Methods for treating inflammatory bowel disease caused by anti-TL1A antibodies

Abstract

This disclosure provides methods and compositions for treating inflammatory bowel disease (IBD), such as ulcerative colitis (UC) or Crohn's disease (CD), using therapeutic doses of anti-TNF-like ligand 1A (TL1A) antibodies.

Description

[Technical Field]

[0001] Sequence List This application includes a sequence listing submitted electronically in XML format, which is incorporated herein by reference in its entirety. The XML copy, created on 13 May 2025, is named 50474-353WO5_Sequence_Listing_5_13_25 and has a size of 75,543 bytes.

[0002] Technical field The present invention relates to the treatment of signs and symptoms of inflammatory bowel disease (IBD), such as ulcerative colitis (UC) or Crohn's disease (CD), using an antitumor necrosis factor-like ligand 1A (TL1A) antibody. [Background technology]

[0003] Background of the Invention Inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis (UC), is a chronic inflammatory disorder affecting approximately 1.6 million people in the United States and 2.5 to 3 million people in Europe.

[0004] The goal of medical treatment in IBD is to control inflammation and reduce symptoms. Treatment options available for moderate to severe active UC include appropriate doses of oral corticosteroids; biological therapies such as tumor necrosis factor inhibitors (TNFis) infliximab, adalimumab, ustekinumab, and golimumab; the integrin receptor antagonist vedolizumab; and the orally administered small molecule Janus kinase inhibitor tofacitinib. However, unresponsiveness, insufficient response, and loss of response to these and other treatments are known to occur, and these treatments may have significant adverse effects. Therefore, the development of novel treatments for IBD (e.g., UC and CD) leaves an unmet clinical need.

[0005] One of the immune components involved in the pathogenesis of IBD is TNF-like ligand 1A (TL1A, also known as tissue necrosis factor superfamily member 15 (TNFSF15)). Genome-wide association studies have linked TNFSF15 single nucleotide polymorphisms (SNPs) to disease severity; for example, an association was observed between the rs11554257 SNP and medically refractory UC compared to healthy controls (Haritunians et al., Inflammatory Bowel Diseases; 16:1830-1840, 2010). TL1A has been found to be upregulated in IBD tissue specimens, and its expression level corresponds to disease severity (Bamias et al., Clin Immunol; 137:242-249, 2010). TL1A promotes inflammation and intestinal fibrosis in IBD. Furthermore, variants in TNFSF15 have been linked to the pathogenesis of several autoimmune diseases, including psoriasis, rheumatoid arthritis, and multiple sclerosis, suggesting a broad role of TNFSF15 in human inflammatory diseases.

[0006] The binding of TL1A to its receptor, cell death receptor 3 (DR3), stimulates T cell-mediated signaling and cytokine production. Since increased cytokine production leads to chronic inflammation, inhibition of TL1A is a promising therapeutic strategy for treating inflammatory diseases, including IBD.

[0007] Therefore, there is a need in the art for methods to treat inflammatory bowel diseases, including Crohn's disease and ulcerative colitis, using anti-TNF-like ligand 1A (TL1A) antibody therapy. This disclosure addresses these needs. [Overview of the project]

[0008] Summary of the Invention In one embodiment, the present disclosure provides a method for treating a patient with inflammatory bowel disease (IBD), the method comprising administering an effective amount of anti-TNF-like ligand 1A (TL1A) antibody to the patient in a dosing regimen including an induction phase, the induction phase comprising only four doses of anti-TL1A antibody, (i) the second dose of anti-TL1A antibody being administered approximately two weeks after the first dose; (ii) the third dose of anti-TL1A antibody being administered approximately four weeks after the second dose; and (iii) the anti-TL1A antibody The fourth dose is administered approximately four weeks after the third dose; the anti-TL1A antibody comprises the following complementarity-determining regions (CDRs): (a) CDR-H1 containing the amino acid sequence of SEQ ID NO: 3; (b) CDR-H2 containing the amino acid sequence of SEQ ID NO: 4; (c) CDR-H3 containing the amino acid sequence of SEQ ID NO: 5; (d) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6; (e) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7; and (f) CDR-L3 containing the amino acid sequence of SEQ ID NO: 8. In some embodiments, the drug regimen further includes a maintenance phase.

[0009] In another aspect, the Disclosure provides a method for treating IBD in a patient, the method comprising administering an effective amount of anti-TL1A antibody to the patient in a dosing regimen including an induction phase and a maintenance phase, (a) the induction phase comprising only four doses of anti-TL1A antibody, (i) the second dose of anti-TL1A antibody being administered approximately two weeks after the first dose; (ii) the third dose of anti-TL1A antibody being administered approximately four weeks after the second dose; and (iii) the fourth dose of anti-TL1A antibody being administered approximately four weeks after the third dose (b) The maintenance phase is performed approximately 4 weeks later; (b) the maintenance phase includes administration of anti-TL1A antibodies every 4 weeks, the anti-TL1A antibodies including the following CDRs: (a) CDR-H1 containing the amino acid sequence of SEQ ID NO: 3; (b) CDR-H2 containing the amino acid sequence of SEQ ID NO: 4; (c) CDR-H3 containing the amino acid sequence of SEQ ID NO: 5; (d) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6; (e) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7; and (f) CDR-L3 containing the amino acid sequence of SEQ ID NO: 8.

[0010] In some embodiments, during the induction phase, the anti-TL1A antibody is administered intravenously at a dose of approximately 500 mg.

[0011] In some embodiments, during the induction phase, the anti-TL1A antibody is administered subcutaneously at a dose of about 500 mg.

[0012] In some embodiments, the induction phase has a duration of about 12 weeks. In some embodiments, (a) the first administration of the anti-TL1A antibody is performed around the first day of week 0; (b) the second administration of the anti-TL1A antibody is performed around the first day of week 2; (c) the third administration of the anti-TL1A antibody is performed around the first day of week 6; and (d) the fourth administration of the anti-TL1A antibody is performed around the first day of week 10.

[0013] In some embodiments, during the maintenance phase, the anti-TL1A antibody is administered subcutaneously at a dose of about 150 mg. In some embodiments, during the maintenance phase, the anti-TL1A antibody is administered subcutaneously at a dose of about 450 mg.

[0014] In some embodiments, the maintenance phase includes at least two administrations of the anti-TL1A antibody.

[0015] In some embodiments, the maintenance phase includes subcutaneous administration of the anti-TL1A antibody every four weeks. In some embodiments, the maintenance phase includes subcutaneous administration of the anti-TL1A antibody every two weeks. In some embodiments, the maintenance phase includes (i) at least one interval in which the anti-TL1A antibody is administered every four weeks and (ii) at least one interval in which the anti-TL1A antibody is administered every two weeks.

[0016] In some embodiments, the maintenance phase includes 11 administrations of the anti-TL1A antibody.

[0017] In some embodiments, the maintenance phase has a duration of about 40 weeks.

[0018] In some embodiments where the method includes a maintenance phase, corticosteroids are administered to the patient daily during the induction phase, and the dose of corticosteroids is tapered during the maintenance phase. In some embodiments, the administration of corticosteroids is discontinued during the maintenance phase.

[0019] In some embodiments, the corticosteroid is prednisone or its equivalent, budesonide, or budesonide multimatrix (MMX). In some embodiments, the corticosteroid is prednisone or its equivalent, administered orally to the patient in a dose greater than 10 mg per day during the induction phase, and tapering includes (i) tapering the dose by 5 mg per week until the patient receives a dose of 10 mg per day; and (ii) tapering the dose by 2.5 mg per week until a dose of 0 mg per week is reached. In some embodiments, the corticosteroid is prednisone or its equivalent, administered orally to the patient in a dose of 10 mg or less per day during the induction phase, and tapering includes tapering the dose by 2.5 mg per week until a dose of 0 mg per week is reached. In some embodiments, the corticosteroid is budesonide or budesonide MMX, which is administered orally to the patient at a dose of 9 mg or less per day during the induction phase, and tapering includes (i) administering a dose of 9 mg of the corticosteroid every other day for two weeks; (ii) administering a dose of 9 mg of the corticosteroid every three days for two weeks; and (iii) discontinuing the administration of the corticosteroid.

[0020] In some embodiments of the method, including the maintenance phase, the first dose of the maintenance phase is administered approximately two weeks after the fourth dose of the induction phase.

[0021] In some embodiments, the medication regimen has a duration of approximately 52 weeks. In some embodiments, (a) the first dose of the induction phase is given around day 1 of week 0; (b) the second dose of the induction phase is given around day 1 of week 2; (c) the third dose of the induction phase is given around day 1 of week 6; (d) the fourth dose of the induction phase is given around day 1 of week 10; (e) the first dose of the maintenance phase is given around day 1 of week 12; and (f) subsequent doses of the maintenance phase are given around day 1 of weeks 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52.

[0022] In some embodiments, the medication regimen further includes an extension phase, which includes the administration of one or more additional cycles of anti-TL1A antibody. In some embodiments, (a) the extension phase includes subcutaneous administration of anti-TL1A antibody every four weeks; (b) the extension phase includes subcutaneous administration of anti-TL1A antibody every two weeks; or (c) the extension phase includes (i) at least one interval in which anti-TL1A antibody is administered every four weeks and (ii) at least one interval in which anti-TL1A antibody is administered every two weeks. In some embodiments, one or more cycles of medication in the extension phase are administered to the patient after a disease exacerbation during the maintenance phase.

[0023] In some embodiments, IBD is ulcerative colitis (UC). In some embodiments, UC is moderate to severe active ulcerative colitis. In some embodiments, the patient has a modified Mayo score (mMS) between 5 and 9 points. In some embodiments, the patient has a Mayo endoscopic score (ES) of 2 or 3.

[0024] In some embodiments, IBD is Crohn's disease (CD). In some embodiments, CD is moderate to severely active CD. In some embodiments, (a) the patient has a Simplified Crohn's Disease Score (SES-CD) of 6 or higher; or (b) the patient has only isolated ileal disease and has an SES-CD of 4 or higher. In some embodiments, the patient has a Crohn's Disease Activity Index (CDAI) of at least 220 and ≤ 450.

[0025] In some embodiments, the patient has been previously treated for UC or CD and has experienced an inadequate response to treatment, loss of response to treatment, and / or intolerance to treatment.

[0026] In some embodiments, the treatment was conventional treatment. In some embodiments, conventional treatment included the administration of steroids, immunomodulators, or oral aminosalicylates.

[0027] In some embodiments, the treatment was an advanced treatment. In some embodiments, the advanced treatment included the administration of an antitumor necrosis factor (TNF) agent, an antiintegrin agent, an anti-IL12 / IL23 agent, a Janus kinase (JAK) inhibitor, or a sphingosine-1-phosphate (S1P) inhibitor.

[0028] In another aspect, the present disclosure provides a method for treating a patient with ulcerative colitis (UC), the method comprising administering an effective amount of anti-TNF-like ligand 1A (TL1A) antibody to the patient in a drug regimen including an induction phase and a maintenance phase, (a) the induction phase comprising only four intravenous administrations of anti-TL1A antibody in doses of approximately 500 mg each, (i) the second administration of anti-TL1A antibody being given approximately two weeks after the first administration; (ii) the third administration of anti-TL1A antibody being given approximately four weeks after the second administration; and (iii) the fourth administration of anti-TL1A antibody (b) The maintenance phase is performed approximately four weeks after the third dose; (b) the maintenance phase consists of subcutaneous administration of anti-TL1A antibody at a dose of approximately 450 mg every four weeks, the anti-TL1A antibody comprising the following CDRs: (a) CDR-H1 containing the amino acid sequence of SEQ ID NO: 3; (b) CDR-H2 containing the amino acid sequence of SEQ ID NO: 4; (c) CDR-H3 containing the amino acid sequence of SEQ ID NO: 5; (d) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6; (e) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7; and (f) CDR-L3 containing the amino acid sequence of SEQ ID NO: 8.

[0029] In some embodiments of patients with UC, the treatment according to this method results in an increased proportion of patients achieving clinical remission at the end of the induction period compared to the reference population. In some embodiments, the induction period has a duration of approximately 12 weeks, and the treatment results in an increased proportion of patients achieving clinical remission at week 12.

[0030] In some embodiments of patients with UC, the treatment in the patient population treated according to this method results in an increased proportion of patients achieving clinical remission at the end of the maintenance phase compared to the reference population. In some embodiments, the medication regimen has a duration of approximately 52 weeks, and the treatment results in an increased proportion of patients achieving clinical remission at week 52.

[0031] In some manifestations of UC in patients, clinical remission is defined as a modified Mayo score (mMS) ≤ 2, with a bowel movement frequency subscore (SFS) = 0 or 1, a rectal bleeding subscore (RBS) = 0, and an endoscopic subscore (ES) = 0 or 1.

[0032] In another aspect, the Disclosure provides a method for treating Crohn's disease (CD) in a patient, the method comprising administering an effective amount of anti-TNF-like ligand 1A (TL1A) antibody to the patient in a drug regimen including an induction phase and a maintenance phase, (a) the induction phase comprising only four intravenous administrations of anti-TL1A antibody in doses of approximately 500 mg each, (i) the second administration of anti-TL1A antibody being given approximately two weeks after the first administration; (ii) the third administration of anti-TL1A antibody being given approximately four weeks after the second administration; and (iii) the fourth administration of anti-TL1A antibody (b) The administration is performed approximately four weeks after the third dose; (b) The maintenance phase consists of subcutaneous administration of anti-TL1A antibody at a dose of approximately 450 mg every four weeks, the anti-TL1A antibody comprising the following CDRs: (a) CDR-H1 containing the amino acid sequence of SEQ ID NO: 3; (b) CDR-H2 containing the amino acid sequence of SEQ ID NO: 4; (c) CDR-H3 containing the amino acid sequence of SEQ ID NO: 5; (d) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6; (e) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7; and (f) CDR-L3 containing the amino acid sequence of SEQ ID NO: 8.

[0033] In another aspect, the Disclosure provides a method for treating CD, the method comprising administering an effective amount of anti-TL1A antibody to a patient in a dosing regimen including an induction phase and a maintenance phase, (a) the induction phase comprising only four intravenous administrations of anti-TL1A antibody in doses of approximately 500 mg each, (i) the second dose of anti-TL1A antibody being administered approximately two weeks after the first dose; (ii) the third dose of anti-TL1A antibody being administered approximately four weeks after the second dose; and (iii) the fourth dose of anti-TL1A antibody being administered approximately four weeks after the third dose. (b) The maintenance phase is performed four weeks later; (b) the maintenance phase consists of subcutaneous administration of anti-TL1A antibody at a dose of approximately 150 mg every four weeks, the anti-TL1A antibody comprising the following CDRs: (a) CDR-H1 containing the amino acid sequence of SEQ ID NO: 3; (b) CDR-H2 containing the amino acid sequence of SEQ ID NO: 4; (c) CDR-H3 containing the amino acid sequence of SEQ ID NO: 5; (d) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6; (e) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7; and (f) CDR-L3 containing the amino acid sequence of SEQ ID NO: 8.

[0034] In some embodiments where patients have CD, the treatment according to this method results in an increased proportion of patients achieving clinical remission at the end of the induction period compared to the reference population. In some embodiments, the induction period has a duration of approximately 12 weeks, and the treatment results in an increased proportion of patients achieving clinical remission at week 12.

[0035] In some embodiments of patient populations treated according to this method, where patients have CD, the treatment results in an increased proportion of patients achieving clinical remission at the end of the maintenance phase compared to the reference population. In some embodiments, the medication regimen has a duration of approximately 52 weeks, and the treatment results in an increased proportion of patients achieving clinical remission at week 52.

[0036] In some manifestations of Crohn's disease (CD), clinical remission is defined as a Crohn's disease activity index (CDAI) of less than 150.

[0037] In some embodiments where patients have CD, the treatment according to this method results in an increased proportion of patients achieving an endoscopic response at the end of the induction phase compared to the reference population. In some embodiments, the induction phase lasts for approximately 12 weeks, and the treatment results in an increased proportion of patients achieving an endoscopic response at 12 weeks.

[0038] In some embodiments where patients have CD, the treatment results in an increased proportion of patients achieving an endoscopic response at the end of the maintenance phase compared to the reference population in the patient population treated according to this method. In some embodiments, the drug regimen has a duration of approximately 52 weeks, and the treatment results in an increased proportion of patients achieving an endoscopic response at week 52.

[0039] In some embodiments of Crohn's disease (CD), the endoscopic response is a simplified Crohn's disease endoscopic score (SES-CD) that is at least 50% lower than the baseline SES-CD.

[0040] In some embodiments, the reference population is a group of patients who have never been treated with an anti-TL1A antibody. In some embodiments, the reference population is a group of patients treated with a placebo.

[0041] In some cases, patients are determined to be non-carriers of haplotype B of TNFSF15.

[0042] In some embodiments, the anti-TL1A antibody comprises (a) a heavy chain variable (VH) domain having at least 95% sequence identity with the amino acid sequence of SEQ ID NO: 1; and / or (b) a light chain variable (VL) domain having at least 95% sequence identity with the amino acid sequence of SEQ ID NO: 2.

[0043] In some embodiments, the anti-TL1A antibody comprises (a) a VH domain containing the amino acid sequence of SEQ ID NO: 1; and / or (b) a VL domain containing the amino acid sequence of SEQ ID NO: 2.

[0044] In some embodiments, the anti-TL1A antibody comprises (a) a heavy chain containing an amino acid sequence having at least 95% sequence identity with the amino acid sequence of SEQ ID NO: 9 or SEQ ID NO: 11; and / or (b) a light chain containing an amino acid sequence having at least 95% sequence identity with the amino acid sequence of SEQ ID NO: 10. In some embodiments, the anti-TL1A antibody comprises (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 9; and / or (b) a light chain containing the amino acid sequence of SEQ ID NO: 10. In some embodiments, the anti-TL1A antibody comprises (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 9; and (b) a light chain containing the amino acid sequence of SEQ ID NO: 10.

[0045] In some embodiments, the anti-TL1A antibody is afimkibart.

[0046] In another embodiment, the Disclosure provides a method for treating a patient's inflammatory bowel disease (IBD), the method comprising administering an effective amount of anti-TNF-like ligand 1A (TL1A) antibody to the patient in a dosing regimen including an induction phase, the induction phase comprising only four doses of anti-TL1A antibody, (i) the second dose of anti-TL1A antibody is administered approximately two weeks after the first dose; (ii) the third dose of anti-TL1A antibody is administered approximately four weeks after the second dose; and (iii) the fourth dose of anti-TL1A antibody is administered approximately four weeks after the third dose; the anti-TL1A antibody comprises (a) a heavy chain having at least 95% sequence identity with SEQ ID NO: 9 or having an amino acid sequence of SEQ ID NO: 9; and (b) a light chain having at least 95% sequence identity with SEQ ID NO: 10 or having an amino acid sequence of SEQ ID NO: 10. In some embodiments, IBD is UC. In some embodiments, IBD is CD.

[0047] In another embodiment, the Disclosure provides a method for treating IBD, the method comprising administering an effective amount of anti-TL1A antibody to a patient in a dosing regimen comprising an induction phase and a maintenance phase, (a) the induction phase comprising only four doses of anti-TL1A antibody, (i) the second dose of anti-TL1A antibody being administered about two weeks after the first dose; (ii) the third dose of anti-TL1A antibody being administered about four weeks after the second dose; and (iii) the fourth dose of anti-TL1A antibody being administered about four weeks after the third dose; and (b) the maintenance phase comprising administration of anti-TL1A antibody every four weeks; the anti-TL1A antibody comprising (a) a heavy chain having at least 95% sequence identity with SEQ ID NO: 9 or having an amino acid sequence of SEQ ID NO: 9; and (b) a light chain having at least 95% sequence identity with SEQ ID NO: 10 or having an amino acid sequence of SEQ ID NO: 10. In some embodiments, IBD is UC. In some embodiments, IBD is a CD.

[0048] In some cases, the patient is a human being.

[0049] In some embodiments, the anti-TL1A antibody is administered in combination with one or more additional therapeutic agents.

[0050] In another aspect, the Disclosure provides a kit comprising an anti-TNF-like ligand 1A (TL1A) antibody and a package insert containing instructions for using the antibody to treat inflammatory bowel disease (IBD) in patients requiring treatment of IBD, according to one of the methods provided herein.

[0051] In another aspect, the Disclosure provides an anti-TL1A antibody for use in the treatment of a patient's IBD, wherein an effective amount of the anti-TL1A antibody is administered to the patient in a dosing regimen including an induction phase, the induction phase comprising only four doses of the anti-TL1A antibody, (i) the second dose of the anti-TL1A antibody is administered approximately two weeks after the first dose; (ii) the third dose of the anti-TL1A antibody is administered approximately four weeks after the second dose; and (iii) the fourth dose of the anti-TL1A antibody The first dose will be administered approximately four weeks after the third dose; the anti-TL1A antibody will contain the following complementarity-determining regions (CDRs): (a) CDR-H1 containing the amino acid sequence of SEQ ID NO: 3; (b) CDR-H2 containing the amino acid sequence of SEQ ID NO: 4; (c) CDR-H3 containing the amino acid sequence of SEQ ID NO: 5; (d) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6; (e) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7; and (f) CDR-L3 containing the amino acid sequence of SEQ ID NO: 8.

[0052] In another aspect, the Disclosure provides an anti-TL1A antibody for use in the treatment of a patient's IBD, wherein an effective amount of the anti-TL1A antibody is administered to the patient in a dosing regimen including an induction phase and a maintenance phase, (a) the induction phase comprising only four doses of the anti-TL1A antibody, (i) the second dose of the anti-TL1A antibody being administered approximately two weeks after the first dose; (ii) the third dose of the anti-TL1A antibody being administered approximately four weeks after the second dose; and (iii) the fourth dose of the anti-TL1A antibody (b) The maintenance phase will be performed approximately four weeks after the third dose; (b) the maintenance phase will consist of administration of anti-TL1A antibodies every four weeks, the anti-TL1A antibodies including the following CDRs: (a) CDR-H1 containing the amino acid sequence of SEQ ID NO: 3; (b) CDR-H2 containing the amino acid sequence of SEQ ID NO: 4; (c) CDR-H3 containing the amino acid sequence of SEQ ID NO: 5; (d) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6; (e) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7; and (f) CDR-L3 containing the amino acid sequence of SEQ ID NO: 8.

[0053] In another embodiment, the Disclosure provides an anti-TL1A antibody for use in the treatment of a patient's UC, wherein an effective amount of the anti-TL1A antibody is administered to the patient in a dosing regimen including an induction phase and a maintenance phase, (a) the induction phase comprising only four intravenous doses of approximately 500 mg of the anti-TL1A antibody, (i) the second dose of the anti-TL1A antibody being administered approximately two weeks after the first dose; (ii) the third dose of the anti-TL1A antibody being administered approximately four weeks after the second dose; and (iii) the fourth dose of the anti-TL1A antibody being administered (b) The maintenance phase will be performed approximately four weeks after the third dose; (b) the maintenance phase will consist of subcutaneous administration of approximately 450 mg of anti-TL1A antibody every four weeks, the anti-TL1A antibody including the following CDRs: (a) CDR-H1 containing the amino acid sequence of SEQ ID NO: 3; (b) CDR-H2 containing the amino acid sequence of SEQ ID NO: 4; (c) CDR-H3 containing the amino acid sequence of SEQ ID NO: 5; (d) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6; (e) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7; and (f) CDR-L3 containing the amino acid sequence of SEQ ID NO: 8.

[0054] In another embodiment, the Disclosure provides an anti-TL1A antibody for use in the treatment of a patient’s CD, wherein an effective amount of the anti-TL1A antibody is administered to the patient in a dosing regimen including an induction phase and a maintenance phase, (a) the induction phase comprising only four intravenous doses of approximately 500 mg of the anti-TL1A antibody, (i) the second dose of the anti-TL1A antibody being administered approximately two weeks after the first dose; (ii) the third dose of the anti-TL1A antibody being administered approximately four weeks after the second dose; and (iii) the fourth dose of the anti-TL1A antibody being administered (b) The maintenance phase will be performed approximately four weeks after the third dose; (b) the maintenance phase will consist of subcutaneous administration of approximately 450 mg of anti-TL1A antibody every four weeks, the anti-TL1A antibody including the following CDRs: (a) CDR-H1 containing the amino acid sequence of SEQ ID NO: 3; (b) CDR-H2 containing the amino acid sequence of SEQ ID NO: 4; (c) CDR-H3 containing the amino acid sequence of SEQ ID NO: 5; (d) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6; (e) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7; and (f) CDR-L3 containing the amino acid sequence of SEQ ID NO: 8.

[0055] In another embodiment, the Disclosure provides an anti-TL1A antibody for use in the treatment of a patient’s CD, wherein an effective amount of the anti-TL1A antibody is administered to the patient in a dosing regimen including an induction phase and a maintenance phase, (a) the induction phase comprising only four intravenous doses of approximately 500 mg of the anti-TL1A antibody, (i) the second dose of the anti-TL1A antibody being administered approximately two weeks after the first dose; (ii) the third dose of the anti-TL1A antibody being administered approximately four weeks after the second dose; and (iii) the fourth dose of the anti-TL1A antibody being administered (b) The maintenance phase will be performed approximately four weeks after the third dose; (b) the maintenance phase will consist of subcutaneous administration of approximately 150 mg of anti-TL1A antibody every four weeks, the anti-TL1A antibody including the following CDRs: (a) CDR-H1 containing the amino acid sequence of SEQ ID NO: 3; (b) CDR-H2 containing the amino acid sequence of SEQ ID NO: 4; (c) CDR-H3 containing the amino acid sequence of SEQ ID NO: 5; (d) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6; (e) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7; and (f) CDR-L3 containing the amino acid sequence of SEQ ID NO: 8.

[0056] In another embodiment, the Disclosure provides an anti-TL1A antibody for use in the treatment of a patient's IBD, wherein an effective amount of the anti-TL1A antibody is administered to the patient in a dosing regimen including an induction phase, the induction phase comprising only four doses of the anti-TL1A antibody, (i) the second dose of the anti-TL1A antibody is administered approximately two weeks after the first dose; (ii) the third dose of the anti-TL1A antibody is administered approximately four weeks after the second dose; and (iii) the fourth dose of the anti-TL1A antibody is administered approximately four weeks after the third dose, wherein the anti-TL1A antibody comprises (a) a heavy chain having at least 95% sequence identity with SEQ ID NO: 9 or having the amino acid sequence of SEQ ID NO: 9; and (b) a light chain having at least 95% sequence identity with SEQ ID NO: 10 or having the amino acid sequence of SEQ ID NO: 10.

[0057] In another embodiment, the Disclosure provides an anti-TL1A antibody for use in the treatment of a patient's IBD, wherein an effective amount of the anti-TL1A antibody is administered to the patient in a dosing regimen including an induction phase and a maintenance phase, (a) the induction phase comprising only four doses of the anti-TL1A antibody, (i) the second dose of the anti-TL1A antibody being administered approximately two weeks after the first dose; (ii) the third dose of the anti-TL1A antibody being administered approximately four weeks after the second dose; and (iii) the fourth dose of the anti-TL1A antibody being administered approximately four weeks after the third dose; and (b) the maintenance phase comprising four-week doses of the anti-TL1A antibody, wherein the anti-TL1A antibody comprises (a) a heavy chain having at least 95% sequence identity with SEQ ID NO: 9 or having the amino acid sequence of SEQ ID NO: 9; and (b) a light chain having at least 95% sequence identity with SEQ ID NO: 10 or having the amino acid sequence of SEQ ID NO: 10.

[0058] In another aspect, the Disclosure provides the use of an anti-TL1A antibody in the manufacture of a pharmaceutical for treating a patient's IBD, wherein an effective amount of the anti-TL1A antibody is administered to the patient in a dosing regimen including an induction phase, the induction phase comprising only four doses of the anti-TL1A antibody, (i) the second dose of the anti-TL1A antibody is administered approximately two weeks after the first dose; (ii) the third dose of the anti-TL1A antibody is administered approximately four weeks after the second dose; and (iii) the anti-TL1A antibody The fourth dose of the body will be administered approximately four weeks after the third dose; the anti-TL1A antibody will contain the following complementarity-determining regions (CDRs): (a) CDR-H1 containing the amino acid sequence of SEQ ID NO: 3; (b) CDR-H2 containing the amino acid sequence of SEQ ID NO: 4; (c) CDR-H3 containing the amino acid sequence of SEQ ID NO: 5; (d) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6; (e) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7; and (f) CDR-L3 containing the amino acid sequence of SEQ ID NO: 8.

[0059] In another aspect, the Disclosure provides the use of an anti-TL1A antibody in the manufacture of a pharmaceutical for treating a patient's IBD, wherein an effective amount of the anti-TL1A antibody is administered to the patient in a dosing regimen including an induction phase and a maintenance phase, (a) the induction phase comprising only four doses of the anti-TL1A antibody, (i) the second dose of the anti-TL1A antibody being administered approximately two weeks after the first dose; (ii) the third dose of the anti-TL1A antibody being administered approximately four weeks after the second dose; and (iii) the fourth dose of the anti-TL1A antibody The administration of the drug will be performed approximately four weeks after the third dose; (b) the maintenance phase will consist of administration of anti-TL1A antibodies every four weeks, the anti-TL1A antibodies including the following CDRs: (a) CDR-H1 containing the amino acid sequence of SEQ ID NO: 3; (b) CDR-H2 containing the amino acid sequence of SEQ ID NO: 4; (c) CDR-H3 containing the amino acid sequence of SEQ ID NO: 5; (d) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6; (e) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7; and (f) CDR-L3 containing the amino acid sequence of SEQ ID NO: 8.

[0060] In another aspect, the Disclosure provides the use of an anti-TL1A antibody in the manufacture of a pharmaceutical for treating UC in a patient, wherein an effective amount of anti-TL1A antibody is administered to the patient in a dosing regimen including an induction phase and a maintenance phase, (a) the induction phase comprising only four intravenous doses of anti-TL1A antibody in doses of approximately 500 mg each, (i) the second dose of anti-TL1A antibody being administered approximately two weeks after the first dose; (ii) the third dose of anti-TL1A antibody being administered approximately four weeks after the second dose; and (iii) the fourth dose of anti-TL1A antibody The administration of the drug will be performed approximately four weeks after the third dose; (b) the maintenance phase will consist of subcutaneous administration of anti-TL1A antibody at a dose of approximately 450 mg every four weeks, the anti-TL1A antibody including the following CDRs: (a) CDR-H1 containing the amino acid sequence of SEQ ID NO: 3; (b) CDR-H2 containing the amino acid sequence of SEQ ID NO: 4; (c) CDR-H3 containing the amino acid sequence of SEQ ID NO: 5; (d) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6; (e) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7; and (f) CDR-L3 containing the amino acid sequence of SEQ ID NO: 8.

[0061] In another aspect, the Disclosure provides the use of an anti-TL1A antibody in the manufacture of a pharmaceutical for treating a patient's CD, wherein an effective amount of anti-TL1A antibody is administered to the patient in a dosing regimen including an induction phase and a maintenance phase, (a) the induction phase comprising only four intravenous doses of anti-TL1A antibody at doses of approximately 500 mg each, (i) the second dose of anti-TL1A antibody being administered approximately two weeks after the first dose; (ii) the third dose of anti-TL1A antibody being administered approximately four weeks after the second dose; and (iii) the fourth dose of anti-TL1A antibody The administration of the drug will be performed approximately four weeks after the third dose; (b) the maintenance phase will consist of subcutaneous administration of anti-TL1A antibody at a dose of approximately 450 mg every four weeks, the anti-TL1A antibody including the following CDRs: (a) CDR-H1 containing the amino acid sequence of SEQ ID NO: 3; (b) CDR-H2 containing the amino acid sequence of SEQ ID NO: 4; (c) CDR-H3 containing the amino acid sequence of SEQ ID NO: 5; (d) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6; (e) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7; and (f) CDR-L3 containing the amino acid sequence of SEQ ID NO: 8.

[0062] In another aspect, the Disclosure provides the use of an anti-TL1A antibody in the manufacture of a pharmaceutical for treating a patient's CD, wherein an effective amount of anti-TL1A antibody is administered to the patient in a dosing regimen including an induction phase and a maintenance phase, (a) the induction phase comprising only four intravenous doses of anti-TL1A antibody at a dose of approximately 500 mg each, (i) the second dose of anti-TL1A antibody being administered approximately two weeks after the first dose; (ii) the third dose of anti-TL1A antibody being administered approximately four weeks after the second dose; and (iii) the fourth dose of anti-TL1A antibody The administration will be performed approximately four weeks after the third dose; (b) the maintenance phase will consist of subcutaneous administration of approximately 150 mg of anti-TL1A antibody every four weeks, the anti-TL1A antibody including the following CDRs: (a) CDR-H1 containing the amino acid sequence of SEQ ID NO: 3; (b) CDR-H2 containing the amino acid sequence of SEQ ID NO: 4; (c) CDR-H3 containing the amino acid sequence of SEQ ID NO: 5; (d) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6; (e) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7; and (f) CDR-L3 containing the amino acid sequence of SEQ ID NO: 8.

[0063] In another aspect, the Disclosure provides the use of an anti-TL1A antibody in the manufacture of a pharmaceutical for treating a patient's IBD, wherein an effective amount of the anti-TL1A antibody is administered to the patient in a dosing regimen including an induction phase, the induction phase comprising only four doses of the anti-TL1A antibody, wherein (i) the second dose of the anti-TL1A antibody is administered approximately two weeks after the first dose; (ii) the third dose of the anti-TL1A antibody is administered approximately four weeks after the second dose; and (iii) the fourth dose of the anti-TL1A antibody is administered approximately four weeks after the third dose, wherein the anti-TL1A antibody comprises (a) a heavy chain having at least 95% sequence identity with SEQ ID NO: 9 or having the amino acid sequence of SEQ ID NO: 9; and (b) a light chain having at least 95% sequence identity with SEQ ID NO: 10 or having the amino acid sequence of SEQ ID NO: 10.

[0064] In another aspect, the Disclosure provides the use of an anti-TL1A antibody in the manufacture of a pharmaceutical for treating a patient's IBD, wherein an effective amount of anti-TL1A antibody is administered to the patient in a dosing regimen including an induction phase and a maintenance phase, (a) the induction phase comprising only four doses of anti-TL1A antibody, (i) the second dose of anti-TL1A antibody being administered approximately two weeks after the first dose; (ii) the third dose of anti-TL1A antibody being administered approximately four weeks after the second dose; and (iii) the fourth dose of anti-TL1A antibody being administered approximately four weeks after the third dose; and (b) the maintenance phase comprising four-week doses of anti-TL1A antibody, wherein the anti-TL1A antibody comprises (a) a heavy chain having at least 95% sequence identity with SEQ ID NO: 9 or having an amino acid sequence of SEQ ID NO: 9; and (b) a light chain having at least 95% sequence identity with SEQ ID NO: 10 or having an amino acid sequence of SEQ ID NO: 10. [Brief explanation of the drawing]

[0065] [Figure 1] This is a schematic diagram showing the design of the GA45329 study. IV = intravenous; SC = subcutaneous; BL = baseline; D = day; OLE = open-label extension; W = week; Q2W = every 2 weeks; Q4W = every 4 weeks; R = randomization. [Figure 2A] This is a schematic diagram showing the design of the open-label extension phase of the GA45329 study. DW = disease worsening; DWC = disease worsening criteria; OLE = open-label extension; W = week; Q2W = every 2 weeks; Q4W = every 4 weeks. [Figure 2B] This is a schematic diagram showing the design of the open-label extension phase of the GA45330 study. DW = disease worsening; DWC = disease worsening criteria; W12 = week 12; Q2W = every 2 weeks; Q4W = every 4 weeks. [Figure 3] This is a schematic diagram showing the design of the GA45330 study. IV = intravenous; SC = subcutaneous; BL = baseline; D = day; OLE = open-label extension; W = week; Q2W = every 2 weeks; Q4W = every 4 weeks; R = randomization. [Figure 4]This is a schematic diagram showing the design of the GA45331 study. IV = intravenous; SC = subcutaneous; BL = baseline; D = day; OLE = open-label extension; W = week; Q2W = every 2 weeks; Q4W = every 4 weeks; R = randomization. [Figure 5] This is a schematic diagram showing the design of the GA45332 study. IV = intravenous; SC = subcutaneous; BL = baseline; D = day; OLE = open-label extension; W = week; Q2W = every 2 weeks; Q4W = every 4 weeks; R = randomization. [Figure 6] This is a schematic diagram showing the design of the open-label extension (OLE) phase of the GA45331 study. DW = disease worsening; DWC = disease worsening criteria; SC = subcutaneous; W = weeks. [Figure 7] This is a schematic diagram showing the design of the open-label extension (OLE) phase of the GA45332 study. DW = disease worsening; DWC = disease worsening criteria; SC = subcutaneous; W = weeks. [Figure 8] This is a schematic diagram comparing the Phase 3 GA45329 (ulcerative colitis (UC)) and GA45331 (Crohn's disease (CD)) studies with the Phase 2a (TUSCANY) and Phase 2b (TUSCANY-2) clinical trials. It shows the cumulative bioavailable dose (mg) over 12 weeks. IV = intravenous; SC = subcutaneous; OL = open-label; Q4W = every 4 weeks; fu = follow-up; mo = monthly. [Figure 9] This is a set of graphs showing the total pharmacokinetics (PK) (total serum drug concentration (μg / mL)) of afimkibart over time for the induction regimen of the Phase 2a (TUSCANY) clinical trial (Ph2a(UC)), the 450 mg induction regimen of the Phase 2b (TUSCANY-2) clinical trial (Ph2B(UC)), and two induction regimens of the Phase 3 clinical trial provided herein. 4×IV: afimkibart is administered intravenously (IV) a total of four times at weeks 0, 2, 6, and 10 of the 12-week regimen. 5×IV: afimkibart is administered IV a total of five times at weeks 0, 2, 4, 6, and 10 of the 12-week regimen. The Phase 2a and Phase 2b plots represent actual data. The Phase 3 plots are modeled. In the modeled panel, the solid line represents the median drug concentration, and the dotted line represents the 90% confidence interval (CI). [Figure 10] This is a set of graphs showing the levels of soluble TL1A (sTL1A) (pg / mL) over time for the induction regimen of the Phase 2a (TUSCANY) clinical trial (Ph2a), the 450 mg induction regimen of the Phase 2b (TUSCANY-2) clinical trial (Ph2B), and two induction regimens of the Phase 3 clinical trial provided herein. 4×IV: afimkibart is administered intravenously (IV) a total of four times at weeks 0, 2, 6, and 10 of the 12-week regimen. 5×IV: afimkibart is administered IV a total of five times at weeks 0, 2, 4, 6, and 10 of the 12-week regimen. The Phase 2a and Phase 2b plots represent actual data. The Phase 3 plots are modeled. [Modes for carrying out the invention]

[0066] Detailed description of the invention The present invention provides therapeutic methods and compositions for treating inflammatory bowel diseases, such as ulcerative colitis (UC) and Crohn's disease (e.g., moderate to severe active UC and CD). The present invention is at least in part based on the discovery that immunotherapy comprising an anti-TL1A antibody may be useful in treating IBD. Compositions, uses, and kits comprising such antibodies are also provided herein.

[0067] UC is a chronic gastrointestinal inflammatory disorder characterized by diffuse mucosal inflammation involving the rectum with continuous extension into the colon. While many risk factors are associated with the development of UC, the disease essentially represents a dysregulation of the mucosal immune system between genetically susceptible individuals in response to the symbiotic microbiome and other environmental triggers.

[0068] The burden of ulcerative colitis is increasing, and global incidence and prevalence have been rising over time (Ungaro et al., Lancet, 389:1756-1770, 2017; Kaplan et al., Nat Rev Gastroenterol Hepatol, 18:56-66, 2021; Lewis et al., Gastroenterology, 165:1197-1205, 2023). The disease can affect people of any age, but the peak age of onset is between 15 and 30 years old, with a second peak between 50 and 70 years old (Ordas et al., Lancet, 380:1606-1619, 2012).

[0069] According to recent STRIDE-II guidelines, the short-term goal most valued by patients is symptom relief. Long-term treatment goals include clinical remission, endoscopic cure, restoration of quality of life, and absence of disability (Turner et al., Gastroenterology, 160:1570-1583, 2021).

[0070] Drug therapies, including inhibition of pro-inflammatory cytokines and adhesion molecules, have been shown to provide therapeutic benefits, but there are still upper limits, with UC remission rates in induction trials being approximately 20%–30% (Alsoud et al., Lancet Gastroenterol Hepatol, 6:589-595, 2021).

[0071] Recent estimates of remission rates from international studies are 37%–55% with current treatments; however, 22%–29% of patients experience a loss of response to current medications (i.e., anti-TNF therapy, anti-integrin, JAK inhibitor, or anti-IL-12 / 23), highlighting the need for more lasting treatment options for UC patients (Rubin et al., Inflamm Bowel Dis, 27:1942–1953, 2021).

[0072] The advanced treatments available are associated with various risks or adverse drug reactions, including serious infections, cardiovascular events, thrombosis, and malignancies (Bhat et al., Inflamm Bowel Dis, 30(5):829-843, 2023). These safety considerations must be balanced with patient-specific factors, and such considerations may exclude some treatment options for individual patients.

[0073] Colectomy is required in up to 20-30% of UC patients with uncontrolled, progressive inflammation that is refractory to drug therapy. While this is an appropriate treatment strategy for these patients, these colorectal surgical procedures are also associated with early and late complications (Peyrin-Biroulet et al., Aliment Pharmacol Ther, 44:807-816, 2016; Fradet et al., Int J Surg Open, 22:22-32, 2020). These data indicate that there is a need for more robust, well-tolerated treatments with sustained efficacy for UC patients whose quality of life is significantly affected.

[0074] Crohn's disease (CD) is a chronic, progressive inflammatory disease of the gastrointestinal tract characterized by periods of relapse and remission, which can ultimately lead to bowel damage and impairment. While most patients present with an inflammatory phenotype, over time, uncontrolled inflammation can lead to complications such as fibrous strictures, fistula formation, or intestinal neoplasms. Half of all CD patients develop bowel complications within 20 years of diagnosis, requiring surgical intervention.

[0075] The current goals of C. difficile (CD) treatment are to induce and maintain clinical and endoscopic remission, halt disease progression, and prevent long-term complications. Currently available therapies, including advanced treatments such as corticosteroids, immunosuppressants, and biological agents, are effective in many patients; however, long-term efficacy rates remain unsatisfactory, with up to 30% of patients showing no initial response to treatment and up to 50% losing their response over time. Furthermore, currently available advanced treatments are associated with various risks or adverse drug reactions, including serious infections, cardiovascular events, thrombosis, and malignancies.

[0076] Despite available treatments, disease progression and complications mean that an estimated 50%–80% of CD patients will require surgery in their lifetime. While timely surgery is appropriate to avoid complications, surgery is not curative and carries the risk of postoperative complications with associated mortality risks. Furthermore, postoperative recurrence is common depending on the patient's risk factors, with approximately 50% of patients experiencing endoscopic recurrence within one year of ileocolectomy. Repeated surgical procedures can lead to short bowel syndrome, accompanied by chronic malabsorption and potential dependence on total parenteral nutrition. Therefore, there is an unmet need for safer and more effective treatments for CD.

[0077] I. Definition The aspects and embodiments of the present invention described herein are understood to include "a," "consisting of," and "essentially consisting of." As used herein, the singular forms "a," "an," and "the" include plural references unless otherwise indicated.

[0078] As used herein, the term “about” refers to the normal range of error for each value, as readily understood by those skilled in the art. References of “about” a value or parameter in this specification include (and describe) aspects directed toward the value or parameter itself. For example, a description referring to “about X” includes a description of “X.”

[0079] As used herein, the term “induction phase” refers to a series of one or more administrations or drug cycles (e.g., approximately 2 to 6 administrations or drug cycles) of one or more therapeutic agents (e.g., anti-TL1A antibodies (e.g., afimkibart)) administered to a subject, optionally followed by a maintenance phase.

[0080] As used herein, the term “maintenance phase” refers to a series of one or more administrations or dosing cycles of one or more therapeutic agents (e.g., anti-TL1A antibodies (e.g., afimkibart)) administered to a subject after the induction phase without the intervention of any related surgery (i.e., without any interventional surgery related to the disease or condition that is intended to be treated by one or more therapeutic agents). In some cases, the maintenance phase is initiated only if the subject has not experienced disease progression or unacceptable toxicity during the induction phase. The induction and maintenance phases may or may not involve the use of the same therapeutic agent.

[0081] As used herein, "afimkibart" (also known as RO7790121, RVT-3101, or PF-06480605) is an antibody that binds to the tumor necrosis factor (TNF) superfamily protein TNF-like 1A (TL1A) and contains the heavy chain sequence of SEQ ID NO: 9 and the light chain sequence of SEQ ID NO: 10.

[0082] The terms “antibody that binds to TL1A” and “anti-TL1A antibody” refer to an antibody that can bind to TL1A with sufficient affinity so that it is useful as a diagnostic and / or therapeutic agent in targeting TL1A. In one embodiment, the degree of binding of an anti-TL1A antibody to unrelated non-TL1A proteins is less than about 10% of the antibody’s binding to TL1A, as measured, for example, by surface plasmon resonance (SPR). In one embodiment, an antibody that binds to TL1A has a viscosity of ≤1 μM, ≤100 nM, ≤10 nM, ≤1 nM, ≤0.1 nM, ≤0.01 nM, or ≤0.001 nM (e.g., 10 -8 M or less, for example, 10 -8 M~10 -13 M, for example 10 -9M~10 -13 The dissociation constant (K) of M D The term "antibody" encompasses a variety of antibody structures that exhibit desired antigen-binding activity, including but not limited to monoclonal antibodies, multispecific antibodies (e.g., bispecific antibodies), and antibody fragments.

[0083] As used herein, the term “monoclonal antibody” refers to an antibody obtained from a substantially homogeneous population of antibodies, i.e., the antibodies forming this population are essentially identical except for post-translational modifications that may occur, for example, during manufacturing and / or storage. These antibodies are against the same epitope (or, in the case of multispecific monoclonal antibodies, the same group of epitopes, e.g., in the case of bispecific monoclonal antibodies, the same pair of epitopes). This definition explicitly excludes polyclonal antibody preparations, which are mixtures of antibodies against different epitopes. Monoclonal antibodies according to the present invention can be produced by a variety of techniques, including, but not limited to, hybridoma methodologies, recombinant DNA methods, phage display methods, and methods utilizing transgenic animals containing all or part of a human immunoglobulin locus, including, but not limited to, such methods and other exemplary methods for producing monoclonal antibodies described herein.

[0084] The term "full-length antibody" refers to an antibody having an immunoglobulin structure comprising two light chains and two heavy chains, and including an Fc region as defined herein. In one embodiment, the antibody is a full-length IgG1 antibody.

[0085] A "human antibody" is an antibody produced by a human or human cell, or an antibody that has an amino acid sequence corresponding to a non-human antibody that utilizes a sequence encoding a human antibody, such as the human antibody repertoire. This definition of a human antibody explicitly excludes humanized antibodies that contain non-human antigen-binding residues.

[0086] A “humanized” antibody refers to an antibody that contains amino acid residues from a non-human CDR and amino acid residues from a human FR. In one embodiment, the humanized antibody substantially contains all of at least one, typically two, variable domains, in which all or substantially all of the CDRs correspond to the CDRs of a non-human antibody and all or substantially all of the FRs correspond to the FRs of a human antibody. The humanized antibody may optionally contain at least a portion of the antibody constant region derived from a human antibody. The “humanized form” of an antibody, e.g., a non-human antibody, refers to an antibody that has undergone humanization.

[0087] "Native antibodies" refer to naturally occurring immunoglobulin molecules with various structures. For example, a native IgG antibody is a heterotetrameric glycoprotein with approximately 150,000 daltons, composed of two identical light chains (LCs) and two identical heavy chains (HCs) linked by disulfide bonds. From the N-terminus to the C-terminus, each heavy chain has a variable heavy chain domain (VH), also called a variable heavy chain domain or heavy chain variable region, followed by three constant heavy chain domains (CH1, CH2, and CH3). Similarly, from the N-terminus to the C-terminus, each light chain has a variable light chain domain (VL), also called a variable light chain domain or light chain variable region, followed by a constant light chain domain (CL).

[0088] An "antibody fragment" refers to a molecule other than a full-length antibody, including a portion of a full-length antibody that binds to the antigen to which the full-length antibody binds. Examples of antibody fragments include, but are not limited to, Fv molecules, Fab molecules, Fab' molecules, Fab'-SH molecules, F(ab')2 molecules, diabodies, linear antibody molecules, single-chain antibody molecules (e.g., scFv and scFab molecules), and multispecific (e.g., bispecific) antibodies formed from antibody fragments.

[0089] A "variable region" or "variable domain" is a domain in the heavy or light chain of an antibody that is involved in the binding of the antibody to the antigen. The variable domains of the heavy and light chains of native antibodies (VH and VL, respectively) generally have similar structures, and each domain contains four conserved framework regions (FRs) and three complementarity-determining regions (CDRs). (e.g., Kindt et al. Kuby Immunology, 6) th See ed., WH Freeman and Co., page 91 (2007). A single VH or VL domain may be sufficient to confer antigen-binding specificity. Furthermore, antibodies that bind to a specific antigen may be isolated by screening a library of complementary VL or VH domains using the VH or VL domain of the antibody that binds to the antigen, respectively. See, for example, Portolano et al., J. Immunol. 150:880-887 (1993); Clarkson et al., Nature 352:624-628 (1991).

[0090] The N-terminal glutamine or glutamic acid residue of the heavy or light chain of an antibody can be spontaneously converted to pyroglutamic acid (see, for example, Liu et al., Journal of Pharmaceutical Sciences 97, 2426-2447 (2008), Rehder et al., Journal of Chromatography A 1102, 164-175 (2006), Chelius et al., Anal Chem 78, 2370-2376 (2006)). Therefore, variable domains disclosed herein that include either a glutamine (Q) or glutamic acid (E) amino acid residue at the N-terminus of the heavy or light chain of an antibody may include an N-terminal pyroglutamic acid (pyro-E) residue instead of the N-terminal Q or E residue. Similarly, the heavy or light chains of antibodies disclosed herein that contain either a glutamine (Q) or glutamic acid (E) amino acid residue at the N-terminus may contain a pyroglutamic acid (pyro-E) residue at the N-terminus instead of the Q or E residue. Therefore, for each antibody heavy chain, light chain, or variable domain sequence disclosed herein that contains an N-terminus Q or E residue, the corresponding sequence having a pyro-E residue at the N-terminus is also included.

[0091] The "Human Consensus Framework" is a framework representing the most commonly occurring amino acid residues in the selection of human immunoglobulin VL or VH framework sequences. Generally, the selection of human immunoglobulin VL or VH sequences derives from subgroups of variable domain sequences. Generally, the sequence subgroups are those found in Kabat, EA, et al., Sequences of Proteins of Immunological Interest, 5th ed., Public Health Service, National Institutes of Health, Bethesda, MD (1991) NIH Publication 91-3242 (hereinafter, "Kabat1991"). In one embodiment, for VL, the subgroup is subgroup Kappa I as found in Kabat1991. In one embodiment, for VH, the subgroup is subgroup III as found in Kabat1991.

[0092] As used herein, the terms “complementarity-determining regions” or “CDRs” refer to each region of the antibody variable domain whose sequence is hypervariable and which determines antigen-binding specificity. Generally, antibodies contain six CDRs, three located in the VH (CDR-H1, CDR-H2, CDR-H3) and three located in the VL (CDR-L1, CDR-L2, CDR-L3). CDRs are defined by various methods / systems by those skilled in the art. These systems and / or definitions have been developed and refined over the years and include Kabat, Chothia, IMGT, AbM, and Contact. The Kabat definition is based on sequence variability and is generally the most commonly used. The Chothia definition is based on the location of the structural loop region. The IMGT system is based on sequence variability and location within the structure of the variable domain. The AbM definition is a compromise between Kabat and Chothia. The Contact definition is based on the analysis of available antibody crystal structures. Software programs (e.g., abYsis: http: / / www.abysis.org / abysis / sequence_input / key_annotation / key_annotation.cgi) are available and publicly known to those skilled in the art for the analysis of antibody sequences and determination of CDRs.

[0093] The exemplary CDRs used herein include the following (amino acid residue numbering by cited reference, i.e., Chothia numbering for Chothia and Contact definitions, Kabat numbering for Kabat definitions, and IMGT numbering for IMGT definitions): (a) Hypervariable loops occurring at amino acid residues 26-32 (L1), 50-52 (L2), 91-96 (L3), 26-32 (H1), 53-55 (H2), and 96-101 (H3) (according to Chothia and Lesk, J. Mol. Biol. 196:901-917 (1987) ("Chothia definition")); (b) CDRs occurring at amino acid residues 24-34 (L1), 50-56 (L2), 89-97 (L3), 31-35B (H1), 50-65 (H2), and 95-102 (H3) (according to Kabat 1991 ("Kabat definition"); (c) Antigen contact occurring at amino acid residues 30-36 (L1), 46-55 (L2), 89-96 (L3), 30-35 (H1), 47-58 (H2), and 93-101 (H3) (according to MacCallum et al. J. Mol. Biol. 262:732-745 (1996) ("Contact definition")); and (d) CDRs occurring at amino acid residues 27-38 (L1), 56-65 (L2), 105-117 (L3), 27-38 (H1), 56-65 (H2), and 105-117 (H3) (according to Lefranc et al. Dev. Comp. Immunol. 27:55-77 (2003) ("IMGT definition")).

[0094] The "framework" or "FR" refers to variable domain residues other than the complementarity-determining region (CDR). The variable domain FR generally consists of four FR domains: FR1, FR2, FR3, and FR4. Therefore, the CDR and FR sequences generally appear in VH (or VL) in the following sequence: FR1-CDR-H1(CDR-L1)-FR2-CDR-H2(CDR-L2)-FR3-CDR-H3(CDR-L3)-FR4.

[0095] The "class" of an antibody refers to the type of constant domain or constant region held by its heavy chain. Antibodies exist in five main classes: IgA, IgD, IgE, IgG, and IgM, some of which can be further divided into "subclasses" (isotypes), such as IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2. The heavy chain constant domains corresponding to different classes of immunoglobulins are called α, δ, ε, γ, and μ, respectively. The light chain of an antibody can be assigned to one of two types based on the amino acid sequence of its constant domain, called kappa (κ) and lambda (λ).

[0096] As used herein, the terms “human-derived constant region” or “human constant region” refer to the constant region of a human antibody, particularly the heavy chain constant region and / or light chain kappa or lambda constant region of a human antibody of subclass IgG1, IgG2, IgG3, or IgG4. Such constant regions are well known in the latest art and are described, for example, by Kabat 1991. Unless otherwise specified herein, the numbering of amino acid residues in the constant regions follows the numbering system described in Kabat 1991. Specifically, the Kabat numbering system (hereinafter referred to as “Kabat numbering” or “Kabat numbering”; see pages 647–660 of Kabat 1991) is used for the light chain constant domains of kappa and lambda isotypes, and the Kabat EU index numbering system (hereinafter referred to as “Kabat EU index numbering” or “Kabat EU index numbering”; see pages 661–723 of Kabat 1991) is used for the heavy chain constant domains.

[0097] The term “Fc region” is used herein to define the C-terminal region of an immunoglobulin heavy chain that includes at least a portion of the constant region. This term includes native sequence Fc regions and variant Fc regions. In one embodiment, the human IgG heavy chain Fc region extends from Cys226 or Pro230 to the carboxyl terminus of the heavy chain. However, antibodies produced by host cells may undergo post-translational cleavage of one or more amino acids from the C-terminus of the heavy chain, particularly one or two amino acids. Thus, by expression of certain nucleic acid molecules encoding a full-length heavy chain, antibodies produced by host cells may contain the full-length heavy chain or a cleaved variant of the full-length heavy chain. This is particularly true when the last two C-terminal amino acids of the heavy chain are glycine (G446) and lysine (K447, Kabat EU numbering). Therefore, the C-terminal lysine (Lys447) or C-terminal glycine (Gly446) and lysine (Lys447) of the Fc region may or may not be present. Unless otherwise indicated, the amino acid sequences of heavy chains containing the Fc region are shown herein without the C-terminal lysine. However, corresponding sequences containing the C-terminal lysine residue are also included. Thus, in one embodiment, the heavy chain containing the Fc region specified herein includes an additional C-terminal lysine residue (K447, Kabat EU numbering). Corresponding sequences without a C-terminal glycine residue are also included. Thus, in one embodiment, the heavy chain containing the Fc region identified herein lacks the C-terminal glycine residue (G446, Kabat EU numbering). In such a heavy chain, the C-terminal amino acid residue may be proline (P445, Kabat EU numbering) or prolineamide (P445-NH2, Kabat EU numbering). Unless otherwise specified herein, the numbering of amino acid residues in the Fc region or heavy chain constant region follows the EU numbering system, also known as the EU index, as described in Kabat 1991.

[0098] "Effector function" refers to the biological activity resulting from the Fc region of an antibody, which varies depending on the antibody isotype. Examples of antibody effector functions include C1q binding, complement-dependent cell-mediated cytotoxicity (CDC), Fc receptor binding, antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cell phagocytosis (ADCP), downregulation of cell surface receptors (e.g., B cell receptors), and B cell activation.

[0099] "Affinity" refers to the sum of the non-covalent interactions between a single binding site of a molecule (e.g., an antibody) and its binding partner (e.g., an antigen). Unless otherwise indicated, as used herein, "binding affinity" refers to the intrinsic binding affinity that reflects the 1:1 interaction between the binding pair's parts (e.g., antibody and antigen). The affinity of molecule X for its partner Y can generally be expressed by its dissociation constant (KD). Affinity can be measured by methods common in the art, including those described herein. A preferred method for measuring affinity is surface plasmon resonance (SPR).

[0100] An "isolated" antibody is one that has been separated from its natural environment. In some embodiments, antibodies are purified to a purity of 95% or more than 99%, as determined by methods such as electrophoresis (e.g., SDS-PAGE, isoelectric focusing (IEF), capillary electrophoresis) or chromatography (e.g., ion exchange or reverse-phase HPLC, affinity chromatography, size exclusion chromatography). For a review of methods for evaluating antibody purity, see, for example, Flatman et al., J.Chromatogr.B 848:79-87 (2007).

[0101] "Isolated" nucleic acids are nucleic acid molecules that have been separated from their natural environment. Isolated nucleic acids include nucleic acid molecules that are normally contained within cells, but these nucleic acid molecules exist outside of chromosomes or at chromosomal locations different from their natural chromosomal locations.

[0102] "Antibody-encoding isolated nucleic acid" refers to one or more nucleic acid molecules encoding antibody heavy and light chains (or fragments thereof), and includes nucleic acid molecules(s) in a single vector or separate vectors, such nucleic acid molecules(s) located at one or more locations within a host cell.

[0103] As used herein, the term "vector" refers to a nucleic acid molecule capable of replicating another nucleic acid it is linked to. This term includes not only vectors as self-replicating nucleic acid structures, but also vectors integrated into the genome of a host cell into which they are introduced. Certain vectors can direct the expression of a operably linked nucleic acid. Such vectors are referred to herein as "expression vectors."

[0104] The terms “host cell,” “host cell line,” and “host cell culture” are used interchangeably and refer to cells into which exogenous nucleic acids have been introduced, including the offspring of such cells. Host cells include “transformers” and “transformed cells,” and these cells include primary transformed cells and their offspring, regardless of passage number. Offspring may not be completely identical to the parent cells in terms of nucleic acid content, but may include mutations. Mutant offspring having the same function or biological activity as those screened or selected in the original transformed cells are included herein. Suitable host cells may include, for example, prokaryotic cells such as CHO cells, HEK-293 cells, Expi293F cells, PER.C6 cells, NSO cells, lymphocytic cells, and Escherichia coli, as well as other eukaryotic hosts such as plant cells and fungi. Human host cells are included on the condition that they are not used in the human body.

[0105] A "naked antibody" refers to an antibody that is not conjugated to a heterogeneous site (e.g., a cytotoxic site) or a radioactive label. Naked antibodies may be present in a pharmaceutical composition.

[0106] The "amino acid sequence identity percentage (%)" relative to a reference polypeptide sequence is defined as the percentage of amino acid residues in a candidate sequence that are identical to amino acid residues in the reference polypeptide sequence, after aligning the sequences and introducing gaps if necessary to achieve the maximum sequence identity percentage, and without considering any conservative substitutions as part of the sequence identity for the purpose of alignment. Alignment for determining the amino acid sequence identity percentage can be achieved in various ways within the scope of the art, for example, using publicly available computer software such as BLAST, BLAST-2, Clustal W, MegAlign (DNASTAR) software, or FASTA program packages. Those skilled in the art can determine appropriate parameters for sequence alignment, including any algorithm necessary to achieve the maximum alignment over the full length of the sequences being compared. Alternatively, the identity percentage value can be generated using the sequence comparison computer program ALIGN-2. The ALIGN-2 sequence comparison computer program was created by Genentech, Inc., and its source code is filed in the user documentation of the US Copyright Office (Washington DC, 20559), registered under US Copyright Registration No. TXU510087, and published in International Publication No. 2001 / 007611.

[0107] Unless otherwise specified, for the purposes of this specification, amino acid sequence identity percentage values ​​are generated using the ggsearch program in FASTA package version 36.3.8c, or the subsequent BLOSUM50 comparison matrix. The FASTA program package is described by WRPearson and DJLipman (1988), "Improved Tools for Biological Sequence Analysis" Proc.Nat.Acad.Sci.85:2444-2448; WRPearson (1996), "Effective protein sequence comparison" Meth.Enzymol.266:227-258; and Pearson et al. (1997) Genomics 46:24-36, and is publicly available at www.fasta.bioch.virginia.edu / fasta_www2 / fasta_down.shtml or www.ebi.ac.uk / Tools / sss / fasta. Alternatively, you can use the ggsearch(global protein:protein) program with default options (BLOSUM50;open:-10;ext:-2;Ktup=2) to compare sequences using a public server accessible at fasta.bioch.virginia.edu / fasta_www2 / index.cgi, ensuring that a global rather than local alignment is performed. The amino acid identity percentage is shown in the output alignment header.

[0108] An "immune conjugate" is an antibody conjugated to one or more heterologous molecules, including but not limited to one or more cytotoxic agents.

[0109] As used herein, the term “treatment” refers to a clinical intervention in an attempt to alter the natural course of a disease in the course of clinicopathology. Desired effects of treatment include a reduction in the rate of disease progression, recovery or mitigation of the disease state, and remission or improvement of prognosis. For the purposes of this disclosure, beneficial or desired clinical outcomes include, for example, a reduction or improvement in the signs and symptoms of inflammatory bowel disease (IBD) (e.g., ulcerative colitis (UC) or Crohn's disease (CD)) compared to before administration of an anti-TL1A antibody.

[0110] The “effective dose” of a drug, such as a pharmaceutical composition, refers to the amount of antibody or drug that is effective in the dosage and duration required to achieve the desired treatment as defined above. In more specific embodiments, the effective dose prevents, alleviates or reverses the signs or symptoms of IBD and / or extends the survival of the subject being treated. Beneficial or desired outcomes for prophylactic use include the elimination or reduction of risk, reduction of severity, or delay of the onset of the disease, including the biochemical, histological and / or behavioral symptoms of the disease, its complications, and intermediate pathological phenotypes that appear during the onset of the disease. For therapeutic use, beneficial or desired outcomes include clinical outcomes such as the reduction of one or more signs or symptoms of IBD, a reduction in the dosage of other medications required to treat the disease, an enhancement of the effect of another medication, and / or delay of disease progression in the patient. The effective dose may be administered in one or more doses. For the purposes of this disclosure, the effective dose of a drug, compound, or pharmaceutical composition is sufficient to achieve a prophylactic or therapeutic treatment, directly or indirectly. As understood in the clinical field, the effective dose of a drug, compound, or pharmaceutical composition may or may not be achieved in combination with other drugs, compounds, or pharmaceutical compositions. Therefore, the “effective dose” may be considered in relation to the administration of one or more therapeutic agents, and a monotherapy agent may be considered effective if, in combination with one or more other agents, the desired outcome can or would be achieved.

[0111] In this specification, “effective dose” may refer to the amount of a therapeutic agent (e.g., an anti-TL1A antibody (e.g., afimkibart)) or a combination of therapeutic agents (e.g., an anti-TL1A antibody and one or more additional therapeutic agents)) that achieves a therapeutic outcome. In some examples, the effective dose of a therapeutic agent or combination of therapeutic agents is the amount of an agent or combination of agents that achieves the clinical endpoint of clinical remission, clinical response (e.g., improved modified Mayo score (mMS) or partially modified Mayo score (pmMS)), endoscopic improvement, endoscopic remission, histological endoscopic mucosal improvement, histological endoscopic remission, and / or remission without corticosteroids. Improvement (e.g., with respect to clinical remission) may be relative to an appropriate reference treatment, e.g., a treatment without an anti-TL1A antibody.

[0112] "Recovery" means, for example, a reduction or improvement in one or more signs or symptoms of IBD (e.g., UC or CD) compared to no administration of the anti-TL1A antibody described herein. "Recovery" also includes a reduction or shortening of the duration of symptoms.

[0113] The terms “prevention” or “to prevent” refer to (a) preventing the occurrence of a disability, or (b) delaying the onset of a disability or the onset of its symptoms.

[0114] A treatment is considered "effectively improved" or "effectively reduced" when the assessment of IBD signs or symptoms is quantified by clinical measures relative to baseline, and during and / or after the treatment period. The difference between baseline and clinical measurements during / after treatment is compared and used to determine whether signs or symptoms have improved and whether the treatment is effective. This comparison may include comparison with placebo or one or more prior treatments.

[0115] As used interchangeably herein, “patient,” “individual,” or “subject” refers to a mammal. In one embodiment, the individual or subject is a human. In one embodiment, the individual requires treatment with a pharmaceutical or antibody disclosed herein.

[0116] The terms "pharmaceutical composition" or "pharmaceutical preparation" refer to a preparation of an antibody and one or more pharmaceutically acceptable carriers or excipients.

[0117] "Pharmacologically acceptable carriers" refer to components in a pharmaceutical composition or formulation other than the active ingredient, which are non-toxic to the subject and are not limited to buffers, excipients, stabilizers, surfactants, and / or preservatives.

[0118] The term "subcutaneous administration" refers to the administration of a substance into the subcutaneous layer.

[0119] II. Treatment of inflammatory bowel disease using anti-TL1A antibodies In some embodiments, the Disclosure provides a method for treating a patient with inflammatory bowel disease (IBD) (e.g., ulcerative colitis (UC) or Crohn's disease (CD)), the method comprising administering to the patient an effective amount of anti-TNF-like ligand 1A (TL1A) antibody (e.g., the anti-TL1A antibody provided herein in Section III) in a dosing regimen comprising at least a first phase (e.g., an induction phase), the first phase (e.g., an induction phase) comprising only four doses of anti-TL1A antibody, wherein (i) the second dose of anti-TL1A antibody is administered about two weeks after the first dose; (ii) the third dose of anti-TL1A antibody is administered about four weeks after the second dose; and (iii) the fourth dose of anti-TL1A antibody is administered about four weeks after the third dose.

[0120] In some embodiments, the Disclosure provides a method for treating a patient's IBD (e.g., UC or CD), the method comprising administering an effective amount of anti-TL1A antibody (e.g., anti-TL1A antibody provided herein in Section III) to the patient in a dosing regimen comprising a first phase (e.g., induction phase) and a second phase (e.g., maintenance phase), wherein (a) the first phase (e.g., induction phase) comprises only four doses of anti-TL1A antibody, (i) the second dose of anti-TL1A antibody is administered about two weeks after the first dose; (ii) the third dose of anti-TL1A antibody is administered about four weeks after the second dose; and (iii) the fourth dose of anti-TL1A antibody is administered about four weeks after the third dose; and (b) the second phase (e.g., maintenance phase) comprises administration of anti-TL1A antibody every four weeks. In some embodiments, the anti-TL1A antibody comprises the following complementarity-determining regions (CDRs): (a) CDR-H1 containing the amino acid sequence of SEQ ID NO: 3; (b) CDR-H2 containing the amino acid sequence of SEQ ID NO: 4; (c) CDR-H3 containing the amino acid sequence of SEQ ID NO: 5; (d) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6; (e) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7; and (f) CDR-L3 containing the amino acid sequence of SEQ ID NO: 8. In some embodiments, the anti-TL1A antibody is afimkibart.

[0121] This disclosure also provides anti-TL1A antibodies for use in treating IBD in patients according to the methods provided herein, and the use of anti-TL1A antibodies in the manufacture of pharmaceuticals for treating IBD according to the methods provided herein.

[0122] As a general principle, the treatment of IBD with anti-TL1A antibodies is described in PCT publication number WO 2021 / 260577 and U.S. Patent Application Publication number US 2023 / 0235070 A1, which are incorporated herein by reference for all purposes.

[0123] The treatment methods and related uses provided herein may include one, two, or all three of the following: Phase 1 (e.g., induction phase), Phase 2 (e.g., maintenance phase), and Extension phase.

[0124] A. 1st period Any method for treating IBD provided herein may include administration of an anti-TL1A antibody in at least one phase (e.g., the induction phase). The induction phase may include one or more administrations of the anti-TL1A antibody (e.g., one, two, three, or four administrations of the anti-TL1A antibody).

[0125] In some embodiments, the first phase (e.g., the induction phase) comprises four administrations of anti-TL1A antibody, where (i) the second administration of anti-TL1A antibody is given approximately two weeks after the first administration; (ii) the third administration of anti-TL1A antibody is given approximately four weeks after the second administration; and (iii) the fourth administration of anti-TL1A antibody is given approximately four weeks after the third administration. In some embodiments, the first phase (e.g., the induction phase) has a duration of approximately 12 weeks, and (a) the first dose of anti-TL1A antibody is administered around day 1 of week 0 (e.g., day 1 ± 3 days); (b) the second dose of anti-TL1A antibody is administered around day 1 of week 2 (e.g., day 1 ± 3 days); (c) the third dose of anti-TL1A antibody is administered around day 1 of week 6 (e.g., day 1 ± 3 days); and (d) the fourth dose of anti-TL1A antibody is administered around day 1 of week 10 (e.g., day 1 ± 3 days). In some embodiments, the first phase (e.g., the induction phase) has a duration of approximately 12 weeks, and (a) the first dose of anti-TL1A antibody is administered on day 1 of week 0; (b) the second dose of anti-TL1A antibody is administered on day 1 of week 2; (c) the third dose of anti-TL1A antibody is administered on day 1 of week 6; and / or (d) the fourth dose of anti-TL1A antibody is administered on day 1 of week 10 (e.g., the first phase (e.g., the induction phase) is administered by one, two, three, or all four of (a), (b), (c), and (d)). In some embodiments, the first phase (e.g., the induction phase) has a duration of approximately 12 weeks, and (a) the first dose of anti-TL1A antibody is administered on day 1 of week 0; (b) the second dose of anti-TL1A antibody is administered on day 1 of week 2; (c) the third dose of anti-TL1A antibody is administered on day 1 of week 6; and (d) the fourth dose of anti-TL1A antibody is administered on day 1 of week 10.

[0126] Anti-TL1A antibodies may be administered in doses of, for example, 1, 5, 10, 25, 50, 100, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, or 1000 mg during the first phase (e.g., the induction phase). In some embodiments, each dose of anti-TL1A antibody during the first phase (e.g., the induction phase) is approximately 50 mg to approximately 600 mg, for example, approximately 50 mg to approximately 150 mg, approximately 150 mg to approximately 450 mg, approximately 150 mg to approximately 500 mg, or approximately 450 mg to approximately 600 mg. In some embodiments, the doses of anti-TL1A antibody in the first phase (e.g., the induction phase) are approximately 50 mg, 150 mg, 450 mg, 500 mg, or 600 mg. In some embodiments, the anti-TL1A antibody is administered in doses of 50, 150, or 450 mg during the first phase (e.g., the induction phase). In one embodiment, the anti-TL1A antibody is administered in a dose of approximately 500 mg (e.g., a dose of 500 mg) during the first phase (e.g., the induction phase). The dose in the first phase (e.g., the induction phase) can be administered by any means. Preferably, the dose in the first phase (e.g., the induction phase) is administered intravenously or subcutaneously. In some embodiments, during the first phase (e.g., the induction phase), the anti-TL1A antibody is administered intravenously (IV) at a dose of approximately 500 mg (e.g., a 500 mg dose) (for example, each dose in the first phase (e.g., the induction phase) includes an IV administration of approximately 500 mg (e.g., 500 mg) of anti-TL1A antibody).

[0127] In some embodiments, during the first phase (e.g., the induction phase), the anti-TL1A antibody is administered subcutaneously (SC) in a dose of approximately 500 mg (e.g., a 500 mg dose) (for example, each dose in the first phase (e.g., the induction phase) includes an SC administration of approximately 500 mg (e.g., 500 mg) of anti-TL1A antibody).

[0128] Accordingly, in some embodiments, the present disclosure provides a method for treating a patient's IBD (e.g., UC or CD), the method comprising administering an effective amount of anti-TL1A antibody (e.g., anti-TL1A antibody provided herein in Section III) to the patient in a dosing regimen comprising a first phase (e.g., induction phase), comprising only four intravenous administrations of anti-TL1A antibody in doses of about 500 mg, the first phase (e.g., induction phase) having a duration of about 12 weeks, where (a) the first dose of anti-TL1A antibody is administered on day 1 of week 0; (b) the second dose of anti-TL1A antibody is administered on day 1 of week 2; (c) the third dose of anti-TL1A antibody is administered on day 1 of week 6; and (d) the fourth dose of anti-TL1A antibody is administered on day 1 of week 10. In some embodiments, the anti-TL1A antibody comprises the following CDRs: (a) CDR-H1 containing the amino acid sequence of SEQ ID NO: 3; (b) CDR-H2 containing the amino acid sequence of SEQ ID NO: 4; (c) CDR-H3 containing the amino acid sequence of SEQ ID NO: 5; (d) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6; (e) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7; and (f) CDR-L3 containing the amino acid sequence of SEQ ID NO: 8. In some embodiments, the anti-TL1A antibody is afimkibart.

[0129] In some embodiments, the Disclosure provides a method for treating a patient's IBD (e.g., UC or CD), the method comprising administering an effective amount of anti-TL1A antibody (e.g., the anti-TL1A antibody provided herein in Section III) to the patient in a dosing regimen comprising only four intravenous (IV) doses of anti-TL1A antibody in doses of about 500 mg, the four doses of anti-TL1A antibody being administered over about 12 weeks, (a) the first IV dose of anti-TL1A antibody being administered on day 1 of week 0; (b) the second IV dose of anti-TL1A antibody being administered on day 1 of week 2; (c) the third IV dose of anti-TL1A antibody being administered on day 1 of week 6; and (d) the fourth IV dose of anti-TL1A antibody being administered on day 1 of week 10. In some embodiments, the anti-TL1A antibody comprises the following CDRs: (a) CDR-H1 containing the amino acid sequence of SEQ ID NO: 3; (b) CDR-H2 containing the amino acid sequence of SEQ ID NO: 4; (c) CDR-H3 containing the amino acid sequence of SEQ ID NO: 5; (d) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6; (e) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7; and (f) CDR-L3 containing the amino acid sequence of SEQ ID NO: 8. In some embodiments, the anti-TL1A antibody is afimkibart.

[0130] In some embodiments, the Disclosure provides a method for treating a patient's IBD (e.g., UC or CD), the method comprising administering an effective amount of anti-TL1A antibody to the patient in a dosing regimen comprising a first phase (e.g., induction phase), the first phase (e.g., induction phase) comprising only four doses of anti-TL1A antibody, wherein (i) the second dose of anti-TL1A antibody is administered approximately two weeks after the first dose; (ii) the third dose of anti-TL1A antibody is administered approximately four weeks after the second dose; and (iii) the fourth dose of anti-TL1A antibody is administered approximately four weeks after the third dose; the anti-TL1A antibody comprises (a) a heavy chain variable (VH) domain having at least 95% sequence identity with the amino acid sequence of SEQ ID NO: 1; and / or (b) a light chain variable (VL) domain having at least 95% sequence identity with the amino acid sequence of SEQ ID NO: 2.

[0131] In some embodiments, the present disclosure provides a method for treating a patient's IBD (e.g., UC or CD), the method comprising administering an effective amount of anti-TL1A antibody to the patient in a drug regimen including a first phase (e.g., induction phase), the first phase (e.g., induction phase) comprising only four doses of anti-TL1A antibody, (i) the second dose of anti-TL1A antibody is administered approximately two weeks after the first dose; (ii) the third dose of anti-TL1A antibody is administered approximately four weeks after the second dose; and (iii) the fourth dose of anti-TL1A antibody is administered approximately four weeks after the third dose; the anti-TL1A antibody is (I) the amino acid sequence of Sequence ID No. 1 (II) A heavy chain variable (VH) domain containing an amino acid sequence having at least 95% sequence identity with (II) the amino acid sequence of SEQ ID NO: 2 and / or a light chain variable (VL) domain containing an amino acid sequence having at least 95% sequence identity with (II) the amino acid sequence of SEQ ID NO: 2, and including the following CDRs: (a) CDR-H1 containing the amino acid sequence of SEQ ID NO: 3; (b) CDR-H2 containing the amino acid sequence of SEQ ID NO: 4; (c) CDR-H3 containing the amino acid sequence of SEQ ID NO: 5; (d) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6; (e) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7; and (f) CDR-L3 containing the amino acid sequence of SEQ ID NO: 8.

[0132] In some embodiments, the Disclosure provides a method for treating a patient's IBD (e.g., UC or CD), the method comprising administering an effective amount of anti-TL1A antibody to the patient in a dosing regimen comprising only four intravenous doses of anti-TL1A antibody, the second intravenous dose of anti-TL1A antibody being administered approximately two weeks after the first dose; (ii) the third intravenous dose of anti-TL1A antibody being administered approximately four weeks after the second dose; and (iii) the fourth intravenous dose of anti-TL1A antibody being administered approximately four weeks after the third dose; the anti-TL1A antibody comprising (a) a VH domain comprising an amino acid sequence having at least 95% sequence identity with the amino acid sequence of SEQ ID NO: 1; and / or (b) a VL domain comprising an amino acid sequence having at least 95% sequence identity with the amino acid sequence of SEQ ID NO: 2.

[0133] In some embodiments, the present disclosure provides a method for treating a patient's IBD (e.g., UC or CD), the method comprising administering an effective amount of anti-TL1A antibody to the patient in a dosing regimen comprising only four IV doses of anti-TL1A antibody, the second IV dose of anti-TL1A antibody being administered approximately two weeks after the first dose; (ii) the third IV dose of anti-TL1A antibody being administered approximately four weeks after the second dose; and (iii) the fourth IV dose of anti-TL1A antibody being administered approximately four weeks after the third dose; the anti-TL1A antibody comprising (I) the amino acid sequence of SEQ ID NO: 1 and at least 95% The CDR comprises a heavy chain variable (VH) domain containing an amino acid sequence having sequence identity and / or a light chain variable (VL) domain containing an amino acid sequence having at least 95% sequence identity with the amino acid sequence of SEQ ID NO: 2, and includes the following CDRs: (a) CDR-H1 containing the amino acid sequence of SEQ ID NO: 3; (b) CDR-H2 containing the amino acid sequence of SEQ ID NO: 4; (c) CDR-H3 containing the amino acid sequence of SEQ ID NO: 5; (d) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6; (e) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7; and (f) CDR-L3 containing the amino acid sequence of SEQ ID NO: 8.

[0134] In some embodiments, the Disclosure provides a method for treating a patient's IBD (e.g., UC or CD), the method comprising administering an effective amount of anti-TL1A antibody to the patient in a dosing regimen comprising a first phase (e.g., induction phase), the first phase (e.g., induction phase) comprising only four doses of anti-TL1A antibody, wherein (i) the second dose of anti-TL1A antibody is administered approximately two weeks after the first dose; (ii) the third dose of anti-TL1A antibody is administered approximately four weeks after the second dose; and (iii) the fourth dose of anti-TL1A antibody is administered approximately four weeks after the third dose; the anti-TL1A antibody comprises (a) a VH domain containing the amino acid sequence of SEQ ID NO: 1; and / or (b) a VL domain containing the amino acid sequence of SEQ ID NO: 2.

[0135] In some embodiments, the Disclosure provides a method for treating a patient's IBD (e.g., UC or CD), the method comprising administering an effective amount of anti-TL1A antibody to the patient in a dosing regimen comprising only four intravenous doses of anti-TL1A antibody, the second intravenous dose of anti-TL1A antibody being administered approximately two weeks after the first dose; (ii) the third intravenous dose of anti-TL1A antibody being administered approximately four weeks after the second dose; and (iii) the fourth intravenous dose of anti-TL1A antibody being administered approximately four weeks after the third dose; the anti-TL1A antibody comprising (a) a VH domain comprising the amino acid sequence of SEQ ID NO: 1; and / or (b) a VL domain comprising the amino acid sequence of SEQ ID NO: 2.

[0136] In some embodiments, the Disclosure provides a method for treating a patient's IBD (e.g., UC or CD), the method comprising administering an effective amount of anti-TL1A antibody to the patient in a dosing regimen comprising a first phase (e.g., induction phase), the first phase (e.g., induction phase) comprising only four doses of anti-TL1A antibody, (i) the second dose of anti-TL1A antibody is administered approximately two weeks after the first dose; (ii) the third dose of anti-TL1A antibody is administered approximately four weeks after the second dose; and (iii) the fourth dose of anti-TL1A antibody is administered approximately four weeks after the third dose; the anti-TL1A antibody comprises (a) a heavy chain containing an amino acid sequence having at least 95% sequence identity with SEQ ID NO: 9; and / or (b) a light chain containing an amino acid sequence having at least 95% sequence identity with SEQ ID NO: 10. In some embodiments, the anti-TL1A antibody is afimkibart.

[0137] In some embodiments, the present disclosure provides a method for treating a patient's IBD (e.g., UC or CD), the method comprising administering an effective amount of anti-TL1A antibody to the patient in a drug regimen comprising a first phase (e.g., induction phase), the first phase (e.g., induction phase) comprising only four doses of anti-TL1A antibody, (i) the second dose of anti-TL1A antibody is administered approximately two weeks after the first dose; (ii) the third dose of anti-TL1A antibody is administered approximately four weeks after the second dose; and (iii) the fourth dose of anti-TL1A antibody is administered approximately four weeks after the third dose; the anti-TL1A antibody is (I) The anti-TL1A antibody comprises a heavy chain containing an amino acid sequence having at least 95% sequence identity with SEQ ID NO: 9; and / or a light chain containing an amino acid sequence having at least 95% sequence identity with SEQ ID NO: 10, wherein the anti-TL1A antibody comprises the following CDRs: (a) CDR-H1 containing the amino acid sequence of SEQ ID NO: 3; (b) CDR-H2 containing the amino acid sequence of SEQ ID NO: 4; (c) CDR-H3 containing the amino acid sequence of SEQ ID NO: 5; (d) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6; (e) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7; and (f) CDR-L3 containing the amino acid sequence of SEQ ID NO: 8. In some embodiments, the anti-TL1A antibody is afimkibart.

[0138] In some embodiments, the Disclosure provides a method for treating a patient's IBD (e.g., UC or CD), the method comprising administering an effective amount of anti-TL1A antibody to the patient in a dosing regimen comprising only four IV doses of anti-TL1A antibody, the second IV dose of anti-TL1A antibody being administered approximately two weeks after the first dose; (ii) the third IV dose of anti-TL1A antibody being administered approximately four weeks after the second dose; and (iii) the fourth IV dose of anti-TL1A antibody being administered approximately four weeks after the third dose; the anti-TL1A antibody comprising (a) a heavy chain containing an amino acid sequence having at least 95% sequence identity with SEQ ID NO: 9; and / or (b) a light chain containing an amino acid sequence having at least 95% sequence identity with SEQ ID NO: 10. In some embodiments, the anti-TL1A antibody is afimkibart.

[0139] In some embodiments, the present disclosure provides a method for treating a patient's IBD (e.g., UC or CD), the method comprising administering an effective amount of anti-TL1A antibody to the patient in a dosing regimen comprising only four intravenous doses of anti-TL1A antibody, (i) the second intravenous dose of anti-TL1A antibody is administered approximately two weeks after the first dose; (ii) the third intravenous dose of anti-TL1A antibody is administered approximately four weeks after the second dose; and (iii) the fourth intravenous dose of anti-TL1A antibody is administered approximately four weeks after the third dose; the anti-TL1A antibody is (I) SEQ ID NO: 9 and less The anti-TL1A antibody comprises a heavy chain containing an amino acid sequence having 95% sequence identity; and / or (II) a light chain containing an amino acid sequence having at least 95% sequence identity with SEQ ID NO: 10, and includes the following CDRs: (a) CDR-H1 containing the amino acid sequence of SEQ ID NO: 3; (b) CDR-H2 containing the amino acid sequence of SEQ ID NO: 4; (c) CDR-H3 containing the amino acid sequence of SEQ ID NO: 5; (d) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6; (e) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7; and (f) CDR-L3 containing the amino acid sequence of SEQ ID NO: 8. In some embodiments, the anti-TL1A antibody is afimkibart. In some embodiments, the Disclosure provides a method for treating a patient's IBD (e.g., UC or CD), the method comprising administering an effective amount of anti-TL1A antibody to the patient in a dosing regimen comprising a first phase (e.g., induction phase), the first phase (e.g., induction phase) comprising only four doses of anti-TL1A antibody, wherein (i) the second dose of anti-TL1A antibody is administered approximately two weeks after the first dose; (ii) the third dose of anti-TL1A antibody is administered approximately four weeks after the second dose; and (iii) the fourth dose of anti-TL1A antibody is administered approximately four weeks after the third dose; the anti-TL1A antibody comprises (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 9; and (b) a light chain containing the amino acid sequence of SEQ ID NO: 10.

[0140] In some embodiments, the Disclosure provides a method for treating a patient's IBD (e.g., UC or CD), the method comprising administering an effective amount of anti-TL1A antibody to the patient in a dosing regimen comprising only four intravenous doses of anti-TL1A antibody, the second intravenous dose of anti-TL1A antibody being administered approximately two weeks after the first dose; (ii) the third intravenous dose of anti-TL1A antibody being administered approximately four weeks after the second dose; and (iii) the fourth intravenous dose of anti-TL1A antibody being administered approximately four weeks after the third dose; the anti-TL1A antibody comprising (a) a heavy chain comprising the amino acid sequence of SEQ ID NO: 9; and (b) a light chain comprising the amino acid sequence of SEQ ID NO: 10.

[0141] B. 2nd period Any method provided herein may include administration of an anti-TL1A antibody in a second phase (e.g., maintenance phase) following administration of an anti-TL1A antibody in a first phase (e.g., induction phase). The second phase (e.g., maintenance phase) may include one or more administrations of the anti-TL1A antibody.

[0142] Phase 2 (e.g., maintenance phase) can be initiated at any appropriate point after Phase 1 (e.g., induction phase). In some embodiments, the first dose of Phase 2 (e.g., maintenance phase) is administered approximately two weeks (e.g., two weeks) after the last dose of Phase 1 (e.g., induction phase). For example, in an embodiment where Phase 1 (e.g., induction phase) includes four doses of anti-TL1A antibody, the first dose of Phase 2 (e.g., maintenance phase) may be administered approximately two weeks (e.g., two weeks) after the fourth dose of Phase 1 (e.g., induction phase).

[0143] In some embodiments, the second phase (e.g., maintenance phase) includes at least two doses of anti-TL1A antibody, the time intervals between each individual dose (e.g., maintenance dose) in the second phase may be the same. In other embodiments, the time intervals between individual doses (e.g., maintenance doses) in the second phase are not the same. Individual doses in the second phase (e.g., maintenance phase) may be given at least daily, with at least one day between doses, at least one week between doses, at least two weeks between doses, at least three weeks between doses, at least one month between doses, at least two months between doses, at least three months between doses, at least four months between doses, at least five months between doses, or at least six months between doses. In one preferred embodiment, individual doses (e.g., maintenance dose) in the second phase are given with one month between doses.

[0144] In some embodiments, the second phase (e.g., maintenance phase) includes administration of anti-TL1A antibodies every four weeks (Q4W) (e.g., subcutaneously).

[0145] In some embodiments, the second phase (e.g., maintenance phase) includes administration of anti-TL1A antibodies every two weeks (Q2W) (e.g., subcutaneously).

[0146] In some embodiments, the second phase (e.g., maintenance phase) includes (i) at least one interval in which anti-TL1A antibody is administered every four weeks (Q4W) and (ii) at least one interval in which anti-TL1A antibody is administered every two weeks (Q2W). In some embodiments, the frequency of medication in the second phase (e.g., maintenance phase) of the subject is increased from Q4W to Q2W based on observation of disease exacerbation.

[0147] Anti-TL1A antibodies may be administered during the second phase (e.g., maintenance phase) in doses of, for example, 1, 5, 10, 25, 50, 100, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, or 1000 mg. In some embodiments, anti-TL1A antibodies are administered during the second phase (e.g., maintenance phase) in doses of 50, 150, or 450 mg. In one embodiment, anti-TL1A antibodies are administered during the second phase (e.g., maintenance phase) in a dose of approximately 150 mg (e.g., a dose of 150 mg). In another embodiment, anti-TL1A antibodies are administered during the second phase (e.g., maintenance phase) in a dose of approximately 450 mg (e.g., a dose of 450 mg). The second phase (e.g., maintenance phase) can be administered by any means (e.g., intravenously or subcutaneously). For example, in some embodiments, during the second phase (e.g., maintenance phase), the anti-TL1A antibody is administered subcutaneously in doses of 50, 150, or 450 mg. In some embodiments, the anti-TL1A antibody is administered subcutaneously every four weeks (Q4W) in doses of 50, 150, or 450 mg.

[0148] In some embodiments, during the second phase (e.g., maintenance phase), the anti-TL1A antibody is administered subcutaneously at a dose of approximately 150 mg (e.g., 150 mg) every four weeks. In some embodiments, during the second phase (e.g., maintenance phase), the anti-TL1A antibody is administered subcutaneously at a dose of approximately 150 mg (e.g., 150 mg) every two weeks. In some embodiments, each dose during the second phase (e.g., maintenance phase) is approximately 150 mg (e.g., 150 mg), and the second phase (e.g., maintenance phase) includes (i) at least one interval during which the anti-TL1A antibody is administered subcutaneously every four weeks (Q4W) and (ii) at least one interval during which the anti-TL1A antibody is administered subcutaneously every two weeks (Q2W).

[0149] In some embodiments, during the second phase (e.g., maintenance phase), the anti-TL1A antibody is administered subcutaneously at a dose of approximately 450 mg (e.g., 450 mg) every four weeks. In some embodiments, during the second phase (e.g., maintenance phase), the anti-TL1A antibody is administered subcutaneously at a dose of approximately 450 mg (e.g., 450 mg) every two weeks. In some embodiments, each dose during the second phase (e.g., maintenance phase) is approximately 450 mg (e.g., 450 mg), and the second phase (e.g., maintenance phase) includes (i) at least one interval during which the anti-TL1A antibody is administered subcutaneously every four weeks (Q4W) and (ii) at least one interval during which the anti-TL1A antibody is administered subcutaneously every two weeks (Q2W).

[0150] In some embodiments, the second phase (e.g., maintenance phase) includes at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or more than 25 administrations of anti-TL1A antibody.

[0151] In some embodiments, the second phase (e.g., maintenance phase) includes 11 doses of anti-TL1A antibody (e.g., 11 doses of anti-TL1A antibody administered in a Q4W dosing regimen). In some embodiments, the second phase (maintenance phase) has a duration of approximately 40 weeks.

[0152] Accordingly, in some embodiments, the present disclosure provides a method for treating a patient's IBD (e.g., UC or CD), the method comprising administering to the patient an effective amount of anti-TL1A antibody (e.g., anti-TL1A antibody provided herein in Section III) in a dosing regimen comprising a first phase and a second phase (e.g., induction phase and maintenance phase), (a) the first phase (e.g., induction phase) comprising four intravenous administrations of anti-TL1A antibody in doses of about 500 mg, (i) the second administration of anti-TL1A antibody being given about two weeks after the first administration; (ii) the third administration of anti-TL1A antibody being given about four weeks after the second administration; and (iii) the fourth administration of anti-TL1A antibody being given about four weeks after the third administration; and (b) the second phase (e.g., maintenance phase) comprising subcutaneous administration of anti-TL1A antibody in doses of about 150 mg every four weeks.

[0153] In some embodiments, the Disclosure provides a method for treating a patient's IBD (e.g., UC or CD), the method comprising administering an effective amount of anti-TL1A antibody (e.g., anti-TL1A antibody provided herein in Section III) to the patient in a dosing regimen comprising a first phase and a second phase (e.g., induction phase and maintenance phase), wherein (a) the first phase (e.g., induction phase) comprises four intravenous administrations of anti-TL1A antibody in doses of about 500 mg, (i) the second administration of anti-TL1A antibody is given about two weeks after the first administration; (ii) the third administration of anti-TL1A antibody is given about four weeks after the second administration; and (iii) the fourth administration of anti-TL1A antibody is given about four weeks after the third administration; and (b) the second phase (e.g., maintenance phase) comprises subcutaneous administration of anti-TL1A antibody in doses of about 450 mg every four weeks. In some embodiments, the anti-TL1A antibody comprises the following CDRs: (a) CDR-H1 containing the amino acid sequence of SEQ ID NO: 3; (b) CDR-H2 containing the amino acid sequence of SEQ ID NO: 4; (c) CDR-H3 containing the amino acid sequence of SEQ ID NO: 5; (d) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6; (e) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7; and (f) CDR-L3 containing the amino acid sequence of SEQ ID NO: 8. In some embodiments, the anti-TL1A antibody is afimkibart.

[0154] In some embodiments, the present disclosure provides a method for treating a patient's IBD (e.g., UC or CD) the method comprises administering an effective amount of anti-TL1A antibody (e.g., the anti-TL1A antibody provided in Section III of the present invention) to the patient in a dosing regimen comprising: (a) four intravenous doses of anti-TL1A antibody in doses of about 500 mg each, (i) the second IV dose of anti-TL1A antibody being administered about two weeks after the first IV dose; (ii) the third IV dose of anti-TL1A antibody being administered about four weeks after the second IV dose; and (iii) the fourth IV dose of anti-TL1A antibody being administered about four weeks after the third dose; and (b) subcutaneous doses of anti-TL1A antibody in doses of about 450 mg every four weeks. In some embodiments, the anti-TL1A antibody comprises the following CDRs: (a) CDR-H1 containing the amino acid sequence of SEQ ID NO: 3; (b) CDR-H2 containing the amino acid sequence of SEQ ID NO: 4; (c) CDR-H3 containing the amino acid sequence of SEQ ID NO: 5; (d) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6; (e) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7; and (f) CDR-L3 containing the amino acid sequence of SEQ ID NO: 8. In some embodiments, the anti-TL1A antibody is afimkibart.

[0155] In some embodiments, the present disclosure provides a method for treating a patient's IBD (e.g., UC or CD), the method comprising administering an effective amount of anti-TL1A antibody to the patient in a dosing regimen comprising a first phase and a second phase (e.g., induction phase and maintenance phase), where (a) the first phase (e.g., induction phase) comprises only four doses of anti-TL1A antibody, (i) the second dose of anti-TL1A antibody is administered approximately two weeks after the first dose; and (ii) the third dose of anti-TL1A antibody is administered approximately four weeks after the second dose. (iii) The fourth dose of anti-TL1A antibody is administered approximately four weeks after the third dose; and (b) the second phase (e.g., maintenance phase) comprises administration of anti-TL1A antibody every four weeks; the anti-TL1A antibody comprises (a) a heavy chain variable (VH) domain containing an amino acid sequence having at least 95% sequence identity with the amino acid sequence of SEQ ID NO: 1; and / or (b) a light chain variable (VL) domain containing an amino acid sequence having at least 95% sequence identity with the amino acid sequence of SEQ ID NO: 2.

[0156] In some embodiments, the present disclosure provides a method for treating a patient's IBD (e.g., UC or CD), the method comprising administering an effective amount of anti-TL1A antibody to the patient in a dosing regimen comprising a first phase and a second phase (e.g., induction phase and maintenance phase), (a) the first phase (e.g., induction phase) comprising only four doses of anti-TL1A antibody, (i) the second dose of anti-TL1A antibody being administered about two weeks after the first dose; (ii) the third dose of anti-TL1A antibody being administered about four weeks after the second dose; and (iii) the fourth dose of anti-TL1A antibody being administered about four weeks after the third dose; and (b) the second phase (e.g., maintenance phase) comprising four-week doses of anti-TL1A antibody The anti-TL1A antibody comprises (I) a heavy chain variable (VH) domain containing an amino acid sequence having at least 95% sequence identity with the amino acid sequence of SEQ ID NO: 1; and / or (II) a light chain variable (VL) domain containing an amino acid sequence having at least 95% sequence identity with the amino acid sequence of SEQ ID NO: 2, and includes the following CDRs: (a) CDR-H1 containing the amino acid sequence of SEQ ID NO: 3; (b) CDR-H2 containing the amino acid sequence of SEQ ID NO: 4; (c) CDR-H3 containing the amino acid sequence of SEQ ID NO: 5; (d) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6; (e) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7; and (f) CDR-L3 containing the amino acid sequence of SEQ ID NO: 8.

[0157] In some embodiments, the Disclosure provides a method for treating a patient's IBD (e.g., UC or CD), the method comprising administering an effective amount of anti-TL1A antibody to the patient in a dosing regimen comprising a first phase and a second phase (e.g., induction and maintenance phase), wherein (a) the first phase (e.g., induction phase) comprises only four doses of anti-TL1A antibody, (i) the second dose of anti-TL1A antibody is administered approximately two weeks after the first dose; (ii) the third dose of anti-TL1A antibody is administered approximately four weeks after the second dose; and (iii) the fourth dose of anti-TL1A antibody is administered approximately four weeks after the third dose; and (b) the second phase (e.g., maintenance phase) comprises four-week doses of anti-TL1A antibody, the anti-TL1A antibody comprising (a) a VH domain comprising the amino acid sequence of SEQ ID NO: 1; and / or (b) a VL domain comprising the amino acid sequence of SEQ ID NO: 2.

[0158] In some embodiments, the present disclosure provides a method for treating a patient's IBD (e.g., UC or CD), the method comprising administering an effective amount of anti-TL1A antibody to the patient in a dosing regimen comprising a first phase and a second phase (e.g., induction phase and maintenance phase), where (a) the first phase (e.g., induction phase) comprises only four doses of anti-TL1A antibody, (i) the second dose of anti-TL1A antibody is administered approximately two weeks after the first dose; and (ii) the third dose of anti-TL1A antibody is administered approximately four weeks after the second dose. (iii) The fourth dose of anti-TL1A antibody is administered approximately four weeks after the third dose; (b) The second phase (e.g., maintenance phase) comprises administration of anti-TL1A antibody every four weeks; the anti-TL1A antibody comprises (a) a heavy chain having at least 95% sequence identity with SEQ ID NO: 9 or having an amino acid sequence of SEQ ID NO: 9; and (b) a light chain having at least 95% sequence identity with SEQ ID NO: 10 or having an amino acid sequence of SEQ ID NO: 10. In some embodiments, the anti-TL1A antibody is afimkibart.

[0159] In some embodiments, the Disclosure provides a method for treating a patient's IBD (e.g., UC or CD), the method comprising administering an effective amount of anti-TL1A antibody to the patient in a dosing regimen comprising a first phase and a second phase (e.g., induction phase and maintenance phase), (a) the first phase (e.g., induction phase) comprising only four doses of anti-TL1A antibody, (i) the second dose of anti-TL1A antibody being administered approximately two weeks after the first dose; (ii) the third dose of anti-TL1A antibody being administered approximately four weeks after the second dose; and (iii) the fourth dose of anti-TL1A antibody being administered approximately four weeks after the third dose; and (b) the second phase (e.g., maintenance phase) comprising four weeks Each dose comprises an administration of an anti-TL1A antibody; the anti-TL1A antibody comprises (I) a heavy chain containing an amino acid sequence having at least 95% sequence identity with SEQ ID NO: 9; and (II) a light chain containing an amino acid sequence having at least 95% sequence identity with SEQ ID NO: 10; and the anti-TL1A antibody comprises the following CDRs: (a) CDR-H1 containing the amino acid sequence of SEQ ID NO: 3; (b) CDR-H2 containing the amino acid sequence of SEQ ID NO: 4; (c) CDR-H3 containing the amino acid sequence of SEQ ID NO: 5; (d) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6; (e) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7; and (f) CDR-L3 containing the amino acid sequence of SEQ ID NO: 8. In some embodiments, the anti-TL1A antibody is afimkibart.

[0160] In some embodiments, the Disclosure provides a method for treating a patient's IBD (e.g., UC or CD), the method comprising administering an effective amount of anti-TL1A antibody to the patient in a dosing regimen comprising a first phase and a second phase (e.g., induction and maintenance phases), wherein (a) the first phase (e.g., induction phase) comprises only four doses of anti-TL1A antibody, (i) the second dose of anti-TL1A antibody is administered approximately two weeks after the first dose; (ii) the third dose of anti-TL1A antibody is administered approximately four weeks after the second dose; and (iii) the fourth dose of anti-TL1A antibody is administered approximately four weeks after the third dose; and (b) the second phase (e.g., maintenance phase) comprises administration of anti-TL1A antibody every four weeks; the anti-TL1A antibody comprises (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 9; and (b) a light chain containing the amino acid sequence of SEQ ID NO: 10. In some embodiments, the anti-TL1A antibody is afimkibart.

[0161] In some embodiments, (a) the first dose of the anti-TL1A antibody in Phase 1 (e.g., the first induction dose) is administered around day 1 of week 0; (b) the second dose of the anti-TL1A antibody in Phase 1 (e.g., the second induction dose) is administered around day 1 of week 2; (c) the third dose of the anti-TL1A antibody in Phase 1 (e.g., the third induction dose) is administered around day 1 of week 6; (d) the fourth dose of the anti-TL1A antibody in Phase 1 (e.g., the fourth induction dose) is administered around day 1 of week 10; (e) the first dose of Phase 2 (e.g., the first maintenance dose) is administered around day 1 of week 12; and (f) subsequent doses of Phase 2 (e.g., subsequent maintenance doses) are administered around day 1 of weeks 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52.

[0162] In some embodiments, the present disclosure provides a method for treating a patient's IBD (e.g., UC or CD), the method comprising administering an effective amount of anti-TL1A antibody to the patient in a dosing regimen comprising: (a) four intravenous administrations of anti-TL1A antibody, the second IV administration of anti-TL1A antibody being given approximately two weeks after the first IV administration; (ii) the third IV administration of anti-TL1A antibody being given approximately four weeks after the second IV administration; and (iii) the fourth IV administration of anti-TL1A antibody being given approximately four weeks after the third IV administration; and (b) a dosing regimen comprising subcutaneous (SC) administration of anti-TL1A antibody every four weeks; the anti-TL1A antibody comprising (a) a VH domain having at least 95% sequence identity with the amino acid sequence of SEQ ID NO: 1; and / or (b) a VL domain having at least 95% sequence identity with the amino acid sequence of SEQ ID NO: 2.

[0163] In some aspects, the present disclosure provides a method for treating a patient's IBD (e.g., UC or CD), the method comprising administering an effective amount of anti-TL1A antibody to the patient in a dosing regimen comprising: (a) four intravenous administrations of anti-TL1A antibody, the second IV administration of anti-TL1A antibody being given approximately two weeks after the first IV administration; (ii) the third IV administration of anti-TL1A antibody being given approximately four weeks after the second IV administration; and (iii) the fourth IV administration of anti-TL1A antibody being given approximately four weeks after the third IV administration; and (b) administration in a dosing regimen comprising subcutaneous (SC) administration of anti-TL1A antibody every four weeks; Antibody A comprises (I) a heavy chain variable (VH) domain containing an amino acid sequence having at least 95% sequence identity with the amino acid sequence of SEQ ID NO: 1; and / or (II) a light chain variable (VL) domain containing an amino acid sequence having at least 95% sequence identity with the amino acid sequence of SEQ ID NO: 2, and includes the following CDRs: (a) CDR-H1 containing the amino acid sequence of SEQ ID NO: 3; (b) CDR-H2 containing the amino acid sequence of SEQ ID NO: 4; (c) CDR-H3 containing the amino acid sequence of SEQ ID NO: 5; (d) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6; (e) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7; and (f) CDR-L3 containing the amino acid sequence of SEQ ID NO: 8.

[0164] In some embodiments, the Disclosure provides a method for treating a patient's IBD (e.g., UC or CD), the method comprising administering an effective amount of anti-TL1A antibody to the patient in a dosing regimen comprising: (a) four intravenous administrations of anti-TL1A antibody, the second IV administration of anti-TL1A antibody being given approximately two weeks after the first IV administration; (ii) the third IV administration of anti-TL1A antibody being given approximately four weeks after the second IV administration; and (iii) the fourth IV administration of anti-TL1A antibody being given approximately four weeks after the third IV administration; and (b) a dosing regimen comprising subcutaneous (SC) administration of anti-TL1A antibody every four weeks, wherein the anti-TL1A antibody comprises (a) a VH domain comprising the amino acid sequence of SEQ ID NO: 1; and / or (b) a VL domain comprising the amino acid sequence of SEQ ID NO: 2.

[0165] In some embodiments, the present disclosure provides a method for treating a patient's IBD (e.g., UC or CD), the method comprising administering an effective amount of anti-TL1A antibody to the patient in a dosing regimen comprising: (a) four intravenous administrations of anti-TL1A antibody, the second IV administration of anti-TL1A antibody being given approximately two weeks after the first IV administration; (ii) the third IV administration of anti-TL1A antibody being given approximately four weeks after the second IV administration; and (iii) the fourth IV administration of anti-TL1A antibody being given approximately four weeks after the third IV administration; and (b) a dosing regimen comprising subcutaneous (SC) administration of anti-TL1A antibody every four weeks; the anti-TL1A antibody comprising (a) a heavy chain having at least 95% sequence identity with SEQ ID NO: 9; and (b) a light chain having at least 95% sequence identity with SEQ ID NO: 10.

[0166] In some embodiments, the present disclosure provides a method for treating a patient's IBD (e.g., UC or CD) in which an effective amount of anti-TL1A antibody is administered to the patient in a dosing regimen comprising: (a) four intravenous doses of anti-TL1A antibody, wherein (i) the second IV dose of anti-TL1A antibody is administered approximately two weeks after the first IV dose; (ii) the third IV dose of anti-TL1A antibody is administered approximately four weeks after the second IV dose; and (iii) the fourth IV dose of anti-TL1A antibody is administered approximately four weeks after the third IV dose; and (b) a dosing regimen comprising subcutaneous (SC) administration of anti-TL1A antibody every four weeks. The anti-TL1A antibody comprises (I) a heavy chain containing an amino acid sequence having at least 95% sequence identity with SEQ ID NO: 9; and (II) a light chain containing an amino acid sequence having at least 95% sequence identity with SEQ ID NO: 10, and the anti-TL1A antibody comprises the following CDRs: (a) CDR-H1 containing the amino acid sequence of SEQ ID NO: 3; (b) CDR-H2 containing the amino acid sequence of SEQ ID NO: 4; (c) CDR-H3 containing the amino acid sequence of SEQ ID NO: 5; (d) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6; (e) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7; and (f) CDR-L3 containing the amino acid sequence of SEQ ID NO: 8. In some embodiments, the anti-TL1A antibody is afimkibart.

[0167] In some embodiments, the present disclosure provides a method for treating a patient's IBD (e.g., UC or CD), the method comprising administering an effective amount of anti-TL1A antibody to the patient in a dosing regimen comprising: (a) four intravenous administrations of anti-TL1A antibody, the second IV administration of anti-TL1A antibody being given approximately two weeks after the first IV administration; (ii) the third IV administration of anti-TL1A antibody being given approximately four weeks after the second IV administration; and (iii) the fourth IV administration of anti-TL1A antibody being given approximately four weeks after the third IV administration; and (b) a dosing regimen comprising subcutaneous (SC) administration of anti-TL1A antibody every four weeks; the anti-TL1A antibody comprising (a) a heavy chain comprising the amino acid sequence of SEQ ID NO: 9; and (b) a light chain comprising the amino acid sequence of SEQ ID NO: 10.

[0168] In some embodiments, the anti-TL1A antibody is afimkibart. In some embodiments, (a) the first IV dose of the anti-TL1A antibody is administered around day 1 of week 0; (b) the second IV dose of the anti-TL1A antibody is administered around day 1 of week 2; (c) the third IV dose of the anti-TL1A antibody is administered around day 1 of week 6; (d) the fourth IV dose of the anti-TL1A antibody is administered around day 1 of week 10; (e) the first SC dose of the anti-TL1A antibody is administered around day 1 of week 12; and (f) subsequent SC doses of the anti-TL1A antibody are administered around day 1 of weeks 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52. In some embodiments, the drug regimen, including phases 1 and 2 (e.g., induction and maintenance phases), has a duration of approximately 52 weeks (e.g., a duration of 52 weeks).

[0169] C. Extension phase Any method provided herein may include (i) administration of anti-TL1A antibody in a first phase (e.g., induction phase) or (ii) administration of anti-TL1A antibody in a second phase (e.g., induction phase and maintenance phase) followed by administration of anti-TL1A antibody in an extension phase. For example, the extension phase may include (i) a first phase (e.g., induction phase) consisting only of IV administration of anti-TL1A antibody, or (ii) a first phase (e.g., induction phase) consisting only of IV administration of anti-TL1A antibody and a second phase (e.g., maintenance phase) consisting of SC administration of anti-TL1A antibody. The extension phase may include one or more administrations of anti-TL1A antibody.

[0170] The extension phase may be initiated at any appropriate time after the first phase (e.g., induction phase) or the second phase (e.g., maintenance phase). In some embodiments, the first dose of the extension phase is administered approximately four weeks (e.g., four weeks) after the last dose of the second phase (e.g., maintenance phase).

[0171] In some embodiments, the extension period includes at least two doses of anti-TL1A antibody, and the time intervals between each individual extension dose may be the same. In other embodiments, the time intervals between doses in each extension period are not the same. Each extension dose may be administered at least daily, at least one day apart, at least one week apart, at least two weeks apart, at least three weeks apart, at least one month apart, at least two months apart, at least three months apart, at least four months apart, at least five months apart, or at least six months apart. In one preferred embodiment, each extension dose is administered at one-month intervals.

[0172] In some embodiments, the extension period includes administration of anti-TL1A antibody every four weeks (Q4W).

[0173] In some embodiments, the extension period includes administration of anti-TL1A antibody every two weeks (Q2W).

[0174] In some embodiments, the prolongation period includes (i) at least one interval in which anti-TL1A antibody is administered every four weeks (Q4W) and (ii) at least one interval in which anti-TL1A antibody is administered every two weeks (Q2W). In some embodiments, the dosage frequency of the prolongation period for the subject is increased from Q4W to Q2W based on observation of disease exacerbation.

[0175] Anti-TL1A antibodies may be administered during the extension period in doses of, for example, 1, 5, 10, 25, 50, 100, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, or 1000 mg. In some embodiments, anti-TL1A antibodies are administered during the extension period in doses of 50, 150, or 450 mg. In one embodiment, anti-TL1A antibodies are administered during the extension period in a dose of approximately 150 mg (e.g., a 150 mg dose). In another embodiment, anti-TL1A antibodies are administered during the extension period in a dose of approximately 450 mg (e.g., a 450 mg dose). The dose during the extension period can be administered by any means (e.g., intravenously or subcutaneously). For example, in some embodiments, during the extension phase, the anti-TL1A antibody is administered subcutaneously in doses of 50, 150, or 450 mg. In some embodiments, the anti-TL1A antibody is administered subcutaneously in doses of 50, 150, or 450 mg every four weeks (Q4W).

[0176] In some embodiments, during the extension period, the anti-TL1A antibody is administered subcutaneously at a dose of approximately 150 mg (e.g., 150 mg) every four weeks. In some embodiments, during the extension period, the anti-TL1A antibody is administered subcutaneously at a dose of approximately 150 mg (e.g., 150 mg) every two weeks. In some embodiments, each dose during the extension period is approximately 150 mg (e.g., 150 mg), and the extension period includes (i) at least one interval during which the anti-TL1A antibody is administered subcutaneously every four weeks (Q4W) and (ii) at least one interval during which the anti-TL1A antibody is administered subcutaneously every two weeks (Q2W).

[0177] In some embodiments, during the extension period, the anti-TL1A antibody is administered subcutaneously at a dose of approximately 450 mg (e.g., 450 mg) every four weeks. In some embodiments, during the extension period, the anti-TL1A antibody is administered subcutaneously at a dose of approximately 450 mg (e.g., 450 mg) every two weeks. In some embodiments, each dose during the extension period is approximately 450 mg (e.g., 450 mg), and the extension period includes (i) at least one interval during which the anti-TL1A antibody is administered subcutaneously every four weeks (Q4W) and (ii) at least one interval during which the anti-TL1A antibody is administered subcutaneously every two weeks (Q2W).

[0178] In some embodiments, the extension period includes at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or more than 25 administrations of anti-TL1A antibody.

[0179] In some embodiments, one or more medication cycles in the extension phase are administered to patients who have experienced disease exacerbation during the second phase (e.g., the maintenance phase). In some embodiments, one or more medication cycles in the extension phase are administered to patients who have experienced disease exacerbation during a medication regimen that includes subcutaneous administration of anti-TL1A antibodies.

[0180] In some embodiments, one or more medication cycles in the extension phase are administered to patients who have experienced disease exacerbation during the first phase (e.g., the induction phase). In some embodiments, one or more medication cycles in the extension phase are administered to patients who have experienced disease exacerbation during a medication regimen that includes intravenous administration of anti-TL1A antibodies.

[0181] D. Corticosteroid tapering In some embodiments, the patient has received a stable dose of corticosteroids prior to treatment (e.g., oral corticosteroids, e.g., oral prednisone or its equivalent, oral budesonide, or budesonide multimatrix (MMX)), and the patient is tapered off from corticosteroids during a second phase (e.g., maintenance phase) or extension phase (e.g., corticosteroid administration is discontinued during a second phase (e.g., maintenance phase) or extension phase). In some embodiments, the patient is tapered off from corticosteroids during a drug regimen that includes subcutaneous administration of an anti-TL1A antibody. For example, the dose of corticosteroids may be tapered off by 5 mg per week or 2.5 mg per week.

[0182] In some embodiments, the patient receives orally administered prednisone or its equivalent at a dose greater than 10 mg per day during the induction phase, and tapering includes (i) gradually reducing the dose by 5 mg per week until the patient receives a dose of 10 mg per day; and then (ii) gradually reducing the dose by 2.5 mg per week until a dose of 0 mg per week is reached (for example, tapering the dose by 2.5 mg per week over three weeks).

[0183] In some embodiments, the patient receives oral prednisone or its equivalent at a dose of 10 mg or less per day during the induction phase, and tapering involves gradually reducing the dose by 2.5 mg per week until a dose of 0 mg per week is reached (for example, including tapering the dose by 2.5 mg per week over a maximum of 3 weeks).

[0184] In some embodiments, the patient receives orally administered budesonide or budesonide MMX at a dose of 9 mg or less per day during the induction phase, and tapering includes (i) administering a corticosteroid at a dose of 9 mg every other day for two weeks; (ii) administering a corticosteroid at a dose of 9 mg every three days for two weeks; and (iii) discontinuing the administration of the corticosteroid.

[0185] In some embodiments, the patient receives budesonide orally at a dose of 6 mg or less per day during the induction phase, and tapering involves gradually reducing the dose to 3 mg / day over two weeks, followed by discontinuation of budesonide administration.

[0186] E. Response to treatment Clinical response Following a drug regimen of anti-TL1A antibodies (e.g., after the first phase (e.g., induction regimen) and / or the second phase (e.g., maintenance regimen)), patients may experience improvement in the signs and symptoms of IBD characterized by a clinical response.

[0187] In some embodiments, IBD is UC, and the clinical response is defined as a reduction of at least 2 points and 30% in the modified Mayo score (mMS) from baseline, as well as a reduction of ≥1 in the rectal bleeding subscore (RBS) or an RBS of 0 or 1.

[0188] In some embodiments, IBD is considered a form of Crohn's disease, and the clinical response is defined as a reduction of at least 100 points in the Crohn's disease activity index (CDAI) from baseline.

[0189] In some embodiments, in a population of patients treated according to any one of the methods provided herein, the treatment results in an increased proportion of patients achieving a clinical response at the end of the first phase (e.g., the induction phase) compared to a reference population. For example, in some embodiments, the first phase (e.g., the induction phase) has a duration of approximately 12 weeks, and the treatment results in an increased proportion of patients achieving a clinical response at the 12th week. For example, in some embodiments, at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 80%, 95%, or 99% of patients (e.g., 1-10%, 10-20%, 20-30%, 30-40%, 40-50%, 50-60%, 60-70%, 70-80%, 80-90%, or 90-100%) achieve a clinical response by week 12. In some embodiments, the proportion of patients in a population achieving a clinical response at 12 weeks is at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 80%, 95%, or 99% greater than the proportion of patients achieving a clinical response at 12 weeks in a reference population. In some embodiments, in a population of patients treated according to any one of the methods provided herein, including a second phase (e.g., maintenance phase), the treatment results in an increased proportion of patients achieving a clinical response at the end of the second phase (e.g., maintenance phase) compared to a reference population. In some embodiments, the medication regimen has a duration of approximately 52 weeks, and the treatment results in an increased proportion of patients achieving a clinical response at 52 weeks. For example, in some embodiments, at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 80%, 95%, or 99% of patients (e.g., 1-10%, 10-20%, 20-30%, 30-40%, 40-50%, 50-60%, 60-70%, 70-80%, 80-90%, or 90-100%) achieve a clinical response by week 52.In some aspects, the proportion of patients in the patient population achieving a clinical response at week 52 is at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 80%, 95%, or 99% greater than the proportion of patients in the reference population achieving a clinical response at week 52.

[0190] In any of the methods provided herein, the reference population may be any population that serves as a suitable control. For example, in some embodiments, the reference population is a population of subjects having IBD (e.g., UC (e.g., moderately or severely active UC) or CD (e.g., moderately or severely active CD)) who have never been treated with an anti-TL1A antibody (e.g., treated with placebo).

[0191] Endoscopic response Following anti-TL1A antibody therapy regimens (e.g., after the first phase (e.g., induction regimen) and / or the second phase (e.g., maintenance regimen)), patients may experience improvement in the signs and symptoms of IBD characterized by an endoscopic response.

[0192] In some embodiments, IBD is UC, and the endoscopic response is defined as a Mayo endoscopy subscore of 0 or 1.

[0193] In some embodiments, IBD is a CD, and the endoscopic response is defined as a reduction in the simplified Crohn's disease endoscopic score (SES-CD) by at least 50% compared to baseline SES-CD.

[0194] In some embodiments, in a population of patients treated according to any one of the methods provided herein, the treatment results in an increased proportion of patients achieving an endoscopic response at the end of the first phase (e.g., the induction phase) compared to a reference population. For example, in some embodiments, the first phase (e.g., the induction phase) has a duration of approximately 12 weeks, and the treatment results in an increased proportion of patients achieving an endoscopic response at the 12th week. For example, in some embodiments, at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 80%, 95%, or 99% of patients (e.g., 1-10%, 10-20%, 20-30%, 30-40%, 40-50%, 50-60%, 60-70%, 70-80%, 80-90%, or 90-100%) achieve an endoscopic response by week 12. In some embodiments, the proportion of patients in a population achieving an endoscopic response at 12 weeks is at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 80%, 95%, or 99% greater than the proportion of patients achieving an endoscopic response at 12 weeks in a reference population. In some embodiments, in a population of patients treated according to any one of the methods provided herein, including a second phase (e.g., maintenance phase), the treatment results in an increased proportion of patients achieving an endoscopic response at the end of the second phase (e.g., maintenance phase) compared to a reference population. For example, in some embodiments, the medication regimen has a duration of approximately 52 weeks, and the treatment results in an increased proportion of patients achieving an endoscopic response at 52 weeks. For example, in some embodiments, at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 80%, 95%, or 99% of patients (e.g., 1-10%, 10-20%, 20-30%, 30-40%, 40-50%, 50-60%, 60-70%, 70-80%, 80-90%, or 90-100%) achieve an endoscopic response at 52 weeks.In some aspects, the proportion of patients in the patient population achieving an endoscopic response at week 52 is at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 80%, 95%, or 99% greater than the proportion of patients achieving an endoscopic response at week 52 in the reference population.

[0195] In any of the methods provided herein, the reference population may be any population that serves as a suitable control. For example, in some embodiments, the reference population is a population of subjects having IBD (e.g., UC (e.g., moderately or severely active UC) or CD (e.g., moderately or severely active CD)) who have never been treated with an anti-TL1A antibody (e.g., treated with placebo).

[0196] Clinical remission Following a first medication regimen (e.g., induction regimen) and / or a second medication regimen (e.g., maintenance regimen), patients may experience improvement in the signs and symptoms of IBD, characterized by clinical remission.

[0197] In some embodiments, in a population of patients treated according to any one of the methods provided herein, the treatment results in an increased proportion of patients achieving clinical remission at the end of the first phase (e.g., the induction phase) compared to a reference population. For example, in some embodiments, the first phase (e.g., the induction phase) has a duration of approximately 12 weeks, and the treatment results in an increased proportion of patients achieving clinical remission at the 12th week. For example, in some embodiments, at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 80%, 95%, or 99% of patients (e.g., 1-10%, 10-20%, 20-30%, 30-40%, 40-50%, 50-60%, 60-70%, 70-80%, 80-90%, or 90-100%) achieve clinical remission by week 12. In some aspects, the proportion of patients in the patient population achieving clinical remission at week 12 is at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 80%, 95%, or 99% greater than the proportion of patients achieving clinical remission at week 12 in the reference population.

[0198] In some embodiments, in a population of patients treated according to any one of the methods provided herein, including a second phase (e.g., maintenance phase), the treatment results in an increased proportion of patients achieving clinical remission at the end of the second phase (e.g., maintenance phase) compared to a reference population. In some embodiments, the medication regimen has a duration of approximately 52 weeks, and the treatment results in an increased proportion of patients achieving clinical remission at week 52. For example, in some embodiments, at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 80%, 95%, or 99% of patients (e.g., 1-10%, 10-20%, 20-30%, 30-40%, 40-50%, 50-60%, 60-70%, 70-80%, 80-90%, or 90-100%) achieve clinical remission at week 52. In some aspects, the proportion of patients in the patient population achieving clinical remission at week 52 is at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 80%, 95%, or 99% greater than the proportion of patients achieving clinical remission at week 52 in the reference population.

[0199] In some embodiments, in a population of patients treated according to any one of the methods provided herein, including a maintenance phase, the treatment results in an increased proportion of patients experiencing maintenance of remission throughout the second phase (e.g., the maintenance phase) compared to a reference population. For example, in some embodiments, the first phase (e.g., the induction phase) has a duration of approximately 12 weeks, the entire medication regimen has a duration of approximately 52 weeks, and the treatment increases the proportion of patients experiencing clinical remission at weeks 12 and 52.

[0200] In some embodiments, IBD is UC, and clinical remission is defined as a modified Mayo score (mMS) ≤ 2, with a bowel movement frequency subscore (SFS) = 0 or 1, a rectal bleeding subscore (RBS) = 0, and an endoscopy subscore (ES) = 0 or 1. mMS is assessed as a composite based on three assessments, which are described in more detail below: bowel movement frequency subscore (SFS), rectal bleeding subscore (RFS), and endoscopy subscore (ES). Each of these assessments has a scoring range of 0 to 3, with higher values ​​indicating greater severity. mMS is calculated as the sum of SFS, RBS, and ES, ranging from 0 to 9.

[0201] SFS and RBS are calculated as the average over the seven days prior to the relevant point in time.

[0202] SFS is quantified as follows: Under the baseline, as defined, for each individual participant: 0 = Normal number of stool samples for this patient. 1 = 1-2 more flights than usual. 2 = 3-4 more flights than usual. 3 = 5 or more flights than usual.

[0203] RBS is quantified as follows: This represents the worst rectal bleeding observed by participants on that day: 0 = No blood is observed, or there is no bowel movement. 1 = Stool with blood lines. 2 = Stool with blood exceeding the line. 3 = Only blood passes through.

[0204] ES is quantified as follows: 0 = Normal appearance of the mucous membrane. 1 = Mild disease (erythema, decreased vascular pattern, no abrasion). 2 = Moderate disease (marked erythema, no vascular pattern, degree of abrasion, erosion). 3 = Severe illness (spontaneous bleeding, ulcer).

[0205] In other embodiments, the term “clinical remission” is based on a total Mayo score of 12 points: total Mayo score ≤ 2, with no individual subscores > 1. In some embodiments, the Per Adapted Mayo score is defined as an endoscopic subscore = 0 or 1, a decrease of 1 or more points from baseline to achieve a bowel movement frequency subscore = 0 or 1, and a rectal bleeding subscore = 0. In some embodiments, the Per Adapted Mayo score is defined as an endoscopic subscore = 0 or 1, a bowel movement frequency subscore = 0 or 1 (no increase from baseline), and a rectal bleeding subscore = 0.

[0206] In some embodiments, IBD is ulcerative colitis (UC), and clinical remission is defined as a Crohn's disease activity index (CDAI) of less than 150.

[0207] Endoscopic remission Following a first medication regimen (e.g., an induction regimen) and / or a second medication regimen (e.g., a maintenance regimen), patients may experience improvement in the signs and symptoms of IBD, characterized by endoscopic remission. The term “endoscopic remission” refers to a Mayo endoscopy subscore of 0. In some embodiments, patients experience endoscopic remission at or before the end of the first phase (e.g., the induction phase), for example, at 12 weeks of treatment or earlier. In some embodiments, in a population of patients treated according to any one of the methods provided herein, the treatment results in an increased proportion of patients achieving endoscopic remission at the end of the first phase (e.g., the induction phase) compared to a reference population. In some embodiments, patients experience endoscopic remission at or before the end of the second phase (e.g., the maintenance phase), for example, at 52 weeks of treatment or earlier. In some embodiments, in a population of patients treated according to any one of the methods provided herein, the treatment results in an increased proportion of patients who achieve endoscopic remission at the end of the second phase (e.g., the maintenance phase) compared to a reference population.

[0208] Deep remission Following a first medication regimen (e.g., induction regimen) and / or a second medication regimen (e.g., maintenance regimen), patients may experience improvement in the signs and symptoms of IBD, characterized by deep remission.

[0209] In some aspects, IBD is UC, and the term “deep remission” refers to a total Mayo score of 2 points or less, with no individual subscores exceeding 1 point, and both the endoscopic and rectal bleeding subscores being 0.

[0210] In some embodiments, in a population of patients treated according to any one of the methods provided herein, the treatment results in an increased proportion of patients achieving deep remission at the end of the first phase (e.g., the induction phase) compared to a reference population. In some embodiments, patients experience deep remission at or before the end of the second phase (e.g., the maintenance phase), for example, at 52 weeks of treatment or earlier. In some embodiments, in a population of patients treated according to any one of the methods provided herein, the treatment results in an increased proportion of patients achieving deep remission at the end of the second phase (e.g., the maintenance phase) compared to a reference population.

[0211] Symptomatic remission Following a first medication regimen (e.g., induction regimen) and / or a second medication regimen (e.g., maintenance regimen), patients may experience improvement in the signs and symptoms of IBD, characterized by symptomatic remission.

[0212] In some aspects, IBD is UC, and the term “symptomatic remission” refers to a total Mayo score of 2 points or less, with no individual subscores exceeding 1 point, and both the rectal bleeding and bowel movement frequency subscores being 0.

[0213] In some embodiments, in a population of patients treated according to any one of the methods provided herein, the treatment results in an increased proportion of patients achieving symptomatic remission at the end of the first phase (e.g., the induction phase) compared to a reference population. In some embodiments, patients experience symptomatic remission at or before the end of the second phase (e.g., the maintenance phase), for example, at or before week 52 of the treatment. In some embodiments, in a population of patients treated according to any one of the methods provided herein, the treatment results in an increased proportion of patients achieving symptomatic remission at the end of the second phase (e.g., the maintenance phase) compared to a reference population.

[0214] Endoscopic improvement Following a first medication regimen (e.g., induction regimen) and / or a second medication regimen (e.g., maintenance regimen), patients may experience improvement in the signs and symptoms of IBD, characterized by endoscopic improvement.

[0215] In some embodiments, IBD is UC, and the term “endoscopic improvement” (“El”) refers to a decrease of one point or more in the Mayo endoscopic subscore or an absolute endoscopic score of 1 or less. In some embodiments, endoscopic improvement is defined as an endoscopic subscore of 0 or 1.

[0216] In some embodiments, patients experience endoscopic improvement at or before the end of the first phase (e.g., the induction phase), for example, at or before the 12th week of the procedure. In some embodiments, in a population of patients treated according to any one of the methods provided herein, the procedure results in an increased proportion of patients achieving endoscopic improvement at the end of the first phase (e.g., the induction phase) compared to a reference population. For example, in some embodiments, the first phase (e.g., the induction phase) has a duration of approximately 12 weeks, and the procedure results in an increased proportion of patients achieving endoscopic improvement at the 12th week. In some aspects, at least 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 80%, 95%, or 99% of patients (e.g., 1–10%, 10–20%, 20–30%, 30–40%, 40–50%, 50–60%, 60–70%, 70–80%, 80–90%, or 90–100%) of the patient population achieve endoscopic improvement by week 12.

[0217] In some aspects, the proportion of patients in the patient population achieving endoscopic improvement at week 12 is at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 80%, 95%, or 99% greater than the proportion of patients achieving endoscopic improvement at week 12 in the reference population.

[0218] In some embodiments, patients experience endoscopic improvement at or before the end of the second phase (e.g., the maintenance phase), for example, at or before week 52 of the procedure. In some embodiments, in a population of patients treated according to any one of the methods provided herein, the procedure results in an increased proportion of patients achieving endoscopic improvement at the end of the second phase (e.g., the maintenance phase) compared to a reference population. In some aspects, at least 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 80%, 95%, or 99% of patients (e.g., 1–10%, 10–20%, 20–30%, 30–40%, 40–50%, 50–60%, 60–70%, 70–80%, 80–90%, or 90–100%) of the patient population achieve endoscopic improvement at week 52.

[0219] In some aspects, the proportion of patients in the patient population achieving endoscopic improvement at week 52 is at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 80%, 95%, or 99% greater than the proportion of patients achieving endoscopic improvement at week 52 in the reference population.

[0220] Improvement of IBD signs and symptoms Following a first medication regimen (e.g., induction regimen) and / or a second medication regimen (e.g., maintenance regimen), the patient may experience improvement in the signs and symptoms of IBD that are maintained while the patient is receiving the second medication regimen (e.g., maintenance regimen).

[0221] In some aspects of this disclosure, a first drug regimen (e.g., induction regimen) and / or a second drug regimen (e.g., maintenance regimen) using an anti-TL1A antibody effectively improves the signs and symptoms of IBD at least 12 weeks after initiation of treatment with the anti-TL1A antibody. These improvements in the signs and symptoms of IBD may be characterized by improvements in the Mayo endoscopic subscore. The reduction in the patient's Mayo endoscopic subscore may be at least 1, 2, or 3, or a greater integer.

[0222] Improvement in the signs and symptoms of IBD may be characterized in patients with a Mayo endoscopic subscore of 0 or 1, 2 or 3. Improvement in the signs and symptoms of IBD may be characterized in patients with a total Mayo subscore of 0, 1, 2 or 3. Improvement in the signs and symptoms of IBD may be characterized in patients with a Roberts histopathology index (RHI) of less than 5. Improvement in the signs and symptoms of IBD may be characterized in patients with a Geboes index of less than 3.2.

[0223] Improvement in the signs and symptoms of IBD may be maintained for at least 2, 3, 4, 6, or 12 months during a second medication regimen (e.g., a maintenance regimen).

[0224] F. Pretreatment In some cases, the patient has been previously treated for IBD (e.g., for UC) and has experienced an inadequate response to treatment, loss of response to treatment, and / or intolerance to treatment.

[0225] In some embodiments, the treatment was a conventional treatment for UC, including, for example, the administration of steroids, immunomodulators, or oral aminosalicylates (e.g., the patient has experienced an inadequate response, loss of response, and / or intolerance to steroids, immunomodulators, and / or oral aminosalicylates).

[0226] In some embodiments, the treatment was an advanced treatment for UC, and included, for example, the administration of antitumor necrosis factor (TNF) agents, antiintegrin agents, anti-IL12 / IL23 agents, Janus kinase (JAK) inhibitors, or sphingosine-1-phosphate (S1P) inhibitors (e.g., the patient had experienced an inadequate response, loss of response, and / or intolerance to anti-TNF agents, antiintegrin agents, anti-IL12 / IL23 agents, JAK inhibitors, or S1P inhibitors). Thus, in some embodiments, the patient had received prior advanced treatment at baseline (e.g., before the first dose during the induction phase). In other embodiments, the patient had not received prior advanced treatment at baseline.

[0227] In some embodiments, patients were receiving corticosteroid treatment at baseline (e.g., before the first dose during the induction phase). In other embodiments, patients were not receiving corticosteroid treatment at baseline.

[0228] G. Inflammatory bowel disease ulcerative colitis In some aspects, IBD is ulcerative colitis (UC).

[0229] In some embodiments, UC is moderate to severe active UC. In some embodiments, moderate to severe active UC is UC with a modified Mayo score (mMS) of 5 to 9 points. In some embodiments, moderate to severe active UC is UC with an mMS of 5 to 9 points and a Mayo endoscopic score (ES) of 2 or 3. Thus, in some embodiments, patients to be treated according to the methods provided herein have UC with an mMS of 5 to 6 or UC with an mMS of 7 to 9.

[0230] In some cases, patients with “moderate to severe” UC have 6 to 10 emergency bowel movements per day with occasional bleeding. In some cases, patients with “severe” UC have more than 10 emergency bloody stools per day. Patients with moderate to severe active UC may also have abdominal pain, fatigue, and weight loss. In some embodiments, the Disclosure features a method for treating a patient's UC (e.g., moderate to severe active UC), the method comprising administering an effective dose of anti-TL1A antibody to the patient in a dosing regimen comprising a first phase (e.g., induction phase) and a second phase (e.g., maintenance phase), wherein (a) the first phase (e.g., induction phase) comprises only four intravenous doses of anti-TL1A antibody at doses of approximately 500 mg each, (i) the second dose of anti-TL1A antibody is administered approximately two weeks after the first dose; (ii) the third dose of anti-TL1A antibody is administered approximately four weeks after the second dose; and (iii) the fourth dose of anti-TL1A antibody is administered approximately four weeks after the third dose; and (b) the second phase (e.g., maintenance phase) comprises subcutaneous administration of anti-TL1A antibody at doses of approximately 150 mg every four weeks. In some embodiments, the Disclosure features a method for treating a patient's UC (e.g., moderate to severe active UC), the method comprising administering an effective dose of anti-TL1A antibody to the patient in a dosing regimen comprising a first phase (e.g., induction phase) and a second phase (e.g., maintenance phase), wherein (a) the first phase (e.g., induction phase) comprises only four intravenous doses of anti-TL1A antibody at doses of approximately 500 mg each, (i) the second dose of anti-TL1A antibody is administered approximately two weeks after the first dose; (ii) the third dose of anti-TL1A antibody is administered approximately four weeks after the second dose; and (iii) the fourth dose of anti-TL1A antibody is administered approximately four weeks after the third dose; and (b) the second phase (e.g., maintenance phase) comprises subcutaneous administration of anti-TL1A antibody at doses of approximately 450 mg every four weeks. In some embodiments, the anti-TL1A antibody comprises the following CDRs: (a) CDR-H1 containing the amino acid sequence of SEQ ID NO: 3; (b) CDR-H2 containing the amino acid sequence of SEQ ID NO: 4; (c) CDR-H3 containing the amino acid sequence of SEQ ID NO: 5; (d) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6; (e) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7; and (f) CDR-L3 containing the amino acid sequence of SEQ ID NO: 8.In some embodiments, the anti-TL1A antibody is afimkibart.

[0231] Crohn's disease In some forms, IBD is Crohn's disease (CD).

[0232] In some embodiments, the CD is moderate to severely active CD. In some embodiments, a patient with moderate to severely active CD has (a) a simplified endoscopic score of 6 or higher for Crohn's disease (SES-CD), or (b) only isolated ileal disease and an SES-CD of 4 or higher. In some embodiments, a patient with moderate to severely active CD has (a) an SES-CD of 6 or higher, or (b) only isolated ileal disease and an SES-CD of 4 or higher, and a Crohn's disease activity index (CDAI) of at least 220 and ≤ 450. Thus, in some embodiments, a patient to be treated according to the method provided herein has CDAI score between 220 and ≤ 450 and an SES-CD of 6 or higher (or ≥ 4 for isolated ileal disease only).

[0233] In some embodiments, the Disclosure features a method for treating CD (e.g., moderate to severe active CD), the method comprising administering an effective dose of anti-TL1A antibody to a patient in a dosing regimen comprising a first phase (e.g., induction phase) and a second phase (e.g., maintenance phase), wherein (a) the first phase (e.g., induction phase) comprises only four intravenous doses of anti-TL1A antibody at doses of approximately 500 mg each, (i) the second dose of anti-TL1A antibody is administered approximately two weeks after the first dose; (ii) the third dose of anti-TL1A antibody is administered approximately four weeks after the second dose; and (iii) the fourth dose of anti-TL1A antibody is administered approximately four weeks after the third dose; and (b) the second phase (e.g., maintenance phase) comprises subcutaneous administration of anti-TL1A antibody at doses of approximately 150 mg every four weeks. In some embodiments, the Disclosure features a method for treating CD (e.g., moderate to severe active CD), the method comprising administering an effective dose of anti-TL1A antibody to a patient in a dosing regimen comprising a first phase (e.g., induction phase) and a second phase (e.g., maintenance phase), wherein (a) the first phase (e.g., induction phase) comprises only four intravenous doses of anti-TL1A antibody at doses of approximately 500 mg each, (i) the second dose of anti-TL1A antibody is administered approximately two weeks after the first dose; (ii) the third dose of anti-TL1A antibody is administered approximately four weeks after the second dose; and (iii) the fourth dose of anti-TL1A antibody is administered approximately four weeks after the third dose; and (b) the second phase (e.g., maintenance phase) comprises subcutaneous administration of anti-TL1A antibody at doses of approximately 450 mg every four weeks. In some embodiments, the anti-TL1A antibody comprises the following CDRs: (a) CDR-H1 containing the amino acid sequence of SEQ ID NO: 3; (b) CDR-H2 containing the amino acid sequence of SEQ ID NO: 4; (c) CDR-H3 containing the amino acid sequence of SEQ ID NO: 5; (d) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6; (e) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7; and (f) CDR-L3 containing the amino acid sequence of SEQ ID NO: 8. In some embodiments, the anti-TL1A antibody is afimkibart.

[0234] Patient H is a non-carrier of TNFSF15 haplotype B. In some embodiments, any method, use, or composition provided herein includes determining the patient's TNFSF15 haplotype (e.g., determining whether the patient is (a) a TNFSF15 haplotype B carrier or (b) a TNFSF15 haplotype B non-carrier). The method, use, or composition may further include making a treatment decision based on the patient's TNFSF15 haplotype. In some embodiments, a patient identified for treatment by the method provided herein is a TNFSF15 haplotype B non-carrier (e.g., determined to be a TNFSF15 haplotype B non-carrier).

[0235] Haplotype B is defined as the TNFSF15 gene region having nucleotides T / C / A / T / C at positions 15,524; 9,706; -358; -638; and 12,506, respectively, based on the reference sequence GenBank NM_005118.2, with the first nucleotide of the exon 1 start site designated as position 1 in the TNFSF15 gene region encoding the TL1A gene (haplotype positions 26 / 31 / 35 / 36 / 41, respectively (provided in Yamazaki et al., Human Molecular Genetics, 14(22):3499-3506, 2005)) (Table 1). A subject is identified as haplotype B if it is heterozygous or homozygous for haplotype B, i.e., if one or both copies of a gene region are haplotype B (i.e., if one or both copies of the TNFSF15 gene region have nucleotides T / C / A / T / C (26 / 31 / 35 / 36 / 41) at haplotype positions 15,524;9,706;-358;-638; and-12,506). [Table 1]

[0236] Haplotype locations 15,524;9,706;-358;-638; and -12,506 (26, 31, 35, 36, and 41) correspond to the sites of SNPs rs3810936, rs6478108, rs6478109, rs7848647, and rs7869487, respectively, identified in the NIH NCBI dbSNP database (see Table 1). Haplotype B contains a reference nucleotide at each of these locations: therefore, the haplotype B TNFSF15 gene region can be identified by the absence of each of the SNPs rs3810936, rs6478108, rs6478109, rs7848647, and rs7869487 (i.e., the presence of a reference allele at each of these sites).

[0237] A non-carrier of haplotype B is defined as an object that does not possess the haplotype B TNFSF15 gene region. For example, a non-carrier of haplotype B may be homozygous for a non-haplotype B allele, such as haplotype A (for example, it may have nucleotides C / T / G / C / T at haplotype positions 26 / 31 / 35 / 36 / 41). (See, for example, Michelsen et al., PLoS One, 4(3):e4719, 2009).

[0238] I. Combination Therapy The anti-TL1A antibody of the present invention can be administered alone or used in combination therapy. For example, combination therapy may include administering the anti-TL1A antibody according to any of the methods provided herein and administering at least one additional therapeutic agent (e.g., one, two, three, four, five, or six additional therapeutic agents). In one embodiment, combination therapy includes administering the antibody of the present invention and administering at least one additional therapeutic agent. Exemplary therapeutic agents that may be administered in combination with the anti-TL1A antibody are provided below. Further therapeutic agents that may be administered in combination with the anti-TL1A antibody are provided, for example, in WO 2015 / 073580, US 20220390463 A1, WO / 2021 / 260577 and US 20230235070 A1, which are incorporated herein by reference in their entirety.

[0239] Such combination therapy includes combined administration (where two or more therapeutic agents are included in the same or separate pharmaceutical composition) and separate administration, in which case the administration of the anti-TL1A antibody may be performed before, concurrently with, and / or after the administration of one or more additional therapeutic agents. In one embodiment, the administration of the anti-TL1A antibody and the administration of the additional therapeutic agent are performed within approximately 1, 2, 3, 4, 5, or 6 days, within approximately 1, 2, or 3 weeks, or within approximately 1 month. In one embodiment, both the antibody and the additional therapeutic agent are administered to the patient on day 1 of the treatment.

[0240] In some embodiments, the present disclosure provides a pharmaceutical composition comprising one of the anti-TL1A antibodies provided herein and at least one additional therapeutic agent, for example, as described below.

[0241] Combination therapy for patients with ulcerative colitis (UC) Aminosalicylate In some embodiments, IBD is ulcerative colitis (UC) (e.g., moderate to severe active UC), and anti-TL1A antibodies are administered in combination with aminosalicylic acids, such as 5-aminosalicylic acid (5-ASA).

[0242] As a general principle, aminosalicylic acids may be administered as first-line treatment for mild to moderate ulcerative colitis (UC). In some embodiments, anti-TL1A antibodies are administered to patients who have been previously treated with aminosalicylic acids (e.g., patients who have experienced an inadequate response, loss of response, and / or intolerance to aminosalicylic acids). In other embodiments, anti-TL1A antibodies are administered in combination with aminosalicylic acids, for example, to patients who have not been previously treated with aminosalicylic acids and / or have not experienced a loss of response and / or intolerance to aminosalicylic acids.

[0243] Examples of aminosalicylates that may be used in the present invention include mesalamine (also known as mesalazine or 5-ASA), e.g., APRISO®, ASACOL®, ASACOL®HD, CANASA®, DELZICOL®, FIV-ASA, LIALDA (商標) Examples include, but are not limited to, OCTASA®, PENTASA®, ROWASA®, sfROWASA®, or SALOFALK®; sulfasalazine, e.g., AZULFIDINE®; orsalazine (e.g., DIPENTUM®); and valsalidide (e.g., COLAZAL® or GIAZO®). In some embodiments, aminosalicylates are administered orally (i.e., oral aminosalicylates, e.g., oral 5-ASA or oral prednisone). In other embodiments, aminosalicylates are administered topically and / or rectally.

[0244] steroid In some embodiments, IBD is UC (e.g., moderate to severe active UC), and anti-TL1A antibodies are administered in combination with steroids (e.g., corticosteroids).

[0245] As a general principle, corticosteroids may be administered to treat moderate to severe flares of UC (e.g., for short-term use). In some embodiments, anti-TL1A antibodies are administered to patients who have previously been treated with corticosteroids (e.g., patients who have experienced an inadequate response, loss of response, and / or intolerance to corticosteroids). In some embodiments, anti-TL1A antibodies are administered to patients who are corticosteroid-dependent (e.g., patients who cannot tape corticosteroids to below a threshold dose without experiencing active disease), and / or patients who were corticosteroid-dependent before treatment with anti-TL1A antibodies. In some embodiments, anti-TL1A antibodies are administered in combination with corticosteroids, for example, in patients who have never been previously treated with corticosteroids and / or have not experienced loss of response and / or intolerance to corticosteroids.

[0246] Examples of corticosteroids that may be used in the present invention include, but are not limited to, prednisone (e.g., RAYOS® or DELTASONE®), prednisolone, methylprednisolone (e.g., MEDROL®), and budesonide (e.g., oral budesonide) (e.g., UCERIS® or ENTOCORT® EC). In some embodiments, the corticosteroid is administered orally (e.g., oral prednisone or oral budesonide). In some embodiments, the corticosteroid is administered intravenously or rectally.

[0247] Immunomodulatory drugs In some embodiments, IBD is UC (e.g., moderate to severe active UC), and anti-TL1A antibodies are administered in combination with immunomodulatory agents.

[0248] As a general principle, immunomodulatory agents may be administered to achieve long-term immunosuppression and / or to save steroids. In some embodiments, anti-TL1A antibodies are administered to patients who have previously been treated with immunomodulatory agents (e.g., patients who have experienced an inadequate response, loss of response, and / or intolerance to immunomodulatory agents). In other embodiments, anti-TL1A antibodies are administered in combination with immunomodulatory agents, for example, to patients who have not been previously treated with immunomodulatory agents and / or have not experienced a loss of response and / or intolerance to immunomodulatory agents.

[0249] Exemplary immunomodulatory agents that may be used in the present invention include, but are not limited to, azathioprine (AZA) (e.g., IMURAN®) (e.g., oral AZA), 6-mercaptopurine (6-MP) (e.g., PURINETHOL® or PURIXAN®) (e.g., oral 6-MP), methotrexate (MTX) (e.g., MTX administered intramuscularly or subcutaneously), B-cell depletors (e.g., natalizumab or rituximab), lymphocyte depletors (e.g., alemtuzumab), cyclosporine, tacrolimus, sirolimus, and mycophenolate mofetil.

[0250] biological treatment In some embodiments, IBD is UC (e.g., moderate to severe active UC), and anti-TL1A antibodies are administered in combination with biological therapy.

[0251] As a general principle, biological therapies target inflammatory pathways and may be administered for the treatment of moderate to severe ulcerative colitis (UC). In some embodiments, anti-TL1A antibodies are administered to patients who have previously been treated with biological therapies (e.g., patients who have experienced an inadequate response, loss of response, and / or intolerance to biological therapies). In other embodiments, anti-TL1A antibodies are administered in combination with biological therapies, for example, to patients who have not previously been treated with biological therapies and / or have not experienced a loss of response and / or intolerance to biological therapies.

[0252] Exemplary biological therapies that may be used in the present invention include, but are not limited to, tumor necrosis factor (TNF) inhibitors, e.g., infliximab (e.g., REMICADE®, INFLECTRA®, AVSOLA®, or RENFLEXIS®), adalimumab (e.g., HUMIRA®), and golimumab (e.g., SIMPONI®); integrin inhibitors, e.g., vedolizumab (e.g., ENTYVIO®); IL-12 and / or IL-23 inhibitors (e.g., IL-12 / IL-23 inhibitors), e.g., ustekinumab (e.g., STELARA®), mirikizumab (e.g., OMVOH®), brazicumab, guselkumab (e.g., TREMFYA®), and risankizumab (e.g., SKYRIZI®); and cell death receptor 3 (DR3) inhibitors, e.g., SL-325.

[0253] Antitumor necrosis factor agent In some embodiments, IBD is UC (e.g., moderate to severe active UC), and anti-TL1A antibodies are administered in combination with antitumor necrosis factor (TNF) agents (e.g., TNF inhibitors, blockers, or modulators).

[0254] In some embodiments, anti-TL1A antibodies are administered to patients who have previously been treated with anti-TNF agents (e.g., patients who have experienced an inadequate response, loss of response, and / or intolerance to anti-TNF agents). In other embodiments, anti-TL1A antibodies are administered in combination with anti-TNF agents, for example, to patients who have not been previously treated with anti-TNF agents and / or have not experienced a loss of response and / or intolerance to anti-TNF agents.

[0255] Exemplary anti-TNF agents that can be used in the present invention include, but are not limited to, infliximab (e.g., REMICADE®, INFLECTRA®, AVSOLA®, or RENFLEXIS®), adalimumab (e.g., HUMIRA®), golimumab (e.g., SIMPONI®), pegcetacoplan (e.g., XPRO™ or XPRO1595™), balixafortide (SAR441566), bendralizumab, R-7050, and apremilast (e.g., OTEZLA®). In some embodiments, the anti-TNF agent that can be used in the present invention is a small molecule inhibitor of TNF. Small molecule inhibitors of TNF include, but are not limited to, pegcetacoplan (e.g., XPRO™ or XPRO1595™), balixafortide (SAR441566), bendralizumab, R-7050, and apremilast (e.g., OTEZLA®).

[0256] Anti-integrin agent In some embodiments, IBD is UC (e.g., moderate to severe active UC), and the anti-TL1A antibody is administered in combination with an anti-integrin agent (e.g., an integrin inhibitor).

[0257] In some embodiments, the anti-TL1A antibody is administered to patients who have been previously treated with an anti-integrin agent (e.g., patients who have experienced an insufficient response to, loss of response to, and / or intolerance to an anti-integrin agent). In other embodiments, the anti-TL1A antibody is administered in combination with an anti-integrin agent in patients who, for example, have not been previously treated with an anti-integrin agent and / or have not experienced a loss of response to and / or intolerance to an anti-integrin agent.

[0258] Exemplary anti-integrin agents that can be used in the present invention include, but are not limited to, vedolizumab (e.g., ENTYVIO®).

[0259] Anti-IL-12 / IL-23 agent In some embodiments, the IBD is UC (e.g., moderate to severe active UC), and the anti-TL1A antibody is administered in combination with an anti-IL-12 / IL-23 agent (e.g., an IL-12 / IL-23 inhibitor).

[0260] In some embodiments, the anti-TL1A antibody is administered to patients previously treated with an anti-IL-12 / IL-23 agent (e.g., patients who have experienced an insufficient response to, loss of response to, and / or intolerance to an anti-IL-12 / IL-23 agent). In other embodiments, the anti-TL1A antibody is administered in combination with an anti-IL-12 / IL-23 agent in patients who, for example, have not been previously treated with an anti-IL-12 / IL-23 agent and / or have not experienced a loss of response to and / or intolerance to an anti-IL-12 / IL-23 agent.

[0261] Exemplary anti-IL-12 / IL-23 agents that can be used in the present invention include, but are not limited to, ustekinumab (e.g., STELARA®), mirikizumab (e.g., OMVOH®), brazikumab, guselkumab (e.g., TREMFYA®), risankizumab (e.g., SKYRIZI®), isphiline (LSF), and ikotrokinra (JNJ-2113). In some embodiments, the anti-IL-12 / IL-23 agent that can be used in the present invention is a small molecule inhibitor of IL-12 / IL-23. Examples of small molecule inhibitors of IL-12 / IL-23 include, but are not limited to, isphiline. In some embodiments, the anti-IL-12 / IL-23 agent is a synthetic peptide (e.g., ikotrokinra, e.g., oral ikotrokinra).

[0262] Cell death receptor 3 agent In some embodiments, the IBD is UC (e.g., moderate to severe active UC), and the anti-TL1A antibody is administered in combination with an anti-cell death receptor 3 (DR3) agent (e.g., a DR3 inhibitor). DR3 is also known as TNFRSF25.

[0263] In some embodiments, anti-TL1A antibodies are administered to patients who have previously been treated with anti-DR3 agents (e.g., patients who have experienced an inadequate response, loss of response, and / or intolerance to anti-DR3 agents). In other embodiments, anti-TL1A antibodies are administered in combination with anti-DR3 agents, for example, to patients who have not been previously treated with anti-DR3 agents and / or have not experienced a loss of response and / or intolerance to anti-DR3 agents.

[0264] Examples of anti-DR3 agents that may be used in the present invention include, but are not limited to, SL-325. In some embodiments, the anti-DR3 agent that may be used in the present invention is an anti-DR3 antibody (e.g., SL-325). In some embodiments, the anti-DR3 agent that may be used in the present invention is a small molecule inhibitor of DR3.

[0265] Janus kinase inhibitors In some embodiments, IBD is UC (e.g., moderate to severe active UC), and anti-TL1A antibodies are administered in combination with Janus kinase (JAK) inhibitors or JAK modulators.

[0266] As a general principle, JAK inhibitors may be administered orally to treat moderate to severe UC. In some embodiments, anti-TL1A antibodies are administered to patients who have been previously treated with JAK inhibitors (e.g., patients who have experienced an inadequate response, loss of response, and / or intolerance to JAK inhibitors). In other embodiments, anti-TL1A antibodies are administered in combination with JAK inhibitors, for example, to patients who have not been previously treated with JAK inhibitors and / or have not experienced a loss of response and / or intolerance to JAK inhibitors.

[0267] Exemplary JAK inhibitors that may be used in the present invention include, but are not limited to, tofacitinib (e.g., XELJANZ®), upadacitinib (e.g., RINVOQ®), pefitinib (e.g., SMYRAF®), and filgotinib (e.g., JYSELECA®).

[0268] Sphingosine-1-phosphate receptor modulators In some embodiments, IBD is UC (e.g., moderate to severe active UC), and anti-TL1A antibodies are administered in combination with sphingosine-1-phosphate (S1P) receptor modulators.

[0269] As a general principle, S1P receptor modulators may be administered as oral treatment for moderate UC. In some embodiments, anti-TL1A antibodies are administered to patients who have been previously treated with S1P receptor modulators (e.g., patients who have experienced an inadequate response, loss of response, and / or intolerance to S1P receptor modulators). In other embodiments, anti-TL1A antibodies are administered in combination with S1P receptor modulators, for example, to patients who have not been previously treated with S1P receptor modulators and / or have not experienced a loss of response and / or intolerance to S1P receptor modulators.

[0270] Examples of S1P receptor modulators that may be used in the present invention include, but are not limited to, ozanimod (e.g., ZEPOSIA®), etrasimodo (e.g., VELSIPITY®), and amicelimod.

[0271] miR-124 regulator In some embodiments, IBD is UC (e.g., moderate to severe active UC), and anti-TL1A antibodies are administered in combination with agents that modulate (e.g., upregulate) miR-124, such as obefazimod (ABX464).

[0272] antibiotics In some embodiments, IBD is UC (e.g., moderate to severe active UC), and anti-TL1A antibodies are administered in combination with antibiotics (e.g., antibiotics administered orally or intravenously).

[0273] As a general principle, antibiotics can be administered to treat complications of UC, such as pericystitis or secondary infections. Exemplary antibiotics that can be used in the present invention include, but are not limited to, ciprofloxacin, metronidazole, azithromycin and erythromycin.

[0274] Supportive and adjunctive treatments In some embodiments, the IBD is UC (e.g., moderate to severe active UC), and the anti-TL1A antibody is administered in combination with supportive or adjunctive treatments.

[0275] Exemplary supportive or adjunctive treatments that can be used in the present invention include, but are not limited to, probiotics (e.g., VSL#3® or VISBIOME®), prebiotics and / or dietary fiber (e.g., pectin, inulin, slippery elm, fructooligosaccharides or lactulose), iron supplements for the treatment of anemia, antihistamines and pain management agents (e.g., acetaminophen). In some embodiments, acetaminophen is preferred over NSAIDs for pain management.

[0276] Microbiome-based therapies In some embodiments, the IBD is UC (e.g., moderate to severe active UC), and the anti-TLIA antibody is administered in combination with microbiome-based therapies.

[0277] Exemplary microbiome-based therapies that can be used in the present invention include, but are not limited to, microbiome modulating therapies (e.g., SER-287) and fecal microbiota transplantation (FMT)-based treatments (e.g., RBX2660).

[0278] Stem cell therapy and gene therapy In some embodiments, the IBD is UC (e.g., moderate to severe active UC), and the anti-TLIA antibody is administered in combination with stem cell therapy or gene therapy.

[0279] Exemplary stem cell therapies or gene therapies that may be used in the present invention include, but are not limited to, therapies for UC-related tissue repair (e.g., mesenchymal stem cell (MSC) therapy), gene therapies targeting inflammation reduction, and therapies for autoimmune control (e.g., CAR-T cell therapy).

[0280] Herbal supplements and phytotherapy In some embodiments, IBD is UC (e.g., moderate to severe active UC), and anti-TL1A antibodies are administered in combination with herbal supplements and / or phytotherapy (e.g., plants, plant preparations (e.g., foods, teas, tinctures, poultices, creams, oils, ointments, balms, or lotions containing one or more plant-derived components), or extracts or other natural products from plants).

[0281] As a general principle, herbal supplements and phytotherapy having anti-inflammatory, antioxidant, antidiarrheal, antibacterial, digestive-improving, and / or softening properties may be administered to manage, alleviate, and / or improve symptoms associated with UC.

[0282] Exemplary plants, plant preparations, plant extracts, and products that may be used in the present invention include, but are not limited to, plants or plant preparations containing curcumin or the same (e.g., turmeric (Curcuma longa)), aloe vera (e.g., aloe vera juice or gel), chamomile (e.g., Matricaria chamomilla), wheatgrass, myrrh or plants or plant preparations containing the same (e.g., Commiphora myrha), berberine or plants or plant preparations containing the same (e.g., goldenseal or barberry), and elm (Ulmus rubra) or preparations thereof (e.g., bark or leaves); and / or traditional medicines (e.g., Chinese medicine). In some embodiments, herbal supplements or herbal remedies are administered orally (e.g., as oral vitamins, foods, teas, or tinctures). In other embodiments, herbal supplements or phytotherapy are administered topically (e.g., as poultices, creams, oils, ointments, balms, or lotions) and / or rectally (e.g., as herbal enemas).

[0283] Vagus nerve stimulation In some embodiments, IBD is ulcerative colitis (e.g., moderate to severe active UC), and anti-TL1A antibodies are administered in combination with vagus nerve stimulation (VNS) therapy, such as VNS devices or techniques.

[0284] Exemplary VNS therapies that may be used in the present invention include, but are not limited to, implantable or percutaneous nerve stimulation devices (e.g., VNS THERAPY® system or GAMMACORE® device). VNS therapies further include non-invasive vagus nerve stimulation techniques (e.g., diaphragmatic breathing, progressive muscle relaxation, and massage).

[0285] Combination therapy for Crohn's disease patients Aminosalicylate In some embodiments, the IBD is Crohn's disease (CD) (e.g., moderate to severe active CD), and the anti-TL1A antibody is administered in combination with an aminosalicylate, such as 5-aminosalicylic acid (5-ASA).

[0286] As a general principle, aminosalicylates can be administered for the treatment of mild to moderate CD. In some embodiments, the anti-TL1A antibody is administered to patients previously treated with aminosalicylates (e.g., patients who have experienced an inadequate response to, loss of response to, and / or intolerance to aminosalicylates). In other embodiments, the anti-TL1A antibody is administered in combination with an aminosalicylate in patients who, for example, have not been previously treated with aminosalicylates and / or have not experienced a loss of response to and / or intolerance to aminosalicylates.

[0287] Exemplary aminosalicylates that can be used in the present invention include mesalamine (also known as mesalazine or 5-ASA), such as APRISO®, ASACOL®, ASACOL® HD, CANASA®, DELZICOL®, FIV-ASA, LIALDA (商標) , OCTASA®, PENTASA®, ROWASA®, sfROWASA® or SALOFALK®; sulfasalazine, such as AZULFIDINE®; olsalazine (e.g., DIPENTUM®); and balsalazide (e.g., COLAZAL® or GIAZO®), but are not limited thereto. In some embodiments, the aminosalicylate is administered orally (i.e., an oral aminosalicylate, such as oral 5-ASA or oral prednisone). In other embodiments, the aminosalicylate is administered topically and / or rectally.

[0288] Steroid In some embodiments, IBD is CD (e.g., moderate to severe active CD), and anti-TL1A antibodies are administered in combination with steroids (e.g., corticosteroids).

[0289] As a general principle, corticosteroids may be administered to treat moderate to severe flares of CD (e.g., for short-term use). In some embodiments, anti-TL1A antibodies are administered to patients who have previously been treated with corticosteroids (e.g., patients who have experienced an inadequate response, loss of response, and / or intolerance to corticosteroids). In some embodiments, anti-TL1A antibodies are administered to patients who are corticosteroid-dependent (e.g., patients who cannot tape corticosteroids to below a threshold dose without experiencing active disease), and / or patients who were corticosteroid-dependent before treatment with anti-TL1A antibodies. In some embodiments, anti-TL1A antibodies are administered in combination with corticosteroids, for example, in patients who have never been previously treated with corticosteroids and / or have not experienced loss of response and / or intolerance to corticosteroids.

[0290] Examples of corticosteroids that may be used in the present invention include, but are not limited to, prednisone (e.g., RAYOS® or DELTASONE®), prednisolone, methylprednisolone (e.g., MEDROL®), and budesonide (e.g., oral budesonide) (e.g., UCERIS® or ENTOCORT® EC). In some embodiments, the corticosteroid is administered orally (e.g., oral prednisone or oral budesonide). In some embodiments, the corticosteroid is administered intravenously or rectally.

[0291] Immunomodulatory drugs In some embodiments, IBD is CD (e.g., moderate to severe active CD), and anti-TL1A antibodies are administered in combination with immunomodulatory agents.

[0292] As a general principle, immunomodulatory agents may be administered to achieve long-term immunosuppression and / or to save steroids. In some embodiments, anti-TL1A antibodies are administered to patients who have previously been treated with immunomodulatory agents (e.g., patients who have experienced an inadequate response, loss of response, and / or intolerance to immunomodulatory agents). In other embodiments, anti-TL1A antibodies are administered in combination with immunomodulatory agents, for example, to patients who have not been previously treated with immunomodulatory agents and / or have not experienced a loss of response and / or intolerance to immunomodulatory agents.

[0293] Exemplary immunomodulatory agents that may be used in the present invention include, but are not limited to, azathioprine (AZA) (e.g., IMURAN®) (e.g., oral AZA), 6-mercaptopurine (6-MP) (e.g., PURINETHOL® or PURIXAN®) (e.g., oral 6-MP), methotrexate (MTX) (e.g., MTX administered intramuscularly or subcutaneously), B-cell depletors (e.g., natalizumab or rituximab), lymphocyte depletors (e.g., alemtuzumab), cyclosporine, tacrolimus, sirolimus, and mycophenolate mofetil.

[0294] biological treatment In some embodiments, IBD is a form of CD (e.g., moderate to severe active CD), and anti-TL1A antibodies are administered in combination with biological therapy.

[0295] As a general principle, biological therapies target inflammatory pathways and may be administered for the treatment of moderate to severe C. leptomeria. In some embodiments, anti-TL1A antibodies are administered to patients who have previously been treated with biological therapies (e.g., patients who have experienced an inadequate response, loss of response, and / or intolerance to biological therapies). In other embodiments, anti-TL1A antibodies are administered in combination with biological therapies, for example, to patients who have not previously been treated with biological therapies and / or have not experienced a loss of response and / or intolerance to biological therapies.

[0296] Exemplary biological therapies that may be used in the present invention include tumor necrosis factor (TNF) inhibitors, e.g., infliximab (e.g., REMICADE®, INFLECTRA®, AVSOLA®, or RENFLEXIS®), adalimumab (e.g., HUMIRA®), and certolizumab pegol (e.g., CIMZIA®); and integrin inhibitors, e.g., vedolizumab (e.g., ENTYVIO®). )); IL-12 and / or IL-23 inhibitors (e.g., IL-12 / IL-23 inhibitors), e.g., ustekinumab (e.g., STELARA®), mirikizumab (e.g., OMVOH®), brazicumab, guselkumab (e.g., TREMFYA®), risankizumab (e.g., SKYRIZI®), and tildrakizumab; and cell death receptor 3 (DR3) inhibitors, e.g., SL-325, are included but not limited to these.

[0297] Antitumor necrosis factor agent In some embodiments, IBD is CD (e.g., moderate to severe active CD), and anti-TL1A antibodies are administered in combination with antitumor necrosis factor (TNF) agents (e.g., TNF inhibitors, blockers, or modulators).

[0298] In some embodiments, anti-TL1A antibodies are administered to patients who have previously been treated with anti-TNF agents (e.g., patients who have experienced an inadequate response, loss of response, and / or intolerance to anti-TNF agents). In other embodiments, anti-TL1A antibodies are administered in combination with anti-TNF agents, for example, to patients who have not been previously treated with anti-TNF agents and / or have not experienced a loss of response and / or intolerance to anti-TNF agents.

[0299] Examples of anti-TNF agents that may be used in the present invention include, but are not limited to, infliximab (e.g., REMICADE®, INFLECTRA®, AVSOLA®, or RENFLEXIS®), adalimumab (e.g., HUMIRA®), certolizumab pegol (e.g., CIMZIA®), pezipanemin (e.g., XPRO® or XPRO1595®), ballinatunfib (SAR441566), benpyrine, R-7050, and apremilast (e.g., OTEZLA®). In some embodiments, the anti-TNF agents that may be used in the present invention are small molecule inhibitors of TNF. Small molecule inhibitors of TNF include, but are not limited to, pezipanamine (e.g., XPRO® or XPRO1595®), ballinatanfib (SAR441566), benpyrine, R-7050, and apremilast (e.g., OTEZLA®).

[0300] Antiintegrin agents In some embodiments, IBD is UC (e.g., moderate to severe active UC), and anti-TL1A antibodies are administered in combination with anti-integrin agents (e.g., integrin inhibitors).

[0301] In some embodiments, anti-TL1A antibodies are administered to patients who have previously been treated with anti-integrin agents (e.g., patients who have experienced an inadequate response, loss of response, and / or intolerance to anti-integrin agents). In other embodiments, anti-TL1A antibodies are administered in combination with anti-integrin agents, for example, to patients who have not been previously treated with anti-integrin agents and / or have not experienced a loss of response and / or intolerance to anti-integrin agents.

[0302] Examples of antiintegrin agents that may be used in the present invention include, but are not limited to, vedolizumab (e.g., ENTYVIO®).

[0303] Anti-IL-12 / IL-23 agents In some embodiments, IBD is CD (e.g., moderate to severe active CD), and anti-TL1A antibodies are administered in combination with anti-IL-12 / IL-23 agents (e.g., IL-12 / IL-23 inhibitors).

[0304] In some embodiments, anti-TL1A antibodies are administered to patients who have previously been treated with anti-IL-12 / IL-23 agents (e.g., patients who have experienced an inadequate response, loss of response, and / or intolerance to anti-IL-12 / IL-23 agents). In other embodiments, anti-TL1A antibodies are administered in combination with anti-IL-12 / IL-23 agents in patients who have not been previously treated with anti-IL-12 / IL-23 agents and / or have not experienced a loss of response and / or intolerance to anti-IL-12 / IL-23 agents.

[0305] Examples of anti-IL-12 / IL-23 agents that may be used in the present invention include, but are not limited to, ustekinumab (e.g., STELARA®), mirikizumab (e.g., OMVOH®), brazicumab, guselkumab (e.g., TREMFYA®), risankizumab (e.g., SKYRIZI®), tildrakizumab, isophylline (LSF), and icotroquinra (JNJ-2113). In some embodiments, the anti-IL-12 / IL-23 agent that may be used in the present invention is a small molecule inhibitor of IL-12 / IL-23. Examples of small molecule inhibitors of IL-12 / IL-23 include, but are not limited to, isophylline. In some embodiments, the anti-IL-12 / IL-23 agent is a synthetic peptide (e.g., icotroquinra, e.g., orally administered icotroquinra).

[0306] Three drugs that target cell death receptors In some embodiments, IBD is CD (e.g., moderate to severe active CD), and anti-TL1A antibodies are administered in combination with anti-cell death receptor 3 (DR3) agents (e.g., DR3 inhibitors).

[0307] In some embodiments, anti-TL1A antibodies are administered to patients who have previously been treated with anti-DR3 agents (e.g., patients who have experienced an inadequate response, loss of response, and / or intolerance to anti-DR3 agents). In other embodiments, anti-TL1A antibodies are administered in combination with anti-DR3 agents, for example, to patients who have not been previously treated with anti-DR3 agents and / or have not experienced a loss of response and / or intolerance to anti-DR3 agents.

[0308] Examples of anti-DR3 agents that may be used in the present invention include, but are not limited to, SL-325. In some embodiments, the anti-DR3 agent that may be used in the present invention is an anti-DR3 antibody (e.g., SL-325). In some embodiments, the anti-DR3 agent that may be used in the present invention is a small molecule inhibitor of DR3.

[0309] Janus kinase inhibitors In some embodiments, IBD is CD (e.g., moderate to severe active CD), and anti-TL1A antibodies are administered in combination with Janus kinase (JAK) inhibitors or JAK modulators.

[0310] As a general principle, JAK inhibitors may be administered orally to treat moderate to severe C. difficile. In some embodiments, anti-TL1A antibodies are administered to patients who have previously been treated with JAK inhibitors (e.g., patients who have experienced an inadequate response, loss of response, and / or intolerance to JAK inhibitors). In other embodiments, anti-TL1A antibodies are administered in combination with JAK inhibitors, for example, to patients who have not been previously treated with JAK inhibitors and / or have not experienced a loss of response and / or intolerance to JAK inhibitors.

[0311] Exemplary JAK inhibitors that may be used in the present invention include, but are not limited to, tofacitinib (e.g., XELJANZ®), upadacitinib (e.g., RINVOQ®), pefitinib (e.g., SMYRAF®), and filgotinib (e.g., JYSELECA®).

[0312] Sphingosine-1-phosphate receptor modulators In some embodiments, IBD is CD (e.g., moderate to severe active CD), and anti-TL1A antibodies are administered in combination with sphingosine-1-phosphate (S1P) receptor modulators.

[0313] As a general principle, S1P receptor modulators may be administered as oral treatment for moderate CD. In some embodiments, anti-TL1A antibodies are administered to patients who have been previously treated with S1P receptor modulators (e.g., patients who have experienced an inadequate response, loss of response, and / or intolerance to S1P receptor modulators). In other embodiments, anti-TL1A antibodies are administered in combination with S1P receptor modulators, for example, to patients who have not been previously treated with S1P receptor modulators and / or have not experienced a loss of response and / or intolerance to S1P receptor modulators.

[0314] Examples of S1P receptor modulators that may be used in the present invention include, but are not limited to, ozanimod (e.g., ZEPOSIA®), etrasimodo (e.g., VELSIPITY®), and amicelimod.

[0315] miR-124 regulator In some embodiments, IBD is UC (e.g., moderate to severe active UC), and anti-TL1A antibodies are administered in combination with agents that modulate (e.g., upregulate) miR-124, such as obefazimod (ABX464).

[0316] antibiotics In some embodiments, IBD is CD (e.g., moderate to severe active CD), and anti-TL1A antibodies are administered in combination with antibiotics (e.g., antibiotics administered orally or intravenously).

[0317] As a general principle, antibiotics may be administered to treat complications of C. difficile, such as infections, abscesses, or fistulas. Exemplary antibiotics that may be used in this invention include, but are not limited to, ciprofloxacin, metronidazole, azithromycin, erythromycin, and rifaximin (e.g., rifamixin, used for overgrowth or complications of intestinal bacteria).

[0318] Support and auxiliary measures In some embodiments, IBD is CD (e.g., moderate to severe active CD), and anti-TL1A antibodies are administered in combination with supportive or adjunctive treatments.

[0319] Examples of supportive or adjunctive treatments that may be used in the present invention include, but are not limited to, probiotics (e.g., agents that modulate the gut microbiome, VSL#3® or VISBIOME®), prebiotics and / or dietary fiber (e.g., pectin, inulin, psyllium, fructooligosaccharides or lactulose), iron supplements for the treatment of anemia (e.g., anemia caused by chronic inflammation or blood loss), antihistamines and pain relievers (e.g., acetaminophen). In some embodiments, for example, acetaminophen is preferred over NSAIDs for pain management because NSAIDs may worsen CD symptoms.

[0320] Microbiome-based treatments In some embodiments, IBD is CD (e.g., moderate to severe active CD), and anti-TL1A antibodies are administered in combination with microbiome-based therapy.

[0321] Exemplary microbiome-based therapies that may be used in the present invention include, but are not limited to, microbiome-modulating therapies (e.g., SER-287) and fecal microbiota transplantation (FMT)-based treatments (e.g., RBX2660).

[0322] Stem cell therapy and gene therapy In some embodiments, IBD is CD (e.g., moderate to severe active CD), and anti-TL1A antibodies are administered in combination with stem cell therapy or gene therapy.

[0323] Exemplary stem cell therapies or gene therapies that may be used in the present invention include, but are not limited to, therapies for regeneration and inflammation control in CD (e.g., mesenchymal stem cell (MSC) therapy), gene therapies targeting inflammation reduction, and therapies for autoimmune control (e.g., CAR-T cell therapy).

[0324] Herbal supplements and phytotherapy In some embodiments, IBD is CD (e.g., moderate to severe active CD), and anti-TL1A antibodies are administered in combination with herbal supplements and / or phytotherapy (e.g., plants, plant preparations (e.g., foods, teas, tinctures, poultices, creams, oils, ointments, balms, or lotions containing one or more plant-derived components), or extracts or other natural products from plants).

[0325] As a general principle, herbal supplements and phytotherapy having anti-inflammatory, antioxidant, antidiarrheal, antibacterial, digestive-improving, and / or softening properties may be administered to manage, alleviate, and / or improve symptoms associated with C. difficile.

[0326] Exemplary plants, plant preparations, plant extracts, and products that may be used in the present invention include, but are not limited to, curcumin or plants or plant preparations containing it (e.g., turmeric (Curcuma longa)), boswellia (e.g., Boswellia serrata), chamomile (e.g., Matricaria chamomilla), myrrh or plants or plant preparations containing it (e.g., Commiphora myrha), berberine or plants or plant preparations containing it (e.g., goldenseal or barberry), and elm (Ulmus rubra) or preparations thereof (e.g., bark or leaves); and / or traditional medicines (e.g., Chinese medicine). In some embodiments, the herbal supplement or phytotherapy is administered orally (e.g., as an oral vitamin, food, tea, or tincture). In other embodiments, the herbal supplement or phytotherapy is administered topically (e.g., as a poultice, cream, oil, ointment, balm, or lotion) and / or rectally (e.g., as an herbal enema).

[0327] Vagus nerve stimulation In some embodiments, IBD is ulcerative colitis (e.g., moderate to severe active UC), and anti-TL1A antibodies are administered in combination with vagus nerve stimulation (VNS) therapy, such as VNS devices or techniques.

[0328] Exemplary VNS therapies that may be used in the present invention include, but are not limited to, implantable or percutaneous nerve stimulation devices (e.g., VNS THERAPY® system or GAMMACORE® device). VNS therapies further include non-invasive vagus nerve stimulation techniques (e.g., diaphragmatic breathing, progressive muscle relaxation, and massage).

[0329] III. Anti-TL1A antibody The method disclosed herein includes the administration of an anti-TL1A antibody. Exemplary anti-TL1A antibodies described herein are shown in Table 2. [Table 2] TIFF2026527426000003.tif142170

[0330] In some aspects of this disclosure, the anti-TL1A antibody comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 3, CDR-H2 containing the amino acid sequence of SEQ ID NO: 4, CDR-H3 containing the amino acid sequence of SEQ ID NO: 5, CDR-L1 containing the amino acid sequence of SEQ ID NO: 6, CDR-L2 containing the amino acid sequence of SEQ ID NO: 7, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 8. In some aspects, the anti-TL1A antibody comprises all 1, 2, 3, 4, 5, 6, 7, or 8 of the framework region sequences shown in SEQ ID NOs: 13-20.

[0331] In some aspects of this disclosure, the anti-TL1A antibody comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 12, CDR-H2 containing the amino acid sequence of SEQ ID NO: 4, CDR-H3 containing the amino acid sequence of SEQ ID NO: 5, CDR-L1 containing the amino acid sequence of SEQ ID NO: 6, CDR-L2 containing the amino acid sequence of SEQ ID NO: 7, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 8. In some aspects, the anti-TL1A antibody comprises 1, 2, 3, 4, 5, 6, 7, or all 8 of the framework region sequences shown in SEQ ID NOs: 14-21.

[0332] In some aspects of this disclosure, the anti-TL1A antibody comprises a heavy chain variable domain (VH) having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 1 (e.g., at least 96%, 97%, 98%, or 99% identity to SEQ ID NO: 1), and / or a light chain variable domain (VL) having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 2 (e.g., at least 96%, 97%, 98%, or 99% identity to SEQ ID NO: 2).

[0333] In some aspects of this disclosure, the anti-TL1A antibody comprises a VH domain containing the amino acid sequence of SEQ ID NO: 1 and / or a VL domain containing the amino acid sequence of SEQ ID NO: 2.

[0334] In some aspects of this disclosure, the anti-TL1A antibody comprises VH having the sequence shown in SEQ ID NO: 1 and VL having the sequence shown in SEQ ID NO: 2.

[0335] In some aspects of the present disclosure, the anti-TL1A antibody comprises (a) a heavy chain having at least 95% sequence identity with the amino acid sequence of SEQ ID NO: 9 or SEQ ID NO: 11 (e.g., having at least 96%, 97%, 98%, or 99% identity with SEQ ID NO: 9 or SEQ ID NO: 11); and / or (b) a light chain having at least 95% sequence identity with the amino acid sequence of SEQ ID NO: 10 (e.g., having at least 96%, 97%, 98%, or 99% identity with SEQ ID NO: 10).

[0336] In some embodiments, the anti-TL1A antibody comprises (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 9; and / or (b) a light chain containing the amino acid sequence of SEQ ID NO: 10.

[0337] In some embodiments of this disclosure, the anti-TL1A antibody comprises a heavy chain having the sequence shown in SEQ ID NO: 11. In some embodiments, the anti-TL1A antibody comprises a heavy chain having the sequence shown in SEQ ID NO: 11 and a light chain having the sequence shown in SEQ ID NO: 10, wherein the C-terminal lysine (K) of the heavy chain amino acid sequence of SEQ ID NO: 11 is optional. In some embodiments, the heavy chain does not have a C-terminal lysine (K). In some embodiments, the heavy chain has the sequence shown in SEQ ID NO: 9. In some embodiments, the anti-TL1A antibody comprises a heavy chain having the sequence shown in SEQ ID NO: 9 and a light chain having the sequence shown in SEQ ID NO: 10.

[0338] In some aspects of this disclosure, the anti-TL1A antibody is afimkibart (also known as RO7790121, RVT-3101, or PF-06480605).

[0339] Further exemplary anti-TL1A antibodies are shown in Table 3 and below. [Table 3] TIFF2026527426000005.tif248170TIFF2026527426000006.tif254170TIFF20265274260 00007.tif254170TIFF2026527426000008.tif254170TIFF2026527426000009.tif146170

[0340] In some aspects of this disclosure, the anti-TL1A antibody comprises VH encoded by the nucleic acid sequence of the insert of a vector deposited as 1 D1 1.31 VH having ATCC accession number PTA-120639, and VL encoded by the nucleic acid sequence of the insert of a vector deposited as 1 D1 1.31 VL having ATCC accession number PTA-120640.

[0341] In some aspects of this disclosure, an anti-TL1A antibody competes for binding with an anti-TL1A antibody comprising a variable heavy chain region having the sequence shown in SEQ ID NO: 1 and a variable light chain region having the sequence shown in SEQ ID NO: 2.

[0342] In some aspects of this disclosure, an anti-TL1A antibody competes for binding with an antibody comprising VH encoded by the nucleic acid sequence of an insert in a vector deposited as 1D1 1.31 VH having ATCC accession number PTA-120639, and VL encoded by the nucleic acid sequence of an insert in a vector deposited as 1D1 1.31 VL having ATCC accession number PTA-120640.

[0343] In some aspects of the present disclosure, the anti-TL1A antibody comprises a sequence pair selected from the group consisting of SEQ ID NOs: 2 and 22; SEQ ID NOs: 2 and 23; SEQ ID NOs: 2 and 24; SEQ ID NOs: 2 and 25; SEQ ID NOs: 2 and 26; SEQ ID NOs: 2 and 27; SEQ ID NOs: 2 and 28; SEQ ID NOs: 2 and 29; SEQ ID NOs: 2 and 30; SEQ ID NOs: 31 and 35; SEQ ID NOs: 32 and 36; SEQ ID NOs: 33 and 37; SEQ ID NOs: 34 and 38; SEQ ID NOs: 39 and 40; SEQ ID NOs: 41 and 42; SEQ ID NOs: 43 and 44; SEQ ID NOs: 45 and 54; SEQ ID NOs: 63 and 64; SEQ ID NOs: 71 and 72; SEQ ID NOs: 73 and 74; SEQ ID NOs: 75 and 74; SEQ ID NOs: 76 and 74; and SEQ ID NOs: 77 and 74.

[0344] In some aspects of this disclosure, the anti-TL1A antibody comprises CDR-H1 having the sequence shown in SEQ ID NO: 47, CDR-H2 having the sequence shown in SEQ ID NO: 49, CDR-H3 having the sequence shown in SEQ ID NO: 51, CDR-L1 having the sequence shown in SEQ ID NO: 56, CDR-L2 having the sequence shown in SEQ ID NO: 58, and CDR-L3 having the sequence shown in SEQ ID NO: 60.

[0345] In some aspects of this disclosure, the anti-TL1A antibody comprises a heavy chain framework region as shown in SEQ ID NOs: 46, 48, 50, and 52, and / or a light chain framework region as shown in SEQ ID NOs: 55, 57, 59, and 61.

[0346] In some aspects of this disclosure, the anti-TL1A antibody comprises a heavy chain variable region having the sequence shown in SEQ ID NO: 63 and a light chain variable region having the sequence shown in SEQ ID NO: 64.

[0347] In some aspects of this disclosure, the anti-TL1A antibody comprises a heavy chain tail sequence provided in SEQ ID NO: 53. In some aspects of this disclosure, the anti-TL1A antibody comprises a light chain tail sequence provided in SEQ ID NO: 62.

[0348] In some embodiments, the anti-TL1A antibody comprises the heavy chain variable region sequence of SEQ ID NO: 45 and / or the light chain variable region sequence of SEQ ID NO: 54.

[0349] In some aspects of this disclosure, the anti-TL1A antibody is thurisokivart.

[0350] In some embodiments, the antibody used in any of the methods, compositions, uses, and compositions for use provided herein is the anti-TL1A antibody provided in Table 2A of U.S. Patent No. 11,136,386, which is incorporated herein in whole by reference.

[0351] In some embodiments of any of the methods, compositions, uses, and compositions for use provided herein, the anti-TL1A antibody is the anti-TL1A antibody provided in U.S. Patent No. 10,322,174, U.S. Patent No. 10,689,439, U.S. Patent No. 11,292,848, U.S. Patent No. 10,138,296, U.S. Patent No. 10,822,422 and U.S. Patent No. 11,220,549, which are incorporated herein by reference in their entirety. In some embodiments, the anti-TL1A antibody comprises the CDR sequence of clone 320-179 provided in U.S. Patent No. 10,689,439. In some embodiments, the anti-TL1A antibody is clone 320-179 provided in U.S. Patent No. 10,689,439.

[0352] In some aspects of this disclosure, the anti-TL1A antibody comprises CDR-H1 having the sequence shown in SEQ ID NO: 65, CDR-H2 having the sequence shown in SEQ ID NO: 66, CDR-H3 having the sequence shown in SEQ ID NO: 67, CDR-L1 having the sequence shown in SEQ ID NO: 68, CDR-L2 having the sequence shown in SEQ ID NO: 69, and CDR-L3 having the sequence shown in SEQ ID NO: 70.

[0353] In some aspects of this disclosure, the anti-TL1A antibody comprises a heavy chain variable region having the sequence shown in SEQ ID NO: 71 and a light chain variable region having the sequence shown in SEQ ID NO: 72.

[0354] In some embodiments, the anti-TL1A antibody includes the heavy chain variable region sequence of SEQ ID NO: 73, 75, 76, or 77 and / or the light chain variable region sequence of SEQ ID NO: 74. In some embodiments, the anti-TL1A antibody includes the heavy chain variable region sequence of SEQ ID NO: 73, 75, 76, or 77 and the light chain variable region sequence of SEQ ID NO: 74. In some embodiments, the anti-TL1A antibody includes the heavy chain variable region sequence of SEQ ID NO: 73 and the light chain variable region sequence of SEQ ID NO: 74. In some embodiments, the anti-TL1A antibody includes the heavy chain variable region sequence of SEQ ID NO: 75 and the light chain variable region sequence of SEQ ID NO: 74. In some embodiments, the anti-TL1A antibody includes the heavy chain variable region sequence of SEQ ID NO: 76 and the light chain variable region sequence of SEQ ID NO: 74. In some embodiments, the anti-TL1A antibody includes the heavy chain variable region sequence of SEQ ID NO: 77 and the light chain variable region sequence of SEQ ID NO: 74.

[0355] In some aspects of this disclosure, the anti-TL1A antibody is TEV-48574.

[0356] In some aspects of this disclosure, the anti-TL1A antibody is C03V. C03V is described, for example, in Clarke AW, Poulton L, Shim D, Mabon D, Butt D, Pollard M, Pande V, Husten J, Lyons J, Tian C, Doyle AG. Anti-TL1A antibody for the treatment of asthma and inflammatory bowel disease. MAbs. 2018 May / Jun;10(4):664-677.doi:10.1080 / 19420862.2018.1440164.Epub 2018 Mar 5.PMID:29436901;PMCID:PMC5973687.

[0357] In some aspects of this disclosure, the anti-TL1A antibody is SPY002. SPY002 is described, for example, in Zhu, E., et al. "P911 Development and Characterization of SPY002, a Novel Extended Half-life Monoclonal Antibody Drug Candidate Targeting TL1A for the Treatment of IBD." Journal of Crohn's and Colitis 18. Supplement_1(2024):i1666-i1666.

[0358] In some aspects of this disclosure, the anti-TL1A antibody is FG-M701.

[0359] IV. Products and Kits In another aspect of the present invention, a product is provided containing a material useful for the treatment, prevention and / or diagnosis of the aforementioned disorders (e.g., inflammatory bowel disease (IBD), e.g., ulcerative colitis (UC), or Crohn's disease (CD)). The product comprises a container and a label or accompanying information attached to or accompanying the container. Suitable containers include, for example, bottles, vials, syringes, and IV solution bags. The container may be formed from a variety of materials, such as glass or plastic. The container may hold a composition (e.g., a composition comprising an anti-TL1A antibody) alone or in combination with another composition effective for treating, preventing and / or diagnosing a condition, and may have a sterile access port (e.g., the container may be an intravenous solution bag or a vial with a stopper that can be punctured by a subcutaneous needle). At least one active agent in the composition is the antibody of the present invention (e.g., an anti-TL1A antibody, e.g., afimkibart). The label or accompanying information indicates that the composition is used to treat a selected condition (e.g., IBD, e.g., UC, or CD). Furthermore, the product may comprise (a) a first container containing a composition comprising the antibody of the present invention; and (b) a second container containing a composition comprising a further therapeutic agent. The product in this embodiment of the present invention may further include a document indicating that the composition may be used to treat a particular condition (e.g., IBD, e.g., UC or CD). Alternatively, or in addition thereto, the product may further comprise a second (or third) container containing a pharmaceutically acceptable buffer, e.g., bacteriostatic water for injection (BWFI), phosphate-buffered saline, Ringer's solution, and dextrose solution. This may further comprise other materials desirable from a commercial and user perspective, including other buffers, diluents, filters, needles, and syringes.

[0360] This disclosure also provides kits comprising any or all of the anti-TL1A antibodies described herein. The kits of this disclosure comprise one or more containers comprising the anti-TL1A antibodies described herein, and instructions for use according to any of the methods of this disclosure described herein. Generally, these instructions include instructions for the administration of the anti-TL1A antibodies for the therapeutic treatment described herein. In some embodiments, kits are provided for preparing single-dose units. In certain embodiments, the kit may comprise both a first container containing a dry protein and a second container containing an aqueous formulation. In certain embodiments, kits may comprise single and multi-chamber prefilled syringes (e.g., liquid syringes and rio-syringes).

[0361] Instructions for the use of anti-TL1A antibodies generally include information regarding the dosage, dosage schedule, and route of administration for the intended treatment. Containers may be unit doses, bulk packages (e.g., multi-dose packages), or sub-unit doses. Instructions supplied within the kits of this disclosure are typically written instructions on labels or accompanying documents (e.g., on paper sheets included in the kit), but machine-readable instructions (e.g., instructions delivered on magnetic or optical storage disks) may also be acceptable.

[0362] The kits of this disclosure are in appropriate packaging. Appropriate packaging includes, but is not limited to, vials, bottles, jars, flexible packaging (e.g., sealed Mylar or plastic bags), etc. Packaging is also intended for use in combination with specific devices such as inhalers, nasal administration devices (e.g., nebulizers), or infusion devices such as minipumps. The kits may have a sterile access port (e.g., the container may be an intravenous solution bag or vial with a stopper that can be punctured by a subcutaneous needle). The container may have a sterile access port (e.g., the container may be an intravenous solution bag or vial with a stopper that can be punctured by a subcutaneous needle). At least one active agent in the composition is an anti-TL1A antibody. The container may further contain a second pharmaceutically active agent.

[0363] The kit may optionally provide additional components such as buffers and interpretation information. Typically, the kit includes a container and labels or accompanying documents on or attached to the container.

[0364] V. Compositions and Formulations A. Composition In further embodiments, pharmaceutical compositions comprising an effective amount of the anti-TL1A antibody described herein and such pharmaceutical compositions for use in any of the treatment methods provided herein are provided. In one embodiment, the pharmaceutical composition comprises one of the antibodies provided herein and a pharmaceutically acceptable carrier. In another embodiment, the pharmaceutical composition comprises one of the antibodies provided herein and at least one additional therapeutic agent, for example, one of those described below.

[0365] The anti-TL1A antibody pharmaceutical compositions (formulations) described herein can be prepared by combining the antibody with a pharmaceutically acceptable carrier or excipient known to those skilled in the art. See, for example, Remington's Pharmaceutical Sciences 16th edition, Osol, A. Ed. (1980) and Falconer RJ, Biotechnology Advances 37:107412 (2019). The exemplary anti-TL1A antibody pharmaceutical compositions described herein may be lyophilized, aqueous, or frozen.

[0366] Pharmacochemically acceptable carriers are generally non-toxic to the recipient at the dosage and concentration used and include buffers such as histidine, phosphates, citrates, acetates and other organic acids; antioxidants including ascorbic acid and methionine; preservatives (such as octadecyldimethylbenzylammonium chloride; hexamethonium chloride; benzalkonium chloride; benzethonium chloride; phenol, butyl or benzyl alcohol; alkylparabens such as methyl or propylparaben; catechol; resorcinol; cyclohexanol; 3-pentanol; and m-cresol); and low molecular weight (less than approximately 10 residues) porosinate. Lipeptides; proteins such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, histidine, arginine, or lysine; monosaccharides, disaccharides, and other carbohydrates including glucose, mannose, or dextrin; chelating agents such as EDTA; sugars such as sucrose, mannitol, trehalose, or sorbitol; salt-forming counterions such as sodium; metal complexes (e.g., Zn-protein complexes); and / or nonionic surfactants such as polyethylene glycol (PEG).

[0367] The pharmaceutical compositions described herein may also include multiple active ingredients required for the specific indication being treated, preferably those having complementary activities that do not adversely affect one another. Such active ingredients are appropriately combined in amounts effective for the intended purpose.

[0368] Pharmaceutical compositions used for in vivo administration are generally sterile. Sterility can be easily achieved, for example, by filtration through a sterile filtration membrane.

[0369] Anti-TL1A antibodies and their compositions can also be used in combination with other drugs that help enhance and / or complement the efficacy of the drug, or they can be administered separately, simultaneously, or sequentially.

[0370] B. Formulations Therapeutic formulations of anti-TL1A antibodies used in accordance with this disclosure are prepared for storage in the form of lyophilized formulations or aqueous solutions by mixing a protein of the desired purity with any pharmaceutically acceptable carrier, excipient, or stabilizer (Remington, The Science and Practice of Pharmacy 20th Ed. Mack Publishing, 2000). Acceptable carriers, excipients, or stabilizers are nontoxic to the recipient at the dosage and concentration used and include buffers such as phosphates, citrates, and other organic acids; salts such as sodium chloride; antioxidants including ascorbic acid and methionine; preservatives (such as octadecyldimethylbenzylammonium chloride, hexamethonium chloride, benzalkonium chloride, benzethonium chloride, phenol, butyl, or benzyl alcohol, alkylparabens such as methyl or propylparaben, catechol, resorcinol, cyclohexanol, 3-pentanol, and m-cresol); and low molecular weight (less than about 10 residues). Lipeptides; proteins such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, histidine, arginine, or lysine; monosaccharides, disaccharides, and other carbohydrates including glucose, mannose, or dextrin; chelating agents such as EDTA; sugars such as sucrose, mannitol, trehalose, or sorbitol; salt-forming counterions such as sodium; metal complexes (e.g., Zn-protein complexes), and / or nonionic surfactants such as TWEEN®, PLURONICS®, or polyethylene glycol (PEG).

[0371] Liposomes that may contain anti-TL1A antibodies are prepared by methods known in the art, such as those described in Epstein, et al., Proc. Natl. Acad. Sci. USA 82:3688 (1985); Hwang, et al., Proc. Natl. Acad. Sci. USA 77:4030 (1980); and U.S. Patents 4,485,045 and 4,544,545. Liposomes with improved circulation time are disclosed in U.S. Patent 5,013,556. Particularly useful liposomes can be prepared by reverse-phase evaporation using a lipid composition containing phosphatidylcholine, cholesterol, and PEG-derivativeized phosphatidylethanolamine (PEG-PE). Liposomes with the desired diameter are obtained by extruding the liposomes through a filter with a specified pore size.

[0372] The active ingredient may also be encapsulated in microcapsules prepared, for example, by coacervation technology or interfacial polymerization (e.g., hydroxymethylcellulose or gelatin microcapsules and poly(methyl methacrylate) microcapsules, respectively), or encapsulated in colloidal drug delivery systems (e.g., liposomes, albumin microspheres, microemulsions, nanoparticles and nanocapsules) or macroemulsions. Such techniques are disclosed in Remington, The Science and Practice of Pharmacy 20th Ed., Mack Publishing (2000).

[0373] Sustained-release preparations may be prepared. Suitable examples of sustained-release preparations include semipermeable matrices of solid hydrophobic polymers containing antibodies, the matrices of which are in the form of molded articles, e.g., membranes or microcapsules. Examples of sustained-release matrices include polyesters, hydrogels (e.g., poly(2-hydroxyethyl methacrylate) or poly(vinyl alcohol)), polylactide (U.S. Patent No. 3,773,919), copolymers of L-glutamic acid and 7-ethyl-L-glutamic acid, non-degradable ethylene-vinyl acetate, degradable lactic acid-glycolic acid copolymers, LUPRON DEPOT (trademark) (injectable microspheres consisting of lactic acid-glycolic acid copolymer and leuprolide acetate), sucrose acetate isobutyrate, and poly-D-(-)-3-hydroxybutyric acid.

[0374] Preparations used for in vivo administration must be sterile. This can be easily achieved, for example, by filtering through a sterile filtration membrane. The therapeutic anti-TL1A antibody composition is generally placed in a container with a sterile access port, such as an intravenous solution bag or vial with a stopper that can be punctured by a subcutaneous needle.

[0375] The compositions according to this disclosure may be in the form of tablets, pills, capsules, powders, granules, liquids or suspensions, or suppositories, for oral, parenteral or rectal administration, or administration by inhalation or inhalation.

[0376] To prepare solid compositions such as tablets, the main active ingredient is mixed with a pharmaceutical carrier, such as conventional tableting components like corn starch, lactose, sucrose, sorbitol, talc, stearic acid, magnesium stearate, dicalcium phosphate, or gum, and other pharmaceutical diluents, such as water, to form a solid pre-formulation composition containing a homogeneous mixture of the compound of the Disclosure or a non-toxic, pharmaceutically acceptable salt thereof. When these pre-formulation compositions are referred to as homogeneous, it means that the active ingredient is uniformly dispersed throughout the composition so that the composition can be easily subdivided into equally effective unit dosage forms such as tablets, pills, and capsules. This solid pre-formulation composition is then subdivided into the above-mentioned unit dosage forms containing about 0.1 to about 500 mg of the active ingredient of the Disclosure. Tablets or pills of novel compositions can be coated or otherwise formulated to provide a dosage form that offers the advantage of a longer-acting effect. For example, a tablet or pill may contain internal and external dosage components, the latter in the form of an envelope covering the former. The two components can be separated by a single enteric coating, which serves to withstand disintegration in the stomach, allowing the internal components to pass through the duodenum intact or to have their release delayed. Various materials can be used for such enteric coatings or coatings, including numerous polymer acids and mixtures of polymer acids with materials such as shellac, cetyl alcohol, and cellulose acetate.

[0377] Suitable surfactants include nonionic agents such as polyoxyethylene sorbitan (e.g., Tween® 20, 40, 60, 80, or 85) and other sorbitans (e.g., Span® 20, 40, 60, 80, or 85). A composition containing a surfactant may conveniently contain between 0.05 and 5% of the surfactant, and may be between 0.1 and 2.5%. It will be understood that other components, such as mannitol or other pharmaceutically acceptable vehicles, may be added as needed.

[0378] Suitable emulsions can be prepared using commercially available lipid emulsions such as INTRALIPID®, LIPOSYN®, INFONUTROL®, LIPOFUNDIN®, and LIPIPHYSAN®. The active ingredient may be dissolved in a pre-mixed emulsion composition, or in an emulsion formed by mixing oil (e.g., soybean oil, safflower oil, cottonseed oil, sesame oil, corn oil, or almond oil) and phospholipids (e.g., egg phospholipid, soybean phospholipid, or soybean lecithin) with water. It will be understood that other components, such as glycerol or glucose, may be added to adjust the tonicity of the emulsion.

[0379] A suitable emulsion typically contains up to 20% oil, for example, 5–20%. Fatty emulsions can contain fatty droplets of 0.1–1.0 pm, especially 0.1–0.5 pm, and have a pH in the range of 5.5–8.0.

[0380] The emulsion composition may be prepared by mixing an anti-TL1A antibody with Intralipid® or its components (soybean oil, egg phospholipid, glycerol, and water).

[0381] Compositions for inhalation or inhalation include solutions and suspensions in pharmaceutically acceptable aqueous or organic solvents or mixtures thereof, as well as powders. Liquid or solid compositions may contain the above-mentioned suitable pharmaceutically acceptable excipients. In some embodiments, compositions are administered orally or via nasal respiratory routes for topical or systemic effects. Compositions in preferably sterile, pharmaceutically acceptable solvents may be sprayed using gas. Sprayed solutions may be inhaled directly from a spraying device, or the spraying device may be attached to a face mask tent or an intermittent positive airway pressure (CPAP) respirator. Solutions, suspensions, or powder compositions may be administered preferably orally or nasally from a device that delivers the formulation in an appropriate manner.

[0382] In embodiments of the method for treating IBD described herein, such embodiments also include further embodiments of an anti-TL1A antibody for use in the treatment, or further embodiments of the use of an anti-TL1A antibody in the manufacture of a pharmaceutical for use in the treatment. [Examples]

[0383] VII. Examples Example 1. Phase III multicenter double-blind placebo-controlled study to evaluate the efficacy and safety of induction therapy with afimkibart in patients with moderate to severe active ulcerative colitis. The GA45329 study provided in these examples is a phase III, multicenter, double-blind, placebo-controlled treat-through study designed to evaluate the efficacy and safety of induction and maintenance therapy with afimkibart (formerly PF 06480605, RVT-3101, or RO7790121) in patients with moderate to severe active ulcerative colitis (UC). afimkibart is a fully human immunoglobulin G1 (IgG1) monoclonal antibody (mAb) against tumor necrosis factor-like ligand 1A (TL1A). TL1A plays a central role in regulating intestinal mucosal immunity and is involved in the immunological and fibrotic pathways of inflammatory bowel disease (IBD) by binding to its receptor, cell death receptor 3 (DR3) (Shih et al., Clin Pharmacol Drug Dev, 7:1492-1503, 2014; Xu and Huang, Front Immunol, 13:891328, 2022). Binding of afimkibart to TL1A inhibits TL1A binding and signaling to cell death receptor 3 on immune cells, resulting in anti-inflammatory and anti-fibrotic effects.

[0384] The GA45330 study presented in these examples is a phase 3, multicenter, double-blind, placebo-controlled study designed to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of induction therapy with afimkibart compared to placebo in patients with moderate to severe active UC. The study schema for the GA45330 study is shown in Figure 3.

[0385] Treatment options have expanded significantly over the past decade, with the availability of biologics (e.g., anti-tumor necrosis factor (TNF), anti-IL-12 / 23, and anti-integrin molecule mAbs) and small molecule therapies (e.g., Janus kinase (JAK) inhibitors and sphingosine-1-phosphate (S1P) receptor modulators) in addition to conventional therapies. However, a high level of unmet medical need remains for therapies with a better benefit-risk profile that provide sustained control to reduce inflammation and clinical complications and improve the long-term prognosis of patients with UC.

[0386] A. Joint primary objectives and corresponding estimates The primary objective of the GA45329 trial was to evaluate the efficacy of afimkibart in inducing and maintaining clinical remission compared to placebo (Table 4).

[0387] The primary objective of the GA45330 clinical trial was to evaluate the efficacy of afimkibart in inducing clinical remission compared to placebo (Table 5).

[0388] Clinical remission is defined based on the modified Mayo score (mMS) described in Example 5. The statistical inference supporting this assessment targets estimates representing the effect of assignment to a treatment condition (afimkibart vs. placebo; Example 4) on specific outcomes (endpoints) in a population of patients with moderate to severe active UC, as identified by key trial inclusion and exclusion criteria (Example 3). [Table 4] [Table 5]

[0389] As stated in the International Council for Harmonisation (ICH) E9(R1) Addendum on Estimates and Sensitivity Analysis in Clinical Trials (ICH 2020) to the Guidelines on Statistical Principles of Clinical Trials, the availability or interpretation of endpoint measurements may be affected by the occurrence of interventional events (ICEs; ICH 2020) between randomization and endpoint assessment. Strategies for addressing anticipated ICEs are summarized in Table 6. [Table 6]

[0390] Under these strategies, the estimates supporting the first co-primary objective of the GA45329 trial and the primary objective of the GA45330 trial correspond to the treatment effect summarized by the difference between the two proportions: • Percentage of patients from the target population in clinical remission during the successful course of induction therapy after allocation to afimkibart; The same percentage if these patients were instead assigned to a placebo.

[0391] In the GA45329 trial, the estimated co-primary objectives for maintenance are similarly defined.

[0392] A primary analysis of the GA45329 study data provides estimates of these induction and maintenance treatment effects. If both estimates favor afimkibart over placebo and are considered statistically significant, the study is considered positive.

[0393] A primary analysis of the GA45330 study data will yield estimates of the induction effect. If the estimates favor afimkibart over placebo and are considered statistically significant, the study will be considered positive.

[0394] Details of the statistical hypothesis testing are described in Example 6.

[0395] B. Secondary purposes and corresponding endpoints Efficacy is further considered in the secondary objectives described below (see Tables 7-10). Similar to the primary or co-primary objectives, secondary efficacy objectives have corresponding interest estimates representing the effect of comparing the same treatment condition (afimkibart vs. placebo; Example 4) at a specific endpoint using the same strategy within the same overall patient population (Example 3) and for anticipated interventional events (Table 6). These treatment effects are defined in the same manner as those for the primary or co-primary endpoints and are the effect on a binary efficacy endpoint summarized by the difference in afimkibart versus placebo percentages. For other efficacy endpoints, the effect is generally the difference in summary outcome measures, such as the mean score or mean change from baseline score. Further details regarding the evaluation and rating of different efficacy endpoint types are provided in Examples 5 and 6, respectively. [Table 7] [Table 8]

[0396] The TL1A biomarker indicates TNFSF15 haplotype B carrier status (haplotype B carrier vs. haplotype B non-carrier). Patients who are TNFSF15 haplotype B non-carriers may benefit additionally from afimkibart treatment. See Section II(H) above.

[0397] Other secondary objectives of the study (Tables 9 and 10) also consider both efficacy and safety. Safety endpoints refer to summary outcome measures, rather than participant-level outcome variables. [Table 9] [Table 10]

[0398] C. Exploration objectives and endpoints The exploration objectives and corresponding endpoints are described below (Table 11). Estimates for the exploration effectiveness objective are defined similarly to those supporting the primary and secondary objectives. Similar to the safety domain, exploration objectives beyond effectiveness may have endpoints that describe summary outcome measures rather than participant-level outcome variables. [Table 11]

[0399] Example 2. UC Research Design A. Overall design The GA45329 study is a phase III, multicenter, randomized, double-blind, placebo-controlled treat-through study to assess the efficacy and safety of afimkibart in patients with moderate to severe active UC. A schematic diagram of the GA45329 study is shown in Figures 1 and 2A. The GA45329 study includes an induction phase, a maintenance phase, and an optional open-label extension (OLE) phase. The GA45330 study (Figures 2B and 3) includes only the induction phase and an optional OLE phase.

[0400] The study populations for both studies include participants with moderate to severe active UC who have either (1) failed to receive prior conventional treatment (aminosalicylates, corticosteroids and / or immunosuppressants) (referred to in this protocol as "conventional treatment failure") or (2) failed to receive prior advanced treatment including biologics or targeted small molecules such as anti-TNF, anti-IL12 / 23, anti-integrins, S1P receptor modulators, and JAK inhibitors (referred to in this protocol as "advanced treatment failure").

[0401] The approximately 400 total participants in the GA45329 study and the 350 total participants in the GA45330 study were enrolled across clinical trial sites worldwide and represent a balanced representation of participants who have experienced failure of conventional or advanced treatments. Enrollment of participants who have failed three or more advanced treatments (i.e., three treatments, not three classes of treatment) is capped at a maximum of 30% of the total population.

[0402] The GA45329 study has a treat-through design consisting of a screening period of up to 35 days (+7 days) to determine eligibility; a 12-week induction treatment period; a 40-week maintenance treatment period; an optional open-label extension (OLE) treatment period; and a 12-week safety follow-up period after the final dose of the study treatment (consisting of two visits, one at 6 weeks and one at 12 weeks). GA45330 omits the maintenance treatment period. Entry criteria are based on confirmation of moderate to severe active UC during screening, defined as a modified Mayo score (mMS) of 5–9, including an endoscopic subscore (ES) ≥2, as confirmed by central-reading endoscopy (flexible sigmoidoscopy or colonoscopy).

[0403] Eligible participants in the GA45329 study will be randomly assigned to one of the following treatment arms. afimkibart: 500 mg intravenously (IV) at weeks 0, 2, 6, and 10, followed by 450 mg subcutaneously (SC) every four weeks (Q4W) from week 12 to week 52. Placebo: Placebo IV at weeks 0, 2, 6, and 10, followed by placebo SC Q4W from week 12 to week 52.

[0404] Eligible participants in the GA45330 study will be randomly assigned to one of the following treatment arms. • afimkibart: 500 mg intravenously (IV) at weeks 0, 2, 6, and 10. Placebo: Placebo IV at weeks 0, 2, 6, and 10.

[0405] Randomization will be conducted according to a 3:2 allocation ratio, stratified by prior advanced treatment at baseline (yes / no); baseline corticosteroid use (yes / no); and disease severity (mMS 5–6 and mMS 7–9).

[0406] The induction phase (medication during weeks 0-10) assesses the induction of clinical remission, which is measured at week 12. After completion of the induction phase, participants in the GA45329 study will continue SC administration of afimkibart or a matched placebo during the maintenance phase (weeks 12-52) to monitor clinical response and persistence of remission. From week 12 onward, participants who have completed week 12 (in either the GA45329 or GA45330 study) are eligible to enter the OLE phase if their symptoms meet the disease exacerbation criteria. Participants who have not completed the 12-week induction period for any reason will be withdrawn from the blinding procedure and proceed to a mandatory treatment discontinuation / early withdrawal visit, followed by a post-treatment safety follow-up visit.

[0407] Disease exacerbation will continue to be monitored by the principal investigator beyond week 12. Participants who complete all study procedures, including the administration of the study treatment at week 52 (in the GA45329 study), or who meet the criteria for disease exacerbation at any point during the maintenance phase, will have the option to continue in the OLE phase and receive active treatment. Participants in the GA45329 study who discontinued the maintenance phase before week 52 and did not enter the OLE phase will proceed to a mandatory treatment discontinuation / early withdrawal visit, followed by a post-treatment safety follow-up visit.

[0408] The objective of this study is to evaluate the efficacy and safety of afimkibart compared to placebo. Efficacy will be assessed by the primary or joint primary endpoint of clinical remission (defined based on mMS) at week 12 (induction) (in both the GA45329 and GA45330 studies) and week 52 (maintenance) in the GA45329 study.

[0409] The primary or co-primary, secondary, exploratory, safety, PK, PD, immunogenicity, and any other objectives and corresponding endpoints of this study are described in Example 1. Participants will undergo periodic efficacy and safety evaluations.

[0410] The primary or joint primary endpoint and specific secondary efficacy endpoints are based on the components of the mMS: endoscopic subscore (ES), bowel movement frequency subscore (SFS), and rectal bleeding subscore (RBS). These subscores are assessed from centrally read endoscopic findings as well as participant-reported bowel movement frequency and rectal bleeding scores. Participant-reported UC symptoms, as well as bowel urgency and abdominal pain, are collected daily using an electronic diary (eDiary) during the screening and induction phases. During the maintenance phase of the GA45329 study, these patient-reported outcomes (PROs) are collected daily via eDiary. During the OLE phase of either study, participants complete eDiary PROs for at least 7 days prior to each Q3M (every 3 months) study visit in the first year, and prior to each subsequent annual study visit. If disease exacerbation criteria assessment is required in the OLE phase, eDiary PROs are collected at least 7 days prior to the study visit in which the assessment is being performed, and medication frequencies may be adjusted.

[0411] B. Open-label extension period All participants, regardless of whether they were previously randomized to receive afimkibart or placebo during the double-blind period, will have the opportunity to participate in any OLE period of the study with access to and monitoring of afimkibart, provided they meet the specified eligibility criteria. The OLE period schema for the GA45329 study is provided in Figure 2A. The OLE period schema for the GA45330 study is provided in Figure 2B.

[0412] i. Eligibility criteria for the open extension period Participants are eligible to enter OLE after giving their consent to participate, and the safety of participants is not at risk by continuing to participate in any OLE phase of the study, as assessed by the principal investigator.

[0413] Participants may be eligible to enter OLE at the following points: • If a participant meets the disease exacerbation criteria (see below), at any point after the completion of the 12-week induction period and upon completion of the first dose of the 12-week evaluation and maintenance period. Participants are not eligible for the OLE period before week 12. • In the GA45329 study, assessments were conducted after the completion of the 40-week maintenance phase and at the completion of the 52-week evaluation.

[0414] ii. Criteria for disease exacerbation Participants who, starting after the 12-week evaluation (and the first dose of maintenance therapy in the GA45329 study), have not improved or have worsened compared to baseline (day 1 of week 0), based on investigator assessment, may be eligible to enroll in OLE if they meet both of the following criteria: • ES ≥ 2, based on central reading. • Endoscopic evaluation is required to confirm OLE eligibility for participants discontinuing the double-blind maintenance phase before week 52, and should be performed if UC symptoms appear. However, if performed within the last 6 weeks, the procedure does not need to be repeated. Rectal bleeding score ≥ 2 for at least 3 days within the past 7 days, excluding any day when bowel preparation and endoscopy coincide.

[0415] The achievement of these criteria is captured by efficacy assessment, i.e., endoscopy and rectal bleeding assessment under the Mayo Score (Example 5). In assessing disease exacerbation or potential differential diagnosis, the presence of intestinal pathogens should be ruled out by stool culture / susceptible oocyte and parasite assessment, which should include a C. difficile test. If CMV infection is suspected, a tissue biopsy should be performed.

[0416] For participants who experience symptoms of disease exacerbation only during the OLE period, the principal investigator may, at their discretion, decide to modify the OLE dose schedule, including the need for an unscheduled endoscopy. If the principal investigator decides to discontinue such an endoscopy in assessing disease exacerbation during OLE, it is permissible to apply a symptomatic criterion (rectal bleeding score) in conjunction with another objective criterion of fecal calprotectin ≥ 150 μg / g, in accordance with the American Gastroenterological Association Guidelines (Singh et al., Gastroenterology, 164(3):344-372, 2023).

[0417] iii. Open-label extended dose schedule After week 12 (for example, during the maintenance phase of the GA45329 study), if a participant's symptoms meet the disease exacerbation criteria provided above, the participant may either enter a two-week dose escalation schedule of OLE every two weeks (Q2W) over 12 weeks (450 mg SC Q2W) or withdraw from the study as assessed by the investigator. Participants following the Q2W dose schedule will have the opportunity to reduce to a 450 mg SC Q4W dose schedule after 12 weeks or withdraw from the study as assessed by the investigator (Figures 2A and 2B).

[0418] Participants who complete the 52-week study in the GA45329 study or the 12-week study in the GA45330 study and transition to the OLE phase will continue on the Q4W dose schedule (450 mg SC Q4W). The first OLE visit is at week 56 in the GA45329 study. Participants will continue on the Q4W dose regimen throughout the OLE phase until the end of the study. However, if a participant's symptoms meet the disease exacerbation criteria at any point during the OLE phase, the investigator will assess the options of increasing the dose to 450 mg SC Q2W or discontinuing the study. Participants following the 450 mg SC Q2W dose schedule may reduce their dose to the 450 mg SC Q4W schedule after 12 weeks or discontinue the study as assessed by the investigator. Afimkibart should be administered at least 7 days apart. A maximum of two dose increases to Q2W are permitted during the OLE phase of the study.

[0419] Table 12 shows the medication schedule for the OLE period. [Table 12] DWC = Disease worsening criteria; Early With = Early withdrawal; FU = Follow-up; NA = Not applicable; OLE = Open-label extension period; Q2W = Every 2 weeks; Q4W = Every 4 weeks; SFU = Safety follow-up; Tx Disc = Treatment discontinuation; W = Week. Note: During the OLE phase of the study, a maximum of two dose increases (medication at Q4W → medication at Q2W) are permitted. a The decision to reduce the study to Q4W or to discontinue the participant's study is at the discretion of the principal investigator.

[0420] C. Definition of study completion and duration of participation Participants are considered to have completed the study if they have completed all periods of the study, including their final hospital visit.

[0421] The end of a GA45329 or GA45330 study is defined as the later of the date of the last visit of the last participant in the study, or the date on which the last data point required for statistical analysis, safety follow-up, or statistical analysis follow-up was received from the last participant.

[0422] The GA45329 study is expected to conclude approximately 70 weeks after the last participant was enrolled.

[0423] In the GA45329 study, the total maximum duration of study participation for individuals is expected to be approximately 70 weeks without OLE participation. With OLE participation, treatment may be continued for approximately 5 years, whichever comes first, after the last participant is enrolled in the study or until afimkibart is commercially available in the region.

[0424] The GA45330 study is expected to conclude approximately 30 weeks after the last participant is enrolled.

[0425] In the GA45330 study, the total maximum duration of study participation per individual is expected to be approximately 30 weeks without OLE participation. With OLE participation, treatment may be continued for approximately 5 years, whichever comes first, after the last participant is enrolled in the study or until afimkibart is commercially available in the region.

[0426] Example 3. UC Research Group During the global registration period for the GA45329 study, approximately 400 participants with UC will be enrolled. During the global registration period for the GA45330 study, approximately 350 participants with UC will be enrolled. The inclusion and exclusion criteria applicable to both studies are provided below.

[0427] A. Inclusion criteria Participants are eligible to be included in the GA45329 study and / or GA45330 study only if they meet all of the following criteria:

[0428] i.General inclusion criteria • Age ≥ 18 to ≤ 80 years. Patients aged 16 to under 18 years in Tanner Stage 5 (final adult stage) may be eligible to participate in the study if locally permitted (e.g., permitted by local guidelines and regulations). See Marshall and Tanner, Arch Dis Childh., 44(291), 1969 and Marshall and Tanner, Arch Dis Childh., 45(13), 1970. • Weight ≥ 40kg.

[0429] ii. Ulcerative colitis-specific inclusion criteria Definitive diagnosis of ulcerative colitis (UC) with supportive clinical, endoscopic, and histopathological findings. • Active UC confirmed by endoscopy extending ≥15 cm from the anal margin (flexible sigmoidoscopy or colonoscopy). Participants with proctitis only at baseline (inflammation in the smallest area 5 cm proximal to the anal margin) will be capped at 10% of the total enrollment. • Defined as a 5-9 point mMS including 2 or 3 Mayo Endoscopy Scores (ES) confirmed by a centrally read endoscopy (independent of the study; “Standard Care (SOC) Endoscopy”) performed either (i) during the screening period or (ii) before the screening period in patients with moderate to severe active UC, within 4 weeks of randomization, and with an already established UC diagnosis. If performed before screening, the SOC endoscopy must be video-recorded and in a format suitable for central reading. Participants must not have started any new medications between the SOC endoscopy and randomization. All UC concomitant medications must be stabilized prior to the SOC endoscopy. • Screening for colorectal cancer (CRC) in all participants (conducted according to local standards). Patients with extensive colitis or pancolitis lasting more than 8 years, or left-sided colitis lasting more than 12 years, must undergo surveillance colonoscopy within 12 months prior to screening. All other patients must undergo regular CRC monitoring (according to CRC risk and local standards). Adenomatous polyps must be completely removed according to routine practice before the first dose of the study drug.

[0430] iii. Reproductive inclusion criteria • For female participants of potential pregnancy: consent to abstain from sexual intercourse (refraining from heterosexual intercourse) or to use appropriate contraception, as well as consent to refrain from egg donation or undergo fertility treatment during the treatment period and for 95 days after the last dose of afimkibart. • For male participants: consent to abstain from sex (refraining from heterosexual intercourse) or to use condoms, and consent to refrain from donating sperm.

[0431] iv. Inclusion criteria for previous medications Participants enrolled in the GA45329 or GA45330 study must have previously received at least one of the following treatments and have had an inadequate response, loss of response, and / or intolerance:

[0432] An inadequate response is defined as having persistent signs and symptoms of active disease despite completing at least one approved medication regimen as indicated on the product label.

[0433] Intolerances may include, but are not limited to, infusion-related reactions, injection site reactions, rashes, serum sickness, liver abnormalities, demyelination, congestive heart failure, and infections. If a potential participant is determined to be intolerant to a previous treatment, there are no minimum dose or duration requirements.

[0434] Loss of response is defined as a recurrence of signs and symptoms of active disease during approved treatment after prior clinical benefit (discontinuation despite clinical benefit is not considered a failure or intolerance of advanced UC treatment).

[0435] The medications used to certify participants in this category, including biosimilars, must be approved for the treatment of UC. Participants who have previously been exposed to investigational treatments for UC must still meet the inclusion criteria of "conventional treatment failure" or "advanced treatment failure."

[0436] Conventional treatment failures Steroids (e.g., systemic prednisone, oral budesonide). The following definitions are used as guidelines for the use of corticosteroids in clinical trials. ○ Corticosteroid refractory: Persistent active disease despite treatment with at least one 4-week induction regimen including an initiating dose of ≥20 mg oral prednisone (or equivalent) for at least 2 weeks or ≥5 days of IV prednisone, or persistent active disease after at least 4 weeks of oral budesonide at 9 mg / day. ○ Corticosteroid dependence: (i) Inability to reduce steroid dosage to less than the equivalent dose of 10 mg / day of prednisolone within 3 months of starting steroids without relapsing active disease, or (ii) Relapse within 3 months of discontinuing steroids. ○ Corticosteroid intolerance: A history of corticosteroid intolerance (including, but not limited to, Cushing's syndrome, osteopenia / osteoporosis, hyperglycemia, insomnia, and infections). • Immunomodulatory drugs for at least 12 weeks, which may include: ○ Oral azathioprine (AZA) ≥ 1.5 mg / kg / day (or according to local standard care (SOC)). ○ Oral 6-mercaptopurine (6-MP) ≥ 0.75 mg / kg / day (or according to local SOC). ○ Intramuscular or SC methotrexate (MTX) at a dose of ≥15 mg / week. ○ During at least one 12-week regimen of oral AZA or 6-MP at a stable or increasing dose, ≥230 pmol / 8x10 8 Persistent signs and symptoms of active disease despite RBC 6-TG levels. ○ A history of intolerance to AZA, 6-MP, or MTX (but not limited to, including nausea / vomiting, abdominal pain, pancreatitis, LFT abnormalities, lymphopenia, TPMT gene mutations, and infections). • Oral aminosalicylates for at least 4 weeks, including the following minimum doses: ○ 2.4g / day of mesalamine (or according to local SOC) ○ 4.0g / day of sulfasalazine (or as per local SOC) ○ 1.0g / day of olsalazine (or according to local SOC) ○ 6.75g / day of balsaradide (or according to local SOC)

[0437] The conventional treatment failure population also includes patients who previously received advanced treatment (biologics or small molecules) but discontinued treatment for reasons other than failure (e.g., changes in coverage, well-controlled disease).

[0438] Failure of advanced treatments • Antitumor necrosis factor (TNF) agents, including but not limited to: ○ At least one 6-week induction regimen of infliximab (≥5 mg / kg IV or as per local labeling at 0, 2, and 6 weeks) or a biosimilar of its equivalent. ○ At least one 8-week induction regimen of adalimumab (a single 160 mg SC dose followed by a single 80 mg SC dose (or a single 80 mg SC dose in countries where this dosing regimen is permitted), followed by a single 40 mg SC dose at least two weeks apart, or as per local labeling) or a biosimilar of its equivalent. ○ At least one 2-week induction regimen of golimumab (one 200 mg SC dose followed by one 100 mg SC dose, at least 2 weeks apart, or as per local labeling). • Antiintegrins including, but not limited to, the following: ○ At least one 6-week induction regimen of vedolizumab (300 mg IV at 0, 2, and 6 weeks, or as per local labeling). • Not limited to, but including anti-IL12 / IL23: ○ A single IV dose (single weight-based dose) using ustekinumab (260 mg for participants weighing ≤55 kg; 390 mg for participants weighing >55 kg to ≤85 kg; 520 mg for participants weighing >85 kg or as per local labeling) or an equivalent biosimilar induction regimen of at least one 8-week induction regimen. ○ At least one 8-week regimen of mirikizumab (300 mg IV at weeks 0, 4, and 8, or as per local labeling). ○ At least one 8-week induction regimen of risukizumab (1200 mg IV or as per local labeling at weeks 0, 4, and 8). ○ At least one 8-week induction regimen of guselkumab (200 mg IV or as per local labeling at weeks 0, 4, and 8). Janus kinase (JAK) inhibitors, including but not limited to: ○ At least one 8-week induction course with upadacitinib (45 mg orally daily, or as per local labeling). ○ At least one 8-week induction course of tofacitinib (10 mg orally twice daily as immediate-release tablets or 22 mg orally once daily as extended-release tablets or as per local labeling). • Sphingosine-1-phosphate (S1P) receptor modulators, including but not limited to: ○At least one 10-week induction course of ozanimod (0.92 mg orally daily). ○ At least one 12-week induction course of etrasimodo (2 mg orally daily).

[0439] B. Exclusion criteria Potential participants will be excluded from the study if any of the following criteria apply:

[0440] i. Inflammatory bowel disease exclusion criteria • Severe UC as demonstrated by any of the following: ○ You are likely to require hospitalization for treatment of UC within 2 weeks prior to screening, or, at the physician's discretion, hospitalization for any type of medical care or surgical intervention (e.g., colectomy) for UC during the study. ○ Fulminant colitis, toxic megacolon, or a recent (within the last 6 months) history of toxic megacolon, or current evidence of bowel perforation. ○ Previous extensive colectomy, subtotal or total colectomy, or planned surgery for UC under investigation. Current diagnosis of Crohn's disease (CD), abdominal / intraperitoneal / perianal fistula and / or abscess, undetermined colitis, unclassified IBD, microscopic colitis, ischemic colitis, infectious colitis, radiation colitis, or active diverticular disease. • Presence of a stoma or ileosal pouch. • Current diagnosis or suspicion of primary sclerosing cholangitis.

[0441] ii. Exclusion criteria based on medical history • Lack of peripheral venous access. • Major surgery performed within 6 weeks prior to screening or major surgery planned during the study.

[0442] • In the opinion of the principal investigator, any significant uncontrolled medical comorbidities (such as heart, lung, kidney, liver, or gastrointestinal disorders (excluding UC)), psychiatric conditions, or other conditions that would interfere with the study results, impair patient safety, or hinder the potential participant from providing informed consent or complying with the study procedures. • Pregnant or breastfeeding, or intending to become pregnant during the study or within 95 days of the last dose of afimkibart. Any conditions that make endoscopic assessment impossible. • Past or present evidence that a clear low-grade or high-grade colonic dysplasia, adenoma, or neoplasm has not been completely removed. A history of malignant tumors within the five years prior to the screening visit, excluding malignant tumors that were appropriately treated by resection of non-metastatic basal cell carcinoma, squamous cell carcinoma, or in situ cervical cancer. • A history of alcohol, drug, or chemical abuse within the year prior to screening. • History of blood transfusions within 30 days prior to screening.

[0443] iii. Exclusion criteria for infection or risk of infection • Clinically significant infections that have not recovered and / or required hospitalization and / or IV antibiotics within four weeks prior to randomization. Clinically significant infections that were essentially opportunistic are not acceptable within three months prior to randomization. Evidence or treatment of Clostridioides difficile (C. difficile; formerly known as Clostridium difficile) as assessed by the detection of C. difficile toxin within 30 days prior to randomization (week 0, day 1), or by the detection of other enteropathogens (by fecal culture / susceptibility assessment and assessment of eggs and parasites) within 30 days prior to randomization (week 0, day 1). • Any diagnosis of cytomegalovirus (CMV) colitis within the past 30 days (including diagnoses during screening). Laboratory confirmation of CMV from colon biopsy samples during screening assessment is required only if there is a high clinical suspicion and to determine the need for CMV treatment. • Confirmation of HIV infection during screening (e.g., positive HIV test). • A positive test result for hepatitis B infection at screening, defined as meeting either of the following criteria: (i) a positive hepatitis B surface antigen (HbsAg) test at screening, and (ii) quantitative HBV DNA exceeding the lower limit of quantification in patients who are negative for the hepatitis B surface antibody (HbsAb) test and positive for the whole hepatitis B core antibody (HbcAb) test. • The hepatitis C virus (HCV) antibody test during screening was positive. • Positive for tuberculosis (TB) during or within 3 months prior to screening (defined as positive by the QuantiFERON® TB-Gold Test (QFT), or, if QFT is not available, by a purified protein derivative (PPD) skin test or other locally approved TB enzyme-linked immunosorbent assay (ELISA) test (e.g., T-SPOT®) as per local guidelines or regulations, except as follows): (i) Bacillus with a positive PPD skin test (ii) Potential participants with a history of Calmette-Guerin (BCG) vaccination will not be excluded if they have a negative QFT at the time of screening; and (ii) Potential participants with a positive or indeterminate QFT and participants without a history of BCG vaccination with a positive PPD skin test will not be excluded if they meet all of the following criteria: no symptoms consistent with TB, a recorded history of a completed course of appropriate prophylaxis in accordance with local standard care prior to randomization (week 0, day 1) (completion of treatment for latent TB), no known exposure to a case of active TB after most recent prophylaxis, and no evidence of active TB on chest X-ray performed during or within 3 months prior to screening. • Organ transplant history. • Acquired or congenital immunodeficiency.

[0444] iv. Exclusion Criteria for Clinical Laboratory Results • In the opinion of the principal investigator, clinically significant abnormalities in laboratory tests during screening (hematology, serological chemistry, and urinalysis) could pose an additional risk when administering the study procedure to potential participants. • ALT, AST, or ALP levels are 2.5 times or greater than the upper limit of normal (ULN), total bilirubin levels are 1.5 times or greater than ULN, or there is an abnormality in a synthetic liver function test that the investigator deems clinically important. Patients with an established diagnosis of Gilbert's syndrome (i.e., documented necessary sources showing unconjugated hyperbilirubinemia without evidence of hemolysis) with total bilirubin levels less than 3 × ULN may be included.

[0445] ANC<1.5x109 / L (1500 / μL), with one exception: participants with recorded benign ethnic neutropenia (BEN): ANC < 1.3 × 10 9 / L (1300 / μL). ·Platelet count <100,000μL. • Hemoglobin <8 g / dL. • Absolute lymphocyte count < 500 / μL. • Estimated glomerular filtration rate (eGFR) < 30 mL / min / 1.73 m² 2 .

[0446] v. Exclusion Criteria for Prohibited Drugs Prohibited medications are any of the following related to past or current treatments: • Approved UC treatment, including approved oral small molecule (e.g., S1P receptor modulators, JAK inhibitors) treatment within two weeks prior to screening endoscopy (or SOC endoscopy), or use of an approved biological agent within eight weeks prior to randomization (week 0, day 1) or within five half-lives, whichever is longer. If there is a proper record of undetectable drug levels measured by a commercially available assay for any of the approved biological agents, there is no minimum washout prior to randomization (week 0, day 1). • Use of investigational or experimental treatments within approximately 30 days for non-biological treatments, or within 8 weeks for biological treatments, or within 5 half-lives prior to randomization (week 0, day 1) (whichever is longer). • Any immunosuppressive treatment, including B-cell depletion agents (e.g., natalizumab, rituximab) or other lymphocyte depletion agents (e.g., alemtuzumab), or any other immunosuppressant (e.g., those for which live vaccines are contraindicated), received within one year prior to screening or intended to be received during the study. • No administration of oral prednisone >20 mg / day within two weeks prior to screening endoscopy (or SOC endoscopy), or any intention to receive a stable dose of prednisone ≤20 mg for more than two weeks prior to screening endoscopy (or SOC endoscopy) during the study. Treatment with IV corticosteroids intended to be received ≤2 weeks prior to or during a screening endoscopy (or SOC endoscopy), with the exception of a single dose of IV steroids for managing potential infusion-related reactions (IRRs). • The presence of non-UC symptoms (e.g., uncontrolled asthma) that may require treatment with >20 mg / day of prednisone (or equivalent) during the course of the study. Treatment with corticosteroid enemas or suppositories and / or topical (rectal) 5-aminoalicyclic acid (5-ASA) preparations within 2 weeks prior to or during the study of a screening endoscopy (or SOC endoscopy). Treatment with topical rectal herbal medicines (e.g., Chinese medicine), herbal enemas, or suppositories intended to be received within 2 weeks prior to or during a screening endoscopy (or SOC endoscopy). Treatment with an approved oral traditional medicine (e.g., Chinese medicine) intended to be received within 4 weeks prior to or during a screening endoscopy (or SOC endoscopy). • Transplant / stem cell therapy intended to be received at any point before randomization (week 0, day 1) or during the study. Treatments involving cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil intended to be received ≤ 16 weeks prior to randomization (week 0, day 1) or during the study. • Apheresis intended to be received within 2 weeks prior to or during the study of a screening endoscopy (or SOC endoscopy). • The participant must have received a fecal microbiota transplant within four weeks prior to randomization (week 0, day 1). • Known exposure to anti-TL1A (afimkibart (RVT-3101) / PF-06480605) or any type of anti-TL1A treatment. • Patients must receive a live or attenuated vaccine within 4 weeks prior to the screening endoscopy (or SOC endoscopy), or intend to receive one during the study; the use of non-live (inactivated) vaccines is permitted. Chronic (e.g., >7 days) use of nonsteroidal anti-inflammatory drugs (NSAIDs); occasional use of NSAIDs and acetaminophen is acceptable (e.g., for headache, arthritis, myalgia, or menstrual cramps). Aspirin ≤325 mg / day is acceptable. • Treatment with immunoglobulin or blood products within four weeks prior to screening, or any condition that would likely necessitate such treatment during the course of the study. • IV antibiotics administered for ≤4 weeks prior to randomization (week 0, day 1). • Previous severe allergic reaction (NCI CTCAE v5.0 grade 3 or higher) or anaphylactic reaction to any excipient of a biological or research drug.

[0447] Example 4. UC study procedures, other procedures related to the study design, and concomitant therapies In the GA45329 and GA45330 studies, afimkibart (500 mg) or placebo was administered intravenously (IV) at weeks 0, 2, 6, and 10 (induction phase). In the GA45329 study, afimkibart (450 mg) or placebo was then administered subcutaneously (SC) every four weeks (Q4W) from week 12 to week 52 (maintenance phase). The maintenance phase was omitted in the GA45330 study. In the open-label extension phase of both studies, afimkibart was administered every two weeks (Q2W) at either 450 mg SC Q4W or 450 mg SC. Changes in study drug doses were not permitted during the double-blind phase of the studies. However, dose increases or decreases (from Q4W to Q2W or from Q2W to Q4W, respectively) may be permitted during the OLE phase. Other dosing frequencies (e.g., weekly dosing) were not permitted.

[0448] Table 13 provides a description of the assigned research procedures for studies GA45329 and GA45330. [Table 13]

[0449] Intravenous administration of afimkibart should be performed under supervision with trained personnel to manage potentially serious reactions and with immediate access to appropriate equipment and medications.

[0450] In applicable facilities, SC research procedures during the OLE period may be administered by trained nursing professionals at the participant's home or another appropriate location (mobile nursing (MN) visit). MN administration is available after the first Q3M visit in the first year of the OLE period.

[0451] IV infusion takes 60 (±10) minutes to deliver. The post-administration observation period for IV infusion is 60 minutes.

[0452] For participants experiencing an infusion-related reaction (IRR), subsequent infusions may be performed in accordance with institutional / local clinical guidelines or IRR management guidelines, including, for example, slowing the infusion rate, interrupting the infusion, and / or administering premedication (which may include acetaminophen (or paracetamol), an antihistamine (e.g., diphenhydramine), and / or a single dose of IV corticosteroid).

[0453] The post-administration observation period for SC injection is 30 minutes, except for the first 12 weeks of the OLE period, which have a post-administration observation period of at least 60 minutes. Visits during the first 12 weeks of OLE are not eligible for MN; i.e., the first three doses for participants after the Q4W administration regimen and the first six doses for participants after the Q2W administration regimen are not eligible for MN.

[0454] A. Assignment of treatment GA45329 and GA45330 are randomized, double-blind studies. In each study, participants are randomly assigned to one of two treatment arms: afimkibart or placebo. Randomization is performed in a 3:2 ratio through the use of permutation block randomization to ensure a balanced assignment to each treatment arm. Randomization is stratified by advanced UC treatment experience (naive or prior exposure to biologics, S1P receptor modulators, or JAK inhibitors), baseline corticosteroid use, and baseline disease activity (moderate, defined as mMS 5 or 6, or severe, defined as mMS 7–9).

[0455] B. Change of dosage Changes to the study drug dosage are not permitted during the double-blind period of the study. However, dose increases or decreases (from Q4W to Q2W or Q2W to Q4W, respectively) may be permitted during the OLE period. Other dosing frequencies (e.g., weekly dosing) are not permitted.

[0456] C. Combination therapy Table 14 outlines permitted and prohibited concomitant therapies for UC. Table 15 outlines permitted and prohibited concomitant therapies not related to UC. Concomitant drug restrictions apply to all phases of the study, including the OLE phase. In general, the principal investigator may manage the care of participants (including pre-existing conditions) by using supportive care as clinically directed and in accordance with local standard practice, except for prohibited therapies as defined in Tables 14 and 15. [Table 14] TIFF2026527426000021.tif471705-ASA=5-aminosalicylic acid;6-MP=6-mercaptopurine;AZA=azathioprine;IRR=infusion-related reaction;JAK=Janus kinase;MMX=multimatrix;MTX=methotrexate;NA=not applicable;S1P=sphingosine-1-phosphate;SOC=standard care;TL1A=tumor necrosis factor-like ligand 1A;TNF=tumor necrosis factor;UC=ulcerative colitis. [Table 15]

[0457] D. Corticosteroid tapering During the 12-week induction period in both studies, participants will maintain a stable baseline corticosteroid dose.

[0458] In the GA45329 study, after the 12-week evaluation, participants began corticosteroid tapering during the maintenance phase.

[0459] In the GA45330 study, after the 12-week evaluation, and at the discretion of the principal investigator, participants will begin corticosteroid tapering within the first 12 weeks of entering the open-label extension phase.

[0460] Table 16 shows the recommended tapering schedule for oral corticosteroids. [Table 16]

[0461] For participants who cannot tolerate corticosteroid tapering without a relapse of UC clinical symptoms or steroid withdrawal, the corticosteroid dose may be increased during the study (up to the dose at trial entry, if necessary), but tapering should be restarted within two weeks.

[0462] Example 5. Evaluation and Procedure of UC Study A. Effectiveness Evaluation The GA45329 and GA45330 studies will complete the patient-reported outcome (PRO) and clinician-reported outcome (ClinRO) devices to evaluate the treatment benefits of afimkibart. Furthermore, the PRO devices will allow for the supplementation of each participant's direct experience with afimkibart. PRO data are summarized in Table 17 and collected by the devices described below.

[0463] In the GA45329 study, the efficacy evaluation at week 12 should be completed before the first week of administration of the SC study treatment during the maintenance phase.

[0464] In the GA45330 study, the efficacy evaluation at week 12 should be completed before the first week of administration of the SC study treatment during the OLE phase. [Table 17] a This patient-reporting device is used to assess health economics rather than efficacy.

[0465] i. Mayo score Variants of the Mayo Score are assessed at a designated time as a composite based on up to four assessments, which are described in more detail below: bowel movement frequency subscore (SFS), rectal bleeding subscore (RFS), physician's global assessment (PGA), and endoscopy subscore (ES). Each of these assessments has a scoring range of 0 to 3, with higher values ​​indicating greater severity.

[0466] The composite score variant is defined as follows: • Mayo score (MS): Sum of all four subcores (range 0-12). • Modified Mayo Score (mMS): Sum of SFS, RBS, and ES (range 0-9). • Partial Mayo Score (pMS): Sum of SFS, RBS, and PGA (range 0-9). • Partially Modified Mayo Score (pmMS): Sum of SFS and RBS (range 0-6).

[0467] Throughout, ES is defined to be in line with a modified scoring system in which the presence of any degree of wear must correspond to at least two subscores.

[0468] ia. Frequency of bowel movements and rectal bleeding Bowel movement frequency and rectal bleeding are single-item self-report assessments, both scored on a 4-point Likert scale with a 24-hour recall period. Bowel movement frequency assesses the number of times a patient goes to the toilet with a bowel movement or the passage of blood and / or mucus, relative to their usual frequency. Rectal bleeding assesses the most severe amount of blood passing through the rectum during these toilet visits.

[0469] The "normal" reference for bowel movement frequency corresponds to the number of stools during a 24-hour period of remission, or (if the disease has never been in remission) before the first onset of signs and symptoms of UC leading to a UC diagnosis. This number is recorded for each participant in the screening.

[0470] The corresponding subscores (SFS and RBS, respectively) are calculated as the average over the 7 days prior to the relevant point in time.

[0471] SFS is quantified as follows: Under the baseline, as defined, for each individual participant: 0 = Normal number of stool samples for this patient. 1 = 1-2 more flights than usual. 2 = 3-4 more flights than usual. 3 = 5 or more flights than usual.

[0472] RBS is quantified as follows: This represents the worst rectal bleeding observed by participants on that day: 0 = No blood is observed, or there is no bowel movement. 1 = Stool with blood lines. 2 = Stool with blood exceeding the line. 3 = Only blood passes through.

[0473] Overall evaluation by physicians The subscores reported for PGA should reflect the clinician's assessment of the participant's current overall condition and should take into account other criteria, including the patient's daily abdominal discomfort, overall well-being, physical examination findings, and performance status (Schroeder et al., NEJM, 317(26):1625-1629, 1987).

[0474] PGA is quantified as follows: 0=normal 1 = Mild 2=moderate 3=severe

[0475] IC Endoscopy All participants will undergo either a colonoscopy or flexible sigmoidoscopy during a designated visit or as part of the SOC (unrelated to the study if performed before the screening period). At screening, the scope and timing requirements for endoscopic evaluation will be determined by UC-specific study inclusion criteria.

[0476] ES should reflect the worst mucosal appearance during flexible sigmoidoscopy or colonoscopy on a 4-point scale. Consistent with regulatory guidelines, this scale excludes mild abrasion from features ES=1. Abrasion evident on video recordings should be reported as ES≧2. ES, rated by blinded central readout, should be used to determine inclusion criteria, efficacy endpoints, and disease progression criteria.

[0477] A biopsy sample is collected while the endoscope is withdrawn from the intestine.

[0478] ES is quantified as follows: 0 = Normal appearance of the mucous membrane. 1 = Mild disease (erythema, decreased vascular pattern, no abrasion). 2 = Moderate disease (marked erythema, no vascular pattern, degree of abrasion, erosion). 3 = Severe illness (spontaneous bleeding, ulcer).

[0479] ii. Geboes Grading Scale The Geboes Grading Scale is a seven-item classification system for assessing the histological activity of ulcerative colitis (UC), with items categorized from the least severe to the most severe features of inflammation. (Geboes et al., Gut, 47:404-409, 2000). Each grade is assigned a subgrade ranging from 0 to 3 or 4, with higher values ​​indicating greater severity of the corresponding feature.

[0480] Grading is performed by central readout using slide images processed from colon biopsies taken during endoscopy at designated visits.

[0481] iii. The urgency of the intestines The bowel urgency is a single-item self-report assessment of the need for a sudden or immediate bowel movement within the past 24 hours. Item responses are reported on a 4-point Likert scale ranging from "none" to "severe."

[0482] iv.Abdominal pain Abdominal pain is a single-item self-report assessment of the severity of abdominal pain experienced over the past 24 hours. Item responses are reported on a 4-point Likert scale ranging from "none" to "severe." v.Functional Assessment of Chronic Illness Therapy-Fatigue

[0483] The Functional Assessment of Chronic Illness-Fatigue (FACIT-F; version 4) is a 13-item self-report assessment of fatigue. FACIT-F has been validated for use in a variety of conditions, including anemia and IBD (Yellen et al., J Pain Symptom Manage, 13:63-74, 1997; Cella et al., J Rheum, 32:811-819, 2005; Lai et al., J Rheumatol, 38:672-679, 2011; Tinsley et al., Aliment Pharmacol Ther, 34:1328-1336, 2011; Acaster et al., Health Qual Life Outcomes, 13:60, 2015). Each item response option indicates the extent to which a given description of the level or impact of fatigue has applied over the past seven days. Response options are graded on a 5-point Likert-type scale, ranging from "none at all" to "very many."

[0484] vi. Inflammatory Bowel Disease Questionnaire The Inflammatory Bowel Disease Questionnaire (IBDQ) is a validated, self-report, 32-item assessment of health-related quality of life in patients with IBD (Guyatt et al., Gastroenterology, 96:80410, 1989; Irvine, J Pediatr Gastroenterol Nutr, 28:S23-S27, 1999). The IBDQ covers four domains: bowel symptoms (10 questions); systemic symptoms, including sleep disturbances and fatigue (5 questions); affective functioning, such as depression, aggression, and agitation (12 questions); and social functioning, which refers to the ability to participate in social activities and work (5 questions). Each question has a recall period of the past two weeks. Response options are graded on a 7-point Likert-type scale.

[0485] vii. Impressions of overall changes in the patient The Patient's Overall Change Perception (PGIC) is a single-item self-report assessment of the overall change in UC symptoms from the start of the study to the present. Item responses are reported on a 5-point Likert-type scale ranging from "quite bad" to "better."

[0486] viii. Impression of the overall severity of the patient's condition The Patient's Overall Severity Impression (PGIS) is a single-item self-report assessment of the overall severity of UC symptoms. Item responses are reported on a 6-point Likert scale ranging from "none" to "very severe."

[0487] B. Biomarker evaluation The following biomarker samples will be collected from patients and participants screened at all pre- and post-treatment points in all sites, where applicable: Blood samples can be collected from all screened patients to determine TL1A biomarker status, and nucleic acids can be used to evaluate predictive biomarkers and support the potential development of diagnostic and other biomarker assays. • To evaluate PD biomarkers, peripheral blood is collected, processed, and total sTL1A levels are assessed. Non-invasive biomarker measurements of hsCRP and fecal calprotectin will be performed using peripheral blood and stool samples, respectively. • Collect exploratory peripheral blood, serum, and stool samples to measure other biomarkers and pathophysiological biomarkers of the TL1A pathway. Methods may include, but are not limited to, RNA sequencing, immunoassays, mass spectrometry, and PCR. Colon biopsy tissue is collected at designated endoscopy visits, including whether an endoscopy was performed prior to screening as part of the SOC. These colon biopsies are used for exploratory biomarker determination, which may include, but is not limited to, evaluation of local PD biomarkers, TL1A pathway biomarkers, drug exposures, and pathophysiological biomarkers related to inflammation and histology. These evaluations may include RNA sequencing, immunoassays, IHC, mass spectrometry, PCR, and spatial imaging.

[0488] Exploratory biomarker studies include, but are not limited to, cytokines / chemokines, target and pathway proteins or genes, inflammatory genes or proteins, the microbiome and its products in blood, serum or plasma, stool, and mucosal tissue. Genomic studies may include germline variant exploration. Genomic profiling may include whole-genome sequencing (WGS) or whole-exome sequencing (WES) of blood samples.

[0489] Biomarkers are evaluated at baseline and at subsequent points in time after administration of afimkibart or a matched placebo. Baseline or longitudinal biomarker levels may be compared to efficacy, other biomarkers, imaging, or safety measures to assess prognostic or predictive properties. Biomarkers may also be analyzed longitudinally as absolute values ​​and / or percentage changes relative to baseline over time and may be compared to efficacy, PK, other biomarkers, or safety measures to determine PD properties. Exploratory biomarker analyses may include prognostic, predictive, and PD biomarker analyses from DNA / RNA-based assays. Any remaining plasma and / or serum after PK or immunogenicity analysis is complete may be used for the exploratory biomarker studies described above.

[0490] To determine variants of the TL1A biomarker, essential blood samples for DNA isolation are collected from consenting participants during screening.

[0491] C. Questionnaire on Labor Productivity and Activity Impairment: Ulcerative Colitis Work Productivity and Activity Impairment Questionnaire: The Ulcerative Colitis Questionnaire (WPAI:UC) v2.0 is an adaptation of the WPAI: Specific Health Profile is a measure of common patient reports of absence, expression, work productivity and activity impairment over the past 7 days (Reilly et al., Pharmacoeconomics, 4:353-365, 1993). The first question (Q1) asks whether the individual is currently employed (yes / no). If the individual answers "yes", they are asked to indicate the number of hours absent due to UC (Q2), the number of hours absent for other reasons (Q3), and the number of hours worked (Q4). If the answer to Q1 is yes and the answer to Q4 is >0, the individual is asked to indicate the impact of UC on work productivity on a numerical rating scale (NRS) from 0 to 10. Then, all individuals are asked to indicate the impact of UC on their daily activities on a 0 to 10 NRS (Q6). Four scores (absence, manifestation, work productivity, and activity impairment) are obtained from a scale and expressed as a percentage of impairment. A higher number indicates greater impairment and lower productivity (i.e., a worse outcome).

[0492] D.EuroQol 5-Dimensional 5-Level The EuroQol 5-Dimensional 5-Level (EQ-5D-5L) is a validated self-report health status questionnaire used to calculate health status utility scores for use in health economic analysis (EuroQol Group, Health Policy, 16:199-208, 1990; Brooks, Health Policy, 37:53-72, 1996; Herdman et al., Qual Life Res, 20:1727-1736, 2011; Janssen et al., Qual Life Res, 22:1717-1727, 2013). The EQ-5D-5L has two components: one is a health status profile consisting of five items that assess mobility, self-care, usual activity, pain / discomfort, and anxiety / depression; and the other is a visual analog scale (VAS) that measures health status. The EQ-5D-5L is designed to capture participants' current health status. The published weighting system allows for the creation of a single composite score for participants' health status. EQ 5D-5L is used in research to inform pharmacoeconomic assessments.

[0493] Example 6. Statistical analysis of the UC study This embodiment provides a summary of the statistical aspects of the GA45329 and GA45330 study designs, as well as a general approach to the analysis of endpoints supporting the study objectives.

[0494] The analysis of the GA45329 research data is fixed to the following milestones. Primary completion is defined as the date on which the last participant in the maintenance phase completes all primary endpoint assessments at week 52. Study completion is defined as the final visit date of the last participant across all phases of the study, including open-label extension (OLE). The analysis of the GA45330 research data is fixed to the following milestones: Primary completion is defined as the date on which the last participant in the induction treatment period completes all primary endpoint assessments at week 12. Study completion is defined as the final visit date of the end participant across all periods of the study, including OLE.

[0495] A. Statistical Hypothesis GA45329 research Under the common primary objective of the GA45329 study, it is hypothesized that afimkibart is superior to placebo in inducing and maintaining clinical remission. In the statistical trial, the relevant null and alternative hypotheses are formulated as follows: H0:p afimkibart -p プラセボ =0 versus H A :p afimkibart -p プラセボ ≠0, In the formula, p afimkibart -p プラセボ This represents the estimated effect of the treatment and is the difference in the percentage of patients who achieved clinical remission at a specific time point (week 12 or week 52) after being assigned to afimkibart versus placebo, as described in Example 1.

[0496] The GA45329 study will be considered positive if both the null hypotheses, based on clinical remission at week 12 and day 52, are rejected in favor of afimkibart. Each of these two-sided trials will be conducted at a 5% significance level. If the primary outcome is positive, the trial will proceed to a specified subset of key secondary endpoints (Example 1). All trials will be prioritized by family hierarchy and sequentially assessed by parallel gatekeeping via a truncated Hochberg multiple trial procedure with a truncation rate of 0.5. Such a multiple trial strategy ensures an overall type 1 error control of 5% (Dmitrienko et al., Biom J, 50:667-677, 2008).

[0497] Trials of secondary endpoints consider null and alternative hypotheses, similar to those defined for the joint primary endpoints described above. Inferences for primary and secondary endpoints are generally based on covariate-adjusted standardized estimators of marginal treatment effects, which are asymptotically normal and lead to Wald-type trials using point estimates and variance estimates (Rosenblum and van der Laan, Int J Biostat, 1(6), Article 13, 2010).

[0498] GA45330 research Under the primary objective of the GA45330 study, it is hypothesized that afimkibart is superior to placebo in inducing clinical remission. In the statistical trial, the relevant null and alternative hypotheses are formulated as follows: H0:p afimkibart -p プラセボ =0 versus H A :p afimkibart -p プラセボ ≠0, In the formula, p afimkibart -p プラセボ This represents the estimated effect of the treatment and is the difference in the percentage of patients who achieved clinical remission at 12 weeks after being assigned to afimkibart versus placebo, as described in Example 1.

[0499] The GA45330 study is considered positive if the above null hypothesis is rejected in favor of afimkibart.

[0500] This two-sided trial is conducted at a 5% significance level. If the primary outcome is positive, the trial proceeds to a specified subset of key secondary endpoints (Example 1). All trials are prioritized according to family hierarchy and sequentially rated by parallel gatekeeping via a truncation Hochberg multiple trial procedure with a truncation rate of 0.5. Such multiple trial strategies ensure an overall type 1 error control of 5% (Dmitrienko et al., Biom J, 50:667-677, 2008).

[0501] Trials of secondary endpoints consider null and alternative hypotheses, similar to those defined for the primary endpoints above. Inferences for primary and secondary endpoints are generally based on covariate-adjusted standardized estimators of marginal treatment effects, which are asymptotically normal and lead to Wald-type trials using point estimates and variance estimates (Rosenblum and van der Laan, Int J Biostat, 1(6), Article 13, 2010).

[0502] i. Determination of sample size GA45329 research In the GA45329 study, a total of approximately 400 participants were enrolled and randomly assigned to either afimkibart or placebo in a randomization ratio of 3:2. This resulted in approximately 240 participants being assigned to the afimkibart arm and 160 to the placebo arm. The limiting power to reject one of the null hypotheses in the primary analysis at a 5% significance level depends (partially) on the clinical remission rate under placebo treatment. In more recent Phase III UC trials, the placebo induction of clinical remission is estimated to be 10% (95% CI: 9%–13%), but this ratio depends on various factors, including the proportion of participants who had received prior advanced treatment (Sedano et al., J Crohns Colitis, 16:224-243, 2022).

[0503] The placebo rate of clinical remission in maintenance is further dependent on the design of the maintenance treatment period: randomized withdrawal or treat-through. Inputs of treat-through placebo rates from randomized withdrawal trials yield estimates ranging from 5%–6% and 12%–17% in patients with and without prior biological failure, respectively (Welty et al. 2020). Direct estimates under placebo-controlled treat-through trials enrolling both advanced treatment-naive and experienced participants are available from ULTRA2 (Sandborn et al., Gastroenterology, 142:257-265.e3, 2012, primary analysis set excluding participants from unsuitable sites) and more recently from ELEVATE UC52 (Sandborn et al., The Lancet, 401:1159-1171, 2023, primary analysis set excluding participants with baseline mMS < 5). The clinical remission rates observed at week 52 in the placebo arm of these studies were 9% (95% CI: 6%–13%) and 7% (95% CI: 4%–12%), respectively.

[0504] The safety objective further requires a placebo arm large enough to ensure that there are placebo-treated participants throughout the 52-week treatment period. In ULTRA2 and ELEVATE UC52, 56 / 246 (23%) and at least 39 / 135 (29%) of placebo-treated patients completed the 52-week treatment, respectively. Rather than directly assuming a placebo completion rate, the expected number of placebo completers, both overall and among completers, can be estimated from the assumed maintenance clinical remission rate in the placebo arm. In ULTRA2 and ELEVATE UC52, the clinical remission rates at week 52 among completers in the placebo arm were 38% and 23%, respectively.

[0505] Within the range of these ratio values, Table 18 shows the key operational characteristics of the proposed sample sizes. Throughout, the treatment effect remained fixed at 15%, which is considered clinically meaningful and achievable given the Phase 2 efficacy findings for afimkibart in UC. [Table 18]

[0506] Table 18 considers the limiting forces for detecting a given treatment effect on either of the joint primary endpoints. The corresponding combined force (for both joint primary endpoints) is at least 0.94. 2 = 88%

[0507] GA45330 research In the GA45330 study, a total of approximately 350 participants were enrolled and randomly assigned to either afimkibart or placebo in a randomization ratio of 3:2. This resulted in approximately 210 participants being assigned to the afimkibart arm and 140 to the placebo arm. The power to reject the null hypothesis in the primary analysis at a 5% significance level (partially) depends on the clinical remission rate under placebo treatment. In more recent Phase III UC trials, the placebo induction of clinical remission is estimated to be 10% (95% CI: 9%–13%), but this ratio depends on various factors, including the proportion of participants who had received prior advanced treatment (Sedano et al., J Crohns Colitis, 16:224-243, 2022).

[0508] Table 19 shows the power of the proposed sample sizes within the range of placebo rates. Throughout, the treatment effect was fixed at 15%, which is considered clinically meaningful and achievable given the Phase II efficacy findings for afimkibart in UC. [Table 19]

[0509] B. Analysis Set In both studies, each planned analysis incorporates data from a specific set of participants. These participant analysis sets are broadly defined in Table 20. Generally, relevant data for a given participa...

Claims

1. A method for treating inflammatory bowel disease (IBD) in a patient, the method comprising administering an effective amount of anti-TNF-like ligand 1A (TL1A) antibody to the patient in a drug regimen including an induction phase, the induction phase comprising only four administrations of the anti-TL1A antibody. (i) The second dose of the anti-TL1A antibody is administered approximately two weeks after the first dose; (ii) The third dose of the anti-TL1A antibody is administered approximately four weeks after the second dose; and (iii) The fourth dose of the anti-TL1A antibody is administered approximately four weeks after the third dose. The aforementioned anti-TL1A antibody has the following complementarity-determining region (CDR): (a) CDR-H1 containing the amino acid sequence of SEQ ID NO: 3; (b) CDR-H2 containing the amino acid sequence of SEQ ID NO: 4; (c) CDR-H3 containing the amino acid sequence of SEQ ID NO: 5; (d) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6; (e) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7; and (f) A method comprising CDR-L3 containing the amino acid sequence of SEQ ID NO:

8.

2. A method for treating IBD in a patient, the method comprising administering an effective amount of anti-TL1A antibody to the patient in a drug regimen including an induction phase and a maintenance phase, (a) The induction period includes only four administrations of the anti-TL1A antibody, (i) The second dose of the anti-TL1A antibody is administered approximately two weeks after the first dose; (ii) The third dose of the anti-TL1A antibody is administered approximately four weeks after the second dose; and (iii) The fourth dose of the anti-TL1A antibody is administered approximately four weeks after the third dose; and (b) The maintenance period comprises administering the anti-TL1A antibody every four weeks, The aforementioned anti-TL1A antibody has the following CDR: (a) CDR-H1 containing the amino acid sequence of SEQ ID NO: 3; (b) CDR-H2 containing the amino acid sequence of SEQ ID NO: 4; (c) CDR-H3 containing the amino acid sequence of SEQ ID NO: 5; (d) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6; (e) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7; and (f) A method comprising CDR-L3 containing the amino acid sequence of SEQ ID NO:

8.

3. The method according to claim 1 or 2, wherein during the induction period, the anti-TL1A antibody is administered intravenously at a dose of approximately 500 mg.

4. The method according to claim 1 or 2, wherein during the induction period, the anti-TL1A antibody is administered subcutaneously at a dose of approximately 500 mg.

5. The method according to any one of claims 1 to 4, wherein the induction period has a duration of approximately 12 weeks.

6. (a) The first administration of the anti-TL1A antibody is performed around the first day of week 0; (b) The second administration of the anti-TL1A antibody is performed around the first day of the second week; (c) The third administration of the anti-TL1A antibody is performed around the first day of the sixth week; and (d) The method according to claim 5, wherein the fourth administration of the anti-TL1A antibody is performed around the first day of the tenth week.

7. The method according to any one of claims 1 and 3 to 6, wherein the drug regimen further comprises a maintenance phase.

8. The method according to any one of claims 2 to 7, wherein during the maintenance period, the anti-TL1A antibody is administered subcutaneously at a dose of approximately 150 mg.

9. The method according to any one of claims 2 to 7, wherein during the maintenance period, the anti-TL1A antibody is administered subcutaneously at a dose of approximately 450 mg.

10. The method according to any one of claims 2 to 9, wherein the maintenance period comprises at least two administrations of the anti-TL1A antibody.

11. The method according to claim 10, wherein the maintenance period includes subcutaneous administration of the anti-TL1A antibody every four weeks.

12. The method according to claim 10 or 11, wherein the maintenance period includes subcutaneous administration of the anti-TL1A antibody every two weeks.

13. The method according to any one of claims 10 to 12, wherein the maintenance period comprises (i) at least one interval in which the anti-TL1A antibody is administered every four weeks and (ii) at least one interval in which the anti-TL1A antibody is administered every two weeks.

14. The method according to any one of claims 2 to 13, wherein the maintenance period comprises 11 administrations of the anti-TL1A antibody.

15. The method according to any one of claims 2 to 14, wherein the maintenance period has a duration of approximately 40 weeks.

16. The method according to any one of claims 2 to 15, wherein a corticosteroid is administered to the patient daily during the induction phase, and the dose of the corticosteroid is gradually reduced during the maintenance phase.

17. The method according to claim 16, wherein the administration of the corticosteroid is discontinued during the maintenance phase.

18. The method according to claim 16 or 17, wherein the corticosteroid is prednisone or an equivalent thereof, budesonide, or budesonide multimatrix (MMX).

19. The corticosteroid is prednisone or its equivalent, and is administered orally to the patient at a dose exceeding 10 mg per day during the induction phase, and then gradually tapered. (i) gradually reduce the dose by 5 mg per week until the patient receives a dose of 10 mg per day; and (ii) The method according to claim 18, comprising gradually reducing the dose by 2.5 mg per week until the dose reaches 0 mg per week.

20. The method according to claim 18, wherein the corticosteroid is prednisone or an equivalent thereof, and is administered orally to the patient at a dose of 10 mg or less per day during the induction phase, and the tapering comprises gradually reducing the dose by 2.5 mg per week until the dose reaches 0 mg per week.

21. (I) The corticosteroid is budesonide or budesonide MMX, and is administered orally to the patient at a dose of 9 mg or less per day during the induction period, and the dose is gradually reduced. (i) Administer the corticosteroid at a dose of 9 mg every other day for two weeks; (ii) administering the corticosteroid at a dose of 9 mg every three days for two weeks; and (iii) discontinuing the administration of the corticosteroid; or (II) The corticosteroid is budesonide, and during the induction phase, it is administered orally to the patient at a dose of 6 mg or less per day, and the dose is gradually reduced. (i) Reduce the dose to 3 mg per day over a period of two weeks, and then, (ii) The method according to claim 18, comprising discontinuing administration of budesonide.

22. The method according to any one of claims 2 to 21, wherein the first dose during the maintenance phase is administered approximately two weeks after the fourth dose during the induction phase.

23. The method according to any one of claims 2 to 22, wherein the drug regimen has a duration of approximately 52 weeks.

24. (a) The first dose during the induction period is administered around the first day of week 0; (b) The second dose during the induction period is administered around the first day of the second week; (c) The third dose during the induction period is administered around the first day of the sixth week; (d) The fourth dose during the induction period is administered around the first day of the tenth week; (e) The first dose of the maintenance period is administered around the first day of the 12th week; and (f) The method according to claim 23, wherein subsequent administrations during the maintenance period are performed around the first day of weeks 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52.

25. The method according to any one of claims 1 to 24, wherein the drug regimen further comprises an extension period including the administration of one or more additional drug cycles of the anti-TL1A antibody.

26. (a) Whether the extension period includes subcutaneous administration of the anti-TL1A antibody every four weeks; (b) The extension period includes subcutaneous administration of the anti-TL1A antibody every two weeks; or (c) The method of claim 25, wherein the extension period includes (i) at least one interval in which the anti-TL1A antibody is administered every four weeks and (ii) at least one interval in which the anti-TL1A antibody is administered every two weeks.

27. The method according to claim 25 or 26, wherein the one or more drug administration cycles during the extension period are administered to the patient after the disease worsens during the maintenance period.

28. The method according to any one of claims 1 to 27, wherein the IBD is ulcerative colitis (UC).

29. The method according to claim 28, wherein the UC is moderate to severe active ulcerative colitis.

30. The method according to claim 28 or 29, wherein the patient has a modified Mayo score (mMS) between 5 and 9 points.

31. The method according to any one of claims 28 to 30, wherein the patient has a Mayo endoscopic score (ES) of 2 or 3.

32. The method according to any one of claims 1 to 27, wherein the IBD is Crohn's disease (CD).

33. The method according to claim 32, wherein the CD is moderate to severely active.

34. (a) The patient has a simplified Crohn's disease endoscopic score of 6 or higher (SES-CD); or (b) The method according to claim 32 or 33, wherein the patient has only isolated ileal disease and has four or more SES-CDs.

35. The method according to any one of claims 32 to 34, wherein the patient has a Crohn's disease activity index (CDAI) of at least 220 and 450 or less.

36. The method according to any one of claims 28 to 35, wherein the patient has been previously treated with treatment for UC or CD and has experienced an inadequate response to the treatment, loss of response to the treatment, and / or intolerance to the treatment.

37. The method according to claim 36, wherein the treatment is a conventional treatment.

38. The method according to claim 37, wherein the conventional treatment comprises the administration of a steroid, an immunomodulator, or an oral aminosalicylate.

39. The method according to claim 36, wherein the treatment was an advanced treatment.

40. The method according to claim 39, wherein the advanced treatment comprises the administration of an antitumor necrosis factor (TNF) agent, an antiintegrin agent, an anti-IL12 / IL23 agent, a Janus kinase (JAK) inhibitor, or a sphingosine-1-phosphate (S1P) inhibitor.

41. A method for treating ulcerative colitis (UC) in a patient, the method comprising administering to the patient an effective amount of anti-TNF-like ligand 1A (TL1A) antibody in a drug regimen including an induction phase and a maintenance phase, (a) The induction period comprises only four intravenous administrations of the anti-TL1A antibody in doses of approximately 500 mg each. (i) The second dose of the anti-TL1A antibody is administered approximately two weeks after the first dose; (ii) The third dose of the anti-TL1A antibody is administered approximately four weeks after the second dose; and (iii) The fourth dose of the anti-TL1A antibody is administered approximately four weeks after the third dose; and (b) The maintenance period includes subcutaneous administration of the anti-TL1A antibody at a dose of approximately 450 mg every four weeks. The aforementioned anti-TL1A antibody has the following CDR: (a) CDR-H1 containing the amino acid sequence of SEQ ID NO: 3; (b) CDR-H2 containing the amino acid sequence of SEQ ID NO: 4; (c) CDR-H3 containing the amino acid sequence of SEQ ID NO: 5; (d) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6; (e) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7; and (f) A method comprising CDR-L3 containing the amino acid sequence of SEQ ID NO:

8.

42. The method according to any one of claims 1 to 31 and 36 to 41, wherein in a patient population treated according to the method, the treatment results in an increase in the proportion of patients who achieve clinical remission at the end of the induction period compared to a reference population.

43. The method according to claim 42, wherein the induction period has a duration of approximately 12 weeks, and the treatment results in an increase in the percentage of patients who achieve clinical remission at 12 weeks.

44. The method according to any one of claims 1 to 31 and 36 to 41, wherein in a patient population treated according to the method, the treatment results in an increase in the proportion of patients who achieve clinical remission at the end of the maintenance period compared to a reference population.

45. The method according to claim 44, wherein the drug regimen has a duration of approximately 52 weeks, and the treatment results in an increased percentage of patients achieving clinical remission at 52 weeks.

46. The method according to any one of claims 42 to 45, wherein clinical remission is a modified Mayo score (mMS) ≤ 2, with a bowel movement frequency subscore (SFS) = 0 or 1, a rectal bleeding subscore (RBS) = 0, and an endoscopy subscore (ES) = 0 or 1.

47. A method for treating Crohn's disease (CD) in a patient, the method comprising administering an effective amount of anti-TNF-like ligand 1A (TL1A) antibody to the patient in a drug regimen including an induction phase and a maintenance phase, (a) The induction period comprises only four intravenous administrations of the anti-TL1A antibody in doses of approximately 500 mg each. (i) The second dose of the anti-TL1A antibody is administered approximately two weeks after the first dose; (ii) The third dose of the anti-TL1A antibody is administered approximately four weeks after the second dose; and (iii) The fourth dose of the anti-TL1A antibody is administered approximately four weeks after the third dose; and (b) The maintenance period includes subcutaneous administration of the anti-TL1A antibody at a dose of approximately 450 mg every four weeks. The aforementioned anti-TL1A antibody has the following CDR: (a) CDR-H1 containing the amino acid sequence of SEQ ID NO: 3; (b) CDR-H2 containing the amino acid sequence of SEQ ID NO: 4; (c) CDR-H3 containing the amino acid sequence of SEQ ID NO: 5; (d) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6; (e) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7; and (f) A method comprising CDR-L3 containing the amino acid sequence of SEQ ID NO:

8.

48. A method for treating Crohn's disease (CD) in a patient, the method comprising administering an effective amount of anti-TNF-like ligand 1A (TL1A) antibody to the patient in a drug regimen including an induction phase and a maintenance phase, (a) The induction period comprises only four intravenous administrations of the anti-TL1A antibody in doses of approximately 500 mg each. (i) The second dose of the anti-TL1A antibody is administered approximately two weeks after the first dose; (ii) The third dose of the anti-TL1A antibody is administered approximately four weeks after the second dose; and (iii) The fourth dose of the anti-TL1A antibody is administered approximately four weeks after the third dose; and (b) The maintenance period includes subcutaneous administration of the anti-TL1A antibody at a dose of approximately 150 mg every four weeks. The aforementioned anti-TL1A antibody has the following CDR: (a) CDR-H1 containing the amino acid sequence of SEQ ID NO: 3; (b) CDR-H2 containing the amino acid sequence of SEQ ID NO: 4; (c) CDR-H3 containing the amino acid sequence of SEQ ID NO: 5; (d) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6; (e) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7; and (f) A method comprising CDR-L3 containing the amino acid sequence of SEQ ID NO:

8.

49. The method according to any one of claims 1 to 27, 32 to 40, 47, and 48, wherein in a patient population treated according to the method, the treatment results in an increase in the proportion of patients who achieve clinical remission at the end of the induction period compared to a reference population.

50. The method according to claim 49, wherein the induction period has a duration of approximately 12 weeks, and the treatment results in an increase in the percentage of patients who achieve clinical remission at 12 weeks.

51. The method according to any one of claims 1 to 27, 32 to 40, and 47 to 50, wherein in a patient population treated according to the method, the treatment results in an increase in the proportion of patients who achieve clinical remission at the end of the maintenance period compared to a reference population.

52. The method according to claim 51, wherein the drug regimen has a duration of approximately 52 weeks, and the treatment results in an increased percentage of patients achieving clinical remission at 52 weeks.

53. The method according to any one of claims 49 to 52, wherein clinical remission is defined as a Crohn's disease activity index (CDAI) of less than 150.

54. The method according to any one of claims 1 to 27, 32 to 40, and 47 to 53, wherein in a patient population treated according to the method, the treatment results in an increase in the proportion of patients who achieve an endoscopic response at the end of the induction period compared to a reference population.

55. The method according to claim 54, wherein the induction period has a duration of approximately 12 weeks, and the procedure results in an increase in the percentage of patients who achieve an endoscopic response at 12 weeks.

56. The method according to any one of claims 1 to 27, 32 to 40, and 47 to 55, wherein in a patient population treated according to the method, the treatment results in an increase in the proportion of patients who achieved an endoscopic response at the end of the maintenance phase compared to a reference population.

57. The method according to claim 56, wherein the drug regimen has a duration of approximately 52 weeks, and the treatment results in an increased percentage of patients achieving an endoscopic response at 52 weeks.

58. The method according to any one of claims 54 to 57, wherein the endoscopic response is a simplified Crohn's disease endoscopic score (SES-CD) that is at least 50% lower than the baseline SES-CD.

59. The method according to any one of claims 42 to 46 and 49 to 58, wherein the reference population is a population of patients who have never been treated with an anti-TL1A antibody.

60. The method according to claim 59, wherein the reference population is a population of patients treated with a placebo.

61. The method according to any one of claims 1 to 60, wherein the patient is determined to be a non-carrier of haplotype B of TNFSF15.

62. The aforementioned anti-TL1A antibody (a) A heavy chain variable (VH) domain comprising an amino acid sequence having at least 95% sequence identity with the amino acid sequence of SEQ ID NO: 1; and / or (b) The method according to any one of claims 1 to 61, comprising a light chain variable (VL) domain having an amino acid sequence having at least 95% sequence identity with the amino acid sequence of SEQ ID NO:

2.

63. The aforementioned anti-TL1A antibody (a) A VH domain containing the amino acid sequence of Sequence ID No. 1; and / or (b) The method according to claim 62, comprising a VL domain containing the amino acid sequence of SEQ ID NO:

2.

64. The aforementioned anti-TL1A antibody (a) VH domain containing the amino acid sequence of SEQ ID NO: 1; and (b) The method according to claim 63, comprising a VL domain containing the amino acid sequence of SEQ ID NO:

2.

65. The aforementioned anti-TL1A antibody (a) a heavy chain comprising an amino acid sequence having at least 95% sequence identity with the amino acid sequence of SEQ ID NO: 9 or SEQ ID NO: 11; and / or (b) The method according to any one of claims 1 to 64, comprising a light chain having an amino acid sequence having at least 95% sequence identity with the amino acid sequence of SEQ ID NO:

10.

66. The aforementioned anti-TL1A antibody (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 9; and / or (b) The method according to claim 65, comprising a light chain having the amino acid sequence of SEQ ID NO:

10.

67. The aforementioned anti-TL1A antibody (a) a heavy chain containing the amino acid sequence of SEQ ID NO: 9; and (b) The method according to claim 66, comprising a light chain having the amino acid sequence of SEQ ID NO:

10.

68. The method according to any one of claims 1 to 67, wherein the anti-TL1A antibody is afimkibart.

69. A method for treating inflammatory bowel disease (IBD) in a patient, the method comprising administering an effective amount of anti-TNF-like ligand 1A (TL1A) antibody to the patient in a drug regimen including an induction phase, the induction phase comprising only four administrations of the anti-TL1A antibody. (i) The second dose of the anti-TL1A antibody is administered approximately two weeks after the first dose; (ii) The third dose of the anti-TL1A antibody is administered approximately four weeks after the second dose; and (iii) The fourth dose of the anti-TL1A antibody is administered approximately four weeks after the third dose; The aforementioned anti-TL1A antibody is (a) a heavy chain having at least 95% sequence identity with SEQ ID NO: 9, or containing an amino acid sequence having the amino acid sequence of SEQ ID NO: 9; and (b) A method comprising a light chain having at least 95% sequence identity with SEQ ID NO: 10, or an amino acid sequence having the amino acid sequence of SEQ ID NO:

10.

70. The method according to claim 69, wherein the IBD is UC.

71. The method according to claim 69, wherein the IBD is a CD.

72. A method for treating IBD in a patient, the method comprising administering an effective amount of anti-TL1A antibody to the patient in a drug regimen including an induction phase and a maintenance phase, (a) The induction period includes only four administrations of the anti-TL1A antibody, (i) The second dose of the anti-TL1A antibody is administered approximately two weeks after the first dose; (ii) The third dose of the anti-TL1A antibody is administered approximately four weeks after the second dose; and (iii) The fourth dose of the anti-TL1A antibody is administered approximately four weeks after the third dose; and (b) The maintenance period comprises administering the anti-TL1A antibody every four weeks; The aforementioned anti-TL1A antibody is (a) a heavy chain having at least 95% sequence identity with SEQ ID NO: 9, or containing an amino acid sequence having the amino acid sequence of SEQ ID NO: 9; and (b) A method comprising a light chain having at least 95% sequence identity with SEQ ID NO: 10, or an amino acid sequence having the amino acid sequence of SEQ ID NO:

10.

73. The method according to claim 72, wherein the IBD is UC.

74. The method according to claim 72, wherein the IBD is a CD.

75. The method according to any one of claims 1 to 74, wherein the anti-TL1A antibody is administered in combination with one or more additional therapeutic agents.

76. The method according to any one of claims 1 to 75, wherein the patient is a human being.

77. A kit comprising an anti-TNF-like ligand 1A (TL1A) antibody and a package insert containing instructions for using the antibody to treat inflammatory bowel disease (IBD) in patients requiring treatment of IBD according to any one of claims 1 to 76.

78. An anti-TL1A antibody for use in the treatment of IBD in a patient, wherein an effective amount of the anti-TL1A antibody is administered to the patient in a drug regimen including an induction phase, and the induction phase includes only four administrations of the anti-TL1A antibody. (i) The second dose of the anti-TL1A antibody will be administered approximately two weeks after the first dose; (ii) The third dose of the anti-TL1A antibody will be administered approximately four weeks after the second dose; and (iii) The fourth dose of the anti-TL1A antibody will be administered approximately four weeks after the third dose, and The aforementioned anti-TL1A antibody has the following complementarity-determining region (CDR): (a) CDR-H1 containing the amino acid sequence of SEQ ID NO: 3; (b) CDR-H2 containing the amino acid sequence of SEQ ID NO: 4; (c) CDR-H3 containing the amino acid sequence of SEQ ID NO: 5; (d) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6; (e) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7; and (f) An anti-TL1A antibody containing CDR-L3, which has the amino acid sequence of SEQ ID NO:

8.

79. An anti-TL1A antibody for use in the treatment of IBD in a patient, wherein an effective amount of the anti-TL1A antibody is administered to the patient in a drug regimen including an induction phase and a maintenance phase. (a) The induction period includes only four administrations of the anti-TL1A antibody, (i) The second administration of the anti-TL1A antibody will be performed approximately two weeks after the first administration; (ii) The third dose of the anti-TL1A antibody will be administered approximately four weeks after the second dose; and (iii) The fourth dose of the anti-TL1A antibody will be administered approximately four weeks after the third dose; and (b) The maintenance period comprises administering the anti-TL1A antibody every four weeks, and The aforementioned anti-TL1A antibody has the following CDR: (a) CDR-H1 containing the amino acid sequence of SEQ ID NO: 3; (b) CDR-H2 containing the amino acid sequence of SEQ ID NO: 4; (c) CDR-H3 containing the amino acid sequence of SEQ ID NO: 5; (d) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6; (e) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7; and (f) An anti-TL1A antibody containing CDR-L3, which has the amino acid sequence of SEQ ID NO:

8.

80. An anti-TL1A antibody for use in the treatment of ulcerative colitis in a patient, wherein an effective amount of the anti-TL1A antibody is administered to the patient in a drug regimen that includes induction and maintenance phases. (a) The induction period comprises only four intravenous administrations of the anti-TL1A antibody in doses of approximately 500 mg each. (i) The second dose of the anti-TL1A antibody will be administered approximately two weeks after the first dose; (ii) The third dose of the anti-TL1A antibody will be administered approximately four weeks after the second dose; and (iii) The fourth dose of the anti-TL1A antibody will be administered approximately four weeks after the third dose; and (b) The maintenance period comprises subcutaneous administration of the anti-TL1A antibody at a dose of approximately 450 mg every four weeks, and The aforementioned anti-TL1A antibody has the following CDR: (a) CDR-H1 containing the amino acid sequence of SEQ ID NO: 3; (b) CDR-H2 containing the amino acid sequence of SEQ ID NO: 4; (c) CDR-H3 containing the amino acid sequence of SEQ ID NO: 5; (d) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6; (e) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7; and (f) An anti-TL1A antibody containing CDR-L3, which has the amino acid sequence of SEQ ID NO:

8.

81. An anti-TL1A antibody for use in the treatment of a patient with CD, wherein an effective amount of the anti-TL1A antibody is administered to the patient in a drug regimen that includes induction and maintenance phases. (a) The induction period comprises only four intravenous administrations of the anti-TL1A antibody in doses of approximately 500 mg each. (i) The second dose of the anti-TL1A antibody will be administered approximately two weeks after the first dose; (ii) The third dose of the anti-TL1A antibody will be administered approximately four weeks after the second dose; and (iii) The fourth dose of the anti-TL1A antibody will be administered approximately four weeks after the third dose; and (b) The maintenance period comprises subcutaneous administration of the anti-TL1A antibody at a dose of approximately 450 mg every four weeks, and The aforementioned anti-TL1A antibody has the following CDR: (a) CDR-H1 containing the amino acid sequence of SEQ ID NO: 3; (b) CDR-H2 containing the amino acid sequence of SEQ ID NO: 4; (c) CDR-H3 containing the amino acid sequence of SEQ ID NO: 5; (d) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6; (e) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7; and (f) An anti-TL1A antibody containing CDR-L3, which has the amino acid sequence of SEQ ID NO:

8.

82. An anti-TL1A antibody for use in the treatment of a patient with CD, wherein an effective amount of the anti-TL1A antibody is administered to the patient in a drug regimen that includes induction and maintenance phases. (a) The induction period comprises only four intravenous administrations of the anti-TL1A antibody in doses of approximately 500 mg each. (i) The second dose of the anti-TL1A antibody will be administered approximately two weeks after the first dose; (ii) The third dose of the anti-TL1A antibody will be administered approximately four weeks after the second dose; and (iii) The fourth dose of the anti-TL1A antibody will be administered approximately four weeks after the third dose; and (b) The maintenance period comprises subcutaneous administration of the anti-TL1A antibody at a dose of approximately 150 mg every four weeks, and The aforementioned anti-TL1A antibody has the following CDR: (a) CDR-H1 containing the amino acid sequence of SEQ ID NO: 3; (b) CDR-H2 containing the amino acid sequence of SEQ ID NO: 4; (c) CDR-H3 containing the amino acid sequence of SEQ ID NO: 5; (d) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6; (e) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7; and (f) An anti-TL1A antibody containing CDR-L3, which has the amino acid sequence of SEQ ID NO:

8.

83. An anti-TL1A antibody for use in the treatment of IBD in a patient, wherein an effective amount of the anti-TL1A antibody is administered to the patient in a drug regimen that includes an induction phase, and the induction phase includes only four administrations of the anti-TL1A antibody. (i) The second dose of the anti-TL1A antibody will be administered approximately two weeks after the first dose; (ii) The third dose of the anti-TL1A antibody will be administered approximately four weeks after the second dose; and (iii) The fourth dose of the anti-TL1A antibody will be administered approximately four weeks after the third dose, and The aforementioned anti-TL1A antibody is (a) a heavy chain having at least 95% sequence identity with SEQ ID NO: 9, or containing an amino acid sequence having the amino acid sequence of SEQ ID NO: 9; and (b) An anti-TL1A antibody comprising a light chain having at least 95% sequence identity with SEQ ID NO: 10, or an amino acid sequence having the amino acid sequence of SEQ ID NO:

10.

84. An anti-TL1A antibody for use in the treatment of IBD in patients, wherein an effective amount of the anti-TL1A antibody is administered to the patient in a drug regimen including induction and maintenance phases. (a) The induction period includes only four administrations of the anti-TL1A antibody, (i) The second dose of the anti-TL1A antibody will be administered approximately two weeks after the first dose; (ii) The third dose of the anti-TL1A antibody will be administered approximately four weeks after the second dose; and (iii) The fourth dose of the anti-TL1A antibody will be administered approximately four weeks after the third dose; and (b) The maintenance period comprises administering the anti-TL1A antibody every four weeks, and The aforementioned anti-TL1A antibody is (a) a heavy chain having at least 95% sequence identity with SEQ ID NO: 9, or containing an amino acid sequence having the amino acid sequence of SEQ ID NO: 9; and (b) An anti-TL1A antibody comprising a light chain having at least 95% sequence identity with SEQ ID NO: 10, or an amino acid sequence having the amino acid sequence of SEQ ID NO:

10.

85. The use of an anti-TL1A antibody in the manufacture of a pharmaceutical product for treating IBD in a patient, wherein an effective amount of the anti-TL1A antibody is administered to the patient in a drug regimen including an induction period, the induction period comprising only four administrations of the anti-TL1A antibody. (i) The second dose of the anti-TL1A antibody will be administered approximately two weeks after the first dose; (ii) The third dose of the anti-TL1A antibody will be administered approximately four weeks after the second dose; and (iii) The fourth dose of the anti-TL1A antibody will be administered approximately four weeks after the third dose, and The aforementioned anti-TL1A antibody has the following complementarity-determining region (CDR): (a) CDR-H1 containing the amino acid sequence of SEQ ID NO: 3; (b) CDR-H2 containing the amino acid sequence of SEQ ID NO: 4; (c) CDR-H3 containing the amino acid sequence of SEQ ID NO: 5; (d) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6; (e) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7; and (f) Use of CDR-L3 containing the amino acid sequence of SEQ ID NO:

8.

86. The use of an anti-TL1A antibody in the manufacture of a pharmaceutical product for treating IBD in a patient, wherein an effective amount of the anti-TL1A antibody is administered to the patient in a drug regimen including an induction phase and a maintenance phase. (a) The induction period includes only four administrations of the anti-TL1A antibody, (i) The second dose of the anti-TL1A antibody will be administered approximately two weeks after the first dose; (ii) The third dose of the anti-TL1A antibody will be administered approximately four weeks after the second dose; and (iii) The fourth dose of the anti-TL1A antibody will be administered approximately four weeks after the third dose; and (b) The maintenance period comprises administering the anti-TL1A antibody every four weeks, and The aforementioned anti-TL1A antibody has the following CDR: (a) CDR-H1 containing the amino acid sequence of SEQ ID NO: 3; (b) CDR-H2 containing the amino acid sequence of SEQ ID NO: 4; (c) CDR-H3 containing the amino acid sequence of SEQ ID NO: 5; (d) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6; (e) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7; and (f) Use of CDR-L3 containing the amino acid sequence of SEQ ID NO:

8.

87. The use of an anti-TL1A antibody in the manufacture of a pharmaceutical product for treating ulcerative colitis in a patient, wherein an effective amount of the anti-TL1A antibody is administered to the patient in a drug regimen that includes an induction phase and a maintenance phase. (a) The induction period comprises only four intravenous administrations of the anti-TL1A antibody in doses of approximately 500 mg each. (i) The second dose of the anti-TL1A antibody will be administered approximately two weeks after the first dose; (ii) The third dose of the anti-TL1A antibody will be administered approximately four weeks after the second dose; and (iii) The fourth dose of the anti-TL1A antibody will be administered approximately four weeks after the third dose; and (b) The maintenance period comprises subcutaneous administration of the anti-TL1A antibody at a dose of approximately 450 mg every four weeks, and The aforementioned anti-TL1A antibody has the following CDR: (a) CDR-H1 containing the amino acid sequence of SEQ ID NO: 3; (b) CDR-H2 containing the amino acid sequence of SEQ ID NO: 4; (c) CDR-H3 containing the amino acid sequence of SEQ ID NO: 5; (d) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6; (e) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7; and (f) Use of CDR-L3 containing the amino acid sequence of SEQ ID NO:

8.

88. The use of anti-TL1A antibodies in the manufacture of pharmaceuticals for treating a patient's CD, wherein an effective amount of anti-TL1A antibodies is administered to the patient in a drug regimen including induction and maintenance phases. (a) The induction period comprises only four intravenous administrations of the anti-TL1A antibody in doses of approximately 500 mg each. (i) The second dose of the anti-TL1A antibody will be administered approximately two weeks after the first dose; (ii) The third dose of the anti-TL1A antibody will be administered approximately four weeks after the second dose; and (iii) The fourth dose of the anti-TL1A antibody will be administered approximately four weeks after the third dose; and (b) The maintenance period comprises subcutaneous administration of the anti-TL1A antibody at a dose of approximately 450 mg every four weeks, and The aforementioned anti-TL1A antibody has the following CDR: (a) CDR-H1 containing the amino acid sequence of SEQ ID NO: 3; (b) CDR-H2 containing the amino acid sequence of SEQ ID NO: 4; (c) CDR-H3 containing the amino acid sequence of SEQ ID NO: 5; (d) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6; (e) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7; and (f) Use of CDR-L3 containing the amino acid sequence of SEQ ID NO:

8.

89. The use of anti-TL1A antibodies in the manufacture of pharmaceuticals for treating a patient's CD, wherein an effective amount of anti-TL1A antibodies is administered to the patient in a drug regimen including induction and maintenance phases. (a) The induction period comprises only four intravenous administrations of the anti-TL1A antibody in doses of approximately 500 mg each. (i) The second dose of the anti-TL1A antibody will be administered approximately two weeks after the first dose; (ii) The third dose of the anti-TL1A antibody will be administered approximately four weeks after the second dose; and (iii) The fourth dose of the anti-TL1A antibody will be administered approximately four weeks after the third dose; and (b) The maintenance period comprises subcutaneous administration of the anti-TL1A antibody at a dose of approximately 150 mg every four weeks, and The aforementioned anti-TL1A antibody has the following CDR: (a) CDR-H1 containing the amino acid sequence of SEQ ID NO: 3; (b) CDR-H2 containing the amino acid sequence of SEQ ID NO: 4; (c) CDR-H3 containing the amino acid sequence of SEQ ID NO: 5; (d) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6; (e) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7; and (f) Use of CDR-L3 containing the amino acid sequence of SEQ ID NO:

8.

90. The use of an anti-TL1A antibody in the manufacture of a pharmaceutical product for treating IBD in a patient, wherein an effective amount of the anti-TL1A antibody is administered to the patient in a drug regimen that includes an induction period, and the induction period comprises only four administrations of the anti-TL1A antibody. (i) The second dose of the anti-TL1A antibody will be administered approximately two weeks after the first dose; (ii) The third dose of the anti-TL1A antibody will be administered approximately four weeks after the second dose; and (iii) The fourth dose of the anti-TL1A antibody will be administered approximately four weeks after the third dose, and The aforementioned anti-TL1A antibody is (a) a heavy chain having at least 95% sequence identity with SEQ ID NO: 9, or containing an amino acid sequence having the amino acid sequence of SEQ ID NO: 9; and (b) Use comprising a light chain having at least 95% sequence identity with SEQ ID NO: 10, or an amino acid sequence having the amino acid sequence of SEQ ID NO:

10.

91. The use of anti-TL1A antibodies in the manufacture of pharmaceuticals for treating IBD in patients, wherein an effective amount of anti-TL1A antibodies is administered to the patient in a drug regimen including induction and maintenance phases. (a) The induction period includes only four administrations of the anti-TL1A antibody, (i) The second dose of the anti-TL1A antibody will be administered approximately two weeks after the first dose; (ii) The third dose of the anti-TL1A antibody will be administered approximately four weeks after the second dose; and (iii) The fourth dose of the anti-TL1A antibody will be administered approximately four weeks after the third dose; and (b) The maintenance period comprises administering the anti-TL1A antibody every four weeks, and The aforementioned anti-TL1A antibody is (a) a heavy chain having at least 95% sequence identity with SEQ ID NO: 9, or containing an amino acid sequence having the amino acid sequence of SEQ ID NO: 9; and (b) Use comprising a light chain having at least 95% sequence identity with SEQ ID NO: 10, or an amino acid sequence having the amino acid sequence of SEQ ID NO: 10.

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