Macular Degeneration and Geographic Atrophy (a late stage of AMD) are characterized by a loss of central vision. Typically a dark spot(s) form in the central vision. Colors are less vivid and overall vision less sharp. Vision in low light is particularly difficult. Patients with AMD / GA experience difficulty recognizing faces and the routine tasks of every day life such as reading, writing, cooking etc. become a significant challenge. Patients with AMD / GA also experience an increased incidence of falls and other physical injuries as a consequence of their diminished vision.
The underlying disease mechanism is controversial, however, it is characterized by the accumulation of a fatty substance known as drusen and the ‘thinning” of retinal layers with loss of retinal cells including photoreceptors and pigmented epithelium.
There are two forms of Macular Degeneration "Dry" AMD and "Wet" AMD. Approximately 90% of patients have Dry AMD. Wet AMD can be treated with a class of drugs known as VEGF inhibitors. There are currently no approved therapeutics for Dry Macular Degeneration or the advanced stage of the disease known as Geographic Atrophy (GA).
A large and growing number of people are effected by AMD / Geographic Atrophy
There are more than 11 million individuals in the United States (US) and > 196 million worldwide living with some degree of AMD. Worldwide there are 5 million people living with GA and almost everyone with AMD will develop GA over time. (1)
Our strategy is based on restoring the expression of a gene necessary for the biosynthesis of long chain polyunsaturated fatty acids (LC-PUFA) which are critical for retinal function. During aging the gene becomes "silenced" by a process known as methylation. Our therapeutic programs target: 1) rescue of gene function using a de-methylating therapeutic and 2) gene therapy.
Our development approach leverages our expertise identifying the fastest path to market to meet the current medical need, with a follow-on program offering the curative potential of gene therapy.
Out fast-to-market approach is based on developing an intra-vitreal formulation of decitabine, a de-methylating agent currently approved for certain cancers. Decitabine is highly effective at reactivating genes silenced by methylation. It works by depleting cells of DNA Methyl Transferase 1 without which cells are unable to maintain DNA methylation.
Our gene therapy strategy is based on increasing target gene expression using a viral vector carrying the target gene or an mRNA based therapeutic.