ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Translational Pharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1647816
Safety,Tolerability,Pharmacokinetics,Immunogenicity and Pharmacodynamics of 9MW1911, an Anti-ST2 Monoclonal Antibody: Results from a First-in-Human Phase 1 Study
Provisionally accepted
Qian Zhao1,2
Qian Li1,2Yucan Wang1,2Li Li2,3
Xue Zhao1,2Ni Wu1,2Diyi Fu1,2
Danfeng Yin4
Jing Feng4Zhitian Hu4Yinhan Guo4
Rui Chen1,2*- 1Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Beijing, China
- 2Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- 3Clinical Pharmacology Research Center, Peking Union Medical College Hospital,, Beijing, China
- 4Mabwell Shanghai Biotechnology Co Ltd, Shanghai, China
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Background: 9MW1911 is a high-affinity human IgG4 monoclonal antibody targeting ST2, the human IL-33 receptor. It may have anti-inflammatory effects by blocking the IL-33/ST2 pathway. This first-in-human trial (NCT05803902) aimed to evaluate the safety, tolerability, pharmacokinetics, immunogenicity and pharmacodynamics of 9MW1911 in healthy participants.Methods: This phase Ⅰ, randomized, double-blind, placebo-controlled study enrolled 48 healthy adults. After a screening period of up to 28 days, they received a single ascending intravenous dose (ranging from 25 to 1200mg) of 9MW1911 (n=6 per dose) or matched placebo (n=2 per dose). Parameters of safety, pharmacokinetics, immunogenicity and pharmacodynamics were evaluated, with follow-up visits until day 113 post-dosing.Results: 9MW1911 was safe and well-tolerated across various doses. Most AEs were of mild to moderate ,resolved without treatments. No dose-related AEs were observed, and the only serious AE (fetal malformation) was deemed unrelated to the study drug.No deaths or discontinuations due to AEs occurred. 9MW1911 showed linear serum pharmacokinetics at 100 -1200mg. No anti-drug antibodies were detected in any participants. Total sST2 in serum increased and stabilized at higher dose levels, demonstrating sustained target binding.The study demonstrates that 9MW1911 was safe and well-tolerated in healthy participants, with a linear serum pharmacokinetic profile across higher dose levels. Sustained elevation of sST2 levels suggested target binding. These data support the continued development of 9MW1911 for the therapeutic use in the relevant disease.
Keywords: 9MW1911, Safety, pharmacokinetics, First-in-human trial, ST2
Received: 17 Jun 2025; Accepted: 30 Jul 2025.
Copyright: © 2025 Zhao, Li, Wang, Li, Zhao, Wu, Fu, Yin, Feng, Hu, Guo and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Rui Chen, Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Beijing, China
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