$ILNS working on age related macular degeneration!

$ILNS working on age related macular degeneration!! (AMD)

Age-related Macular Degeneration (AMD) is the leading cause of blindness in people over the age of 55.  There are two types of AMD; wet AMD is characterized by new blood vessel formation in the retina, and dry AMD is a precursor to the wet form of the condition.  Approximately 1.5 million people in the U.S. have wet AMD, and this number has been projected to nearly double by 2020.

The global market for wet AMD therapies currently is valued at US$ 4 billion annually, according to data from IMS Health.  This is a relatively new market that was introduced in the past decade with pegaptanib (Macugen®, OSI Pharmaceuticals), which was followed by the current market leader ranibizumab (Lucentis®; Genentech/Roche), an antibody fragment specific for vascular endothelial growth factor (VEGF).  While Lucentis accounts for approximately 98 percent of sales, a third therapy, Aflibercept (Eylea®; Regeneron Pharmaceuticals/sanofi-aventis), was launched in November 2011 that is generating significant attention.

While the numbers lead one to believe these drugs are curing the disease, a closer look reveals a very different story.  Only an estimated 30 percent of patients with wet AMD experience a significant improvement in vision with anti-VEGF therapy.  With 70 percent of wet AMD patients finding little benefit in visual improvement, alternative strategies are being investigated.

A promising new therapeutic approach arises from an understanding of the important similarities between AMD and Alzheimer’s disease, especially with respect to the role of beta amyloid (A?).  A? accumulates in the drusen (small off-white deposits that form either in the tissue layer underneath the retina or on the optic nerve head) and increasingly is believed to be a key regulator in the progression to AMD (see review by Ohno-Matsui, Progress in Retinal and Eye Research (2011) 217-238).   A? is thought to trigger AMD pathogenesis by several mechanisms:

• chronic inflammation including complement activation


• activation of microglial cells


• oxidative stress


• alteration of retinal epithelial (RPE) cells gene expression and phenotype

With varying degrees of success, A?-lowering and A?-neuroprotective strategies have demonstrated the ability to protect against damage in various models of retinal degeneration, including glaucoma and both wet and dry AMD.  For example, A? passive immunization strategies were shown in certain cases to reduce retinal damage and improve visual acuity in animal models of AMD.  Antioxidants, such as melatonin, have shown promise in this regard as well.

IN-N01-OX2: Intellect has a novel approach to combine passive immunotherapy with the antioxidant approach.  IN-N01-OX2 is an antibody-drug conjugate designed to

• prevent the buildup of A? in the eye


• prevent inflammation


• deliver melatonin, a potently neuroprotective molecule, to help reduce oxidative damage

IN-N01-OX2 is the first product being developed based on Intellect’s new CONJUMAB-A platform technology that it introduced in October 2011.  The Company believes IN-N02-OX2 is the first antibody-drug-conjugate being for an indication outside of oncology, where such molecules are used to deliver a toxic payload to kill cancer cells.  Intellect’s drug will be administered by injection into the eye, which is routinely performed in the treatment of AMD.

IN-N01-OX2 development is being led by Dan Shochat, Ph.D., Consulting Vice President Development, an internationally recognized leader in the development of antibody products.  Dr. Shochat led the development of Bexxar®, a radioiodinated antibody for the treatment of Non-Hodgkin's Lymphoma, which was approved by the FDA in June 2003.  At American Cyanamide Co. and in collaboration with Celltech, Dr. Shochat led the development of the first approved antibody-drug conjugate, Mylotarg®.  He also invented the technology and single-vial formulation and then developed the FDA-approved in vivo tumor-imaging reagent CEA-Scan®.  With Dr. Shochat’s expert assistance, Intellect has developed a detailed road-map for IN-N01-OX2 development to lead to the first clinical trials being initiated by the end of 2014.