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iStock, slowmotiongli The approval of Tregzi—the first regulatory greenlight for Orca Bio—was based on a Phase 3 study in which patients on the therapy were twice as likely to survive without cancer relapse and without chronic GVHD compared with conventional allogeneic transplant. The FDA has greenlit Orca Bio’s allogeneic T cell–based immunotherapy to reduce graft-versus-host disease in patients being treated for blood cancers. Tregzi marks the first approval of a cell therapy using regulatory T cells, according to the biotech. Tregzi is also Orca’s first approved therapy, “validating the company’s high-precision platform and the potential of its pipeline,” the California-based company said in a Tuesday press release . “Today’s approval marks a defining moment for Orca Bio and for the future of allogeneic transplant, which has long offered curative potential, but also carries significant risks like graft versus host disease,” Orca CEO and co-founder Nate Fernhoff told BioSpace in a Tuesday statement. Tregzi, which uses hematopoietic stem and progenitor cells (HSPCs) to reconstitute the immune system and highly purified regulatory T cells (Tregs) to suppress GVHD, “was developed to build on the foundation of transplant – applying precision science to improve how it is manufactured and delivered,” Fernhoff added. GVHD is a severe complication that can occur after a stem cell or bone marrow treatment. It arises when donor immune cells attack the recipient’s body, leading to inflammation and tissue damage. “For patients with blood cancers who need stem cell transplantation, chronic graft-versus-host disease has long been one of the most feared and difficult-to-prevent complications,” Karim Mikhail, acting director of the FDA’s Center for Biologics Evaluation and Research, said in a prepared statement on Tuesday. “Today’s approval offers a genuine new approach that can help reconstitute the immune system while substantially reducing that risk and reflects the promise of what cellular therapy can deliver for patients.” The FDA nod for Tregzi is based on the results of Orca’s Precision-T Phase 3 study , which tested the therapy in 187 patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), myelodysplastic syndrome (MDS) and mixed-phenotype acute leukemia. The patients were randomly assigned to receive either Tregzi plus single-agent tacrolimus (TAC) or a conventional allogeneic hematopoietic stem cell transplant (alloHSCT) plus TAC/methotrexate. Patients on Orca’s therapy saw “significantly higher rates of chronic GVHD-free survival,” according to the FDA’s release, with 78% of patients achieving this outcome compared to 38.4% of those who underwent a standard transplant. GVHD-free and relapse-free survival was more than double for patients given Tregzi, while overall survival was 94% with Tregzi and 83% with alloHSCT. Tregzi’s safety pro also strong, with side effects “generally consistent with those expected in patients undergoing stem cell transplantation,” according to the FDA. Robert Negrin, professor of medicine, blood and marrow transplantation at Stanford Medicine, in a prepared statement called Tregzi’s approval “a defining moment for the transplant community.”

The approval of TREGZI, clinically known as Orca-T ® , marks a significant milestone for patients as a novel, personalized cell therapy for use in a stem cell transplant to improve survival free of chronic graft versus host disease (GVHD) in adults with hematological malignancies Approval is based on the pivotal Precision-T study which demonstrated patients receiving TREGZI were twice as likely to be alive without chronic GVHD at one year compared with conventional allogeneic transplant TREGZI is Orca Bio’s first approved therapy, validating the company’s high-precision platform and the potential of its pipeline MENLO PARK, Calif.--(BUSINESS WIRE)--Orca Bio, a commercial-stage biotechnology company committed to transforming the lives of patients through high-precision cell therapy, today announced the U.S. Food and Drug Administration (FDA) has approved TREGZI ™ (allogeneic regulatory T cell immunotherapy with HSPC and T cells-vldq), clinically known as Orca-T ® , a precision-engineered cell therapy for use in matched-donor hematopoietic stem cell transplantation with myeloablative preparative regimen, for hematopoietic and immunologic reconstitution and to improve chronic graft-versus-host disease (GVHD)-free survival (cGFS), in the treatment of adults with hematological malignancies. “For transplant physicians, one of our greatest challenges has long been preserving the vital graft-versus-leukemia effect while minimizing the risk of GVHD and infection,” said Miguel-Angel Perales, M.D., medical oncologist and chief of the Adult Bone Marrow Transplant Service at Memorial Sloan Kettering Cancer Center. “The FDA approval of TREGZI signals a new era in transplant medicine. This precision-engineered cell therapy is built on the foundational principles established by our early CD34 cell selection work and can now be delivered at scale, equipping providers with a new option to reduce serious toxicities and improve treatment outcomes.” “We founded Orca Bio on the audacious goal to engineer living cells into curative medicines, rooted in the belief that single-cell precision could fundamentally rewrite patient outcomes,” said Nate Fernhoff, Ph.D., co-founder and chief executive officer of Orca Bio. “The FDA approval of TREGZI is a significant milestone that stands on the shoulders of decades of pioneering science. As we enter this next chapter, our focus turns to the immense responsibility of delivering TREGZI reliably, precisely and safely to the patients and families counting on us.” TREGZI is a personalized treatment manufactured for each individual patient using living cells from a matched donor. TREGZI uses hematopoietic stem and progenitor cells (HSPCs) to reconstitute the immune system, highly purified regulatory T cells (Tregs) to suppress GVHD and conventional T cells (Tcons) to accelerate immune reconstitution and produce graft-versus-leukemia (GVL) activity. “Developing this concept from early foundational research in our labs based upon the fundamental biology of regulatory T cells, to it now receiving the first FDA approval for a therapy that utilizes highly purified Tregs, is a defining moment for the transplant community,” said Robert Negrin, M.D., professor of medicine, blood and marrow transplantation at Stanford Medicine. “The peer-reviewed findings demonstrated this precision-engineered cell therapy delivered improved GVHD-free survival alongside less toxicity, including fewer serious infections and lower non-relapse mortality.” The FDA approval of TREGZI is based on results from the randomized, multi-center Precision-T Phase 3 study of patients (n=187) with a median age of 43.6 years (range 19-65 years) with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), myelodysplastic syndrome (MDS) and mixed-phenotype acute leukemia (MPAL). Results with TREGZI plus single-agent tacrolimus (TAC) compared with a conventional allogeneic hematopoietic stem cell transplant (alloHSCT) plus TAC/methotrexate (TAC/MTX) found the following at 12 months: The primary endpoint of chronic cGFS was 78% with TREGZI compared to 38% with alloHSCT (HR 0.26; p<0.00001), an improvement driven by a reduction in chronic GVHD and fewer patient deaths. The rate of chronic GVHD was 13% and 44% with TREGZI and alloHSCT, respectively (HR 0.19; p<0.00002). Overall survival (OS) was 94% with TREGZI and 83% with alloHSCT. GVHD-free and relapse-free survival (GRFS) was 63% and 31% with TREGZI and alloHSCT, respectively. Non-relapse mortality (NRM) was 3% for TREGZI compared with 13% for alloHSCT. Additional safety findings were consistent with previous studies. The cumulative incidence for Grade 3 or 4 acute GVHD at day +180 with TREGZI was 6% versus 10% with alloHSCT (HR 0.37; p=0.044). Grade ≥3 infections were less common with TREGZI, with a one year estimated incidence of 44% for TREGZI and 51% for alloHSCT. “Historically, surviving a blood cancer has often meant navigating serious, long-term effects that can shape patients’ lives well beyond treatment,” said Gwen Nichols, M.D., executive vice president and chief medical officer at Blood Cancer United. “As a researcher, physician and a patient advocate, it’s exciting that patients will have a new option that may change what life after transplant can look like, including the potential to support recovery and quality of life.” Hematological malignancies such as AML, ALL and MDS, commonly referred to as blood cancers, are cancers that can originate in the bone marrow and disrupt normal cell production. Despite therapeutic advances, these diseases, particularly in adult and high-risk populations, remain associated with poor outcomes, high relapse rates and significant treatment-related toxicities. IMPORTANT SAFETY INFORMATION AND INDICATION WARNINGS AND PRECAUTIONS Graft Failure: Graft failure has occurred after TREGZI administration. Screen TREGZI recipients for antidonor antibodies that may prevent engraftment. Monitor patients closely for laboratory evidence of hematopoietic recovery. Graft-Versus-Host Disease: Acute and chronic Graft-Versus-Host disease (GVHD), including life-threatening and fatal cases, occurred following treatment with TREGZI. Acute GVHD manifests as maculopapular rash, gastrointestinal symptoms, and elevated bilirubin. Chronic GVHD may include skin rash, mouth sores, dry eyes, liver inflammation, and development of scar tissue in the skin and joints and damage to the lungs. Treat patients with a single agent calcineurin inhibitor as prophylaxis to decrease the risk of GVHD. Monitor for signs and symptoms of GVHD, and treat if GVHD develops. Infusion Reactions: Infusion reactions (IRs) may occur during or following treatment with TREGZI. Serious hypersensitivity reactions including anaphylaxis may occur to DMSO, human serum albumin (HSA), Dextran or murine protein present in TREGZI. IRs may begin within minutes of the start of TREGZI infusion, although symptoms may continue to intensify and not peak for several hours after the completion of the infusion. Monitor patients for signs and symptoms of IRs during and after TREGZI administration. When a reaction occurs, pause the infusion and institute supportive care as needed. Premedicate patients with antipyretics and histamine antagonists prior to infusion to reduce the incidence and intensity of infusion reactions. Secondary Malignancies and Malignancies of Donor Origin: Secondary malignancies and malignancies of donor origin may occur following treatment with TREGZI. Development of secondary malignancies, including posttransplantation lymphoproliferative disorder (PTLD) may occur many years after transplantation. PTLD manifests as a lymphoma-like disease favoring non-nodal sites. PTLD is usually fatal if not treated. Serial monitoring of blood for EBV DNA may be warranted in patients with persistent cytopenias. No patient treated with TREGZI has developed PTLD. Monitor for malignancies of donor origin and secondary malignancies. Contact Orca Bio at 1-877-411-6722 if any patient is diagnosed with a secondary malignancy or a malignancy of donor origin. Transmission of Infectious Agents: Transmission of serious infectious or communicable disease or agents may occur with TREGZI treatment as it is derived from human donor blood and manufactured using animal-derived reagents. Risks of transmission of infectious agents may occur despite screening or testing of donors. Risks of transmission of serious infections include, but are not limited to, human immunodeficiency virus, human T cell lymphotropic virus (HTLV)-1 and -2, hepatitis B virus (HBV), hepatitis C virus (HCV), Treponema pallidum, Trypanosoma cruzi, West Nile virus (WNV), cytomegalovirus, transmissible spongiform encephalopathy agents and vaccinia. Monitor patients for signs and symptoms of infections, perform tests for infectious agents and treat as clinically indicated. ADVERSE REACTIONS The most common adverse reactions (incidence ≥ 20%) were mucositis, diarrhea, rash, viral infections, infections pathogen unspecified, abdominal pain, vomiting, nausea, bacterial infections, hemorrhage, aGVHD, edema, and fungal infections. The most common Grade 3-4 laboratory abnormalities (≥ 20%) are lymphocyte count decreased, platelet count decreased, leukocyte count decreased, neutrophil count decreased and hemoglobin decreased. INDICATIONS AND USAGE TREGZI is indicated for use in matched donor hematopoietic stem cell transplantation with myeloablative preparative regimen, for hematopoietic and immunologic reconstitution and to improve chronic graft-versus-host-free survival, in the treatment of adults with hematological malignancies. Please see accompanying full Prescribing Information . About Precision-T Precision-T (NCT05316701) is a randomized, open-label, multi-center study that evaluated the safety, efficacy and tolerability of TREGZI compared with conventional allogeneic hematopoietic stem cell transplant (alloHSCT). Orca Bio received guidance from the U.S. Food and Drug Administration on the design of Precision-T, which evaluated TREGZI in patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), high-risk myelodysplastic syndrome (MDS) and mixed-phenotype acute leukemia (MPAL). There were 19 leading treatment centers participating in the trial, which enrolled 187 patients across the U.S. Results were published in Blood in December 2025 . About Orca Bio Orca Bio is a commercial-stage biotechnology company developing high-precision cell therapies for the treatment of blood cancer and autoimmune diseases. The company’s manufacturing platform uses single-cell precision to create proprietary, uniquely defined products designed to replace a patient’s diseased blood and immune system with a healthy one. Orca Bio is a privately held company that completed Series F financing led by Lightspeed Venture Partners earlier this year. At Orca Bio, we are on a mission to redefine what’s possible for patients by transforming the field of curative allogeneic cell therapy. For more information, visit . Trademarks or registered trademarks used in this press release are the property of their respective owners. Dr. Perales has financial interests related to Orca Bio. Contacts Corporate Communications Kelsey Grossman media@orcabio.com Investor Relations Joshua Murray ir@orcabio.com