In its first financing since it was founded in February 2005, Aegerion Pharmaceuticals Inc. raised $22.5 million in an oversubscribed Series A round to fund Phase II development of its lead dyslipidemia drug, AEGR 733.

Boston-based Advent International led the round, which also included investments from Geneva-based Index Ventures, San Francisco-based Alta Partners and Boston-based MVM Life Science Partners.

"We actually had more people interested in our Series A round than we had space for," said Jerry Wisler, president and CEO, attributing that interest to the growing size of the cholesterol-lowering drug market.

About 18 million people in the U.S. are treated with statins to reduce low-density lipoprotein (LDL) cholesterol, and "up until about five years ago, the belief was that it was a satisfied market," Wisler said.

Statin monotherapy could reduce LDL to 100 ml/dl, which, at that time, was the goal for high-risk patients. But later studies showed that achieving greater reductions were better, and the National Cholesterol Education Program revised its guidelines in 2004, recommending a goal of 70 ml/dl for patients at risk for cardiovascular disease.

"So the market has shifted to a point where statin monotherapy won't achieve the goal for the majority of patients," Wisler told BioWorld Today. "Now we're looking at a combination market."

That's where Aegerion's AEGR 733, a microsomal triglyceride transfer protein (MTP) inhibitor, comes in to play. Early research suggested that combining low-doses of AEGR 733 with a statin could further reduce LDL cholesterol levels, and ongoing Phase II development is aimed at confirming those findings.

As an MTP inhibitor, AEGR 733 is designed to work by a dual mechanism of action. It affects production of both VLDL in the liver and chylomicrons in the intestine, which are responsible for transporting cholesterol and triglycerides.

In prior studies, the drug showed positive efficacy data but appeared to have dose-limiting side effects, which is why Aegerion's "approach is to bring the dose down to complement the statins," Wisler said, "much like you've seen with Vytorin."

Vytorin is a tablet comprising two cholesterol drugs: a statin from Whitehouse Station, N.J.-based Merck & Co. Inc. called Zocor (simvastatin) and a cholesterol absorption inhibitor (CAI) known as Zetia (ezetimibe) from Kenilworth, N.J.-based Schering Plough Corp.

AEGR 733 initially will be aimed at two subgroups within the treated 18 million high-LDL population. The first, which is estimated to be anywhere from 3 percent to 10 percent, is made up of those who are intolerant to statin, either due to abnormalities in liver function or to discontinuation because of muscle pain.

Those who are not able to take statins are left with less efficacious alternatives that might only reduce their LDL levels by 10 percent to 15 percent, instead of a 35 percent to 55 percent reduction.

But by combining AEGR 733 with one of the non-statin drugs, such as CAIs, "we could bring them back into that range," Wisler said.

The second subgroup is much bigger and includes patients who are on statin therapy but have not been able to achieve LDL levels of 70 ml/dl.

The company did not disclose how long the Series A funding would sustain operations, but Wisler said the money is expected to "fully fund" Phase II development of AEGR 733. Two trials are ongoing, with results expected by the end of the year, and two additional studies are set to start around September.

"We've had great support so far," Wisler said, "and if these trials show what we hope they're going to show, there should be a lot more interest."

The Bridgewater, N.J.-based company was founded by Wisler and David Scheer and the lead compound was licensed from the University of Pennsylvania. Aegerion has 10 employees, and Wisler said that number will increase as needed to keep up with clinical work.

In the meantime, the development-stage company is interested in expanding its pipeline. It's in discussions to potentially in-license additional compounds in cardiovascular and metabolic disease.

In connection with the financing, Jason Fisherman, of Advent; Kevin Johnson, of PanGenetics (representing Index); and Allison de Bord, of Alta, joined the company's board.

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