New Collaboration to Evaluate Lower-Dose Gene Therapy Conditioning for Sickle Cell Disease


Jasper Therapeutics and Aruvant Sciences are studying the use of JSP191 used with ARU-1801 in patients with sickle cell disease.

Jasper Therapeutics and Aruvant Sciences are collaborating to study the use of JSP191, an antibody-based conditioning agent, with ARU-1801, an investigational lentiviral gene therapy for the treatment of sickle cell disease (SCD).1

The goal of the collaboration is to evaluate the use of JSP191, a highly targeted anti-CD117 monoclonal antibody, as an effective and more tolerable conditioning agent that can expand the number of patients who can receive ARU-1801.

"This research collaboration with Aruvant is the first to use a clinical-stage antibody-based conditioning agent and a novel clinical-stage gene therapy, giving this combination a clear advantage by moving beyond the harsh conditioning agents currently used for gene therapy and establishing this next-generation potentially curative treatment as a leader in sickle cell disease," said Kevin N. Heller, MD, executive vice president, research and development, Jasper, in a statement. "Our goal is to establish JSP191 as a potential new standard of care conditioning agent, broadly in autologous gene therapy and allogeneic hematopoietic stem cell transplantation."

Gene therapy conditioning, used to help facilitate the engrafting of new, gene-modified stem cells, typically involves the use of high-dose chemotherapy such as busulfan, whose adverse events (AEs) may include infection, bleeding, secondary malignancy, and infertility. 

The AEs associated with gene therapy conditioning and the limited efficacy shown so far with low-dose conditioning has limited the use of hematopoietic cell transplantation despite its potential as a treatment for serious diseases. 

The Lentiviral ARU-1801

ARU-1801 has demonstrated durable efficacy with a lower dose of chemotherapy and a different agent with less associated AEs. The gene therapy addresses the limitations of current curative treatment options, such as low donor availability and the risk of graft-versus-host disease seen with allogeneic stem cell transplants, and unlike other approaches, requires only reduced intensity conditioning as opposed to fully myeloablative conditioning.

The ongoing phase ½ MOMENTUM study (NCT02186418) in patients with severe SCD,has demonstrated durable reductions in disease burden. The study has enrolled 10 participants and is estimated to meet primary completion in 2023, although follow-up will continue for another 13 years. Primary outcomes include incidence of grade 3 allergic reaction, grade 4 infection, grade 4 neutropenia, and grade 3 or 4 organ toxicity.2

JSP191 Conditioning Therapy

JSP191 is designed to block stem cell factor receptor signaling leading, which will clear hematopoietic stem cells from bone marrow and allow new stem cells to engraft. It is in clinical development and has been evaluated in more than 90 healthy volunteers and patients. It is currently being evaluated in 2 clinical trials for myelodysplastic syndromes (MDS)/acute myeloid leukemia (AML) and severe combined immunodeficiency (SCID). 

Jasper Therapeutics announced positive data from the phase 1 trial of JSP191 in patients with MDS/AML (NCT04429191) in February. The first 6 patients to receive a single dose of JSP191 prior to transplantation showed successful engraftment and complete donor myeloid chimerism (at least 95%) was observed in 5 patients at 28 days, and all 3 evaluated patients had total donor chimerism of at least 95% at day 90. Three of 5 evaluated patients showed complete eradication of measurable residual disease (MRD) as measured by next-generation sequencing at 28 days. Two of 5 evaluable patients showed substantial reductions in MRD. No treatment-related serious AEs were reported.3

Four additional studies are expected to begin enrollment in 2021 for patients with severe autoimmune disease, SCD, chronic granulomatous disease, and Fanconi anemia undergoing hematopoietic cell transplantation.

"The unique attributes of ARU-1801 enable us to bring a potentially curative one-time therapy to individuals with sickle cell disease that can be delivered in the safest way possible," Will Chou, MD, chief executive officer, Aruvant, added to the statement. "By partnering with Jasper to evaluate the use of JSP191 with ARU-1801, we are one step closer to developing a next-generation definitive therapy with an even more patient-friendly conditioning regimen. We believe that this combination may be able to further expand the number of patients who can benefit from ARU-1801 in the future, including potentially those with more moderate disease."

1. Jasper Therapeutics and Aruvant announce research collaboration to study JSP191, an antibody-based conditioning agent, with ARU-1801, a novel gene therapy for the treatment of sickle cell disease. News release. Jasper Therapeutics. June 21, 2021.
2. Gene transfer for patients with sickle cell disease (NCT02186418). NIH US National Library of Medicine.
3. Jasper Therapeutics announces positive data from phase 1 clinical trial of JSP191 as targeted stem cell conditioning agent in patients with myelodysplastic syndromes or acute myeloid leukemia undergoing hematopoietic cell transplantation. News release. Jasper Therapeutics. February 8, 2021.
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