ZIOPHARM Oncology, Inc. (Nasdaq: ZIOP) announced today that new preclinical data on the novel mechanism of its organic arsenic darinaparsin (ZIO-101) in various lymphoma models were presented at the 52nd Annual Meeting and Exposition of the American Society of Hematology (ASH) in Orlando Florida. Andrew M Evens, DO, MSc, Associate Professor of Medicine, Feinberg School of Medicine of Northwestern University and Director, Translational Therapeutics Division of Hematology/Oncology, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, presented the abstract (# 2840) titled "the Novel Organic Arsenical, Darinaparsin (ZIO-101), Induces Apoptosis through AKT and MEK/ERK Pathways in Hodgkin's Lymphoma and T-Cell Lymphoma Cell Lines."
“The results lend further support to the encouraging clinical data seen to date in lymphomas and warrant continued preclinical and clinical trial investigation of darinaparsin in Hodgkin's and T Cell Lymphoma.”
The preclinical work was designed to study the effects of increasing concentrations of darinaparsin in T Cell Lymphoma and resistant Hodgkin's Lymphoma. Results demonstrated that darinaparsin inhibited cell growth and induced apoptosis through the AKT and MEK/ERK pathways and all cell lines at 1-3µM. AKT and MEK/ERK-based pathways are known to play a key role in multiple cellular processes, including cell proliferation, apoptosis, transcription and cell migration. At 2µM (48 hours), darinaparsin induced approximately 80% apoptosis in each of the four TCL lines, while 3µM resulted in 65% apoptosis in L428 cells. By comparison, >10µM of arsenic trioxide or inorganic arsenic (ATO) for 48 hours was required to induce 40% apoptosis in TCL and 25% apoptosis in L428 cells. L428 cells were also treated with the MEK inhibitor U0126 or ERK2 siRNA, both combined with darinaparsin. Preincubation with U0126 or siRNA knock down of ERK2, followed by treatment with darinaparsin, significantly enhanced darinaparsin-induced apoptosis (p<0.05). Finally, markedly higher intracellular darinaparsin levels were achieved in lymphoma cells compared with equivalent concentrations of ATO.
"These data demonstrate darinaparsin's potent and targeted effects on two signaling pathways important to proliferation in hematologic malignancies, AKT and MEK/ERK, an effect which can be enhanced in combination with MEK/ERK-targeted inhibitors," said Dr. Evens. "The results lend further support to the encouraging clinical data seen to date in lymphomas and warrant continued preclinical and clinical trial investigation of darinaparsin in Hodgkin's and T Cell Lymphoma."
In September, ZIOPHARM announced that darinaparsin was granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) for the treatment of peripheral T-cell Lymphoma (PTCL). Intravenous darinaparsin has demonstrated favorable results in a Phase II trial in lymphoma and particularly for PTCL. Clinical development is expected to proceed in both PTCL and solid tumors.
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