Disease Targets

Wet AMD

Age-related macular degeneration (AMD) is the leading cause of visual loss in the western world. This disease of the aging eye results in loss of the sharp, central vision that is necessary for clearly seeing objects and undertaking routine tasks including reading and driving. AMD occurs in both wet and dry forms, with the wet form accounting for the vast majority of cases of AMD-related blindness and progressing much more rapidly than dry.

Wet AMD is a highly-complex disease caused by a number of molecular and cellular factors tied not only to angiogenesis, but also inflammation, fibrosis, and blood vessel permeability, among others. The disease typically manifests itself through the development of new, very fragile blood vessels (neovascularization) that will often leak blood and fluid under the macula. The result is rapid damage to the macula that can cause the loss of central vision in a short period of time.

Typically striking individuals in their mid-70s but seen in patients as early as age 50, wet AMD can cause permanent blindness. The aging of the baby boomer population, along with several other demographic factors, is contributing to a dramatic increase in the number of Americans experiencing wet AMD.

It is presently estimated that wet AMD affects approximately two million Americans. Growing at an annual rate of approximately 13%, it is expected that the total number of patients will exceed 3.5 million by 2010. Industry experts expect the total U.S. market opportunity for wet AMD therapeutics to reach close to $2 billion by that time. This does not include the potential market for a compound designed to prevent wet AMD. Such a market would be substantially larger than this estimate.

MacuSight is presently advancing sirolimus for both treatment and prevention of wet AMD.

Wet AMD Treatment

Sirolimus is able to broadly address many of the underlying etiological factors believed to be responsible for the development of wet AMD, positioning the compound as a potentially superior option for disease treatment and prevention. This is largely attributable to sirolimus' potential ability to inhibit and regress choroidal neovascularization (CNV) associated with wet AMD. Furthermore, sirolimus impacts the mammalian target of rapamycin (mTOR), which plays a critical role in regulating basic cellular functions including cell proliferation, survival, mobility and angiogenesis. As such, inhibitors of mTOR are expected to show a therapeutic effect in treating the pathological angiogenesis of CNV associated with wet AMD.

MacuSight recently announced preliminary results from a prospective Phase 1 study of sirolimus in 30 patients with wet AMD. Data demonstrated that MacuSight's proprietary formulation of sirolimus was safe and well-tolerated in all doses tested with two different routes of administration (subconjunctival injection and intravitreal injection). The trial showed no evidence of increased intraocular pressure, inflammatory response to treatment, or indication of progression of cataracts.

Furthermore, the study provided an initial assessment of sirolimus' biological activity in AMD with patients demonstrating improvements in visual acuity despite extended duration of disease prior to entering the study. Additionally, patients also experienced anatomical improvements as demonstrated by reductions in retinal thickness. These preliminary findings demonstrated that sirolimus administered via subconjunctival injections was as effective, if not more so, than sirolimus administered via intravitreal injections.

MacuSight intends to complete its collection and analysis of all data from this trial and present final findings at the Retinal Physician Symposium in Naples, Florida in May 2008. The company is also initiating a Phase 2 clinical trial in wet AMD.

Wet AMD Prevention

While dry AMD can cause blindness on its own, more often it is the conversion to wet AMD that leads to significant visual loss. Today's wet AMD therapeutics are only able to treat established cases of the disease, and importantly, once wet AMD is diagnosed, it is often not possible to improve patients' vision. For these reasons, the prevention of wet AMD remains a significant unmet medical need and an even larger market opportunity. MacuSight believes that the coupling of sirolimus' broad activity with proprietary minimally-invasive, sustained delivery potentially positions its product as the first for the prevention of wet AMD.

"Industry experts expect the total U.S. market opportunity for wet AMD therapeutics to reach close to $2 billion by 2010."