Senti Bio completes Type B RMAT meeting with FDA on SENTI-202

Senti Bio (SNTI) announced the successful completion of a Type B Initial Comprehensive Multidisciplinary Regenerative Medicine Advanced Therapy, or RMAT, meeting with the FDA regarding SENTI-202, the company’s Logic Gated off-the-shelf CAR-NK cell therapy for relapsed/refractory acute myeloid leukemia and updated Phase 1 clinical data. Following the RMAT meeting, the company has finalized its pivotal clinical and chemistry, manufacturing and controls strategy for SENTI-202. The company plans to implement a single-arm, multi-center pivotal trial intended to support potential SENTI-202 registration in patients with R/R AML. This study is expected to evaluate SENTI-202 administered following lymphodepletion chemotherapy in a patient population consistent with the Phase 1 trial population. In addition to the RMAT meeting, after conducting exploratory efficacy covariate analysis of the Phase 1 trial results, Senti has identified a specific Donor X attribute that correlates with efficacy of SENTI-202, with 50% of the patients achieving a cCR when they received any SENTI-202 doses manufactured from Donor X-characteristic-derived NK cells in Cycle 1 versus 12.5% achieving a cCR when they received SENTI-202 manufactured from non-Donor X NK cells. As a result of this discovery, all future SENTI-202 manufacturing, including for pivotal study use, will use Donor X material. The Donor X attribute is found in ~50% of adult donors, and published literature supports increased NK cell cytotoxicity in donors with this phenotype. The Donor X NK phenotype is independent of HLA or KIR matching, thus supporting SENTI-202’s allogeneic off-the-shelf usage. Retrospective analysis of preclinical MV4-11 NSG mouse model data confirmed increased activity and survival with Donor X product. Senti Bio also announced that SENTI-202 continues to exhibit durable MRD-negative responses in the full 22 patient Phase 1 trial, which compares favorably with current FDA approved therapies for R/R AML. At RP2D, across all patients receiving a mix of Donor X and non-Donor X material, an ORR of 44% and cCR of 37.5% was observed with 100% of CRs being MRD negative. The complete remissions continue to be durable, with all the CR/CRh responders who were in remission as of the data-cut supporting the oral presentation at the 2025 ASH annual meeting continuing to maintain remission with an additional 7 months of follow up, the longest duration being 21+ months.