Efficacy and Safety of Nerinetide in Participants With Acute Ischemic Stroke Undergoing Endovascular Thrombectomy Excluding Thrombolysis

Inclusion Criteria:

1. Acute ischemic stroke (AIS) selected for emergency endovascular treatment.

2. Age 18 years or greater.

3. Onset (last-known-well) time to randomization time within 12 hours.

4. Disabling stroke defined as a baseline National Institutes of Health Stroke Score (NIHSS):

5. NIHSS > 5 for internal carotid artery (ICA) and M1-middle cerebral artery (MCA)occlusion; or

6. NIHSS > 10 for M2-MCA occlusion.

7. Confirmed symptomatic intracranial occlusion at one or more of the followinglocations: Intracranial carotid I/T/L, M1 or M2 segment MCA. Tandem extracranialcarotid and intracranial occlusions are permitted.

8. Pre-stroke (24 hours prior to stroke onset) independent functional status inactivities of daily living with modified Barthel Index (BI) ≥ 95. Patient must beliving without requiring nursing care.

9. Qualifying imaging performed less than 2 hours prior to randomization.

10. Consent process completed as per national laws and regulation and the applicableethics committee requirements.

Exclusion Criteria:

1. Treated with a tissue plasminogen activator (e.g., alteplase or tenecteplase) within 24 hours before randomization.

2. Determination by the treating physician, based on current treatment guidelines andmedical evidence, that treatment with a plasminogen activator is indicated.

3. Large core of established infarction defined as ASPECTS 0-4.

4. Absent or poor collateral circulation on qualifying imaging (e.g. collateral scoreof 0 or 1).

5. Any intracranial hemorrhage on the qualifying imaging.

6. Planned use of an endovascular device not having approval or clearance by therelevant regulatory authority.

7. Endovascular thrombectomy procedure is completed as defined by the presence of TICI 2c/3 reperfusion or completion of groin / arterial closure.

8. Clinical history, past imaging or clinical judgment suggesting that the intracranialocclusion is chronic or there is suspected intracranial dissection such that thereis a predicted lack of success with endovascular intervention.

9. Estimated or known weight > 120 kg (264 lbs).

10. Pregnancy/Lactation; female, with positive urine or serum beta human chorionicgonadotropin (β-hCG) test, or breastfeeding.

11. Known prior receipt of nerinetide for any reason, including prior enrolment in thisESCAPE-NEXT trial.

12. Severe known renal impairment defined as requiring renal replacement therapy (hemo-or peritoneal dialysis).

13. Severe or fatal comorbid illness that will prevent improvement or follow up.

14. Inability to complete follow-up treatment to Day 90.

15. Participation in another clinical trial investigating a drug, medical device, or amedical procedure in the 30 days preceding trial inclusion.