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):

Sources: GloboCan 2012 data (accessed August 2015), DrugAnalyst - (accessed August 2015) and company annual reports.

Glioblastoma is a particularly aggressive type of brain cancer in which tumor cells invade surrounding tissue, rendering surgical treatment and chemotherapy less effective (Source: Mrugala, M. Discovery medicine 15.83, 2013). The annual number of new cases of glioblastoma is estimated at 26,000 in the United States and the five major European countries (Germany, France, Italy, Spain and United Kingdom) with the median five-year survival rate for patients with glioblastoma of less than 10% (Source: American Brain Tumor Association, accessed August 2015).

MM is the second most common blood cancer with an estimated number of 19,600 new cases each year and a total five-year prevalence of 46,000 patients in the United States and 24,400 new cases each year and a total five-year prevalence of 56,800 patients in the five major countries in Europe (Germany, France, Italy, Spain and United Kingdom) (Source: GloboCan data, accessed August 2015). This blood cancer is characterized by the over-production and accumulation of monoclonal plasma cells, a type of white blood cell normally responsible for producing antibodies in the bone marrow. It is now understood that in the disease process of MM, the mechanisms responsible for the interaction between cancer cells and their microenvironment are as important as the genetic changes involved in the development of the cancer cells themselves. Such genetic changes play an important role in bone destruction, tumor cell growth, survival, migration and drug resistance (Source: San Miguel, 2014).

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.

Details of clinical studies available at
  • 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.