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Opus Genetics secures NIH grant for LCA9 gene therapy IND-enabling studies

Opus Genetics secures NIH grant for LCA9 gene therapy IND-enabling studies

Opus Genetics has been awarded a USD 1.01 million National Eye Institute Small Business Innovation Research award to advance OPGx-NMNAT1, an AAV9-based gene augmentation therapy for LCA9, a subtype of Leber congenital amaurosis (LCA) caused by mutations in the nicotinamide mononucleotide adenylyl transferase 1 (NMNAT1) gene. The R44 Direct-to-Phase II grant will fund IND-enabling manufacturing and toxicology studies, with an IND submission to FDA as the stated endpoint.

LCA9 is an ultra-rare inherited retinal disease caused by mutations in NMNAT1 and currently has no approved treatment. OPGx-NMNAT1, formerly known as OPGx-003, originated in the laboratory of Eric Pierce at Mass Eye and Ear and Harvard Medical School and was licensed by Opus in 2021. The therapy delivers a codon-optimized human NMNAT1 complementary DNA via AAV9 under a ubiquitous CASI promoter, with the aim of restoring functional NMNAT1 expression in the retina. Opus has reported durable structural and functional rescue in an Nmnat1V9M/V9M mouse model for up to nine months and has completed a pre-IND meeting with FDA.

Opus Genetics already has a clinical-stage LCA program: OPGx-LCA5, an AAV8 gene augmentation therapy for LCA5, is in Phase I/II trials, with positive adult and pediatric data reported and an FDA meeting completed supporting advancement toward a pivotal trial. That existing regulatory and manufacturing infrastructure supports the IND pathway for OPGx-NMNAT1. Principal investigator Ashwath Jayagopal leads the program.

Opus is also advancing OPGx-LCA5, an AAV8 gene augmentation therapy for LCA5-associated retinal disease, and in July reached alignment with FDA on the design of a registrational Phase III trial, with dosing expected to begin in Q4 2026. The company has increasingly combined equity and strategic financing with program-specific non-dilutive funding across its inherited retinal disease pipeline. It raised USD 23 million in a registered direct offering in November 2025 and USD 25 million in a private placement in February 2026, before securing access to up to USD 155 million through an Oberland Capital financing facility in April.

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Gene replacement is already established in LCA through Spark Therapeutics' Luxturna for biallelic RPE65-associated retinal dystrophy, while multiple other genetically defined LCA subtypes are being pursued with experimental gene therapies.


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