the conventional small-molecule pharmaceuticals and the much larger engineered proteins made by biotech companies. The Ensemble approach is supposed to combine the best feature of conventional small-molecule drugs—their ability to be made into oral pills—with some of the more precise targeting features of large-molecule biotech drugs, like antibodies or other genetically engineered proteins. In the past couple years, Ensemble has shown it can make this new class of drugs so they bind specifically and tightly with their targets, and can be efficiently scaled up, a traditional difficulty with macrocyclics, Taylor says.
Under the deal with Bristol-Myers Squibb, the goal will be to develop Ensemble’s brand of drugs against eight biological targets that have traditionally been inaccessible to conventional small-molecule drugs, Ensemble says. Some of these targets are reachable by biotech drugs, but are hard to treat using protein-based drugs, because they are lifelong chronic diseases, and most biotech drugs must be taken by injection.
Ensemble still has a lot to prove—it’s at least a year away from completing the necessary animal tests for its lead drug candidate before it can enter its first clinical trial. But the first candidate is a real biggie—an oral pill designed to block TNF, an inflammatory protein that’s a common culprit in rheumatoid arthritis. This is the same target hit by three blockbuster biotech drugs—Amgen’s etanercept (Enbrel), Abbott Laboratories adalimumab (Humira) and Johnson & Johnson’s infliximab (Remicade). None of those companies, or anybody else, has come up with an effective oral blocker of this target. Ensemble hopes to identify its lead candidate against this target later this year, finish up animal tests, and go to the clinic in another year, Taylor says.
That’s the sort of milestone that I can imagine might get the VCs to open up their checkbooks again. If not, the deal with Bristol is structured in a way that gives Ensemble the flexibility to do more deals with Big Pharma companies. “We’re going to continue to emphasize our business development activities,” Taylor says. “It gives us the room we need to continue to develop the technology.”
