Slide 1: SENTI-202: Positive Preliminary Results in Relapsed/Refractory Hematologic Malignancies Including AML
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
Slide 2: Forward Looking Statements
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 an
Slide 3: Company Highlights
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 har
Slide 4: Logic Gates in Cell Therapy
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 A
Slide 5: AML Is an Aggressive Leukemia with Poor Prognosis
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:
Slide 6: SENTI-202: Intelligently Designed CAR-NK May Overcome Limitations of Current Therapies Against AML
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 prot
Slide 7: SENTI-202 Scalable Manufacturing Process
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 tra
Slide 8: SENTI-202 Phase 1 Trial (SENTI-202-101) Design
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
Slide 9: SENTI-202-101 Dosing Schema - Preliminary RP2D Identified
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
Slide 10: Study Enrolled a High-Risk R/R AML Population
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
Slide 11: Study Subjects had Received Multiple Prior Therapies
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 pr
Slide 12: Patients Received a Median of 2 Cycles of SENTI-202 Therapy
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 wi
Slide 13: Preliminary Safety Data Indicate SENTI-202 is Well Tolerated
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 ong
Slide 14: SENTI-202 Related AEIs Were Low Grade and Manageable
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,
Slide 15: Responses Observed Across All Dose Cohorts
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 (
Slide 16: Rapid Bone-Marrow Blast Reduction Observed Across All Dose Cohorts
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
Slide 17: Early Deep Responses Noted Across Dose Levels with Durability 8+ Months
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 ag
Slide 18: CyTOF Bone Marrow Data Shows Decreased LSCs in Responders
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 bas
Slide 19: Rapid Normalization of Peripheral Blood Cell Count with HSPC Protection
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 o
Slide 20: SENTI-202 Detected in Periphery of All Treated Patients
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 wi
Slide 21: Dosing and Safety Conclusions
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/N
Slide 22: Efficacy Conclusions
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 w
Slide 23: Also at AACR…
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/
Slide 24: Acknowledgements
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
Slide 25: Q&A
Q&A 25