Change in drug product development strategy

The purpose of this study is to evaluate the efficacy of TXA127 to reduce the incidence (Grade II-IV) of acute Graft-vs.-Host Disease (aGVHD) in adult subjects undergoing double umbilical cord blood transplantation (UCBT). The study will also evaluate the effects of TXA127 on incidence, severity and duration of mucositis; neutrophil engraftment and platelet recovery; platelet transfusion requirements; immune reconstitution; and duration of corticosteroid use. TXA127 has shown to be well tolerated by patients and appears to induce rapid production of neutrophils and platelets in the bloodstream, as well as increase the immune system components. TXA127 has also been shown reduce the severity of chemotherapy-induced mucositis.

Cord blood (CB) 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 (GVHD), one or two antigen-mismatches may be acceptable for transplantation. Despite these advantages, CB has a significant drawback: the number of hematopoietic stem cells obtained from a unit of CB is significantly lower than from a bone marrow (BM) or peripheral blood stem cell (PBSC) harvest. The number of stem cells can be increased by transplanting two cord blood units, however the incidence of GVHD increases in patients receiving two CB units compared to patients who receive one unit. Another issue in this population is mucositis, as a result of myeloablative conditioning given prior to the transplant, which can be debilitating to patients. 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 the incidence of acute GVHD (aGVHD) and mucositis in this patient population.

Inclusion Criteria:

• Provided written informed consent.
• ≥18 years of age.
• Meet institutional standard criteria for double UCB 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.