REDWOOD CITY, Calif.—Jasper Therapeutics Inc. has reported positive preliminary findings from its ongoing multicenter Phase 1 clinical trial of JSP191, a first-in-class anti-CD117 monoclonal antibody, as a conditioning agent in older patients with myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) undergoing hematopoietic cell transplantation. The findings were presented as a late-breaking abstract at the 2021 Transplantation & Cellular Therapy Meetings of the American Society for Transplantation and Cellular Therapy, and the Center for International Blood & Marrow Transplant Research.
A Phase 1 study (JSP-CP-003) is evaluating the safety, tolerability, and efficacy of adding JSP191 to the standard conditioning regimen of low-dose radiation and fludarabine among patients age 65 to 74 years with MDS or AML undergoing hematopoietic cell transplantation. Patients were ineligible for full myeloablative conditioning. The primary outcome measure of the study is the safety and tolerability of JSP191 as a conditioning regimen up to one year following a donor cell transplant.
Data from the first six patients who received a single dose of JSP191 prior to transplantation showed successful engraftment in all six patients. Complete donor myeloid chimerism (equal to or greater than 95 percent) was observed in five of six evaluable patients at 28 days, and three patients had complete donor chimerism observed at day 90. Three of five evaluable patients showed complete eradication of measurable residual disease (MRD) at 28 days, as measured by next-generation sequencing, and two patients showed substantial reductions in MRD. No treatment-related serious adverse events have been reported to date.
“These early clinical results are the first to demonstrate that JSP191 administered in combination with a standard non-myeloablative regimen of low-dose radiation and fludarabine is well tolerated, and can clear measurable residual disease in older adults with MDS or AML undergoing hematopoietic cell transplantation—a patient population with historically few options,” stated Dr. Kevin N. Heller, executive vice president of research and development at Jasper. “These patients could be cured by hematopoietic cell transplantation, but the standard-of-care myeloablative conditioning regimens used today are highly toxic and [are] associated with high rates of morbidity and mortality, particularly in older adults.”
“Jasper is committed to developing safer, more effective conditioning agents to allow for expanded use of curative therapy with stem cell transplants and gene therapies,” says Bill Lis, chairman and CEO of Jasper. “We have a targeted approach to solve this challenge in JSP191, a first-in-class humanized monoclonal antibody in clinical development as a conditioning agent to clear hematopoietic stem cells from bone marrow. JSP191 is designed to replace chemotherapy/radiation in patients undergoing curative HSC transplantation and gene therapies.”
“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. JSP191 blocks SCF from binding to CD117 and disrupts critical survival signals, leading to the depletion of HSCs,” Lis explains. “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.”
“JSP191 was designed to bind tightly to CD117 with picomolar affinity and to provide two key therapeutic properties: inhibit SCF binding and function as a neutral antagonist that does not degranulate mast cells,” adds Heller. “These attributes allow JSP191 to be used as a monotherapy or in synergistic combination with other modalities to deplete normal and diseased stem cells without risk of severe hypersensitivity immune response ... And because it is an aglycoslyated humanized IgG1 anti-human antibody, there is no significant effect on mast cells or germ cells. The mechanism of action of JSP191 is also synergistic with radiation, azacytidine and CD47.
“Traditional lower intensity transplant conditioning regimens are better tolerated in older adults, but are associated with higher rates of relapse in MDS/AML patients with measurable residual disease. JSP191 ... has the potential to be a curative option for these patients.”
“JSP191 is intended to be used both as a single agent and in combination with low-dose irradiation or 5-azacitidine ... JSP191 is [also] being evaluated as a sole conditioning agent in an ongoing Phase 1/2 trial to achieve donor stem cell engraftment in patients undergoing hematopoietic cell transplantation for SCID [severe combined immunodeficiency],” Heller and Lis note.
“In the ongoing Phase 1/2 SCID clinical trial, JSP191 has demonstrated the ability to create HSC niche space in the bone marrow when evaluated in patients in a re-transplant and first transplant setting. Twelve previously transplanted patients have been treated to date. Results have shown JSP191 to be safe and effective in depleting recipient HSC, permitting engraftment of donor HSC. Because JSP191 has been shown to be well tolerated, the patients remaining in the first cohort of patients will undergo most of the transplant procedure in the outpatient setting, and the study is now open to infants,” points out Heller. “Clinically, patients in the trial have shown resolution of chronic infections, independence from IVIG, and antibody response to vaccine challenge.”
“In addition to [the AML/MDS and SCID] clinical trials, a pilot study of JSP191 in autoimmune diseases is planned for the second half of 2021, an investigator-sponsored trial in patients with Fanconi anemia is being conducted at Stanford, and Jasper has announced recent partnerships to study JSP191 conditioning for X-SCID gene therapy with Graphite Bio, and for sickle cell disease with the National Heart, Lung, and Blood Institute (NHLBI) of the NIH,” he concludes.