Orca Bio Announces Orca-T® Phase 3 Data Published in Blood Demonstrate Significant Improvement in Survival Free from Chronic Graft versus Host Disease in Patients with Hematological Malignancies

Results from the Precision-T study showed Orca-T significantly improved survival free from chronic GvHD in patients with AML, ALL and MDS compared to a conventional allogeneic hematopoietic stem cell transplant

New findings demonstrate fewer rehospitalizations due to safety events and reduced rates of non-relapse mortality

Orca-T is the first Treg-based immunotherapy to demonstrate an improvement in patient outcomes including overall survival and GvHD and relapse-free survival (GRFS) in these conditions

Orca-T is being evaluated under Priority Review by the U.S. Food and Drug Administration (FDA) with a target action date of April 6, 2026

MENLO PARK, Calif.--(BUSINESS WIRE)--Orca Bio, a late-stage biotechnology company committed to transforming the lives of patients through high-precision cell therapy, today announced the publication of the Precision-T Phase 3 study results of its lead investigational allogeneic T-cell immunotherapy, Orca-T, in Blood, a journal of the American Society of Hematology (ASH). The study compared Orca-T to a conventional allogeneic hematopoietic stem cell transplant (alloHSCT) in patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), myelodysplastic syndrome (MDS) and mixed-phenotype acute leukemia (MPAL). These results were first presented on April 2, 2025, at the 51st Annual Meeting of The EBMT in Florence, Italy, and further analyses were presented at the 67th ASH Annual Meeting on December 6, 2025.

In the randomized Precision-T study, Orca-T plus single-agent tacrolimus (TAC) demonstrated a significant improvement in the primary endpoint of survival free from moderate-to-severe chronic graft versus host disease (cGFS) compared to alloHSCT plus tacrolimus/methotrexate (TAC/MTX). The rate for patients who received Orca-T was 78% (95% CI: 65%, 87%) compared to 38.4% (95% CI: 26%, 51%) for patients who received an alloHSCT (HR 0.26; p<0.00001), an improvement driven by a reduction in moderate-to-severe chronic graft versus host disease (cGvHD) and fewer patient deaths.

“Today, treating patients with serious blood cancers using conventional allogeneic stem cell transplants often forces a difficult risk–benefit trade-off, as clinicians work to cure the disease while avoiding life-threatening complications like GvHD,” said lead author Everett Meyer, M.D., Ph.D., hematologist and associate professor of medicine in Blood and Marrow Transplantation and Cellular Therapy at Stanford Medicine. “The Precision-T results showed that Orca-T can meaningfully shift that balance, delivering improved GvHD-free survival alongside less toxicity, including fewer serious infections and lower non-relapse mortality. Orca-T has the potential to become an important new therapy for patients and a valuable new option for the providers who care for them.”

In the study, all patients (n=187) with a median age of 43.6 years (range 19-65 years) were randomized 1:1 to Orca-T plus TAC or alloHSCT plus TAC/MTX. Patients across both groups received myeloablative conditioning 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. Additional results from the Precision-T study at one year include:

• A secondary endpoint of cumulative incidence of moderate-to-severe cGvHD was 12.6% (95% CI: 5%, 23%) and 44.0% (95% CI: 31%, 56%) in the Orca-T and alloHSCT arms, respectively (HR 0.19; p<0.00002).
• The overall survival (OS), another secondary endpoint, was 93.7% (95% CI: 86%, 97%) in the Orca-T arm and 83.2% (95% CI: 73%, 90%) in the alloHSCT arm (HR 0.49; p=0.11823).
• A secondary endpoint of GvHD and relapse-free survival (GRFS) was 63.1% and 30.9% with Orca-T and alloHSCT (p<0.001 in a post hoc analysis), respectively.
• The cumulative incidence of non-relapse mortality (NRM) was 3.4% (95% CI: 0.9%, 8.8%) for Orca-T versus 13.2% (95% CI: 6.8%, 21.6%) for alloHSCT (HR 0.27 [95% CI: 0.08, 0.93]; p=0.03 in a post hoc analysis).

Additional safety findings were consistent with previous studies. The cumulative incidence for grade III or IV acute GvHD at day +180 was reduced with Orca-T with 6.2% (95% CI: 2.3, 12.9) versus 16.5% (95% CI: 9.4, 25.3) with alloHSCT (HR 0.37 [95% CI: 0.13, 1.02]; p=0.044 in a post hoc analysis). Grade 3+ infections were less common with Orca-T, with a one-year estimated incidence of 8.4% (95% CI: 3.6%, 16%) for Orca-T and 16.1% (95% CI: 9.2%, 25%) for alloHSCT.

An exploratory endpoint evaluated health-related quality of life (HRQoL) and hospitalization patterns and found Orca-T delivered marked improvements over conventional alloHSCT. In the data presented at ASH 2025, patients receiving Orca-T experienced faster recovery to, and higher improvement above, baseline HRQoL, fewer ICU stays, lower likelihood of rehospitalization and higher rehospitalization-free survival, suggesting better early post-treatment recovery and a lower burden of GvHD symptoms.

Rehospitalizations due to adverse events occurred less frequently among Orca-T recipients (27.3% [24] vs. 45.7% [43]), with fewer total hospitalization days per patient (30.6 vs. 40.8). Rehospitalization-free survival at 18 months was also significantly improved with Orca-T, reaching 66.4% (95% CI: 54.0, 76.2) compared to 33.8% (95% CI: 18.5, 49.9) for conventional alloHSCT (p=0.0096 in a post hoc analysis; HR 0.53 [0.32, 0.86]).

“As the first Treg-based immunotherapy to show improved outcomes for patients with acute leukemias and myelodysplastic syndrome compared with a conventional transplant, Orca-T has the potential to become a new standard of care,” said Nate Fernhoff, Ph.D., co-founder and chief executive officer at Orca Bio. “The Phase 3 results published in Blood underscore our ability to potentially redefine how blood cancers are treated today. We look forward to continuing to work closely with the FDA on the review of our application with the goal of making Orca-T available to patients who need it.”

The safety and efficacy of Orca-T have not been determined by any regulatory authority. Orca-T is currently being evaluated under Priority Review by the U.S. Food and Drug Administration (FDA) with a Prescription Drug User Fee Act (PDUFA) target action date of April 6, 2026.

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 under evaluation for the treatment of multiple hematologic malignancies including acute leukemias and myelodysplastic syndromes. Orca-T is composed of highly purified regulatory T-cells, hematopoietic stem cells and conventional T-cells derived 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 (FDA). The Biologics License Application (BLA) for Orca-T is currently under Priority Review with the FDA with a Prescription Drug User Fee Act (PDUFA) target action date of April 6, 2026.

About Orca Bio

Orca Bio is a late-stage biotechnology company developing high-precision cell therapies for the treatment of blood cancer and autoimmune diseases. The company’s manufacturing platform uses single-cell precision to create personalized cell therapy products intended 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.

Trademarks or registered trademarks used in this press release are the property of their respective owners.

Corporate Communications
Kelsey Grossman
media@orcabio.com

Investor Relations
Joshua Murray
ir@orcabio.com