Tregzi (allogeneic regulatory T cell immunotherapy with HSPC and T cells-vldq) / Orca Biosystems - LARVOL DELTA

Allogeneic HSC and regulatory T cell (Orca-T) engineered cell therapy following reduced intensity conditioning: Results of a single center Phase 1 study (ASH 2025) - P3 | "Fourteen subsequent patients received 10mg/kg of thiotepa instead of melphalan,with the same dosing of fludarabine and 4 Gy TBI. These early results demonstrate that Orca-T is a safe and feasible transplant strategy forRIC conditioning. The trial achieved the goal of identifying a lympho-depletive RIC conditioning regimentolerated in the outpatient setting. Patients showed robust engraftment and donor T cell chimerism."

Clinical • P1 data • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Hepatology • Immunology • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm

SOHO State of the Art Updates and Next Questions | Best of Stem Cell Transplant: Recent Advances in Allogeneic Hematopoietic Cell Transplantation. (PubMed, Clin Lymphoma Myeloma Leuk) - "The adoption of post-transplant cyclophosphamide (PTCy) as a near-universal GVHD prophylaxis backbone has diminished the long-standing primacy of human leukocyte antigen matching, enabling comparable outcomes with mismatched unrelated (MMUD) and haploidentical donors and expanding access for patients of non-European ancestry; contemporary guidelines now endorse concurrent donor searches and prioritization of younger donors...Complementary strategies, including frontline and prophylactic ruxolitinib, adoptive regulatory T-cell (Treg) therapy, and the precision-engineered Orca-T graft, are broadening the prophylaxis repertoire and beginning to separate GVHD control from the loss of immune competence and graft-versus-leukemia activity. For FLT3-ITD AML, the MORPHO trial and subsequent analyses have established measurable residual disease-directed gilteritinib maintenance, advancing a molecularly individualized approach to relapse prevention. Together, these developments..."

Journal • Review • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Oncology • Transplantation • FLT3

OBSERVATIONAL COMPARISON OF OVERALL SURVIVAL BETWEEN PHASE 1B ORCA-T® AND REGISTRY-BASED POST-TRANSPLANT CYCLOPHOSPHAMIDE PATIENTS (EBMT 2025) - P1 | "Additionally, MAC regimens for the Ph1b' cohort were limited to busulfan/fludarabine/thiotepa, or total body irradiation (TBI)/cyclophosphamide, or TBI/etoposide between 2019-2024. Comparison of Orca-T phase 1b and PTCy patients from the CIBMTR registry demonstrated higher OS for Orca-T patients. The study was limited to OS and retrospective data, and further analysis is needed to explore factors like infection, relapse, and organ toxicity. A phase 3 randomized trial comparing Orca-T with single agent tacrolimus to conventional transplant with tacrolimus/methotrexate GvHD prophylaxis has recently completed accrual."

Clinical • P1 data • Post-transplantation • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation

SERENE-T: A Phase 2 Trial of Orca-T Following Reduced-Intensity or Nonmyeloablative Conditioning in Patients With Acute Myeloid Leukemia or Myelodysplastic Syndromes (SOHO 2026) - P2 | "Participants in the RIC cohort will receive TBI 200 or 400 cGy, thiotepa 5 mg/kg, and fludarabine 160 mg/m2 conditioning. Participants in the NMA cohort will receive fludarabine 120 mg/m2 or 150 mg/m2 cyclophosphamide 50 mg/kg, and TBI 200-cGy conditioning... The SERENE-T study is currently enrolling participants across multiple sites in the United States, with an anticipated total enrollment of 80 participants. The trial is designed to further characterize the safety and tolerability of Orca-T and to evaluate the preliminary efficacy of Orca-T in participants eligible for RIC-alloHSCT or NMA-alloHSCT. aGVHD: acute GVHD, AML: acute myeloid leukemia, cGFS: chronic GVHD-free survival, cGVHD: chronic GVHD, CR/CRi: complete remission/complete remission with incomplete hematologic recovery, GRFS: GVHD-free and relapse-free survival, GVHD: graft-vs-host disease, HLA: human leukocyte antigen, MDS: myelodysplastic syndromes, NRM: nonrelapse mortality, OS: overall survival,..."

Clinical • P2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Orca Bio Announces the Publication of TREGZI Long-Term Overall Survival Data in Transplantation and Cellular Therapy (Yahoo Finance) - "'Allogeneic stem cell transplant has long been considered the only curative option for advanced hematologic malignancies, but the risks associated with them – including graft versus host disease (GVHD) - are potentially life threatening,' said Caspian Oliai, MD...'While there are treatment options available to help prevent GVHD, data on the impact of them on overall survival have been limited. The findings from this retrospective analysis on the recently approved therapy, TREGZI, point to the value of cell therapy in potentially improving transplant outcomes for patients without sacrificing long-term survival.'"

Media quote

Orca-T, A Precision Engineered Allograft, Results in High GVHD-Free and Relapse-Free Survival Following Myeloablative Conditioning for Hematological Malignancies (SOHO 2022) - "Patients received MAC (busulfan-based, n=109; TBI-based, n=27; BCNU, n=2) followed by GVHD prophylaxis with either single-agent tacrolimus (n=127), sirolimus (n=7), or tacrolimus plus mycophenolate (n=4, MMUD). A contemporaneous CIBMTR-based control arm was obtained that consisted of patients with similar diagnoses who received MAalloHSCT from a PB source followed by tacrolimus/methotrexate prophylaxis... Results from patients treated with Orca-T, a highprecision Treg-engineered donor product, suggest a reduction in cGVHD, improved GRFS, and low toxicity relative to historic data. A multicenter randomized-control phase 3 trial comparing Orca-T to SOC is enrolling."

Acute Myelogenous Leukemia • Chronic Myeloid Leukemia • Hematological Malignancies • Oncology • CSF3

Orca-T: First Approval. (PubMed, Mol Diagn Ther) - "On 30 June 2026, Orca-T received its first approval in the USA for use in matched donor haematopoietic stem cell transplantation (HSCT) with myeloablative preparative regimen, for haematopoietic and immunologic reconstitution and to improve cGVHD-free survival, in the treatment of adults with haematological malignancies. This article summarizes the milestones in the development of Orca-T leading to this first approval for the prevention of cGVHD."

Journal • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Oncology • Transplantation

ORCA-T® DEMONSTRATES IMPROVED SURVIVAL FREE OF CHRONIC GVHD COMPARED TO CONVENTIONAL ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANT: A RANDOMIZED PHASE 3 TRIAL IN ADVANCED HEMATOLOGIC MALIGNANCIES (EBMT 2025) - P3 | "We report results from the randomized, phase 3 component of Precision-T study comparing Orca-T to a conventional allograft with Tacrolimus/Methotrexate (Tac/MTX) (NCT05316701). The randomized phase 3 trial met its primary endpoint, demonstrating higher cGFS with Orca-T compared to Tac/MTX, owing to significantly reduced chronic GVHD and a positive trend in OS. Results suggest Orca-T may be considered as a new standard of care for patients with hematologic malignancies and HLA-matched donors following myeloablative conditioning. Clinical Trial Registry: NCT05316701https://clinicaltrials.gov/study/NCT05316701"

Clinical • Metastases • P3 data • Acute Graft versus Host Disease • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation

Orca-T versus allogeneic hematopoietic stem cell transplantation (PRECISION-T): a multicenter, randomized phase 3 trial. (PubMed, Blood) - P3 | "To prevent graft-versus-host disease (GVHD) in patients undergoing myeloablative allogeneic hematopoietic stem cell transplantation (alloHSCT), a calcineurin inhibitor plus methotrexate is routinely used. Additionally, significantly less toxicity was observed with Orca-T patients including fewer serious infectious complications and less non-relapse mortality. (ClinicalTrials.gov number NCT05316701)."

Journal • P3 data • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation

Mature Outcomes from the Phase I Trial of Orca-T and Allogeneic CD19/CD22 CAR-T cells for Adults with High-Risk B-ALL (TCT-ASTCT-CIBMTR 2026) - P1 | "Here, we report final safety and anti-tumor activity of the combination of allogeneic anti- CD19/CD22 CAR T cells with a myeloablative graft-engineered HCT in pts with HR B-ALL. This paradigm- shifting combination of CAR T and HCT resulted in 100% DFS without graft failure, significant GVHD, or severe CAR-mediated toxicity. We hypothesize this is due to tolerance for CAR molecules, resulting in persistent CAR expression and improved antitumor activity."

CAR T-Cell Therapy • Clinical • IO biomarker • P1 data • Acute Graft versus Host Disease • B Acute Lymphoblastic Leukemia • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology • Infectious Disease • CD22

Clinical Overview of Infection Events With Orca-T vs Conventional Allogeneic Hematopoietic Stem Cell Transplantation in the Precision-T Phase 3 Study (SOHO 2026) - P3 | "Introduction: Allo-HSCT can be curative for high-risk hematologic malignancies; however, infections remain a frequent and severe complication. Severe infections with Orca-T were manageable and fewer than with TAC/MTX. Prior work using T cell–depleted allografts identified a prognostic threshold of 50 CD4 T cells/μL by D100 to define functional immune reconstitution; Orca-T demonstrated median immune reconstitution above that by D28. Although the TAC/MTX arm had a greater number of T cells in the months post allo-HSCT, Orca-T participants demonstrated a potential decrease in severe infection risk."

Clinical • P3 data • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • CD4

Observational Comparison of Overall Survival between Phase 1b Orca-T and Registry-Based Post-Transplant Cyclophosphamide Patients. (PubMed, Transplant Cell Ther) - "Within the limitations of this retrospective analysis, these results suggest that survival following alloHSCT may be improved with Orca-T relative to PTCy."

Clinical • Journal • P1 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Oncology • Transplantation

Myeloablative Conditioning Orca-T & Allogeneic Donor-Derived CD19/CD22-CAR TCells in B-Cell ALL (clinicaltrials.gov) - P1 | N=22 | Active, not recruiting | Sponsor: Stanford University | Trial completion date: May 2026 ➔ Dec 2045

Trial completion date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • CD19 • CRLF2 • HLA-B • HLA-C • HLA-DRB1 • KMT2A

FDA approves cell therapy to reduce GVHD risk after transplant (Rare Cancer News) - "'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,' Miguel-Angel Perales, MD...said in a press release from Orca Bio. '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.'"

Media quote • Regulatory

Orca Bio's TREGZI Receives US FDA Approval as First and Only Precision-Engineered Cell Therapy for Allogeneic Transplant in 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, MD...'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.'"

Media quote • Regulatory

Trial for Patients w/ Advanced Hematologic Malignancies Undergoing Allogeneic HCT (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Stanford University | Trial primary completion date: May 2026 ➔ Dec 2026

Trial primary completion date • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • HLA-B • HLA-C • HLA-DRB1

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 (Businesswire) - "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)."

FDA approval • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Chronic Graft versus Host Disease • Myelodysplastic Syndrome

Orca Bio…announced key manufacturing updates ahead of the anticipated commercial launch of its lead investigational cell therapy, Orca-T, including new East Coast manufacturing capacity in Princeton, NJ, and significant expansion of its existing manufacturing team in Sacramento, CA (Businesswire) - "The Princeton site will initially produce therapies for patients in Orca Bio's ongoing clinical programs, and is expected to support commercial production following the potential FDA approval of Orca-T and validation of its manufacturing lines....The Biologics License Application (BLA) for Orca-T is currently under review with the FDA with a Prescription Drug User Fee Act (PDUFA) target action date of July 6, 2026."

Commercial • PDUFA • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Myelodysplastic Syndrome

Orca Bio…announced that the U.S. Food and Drug Administration (FDA) has extended the review timeline of its Biologics License Application (BLA) for Orca-T for the treatment of patients with hematologic malignancies. (Businesswire) - "The new Prescription Drug User Fee Act (PDUFA) target action date is July 6, 2026. The extension follows Orca Bio's recent submission of updated chemistry, manufacturing and controls (CMC) information in response to requests from the FDA as part of the standard review process. The FDA classified the submission as a Major Amendment (MA) to the BLA, which extends the review by three months."

PDUFA • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Myelodysplastic Syndrome

Harnessing Regulatory T Cell (Treg) Biology: Cutting-Edge Immunotherapies for Cancer, Autoimmunity, and Transplantation (FOCIS 2026) - "He'll highlight results from the groundbreaking phase II and III Orca-T trials, along with promising new approaches using CAR-Tregs to induce long-term immune tolerance in transplant recipients...Megan Levings will spotlight innovative strategies for autoimmune diseases, including next-generation cell therapies such as "armored" CAR Tregs engineered with a PD-1 promoter-driven IL-10 payload to boost suppressive function. Together, these talks offer a glimpse into the future of immunotherapy—where precision-engineered Tregs may hold the key to curing disease and restoring immune balance."

Graft versus Host Disease • Immunology • Transplant Rejection • CD8 • IL10 • IL33 • PD-1

Phase 1 Precision-T: Precision-T: A Study of Orca-T in Recipients Undergoing Allogeneic Transplantation for Hematologic Malignancies (clinicaltrials.gov) - P1 | N=155 | Active, not recruiting | Sponsor: Orca Biosystems, Inc. | N=255 ➔ 155

Enrollment change • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation

Orca-T as a force multiplier for HCT immune tolerance. (PubMed, Blood) - No abstract available

Journal

Orca-T Following Chemotherapy and Total Marrow and Lymphoid Irradiation for the Treatment of Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia or Myelodysplastic Syndrome (clinicaltrials.gov) - P1 | N=33 | Recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Jun 2027 ➔ Mar 2030 | Trial primary completion date: Jun 2027 ➔ Mar 2030

Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • FLT3

Clinical and translational advances in regulatory T cell-based strategies in allogeneic hematopoietic stem cell transplantation: highlights from ASH 2025. (PubMed, Exp Hematol Oncol) - "Accordingly, Tregs are used as GVHD prophylaxis via the Orca-T platform and as a therapeutic strategy for steroid-refractory (SR)-GVHD patients. Experimental studies further pave the way to address existing limitations toward next-generation Treg-based cell therapy in allo-HSCT."

Journal • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Oncology • Transplantation

SCALABLE MANUFACTURING AND NATIONWIDE DISTRIBUTION OF ORCA-T: A PRECISION-ENGINEERED ALLOGENEIC IMMUNE CELL THERAPY (EBMT 2026) - P1, P3 | "Collectively, these findings establish the feasibility of precision-engineered cell therapy manufacturing and distribution to enable multicenter clinical studies and lay the foundation for future commercial application.Figure 1: Apheresis Centers and Transplant Centers participating in the Phase 1b (NCT4013685) and Phase 3 (NCT05316701) trials of Orca-T"

Immune cell