Profile: Isis Pharmaceuticals Inc (ISIS.PH)

ISIS.PH on Philadelphia Stock Exchange

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21 Nov 2014
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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. As of December 31, 2011, the Company operates in the Drug Discovery and Development operations segments. The Drug Discovery and Development operations help the Company to identify drugs, providing a wealth of potential targets to treat a range of diseases. As of December 31, 2011, the Company had two generation 2.5 drugs in development, ISIS-STAT3Rx and ISIS-FVIIRx. During the year ended December 31, 2011, the Company had 26 drugs in development. Its partners are licensed to develop, with the Company’s support, 10 of these 26 drugs. As of December 31, 2011, the Company owns 20% interests in Santaris Pharma A/S, Achaogen Inc., and Atlantic Pharmaceuticals Limited, which are privately-held, and Antisense Therapeutics Limitet (ATL), and iCo Therapeutics Inc., which are publicly utilities.

KYNAMRO (mipomersen sodium)

The Company and Genzyme Corporation are developing KYNAMRO to treat patients with severe forms of familial hypercholesterolemia (FH), at high cardiovascular risk and who cannot reduce their low-density lipoprotein cholesterol (LDL-C). KYNAMRO is a apolipoprotein-B (apo-B) synthesis inhibitor in development for the reduction of LDL-C. KYNAMRO acts by decreasing the production of apolipoprotein-B, or apo-B. Apo-B provides the structural core for atherogenic lipids, including LDL-C, which carries cholesterol through the bloodstream. KYNAMRO reduces LDL-C and other key atherogenic lipids linked to cardiovascular disease by preventing their formation.

ISIS-CRPRx

ISIS-CRPRx is an antisense drug that targets CRP, a protein produced in the liver. CRP levels increase during inflammatory disorders, and scientists have linked excessive amounts of CRP to coronary artery disease. The Company evaluated ISIS-CRP in a Phase II rheumatoid arthritis.

ISIS-APOCIIIRx

ISIS-APOCIIIRx is an antisense drug designed to reduce apolipoprotein C-III (apoC-III) protein production and lower triglycerides. ApoC-III is responsible for triglyceride transport in the blood and is a pro-inflammatory protein and an independent cardiovascular risk factor. The Company, as of December 31, 2011, has completed Phase I study of apoC-III.

ISIS-FXIRx

ISIS-FXIRx is an antisense drug designed to treat clotting disorders. It targets Factor XI, a clotting factor produced in the liver. The Company has completed Phase I study of ISIS-FXIRx.

ISIS-APOARx

ISIS-APOARx is an antisense drug designed to reduce apolipoprotein(a) in the liver to offer a direct approach for reducing lowering lipoprotein a (Lp(a)). Lp(a) is an independent risk factor for cardiovascular disease.

ISIS-FVIIRx

ISIS-FVIIRx is an antisense drug designed to reduce Factor VII. Factor VII is a key component of the tissue factor coagulation pathway, for the treatment or prevention of thrombotic diseases.

ISIS-FGFR4Rx

ISIS-FGFR4Rx is an antisense drug that reduces the production of fibroblast growth factor receptor 4 (FGFR4), in the liver and fat tissues, which decreases the body’s ability to store fat while increasing fat burning and energy expenditure. The Company is evaluating ISIS-FGFR4Rx in a Phase I study.

ISIS-GCCRRx

ISIS-GCCRRx is an antisense drug that targets the glucocorticoid receptor (GCCR). Glucocorticoid hormones affect a variety of processes throughout the body, including promoting liver glucose production and fat storage. The Company is evaluating ISIS-GCCRRx in a Phase I study.

ISIS-GCGRRx

ISIS-GCGRRx is an antisense drug that targets the glucagon receptor (GCGR) to reduce the effects of glucagon. In addition, reducing GCGR produces more active glucagon-like peptide (GLP-1) a hormone that preserves pancreatic function and enhances insulin secretion. The Company is evaluating ISIS-GCGRRx in a Phase I study.

ISIS-PTP1BRx

ISIS-PTP1BRx is an antisense drug that targets protein tyrosine phosphatase-1B (PTP-1B) to treat type two diabetes. The Company designed ISIS-PTP1BRx to increase the body’s sensitivity to the natural hormone insulin, resulting in better glucose control for patients with type two diabetes. The Company is evaluating ISIS-PTP1BRx in a Phase I study.

ISIS-DGAT2Rx

ISIS-DGAT2Rx is an antisense drug that specifically reduces the production of diacylglycerol acyltransferase-2 (DGAT-2), a key component in the synthesis of triglycerides. By reducing DGAT2, ISIS-DGAT2Rx should reduce liver fat in patients with NASH, a common and often asymptomatic liver disease that can cause irreversible damage to the liver, and lead to liver cirrhosis and cancer.

OGX-011

OGX-011, as of December 31, 2011, is under license to Teva Pharmaceutical Industries Ltd. (Teva) is a second-generation antisense drug that targets clusterin, a secreted protein that acts as a cell-survival protein and is over-expressed in response to anti-cancer agents. OncoGenex evaluated OGX-011 in five Phase II studies in combination with various cancer therapies for prostate cancer, non-small cell lung cancer (NSCLC) and breast cancer. OncoGenex has also evaluated OGX-011 in a Phase I/II combination study in patients with NSCLC.

ISIS-EIF4ERx

ISIS-EIF4ERx targets the gene that is responsible for producing the protein eukaryotic initiation factor-4e (eIF-4E), which cells over-express in a variety of cancers, including prostate, lung, ovarian, liver, breast, head and neck, bladder, colon, thyroid and lymphoma. Eli Lilly and Company completed a Phase I study of ISIS-EIF4ERx. Eli Lilly and Company has rights to license ISIS-EIF4ERx from he Company on predefined terms.

LY2181308

LY2181308 is an antisense drug that targets survivin, which plays a role in cancer cell death and is one of the commonly over expressed proteins in cancers. The Company licensed its anti-cancer drug, LY2181308, to Eli Lilly and Company as part of the Company’s antisense drug discovery research collaboration in cancer. Eli Lilly and Company is evaluating LY2181308 as a combination therapy in two separate randomized Phase II studies.

OGX-427

OGX-427 is a second-generation antisense drug targeting heat shock protein 27 (Hsp27), which is a cell survival protein that cells over produce in response to many cancer treatments, including hormone ablation therapy, chemotherapy and radiation therapy. OncoGenex is evaluating OGX-427.

ISIS-STAT3Rx

The Company designed ISIS-STAT3Rx to treat cancer by inhibiting the production of a gene critical for tumor 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 tumor cell growth and prevents cell death.

ATL1103

ATL1103 is an antisense drug that targets the growth hormone receptor (GHr) a receptor that, when inhibited, 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, an abnormal growth disorder of organs, face, hands and feet, as well as diabetic retinopathy, a common disease of the eye and a cause of blindness, diabetic nephropathy of the kidney and certain forms of cancer.

ISIS-SMNRx

ISIS-SMNRx is an antisense drug designed to treat spinal muscular atrophy (SMA) a severe motor-neuron disease that is the genetic cause of infant mortality. The Company designed ISIS-SMNRx to potentially treat all types of childhood SMA by altering the splicing of a closely related gene, SMN2 that leads to the increased production of fully functional SMN protein. In January 2012, the Company and Biogen Idec entered into a partnership alliance that provides Biogen Idec an option to develop and commercialize ISIS-SMNRx.

ISIS-SOD1Rx

ISIS-SOD1Rx is an antisense drug that targets superoxide dismutase (SOD1). SOD1 is a protein associated with an inherited, aggressive form of amyotrophic lateral sclerosis (ALS).

ISIS-TTRRx

ISIS-TTRRx is an antisense drug designed to treat transthyretin amyloidosis (TTR amyloidosis) a severe and rare genetic disease in which the patient inherits a mutant gene that produces a misfolded form of TTR, which progressively accumulates in tissues. There are two common types of TTR amyloidosis, familial amyloid cardiomyopathy (FAC) and familial amyloid polyneuropathy (FAP). The Company completed Phase I evaluation study of ISIS-TTRRx.

ISIS-AATRx

ISIS-AATRx is an antisense drug that reduces production of alpha-1 antitrypsin (AAT) for the treatment of liver disease in patients with alpha-1 antitrypsin deficiency (AATD). AATD is a genetic disease in which the patient does not produce normal AAT, a protein primarily produced in the liver that protects lung tissue from damage.

Alicaforsen

Under license to Atlantic Pharmaceuticals Limited, alicaforsen is an antisense drug that targets intercellular adhesion molecule 1 (ICAM-1). ICAM-1 is over-expressed in a wide variety of inflammatory disorders, including ulcerative colitis and pouchitis. The Company has licensed alicaforsen to Atlantic Pharmaceuticals for pouchitis, UC and other inflammatory diseases.

ATL1102

ATL1102 is an antisense drug that ATL is developing for the treatment of multiple sclerosis (MS). ATL1102 inhibits CD49d, a subunit of very late antigen-4 (VLA-4).

EXC 001

EXC 001 is an antisense drug that targets connective tissue growth factor (CTGF) a growth factor that is over-expressed in damaged skin or tissue following a traumatic event. The Company co-discovered EXC 001 and licensed it to Excaliard for the local treatment of fibrotic diseases, including scarring. In November 2011, Pfizer Inc. acquired Excaliard and plans to continue to develop EXC 001. The Company has completed three Phase II studies of EXC 001.

iCo-007

iCo-007 is an antisense drug that targets c-Raf kinase. The Company discovered iCo-007 and licensed it to iCo Therapeutics Inc. (iCo) for the treatment of various eye diseases that occur as complications of diabetes. In August 2011, iCo initiated a Phase II study on iCo-007 in patients with diabetic macular edema.

Plazomicin

Plazomicin, formerly ACHN-490, is a aminoglycoside drug that Achaogen, Inc. is developing for the treatment of multi-drug resistant gram-negative bacterial infections. Achaogen has completed a Phase I study of plazomicin.

RNAi

RNAi is an antisense mechanism that uses small interfering RNA (siRNA) to target mRNA sequences. The Company has licensed RNAi to Alnylam Pharmaceuticals, Inc. (Alnylam).

Splicing

Splicing is a normal cellular mechanism that the cell uses to produce many different, but closely related proteins from a single gene by varying the processing of the RNA. The Company designs antisense drugs to control splicing to make one protein versus another. In December 2011, the Company initiated the study to utilize an alternative splicing mechanism.

MicroRNAs

MicroRNAs are small, RNA molecules, typically 20 to 25 nucleotides in length, which do not encode proteins but instead work as natural antisense sequences that scientists believe regulate the expression of approximately one-third of all human genes. The Company and Alnylam established Regulus Therapeutics Inc. as a company focused on the discovery, development and commercialization of microRNA therapeutics.

Company Address

Isis Pharmaceuticals Inc

2855 Gazelle Court
CARLSBAD   CA   92010
P: +1760.9319200
F: +1302.6555049

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