Ensemble Quietly Amasses Cancer Drug Pipeline, Scouts for New Deals

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picking its own targets and amassing a pipeline of potential drugs. The plan is to push them forward—possibly all the way into early human clinical testing—demonstrate some proof of their worth, and then form partnerships that are more lucrative than the drug discovery deals that got it started.

This strategy began with a deal on an oral inflammation drug inked with Novartis in 2013, when Ensemble was being run by Michael Taylor, now the CEO of another Boston-area biotech, Deciphera Pharmaceuticals. Ripple, a longtime biotech veteran who has led and sold other startups including Syntonix Pharmaceuticals (bought by Biogen) and Virdante Pharmaceuticals (acquired by Momenta Pharmaceuticals), aims to forge similar deals for a group of cancer drugs Ensemble’s now developing in-house. The goal is to get the company to the point that it would be a viable IPO candidate, an acquisition target, or maybe a merger candidate for a company that “has the development expertise” that Ensemble doesn’t.

“My job at this point in time is to make sure we’re building a business that would enable us to consider all of those strategic options,” Ripple says.

The company is targeting some pretty competitive and hot fields of research, like immuno-oncology and the ubiquitin-proteasome system, a garbage disposal system cells use to tag and trash unwanted proteins. The company has disclosed early stage programs targeting the enzymes IDO and TDO, which are thought to suppress the immune system’s response to cancer. It’s also going after a target called USP9x, one of many so-called deubiquitinating enzymes or “DUBs,” which are involved in a number of cellular processes.

Both of these efforts are early; Ensemble likely won’t begin its first clinical trial until “sometime next year,” Ripple says. And there’s plenty of competition out there on IDO drugs (Bristol-Myers, Pfizer, and Roche are among the players), which might be an important component of the combination regimens being advanced in cancer immunotherapy, and in DUB drug development (Forma Therapeutics, C4 Therapeutics and others) as well. Ensemble’s pitch is that it can apply the targeting power and precision of an antibody to a molecule small enough to get at targets inside cells. The purported benefit—which still has to be proven in clinical testing—would be drugs that could be delivered at higher doses and more safely, since they wouldn’t impact targets they’re not supposed to.

Conducting the clinical trials necessary to prove its technology’s worth will mean bigger bills for Ensemble going forward. No surprise that as Ripple says, the company’s first preference is to cut a deal to get a partner to help cover them. But if it can’t, it might finally be time, after all these years, to raise another round.

“These bets obviously increase in magnitude,” Ripple says.

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