NEW YORK – Senti Biosciences on Monday said it will use an $8 million grant from the California Institute for Regenerative Medicine to further develop its off-the-shelf chimeric antigen receptor natural killer (CAR-NK) cell therapy SENTI-202 in CD33- or FLT3-expressing hematologic malignancies.
Senti Bio researchers are currently studying the cell therapy in a Phase I trial, into which they hope to enroll about 21 patients with relapsed or refractory CD33- or FLT3-expressing hematologic malignancies, including acute myeloid leukemia and myelodysplastic syndrome. In the first part of the study, the investigators will determine a recommended Phase II dose for SENTI-202. Then in the second part of the trial, they will enroll other disease-specific cohorts to explore the safety, biodynamics, and anti-cancer activity of SENTI-202.
Senti Bio developed SENTI-202 using its Gene Circuits synthetic biology platform. SENTI-202 comprises three parts: a CAR that targets CD33 and FLT3; an inhibitor CAR that protects healthy cells from on- or off-target toxicity; and a component that releases IL-15 to increase cell persistence, expansion, and activity.
In a preclinical study, Senti Bio's CAR-NK cells recognized and killed FLT3- and CD33-expressing AML cells but protected healthy hematopoietic stem cells (HSCs) through inhibitory CAR recognition of endomucin, which is expressed only on healthy HSCs. In a mouse model, the CAR-NKs also killed multiple AML subtypes while protecting healthy HSCs.
The South San Francisco, California-based firm expects to report initial efficacy data from this Phase I trial by the end of the year and treatment durability results in 2025.