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Briquilimab improves success of stem cell transplant in 3 patients

Jasper Therapeutics’ investigational conditioning therapy briquilimab safely improved the success of stem cell transplants for three people with sickle cell disease (SCD), early Phase 1/2 trial data suggest.

Stem cell transplant success was observed in all three patients treated with briquilimab, plus a less-aggressive non-myeloablative conditioning regimen, which uses low-dose radiation combined with immunosuppressive medicines.

The success of stem cell transplantation is gauged by the achievement of 100% donor myeloid chimerism, which is the proportion of donor myeloid stem cells that give rise to red blood cells, white blood cells, and platelets.

All three patients also saw a marked rise in their levels of hemoglobin — the protein that carries oxygen in red blood cells — at their most recent follow-up.

Data presented at recent meeting on transplantation and cellular therapy

The findings were presented at the recent 2023 Tandem Meetings: Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR by John Tisdale, MD, the study lead and director of the Cellular and Molecular Therapeutics Laboratory at the National Heart, Lung, and Blood Institute, which also sponsored the study.

“We are encouraged by the continued positive data from this important study led by Dr. Tisdale and the National Institutes of Health for a high unmet need population,” Ronald Martell, Jasper’s president and CEO, said in a press release.

People with SCD produce a faulty version of hemoglobin, which causes normally oval-shaped red blood cells to take on a sickle-like shape. These misshapen red blood cells can block blood flow, affect oxygen delivery to tissues and organs, and lead to episodes of sudden and severe pain called vaso-occlusive crises.

Stem cell transplant has potential to cure sickle cell disease and beta thalassemia
A stem cell transplant can potentially cure both SCD and beta thalassemia, another blood disorder marked by a hemoglobin deficiency. However, bone marrow conditioning — a procedure that eliminates the patient’s faulty blood-forming stem cells to allow the transplanted healthy stem cells to survive and grow — is required before the transplant.

Myeloablative conditioning regimens typically use chemotherapy and radiation therapy to eliminate faulty stem cells. These aggressive and toxic regimens can cause serious side effects in vulnerable patients. On the other hand, non-myeloablative conditioning regimens use low-dose radiation combined with immunosuppressive medicines to improve the success of the transplant without the harmful effects of myeloablative conditioning treatments.

Briquilimab (formerly known as JSP191) is an antibody-based therapy targeting CD117 (also called c-Kit), a protein receptor on the surface of blood stem cells that is necessary for their survival. By binding to CD117 and disrupting survival signals, briquilimab is specifically designed to help clear patients’ faulty blood-forming stem cells before the transplant.

“There is significant room for improving outcomes for curative therapies in sickle cell disease through targeted antibody-based conditioning for both stem cell transplant as well as gene therapy,” Martell said.

An ongoing Phase 1/2 trial (NCT05357482) is investigating whether adding briquilimab to a non-myeloablative conditioning regimen can improve donor myeloid chimerism by 98% or more one year after transplant in patients with SCD or beta thalassemia.

Building on preliminary data on these three SCD patients, Jasper reported that 100% donor myeloid chimerism occurred at day 100 (about three months) in two SCD patients and after 30 days in the third.

In all three patients, hemoglobin levels before the transplant were 8-10 grams per deciliter (g/dL), below the normal range of 13.8-17.2 g/dL in men and 12.1-15.1 g/dL in women. At the most recent follow-up, hemoglobin levels rose to 12.6 g/dL in one of the patients, to 11.4 g/dL in another, and to 14 g/dL in the third.

No evidence of serious adverse events
There was no evidence of graft-versus-host disease, where donated cells attack cells in the recipient’s body, or briquilimab-related severe adverse events.

“Since initially reporting on this investigator-initiated Phase 1/2 clinical trial in January 2023, we are pleased to observe in this updated dataset that directly targeting c-Kit with our monoclonal antibody, briquilimab, has resulted in the first two SCD participants achieving 100% donor myeloid chimerism through 100 days follow-up, the third sickle cell disease participant achieving 100% donor myeloid chimerism through 30 days follow-up, and all three participants increasing their hemoglobin … levels at last follow-up,” Martell said in an emailed statement to Sickle Cell Disease News.

In addition to its potential role as a conditioning agent, briquilimab is being investigated for other chronic diseases related to stem cells, as well as mast cells — immune cells that also carry CD117.

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