Senti Biosciences Holdings, Inc. · NASDAQ:SNTI
Senti Biosciences — Investor Presentation (October 2022)
30 slides from Senti Biosciences's investor presentation, Oct 3, 2022
Slide 1: Corporate Presentation October 2022
O C T O B E R 2 0 2 2 | SE N T I B IO SC IE N C E S Corporate Presentation 1 October 2022 ™
Slide 2: Disclaimer: Forward Looking Statements
O C T O 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 S
Slide 3: Pioneering Smarter Next Generation Cell and Gene Therapies
O C T O 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 therapy
Slide 4: Industry-Leading Management With Top-Tier Board and Scientific Advisors
O C T O 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 Fussene
Slide 5: CAR-NK Cell Therapy Pipeline
O C T O 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
O C T O 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 tox
Slide 7: NK Cells Have Compared Favorably to Current Approved T Cell Therapies
O C T O 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 in
Slide 8: Calibrated Release IL-15 (crIL-15)
O C T O B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 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 Release IL-15 (crIL-15) Increased Persistence and Activation of Both CAR-NK and Immune Cells in Tumor Milieu Phospho STAT5 levels increased i
Slide 9: Senti's Next Generation CAR-NK Cell Therapy Pipeline Tackles Hard to Treat Cancers
O C T O 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: bivalent
Slide 10: Manufacturing
O C T O 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 Products
O C T O 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 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 Engineer Cry
Slide 12: Senti Selects NK Cell Donors to Support Robust Cell Expansion
O C T O 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 30
Slide 13: Cryopreservation Process Retains High Potency of CAR-NK Products
O C T O 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-th
Slide 14: Pipeline Products
O C T O 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
O C T O 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 cance
Slide 16: SENTI-202 Shows Robust Preclinical Activity
O C T O 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 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 50 60 70 80 90 100 Blasts LSCs Bla
Slide 17: SENTI-202 Preclinical Selectivity via Inhibitory CAR Binding Endomucin
O C T O 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 on Healthy Primary Human Hematopoietic Stem Cells (HSCs) In vitro protection of healthy primary human HSC fraction expressing EMCN In vivo protection of EMCN+ model healthy c
Slide 18: Proposed Phase 1 Study in R/R CD33+ and/or FLT3+ Malignancies
O C T O 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, IDH1/2
Slide 19: SENTI-301 for GPC3 Expressing Solid Tumors
O C T O B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 19 SENTI-301 for GPC3 Expressing Solid Tumors Multi-Armed, off-the-shelf, Regulator Dial controlled CAR-NK • GPC3 activating CAR → hepatocellular carcinoma (HCC) and other solid tumors • crIL-15 → potential for increased persistence, autocrine and
Slide 20: SENTI-301 Preclinical Anti-Cancer Activity
O C T O B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 0 20 40 60 80 100 0 20 40 60 80 100P ro b ab ili ty o f Su rv iv al Days Post Tumor Implantation Vehicle Unengineered NK Cells crIL-15 GPC3 CAR-NK Cells 20 crIL-15 GPC3 CAR-NK Cells Preclinical Anti-Cancer Activity Group Tumor Cells Unengineered NK
Slide 21: Regulator Dial Enables On-Demand Production of crIL-12
O C T O B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 21 1 10 100 1,000 10,000 100,000 0 mg/kg 50 mg/kg 100 mg/kg 0 mg/kg 50 mg/kg 100 mg/kg 0 mg/kg 50 mg/kg 100 mg/kg cr IL -1 2 ( p g /m L) Day 2 (GRZ ON) Day 9 (GRZ OFF) Day 11 (GRZ ON) Drug Drug Drug 1 Leonard 1997 crIL-12 release controlled by smal
Slide 22: SENTI-401 for CEA Expressing Solid Tumors
O C T O 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 → potentia
Slide 23: Approach to Select Paired Target and Protective Antigens
O C T O B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 23 Senti’s Approach to Select Paired Target and Protective Antigens Translates to Rapid Preclinical Proof of Principle 0 1 2 3 4 5 6 7 8 9 10 0 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 CEA CAR-NK Ce
Slide 24: Platform Collaborations
O C T O B E R 2 0 2 2 | SE N T I B IO SC IE N C E S Platform Collaborations 24
Slide 25: Multiple Platform Collaborations Extend Utility of Gene Circuits
O C T O 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 Medicine
Slide 26: Two Collaborations to Develop Next Generation Cell and Gene Therapies
O C T O B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 26 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 the
Slide 27: Smart Sensor Promoters Address Key Challenges in Gene Therapy
O C T O B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 27 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 lin
Slide 28: Gene Circuit Technology Has Broad Potential Across Modalities and Therapeutic Areas
O C T O B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 28 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 Gating
Slide 29: Upcoming Value Driving Milestones
O C T O 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-301 GPC3 HCC and other solid tumors SENTI-401 CEA CRC and other solid tumors Present data at key scientific confere
Slide 30: Thank you!
O C T O B E R 2 0 2 2 | SE N T I B IO SC IE N C E S Thank you! 30
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