Senti Bio Announces Publication of SENTI-202 Preclinical Data Demonstrating Potential of Logic-Gated CAR-NK Cell Therapy for the Treatment of Acute Myeloid Leukemia (AML)

Senti Biosciences, Inc. (Nasdaq: SNTI) (“Senti Bio”), a biotechnology company developing next-generation cell and gene therapies using its proprietary Gene Circuit platform, today announced the publication of preclinical data demonstrating the ability of natural killer (NK) cells engineered with multi-input Gene Circuits to selectively target and eliminate leukemic cells, including both blasts and leukemic stem cells, while sparing healthy stem cells. The data was published in Cell Reports on April 25, 2024.

The publication, titled “Precision off-the-shelf natural killer cell therapies for oncology with logic-gated gene circuits,” demonstrates the activity of logic-gated NK cells in vitro and in vivo preclinical studies.

“AML, an aggressive form of leukemia with a poor prognosis, has long presented a challenge for targeted therapies due to the lack of a single tumor-associated antigen that distinguishes cancer cells from healthy cells,” said Timothy Lu, MD, PhD, Chief Executive Officer and Co-Founder of Senti Bio. “By harnessing the power of logic-gated NK cells, this preclinical data demonstrates SENTI-202’s ability to precisely target and eliminate leukemic cells while sparing healthy stem cells, thereby illustrating the potential to minimize the risk of harmful side effects and maximizing the potential for deep therapeutic efficacy. We are encouraged about the possibility of translating these findings into our Phase 1 clinical trial of SENTI-202, which is on track to begin this quarter, offering new hope for patients with limited options today."

The peer-reviewed publication describes preclinical studies of engineered NK cells with a Gene Circuit consisting of chimeric antigen receptors (CARs) controlled by OR and NOT logic gates. This approach allows NK cells to detect and respond to multiple antigen inputs, enabling precise targeting of AML cells while protecting healthy cells. Using the OR gate, NK cells were able to kill a range of AML cells, including leukemic stem cells and blasts, by recognizing FLT3 and/or CD33, which are validated therapeutic targets for AML. The NOT gate component of the Gene Circuit protected healthy HSCs by reducing CAR-mediated killing through an inhibitory CAR recognizing the endomucin antigen, which is selectively expressed on healthy HSCs but not cancer cells. In preclinical mouse models, the engineered NK cells killed multiple AML subtypes while protecting primary hematopoietic stem cells (HSCs).

This data supports the design of Phase 1 clinical trial of SENTI-202, a potential first-in-class, off-the-shelf logic-gated CAR-NK investigational cell therapy for the treatment of AML. Senti Bio is on track to initiate patient dosing in the second quarter of 2024, with initial efficacy data anticipated by year-end 2024 and initial durability data following in 2025.

About Senti BioSenti Biosciences is a biotechnology company developing a new generation of cell and gene therapies for patients living with incurable diseases. To achieve this, Senti Bio is leveraging a synthetic biology platform called Gene Circuits to create therapies with enhanced precision and control. These Gene Circuits are designed to precisely kill cancer cells, spare healthy cells, increase specificity to target cells and control the expression of drugs even after administration. The Company’s wholly-owned pipeline utilizes off-the-shelf chimeric antigen receptor natural killer (CAR-NK) cells, outfitted with Gene Circuits, to target challenging liquid and solid tumor indications. Senti Bio has also preclinically demonstrated the potential breadth Gene Circuits in other modalities, diseases outside of oncology, and continues to advance these capabilities through partnerships with Spark Therapeutics and BlueRock Therapeutics.

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