Sigilon Therapeutics — Investor Presentation (March 2022)
28 slides from Sigilon Therapeutics's investor presentation, Mar 14, 2022
Slide 1: Pioneering a New Class of Allogeneic Cell Therapy
Pioneering a New Class of Allogeneic Cell Therapy ©2022 Sigilon Therapeutics, Inc. March 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
2 MISSION: Harnessing the power of the human cell, we aim to deliver functional cures to patients with a broad range of chronic diseases
Slide 4: Modular SLTx Product Platform
Modular SLTx Product Platform Manufacturing Placement Cells + Sphere 3 Spheres delivered to peritoneal space through interventional r adiology under local anesthesia Growing Intellectual Property Portfolio – 27 patent families; >96 pending applications in major markets
Slide 5: Shielded Living Therapeutics (SLTx), a Non-Viral Engineered Cell-Based Therapy
4 Shielded Living Therapeutics ( SLTx ), a Non - Viral Engineered Cell - Based Therapy Host genome unaltered 1 Shielded allogeneic cells 2 Redosable , retrievable and t itratable 3 Multiple tissue applicability 4 Established GMP manufacturing 5 Potential Attributes
Slide 6: Strong Foundation to Support Sustained Growth
Strong Foundation to Support Sustained Growth 5 2018 – 2019 Applying lessons learned to next programs Seminal work at MIT by Langer & Anderson with the discovery of Afibromer ™ Sigilon created by Flagship Pioneering (2016) Developed our modular platform IPO $145M (Dec 2020) Lilly partnership for T1D
Slide 7: Clinical & Pipeline Update
Clinical & Pipeline Update Phase 1/2 Hemophilia A Trial Update: • Three patients dosed (UK & U.S.) • Dose range: 300 million to 1 billion cells • One patient experienced SAE (inhibitor development) and spheres with PFO (pericapsular fibrotic overgrowth) • Established GMP manufacturing and logistics
Slide 8: Leaders with a Proven Track Record of Driving Value
Non - Confidential 7 Industry Leaders with a Proven Track Record of Driving Value Rogerio Vivaldi, MD, MBA President, Chief Executive Officer Olivia Kelly, PhD S VP, Head of Diabetes Research Matthew Kowalsky , JD Chief Legal and Administrative Officer Rogerio Vivaldi, MD, MBA S i g i l o n T h e r
Slide 9: Preclinical Program Overview
Preclinical Program Overview ✓ 28 - day NHP PK (SIG - 001 & SIG - 005) study confirmed bioavailability in plasma with relevant levels ✓ Multiple rodent studies in Hem A and MPS - 1, provided evidence on bioavailability in plasma and target organs BIOAVAILABILITY FROM IP → PLASMA ✓ Product delivery m
Slide 10: Addressing a Broad Range of Chronic Diseases
Addressing a Broad Range of Chronic Diseases 9 PRIORITIZED AREAS OF DEVELOPMENT PROGRAM CELL PRODUCT RESEARCH & DISCOVERY LEAD OPTIMIZATION PRECLINICAL DEVELOPMENT PHASE 1/2 PHASE 3 SIG - 005: MPS - 1 Human IDUA SIG - 002: T1 Diabetes Human Insulin EXPANSION AREAS OF DEVELOPMENT PROGRAM CELL PRODUCT
Slide 11: SLTx Potential to Treat Lysosomal Diseases
SLTx Potential to Treat Lysosomal Diseases • SOC (enzyme replacement therapy) requires life - long weekly administration and can be hampered by a short enzyme half - life • Our SLTx platform offers the potential for sustained substrate reduction (vs. peaks and troughs) • Preclinically demonstrated e
Slide 12: MPS-1 Overview
11 MPS - 1 Overview MPS - 1: a rare genetic disease caused by a deficiency of IDUA enzyme that results in the accumulation of GAGs within cells affects many body systems and leads to organ damage ~1 in 100,000 live births enzyme replacement therapy (ERT) and bone marrow transplantation (BMT) for Hur
Slide 13: SIG-005 Produced Active hIDUA In Vitro and In Vivo for at Least 6 Months
12 SIG - 005 Produced Active hIDUA Both In Vitro and In Vivo for at Least 6 Months 0 4 8 12 16 20 24 0 2 4 6 Weeks, in vitro U/sphere/hour SIG - 005: Consistent levels of hIDUA produced from spheres for 6 - months in vitro SIG - 005: Low levels of HS in plasma 6 - months post - administration in MPS
Slide 14: Reduction of Substrate in Tissues of MPS-1H Mice
Reduction of Substrate in Tissues of MPSI - H Mice 6 Months After SIG - 005c 13 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 ta
Slide 15: SIG-005: Corrected Bone Phenotype in MPS-1H Mice 6 Months After Administration
14 MPS-1 Untreated SIG-005 HET 0 1 2 3 Zygomatic TV (mm3) ✱✱✱✱ Total Bone Volume (Zygomatic Arch) Bone Length (Femur) MPS-1 Untreated SIG-005 HET 13 14 15 16 17 Femur length (mm) ✱✱ Cortical Thickness (Femur Midshaft) Trabecular Bone Volume (Distal Femur) MPS-1 Untreated SIG-005 HET 0.10 0.15 0.20 0
Slide 16: SIG-005: Phenotypic Correction in Bone in Mice With MPS-1
15 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 17: Non-Cryopreserved Drug Substance Expected to Decrease Manufacturing Lead Times
Non - Confidential 16 Cryopreserved Drug Substance Expected to Decrease Manufacturing Lead Times for SIG - 005 by 80% Thaw Drug Substance Encapsulation Cell Expansion & Cryopreservation ~4 Weeks Up to 300mL Pooled SIG - 005 Final Filled DP SIG - 005 QC Release Testing Bulk Drug Product (DP) ~1 week
Slide 18: Developed Interventional Radiology Guided Sphere Delivery
17 Developed Interventional Radiology (IR) Guided Sphere Delivery • No insufflation • Under local anesthesia only • Single incision • Closed delivery system from product bag • Insufflation • Under general anesthesia • 2 port incision Laparoscopic Surgery Interventional Radiology Guided Placement Lys
Slide 19: SIG-005: Clinical Development in MPS-1
SIG - 005: Clinical Development in MPS - 1 Non - Confidential Lysosomal Diseases Clinical Trial Preparation Submit CTA (UK & Brazil) amendment submission for SIG - 005 in MPS - 1 in 2H 2022 Serial Imaging Inflammatory biomarkers Inclusion/Exclusion Criteria PK measurements PFO Mitigation regimen 1 2
Slide 20: Type 1 Diabetes Overview
19 Type 1 Diabetes Overview T1D: ~1.6 M patients in the U.S. treatment focuses on managing blood sugar levels with exogenous insulin, diet and lifestyle to prevent complications SOC includes Unmet medical need includes Non - Confidential impaired awareness of hypoglycemia (IAH) even with CGM subopti
Slide 21: Lilly Collaboration to Develop a Potential Functional Cure for Type 1 Diabetes
Non - Confidential 20 Lilly Collaboration to Develop a Potential Functional Cure for Type 1 Diabetes • Discover, develop and commercialize encapsulated cell therapy for T1D • Sigilon will create proprietary products and develop through IND • Eli Lilly responsible for clinical development and commerc
Slide 22: Functional Cure for Type 1 Diabetes: Insulin Independence Without Immunosuppression
21 Non - Confidential Functional Cure for Type 1 Diabetes Insulin Independence Without Immunosuppression Sneddon et al 2018 Cell Stem Cell 22:810 - 823 Iworima et al 2021 Stem Cells Transl. Med. 1 - 11 SIG - 002: Sigilon Spheres with iPSC - Islets Islet Cell Therapy Directed Differentiation of iPSC
Slide 23: Durable Glucose Control in Preclinical Models
22 Sigilon Technology Demonstrates Durable Glucose Control in Preclinical Models Review Article by Langer R; Molecular Frontiers Journal (2017) Encapsulated Rat Donor Islets in Diabetic Mice Encapsulated Cadaveric Human Islets in Diabetic Mice 60 0 50 0 40 0 30 0 Time (Days) 600 500 400 300 200 100
Slide 24: Expansion Areas of Development: Crossing the Brain Barrier
Expansion Areas Of Development Crossing The Brain Barrier - BBB - hIDUA BBB - penetrant Camelid HCAb BBB V H H Cargo Protein Half - life V H H Half - life extending Camelid HCAb VH + - 32% Technology Details Expansion Good systemic tissue penetration and functional activity towards target substrate
Slide 25: Expansion Areas of Development: Developing Products for Liver Diseases
Saline ConA 3T3 mIL-10 + ConA 0 2 4 6 Liver Score 24 Expansion Areas Of Development Developing Products for Liver Diseases Liver Necrosis Saline Concanavalin A ( ConA ) mIL - 22 spheres + ConA SLTx - IL - 10 SLTx - IL - 22 Saline Concanavalin A (ConA) mIL - 10 spheres + ConA Hepatocyte Necrosis Sali
Slide 26: Multiple Milestones Targeted within 2022 and 2023
25 Multiple Milestones Targeted within 18 months H2 22 • Results of preclinical studies designed to evaluate PFO and mitigation strategies in humanized mice and non - human primates • CTA (UK & Brazil) amendment submission for SIG - 005 in MPS - 1 2023 • Phase 1/2 Initiation: SIG - 005 in MPS - 1 •
Slide 27: Strong Foundation to Support Sustained Growth
Strong Foundation to Support Sustained Growth 26 2018 – 2019 Applying lessons learned to next programs Seminal work at MIT by Langer & Anderson with the discovery of Afibromer ™ Sigilon created by Flagship Pioneering (2016) Developed our modular platform IPO $145M (Dec 2020) Ongoing manufacturing pl
Slide 28: Thank You
Thank You Contact Us: Robert Windsor, Jr., J.D. VP, Head of Investor Relations, Sigilon Therapeutics Robert.windsor@sigilon.com 617.586.3837
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