Transplantation of Ex Vivo Expanded, UCB-derived, Stem & Progenitor Cells vs. Unmanipulated UCB for HM Patients

Successful blood and marrow transplantation (BMT) requires the infusion of a sufficient
number of hematopoietic stem/progenitor cells (HSPCs), capable of both homing to the bone
marrow and regenerating a full array of hematopoietic cell lineages with early and late
repopulating ability in a timely fashion.

A major drawback of Umbilical Cord Blood (UCB) is the low stem cell dose available for
transplantation, compared to mobilized peripheral blood (PB) or bone marrow. This low stem
cell dose can compromise the chances of engraftment and contributes to delayed kinetics of
neutrophil and platelet recovery, as well as other transplant outcomes.

The aim of ex vivo expansion of cord blood is to provide a graft with sufficient numbers of
cells that have rapid and robust in vivo neutrophil and platelet producing potential to
enable successful transplantation.

NiCord® is a stem/progenitor cell-based product composed of ex vivo expanded allogeneic cells
from one entire unit of UCB. NiCord® utilizes the small molecule nicotinamide (NAM), as an
epigenetic approach to inhibit differentiation and to increase the migration, bone marrow
(BM) homing and engraftment efficiency of Hematopoietic Progenitor Cells (HPC) expanded in ex
vivo cultures. The chief aim of the study is to compare the safety and efficacy of NiCord®
single ex-vivo expanded cord blood unit transplantation to unmanipulated cord blood unit
transplantation in patients with hematological malignancies following conditioning therapy.

Inclusion Criteria:

- Applicable disease criteria

- Patients must have one or two partially HLA-matched CBUs

- Back-up stem cell source

- Adequate Karnofsky/Lansky Performance score

- Sufficient physiological reserves

- Signed written informed consent

Exclusion Criteria:

- HLA-matched donor able to donate

- Prior allogeneic HSCT

- Other active malignancy

- Active or uncontrolled infection

- Active/symptoms of central nervous system (CNS) disease

- Pregnancy or lactation