This is a multicenter, randomized, placebo-controlled study to evaluate the long-term efficacy and safety of ABX464 50mg and 25mg administered once daily (QD) as maintenance therapy in subjects with moderately to severely active ulcerative colitis who have inadequate response, no response, a loss of response, or an intolerance to either conventional therapies [corticosteroids, immunosuppressant (i.e. azathioprine, 6-mercaptopurine, methotrexate)] and/or advanced therapies [biologics (TNF inhibitors, anti-integrins, anti-IL-23), and/or S1P receptor modulators, and/or JAK inhibitors].

This study is the maintenance phase of both previous induction studies ABX464-105 and ABX464-106.

All eligible subjects who have completed either one of the induction studies above mentioned, will be given the opportunity to take part in the present ABX464-107 study which consists of 2 treatment phases.

This study consists of a 44-week maintenance treatment phase (Part 1 and Part 2), followed by a 4-year Long Term Extension (LTE) treatment phase and a 28-days follow-up period consisting in the End of Study (EOS) visit.

The maintenance phase is a 44-week double blind, placebo-controlled, phase. Subjects who are clinical responders after 8 weeks induction will be randomized to Part 1, and those who are non-clinical responders will be randomized to Part 2.

At the end of the 44-week maintenance phase, subjects will continue their allocated treatment until the maintenance phase is unblinded.

Once the study is unblinded, all subjects receiving obefazimod will continue their allocated treatment. Subjects receiving placebo will be allocated to obefazimod 25 mg or can terminate the study.

Inclusion Criteria in maintenance phase:

• Subjects must have completed the induction treatment study (ABX464-105 or ABX464-106), and patients' clinical response status must be available.
• Subjects with a valid endoscopy performed at the end of the induction study and results from central reader available at Day 1.
• Subjects must understand, sign and date the written voluntary informed consent form at the visit prior to any protocol-specific procedures. For under-aged subjects, national requirements regarding consent should also be met.
• Women of childbearing potential (WOCBP) subjects and male subjects with WOCBP partner must agree to comply with contraception requirements as described in Section 4.4. (Contraception) of the protocol.
• Subjects must be able and willing to comply with study visits and procedures as per protocol.
• Subjects should be affiliated to a health insurance policy whenever required by a participating country or state

Inclusion criteria in LTE phase:

• Subject must have completed the maintenance phase
• Investigator and subject must assess and agree that the subject has received, and will continue to receive benefit from being in the study

Exclusion Criteria in maintenance phase:

• Subjects who permanently discontinued the study treatment during the induction study (either ABX464-105 or ABX464-106).
• Subjects who have developed any major illness/condition (eg. primary sclerosis cholangitis, Crohn's disease, colectomy, diverting ileostomy, colon cancer or colonic adenomas [low or high grade dysplasia]).
• Subjects with evidence of an unstable clinical condition (eg. toxic megacolon, fulminant colitis, bowel perforation, uncontrolled ischemic disease, congestive heart failure with NYHA class 3 or 4 symptoms) during the induction study that, in the investigator's judgment, will substantially increase the risk to the subject if he or she participates in the study.
• Subjects who plan to participate in other investigational studies during the maintenance study.
• Male or female planning a pregnancy, or pregnant female subjects
• Introduction during induction study of prohibited medications, dosages, surgical or non-medicinal procedures indicated for UC (except antidiarrheals and motility agents for acute diarrhea).
• Any changes in the laboratory values during the induction period that could jeopardize subject's safety in the opinion of the investigator. If any doubts, the investigator should contact the sponsor study medical monitor.
• Subject who is planning to receive live vaccine during the study.
• Subjects committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.

Exclusion criteria for LTE phase:

• Subject continues to satisfy exclusion criteria listed above for the maintenance phase
• Introduction during maintenance phase of prohibited medications, dosages, surgical or non-medicinal procedures indicated for UC (except antidiarrheals and motility agents for acute diarrhea).

All eligible subjects will be randomized to either the double blind, placebo-controlled Part #1 (ABX464 50mg or 25mg or placebo) or randomized to double-blind Part #2 (ABX464 50mg or 25mg) depending on their clinical response at the end of induction.