Safety and Pharmacokinetics of Single Oral Doses of MBX-400 in Healthy Volunteers

Cytomegalovirus (CMV; herpesvirus 5), a member of the betaherpesvirus subgroup, occurs as a
benign infection in the majority of humans, with a 90% prevalence in the adult population1.
However, CMV infection continues to be a major cause of morbidity and mortality in
immunosuppressed patients, particularly recipients of solid organ or bone marrow
transplants. CMV is also known for its association with severe blinding retinitis,
pneumonia and gastrointestinal inflammation in AIDS patients. However, with the successful
introduction of HAART (highly active anti-retroviral therapy), the problem of CMV infection
in AIDS patients has decreased substantially. CMV remains the most important cause of
congenital viral infection in the United States, and CMV infection of neonates is associated
with deafness, mental retardation and mortality. In addition, CMV is a suspected pathogenic
agent in cardiovascular disease and can persist in large-vessel endothelial cells and infect
all cell types involved in cardiovascular lesions. CMV has been implicated in the
restenosis of diseased coronary arteries following angioplasty and has been associated with
myocarditis. In severely immunocompromised patients with CMV infection, prolonged antiviral
therapy is often necessary, which increases the risk of resistant viruses. Currently
available therapy has limitations that preclude their long-term use including toxicity, poor
oral bioavailability and the development of drug-resistant strains. MBX-400 is a nucleoside
analog that is structurally related to ganciclovir and acyclovir and is being developed for
the possible use in the prevention and/or treatment of CMV. MBX-400, has been shown to be a
potent inhibitor of viral DNA synthesis and therefore may be useful in treating and/or
preventing CMV infection.

Inclusion Criteria:

1. Male or female 18 to 65 years of age

2. Females must be surgically-sterilized or post-menopausal (defined as at least 1 year
since last menses with follicle stimulating hormone (FSH) level indicating subject is
post-menopausal)

3. Males must have undergone vasectomy

4. Able to understand study requirements, agrees to participate in the study and willing
and able to provide informed consent (using an informed consent form in a language in
which the subject is fluent)

5. Willing and able to stay in a clinical facility for up to 7 days

6. BMI of 18 to 32 kg/m2

7. Non-smoker or former smoker or user of nicotine-containing products (defined as
someone who smoked or used nicotine-products one or more times a week for at least
one month) who has not smoked for at least 3 months and has not used
nicotine-containing products for at least 1 month and is willing to abstain from
nicotine-containing products during the study

8. Has adequate venous access

9. Willing to abstain from alcohol and illicit drugs during the study

Exclusion Criteria:

1. Participation in another clinical trial within 3 months of screening

2. Unwilling to comply with study procedures or cooperate with study personnel.

3. Donated blood or had significant blood loss (greater than 1 unit) within 3 months of
screening

4. History of any of the following

- Human immunodeficiency virus (HIV), cytomegalovirus (CMV), hepatitis B or
hepatitis C infection

- Alcohol or drug abuse

- Anemia or bleeding disorders

- Gastrointestinal disorders

- Chronic illness

- Regular medication use (prescription, over-the-counter or herbal; defined as
more than once per week; except multivitamins) or use of medication (except
multivitamins) within 1 week of screening.

- Recent illness requiring treatment within 1 month of screening

- History of renal failure or renal insufficiency

5. Clinically significant abnormal electrocardiogram (e.g., abnormal rhythm, abnormal
intervals)

6. Clinically significant results of hematology, chemistry, coagulation studies or
urinalysis, including, but not limited to the following:

- White blood cell count, red blood cell count or platelet count less than the
lower limit of normal or greater than 1.5 times the upper limit of normal

- Hemoglobin or hematocrit less than the lower limit of normal or greater than the
upper limit of normal

- Alanine aminotransferase and aspartate aminotransferase greater than the upper
limit of normal

- Prothrombin, partial thromboplastin time or international normalized ratio
greater than 1.5 times the upper limit of normal

- Abnormal electrolyte values (i.e., sodium, potassium, carbon
dioxide/bicarbonate, chloride and/or calcium outside of the reference range)

- Urinalysis showing presence of red blood cells, protein or microalbumin

- Cotinine level indicative of nicotine use

- Positive test for any drug of abuse on urine drug screen

- Positive serum pregnancy test if female

- Positive ethanol test

7. Clinically significant vital signs

- Temperature above 100.0 °F

- Heart rate < 45 or > 100 beats per minute

- Respiratory rate < 12 or > 20 breaths per minute

- Systolic blood pressure < 100 or > 140 mm Hg OR diastolic blood pressure < 60 or
> 90 mm Hg

8. Known hypersensitivity to any ingredients in the MBX-400 capsules or Placebo capsules
(e.g., MBX-400, microcrystalline cellulose, gelatin, titanium dioxide).

9. Scheduled for surgical procedure during the study

10. Investigator deems that subject has a condition that warrants exclusion from or is
not suitable for the study