Senti Bio reports positive initial clinical data from Phase 1 trial of SENTI-202

The company states: “Senti Bio (SNTI)science reported positive initial clinical data from a Phase 1 clinical trial of SENTI-202, a potential first-in-class Logic Gated off-the-shelf chimeric antigen receptor natural kille investigational cell therapy, for the treatment of relapsed/refractory hematologic malignancies including acute myeloid leukemia. SENTI-202 is designed to selectively target and eliminate CD33 and/or FLT3- expressing hematologic malignancies, including AML, while sparing healthy bone marrow cells. Three AML patients have been treated at the lowest dose level (1.0 billion CAR+ NK cells per dose) and, as of the data cutoff date of September 19, 2024, two achieved complete remission, confirmed by bone marrow biopsy, which includes blast reduction and recovery of blood cells to normal ranges. In addition, both patients were assessed as measurable residual disease negative after treatment, which is defined as no detectable cancer cells present in a bone marrow sample by the most sensitive locally available method. As of today, both patients continue to maintain their remission (4+ months and 3+ months, respectively). In all three patients, SENTI-202 was generally well-tolerated with an adverse event profile consistent with the use of lymphodepleting chemotherapy in patients with AML. As of the data cut, three patients with R/R AML were enrolled at the 1.0 billion CAR+ NK cells/dose level, administered three times, on days 0, 7, and 14 of a 28-day cycle following lymphodepletion with fludarabine/cytarabine. The lowest dose cohort was cleared by the Safety Review Committee and dose escalation is continuing at the 1.5 billion CAR+ NK cells/dose level. Two patients achieved CR; one after two cycles and the other after one cycle, both with absent MRD by the most sensitive methods available for the patients at the respective clinical sites. With an additional two months of follow-up since the data cut, both patients are continuing to maintain MRD negative CR status (4+ months and 3+ months, respectively). One patient had no response after one cycle of treatment and was refractory to therapy. SENTI-202 was generally well-tolerated with no dose limiting toxicities (“DLTs”) and an adverse event profile consistent with other investigational NK cell therapies and patients with underlying AML receiving lymphodepleting chemotherapy. SENTI-202 transgene was detected in the peripheral circulation of all 3 patients and in all cycles, with a pharmacokinetic (“PK”) profile generally consistent with other investigational CAR-NK therapy levels.”