NOX-A12 (olaptesed pegol) is currently under development as a combination therapy in multiple oncology indications. The company recently reported top-line data from its Phase 1/2 combination trial in metastatic pancreatic and colorectal cancer together with MSD’s KEYTRUDA®.
NOXXON initiated a second combination trial of NOX-A12 with radiotherapy for clinical treatment of brain cancer (glioblastoma/glioma). NOX-A12 has received orphan drug designation for glioblastoma in the United States and glioma in Europe.
Mechanisms of action
NOX-A12 targets CXCL12 (C-X-C Chemokine Ligand 12), a key chemokine (signaling) protein. In cancer, it acts as a communication bridge or sign post between tumor cells and their environment, promoting tumor proliferation, new blood vessel formation and metastasis and reduces tumor apoptosis (cell death) (Source: Guo et al., 2015). NOX-A12 binds to two key sites in chemokine proteins to disrupt their activity and target them for destruction.
NOX-A12 is designed to fight solid tumors by modulating the tumor microenvironment in two distinct ways:
- Break tumor protection enabling active immune cells, T-cells, to enter the tumor with the aim of unleashing the full potential of immuno-oncology approaches, such as immune checkpoint inhibitors*
- Block tumor repair: through preventing the attraction of ‘repair cells’ to the tumors obstructing tumor re-growth following radiotherapy
*Fearon, D. T. (2014). "The carcinoma-associated fibroblast expressing fibroblast activation protein and escape from immune surveillance." Cancer Immunol Res 2(3): 187-193.
Presentation of the final clinical results from the Phase 1/2 study with CXCL12 inhibitor, NOX-A12, and pembrolizumab in patients with microsatellite-stable, metastatic colorectal or pancreatic cancer at the European Society for Medical Oncology (ESMO) Virtual Congress 2020.
Presented by: Dr. Niels Halama
Head of Department of Translational Immunotherapy at the German Cancer Research Center (DKFZ), Heidelberg
Medical Oncologist at the National Centre for Tumor Diseases (NCT), Heidelberg