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| |  Immune System Enzyme 'TACE' Cloned, Found to be Key to Arthritis Pill SEATTLE, Feb. 19, 1997 --A paper describing the cloning and description of an immune system enzyme that is a target for developing new rheumatoid arthritis treatments was published today in the journal Nature. Tumor necrosis factor-alpha (TNF) converting enzyme (TACE) was cloned and identified by Immunex Corporation as a new metalloproteinase, an enzyme that uses a bound metal ion to carry out its function. "This research is critical for two reasons: it proves TACE is the specific enzyme that chops off the TNF molecule from an immune system cell, causing a chain of events that can lead to diseases such as rheumatoid arthritis," said Roy Black, Ph.D., principal scientist at Immunex and lead researcher on this project. "Second, with this research we can now develop an inhibitor that may eventually lead to therapies that can be taken in a pill form to treat arthritis or other inflammatory diseases." Nature reports the cloning of the TACE sequence, which will enable Immunex collaborators to produce large amounts of the enzyme, critical to screening for appropriate protease (enzyme) inhibitors. Immunex has exclusively licensed its TACE technology to Wyeth-Ayerst Research, a division of American Home Products Corporation, and is working with them to develop and test TACE inhibitors. Immunex researchers compared TACE-deficient mouse cells to normal mouse cells (that included the enzyme) to determine how effective TACE is in cleaving TNF from the surface of cells. The research showed that the enzyme-deficient cells released only 10 percent of the amount of TNF that the normal cells produced. "We found that TACE inhibitors specifically target TNF levels, without disturbing other immune system functions," said Dr. Black. "This validates our goal to develop a therapy for rheumatoid arthritis patients that is specific to their disease." About Tumor Necrosis Factor (TNF) TNF is a naturally occurring immune system protein. It plays a key role in the cascade of events which lead to rheumatoid arthritis. Although some TNF is needed by the body to fight infection, the molecule can cause problems, such as rheumatoid arthritis, when too much TNF is produced in the body. TNF can exist in a cell surface form, and a soluble (free-floating form). A TACE inhibitor could prevent the release of the free floating TNF. TNF exerts its damaging action by binding to cell-surface receptors, which are specialized structures that transmit various signals to immune system cells. When TNF binds to a cell-surface receptor, it triggers a signal to the cell that causes a cascade of events that can lead to rheumatoid arthritis. Another type of TNF receptor is free-floating, or soluble. The soluble receptor acts as a decoy and prevents TNF from binding to the cell-surface receptor, preventing this devastating cascade of events. TNF Research Program Immunex is working on various ways to inhibit TNF. Immunex scientists have developed a soluble TNF receptor, called ENBREL(TM). When injected into rheumatoid arthritis patients, ENBREL can "mop up" excess TNF by binding it. ENBREL is currently in Phase III human testing in rheumatoid arthritis. In earlier studies, ENBREL was found to be highly effective at reducing swollen and tender joints of rheumatoid arthritis patients. The drug was also found to be well tolerated. While ENBREL may be available to patients soon, developing a TACE pill will require many years of development and clinical testing once a development candidate is selected. Immunex is a biopharmaceutical company which develops immune system products for the treatment of cancer, inflammatory and infectious diseases. American Home Products Corporation owns a majority interest in Immunex. AHP is one of the world's largest research-based pharmaceutical and health care products companies and is a leading developer, manufacturer and marketer of prescription drugs and over-the-counter medications. It is also a leader in vaccines, biotechnology, agricultural products, animal health care and medical devices. NOTE: This news release contains forward-looking statements that involve risks and uncertainties, including risks associated with clinical development, regulatory approvals, product commercialization and other risks described from time to time in the SEC reports filed by Immunex, including the most recently filed Form 10-Q.
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