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NOXXON's SDF-1 inhibitor NOX-A12 completes Phase I
Preclinical data in models of hematological tumors to be presented at ASH conference(PresseBox) ( Berlin, )
NOX-A12 pre-clinical results in hematological malignancies will be presented in a talk at the annual meeting of the American Society of Hematology (ASH) in San Diego, USA from 10-13 December 2011. Members of NOXXON's drug development team and collaboration partners will be at the ASH conference to explain the mode of action and clinical potential of this innovative drug candidate.
The titles and contributors to the three NOX-A12 presentations at ASH are as follows:
- Oral presentation Monday, December 12, 7:15 PM; Session 652; Room 6A
L-Stereoisomer RNA Oligonucleotide Anti-SDF-1 (NOX-A12) Disrupts the Interaction of Multiple Myeloma Cells with the Bone Marrow Milieu In Vivo, Leading to Enhanced Sensitivity to Bortezomib
A. M. Roccaro, A. Sacco, P. Qaung, A. Azab, P. Maiso, F. Azab, Y. Zhang, G. C. Issa, Y. Liu, H. T. Ngo, A. Kruschinski, I. M. Ghobrial
- Poster presentation Sunday, December 11, 6:00 PM-8:00 PM; Session 711; Poster II in Hall GH
Rapid and Efficient Mobilization of Murine Hematopoietic Stem and Progenitor Cells with NOX-A12, a New Spiegelmers-Based CXCR4/SDF-1(CXCL12) Antagonist
M. Scheller, F. Schwoebel, D. Vossmeyer, A. Leutz
- Poster presentation Monday, December 12, 6:00 PM-8:00 PM; Session 641; Poster III in Hall GH
The Spiegelmer NOX-A12, a novel SDF-1 (CXCL12) inhibitor, and its effects on Chronic Lymphocytic Leukemia (CLL) cell migration.
J. Hoellenriegel, D. Zboralski, Z. Estrov, W. G. Wierda, M. Keating, A. Kruschinski, J. A. Burger
Based on compelling pre-clinical data in hematological and solid tumors, NOXXON believes that NOX-A12 has the potential to be developed for treatment of multiple oncology indications. Initiation of the first Phase IIa trial of NOX-A12 in a hematological tumor indication is planned early in 2012, subject to regulatory and ethics committee approvals.
NOX-A12 specifically antagonizes stromal cell-derived factor-1 (SDF-1), 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 mobilization, vasculogenesis, tumor growth 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 trial in relapsed CLL patients is available at ClinicalTrials.gov (ID: NCT01486797).
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