Angiochem, Inc., a clinical-stage biotechnology company developing drugs that are uniquely capable of crossing the blood-brain barrier (BBB) through LRP-1 targeting, announced today that preclinical data was presented on two of its oncology programs, ANG1005 and ANG1007, for the treatment of brain cancers at the 101st Annual meeting of the American Association for Cancer Research 2010, April 17-21, in Washington, DC. These data demonstrated that Angiochem's novel anticancer agents target the low density lipoprotein receptor-related protein (LRP-1) pathway to achieve efficient penetration rates in the brain and tumor cells.
“Angiochem's LRP-1 targeting has the potential to transform chemotherapeutic agents, such as paclitaxel and doxorubicin, to a new level of effectiveness for the treatment of gliomas by enabling penetration of the drug through the BBB and multi-drug resistance mechanisms”
Angiochem researchers presented preclinical data validating the effectiveness of LRP targeting by ANG1005, Angiochem's most advanced product candidate which has successfully completed Phase 1/2 clinical trials in glioblastoma (GBM) and brain metastases. These preclinical data demonstrated effective transport of ANG1005 into glioblastoma cells as well as in the transcytosis of ANG1005 at the blood BBB through the LRP-1. The study demonstrated an increased uptake of ANG1005 in implanted GBM brain tumors using in vivo imaging as compared to normal brain tissue, indicating that LRP-1 is over-expressed in GBM cells and the GBM tumor microenvironment favors ANG1005 uptake. This study provides further evidence that ANG1005 can be an effective therapy to treat aggressive brain cancers such as GBM.
In addition, preclinical data was presented demonstrating that ANG1007, a new anticancer compound from Angiochem's Engineered Peptide Compounds (EPiC) platform, achieved greater penetration of doxorubicin to the brain and cancer cells than native doxorubicin and circumvented multi-drug resistant cancer mechanisms. In mouse brain perfusion studies, ANG1007 was transported efficiently across the BBB at a rate 10-fold higher than native doxorubicin and inhibited cancer cell proliferation in vitro, with highly cytotoxic activities against various tumor cell lines. In addition, brain perfusion studies performed with P-gp knockout mice showed that ANG1007 bypassed multi-drug resistant mechanisms, inhibited the growth of glioblastoma tumors and increased survival of mice implanted with brain tumors.
"Angiochem's LRP-1 targeting has the potential to transform chemotherapeutic agents, such as paclitaxel and doxorubicin, to a new level of effectiveness for the treatment of gliomas by enabling penetration of the drug through the BBB and multi-drug resistance mechanisms," said Jean-Paul Castaigne, MD, President and CEO of Angiochem. "In total these data confirm that targeting the LRP-1 receptor validates Angiochem's product-generating platform for the development of novel brain cancer therapies."
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