Applied Genetic Technologies Corporation
May 5, 2014
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AGTC Data Presented at the ARVO Annual Meeting Support Development of Gene-Based Therapies for Achromatopsia

GAINESVILLE, Fla., May 5, 2014 (GLOBE NEWSWIRE) -- Applied Genetic Technologies Corporation (Nasdaq:AGTC), a clinical stage biotechnology company developing adeno-associated virus (AAV)-based gene therapies for the treatment of rare eye diseases, announced that Guo-jie Ye, Ph. D., Director, Research and Pre-Clinical Studies, presented preclinical data related to the company's achromatopsia gene therapy program yesterday in an oral session at the Association for Research in Vision and Ophthalmology (ARVO) annual meeting. ARVO is taking place from May 4 - 8, 2014, at the Orlando Convention Center in Orlando, Fl.

The abstract #837, titled "Development and Evaluation of Cone-Specific Promoters in Non-human Primates for Gene Therapy of Congenital Cone Diseases Including Achromatopsia," describes preclinical studies designed to evaluate the activity of several gene regulatory sequences in a variety of cell types within the eye. The goal of these studies was to identify a promoter sequence capable of directing efficient gene expression specifically within non-human primate (NHP) cone photoreceptors. Non-human primates have retinal anatomy and physiology nearly identical to that of humans. Consequently, a promoter sequence identified from a NHP study may be more relevant to gene regulation in human cone cells.

Achromatopsia (ACHM) is an inherited retinal disease characterized by complete loss of cone photoreceptor function, and people with ACHM have severe vision loss that renders patients legally blind. ACHM can be caused by mutations in several genes and mutations in a gene called cyclic nucleotide gated channel beta 3 (CNGB3) accounts for 50% of all cases of achromatopsia in Western countries. While there is currently no cure for ACHM, AGTC is developing a gene therapy product based on an adeno-associated virus (AAV) vector to enable expression of normal CNGB3 protein within cone photoreceptors and restore cone photoreceptor functions in patients. AGTC and its academic collaborators have previously demonstrated that subretinal delivery of gene sequences using an AAV vector restores cone responses in a dog model of ACHM.

"AGTC is committed to developing safe and effective gene-based therapies for inherited eye diseases, and achieving that goal requires designing vectors that express therapeutic levels of protein in the appropriate cell types," said Dr. Guo-jie Ye. "Our expertise in vector design and body of knowledge in the area of inherited eye diseases are key assets that enable us to develop vectors that are optimized for clinical benefit. The data presented yesterday underscore the importance of identifying promoters and other regulatory sequences that will function efficiently in humans."

Sue Washer, President and CEO, said, "The data also provide additional validation of the approach that AGTC is taking to develop an ACHM gene therapy that has the potential to provide long-lasting correction of the molecular cause of ACHM. We expect to initiate a phase 1/2 clinical trial in ACHM in 2015."

The oral presentation given at ARVO yesterday by Dr. Ye describes approaches used to design and construct a series of short promoter sequences (PR1.1, PR1.5, and PR1.7) based on the PR2.1 promoter, which is a 2.1 kb human red cone opsin promoter. The expression cassette of CNGB3 with the PR2.1 promoter has a size of > 5.2 kb and is well above the optimal size for packaging into an AAV capsid. As described in the presentation, animal studies, including an initial screening test in mice followed by a definitive NHP study, identified PR1.7 as a robust and cone-specific promoter. Among the promoter sequences tested (PR1.1, PR1.5, PR1.7 and PR2.1), the PR1.7 promoter was found to have comparable efficiency to the PR2.1 promoter in directing gene expression in mouse cone photoreceptors. PR.17, PR2.1, and also IRBP/GNAT2, a hybrid promoter developed at the University of Florida that has demonstrated robust, cone-specific activity in mouse and dog cones, were selected for further evaluation in a definitive NHP study using green florescent protein (GFP) as the reporter gene product. Among the three promoter sequences evaluated in NHP, the PR1.7 promoter resulted in the most robust gene expression. Intensive GFP expression was found in all three types of cone photoreceptors in every retinal section examined, and this expression was specific to cone photoreceptors. Variable levels of cone-specific GFP expression, mostly mild to moderate, was found in retina injected with AAV-GFP vectors containing PR2.1promoter sequence. No GFP expression was detected in any retinal sections injected with AAV-GFP vectors containing IRBP/GNAT2 promoter. Based on these findings, the authors conclude that PR1.7 is the preferred promoter for gene-based therapies targeting inherited cone diseases, and also emphasize the importance of evaluating promoter activity in NHPs in order to optimize expression for human ACHM patients.

About AGTC

AGTC is a clinical-stage biotechnology company that uses its proprietary gene therapy platform to develop products designed to transform the lives of patients with severe inherited orphan diseases in ophthalmology. AGTC's lead product candidates, which are each in the preclinical stage, focus on X-linked retinoschisis, achromatopsia and X-linked retinitis pigmentosa, which are rare diseases of the eye, caused by mutations in single genes, that significantly affect visual function and currently lack effective medical treatments.

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         Applied Genetic Technologies Corporation

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