ABSTRACT NUMBER: ESOC2026A889 A FIRST-IN-CLASS, LONG-ACTING IGF-1 NEUROPROTECTANT FOR ACUTE ISCHEMIC STROKE

Abstract Background and aims The mechanism of acute ischemic stroke (AIS) is complex. There is currently no effective neuroprotective therapy for AIS. GenSci155, a first-in-class long-acting IGF-1, is in development for treatment of AIS. Here, we investigated the potential neuroprotective effects of GenSci155 in vitro and in vivo. Methods In SH-SY5Y cells, Gensci155 effects on oxidative stress were studied. In the transient middle cerebral artery occlusion (MCAO) model in SD rats, at the time of reperfusion, tMCAO rats were i.v. dosed with GenSci155 (9, 12 and 25 mg/kg) or edaravone dexborneol (3.75 mg/kg). The infarct volume was assessed by histology 24 hours after ischemia. Drug levels were quantified in both injured and intact hemisphere. Results In vitro, GenSci155 improved the survival of SH-SY5Y cells injured by H2O2. In the tMCAO model, GenSci155 demonstrated a significant dose-related reduction of infarct size (p<0.01), while a trend was observed in the edaravone dexborneol group (p=0.06). GenSci155 accumulated preferentially in the injured hemispheres at levels ~30-fold higher than that of the intact hemisphere. No treatment-related safety signals were observed in the GenSci155 group throughout the study period. Conclusions GenSci155 significantly reduced infarct volume compared with edaravone dexborneol group, possibly via the protection against oxidative stress during reperfusion. Coupled with the higher exposure in the injured hemisphere, these results demonstrated therapeutic potential for GenSci155 to treat AIS. IND-enabling activities are ongoing to validate efficacy and safety in clinical setting planned in 2026. Conflict of interest All authors: nothing to disclose