press release archive

Rigel Initiates Clinical Trial in Hepatitis C

Trial Designed to Establish Safety of R803

South San Francisco, CA - November 12, 2003

Rigel Pharmaceuticals, Inc. (NASDAQ: RIGL) today announced that it has initiated an escalating single dose safety trial of R803, an experimental drug to treat the hepatitis C virus (HCV). The goal of this trial is to establish the safety and pharmacokinetics of R803. Results of this trial are expected in January 2004, and, if successful, will allow Rigel to enter into phase I/II efficacy trials in the United States in the first half of 2004.

R803, Rigel’s oral, small-molecule, anti-HCV compound, is a non-nucleoside HCV polymerase inhibitor. Based on preclinical data, Rigel believes that R803 is potent, selective, rapidly inhibits viral replication and is active against all genotypes of HCV. Moreover, as a result of R803’s unique viral binding site, resistance may be slow to develop. R803 is extremely potent at inhibiting viral replication, with an EC50 (the concentration of the drug necessary to produce a 50% inhibition of viral replication) in the low nanomolar range, as assessed both in a replicon system and in a live virus assay. Pre-clinical testing completed to date shows no significant adverse effects attributed to R803 at the clinical dose levels. Evaluated across numerous human cell lines, the compound does not appear to interfere with normal cellular functions, including DNA, RNA and protein synthesis, cell signaling and immune cell activation and function. In assays using live virus, R803 appears to act within days to reduce viral levels significantly.

“R803 has shown significant potential as a potent therapeutic agent that rapidly inhibits viral replication,” said Dr. Donald G. Payan, Rigel’s co-founder and Chief Scientific Officer. “This is one of the first direct hepatitis C anti-virals to enter human clinical trials and, if proven safe and effective, we believe that it could dramatically improve the treatment of this serious disease.”

HCV: Current Treatments and Market Opportunity
Hepatitis C is an inflammation of the liver caused by the hepatitis C virus. As the most common blood-borne infection in the United States, HCV affects 4 million Americans and 170 million individuals worldwide. Approximately 85% of those with acute illness will go on to develop chronic hepatitis, a condition that has been linked to cirrhosis, hepatocellular carcinoma (liver cancer) and liver failure. HCV accounts for 30% of end-stage liver disease and liver cancer and is the leading cause of liver failure, which can result in the need for liver transplantation. Public health officials in the United States and abroad have mobilized to address this medical crisis by identifying detection guidelines for HCV and implementing therapies to eradicate chronic infection.*

Currently available HCV therapies are only modestly effective at treating the disease. The most prevalent treatment regimen is with interferon alpha (IFNa), usually in combination with ribavarin. IFNa shows only a 20% to 40% success rate in patients who complete therapy, and significant side effects result in up to half the patients either quitting treatment or moving to a lower dose regimen. Moreover, IFNa is least effective against HCV genotype 1, the strain responsible for 70% of chronic HCV infection cases in the United States, as compared to its effectiveness against other HCV genotypes. Rigel believes that its approach is substantially different than that of IFN: instead of working to boost the immune system, R803 rapidly, selectively and potently targets HCV by interfering with a viral polymerase protein that is needed for replication. In preclinical assays, R803 has demonstrated effectiveness against all major genotypes.

With the current high prevalence and projected increase in cases of HCV and related diseases, and with the limited success of currently available therapies, Rigel believes that the potential for new direct HCV therapeutics is large and that R803 has the potential to be at the forefront of this opportunity.

Rigel HCV Analyst/Investor Briefing
Rigel will host an analyst/investor day on Wednesday, November 19, 2003, at 10:00 a.m. Eastern Time at the W Hotel in New York City. The day will be devoted to the topic, “Hepatitis C: Treatment, Progress and Opportunities.” Featured speakers will include: Jules L. Dienstag, M.D., Professor of Medicine and Associate Dean for Academic and Clinical Programs, Harvard Medical School; Charles M. Rice, Ph.D., the Maurice R. and Corinne P. Greenberg Professor and Head of the Laboratory of Virology and Infectious Disease, The Rockefeller University; and Rigel senior management. For additional information, or to RSVP for the analyst day, please email: hepc@rigel.com; call: 650-624-1181; or visit Rigel’s website: http://www.rigel.com/hepc. A live and archived audio webcast will be available by going to Rigel’s website and following the links from the homepage.

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. Rigel has begun clinical testing of its first two product candidates, R112 for allergic rhinitis and R803 for hepatitis C, and plans to begin clinical trials of two additional drug candidates, for the treatment of rheumatoid arthritis and asthma, by the end of 2004.

This press release contains “forward-looking” statements, including statements related to Rigel’s strategic goals, the timing and subject matter of future clinical trials and the properties, efficacy and potency of compounds such as R803. 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,” “expects,” “believes” and similar expressions are intended to identify these forward-looking statements. There are a number of important factors that could cause Rigel’s results and plans 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.

* Source: New England Journal of Medicine, 341(8):556-62, 1999

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

Media Contact:
Melinda Bagatelos or Ayanna Smith, 415-512-0770, rigel@schwartz-pr.com