Abstract Number: Esoc2026lb208 Arpeggio Trial of Scp776 Adjunctive to Thrombectomy: Efficacy Patterns in a Late Window Phase 2a Population

Abstract Background and aims Scp776 is a first-in-class cytoprotective biologic that binds phosphatidylserine on injured cells to deliver IGF-1 as an adjunct to endovascular thrombectomy (EVT). In the ARPEGGIO phase 2a trial, scp776 showed a reasonable safety profile with directionally favorable effects on discharge NIHSS, final infarct volume (FIV), and 90-day modified Rankin Scale (mRS). We present heterogeneity of treatment effect (HTE) analyses examining interactions between treatment and reperfusion timing, as well as other baseline characteristics. Methods ARPEGGIO was a multicenter, randomized, double-blind, placebo-controlled, dose selection phase 2a study of patients with large-vessel occlusion ischemic stroke intended for EVT without intravenous thrombolysis. Longitudinal analyses of serial NIHSS and imaging data were conducted. In addition, HTE analyses examined treatment-by-covariate interactions for the expanded scp776 dose level versus placebo, focusing on reperfusion timing and baseline imaging characteristics. Sensitivity analyses assessed robustness. Endpoints included discharge NIHSS, final infarct volume, and 90-day mRS. Results In the primary contrast of placebo (n = 48) vs. the expanded scp776 dose level (n = 40), a treatment-by-reperfusion timing interaction was observed. Exploratory time-stratified analyses showed concordant treatment effects across FIV, discharge NIHSS, and 90-day mRS. Sensitivity analyses supported robustness. Longitudinal analyses and HTE results will be presented for this population. Conclusions At the selected dose level, reperfusion timing appears to modify the treatment effect of scp776, with signals of greater benefit in the later-presenting enrolled patients. These exploratory findings warrant prospective evaluation and may have implications for patient selection in future trials. Conflict of interest