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