Senti Biosciences (Senti Bio)’s SENTI-202, an investigational allogeneic chimeric antigen receptor natural killer (CAR-NK) cell therapy candidate intended to treat acute myeloid leukemia (AML) and myelodysplastic syndrome, has received clearance of an investigational new drug application (IND) from the FDA.1
In light of the IND clearance, Senti Bio anticipates the launch of a multicenter clinical trial in hematological malignancies this year, with the first patient expected to receive the therapy within 2024’s second quarter. The study, which will take place in both the United States and Australia, will seek to recruit patients with relapsed/refractory hematological malignancies that express either CD33, FLT3, or both CD33 and FLT3. SENTI-202 will be administered at doses of either 1 billion or 1.5 billion CAR-NK cells, depending on a patients’ assigned dose level in the trial. Initially, patients will receive 3 doses weekly after undergoing lymphodepletion; additional cycles of lymphodepletion and doses of the therapy may be administered to patients depending on safety and efficacy outcomes. The company noted that it expects to announce initial clinical efficacy results from the trial by the end of 2024 and durability results in 2025.
SENTI-202 incorporates logic gating based on the company’s proprietary Gene Circuit platform. It targets both CD33 and FLT3 with the company’s “OR” logic gate, while incorporating a “NOT” logic gate to spare cells expressing EMCN.2
“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,” Timothy Lu, MD, PhD, the chief executive officer and co-founder of Senti Bio, said in a statement.1 “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.”
- Senti Bio's investigational allogeneic CAR-NK cell therapy, SENTI-202, received FDA clearance for an IND application.
- A multicenter clinical trial for hematological malignancies, including relapsed/refractory cases expressing CD33, FLT3, or both, is expected to commence in 2024's second quarter, with initial efficacy results anticipated by the end of 2024.
- SENTI-202 incorporates logic gating based on the company’s proprietary Gene Circuit platform.
In August 2023, Senti Bio’s manufacturing facility was acquired by private equity firm Celadon Partners, which established GeneFab, a new independent manufacturing company.3 As part of the transaction agreement, GeneFab will carry out clinical manufacturing of SENTI-202 and other CAR-NK products in Senti Bio’s pipeline under a service contract. In December 2023, Senti Bio noted that the majority of manufacturing–related expenses necessary to complete the phase 1 study for SENTI-202 have been prepaid.
“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,” Kanya Rajangam, MD, PhD, the head of Research and Development and the chief medical officer of Senti Bio, added to the statement.1 “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 IND clearance follows an announcement from the company made nearly a year ago that it would be prioritizing the development of SENTI-202 and SENTI-401.2 SENTI-401, another investigational NK cell therapy, is intended to treat colorectal cancer and other CEA tumor antigen-expressing solid tumors. It remains in preclinical development.4 At the same time, Senti Bio also announced intention to deprioritize development of SENTI-301A, a preclinical GPC3-targeted CAR-NK therapy intended to treat hepatocellular carcinoma (HCC) which does not incorporate the OR and NOT logic gates, until it is able to establish a strategic geographic partnership for its continued development for regions in Asia where HCC is more common than it is in the United States.2,4 In November 2023, Senti Bio announced that it had established a strategic collaboration with Celest Therapeutics for the further development of SENTI-301A in China.5
1. Senti Bio announces FDA clearance of IND application for SENTI-202 for the treatment of relapsed or refractory hematologic malignancies including acute myeloid leukemia. News release. Senti Biosciences, Inc. December 22, 2023. Accessed January 4, 2024. https://investors.sentibio.com/news-releases/news-release-details/senti-bio-announces-fda-clearance-ind-application-senti-202
2. Senti Bio announces pipeline prioritization to focus on logic gated cell therapies; updates cash runway guidance. News release. Senti Biosciences, Inc. January 27, 2023. Accessed January 4, 2024. https://investors.sentibio.com/news-releases/news-release-details/senti-bio-announces-pipeline-prioritization-focus-logic-gated
3. Senti Bio announces closing of transaction leveraging its CMC capabilities into a cell and gene therapy manufacturing innovation business backed by celadon partners. News release. Senti Biosciences, Inc. August 10, 2023. Accessed January 4, 2023. https://investors.sentibio.com/news-releases/news-release-details/senti-bio-announces-closing-transaction-leveraging-its-cmc
4. Pipeline. Senti Biosciences, Inc. Website. Accessed January 30,2023. https://www.sentibio.com/pipeline
5. Senti Bio announces new strategic collaboration with Celest therapeutics for clinical development of SENTI-301A in China. News release. Senti Biosciences, Inc. November 6, 2023. Accessed January 4, 2024. https://investors.sentibio.com/news-releases/news-release-details/senti-bio-announces-new-strategic-collaboration-celest