OrcaGraft (engineered donor allograft cell therapy) / Orca Biosystems - LARVOL DELTA

Preliminary safety and efficacy of myeloablative orca-q with tacrolimus or without graft-versus-host disease prophylaxis for treatment of advanced hematologic malignancies (ASH 2025) - P1 | "Preventing GVHD followingalloHSCT typically requires multi-agent immunosuppression, commonly involving methotrexate or post-transplant cyclophosphamide (PTCy) in combination with a calcineurin inhibitor and other agents.However, pharmacologic immunosuppression impairs immune reconstitution and heightens the risk oforgan toxicity, infection, and disease relapse. The low infection rates observed suggest that the cellular composition of Orca-Qcan control GVHD and accelerate immune reconstitution even without pharmacologicalimmunosuppression. The Phase 1 study continues to enroll patients to further confirm these results."

Clinical • Metastases • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Chronic Lymphocytic Leukemia • Chronic Myeloid Leukemia • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Myelofibrosis • Oncology • CD4 • CD8

Orca-Q with and Without the Use of GvHD Prophylaxis (Businesswire) - "Median time to neutrophil engraftment was 15 days for patients who received tac and 11 days for patients who did not. Orca-Q was well-tolerated with 94% overall survival (OS) at one year for patients with tac and 87% for patients without tac. At one year, GvHD-and-relapse-free survival (GRFS) was 77% with tac and 79% without tac, and NRM was 6% and 0% with tac and without tac, respectively. Relapse-free survival (RFS) at one year was 88% with tac and 87% without tac. At Day 180, moderate-to-severe chronic GvHD was 12% with tac and 0% without tac."

P1 data • Acute Myelogenous Leukemia • B Acute Lymphoblastic Leukemia • Chronic Myeloid Leukemia • Myelodysplastic Syndrome • Myelofibrosis

Preliminary Safety and Efficacy of Myeloablative Orca-Q with No GvHD Prophylaxis for Treatment of Advanced Hematologic Malignancies (ASH 2024) - P1 | "Prevention of GvHD after alloHSCT routinely necessitates multi-agent immunosuppression consisting of either methotrexate or post-transplant cyclophosphamide (PTCy) combined with a calcineurin inhibitor and additional drugs...All patients received myeloablative conditioning, either busulfan/fludarabine/thiotepa (BFT; n=11) or total body irradiation-based (TBI; n=3)...One patient received TBI/etoposide and experienced grade 3 aGvHD that was treated to resolution...BFT conditioning has shown promising disease control with Orca-T (Salhotra et al...Disease control may be further augmented by BFT conditioning. The Orca-Q Phase 1 study continues to enroll patients across the US."

Clinical • Metastases • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Chronic Lymphocytic Leukemia • Chronic Myeloid Leukemia • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Myelofibrosis • Oncology • HLA-B • HLA-C • HLA-DRB1

Safety and Efficacy of Orca-Q with Haploidentical Donors for the Treatment of Advanced Hematologic Malignancies without the Use of Post-Transplant Cyclophosphamide (ASH 2023) - P1 | "RESULTS Orca-Q was successfully manufactured and delivered to all subjects with a vein-to-vein time (time between end of donor apheresis to start of recipient's Orca-T infusion) of < 72 hours...Sixteen patients received TBI-based MAC; 17 received busulfan-based MAC (Table)...With median follow-up of approximately 1 year, no patients experienced moderate or severe cGvHD, the low AE profile in the haplo setting remains favorable, and 1 year GvHD-free, relapse-free survival of 83% is very encouraging. This phase 1 study continues to enroll patients across the US."

Clinical • Metastases • Post-transplantation • Acute Graft versus Host Disease • Cardiovascular • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Mucositis • Oncology • Transplantation • CD34 • HLA-DRB1

Orca Bio to Present New Clinical Data on Its High-Precision Cell Therapies at the 67th American Society of Hematology Annual Meeting (Businesswire) - "New data evaluating Orca-T with reduced intensity conditioning for the treatment of hematological malignancies in patients 60 to 75 years of age; Clinical findings of Orca-Q with and without the use of GvHD prophylaxis in patients with hematological malignancies including AML, ALL and MDS; Expanded feasibility data on the combination of Orca-T and an allogeneic CAR-T (OrCAR-T) in patients with high-risk B-ALL; Additional presentations will highlight overall survival and non-relapse mortality with Orca-T versus PTCy, and additional subsets from the pivotal Phase 3 study including relapse-free survival and patient-reported outcomes....Orca-T is currently under Priority Review with the FDA with a PDUFA target action date of April 6, 2026."

Clinical data • PDUFA • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • B Acute Lymphoblastic Leukemia • Myelodysplastic Syndrome

OGFT001-001: A Phase 1 Study of Orca-Q in Recipients Undergoing Allogeneic Transplantation for Hematologic Malignancies (clinicaltrials.gov) - P1 | N=300 | Recruiting | Sponsor: Orca Biosystems, Inc. | N=186 ➔ 300 | Trial completion date: Apr 2028 ➔ Dec 2027 | Trial primary completion date: Apr 2026 ➔ Dec 2027

Enrollment change • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation

Future Directions in Allogeneic Stem Cell Transplantation in Acute Lymphoblastic Leukemia. (PubMed, Acta Haematol) - "Innovative graft manipulation strategies, such as Orca-T and Orca-Q, aim to enhance graft-versus-leukemia (GVL) effects while minimizing graft-versus-host disease (GVHD). Key Messages ASCT remains a critical treatment for high-risk ALL, with advancements in conditioning, graft engineering, and post-transplant strategies. Future focus will be on optimizing patient selection, use in post CAR-T consolidation, and refining graft manipulation, aiming to personalize ASCT and enhance survival and quality of life for ALL patients."

Journal • Review • Acute Lymphocytic Leukemia • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Oncology • Transplantation

A Study of Allogeneic Hematopoietic Cell Transplantation for Primary Progressive Multiple Sclerosis (clinicaltrials.gov) - P1 | N=10 | Not yet recruiting | Sponsor: Stanford University

New P1 trial • CNS Disorders • Multiple Sclerosis • Transplantation

Haploidentical transplantation: An optimal platform for graft manipulation and cellular therapies. (PubMed, Blood Rev) - "Advances in in vivo graft manipulation techniques, such as post-transplant cyclophosphamide (PTCy) and ex vivo approaches, including TCRα/β and CD19 depletion, have shown promise in reducing the risk of severe GvHD without increasing the relapse rates. Innovative strategies, such as haploidentical donor lymphocyte infusions, "suicide-switch" mechanisms, ORCA-Q product infusions, and CAR based therapies offer potential to further optimize outcomes. This review examines the graft manipulation modalities in the haplo-HCT setting, highlighting their role in advancing cellular therapies and providing new hope in the fight against life-threatening diseases."

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

Preliminary Safety and Efficacy of Myeloablative Orca-Q with No GvHD Prophylaxis for Treatment of Advanced Hematologic Malignancies (TCT-ASTCT-CIBMTR 2025) - P1 | "Preventing GvHD often requires immunosuppressive drugs like methotrexate or post-transplant cyclophosphamide (PTCy), which can impair immune recovery and increase risks of organ damage, infections, and relapse...Patients received either busulfan/fludarabine/thiotepa (BFT; n=11) or total body irradiation-based (TBI; n=3) conditioning, and no post-therapy immunosuppression...One patient who received TBI/etoposide experienced grade 3 aGvHD and subsequently developed secondary graft loss, but no disease relapse...BFT conditioning has shown promising disease control with Orca-T (Salhotra et al...Disease control may be further augmented by BFT conditioning. The Orca-Q phase 1 study continues to enroll patients across the US."

Clinical • Metastases • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Oncology

Orca-Q Shows Promise in High-Risk Hematologic Cancers and BFT Conditioning May Synergize With the Agent (OncLive) - P1 | N=186 | NCT03802695 | Sponsor: Orca Biosystems, Inc. | "The precision-engineered allogeneic T-cell immunotherapy Orca-Q demonstrated rapid immune reconstitution with a low risk of infection in patients with high-risk hematologic malignancies who underwent myeloablative conditioning for allogeneic hematopoietic stem cell transplantation (HSCT) with HLA-identified donors in an ongoing phase 1 study (NCT03802695)....The 1-year overall survival (OS) rate was 85% (95% CI, 52%-98%) among patients who received Orca-Q (n = 14) in the phase 1 trial. Additionally, patients experienced a 1-year relapse-free survival (RFS) rate of 85% and GVHD-free RFS (GRFS) rate of 77%. The neutrophil and platelet engraftment rate was 100% with a median time of 11 days (range, 10-19).

P1 data • Acute Myelogenous Leukemia • B Acute Lymphoblastic Leukemia • Chronic Myeloid Leukemia • Myelodysplastic Syndrome • Myelofibrosis

Orca-Q Leads to Low Rates of GVHD, Non-Relapse Mortality in High-Risk Hematologic Malignancies After Allo-HCT (OncLive) - "'The early results [from the dose-expansion trial] are very promising, and the idea of having regimen free of GVHD [prophylaxis] is almost like a dream for our transplanters,' lead study author Mehrdad Abedi, MD, said in an interview with OncLive. 'We know about all the morbidity and mortality of the prophylactic regimen. Having very little or no GVHD and no transplant-related mortality is very significant.'"

Interview

Orca-Q Leads to Low Rates of GVHD, Non-Relapse Mortality in High-Risk Hematologic Malignancies After Allo-HCT (OncLive) - P1 N=186 | NCT03802695 | Sponsor: Orca Biosystems, Inc. | "...no instances of primary graft failure were reported in any patients in arm C (n = 14); 1 patient (7%) experienced secondary graft failure. Mild chronic GVHD (cGVHD) was reported in 1 patient (7%), and no patients had moderate-to-severe cGVHD...Regarding efficacy, the 1-year overall survival (OS) rate was 85% (95% CI, 52%-96%). The 1-year relapse-free survival (RFS) and GVHD RFS (GRFS) rates were 85% and 77%, respectively...In the subgroup of patients who underwent BFT myeloablative conditioning (n = 11), no instances of primary or secondary graft failure were reported. No patients in this subgroup experienced cGVHD; 2 patients (18%) had grade 2 aGVHD, but no patients had grade 3 aGVHD. No grade 2 or 3 infections were reported in this group, and the non-relapse mortality rate was 0...Enrollment in the phase 1 trial is ongoing in the United States."

P1 data • Acute Myelogenous Leukemia • B Acute Lymphoblastic Leukemia • Myelodysplastic Syndrome • Myelofibrosis

Orca Bio to Present Clinical Data on Its High-Precision Cell Therapies at the 66th American Society of Hematology Annual Meeting (Businesswire) - "Three-year survival data with Orca Bio’s lead investigational allogeneic T-cell immunotherapy, Orca-T, will be presented from the multicenter Phase 1b clinical trial of patients with acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL) and high-risk myelodysplastic syndrome (MDS). Additionally, initial feasibility, safety and efficacy data from an investigator-sponsored trial evaluating the combination of Orca-T with allogeneic CD19/CD22-CAR-T cells in patients with high-risk B-cell acute lymphoblastic leukemia (B-ALL) will be shared. In a third oral session, data from a multicenter Phase 1 clinical trial will be presented from patients treated with Orca Bio’s second-generation investigational allogeneic T-cell immunotherapy, Orca-Q, in patients with hematologic malignancies without the use of any post-treatment graft versus host disease (GvHD) prophylaxis."

Clinical data • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

OGFT001-001: A Phase 1 Study of Orca-Q in Recipients Undergoing Allogeneic Transplantation for Hematologic Malignancies (clinicaltrials.gov) - P1 | N=186 | Recruiting | Sponsor: Orca Biosystems, Inc. | Trial completion date: Apr 2026 ➔ Apr 2028 | Trial primary completion date: Apr 2024 ➔ Apr 2026

Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myelofibrosis • Oncology • Transplantation

Orca Bio Presents Positive Data Demonstrating the Potential for Orca-T and Orca-Q to Expand Treatment to Additional Patient Groups at the 65th ASH Annual Meeting (Businesswire) - P1 | N=186 | NCT03802695 | Sponsor: Orca Biosystems, Inc. | "In an oral presentation, Orca Bio shared updated data from a multi-center Phase 1 clinical trial of its second high-precision cell therapy, Orca-Q, in patients with a haploidentical donor without the use of post-transplant cyclophosphamide (PTCy)....The positive outcomes from an expanded group of 33 patients with AML, ALL and CML support Orca-Q as a potential treatment option for patients with a haploidentical donor. With a median of 375 days follow-up, updated safety and efficacy data include: No patients experienced moderate-to-severe chronic GvHD (0%). There was one event of grade 3 acute GvHD and no grade 4 acute GvHD. NRM was 9%. RFS, GRFS and OS at one year were 82%. Additionally, no new safety signals were identified."

P1 data • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Chronic Graft versus Host Disease • Chronic Myeloid Leukemia

Orca‑Q Demonstrates Favorable Graft‑Versus‑Host Disease (GvHD) and Relapse‑Free Survival With Haploidentical Donors Without Post‑Transplant Cyclophosphamide (SOHO 2023) - P1 | "Background: Allogeneic stem cell transplantation (SCT) can be curative for high-risk (HR) hematologic malignancies, but until recently, access was limited to fully matched donors. Our findings suggest encouraging safety and efficacy outcomes using Orca-Q cell therapy for haplo-SCT, without PTCy, and only single agent tacrolimus. Patients treated with Orca-Q experienced a low adverse event profile, low incidence of overall and severe aGvHD/cGvHD, and improved GRFS. This phase 1 study continues to enroll patients across the US."

Post-transplantation • Acute Myelogenous Leukemia • Chronic Myeloid Leukemia • Hematological Malignancies • Oncology • ARNTL • CD34 • HLA-DRB1

Phase I/II Trial: Engineered Donor Graft (Orca Q) for Pediatric Hematopoietic Cell Transplant (HCT) (clinicaltrials.gov) - P1/2 | N=40 | Recruiting | Sponsor: University of Florida | Suspended ➔ Recruiting

Enrollment open • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • Pediatrics • Transplantation • HLA-B • HLA-C • HLA-DRB1

Advances in graft-versus-host disease prevention strategies: latest updates from the 2022 ASH annual meeting. (PubMed, Exp Hematol Oncol) - "The use of innovative agents and regimens, along with the conventional prophylactic approach of combining post-transplant cyclophosphamide and anti-thymocyte globulin, were discussed. The innovative agents and regimens highlighted in this review include abatacept, the first FDA-approved drug for acute GvHD prophylaxis; RGI-2001, which promotes the expansion of regulatory T cells; and cell therapies such as Orca-T and Orca-Q. These advancements provide promising strategies and options for GvHD prevention, offering hope for improved post-transplant patient outcomes in terms of survival rates."

Journal • Acute Graft versus Host Disease • Bone Marrow Transplantation • Graft versus Host Disease • Immunology • Transplantation

Phase I/II Trial: Engineered Donor Graft (Orca Q) for Pediatric Hematopoietic Cell Transplant (HCT) (clinicaltrials.gov) - P1/2 | N=40 | Suspended | Sponsor: University of Florida | Recruiting ➔ Suspended

Trial suspension • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Pediatrics • Transplantation • HLA-B • HLA-C • HLA-DRB1

Orca-Q Demonstrates Favorable GvHD-and-Relapse-Free Survival with Haploidentical Donors without Post-Transplant Cyclophosphamide (TCT-ASTCT-CIBMTR 2023) - P1 | "Patients treated with Orca-Q experienced a low adverse event profile, low incidence of overall and severe aGvHD/cGvHD, and an improved GRFS rate. This phase 1 study continues to enroll patients across the US."

Post-transplantation • Acute Graft versus Host Disease • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Chronic Myeloid Leukemia • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Oncology • Transplantation • ARNTL • CD34 • CSF3 • HLA-DRB1

A Phase 1 Study of Engineered Donor Grafts (Orca-Q) in Recipients Undergoing Allogeneic Transplantation for Hematologic Malignancies (clinicaltrials.gov) - P1 | N=186 | Recruiting | Sponsor: Orca Biosystems, Inc. | N=113 ➔ 186 | Trial completion date: Jul 2022 ➔ Apr 2026 | Trial primary completion date: Jul 2022 ➔ Apr 2024

Enrollment change • Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation

Orca-Q Demonstrates Favorable GvHD-and-Relapse-Free Survival in Haploidentical Transplants without Post-Transplant Cyclophosphamide (ASH 2022) - P1 | "Initial Orca-Q data demonstrates good clinical outcomes with single agent tacrolimus and no PTCy or MMF. Patients treated with Orca-Q experienced a low adverse event profile, low incidence and severity of both aGVHD and cGVHD, and improved GRFS rates, offering a potential new treatment option for patients undergoing haplo alloHSCT. This phase 1 study of Orca-Q continues to enroll patients with haplo donors across the US."

Acute Graft versus Host Disease • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Chronic Myeloid Leukemia • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Oncology • Respiratory Diseases • Transplantation • ARNTL • CD34 • CSF3 • HLA-B • HLA-DRB1

Orca Bio Presents Positive Data Reinforcing Clinical Profile of Orca-T and Orca-Q at 2023 Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR (Businesswire) - P1 | N=113 | NCT03802695 | Sponsor: Orca Biosystems, Inc. | "Orca Bio also presented findings from a Phase 1 multi-center trial of its second investigational cell therapy, Orca-Q, showing that patients with haploidentical – or half-matched – allogeneic hematopoietic stem cell donors, experienced no moderate-to-severe chronic GvHD (0%) and an improved GRFS rate (75%)."

P1 data • Acute Myelogenous Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

"Orca-Q Demonstrates Encouraging GRFS, Tolerability, and Low GVHD Incidence in Hematologic Cancers @cityofhope #leucsm https://t.co/85VSZUe6ac" (@OncLive)

Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Oncology