Sangamo Therapeutics, Inc. announced dosing of the first patient in the Phase 1/2 STEADFAST clinical study evaluating TX200, a wholly-owned autologous Chimeric Antigen Receptor Regulatory T Cell (CAR-Treg) cell therapy product candidate for the prevention of immune-mediated rejection in HLA-A2 mismatched kidney transplantation from a living donor. Kidney transplantation is the treatment of choice for patients with end-stage renal disease (ESRD) who must otherwise remain on long-term dialysis. Approximately 21-26% of transplanted kidneys are estimated to be HLA-A2 mismatched.

To prevent graft rejection, transplanted patients are treated with lifelong immunosuppressive therapy, which impacts the body's immune system and is associated with multiple side effects, including an increased risk of severe life-threatening infections, malignancies, cardiovascular disease, and other drug-related toxicities, such as nephrotoxicity, which can impact the function and survival of the newly transplanted kidney. TX200 was designed with the potential to prevent kidney rejection by reducing local inflammation and promoting immunological tolerance to the graft. TX200 is composed of autologous Treg cells engineered to express an HLA-A2 CAR.

This investigational cell therapy is being assessed in HLA-A2 negative patients receiving a mismatched HLA-A2 positive kidney from a living donor. TX200 cells are expected to localize to the graft and activate upon binding to the HLA-A2 antigen. Through their ability to regulate the immune system, TX200 cells may protect the graft from immune-mediated rejection and reduce or eliminate the need for lifelong treatment with immunosuppressants.

In the STEADFAST clinical study, each patient undergoes a leukapheresis procedure to collect their white blood cells, after which their Treg cells are isolated, genetically engineered and then cryopreserved. The patient subsequently undergoes transplantation surgery to receive a kidney from a living donor. Following a recovery period, the patient receives their personalized TX200 investigational cell therapy.

Dosing of patients therefore occurs several months after patient enrollment. Sangamo expects to dose a second patient in the STEADFAST study in the middle of 2022. The STEADFAST study forms the first step in a pipeline of CAR-Treg programs. In addition to TX200, Sangamo is developing CAR-Treg cell therapy candidates in preclinical studies, including for potential use in treating multiple sclerosis and inflammatory bowel disorders.