Orca-T (Orca Bio)

Precision-T study met the primary endpoint of a statistically significant improvement in survival free of moderate-to-severe chronic graft versus host disease (cGvHD), showing 78% with Orca-T versus 38% with conventional allogeneic stem cell transplant (alloHSCT) at one year (HR 0.26, p<0.00001) Overall survival with Orca-T was 94% compared to 83% with alloHSCT at one year, and the cumulative incidence of moderate-to-severe cGvHD was 13% versus 44%, respectively Orca Bio is preparing to submit these findings in a BLA to the U.S. FDA in 2025 Results will be presented at the 51st Annual Meeting of the EBMT MENLO PARK, CA, USA I March 17, 2025 I Orca Bio, a late-stage biotechnology company committed to transforming the lives of patients through high-precision cell therapy, today announced positive results from the pivotal Phase 3 Precision-T study of Orca-T, its lead investigational allogeneic T-cell immunotherapy, in patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), high-risk myelodysplastic syndrome (MDS) and mixed-phenotype acute leukemia (MPAL). Orca-T is manufactured using highly purified regulatory T-cells, hematopoietic stem cells and conventional T-cells derived from peripheral blood from either related or unrelated matched donors. In the randomized Precision-T study, Orca-T met the primary endpoint of a statistically significant improvement in survival free of moderate-to-severe chronic graft versus host disease (cGvHD) with Orca-T. At one year, the rate for patients who received Orca-T was 78% compared to 38% for patients who received a conventional allogeneic hematopoietic stem cell transplant (alloHSCT). Patients in the Orca-T group achieved an estimated overall survival (OS) of 94% compared to 83% in the alloHSCT arm at one year. “Today, treating patients with serious blood cancers using allogeneic stem cell transplants requires a difficult risk-benefit trade-off as clinicians aim to cure the disease while avoiding potentially deadly treatment-related toxicities, like GvHD,” said presenting author Everett Meyer, M.D., Ph.D., hematologist and associate professor of medicine in Blood and Marrow Transplantation and Cellular Therapy at Stanford Health Care. “The Precision-T study showed double the rate of survival free from GvHD with Orca-T versus a conventional transplant, a relapse-free survival rate of 76% and no new safety concerns. These findings are highly encouraging and provide compelling new evidence as we work to solve for the critical factors contributing to the needs of this patient population.” Precision-T Study Results In the study, all patients (n=187) with a median age of 43.5 years (range 19-65 years) were randomized 1:1 to Orca-T plus single-agent tacrolimus (TAC) or alloHSCT plus TAC methotrexate (TAC/MTX). Patients across both groups received myeloablative conditioning (MAC) and used a related or unrelated matched donor. Patients had a median follow-up time of 11.4 months (range 0.2-24.3 months) across both arms. Key results from the Precision-T study at one year are summarized below: Exploratory endpoints at one year include the rate of relapse-free survival which was 76% and 74% in the Orca-T and alloHSCT arms, respectively (HR 0.80, p=0.49). The cumulative incidence of non-relapse mortality was 3% in the Orca-T arm and 13% in the alloHSCT arm. Additionally, the cumulative incidence of Grade 3 or 4 acute GvHD was 6% and 17% in the Orca-T and alloHSCT arms, respectively. No new safety issues were identified with Orca-T. Grade ≥ 4 infections per CTCAE scoring were noted in 6% and 10% of patients in the Orca-T and alloHSCT arms, respectively. Orca-T was manufactured in Orca Bio’s centralized GMP facility and delivered to patients at 19 treatment centers across the U.S., with all infusions occurring within a vein-to-vein time of 72 hours or less. “Approximately 46,000 people are diagnosed with AML, ALL and MDS in the U.S. each year, but only a fraction of them receive an allogeneic stem cell transplant within the current paradigm,” said Rawan Faramand, M.D., Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center. “Additional treatment options are needed, and the introduction of a cell therapy like Orca-T that leverages a precision-based approach could pave the way for a new standard of care for patients with various hematologic malignancies.” “These exciting results underscore Orca Bio’s vision of transforming the treatment landscape for patients living with serious blood cancers, potentially standardizing curative treatment for diseases like AML, ALL and MDS,” said Ivan Dimov, Ph.D., co-founder and chief executive officer at Orca Bio. “We are working closely with the FDA and expect to submit a Biologics License Application this year. These results support the validity of our high-precision platform as we continue to advance our robust pipeline of allogeneic cell therapies for the treatment of hematologic malignancies, autoimmune diseases and beyond.” Orca Bio is grateful to the patients and families, donors and trial site investigators who participated in the Precision-T study. The complete results will be presented on April 2, 2025, at the 51st Annual Meeting of the EBMT in Florence, Italy. About Precision-T Precision-T (NCT05316701) is a randomized, open-label multi-center study that evaluated the safety, efficacy and tolerability of Orca Bio’s lead investigational allogeneic T-cell immunotherapy, Orca-T, compared to 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 Orca-T in patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), high-risk myelodysplastic syndrome (MDS) and mixed-phenotype acute leukemia (MPAL). There are 19 leading treatment centers participating in the trial, which enrolled 187 patients across the U.S. About Orca-T Orca-T is an investigational allogeneic T-cell immunotherapy being evaluated for the treatment of multiple hematologic malignancies. Orca-T is composed of highly purified regulatory T-cells, CD34+ stem cells and conventional T-cells derived from peripheral blood from either related or unrelated matched donors. Orca-T has received Regenerative Medicine Advanced Therapy (RMAT) and Orphan Drug Designation for the prevention of graft versus host disease or death in patients eligible for hematopoietic stem cell transplant from the U.S. Food and Drug Administration. About Orca Bio Orca Bio is a late-stage biotechnology company developing high-precision cell therapies for the treatment of cancer and autoimmune diseases. Our 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. 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 www.orcabio.com . SOURCE: Orca Bio

Orca Bio on Monday said its T cell therapy, when used in people with certain blood cancers, reduced the risk of treatment complications seen with bone marrow transplants. The company now plans to apply for FDA approval later this year. The private California biotech’s cell therapy, named Orca-T, cut the risk of moderate-to-severe chronic graft-versus-host disease or death by 74% at one year compared to conventional bone marrow transplant, meeting the key endpoint of a Phase 3 study. Also, an interim survival analysis showed that 94% of patients in the Orca-T arm were alive, compared to 83% of those who received a conventional bone marrow transplant, though results were not yet statistically significant. Bone marrow transplants, which are typically used to treat or potentially cure certain blood cancers, come with the significant risk of graft-versus-host disease, a complication where the donor cells attack a patient’s own cells. Graft-versus-host disease comes in two forms: acute and chronic. The chronic form, which typically develops months after the transplant, can cause long-term debilitating symptoms all over the body, including rash, joint pain, muscle weakness and more. “We can potentially break free from that deadly trade-off that patients and physicians are going through every day” between treating cancers and long-term complications, Orca co-founder and CEO Ivan Dimov told Endpoints News in an interview ahead of the data release. Dimov is an alum of the Irv Weissman lab at Stanford, from which Orca’s technology is licensed. Orca-T comes as three components instead of one, Dimov said. Alongside blood stem cells, Orca also infuses highly purified regulatory T cells. Then, a few days later, it infuses conventional T cells, which are reined in by the regulatory T cells but can still fight infections and cancer. Relapse-free survival at one year was 76% and 74% in the Orca-T and conventional transplant arms, respectively. As for safety, Orca noted that 6% of patients who received Orca-T experienced Grade≥4 infections, while 10% of patients who got blood stem cell transplants did. The Phase 3 study included 187 patients with several forms of blood cancer: acute myeloid leukemia, acute lymphoblastic leukemia, high-risk myelodysplastic syndrome and mixed-phenotype acute leukemia. The cells for both conventional and Orca’s blood stem cell transplants come from either related or unrelated matched donors. In the Phase 3 study, the donor cells were sent to Orca’s central manufacturing site, where the therapy was manufactured and then delivered to one of 19 sites in the US where the study was conducted. Orca said the vein-to-vein time for all infusions was 72 hours or less. A key difference between conventional transplants and Orca’s cell therapy is the latter is classified as a drug — meaning it has to be paid for as one by the hospitals and then reimbursed by insurers — and could be expensive. Dimov said that Orca has been working with payers “for a while now,” and that it believes that reducing toxicities can offset a lot of costs. Orca Bio declined to say what it’s planning to charge, saying it’s premature to talk about price.