- Simultaneous delivery of two optimized AAV vectors expands the therapeutic and commercial potential of AGTC’s industry-leading AAV platform by enabling delivery of DNA encoding larger proteins –
GAINESVILLE, Fla., and CAMBRIDGE, Mass., Nov. 5, 2019 – 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 that it has identified Stargardt disease as the second ophthalmology program in its previously announced preclinical pipeline expansion, which also includes a program targeting the dry form of age-related macular degeneration (AMD). The company is also reporting proof-of-concept expression data for its Stargardt disease gene therapy candidate in non-human primates (NHPs).
Stargardt disease, the most common form of inherited macular degeneration, occurs in 1 in 8,000-10,000 individuals and most often results from mutations in the ABCA4 gene. Loss of functional ABCA4 protein leads to the accumulation of toxic substances in photoreceptors, resulting in photoreceptor death and progressive vision loss. A key challenge in developing an AAV-based gene therapy for the treatment of Stargardt disease is that the DNA sequence encoding the ABCA4 protein exceeds the payload capacity of AAV vectors. AGTC’s Stargardt disease program effectively addresses this challenge by dividing the coding sequence into two separate AAV vectors. Once inside the cell, the two DNA fragments recombine to form the complete coding sequence, which produces full length, functional ABCA4 protein.
“The expansion of our preclinical pipeline to include Stargardt disease and dry AMD demonstrates the broad therapeutic and commercial utility of our proprietary AAV gene delivery platform,” said Sue Washer, President and CEO of AGTC. “Our Stargardt disease program underscores our ability to leverage our expertise in AAV vector and genome engineering to expand AAV gene therapy into new indications that require delivery of larger DNA payloads. Dry AMD represents a compellingly large market opportunity given that the disease affects over 24 million people globally. Each of these preclinical programs builds on our industry-leading capabilities in gene therapy for retinal diseases and will leverage our expanding expertise in designing and implementing preclinical and clinical studies that are optimized for success.”
William Hauswirth, PhD, a leading innovator in AAV gene therapy at the University of Florida and a long-term academic collaborator with AGTC, and his colleagues at the University of British Columbia, recently published data demonstrating that a hybrid ABCA4 dual AAV vector system was safe and provided therapeutic benefit in a mouse model of Stargardt disease.1 Researchers at AGTC optimized the vectors
used in Dr. Hauswirth’s study for administration to NHPs.
In a 13-week study, subretinal injection of AAVs prepared at AGTC encoding the N-terminal fragment and C-terminal fragment of human ABCA4, which was tagged to distinguish it from the naturally occurring non-human primate ABCA4 protein, resulted in clear detection of full length recombinant human ABCA4 protein. The protein was detected in tissue punches harvested from inside the subretinal bleb, but not in the untreated surrounding tissue, confirming the specificity and effectiveness of the vector administration. These results in NHPs are an important technical advance for the use of dual AAV vector expression systems in retinal gene therapy. Based on the results of this study, AGTC is continuing therapeutic development of its optimized dual vector system for the treatment of Stargardt disease.
“Our recent publication provided important proof-of-concept data supporting the safety and therapeutic utility of using a dual AAV vector system to deliver and express the ABCA4 protein,” said William W. Hauswirth, PhD, Professor of Ophthalmology and the Maida and Morris Rybaczki Eminent Scholar Chair in Ophthalmic Sciences in the Department of Ophthalmology at the University of Florida. “AGTC’s demonstration that this approach is safe and results in ABCA4 protein expression in NHPs following subretinal injection of their optimized vectors is an important milestone in advancing gene therapy for Stargardt disease toward the clinic.”
1 Dyka FM, Molday LL, Chiodo VA, Molday RS and Hauswirth WW. Dual ABCA4-AAV vector treatment reduces pathogenic retinal A2E accumulation in a mouse model of autosomal recessive Stargardt disease. Hum Gene Ther. 2019 Sep 30. doi: 10.1089/hum.2019.132.
AGTC is a clinical-stage biotechnology company that uses a proprietary gene therapy platform to develop transformational genetic therapies for patients suffering from rare and debilitating diseases. Its initial focus is in the field of ophthalmology, in which it has active clinical trials in X-linked retinitis pigmentosa (XLRP) and achromatopsia (ACHM CNGB3 & ACHM CNGA3). In addition to its clinical trials, AGTC has preclinical programs in optogenetics, adrenoleukodystrophy (ALD), which is a disease of the central nervous system (CNS) and other CNS, ophthalmology and otology indications. The optogenetics program is being developed in collaboration with Bionic Sight. The otology program is being developed in collaboration with Otonomy. AGTC has a significant intellectual property portfolio and extensive 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.
About X-linked Retinitis Pigmentosa (XLRP)
XLRP is an inherited condition that causes progressive vision loss in boys and young men. Characteristics of the disease include night blindness in early childhood and progressive constriction of the visual field. In general, XLRP patients experience a gradual decline in visual acuity over the disease course, which results in legal blindness around the 4th decade of life. AGTC was granted U.S. Food and Drug (FDA) orphan drug designation in 2017, as well as European Commission orphan medicinal product designation in 2016, for its gene therapy product candidate to treat XLRP caused by mutations in the RPGR gene.
About Achromatopsia (ACHM)
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.
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, financial guidance, 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. Risks and uncertainties that may cause actual results to differ materially include, among others: gene therapy is still novel with only a few approved treatments so far; AGTC cannot predict when or if it will obtain regulatory approval to commercialize a product candidate or receive reasonable reimbursement; uncertainty inherent in clinical trials and the regulatory review process; risks and uncertainties associated with drug development and commercialization; factors that could cause actual results to differ materially from those described in the forward-looking statements are set forth under the heading “Risk Factors” in the Company’s Annual Report on Form 10-K for the fiscal year ended June 30, 2019, 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, we assume 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.
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