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Rigel Uncovers Function of a Key Protein Involved in Production of Antibodies That Can Cause Allergies and Autoimmune Diseases

Study Published in Proceedings of the National Academy of Science

South San Francisco, California - March 08, 2000

Rigel Pharmaceuticals, Inc. today announced that a team of scientists, including several Company advisors, used Rigel's retroviral expression technology to further define the biologic function of SWAP-70, a protein that regulates the production of human antibodies that can trigger the onset of allergies and autoimmune diseases. The study is published in a recent issue of the Proceedings of the National Academy of Science.

SWAP-70 was first identified in 1998 by the same group of scientists who reported that the protein was responsible for regulating how B cells (white blood cells that produce antibodies including the allergy-causing IgE antibody, as well as the IgG and IgM antibodies that are involved in many autoimmune diseases) switch from making one antibody to another, a biological process called switch recombination. This first study showed that SWAP-70, thought to be located in the nucleus, was the facilitator of the switching event, which results in the production of antibodies.

The current study shed additional light on the earlier report and found that although switch recombination occurs in the nucleus, SWAP-70 is also found on the cell membrane and is part of the B cell receptor complex where antigens (substances that cause an allergic or immune response) bind to and activate B cells. The binding of antigens to B cells is what triggers activation of switch recombination and ultimately, antibody production. It is now known that SWAP-70 is involved in both the immunoglobulin (antibody) receptor signaling pathway and the control of activation of the switch recombination process, rather than the process itself.

"This is an important discovery because it helps us further understand an important signaling pathway involved in several immunologic diseases," said Donald G. Payan, MD, Rigel's Chief Scientific Officer. "Though there is still much work to be done to further validate SWAP-70 as a drug target, it has important implications because if we could design small molecule compounds that can regulate the activation of switch recombination , we could theoretically control antibody production and selectively block those that lead to disease."

The researchers used Rigel's retroviral expression technology to analyze the function of SWAP-70 and to dissect the pathway in which it is involved. Rigel is currently using its retroviral systems, which are part of the Company's post-genomics combinatorial biology technology, in a number of programs examining the function of B cells. In the area of asthma and allergy, Rigel has been working with its partner Pfizer to identify intracellular drug targets that control and mediate the first step in the production of IgE in B cells -- the switching of immunoglobulin to IgE -- which would essentially stop IgE from being produced. Inhibitors at this step would be very early blockers of the process and therefore be very effective in shutting down the processes that lead to allergic and asthmatic symptoms. B cells are also centrally involved in autoimmune disease, which is characterized by abnormal or overproduction of antibodies resulting in tissue damage. In this area, Rigel has been working with its partner Novartis, on a program to prevent secretion of antibody by activated B cells.

Rigel Pharmaceuticals, Inc., located in South San Francisco, California, is a post-genomics combinatorial biology company focused on discovering novel small molecule drugs based on the Company's rapid drug target identification and validation technology. Rigel currently has nine product development programs underway in the areas of immunology and cancer and has entered into collaboration agreements on six of these programs. The Company is collaborating with: Cell Genesys in the area of cancer gene therapy; Janssen Pharmaceutica, a Johnson & Johnson company, on small molecule oncology diagnostics and therapeutics; Pfizer, Inc. in the area of human and veterinary therapeutics for asthma and allergy; and with Novartis on three different programs in the area of autoimmunity and immunology.