Complement Factor I (CFI) is a critical regulator of all complement pathways through its ability to degrade activated complement proteins C3b and C4b to their inactive form in the presence of cofactors. CFI is constitutively expressed by the retinal pigment epithelium (RPE), the site of drusen formation in AMD. Biomarker data from ocular fluid indicates local complement dysregulation/undesirable degree of complement activation in AMD patients. Polymorphism in gene encoding of this important negative regulator of the complement pathway, CFI, is associated with the risk for AMD and linked diseases. Recent reports show that rare, highly penetrant CFI variants that reduce the expression and secretion of CFI can contribute to a much greater risk of AMD and linked diseases. The implication of these findings is that a balance must be reached between activation and regulation in clearing debris to avoid collateral tissue damage in the retina. This can be best achieved by restoring regulatory function of the complement system, for example by augmenting CFI activity.
Gemini is aiming to restore regulation of the complement pathway using recombinant CFI to address dysregulation/overactivation of the innate immune system in diseases such as dry AMD and linked diseases.
Based on the biological activity of CFI, Gemini is developing a recombinant CFI protein, GEM104, for the treatment of dry AMD. As a regulatory protein, GEM104 is expected to restore appropriate complement regulation by degrading activated complement proteins C3b and C4b to their inactive form. This hypothesized mechanism of action is in contrast to that of complement pathway inhibitors, which constrain both the detrimental and beneficial effects of complement activation.