The pharmaceutical business tends to split into a couple of camps: Either molecules ought to be small, or large. But some interesting work these days is happening in the middle, where Cambridge, MA-based Ensemble Therapeutics has been carving out its niche.
Ensemble has been toiling away since 2004, based on work in David Liu’s lab at Harvard University, to synthesize a class of mid-sized molecules known as macrocycles. The idea is to try to combine the best of both worlds with small and large molecules. The mid-sized drugs are supposed to have a big advantage of traditional small-molecule drugs-their ability to be made into oral pills-along with the precision targeting capability of large-molecule biotech drugs, like antibodies or other engineered proteins. Ideally, the mid-sized drug candidates should be lean and mean enough to hit biological targets inside cells that bulkier protein drugs can’t reach.
There have been plenty of skeptics. Macrocycles are complex molecules found in nature. Scientists know they can sometimes be made into useful pharmaceuticals, including antibiotics like erythromycin, but no one has developed a fast, cheap, industrialized way to synthesize new macrocycle drugs to fill up a library, like with small molecules. It’s only been in the last year, Ensemble CEO Mike Taylor says, that the company has really hit its groove, developing a method that had created a vast library of about 3 million new macrocycles (soon to be an estimated 4.2 million) with potential to run through screening campaigns against some of biology’s hard-to-reach targets.
All of Ensemble’s molecules are still in their infancy, and need to run the usual gauntlet of tests in animal models before the company even thinks seriously about advancing them into clinical trials. But Ensemble has gotten much positive feedback from its two partners, Pfizer and Bristol-Myers Squibb, and is now in position to add a third or, maybe, fourth partner, Taylor says.
“There were a lot of biases against macrocycles when we started, based on historic challenges,” Taylor says. “We had a checklist to work on, to convince people that yes, we could make lots of them, and yes, we can make discrete molecules, and yes, we can make them with drug-like properties, and yes, we can get them into cells. There were about 12 things we had to tick off, which we have essentially done.”
Ensemble recently reported that it had been granted a couple of key patents on its technology. This patented method has put little Ensemble, with a little more than 30 employees, in a position to do what Big Pharma companies do—run industrialized campaigns to see
