Schering-Plough Corp. will help fund development andcommercialization of oral anti-thrombotic drugs being developed byCorvas International Inc. for the prevention and treatment ofcardiovascular disorders.

The alliance, announced Monday, provides for a $5 million equityinvestment in Corvas and another $5 million in research funding.The collaboration initially covers development of a thrombininhibitor. Schering-Plough has an option to expand the program tocover another blood-coagulation enzyme inhibitor, Factor Xa.

If both products are commercialized, Corvas, of San Diego, wouldrealize $80 million in various milestone, license and researchpayments. In addition, Schering-Plough, of Madison, N.J., will beresponsible for clinical development of all compounds from thecollaboration after completion of the Phase I trial of the leadthrombin inhibitor, CVS-1123, David Kabakoff, Corvas' presidentand CEO, told BioWorld. Corvas would get royalties for any productsales.

"This is an important milestone for us with respect to our oralprogram," Kabakoff said. "This announcement means we'vesatisfied one of our major strategic objectives for the year."

Schering-Plough (NYSE:SGP) purchased one million shares ofCorvas stock (NASDAQ:CVAS) at $5 per share, a premium of about100 percent to what Corvas has been trading at over the past fewmonths. Schering-Plough now owns about 9.7 percent of Corvas'10.3 million outstanding shares. Corvas was up 25 cents per shareMonday, closing at $2.88; Schering-Plough was up $1.13 at $74.25.

Kabakoff described the potential products as small compounds thatrecognize the business end, or active site, of an enzyme. Themolecules are designed to fit into the active site and inhibit thecatalyst from performing its function on the natural substrate. Theyalso are designed to inhibit specific enzymes.

Corvas recently initiated preclinical toxicology and pathology studieson CVS-1123. Pending satisfactory results, the compound isexpected to enter human trials in mid-1995, Kabakoff said. He said1123 was shown to be pharmacologically active in multiple animalmodels of thrombosis and can be given orally to multiple species,including non-human primates.

Corvas will take 1123 through Phase I trials. At that time Schering-Plough will evaluate the trial results and decide whether to fundfurther development. Schering-Plough also will fund all otherclinical trials coming out of the collaboration.

Kabakoff said there is an initial two-year research program in thethrombin area. Schering-Plough has a one-year exclusive option,renewable for a second year, on the Factor Xa program. If the FactorXa option is exercised, the terms would be similar to those in thethrombin deal, except that Corvas would get co-manufacturingrights.

Corvas uses computer-aided drug design technology and medicinalchemistry technology, as well as other approaches, in its discoveryprocess. Its Prism technology involves an approach to the synthesisof directed enzyme inhibitors using novel solid-phase synthesistechnology.

Some of Corvas' earlier work focused on monoclonal antibodies,particularly as anti-thrombotics. The company, which licensed itslead drug from that program to Centocor Inc., of Malvern Pa., in1991, decided that monoclonal antibodies were not going to be itsfocus.

Another development area, outside the Schering-Plough agreement,relates to inhibitors of Factor VIIa, a third enzyme involved in theblood coagulation cascade. Corvas also is working in the area ofinflammation. n

-- Jim Shrine

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