A Study to Evaluate Efficacy and Safety of QPI-1002 for Prevention of Acute Kidney Injury Following Cardiac Surgery

This is a randomized, double-blind, placebo-controlled, Phase 2 trial to evaluate QPI-1002
versus placebo for the prevention of AKI in subjects who are at high risk for AKI following
cardiac surgery.

Inclusion Criteria:

- Have the ability to understand the requirements of the study, are able to provide
written informed consent and are willing and able to comply with the requirements of
the study

- Male or female, age ≥ 45 years old.

- Have stable renal function per Investigator assessment and no known increase in serum
creatinine of ≥ 0.3 mg/dL during preceding 4 weeks.

- Scheduled to undergo non-emergent open chest cavity cardiovascular surgeries,
including use of coronary pulmonary bypass (CPB) and no CPB:

- Combined coronary artery bypass grafting (CABG) surgery and surgery of one or
more cardiac valve (valve(s) surgery) and at least 1 AKI Risk Factor;

- Surgery of more than one cardiac valve (valve surgery) and at least 1 AKI Risk
Factor;

- Surgery of the aortic root or ascending part of the aorta, or in combination with
the aortic valve, and at least 1 AKI Risk Factor; circulatory arrest is not
excluded;

- Aortic root or ascending part of the aorta, combined with CABG and/or valve(s)
surgery and at least 1 AKI Risk Factor; circulatory arrest is not excluded;

- If only CABG or single valve surgery, subjects are required to have at least 2
AKI Risk Factors:

AKI Risk Factors:

- Age ≥ 70 years

- eGFR ≤ 60 ml/min/1.73m2 by CKD-EPI formula at Screening.

- Diabetes (Type 1 or 2), requiring at least 1 oral hypoglycemic agent or insulin

- Proteinuria ≥ 0.3g/d, spot UPCR ≥ 0.3g/gm or urine dip stick ≥ +2

- History of congestive heart failure requiring hospitalization

Exclusion Criteria:

- Have an eGFR ≤ 20 mL/min/1.73 m2

- Subjects with an eGFR ≤ 60 mL/min/1.73 m2 requiring intravascular iodinated contrast
within 48 hours of the day of surgery. However, subjects may be included if the post
contrast increase in serum creatinine is < 0.3 mg/dl in at least 2 serum creatinine
evaluations performed not less than 36 hours apart.

- Have a history of any organ or cellular transplant which requires active
immunosuppressive treatment which can interfere with kidney function

- Emergent surgeries, including aortic dissection, and major congenital heart defects

- Scheduled to undergo transcatheter aortic valve implantation (TAVI) or transcatheter
aortic valve replacement (TAVR) or single vessel, mid-CAB off-pump surgeries or left
ventricular assist device (LVAD) implantation

- Have participated in an investigational drug study in the last 30 days

- Have a known allergy to or had participated in a prior study with siRNA

- Have a history of human immunodeficiency virus (HIV) infection

- Have known active Hepatitis B (HBV) (Note: Subjects with a serological profile
suggestive of clearance, or prior antiviral treatment of HBV infection may be
enrolled)

- Are HCV-positive (detectable HCV RNA) (Note: Subjects at least 24 weeks from
completion of treatment with an antiviral regimen and who remain free of HCV as
determined by HCV RNA testing may be enrolled.)

- Have had cardiogenic shock or hemodynamic instability within the 24 hours prior to
surgery, requiring inotropes or vasopressors or other mechanical devices such as
intra-aortic balloon counter-pulsation (IABP)

- Have required any of the following within a week prior to cardiac surgery:
defibrillator or permanent pacemaker, mechanical ventilation, IABP, left ventricular
assist device (LVAD), other forms of mechanical circulatory support (MCS) (Note: The
prophylactic insertion of an IABP preoperatively for reasons not related to existing
LV pump function is not exclusionary).

- Have required cardiopulmonary resuscitation within 14 days prior to cardiac surgery

- Have ongoing sepsis or history of sepsis within the past 2 weeks or untreated
diagnosed infection prior to Screening visit. Sepsis is defined as presence of a
confirmed pathogen, along with fever or hypothermia, and hypoperfusion or hypotension

- Have total bilirubin or alanine aminotransferase (ALT) or aspartate aminotransferase
(AST) > 2 times the upper limit of normal (ULN) at time of screening

- Have Child Pugh Class A liver disease with ALT/AST above the upper limit of normal or
Class B or higher. (This criterion is only applicable in a patient population with
underlying chronic liver disease, i.e., cirrhosis.)