Factor D Inhibitor

Dry Age-Related Macular Degeneration/Geographic Atrophy

Age-Related Macular Degeneration (AMD) is the most common cause of blindness in older adults, and has an estimated worldwide prevalence of 8.7% among all individuals aged 45 to 85. Dry AMD comprises 90% of all AMD cases, and is characterized by deterioration of the retina associated with the appearance of small deposits of debris, called drusen, under the macula. In approximately 5% of dry AMD patients, the disease progresses to an advanced stage known as geographic atrophy (GA). It is estimated that approximately 970,000 individuals in the United States have GA.

The alternative pathway of the complement system is implicated in dry AMD by the presence of almost all alternative pathway complement components in drusen deposits.

Although several therapeutics targeting vascular endothelial growth factor, or VEGF, to block growth of abnormal blood vessels are approved to treat wet AMD, there are no approved therapies for dry AMD or GA.

Ra Pharma® is developing inhibitors of complement Factor D for intravitreal administration, designed to prevent or reduce progression of GA in patients with dry AMD, thereby potentially preventing further vision loss and preserving sight.

C3 Glomerulonephritis/Dense Deposit Disease

C3 Glomerulonephritis (C3GN) and Dense Deposit Disease (DDD) are closely-related but distinct alternative pathway complement-mediated diseases characterized by C3 deposition in the kidney, with absent or minimal immunoglobulin deposition. The combined prevalence of C3GN and DDD is 1-3 per million individuals, with an estimate of approximately 1,000 patients in the United States. The clinical features of C3GN and DDD include compromised renal function and high blood pressure.

There are no approved therapies for C3GN or DDD. Patients are usually treated with angiotensin converting enzyme inhibitors and angiotensin II receptor blockers to modulate proteinuria, and with nonspecific immunosuppressants, including corticosteroids, when kidney inflammation is present.

Ra Pharma is developing specific inhibitors of Factor D as targeted drug candidates for C3GN. By blocking the alternative pathway upstream of C3, the Company believes this mechanism may prevent C3 deposition and subsequent renal injury.