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Abide Therapeutics, Merck: Type II Diabetes Deal Worth up to $430M

By Randy Osborne
Staff Writer

Abide Therapeutics Inc.’s potential $430 million with Merck & Co. Inc. is focusing on Type II diabetes by way of small molecules that take aim at members of the serine hydrolase enzyme family.

San Diego-based Abide’s platform involves proteomic technology from The Scripps Research Institute. A probe labels the active sites of serine hydrolases, after which Abide scientists screen the Scripps-made, 1,000-member small-molecule library to find compounds that obstruct the probe’s labeling of a given enzyme.

Serine hydrolases represent one of the largest and most diverse enzyme classes, about 1 percent of all human proteins. Drugs that target specific serine hydrolase enzymes have already been developed for the likes of obesity, diabetes, microbial infections and Alzheimer’s disease. But inhibitors have yet to be made for the majority of the known serine hydrolases.

“They’re the last untapped enzyme class,” Alan Ezekowitz, Abide’s president and CEO, said of the serine hydrolase class. G-protein coupled receptors and kinases “have been very actively pursued as drug targets for good reasons. Unlike kinases, which are similar to one another, once you get a targeted [serine hydrolase] inhibitor, it’s very selective for that molecule. And when you use a gel-based proteome analysis, you get the whole proteome. You get all the possible combinations of the serine hydrolases in one gel, from one particular tissue, whether it be brain or muscle.”

Under terms of the deal, which involves three product candidates, Abide gets an upfront payment and research funding, plus possible milestone payments of up to $430 million. Further details were not disclosed. Whitehouse Station, N.J.-based Merck will have worldwide commercialization rights, and would pay royalties to Abide.

Serine hydrolases last made news in 2005, when ActivX Biosciences Inc., of La Jolla, Calif., was acquired by Tokyo-based Kyorin Pharmaceutical Co. Ltd. in a $21 million deal that set up ActivX as a U.S.-based research center to pursue work in the field. Among the founders of ActivX was Benjamin Cravatt, of Scripps, who now works closely with Abide. (See BioWorld Today, Feb. 3, 2005.)

“It’s divorced from what happened with ActivX, but because it’s Ben Cravatt, it’s a next generation, if you like,” Ezekowitz told BioWorld Today. “What’s really unique [about Abide’s approach] is not so much the probe technology, which is at ActivX, but the compound libraries and the therapeutic engine” that take the research a step beyond, he said.

“What we’ve been able to do is solve a conundrum that was a technical barrier to looking for other members of this family,” including those involved in mediating glucose regulation, Ezekowitz said. “Only three [in the class] have been drugged.” One is Merck’s DPP-4 inhibitor Januvia (sitagliptin), approved by the FDA in 2006 for Type II diabetes.

“When you are thinking about diabetes, they are always combination therapies,” Ezekowitz noted. “You start off with metformin, and then you build above that, at least in the oral glycemic control paradigms. The goal of the collaboration is to look in animal models, which are predictive in Type II diabetes for novel targets that might act in concert with DPP-4 inhibitors or act wholly independent of them.”

The Abide platform’s appeal for Merck apparently overcame regulatory hurdles in diabetes that may have discouraged others. “Given the fact that we can measure off target, that reduces the risk,” Ezekowitz said. “I think Merck is clearly in this field for the long haul, and understands that they are going to have to do a cardiac outcome study. If they didn’t think they would carry at least one of these three targets that we end up choosing to the endgame, then they wouldn’t [have begun] this collaboration.”

See Friday's BioWorld Today for More on This Story.