Senti Bio Announces FDA Clearance of IND Application for SENTI-202 for the Treatment of Relapsed or Refractory Hematologic Malignancies Including Acute Myeloid Leukemia
– First patient in Phase 1 clinical trial expected to be treated in Q2 2024 –
– Initial clinical efficacy data expected by year-end 2024 and durability data expected in 2025 –
– SENTI-202 is a potential first-in-class off-the-shelf CAR-NK cell therapy using Logic Gated Gene Circuits to selectively target cancer cells while sparing healthy bone marrow cells –
SOUTH SAN FRANCISCO, Calif., Dec. 22, 2023 (GLOBE NEWSWIRE) -- Senti Biosciences, Inc. (Nasdaq: SNTI) (“Senti Bio”), a clinical stage biotechnology company developing next-generation cell and gene therapies using its proprietary Gene Circuit platform, today announced that it received clearance of its Investigational New Drug (IND) application from the U.S. Food and Drug Administration (FDA) for SENTI-202, an off-the-shelf chimeric antigen receptor natural killer (CAR-NK) cell therapy product candidate designed to selectively target and eliminate CD33 and/or FLT3 expressing hematologic malignancies while sparing healthy bone marrow cells.
The Company plans to initiate a Phase 1 clinical trial of SENTI-202 in 2024 in multiple sites in the United States and Australia, and expects to treat the first patient in the second quarter of 2024. The dose finding trial will evaluate two dose levels, either 1 or 1.5 billion SENTI-202 cells, administered after lymphodepleting conditioning in adult patients with relapsed or refractory (r/r) CD33 and/or FLT3 expressing hematologic malignancies, including acute myeloid leukemia (AML). Initial dosing will consist of three doses administered weekly following lymphodepletion, with the option to receive continuation cycles of lymphodepletion and SENTI-202 cells based on safety and efficacy data.
“Clearance of our IND application for SENTI-202 is a tremendous milestone and marks an important achievement for Senti as we transition to a clinical-stage therapeutics company,” said Timothy Lu, MD, PhD, Chief Executive Officer and Co-Founder of Senti Bio. “Our team has dedicated immense time and resources to developing our Gene Circuit technology from an initial synthetic biology hypothesis to what is now a tangible product for cancer patients. We look forward to initiating Senti’s first clinical trial and continuing our strong momentum into next year.”
A limitation of many existing cancer therapies, according to the Company, is that current treatments cannot precisely distinguish cancer cells from healthy cells, leading to side effects and limited efficacy due to dosing limitations from these safety events. Furthermore, AML is polyclonal and heterogenous, and requires multiple antigens to be targeted in order to achieve deep and durable responses. SENTI-202 utilizes proprietary Logic Gating technology designed to overcome AML disease heterogeneity by targeting both the cancer cells and leukemic stem cells through its OR GATE, which can kill cancer cells that express either CD33 and/or FLT3. SENTI-202 also incorporates the NOT GATE that recognizes healthy cells through a protective antigen, and spares healthy bone marrow cells even if they express CD33 and/or FLT3. Finally, SENTI-202 expresses a proprietary calibrated release IL15, which has the ability to enhance both the CAR-NK cells, as well as patient immune cell function in the leukemic milieu to further enhance activity. Senti Bio believes this approach can lead to more effective and durable responses in patients.
“SENTI-202 has been systematically engineered to potentially overcome the key limitations of current AML therapies, namely the need to address AML heterogeneity and to protect healthy marrow cells from on-target and off-tumor killing,” said Kanya Rajangam, MD, PhD, Head of Research & Development and Chief Medical Officer of Senti Bio. “Our trial design incorporates lessons learnt from clinical experiences with other AML cell therapies and includes disease-specific lymphodepletion, multiple high doses of CAR-NK cells, as well as multiple treatment cycles. We are excited to begin this trial and deliver a potential treatment to patients who currently have no approved therapies and very poor prognosis.”
The Company expects to disclose initial efficacy data from the Phase 1 trial by year-end 2024 and durability data in 2025. Through Senti Bio’s previously announced agreement with GeneFab, the Company has prepaid the majority of manufacturing-related expenses through the completion of the Phase 1 trial.
SENTI-202 is a Logic Gated off-the-shelf CAR-NK cell therapy product candidate designed to selectively target and eliminate CD33 and/or FLT3 expressing hematologic malignancies, such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), while sparing healthy bone marrow cells. SENTI-202 has three main components. First, the OR GATE, which is an activating CAR that targets CD33 and FLT3. By targeting either or both of these antigens, SENTI-202 could effectively kill both the leukemic blasts and leukemic stem cells that form an important basis for AML disease. Second, the NOT GATE, which is designed to recognize the healthy cells and protect those healthy cells from being killed. Third, the calibrated-release IL-15 technology, which is designed to significantly increase cell persistence, expansion and activity of both the CAR- NK cells and the host immune cells. The NK cells used to construct SENTI-202 are sourced from healthy adult donors, which have been screened based on a set of criteria that reflect manufacturability and product quality, and are then cryopreserved prior to use in manufacturing to minimize variability. Senti Bio is currently enrolling adult patients with r/r CD33 and/or FLT3 expressing heme malignancies in a Phase 1 clinical trial for SENTI-202, which can be a potential first-in-class allogenic treatment for AML/MDS patients.
About Acute Myeloid Leukemia
Acute myeloid leukemia is a cancer of the blood and bone marrow and is the most common type of acute leukemia in adults. It is estimated there will be 20,380 new cases of AML in the United States in 2023. The five-year survival rate for these patients is approximately 30%. AML is currently treated with chemotherapy, targeted therapies, and/or allogeneic or autologous stem cell transplant. For patients with relapsed or refractory AML, there are few treatment options and median overall survival is typically less than seven months.
About Senti Bio
Senti 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. These Gene Circuits work in many different genetic medicine modalities, including T cells, NK cells, induced pluripotent stem cells (iPSCs), and gene therapy. 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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