SENTI-202 for the Treatment of Acute Myeloid Leukemia (AML)
AML: A Significant Unmet Medical Need
Almost 10% of new cancer cases in the United States each year are hematologic malignancies, including leukemia, lymphoma and myeloma. AML is a type of acute leukemia characterized by an accumulation of malignant immature white blood cells. It is the most common type of acute leukemia in adults, constituting 80% to 85% of cases, and is the second most common—as well as the deadliest—in children. Due to the absence of highly efficacious therapies, AML has poor prognosis with a low five-year survival rate at just 30.5%.
SENTI-202 Product Design
SENTI-202 is a potential first-in-class Logic Gated off-the-shelf chimeric antigen receptor natural killer (CAR-NK) investigational cell therapy. It has been designed to incorporate three chimeric proteins using a Logic Gated Gene Circuit to address the key limitation of NK cellular therapies evaluated in clinical trials. This includes a bivalent (OR gate) activating CAR (aCAR) that is triggered independently by either one or both CD33 (validated AML target) and/or FLT3.
SENTI-202 includes a NOT gate in the Gene Circuit or an inhibitory CAR (iCAR) to protect the healthy cells from potential aCAR-mediated on-target/off-tumor toxicity to augment the NK cell’s inherent healthy cell protective activities. The iCAR is designed to recognize the healthy cell surface protein endomucin (EMCN). EMCN was chosen as the protective antigen using a multi-step unbiased bioinformatics pipeline designed to identify a cell surface antigen specifically expressed on healthy cells but absent on AML tumor cells.
SENTI-202 Clinical Trial Design
The Phase 1 clinical trial of SENTI-202 is enrolling across multiple sites in the United States and Australia (NCT06325748). The study evaluates two dose levels of SENTI-202 (1 billion and 1.5 billion CAR NK cells per dose) administered as three weekly doses (days 0, 7, 14) of a 28 day cycle following fludarabine/cytarabine (Ara-C) based lymphodepletion in patients with relapsed or refractory CD33 and/or FLT3 hematologic malignancies including AML. Multiple cycles are permitted per protocol.
Clinical Trial Access
At Senti Bio, we are committed to ensuring the safety of the patients who take part in our clinical trials and to upholding the highest ethical, scientific, and clinical standards in all our research initiatives.
Clinical studies are an important part of the drug discovery process and a critical research tool for advancing patient care and bringing new medicines to patients and families who need them. Enrollment in one of our clinical studies is the primary way in which we can provide patients access to our investigational drugs prior to their potential approval by regulatory authorities, such as the United States Food and Drug Administration (FDA). Clinical studies are required to demonstrate that an investigational medicine meets necessary safety and effectiveness standards before it is approved and becomes commercially available to the public. Patients who participate in clinical studies help advance new scientific discoveries and make better future treatments possible.
Senti sponsored clinical trials are designed and conducted in accordance with applicable laws and regulations, as well as recognized medical and ethical standards so that the health, well-being, and safety of research participants are protected.
For more information about the SENTI-202 clinical trial, please click here.
If you are a patient or an investigator interested in one of our clinical trials, please e-mail info@sentibio.com. Thank you for your interest in Senti Bio!
SENTI-301A for the Treatment of GPC3 positive solid tumors, such as Hepatocellular Carcinoma (HCC)
SENTI-301A is a multi-armed off-the-shelf healthy donor derived chimeric antigen receptor natural killer (CAR-NK) cell therapy product candidate designed for the treatment of GPC3 positive tumors. SENTI-301A is armed with our proprietary crIL-15 Gene Circuit, intended to simultaneously stimulate surrounding immune cells and promote NK cell expansion, persistence and tumor killing.
In partnership with Celest Therapeutics, we anticipate initiating clinical studies in China in patients with hepatocellular carcinoma (HCC) in 2024.
