Isis Pharmaceuticals Adds Two New Drugs to Development Pipeline

ISIS-FXIRx to Treat Clotting Disorders

ISIS-SMNRx to Treat Spinal Muscular Atrophy

R&D Webcast, December 3rd, 11:30 a.m. EST at

Isis to Present Additional Details on Both Programs

Dec 03, 2009, 08:00 ET from Isis Pharmaceuticals, Inc.

CARLSBAD, Calif., Dec. 3 /PRNewswire-FirstCall/ -- 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."


Splicing is a normal mechanism that the cell uses in order to produce many different, but closely related proteins from a single gene by varying the processing of the RNA. It is estimated that of the approximately 25,000 genes in the human genome, 40% to 60% have alternative splice forms. In some cases, alternative splicing of proteins results in the production of proteins that are involved in disease. These diseases are referred to as splicing diseases and include SMA, cystic fibrosis and Duchenne's muscular dystrophy.


At 11:30 a.m. Eastern Time today, December 3, Isis will conduct a live webcast presentation of its Research & Development Day. Interested parties may access the webcast at A replay of the webcast will be available on Isis' Web site for a limited time.


Isis is exploiting its expertise in RNA to discover and develop novel drugs for its product pipeline and for its partners. The Company has successfully commercialized the world's first antisense drug and has 21 drugs in development. Isis' drug development programs are focused on treating cardiovascular, metabolic and severe neurodegenerative diseases and cancer. Isis' partners are developing antisense drugs invented by Isis to treat a wide variety of diseases. Isis and Alnylam Pharmaceuticals are joint owners of Regulus Therapeutics Inc., a company focused on the discovery, development and commercialization of microRNA therapeutics. Isis also has made significant innovations beyond human therapeutics resulting in products that other companies, including Abbott, are commercializing. As an innovator in RNA-based drug discovery and development, Isis is the owner or exclusive licensee of over 1,600 issued patents worldwide. Additional information about Isis is available at

This press release includes forward-looking statements regarding the development, activity, therapeutic potential and safety of ISIS-FXIRx in the treatment of clotting and bleeding disorders and ISIS-SMNRx in the treatment of SMA. Any statement describing Isis' goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such products. Isis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Isis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Isis. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Isis' programs are described in additional detail in Isis' annual report on Form 10-K for the year ended December 31, 2008, and its most recent quarterly report on Form 10-Q, which are on file with the SEC. Copies of these and other documents are available from the Company.

In this press release, unless the context requires otherwise, "Isis," "Company," "we," "our," and "us" refers to Isis Pharmaceuticals and its subsidiaries, including Regulus Therapeutics Inc.

Isis Pharmaceuticals is a registered trademark of Isis Pharmaceuticals, Inc. Regulus Therapeutics is a trademark of Regulus Therapeutics Inc.

SOURCE Isis Pharmaceuticals, Inc.