Sigilon Therapeutics — Corporate Update (November 2022)
29 slides from Sigilon Therapeutics's corporate update, Nov 10, 2022
Slide 1: Pioneering A Cell Therapy Powerhouse
Pioneering A Cell Therapy Powerhouse ©2022 Sigilon Therapeutics, Inc. November 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: deliver 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 3 Non - Confidential
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: Industry Leaders with a Proven Track Record of Driving Value
Industry Leaders with a Proven Track Record of Driving Value Non - Confidential Rogerio Vivaldi, MD, MBA President, Chief Executive Officer Matthew Kowalsky , JD Chief Legal & Administrative Officer Rogerio Vivaldi, MD, MBA CEO S i g i l o n T h e r ap e u t i c s Robert Ruffolo, Jr., PhD Former Hea
Slide 7: 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 pericapsular f
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
9 PFO is a Complex Immunological Process Non - Confidential
Slide 10: Building Optimized Cell Therapies: Steps to mitigate PFO risk
10 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 Im
Slide 11: Developed Allogeneic PFO Prediction Methods
Developed 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 11
Slide 12: Potential PFO Triggers
1) External surface of sphere • Macrophage attachment 2) Secretome • Inflammatory stimulation 3) Antigens • Adaptive Immunity to specific antigen activation Potential PFO Triggers Non - Confidential 12
Slide 13: Dual Crosslinking (dXL) Alginate Stabilized Afibromer and Spheres
Dual Crosslinking ( dXL ) Alginate Stabilized Afibromer a nd Spheres In Vivo in Preclinical Studies D0 D28 D56 D84 0 50 100 Afibromer Stability with dXL 7 % Afibromer relative to D0 • Stabilizes spheres • Minimizes Ba 2+ content • Supports cell viability and productivity • Maintains potency • Improv
Slide 14: Potential PFO Triggers
1) External surface of sphere • Macrophage attachment 2) Secretome • Inflammatory stimulation 3) Antigens • Adaptive Immunity to specific antigen activation Potential PFO Triggers Non - Confidential 14
Slide 15: No Evidence of PFO for SIG-002 in Allogeneic hu-BLT Mice
No Evidence of PFO for SIG - 002 in Allogeneic hu - BLT Mice SIG-000 iXL SG1 SIG-005 25M iXL SG1 SIG-005 25M dXL SG1 SIG-002 dXL SG1 Polystyrene Beads 0 100 200 300 400 500 1000 1500 PFO Response at Day 35 (huBLT model) Total Weight of Clumped Spheres (mg) Clumps No Clumps We expect that SIG - 002 w
Slide 16: Potential PFO Triggers
1) External surface of sphere • Macrophage attachment 2) Secretome • Inflammatory stimulation 3) Antigens • Adaptive Immunity to specific antigen activation Potential PFO Triggers Non - Confidential 16
Slide 17: Inhibition of Adaptive Immunity Improves PK of SIG-005
• SIG - 005 non - toxic and well tolerated in NHP study • Edmonton protocol reduced antibodies to encapsulated cells & improved pharmacokinetic profile of SIG - 005, even in iXL spheres • Results corroborate current dosing assumptions Inhibition of Adaptive Immunity Improves PK of SIG - 005 Edmonton
Slide 18: SLTx Encapsulation May Have Significant Advantages Over Naked Cell Therapies
SLTx Encapsulation May Have Significant Advantages Over Naked Cell Therapies SLTx PLATFORM – POTENTIAL ADVANTAGES • No antibody - m ediated c ytotoxicity • Known b iology and IP landscape • Minimal gene edits to reduce risk of off - target effects • Designed to block antibody and immune cell infiltr
Slide 19: Prioritized Pipeline
PROGRAM CELL PRODUCT/TYPE DISCOVERY LEAD OPTIMIZATION IND ENABLING PHASE 1/2 Prioritized Programs SIG - 002 – Type 1 Diabetes Insulin & others SIG - 105/205 – CNS MPS - 1 BBB - Human IDUA Lysosomal Diseases SIG - 207 – CNS Fabry BBB - Human GLA SIG - 218 – CNS MPS - 2 BBB - Human IDS SIG - 220 – MPS
Slide 20: Diabetes Program and Lilly Partnership
Diabetes Program 20 + Covalent Dual Cross Linking ( dXL ) SIG - 002 iPSC derived Islets Target IND Submission H2 2024 Non - Confidential Our Strategic Partner Partnership Overview Lilly’s Financial Commitment • Discover, develop and commercialize encapsulated cell therapy for T1D • Sigilon will crea
Slide 21: Differentiation Protocol Optimization Produces SC-islets with Improved Profiles
21 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 22: SIG-002: Efficacious in Immune-Deficient Diabetic Mice
22 SIG - 002: Efficacious in Immune - Deficient Diabetic Mice 10 weeks after implantation 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 23: Expanded MPS-1 Program
Expanded MPS - 1 Program 23 SIG - 105 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 therapy) requires life -
Slide 24: SIG-005: Reduction of Substrate in Tissues in MPS-1 Mice
SIG - 005: Reduction of Substrate in Tissues After 6 Months of Treatment in Mice With MPS - 1 24 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 Represe
Slide 25: SIG-005: Phenotypic Correction in Bone in MPS-1 Mice
25 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 26: 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 27: Manufacturing Strategy – Long-Term Improvements for Off-the-Shelf Products
27 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 28: 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 29: Upcoming Milestones
29 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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