By Lisa Seachrist

Washington Editor

3-Dimensional Pharmaceuticals Inc. and Wyeth-Ayerst finalized an agreement worth $64 million should the companies successfully collaborate to develop and market a drug to inhibit thrombin -- an enzyme that converts fibrinogen into fibrin and causes blood clots.

Under terms of the agreement, Wyeth-Ayerst will gain worldwide rights to 3-Dimensional's orally active thrombin inhibitors currently in preclinical development as well to as any follow-on compounds in return for immediate cash, equity investment, and milestone payments totaling $64 million if an initial product for combating deep vein thrombosis, atrial fibrillation and clots resulting from heart valve replacement comes to market.

Should a second compound reach the market, the total payment will hit $112 million.

In addition, Wyeth-Ayerst, of St. Davids, Pa., will fund all research, development and licensing costs associated with the program. 3-Dimensional also will receive royalty payments for any products that make it to market. Wyeth-Ayerst is a division of American Home Products Corp., of Madison, N.J.

"3-Dimensional has advanced its thrombin program in a very efficient and cost-effective manner," said Thomas P. Stagnaro, president of the Exton, Pa., company. "We view the licensing agreement with Wyeth as an important validation of our technology platform."

Drug Found In Less Than Two Years

3-Dimensional uses a structure-based drug design protocol with its method of directing combinatorial chemistry toward specific molecular targets called DirectedDiversity. The method allows the company to use virtual drug design to rapidly discover and optimize new drugs.

Scott Horvitz, chief financial officer with 3-Dimensional, told BioWorld Today that using its technology, the company needed only 20 months to develop highly orally bioavailable drugs to inhibit thrombin.

Currently, 6.9 million Americans are treated each year for clotting conditions, which include heart attack, stroke, deep vein thrombosis associated with surgeries and sustained arrythmias. Warfarin, one of the most common drugs used to treat thrombotic conditions, requires that a physician closely monitor patients to prevent life-threatening hemorrhages. In addition, even though it is orally administered, it is very slow to act.

By way of contrast, 3-Dimensional's compounds have proven themselves to quickly enter the bloodstream in animal studies and directly act on thrombin. As such, they may offer a more precise and safer way to prevent blood clots from forming.

"This represents a huge unmet medical need," Horvitz said. The market for such a product has been estimated at anywhere between $500 million and $1 billion per year.

Horvitz also noted 3-Dimensional expects to take one of its thrombolytics into clinical trials sometime in 1998. Should 3-Dimensional meet its milestones in the first year, Horvitz told BioWorld Today that Wyeth would pay $10 million in up-front and research and development payments.

3-Dimensional also is working on anti-metastasis compounds designed to inhibit urokinase and is collaborating with BioCryst Pharmaceuticals Inc., of Birmingham, Ala., to develop inhibitors of the complement cascade. *