An Efficacy and Safety Study of Mongersen (GED-0301) in Subjects With Active Ulcerative Colitis

Eligible subjects will have the Baseline Visit (Week 0/ Visit 2) and receive the following
treatments:

- Induction Phase - GED-0301 160 mg once daily (QD) for 8 weeks;

- Extension Phase - GED-0301 160 mg on alternating dosing schedule (GED-0301 160 mg QD for
4 weeks, followed by 4 weeks without GED-0301 treatment) for an additional 44 weeks.
Subjects who do not achieve at least a 20% decrease in partial mayo score (PMS) from
baseline at Week 12 will be discontinued from the study.

Clinical, safety, and pharmacokinetic (PK) data will be evaluated on an ongoing basis,
however, if the response to treatment is lower than expected (eg, ≤2 subjects achieving
clinical remission based on modified Mayo score (MMS)) when 50% of the subjects complete Week
8, or discontinue before Week 8, the study team will review available data (clinical, safety,
and PK) to evaluate if the study conduct should be modified.

This evaluation will be based on clinical judgment and the following guidance

- Consider starting a new cohort of subjects using a QD dose up to 320 mg if there is
endoscopic or histologic evidence of proximal colon benefit but limited or no distal
colon drug exposure/efficacy. Also, there is evidence of potential overall efficacy
(total Mayo score (TMS), MMS,PMS) outcomes and acceptable safety (adverse events
(AEs)/vitals/clinical laboratory test results) and exposure (PK).

- Consider to terminate the study if there is no evidence of drug exposure/efficacy in the
colon observed by endoscopy or biopsy nor evidence of potential overall efficacy (TMS,
MMS, PMS) outcomes or unacceptable safety(AEs/labs/vitals) or exposure (PK).

- Continue the study with the GED-0301 160 mg QD dose. If the GED-0301 160 mg QD dose
group is discontinued and a new dose group is added, an additional 40 subjects will be
enrolled in the new dose group. Subjects enrolled subsequent to the decision to adjust
the dose of GED-0301, will receive the following treatments:

- Induction Phase - GED-0301, up to 320 mg QD, for 8 weeks;

- Extension Phase- GED-0301, up to 320 mg on alternating dosing schedule (GED-0301, up to
320 mg QD for 4 weeks, followed by 4 weeks without GED-0301 treatment) for an additional
44 weeks. Subjects who do not achieve at least a 20% decrease in the PMS from baseline
at Week 12 will be discontinued from the study. Actively enrolled subjects will not be
affected by the dose adjustment. Subjects receiving corticosteroids at baseline will
start tapering their corticosteroids at Week 8 (the end of the Induction Phase) if they
achieve clinical response, defined as a decrease from baseline of at least 2 points and
at least 25%, along with a reduction in the RBS of at least 1 point or an absolute RBS ≤
1 in the MMS. The endoscopy subscore assessed by the investigator will be used for the
calculation of the Week 8 MMS.

The study will consist of 4 phases:

- Screening Phase - up to 4 weeks

- Induction Phase - 8 weeks

- Extension Phase - 44 weeks

- Observational Follow-up Phase - 4 weeks Subjects who complete the Extension Phase, and
those subjects who prematurely discontinue from the study for any reason, will enter the
post-treatment Observational Follow-up Phase, the 4-week period after the last dose of
Investigational Product(IP). The study will be conducted in compliance with
International Conference on Harmonisation (ICH) Good Clinical Practices (GCPs).

Inclusion Criteria:

Inclusion Criteria:

- Subjects must satisfy the following criteria to be enrolled in the study:

1. Subject is ≥ 18 years of age at the time of signing the informed consent form
(ICF).

2. Subject is able to understand and voluntarily sign an informed consent form
(ICF)prior to conducting any study related assessments/procedures.

3. Subject is willing and able to adhere to the study visit schedule and other
protocol requirements.

4. Subject must have diagnosis of Ulcerative Colitis (UC) with a duration of at
least 3 months prior to screening.

5. Subject must have moderate to severe Ulcerative Colitis (UC), defined as Modified
Mayo score (MMS) ≥ 4 to ≤ 9 with rectal bleeding subscore (RBS) ≥ 1 at screening.

6. Subject must have a Mayo endoscopic subscore ≥ 2 at screening.

7. Subject must have failed or experienced intolerance to at least one of the
following:

aminosalicylates; budesonide; systemic corticosteroids; immunosuppressants
(eg,6-mercaptopurine (6-MP), or azathioprine (AZA)) or Tumor necrosis factor
(TNF)-α blockers (eg, infliximab, adalimumab, or golimumab)

8. Subject must meet the following laboratory criteria:

1. White blood cell count ≥ 3000/mm3 (≥ 3.0 X 109/L)

2. Platelet count ≥ 100,000/mm3 (≥ 100 X 109/L)

3. Serum creatinine ≤ 1.5 mg/dL (≤ 132.6 μmol/L)

4. Aspartate transaminase (AST/serum glutamic oxaloacetic transaminase (SGOT))
and alanine transaminase (ALT/serum pyruvic transaminase (SGPT)2.5 X upper
limit of normal (ULN)

5. Total bilirubin ≤ 2 mg/dL (≤ 34 μmol/L) unless there is a confirmed
diagnosis of Gilbert's disease

6. Hemoglobin ≥ 9 g/dL (≥ 5.6 mmol/L)

7. Activated partial thromboplastin time (APTT) 1.5 X ULN

9. Females of childbearing potential (FCBP) must have a negative pregnancy test at
the Screening and Baseline Visits. While on Investigational Product (IP)and for
at least 28 days after taking the last dose of Investigational Product (IP),
females of childbearing potential (FCBP) who engage in activity in which
conception is possible must use one of the approved contraceptive options
described below: Option 1: Any one of the following highly effective methods:
hormonal contraception (oral, injection, implant, transdermal patch, vaginal
ring); intrauterine device (IUD); tubal ligation; or partner's vasectomy; OR
Option 2: Male or female condom PLUS 1 additional barrier method: (a) diaphragm
with spermicide; (b) cervical cap with spermicide; or (c) contraceptive sponge
with spermicide.

10. Male subjects (including those who have had a vasectomy) when engaging in sexual
activity with females who are able to become pregnant must use barrier
contraception (male latex condom or nonlatex condom NOT made out of natural
[animal] membrane [for example, polyurethane]) while on Investigational Product
(IP) and for at least 28 days after the last dose.

Exclusion Criteria:

- The presence of any of the following will exclude a subject from enrollment:

1. Subject has a diagnosis of Crohn's Disease (CD), indeterminate colitis, ischemic
colitis, microscopic colitis, radiation colitis or diverticular
disease-associated colitis.

2. Subject has ulcerative colitis restricted to distal 15 cm or less (eg, ulcerative
proctitis).

3. Subject had surgery as a treatment for ulcerative colitis (UC)or who, in the
opinion of the Investigator, is likely to require surgery for ulcerative colitis
(UC) during the study.

4. Subject has clinical signs suggestive of fulminant colitis or toxic megacolon.

5. Subject is stool positive for any enteric pathogen or Clostridium difficile (C.
difficile) toxin at screening.

6. Subject has history of colorectal cancer or colorectal dysplasia.

7. Prior treatment with more than 2 Tumor necrosis factor (TNF)-α blockers (eg,
infliximab, adalimumab, or golimumab).

8. Prior treatment with any integrin antagonists (eg, natalizumab or vedolizumab).

9. Use of Tumor necrosis factor (TNF)-α blockers within 8 weeks of the screening.

10. Subject had prior treatment with mycophenolic acid, tacrolimus, sirolimus,
cyclosporine, thalidomide or apheresis (eg, Adacolumn®) for the treatment of
ulcerative colitis (UC). In addition, prior use of any of these treatment
modalities for an indication other than ulcerative colitis (UC) within 8 weeks of
screening is also excluded.

11. Subject has received intravenous (IV) corticosteroids within 2 weeks of
screening.

12. Subject has received topical treatment with 5 aminosalicylic acid (5-ASA) or
corticosteroid enemas or suppositories within 2 weeks of screening.

13. Subject has received total parenteral nutrition (TPN) within 4 weeks of
screening.

14. Subject has a history of any clinically significant neurological, renal, hepatic,
gastrointestinal, pulmonary, metabolic, cardiovascular, psychiatric, endocrine,
hematological disorder or disease, or any other medical condition that, in the
investigator's opinion, would prevent the subject from participation in the
study.

15. Subject has any condition, including the presence of laboratory abnormalities,
which places the subject at unacceptable risk if he/she was to participate in the
study or confounds the ability to interpret data from the study.

16. Subject is pregnant or breastfeeding.

17. Subject has a history of any of the following cardiac conditions within 6 months
of screening: myocardial infarction, acute coronary syndrome, unstable angina,
new onset atrial fibrillation, new onset atrial flutter, second- or third-degree
atrioventricular block, ventricular fibrillation, ventricular tachycardia, heart
failure, cardiac surgery, interventional cardiac catheterization (with or without
a stent placement), interventional electrophysiology procedure, or presence of
implanted defibrillator.

18. Subject has a known active current or history of medically important recurrent
bacterial, viral, fungal, mycobacterial or other infections (including but not
limited to tuberculosis and atypical mycobacterial disease and Herpes zoster),
human immunodeficiency virus (HIV), or any major episode of infection requiring
hospitalization or treatment with intravenous (IV) or oral antibiotics within 4
weeks of screening.

19. Subject has a history of congenital or acquired immunodeficiency (eg, common
variable immunodeficiency disease).

20. Subject has a history of malignancy, except for:

1. Treated (ie, cured) basal cell or squamous cell in situ skin carcinomas

2. Treated (ie, cured) cervical intraepithelial neoplasia or carcinoma in situ
of the cervix with no evidence of recurrence within the previous 5 years

21. Subject has received investigational drug or device within 1 month of screening.

22. Subject has a history of alcohol, drug, or chemical abuse within the 6 months
prior to screening.

23. Subject has a known hypersensitivity to oligonucleotides or any ingredient in the
Investigational Product (IP).

24. Subject has prior treatment with GED-0301 or participated in a clinical study
involving GED-0301.