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Biogen Start-up Escoublac Finds Link Between Bones and Obesity
[May 30, 2008]

Biogen Start-up Escoublac Finds Link Between Bones and Obesity

(BioWorld Today Via Acquire Media NewsEdge) By Tiffany Turner

Staff Writer

A new company hopes to unlock a link between bones and the bulge, providing a new way to treat obesity and diabetes.

Escoublac Inc., a Cambridge, Mass.-based start-up, was founded by Gerard Karsenty, chairman of the department of genetics and development at Columbia University Medical Center, whose work on osteocalcin, a peptide secreted by osteoblasts, could open a window to a new realm of therapeutics for metabolic disorders.

Karsenty said he first discovered the connection between osteocalcin, a protein found in bone and dentin, and metabolism by accident. In performing experiments where researchers knocked out osteocalcin in mice, Karsenty noticed that the mice without osteocalcin were plumper than animals with the protein.

"We became convinced that bone was an endocrine-regulating organism because we noticed that when we generated a knockout of osteocalcin, the mice were fat," he said.

"Since osteocalcin is made only in osteoblasts, and since it contributes to general circulation, there were only two ways to look at these results. One way was to ignore them, and the other way was to try and explain them."

Since 1996, Karsenty has been studying the effects of osteocalcin on metabolization, hoping to determine whether "bone was an endocrine organ regulating energy metabolism," Karsenty told BioWorld Today. That work paid off when researchers were able to show, "through a very long series of experiments," that osteocalcin can enhance insulin expression, secretion and sensitivity in mice, he said.

And now that work is translating into a business venture as Escoublac, the first start-up from Cambridge, Mass.-based Biogen Idec Inc.'s incubator, prepares to take its research into human trials.

Karsenty, for one, sees tremendous possibility for osteocalcin in humans.

"The potential is that it may help increase insulin secretion and sensitivity and energy expenditure in humans," he said. "That is certainly our hope, and the hope of Biogen and patients."

Indeed, Biogen is banking big on Escoublac and the link between osteocalcin and metabology. Nils Bergenhem, chief scientific officer of Escoublac, said that Biogen is providing Escoublac with the resources the company needs, both in terms of money and in terms of facilities.

"Basically, we can step into a lab here, where you have the permits and everything is in place to start work," Bergenhem said.

Karsenty said that Biogen's partnership with the company marks a good compromise of business and science, which will enable Escoublac to secure a steady stream of funding without lobbying for capital.

"The business plan has been from the start that we don't need to raise money," he said. "There are no other sources of funding besides Biogen. They have put everything on the table that we need at this point."

In turn, the company is operating as a semi-virtual organization with three employees. "If you look at business development and CEO functions, we don't really need them at this point," Bergenhem said.

He added that the incubator model, and Escoublac's partnership with Biogen, are serving the new company well and should help prioritize future growth efforts.

"All we're looking at bringing in house is some core technology that we need on a regular basis. Most technologies we need, if in the pharmacology or pharmacokinetics area, we can outsource," Bergenhem said.

Biogen benefits from the incubator relationship as well. In return for its financing of Escoublac, Biogen has a seat on the company's board. Biogen also has the option to acquire Escoublac in the future.

And in the long run, Biogen could benefit from Escoublac's innovation.

"This is a means by which they can evaluate new technologies, new ideas and to branch out and test concepts that they might not be able to do otherwise," Bergenhem said. "If they were to wait until an in-license project at a later stage, they would have to compete with a number of other companies."

Biogen is working with Escoublac to determine the most promising development path for a potential product, and the companies already have a well-established metabolizer, insulin, as a potential product model, Karsenty said.

"It's a hormone, and it works very well," he said. "So that's probably the first approach, and that's what we are doing right now."

Bergenhem summarized the company's approach: "Basically we're looking at uncarboxylated human osteocalcin as a drug candidate. We're evaluating the effects of it and looking at what, if anything, we need to do to make this into a viable drug candidate," he said.

In terms of competitors, Bergenhem pointed to Byetta, a first-in-class incretin mimetic co-marketed by San Diego-based Amylin Pharmaceuticals Inc. and Indianapolis-based Eli Lilly and Co. "If you look at a molecule like Byetta, you see an increase in insulin production and a decrease in weight," he said, and "if you look at what has been published on osteocalcin, there could very well be a similar effect profile."

In addition, Bergenhem said, Bagsv?rd, Denmark-based Novo Nordisk A/S has a horse in the diabetes race with liraglutide, a once-daily human analogue of the naturally occurring hormone glucagon-like peptide-1. Liraglutide works by stimulating the release of insulin only when glucose levels become too high and by inhibiting appetite. In contrast to other antidiabetic treatments, liraglutide leads to weight loss instead of weight increase.

In the meantime, with a large financial lifeline and a product candidate with large market potential in its pipeline, it looks as if the only uncertainty surrounding Escoublac is the meaning of its name.

Bergenhem said the company is named for a place he has never visited but hopes to soon. Karsenty was able to shed a little light, but not much more, on the significance of the company's name.

"It's named for the village of Escoublac in France, a place I vacation," he said. Indeed, if Escoublac succeeds in marketing osteocalcin, Karsenty might be due a few more days off. n



Copyright ? 2008 Thomson BioWorld, All Rights Reserved.

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