SENTI-202: Off-the-shelf Logic Gated CAR NK Cell Therapy in Adults with CD33 And/or FLT3 Blood Cancers Including AML/MDS

Inclusion Criteria:

• Subjects with CD33 and/or FLT3 expressing malignancies, including:

• Relapsed refractory acute myeloid leukemia (AML) with morphologic relapse asdefined by ≥5% bone marrow blasts who have received at least 1 prior line, butno more than 3 prior lines of standard anti-AML therapy. Subjects withFLT3-mutated or IDH ½-mutated disease must have received at least one priortargeted therapy.

• Relapsed refractory myelodysplastic syndrome (MDS) with increased blasts whohave received at least 1 prior line, but no more than 2 prior lines of anti-MDStherapy

• Other hematological malignancies who have received at least 1 prior line ofstandard of care for the respective disease

• Documentation of CD33 expression (or FLT3 expression if available) byindividual institutional standard of care

• ECOG performance score of 0-1

• Adequate organ function including platelet count >20x109/L (platelet transfusion ispermitted)

• Adequate recovery from toxicities from previous cancer treatments, as described inthe study protocol

• Willing and able to provide written informed consent

Exclusion Criteria:

• White blood cell (WBC) count of ≥20×109/L or circulating blasts ≥10×109/L or rapidlyprogressive/hyperproliferative disease

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

• MDS with fibrosis (MDS-f) or known prior history of constitutionalconditions/syndromes with chemo-responsive AML

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

• Presence of extra-medullary disease or myeloid sarcoma alone with no morphologichematologic relapse

• Prior use of certain anti-cancer therapies and/or use within a certain number ofdays prior to SENTI-202 study treatment, as described in the study protocol

• Hematopoietic cell transplantation (HCT) less than 100 days prior to the first doseof SENTI-202

• Prior NK cell or CAR T cell therapy at any time

• Prior donor lymphocyte infusion (DLI), except if after HCT for MRD+ disease

• Medical conditions or medications prohibited by the study protocol

• Pregnant or breastfeeding female