Our clinical trials with CABA-201 (investigational CD19-CAR T cell therapy) in lupus and myositis are now recruiting.

CABA-201

Treatment with potential to “reset the immune system" for patients with severe autoimmune diseases

Expanding Our Impact in Autoimmune Disease

CABA-201 is a fully human CD19 chimeric antigen receptor (CAR) T cell therapy containing a 4-1BB co-stimulatory domain. Cabaletta is advancing Phase 1/2 clinical trials in systemic lupus erythematous, myositis, systemic sclerosis and generalized myasthenia gravis, with potential application in a broad range of other autoimmune diseases.

CARTA CABA-201 C himeric A ntigen R eceptor T cells for A utoimmunity 4-1BB CD19-CAR T CABA™ PlatformProgramIndicationIND clearedIND clearedIND clearedMyositis(IIM, IdiopathicInflammatory Myopathy)1Systemic LupusErythematosus (SLE)1 Multiple UndisclosedIndicationsSystemic Sclerosis(SSc)1Generalized MyastheniaGravis (gMG)1DiscoveryDermatomyositisAnti-Synthetase SyndromeLupus NephritisNon-Renal SLEAChR Antibody-PositiveAChR Antibody-NegativeSevere Skin InvolvementSevere Organ InvolvementImmune-Mediated Necrotizing MyopathyPreclinicalPhase 1/2Phase 2/3

1CABA-201 is being evaluated in separate clinical trials for myositis, SLE, SSc & gMG.

Potential of CD19-CAR T Cell Therapy

Over the past couple of years, academic groups have published findings demonstrating the potential of CD19-CAR T to transform the course of autoimmune disease. Emerging data in patients with systemic lupus erythematosus, myositis and systemic sclerosis suggests the potential of a one-time treatment with a 4-1BB-containing CD19-CAR T cell therapy, with a high degree of similarity to CABA-201, to achieve robust improvement in clinical disease activity within 3 months of treatment, with a generally favorable safety profile.

Our licensed fully human CD19 binder has been clinically evaluated in a dual-CD19xCD22 CAR T in cancer through an investigator-initiated trial, where it has shown promising tolerability in ~20 patients. Based on the similarity between CABA-201 and the CD19-CAR T construct employed in the academic reports, including incorporation of a 4-1BB co-stimulatory domain, CABA-201 may have the potential to transform the treatment of autoimmune diseases.

About SLE

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, most common in young women between the ages of 15 and 40, with higher frequency and greater severity in people of color. In SLE, the immune system attacks healthy tissue throughout the body. It is results in a range of clinical manifestations, including end organ damage and an increased risk of death. SLE affects up to 320,000 patients in the U.S. Lupus nephritis (LN) is the most common end-organ manifestation of SLE, affecting approximately 40% of SLE patients. Among these patients, the risk of end-stage renal disease is approximately 17% and the risk of death is approximately 12%, each within 10 years of diagnosis.

About Myositis

Myositis refers to a group of autoimmune diseases characterized by severe inflammation and muscle weakness. It commonly impacts women of middle age, and in some cases, myositis may also affect other organs and systems in the body, such as the lungs, heart, or skin. Myositis is classified into several subtypes based on the underlying immune mechanisms and clinical characteristics. Although the pathogenesis of myositis is not well understood, there are several subtypes thought to be driven by B cells, including dermatomyositis (DM), anti-synthetase syndrome (ASyS) and immune-mediated necrotizing myopathy (IMNM). All three subtypes can lead to severe functional impairment and may be life-threatening. Nearly 66,000 patients are affected by these three subtypes in the U.S.. Current standard of care typically involves medications to suppress the immune system and/or chronic intensive therapies such as intravenous immunoglobulin, or IVIg. Despite these therapies, many myositis patients have disease that remains refractory to existing medications.

About Systemic Sclerosis

Systemic Sclerosis (SSc) is rare and potentially fatal chronic autoimmune disease characterized by progressive fibrosis and scarring of the skin and internal organs that can lead to life-threatening conditions, including interstitial lung disease, pulmonary hypertension, and scleroderma renal crisis. Although the etiology of SSc is not well understood, the pathogenic role of autoantibodies and B cells in SSc provides a rationale for studying CAR T therapy in this population. Approximately 88,000 patients in the United States are affected by SSc, commonly middle-aged women. Current treatments, which have modest effects, include generalized immunosuppression or drugs targeted to specific symptomatic manifestations. In some cases, autologous hematopoietic stem cell transplant may provide some benefits in organ involvement but is associated with significant risks, including mortality, infertility, and secondary autoimmune disease, limiting its potential to be applied broadly. The risk of mortality in SSc remains high due to the lack of adequate treatments, with an average survival of approximately 12 years following initial diagnosis.

About gMG

Myasthenia gravis (MG) is a rare autoimmune disease characterized by autoantibodies that interfere with signaling at the neuromuscular junction (NMJ), leading to potentially life-threatening muscle weakness. The majority of patients with MG have autoantibodies known to be pathogenic based on their interference with proteins in the NMJ, of which the majority target AChR. Generalized MG (gMG) affects approximately 85% of the between 50,000 and 80,000 estimated MG patients in the United States. Symptoms of gMG include profound muscle weakness throughout the body, disabling fatigue, shortness of breath due to respiratory muscle weakness and risk for episodes of respiratory failure. Standard of care therapies include cholinesterase inhibitors, steroids, immunomodulators, and biologics, which often provide modest clinical effect and require chronic administration, increasing the risk of serious long-term side effects.

Clinical Trials with CABA-201

Advancing Four Phase 1/2 Studies in Autoimmune Disease

We are advancing four Phase 1/2 studies to evaluate CABA-201 in patients with systemic lupus erythematous, myositis, systemic sclerosis, and generalized myasthenia gravis. Initial clinical data with CABA-201 in the myositis and/or lupus trials is anticipated in the first half of 2024.