NEWS CELSUS RECEIVES NIH FUNDING FOR DEVELOPMENT OF NEW ANTICOAGULANT2/23/01 -- Celsus Laboratories, Inc. announces its receipt of a research grant from the National Heart, Lung, and Blood Institute to fund a collaboration with Loyola University Medical Center (Maywood IL) to continue the development of Intimatan as an anticoagulant for use in interventional cardiology. Intimatan is a patented complex carbohydrate comprising a rare disaccharide sequence of repeating L-iduronic acid -> N-acetyl-D-galactosamine 4,6-O-disulfate joined by 1,3 and 1,4 linkages. Current practice for cardiopulmonary bypass (CPB) surgery requires high dose heparin (400 U/kg) to maintain patency of the extracorporeal circuits during flow. However, thrombin bound to the fibrin clot, vessel wall and biomaterial surfaces are typically resistant to inhibition by heparin. In comparison with heparin, using a pig model of CPB, Intimatan maintained extracorporeal patency at one tenth the anticoagulant dose; generated a 4-fold lower activated clotting time (ACT); reduced chest wall bleeding more than 2-fold; and did not induce thrombin rebound or require neutralization post-procedure. The need for post surgical neutralization of heparin often results in heparin- protamine-complex-induced complement activation which contributes to postoperative edema. The administration of heparin also contributes to the incidence of heparin-induced, type II thrombocytopenia (HIT) and its associated thrombosis also known as "white clot syndrome". Patients with HIT are at high risk for thrombo-embolic complications. HIT is caused by heparin-related and platelet activating antibodies which may be present up to 100 days after the cessation of heparin therapy. Alternative anticoagulants are needed in HIT-patients. Early studies show that Intimatan has minimal cross-reactivity with HIT antibodies and a reduced hemorrhagic profile. "We believe we have a truly remarkable molecule here and are confident that a collaboration with the Cardiovascular Institute and Thrombosis Research Laboratories of Loyola University will further stage the development of Intimatan for clinical use based on a different mechanism of action and a better therapeutic profile than heparin" remarked Cornelius L. "Case" Van Gorp, founder and president of Celsus Laboratories. Dr. Alan D. Cardin, Celsus' vice president and the principal investigator of this grant, explained Intimatan's mechanism of action as follows: "In contrast to heparin, Intimatan is an agonist that targets the binding of heparin cofactor II to exosite 1 of thrombin, the same exosite targeted by hirudin, the leech anticoagulant. Moreover, Intimatan mediates the sustained inhibition of thrombin on the vessel wall. As thrombin rebound is an important issue clinically, Intimatan may fulfill a unique unmet medical need in the management of acute coronary syndromes and post operative treatment of deep vein thrombosis". Celsus Laboratories, Inc., a closely-held enterprise founded in 1987, manufactures various sulfated glycosaminoglycans in the form of dermatan sulfate, heparan sulfate, heparin derivatives and the low molecular weight heparin ardeparin sodium, as well as Intimatan. Celsus offers its products throughout the world and on line at www.heparin.com.
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