GAINESVILLE, Fla. and CAMBRIDGE, Mass., Jan. 07, 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 eye diseases, today announced preclinical data evaluating cone-specific promoters for use in gene therapy of achromatopsia (ACHM) and other retinal diseases. Results were published online in the peer-reviewed journal Human Gene Therapy and will appear in the January print issue.
In the study, AGTC investigators designed and constructed a series of short promoter sequences (PR1.1, PR1.5, and PR1.7) based on the 2.1 kb human L-opsin promoter (previously shown to efficiently and selectively drive gene expression in cone cells of mice and dogs). The novel short promoters were first evaluated for their efficiency and specificity in driving green fluorescent protein (GFP) expression in normal mice and cynomolgus macaques. The promoters were then tested for their ability to rescue cone function in a mouse disease model of achromatopsia associated with mutations in the CNGB3 gene. Mutations in CNGB3 are the underlying genetic cause of approximately half of achromatopsia cases in humans.
When tested in mice, each of the newly designed promoters directed high expression of GFP within photoreceptors. Based on these encouraging results, a subset of the promoters was selected for study in nonhuman primates. In this study, subretinal injection of an AAV-GFP vector containing the PR1.7 promoter led to strong and specific GFP expression in all cone photoreceptor types (including L-, M-, and S- cones, corresponding to red, green, and blue cones in humans). When tested in a CNGB3 mouse mutant model of achromatopsia, subretinal injection of an AAV-CNGB3 vector containing the PR1.7 promoter rescued cone function.
“These critical data informed the design of the CNGB3 expression cassette that AGTC is using in our human achromatopsia clinical study,” noted Sue Washer, President and CEO of AGTC.
This multiple-site clinical study will assess AGTC’s novel recombinant AAV vector expressing CNGB3 (rAAV2tYF-PR1.7-hCNGB3) in patients with congenital ACHM caused by mutations in the CNGB3 gene. The primary and secondary endpoints of the study will be safety and efficacy, respectively.
“These new preclinical data reinforce previous findings suggesting that novel AAV-based gene therapies may be effective in treating rare inherited retinal diseases. We look forward to advancing our clinical program and hope the resulting data will form the basis for a safe and effective therapy for ACHM-B3 achromatopsia,” Ms. Washer added.
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 in ophthalmology. AGTC's lead product candidates focus on 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 (XLRS), x-linked retinitis pigmentosa (XLRP), achromatopsia, wet age-related macular degeneration and blue cone monochromacy (BCM)), one non-ophthalmology program (alpha-1 antitrypsin deficiency) and proof-of-concept data in multiple 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. Forward-looking statements include information concerning possible or assumed future results of operations, business strategies and operations, preclinical and clinical product development and regulatory progress, potential growth opportunities, potential market opportunities and the effects of competition. 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; AGTC relies on third parties to conduct, supervise and monitor its clinical trials and to conduct certain aspects of its product manufacturing and product 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 include those described in the forward-looking statements are set forth under the heading " Item 1A—Risk Factors" in the 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.