A PHASE II OPEN LABEL EXTENSION STUDY TO EVALUATE THE LONG TERM SAFETY AND TOLERABILITY OF UTTR1147A IN PATIENTS WITH MODERATE TO SEVERE ULCERATIVE COLITIS OR CROHN'S DISEASE

While effective therapeutic options, including anti-integrin agents and TNF
inhibitors, are available to reduce the acute symptomatic flares in disease
activity in patients with moderate to severe IBD, no currently available
therapy achieves sustained remission in more than 10%-30% of patients with
chronic IBD. Furthermore, anti integrin agents and TNF inhibitors are
associated with severe adverse events, including hypersensitivity reactions and
increased risk of infections (including serious infections such as
tuberculosis). Consequently, patients and physicians must carefully weigh the
benefit-risk ratio both before starting and while managing long-term treatment
with anti-integrin agents or TNF inhibitors.

IL-22 stimulates mucin and anti-microbial peptide production in the intestine,
which can modulate bacterial growth and protect the intestinal epithelium.
Changes in bacterial flora have been associated with a variety of
immunologically mediated diseases and, along with altered epithelial barrier
function, are thought to be key drivers in the inflammatory process of IBD.
UTTR1147A, an IL-22 fusion protein, is a novel therapeutic agent being
developed to promote mucosal healing and achieve sustained clinical remission
while potentially allowing reduction or elimination of the immunosuppression
associated with current therapies for IBD.

The safety profile of UTTR1147A, as demonstrated in the Phase I studies,
supports further investigation of UTTR1147A in the induction and maintenance of
clinical remission for patients who have failed conventional therapy. The
safety risks identified to date for UTTR1147A from the Phase I studies have
been well characterized in HVs and consist of dermatologic adverse events that
have been readily monitored, manageable, and reversible. As UTTR1147A is an
investigational medicinal product with limited Phase I patient data, the full
safety profile will be further characterized as Phase I and II clinical
development progresses.

Safety objective: To evaluate the safety and tolerability of UTTR1147A

Exploratory Efficacy Objective: To evaluate the efficacy of UTTR1147A

Exploratory Pharmacokinetic Objective: To evaluate potential relationships
between long-term drug exposure and the safety and efficacy of UTTR1147A

Exploratory Immunogenicity Objective: To evaluate the immune response to
UTTR1147A

Exploratory Biomarker Objective: To identify biomarkers that can increase the
knowledge and understanding of disease biology

Open-label extension study

Treatment with UTTR1147A will be determined on the basis of the patient's
disease status. Upon entry into the extension study, patients will receive
UTTR1147A 60 µg/kg IV Q4W or undergo observation, depending on their disease
status at the time of their last endoscopy in the parent study.

Side effects associated with UTTR1147A (in previous clinical studies these side
effects have not been serious and have been fully reversible):

Common (occurred in more than 10% of 44 healthy volunteers):
* Reddening of skin
* Dry/scaly skin
* Dry lips
* Increase in substance produced by the liver that increases in the presence of
inflammation in the body (C-reactive protein), but without signs or symptoms to
suggest inflammation (e.g., fevers, chills, or fatigue)

Less common (occurred in 1%-10% of 44 healthy volunteers)
* Itchy skin
* Painful skin
* Increase in protein that helps in the formation of blood clots, but without
signs or symptoms of blood clots

The following are side effects that may be associated with UTTR1147A:
* Risk of growth of existing tumors (such as skin tumors or other tumors that
you may already have in your body), because UTTR1147A may stimulate growth of
certain tumors. To date, UTTR1147A has not increased the growth of any cancers
in humans.
* Risk of having an infusion reaction or allergic reaction to UTTR1147A.
Infusion reactions or allergic reactions may be mild, such as skin rash or
hives, or severe, such as breathing difficulties. A severe infusion reaction
or severe allergic reaction requires immediate medical treatment and could
result in permanent disability or death.
* Risk that the immune system might develop special antibodies to the drug or
to the body*s own IL-22. If this occurs, these antibodies could cause several
different effects, such as an allergic reaction to UTTR1147A or a change in
your body*s ability to respond to infections (including infections in your
digestive system that may or may not be due to your ulcerative colitis) that
could be long-lasting.

Possible Risks and Discomfort Associated With switching Treatment from
vedolizumab to UTTR1147A
If patient participated in the parent study GA39925, there is a possibility
that the treatment he/she receive will be switched from vedolizumab to
UTTR1147A. If this happens, the disease might worsen and he/she might require
rescue treatment. It is also possible that patient might develop special
antibodies against vedolizumab if the vedolizumab treatment is stopped.

Possible Risks and Discomfort Associated with Drawing Blood
During this study, small amounts of blood will be drawn from a vein and used
for tests that allow your study doctors to see how you are doing. Drawing
blood may cause pain where the needle is inserted, and there is a small risk of
bruising or infection at the place where the needle is inserted. Some people
experience dizziness, upset stomach, or fainting when their blood is drawn.

Flexible Sigmoidoscopy, ileocolononscopy, and colonoscopy
Patient may experience some discomfort during the examination. Rare
complications include bleeding (occurring less than 1%-2% of the time,
complications relating to sedation, such as low blood pressure or heart rhythm
problems (occurring less than 0.5% of the time), and bowel perforation
(occurring less than 1% of the time), which could require surgery or could even
be fatal.

Electrocardiogram
An ECG is painless. No electricity is sent through the body. In rare cases,
some people may develop a rash or irritation where the patches were placed.

Possible Risks and Discomfort Associated with Biopsies
Risks associated with a colon biopsy sample collection include bleeding and
infection. Rare complications include bowel perforation, which may require
urgent surgery. A skin biopsy may be collected if you experience a skin
reaction. Risks associated with skin biopsies include pain, redness, swelling,
excessive bleeding, bruising, or draining at the needle site, abnormal wound
healing, fever, infection, and allergic reaction to the medication used to numb
the skin over the biopsy site.