RESET-MG: Clinical Trial Evaluating Rese-cel (Resecabtagene Autoleucel), a Fully Human, Autologous 4-1BB-CD19-CAR T Cell Therapy in Generalized Myasthenia Gravis (gMG)
Ali Habib1, Stefan Ciurea1, Christina Ulane2, Ran Reshef2, Min Kang3, Madhav Seshadri3, David Richman4, Mehrdad Abedi4, Jonathan Hogan5, Yvonne White5, Jennifer Gresh5, Wayne Hull5, Thomas Furmanak5, Jenell Volkov5, Daniel Nunez5, Dan Thompson5, Jason Stadanlick5, Larissa Ishikawa5, Zach Vorndran5, Alexandra Ellis5, Steve Flanagan5, Mallorie Werner5, Justin Cicarelli5, Jazmean Williams5, Danielle Kobulsky5, Domenick Braccia5, Fatemeh Hadi-Nezhad5, Quynh Lam5, Samik Basu5, Raj Tummala5, David Chang5
1UC Irvine, 2Columbia University, 3UCSF, 4UC Davis, 5Cabaletta Bio
Objective:
RESET-MG (NCT06359041) is a Phase 1/2 trial evaluating the safety and efficacy of rese-cel in 2 independent cohorts of anti-AChR-antibody-positive and anti-AChR-antibody-negative gMG.
Background:

gMG is a B-cell-mediated disease; most patients have detectable autoantibodies targeting the neuromuscular junction. Most available therapies require chronic administration, increasing the risk of side effects, and many patients remain refractory despite several treatments. Rese-cel is an investigational, fully human, autologous 4-1BB CD19-CAR T cell therapy, designed to deeply and transiently deplete CD19+ B-cells following a single, weight-based infusion, potentially enabling an “immune reset” with durable responses.

Design/Methods:

Eligible patients are 18-70 years old with MGFA Classification II-IV gMG and MG-ADL ≥6 despite ≥2 prior/current treatments.

A single rese-cel infusion of 1x10^6 cells/kg is administered following standard preconditioning. All non-glucocorticoid immunomodulatory agents are discontinued by preconditioning; glucocorticoids are tapered post-infusion. Adverse events, gMG medications, gMG activity and translational endpoints are assessed.
Results:

As of September 2025, four patients (2 per cohort) have received rese-cel and completed ≥1 month follow-up. Grade 2 cytokine release syndrome occurred in 1 patient.

The 2 evaluable patients achieved MG-ADL improvements from 17 to 0 (achieving minimal symptom expression) and 14 to 7, off all gMG medications, at 20- and 8-weeks post-infusion, respectively. The 3rd patient is not evaluable due to use of a prohibited cytotoxic medication that may have inhibited CAR T activity; the 4th patient has insufficient follow up.

Rese-cel peaked by Day 14 and B-cells were depleted by Day 8 in all patients. Serum BAFF concentrations peaked following B-cell depletion. In the first treated patient, B-cells repopulated by Week 12 with predominantly transitional naïve cells (CD24++/CD38++). 

Conclusions:

These initial data suggest that rese-cel is well-tolerated and can cause immune reset in gMG, allowing patients to achieve meaningful clinical responses off gMG therapies. Both cohorts are fully enrolled, with post-treatment data forthcoming.

10.1212/WNL.0000000000215393
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