FDA Grants Orphan Drug Designation to SENTI-202 for Relapsed or Refractory AML and MDS

SENTI-202 has received FDA Orphan Drug Designation for the treatment of relapsed or refractory hematologic malignancies such as acute myeloid leukemia (AML) and myelodysplastic syndromes.¹

SENTI-202 is a first-in-class, off-the-shelf, logic-gated chimeric antigen receptor natural killer (CAR-NK) cell therapy that targets CD33 or FLT3-expressing hematologic malignancies while sparing healthy bone marrow cells. It is being developed by Senti Biosciences, Inc under their Gene Circuit platform.¹

The agent is currently being evaluated in a dose-finding phase 1 study, which is utilizing a 3+3 study design to determine the maximum tolerated dose or recommended phase 2 dose of SENTI-202 following lymphodepleting chemotherapy.^1,2

In a study presented at the American Society of Clinical Oncology (ASCO) 2025 Annual Meeting, SENTI-202 provided “exceptional efficacy” against AML in a humanized mouse model while protecting hematopoietic stem and progenitor cells from off-tumor toxicity.³ Specifically, treatment with SENTI-202 increased the frequency of hematopoietic stem and progenitor cells compared with inhibitory CAR control NK cells (34.2% vs 18.15% of hCD45+; P=0.00000355).³

“SENTI-202 continues to demonstrate encouraging promise as a potential treatment option for relapsed/refractory AML, an indication with significant unmet need and a dismal median survival rate of 5.3 months,” said Timothy Lu, MD, PhD, Senti Biosciences co-founder and CEO, in a press release.¹ “Receiving Orphan Drug Designation for SENTI-202 provides further validation to our novel approach to overcoming AML heterogeneity and protecting healthy cells, and underscores the need for new and effective treatment options.”