Senti Bio highlights preclinical data from cell therapy programs at AACR meeting

Senti Biosciences announced the presentation of preclinical data from multiple wholly-owned pipeline programs at the American Association for Cancer Research Annual Meeting being held April 14-19, 2023, in Orlando, Florida. Senti Bio is advancing a pipeline of gene circuit-enabled chimeric antigen receptor natural killer cell therapies for the treatment of liquid and solid tumors. Presentation Title: Preclinical development of SENTI-202, an off-the-shelf logic gated CAR-NK cell therapy, for the treatment of CD33/FLT3+ hematologic malignancies including AML: SENTI-202 CAR-NK cells, which include a CD33 and/or FLT3 targeting activating CAR, showed increased cytotoxic activity, serial killing, and cytokine production compared to unengineered NK cells within in vitro and in vivo AML models, as well as killing of primary tumor-derived samples from AML and MDS patients. SENTI-202, which has the endomucin inhibitory CAR as part of its gene circuit, preferentially protected healthy hematopoietic cells compared to CAR-NK cells without the iCAR. The colony-forming potential of hematopoietic stem and progenitor cells was preserved after exposure to SENTI-202. SENTI-202, which expressescrIL-15, showed increased persistence compared to unengineered NK cells. Senti Bio remains on track to file an Investigational New Drug application for SENTI-202 in patients with CD33 and/or FLT3 expressing hematologic malignancies in the second half of 2023 with the planned Phase 1 trial focusing on relapsed/refractory patients including AML. Presentation Title: Off-the-Shelf CAR-NK cells engineered to express crIL-15 exhibit enhanced persistence and anti-tumor activity: Inclusion of crIL15 to gene circuits resulted in enhanced NK cell persistence and tumor killing activity in CAR-NK cells as well as activation of neighboring T cells and NK cells. Additionally, wide biodistribution and prolonged persistence of NK cells engineered with crIL-15 were observed. Importantly, in AML xenograft models, data showed CAR-NK cells engineered with crIL-15 technology significantly reduced tumor burden and prolonged mouse survival compared to unengineered NK cells. These data demonstrate that NK cells engineered to co-express CAR and crIL-15 can improve persistence and anti-tumor activity of CAR-NK cells. Presentation Title: SENTI-301A, an off-the-shelf multi-armed preclinical CAR-NK cell therapy for the treatment of GPC3 expressing tumors: SENTI-301A demonstrated CAR-driven killing and antigen specificity against target cell lines, and showed significantly higher in vitro cytotoxic activity against both HCC and non-HCC GPC3-expressing cell lines. SENTI-301A exhibited increased crIL-15-driven persistence and cytotoxicity compared to unengineered NK cells. SENTI-301A demonstrated tumor infiltration and enhanced persistence, antitumor function, and increased median survival compared to unengineered NK cells in HCC xenograft models.