Century Therapeutics Showcases iPSC Platform Advances at 2024 ASGCT Meeting

Century Therapeutics, a biotechnology company specializing in induced pluripotent stem cell (iPSC)-derived therapies, has unveiled promising data at the ASGCT 27th Annual Meeting. The data presented underscores the potential of Century's lead candidate, CNTY-101, to address B-cell driven autoimmune diseases, including systemic lupus erythematosus (SLE), as well as the promise of their Allo-Evasion™ technology in enhancing allogeneic cell therapies by mitigating natural killer (NK) cell mediated rejection.

In vitro studies of CNTY-101 reveal its ability to induce CD19-specific cytolysis of B-cells, highlighting its potential to treat B-cell driven autoimmune diseases. The product, an allogeneic iPSC-derived NK cell therapy, is engineered with multiple precision gene edits. These include a CD19-specific chimeric antigen receptor (CAR), homeostatic cytokine support for enhanced persistence, and Allo-Evasion™ edits to prevent rejection by the patient’s immune system. Preclinical data indicates that CNTY-101 is more effective than peripheral blood mononuclear cell (PBMC) derived CAR-T cells in inducing CD19-specific cytolysis of B-cells, with less inflammatory cytokine secretion post B-cell depletion.

Additionally, Century Therapeutics introduced preclinical data on a novel synthetic ligand targeting CD300a, a potent inhibitory receptor present on nearly all NK cells. This synthetic ligand showcases the potential to inhibit NK cell alloreactivity, thus protecting engineered cells from NK cell mediated rejection. This approach aims to offer greater protection for a variety of allogeneic cell therapies under development.

The significance of these findings lies in Century’s continued dedication to refining their Allo-Evasion™ platform, which aims to enhance the control, durability, and tolerability of iPSC candidates compared to other cell therapies currently in development for autoimmune diseases. According to Hy Levitsky, M.D., President of Research and Development at Century Therapeutics, the data support the efficacy of CNTY-101 in eliminating CD19+ B-cells in vitro, while enhancing persistence and durability with reduced inflammatory cytokine secretion after target killing.

Century’s Allo-Evasion™ technology aims to engineer cell therapy products that can evade identification by the host immune system, enabling multiple doses without rejection. This technology incorporates three gene edits designed to avoid recognition by patient/host CD8+ T cells, CD4+ T cells, and NK cells. This is achieved through knockout of β2m to prevent CD8+ T cell recognition, knockout of CIITA to prevent CD4+ T cell recognition, and knock-in of the HLA-E gene to prevent NK cell-mediated killing.

The company’s lead candidate, CNTY-101, is currently being evaluated in patients with B-cell Non-Hodgkin Lymphoma, with upcoming studies in SLE patients. Early clinical experience suggests the potential for tight control over drug exposure, allowing B-cell depletion without causing prolonged B-cell aplasia.

Century’s innovative approach extends to the development of trans antigen signaling receptors (TASRs) which agonize CD300a, providing a universal ligand against NK cell alloreactivity. Preclinical assessments demonstrated that CD300a TASR outperformed alternatives like CD47 and HLA-E in protecting against NK-mediated killing and enhancing CAR-T cell efficacy under allogeneic pressure. This broadens the population that could benefit from next-generation allogeneic cell therapies.

In summary, Century Therapeutics' advancements in iPSC-derived cell therapies and Allo-Evasion™ technology hold significant promise for treating autoimmune diseases and enhancing the durability and efficacy of allogeneic cell therapies. These developments could lead to improved patient outcomes across a range of indications, including hematologic malignancies, cancer, and autoimmune diseases.