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

Revolution Medicines CEO Dr. Mark Goldsmith

Revolution Medicines is developing technology it believes can do evolution one better, improving on naturally occurring compounds to transform promising but raw molecules into discrete drug candidates. And, with the help of $45 million from Third Rock Ventures, the biotech is first setting its sights on a pedigreed antifungal therapy.

The company's platform stems from the work of Martin Burke, Revolution cofounder and chemistry professor at the University of Illinois at Urbana-Champaign. Burke's lab invented a proprietary method of taking complex natural chemicals and breaking down their component parts, allowing researchers to construct optimized versions using the building blocks of their reference compounds. Recognizing the promise of such an approach, Third Rock stepped in and licensed the technology from U of I, bringing Burke into the fold and launching Revolution with firm partner and biopharma veteran Dr. Mark Goldsmith at the helm.

With the technology, Revolution can Xerox molecules of therapeutic merit and leave out the bits that lead to toxicity or poor specificity, Burke said, all the while relying on the evolutionary process that formed each compound in the first place. And that gives Revolution "a billion-year head start" on therapeutic development, he said.

The company's first target is a well-understood antifungal agent called amphotericin B, a powerful natural compound with 50 years of clinical use that has somehow avoided generating significant drug resistance. The problem with amphotericin B, however, is its history of major kidney side effects, Burke said, leading physicians and patients to nickname it "amphoterrible."

That's where Revolution's platform comes in, Goldsmith said, as the biotech believes it has figured out how to synthesize a new version of the compound that omits the molecular components responsible for its nasty toxicity.

Now, with $45 million to pay its way, Revolution is focused on two goals, Goldsmith said: ironing out Burke's technology to enable industrial-scale drug development and picking a few lead antifungal candidates from the swath of compounds it brought in through the U of I deal.

And that's just the first phase of Revolution's plan, Goldsmith said. Once the biotech has a lead product candidate rolling in the antifungal space, it plans to begin work in antibiotics, testing whether Burke's discovery can help craft treatments that skirt the scourge of drug resistance. From there, Revolution plans to set out on human targets, pointing out that more than half of all approved drugs are derived from natural compounds and betting its platform can spur some innovation.

"There's a strong precedent for and validation of the concept that natural products can modulate human disease targets, even though nature may have selected them for some other purpose," Goldsmith said.

Alongside Burke and Goldsmith, Third Rock has recruited David Pompliano, former head of infectious disease R&D at Merck ($MRK) and GlaxoSmithKline ($GSK), to serve as chief scientific officer. The firm's Neil Exter, who helped get bluebird bio ($BLUE) and Foundation Medicine ($FMI) off the ground, is on hand as chief business officer, and Third Rock Partner Alexis Borisy is on the biotech's board.

- read the announcement