FDA Clears IND for Opus Genetics’ OPGx-BEST1 Gene Therapy

Opus Genetics has received Investigational New Drug (IND) clearance from the U.S. Food and Drug Administration (FDA) for OPGx-BEST1, its gene therapy candidate for the treatment of BEST1-related inherited retinal disease (IRD). This regulatory milestone paves the way for the initiation of a Phase 1/2 clinical trial in the second half of 2025.

Addressing an Untreated Retinal Condition

BEST1-related IRD, also known as Best disease or vitelliform macular dystrophy, is a rare inherited retinal disorder caused by mutations in the BEST1 gene. These mutations result in progressive macular degeneration, often leading to significant vision loss or blindness. Clinical features include retinal lesions and symptoms such as dimness of vision, metamorphopsia, and scotoma.

The disease mechanism involves disruption of the BEST1 channel, a calcium-activated chloride channel critical for ion transport within retinal pigment epithelium (RPE) cells. When functioning properly, this channel helps maintain homeostasis between rod and cone photoreceptors and the RPE. Mutations in the BEST1 gene impair this homeostatic balance, causing degradation of the interphotoreceptor matrix (cIPM) and the microvilli (cMV) connections with the RPE. As a result, vitelliform lesions form between the RPE and Bruch’s membrane (BM)/choroid (CH), eventually leading to RPE atrophy and photoreceptor cell death, resulting in progressive vision loss.

A Gene Therapy Approach to Restoring Function

OPGx-BEST1 is developed using Opus Genetics’ proprietary adeno-associated virus (AAV)-based gene therapy platform. The therapy is engineered to deliver a functional copy of the BEST1 gene directly into the RPE cells, targeting the root cause of the disease by replacing the faulty gene.

The upcoming Phase 1/2 clinical trial will be a multi-center, open-label study evaluating the safety, tolerability, and preliminary efficacy of a single subretinal injection of OPGx-BEST1. The study will enroll patients with genetically confirmed BEST1-related IRD, and initial data is expected in the first quarter of 2026.

Commenting on the IND clearance, George Magrath, MD, CEO of Opus Genetics, stated:

“BEST1-related IRDs have no approved treatments today, leaving patients and families with uncertainty about the future of their vision. The OPGx-BEST1 trial will be our third ongoing clinical program, reflecting the depth of our pipeline and our commitment to advancing multiple therapies in parallel for patients with urgent, unmet needs.”