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June 1, 2026Open Access

First-in-human, phase 1 study of CM512, a TSLP/IL-13 bispecific antibody, in healthy volunteers: safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity

YCYue ChengNational Medical Products Administration QLQ F LiuNorthwestern Polytechnical University MLM LiSichuan University

Key Points

This study aims to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of CM512 in healthy individuals.
First-in-human, randomized, double-blind, placebo-controlled trial
Enrolled 64 healthy participants across two phases: SAD (n=40) and MAD (n=24)
Administered subcutaneous doses of CM512 or placebo in sequential cohorts with varying dosages.
CM512 was well tolerated, with treatment-emergent adverse events occurring in 71.9% of SAD and 68.8% of MAD participants.
Showed linear, dose-proportional pharmacokinetics with a long half-life of 58.7 to 73.6 days.
Significantly reduced levels of free TSLP and IL-13, as well as inflammation biomarkers such as IgE and eosinophils compared to placebo.

Abstract

Purpose Type 2 chronic inflammatory diseases (e.g., atopic dermatitis and allergic rhinitis) impose a substantial global burden with unmet medical needs. Thymic stromal lymphopoietin (TSLP) and interleukin-13 (IL-13) are key pathogenic drivers, and bispecific antibodies targeting both cytokines may offer synergistic clinical benefits. CM512 is a novel recombinant bispecific antibody targeting both TSLP and IL-13 with high affinity. This first-in-human, randomized, double-blind, placebo-controlled phase 1 study evaluated the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of single (SAD) and multiple ascending doses (MAD) of subcutaneous CM512 in healthy adults. Methods The SAD phase enrolled 40 healthy participants across four sequential cohorts (150, 450, 900, and 1200 mg), randomized 4:1 to receive subcutaneous CM512 or placebo per cohort. The MAD phase enrolled 24 participants across two sequential cohorts (150 and 600 mg biweekly), randomized 2:1 per cohort. The primary endpoint was safety and tolerability; secondary endpoints included PK, PD, and immunogenicity. Results CM512 was well tolerated. Treatment-emergent adverse events (TEAEs) occurred in 71.9% (23/32) and 68.8% (11/16) of CM512 recipients in the SAD and MAD phases, with incidence comparable to placebo. All treatment-related TEAEs were mild or moderate. No serious adverse events, TEAEs leading to withdrawal, or deaths were reported. In the SAD phase, CM512 displayed linear, dose-proportional PK from 150–1200 mg, accompanied by a long terminal half-life (mean range: 58.7-73.6 days). In the MAD phase, biweekly administration resulted in accumulation (mean accumulation ratio: 2.50-3.17), consistent with its long half-life. CM512 significantly reduced free TSLP and IL-13, and sustainedly lowered blood eosinophils, IgE, and thymus activation-regulated chemokine (TARC) levels versus placebo. The incidence of treatment-emergent anti-drug antibodies in healthy participants receiving CM512 was low, at 3.1% (1/32) in the SAD phase and 0% (0/16) in the MAD phase, respectively. Conclusion CM512 demonstrated favorable safety, linear PK, and low immunogenicity in healthy participants. It significantly reduced free target cytokines and type 2 inflammation biomarkers, supporting further clinical investigation for type 2 inflammatory diseases. Clinical trial registration https://clinicaltrials.gov/ , identifier NCT06553209.

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