NOXXON Pharma AG's NOX-A12 Delays Glioblastoma Recurrence in Preclinical Model
Published: Apr 04, 2012
The study, conducted in collaboration with the Stanford University School of Medicine, investigated the efficacy of NOX-A12 on brain tumor recurrences following irradiation in an animal model. In this model rats begin to die of brain tumors from approximately 120 days of age. These rats were treated with a single dose of whole brain irradiation (20 Gy) which was immediately followed by two different doses of NOX-A12 injected subcutaneously for either 4 or 8 weeks. Neither radiation nor NOX-A12 alone significantly affected the lifespan of the tumor-bearing rats; however the combination of the NOX-A12 (high or low dose) for 8 weeks and irradiation resulted in a significantly prolonged lifespan with the higher dose increasing median lifespan from 189 days for controls to 349 days (P value <0.0001)
NOX-A12 doses and treatment times in this preclinical study were chosen based on equivalents found to be safe and well tolerated in humans. Based on the results obtained from this study, the researchers believe that a clinical trial of NOX-A12 in combination with standard therapy in first-line glioblastoma patients would be justified at this point.
The abstract of this poster is available at the AACR Annual Meeting 2012 website: Link
About NOXXON Pharma AG
NOXXON Pharma is a biopharmaceutical company pioneering the development of a new class of proprietary therapeutics called Spiegelmers, a chemically synthesized, non-immunogenic alternative to antibodies. NOXXON has a diversified portfolio of clinical stage Spiegelmer®therapeutics:
- NOX-E36 targets the pro-inflammatory chemokine MCP-1 (CCL2) and is currently completing a Phase Ib study in healthy subjects and diabetics as well as a renal impairment study. A Phase II study in diabetics with renal impairment is planned to begin in April 2012.
- NOX-A12 targets SDF-1 (CXCL12), a chemokine mediator of tumor invasion, metastasis and resistance to chemotherapy, has completed Phase I. Phase IIa studies in two hematological cancers, multiple myeloma and chronic lymphocytic leukemia will begin in April 2012.
- NOX-H94 targets hepcidin, the key regulator of iron metabolism and mediator of iron restriction in anemia of chronic disease, and is currently in a comprehensive single and multiple ascending dose Phase I study. An endotoxin challenge study, designed to test the ability of NOX-H94 to block hepcidin mediated hypoferremia is currently running and a Phase II of NOX-H94 in myeloma or lymphoma patients with anemia is planned to start mid-2012.
The Spiegelmer® platform provides the company with powerful and unique discovery capabilities, which have generated a number of additional leads under preclinical investigation. Located in Berlin, Germany, NOXXON is a well-financed mature biotech company with a strong syndicate of international investors, approx. 60 employees and a highly experienced management team.
For more information, please visit: www.noxxon.com
NOX-A12 specifically antagonizes stromal cell-derived factor-1 (SDF-1 or CXCL12), a chemokine which attracts and activates immune- and non-immune cells. SDF-1 binds with high affinity to the chemokine receptors CXCR4 and CXCR7. The SDF-1 / CXCR4 / CXCR7 axis has been shown to play a role in stem cell as well as leukemic cell mobilization and homing, vasculogenesis, tumor growth, transendothelial migration, invasion and metastasis. Inhibition of the SDF-1 binding to its receptors sensitizes tumor cells to chemotherapy and in some solid tumors prevents invasion and metastasis, suggesting that NOX-A12 in combination with chemotherapy could be beneficial in the treatment of various cancers.
NOX-A12 has shown promising activity in models of stem cell mobilization and both hematological and solid tumors. In Phase I studies with healthy volunteers, single doses of NOXXON's SDF-1 inhibitor, NOX-A12, up to 10.8 mg/kg and daily doses up to 2 mg/kg for five days were found to be safe and well tolerated and resulted in dose-dependent mobilization of white blood cells and CD34+ cells as predicted by preclinical studies.
NOXXON received grant support within the program ”KMU-innovativ” from the German Federal Ministry of Education and Research (BMBF) for the preclinical program and the Phase I clinical trials with NOX-A12.
Further information about the planned clinical trials in multiple myeloma and chronic lymphocytic leukemia is available at ClinicalTrials.gov (IDs: NCT01521533 and NCT01486797).
NOXXON Pharma AG
College Hill Life Sciences
Dr. Robert Mayer
T: +49 (0)89 57001806