Pilot Study Evaluating Safety & Efficacy of DCBT: NiCord® & UNM CBU to Patients With Hematological Malignancies

Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative procedure
for various hematological malignancies, bone marrow failure syndromes and inherited metabolic
disorders. The application of allogeneic HSCT is limited by donor availability such that only
approximately one-third of the otherwise appropriate candidates have suitably matched family
donors. Alternative donors include mismatched family members or matched unrelated donors, but
these approaches are often complicated by an increased risk of graft-versus-host disease
(GvHD) and a prolonged and cumbersome search and procurement process. In addition, far fewer
subjects of racial minorities find suitable human leukocyte antigen (HLA)-matched donors.

Umbilical cord blood has been increasingly used as an alternative source of stem cells and
has extended the availability of allogeneic HSCT to patients who would otherwise not be
eligible for this curative approach. In the last decade the number of cord blood
transplantations from related and unrelated donors has increased dramatically. It is
estimated that more than 20,000 patients have undergone cord blood transplantation from
unrelated donors to date for a variety of genetic, hematological, immunological, metabolic
and oncologic disorders. The major advantages of cord blood transplantation include easy
procurement, no risk to donors, reduced incidence of transmitting infections, immediate
availability, and reduced risk of acute GvHD in the setting of donor-recipient HLA mismatch.
Nevertheless, the low cell dose remains a main limitation of this cell source leading to
delayed hematopoietic reconstitution, higher risk of graft failure and relatively high
treatment related mortality rates as compared to other hematopoeitic cell sources. To improve
outcomes and extend applicability of cord blood transplantation, one potential solution is ex
vivo expansion of cord blood-derived stem and progenitor cells.

The Sponsor has undertaken to develop NiCord®, which is based on a novel technology for 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 broader application of umbilical cord blood transplantation and
improve clinical outcomes in subjects with high-risk hematological malignancies.

The main objective of the current study is to evaluate the safety of co-transplantation of
NiCord® and an unmanipulated cord blood unit in patients with hematological malignancies
following myeloablative therapy.

Inclusion Criteria:

- Applicable disease and eligible for myeloablative SCT

- Patients must have two partially HLA-matched CBUs

- Back-up stem cell source

- 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

- Prior allogeneic HSCT

- Lymphoma patients with progressive disease

- Other active malignancy

- Human immunodeficiency virus (HIV) infection

- Active or uncontrolled infection

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

- Pregnancy or lactation