EX-99.2 3 ex992.htm EX-99.2 ex992
NASDAQ: SNTI | sentibio.com SENTI-202-101 Promising Results in the Treatment of Relapsed/Refractory Acute Myeloid Leukemia (R/R AML) in Ongoing Phase 1 Trial (SENTI-202-101) December 9, 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. 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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


 
3 Tim Lu, MD, PhD CEO and Co-Founder Kanya Rajangam, MD, PhD President, Head of R&D and CMO Nosha Farhadfar, MD Hematologist and Bone Marrow Transplant Physician


 
Tim Lu, MD, PhD CEO and Co-Founder 4


 
Pipeline of Best-in-Class Logic Gated Cell Therapies 5 Enable CAR-NK / CAR-T Cells to Address Blockbuster Liquid and Solid Tumors *ADC: antibody drug conjugate; TCE: T cell engagers Healthy CellsCancer Cells KILLKILL Recognize Single Antigen Target Single Antigen Target may be found on both cancer and healthy cells Commercially approved CAR T cell therapies Biologics (ADC/TCE)* Non-Logic Gate Approaches Senti Bio’s Logic Gate Approach Healthy CellsCancer Cells PROTECT (DO NOT KILL) KILL SENTI-202 and Other Undisclosed Programs OR Gate (aCAR) e.g., Kill if you see Antigens CD33 or FLT3 NOT Gate (iCAR) e.g., Do Not Kill if you see Antigen EMCN even if you see CD33 or FLT3 Recognizes Multiple Antigen Targets


 
First-in-Class Off-the-Shelf Logic-Gated Selective CD33 OR FLT3 NOT EMCN CAR NK Cell Therapy Investment from Leading Healthcare Institutional Investors Lead Program SENTI-202 Investment Highlights 6 *CR: Complete Remission; CRh: CR with partial hematologic recovery; cCR: composite Complete Remission; MRD: Measurable Residual Disease; AML: Acute Myeloid Leukemia  Clinical Proof of Concept further validated with 20 Relapsed Refractory (R/R) AML patients treated in ongoing multinational, multicenter Phase 1 trial  Recommended Phase 2 Dose confirmed  Durable responses with 50% ORR and 42% CR/CRh rates at RP2D, 7.6mo estimated median duration of cCR overall  High MRD-negative rates (e.g., 100% CRs MRD-)  Excellent safety profile, outpatient dosing potential  Confirmed Mechanism of Action of selective killing of AML blasts and leukemic stem cells, with sparing of healthy bone marrow stem cells  FDA Regenerative Medicine Advanced Therapy (RMAT) Designation and Orphan Drug Designation (ODD)  Next steps: Launch pivotal trial & expand into other indications (e.g., Newly Diagnosed AML) in 2026  Validated Logic Gate technology can be expanded into other modalities (e.g., T, in vivo CAR) for additional cancers


 
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 7 LSC: Leukemic stem cells; HSC: hematopoietic stem cell; HSPC: hematopoietic stem and progenitor cell 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 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 • NK cells have inherent clinical anti-AML activity 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 is an Off-the-Shelf Allogeneic CAR-NK Cell Therapy Available On-Demand 8 Lenti virus Outpatient use potential Isolate From Selected Donors Thaw and Infuse Scalable ~14 Day Manufacturing Process NK Cells Selected Donors Engineer CryopreserveExpand SENTI-202 Single transduction step delivers the full Gene Circuit 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 Circuits High post- thaw potency Patient aCAR iCAR SENTI-202 SENTI-202


 
9 NDAML estimates per Wall Street research; R/R AML estimates assume 60% of new AML cases become relapsed/refractory ~12K ~21K ~16K ~26K 0 5,000 10,000 15,000 20,000 25,000 30,000 35,000 40,000 45,000 50,000 R/R AML NDAML US EU ~28k ~47k Relapsed/Refractory AML Newly Diagnosed AML SENTI-202 Has the Potential to Address Major Unmet Needs in AML, a Multi-Billion Dollar Market Opportunity


 
Nosha Farhadfar, MD Hematologist and Bone Marrow Transplant Physician 10


 
High Unmet Need in Patients with R/R AML Even With Recently Approved Therapies HCT: Hematopoietic cell transplantation; CR: complete remission; CRh: complete remission with partial hematologic recovery; OS: overall survival 1: Dohner Blood 2022; 2: USPI Idhifa, Rezlidhia, Xospata, Tibsovo, Revuforj, Mylotarg, Komzifti; 3: Brandwein AJBR 2020; R/R AML Patients Have Poor Prognosis • Current standard of care responses1,2 • CR rate ~12-25% • CR/CRh rate ~20-35% • Median OS: 5.3 months (95% CI 4.0-7.5)3 • 5-year OS: 12.6% (95% CI 7.5-21.1) R/R AML Treatment 1. Eligible for clinical trial? Yes, first priority 2. Eligible for allogeneic HCT? Yes No Mutation-agnostic therapies Step 1* • Salvage chemotherapy +/- venetoclax Targeted therapies Mutation-agnostic therapies Step 1 • FLT3 mutated: Gilteritinib • IDH1 mutated: Ivosidenib#, Olutasidenib# • IDH2 mutated: Enasidenib# • NPM1 mutated: Revumenib#, Ziftomenib#^ • KMT2A translocation: Revumenib#^ Step 1 No standard therapy • Clinical trials best choice • Change agents • Best supportive care Step 2: Allogeneic HCT¶ Step 3: Consider maintenance therapy If no allogeneic HCT, continue treatment * Some patients might go directly to allogeneic HCT or receive lower intensity regimens ¶ Consider DLIs for relapse post HCT, second HCT only indicated in selected patients #Approved by FDA but not EMA for R/R AML pts Adapted from Thol et al. 2024 with updates to include menin inhibitors^ 11


 
AML Response Categories and Clinical Benefit Peripheral Blood CountsAML Blasts ANC ≥ 1.0 x 109/L and PLT ≥ 100 x 109/L Bone marrow blasts <5% and Absence of circulating blasts and Absence of extramedullary disease When assessed for measurable residual disease or MRD (e.g., by MFC, sensitivity of ≤10-4), responses can be without MRD (MRD-) or MRD+ Complete Remission (CR) ANC ≥ 0.5 x 109/L and PLT ≥ 50 x 109/L CR with partial hematologic recovery (CRh) Residual neutropenia (ANC < 1.0 x 109/L) or Residual thrombocytopenia (PLT < 100 x 109/L) CR with incomplete hematologic recovery (CRi) No count recoveryMorphologic Leukemia- Free State (MLFS) MFC: Multiparameter flow cytometry; ANC: Absolute Neutrophil Count; PLT: Platelet Count 12 Achieving response correlates with clinical benefit especially when • CR/CRh • MRD- • Able to be consolidated with allogeneic HCT which is best chance of cure for R/R AML patients Current available therapies limited by • Low CR/CRh/MRD rates, • Significant myelotoxicity and other vital organ toxicities (e.g. cardiac, hepatic, differentiation syndrome) Novel Effective Therapies With Limited On-Target Off-Tumor Toxicities are Urgently Needed HCT: Hematopoietic cell transplantation; cRC: CR + CRh + CRi Dohner Blood 2022


 
How SENTI-202 Could Fit Into the Evolving AML Treatment Landscape 13 • Targets LSCs while sparing healthy HSPCs • Potential to deliver deep, durable MRD- responses • Potential to be stand-alone therapy in patients not eligible for HCT • Safety profile allows use before or after targeted therapies  Novel and Differentiated Mechanism of Action  Phase 1 Clinical Data Shows Excellent Efficacy and Safety Consistent with MoA  Broader Patient Reach  Opportunity to Expand Beyond R/R AML Key Results from 20 Patient R/R AML trial indicate Excellent Efficacy and Safety Profile: ~40% CR/CRh, 100% CR MRD-, median duration 7+ mo, Transient Grade 1/2 pyrexia most common related AE • Not mutation-restricted; fits most R/R AML patients • Favorable safety supports outpatient use • Rapid responses within 1–2 cycles reduces need for long-term treatment • Well-tolerated profile supports combination with frontline standard of care • Opportunity to expand to pediatric AML and higher-risk MDS LSCs: Leukemic stem cells; HSPCs: Hematopoietic stem and progenitor cells


 
Kanya Rajangam, MD, PhD President, Head of R&D and CMO 14


 
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 “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 Design Study Dosing 15


 
1 R P 2D Study Treatment Dosing and SENTI-202 RP2D Selection 21Dose Level 1.5 × 1091 × 109CAR+ NK Cells/Dose 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 R P 2D RP2D: recommended Phase 2 dose ; DLTs: dose limiting toxicities; ORR: overall response rate; SAEs: treatment emergent serious adverse events. Data from an open clinical database of an ongoing study as of 17-Oct-2025 28Day -7 to -3 0 7 14 SENTI-202 Efficacy Assessment Up to 4 cycles allowed to achieve optimal response Study Treatment Lymphodepletion Fludarabine 30 mg/m2/ Cytarabine (Ara-C) 2 g/m2 28Day -7 to -3 0 3 7 10 14 Cells Schedule I Schedule II 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 16


 
Study Enrolled R/R AML Patients with Multiple Baseline Adverse-risk Characteristics and Poor Prognosis Dose Level 2/RP2DDose Level 1 All Patients N=20 1.5 x 109 CAR+ NK cells/ dose N=14 1 x 109 CAR+ NK cells/ dose N=6 Baseline Characteristics 49 (19, 72)49 (19, 69)52.5 (26, 72)Age, yr, median (range) 10 (50)7 (50)3 (50)Male, n (%) 16 (80) / 4 (20)11 (79) / 3 (21)5 (83) / 1 (17)Race, White/ Other, n (%) 18 (90)13 (93)5 (83)ECOG PS 0-1, n (%) 13 (65)8 (57)5 (83)Adverse risk by ELN 2022 at diagnosis, n (%) 35 (6, 93)45.2 (6, 92.5)21.5 (15.1, 69)Baseline bone marrow blasts, %, median (range) Mutational Status at baseline 3 (15) / 0 / 1 (5)3 (21) / 0 / 00 / 0 / 1 (17)FLT3: ITD/ TKD/ Type Unk mutated, n (%) 0 / 1 (5)0 / 1 (7)0 / 0IDH1/ IDH2 mutated, n (%) 13 (65)12 (86)1 (17)Baseline absolute neutrophil count < 1 x 109/L, n(%) 13 (65)11 (79)2 (33)Baseline platelet count < 50 x 109/L, n(%) 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 • 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 17


 
Heavily Pretreated R/R AML Population Including Many Primary Refractory & Refractory to Most Recent Line of Therapy Before Study Entry Dose Level 2/ RP2DDose Level 1 All Patients N=20 1.5 x 109 CAR+ NK cells/ dose N=14 1 x 109 CAR+ NK cells/ dose N=6 Prior AML Treatments 0.75 (0.2, 8.6)0.85 (0.2, 8.6)0.6 (0.3, 6.1)Years from AML diagnosis to study entry, median (range) 2 (1, 3)2 (1,3)1 (1,2)Number of prior lines, median (range) 20 (100)14 (100)6 (100)Chemotherapy, n (%) 20 (100)14 (100)6 (100)Fludarabine and/or Cytarabine, n (%) 20 (100)14 (100)6 (100)Cytarabine (Ara-C), n (%) 7 (35)5 (36)2 (33)Fludarabine (Flu) , n (%) 16 (80)11 (79)5 (83)Anthracycline, n (%) 17 (85)13 (93)4 (67)Venetoclax, n (%) 15 (75)11 (79)4 (67)Hypomethylating Agents, n (%) 5 (25)/1 (5)3 (21)/ 1 (7)2 (33)/ 0FLT3/IDH targeted therapy, n (%) 7 (35)6 (43)1 (17)Prior HCT, n (%) 12 (60)11 (79)1 (17)Refractory to most recent regimen, n (%) 11 (55)8 (57)3 (50)Primary refractory*, n (%) 11 (55)8 (57)3 (50)Refractory to Flu and/or Ara-C containing regimen, n (%) *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 • 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 18


 
Patients Received a Median of 1 Cycle on Treatment Overall and None Discontinued Due to an Adverse Event Dose Level 2/ RP2DDose Level 1 All Patients N=20 1.5 x 109 CAR+ NK cells/ dose N=14 1 x 109 CAR+ NK cells/ dose N=6 Exposure Number of SENTI-202 treatment cycles, n (%) 14 (70)12 (86)2 (33)1 Cycle 6 (30)2 (14)4 (67)2 Cycles 1 (1, 2)1 (1,2)2 (1,2)Number of SENTI-202 Cycles, median (range) 4 (20)4 (29)0Subjects continuing treatment as of data-cut, n (%) 16 (80)10 (71)6 (100)Subjects discontinuing treatment, n (%) 000Adverse Event 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 19


 
Any Grade 3+ Treatment Emergent Adverse Events (AE) or Serious Adverse Events (SAE) On Study, Regardless of Relationship to SENTI-202 Dose Level 2/ RP2DDose Level 1 All Patients N=20 1.5 x 109 CAR+ NK cells/ dose N=14 1 x 109 CAR+ NK cells/ dose N=6 Event Term 18 (90)12 (86)6 (100) Any ≥ Grade 3 AE, n (%) regardless of relationship* 9 (45)7 (50)2 (33)Febrile Neutropenia 4 (20)2 (14)2 (33)Platelet Count Decreased 3 (15)1 (7)2 (33)Anemia 3 (15)2 (14)1 (17)Thrombocytopenia 3 (15)3 (21)0Pneumonia 3 (15)03 (50)Abdominal Pain 2 (10)2 (14)0Hypokalemia 2 (10)1 (7)1 (17)Hypoxia 2 (10)2 (14)0Sepsis *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 Dose Level 2/ RP2DDose Level 1 All Patients N=20 1.5 x 109 CAR+ NK cells/ dose N=14 1 x 109 CAR+ NK cells/ dose N=6 Event Term 7 (35)5 (36)2 (33) Any Grade SAE, n (%) regardless of relationship* 2^ (10)2 (14)0Pneumonia 2^ (10)2 (14)0Sepsis *All events are unrelated to SENTI-202 as assessed by the Investigator, ^1 patient experienced both events 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 • 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 20


 
SENTI-202 Related AEIs are Predominantly Grade 1/2 Pyrexia Events That are Readily Managed with Standard of Care Serious? / Resolution AEI Term Duration of Event Onset Day from Most Recent Dose of SENTI- 202 Grade Event Term PtDose N o / Re so lv ed w ith S ta nd ar d of C ar e CRS <24 hours0 2 1 Pyrexia Chills 01-04 D os e Le ve l 1 (1 x 1 09 C A R + N K c el ls / d os e) 5 days < 24 hours 0 3 1 1 Pyrexia Hypotension 08-05 < 24 hours 1 1 2 Pyrexia Hypoxia 12-07 D os e Le ve l 2 /R P2 D (1 .5 x 1 09 C A R + N K c el ls / d os e) 2 7 7 1 2 2 Pyrexia Pyrexia Hypotension 05-18 12Pyrexia 05-20 IRR< 24 hours0 1Pyrexia12-15 1IRR12-22 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 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 21


 
50% of Patients Achieved a Response with SENTI-202 Treatment Dose Level 2/RP2DDose Level 1 All Patients N=18^ 1.5 x 109 CAR+ NK cells/ dose N=12 1 x 109 CAR+ NK cells/ dose N=6 Response 9 (50)6 (50)3 (50)Overall Response Rate (ORR), n (%) 7 (39)5 (42)2 (33)CR/CRh rate, n (%) Response Category, n(%) 5 (28)3 (25)2 (33)CR 2 (11)2 (17)0CRh 2 (11)1 (8)1 (17)MLFS Negative MRD* Status, n/n (%) 5/5 (100)3/3 (100)2/2 (100)in CR patients 6/7 (86)4/5 (80)2/2 (100)in CR/CRh patients 7/9 (78)5/6 (83)2/3 (67)in CR/CRh/MLFS patients 1.2 (1.0, 1.3)1.2 (1.0,1.3)1.2 (1.1,1.2)Median Time to Response (min, max), mo 4.8 (0.9, 17.5)3.1 (0.9, 9.1)8.0 (3.6, 17.5)Median Duration of Follow-Up (min, max) mo ^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) 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 22


 
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 23 CRh


 
Selective AML Blast and Leukemic Stem Cell (LSC) Killing Consistent with SENTI-202 CD33/ FLT3 “OR” Logic Gate Mechanism of Action 24 AML blast reduction on study* 0 20 40 60 80 100 To ta l B on e M ar ro w B la st s (% ) Baseline Best Response LSC reduction on study in Responders (ORR)# * Patient 12-07 had low sample viability 0 0.01 0.1 1 10 100 % C D 34 + C D 38 lo w LS C of a ll ce lls Baseline C1D28 C2D28 * • LSCs in treated patients were mostly quiescent at baseline, and not likely to be responsive to lymphodepleting chemotherapy. • AML blast reduction was noted in all responders (ORR) and in some non-responders. • LSC proportions in responder (ORR) bone marrow decreased at least 10-fold after SENTI-202 treatment. Baseline LSC cell cycle status in all patients# G0 G1 S Cell cycle phase 0 20 40 60 80 100 % o f L SC s Data from an open clinical database of an ongoing study as of 17-Oct-2025; HSC: * Blast reduction as measured by local pathology and assessed by investigators.; # LSC reduction and cell cycle as measured by CyTOF. LSCs were identified as CD34+ CD38-/low cells residing in the AML subpopulation. In patients with CD34- disease (n=2), LSCs were defined as CD38-/low (rather than CD34+ CD38-/low). LSC cell cycle was assessed using Ki-67 and IdU cell cycle markers during CyTOF analysis.


 
Selective Protection of Healthy Hematopoietic Stem & Progenitor Cells (HSPC) Consistent with SENTI-202 “NOT” Logic Gate Mechanism of Action 25 HSPC in Responders (ORR) at baseline 100 1 0.1 0 % H SP C o f a ll ce lls CR/CRh MLFS 10 • Among all responders (ORR), patients with any detectable HSPC at baseline achieved CR/CRh, while patients with no detectable HSPC at baseline achieved MLFS. • In responders achieving CR/CRh, the proportion of HSPCs in bone marrow was increased or maintained. HSPC (CD34+ CD38low) in Responders (ORR) * Patient 12-07 had low sample viability. 100 Baseline C1D28 % H SP C o f a ll ce lls 10 1 0.1 0.01 0 C2D28 * EMCN inhibitory CAR (iCAR) protects healthy cells NOT Logic Gate protects healthy HSC/HSPC from off-tumor, on-target effects • Protects HSC/HSPC even when they express CD33 and/or FLT3 • EMCN is found predominantly on healthy HSC/HSPC, and rarely on AML EMCN iCAR SENTI-202 Data from an open clinical database of an ongoing study as of 17-Oct-2025; HSC: Hematopoietic stem cells. HSPCs were measured by CyTOF. HSPCs were identified as CD34+ CD38-/low cells residing in the healthy cell subpopulations.


 
Rapid Peripheral Blood Cell Count Recovery Consistent with SENTI-202’s Unique NOT Gate Mechanism of Action Data from an open clinical database of an ongoing study as of 17-Oct-2025; Cycles 1 & 2 represented in plot for patients receiving 2 cycles of SENTI-202; CR: complete remission; CRh: CR with partial hematologic recovery; ANC: absolute neutrophil count; PLT: platelet count 26 Threshold for CRh Threshold for CR LD 3 or 5 doses of SENTI-202 per Schedule


 
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 stability 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 27


 
SENTI-202 Demonstrated Promising Results in the Treatment of Relapsed/Refractory Acute Myeloid Leukemia • SENTI-202-101 trial has enrolled heavily treated 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 AEI Grade 1/2 pyrexia that resolves rapidly with standard of care • 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 has received both RMAT and Orphan Drug Designation and expansion cohort continues to enroll • Protocol designed to permit seamless Phase 1 to pivotal study transition 28


 
29 Next Steps to Accelerate SENTI-202 into Pivotal Study *Assumes additional financing to continue pivotal process development end of 2025 and to support enrolment of dose expansion patients in 2026 20262025Product SENTI-202 Clinical Trial* SENTI-202 CMC Process 20 patients dosed, RP2D confirmed RMAT and ODD designation granted Durable (7.6 mo), ~40% CR/CRh and 50% CR rate, 100% MRD- CR Excellent safety profile Pivotal R/R AML Study, Additional Indications Phase 1 SENTI-202 Manufacturing Pivotal SENTI-202 Process Development Pivotal SENTI-202 Manufacturing FDA Interaction on Pivotal Study Plans


 
Tim Lu, MD, PhD CEO and Co-Founder 30


 
First-in-Class Off-the-Shelf Logic-Gated Selective CD33 OR FLT3 NOT EMCN CAR NK Cell Therapy Investment from Leading Healthcare Institutional Investors Lead Program SENTI-202 SENTI-202 Summary 31 *CR: Complete Remission; CRh: CR with partial hematologic recovery; cCR: composite Complete Remission; MRD: Measurable Residual Disease; AML: Acute Myeloid Leukemia  Clinical Proof of Concept further validated with 20 Relapsed Refractory (R/R) AML patients treated in ongoing multinational, multicenter Phase 1 trial  Recommended Phase 2 Dose confirmed  Durable responses with 50% ORR and 42% CR/CRh rates at RP2D, 7.6mo estimated median duration of cCR overall  High MRD-negative rates (e.g., 100% CRs MRD-)  Excellent safety profile, outpatient dosing potential  Confirmed Mechanism of Action of selective killing of AML blasts and leukemic stem cells, with sparing of healthy bone marrow stem cells  FDA Regenerative Medicine Advanced Therapy (RMAT) Designation and Orphan Drug Designation (ODD)  Next steps: Launch pivotal trial & expand into other indications (e.g., Newly Diagnosed AML) in 2026  Validated Logic Gate technology can be expanded into other modalities (e.g., T, in vivo CAR) for additional cancers


 
Programming Gene Circuits to Enhance the Potential of Cell and Gene Therapies SENTI BIO CONFIDENTIAL, #CT014 32 Multi-Arming to address Immunosuppressive Tumor Microenvironments Regulator Dial to enable Control for Safety Smart Sensor to enable Specificity for Disease Logic Gating to address Antigen Escape and Specificity Sense diseased vs healthy cells (e.g., SENTI-202) Stimulate immune cells, overcome TME, promote NK cell function Dial payload expression up/down Cell/disease-specific promoters Therapeutic transgene expressed Gene Circuits


 
Senti’s Gene Circuits can be Used Across Diverse Cell and Gene Therapy Modalities iPSCs In vivo cell therapy AAVs & other gene therapy modalities T cells NK cells Gene Circuit Multi-Arming Regulator Dial Smart Sensor Logic Gating Technology 33


 
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