The complement immune system consists of more than 30 plasma proteins and cellular components that interact in proteolytic cascades for an efficient and rapid activation in response to infection, leading to inflammation, opsonization, and targeted cytolysis. When appropriately activated, these pathways play an important role in maintaining normal ocular health.
The complement system can be activated by three different pathways: the classical pathway, the lectin pathway, and the alternative pathway. The alternative pathway is constantly activated and is highly regulated on host cells to limit damage while being amplified on non-host cell to provide protection from pathogens and unwanted cells. Complement factor H (CFH) is a major regulator of the alternative complement cascade.
Immunohistochemical analyses have shown that a large number of complement components, including complement factor H (CFH), are molecular constituents of drusen, a type of cell debris which is a clinical hallmark of dry AMD. Continuous control the alternative pathway by CFH is necessary due the amplifying properties of the alternative pathway and its potential to provoke unneeded inflammatory response if not properly controlled. This control is best achieved by maintaining regulatory function of the complement system, e.g. by augmenting CFH activity and thereby inhibiting detrimental effects of the overly active complement system while keeping the beneficial aspects such as cell debris clearance intact.
Gemini is restoring regulation of the complement pathway, a unique approach to addressing over-activation of the innate immune system in diseases such as dry AMD and linked diseases.
Based on the biological activity of CFH, Gemini is developing a recombinant CFH protein, GEM103, for the treatment of dry AMD. As a regulatory protein, GEM103 is expected to restore appropriate complement regulation by blocking the detrimental effects (e.g., inappropriate cell lysis and exaggerated immune responses) while retaining the beneficial effects (e.g., clearance of extracellular debris, repair of oxidative damage) of complement pathway activation. 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.
GEM103
Gemini is developing a recombinant CFH protein, GEM103, for the treatment of dry AMD. As a regulatory protein, GEM103 is expected to restore appropriate complement regulation by blocking the detrimental effects (e.g., inappropriate cell lysis and exaggerated immune responses) and retaining the beneficial effects (e.g., clearance of extracellular debris, repair of oxidative damage) of complement pathway activation. This mechanism of action is in contrast to that of complement pathway inhibitors which block both the detrimental and beneficial effects of complement activation.