Slide 1: CNTY-813: Scalable Production of Allo-Evasion 5.0-Engineered iPSC Islets
CNTY-813: Scalable Production of Allo-Evasion 5.0- Engineered iPSC Islets for Off-the-Shelf Cell Therapies Leonardo Velazco-Cruz, PhD
Slide 2: Disclosures
2 • Presenter – Leonardo Velazco-Cruz, PhD • Relevant Financial Relationship – Employee, Century Therapeutics – Stock/Shareholder: Century Therapeutics • Presentation Information: – This presentation describes preclinical research related to CNTY-813, an investigational iPSC-derived islet cell thera
Slide 3: Forward-looking statements
3 Forward-looking statements This presentation contains forward-looking statements within the meaning of, and made pursuant to the safe harbor provisions of, The Private Securities Litigation Reform Act of 1995. All statements contained in this presentation, other than statements of historical facts
Slide 4: Islet cell transplantation provides potential for curative therapy in T1D
4 Islet cell transplantation provides potential for curative therapy in T1D In T1D, beta cells are destroyed Healthy beta cells produce insulin (green) In T1D, beta cells are destroyed Insulin independence following pancreatic islet transplantation 1. Approximately 1500 patients reported in https://
Slide 5: Scalable manufacturing, islet function, and immune-evasive engineering address key barriers
5 Scalable manufacturing, islet function, and immune-evasive engineering address key barriers for T1D cell replacement DIFFERENTIATION PLATFORM • Scalable iPSC-derived islet manufacturing • Reproducible islet differentiation • Clinical manufacturing process from GMP MCB CNTY-813 design integrates ke
Slide 6: Differentiation process adapted to a scalable bioreactor suspension system
6 • Dotted lines: success criteria • N are independent batches. • Source: Company data on file Defined, Multi-stage Bioreactor Enabled Differentiation Process Adapted to a Scalable Bioreactor Suspension System iPSC Definitive Endoderm Primitive Gut Tube Pancreatic Progenitor I Pancreatic Progenitor
Slide 7: Phase 1 clinical manufacturing process established across 3 independent batches
7 4X 300um CONFIDENTIAL Endocrine Purity Beta Cell Content Islet Cell Impurity • 3 Batches • 11 Samples Phase 1 clinical manufacturing process established and executed from MCB across 3 independent batches MCB Thaw → iPSC Expansion → Bioreactor Differentiation → Cryopreserved Intermediate → Post-Tha
Slide 8: CNTY-813 islet cells demonstrate robust glucose-responsive function
8 CNTY-813 islet cells demonstrate robust glucose-responsive function Potency Glucose Stimulated Insulin Secretion Stimulation Index Total Insulin Content iPSC- Islets Primary Islets 0 5 10 15 Glucose Stimualtion Index (20mM glucose/ 2mM glucose) Mean +/- SD is shown in graphs iPSC- Islets Primary I
Slide 9: CNTY-813 islets rapidly restored normoglycemia in STZ-induced diabetic mice
9 CNTY-813 islets rapidly restored normoglycemia in STZ-induced diabetic mice Allo-Evasion 5.0-edited CNTY-813 restored glucose control comparable to unedited islets and persists for >8 months Potency Non-Fasted Blood Glucose STZ = Streptozotocin | SRC = Sub renal capsule implantation, Gray shaded a
Slide 10: CNTY-813 islets contain defined endocrine cell populations
10 CNTY-813 islets contain defined endocrine cell populations Population (30,151 total) Frequency β cells: 66.3% FEV+ Islet Cells 26.4% ⍺ cells 5.5% δ cells 0.8% Exocrine/Ductal 1.0% CNTY-813 data represents four combined end-of-process samples Population Enriched Markers: β-cell: INS, NKX6.1; ⍺-cel
Slide 11: CNTY-813 grafts maintain endocrine identity with no evidence of tumorigenesis
11 CNTY-813 grafts maintain endocrine identity with no evidence of tumorigenesis 2 weeks INS+ (green) CHGA+ (orange) Merged (yellow) 4 weeks 8 weeks Ki67+ (pinK) DAPI (blue) Endocrine graft identity over time ✓ Endocrine graft morphology maintained through 8 weeks ✓ No Ki67 increase or cyst formatio
Slide 12: CNTY-813 is engineered to evade T cell, NK cell, and humoral responses
12 CNTY-813 is engineered to evade T cell, NK cell, and humoral responses Protection from: T cells NK cells Humoral Immunity Deletion of HLA-I Deletion of HLA-II Insertion of CD300a TASR pan-NK inhibitory ligand1, 2 Insertion of cell-surface enzyme to degrade IgG antibodies3 1. https://www.centurytx
Slide 13: CNTY-813 demonstrated protection from multiple immune effector mechanisms
13 CNTY-813 demonstrated protection from multiple immune effector mechanisms 1. NK-CELL PROTECTION 2. IgG CLEAVAGE 3. PROTECTED FROM PHAGOCYTOSIS Reduced NK Cell Activation Reduced NK Cell Cytotoxicity Rapid IgG Cleavage Reduced Antibody-Dependent Phagocytosis (ADCP) Significant reduction in intact
Slide 14: Employing a humanized mouse model to study allogeneic graft rejection
14 Employing a humanized mouse model to study allogeneic graft rejection d Humanized Mouse Engrafted with Healthy Donor PBMCs • Functional human T cells without GvHD (MHC DKO) – supports longer study durations • Supports engraftment and survival of human NK cells (TgHu-IL15) • Testing of allo-reject
Slide 15: Allo-evasion 5.0 maintains CNTY-813 Glucose Stimulated Insulin Secretion
15 Allo-evasion 5.0 maintains CNTY-813 Glucose Stimulated Insulin Secretion Allo-Evasion 5.0 protected CNTY-813 from rejection in humanized mice 0 7 14 21 28 35 42 49 0 5 10 15 Days Post Transplant Glucose-Stimulated Insulin Secretion Index (C-peptide induction over baseline) Unedited Islets + PBMCs
Slide 16: Allo-evasion 5.0 maintained CNTY-813 GTT performance
16 Allo-evasion 5.0 maintained CNTY-813 GTT performance 0 30 60 90 120 0 200 400 600 Time (min.) Blood Glucose (mg/dL) Unedited Islets + PBMCs Unedited Islets 0 30 60 90 120 0 200 400 600 Time (min.) Blood Glucose (mg/dL) Allo-Evasion 5.0 Islets + PBMCs Allo-Evasion 5.0 Islets Glucose Tolerance Test
Slide 17: Data support development of CNTY-813 as an off-the-shelf cell therapy for T1D
17 These data support the development of CNTY-813 as a potentially broadly accessible off-the-shelf cell therapy for Type 1 Diabetes DIFFERENTIATION PLATFORM • Reproducible, bioreactor-enabled differentiation from GMP MCB • Phase 1 clinical manufacturing process established • CNTY-813 specs: – >95%