Novel Therapeutics:
CATK Therapeutics: Blocking a Macrophage Protease to Prevent Vascular Collapse in Sepsis and Tissue Injury in IBD
Samir M. Parikh, M.D.
- Chief, Division of Nephrology
- Professor of Medicine
- Professor of Pharmacology
- Robert Tucker Hayes Distinguished Chair
- Ruth W. and Milton P. Levy, Sr. Chair in Molecular Nephrology (UT Southwestern Medical Center).
In sepsis, the immune system can accidentally “blow holes” in the microvasculature, causing fluid leak, shock, and organ failure. Dr Samir Parikh’s team discovered that macrophages release cathepsin K (CATK), a protease that cuts angiopoietin-2 into toxic fragments that shut down Tie2, the pathway that normally keeps vessels stable. In a 2025 JCI study, blocking CATK with a clinical-stage inhibitor improved survival in multiple mouse sepsis models, and septic patients showed the same harmful angiopoietin-2 fragments linked to worse outcomes. This Discovery Track will translate the mechanism into a first-in-class CATK-blocking antibody, initially for sepsis/ARDS/AKI, with an expansion path into chronic inflammatory disease such as IBD. The team already has the models, patient biorepositories, and biomarker readouts to rapidly select a lead biologic and advance toward IND-enabling development and early clinical testing.
