Xenova Ltd. has granted Hoffmann-La Roche exclusiveworldwide rights to develop microbially derived smallmolecules as immunosuppressants for use in organ transplants,and to treat autoimmune diseases and allergies.

Xenova, a drug discovery company based in Slough, England,granted the rights to F. Hoffmann-La Roche Ltd. of Switzerlandand its U.S. subsidiary, Hoffmann-La Roche Inc. of Nutley, N.J.The agreement "will ensure the rapid evaluation anddevelopment of these leads," said Louis Nisbet, chief executiveofficer of privately held Xenova, which retained rights to otherunspecified indications for the compounds.

The compounds were discovered through a joint discoveryprogram that began in 1988 and was largely carried out inXenova's laboratories. The research phase of the collaborationhas ended, and Hoffmann-La Roche will make payments toXenova, including royalties, said Nisbet.

The small molecules act as an immunosuppressant byinhibiting the binding of CD4 cell surface receptors to majorhistocompatibility complex class II proteins. This prevents theMHC proteins from binding to and bringing antigens into adocking position with the T cell receptor. Otherwise, a fragmentof CD4 activates the T cell receptor, which causes the T cells toproduce a series of molecules, including cytokines, that activatemacrophages and other cells that can cause damaging effects,such as organ transplant rejection.

"Roche contributed the CD4 receptor, and we used it to developthe screen for these microbially derived inhibitors of CD4,"Nisbet told BioWorld. "These compounds are the first smallmolecules known to inhibit this complex protein-proteininteraction. Interference at this site of action probably givesone the opportunity to interfere with T cell activation at theearliest stage in the process."

-- Kris Herbst BioWorld Washington Bureau

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