3-Dimensional Pharmaceuticals Inc., founded three years ago withcomputer-controlled drug discovery technology to speed selection oftherapeutic compounds from huge combinatorial chemistry libraries,signed its first major collaboration with Germany-based MerckKGaA for up to $10 million over two years.

Exton, Pa.-based 3-Dimensional will apply its technology, calledDirectedDiversity, to refine the potency of potential drug compoundsgenerated by Merck, of Darmstadt, Germany, against a specificgenetic target involved in cardiovascular disease.

Thomas Stagnaro, president and CEO of 3-Dimensional, said hiscompany will receive an up-front "multimillion dollar" equityinvestment by Merck and will receive the balance of the $10 millionin research funding and milestone payments. 3-Dimensional also willearn royalties on marketed products.

Based on the success of the current project, Merck may expandapplication of 3-Dimensional's technology to other genetic targets,generating additional income for his company, Stagnaro said.

Earlier this year Merck gained access to human gene sequence dataand related biological information through a collaboration withHuman Genome Sciences Inc., of Rockville, Md., and its primarypartner, SmithKline Beecham plc, of London.

3-Dimensional's DirectedDiversity technology combines computer-controlled rational drug design with combinatorial chemistry.

Based on the configuration of the genetic target, 3-Dimensionalcreates virtual compound libraries, which are screened by thecomputer to identify the best fits and sorted into sublibraries. Thosecompounds are then synthesized and screened for activity inbioassays. Data from the assays are analyzed and stored by thecomputer for use in creating a more refined sublibrary of compoundsfor the next round of tests.

A key element of the DirectedDiversity approach, company officialshave said, is that after the best virtual drug candidates arebiologically evaluated in the laboratory, detailed information abouttheir structural activity relationships with the genetic target areretained and fed back into the computer for the next iterativegeneration of compounds for assessment. Normally informationabout activity against a target is lost if the compounds are not hits.

Stagnaro said his company expects to negotiate "one or two" morecollaborations similar to the Merck deal with other pharmaceuticalfirms.

He added 3-Dimensional is talking with biotechnology companiesabout joint drug development programs in which revenues from thealliance would be shared equally.

In addition, the company is engaged in its own drug discovery,generating compounds for development partnerships with other firms.The most advanced program is aimed at thrombin inhibitors. WithDirectedDiversity, 3-Dimensional was able to identify in 16 months asmall- molecule compound with sufficient potency to enterpreclinical trials as a thrombin inhibitor. n

-- Charles Craig

(c) 1997 American Health Consultants. All rights reserved.

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