Senti Biosciences, Inc. (Nasdaq: SNTI) has reported encouraging preliminary clinical data from its Phase 1 trial of SENTI-202, a novel cell therapy designed to selectively target acute myeloid leukemia (AML) while sparing healthy cells. The data, presented at the American Association for Cancer Research (AACR) Annual Meeting 2025 in Chicago, demonstrates promising efficacy and safety in patients with relapsed or refractory hematologic malignancies.
Promising Clinical Responses in Difficult-to-Treat AML
In the dose-finding portion of the Phase 1 study, 9 patients with relapsed or refractory AML received SENTI-202, with 7 evaluable for response at the data cutoff. Five of these 7 patients (71%) achieved objective responses, including 3 complete remissions (CR), 1 CR with partial hematologic recovery (CRh), and 1 morphologic leukemia-free state.
Notably, all 4 patients who achieved composite complete remissions (cCR) were measurable residual disease (MRD) negative as assessed by local standard of care testing. These responses have proven durable, with all complete remissions ongoing at the time of data cutoff and the longest response extending beyond 8 months.
"While preliminary, the results demonstrated by SENTI-202 to date continue to be encouraging," said Dr. Stephen A. Strickland, Jr., Director of Leukemia Research for Sarah Cannon Research Institute and lead author of the AACR abstract. "There remains a significant unmet medical need in AML for treatments that can overcome tumor heterogeneity and spare healthy cells. Early results are encouraging, not only for the deep durable complete remissions, but also for the excellent safety profile noted thus far."
Innovative Gene Circuit Technology
SENTI-202 represents a novel approach to cell therapy, utilizing Senti Bio's proprietary Gene Circuit platform. The therapy incorporates three key components:
- An "OR GATE" with activating CARs targeting CD33 and/or FLT3, designed to kill both leukemic blasts and leukemia stem cells
- A "NOT GATE" with an inhibitory CAR recognizing EMCN (endomucin), designed to protect healthy hematopoietic stem and progenitor cells
- Calibrated-release IL-15 to enhance cell persistence and activity
This logic-gated approach aims to address a fundamental challenge in AML treatment: targeting cancer cells while sparing healthy bone marrow cells that share common markers. Correlative analyses presented at AACR showed that SENTI-202 treatment decreased AML blasts and leukemia stem cell frequencies while maintaining or increasing healthy hematopoietic stem and progenitor cell frequencies in patients achieving complete remissions.
Safety Profile and Dosing
The therapy demonstrated a favorable safety profile with no dose-limiting toxicities observed across the dose levels tested. The maximum tolerated dose was not reached, and the preliminary recommended Phase 2 dose was identified as 1.5 x 10^9 CAR-NK cells administered on days 0, 7, and 14 in 28-day cycles following lymphodepleting chemotherapy.
Adverse events were consistent with those expected for patients with underlying AML receiving lymphodepleting chemotherapy and other investigational NK cell therapies. Grade 3 or higher events reported in more than one patient included febrile neutropenia, decreased platelet count, anemia, and abdominal pain, but these were either deemed unrelated to SENTI-202 or attributed to lymphodepleting chemotherapy in all but one patient.
Expanding Clinical Program
Senti Bio is continuing to enroll patients in the Phase 1 study to confirm the preliminary recommended Phase 2 dose, with plans to advance to disease-specific expansion cohorts. The trial is partially funded by a grant from the California Institute for Regenerative Medicine.
"Senti was founded on engineering Logic Gated cell therapies with the enhanced ability to selectively kill cancer cells and protect healthy cells for cancer indications not addressable by existing drugs," said Dr. Timothy Lu, Co-Founder and CEO of Senti Biosciences. "Building upon these exciting results, we are continuing to prioritize development of our Logic Gating programs, including SENTI-202 and additional discovery efforts for solid tumors."
Additional Data Presentations
In addition to the oral presentation, Senti Bio is showcasing additional data on SENTI-202 in two poster presentations at AACR:
- Correlative data from the Phase 1 clinical trial, presented on April 29
- Preclinical findings demonstrating that SENTI-202's logic-gated components selectively target AML while protecting human hematopoietic stem and progenitor cells from off-tumor toxicity in a humanized mouse model, presented on April 30
Financial Position
Senti Bio also announced preliminary financial results for the first quarter of 2025, reporting cash and cash equivalents of approximately $33.8 million as of March 31, 2025. Research and development expenses were $9.3 million, up slightly from $8.8 million in the same period of 2024, while general and administrative expenses decreased to $7.1 million from $7.5 million. The company reported a net loss of $14.1 million, or $1.41 per basic and diluted share, for the quarter.
Addressing a Significant Unmet Need
AML is the most common type of acute leukemia in adults, with an estimated 20,800 new cases in the United States in 2024. The five-year survival rate is approximately 30%, and for patients with relapsed or refractory disease, median overall survival is typically around five months.
Dr. Kanya Rajangam, President, Head of R&D and Chief Medical Officer of Senti Bio, summarized the potential impact: "Based on our clinical, correlative and preclinical data, we believe SENTI-202 has the potential to provide a safe and effective treatment option for AML. We remain focused on the successful execution of the study and look forward to further exploring SENTI-202's potential."
The company's innovative approach to cell therapy, combining multiple targeting mechanisms with protective features, represents a potentially significant advance in the treatment landscape for AML and potentially other hematologic malignancies.
