A $50 million up-front payment from new partner Celgene Corp. gives Abide Therapeutics Inc. time to “focus entirely on the science, without worrying for a while about raising extra capital,” and the company likely has enough runway to reach “substantial milestones that would validate what we’re trying to do,” CEO Alan Ezekowitz told BioWorld Today.

The arrangement – including payments of undisclosed amounts when those milestones are reached, along with a rest-of-the-world license option for Summit, N.J.-based Celgene, which is taking a small equity stake – centers on Abide’s technologies to selectively target serine hydrolases.

“There are 125 of them, and if you extend them to the serine proteases, which are like the clotting factors and complements, there are about 200,” Ezekowitz noted. But only three drugs have emerged from the class so far: the diabetes drug Januvia (sitagliptin, Merck & Co. Inc.), the Alzheimer’s disease therapy Aricept (donepezil, Pfizer Inc.) and the obesity drug Xenical (orlistat, Roche AG).

Serine hydrolases “play a pivotal role in regulating a number of physiological processes, [but] if you looked at them from a sequence perspective, or even a structural perspective, you can’t tell a lipase from an amidase from a peptidase from a protease, and the reason for that is that they are not very homologous to one another,” Ezekowitz said.

San Diego-based Abide has assembled a “diverse library of chemical matter that targets selectively the active site of these enzymes” so that the company can “rapidly decode the targets from these different classes,” he told BioWorld Today. Phenotypic screens in animals can be done, too.

“We can go into whole animals and create chemical knockouts, which are equivalent of genetic knockouts in a time-dependent way,” Ezekowitz said. “The chemical tools that we use become the starting points for campaigns to develop selective compounds and lead optimization programs, so we really short-circuit the whole discovery paradigm.”

Included in the five-year Celgene deal is Abide’s most advanced compound, AB101131, due to enter first human studies in 2015. Abide expects to generate another three or four candidates during the five-year term of the collaboration, which will explore therapies for pain and inflammation. A monoacylglycerol lipase inhibitor, AB101131 works in the endocannabinoid system.

Abide also has a deal with Whitehouse Station, N.J.-based Merck & Co. Inc. in metabolic diseases, particularly diabetes. Last year, the pharma giant gave an undisclosed up-front payment to be followed by milestone rewards worth as much as $430 million. (See BioWorld Today, May 3, 2013.)

The collaboration with Merck is “proceeding very well,” Ezekowitz said, and further deals “at this point in time would be a distraction for us. There are significant-enough opportunities in these two spaces, and we’ve got a plan we want to execute.” But, he said, “science takes you many different places,” and other opportunities would be evaluated as they come along.

Last year, Abide won a grant of an undisclosed amount from the Cure Alzheimer’s Fund to study an enzyme in the serine hydrolase family as a therapeutic target for Down syndrome and Alzheimer’s disease.

Others have shown interest in serine hydrolases. In 2005, 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 Research Institute, now affiliated with Abide. (See BioWorld Today, Feb. 3, 2005.)

Proteomic technology from Scripps is important to the Abide platform. 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. But it’s Abide’s compound libraries and therapeutic engine that allow the company to take the next step in serine hydrolase research, Ezekowitz said.