BACKGROUND: Linaprazan glurate, a potassium-competitive acid blocker, is in development for the treatment of erosive oesophagitis and other acid-related diseases. AIM: To evaluate the 4-week healing rate and safety of four linaprazan glurate dosing regimens in patients with erosive oesophagitis. METHODS: This double-blind, dose-finding study compared linaprazan glurate to lansoprazole. We included patients with endoscopically confirmed erosive oesophagitis (validated by a central review board) if they had Los Angeles (LA) grade C/D or LA grade A/B with partial response to at least 8 weeks of proton pump inhibitor therapy. Patients were randomised to 4 weeks of linaprazan glurate (25, 50, 75 or 100 mg twice daily) or lansoprazole (30 mg once daily), followed by 4 weeks of open-label lansoprazole. RESULTS: Of 248 patients randomised, central review confirmed erosive oesophagitis in 182 at screening endoscopy. Across all doses, linaprazan glurate achieved a 4-week healing rate of 71.1% in intention-to-treat (ITT) analysis and 80.9% in per protocol (PP) analysis. In comparison, lansoprazole achieved healing rates of 60.6% (ITT) and 59.1% (PPS). The best performing linaprazan glurate dosing group outperformed lansoprazole by 28% in patients with LA grade A/B with partial PPI response and by more than 50% in patients with LA grade C/D. CONCLUSIONS: Linaprazan glurate demonstrated high 4-week healing rates compared to lansoprazole, with a good safety profile, supporting its further development. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05055128; EudraCT: 2020-003319-91.