By Jim Shrine

Genetics Institute Inc. (GI) added the capability for small-molecule screening to its DiscoverEase library, and brought on the first two customers for the new platform.

Rhone-Poulenc Rorer Inc., of Collegeville, Pa., and Sankyo Co. Ltd., of Tokyo, became the ninth and tenth participants in GI¿s DiscoverEase program. They are the first to sign deals related to discovery of small-molecule drug candidates, in addition to the potential protein therapeutics to which previous partners gained access.

GI¿s DiscoverEase protein development platform is a functional genomics initiative to isolate and express a library of novel human proteins. They include extracellularly secreted proteins and those that are membrane-associated, which serve as targets for small-molecule screening.

¿Our agreements to date have focused on the extracellularly secreted [proteins],¿ said Adelene Perkins, GI¿s vice president of emerging business and general manager of the DiscoverEase program. ¿We have now moved into the next phase of the DiscoverEase program, which is the screening against targets in the library in search of small-molecule drug candidates.

¿What¿s unique about our programs is that we believe we¿re the only ones who make the physical cDNAs and expressed proteins available, so they can be directly used in biological systems to understand their function,¿ she said. ¿The other genomics programs are focused on in silico¿ ¿ or virtual ¿ genes, with sequences stored in computer databases.

¿We send out the physical reagent for people to test directly,¿ she added. ¿We¿re the only program that provides large numbers of the physical gene and protein for direct testing in biologic systems.

¿It¿s a very important distinction,¿ Perkins continued, ¿because we believe evaluating the function of these genes is truly facilitated by that biological testing. Looking at the sequence can be helpful, but the only way to tell what a protein does is by testing it in a biological system.¿

GI, of Cambridge, Mass., is a unit of Wyeth-Ayerst Laboratories, both of which are subsidiaries of Madison, N.J.-based American Home Products Corp. Specific financial terms of GI¿s DiscoverEase programs haven¿t been disclosed. But the structure of deals on the new platform is different, Perkins said.

For protein therapeutics, GI has been selling plates of proteins and cDNAs. Then, it has the option to co-develop and co-promote resulting protein therapeutics. Partners take an exclusive license on a first-come, first-served basis for a particular cDNA and protein for development.

Partners in the small-molecule program pay an up-front access fee ¿ along with milestones and royalties later ¿ for non-exclusive licenses to screen for small molecules against particular targets. GI retains no development or promotion rights.

¿It is our expectation, now that we¿ve added the small-molecule program, customers will sign up for both packages,¿ Perkins said.

¿We are very committed to maintaining a leadership position in having the most cDNAs and proteins being made available, because we believe that is the most interesting set of molecules to be working on,¿ she said. ¿We continue to see that being able to evaluate the function of proteins by putting them in complex in vitro and in vivo systems directly provides immeasurable information.¿

Among the sources for GI¿s clones are AlphaGene, of Woburn, Mass., and Genset SA, of Paris. GI has a technology partnership with Affymetrix Inc., of Santa Clara, Calif.

The DiscoverEase program became operational late in 1996. Genentech Inc., of South San Francisco, and Chiron Corp. of Emeryville, Calif., were the first customers. Others are Scios, of Mountain View, Calif.; Bayer Corp., of Pittsburgh; Ontogeny Inc., of Cambridge, Mass.; Immunex Corp., of Seattle; Chugai Pharmaceutical Co. Ltd., of Tokyo; and Kirin Brewery Ltd., also of Tokyo. n