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 first priority is to develop NOX-A12 in advanced solid tumors such as colorectal and pancreatic cancer which do not usually respond to checkpoint inhibition as monotherapy. Other indications where NOXXON has developed plans for clinical development include brain cancer (glioblastoma/glioma)and multiple myeloma. 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 (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:

  • Solid tumors pancreatic and colorectal cancer: 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*
  • Brain cancer/glioblastoma: 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 to block tumor re-growth
  • Blood cancers like MM: 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

    *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
NOX-A12 targets a key chemokine in the TME, CXCL12, also known as stromal cell-derived factor-1 (SDF-1), that is naturally involved in the migration of blood cells and in cancer acts as a communication bridge between tumor cells and their environment (Source: Guo et al., 2015). While CXCL12 and other chemokines generally attract cells , it is now understood that under certain conditions of very high local concentrations, CXCL12 can act as a repulsive factor for cytotoxic or killer T-cells, which are key cells of the immune system (Source: Poznansky et al., 2000 & Lee et al., 2009).

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 on migrating cells, which is how they “see” CXCL12. The other site acts as a non-specific anchor that allows the chemokine to act like a signpost fixed on the surface of cells, for example, on a blood vessel wall.

Details of clinical studies available at clinicaltrials.gov
  • NOX-A12 First-in-human (FIH) Study
    (ref: NCT00976378)
    Status: completed
  • NOX-A12 Multiple Ascending Dose Study in Healthy Volunteers
    (ref: NCT01194934)
    Status: completed
  • NOX-A12 in Combination With Bendamustine and Rituximab in Relapsed CLL
    (ref: NCT01486797)
    Status: ongoing
  • NOX-A12 in Combination With Bortezomib and Dexamethasone in Relapsed Multiple Myeloma
    (ref: NCT01521533)
    Status: ongoing
NOX-A12 publication archive
NOX-A12 press release archive

The press releases contained in this archive section are provided for historical purposes only. The information contained in each press release is accurate only as of the date each press release was originally issued. NOXXON disavows any obligation to update the information contained in such press releases after the date of their issuance.