Senti Biosciences Holdings, Inc. · NASDAQ:SNTI
Senti Biosciences — Investor Presentation (January 2023)
39 slides from Senti Biosciences's investor presentation, Jan 27, 2023
Slide 1: Engineering the Future of Cell and Gene Therapies
™ JA N U A R Y 2 0 2 3 | SE N T I B IO SC IE N C E S Engineering the Future of Cell and Gene Therapies 1 January 2023
Slide 2: Disclaimer
JA N U A R Y 2 0 2 3 | 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-looking within the meaning of Sec
Slide 3: Pioneering Smarter Next Generation Cell and Gene Therapies
JA N U A R Y 2 0 2 3 | SE N T I B IO SC IE N C E S Gene Circuits Multi-Arming Logic Gating (OR and NOT GATEs) Regulator Dial Smart Sensor to reprogram cells to sense, compute, and respond to disease Pioneering Smarter Next Generation Cell and Gene Therapies 3 Pipeline of CAR-NK Cell Therapies Diseas
Slide 4: Senti's Gene Circuit Technology Has Broad Potential Across Modalities and Therapeutic Areas
JA N U A R Y 2 0 2 3 | SE N T I B IO SC IE N C E S Senti’s Gene Circuit Technology Has Broad Potential Across Modalities and Therapeutic Areas 4 Wholly-Owned Programs with Opportunities for Future Development Opportunities for Future Development and Additional Partnering Multi-Arming Logic Gating Re
Slide 5: Industry-Leading Management With Top-Tier Board and Scientific Advisors
JA N U A R Y 2 0 2 3 | SE N T I B IO SC IE N C E S Industry-Leading Management With Top-Tier Board and Scientific Advisors 5 Executive Team James Collins, PhD Scientific Co-Founder, MIT Wilson Wong, PhD Scientific Co-Founder, Boston University Ahmad (Mo) Khalil, PhD Boston University Martin Fusseneg
Slide 6: CAR-NK Cell Therapy Pipeline
JA N U A R Y 2 0 2 3 | SE N T I B IO SC IE N C E S CAR-NK Cell Therapy Pipeline 6
Slide 7: Gene Circuits Designed to Solve for Key Cell Therapy Challenges
JA N U A R Y 2 0 2 3 | SE N T I B IO SC IE N C E S Gene Circuits Designed to Solve for Key Cell Therapy Challenges 7 Senti’s Gene Circuit Solutions Cancer Cell Therapy Challenges Lack of cell expansion and persistence Antigen escape and tumor heterogeneity Dirty targets (on-target, off-tumor toxicit
Slide 8: NK Cells Compare Favorably to T Cell Based Therapies
JA N U A R Y 2 0 2 3 | SE N T I B IO SC IE N C E S NK Cells Compare Favorably to T Cell Based Therapies 81 Lamers-Kok Journal of Hematology & Oncology 2022; 2 Bachier 2021 Capabilities Current Auto T Cells Off-the-shelf potential with broad patient accessibility Designed with Logic Gates to achieve
Slide 9: Peripheral Blood-Sourced NK Cells Provide Multiple Advantages for Next Generation CAR-NK Cell Therapies
JA N U A R Y 2 0 2 3 | SE N T I B IO SC IE N C E S 9 Peripheral Blood-Sourced NK Cells Provide Multiple Advantages for Next Generation CAR-NK Cell Therapies Features Cord Blood NK Cells NK Cell Expandability Potency and Function Genetic Engineering Increased expansion potential but smaller number of
Slide 10: Calibrated Release IL-15 Increases Persistence and Activation of CAR-NK and Immune Cells
JA N U A R Y 2 0 2 3 | 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 10 0 1 2 3 4 5 0 1 2 3 4 5 6 7 8 9 Tu m o r C el l A b u n d an ce Days Vehicle Unengineered NK Cells crIL-15 CAR-NK Cells sIL-15
Slide 11: Today's Cell Therapies Are Largely Guided by Single CAR System
JA N U A R Y 2 0 2 3 | 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 11 Only ~5% of potential surface proteins have been utilized in CAR therapies On-target / off-tumor killing leading to poor th
Slide 12: Gene Circuit Technology Can Expand the Range of CAR Cell Therapies
JA N U A R Y 2 0 2 3 | 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 12 Expanding the range of potential therapeutics into the “empty” space Inhibitory CAR: NOT GATESenti’s next-gen capabil
Slide 13: Discovery Platform for Tumor-Associated Antigen and Protective Antigen
JA N U A R Y 2 0 2 3 | SE N T I B IO SC IE N C E S Senti’s Discovery Platform for Tumor-Associated Antigen and Protective Antigen to Generate Many Targets for New Logic Gated CAR-NK Candidates 13 52 31 Expression in tumor cells A B C 4 Healthy tissue expression of A Expression in tumor cells D E F 1
Slide 14: Gene Circuits Can Vastly Expand the Universe of Cancer Targets
JA N U A R Y 2 0 2 3 | 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 14 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 GPC3* OR GATE to enhance ef
Slide 15: Senti's Next Generation CAR-NK Cell Therapy Pipeline Tackles Hard to Treat Cancers
JA N U A R Y 2 0 2 3 | 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 15 Program Target Indications Discovery IND enabling Phase 1 Gene Circuits SENTI-202 CD33 and/or FLT3 AML, MDS and other blood cancers ✓ Multi-Arming: designed for en
Slide 16: Manufacturing
JA N U A R Y 2 0 2 3 | SE N T I B IO SC IE N C E S Manufacturing 16
Slide 17: Scalable Manufacturing to Support Off-The-Shelf CAR-NK Products
JA N U A R Y 2 0 2 3 | SE N T I B IO SC IE N C E S Scalable Manufacturing to Support Off-The-Shelf CAR-NK Products 17 Lentivi rus Outpatient use potential Patient Isolate from selected donors Thaw and infuse Scalable ~21 Day Process NK Cells Selected Donor Gene Circuit Engineered CAR-NK cells Engine
Slide 18: Senti Selects NK Cell Donors to Support Robust Cell Expansion
JA N U A R Y 2 0 2 3 | SE N T I B IO SC IE N C E S Senti Selects NK Cell Donors to Support Robust Cell Expansion 18 Senti screens and selects GMP donors using NK cell expansion and other functional attributes to minimize variability 1.E+08 1.E+09 1.E+10 1.E+11 1.E+12 1.E+13 1.E+14 1.E+15 0 10 20 30
Slide 19: Cryopreservation Process Retains High Potency of CAR-NK Products
JA N U A R Y 2 0 2 3 | SE N T I B IO SC IE N C E S Senti’s Cryopreservation Process Retains High Potency of CAR-NK Products Supporting Multi-Country and Multi-Site Clinical Evaluation 19 0 10 20 30 40 50 60 70 80 90 100 Pre-Freeze Post-Thaw % V ia b le C el ls CAR-NK cell viability retained post-tha
Slide 20: Pipeline Products
JA N U A R Y 2 0 2 3 | SE N T I B IO SC IE N C E S Pipeline Products 20
Slide 21: SENTI-202 for CD33 and/or FLT3 Expressing Blood Cancers
JA N U A R Y 2 0 2 3 | SE N T I B IO SC IE N C E S SENTI-202 for CD33 and/or FLT3 Expressing Blood Cancers 21 Multi-Armed, off-the-shelf, selective CAR-NK • OR GATE: bivalent CD33 and/or FLT3 activation → potential for deep and durable responses in acute myeloid leukemia (AML) and other blood cancer
Slide 22: SENTI-202 Aims to Address Unmet Needs in FLT3 and/or CD33 Expressing Blood Cancers
JA N U A R Y 2 0 2 3 | SE N T I B IO SC IE N C E S SENTI-202 Aims to Address Unmet Needs in FLT3 and/or CD33 Expressing Blood Cancers With a Focus on AML 22 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
Slide 23: SENTI-202 Has Shown Robust Preclinical Activity Across Multiple AML/MDS Models
JA N U A R Y 2 0 2 3 | SE N T I B IO SC IE N C E S SENTI-202 Has Shown Robust Preclinical Activity Across Multiple AML / MDS Models 23 Broad in vitro killing of primary AML and MDS tumor cells In vivo suppression of tumor and increased mouse survival in MV4-11 AML NSG mouse model AML #1 0 10 20 30 4
Slide 24: SENTI-202 Preclinical Selectivity via Inhibitory CAR Binding Endomucin
JA N U A R Y 2 0 2 3 | 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 24 In vitro protection of healthy primary human HSC fraction expressing EMCN Endomucin was identified and validated by bioinformatics, flow
Slide 25: Proposed Phase 1 Study in R/R CD33+ and/or FLT3+ Malignancies
JA N U A R Y 2 0 2 3 | 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 25 Proposed Phase 1 study anticipated to enroll R/R CD33+ and/or FLT3+ heme malignancies • Modified “3+3” study design • Received at least 1 prior treatment including ta
Slide 26: SENTI-401 for CEA Expressing Solid Tumors
JA N U A R Y 2 0 2 3 | SE N T I B IO SC IE N C E S SENTI-401 for CEA Expressing Solid Tumors 26 Multi-Armed, off-the-shelf, selective CAR-NK • CEACAM5 (CEA) activating CAR → metastatic colorectal cancer (mCRC) and other solid tumors • NOT GATE: inhibition by VSIG2 antigen on healthy epithelial cells
Slide 27: SENTI-401 Aims to Address Unmet Needs in CEA Expressing Solid Tumors
JA N U A R Y 2 0 2 3 | SE N T I B IO SC IE N C E S Colorectal Cancer Gastric Cancer Lung Cancer Pancreatic Cancer Breast Cancer Colon/Rectum Pancreas Lung Stomach Esophagus Healthy Tissues With CEA Overexpression3 Tumor Types With CEA Overexpression3 SENTI-401 Aims to Address Unmet Needs in CEA Expr
Slide 28: Robust Preclinical Activity With CEA CAR-NK Cells Multi-Armed With crIL-15 and IL-21
JA N U A R Y 2 0 2 3 | SE N T I B IO SC IE N C E S Robust Preclinical Activity With CEA CAR-NK Cells Multi-Armed With Both crIL-15 and IL-21 28 Arming CEA CARs with the combination of Senti’s proprietary crIL-15 and IL-21 results in improved anti-tumor activity of NK cells 1 Nature 2018 0 1 2 3 4 5
Slide 29: Approach to Select Paired Target and Protective Antigens Protects Healthy VSIG2+ Cells
JA N U A R Y 2 0 2 3 | SE N T I B IO SC IE N C E S 0 20 40 60 80 100 CEA CAR-NK Cells CEA NOT VSIG2 CAR-NK Cells Ta rg et C el l K ill in g (% ) VSIG2- CEA+ VSIG2+ CEA+ Colorectal cancer CEACAM5 VSIG2 CEACAM5: 85-90% of CRC and 40-60% of other solid tumors including lung cancer1 VSIG2 was identified
Slide 30: SENTI-301A for GPC3 Expressing Solid Tumors
JA N U A R Y 2 0 2 3 | SE N T I B IO SC IE N C E S SENTI-301A for GPC3 Expressing Solid Tumors 30 Multi-Armed, off-the-shelf, selective CAR-NK • GPC3 activating CAR → hepatocellular carcinoma (HCC) and other solid tumors • crIL-15 → potential for increased persistence, autocrine and paracrine immune
Slide 31: SENTI-301A Aims to Address Unmet Needs in GPC3 Expressing Solid Tumors
JA N U A R Y 2 0 2 3 | SE N T I B IO SC IE N C E S SENTI-301A Aims to Address Unmet Needs in GPC3 Expressing Solid Tumors With a Focus on HCC 31 GPC3 is an attractive cancer target • Glypican-3 (GPC3) is a membrane-bound protein normally expressed in fetal tissues such as liver and placenta. • After
Slide 32: SENTI-301A Preclinical Anti-Cancer Activity
JA N U A R Y 2 0 2 3 | SE N T I B IO SC IE N C E S SENTI-301A Preclinical Anti-Cancer Activity 32 Group Vehicle Unengineered NK Cells SENTI-301A CAR-NK Cells Median Survival (Days) 48 49.5 93.5 Effective in vitro serial killing of HepG2 cell line 0 1 2 3 0 1 2 3 4 5 6 Tu m o r C el l A b u n d an ce
Slide 33: Regulator Dial Enables On-Demand Production of crIL-12
JA N U A R Y 2 0 2 3 | SE N T I B IO SC IE N C E S Senti’s Regulator Dial Enables On-Demand Production of crIL-12 Controlled via Multiple Distinct FDA-Approved Small Molecule Oral Drugs 33 Dose-dependent, reversible crIL-12 controlled by GRZ in vivo Vehicle GRZ at 50 mg/kg GRZ at 100 mg/kg 1 10 100
Slide 34: Platform and Collaboration Opportunities
JA N U A R Y 2 0 2 3 | SE N T I B IO SC IE N C E S Platform and Collaboration Opportunities 34
Slide 35: Multiple Platform Collaborations Extend Utility of Gene Circuits
JA N U A R Y 2 0 2 3 | SE N T I B IO SC IE N C E S Multiple Platform Collaborations Extend Utility of Gene Circuits 35 Program Indications Gene Circuit Discovery IND enabling Phase 1 Rights Gene Therapies for Tissue-Directed Targets GC-1001/GC-1002 Eye Smart Sensor GC-1003/GC-1004 CNS Smart Sensor G
Slide 36: Two Collaborations to Develop Next Generation Cell and Gene Therapies
JA N U A R Y 2 0 2 3 | SE N T I B IO SC IE N C E S Two Collaborations to Develop Next Generation Cell and Gene Therapies 36 AAV Gene Therapy with Cell Type-Specific Smart Sensor AAV Capsid Therapeutic Payload Low payload expression in OFF Target cell type(s) Compact promoter size to accommodate ther
Slide 37: Smart Sensor Promoters Are Designed to Address Key Challenges in Gene Therapy
JA N U A R Y 2 0 2 3 | SE N T I B IO SC IE N C E S Constitutive control promoter >100% strength of CAG ~10,000-fold specificity Iterative performance optimization Sp e ci fi ci ty (r at io O N :O FF t ar ge t ce ll lin es ) Strength (fraction of CAG, an industry standard constitutive promoter) Smart
Slide 38: Completed Milestones and Upcoming Value Driving Milestones
JA N U A R Y 2 0 2 3 | SE N T I B IO SC IE N C E S Program 2022 Completed Milestones 2023 Anticipated Milestones SENTI-202 CD33 and/or FLT3 AML, MDS and other blood cancers Presented key preclinical data at ASH in December 2022 File IND application in 2H 2023 SENTI-401 CEA CRC and other solid tumors
Slide 39: Thank you
JA N U A R Y 2 0 2 3 | SE N T I B IO SC IE N C E S Thank you 39
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