Cabaletta Bio’s CAR-T CABA-201 Receives Fourth IND Clearance, With New Trial Set for Myasthenia Gravis

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The CAR-T previously was cleared for separate trials in systemic lupus erythematosus, myositis, and systemic sclerosis.

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 from the FDA of its investigational new drug (IND) application for a clinical trial in generalized myasthenia gravis (gMG).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.1,2 In light of the IND clearance, Cabaletta Bio intends to carry out a phase 1/2 clinical trial that will seek to enroll 12 patients in total. The participants will be divided into 2 equally sized cohorts, 1 of which will include patients with acetylcholine receptor (AChR) antibody-positive gMG and the other of which will include patients with AChR antibody-negative gMG. The IND clearance marks the fourth IND clearance for CABA-201. Earlier in 2023, the CAR-T previously was cleared by the FDA for separate trials in systemic lupus erythematosus and lupus nephritis (LN); active idiopathic inflammatory myopathy (also referred to as myositis); and systemic sclerosis.2-4

“While we remain on track to deliver initial clinical data from CABA-201 treated patients with lupus and/or myositis in the first half of 2024, we are continuing to expand our CABA-201 portfolio beyond rheumatology and into neurology,” Steven Nichtberger, MD, the chief executive officer and co-founder of Cabaletta Bio, said in a statement.1 “The announcement of our fourth CABA-201 IND clearance is also our first IND clearance for the product candidate in a predominantly autoantibody mediated disease.”

Following a preconditioning regimen with fludarabine and cyclophosphamide, participants in the gMG trial will receive a 1-time dose of 1x106 cells/kg of CABA-201. The study will seek to recruit patients aged 18 to 70 years who still have gMG activity following treatment with current standard of care options. Patients who have exclusively ocular disease manifestation, thymoma that is active or untreated, or who have been treated with a B-cell-depleting therapeutic within the past 6 months will be excluded from participation.

Key Takeaways

  • Cabaletta Bio's investigational CAR-T therapy, CABA-201, has received FDA clearance for an investigational new drug (IND) application to conduct a clinical trial in generalized myasthenia gravis (gMG), marking the fourth IND clearance for CABA-201.
  • CABA-201 incorporates a 4-1BB costimulatory domain and aims to deplete B-cells, intending to "reset" the immune systems of patients; the phase 1/2 clinical trial for gMG will enroll 12 patients, with two cohorts, one for acetylcholine receptor (AChR) antibody-positive gMG and the other for AChR antibody-negative gMG.
  • The company is on track to deliver initial clinical data from CABA-201 trials treating lupus and/or myositis in the first half of 2024.

“Consistent with previously announced CABA-201 trials, the phase 1/2 clinical trial design for CABA-201 in gMG includes the same starting dose as used in the previously cleared clinical trials with CABA-201 and parallel cohorts of 6 patients,” Nichtberger continued.1 “While prioritizing delivery of initial clinical data in the first half of 2024 from our myositis and/or lupus trials, our clinical operations team is well positioned to execute the gMG program based on experience with MG sites in our legacy CAART platform. Despite recent advances with chronic, broadly immunosuppressive therapies, we believe there is an unmet need for a treatment option like CABA-201 that may provide a deep and durable, perhaps curative, outcome with a single dose in patients with gMG.”

CABA-201 is not the only CAR-T therapy currently under investigation for the treatment of MG. Notably, on November 13, 2023, Kyverna Therapeutics announced that it had received IND clearance from the FDA for an open-label, phase 2 clinical trial in 10 patients with MG for its CAR-T KYV-101.5 Similarly to CABA-201, KYV-101 is also being evaluated in patients with LN in the phase 1 KYSA-1 trial (NCT05938725) in the United States and the phase 1/2 KYSA-3 clinical trial in Germany. For patients with diffuse cutaneous systemic sclerosis, KYV-101 is being assessed in the phase 1/2 KYSA-5 trial (NCT identifier pending) in the US. Other CAR-T therapies in development for MG include IASO Biotherapeutics’ CT103A (equecabtagene autoleucel) and Cartesian Therapeutics’ Descartes-08.6,7

REFERENCES
1. Cabaletta Bio receives FDA clearance of CABA-201 IND application for treatment of generalized myasthenia gravis. News release. Cabaletta Bio, Inc. November 6, 2023. Accessed November 17, 2023. https://www.cabalettabio.com/news-media/press-releases/detail/99/cabaletta-bio-receives-fda-clearance-of-caba-201-ind
2. 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 November 17, 2023. https://www.cabalettabio.com/news-media/press-releases/detail/81/cabaletta-bio-receives-fda-clearance-of-ind-application-for
3. 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
4. Cabaletta Bio receives FDA clearance of IND application for treatment of systemic sclerosis with CABA-201. News release. Cabaletta Bio, Inc. November 6, 2023. Accessed November 17, 2023. https://www.cabalettabio.com/news-media/press-releases/detail/97/cabaletta-bio-receives-fda-clearance-of-ind-application-for
5. Kyverna Therapeutics cnnounces FDA Clearance of phase 2 IND for KYV-101, a fully human CD19 CAR T-cell therapy to treat Myasthenia Gravis. News release. Kyverna Therapeutics. November 13, 2023. Accessed November 17, 2023. https://www.prnewswire.com/news-releases/kyverna-therapeutics-announces-fda-clearance-of-phase-2-ind-for-kyv-101-a-fully-human-cd19-car-t-cell-therapy-to-treat-myasthenia-gravis-301986135.html
6. World's first CAR-T for NMOSD treatment, IASO Biotherapeutics' equecabtagene autoleucel, receives IND approval by NMPA. News release. IASO Biotherapeutics. August 19, 2022. Accessed November 17, 2023. http://www.iasobio.com/info.php?id=198
7. Cartesian Therapeutics announces dosing of first participant in a phase 2b randomized clinical trial for generalized myasthenia gravis. News release. Cartesian Therapeutics. January 31, 2023. Accessed November 17, 2023. https://www.cartesiantherapeutics.com/2023/01/31/cartesian-therapeutics-announces-dosing-of-first-participant-in-a-phase-2b-randomized-clinical-trial/
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