Full Press Release Details
Expands Clinical Oncology Pipeline with License and Collaboration
Agreements with Angiochem
Worldwide License for Proprietary Peptides to Efficiently Transport
Anti-Cancer Tubulin Inhibitor Agents into CNS
to Develop GRN1005, a Phase 2 Ready CNS-Active Taxane, for Brain
Metastases and Primary Brain Cancer
to Combine Telomerase Inhibitor with CNS-Targeting Peptides
MENLO PARK, Calif. & MONTREAL--(BUSINESS WIRE)--December 6, 2010--Geron
Corporation (Nasdaq:GERN) today announced an agreement with Angiochem,
Inc. for a worldwide exclusive license to peptide technology to
facilitate the transfer of anti-cancer compounds across the blood-brain
barrier (BBB) to enable the treatment of primary brain cancers and
cancers that have metastasized to the brain. The license covers
proprietary receptor-targeting peptides conjugated to tubulin
disassembly inhibitors, including GRN1005 (formerly ANG1005), a novel
taxane derivative, that has completed two Phase 1 clinical trials in
patients with primary brain tumors and in patients with brain metastases
from breast and lung cancer. In addition, the companies entered into a
research and collaboration agreement to utilize these receptor-targeting
peptides to transport telomerase inhibitors into the central nervous
"This in-licensing augments our oncology clinical pipeline to address
metastatic brain cancer, a large global unmet medical need. In addition,
the licensed technology will enable us to develop a telomerase inhibitor
that penetrates the CNS," said Thomas B. Okarma, Ph.D., M.D. Geron's
president and chief executive officer. "With GRN1005, we now have an
additional compound tracked to provide Phase 2 human proof-of-concept in
2012. The results of the completed Phase 1 trial in brain metastases
from common cancers showed that GRN1005 is highly active as a single
agent. If these results are confirmed in our Phase 2 study, we
anticipate rapid marketing approval. We also look forward to
collaborating with Angiochem to combine the CNS-targeting peptide
technology with our telomerase inhibitor technology to enable clinical
delivery of its demonstrated preclinical activity against brain cancer
"Primary brain tumors and brain metastases present a significant unmet
medical need because drugs that might be effective against those tumors
are not able to efficiently enter the brain. GRN1005 has a demonstrated
ability to penetrate brain tissue and, more importantly, brain tumors in
nonclinical models and in patients. Furthermore, patient data from the
Phase 1 clinical study in brain metastases showed compelling preliminary
evidence of anti-tumor activity," said Stephen M. Kelsey, M.D., Geron's
executive vice president and chief medical officer, oncology.
"We are very pleased to enter into the license and the collaboration
agreements with Geron, whose clinical oncology team is highly
experienced in taking anti-cancer drugs through clinical development,"
said Jean-Paul Castaigne, M.D., Angiochem's chairman, president and
chief executive officer. "We look forward to further clinical
development of ANG1005, now GRN1005, and to collaborating on combining
our proprietary BBB-penetrating peptides with Geron's telomerase
inhibitor technology for clinical development."
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.
Angiochem will receive an upfront license fee from Geron for the
exclusive license rights. Angiochem is also entitled to receive
milestone payments, royalties on product sales and a share of
sublicensing revenues. Specific terms were not announced.
GRN1005 (Formerly ANG1005)
The blood-brain barrier (BBB) prevents foreign substances, including
over 95% of drugs, from entering the brain. This presents a practical
challenge to the treatment of brain cancer, including primary tumors as
well as brain metastases, which represent a substantial global unmet
medical need. There are approximately 200,000 cases of metastatic
cancers in the brain per year in the U.S. and up to 50% of patients die
as a direct result of intra-cerebral disease. There are currently no
drugs approved for brain metastases.
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 is comprised of three molecules of
paclitaxel, a drug with proven anti-tumor activity outside of the brain,
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. 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.
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. In addition, intra-peritoneal administration of GRN1005 in a
xenograft model of human glioblastoma resulted in a reduction in tumor
size compared to control groups treated with paclitaxel or vehicle.
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.
"It is highly encouraging to see that GRN1005 has shown the potential to
be effective in metastatic brain cancers and against drug resistant
tumors, that are highly aggressive and have few treatment options,"
commented Jan Drappatz, M.D., Center for Neuro-Oncology at Dana-Farber
Cancer Institute, Department of Neurology at Brigham and Women's
Hospital, and Harvard Medical School, and lead investigator for
Boston-area study centers. "Furthermore, significant reductions in tumor
size and reversal of neurological deficits were observed in several
cases of patients with high-grade gliomas in the Phase 1 clinical trial