GRN1005 - A Promising New Targeted Taxane Derivative

GRN1005 (formerly ANG1005) is a novel targeted taxane derivative, and represents the first oncology product to leverage the LRP-1 pathway to cross the blood-brain barrier (BBB) and enter cancer cells.

GRN1005 has solid Phase 1 clinical data demonstrating it to be highly active as a single agent, and is a Phase 2 ready CNS-active taxane for brain cancers. This small molecule product candidate has been licensed to Geron Corporation for further development.

GRN1005 Mechanism of Action

• GRN1005 gains entry into the brain by targeting the low-density lipoprotein receptor-related protein (LRP-1) which is one of the most highly expressed receptors on the surface of the BBB.

• Once inside the brain, GRN1005 enters tumor cells using the same receptor-mediated pathway through LRP-1, which is upregulated in various cancer cells including malignant glioma and metastatic cancers in the brain.

GRN1005 Clinical Data

GRN1005 has been evaluated in two separate Phase 1 multi-center, open-label, dose escalation clinical trials to identify the maximum tolerated dose (MTD) and obtain data on safety, tolerability and preliminary evidence of efficacy in patients with heavily pre-treated advanced solid tumors with brain metastases and in patients with recurrent malignant glioma.

Studying GRN1005 in Progressive Brain Metastases

Topline Results: 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 bone, liver, and lymph metastases.

Studying GRN1005 in Recurrent Glioma 

Topline Results: In the Phase 1 clinical trial in patients with recurrent glioma, 14% (4/28) of patients responded to treatment with GRN1005 with two patients achieving 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, indicating that the drug successfully crossed the BBB and was concentrated in the tumor, without showing CNS toxicity or immunogenicity.

Plasma concentrations of GRN1005, both peak concentration (Cmax) and Area Under the Curve (AUC) were several fold higher at the MTD than has been previously demonstrated with naked paclitaxel.

Toxicities related to GRN1005 were similar to other taxanes, such as paclitaxel, with dose-limiting toxicity due to neutropenia.

Data Presented at ASCO 2010

Data from the Phase 1 clinical trials of GRN1005 (formerly ANG1005) were presented at the 2010 American Society of Clinical Oncology (ASCO) annual meeting in Chicago.

> Download the posters and presentations

ASCO_2010_ANG1005_Malignant_Glioma.pdf
ASCO_2010_Solid_Tumours.pdf
Angiochem_LRP1_ASCO_2010_Castaigne.pdf
Angiochem_ANG1005_ASCO_2010_Drappatz.pdf

Further Development Plans

Geron has assembled an aggressive development plan for GRN1005 with the goal of obtaining regulatory approval in the U.S. and the rest of the world. Initial indications for further development include brain metastases from non-small cell lung cancer (NSCLC) and breast cancer. A Phase 2 clinical program has been developed to confirm the clinical activity of GRN1005 observed in earlier studies and identify relevant patient populations.