Emerging data indicate that complement and neutrophils contribute to the maladaptive immune response that fuels hyperinflammation and thrombotic microangiopathy, thereby increasing coronavirus 2019 (COVID-19) mortality. Here, we investigated how complement interacts with the platelet/neutrophil extracellular traps (NETs)/thrombin axis, using COVID-19 specimens, cell-based inhibition studies, and NET/human aortic endothelial cell (HAEC) […]
Selected Publications
Complement C3 vs C5 inhibition in severe COVID-19: early clinical findings reveal differential biological efficacy
Read about our new study comparing C3 inhibition with C5 blockade in COVID19: our early clinical findings offer important insight into the differential mechanistic basis of C3 & C5 inhibition and support a broader therapeutic profile of AMY101 in COVID-19. Abstract: Growing clinical evidence has implicated complement as a pivotal […]
The first case of COVID-19 treated with the complement C3 inhibitor AMY-101
Acute respiratory distress syndrome (ARDS) is a devastating clinical manifestation of COVID-19 pneumonia and is mainly based on an immune-driven pathology. Mounting evidence suggests that COVID-19 is fueled by a maladaptive host inflammatory response that involves excessive activation of innate immune pathways. While a “cytokine storm” involving IL-6 and other […]
Complement as a target in COVID-19?
There is an urgent need to develop effective therapies for COVID-19. Here, we discuss the potential of targeting the complement system in these patients……., the upstream positioning of C3 signalling in the innate immune cascade further argues for the broader anti-inflammatory potential of C3 blockade with agents such as AMY-101, […]
Prolonged intraocular residence and retinal tissue distribution of a fourth-generation compstatin-based C3 inhibitor in non-human primates
Here we report the intraocular distribution and pharmacokinetic profile of the fourth-generation compstatin analog, Cp40-KKK in cynomolgus monkeys following a single intravitreal injection. Using a sensitive surface plasmon resonance (SPR)-based competition assay and ELISA, we have quantified both the amount of inhibitor and the concentration of C3 retained in the […]
The renaissance of complement therapeutics
Ricklin D, Mastellos DC, Reis ES, Lambris JD. (2017). The renaissance of complement therapeutics. Nature Reviews. Nephrology 14: 26-47.
Method development and validation for the quantitation of the complement inhibitor Cp40 in human and cynomolgus monkey plasma by UPLC-ESI-MS
Highlights: This study describes the development and validation of an ultra-high performance liquid chromatography electrospray mass spectrometry method for the quantitation of Cp40 in human and non-human primate (NHP) plasma. A local dose of AMY-101 (0.1 mg/site) that is free of local irritation and effective when given once every 3 […]
Complement in cancer: untangling an intricate relationship
Highlights: This review summarizes our current understanding of complement-mediated effector functions in the tumour microenvironment, focusing on how complement activation can act as a negative or positive regulator of tumorigenesis. This review offers insight into clinical aspects, including the feasibility of using complement biomarkers for cancer diagnosis and the use […]
Safety and efficacy of the complement inhibitor AMY-101 in a natural model of periodontitis in non-human primates
Highlights: This study was undertaken to determine the local safety of increasing doses of the drug as well as its efficacy when given at a reduced frequency or after systemic administration. A local dose of AMY-101 (0.1 mg/site) that is free of local irritation and effective when given once every […]
Local endothelial complement activation reverses endothelial quiescence, enabling t-cell homing, and tumor control during t-cell immunotherapy
Highlights: This study shows that in the context of adoptive T cell therapy, antitumor T cells, delivered at high enough doses, can overcome the endothelial barrier and infiltrate tumors, a process that requires local production of C3, complement activation on tumor endothelium and release of C5a. C5a acts on endothelial […]