MENLO PARK, CA, December 6, 2025 – Orca Bio, a late-stage biotechnology company committed to transforming the lives of patients through high-precision cell therapy, today announced new data presented on its lead investigational allogeneic T-cell immunotherapy, Orca-T, at the 67th American Society of Hematology (ASH) Annual Meeting. 

Orca-T with Reduced Intensity Conditioning 

The new results of a single-center, open-label Phase 1 investigator-sponsored trial evaluating Orca-T in patients aged 60-75 (median 68 years) with a reduced intensity conditioning regimen (RIC) for the treatment of acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), myelodysplastic syndrome (MDS) and myeloproliferative neoplasm (MPN) showed a low incidence of both acute and chronic graft versus host disease (aGvHD, cGvHD) while maintaining a low rate of disease relapse. 

“Many older patients with hematological malignancies are not eligible for myeloablative allogeneic stem cell transplant due to the significant toxicities associated with it. A conventional reduced intensity alloHSCT can be safer and more tolerable, but it may also reduce the curative potential,” said Everett Meyer, M.D., Ph.D., hematologist and associate professor of medicine in Blood and Marrow Transplantation and Cellular Therapy at Stanford Health Care. “These early results suggest Orca-T following reduced intensity conditioning may preserve a meaningful graft-versus-leukemia effect while achieving low rates of toxicities, including acute and chronic GvHD. While additional research is needed, these findings support Orca-T as a potentially feasible option for older adults with blood cancer.” 

Highlighted in an oral session, patients (n=46) with 8/8 matched donors were conditioned with fludarabine/melphalan/total body irradiation (TBI) (n=11) or fludarabine/thiotepa/TBI (n=12). Conditioning was further reduced where 23 patients were enrolled in a cohort eligible for outpatient treatment. Also included in the analyses was a cohort of patients (n=7) with 7/8 matched donors receiving fludarabine/thiotepa/TBI.  

All patients (n=53) had successful neutrophil engraftment at a median of 15 days (range 9-39). At one year, there was no aGvHD grade 3-4 observed, and the rate of aGvHD grade 2 was 12.3% (95% CI, 5-23%). The rate of moderate-to-severe cGvHD was 9.6% (95% CI, 3-21%). At one year, relapse-free survival (RFS) and graft versus host disease relapse-free survival (GRFS) were 82% (95% CI, 72-94%) and 72% (95% CI, 60-87%), respectively. The overall survival (OS) was 88% (95% CI, 79-98%) and non-relapse mortality (NRM) was 10% (95% CI, 4-20%). The outpatient-eligible cohort experienced NRM of 0%, RFS of 80% (95% CI, 65-100%) and OS of 95% (95% CI, 87-100%). 

“We are energized by these new data, which reinforce our belief that Orca-T has the potential to expand curative treatment options to many more people living with serious blood cancers, including those who may not be eligible for a myeloablative transplant today, and even patients treated in the outpatient setting,” said Nate Fernhoff, Ph.D., co-founder and chief executive officer at Orca Bio. “Our Serene-T Phase 2 study evaluating Orca-T with RIC recently opened for enrollment and is the next step towards understanding if Orca-T may provide a path to treatment for more patients in need of therapeutic options.” 

New Analyses from the Precision-T Phase 3 Study 

Retrospective Comparison of Orca-T versus PTCy-Based GvHD Prophylaxis 

An observational analysis compared a dataset derived from patients who received Orca-T in the Precision-T Phase 3 study (n=45) to a historical PTCy patient cohort (n=475) derived from the Center for International Blood and Marrow Transplant Research (CIBMTR).  

At one year, OS was 94% with Orca-T compared to 81% with PTCy. RFS was 86% and 70% for Orca-T and PTCy, respectively. There was 0% NRM with Orca-T and 9.7% with PTCy, which achieved statistical significance. There was 13.8% relapse in the Orca-T cohort and 21% in the PTCy cohort. The rate of cGvHD was 14.7% with Orca-T versus 8.2% with PTCy. Of note, the OS in patients over the age of 50 was 100% with Orca-T compared to 75% with PTCy. 

These outcomes were achieved using only single-agent tacrolimus for pharmacological GvHD prophylaxis for Orca-T recipients, in contrast to the triple-agent regimen used with PTCy, implicating the potential role of immune reconstitution in both disease control and mitigating posttransplant complications. 

Orca-T Improved GvHD-free Survival Across Patient Demographics 

In subset analyses from the Precision-T Phase 3 study comparing Orca-T to a conventional alloHSCT plus tacrolimus and methotrexate (Tac/MTX), Orca-T demonstrated improved clinical outcomes overall and across subgroups with varied demographic and clinical features. For all patients, the rate of survival free from cGvHD (cGFS) was 78% and 38% for Orca-T and Tac/MTX, respectively. For patients over the age of 50, the rate of cGFS was 74% and 35% for Orca-T and Tac/MTX, respectively. For all patients, the rate of GRFS was 63% and 31% for Orca-T and Tac/MTX respectively, and 59% and 23% for patients over the age of 50 with Orca-T and Tac/MTX, respectively. 

Notably, OS and NRM were similar for patients aged 51-65 as in the entire safety population. For patients over the age of 50 at one year, OS was 94% (77%, 98%) for Orca-T patients (n=31) versus 80% (61%, 91%) for Tac/MTX patients (n=32) (HR=0.48 [0.12, 1.89]). Rates of NRM were 6.5% (1.1%, 19%) with Orca-T vs 16% with Tac/MTX (5.7%, 31%) (HR=0.49 [0.11, 2.06]). Together, these data suggest that the results of Orca-T extend to older patients and those with high-risk disease.  

Health-Related Quality of Life: Patient Reported Outcomes 

An exploratory endpoint from the Precision-T Phase 3 study evaluating health-related quality of life (HRQoL) and hospitalization patterns showed that Orca-T delivered marked improvements over conventional alloHSCT. 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.  

FACT-BMT total scores were consistently higher for Orca-T recipients across all time points, with Orca-T recipients exceeding baseline scores across physical well-being, functional well-being and transplant-specific subscales by day 100, while the alloHSCT arm did not surpass baseline until day 365. By day 365, Orca-T scores across these domains were higher by a magnitude of two or more compared to the control arm. 

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; HR 0.53 [0.32, 0.86]). 

“The additional analyses from our Phase 3 study further highlight Orca-T’s potential superiority across critical measures, from lower rehospitalization rates to improved outcomes in older patients,” said Scott McClellan, M.D., chief medical officer at Orca Bio. “These results continue to strengthen our conviction that Orca-T has the potential to transform the transplant experience and meaningfully raise the standard of care for patients and providers.” 

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.