Signals Blog


Welcome to your Update from the Clinic for the month of August. Asterias Biotherapeutics breathes new life into a cell therapy shelved two years ago and initiates a Phase I/II study in patients with spinal cord injury. Northwest Biotherapeutics provides an update on the use of its dendritic cell-based immunotherapy in patients with brain cancer. Read on to find out more.

Many of us will remember the hype and excitement surrounding Geron’s (GERN) launch of the world’s first clinical study of an embryonic stem cell-derived cell therapy back in 2009, and the disappointment that resonated within the biotechnology community when the company made the seemingly hasty decision, just two years later, to shelve the therapy indefinitely. Some understood it to be a shrewd business decision to streamline the company’s focus, while others were left wondering why the company had entered the space in the first place.

The technology under investigation (then known as GRNOPC1) was a line of oligodendrocyte progenitors derived from human embryonic stem cells. It was divested from the company two years after it was shelved, in October 2013, to California-based BioTime (BTX), after a long period of negotiations. BioTime received a total of four cell banks in the deal, including GRNOPC1, a cancer vaccine at the Phase II stage, and two other cell lines being investigated to treat heart failure and osteoarthritis.

Asterias Biotherapeutics, a subsidiary of BioTime and beneficiary of the late Geron cell lines, has just received FDA clearance for a Phase I/II study investigating AST-OPC1 in patients with complete cervical spinal cord injury. The new clinical development program follows the successful completion of a Phase I study by Geron, where five patients were treated and had no adverse events. The Phase I/II study will continue to investigate safety while ramping up dosing of the progenitor cells to analyze activity following transplantation. Asterias is partnering with the California Institute for Regenerative Medicine (CIRM), which has agreed to provide $14.3 million in non-dilutive funds to kick-start the program.

Northwest Biotherapeutics (NWBO), which recently completed a $17.5 million debt financing to continue pushing forward with clinical validation of its DCVax® technology for the treatment of Glioblastoma multiforme (GBM), provided an update on its Phase III clinical study. The company reported that, in conjunction with completion of the study in 2011 and 2012, it created an “Information Arm” outside of the Phase III study for 55 compassionate use patients who did not originally qualify for enrolment.

Patients in the compassionate use group were so called “rapid progressors,” exhibiting new tumour growth within the 6-week session of daily radiation and chemotherapy treatments. Generally these patients are excluded from clinical studies in GBM due to their extremely poor prognosis and the speed of disease progression they display. Rapid progressors survive, on average, seven to 10 months following diagnosis, whereas regular GBM patients survive 14.6 months with the current standard of care. Despite this, median overall survival for the 55 compassionate use patients was 18 months following treatment with DCVax® – a very significant increase.

Interestingly, the company has also been granted permission to make amendments to the statistical analysis carried out following the Phase III study. Regulatory authorities in the U.S., UK and Germany all gave approval for the changes on the basis that a “major new variable” has been identified in GBM research since launch of the study, which affects patients’ survival times.

Concerned that study results will be skewed as a result of the new finding, NWBO is implementing additional statistical measures to ensure it is controlled for adequately. The variable involves the level of white blood cells found in the brain following six weeks of radiation therapy, which apparently can be as low as those observed in AIDS patients. The impact of this condition on survival time in GBM patients is immense. Patients with severely depressed white blood cell counts in the brain can experience a reduction in survival time of up to six months. To put this into perspective, the current standard of care for GBM, Temodar, only makes a difference of 10 weeks to patients’ overall survival (OS). So, the identification of this patient subset will have important implications for the stratification of GBM patients in the clinic.

As a result of the changes to the statistical analysis arising from the new findings, NWBO will be able to reduce the threshold seen in progression-free survival (PFS) between the treatment and control arms from six months to four months on the basis that patient numbers will increase from 312 to 348 and the number of events counted (tumour recurrence or death) to assess the primary endpoint will increase from 110 to 248.

Glioblastoma multiforme is a very challenging cancer to treat given its location in the body. Targeted therapies are especially critical here for improving PFS and OS. Similar to treatment protocols for many cancer indications, the current standard of care in GBM is to debulk tumours with surgery prior to administering therapeutic agents. Cell therapies that elicit immune responses targeted to GBM to clean up residual cancer cells following debulking (a process to diminish tumour mass) should have a place in future treatment strategies. For an example of an early-stage, but cutting-edge, technology check out this article discussing the use of virus-loaded mesenchymal stem cells embedded in biocompartible hydrogels for treating GBM.


Disclaimer: “Update from the Clinic” is a blog post generated by news flow from public regenerative medicine (RM) companies around the globe. As CCRM has public RM companies in its industry consortium, and the number of such companies is relatively limited on a global scale, Mark Curtis will sometimes include CCRM consortium members in his review. This blog post is provided for general information only and nothing contained in the material constitutes a recommendation for the purchase or sale of any security. The author is not a shareholder of any public RM company. To see a list of CCRM’s industry consortium members, please visit





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Mark Curtis

Mark Curtis

Mark is a Business Development Analyst at the Centre for Commercialization of Regenerative Medicine (CCRM), where he collaborates with the team to help evaluate the commercial potential of regenerative medicine and cell therapy technologies. He began his career at Princess Margaret Hospital studying cellular reprogramming of human skin cells. Following this project, he left the laboratory and took on a role with Bloom Burton & Co., a healthcare-focused investment dealer. While there he supported the advisory team in carrying out scientific diligence on early-stage biotechnology companies. Prior to joining CCRM he was a consultant to Stem Cell Therapeutics, a Toronto-based biotechnology company focused on developing therapeutics targeting cancer stem cells. Mark received a Master’s degree from the University of New South Wales in Sydney, where he studied the directed differentiation of embryonic stem cells, and a Bachelor’s degree in Biology, from Queen’s University. Follow Mark on Twitter @markallencurtis
Mark Curtis

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