FDA Grants RMAT Designation to Senti Bio’s Logic-Gated CAR-NK Therapy for AML

SOUTH SAN FRANCISCO, Calif. — December 9, 2025

Senti Biosciences, Inc. (Nasdaq: SNTI) announced today that the U.S. Food and Drug Administration (FDA) has granted Regenerative Medicine Advanced Therapy (RMAT) designation to SENTI-202. This investigational, potential first-in-class “off-the-shelf” chimeric antigen receptor natural killer (CAR-NK) cell therapy is currently being evaluated for the treatment of relapsed/refractory (R/R) acute myeloid leukemia (AML) and other hematologic malignancies.

The RMAT designation is designed to expedite the development and review of regenerative medicines that show early clinical evidence of addressing significant unmet medical needs. This marks the second major regulatory milestone for SENTI-202 this year, following the receipt of Orphan Drug Designation in June 2025.

Breakthrough Clinical Data at ASH 2025

The FDA’s decision was bolstered by clinical data presented at the American Society of Hematology (ASH) Annual Meeting on December 8. The updated results from the ongoing Phase 1 trial demonstrated:

• An Overall Response Rate (ORR) of 50% and a Complete Remission (CR/CRh) rate of 42% at the Recommended Phase 2 Dose (RP2D).

• A 7.6-month median duration of composite Complete Remission across the patient cohort.

• A well-tolerated safety profile with evidence of deep and durable responses in a notoriously aggressive cancer.

The “Logic Gate” Advantage

SENTI-202 is built upon Senti Bio’s proprietary Gene Circuit platform, utilizing a sophisticated “OR/NOT” Logic Gate system to solve a central challenge in oncology: killing cancer while sparing healthy tissue.

1. OR Gate: This activating component allows the CAR-NK cells to recognize and kill cells expressing CD33 and/or FLT3. This dual-targeting is designed to eliminate both leukemic blasts and the leukemic stem cells that often cause relapse.

2. NOT Gate: This inhibitory component is designed to recognize EMCN, a marker selectively expressed on healthy hematopoietic stem cells. If the CAR-NK cell encounters a healthy cell, the NOT gate overrides the kill signal, protecting the patient’s healthy bone marrow even if it expresses CD33 or FLT3.

3. Calibrated-release IL-15: This integrated cytokine is designed to enhance the persistence and activity of the NK cells within the body.

“This significant FDA designation validates the promise of SENTI-202 to transform the therapeutic landscape for R/R AML,” said Timothy Lu, MD, PhD, Co-Founder and CEO of Senti Biosciences. “We are incredibly pleased with the clinical proof-of-mechanism for our Logic Gate technology, which shows selective killing of leukemic cells while sparing healthy progenitor cells.”

The RMAT status will allow Senti Bio to work closely with the FDA, receiving intensive guidance on efficient data generation to support a potential future approval. The company is currently continuing enrollment for its Phase 1 trial (NCT06325748).