Sigilon Therapeutics — Investor Presentation (October 2022)
21 slides from Sigilon Therapeutics's investor presentation, Oct 11, 2022
Slide 1: Pioneering A Cell Therapy Powerhouse
Pioneering A Cell Therapy Powerhouse ©2022 Sigilon Therapeutics, Inc. October 2022
Slide 2: Disclaimer
Disclaimer This presentation has been prepared by Sigilon Therapeutics, Inc. (“we,” “us,” “our,” “Sigilon” or the “Company”) and is made fo r informational purposes only and not for any other purpose. Certain information contained in this presentation and statements made orally during this presentat
Slide 3: Mission: functional cures by harnessing the power of the human cell
MISSION: We aim to deliver functional cures to patients by harnessing the power of the human cell Non - Confidential 3
Slide 4: Strong Foundation to Support Sustained Growth
Strong Foundation to Support Sustained Growth • Seminal work at MIT by Langer & Anderson with the discovery of Afibromer ™ • Sigilon created by Flagship Pioneering (2016) • Lilly partnership for T1D w/ $75M upfront + up to $415M milestones (2018) • NASDAQ: SGTX; IPO $145M (Dec 2020) • FIH in hemophi
Slide 5: Shielded Living Therapeutics (SLTx) Platform
5 Shielded Living Therapeutics ( SLTx ) Platform + + Manufacturing Placement Cells Sphere Non - Confidential
Slide 6: Hem A Phase 1/2 Safety And Dose Ranging Study Update
• No definitive link between SIG - 001 and inhibitors was established • No other tolerability or safety issues • Evidence of sustained FVIII activity was observed at the lowest dose ( 50 mL) for approximately 20 weeks after administration .. • During retrieval procedure, mature localized pericapsula
Slide 7: Building Optimized Cell Therapies: Steps to mitigate PFO risk
8 Building Optimized Cell Therapies: Steps to mitigate PFO risk and optimize Sigilon’s SLTx platform + + Manufacturing Placement Cells Sphere OPTIMIZATION: ❖ iPSC derived cells are less immunogenic than epithelial cells ❖ Exploring lower cell density through higher potency expression ❖ Exploring Imm
Slide 8: Sigilon Encapsulated Drug Product Discovery Process
Sigilon Encapsulated Drug Product Discovery Process Therapeutic concept Protein/Cell engineering Cell Encapsulation Optimization Lead Drug Product Optimization PFO/Efficacy Assessment Tox/PK - PD Assessment First in human • Sequence optimization • Cell line selection • Cell Engineering • Differentia
Slide 9: PFO is a Complex Immunological Process
10 PFO is a Complex Immunological Process N on - Confidential
Slide 10: Developing Allogeneic PFO Prediction Methods
11 Developing Allogeneic PFO Prediction Methods Non - Confidential Macrophage Attachment Assay GO NO - GO huBLT mouse model PFO/Clumping Non - Human Primates Durable PK EXAMPLE 1 day 5 weeks 8 weeks 5 weeks 8 weeks 1 day 5 weeks 8 weeks
Slide 11: Potential PFO Triggers
1) Mediated by Afibromer • Trigger: sphere integrity and stability 2) Mediated by Secretome • Trigger: cell type and density 3) Mediated by Antigens • Trigger: adaptive immunity to specific antigen 12 Potential PFO Triggers Non - Confidential
Slide 12: Prioritized Pipeline
Prioritized Pipeline 13 + Covalent Dual Cross Linking ( dXL ) SIG - 002 iPSC derived Islets Target IND Submission 2024 Diabetes Program Non - Confidential Our Strategic Partner Partnership Overview Lilly’s Financial Commitment • Discover, develop and commercialize encapsulated cell therapy for T1D •
Slide 13: Differentiation Protocol Optimization Produces SC-islets with Improved Profiles
14 Differentiation Protocol Optimization Produces SC - islets with Improved Cell Profiles and Potency iPSC Mesendoderm Stage 1 Definitive Endoderm Stage 1 Primitive Gut Tube Stage 2 Foregut Endoderm Stage 3 Pancreatic Progenitors Stage 4 Pancreatic Endocrine Precursors Stage 5 Islets Immature Beta C
Slide 14: SIG-Spheres with SC-islets are Efficacious in Immune-Deficient Diabetic Mice
15 SIG - 002 Spheres with SC - islets are Efficacious in Immune - Deficient Diabetic Mice Non - Confidential 0 30 60 90 120 0 200 400 600 800 SG-VIVO7966-1 D70 Oral Glucose Tolerance Test Time (min) Blood Glucose (mg/dL)
Slide 15: Pipeline Prioritization: Expanded MPS-1 Program
Pipeline Prioritization 16 SIG - 105 Expanded MPS - 1 Program SIG - 105 ARPE - 19 - LSD 2.0 (CNS targeting) + Covalent Dual Cross Linking ( dXL ) ImmunoQuiet * ARPE - 19 LSD 2.0 SIG - 205 + Covalent Dual Cross Linking ( dXL ) ImmunoQuiet (CNS targeting) Non - Confidential • SOC (enzyme replacement t
Slide 16: Reduction of Substrate in Tissues of MPSI-H Mice After SIG-005
Reduction of Substrate in Tissues of MPSI - H Mice 6 Months After SIG - 005 17 Untreated MPSI - H SIG - 005 * * * * * * * * * * * * 10x 10x 10x 10x 10x 10x 10x 10x 40x 40x 40x 40x 40x 40x 40x 40x MPS - 1: mucopolysaccharidosis type I; Images taken by NanoZoomer S60 with 20x Representative images tak
Slide 17: SIG-005: Phenotypic Correction in Bone in Mice With MPS-1
18 SIG - 005: Phenotypic Correction in Bone After 6 Months of Treatment in Mice With MPS - 1 Distal Femur – Sagittal View of Trabecular Areas Untreated MPS - 1H SIG - 005 Treated M F M F Untreated MPS - 1H SIG - 005 - treated Laronidase - treated F M F M F M Laronidase Treated M F Zygomatic Arch – T
Slide 18: Expanded MPS-1 Program Will Enable Blood Brain Barrier Penetration
Expanded MPS - 1 Program Will Enable Blood Brain Barrier Penetration BBB - penetrant Camelid HCAb BBB V H H Cargo Protein Half - life V H H Half - life extending Camelid HCAb VH + - 32% Technology Details Good systemic tissue penetration and functional activity towards target substrate Total Heparan
Slide 19: Manufacturing Strategy – Long-Term Improvements to Enable Off-the-Shelf Allogeneic Products
20 Manufacturing Strategy – Long - Term Improvements to Enable Off - the - Shelf Allogeneic Products Non - Confidential • Scale up drug substance manufacturing • Automate and scale up drug product manufacturing • Develop cryopreserved drug product
Slide 20: Future Expansion Strategy
• Acute • Chronic • CNS • Immune mediated Diseases (IMD) • Liver Diseases • Immuno - oncology Multiple Cell Lines Existing Technologies & Capabilities Allowing for the exploration of a broad range of indications, including: *Future Cells Source Future Expansion Strategy Non - Confidential Vision to
Slide 21: Upcoming Milestones
22 Upcoming Milestones • H2 2023: initiate IND - enabling studies for Type 1 Diabetes program with optimized spheres • H2 2023: initiate IND - enabling studies for Expanded MPS - 1 Program • Continued pipeline expansion • IND for Type 1 Diabetes • IND for Expanded MPS - 1 Program • IND enabling stud
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