ABSTRACT NUMBER: ESOC2026A795 EFFICACY OF ODATROLTIDE (LT3001) IN DISABLING AND MODERATE-TO-SEVERE ACUTE ISCHEMIC STROKE: POOLED ANALYSIS OF TWO PHASE 2 TRIALS

Abstract Background and aims Patients with AIS and disabling symptoms face limited treatment options beyond the 4.5-hour window. Odatroltide is a novel agent designed to provide targeted fibrinolysis and neuroprotection via free radical scavenging. We evaluated its efficacy across two Phase 2 trials focusing on moderate-to-severe and clinically disabled stroke populations. Methods Data were analyzed from two randomized, placebo-controlled trials: Study 202 (N=297) and Study 205 (N=88). Key subgroups included disabling motor features, baseline NIHSS 7–10, large artery atherosclerosis (LAA), and perfusion mismatch. Disabling symptoms were defined as NIHSS arm motor or leg motor scores >2. The primary outcome was favorable functional recovery (mRS 0–1 or 0–2) at 90 days. Results In Study 202, Odatroltide showed consistent gains in moderate strokes (NIHSS 7–10), with a +9% absolute improvement in mRS 0–2 versus placebo. In the LAA subgroup, absolute gains over placebo were +9% for mRS 0–1 and +11% for mRS 0–2. For patients with specific motor disabilities, absolute gains in mRS 0–1 reached +24% in those with arm motor drift and +14% in those with leg motor drift. In Study 205, mismatch-positive patients showed numerical improvements of +7% in mRS 0–1 and +10% in mRS 0–2 versus placebo. Conclusions Odatroltide demonstrated efficacy signals in biology-aligned populations, particularly in those with disabling motor deficits, LAA, or perfusion mismatch. These findings suggest that Odatroltide may offer a therapeutic option for moderate-to-severe stroke patients currently ineligible for standard reperfusion. Conflict of interest Name of author: nothing to disclose