A novel therapeutic from Nextcure, Inc. has shown promise for the treatment of COPD by targeting VSTM-1 — a cell-surface inhibitory receptor highly expressed on granulocytes, including neutrophils and pulmonary monocytes — which functions as a regulator of myeloid cell-driven inflammatory cascades.
Inhibitory signaling is induced when VSTM-1 binds to ligands, such as cathelicidin and S100 proteins. This immunosuppressive function, combined with the strong expression profile of VSTM-1 on pulmonary myeloid cells and the prominent role of neutrophils as inflammatory mediators of lung immunotherapy, make VTSM-1 a promising novel therapeutic target for COPD.
NextCure has developed an agonist monoclonal antibody against VSTM-1 to modulate hyperinflammatory conditions, restore homeostasis and prevent disease. The agonist antibody has demonstrated activity in vitro, ex vivo and in highly relevant in vivo models. Key findings from the study include:
- The agonist antibody blocks neutrophil-mediated inflammation and cytokine production associated with tissue damage in vitro and ex vivo.
- Treatment with the agonist antibody reduces pulmonary pathology and prevents disease in animal models, including a highly relevant syngeneic mouse model engineered to express the human VSTM-1 protein.
“We have leveraged our immunology expertise and capabilities to continue expanding beyond oncology and into other diseases mediated by chronic inflammation,” said Solomon Langermann, PhD, NextCure’s chief scientific officer. “The VSTM-1 agonist mAb that we are advancing preclinically provides a differentiated approach with a unique mechanism to ameliorate pulmonary inflammation and the potential to treat and prevent chronic lung disease, including COPD. We believe we have a real opportunity to change the standard of care in COPD and other chronic inflammatory diseases, and address a key unmet need.”
The company said additional preclinical chronic models of inflammatory disease and relevant, mechanistically-based combination studies in COPD and other indications are planned.
