Century Therapeutics announced two poster presentations at the ASGCT 27th Annual Meeting. The data presented highlights the potential of the Company?s lead candidate, CNTY-101, to treat B-cell driven autoimmune diseases including SLE. Additionally, the Company presented data which further demonstrates the capabilities of its Allo-Evasion?

technology through new preclinical data of a CD300a agonist which can potentially inhibit natural killer (NK) cell alloreactivity. Characterization of CNTY-101, an Allogeneic Anti-CD19 iPSC-Derived NK Product, for the Treatment of B Cell-Driven Autoimmune Diseases, Poster Board Number: 1815, session Title: Immune Targeting and Approaches with Genetically-Modified Cells and Cell TherapiesSession Date & Time: May 10th, 2024, at,:00 PM -7:00 PM ET. B-cell targeted allogeneic iPSC-derived immune effector cells have the potential to deliver long-term remission in autoimmune diseases mediated by pathogenic B-cells, including SLE.

Century?s lead candidate, CNTY-101, is currently being evaluated in patients with B-cell Non-Hodgkin Lymphoma, and studies in SLE patients will soon begin. Early clinical experience with this iPSC-derived NK cell demonstrates the potential for tight control over drug exposure, potentially enabling B-cell depletion without causing prolonged B-cell aplasia. CNTY-101 was engineered with multiple precision gene edits, incorporating a CD19-specific CAR, homeostatic cytokine support for enhanced persistence, Allo-Evasion?

edits to prevent rejection by the patients? immune system, and a safety switch. In non-clinical studies the Company demonstrated that CNTY-101 was more potent in vitro than peripheral blood mononuclear cell (PBMC) derived CAR-T cells in inducing CD19-specific cytolysis of B-cells isolated from multiple healthy and SLE patient donors with less detectable inflammatory cytokine secretion after B-cell depletion.Beyond HLA-E: Universal Protection of Allogeneic T Cells from, Natural Killer Cells Via CD300a Agonism, Poster Board Number: 1816, Session Title: Immune Targeting and Approaches with Genetically-Modified Cells and Cell Therapies, Session Date & Time: May 10th, 2024, at 12:00 PM -7:00 PM ET.

The therapeutic potential of allogeneic, off-the-shelf T cell therapies is hindered by immune-mediated rejection by the host. While ablation of human leukocyte antigen (HLA) removes most T cell and humoral alloreactivity, this renders the cells vulnerable to attack by natural killer (NK) cells. Expression of natural inhibitory ligands such as HLA-E can diminish NK mediated killing, however, the extent of this resistance varies from host to host and a solution that allows for universal protection again NK cell response has not been found.

To overcome this challenge, Century is engineering a class of synthetic ligands called trans antigen signaling receptors (TASRs), which agonize CD300a, an inhibitory receptor present on the vast majority of NK cells across a broad sampling of the population. Researchers assessed expression of a CD300a TASR on T cells edited to lack HLA-I in a large human cohort study. CD300a TASR outperformed leading alternatives, including CD47 and HLA-E, both in terms of protection against NK mediated killing as well as enhanced CAR-T cell efficacy under allogeneic pressure.

Notably, peripheral blood from CMV-seropositive donors (>50% of the population) expressed NK cell subsets with relative resistance to HLA-E mediated inhibition, while cells expressing CD300a TASR were protected, broadening the population with the potential to be effectively treated by next-generation allogeneic cell therapies. As such, surface expression of an engineered CD300a agonist acted as a universal ligand against NK cell alloreactivity. CD300a TASR has the potential to be a solution to a key constraint against the broad use of allogeneic cell therapies for hematologic malignancies, cancer, autoimmunity and beyond.

These results further strengthen Century?s Allo-Evasion? platform, focused on designing cells capable of evading identification and destruction by the host immune system while simultaneously allowing for repeat dosing of CAR-modified cell therapies to generate durable responses across autoimmune and inflammatory diseases as well as hematologic and solid tumors.