Safety and Efficacy Study of PTG-100 in the Treatment of Moderate to Severe Ulcerative Colitis

This is a Phase II multi-centre, double blind, randomised, placebo-controlled, clinical study
to evaluate the efficacy, safety, and tolerability of an oral peptide, PTG-100, administered
as capsules for 12 weeks in subjects with moderate to severe UC.

Following screening procedures and confirmation of subject eligibility, subjects will be
randomised 1:1:1:1 to one of three daily doses of PTG-100 (150, 300 or 900 mg) or placebo.
Stratification will be based on subjects' prior treatment with anti-TNF agents, with a
maximum of 50% of subjects with prior unsuccessful anti-TNF agent treatments. Subjects will
be treated with study drug for 12 weeks. Sigmoidoscopies will be performed at the Screening
Visit and on Week 12. A final Follow Up Visit will occur on Week 16, when subject has been
off study treatment for 4 weeks. Clinical, safety, pharmacokinetic (PK) and pharmacodynamic
(PD) parameters will be evaluated on an ongoing basis during the 16 week study.

Inclusion Criteria include:

- Male and female subjects age 18 to 80 years, inclusive

- Diagnosis of UC for at least 2 months prior to screening

- Moderate to severe active UC as defined by Mayo Score of 6 to 12 inclusive (range of
0-12) at baseline with endoscopy score of at least 2 (range 0-3)

- Subject must have had an inadequate response, loss of response to or intolerance to at
least of of the following medications: immunomodulators, TNF-alpha antagonists or
corticosteroids

- Subject is unlikely to conceive, as defined by one of the following: a) subject is
male, b) subject is surgically sterilized female, c) subject is post-menopausal female
>= 45 years of age with clinical documentation of menopause, or d) subject is woman of
child bearing potential (WOCBP) and agrees to abstain from heterosexual activity, use
adequate hormonal contraception or use double barrier contraception.

- For WOCBP, a negative pregnancy test at screening and within 24 hours of first dose of
study medication

Exclusion Criteria include:

- Subject has Crohn's Disease (CD), indeterminate colitis (IC) or presence or history of
fistula with CD

- History of toxic megacolon, abdominal abscess, symptomatic colonic stricture or stoma;
history or is at imminent risk of colectomy

- History or current evidence of colonic dysplasia or adenomatous colonic polyps

- Current bacterial or parasitic pathogenic enteric infection, including Clostridium
difficile, infection with hepatitis B or C virus, infection with human
immunodeficiency virus, infection requiring hospitalisation or intravenous
antimicrobial therapy, or opportunistic infection within 6 months, any infection
requiring antimicrobial therapy within 2 weeks, history of more than one episode of
herpes zoster or any episode of disseminated zoster

- Live virus vaccination within one month prior to screening

- Subject has a concurrent clinically significant, unstable, or uncontrolled
cardiovascular, pulmonary, hepatic, renal, gastrointestinal, genitourinary,
hematological, coagulation, immunological, endocrine/metabolic, or other medical
disorder that, in the opinion of the investigator, might confound the study results or
poses additional risk to the subject

- Known primary or secondary immunodeficiency

- History of myocardial infarction, unstable angina, transient ischaemic attack,
decompensated heart failure requiring hospitalisation, congestive heart failure (NYHA
Class 3 or 4), uncontrolled arrhythmias, cardiac revascularisation, stroke,
uncontrolled hypertension, or uncontrolled diabetes within 6 months of screening

- Clinically meaningful laboratory abnormalities at screening

- Pregnant or lactating females

- Any surgical procedure requiring general anaesthesia within one month prior to
screening, or planned elective surgery during the study

- History of malignant neoplasms or carcinoma in situ within 5 years prior to screening

- History of any major neurological disorders, as judged by the Investigator, or
positive progressive multifocal leukoencephalopathy (PML) subjective symptom checklist

- Current or recent history of alcohol dependence or illicit drug use within 1 year
prior to screening.

- Subject is mentally or legally incapacitated at the time of screening visit or has a
history of clinically significant psychiatric disorders that would impact the
subject's ability to participate in the trial according to the investigator

- Unable to attend study visits or comply with procedures

- Concurrent participation in any other interventional study.