Isis Pharmaceuticals, Inc. is a genomics-based drug discovery and development company, focused exclusively on the untapped therapeutic target, RNA. Founded in 1989, the mission of Isis is to develop RNA-based technologies, such as antisense. Very little was known about antisense when the company was first established, but the founders envisioned an opportunity to revolutionize the pharmaceutical industry with a more efficient and targeted means of drug discovery. Since then, Isis scientists have made tremendous progress advancing the science of antisense, unveiling capabilities that have far exceeded our expectations.

The goal of antisense drugs is to intervene at the RNA level and prevent the production of proteins involved in disease. Antisense drugs are designed to complement and thus interact to a specific segment of messenger RNA (mRNA). A mechanism in the cell recognizes an antisense drug hybridized to mRNA and dispatches a natural cellular enzyme to destroy the mRNA. By destroying the mRNA, the disease-causing protein the mRNA codes for will not be produced. This is the first class of drugs targeted to control expression of genes through interactions with RNA. Antisense drugs are designed to interact very specifically to their intended mRNA target. This high degree of specificity can make antisense drugs more effective and less toxic than traditional drugs.

Beyond antisense, Isis scientists have created another technology that exploits their knowledge of RNA. Ibis Therapeutics™, a division of Isis, is discovering small molecule drugs that interact with RNA. The Ibis team is also designing a diagnostic tool to detect infectious organisms, including those that could be used in potential biological warfare attacks.

Isis is capitalizing on its expertise through the following business components:

Antisense drug discovery and development is the cornerstone of Isis. The company is the leader in all aspects of antisense technology advancement, including the development of new chemistries, novel formulations and innovative drugs.

We have a broad antisense pipeline with compounds in pre-clinical and all phases of clinical development to treat a wide variety of health conditions, including infectious, inflammatory and metabolic diseases and cancer.

Isis was granted U.S. marketing clearance for the world’s first antisense drug, Vitravene® (fomivirsen), in 1998. Vitravene is marketed worldwide by Novartis Ophthalmics.

In GeneTrove, our functional genomics division, scientists apply the selectivity and efficiency of antisense to determine the function of specific genes (gene functionalization) and their value as drug discovery targets (target validation). Pharmaceutical companies have access to this information through:

• Custom Target Validation Collaborations
• Intellectual Property Licensing Program

GeneTrove is a strategic component of Isis’ business, as it provides partners with access to antisense technology and a pathway to broaden into antisense drug discovery and development collaborations.

Ibis Therapeutics™ has developed technology to revolutionize the detection and treatment of infectious diseases. There are three major components to Ibis’ technology: RNA target identification, mass spectrometry-based high-throughput screening against certain structured regions of an RNA target, and the discovery of new chemical structures that bind to RNA.

Scientists have expanded the value of Ibis’ technology beyond drug discovery to a revolutionary diagnostic application. The division is engaged in the development of a sensor designed to detect infectious organisms, including known, unknown, unculturable or bioengineered elements that could be used in potential biological warfare attacks. The program is called the Triangulation Identification Genetic Evaluation of Risks (TIGER). Its development is underwritten by significant contracts from the Defense Advanced Research Projects Agency (DARPA).

With nearly 1,200 issued or licensed patents worldwide, Isis is the owner of the largest antisense and RNA patent estate in the pharmaceutical industry. We hold key patents covering antisense mechanisms, biology, chemistry and inhibitors of gene expression. Our patent estate is a valuable asset to the company and our shareholders, as it protects our inventions in RNA-based drug discovery and encourages revenue-generating partnerships.