Critical limb ischemia is a condition characterized by significant impairment of blood flow to the legs and feet caused by a blockage of the arteries. It is the most advanced form of peripheral arterial disease. Increased risk for peripheral arterial disease is associated with lifestyle factors such as diabetes, high blood pressure, obesity, physical inactivity and high blood cholesterol, factors which are present in a significant and growing portion of the U.S. population . Patients with severe cases of critical limb ischemia may experience persistent pain in their lower extremities and may also suffer from severe tissue damage in the affected area. There are no drugs currently approved by the FDA for the treatment of this condition. The predominant treatment options for patients with critical limb ischemia are surgical procedures to restore blood flow, or revascularization, such as implanting a new blood vessel to bypass the blockage, or endovascular approaches, such as angioplasty, in which the vessel is unblocked from the inside using a balloon catheter or by installing a stent inside the vessel to maintain its opening.

The American College of Cardiology and the American Heart Association estimate that 50% of patients with a diagnosis of critical limb ischemia will either die or require amputation of the affected limb within one year of diagnosis. Similarly, the Sage Group, an independent research and consulting firm specializing in vascular diseases in the lower limbs, estimates that within six months of diagnosis up to 35% of critical limb ischemia patients will require limb amputation and 20% will die within this period.

In a study we commissioned, Trinity Partners estimated that approximately 1.0 million people in the United States have critical limb ischemia. In a study published in the journal Cardiovascular and Hematological Disorders, researchers estimated that approximately 10% to 40% of critical limb ischemia patients are not considered candidates for surgical revascularization or endovascular procedures. Trinity Partners estimated that approximately 30% of patients with critical limb ischemia have no revascularization options. According to the Healthcare Cost and Utilization Project, a family of databases sponsored by the Agency for Healthcare Research and Quality of the U.S. Department of Health and Human Services, the median hospital cost associated with a leg amputation was approximately $38,000 in 2005. Based on an assumed patient population of 100,000, we estimate the annual market potential for ALD-301 in the United States is $3.0 billion.