By Mary Welch

Privately held Esperion Therapeutics Inc. raised more than $22 million in a Series C round of financing that will be used to advance its four cardiovascular therapies in clinical trials.

"We started with $20 million and went slightly north," said Tim Mayleben, Esperion's vice president and chief financial officer. "We turned away a couple of investors because we had a very, very strong response to our story. We were quite selective about our investors."

Existing investors who participated in this round included TL Ventures, of Wayne, Pa.; Oak Investment Partners, of Westport, Conn.; and HealthCap KB, of Stockholm, Sweden. New investors included Canaan Partners, of Rowayton, Conn., and Avalon Investments, of San Diego. TL Ventures and Canaan Partners co-led the financing. The company released details of the financing at the Chase H&Q Healthcare Conference in San Francisco.

Esperion, of Ann Arbor, Mich., has raised a little more than $40 million since its founding in July 1998, Mayleben said.

Esperion's goal is to exploit the high-density lipoprotein (HDL) pathway to remove excessive, disease-causing lipids, a process called reverse cholesterol transport. Lipoproteins are blood-borne particles that transport lipids throughout the body and contain a blend of cholesterol, proteins, triglycerides and phospholipids.

High levels of HDL reduce the risk of heart disease by countering the body's level of low-density lipoprotein (LDL) and the very low-density lipoproteins.

Esperion wants to reverse vascular disease by removing lipids from potentially unstable plaques in blood vessels called atherosclerotic lesions. Its initial area of focus is apoA-I Milano, a component of HDL. The apoA-I Milano, a variant of normal apolipoprotein A-L, was discovered by researchers who studied the local Milan, Italy, population, which, despite other risk factors, has a low incidence of cardiovascular disease.

"We believe we have a portfolio of product candidates to develop. We're not looking at one as the lead candidate in the traditional sense," Mayleben said. "This gives us a lot of options."

Esperion's one product that completed Phase II trials and is about to enter Phase II is pro-Apo-A-I, a natural biologically active human recombinant protein that has been shown to promote reverse lipid transport in humans. The company is developing it for the treatment of atherosclerosis.

Three other products are expected to start Phase I trials this year. ESP 24228 is a novel lipid formulation that enhances the body's capacity to mobilize cholesterol to the liver for elimination. It will start clinical trials for acute coronary syndromes.

The company in-licensed three new series of small amphipathic peptides that interact with phospholipids to form new HDL-like particles. These particles are effective in removing excess cellular cholesterol. The peptides activate the enzyme responsible for cholesterol esterification in the blood, a key factor in the reverse lipid transport pathway. The lead peptide, ESP 24218, is a very stable molecule in human plasma and dramatically increased the HDL cholesterol levels in rabbits. It will be tested as a treatment for atherosclerosis as well as ischemia.

Its third product that will enter Phase I this year is apoA-I Milano, a natural biologically active human recombinant protein that has opened arteries clogged by atherosclerotic plaque in animals. It will be tested as a treatment for ischemia and restenosis.

"We are an HDL product company," Mayleben said. "All of our drug candidates are in the areas of either delivering synthetic HDL or increasing the ability of HDL to remove cholesterol from the body. We will also be developing small molecules to increase HDL level's in people's bodies. We believe this area will be a huge market."