CM512 bispecific antibody safely reduces TSLP, IL-13, and inflammatory markers in healthy volunteers

Type 2 chronic inflammatory diseases, such as atopic dermatitis and allergic rhinitis, represent a significant global health burden with substantial unmet medical needs. Thymic stromal lymphopoietin (TSLP) and interleukin-13 (IL-13) are recognized as pivotal pathogenic drivers in these conditions. Current therapies often target individual cytokines, but a bispecific antibody simultaneously neutralizing both TSLP and IL-13 could offer synergistic clinical benefits by more comprehensively dampening the inflammatory cascade.

This first-in-human, randomized, double-blind, placebo-controlled Phase 1 study evaluated single (SAD) and multiple ascending doses (MAD) of subcutaneous CM512 in healthy adults. The SAD phase enrolled 40 participants across four cohorts, randomized 4:1 to receive CM512 150, 450, 900, or 1200 mg subcutaneously. The MAD phase enrolled 24 participants across two cohorts, randomized 2:1 to receive CM512 150 or 600 mg biweekly subcutaneously. Primary endpoints focused on safety and tolerability, with secondary endpoints assessing pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity.

CM512 was well tolerated, with treatment-emergent adverse events (TEAEs) occurring in 71.9% (23/32) of CM512 recipients in the SAD phase and 68.8% (11/16) in the MAD phase, comparable to placebo. All treatment-related TEAEs were mild or moderate, with no serious adverse events, withdrawals, or deaths reported. In the SAD phase, CM512 exhibited linear, dose-proportional PK from 150-1200 mg, characterized by a long terminal half-life (mean range: 58.7-73.6 days). Biweekly MAD administration resulted in accumulation (mean accumulation ratio: 2.50-3.17), consistent with its extended half-life.

CM512 significantly reduced free TSLP and IL-13 levels, and sustainedly lowered blood eosinophils, IgE, and thymus activation-regulated chemokine (TARC) levels compared to placebo.