First Patient Randomized for ACTIsSIMA Trial for Chronic Stroke

SanBio, a regenerative medicine company in Mountain View, California, has announced the randomization of the first enrolled patient in the ACTIsSIMA Phase 2B clinical trial. This trial will examine the efficacy of SanBio’s proprietary SB623 product in patients who suffer from chronic motor deficits as a result of strokes. SB623 consists of modified adult bone-marrow-derived stem cells. A secondary purpose of this trial is to evaluate the safety of SB623 in these patients.

Ischemic strokes account for about 87 percent of all strokes in the United States. Ischemic strokes occur when there is an obstruction in one or more of the blood vessels that provide blood and oxygen to the brain. On the order of 800,000 cases of ischemic stroke occur in the United States every year, and it is the leading cause of acquired disability in the United States. Present drug treatments for stroke either try to prevent strokes or address patients who have recently suffered a stroke. Unfortunately, there are no medical treatments currently available for people who live with the effects of stroke, months or even years after suffering a stroke.

SB623 cells are derived from bone marrow mesenchymal stem cells extracted from healthy donors. These cells are designed to promote recovery from injury by triggering the brain’s natural regenerative ability. SB623 cells have been genetically engineered to express a modified version of the Notch gene (NICD) that conveys upon the cells the ability to promote the formation of new blood vessels and the survival of endothelial cells that form these new blood vessels (see J Transl Med. 2013, 11:81. doi: 10.1186/1479-5876-11-81).

SB623 was tested in a Phase 1/2A clinical trial in which SB623 was implanted into stroke patients and produced some improved motor function.

This follow-up trial, ACTIsSIMA, will treat stroke patients with SB623 cells in order to examine the safety and efficacy of SB623 cells. All patients in this trial have suffered from a stroke anywhere from six months to five years. Also, all patients must exhibit chronic motor impairments.

Damien Bates, M.D., Chief Medical Officer & Head of Research at SanBio, said, “Our previous trial suggested there was potential for SB623 to improve outcomes for patients with lasting motor deficits following an ischemic stroke. Randomization of the first subject marks an exciting step toward further evaluating this treatment as a promising new option for patients.”

For this trial, SanBio is collaborating with Sunovion Pharmaceuticals, Inc. Sunovion is a wholly owned subsidiary of Sumitomo Dainippon Pharma Co., Ltd., and SanBio and Sumitomo Dainippon Pharma have entered into a joint development and license agreement for exclusive marketing rights in North America for SB623 for chronic stroke.

The ACTIsSIMA trial will include approximately 60 clinical trial sites throughout the United States, and total enrollment is expected to reach 156 patients.

SanBio Tests Its Mesenchymal Stem Cell Line SB623 as a Treatment for Strokes

California-based biotechnology company, SanBio Inc., has announced the successful enrollment of its first patients in a Phase 1/2a clinical trial that will test the safety and efficacy of a novel stem cells product in the treatment of chronic deficits that are the product of strokes. This stem cell product is called SB623, and so far, 6 of 18 patients have been given this product. This clinical trial is being conducted at the University of Pittsburgh and Stanford University. The trial is being conducted at Stanford University and the University of Pittsburgh. Thus far, no safety concerns have been reported.

SB623 is a stem cell line that was originally derived from adult bone marrow stem cells. Specifically, mesenchymal stem cells were isolated from bone marrow and cultured. They were then genetically engineered to express a modified version of the “Notch” gene. The Notch gene encodes a protein that is embedded into the membrane and has regions that extend to the cell exterior and another portion that extends to the cell interior. The scientists who made SB623 forced the mesenchymal stem cells to express the internal portion of the Notch protein. The significance of this is simple; the internal portion of the Notch protein does all the work and the external portion of it regulates the internal portion. By expressing only the internal portion of the Notch protein, the scientists made a version of the Notch protein that is always active. When active, the Notch protein turns mesenchymal stem cells into cells that support neurons, which are the main functional cells of the nervous system that transmit neural impulses.  Therefore, SB623 cells are derivatives of mesenchymal stem cells that have the capacity to form neurons or cells that greatly resemble neurons.

SanBio scientists and others have used SB623 cells in laboratory rodents that have sufered strokes. In all animal studies, SB623 cells appear to be safe and efficacious. Tate and colleagues published a paper in the journal Cell Transplantation in 2010 entitled, “Human mesenchymal stromal cells and their derivative, SB623 cells, rescue neural cells via trophic support following in vitro ischemia.” This paper (Cell Transplant. 2010;19(8):973-84), SB623 cells were co-cultured with brain slices after those slices had been deprived of oxygen, which is exactly what happens to the brain during a stroke. SB623 cells or the medium that was used to grow SB623 cells rescued cells in the brain slices from dying. This effect was also dosage dependent.

In an earlier paper, SanBio scientists showed that SB623 cells made scaffolds of molecules that supported the growth of neurons (Aizman et al., J Neurosci Res. 2009 Nov 1;87(14):3198-206). In other work, scientists at Northwestern University implanted SB623 cells into the brains of rats with Parkinson’s disease and showed that they prevented the death of dopaminergic neurons; the cells that usually die during Parkinson’s disease (Glavaski-Joksimovic A,, et al., Cell Transplant. 2009;18(7):801-14). Therefore, the use of SB623 cells in rodents points to a potential for these cells as therapeutic agents in human disease.

The Chief Executive Officer for SanBio, Keita Mori, said of this trial, “This represents a major milestone in the human clinical testing of this important new approach for regenerative medicine. We are pleased to learn that the initial dose level was well tolerated.” In this clinical trial, SB623 is implanted into the damaged region of the brains of stroke patients. Product safety is the primary focus of the study; however, particular tests and measurements of efficacy are also being tested.

SanBio’s Vice President of Development, Ernest Yankee said, “The successful completion of the initial dose cohort is a major step in any first-in-human study. We are looking forward to initiating the next two dose cohorts and wrapping up the study. The safety findings thus far are very encouraging”