Ensemble Therapeutics can add Alexion Pharmaceuticals to the list of believers in its drug discovery engine.
Cheshire, CT-based Alexion (NASDAQ: ALXN), the company that has made a fortune off of the super-expensive rare disease drug eculizumab (Soliris), has become the latest company to tap into Cambridge, MA-based Ensemble’s library of synthetic macrocycles—molecules intended to combine the properties of both small-molecule drugs and biologics, like antibodies, to blast tough-to-reach biological targets.
The two companies didn’t disclose the financial numbers surrounding the partnership—CEO Mike Taylor would only say the figures are “quite financially attractive”—but under the deal, Alexion will identify various drug targets it wants to attack, and Ensemble will screen its library of more than 10 million macrocycles to find ones with the best chance to hit those targets in a meaningful way to become drugs.
Ensemble will get an unspecified upfront payment as well as research support, and stands to tack on various milestone payments tied to development and commercialization goals. Alexion will get the rights to develop and commercialize any drugs that come out of the partnership.
The partnership marks the latest strategic move for Ensemble, which has quietly assembled a sizeable cast of collaborators. Since 2009, Ensemble has struck drug discovery deals with Bristol-Myers Squibb, Pfizer, Roche’s Genentech unit, and Boehringer Ingelheim. Its success in doing so has kept it from needing a significant infusion of venture capital since 2007. Ensemble has raised around $38.5 million in equity financing to date from Flagship Ventures, Arch Venture Partners, CMEA, Harris & Harris, Kisco Ltd., and Boston University. The company has enough cash to operate for several more years because of the collaboration dollars, Taylor says.
Besides the extra financial runway the Alexion partnership gives Ensemble, it also allows Ensemble to expand its platform into the rare disease space, which hasn’t been the focus of its previous collaborations, Taylor says.
“This is a very important deal for us,” he says. “[It’s] going to allow us to develop the platform into these new areas, as well as to help provide funding for the Alexion work and some funding for our internal efforts as well,”
Ensemble has been able to successfully attract partners because of both the sheer size of its library of synthetic macrocycles, and the efficiency with which it can screen that library for drug candidates against certain biological targets. Though Ensemble hasn’t 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.”