ZIOPHARM PRESENTS DATA ON TREATMENT FOR PEDIATRIC SARCOMA

Ziopharm Oncology has presented new data on the effect of ZIO-201 on several human pediatric sarcoma models (Ewing sarcoma, rhabdomyosarcoma, synovial sarcoma and osteosarcoma) demonstrating potent anti-cancer activity. The results were comparable for ZIO-201 administered as a single dose, a schedule currently being explored in Phase I clinical studies, or as three consecutive daily doses, as is scheduled in the initial Phase I and the sarcoma Phase I/II trials. Also, ZIO-201 was active in cyclophosphamide-resistant osteosarcoma, the most common pediatric bone cancer in the U.S., according to the company.

Resistance to cyclophosphamide (CPA) and ifosfamide (IFOS) is a major obstacle to overcome in cancer treatment, according to Ziopharm. CPA and IFOS are prodrugs that cannot kill cells unless activated by the intracellular enzyme aldehyde dehydrogenase 3A1 (ALDH). Cancer cells typically escape killing by CPA and IFOS by developing high intracellular levels of ALDH. Because ZIO-201 (isophosphoramide mustard) is the activated form of IFOS, killing of sarcoma cells is direct and immediate and does not require activation by ALDH. Similarly, high intracellular levels of ALDH should not inhibit sarcoma cell killing by ZIO-201, the company said.

ZIO-201, the active moiety of IFOS, is a bifunctional alkylator that causes irreparable inter-strand DNA cross-linking resulting in cell death. ZIO-201 is as or more active than IFOS in diverse cancer models. Unlike IFOS, ZIO-201 is not metabolized to acrolein or chloracetaldehyde, which can cause bladder or central nervous system toxicities. ZIO-201 is in Phase I and I/II trials in diverse cancers exploring maximum tolerated dose at alternate schedules.