How are the Geron patients doing?
Asterias: They are doing well. We have to remember that they got the lower dose (2 million OPC1 cells) and we estimated that the efficacy dose was more like 10-20 million cells. The good thing is that the safety profile is very strong. The trial offers 15 years follow up including 5 years of MRIs and after that phone follow up. There is so far sustained evidence of prevention associated with cavity formation in 4 out of 5 patients, which implies durable engraftment. Out to 1 year no evidence of an antibody or T cell response to OPC1 cells. We will see that out to 5 years. No masses or tumors or even health issues attributable to cells. We are very excited by all those safety data, which were also submitted to the FDA.
Are AST-OPC1 heterogeneous?
Asterias: The overwhelming percentage of cellular material are OPCs. In the spirit of full disclosure there are several other characterized cell types in the mix too. We have been working to more fully characterize those cells. In the old days lots of characterization was done by immunostaining. Now we are performing RNA-Seq and other more up to date studies. An interesting question can be: do any of the other minor players (cell types) contribute?
What happens with the AST-OPC1 prior to Day zero? Is it a thaw-and-go kind of situation or do the tissues get cultured for a while?
Asterias: The cells are thawed and washed (to remove cryopreservative) on the day of surgery. This takes 2-3 hours and is typically done in the morning. STAT g stain is also done and once they pass, they are after that released to the OR for injection. Another sample can be sent for 14-day sterility test. So there is no development of the cells prior to injection, just washing and resuspension into the injection medium. We find there’ s about 80 percent viability.
Can you update us on the spinal cord injuries trial? How do we tell the difference between a restorative effect and spontaneous recovery?
Asterias: So this is something that has been researched in detail by the SCOPE (spinal cord outcomes partnership endeavor) group with Dr . John Steeves Professor at UBC and Andy Blight, the Acorda therapeutics CSO. There were some papers published. What is the SCI rate of recuperation with standard of care? The majority of patients with an United states Spinal Injury Associate (ASIA) Impairment Scale Grade The injury (known as an AIS A injury) will recuperate 1 motor level on one side of the body. Few of these patients spontaneously recovery 2 motor levels, actually over the longer term. With OPC1, our goal is 40-50% of patients having > = 2 motor ranges on one side of body, which is well beyond regular spontaneous recovery, and so far by day 90 several of our patients in the 10 million cell cohort got already recovered 2 motor levels (that was the 6 month target). We haven’ t tested the particular 20 million dose yet, but believe there’ h potential for further improvements with this higher dose. The dosage response related to motor score is encouraging so far with regards to the 2 million and 10 million cell doses.
Can you tell me more about the complete thoracic compared to subacute cervical trials? What are the differences in the patients for example?
Both studies tested patients along with severe impairment. The thoracic study and the first 3 cohorts of the cervical study were in patients along with AIS A injuries, which is complete loss of motor plus sensory function below the site of injury. We furthermore recently got permission to expand the study to 2 additional cohorts of patients with AIS B accidental injuries. These patients have complete loss of all motor functionality but some preserved sensory function below the level of their injuries.
Both studies are similar.
A single difference between the original thoracic and the current cervical research is timing of delivery of OPC1. In the first study in thoracic injuries, Geron injected OPC1 inside 7-14 days of injury; in the ongoing Asterias cervical research, there is a 14-30 days post-injury window. 14 days is extremely limited, while 14-30 is more feasible. Most of the patients got it near to the 30-day cutoff. The reason scientifically we are focusing on the subacute window is that there is a sense we will obtain better engraftment in that period. We want to avoid the early inflammation and the scarring formation period (begins ~3 months). We could push the particular window out a few more weeks. The rationale for also entering cervical is that if you can mediate anatomical repair, via OPC stimulating endogenous repair, collectively over several segments, in the event that can mediate functional repair, it can have a huge impact on the person’ s quality of life.
Any expect lower extremity function restoration?
Asterias: It’ s a tall purchase for the severe injury cases such as patients with AIS A injuries. In these patients we believe improvements within upper extremity function are far more feasible. In much less severe, AIS C injuries (in which some degree of both sensory and motor function are preserved beneath the level of the injury), there may be a good chance for some lower-leg motor function recovery.
Any unwanted effects including of immunosuppression?
Asterias: There have been no clear negative effects of immunosuppression. Going into the study the primary concern regarding immunosuppression was can infections be more frequent or worse? We tried to restrict the immunosuppression to low dose and short term to be able to minimize this risk. So far in the study we haven’ t seen any evidence of increased infections, which is stimulating.
What about company policy regarding demo participants and the media? We’ ve seen at least one affected person talking to the media.
Asterias: Several of our patients have chosen to create public statements regarding their participation in our study. This really is their choice to make. So much has been taken away from their lifestyles. They’ ve seen benefit so understandably they such as the idea of expressing what they’ ve experienced and they wish to educate other patients. Their doctors communicated to all of us that the patient is interested in talking. There are HIPPAA factors.
What are your future plans and do they will include RCTs?
Asterias: The logical next phase is a randomized managed trial. We’ re currently enrolling in our single supply, open label trial for the AIS A 20 mil cell dose cohort and the AIS B 10 mil cell cohort (and later 20 million). That is anticipated to wrap up Q3-4 next year. As the data come in, we can create plans.
The next big readout is The month of january of 2017 when we should have cumulative 6-month data for that AIS A patients at 10 million cells. five patients.
As this and other data from the following cohorts become available, we’ ll examine data, talk with researchers, the FDA, etc . to determine our plans for following trials.
Do you have any non-SCI-related operate the pipeline?
Asterias: OPC1 could be helpful for other indications. We have carried out some preclinical work related to MS and certain types of stroke, which have been encouraging. Some pediatric conditions. Overall, we would like to get that first clinical win before we go after other areas.
Disclosure: I have no monetary ties to Asterias.