By Lisa Seachrist

Washington Editor

Atherosclerosis expert AtheroGenics Inc. raised $15.9 million in a private sale of Series C convertible preferred stock to continue clinical development of its cholesterol-lowering and vascular protectant compound, AGI 1067.

With the addition of these funds, the Alpharetta, Ga.-based company has a total capitalization of more than $30 million. Cordova Ventures, an Atlanta-based venture capital firm, led the financing, which included all previous investors in the company as well as several new investors.

¿It¿s always good to have the continued support of your investors,¿ said Russell Medford, president of privately held AtheroGenics. ¿With the strength of the science behind our technology, we are looking to develop a whole new class of agents that manage the process of atherosclerosis, not just the risks.¿

Atherosclerosis is a complicated disease process in which inflammatory reactions to blood vessel damage result in arteries narrowing with fatty plaque deposits. High cholesterol, high blood sugar, high blood pressure and smoking all increase the risk of blood vessel damage, which serves as a seed for the formation of those fat deposits.

To date, physicians have been limited to helping patients lower their risk factors for atherosclerosis by encouraging them to stop smoking and eat more healthily, and by providing medications to lower blood cholesterol and blood pressure. The mainstay of this strategy has been the statin, or HMG CoA-reductase, drugs. Those drugs function by altering liver metabolism to decrease the cholesterol level in the blood.

AtheroGenics scientific founders Russell Medford and Wayne Alexander look at the process in a different way. Based on their work at Emory University in Atlanta, the researchers decided to aim at the common inflammatory process through which all of the risk factors contribute to atherosclerosis.

When endothelial cells are activated by an injury to the blood vessel wall, a cascade of genes turn on and amplify inflammation by producing proteins that summon the cells of the immune system. AtheroGenics has produced a small-molecule, orally available drug, AGI 1067, to inhibit portions of that cascade. Specifically, AGI 1067 stymies the production of vascular cell adhesion molecule-1, or VCAM-1, which serves as a docking point for leukocytes and monocyte chemoattractant protein, MCP-1, which attracts leukocytes.

¿AGI 1067 is the first drug candidate that targets that pathway,¿ Medford said. ¿And we hope that it will be one of a new class of therapeutics for this disease.¿

Company Preparing For Phase II Program

In addition, AtheroGenics has designed the drug to lower cholesterol levels as well through mechanisms separate from the statin drugs. The company has completed a Phase I study of the drug as a cholesterol-lowering agent and is preparing to start on its Phase II program, which will include several studies.

¿We will be looking for an indication in cholesterol lowering,¿ Medford said. ¿Efforts to demonstrate [AGI 1067¿s] anti-atherosclerotic activity will come in the post-market environment.¿

Medford noted that AGI 1067 not only lowers cholesterol, but also augments the capacity of statin drugs to lower cholesterol.

¿There is a significant patient population that cannot reach their target cholesterol levels with statins alone,¿ Medford said. ¿This may offer them the opportunity to regulate their risk without resorting to high doses of statin drugs.¿

Medford said AtheroGenics has no partner now for AGI 1067, but that the company is looking for such a collaboration.

¿This is a technology platform that affords us other opportunities to treat diseases such as asthma, arthritis and inflammatory bowel disease,¿ Medford said.

In addition to the vascular protectant technology, the company is developing a diagnostic test that detects active atherosclerosis, which could be used by physicians to monitor how well current therapy is managing a patient¿s disease and perhaps identify patients who have active atherosclerosis despite showing no outward signs of disease.

The company also is developing products to impose growth control on cancer cells.