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develop drugs specifically designed to hit one of cancer biology’s best known, and hardest targets—a family of genes called RAS, which are implicated in more than 30 percent of all cancers, and 95 percent of the ones affecting the pancreas. The problem with RAS, so far, is that no one’s been able to successfully drug it. “It’s often described as a billiard ball,” Rizzuto says, meaning that it’s very smooth, and doesn’t have any obvious places for a drug to hook onto. (Another East Coast biotech, Cambridge, MA-based Warp Drive Bio, is trying to solve this problem and drug RAS in a different way, as Alex Lash wrote recently.)
Stockwell, who earned his PhD in chemistry working under famous Broad Institute of MIT and Harvard founding member and scientist Stuart Schreiber, has been using computational drug discovery techniques to find a way to target RAS. In doing so, Rizzuto says, Stockwell found “shallow pockets” on the surface of RAS where one could “dock very small chemical fragments” which could be connected to one another via a chemical backbone. “He ended up stitching together a molecule that looks nothing like the typical molecules in a drug company’s library,” Rizzuto says.
The idea is that these drugs would directly bind to RAS, and thus have a good chance of impacting RAS-driven cancers. Kyras is putting together a pipeline of small molecule drugs using this approach to hit RAS in different ways, and has hired Merck medicinal chemistry veteran Joe Vacca as its chief scientific officer to lead the effort.
It’s going to be awhile until Versant really knows what it has here—Kyras doesn’t expect its first human clinical trial to begin until 2018. And Rizzuto acknowledges that a number of high-promise computational drug discovery methods haven’t lived up to their hype. But he says that Versant has stress-tested Stockwell’s work with a number of outside drug hunting experts who came away impressed, and that the company has done a number of preclinical tests suggesting that its molecules are indeed directly binding to RAS. “That’s really what sold us at the end of the day,” he says. “Purely computational approaches aren’t worth much to me, unless you can actually show in the lab that the compounds are active.”
Stockwell will serve as a consultant to the company while keeping his position at Columbia. Rizzuto says the company is looking for lab space, and though it’s tough—finding an affordable home has been a crippling problem for New York biotech startups—he expects to have something together within six months.