IND-enabling safety and efficacy of RPESC-RPE-4W, an adult RPE progenitor cell therapy for dry age-related macular degeneration.

Dry age-related macular degeneration (AMD) is a prevalent blinding disorder characterized by loss of retinal pigment epithelium (RPE) cells and resulting central vision impairment. Here, we describe preclinical studies supporting an investigational new drug (IND) application for adult RPE stem cell-derived RPE (RPESC-RPE) cell replacement therapy. We establish donor-to-donor reproducibility and Good Manufacturing Practice (GMP) processes and evaluate the GMP cell product in preclinical studies conducted in accordance with Good Laboratory Practice principles. Efficacy experiments in Royal College of Surgeons rats show that subretinal implantation of the 4-week, postmitotic, progenitor-stage product (RPESC-RPE-4W) produces significant and durable vision rescue compared to vehicle control. Biodistribution and safety studies in immunocompromised Rowett Nude rats demonstrate a favorable safety profile, with no adverse effects related to the cell product. These studies underpin allowance of an ongoing phase 1/2a clinical trial.