Senti Biosciences Holdings, Inc. · NASDAQ:SNTI
Senti Biosciences — Investor Presentation (November 2022)
34 slides from Senti Biosciences's investor presentation, Nov 10, 2022
Slide 1: Corporate Presentation November 2022
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S Corporate Presentation November 2022 ™
Slide 2: Disclaimer: Forward Looking Statements
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 2 Disclaimer 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
Slide 3: Pioneering Smarter Next Generation Cell and Gene Therapies
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 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 outpatient potential Platform Collaborations Precise gene therap
Slide 4: Industry-Leading Management With Top-Tier Board and Scientific Advisors
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 4 Industry-Leading Management With Top-Tier Board and Scientific Advisors Executive Team James Collins, PhD Scientific Co-Founder, MIT Wilson Wong, PhD Scientific Co-Founder, Boston University Ahmad (Mo) Khalil, PhD Boston University Martin Fusse
Slide 5: CAR-NK Cell Therapy Pipeline
N O V E M B E R 2 0 2 2 | 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
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 6 Gene Circuits Designed to Solve for Key Cell Therapy Challenges 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 t
Slide 7: NK Cells Compare Favorably to T Cell Based Therapies
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S Extensive clinical experience with allogeneic donor-derived unengineered NK cells1 • Nearly 600 patients treated across 30+ single center academic trials • Well-tolerated o No (or minimal) CRS, neurotoxicity, GvHD • Anti-tumor activity observed i
Slide 8: Calibrated Release IL-15 Increases Persistence and Activation
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 0 1 2 3 4 5 1 2 3 4 5 6 7 8 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 CAR-NK Cells 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 ) 8 Calibrated Rel
Slide 9: Senti's Next Generation CAR-NK Cell Therapy Pipeline
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S Program Target Indications Discovery IND enabling Phase 1 Gene Circuits SENTI-202 CD33, FLT3 bivalent AML, MDS and other blood cancers ✓ Multi-Arming: designed for enhanced efficacy ✓ crIL-15: autocrine and paracrine activation ✓ OR GATE: bivalen
Slide 10: Manufacturing
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S Manufacturing 10
Slide 11: Scalable Manufacturing to Support Off-The-Shelf CAR-NK Products
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 11 Scalable Manufacturing to Support Off-The-Shelf CAR-NK Products 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 Eng
Slide 12: Senti Selects NK Cell Donors to Support Robust Cell Expansion
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 12 Senti Selects NK Cell Donors to Support Robust Cell Expansion 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
Slide 13: Cryopreservation Process Retains High Potency of CAR-NK Products
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 13 Senti’s Cryopreservation Process Retains High Potency of CAR-NK Products Supporting Multi-Country and Multi-Site Clinical Evaluation 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-
Slide 14: Pipeline Products
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S Pipeline Products 14
Slide 15: SENTI-202 for CD33 and/or FLT3 Expressing Blood Cancers
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 15 SENTI-202 for CD33 and/or FLT3 Expressing Blood Cancers 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 can
Slide 16: SENTI-202 Shows Robust Preclinical Activity Across AML / MDS Models
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 16 SENTI-202 Shows Robust Preclinical Activity Across Multiple AML / MDS Models 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 40
Slide 17: SENTI-202 Preclinical Selectivity via Inhibitory CAR Binding Endomucin
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 17 SENTI-202 Preclinical Selectivity via Inhibitory CAR Binding Endomucin to Protect Healthy Primary Human HSCs In vitro protection of healthy primary human HSC fraction expressing EMCN In vivo protection of EMCN+ model healthy cells Endomucin wa
Slide 18: Proposed Phase 1 Study in R/R CD33+ and/or FLT3+ Malignancies
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 18 Proposed Phase 1 Study in R/R CD33+ and/or FLT3+ Malignancies With Focus on AML Proposed Phase 1 study anticipated to enroll R/R CD33+ and/or FLT3+ heme malignancies • Received at least 1 prior treatment including targeted agents if FLT3, IDH1
Slide 19: SENTI-301A for GPC3 Expressing Solid Tumors
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 19 SENTI-301A for GPC3 Expressing Solid Tumors 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 imm
Slide 20: SENTI-301A Aims to Address Unmet Needs in GPC3 Solid Tumors
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 20 SENTI-301A Aims to Address Unmet Needs in GPC3 Expressing Solid Tumors With a Focus on HCC GPC3 is a validated cancer target • Glypican-3 (GPC3) is a membrane-bound protein normally expressed in fetal tissues such as liver and placenta. • Afte
Slide 21: SENTI-301A Preclinical Activity and Proposed Phase 1 Study
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 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 SENTI-301A Preclinical Anti-Cancer Activity and Proposed Phase 1 Study in Advanced Solid Tumors With Focus on HCC Proposed Phase 1 st
Slide 22: SENTI-401 for CEA Expressing Solid Tumors
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 22 SENTI-401 for CEA Expressing Solid Tumors Multi-Armed, off-the-shelf, selective CAR-NK • CEACAM5 (CEA) activating CAR → colorectal cancer (CRC) and other solid tumors • NOT GATE: inhibition by VSIG2 antigen on healthy epithelial cells → potent
Slide 23: Robust Preclinical Activity With CEA CAR-NK Cells Augmented by Multi-Arming
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 23 Robust Preclinical Activity With CEA CAR-NK Cells That Is Augmented by Multi- Arming With Both crIL-15 and IL-21 0 1 2 3 4 5 1 2 3 4 5 6 N o rm al iz ed T u m o r C el l A re a Days Vehicle CEA CAR-NK Cells CEA CAR-NK Cells + TGFβ crIL15 + IL2
Slide 24: Paired Target and Protective Antigens for SENTI-401
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S Senti’s Approach to Select Paired Target and Protective Antigens Translates to Rapid Preclinical Proof of Principle for SENTI-401 Colorectal cancer CEACAM5 VSIG2 CEACAM5: 85-90% of CRC and 40-60% of other solid tumors including lung cancer1 VSIG2
Slide 25: Discovery Platform for Tumor-Associated and Protective Antigens
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 25 Senti’s Discovery Platform for Tumor-Associated Antigen and Protective Antigen to Generate Many Targets for New Logic Gated CAR-NK Candidates 52 31 Expression in tumor cells A B C 4 Healthy tissue expression of A Expression in tumor cells D E
Slide 26: Gene Circuits Can Vastly Expand the Universe of Cancer Targets
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 26 Gene Circuits Can Vastly Expand the Universe of Cancer Targets and Tumors That Can Be Addressed With Cell Therapies 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
Slide 27: Regulator Dial Enables On-Demand Production of crIL-12
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 27 Senti’s Regulator Dial Enables On-Demand Production of crIL-12 Controlled via Multiple Distinct FDA-Approved Small Molecule Oral Drugs Dose-dependent, reversible crIL-12 controlled by GRZ Vehicle GRZ at 50 mg/kg GRZ at 100 mg/kg 1 10 100 1,000
Slide 28: Platform and Collaboration Opportunities
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S Platform and Collaboration Opportunities 28
Slide 29: Multiple Platform Collaborations Extend Utility of Gene Circuits
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 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 GC-1005 Liver Smart Sensor Cell Therapies for Regenerative Medicin
Slide 30: Two Collaborations to Develop Next Generation Cell and Gene Therapies
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 30 Two Collaborations to Develop Next Generation Cell and Gene Therapies 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 t
Slide 31: Smart Sensor Promoters Address Key Challenges in Gene Therapy
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 31 Smart Sensor Promoters Are Designed to Address Key Challenges in Gene Therapy 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 l
Slide 32: Gene Circuit Technology Has Broad Potential Across Modalities
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 32 Senti’s Gene Circuit Technology Has Broad Potential Across Modalities and Therapeutic Areas Wholly-Owned Programs with Opportunities for Future Development Opportunities for Future Development and Additional Partnering Multi-Arming Logic Gatin
Slide 33: Upcoming Value Driving Milestones
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S Program 2022 Anticipated Milestones 2023 Anticipated Milestones SENTI-202 CD33, FLT3 bivalent AML, MDS and other blood cancers SENTI-301A GPC3 HCC and other solid tumors SENTI-401 CEA CRC and other solid tumors Present data at key scientific conf
Slide 34: Thank you!
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S Thank you! 34
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