Orca-T / Orca Biosystems - LARVOL DELTA

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

ORCA-T DEMONSTRATES FAVORABLE QUALITY OF LIFE AND HEALTHCARE RESOURCE USE COMPARED TO STANDARD ALLOHSCT PLUS TAC/MTX FOR GVHD PREVENTION IN RANDOMIZED PHASE3 CLINICAL TRIAL (PRECISION-T) (EBMT 2026) - P1 | "Orca-T recipients experienced higher HRQoL, faster recovery, fewer ICU stays, lower rehospitalization rates, and improved rehospitalization-free survival compared to Tac/MTX, suggesting improved early post-transplant recovery and reduced GVHD symptom burden."

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

CLINICAL OUTCOMES IN ORCA-T AND REGISTRY-BASED POST-TRANSPLANT CYCLOPHOSPHAMIDE PATIENTS: AN OBSERVATIONAL COMPARISON (EBMT 2026) - P1, P3 | "In a Phase 3 randomized trial (NCT05316701), in comparison to calcineurin inhibitor/methotrexate prophylaxis, Orca-T met the primary endpoint of improving moderate-to-severe chronic GVHD-free survival (cGFS). In conclusion, Orca-T patients, in comparison to PTCy patients in the CIBMTR registry, exhibited increased OS, increased RFS, and decreased NRM. These observations were consistently observed in stratified analyses, with further separation in clinical effect between Orca-T and PTCy in patients >50 years of age."

Clinical • Clinical data • Post-transplantation • Acute Graft versus Host Disease • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Transplantation

COST-EFFECTIVENESS OF ORCA-T VS ALLO-HCT WITH CONVENTIONAL GVHD PROPHYLAXIS FOR THE TREATMENT OF ADVANCED HEMATOLOGIC MALIGNANCIES IN THE UNITED STATES (EBMT 2026) - P3 | "Orca-T, an investigational, high-precision cell therapy, demonstrated improvement in survival free of moderate-to-severe chronic GVHD compared to conventional allo-HCT with tacrolimus/methotrexate (TAC/MTX) in the pivotal Phase 3 Precision- T trial. Over a patient's lifetime, the model demonstrated that Orca-T can reduce the overall economic burden compared to conventional allo-HCT with TAC/MTX, with the majority of cost savings driven by reductions in aGVHD, infection, and cGVHD management costs. Given the considerable clinical and economic impact of these complications, Orca-T represents a high value therapeutic option for adults with advanced hematologic malignancies, offering both superior clinical outcomes and economic benefits."

Cost effectiveness • HEOR • Metastases • Acute Graft versus Host Disease • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Oncology

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

CLINICAL OUTCOMES IN MYELODYSPLASTIC SYNDROME PATIENTS TREATED WITH ORCA-T OR POST-TRANSPLANT CYCLOPHOSPHAMIDE PATIENTS: A REGISTRY-BASED COMPARISON (EBMT 2026) - P1, P3 | "In a Phase 3 prospectively randomized trial (NCT05316701), Orca-T met the primary endpoint of improving moderate-to-severe chronic GVHD-free survival in comparison to calcineurin inhibitor/methotrexate prophylaxis. In conclusion, MDS patients treated with Orca-T, in comparison to PTCy, exhibited increased OS, increased RFS, decreased relapse, and decreased NRM. These observations provide evidence supporting the use of Orca-T for improved clinical outcomes."

Clinical • Clinical data • Post-transplantation • Acute Graft versus Host Disease • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Immunology • Myelodysplastic Syndrome • Transplantation

INTERIM CLINICAL OUTCOMES IN ORCA-T WITH REDUCED INTENSITY CONDITIONING: AN OBSERVATIONAL COMPARISON TO REGISTRY-BASED POST-TRANSPLANT CYCLOPHOSPHAMIDE PATIENTS (EBMT 2026) - P1, P3 | "In a ph3 randomized trial (NCT05316701), in comparison to calcineurin inhibitor/methotrexate prophylaxis, Orca-T met the primary endpoint of improving moderate-to-severe chronic GVHD-free survival. Interim analyses of RIC + Orca-T patients revealed low GVHD, relapse, and NRM rates. Comparison to RIC + PTCy patients in the CIBMTR registry suggested a clinical benefit of RIC + Orca-T. These findings provide insight for improving clinical outcomes in older patients and high comorbidity patients unable to receive myeloablative conditioning regimens."

Clinical • Clinical data • Post-transplantation • Acute Graft versus Host Disease • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Myelofibrosis • Transplantation

S-MTE Clinical Experiences with Engineered Cell Therapy Orca-T in Allogeneic HCT | Orca Bio (EBMT 2026) - "Sponsored by Orca Bio."

Clinical

Reliable Manufacturing and Nationwide Distribution of Orca-T (Businesswire) - "A manufacturing and distribution analysis from the Phase 3 and Phase 1b Orca-T studies conducted between December 2019 and September 2024 reported on the production of 243 clinical cell therapies, including 215 from single-day and 28 from two-day collections. Overall, 100% of products were delivered to transplant centers across the U.S. within 70 hours, with 99% infused within 72 hours. Product quality was consistent across all three Orca-T components: hematopoietic stem cells, regulatory T-cells and conventional T-cells."

Retrospective data • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Blastic Plasmacytoid Dendritic Cell Neoplasm • Chronic Myeloid Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm

Orca-T Versus PTCy in Patients with Myelodysplastic Syndromes (Businesswire) - "A post-hoc analysis of patients aged 18-65 with MDS compared pooled results from the Phase 3 Precision-T study and the Phase 1b study of Orca-T to a historical cohort from the CIBMTR registry of patients who received a conventional alloHSCT and PTCy in the myeloablative conditioning (MAC) HLA-matched setting. Patients with MDS who were treated with Orca-T (n=25) demonstrated higher one-, two- and three-year OS of 100% compared to the PTCy cohort (n=95) with 80%, 70% and 62%, respectively. At one year, the Orca-T arm showed RFS of 95% versus 64% with PTCy and NRM of 0% versus 9.9%, respectively. Notably, these trends were observed across subgroups including age and donor type."

Retrospective data • Myelodysplastic Syndrome

A new analysis compared outcomes from the single-center, open-label Phase 1 investigator-sponsored trial evaluating Orca-T versus a historical cohort of patients from the CIBMTR registry who received a conventional allogeneic hematopoietic stem cell transplant (alloHSCT) with post-transplant cyclophosphamide (PTCy). (Businesswire) - "Patients receiving Orca-T (n=53) compared with PTCy (n=587) demonstrated improved: Overall survival at one year (OS; 88% vs 72%) and two years (84% vs 61%); Relapse-free survival at one year (RFS; 82% vs 61%) and two years (79% vs 53%); Graft-versus-host-disease relapse-free survival at one year (GRFS; 72% vs 54%) and two years (72% vs 45%); Relapse rates at one and two years (9.7% vs 23%, 9.7% vs 30%) and non-relapse mortality at one and two years (NRM; 8% vs 16%, 12% vs 17%)."

Retrospective data • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm

Phase I Trial for Patients w/ Advanced Hematologic Malignancies Undergoing Allogeneic HCT (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Stanford University | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • HLA-B • HLA-C • HLA-DRB1

Clinical Outcomes in Myelodysplastic Syndrome Patients Treated with Orca-T or Post-Transplant Cyclophosphamide Patients: A Registry-Based Comparison (TCT-ASTCT-CIBMTR 2026) - P1, P3 | "In a Phase 3 prospectively randomized trial (NCT05316701), Orca-T met the primary endpoint of improving moderate-to-severe chronic GVHD-free survival in comparison to calcineurin inhibitor/methotrexate prophylaxis. 3 . Interpret how improved survival and relapse outcomes with Orca-T support its potential to enhance post-transplant efficacy in MDS."

Clinical • Clinical data • Post-transplantation • Acute Graft versus Host Disease • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Immunology • Myelodysplastic Syndrome • Transplantation

Orca-T Demonstrates Favorable Quality of Life and Healthcare Resource Use Compared to Standard Allohsct Plus Tac/MTX for GVHD Prevention in a Randomized phase 3 Clinical Trial (Precision-T) (TCT-ASTCT-CIBMTR 2026) - "Orca-T recipients experienced higher HRQoL, faster recovery, fewer ICU stays, lower rehospitalization rates, and improved rehospitalization-free survival compared to Tac/MTX, suggesting improved early post-transplant recovery and reduced GVHD symptom burden. Describe the randomized Phase 3 study design evaluating Orca-T versus conventional allogeneic hematopoietic stem cell transplantation (alloHSCT) with tacrolimus/methotrexate prophylaxis, including key efficacy and safety outcomes. Assess longitudinal changes in health-related quality of life (HRQoL) and hospitalization metrics as exploratory endpoints reflecting functional recovery and healthcare resource utilization following Orca-T compared with standard alloHSCT."

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

Cost-Effectiveness of Orca-T Vs Allo-HCT with Conventional GVHD Prophylaxis for the Treatment of Advanced Hematologic Malignancies in the United States (TCT-ASTCT-CIBMTR 2026) - "Orca-T, an investigational, high-precision cell therapy, demonstrated improvement in survival free of moderate-to-severe chronic GVHD compared to conventional allo-HCT with tacrolimus/methotrexate (TAC/MTX) in the pivotal Phase 3 Precision- T trial. Over a patient's lifetime, the model demonstrated that Orca-T can reduce the overall economic burden compared to conventional allo-HCT with TAC/MTX, with the majority of cost savings driven by reductions in aGVHD, infection, and cGVHD management costs. Given the considerable clinical and economic impact of these complications, Orca-T represents a high value therapeutic option for adults with advanced hematologic malignancies, offering both superior clinical outcomes and economic benefits. Evaluate the cost-effectiveness of Orca-T compared to conventional allo-HCT with TAC/MTX GVHD prophylaxis using a partitioned survival model."

Cost effectiveness • HEOR • Metastases • Acute Graft versus Host Disease • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Oncology

Clinical Outcomes in Orca-T and Registry-Based Post-Transplant Cyclophosphamide Patients: An Observational Comparison (TCT-ASTCT-CIBMTR 2026) - P1, P3 | "In a Phase 3 randomized trial (NCT05316701), in comparison to calcineurin inhibitor/methotrexate prophylaxis, Orca-T met the primary endpoint of improving moderate-to-severe chronic GVHD-free survival (cGFS). Assess key efficacy outcomes including overall survival, relapse-free survival, and non-relapse mortality across treatment cohorts. Interpret the consistency of improved survival outcomes with Orca-T, particularly among patients older than 50 years, within subgroup analyses."

Clinical • Clinical data • Post-transplantation • Acute Graft versus Host Disease • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Transplantation

Single Center phase 1b Study of Orca-T Following Escalated Doses of Total Marrow and Lymphoid Irradiation (TMLI) in Patients with Acute Leukemia or MDS (TCT-ASTCT-CIBMTR 2026) - P1 | "Previously, we showed TMLI combined with fludarabine/melphalan Flu/Mel conditioning prior to PBSC HCT is safe and promising, however Graft-versus-Host disease GVHD rates remain high when the regimen is combined with CNI-based GVHD prophylaxis Al Malki et al EBMT 2024 . 3 . Enrollment is ongoing for NCT06195891 to determine the RP2D."

Clinical • P1 data • Acute Graft versus Host Disease • Anorexia • Chronic Graft versus Host Disease • Febrile Neutropenia • Graft versus Host Disease • Hematological Malignancies • Hypertension • Immunology • Myelodysplastic Syndrome • Neutropenia

Scalable Manufacturing and Nationwide Distribution of Orca-T: A Precision-Engineered Allogeneic Immune Cell Therapy (TCT-ASTCT-CIBMTR 2026) - P3 | "Evaluate the role of centralized GMP manufacturing and the OrcaPort logistics platform in maintaining product integrity and delivery timelines. Analyze manufacturing and distribution metrics that demonstrate feasibility for multicenter clinical implementation and future commercial scalability."

Immune cell

Interim Clinical Outcomes in Orca-T with Reduced Intensity Conditioning: An Observational Comparison to Registry-Based Post-Transplant Cyclophosphamide Patients (TCT-ASTCT-CIBMTR 2026) - P1, P3 | "In a ph3 randomized trial (NCT05316701), in comparison to calcineurin inhibitor/methotrexate prophylaxis, Orca-T met the primary endpoint of improving moderate- to-severe chronic GVHD-free survival. Assess relapse-free, GVHD- and relapse-free, and chronic GVHD-free survival outcomes comparing RIC + Orca-T versus RIC + PTCy cohorts. Interpret the clinical relevance of low GVHD incidence and improved survival metrics with RIC + Orca-T in older or comorbid transplant candidates."

Clinical • Clinical data • Post-transplantation • Acute Graft versus Host Disease • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Myelofibrosis • Transplantation

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

Orca Bio to Present New Clinical Data on Its High-Precision Cell Therapies at the 2026 Tandem Meetings of ASTCT and CIBMTR (Businesswire) - "The presentations will include data on the company's pipeline of investigational allogeneic T-cell immunotherapies for the treatment of multiple hematological malignancies, including Orca-T, Orca-Q and the Orca-T and allogeneic CAR-T combination therapy, OrCAR-T."

Clinical data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Graft versus Host Disease • Leukemia • Myelodysplastic Syndrome

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

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

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