Millennium Pharmaceuticals Inc announced the initiation of a Phase I clinical trial of MLN1021, an orally administered inhibitor of Factor Xa, a critical enzyme in the formation of blood clots. MLN1021 will be investigated for a variety of applications in patients with thrombotic disease, including preventing and treating deep vein thrombosis and its complications, such as pulmonary embolism, and preventing stroke related to chronic atrial fibrillation. The randomized, placebo-controlled, dose-escalation study will assess the safety and tolerability, maximum tolerated dose, and pharmacokinetics and pharmacodynamics of MLN1021. It will be conducted at a trial site in the United Kingdom and include up to 64 healthy volunteers.

Factor Xa is responsible for the conversion of prothrombin to thrombin, which plays an important role in two key processes of blood clot formation in the blood vessels. These include the activation of platelets and the conversion of fibrinogen to fibrin, which helps stabilize the clot. Many currently available anticoagulants, or blood thinners, have narrow therapeutic windows and most are administered only by injection.

MLN1021 is a novel, proprietary, small molecule that targets a macromolecular complex, known as the prothrombinase complex, which is assembled on the surface of activated platelets and plays a central role in thrombin production. Factor Xa is the catalytic component of this complex.

MLN1021 is the fourth Millennium compound to enter into human clinical trials this year, and we are excited about the continued progress of our cardiovascular discovery program, said Robert Tepper, M.D., president, research and development, at Millennium. Factor Xa is an important and well-validated target for the treatment of patients with thrombotic disease. The MLN1021 program demonstrates the capability of our research scientists to advance novel discoveries into the clinic, and continues to reinforce the Company's world-class expertise in understanding and developing innovative treatments for thrombotic disease.

A thrombus, or blood clot, may impede the blood flow in the arteries or the veins, and may cause serious complications such as heart attacks and strokes. In deep vein thrombosis, a blood clot forms in damaged blood vessels or in places where the blood flow stops or slows down, such as the legs. A major risk related to deep vein thrombosis is that the blood clot will break loose and travel through the bloodstream. If this occurs, the clot may lodge in one of the smaller blood vessels of the lung, which is called pulmonary embolism. Each year, more than 400,000 people in the United States diagnosed with new or recurrent deep vein thrombosis or pulmonary embolism are treated with anticoagulant therapy. Additionally, several million people at high risk for these conditions including patients undergoing surgery and those immobilized as a result of acute illness, trauma or cancer receive anticoagulant therapy prophylactically.

According to the American Heart Association, about 15 percent of strokes in the United States occur in people with atrial fibrillation, a common type of irregular heartbeat that affects an estimated two million Americans. When blood does not completely empty out of the upper chambers of the heart, or atria, because of the heart's irregular pumping, a clot can develop in the blood that pools in the atria. The clot may travel from the heart to the brain, causing a stroke.