Pharmacokinetics, Pharmacodynamics and Safety of Basis in Acute Kidney Injury Study

Acute kidney injury (AKI) is common, growing in incidence, and associated with significant
morbidity and mortality. Sirtuins are anti-aging enzymes that play a diverse role in cellular
energy metabolism and gene regulation. Mice deficient in SIRT1 are more susceptible to
developing AKI and sirtuin activation is a potential treatment for AKI.

This is a randomized, double-blind, placebo-controlled, stepwise study of escalating doses of
Basis (NR/pterostilbene) in patients with AKI. The study will potentially comprise up to four
Steps. The purpose of the stepwise approach is to identify the dose of Basis that achieves at
least a 50% and up to 100% increase in white blood cell (WBC) content of nicotinamide adenine
dinucleotide (NAD+) without side-effects.

During each Step, Basis (5 patients) or placebo (1 patient) will be given twice a day for 2
days. Patients will have frequent blood sampling performed for a 24 hour period following
dosing on Day 1 and then at 48 hr. The measurements in blood will include NR/pterostilbene
blood concentrations and NAD+ and NAAD (nicotinic acid adenine dinucleotide) concentrations
in WBCs.

Inclusion Criteria:

1. Male or female hospitalized patients, age ≥ 18 years.

2. Patients who have developed AKI (defined by an increase in serum creatinine by ≥0.3
mg/dL within 48 hours; or an increase in serum creatinine to ≥1.5 times baseline,
which is known or presumed to have occurred within the prior seven days).

3. Adequate hematological and liver function, as assessed by the following laboratory
requirements:

1. Hemoglobin ≥10.0 g/dL

2. Absolute neutrophil count (ANC) ≥1,500/mm3

3. Platelet count 100,000/mm3

4. Total bilirubin ≤1.5 x upper limit of normal (ULN).

5. ALT and AST ≤2.5 x ULN.

4. Able to provide written informed consent in compliance with the Human Investigation
Review Committee (IRB).

Exclusion Criteria:

1. Exposure to any investigational agent within 30 days prior to enrollment.

2. Known allergy to any of the study drugs or their excipients.

3. Currently pregnant (confirmed with a positive serum pregnancy test) or nursing.

4. Unstable or clinically significant concurrent medical condition, psychiatric illness
or social situation that would, in the opinion of the investigator, jeopardize the
safety of a subject and/or their compliance with the protocol.

5. Baseline CKD stage 4-5 (eGFR<30 mL/minute/1.73 m2 as determined using the Modification
of Diet in Renal Disease (MDRD) equation; in cases where the MDRD equation may not be
suitable, a 24 hour urine creatinine clearance test may be substituted), prior to
current hospitalization

6. Any malignancy with the exception of cervical carcinoma in situ,nonmelanoma skin
cancer, or superficial bladder tumors that have been successfully and curatively
treated with no evidence of recurrent or residual disease.