EVENTS | VIEW CALENDAR
Breaking through the barrier
MENLO PARK, Calif.—Seeking to enable better treatment of primary brain cancers and cancers that have metastasized to the brain, Geron Corp. has entered into a worldwide exclusive license agreement with Montreal, Canada-based Angiochem Inc. for peptide technology to facilitate the transfer of anti-cancer compounds across the blood-brain barrier (BBB).
In addition, the companies have entered into a research and collaboration agreement to put these receptor-targeting peptides to work transporting telomerase inhibitors into the central nervous system (CNS).
The license covers proprietary receptor-targeting peptides conjugated to tubulin disassembly inhibitors, including GRN1005, which was formerly known as ANG1005. GRN1005 is a novel taxane derivative that has completed two Phase I clinical trials in patients with primary brain tumors and in patients with brain metastases from breast and lung cancer.
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.
"This in-licensing augments our oncology clinical pipeline to address metastatic brain cancer, a large global unmet medical need," says Dr. Thomas B. Okarma, president and CEO of Geron. "With GRN1005, we now have an additional compound tracked to provide Phase II human proof-of-concept in 2012. The results of the completed Phase I 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 II study, we anticipate rapid marketing approval."
He adds that he and the rest of his company also look forward to collaborating with Angiochem in combining the CNS-targeting peptide technology with Geron's telomerase inhibitor technology "to enable clinical delivery of its demonstrated preclinical activity against brain cancer stem cells."
"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," adds Dr. Stephen M. Kelsey, Geron's executive vice president and chief medical officer for oncology. "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 I clinical study in brain metastases showed compelling preliminary evidence of anti-tumor activity."
The deal is important for Angiochem in part to demonstrate and facilitate its continued progress.
As Angiochem's chairman, president and CEO, Dr. Jean-Paul Castaigne, tells ddn, his company has already shown proof-of-concept for small-molecule formulations, and one of the next steps for Angiochem is to move into more work with peptides, proteins, enzymes and the like.
In addition to its concern with developing therapeutics for brain disorders and diseases that migrate to the brain, Castaigne notes that Angiochem also has a promising peptide for pain management.
"Also, for obesity we have a modified leptin able to cross the BBB," he says. "Leptin is produced by the fat cells and then is transported to the brain by the leptin transporters at the surface of the blood-brain barrier. Unfortunately in obese patients those transporters are impaired and the more you are obese, the less leptin is transported to the brain."
Also on deck is a possible treatment for Parkinson's disease, and a desire to further develop the oncology platform, with plans already forming to do more work with Geron on that front.
Castaigne says the two companies had not worked together before but found that they connected well after face-to-face meetings and found they had similar aims and outlooks.
"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," Castaigne noted in the news release about the deal. "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 two companies note. 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.
The 'why' and 'how' of GRN1005
The blood-brain barrier (BBB) prevents foreign substances, including more than 95 percent 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.
The United States alone sees approximately 200,000 cases of metastatic cancers in the brain annually and as many as half 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 upregulated 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.
Geron's clinical development plan for GRN1005 includes a Phase II clinical trial to be initiated in the second half of 2011 in patients with brain metastases arising from non-small cell lung cancer and breast cancer. Geron also plans to initiate a Phase II clinical trial in patients with glioblastoma multiforme in the first half of 2012.