Pipeline

Clinical | Preclinical

Therapeutic Area

Severe & Rare

Our severe and rare disease franchise is the largest franchise in our pipeline. We believe that our antisense technology could offer effective therapies for patients with severe and rare diseases and neurological disorders that are life-threatening or fatal and for which there are limited treatment options. According to the National Institutes of Health, or NIH, there are approximately 5,000 to 8,000 rare diseases, many life-threatening or fatal. Unfortunately, patients with many of these severe and rare diseases have few effective therapies available. Since most severe and rare diseases are genetic or have a genetic component, parents often pass the disease to their children, creating a legacy of the disease and resulting in profound effects on the family. IONIS-SMNRx, the most advanced neurological drug in our pipeline, is now in two Phase 3 studies for the treatment of infants and children with SMA.

We are discovering and developing antisense drugs to treat severe and rare and neurological diseases for which there is a need for new treatment options. We have established strategic alliances in drug development areas that are high risk or in which our partners have significant expertise and resources to allow us to expand our drug discovery and development efforts beyond what we would choose to do internally. For example, our strategic partnerships with Biogen Idec and Roche have supported advancing five drugs for the treatment of neuromuscular or neurological diseases in our pipeline.

Due to the severe nature of these diseases and the lack of available treatments, there is an opportunity for more flexible and efficient development paths to the market. This means that, in some cases, the studies necessary for us to demonstrate proof-of-concept with a particular drug may also be the studies that complete our marketing registration package, thereby providing us with a relatively rapid path to market for potential new treatments for devastating and often fatal diseases.

Drug
Target
Partner
Indication

IONIS-BIIB5Rx

Undisclosed

Biogen

Neurodegenerative Disease

IONIS-BIIB6Rx

Undisclosed

Biogen

Neurodegenerative Disease

IONIS-BIIB7Rx

Undisclosed

Biogen

Neurodegenerative Disease

IONIS-RHO-2.5Rx

RHO

-

Autosomal Dominant Retinitis Pigmentosa

IONIS-ENAC-2.5Rx

ENAC

--

Cystic Fibrosis

IONIS-TTR-LRx

TTR

-

TTR Amyloidosis

IONIS-DNM2-2.5Rx

DNM2

Dynacure

Centronuclear Myopathy

Cardiovascular

Cardiovascular disease is the leading cause of death in the United States. A common cause of cardiovascular disease is atherosclerosis, or premature plaque buildup, which occurs when cholesterol and inflammatory cells accumulate in blood vessels. Researchers have shown a strong correlation between high cholesterol levels and subsequent cardiovascular diseases. As such, lowering cholesterol is a key component in preventing and managing cardiovascular disease.

Cardiovascular disease is an area of focus for us. We have created a cardiovascular disease franchise comprised of drugs that target all the key components of cardiovascular disease, including various atherogenic lipids, inflammation and thrombosis, an aberrant blood clot formation responsible for most heart attacks and strokes. We have designed the majority of the drugs in our cardiovascular franchise to target cardiovascular risk factors. These drugs make up our lipid franchise and include IONIS-APO(a)Rx and IONIS-ANGPTL3Rx. Recent additions to our lipid franchise are our drugs that lower Lp(a) and angiopoietin-like 3 protein, or ANGPTL3. Lp(a) is another independent risk factor for cardiovascular disease. ANGPTL3 is a genetically validated target shown to play a significant role in regulating lipid levels. Humans who do not produce a functional ANGPTL3 protein due to a genetic mutation have extremely low levels of cholesterol, LDL-C, and very low levels of triglycerides and HDL-cholesterol. Currently available lipid-lowering therapies do not significantly lower apoC-III, triglycerides, Lp(a), or ANGPTL3. We believe that reducing levels of apoC-III, Lp(a) and ANGPTL3 could provide a complimentary approach to lipid-lowering therapies, including KYNAMRO(R). We are also developing follow-on LICA antisense drugs for the three drugs in our lipid franchise.

In order to maximize the value of our lipid franchise, while also maintaining control over the development and commercialization of these assets, we have created a wholly owned subsidiary, Akcea Therapeutics. Akcea is focused on the development and commercialization of our lipid franchise drugs and their follow on compounds.

In addition to our lipid franchise drugs, we have a promising anticoagulant agent, IONIS-FXIRx, in development in our cardiovascular disease franchise. We recently reported Phase 2 data on IONIS-FXIRx showing that IONIS-FXIRx-treated patients experienced a seven-fold lower incidence of venous thromboembolism and numerically fewer bleeding events compared to patients treated with enoxaparin, a commonly used anticoagulant. These data demonstrate that for the first time, an anticoagulant, IONIS-FXIRx, can prevent clotting without increasing bleeding, two biological events that were previously inseparable. Our latest drug to enter the franchise, IONIS-AGT-LRx, offers a novel approach to treating patients with high blood pressure.

Drug
Target
Partner
Indication

IONIS-AZ4-2.5-LRx

Undisclosed

AstraZeneca

Cardiovascular Disease

IONIS-FXI-LRx

FXI

Bayer

Clotting Disorders

Other

The broad applicability of our antisense technology allows us to create promising drugs and we have successfully developed novel drugs designed to treat many different diseases. In therapeutic areas that are outside of our core areas of development, we have licensed our drugs to highly focused satellite companies that have the specific expertise and resources to continue developing the drugs. Together with our partners we continue to advance drugs in clinical development that are outside of our core therapeutic areas, such as the ocular and antiviral drugs we and GSK are developing under our preferred partner collaboration.

Drug
Target
Partner
Indication

IONIS-JBI1-2.5Rx

Undisclosed

Janssen

GI Autoimmune Disease

IONIS-JBI2-2.5Rx

Undisclosed

Janssen

GI Autoimmune Disease