Abstract Objectives The study was designed to obtain a preliminary assessment of the safety and efficacy of SGX945 (dusquetide) for the treatment of aphthous oral and genital ulcers in Behçet’s syndrome. Methods This was an open-label pilot study of intravenous dusquetide in patients with Behçet’s syndrome who had at least two active oral and/or one active genital ulcer(s) at enrolment. Participants were treated twice weekly for 4 weeks and then followed for an additional 4 weeks. Efficacy assessments included number and pain of oral and genital ulcers, overall disease activity assessed using Behçet’s Syndrome Current Activity Form and Behçet’s Syndrome Activity Scale and health-related quality of life assessed using Behçet’s Syndrome Quality of Life Index. Results Eight participants with oral ulcers were enrolled. Seven of eight participants reported a perceived benefit including reduction in number, duration and pain of oral ulcers. Comparison to historical placebo groups demonstrated a reduction in the number of ulcers, time to resolution of ulcers, area under the curve of the ulcer-days, oral pain and baseline quality of life metrics. The treatments were well-tolerated with no treatment-related AEs and no serious or severe adverse events recorded. Conclusion This small pilot study illustrates the potential efficacy and tolerability of SGX945 in patients with Behçet’s syndrome who had ulcers despite being on colchicine maintenance therapy. The results justify further development of SGX945 for the treatment of Behçet’s syndrome. Clinical trial registration Clinicaltrials.gov, http://clinicaltrials.gov, NCT06386744.