13 January 2021 - - US-based biotechnology company Jasper Therapeutics, Inc and gene editing company Graphite Bio, Inc have forged a research and clinical collaboration agreement to evaluate JSP191, Jasper's first-in-class anti-CD117 monoclonal antibody, as a targeted, non-toxic conditioning regimen for Graphite Bio's investigational GPH201 gene replacement therapy for severe combined immune deficiency in patients with IL2RG deficiency, known as x-linked SCID (XSCID), the companies said.

XSCID is a severe, inherited disorder of the immune system with symptoms often presenting in early infancy, including persistent infections and failure to thrive. Without treatment, XSCID is typically fatal to patients in the first two years of life.

Graphite Bio is focused on the development of potentially curative therapies for patients suffering from serious diseases, using its targeted gene integration platform to harness the natural cellular process of homology directed repair in order to efficiently repair genetic defects at their source, deliver genetic cargo with precision and engineer new cellular effector functions.

Jasper Therapeutics' JSP191 is a first-in-class humanized monoclonal antibody that depletes hematopoietic stem cells from bone marrow and acts as a conditioning agent in patients prior to receiving a hematopoietic stem cell transplant.

JSP191 is currently being evaluated in multiple trials as a stem cell depleting conditioning agent, including a Phase 1/2 trial to achieve donor stem cell engraftment in SCID patients undergoing hematopoietic cell transplant and a separate Phase 1/2 trial in AML/MDS patients undergoing hematopoietic cell transplant.

Graphite Bio and Jasper will collaborate on research, and potentially a clinical study, evaluating JSP191 as a conditioning agent for GPH201. Each company will retain commercial rights to their respective technologies.

JSP191 (formerly AMG 191) is a first-in-class humanized monoclonal antibody in clinical development as a conditioning agent that clears hematopoietic stem cells from bone marrow.

JSP191 binds to human CD117, a receptor for stem cell factor that is expressed on the surface of hematopoietic stem and progenitor cells. The interaction of SCF and CD117 is required for stem cells to survive.

JSP191 blocks SCF from binding to CD117 and disrupts critical survival signals, causing the stem cells to undergo cell death and creating an empty space in the bone marrow for donor or gene-corrected transplanted stem cells to engraft.

Preclinical studies have shown that JSP191 as a single agent safely depletes normal and diseased hematopoietic stem cells, including in animal models of SCID, myelodysplastic syndromes and sickle cell disease. Treatment with JSP191 creates the space needed for transplanted normal donor or gene-corrected hematopoietic stem cells to successfully engraft in the host bone marrow.

To date, JSP191 has been evaluated in more than 90 healthy volunteers and patients.

JSP191 is currently being evaluated in two separate clinical studies in hematopoietic cell transplant.

The first clinical study is evaluating JSP191 as a sole conditioning agent in a Phase 1/2 dose-escalation and expansion trial to achieve donor stem cell engraftment in patients undergoing hematopoietic cell transplant for severe combined immunodeficiency, which is potentially curable only by this type of treatment.

JSP191 is also being evaluated in combination with another conditioning regimen in a Phase 1 study in patients with MDS or acute myeloid leukemia who are receiving hematopoietic cell transplant. For more information about the design of these clinical trials, visit www.clinicaltrials.gov (NCT02963064 and NCT04429191).

Additional studies are planned to advance JSP191 as a conditioning agent for patients with other rare and ultra-rare monogenic disorders and autoimmune diseases.

GPH201 is a first-in-human investigational hematopoietic stem cell treatment that will be evaluated as a potentially curative therapy for patients suffering from XSCID.

GPH201 is generated using Graphite Bio's precise and efficient targeted gene integration platform technology to directly replace the defective IL2RG gene, maintain normal IL2RG regulation and expression, and ultimately lead to the production of fully functional adaptive immune cells.