JSP191

JSP191 (formerly AMG191) is a first-in-class humanized monoclonal antibody in clinical development as a conditioning agent to clear hematopoietic stem cells from bone marrow. It is designed to replace chemotherapy/radiation in patients undergoing curative hematopoietic stem cell transplantation and gene therapies.


Mechanism of action


A unique compound, JSP191 specifically binds to human CD117, a receptor for stem cell factor (SCF), which is expressed on the surface of hematopoietic stem and progenitor cells. The interaction of SCF and CD117 is required to maintain hematopoietic stem cells. JSP191 blocks SCF from binding to CD117 and disrupts critical survival signals, leading to the depletion of hematopoietic stem cells. This creates an empty space in the bone marrow for donor or gene-corrected transplanted cells to engraft. Because JSP191 does not carry a toxic payload or recruit immune cells to induce an immune response, the likelihood of off-target toxicities is significantly reduced.

 

Preclinical study results


Preclinical studies have shown that JSP191 as a single agent safely depletes hematopoietic stem cells, including in xenograft animal models of normal human blood formation and MDS.

 

Clinical development


To date, JSP191 has been evaluated in more than 80 healthy volunteers and patients.

It is currently being evaluated as a sole conditioning agent in an ongoing Phase 1 dose-escalation trial to achieve donor stem cell engraftment in patients undergoing hematopoietic cell transplantation for severe combined immunodeficiency (SCID). A severe genetic immune disorder, SCID leaves patients without a functioning immune system, and is curable only by this type of treatment. Initial results from the Phase 1 trial, presented in an oral session at the American Society of Hematology (ASH) 2019, showed that JSP191 safely cleared the bone marrow of hematopoietic stem cells and allowed successful engraftment of donor stem cells. All patients showed evidence of hematopoietic stem cell engraftment and clinical benefit, and no treatment-related toxicities were observed.

JSP191 is also being evaluated as a conditioning agent in an open-label, multicenter Phase 1/2 study in patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) who are undergoing hematopoietic cell transplantation.