The Effect Of NS-0200 Versus Placebo On Hepatic Fat Content In Patients With Non Alcoholic Fatty Liver Disease

This is a randomized, 16-week, placebo-controlled, double-blind study to evaluate the effect
of two fixed-dose combinations of leucine, metformin and sildenafil, NS-0200 compared to
placebo, on the reduction of liver fat in patients diagnosed with non-alcoholic fatty liver
disease (NAFLD). Subjects meeting all the inclusion criteria and no exclusion criteria will
be randomized to one of three study arms.

The primary objective of this study is to evaluate the change in hepatic fat content assessed
by proton-density-fat-fraction (PDFF) employing magnetic resonance imaging (MRI) in subjects
from : Screening/Visit 2 (Day-7/Week-1) to Study Termination/Visit 8 (Day 112/Week 16)
receiving two fixed-dose combinations of leucine, metformin and sildenafil compared to
placebo. Secondary objectives will also assess changes in serum alanine aminotransferase
(ALT) activity, change in circulating cytokeratin 18, a surrogate marker of
necro-inflammation, change in HbA1c, change in fasting glucose, insulin and insulin
sensitivity, change in blood lipids such as cholesterol, LDL, HDL, triglycerides, and changes
in in C-reactive protein. In addition this study will evaluate the safety and tolerability of
NS-0200.

Patients will have two screening visits, the first to determine their eligibility based on
lab tests and the second based on the percentage of hepatic fat assessed by MRI imaging. Once
qualified, patients will be randomly assigned to either one of the treatment groups or the
placebo control group and monitored for a total of 16 weeks. Patients will return to the
clinic each month for lab tests, and routine examinations. At the conclusion of the treatment
period patients will again undergo an MRI scan to examine the percentage of hepatic fat.

Inclusion Criteria:

1. Age 18-75 at study entry.

2. Is male, or female and, if female, meets all of the following criteria:

1. Not breastfeeding

2. Post-menopausal or negative serum pregnancy test result (human chorionic
gonadotropin, beta subunit [β-hCG]) at Screening /Visit 1 (Day-14/Week-2) (not
required for hysterectomized females)

3. If of childbearing potential (including peri-menopausal women who have had a
menstrual period within one year) must practice and be willing to continue to
practice appropriate birth control (defined as a method which results in a low
failure rate, i.e., less than 1% per year, when used consistently and correctly,
such as double barrier methods [male condom with spermicide, with or without
cervical cap or diaphragm], implants, injectables, oral contraceptives [must have
been using for at least the last 3 months], some intrauterine contraceptive
devices, tubal ligation, or in an established relationship with a vasectomized
partner) during the entire duration of the study.

3. Has been diagnosed with NAFLD via CT (positive for excess liver fat), ultrasound
(positive for excess liver fat), MRI (PDFF showing > 15% liver fat) or via biopsy
(showing >33% fat) within the past six months. If diagnosis was between 3 and 6 months
prior to Screening, an ultrasound (positive for excess liver fat) is required prior to
the Screening /Visit 1 (Day-14/Week-2) MRI.

4. Has liver fat (as measured by PDFF via MRI) greater than 15% at Screening/Visit 2
(Day-7/Week-1)

5. Has had ALT levels >30 U/L for men, >19 U/L for women measured within 8 weeks of
enrollment

6. Has an HbA1c equal to or less than 9% at Screening /Visit 1 (Day-14/Week-2)

7. Has a BMI between 25kg/m2 and 40 kg/m2

8. Otherwise stable health for preceding twelve weeks

9. Clinical laboratory tests (hematology, clinical chemistry, and urinalysis) either
normal or with abnormalities consistent with NAFLD.

10. Is able to read, understand, and sign the informed consent forms (ICF) and, when
applicable, an authorization to use and disclose protected health information form
(consistent with Health Insurance Portability and Accountability Act of 1996 [HIPAA]
legislation), communicate with the investigator, and understand and comply with
protocol requirements.

Exclusion Criteria:

1. Clinically significant renal dysfunction defined as a serum creatinine concentration
>1.4 mg/dL (females) or >1.6 mg/dL (males) or a blood urea nitrogen concentration >45
mg/dL at screening.

2. Use of any of the following medications:

1. Metformin

2. Combination drugs that include Metformin

3. Sildenafil

4. Tadalafil

5. Vardenafil

6. Pioglitazone

7. Rosiglitazone

8. Short acting insulins

9. An alpha blocker

10. Oral nitrates

11. Medications associated with increased hepatic steatosis

12. Insulins

13. OCT2/MATE inhibitors (e.g. cimetidine, quinidine, and pyrimethamine)

- Methotrexate

- Tamoxifen

- Corticosteroids (Nasal steroids are allowed if the subject has been on a
stable dose for the past 12 weeks and the dose employed does not exceed the
maximal recommended dose.)

- Estrogens

- Amiodarone

- Valproic acid

- Coumadin

- Isoniazide

- Nucleoside analogues used for the treatment of HIV infections

14. Any dietary supplement other than multi-vitamins

3. Evidence of significant alcohol consumption (defined as >7 drinks/week for females and
>14 drinks/week for males) within 6 months prior to randomization or presence or
suspicion of other forms of chronic liver disease (e.g., cirrhosis, autoimmune
hepatitis (>1:160 ANA), Wilson's disease, Hemochromatosis (Ferritin >1000 ug/L and
percent iron saturation >45%), hepatitis A, B or C)

4. Has a clinically significant medical condition that could potentially affect study
participation and/or personal well-being, as judged by the investigator, including but
not limited to the following conditions:

1. Unable to undergo MRI or contraindications for MRI procedure

2. History of cardio- or cerebro-vascular disease event within the previous 6 months

3. Requires anti-coagulation therapy

4. Gastrointestinal disorders including, but not limited to, the following:
pancreatitis, inflammatory bowel disease, or other diseases associated with
malabsorption or persistent abdominal discomfort

5. Endocrine disorders other than type 2 diabetes and hypothyroidism on stable
replacement therapy

6. Chronic infection (e.g., tuberculosis, human immunodeficiency virus infection,
hepatitis A virus, hepatitis B virus, or hepatitis C virus)

7. Neurological or psychiatric diseases that preclude valid execution of informed
consent or may interfere with the subject's compliance with study procedures
(e.g., major depressive disorder within the last 2 years, a history of suicidal
behavior in the last 3 months)

8. History of other psychiatric disorders including schizophrenia and bipolar
disorder)

5. Participation in a weight loss program within the past 3 months.

6. Weight change ≥5% during the past month.

7. History of substance abuse (including alcohol abuse as defined above) in the past 3
months or a positive screen for drugs of abuse or alcohol at screening.

8. Has received any investigational drug within 3 months of Screening.

9. Has donated blood within 3 months before Screening or is planning to donate blood
during the study.

10. Has had a serious infection, such as pneumonia in the previous 12 weeks

11. Has known allergies or hypersensitivity to metformin, sildenafil or leucine

12. Is an immediate family member (spouse, parent, child, or sibling; biological or
legally adopted) of personnel directly affiliated with the study at the clinical study
site, or NuSirt Biopharma.

13. Is employed by NuSirt Biopharma (defined as an employee, temporary contract worker, or
designee responsible for the conduct of the study).