A3384

We are developing A3384 to treat bile acid malabsorption disease (BAM), a disease with no approved treatment options. A3384 is a proprietary formulation designed to selectively release a drug known as cholestyramine directly to the colon to enhance its safety and tolerability and improve patient benefit.

Cholestyramine is a bile acid sequestrant that acts by binding to bile acids in the GI tract to create insoluble complexes that are more easily secreted. These complexes replace bile acids that would otherwise stimulate electrolyte and water secretion in the small bowel and lead to diarrhea. Cholestyramine is approved in the United States (as well as Japan and many countries in Europe) as an adjunctive therapy to diet for the reduction of elevated serum cholesterol in certain patients and for the relief of pruritus associated with partial biliary obstruction, and we believe that it is commonly prescribed to treat BAM. Cholestyramine is typically taken as a powder that does not dissolve in water and has been described as “drinking sand.” As a result, many patients cannot tolerate cholestyramine and its benefit in the treatment of BAM has been limited.

We believe that a formulation that has a more favorable tolerability profile than conventional bile acid sequestrants can benefit patients with BAM. In a Phase 2 study, an A3384 prototype showed encouraging signals of efficacy for symptoms of BAM and was generally well tolerated. A successful optimization program has resulted in an improved formulation positioned for a clinical study.