Profile: Isis Pharmaceuticals, Inc. (ISIS.O)

Isis Pharmaceuticals, Inc. (Isis), incorporated in January 10, 1989, is engaged in antisense technology, exploiting a drug discovery platform to create a pipeline of drugs. The Company operates in a two principal segments: Drug Discovery and Development and Regulus Therapeutics Inc. Within the Drug Discovery and Development segment, its drug discovery platform enables the Company to identify drugs, providing potential targets to treat a range of diseases. As of December 31, 2008, the Company has 19 drugs in development. Its partners are licensed to develop, with the Company’s support, 15 of these 19 drugs. The Company and Alnylam established Regulus Therapeutics Inc. as a company focused on the discovery, development and commercialization of microRNA therapeutics. In January 2009, the Company sold its subsidiary, Ibis Biosciences, Inc. to Abbott Molecular Inc. (AMI), a wholly owned subsidiary of Abbott Laboratories.

Mipomersen

Mipomersen reduces the production of apolipoprotein B-100 (apoB-100), which is the protein that carries certain forms of cholesterol and triglyceride particles in the bloodstream. Cholesterol can be carried in the bloodstream in a variety of forms, with high-density lipoprotein (HDL), being the good form, and low-density lipoproteins (LDL) and very low-density lipoproteins (VLDL) being the bad or atherogenic forms directly involved in heart disease. ApoB-100 is found in both bad types of cholesterol particles.

ISIS-CRP

ISIS-CRP is a generation 2.2 antisense drug that inhibits CRP, a protein produced in the liver. CRP levels increase during inflammatory disorders, and excessive amounts of CRP have been linked to coronary artery disease. Furthermore, a growing body of evidence from clinical trials implicates CRP in cardiovascular disease progression.

BMS-PCSK9

BMS-PCSK9 is an antisense drug that targets proprotein convertase subtilisin/kexin type 9 (PCSK9), a member of a large family of proteins. PCSK9 is a protein involved in the metabolism of cholesterol. BMS-PCSK9Rx can offer a new mechanism to current lipid-lowering therapies for the prevention and treatment of cardiovascular diseases.

ISIS 113715

ISIS 113715 is an antisense inhibitor of protein tyrosine phosphatase 1B (PTP-1B), for the treatment of type 2 diabetes. PTP-1B is responsible for turning off the activated insulin receptor. ISIS 113715 is in Phase II development for the treatment of type 2 diabetes.

ISIS-SGLT2

ISIS-SGLT2 is a generation 2.2 antisense drug targeting sodium glucose co-transporter type 2 (SGLT2), which is a transporter for blood sugar re-absorption in the kidney. By specifically blocking the production of SGLT2 in the kidney tissue, it can promote blood sugar excretion and reduce blood sugar levels, without having any effect on a related gene product, SGLT1.

OGX-011

OGX-011 is a second generation antisense inhibitor of clusterin, a secreted protein that acts as a cell-survival protein and is over-expressed in response to anti-cancer agents, like chemotherapy, hormone ablation and radiation therapy. The Company and OncoGenex jointly discovered and conducted the initial development of OGX-011.

OGX-427

OGX-427 is the second anti-cancer drug in its collaboration with OncoGenex. OGX-427 is a second generation antisense inhibitor targeting heat shock protein 27 (Hsp27).

LY2275796

LY2275796 is the second antisense anti-cancer drug and is in Phase I development. This drug targets eukaryotic initiation factor-4E (eIF-4E), a protein involved in tumor progression, angiogenesis and metastases, including breast, head and neck, prostate, lung, bladder, colon, thyroid and non-Hodgkin’s lymphomas.

ACHN-490

ACHN-490 is a neoglycoside, which is an aminoglycoside drug that Achaogen is developing for the treatment of multi-drug resistant gram-negative bacterial infections. ACHN-490 displays spectrum activity against multi-drug-resistant gram-negative bacteria that cause systemic infections, including E. coli and methicillin-resistant staphylococcus aureus.

AIR645

AIR645 is an inhaled second generation antisense inhibitor of the alpha subunit of the interleukin 4 receptor (IL-4R-alpha), which inhibits interleukin 4 (IL-4) and interleukin 13 (IL-13) signaling. IL-4 and IL-13 are two cytokines in asthma, which regulate inflammation, mucus overproduction and airway hyper-responsiveness.

ATL1103

ATL1103 is an antisense drug that inhibits growth hormone receptor (GHr), which is a receptor that reduces the level of circulating insulin-like growth factor-1 (IGF-1), produced in the liver. IGF-1 is a hormone that contributes to various diseases, including acromegaly, which is characterized by abnormal growth of organs, face, hands and feet, as well as for diabetic retinopathy, a common disease of the eye and a leading cause of blindness.

iCo-007

iCo-007 is an antisense inhibitor of c-Raf kinase. In pre-clinical studies, antisense inhibition of c-Raf kinase was associated with a reduction in the formation and leakage of new blood vessels in the eye, suggesting inhibiting c-Raf kinase can improve treatment for both diabetic macular edema and diabetic retinopathy.