LB-001 Hemera-1 (CarboxyHEMoglobin OxygEn delivery for revascularization in acute stroke) multicenter prospective trial: safety of PP-007 and efficacy on propensity score analysis in acute ischemic stroke patients undergoing mechanical thrombectomy

<h3>Background</h3> Mechanical Thrombectomy (MT) has revolutionized the outcome of stroke secondary to large artery occlusion (LVO). However, despite high rates of recanalization achieved by MT, the proportions of patients with 90 days mRS post stroke is still lacking behind. PEGylated Bovine Carboxyhemoglobin-based oxygen and carbon monoxide delivery (PP-007) has demonstrated ability to increase blood flow in the leptomeningeal anastomosis (LMA), improve oxygen delivery, ultimately protecting the ischemic penumbra and slow down core progression. Efficacy of this compound has been demonstrated in several animal models of experimental ischemia. Safety of PP 007 in patients with LVO undergoing MT has been described in a phase 1 clinical Trial (HEMERA 1 CarboxyHEMoglobin oxygEn delivery for Revascularization in Acute Stroke; ClinicalTrials.gov NCT04677777). <h3>Methods</h3> In an extension of the Phase 1, subjects with AIS undergoing MT and/or intravenous (IV) tissue plasminogen activator (tPA) or Tenecteplase (TNK) were enrolled to receive PP-007. In another extension of phase 1, subjects with AIS undergoing MT received 2 consecutive doses of PP-007. Safety in these two Phase 1 extensions were adjudicated by an independent Data Monitoring Safety Board (DSMB) and an independent imaging core lab. Subsequently, a Propensity Score Matching (PSM) analysis of all subjects with LVO who underwent MT and received PP-007 was conducted vs. matched controls from the University of Pittsburg Medical Center (UPMC) stroke database. <h3>Results</h3> Adverse events were comparable between PP-007+Standard of Care (SOC) versus SOC alone. Pharmacokinetic analysis in these patients revealed sustainable levels of PP-007 up to 24h. With regards to efficacy, functional independence (mRS 0-2) was achieved in 63.6%, 77.8%, and 61.1% of patients who received PP-007 in Parts 1-3, respectively. This was statistically significantly superior to the 32.9% of patients who achieved 90 days mRS 0-2 of the 70 matched controls with LVO who underwent MT from UPMC debase. Overall, the 35 patients treated with PP-007 and MT enrolled in achieved significantly higher functional independence vs matched controls (65.7% vs. 32.9%, OR3.92 [95% CI: 1.66-9.24], p=0.002). <h3>Conclusions</h3> IV administration of PP-007 was well tolerated by acute stroke patients undergoing MT including patients who received IV tPA or TNK and patient who received two consecutive doses of the agent. In addition, clinical outcomes were significantly better compared to matched controls showing potential benefit of PP-007 in LVO stroke patients. HEMERA 2 has received fast-track designation for Phase 3 adaptive design by the FDA. <h3>Disclosures</h3> <b>I. Linfante:</b> 4; C; Prolong Pharmaceuticals. <b>W. Clarke:</b> None. <b>D. Haussen:</b> None. <b>E. Lin:</b> None. <b>D. Liebeskind:</b> 2; C; Prolong Pharmaceuticals. <b>M. Doheim:</b> None. <b>R. Jubin:</b> 5; C; Prolong Pharmaceuticals. <b>S. Pandya:</b> 5; C; Prolong Pharmaceuticals. <b>K. Gruis:</b> 5; C; Prolong Pharmaceuticals. <b>G. Dabus:</b> None. <b>R. Nogueira:</b> 2; C; Prolong Pharmaceuticals.