MedKoo product information:

GRN-1005

GRN1005 is comprised of three molecules of paclitaxel, a drug with proven anti-tumor activity outside of the brain, linked to a proprietary peptide (19-amino-acid peptide Angiopep-2) that targets the lipoprotein receptor-related protein-1 (LRP-1), one of the most highly expressed receptors on the surface of the BBB. Binding to LRP-1 facilitates receptor mediated transcytosis across the BBB into the brain tissue. Importantly, LRP-1 is also up-regulated in many tumors, including malignant glioma and metastatic cancers both in the brain and visceral organs, enabling efficient entry to tumor cells in the brain and in the periphery using the same receptor-mediated pathway. A critical characteristic of GRN1005 is its anti-tumor activity in both the intra-cerebral and extra-cerebral compartments.

ANG1005 (now GRN1005), a novel taxane derivative, for which Angiochem has performed two Phase 1 clinical trials in patients with primary brain tumors and in patients with brain metastases from breast and lung cancer. GRN1005 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 demonstrated preliminary evidence of single agent activity against brain metastases arising from a variety of epithelial malignancies, including non-small cell lung cancer (NSCLC), breast cancer and ovarian cancer. In the Phase 1 clinical trial, the response rate of patients who received therapeutic doses of GRN1005 was 24% (5/21). At the MTD, the response rate was 42% (5/12). Furthermore, 33% (4/12) of patients previously treated with a taxane responded to treatment with GRN1005, indicating that GRN1005 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. The nature of the toxicities related to GRN1005 was similar to other taxanes, such as paclitaxel, with dose-limiting toxicity due to neutropenia. At the recommended Phase 2 dose of 650mg/m2 the frequency of severe neutropenia was greater than for naked paclitaxel but this was easily manageable and did not compromise dosing. (source: http://www.geron.com/products/productinformation/GRN1005.aspx).

Current developer:    Geron. / Angiochem.

1: Bertrand Y, Currie JC, Poirier J, Demeule M, Abulrob A, Fatehi D, Stanimirovic D, Sartelet H, Castaigne JP, Béliveau R. Influence of glioma tumour microenvironment on the transport of ANG1005 via low-density lipoprotein receptor-related protein 1. Br J Cancer. 2011 Oct 25. doi: 10.1038/bjc.2011.427. [Epub ahead of print] PubMed PMID: 22027709.

2: Wen PY. American Society of Clinical Oncology 2010: report of selected studies from the CNS tumors section. Expert Rev Anticancer Ther. 2010 Sep;10(9):1367-9. PubMed PMID: 20836670.

3: Thomas FC, Taskar K, Rudraraju V, Goda S, Thorsheim HR, Gaasch JA, Mittapalli RK, Palmieri D, Steeg PS, Lockman PR, Smith QR. Uptake of ANG1005, a novel paclitaxel derivative, through the blood-brain barrier into brain and experimental brain metastases of breast cancer. Pharm Res. 2009 Nov;26(11):2486-94. Epub 2009 Sep 23. PubMed PMID: 19774344; PubMed Central PMCID: PMC2896053.

4: Régina A, Demeule M, Ché C, Lavallée I, Poirier J, Gabathuler R, Béliveau R, Castaigne JP. Antitumour activity of ANG1005, a conjugate between paclitaxel and the new brain delivery vector Angiopep-2. Br J Pharmacol. 2008 Sep;155(2):185-97. Epub 2008 Jun 23. PubMed PMID: 18574456; PubMed Central PMCID: PMC2538693.