Capstan Therapeutics has achieved a significant milestone in autoimmune disease treatment by successfully dosing the first participants in its Phase 1 trial of CPTX2309, a groundbreaking in vivo CAR-T therapy. The San Diego-based clinical-stage biotechnology company announced that its lead anti-CD19 CAR-T candidate represents a novel approach to treating B cell-mediated autoimmune disorders without the complexities of traditional CAR-T manufacturing.
Revolutionary mRNA-Based Approach
CPTX2309 utilizes targeted lipid nanoparticles (tLNP) to deliver anti-CD19 CAR mRNA preferentially to CD8-expressing cytotoxic T cells directly within the patient's body. This mRNA-based approach is designed to achieve rapid, deep, and transient B cell depletion without requiring chemotherapy, cell manipulation, viral vectors, or DNA integration into the genome.
"With CPTX2309, our therapeutic goal is to achieve immune reset through rapid and profound B cell depletion using a transient, tunable, and fully off-the-shelf in vivo CAR-T technology," said Ramin Farzaneh-Far, M.D., Chief Medical Officer at Capstan.
Clinical Trial Design and Objectives
The Phase 1 trial will assess the safety, tolerability, pharmacokinetics, and pharmacodynamic activity of CPTX2309 treatment in healthy volunteers at various dose levels. The study specifically focuses on peripheral B cell depletion and recovery patterns following treatment administration.
Dr. Farzaneh-Far emphasized the strategic advantages of testing in healthy volunteers: "The focus on a Phase 1 healthy volunteer population allows us to dose escalate efficiently, and importantly, underscores the potential safety advantages of an approach that does not involve lymphodepletion or permanent CAR integration into the genome."
Promising Preclinical Results
Preclinical studies provided strong support for the clinical evaluation of CPTX2309. The therapy demonstrated rapid, deep, and transient B cell depletion in both blood and tissues, which supported the clinical evaluation at the planned dose levels and regimens. Notably, preclinical data showed that CPTX2309 demonstrates robust in vivo engineering of CD8+ CAR T cells, profound B cell depletion in blood and tissues, and repopulation with predominantly naïve B cells in non-human primates.
CellSeeker Platform Technology
The therapy is built on Capstan's proprietary CellSeeker™ tLNP platform technology, which consists of novel lipid nanoparticles conjugated with recombinant protein binders, such as monoclonal antibodies. This platform delivers RNA payloads capable of reprogramming cells in vivo, combining the potency of CAR-T therapy with the convenience of an off-the-shelf product.
Path Forward
The objective of this Phase 1 trial is to determine a pharmacologically active dose or doses that can be advanced into Phase 2 studies to treat patients with autoimmune disease. CPTX2309 is designed to target B cell-mediated autoimmune disorders through tunable and dose-dependent levels of CAR expression with a potentially favorable clinical safety profile.
The trial is currently being conducted in Australia, marking Capstan's entry into clinical development as the company focuses on developing in vivo CAR-T therapies for autoimmune diseases. This approach represents a significant departure from traditional CAR-T manufacturing, potentially offering patients a more accessible and safer treatment option for B cell-mediated autoimmune conditions.
