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Background: Batefenterol is a novel bifunctional muscarinic antagonist β 2 -agonist in development for COPD. The primary objective of this randomized, double-blind, placebo-controlled, active comparator, Phase IIb study was to model the dose-response of batefenterol and select a dose for Phase III development., Patients and Methods: Patients aged ≥40 years with COPD and FEV 1 ≥30% and ≤70% predicted normal were randomized equally to batefenterol 37.5, 75, 150, 300, or 600 µg, placebo, or umeclidinium/vilanterol (UMEC/VI) 62.5/25 µg once daily. The primary and secondary endpoints were weighted-mean FEV 1 over 0-6 hours post-dose and trough FEV 1 , analyzed by Bayesian and maximum likelihood estimation E max of dose-response modeling, respectively, on day 42., Results: In the intent-to-treat population (N=323), all batefenterol doses demonstrated statistically and clinically significant improvements from baseline vs placebo in the primary and secondary endpoints (191.1-292.8 and 182.2-244.8 mL, respectively), with a relatively flat dose-response. In the subgroup reversible to salbutamol, there were greater differences between batefenterol doses. Lung function improvements with batefenterol ≥150 µg were comparable with those with UMEC/VI. Batefenterol was well tolerated and no new safety signals were observed., Conclusion: Batefenterol 300 µg may represent the optimal dose for Phase III studies., Competing Interests: Disclosure The authors declare the following real/perceived conflicts of interest: C Crim, MLW, C Crawford, CB, and RC-S are GSK employees and hold shares in GSK; SH holds shares in GSK; EDB has received fees from Novartis, Cipla, Sanofi Regeneron, AstraZeneca, ALK, and Boehringer Ingelheim for advisory board membership, fees from Novartis for participation in speakers’ bureau, fees from Vectura and Actelion for consultancy work, fees from Cipla, Menarini, ALK, AstraZeneca, and Boehringer Ingelheim for lectures, and fees from ICON for participation on a study oversight steering committee, and his institution has received funding from Boehringer Ingelheim, Merck, Takeda, GSK, Hoffman le Roche, Actelion, Chiesi, Sanofi-Aventis, Cephalon, TEVA, Novartis, and AstraZeneca for participation in clinical trials. EMK has participated in advisory boards, speaker panels, or received travel reimbursement from Amphastar, AstraZeneca (Pearl), Forest, Novartis, Sunovion, Teva, and Theravance, has participated in medical advisory boards for Mylan and Oriel, and has performed consulting for Oriel and GSK. GJF’s institution has received funding from GSK for participation in clinical trials; KP and IS report no conflicts of interest in this work.