Isis Pharmaceuticals, Inc. announced that it has added two new drugs to its development pipeline, ISIS-FGFR4Rx and ISIS-STAT3Rx.

ISIS-FGFR4Rx is designed to treat obesity by increasing metabolism, particularly by increasing lipid and fat burning. ISIS-FGFR4Rx specifically blocks the production of Fibroblast Growth Factor Receptor 4 (FGFR4) in the liver and fat tissue. In addition, ISIS-FGFR4Rx should not reduce FGFR4 expression in the Central Nervous System (CNS) or heart, thereby avoiding the CNS and cardiovascular side effects associated with many obesity drugs in development.

In preclinical studies, inhibition of FGFR4 lowered body weight and enhanced weight loss when administered as a single agent, in combination with a caloric-restricted diet and in combination with an appetite-suppressing drug and a caloric-restricted diet. The reduction in body weight was accompanied by an improvement in insulin sensitivity. ISIS-FGFR4Rx was safe and well tolerated in multiple species. ISIS-FGFR4Rx is the first drug in Isis' metabolic franchise to treat obesity.

“Obesity has become an epidemic. It is a condition that increases the risk of diabetes, heart disease, stroke, arthritis and some cancers, and an area where most centrally acting drugs have failed due to side-effects. Consequently, our peripherally acting drugs such as ISIS-FGFR4Rx could have significant therapeutic benefit without the associated central nervous system toxicities that plague many other anti-obesity drugs. Our ability to selectively target FGFR4 in only the tissues where FGFR4 plays an important role in modulating body weight makes it an ideal target for our anti-sense technology,” said Sanjay Bhanot, M.D., PhD, vice president, Metabolic Disorders and Head of Translational Medicine at Isis Pharmaceuticals. “In our preclinical studies, we observed reductions in body fat, reversal of existing obesity and improved insulin sensitivity with ISIS-FGFR4Rx, making this a promising drug with an exciting therapeutic profile.”

ISIS-STAT3Rx is designed to treat cancer by inhibiting the production of a gene critical for tumour cell growth and survival. Signal Transducer and Activator of Transcription 3 (STAT3) is over-active in a variety of cancers, including brain, lung, breast, bone, liver and multiple myeloma and promotes tumour cell growth and prevents cell death. In preclinical studies, ISIS-STAT3Rx demonstrated anti-tumour activity in animal models of human cancer with an attractive safety profile. ISIS-STAT3Rx will be evaluated in a variety of cancers where STAT3 is believed to play a key role such as liver cancers and multiple myeloma.

“Cancer is a therapeutic area in which we believe anti-sense drugs could have a profound treatment impact. STAT3 is a target that is widely viewed as promising, but it is inaccessible to traditional drug approaches due to the nature of the protein and its function in the cell,” said Brett P. Monia, PhD, vice president, Drug Discovery and Corporate Development. “ISIS-STAT3Rx adds to our already broad and mature cancer franchise consisting of a phase III drug and three phase II drugs, each with promising clinical data. These drugs inhibit many of the processes that tumour cells use to grow, proliferate, and metastasize."

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 anti-sense drug and has 24 drugs in development. Isis' drug development programs are focused on treating cardiovascular, metabolic, and severe neurodegenerative diseases and cancer. Isis' partners are developing anti-sense 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.