MuSK-CAART

Potential treatment under development for patients with myasthenia gravis (MG)

Precision Approach to Address the Underlying Cause of Disease

Our second candidate, MuSK-CAART, is designed to treat myasthenia gravis (MG), an autoimmune disease affecting the neuromuscular junction that can lead to motor impairment, muscle weakness, and respiratory failure.

Other

Therapeutic Area Indication Program Discovery Preclinical Phase 1 Phase 2/3
Neurology MuSK Myasthenia Gravis MuSK-CAART
Discovery complete
Preclinical in progress
Phase 1 not started
Phase 2/3 not started

1 In our discovery stage, we perform epitope mapping and optimize CAAR construct and design.

MuSK-CAART Strikes a Hopeful Note for Patients with MG

MuSK-CAART targets B cells that produce autoantibodies against muscle-specific kinase (MuSK), a transmembrane protein found in muscle cells that is required for the formation and maintenance of the neuromuscular junction.

About Muscle-Specific Kinase Myasthenia Gravis (MuSK MG)

MG is an autoimmune disease caused by autoantibodies targeting parts of the neuromuscular junction, leading to motor impairment, shortness of breath, disabling fatigue, and episodes of respiratory failure. Generalized MG, or gMG, affects approximately 50,000 to 80,000 patients in the United States.

gMG can be classified into two primary types:

  • AChR MG B cells produce autoantibodies against the acetylcholine receptor (AChR). Patients are typically treated with acetylcholinesterase inhibitors.
  • MuSK MG B cells produce autoantibodies against MuSK, a transmembrane protein on the surface of the muscle membrane. These patients typically do not respond to acetylcholinesterase inhibitors and are treated with corticosteroids, generalized immunosuppressants, and in cases of severe disease, intravenous immunoglobulin and rituximab. However, these methods are associated with relapse and often, ongoing dependence on corticosteroids.
  • 50,000 to 80,000 patients in the U.S. are affected by generalized MG (gMG).
  • ~6% to 7.5% of patients with gMG have autoantibodies against MuSK.
  • ~85% of patients with gMG have autoantibodies against AChR.

MuSK-CAART Showed Similar Potency Against Target Cells that Bind to Different Epitopes1

Preclinical Studies

In Vivo Studies

The activity of MuSK-CAART was evaluated in an animal model in comparison to CART19 cells, where they demonstrated specific in vivo target engagement through elimination of anti-MuSK target cells.1 Further studies to enable an IND application are currently ongoing.

1 2020 AAN Virtual Presentation, https://www.cabalettabio.com/technology/posters-publications

In Vitro Studies

MuSK-CAART has shown promising preclinical results, with in vitro demonstration of selective and specific target engagement1. Additional in vitro studies, including evaluation with a membrane protein array incorporating ~6,000 human proteins, has shown no off-target toxicity to date.

1 2020 AAN Virtual Presentation, https://www.cabalettabio.com/technology/posters-publications

Posters & Publications

Learn more about our scientific research through posters at leading conferences and publications in peer-reviewed journals.

Examine Our Findings

Presentations

Interested in the overview? These presentations hit the right notes.