A Phase 1 Study of Orca-Q in Recipients Undergoing Allogeneic Transplantation for Hematologic Malignancies

Key Inclusion Criteria:

1. Age at the time of enrollment:

2. For MAC with fully matched donor (Arm A with 8/8 donor and Arm C) and NMA/RIC:Age ≥ 12 and ≤ 78 years

3. For MAC with mismatched donors (Arm A with 7/8 donor and Arm B): Age ≥ 12 and ≤ 65 years

4. Diagnosed acute myeloid, lymphoblastic or mixed phenotype leukemia, or high or veryhigh risk myelodysplastic syndrome (MDS) either in complete remission (CR) or with ≤ 10 percent of blast cells in bone marrow (BM)

5. Indicated for allogeneic hematopoietic stem cell transplant (alloHCT)

6. Matched to a 8/8 or 7/8 related or unrelated donor, or to a related haploidenticaldonor

7. Estimated glomerular filtration rate (eGFR) > 50 mL/minute (MAC with tacrolimus) or > 30 mL/minute (NMA/RIC or MAC without tacrolimus)

8. Cardiac parameters: Cardiac ejection fraction ≥ 45 percent (MAC) or ≥ 40 percent (NMA/RIC)

9. Diffusing capacity of the lung for carbon monoxide (DLCO) (adjusted for hemoglobin) ≥ 50 percent for MAC or ≥ 40 percent for NMA/RIC

10. Liver function: Total bilirubin < 1.5 times upper limit of normal (ULN) (MAC) or < 3times ULN (NMA/RIC); alanine transaminase (ALT)/aspartate transaminase (AST) < 3times ULN (MAC) or < 5 times ULN (NMA/RIC)

11. Participants enrolling on NMA/RIC-alloHCT arms must be deemed unfit for amyeloablative alloHCT per assessment of the principal investigator (PI)

Key Exclusion Criteria:

1. Prior alloHCT

2. Currently receiving corticosteroids or other immunosuppressive therapy except forapproved disease-specific therapy for the patient's underlying hematologicmalignancy. Topical corticosteroids or oral systemic corticosteroid doses less thanor equal to 10 mg/day are allowed

3. Planned donor lymphocyte infusion (DLI)

4. Planned pharmaceutical in vivo or ex vivo T cell depletion, e.g., post-transplantcyclophosphamide (Cy) or alemtuzumab

5. Positive anti-donor HLA antibodies against a mismatched allele in the selected donor

6. Low performance score: For MAC: Karnofsky Performance Score (KPS) < 70 percent, ForNMA/RIC: <60 percent

7. High HCT-specific Comorbidity Index (HCT-CI): For MAC > 4, For NMA/RIC >6

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

9. Seropositive for human immunodeficiency virus (HIV)-1 or -2, human T-lymphotropicvirus (HTLV)-1 or -2 or Hepatitis B surface antigen (HbsAg) or anti-Hepatitis Cvirus (HCV) antibody (Ab)

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. Patients with concurrent indolenthematologic malignancies that do not require active treatment and are under activesurveillance only (such as CLL, low-grade lymphomas, smoldering MM, MZL) may beincluded with the approval of Medical Monitor

12. History of idiopathic or secondary myelofibrosis

13. Women who are pregnant or breastfeeding