hematology

NOXXON´s second clinical candidate specifically antagonizes stromal cell-derived factor-1 (SDF-1), a chemokine which is a key regulatory element in the homing and retention of hematopoietic stem cells in the bone marrow. SDF-1 binds with high affinity to the chemokine receptors CXCR4 and CXCR7. The CXCR4/SDF-1 axis has been shown to play a role in stem cell mobilization, vasculogenesis, tumor growth and metastasis.

NOX-A12 has been evaluated in models of stem cell mobilization, angiogenesis, inflammation and lung and kidney injury. In these models NOX-A12 reduced pathological angiogenesis and tissue remodeling. In preclinical safety and two weeks toxicology studies NOX-A12 was safe and did not show any organ toxicity. In particular NOX-A12 did not exert any immunotoxicity effects, such as Toll-like receptor activation or changes in cytokine levels.

The first-in-human clinical trial for NOX-A12 has been successfully completed in May 2010. This Phase I study was designed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy individuals following intravenous administration of the stromal cell-derived factor factor-1 (SDF-1) antagonizing Spiegelmer® NOX-A12. Final data analysis demonstrated an excellent safety and tolerability up to the highest tested dose of 10.8 mg/kg NOX-A12/kg body weight. In addition, analysis by flow cytometry revealed a long lasting and dose dependent mobilization of WBC and CD34 positive cells.

NOXXON plans to start a multiple dose Phase I clinical trial by the mid of 2010. The Phase II program will commence late in 2010.

Spiegelmer NOX-H94 is NOXXON’s preclinical candidate for the treatment of anemia of inflammation, a common form of anemia associated with many chronic diseases. This Spiegelmer binds an innovative target centrally involved in iron homeostasis. NOX-H94 is currently undergoing final pre-clinical profiling.