Sangamo Preparing to Launch UK Clinical Trial Testing TX200 Cell Therapy in End-stage Renal Disease

Sangamo Preparing to Launch UK Clinical Trial Testing TX200 Cell Therapy in End-stage Renal Disease

Sangamo Therapeutics is preparing to launch a Phase 1/2 clinical study in the United Kingdom to explore the potential of its cell-based CAR-Treg therapyTX200 — in preventing immune-mediated rejection of transplanted kidneys in patients with end-stage renal disease.

The U.K.’s Medicines Healthcare Products Regulatory Agency has approved the proposed protocol for TX200’s first-in-human clinical trial, which is expected to start recruiting participants in 2020.

People with atypical hemolytic uremic syndrome (aHUS) can experience kidney damage and are at risk for advanced chronic kidney disease and renal failure. Thus, many patients need to undergo blood transfusions, dialysis, and in some cases, kidney transplant.

The open-label trial, which will be called STEADFAST, is expected to be conducted in five countries in Europe, namely the U.K., France, the Netherlands, Germany, and Belgium.

Researchers will assess the safety and efficacy of ascending doses of TX200 to prevent graft rejection after a kidney transplant. Collected clinical data also will be used to identify the optimal dosage of the cell therapy, which will be used for further clinical testing in future human trials.

“Being the first company to test a CAR-Treg candidate in humans is an important milestone for Sangamo and this exciting new frontier of cellular therapy,” Adrian Woolfson, BM, BCh, PhD, head of research and development at Sangamo, said in a press release. “We believe that the TX200 program will be invaluable in expanding our understanding of the safety and mechanism of action of CAR-Treg cells and their relevance in the clinic.”

TX200 consists of a subset of immune cells — called T regulatory cells or Tregs — that are collected from the patient and modified in the lab to specifically recognize and target the HLA-A2 protein. This protein belongs to the human leukocyte antigen (HLA) system, which is the primary mechanism that contributes to donor-recipient organ transplant incompatibility.

If the HLA system of both donor and recipient are not compatible, it can result in immune-mediated rejection of the transplanted organ, often also called graft-versus-host disease.

Sangamo’s HLA-A2 CAR-Treg cells are designed to accumulate within the transplanted kidney where the HLA‑A2 protein is present. The modified Tregs are believed to be able to suppress any immune responses that could cause damage to the new kidney. They also are thought to induce immune tolerance, potentially resulting in no need for additional immune-suppressive therapies.

“This innovative and personalized cellular therapy approach for HLA-A2 mismatched kidney transplantation is designed to help regulate the body’s immune system specifically and locally to promote acceptance of an immunologically mismatched donor organ,” Woolfson said. “Beyond transplantation, we plan to explore the potential of CAR-Tregs in a range of autoimmune and inflammatory diseases.”

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Margarida graduated with a BS in Health Sciences from the University of Lisbon and a MSc in Biotechnology from Instituto Superior Técnico (IST-UL). She worked as a molecular biologist research associate at a Cambridge UK-based biotech company that discovers and develops therapeutic, fully human monoclonal antibodies.