Taking it straight to the eye

Vector platform delivers gene therapy to the retina

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NEW YORK & CLEVELAND—Abeona Therapeutics Inc., a clinical-stage biopharmaceutical company developing gene and cell therapies for serious diseases, reported new preclinical data showing that its AIM AAV204 vector led to robust transgene expression in the inner and outer retina when delivered intravitreally to non-human primates.
Presented at the Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting in Vancouver, British Columbia, the data demonstrate the potential of AAV204 to deliver gene therapy in an outpatient setting for a wide range of inherited and acquired retinal diseases. Prior data in mouse models have also shown that intravitreal administration of AAV204, based on Abeona’s AIM vector platform, results in robust transduction of retinal cells and broad retinal expression that can penetrate the photoreceptor and retinal pigmented epithelium layers of the eye.
In preclinical results, intravitreal administration of the novel AIM AAV204 capsid in non-human primates demonstrated broad transgene expression in the peripheral retina and intense expression in the fovea 25 days post-administration. AAV204 also transduced photoreceptor cells in retinal explants and transduced the outer retina, with positive green fluorescent protein (GFP) expression.
Non-human primate data were complemented by findings from mice models, which identified AAV204 as one of three lead candidate AIM capsids that demonstrate robust transduction of retinal cells. The data in mice showed that intravitreal administration resulted in broad retinal expression of AAV204 that penetrated to the photoreceptor and retinal pigmented epithelium layers.
As Dr. Tim Miller, president and chief scientific officer at Abeona Therapeutics, explained, “There are two ways to deliver gene therapy to the eye: subretinal surgical delivery and intravitreal injection. Natural AAV serotypes do not penetrate to the inner retina very well by intravitreal injection, historically requiring a more invasive approach to get the AAV to the target cells. Subretinal injections can deliver a gene therapy right to the target cells in the retina, but it involves a surgical procedure that has some risks. Our AIM AAV204 capsid is novel, with the specific ability to deliver genes to the inner and outer retina after intravitreal injection. Results from our non-human primate studies have shown that this special tropism enables AAV204 to deliver gene therapy effectively to the eye and potentially treat a range of both inherited and acquired retinal disorders.”
Miller said that Abeona’s AIM vectors were identified through a chimeric virus library, created by combining fragments of natural AAV vectors to produce chimeras with more specific tropisms for certain tissues than the natural serotypes. Because these chimeric vectors do not normally exist in nature, there is much lower potential for patients to have had an exposure that would result in an immune response. This enables the AIM vectors to be used as tools to deliver therapeutic genes to more patients.
“The route of delivery to get to a target organ is a critical aspect of a successful gene therapy, and our data suggest that the ability of the AIM vectors to evade immune responses to natural AAV capsids potentially allows us to target more diseases through multiple routes of administration—and possibly re-dose patients who were previously administered with natural AAV capsids,” he added.
Some AIM capsids can selectively target delivery of genetic payloads to various tissues in the body, including the eye, according to Miller. AAV204 was identified as one of a few lead candidate AIM capsids that demonstrate robust transduction of retinal cells after delivery to the eye. About 80 percent of eye diseases affect the photoreceptors in the retina, highlighting the importance of cellular targeting and reinforcing that the AIM vector platform can be an efficient tool in gene delivery.
Abeona’s AIM library contains more than 100 capsids with tissue tropisms selected for their potential to target a wide range of organs and multiple routes of delivery. The company is very encouraged by the new data and believes its capsids could lead to new therapies for a range of diseases and conditions. Abeona also plans to explore use of these capsids for gene replacement as well as other types of genetic therapies, including gene editing.
“As a result, we may have the opportunity to target multiple areas of unmet need that represent significant commercial opportunities in the years ahead,” Miller concluded.

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