Senti Bio Begins Phase 1 Trial of SENTI-202 for Blood Cancer Treatment

Senti Biosciences, Inc. has initiated patient dosing in a Phase 1 clinical trial for SENTI-202, a novel Logic Gated off-the-shelf CAR-NK cell therapy, aimed at treating relapsed or refractory hematologic cancers, including acute myeloid leukemia (AML). As the most common acute leukemia in adults, AML impacts the blood and bone marrow, necessitating more advanced treatments. SENTI-202 is engineered to selectively target and destroy CD33 and/or FLT3 expressing cancer cells while preserving healthy bone marrow cells.

The launch of this clinical trial represents a significant step forward for Senti Biosciences in their mission to improve treatment options for AML patients, a group with limited alternatives and generally poor outcomes. According to Kanya Rajangam, MD, PhD, Chief Medical Officer of Senti Bio, the engineered design of SENTI-202 aims to tackle the complexities of AML while protecting healthy cells, thus addressing limitations of current therapies.

This Phase 1 trial is being conducted at multiple sites in the United States and Australia, enrolling adult patients with relapsed or refractory CD33 and/or FLT3 expressing hematologic malignancies, including AML. The study is testing two dosage levels of SENTI-202: 1 billion and 1.5 billion cells, administered in cycles that include three weekly doses following disease-specific lymphodepleting conditioning. Patients may receive multiple cycles based on safety and efficacy outcomes.

Senti Bio has secured a manufacturing agreement with GeneFab, prepaying most of the trial's production costs. This collaboration supports the company's efforts to advance the clinical development of SENTI-202.

SENTI-202 is structured with three key components: the OR GATE, the NOT GATE, and calibrated-release IL-15 technology. The OR GATE activates the CAR by targeting CD33 and FLT3, which could potentially eliminate both leukemic blasts and stem cells integral to AML. The NOT GATE is designed to identify and protect healthy cells, preventing them from being destroyed. The IL-15 technology enhances the persistence, expansion, and activity of the CAR-NK cells and the host immune cells. The NK cells used for SENTI-202 are derived from healthy adult donors and are cryopreserved to minimize variability.

Senti Bio's preclinical data has shown promise in using Logic Gated CAR-NK cell therapy for treating AML. The ongoing Phase 1 clinical trial aims to substantiate these findings in a clinical setting, with initial efficacy data anticipated by the end of 2024 and durability data expected in 2025.

AML remains a severe and common form of acute leukemia in adults, with about 20,800 new cases projected in the United States for 2024. The five-year survival rate for AML patients stands at approximately 30%, and the prognosis is particularly bleak for those with relapsed or refractory AML, who typically have a median overall survival of less than seven months. Current treatment strategies include chemotherapy, targeted therapies, and stem cell transplants.

Senti Bio aims to revolutionize cell and gene therapies for incurable diseases through their Gene Circuit platform, which provides enhanced precision and control. Their pipeline includes off-the-shelf CAR-NK cells designed to target challenging cancer indications. The company also explores the potential of Gene Circuits in other diseases through partnerships with Spark Therapeutics and BlueRock Therapeutics.