Macular edema (ME) is a common disease secondary to retinal vein occlusion and both Type I and Type 2 Diabetes. It is the leading cause of blindness in people between the ages of 20-74. Lucentis and Eylea have been approved for the treatment of ME. Although effective, they do not increase the visual acuity for about half the patients suffering from ME. We have developed ACX107, a 20-mer peptide with remarkable activity against a host of pro-angiogenic growth factors, which we believe will improve vision more effectively and in more patients because of its broad anti-angiogenic activity. We have found that ACX107 inhibits choroidal neovascularization, retinal neovascularization, causes neovascular regression, inhibits retinal detachment, and dramatically inhibits VEGF induced vascular leakage in mouse and rabbit models. Remarkably the peptide appears to work even 1 month after a single intravitreal injection. These results suggest that ACX107 could be the next generation drug for the treatment of ME. Here we propose to complete a dose ranging study as well as a duration of activity study, to develop an analytical method to quantify ACX107, and do IND enabling toxicology studies. What we have proposed here is the portion of the full development work that we can accomplish on the budget and time confines of the Phase I SBIR mechanism. The rest of the development work will require significantly more funding which we could accomplish with a Phase II SBIR or other investment like that of a strategic partnership.
Public Health Relevance Statement: Public Health Relevance: There is a large medical need for drugs for the treatment of macular edema. We have identified a promising peptide therapeutic that has shown remarkable activity in animal models of the human disease. Here we propose studies to identify the optimal dose and the duration of effect as well as work to develop an analytical method for quantifying the peptide in ocular fluids and serum. Using this method we will quantify the amount of the peptide in various parts of the rabbit eye after dosing.
NIH Spending Category: Biotechnology; Diabetes; Eye Disease and Disorders of Vision; Macular Degeneration; Neurodegenerative
Project Terms: Age; analytical method; angiogenesis; Angiogenic Factor; Animal Model; Antibodies; aqueous; Aqueous Humor; Blindness; Blood; Blood Vessels; Budgets; Choroidal Neovascularization; Development; Disease; Dose; Drug or chemical Tissue Distribution; Enzyme-Linked Immunosorbent Assay; Extravasation; Eye; Funding; Growth Factor; human disease; Hypoxia; improved; intravitreal injection; Investments; Liquid substance; Lucentis; macular edema; Medical; Methods; mimetics; Modeling; Mus; neovascular; next generation; Non-Insulin-Dependent Diabetes Mellitus; Oryctolagus cuniculus; Patients; Peptides; Permeability; Pharmaceutical Preparations; Phase; Pigments; public health relevance; Rest; Retinal Detachment; Retinal Neovascularization; Retinal Vein Occlusion; Secondary to; Serum; Small Business Innovation Research Grant; Testing; Therapeutic; Time; Toxicology; Up-Regulation (Physiology); Vascular Endothelial Growth Factors; Vision; Visual Acuity; Vitreous humor; Work
