To report the preclinical development of MGAC-007, a novel Antigen Drug Conjugate (AgDC) designed for the treatment of Acetylcholine receptor–positive Myasthenia Gravis (AChR? MG).

AChR? MG is an antibody-mediated autoimmune disorder in which a small fraction of B cells produces anti-AChR antibodies that impair neuromuscular transmission and cause fluctuating weakness. Current treatments rely on chronic immunosuppression, increasing infection and malignancy risk while failing to address the disease’s root cause. Canopy Immuno-Therapeutics developed AgDCs: biologics which employ two complementary mechanisms of action (MoA) that specifically sequester pathogenic autoantibodies (MoA1) and selectively eliminate their autoreactive B-cell sources (MoA2), while preserving protective immunity. MGAC-007, Canopy’s lead AgDC, is advancing to a Phase I clinical trial in patients with AChR? MG in 2026.

Ex vivo, in vitro, and in vivo studies were conducted to characterize MGAC-007’s functional activity across its dual mechanisms of action, including assays for autoantibody depletion, B-cell receptor (BCR) binding and cytotoxicity, and potency evaluation in MG animal models.

In ex vivo assays using sera from AChR? MG patients, MGAC-007 selectively depleted a median of 73% of pathogenic anti-AChR antibodies while preserving protective titers. In vitro, MGAC-007 selectively lysed AChR-reactive hybridoma cells in a BCR-dependent manner, while sparing unrelated BCR clones. In a passive-transfer myasthenic crisis rat model, MGAC-007 reduced circulating pathogenic antibodies by up to 90% within two hours, restored motor function, reduced mortality by 85–100% and normalized muscle histology versus controls. Furthermore, pretreatment with MGAC-007 reduced the AChR-specific titer of mice immunized with AChR by up to 73%, confirming targeted depletion of AChR-specific B cells with autoreactive potential.

Preclinical data strongly support the continued development of MGAC-007, which demonstrates proof-of-concept safety & efficacy as a first-in-class therapy for AChR? MG. Its potential as a targeted immunotherapy will be further evaluated in an upcoming multinational Phase I clinical trial.