Safety Evaluation of 3K3A-APC in Ischemic Stroke

This was a multicenter, prospective, randomized, controlled, double-blinded Phase 2 study
intended to evaluate the safety, PK and preliminary efficacy of 3K3A-APC following treatment
with tPA, mechanical thrombectomy or both in subjects with moderate to severe acute ischemic
stroke.

Approximately 115 subjects were to be randomized, which included the planned 88 subjects in
groups of 4 subjects to either 3K3A-APC or placebo (in a 3:1 ratio) and the additional
placebo subjects who were enrolled during safety review pauses. This study used a modified
version of the continual reassessment method (CRM) in order to establish a maximum tolerated
dose (MTD).

Eligible subjects received 3K3A-APC or placebo every 12 hours for up to 5 doses
(approximately 3 days), or until discharge from the hospital, whichever occurred first.
Subjects were monitored for safety evaluations through Day 7 (or discharge, if earlier) and
were expected to be seen on Day 7, 14, 30, and 90 for safety and outcome evaluations.

Inclusion Criteria:

- Acute ischemic stroke

- Able to receive IV tPA, mechanical thrombectomy or both

- National Institutes of Health Stroke Scale (NIHSS) score of ≥ 5

- Signed informed consent

- Mechanical thrombectomy subjects only: onset time to arterial puncture time < 6 hours

Exclusion Criteria:

- History of stroke or penetrating head injury within 90 days prior to enrollment

- History of previous or current diagnosis of intracranial hemorrhage that represents a
potential for re-hemorrhage if subjected to thrombolytic therapy or mechanical
thrombectomy

- Moyamoya disease, cerebral arterio-venous malformation (AVM), known unsecured aneurysm
requiring intervention during the acute study period

- Presence of other neurological or non-neurological co-morbidities that may lead,
independently of the current stroke, to further deterioration in the subject's
neurological status during the trial period

- Presence of premorbid neurological deficits and functional limitations assessed by a
retrospective Modified Rankin Scale (mRS) score of ≥ 2

- Mechanical thrombectomy subjects only: baseline non-contrast CT scan revealing a large
core occlusion as defined by local protocol

- Prolonged prothrombin time (PT) or activated partial thromboplastin time (aPTT)

- Severe hypertension or hypotension

- Glomerular filtration rate (GFR) <35 mL/min

- Blood glucose concentration < 50 mg/dL

- Prior exposure to any exogenous form of APC