Targeted Intraceptor Nanoparticle for Macular Degeneration

DESCRIPTION provided by applicant Age related macular degeneration AMD is a leading cause of blindness in United States and many other industrialized nations There are two types of AMD the andquot dryandquot and andquot wetandquot forms Dry AMD is a chronic disease that usually causes variable degree of visual impairment In contrast in wet AMD which affects of AMD patients the disease progresses rapidly to blindness if left untreated with severe lesions in Bruchandapos s membrane and retinal pigment epithelium RPE layer and concomitant choroidal neovascularization CNV In the current standard of care wet AMD patients receive anti vascular endothelial growth factor VEGF agents Although this therapy improves visual acuity in a substantial proportion of patients most patients do not achieve substantial visual improvement and a third of treated eyes progress to legal blindness Half of the eyes receiving VEGF experience persistent CNV leakage fibrotic scarring and or geographic atrophy Further frequent intravitreal injections represent a significant financial burden and entail risks that include pain bleeding infection traumatic injury and retinal tear detachment and degeneration A novel therapeutic strategy which improves outcomes in a less invasive manner reducing risk while providing long term inhibition of angiogenesis with acceptable safety profile is an urgent and unmet medical need iVeena has developed and patented US Patent No B an intracellular anti angiogenic therapy relying on expression of Flt k intraceptors selectively at the lesions of Bruchandapos s RPE and choroid to sequester VEGF from secretion and also prevent intracellular autocrine loops Our early research has demonstrated that a single intravenous dose of Flt k intraceptors nanoparticles inhibits laser induced CNV in mice rat and monkey CNV models without major side effects This early research is attracting the attention of the marketplace Novartis in Cambridge MA has requested sample materials from iVeena to explore the efficacy of Flt k nanoparticles in their in house CNV models Please see the attached Material Transfer Agreement between iVeena and Novartis With SBIR funding iVeena is planning to further develop this novel approach The specific aims of this Phase I SBIR project are Aim To perform a Flt k nanoparticle dose ranging study Aim Establish the safety of the treatment All the proposed studies will be performed using the established laser induced CNV model in mice The successful completion of these studies will identify a safe and efficacious therapeutic dose that is feasible for manufacturing under GMP conditions to test in higher primates for proof of concept POC studies in Phase II application of this project PUBLIC HEALTH RELEVANCE Age related macular degeneration AMD is a leading cause of blindness in America afflicting an estimated million people worldwide There are two types of AMD the andquot dryandquot and andquot wetandquot forms Dry AMD is a chronic disease that usually causes variable degree of visual impairment In contrast wet AMD affects of AMD patients and rapidly progresses to blindness if left untreated Currently the primary treatment for wet AMD consists of monthly injections of antibody based inhibitors into the eye Although this therapy improves vision in a substantial proportion of patients almost a third of treated patients continu to lose visual acuity and progress to legal blindness Further frequent intravitreal injections represent significant risks that include bleeding infection traumatic injury and retinal detachment as well as expense We developed a novel therapy which improves outcomes in a less invasive manner reducing risks and costs while providing long term suppression of AMD in animal models We propose to optimize the dose and establish safety and efficacy of the treatment in a mice AMD model so that we can lay the foundation for human testing