PROHEMA FOR HEMATOLOGIC MALIGNANCIES
Our lead product candidate, ProHema, seeks to enable the curative potential of umbilical cord blood as a cell source for HSCT for a broad spectrum of life-threatening malignant disorders. ProHema is an ex vivo programmed hematopoietic cellular therapeutic derived from umbilical cord blood which has been optimized to enhance the therapeutic potential of hematopoietic cells. ProHema is produced through a proprietary, two-hour, ex vivo programming process using a small molecule modulator (FT1050, also known as dmPGE2, a stable derivative of prostaglandin E2) that promotes rapid and supra-physiologic activation of genes involved in the homing, proliferation and survival of HSCs, which are key biological properties necessary for durable engraftment and hematopoietic reconstitution.
Preclinical and early clinical findings indicate that ProHema may promote both neutrophil engraftment and immune reconstitution following HSC transplantation. In an initial Phase 1b clinical trial in adult patients with hematologic malignancies undergoing double umbilical cord blood transplant (dUCBT), the median time to neutrophil recovery (> 500 cells/µL) with ProHema was 17.5 days, which compares favorably to historical norms for patients undergoing dUCBT, and 100-day survival with ProHema was 100%.In addition, an analysis of the CD8+ T cell compartment of patient samples from our Phase 1b clinical trial revealed that, at Day 100, subjects who received ProHema showed a two-fold increase in the percentage of naïve and early memory T cell fraction within the CD8+ T cell compartment, as compared to subjects who received two unmanipulated cord blood units. These naïve and early memory CD8+ T cell populations are believed to play a key role in promoting immune reconstitution and viral immunity following cord blood transplantation. Consistent with these reported immuno-modulatory effects on CD8+ T cells, low rates of viral reactivation were observed in our Phase 1b clinical trial. Specifically, cytomegalovirus (CMV) reactivation occurred in only two of 12 ProHema subjects, which compares favorably to rates of CMV reactivation reported in the literature
ProHema in Adult Hematologic Malignancies: Phase 2 PUMA Study
The PUMA study (ProHema in UMbilical cord blood transplantation in Adults) is an ongoing, open-label, randomized, controlled, multi-center Phase 2 clinical trial designed to enroll 60 subjects, age 15 to 65 years, with hematologic malignancies. Patients are being randomized at a ratio of 2:1, with approximately 40 patients receiving ProHema plus an unmanipulated cord blood unit and approximately 20 patients receiving two unmanipulated cord blood units. At the discretion of the treating physician, patients are being conditioned using an intensive myeloablative or a reduced intensity regimen. The primary endpoint of the PUMA study is the cumulative incidence of neutrophil engraftment as compared to a pre-specified control median. Secondary endpoints include additional measures of neutrophil and platelet engraftment, rates of graft failure, acute graft versus host disease (GvHD) and serious infection, disease-free survival, and overall survival. We expect data on the primary efficacy endpoint from the Phase 2 PUMA study to be available in the second half of 2015.
In December 2014, the PUMA study’s independent Data Monitoring Committee (iDMC) conducted its second of two scheduled interim safety reviews of ProHema. A total of 20 subjects, including 12 subjects that received ProHema and eight control subjects were included in the interim review, which assessed safety, time to engraftment, rate of graft failure, early mortality, infection and graft versus host disease. Based on its consideration of the data available on the first 20 subjects as well as historical outcomes reported from multi-center clinical experiences, the iDMC determined that ProHema had met established safety criteria and supported continuation of the PUMA study.
Of the first 12 subjects administered ProHema in the Phase 2 PUMA study, 10 subjects received myeloablative conditioning (MAC) and two subjects received reduced-intensity conditioning (RIC). Eight of 10 ProHema subjects receiving MAC achieved neutrophil engraftment, with a median time of engraftment of 20 days. One of two ProHema subjects receiving RIC achieved neutrophil engraftment, which was reached on Day 14. Historical median times of neutrophil engraftment are approximately 26 days for patients receiving MAC and 21 days for patients receiving RIC based on multi-center reports published in the literature of adult patients undergoing double umbilical cord blood transplantation in the United States.
ProHema in Pediatric Hematologic Malignancies: Phase 1 PROMPT Study
In the US alone, over 3,500 children are diagnosed with leukemia each year, many of whom ultimately require HSC transplantation. For pediatric patients, the standard of care in umbilical cord blood transplantation for the treatment of hematologic malignancies utilizes a single cord blood unit. While the cell dose received by a pediatric patient from a single cord blood unit can be sufficient, data suggest that pediatric patients undergoing sUCBT are at high risk for experiencing delayed engraftment, graft failure and transplant‑related morbidity and mortality
The PROMPT study (ProHema for the treatment of hematologic Malignancies in PediaTric patients) is currently enrolling patients and is designed to evaluate ProHema in pediatric patients undergoing single umbilical cord blood transplantation (sUCBT) for the treatment of various hematologic malignancies, such as acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), following myeloablative conditioning. The study is being conducted at leading U.S. pediatric transplant centers, and will enroll up to 18 patients. The primary endpoint of the PROMPT study is safety as assessed by neutrophil engraftment. The study will also evaluate various parameters of efficacy, including additional measures of platelet engraftment, rates of graft failure, GvHD and serious infection, disease-free survival and overall survival. Data on the primary endpoint is expected in the second half of 2015.