FDA Grants Orphan Drug Designation to SENTI-202 for R/R AML

US FDA

• The FDA has granted orphan drug designation (ODD) to SENTI-202 for relapsed/refractory (R/R) hematologic malignancies, including acute myeloid leukemia (AML).
• SENTI-202 is a first-in-class, off-the-shelf, logic-gated CAR NK-cell therapy engineered to selectively target CD33/FLT3+ malignant cells while sparing healthy bone marrow.
• A phase 1 trial (NCT06325748) is actively enrolling to evaluate safety, dose, and preliminary efficacy in adults with R/R AML, myelodysplastic syndrome (MDS), or other hematologic malignancies.

The FDA has granted orphan drug designation to SENTI-202, a first-in-class, off-the-shelf, CAR natural killer (NK)-cell therapy, for the treatment of patients with R/R hematologic malignancies, including AML.¹

Developed by Senti Biosciences, SENTI-202 is a synthetic biology-engineered NK-cell product designed to selectively target and eliminate malignant cells expressing CD33 and/or FLT3 while sparing healthy bone marrow. This design aims to address the heterogeneity of AML and improve therapeutic selectivity.

SENTI-202 is currently being evaluated in an ongoing phase 1 clinical trial.This open-label, multicenter study is assessing the safety, biodynamics, and preliminary antitumor activity of SENTI-202 in adult patients with R/R hematologic malignancies that express CD33 and/or FLT3, such as AML and MDS.

Acute myeloid leukemia (AML) cells in blood flow: © LASZLO - stock.adobe.com

"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. 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. Building upon our recently reported positive preliminary results, this important milestone bolsters our commitment to advancing the development of this important program forward," said Timothy Lu, MD, PhD, co-founder and chief executive officer of Senti Biosciences, in a press release.

The trial is divided into 2 parts. The first is a dose-escalation phase utilizing a modified 3+3 design to establish the maximum tolerated dose (MTD) and/or the recommended phase 2 dose (RP2D) following lymphodepleting chemotherapy with fludarabine and cytarabine. The second phase involves disease-specific expansion cohorts to further evaluate the therapy's safety and activity at the RP2D.²

Eligible patients must be between 18 and 74 years of age with morphologic relapse of AML (≥5% bone marrow blasts) after 1 to 3 prior lines of standard therapy. Those with FLT3- or IDH1/2-mutated disease are required to have received at least 1 targeted agent. Patients with MDS and increased blasts must have failed 1 or 2 prior regimens. The study also permits enrollment of patients with other R/R hematologic malignancies, provided they have received at least 1 prior standard-of-care therapy.

Additional eligibility requirements include documented CD33 expression or FLT3 expression (if available), an ECOG performance status of 0 or 1, and adequate organ function. Patients must have recovered from prior treatment-related toxicities and be capable of providing written informed consent.

SENTI-202 is being administered in 2 potential dosing regimens following lymphodepletion: a 3-dose schedule given on days 0, 7, and 14, and a 5-dose schedule on days 0, 3, 7, 10, and 14. The primary end point of the study is safety, with secondary end points assessing antitumor activity, pharmacokinetics, and immune response.

REFERENCES:

1. Senti Bio granted U.S. FDA orphan drug designation for use of first-in-class off-the-shelf logic gated selective CD33 or FLT3 not EMCN CAR NK cell therapy, SENTI-202, to treat acute myeloid leukemia. Senti Biosciences, Inc. June 18, 2025. Accessed June 18, 2025. https://tinyurl.com/mtt5wtmu

2. SENTI-202: Off-the-shelf logic gated CAR NK cell therapy in adults with CD33 and/or FLT3 blood cancers including AML/MDS. ClinicalTrials.gov. Updated March 30, 2025. Accessed June 18, 2025. https://clinicaltrials.gov/study/NCT06325748