NKX101, Intravenous Allogeneic CAR NK Cells, in Adults With AML or MDS

Inclusion Criteria:

• General:

• ECOG performance status ≤2

• Disease related:

• For AML subjects:

• Previously treated relapsed/refractory AML, including subjects with MRD+disease

• Received at most 3 lines of previous anti-leukemia therapy

• For subjects with targetable fms-like tyrosine kinase 3 (FLT3)-mutated orisocitrate dehydrogenase (IDH)1/2 mutated disease, subjects must havereceived at least 1 prior respective targeted therapy and may receive upto 4 lines of prior therapy

• White blood cell count of ≤25 × 10^9/L

• For groups receiving NKX101 after lymphodepletion withfludarabine/cyclophosphamide +/- decitabine: Disease localized to the bonemarrow, as evidenced by ≤ 5% peripheral blasts and no evidence ofextramedullary disease

• For groups receiving NKX101 after lymphodepletion with fludarabine/cyclophosphamide +/- decitabine, group receiving NKX101 afterlymphodepletion with fludarabine/ara-C: Additional subjects withspecifically high-risk genetic mutations may be enrolled. High riskgenetic mutation per ELN 2022 should be evaluated as per local assay anddiscussed with the Sponsor prior to study entry

• For groups receiving NKX101 after lymphodepletion withfludarabine/cyclophosphamide +/- decitabine, group receiving NKX101 afterlymphodepletion with fludarabine/ara-C: Additional subjects who haverelapsed following HCT may be enrolled.

• For MDS subjects:

• Intermediate-, high-, or very high-risk MDS

• Previously treated relapsed/refractory MDS

• Received at least 1 and at most 3 lines of previous standard anti-MDStherapy

• For groups receiving NKX101 after lymphodepletion with fludarabine/cyclophosphamide +/- decitabine: Additional subjects with specificallyhigh-risk disease may be enrolled. High-risk genetic mutation should beevaluated as per local assay

• For group receiving lymphodepletion with fludarabine/cyclophosphamide +/-decitabine and NKX101: Additional subjects who have relapsed following HCTmay be enrolled.

• Adequate Organ Function

• Platelet count ≥30,000/uL (platelet transfusions acceptable)

• Other:

• Signed informed consent

• Agree to use an effective barrier method of birth control

Exclusion Criteria:

• Disease related:

• Acute promyelocytic leukemia with t(15;17) (q22;q12); or abnormal promyelocyticleukemia/retinoic acid receptor alpha (APML-RARA) and AML arising from chronicmyelomonocytic leukemia (CMML)

• Evidence of leukemic meningitis or known active central nervous system disease

• Peripheral leukocytosis with ≥ 20,000 blasts/μL or other evidence of rapidlyprogressive disease that would preclude subject from completing at least 1cycle of treatment

• Use of any anti-AML/MDS chemotherapeutic or targeted small molecule drug withinprotocol specified window prior to the first dose of NKX101

• Presence of residual non-hematologic toxicity from prior therapies that has notresolved to ≤ Grade 1

• Any hematopoietic cell transplantation within 16 weeks

• Other comorbid conditions and concomitant medications prohibited as per studyprotocol

• Other:

• Pregnant or lactating female