National Editor

On the "trail" of a new cancer therapy, Human Genome Sciences Inc. and the pharmaceutical arm of Tokyo-based Kirin Brewery Company Ltd. entered a licensing deal centered on a protein discovered by the U.S. company.

The agreement is focused on agonistic human monoclonal antibodies to tumor necrosis factor apoptosis-inducing ligand receptor-2, also known as TRAIL Receptor-2.

Under the terms, HGS and Kirin will together identify and optimize the best candidate for clinical development.

"We hope to be able to make a decision within the next year," Jerry Parrott, vice president of corporate communications for HGS, told BioWorld Today.

HGS will develop and commercialize any resulting drug in North America, Europe and the rest of the world, excluding those areas where Kirin will develop and commercialize: Japan and Asia/Australasia.

Kirin would pay milestones and royalties to HGS for any product developed and marketed in its territories, and HGS would pay Kirin royalties likewise. Further details were not disclosed.

Rockville, Md.-based HGS discovered the TRAIL Receptor-1 and TRAIL Receptor-2 proteins. The human monoclonal antibody for the latter, known as TRAIL-R2 mAb, recognizes the protein found on the surfaces of a number of solid tumor and hematopoietic cancer cells.

Binding the monoclonal antibody (which mimics the activity of native TRAIL and therefore is regarded as agonistic) to the receptor triggers cell death. But, unlike native TRAIL, the monoclonal antibody doesn't bind to decoy-receptor surface proteins DcR1 and DcR2, or to the soluble receptor osteoprotegrin - a binding that fails to bring about cell death. Thus, the idea is to attack cancer with a binder that "wastes" less, and is more potent.

HGS and Kirin each have developed human antibodies to the target - HGS with partner Cambridge Antibody Technology, of Melbourn, U.K., and Kirin with help from Princeton, N.J.-based Medarex Inc.'s Xenomouse. HGS and Kirin have filed for patents on their respective candidates.

"If you go into the [scientific] literature, you'll find quite a bit of material," Parrott said. "A lot of people have done research on the TRAIL receptors, because of the apoptosis effect."

More than two years ago, South San Francisco-based Genentech Inc. and Seattle-based Immunex (since merged with Thousand Oaks, Calif.-based Amgen Inc.) entered a deal focused on similar research. (See BioWorld Today, June 2, 1999.)

Yaron Werber, analyst with S.G. Cowen in New York, said the tetrameric TRAIL ligand being examined in that effort "had manufacturing problems, and since then I believed they have resolved them, but the problem is that [the ligand] has a shorter half-life" than the monoclonal antibodies being researched by HGS and Kirin.

Werber called HGS's prospects favorable in the long term.

"They have a good team and they know how to do clinical trials - they're holding their own," he told BioWorld Today. "But it's all Phase I, really. The stock is going to trade on milestones, and there are not a heck of a lot of near-term clinical milestones," even though 2003 will see "a series of [drug candidates] moving into Phase II."

HGS' stock (NASDAQ:HGSI) closed Tuesday at $10.82, up 31 cents.