Human iPSC derived organoid therapeutics for the treatment of inherited blindness

About This Grant

Project Summary Inherited retinal diseases (IRDs) are a group of genetic blinding disorders that cause progressive vision loss, often resulting in blindness by early to mid-adulthood. In addition to economic burden, blindness and visual impairment have severe implications on quality of life for patients. The most common form of IRD, retinitis pigmentosa (RP), affects over 2 million people worldwide and approximately 100,000 in the US alone. With causative mutations identified in over 100 genes so far, the genetic heterogeneity underlying RP is a major barrier to treatment. No single gene accounts for more than 30% of the patient population, highlighting a massive unmet need for a gene-agnostic therapeutic that can treat many forms of RP. The goal of this Phase I STTR program is to develop AGN-001, a first-in-class, gene-agnostic, off-the- shelf retinal cell therapy to restore photoreceptor function in patients with IRDs. Agnos Therapeutics, Inc. (AgnosTx) was founded on the pioneering research from Mandeep Singh, MD, PhD and Robert Johnston, PhD of Johns Hopkins University, which showed that transplanted retinal cells restore photoreceptor function through cellular component transfer (CCT). CCT involves transfer of functional proteins from donor cells to diseased host photoreceptors through intercellular nanotubes, thus complementing a multitude of disease-causing mutations. AgnosTx’s CCT-based cell therapy, AGN-001, uniquely rescues existing patient photoreceptor function at earlier stages of disease, independent of gene mutation. This differentiates it from other retinal cell therapies or single- gene approaches, as it works without the need for synapse formation and cell integration. Previous studies in multiple mouse models of IRD have shown that transplanted wildtype photoreceptors can rescue retinal function through CCT. During this Phase I program, AgnosTx will collaborate with Drs. Johnston and Singh at Johns Hopkins to develop AGN-001 as a therapeutic suitable for preclinical evaluation and advance towards clinical studies. Aims include: 1) adapting the manufacturing process towards current Good Manufacturing Practices (cGMP) compliance; 2) generating and validating reporter lines to demonstrate the transfer of therapeutically relevant proteins by AGN-001; and 3) assessing subchronic toxicity and CCT efficiency of AGN-001 in vivo using a co-transplant strategy. Successful completion of these aims will provide the essential proof-of-concept and safety data to de-risk the program for investors and collaborators. This will enable future Phase II efforts focused on cGMP manufacturing scale-up and Good Laboratory Practices (GLP) toxicology studies to support an Investigational New Drug (IND). Our ultimate goal is to provide a broadly applicable treatment option for most patients with retinitis pigmentosa, a US market valued at over $14 billion, addressing a significant unmet need and patient burden.