Inclusion Criteria Induction:  Male or female ≥ 18 years of age. Established diagnosis of UC. Moderate to severe active left-sided UC assessed by central reading. Have inadequate response, loss of response or be intolerant of at least one of the following treatments: Oral GCS, AZA/6-MP, Biologics, JAK-inhibitors, or other approved advanced therapies for UC. Allowed to receive a therapeutic dose of the following UC drugs during the study: Oral GCS therapy (≤20 mg prednisone or equivalent/day) , Oral 5-ASA/SP compounds, AZA/6-MP. Ability to understand the treatment, willingness to comply with all study requirements, and ability to provide informed consent.  Exclusion Criteria Induction:  Suspicion of differential diagnosis. Acute fulminant UC and/or signs of systemic toxicity. UC limited to the rectum or extending beyond the splenic flexure. Have failed treatment with more than three advanced therapies of two different therapeutic classes. Have had surgery for treatment of UC. History of malignancy, unless treated with no relapse of the disease and ≥ 5 years since last treatment (cured). History or presence of any clinically significant disorder. Concomitant treatment with cyclosporine, methotrexate, tacrolimus, or advanced therapies or similar immunosuppressants and immunomodulators. Treatment with rectal GCS, 5-ASA/SP or tacrolimus. Long-term treatment (>14 days) with antibiotics or NSAIDs . Serious known active infection including history of latent or active tuberculosis. Gastrointestinal infections including positive Clostridium difficile stool assay. Females who are lactating or have a positive serum pregnancy test. Women of childbearing potential not using highly effective contraceptive methods. Concurrent participation in another clinical study. Previous exposure to cobitolimod.  Inclusion Criteria Maintenance:  Participants are eligible to be included in the maintenance study if they have achieved clinical response at week 6 and have adhered to the protocol procedures of the induction study.  Exclusion Criteria Maintenance:  Participants will not be eligible for the maintenance study if they are not willing to comply with all further study requirements.