Phase 3 Safety and Efficacy Study of ART-123 in Subjects With Severe Sepsis and Coagulopathy

Study is to evaluate if ART-123 given to patients who have severe sepsis complicated by at
least one organ dysfunction and coagulopathy can decrease mortality.

Inclusion Criteria:

- Subject must be receiving treatment in an ICU, or in an acute care setting (e.g., ER,
RR)

- Clinical objective evidence of bacterial infection and a known site of infection.

- Cardiovascular dysfunction or Respiratory Failure due to sepsis.

- Coagulopathy characterized by an INR >1.40 without other known causes.

Exclusion Criteria:

- Subject or Authorized Representative is unable to provide informed consent.

- Subject is pregnant or breastfeeding or intends to get pregnant within 28 days of
enrolling into the study.

- Subject is of childbearing potential and does not have a negative pregnancy test.

- Subject is < 18 years of age.

- Subject has a known allergy to ART-123 or any components of the drug product.

- Subject is unwilling to allow transfusion of blood or blood products.

- Subject has an advance directive to withhold life-sustaining treatment.

- Subject has had previous treatment with ART-123.

- Body weight ≥ 175 kg.

- Platelets < 30,000/ mm3 for any reason, PT prolongation or thrombocytopenia that is
not due to sepsis.

- Any surgery that is potentially hemorrhagic (e.g. intra-thoracic, intra-abdominal or
non-traumatic orthopedic surgery of the femur or pelvis) that is completed within 12
hours prior to first dose of study drug, or ongoing impairment of hemostasis as a
result of one of these procedures

- History of head trauma, spinal trauma, or other acute trauma with an increased risk of
bleeding within 3 months prior to consent.

- Cerebral Vascular Accident (CVA) within 3 months prior to consent.

- Any history of intracerebral arteriovenous malformation (AVM), cerebral aneurysm, or
mass lesions of the central nervous system.

- History of congenital bleeding diathesesor anatomical anomaly that predisposes to
hemorrhage (e.g. hemophilia, hereditary hemorrhagic telangiectasia).

- Significant gastrointestinal bleeding within 6 weeks prior to consent.

- Subject is diagnosed with a known medical condition associated with a hypercoagulable
state.

- Child-Pugh score of 10-15 (Class C)

- Portosystemic hypertension or known history of bleeding esophageal varices.

- History of solid organ, allogeneic bone marrow, or stem cell transplantation within
the 6 months prior to consent.

- Acute pancreatitis where infection has not been documented by a positive blood or
abdominal fluid culture or gram stain consistent with bacterial infection.

- Subjects with renal dysfunction defined as (a) Chronic renal failure requiring renal
replacement therapy (RRT), or (b) Acute renal failure with onset of oliguria (urine
output < 0.3 ml/kg/hr) > 48 hours prior to first dose of study drug whether receiving
RRT or not

- Use of anticoagulants, antiplatelet agents, antithrombotics and thrombolytics within
the 72 hours prior to first does of study drug.

- Life expectancy < 90 days.

- Current use of any chemotherapy agent likely to cause myeloablation (severe or
complete depletion of bone marrow).

- Participation in another research study involving an investigational agent within 30
days prior to consent or projected study participation during the 28 days post study
randomization.

- Confirmed or suspected endocarditis