ABSTRACT NUMBER: ESOC2026OT21 RATIONALE AND DESIGN OF A MULTI-DOSE REGIMEN OF ODATROLTIDE (LT3001) FOR ACUTE ISCHEMIC STROKE WITHIN 24 HOURS: THE LT3001-206 MECHANISTIC STUDY

Abstract Background and aims Patients with acute ischemic stroke (AIS) and disabling symptoms face limited treatment options beyond the 4.5-hour window. Odatroltide (LT3001) is a novel molecule designed to enhance endogenous fibrinolysis and scavenge free radicals. Pooled safety data from three Phase 2 trials (N=408) demonstrated a 0% treatment-related symptomatic intracranial hemorrhage (sICH) rate. Previous efficacy signals in specific subgroups—including large artery atherosclerosis (LAA) and mismatch-positive patients—showed that Odatroltide achieved an absolute increase of >10% in favorable mRS outcomes compared to the placebo group. These findings justify an intensive multi-dose approach to maximize overall treatment benefit. Methods The LT3001-206 study aims to provide mechanistic proof-of-concept for the drug’s fibrinolytic activity by evaluating intracranial arterial recanalization rates in humans using an intensive 3-day multi-dose regimen. Results LT3001-206 is an open-label, single-arm exploratory trial involving ~10 evaluable AIS patients. Participants within 24 hours of stroke symptom onset who are ineligible for standard reperfusion therapies will receive 0.05 mg/kg Odatroltide twice daily (BID) for 3 consecutive days (6 total doses). Conclusions The primary efficacy outcome is the successful recanalization rate of the target occluded artery, assessed via longitudinal CTA/MRA imaging at screening, Day 1 and Day 7. Safety outcomes include sICH incidence within 36 hours and serious adverse events through 30 days. Conflict of interest