Senti Biosciences Holdings, Inc. · NASDAQ:SNTI
Senti Biosciences — Investor Presentation (January 2023)
35 slides from Senti Biosciences's investor presentation, Jan 9, 2023
Slide 1: Corporate Presentation
™ JA N U A R Y 2 0 2 3 | SE N T I B IO SC IE N C E S Corporate Presentation 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 Pioneering Smarter Next Generation Cell and Gene Therapies 3 Pipeline of CAR-NK Cell Therapies Diseases: blood cancers and solid tumors Gene Circuit advantages: multi-arming, selectivity and control Manufacturing: off-the-shelf, scalable with outpat
Slide 4: 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 4 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 5: 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 5
Slide 6: 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 6 Senti’s Gene Circuit Solutions Cancer Cell Therapy Challenges Lack of NK cell expansion and persistence Antigen escape and tumor heterogeneity Dirty targets (on-target, off-tumor toxi
Slide 7: 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 7 Extensive clinical experience with allogeneic donor-derived unengineered NK cells1 • ~70 global peripheral blood derived unengineered NK cell therapy clinical trials1 • Well-tolerated (~500 pati
Slide 8: 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 8 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 9: Senti's Discovery Platform for Tumor-Associated and Protective Antigens
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 9 52 31 Expression in tumor cells A B C 4 Healthy tissue expression of A Expression in tumor cells D E F 1
Slide 10: 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 10 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 11: 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 11 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 12: Manufacturing
JA N U A R Y 2 0 2 3 | SE N T I B IO SC IE N C E S Manufacturing 12
Slide 13: 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 13 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 14: 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 14 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 15: 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 15 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 16: 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 16
Slide 17: 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 17 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 18: 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 18 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 19: 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 19 In vitro protection of healthy primary human HSC fraction expressing EMCN Endomucin was identified and validated by bioinformatics, flow
Slide 20: 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 20 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 21: 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 21 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 22: 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 22 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 23: SENTI-301A Preclinical Activity and Proposed Phase 1 Study
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 and Proposed Phase 1 Study in Advanced Solid Tumors With Focus on HCC 23 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 Days Vehicle Unengineered NK Cells SENTI-301A CAR-NK Cells Proposed Phase 1 st
Slide 24: 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 24 Multi-Armed, off-the-shelf, selective CAR-NK • CEACAM5 (CEA) activating CAR → metastic colorectal cancer (mCRC) and other solid tumors • NOT GATE: inhibition by VSIG2 antigen on healthy epithelial cells →
Slide 25: 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 26: Robust Preclinical Activity With CEA CAR-NK Cells Augmented by Multi-Arming
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 That Is Augmented by Multi- Arming With Both crIL-15 and IL-21 26 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 N
Slide 27: Paired Target and Protective Antigen Approach 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+ Senti’s Approach to Select Paired Target and Protective Antigens Translates to Rapid Preclinical Proof of Principle for Protecting
Slide 28: 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 28 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 29: 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 29
Slide 30: 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 30 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 31: 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 31 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 32: 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 33: 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 33 Wholly-Owned Programs with Opportunities for Future Development Opportunities for Future Development and Additional Partnering Multi-Arming Logic Gating R
Slide 34: 2022 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 2022 Milestones and Upcoming Value Driving Milestones 34 Program 2022 Completed Milestones 2023 Anticipated Milestones SENTI-202 CD33 and/or FLT3 AML, MDS and other blood cancers SENTI-301A GPC3 HCC and other solid tumors SENTI-401 CEA CRC and other
Slide 35: 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 35
Senti Biosciences — Investor Presentation (January 2023) on 6ix