TXA127 in Enhancement of Engraftment in Adult Double Cord Blood Transplantation

Cord blood as a hematopoietic stem cell source has multiple advantages. Cord blood is
normally discarded at birth and can easily be collected and stored. Availability of numerous
CB banks has resulted in genetically diverse CB units including those from non-Caucasians.
Once a suitable CB unit is located, confirmatory typing can be quickly performed and a donor
unit can be shipped to the transplant center. Furthermore, because a CB graft results in a
lower incidence of graft-versus-host-disease, one or two antigen-mismatched units are
acceptable for transplantation. Despite these advantages, CB has a significant drawback which
is that the number of hematopoietic stem cells obtained from a unit of CB is significantly
lower than from a bone marrow (BM) harvest or peripheral blood stem cell (PBSC) harvest. Both
engraftment and immune reconstitution are delayed in patients undergoing CB transplant.
TXA127 is pharmaceutically-formulated angiotensin 1-7, a non-hypertensive derivative of
angiotensin II (which contains the 8th amino acid conferring receptor binding to blood
pressure receptors). TXA127 has multilineage effects on hematopoietic progenitors in vitro
and in vivo. The hematopoietic properties demonstrated in preclinical and clinical studies
support the investigation of TXA127 to reduce time to neutrophil and platelet engraftment
following transfusion of limited number of CD34+ cells.

Inclusion Criteria:

- Subjects with Acute Myelogenous Leukemia (AML) past first remission, in first or
subsequent relapse, induction failure, or in first remission with high-risk for
relapse (with high-risk cytogenetics or presence of flt3 mutation or secondary
leukemia from prior chemotherapy)

- Myelodysplastic Syndrome or Myelofibrosis of intermediate or high-risk

- Acute Lymphoblastic Leukemia (ALL): Induction failure, fist complete remission with
Philadelphia chromosome or translocation (4:11), hypodiploidy and or evidence of
minimal residual disease by flow cytometry, second or third complete remission or
second relapse

- Chronic Myelocytic leukemia (CML): Second chronic phase or accelerated phase

- Non-Hodgkin's Lymphoma (NHL): Induction failures, second or third complete remission
or relapse

- Hodgkin's Lymphoma (HL): Induction failures, second or third complete remission or
relapse

- Chronic Lymphocytic leukemia (CLL): Progressive disease following standard therapy

- Other hematologic malignancies which meet investigational site standards for cord
blood transplant

- Subjects must be at least 18 years of age

- Subjects must have ECOG status of ≤ 2

- Subjects with bone marrow blasts ≤ 10%

- Subjects must have adequate major organ function

- Male and Female Subjects capable of reproduction must agree to use contraceptive
methods during the course of the study and for 2 months following the last
administration of study drug

- Cord blood requirements: a) Unrelated CB will be used as a source of hematopoietic
support if a 7/8 or 8/8 related or 8/8 unrelated bone marrow donor is not available,
or if the tempo of the subject's disease dictates it is not in the subject's best
interest to wait for an unrelated marrow donor to be procured. b) Subjects must have
two CB units available which are matched with the subject at 4/6, 5/6, or 6/6 HLA
class I (serological) and II (molecular) antigens. Each unit must contain at least 1 x
10^7 total nucleated cells/kg recipient body weight (pre-thaw).

Exclusion Criteria:

- Subjects who received antineoplastic treatment including chemotherapy, immunotherapy
and radiation therapy ≤ 2 weeks prior to Screening Period

- Subjects who underwent prior total body irradiation

- Subjects who received prior allogeneic hematopoietic cell transplants

- Subjects seropositive for HIV, Hepatitis B or Hepatitis C

- Female subjects who are pregnant or breastfeeding

- Subjects who have received an investigational drug within 30 days of projected first
administration of study drug (Day 0)

- Subjects with current alcohol use, illicit drug use, or any other condition (e.g.,
psychiatric disorder) that, in the opinion of the Investigator, may interfere with the
subject's ability to comply with the study requirements or visit schedule

- Subjects with known hypersensitivity to TXA127

- Subjects with uncontrolled medical or psychiatric condition which would limit informed
consent

- Subjects with a willing and appropriate HLA-matched related marrow donor