Introduction and Objective: Type 1 diabetes cell therapies aim to restore normoglycemia by replacing lost beta cells, but low clinical supply and the need for chronic immune suppression are key challenges. CNTY-813 overcomes these challenges via clinical-scale production of Allo-Evasion™ 5.0-engineered iPSC-derived beta islets that are engineered for immune evasion. Thus, CNTY-813 provides an off-the-shelf, functionally curative therapy for T1D without the need for chronic immune suppression. Methods: Allo 5.0 iPSCs were engineered to lack HLA class I/II and express CD300a TASR and an IgG-degrading protease and differentiated into beta islets in bioreactors (0.1-3L). Purity and potency were assessed by flow cytometry, immunohistochemistry, scRNA-seq, glucose-stimulated insulin secretion (GSIS), and streptozotocin (STZ)-diabetic mouse models. Immune protection was assessed using established in vitro and in vivo alloreactive assays. Results: Century’s 3D differentiation process yielded iPSC-derived beta islets with high purity (97.6 ± 1.5% CHGA+ endocrine cells, 61.0 ± 8.4% INS+NKX6.1+ beta cells). scRNA-seq confirmed 97% endocrine commitment, 60% beta identity, and 99% G1-arrested. Cell yields can support a ph1 clinical trial without compromising cell purity and function. In STZ-diabetic mice, Allo 5.0 islets restored normoglycemia in ≤10 days and have persisted 4 months to date; GSIS stimulation index 3 and GTT normalized glucose in 60 min. In vitro NK cytotoxicity assays showed ~100% survival at 1:1 NK:beta ratio and IDP protection was confirmed in an IgG cleavage assay. Allo 5.0 islets resisted in vivo rejection under immune pressure in an alloreactive mouse model while maintaining persistent human C-peptide secretion. Conclusion: Clinical-scale production of CNTY-813 generates high-purity iPSC-derived beta islets with robust endocrine function and the demonstrated ability to evade the host immune system. Preclinical data supports its potential as an off-the-shelf allogeneic functionally curative therapy for T1D. Disclosure L. Velazco-Cruz: Employee; Current; Century Therapeutics. J.R. Kurtz: Employee; Current; Century Therapeutics. R.M. Hasselkus: Employee; Current; Century Therapeutics. K. Atkinson: Employee; Current; Century Therapeutics. M. Brennan: Employee; Current; Century Therapeutics. D.L. Bauer: Employee; Current; Century Therapeutics. J. Regan: Employee; Current; Century Therapeutics. K. Farag: Employee; Current; Century Theraputics. N. Alexander: Employee; Current; Century Therapeutics. A.M. Perez: None. A. Cerny: None. J. Kady: None. K. Bullaughey: Employee; Current; Century Therapeutics. C. Farias Amorim: Employee; Current; Century Therapeutics. M. Brehm: None. D. Whitney: Employee; Current; Century Therapeutics, LLC. C. Cowan: Employee; Current; Century Therapeutics. G. Welstead: Employee; Current; Century Therapeutics.
Velazco-Cruz et al. (Mon,) studied this question.