Cabaletta Bio’s CAR-T CABA-201 Effects Clinical Responses in Autoimmune Diseases
Clinical responses were reported in patients with lupus and myositis.
Cabaletta Bio’s CABA-201, an investigational CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy intended to treat various indications, has effected responses or possible emerging responses in some patients treated in the phase 1/2 RESET-SLE clinical trial (NCT06121297) for systemic lupus erythematosus (SLE) and lupus nephritis (LN), the phase 1/2 RESET-Myositis clinical trial (NCT06154252) for active idiopathic inflammatory myopathy (IIM), and the phase 1/2 RESET-SSc clinical trial (NCT06328777) in systemic sclerosis (SSc).1 These data were presented at the 2024 American College of Rheumatology (ACR) Convergence, held November 14 to 19 in Washington, DC.
Cabaletta reported that in RESET-Myositis, a patient with immune-mediated necrotizing myopathy (IMNM) who has 6 months of follow-up showed a sustained and improved clinical response without flares, and was off of immunosuppressants. Another patient with IMNM and 1 month of follow-up showed a total improvement score in line with the aforementioned patient and was also off immunosuppressants at 1 month posttreatment. A patient with dermatomyositis achieved a major total improvement score response and was off immunosuppressants at 1 month posttreatment. This patient also showed an improvement to normal in muscle strength and improved from 25 to 9 on the Cutaneous Dermatomyositis Disease Area and Severity Index – Activity.
In RESET-SLE, 3 patients with nonrenal SLE had no clinical symptoms on the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) 2000 at their latest follow-up. The first patient in this group to have been treated also finished tapering off of prednisone. A patient with LN improved from 22 to 8 on SLEDAI from baseline to 4 months of follow-up. The patient’s proteinuria also approached normal levels, constituting an improvement of greater than 90%. This patient, who is off immunosuppressants, is in the process of tapering off prednisone.
At 42 days posttreatment, a patient treated in RESET-SSc, who is part of the study’s severe skin cohort, achieved an improvement to a score of 36 on the modified Rodnan Skin Score, down from a baseline score of 42. Cabaletta stated that this patient, who has ceased receiving disease-specific therapy, may be showing an emerging drug-free clinical response.
In terms of safety, no cases of cytokine release syndrome (CRS) were reported in 5 of 8 evaluable patients across the 3 clinical trials. The other 3 evaluable patients had CRS cases that were graded as 1 to 2 and did no require the use of tocilizumab. The 3 patients recovered after receiving standard treatment. The first patient with LN treated in RESET-SLE experienced a case of immune effector cell-associated neurotoxicity syndrome (ICANS) that Cabaletta originally reported in August 2024. Cabaletta pointed out that the patient showed signs of a possible occult infection, including acute inflammatory events that took place prior to receiving the CAR-T and an abnormal and proinflammatory cytokine profile that was maintained before and after receiving the CAR-T.
“The clinical data reported at ACR Convergence this weekend support the potential of the current dose of CABA-201 to provide immunosuppressant-free, compelling clinical responses in patients with active, refractory autoimmune disease,” David J. Chang, MD, the chief medical officer of Cabaletta, said in a statement.1 “Data presented from the previously reported patient with LN who experienced ICANS and had acute inflammatory events shortly before CABA-201 treatment demonstrated an abnormal, proinflammatory cytokine profile prior to and after CABA-201 infusion, suggestive of an occult infection. As a result of these data, subjects in the RESET clinical program who develop a fever prior to scheduled infusion will wait a minimum of 2 weeks before administration of CABA-201. Other than this patient with a second, later peak expansion, CABA-201 displayed a consistent PK and PD profile in all other patients. In addition to our promising clinical and translational data set from the RESET program, we believe our efficient clinical trial design, growing footprint of 40 actively recruiting US clinical sites and anticipated expansion into Europe in 2025 provide us with a differentiated opportunity to accelerate development of CABA-201 for patients. Data permitting, we anticipate meeting with the FDA in 2025 to discuss potential registrational trial designs for CABA-201 that will allow us to bring the therapeutic potential of this investigational therapy closer to autoimmune patients.”
In addition to the aforementioned trials, CABA-201 has also received clearance from the FDA for a phase 1/2 clinical trial (RESET-MG; NCT06359041) in generalized myasthenia gravis.2 In May 2024, Cabaletta also announced that it will be incorporating use of CABA-201 as a monotherapy into a substudy (RESET-PV, NCT04422912) within its phase 1 DesCAARTes clinical trial for DSG3-CAART, an autologous Desmoglein 3 chimeric autoantibody receptor T-cell (CAART) therapy being evaluated for pemphigus vulgaris. Earlier in November 2024, Cabaletta reported that in total 16 patients have been enrolled in the RESET clinical trials and that 10 patients have been dosed.3 The company also noted that a clinical trial application cleared by the European Medicines Agency for CABA-201 in lupus would allow for expansion of clinical development for the CAR-T into Europe.
“Focused clinical execution has resulted in 40 US clinical sites actively recruiting patients for the RESET clinical trial program for CABA-201...” Steven Nichtberger, MD, the CEO of Cabeletta, said in a November 2024 statement.3 “We are encouraged by the accelerating pace of enrollment and, data permitting, anticipate meeting with the FDA next year regarding registrational program designs for CABA-201.”
REFERENCES
1. Cabaletta Bio presents positive clinical safety and efficacy data on CABA-201 at ACR Convergence 2024. News release. Cabaletta Bio, Inc. November 18, 2024. Accessed November 27, 2024. https://www.cabalettabio.com/news-media/press-releases/detail/119/cabaletta-bio-presents-positive-clinical-safety-and
2. Cabaletta Bio reports first quarter 2024 financial results and provides business update. News release. Cabaletta Bio, Inc. May 15, 2024. Accessed November 27, 2024. https://www.cabalettabio.com/news-media/press-releases/detail/110/cabaletta-bio-reports-first-quarter-2024-financial-results
3. Cabaletta Bio Reports Third Quarter 2024 Financial Results and Provides Business Update. News release. Cabaletta Bio, Inc. November 14, 2024. Accessed November 27, 2024. https://www.cabalettabio.com/news-media/press-releases/detail/112/cabaletta-bio-reports-positive-initial-clinical-data-from
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