Evaluating the Safety, Pharmacokinetics and Efficacy of GS-5745 in Subjects With Moderate to Severe Ulcerative Colitis

The study will test the safety of the drug and a system has been built into the trial design
to ensure participant safety. Participants will be given different concentrations of the
drug (known as "cohorts") starting from a lower dose to a higher dose.

Single-Dose Treatment:

A thorough assessment of safety and tolerability will be performed before escalating to the
next higher dose. For example, the first 2 subjects will be dosed in a staggered fashion 24
hours apart. Provided that there are no significant safety signals up to 24 hours post-dose
for the first 2 subjects, the remaining 4 subjects will be dosed. A thorough assessment of
safety and tolerability (through day 14 post-dose) will be performed by the safety review
committee before escalating to the next higher dose. Subjects enrolled in a SAD cohort will
be eligible to participate in a MAD or adaptive MAD cohort if eligibility criteria are met.

Multiple-Dose Treatment:

This design follows the same set-up as the Single-Dose Treatment. Dosing will not commence
in the first MAD cohort until safety data from the second dose level SAD cohort has been
reviewed through Day 15. Successive MAD cohorts will only be dosed after safety data from
the previous, lower dose MAD cohort through Day 43 and the next higher dose SAD cohort
through Day 15, have been reviewed by the safety review committee. An additional Adaptive
MAD cohort will explore a subcutaneous dosing of GS-5745 150 mg prefilled syringe once a
week for 5 weeks.

Inclusion Criteria:

- Male or Female, 18 to 65 years of age

- Negative pregnancy test at screening

- Documented diagnosis of ulcerative colitis (UC) with a minimum disease extent of 15
cm from the anal verge

- Mayo Score of at least 3 for the SAD cohort and Mayo Score of at least 6 for the MAD
cohorts

- Hepatic panel (aspartate aminotransferase [AST], alanine aminotransferase [ALT],
total bilirubin, direct bilirubin, alkaline phosphatase, lactate dehydrogenase [LDH]
≤ 2 times the upper limit of the normal range [ULN])

- Serum creatinine ≤ 1.5 times the ULN

- Hemoglobin ≥ 10 g/dL (both males and females)

- Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (1,500 mm^3)

- Platelets ≥ 100 x 10^9/L

Exclusion Criteria:

- Pregnant or lactating females

- Exhibit severe UC/ clinically significant active infection

- Current use of oral corticosteroids at a dose equivalent to > 20 mg/day of prednisone

- Any dose adjustment in oral corticosteroids or oral immunosuppressants (6-MP,
Azathioprine), or oral 5-ASA compounds within 30 days of Baseline

- Use of rectal formulations of 5-ASA compounds or corticosteroids within 2 weeks prior
to randomization

- Crohn's disease or indeterminate colitis

- History of colectomy, partial colectomy, or dysplasia on biopsy

- Stool sample positive for Clostridium difficile (C. difficile) toxin, E. coli,
Salmonella, Shigella, Campylobacter or Yersinia

- Treatment with Infliximab, Adalimumab, Natalizumab, Golimumab, Vedolizumab or
Certolizumab within 8 weeks of randomization

- Any chronic medical condition (including, but not limited to, cardiac or pulmonary
disease) that, in the opinion of the Investigator, would make the individual
unsuitable for the study or would prevent compliance with the study protocol