Orca-T / Orca Biosystems - LARVOL DELTA

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

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

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

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

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

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

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

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

Orca Bio to Present Clinical Data on Its Pipeline of High-Precision Cell Therapies at the 52nd Annual Meeting of the EBMT (Businesswire) - "Patient reported outcomes with Orca-T from the pivotal Precision-T Phase 3 study will be presented including quality of life and rates of rehospitalizations compared to conventional alloHSCT; Data evaluating the use of Orca-T with reduced intensity conditioning versus PTCy for the treatment of hematologic malignancies will be shared; Additional presentations will highlight the manufacturing and nationwide distribution data reported on Orca–T and clinical findings of Orca-Q in patients with haploidentical donors."

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

Regulatory-like FOXP3+Helios+ CD4+ T conventional cells correlate with T cell activation after Orca-T immunotherapy. (PubMed, Blood) - "Further, we discovered that this T cell subset possessed a regulatory-like phenotype and correlated significantly with the frequencies of activated CD4+ and CD8+ T cell populations 3 months post-treatment, regardless of which therapy patients received. Overall, this study identifies a novel T cell subset which is enriched very early after cellular therapy for leukemia and may be predictive of long-term immune activation after Orca-T and PBSC-derived T cell infusion."

IO biomarker • Journal • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Oncology • Transplantation • CD4 • CD8 • FOXP3 • IL2RA • ISG20

Caregiver Meaningful Score Differences and Meaningful Score Regions for the Observer-Reported Communication Ability (ORCA) Measure for Individuals with Angelman Syndrome. (PubMed, Value Health) - "We present a novel anchor-based methodological approach for deriving MSD and MSR thresholds for clinical outcome assessments. While these MSD and MSR estimates for the ORCA measure are preliminary, our methods offer a strategy for establishing meaningful change thresholds in rare disease populations where traditional longitudinal methods may be challenging to implement."

Journal • Rare Diseases

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

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