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Unmet Needs

CymaBay Therapeutics is focused on developing therapies to treat serious rare and orphan metabolic diseases or more prevalent diseases with high unmet medical need. These diseases represent a worldwide health problem and a significant source of morbidity, mortality and health care costs in the United States and abroad. We seek not only best-in-class approaches, but also first-in-class compounds that address these unmet needs in novel ways.


Gouty arthritis, or simply gout, is the most common form of inflammatory arthritis and affects more than 8 million people in the United States. The hallmark symptom of gout is a flare, characterized by debilitating pain, along with tenderness and inflammation of affected joints. Gout has a significant impact on patients' quality of life and health care utilization. During acute attacks, patients are frequently bedridden and require time away from work. Patients experiencing gout flares miss an average of 4.6 more days of work per year than those without gout. Gout flares also result in increased health care utilization with approximately 35% of moderate and 50% of severe gout patients who experience a flare having at least one acute care visit per year. Of the 8 million patients with gout in the US, 3 million are on urate lowering therapy (ULT). Despite being on ULTs, about 1 million patients will continue to experience 3 or more flares per year, with significant impact to patient quality of life and the health care system. According to a 2012 study, patients having 3 or more flares per year typically incur more than $10,000 in annual health care costs compared to patients without gout. In order to halt the progression of the disease and provide long term reduction in flares, monosodium urate (MSU) crystals must be eliminated from the body. Therefore, the twin goals of gout treatment are to prevent flares while lowering sUA to below 6 mg/dL in order to dissolve MSU crystals present in tissue. The most important limitation in achieving these goals is that all existing ULTs paradoxically cause an increase in flares upon initiation of treatment, leading many patients to discontinue or avoid therapy. Non-adherence to therapy is a significant problem. In one long term study, only about 40% of patients reaching the goal of sUA < 6 mg/dL and consequently results in continued flaring and progression of the disease.

CymaBay is developing arhalofenate which has potential to address both unmet needs in gout, decrease painful flares while lowering sUA, through its dual mechanism of action.

Orphan and Rare Diseases

Homozymogous Familial Hypercholesterolemia (HoFH) is a rare, life-threatening, genetic disease characterized by marked elevations in plasma levels of LDL-C leading to severe atherosclerosis and the development of premature cardiovascular diseases. While normal LDL-C levels are approximately 100 mg/dL, patients with HoFH may have levels in the 500 to 1000 mg/dL range. Symptomatic cardiovascular disease often presents during the first decades of life leading to myocardial infarction, ischemic stroke, and death. If untreated, the mean age of death for HoFH patients is in the 30s. Initial treatment of HoFH entails adoption of a low fat diet and exercise program, usually with limited effectiveness. This is followed by conventional pharmacological therapies for reducing LDL-C, including statins, cholesterol absorption inhibitors and bile acid sequestrants. Unfortunately, these conventional therapies work largely through up-regulation of the LDL-R. Thus, they are minimally effective in patients with HoFH in whom LDL-R activity is impaired or absent. Patients having a small amount of residual LDL-R activity may receive a modest reduction in LDL-C with maximal conventional therapy, but most patients with HoFH respond insufficiently. Two new drugs (Juxtapid® and Kynamro®) have recently been approved for use in combination with diet, exercise and conventional lipid lowering therapy to treat HoFH. While these two newly registered drugs offer additional treatment options for patients with HoFH, there remains a high degree of unmet medical need in HoFH. Even with an aggressive combination of available therapies, subjects with HoFH generally have LDL-C levels substantially above treatment targets.

CymaBay is developing MBX-8025 for HoFH and potentially other serious rare and orphan diseases.


Diabetes is a worldwide health problem and a rapidly growing source of illness, death, and health care costs. According to the International Diabetes Federation, approximately 246 million adults, or 6 percent of the world's adult population, had diabetes in 2007. The American Diabetes Association estimates that there were approximately 25.8 million people in the United States with diabetes in 2011, making up 8.3 percent of the population. According to estimates from the ADA, one out of every five health care dollars is spent caring for someone with diagnosed diabetes, while one in ten health care dollars is attributed to diabetes. Total estimated costs of diagnosed diabetes have increased 41%, from $174 billion in 2007 to $245 billion in 2012. Type 2 diabetes accounts for 90 to 95 percent of diabetic cases.

CymaBay is developing MBX-2982 which is a potential first-in-class treatment for type 2 diabetes that targets G protein-coupled receptor 119 (GPR 119), a receptor that interacts with bioactive lipids known to stimulate glucose-dependent insulin secretion.