Senti Bio Reports Positive Preliminary Phase 1 Data for Logic Gated CAR-NK Therapy SENTI-202 in Relapsed/Refractory AML

SOUTH SAN FRANCISCO, Calif., April 28, 2025 (GLOBE NEWSWIRE) — Senti Biosciences, Inc. (Nasdaq: SNTI) (“Senti Bio”), a clinical-stage biotechnology company developing next-generation cell and gene therapies using its proprietary Gene Circuit platform, today announced additional positive preliminary data from its Phase 1 clinical trial of SENTI-202. SENTI-202 is a potential first-in-class off-the-shelf Logic Gated selective CD33 OR FLT3 NOT EMCN chimeric antigen receptor natural killer (CAR-NK) investigational cell therapy for relapsed/refractory (R/R) hematologic malignancies, including acute myeloid leukemia (AML). The Company hosted a conference call and webcast today to discuss these data.

SENTI-202 Clinical Data Update

The positive preliminary SENTI-202 clinical data was presented on April 27 at the American Association for Cancer Research (AACR) Annual Meeting 2025 in a Clinical Trials Oral Minisymposium, abstract titled, “First-in-human, multicenter study of SENTI-202, a CD33/FLT3 selective off-the-shelf logic gated CAR NK cell therapy in hematologic malignancies including AML: Clinical data.”

Timothy Lu, MD, PhD, Co-Founder and CEO of Senti Biosciences, commented, “Senti Bio was founded on engineering Logic Gated cell therapies with the enhanced ability to selectively kill cancer cells and protect healthy cells for cancer indications not addressable by existing drugs. We are continuing to prioritize development of our Logic Gating programs, including SENTI-202 and additional discovery efforts for solid tumors, based on these exciting results.”

SENTI-202 Clinical Results Summary

As presented at AACR, 9 patients with relapsed or refractory AML have been treated with SENTI-202 at various doses in the dose-finding portion of the study, with 7 evaluable for overall response at the data cut-off.

The Phase 1 study evaluated two dose levels (1 or 1.5 x 10^9 CAR NK cells/dose) and two schedules (3 or 5 doses) of SENTI-202 administered every 28 days on Days 0, 7, 14 or Days 0, 3, 7, 10, 14, respectively, following lymphodepletion with fludarabine/Ara-C.

SENTI-202 was well-tolerated, with no dose-limiting toxicities observed, and a maximum tolerated dose was not reached. The preliminary recommended Phase 2 dose (RP2D) was identified as 1.5 x 10^9 CAR NK cells administered on Days 0, 7, 14 in 28-day Cycles following lymphodepleting chemotherapy, based on the totality of clinical data including efficacy.

Efficacy

• 2 of 3 patients in the preliminary RP2D cohort achieved a composite Complete Remission (cCR).
• 5 of the 7 best overall response evaluable patients achieved an ORR (cCR + morphologic leukemia-free state), and 4 of the 7 achieved cCR (3 CR with full hematologic recovery, and 1 CRh (CR with partial hematologic recovery)).
• 4 of 4 cCR patients were MRD- (Measurable Residual Disease Negative) as assessed by local standard of care.
• All cCR patients continue in remission, with the longest follow-up being 8+ months, and 3 patients received a bone marrow transplant after treatment with SENTI-202.

Pharmacokinetics (PK) SENTI-202 was detected in all treated patients, consistent with other allogeneic CAR NK cell therapy PK profiles, showing modest expansion in the first 14 days in the periphery followed by clearance from peripheral blood.

Bone marrow Cytometry by Time of Flight (CyTOF) analyses SENTI-202 treatment decreased AML blasts and leukemia stem cell (LSC) frequencies and maintained (or increased) healthy hematopoietic stem and progenitor cell (HSPC) frequencies in patients achieving cCR, consistent with the designed mechanism of action of the SENTI-202 Logic Gated gene circuit.

Safety SENTI-202 is generally well tolerated, with an adverse event profile consistent with other investigational NK cell therapies and patients with underlying AML receiving lymphodepleting chemotherapy. Grade 3 or higher events reported in >1 patient included febrile neutropenia and decreased platelet count (four patients each), and anemia and abdominal pain (two patients each). These side effects were deemed unrelated to SENTI-202 or resulting from lymphodepleting chemotherapy in all patients except one. No grade 5 adverse events were observed.

The Phase 1 study of SENTI-202 is continuing to enroll to confirm the preliminary RP2D, followed by disease-specific expansion cohorts. The trial is partly funded by a grant from the California Institute for Regenerative Medicine.

Kanya Rajangam, MD, PhD, President, Head of R&D and Chief Medical Officer of Senti Bio, summarized, “Based on our clinical, correlative, and preclinical data, we believe SENTI-202 has the potential to provide a safe and effective treatment option for AML. We remain focused on the successful execution of the study and look forward to further exploring SENTI-202’s potential.”

Stephen A. Strickland, Jr., MD, MSCI, Director, Leukemia Research for Sarah Cannon Research Institute, and the lead author for the AACR abstract, added, “While preliminary, the results demonstrated by SENTI-202 to date continue to be encouraging. There remains a significant unmet medical need in AML for treatments that can overcome tumor heterogeneity and spare healthy cells. Early results are encouraging, not only for the deep, durable complete remissions, but also for the excellent safety profile noted thus far. I look forward to seeing additional data and exploring the potential of SENTI-202 to provide a much-needed treatment option to people living with AML.”