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Rigel Initiates Multi-Dose Safety Trial of R112 for Allergic Rhinitis

Trial Designed to Establish Safety of R112 for Longer-Term Use

South San Francisco, CA - September 10, 2003

Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) today announced that it has initiated a multi-dose safety trial of R112, an experimental drug to treat allergic rhinitis. The goal of this trial is to establish the longer-term, multi-dose safety of R112 in various dosing regimens. Results of this trial are expected by January 2004 and will allow Rigel to enter into broader, longer-term, multi-dose efficacy trials in the first half of 2004.

In late July, Rigel released the results of a Phase I/II study which evaluated the efficacy and safety of a single intra-nasal administration of R112 in volunteers with asymptomatic seasonal allergic rhinitis. The study demonstrated significant improvement or consistent positive trends in reducing the release of chemical mediators involved in mast cell activation, one of the earliest steps in the initiation of an inflammatory response in allergy and asthma. Additionally, with only a single dose of R112, a correlation between reductions in key mediators and improvements in some allergy symptoms was established. No clinically significant adverse effects were attributed to R112 during this trial or any prior clinical trial.

“R112 may offer a new, comprehensive treatment strategy for allergic inflammation by potentially blocking all major chemical mediators of inflammation involved in mast cell responses and may provide an important, potentially first-line drug, for the treatment of allergic rhinitis.” said Donald Payan, MD, Rigel’s Chief Scientific Officer and Executive Vice President.

“The multi-dose safety trial is an important next step in the development of this drug and is an indicator of our belief in its potential,” said Elliott Grossbard, MD, Rigel’s Senior Vice President of Medical Development.

How R112 Works and Its Possible Advantages
R112 enters mast cells, binds to an intracellular target and interrupts the signal from the IgE receptor, thus preventing downstream signaling and subsequent chemical mediator release. However, unlike common allergy drugs such as antihistamines or antileukotrienes that block only a single mediator, R112 is designed to block all of the major pathways that are triggered in an allergic attack, potentially making R112 a more effective and comprehensive drug. Currently, steroids are the major class of drugs that are able to block multiple mediators in the allergic response, but these have a slow onset of action. In the Phase I/II trial, R112 began to diminish chemical mediator release within minutes after allergen challenge. In addition, steroids need to be used selectively due to their global blocking of immune function. R112 is delivered intra-nasally and no systemic exposure of R112 has been detected in any intra-nasal administration in the two human trials conducted.

About the Allergic Rhinitis Opportunity
The market for drugs aimed at allergic rhinitis is potentially very large, as allergic rhinitis is the most common allergic condition and is increasing in prevalence. Currently, allergic rhinitis afflicts over 150 million people in North America, Europe and Japan alone. This condition is treated most often with inhaled steroids and antihistamines. Sales of these products exceed $2 billion annually in the U.S. Rigel believes that, if shown to be safe and effective, R112 could become the agent of first choice in treating allergic rhinitis, supplanting both steroids and single chemical mediator inhibitors (antihistamines or antileukotrienes) among allergic rhinitis sufferers.

About IgE and the Allergic Cascade
Allergic rhinitis and asthma are chronic inflammatory disorders of the airways. Upon exposure to allergens, such as pollen, an allergic response is triggered resulting in inflammation and airway obstruction. In some patients, allergens such as pollen trigger the production of IgE antibodies that then circulate in the blood. IgE antibodies bind to mast cells and cross-link with their receptors, causing an intracellular signal that results in the release of various chemical mediators, including prostaglandins, tryptase and histamine. When this process occurs repeatedly over time, it creates persistent inflammation of the airway passages, resulting in the chronic congestion and airway obstruction associated with allergic rhinitis and asthma, respectively.

About Rigel (www.rigel.com)
Rigel’s mission is to become a source of novel, small-molecule drugs to meet large, unmet medical needs. Rigel has identified three lead product development programs: mast cell inhibition to treat immunologic diseases such as asthma/allergy and autoimmune disorders, antiviral agents to treat hepatitis C, and ligases, a new class of cancer drug targets. In addition to the clinical testing of R112, Rigel plans to begin clinical trials of three additional drug candidates, for the treatment of hepatitis C, rheumatoid arthritis and asthma by the end of 2004.

This press release contains “forward-looking” statements, including statements related to the safety and efficacy of R112, Rigel’s plans to pursue clinical development of R112 and the potential market for R112. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Words such as “plans,” “intends,” “expects” and similar expressions are intended to identify these forward-looking statements. There are a number of important factors that could cause Rigel’s results to differ materially from those indicated by these forward-looking statements, including risks associated with the timing and success of clinical trials and the commercialization of product candidates, as well as other risks, detailed from time to time in Rigel’s SEC reports, including its Quarterly Report on Form 10-Q for the quarter ended June 30, 2003 and Annual Report on Form 10-K, as amended, for the year ended December 31, 2002. Rigel does not undertake any obligation to update forward-looking statements.

Rigel Contact: Raul Rodriguez (1-650-624-1302)