Veterans Blvd. South San Francisco, CA 94080 Main Phone: 650.624.1100 FAX: 650.624.1101 http://www.rigel.com R788 in TASKi3 Clinical Trial Does Not Meet Efficacy Endpoints in RA Patients Who Had Previously Failed Biologi

R788 in TASKi3 Clinical Trial

Does Not Meet Efficacy Endpoints in RA Patients Who Had Previously Failed

Biologic Therapies Results Incongruent

Bone MRI Scans Show Improvement; Safety Results Consistent with TASKi2

SAN FRANCISCO, Calif., July 23, 2009 Rigel Pharmaceuticals, Inc.

(Nasdaq: RIGL) today announced that in the TASKi3 Phase 2b clinical trial in

rheumatoid arthritis (RA) patients who had failed to respond to at least one

biologic treatment, the group treated with R788 (fostamatinib disodium) did not

report significantly higher ACR 20, ACR 50, ACR 70 and DAS28 response rates

than the placebo group at three months, and therefore, the trial failed to meet

its efficacy endpoints. The objective components (CRP and ESR)* of these ACR

scores did show a statistically significant difference; however, the subjective

reported response rate components did not as compared to placebo. Although the

ACR scores for the R788 group were within the expected range in this patient

population, the reported placebo response rates were considerably higher than

seen in any other previous study of RA biologic failure patients and rose unaccountably

between week 6 (at which point the reported response rates between R788 and

placebo were significantly different) and month 3 (when such reported response

rates were no longer significantly different).

was the first clinical trial evaluating R788 in which anatomical changes in the

patients wrist and hands were evaluated using Magnetic Resonance Imaging (MRI)

and scored using the RAMRIS (Rheumatoid Arthritis Magnetic Resonance Imaging

Scoring) system. Those results showed

improvements in the treated group versus the placebo group in the Synovitis and

Osteitis scores, while the Erosion scores, known to be the slowest to change,

showed no significant effect at three months. The most frequent adverse events

were as expected from the earlier TASKi trials and appear to be manageable.

will host a conference call today at 7PM EDT/ 4PM PDT to discuss these results

(see conference call details below).

objective with R788 in RA is to position the product after methotrexate and

before biological therapies are used. We

have shown excellent results in that patient population in our earlier TASKi1

and TASKi2 studies, and we believe that patient population represents the large

market opportunity for this product, said James M. Gower, chairman and chief

executive officer of Rigel. In this

TASKi3 patient population, biologic failures, we have seen divergent results as

sometimes happens in studies with subjective components. However, we are pleased to see excellent

results in the objective measures and in the Synovitis and Osteitis MRI

*blood measurements of C-Reactive Protein

(CRP) and Erythrocyte Sedimentation Rate (ESR)

At 3 months. All patients were on stable doses of methotrexate throughout the

Mean Change from Baseline in RAMRIS* Scores at Month 3

is a rheumatoid arthritis scoring system utilizing magnetic resonance imaging

to evaluate abnormalities (synovitis, bone edema and bone erosion) in the hands

and wrists. The system was developed by

OMERACT, (Outcome Measurements in Rheumatology) in 2002, and has become a

global standard measurement of inflammation and destruction in those joints.

For these scores a lower value indicates a better clinical condition.

inflammation of the synovial membrane lining joints Osteitis: inflammation of

to TASKi2, the most common clinically meaningful drug-related adverse events

noted in TASKi3 were diarrhea and hypertension.

Dose reduction options were pre-specified in the trial protocol and, in

cases where doses were reduced, patients generally completed the clinical trial

with minimal safety issues. The most common adverse events in the trial overall

were related to infections, though these were generally evenly distributed

among the placebo and active dose group.

mean increase in blood pressure from baseline at 3 months, using a last

observation carry forward methodology, was 3.2-3.6 mmHg for the 100 mg bid dose

group. In TASKi3, approximately 17% of patients in the 100 mg bid dose group

had blood pressure medication adjusted or in some cases initiated during the

course of the clinical trial, compared to 8% of the placebo patients. For those patients who had their dose of

blood pressure medications adjusted or initiated, their blood pressure was

successfully reduced and their blood pressure was generally well controlled

throughout the trial. The blood pressure

medications were standard doses of common blood pressure medications such as

ACE inhibitors or diuretics.

this patient population, patients who failed biologic therapies, their bones

and joints appear to respond to R788, but the objective and subjective

components of the ACR and DAS28 scores are incongruent, mainly because the

reported subjective placebo response rates were higher than expected, said

Elliott Grossbard, M.D., chief medical officer for Rigel. Nonetheless, R788 is

well tolerated and its side effects appear generally manageable, and we look

forward to planning our Phase 3 program for R788 with a corporate partner, he

Treatment Emergent Adverse Events

Blood Pressure (Systolic/Diastolic in mmHg)

was a 3 month, multi-center, randomized, double blind, placebo controlled,

parallel dose clinical trial involving 219 RA patients in the U.S. who had

failed to respond to at least one biologic treatment (such as TNF

inhibitors). The patients were randomly

assigned to two cohorts and thus received R788 orally in a 100 mg bid (twice

daily) dose or placebo for a period of up to 3 months. Patients were assigned on a 2:1 basis to R788

or placebo. Throughout the clinical

trial period, all of the patients continued to receive their stable dose of

assessments for each participant were based on the American College of

Rheumatology criteria, which denotes at least a 20% (ACR 20) improvement, at

least a 50% (ACR 50) improvement, or at least a 70% (ACR 70) improvement, from

the baseline assessment at the end of the 3 month treatment period. The ACR

measurement factors included reported physician and patient global assessment

of disease activity, patient reported pain score, and any change in CRP in the

patient s blood. The primary efficacy endpoint for the clinical trial was the

percent of patients assigned to the R788 100 mg bid dose who were ACR 20

responders at the end of 3 months.

Secondary efficacy endpoints included other ACR scores and, a comparison

of response rates for the R788 100 mg bid dose versus placebo as determined by

MRI using the modified RAMRIS scoring system of wrists and hands at baseline