A Novel Full-Length Recombinant Human Complement Factor H (CFH; GEM103) for the Treatment of Age-Related Macular Degeneration Shows Similar Functional Activity to Native CFH.

PURPOSE

GEM103 is a recombinantly produced full-length version of the human complement factor H (CFH) under clinical investigation for treatment of age-related macular degeneration (AMD) in individuals carrying an AMD risk-associated genetic variant of . This study aimed to investigate the complement pathway-related functions of GEM103 in comparison with those of native human CFH.

METHODS

Key biological activities of GEM103 and human serum-derived CFH (sdCFH) were compared using four independent functional assays. Assays of C3b binding and C3 convertase decay-accelerating activity (DAA) were performed by surface plasmon resonance (SPR). Cofactor activity (CA) was measured using 8-anilinonaphthalene-1-sulfonic acid as a fluorescent probe of C3b integrity. The abilities of GEM103 and sdCFH to protect sheep erythrocytes from hemolysis by CFH-depleted normal human serum were assessed colorimetrically.

RESULTS

In multiple SPR-based assays of C3b binding and DAA, the performance of GEM103 was consistently comparable to that of sdCFH across a range of matching concentrations. The EC ± SD in the fluorescence-based fluid-phase CA assay was 0.21 ± 0.06 µM for GEM103 compared to 0.20 ± 0.09 µM for sdCFH. In hemolysis assays, the EC value of 0.33 ± 0.16 µM for GEM103 versus 0.46 ± 0.06 µM for sdCFH were not significantly different ( = 0.81).

CONCLUSIONS

GEM103, a recombinant CFH developed by Gemini Therapeutics, shows activity profiles comparable to sdCFH in all complement-related assays employed in this study, suggesting that GEM103 is equivalent to the native glycoprotein in terms of its functional activity. These results support further study of GEM103 as a potential therapy for AMD.