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0001854270FALSENasdaq00018542702025-04-282025-04-28











UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
___________________________________
FORM 8-K
___________________________________
CURRENT REPORT
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): (April 28, 2025)
___________________________________
SENTI BIOSCIENCES, INC.
(Exact name of Registrant as specified in its charter)
___________________________________
Delaware 001-40440 86-2437900
(State or other jurisdiction
of incorporation)
(Commission
File Number)
(IRS Employer
Identification No.)
2 Corporate Drive, First Floor
South San Francisco, California 94080
(Address of principal executive offices including zip code)
Registrant’s telephone number, including area code: (650) 239-2030

(Former name or former address, if changed since last report)
___________________________________
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))
Securities registered pursuant to Section 12(b) of the Act:
Title of each class
Trading
Symbol
Name of each exchange
on which registered
Common Stock, par value $0.0001 per share SNTI
The Nasdaq Capital Market
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company ☒


Item 2.02 Results of Operations and Financial Condition.
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☒ In connection with the press release described in Item 8.01 below (the “Press Release”), on April 28, 2025, Senti Biosciences, Inc. (the “Company”) provided, on a preliminary and unaudited basis, certain estimated financial results for the quarter ended March 31, 2025. The preliminary estimates are based on currently available information and does not present all necessary information for a complete understanding of the Company’s financial condition as of March 31, 2025 or the Company’s results of operations for the quarter ended March 31, 2025.

Item 7.01 Regulation FD Disclosure.
As reported under Item 8.01 of this Current Report on Form 8-K, on April 28, 2025, the Company issued the Press Release to announce certain corporate updates including preliminary data from a Phase 1 clinical trial of SENTI-202, a potential first-in-class off-the-shelf Logic Gated selective CD33 OR FLT3 NOT EMCN chimeric antigen receptor natural killer investigational cell therapy, for the treatment of relapsed/refractory hematologic malignancies including acute myeloid leukemia (the “Clinical Data”). As previously announced, the Clinical Data was presented on April 27, 2025 during a presentation in the Clinical Trials Oral Minisymposium at the AACR Annual Meeting 2025 in an abstract titled, “First-in-human, multicenter study of SENTI-202, a CD33/FLT3 selective off-the-shelf logic gated CAR NK cell therapy in hematologic malignancies including AML: Clinical data.” The Company will hold a conference call regarding this announcement, including the Clinical Data, on April 28, 2025. A copy of the supplemental presentation which will be referenced during the conference call and posted on the Company’s website is furnished herewith as Exhibit 99.1 to this Current Report on Form 8-K and is incorporated by reference herein.

The information in this Item 7.01 of this Current Report on Form 8-K shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that Section, or incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as shall be expressly set forth by specific reference in any such filing.

Item 8.01. Other Events.
As reported under Item 7.01 of this Current Report on Form 8-K, on April 28, 2025, the Company issued the Press Release to announce corporate updates, including the Clinical Data. The Press Release is filed herewith as Exhibit 99.2 and is incorporated by reference herein.

Item 9.01 Financial Statements and Exhibits.
(d) Exhibits

Exhibit No. Description
99.1
99.2
104 Cover Page Interactive Data File (embedded within the Inline XBRL document)



SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
SENTI BIOSCIENCES, INC.
Date: April 28, 2025 By: /s/ Timothy Lu
Name: Timothy Lu
Title: Chief Executive Officer


EX-99.1 2 ex991snti_conferencecall.htm EX-99.1 ex991snti_conferencecall
NASDAQ: SNTI | sentibio.com SENTI-202: Positive Preliminary Results in the Treatment of Relapsed/Refractory Hematologic Malignancies Including AML in Ongoing Phase 1 Trial (SENTI-202-101) April 28, 2025 Conference Call and Webcast


 
Forward Looking Statements This presentation contains forward-looking statements of Senti Biosciences, Inc. ("we," "us," "our”) within the meaning of the Private Securities Litigation Reform Act of 1995. Statements we make in this presentation may include statements which are not historical facts and are considered forward-looking 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, which are usually identified by the use of words such as “anticipates,” “believes,” “estimates,” “expects,” “future,” “objective,” “opportunity,” “potential,” “proposed,” “targets,” “intends,” “may,” “plans,” “projects,” “seeks,” “should,” “will,” and variations of such words or similar expressions. We intend these forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act and Section 21E of the Securities Exchange Act and are making this statement for purposes of complying with those safe harbor provisions. These forward-looking statements, including statements regarding attributes and benefits of our technology platform and of our product candidates, including their therapeutic potential; our cash runway; clinical trials, including trial design and endpoints, our ability to achieve such endpoints, our plans to transition our Phase 1 clinical trial of SNTI-202 to a pivotal study; and our manufacturing process and its potential benefits, reflect our current views about our plans, intentions, expectations, strategies and prospects, which are based on the information currently available to us and on assumptions we have made. These forward-looking statements are provided for illustrative purposes only and are not intended to serve as, and must not be relied on as a guarantee, an assurance, a prediction or a definitive statement of fact or probability. Although we believe that our plans, intentions, expectations, strategies and prospects as reflected in or suggested by those forward-looking statements are reasonable, we can give no assurance that the plans, intentions, expectations or strategies will be attained or achieved. Many actual events and circumstances are difficult or impossible to predict, are beyond our control and will differ from assumptions. Furthermore, actual results may differ materially from those described in the forward-looking statements and will be affected by a variety of risks and factors that are beyond our control including, without limitation, the risk that results observed in studies of our product candidates, including preclinical studies and future clinical trials of any of our product candidates, will not be observed in ongoing or future studies involving these product candidates, the risk that we may cease or delay clinical development of any of our product candidates for a variety of reasons (including requirements that may be imposed by regulatory authorities on the initiation or conduct of clinical trials, the amount and type of data to be generated, or otherwise to support regulatory approval, difficulties or delays in subject enrollment and continuation in current and planned clinical trials, difficulties in manufacturing or supplying our product candidates for preclinical and clinical testing, and any adverse events or other negative results that may be observed during preclinical or clinical development), our ability to obtain, maintain and protect our intellectual property, our dependence on third parties for development and manufacture of product candidates, our ability to manage expenses and to obtain additional funding when needed to support our business activities and establish and maintain strategic business alliances and new business initiatives, the impacts of macroeconomic and geopolitical events, including various global conflicts, increasing rates of inflation and rising interest rates on business operations and expenses, and the risk that our product candidates may not produce therapeutic benefits or may cause other unanticipated adverse effects, as well as those set forth in the section titled “Risk Factors” of Senti Bio’s most recently filed periodic report, and other documents filed by Senti Bio from time to time with the SEC. Except as required by law, we assume no obligation to update publicly any forward-looking statements, whether as a result of new information, future events or otherwise. This presentation shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation, or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction. Trademarks This document contains references to trademarks, trade names and service marks belonging to other entities. Solely for convenience, trademarks, trade names and service marks referred to in this presentation may appear without the ® or TM symbols, but such references are not intended to indicate, in any way, that the applicable owner will not assert, to the fullest extent under applicable law, its rights to these trademarks and trade names. We do not intend our use or display of other entities’ trade names, trademarks or service marks to imply a relationship with, or endorsement or sponsorship of us by, any other entities. 2


 
Company Highlights 3 • Demonstrated positive preliminary efficacy data in ongoing Phase 1 trial for treatment in R/R AML • Dose finding completed, CR* and durability data presented at AACR 2025 along with correlative data supporting Logic Gating mechanism of action Pipeline of NK and T cells for hard-to-treat cancers Potential best-in-class Logic-Gated cell therapy pipeline, initially targeting AML Lead program SENTI-202 First-in-Class Off-the-Shelf Logic-Gated Selective CD33 OR FLT3 NOT EMCN CAR NK Cell Therapy Investment from Leading Healthcare Institutional InvestorsPlatform technology can be utilized with both NK and T cell therapies Gene Circuits platform provides blockbuster opportunity to selectively and effectively target liquid and solid tumors while sparing healthy cells *CR: Complete Remission Scalable off-the-shelf manufacturing process streamlines treatment


 
Cancer Cells Healthy Cells Commercially approved CAR T cell therapies Recognize Single Antigen Target Single Antigen Target may be found on both cancer and healthy cells KILL KILL Biologics (ADC/TCE)* Logic Gates in Cell Therapy 4 Enable CAR-NK / CAR-T Cells to Address Broad Liquid and Solid Tumor Applications Non-Logic Gate Approaches Senti Bio’s Logic Gate Approach Cancer Cells Healthy Cells SENTI-202 and Other Undisclosed Programs KILL PROTECT (DO NOT KILL) OR Gate (aCAR) Kill if you see Antigens CD33 or FLT3 NOT Gate (iCAR) Do Not Kill if you see Antigen EMCN even if you see CD33 or FLT3 Recognizes Multiple Antigen Targets *ADC: antibody drug conjugate; TCE: T cell engagers


 
Acute Myeloid Leukemia (AML) Is an Aggressive Leukemia with Poor Prognosis • 20,800 newly diagnosed AML patients in US every year1 • ~60% patients experience relapse or death within 12 months2 AML Estimated Disease Burden Relapsed/Refractory AML Patient Outcome Effective Anti-AML Therapies Need To: • Current standard of care responses4,5 • CR rate ~15-25% • CR/CRh rate ~20-33% Median survival of 5.3 months3 5-year survival rate is 12.6%3 Target heterogenous clones / leukemia stem cells (LSCs)6 Selectively kill AML blasts and LSCs, and spare HSCs To achieve deep / MRD negative CR Leading to durable remissions / longer survival4,6 To support normal blood cell count recovery Leading to improved prognosis / longer survival7 1 2 CR: complete remission; CRh: complete remission with partial hematologic recovery; MRD: measurable residual disease; HSC: hematopoietic stem cell 1SEER 2024; 2Tenold Frontiers in Oncology 2021; 3Brandwein AJBR 2020; 4Dohner Blood 2022; 5USPI Idhifa, Xospata, Tibsovo; 6Zeijlemaker Leukemia 2019; 7Innes Blood 2018 5


 
SENTI-202: Intelligently Designed CAR-NK May Overcome Limitations of Current Therapies Against AML LSC: Leukemia stem cell; HSC: hematopoietic stem cell; HSPC: hematopoietic stem and progenitor cell 6 Bivalent CD33 and/or FLT3 activating CAR Calibrated release IL- 15 Endomucin inhibitory CAR to protect healthy cells Persistence, activation of CAR-NK and immune cells Healthy NK cells from selected adult donors FLT3 EMCN CD33 Healthy cell protection HSC aCAR iCAR Host immune cell SENTI-202 Cancer cell killing Blast cell CD33 LSC FLT3 SENTI-202 Gene Circuit Design • 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 • 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-202 is designed to selectively kill both AML blasts and LSCs while protecting healthy HSC/HSPCs using its novel CD33 OR FLT3 NOT EMCN Logic-Gated gene circuit


 
SENTI-202 Scalable Manufacturing Process Off-the-Shelf Allogeneic CAR-NK Lenti virus Outpatient use potential Isolate from selected donors Thaw and Infuse Off-the-Shelf Scalable Process NK Cells Selected Donor Engineer Cryopreserve and Store Expand SENTI-202 Gene Circuit delivered through single transduction step 1 2 3 4 1 Easy to thaw vials Final product harvested and cryopreserved NK cells isolated from peripheral blood of selected donors NK cells efficiently engineered with Gene Circuits High post- thaw potency Gene Circuit Engineered CAR- NK cells Patient 7


 
SENTI-202 Phase 1 Trial (SENTI-202-101) Design A multicenter, multinational, open-label study (NCT06325748) ECOG: European Cooperative Oncology Group; RP2D: recommended phase 2 dose; MTD: Maximum tolerated dose; DLT: dose limiting toxicity; G: Grade by CTCAE v5.0 and other applicable Grading systems; ELN: European LeukemiaNet; CyTOF: Cytometry by Time-of-Flight; BM: bone marrow 1Per WHO 2022 Classification; Key Eligibility Criteria Study Objectives • ≥18 and <75 years • ECOG 0-1 • R/R CD33 and/or FLT3 expressing heme malignancies • CD33+ by local assessment • R/R AML (1-3 prior Rx) • R/R MDS with increased blasts1 (1-2 prior Rx) • Must have received targeted agents if applicable mutations • Primary objective- safety and determination of MTD/RP2D • DLT definition includes: • ≥ G3 non-hematologic toxicities • Prolonged G4 neutropenia /thrombocytopenia not due to underlying disease • Other key objectives • Efficacy based on ELN 2022 criteria (AML) • MRD assessed per local standard of care • Pharmacokinetics (PK) • Pharmacodynamics (PDn) using CyTOF on serial BM samples Study Design Study Dosing “3+3” Dose finding followed by AML, MDS and other expansion cohorts at RP2D 2 Dose Levels and 2 schedules planned Opening dose cohort anticipated to be biologically active 8


 
SENTI-202 Phase 1 Trial (SENTI-202-101) Dosing Schema- Preliminary RP2D Identified 28Day -7 to -3 0 7 14 SENTI-202 Dose Schedule Efficacy Assessment Multiple cycles allowed to achieve optimal response Lymphodepletion Fludarabine/Cytarabine (Ara-C) 28Day -7 to -3 0 3 7 10 14 Dose SCHEDULE I SCHEDULE II SENTI-202 Dose Levels Opening Dose Cohort was Anticipated to be Biologically Active Schedule I Dose Level 1, N = 3 No DLTs Schedule I Dose Level 2, N = 3 No DLTs Identified as preliminary RP2D based on totality of clinical data Schedule II Dose Level 1, N = 3 No DLTs Multi-Dose Cycle Dose Level CAR+ NK Cells/Dose 1 1 x 109 2 1.5 x 109 9


 
preliminary RP2D Study Enrolled a High-Risk R/R AML Population with Multiple Baseline Adverse Characteristics Data from an open clinical database of an ongoing study as of 7 Apr 2025 Baseline Characteristics Dose Level 1 Dose Level 2 All Patients N = 9Schedule I N = 3 Schedule II N = 3 Schedule I N = 3 Age, yr, median (range) 64 (26,72) 41 (36, 67) 63 (51, 69) 63 (26, 72) Male, n (%) 1 (33) 2 (67) 3 (100) 6 (67) AML, n (%) 3 (100) 3 (100) 3 (100) 9 (100) Years from AML diagnosis, median (range) 2.84 (0.5, 6.2) 0.49 (0.3, 0.8) 0.94 (0.5, 1.0) 0.75 (0.3, 6.2) Adverse risk by ELN 2022, n (%) 2 (67) 2 (67) 3 (100) 7 (78) Baseline bone marrow blasts, %, median (range) 20 (15, 69) 30 (18, 31) 45 (10, 93) 30 (10, 93) Baseline platelet count < 50 x 109/L , n (%) 0 (0) 2 (67) 2 (67) 4 (44) • Median of <1 yr from diagnosis to trial entry across all patients and in preliminary RP2D cohort • Majority of patients (all in preliminary RP2D cohort) with adverse risk genetics by ELN 2022 criteria 10


 
preliminary RP2D Study Subjects had Received Multiple Prior Therapies Data from an open clinical database of an ongoing study as of 7 Apr 2025; * Primary refractory defined as failure to achieve cCR or cCR lasting <3 mo with front-line therapy • Median of 2 lines before study entry overall and in preliminary RP2D cohort • All patients with previous chemotherapy exposure including fludarabine and/or cytarabine (4 received both) and majority with previous venetoclax exposure Prior Therapy Dose Level 1 Dose Level 2 All Patients N = 9Schedule I N = 3 Schedule II N = 3 Schedule I N = 3 Number of prior lines, median (range) 1 (1,1) 2 (1, 2) 2 (2, 3) 2 (1,3) Chemotherapy, n(%) 3 (100) 3 (100) 3 (100) 9 (100) Fludarabine and/or Ara-C, n (%) 3 (100) 3 (100) 3 (100) 9 (100) Anthracycline, n (%) 3 (100) 2 (67) 3 (100) 8 (89) Venetoclax, n (%) 1 (33) 3 (100) 3 (100) 7 (78) Hypo-methylating Agents, n (%) 2 (67) 3 (100) 3 (100) 8 (89) FLT3/IDH2 targeted therapy, n (%) 1 (33) 1 (33) 1 (33) 3 (33) Bone marrow transplant, n (%) 1 (33) 0 (0) 1 (33) 2 (22) Primary refractory*, n (%) 1 (33) 2 (67) 2 (67) 5 (56) 11


 
preliminary RP2D Patients Received a Median of 2 Cycles of SENTI-202 Therapy Data from an open clinical database of an ongoing study as of 7 Apr 2025; cCR: composite CR includes CR, CRh, CRi • Median of 2 cycles across dose cohorts • Majority of patients discontinued SENTI-202 after achieving cCR with none discontinuing due to adverse event Exposure Dose Level 1 Dose Level 2 All Patients N = 9Schedule I N = 3 Schedule II N = 3 Schedule I N = 3 Number of SENTI-202 treatment cycles, median (range) 2 (1, 2) 2 (1, 2) 2 (1, 2) 2 (1, 2) Subjects continuing treatment as of data-cut, n (%) 0 2 (67) 0 2 (22) Subjects discontinuing treatment, n (%) 3 (100) 1 (33) 3 (100) 7 (78) Adverse Event 0 0 0 0 Achieved Optimal Response (cCR) 2 (67) 0 2 (67) 4 (44) Disease Progression/ Stable Disease 1 (33) 1 (33) 1 (33) 3 (33) 12


 
preliminary RP2D Preliminary Safety Data Indicate that SENTI-202 is Well Tolerated AEs: treatment emergent adverse events includes adverse events with onset after SENTI-202 dosing and within 30 days of last dose of study treatment; Grading per CTCAE v5.0 Data from an open clinical database of an ongoing study as of 7 Apr 2025 SENTI-202 was well tolerated • In general, G3-4 AEs on study were hematologic, unrelated to SENTI-202 and consistent with R/R AML patients receiving LD • No single type of SAE reported in > 1 patient • No significant difference in AE profile across dose cohorts Any Grade 3-4* AEs Regardless of Relationship Dose Level 1 Dose Level 2 All Patients N = 9Schedule I N = 3 Schedule II N = 3 Schedule I N = 3 Any Grade ≥ 3 AEs, n (%) 3 (100) 3 (100) 3 (100) ^ 9 (100) Febrile Neutropenia 1 (33) 1 (33) 2 (67) ^ 4 (44) Platelet Count Decreased 2 (67) 0 2 (67) ^ 4 (44) Anemia 1 (33) 1 (33) 0 2 (22) Abdominal Pain 1 (33) 1 (33) 0 2 (22) *No Grade 5 AEs, ^ 1 patient with G3 febrile neutropenia and G4 platelet count decreased assessed as possibly related to SENTI-202 13


 
SENTI-202 Related AEIs Were Low Grade and Manageable with Standard of Care AEIs: AEs of Interest; Grading per ASTCT criteria Data from an open clinical database of an ongoing study as of 7 Apr 2025 Patient # (Dose Cohort) Event Term (Grade) Onset from SENTI-202 Dose (days) Duration (days) 001-0004, (1) Chills, G1 0 1 Pyrexia, G1 0 1 008-005, (1) Pyrexia, G1 0 5 Hypotension, G1 3 1 102-007, (prelim. RP2D) Pyrexia, G1 1 1 Hypoxia, G2 1 1 • 3 pts experienced G1 pyrexia with either hypotension or hypoxia in 1 each, typically within 1 day of SENTI-202 dosing that were reported as Cytokine Release Syndrome (CRS) • Events resolved rapidly with standard of care; None were serious • Likely represent delayed infusion reactions described with NK cell therapies • No other AEIs or DLTs reported on study 14


 
preliminary RP2D Responses Observed Across All Dose Cohorts Data from an open clinical database of an ongoing study as of 7 Apr 2025 Best Overall Response on Study, n (%) Dose Level 1 Dose Level 2 All Patients N = 7*Schedule I N = 3 Schedule II N = 1* Schedule I N = 3 Overall Response Rate (ORR) 2 (67) 1 (100) 2 (67) 5 (71) composite CR Rate (cCR)^ 2 (67) 0 2 (67) 4 (57) Negative MRD Status in cCR Patients 2/2 (100) N/A 2/2 (100) 4/4 (100) Response Category, n(%) CR 2 (100) 0 1 (33) 3 (43) CRh 0 0 1 (33) 1 (14) MLFS 0 1 (100) 0 1 (14) SD 0 0 1 (33) 1 (14) PD 1 (33) 0 0 1 (14) *Two patients continuing into second Cycle after achieving SD with blast reduction from 31% to 13% and 5% to 3% respectively are excluded from best overall response assessment; ̂ CR + CRh + CRi AML Response • 5 of 7 patients overall achieved ORR • 2/3 and 4/7 patients achieved cCR respectively in preliminary RP2D cohort and all patients • 4/4 cCR patients were MRD- • All cCR responses are ongoing as of data-cut with median duration of response not reached 15


 
Rapid Bone-Marrow Blast Reduction Observed Across All Dose Cohorts Data from an open clinical database of an ongoing study as of 7 Apr 2025 Blast Reduction Noted in Majority of Patients Across All Dose Cohorts 16 * End of cycle 1 for patients 8 and 9


 
Early Deep Responses Noted Across Dose Levels with Durability 8+ Months I0 Ref: Primary refractory defined as failure to achieve cCR or cCR lasting <3 mo with front-line therapy; Adv. Risk: Adverse Risk genetics by ELN 2022; FA Exp: fludarabine and/or Ara-C Exposed, both indicates exposed to both agents; FA Ref: Fludarabine and/or Ara-C refractory (failure to achieve cCR or cCR lasting < 3 mo), both indicates refractory to both agents; #Patient had detectable IDH2 mutation by NGS while in morphologic remission and started on venetoclax/enasidenib; Data from an open clinical database of an ongoing study as of 7 Apr 2025 pr el im in ar y RP 2D 0 30 60 90 120 150 180 210 CR MRD-* CR MRD+# 5+ mo. CR CRh MRD+* CRh MRD-* HCT 4+ mo. CR SD No response ^Cycle1 ^^ Cycle 2 ^ ^^ ^ Days 0 30 60 90 120 150 180 210 240 270 300 330 360 SD SD PR CR MRD-** HCT 8+ mo. CR CR MRD-* HCT 7+ mo. CR PD Death MLFS MRD+* PD ^ Cycle 1 ^^ Cycle 2 ^ ^^ ^ ^^ ^ ^^ ^ ^ Days *MRD by multi-parametric flow (sensitivity ≤ 1/10-4), **MRD by NGS (sensitivity ≤ 1/10-2) Pt I0 Ref Adv. Risk FA Exp FA Ref Pt1 No Yes Yes No Pt2 No No Yes No Pt3 Yes Yes Yes Yes Pt7 Yes No Yes- both Yes- both Pt8 Yes Yes Yes Yes Pt9 Unk Yes Yes- both Unk Pt I0 Ref Adv. Risk FA Exp FA Ref Pt4 Yes Yes Yes- both Yes- both Pt5 No Yes Yes- both No Pt6 Yes Yes Yes Yes 17


 
CyTOF Bone Marrow Data Reveals SENTI-202 Treatment Resulted in Decreased LSCs in Responders IdU: 5-Iodo-2’-Deoxyuridine; Data from an open clinical database of an ongoing study as of 7 Apr 2025 LSC (CD34+ CD38low) in Bone Marrow % C D 34 + C D 38 lo w LS C o f A M L ce lls LSCs in bone marrow at baseline are largely non-cycling when analyzed by Ki67 and IdU • CyTOF measured 49 different proteins in serial bone marrow derived mononuclear cells samples from baseline and end of each Cycle • At baseline, majority of leukemic stem cells (LSCs) were in G0 phase and not expected to be susceptible to chemotherapy • With SENTI-202 treatment, LSCs decreased > 10-fold in all patients who achieved cCR 18 * Subject 5 samples had low viability * 100 10 1 0.1 0.01 0 Baseline C1D28 C2D28


 
Rapid Normalization of Peripheral Blood Cell Count along with Protection of BM HSPCs in Patients who Achieved cCR Data from an open clinical database of an ongoing study as of 7 Apr 2025 Peripheral Blood Cell Counts Rapid blood cell count recovery in periphery in patients who achieved cCR • Median of 21 days for neutrophil count ≥ 0.5 and 1 x109/ L, and 28/35 days to platelet count ≥ 50 and 100 x109/ L • CyTOF analyses revealed HSPCs were maintained or increased in bone marrow of patients who achieved cCR consistent with SENTI-202 Logic Gate mechanism of action HSPC (CD34+ CD38low) in Bone Marrow (BM) % C D 34 + C D 38 lo w H SP C of a ll ce lls 0 0.5 1 1.5 2 2.5 0 50 100 150 200 250 -7 0 7 14 21 28 Ab so lu te N eu tr op hi l C ou nt (x 1 09 / L ) Pl at el et C ou nt (x 1 09 / L ) Days 19 0.001 0.1 1 10 0.01 100 Baseline C1D28 C2D28 * * Patient 5 samples had low viability.


 
SENTI-202 Is Detected in Periphery of All Treated Patients Consistent with Allo-NK Profile Interim PK data as of 7 Apr 2025; value of 1 assigned for timepoints with non-measurable transgene, LLOQ estimated using equivalent DNA loading and is the lower limit of quantitation • PK profile consistent with allogeneic NK cell therapy • Modest peripheral expansion in first 14 days consistent with NK biology and safety of SENTI-202 • Clearance >14 days from periphery • No significant difference in exposure across patients who achieved cCR or not • No significant difference in exposure across Dose Cohorts • No significant difference in exposure between Cycle 1 and 2 Cycle 1 LLOQC op ie s/ μg D N A Time (Days) 0 100 1000 10,000 7 14 21 28 0 100 1000 7 14 21 28 LLOQ 10,000 Cycle 2 20


 
Dosing and Safety Conclusions- SENTI-202 Generally Well Tolerated in R/R AML Patients • SENTI-202 is a First-In-Class Off-the-Shelf Logic Gated selective CD33 OR FLT3 NOT EMCN CAR NK cell therapy • Designed to selectively kill both AML blasts and LSCs while protecting healthy HSPCs with a novel OR/NOT logic gate gene circuit • SENTI-202-101 trial enrolled heavily treated R/R AML patients with poor prognosis • SENTI-202 is well tolerated • Most frequent Grade 3+ AEs were hematologic and consistent with R/R AML patients receiving LD • MTD not reached and preliminary RP2D identified as 1.5B cells/ dose x 3 weekly doses/ 28 days 21


 
Efficacy Conclusions- Promising Preliminary Efficacy Noted with SENTI-202 in R/R AML Patients • Efficacy • 5/7 ORR and 4/7 cCR across all patients including 2/3 cCR in preliminary RP2D cohort • 4/4 cCR MRD- as assessed per local standard of care • All cCR patients maintaining morphologic remission with longest follow up of 8+ mo • PK • SENTI-202 detected in all treated patients, consistent with other allogeneic CAR NK cell therapy PK profiles and its well tolerated safety profile • CyTOF analyses of BM • SENTI-202 treatment decreased LSC frequencies and maintained (or increased) healthy HSPC frequencies in patients achieving cCR consistent with SENTI-202 Logic Gated gene circuit design 22


 
Also at AACR… 23 • First-In-Human, Multicenter Study of SENTI-202, a CD33/FLT3 Selective Off-the-Shelf Logic Gated CAR NK Cell Therapy in Hematologic Malignancies including AML: Correlative Data (#10977) Session: PO.CT01.02 - First-in-Human Phase I Clinical Trials 2 Location: Section 48, #9 Time: 4/29/2025 9:00:00 - 12:00:00 PM • SENTI-202 CD33 OR FLT3 NOT EMCN Logic-Gated Gene Circuit Components Selectively Target AML while Protecting Human HSC/HPCs from Off-Tumor Toxicity in a Humanized Mouse Model (#6833) Session: PO.IM01.17 - Novel In Vivo, In Vitro, and In Silico Models Location: Section 38, #18; Time: 4/30/2025 9:00:00 - 12:00:00 PM


 
Acknowledgements • We deeply appreciate our Patients and their caregivers • Clinical and research staff at all participating Institutions • United States: o SCRI at TriStar Centennial, Nashville, TN o Colorado Blood Cancer Institute, Denver CO o Methodist Physician Practices, PLLC, San Antonio o The University of Texas M.D. Anderson Cancer Center, Houston, TX o UCLA Department of Medicine, Los Angeles, CA • Australia: o Peter MacCallum Cancer Center, Melbourne, Australia • California Institute of Regenerative Medicine (CIRM) for partially funding the study 24


 
Q&A 25


 
EX-99.2 3 ex992_snti2025clinicaldata.htm EX-99.2 Document
senti_logoxpra.jpg
Exhibit 99.2

Senti Bio’s SENTI-202, a First-in-Class Off-the-Shelf Logic Gated Selective CD33 OR FLT3 NOT EMCN CAR NK Cell Therapy, Demonstrates Positive Preliminary Clinical Results in the Treatment of Patients with Relapsed/Refractory AML
Data presented at the American Association for Cancer Research (AACR) Annual Meeting 2025
Dose Finding completed with no dose limiting toxicities and preliminary recommended Phase 2 dose (RP2D) identified
5 of 7 best overall response evaluable patients achieved ORR (3 CR, 1 CRh and 1 morphologic leukemia-free state) across all dose cohorts, including 1 CR and 1 CRh in 3 patients in preliminary RP2D cohort
4 of 4 cCR patients were measurable residual disease (MRD) negative as assessed by local standard of care
Early deep responses with SENTI-202 noted across dose levels with all cCRs ongoing as of the data cut and longest durability of 8+ months
Company to host webcast to discuss the new Phase 1 SENTI-202 data today, April 28th at 8:30 AM ET; Register Here (https://event.choruscall.com/mediaframe/webcast.html?webcastid=TKqN16X9)
Announces certain preliminary first quarter 2025 financial results and provides pipeline update
SOUTH SAN FRANCISCO, Calif., April 28, 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 reported additional positive preliminary data from a Phase 1 clinical trial of SENTI-202, a potential first-in-class off-the-shelf Logic Gated selective CD33 OR FLT3 NOT EMCN chimeric antigen receptor natural killer (CAR-NK) investigational cell therapy, for the treatment of relapsed/refractory (R/R) hematologic malignancies including acute myeloid leukemia (“AML”). As previously announced, the Company will host a conference call and webcast (https://event.choruscall.com/mediaframe/webcast.html?webcastid=TKqN16X9) to discuss the presented data today, April 28, 2025, at 8:30 AM ET (details below).
SENTI-202 CLINICAL DATA UPDATE
The positive preliminary SENTI-202 clinical data was presented on April 27 in a Clinical Trials Oral Minisymposium at the American Association for Cancer Research (AACR) Annual Meeting 2025 (https://www.aacr.org/meeting/aacr-annual-meeting-2025/) in an abstract titled, “First-in-human, multicenter study of SENTI-202, a CD33/FLT3 selective off-the-shelf logic gated CAR NK cell therapy in hematologic malignancies including AML: Clinical data.”(https://www.abstractsonline.com/pp8/#!/20273/presentation/11033)




Timothy Lu, MD, PhD, Co-Founder and CEO of Senti Biosciences commented, “Senti was founded on engineering Logic Gated cell therapies with the enhanced ability to selectively kill cancer cells and protect healthy cells for cancer indications not addressable by existing drugs. Building upon these exciting results, we are continuing to prioritize development of our Logic Gating programs, including SENTI-202 and additional discovery efforts for solid tumors.”
SENTI-202 Clinical Results Summary
•As presented at AACR, 9 patients with relapsed or refractory AML have been treated with various doses of SENTI-202 in the dose finding part of the study and 7 were evaluable for overall response at the data cut-off.
•The Phase 1 study evaluated two dose levels (1 or 1.5 x 109 CAR NK cells/ dose) and two schedules (3 or 5 doses) of SENTI-202 administered every 28 days on Days 0,7,14 or Days 0,3,7,10,14, respectively, following lymphodepletion with fludarabine/Ara-C.
•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.
•Efficacy
•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 the longest follow up being 8+ months, and 3 patients received a bone marrow transplant after treatment with SENTI-202.
•Pharmacokinetics (PK)
•SENTI-202 was detected in all treated patients, consistent with other allogeneic CAR NK cell therapy PK profiles, namely with modest expansion in the first 14 days in the periphery followed by clearance from peripheral blood.
•Bone marrow Cytometry by Time of Flight (CyTOF) analyses




•SENTI-202 treatment decreased AML blasts and leukemia stem cell (LSC) frequencies and maintained (or increased) healthy hematopoietic stem and progenitor cell (HSPC) frequencies in patients achieving cCR, consistent with the SENTI-202 Logic Gated gene circuit’s designed mechanism of action.
•Safety
•SENTI-202 is generally well tolerated with an adverse event profile that is consistent with other investigational NK cell therapies (and patients with underlying AML receiving lymphodepleting chemotherapy. In terms of Grade 3 or higher events in >1 patient on trial, four patients each reported grade 3 or higher febrile neutropenia and decreased platelet count, and two patients each reported grade 3 anemia and abdominal pain, but these side effects were either deemed unrelated to SENTI-202 or resulting from the lymphodepleting chemotherapy in all patients except one. No grade 5 adverse events were observed.
The Phase 1 study of SENTI-202 is continuing to enroll to confirm the preliminary RP2D followed by disease specific expansion cohorts. The trial is funded in part by a grant from the California Institute for Regenerative Medicine.
Kanya Rajangam, MD, PhD, President, Head of R&D and Chief Medical Officer of Senti Bio summarized, “Based on our clinical, correlative and preclinical data, we believe SENTI-202 has the potential to provide a safe and effective treatment option for AML. We remain focused on the successful execution of the study and look forward to further exploring SENTI-202’s potential.”
Stephen A. Strickland, Jr., MD, MSCI, Director, Leukemia Research for Sarah Cannon Research Institute, and the lead author for the AACR abstract, added, “While preliminary, the results demonstrated by SENTI-202 to date continue to be encouraging. There remains a significant unmet medical need in AML for treatments that can overcome tumor heterogeneity and spare healthy cells. Early results are encouraging, not only for the deep durable complete remissions, but also for the excellent safety profile noted thus far. I look forward to seeing additional data and exploring the potential of SENTI-202 to provide a much-needed treatment option to people living with AML.”
ADDITIONAL DATA TO BE PRESENTED
In addition to the Oral Minisymposium, Senti will be presenting data on SENTI-202 in two additional posters during the AACR meeting.
1.Title: First-in-human, multicenter study of SENTI-202, a CD33/FLT3 selective off-the-shelf logic gated CAR NK cell therapy in hematologic malignancies including AML: Correlative data (https://www.abstractsonline.com/pp8/#!/20273/presentation/10464)
Session Type: Poster Session Session Title: PO.CT01.02 - First-in-Human Phase I Clinical Trials 2




Date and Time: Tuesday, April 29, 2025 from 9:00 AM- 12:00 PM CST
Location: Section 48 Abstract Number: CT143 / 9

2.Title: SENTI-202 CD33 OR FLT3 NOT EMCN logic-gated gene circuit components selectively target AML while protecting human HSC/HPCs from off-tumor toxicity in a humanized mouse model (https://www.abstractsonline.com/pp8/#!/20273/presentation/8279)
Session Type:
Poster Session Session
Title: PO.IM01.17 - Novel In Vivo, In Vitro, and In Silico Models
Date and Time: Wednesday, April 30, 2025 from 9:00 AM - 12:00 PM CT
Location: Section 38 Abstract Number: 7271 / 18
CONFERENCE CALL AND WEBCAST DETAILS
Senti Bio management will host a conference call and webcast (https://event.choruscall.com/mediaframe/webcast.html?webcastid=TKqN16X9) for investors, analysts and other interested parties to discuss the data presented at AACR today, April 28, 2025, at 8:30 AM ET.
Interested participants may access the call by dialing (877) 524-8416 (Domestic) +1 (412) 902-1028 (International). The webcast (https://event.choruscall.com/mediaframe/webcast.html?webcastid=TKqN16X9) will be accessible on the Events (https://investors.sentibio.com/events-presentations) page under the Investors section of the Company’s website (www.sentibio.com), and will be archived for 90 days.
FIRST QUARTER PRELIMINARY FINANCIAL HIGHLIGHTS
•Senti Bio also announced certain preliminary, unaudited financial results for the first quarter of 2025. These preliminary financial results are subject to change. Final unaudited financial results will be available upon the filing of the Company’s Quarterly Report on Form 10-Q with the Securities and Exchange Commission on or about May 6, 2025.
•Cash and Cash Equivalents: As of March 31, 2025, Senti Bio held cash and cash equivalents of approximately $33.8 million.
•R&D Expenses: Research and development expenses were $9.3 million and $8.8 million for the three months ended March 31, 2025 and 2024, respectively. The increase of $0.5 million was primarily due to an increase of $1.4 million in external services and supplies cost, offset by a decrease of $0.8 million in personnel-related expenses, including stock-based compensation and $0.2 million in facilities and other cost.




•G&A Expenses: General and administrative expenses were $7.1 million and $7.5 million for the three months ended March 31, 2025 and 2024, respectively. The decrease of $0.4 million was primarily due to a decrease of $0.9 million in personnel-related expenses offset by an increase of $0.5 million in external services and supplies cost.
•Net Loss: Net loss was $14.1 million, or $1.41 per basic and diluted share, for the quarter ended March 31, 2025.

ADDITIONAL PIPELINE UPDATE
SENTI-301A for HCC: As previously announced, Senti Bio has collaborated with Celest Therapeutics (Shanghai) Co. Ltd. (Celest) to evaluate SN301A in a single center Investigator Sponsored Trial in China. SN301A is a Celest product which incorporates Senti’s SENTI-301A gene circuit into Celest’s CAR-NK cells, which are made using Celest’s manufacturing platform in China, which is distinct from Senti Bio’s manufacturing process. Based on the observation of certain dose limiting toxicities in the SN301A Investigator Sponsored Trial, enrollment has been stopped. Senti is evaluating next steps with SENTI-301A/SN301A as part of ongoing pipeline prioritization.
About SENTI-202
SENTI-202 is a 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. First, SENTI-202 contains an OR GATE (providing a “kill” signal), which is an activating CAR that recognizes CD33 and/or FLT3. By targeting either or both of these antigens, SENTI-202 is designed to effectively kill both leukemic blasts and leukemia stem cells, which constitute a difficult-to-eradicate reservoir of AML disease. Second, SENTI-202 contains a NOT GATE (providing a “protect” signal), which is an inhibitory CAR that is designed to recognize healthy cells and protect those healthy cells from being killed, even if they were to express CD33 and/or FLT3, thus potentially widening the therapeutic window. Third, SENTI-202 contains calibrated-release IL-15 (providing an “enhance” signal), which is designed to significantly increase cell persistence, expansion and activity of both the CAR-NK cells and host immune cells. The NK cells used to manufacture SENTI-202 are sourced from selected healthy adult donors.. 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 allogeneic off-the-shelf treatment for AML/MDS patients.
Senti Bio has published (https://www.cell.com/cell-reports/fulltext/S2211-1247(24)00473-X) SENTI-202 preclinical data demonstrating the potential of Logic Gated CAR-NK cell therapy for the treatment of AML.




About AML
AML is a cancer of the blood and bone marrow and is the most common type of acute leukemia in adults. It is estimated there were 20,800 new cases of AML in the United States in 2024. 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 R/R AML, there are few treatment options and median overall survival is typically approximately five months.
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 https://www.sentibio.com or follow Senti Bio on X (https://x.com/sentibio)(@SentiBio) and LinkedIn (https://www.linkedin.com/company/senti-biosciences) (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 (https://x.com/sentibio) and LinkedIn (https://www.linkedin.com/company/senti-biosciences). The information that we post on our website or on X (https://x.com/sentibio) or LinkedIn (https://www.linkedin.com/company/senti-biosciences) 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