Welcome to your Update from the Clinic for the month of August. The adult stem cell community enjoyed a much needed confidence boost after TiGenix announced its Phase 3 trial hit its primary endpoint. Northwest confirmed its Phase 3 trial of DCVax in glioblastoma is still underway despite rumours that the trial had been halted due to safety concerns. OncoSec announced its first patient has been treated in a study investigating IL-12 in combination with a checkpoint inhibitor from Merck.
The last two years have been challenging for the adult stem cell field, having endured two consecutive failures from Athersys in ulcerative colitis and ischemic stroke. However, TiGenix (TIG), based in Belgium, has reinvigorated the field after hitting the primary endpoint in its Phase 3 study investigating adipose-derived allogeneic stem cells (Cx601) for the treatment of complex perianal fistulas in patients with Crohn’s disease. Adult stem cells have historically had issues with quality control and characterization, especially so-called “MSCs,” which can be derived from many sources, including the bone marrow, umbilical cord, and adipose tissue. The primary endpoint in the TiGenix study was combined remission (closure of all external openings) at 24 weeks. In the intention-to-treat population Cx601 achieved statistically significant superiority with 49.5 percent of patients satisfying the primary endpoint compared to only 34.3 percent in the placebo group.
Northwest Biotherapeutics (NWBO) saw 25 percent of its market capitalization disappear overnight after rumours spread that the company had halted its Phase 3 clinical study investigating DCVax in patients with glioblastoma multiforme. NWBO was quick to issue a press release that, while patient enrollment has been temporarily suspended, patients currently enrolled in the study continue to be treated per the study protocol. Rumours started to spread after it was reported on social media sites that the EudraCT database in Europe updated the trial’s status in Germany to “Temporary Halt.” While this is not entirely true, the database was not designed to allow for status changes indicating a temporary suspension in patient enrollment. In order to get enrollment back up and running, NWBO must submit certain documents for regulatory review. The trial has currently enrolled 300 of 348 patients.
Merck and OncoSec Medical (ONCS) are combining powers to investigate the synergistic activity of IL-12 immunotherapy and a PD-L1 checkpoint inhibitor. OncoSec’s ImmunoPulseTM IL-12 technology includes a DNA plasmid encoding IL-12 and a handheld electroporation device that is used to deliver the plasmid to cancer cells in situ. Following up-take of the plasmid, cancer cells begin to secrete IL-12, which modulates the tumour microenvironment in such a way that drives a local inflammatory response, alerting the host’s immune system to the cancer’s presence.
Investigators at the University of California San Francisco (UCSF) will lead the study and will study the therapeutics together in patients with unresectable (i.e. unable to be removed with surgery) metastatic melanoma. The patient subset targeted will be those individuals who exhibit low levels of tumour infiltrating lymphoctyes (TILs) in their lesions (white blood cells that enter tumours to kill cancer cells). It is believed that OncoSec’s IL-12 immunotherapy, which acts to increase tumour immunogenicity, along with checkpoint inhibition by way of Merck’s Keytruda® (pembrolizumab), will deliver synergistic therapeutic activity. Typically checkpoint inhibitors require the presence of white blood cells in a tumour to be highly effective. We will be seeing lots of this type of collaborative activity in years to come, as immunotherapy companies strive to maximize clinical impact through combinatorial regimes.
OncoMed (OMED) completed enrollment for its Phase 2 ALPINE clinical study investigating tarextumab in patients with pancreatic cancer. OMED’s antibody programs target cancer stem cells. Tarextumab is designed to inhibit notch signaling by targeting the Notch2 and Notch3 pathways. In addition to the ALPINE study, tarextumab is being investigated in the PINNACLE study. ALPINE is investigating tarextumab in combination with Abraxane and gemcitabine in first-line advanced pancreatic cancer, while PINNACLE will study the therapy in combination with etoposide and cisplatin or etoposide and carboplatin in first-line extensive stage small cell lung cancer.
Historically, there has been a good deal of debate as to whether the cancer stem cell theory, which is the accepted model of cancer formation for liquid cancers of the bone marrow, applies to solid tumours. More recently, new data have begun to support the notion that a “tumour initiating cell” does exist in multiple solid tumours. OncoMed, Stemline Therapeutics and VeraStem are placing early bets in the field of cancer stem cells, as are Canada’s Trillium Therapeutics and Actium Research. An up-and-comer in the field of cancer stem cell therapeutics is privately held Stemcentrx. Similar to the work of Dr. John Dick, who first postulated the cancer stem cell theory and subsequently proved that leukemic stem cells exist, Stemcentrx is studying the activity of subsets of tumour cells following transplantation into rodents. By pairing this with flow cytometry, the company is hoping to identify and characterize tumour-initiating cells from a variety of solid tumours. Investors clearly like the idea; according to the Wall Street Journal the company’s valuation is currently US$5 billion. How this is justified at the preclinical stage is a bit of a mystery, but we will be watching closely!
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 http://ccrm.ca/industry-consortium.