Study of the Efficacy, Safety, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of BCD-261 in Subjects With Moderate to Severe Active Ulcerative Colitis

Inclusion Criteria:

1. Diagnosis of ulcerative colitis with involvement of the colon proximal to the rectum (≥15 cm from the distal edge of the anal canal), established ≥3 months before signing the ICF and confirmed by endoscopic examination data.

2. Moderate to severe active ulcerative colitis with a modified Mayo score (mMS) of ≥4 and ≤9 points, which includes an endoscopic component of ≥2 points (according to a central independent review) and a stool blood score of ≥1 point.

3. Inadequate response to therapy according to the investigator's assessment, manifested by at least one of the following signs:

4. Persistent symptoms of disease activity despite treatment with at least one courseof glucocorticoids including prednisolone at a dose of ≥40 mg/day or equivalent orbudesonide ≥9 mg/day or equivalent for at least 2 weeks with oral administration (atleast 1 week with intravenous administration at a dose equivalent to oralprednisolone ≥40 mg/day).

5. Steroid dependence manifested by an increase in disease activity after initialimprovement, with a decrease in the dose of glucocorticoids below the doseequivalent to 10 mg of oral prednisolone per day, within 3 months from the beginningof treatment, or a relapse of the disease within 3 months after the end ofglucocorticoid use.

6. Persistent symptoms of disease activity despite treatment with at least one courseof immunosuppressants (azathioprine at a dose of ≥2.0 mg/kg and/or 6-mercaptopurineat a dose of ≥1.0 mg/kg) for ≥12 weeks, or in response to another treatment regimenwith these drugs according to a regional standard of care.

7. Primary lack of response to therapy with TNFa inhibitors and/or anti-integrins,and/or IL-12/23 inhibitors, and/or Janus kinase inhibitors, and/orsphingosine-1-phosphate receptor modulators, defined as the persistence of symptomsof disease activity despite at least one course of induction of remission accordingto a treatment scheme approved by the regional standard.

8. Loss of response to therapy with TNFa inhibitors and/or anti-integrins, and/orIL-12/23 inhibitors, and/or Janus kinase inhibitors, and/or sphingosine-1-phosphatereceptor modulators, defined as the appearance of symptoms of disease activity afterinitial improvement as a result of treatment with at least one course of inductionof remission and at least one course of maintenance of remission according to atreatment scheme approved by the regional standard.

9. A history of intolerance to glucocorticoids and/or immunosuppressants (azathioprine, 6-mercaptopurine) and/or biological therapy/targeted immunosuppressants (TNFainhibitors, anti-integrins, anti-IL-12/23 monoclonal antibodies, Janus kinaseinhibitors, sphingosine-1-phosphate receptor modulators) established by the treatingphysician.

10. Maintaining a stable dose of concomitant medications for ≥2 weeks prior to signing the ICF and in the screening period for glucocorticoids and 5-ASCs and for ≥4 weeks prior to signing the ICF and in the screening period for immunosuppressants (azathioprine, 6-mercaptopurine).

Exclusion Criteria:

1. A history of or current at the time of signing the ICF Crohn's disease, unspecifiedcolitis, ischemic colitis, radiation colitis, microscopic colitis, complicated formof diverticular disease.

2. A history of primary sclerosing cholangitis.

3. A history of fulminant colitis, toxic dilation of the colon, intestinal obstruction,intestinal perforation (except for those caused by injury or appendicitis).

4. A history of dysplasia of any grade in any part of the gastrointestinal tract at thetime of signing the ICF.

5. Presence of intestinal stoma or artificial rectum or the need for them.

6. Failure of ≥3 classes of biologics/targeted immunosuppressors (according to INN)with different mechanisms of action (TNFa inhibitors, anti-integrins, IL-12/23inhibitors, Janus kinase inhibitors, sphingosine-1-phosphate receptor modulators) or ≥4 biologics/targeted immunosuppressants, regardless of the mechanism of action.

7. Use of any of the indicated therapies within the specified time frame or need fortherapy with these drugs during the study period:

(1) Use of Janus kinase inhibitors within 2 weeks prior to signing the ICF or during the screening period.

(2) Use of TNFa inhibitors within 8 weeks prior to signing the ICF or during the screening period.

(3) Using modulators of sphingosine-1-phosphate receptors within 10 weeks prior to signing the ICF or during the screening period.

(4) Use of anti-integrins, IL-12/23 inhibitors within 12 weeks before signing the ICF or during the screening period.

(5) Use of oral glucocorticoids at a dose equivalent to prednisone >20 mg/day or budesonide >9 mg/day or rectal administration of glucocorticoids at any dose within

2 weeks prior to signing the ICF or during the screening period or parenteral administration of glucocorticoids at any dose within 4 weeks prior to signing the ICF or during the screening period.

(6) Rectal administration of 5-ASCs within 2 weeks prior to signing the ICF or during the screening period.

(7) Use of immunosuppressants not included in the approved therapy (tacrolimus, cyclosporine, mycophenolate mofetil, rapamycin, leflunomide, penicillamine, etc.) within 4 weeks before signing the ICF or during the screening period.

(8) Long-term regular use of non-steroidal anti-inflammatory drugs (≥3 times a week for ≥6 weeks) for 2 weeks prior to signing the ICF.

(9) Use of any other investigational drugs in other clinical trials at the time of signing the ICF or less than 8 weeks or 5 half-lives (whichever is longer) before the date of randomization.