Efficacy Study of a TXA127 to Reduce Graft-vs-Host Disease in Subjects Undergoing Allogeneic Peripheral Blood Stem Cell Transplantation

Allogeneic hematopoietic stem cell transplantation (HSCT) is increasingly used as an
effective treatment for malignant disease. The three most common sources for stem cells used
in HSCT are bone marrow (BM), umbilical cord blood (UCB), and peripheral blood stem cells
(PBSC). In a retrospective review of 1,525 adults with acute leukemia receiving allogeneic
transplants between 2002 and 2006, UCB accounted for 10.8%, PBSC for 58.2%, and BM for 31%
of the population (Eapen et al., 2010). PBSC as a source of hematopoietic stem cells for
transplantation has advantages over bone marrow in terms of donation ease and comfort and
over cord blood in terms of adequate cell dose. However, PBSC transplantations are
associated with an increased incidence of graft-versus-host disease (GVHD). Based on
current literature acute GVHD (aGVHD) is reported in 48-80% of PBSCT recipients (Eapen et
al., 2010, Ferrara et al., 2009). Additionally, the myeloablative conditioning regimens
used for these transplants often result in mucositis which can be debilitating to patients.
TXA127 is pharmaceutically-formulated angiotensin 1-7, a non-hypertensive derivative of
angiotensin II. 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 the incidence of aGVHD and mucositis in this patient
population.

Inclusion Criteria:

- Provided written informed consent.

- ≥18 years of age.

- Meet institutional standard criteria for PBSC transplantation

- Myeloablative conditioning regimen

- Histologically confirmed diagnosis of a hematologic malignancy.

- Life expectancy of >4 months.

- Female subjects capable of reproduction (defined as a subject who has started menses)
must agree to the following: 1) Use of an effective oral or IM contraceptive method
during the course of the study and 2 months following the last administration of
Investigational Product; and 2) must have a negative pregnancy test result within 7
days prior to first Investigational Product dose.

Exclusion Criteria:

- Uncontrolled infection at the time of transplant.

- Pregnant or breastfeeding.

- Known to be seropositive for HIV or HTLV-1.

- Active CNS disease at the time of study enrollment.

- Treatment with an investigational agent within 30 days of anticipated administration
of the first dose of Investigational Product.

- 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.

- Any co-morbid condition which, in the view of the Principal Investigators, renders
the subject at too high a risk from treatment complications and regimen-related
morbidity/mortality.

- Prophylactic treatment with palifermin for mucositis.

- Subjects with a known sensitivity to any of the Investigational Product components.