The results support plan to advance lead program in ABCA4-related retinopathies into the clinic in 2024 and expansion into other ophthalmology indications.
According to a news release, the data demonstrate for the first time that a single subretinal administration of a DNA payload encoding the human ABCA4 gene resulted in durable (12-month) expression of human ABCA4 protein in adult porcine retinas. The expression levels achieved are believed to be sufficient to result in therapeutic benefit in individuals living with ABCA4-related retinopathies. Based on the encouraging results, the company plans to advance its IND-enabling studies and future clinical development.
In the study, full-length ABCA4 DNA was packaged into Intergalactic's proprietary C3DNA (covalently closed and circular DNA) cargo platform, and was delivered using COMET, Intergalactic's proprietary system for targeted delivery of C3DNA. Full results from the study will be presented at an upcoming medical meeting.
José Lora, PhD, chief scientific officer of Intergalactic Therapeutics, the company is encouraged of the findings from these preclinical studies.
“With these data, we have clearly demonstrated the feasibility of electro-transfer delivery of non-viral C3DNA expressing the full-length human ABCA4gene to relevant cell types in the retina,” Lora said. “We have also confirmed persistence of ABCA4expression 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 non-viral 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."
"As a retina specialist with expertise in inherited retinal degeneration as well as a number of acquired eye conditions, I believe non-viral gene therapy offers significant potential in this difficult to treat area," Mark Pennesi, MD, PhD, professor of Ophthalmology and Chief at OHSU Casey Eye Institute and a member of Intergalactic's Ophthalmology Advisory Panel, said in the news release. "These findings provide proof of concept and further hope that non-viral gene therapy may revolutionize the field for patients who currently have limited or no treatment options."
According to the company, its non-viral gene therapy platform is designed to overcome limitations of standard adeno-associated virus (AAV) gene therapy technologies, including vector capacity limitations and vector-related safety concerns, and unlock the potential of non-viral gene therapies for a wide range of diseases. Specifically, C3DNA is designed to enable therapeutic delivery of large genes, while eliminating safety concerns associated with viral vectors and allowing the potential for redosing. COMET is a precise and tunable electro-transfer-based method for local delivery of C3DNA payloads to various tissues of interest.
Due to high unmet need, amenability to local gene delivery, and the significant limitations of viral-based gene therapy, Intergalactic has prioritized ophthalmology and is advancing a lead program targeting ABCA4-related retinopathies. These retinopathies, the most common inherited retinal disease, currently have no approved treatments.
Intergalactic plans to move its lead ABCA4 program into the clinic in 2024. The company also has pipeline programs targeting other ophthalmology indications and is evaluating the broader applicability of the platform to other tissue types.
"Intergalactic's mission is to overcome the limitations of viral-based gene therapy and develop a best-in-class non-viral alternative," Theresa G.H. Heath, MD, MBA, CEO of Intergalactic Therapeutics, said in a news release. "We look forward to continuing to advance our IND-enabling ABCA4 studies into the clinic and progressing additional pipeline programs where our innovative approach holds the potential to unlock the promise of non-viral gene therapy for patients."
About ABCA4-Related Retinopathies
ABCA4-related retinopathies, including Stargardt disease, cone-rod dystrophy, and retinitis pigmentosa, lead to degeneration of rods and cones and cause vision loss that often starts in childhood or adolescence, ultimately leading to blindness.
According to the companies, these diseases are associated with mutations in the ABCA4 gene, more than 900 of which have been described. There are currently no approved treatments for ABCA4-related retinopathies and, while replacement with wild-type ABCA4 protein has the potential to slow or stop disease progression, standard AAV gene therapy platforms are not appropriate for addressing these diseases due to the large size of the gene and the growing safety concerns associated with viral vectors. Intergalactic's novel platform bypasses these drawbacks and enables local delivery of non-viral gene therapy, representing a potentially transformative approach for addressing these blinding diseases.