Minimal Symptom Expression with Active C1s Inhibition with Claseprubart

Topic:

Pre-Clinical Research

Poster Number: 218 M

Author(s):

Marek Smilowski, MD, Neurologia Śląska Centrum Medyczne, Katowice, Poland, Gilhus Nils Erik, MD, Haukeland University Hospital, Bergen, Norway, Maria Ait-Tihyaty, PhD, Dianthus Therapeutics, NY, USA, Caitlin Briggs, PhD, Dianthus Therapeutics, NY, USA, Uzma Siddiqui, MD, Dianthus Therapeutics, NY, USA, Luke Hickey, MSc, Dianthus Therapeutics, NY, USA, Marianna Lalla, MD, Dianthus Therapeutics, NY, USA, Said Beydoun, MD, University of Southern California, CA, USA

Objective
To assess minimal symptom expression (MSE) in AChR+ generalized myasthenia gravis (gMG) patients treated with claseprubart.

Background
The classical complement pathway plays a significant role in gMG pathology. 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 clinically validated complement target. Reaching remission state is an important goal for patients with gMG and their treating physicians, thus achieving MSE with claseprubart is a key efficacy objective.

Methods
MaGic (NCT06282159), is a global Phase 2, randomized, double-blind, placebo-controlled trial (RCT). Patients treated with claseprubart (300mg, Q2W) were evaluated for MSE (MG-ADL ≤1 or QMG ≤3) compared to placebo patients. p-values are one-sided, with nominal significance assessed at an alpha of 0.1. Outcomes include proportion of patients achieving MSE at Week 13 and anytime during the study; earliest timepoint of MSE achievement, and durability defined as sustained MSE for at least 6 weeks.

Results
At Week 13, 37% of patients treated with claseprubart achieved MG-ADL-MSE versus 14% with placebo (OR 3.81; p=0.0550). 43% achieved MG-ADL-MSE at least once during the RCT versus 14% of placebo (OR: 4.72; p=0.0231). This effect was observed as early as Week 1, with a median time to response at Week 3. A sustained remission-like state (for at least 6 weeks) was seen in all patients who achieved MSE. Similar results were observed using QMG minimum symptom expression threshold.

Conclusions
Claseprubart patients were more than four times more likely to achieve MSE than placebo patients with MSE being observed as early as Week 1. Patients who achieved MSE maintained the response for at least 6 weeks. Altogether these results highlight the therapeutic potential of aC1s inhibition in AChR+ gMG.