Senti Bio Releases Mechanism of Action Video for First-in-Class Off-the-Shelf Logic Gated Selective CD33 OR FLT3 NOT EMCN CAR NK Cell Therapy, SENTI-202
- Promising Phase 1 trial results with no dose-limiting toxicities
- High response rate: 5 of 7 evaluable patients achieved overall response
- Strong complete remission rate: 4 of 7 patients achieved complete remission
- All complete remission patients remain in remission (4-8+ months)
- Therapy targets ~95% of AML patients through CD33/FLT3 expression
- All complete remission patients (4 of 4) achieved MRD-negative status
- Small patient sample size in preliminary results
- Relatively short follow-up period (4-8+ months)
Insights
SENTI-202 shows promising early clinical results in AML with a novel logic-gated approach designed to target cancer cells while sparing healthy stem cells.
Senti Bio's SENTI-202 represents a significant innovation in cell therapy for AML (Acute Myeloid Leukemia) and MDS (Myelodysplastic Syndrome). The therapy employs a sophisticated logic-gated approach with three key components that address fundamental challenges in treating these aggressive blood cancers.
The OR Logic Gate targets cells expressing CD33 and/or FLT3 - surface markers present in ~95% of AML patients. This dual-targeting strategy is particularly clever as it addresses both bulk leukemic blasts (predominantly CD33+) and leukemic stem cells (predominantly FLT3+). The latter are often responsible for disease relapse and are typically difficult to eradicate with conventional therapies.
What truly distinguishes SENTI-202 is the NOT Logic Gate, designed to protect healthy hematopoietic stem cells (HSCs) by recognizing Endomucin (EMCN) - a marker predominantly found on healthy HSCs but rarely on AML blasts. This selective targeting mechanism potentially solves one of the most significant limitations of current AML therapies: their inability to spare normal bone marrow progenitors.
The Phase 1 data, while preliminary, shows compelling signals of both safety and efficacy. With 4 of 7 evaluable patients achieving complete remission (all MRD-negative) and responses lasting 4+ to 8+ months, these results are noteworthy for a relapsed/refractory population. The identification of a recommended Phase 2 dose (1.5 x 109 CAR NK cells administered on Days 0,7,14 in 28-day cycles) represents an important clinical development milestone.
As an off-the-shelf allogeneic therapy, SENTI-202 offers potential advantages in manufacturing consistency and immediate availability compared to autologous approaches. While larger studies will be necessary to fully validate this approach, these early results suggest SENTI-202 could potentially address the significant unmet need for more effective and less toxic therapies in this difficult-to-treat patient population.
Video illustrates SENTI-202’s MoA, namely to selectively kill both AML blasts and leukemic stem cells (LSCs) while protecting healthy hematopoietic stem cells/ hematopoietic stem and progenitor cells (HSC/HSPCs) using its novel CD33 OR FLT3 NOT EMCN Logic-Gated gene circuit
SOUTH SAN FRANCISCO, Calif., May 08, 2025 (GLOBE NEWSWIRE) -- Senti Biosciences, Inc. (Nasdaq: SNTI) (“Senti Bio” or the “Company”), a clinical-stage biotechnology company developing next-generation cell and gene therapies using its proprietary Gene Circuit platform, today announces the release of its new animated video for its lead asset in development, SENTI-202. The video can be accessed here.
SENTI-202 is the Company’s First-in-Class Off-the-Shelf Logic Gated Selective CD33 OR FLT3 NOT EMCN CAR NK Cell Therapy product candidate designed to selectively target and eliminate CD33 and/or FLT3-expressing hematologic malignancies, such as AML and myelodysplastic syndrome (MDS), while sparing healthy bone marrow cells. SENTI-202 has three main components:
- OR Logic Gate “Kills” leukemia blasts and LSCs via CD33 OR FLT3 activating CAR (aCAR)
- CD33 and/or FLT3 expressed in ~
95% of AML patients with CD33 being predominantly expressed on bulk blasts and FLT3 on LSCs
- CD33 and/or FLT3 expressed in ~
- NOT Logic Gate “Protects” healthy HSC/HSPCs from ‘off-tumor, on-target’ effects
- Protection of HSC/HSPCs via Endomucin (EMCN) inhibitory CAR (iCAR), even when they express CD33 and/or FLT3
- EMCN found predominantly on healthy HSC/HSPC surface, rarely on AML blasts
- Calibrated release IL-15 “Enhances” SENTI-202 and host immune cell activity and persistence
Senti Bio is currently enrolling adult patients with relapsed/refractory (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 allogeneic off-the-shelf treatment for AML/MDS patients (NCT06325748).
Positive preliminary results from the ongoing Phase 1 trial as well as correlative data from patients and preclinical data supporting Logic Gate mechanism of action were recently presented at the American Association for Cancer Research (AACR) Annual Meeting 2025. The presented data demonstrated SENTI-202 was well-tolerated with no dose limiting toxicities and a maximum tolerated dose was not reached. The preliminary recommended Phase 2 dose (RP2D) was identified based on the totality of clinical data, including efficacy, as 1.5 x 109 CAR NK cells administered on Days 0,7,14 in 28-day Cycles following lymphodepleting chemotherapy. 2 of 3 patients in the preliminary RP2D cohort achieved a composite Complete Remission (cCR); 5 of the 7 best overall response evaluable patients achieved an ORR (cCR + morphologic leukemia-free state) outcome and 4 of the 7 achieved cCR (3 CR with full hematologic recovery, and 1 CRh (CR with partial hematologic recovery)). 4 of 4 cCR patients were MRD- (Measurable Residual Disease Negative) as assessed by local standard of care. All cCR patients continue in remission with follow-ups ranging from 4+ to 8+ months ongoing.
The SENTI-202 animated mechanism of action video is now available on the Company’s website, here.
About Senti Bio
Senti Bio 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 its synthetic biology platform to engineer Gene Circuits into new medicines with enhanced precision and control. These Gene Circuits are designed to precisely kill cancer cells, to spare healthy cells, to increase specificity to target tissues, and/or to be controllable even after administration. The Company’s wholly-owned pipeline is comprised of cell therapies engineered with Gene Circuits to target challenging liquid and solid tumor indications. Senti’s Gene Circuits have been shown preclinically to work in both NK and T cells. Senti Bio has also preclinically demonstrated the potential breadth of Gene Circuits in other modalities and diseases outside of oncology, and continues to advance these capabilities through partnerships.
Forward-Looking Statements
This press release and document contain certain statements that are not historical facts and are considered forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. These forward-looking statements generally are identified by the words “believe,” “could,” “predict,” “continue,” “ongoing,” “project,” “expect,” “anticipate,” “estimate,” “intend,” “strategy,” “future,” “opportunity,” “plan,” “may,” “should,” “will,” “would,” “will be,” “will continue,” “will likely result,” “forecast,” “seek,” “target” and similar expressions that predict or indicate future events or trends or that are not statements of historical matters. Forward-looking statements are predictions, projections, and other statements about future events that are based on current expectations of Senti Bio’s management and assumptions, whether or not identified in this document, and, as a result, are subject to risks and uncertainties. Forward-looking statements include, but are not limited to, expectations regarding Senti Bio’s growth, strategy, progress and timing of its clinical trials for SENTI-202;the timing of availability of data from the ongoing Phase 1 clinical trial of SENTI-202; the ability of any product candidate to perform in humans in a manner consistent with nonclinical, preclinical or previous clinical study data; expectations regarding the anticipated dosing of patients and availability of data from clinical trials, and the timing thereof. These forward-looking statements are provided for illustrative purposes only and are not intended to serve as and must not be relied on by any investor as, a guarantee, an assurance, a prediction, or a definitive statement of fact or probability. Actual events and circumstances are difficult or impossible to predict and will differ from assumptions. Many actual events and circumstances are beyond the control of Senti Bio. Many factors could cause actual future results to differ materially from the forward-looking statements in this document, including but not limited to: (i) changes in domestic and foreign business, market, financial, political and legal conditions, (ii) changes in the competitive and highly regulated industries in which Senti Bio operates, variations in operating performance across competitors, changes in laws and regulations affecting Senti Bio’s business, (iii) the ability to implement business plans, forecasts and other expectations, (iv) the risk of downturns and a changing regulatory landscape in Senti Bio’s highly competitive industry, (v) risks relating to the uncertainty of any projected financial information with respect to Senti Bio, (vi) risks related to uncertainty in the timing or results of Senti Bio’s clinical trial start up, clinical studies, patient enrollment, and GMP manufacturing startup activities, (vii) Senti Bio’s dependence on third parties in connection with clinical trial startup, clinical studies, and GMP manufacturing activities, (viii) risks related to delays and other impacts from macroeconomic and geopolitical events, increasing rates of inflation and rising interest rates on business operations, (ix) risks related to the timing and utilization of the grant from CIRM, and (x) the success of any future research and development efforts by Senti Bio. The foregoing list of factors is not exhaustive. You should carefully consider the foregoing factors and the other risks and uncertainties described in the “Risk Factors” section of Senti Bio’s most recent periodic report filed with the U.S. Securities and Exchange Commission (“SEC”), and other documents filed by Senti Bio from time to time with the SEC. These filings identify and address other important risks and uncertainties that could cause actual events and results to differ materially from those contained in the forward-looking statements in this document. There may be additional risks that Senti Bio does not presently know, or that Senti Bio currently believes are immaterial that could also cause actual results to differ from those contained in the forward-looking statements in this document. Forward-looking statements speak only as of the date they are made. Senti Bio anticipates that subsequent events and developments may cause Senti Bio’s assessments to change. Except as required by law, Senti Bio assumes no obligation to update publicly any forward-looking statements, whether as a result of new information, future events, or otherwise.
Availability of Other Information About Senti Biosciences, Inc.
For more information, please visit the Senti Bio website at www.sentibio.com or follow Senti Bio on X (@SentiBio) and LinkedIn (Senti Biosciences). Investors and others should note that we communicate with our investors and the public using our company website (www.sentibio.com), including, but not limited to, company disclosures, investor presentations and FAQs, Securities and Exchange Commission filings, press releases, public conference call transcripts and webcast transcripts, as well as on X and LinkedIn. The information that we post on our website or on X or LinkedIn could be deemed to be material information. As a result, we encourage investors, the media and others interested to review the information that we post there on a regular basis. The contents of our website or social media shall not be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended.
Investor Contact:
JTC Team, LLC
Jenene Thomas
(908) 824-0775
SNTI@jtcir.com
FAQ
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