ZIOPHARM reports promising preclinical data with palifosfamide in pediatric sarcoma model

ZIOPHARM Oncology, Inc. (Nasdaq: ZIOP), a drug development company employing small molecule and synthetic biology approaches to cancer therapy, today announced the presentation of promising preclinical data with palifosfamide (Zymafos™ or ZIO-201) in a pediatric sarcoma model. The data was detailed in an oral session of the 2011 meeting of the combined Connective Tissue Oncology Society (CTOS) Musculoskeletal Tumor Society (MSTS), being held October 26 - 29, 2011 in Chicago, IL.

The presentation, entitled "Palifosfamide, a Bifunctional DNA Alkylator, Inhibits Growth of Pediatric Sarcoma Xenografts Across a Wide Dose Range Following Oral and Parenteral Dosing," addressed, among other findings, the impact of palifosfamide activity in the presence of overexpression of aldehyde dehydrogenase (ALDH), an enzyme thought to confer resistance to alkylators like cyclophosphamide and ifosfamide. The authors reported that palifosfamide, a bi-functional DNA-alkylator in class with ifosfamide, cyclophosphamide and bendamustine, did not exhibit ALDH resistance. This important finding, combined with the use of oral administration and a potentially favorable toxicity profile, are particularly relevant for the pediatric population.

In vivo modeling for the study was conducted in the Cancer Therapeutics Laboratory of the Alfred I. DuPont Hospital for Children. The authors included E. Anders Kolb, M.D., Director, Blood and Bone Marrow Transplantation and Head, Cancer Therapeutics Laboratory as lead author and Richard Gorlick, M.D., Vice Chairman of Pediatrics at Albert Einstein College and Chairman of the Children's Oncology Group (COG) Bone Sarcoma Committee as senior author. Results showed that orally administered palifosfamide was found to have broad in vivo preclinical activity comparable to parenteral administration in an osteosarcoma model. This activity was measured by tumor growth delay, relative tumor volume (RTV) and event-free survival across all doses. Investigators also found palifosfamide active in xenografts with overexpressed levels of ALDH. Overexpression of ALDH is present in diverse tumor types including breast cancer, colon cancer, pancreas cancer, Ewing's sarcoma and other cancers, and is a marker of cancer stem cells. Ongoing testing of dose and schedule in both sarcoma and breast cancer models will define future clinical evaluation of the oral form and was supported through mathematical applied Norton-Simon modeling, as established by Larry Norton, M.D., deputy physician-in-chief for breast cancer programs, at Memorial Sloan-Kettering Cancer Center and an author of the study.

"The overexpression of ALDH in cancer cells may confer cancer stem cell-like activity and resistance to treatment, including chemotherapy and, in particular, ifosfamide and cyclophosphamide," stated Dr. Kolb. "As a stabilized form of the active metabolite of ifosfamide, palifosfamide bypasses resistance mediated by ALDHs, in addition to conferring a potentially favorable toxicity profile compared to ifosfamide, which is known to generate toxic metabolites such as acrolein and chloroacetaldehyde. These results are compelling and merit further exploration in the clinic."

The study was funded through a grant awarded to Dr. Lewis and Dr. Gorlick by the Kristen Ann Carr Fund (KACF) for the development of a novel treatment for pediatric sarcoma. The study's objectives were to set the stage for further clinical study in pediatric sarcoma and other childhood cancers. Formed in 1993 in honor of Kristen Ann Carr (1971-1993), the KACF provides funding for the research and treatment sarcoma as well as the education of young physicians through the Kristen Ann Carr Fellowship at the Memorial Sloan-Kettering Cancer Center. Dr. Lewis was the first Kristen Ann Carr Fund Fellow (1993-1995), an honor awarded to him while at Memorial Sloan-Kettering.

Dr. Gorlick commented: "Sarcoma is a disease of high mortality which affects proportionately far more children than adults. It is, therefore, a critical goal of pediatric oncology research to find safer, more effective treatment options for this population. An oral drug could be a breakthrough in pediatric oncology treatment. These early, yet promising, results show the potential of palifosfamide to address this unmet medical need."