The complement system shares many similarities with the hemostatic system. They both function as cascades of enzymes. Whereas the hemostatic system is central to stopping bleeding, the complement system plays a central role in both innate and adaptive immune responses. The resultant process helps to attract certain immune system cells at the site of infection or inflammation, to eliminate pathogens, and to mediate various specific responses to foreign proteins through effects on the immune system. When the complement system is over-reactive, it can cause severe diseases.
Thus, drugs that target the complement cascade could potentially be beneficial in a variety of indications, including but not limited to dry AMD, atypical hemolytic uremic syndrome (aHUS), paroxysmal nocturnal hemoglobinuria (PNH), complement 3 glomerulopathy (C3G) as well as neurological disorders, such as myasthenia gravis. Common to these diseases are that they are relatively rare and severely debilitating or life-threatening, for which large unmet medical needs still exist. Many key targets, such as the complement proteins C3 and C5, within the complement cascade circulate in high concentrations such that it can be difficult or impractical to block their action using antibody-based or small molecule approaches.
We believe that targeting complement proteins using engineered enzymes is an efficient way to overcome some of the challenges of inhibiting the complement cascade. In contrast to an antibody or small molecule where one therapeutic compound neutralizes one target, a single protease has the potential to neutralize thousands of target complement molecules. Preclinical support for using this design strategy to target the complement pathway was presented at the 2019 Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO) in the spring of 2019 highlighting our preclinical anti-C3 candidate being developed for the treatment of geographic atrophy (GA) associated dry AMD.
SQ Systemic complement inhibitors
We have initiated discovery research to identify novel complement pathway regulating proteases.
We have developed CB 2782-PEG, which is a potent, long acting anti-C3 protease that selectively degrades C3 into inactive fragments. Our preclinical data predict best-in-class human intravitreal dosing three or four times a year. In December 2019, Catalyst Biosciences and Biogen entered into a global license and collaboration agreement for the development and commercialization of pegylated CB 2782 (CB 2782-PEG) for the potential treatment of geographic atrophy (GA) associated dry age-related macular degeneration (dry AMD). Under the terms of the agreement, Biogen has an exclusive worldwide license to develop and commercialize CB 2782-PEG and Catalyst’s other anti-C3 proteases for the potential treatment of dry AMD. Catalyst is performing pre-clinical and manufacturing activities and Biogen is solely responsible for funding the pre-clinical and manufacturing activities and performing Investigational New Drug (IND)-enabling activities, worldwide clinical development, and commercialization.