iCo-007 (formerly known as ISIS 13650) is a second generation antisense compound being developed by iCo for the treatment of various eye diseases caused by the formation of new blood vessels (angiogenesis) such as age-related macular degeneration (AMD) and diabetic retinopathy (DR).

Ocular angiogenesis, the formation of new blood vessels in the eye, appears to be controlled by multiple growth factors including vascular endothelial growth factor (VEGF) and can lead to the obstruction of vision. iCo-007 is an antisense inhibitor of c-Raf kinase, an enzyme important in the signal transduction pathway triggered by VEGF as well as other important growth factors.  In preclinical studies, antisense inhibition of c-Raf kinase was associated with a reduction in the formation of new blood vessels in the eye, suggesting c-Raf kinase inhibition could be valuable in the treatment of both AMD and diabetic retinopathy.

iCo 007 is a second generation antisense compound, which means it has increased target binding affinity and resistance to degradation.  Increased affinity increases potency allowing for more activity at lower doses which in turn can reduce the overall cost of therapy.  Slower clearance of the drug from the body through reduced degradation should allow for less frequent dosing and better patient compliance and convenience.  Intravitreal injection of second generation antisense compounds have also been found to be well tolerated.

iCo plans to file an Investigational New Drug (IND) application with the US Food and Drug Administration (FDA) in 2006.

Age-related Macular Degeneration & Diabetic Retinopathy

Age-related Macular Degeneration (AMD) is a degenerative condition of the macula or central part of the retina.  The wet form of AMD occurs when new vessels form to improve blood supply to oxygen-deprived retinal tissue.  These new vessels however are often abnormal and more prone to breakage and leakage.  The wet form of AMD, accounts for only 10-15% of all cases of AMD, but is responsible for 90% of the severe vision loss associated with the disease and is the leading cause of blindness in people over the age of 50.  According to research by the National Eye Institute, approximately 1.7 million Americans are affected by the disease and roughly 200,000 new cases of AMD are diagnosed every year in the United States.  As a disease of the elderly, the incidence is expected to grow with the aging of the population.  Existing treatments for AMD, worth over half a billion dollars (USD), have shown limited long-term success and often require frequent intervention.  The AMD market is projected to grow to US$1.6B by 2008.

Diabetic retinopathy (DR) is a complication of diabetes that leads to progressive damage to the small blood vessels of the eye.  The condition affects an estimated 5.6 million Americans and is the leading cause of blindness in adults of working age (20-74) in industrialized countries (Decision Resources, Inc.).  According to the American Diabetes Association, in the U.S., diabetes is responsible for 8% of legal blindness and each year, between 12,000 to 24,000 people lose their sight because of diabetes.  At present there are no therapeutic drugs approved for the treatment of diabetic retinopathy.