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DRUG:

SENTI-202

i
Other names: SENTI-202
Associations
Trials
Company:
Senti Bio
Drug class:
NK cell stimulant, CD33 modulator, FLT3 modulator
Related drugs:
Associations
Trials
6ms
Enrollment open
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cytarabine • fludarabine IV • SENTI-202
8ms
New P1 trial
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cytarabine • fludarabine IV • SENTI-202
1year
Calibrated Release IL15 Bivalent CD33 and/or FLT3 and NOT Emcn Logic Gated Gene Circuit CAR-NK Cell Therapy (SENTI-202) in Venetoclax Resistant Patient Derived Xenograft Acute Myeloid Leukemia Models (ASH 2023)
Our initial PDX studies used clinically relevant VEN/HMA-r AML PDX cells (designated as PDX1) obtained from a patient with FLT3-ITD, GATA2, and NRAS mutations, who initially responded to VEN/decitabine treatment but later relapsed. In conclusion, CAR-NK cells expressing the SENTI-202 OR Gate and crIL15 demonstrate robust anti-tumor activity against primary AML cells within in vitro cytotoxicity assays and in vivo AML PDX models, including VEN-r AML. These promising preclinical results highlight the potential of SENTI-202 as a targeted and selective therapy for AML, offering a new avenue for overcoming the challenges posed by the heterogeneity of the AML proteomic landscape.
Clinical
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FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IFNG (Interferon, gamma) • TNFA (Tumor Necrosis Factor-Alpha) • CD33 (CD33 Molecule) • GATA2 (GATA Binding Protein 2) • IL15 (Interleukin 15) • PDX1 (Pancreatic And Duodenal Homeobox 1)
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NRAS mutation • FLT3-ITD mutation • FLT3 expression
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Venclexta (venetoclax) • decitabine • SENTI-202
over1year
Preclinical development of SENTI-202, an off-the-shelf logic gated CAR-NK cell therapy, for the treatment of CD33/FLT3+ hematologic malignancies including AML (AACR 2023)
crIL-15 expression yielded functional pSTAT5 signaling and increased persistence of SENTI-202 in vitro and in vivo. These results demonstrate the antitumor activity and tolerability of SENTI-202 and warrant further clinical development as a novel therapeutic option for patients with CD33+ and/or FLT3+ tumors.
Preclinical
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FLT3 (Fms-related tyrosine kinase 3) • CD33 (CD33 Molecule) • IL15 (Interleukin 15)
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SENTI-202
2years
Senti-202, a Selective, Off-the-Shelf, Preclinical CAR-NK Cell Therapy with CD33 and/or FLT3 Activating CAR, Healthy Cell Protection from Endomucin (EMCN) Inhibitory CAR and Calibrated Release IL-15 for Hematologic Malignancies Including AML (ASH 2022)
In summary, preclinical evaluation of SENTI-202 demonstrated selective killing of CD33 and/or FLT3 expressing AML cell lines while protecting healthy HSCs and HPCs. This selectivity is imparted by the novel logic-gated gene circuit engineered into healthy adult NK cells. Clinical evaluation of SENTI-202 is planned to evaluate the safety and efficacy in patients with hematologic malignancies with high unmet need, including AML.
Preclinical
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FLT3 (Fms-related tyrosine kinase 3) • CD33 (CD33 Molecule) • IL15 (Interleukin 15)
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FLT3 expression
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SENTI-202