Dr. Wilhelm Schwaeble is Professor of Immunology. His research focusses on the roles of the complement system in pathophysiology of diseases caused through an overreactive immune response and he developed immune therapeutic reagents targeting early activation events that initiate and maintain inflammatory disease.
He was born in Mainz, Germany, where he studied Medicine, Biology and Psychology supported by the “Studienstiftung” at the Johannes-Gutenberg-University receiving a PhD (summa cum laude) in 1988, followed by successfully conclusion of the habilitation procedure (Dr. rer.nat. habil.) before moving to England. He was promoted to a Personal Chair as Professor of Immunology at the University of Leicester in 2002, where he graduated with a Higher Doctorate, Doctor of Science, in 2007. His work has been generously funded by the WELLCOME TRUST, the MRC, the ROYAL SOCIETY, the NIHR, the DEUTSCHE FORSCHUNGSGEMEINSCHAFT, throughout his career. He is recipient of the DAIWA/ADRIAN Prize for Research Excellence in Anglo/Japanese Collaborations, the FRANK MAY Prize and the ROYAL SOCIETY WOLFSON RESEARCH MERIT AWARD. He published many highly cited research articles in field-leading Journals.
He has been a consultant for the Seattle-based Biotech company OMEROS CORPORATION with whom he developed and maintained a strong patent portfolio of over 600 patents through 20-year-long collaboration. Most recently he received generous support from the NIHR/MRC to analyse the molecular basis of events that initiate and maintain the moderate to severe inflammatory endothelial disease caused in some individuals infected with SARS-CoV-2, now known as COVID-19 as Principal Investigator of the Cambridge-based consortium “Humoral Immune Correlates of COVID-19”. He developed various novel therapeutic reagents (out of more than 600 patents in his name) that modulate complement activation for each of the three complement activation pathways.
His most recent commercial successes were:
- The FDA-approval in Dec. 2025 to bring the only licensed therapeutic to treat Stem-Cell-Transplant-Associated-Microangiopathy, a drug named YARTEMLEA, originally invented by him and developed and marketed by OMEROS, into the Clinic;
- A 2.1 billion dollar investment from Novo Nordisk to partner with OMEROS Corporation/Seattle, to finalise Clinical Stage 2 and 3 Trials for FDA / EMA approval of another anti-inflammatory drug resulting from his inventions, now called ZALTENIBART, to treat Paroxysmal Noctural Haemoglobinurea.
In addition, Prof. Schwaeble has developed (in collaboration with his Cambridge co-worker Dr. Youssif Mohammed Ali and the OMEROS-based team of Dr. Munehisa Yabuki) a novel technology to generate desperately needed Pathogen-Specific-Clinical-Therapeutics, now known as T-CAT technology, to treat infectious diseases, work that is about to be published in SCIENCE TM. This new pipeline crystallised a lot of exciting novel opportunities in both Science and Drug Development. A sketch summarizing this new technology is shown as Figure 1.:
Fig.1. T-CAT mAb binds to the target microbial surfaces, activates complement and promotes pathogen elimination. (A) The biological events involved in T-CAT mediated pathogen elimination and the hypothetical neutralization of bacterial toxins. (B) Schematic presentation showing the structure of a T-CAT mAb furnished with a truncated form of human C1s. (CCP-I-CCP-II-SP domains) were fused to the heavy chains of the respective bacterial surface antigen-targeting mAbs. Adding a recombinant truncated C1s peptide to the C-terminus of the constant antibody domains adds enzymatic activity to the antibodies, which allows the T-CAT construct to initiate complement activation by directly cleaving plasma C4 and C4b-bound C2, leading to the formation of a CP-C3 convertase (C4bC2a), which in turn promotes the deposition of C3b on the bacterial surface. Accumulation of several C3b molecules in close proximity of the CP-C3 convertase switches the substrate specificity to C5, forming the C5 cleaving C4bC2a(C3b)n complex. C3b and iC3b opsonisation enhances uptake by C3-receptor bearing phagocytes and allows the formation of CP C5 convertases and AP C3 and C5 convertases. C5b deposits on the bacterial surface initiate the assembly of the membrane attack complex (MAC), resulting in bacterial lysis on susceptible bacterial pathogen surfaces. Complement activation appears to neutralise and eliminate the effects of bacteriotoxins released from invading pathogens.
