Year 1

By accelerating translation of stem cell related discoveries to the clinic, the CIRM Alpha Stem Cell Clinic at UC San Diego has made several advances in the fields of diabetes, spinal cord injury, leukemia and heart failure. The majority of our trials represent Phase 1 trials and as with all Phase 1 trials, the main goal is to establish safety and tolerability of the approach.

First, a first-in-human trial to evaluate the safety and tolerability of a device (EncaptraTM) containing human pluripotent stem cell derived pancreatic precursors (progenitors) is actively accruing patients at our Alpha Stem Cell Clinic and has expanded to include another site at the University of Alberta in Canada. The trial has provided vital insights into mechanisms of impaired insulin production in type 1 diabetes. Studies to evaluate pancreatic progenitor differentiation and insulin production following implantation are ongoing. This study is supported by ViaCyte, Inc. and the Sanford Stem Cell Clinical Center.

Second, a first-in-human trial to evaluate safety and tolerability of a neural stem cell product for thoracic spinal cord injury has completed treatment of the first cohort of patients and will proceed to the second cohort. The trial has provided key insights into factors that promote neural stem cell regeneration in areas of injury. Proof-of-concept studies to evaluate neural repair and regeneration are ongoing. The protocol describing the plan to enroll the second cohort of patients at a higher cell dose is currently being evaluated by the FDA. This study is supported by Neuralstem Inc. and the Sanford Stem Cell Clinical Center.

Third, a phase 3 trial to establish efficacy of a mesenchymal stromal cell (MSC) product is currently being evaluated in patients with advanced congestive heart failure. As a result of Alpha Stem Cell Clinic involvement, accrual has increased on the trial at UC San Diego. Efficacy endpoints will be reported at the time of study completion. The trial is sponsored by Teva and has provided the impetus for a pipeline trial at the Alpha Clinic that will involve an innovative cellular imaging reagent for MRI developed by CIRM funded Professor Erich Ahrens and Nobel Laureate, Professor Roger Tsien (Nature Materials, March 14, 2016).

Finally, a first-in-human trial to evaluate the safety and tolerability of a CIRM funded antibody that targets an embryonic (Wnt5A) receptor, ROR1, which is re-expressed by a broad array of incurable malignancies is currently being tested in patients with relapsed or refractory chronic lymphocytic leukemia. The trial has provided important insights into Wnt5a/ROR1 mediated mechanisms of cancer stem cell survival and metastasis. The trial is actively accruing patients who will also have evaluation of biomarkers of response, including ROR1 internalization, lymph node size and absolute lymphocyte count measurements. Results from the Phase 1A trial have provided the impetus for the a Phase 1B extended dosing trial that is currently under review by our IRB and a Breast Cancer Research Foundation funded trial for advanced breast cancer in combination with Taxol that will be performed in our Alpha Stem Cell Clinic upon FDA approval of the IND. As a result of current phase 1 results, Cirmtuzumab development has been partnered with Oncternal Therapeutics Inc., a local biotechnology company, and through the CIRM Alpha Stem Cell Clinic for Phase 2 trials in advanced malignancies.