Allogeneic hematopoietic stem cell transplantation (HSCT) has been performed globally for decades with curative intent in patients with a wide range of hematologic malignancies and rare genetic disorders. The procedure involves transferring hematopoietic cells sourced from a healthy donor to a patient following the administration of chemotherapy and/or radiation therapy. The biological properties of the various cell populations present in the allogeneic hematopoietic cell graft play an essential role in determining outcomes of HSCT.

Donor-sourced CD34+ cells have the unique ability to engraft and reconstitute a new blood and immune system, and donor-sourced immune cells, such as T cells, have an important protective role following HCT in eradicating residual cancer cells and providing protection against life-threatening infections. The engraftment of donor-sourced CD34+ cells is essential for successful reconstitution, and any delay in, or failure of, engraftment leaves a patient severely immuno-compromised and exposed to exceedingly high risk of early morbidity and mortality. Additionally, while the donor-sourced immune cells impart a critical immunotherapeutic effect, allo-reactive T cells can cause graft-versus-host disease (GvHD), a serious complication where donor-sourced T cells recognize antigens on a patient’s cells as foreign and attack the patient’s cells.

According to the Center for International Blood and Marrow Transplant Research, approximately 30,000 allogeneic HSCT procedures are performed globally each year. Hematopoietic cells for use in allogeneic HSCT can be obtained from multiple donor sources including umbilical cord blood, bone marrow and mobilized peripheral blood (mPB). Approximately 65% of allogeneic HSCT procedures utilize mPB as the donor hematopoietic cell source. While the use of mPB is associated with faster rates of neutrophil engraftment compared to other cell sources like bone marrow and umbilical cord blood, approximately 35-60% of patients undergoing mPB HSCT develop acute GvHD. Additionally, approximately 50% of patients undergoing HSCT experience cancer relapse or die within the first two years following HSCT. We believe our cell programming approach has the potential to reduce the three leading causes of morbidity and mortality associated with allogeneic HSCT – namely, GvHD and disease relapse – and to improve outcomes in patients undergoing allogeneic HSCT.

We are developing ProTmune as an investigational programmed cellular immunotherapy for use as a next-generation allogeneic HSCT cell graft. ProTmune is produced by modulating donor-sourced mPB ex vivo with two small molecules to enhance the biological properties and therapeutic function of the graft’s cells. The programmed mPB graft is administered to a patient as a one-time intravenous therapy. Based on preclinical data, we believe ProTmune has the potential to suppress the GvHD response and maintain the anti-tumor, or graft-versus-leukemia (GvL), activity of donor T cells. There are currently no FDA-approved therapies for the prevention of GvHD in patients undergoing allogeneic HSCT, giving rise to a significant unmet medical need.

We are conducting a multi-center Phase 1/2 clinical trial of ProTmune in adult subjects with hematologic malignancies undergoing mPB HSCT following myeloablative conditioning, a clinical trial which we refer to as the PROTECT study. The ongoing Phase 2 stage of the PROTECT study is a randomized, controlled and double-blinded clinical trial assessing the safety and efficacy of ProTmune in up to 80 adult subjects with hematologic malignancies undergoing matched unrelated donor HSCT following myeloablative conditioning. In November 2019, we reported that the Phase 2 stage of the PROTECT study had been fully enrolled.