Sigilon Therapeutics — Investor Presentation (March 2023)
24 slides from Sigilon Therapeutics's investor presentation, Mar 14, 2023
Slide 1: Leading the Next Frontier of Allogeneic Cell Therapy
©2023 Sigilon Therapeutics, Inc. March 2023 Leading the Next Frontier of Allogeneic Cell Therapy
Slide 2: Forward-looking statements
Forward-looking statements This presentation has been prepared by Sigilon Therapeutics, Inc. (“we,” “us,” “our,” “Sigilon” or the “Company”) and contains forward-looking statements. All statements other than statements of historical facts contained in this presentation are forward-looking statements
Slide 3: Mission: functional cures by harnessing the power of the human cell
M I S S I O N : 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 Company Background Our Potential Attributes 1 No chronic immune suppression 2 Sense and respond to disease 3 Retrievable and redosable 4 Safe & Durable Scalable to tackle high cell counts 5 Non-Confidential o Seminal work at MIT by Langer & Anderson with
Slide 5: Industry leaders with a proven track record of creating value
Industry leaders with a proven track record of creating value Rogerio Vivaldi, MD, MBA President, Chief Executive Officer Olivia Kelly, PhD SVP, Head of Diabetes Research Matthew Kowalsky, JD Chief of Staff; Chief Legal & Administrative Officer Rogerio Vivaldi, MD, MBA Sigilon Therapeutics Robert Ru
Slide 6: 40+ year journey in search of sustainable cell therapies
40+ year journey in search of sustainable cell therapies Lim et al. Science Vol 210 p908 1980 Fibrosis Immediate Immune Response 6 Lim et al. Science Vol 210 p908 1980 Main Challenges ➢ Immune rejection ➢ Poor Engraftment ➢ Prohibitive Cost Non-Confidential 6
Slide 7: Optimized Product Key Learnings Guide Our Approach
Optimized Product 7 Key Learnings Guide Our Approach KEY REQUIREMENTS No chronic immunosuppression Exposure control Safe Scalable, with acceptable costs Appropriate indications Non-Confidential
Slide 8: Platform Strategy: broad range of indications across multiple cell lines
Allowing for the exploration of a broad range of indications, including acute and chronic, rare and prevalent disease Multiple Cell Lines Existing Technologies & Capabilities Right Indication Platform Strategy Vision to become cell therapy powerhouse, leveraging encapsulation platform and manufactur
Slide 9: Novel approach to de-risk programs
Novel approach to de-risk programs Immunogenicity is one of the critical barriers to allogeneic cell therapy Therapeutic concept Powerful, Precision Proprietary Cell Differentiation Proprietary models to predict and prevent immunogenicity 9 61% % of Beta cells In-vitro MA Assay PFO & Clumps In-vivo
Slide 10: Leading to scalable & cost-effective manufacturing
Leading to scalable & cost-effective manufacturing Product Optimization Tox/PK-PD Characterization • Mice / NHP • PK/PD 10 0 10 20 30 40 50 60 70 80 90 100 110 120 0 200 400 600 800 SG-VIVO8018-1 E217 Blood Glucose Levels Time (days) Blood Glucose (mg/dL) GMP Manufacturing FIH Encapsulation Off the
Slide 11: Ongoing Optimization
Ongoing Optimization Mitigating the risks of PFO and optimize SLTx platform + + Cells Sphere Manufacturing Placement O P T I M I Z A T I O N : ❖ iPSC derived cells are less immunogenic than epithelial cells ❖ Exploring lower cell density through higher potency expression ❖ Exploring ImmunoQuiet cell
Slide 12: PFO is a Complex Immunological Process
PFO is a Complex Immunological Process Non-Confidential 12
Slide 13: New Assays and Experiments to Assess PFO
Non-Confidential SIG-000 (No Cells) SIG-005 SIG-002 Polystyrene Beads SIG-0SIG-0 5 SIG-0 2 Polystyrene Beads 0 50 100 150 200 500 1000 1500PFO Response at Day 35 (huBLT model) Total Weight of Clumped Spheres (mg) Clumps No Clumps PFO in Humanized BLT mouse model SIG-000: No cells SIG-005: ARPE cells
Slide 14: Pipeline
PROGRAM CELL PRODUCT/TYPE DISCOVERY LEAD OPTIMIZATION IND ENABLING PHASE 1/2 SIG-002 – Type 1 Diabetes Human Insulin Lysosomal Diseases SIG-205 – CNS MPS-1 BBB-Human IDUA SIG-207 – Fabry Human GLA SIG-218 – CNS MPS-2 BBB-Human IDS SIG-220 – MPS-6 Human ARSB Liver Diseases SIG-XXX – Undisclosed ApoL-
Slide 15: Our Diabetes Program and Strategic Partner Lilly
Mechanism Maintain blood glucose level by sensing and responding to glucose excursions Recapitulate pancreas function Insulin independence from exogenous insulin without immunosuppression Non-Confidential 15 Our Strategic Partner Glucose Insulin Glucagon Afibromer™ Encapsulation • $75 million up fro
Slide 16: SIG-002: Sigilon Spheres with iPSC-Islets
16 Non-Confidential Directed Differentiation of iPSC to Islets Sneddon et al 2018 Cell Stem Cell 22:810- 823 Iworima et al 2021 Stem Cells Transl. Med. 1-11 Islet Cell Therapy SIG-002: Sigilon Spheres with iPSC-Islets Functional Cure for Type 1 Diabetes Insulin Independence Without Immunosuppression
Slide 17: SC-islets compare favorably to human islets
Non-Confidential Brissova et al 2005 Human Islets beta 0 20 40 60 80 100 Islet Cell Population (%) (61%) SC-islets Sigilon Human Islets (n=17) SC-Islets (n=13) 0 400 800 1200 Insulin Content nU/cell Dynamic Insulin Secretion SC-islets (n=6): 70±31 pU/cell/min average peak at high glucose Our SC-isle
Slide 18: SIG-002 is efficacious and durable in immune-deficient diabetic mice
18 Non-Confidential 0 30 60 90 120 0 200 400 600 800 SG-VIVO7966-1 Day 70 Oral Glucose Tolerance Test Time (min) Blood Glucose (mg/dL) 0 10 20 30 40 50 60 70 80 90 100 110 120 0 200 400 600 800 SG-VIVO8307-1 Blood Glucose Time (days) Blood Glucose (mg/dL) SIG-002 is efficacious and durable in immune
Slide 19: SLTx Encapsulation May Have Significant Advantages Over Hypoimmune Approaches
SLTx Encapsulation May Have Significant Advantages Over Hypoimmune Approaches SLTx PLATFORM – POTENTIAL ADVANTAGES • No antibody-mediated cytotoxicity • Known biology and IP landscape • Minimal gene edits to reduce risk of off-target effects • Designed to block antibody and immune cell infiltration,
Slide 20: Designing Product Candidates for Lysosomal Diseases to Enable BBB Penetration
Designing Product Candidates for Lysosomal Diseases to Enable Blood Brain Barrier Penetration BBB-penetrant Camelid HCAb BBB VHH Cargo Protein Half-life VHH Half-life extending Camelid HCAb VH + - 32% Technology Details Good systemic tissue penetration and functional activity towards target substrat
Slide 21: Manufacture Anytime
M ANU F A C T U R E ANY T I M E 4 W E E K S 21 Non-Confidential Full Release Differentiation Filled DS Cryopreservation WCB Thaw Staged Release DS Thaw Encapsulation Thaw Drug Substance Encapsulation Cell Expansion & Cryopreservation ~4 Weeks Up to 300mL Pooled SIG-005 Final Filled DP SIG-005 QC Rel
Slide 22: Manufacturing strategy to enable off-the-shelf products
Stem Cell Differentiation Drug Product Cryopreservation Hospital Pharmacy Patients 22 Non-Confidential • Scale up drug substance manufacturing • Automate and scale up drug product manufacturing • Develop cryopreserved drug product Off the Shelf Drug Product On-demand Administration Campaigned Produc
Slide 23: Upcoming expected milestones
23 Upcoming expected milestones 1. Initiate IND-enabling studies for Type 1 Diabetes with optimized spheres 2. In vivo PoC / PFO models (including first of its kind NHP study) 1. Completion of IND-enabling studies for Type 1 Diabetes 2. IND for Type 1 Diabetes 3. Lead optimization for 3 - 4 new targ
Slide 24: Thank you
sigilon therapeutics” Thank you
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