Senti Biosciences (SNTI) Study Update summary

Study background and rationale

• Senti 202/SENTI-202 is a first-in-class, off-the-shelf logic-gated CAR-NK cell therapy targeting CD33 or FLT3 with a NOT gate for endomucin, designed to selectively kill AML cells while sparing healthy cells.

• The therapy addresses the challenge of finding clean targets in AML by using logic gates to enhance selectivity and reduce toxicity.

• Senti 202 includes a calibrated release IL-15 to boost NK cell and host immune activity.

• The product is manufactured from healthy adult donor NK cells, enabling rapid, scalable, allogeneic, off-the-shelf delivery.

• The addressable market is broad, with potential expansion into newly diagnosed AML, pediatric AML, and myelodysplastic syndrome.

Clinical trial design and patient population

• Phase 1, open-label, multinational, multicenter trial enrolled 20 heavily pretreated relapsed/refractory AML or MDS patients, including those with adverse risk genetics and poor prognosis.

• Dose finding followed by expansion at the recommended phase 2 dose (RP2D) of 1.5 x 10⁹ CAR+ NK cells.

• Patients had a median of 2 prior lines of therapy, with high rates of prior HCT and refractory disease.

• Median age was 49, with most patients having received multiple prior lines of therapy, including chemotherapy and targeted agents.

• The RP2D cohort had more heavily pretreated and refractory patients compared to dose level one.

Efficacy results

• 50% overall response rate (ORR) and 42% CR/CRh rate at RP2D in relapsed/refractory AML patients.

• All complete remissions (CR) were MRD negative, with MRD negativity rates exceeding 80% across all response types.

• Responses were rapid (median time to response 1.2 months) and durable, with estimated median duration of composite CR at 7.6 months; some responses lasted over a year.

• Responses observed across diverse patient subgroups, including those with adverse risk genetics and prior refractory disease.

• Efficacy was independent of FLT3 mutation status, benefiting both wild-type and mutant patients.