NOX-A12 (olaptesed pegol) is a Spiegelmer* drug candidate under development as a combination therapy in multiple oncology indications. This compound has shown what we believe to be strong results in pre-clinical and clinical studies including in two Phase 2a trials. NOXXON is convinced the future of cancer therapy will be based on combination therapy and is aiming to develop the must-have combination partner.
NOXXON intends to develop NOX-A12 in advanced solid tumors such as colorectal and pancreatic cancer, brain cancer and multiple myeloma. NOX-A12 has received orphan drug designation for glioblastoma in the United States and glioma in Europe.
The unmet medical need in certain solid tumors is very high. When the cancer is not detected before it spreads outside of the location in which it arises, this greatly increases the risk for patients that treatment will not be successful. The five-year survival statistics for solid cancers (Source: U.S. National Cancer Institute's SEER database, accessed September 2015) highlight this medical need. The five-year survival for patients with lung cancer is 17.4% and with pancreatic cancer is 7.2%. For colorectal cancer that has metastasized, or spread, the five-year survival rate of patients is 13.1%. As such, there is a clear need for better treatments for these patient groups.
NOXXON estimates annual eligible patient population for NOX-A12 in lung cancer to be approximately 238,000 and in colorectal cancer approximately 96,000 patients in the United States and Europe (Germany, France, Italy, Spain and United Kingdom):
Mechanisms of action
NOX-A12 targets CXCL12 (C-X-C Chemokine Ligand 12), a key chemokine (signalling) protein, which promotes tumor proliferation, new blood vessel formation and metastasis and reduces tumor apoptosis (cell death). NOX-A12 exploits the ability of Spiegelmers to bind to two key sites in chemokine proteins to disrupt their activity and target them for destruction.
NOX-A12 is designed to fight tumors by modulating the tumor microenvironment in three distinct ways:
- Expose hidden tumor cells. CXCL12 attracts blood cancer cells to protective niches in the bone marrow. NOX-A12 is intended to expel tumor cells from these niches leaving cancer cells in the blood stream where tumor killing drugs are more effective
- Break tumor protection. CXCL12 forms a protective biochemical 'wall' around certain solid tumors, blocking entry of immune system cells that can kill tumor cells. NOX-A12 has the potential to destroy the 'wall', 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. CXCL12 attracts ‘repair cells’ to tumors damaged by anti-cancer therapy, for instance following radiotherapy. NOX-A12 is aimed at blocking this effect so that the tumor is less able to re-grow
*Fearon, D. T. (2014). "The carcinoma-associated fibroblast expressing fibroblast activation protein and escape from immune surveillance." Cancer Immunol Res 2(3): 187-193.
About the target
Stromal cell-derived factor-1 (SDF-1/CXCL 12) is a chemokine that is normally involved in cell migration and plays a key role in the tumor microenvironment. CXCL 12 is secreted by supporting cells in the bone marrow and lymph nodes which maintains blood-forming stem cells and white blood cells in these tissues. Like other chemokines, CXCL 12 has two types of binding sites both of which are important in its role in the tumor microenvironment and have implications for therapeutic intervention. One of these sites in CXCL 12/SDF-1 binds with high affinity to the chemokine receptors CXCR4 and CXCR7. The other site acts as a non-specific anchor that allows the chemokine to act like a signpost fixed on the surface of cells.