Comparative Phase II Clinical Trial of R112 for Allergy Treatment

Rigel Pharmaceuticals, Inc today announced that it has enrolled the first patient in a comparative Phase II clinical study of R112, a potential intranasal therapy for the treatment of allergic rhinitis. Allergic rhinitis causes chronic congestion and general inflammation of the upper respiratory tract in more than 59 million people in the United States. R112 inhibits mast cell activation and thereby blocks the major pathways triggered in an allergic attack. This trial, which is expected to enroll approximately 375 patients, will be a randomized, double-blind study comparing R112 to placebo and Beconase AQ(R) (beclomethasone) nasal spray over a 7-day period.

"The purpose of this trial is to verify the safety and efficacy of R112. We want to confirm that R112 is significantly superior to placebo for the treatment of allergic rhinitis and compare it with a nasal steroid," stated Elliott B. Grossbard, M.D., senior vice president of Medical Development at Rigel.

"Our initial Phase II 'Park' study demonstrated that R112 could improve allergy symptoms, including sneezing, stuffy nose, running nose, itchy nose and throat, post nasal drip, cough, headache and facial pain, in as early as 30 minutes, whereas steroids typically take longer. Furthermore, the magnitude of effect increased over time. We are hopeful that this next study will also show that R112 could be a significant addition to current therapies."

The Phase II trial will enroll patients that have experienced seasonal allergic rhinitis during the summer/fall pollen season for the last two years.

The primary endpoints are safety and efficacy, as measured by a total nasal symptom severity (TNSS) rating scale, a scale of five nasal symptoms including congestion, runny nose, sneezing, itchy nose and postnasal drip.

The trial consists of a screening period during which the patients must stop taking any allergy medications, followed by a placebo run-in period. The patients are then randomized to a 7-day treatment cycle of R112, placebo or Beconase AQ(R).

Approximately 25 sites across the U.S. are participating in the trial. Results are expected in the fourth quarter of this year.

"The allergy market represents a huge opportunity for a fast-acting, novel therapeutic," said James M. Gower, chairman and chief executive officer of Rigel. "There has been very little innovation in this field in recent years, despite the fact that so many people suffer from the debilitating symptoms associated with allergies."

Allergic Rhinitis: Role of Immune Mediators and Current Treatments Allergic rhinitis involves inflammation of the mucous membranes of the nose, eyes, ear, sinuses and pharynx. This inflammation is characterized by a complex interaction of inflammatory mediators, but ultimately is triggered by an immunoglobulin E (IgE)-mediated response to a foreign allergen.

When a specific allergen (e.g., pollen) is inhaled into the nose, it can bind to the IgE on mast cells present in the mucus membranes. This leads to immediate and delayed release of a number of mediators, which can ultimately lead to common allergic symptoms such as nasal congestion, sneezing, itching and rhinorrhea. These mediators include histamine, tryptase, chymase, kinins, heparin, leukotrienes and PGD2.

Common allergy drugs such as antihistamines or antileukotrienes block only a single mediator. Intranasal steroids are able to block multiple mediators in the allergic response, but these have a slow onset of action and sometimes require multiple days of treatment before a positive effect is seen. Despite the drawbacks of these treatments, the U.S. market for allergic rhinitis therapies approaches $4 billion.(1)

R112 and its Mechanism of Action

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. R112 binds to an intracellular target (syk, a kinase that regulates IgE receptor signaling) in mast cells and interrupts the signal from the IgE receptor, thus preventing cellular activation and subsequent chemical mediator release. In the Phase II 'Park' study, R112 significantly diminished both the acute and chronic symptoms of allergic rhinitis, such as sneezing, itchy nose, nasal congestion, cough and facial pain, underscoring the correlation of beneficial clinical outcomes and R112's broad mechanism of action. In the Phase I/II trial completed in 2003, R112 began to diminish chemical mediator release within minutes after allergen challenge. R112 is delivered intranasally, and no systemic exposure to R112 has been detected in any intranasal administration in any human trials to date.

About Rigel

Rigel's mission is to become a source of novel, small-molecule drugs to meet large, unmet medical needs. We have three product development programs: asthma/allergy, rheumatoid arthritis and cancer. Our strategy is to commence clinical trials with one lead compound each year and to develop a portfolio of product candidates for our own proprietary programs and with potential collaborative partners.

This press release contains "forward-looking" statements, including statements related to Rigel's plans to pursue clinical development of product candidates and the timing thereof and the potential efficacy of product candidates. 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 pre-clinical studies and clinical trials, 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, 2005. Rigel does not undertake any obligation to update forward-looking statements.

NOTE: Beconase AQ is a registered trademark of GlaxoSmithKline.

(1) Decision Resources, Inc.

Rigel Pharmaceuticals, Inc.
http://www.rigel.com