Therapies for complement disorders
The complement system is a vital pathway acting within the immune system. It comprises a group of proteins that recognize viral and bacterial patterns, trigger inflammation, and break up the pathogens. Excessive complement-induced inflammation, though, is associated with disease such as kidney conditions, dry AMD, and even severe cases of Covid-19. Most of these indications cannot be treated to date.
An early component in the cascade of complement action, factor H, protects the body’s own cells and regulates the inflammation process. Unrestrained inflammation due to insufficient factor H leads to fatal tissue damage. Current methods to avoid this rely on artificial antibodies that block the pathway altogether. However, this measure also stops the inactivation of pathogens and causes a significant risk of infection.
Conversely, supplemented factor H allows for regulated defence while preserving the integrity of the host cells. Factor H is a complex protein that is difficult to produce. Only moss has been able to yield human-like, high-quality factor H, thus being a key enabler for factor H as a treatment.
Eleva has developed three variants of factor H: a full-length recombinant factor H (FH), a shortened recombinant factor H (FHL), both acting as natural complement regulators, as well as a novel multi-level regulator, a fusion factor H protein (MFHR1).
Compleva FH/CPV-104: natural complement regulator
Compleva FH/CPV-104 for patients suffering from
C3 glomerulopathy (C3G)
In C3G, the complement component 3 (C3) accumulates in the filtration units of the kidney (glomeruli), leading to substantial damage and ultimately to end stage renal disease. A single administration of moss-made Compleva FH effectively reduces C3-deposition in mice kidneys.
Compleva FH is currently in the preclinical stage.
Compleva MFHR1/CPV-102: novel multi-level complement regulator
Compleva MFHR1 is a fusion protein that combines several binding sites from the original factor H. This allows it to target selected components in the two major complement pathways. As a result, the main inflammation components are kept in check and glomerular C3 deposition is reduced.
Compleva MFHR1 is in preclinical stages.
Compleva FHL/CPV-103: natural complement regulator
A natural splice variant of Factor H, Compleva FHL comprises all functional domains but is smaller in size. This could be beneficial in the treatment of dry AMD.
Compleva FHL is in research phase.