1. Presented by Ke-Yong Shi 2012.12.16 StemEx ® from Research to Clinical Trial

2. Background Each year, approximately 60,000 patients with leukemia or lymphoma need a bone marrow transplantation. Of these, only approximately 25,000 are transplanted, primarily because the other 35,000 are unable to find a fully matched bone marrow donor. Cord blood transplantation (CBT) does not require full tissue matching and is considered a good alternative for transplantation. CBT is limited by a low number of TNC and CD34 + cells, Ex-vivo expansion is a strategy employed to increase the number of stem/progenitor cells and improve clinical outcomes.

3. Question? Metal ions such as Fe, Ca, Mg, and Zn are known to play important roles in basic cell functions such as cell survival, proliferation, and differentiation. Cu deficiency is often associated with hematopoietic cell differentiation arrest, which results in anemia, neutropenia, and thrombocytopenia. the role of Cu? Zidar BL, et al. Am J Hematol. 1977;3:177–185. Hirase N, et al. Acta Haematol. 1992;87:195–197. Banno S, et al. Rinsho Ketsueki. 1994;35:1276–1281.

4. Modulation of cellular Cu by TEPA

5. effect on cell proliferation Purified CD34 + cells were cultured in 24-well Costar Cell Culture Clusters at 10 4 cells/ml in alpha medium supplemented with 10% FBS and the following human recombinant cytokines: TPO, IL-6 and FLT-3, at final concentration of 50 ng/ml each, and IL-3 at 20 ng/ml.

6. effect on cell proliferation

7. Other Metal Ions

8. effect on cell differentiation

10. Progenitor cell purification research-grade CD34-based separation device clinical grade CD133-based device.

11. Clinical-scale ex vivo expansion Cultures were initiated with 1/10 4 cells/mL, grown in 290 mL culture bags (initial culture volume/bag, 25 mL) in alpha medium supplemented with FCS, a combination of four cytokines (SCF, TPO, IL-6 and FLT-3 ligand, 50 ng/mL each) and 5 mm TEPA.

12. Clinical-scale ex vivo expansion

13. Evaluation of the expansion procedure

16. NOD/SCID engraftment potential of the expanded graft

19. StemEx® StemEx is a graft of stem/progenitor cells isolated and expanded from a portion of a single unit of umbilical cord blood (CBU) and transplanted in combination with non-expanded cells from the same unit. The market potential of StemEx is estimated at more than one billion USD. StemEx is now being Phase III pivotal registration clinical trial. Safety and efficacy clinical outcomes of the study will be available in Q4/2012.