Senti Biosciences, Inc. announced the acceptance of three abstracts for presentation at the American Association for Cancer Research (AACR) Annual Meeting being held April 14-19, 2023, in Orlando, Florida. Senti Bio is using gene circuits to create next-generation cell and gene therapies and is advancing a pipeline of gene circuit-enabled chimeric antigen receptor natural killer (CAR-NK) cell therapies. 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, Authors: Alba Gonzalez, Gozde Yucel, Enping Hong, Elizabeth Leitner, Pearley Chinta, Han Deng, Ian Li, Alice Lam, Abla Bakir, Brandon Lee, Papia Chakraborty, Carmina Blanco, Kelly Lee, Niran Almudhfar, Mengxi Tian, Wenqi Song, Andrew Banicki, Otto Contreras, Marty Gieldin, Brian Garrison, Timothy Lu, Kanya Rajangam, Date and Time: April 17, 20231:30 PM - 5:00 PM, Session Name: Adoptive Cell Therapy 2, Abstract Number: 3195.

Preclinical data will be presented describing the efficacy and safety profile of SENTI-202, a first-in-class logic gated (OR+NOT) off-the-shelf CAR-NK cell therapy designed to selectively target and eliminate CD33 and/or FLT3 expressing hematologic malignancies like acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) while sparing the healthy bone marrow. SENTI-202 is also multi-armed with a calibrated release IL-15 (crIL-15) gene circuit to provide NK cell activation and persistence. These data support the clinical development of SENTI-202 as a novel therapeutic option for patients with CD33+ and/or FLT3+ tumors.

Senti Bio plans to file an Investigational New Drug (IND) Application for SENTI-202 in the second half of 2023. Title: Off-the-Shelf CAR-NK cells engineered to express calibrated release IL-15 exhibit enhanced persistence and anti-tumor activities, Authors:Chen-Ting Lee, Michelle Hung, Andrew Banicki, Wenqi Song, Niran Almudhfar, Deepika Kaveri, Priscilla Wong, Lawrence Naitmazi, Marcela Guzman, Alice Lam, Gozde Yucel, Timothy Lu, Alba Gonzalez Junca, Brian Garrison and Philip Lee, Date and Time: April 17, 20231:30 PM - 5:00 PM, Session Name: Natural Killer and Natural Killer T Cell-based Cellular Therapies, Abstract Number: 2902. Preclinical data will be presented demonstrating that multi-armed NK cells engineered to co-express a CAR and a calibrated release (cr) IL-15 can improve persistence and anti-tumor activity of CAR-NK cells.

The crIL-15 gene circuit is incorporated into all current internal pipeline products including SENTI-202 being developed for CD33 and/or FLT3 expressing hematologic malignancies including AML and MDS, SENTI-401 being developed for CEA expressing tumors including colorectal cancer and other solid tumors, and SENTI-301A for GPC3 expressing tumors including hepatocellular carcinoma. Title: SENTI-301A, an off-the-shelf multi-armed preclinical CAR-NK cell therapy, for the treatment of GPC3 expressing tumors, Authors:Deepika Kaveri, Enping Hong, Elizabeth Leitner, Priscilla Wong, Ronni Ponek, Lawrence Naitmazi, Pearley Chinta, Wesley Gorman, Mengxi Tian, Niran Almudhfar, Kelly Lee, Nicholas Frankel, Russell Gordley, Philip Lee, Alba Gonzalez Junca, Timothy Lu, Kanya Rajangam, Marcela Guzman Ayala, Date and Time: April 17, 20231:30 PM - 5:00 PM, Session Name: Natural Killer and Natural Killer T Cell-based Cellular Therapies, Abstract Number: 2905. Preclinical data will be presented from SENTI-301A, an off-the-shelf CAR-NK product candidate engineered with a GPC3 CAR and calibrated-release interleukin-15 (crIL-15) targeting GPC3 expressing solid tumors such as hepatocellular carcinomas (HCC).

Senti Bio is pursuing strategic geographic partnerships for SENTI-301A to enable clinical development in areas with high HCC incidence such as in China.