop cancer drugs through its internal R&D, and it will consider out-licensing the drug development rights for other diseases, Simonian says.

The team at Syros is getting started with technology licenses from Young’s group at the Whitehead Institute and from Bradner’s group at the Dana-Farber Cancer Institute.

The risk, as with any biotech company at such an early stage, is all about the things researchers don’t know. Since it’s not going after already validated targets, it’s possible that some of the targets might be too frequently expressed in healthy cells, or the drug candidates made to hit them could cause some other form of toxicity.

While Simonian brings a wealth of experience and industry contacts to the CEO role, the majority of Syros’s early team—five of the first nine—are former graduate students and postdocs who worked under the founders, Simonian says. The senior management team includes Scott Rakestraw (formerly of Altus Pharmaceuticals) as chief business officer; Gregg Beloff (formerly of Archemix) as chief financial officer; Christian Fritz (formerly of Infinity Pharmaceuticals) as the vice president of biology, and Kevin Sprott (formerly of Verastem and Ironwood Pharmaceuticals), as the senior director of chemistry.

The name of the company, for those curious, appears to have nothing to do with the science. It comes from the name of a Greek island. The VCs at Arch and Flagship liked it, Cole says, because they had good luck with another company named after a Greek island—Agios Pharmaceuticals.