Gout Market Opportunity Overview

• An estimated 3-5 million people in the U.S. and approximately 5 million people in the European Union suffer from gout, which is the most common form of inflammatory arthritis in men over 40
• There have been no new therapies approved by the U.S. Food and Drug Administration for the treatment of hyperuricemia associated with gout in the past 40 years
• Marketing authorization was recently granted in the European Union for febuxostat (Adenuric, Ipsen Manufacturing Ireland Limited), a non-purine selective inhibitor of xanthine oxidase that has been associated with serious cardiovascular adverse events in clinical trials.

Gout, also known as metabolic arthritis, is a painful and debilitating disease caused by abnormally elevated levels of uric acid in the blood stream. These abnormally elevated levels lead to the deposition of uric acid crystals in and around the connective tissue of the joints and in the kidneys, leading to inflammation, the formation of disfiguring nodules (tophi), intermittent attacks of severe pain (acute flares), and kidney damage (nephropathy). While gout is a treatable condition, there are limited treatment options, and a number of adverse effects are associated with current therapies. In addition, evidence suggests that the chronic elevation of uric acid associated with gout, known as hyperuricemia, may also have systemic consequences, including an increased risk for kidney dysfunction and cardiovascular disease.

RDEA594, our lead product candidate for the treatment of hyperuricemia and gout, currently in Phase 1 clinical development, is a major metabolite of RDEA806, our lead NNRTI in clinical development for the treatment of HIV. RDEA594 does not have antiviral activity and is responsible for the uric acid-lowering effects observed following administration of RDEA806 to over 150 subjects in Phase 1 and Phase 2 clinical trials. Preliminary data from a Phase 1 ascending dose study in healthy volunteers show that oral administration of 100 mg of RDEA594 demonstrated a favorable pharmacokinetic profile with low systemic clearance, favorable absorption and half-life supporting once-daily dosing. Additionally, 100 mg of RDEA594 produced a significant increase in urinary excretion of uric acid, confirming that it is responsible for the uric acid-lowering effects observed in pervious clinical studies of RDEA806.

Based on extensive in vitro and in vivo experiments, we believe that RDEA594 exhibits a concentration-dependent inhibitory effect on the URAT1 transporter-mediated uptake of uric acid. Approximately 90% of hyperuricemic patients are considered to be under-excretors of uric acid, so increasing excretion may provide the most physiologically appropriate treatment.

Our second-generation URAT1 inhibitors include a broad range of compounds from several distinct chemical classes, representing new chemical entities that we are currently evaluating as potential future product candidates.

For more information regarding these programs please click here to view our most recent company presentation.