AACR 2025 – Senti fails to impress

First the good news for Senti Biosciences: it reckons it's nailed down the ideal dose and schedule for its lead Car-NK therapy, SENTI-202. But the bad news is that investors weren’t convinced by a phase 1 update in relapsed/refractory, CD33/FLT3-expressing AML, presented at AACR on Monday. Last December Senti reported two complete responses among three patients receiving 1 billion SENTI-202 cells per dose in the same study. Now it has seen five responses (only three complete) among seven patients getting 1 and 1.5 billion SENTI-202 cells; the latter is the “preliminary” go-forward dose. As for safety, 44% of patients experienced grade 3 or higher febrile neutropenias and platelet count decreases; Senti blamed lymphodepletion, although one patient had grade 3 neutropenia and grade 4 platelet count decrease deemed possibly SENTI-202-related. In the December update all three patients developed grade 4 haematologic toxicity. The phase 1 trial will continue to enrol patients to confirm the go-forward dose, but some investors are already heading for the exit: the group’s stock closed down 27% on Monday, and another 13% on Tuesday. SENTI-202 uses an “or-gated” construct that targets either CD33 or FLT3. Other recent Car-NK disappointments have come from Century Therapeutics and Caribou.

Evolving data from ph1 SENTI-202-101 trial in r/r AML

Note: CRh=complete response with partial haematologic recovery. Source: AACR 2025 & company releases.