ABTECT-2 - ABX464 Treatment Evaluation for Ulcerative Colitis Therapy -2

Inclusion Criteria:

• Men or women at least 16 years old; Adolescent subjects will only be enrolled ifapproved by the country regulatory/health authority. If these approvals have notbeen granted, only subjects ≥ 18 years old will be enrolled. To be eligible,adolescent subjects must weigh ≥ 40 kg and meet the definition of Tanner Stage 5 atthe screening visit.

• Subjects must understand, sign and date the written voluntary informed consent format the visit prior to any protocol-specific procedures. For under-aged subjects,national requirements regarding consent should also be met.

• Documented diagnosis of UC confirmed by endoscopy and histology. Shouldendoscopy/histology results not be available at screening, results from endoscopiesand biopsies taken at screening may be used.

• Active disease defined by modified Mayo score (MMS) ≥ 5 with rectal bleedingsubscore (RBS) ≥ 1 and endoscopy subscore (MES) of 2 or 3 (confirmed by centralreader).

• Subjects with documented inadequate response (defined as lack of response or loss ofresponse or intolerance) to at least one of the following treatments:corticosteroids, immunosuppressant, biologic or biosimilar therapies, S1P receptormodulators and/or JAK inhibitors and/or new drugs approved during the study (note:failure to only 5-ASA or sulfasalazine is not accepted).

• Women of childbearing potential (WOCBP) subjects and male subjects with WOCBPpartner must agree to comply with the contraception requirements described in theprotocol.

• Subjects able and willing to comply with study visits and procedures as perprotocol.

• Subjects should be affiliated to a health insurance policy whenever required by aparticipating country or state.

Exclusion Criteria:

• Subjects with UC limited to an isolated proctitis (≤ 15cm from anal verge)determined by endoscopy central reading.

• Subjects with primary sclerosing cholangitis or autoimmune hepatitis.

• Subjects who have failed on 5-ASA or sulfasalazine therapy only.

• Subjects with CD or presence or history of fistula, indeterminate colitis,infectious/ischemic colitis or microscopic colitis (lymphocytic and collagenouscolitis).

• History or current evidence of toxic megacolon, fulminant colitis, bowelperforation.

• History of colonic cancer or colonic low grade or high grade dysplasia adenomatouspolyps, and/or at the screening endoscopy, evidence of colonic cancer or evidence oflow grade or high grade dysplasia adenomatous polyps (fully removed or not).

• Recent or planned bowel surgery or history of proctocolectomy or partial colectomyor current stoma.

• Subjects on antidiarrheals including those working on motility (e.g., loperamide,diphenoxylate with atropine, etc.).

• Subjects on probiotics (e.g., Culturelle® [Lactobacillus GG, i-Health, Inc.],Saccharomyces boulardii).

• Subjects who do not meet the washout period requirements prior to the screeningendoscopy.

• Subjects with the following hematological and biochemical laboratory parametersobtained during the screening period:

• Hemoglobin ≤ 8.0 g dL-1

• Absolute neutrophil count < 750 mm-3

• Platelets < 100,000 mm-3

• Creatinine clearance < 60 mL.min-1 (Cockroft-Gault formula)

• Total serum bilirubin > 1.5 x ULN

• Alkaline phosphatase, aspartate aminotransferase (AST) and alanineaminotransferase (ALT) > 2 x ULN

• Subjects with the following conditions (infection):

• Subjects with chronic or recurrent grade 3 or grade 4 infection within the last 2 months prior to screening or a history of opportunistic infection while noton immunosuppressive therapy.

• Herpes zoster reactivation within the last 2 months prior to screening.

• Subjects with active infection at screening or any major episode of infectionthat required hospitalization or treatment with intravenous antibiotics within 1 month of screening or during screening. Fungal infection of nail beds isallowed.

• Positive assay or stool culture for pathogens (ova and parasite examination,bacteria) or positive test for Clostridium difficile toxin at screening. If C.difficile is positive, subject may be treated and retested ≥ 2 weeks aftercompleting treatment.

• Subjects with HIV infection.

• Subjects having acute or chronic hepatitis B infection at screening (positivefor hepatitis B surface antigen [HbsAg], or negative for HbsAg and positive foranti-hepatitis B core antibody in conjunction with detectable HBV DNA, ordetectable HBV DNA).

• Subjects having acute or chronic hepatitis C infection at screening as definedby positive for hepatitis C antibody (subjects successfully treated and withoutrecurrence ≥ 1 year with no detectable HCV RNA [assessed centrally] areeligible).

• Active tuberculosis (TB) or untreated latent TB are ruled out. For subjectswith positive or intermediate QuantiFERON test see the current study protocol.

• Subjects with an uncontrolled ischemic heart disease and/or a history of congestiveheart failure with New York Heart Association (NYHA) class 3 or 4 symptoms.

• Subjects with a family or personal history of congenital or acquired long QTsyndrome, or subjects with a marked baseline prolongation of QT/QTc interval (e.g.,repeated demonstration of a QTc interval [Fridericia or Bazett correction] >450milliseconds for male and > 460 milliseconds for female).

• Subjects with a history of torsade de pointe (TdP).

• Acute or chronic of clinically relevant pulmonary, hepatic, pancreatic or renalfunctional abnormality, encephalopathy, neuropathy or unstable central nervoussystem pathology such as seizure disorder, or any other clinically significantmedical problems as determined by physical examination and/or laboratory screeningtests and/or medical history (note: treated autoimmune hypothyroidy and autoimmunediabetes are allowed).

• Serious illness requiring hospitalization within 4 weeks prior to screening (exceptUC flare).

• Subjects previously treated with ABX464.

• Subjects with a known hypersensitivity to the active substance or to any of theexcipients.

• WOCBP subject who is pregnant or breast-feeding at screening, or intends to becomepregnant during the study, or male subject with WOCBP partner who intends to bepregnant during the study.

• Illicit drug or alcohol abuse or dependence.

• Subjects who received live vaccine within 3 months prior to screening and/or who'splanning to receive such a vaccine during the study duration.

• Use of any investigational or non-registered product within 3 months or within 5half-lives preceding baseline, whichever is longer, and during the study.

• Subjects committed to an institution by virtue of an order issued either by thejudicial or the administrative authorities.

• Any condition, which in the opinion of the investigator, could compromise thesubject's safety or adherence to the study protocol.