CPTX-2309: An In Vivo Engineered CAR-T Cell Therapy for Autoimmune Diseases

1. Executive Summary

CPTX-2309 is an investigational therapeutic agent being developed by Capstan Therapeutics, representing a novel approach to Chimeric Antigen Receptor T-cell (CAR-T) therapy. Unlike conventional CAR-T therapies that require ex vivo manipulation of a patient's T-cells, CPTX-2309 is designed to engineer CAR-T cells directly in vivo. This is achieved using Capstan's proprietary CellSeeker™ targeted lipid nanoparticle (tLNP) technology, which delivers a messenger RNA (mRNA) payload encoding an anti-CD19 CAR specifically to CD8-expressing T-cells.[1]

Preclinical studies, primarily in non-human primates (NHPs), have demonstrated that CPTX-2309 can lead to robust engineering of CD8+ CAR T-cells, resulting in rapid and profound depletion of B-cells in both blood and tissues.[1] Importantly, this B-cell depletion is followed by repopulation with predominantly naïve B-cells, suggesting the potential for an "immune reset" without the need for lymphodepleting chemotherapy, a common and often harsh prerequisite for ex vivo CAR-T treatments.[1] The transient nature of mRNA-driven CAR expression is anticipated to offer an improved safety profile compared to viral vector-based CAR-T therapies.[2]