Telios Pharmaceuticals Inc. of San Diego and Genentech Inc. ofSouth San Francisco, Calif., announced Tuesday a $15 millioncollaboration to develop an improved anti-coagulant.

It could be a complement to Genentech's Activase tissueplasminogen activator (t-PA), which is approved for dissolvingblood clots following a heart attack.

The collaboration aims to develop short peptides to block theaggregation of platelets, which can form secondary blood clotsafter t-PA unclogs arteries. Aspirin and heparin are nowroutinely administered as a post-t-PA treatment of such clots.

The deal provides for Genentech to make milestone paymentsto Telios, which would also receive royalties on subsequentproduct sales. Genentech receives worldwide marketing rights,except in Japan and the Far East. Other financial terms were notdisclosed.

The pact draws on Telios' expertise with the RGD-based peptidethat mediates cell interactions. RGD peptides have been shownto block the IIb/IIIa platelet receptors, which can causeplatelets to clump. In preliminary animal studies with t-PA,RGD peptides have shown promising results in keeping arteriesclear of clots, said Telios spokeswoman Audrey Dickason.

A drug to inhibit platelet activation would complementGenentech's existing research on Argatroban, an amino acid-based compound that blocks the action of thrombin in bloodclotting. Genentech is conducting Phase I clinical trials ofArgatroban, but has not yet reported results.

The two drugs "would be used together, like aspirin andheparin are now," said Genentech spokesman Jack Murphy.

The new drug could be in clinical trials by the end of this yearfor use after t-PA administration, Murphy said. Genentech andTelios also plan to test it in preventing re-occlusion afterballoon angioplasty, in unstable angina, peripheral arterialocclusion and stroke.

Two other companies testing drugs to block plateletaggregation are Biogen Inc. of Cambridge, Mass., and CentocorInc. of Malvern, Pa. Biogen is testing in animals Applaggin, agenetically engineered form of a snake venom anti-coagulant.Centocor's Centorex, an antibody fragment that binds to theplatelet IIb/IIIa receptor, is in Phase II trials.

"It's too early to draw conclusions" on which approach willwork best, said Jacqueline Siegel, an analyst with Hambrecht &Quist in San Francisco. She said the optimal anti-coagulantwould have a high specificity for platelets, bind tightly but notirreversibly to them, and not cause an immune reaction inpatients. The market for anti-coagulants is estimated at morethan $150 million annually.

-- Carol Ezzell Washington Bureau Chief

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