OT-551 for Geographic Atrophy / Dry AMD

(Currently in Phase 2 Clinical Trials)

Othera’s most advanced clinical-stage drug candidate, OT-551, is a proprietary small molecule, delivered topically by eye drop, with a novel mechanism of action. OT-551 is in development for Geographic Atrophy (GA), an advanced form of Dry Age-Related Macular Degeneration (AMD).

OT-551 is a potent free radical scavenger that also targets inflammatory pathways (e.g. NF-kB), and its unique physical and chemical properties allow it to readily penetrate cells and tissues throughout the eye, including the retina. As a result, OT-551 is potentially effective across a broad range of ophthalmic diseases where oxidative stress, angiogenesis and/or inflammation is involved, especially AMD, and GA in particular, where the breakdown of natural defenses in the eye over time is a key component of the disease mechanism.

In June 2007, Othera enrolled its first patient in the OMEGA Study, a multi-center phase 2 clinical trial to evaluate OT-551 eye drops in the treatment of GA. To learn more about this trial, or if you are interested in participating, please contact clinicaltrials@othera.com.

The National Eye Institute is also conducting a Phase 2 clinical trial to study OT-551 in dry AMD. Initiated in December 2006, this study is an open-label trial to evaluate the impact of OT-551 on disease progression in patients with bilateral (both eyes) Geographic Atrophy.

Age-Related Macular Degeneration (AMD)

AMD is an incurable, chronic degenerative eye disease affecting more than 15 million Americans. It is a leading cause of blindness for people age 55 and older. The National Eye Institute has called AMD a national epidemic and estimates that approximately 20 million people will be affected by 2020.

AMD is caused by deterioration of the central portion of the retina, specifically in an area inside the back of the eye known as the macula. The macula records the images we see and sends them via the optic nerve from the eye to the brain. The macula is responsible for focusing central vision in the eye and controls our ability to read, drive a car, recognize shapes or colors, and see objects in fine detail. AMD is typically classified as either the atrophic (dry) or neovascular (wet) form of the disease, although they can exist concurrently in the eye.

Dry AMD

The most common form of AMD is referred to as the atrophic or "dry" form of the disease. Of the 15 million people affected by AMD in the U.S., about 85-90% have dry AMD. There are no FDA-approved treatments for dry AMD, although studies have shown a modest effect of oral antioxidant vitamins in slowing the progression of AMD.

Dry AMD develops over many years, and one of the first clinical manifestations is the formation of yellow deposits, spots known as drusen, in the macula. With time, drusen tend to grow in both size and number, leading to late-stage AMD where the function of critical photoreceptor cells is compromised.

Geographic atrophy is an advanced form of dry AMD characterized by thinning and discoloration in the macula in defined lesions. These lesions are associated retinal pigment epithelial (RPE) cell death and the loss of overlaying photoreceptors. As these photoreceptors die, central vision begins to irreversibly decline. Depending upon the rate and severity of vision loss, patients can ultimately become legally blind.

OT-551 in Dry AMD

Preclinical evidence shows that OT-551 may be an effective treatment for dry AMD based on its multiple mechanisms, including through its anti-inflammatory and anti-oxidant activities. A study performed by Dr. Robert E. Anderson at the University of Oklahoma, presented at the 2006 ARVO Meeting and recently published in the journal Investigative Ophthalmology & Visual Science (IOVS), demonstrated that OT-551 can protect the retina against oxidative stress damage as commonly occurs in dry AMD. The following chart shows these findings: