To assess the safety and efficacy of claseprubart in adults with acetylcholine receptor antibody positive (AChR Ab+) generalized Myasthenia Gravis (gMG).

The classical complement pathway plays a significant role in the pathogenesis of gMG. Claseprubart is an investigational, clinical-stage, potent monoclonal antibody engineered to selectively target the classical pathway by inhibiting only the active form of the C1s protein (aC1s), a validated complement target. The MaGic study is the first study investigating the therapeutic potential of aC1s inhibitor in gMG.

MaGic (NCT06282159) is a randomized, double-blind, placebo-controlled Phase 2 study.  Sixty-five participants with AChR Ab+ gMG were enrolled and randomized 1:1:1 to receive: claseprubart 300mg (Q2W), claseprubart 600 mg (Q2W), or placebo for 13 weeks, followed by an ongoing 52-week open-label extension and 40-week safety follow-up. Endpoints at 13 weeks included safety, tolerability, efficacy (MG activities of daily living [MG-ADL], Quantitative MG score [QMG], Minimal Symptom Expression [MSE] and MG Composite scale [MGC].

Claseprubart was well tolerated with no serious adverse events, no serious bacterial infections, and no autoimmune activation. Injection site reactions were infrequent, mild to moderate, with the majority mild. At Week 13, claseprubart 300mg arm improved MG-ADL by 4.6 from baseline (P=0.0113); 5.4 (P=0.0006) for claseprubart 600mg; versus 2.8 for placebo (no significant difference between active treatment arms). Significant improvement in MG-ADL was observed as early as Week 1. At Week 13, claseprubart 300mg improved QMG by 4.4 (P=0.0144) vs 2.0 for placebo; claseprubart 600mg improved QMG by 4.5 (P=0.0111); MSE was achieved by 37% (300mg) and 27% (600 mg) vs 14% placebo; MGC for 300 mg: 8.7 (P=0.0008), 600 mg: 8.6 (P=0.0008) vs 3.1 placebo.

With a favorable safety profile, claseprubart demonstrated rapid, statistically significant, and clinically meaningful improvements in MG-ADL, QMG, MGC. Phase 3 study in gMG is in planning.