Manufacturing Development and Commercial Readiness of an Adeno-Associated Virus-Based Gene Therapy for the Treatment of Leber Congenital Amaurosis Type 1

Atsena Therapeutics, Inc., Durham NC

Investigators

Abstract

Project Summary/Abstract Atsena Therapeutics is developing ATSN-101, an adeno-associated virus (AAV)-based gene therapy product, indicated for treatment of Leber congenital amaurosis type 1 (LCA1). LCA1 is a childhood blinding disease, for which no treatments currently exist. Atsena has compelling clinical data with ATSN-101. In a Phase 1/2 trial, treated LCA1 patients experienced clinically meaningful improvements in retinal sensitivity and functional vision. Atsena is now readying ATSN-101 for use in a Phase 3 clinical trial, submission for approval by the Food and Drug Administration (FDA) and commercialization. The Direct to Phase II SBIR project aims to conduct the manufacturing development studies necessary to yield a Phase 3 and commercial-ready ATSN-101 product. Atsena has a clinical / commercial manufacturing platform in place, to which ATSN-101 will be adapted. The project will 1) employ statistical approaches to define optimal process parameters and acquire adequate process knowledge for FDA approval, 2) innovate product-specific analytical assays required for FDA approval and adopt the industry’s best methods for analytical testing, and 3) demonstrate ATSN-101 product comparability sufficient for FDA approval through analytical testing and a nonclinical study in a mouse model of LCA1. Atsena’s veteran biotech team is well-equipped to execute on the project plan. The project results will enable conduct of a Phase 3 clinical trial, preparation of a Biological License Application (BLA) for ATSN-101, and ultimately, commercialization of a gene therapy for LCA1 patients. LCA1 is rare, inherited retinal disease (IRD), readily treatable by gene therapy. LCA1 patients have severely abnormal retinal function but maintain relatively normal retinal structure throughout their lifetime. ATSN-101 could be an effective, vision-restoring treatment for all LCA1 patients, but will be particularly impactful for children. The consequences of extreme low vision, exacerbated in children, include dramatically increased likelihood of neuroatypical development, quantitatively and qualitatively reduced quality of life, and statistically increased lifelong risk of depression and mortality. This project is well- aligned with the mission of the National Eye Institute (NEI), to eliminate vision loss and improve quality of life through vision research. LCA1 patients have profoundly impaired vision but attained significantly improved retinal sensitivity and functional vision after ATSN-101 treatment. If proven effective, ATSN-101 could improve quality of life for LCA1 patients, reduce their dependence on caretakers, and reduce the overall socioeconomic impact of IRD in the United States. This project is also well-aligned with the missions of the National Institutes of Health (NIH) SBIR program, specifically, to increase private sector commercialization of innovations developed through federal funding. ATSN-101 has a short path to FDA approval and commercialization. If successful, Atsena could bring the first treatment for LCA1 to market with the help of federal funding.