Keratoconus (KCN) is a corneal disorder in which the central portion of the cornea becomes thinner and bulges forward in a cone-shaped fashion resulting in myopia, irregular astigmatism, and eventually visual impairment. The earliest signs of keratoconus are usually blurred vision and frequent changes in eye glass prescription, or vision that cannot be corrected with glasses. Symptoms of keratoconus generally begin in the late teenage years or early twenties, but can start at any time. Treatment options are surprisingly limited with no oral or topical pharmaceutical therapy. Most mild KCN can be corrected with glasses or soft contact lenses but very often patients will need toric or hard contacts as the disease progresses. Ultimately, 1 in 5 patients will require surgery, such as corneal transplant or UV-A crosslinking, which poses significant risks of scarring, visual haze, fluctuation, and pain. Our technology, IVMED-80 eye drops, is based on a co-factor for lysyl oxidase (LOX) activity. Deficient LOX activity in the cornea has been linked to the development of keratoconus both genetically and biochemically. Using Phase 1 funding support, we were able to restore lysyl oxidase activity in human corneal fibroblasts from keratoconic corneas and increase levels of crosslinked collagen as measured by lysylnorleucine in rabbit eyes. We demonstrated topical therapy increased biomechanical strength of human cadaver corneas and rabbit corneas as measured by both extensiometry ex vivo and waveform deformation analysis in vivo. Finally, topical copper therapy induced flattening of the rabbit cornea comparable to levels observed with conventional surgical crosslinking in humans. This body of data resulted in iVeena being granted orphan designation for IVMED- 80. In this Phase 2 SBIR project, we propose experiments that will enable us to submit an IND and start a US clinical trial. We propose to analyze optimal duration of therapy and potential risk of relapse after different durations of treatment, manufacture a GMP batch with stability testing according to ICH guidelines, and perform a 6-month GLP toxicology study in rabbits.

Public Health Relevance

Keratoconus is a progressive corneal thinning disorder that compromises vision, is usually bilateral, and is the leading cause of full-thickness corneal transplantation in the US. The most recent treatment for keratoconus, UV-A assisted surgical crosslinking, poses significant risks of infection, scarring, haze, visual fluctuation, and pain; there is no pharmacologic treatment as yet for this debilitating, vision-threatening disorder. iVeena is developing a new topical eyedrop therapy for keratoconus which works by enhancing physiological corneal crosslinking through increasing lysyl oxidase activity, without the need for light or surgery.

National Institute of Health (NIH)
National Eye Institute (NEI)
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
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Special Emphasis Panel (ZRG1)
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Lee, Paek-Gyu
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Iveena Delivery Systems, LLC
Salt Lake City
United States
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