The complement system is a humoral defence system that contributes to inflammatory tissue damage in various human diseases, in particular antibody-mediated diseases and in ischemia-reperfusion conditions. Among diseases that can be treated with PRO-02 are autoimmune haemolytic anaemia (prevalence 15-17/100.000) and chronic inflammatory demyelinating polyneuropathy (prevalence 8-10/100.000). However, for proof of concept in humans, PRO-02 is planned to be developed first for antibody-mediated rejection of kidney allografts (AMR) because of the unmet medical need and the availability of a validated ex-vivo model.
The complement system consists of more than 30 proteins most of which circulate as inactive (precursor) molecules. In the presence of a complement activator, the complement system becomes activated. This activation process resembles a domino game in which one activated component activates the next one, which in its turn actives the third one and so on finally resulting in cytotoxicity by the formation of the membrane attack complex (MAP).
PRO-02 is a monoclonal antibody (mAb) that interferes with complement activation and prevents its cytotoxic effects. PRO-02 differs from Soliris (anti-C5 mAb) in that it targets a different complement component.
Complement plays a major role in so-called ischemia reperfusion injury, which is the tissue damage occurring upon reperfusion of ischemic tissues. Hence, PRO-02 can also be used for the treatment or prevention of ischemia-reperfusion conditions such as Delayed Graft Function after kidney transplantation, acute myocardial infarction and stroke.
A lead murine mAb has been identified, humanized and de-immunized (PRO-02). Manufacturing cell-lines (CHO) of PRO-02 have been generated. PRO-02 dose dependently inhibits complement dependent cytotoxicity of human cells sensitized with anti-HLA antibodies (ex vivo proof of concept). A biochemical proof of concept and toxicity study in non-human primates has been finalized with favourable results and no signs of toxicity.