ABCA4 Retinopathy Gene Therapy Demonstrates Efficacy in Preclinical Study


Intergalactic Therapeutics’ IG-002 utilizes a proprietary non-viral delivery method.

Intergalactic Therapeutics’ IG-002, an investigational nonviral gene therapy intended to treat retinopathies associated with mutations in the ABCA4 gene, demonstrated the ability to affect expression of the ABCA4 protein for 12 months in adult porcine retinas after a single subretinal administration.1

IG-002 consists of full-length ABCA4 DNA that is packaged in the company’s covalently closed and circular (C3) DNA cargo platform and delivered via a proprietary electro-transfer-based targeted delivery system for C3DNA, referred to as COMET. C3DNA is intended to allow for the delivery of larger DNA payloads than is possible with viral vectors and to avoid safety concerns associated with viral vectors. Intergalactic Therapeutics reported that it believes the expression levels achieved in its preclinical research with IG-002 would be sufficient to provide therapeutic benefit in human patients with ABCA4-related retinopathies.

The company noted that full results would be presented at an upcoming clinical conference. Furthermore, Intergalactic Therapeutics stated that it has plans to conduct IND-enabling studies, with the expectation that IG-002 could enter clinical trials in 2024. The company is also evaluating whether the C3DNA platform can be applied to other indications.

"We are highly encouraged by the promising and unprecedented findings from these preclinical studies," José Lora, PhD, the chief scientific officer of Intergalactic Therapeutics, said in a statement.1 "With these data, we have clearly demonstrated the feasibility of electro-transfer delivery of nonviral C3DNA expressing the full-length human ABCA4 gene to relevant cell types in the retina. We have also confirmed persistence of ABCA4 expression for at least 12 months in vivo in photoreceptors—the longest time point evaluated to date. These findings underscore the promise of Intergalactic's innovative nonviral approach to expanding the gene therapy universe and address the unmet needs of patients with ABCA4-related retinopathies and other historically untreatable diseases. We are eager to advance our research and move this promising program toward clinical development."

Intergalactic Therapeutics is not the only company developing a gene therapy for ABCA4-related retinopathy. Nanoscope Therapeutics’ multicharacteristic opsin (MCO) optogenetic gene therapy MCO-010 is currently being evaluated in a phase 2 STARLIGHT clinical trial (NCT05417126) for the treatment of Stargardt disease.2 MCO-010 was granted fast track designation for this indication by the FDA in January of this year. MCO-010 is also being evaluated for the treatment of retinitis pigmentosa in the phase 2b/3 RESTORE clinical trial (NCT04945772). It received fast track designation for that indication from the FDA in October of last year.3 MCO-010 uses an adeno-associated virus vector-based delivery method.

"As a retina specialist with expertise in inherited retinal degeneration as well as a number of acquired eye conditions, I believe nonviral gene therapy offers significant potential in this difficult to treat area," Mark Pennesi, MD, PhD, a professor of ophthalmology and chief at OHSU Casey Eye Institute and a member of Intergalactic's Ophthalmology Advisory Panel, added to Lora’s statement.1 "These findings provide proof of concept and further hope that nonviral gene therapy may revolutionize the field for patients who currently have limited or no treatment options."

1. Intergalactic Therapeutics announces positive preclinical results of its non-viral gene therapy platform in ABCA4 retinopathies. News release. Intergalactic Therapeutics. March 15, 2023. Accessed March 16, 2023.
2. Nanoscope Therapeutics receives fast track designation by the FDA for MCO-010 for the treatment of Stargardt disease. News release. Nanoscope Therapeutics. January 30, 2023. Accessed March 16, 2023.
3. Nanoscope Therapeutics receives fast track designation by the FDA for MCO-010 for the treatment of retinitis pigmentosa. News release. Nanoscope Therapeutics Inc. October 10, 2022. Accessed March 17, 2023.
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