Through extensive research on how antisense drugs distribute throughout the body, Isis scientists have identified the organs in the human body that accumulate antisense drug at low doses. Isis is concentrating its drug discovery efforts on molecular disease targets found in the liver, kidney, spleen, lymph nodes, bone marrow and fat cells. The Company is focusing its scientific research programs on key therapeutic areas where antisense drugs may offer a treatment advantage. Isis’ drug development programs are aimed at treating cardiovascular, metabolic and inflammatory diseases.  Isis’ partners are focused in disease areas such as ocular, viral and neurodegenerative diseases, and cancer.

Latest Advance:
Advances made in cardiovascular and metabolic disease franchises are examples of the efficiency of antisense drug discovery and demonstrate the breadth of its utility. Mipomersen, a second-generation antisense inhibitor of apoB-100, is the first drug to emerge from the Company's cardiovascular research program, which was established in 2000. Within three years, Isis scientists advanced this drug from early stages of drug discovery into Phase 1 development, and it is currently in Phase 3 development for FH patients with high cholesterol at high risk of cardiovascular disease. In addition, Isis researchers have rapidly explored more than 40 cardiovascular gene targets in vitro and evaluated antisense inhibition of many of these genes in animal models.   Most recently, Isis and Bristol-Myers Squibb identified an antisense development candidate that targets PCSK9.  PCSK9 helps regulate the amount of cholesterol in the bloodstream and could offer a new and complementary mechanism to current lipid-lowering therapies for the prevention and treatment of cardiovascular disease.

In addition to cardiovascular disease gene targets, Isis researchers have explored more than 120 targets in animal models as part of the Company’s metabolic drug discovery program.  From this initial work, the Company has selected and moved into development four distinct and complementary antisense drugs to treat metabolic disease.  The most recent antisense drug to emerge from the Company’s metabolic disease program is ISIS 388626, the Company’s first antisense drug developed toward SGLT2, a target in the kidney, which has demonstrated unusually high potency in early preclinical studies.

In addition to the Company’s exciting cardiovascular and metabolic disease franchises, Isis researchers continue to explore new opportunities for antisense drugs to treat a broad range of diseases including neurodegenerative and inflammatory diseases and cancer.