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Antisense Oligo Is Drug Candidate for Human Retinal Neovascular Diseases

Gene Signal, a Swiss company focused on developing innovative drugs to manage angiogenesis-based conditions, announced on May 8, 2012 that positive data from a study of aganirsen (GS-101, eye drops) in a nonhuman primate model of choroidal neovascularization has been presented at the 2012 ARVO Annual Meeting in Fort Lauderdale, Florida. Topical administration of aganirsen was found to inhibit neovascular growth and leakage in this model and strongly suggests a role for the drug candidate in human retinal neovascular diseases such as wet age-related macular degeneration (AMD) and ischemic retinopathy. Gene Signal's aganirsen is an antisense oligonucleotide that is expected to complete a phase III trial for the treatment of progressive neovascularization in the cornea in 2012. Clinical studies in retinal diseases are schedule to begin during the second quarter of 2012. "This study demonstrates the ability of aganirsen to address neovascularization formation in the retina by inhibiting the expression of the angiogenic protein IRS-1. Importantly, this is achieved without affecting normal vascularisation," noted Dr. Matthew Lawrence of RxGen, Inc, who presented the data. "With the demand for new, effective antiangiogenic agents that are easier to use in the treatment of several eye diseases growing, we believe these data strongly support a role for aganirsen." Aganirsen blocks pathological neovascularization by inhibiting IRS-1. Clinical studies to date have shown that aganirsen is able to safely and effectively inhibit the development of progressive corneal neovascularization secondary to infectious keratitis or chemical burns, both of which could lead to corneal graft replacement. "A topical agent for neovascular disease would revolutionize treatment. There is a huge unmet need for many opthalmological diseases including AMD, ischemic retinopathy, and certain forms of glucoma," noted Eric Viaud, CEO of Gene Signal. "To confirm the many advantages that topical aganirsen could offer over currently available drugs, we intend to begin Phase II clinical evaluation in the next few months. We also acknowledge that a group of world-leading experts have agreed to discuss the future development of aganirsen during the current ARVO conference. Their insight is invaluable and gratefully accepted by our team." Aganirsen (topical emulsion) was applied daily in non-human primates following laser-induced choroidal neovascularization (CNV), a model of wet age-related macular degeneration (AMD). Retinal aganirsen concentrations were assessed in monkeys following topical delivery (21.5, 43, or 86 g). Aganirsen was found to dose-dependently inhibit neovascular lesion development, with the incidence of high-grade CNV lesions (grade IV, as measured by fluorescein signal intensity) decreasing from 20.5% in vehicle-treated animals to 1.7% (p<0.05) in animals treated with the highest dose of Aganirsen (86 µg/day). The size of neovascularization complexes was also significantly lower in eyes receiving high dose and low dose aganirsen (p<0.0001) compared with vehicle-treated eyes. [Press release]