SAN DIEGO, June 11 /PRNewswire-FirstCall/ -- Ardea Biosciences, Inc. today announced that data will be presented on the Company’s lead mitogen-activated ERK kinase (MEK) inhibitor, RDEA119, demonstrating its potent activity in animal models of arthritis. In addition, the Company will present data on the mechanism of action for RDEA806 and RDEA594 in the area of gout. These data will be presented tomorrow at the 2008 Annual European Congress of Rheumatology Organized by the European League Against Rheumatism (EULAR) in Paris, France.
The extracellular signal-regulated kinase (ERK) pathway plays a critical role in the control of cellular activation, proliferation and the production of inflammatory mediators. Suppression of the ERK pathway by inhibitors of MEK1/2 represents a potential therapeutic approach for treating chronic inflammatory diseases such as rheumatoid arthritis. RDEA119 is a novel selective MEK1/2 inhibitor that was shown to produce a significant beneficial effect in three different animal models of arthritis:
“We are making excellent progress in all of our inflammation programs. To support the development of RDEA119 in inflammatory diseases, we are currently conducting a Phase 1 proof-of-concept trial in healthy volunteers, which we expect to complete in the second half of this year,” said Barry D. Quart, PharmD, Ardea Biosciences’ President and CEO. “In addition, we are on track to begin two gout trials, a Phase 1 trial with RDEA594 in the second half of this year and a Phase 2 proof-of-concept trial with RDEA594’s prodrug, RDEA806, in the third quarter of this year.”
Analysis of two Phase 1 healthy volunteer studies of the Company’s lead NNRTI candidate, RDEA806, revealed statistically significant reduction of serum uric acid (sUA) compared to placebo. In order to further understand the mechanism responsible for the sUA lowering effect, extensive experiments were conducted. Based on these studies, RDEA594 was identified as a major metabolite of RDEA806 in both humans and animals. RDEA594 exhibits a concentration-dependent inhibitory effect on the URAT1-mediated uptake of uric acid ex vivo and increases uric acid excretion in animal models. These findings suggest that RDEA594’s effect on both the uptake and excretion of uric acid is responsible for essentially all of the uric acid lowering effects seen with its prodrug, RDEA806.
About RDEA119
RDEA119, a non-ATP competitive, highly-selective MEK inhibitor for the treatment of inflammatory diseases and cancer, is the Company’s lead compound from its MEK inhibitor research and development program. RDEA119 has shown potential as a potent inhibitor of MEK, which is believed to play an important role in inflammation, as well as cancer cell proliferation, apoptosis and metastasis. Preclinical and clinical results suggest that RDEA119 has favorable properties, including oral dosing, excellent selectivity and limited retention in the brain, which, in turn, may result in a reduced risk of central nervous system (CNS) side effects. The Company is also investigating a second generation MEK inhibitor, RDEA436, for potential use in inflammatory diseases and cancer. Preclinical data suggest that RDEA436 is a potent inhibitor of MEK and may have favorable properties, such as low CNS penetration. In addition, RDEA436 has demonstrated a long half-life in a human micro-dose pharmacokinetic study, with the potential for once daily dosing in humans.
About RDEA594
RDEA594 is a development candidate that has potential for treating gout patients with hyperuricemia. RDEA594 is a metabolite of RDEA806, a non-nucleoside reverse transcriptase inhibitor (NNRTI) in development for the treatment of HIV. In Phase 1 studies with RDEA806 in healthy volunteers, increased urinary excretion of uric acid was observed in the first 24 hours after dosing, with statistically significant, exposure-dependent, decreases in serum uric acid of 35% to 50% observed following 10-14 days of dosing. RDEA594 exhibits a concentration-dependent inhibitory effect on the URAT1-mediated uptake of uric acid ex vivo and is believed to be responsible for the uric acid-lowering effects of RDEA806. Approximately 90% of hyperuricemic patients are considered to be under-excretors of uric acid, so increasing excretion may provide the most physiologically appropriate treatment. RDEA594 does not have significant antiviral activity.
About Ardea Biosciences
Ardea Biosciences, Inc., of San Diego, California, is a biotechnology company focused on the discovery and development of small-molecule therapeutics for the treatment of HIV, cancer and inflammatory diseases, including gout. We have four drug candidates in clinical trials and others in preclinical development and discovery. Our most advanced development candidate is RDEA806, a non-nucleoside reverse transcriptase inhibitor (NNRTI), which is in a Phase 2a study for the treatment of HIV. We have evaluated our second-generation NNRTI for the treatment of HIV, RDEA427, in a human micro-dose pharmacokinetic study and have selected it as a development candidate. RDEA594, our lead development candidate for the treatment of gout, is in preclinical development and is believed to be an inhibitor of the URAT1 transporter in the kidney, which is responsible for regulation of uric acid levels. We are evaluating our lead MEK inhibitor, RDEA119, in a Phase 1 study in advanced cancer patients, as well as in a Phase 1 study in normal healthy volunteers as a precursor to trials in patients with inflammatory diseases. Lastly, we have evaluated our second-generation MEK inhibitor for the treatment of cancer and inflammatory diseases, RDEA436, in a human micro-dose pharmacokinetic study and have selected it as a development candidate.
Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements regarding our goals, including the expected properties and benefits of RDEA806, RDEA427, RDEA594, RDEA119, RDEA436 and our other compounds and the results of preclinical, clinical and other studies. Risks that contribute to the uncertain nature of the forward-looking statements include: risks related to the outcome of preclinical and clinical studies, risks related to regulatory approvals, delays in commencement of preclinical and clinical studies, and costs associated with our drug discovery and development programs and business development activities. These and other risks and uncertainties are described more fully in our most recently filed SEC documents, including our Annual Report on Form 10-K and our Quarterly Reports on Form 10-Q, under the headings “Risk Factors.” All forward-looking statements contained in this press release speak only as of the date on which they were made. We undertake no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.
CONTACT: Edie DeVine of WeissComm Partners, +1-415-946-1081, for Ardea
Biosciences, Inc.
