A Phase 3 Study of LJPC-501 in Patients With Catecholamine-Resistant Hypotension

Catecholamine-resistant hypotension (CRH) is an often fatal condition resulting from an
underlying cause such as septic shock, inflammation due to trauma, or severe drug reactions.
When these conditions occur, most patients will respond to either volume expansion or
vasopressor treatment. However, some patients will require excessive doses of vasopressors
and will be deemed to be resistant.

Angiotensin II is a peptide hormone naturally produced by the body that regulates blood
pressure via vasoconstriction and sodium reabsorption. LJPC-501 (angiotensin II) is being
developed for the treatment of patients with catecholamine-resistant hypotension (CRH).

This is a multi-site, randomized, double-blind, placebo-controlled study. Adult patients with
CRH, who are hospitalized in an ICU setting, may be eligible to participate. Approximately
315 patients will be enrolled.

Inclusion Criteria:

1. Adult patients ≥ 18 years of age with CRH, defined as those who require a total sum
catecholamine dose of > 0.2 mcg/kg/min for a minimum of 6 hours and a maximum of 48
hours, to maintain a MAP between 55-70 mmHg.

2. Patients are required to have central venous access and an arterial line present, and
these are expected to remain present for at least the initial 48 hours of study.

3. Patients are required to have an indwelling urinary catheter present, and it is
expected to remain present for at least the initial 48 hours of study.

4. Patients must have received at least 25 mL/kg of crystalloid or colloid equivalent
over the previous 24-hour period, and be adequately volume resuscitated in the opinion
of the treating investigator.

5. Patients must have clinical features of high-output shock by meeting one of the
following criteria.

1. Central venous oxygen saturation (ScvO2) > 70% (either by oximetry catheter or by
central venous blood gas) and central venous pressure (CVP) > 8 mmHg.

OR

2. Cardiac Index (CI) > 2.3 L/min/1.73 m2. Patient must meet 5a or 5b to be
eligible.

6. Patient or legal surrogate is willing and able to provide written informed consent and
comply with all protocol requirements.

Exclusion Criteria:

1. Patients who are < 18 years of age.

2. Any patient with burns covering > 20% of total body surface area (TBSA).

3. Patients with a Cardiovascular (CV) SOFA score ≤ 3.

4. Patients diagnosed with acute occlusive coronary syndrome requiring intervention.

5. Patients on veno-arterial (VA) ECMO.

6. Patients who have been on ECMO for less than 12 hours.

7. Patients in liver failure with a Model for End-Stage Liver Disease (MELD) score of ≥
30.

8. Patients with a history of asthma or who are currently experiencing bronchospasm
requiring the use of inhaled bronchodilators, if not mechanically ventilated.

9. Patients with acute mesenteric ischemia or a history of mesenteric ischemic.

10. Patients with a history of, presence of, or highly-suspected of having an aortic
dissection or abdominal aortic aneurysm.

11. Patients requiring more than 500 mg daily of hydrocortisone or equivalent
glucocorticoid medication as a standing dose.

12. Patients with Raynaud's phenomenon, systemic sclerosis or vasospastic disease.

13. Patients with an expected lifespan of < 12 hours.

14. Patients with active bleeding AND an anticipated need (within 48 hours of initiation
of the study) for transfusion of > 4 units of packed red blood cells.

15. Patients with active bleeding AND hemoglobin < 7g/dL or any other condition that would
contraindicate serial blood sampling.

16. Patients with an absolute neutrophil count (ANC) of < 1000 cells/mm3.

17. Patients with a known allergy to mannitol.

18. Patients who are current participating in another interventional clinical trial.

19. Patients who are known to be pregnant at the time of Screening.