Promising results from an ongoing Phase I multicenter study of SENTI-202, a first-in-class, CD33 and/or FLT3 & not endomucin (EMCN), selective off-the-shelf logic gated CAR NK cell therapy in adults with Relapsed/Refractory Acute Myeloid Leukemia (R/R AML)

Promising Results from an Ongoing Phase I Multicenter Study of SENTI-202, a First-In-Class, CD33 AND/OR FLT3 & NOT endomucin (EMCN), Selective Off-the-Shelf Logic Gated CAR NK Cell Therapy in Adults with Relapsed/Refractory Acute Myeloid Leukemia (R/R AML) Nosha Farhadfar,1 Stephen Strickland,2 Ashish Bajel,3 Alireza Eghtedar,4 Brian Garrison,5 Rochelle Emery,5 Kanya Rajangam,5 Gary Schiller,6 Farhad Ravandi7 Publication Number: 1044 1Sarah Cannon Transplant & Cellular Therapy at Methodist, San Antonio, TX, United States, 2SCRI at TriStar Centennial, Nashville, TN, United States, 3Peter MacCallum Cancer Centre and The Royal Melbourne Hospital; University of Melbourne, Melbourne, Australia, 4Colorado Blood Cancer Institute, Denver, CO, United States, 5Senti Biosciences, South San Francisco, CA, United States, 6David Geffen School of Medicine at UCLA, Los Angeles, CA, United States, 7The University of Texas M.D. Anderson Cancer Center, Houston, TX, United States High Unmet Need in Patients with R/R AML even with Recently Approved Therapies CR: complete remission; CRh: complete remission with partial hematologic recovery; OS: overall survival; MRD: measurable residual disease; HSCs: hematopoietic stem cells; 1Brandwein AJBR 2020; 2Dohner Blood 2022; 3USPI Idhifa, Rezlidhia, Xospata, Tibsovo, Revuforj, Mylotarg; 4Zeijlemaker Leukemia 2019; 5Innes Blood 2018 Effective Anti-AML Therapies Need To To achieve deep / MRD negative CR Leading to durable remissions / longer survival3,4 Selectively kill AML blasts & LSCs, and spare HSCs To support normal blood cell count recovery Target heterogenous clones / LSCs4 Leading to improved prognosis / longer survival5 R/R AML Patients have Poor Prognosis Novel Effective Therapies with Limited On-Target Off-Tumor Toxicities are Urgently Needed ~28k R/R AML patients in US/EU Current Standard of Care Responses2,3: - CR ~12-25% - CR/CRh ~20-35% Median OS: 5.3 months (95% CI 4.0-7.5)1 5-year OS: 12.6% (95% CI 7.5-21.1) SENTI-202 Gene Circuit Design SENTI-202 is a First-in-Class Off-the-Shelf Logic Gated Selective CD33 OR FLT3 NOT EMCN CAR NK Cell Therapy for Blood Cancers Healthy NK cells from selected adult donors aCAR iCAR SENTI-202 is designed to: a) selectively kill both AML blasts and LSCs, and b) protect healthy HSC/HSPCs; using its novel CD33 OR FLT3 NOT EMCN logic gated gene circuit 1 2 3 4 SENTI-202 CD33/FLT3 OR Gated activating CAR kills AML blasts and LSCs NK cells have inherent clinical anti-AML activity crIL15 enhances both SENTI-202 and local immune cell activation and expansion EMCN NOT Gated inhibitory CAR protects healthy HSC/HSPCs 1 2 3 4 aCAR: activating chimeric antigen receptor; iCAR: inhibitory chimeric antigen receptor LSC: leukemic stem cell; HSC: hematopoietic stem cell; HSPC: hematopoietic stem and progenitor cell SENTI-202 is an Off-the-Shelf Allogeneic CAR-NK Cell Therapy Available On Demand Outpatient use potential Isolate from selected donors Thaw and infuse Scalable ~14 Day Manufacturing Process Selected Donor Engineer Cryopreserve Expand 1 2 3 4 1 Easy to thaw vials Final product harvested and cryopreserved NK cells isolated from peripheral blood of selected adult donors NK cells efficiently engineered with Gene Circuit High post-thaw potency Lent iviru s NK Cells Single transduction step delivers the full Gene Circuit Patient SENTI-202 SENTI-202 Study Dosing 2 DOSE LEVELS and 2 SCHEDULES Starting dose level anticipated to be biologically active SENTI-202-101 is a Multicenter, Multinational, Open-label Phase 1 Trial in Patients with R/R Hematologic Malignancies* Key Eligibility Criteria Key Objectives Primary objective • Safety and determination of MTD/RP2D • Efficacy (expansion cohorts) based on ELN2022 criteria for AML Other key objectives • Measurable residual disease assessed locally • Pharmacokinetics • Pharmacodynamics using CyTOF on serial BM samples Study Design “3 + 3” Dose finding followed by AML, MDS and other disease specific expansion cohorts at RP2D ADULT PATIENTS ≥18 & <75 YEARS ECOG PS 0-1 • R/R CD33 and/or FLT3 expressing hematologic malignancies • CD33+ by local assessment • R/R AML (1-3 prior therapies) • R/R MDS with increased blasts1 (1-2 prior therapies) • Must have received targeted agents if applicable mutations *NCT06325748 ECOG PS: European Cooperative Oncology Group performance status; MTD: maximum tolerated dose; RP2D: recommended phase 2 dose; ELN: European LeukemiaNet; CyTOF: Cytometry by Time-of-Flight; BM: bone marrow; 1Per WHO 2022 Classification Study Treatment Dosing and SENTI-202 RP2D Selection Dose Level 1 2 CAR+ NK Cells/Dose 1 × 109 1.5 × 109 Study Treatment Lymphodepletion Fludarabine 30 mg/m2/ Cytarabine (Ara-C) 2 g/m2 SENTI-202 Day –7 to –3 0 7 14 28 Day –7 to –3 0 3 7 10 14 28 28 Schedule I Efficacy Assessment Up to 4 cycles allowed to achieve optimal response Schedule II Cells Here we present clinical data from 20 R/R AML patients, including 14 at RP2D and 6 at Dose Level 1 9 R/R AML patients (pts) initially enrolled in dose finding 6 pts in Dose Level 1 (3 each in Schedule I and II) 3 pts in Dose Level 2 (all 3 in Schedule I) Dose Finding RP2D Preliminary RP2D determined to be Dose Level 2, Schedule I based on: • No DLTs/ SENTI-202 related SAEs in any patient/ any dose level • Numeric increase in efficacy with • Dose Level 2 compared to Dose Level 1 with ORR of 67% (2/3) vs 50% (3/6) • Schedule I compared to Schedule II with ORR of 67% (4/6) vs 33% (1/3) R/R AML expansion cohort opened after: • RP2D confirmed as Dose Level 2, Schedule 1 with 3 additional R/R AML patients with no DLTs and continued efficacy RP2D: recommended Phase 2 dose ; DLTs: dose limiting toxicities; ORR: overall response rate; SAEs: treatment emergent serious adverse events RP2D Study Enrolled R/R AML Patients with Multiple Baseline Adverse-risk Characteristics and Poor Prognosis Baseline Characteristics 1 x 109 CAR+ NK cells/ dose N=6 1.5 x 109 CAR+ NK cells/ dose N=14 All Patients N=20 Age, yr, median (range) 52.5 (26, 72) 49 (19, 69) 49 (19, 72) Male, n (%) 3 (50) 7 (50) 10 (50) Race, White/ Other, n (%) 5 (83) / 1 (17) 11 (79) / 3 (21) 16 (80) / 4 (20) ECOG PS 0-1, n (%) 5 (83) 13 (93) 18 (90) Adverse risk by ELN 2022 at diagnosis, n (%) 5 (83) 8 (57) 13 (65) Baseline bone marrow blasts, %, median (range) 21.5 (15.1, 69) 45.2 (6, 92.5) 35 (6, 93) Mutational Status at baseline FLT3: ITD/ TKD/ Type Unk mutated, n (%) 0 / 0 / 1 (17) 3 (21) / 0 / 0 3 (15) / 0 / 1 (5) IDH1/ IDH2 mutated, n (%) 0 / 0 0 / 1 (7) 0 / 1 (5) Baseline absolute neutrophil count < 1 x 109/L, n(%) 1 (17) 12 (86) 13 (65) Baseline platelet count < 50 x 109/L, n(%) 2 (33) 11 (79) 13 (65) • Majority of patients had AML with adverse risk genetics by ELN 2022 criteria • RP2D cohort enrolled patients with increased baseline blasts and more patients with baseline thrombocytopenia/ neutropenia Dose Level 1 Dose Level 2/ RP2D ECOG PS: European Cooperative Oncology Group performance status; ELN: European LeukemiaNet; Dose Level 1 patients include 3 each dosed in Schedule I and Schedule II, Dose Level 2 patients were all dosed in Schedule I. Data from an open clinical database of an ongoing study as of 17-Oct-2025 Heavily Pretreated R/R AML Population Including Many Primary Refractory & Refractory to Most Recent Line of Therapy before Study Entry Prior AML Treatments 1 x 109 CAR+ NK cells/ dose N=6 1.5 x 109 CAR+ NK cells/ dose N=14 All Patients N=20 Years from AML diagnosis to study entry, median (range) 0.6 (0.3, 6.1) 0.85 (0.2, 8.6) 0.75 (0.2, 8.6) Number of prior lines, median (range) 1 (1,2) 2 (1,3) 2 (1, 3) Chemotherapy, n (%) 6 (100) 14 (100) 20 (100) Fludarabine and/or Cytarabine, n (%) 6 (100) 14 (100) 20 (100) Cytarabine (Ara-C), n (%) 6 (100) 14 (100) 20 (100) Fludarabine (Flu) , n (%) 2 (33) 5 (36) 7 (35) Anthracycline, n (%) 5 (83) 11 (79) 16 (80) Venetoclax, n (%) 4 (67) 13 (93) 17 (85) Hypomethylating Agents, n (%) 4 (67) 11 (79) 15 (75) FLT3/IDH targeted therapy, n (%) 2 (33)/ 0 3 (21)/ 1 (7) 5 (25)/1 (5) Prior HCT, n (%) 1 (17) 6 (43) 7 (35) Refractory to most recent regimen, n (%) 1 (17) 11 (79) 12 (60) Primary refractory*, n (%) 3 (50) 8 (57) 11 (55) Refractory to Flu and/or Ara-C containing regimen, n (%) 3 (50) 8 (57) 11 (55) • All patients were exposed to chemotherapy • Most patients were exposed to anthracycline, venetoclax & hypomethylating agents • RP2D cohort enrolled patients who were more heavily pre-treated, more prior HCT and more patients refractory to most recent regimen before SENTI-202 compared to Dose Level 1 Dose Level 1 Dose Level 2/ RP2D *Primary refractory defined as failure to achieve complete remission +/- count recovery lasting <3 mo with front-line therapy. Dose Level 1 patients include 3 each dosed in Schedule I and Schedule II, Dose Level 2 patients were all dosed in Schedule I. Data from an open clinical database of an ongoing study as of 17-Oct-2025 Patients Received a Median of 1 Cycle on Treatment Overall and None Discontinued due to an Adverse Event Exposure 1 x 109 CAR+ NK cells/ dose N=6 1.5 x 109 CAR+ NK cells/ dose N=14 All Patients N=20 Number of SENTI-202 treatment cycles, n (%) 1 Cycle 2 (33) 12 (86) 14 (70) 2 Cycles 4 (67) 2 (14) 6 (30) Number of SENTI-202 Cycles, median (range) 2 (1,2) 1 (1,2) 1 (1, 2) Subjects continuing treatment as of data-cut, n (%) 0 4 (29) 4 (20) Subjects discontinuing treatment, n (%) 6 (100) 10 (71) 16 (80) Adverse Event 0 0 0 Dose Level 1 Dose Level 2/ RP2D CR: complete remission, CRh :CR with partial hematologic recovery; MLFS: morphologic leukemia- free state. Dose Level 1 patients include 3 each dosed in Schedule I and Schedule II, Dose Level 2 patients were all dosed in Schedule I. Data from an open clinical database of an ongoing study as of 17-Oct-2025 • In general, RP2D patients achieved a response with 1 Cycle and received a median of 1 Cycle of SENTI-202 compared to Dose Level 1 patients who received a median of 2 Cycles Any Grade 3+ Treatment Emergent Adverse Events (AE) or Serious Adverse Events (SAE) On Study, Regardless of Relationship to SENTI-202 Event Term 1 x 109 CAR+ NK cells/ dose N=6 1.5 x 109 CAR+ NK cells/ dose N=14 All Patients N=20 Any ≥ Grade 3 AE, n (%) regardless of relationship* 6 (100) 12 (86) 18 (90) Febrile Neutropenia 2 (33) 7 (50) 9 (45) Platelet Count Decreased 2 (33) 2 (14) 4 (20) Anemia 2 (33) 1 (7) 3 (15) Thrombocytopenia 1 (17) 2 (14) 3 (15) Pneumonia 0 3 (21) 3 (15) Abdominal Pain 3 (50) 0 3 (15) Hypokalemia 0 2 (14) 2 (10) Hypoxia 1 (17) 1 (7) 2 (10) Sepsis 0 2 (14) 2 (10) *All events are unrelated to SENTI-202 as assessed by the Investigator except for 1 patient with events of both Grade 3 febrile neutropenia and Grade 4 platelet count decreased Event Term 1 x 109 CAR+ NK cells/ dose N=6 1.5 x 109 CAR+ NK cells/ dose N=14 All Patients N=20 Any Grade SAE, n (%) regardless of relationship* 2 (33) 5 (36) 7 (35) Pneumonia 0 2 (14) 2^ (10) Sepsis 0 2 (14) 2^ (10) *All events are unrelated to SENTI-202 as assessed by the Investigator, ^1 patient experienced both events • Grade 3+ AEs or SAEs of any Grade in ≥10% of patients are predominantly hematologic events or pneumonia/sepsis in the setting of neutropenia and consistent with effects of LD chemotherapy in patients with R/R AML • Hematologic events generally resolved rapidly in patients achieving CR/CRh with SENTI-202 Treatment emergent adverse events includes events with onset after SENTI-202 dosing and within 30 days of last dose of study treatment regardless of relationship, and events that are at least possibly related to SENTI-202 with onset date > 30 days after last dose of study treatment. Grading per CTCAE v5.0. Dose Level 1 patients include 3 each dosed in Schedule I and Schedule II, Dose Level 2 patients were all dosed in Schedule I. Data from an open clinical database of an ongoing study as of 17-Oct-2025 Dose Level 1 Dose Level 2/ RP2D Dose Level 1 Dose Level 2/ RP2D SENTI-202 Related AEIs are Predominantly Grade 1/2 Pyrexia Events that are Readily Managed with Standard of Care Grading per ASTCT criteria where applicable; Dose Level 1 patients include 3 each dosed in Schedule I and Schedule II, Dose Level 2 patients were all dosed in Schedule I. * Sample values ULOQ for 2 patients; ^ IL-6 levels referenced from Teachey et al (2016), maximum level observed from adult cohort treated with anti-CD19 CAR-T; Data from an open clinical database of an ongoing study as of 17-Oct-2025 SENTI-202 related AEIs reported in 7/20 (35%) of patients: • Grade 1/2 pyrexia +/- chills, hypotension and/or hypoxia • Majority on day of dosing and resolved rapidly with standard of care • Reported as CRS or IRR and all events non-serious • Consistent with delayed infusion related reactions reported with NK cell therapies • Cytokines, including IL-6, generally not elevated on trial including in patients experiencing any AEI Dose Pt Event Term Grade Onset Day from Most Recent Dose of SENTI-202 Duration of Event AEI Term Serious? / Resolution Dose Level 1 (1 x 109 CAR+ NK cells/ dose) 01-04 Pyrexia Chills 2 1 0 <24 hours CRS No / Resolved with Standard of Care 08-05 Pyrexia Hypotension 1 1 0 3 5 days < 24 hours Dose Level 2 /RP2D (1.5 x 109 CAR+ NK cells/ dose) 12-07 Pyrexia Hypoxia 1 2 1 < 24 hours05-18 Pyrexia Pyrexia Hypotension 1 2 2 2 7 7 05-20 Pyrexia 2 1 12-15 Pyrexia 1 0 < 24 hours IRR 12-22 IRR 1 Max. level in CAR-T B-ALL from literature^ AEI: Treatment Emergent Adverse Event of Interest, Pt: Patient ID, CRS: Cytokine Release Syndrome, IRR: Infusion Related Reaction 50% of Patients Achieved a Response with SENTI-202 Treatment Response 1 x 109 CAR+ NK cells/ dose N=6 1.5 x 109 CAR+ NK cells/ dose N=12 All Patients N=18^ Overall Response Rate (ORR), n (%) 3 (50) 6 (50) 9 (50) CR/CRh rate, n (%) 2 (33) 5 (42) 7 (39) Response Category, n(%) CR 2 (33) 3 (25) 5 (28) CRh 0 2 (17) 2 (11) MLFS 1 (17) 1 (8) 2 (11) Negative MRD* Status, n/n (%) in CR patients 2/2 (100) 3/3 (100) 5/5 (100) in CR/CRh patients 2/2 (100) 4/5 (80) 6/7 (86) in CR/CRh/MLFS patients 2/3 (67) 5/6 (83) 7/9 (78) Median Time to Response (min, max), mo 1.2 (1.1,1.2) 1.2 (1.0,1.3) 1.2 (1.0, 1.3) Median Duration of Follow-Up (min, max) mo 8.0 (3.6, 17.5) 3.1 (0.9, 9.1) 4.8 (0.9, 17.5) ^2 patients early in Cycle 1 and too early to evaluate response as of data cut-off date; *MRD assessed by multi- parametric flow (sensitivity ≤10-4) in all patients except one (assessed by NGS, sensitivity ≤10-2) 50% of patients at RP2D and overall achieved a response • 42% of patients at RP2D and 39% overall achieved a CR/CRh • All CRs and ~80+% of all responses are MRD negative • With limited follow up in RP2D cohort, current Kaplan- Meier estimate of median duration of composite CR across all patients: • 7.6 months (25th and 75th percentile being 6.1, NE) Dose Level 1 Dose Level 2/ RP2D CR: complete remission, CRh :CR with partial hematologic recovery; MLFS: morphologic leukemia- free state; MRD: measurable residual disease; NGS; next-generation sequencing; composite CR includes CR/ CRh and CR with incomplete hematologic recovery; NE: not estimated. Dose Level 1 patients include 3 each dosed in Schedule I and Schedule II, Dose Level 2 patients were all dosed in Schedule I. Data from an open clinical database of an ongoing study as of 17-Oct-2025 SENTI-202 Responses are Durable with Longest Durability > 1 year C1 C2 C1 C2 C1 C2 C1 C1 C1 C1 C1 C1 C1 C2 C1 C2 C1 C2 C1 C1 C1 C1 C1 C1 Post HCT visceral GvHD Tx Tx Tx Tx Tx C1/C2 Cycle 1/2 start EOT End of study treatment Ongoing as of data cut Tx HCT Withdrawal of consent Death Treatment and Follow-up: Best Response to SENTI-202: MRD negative CR CRh SENTI-202 Efficacy: Duration of: composite CR MLFS PR SD PD ‡ Adverse risk genetics ① Primary refractory ② Refractory to Flu and/or Ara-C ③ Refractory to most recent Rx * Dose Level 1 Baseline Poor Prognosis Indicators/ Dose Level: CR: complete remission, CRh :CR with partial hematologic recovery; MLFS: morphologic leukemia- free state; PR: partial remission; SD: stable disease; PD; progressive disease. MRD: measurable residual disease assessed by multi-parametric flow (sensitivity ≤10-4) in all patients except one (assessed by NGS, sensitivity ≤10-2); composite CR includes CR/ CRh and CR with incomplete hematologic recovery; HCT: hematopoietic stem cell transplant; GvHD: graft versus host disease. Pt 07-06 had detectable IDH2 mutation by NGS ~3.5 months prior to morphologic relapse and started on venetoclax/enasidenib. Data from an open clinical database of an ongoing study as of 17-Oct-2025 EOT EOT EOT EOT EOT EOT EOT EOT EOT EOT EOT EOT EOT EOT EOT EOT SENTI-202 Peripheral Blood Exposure is Generally Consistent Across All Dosed Patients • SENTI-202 is detected in periphery of treated subjects, with PK profile consistent with allogeneic NK cell therapies • Peripheral expansion in the first 14 days • Clearance from periphery after the first two weeks • Patients who responded (ORR) had a preliminary trend* to increased SENTI-202 exposure compared to non-responders • Preliminary trend* to dose dependent increased SENTI-202 exposure with increased dose level *statistically not-significant PK: pharmacokinertics; ORR: overall response. Value of 1 assigned for timepoints with non-measurable transgene, LLOQ estimated using equivalent DNA loading and is the lower limit of quantitation; Note: Subject 1 Cycle 1 samples were processed out of stabilit y window and are excluded from analysis of PK parameters Dose Level 1 patients include 3 each dosed in Schedule I and Schedule II, Dose Level 2 patients were all dosed in Schedule I. Interim PK data as of 17-Oct-2025 LLOQ LLOQ SENTI-202 is Well-Tolerated in a Heavily Pretreated R/R AML Population, with Future Out-Patient Dosing Potential • 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 gated gene circuit – Potential to readily combine with standard of care agents in earlier lines of treatment based on novel mechanism of action and differentiated safety profile • SENTI-202-101 trial has enrolled heavily pretreated R/R AML patients with poor prognosis – Dose finding is complete with no DLTs/ MTD and RP2D confirmed – Dose expansion is ongoing at RP2D of 1.5 x 109 CAR+ NK cells/ dose X 3 weekly doses/ 28 days • SENTI-202 is well tolerated with out-patient dosing potential – Most frequent Grade 3+ AEs were predominantly hematologic, unrelated to SENTI -202 and consistent with events observed in R/R AML patients receiving LD – No SENTI-202 related SAEs/ Dose Limiting Toxicities/ AEs resulting in discontinuation – Most frequent SENTI-202 related AEIs: Grade 1/2 pyrexia that resolves rapidly with standard of care SENTI-202 Achieved a High Rate of Deep, Durable, MRD-Negative Responses • SENTI-202 demonstrates promising preliminary efficacy – 50% of patients at RP2D and 50% of patients overall achieved an ORR – 42% of patients at RP2D and 39% of patients overall achieved CR/CRh – Estimated median duration of composite complete remission across all patients of 7.6 months (6.1, NE) – 100% CR and ~80+% of all responses are MRD negative • SENTI-202 peripheral PK consistent with allogeneic CAR NK cell therapy profiles – Preliminary trend to dose dependent increased exposure observed at RP2D and in patients achieving an ORR SENTI-202 dose expansion is ongoing to further evaluate efficacy and safety in patients with R/R AML Also at ASH… Correlative Data from an Ongoing Phase 1, Multicenter Study of SENTI-202, a First-in-Class, CD33 OR FLT3 & NOT Endomucin (EMCN), Selective Off-the-Shelf CAR NK Cell Therapy for Acute Myeloid Leukemia (AML) is Consistent with SENTI-202's Clinical Activity and Unique Logic Gated Mechanism of Action • Session Name: 704. Cellular Immunotherapies: Early Phase Clinical Trials and Toxicities: Poster III Session Date: Today, December 8, 2025 Session Time: 6:00 PM - 8:00 PM Presentation Time: 6:00 PM - 8:00 PM Room: OCCC - West Halls B3-B4 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 • Senti Biosciences, our Sponsor and the developer of SENTI-202 o Amy Alford, Maria Garcia, Nelia Leemans, Enping Hong o Faraz Siddiqui, Kerry Joshi, Andrew Lee and the rest of the technical operations & quality teams • California Institute of Regenerative Medicine (CIRM) for partially funding the study

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