ISIS-FXIRx and ISIS-SMNRx included in Isis Pharmaceuticals' development pipeline

Isis Pharmaceuticals, Inc. (Nasdaq: ISIS) announced today that it has added two new drugs to its development pipeline, ISIS-FXIRx and ISIS-SMNRx.

ISIS-FXIRx is designed to treat clotting disorders without increased risk of bleeding. High levels of Factor XI are linked to myocardial infarction, stroke and venous thrombosis. In preclinical studies, ISIS-FXIRx has demonstrated potent antithrombotic activity and a superior safety profile (lower risk of bleeding) compared with standard anti-clotting agents, including low molecular weight heparin, warfarin and Factor Xa inhibitors. Isis is developing ISIS-FXIRx as part of its strategy to discover and develop antisense drugs against a range of liver-derived coagulation factors for the treatment of thromboembolic, inflammatory and oncology-related diseases. Isis' scientist, Robert MacLeod, Ph.D., and collaborators will be presenting data on ISIS-FXIRx in a poster titled "Pharmacological Characterization and Structure Activity Relationship of FXI Antisense Oligonucleotides in Cynomolgus Monkeys" at the upcoming American Society of Hematology meeting on Sunday, December 6.

"Using our efficient antisense drug discovery platform, we were able to selectively target and inhibit the production of every clotting factor produced in the liver. This extensive screening effort allowed us to evaluate the relative profiles of inhibitors of each clotting factor and to select ISIS-FXIRx, which we believe will provide the optimal therapeutic activity without causing bleeding, a major side effect of marketed anti-clotting drugs," said Stanley T. Crooke, M.D., Ph.D., Chairman and Chief Executive Officer of Isis. "With ISIS-FXIRx entering development, we are continuing to broaden our cardiovascular franchise beyond regulation of lipids and inflammatory processes into thrombosis."

ISIS-SMNRx is designed to treat spinal muscular atrophy (SMA), a neuromuscular disorder and the leading genetic cause of infant mortality. The incidence of the disease is 1 in 6,000-10,000 births, and most infants born with severe SMA die within 2 years according to the National Institutes of Health's National Institute of Neurological Disorders and Stroke. Isis is developing ISIS-SMNRx as part of its strategy to discover and develop antisense drugs against neurodegenerative diseases. ISIS' SMA program is part of its collaboration in neurodegenerative disease with Genzyme, pursuant to which Genzyme has an exclusive option to license ISIS-SMNRx from ISIS.

SMA is caused by a genetic deletion of the survival motor neuron 1 (SMN1) gene. ISIS-SMNRx is designed to treat SMA by modulating the splicing of a closely related pre-mRNA (SMN2), which leads to the production of the protein, survival motor neuron (SMN), which is associated with normal motor function. By altering splicing to produce SMN, ISIS-SMNRx may be able to compensate for the underlying genetic defect. ISIS-SMNRx is the first antisense drug to enter Isis' development pipeline that modulates splicing, a novel antisense mechanism.

"With ISIS-SMNRx we have broadened the application of our technology beyond an RNase H based mechanism that inhibits the production of a disease-causing protein to an RNA splicing based mechanism that increases the production of a protein important for normal function," continued Dr. Crooke. "There are a large number of serious diseases that are associated with splicing disorders. The ability of antisense drugs to specifically target the RNA that drives splicing makes our antisense splicing drugs uniquely suited to correct aberrant splicing caused by genetic disease and to provide a therapy for these previously untreatable diseases. This significant advance expands the application of our drug discovery technology to help patients with these severe splicing disorders."