Isis Initiates Phase 1 Study of ISIS-TTRRx and Earns $5 Million Milestone Payment From GlaxoSmithKline

CARLSBAD, Calif., May 19, 2011 /PRNewswire/ -- Isis Pharmaceuticals, Inc. (NASDAQ: ISIS) announced today that it has earned a $5 million milestone payment from GlaxoSmithKline (GSK) related to the initiation of a Phase 1 clinical study for ISIS-TTRRx.  ISIS-TTRRx is designed to treat transthyretin amyloidosis, a severe and rare genetic disease characterized by slow degeneration of peripheral nerve and/or heart tissues. ISIS-TTRRx is the first antisense drug to enter development under Isis' strategic alliance with GSK.

"We are very pleased with the successes of our collaboration with GSK, a partner with significant expertise in the development of drugs to treat severe and rare diseases.  In a little over a year, we have begun clinical development on the first drug in this collaboration, and we look forward to moving additional drugs from this collaboration into our pipeline," said B. Lynne Parshall, Chief Operating Officer and CFO of Isis.   "The progress we have made with GSK is representative of the value this type of alliance can provide to us and to our partners.  The innovative structure of this alliance allows us to control and facilitate rapid development of drugs while working together with a high-quality partner to maximize the value of the drugs in late-stage development and commercialization.  Already we have earned $48 million in payments from GSK, including $8 million this year.  This year, we anticipate making significant progress in our drugs to treat severe and rare diseases, such as transthyretin amyloidosis."

ISIS-TTRRx is an antisense drug that targets transthyretin, or TTR, for the treatment of transthyretin amyloidosis, a fatal disease that affects one in 100,000 people or about 50,000 people worldwide.  ISIS-TTRRx will initially be developed for patients with familial amyloid polyneuropathy, or FAP, who have TTR build up in their peripheral nerves and experience the loss of motor functions, such as walking.  Although these patients experience debilitating nerve damage throughout their body, they typically die from wasting due to the accumulation of TTR in the intestinal tract, which prevents the proper absorption of nutrients.  Currently there are no approved drugs to treat transthyretin amyloidosis, and the only approved available option is liver transplant.  Unfortunately, availability of donor livers is very limited and only a fraction of patients are eligible for this very expensive and invasive procedure.  

In March 2010, Isis entered into a strategic alliance with GSK to develop RNA therapeutics for rare and infectious diseases.  Under the terms of the agreement, Isis received an upfront $35 million payment from GSK and is eligible to receive license fees and milestone payments, totaling nearly $1.5 billion, in the event all six programs are successfully developed for one or more indications and commercialized through to pre-agreed sales targets.  With the initiation of the Phase 1 study of ISIS-TTRRx, Isis has earned $10 million in milestone payments under the collaboration.


Transthyretin amyloidosis is a genetic disease in which the patient inherits a mutant gene that produces a misfolded form of TTR, which progressively accumulates in tissues, impairing their function.  In patients with transthyretin amyloidosis, both the mutant and normal forms of TTR can build up as fibrils in tissues, including heart, peripheral nerves, and the gastrointestinal tract.  The presence of fibrils interferes with the normal functions of these tissues, and as the fibril deposits enlarge more tissue damage occurs and the disease worsens.  There are two common types of transthyretin amyloidosis, familial amyloid cardiomyopathy, or FAC, which affects more than 40,000 patients worldwide, and FAP, which affects more than 10,000 patients worldwide.  Patients with FAC have TTR build up in the heart muscle and succumb to heart failure five to six years after symptom onset.  Patients with FAP have TTR build up in peripheral nerve tissue leading to the loss of nerve function and wasting.  ISIS-TTRRx inhibits the production of all forms of TTR, offering a unique approach to treat all types of transthyretin-related amyloidosis.  


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 24 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 has designed and executed a patent strategy that has provided the Company with strong and extensive protection for Isis' drugs as well as all aspects of antisense drug discovery, development and manufacturing.  Additional information about Isis is available at


This press release includes forward-looking statements regarding Isis' collaboration with GlaxoSmithKline, the discovery, development and potential of drugs for severe and rare diseases, and the development, activity, therapeutic potential and safety of ISIS-TTRRx.  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 drugs.  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, 2010 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., its jointly owned subsidiary.

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

SOURCE Isis Pharmaceuticals, Inc.