ASGCT 2023: Abeona Therapeutics announces preclinical data from its AAV ophthalmology program

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Abeona Therapeutics Inc. announced new data regarding three internally developed preclinical gene therapy product candidates from its adeno-associated virus (AAV) ophthalmology program being presented this week presented at the 26th annual meeting of the American Society of Gene & Cell Therapy (ASGCT), taking place through Saturday in Los Angeles, California.

“The preclinical proof-of-concept data being presented at ASGCT provides early evidence of the potential of our proprietary AAV capsids and gene constructs to express the recombinant protein in target tissues and rescue mutant phenotypes in mouse disease models,” Brian Kevany, PhD, chief technical officer and head of Research at Abeona, said in a news release. “We look forward to pre-Investigational new drug application meetings with the FDA for two of our programs to take place in the second quarter of 2023.”

On Wednesday, in a presentation titled “In Vivo Production of Full-Length ABCA4 Protein Following Cre-Mediated Recombination from Dual AAV Vectors in ABCA4-/- Mice,” Paul Wille, PhD, director, Product Development, Abeona Therapeutics presented key findings: A dual AAV vector strategy using Cre recombinase efficiently reconstituted the ABCA4 gene, leading to full-length hABCA4 protein expression both in vitro via viral transduction of HEK293 cells and in vivo in photoreceptor cells after subretinal injection into ABCA4-/- mouse eyes.

The company noted in the news release Cre-mediated recombination of ABCA4 was confirmed by mRNA sequencing of RNA from transfected HEK293 cells and AAV-dosed animals.

Moreover, it noted immunohistochemistry results confirmed correct localization of recombinant hABCA4 protein in photoreceptor cells.

In the presentation set for today, titled “ABO-503, a Novel Gene Therapy for Treatment of X-Linked Retinoschisis,” Joseph Fogerty, PhD, senior scientist, Product Development, Abeona Therapeutics will present key findings: Robust RS1 expression was observed in photoreceptor cells near the injection site and in the adjacent inner retina in mutant mice six months after treatment with ABO-503.

RS1 expression was associated with improvement in cone photoreceptor density and increased thickness of the photoreceptor outer nuclear layer.

Full-field flicker electroretinogram (ERG) analysis showed significant improvement in cone photoreceptor function.

On Friday, in a presentation, titled “AAV Gene Therapy for Autosomal Dominant Optic Atrophy Caused by Mutation in the Opa1 Gene,” Rachel Stupay, PhD, senior scientist, Product Development, Abeona Therapeutics will present key findings: Vectors expressing Opa1 showed robust expression at both RNA and protein levels both in vitro and in vivo.

In Opa1 knockout mouse fibroblasts, isoform variants 1, 5 and 7 expressed both RNA and protein with each variant corresponding to the expected cleavage pattern.

Abeona, a clinical-stage biopharmaceutical company developing cell and gene therapies for a number of diseases, noted in a news release its preclinical programs are investigating the use of novel adeno-associated virus (AAV) strategies in therapies for serious genetic eye diseases.

The company noted the most common form of Stargardt disease is caused by mutations in the ABCA4 gene, which prevents removal of toxic compounds from photoreceptor cells that results in photoreceptor cell death and progressive vision loss. ABO-504 is designed to efficiently reconstitute the full-length ABCA4 gene by implementing a dual AAV-vector strategy using the Cre-LoxP recombination system.

According to the company, XLRS is a rare, monogenic retinal disease that results in the irreversible loss of photoreceptor cells and severe visual impairment. XLRS is caused by mutations in the RS1 protein, which is normally secreted by retinal photoreceptors and bipolar neurons and functions to mediate cell-cell adhesion. ABO-503, composed of a functional human RS1 packaged in the novel AIM capsid AAV204, has shown preclinical efficacy following delivery to the retina in a mouse model of XLRS.

ADOA, a form of hereditary vision loss associated with retinal ganglion cell (RGC) death, is predominantly caused by mutations in the Opa1 gene. ABO-505 is designed to express a functional copy of human Opa1 in the retina following para-retinal injection. ABO-505 aims to take advantage of the robust optic nerve and RGC transduction ability of AAV204 to deliver its genetic payload to the cells most affected by ADOA.