Zafgen is creating drugs to shrink fat. Today, the Cambridge, MA-based biotech company took an early step toward its goal by hiring its first permanent CEO, Tom Hughes, the former vice president and global head of cardiovascular and metabolism research at the Novartis Institutes for Biomedical Research in Cambridge.
Hughes, 49, says he was drawn to the company for three reasons: its method for treating obesity is unlike anything else in development, the disease is a monster public health problem, and the company has solid backing from Atlas Venture and Third Rock Ventures. The company’s intellectual property is based on research done by Maria Rupnick at Children’s Hospital in Boston. Rupnick has shown, in work published in the Proceedings of the National Academy of Science, that experimental drugs can interfere with the growth of new blood vessels in fat tissue. That causes mice to lose weight, and have their fat tissue shrink, while maintaining lean body mass. Many other drugs in development for obesity work on receptors in the brain, trying to coax the body to think it’s full and stop eating.
The market opportunity might be the biggest ever in the pharmaceutical industry. About two-thirds of American adults are overweight or obese, according to the Centers for Disease Control and Prevention. Medical expenses in the U.S. from obesity totaled $75 billion in 2003, half financed by taxpayers, according to the CDC.
Zafgen believes it can build on some of the lessons researchers have learned when fighting cancer to the growing obesity epidemic. Several drugs, like Genentech’s Avastin, have shown that cutting off the flow of blood to tumors can work against cancer. Zafgen’s idea is that fat tissue, like tumors, also has lots of blood vessels growing in it, and thrives on an ability to grow new ones as it expands—so interrupting that process can make a difference.
“This is not an idea that’s being discussed openly or broadly at scientific meetings, but this is a field that’s going to blow wide open,” Hughes says.
A lot still needs to happen first, but Hughes brings credibility to the task. He spent 20 years at Novartis, where he conceived and led critical animal experiments that paved the way for vildagliptin, a first-in-class diabetes drug that is approved in Europe. Hughes’ work at Novartis focused on blood-sugar balance, diabetes complications, and fat metabolism, among other things. He won Novartis’ distinguished scientist award in 2000 for the diabetes effort.
“Tom’s experience is ideally suited to lead Zafgen through our next stage of growth as we prepare to enter the clinic with our first drug candidate in 2009,” said Peter Barrett, a partner with Atlas Venture, in a statement. “His move to join Zafgen is further validation of this disruptive approach to treating obesity.”
Zafgen currently has only eight employees, and intends to stay small partly by relying on contract research organizations and academic collaborators, Hughes says. It has about $24 million in capital, and he plans to manage it carefully, he says. (No fat in his spending plan.)
As with the development of any drug, Zafgen’s effort will face plenty of obstacles. The safety profile of a drug that has potential to be taken by millions of people has to be squeaky clean in the post-Vioxx era. French drug giant Sanofi-Aventis (NYSE: SNY) suffered a major setback last year when an FDA panel rejected its drug Acomplia because of a possible risk of suicide. “Any new agent here is going to have to be very well-tolerated and safe and quite effective,” Hughes says. “The hurdles here are very high, we’re quite aware of it.”
One of the first things Zafgen will need to show is that its drugs, which interfere with grow of blood vessels in fat tissue, don’t get in the way of normal growth of blood vessels elsewhere in the body and cause side effects. For example, an athlete with a torn knee ligament, like New England Patriots’ quarterback Tom Brady, needs growth of new blood vessels to the injured area to promote healing.
Another big question I had: Why does the fat tissue shrink after growth of blood vessels is cut off, instead of just remaining dormant? “It’s new science,” Hughes says. “These are fascinating questions we’re going to work to answer in people.”
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