Treatment of Acute Ischemic Stroke (ReMEDy2 Trial)

Inclusion Criteria:

1. Participant is between 18 and 90 years of age inclusive.

2. Participant weight is 40 kg to 166 kg inclusive.

3. Participant to be randomized and treatment initiated within 24 hours of last knownnormal/AIS stroke onset.

4. Participant has NIHSS ≥5 and ≤15 at approximately the time of randomization. Thiscriterion also applies to participants who meet the following conditions:

• The participant initially presents with an NIHSS score below 5 but clinicallyworsens, including cases of progressing stroke / stroke-in-evolution, resultingin a subsequent persistent NIHSS score of ≥5 and ≤15; and

• Participant meets all other inclusion and exclusion criteria, including repeatbrain imaging to rule out hemorrhagic transformation.

5. Participant had a pre-morbid mRS score of 0 to 1 (mRS score prior to AIS) as statedby participant or participant's representative.

6. If participant has received fibrinolytic treatment for AIS within 4.5 hours of lastknow normal/AIS stoke onset and at least 6 hours after completing fibrinolytictreatment, and the participant meets all of the following criteria:

• Participant's initial NIHSS score prior to fibrinolytics was ≤15; and

• At least six hours after fibrinolytics, the participant has NIHSS score of ≥5and ≤15 with a persistent deficit; and

• The participant's NIHSS score showed less than a 4-point improvement, orworsened, after receiving fibrinolytics; and

• Participant meets all other inclusion and exclusion criteria including repeatbrain imaging to rule out hemorrhagic transformation.

7. Participant and/or legally authorized representative is able to provide informedconsent.

8. Participant is willing and able to comply with the study protocol, in theInvestigator's judgment.

Exclusion Criteria:

1. At screening, or with repeat imaging (see Inclusion 4 and 6), participant hasimaging confirmed hemorrhage stroke.

2. Participant has image findings with symptomatic large vessel occlusion at one ormore of the following locations: Intracranial carotid I/T/L or M1 segment MCA,vertebral or basilar artery (BA).

3. Participant has large core of established infarction defined as ASPECTS 0-5.

4. Participant has or will receive MT for their current AIS.

5. Participant has suspected or confirmed extracranial arterial dissection.

6. Participant has imaging findings and/or symptoms consistent with a brain stem orcerebellar stroke. Posterior cerebral artery strokes without any associated brainstem or cerebellar involvement are allowable.

7. Participant has any recorded SBP <100 mmHg or MAP <65 mmHg; MAP = DBP + [1/3 (SBP -DBP)] (measured with noninvasive BP cuff type monitor) after stroke symptom onsetand prior to randomization.

8. Participant is currently prescribed angiotensin-converting enzyme inhibitor (ACEi)and is unable or unwilling to convert to another antihypertensive pharmacologicaltreatment through Day 29 ±1 day (8 days after last treatment).

9. Participant is currently prescribed an ACEi, and the last dose of the ACE inhibitormedication is reported to have been taken < 24 hours before start of IV study druginfusion as stated by participant or participant's representative.

10. Participant has a history of clinically significant allergic reactions such asangioedema or anaphylaxis requiring hospitalization.

11. Participant has a diagnosis or suspected diagnosis of hereditary angioedema (HAE) oris taking or prescribed medications commonly used as prophylaxis/treatment of HAE,such as C1-esterase inhibitors (Cinryze, Berinert, Ruconest, Haegarda), Danazol,kallikrein inhibitors (Ecallantide, Berotralstat, Lanadelumab), Bradykinin B2Receptor Antagonists (Icatibant), or other medication designed to influence thekallikrein-kinin system.

12. Life expectancy estimated at ≤1 year prior to enrollment.

13. Participant has clinical evidence of an active infection at the time of enrollmentrequiring parenteral treatment or hospitalization to monitor or manage theinfection. NOTE: Treatment of uncomplicated infections with oral antibiotics would not be anexclusion (for example, the treatment of uncomplicated urinary tract infections orsinus infections with oral antibiotics would not be exclusionary).

14. Participant has known alpha 1-antitrypsin deficiency (α1-antitrypsin deficiency).

15. Participant is pregnant or nursing. NOTE: Participants who agree to stop nursing maybe considered for inclusion at the discretion of the Investigator.

16. Participants of child-bearing potential must agree to use medically acceptablecontraceptive measures to prevent pregnancy. All participants of childbearingpotential (defined as sexually mature participants who have had menses within thepreceding 24 months and have not undergone permanent sterilization methods such ashysterectomy, bilateral oophorectomy, bilateral salpingectomy, etc.) must have anegative serum pregnancy test performed locally at screening. Participants ofchildbearing potential must agree not to attempt to become pregnant or undergo invitro fertilization. If participating in sexual activity that could lead topregnancy, participants must use 2 reliable methods (1 per partner is acceptable) ofcontraception simultaneously while receiving protocol-specified medication andduring the study follow-up period. Participants participating in sexual activity must agree to use, or for theirpartner to use highly effective birth control methods (those with a failure rate ofless than 1% per year when used consistently and correctly) until they havecompleted the study (after the Day 90 visit). Such methods include:

• Combined (estrogen and progesterone containing) hormonal oral, intravaginal, ortransdermal contraception associated with the inhibition of ovulation

• Progesterone-only oral, injectable, or implantable hormonal contraceptionassociated with the inhibition of ovulation

• Intrauterine device (IUD)

• Intrauterine hormone-releasing system (IUS)

• Bilateral tubal occlusion

• Vasectomized partner

• Sexual abstinence Participants who are not of reproductive potential (who havebeen postmenopausal for more than 24 consecutive months or have undergonehysterectomy, bilateral oophorectomy, bilateral salpingectomy, etc.) are notrequired to use contraception. Participants are prohibited from sperm donation. NOTE: A negative serum pregnancytest will be documented during screening if a participant is of child-bearingpotential.

17. Participant is currently participating in or has participated in a study using aninvestigational device or drug or received an investigational drug orinvestigational use of a licensed drug within 30 days prior to screening.

18. Participant does not have sufficient venous access for infusion of study treatmentor blood sampling.

19. Participant is unable or unwilling to comply with protocol requirements, includingassessments, tests, and follow-up visits.

20. Participant has any other medical condition which in the opinion of the Investigatorwill make participation medically unsafe or interfere with the study results.