Allogeneic SCT of NiCord®, UCB-Derived Ex Vivo Expanded Stem and Progenitor Cells, in Patients With Hemoglobinopathies

Umbilical cord blood (UCB) is an alternative stem cell source for hematopoietic stem cell
transplantations (HSCT) and can be used for the treatment of various life-threatening
diseases, such as hematological malignancies or genetic blood disorders, in such cases where
a matched related stem cell donor is not available. However, the major drawback of using this
valuable stem cells source is the limited cell dose in a single cord blood unit (CBU), which
was shown to be associated with inadequate hematopoietic reconstitution and high risk of
transplant-related mortality. To improve outcomes and extend applicability of UCB
transplantation, one potential solution is ex vivo expansion of UCB-derived stem and
progenitor cells. NiCord® is a stem/progenitor cell based product composed of ex vivo
expanded allogeneic UCB cells. NiCord® is based on a novel technology for the ex vivo cell
expansion of cord blood derived hematopoietic progenitor cells. By increasing the number of
the short and long-term reconstitution progenitor cells transplanted, NiCord® has the
potential to enable the broader application of UCB transplantation, and improve the clinical
outcomes of UCB transplantation.

In Part 1 of this study, NiCord® will be administered to the patient in conjunction with a
second, unmanipulated CBU. In Part 2 of this study, NiCord® will be administered to the
patient without a second, unmanipulated CBU. The study duration per patient is approximately
270 days from signing of informed consent to last visit on day 180 post-transplant.

The overall study objectives of part 1 of this study are to evaluate the safety and efficacy
of co-transplantation of NiCord® and an unmanipulated CBU in patients with Hemoglobinopathies
(Sickle Cell Disease (SCD), or thalassemia major) following myeloablative therapy. The
overall study objectives of part 2 of this study are to evaluate the safety and efficacy of
transplantation of NiCord® in patients with Hemoglobinopathies (Sickle Cell Disease (SCD), or
thalassemia major) following myeloablative therapy.

The study hypothesis for part 1 of this study is that the co-transplantation of NiCord® and
an unmanipulated unrelated cord blood graft in patients with hemoglobinopathies (SCD, or
thalassemia major) following myeloablative preparative therapy will be safe and will enable
cord blood engraftment. The study hypothesis for part 2 of this study is that transplantation
of NiCord® in patients with hemoglobinopathies (SCD, or thalassemia major) following
myeloablative preparative therapy will be safe and will enable cord blood engraftment.

Up to fifteen (15) evaluable patients recruited for part 1 of the study and up to five (5)
patients for part 2 of the study should be 2-45 years of age, at least 10 kg in weight, have
symptomatic SCD or thalassemia major and should be considered as candidates for allogeneic
myeloablative HSCT for the treatment of SCD.

Inclusion Criteria:

- Must be 2 - 45 years of age and at least 10 kg

- Must have clinically severe SCD (SS, SC or SBeta0 Thal) or thalassemia major and be
eligible for myeloablative SCT

- Must have two partially HLA-matched CBUs for part 1; and one partially HLA-matched CBU
for part 2

- Back-up autologous stem cells harvested from bone marrow

- Adequate Karnofsky Performance score or Lansky Play-Performance scale

- Sufficient physiological reserves

- Signed written informed consent

Exclusion Criteria:

- HLA-matched related donor able to donate

- Severe alloimmunization with inability to guarantee a supply of adequate PRBC donors

- Prior allogeneic hematopoietic SCT within the last 12 months or reduced-intensity
transplant within the past 6 months

- Human immunodeficiency virus (HIV) infection

- Active or uncontrolled infection

- Pregnancy or lactation