New Stem Cell Transplant Strategy Appears Promising for Fanconi Anemia

International Congress on Targeted Therapies in Cancer®International Congress on Targeted Therapies in Cancer® October 2022
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The humanized monoclonal antibody JSP191 showed an 100% complete donor chimerism and resulted in no treatment-related adverse events when administered to patients with Fanconi anemia.

The first 2 patients with Fanconi anemia treated with JSP191 achieved 100% donor chimerism, and JSP191 safe to infuse with no treatment-related adverse events (AEs) or toxicities observed, according to findings of a phase 1/2 clinical trial (NCT04784052) announced by Jasper Therapeutics, Inc.1

JSP191 is a humanized monoclonal antibody currently in clinical development to work as a conditioning agent which will block stem cell factor receptor signaling and lead to clearance of hematopoietic stem cells from bone marrow. In turn, this will create an empty space for donor or genetically modified transplanted stem cells to engraft.

These positive clinical data were presented at the European Society of Blood and Marrow Transplantation, held on September 23-25, 2022, in Paris, France. Here, 100% complete donor chimerism was achieved at 6 months for the first patient and at 1 month for the second. Further, neutrophil engraftment was achieved on day 11 for both patients and platelet engraftment on days 9 and 14.

“Initial data from this study suggest that a conditioning regimen that includes JSP191 has the potential to achieve successful donor transplant with no JSP191-related adverse events or toxicities reported to date. The positive update presented gives us increased confidence in JSP191, which has now shown promise as a conditioning agent in 4 indications including acute myeloid leukemia, myelodysplastic syndromes, severe combined immunodeficiency, and Fanconi anemia,” said Ronald Martell, president, and chief executive officer of Jasper Therapeutics, in the press release. We look forward to continuing support for Stanford’s investigation of JSP191 and advancing our broader pipeline for JSP191 to the next phase of development.”

The phase 1/2 clinical trial aims to develop a cell therapy for Fanconi anemia with the hopes of causing fewer side effects than chemotherapy which is currently the current standard of care method for conditioning in this patient population.2

In the experimental arm, patients were given an infusion of donor stem cells which were depleted of αβ+T cells using the CliniMACS System device. Prior to stem cell transplant, patients received a reduced-intensity preparative regimen containing JSP191 in combination with rabbit anti-thymoglobulin (rATG), cyclophosphamide, fludarabine and rituximab (Rituxan).

Those eligible for enrollment in the trial were patients aged 2 years and older with a diagnosis of Fanconi anemia as demonstrated by abnormal chromosome breakage studies with increased sensitivity to mitomycin-C or diepoxybutane, at least 1 mutation in a known Fanconi-associated gene, bone marrow failure, and a life expectancy of at least 2 years. Patients of childbearing potential must use an effective contraceptive method during the time of peri-transplant conditioning through hematopoietic recovery.

Primary end points of the trial included the number of participants without grade 3 or 4 treatment emergent AEs, number of those able to achieve donor engraftment, and the number of patients who are able to have donor engraftment and the same rate or better vs the alternative hematopoietic cell transplant regimens for this patient population.

The secondary end points of the trial were serum concentration of JSP191, rATG, and fludarabine, participants who do not develop mucositis or veno-occlusive disease, number of participants who achieve hematopoietic recovery, donor engraftment, and immunologic recovery, the number of patients who develop grade I-IV acute or chronic graft-vs-host disease, and the number of participants who achieve disease-free survival.

Jasper Therapeutics, Inc, is now planning a new study of JSP191 as a second-line therapy option in lower-risk patients with MDS which will take place in 2022, as well as a pivotal study in AML/MDS transplant in early 2023. Additional studies have planned enrollment for patients with chronic granulomatous disease and GATA2 MDS who are undergoing hematopoietic cell transplantation as well as a study of JSP191 as a chronic therapeutic for low to intermediate risk patients with MDS.

“Patients affected by Fanconi anemia have increased sensitivity to conventional conditioning regimens and radiation due to innate defects in DNA repair. JSP191 offers a targeted conditioning strategy that eliminates the need for radiation or alkylating agents like busulfan,” said Martell in the press release.

  1. Jasper therapeutics announces positive clinical data from investigator sponsored study of JSP191 conditioning in Fanconi anemia patients at IEWP annual meeting. News release. Jasper Therapeutics, Inc. September 26, 2022. Accessed September 26, 2022.
  2. Depleted donor stem cell transplant in children and adults with fanconi anemia after being conditioned with a regimen containing JSP191. Updated February 18, 2022. Accessed September 26, 2022.
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