Topical Eyedrops Increasing Lysyl Oxidase and Dopamine Activity to Control Myopia

Iveena Delivery Systems, Inc., Salt Lake City UT

Investigators

Abstract

Project Summary Pediatric myopia is affecting approximately one-third of children and adolescents 1, and is increasing globally at an alarming rate with significant increases in pathologic conditions associated with high myopia including retinal detachment, maculopathy, cataract and glaucoma. It is the leading cause of vision impairment in the world. A recent report from the National Academies of Science, Engineering, and Medicine recommends classifying myopia as an official disease that requires a medical diagnosis 2. Currently, there are no FDA-approved pharmacologic therapies to slow the progression of myopia. We propose a novel topical eyedrop, IVMED-85 for treating myopia. It is a first-in-class medication delivering copper to upregulate lysyl oxidase (a cuproenzyme the activity of which is deficient in myopic sclera) to pharmacologically induce scleral and corneal crosslinking, and biomechanical strengthening of both tissues. In our phase 1 project, we demonstrated the efficacy of our eyedrops in juvenile myopic guinea pigs, by slowing axial lengthening and reducing myopia progression compared to control. We also demonstrated stability of formulation for 12 months in long-term and 6 months accelerated conditions according to ICH guidelines. With internal funding, we have completed two GLP toxicology studies in juvenile species according to our pre-IND meeting with the FDA. In this phase 2 project, we propose 3 specific aims that will enable us to submit an IND with a well thought clinical protocol to start US clinical trials. First, we will confirm biochemical effects of our eyedrop on a key biomarker of crosslinking, and determine if the effect of therapy is durable after cessation of treatment, or if there is a rebound myopic progression. Second, we will confirm if our copper eyedrops increase retinal dopamine synthesis through up-regulation of the importance of copper in dopamine synthesis in retina cells, which could improve choroidal thickness and reduce scleral hypoxia. This mechanistic data will add further patent protection to IVMED-85 and will enhance competitive additional advantage over other potential treatments. Third, we will complete GMP manufacturing for clinical trials and assess long-term stability of the eyedrop.