Efficacy and Safety of SANGUINATE™ for Reduction of Delayed Graft Function in Patients Receiving a Kidney Transplant

Phase 2: Sixty (60) adult subjects who will be recipients of a donation after brain death
(DBD) donor kidney and who meet all eligibility criteria will be randomized 1:1 within 48
hours prior to transplant surgery to receive: two infusions of SANGUINATE at a dose of 320
mg/kg or placebo on the day of surgery and approximately 24 hours after surgery. Patients
will be hospitalized for up to 5 days and the study duration will be 30 days. Results will
be used to inform the study design characteristics for Phase III, including sample size.

Phase III: The same inclusion/exclusion requirements, dosing schedule, hospitalization stay
and outpatient visits as in Phase II with additional visits scheduled at Day 90, Day 180 and
Day 365. Study duration will be 365 days.

Inclusion Criteria:

1. Able to understand and provide written informed consent.

2. Male or female subject at least 18 years of age.

3. Dialysis-dependent renal failure initiated at least 3 months prior to
transplantation.

4. Subject is to be the recipient of a first kidney transplant from a deceased donor
(brain death criteria).

5. Is able to receive intravenous infusions of study drug.

6. Anticipated donor organ cold ischemia time < 30 hours.

7. A calculated prediction of DGF risk of least 25%.

8. Females of childbearing potential must agree to use 2 forms of effective birth
control regimen (at least one-barrier method) during the initial 30-day study period.

9. Male subjects must agree to use condoms or other suitable means of pregnancy
prevention.

Exclusion Criteria:

1. Has received a blood transfusion of packed red blood cells (PRBC), other than with
leukocyte-poor blood, within the 90-day period prior to screening.

2. Recipient of a live donor kidney or a kidney from a donation after cardiac death
(DCD) donor.

3. Recipient of donor kidney preserved with normothermic machine perfusion.

4. Is scheduled to undergo multi-organ transplantation.

5. Has planned transplant of kidney(s) from a donor < 6 years of age.

6. Has planned transplant of kidneys that are implanted en bloc (dual kidney
transplant).

7. Has planned transplant of dual kidneys (from the same donor) transplanted not en
bloc.

8. Body Mass Index (BMI) > 38 kg/m2

9. Is scheduled for transplantation of a kidney from a donor who is known to have
received an investigational therapy (under another Investigational New Drug) for
ischemic/reperfusion injury immediately prior to organ recovery.

10. Is scheduled to receive an blood type-incompatible donor kidney.

11. Has undergone desensitization to remove antibodies prior to transplantation.

12. Total bilirubin > 1.5 mg per dL, transaminase more than twice the upper limit of
normal or evidence of hepatic insufficiency

13. Has participated in an investigational study within the last 30 days or received an
investigational product within 5 half-lives of the study drug administration,
whichever is longest. Potential subjects participating in a strictly observational
study or a study involving approved treatments should be discussed with the Medical
Monitor.

14. Has a history of human immunodeficiency virus (HIV)

15. History or presence of active substance abuse (illicit drugs or alcohol) in the
previous 6 months, as believed by the Investigator

16. Presence of ECG-based evidence of acute myocardial infarction, unstable angina,
decompensated heart failure, third degree heart block or cardiac arrhythmia
associated with hemodynamic instability

17. History or presence of any disease or psychiatric condition that in the
Investigator's assessment that would increase the risk to subjects associated with
study participation, drug administration or interpretation of results

18. History of biopsy-confirmed malignancy within 5 years of randomization, with the
exception of adequately treated basal cell or squamous cell carcinoma in situ skin
lesions, carcinoma of the cervix in situ, or early detected prostate cancer.

19. Female subject who is pregnant or breast feeding.