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

Key Inclusion Criteria:

   1. Age ≥ 18 and ≤ 65 years at the time of enrollment

   2. Diagnosed acute myeloid, lymphoid or mixed phenotype leukemia, or high or very high
   risk myelodysplasic syndrome (MDS), myelofibrosis, or chronic myeloid leukemia

   3. Planned to undergo myeloablative allogeneic hematopoietic stem cell transplant (HCT)

   4. Matched to a 8/8 or 7/8 related or unrelated donor, or to a related haploidentical
   donor

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

   6. Cardiac ejection fraction at rest ≥ 45% or shortening fraction of ≥ 27% by
   echocardiogram or radionuclide scan (MUGA)

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

   8. Total bilirubin < 1.5 times upper limit of normal (ULN) (< 3 times if attributed to
   Gilbert's syndrome) and ALT/AST < 3 times ULN

Key Exclusion Criteria:

   1. Prior allogeneic HCT

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

   3. Planned donor lymphocyte infusion (DLI)

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

   5. Karnofsky performance score < 70% (Appendix 12.7)

   6. Hematopoietic cell transplantation-specific Comorbidity Index (HCT-CI) > 4 (Appendix
   12.8)

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

   8. Seropositive for HIV-1 or -2, HTLV-1 or -2

   9. Any uncontrolled autoimmune disease requiring active immunosuppressive treatment

10. Concurrent malignancies or active disease within 1 year, except non-melanoma skin
   cancers that have been curatively resected

11. History of idiopathic or secondary myelofibrosis

12. Women who are pregnant or breastfeeding