Our pivotal trial, ZUMA-1, is looking at treating patients with refractory non-Hodgkin lymphoma. Non-Hodgkin lymphoma is the most common blood cancer in the US. We know that the outcome in patients with refractory disease is poor. This was recently published in a meta-analysis SCHOLAR-1 study where we looked at patients who were either non-responsive to their last line of treatment or had relapsed disease within one year after autologous stem cell transplant. In that patient population the overall response was only 26%, complete remission was less than 10% to current era available drugs. The median overall survival was only 6.5 months.

So this is the patient population that was enrolled in our ZUMA-1 study where we treated them with axicabtagene ciloleucel or axi-cel, a chimeric antigen receptor cell that’s targeting CD19. This is a multicentre phase I/II pivotal trial where 22 centres participated. The results from phase II are presented here at EHA. Patients with a diagnosis of diffuse large B-cell, primary mediastinal B-cell or transformed follicular lymphoma were enrolled and divided into two cohorts based on histology, as you see here. They were treated with two million cells per kilogram dose of axi-cel. The primary endpoint is overall response in the first 92 patients treated. By the time we dosed the 92nd patient nine additional patients were enrolled so we also show results for the total of 101 patients dosed.

ZUMA-1 has met its primary endpoint of showing statistically significant improvement in overall response compared to a historical control. The overall response rate was 82%, complete response rate was 54%. At the time of data cut-off with a median follow-up of 8.7 months the median duration of response was 8.2 months. For patients who achieved a complete response the median duration of response was not reached and is still ongoing. The median overall survival is also not reached.

Also important, as we know with CAR T-cell therapy, we can see toxicities that are not seen with chemotherapy and stem cell transplant in the form of cytokine release syndrome and neurologic events. These are relatively low at 13% for cytokine release syndrome and 28% for neurologic events. These have been generally manageable and reversible.

The main take-away point from the ZUMA-1 study is that central manufacturing and multicentre treatment are feasible for patients with CAR T. With our study we had a 99% success rate for manufacturing and 17 day turnaround between the collection of the patient’s blood cell and shipment back for axi-cel product. The response rate has been very impressive with a complete response rate at 54% which is almost seven times higher than the historical controls and median overall survival is not reached yet. In addition, the safety profile is overall safe and we also saw that for patients who received tocilizumab or steroids for the management of their symptoms or side effects did not seem to impact the clinical response. Therefore axi-cel is a very promising treatment and likely a new paradigm in the treatment for lymphoma.