Jasper Therapeutics announces clinical data from Phase I/II trial of briquilimab

Jasper Therapeutics announced clinical data from the first three participants in an investigator-initiated Phase 1/2 clinical trial evaluating the addition of briquilimab, Jasper’s anti-c-KIT monoclonal antibody, to an existing bone marrow transplantation regimen in individuals with sickle cell disease and beta thalassemia considered at high risk for complications from or ineligible for standard myeloablative hematopoietic stem cell transplant. The addition of briquilimab is being studied as a potential way to achieve a higher percentage of healthy donor stem cell engraftment without increased toxicity. The Phase 1/2 clinical study is led by Dr. John F. Tisdale, Director of the Cellular and Molecular Therapeutics Laboratory, NHLBI. For SCD and beta-thalassemia, transplantation of healthy donor stem cells is a multi-step process. After donor cells are collected, a human subject’s existing stem cells must be cleared from the bone marrow to make space for the transplanted cells, which is known as bone marrow conditioning. Next, the newly transplanted cells must survive and replicate within the bone marrow, which is known as bone marrow engraftment. The extent of engraftment is measured by the proportion of the donor cells and the human subject’s own cells, which is known as donor chimerism. As has been shown, improving chimerism is crucial to lead to a sufficient proportion of healthy donor stem cells that produce healthy red blood cells and reverse the sickle phenotype after the stem cell transplant. The primary objective of the study is to determine if the addition of briquilimab would increase the proportion of patients with donor myeloid chimerism greater than or equal to98% at 1-year post-transplant. Briquilimab has the potential to improve disease-free survival in combination with low-dose irradiation as part of a transplant conditioning regimen. The study is currently actively enrolling at NHLBI. In this study, briquilimab was added to the regimen used at NHLBI consisting of alemtuzumab, low-dose irradiation, and sirolimus prior to infusion of mobilized peripheral blood cells from human leukocyte-antigen matched related donors. All three sickle cell study participants treated with briquilimab have successfully engrafted with no briquilimab-related severe adverse events observed. Participant 1 achieved neutrophil engraftment at 12 days after transplant and platelet engraftment at 17 days after transplant. Participant 2 achieved neutrophil engraftment at 12 days and platelet engraftment at 10 days. Participant 3 achieved neutrophil engraftment at 16 days and platelet engraftment at 8 days. Both of the first two participants with peripheral blood chimerism achieved 100% donor myeloid chimerism at 60 days post-transplant. At five months post-transplant, the first participant treated with briquilimab has a total hemoglobin of 13.3 g/dL, increased from 8-9 g/dL at baseline.