Precision-T: The first and only phase 3, randomized trial to demonstrate superiority over conventional alloHSCT + Tac/MTX in the MAC setting1

TREGZI doubled cGFS

TREGZI + Tac met the primary endpoint of superior cGFS vs conventional alloHSCT + Tac/MTX1

Kaplan-Meier curve showing one-year estimated incidence of cGFS. At one year, TREGZI + Tac was 78.0% and alloHSCT + Tac/MTX was 38.4%.Kaplan-Meier curve showing one-year estimated incidence of cGFS. At one year, TREGZI + Tac was 78.0% and alloHSCT + Tac/MTX was 38.4%.
*Log‑rank P value compares the Kaplan–Meier curves. Cox regression P value corresponds to the hazard ratio estimate.
†An event was defined as the development of moderate-to-severe chronic GVHD or death from any cause. The primary analysis was conducted at 56 total events.1

TREGZI significantly reduced cGVHD

Kaplan-Meier curve showing one-year estimated cGVHD. At one year, TREGZI + Tac was 12.6% and alloHSCT + Tac/MTX was 44.0%.Kaplan-Meier curve showing one-year estimated cGVHD. At one year, TREGZI + Tac was 12.6% and alloHSCT + Tac/MTX was 44.0%.

Moderate or severe cGVHD occurred in1:

  • 7 patients treated with TREGZI + Tac (6 moderate, 1 severe)
  • 30 patients treated with conventional alloHSCT + Tac/MTX (18 moderate, 12 severe)

TREGZI demonstrated 94% OS at 1 year

Kaplan-Meier curve showing one-year estimated OS. At one year, TREGZI + Tac was 93.9% and alloHSCT + Tac/MTX was 83.1%.Kaplan-Meier curve showing one-year estimated OS. At one year, TREGZI + Tac was 93.9% and alloHSCT + Tac/MTX was 83.1%.

OS results are descriptive and conclusions cannot be drawn.

TREGZI improved GRFS

Kaplan-Meier curve showing one-year estimated GRFS. At one year, TREGZI + Tac was 63.1% and alloHSCT + Tac/MTX was 30.9%.Kaplan-Meier curve showing one-year estimated GRFS. At one year, TREGZI + Tac was 63.1% and alloHSCT + Tac/MTX was 30.9%.

GRFS results are descriptive and conclusions cannot be drawn.

TREGZI improved survival free of chronic GVHD1
AlloHSCT, allogeneic hematopoietic stem cell transplant; cGFS, survival free from moderate-to-severe chronic GVHD; cGVHD, chronic GVHD; CI, confidence interval; GRFS, GVHD- and relapse-free survival; GVHD, graft-versus-host disease; HCT, hematopoietic cell transplantation; HR, hazard ratio; MAC, myeloablative conditioning; MTX, methotrexate; NRM, non-relapse mortality; OS, overall survival; Tac, tacrolimus.

TREGZI reduced the cumulative incidence of NRM2

Estimated cumulative incidence at 1 year

Infographic showing NRM. At one year, NRM with TREGZI + Tac was 3.4% vs 11.7% with conventional alloHSCT + Tac/MTXInfographic showing NRM. At one year, NRM with TREGZI + Tac was 3.4% vs 11.7% with conventional alloHSCT + Tac/MTX

NRM results are exploratory and conclusions cannot be drawn.

Fewer patients treated with TREGZI experienced NRM2
AlloHSCT, allogeneic hematopoietic stem cell transplant; cGFS, survival free from moderate-to-severe chronic GVHD; cGVHD, chronic GVHD; GRFS, GVHD- and relapse-free survival; GVHD, graft-versus-host disease; MTX, methotrexate; NRM, non-relapse mortality; OS, overall survival; Tac, tacrolimus.

Precision-T: A multicenter phase 3 trial of patients with advanced hematological malignancies undergoing alloHSCT with TREGZI vs conventional allogeneic graft transplant1-4

ALL, AML, MDS, or MPAL patients (N=187)

Key eligibility:

  • Aged 18-65 years
  • Acute leukemias in CR or CRi; or MDS patients with no circulating blasts and <10% blasts in bone marrow
  • Planned to undergo MAC
  • Adequate organ function, HCT-CI ≤4, and DRI intermediate or high; performance status: KPS ≥70%
  • All donors, related and unrelated, were 8/8 matched at HLA-A, HLA-B, HLA-C, and HLA-DRB1 alleles by high-resolution DNA-based typing
Schematic showing the Precision-T study design. Patients were randomized 1:1 to receive either TREGZI + Tac (n=93) or PBSC + Tac/MTX (n=94). At Days -10 through -2, both arms received myeloablative conditioning. TREGZI arm treatment regimen: Day 0, infusion of HSPCs and Tregs; Day +2 or Day +3, Infusion of Tcons; Day +3 Tac (5-10 ng/mL target). PBSC + Tac/MTX treatment regimen: Day -3, Tac (5-10 ng/mL target); Day 0, infusion of unmanipulated PBSCs; Days +1, +3, +6, +11, MTX prophylaxis.Schematic showing the Precision-T study design. Patients were randomized 1:1 to receive either TREGZI + Tac (n=93) or PBSC + Tac/MTX (n=94). At Days -10 through -2, both arms received myeloablative conditioning. TREGZI arm treatment regimen: Day 0, infusion of HSPCs and Tregs; Day +2 or Day +3, Infusion of Tcons; Day +3 Tac (5-10 ng/mL target). PBSC + Tac/MTX treatment regimen: Day -3, Tac (5-10 ng/mL target); Day 0, infusion of unmanipulated PBSCs; Days +1, +3, +6, +11, MTX prophylaxis.

No MTX, PTCy, or other additional immunosuppressive agents given with TREGZI

Primary endpoint

  • Rate of survival free from moderate-to-severe chronic GVHD in the 2 arms using a time-to-event‡ analysis (cGFS)

Secondary endpoints

Tested in the following hierarchical order:

  • Time to moderate-to-severe chronic GVHD
  • OS
  • GRFS§

Exploratory endpoints

  • RFS
  • NRM
*Per protocol, Tcons could be administered on Day +2 or +3; Tac was initiated the day after Tcon infusion.1
†MTX was administered as IV bolus at doses of 15 mg/m2 on Day +1 and 10 mg/m2 on Days +3, +6, and +11.1
‡An event was defined as the time from transplant (Day 0) to death by any cause or moderate-to-severe chronic GVHD, as graded by National Institutes of Health (NIH) consensus criteria and determined by an independent review committee.1
§Time to the earliest outcome of death, relapse, Grade 3 or 4 acute GVHD, or moderate-to-severe chronic GVHD.1

ALL, acute lymphoblastic leukemia; alloHSCT, allogeneic hematopoietic stem cell transplant; AML, acute myeloid leukemia; cGFS, survival free from moderate-to-severe chronic GVHD; CR, complete remission; CRi, complete remission with incomplete count recovery; DNA, deoxyribonucleic acid; DRI, disease risk index; GRFS, GVHD- and relapse-free survival; GVHD, graft-versus-host disease; HCT-CI, hematopoietic cell transplantation-specific comorbidity index; HLA, human leukocyte antigen; HSPC, hematopoietic stem and progenitor cells; IV, intravenous; KPS, Karnofsky performance scale; MAC, myeloablative conditioning; MDS, myelodysplastic syndrome; MPAL, mixed phenotype acute leukemia; MTX, methotrexate; NRM, non-relapse mortality; OS, overall survival; PBSC, peripheral blood stem cell; PTCy, post-transplant cyclophosphamide; RFS, relapse-free survival; Tac, tacrolimus; Tcon, conventional T cell; Treg, regulatory T cell.

Patient variables were well-balanced and representative of the general alloHSCT population1,3

Characteristics TREGZI + Tac (n=93) n (%) Conventional alloHSCT + Tac/MTX (n=94) n (%) Total
(N=187) n (%)
Age
Mean (years) 43.4 43.8 43.6
Aged ≥55 to ≤65 years 23 (24.7) 27 (28.7) 50 (26.7)
Sex
Male 53 (57.0) 50 (53.2) 103 (55.1)
Female 40 (43.0) 44 (46.8) 84 (44.9)
Race
American Indian or Alaska Native 1 (1.1) 2 (2.1) 3 (1.6)
Asian 10 (10.8) 8 (8.5) 18 (9.6)
Black or African American 1 (1.1) 2 (2.1) 3 (1.6)
Native Hawaiian or Other Pacific Islander 1 (1.1) 1 (1.1) 2 (1.1)
White/Caucasian 76 (81.7) 63 (67.0) 139 (74.3)
Not reported 4 (4.3) 18 (19.1) 22 (11.8)
Ethnicity
Hispanic or Latino 26 (28.0) 24 (25.5) 50 (26.7)
Not Hispanic or Latino 62 (66.7) 59 (62.8) 121 (64.7)
Not reported 5 (5.4) 11 (11.7) 16 (8.6)
Primary disease
ALL 30 (32.3) 27 (28.7) 57 (30.5)
AML 49 (52.7) 51 (54.3) 100 (53.5)
MDS 12 (12.9) 11 (11.7) 23 (12.3)
MPAL 2 (2.2) 5 (5.3) 7 (3.7)
Baseline HCT-CI score
0 18 (19.4) 27 (28.7) 45 (24.1)
1 30 (32.3) 18 (19.1) 48 (25.7)
2 22 (23.7) 20 (21.3) 42 (22.5)
3 11 (11.8) 21 (22.3) 32 (17.1)
4 12 (12.9) 7 (7.4) 19 (10.2)
5 0 1 (1.1) 1 (0.5)
DRI score
Intermediate 75 (80.6) 76 (80.9) 151 (80.7)
High/very high 18 (19.4) 18 (19.1) 36 (19.3)
Donor type
Matched sibling 46 (49.5) 49 (52.1) 95 (50.8)
Matched unrelated 47 (50.5) 45 (47.9) 92 (49.2)
Donor age
Mean ± SD (years) 37.5 ± 13.1 35.2 ± 12.4 36.4 ± 12.7
Aged ≥18 to <55 years 79 (84.9) 85 (90.4) 164 (87.7)
Aged ≥55 to ≤65 years 14 (15.1) 9 (9.6) 23 (12.3)
~20% of patients treated with TREGZI were in high-risk groups*
*As assessed by HCT-CI (≥3) and DRI high/very high scores.

ALL, acute lymphoblastic leukemia; alloHSCT, allogeneic hematopoietic stem cell transplant; AML, acute myeloid leukemia; cGFS, survival free from moderate-to-severe chronic GVHD; cGVHD, chronic GVHD; DRI, disease risk index; HCT-CI, hematopoietic cell transplantation-specific comorbidity index; HGRFS, GVHD- and relapse-free survival; GVHD, graft-versus-host disease; MAC, myeloablative conditioning; MDS, myelodysplastic syndrome; MPAL, mixed phenotype acute leukemia; MTX, methotrexate; NRM, non-relapse mortality; OS, overall survival; SD, standard deviation; Tac, tacrolimus.
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IMPORTANT SAFETY INFORMATION AND INDICATIONS AND USAGE

ISI tray

ISI tray

INDICATIONS AND USAGE

TREGZI is indicated for use in matched donor hematopoietic stem cell transplantation with myeloablative preparative regimen, for hematopoietic and immunologic reconstitution and to improve chronic graft-versus-host disease-free survival, in the treatment of adults with hematological malignancies.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Graft Failure: Graft failure has occurred after TREGZI administration. Screen TREGZI recipients for antidonor antibodies that may prevent engraftment. Monitor patients closely for laboratory evidence of hematopoietic recovery.

Graft-Versus-Host Disease: Acute and chronic Graft-Versus-Host disease (GVHD), including life-threatening and fatal cases, occurred following treatment with TREGZI. Acute GVHD manifests as maculopapular rash, gastrointestinal symptoms, and elevated bilirubin. Chronic GVHD may include skin rash, mouth sores, dry eyes, liver inflammation, and development of scar tissue in the skin and joints and damage to the lungs. Treat patients with a single agent calcineurin inhibitor as prophylaxis to decrease the risk of GVHD. Monitor for signs and symptoms of GVHD, and treat if GVHD develops.

Infusion Reactions: Infusion reactions (IRs) may occur during or following treatment with TREGZI. Serious hypersensitivity reactions including anaphylaxis may occur to DMSO, human serum albumin (HSA), Dextran or murine protein present in TREGZI. IRs may begin within minutes of the start of TREGZI infusion, although symptoms may continue to intensify and not peak for several hours after the completion of the infusion. Monitor patients for signs and symptoms of IRs during and after TREGZI administration. When a reaction occurs, pause the infusion and institute supportive care as needed. Premedicate patients with antipyretics and histamine antagonists prior to infusion to reduce the incidence and intensity of infusion reactions.

Secondary Malignancies and Malignancies of Donor Origin: Secondary malignancies and malignancies of donor origin may occur following treatment with TREGZI. Development of secondary malignancies, including posttransplantation lymphoproliferative disorder (PTLD) may occur many years after transplantation. PTLD manifests as a lymphoma-like disease favoring non-nodal sites. PTLD is usually fatal if not treated. Serial monitoring of blood for EBV DNA may be warranted in patients with persistent cytopenias. No patient treated with TREGZI has developed PTLD. Monitor for malignancies of donor origin and secondary malignancies. Contact Orca Bio at 1-877-290-6722 if any patient is diagnosed with a secondary malignancy or a malignancy of donor origin.

Transmission of Infectious Agents: Transmission of serious infectious or communicable disease or agents may occur with TREGZI treatment as it is derived from human donor blood and manufactured using animal-derived reagents. Risks of transmission of infectious agents may occur despite screening or testing of donors. Risks of transmission of serious infections include, but are not limited to, human immunodeficiency virus, human T cell lymphotropic virus (HTLV)-1 and -2, hepatitis B virus (HBV), hepatitis C virus (HCV), Treponema pallidum, Trypanosoma cruzi, West Nile virus (WNV), cytomegalovirus, transmissible spongiform encephalopathy agents and vaccinia. Monitor patients for signs and symptoms of infections, perform tests for infectious agents and treat as clinically indicated.

ADVERSE REACTIONS

The most common adverse reactions (incidence ≥ 20%) were mucositis, diarrhea, rash, viral infections, infections – pathogen unspecified, abdominal pain, vomiting, nausea, bacterial infections, hemorrhage, aGVHD, edema, and fungal infections.

The most common Grade 3-4 laboratory abnormalities (≥ 20%) are lymphocyte count decreased, platelet count decreased, leukocyte count decreased, neutrophil count decreased and hemoglobin decreased.

INDICATIONS AND USAGE

TREGZI is indicated for use in matched donor hematopoietic stem cell transplantation with myeloablative preparative regimen, for hematopoietic and immunologic reconstitution and to improve chronic graft-versus-host disease-free survival, in the treatment of adults with hematological malignancies.

Please see accompanying full Prescribing Information.

References:

  1.  Meyer E, Salhotra A, Gandhi A, et al. Orca-T versus allogeneic hematopoietic stem cell transplantation (Precision-T): a multicenter, randomized phase 3 trial. Blood. 2026;147(11):1168-1177. doi:10.1182/blood.2025031313
  2. TREGZI™ (allogeneic regulatory T cell immunotherapy with HSPC and T cells-vldq). Prescribing information. Orca Biosystems, Inc; 2026.
  3. Meyer E, Salhotra A, Gandhi A, et al. Orca-T versus allogeneic hematopoietic stem cell transplantation (Precision-T): a multicenter, randomized phase 3 trial. Supplemental appendix. Blood. 2026;147:1168-1177. doi:10.1182/blood.2025031313
  4. Data on file. Orca Biosystems, Inc; 2026.