GAINESVILLE, Fla., and CAMBRIDGE, Mass., April 20, 2016 (GLOBE NEWSWIRE) -- Applied Genetic Technologies Corporation (Nasdaq:AGTC), a biotechnology company conducting human clinical trials of adeno-associated virus (AAV)-based gene therapies for the treatment of rare diseases, today announced the publication of two studies that provide support for the Company’s planned clinical investigation of its novel investigational gene therapy candidate for treating achromatopsia caused by mutations in the CNGB3 gene. Results, evaluating toxicology and biodistribution profiles in mouse and non-human primate models, were published online in the peer-reviewed journal Human Gene Therapy Clinical Development and appear in the March print issue.
“Achromatopsia is a serious inherited retinal disorder characterized by markedly reduced visual acuity, extreme light sensitivity and absence of color discrimination,” said Guo-jie Ye, Ph.D., AGTC’s Senior Director of Research and Pre-Clinical Studies and lead author on both manuscripts. “Currently there are no effective treatments for this disease. We are encouraged by these results to continue our planning for clinical evaluation of an AAV-based gene therapy treatment in patients with achromatopsia caused by CNGB3 mutations.”
The two studies evaluated the toxicology and bioavailability of subretinal injection of rAAV2tYF-PR1.7-hCNGB3, an AAV vector containing a copy of the CNGB3 gene, at two different doses. The first study in CNGB3-deficient (knockout) mice demonstrated that injection of the vector was well-tolerated and not associated with any clinically important toxicological findings. Biodistribution analysis showed that detection of vector DNA was limited primarily to high levels in vector-injected eyes, with little or no vector DNA in other tissues, showing that the treatment was specific to its intended target and did not affect surrounding tissues. This study also evaluated the efficacy of the treatment, showing increased cone-mediated ERG responses, a measure of electrical signaling in retinal cells, in vector-treated eyes in 90 percent of animals in the higher-dose group.
The second study demonstrated that injection of the vector in normal cynomolgus macaques resulted in dose-related ocular inflammation that improved over time. Biodistribution studies demonstrated high levels of vector DNA in the injected eye but minimal or no vector DNA in any other tissue. This study in normal animals was not designed to evaluate efficacy.
“These results further underscore the potential clinical utility of AGTC’s novel AAV-based gene therapies for treating inherited retinal conditions,” said Sue Washer, President and CEO of AGTC. “These studies reinforce the prior evidence in animal models that suggests that our achromatopsia gene therapy candidate, delivered as a one-time injection, has the potential to provide long-lasting vision improvement in humans and we are looking forward to advancing the program into clinical studies.”
AGTC is developing products for achromatopsia resulting from mutations in both the CNGB3 and CNGA3 genes, which together account for approximately 75 percent of the total achromatopsia patient population. The Company previously received orphan drug designation from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for its investigational gene therapy product for the treatment of achromatopsia caused by mutations in the CNGA3 gene.
Recent studies conducted by several of AGTC research partners including University of Florida, Hadassah-Hebrew University Medical Center, The Volcani Center and the Hebrew University of Jerusalem showed that in sheep affected by achromatopsia caused by mutations in the CNGA3 gene, delivery of an AAV vector carrying a healthy copy of the CNGA3 gene was able to restore cone photoreceptor function and the ability to navigate an obstacle maze course.
About Achromatopsia
Achromatopsia is an inherited retinal disease, which is present from birth and is characterized by the lack of cone photoreceptor function. The condition results in markedly reduced visual acuity, extreme light sensitivity causing day blindness, and complete loss of color discrimination. Best-corrected visual acuity in persons affected by achromatopsia, even under subdued light conditions, is usually about 20/200, a level at which people are considered legally blind. The incidence rate for achromatopsia is approximately one in 30,000 people, and it is estimated that there are approximately 10,000 people in the United States and 17,000 people in Europe with achromatopsia.
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 diseases, with an initial focus in ophthalmology. AGTC's lead product candidates are designed to treat inherited orphan diseases of the eye, caused by mutations in single genes that significantly affect visual function and currently lack effective medical treatments.
AGTC's product pipeline includes six named ophthalmology development programs across five targets (X-linked retinoschisis, X-linked retinitis pigmentosa, achromatopsia, wet age-related macular degeneration and blue cone monochromacy), non-ophthalmology programs in alpha-1 antitrypsin deficiency and adrenoleukodystrophy and early research studies in additional indications. AGTC employs a highly targeted approach to selecting and designing its product candidates, choosing to develop therapies for indications having high unmet medical need, clinical feasibility and commercial potential. AGTC has a significant intellectual property portfolio and expertise in the design of gene therapy products including capsids, promoters and expression cassettes, as well as expertise in the formulation, manufacture and physical delivery of gene therapy products.
Forward Looking Statements
This release contains forward-looking statements that reflect AGTC's plans, estimates, assumptions and beliefs. These statements relate to a variety of matters, including but not limited to, the anticipated progress of AGTC’s clinical and pre-clinical programs and the anticipated utility of AAV vectors made using AGTC’s proprietary manufacturing method and progress of or financial implications of AGTC’s various partnership activities. Forward-looking statements include all statements that are not historical facts and can be identified by terms such as "anticipates," "believes," "could," "seeks," "estimates," "expects," "intends," "may," "plans," "potential," "predicts," "projects," "should," "will," "would" or similar expressions and the negatives of those terms. Actual results could differ materially from those discussed in the forward-looking statements, due to a number of important factors, which include, but are not limited to, the following: no gene therapy products have been approved in the United States and AGTC cannot predict when or if it will obtain regulatory approval to commercialize a product candidate; uncertainty regarding AGTC's ability to achieve the expected benefits from its collaborations with Biogen and others, including as a result of risks and uncertainties associated with drug development and commercialization; AGTC relies on third parties to conduct, supervise and monitor its clinical trials and to conduct certain aspects of its research, product manufacturing and protocol development; and increased regulatory scrutiny of gene therapy and genetic research could damage public perception of AGTC's product candidates or adversely affect AGTC's ability to conduct its business. Additional factors that could cause actual results to differ materially from those described in the forward-looking statements are set forth under the heading "Item 1A—Risk Factors" in AGTC's Annual Report on Form 10-K for the fiscal year ended June 30, 2015, as filed with the SEC. Given these uncertainties, you should not place undue reliance on these forward-looking statements. Also, forward-looking statements represent management's plans, estimates, assumptions and beliefs only as of the date of this release. Except as required by law, AGTC assumes no obligation to update these forward-looking statements publicly or to update the reasons actual results could differ materially from those anticipated in these forward-looking statements, even if new information becomes available in the future.