Senti Biosciences Holdings, Inc. · NASDAQ:SNTI
Senti Biosciences — Investor Day (December 2022)
34 slides from Senti Biosciences's investor day presentation, Dec 12, 2022
Slide 1: Investor Event December 2022
™ D E C E M B E R 2 0 2 2 IN V E ST O R E V E N T | SE N T I B IO SC IE N C E S Investor Event 1 December 2022
Slide 2: Disclaimer: Forward Looking Statements
D E C E M B E R 2 0 2 2 IN V E ST O R E V E N T | SE N T I B IO SC IE N C E S Disclaimer 2 Forward Looking Statements This presentation contains forward-looking statements. Statements we make in this presentation may include statements which are not historical facts and are considered forward-lookin
Slide 3: Agenda
D E C E M B E R 2 0 2 2 IN V E ST O R E V E N T | SE N T I B IO SC IE N C E S Agenda 3 Gene Circuits to Engineer Next Generation Cell Therapies Tim Lu, MD, PhD – Co-founder & CEO Treatment Paradigm and Unmet Medical Need in AML Stephen A. Strickland, Jr., MD, MSCI - Director of Leukemia Research at
Slide 4: Gene Circuits to Engineer Next Generation Cell Therapies
D E C E M B E R 2 0 2 2 IN V E ST O R E V E N T | SE N T I B IO SC IE N C E S Gene Circuits to Engineer Next Generation Cell Therapies Tim Lu, MD, PhD - Co-founder & CEO 4
Slide 5: Senti's Next Generation Gene Circuit Technologies for Cancer Cell Therapy
D E C E M B E R 2 0 2 2 IN V E ST O R E V E N T | SE N T I B IO SC IE N C E S Senti’s Next Generation Gene Circuit Technologies for Cancer Cell Therapy 5 Broaden patient access Address efficacy AND safety Address large unmet needs across multiple solid and liquid tumors Enhance durability and persis
Slide 6: Today's Cell Therapies Are Largely Guided by Single CAR System
D E C E M B E R 2 0 2 2 IN V E ST O R E V E N T | SE N T I B IO SC IE N C E S Today’s Cell Therapies Are Largely Guided by Single CAR System and Limited to a Small Set of Potential Therapeutic Targets 6 Only ~5% of potential surface proteins have been utilized in CAR therapies Heterogeneous antigen
Slide 7: Gene Circuit Technology Can Expand the Range of CAR Cell Therapies
D E C E M B E R 2 0 2 2 IN V E ST O R E V E N T | SE N T I B IO SC IE N C E S Senti’s Gene Circuit Technology Has the Potential to Expand the Range of CAR Cell Therapies With Enhanced Efficacy and Precision 7 Expanding the range of potential therapeutics into the “empty” space Inhibitory CAR: NOT GA
Slide 8: Gene Circuits Designed to Solve for Key Cell Therapy Challenges
D E C E M B E R 2 0 2 2 IN V E ST O R E V E N T | SE N T I B IO SC IE N C E S Gene Circuits Designed to Solve for Key Cell Therapy Challenges 8 Senti’s Gene Circuit Solutions Cancer Cell Therapy Challenges Lack of NK cell expansion and persistence Antigen escape and tumor heterogeneity Dirty targets
Slide 9: NK Cells Compare Favorably to T Cell Based Therapies
D E C E M B E R 2 0 2 2 IN V E ST O R E V E N T | SE N T I B IO SC IE N C E S NK Cells Compare Favorably to T Cell Based Therapies, While Gene Circuits Have Potential to Further Improve Efficacy, Safety, and Durability Further 9 NK cells are an attractive modality vs T cells • Extensive clinical exp
Slide 10: Senti's Next Generation CAR-NK Cell Therapy Pipeline
D E C E M B E R 2 0 2 2 IN V E ST O R E V E N T | SE N T I B IO SC IE N C E S Senti’s Next Generation CAR-NK Cell Therapy Pipeline Tackles Hard to Treat Cancers With Gene Circuits 10 Program Target Indications Discovery IND enabling Phase 1 Gene Circuits SENTI-202 CD33 and/or FLT3 AML, MDS and other
Slide 11: SENTI-202, a Novel, Multi-Armed, Off-The-Shelf, Selective CAR-NK Cell Therapy
D E C E M B E R 2 0 2 2 IN V E ST O R E V E N T | SE N T I B IO SC IE N C E S SENTI-202, a Novel, Multi-Armed, Off-The-Shelf, Selective CAR-NK Cell Therapy for Blood Cancers Including AML and MDS 11LSCs: Leukemic Stem Cells Multi-Armed, off-the-shelf, selective CAR-NK • OR GATE: bivalent CD33 and/or
Slide 12: SENTI-202 Logic Gates Designed to Clear AML Blasts and LSCs
D E C E M B E R 2 0 2 2 IN V E ST O R E V E N T | SE N T I B IO SC IE N C E S EMCN Engagement Enables Protection of Healthy HSCs FLT3 OR CD33 Engagement Triggers Killing of Heterogeneous AML Cancer Cells SENTI-202 Logic Gates Are Designed to Achieve Deep Clearance of AML Blasts and LSCs While Sparin
Slide 13: Proprietary crIL-15 Technology Enhances NK Cell Expansion and Persistence
D E C E M B E R 2 0 2 2 IN V E ST O R E V E N T | SE N T I B IO SC IE N C E S crIL-15 Senti’s Proprietary crIL-15 Technology Aims to Enhances NK Cell Expansion, Persistence and Tumor Killing 13 1. CYTOKINE SECRETION ONLY (PARACRINE) Enhanced NK Cell Expansion, Persistence and Tumor Killing 3. CALIBR
Slide 14: Scalable Manufacturing to Support Off-The-Shelf CAR-NK Products
D E C E M B E R 2 0 2 2 IN V E ST O R E V E N T | SE N T I B IO SC IE N C E S Scalable Manufacturing to Support Off-The-Shelf CAR-NK Products 14 Lentivi rus Outpatient use potential Patient Isolate from selected donors Thaw and infuse Scalable ~21 Day Process NK Cells Selected Donor Gene Circuit Eng
Slide 15: Treatment Paradigm and Unmet Medical Need in AML
D E C E M B E R 2 0 2 2 IN V E ST O R E V E N T | SE N T I B IO SC IE N C E STreatment Paradigm and Unmet Medical Need in AML Stephen A. Strickland, Jr., MD, MSCI - Director of Leukemia Research at the Sarah Cannon Transplant & Cellular Therapy Network 15
Slide 16: History of FDA Approvals and Current Clinical Trials in AML
DO NOT DISTRIBUTE 1973 Cytarabine/ Daunorubicin (7+3) 2000 Gemtuzumab ozogamicin 1977 First bone marrow transplant 2002 Idarubicin 2017 Midostaurin, Gemtuzumab ozogamicin (re- approved), CPX- 351, Enasidenib 2010 Gemtuzumab ozogamicin (withdrawal) 2018 Ivosidenib, Gilteritinib, Venetoclax, Glasdegib
Slide 17: Significant Unmet Need in AML Even with Recent Approvals
DO NOT DISTRIBUTE Significant Unmet Need in AML Even with Recent Approvals 1 Clarivate source data 2022; 2 Mangan Ther Adv Hematology 2011; 3 Brandwein Figure from Brandwein Am J Blood 2020 5.3 months median OS 12.6% 5-year OS AML • ~14,000 patients are newly diagnosed with AML in the US1 • Treatmen
Slide 18: AML Is a Heterogenous Disease and Requires Multi-Antigen Targeting
DO NOT DISTRIBUTE AML Is a Heterogenous Disease and Requires Multi-Antigen Targeting SC-DARIC-33 JEZ-567 PRGN-3006 Targets Expressed on AML Blasts And/Or LSCs ICG-144 Target Antigen Expression on Various Cells1 Antigen LSCs Blasts HSCs CD33 (SIGLEC3) +/- + +/- FLT3 (CD135) + +/- + CLL-1 (CLEC12A) +/
Slide 19: The Need to Limit On-Target / Off-Tumor Toxicity in AML
DO NOT DISTRIBUTE The Need to Limit On-Target / Off-Tumor Toxicity in AML ESAs = Erythropoiesis-stimulating agents, G-CSF = Granulocyte colony stimulating factor Myelosuppression Anemia Thrombocytopenia Neutropenia Consequence Fatigue Risk of bleeding Risk of infection Targeting HSPCs leads to… • Co
Slide 20: Update on SENTI-202 For Heme Malignancies
D E C E M B E R 2 0 2 2 IN V E ST O R E V E N T | SE N T I B IO SC IE N C E SUpdate on SENTI-202 For Heme Malignancies Kanya Rajangam, MD, PhD - CMDO 20
Slide 21: SENTI-202 for CD33 and/or FLT3 Expressing Blood Cancers Including AML
D E C E M B E R 2 0 2 2 IN V E ST O R E V E N T | SE N T I B IO SC IE N C E S SENTI-202 for CD33 and/or FLT3 Expressing Blood Cancers Including AML 21 7,860 7 20,216 Protein Coding Genes 40 2,611 Membrane proteins High expression in AML Low non-hematopoietic expression Manual curation FLT3 and CD33
Slide 22: SENTI-202 Has Shown Robust Preclinical Anti-Tumor Activity
D E C E M B E R 2 0 2 2 IN V E ST O R E V E N T | SE N T I B IO SC IE N C E S SENTI-202 Has Shown Robust Preclinical Anti-Tumor Activity 22 Vehicle Unengineered NK Cells SENTI-202 CAR- NK Cells Day: 7 28 34 Significant in vitro killing of leukemia cell line Robust suppression of tumor in AML MV4-11
Slide 23: Discovery Platform Identified EMCN as Key Protective Antigen for Healthy HSCs
D E C E M B E R 2 0 2 2 IN V E ST O R E V E N T | SE N T I B IO SC IE N C E S Senti’s Discovery Platform Identified EMCN as a Key Protective Antigen for Healthy HSCs 23 Surface Protein 0% EMCN on primary AML LSCs EMCN Si d e Sc at te r (S SC ) 70% EMCN on primary HSCs Challenge Solution and Validati
Slide 24: Discovery Platform Identified LIR1 as the Optimal iCAR ICD
D E C E M B E R 2 0 2 2 IN V E ST O R E V E N T | SE N T I B IO SC IE N C E S Senti’s Discovery Platform Identified LIR1 as the Optimal iCAR ICD for SENTI-202 24 Systematic approach to identify optimal iCAR ICD for SENTI-202 using a screen of native inhibitory proteins Anti-FLT3 scFV CD28 CD3ZH TM N
Slide 25: SENTI-202 Preclinical Selectivity via Inhibitory CAR Binding Endomucin
D E C E M B E R 2 0 2 2 IN V E ST O R E V E N T | SE N T I B IO SC IE N C E S SENTI-202 Preclinical Selectivity via Inhibitory CAR Binding Endomucin to Protect Healthy Primary Human HSCs 25 In vitro protection of healthy primary human HSC fraction expressing EMCN 0 10 20 30 40 50 60 CD33 and/or FLT3
Slide 26: EMCN iCAR Protects Model Healthy Cells In Vivo
D E C E M B E R 2 0 2 2 IN V E ST O R E V E N T | SE N T I B IO SC IE N C E S SENTI-202 Preclinical Selectivity via EMCN iCAR Protects Model Healthy Cells In Vivo from aCAR-Mediated Killing 26 I.V. injection Blood draw After 27 days N o rm al iz e d C o u n ts N o rm al iz e d C o u n ts N o rm al i
Slide 27: crIL-15 Increases Persistence and Activation of CAR-NK and Immune Cells
D E C E M B E R 2 0 2 2 IN V E ST O R E V E N T | SE N T I B IO SC IE N C E S Calibrated Release IL-15 (crIL-15) Increases Persistence and Activation of Both CAR-NK and Immune Cells in Tumor Milieu 27 0 2,000 4,000 6,000 sIL-15 CAR-NK crIL-15 CAR-NK Pa ra cr in e A ct iv it y (p ST AT 5 M FI ) Phosp
Slide 28: Proposed Phase 1 Study in R/R CD33+ and/or FLT3+ Malignancies
D E C E M B E R 2 0 2 2 IN V E ST O R E V E N T | SE N T I B IO SC IE N C E S Proposed Phase 1 Study in R/R CD33+ And/or FLT3+ Malignancies With Focus on AML 28 Proposed Phase 1 study anticipated to enroll R/R CD33+ and/or FLT3+ heme malignancies • Modified “3+3” study design • Enroll patients who h
Slide 29: Conclusions and Next Steps
D E C E M B E R 2 0 2 2 IN V E ST O R E V E N T | SE N T I B IO SC IE N C E SConclusions and Next Steps Tim Lu, MD, PhD - Co-founder & CEO 29
Slide 30: SENTI-202 Can Potentially Fulfill AML Treatment Gap
D E C E M B E R 2 0 2 2 IN V E ST O R E V E N T | SE N T I B IO SC IE N C E S SENTI-202 Can Potentially Fulfill AML Treatment Gap 30 Multi-Arming Multi-Antigen Targeting Healthy Cell Protection Redosing Potential Scalable Manufacturing SENTI-202 Calibrated release IL-15 enhances NK cell expansion, p
Slide 31: SENTI-202 Aims to Fill Key Unmet Need of Targeting Both AML Blasts and LSCs
D E C E M B E R 2 0 2 2 IN V E ST O R E V E N T | SE N T I B IO SC IE N C E S SENTI-202 Aims to Fill Key Unmet Need of Targeting Both AML Blasts and AML LSCs 311 HSC toxicity was observed for several preclinical FLT3-targeted therapies, including CAR-T, ADCs and BiTes Select AML Cell Therapy Candida
Slide 32: YTD Progress and Planned Milestones in the Next 12 Months
D E C E M B E R 2 0 2 2 IN V E ST O R E V E N T | SE N T I B IO SC IE N C E S YTD Progress and Planned Milestones in the Next 12 Months 32 SENTI-202 IND in 2H 2023 Pre-clinical data updates from multiple CAR-NK programs planned at key scientific meetings in 2023 GMP facility buildout on track to ena
Slide 33: Gene Circuits Can Vastly Expand the Universe of Cancer Targets
D E C E M B E R 2 0 2 2 IN V E ST O R E V E N T | SE N T I B IO SC IE N C E S Gene Circuits Can Vastly Expand the Universe of Cancer Targets and Tumors That Can Be Addressed With Cell Therapies 33 Heme Malignancies Solid Tumors N ee d f o r H ea lt h y C el l P ro te ct io n FLT3* CD33* CEA* Target
Slide 34: Q&A
D E C E M B E R 2 0 2 2 IN V E ST O R E V E N T | SE N T I B IO SC IE N C E S Q&A 34