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Start-ups

Relay raises $400 million to wrangle protein motion

The influx of cash will allow the biotech firm to open new offices, expand staff, and enhance its technology platform

by Lisa M. Jarvis
December 20, 2018

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Credit: Relay Therapeutics/C&EN/Shutterstock
Taking movies: Relay uses new technologies to create movies, rather than snapshots, of proteins.

Relay Therapeutics, which aims to take down difficult cancer drug targets by combining powerful computational methods with emerging lab tools, has raised a whopping $400 million in its third formal financing round. The privately held company says it is the biggest Series C in biotech industry history.

Third Rock Ventures spent two years incubating Relay, which was a 2017 pick for C&EN’s 10 Start-ups to Watch, before putting $57 million into the firm in 2016. Those early years were spent developing a range of technologies that, taken together, allows researchers to get a more sophisticated view of proteins.

When designing small molecules to hook into pockets on proteins, drug hunters have traditionally relied on a snapshot generated by X-ray crystallography. But in real life, proteins flex, bend, and jiggle as they interact with partners or are modified by other molecules. Relay is trying to capture that motion, an approach it says can reveal new toeholds for oncology targets that have long been intractable.

To get a movie of proteins in their natural state, the company relies on technologies that until recently didn’t exist or had yet to evolve to the point where they could be used efficiently and affordably in drug discovery. In addition to supercomputing power, those new technologies include cryoelectron microscopy, room temperature crystallography, DNA-encoded libraries, and high throughput second-generational harmonic technology—a way of capturing conformational changes that happen when a ligand docks to a protein.

By watching a protein’s large, conformational movements, Relay scientists can figure out how specific changes relate to the protein’s function and design a small molecule to control it, says Relay’s CEO Sanjiv Patel. Those movies also uncover “with much greater detail potential binding sites for medicines,” he adds, including allosteric sites—pockets outside of a protein’s active site. And in the past two years, “our scientists have been able to make great progress in stabilizing some of the most notoriously difficult-to-address proteins” in the cancer field.

Between Third Rock’s initial investment, a Series B round raised last year, and today’s cash, Relay now has more than a half billion to play with. So where will all that money go? Relay’s Patel points to five areas: expanding the company’s early-stage oncology drug discovery activities; putting compounds into the clinic; continuing to build its computational capabilities and artificial intelligence tools; expanding its workforce from 70 people to 100 in 2019; and moving into a larger space in Cambridge, Massachusetts.

Although a growing number of private biotech firms developing technology platforms have in recent years raised significant cash from venture capital firms, their drug candidates have generally been in, or at least on the cusp of clinical trials. Relay, by contract, still isn’t providing details about what proteins or specific types of cancer it is pursuing or when it might put one of its compounds into human studies. “By any standards, that’s a huge amount of money for a very early company,” notes Don Nicholson, former CEO of Nimbus Therapeutics, which also used advanced computational technology to discover drugs for difficult protein targets. “Good for them, but pretty remarkable.”

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