{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T15:05:33Z","timestamp":1789398333351,"version":"build-2803163510"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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\u20131200 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial registration<\/jats:title>\n                    <jats:related-object>\n                      <jats:ext-link>https:\/\/clinicaltrials.gov\/<\/jats:ext-link>\n                      , identifier NCT06553209.\n                    <\/jats:related-object>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1811041","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T10:48:35Z","timestamp":1779965315000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["First-in-human, phase 1 study of CM512, a TSLP\/IL-13 bispecific antibody, in healthy volunteers: safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity"],"prefix":"10.3389","volume":"17","author":[{"given":"Yue","family":"Cheng","sequence":"first","affiliation":[{"name":"Clinical Trial Center and National Medical Products Administration Key Laboratory for Clinical Research and Evaluation of Innovative Drugs, West China Hospital of Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingfeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, West China Hospital of Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengmeng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, West China Hospital of Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of 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