Tularik Inc. on Friday signed its fifth major corporate collaborationand fourth with a Japanese pharmaceutical company.

Tularik, of South San Francisco, and Japan Tobacco Inc., of Tokyo,agreed to work together to discover, research and develop drugs thatact through the regulation of leptin gene expression. Leptin is thehormone produced by the obesity (or ob) gene and a target of manyresearchers seeking to discover applications in such areas as obesityand Type II diabetes.

Privately held Tularik said its scientists discovered regulatoryelements that control transcription of the leptin gene and establishedhigh-throughput screens to identify drugs. The company has filedthree patent applications in the area.

Andrew Perlman, Tularik's vice president of medical research, saidthe leptin program is at an earlier stage than some others at Tularik."Nonetheless," he said, "we have made tremendous progress insetting up our first assays. The patent filings indicate we have madeprogress in understanding the elements responsible for regulation ofthis gene."

As in deals with its three other Japanese partners, Tularik retainedNorth American rights and, like two of those collaborations, keptrights in Europe as well. Only in a collaboration with Merck & Co.,of Whitehouse Station, N.J., in the area of viral diseases did Tularikgrant worldwide rights to its partner.

"It's a very appealing strategy for us," Perlman said. In general theJapanese companies are willing to lend their expertise and financialsupport without seeking rights outside Japan and other parts of Asia,he said. "Later we can either mount our own clinical programs or, ifappropriate, make other partnerships for the rest of the world."

The companies did not disclose specific terms of the collaboration.Japan Tobacco got exclusive rights in Japan and certain other Asiancountries. In return it is providing research support, milestonepayments and sales royalties to Tularik, Perlman said.

Tularik has collaborations with the Japanese companies TaishoPharmaceutical Co. Ltd., of Tokyo, in the area of immune systemdisorders, and with Sumitomo Pharmaceuticals Co. Ltd., of Osaka, inhypercholesterolemia. In both Tularik retained U.S. and Europeanrights. In a collaboration in inflammatory disease with YamanouchiPharmaceutical Co. Ltd., of Tokyo, the Japanese partner also gainedrights in Europe.

"Our area of expertise," Perlman said, "is broadly defined asunderstanding how genes are regulated," then developing assays todiscover drugs that will regulate the genes. Understanding what turnsa gene on or off gives the company specific targets for therapeutics.

Perlman said Tularik's goal is to have 80 percent of the company'sburn rate covered by funding from corporate partners. The companyhas raised $38 million in equity capital since its December 1991founding. Of that total about $32 million came from institutionalinvestors. Tularik has no products in human testing.

Tularik, in researching leptin, is involved in a field that has becomequite crowded and competitive since discovery of the ob gene in1994 by researchers at Rockefeller University in New York. AmgenInc., of Thousand Oaks, Calif., licensed rights to the discovery inMarch 1995. Amgen is testing its recombinant leptin in Phase I trials.

Among the companies with major efforts in the leptin area areMillennium Pharmaceuticals Inc., of Cambridge, Mass., and itspartner Hoffmann-La Roche AG, of Basel, Switzerland; LigandPharmaceuticals Inc., of San Diego; and Eli Lilly & Co., ofIndianapolis. (See BioWorld Today, Aug. 16, 1996, p. 1, and June 6,1996, p. 1, for more on recent work in the area.) n

-- Jim Shrine

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