Nature’s been a fantastically bountiful source of medicine, sure. But turns out the drug compounds found secreted by a sea sponge or on the underside of a log have very elaborate chemical structures. When used for unintended purposes like, say, treating humans, these compounds can both help and harm.
Third Rock Ventures just funneled an impressive $45 million to launch a new Bay Area company, Revolution Medicines, that fine tunes nature’s approach to developing drugs. The idea is to modify naturally occurring drugs to deliver the optimal pharmaceutical benefit – without the negative side effects. Revolution Medicines is, after all, a portmanteau of the words “redesigning evolution,” CEO Mark Goldsmith said.
Turns out these complex molecules found in nature can actually be simplified into modular structures, which can be pieced back together to make a drug of choice.
When Investment Rhymes with Canada
Canada has a proud history of achievement in the areas of science and technology, and the field of biomanufacturing and life sciences is no exception.
The technology comes from chemist Martin Burke at the University of Illinois, who has formulated just-right reaction conditions to make this work. This process was published in Nature a year ago, showing how many drug structures can be built like a piece of Ikea furniture:
The inherent modularity of polypeptides, oligonucleotides and oligosaccharides has been harnessed to achieve generalized synthesis platforms. Importantly, like these other targets, most small-molecule natural products are biosynthesized via iterative coupling of bifunctional building blocks. This suggests that many small molecules also possess inherent modularity commensurate with systematic building block-based construction.
The platform allows scientists to deconstruct complex, naturally occurring compounds and break them down into simple building blocks – “like Legos,” Goldsmith says. Once the chaff’s been cut, these molecular subunits can then be reassembled – snapped together with carbon-carbon bonds – into more effective versions of the drug. Here’s Burke describing how it works:
Take Burke’s work with amphotericin B – a potent antifungal that hasn’t succumbed to drug resistance in the past 50 years. Here’s the catch with it: It’s pretty poisonous, causing significant kidney cell damage. Burke’s method deconstructed the amphotericin compound, then reassembled it after excising the bits that caused kidney cell damage. The compound still works in killing fungi, but preclinical testing shows that this new version is otherwise innocuous.
So, outside of the antifungals, what kind of pipeline is Third Rock after with Revolution Medicines?
“That’s the billion-dollar question,” Goldsmith said, adding unhelpfully: “We’re looking at all the known drugs from the natural products space.”
The company’s casting an ultra-wide net to look for deconstructable drug candidates. There are three portfolios the company’s building, however – drugs in the antifungal space, drugs in the antibacterial and antibiotic space, and drugs that are already (take the chemotherapy agent Taxol, for instance) in use that can be optimized with the Revolution platform.
The ideal candidates will fit best into this building block method. Goldsmith kept mum on how long that $45 million will float Revolution Medicines, and what specific indications are of the most interest. This isn’t going to be a licensing play for the company, however – the financing round will be used to optimize and industrialize the platform, and flesh out the pipeline so that all drug development will be done in-house.
