Pre-clinical & Discovery Programs
In addition to zilucoplan and the Ra Pharmaceuticals collaboration with Merck, the Company has discovery and pre-clinical programs targeting selective inhibition of other complement factors, including an oral, small molecule C5 inhibitor, Factor D and other complement inhibitors for certain renal, autoimmune, CNS diseases.
Factor D Inhibitor
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 Pharmaceuticals 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.
Oral C5 Inhibitor
This screening campaign has led to the identification of small molecules that bind to C5 at this site, inhibit cleavage, and inhibit red blood cell lysis in an in vitro assay. Small molecules and peptides that bind to other sites on C5 have yielded information on new mechanisms for C5 inhibition that are expected to contribute to a pipeline of highly differentiated, orally-available products.
Ra Pharmaceuticals is using this platform technology to generate cyclic peptides that bind C1s and inhibit the protease activity of C1s, C4b production, and red blood cell lysis in an in vitro assay. The Company expects C1s inhibitors to have broad utility in a number of disease areas.