Revolution Medicines

Revolution CEO Dr. Mark Goldsmith

Revolution Medicines
Doing nature one better

CEO: Dr. Mark Goldsmith
Based: Redwood City, CA
Founded: 2015
Clinical focus: Antifungal therapies
Company website

The scoop: As drug discovery platforms go, none is older than evolution. Over billions of years, the slow march of life has brought about natural agents gradually selected for their ability to modulate certain biological processes. But evolution's products, however elegant, don't often come out of the gate with the tolerability and specificity required for medicinal use. That's where startup Revolution Medicines comes in, developing a technology through which it can break down natural compounds to their composite parts, apply some chemistry know-how and then reassemble them into usable drugs.

What makes Revolution Medicines Fierce: Based on the work of Martin Burke, a chemistry professor at the University of Illinois at Urbana-Champaign, the company is pressing forward with a platform that aims to do evolution one better. Burke's discoveries allow Revolution to take molecules of therapeutic merit and create copies that excise the parts that lead to toxicity or poor targeting, the company said, all the while relying on the evolutionary processes that formed each compound in the first place.

Many biological targets remain effectively undruggable through traditional synthetic chemistry, Revolution CEO Dr. Mark Goldsmith said, and the natural products that might modulate them have long been too complex to be fashioned into therapies. Revolution, with its platform, believes it can bridge that gap.

The company's first focus is a well-understood antifungal agent called amphotericin B, a powerful natural compound with 50 years of clinical use that has to date avoided generating significant drug resistance. The problem with amphotericin B, however, is its history of major kidney side effects. Revolution is now at work on synthesizing a new version of the compound that omits the molecular components responsible for its nasty toxicity, and the company expects to identify a development candidate soon.

Beyond the antifungal space, Revolution has begun early-stage programs for antibacterial and mammalian targets, the next steps for a development platform Goldsmith said has wide-ranging applications.

Revolution is a product of the well-regarded startup engine at Third Rock Ventures, which traditionally works by identifying promising technologies, assembling talent around them and then founding a company with the goal of building a product engine rather than going all-in on a single asset. Revolution got off the ground in February with $45 million from Third Rock, and it counts many of the firm's usual cast (including Goldsmith) among its executives and board members. Third Rock's Neil Exter, who helped get bluebird bio ($BLUE) and Foundation Medicine ($FMI) up and running, is on hand as chief business officer, and firm partner Alexis Borisy is on the biotech's board. Goldsmith is back for his fourth stint at the helm of a Third Rock-founded biotech after stops at Nurix, Global Blood Therapeutics ($GBT) and 2008 Fierce 15 honoree Constellation Pharmaceuticals.

Now, to follow through on the promise of Burke's work, Revolution is quickly expanding its ranks. After launching with about four employees, the company now has 18 workers and a fully operational research lab. In March, Revolution brought in Dr. Carole Sable, a veteran of Scynexis ($SCYX) and Merck ($MRK), to serve as chief medical officer; and Luan Wilfong, who previously worked at Gilead Sciences ($GILD), to serve as vice president of human resources as the company builds out its team.

The goal for Revolution is to at once advance its programs into clinical trials and perfect its guiding approach of repurposing natural products, two intertwined tasks Goldsmith said are well within the biotech's wheelhouse. The company may look to partner up with larger drugmakers as it illuminates more applications for its technology, but for now Revolution is focused on making its name through in-house R&D.

"We'd like to be recognized as the company that can tackle a target through compounds that nature has handed us, with the best ability to recognize those compounds and optimize them to become drugs," Goldsmith said. "That's what we seek to demonstrate ourselves as, and there's a lot of work ahead to fulfill that."

Investor: Third Rock Ventures

For more:
Third Rock starts a $45M Revolution to soup up natural remedies

-- Damian Garde (email | Twitter)

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