turned any of its engineered macrocycles into an actual drug that has been approved by regulators, the concept intrigues pharmaceutical companies because of the potential to combine the precision targeting capability of a biologic drug with the advantages of a small molecule, which can be made into a convenient, oral pill. Ensemble’s drugs are designed to reach biological targets inside cells—so-called protein-protein interactions—that other drugs can’t reach. The idea of such mid-sized drugs, or even macrocycles, isn’t unique to Ensemble, of course. Several other companies, like Cambridge-based Aileron Therapeutics and U.K.-based Bicycle Therapeutics have been built on different ways to make mid-sized drugs. Research Triangle Park, NC-based Tranzyme specifically eyed macrocycles as well, before struggling, changing direction, and ultimately merging with San Diego-based Ocera Therapeutics.
Ensemble, however, distinguishes itself due to the largest library of man-made macrocycles out there, using a fast, cheap, industrialized method based on technology licensed from David Liu’s lab at Harvard University to create them.
“We are unique in applying a broad macrocycle capability and platform—we’ve had more success than most in hitting these very tough to drug protein-protein interactions,” Taylor says. “Companies like Tranzyme could use more traditional combinatorial chemistry to make maybe tens of thousands at most, and we’ve crossed the 10 million member hurdle recently.”
Taylor also says that Ensemble has designed its molecules to be both “drug-like and synthetically accessible.” Those molecules, then, aren’t as complex as the ones made by nature, meaning once Ensemble identifies a compound, it can make a drug out of it quickly.
Ensemble has used this idea to make the leap from just discovering drugs for others to making them on its own. The company designed an oral drug that blocks the cytokine interleukin-17, which is implicated in a slew of inflammatory diseases, among them psoriasis and psoriatic arthritis. A number of companies such as Novartis, Eli Lilly, and Amgen, are developing injectable drugs that inhibit IL-17, but Taylor says that Ensemble has the only oral candidate to target it.
“[Blocking IL-17] been extremely effective for treatment of psoriasis,” he says. “It basically cures psoriasis for many patients.”
Ensemble doesn’t ultimately see itself taking the IL-17 drug into the clinic on its own, however. Taylor says the program has garnered a lot of interest from pharmaceutical companies that are active in autoimmune diseases, and Ensemble plans to find a partner for the program before it begins clinical trials.
As for the company as a whole, however, Taylor says that an acquisition represents the most likely exit for Ensemble’s investors.
“I think its more likely that one of our partners or another pharma will see value in the platform and its very productive capability to hit some difficult targets,” Taylor says. “We think if we take care of the science, build value in the platform, and within our partnerships and our own pipeline, then something good is going to happen before too long.”
