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Apofore Introducing New Diabetes Target ApoA-IV

By Jennifer Boggs
Managing Editor

The diabetes arsenal is chock full of marketed therapies – glucagon-like peptide-1 agonists, dipeptidyl peptidase-4 inhibitors and the so-called "glitazones" to name a few (though the latter has suffered from safety concerns over the past few years) – but the space has seen a shortage of promising new targets.

Enter Apofore Corp., a Cambridge, Mass.-based start-up founded last year to advance discoveries that naturally occurring protein, Apolipoprotein A-IV (apoA-IV), boasts the ability to reduce blood sugar and increase insulin production.

The protein apoA-IV previously had been identified as playing a role in inflammatory processes and food intake regulation, but its role in insulin secretion wasn't clear until the creation of apoA-IV knockout mice demonstrated reduced insulin secretion and impaired glucose tolerance. "That prompted us to do research about three, three and a half years ago," said Patrick Tso, professor in the department of pathology and laboratory medicine at the University of Cincinnati and Apofore's scientific founder.

Research by Tso and his team culminated in findings published in May in the Proceedings of the National Academy of Sciences showing that knockout animals on a high-fat diet, which usually become glucose intolerant, were able to secrete insulin with the help of apoA-IV.

And when evaluated in a mouse model of diabetes, animals with very high blood glucose receiving "a single injection of apoA-IV, at a modest dose, had normalized glucose for hours," Tso told BioWorld Today.

"The beauty of apoA-IV is its long half-life," he added. "It's in the circulation literally for hours, seven to eight hours."

Unlike GLP-1 and DPP-4, apoA-IV is found in a later phase of insulin secretion. Another advantage is that the protein only works when blood glucose is high; it's ineffective when blood glucose is low, meaning it won't cause hypoglycemia, a common side effect of drugs designed to control insulin levels, Tso said.

Apofore licensed rights to the technology from the University of Cincinnati to develop a recombinant form of apoA-IV for Type II diabetes. The firm was seeded with a $10 million investment from Cambridge, Mass.-based HealthCare Ventures LLC.

"We think it's got great potential and will add to the armamentarium [in diabetes]," said Jeff Packman, of HealthCare Ventures.

Apofore, which is operating in a virtual model with only a handful of employees, including Packman and Chris Mirabelli, managing director at HealthCare Ventures who is serving as the firm's president, currently is working on preclinical pharmacology studies to support the findings published in PNAS. It's also working on investigational new drug application-enabling toxicology studies, Packman said.

"We hope to move into the clinic in Phase I by this time next year," he told BioWorld Today.

There is still more work to do to understand the product's half-life and glucose-lowering effects. But Packman said the goal is to ideally develop drugs similarly dosed to diabetes drugs on the market. Recent approvals in the diabetes space offer patients once-daily and even once-weekly dosing.

ApoA-IV may also have applications in other areas, given its role in lipid metabolism, food intake and inflammation.

Apofore likely will look to hand the asset off to big pharma after clinical proof of concept. HealthCare Ventures' goal is to invest in preclinical and early stage companies, operating them as semi-virtual organizations and then seek returns through acquisitions.

"Our approach is to keep [Apofore] a very focused company," Packman said.