Rigel Pharmaceuticals, Inc (SOUTH SAN FRANCISCO, California), a clinical-stage drug development company, provided an update on R788, currently involved in ongoing phase II clinical trials in immune thrombocytopenic purpura (ITP) and rheumatoid arthritis (RA). R788 is a novel oral syk kinase inhibitor that blocks the activation of mast cells, macrophages, and B-cells that promote swelling, inflammatory responses and tissue damage. These activities derive from syk kinase's pivotal role in mediating IgG receptor signaling inside cells.

Rigel commenced an exploratory phase II clinical trial of R788 in January 2007 to evaluate its safety and efficacy in chronic ITP patients. Antibodies, usually of the IgG type, mediate the platelet destruction in ITP. In the trial, R788 was orally administered in doses of 75 mg BID to 125 mg BID for 30 or more days. Preliminary trial data in a number of patients studied demonstrate drug-induced platelet count increases, without discernible issues of safety and tolerability. In addition, in a murine model of ITP, R788 was shown to increase platelet counts significantly. Based on these initial results, Rigel has submitted an amended protocol to the US Food and Drug Administration (FDA) to expand this trial to allow for a greater range of dose regimens and to continue to treat those patients who are responding to R788 beyond 90 days. Rigel expects to receive final results from the study by the end of 2007.

In September 2006, Rigel commenced a phase II, multicenter, randomized, double-blind, placebo-controlled, dose-ranging clinical trial to evaluate up to three doses of R788, in combination with methotrexate (MTX), in RA patients for 90 days. Rigel has completed the first-dose group (50 mg BID) and is currently enrolling patients in the second-dose group (100 mg BID). To date, R788 appears to be well tolerated in the first-dose group. To expedite patient recruitment, Rigel has recently added additional clinical sites and expects to receive results from the completed clinical trial in the second half of 2007.

In preclinical studies, R788 was shown to diminish the swelling and tissue destruction associated with RA. In the phase I trial, R788 was well tolerated and showed good pharmaceutical properties when administered both alone and in combination with MTX in RA patients.

Also of interest is Rigel's investigational drug R348, a selective, potent inhibitor of Janus Tyrosine Kinase 3 (JAK3), which is critical to immune system activation. JAK is an attractive target because its expression is limited to key cells in the immune system, particularly the T-cell, and is activated by multiple cytokines, including IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. In preclinical animal models, R348 was well tolerated and preclinical development should be completed soon. Rigel plans to file an Investigational New Drug (IND) application with the FDA in the second half of 2007. Initially, R348 will target RA but the company expects to explore the use of R348 in psoriasis, transplant rejection, and graft-versus-host disease.

—A. Techman

E-mail any comments to .