Gaucher disease is the most prevalent lysosomal storage disorder, with an estimated incidence of 1 in 40,000-50,000 in the general population and 1:800 among the Ashkenazi Jewish population. Gaucher disease can lead to liver and spleen enlargement, anemia, painful bone lesions and in some cases neurological damage. Gaucher disease results from an accumulation of glucosylceramide in macrophage lysosomes due to deficiencies in the enzymatic activity of lysosomal GCase.

Gaucher disease is further categorized into three clinical subtypes: Type I - Chronic Non-neuronopathic, Type II - Acute Neuronopathic and Type III - Subacute Neuronopathic. The most frequently occurring subtype, Type I, accounts for 98% of affected Ashkenazi Jews and 56% of affected non-Jews. Symptoms of Type I usually appear in adulthood. These include enlarged spleen and liver, anemia, low platelet counts and fractures and bone pain. Patients do not experience the neurological features associated with Types II and III. The clinical severity of Type I is extremely variable, some patients experiencing the full range of symptoms, while others remain asymptomatic throughout most of their lives. Type II symptoms typically appear by three months of age with rapid neurodegeneration, extensive visceral involvement and death before two years of age (typically due to respiratory complications). The clinical presentation in Type II is typically more uniform than that of Type I. Type III symptoms can appear either in infancy or early childhood, with neurological, visceral and bone complications. Although disease severity can vary widely, progression is typically slower than Type II.

The prevalent form of treatment currently available involves enzyme replacement therapy with recombinant GCase (Cerezyme, Genzyme Corporation). We believe that the use of EXR-202 for Gaucher disease patients who respond to the drug may have advantages relative to the use of Cerezyme. Animal studies show that EXR-202 is well distributed throughout the body and can cross the blood brain barrier. Because Cerezyme is a large protein molecule, it is believed to have difficulty penetrating some tissue and cell types. In particular, it is widely believed that Cerezyme is unable to cross the blood brain barrier and thus unlikely to address the neurological symptoms of Type II and Type III Gaucher disease. Cerezyme treatment is inconvenient in that it requires intravenous infusions, typically on a bi-weekly basis. Oral treatment with EXR-202 is more convenient avoids the health risks of frequent intravenous infusions.