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Nuon Therapeutics, Inc., a privately held, clinical stage biopharmaceutical company, announced today that results from clinical and preclinical studies demonstrating the ability of tranilast to reduce serum uric acid levels and monosodium urate crystal-induced inflammation – two important risk factors for gout – were presented at The European League Against Rheumatism (EULAR) 2010 Annual European Congress of Rheumatology in Rome, Italy, June 16-19, 2010.

Tranilast is an anti-inflammatory agent originally developed in Japan, which is marketed in Asia for asthma, allergic rhinitis, atopic dermatitis and hypertrophic scarring. Nuon Pharmaceuticals, under a license from Kissei Pharmaceutical Co., Ltd., is currently studying the compound, in combination with allopurinol, in its lead program in gout, NU1618.

“These results confirm the potential utility of tranilast as a uricosuric agent while also demonstrating its anti-inflammatory activity that may provide additional therapeutic benefit in the treatment of gout,” said Lee Rauch, president and chief executive officer of Nuon Therapeutics. “Validating earlier clinical observations about tranilast, this research was the basis for our decision to pursue our NU1618 program, which we have now advanced into phase 2b clinical development in hyperuricemia and gout.”

Tranilast Reduces Serum Uric Acid (Abstract #SAT 0369)

In a poster presentation, results were described from a pair of clinical pharmacology studies evaluating the serum uric acid-lowering and uricosuric (excretion of uric acid in the urine) effects of tranilast in healthy subjects with no history of gout and a mean sUA of 5.2 mg/dL.

The first study assessed the effect of a single dose of tranilast in 29 subjects who were randomized to receive placebo or tranilast 100 to 900 mg. Serum uric acid levels (sUA) were measured at 24 hours post administration. Tranilast in doses ranging from 100 to 900 mg administered orally once and twice daily demonstrated a statistically and clinically significant reduction in sUA. After 24 hours, there was a decrease in sUA of 0.24 mg/dL for each 100 mg increase in dose of tranilast (p=0.0001).

The second study examined the effects of tranilast taken once or twice daily for seven days in subjects who were randomized to receive placebo or total daily doses of 300, 600 or 900 mg of tranilast. The study included 46 subjects with a mean sUA of 5.5mL.

There was a clinically and statistically significant reduction in sUA after 7 days. The sUA decreased by approximately 24 percent, 57 percent and 66 percent in the 300, 600 and 900 mg tranilast groups respectively. There was no difference between once- and twice-daily administration.

Collectively, these two studies demonstrate that tranilast has significant urate-lowering properties and supports further development for the potential treatment of hyperuricemia in patients with gout.

In both studies, the most common adverse effect was headache. In the second study, six episodes of elevated liver transaminase were observed among five patients, two episodes among those taking tranilast and four among those taking placebo. These elevations were judged unrelated to tranilast.

Tranilast Suppresses MSU Crystal-Induced Inflammation (Abstract #AB 0054)

A separate abstract compared tranilast to vehicle, colchicine, and indomethacin in a rat air pouch model of inflammatory response to monosodium urate (MSU) crystals. Tranilast produced statistically superior suppression of both leukocyte infiltration and plasma extravasation induced by MSU crystals compared to vehicle. These effects were similar in magnitude to those produced by colchicine and indomethacin. Coupled with the uricosuric effect of tranilast, this anti-inflammatory activity contributes to a unique therapeutic profile in hyperuricemia and gout.

“These findings suggest that tranilast could be an important addition for the treatment of patients with chronic gout,” said Michael Kitt, M.D., executive vice president and chief medical officer of Nuon Therapeutics, Inc. “It is clear that tranilast has significant uricosuric and anti-inflammatory effects.”

About NU1618

Nuon Therapeutics’ lead program, NU1618, is a proprietary combination of tranilast and allopurinol currently in phase 2b development for the treatment of hyperuricemia in patients with gout. Topline results from a completed proof-of-principle, phase 2a study, released earlier this month, demonstrated that the combination produced greater reductions in serum uric acid (sUA) levels in patients with hyperuricemia than either agent alone.

About Hyperuricemia and Gout

Gout is a chronic, progressive rheumatic disease, caused by an inflammatory response to uric acid crystals deposited in joints and soft tissues as a result of an excess of uric acid in the blood (“hyperuricemia”). The most common form of inflammatory arthritis, gout affects approximately 8-10 million people in the United States and Europe. The disease is characterized by acute episodes, or flares, in which uric acid crystals trigger an immune response in the body and produce painful and debilitating inflammation. Gout patients also have a chronic, systemic inflammation as a result of their disease and underlying uric acid crystal burden. This chronic, systemic inflammation associated with gout has been identified as a risk factor for cardiovascular disease. Effective treatment of hyperuricemia in gout patients requires lifelong therapy to decrease uric acid in the body.