By Kevin Davies
February 8, 2012 | While many major pharma companies have been cutting back their research into natural products, Warp Drive Bio, a new start-up out of Third Rock Ventures in Boston, is dedicated to mining the genome of micro-organisms for potent natural product compounds. And in a striking $125-million deal, Warp Drive has teamed with Sanofi to provide ample funding to get operations off the ground and potentially into orbit.
Fresh off a stint as CEO of Foundation Medicine (where he remains chairman of the board), Alexis Borisy is Warp Drive’s chief executive. But he says the company is the brainchild of Harvard chemical biologist Greg Verdine. “It’s from his genius,” says Borisy. “Greg’s been working with us inside Third Rock for about two years on incubating and developing the ideas that are now Warp Drive Bio.”
Borisy says that he and Verdine bounced a lot of ideas around in the early days, but he was able to devote more time to the concept after recruiting Mike Pellini as Foundation’s new CEO. “Then we went to town on making Warp Drive a reality,” he says. “It’s a blue sky idea based on deductive reasoning. It’s a very early–stage company, but it has tremendous potential to completely re-imagine natural product drug discovery and what these molecules can do to open up the undruggable realm.”
The traditional way of isolating natural products was really hard, says Borisy, involving lots of microbe fermentation. But it was worth it. “Let’s recognize that the majority of all drugs that the industry has ever created are natural products,” Borisy points out. “As recently as 2010, half of the small molecules that year were natural products s or derived from natural products. So even though [natural product] investment in pharma has decreased, they continue to be a very productive source of new drugs.”
One of the chief appeals of natural products is that “they can do things that our fancy xenobiotic chemistries can’t do. Do you remember the last of Lipinski’s [Rule-of-Five] rules? For natural products, none of the other rules apply! Nature is a better medicinal chemist than we are. Nature creates molecules that can drug incredibly complex molecules, much more complex than synthetic chemistries.”
Some skeptics might argue that natural products are played out, but Borisy firmly disagrees. “Saying natural product discovery is exhausted is like saying in 1904, all physics had been discovered. Take bacteria: most bacteria can’t be cultured. So pharma strain collections only have 10% [all strains]. We know that only a small proportion of bacteria make drugs under lab conditions, about 10%. So all that work was probably on less than 1% of all possible molecules—and that may be an massive overstatement.”
Reading, Writing and Arithmetic
Warp Drive’s goal, then, is to re-envision a way, using technology advances in genomics, systems and synthetic biology, to jump start natural product drug discovery.
“Our platform is the three ‘R’s,” says Borisy: “Reading, writing and arithmetic.” Among the company’s other co-founders are George Church, a champion of new genomics technologies, and Jim Wells, an expert in protein-protein interactions. Among the dozen or so founding staffers is Keith Robison, formerly with Infinity Pharmaceuticals and author of the ‘Omics! Omics!’ blog.
Borisy is a little more guarded in describing Warp Drive’s novel platform, but it goes something like this:
“A little metaphorically, we can pick up a handful of dirt and basically explore all the sequence in there and read for a specific genomic signature. When bacteria make these natural products, they make them in a genomic cluster on the order of 100 kilobases. If there’s a chemical signature that we think is interesting and we’re looking for family members, we can query the sequence space using bioinformatics, pull out putatively interacting molecules, then cheminformatially predict what that molecule will look like. So the whole messy process is reduced.”
That’s the reading phase. The writing phase involves using molecular biology or synthetic genomics to make the cluster code and place it into a systems biology-engineered strain to produce it in large quantities. The arithmetic phase is simply “making it all add up.”
“We’re creating this genomic search engine to be able to access all of nature’s microbial diversity. Having a genomic search engine is great, but you can waste a lot of time in front of Google! It’s not just about having the engine but the search terms... That’s our special sauce.”
Warp Drive signed a $125-million deal with Sanofi, which is notable for a couple of reasons beyond the size of the equity investment. The French pharma helped co-found Warp Drive with both equity and non-equity dollars. If Warp Drive reaches certain milestones, then it has the option to sell the company to Sanofi for north of $1 billion.
“This has gotten lots of people talking,” says Borisy. “It shows how pharma is becoming more innovative.” Borisy says that half the industry has largely jettisoned natural products, while others still actively pursue them. Interest in the area has grown since the deal was announced. “Maybe we’re reigniting passion in this area,” says Borisy.
Warp Drive isn’t ready to talk about specific drugs or diseases, but focusing on showing that the platform works robustly and can apply across the board. “Our aim is to find really innovative molecules that will get everyone excited and create a tremendous product.”
In the meantime, Borisy remains “incredibly excited” about the prospects for Foundation Medicine, what he calls a “molecular information” company that aims to launch a clinical next-gen sequencing service for 200-300 frequently mutated cancer genes this summer.
“The founders felt this moral imperative to become broadly useful to people and fit into the real world of clinical oncology practice,” said Borisy. “The text exists, it is CLIA certified, and people who know about it can order it. Orders have been piling in via word of mouth—the demand has been extraordinary. What’s most gratifying is that in a majority of cases, we’re finding plausibly actionable aberrations.”