AbbVie’s Strategic Leap into In Vivo CAR-T with $2.1 Billion Capstan Acquisition to Transform Autoimmune Disease Treatment

AbbVie is making a significant move into the in vivo CAR-T market by acquiring Capstan Therapeutics for up to $2.1 billion in cash. This acquisition brings Capstan’s lead candidate, CPTX2309, a phase 1 in vivo anti-CD19 CAR-T therapy for autoimmune diseases, into AbbVie’s pipeline.

Here’s a breakdown of the key aspects:

CPTX2309 and In Vivo CAR-T Technology:

• Mechanism: CPTX2309 utilizes an anti-CD19 CAR mRNA payload encapsulated within a lipid nanoparticle (LNP). This LNP has a targeting antibody that enables specific delivery of the mRNA to CD8-positive T cells inside the body. Once delivered, the mRNA reprograms these T cells to become functional CAR-T cells.
• Advantages of In Vivo CAR-T: This approach aims to overcome several limitations of traditional ex vivo CAR-T therapies:

  • Eliminates Ex Vivo Manufacturing: Traditional CAR-T requires extracting a patient’s T cells, genetically modifying them outside the body in a specialized facility, and then reinfusing them. In vivo CAR-T eliminates this complex, time-consuming, and expensive manufacturing process.
  • No Lymphodepleting Chemotherapy: Conventional CAR-T often necessitates lymphodepleting chemotherapy before infusion to make space for the new CAR-T cells. In vivo CAR-T potentially removes the need for this harsh preconditioning.
  • Scalability and Accessibility: By simplifying the process, in vivo CAR-T could make these powerful therapies more scalable, accessible, and potentially more affordable for a wider patient population.
  • Off-the-Shelf: CPTX2309 is designed to be an “off-the-shelf” product, meaning it can be administered directly to patients without a lengthy vein-to-vein waiting period.
  • Transient Expression: The mRNA-based approach leads to transient CAR expression, which may offer a more tunable and potentially safer profile compared to permanent genetic modifications.

• Current Status: CPTX2309 is currently in a Phase 1 study in healthy volunteers in Australia, aiming to determine a pharmacologically active dose for future phase 2 studies in autoimmune disease patients.

AbbVie’s Strategic Rationale:

• Autoimmune Disease Focus: AbbVie has a strong presence in the autoimmune market, with successful drugs like Skyrizi and Rinvoq succeeding Humira. This acquisition further solidifies their commitment to this therapeutic area by exploring a potentially curative approach.
• Immune System Reset: The goal of CPTX2309 is to achieve an “immune reset” by rapidly and profoundly depleting pathogenic B cells, followed by the repopulation of healthy, naive B cells. This aims to address the root cause of autoimmune diseases rather than just managing symptoms.
• Pipeline Expansion: Beyond CPTX2309, the acquisition includes Capstan’s preclinical programs, such as a BCMA program (with applications in oncology and autoimmune disease) and a fibroblast target for fibrotic disorders, demonstrating potential for broader therapeutic applications of the platform.

Competitive Landscape:

• While other in vivo CAR-T biotechs like Interius BioTherapeutics and Umoja Biopharma have also entered clinical trials, they are primarily targeting cancers and use lentiviral vectors. Capstan’s use of mRNA and its initial focus on autoimmune diseases differentiate its approach.

This acquisition highlights a growing trend in the pharmaceutical industry to develop more accessible and less burdensome cell therapies for a wider range of diseases.