NOX-A12 (olaptesed pegol) is currently under development as a combination therapy in multiple oncology indications and is one of the few agents that we believe offers the potential to address the major unmet need in pancreatic cancer and glioblastoma. The company recently reported final top-line data that warrant further development from its Phase 1/2 combination trial in metastatic pancreatic and colorectal cancer together with MSD’s KEYTRUDA®.
NOX-A12 has received orphan drug designation for glioblastoma in the United States and glioma in Europe. NOXXON’s ongoing clinical study of NOX-A12 combined with radiotherapy for clinical treatment of newly diagnosed brain cancer patients who would not benefit from standard chemotherapy has reported preliminary data in Oct 2020 showing consistent tumor reductions and no unexpected adverse events.
Mechanism of action
NOX-A12 targets CXCL12 (C-X-C Chemokine Ligand 12), a key chemokine (signaling) protein. Chemokines can be thought of as road signs in the body that direct movement of cells that encounter them. Like road signs, chemokines are anchored in place (location information) and contain directions, such as “do not enter”, for cells that can “see” them with the appropriate receptors. In cancer, CXCL12 acts as a communication bridge 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 anti-cancer immune cells, such as killer 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