Ziopharm's ZIO-101 compound may be effective against arsenic trioxide-resistant cancer

By Angela McDaniels

Seattle, Nov. 21 - Ziopharm Oncology Inc. said a study led by Lawrence Boise of the University of Miami shows that cancer cells resistant to arsenic trioxide may respond to the company's lead product candidate ZIO-101.

The study compared the cytotoxic properties and mechanism of action of ZIO-101 to arsenic trioxide in four multiple-myeloma cell lines and found that both kill myeloma cells, but different modes of action may be involved.

Data from the study can be found in a preclinical abstract published in Blood, the journal of the American Society of Hematology.

The journal also includes abstracts detailing several other studies of Ziopharm compounds ZIO-101 and ZIO-102:

• A study led by Taghi Manshouri of University of Texas showed intracellular accumulation of atomic arsenic is about eight-fold higher for ZIO-101 than for arsenic trioxide at comparable extracellular arsenic concentrations.

The compounds also appear to have different modes of action for inducing programmed cell death.

• A study led by Xiaodong Cheng of the University of Texas found the anti-leukemia activity of ZIO-101 correlates with induction of intracellular reactive oxygen species and revealed that low doses of ZIO-101 increased ROS via changes in NADPH whereas high-doses increase reactive oxygen species by disrupting electron transport in mitochondria.

These data suggest ZIO-101 may be operationally specific for cancer cells which have major defects in mitochondrial energy reserves, the company said.

• A study led by Mary Taub of the State University of New York at Buffalo found that ZIO-201, a stabilized form of isophosphoramide mustard, avoids the kidney damage caused by metabolites of ifosfamide in rabbits.

ZIO-101 is one of a family of organic arsenic compounds licensed to Ziopharm by the University of Texas M.D. Anderson Cancer Center and Texas A&M University and is currently in phase 1 clinical trials.

ZIO-201 is currently in a phase I clinical trial in advanced cancers, and the company expects to begin additional exploratory Phase 2 studies soon.

Both compounds will likely undergo a pivotal registration trial in the first half of 2007, the company said.

Ziopharm is a New York-based biopharmaceutical company that acquires and develops in-licensed cancer drugs that address unmet medical needs.

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