ADVANCE/Corvas presents data at American Heart Association meeting on new antithrombotic agent discovered from a hookworm; progress on oral thrombin inhibitor also reported.

(ADVANCE) ANAHEIM, Calif.--(BUSINESS WIRE)--Nov. 15, 1995--A new direct inhibitor of Factor Xa, a blood-clotting enzyme, has demonstrated significant anticoagulant properties in preclinical studies presented Wednesday by researchers from Corvas International Inc. (NNM:CVAS), San Diego, at the 68th Scientific Sessions of the American Heart Association.

Progress in the company's development of an oral thrombin inhibitor was also reported. The abstracts were published in the October issue of Circulation, a journal of the American Heart Association.

Corvas scientists made scientific presentations of new data pertaining to their discovery of a unique family of small protein antithrombotic agents from the blood-feeding hookworm Ancylostoma caninum -- a parasite that has evolved efficient anticoagulant mechanisms to ensure its survival. Called Nematode Anticoagulant Proteins (NAP), this class of specific and highly potent compounds prevents blood clot formation by blocking the two earliest-acting enzymes in the body's coagulation process -- Factor Xa and VIIa.

George P. Vlasuk, Ph.D., Corvas vice president of biological research, reported results of preclinical studies evaluating the anticoagulant properties of NAP-5, a direct Factor Xa inhibitor belonging to the NAP family (Abstract No. 3287). In various rat models of thrombosis, a recombinant form of NAP-5 (rNAP-5) demonstrated efficacy and potential safety advantages over the commonly used clinical anticoagulant enoxaparin, a low molecular weight heparin (LMWH).

In a model of arterial thrombosis, rNAP-5 proved to be almost 1000-fold more potent than LMWH following intravenous administration. Subcutaneous administration in the same model demonstrated similar efficacy advantages for rNAP-5 over LMWH, and was accompanied by less overall blood loss.

Further experiments in an arterio-venous (AV) shunt model of thrombosis, as well as a model of venous thrombosis, showed that rNAP-5 was significantly more effective than LMWH, with a reduced risk of bleeding.

In another presentation, William E. Rote, Ph.D., senior pharmacologist at Corvas, described research indicating that rNAP-5 was highly effective in preventing arterial obstructions (occlusions) in a porcine model of coronary artery thrombosis following intravenous administration as well as subcutaneous dosing -- a more convenient dosage form (Abstract No. 2322).

"In these studies, rNAP-5 produced a powerful anticoagulant effect following both intravenous and subcutaneous administration, with no adverse side effects. These results suggest that rNAP-5 is a potent antithrombotic agent with a potentially favorable safety profile," said Vlasuk.

Oral Thrombin Inhibitor Provides Prolonged Antithrombotic Effect

The oral efficacy of CVS-1123 as a direct thrombin inhibitor was evaluated in a canine model of coronary artery thrombosis and heart attack in a study conducted by researchers at the University of Michigan Medical School (Abstract No. 1442). The compound was administered orally in capsule form to conscious dogs over an eight-hour period, and the animals were monitored continuously for 24 hours.

Results showed that CVS-1123 provided significant protection against the formation of blood clots in 73 percent of treated canines; in contrast, all animals in the placebo group developed an occlusive thrombus. Evidence of this protection continued throughout the entire 24-hour experimental period, even though the last dose was given at eight hours.

This result suggests that CVS-1123 provides a prolonged antithrombotic effect, with no indication of increased bleeding or adverse side effects.

"This study of CVS-1123 confirms the oral efficacy of our direct thrombin inhibitors in a model of acute coronary thrombosis," said Vlasuk. "Corvas' goal is to develop safe, oral anticoagulants that can be administered as preventive therapy to patients at risk for thrombosis caused by unstable angina and atrial fibrillation, as well as post-surgical patients in danger of suffering from deep vein thrombosis and pulmonary embolism."

Thrombosis occurs when blood clot formation, a normal vascular repair mechanism, is activated excessively. Thrombus formation can be harmful if the blood clot becomes very large, or is formed as the result of a major vessel injury. Cardiovascular diseases associated with thrombosis affect more than three million Americans annually and account for approximately half of all U.S. deaths.

Corvas International Inc. is a biopharmaceutical company engaged in the design and development of a new generation of therapeutic agents for the prevention and treatment of major cardiovascular and inflammatory diseases.

Corvas is currently collaborating with Schering Corp. in the development of oral thrombin inhibitors for chronic cardiovascular disease, and with Pfizer Inc. in the development of neutrophil inhibitory factor (NIF) as a possible stroke therapy, and has product licensing agreements with Ortho Diagnostic Systems Inc. (a Johnson & Johnson company), and Centocor Inc.

Founded in 1987, Corvas began trading as a public company in January 1992.

(End of advance for release 2:30 p.m. PST, Nov. 15)

CONTACT: Corvas International Inc., San Diego

John E. Crawford, 619/455-9800

Angela L. Hartley, 619/455-9800

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