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Dec 7, 2010

Angiochem and Geron Ally to Tackle Brain Cancer and Metastases

Angiochem and Geron Ally to Tackle Brain Cancer and Metastases

Geron gains access to peptide technology that facilitates movement across the BBB and a Phase II compound.[V. Yakobchuk/Fotolia.com]

  • Geron obtained a worldwide, exclusive license to Angiochem’s peptide technology, which is expected to help anticancer agents move across the blood-brain barrier (BBB). The aim is to enable the treatment of primary brain cancers and cancers that have metastasized to the brain.

    Angiochem will receive an up-front license fee and is entitled to milestones, royalties, and a share of sublicensing revenues. The deal covers receptor-targeting peptides conjugated to tubulin disassembly inhibitors, including Phase II ready candidate GRN1005 (formerly ANG1005). The firms also entered a research and collaboration agreement to utilize these receptor-targeting peptides to transport telomerase inhibitors into the central nervous system (CNS) and target brain cancer stem cells.

    Geron has one clinical telomerase inhibitor candidate, GRN163L, in six early-stage trials as a treatment against a variety of cancers including breast cancer, multiple myeloma, and non-small-cell lung cancer (NSCLC). It also has a telomerase cancer vaccine, GRNVAC1, in a Phase II acute myelogenous leukemia study.

    GRN1005 completed two Phase I trials in patients with primary brain tumors and in patients with brain metastases from breast and lung cancer. Geron plans on initiating a Phase II trial in the second half of 2011 in patients with brain metastases arising from breast cancer and NSCLC. The company also expects to start a Phase II study in patients with glioblastoma multiforme in the first half of 2012.

    The drug is designed to exploit a natural mechanism by which essential substances such as lipids and hormones successfully enter the brain through receptors in the BBB. GRN1005, a taxane derivative, comprises three molecules of paclitaxel linked to a proprietary peptide that targets the lipoprotein receptor-related protein-1 (LRP-1), one of the most highly expressed receptors on the surface of the BBB, the companies say. Binding to LRP-1 facilitates receptor mediated transcytosis across the BBB into the brain tissue.

    LRP-1 is also up-regulated in many tumors including malignant glioma and metastatic cancers both in the brain and visceral organs. Hence the GRN1005 has the ability to enter tumor cells in the brain as well as in the periphery using the same receptor-mediated pathway.

    Telomerase is a critical and broadly applicable tumor target. The enzyme is expressed in a wide range of malignant tumors, and its activity is essential for the indefinite replicative capacity of cancer that enables malignant cell growth. Telomerase has now also been shown to be a target for cancer stem cells.

    Preclinical animal studies have shown that administration of GRN1005 led to high concentrations of paclitaxel in the brain, compared to concentrations achieved by administration of naked unconjugated paclitaxel. The compound also demonstrated preliminary evidence of single agent activity against brain metastases arising from a variety of epithelial malignancies including breast cancer, NSCLC, and ovarian cancer.

    In the Phase I trial the response rate of patients who received therapeutic doses of GRN1005 was 24% (5/21). At the maximum tolerated dose, the response rate was 42%. Furthermore, 33% of patients previously treated with a taxane responded to treatment with the drug, indicating that it has the potential to be effective against paclitaxel-resistant tumors. In addition to metastases in the brain, responses were also observed in liver and lung metastases in patients who had previously progressed on paclitaxel.

    In the Phase I trial in patients with recurrent glioblastoma, 14% responded to the therapy, and two patients achieved a complete response. Therapeutic doses of GRN1005 were present in brain tumor samples taken from patients who had received a single dose of the drug.


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