Century Therapeutics (NASDAQ: IPSC) details CNTY-813 diabetes cell therapy data
Rhea-AI Filing Summary
Century Therapeutics filed an 8-K after presenting new preclinical data for CNTY-813, its iPSC-derived islet replacement therapy for type 1 diabetes, at the American Diabetes Association 2026 Scientific Sessions. CNTY-813 uses the company’s Allo-Evasion™ 5.0 immune evasion technology.
In diabetic mouse models, CNTY-813 islet cells rapidly restored normal blood sugar and maintained glucose control for more than eight months, with glucose normalization within 60 minutes on tolerance testing. Safety data showed stable graft morphology, no abnormal outgrowth, and no tumorigenesis across over 140 mice infused with one billion cells.
The company also reported strong in vitro and in vivo immune protection, including preserved C-peptide secretion and glucose tolerance in a humanized allogeneic rejection model, and consistent product quality from its Phase 1 manufacturing process. Century is targeting an IND submission for CNTY-813 in the fourth quarter of 2026 and anticipates initial clinical data in the second half of 2027.
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Insights
Preclinical CNTY-813 data strengthen the T1D pipeline story but remain early-stage.
Century Therapeutics is highlighting CNTY-813 as a potential off-the-shelf islet replacement therapy using its Allo-Evasion™ 5.0 platform. The preclinical package spans glucose control, safety, immune evasion, and manufacturing readiness, which together outline a coherent case for moving into first-in-human testing.
Functionally, CNTY-813 restored normoglycemia in streptozotocin-rendered diabetic mice for over eight months and showed glucose tolerance normalization within 60 minutes, while maintaining stable graft morphology and no tumorigenesis in more than 140 mice receiving one billion cells. Immune-evasion data in vitro and in a humanized allogeneic rejection model suggest protection from T cells, NK cells, and humoral mechanisms.
Operationally, the company reports consistent product quality from its Phase 1 manufacturing process and sets explicit timelines: an IND submission targeted for Q4 2026 and initial clinical data in the second half of 2027. Actual impact will depend on future regulatory feedback and whether clinical outcomes replicate these preclinical findings.
8-K Event Classification
Key Figures
Key Terms
iPSC-derived islet replacement therapy medical
Allo-Evasion™ 5.0 medical
streptozotocin-rendered diabetic mice medical
humanized mouse allogeneic graft rejection model medical
Investigational New Drug (IND) regulatory
GMP Master Cell Bank technical
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
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FORM
CURRENT REPORT
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| Item 8.01 | Other Events |
On June 8, 2026, Century Therapeutics, Inc. (the “Company”) issued a press release announcing that preclinical data from the Company’s iPSC-derived cell therapy platform was presented at the American Diabetes Association (ADA) 2026 Scientific Sessions (the “Conference”) being held June 5-8th in New Orleans, Louisiana. A copy of the press release is filed as Exhibit 99.1 to this Current Report on Form 8-K and is incorporated herein by reference.
A copy of the slides presented by the Company at the Conference is filed as Exhibit 99.2 to this Current Report on Form 8-K and is incorporated herein by reference. The Company undertakes no obligation to update, supplement or amend the materials attached hereto as Exhibit 99.2.
| Item 9.01 | Financial Statements and Exhibits |
(d) Exhibits
| Exhibit No. |
Document | |
| 99.1 | Press Release of Century Therapeutics, Inc., dated June 8, 2026 | |
| 99.2 | American Diabetes Association (ADA) 2026 Scientific Sessions Presentation Slides of Century Therapeutics, Inc., dated June 8, 2026 | |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document) |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| CENTURY THERAPEUTICS, INC. | ||
| By: | /s/ Brent Pfeiffenberger, Pharm.D. | |
| Name: | Brent Pfeiffenberger, Pharm.D. | |
| Title: | President, Chief Executive Officer and Chairman of the Board of Directors | |
Date: June 8, 2026
Exhibit 99.1
New CNTY-813 Preclinical Data Demonstrate Durable Glucose Control, Immune Evasion Under Alloimmune Pressure, and Scalable Manufacturing at ADA 2026
| · | Advancing CNTY-813 as a potential functional cure in Type 1 Diabetes |
| · | CNTY-813 iPSC-derived islet replacement therapy demonstrates durable in-vivo glucose control maintained for more than eight months in preclinical models |
| · | Allo-Evasion™ 5.0 maintains insulin secretion and maintained normoglycemia under allogeneic immune pressure in humanized mouse model without immunosuppression |
| · | Phase 1 clinical manufacturing process has been established demonstrating consistent endocrine purity and optimal islet cell content |
| · | CNTY-813 IND submission on track for 4Q 2026; initial clinical data expected in 2H 2027 |
PHILADELPHIA, June 8, 2026 - Century Therapeutics, Inc. (‘Century’, NASDAQ: IPSC), a biotechnology company developing induced pluripotent stem cell (iPSC)-derived cell therapies for autoimmune diseases, including type 1 diabetes (T1D), and cancer, today announced the presentation of new preclinical data from CNTY-813, Century’s iPSC-derived islet replacement therapy engineered with Allo-Evasion™ 5.0, in an oral presentation at the American Diabetes Association (ADA) 86th Scientific Sessions in New Orleans, Louisiana.
T1D affects approximately nine million people worldwide. While islet cell transplantation has demonstrated the potential to restore insulin independence, with insulin independence achieved in approximately 70% of patients receiving cadaveric islet transplantation at one year, the current approach requires chronic systemic immunosuppression. The need for chronic immunosuppression limits the utility of cell transplantation for the majority of T1D patients. CNTY-813 is designed to address this directly: a potential off-the-shelf, iPSC-derived islet replacement therapy engineered with Allo-Evasion™ 5.0 to eliminate the need for immunosuppression and exogenous insulin. Based on preclinical data to date, Century believes CNTY-813 has the potential to deliver what no prior therapy has achieved, a functional cure for T1D without the need for chronic immunosuppression.
The presentation, titled “CNTY-813: Scalable Production of Allo-Evasion™ 5.0-Engineered iPSC Beta Islets for Off-the-Shelf Cell Therapies” (Abstract 1318-OR), was delivered by Leonardo Velazco-Cruz, Ph.D., at 2:45 p.m. CT. The data highlight CNTY-813’s demonstrated functional potency, scalable manufacturing, engraftment with no evidence of abnormal outgrowth or tumorigenesis, and ability to maintain glucose control under allogeneic immune pressure, a combination of properties that Century believes distinguishes CNTY-813 as a completely novel approach to islet cell replacement.
"These preclinical data advance our case for a potentially functional cure for type 1 diabetes. Across a range of preclinical studies, CNTY-813 has now demonstrated what we believe are critical prerequisites for a potentially curative islet replacement therapy: glucose-responsive function comparable to primary islets, graft stability with no evidence of tumorigenesis, and immune evasion engineered to eliminate the need for chronic immunosuppression," said Brent Pfeiffenberger, Pharm.D., Chief Executive Officer of Century Therapeutics. "Having established our Phase 1 manufacturing process and demonstrated consistent product quality across independent batches, we are confident in our readiness for clinical trials and the potential to scale for broad patient access. With our IND submission on track for the fourth quarter of 2026 and initial clinical data anticipated in the second half of 2027, we are executing with discipline toward what we believe is a highly competitive and differentiated program.”
Preclinical data highlights
The oral presentation highlighted new preclinical data from CNTY-813 studies as outlined below. The full presentation is available on the Presentations tab of Century’s investor relations website at investors.centurytx.com/events-and-presentations.
Durable glucose control in vivo
CNTY-813 iPSC-derived islet cells rapidly restored normoglycemia in streptozotocin-rendered diabetic mice and maintained glucose control for greater than eight months following transplantation. New data demonstrate that Allo-Evasion™ 5.0-edited cells showed comparable glucose control to non-edited cells, confirming the immune evasion engineering modifications do not affect the islets’ ability to control glucose. Islet performance in a glucose tolerance test demonstrated glucose normalization within 60 minutes in both edited and unedited islets.
Cell composition and acceptable post-mitotic safety profile
New single-cell RNA sequencing analysis demonstrated that CNTY-813 contains a consistent and optimal ratio of differentiated cell types in islet clusters, with beta cells comprising greater than 50% of total cell composition. Greater than 98% of cells were identified in G1 phase, indicating cell cycle exit on par with primary islets. In vivo graft analysis at two, four, and eight weeks post-infusion confirmed endocrine graft morphology was maintained with no evidence of cyst formation or abnormal outgrowth, as assessed by Ki67 staining over time. No tumorigenesis was observed in more than 140 mice with more than three months of follow-up across one billion cells infused.
Immune evasion: in vitro protection
Additional data from multiple in vitro assays demonstrated that CNTY-813 cells containing Allo-Evasion™ 5.0 edits provided significant protection from natural killer (NK) cell clearance, induced rapid IgG cleavage of a surrogate anti-drug antibody, and demonstrated protection from antibody-mediated phagocytosis. These results confirm functional activity across all three engineered immune protection layers: T cells, NK cells, and humoral evasion.
Immune evasion: in vivo protection in humanized mouse model
New data from a humanized mouse allogeneic graft rejection model engrafted with healthy donor peripheral blood mononuclear cells (PBMCs) to support survival of functional human T cells without graft-versus-host disease and human NK cells, demonstrated that mice transplanted with CNTY-813 maintained normal C-peptide secretion function through 42 days post-transplant. In contrast, mice transplanted with unedited islet grafts showed rapid functional deterioration and allo-rejection with PBMC co-engraftment. Consistent with immune evasion, Allo-Evasion™ 5.0-engineered islets maintained glucose tolerance in a glucose tolerance test under allogeneic immune pressure while unedited islets showed reduced function.
Consistent product quality from Phase 1 clinical manufacturing process
Century has established its manufacturing processes for Phase 1 clinical trial supply. New data demonstrated consistent product quality across three separate at-scale experiments from Century’s GMP Master Cell Bank, comprising 11 samples, with optimal endocrine purity, islet cell content, and minimal islet cell impurities across all samples. The 29-day, bioreactor-based suspension differentiation process met pre-defined purity specifications at each stage. The process supports cryopreservation with retained post-thaw potency.
Upcoming CNTY-813 milestones
| · | IND submission (4Q 2026): Century expects to submit an Investigational New Drug application for CNTY-813 in the fourth quarter of 2026, subject to completion of remaining IND-enabling studies. |
| · | Initial clinical data (2H 2027): Initial safety and early efficacy data from the first-in-human CNTY-813 study are anticipated in the second half of 2027. |
About CNTY-813
CNTY-813 is Century’s potential iPSC-derived islet replacement therapy for T1D. CNTY-813 is engineered with Allo-Evasion™ 5.0, Century’s proprietary immune evasion technology, which is designed to enable durable engraftment without chronic systemic immunosuppression, the central unresolved limitation of every currently approved or late-stage cell therapy approach to T1D. Preclinical data demonstrated robust glucose-responsive function, favorable pre-clinical safety profile, scalable and reproducible manufacturing, and immune protection under alloimmune pressure. Century is targeting an IND submission for CNTY-813 in the fourth quarter of 2026.
About Century Therapeutics
Century Therapeutics (NASDAQ: IPSC) is a biotechnology company advancing a pipeline of induced pluripotent stem cell (iPSC)-derived cell therapies with the potential to meaningfully address autoimmune diseases, including type 1 diabetes, and cancer. Century’s therapies are derived from its iPSC cell foundry and leverage its novel immune evasion engineering technology, Allo-Evasion™. Century believes its approach to developing off-the-shelf cell therapies will expand patient access and provide advantages over existing cell therapies which will ultimately advance the course of care. For more information on Century Therapeutics, please visit www.centurytx.com and connect with us on LinkedIn.
Forward-looking statements
This press release 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 press release, other than statements of historical facts or statements that relate to present facts or current conditions, including but not limited to, statements about our timing and expectations regarding our preclinical and clinical development programs, including planned development of CNTY-813, therapeutic potential and market opportunity, ongoing and planned regulatory submissions and interactions, the achievement of developmental milestones, corporate strategies, and anticipated data readouts, are forward-looking statements. These statements involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance, or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. In some cases, you can identify forward-looking statements by terms such as “may,” “might,” “will,” “should,” “expect,” “plan,” “aim,” “seek,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “forecast,” “potential” or “continue” or the negative of these terms or other similar expressions. The forward-looking statements in this press release are only predictions. We have based these forward-looking statements largely on our current expectations and projections about future events and financial trends that we believe may affect our business, financial condition, and results of operations. These forward-looking statements speak only as of the date of this press release and are subject to a number of risks, uncertainties and assumptions, some of which cannot be predicted or quantified and some of which are beyond our control, including, among others: our ability to successfully advance our current and future product candidates through development activities, preclinical studies, and clinical trials; our ability to meet development milestones on anticipated timelines; uncertainties inherent in the results of preliminary data, and pre-clinical studies , which may not be predictive of final results or the results of clinical trials; our ability to obtain clearance of our future IND or CTA submissions and commence and complete clinical trials on expected timelines, or at all; our reliance on the maintenance of certain key collaborative relationships for the manufacturing and development of our product candidates; the timing, scope and likelihood of regulatory filings and approvals, including final regulatory approval of our product candidates; the impact of geopolitical issues, trade disputes and tariffs, banking instability and inflation on our business and operations, supply chain and labor force; the performance of third parties in connection with the development of our product candidates, including third parties conducting our clinical trials as well as third-party suppliers and manufacturers; our ability to successfully commercialize our product candidates and develop sales and marketing capabilities, if our product candidates are approved; our ability to recruit and maintain key members of management and our ability to maintain and successfully enforce adequate intellectual property protection. These and other risks and uncertainties are described more fully in the “Risk Factors” section of our most recent filings with the Securities and Exchange Commission and available at www.sec.gov. You should not rely on these forward-looking statements as predictions of future events. The events and circumstances reflected in our forward-looking statements may not be achieved or occur, and actual results could differ materially from those projected in the forward-looking statements. Moreover, we operate in a dynamic industry and economy. New risk factors and uncertainties may emerge from time to time, and it is not possible for management to predict all risk factors and uncertainties that we may face. Except as required by applicable law, we do not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise.
For more information:
Century Therapeutics
Douglas Carr
Senior Vice President, Finance
LifeSci Advisors, LLC
Corey Davis, Ph.D.
212-915-2577
Exhibit 99.2
| CNTY-813: Scalable Production of Allo-Evasion 5.0- Engineered iPSC Islets for Off-the-Shelf Cell Therapies Leonardo Velazco-Cruz, PhD |
| 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 therapy for T1D – The content is intended for scientific and educational discussion – No clinical recommendations will be made Disclosures |
| 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 or statements that relate to present facts or current conditions, including but not limited to, statements regarding our clinical development plans and timelines and the initial safety and efficacy profiles of CNTY-813 and statements regarding our preclinical development programs, including initial preclinical data and development plans and timelines are forward-looking statements. These statements involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance, or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. In some cases, you can identify forward-looking statements by terms such as “may,” “might,” “will,” “should,” “expect,” “plan,” “aim,” “seek,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “forecast,” “potential” or “continue” or the negative of these terms or other similar expressions. The forward-looking statements in this presentation are only predictions. We have based these forward-looking statements largely on our current expectations and projections about future events and financial trends that we believe may affect our business, financial condition, and results of operations. These forward-looking statements speak only as of the date of this presentation and are subject to a number of risks, uncertainties and assumptions, some of which cannot be predicted or quantified and some of which are beyond our control, including, among others: our ability to successfully advance our current and future product candidates through development activities, preclinical studies, and clinical trials; our ability to progress CNTY-813 through clinical development; our ability to meet development milestones on anticipated timelines; uncertainties inherent in the results of preliminary data, pre-clinical studies and earlier-stage clinical trials, which may not be predictive of final results or the results of later-stage clinical trials; our ability to obtain clearance of our future IND or CTA submissions and commence and complete clinical trials on expected timelines, or at all; our reliance on the maintenance of certain key collaborative relationships for the manufacturing and development of our product candidates; the timing, scope and likelihood of regulatory filings and approvals, including final regulatory approval of our product candidates; the impact of geopolitical issues, trade disputes and tariffs, banking instability and inflation on our business and operations, supply chain and labor force; the performance of third parties in connection with the development of our product candidates, including third parties conducting our clinical trials as well as third-party suppliers and manufacturers; our ability to successfully commercialize our product candidates and develop sales and marketing capabilities, if our product candidates are approved; our ability to recruit and maintain key members of management and our ability to maintain and successfully enforce adequate intellectual property protection. These and other risks and uncertainties are described more fully in the “Risk Factors” section of our most recent filings with the Securities and Exchange Commission and available at www.sec.gov. You should not rely on these forward-looking statements as predictions of future events. The events and circumstances reflected in our forward-looking statements may not be achieved or occur, and actual results could differ materially from those projected in the forward-looking statements. Moreover, we operate in a dynamic industry and economy. New risk factors and uncertainties may emerge from time to time, and it is not possible for management to predict all risk factors and uncertainties that we may face. Except as required by applicable law, we do not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. |
| 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://www.citregistry.org/system/files/CITR%2012th%20Allograft%20Report_2025_Final.pdf Islet transplantation provides a potentially curative therapy for T1D Insulin independence achieved for one year in ~70% of patients receiving allogenic cadaveric islet transplantation1 Source: Marfil-Garza et al. 2022; Pancreatic islet transplantation in type 1 diabetes: 20-year experience from a single-centre cohort in Canada Supply and chronic immunosuppression limit the broader use of T1D cell therapies CNTY-813: Century’s islets with Allo-Evasion 5.0 are designed to address key challenges in T1D cell therapy |
| 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 key capabilities for off-the-shelf T1D cell therapy FUNCTIONAL ISLETS • Glucose-responsive insulin secretion • In vivo glucose control in diabetic mice • No safety events observed to date in preclinical models – i.e., cyst or tumor formation ALLO-EVASION 5.0 • T cell protection • NK cell protection • Reduced humoral immune clearance |
| 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 II Endocrine β Cell Stage 1 Stage 2 Stage 3 Stage 4 Stage 5 Stage 6 Consistent Differentiation • Surpassed the necessary purity at every stage • >95% Endocrine • 50-60% Beta Cells (Insulin Producing) Stage 1: Definitive Endoderm Stage 4: Pancreatic Progenitor II Stage 6: Islet Endocrine Stage 6: Beta Cell Mean (n) 97.3 (20) 98.2 (24) 95.9 (32) 60.2 (32) |
| 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-Thaw Maturation → Final Fresh Product Consistent final product flow cytometry profiles across 3 at-scale batches Source: Company data on file |
| 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 Islets 0 10000 20000 30000 40000 u UI Insulin/ 1E6 Cells 2mM Glucose 20mM Glucose Source: Company data on file ∆GSIS |
| 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 area = normal blood glucose range 0 25 50 75 10 125 150 175 20 2 5 250 275 30 0 100 200 300 400 500 600 Days Post Treatment Blood Glucose m( g/dL) No Treatment Normoglycemia Control CNTY-813 (SRC) (5M) Unedited CNTY Islet Cells (5M) 0 20 40 60 80 100 120 0 100 200 300 400 500 600 Time (min) Blood Glucose (mg/dL) Diabetic Control Unedited CNTY Islet Cells (5M) CNTY-813 (SRC) (5M) Glucose Control Glucose Control Glucose Tolerance Test Source: Company data on file Mean +/- SEM Mean +/- SD |
| 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; ⍺-cell: GCG,ARX; δ-cell: SST; Exocrine/Ductal: KRT19; FEV+ Islet Cell: FEV+SLC18A1+ scRNAseq Cell Cycle Annotations Diff. Stage: iPSC 1 2 3 4 5 6 scRNAseq Cell Type Annotations • CNTY-813 achieves a defined islet endocrine composition, with beta cells as the predominant population • Data is consistent with cell cycle exit on par with primary islets by end of manufacture (>98% G1 phase identity) |
| 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 formation was observed through 8 weeks ✓ No tumorigenesis observed in >140 mice with >3-month follow up (>1B cells infused) Quantification of Ki67+ over time Ki67 staining includes host-derived cells; not human specific. INS: Insulin stain; CHGA: CHGA stain; Ki67: Stain for Ki67; DAPI: nuclear stain 200µm Source: Company data on file |
| 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.com/wp-content/uploads/ASH_Welstead_Universal-Protection-of-Allogenic-T-Cells-Final.pdf 2. https://ashpublications.org/bloodadvances/article/doi/10.1182/bloodadvances.2024013436/518079/Universal-Protection-of-Allogeneic-T-Cell 3. Peraro et al, Mol. Therapy 2021, 29(12), 3398-3409; https://pmc.ncbi.nlm.nih.gov/articles/PMC8636170 b2M KO (HLA-I) CIITA KO (HLA-II) CD8+ T Cell CD4+ T Cell Pan NK Inhibitory ligand Fc NK cell No HLA-I Prevents recognition by CD8+ cells T cells No HLA-II Prevents recognition by CD4+ cells T cells IgG Cleavage Reduces Fc binding and humoral activity CD300a TASR Ligand Inhibits NK cell activation ALLO-EVASION 5.0 |
| 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 IgG after 1 hour in cleavage assay CNTY-813 did not activate or get cleared by NK cells CNTY-813 degraded IgG antibodies in vitro CNTY-813 protection from Ab-mediated phagocytosis Protection from ADCP achieved against an antibody targeting EpCAM 0.25:1 0.5:1 1:1 2:1 10 20 30 40 E:T ratio CD107a+ (%) WT DKO CTNY-813 **** **** **** **** NK Activation Source: Company data on file *, p<0.05; **, p<0.01; ***, p<0.001; ****, p<0.0001 Donor 1 Donor 2 0 25 50 75 100 125 NK Cell Donor Percent Survival (%) DKO CNTY-813 ✱✱✱ ✱✱✱ |
| 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-rejection mediated by human T cells and NK cells (huPBMCs) NSG-MHC I/II DKO+/+ NSG-Tg(Hu-IL15)+/+ X No GvHD Human NK cell support Human immune-cell engraftment supports functional testing of allo-rejection in vivo |
| 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 Unedited Islets 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) CNTY-813 Allo-Evasion 5.0 Islets + PBMCs CNTY-813 Allo-Evasion 5.0 Islets Glucose Stimulation Index Mean ± SEM Allo-Rejection Reduced function with PBMC engraftment Maintained function with PBMC engraftment Unedited Islets Allo-Evasion 5.0 Islets Readout Human C-peptide stimulation index (over-baseline) Interpretation Higher response indicates preserved graft insulin secretion C-Peptide is a surrogate for insulin Source: Company data on file |
| 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 (GTT) Unedited Islets Allo-Evasion 5.0 Islets (11 weeks post-islet infusion) Mean ± SD Readout Human blood glucose as depicted by area under the curve (AUC) during glucose tolerance test Interpretation Lower AUC indicates faster glucose clearance and better glucose control Allo-Evasion 5.0 protected CNTY-813 from rejection in a humanized mouse Reduced function with PBMC engraftment Maintained function with PBMC engraftment Source: Company data on file |
| 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% islet endocrine – >50% beta cell identity CNTY-813 demonstrated reproducible differentiation, durable glucose control, and immune-evasive function in preclinical models FUNCTIONAL ISLETS • GSIS potency similar to primary islets • Rapid and durable glucose control observed in diabetic mice • Maintained graft identity with a favorable safety profile ALLO-EVASION 5.0 • Engineered to reduce T-cell, NK-cell, and humoral immune recognition • Protection from NK and humoral clearance demonstrated • Preserved graft function under alloimmune pressure in vivo |
