Presented by Ke-Yong Shi

2012.12.16

StemEx® ： from Research to

Clinical Trial

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.

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.

Modulation of cellular Cu by TEPA

effect on cell proliferation

Purified CD34+ cells were

cultured in 24-well Costar

Cell Culture Clusters at 104

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.

effect on cell proliferation

Other Metal Ions

effect on cell differentiation

effect on cell differentiation

Progenitor cell purification

research-grade CD34-based

separation device

clinical grade CD133-based

device.

Clinical-scale ex vivo expansion

Cultures were initiated with 1/104 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.

Clinical-scale ex vivo expansion

Evaluation of the expansion procedure

Evaluation of the expansion procedure

Evaluation of the expansion procedure

NOD/SCID engraftment potential of the expanded graft

NOD/SCID engraftment potential of the expanded graft

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.