FDA Approves Orca Bio’s TREGZI to Improve Chronic GVHD-Free Survival After Allogeneic Stem Cell Transplant in Adults with Hematologic Malignancies

The U.S. Food and Drug Administration (FDA) has approved TREGZI™ (allogeneic regulatory T cell immunotherapy with HSPC and T cells-vldq) for adults with hematologic malignancies undergoing matched-donor allogeneic hematopoietic stem cell transplantation (alloHSCT) following a myeloablative preparative regimen. The therapy is indicated for hematopoietic and immunologic reconstitution and to improve chronic graft-versus-host disease (GVHD)-free survival.

The approval marks the first FDA authorization of a highly purified regulatory T cell (Treg)-based therapy and introduces a precision-engineered cell therapy that addresses one of the major limitations of allogeneic transplantation: reducing GVHD without compromising the graft-versus-leukemia effect.

Precision-engineered cell therapy targets immune reconstitution while limiting GVHD

TREGZI is an individualized cell therapy manufactured from a matched donor for each patient. The product combines hematopoietic stem and progenitor cells (HSPCs), highly purified regulatory T cells (Tregs), and conventional T cells (Tcons). HSPCs restore hematopoiesis, Tregs suppress harmful immune responses responsible for GVHD, while Tcons promote immune recovery and preserve graft-versus-leukemia activity.

The therapy is intended for adults with blood cancers including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), high-risk myelodysplastic syndrome (MDS), and mixed-phenotype acute leukemia (MPAL), diseases in which allogeneic transplantation remains a potentially curative option but carries substantial risks of chronic GVHD, infections, and treatment-related mortality.

Phase 3 Precision-T trial showed significant improvements across key transplant outcomes

FDA approval was supported by the randomized, open–label, multicenter Precision-T Phase 3 trial (NCT05316701), which enrolled 187 patients across 19 U.S. transplant centers. The study compared TREGZI plus single-agent tacrolimus with conventional alloHSCT plus tacrolimus and methotrexate. Results were published in Blood in December 2025.

At 12 months, TREGZI achieved the primary endpoint of chronic GVHD-free survival in 78% of patients compared with 38% receiving conventional alloHSCT (HR 0.26; p<0.00001). The benefit was driven by substantially lower rates of chronic GVHD and reduced mortality.

Additional efficacy findings included:

• Chronic GVHD occurred in 13% of TREGZI-treated patients versus 44% with conventional transplantation (HR 0.19; p<0.00002).
• Overall survival reached 94% compared with 83% in the control arm.
• GVHD-free and relapse-free survival (GRFS) improved to 63% versus 31%.
• Non-relapse mortality decreased to 3%, compared with 13% following standard alloHSCT.

Safety findings remained consistent with previous studies. Grade 3 or 4 acute GVHD by day 180 occurred in 6% of patients receiving TREGZI compared with 10% in the control group (HR 0.37; p=0.044). Grade 3 or higher infections were also less frequent, with estimated one-year incidences of 44% and 51%, respectively.

Experts highlight a new approach to reducing transplant toxicity

Robert Negrin, M.D., Professor of Medicine in Blood and Marrow Transplantation at Stanford Medicine, said the FDA approval represents the culmination of decades of research into regulatory T-cell biology, marking the first approved therapy to use highly purified regulatory T cells. He noted that the Phase 3 findings demonstrated improved GVHD-free survival with lower toxicity, including fewer serious infections and reduced non-relapse mortality.

Nate Fernhoff, Ph.D., co-founder and Chief Executive Officer of Orca Bio, said the company will now focus on the commercial rollout of TREGZI, prioritizing reliable manufacturing, precision delivery, and safe access for eligible patients undergoing matched-donor stem cell transplantation.

Miguel-Angel Perales, M.D., Chief of the Adult Bone Marrow Transplant Service at Memorial Sloan Kettering Cancer Center, said the approval marks a new era in transplant medicine by providing physicians with a precision-engineered therapy that reduces serious transplant-related toxicities while preserving anti-leukemia activity.

Together, the approval establishes Orca Bio’s first commercial product and advances precision-engineered immune cell therapies as a new approach to improving outcomes after allogeneic stem cell transplantation.

Reference

Orca Bio’s TREGZI™ Receives U.S. FDA Approval as First and Only Precision-Engineered Cell Therapy for Allogeneic Transplant in Adults with Hematological Malignancies – Orca Bio