Clinical Study of the Efficacy, Safety, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of BCD-261 in Subjects With Moderate to Severe Active Crohn's Disease

Inclusion Criteria:

1. The diagnosis of Crohn's disease involving the terminal ileum or colon (types L1-L3according to the Montreal classification), established ≥3 months prior to signingthe informed consent form and confirmed by endoscopic findings.

2. Moderate to severe active Crohn's disease, manifested by the following signs:

(1) Crohn's Disease Activity Index (CDAI) ≥220 and ≤450 points.

(2) Simple Endoscopic Score for Crohn's Disease (SES-CD) ≥6 points or ≥4 points for the disease form with isolated involvement of the ileum (according to central independent review).

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 and/or methotrexate at a dose of ≥15.0 mg/week) for ≥12weeks, or in response to another treatment regimen with these drugs according to aregional 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 targeted immunosuppressors (upadacitinib),defined as the persistence of symptoms of disease activity despite at least onecourse of induction of remission according to a treatment scheme approved by theregional standard.

8. Loss of response to therapy with TNFa inhibitors and/or anti-integrins, and/orIL-12/23 inhibitors, and/or targeted immunosuppressors (upadacitinib), defined asthe appearance of symptoms of disease activity after initial improvement as a resultof treatment with at least one course of induction of remission and at least onecourse of maintenance of remission according to a treatment scheme approved by theregional standard.

9. A history of intolerance to glucocorticoid therapy and/or immunosuppressors (azathioprine, 6-mercaptopurine, methotrexate) and/or biologic therapies (TNFαinhibitors, anti-integrins, IL-12/23 inhibitors) and/or targeted immunosuppressors (upadacitinib), as determined by the treating physician.

10. Maintaining a stable dose of concomitant medications for ≥2 weeks prior to signing the ICF and in the screening period for glucocorticoids and for ≥4 weeks prior to signing the

ICF and in the screening period for immunosuppressants (azathioprine, 6-mercaptopurine, methotrexate).

Exclusion Criteria:

1. A history of or current at the time of signing the ICF ulcerative colitis,unspecified colitis, ischemic colitis, radiation colitis, microscopic colitis,complicated form of diverticular disease.

2. A history of primary sclerosing cholangitis.

3. Presence of active intra-abdominal or perianal abscess at the time of signing theICF.

4. Presence of an endoscopically obstructed stricture/stenosis of the intestine at thetime of signing the ICF.

5. A history of toxic megacolon, intestinal obstruction, intestinal perforation (exceptfor those caused by injury or appendicitis).

6. A history of dysplasia in any part of the gastrointestinal tract at the time ofsigning the ICF.

7. Previous resections of the small intestine with a total length of resected segments >100 cm and/or resection of >2 segments of the large intestine (ascending colon (including the cecum), transverse colon, descending colon (including the sigmoidcolon), rectum)3.

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

9. Failure of ≥3 classes of biologics/targeted immunosuppressors (according to INN)with different mechanisms of action (TNFa inhibitors, anti-integrins, IL-12/23inhibitors, upadacitinib) or ≥4 biologics/targeted immunosuppressants (according toINN), regardless of the mechanism of actio

• Use of any of the indicated therapies within the specified time frame or needfor therapy with these drugs during the study period:

1. Use of TNFa inhibitors within 8 weeks prior to signing the ICF or duringthe screening period.
2. Use of anti-integrins or IL-12/23 inhibitors within 12 weeks beforesigning the ICF or during the screening period.
3. Use of Janus kinase inhibitors (upadacitinib) within 2 weeks prior tosigning the ICF or during the screening period.
4. Use of oral glucocorticoids at a dose equivalent to prednisone >20 mg/dayor budesonide >9 mg/day or rectal administration of glucocorticoids at anydose within 2 weeks prior to signing the ICF or during the screeningperiod or parenteral administration of glucocorticoids at any dose within 4 weeks prior to signing the ICF or during the screening period.
5. 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 thescreening period.
6. Long-term regular use of non-steroidal anti-inflammatory drugs (≥3 times aweek for ≥6 weeks) for 2 weeks prior to signing the ICF.
7. Use of any other investigational drugs in other clinical trials at thetime of signing the ICF or less than 8 weeks or 5 half-lives (whichever islonger) before the date of signing the ICF or during screening.