non-malignant blood, immune and metabolic disorders


Severe non-malignant blood, immune and metabolic disorders

Allogeneic HSCT (allo-HSCT) is currently used to treat a wide range of severe non-malignant blood, immune and metabolic disorders, all of which involve functional defects or deficiencies of cells derived from HSCs that mature into our functioning blood and immune systems.

Standard allo-HSCT entails transplanting HSCs collected from a healthy donor into these patients, to potentially cure the patient’s defective cells by replacing them with healthy, donor-derived cells. However, many patients who might benefit from allo-HSCT do not receive it because they are unable to find a suitable HLA-matched donor. Higher degrees of HLA mismatch correlate with greater risk of GvHD. As such, there is a significant unmet need for an approach to allo-HSCT that could enable better clinical outcomes regardless of the degree of HLA mismatch between donor and recipient.


The therapeutic principle of allo-HSCT in these cases is to replace the defective or deficient HSCs in a patient’s bone marrow with normal-functioning HSCs from a healthy donor.

A second major limitation of allo-HSCT for non-malignant indications is that it usually entails fully myeloablative conditioning due to concerns that nonmyeloablative conditioning will not promote robust levels and durability of donor chimerism to effectively replace most of the defective HSCs in the recipient’s bone marrow. The intensity and toxicity of myeloablative conditioning regimens is greater than for nonmyeloablative regimens and necessitates a long and costly hospitalization while the recipient’s immune and blood systems reconstitute.

Thus, we believe there is a significant unmet need for a nonmyeloablative approach to allo-HSCT for severe non-malignant blood, immune and metabolic disorders that could enable durable engraftment of healthy donor HSCs with less short- and long-term toxicity and correspondingly shorter hospital stays and lower costs.

Potential for Facilitated Allo-HSCT

In our Phase 2 trial of living donor kidney transplant recipients, FCR001 treatment induced, in a significant portion of patients, high levels (>95%) of durable donor chimerism despite a nonmyeloablative conditioning regimen. We observed evidence of reconstitution of immune and blood cell components (e.g. T-cells, B-cells, natural killer cells, monocytes, granulocytes, and red blood cells) in FCR001 recipients. We also observed a low incidence of acute GvHD and of chronic GvHD in our Phase 2 trial, despite the fact that many of our donor-recipient pairs were significantly HLA-mismatched and unrelated.

We plan to prioritize FCR001 for one or more severe non-malignant blood, immune or metabolic disorders for advancement into IND-enabling studies.