Precision-T: A Study of Orca-T in Recipients Undergoing Allogeneic Transplantation for Hematologic Malignancies

Key Inclusion Criteria:

Recipients must meet all of the following criteria:

1. Patients must diagnosed with one of the following histopathologically confirmeddiseases, for which a myeloablative hematopoietic stem cell transplant (HCT) isplanned: A) Acute myeloid, lymphoid, or mixed phenotype/undifferentiated leukemia who are notin CR or CRi (active disease) and/or MDS with >10% to <20% bone marrow blast burden (ages 18 to 75 years) B) Acute leukemia in CR/CRi or MDS that is DRI intermediate to high risk (ages 66 to 75 years) C) BPDCN (ages 18 to 65 years) D) Participants aged 18 to 65 who would be eligible for the Phase 3 component ofPrecision-T except for mild impairments of renal and/or hepatic function as definedby an eGFR of 50 to <60 mL/min and/or a total bilirubin of >ULN to ≤2 x ULN anddiagnosed with either of the following: i. Acute myeloid, lymphoid, or mixed phenotype/undifferentiated leukemia that is inCR/CRi and DRI intermediate to high risk a) MDS that is DRI intermediate to high risk E) Acute or chronic leukemia in remission that is DRI low risk (ages 18 to 65years), including the following: i. CML in chronic phase but with a history of accelerated phase or blast crisis orwho are resistant to or intolerant of more than 1 first- and second-generationtyrosine kinase inhibitors ii. Acute myeloid leukemia (AML) with inv(16) without accompanying complexcytogenetics

2. Patients must be matched to a 8/8 HLA-matched related or unrelated donor

3. Estimated glomerular filtration rate (eGFR) > 50 mL/minute

4. Cardiac ejection fraction at rest ≥ 45% or shortening fraction of ≥ 27% byechocardiogram or radionuclide scan (MUGA)

5. Diffusing capacity of the lung for carbon monoxide (DLCO) (adjusted for hemoglobin) ≥ 50%

6. Total bilirubin < 2 times upper limit of normal (ULN) (patients with Gilbert'ssyndrome may be included where hemolysis has been excluded) and ALT/AST < 3 timesULN

Key Exclusion Criteria:

Recipients meeting any of the following exclusion criteria will not be eligible:

1. History of prior allogeneic HCT

2. Currently receiving corticosteroids or other immunosuppressive therapy. Topicalcorticosteroids or oral systemic corticosteroid doses less than or equal to 10mg/day are allowed.

3. Pre-planned donor lymphocyte infusion (DLI)

4. Planned pharmaceutical in vivo or ex vivo T cell depletion

5. Positive for anti-donor HLA antibodies against an allele in the selected donor

6. Karnofsky performance score < 70%

7. Hematopoietic cell transplantation-specific Comorbidity Index (HCT-CI) > 4

8. Uncontrolled bacterial, viral or fungal infections (currently taking antimicrobialtherapy and with progression or no clinical improvement) at time of enrollment

9. Seropositive for HIV-1 or -2 antibody, HTLV-1 or -2 antibody, Hepatitis B sAg, orHepatitis C antibody

10. Any uncontrolled autoimmune disease requiring active immunosuppressive treatment

11. Concurrent malignancies or active disease within 1 year, except non-melanoma skincancers that have been curatively resected

12. Women who are pregnant or breastfeeding