FDA Clears Cabaletta Bio’s CAR-T Agent CABA-201 for Trial in Myositis


This is the second IND clearance for CABA-201, which previously received clearance for evaluation in systemic lupus erythematosus, and now for active idiopathic inflammatory myopathy—also known as myositis.

Cabaletta Bio’s CABA-201, an investigational CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy intended to treat autoimmune diseases, has received clearance of its investigational new drug application by the FDA for a clinical trial in patients with active idiopathic inflammatory myopathy (IIM), also referred to as myositis.1

CABA-201 contains a 4-1BB costimulatory domain and is intended to deplete B-cells in order to “reset” the immune systems of patients. With reference to the new IND clearance, Cabaletta Bio has announced its intention to initiate a phase 1/2 clinical trial (NCT identifier pending) which will seek to enroll 6 patients with dermatomyositis, 6 patients with antisynthetase syndrome (ASyS), and 6 patients with immune-mediated necrotizing myopathy in separate parallel cohorts. The study will be open to patients aged 18 to 65 years who have continued to show evidence of disease activity following standard of care treatment. Patients with cancer-associated myositis, significant lung or cardiac impairment, those who have received prior treatment with a B-cell depleting agent within approximately 6 months, and those who have received prior treatment with a biologic agent within approximately 3 months will be excluded from participation. The participants in the open-label study will be administered a preconditioning regimen consisting of fludarabine and cyclophosphamide prior to receiving CABA-201.

The company noted that participants in the trial will receive a dose of 1x106 cells/kg of CABA-201, which was selected based on results from preclinical research on the CABA-201 binder and results published in The Lancet Rheumatology in February 2023 from the treatment of a patient with myositis who received a CD19-directed CAR-T construct for their disease.2 The Lancet Rheumatology results showed that the patient, who has the ASyS subtype, achieved a significant clinical response within 3 months that was sustained throughout a 6-month follow-up period.2 It was noted that during the follow-up period the patient experienced a repopulation of B-cells without evidence of disease recurrence.

The IND clearance comes approximately 2 months after CABA-201's initial IND clearance in March 2023 for a trial in patients with systemic lupus erythematosus (SLE) and lupus nephritis (LN).3 With reference to that IND clearance, the company announced that it is planning to initiate a phase 1/2 clinical trial (NCT identifier pending) which will seek to enroll a cohort of 6 patients with SLE with active LN and a separate cohort of 6 patients with SLE whose disease has no renal involvement.3,4 Both cohorts will be treated with a dose of 1x106 CAR-T cells/kg. In early May 2023, Cabaletta Bio also announced that CABA-201 had been granted fast track designation by the FDA.

“The clearance of our second IND application for CABA-201 within 2 months of the first IND clearance in SLE allows us to initiate a clinical trial in patients with myositis and underscores the efficiency of our organization along with the value of our experience in the development of cellular therapies for patients with autoimmune diseases,” Steven Nichtberger, MD, the CEO and co-founder of Cabaletta Bio, said in a statement.1 “Similar to our phase 1/2 trial design in SLE, this clinical trial will include patients with several different subtypes of myositis where B-cells may be involved in disease pathology. With an experienced team well-versed in conducting autoimmune-focused cell therapy trials, and a product candidate specifically engineered for patients with autoimmune diseases, we look forward to evaluating the potential for CABA-201 to change the treatment paradigm for patients with autoimmune diseases.”

1. Cabaletta Bio receives FDA clearance of IND application for CABA-201 for treatment of myositis. News release. Cabaletta Bio, Inc. May 16, 2023. Accessed May 31, 2023. https://www.cabalettabio.com/news-media/press-releases/detail/87/cabaletta-bio-receives-fda-clearance-of-ind-application-for
2. Cabaletta Bio reports fourth quarter and full year 2022 financial results and provides business update. News release. Cabaletta Bio, Inc. March 16, 2023. Accessed May 31, 2023. https://www.cabalettabio.com/news-media/press-releases/detail/80/cabaletta-bio-reports-fourth-quarter-and-full-year-2022
3. Cabaletta Bio receives FDA clearance of IND application for CABA-201 for treatment of systemic lupus erythematosus. News release. Cabaletta Bio, Inc. March 31, 2023. Accessed May 3, 2023. https://www.cabalettabio.com/news-media/press-releases/detail/81/cabaletta-bio-receives-fda-clearance-of-ind-application-for
4. Cabaletta Bio receives FDA fast track designation for CABA-201. News release. Cabaletta Bio, Inc. May 1, 2023. Accessed May 3, 2023. https://www.cabalettabio.com/news-media/press-releases/detail/84/cabaletta-bio-receives-fda-fast-track-designation-for
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