CXCR4 antagonist POL6326
POL6326 is a potent and selective antagonist of the chemokine receptor CXCR4. This reversible and competitive CXCR4 antagonist blocks the interaction with the ligand SDF-1 (stromal cell-derived factor 1) resulting in the mobilization of stem cells from the bone marrow into the circulating blood. This effect can be therapeutically used for stem cell transplantation where stem cells are collected from the blood by a procedure called apheresis and infused after chemotherapy to accelerate the reconstitution of the blood and the immune system. Furthermore, the principle of stem cell mobilization can also be applied to a wide range of indications involving tissue repair after injury. In this case, the stem cells are not collected, but migrate to the site of injury where they initiate and promote regeneration processes. In addition, in certain cancer types, e.g. leukemia, tumor cells can be mobilized by the same mechanism from their protective environment in tumor niches. Once in the circulating blood, these cells are more vulnerable to cancer chemotherapeutic drugs.
POL6326 has successfully completed first Phase I clinical trials and is currently being investigated in three different areas. In the first indication, POL6326 is applied in a combination therapy together with a marketed chemotherapeutic agent to treat patients with metastatic breast cancer. In a second trial, POL6326 is used to mobilize and collect hematopoietic stem cells from donors, which are transplanted to leukemia patients. POL6326 has shown in earlier studies first signs of efficacy, in particular a rapid and predictable onset and a dose-dependent mobilization of stem cells. The mobilization, collection of stem cells from the circulating blood (apheresis), analysis and processing of stem cells is completed in one day which represents an important competitive advantage in the hospital compared to standard therapy. The third indication concerns tissue repair in acute myocardial infarction where POL6326 may support the repair of the heart muscle after an infarction by mobilizing stem cells. An initiated Phase II study with POL6326 was not completed as it was concluded after a pre-planned interim analysis that it would be unlikely for the study to reach its primary endpoint. No safety concerns were found and the efficacy analysis suggests that certain pre-defined sub-groups of patients benefit from the treatment with POL6326. Polyphor is currently investigating the potential clinical relevance of these findings.
All clinical results generated so far show that POL6326 is generally safe and well tolerated.