In a press release dated April 29, 2021, we reported positive topline Phase I results in our innovative hematology program. This study, the first to evaluate PLX-R18 in humans, demonstrated that PLX-R18 had the potential to stimulate the bone marrow to generate all three blood cell lines – a meaningful advantage over other existing and proposed treatments.
Blood disorders can be very challenging to manage. Consider, for example, a cancer patient suffering from Acute Lymphoblastic Leukemia (ALL), who is receiving a Hematopoietic Cell Transplantation (HCT). While the transplant itself can improve his chances of survival from the cancer, there is a potential risk of poor graft function resulting in incomplete hematopoietic recovery leaving the patient with a life-threatening condition. Between 5-10% of all HCT recipients suffer from poor graft function (source: Chen 2020).
While standard-of-care treatments may temporarily improve blood counts, patients that continuously fail to maintain satisfactory blood counts may remain vulnerable to bleeding and recurrent infections. These patients will require repeated, costly blood transfusions, which are, unfortunately, only a short-term solution.
Therefore, we believe that there is a need for long-lasting treatment that has the potential to support generation of all three blood lines, red blood cells, white blood cells and platelets, thereby alleviating the dependency on blood transfusions and medications. Current standard of care does not address all three blood lines at once. Rather, patients suffering from sub-optimal bone marrow recovery may need to receive multiple treatments to address each deficiency.
Our PLX cells are derived from placentas that have been donated by women after birth. The PLX cells release a range of therapeutic proteins that trigger the body’s regenerative mechanism in response to severe medical conditions. PLX-R18 is the first product candidate manufactured using Pluri’s proprietary serum-free media in a 3-D bioreactor system, displaying our unique capability to manufacture a high quantity of cells with batch-to-batch consistency. Created from cells that originated from the fetus side of the placenta, PLX-R18 is unique in its potential to support renewal and differentiation of hematopoietic cells.
Our hematology program tested the use of PLX-R18 in HCT recipients. We were pleased to find that the PLX-R18 showed promising results. The study enrolled 21 patients in the U.S. and Israel, who were at least three months after the HCT procedure (median: 236 days) and had low blood counts in at least one blood cell lineage. They were assigned to one of three treatment arms: 1 million cells/kg, 2 million cells/kg, or 4 million cells/kg. Each patient received two treatments of the assigned dose.
The results, which included data from 14 of the 21 patients*, demonstrated that PLX-R18 had the potential to stimulate the implanted hematopoietic cells to realize their therapeutic potential and generate improved blood counts over the long term in all three blood cell lines at once – a meaningful advantage over other existing and proposed treatments. Overall, PLX-R18 was well tolerated and showed significant improvements from baseline counts in all cohorts for hemoglobin and platelet counts. Interestingly, patients in the high-dose category exhibited statistically significant improvements in all three blood cell lines.
Pluri’s Chief Medical Officer, Nitsan Halevy, believes that these results are an important step for the science of blood, or hematology. PLX-R18’s proposed hematopoietic mechanism of action, now demonstrated for the first time in humans in our Phase I HCT study, potentially opens up new therapeutic options in the fields of hematology. Building on these encouraging initial results, Pluri is refining its clinical development plans for PLX-R18 to address areas of unmet medical need.
* Data from the six-month follow-up is available for 14 of the 21 treated patients: one patient was terminated early, three patients missed the 6-month visit and three died prior to the 6-month visit (two fatal events in the 2 million cell dose, and one fatal event in the 4 million cell dose). All fatal events in the study were considered unrelated to the study treatment. Mortality rates were in line with publicly available information (references: Gao et al 2020, Halahleh et al 2021, Tang et al 2018, Sun et al. 2015, Zhao et al 2019)