Methods for treatment of pediatric inflammatory bowel disease with an Anti-TL1a antibody

Abstract

The present disclosure provides methods and compositions for treating inflammatory bowel disease (IBD), e.g., ulcerative colitis (UO) or Crohn's disease (CD), with a therapeutic dose of an anti- TNF-like ligand 1 A (TL1 A) agent (e.g., anti-TL1 A antibody) in pediatric patients.

Description

[0001] PATENT

[0002] Attorney Docket No: 50474-373WO3

[0003] Genentech Docket No: P39855-WO-1

[0004] METHODS FOR TREATMENT OF PEDIATRIC INFLAMMATORY BOWEL DISEASE WITH AN ANTI-TL1A ANTIBODY

[0005] SEQUENCE LISTING

[0006] The instant application contains a Sequence Listing which has been submitted electronically in XML format and is hereby incorporated by reference in its entirety. Said XML copy, created on January 29, 2026, is named 50474-373WO3_Sequence_Listing_1_29_26 and is 110,420 bytes in size.

[0007] TECHNICAL FIELD

[0008] The present invention relates to the treatment of signs and symptoms of inflammatory bowel disease (IBD), e.g., ulcerative colitis (UC) or Crohn’s disease (CD), with an anti-tumor necrosis factor-like ligand 1A (TL1A) agent (e.g., anti-TL1 A antibody) in pediatric patients.

[0009] BACKGROUND

[0010] Inflammatory bowel disease (IBD), which encompasses Crohn’s disease and ulcerative colitis (UC), is a chronic inflammatory disorder affecting about 1 .6 million people in the USA, and about 2.5-3 million people in Europe.

[0011] The aim of medical treatment in IBD is to control inflammation and reduce symptoms. Available treatment options for moderately to severely active UC include appropriate doses of oral corticosteroids; biologic therapies such as the tumor necrosis factor inhibitors (TNFi) infliximab, adalimumab, ustekinumab, and golimumab; the integrin receptor antagonist vedolizumab; and the orally administered small molecule Janus kinase inhibitor tofacitinib. However, non-response, inadequate 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) remains an unmet clinical need. Further, in many instances, available treatment options are designed for adult patients.

[0012] 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) with disease severity; for example, an association was observed between the rs11554257 SNP and medically refractory UC compared with healthy controls (Haritunians et al., Inflammatory Bowel Diseases’ 16: 1830-1840, 2010). TL1 A has been found to be upregulated in IBD tissue specimens, with level of expression corresponding to the severity of disease (Bamias et al., Clin Immunol; 137: 242-249, 2010). TL1 A promotes inflammation and intestinal fibrosis in IBD. Further, variants in TNFSF15 have been linked to the pathogenesis of several autoimmune diseases, including psoriasis, rheumatoid arthritis, and multiple sclerosis, implicating a broad role for TNFSF15 in human inflammatory diseases.

[0013] Binding of TL1 A to its receptor death receptor 3 (DR3) stimulates T cell-mediated signaling and cytokine production. Because increased cytokine production leads to chronic inflammation, inhibition of TL1 A is a promising therapeutic strategy for treatment of inflammatory diseases, including IBD.

[0014] Thus, there is a need in the art for methods of treating inflammatory bowel disease, including Crohn’s disease and ulcerative colitis, with anti-TNF-like ligand 1A (TL1A) antibody therapy in pediatric patients. The present disclosure addresses these needs.PATENT

[0015] Attorney Docket No: 50474-373WO3

[0016] Genentech Docket No: P39855-WO-1

[0017] SUMMARY

[0018] In one aspect, the disclosure provides a method of treating an inflammatory bowel disease (IBD) in a pediatric patient, the method comprising administering to the patient an effective amount of an anti-TNF-like ligand 1A (TL1A) antibody in a dosing regimen comprising an induction phase, wherein the induction phase comprises administration of only four doses of the anti-TL1 A antibody, wherein (i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose, wherein the anti-TL1 A antibody comprises the following complementarity-determining regions (CDRs): (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

[0019] In another aspect, the disclosure provides a method of treating an IBD in a pediatric patient, the method comprising administering to the patient an effective amount of an anti-TL1 A antibody in a dosing regimen comprising an induction phase and a maintenance phase, wherein (a) the induction phase comprises administration of only four doses of the anti-TL1 A antibody, wherein (i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and (b) the maintenance phase comprises administration of the anti-TL1 A antibody every four weeks, wherein the anti-TL1 A antibody comprises the following CDRs: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

[0020] In some aspects, in the induction phase, the anti-TL1 A antibody is administered intravenously at a dose of between 8 mg / kg and 16 mg / kg, and wherein the dose does not exceed 500 mg. In some aspects, the patient has a body weight of at least 10 kg and less than 35 kg and, in the induction phase, the anti-TL1 A antibody is administered intravenously at a dose of about 16 mg / kg, wherein the dose does not exceed 500 mg. In other aspects, the patient has a body weight of at least 10 kg and less than 35 kg and, in the induction phase, the anti-TL1 A antibody is administered intravenously at a dose of about 8 mg / kg, wherein the dose does not exceed 250 mg.

[0021] In some aspects, the patient has a body weight of at least 35 kg and, in the induction phase, the anti-TL1 A antibody is administered intravenously at a dose of about 500 mg. In other aspects, the patient has a body weight of at least 35 kg and, in the induction phase, the anti-TL1 A antibody is administered intravenously at a dose of about 250 mg.

[0022] In some aspects, the induction phase has a duration of about 12 weeks. In some aspects, (a) the first dose of the anti-TL1 A antibody is administered on about Day 1 of Week 0; (b) the second dose of thePATENT

[0023] Attorney Docket No: 50474-373WO3

[0024] Genentech Docket No: P39855-WO-1

[0025] anti-TL1 A antibody is administered on about Day 1 of Week 2; (c) the third dose of the anti-TL1 A antibody is administered on about Day 1 of Week 6; and (d) the fourth dose of the anti-TL1 A antibody is administered on about Day 1 of Week 10.

[0026] In some aspects, the dosing regimen further comprises a maintenance phase.

[0027] In some aspects, in the maintenance phase, the anti-TL1 A antibody is administered subcutaneously at a dose of between 50 mg and 450 mg. In some aspects, the patient has a body weight of at least 10 kg and less than 35 kg and, in the maintenance phase, the anti-TL1 A antibody is administered subcutaneously at a dose of about 150 mg. In other aspects, the patient has a body weight of at least 10 kg and less than 35 kg and, in the maintenance phase, the anti-TL1 A antibody is administered subcutaneously at a dose of about 50 mg. In some aspects, the patient has a body weight of at least 35 kg and, in the maintenance phase, the anti-TL1 A antibody is administered subcutaneously at a dose of about 450 mg. In other aspects, the patient has a body weight of at least 35 kg and, in the maintenance phase, the anti-TL1 A antibody is administered subcutaneously at a dose of about 150 mg.

[0028] In some aspects, the maintenance phase comprises at least two doses of the anti-TL1 A antibody. In some aspects, the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks. In some aspects, the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every two weeks.

[0029] In some aspects, the maintenance phase comprises (i) at least one interval in which the anti-TL1 A antibody is administered every four weeks and (ii) at least one interval in which the anti-TL1 A antibody is administered every two weeks. In some aspects, (i) the patient has a body weight of at least 10 kg and less than 35 kg and, in the at least one interval in which the anti-TL1 A antibody is administered every two weeks, the anti-TL1 A antibody is administered subcutaneously at a dose of about 150 mg; or (ii) the patient has a body weight of at least 35 kg and, in the at least one interval in which the anti-TL1 A antibody is administered every two weeks, the anti-TL1 A antibody is administered subcutaneously at a dose of about 450 mg

[0030] In some aspects, the maintenance phase comprises eleven doses of the anti-TL1 A antibody. In some aspects, the maintenance phase has a duration of about 40 weeks.

[0031] In some aspects, a corticosteroid is administered to the patient in the induction phase, and the dose of the corticosteroid is tapered during the induction phase. In some aspects, administration of the corticosteroid is discontinued during the dosing regimen. In some aspects, the corticosteroid is prednisone or an equivalent thereof, budesonide, or budesonide multi-matrix (MMX).

[0032] In some aspects, the first dose of the maintenance phase is administered about two weeks after administration of the fourth dose of the induction phase.

[0033] In some aspects, the dosing regimen has a duration of about 52 weeks. In some aspects, (a) the first dose of the induction phase is administered on about Day 1 of Week 0; (b) the second dose of the induction phase is administered on about Day 1 of Week 2; (c) the third dose of the induction phase is administered on about Day 1 of Week 6; (d) the fourth dose of the induction phase is administered on about Day 1 of Week 10; (e) the first dose of the maintenance phase is administered on about Day 1 of Week 12; and (f) the subsequent doses of the maintenance phase are administered on about Day 1 of Weeks 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52.PATENT

[0034] Attorney Docket No: 50474-373WO3

[0035] Genentech Docket No: P39855-WO-1

[0036] In some aspects, the closing regimen further comprises an extension phase comprising administration of one or more additional dosing cycles of the anti-TL1 A antibody. In some aspects, (a) the extension phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks; (b) the extension phase comprises subcutaneous administration of the anti-TL1 A antibody every two weeks; or (c) the extension phase comprises (i) at least one interval in which the anti-TL1 A antibody is administered every four weeks and (ii) at least one interval in which the anti-TL1 A antibody is administered every two weeks. In some aspects, the one or more dosing cycles of the extension phase are administered to the patient following disease worsening during the maintenance phase.

[0037] In some aspects, (i) the patient has a body weight of at least 10 kg and less than 35 kg and, in the at least one interval in which the anti-TL1 A antibody is administered every two weeks, the anti-TL1 A antibody is administered subcutaneously at a dose of about 150 mg; or (ii) the patient has a body weight of at least 35 kg and, in the at least one interval in which the anti-TL1 A antibody is administered every two weeks, the anti-TL1 A antibody is administered subcutaneously at a dose of about 450 mg,

[0038] In some aspects, the IBD is ulcerative colitis (UC). In some aspects, the UC is moderately to severely active ulcerative colitis. In some aspects, the patient has a modified Mayo score (mMS) of between 5 points and 9 points. In some aspects, the patient has a Mayo endoscopic score (ES) of 2 or 3.

[0039] In some aspects, the IBD is Crohn’s disease (CD). In some aspects, the CD is moderately to severely active CD. In some aspects, (a) the patient has a Simple Endoscopic Score for Crohn’s Disease (SES-CD) of equal to or greater than 6; or (b) the patient has isolated ileal disease only, and has an SES-CD of equal to or greater than 4. In some aspects, the patient has a pediatric Crohn’s disease activity index (PCDAI) that is at least 30.

[0040] In some aspects, the patient has previously been treated with a therapy for UC or CD and has experienced inadequate response to the therapy, loss of response to the therapy, and / or intolerance of the therapy. In some aspects, the therapy was a conventional therapy. In some aspects, the conventional therapy comprised administration of a steroid, an immunomodulator, or an oral aminosalicylate. In some aspects, the therapy was an advanced therapy. In some aspects, the advanced therapy comprised administration of an anti-tumor necrosis factor (TNF) agent, an anti-integrin agent, an anti-IL 12 / IL23 agent, a Janus kinase (JAK) inhibitor, or a sphingosine-1 -phosphate (S1 P) inhibitor.

[0041] In another aspect, the disclosure provides a method of treating UC in a pediatric patient having a body weight of at least 10 kg and less than 35 kg, the method comprising administering to the patient an effective amount of an anti-TL1 A antibody in a dosing regimen comprising an induction phase and a maintenance phase, wherein (a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 16 mg / kg, wherein the dose does not exceed 500 mg, wherein (i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and (b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks at a dose of about 150 mg, wherein the anti-TL1 A antibody comprises the following CDRs: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3; (b) a CDR-H2 comprising the aminoPATENT

[0042] Attorney Docket No: 50474-373WO3

[0043] Genentech Docket No: P39855-WO-1

[0044] acid sequence of SEQ ID NO: 4; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

[0045] In another aspect, the disclosure provides a method of treating UC in a pediatric patient having a body weight of at least 10 kg and less than 35 kg, the method comprising administering to the patient an effective amount of an anti-TL1 A antibody in a dosing regimen comprising an induction phase and a maintenance phase, wherein (a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 8 mg / kg, wherein the dose does not exceed 250 mg, wherein (i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and (b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks at a dose of about 50 mg, wherein the anti-TL1 A antibody comprises the following CDRs: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

[0046] In another aspect, the disclosure provides a method of treating UC in a pediatric patient having a body weight of at least 35 kg, the method comprising administering to the patient an effective amount of an anti-TL1 A antibody in a dosing regimen comprising an induction phase and a maintenance phase, wherein (a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 500 mg, wherein (i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and (b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks at a dose of about 450 mg, wherein the anti-TL1 A antibody comprises the following CDRs: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

[0047] In another aspect, the disclosure provides a method of treating UC in a pediatric patient having a body weight of at least 35 kg, the method comprising administering to the patient an effective amount of an anti-TL1 A antibody in a dosing regimen comprising an induction phase and a maintenance phase, wherein (a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 250 mg, wherein (i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and (b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks at a dose of about 150 mg,PATENT

[0048] Attorney Docket No: 50474-373WO3

[0049] Genentech Docket No: P39855-WO-1

[0050] wherein the anti-TL1 A antibody comprises the following CDRs: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

[0051] In some aspects, in a population of patients treated according to the method, the treating results in an increase in the proportion of patients who have achieved clinical remission at the end of the induction phase as compared to a reference population. In some aspects, the induction phase has a duration of about 12 weeks, and the treating results in an increase in the proportion of patients who have achieved clinical remission at Week 12.

[0052] In some aspects, in a population of patients treated according to the method, the treating results in an increase in the proportion of patients who have achieved clinical remission at the end of the maintenance phase as compared to a reference population. In some aspects, the dosing regimen has a duration of about 52 weeks, and the treating results in an increase in the proportion of patients who have achieved clinical remission at Week 52.

[0053] In some aspects, clinical remission is a modified Mayo Score (mMS) <2 with rectal bleeding score (RBS) of 0, stool frequency subscore (SFS) = 0 or 1 , and endoscopic subscore (ES) = 0 or 1 .

[0054] In another aspect, the disclosure provides a method of treating CD in a pediatric patient having a body weight of at least 10 kg and less than 35 kg, the method comprising administering to the patient an effective amount of an anti-TL1 A antibody in a dosing regimen comprising an induction phase and a maintenance phase, wherein (a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 16 mg / kg, wherein the dose does not exceed 500 mg, wherein (i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and (b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks at a dose of about 150 mg, wherein the anti-TL1 A antibody comprises the following CDRs: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

[0055] In another aspect, the disclosure provides a method of treating CD in a pediatric patient having a body weight of at least 10 kg and less than 35 kg, the method comprising administering to the patient an effective amount of an anti-TL1 A antibody in a dosing regimen comprising an induction phase and a maintenance phase, wherein (a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 8 mg / kg, wherein the dose does not exceed 250 mg, wherein (i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and (b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody everyPATENT

[0056] Attorney Docket No: 50474-373WO3

[0057] Genentech Docket No: P39855-WO-1

[0058] four weeks at a dose of about 50 mg, wherein the anti-TL1 A antibody comprises the following CDRs: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3; (b) a ODR-H2 comprising the amino acid sequence of SEQ ID NO: 4; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

[0059] In another aspect, the disclosure provides a method of treating CD in a pediatric patient having a body weight of at least 35 kg, the method comprising administering to the patient an effective amount of an anti-TL1 A antibody in a dosing regimen comprising an induction phase and a maintenance phase, wherein (a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 500 mg, wherein (i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and (b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks at a dose of about 450 mg, wherein the anti-TL1 A antibody comprises the following CDRs: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

[0060] In another aspect, the disclosure provides a method of treating CD in a pediatric patient having a body weight of at least 35 kg, the method comprising administering to the patient an effective amount of an anti-TL1 A antibody in a dosing regimen comprising an induction phase and a maintenance phase, wherein (a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 250 mg, wherein (i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and (b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks at a dose of about 150 mg, wherein the anti-TL1 A antibody comprises the following CDRs: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

[0061] In some aspects, in a population of patients treated according to the method, the treating results in an increase in the proportion of patients who have achieved clinical remission at the end of the induction phase as compared to a reference population. In some aspects, the induction phase has a duration of about 12 weeks, and the treating results in an increase in the proportion of patients who have achieved clinical remission at Week 12.

[0062] In some aspects, in a population of patients treated according to the method, the treating results in an increase in the proportion of patients who have achieved clinical remission at the end of thePATENT

[0063] Attorney Docket No: 50474-373WO3

[0064] Genentech Docket No: P39855-WO-1

[0065] maintenance phase as compared to a reference population. In some aspects, the dosing regimen has a duration of about 52 weeks, and the treating results in an increase in the proportion of patients who have achieved clinical remission at Week 52.

[0066] In some aspects, clinical remission is a pediatric Crohn’s disease activity index (PCDAI) of less than 10.

[0067] In some aspects, in a population of patients treated according to the method, the treating results in an increase in the proportion of patients who have achieved an endoscopic response at the end of the induction phase as compared to a reference population. In some aspects, the induction phase has a duration of about 12 weeks, and the treating results in an increase in the proportion of patients who have achieved an endoscopic response at Week 12.

[0068] In some aspects, in a population of patients treated according to the method, the treating results in an increase in the proportion of patients who have achieved an endoscopic response at the end of the maintenance phase as compared to a reference population. In some aspects, the dosing regimen has a duration of about 52 weeks, and the treating results in an increase in the proportion of patients who have achieved an endoscopic response at Week 52.

[0069] In some aspects, an endoscopic response is a Simple Endoscopic Score for Crohn’s Disease (SES-CD) that is at least 50% lower than a baseline SES-CD.

[0070] In some aspects, the reference population is a population of patients who have not been treated with an anti-TL1 A antibody.

[0071] In some aspects, the patient has been determined to be a haplotype B non-carrier for TNFSF15. In some aspects, the anti-TL1 A antibody comprises (a) a heavy chain variable (VH) domain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 1 ; and / or (b) a light chain variable (VL) domain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 2. In some aspects, the anti-TL1 A 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. In some aspects, the anti-TL1 A antibody comprises (a) a VH domain comprising the amino acid sequence of SEQ ID NO: 1 ; and (b) a VL domain comprising the amino acid sequence of SEQ ID NO: 2. In some aspects, the anti-TL1 A antibody comprises (a) a heavy chain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 9 or SEQ ID NO: 11 ; and / or (b) a light chain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 10. In some aspects, the anti-TL1 A antibody comprises (a) a heavy chain comprising the amino acid sequence of SEQ ID NO: 9; and / or (b) a light chain comprising the amino acid sequence of SEQ ID NO: 10. In some aspects, the anti-TL1 A antibody comprises (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. In some aspects, the anti-TL1 A antibody is afimkibart.

[0072] In another aspect, the disclosure provides a method of treating an inflammatory bowel disease (IBD) in a pediatric patient, the method comprising administering to the patient an effective amount of an anti-TNF-like ligand 1 A (TL1 A) antibody in a dosing regimen comprising an induction phase, wherein the induction phase comprises administration of only four doses of the anti-TL1 A antibody, wherein (i) thePATENT

[0073] Attorney Docket No: 50474-373WO3

[0074] Genentech Docket No: P39855-WO-1

[0075] second dose of the anti-TL1 A antibody is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; wherein the anti-TL1 A antibody comprises (a) a heavy chain comprising an amino acid sequence having the amino acid sequence of SEQ ID NO: 9; and (b) a light chain comprising an amino acid sequence having the amino acid sequence of SEQ ID NO: 10. In some aspects, the IBD is UC. In other aspects, the IBD is CD.

[0076] In another aspect, the disclosure provides a method of treating an IBD in a pediatric patient, the method comprising administering to the patient an effective amount of an anti-TL1 A antibody in a dosing regimen comprising an induction phase and a maintenance phase, wherein (a) the induction phase comprises administration of only four doses of the anti-TL1 A antibody, wherein (i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and (b) the maintenance phase comprises administration of the anti-TL1 A antibody every four weeks; wherein the anti-TL1 A antibody comprises (a) a heavy chain comprising an amino acid sequence having the amino acid sequence of SEQ ID NO: 9; and (b) a light chain comprising an amino acid sequence having the amino acid sequence of SEQ ID NO: 10. In some aspects, the IBD is UC. In other aspects, the IBD is CD.

[0077] In another aspect, the disclosure provides a kit comprising an anti-TNF-like ligand 1 A (TL1 A) antibody and a package insert comprising instructions for using the antibody for treating an inflammatory bowel disease (IBD) in a pediatric patient in need thereof according to the method of any one of the above aspects.

[0078] In another aspect, the disclosure provides an anti-TL1 A antibody for use in treating an IBD in a pediatric patient, wherein an effective amount of an anti-TL1 A antibody is to be administered to the patient in a dosing regimen comprising an induction phase, wherein the induction phase comprises administration of only four doses of the anti-TL1 A antibody, wherein (i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose, wherein the anti-TL1 A antibody comprises the following complementarity-determining regions (CDRs): (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

[0079] In another aspect, the disclosure provides an anti-TL1 A antibody for use in treating an IBD in a pediatric patient, wherein an effective amount of an anti-TL1 A antibody is to be administered to the patient in a dosing regimen comprising an induction phase and a maintenance phase, wherein (a) the induction phase comprises administration of only four doses of the anti-TL1 A antibody, wherein (i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and (b) thePATENT

[0080] Attorney Docket No: 50474-373WO3

[0081] Genentech Docket No: P39855-WO-1

[0082] maintenance phase comprises administration of the anti-TL1 A antibody every four weeks, wherein the anti-TL1 A antibody comprises the following CDRs: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

[0083] In another aspect, the disclosure provides an anti-TL1 A antibody for use in treating UC in a pediatric patient having a body weight of at least 10 kg and less than 35 kg, wherein an effective amount of the anti-TL1 A antibody is to be administered to the patient in a dosing regimen comprising an induction phase and a maintenance phase, wherein (a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 16 mg / kg, wherein the dose does not exceed 500 mg, wherein (i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and (b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks at a dose of about 150 mg, wherein the anti-TL1 A antibody comprises the following CDRs: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

[0084] In another aspect, the disclosure provides an anti-TL1 A antibody for use in treating UC in a pediatric patient having a body weight of at least 10 kg and less than 35 kg, wherein an effective amount of the anti-TL1 A antibody is to be administered to the patient in a dosing regimen comprising an induction phase and a maintenance phase, wherein (a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 8 mg / kg, wherein the dose does not exceed 250 mg, wherein (i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and (b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks at a dose of about 50 mg, wherein the anti-TL1 A antibody comprises the following CDRs: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

[0085] In another aspect, the disclosure provides an anti-TL1 A antibody for use in treating UC in a pediatric patient having a body weight of at least 35 kg, wherein an effective amount of an anti-TL1 A antibody is to be administered to the patient in a dosing regimen comprising an induction phase and a maintenance phase, wherein (a) the induction phase comprises intravenous administration of only fourPATENT

[0086] Attorney Docket No: 50474-373WO3

[0087] Genentech Docket No: P39855-WO-1

[0088] closes of the anti-TL1 A antibody at a dose of about 500 mg, wherein (i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and (b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks at a dose of about 450 mg, wherein the anti-TL1 A antibody comprises the following CDRs: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

[0089] In another aspect, the disclosure provides an anti-TL1 A antibody for use in treating UC in a pediatric patient having a body weight of at least 35 kg, wherein an effective amount of an anti-TL1 A antibody is to be administered to the patient in a dosing regimen comprising an induction phase and a maintenance phase, wherein (a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 250 mg, wherein (i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and (b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks at a dose of about 150 mg, wherein the anti-TL1 A antibody comprises the following CDRs: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

[0090] In another aspect, the disclosure provides an anti-TL1 A antibody for use in treating CD in a pediatric patient having a body weight of at least 10 kg and less than 35 kg, wherein an effective amount of the anti-TL1 A antibody is to be administered to the patient in a dosing regimen comprising an induction phase and a maintenance phase, wherein (a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 16 mg / kg, wherein the dose does not exceed 500 mg, wherein (i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and (b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks at a dose of about 150 mg, wherein the anti-TL1 A antibody comprises the following CDRs: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.PATENT

[0091] Attorney Docket No: 50474-373WO3

[0092] Genentech Docket No: P39855-WO-1

[0093] In another aspect, the disclosure provides an anti-TL1 A antibody for use in treating CD in a pediatric patient having a body weight of at least 10 kg and less than 35 kg, wherein an effective amount of the anti-TL1 A antibody is to be administered to the patient in a dosing regimen comprising an induction phase and a maintenance phase, wherein (a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 8 mg / kg, wherein the dose does not exceed 250 mg, wherein (i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and (b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks at a dose of about 50 mg, wherein the anti-TL1 A antibody comprises the following CDRs: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

[0094] In another aspect, the disclosure provides an anti-TL1 A antibody for use in treating CD in a pediatric patient having a body weight of at least 35 kg, wherein an effective amount of an anti-TL1 A antibody is to be administered to the patient in a dosing regimen comprising an induction phase and a maintenance phase, wherein (a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 500 mg, wherein (i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and (b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks at a dose of about 450 mg, wherein the anti-TL1 A antibody comprises the following CDRs: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

[0095] In another aspect, the disclosure provides an anti-TL1 A antibody for use in treating CD in a pediatric patient having a body weight of at least 35 kg, wherein an effective amount of an anti-TL1 A antibody is to be administered to the patient in a dosing regimen comprising an induction phase and a maintenance phase, wherein (a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 250 mg, wherein (i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and (b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks at a dose of about 150 mg, wherein the anti-TL1 A antibody comprises the following CDRs: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4; (c) aPATENT

[0096] Attorney Docket No: 50474-373WO3

[0097] Genentech Docket No: P39855-WO-1

[0098] CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

[0099] In another aspect, the disclosure provides an anti-TL1 A antibody for use in treating an IBD in a pediatric patient, wherein an effective amount of an anti-TL1 A antibody is to be administered to the patient in a dosing regimen comprising an induction phase, wherein the induction phase comprises administration of only four doses of the anti-TL1 A antibody, wherein (i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; wherein the anti-TL1 A antibody comprises (a) a heavy chain comprising an amino acid sequence having the amino acid sequence of SEQ ID NO: 9; and (b) a light chain comprising an amino acid sequence having the amino acid sequence of SEQ ID NO: 10.

[0100] In another aspect, the disclosure provides an anti-TL1 A antibody for use in treating an IBD in a pediatric patient, wherein an effective amount of an anti-TL1 A antibody is to be administered to the patient in a dosing regimen comprising an induction phase and a maintenance phase, wherein (a) the induction phase comprises administration of only four doses of the anti-TL1 A antibody, wherein (i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and (b) the maintenance phase comprises administration of the anti-TL1 A antibody every four weeks; wherein the anti-TL1 A antibody comprises (a) a heavy chain comprising an amino acid sequence having the amino acid sequence of SEQ ID NO: 9; and (b) a light chain comprising an amino acid sequence having the amino acid sequence of SEQ ID NO: 10.

[0101] In another aspect, the disclosure provides use of an anti-TL1 A antibody in the manufacture of a medicament for treating an IBD in a pediatric patient, wherein an effective amount of an anti-TL1 A antibody is to be administered to the patient in a dosing regimen comprising an induction phase, wherein the induction phase comprises administration of only four doses of the anti-TL1 A antibody, wherein (i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose, wherein the anti-TL1 A antibody comprises the following complementarity-determining regions (CDRs): (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

[0102] In another aspect, the disclosure provides use of an anti-TL1 A antibody in the manufacture of a medicament for treating an IBD in a pediatric patient, wherein an effective amount of an anti-TL1 A antibody is to be administered to the patient in a dosing regimen comprising an induction phase and a maintenance phase, wherein (a) the induction phase comprises administration of only four doses of the anti-TL1 A antibody, wherein (i) the second dose of the anti-TL1 A antibody is administered about twoPATENT

[0103] Attorney Docket No: 50474-373WO3

[0104] Genentech Docket No: P39855-WO-1

[0105] weeks after the first dose; (ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and (b) the maintenance phase comprises administration of the anti-TL1 A antibody every four weeks, wherein the anti-TL1 A antibody comprises the following CDRs: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

[0106] In another aspect, the disclosure provides use of an anti-TL1 A antibody in the manufacture of a medicament for treating UC in a pediatric patient having a body weight of at least 10 kg and less than 35 kg, wherein an effective amount of the anti-TL1 A antibody is to be administered to the patient in a dosing regimen comprising an induction phase and a maintenance phase, wherein (a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 16 mg / kg, wherein the dose does not exceed 500 mg, wherein (i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and (b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks at a dose of about 150 mg, wherein the anti-TL1 A antibody comprises the following CDRs: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

[0107] In another aspect, the disclosure provides use of an anti-TL1 A antibody in the manufacture of a medicament for treating UC in a pediatric patient having a body weight of at least 10 kg and less than 35 kg, wherein an effective amount of the anti-TL1 A antibody is to be administered to the patient in a dosing regimen comprising an induction phase and a maintenance phase, wherein (a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 8 mg / kg, wherein the dose does not exceed 250 mg, wherein (i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and (b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks at a dose of about 50 mg, wherein the anti-TL1 A antibody comprises the following CDRs: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

[0108] In another aspect, the disclosure provides use of an anti-TL1 A antibody in the manufacture of a medicament for treating UC in a pediatric patient having a body weight of at least 35 kg, wherein anPATENT

[0109] Attorney Docket No: 50474-373WO3

[0110] Genentech Docket No: P39855-WO-1

[0111] effective amount of an anti-TL1 A antibody is to be administered to the patient in a dosing regimen comprising an induction phase and a maintenance phase, wherein (a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 500 mg, wherein (i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and (b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks at a dose of about 450 mg, wherein the anti-TL1 A antibody comprises the following CDRs: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3; (b) a ODR-H2 comprising the amino acid sequence of SEQ ID NO: 4; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

[0112] In another aspect, the disclosure provides use of an anti-TL1 A antibody in the manufacture of a medicament for treating UC in a pediatric patient having a body weight of at least 35 kg, wherein an effective amount of an anti-TL1 A antibody is to be administered to the patient in a dosing regimen comprising an induction phase and a maintenance phase, wherein (a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 250 mg, wherein (i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and (b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks at a dose of about 150 mg, wherein the anti-TL1 A antibody comprises the following CDRs: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

[0113] In another aspect, the disclosure provides use of an anti-TL1 A antibody in the manufacture of a medicament for treating CD in a pediatric patient having a body weight of at least 10 kg and less than 35 kg, wherein an effective amount of the anti-TL1 A antibody is to be administered to the patient in a dosing regimen comprising an induction phase and a maintenance phase, wherein (a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 16 mg / kg, wherein the dose does not exceed 500 mg, wherein (i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and (b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks at a dose of about 150 mg, wherein the anti-TL1 A antibody comprises the following CDRs: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5; (d) a CDR-L1 comprising the amino acidPATENT

[0114] Attorney Docket No: 50474-373WO3

[0115] Genentech Docket No: P39855-WO-1

[0116] sequence of SEQ ID NO: 6; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

[0117] In another aspect, the disclosure provides use of an anti-TL1 A antibody in the manufacture of a medicament for treating CD in a pediatric patient in a pediatric patient having a body weight of at least 10 kg and less than 35 kg, wherein an effective amount of the anti-TL1 A antibody is to be administered to the patient in a dosing regimen comprising an induction phase and a maintenance phase, wherein (a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 8 mg / kg, wherein the dose does not exceed 250 mg, wherein (i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and (b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks at a dose of about 50 mg, wherein the anti-TL1 A antibody comprises the following CDRs: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

[0118] In another aspect, the disclosure provides use of an anti-TL1 A antibody in the manufacture of a medicament for treating CD in a pediatric patient having a body weight of at least 35 kg, wherein an effective amount of an anti-TL1 A antibody is to be administered to the patient in a dosing regimen comprising an induction phase and a maintenance phase, wherein (a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 500 mg, wherein: (i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and (b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks at a dose of about 450 mg, wherein the anti-TL1 A antibody comprises the following CDRs: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

[0119] In another aspect, the disclosure provides use of an anti-TL1 A antibody in the manufacture of a medicament for treating CD in a pediatric patient having a body weight of at least 35 kg, wherein an effective amount of an anti-TL1 A antibody is to be administered to the patient in a dosing regimen comprising an induction phase and a maintenance phase, wherein (a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 250 mg, wherein (i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and (b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody everyPATENT

[0120] Attorney Docket No: 50474-373WO3

[0121] Genentech Docket No: P39855-WO-1

[0122] four weeks at a dose of about 150 mg, wherein the anti-TL1 A antibody comprises the following CDRs: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3; (b) a ODR-H2 comprising the amino acid sequence of SEQ ID NO: 4; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

[0123] In another aspect, the disclosure provides use of an anti-TL1 A antibody in the manufacture of a medicament for treating an IBD in a pediatric patient, wherein an effective amount of an anti-TL1 A antibody is to be administered to the patient in a dosing regimen comprising an induction phase, wherein the induction phase comprises administration of only four doses of the anti-TL1 A antibody, wherein (i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; wherein the anti-TL1 A antibody comprises (a) a heavy chain comprising an amino acid sequence having the amino acid sequence of SEQ ID NO: 9; and (b) a light chain comprising an amino acid sequence having the amino acid sequence of SEQ ID NO: 10.

[0124] In another aspect, the disclosure provides use of an anti-TL1 A antibody in the manufacture of a medicament for treating an IBD in a pediatric patient, wherein an effective amount of an anti-TL1 A antibody is to be administered to the patient in a dosing regimen comprising an induction phase and a maintenance phase, wherein (a) the induction phase comprises administration of only four doses of the anti-TL1 A antibody, wherein (i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and (b) the maintenance phase comprises administration of the anti-TL1 A antibody every four weeks; wherein the anti-TL1 A antibody comprises (a) a heavy chain comprising an amino acid sequence having the amino acid sequence of SEQ ID NO: 9; and (b) a light chain comprising an amino acid sequence having the amino acid sequence of SEQ ID NO: 10.

[0125] BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 A is a schematic diagram showing the design of the induction phase of the CA45905 and CP45906 studies, which relate to treatment of pediatric patients having ulcerative colitis (UC) and Crohn’s disease (CD), respectively, with afimkibart, and a comparator study for adult patients in which afimkibart was administered at a dose of 500 mg intravenously (IV) on Weeks 0, 2, 6, and 10. Cave = average serum concentration; wk = week.

[0126] FIG. 1B is a plot showing predicted afimkibart exposure levels (average concentration over 12 weeks (Caverage, 12wk)) for (i) the “low body weight (BW), high dose” pediatric IV induction regimen (16 mg / kg afimkibart in patients having a BW >10 to <35 kg, wherein the dose does not exceed 500 mg); (ii) the “high body weight (BW), high dose” pediatric IV induction regimen (500 mg afimkibart in patients having a BW >35 kg); and (iii) a comparator adult IV induction regimen (500 mg afimkibart). The number and timing of doses for each regimen is shown in Fig. 1 A.PATENT

[0127] Attorney Docket No: 50474-373WO3

[0128] Genentech Docket No: P39855-WO-1

[0129] FIG.2A is a schematic diagram showing the design of the induction phase of the CA45905 and CP45906 studies, which relate to treatment of pediatric patients having UC and CD, respectively, with afimkibart, and a comparator study for adult patients in which afimkibart was administered at a dose of 150 mg subcutaneously (SC) on Weeks 0, 4, 8, and 12. IV = intravenous; Cave = average serum concentration; wk = week.

[0130] FIG.2B is a plot showing predicted afimkibart exposure levels (average concentration over 12 weeks (Caverage, 12wk)) for (i) the “low body weight (BW), low dose” pediatric IV induction regimen (8 mg / kg afimkibart in patients having a BW >10 to <35 kg, wherein the dose does not exceed 250 mg) and (ii) the “high body weight (BW), low dose” pediatric IV induction regimen (250 mg afimkibart in patients having a BW >35 kg) and predicted afimkibart exposure levels (average concentration over 14 weeks (Caverage, 14wk)) a comparator adult SC induction regimen (150 mg afimkibart). The number and timing of doses for each regimen is shown in Fig. 2A.

[0131] FIG. 3A is a schematic diagram showing the design of the maintenance phase of the CA45905 and CP45906 studies, which relate to treatment of pediatric patients having UC and CD, respectively, with afimkibart, and a comparator study for adult patients in which afimkibart was administered at a dose of 450 mg subcutaneously (SC) at the indicated times. Cave = average serum concentration; wk = week.

[0132] FIG. 3B is a plot showing predicted afimkibart exposure levels (average concentration over 40 weeks (Weeks 14-54) (Caverage)) for (i) the “low BW, high dose” pediatric SC maintenance regimen (150 mg afimkibart in patients having a BW >10 to <35 kg), (ii) the “high BW, high dose” pediatric SC maintenance regimen (450 mg afimkibart in patients having a BW >35 kg), and a comparator adult SC maintenance regimen (450 mg afimkibart). The number and timing of doses for each regimen is shown in Fig. 3A.

[0133] FIG.4A is a schematic diagram showing the design of the maintenance phase of the CA45905 and CP45906 studies, which relate to treatment of pediatric patients having UC and CD, respectively, with afimkibart, and a comparator study for adult patients in which afimkibart was administered at a dose of 150 mg subcutaneously (SC) at the indicated times. Cave = average serum concentration; wk = week.

[0134] FIG.4B is a plot showing predicted afimkibart exposure levels (average concentration over 40 weeks (Weeks 14-54) (Caverage)) for (i) the “low BW, low dose” pediatric SC maintenance regimen (50 mg afimkibart in patients having a BW >10 to <35 kg), (ii) the “high BW, high dose” pediatric SC maintenance regimen (150 mg afimkibart in patients having a BW >35 kg), and a comparator adult SC maintenance regimen (150 mg afimkibart). The number and timing of doses for each regimen is shown in Fig. 4A.

[0135] FIG. 5A is a schematic diagram showing a design for the pediatric Crohn’s disease (CD) study. BW = body weight; R= randomization; IV = intravenous; SC= subcutaneous; D = day; W = week; Q2W = every 2 weeks; Q4W = every 4 weeks; DWC = disease worsening criteria; OLE = open-label extension.

[0136] FIG. 5B is a schematic diagram showing the design of the pediatric ulcerative colitis (UC) study (CA45905 study) and a design for the pediatric Crohn’s disease (CD) study (CP45906 study). BW = body weight; R= randomization; IV = intravenous; SC= subcutaneous; D = day; W = week; Q2W = every 2 weeks; Q4W = every 4 weeks; DWC = disease worsening criteria; OLE = open-label extension.PATENT

[0137] Attorney Docket No: 50474-373WO3

[0138] Genentech Docket No: P39855-WO-1

[0139] FIG. 5C is a schematic diagram showing the design of the pediatric ulcerative colitis (UC) and Crohn’s disease (CD) studies (CA45905 and CP45906 studies), showing Cohorts 1 and 2. BW = body weight; IV = intravenous; SC= subcutaneous; W = week; PK = pharmacokinetics.

[0140] FIG.6 is a schematic diagram showing a comparison of the Phase 3 ulcerative colitis (UC) and Crohn’s disease (CD) adult studies to the Phase 2a (TUSCANY) and Phase 2b (TUSCANY-2) trials. The 12-week cumulative bioavailable dose (in mg) is shown. IV = intravenous; SC= subcutaneous; OL = open-label; Q4W = every 4 weeks; f-u = follow-up; mo = months.

[0141] FIG.7 is a set of graphs showing total pharmacokinetics (PK) (total drug concentration in the serum (in pg / mL)) of afimkibart in the induction phase dosing regimen of the Phase 2a (TUSCANY) trial (Ph2a (UC)), the 450 mg induction phase dosing regimen of the Phase 2b (TUSCANY-2) trial (Ph2B (UC)), and two induction phase dosing regimens for the Phase 3 adult trials discussed herein over time.

[0142] 4 x IV: afimkibart is administered intravenously (IV) at Weeks 0, 2, 6, and 10 of a 12-week dosing regimen, for a total of four doses. 5 x IV: afimkibart is administered IV at Weeks 0, 2, 4, 6, and 10 of a 12-week dosing regimen, for a total of five doses. The Phase 2a and Phase 2b plots present real data; the Phase 3 plots are modeled. In the modeled panels, solid lines show the median drug concentration, and dotted lines show the 90% confidence interval (Cl).

[0143] FIG.8 is a set of graphs showing levels of soluble TL1 A (sTL1 A) (in pg / mL) in the induction phase dosing regimen of the Phase 2a (TUSCANY) trial (Ph2a), the 450 mg induction phase dosing regimen of the Phase 2b (TUSCANY-2) trial (Ph2B), and two induction phase dosing regimens for the Phase 3 adult trials discussed herein over time. 4 x IV: afimkibart is administered intravenously (IV) at Weeks 0, 2, 6, and 10 of a 12-week dosing regimen, for a total of four doses. 5 x IV: afimkibart is administered IV at Weeks 0, 2, 4, 6, and 10 of a 12-week dosing regimen, for a total of five doses. The Phase 2a and Phase 2b plots present real data; the Phase 3 plots are modeled.

[0144] Fig.9A is graph showing predicted concentration-time plots (solid line: median; shaded area: 90% prediction interval (PI)) for pediatric participants having a body weight (BW / WT) > 35 kg receiving treatment according to the CA45905 or CP45906 study overlaid with predicted concentration-time plots for adult participants with UC in the Phase Ila Study B7541002. IV = intravenous; Q2W = every 2 weeks.

[0145] Fig.9B is graph showing predicted concentration-time plots (solid line: median; shaded area: 90% prediction interval (PI)) for pediatric participants having a body weight (BW / WT) > 10 to < 35 kg receiving treatment according to the CA45905 or CP45906 study overlaid with predicted concentrationtime plots for adult participants with UC in the Phase Ila Study B7541002. IV = intravenous; Q2W = every 2 weeks.

[0146] Fig. 10 is a graph showing simulated average concentration (Cavg) up to clinical readout for afimkibart in pediatric participants (Cavg, Weeks 0-12) receiving treatment according to the CA45905 or CP45906 study and for adult participants with UC (completed studies B7541002 and B7541007; Cavg, Weeks 0-14) in the induction phases of the respective studies. Q2W = every 2 weeks; Q4W = every 4 weeks; UC = ulcerative colitis; IV = intravenous; SC = subcutaneous; BW = body weight.

[0147] Fig. 11 is a graph showing predicted steady state trough concentration (Ctrough.ss) for afimkibart in pediatric participants receiving treatment according to the maintenance phase of the CA45905 orPATENT

[0148] Attorney Docket No: 50474-373WO3

[0149] Genentech Docket No: P39855-WO-1

[0150] CP45906 study and for adult participants with UC in study B7541007. Q2W = every 2 weeks; Q4W = every 4 weeks; UC = ulcerative colitis; SC = subcutaneous; BW = body weight.

[0151] Fig. 12A is a graph showing predicted maximum concentration at steady state (Cmax) for afimkibart in pediatric participants receiving treatment according to the dose intensification regimen of the CA45905 or CP45906 study (450 mg or 150 mg SC Q2W regimen based on body weight category) and for adult participants treated according to a Q2W dosing regimen. Q2W = every 2 weeks; IV = intravenous; SC = subcutaneous. Pediatric patients: (i) > 35 kg: 450 mg SC Q2W, (ii) > 10 kg to < 35 kg: 150 mg SC Q2W. Adult patients: 450 mg SC Q2W (dose intensification regimen in ongoing Phase 3 study in UC). Adult patients: 500 mg IV Q2W for 7 doses (Phase Ila study in UC).

[0152] Fig. 12B is a graph showing predicted average concentration over the dosing interval at steady state (Cavg) for afimkibart in pediatric participants receiving treatment according to the dose intensification regimen of the CA45905 or CP45906 study (450 mg or 150 mg SC Q2W regimen based on body weight category) and for adult participants treated according to a Q2W dosing regimen. Q2W = every 2 weeks; IV = intravenous; SC = subcutaneous. Pediatric patients: (i) > 35 kg: 450 mg SC Q2W, (ii) > 10 kg to < 35 kg: 150 mg SC Q2W. Adult patients: 450 mg SC Q2W (dose intensification regimen in ongoing Phase 3 study in UC). Adult patients: 500 mg IV Q2W for 7 doses (Phase Ila study in UC).

[0153] DETAILED DESCRIPTION

[0154] The present invention provides therapeutic methods and compositions for treatment of inflammatory bowel disease, e.g. ulcerative colitis (UC) and Crohn’s disease (e.g., moderately to severely active UC and CD) in pediatric patients. The invention is based, at least in part, on the discovery that immunotherapies including an anti-TL1 A agent (e.g., anti-TL1 A antibody) can be useful in the treatment of IBD in such patients. Compositions, uses, and kits involving such antibodies are also provided herein.

[0155] I. Definitions

[0156] It is to be understood that aspects and embodiments of the invention described herein include “comprising,” “consisting,” and “consisting essentially of” aspects and embodiments. As used herein, the singular form “a,” “an,” and “the” includes plural references unless indicated otherwise.

[0157] The term “about” as used herein refers to the usual error range for the respective value readily known to the skilled person in this technical field. Reference to “about” a value or parameter herein includes (and describes) aspects that are directed to that value or parameter per se. For example, description referring to “about X” includes description of “X.”

[0158] As used herein, the term “induction phase” refers to a series of one or more doses or dosing cycles (e.g., about 2-6 doses or dosing cycles) of one or more therapeutic agents (e.g., an anti-TL1 A agent (e.g., anti-TL1 A antibody) (e.g., afimkibart) administered to a subject, wherein the one or more doses or dosing cycles are optionally followed by a maintenance phase.

[0159] The term “maintenance phase” as used herein refers to a series of one or more doses or dosing cycles of one or more therapeutic agents (e.g., an anti-TL1 A agent (e.g., anti-TL1 A antibody) (e.g., afimkibart) that are administered to a subject subsequent to an induction phase with no relevant intervening surgery (i.e., no intervening surgery relating to the disease or condition intended to be treatedPATENT

[0160] Attorney Docket No: 50474-373WO3

[0161] Genentech Docket No: P39855-WO-1

[0162] by the one or more therapeutic agents). In some instances, the maintenance phase is initiated only if the subject did not experience disease progression or unacceptable toxicity during the induction phase. The induction phase and maintenance phase may or may not comprise use of the same therapeutic agents.

[0163] As used herein, “afimkibart” (also known as RO7790121 , RVT-3101 , or PF-06480605) is an antibody that binds tumor necrosis factor (TNF) superfamily protein TNF-like 1 A (TL1 A) and comprises the heavy chain sequence of SEQ ID NO: 9 and the light chain sequence of SEQ ID NO: 10.

[0164] The terms “antibody that binds to TL1 A” and “anti-TL1 A antibody” refer to an antibody that is capable of binding TL1 A with sufficient affinity such that the antibody is useful as a diagnostic and / or therapeutic agent in targeting TL1 A. In one aspect, the extent of binding of an anti-TL1 A antibody to an unrelated, non-TL1 A protein is less than about 10% of the binding of the antibody to TL1 A as measured, e.g., by surface plasmon resonance (SPR). In one aspect, an antibody that binds to TL1 A has a dissociation constant (KD) of < 1 pM, < 100 nM, < 10 nM, < 1 nM, < 0.1 nM, < 0.01 nM, or < 0.001 nM (e.g., 10'8M or less, e.g., from 108M to 10'13M, e.g., from 109M to 10'13M).The term “antibody” encompasses various antibody structures exhibiting the desired antigen-binding activity, including but not limited to: monoclonal antibodies, multispecific antibodies (e.g., bispecific antibodies) and antibody fragments.

[0165] The term “monoclonal antibody” as used herein refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e. the antibodies forming this population are essentially identical, except for possible post-translational modifications arising e.g. during manufacturing and / or storage. These antibodies are directed against the same epitope (or the same group of epitopes in the case of multispecific monoclonal antibodies, e.g. the same pair of epitopes in the case of bispecific monoclonal antibodies). This definition expressly excludes polyclonal antibody preparations which are mixtures of antibodies directed against different epitopes. Monoclonal antibodies in accordance with the present invention may be made by a variety of techniques, including but not limited to hybridoma methodology, recombinant DNA methods, phage-display methods, and methods utilizing transgenic animals containing all or part of the human immunoglobulin loci, such methods and other exemplary methods for making monoclonal antibodies being described herein.

[0166] The term “full-length antibody” refers to an antibody having the structure of an immunoglobulin comprising two light chains and two heavy chains, and comprising an Fc region as defined herein. In one aspect, the antibody is a full-length IgG 1 antibody.

[0167] A “human antibody” is one which possesses an amino acid sequence which corresponds to that of an antibody produced by a human or a human cell or derived from a non-human source that utilizes human antibody repertoires or other human antibody-encoding sequences. This definition of a human antibody specifically excludes a humanized antibody comprising non-human antigen-binding residues.

[0168] A “humanized” antibody refers to an antibody comprising amino acid residues from non-human CDRs and amino acid residues from human FRs. In one aspect, a humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the CDRs correspond to those of a non-human antibody, and all or substantially all of the FRs correspond to those of a human antibody. A humanized antibody optionally may comprise at least a portion of an antibody constant region derived from a human antibody. A “humanized form” of an antibody, e.g., a non-human antibody, refers to an antibody that has undergone humanization.PATENT

[0169] Attorney Docket No: 50474-373WO3

[0170] Genentech Docket No: P39855-WO-1

[0171] “Native antibodies” refer to naturally occurring immunoglobulin molecules with varying structures. For example, native IgG antibodies are heterotetrameric glycoproteins of about 150,000 daltons, composed of two identical light chains (LC) and two identical heavy chains (HC) that are disulfide-bonded. From N- to C-terminus, each heavy chain has a heavy chain variable domain (VH), also called a variable heavy domain or a heavy chain variable region, followed by three heavy chain constant domains (CH1 , CH2, and CH3). Similarly, from N- to C-terminus, each light chain has a light chain variable domain (VL), also called a variable light domain or a light chain variable region, followed by a light chain constant domain (CL).

[0172] An “antibody fragment” refers to a molecule other than a full-length antibody that comprises a portion of a full-length antibody that binds 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.

[0173] The term “variable region” or “variable domain” refers to the domain of an antibody heavy or light chain that is involved in binding the antibody to antigen. The variable domains of the heavy chain and light chain (VH and VL, respectively) of a native antibody generally have similar structures, with each domain comprising four conserved framework regions (FRs) and three complementary determining regions (CDRs). (See, e.g., Kindt et al. Kuby Immunology, 6thed., W.H. Freeman and Co., page 91 (2007)). A single VH or VL domain may be sufficient to confer antigen-binding specificity. Furthermore, antibodies that bind a particular antigen may be isolated using a VH or VL domain from an antibody that binds the antigen to screen a library of complementary VL or VH domains, respectively. See, e.g., Portolano et al., J. Immunol. 150:880-887 (1993); Clarkson et al., Nature 352:624-628 (1991).

[0174] Glutamine or glutamate residues at the N-terminus of antibody heavy or light chains may be converted to pyro-glutamate spontaneously (see e.g. 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)). Hence, variable domains disclosed herein which comprise either a glutamine (Q) or a glutamate (E) amino acid residue at the N-terminus of the antibody heavy or light chain, may comprise an N-terminal pyro-glutamate (pyroE) residue instead of the N-terminal Q or E residue. Likewise, antibody heavy chains or light chains disclosed herein which comprise either a glutamine (Q) or a glutamate (E) amino acid residue at the N-terminus, may comprise an N-terminal pyroglutamate (pyroE) residue instead of the N-terminal Q or E residue. Accordingly, for each antibody heavy chain, light chain, or variable domain sequence disclosed herein that contains an N-terminal Q or E residue, the corresponding sequence with an N-terminal pyroE residue is also encompassed.

[0175] A “human consensus framework” is a framework which represents the most commonly occurring amino acid residues in a selection of human immunoglobulin VL or VH framework sequences. Generally, the selection of human immunoglobulin VL or VH sequences is from a subgroup of variable domain sequences. Generally, the subgroup of sequences is a subgroup as in Kabat, E.A., 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 “Kabat 1991”). In one aspect, for the VL, the subgroup isPATENT

[0176] Attorney Docket No: 50474-373WO3

[0177] Genentech Docket No: P39855-WO-1

[0178] subgroup kappa I as in Kabat 1991. In one aspect, for the VH, the subgroup is subgroup III as in Kabat 1991.

[0179] The term “complementarity determining region” or “CDR” as used herein refers to each of the regions of an antibody variable domain which are hypervariable in sequence and which determine antigen binding specificity. Generally, antibodies comprise six CDRs: three in the VH (CDR-H1 , CDR-H2, CDR-H3), and three in the VL (CDR-L1 , CDR-L2, CDR-L3). CDRs are defined by a variety of methods / systems by those skilled in the art. These systems and / or definitions have been developed and refined over a number of years and include Kabat, Chothia, IMGT, AbM, and Contact. The Kabat definition is based on sequence variability and generally is the most commonly used. The Chothia definition is based on the location of the structural loop regions. 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 analyses of the available antibody crystal structures. Software programs (e.g., abYsis: http: / / www.abysis.org / abysis / sequence_input / key_annotation / key_annotation.cgi) are available and known to those of skill in the art for analysis of antibody sequences and determination of CDRs.

[0180] Exemplary CDRs herein include (numbering of amino acid residues according to the reference cited, i.e. Chothia numbering for the Chothia and Contact definition, Kabat numbering for the Kabat definition and IMGT numbering for the IMGT definition):

[0181] (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”);

[0182] (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”);

[0183] (c) antigen contacts 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

[0184] (d) CDRs occurring at amino acid residues 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”).

[0185] “Framework” or “FR” refers to variable domain residues other than complementary determining regions (CDRs). The FR of a variable domain generally consists of four FR domains: FR1 , FR2, FR3, and FR4. Accordingly, the CDR and FR sequences generally appear in the following sequence in VH (or VL): FR1-CDR-H1(CDR-L1)-FR2- CDR-H2(CDR-L2)-FR3- CDR-H3(CDR-L3)-FR4.

[0186] The “class” of an antibody refers to the type of constant domain or constant region possessed by its heavy chain. There are five major classes of antibodies: IgA, IgD, IgE, IgG, and IgM, and several of these may be further divided into subclasses (isotypes), e.g., IgG 1 , lgG2, lgG3, lgG4, Ig A1 , and lgA2. The heavy chain constant domains that correspond to the different classes of immunoglobulins are called a, 5, E, y, and p, respectively. The light chain of an antibody may be assigned to one of two types, called kappa (K) and lambda (A), based on the amino acid sequence of its constant domain.PATENT

[0187] Attorney Docket No: 50474-373WO3

[0188] Genentech Docket No: P39855-WO-1

[0189] The terms “constant region derived from human origin” or “human constant region” as used herein denotes a constant region of a human antibody, in particular a heavy chain constant region of a human antibody of the subclass lgG1 , lgG2, lgG3, or lgG4 and / or a light chain kappa or lambda constant region. Such constant regions are well known in the state of the art and e.g. described by Kabat 1991. Unless otherwise specified herein, numbering of amino acid residues in the constant region is according to the numbering system as described in Kabat 1991. Specifically, the Kabat numbering system (referred to as “numbering according to Kabat” or “Kabat numbering” herein; see pages 647-660 of Kabat 1991) is used for the light chain constant domain of kappa and lambda isotype, and the Kabat EU index numbering system (referred to as “numbering according to Kabat EU index” or “Kabat EU index numbering” herein, see pages 661-723 of Kabat 1991) is used for the heavy chain constant domains.

[0190] The term “Fc region” herein is used to define a C-terminal region of an immunoglobulin heavy chain that contains at least a portion of the constant region. The term includes native sequence Fc regions and variant Fc regions. In one aspect, a human IgG heavy chain Fc region extends from Cys226, or from Pro230, to the carboxyl-terminus of the heavy chain. However, antibodies produced by host cells may undergo post-translational cleavage of one or more, particularly one or two, amino acids from the C-terminus of the heavy chain. Therefore an antibody produced by a host cell by expression of a specific nucleic acid molecule encoding a full-length heavy chain may include the full-length heavy chain, or it may include a cleaved variant of the full-length heavy chain. This may be the case in particular where the final 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 the C-terminal glycine (Gly446) and lysine (Lys447), of the Fc region may or may not be present. Amino acid sequences of heavy chains including an Fc region are denoted herein without C-terminal lysine if not indicated otherwise. The corresponding sequence including a C-terminal lysine residue is also encompassed, however. Accordingly, in one aspect, a heavy chain including an Fc region as specified herein comprises an additional C-terminal lysine residue (K447, Kabat EU numbering). Also encompassed is the corresponding sequence without the C-terminal glycine residue. Accordingly, in one aspect, a heavy chain including an Fc region as specified 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 proline amide (P445-NH2, Kabat EU numbering). Unless otherwise specified herein, numbering of amino acid residues in the Fc region or heavy chain constant region is according to the EU numbering system, also called the EU index, as described in Kabat 1991.

[0191] “Effector functions” refer to those biological activities attributable to the Fc region of an antibody, which vary with the antibody isotype. Examples of antibody effector functions include: C1q binding, complement dependent cytotoxicity (CDC), Fc receptor binding, antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), down regulation of cell surface receptors (e.g., B cell receptor), and B cell activation.

[0192] “Affinity” refers to the strength of the sum total of noncovalent interactions between a single binding site of a molecule (e.g., an antibody) and its binding partner (e.g., an antigen). Unless indicated otherwise, as used herein, “binding affinity” refers to intrinsic binding affinity which reflects a 1 :1 interaction between members of a binding pair (e.g., antibody and antigen). The affinity of a molecule XPATENT

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[0195] for its partner Y can generally be represented by the dissociation constant (KD). Affinity can be measured by common methods known in the art, including those described herein. A preferred method for measuring affinity is Surface Plasmon Resonance (SPR).

[0196] An “isolated” antibody is one which has been separated from a component of its natural environment. In some aspects, an antibody is purified to greater than 95% or 99% purity as determined by, for example, electrophoretic (e.g., SDS-PAGE, isoelectric focusing (IEF), capillary electrophoresis) or chromatographic (e.g., ion exchange or reverse phase HPLC, affinity chromatography, size exclusion chromatography) methods. For a review of methods for assessment of antibody purity, see, e.g., Flatman et al., J. Chromatogr. B 848:79-87 (2007).

[0197] An “isolated” nucleic acid refers to a nucleic acid molecule that has been separated from a component of its natural environment. An isolated nucleic acid includes a nucleic acid molecule contained in cells that ordinarily contain the nucleic acid molecule, but the nucleic acid molecule is present extrachromosomally or at a chromosomal location that is different from its natural chromosomal location.

[0198] “Isolated nucleic acid encoding an antibody” refers to one or more nucleic acid molecules encoding antibody heavy and light chains (or fragments thereof), including such nucleic acid molecule(s) in a single vector or separate vectors, and such nucleic acid molecule(s) present at one or more locations in a host cell.

[0199] The term “vector,” as used herein, refers to a nucleic acid molecule capable of propagating another nucleic acid to which it is linked. The term includes the vector as a self-replicating nucleic acid structure as well as the vector incorporated into the genome of a host cell into which it has been introduced. Certain vectors are capable of directing the expression of nucleic acids to which they are operatively linked. Such vectors are referred to herein as “expression vectors”.

[0200] The terms “host cell,” “host cell line,” and “host cell culture” are used interchangeably and refer to cells into which exogenous nucleic acid has been introduced, including the progeny of such cells. Host cells include “transformants” and “transformed cells,” which include the primary transformed cell and progeny derived therefrom without regard to the number of passages. Progeny may not be completely identical in nucleic acid content to a parent cell, but may contain mutations. Mutant progeny that have the same function or biological activity as screened or selected for in the originally transformed cell are included herein. Suitable host cells may include, for example, CHO cells, HEK-293 cells, Expi293F cells, PER.C6 cells, NSO cells, lymphocytic cells, prokaryotic cells such as E. coli, and other eukaryotic hosts such as plant cells and fungi. Human host cells are included with the proviso that they are not used within the human body.

[0201] A “naked antibody” refers to an antibody that is not conjugated to a heterologous moiety (e.g., a cytotoxic moiety) or radiolabel. The naked antibody may be present in a pharmaceutical composition.

[0202] “Percent (%) amino acid sequence identity” with respect to a reference polypeptide sequence is defined as the percentage of amino acid residues in a candidate sequence that are identical with the amino acid residues in the reference polypeptide sequence, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity, and not considering any conservative substitutions as part of the sequence identity for the purposes of the alignment. AlignmentPATENT

[0203] Attorney Docket No: 50474-373WO3

[0204] Genentech Docket No: P39855-WO-1

[0205] for purposes of determining percent amino acid sequence identity can be achieved in various ways that are within the skill in the art, for instance, using publicly available computer software such as BLAST, BLAST-2, Clustal W, MegAlign (DNASTAR) software or the FASTA program package. Those skilled in the art can determine appropriate parameters for aligning sequences, including any algorithms needed to achieve maximal alignment over the full length of the sequences being compared. Alternatively, the percent identity values can be generated using the sequence comparison computer program ALIGN-2. The ALIGN-2 sequence comparison computer program was authored by Genentech, Inc., and the source code has been filed with user documentation in the U.S. Copyright Office, Washington D.C., 20559, where it is registered under U.S. Copyright Registration No. TXU510087 and is described in WO 2001 / 007611.

[0206] Unless otherwise indicated, for purposes herein, percent amino acid sequence identity values are generated using the ggsearch program of the FASTA package version 36.3.8c or later with a BLOSUM50 comparison matrix. The FASTA program package was authored by W. R. Pearson and D. J. Lipman (1988), “Improved Tools for Biological Sequence Analysis” Proc. Nat. Acad. Sci. 85:2444-2448; W. R. Pearson (1996) “Effective protein sequence comparison” Meth. Enzymol. 266:227- 258; and Pearson et. al. (1997) Genomics 46:24-36 and is publicly available from www.fasta.bioch.virginia.edu / fasta_www2 / fasta_down.shtml or www. ebi.ac.uk / Tools / sss / fasta.

[0207] Alternatively, a public server accessible at fasta.bioch.virginia.edu / fasta_www2 / index.cgi can be used to compare the sequences, using the ggsearch (global protein protein) program and default options (BLGSUM50; open: -10; ext: -2; Ktup = 2) to ensure a global, rather than local, alignment is performed. Percent amino acid identity is given in the output alignment header.

[0208] An “immunoconjugate” is an antibody conjugated to one or more heterologous molecule(s), including but not limited to one or more cytotoxic agent(s).

[0209] As used herein, the term “treatment” refers to clinical intervention in an attempt to alter the natural course of a disease during the course of clinical pathology. Desirable effects of treatment include decreasing the rate of disease progression, ameliorating or palliating the disease state, and remission or improved prognosis. For purposes of this disclosure, beneficial or desired clinical results include reduction or improvement in signs and symptoms of inflammatory bowel disease (IBD) (e.g., ulcerative colitis (UC) or Crohn’s disease (CD)), for example as compared to before administration of the anti-TL1 A agent (e.g., anti-TL1 A antibody).

[0210] An “effective amount” of an agent, e.g., a pharmaceutical composition, refers to an amount of the antibody or medicament effective, at dosages and for periods of time necessary, to achieve the desired treatment as defined above. In more specific aspects, an effective amount prevents, alleviates or ameliorates signs or symptoms of IBD, and / or prolongs the survival of the subject being treated. For prophylactic use, beneficial or desired results include eliminating or reducing the risk, lessening the severity, or delaying the outset of the disease, including biochemical, histological and / or behavioral symptoms of the disease, its complications and intermediate pathological phenotypes presenting during development of the disease. For therapeutic use, beneficial or desired results include clinical results such as reducing one or more signs or symptoms of IBD, decreasing the dose of other medications required to treat the disease, enhancing the effect of another medication, and / or delaying the progression of thePATENT

[0211] Attorney Docket No: 50474-373WO3

[0212] Genentech Docket No: P39855-WO-1

[0213] disease in patients. An effective dosage can be administered in one or more administrations. For purposes of this disclosure, an effective dosage of drug, compound, or pharmaceutical composition is an amount sufficient to accomplish prophylactic or therapeutic treatment either directly or indirectly. As is understood in the clinical context, an effective dosage of a drug, compound, or pharmaceutical composition may or may not be achieved in conjunction with another drug, compound, or pharmaceutical composition. Thus, an “effective dosage” may be considered in the context of administering one or more therapeutic agents, and a single agent may be considered to be given in an effective amount if, in conjunction with one or more other agents, a desirable result may be or is achieved.

[0214] Herein, an “effective amount” may refer to the amount of a therapeutic agent (e.g., an anti-TL1 A agent (e.g., anti-TL1 A antibody, e.g., afimkibart) or a combination of therapeutic agents (e.g., an anti-TL1 A antibody and one or more additional therapeutic agents)), that achieves a therapeutic result. In some examples, the effective amount of a therapeutic agent or a combination of therapeutic agents is the amount of the agent or of the combination of agents that achieves a clinical endpoint of clinical remission, clinical response (e.g., improved modified Mayo score (mMS) or partial modified Mayo score (pmMS)), endoscopic improvement, endoscopic remission, histologic-endoscopic mucosal improvement, histologic-endoscopic remission, and / or corticosteroid-free remission. Improvement (e.g., in terms of clinical remission) may be relative to a suitable reference treatment, for example, treatment that does not include the anti-TL1 A agent (e.g., anti-TL1 A antibody).

[0215] “Ameliorating” means a lessening or improvement of one or more signs or symptoms of IBD (e.g., UC or CD), for example as compared to not administering an anti-TL1 A agent (e.g., anti-TL1 A antibody) as described herein. “Ameliorating” also includes shortening or reduction in duration of a symptom.

[0216] The term “preventing” or “prevent” refers to (a) keeping a disorder from occurring or (b) delaying the onset of a disorder or onset of symptoms of a disorder.

[0217] Treatment “effectively improves” or “effectively reduces” when assessment of the sign or symptom of IBD is quantified via a clinical measure relative to baseline and during and / or after the treatment period. The difference between the clinical measure at baseline and during / after treatment is compared and used to determine whether the sign or symptom has improved and the treatment is effective. This comparison can include comparison to placebo or to one or more of the prior therapies.

[0218] A “patient,” an “individual,” or a "subject," used interchangeably herein, is a mammal. In one aspect, the individual or subject is a human. In one aspect, the individual is in need of treatment with the medicament or antibody disclosed herein. As used herein, the term “pediatric patient” or “pediatric subject” refers to a patient (e.g., a human patient) that is less than 18 years old. In some aspects, a pediatric patient is at least two years old and is no more than 17 years old. In some aspects, a pediatric patient is less than 17 years old.

[0219] The term “pharmaceutical composition” or “pharmaceutical formulation” refers to a preparation of the agent (e.g., antibody) and one or more pharmaceutically acceptable carriers or excipients.

[0220] A “pharmaceutically acceptable carrier” refers to an ingredient in a pharmaceutical composition or formulation, other than an active ingredient, which is nontoxic to a subject and includes, but is not limited to, a buffer, excipient, stabilizer, surfactant, and / or preservative.PATENT

[0221] Attorney Docket No: 50474-373WO3

[0222] Genentech Docket No: P39855-WO-1

[0223] The term “subcutaneous administration” refers to the administration of a substance into the subcutaneous layer.

[0224] II. Methods of Treating Inflammatory Bowel Disease with Anti-TL1A Antibodies

[0225] In some aspects, the disclosure provides a method of treating an inflammatory bowel disease (IBD) (e.g., ulcerative colitis (UC) or Crohn’s disease (CD)) in a pediatric patient (e.g., a human pediatric patient, e.g., a human patient having an age >2 years and <17 years), the method comprising administering to the patient an effective amount of an anti-TNF-like ligand 1 A (TL1 A) agent (e.g., anti-TL1 A antibody) (e.g., an anti-TL1 A antibody provided in Section III herein) in a dosing regimen comprising at least a first phase (e.g., an induction phase), wherein the first phase (e.g., induction phase) comprises administration of only four doses of the anti-TL1 A agent (e.g., anti-TL1 A antibody), wherein: (i) the second dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about four weeks after the third dose.

[0226] In some aspects, the disclosure provides a method of treating an IBD (e.g., UC or CD) in a pediatric patient (e.g., a human pediatric patient, e.g., a human patient having an age >2 years and <17 years), the method comprising administering to the patient an effective amount of an anti-TL1 A agent (e.g., anti-TL1 A antibody) (e.g., an anti-TL1 A antibody provided in Section III herein) in a dosing regimen comprising a first phase (e.g., an induction phase) and a second phase (e.g., a maintenance phase), wherein: (a) the first phase (e.g., induction phase) comprises administration of only four doses of the anti-TL1 A agent (e.g., anti-TL1 A antibody), wherein: (i) the second dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about four weeks after the third dose; and (b) the second phase (e.g., maintenance phase) comprises administration of the anti-TL1A agent (e.g., anti-TL1 A antibody) every four weeks. In some aspects, the anti-TL1 A antibody comprises the following complementarity-determining regions (CDRs): (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8. In some aspects, the anti-TL1 A antibody is afimkibart.

[0227] The disclosure also provides an anti-TL1 A agent (e.g., anti-TL1 A antibody) for use in treating IBD in a pediatric patient (e.g., a human pediatric patient, e.g., a human patient having an age >2 years and <17 years) according to the methods provided herein and use of an anti-TL1 A agent (e.g., anti-TL1 A antibody) in the manufacture of a medicament for treating IBD according to the methods provided herein.

[0228] As a general principle, the treatment of IBD with anti-TL1 A antibodies is described in PCT Publication No. WO 2021 / 260577 and in U.S. Patent Application Publication No. US 2023 / 0235070 A1 , which are incorporated herein by reference for all purposes.PATENT

[0229] Attorney Docket No: 50474-373WO3

[0230] Genentech Docket No: P39855-WO-1

[0231] The methods of treatment and related uses provided herein may include one, two, or all three of a first phase (e.g., an induction phase), a second phase (e.g., a maintenance phase), and an extension phase.

[0232] A. First Phase

[0233] Any of the methods for treating IBD provided herein may comprise administration of an anti-TL1 A agent (e.g., anti-TL1 A antibody) in at least a first phase (e.g., an induction phase). The induction phase may comprise administration of one or more doses of the anti-TL1 A agent (e.g., anti-TL1 A antibody) (e.g., may comprise administration of one, two, three, or four doses of the anti-TL1 A agent (e.g., anti-TL1 A antibody)).

[0234] In some aspects, the first phase (e.g., induction phase) comprises administration of four doses of the anti-TL1 A agent (e.g., anti-TL1 A antibody), wherein: (i) the second dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about four weeks after the third dose. In some aspects, the first phase (e.g., induction phase) has a duration of about 12 weeks, and (a) the first dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered on about Day 1 of Week 0 (e.g., Day 1 ±3 days); (b) the second dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered on about Day 1 of Week 2 (e.g., Day 1 ±3 days); (c) the third dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered on about Day 1 of Week 6 (e.g., Day 1 ±3 days); and (d) the fourth dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered on about Day 1 of Week 10 (e.g., Day 1 ±3 days). In some aspects, the first phase (e.g., induction phase) has a duration of about 12 weeks, and (a) the first dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered on Day 1 of Week 0; (b) the second dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered on Day 1 of Week 2; (c) the third dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered on Day 1 of Week 6; and / or (d) the fourth dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered on Day 1 of Week 10 (e.g., first phase (e.g., induction phase) doses according to one, two, three, or all four of (a), (b), (c), and (d) are administered). In some aspects, the first phase (e.g., induction phase) has a duration of about 12 weeks, and (a) the first dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered on Day 1 of Week 0; (b) the second dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered on Day 1 of Week 2; (c) the third dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered on Day 1 of Week 6; and (d) the fourth dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered on Day 1 of Week 10.

[0235] The first phase (e.g., induction phase) doses can be administered by any means. Preferably, the first phase (e.g., induction phase) doses are administered intravenously or subcutaneously.

[0236] Accordingly, in some aspects, the disclosure provides a method of treating an IBD (e.g., UC or CD) in a pediatric patient (e.g., a human pediatric patient, e.g., a human patient having an age >2 years and <17 years), the method comprising administering to the patient an effective amount of an anti-TL1A agent (e.g., anti-TL1 A antibody) (e.g., an anti-TL1 A antibody provided in Section III herein) in a dosing regimen comprising a first phase (e.g., an induction phase), wherein the first phase (e.g., inductionPATENT

[0237] Attorney Docket No: 50474-373WO3

[0238] Genentech Docket No: P39855-WO-1

[0239] phase) comprises intravenous administration of only four doses of the anti-TL1 A agent (e.g., anti-TL1 A antibody), wherein the first phase (e.g., induction phase) has a duration of about 12 weeks, and (a) the first dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered on Day 1 of Week 0; (b) the second dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered on Day 1 of Week 2; (c) the third dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered on Day 1 of Week 6; and (d) the fourth dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered on Day 1 of Week 10. In some aspects, the anti-TL1 A antibody comprises the following CDRs: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8. In some aspects, the anti-TL1 A antibody is afimkibart.

[0240] In some aspects, the disclosure provides a method of treating IBD (e.g., UC or CD) in a pediatric patient (e.g., a human pediatric patient, e.g., a human patient having an age >2 years and <17 years), the method comprising administering to the patient an effective amount of an anti-TL1 A antibody in a dosing regimen comprising a first phase (e.g., an induction phase), wherein the first phase (e.g., induction phase) comprises administration of only four doses of the anti-TL1 A antibody, wherein: (i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; wherein the anti-TL1 A antibody comprises (a) a heavy chain variable (VH) domain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 1 ; and / or (b) a light chain variable (VL) domain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 2.

[0241] In some aspects, the disclosure provides a method of treating IBD (e.g., UC or CD) in a pediatric patient (e.g., a human pediatric patient, e.g., a human patient having an age >2 years and <17 years), the method comprising administering to the patient an effective amount of an anti-TL1 A antibody in a dosing regimen comprising a first phase (e.g., an induction phase), wherein the first phase (e.g., induction phase) comprises administration of only four doses of the anti-TL1 A antibody, wherein: (i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; wherein the anti-TL1 A antibody comprises (I) a heavy chain variable (VH) domain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 1 and / or (II) a light chain variable (VL) domain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 2, and comprises the following CDRs: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.PATENT

[0242] Attorney Docket No: 50474-373WO3

[0243] Genentech Docket No: P39855-WO-1

[0244] In some aspects, the disclosure provides a method of treating IBD (e.g., UC or CD) in a pediatric patient (e.g., a human pediatric patient, e.g., a human patient having an age >2 years and <17 years), the method comprising administering to the patient an effective amount of an anti-TL1 A antibody in a dosing regimen comprising administration of only four IV doses of the anti-TL1 A antibody, wherein: (i) the second IV dose of the anti-TL1 A antibody is administered about two weeks after the first dose; (ii) the third IV dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and (iii) the fourth IV dose of the anti-TL1 A antibody is administered about four weeks after the third dose; wherein the anti-TL1 A antibody comprises (a) a VH domain comprising an amino acid sequence having at least 95% sequence identity to 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 to the amino acid sequence of SEQ ID NO: 2.

[0245] In some aspects, the disclosure provides a method of treating IBD (e.g., UC or CD) in a pediatric patient (e.g., a human pediatric patient, e.g., a human patient having an age >2 years and <17 years), the method comprising administering to the patient an effective amount of an anti-TL1 A antibody in a dosing regimen comprising a first phase (e.g., an induction phase), wherein the first phase (e.g., induction phase) comprises administration of only four doses of the anti-TL1 A antibody, wherein: (i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; wherein the anti-TL1 A 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.

[0246] In some aspects, the disclosure provides a method of treating IBD (e.g., UC or CD) in a pediatric patient (e.g., a human pediatric patient, e.g., a human patient having an age >2 years and <17 years), the method comprising administering to the patient an effective amount of an anti- TL1 A antibody in a dosing regimen comprising a first phase (e.g., an induction phase), wherein the first phase (e.g., induction phase) comprises administration of only four doses of the anti-TL1 A antibody, wherein: (i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; wherein the anti-TL1 A antibody comprises (a) a heavy chain comprising an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 9; and (b) a light chain comprising an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 10. In some aspects, the anti-TL1A antibody is afimkibart.

[0247] In some aspects, the disclosure provides a method of treating IBD (e.g., UC or CD) in a pediatric patient (e.g., a human pediatric patient, e.g., a human patient having an age >2 years and <17 years), the method comprising administering to the patient an effective amount of an anti-TL1 A antibody in a dosing regimen comprising a first phase (e.g., an induction phase), wherein the first phase (e.g., induction phase) comprises administration of only four doses of the anti-TL1 A antibody, wherein: (i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; wherein the anti-TL1 APATENT

[0248] Attorney Docket No: 50474-373WO3

[0249] Genentech Docket No: P39855-WO-1

[0250] antibody comprises (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.

[0251] Intravenous Doses

[0252] In some aspects, in the first phase (e.g., induction phase), the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered intravenously (IV) at a dose of between 8 mg / kg and 16 mg / kg (e.g., at a dose of 8-10, 10-12, 12-14, or 14-16 mg / kg), wherein the dose does not exceed 500 mg (e.g., each dose in the first phase (e.g., induction phase) comprises IV administration of between 8 mg / kg and 16 mg / kg, and not more than 500 mg, of the anti-TL1 A agent (e.g., anti-TL1 A antibody)).

[0253] In some aspects, in the first phase (e.g., induction phase), (i) the patient has a body weight of at least 10 kg and less than 31 .25 kg and the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered intravenously at a dose of between 8 mg / kg and 16 mg / kg; or (ii) the patient has a body weight of at least 31 .25 kg and less than 35 kg and the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered intravenously at a dose of 250 mg or 500 mg.

[0254] Low Body Weight Dosing

[0255] In some aspects, in the first phase (e.g., induction phase), the patient (e.g., pediatric patient, e.g., human patient having an age >2 years and <17 years) has a body weight of at least 10 kg and less than 35 kg and the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered intravenously at a dose of about 16 mg / kg (e.g., is administered at a dose of 16 mg / kg), wherein the dose does not exceed 500 mg.

[0256] In some aspects, in the first phase (e.g., induction phase), the patient (e.g., pediatric patient, e.g., human patient having an age >2 years and <17 years) has a body weight of at least 10 kg and less than 35 kg and (i) the patient has a body weight of at least 10 kg and less than 31 .25 kg and the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered intravenously at a dose of about 16 mg / kg (e.g., is administered at a dose of 16 mg / kg); or (ii) the patient has a body weight of at least 31 .25 kg and less than 35 kg and the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered intravenously at a dose of about 500 mg (e.g., is administered at a dose of 500 mg).

[0257] In some aspects, the disclosure provides a method of treating an IBD (e.g., UC or CD) in a pediatric patient (e.g., a human pediatric patient, e.g., a human patient having an age >2 years and <17 years), the method comprising administering to the patient an effective amount of an anti-TL1 A agent (e.g., anti-TL1 A antibody) (e.g., an anti-TL1 A antibody provided in Section III herein) in a dosing regimen comprising intravenous (IV) administration of only four doses of the anti-TL1 A agent (e.g., anti-TL1 A antibody) at a dose of about 16 mg / kg (e.g., at a dose of 16 mg / kg), wherein the dose does not exceed 500 mg, wherein the four doses of the anti-TL1 A agent (e.g., anti-TL1 A antibody) are administered over about 12 weeks, and (a) the IV first dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered on Day 1 of Week 0; (b) the second IV dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered on Day 1 of Week 2; (c) the third IV dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered on Day 1 of Week 6; and (d) the fourth IV dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered on Day 1 of Week 10. In some aspects, the anti-TL1 A antibody comprises the following CDRs: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3; (b) a CDR-H2PATENT

[0258] Attorney Docket No: 50474-373WO3

[0259] Genentech Docket No: P39855-WO-1

[0260] comprising the amino acid sequence of SEQ ID NO: 4; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8. In some aspects, the anti-TL1 A antibody is afimkibart.

[0261] In some aspects, in the first phase (e.g., induction phase), the patient (e.g., pediatric patient, e.g., human patient having an age >2 years and <17 years) has a body weight of at least 10 kg and less than 35 kg and the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered intravenously at a dose of about 8 mg / kg (e.g., is administered at a dose of 8 mg / kg), wherein the dose does not exceed 250 mg.

[0262] In some aspects, in the first phase (e.g., induction phase), the patient (e.g., pediatric patient, e.g., human patient having an age >2 years and <17 years) has a body weight of at least 10 kg and less than 35 kg and (i) the patient has a body weight of at least 10 kg and less than 31 .25 kg and the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered intravenously at a dose of about 8 mg / kg (e.g., is administered at a dose of 8 mg / kg); or (ii) the patient has a body weight of at least 31 .25 kg and less than 35 kg and the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered intravenously at a dose of about 250 mg (e.g., is administered at a dose of 250 mg).

[0263] In some aspects, the disclosure provides a method of treating an IBD (e.g., UC or CD) in a pediatric patient (e.g., a human pediatric patient, e.g., a human patient having an age >2 years and <17 years), the method comprising administering to the patient an effective amount of an anti-TL1 A agent (e.g., anti-TL1 A antibody) (e.g., an anti-TL1 A antibody provided in Section III herein) in a dosing regimen comprising intravenous (IV) administration of only four doses of the anti-TL1 A agent (e.g., anti-TL1 A antibody) at a dose of about 8 mg / kg (e.g., at a dose of 8 mg / kg), wherein the dose does not exceed 250 mg, wherein the four doses of the anti-TL1 A agent (e.g., anti-TL1 A antibody) are administered over about 12 weeks, and (a) the IV first dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered on Day 1 of Week 0; (b) the second IV dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered on Day 1 of Week 2; (c) the third IV dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered on Day 1 of Week 6; and (d) the fourth IV dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered on Day 1 of Week 10. In some aspects, the anti-TL1 A antibody comprises the following CDRs: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8. In some aspects, the anti-TL1 A antibody is afimkibart.

[0264] High Body Weight Dosing

[0265] In some aspects, in the first phase (e.g., induction phase), the patient (e.g., pediatric patient, e.g., human patient having an age >2 years and <17 years) has a body weight of at least 35 kg and the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered intravenously at a dose of about 500 mg (e.g., is administered at a dose of 500 mg).

[0266] In some aspects, the disclosure provides a method of treating an IBD (e.g., UC or CD) in a pediatric patient (e.g., a human pediatric patient, e.g., a human patient having an age >2 years and <17PATENT

[0267] Attorney Docket No: 50474-373WO3

[0268] Genentech Docket No: P39855-WO-1

[0269] years), the method comprising administering to the patient an effective amount of an anti-TL1 A agent (e.g., anti-TL1 A antibody) (e.g., an anti-TL1 A antibody provided in Section III herein) in a dosing regimen comprising intravenous (IV) administration of only four doses of the anti-TL1 A agent (e.g., anti-TL1 A antibody) at a dose of about 500 mg (e.g., at a dose of 500 mg), wherein the four doses of the anti-TL1 A agent (e.g., anti-TL1 A antibody) are administered over about 12 weeks, and (a) the IV first dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered on Day 1 of Week 0; (b) the second IV dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered on Day 1 of Week 2; (c) the third IV dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered on Day 1 of Week 6; and (d) the fourth IV dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered on Day 1 of Week 10. In some aspects, the anti-TL1 A antibody comprises the following CDRs: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8. In some aspects, the anti-TL1 A antibody is afimkibart.

[0270] In some aspects, in the first phase (e.g., induction phase), the patient (e.g., pediatric patient, e.g., human patient having an age >2 years and <17 years) has a body weight of at least 35 kg and the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered intravenously at a dose of about 250 mg (e.g., is administered at a dose of 250 mg).

[0271] In some aspects, the disclosure provides a method of treating an IBD (e.g., UC or CD) in a pediatric patient (e.g., a human pediatric patient, e.g., a human patient having an age >2 years and <17 years), the method comprising administering to the patient an effective amount of an anti-TL1 A agent (e.g., anti-TL1 A antibody) (e.g., an anti-TL1 A antibody provided in Section III herein) in a dosing regimen comprising intravenous (IV) administration of only four doses of the anti-TL1 A agent (e.g., anti-TL1 A antibody) at a dose of about 250 mg (e.g., at a dose of 250 mg), wherein the four doses of the anti-TL1 A agent (e.g., anti-TL1 A antibody) are administered over about 12 weeks, and (a) the IV first dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered on Day 1 of Week 0; (b) the second IV dose of the anti-TL1 A antibody is administered on Day 1 of Week 2; (c) the third IV dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered on Day 1 of Week 6; and (d) the fourth IV dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered on Day 1 of Week 10. In some aspects, the anti-TL1 A antibody comprises the following CDRs: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8. In some aspects, the anti-TL1 A antibody is afimkibart.

[0272] B. Second Phase

[0273] Any of the methods provided herein may comprise administration of an anti-TL1 A agent (e.g., anti-TL1 A antibody) in a second phase (e.g., a maintenance phase) that follows administration of the anti-TL1 A agent (e.g., anti-TL1 A antibody) in a first phase (e.g., an induction phase). The second phase (e.g.,PATENT

[0274] Attorney Docket No: 50474-373WO3

[0275] Genentech Docket No: P39855-WO-1

[0276] maintenance phase) may comprise administration of one or more doses of the anti-TL1 A agent (e.g., anti-TL1 A antibody).

[0277] The second phase (e.g., maintenance phase) may be initiated at any appropriate time following the first phase (e.g., induction phase). In some aspects, the first dose of the second phase (e.g., maintenance phase) is administered about two weeks (e.g., two weeks) after administration of the last dose of the first phase (e.g., induction phase). For example, in aspects in which the first phase (e.g., induction phase) comprises administration of four doses of the anti-TL1 A agent (e.g., anti-TL1 A antibody), the first dose of the second phase (e.g., maintenance phase) may be administered about two weeks (e.g., two weeks) after administration of the fourth dose of the first phase (e.g., induction phase).

[0278] In some aspects in which the second phase (e.g., maintenance phase) comprises administration of at least two doses of the anti-TL1 A agent (e.g., anti-TL1 A antibody), the time interval between each individual dose in the second phase (e.g., maintenance dose) may be the same. In other aspects, the time interval between individual doses in the second phase (e.g., maintenance phase doses) is not the same. The individual doses in the second phase (e.g., maintenance phase) can be administered at least daily, at least one day apart, at least 1 week apart, at least 2 weeks apart, at least 3 weeks apart, at least 1 month apart, at least 2 months apart, at least 3 months apart, at least 4 months apart, at least 5 months apart, or at least 6 months apart. In one preferred aspect, the individual doses in the second phase (e.g., maintenance doses) are administered one month apart.

[0279] In some aspects, the second phase (e.g., maintenance phase) comprises administration (e.g., subcutaneous administration) of the anti-TL1 A agent (e.g., anti-TL1 A antibody) every four weeks (Q4W).

[0280] In some aspects, the second phase (e.g., maintenance phase) comprises administration (e.g., subcutaneous administration) of the anti-TL1 A agent (e.g., anti-TL1 A antibody) every two weeks (Q2W).

[0281] In some aspects, the second phase (e.g., maintenance phase) comprises (i) at least one interval in which the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered every four weeks (Q4W) and (ii) at least one interval in which the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered every two weeks (Q2W). In some aspects, the second phase (e.g., maintenance phase) dosing frequency of a subject is increased from Q4W to Q2W based on observation of disease worsening (“dose intensification”). In some aspects, the disease worsening is (i) rectal bleeding score > 2 on at least three days within the past seven days, excluding any days coinciding with bowel preparation and endoscopy, and (ii) endoscopic score (ES) >2, based on central reading (if endoscopy was conducted within > 6 weeks). In some aspects, the disease worsening is calprotectin >150pg / g. In some aspects, participants continue the intensified Q2W SC dosing schedule for a period of 12 weeks, then return to Q4W SC dosing.

[0282] Doses in the second (e.g., maintenance) phase can be administered by any means (e.g., may be administered intravenously or subcutaneously). For example, in some aspects, in the second (e.g., maintenance) phase, the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered subcutaneously. In some aspects, the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered subcutaneously every four weeks (Q4W).

[0283] In some aspects, the second phase (e.g., maintenance phase) comprises administration of 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 doses of the anti-TL1 A agent (e.g., anti-TL1 A antibody). In some aspects, the dosing regimen has aPATENT

[0284] Attorney Docket No: 50474-373WO3

[0285] Genentech Docket No: P39855-WO-1

[0286] duration of about 52 weeks, the first dose of the maintenance phase is administered on about Day 1 of Week 12, and the subsequent doses of the maintenance phase are administered on about Day 1 of Weeks 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52.

[0287] In some aspects, the second phase (e.g., maintenance phase) comprises eleven doses of the anti-TL1 A agent (e.g., anti-TL1 A antibody) (e.g., comprises eleven doses of the anti-TL1 A agent (e.g., anti-TL1 A antibody) administered in a Q4W dosing regimen). In some aspects, the second phase (e.g., maintenance phase) has a duration of about 40 weeks.

[0288] Accordingly, in some aspects, the disclosure provides a method of treating an IBD (e.g., UC or CD) in a pediatric patient (e.g., a human pediatric patient, e.g., a human patient having an age >2 years and <17 years), the method comprising administering to the patient an effective amount of an anti-TL1 A agent (e.g., anti-TL1 A antibody) (e.g., an anti-TL1 A antibody provided in Section III herein) in a dosing regimen comprising a first phase (e.g., an induction phase) and a second phase (e.g., a maintenance phase), wherein (a) the first phase (e.g., induction phase) comprises intravenous administration of only four doses of the anti-TL1 A agent (e.g., anti-TL1 A antibody), wherein the first phase (e.g., induction phase) has a duration of about 12 weeks, wherein (a) the induction phase comprises administration of only four doses of the anti-TL1 A agent (e.g., anti-TL1 A antibody), wherein: (i) the second dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about four weeks after the third dose; and (b) the maintenance phase comprises administration of the anti-TL1 A agent (e.g., anti-TL1 A antibody) every four weeks. In some aspects, the anti-TL1 A antibody comprises the following CDRs: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8. In some aspects, the anti-TL1 A antibody is afimkibart.

[0289] In some aspects, the disclosure provides a method of treating an IBD (e.g., UC or CD) in a pediatric patient (e.g., a human pediatric patient, e.g., a human patient having an age >2 years and <17 years), the method comprising administering to the patient an effective amount of an anti-TL1 A antibody in a dosing regimen comprising an induction phase and a maintenance phase, wherein: (a) the induction phase comprises administration of only four doses of the anti-TL1 A antibody, wherein: (i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and (b) the maintenance phase comprises administration of the anti-TL1 A antibody every four weeks; wherein the anti-TL1 A antibody comprises: (a) a heavy chain comprising an amino acid sequence having the amino acid sequence of SEQ ID NO: 9; and (b) a light chain comprising an amino acid sequence having the amino acid sequence of SEQ ID NO: 10.PATENT

[0290] Attorney Docket No: 50474-373WO3

[0291] Genentech Docket No: P39855-WO-1

[0292] Subcutaneous Doses

[0293] In some aspects, in the second phase (e.g., maintenance phase), the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered subcutaneously (SC) at a dose of between 50 mg and 450 mg (e.g., at a dose of 50-75, 75-100, 100-125, 125-150, 150-200, 200-225, 225-250, 250-275, 275-300, 300-325, 325-350, 350-375, 375-400, 400-425, or 425-450 mg), e.g., each dose in the second phase (e.g., maintenance phase) comprises IV administration of between 50 mg and 450 mg of the anti-TL1 A agent (e.g., anti-TL1 A antibody)).

[0294] Low Body Weight Dosing

[0295] In some aspects, in the second phase (e.g., maintenance phase), the patient (e.g., pediatric patient, e.g., human patient having an age >2 years and <17 years) has a body weight of at least 10 kg and less than 35 kg and the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered subcutaneously at a dose of about 150 mg (e.g., at a dose of 150 mg).

[0296] In some aspects, the disclosure features a method of treating an IBD (e.g., UC or CD) in a pediatric patient (e.g., a human pediatric patient, e.g., a human patient having an age >2 years and <17 years) having a body weight of at least 10 kg and less than 35 kg, the method comprising administering to the patient an effective amount of an anti-TL1 A agent (e.g., anti-TL1 A antibody) in a dosing regimen comprising a first phase (e.g., an induction phase) and a second phase (e.g., a maintenance phase), wherein (a) the first phase (e.g., induction phase) comprises intravenous administration of only four doses of the anti-TL1 A agent (e.g., anti-TL1 A antibody) at a dose of about 16 mg / kg (e.g., at a dose of 16 mg / kg), wherein the dose does not exceed 500 mg, wherein (i) the second dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about four weeks after the third dose; and (b) the second phase (e.g., maintenance phase) comprises subcutaneous administration of the anti-TL1A agent (e.g., anti-TL1A antibody) every four weeks at a dose of about 150 mg.

[0297] In some aspects, in the second phase (e.g., maintenance phase), the patient (e.g., pediatric patient, e.g., human patient having an age >2 years and <17 years) has a body weight of at least 10 kg and less than 35 kg and the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered subcutaneously at a dose of about 50 mg (e.g., at a dose of 50 mg).

[0298] In some aspects, the disclosure features a method of treating an IBD (e.g., UC or CD) in a pediatric patient (e.g., a human pediatric patient, e.g., a human patient having an age >2 years and <17 years) having a body weight of at least 10 kg and less than 35 kg, the method comprising administering to the patient an effective amount of an anti-TL1 A agent (e.g., anti-TL1 A antibody) in a dosing regimen comprising a first phase (e.g., an induction phase) and a second phase (e.g., a maintenance phase), wherein (a) the first phase (e.g., induction phase) comprises intravenous administration of only four doses of the anti-TL1 A agent (e.g., anti-TL1 A antibody) at a dose of about 8 mg / kg (e.g., at a dose of 8 mg / kg), wherein the dose does not exceed 250 mg, wherein (i) the second dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 APATENT

[0299] Attorney Docket No: 50474-373WO3

[0300] Genentech Docket No: P39855-WO-1

[0301] agent (e.g., anti-TL1 A antibody) is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about four weeks after the third dose; and (b) the second phase (e.g., maintenance phase) comprises subcutaneous administration of the anti-TL1 A agent (e.g., anti-TL1 A antibody) every four weeks at a dose of about 50 mg.

[0302] High Body Weight Dosing

[0303] In some aspects, in the second phase (e.g., maintenance phase), the patient (e.g., pediatric patient, e.g., human patient having an age >2 years and <17 years) has a body weight of at least 35 kg and the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered subcutaneously at a dose of about 450 mg (e.g., at a dose of 450 mg).

[0304] In some aspects, the disclosure features a method of treating an IBD (e.g., UC or CD) in a pediatric patient (e.g., a human pediatric patient, e.g., a human patient having an age >2 years and <17 years) having a body weight of at least 35 kg, the method comprising administering to the patient an effective amount of an anti-TL1 A agent (e.g., anti-TL1 A antibody) in a dosing regimen comprising a first phase (e.g., an induction phase) and a second phase (e.g., a maintenance phase), wherein (a) the first phase (e.g., induction phase) comprises intravenous administration of only four doses of the anti-TL1 A agent (e.g., anti-TL1 A antibody) at a dose of about 500 mg (e.g., at a dose of 500 mg), wherein (i) the second dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about four weeks after the third dose; and (b) the second phase (e.g., maintenance phase) comprises subcutaneous administration of the anti-TL1 A agent (e.g., anti-TL1 A antibody) every four weeks at a dose of about 450 mg.

[0305] In some aspects, in the second phase (e.g., maintenance phase), the patient (e.g., pediatric patient, e.g., human patient having an age >2 years and <17 years) has a body weight of at least 35 kg and the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered subcutaneously at a dose of about 150 mg (e.g., at a dose of 150 mg).

[0306] In some aspects, the disclosure features a method of treating an IBD (e.g., UC or CD) in a pediatric patient (e.g., a human pediatric patient, e.g., a human patient having an age >2 years and <17 years) having a body weight of at least 35 kg, the method comprising administering to the patient an effective amount of an anti-TL1 A agent (e.g., anti-TL1 A antibody) in a dosing regimen comprising a first phase (e.g., an induction phase) and a second phase (e.g., a maintenance phase), wherein (a) the first phase (e.g., induction phase) comprises intravenous administration of only four doses of the anti-TL1 A agent (e.g., anti-TL1 A antibody) at a dose of about 250 mg (e.g., at a dose of 250 mg), wherein (i) the second dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about four weeks after the third dose; and (b) the second phase (e.g., maintenance phase) comprises subcutaneous administration of the anti-TL1 A agent (e.g., anti-TL1 A antibody) every four weeks at a dose of about 150 mg.PATENT

[0307] Attorney Docket No: 50474-373WO3

[0308] Genentech Docket No: P39855-WO-1

[0309] In some aspects, the anti-TL1 A antibody is afimkibart. In some aspects, (a) the first IV dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered on about Day 1 of Week 0; (b) the second IV dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered on about Day 1 of Week 2; (c) the third IV dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered on about Day 1 of Week 6; (d) the fourth IV dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered on about Day 1 of Week 10; (e) the first SC dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered on about Day 1 of Week 12; and (f) the subsequent SC doses of the anti-TL1 A agent (e.g., anti-TL1 A antibody) are administered on about Day 1 of Weeks 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52. In some aspects, the dosing regimen comprising the first phase and second phase (e.g., induction phase and maintenance phase) has a duration of about 52 weeks (e.g., has a duration of 52 weeks).

[0310] C. Extension Phase

[0311] Any of the methods provided herein may comprise administration of an anti-TL1 A agent (e.g., anti-TL1 A antibody) in an extension phase that follows administration of the anti-TL1 A agent (e.g., anti-TL1 A antibody) in (i) a first phase (e.g., an induction phase) or (ii) a first phase and a second phase (e.g., an induction phase and a maintenance phase). For example, the extension phase may follow (i) a first phase (e.g., induction phase) comprising only IV administration of the anti-TL1 A agent (e.g., anti-TL1 A antibody) or (ii) a first phase (e.g., an induction phase) comprising only IV administration of the anti-TL1 A agent (e.g., anti-TL1 A antibody) and a second phase (e.g., a maintenance phase) comprising SC administration of the anti-TL1 A agent (e.g., anti-TL1 A antibody). The extension phase may comprise administration of one or more doses of the anti-TL1 A agent (e.g., anti-TL1 A antibody).

[0312] The extension phase may be initiated at any appropriate time following the first phase (e.g., induction phase) or the second phase (e.g., maintenance phase). In some aspects, the first dose of the extension phase is administered about four weeks (e.g., four weeks) after administration of the last dose of the second phase (e.g., maintenance phase).

[0313] In some aspects in which the extension phase comprises administration of at least two doses of the anti-TL1 A agent (e.g., anti-TL1 A antibody), the time interval between each individual extension dose may be the same. In other aspects, the time interval between individual extension phase doses is not the same. The individual extension doses can be administered at least daily, at least one day apart, at least 1 week apart, at least 2 weeks apart, at least 3 weeks apart, at least 1 month apart, at least 2 months apart, at least 3 months apart, at least 4 months apart, at least 5 months apart, or at least 6 months apart. In one preferred aspect, the individual extension doses are administered one month apart.

[0314] In some aspects, the extension phase comprises administration of the anti-TL1 A agent (e.g., anti-TL1 A antibody) every four weeks (Q4W).

[0315] In some aspects, the extension phase comprises administration of the anti-TL1 A agent (e.g., anti-TL1 A antibody) every two weeks (Q2W).

[0316] In some aspects, the extension phase comprises (i) at least one interval in which the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered every four weeks (Q4W) and (ii) at least one interval in which the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered every two weeks (Q2W). In somePATENT

[0317] Attorney Docket No: 50474-373WO3

[0318] Genentech Docket No: P39855-WO-1

[0319] aspects, the extension phase closing frequency of a subject is increased from Q4W to Q2W based on observation of disease worsening.

[0320] In one aspect, the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered at a dose of about 450 mg (e.g., at a dose of 450 mg) during the extension phase. Doses in the extension phase can be administered by any means (e.g., may be administered intravenously or subcutaneously). In some aspects, the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered subcutaneously at a dose of 450 mg every four weeks (Q4W).

[0321] In some aspects, in the extension phase, the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered subcutaneously at a dose of about 450 mg (e.g., 450 mg) every four weeks. In some aspects, in the extension phase, the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered subcutaneously at a dose of about 450 mg (e.g., 450 mg) every two weeks. In some aspects, each dose in the extension phase is about 450 mg (e.g., 450 mg), and the extension phase comprises (i) at least one interval in which the anti-TL1 A agent (e.g., anti-TL1 A antibody) is subcutaneously administered every four weeks (Q4W) and (ii) at least one interval in which the anti-TL1 A agent (e.g., anti-TL1 A antibody) is subcutaneously administered every two weeks (Q2W).

[0322] In some aspects, the extension phase comprises administration of 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 doses of the anti-TL1 A agent (e.g., anti-TL1 A antibody).

[0323] In some aspects, the one or more dosing cycles of the extension phase are administered to a patient who experienced disease worsening during the second phase (e.g., maintenance phase). In some aspects, the one or more dosing cycles of the extension phase are administered to a patient who experienced disease worsening during a dosing regimen comprising subcutaneous administration of the anti-TL1 A agent (e.g., anti-TL1 A antibody).

[0324] In some aspects, the one or more dosing cycles of the extension phase are administered to a patient who experienced disease worsening during the first phase (e.g., induction phase). In some aspects, the one or more dosing cycles of the extension phase are administered to a patient who experienced disease worsening during a dosing regimen comprising intravenous administration of the anti-TL1 A agent (e.g., anti-TL1 A antibody).

[0325] D. Corticosteroid Tapering

[0326] In some aspects, the patient was receiving a stable corticosteroid dose (e.g., an oral corticosteroid, e.g., oral prednisone or an equivalent thereof, oral budesonide, or budesonide multi-matrix (MMX)) prior to the treatment, and the patient is tapered off of the corticosteroid during the dosing regimen, e.g., during the first phase (e.g., induction phase), second phase (e.g., maintenance phase), and / or extension phase (e.g., administration of the corticosteroid is discontinued during the first phase (e.g., induction phase), second phase (e.g., maintenance phase), or extension phase). In some embodiments, the patient is tapered off of the corticosteroid during a dosing regimen comprising intravenous administration of the anti-TL1 A agent (e.g., anti-TL1 A antibody). In some aspects, the corticosteroid tapering is initiated between Week 4 and Week 6 of the first phase (e.g., induction phase). In some embodiments, the patient is tapered off of the corticosteroid during a dosing regimen comprisingPATENT

[0327] Attorney Docket No: 50474-373WO3

[0328] Genentech Docket No: P39855-WO-1

[0329] subcutaneous administration of the anti-TL1 A agent (e.g., anti-TL1 A antibody). For example, the dose of the corticosteroid may be tapered by 5 mg per week or 2.5 mg per week.

[0330] In some embodiments, the patient was receiving prednisone or an equivalent thereof administered orally at a dose of more than 10 mg per day in the induction phase, and the tapering comprises (i) tapering the dose by 5 mg per week until the patient is receiving a dose of 10 mg per day; and then (ii) tapering the dose by 2.5 mg / week until a dose of 0 mg per week is reached (e.g., tapering the dose by 2.5 mg per week for three weeks).

[0331] In some embodiments, the patient was receiving prednisone or an equivalent thereof administered orally at a dose of 10 mg or less per day in the induction phase, and the tapering comprises tapering the dose by 2.5 mg / week until a dose of 0 mg per week is reached (e.g., comprises tapering the dose by 2.5 mg per week for up to three weeks).

[0332] In some embodiments, the patient was receiving budesonide or budesonide MMX administered orally at a dose of 9 mg or less per day in the induction phase, and the tapering comprises the steps of (i) administering 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 third day for two weeks; and (iii) discontinuing administration of the corticosteroid.

[0333] In some embodiments, the patient was receiving budesonide administered orally at a dose of 6 mg or less per day in the induction phase, and the tapering comprises tapering the dose to 3 mg / day for two weeks, and then discontinuing administration of the budesonide.

[0334] E. Response to Treatment

[0335] Clinical Response

[0336] Following the dosing regimen of the anti-TL1 A agent (e.g., anti-TL1 A antibody) (e.g., following the first phase (e.g., induction dosing regimen) and / or the second phase (e.g., maintenance dosing regimen)), the patient may experience an improvement in signs and symptoms of IBD characterized by a clinical response.

[0337] In some aspects, the IBD is UC, and a clinical response is defined as a decrease in modified Mayo Score (mMS) of at least 2 points and 30% from baseline and either a decrease in rectal bleeding subscore (RBS) > 1 or an RBS of 0 or 1 . In some aspects, the IBD is CD, and a clinical response is defined as a decrease in PCDAI score of at least 12.5.

[0338] In some aspects, in a population of patients treated according to any one of the methods provided herein, the treating results in an increase in the proportion of patients who have achieved a clinical response at the end of the first phase (e.g., induction phase) as compared to a reference population. For example, in some aspects, the first phase (e.g., induction phase) has a duration of about 12 weeks, and the treating results in an increase in the proportion of patients who have achieved a clinical response at Week 12. For example, in some aspects, 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% of patients) in the population of patients have achieved a clinical response at Week 12. In some aspects, the proportion of patients in the population of patients who have achieved a clinical response at Week 12 is at least 5%, 10%, 15%, 20%,PATENT

[0339] Attorney Docket No: 50474-373WO3

[0340] Genentech Docket No: P39855-WO-1

[0341] 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 80%, 95%, or 99% greater than the proportion of patients who have achieved a clinical response at Week 12 in the reference population. In some aspects, in a population of patients treated according to any one of the methods comprising a second phase (e.g., maintenance phase) provided herein, the treating results in an increase in the proportion of patients who have achieved a clinical response at the end of the second phase (e.g., maintenance phase) as compared to a reference population. For example, in some aspects, the dosing regimen has a duration of about 52 weeks, and the treating results in an increase in the proportion of patients who have achieved a clinical response at Week 52. For example, in some aspects, 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% of patients) in the population of patients have achieved a clinical response at Week 52. In some aspects, the proportion of patients in the population of patients who have achieved 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 who have achieved a clinical response at Week 52 in the reference population.

[0342] In any of the methods provided herein, the reference population may be any population that serves as an appropriate control. For example, in some aspects, the reference population is a population of subjects having an IBD (e.g., UC (e.g., moderately or severely active UC) or CD (e.g., moderately or severely active CD)) who have not been treated with an anti-TL1 A agent (e.g., anti-TL1 A antibody).

[0343] Endoscopic Response

[0344] Following the dosing regimen of the anti-TL1 A agent (e.g., anti-TL1 A antibody) (e.g., following the first phase (e.g., induction dosing regimen) and / or the second phase (e.g., maintenance dosing regimen)), the patient may experience an improvement in signs and symptoms of IBD characterized by an endoscopic response.

[0345] In some aspects, the IBD is UC, and an endoscopic response is defined as a Mayo endoscopy subscore 0 or 1 .

[0346] In some aspects, the IBD is CD, and an endoscopic response is defined as decrease in Simple Endoscopic Score for Crohn’s disease (SES-CD) that is at least 50% lower than a baseline SES-CD.

[0347] In some aspects, in a population of patients treated according to any one of the methods provided herein, the treating results in an increase in the proportion of patients who have achieved an endoscopic response at the end of the first phase (e.g., induction phase) as compared to a reference population. For example, in some aspects, the first phase (e.g., induction phase) has a duration of about 12 weeks, and the treating results in an increase in the proportion of patients who have achieved an endoscopic response at Week 12. For example, in some aspects, 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% of patients) in the population of patients have achieved an endoscopic response at Week 12. In some aspects, the proportion of patients in the population of patients who have achieved an endoscopic response at Week 12 is at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%,PATENT

[0348] Attorney Docket No: 50474-373WO3

[0349] Genentech Docket No: P39855-WO-1

[0350] 85%, 80%, 95%, or 99% greater than the proportion of patients who have achieved an endoscopic response at Week 12 in the reference population. In some aspects, in a population of patients treated according to any one of the methods comprising a second phase (e.g., maintenance phase) provided herein, the treating results in an increase in the proportion of patients who have achieved an endoscopic response at the end of the second phase (e.g., maintenance phase) as compared to a reference population. For example, in some aspects, the dosing regimen has a duration of about 52 weeks, and the treating results in an increase in the proportion of patients who have achieved an endoscopic response at Week 52. For example, in some aspects, 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% of patients) in the population of patients have achieved an endoscopic response at Week 52. In some aspects, the proportion of patients in the population of patients who have achieved 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 who have achieved an endoscopic response at Week 52 in the reference population.

[0351] In any of the methods provided herein, the reference population may be any population that serves as an appropriate control. For example, in some aspects, the reference population is a population of subjects having an IBD (e.g., UC (e.g., moderately or severely active UC) or CD (e.g., moderately or severely active CD)) who have not been treated with an anti-TL1 A agent (e.g., anti-TL1 A antibody).

[0352] Clinical Remission

[0353] Following the first dosing regimen (e.g., induction dosing regimen) and / or the second dosing regimen (e.g., maintenance dosing regimen), the patient may experience an improvement in signs and symptoms of IBD characterized by a clinical remission.

[0354] In some aspects, in a population of patients treated according to any one of the methods provided herein, the treating results in an increase in the proportion of patients who have achieved clinical remission at the end of the first phase (e.g., induction phase) as compared to a reference population. For example, in some aspects, the first phase (e.g., induction phase) has a duration of about 12 weeks, and the treating results in an increase in the proportion of patients who have achieved clinical remission at Week 12. For example, in some aspects, 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% of patients) in the population of patients have achieved clinical remission at Week 12. In some aspects, the proportion of patients in the population of patients who have achieved 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 who have achieved clinical remission at Week 12 in the reference population.

[0355] In some aspects, in a population of patients treated according to any one of the methods comprising a second phase (e.g., maintenance phase) provided herein, the treating results in an increase in the proportion of patients who have achieved clinical remission at the end of the second phase (e.g.,PATENT

[0356] Attorney Docket No: 50474-373WO3

[0357] Genentech Docket No: P39855-WO-1

[0358] maintenance phase) as compared to a reference population. For example, in some aspects, the dosing regimen has a duration of about 52 weeks, and the treating results in an increase in the proportion of patients who have achieved clinical remission at Week 52. For example, in some aspects, 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% of patients) in the population of patients have achieved clinical remission at Week 52. In some aspects, the proportion of patients in the population of patients who have achieved 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 who have achieved clinical remission at Week 52 in the reference population.

[0359] In some aspects, in a population of patients treated according to any one of the methods comprising a maintenance phase provided herein, the treating results in an increase in the proportion of patients who experience maintenance of remission throughout the second phase (e.g., maintenance phase) as compared to a reference population. For example, in some aspects, the first phase (e.g., induction phase) has a duration of about 12 weeks, the entire dosing regimen has a duration of about 52 weeks, and the treating results in an increase in the proportion of patients who are experiencing clinical remission at Week 12 and at Week 52.

[0360] In some aspects, the IBD is UC, and clinical remission is defined as a modified Mayo Score (mMS) <2 with rectal bleeding score (RBS) of 0, stool frequency subscore (SFS) = 0 or 1 , and endoscopic subscore (ES) = 0 or 1 . The mMS is evaluated as a composite based on three assessments, described in further detail below: stool frequency subscore (SFS), rectal bleeding subscore (RFS), and endoscopic subscore (ES). Each of these assessments has scoring that ranges from 0 to 3, with higher values indicating greater severity. mMS is calculated as the sum of SFS, RBS, and ES, with range 0-9.

[0361] SFS and RBS are calculated as an average over 7 days prior to the relevant timepoint.

[0362] SFS is quantified as follows:

[0363] With normal defined at baseline, with respect to each individual participant:

[0364] 0 = Normal number of stools for this patient.

[0365] 1 = 1-2 more stools than normal.

[0366] 2 = 3-4 more stools than normal.

[0367] 3 = 5 or more stools than normal.

[0368] RBS is quantified as follows:

[0369] Representing the worst rectal bleeding observed by the participant that day:

[0370] 0 = No blood seen or no bowel movement.

[0371] 1 = Stool with streaks of blood.

[0372] 2 = Stool with more than streaks of blood.

[0373] 3 = Blood alone passed.PATENT

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[0376] ES is quantified as follows:

[0377] 0 = Normal appearance of mucosa.

[0378] 1 = Mild disease (erythema, decreased vascular pattern, no friability).

[0379] 2 = Moderate disease (marked erythema, absent vascular pattern, friability, erosions).

[0380] 3 = Severe disease (spontaneous bleeding, ulceration).

[0381] In other aspects, the term “clinical remission” is based on 12-point total Mayo score: total Mayo score < 2 with no individual subscore >1. In some aspects, Per Adapted (Modified) Mayo score is defined as endoscopic subscore = 0 or 1 , >= 1 -point decrease from baseline to achieve a stool frequency subscore = 0 or 1 , and rectal bleeding subscore = 0. In some aspects, Per Adapted (Modified) Mayo score is defined as endoscopic subscore = 0 or 1 , a stool frequency subscore = 0 or 1 with no increase from baseline, and rectal bleeding subscore = 0.

[0382] In some aspects, the IBD is UC, and clinical remission is defined as a pediatric Crohn’s disease activity index (PCDAI) of less than 10.

[0383] Endoscopic Remission

[0384] Following the first dosing regimen (e.g., induction dosing regimen) and / or the second dosing regimen (e.g., maintenance dosing regimen), the patient may experience an improvement in signs and symptoms of IBD characterized by an endoscopic remission. The term “endoscopic remission” refers to a Mayo endoscopy subscore of 0. In some aspects, the patient experiences endoscopic remission at or before the end of the first phase (e.g., induction phase), e.g., at or before Week 12 of treatment. In some aspects, in a population of patients treated according to any one of the methods provided herein, the treating results in an increase in the proportion of patients who have achieved endoscopic remission at the end of the first phase (e.g., induction phase) as compared to a reference population. In some aspects, the patient experiences endoscopic remission at or before the end of the second phase (e.g., maintenance phase), e.g., at or before Week 52 of treatment. In some aspects, in a population of patients treated according to any one of the methods provided herein, the treating results in an increase in the proportion of patients who have achieved endoscopic remission at the end of the second phase (e.g., maintenance phase) as compared to a reference population.

[0385] Deep Remission

[0386] Following the first dosing regimen (e.g., induction dosing regimen) and / or the second dosing regimen (e.g., maintenance dosing regimen), the patient may experience an improvement in signs and symptoms of IBD characterized by a deep remission.

[0387] In some aspects, the IBD is UC, and the term “deep remission” refers to a total Mayo score of 2 points or lower, with no individual subscore exceeding 1 point and a 0 on both endoscopic and rectal bleeding subscore.

[0388] In some aspects, in a population of patients treated according to any one of the methods provided herein, the treating results in an increase in the proportion of patients who have achieved deepPATENT

[0389] Attorney Docket No: 50474-373WO3

[0390] Genentech Docket No: P39855-WO-1

[0391] remission at the end of the first phase (e.g., induction phase) as compared to a reference population. In some aspects, the patient experiences deep remission at or before the end of the second phase (e.g., maintenance phase), e.g., at or before Week 52 of treatment. In some aspects, in a population of patients treated according to any one of the methods provided herein, the treating results in an increase in the proportion of patients who have achieved deep remission at the end of the second phase (e.g., maintenance phase) as compared to a reference population.

[0392] Symptomatic Remission

[0393] Following the first dosing regimen (e.g., induction dosing regimen) and / or the second dosing regimen (e.g., maintenance dosing regimen), the patient may experience an improvement in signs and symptoms of IBD characterized by a symptomatic remission.

[0394] In some aspects, the IBD is UC, and the term “symptomatic remission” refers to a total Mayo score of 2 points or lower, with no individual subscore exceeding 1 point, and both rectal bleeding and stool frequency subscores of 0.

[0395] In some aspects, in a population of patients treated according to any one of the methods provided herein, the treating results in an increase in the proportion of patients who have achieved symptomatic remission at the end of the first phase (e.g., induction phase) as compared to a reference population. In some aspects, the patient experiences symptomatic remission at or before the end of the second phase (e.g., maintenance phase), e.g., at or before Week 52 of treatment. In some aspects, in a population of patients treated according to any one of the methods provided herein, the treating results in an increase in the proportion of patients who have achieved symptomatic remission at the end of the second phase (e.g., maintenance phase) as compared to a reference population.

[0396] Endoscopic Improvement

[0397] Following the first dosing regimen (e.g., induction dosing regimen) and / or the second dosing regimen (e.g., maintenance dosing regimen), the patient may experience an improvement in signs and symptoms of IBD characterized by an endoscopic improvement.

[0398] In some aspects, the IBD is UC, and the term “endoscopic improvement” ("El") refers to a decrease of >1 point in Mayo endoscopy subscore or an absolute endoscopy score of <1. In some aspects, endoscopic improvement is defined as an endoscopic subscore of 0 or 1 .

[0399] In some aspects, the patient experiences endoscopic improvement at or before the end of the first phase (e.g., induction phase), e.g., at or before Week 12 of treatment. In some aspects, in a population of patients treated according to any one of the methods provided herein, the treating results in an increase in the proportion of patients who have achieved endoscopic improvement at the end of the first phase (e.g., induction phase) as compared to a reference population. For example, in some aspects, the first phase (e.g., induction phase) has a duration of about 12 weeks, and the treating results in an increase in the proportion of patients who have achieved endoscopic improvement at Week 12. 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-PATENT

[0400] Attorney Docket No: 50474-373WO3

[0401] Genentech Docket No: P39855-WO-1

[0402] 60%, 60-70%, 70-80%, 80-90%, or 90-100% of patients) in the population of patients have achieved endoscopic improvement at Week 12.

[0403] In some aspects, the proportion of patients in the population of patients who have achieved 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 who have achieved endoscopic improvement at Week 12 in the reference population.

[0404] In some aspects, the patient experiences endoscopic improvement at or before the end of the second phase (e.g., maintenance phase), e.g., at or before Week 52 of treatment. In some aspects, in a population of patients treated according to any one of the methods provided herein, the treating results in an increase in the proportion of patients who have achieved endoscopic improvement at the end of the second phase (e.g., maintenance phase) as 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 patients) in the population of patients have achieved endoscopic improvement at Week 52.

[0405] In some aspects, the proportion of patients in the population of patients who have achieved 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 who have achieved endoscopic improvement at Week 52 in the reference population.

[0406] Improvement in Signs and Symptoms of IBD

[0407] Following the first dosing regimen (e.g., induction dosing regimen) and / or the second dosing regimen (e.g., maintenance dosing regimen), the patient may experience an improvement in signs and symptoms of IBD that are maintained while the patient receives the second dosing regimen (e.g., maintenance dosing regimen).

[0408] In some aspects of the disclosure, the first dosing regimen (e.g., induction dosing regimen) and / or the second dosing regimen (e.g., maintenance dosing regimen) with the anti-TL1 A agent (e.g., anti-TL1 A antibody) effectively improves signs and symptoms of IBD by at least 12 weeks after starting of treatment with the anti-TL1 A agent (e.g., anti-TL1 A antibody). These improvement in signs and symptoms of IBD may be characterized by an improvement in the Mayo endoscopic subscore. The reduction of the patient’s Mayo endoscopic subscore may be by at least 1 , 2, or 3 or more integers.

[0409] The improvement in signs and symptoms of IBD may be characterized by the patient having a Mayo endoscopic subscore of 0 or 1 , 2, or 3. The improvement in signs and symptoms of IBD may be characterized by the patient having a total Mayo score of 0, 1 , 2, or 3. The improvement in signs and symptoms of IBD may be characterized by the patient having a Robarts Histopathology Index (RHI) of less than 5. The improvement in signs and symptoms of IBD may be characterized by the patient having a Geboes Index of less than 3.2.

[0410] The improvement in signs and symptoms of IBD may be maintained during the second dosing regimen (e.g., maintenance dosing regimen) for at least 2, 3, 4, 6, or 12 months.PATENT

[0411] Attorney Docket No: 50474-373WO3

[0412] Genentech Docket No: P39855-WO-1

[0413] F. Prior Treatment

[0414] In some aspects, the patient has previously been treated with a therapy for IBD (e.g., a therapy for UC) and has experienced inadequate response to the therapy, loss of response to the therapy, and / or intolerance of the therapy.

[0415] In some aspects, the therapy was a conventional therapy for UC, e.g., comprised administration of a steroid, an immunomodulator, or an oral aminosalicylate (e.g., the patient has experienced inadequate response to, loss of response to, and / or intolerance of a steroid, an immunomodulator, and / or an oral aminosalicylate).

[0416] In some aspects, the therapy was an advanced therapy for UC, e.g., comprised administration of an anti-tumor necrosis factor (TNF) agent, an anti-integrin agent, an anti-IL12 / IL23 agent, a Janus kinase (JAK) inhibitor, or a sphingosine-1 -phosphate (S1 P) inhibitor (e.g., the patient has experienced inadequate response to, loss of response to, and / or intolerance of an anti-TNF agent, an anti-integrin agent, an anti-IL12 / IL23 agent, a JAK inhibitor, or a S1 P inhibitor). Thus, in some aspects, the patient had received prior advanced therapy at baseline (e.g., before administration of the first dose of the induction phase). In other aspects, the patient had not received prior advanced therapy at baseline.

[0417] In some aspects, the patient was receiving a corticosteroid therapy at baseline (e.g., before administration of the first dose of the induction phase). In other aspects, the patient was not receiving corticosteroid therapy at baseline.

[0418] G. Inflammatory Bowel Diseases

[0419] Ulcerative colitis

[0420] In some aspects the IBD is ulcerative colitis (UC).

[0421] In some aspects, the UC is moderately to severely active UC. In some aspects, the moderately to severely active UC is UC having a modified Mayo score (mMS) of between 5 points and 9 points. In some aspects, the moderately to severely active UC is UC having a mMS of between 5 points and 9 points and a Mayo endoscopic score (ES) of 2 or 3. Thus, in some aspects, a patient to be treated according to the methods provided herein has UC with a mMS of 5 to 6 or has UC with a mMS of 7 to 9.

[0422] In some aspects, the disclosure features a method of treating UC (e.g., moderately to severely active UC) in a pediatric patient (e.g., a human pediatric patient, e.g., a human patient having an age >2 years and <17 years) having a body weight of at least 10 kg and less than 35 kg, the method comprising administering to the patient an effective amount of an anti-TL1 A agent (e.g., anti-TL1 A antibody) in a dosing regimen comprising a first phase (e.g., an induction phase) and a second phase (e.g., a maintenance phase), wherein (a) the first phase (e.g., induction phase) comprises intravenous administration of only four doses of the anti-TL1 A agent (e.g., anti-TL1 A antibody) at a dose of about 16 mg / kg (e.g., at a dose of 16 mg / kg), wherein the dose does not exceed 500 mg, wherein (i) the second dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about four weeks after the third dose; and (b) the second phase (e.g., maintenance phase)PATENT

[0423] Attorney Docket No: 50474-373WO3

[0424] Genentech Docket No: P39855-WO-1

[0425] comprises subcutaneous administration of the anti-TL1 A agent (e.g., anti-TL1 A antibody) every four weeks at a dose of about 150 mg.

[0426] In some aspects, the disclosure features a method of treating UC (e.g., moderately to severely active UC) in a pediatric patient (e.g., a human pediatric patient, e.g., a human patient having an age >2 years and <17 years) having a body weight of at least 10 kg and less than 35 kg, the method comprising administering to the patient an effective amount of an anti-TL1 A agent (e.g., anti-TL1 A antibody) in a dosing regimen comprising a first phase (e.g., an induction phase) and a second phase (e.g., a maintenance phase), wherein (a) the first phase (e.g., induction phase) comprises intravenous administration of only four doses of the anti-TL1 A agent (e.g., anti-TL1 A antibody) at a dose of about 8 mg / kg (e.g., at a dose of 8 mg / kg), wherein the dose does not exceed 250 mg, wherein (i) the second dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about four weeks after the third dose; and (b) the second phase (e.g., maintenance phase) comprises subcutaneous administration of the anti-TL1 A agent (e.g., anti-TL1 A antibody) every four weeks at a dose of about 50 mg.

[0427] In some aspects, the disclosure features a method of treating UC (e.g., moderately to severely active UC) in a pediatric patient (e.g., a human pediatric patient, e.g., a human patient having an age >2 years and <17 years) having a body weight of at least 35 kg, the method comprising administering to the patient an effective amount of an anti-TL1 A agent (e.g., anti-TL1 A antibody) in a dosing regimen comprising a first phase (e.g., an induction phase) and a second phase (e.g., a maintenance phase), wherein (a) the first phase (e.g., induction phase) comprises intravenous administration of only four doses of the anti-TL1 A agent (e.g., anti-TL1 A antibody) at a dose of about 500 mg (e.g., at a dose of 500 mg), wherein (i) the second dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about four weeks after the third dose; and (b) the second phase (e.g., maintenance phase) comprises subcutaneous administration of the anti-TL1 A agent (e.g., anti-TL1 A antibody) every four weeks at a dose of about 450 mg.

[0428] In some aspects, the disclosure features a method of treating UC (e.g., moderately to severely active UC) in a pediatric patient (e.g., a human pediatric patient, e.g., a human patient having an age >2 years and <17 years) having a body weight of at least 35 kg, the method comprising administering to the patient an effective amount of an anti-TL1 A agent (e.g., anti-TL1 A antibody) in a dosing regimen comprising a first phase (e.g., an induction phase) and a second phase (e.g., a maintenance phase), wherein (a) the first phase (e.g., induction phase) comprises intravenous administration of only four doses of the anti-TL1 A agent (e.g., anti-TL1 A antibody) at a dose of about 250 mg (e.g., at a dose of 250 mg), wherein (i) the second dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about four weeks after the third dose; and (b) the second phasePATENT

[0429] Attorney Docket No: 50474-373WO3

[0430] Genentech Docket No: P39855-WO-1

[0431] (e.g., maintenance phase) comprises subcutaneous administration of the anti-TL1 A agent (e.g., anti-TL1 A antibody) every four weeks at a dose of about 150 mg.

[0432] In some aspects, the anti-TL1 A antibody comprises the following CDRs: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8. In some aspects, the anti-TL1 A antibody is afimkibart.

[0433] Crohn’s disease

[0434] In some aspects, the IBD is Crohn’s disease (CD).

[0435] In some aspects, the CD is moderately to severely active CD. In some aspects, a patient having moderately to severely active CD (a) has a Simple Endoscopic Score for Crohn’s Disease (SES-CD) of equal to or greater than 6; or (b) has isolated ileal disease only, and has an SES-CD of equal to or greater than 4. In some aspects, a patient having moderately to severely active CD (a) has a SES-CD of equal to or greater than 6 or (b) has isolated ileal disease only, and has an SES-CD of equal to or greater than 4, and has a pediatric Crohn’s disease activity index (CDAI) that is at least 30. Thus, in some aspects, a patient to be treated according to the methods provided herein has CD with a PCDAI score of > 30 and a SES-CD of > 6 (or > 4 for isolated ileal disease only).

[0436] In some aspects, the disclosure features a method of treating CD (e.g., moderately to severely active CD) in a pediatric patient (e.g., a human pediatric patient, e.g., a human patient having an age >2 years and <17 years) having a body weight of at least 10 kg and less than 35 kg, the method comprising administering to the patient an effective amount of an anti-TL1 A agent (e.g., anti-TL1 A antibody) in a dosing regimen comprising a first phase (e.g., an induction phase) and a second phase (e.g., a maintenance phase), wherein (a) the first phase (e.g., induction phase) comprises intravenous administration of only four doses of the anti-TL1 A agent (e.g., anti-TL1 A antibody) at a dose of about 16 mg / kg (e.g., at a dose of 16 mg / kg), wherein the dose does not exceed 500 mg, wherein (i) the second dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about four weeks after the third dose; and (b) the second phase (e.g., maintenance phase) comprises subcutaneous administration of the anti-TL1 A agent (e.g., anti-TL1 A antibody) every four weeks at a dose of about 150 mg.

[0437] In some aspects, the disclosure features a method of treating CD (e.g., moderately to severely active CD) in a pediatric patient (e.g., a human pediatric patient, e.g., a human patient having an age >2 years and <17 years) having a body weight of at least 10 kg and less than 35 kg, the method comprising administering to the patient an effective amount of an anti-TL1 A agent (e.g., anti-TL1 A antibody) in a dosing regimen comprising a first phase (e.g., an induction phase) and a second phase (e.g., a maintenance phase), wherein (a) the first phase (e.g., induction phase) comprises intravenous administration of only four doses of the anti-TL1 A agent (e.g., anti-TL1 A antibody) at a dose of about 8PATENT

[0438] Attorney Docket No: 50474-373WO3

[0439] Genentech Docket No: P39855-WO-1

[0440] mg / kg (e.g., at a dose of 8 mg / kg), wherein the dose does not exceed 250 mg, wherein (i) the second dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about four weeks after the third dose; and (b) the second phase (e.g., maintenance phase) comprises subcutaneous administration of the anti-TL1 A agent (e.g., anti-TL1 A antibody) every four weeks at a dose of about 50 mg.

[0441] In some aspects, the disclosure features a method of treating CD (e.g., moderately to severely active CD) in a pediatric patient (e.g., a human pediatric patient, e.g., a human patient having an age >2 years and <17 years) having a body weight of at least 35 kg, the method comprising administering to the patient an effective amount of an anti-TL1 A agent (e.g., anti-TL1 A antibody) in a dosing regimen comprising a first phase (e.g., an induction phase) and a second phase (e.g., a maintenance phase), wherein (a) the first phase (e.g., induction phase) comprises intravenous administration of only four doses of the anti-TL1 A agent (e.g., anti-TL1 A antibody) at a dose of about 500 mg (e.g., at a dose of 500 mg), wherein (i) the second dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about four weeks after the third dose; and (b) the second phase (e.g., maintenance phase) comprises subcutaneous administration of the anti-TL1 A agent (e.g., anti-TL1 A antibody) every four weeks at a dose of about 450 mg.

[0442] In some aspects, the disclosure features a method of treating CD (e.g., moderately to severely active CD) in a pediatric patient (e.g., a human pediatric patient, e.g., a human patient having an age >2 years and <17 years) having a body weight of at least 35 kg, the method comprising administering to the patient an effective amount of an anti-TL1 A agent (e.g., anti-TL1 A antibody) in a dosing regimen comprising a first phase (e.g., an induction phase) and a second phase (e.g., a maintenance phase), wherein (a) the first phase (e.g., induction phase) comprises intravenous administration of only four doses of the anti-TL1 A agent (e.g., anti-TL1 A antibody) at a dose of about 250 mg (e.g., at a dose of 250 mg), wherein (i) the second dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about four weeks after the second dose; and (iii) the fourth dose of the anti-TL1 A agent (e.g., anti-TL1 A antibody) is administered about four weeks after the third dose; and (b) the second phase (e.g., maintenance phase) comprises subcutaneous administration of the anti-TL1 A agent (e.g., anti-TL1 A antibody) every four weeks at a dose of about 150 mg.

[0443] In some aspects, the anti-TL1 A antibody comprises the following CDRs: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8. In some aspects, the anti-TL1 A antibody is afimkibart.PATENT

[0444] Attorney Docket No: 50474-373WO3

[0445] Genentech Docket No: P39855-WO-1

[0446] H. Pediatric Patient is a TNFSF15 Haplotype B Non-Carrier

[0447] In some aspects, any of the methods, uses, or compositions for use provided herein comprise determining the TNFSF15 haplotype of a pediatric patient (e.g., a human pediatric patient, e.g., a human patient having an age >2 years and <17 years), e.g., comprise determining whether a patient is (a) a TNFSF15 haplotype B carrier or (b) a TNFSF15 haplotype B non-carrier. The methods, uses, or compositions for use may further include making a treatment decision on the basis of the pediatric patient’s TNFSF15 haplotype. In some aspects, a pediatric patient identified for treatment with a method provided herein is a haplotype B non-carrier for TNFSF15 (e.g., has been determined to be a haplotype B non-carrier for TNFSF15).

[0448] Haplotype B is defined as a TNFSF15 gene region that has the nucleotides T / C / A / T / C at position 15,524; position 9,706; position -358; position -638; and position -12,506, respectively, based on the reference sequence GenBank NM_005118.2, wherein the first nucleotide of the exon 1 start site is designated as position 1 (haplotype positions 26 / 31 / 35 / 36 / 41 , respectively, as provided in Yamazaki et al., Human Molecular Genetics, 14(22): 3499-3506, 2005), in the TNFSF15 gene region, which encodes the TL1 A gene (Table 1). A subject is identified as haplotype B if the subject is heterozygous or homozygous for haplotype B, i.e., one or both copies of the gene region are haplotype B (i.e., one or both of the TNFSF15 gene regions have the nucleotides T / C / A / T / C at haplotype positions 15,524; 9,706; -358; -638; and -12,506 (26 / 31 / 35 / 36 / 41).

[0449] Table 1. TNFSF15 gene region SNPs of interest

[0450]

[0451] Haplotype positions 15,524; 9,706; -358; -638; and -12,506 (26, 31, 35, 36 and 41) correspond to the sites of the SNPs rs3810936, rs6478108, rs6478109, rs7848647, and rs7869487, respectively, as identified in the NIH NCBI dbSNP database (see Table 1). Haplotype B comprises the reference nucleotide at each of these positions: thus, a haplotype B TNFSF15 gene region can be identified by the absence of each of SNPs rs3810936, rs6478108, rs6478109, rs7848647, and rs7869487 (i.e., the presence of the reference allele at each of these sites).PATENT

[0452] Attorney Docket No: 50474-373WO3

[0453] Genentech Docket No: P39855-WO-1

[0454] Haplotype B non-carrier subjects are defined as subjects that do not carry a haplotype B TNFSF15 gene region. For example, a haplotype B non-carrier subject may be homozygous for a nonhaplotype B allele, e.g., haplotype A (e.g., may have the nucleotides C / T / G / C / T at haplotype positions 26 / 31 / 35 / 36 / 41). See, e.g., Michelsen et al., PLoS One, 4(3): e4719, 2009).

[0455] III. Anti-TL1 A Agents

[0456] A. Anti-TL1 A antibodies

[0457] In some aspects, the methods of the present disclosure include the administration of an anti-TL1 A agent that is an antibody (e.g., an anti-TL1 A antibody, e.g., an anti-TL1 A antagonist antibody). Exemplary anti-TL1 A antibodies of the disclosure are set forth in Table 2.

[0458] Table 2. Sequences of Exemplary Antibodies of the Disclosure

[0459]

[0460] PATENT

[0461] Attorney Docket No: 50474-373WO3

[0462] Genentech Docket No: P39855-WO-1

[0463]

[0464] In some aspects of the disclosure, the anti-TL1 A antibody comprises a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3, a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4, a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5, a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8. In some aspects, the anti-TL1 A antibody comprises one, two, three, four, five, six, seven, or all eight of the framework region sequences shown in SEQ ID NOs: 13-20.

[0465] In some aspects of the disclosure, the anti-TL1 A antibody comprises a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 12, a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4, a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5, a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8. In some aspects, the anti-TL1 A antibody comprises one, two, three, four, five, six, seven, or all eight of the framework region sequences shown in SEQ ID NOs: 14-21.

[0466] In some aspects of the disclosure, the anti-TL1 A 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.,PATENT

[0467] Attorney Docket No: 50474-373WO3

[0468] Genentech Docket No: P39855-WO-1

[0469] having at least 96%, 97%, 98%, or 99% identity to SEQ ID NO: 1) and / or comprises a light chain variable (VL) domain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 2 (e.g., having at least 96%, 97%, 98%, or 99% identity to SEQ ID NO: 2).

[0470] In some aspects of the disclosure, the anti-TL1 A antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 1 and / or comprises a VL domain comprising the amino acid sequence of SEQ ID NO: 2.

[0471] In some aspects of the disclosure, the anti-TL1 A antibody comprises a VH having the sequence shown in SEQ ID NO: 1 and a VL having the sequence shown in SEQ ID NO: 2.

[0472] In some aspects of the disclosure, the anti-TL1 A antibody comprises (a) a heavy chain comprising an amino acid sequence having at least 95% sequence identity to 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 to SEQ ID NO: 9 or SEQ ID NO: 11); and / or (b) a light chain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 10 (e.g., having at least 96%, 97%, 98%, or 99% identity to SEQ ID NO: 10).

[0473] In some aspects, the anti-TL1 A antibody comprises (a) a heavy chain comprising the amino acid sequence of SEQ ID NO: 9; and / or (b) a light chain comprising the amino acid sequence of SEQ ID NO: 10. In some aspects, the anti-TL1 A antibody comprises (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.

[0474] In some aspects of the disclosure, the anti-TL1 A antibody comprises a heavy chain having the sequence shown in SEQ ID NO: 11. In some embodiments, the anti-TL1 A 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 the C-terminal lysine (K). In some embodiments, the heavy chain has the sequence shown in SEQ ID NO: 9. In some embodiments, the anti-TL1 A 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.

[0475] In some aspects of the disclosure, the anti-TL1 A antibody is afimkibart (also known as RO7790121, RVT-3101, or PF-06480605).

[0476] Further exemplary anti-TL1 A antibodies are set forth in Table 3 and below.

[0477] Table 3. Further Sequences of Exemplary Antibodies of the Disclosure

[0478]

[0479] PATENT

[0480] Attorney Docket No: 50474-373WO3

[0481] Genentech Docket No: P39855-WO-1

[0482]

[0483] PATENT

[0484] Attorney Docket No: 50474-373WO3

[0485] Genentech Docket No: P39855-WO-1

[0486]

[0487] PATENT

[0488] Attorney Docket No: 50474-373WO3

[0489] Genentech Docket No: P39855-WO-1

[0490]

[0491] PATENT

[0492] Attorney Docket No: 50474-373WO3

[0493] Genentech Docket No: P39855-WO-1

[0494]

[0495] PATENT

[0496] Attorney Docket No: 50474-373WO3

[0497] Genentech Docket No: P39855-WO-1

[0498]

[0499] In some aspects of the disclosure, the anti-TL1 A antibody comprises a VH encoded by the nucleic acid sequence of the insert of the vector deposited as 1 D1 1 .31 VH having ATCC accession number PTA-120639 and a VL encoded by the nucleic acid sequence of the insert of the vector deposited as 1 D1 1.31 VL having ATCC accession number PTA-120640.

[0500] In some aspects of the disclosure, the anti-TL1 A antibody competes for binding with an anti-TL1 A 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.

[0501] In some aspects of the disclosure, the anti-TL1 A antibody competes for binding with an antibody comprising a VH encoded by the nucleic acid sequence of the insert of the vector deposited as 1 D1 1 .31 VH having ATCC accession number PTA-120639 and a VL encoded by the nucleic acid sequence of the insert of the vector deposited as 1 D1 1 .31 VL having ATCC accession number PTA-120640.

[0502] In some aspects of the disclosure, the anti-TL1 A antibody comprises sequence pairs 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.

[0503] In some aspects of the disclosure, the anti-TL1 A antibody comprises a CDR-H1 having the sequence shown in SEQ ID NO: 47, a CDR-H2 having the sequence shown in SEQ ID NO: 49, a CDR-H3 having the sequence shown in SEQ ID NO: 51 , a CDR-L1 having the sequence shown in SEQ ID NO: 56, a CDR-L2 having the sequence shown in SEQ ID NO: 58, and a CDR-L3 having the sequence shown in SEQ ID NO: 60.

[0504] In some aspects of the disclosure, the anti-TL1 A antibody comprises heavy chain framework regions as shown in SEQ ID NOs: 46, 48, 50, and 52 and / or comprises light chain framework regions as shown in SEQ ID NOs: 55, 57, 59, and 61 .

[0505] In some aspects of the disclosure, the anti-TL1 A 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.PATENT

[0506] Attorney Docket No: 50474-373WO3

[0507] Genentech Docket No: P39855-WO-1

[0508] In some aspects of the disclosure, the anti-TL1 A antibody comprises a heavy chain tail sequence as provided in SEQ ID NO: 53. In some aspects of the disclosure, the anti-TL1 A antibody comprises a light chain tail sequence as provided in SEQ ID NO: 62.

[0509] In some aspects of the disclosure, the anti-TL1 A antibody comprises a heavy chain having the sequence shown in SEQ ID NO: 45 and / or a light chain having the sequence shown in SEQ ID NO: 54. In some aspects of the disclosure, the anti-TL1 A antibody comprises a heavy chain having the sequence shown in SEQ ID NO: 45 and a light chain having the sequence shown in SEQ ID NO: 54.

[0510] In some aspects of the disclosure, the anti-TL1 A antibody is tulisokibart (Merck).

[0511] In some aspects, the antibody used in any of the methods, compositions, uses, and compositions for use provided herein is an anti-TL1 A antibody provided in Table 2A of U.S. Patent No. 11 ,136,386, which is incorporated herein by reference in its entirety.

[0512] In some aspects of any of the methods, compositions, uses, and compositions for use provided herein, the anti-TL1 A antibody is an anti-TL1 A 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.

[0513] 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-TL1 A antibody comprises the CDR sequences of the 320-179 clone provided in U.S. Patent No. 10,689,439. In some embodiments, the anti-TL1 A antibody is the 320-179 clone provided in U.S. Patent No. 10,689,439.

[0514] In some aspects of the disclosure, the anti-TL1 A antibody comprises a CDR-H1 having the sequence shown in SEQ ID NO: 65, a CDR-H2 having the sequence shown in SEQ ID NO: 66, a CDR-H3 having the sequence shown in SEQ ID NO:67, a CDR-L1 having the sequence shown in SEQ ID NO: 68, a CDR-L2 having the sequence shown in SEQ ID NO: 69, and a CDR-L3 having the sequence shown in SEQ ID NO: 70.

[0515] In some aspects of the disclosure, the anti-TL1 A 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.

[0516] In some aspects of the disclosure, the anti-TL1 A antibody comprises a heavy chain having the sequence shown in SEQ ID NO: 73, 75, 76, or 77 and / or a light chain having the sequence shown in SEQ ID NO:74. In some aspects of the disclosure, the anti-TL1 A antibody comprises a heavy chain having the sequence shown in SEQ ID NO: 73, 75, 76, or 77 and a light chain having the sequence shown in SEQ ID NO: 74. In some aspects of the disclosure, the anti-TL1 A antibody comprises a heavy chain having the sequence shown in SEQ ID NO: 73 and a light chain having the sequence shown in SEQ ID NO: 74. In some aspects of the disclosure, the anti-TL1 A antibody comprises a heavy chain having the sequence shown in SEQ ID NO: 75 and a light chain having the sequence shown in SEQ ID NO: 74. In some aspects of the disclosure, the anti-TL1 A antibody comprises a heavy chain having the sequence shown in SEQ ID NO: 76 and a light chain having the sequence shown in SEQ ID NO: 74. In some aspects of the disclosure, the anti-TL1 A antibody comprises a heavy chain having the sequence shown in SEQ ID NO: 77 and a light chain having the sequence shown in SEQ ID NO: 74.

[0517] In some aspects of the disclosure, the anti-TL1 A antibody is duvakitug / TEV-48574 (Sanofi / Teva Pharmaceuticals).PATENT

[0518] Attorney Docket No: 50474-373WO3

[0519] Genentech Docket No: P39855-WO-1

[0520] In some aspects of the disclosure, the anti-TL1 A antibody is C03V. C03V has been 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. An anti-TL1 A antibody for the treatment of asthma and inflammatory bowel disease. MAbs. 2018 May / Jun;10(4):664-677. Epub 2018 Mar 5. PMID: 29436901 ; PMCID: PMC5973687.

[0521] In some aspects of the disclosure, the anti-TL1 A antibody is SPY002 (Spyre Therapeutics). SPY002 has been described, for example, in Zhu, E., et al. "P911 Development and Characterization of SPY002, a Novel Extended Half-life Monoclonal Antibody Drug Candidate Targeting TL1 A for the Treatment of IBD." Journal of Crohn's and Colitis 18. Supplements (2024): i1666-i1666.

[0522] In some aspects, the anti-TL1 A antibody is SPY072 (Spyre Therapeutics). SPY072 has been described, for example, in Spyre Therapeutics, Spyre Therapeutics Announces Positive Interim Phase 1 Results for Two Next-Generation TL1 A Antibody Programs, and Provides Clinical Development Updates Expected to Deliver 9 Phase 2 Readouts, 2025 June.

[0523] In some aspects, the anti-TL1 A antibody is BB-TL1 A-VIAL-HLE (Battery Bio / Vial).

[0524] In some aspects, the anti-TL1 A antibody is ABBV-701 / FG-M701 (AbbVie / FutureGen). In some aspects of any of the methods, compositions, uses, and compositions for use provided herein, the anti-TL1 A antibody is an anti-TL1 A antibody provided in U.S. Patent Application Publication No.

[0525] 2025 / 0313644, which is incorporated herein by reference in its entirety.

[0526] In some aspects, the anti-TL1 A antibody is XmAb942 (Xencor). XmAb942 has been described, for example, in Hung et al., P1097 Phase 1 / 2 study to assess safety, tolerability, and efficacy of XmAb942 (anti-TL1 A) in healthy participants and participants with ulcerative colitis, Journal of Crohn's and Colitis, 2025 January; 19(Supplement_1).

[0527] In some aspects, the anti-TL1 A antibody is SSGJ-627 (Sunshine Guojian / 3SBio). In some aspects of any of the methods, compositions, uses, and compositions for use provided herein, the anti-TL1 A antibody is an anti-TL1 A antibody provided in International Patent Application Publication No. WO 2025 / 167705, which is incorporated herein by reference in its entirety.

[0528] In some aspects, the anti-TL1 A antibody is ABS-101 (Absci). In some aspects of any of the methods, compositions, uses, and compositions for use provided herein, the anti-TL1 A antibody is an anti-TL1 A antibody provided in International Patent Application Publication No. WO 2025 / 076081 , which is incorporated herein by reference in its entirety.

[0529] In some aspects, the anti-TL1 A antibody is BCD-261 (Biocad). In some aspects of any of the methods, compositions, uses, and compositions for use provided herein, the anti-TL1 A antibody is an anti-TL1 A antibody provided in International Patent Application Publication No. WO 2025 / 144089, which is incorporated herein by reference in its entirety.

[0530] In some aspects, the anti-TL1 A antibody is SY2434 (Symray Biopharma).

[0531] In some aspects, the anti-TL1 A antibody is LQ-083 (Novamab).

[0532] In some aspects, the anti-TL1A antibody is HXN-1001 (Helixon (Earendil Labs)). HXN-1001 has been described, for example, in Huang et al., P0835 Al-guided generation and development of HXN-1001 , a highly potent and half-life extended anti-TL1 A antibody, Journal of Crohn's and Colitis, 2025 January; 19(Supplement_1).PATENT

[0533] Attorney Docket No: 50474-373WO3

[0534] Genentech Docket No: P39855-WO-1

[0535] In some aspects, the anti-TL1 A antibody is GB-20 (Kexing Biopharm). In some aspects of any of the methods, compositions, uses, and compositions for use provided herein, the anti-TL1 A antibody is an anti-TL1 A antibody provided in Chinese Patent Application Publication No. CN120248119 or CN120271708, which are incorporated herein by reference in their entirety.

[0536] In some aspects, the anti-TL1 A antibody is GR-2303 (Genrix Bio). In some aspects of any of the methods, compositions, uses, and compositions for use provided herein, the anti-TL1 A antibody is an anti-TL1 A antibody provided in International Patent Application Publication No. WO 2025 / 112237, which is incorporated herein by reference in its entirety.

[0537] In some aspects, the anti-TL1 A antibody is GB-6537 (Generate Biomedicine).

[0538] In some aspects, the anti-TL1 A antibody is an anti-TL1 A monoclonal antibody developed by Chengdu Unovel Pharmaceutical Co., Ltd. In some aspects of any of the methods, compositions, uses, and compositions for use provided herein, the anti-TL1 A antibody is an anti-TL1 A antibody provided in International Patent Application Publication No. WO 2025 / 140188, which is incorporated herein by reference in its entirety.

[0539] B. Anti-DR3 antibodies

[0540] In some aspects, the methods of the present disclosure include the administration of an anti-DR3 antibody (e.g., an anti-DR3 antagonist antibody), e.g., the anti-TL1 A agent is an anti-DR3 antibody.

[0541] In some aspects, the anti-DR3 antibody is SL-325 (Shattuck Labs).

[0542] In some aspects, the anti-DR3 antibody is SL-425 (Shattuck Labs).

[0543] C. Anti-TL1A multispecific antibodies

[0544] In some aspects, the anti-TL1 A agent is a multispecific (e.g., bispecific or trispecific) antibody comprising at least one binding domain specific for TL1 A or DR3.

[0545] Table 4. Sequences of RO7837195 (PF-07261271)

[0546]

[0547] PATENT

[0548] Attorney Docket No: 50474-373WO3

[0549] Genentech Docket No: P39855-WO-1

[0550]

[0551] PATENT

[0552] Attorney Docket No: 50474-373WO3

[0553] Genentech Docket No: P39855-WO-1

[0554]

[0555] In some aspects, the anti-TL1 A agent is an anti-TL1 A bispecific antibody. For example, in some aspects, the anti-TL1 A agent is a bispecific antibody that binds to TL1 A and any one of interleukin-12 subunit p40 (p40), the p19 subunit of IL-23 (IL23p19), IL-23, LIGHT (TNFSF14), a4p7, and IL-10. In some aspects, the bispecific antibody binds to TL1 A and p40 and comprises (I) a TL1 A binding domain that comprises the following complementarity-determining regions (CDRs): (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 78 or SEQ ID NO: 88; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 79; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 80; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 81 ; (e) a CDR-L2 comprising the amino acidPATENT

[0556] Attorney Docket No: 50474-373WO3

[0557] Genentech Docket No: P39855-WO-1

[0558] sequence of SEQ ID NO: 82; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 83; and (II) a p40 binding domain that comprises the following CDRs: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 89; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 90; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 91 ; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 92; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 93; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 94. In some aspects, the CDR-H1 comprises or consists of the amino acid sequence of SEQ ID NO: 78. In other aspects, the CDR-H1 comprises or consists of the amino acid sequence of SEQ ID NO: 88.

[0559] In some aspects, the TL1 A binding domain of the bispecific antibody comprises (a) a heavy chain variable (VH) domain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 84 (e.g., having at least 96%, 97%, 98%, or 99% identity to SEQ ID NO: 84); and / or (b) a light chain variable (VL) domain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 85 (e.g., having at least 96%, 97%, 98%, or 99% identity to SEQ ID NO: 85).

[0560] In some aspects of the disclosure, the TL1 A binding domain of the bispecific antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 84 and / or comprises a VL domain comprising the amino acid sequence of SEQ ID NO: 85.

[0561] In some aspects of the disclosure, the TL1 A binding domain of the bispecific antibody comprises a VH having the sequence shown in SEQ ID NO: 84 and a VL having the sequence shown in SEQ ID NO: 85.

[0562] In some aspects, the TL1 A binding domain of the bispecific antibody comprises (a) a heavy chain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 86 (e.g., having at least 96%, 97%, 98%, or 99% identity to SEQ ID NO: 86); and / or (b) a light chain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 87 (e.g., having at least 96%, 97%, 98%, or 99% identity to SEQ ID NO: 87).

[0563] In some aspects of the disclosure, the TL1 A binding domain of the bispecific antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 86 and / or comprises a VL domain comprising the amino acid sequence of SEQ ID NO: 87.

[0564] In some aspects of the disclosure, the TL1 A binding domain of the bispecific antibody comprises a VH having the sequence shown in SEQ ID NO: 86 and a VL having the sequence shown in SEQ ID NO: 87.

[0565] In some aspects, the p40 binding domain of the bispecific antibody comprises (a) a heavy chain variable (VH) domain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 95 (e.g., having at least 96%, 97%, 98%, or 99% identity to SEQ ID NO: 95); and / or (b) a light chain variable (VL) domain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 96 (e.g., having at least 96%, 97%, 98%, or 99% identity to SEQ ID NO: 96).

[0566] In some aspects of the disclosure, the p40 binding domain of the bispecific antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 95 and / or comprises a VL domain comprising the amino acid sequence of SEQ ID NO: 96.PATENT

[0567] Attorney Docket No: 50474-373WO3

[0568] Genentech Docket No: P39855-WO-1

[0569] In some aspects of the disclosure, the p40 binding domain of the bispecific antibody comprises a VH having the sequence shown in SEQ ID NO: 95 and a VL having the sequence shown in SEQ ID NO: 96.

[0570] In some aspects, the p40 binding domain of the bispecific antibody comprises (a) a heavy chain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 97 (e.g., having at least 96%, 97%, 98%, or 99% identity to SEQ ID NO: 97); and / or (b) a light chain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 98 (e.g., having at least 96%, 97%, 98%, or 99% identity to SEQ ID NO: 98).

[0571] In some aspects of the disclosure, the p40 binding domain of the bispecific antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 97 and / or comprises a VL domain comprising the amino acid sequence of SEQ ID NO: 98.

[0572] In some aspects of the disclosure, the p40 binding domain of the bispecific antibody comprises a VH having the sequence shown in SEQ ID NO: 97 and a VL having the sequence shown in SEQ ID NO: 98.

[0573] In some aspects of the disclosure, the bispecific antibody comprises (I) a TL1 A binding domain that comprises (a) a VH domain comprising the amino acid sequence of SEQ ID NO: 84 and (b) a VL domain comprising the amino acid sequence of SEQ ID NO: 85; and (II) a p40 binding domain that comprises (a) a VH domain comprising the amino acid sequence of SEQ ID NO: 95 and (b) a VL domain comprising the amino acid sequence of SEQ ID NO: 96.

[0574] In some aspects of the disclosure, the bispecific antibody comprises (a) a first polypeptide comprising the amino acid sequence of SEQ ID NO: 86; (b) a second polypeptide comprising the amino acid sequence of SEQ ID NO: 87; (c) a third polypeptide comprising the amino acid sequence of SEQ ID NO: 97; and (d) a fourth polypeptide comprising the amino acid sequence of SEQ ID NO: 98.

[0575] In some aspects of the disclosure, the bispecific antibody is RO7837195 (also known as PF-07261271 or p40TL1 A-0033). The structure of RO7837195 is described in PCT Publication No. WO 2023 / 220663 and in U.S. Patent Application Publication No. US 2024 / 0059799 A1 , which are incorporated herein by reference for all purposes.

[0576] In some aspects, the bispecific antibody binds to TL1 A and the p19 subunit of IL-23 (IL23p19). In some aspects, the bispecific antibody is HXN-1003 (Sanofi / Earendil Labs). HXN-1003 targets TL1 A and IL-23. HXN-1003 has been described, for example, in Huang et al., P1114 Engineering and Development of a Novel Bispecific Antibody Targeting IL-23 and TL1 A, Journal of Crohn's and Colitis, 2025 January; 19(Supplement_1).

[0577] In some aspects, the bispecific antibody is an anti-TL1 A / anti-IL-23 antibody developed by Generate Biomedicine.

[0578] In some aspects, the bispecific antibody is LQ-080 (Novamab). LQ-080 targets TL1 A and IL-23p19. LQ-080 has been described, for example, in Wan et al., P0640 Development and characterization of LQ080, a novel extended half-life bispecific TL1 A / IL-23 p19 single domain antibody for the treatment of IBD, Journal of Crohn's and Colitis, 2025 January; 19(Supplement_1).

[0579] In some aspects, the bispecific antibody is an anti-TL1 A / anti-IL-23p19 antibody developed by Xencor (XmAb).PATENT

[0580] Attorney Docket No: 50474-373WO3

[0581] Genentech Docket No: P39855-WO-1

[0582] In some aspects, the bispecific antibody is GB-24 (Kexing Biopharm). GB-24 targets TL1 A and LIGHT (TNFSF14).

[0583] In some aspects, the bispecific antibody is SIM-0709 (Simcere Pharma). SIM-0709 targets TL1 A and IL-23.

[0584] In some aspects, the bispecific antibody is HXN-1002 (Sanofi / Earendil Labs). HXN-1002 targets TL1 A and a4p7. HXN-1002 has been described, for example, in Ran et al., P0848 Engineering and Development of a Novel Bispecific Antibody Targeting both TL1 A and a4p7 for the Treatment of IBD, Journal of Crohn's and Colitis, 2025 January; 19(Supplement_1 ).

[0585] In some aspects, the bispecific antibody is LQ-081 (Novamab). LQ-081 targets TL1 A and a4p7. In some aspects, the bispecific antibody is VTC-890 (Virtici). VTC-890 targets TL1 A and LIGHT. In some aspects, the bispecific antibody was developed by Shattuck Labs and targets DR3 and another target.

[0586] In some aspects, the bispecific antibody is FPE-022 (Fapon Biopharma). FPE-022 targets TL1 A and IL-10.

[0587] In some aspects, the anti-TL1 A agent is an anti-TL1 A trispecific antibody. For example, in some aspects, the anti-TL1 A agent is a trispecific antibody that binds to TL1 A and one or both of IL-23 and a4p7.

[0588] In some aspects, the trispecific antibody is LQ-082 (Novamab). LQ-082 targets TL1 A, IL-23, and a4p7.

[0589] D. Anti-TL 1A antibody combinations

[0590] In some aspects, the anti-TL1 A agent is a combination (e.g., mixture) of two or more antibodies, wherein at least one of the antibodies is an anti-TL1 A antibody or an anti-DR3 antibody.

[0591] In some aspects, the anti-TL1 A agent is SPY120 (Spyre Therapeutics); SPY120 is a combination of SPY001 (anti-a4p7) and SPY002 (anti-TL1 A).

[0592] In some aspects, the anti-TL1 A agent is SPY230 (Spyre Therapeutics); SPY230 is a combination of SPY003 (anti-IL23) and SPY002 (anti-TL1 A).

[0593] E. Anti-TL1 A peptides

[0594] In some aspects, the anti-TL1 A agent is a polypeptide that inhibits the activity of TL1 A, either directly (e.g., by binding to TL1 A) or indirectly (e.g., by binding to another protein in the TL1 A pathway, e.g., death receptor 3 (DR3)). The anti-TL1 A polypeptide may be, e.g., orally administered, intravenously administered, or subcutaneously administered.

[0595] In some aspects, the anti-TL1 A polypeptide is a TL1 A inhibitor developed by Nimble Therapeutics.

[0596] F. Anti-TL1 A small molecules

[0597] In some aspects, the anti-TL1 A agent is a small molecule that inhibits the activity of TL1 A, either directly (e.g., by binding to TL1 A) or indirectly (e.g., by binding to another protein in the TL1 A pathway,PATENT

[0598] Attorney Docket No: 50474-373WO3

[0599] Genentech Docket No: P39855-WO-1

[0600] e.g., death receptor 3 (DR3)). The anti-TL1 A small molecule may be, e.g., orally administered, intravenously administered, or subcutaneously administered.

[0601] In some aspects, the anti-TL1 A small molecule is ENV-6946 I ESN-X1 (Enveda), a NLRP3 / TL1 A pathway+ inhibitor.

[0602] In some aspects, the anti-TL1 A small molecule is ESN-X2 (Enveda), a NLRP3 / TL1 A pathway+ inhibitor.

[0603] In some aspects, the anti-TL1 A small molecule is ENV-096 I ESN-X (Enveda), a TL1 A pathways-inhibitor.

[0604] In some aspects, the anti-TL1 A small molecule is ESN-T (Enveda), a TL1 A antagonist.

[0605] In some aspects, the anti-TL1 A small molecule is MORF SMI (Morphic I Eli Lilly), a small molecule inhibitor of, e.g., IL-23 and TL1 A.

[0606] In some aspects, the anti-TL1 A small molecule is an allosteric inhibitor of TL1 A developed by Psivant Therapeutics.

[0607] IV. Articles of Manufacture and Kits

[0608] In another aspect of the invention, an article of manufacture containing materials useful for the treatment, prevention and / or diagnosis of the disorders described above (e.g., inflammatory bowel disease (IBD), e.g., ulcerative colitis (UC) or Crohn’s disease (CD)) is provided. The article of manufacture comprises a container and a label or package insert on or associated with the container. Suitable containers include, for example, bottles, vials, syringes, IV solution bags, etc. The containers may be formed from a variety of materials such as glass or plastic. The container holds a composition (e.g., a composition comprising an anti-TL1 A agent (e.g., anti-TL1 A antibody)) which is by itself or combined with another composition effective for treating, preventing and / or diagnosing the condition and may have a sterile access port (for example the container may be an intravenous solution bag or a vial having a stopper pierceable by a hypodermic injection needle). At least one active agent in the composition is an agent (e.g., antibody) of the invention (e.g., an anti-TL1 A antibody, e.g., afimkibart). The label or package insert indicates that the composition is used for treating the condition of choice (e.g., IBD, e.g., UC or CD). Moreover, the article of manufacture may comprise (a) a first container with a composition contained therein, wherein the composition comprises an agent (e.g., antibody) of the invention; and (b) a second container with a composition contained therein, wherein the composition comprises a further therapeutic agent. The article of manufacture in this aspect of the invention may further comprise a package insert indicating that the compositions can be used to treat a particular condition (e.g., IBD, e.g., UC or CD). Alternatively, or additionally, the article of manufacture may further comprise a second (or third) container comprising a pharmaceutically-acceptable buffer, such as bacteriostatic water for injection (BWFI), phosphate-buffered saline, Ringer's solution and dextrose solution. It may further include other materials desirable from a commercial and user standpoint, including other buffers, diluents, filters, needles, and syringes.

[0609] The disclosure also provides kits comprising any or all of the anti-TL1 A antibodies described herein. Kits of the disclosure include one or more containers comprising an anti-TL1 A agent (e.g., anti-TL1 A antibody) described herein and instructions for use in accordance with any of the methods of thePATENT

[0610] Attorney Docket No: 50474-373WO3

[0611] Genentech Docket No: P39855-WO-1

[0612] disclosure described herein. Generally, these instructions comprise a description of administration of the anti-TL1 A agent (e.g., anti-TL1 A antibody) for the above-described therapeutic treatments. In some aspects, kits are provided for producing a single-dose administration unit. In certain aspects, the kit can contain both a first container having a dried protein and a second container having an aqueous formulation. In certain aspects, kits containing single and multi-chambered pre-filled syringes (e.g., liquid syringes and lyosyringes) are included.

[0613] The instructions relating to the use of an anti-TL1 A agent (e.g., anti-TL1 A antibody) generally include information as to dosage, dosing schedule, and route of administration for the intended treatment. The containers may be unit doses, bulk packages (e.g., multi dose packages) or sub-unit doses.

[0614] Instructions supplied in the kits of the disclosure are typically written instructions on a label or package insert (e.g., a paper sheet included in the kit), but machine-readable instructions (e.g., instructions carried on a magnetic or optical storage disk) are also acceptable.

[0615] The kits of this disclosure are in suitable packaging. Suitable packaging includes, but is not limited to, vials, bottles, jars, flexible packaging (e.g., sealed Mylar or plastic bags), and the like. Also contemplated are packages for use in combination with a specific device, such as an inhaler, nasal administration device (e.g., an atomizer) or an infusion device such as a minipump. A kit may have a sterile access port (for example the container may be an intravenous solution bag or a vial having a stopper pierceable by a hypodermic injection needle). The container may also have a sterile access port (for example the container may be an intravenous solution bag or a vial having a stopper pierceable by a hypodermic injection needle). At least one active agent in the composition is an anti-TL1 A agent (e.g., anti-TL1 A antibody). The container may further comprise a second pharmaceutically active agent.

[0616] Kits may optionally provide additional components such as buffers and interpretive information. Normally, the kit comprises a container and a label or package insert(s) on or associated with the container.

[0617] V. Compositions and Formulations

[0618] A. Compositions

[0619] In a further aspect, provided are pharmaceutical compositions comprising an effective amount of an anti-TL1 A agent (e.g., anti-TL1 A antibody) as described herein, and such pharmaceutical compositions for use in any of the methods of treatment provided herein. In one aspect, a pharmaceutical composition comprises any of the antibodies provided herein and a pharmaceutically acceptable carrier. In another aspect, a pharmaceutical composition comprises any of the antibodies provided herein and at least one additional therapeutic agent, e.g., as described below.

[0620] Pharmaceutical compositions (formulations) of an anti-TL1 A agent (e.g., anti-TL1 A antibody) as described herein can be prepared by combining the agent (e.g., antibody) with pharmaceutically acceptable carriers or excipients known to the skilled person. See, for example Remington's Pharmaceutical Sciences 16th edition, Osol, A. Ed. (1980) and Falconer R.J., Biotechnology Advances 37: 107412 (2019). Exemplary pharmaceutical compositions of an anti-TL1 A agent (e.g., anti-TL1 A antibody) as described herein may be lyophilized, aqueous, frozen, etc.PATENT

[0621] Attorney Docket No: 50474-373WO3

[0622] Genentech Docket No: P39855-WO-1

[0623] Pharmaceutically acceptable carriers are generally non-toxic to recipients at the dosages and concentrations employed, and include, but are not limited to: buffers such as histidine, phosphate, citrate, acetate, and other organic acids; antioxidants including ascorbic acid and methionine; preservatives (such as octadecyldimethylbenzyl ammonium chloride; hexamethonium chloride; benzalkonium chloride; benzethonium chloride; phenol, butyl or benzyl alcohol; alkyl parabens such as methyl or propyl paraben; catechol; resorcinol; cyclohexanol; 3-pentanol; and m-cresol); low molecular weight (less than about 10 residues) polypeptides; 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 dextrins; chelating agents such as EDTA; sugars such as sucrose, mannitol, trehalose or sorbitol; salt-forming counter-ions such as sodium; metal complexes (e.g., Zn-protein complexes); and / or non-ionic surfactants such as polyethylene glycol (PEG).

[0624] The pharmaceutical composition herein may also contain more than one active ingredient as necessary for the particular indication being treated, preferably those with complementary activities that do not adversely affect each other. Such active ingredients are suitably present in combination in amounts that are effective for the purpose intended.

[0625] The pharmaceutical compositions to be used for in vivo administration are generally sterile. Sterility may be readily accomplished, e.g., by filtration through sterile filtration membranes.

[0626] The anti-TL1 A agent (e.g., anti-TL1 A antibody), and compositions thereof, can also be used in conjunction with, or administered separately, simultaneously, or sequentially with other agents that serve to enhance and / or complement the effectiveness of the agents.

[0627] B. Formulations

[0628] Therapeutic formulations of the anti-TL1 A agent (e.g., anti-TL1 A antibody) used in accordance with the present disclosure are prepared for storage by mixing the protein having the desired degree of purity with optional pharmaceutically acceptable carriers, excipients or stabilizers (Remington, The Science and Practice of Pharmacy 20th Ed. Mack Publishing, 2000), in the form of lyophilized formulations or aqueous solutions. Acceptable carriers, excipients, or stabilizers are nontoxic to recipients at the dosages and concentrations employed, and may comprise buffers such as phosphate, citrate, and other organic acids; salts such as sodium chloride; antioxidants including ascorbic acid and methionine; preservatives (such as octadecyldimethylbenzyl ammonium chloride; hexamethonium chloride; benzalkonium chloride, benzethonium chloride; phenol, butyl or benzyl alcohol; alkyl parabens, such as methyl or propyl paraben; catechol; resorcinol; cyclohexanol; 3-pentanol; and m-cresol); low molecular weight (less than about 10 residues) polypeptides; 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 dextrins; chelating agents such as EDTA; sugars such as sucrose, mannitol, trehalose or sorbitol; salt-forming counter-ions such as sodium; metal complexes (e.g. Zn-protein complexes); and / or non-ionic surfactants such as TWEEN™, PLURONICS™ or polyethylene glycol (PEG).PATENT

[0629] Attorney Docket No: 50474-373WO3

[0630] Genentech Docket No: P39855-WO-1

[0631] Liposomes that may contain the anti-TL1 A agent (e.g., anti-TL1 A antibody) are prepared by methods known in the art, such as 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. Pat. Nos. 4,485,045 and 4,544,545. Liposomes with enhanced circulation time are disclosed in U.S. Patent No. 5,013,556.

[0632] Particularly useful liposomes can be generated by the reverse phase evaporation method with a lipid composition comprising phosphatidylcholine, cholesterol and PEG-derivatized phosphatidylethanolamine (PEG-PE). Liposomes are extruded through filters of defined pore size to yield liposomes with the desired diameter.

[0633] The active ingredients may also be entrapped in microcapsules prepared, for example, by coacervation techniques or by interfacial polymerization, for example, hydroxymethylcellulose or gelatinmicrocapsules and poly-(methylmethacrylate) microcapsules, respectively, in colloidal drug delivery systems (for example, liposomes, albumin microspheres, microemulsions, nano-particles and nanocapsules) or in macroemulsions. Such techniques are disclosed in Remington, The Science and Practice of Pharmacy 20th Ed. Mack Publishing (2000).

[0634] Sustained-release preparations may be prepared. Suitable examples of sustained-release preparations include semipermeable matrices of solid hydrophobic polymers containing the agent (e.g., antibody), which matrices are in the form of shaped articles, e.g. films, or microcapsules. Examples of sustained-release matrices include polyesters, hydrogels (for example, poly(2-hydroxyethyl-methacrylate), or poly(vinylalcohol)), polylactides (U.S. Pat. No. 3,773,919), copolymers of L-glutamic acid and 7 ethyl-L-glutamate, non-degradable ethylene-vinyl acetate, degradable lactic acid-glycolic acid copolymers such as the LUPRON DEPOT™ (injectable microspheres composed of lactic acid-glycolic acid copolymer and leuprolide acetate), sucrose acetate isobutyrate, and poly-D-(-)-3-hydroxybutyric acid.

[0635] The formulations to be used for in vivo administration must be sterile. This is readily accomplished by, for example, filtration through sterile filtration membranes. Therapeutic anti-TL1 A agent (e.g., antibody) compositions are generally placed into a container having a sterile access port, for example, an intravenous solution bag or vial having a stopper pierceable by a hypodermic injection needle.

[0636] The compositions according to the present disclosure may be in unit dosage forms such as tablets, pills, capsules, powders, granules, solutions or suspensions, or suppositories, for oral, parenteral or rectal administration, or administration by inhalation or insufflation.

[0637] For preparing solid compositions such as tablets, the principal active ingredient is mixed with a pharmaceutical carrier, e.g. conventional tableting ingredients such as corn starch, lactose, sucrose, sorbitol, talc, stearic acid, magnesium stearate, dicalcium phosphate or gums, and other pharmaceutical diluents, e.g. water, to form a solid preformulation composition containing a homogeneous mixture of a compound of the present disclosure, or a non-toxic pharmaceutically acceptable salt thereof. When referring to these preformulation compositions as homogeneous, it is meant that the active ingredient is dispersed evenly throughout the composition so that the composition may be readily subdivided into equally effective unit dosage forms such as tablets, pills and capsules. This solid preformulation composition is then subdivided into unit dosage forms of the type described above containing from about 0.1 to about 500 mg of the active ingredient of the present disclosure. The tablets or pills of the novelPATENT

[0638] Attorney Docket No: 50474-373WO3

[0639] Genentech Docket No: P39855-WO-1

[0640] composition can be coated or otherwise compounded to provide a dosage form affording the advantage of prolonged action. For example, the tablet or pill can comprise an inner dosage and an outer dosage component, the latter being in the form of an envelope over the former. The two components can be separated by an enteric layer that serves to resist disintegration in the stomach and permits the inner component to pass intact into the duodenum or to be delayed in release. A variety of materials can be used for such enteric layers or coatings, such materials including a number of polymeric acids and mixtures of polymeric acids with such materials as shellac, cetyl alcohol and cellulose acetate.

[0641] Suitable surface-active agents include, in particular, non-ionic agents, such as polyoxyethylenesorbitans (e.g. Tween™ 20, 40, 60, 80 or 85) and other sorbitans (e.g. Span™ 20, 40, 60, 80 or 85). Compositions with a surface-active agent will conveniently comprise between 0.05 and 5% surface-active agent, and can be between 0.1 and 2.5%. It will be appreciated that other ingredients may be added, for example mannitol or other pharmaceutically acceptable vehicles, if necessary.

[0642] Suitable emulsions may be prepared using commercially available fat emulsions, such as INTRALIPID™, LIPOSYN™, INFONUTROL™, LIPOFUNDIN™ and LIPIPHYSAN™. The active ingredient may be either dissolved in a pre-mixed emulsion composition or alternatively it may be dissolved in an oil (e.g. soybean oil, safflower oil, cottonseed oil, sesame oil, corn oil or almond oil) and an emulsion formed upon mixing with a phospholipid (e.g. egg phospholipids, soybean phospholipids or soybean lecithin) and water. It will be appreciated that other ingredients may be added, for example glycerol or glucose, to adjust the tonicity of the emulsion.

[0643] Suitable emulsions will typically contain up to 20% oil, for example, between 5 and 20%. The fat emulsion can comprise fat droplets between 0.1 and 1 .0 pm, particularly 0.1 and 0.5 pm, and have a pH in the range of 5.5 to 8.0.

[0644] The emulsion compositions can be those prepared by mixing an anti-TL1 A agent (e.g., anti-TL1 A antibody) with INTRALIPID™ or the components thereof (soybean oil, egg phospholipids, glycerol and water).

[0645] Compositions for inhalation or insufflation include solutions and suspensions in pharmaceutically acceptable, aqueous or organic solvents, or mixtures thereof, and powders. The liquid or solid compositions may contain suitable pharmaceutically acceptable excipients as set out above. In some aspects, the compositions are administered by the oral or nasal respiratory route for local or systemic effect. Compositions in preferably sterile pharmaceutically acceptable solvents may be nebulised by use of gases. Nebulised solutions may be breathed directly from the nebulising device or the nebulising device may be attached to a face mask, tent or intermittent positive pressure breathing machine. Solution, suspension or powder compositions may be administered, preferably orally or nasally, from devices which deliver the formulation in an appropriate manner.

[0646] In aspects that refer to a method of treating IBD as described herein, such aspects are also further aspects of an anti-TL1 A agent (e.g., anti-TL1 A antibody) for use in that treatment, or alternatively of the use of an anti-TL1 A agent (e.g., anti-TL1 A antibody) in the manufacture of a medicament for use in that treatment.PATENT

[0647] Attorney Docket No: 50474-373WO3

[0648] Genentech Docket No: P39855-WO-1

[0649] VI. Examples

[0650] Example 1. Dose and Regimen for Afimkibart in Pediatric Patients with Ulcerative Colitis or Crohn’s Disease

[0651] A. Background

[0652] Afimkibart is a fully human immunoglobulin G1 (lgG1 ) neutralizing monoclonal antibody (mAb) against tumor necrosis factor-like ligand 1 A (TL1 A). TL1 A plays a central role in the regulation of gut mucosal immunity and participates in immunological and fibrosis pathways involved in inflammatory bowel disease (IBD) pathogenesis by binding its receptor, 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 TL1 A prevents the binding and signaling of TL1 A to death receptor 3 on immune cells, leading to anti-inflammatory and anti-fibrotic effects. The direct relevance of the anti-TL1 A mechanism of action having potential for both anti-inflammatory and anti-fibrotic effects may be particularly important for patients with CD, who often develop complications such as strictures, fistulae, and abscesses. In vitro studies and rodent colitis models have shown that anti-TL1 A antibodies can reduce tissue fibrosis and clinical disease scores (Shih et al., Mucosal Immunol, 7: 1492-1503, 2014; Clarke et al., MAbs, 10: 664-677, 2018). This is particularly important for patients with CD, who often progress to develop devastating clinical complications such as strictures or fistulae.

[0653] There is an ongoing high unmet medical need in the treatment of pediatric patients with UC (e.g., moderately to severely active UC) and CD. Therapeutic options have expanded substantially over the past decade, with biologies (e.g., anti-tumor necrosis factor (TNF), anti-IL-12 / 23, and anti-integrin molecule mAbs) and small molecule treatments (e.g., Janus kinase (JAK) inhibitors and sphingosine 1 phosphate (S1 P) receptor modulators) now available in addition to conventional therapies.

[0654] However, only two therapies have been approved for UC and CD in children (adalimumab and infliximab, both anti-TNFs). While the use of anti-TNFs has provided significant benefits to pediatric patients having UC, some patients fail to respond at all (primary nonresponse) and the majority of patients who initially respond lose that effect within 5 years (secondary nonresponse; Fumery et al., J Crohns Colitis., 18: 1615-1621, 2024). Despite these concerning figures, consensus guidelines for the management of pediatric anti-TNF-refractory UC do not exist.

[0655] In addition to inadequately controlling disease, current treatments have various risks and adverse drug reactions, which must be balanced with patient-specific considerations to mitigate safety issues (Bhat et al., Inflamm Bowel Dis., 30: 829-843, 2024; Turner et al., J Pediatr Gastroenterol Nutr., 55: 340-361, 2012).

[0656] New treatment options that offer reliable and safe induction and maintenance of remission thus remain an area of need for the treatment of pediatric UC and CD.

[0657] Thus, a high unmet medical need remains for treatments with better benefit-risk profiles that attenuate inflammation and clinical sequelae and provide sustained control to improve the long-term prognosis of patients (e.g., pediatric patients) with IBD (e.g., UC or CD).

[0658] Dose regimens of afimkibart appropriate for the pediatric population with ulcerative colitis (UC) or Crohn’s disease (CD) are provided herein. Details of pediatric studies that assess the safety and efficacy of these dosing regimens are also provided.PATENT

[0659] Attorney Docket No: 50474-373WO3

[0660] Genentech Docket No: P39855-WO-1

[0661] The pediatric dosing regimens were selected, at least in part, on the basis of a population pharmacokinetic / pharmacodynamic (popPK / PD) model established with healthy subjects and participants with an IBD (UC) (Phase Ila study NCT04269538, Phase I study NCT05107492, and Phase lib study NCT04090411), immunogenicity data from the adult patient population with UC, and exposure-response analyses conducted with Phase lib data.

[0662] The PK of afimkibart following intravenous (IV) or subcutaneous (SC) administration has been well-characterized in adult patients with UC and is consistent with typical IgG 1 mAb therapies. Data from more than 350 subjects were available for the PK analysis (about 80% with UC, age range of 18 to 73 years, and body weight range of 33.9 to 130 kg). As expected for an lgG1 type monoclonal antibody (mAb) in this patient population, body weight and baseline serum albumin were identified as the main covariates that can explain variability in afimkibart exposure. Also, several model parameters were influenced by immunogenicity (level of anti-drug antibody titers).

[0663] Participants in the pediatric studies in UC (CA45905) and CD (CP45906) are divided into subgroups based on:

[0664] • Body weight (BW): low body weight (low BW) category from >10 to <35 kg, and high body weight (high BW) category >35 kg.

[0665] • Dose: a low IV dose and a high IV dose are evaluated for the induction treatment period (Week 0 to Week 12), and a low SC dose and a high SC dose are evaluated for the maintenance treatment period (Week 12 to Week 52).

[0666] In the pediatric studies, the proposed low and high IV doses for the induction treatment period, along with the proposed low and high SC doses for the maintenance treatment period, are expected to achieve drug exposures across the entire range of body weights for pediatric subjects that are comparable to drug exposures for adult subjects in the Phase ll / lll studies.

[0667] Also, dose regimens for pediatric groups in the studies (e.g., low BW and high BW) have been calculated by scaling established adult doses using body weight and have been selected to achieve systemic exposures of afimkibart regimens that are safe and efficacious in adults with UC. In addition to BW, covariates such as immunogenicity and serum albumin have been shown to influence the PK of afimkibart in adults, and it is assumed that this will also occur in children.

[0668] B. Dosing Regimens and Rationale

[0669] The pediatric doses and dosing regimens are provided in Table 5, below.

[0670] Table 5. Dose and Regimen for Afimkibart in Pediatric Patients with UC or CD

[0671] > < >

[0672]

[0673] PATENT

[0674] Attorney Docket No: 50474-373WO3

[0675] Genentech Docket No: P39855-WO-1

[0676]

[0677] Afimkibart is administered in an induction phase that is followed by a maintenance phase.

[0678] Four doses for the induction phase are evaluated: (i) a 500 mg dose for patients having a high BW (“high BW, Dose B (high dose)”), (ii) a 16 mg / kg dose (not exceeding 500 mg) for patients having a low BW (“low BW, Dose B (high dose)”), (iii) a 250 mg dose for patients having a high BW (“high BW, Dose A (low dose)”), and (iv) an 8 mg / kg dose (not exceeding 250 mg) for patients having a low BW (“low BW, Dose A (low dose)”). For all induction phase dosing regimens in the pediatric study, afimkibart is administered intravenously on Weeks 0, 2, 6, and 10.

[0679] Further, four doses for the maintenance phase are evaluated: (i) a 450 mg dose for patients having a high BW (“high BW, Dose B (high dose)”), (ii) a 150 mg dose for patients having a low BW (“low BW, Dose B (high dose)”), (iii) a 150 mg dose for patients having a high BW (“high BW, Dose A (low dose)”), and (iv) a 50 mg dose for patients having a low BW (“low BW, Dose A (low dose)”). For all maintenance phase dosing regimens in the pediatric study, afimkibart is administered subcutaneously every four weeks (Q4W) beginning on Week 12 and ending on Week 52.

[0680] All participants have the opportunity to participate in the optional open-label extension (OLE) phase of the study with access to afimkibart and monitoring, provided they meet specified eligibility criteria.

[0681] Participants may be eligible to enter OLE after completion of the 40-week maintenance phase and upon completion of the Week 52 assessments. The first OLE visit for participants entering from the maintenance phase is at Week 56, and participants continue in the OLE phase on the Q4W dose regimen (150 mg for low body weight or 450 mg for high body weight SC Q4W). Participants at Week 52 who do meet response criteria (e.g., UC patients who are not in clinical remission defined as mMS < 2 with SFS < 0 or 1 , RBS = 0, and ES < 0 or 1) and are not on open-label afimkibart enter the OLE at Q2W dosing frequency. Participants may also be eligible to dose-intensify for 12 weeks to Q2W dose B regimen if they meet disease worsening criteria (DWC) during OLE and have not previously met DWC throughout the study.

[0682] / . Rationale for the high IV doses and regimens (Dose B) in the induction phase

[0683] High BW, high dose regimen

[0684] The 500 mg IV dose and regimen for participants with high BW (>35 kg BW) (Table 5; “high BW, high dose” regimen) is currently being evaluated in Phase III studies in adults with UC (GA45329 and GA45330 (NCT06589986 and NCT06588855) and CD (GA45331 and GA45332 (NCT06819878 and NCT06819891))). As is shown in Figs. 1 A and 1 B, this dose and regimen in the pediatric population provided predicted exposure levels that are comparable to those predicted for the 500 mg IV regimen in the ongoing Phase III Studies in adults.PATENT

[0685] Attorney Docket No: 50474-373WO3

[0686] Genentech Docket No: P39855-WO-1

[0687] The “high BW, high dose” regimen achieves afimkibart exposure levels that fall between those of two safe and effective regimens: (i) the regimen of 500 mg afimkibart administered IV every two weeks (Q2W) for 7 doses used in the Phase Ila study (B7541002 (NCT02840721)), and (ii) the regimen of 450 mg afimkibart administered SC every four weeks (Q4W) used in the Phase lib study (B7541007 (NCT04090411)).

[0688] The “high BW, high dose” regimen aims to increase the likelihood of maximal blockade of TL1 A in inflamed tissues in conditions such as UC and CD that show higher TL1 A expression in gut tissue (Meng et al., PNAS, 120:e2120771120, 2023), as well as to mitigate the impact of immunogenicity on PK, efficacy, and safety. IV dosing in the Phase Ila study was associated with lower anti-drug antibody (ADA) titers and a delayed median time to first ADA as compared to SC dosing (Phase lib study).

[0689] Low BW, high dose regimen

[0690] The 16 mg / kg IV dose and regimen for participants with >10 to <35 kg BW (Table 5; “low BW, high dose” regimen) is predicted to achieve exposure levels comparable to those of the 500 mg IV regimen for participants with >35 kg BW (Figs. 1 A and 1 B). The dose for patients treated according to this dosing regimen is not to exceed 500 mg. The BW-based dosing approach for the IV induction regimen in the low BW group is selected to reduce the risk of overexposure and high interindividual variability in participants with lower BWs. To demonstrate safety coverage of the 500 mg IV (>35 kg BW) and 16 mg / kg IV (> 10 to <35 kg BW) dose regimens in pediatric participants, reference is made to the 500 mg IV Q2W regimen (7 doses) as studied in the Phase Ila trial in adults with UC (B7541002).

[0691] Predicted concentration-time profiles

[0692] Predicted concentration-time profiles for the 500 mg IV and 16 mg / kg IV dose regimens in pediatric participants are presented in Figs. 9A and 9B. For pediatric participants, simulations were performed using post hoc parameters from adult participants in Studies B7541002 and B7541007 and duplicated randomly by body weight band of 10 kg. For adult participants, simulations (>40 kg in Fig. 9A and 40-60 kg in Fig. 9B) were performed using post hoc parameters from Studies B7541002 and B7541007.

[0693] During the induction phase, peak concentrations (Cmax) in pediatric participants are predicted to be 20-30% higher than those projected for adults, yet they remain within values that have demonstrated to be safe considering that predicted Cmax at Week 10 for pediatric participants are within observed Cmax values at Week 12 for adult participants in the Phase Ila Study in UC. Predicted area under the concentration-time curve during dosing intervals (AUCtau) for pediatric participants are within or below values for adult participants.

[0694] In Cohort 2, dosing of afimkibart in the low BW Group 4 (16 mg / kg IV on Weeks 0, 2, 6 and 10, followed by 150 mg SC every 4 weeks (Q4W) from Week 12 through Week 52) is permitted after the interim PK analysis has been conducted with Cohort 1 data (Group 1 , 2 and 3).PATENT

[0695] Attorney Docket No: 50474-373WO3

[0696] Genentech Docket No: P39855-WO-1

[0697]

[0698] High BW, low dose regimen

[0699] The 250 mg IV dose and regimen for participants with >35 kg BW (Table 5; “high BW, low dose” regimen) is predicted to achieve efficacious exposure levels based on data from the Phase lib study in adults with UC. It is predicted to achieve afimkibart exposure levels that fall between those of two effective regimens: the regimens of (i) 150 mg and (ii) 450 mg afimkibart administered SC every four weeks (Q4W) used in the Phase lib study during induction. Figs. 2A and 2B compare the exposure of the proposed IV regimen in pediatric patients with the 150 mg SC Q4W regimen evaluated in the Phase lib UC study in adults.

[0700] Low BW, low dose regimen

[0701] The 8 mg / kg IV dose and regimen for participants with >10 to <35 kg BW is predicted to achieve exposure levels comparable to those of the 250 mg IV regimen for participants with >35 kg BW (Figs. 2A and 2B).

[0702] Hi. Rationale for the high SC doses and regimens in the maintenance phase (Dose B) High BW, high dose regimen

[0703] The 450 mg SC dose and regimen for participants with >35 kg BW (Table 5; “high BW, high dose” regimen) is the highest regimen evaluated in the Phase lib study in adults with UC (B7541007 (NCT04090411)) and is currently being evaluated in the Phase III study in adults with UC (GA45329 (NCT06589986)). This regimen is supported by the clinically meaningful efficacy response, as well as by its favorable safety profile in Study B7541007 (NCT04090411). The proposed SC regimen for pediatric patients is expected to achieve exposure levels that are predicted to be safe and efficacious based on the highest dose evaluated in the Phase lib UC study (NCT040904117) in adults, i.e. 450 mg SC Q4W (Figs.

[0704] 3A and 3B).

[0705] Low BW, high dose regimen

[0706] The 150 mg SC dose and regimen for participants with >10 to <35 kg BW (Table 5; “low BW, high dose” regimen) is predicted to achieve exposure levels comparable to those of the 450 mg SC regimen for participants with >35 kg BW (Figs. 3A and 3B).

[0707] iv. Rationale for the low SC doses and regimens in the maintenance phase (Dose A)

[0708] High BW, low dose regimen

[0709] The 150 mg SC dose and regimen for participants with >35 kg BW (Table 5; “high BW, low dose” regimen) has been evaluated in the Phase lib study in adults with UC (B7541007 (NCT04090411)). This study explored the efficacy and safety of afimkibart at 50, 150, or 450 mg SC Q4W or placebo during the 12-week induction period and the 40-week maintenance period.

[0710] The 150 mg SC dose in pediatric participants (>35kg) is supported by clinically meaningful efficacy responses and exposure-response trends between 150 mg and 450 mg in the Phase lib studyPATENT

[0711] Attorney Docket No: 50474-373WO3

[0712] Genentech Docket No: P39855-WO-1

[0713] when efficacy data are stratified by individual predicted average drug concentration tertiles. Almost all patients in the 450 mg dose had exposures in the highest tertile, suggesting that the 450 mg dose achieved systemic exposures corresponding to maximal and sustained efficacy over the long term.

[0714] To assess dose (exposure)-response in children with UC, the 150 mg dose is proposed in addition to the 450 mg dose discussed above. It is reasonable to explore a lower maintenance dose in children following the IV induction regimen, when patients have less inflammatory burden, and therefore less risk for suboptimal exposure and / or immunogenicity. In the Phase lib study (B7541007) in adults, the 150 mg and 450 mg doses appeared to have similar ADA profiles, while ADA titers at 50 mg were the highest.

[0715] The proposed SC regimen for pediatric patients is expected to achieve exposure levels that are predicted to be safe and efficacious (parameter: average concentration over 40 weeks (week 14-54)) based on the 150 mg SC Q4W regimen evaluated in the Phase lib UC study in adults. This is illustrated in Figs. 4A and 4B.

[0716] The 50 mg SC dose and regimen for participants with >10 to <35 kg BW (Table 5; “low BW, low dose” regimen) is predicted to achieve exposure levels comparable to those of the 150 mg SC regimen for participants with >35 kg BW (Figs. 4A and 4B).

[0717] Fig. 10 presents the simulated average concentration (Cavg) up to clinical readout (induction treatment phase) for afimkibart in pediatric participants (Cavg, Wk 0-12) and for adult participants with UC (completed studies B7541002 (Phase Ila) and B7541007 (Phase lib); Cavg, Wk 0-14). All IV induction doses in pediatric participants are predicted to provide exposures that have demonstrated efficacy and safety in adult studies. For pediatric participants, simulations were performed using post hoc parameters from adult participants in Studies B7541002 and B7541007 and duplicated randomly by body weight band of 10 kg. For adult participants, simulations were performed using post hoc parameters from Studies B7541002 and B7541007.

[0718] Fig. 11 presents the predicted steady state trough concentration (Ctrough.ss) in the maintenance treatment phase for pediatric participants and for adult participants with UC in Study B7541007 (Phase lib). All SC maintenance doses in pediatric participants are predicted to provide exposures that have demonstrated efficacy and safety in adult studies. For pediatric participants, simulations were performed using post hoc parameters from adult participants in Studies B7541002 and B7541007 and duplicated randomly by body weight band of 10 kg. For adult participants, simulations were performed using post hoc parameters from Studies B7541002 and B7541007.

[0719] v. Rationale for disease worsening criteria and dose intensification

[0720] Starting after the Week 12 assessments and first dose of SC afimkibart, participants who have not improved or have worsened compared with baseline may be eligible for dose intensification to openlabel afimkibart Dose B (450 mg SC Q2W for participants with BW >35 kg, and 150 mg SC Q2W for participants with BW > 10 to <35 kg).

[0721] Predicted maximum concentrations at steady state (Cmax.ss) for pediatric participants are similar to predicted Cmax.ss values for adults at 450 mg SC Q2W, and below simulated Cmax.ss values for adults at 500 mg IV Q2W (Phase Ila trial in UC B7541002) (Fig. 12A).PATENT

[0722] Attorney Docket No: 50474-373WO3

[0723] Genentech Docket No: P39855-WO-1

[0724] The 450 mg SC Q2W regimen for participants with BW > 35 kg, and the 150 mg SC Q2W regimen for participants with BW > 10 to < 35 kg are predicted to achieve similar exposure levels (average concentration over the dosing interval at steady state; Cave) to those predicted for the 450 mg SC Q2W regimen in ongoing Phase III studies in adults with UC, and for the 500 mg IV Q2W regimen in the Phase Ila study in adults with UC (Fig. 12B). For pediatric participants, simulations were performed using post hoc parameters from adult participants in Studies B7541002 and B7541007 and duplicated randomly by body weight band of 10 kg. For adult participants, simulations were performed using post hoc parameters from Studies B7541002 and B7541007.

[0725] vi. Pediatric vs. adult UC

[0726] The inflammatory burden in UC can be more severe in pediatric patients compared to adults, potentially affecting exposure to afimkibart.

[0727] Pediatric patients with UC often present with more extensive disease, such as pancolitis, which involves the entire colon. This is associated with a higher inflammatory burden compared to more limited forms of the disease, such as proctitis or left-sided colitis, which are more common in adults.

[0728] Further, the immune system in children is still maturing, which can lead to a more robust inflammatory response. This heightened immune activity can result in more severe inflammation and symptoms. Pediatric UC can progress more rapidly, leading to a quicker accumulation of inflammatory damage and resulting in more severe clinical presentations and complications.

[0729] Patients with acute severe UC are known to have protein losses through the diseased colon, which partially explains the hypoalbuminemia commonly seen in these patients (Grill et al., J Pediatr Gastroenterol Nutr., 3: 56-61 , 1984). There is increasing recognition that therapeutic mAbs may also pass through the diseased colon mucosa into the stool (Brandse et al., Gastroenterology, 149: 350-355, 2015), affecting the drug's efficacy. In a study of adult patients with moderate-severely active UC, Brandse and colleagues reported that patients without endoscopic response at week 6-8 exhibited higher Day 1 fecal infliximab concentrations, lower serum infliximab levels at week 6, and in some cases, early development of antibodies to infliximab (Brandse et al., Gastroenterology, 146: S-134-134, 2014). Low serum albumin, which may serve as a biomarker for stool protein loss, has been associated with low serum infliximab levels, early infliximab dose escalation, and infliximab non-response in children and adults with UC (Fasanmade, IntJ Clin Pharmacol Then, 48: 297-308, 2010).

[0730] In pediatric patients, particularly those with severe disease or extensive colonic involvement, fecal loss of the therapeutic mAb can be more pronounced compared to adults, which can lead to subtherapeutic serum drug levels and reduced clinical response. This is partly due to the higher inflammatory burden and increased intestinal permeability often seen in pediatric cases.

[0731] Many factors have already been associated with low levels of anti-TNF biologies, poor response, or both in patients with UC (Rosen et al., Aliment Pharmacol Ther, 41 : 1094-1103, 2015). Low serum albumin is the most consistently identified disease factor associated with rapid anti-TNF clearance. With regard to patient factors, weight exhibits a non-linear relationship with anti-TNF clearance such that smaller patients are more likely to exhibit low trough levels with conventional dosing.PATENT

[0732] Attorney Docket No: 50474-373WO3

[0733] Genentech Docket No: P39855-WO-1

[0734] Example 2. A Phase III Randomized Double-Blind Multi-Center Treat-Through Study to Evaluate the Pharmacokinetics, Safety and Efficacy of Induction and Maintenance Therapy with Afimkibart in Children Aged 2-17 Years with Moderately to Severely Active Ulcerative Colitis

[0735] The CA45905 study provided in Examples 1-6 is a Phase III, multicenter, randomized, doubleblind, uncontrolled, treat-through study designed to assess the short-term and long-term efficacy, pharmacokinetics, pharmacodynamics, immunogenicity, safety and tolerability of induction and maintenance therapy with afimkibart (also known as RO7790121 ; formerly PF-06480605 and RVT-3101) in children with moderately to severely active ulcerative colitis (UC). Safe and effective treatments for such patients are a significant unmet medical need. Each of the treatment arms in the study consider a particular dosing regimen of afimkibart.

[0736] The study population includes participants with moderately to severely active UC between the ages of 2 and 17 years who have failed either (i) prior conventional therapy (including aminosalicylates, corticosteroids, and / or immunosuppressants, i.e., “conventional therapy failure”); or (ii) prior advanced therapy including biologies or targeted small molecules (including anti-TNF, anti-IL12 / 23, anti-integrin, S1 P receptor modulators, JAK inhibitors, etc., i.e., “advanced therapy failure”).

[0737] Study schema are provided in Figs. 5B and 5C.

[0738] Example 3. Objectives and Endpoints of the UC Study

[0739] The CA45905 study evaluates the efficacy of afimkibart in inducing and maintaining clinical remission of UC in pediatric patients.

[0740] A. Co-primary objectives and corresponding endpoints

[0741] The co-primary objectives of the CA45905 study are to evaluate the efficacy of afimkibart with respect to clinical remission at Week 12 and Week 52 (see Table 6). This evaluation summarizes the extent to which these outcomes (endpoints) are achieved after treatment with afimkibart (see Table 5) in trial participants from the population of pediatric patients with moderately to severely active UC, as identified by key trial inclusion and exclusion criteria (see Example 5).

[0742] Table 6. Co-Primary Objectives and Endpoints

[0743] <

[0744]

[0745] Clinical remission is defined on the basis of the modified Mayo Score (mMS). mMS and other relevant assessments are described below.

[0746] As noted by the International Council for Harmonisation (ICH) E9(R1), the availability or interpretation of endpoint measurements may be affected by the occurrence of intercurrent events (ICHPATENT

[0747] Attorney Docket No: 50474-373WO3

[0748] Genentech Docket No: P39855-WO-1

[0749] 2020) arising between randomization and endpoint assessment. Strategies to address anticipated intercurrent events are summarized in Table 7.

[0750] Table 7. Strategies for Anticipated Intercurrent Events

[0751]

[0752] Under the above strategies, the estimand supporting each of the co-primary objectives amounts to the proportion of patients from the target population in clinical remission at Week 12 (and Week 52), after a successful course of induction (and maintenance) therapy with afimkibart.

[0753] B. Key secondary objectives and corresponding endpoints

[0754] Efficacy is considered further in key secondary objectives, as described in Table 8. The secondary efficacy objectives target similarly-defined estimands representing a summary outcome (endpoint) measure of afimkibart treatment among pediatric patients with moderately to severely active UC.

[0755] Table 8. Key Secondary Objectives and Endpoints

[0756] > <

[0757] <

[0758] <

[0759] <

[0760]

[0761] PATENT

[0762] Attorney Docket No: 50474-373WO3

[0763] Genentech Docket No: P39855-WO-1

[0764]

[0765] C. Other secondary objectives and corresponding endpoints

[0766] Other secondary objectives examine safety and pharmacokinetics and are described in Table 9, below. Endpoints for these objectives correspond to either a participant-level outcome variable (as with the efficacy endpoints provided in Tables 6 and 8) or a summary of an outcome variable.

[0767] Table 9. Other Secondary Objectives and Endpoints

[0768]

[0769] D. Exploratory objectives and endpoints

[0770] Exploratory objectives and corresponding endpoints of the CA45905 study are described in Table 10, below.

[0771] Table 10. Exploratory Objectives and Endpoints

[0772]

[0773] E. Clinical outcome assessments

[0774] Patient-reported outcome (PRO), observer-reported outcome (ObsRO), and clinician-reported outcome (ClinRO) instruments are completed to assess the treatment benefit of afimkibart. The Week 12 efficacy assessments must be completed prior to the first Week 12 dose of subcutaneous (SC) studyPATENT

[0775] Attorney Docket No: 50474-373WO3

[0776] Genentech Docket No: P39855-WO-1

[0777] treatment in the maintenance phase. PRO / ObsRO data are collected through the instruments summarized in Table 11 and described below.

[0778] Table 11. Patient and Observer-Reported Outcome Instruments

[0779]

[0780] Participants are asked to complete self-administered PROs, where applicable. Participants who meet the age requirements during the screening period are administered the PROs (> 8 years for eDiary stool frequency items and TUMMY-UC); observer-reported eDiary stool frequency and rectal bleeding items and TUMMY-UC are administered to the participant’s parent / legal guardian if they are less than 8 years old at screening. The age-appropriate version of the measure is assigned at screening and used throughout the remainder of the induction and maintenance phases of the study to maintain consistency in SF / RB and TUMMY-UC reporting. At entry to OLE, if a participant has reached the age requirement, participants may begin self-administered PROs. The participant’s parent or legal guardian is to complete the WPAI:UC-Caregiver.

[0781] ClinRO data are collected through the Physician's Global Assessment (PGA), as a component of the Mayo Score. The Pediatric Ulcerative Colitis Activity Index (PUCAI), which is an interviewer administered measure by site staff to assess disease severity based on patient-reported symptoms and activity levels, is collected throughout the study. Additional ClinRO data collected in endoscopic and histologic assessments use the endoscopy component of the (modified) Mayo Score and the Geboes Grading Scale, respectively.

[0782] / . Mayo Score

[0783] Variants of the Mayo Score are evaluated at specified timepoints as a composite based on up to four assessments, described in further detail below: stool frequency subscore (SFS), rectal bleeding subscore (RFS), physician’s global assessment (PGA), and endoscopic subscore (ES). Each of these assessments has scoring that ranges from 0 to 3, with higher values indicating greater severity.

[0784] The composite score variants are defined as follows.

[0785] • Mayo Score (MS): Sum of all four subscores, with range 0-12.

[0786] • Modified Mayo Score (mMS): Sum of SFS, RBS, and ES, with range 0-9.

[0787] • Partial Mayo Score (pMS): Sum of SFS, RBS and PGA, with range 0-9.

[0788] • Partial modified Mayo Score (pmMS): Sum of SFS and RBS, with range 0-6.

[0789] ES is defined to align with the modified version of the scoring system, where the presence of any friability should correspond to a subscore of at least 2.PATENT

[0790] Attorney Docket No: 50474-373WO3

[0791] Genentech Docket No: P39855-WO-1

[0792] / a. Stool Frequency and Rectal Bleeding

[0793] Stool frequency and rectal bleeding are single-item self-reported assessments for individuals aged > 8 years old, both with a 24-hour recall period and scored grading on a 4-point Likert scale. Stool frequency assesses the number of trips to the toilet with a bowel movement or passage of blood and / or mucus, relative to the patient's normal frequency. Rectal bleeding assesses the greatest amount of blood passed per rectum among these trips to the toilet.

[0794] The "normal" reference for stool frequency corresponds to the number of stools in a 24-hour period prior to initial onset of UC signs and symptoms leading to UC diagnosis and when in remission (if the disease has entered remission).

[0795] For participants aged < 8 years old, caregivers complete the stool frequency and rectal bleeding items; those aged > 8 years old self-complete the stool frequency and rectal bleeding items.

[0796] The corresponding subscores (SFS and RBS, respectively) are calculated as an average over 7 days prior to the relevant timepoint.

[0797] SFS is quantified as follows:

[0798] With normal defined at baseline, with respect to each individual participant:

[0799] 0 = Normal number of stools for this patient.

[0800] 1 = 1-2 more stools than normal.

[0801] 2 = 3-4 more stools than normal.

[0802] 3 = 5 or more stools than normal.

[0803] RBS is quantified as follows:

[0804] Representing the worst rectal bleeding observed by the participant that day:

[0805] 0 = No blood seen or no bowel movement.

[0806] 1 = Stool with streaks of blood.

[0807] 2 = Stool with more than streaks of blood.

[0808] 3 = Blood alone passed.

[0809] lb. Physician's Global Assessment

[0810] The subscore reported for Physician’s Global Assessment (PGA) reflects the clinician's assessment of the participant's current overall status, acknowledging criteria including the participant’s daily abdominal discomfort, general sense of well-being, physical examination findings and performance status (Schroeder et al., N Engl J Med., 317: 1625-1629, 1987). PGA considers the following: stool frequency, rectal bleeding, other participant-reported signs and symptoms, locally-read endoscopy, clinician observations, physical examination, and other pertinent findings.

[0811] PGA is quantified as follows:

[0812] 0 = Normal.

[0813] 1 = Mild.

[0814] 2 = Moderate.

[0815] 3 = Severe.PATENT

[0816] Attorney Docket No: 50474-373WO3

[0817] Genentech Docket No: P39855-WO-1

[0818] ic. Endoscopy

[0819] Endoscopy subscore (ES) should reflect the worst appearance of the mucosa on flexible sigmoidoscopy or colonoscopy, on a 4-point scale. Consistent with regulatory guidance, this scale excludes mild friability from the features characteristic of ES = 1 ; any friability apparent on the video recording should be reported as ES s 2. ES evaluated by blinded central reading is used to determine inclusion criteria, efficacy endpoints, and disease worsening criteria.

[0820] Biopsies are collected during withdrawal of the endoscope from the bowel.

[0821] ES is quantified as follows:

[0822] 0 = Normal appearance of mucosa.

[0823] 1 = Mild disease (erythema, decreased vascular pattern, no friability).

[0824] 2 = Moderate disease (marked erythema, absent vascular pattern, friability, erosions). 3 = Severe disease (spontaneous bleeding, ulceration).

[0825] / / . PUCAI

[0826] The Pediatric Ulcerative Colitis Activity Index (PUCAI) assesses disease activity in pediatric UC patients (Turner et al., Gastroenterology, 133: 423-432, 2007). The measure is interviewer-administered and includes 6 items relating to abdominal pain, rectal bleeding, stool consistency, frequency, nocturnal stools and assessment of activity limitations based on patient report. The instructions advise that answers should reflect a daily average of the last 2 days, but that the most recent 24 hours should be considered if clinical conditions are changing. For patients undergoing colonoscopy, answers should reflect the 2 days before bowel clean out was started. The items are scored on a 3- or 4-point Likert scale, and a global score can be generated with a higher score indicating more severe disease activity. The measure has been found to be valid, reliable, and responsive in pediatric UC patients (Turner et al., Gastroenterology, 133: 423-432, 2007).

[0827] Hi. Geboes Grading Scale

[0828] The Geboes Grading Scale is a seven-item classification system to evaluate histological activity in UC, with items graded from least to most severe features of inflammation (Geboes et al., Gut,

[0829]

[0830] 404-409, 2000). Each grade is assigned a subgrade ranging from 0 to 3 or 4, with higher values associated with greater severity of the corresponding features.

[0831] Grading will be carried out by central reading, using slide images processed from colonic biopsies taken during endoscopy at specified visits.

[0832] iv. TUMMY-UC

[0833] The TUMMY-UC is an outcome measure used to assess disease-related symptoms in pediatric UC (Marcovitch et al., Gastroenterology, 164: 610-618, 2023). The measure contains 8 items and is patient-reported by participants aged > 8 years old and observer-reported by caregivers of children aged 2-7 years old. The TUMMY-UC assesses abdominal pain, stool frequency and consistency, amount and frequency of blood in stool, urgency, weakness and nocturnal stool in the last 24 hours. The items are scored on a 4-, 5-, or 6-point Likert scale depending on the question, and a total score can be generatedPATENT

[0834] Attorney Docket No: 50474-373WO3

[0835] Genentech Docket No: P39855-WO-1

[0836] with a higher score indicating worse symptoms. The measure has been found to be valid, reliable, and responsive in pediatric UC patients (Marcovitch et al., Gastroenterology, 164: 610-618, 2023).

[0837] v. WPAI:UC- Caregiver

[0838] The Work Productivity and Activity Impairment Questionnaire: Ulcerative Colitis- Caregiver Questionnaire (WPAI:UC- Caregiver) v2.0 is an adaptation of the WPAI: Specific Health Profile, a generic patient-reported measure of absenteeism, presenteeism, work productivity and activity impairment over the past seven days (Reilly et al., Pharmacoeconomics, 4: 353-365, 1993).

[0839] All respondents are then asked to indicate the impact of their child’s UC on regular daily activities using a 0-10 NRS (Q6). Four scores (absenteeism, presenteeism, work productivity, and activity impairment) are obtained from the scale and are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity (i.e., worse outcomes).

[0840] Example 4. UC Study Design

[0841] A. Overall design

[0842] The CA45905 study has a treat-through design that consists of a screening period of up to 35 days (+ 7 days) to determine eligibility; a 12-week induction treatment phase; a 40-week maintenance treatment phase; an optional open-label extension (OLE) treatment phase; and a safety follow-up period of 12 weeks (consisting of two visits, one at 6 weeks and one at 12 weeks following the final dose of study treatment).

[0843] Approximately 75 sites globally participate to enroll approximately 100 participants with moderately to severely active UC between the ages of 2 and 17 years who have failed either: (i) prior conventional therapy (including aminosalicylates, corticosteroids and / or immunosuppressants, i.e., “conventional therapy failure”); or (ii) prior advanced therapy (including biologies or targeted small molecules such as anti-tumor necrosis factor (TNF), anti-IL12 / 23, anti-integrin, sphingosine-1 -phosphate (S1 P) receptor modulators, and Janus kinase (JAK) inhibitors), i.e., “advanced therapy failure.” Complete definitions of the terms “conventional therapy failure” and “advanced therapy failure” can be found in Example 5, below. Entry criteria are based on confirmation of moderately to severely active UC during screening, defined as a modified Mayo Score (mMS) of 5 to 9, including an endoscopic subscore (ES) of 2 or 3, as confirmed by a centrally-read endoscopy (flexible sigmoidoscopy or colonoscopy).

[0844] Eligible study participants are randomly assigned one of two doses within their body weight group:

[0845] High body weight (> 35 kg) groups:

[0846] Group 1 (Dose A): afimkibart: a 250 mg dose administered intravenously (IV) at Weeks 0, 2, 6 and 10 followed by a 150 mg dose administered subcutaneously (SC) every four weeks (Q4W) from Week 12 through Week 52.

[0847] Group 2 (Dose B): afimkibart: a 500 mg dose administered IV at Weeks 0, 2, 6 and 10 followed by a 450 mg dose administered SC every four weeks (Q4W) from Week 12 through Week 52.PATENT

[0848] Attorney Docket No: 50474-373WO3

[0849] Genentech Docket No: P39855-WO-1

[0850] Low body weight (> 10 kg to < 35 kg) groups:

[0851] Group 3 (Dose A): afimkibart: an 8 mg / kg dose (not exceeding 250 mg) administered IV at Weeks 0, 2, 6 and 10 followed by a 50 mg dose administered SC every four weeks (Q4W) from Week 12 through Week 52.

[0852] Group 4 (Dose B): afimkibart: a 16 mg / kg dose (not exceeding 500 mg) administered IV at Weeks 0, 2, 6 and 10 followed by a 150 mg dose administered SC every four weeks (Q4W) from Week 12 through Week 52.

[0853] Cohort 1 of the study is an open-label interim PK analysis of the first 10 patients recruited in both high and low body weight groups. The high body weight groups (Group 1 and Group 2) are randomized according to a 1 :1 ratio to one of two doses of afimkibart (Dose A or Dose B); all low body weight participants in Cohort 1 of the study are assigned to Dose A (low dose, with a minimum of 3 participants in Group 3).

[0854] Dosing in Cohort 2 is fully double-blind. Participants in Cohort 2 are randomized according to a 1 :1 ratio to either Dose A or Dose B of afimkibart (Figs. 5B and 5C), stratified by the following factors:

[0855] • Baseline body weight (< 35 kg I > 35 kg).

[0856] • Prior advanced therapy treatment at baseline (yes I no).

[0857] Study schema are provided in Figs. 5B and 5C.

[0858] The induction phase (IV dosing at Weeks 0, 2, 6 and 10) evaluates the induction of clinical remission, measured at Week 12.

[0859] After completion of the induction phase, participants continue with the administration of afimkibart SC during the maintenance phase (Weeks 12-52), where the durability of clinical response and remission are examined. Afimkibart is administered subcutaneously (SC) Q4W from Week 12 through Week 52.

[0860] From Week 12 onwards, participants who have completed Week 12 assessments are eligible to dose intensify to open-label afimkibart given every two weeks (Q2W) at Dose B (150 mg for low body weight participants and 450 mg for high body weight participants) for a period of 12 weeks, provided their clinical condition meets the disease worsening criteria described below. These participants then remain on open-label afimkibart at Dose B at Q4W intervals for the remainder of the maintenance phase (until the Week 52 visit). Additionally, if participants do not meet the response criteria at Week 52, or they meet the disease worsening criteria during the OLE, they are to dose intensify to Q2W at Dose B for a period of 12 weeks, after which they will de-intensify to Q4W at Dose B.

[0861] The aim of the study is to assess the safety, efficacy, and pharmacokinetics of afimkibart in children with UC. Efficacy is assessed by the co-primary endpoints of clinical remission at Week 12 (induction) and Week 52 (maintenance); see Table 6. Clinical remission is defined by a modified Mayo Score (mMS) < 2 with rectal bleeding score (RBS) of 0, stool frequency score (SFS) of 0 or 1 , and endoscopic score (ES) of 0 or 1.

[0862] Secondary endpoints include the proportion of participants achieving pediatric ulcerative colitis activity index (PUCAI) response as defined by reduction in baseline PUCAI by > 20 points at each of Week 12 and Week 52, and PUCAI remission (as defined by PUCAI < 10 points) at each of Week 12 and 52 (see Tables 8 and 9).PATENT

[0863] Attorney Docket No: 50474-373WO3

[0864] Genentech Docket No: P39855-WO-1

[0865] B. Disease worsening criteria and dose intensification

[0866] Starting after the Week 12 assessments and the first dose of SC study drug, participants who have not improved or have worsened compared with Baseline (Day 1 of Week 0), may be eligible for dose intensification to open-label afimkibart at Dose B (450 mg SC Q2W for participants with BW >35 kg, and 150 mg SC Q2W for participants with BW > 10 to <35 kg). In order to be eligible for dose intensification, participants must meet all of the following three criteria:

[0867] 1. Daily rectal bleeding rating > 2 on at least three of the past seven days, excluding any days coinciding with bowel preparation, endoscopy, and the day after endoscopy.

[0868] 2. ES > 2 per a centrally-read endoscopy conducted within the past 6 weeks. If the Week 12 endoscopic assessment has been performed in the past 6 weeks, the results of this endoscopy must be used in the evaluation of the disease worsening criteria. Otherwise, the endoscopy may be repeated. If a repeat endoscopy cannot be performed, then one of the following criteria may be used: (i) fecal calprotectin > 250 pg / g based on stool sample collection in the past 4 weeks, or (ii) bowel wall thickness > 2.5 mm per abdominal ultrasound conducted in the past 6 weeks.

[0869] AND

[0870] 3. Potential for differential diagnoses, such as presence of enteric infection, has been ruled out.

[0871] This should be confirmed by stool culture (e.g., an ova and parasite evaluation) including C. difficile testing. If cytomegalovirus (CMV) infection is suspected, a tissue biopsy should be performed.

[0872] Participants continue the intensified Q2W SC dosing schedule for a period of 12 weeks. After completing this 12-week Q2W dosing period, participants receive open-label afimkibart at Dose B Q4W SC for the remainder of the maintenance period (up to Week 52). If the 12-week dosing period extends beyond Week 52 of the maintenance phase, participants may complete the remainder of the 12-week dose intensification in the OLE phase.

[0873] Participants who have entered the open-label extension phase through completion of the entire 52-week study without meeting disease worsening criteria may also be eligible for dose intensification to open-label afimkibart at Dose B Q2W SC if they meet the disease worsening criteria outlined above.

[0874] C. Open-label extension phase

[0875] All participants have the opportunity to participate in the optional OLE phase of the study with access to afimkibart and monitoring, provided they meet specified eligibility criteria.

[0876] Participants may be eligible to enter OLE after completion of the 40-week maintenance phase and upon completion of the Week 52 assessments. The first OLE visit for participants entering from the maintenance phase is at Week 56, and participants continue in the OLE phase on the Q4W dose regimen (150 mg for low body weight or 450 mg for high body weight SC Q4W).

[0877] Participants at Week 52 who do meet response criteria (i.e., are not in clinical remission defined as mMS < 2 with SFS < 0 or 1 , RBS = 0, and ES < 0 or 1) and are not on open-label afimkibart enter thePATENT

[0878] Attorney Docket No: 50474-373WO3

[0879] Genentech Docket No: P39855-WO-1

[0880] OLE at Q2W closing frequency. Participants may also be eligible to dose-intensity for 12 weeks to Q2W dose B regimen if they meet disease worsening criteria (DWO) during OLE and have not previously met DWC throughout the study.

[0881] The total duration of study participation for an individual is expected to be approximately 18 months without OLE participation. With OLE participation, treatment continues for up to approximately an additional 4 years.

[0882] D. Selection of study population

[0883] The CA45905 study assesses afimkibart in participants between 2 and 17 years of age. The eligibility criteria for this study limit enrollment to participants aged > 2 years to < 18 years old, with moderately to severely active UC disease, as confirmed by a modified Mayo Score (mMS) of 5-9 and an endoscopic subscore (ES) of at least 2.

[0884] E. End of study definition and duration of participation

[0885] The end of the study is defined as the date of the last visit of the last participant in the study or the date when the last data point required for statistical analysis, safety follow-up, or statistical analysis follow-up is received from the last participant, whichever occurs later. The end of the study is expected to occur approximately 18 months after the last participant is enrolled, unless at least one participant enters the OLE phase.

[0886] Example 5. UC Study Population

[0887] Approximately 100 pediatric participants with ulcerative colitis (UC) are enrolled in the CA45905 study. Inclusion and exclusion criteria are provided below.

[0888] A. Inclusion criteria

[0889] Potential participants are eligible for inclusion in the study only if all of the following criteria apply:

[0890] / . General inclusion criteria

[0891] • Age > 2 and < 18 years. Participants must be <18 years old at the time of signing the informed consent form (ICF) / assent form to be eligible to enroll in the study. If a participant turns 18 years old at any time after signing the ICF / assent form they should continue in the study.

[0892] • Body weight > 10 kg.

[0893] / / . UC-specific inclusion criteria

[0894] • Participant has had a confirmed diagnosis of UC with supportive clinical, endoscopic and histopathological evidence.

[0895] • Active UC confirmed by endoscopy (flexible sigmoidoscopy or colonoscopy).

[0896] • Moderately to severely active UC defined as a modified Mayo Score (mMS) of 5 to 9 points, including a Mayo endoscopic score (ES) of 2 or 3, confirmed through centrally read endoscopy performed either: (i) during the screening period; or (ii) before the screening period (independently of the study, for standard-PATENT

[0897] Attorney Docket No: 50474-373WO3

[0898] Genentech Docket No: P39855-WO-1

[0899] of-care), within 4 weeks of randomization, and in patients who already have an established UC diagnosis. Participants must not have had any new UC-related medications initiated between the standard-of-care (SOC) endoscopy and randomization. All UC-related concomitant medications must have been stabilized prior to SOC endoscopy.

[0900] Hi. Reproductive inclusion criteria

[0901] • For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use an acceptable method of contraception and agreement to refrain from egg donation or undergoing fertility treatment during the treatment period and for 95 days after the final dose of afimkibart.

[0902] iv. Prior medications inclusion criteria

[0903] • Participants must have had at least one of the treatments provided below in the past with inadequate response, loss of response, and / or intolerance (e.g., a conventional therapy failure or an advanced therapy failure)

[0904] Inadequate response is defined as having signs and symptoms of persistently active disease despite completing at least the approved dosing regimen in the product label for medications approved for pediatric UC. For medications not approved for pediatric UC (“off-label” or investigational), the definition of inadequate response is at the discretion of the investigator; however, for advanced therapies the extent of exposure should include at least an induction regimen commensurate with the corresponding adult label.

[0905] Intolerance may include, but is not limited to, infusion-related reactions, injection site reactions, rash, serum sickness, hepatic abnormalities, demyelination, congestive heart failure, and infections. There is no minimum requirement for dose or duration if a potential participant was determined to be intolerant to prior treatment.

[0906] Loss of response is defined as the recurrence of signs and symptoms of active disease during approved treatment following prior clinical benefit (discontinuation despite clinical benefit does not qualify as having failed or being intolerant to UC advanced therapy).

[0907] The medication used to qualify the participant for entry into this category must be approved for the treatment of UC (in either adults or children), including biosimilars. Participants previously exposed to investigational therapies for the treatment of UC must still meet the inclusion criteria "Conventional Therapy Failure" or "Advanced Therapy Failure", below.

[0908] Conventional Therapy Failure

[0909] • Steroids (e.g., systemic prednisone, oral budesonide).

[0910] The following definitions are used as guidelines for the use of corticosteroids in this trial:

[0911] o Corticosteroid refractory: Persistent active disease despite treatment with at least one 4-week induction regimen, including a starting dose of > 1.0 mg / kg / day or > 40 mg / day of prednisone (or equivalent, whichever is lower) for at least 2 weeks or IV prednisone for > 5 days, or persistentlyPATENT

[0912] Attorney Docket No: 50474-373WO3

[0913] Genentech Docket No: P39855-WO-1

[0914] active disease after at least 4 weeks of oral budesonide given 9 mg / day or 0.45 mg / kg / day, whichever is lower.

[0915] o Corticosteroid dependent: (i) Unable to reduce steroids below the equivalent of prednisone 10 mg / day within 3 months of starting steroids, without recurrent active disease, or (ii) relapse within 3 months of stopping steroids.

[0916] o Corticosteroid intolerant: History of intolerance to corticosteroids (including but not limited to Cushing syndrome, osteopenia / osteoporosis, hyperglycemia, insomnia, infection).

[0917] • At least 12 weeks of an immunomodulator, which can include:

[0918] o > 1.5 mg / kg / day of oral azathioprine (AZA) (or per local standard of care).

[0919] o > 0.75 mg / kg / day of oral 6-mercaptopurine (6-MP) (or per local standard of care).

[0920] o > 10 mg / m2(up to 25 mg) weekly intramuscular or SC methotrexate (MTX).

[0921] o Persistent signs and symptoms of active disease despite a 6-thioguanine (6-TG) level of > 200 pmol / 8 x 108RBCs during at least one 12-week regimen of oral AZA or 6-MP at a stable or increasing dose.

[0922] o History of intolerance to AZA, 6-MP, or MTX (including, but not limited to, nausea / vomiting, abdominal pain, pancreatitis, LFT abnormalities, lymphopenia, TPMT genetic mutation, infection).

[0923] • At least 4 weeks of an oral aminosalicylate, which can include a minimum dose of the following:

[0924] o 1.2 g / day of mesalamine (or per local standard of care).

[0925] o 30 mg / kg / day up to 4.0 g / day of sulfasalazine (or per local standard of care).

[0926] o 1.0 g / day of olsalazine (or per local standard of care).

[0927] o 2.25 g / day of balsalazide (or per local standard of care).

[0928] • The conventional therapy failure population also includes patients who have received advanced therapy (biologies or small molecules) in the past but stopped therapy based on reasons other than failure (e.g., change in reimbursement coverage, well-controlled disease).

[0929] Advanced Therapy Failure

[0930] The medications used to qualify the participant for entry into this category include the following therapies (and any relevant biosimilars) approved for the treatment of adult or pediatric UC. This approval need not be local.

[0931] • Anti-tumor necrosis factor (TNF) agents, including and not limited to the following:

[0932] o At least one 6-week induction regimen of infliximab (> 5 mg / kg IV at 0, 2, and 6 weeks or per local label) or equivalent biosimilar.

[0933] o At least one 4-week induction regimen of adalimumab (body weight > 40 kg: one 160 mg SC dose followed by one 80 mg SC dose followed by one 40 mg SC dose at least 2 weeks apart or per local label; body weight > 17 kg to < 40 kg: one 80 mg dose followed by one 40 mg dose and one 20 mg dose at least 2 weeks apart) or equivalent biosimilar.

[0934] • Anti-integrins including vedolizumab.

[0935] • Anti-IL12 / IL23 including ustekinumab, mirikizumab, risankizumab, guselkumab.

[0936] • Janus kinase (JAK) inhibitors including upadacitinib, tofacitinib.

[0937] • Sphingosine-1 -phosphate (S1P) receptor modulators including ozanimod and etrasimod.PATENT

[0938] Attorney Docket No: 50474-373WO3

[0939] Genentech Docket No: P39855-WO-1

[0940] B. Exclusion criteria

[0941] Potential participants are excluded from the study if any of the following criteria apply:

[0942] / . IBD exclusion criteria

[0943] • Monogenic disorder pertaining to infant onset inflammatory bowel disease (IBD).

[0944] • Severe UC as evidenced by any of the following:

[0945] - Hospitalization for the treatment of acute severe UC (defined as a Pediatric Ulcerative Colitis Activity Index (PUCAI) score of 65 or greater) < 2 weeks prior to screening or, in the physician's judgement, is likely to require surgical intervention of any kind for UC (e.g., colectomy) during the study. Hospitalizations required for colonoscopy or for management of mild to moderate UC are not exclusionary.

[0946] - Current evidence of fulminant colitis, toxic megacolon, or recent history (within 6 months) of toxic megacolon, or bowel perforation.

[0947] - Prior extensive colonic resection, subtotal, or total colectomy, or planned surgery for UC during the study.

[0948] • Current diagnosis of Crohn's disease (CD), abdominal / intrabdominal / perianal fistula and / or abscess, indeterminant colitis, IBD-unclassified, microscopic colitis, ischemic colitis, infectious colitis, radiation colitis, or active diverticular disease.

[0949] • Presence of an ostomy or ileoanal pouch.

[0950] • Current diagnosis or suspicion of primary sclerosing cholangitis.

[0951] / / . Medical history exclusion criteria

[0952] • Poor peripheral venous access.

[0953] • Any major surgery within 6 weeks prior to screening or a major planned surgery during the study.

[0954] • Significant uncontrolled medical comorbidity (such as cardiac, pulmonary, renal, hepatic, endocrine, or gastrointestinal disorders (excluding UC)), psychiatric, or other condition that would confound the study results, compromise participant safety, or compliance with trial procedures.

[0955] • Pregnant or breastfeeding, or intention of becoming pregnant during the study or within 95 days after the final dose of afimkibart.

[0956] • Participants of childbearing potential must have a negative serum pregnancy test result at screening and a negative urine pregnancy test on Day 1 prior to initiation of study treatment.

[0957] • Any condition precluding endoscopic evaluation.

[0958] • Any past or current evidence of cancer of the gastrointestinal tract, definite low-grade or high-grade colonic dysplasia. Adenomas that are not completely removed are exclusionary. Once completely removed, the participant may be eligible for the study.

[0959] • History of malignancy within 5 years prior to screening visit.

[0960] • History of alcohol, drug, or chemical abuse < 1 year prior to screening endoscopy.

[0961] • History of blood transfusion within 30 days prior to screening endoscopy or between screening endoscopy and randomization.PATENT

[0962] Attorney Docket No: 50474-373WO3

[0963] Genentech Docket No: P39855-WO-1

[0964] Hi. Infection or infection risk exclusion criteria

[0965] • Any clinically significant infection < 4 weeks prior to randomization that has not resolved, and / or that required hospitalization and / or IV antibiotics. Any clinically significant infection that was opportunistic in nature is not permitted within 3 months prior to randomization.

[0966] • Evidence of, or treatment for, Clostridioides difficile (C. difficile; formerly known as Clostridium difficile) as assessed by detection of C. difficile toxin within 30 days prior to randomization (Day 1) or other enteric pathogens (as assessed by stool culture / sensitivity and ova and parasite evaluation) within 30 days prior to randomization (Day 1).

[0967] • Any diagnosis of cytomegalovirus (CMV) colitis in the past 30 days prior to randomization (including diagnosis during screening). Laboratory confirmation of CMV from a colon biopsy sample (e.g. tissue immunohistochemistry or tissue PCR, as per local standards) is required during screening evaluation only if clinical suspicion is high and to determine the need for CMV treatment.

[0968] • Confirmation of HIV infection (e.g. positive HIV test) at screening.

[0969] • Positive test results for hepatitis B infection at screening, defined as meeting either of the following criteria: (i) positi...

Claims

PATENTAttorney Docket No: 50474-373WO3Genentech Docket No: P39855-WO-1WHAT IS CLAIMED IS:

1. A method of treating an inflammatory bowel disease (IBD) in a pediatric patient, the method comprising administering to the patient an effective amount of an anti-TNF-like ligand 1 A (TL1 A) antibody in a dosing regimen comprising an induction phase, wherein the induction phase comprises administration of only four doses of the anti-TL1 A antibody, wherein:(i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose;(ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and(iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose,wherein the anti-TL1 A antibody comprises the following complementarity-determining regions (CDRs):(a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3;(b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4;(c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5;(d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6;(e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and(f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

2. A method of treating an IBD in a pediatric patient, the method comprising administering to the patient an effective amount of an anti-TL1 A antibody in a dosing regimen comprising an induction phase and a maintenance phase, wherein:(a) the induction phase comprises administration of only four doses of the anti-TL1 A antibody, wherein:(i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose;(ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and(iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and(b) the maintenance phase comprises administration of the anti-TL1 A antibody every four weeks, wherein the anti-TL1 A antibody comprises the following CDRs:(a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3;(b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4;(c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5;(d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6;(e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and(f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.PATENTAttorney Docket No: 50474-373WO3Genentech Docket No: P39855-WO-13. The method of claim 1 or 2, wherein, in the induction phase, the anti-TL1 A antibody is administered intravenously at a dose of between 8 mg / kg and 16 mg / kg, and wherein the dose does not exceed 500 mg.

4. The method of claim 1 or 2, wherein the patient has a body weight of at least 10 kg and less than 35 kg and, in the induction phase, the anti-TL1 A antibody is administered intravenously at a dose of about 16 mg / kg, wherein the dose does not exceed 500 mg.

5. The method of claim 1 or 2, wherein the patient has a body weight of at least 10 kg and less than 35 kg and, in the induction phase, the anti-TL1 A antibody is administered intravenously at a dose of about 8 mg / kg, wherein the dose does not exceed 250 mg.

6. The method of claim 1 or 2, wherein the patient has a body weight of at least 35 kg and, in the induction phase, the anti-TL1 A antibody is administered intravenously at a dose of about 500 mg.

7. The method of claim 1 or 2, wherein the patient has a body weight of at least 35 kg and, in the induction phase, the anti-TL1 A antibody is administered intravenously at a dose of about 250 mg.

8. The method of any one of claims 1-7, wherein the induction phase has a duration of about 12 weeks.

9. The method of claim 8, wherein:(a) the first dose of the anti-TL1 A antibody is administered on about Day 1 of Week 0;(b) the second dose of the anti-TL1 A antibody is administered on about Day 1 of Week 2;(c) the third dose of the anti-TL1 A antibody is administered on about Day 1 of Week 6; and(d) the fourth dose of the anti-TL1 A antibody is administered on about Day 1 of Week 10.

10. The method of any one of claims 1 and 3-9, wherein the dosing regimen further comprises a maintenance phase.11 . The method of any one of claims 2-10, wherein, in the maintenance phase, the anti-TL1 A antibody is administered subcutaneously at a dose of between 50 mg and 450 mg.

12. The method of any one of claims 1 -4 and 8-11 , wherein the patient has a body weight of at least 10 kg and less than 35 kg and, in the maintenance phase, the anti-TL1 A antibody is administered subcutaneously at a dose of about 150 mg.PATENTAttorney Docket No: 50474-373WO3Genentech Docket No: P39855-WO-113. The method of any one of claims 2, 3, 5, and 8-11 , wherein the patient has a body weight of at least 10 kg and less than 35 kg and, in the maintenance phase, the anti-TL1 A antibody is administered subcutaneously at a dose of about 50 mg.

14. The method of any one of claims 2, 3, 6, and 8-11 , wherein the patient has a body weight of at least 35 kg and, in the maintenance phase, the anti-TL1 A antibody is administered subcutaneously at a dose of about 450 mg.

15. The method of any one of claims 2, 3, and 7-11 , wherein the patient has a body weight of at least 35 kg and, in the maintenance phase, the anti-TL1 A antibody is administered subcutaneously at a dose of about 150 mg.

16. The method of any one of claims 2-15, wherein the maintenance phase comprises at least two doses of the anti-TL1 A antibody.

17. The method of claim 16, wherein the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks.

18. The method of claim 16 or 17, wherein the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every two weeks.

19. The method of any one of claims 16-18, wherein the maintenance phase 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-TL1 A antibody is administered every two weeks.

20. The method of claim 18 or 19, wherein:(i) the patient has a body weight of at least 10 kg and less than 35 kg and, in the at least one interval in which the anti-TL1 A antibody is administered every two weeks, the anti-TL1 A antibody is administered subcutaneously at a dose of about 150 mg; or(ii) the patient has a body weight of at least 35 kg and, in the at least one interval in which the anti-TL1 A antibody is administered every two weeks, the anti-TL1 A antibody is administered subcutaneously at a dose of about 450 mg.21 . The method of any one of claims 2-20, wherein the maintenance phase comprises eleven doses of the anti-TL1 A antibody.

22. The method of any one of claims 2-21 , wherein the maintenance phase has a duration of about 40 weeks.PATENTAttorney Docket No: 50474-373WO3Genentech Docket No: P39855-WO-123. The method of any one of claims 1-22, wherein a corticosteroid is administered to the patient in the induction phase, and the dose of the corticosteroid is tapered during the induction phase.

24. The method of claim 23, wherein administration of the corticosteroid is discontinued during the dosing regimen.

25. The method of claim 23 or 24, wherein the corticosteroid is prednisone or an equivalent thereof, budesonide, or budesonide multi-matrix (MMX).

26. The method of any one of claims 2-25, wherein the first dose of the maintenance phase is administered about two weeks after administration of the fourth dose of the induction phase.

27. The method of any one of claims 2-26, wherein the dosing regimen has a duration of about 52 weeks.

28. The method of claim 27, wherein:(a) the first dose of the induction phase is administered on about Day 1 of Week 0;(b) the second dose of the induction phase is administered on about Day 1 of Week 2;(c) the third dose of the induction phase is administered on about Day 1 of Week 6;(d) the fourth dose of the induction phase is administered on about Day 1 of Week 10;(e) the first dose of the maintenance phase is administered on about Day 1 of Week 12; and (f) the subsequent doses of the maintenance phase are administered on about Day 1 of Weeks 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52.

29. The method of any one of claims 1-28, wherein the dosing regimen further comprises an extension phase comprising administration of one or more additional dosing cycles of the anti-TL1 A antibody.

30. The method of claim 29, wherein:(a) the extension phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks;(b) the extension phase comprises subcutaneous administration of the anti-TL1 A antibody every two weeks; or(c) the extension phase comprises (i) at least one interval in which the anti-TL1 A antibody is administered every four weeks and (ii) at least one interval in which the anti-TL1 A antibody is administered every two weeks.31 . The method of claim 29 or 30, wherein the one or more dosing cycles of the extension phase are administered to the patient following disease worsening during the maintenance phase.PATENTAttorney Docket No: 50474-373WO3Genentech Docket No: P39855-WO-132. The method of claim 30 or 31 , wherein:(i) the patient has a body weight of at least 10 kg and less than 35 kg and, in the at least one interval in which the anti-TL1 A antibody is administered every two weeks, the anti-TL1 A antibody is administered subcutaneously at a dose of about 150 mg; or(ii) the patient has a body weight of at least 35 kg and, in the at least one interval in which the anti-TL1 A antibody is administered every two weeks, the anti-TL1 A antibody is administered subcutaneously at a dose of about 450 mg.

33. The method of any one of claims 1-32, wherein the IBD is ulcerative colitis (UC).

34. The method of claim 33, wherein the UC is moderately to severely active ulcerative colitis.

35. The method of claim 33 or 34, wherein the patient has a modified Mayo score (mMS) of between 5 points and 9 points.

36. The method of any one of claims 33-35, wherein the patient has a Mayo endoscopic score (ES) of 2 or 3.

37. The method of any one of claims 1-32, wherein the IBD is Crohn’s disease (CD).

38. The method of claim 37, wherein the CD is moderately to severely active CD.

39. The method of claim 37 or 38, wherein:(a) the patient has a Simple Endoscopic Score for Crohn’s Disease (SES-CD) of equal to or greater than 6; or(b) the patient has isolated ileal disease only, and has an SES-CD of equal to or greater than 4.

40. The method of any one of claims 37-39, wherein the patient has a pediatric Crohn’s disease activity index (PCDAI) that is at least 30.

41. The method of any one of claims 33-40, wherein the patient has previously been treated with a therapy for UC or CD and has experienced inadequate response to the therapy, loss of response to the therapy, and / or intolerance of the therapy.

42. The method of claim 41 , wherein the therapy was a conventional therapy.

43. The method of claim 42, wherein the conventional therapy comprised administration of a steroid, an immunomodulator, or an oral aminosalicylate.

44. The method of claim 41 , wherein the therapy was an advanced therapy.PATENTAttorney Docket No: 50474-373WO3Genentech Docket No: P39855-WO-145. The method of claim 44, wherein the advanced therapy comprised administration of an anti-tumor necrosis factor (TNF) agent, an anti-integrin agent, an anti-IL12 / IL23 agent, a Janus kinase (JAK) inhibitor, or a sphingosine-1 -phosphate (S1 P) inhibitor.

46. A method of treating UC in a pediatric patient having a body weight of at least 10 kg and less than 35 kg, the method comprising administering to the patient an effective amount of an anti-TL1 A antibody in a dosing regimen comprising an induction phase and a maintenance phase, wherein:(a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 16 mg / kg, wherein the dose does not exceed 500 mg, wherein:(i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose;(ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and(iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and(b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks at a dose of about 150 mg,wherein the anti-TL1 A antibody comprises the following CDRs:(a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3;(b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4;(c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5;(d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6;(e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and(f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

47. A method of treating UC in a pediatric patient having a body weight of at least 10 kg and less than 35 kg, the method comprising administering to the patient an effective amount of an anti-TL1 A antibody in a dosing regimen comprising an induction phase and a maintenance phase, wherein:(a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 8 mg / kg, wherein the dose does not exceed 250 mg, wherein:(i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose;(ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and(iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and(b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks at a dose of about 50 mg,wherein the anti-TL1 A antibody comprises the following CDRs:PATENTAttorney Docket No: 50474-373WO3Genentech Docket No: P39855-WO-1(a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3;(b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4;(c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5;(d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6;(e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and(f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

48. A method of treating UC in a pediatric patient having a body weight of at least 35 kg, the method comprising administering to the patient an effective amount of an anti-TL1 A antibody in a dosing regimen comprising an induction phase and a maintenance phase, wherein:(a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 500 mg, wherein:(i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose;(ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and(iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and(b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks at a dose of about 450 mg,wherein the anti-TL1 A antibody comprises the following CDRs:(a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3;(b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4;(c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5;(d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6;(e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and(f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

49. A method of treating UC in a pediatric patient having a body weight of at least 35 kg, the method comprising administering to the patient an effective amount of an anti-TL1 A antibody in a dosing regimen comprising an induction phase and a maintenance phase, wherein:(a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 250 mg, wherein:(i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose;(ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and(iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; andPATENTAttorney Docket No: 50474-373WO3Genentech Docket No: P39855-WO-1(b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks at a dose of about 150 mg,wherein the anti-TL1 A antibody comprises the following CDRs:(a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3;(b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4;(c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5;(d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6;(e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and(f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

50. The method of any one of claims 1-36 and 41-49, wherein, in a population of patients treated according to the method, the treating results in an increase in the proportion of patients who have achieved clinical remission at the end of the induction phase as compared to a reference population.51 . The method of claim 50, wherein the induction phase has a duration of about 12 weeks, and the treating results in an increase in the proportion of patients who have achieved clinical remission at Week 12.

52. The method of any one of claims 1-32 and 41-49, wherein, in a population of patients treated according to the method, the treating results in an increase in the proportion of patients who have achieved clinical remission at the end of the maintenance phase as compared to a reference population.

53. The method of claim 52, wherein the dosing regimen has a duration of about 52 weeks, and the treating results in an increase in the proportion of patients who have achieved clinical remission at Week 52.

54. The method of any one of claims 50-53, wherein clinical remission is a modified Mayo Score (mMS) <2 with rectal bleeding score (RBS) of 0, stool frequency subscore (SFS) = 0 or 1 , and endoscopic subscore (ES) = 0 or 1 .

55. A method of treating CD in a pediatric patient having a body weight of at least 10 kg and less than 35 kg, the method comprising administering to the patient an effective amount of an anti-TL1 A antibody in a dosing regimen comprising an induction phase and a maintenance phase, wherein:(a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 16 mg / kg, wherein the dose does not exceed 500 mg, wherein:(i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose;(ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; andPATENTAttorney Docket No: 50474-373WO3Genentech Docket No: P39855-WO-1(iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and(b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks at a dose of about 150 mg,wherein the anti-TL1 A antibody comprises the following CDRs:(a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3;(b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4;(c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5;(d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6;(e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and(f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

56. A method of treating CD in a pediatric patient having a body weight of at least 10 kg and less than 35 kg, the method comprising administering to the patient an effective amount of an anti-TL1 A antibody in a dosing regimen comprising an induction phase and a maintenance phase, wherein:(a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 8 mg / kg, wherein the dose does not exceed 250 mg, wherein:(i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose;(ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and(iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and(b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks at a dose of about 50 mg,wherein the anti-TL1 A antibody comprises the following CDRs:(a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3;(b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4;(c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5;(d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6;(e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and(f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

57. A method of treating CD in a pediatric patient having a body weight of at least 35 kg, the method comprising administering to the patient an effective amount of an anti-TL1 A antibody in a dosing regimen comprising an induction phase and a maintenance phase, wherein:(a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 500 mg, wherein:(i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose;PATENTAttorney Docket No: 50474-373WO3Genentech Docket No: P39855-WO-1(ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and(iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and(b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks at a dose of about 450 mg,wherein the anti-TL1 A antibody comprises the following CDRs:(a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3;(b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4;(c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5;(d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6;(e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and(f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

58. A method of treating CD in a pediatric patient having a body weight of at least 35 kg, the method comprising administering to the patient an effective amount of an anti-TL1 A antibody in a dosing regimen comprising an induction phase and a maintenance phase, wherein:(a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 250 mg, wherein:(i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose;(ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and(iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and(b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks at a dose of about 150 mg,wherein the anti-TL1 A antibody comprises the following CDRs:(a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3;(b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4;(c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5;(d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6;(e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and(f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

59. The method of any one of claims 1-32, 37-45, and 55-58, wherein, in a population of patients treated according to the method, the treating results in an increase in the proportion of patients who have achieved clinical remission at the end of the induction phase as compared to a reference population.PATENTAttorney Docket No: 50474-373WO3Genentech Docket No: P39855-WO-160. The method of claim 59, wherein the induction phase has a duration of about 12 weeks, and the treating results in an increase in the proportion of patients who have achieved clinical remission at Week 12.

61. The method of any one of claims 2-32, 37-45, and 55-58, wherein, in a population of patients treated according to the method, the treating results in an increase in the proportion of patients who have achieved clinical remission at the end of the maintenance phase as compared to a reference population.

62. The method of claim 61 , wherein the dosing regimen has a duration of about 52 weeks, and the treating results in an increase in the proportion of patients who have achieved clinical remission at Week 52.

63. The method of any one of claims 59-62, wherein clinical remission is a pediatric Crohn’s disease activity index (PCDAI) of less than 10.

64. The method of any one of claims 1-32, 37-45, and 55-63, wherein, in a population of patients treated according to the method, the treating results in an increase in the proportion of patients who have achieved an endoscopic response at the end of the induction phase as compared to a reference population.

65. The method of claim 64, wherein the induction phase has a duration of about 12 weeks, and the treating results in an increase in the proportion of patients who have achieved an endoscopic response at Week 12.

66. The method of any one of claims 1-32, 37-45, and 55-65, wherein, in a population of patients treated according to the method, the treating results in an increase in the proportion of patients who have achieved an endoscopic response at the end of the maintenance phase as compared to a reference population.

67. The method of claim 66, wherein the dosing regimen has a duration of about 52 weeks, and the treating results in an increase in the proportion of patients who have achieved an endoscopic response at Week 52.

68. The method of any one of claims 64-67, wherein an endoscopic response is a Simple Endoscopic Score for Crohn’s Disease (SES-CD) that is at least 50% lower than a baseline SES-CD.

69. The method of any one of claims 50-54 and 59-68, wherein the reference population is a population of patients who have not been treated with an anti-TL1 A antibody.PATENTAttorney Docket No: 50474-373WO3Genentech Docket No: P39855-WO-170. The method of any one of claims 1-69, wherein the patient has been determined to be a haplotype B non-carrier for TNFSF15.71 . The method of any one of claims 1-70, wherein the anti-TL1 A antibody comprises:(a) a heavy chain variable (VH) domain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 1 ; and / or(b) a light chain variable (VL) domain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 2.

72. The method of claim 71 , wherein the anti-TL1 A 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.

73. The method of claim 72, wherein the anti-TL1 A antibody comprises:(a) a VH domain comprising the amino acid sequence of SEQ ID NO: 1 ; and(b) a VL domain comprising the amino acid sequence of SEQ ID NO: 2.

74. The method of any one of claims 1-73, wherein the anti-TL1 A antibody comprises:(a) a heavy chain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 9 or SEQ ID NO: 11 ; and / or(b) a light chain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 10.

75. The method of claim 74, wherein the anti-TL1 A antibody comprises:(a) a heavy chain comprising the amino acid sequence of SEQ ID NO: 9; and / or(b) a light chain comprising the amino acid sequence of SEQ ID NO: 10.

76. The method of claim 75, wherein the anti-TL1 A antibody comprises:(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.

77. The method of any one of claims 1-76, wherein the anti-TL1 A antibody is afimkibart.

78. A method of treating an inflammatory bowel disease (IBD) in a pediatric patient, the method comprising administering to the patient an effective amount of an anti-TNF-like ligand 1 A (TL1 A) antibody in a dosing regimen comprising an induction phase, wherein the induction phase comprises administration of only four doses of the anti-TL1 A antibody, wherein:(i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose;PATENTAttorney Docket No: 50474-373WO3Genentech Docket No: P39855-WO-1(ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and(iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose;wherein the anti-TL1 A antibody comprises:(a) a heavy chain comprising an amino acid sequence having the amino acid sequence of SEQ ID NO: 9; and(b) a light chain comprising an amino acid sequence having the amino acid sequence of SEQ ID NO: 10.

79. The method of claim 78, wherein the IBD is UC.

80. The method of claim 78, wherein the IBD is CD.

81. A method of treating an IBD in a pediatric patient, the method comprising administering to the patient an effective amount of an anti-TL1 A antibody in a dosing regimen comprising an induction phase and a maintenance phase, wherein:(a) the induction phase comprises administration of only four doses of the anti-TL1 A antibody, wherein:(i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose;(ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and(iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and(b) the maintenance phase comprises administration of the anti-TL1 A antibody every four weeks; wherein the anti-TL1 A antibody comprises:(a) a heavy chain comprising an amino acid sequence having the amino acid sequence of SEQ ID NO: 9; and(b) a light chain comprising an amino acid sequence having the amino acid sequence of SEQ ID NO: 10.

82. The method of claim 81 , wherein the IBD is UC.

83. The method of claim 81 , wherein the IBD is CD.

84. A kit comprising an anti-TNF-like ligand 1 A (TL1 A) antibody and a package insert comprising instructions for using the antibody for treating an inflammatory bowel disease (IBD) in a pediatric patient in need thereof according to the method of any one of claims 1-83.PATENTAttorney Docket No: 50474-373WO3Genentech Docket No: P39855-WO-185. An anti-TL1 A antibody for use in treating an IBD in a pediatric patient, wherein an effective amount of an anti-TL1 A antibody is to be administered to the patient in a dosing regimen comprising an induction phase, wherein the induction phase comprises administration of only four doses of the anti-TL1 A antibody, wherein:(i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and(iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose, wherein the anti-TL1 A antibody comprises the following complementarity-determining regions (CDRs): (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3;(b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4;(c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5;(d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6;(e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and(f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

86. An anti-TL1 A antibody for use in treating an IBD in a pediatric patient, wherein an effective amount of an anti-TL1 A antibody is to be administered to the patient in a dosing regimen comprising an induction phase and a maintenance phase, wherein:(a) the induction phase comprises administration of only four doses of the anti-TL1 A antibody, wherein:(i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose;(ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and(iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and(b) the maintenance phase comprises administration of the anti-TL1 A antibody every four weeks, wherein the anti-TL1 A antibody comprises the following CDRs:(a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3;(b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4;(c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5;(d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6;(e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and(f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

87. An anti-TL1 A antibody for use in treating UC in a pediatric patient having a body weight of at least 10 kg and less than 35 kg, wherein an effective amount of the anti-TL1 A antibody is to be administered to the patient in a dosing regimen comprising an induction phase and a maintenance phase, wherein:PATENTAttorney Docket No: 50474-373WO3Genentech Docket No: P39855-WO-1(a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 16 mg / kg, wherein the dose does not exceed 500 mg, wherein:(i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose;(ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and(iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and(b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks at a dose of about 150 mg,wherein the anti-TL1 A antibody comprises the following CDRs:(a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3;(b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4;(c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5;(d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6;(e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and(f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

88. An anti-TL1 A antibody for use in treating UC in a pediatric patient having a body weight of at least 10 kg and less than 35 kg, wherein an effective amount of the anti-TL1 A antibody is to be administered to the patient in a dosing regimen comprising an induction phase and a maintenance phase, wherein:(a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 8 mg / kg, wherein the dose does not exceed 250 mg, wherein:(i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose;(ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and(iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and(b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks at a dose of about 50 mg,wherein the anti-TL1 A antibody comprises the following CDRs:(a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3;(b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4;(c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5;(d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6;(e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and(f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.PATENTAttorney Docket No: 50474-373WO3Genentech Docket No: P39855-WO-189. An anti-TL1 A antibody for use in treating UC in a pediatric patient having a body weight of at least 35 kg, wherein an effective amount of an anti-TL1 A antibody is to be administered to the patient in a dosing regimen comprising an induction phase and a maintenance phase, wherein:(a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 500 mg, wherein:(i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose;(ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and(iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and(b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks at a dose of about 450 mg,wherein the anti-TL1 A antibody comprises the following CDRs:(a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3;(b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4;(c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5;(d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6;(e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and(f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

90. An anti-TL1 A antibody for use in treating UC in a pediatric patient having a body weight of at least 35 kg, wherein an effective amount of an anti-TL1 A antibody is to be administered to the patient in a dosing regimen comprising an induction phase and a maintenance phase, wherein:(a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 250 mg, wherein:(i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose;(ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and(iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and(b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks at a dose of about 150 mg,wherein the anti-TL1 A antibody comprises the following CDRs:(a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3;(b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4;(c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5;(d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6;(e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; andPATENTAttorney Docket No: 50474-373WO3Genentech Docket No: P39855-WO-1(f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.91 . An anti-TL1 A antibody for use in treating CD in a pediatric patient having a body weight of at least 10 kg and less than 35 kg, wherein an effective amount of the anti-TL1 A antibody is to be administered to the patient in a dosing regimen comprising an induction phase and a maintenance phase, wherein:(a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 16 mg / kg, wherein the dose does not exceed 500 mg, wherein:(i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose;(ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and(iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and(b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks at a dose of about 150 mg,wherein the anti-TL1 A antibody comprises the following CDRs:(a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3;(b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4;(c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5;(d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6;(e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and(f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

92. An anti-TL1 A antibody for use in treating CD in a pediatric patient having a body weight of at least 10 kg and less than 35 kg, wherein an effective amount of the anti-TL1 A antibody is to be administered to the patient in a dosing regimen comprising an induction phase and a maintenance phase, wherein:(a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 8 mg / kg, wherein the dose does not exceed 250 mg, wherein:(i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose;(ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and(iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and(b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks at a dose of about 50 mg,wherein the anti-TL1 A antibody comprises the following CDRs:(a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3;(b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4;(c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5;PATENTAttorney Docket No: 50474-373WO3Genentech Docket No: P39855-WO-1(d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6;(e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and(f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

93. An anti-TL1 A antibody for use in treating CD in a pediatric patient having a body weight of at least 35 kg, wherein an effective amount of an anti-TL1 A antibody is to be administered to the patient in a dosing regimen comprising an induction phase and a maintenance phase, wherein:(a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 500 mg, wherein:(i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose;(ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and(iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and(b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks at a dose of about 450 mg,wherein the anti-TL1 A antibody comprises the following CDRs:(a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3;(b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4;(c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5;(d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6;(e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and(f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

94. An anti-TL1 A antibody for use in treating CD in a pediatric patient having a body weight of at least 35 kg, wherein an effective amount of an anti-TL1 A antibody is to be administered to the patient in a dosing regimen comprising an induction phase and a maintenance phase, wherein:(a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 250 mg, wherein:(i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose;(ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and(iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and(b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks at a dose of about 150 mg,wherein the anti-TL1 A antibody comprises the following CDRs:(a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3;PATENTAttorney Docket No: 50474-373WO3Genentech Docket No: P39855-WO-1(b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4;(c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5;(d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6;(e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and(f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

95. An anti-TL1 A antibody for use in treating an IBD in a pediatric patient, wherein an effective amount of an anti-TL1 A antibody is to be administered to the patient in a dosing regimen comprising an induction phase, wherein the induction phase comprises administration of only four doses of the anti-TL1 A antibody, wherein:(i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose;(ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and(iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose;wherein the anti-TL1 A antibody comprises:(a) a heavy chain comprising an amino acid sequence having the amino acid sequence of SEQ ID NO: 9; and(b) a light chain comprising an amino acid sequence having the amino acid sequence of SEQ ID NO: 10.

96. An anti-TL1 A antibody for use in treating an IBD in a pediatric patient, wherein an effective amount of an anti-TL1 A antibody is to be administered to the patient in a dosing regimen comprising an induction phase and a maintenance phase, wherein:(a) the induction phase comprises administration of only four doses of the anti-TL1 A antibody, wherein:(i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose;(ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and(iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and(b) the maintenance phase comprises administration of the anti-TL1 A antibody every four weeks; wherein the anti-TL1 A antibody comprises:(a) a heavy chain comprising an amino acid sequence having the amino acid sequence of SEQ ID NO: 9; and(b) a light chain comprising an amino acid sequence having the amino acid sequence of SEQ ID NO: 10.PATENTAttorney Docket No: 50474-373WO3Genentech Docket No: P39855-WO-197. Use of an anti-TL1 A antibody in the manufacture of a medicament for treating an IBD in a pediatric patient, wherein an effective amount of an anti-TL1 A antibody is to be administered to the patient in a dosing regimen comprising an induction phase, wherein the induction phase comprises administration of only four doses of the anti-TL1 A antibody, wherein:(i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose; (ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and(iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose, wherein the anti-TL1 A antibody comprises the following complementarity-determining regions (CDRs):(a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3;(b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4;(c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5;(d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6;(e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and(f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

98. Use of an anti-TL1 A antibody in the manufacture of a medicament for treating an IBD in a pediatric patient, wherein an effective amount of an anti-TL1 A antibody is to be administered to the patient in a dosing regimen comprising an induction phase and a maintenance phase, wherein:(a) the induction phase comprises administration of only four doses of the anti-TL1 A antibody, wherein:(i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose;(ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and(iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and(b) the maintenance phase comprises administration of the anti-TL1 A antibody every four weeks, wherein the anti-TL1 A antibody comprises the following CDRs:(a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3;(b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4;(c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5;(d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6;(e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and(f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

99. Use of an anti-TL1 A antibody in the manufacture of a medicament for treating UC in a pediatric patient having a body weight of at least 10 kg and less than 35 kg, wherein an effective amount of thePATENTAttorney Docket No: 50474-373WO3Genentech Docket No: P39855-WO-1anti-TL1 A antibody is to be administered to the patient in a dosing regimen comprising an induction phase and a maintenance phase, wherein:(a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 16 mg / kg, wherein the dose does not exceed 500 mg, wherein:(i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose;(ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and(iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and(b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks at a dose of about 150 mg,wherein the anti-TL1 A antibody comprises the following CDRs:(a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3;(b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4;(c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5;(d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6;(e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and(f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

100. Use of an anti-TL1 A antibody in the manufacture of a medicament for treating UC in a pediatric patient having a body weight of at least 10 kg and less than 35 kg, wherein an effective amount of the anti-TL1 A antibody is to be administered to the patient in a dosing regimen comprising an induction phase and a maintenance phase, wherein:(a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 8 mg / kg, wherein the dose does not exceed 250 mg, wherein:(i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose;(ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and(iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and(b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks at a dose of about 50 mg,wherein the anti-TL1 A antibody comprises the following CDRs:(a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3;(b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4;(c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5;(d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6;(e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; andPATENTAttorney Docket No: 50474-373WO3Genentech Docket No: P39855-WO-1(f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

101. Use of an anti-TL1 A antibody in the manufacture of a medicament for treating UC in a pediatric patient having a body weight of at least 35 kg, wherein an effective amount of an anti-TL1A antibody is to be administered to the patient in a dosing regimen comprising an induction phase and a maintenance phase, wherein:(a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 500 mg, wherein:(i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose;(ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and(iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and(b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks at a dose of about 450 mg,wherein the anti-TL1 A antibody comprises the following CDRs:(a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3;(b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4;(c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5;(d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6;(e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and(f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

102. Use of an anti-TL1 A antibody in the manufacture of a medicament for treating UC in a pediatric patient having a body weight of at least 35 kg, wherein an effective amount of an anti-TL1A antibody is to be administered to the patient in a dosing regimen comprising an induction phase and a maintenance phase, wherein:(a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 250 mg, wherein:(i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose;(ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and(iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and(b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks at a dose of about 150 mg,wherein the anti-TL1 A antibody comprises the following CDRs:(a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3;PATENTAttorney Docket No: 50474-373WO3Genentech Docket No: P39855-WO-1(b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4;(c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5;(d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6;(e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and(f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

103. Use of an anti-TL1 A antibody in the manufacture of a medicament for treating CD in a pediatric patient having a body weight of at least 10 kg and less than 35 kg, wherein an effective amount of the anti-TL1 A antibody is to be administered to the patient in a dosing regimen comprising an induction phase and a maintenance phase, wherein:(a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 16 mg / kg, wherein the dose does not exceed 500 mg, wherein:(i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose;(ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and(iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and(b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks at a dose of about 150 mg,wherein the anti-TL1 A antibody comprises the following CDRs:(a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3;(b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4;(c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5;(d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6;(e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and(f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

104. Use of an anti-TL1 A antibody in the manufacture of a medicament for treating CD in a pediatric patient in a pediatric patient having a body weight of at least 10 kg and less than 35 kg, wherein an effective amount of the anti-TL1 A antibody is to be administered to the patient in a dosing regimen comprising an induction phase and a maintenance phase, wherein:(a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 8 mg / kg, wherein the dose does not exceed 250 mg, wherein:(i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose;(ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and(iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; andPATENTAttorney Docket No: 50474-373WO3Genentech Docket No: P39855-WO-1(b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks at a dose of about 50 mg,wherein the anti-TL1 A antibody comprises the following CDRs:(a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3;(b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4;(c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5;(d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6;(e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and(f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

105. Use of an anti-TL1 A antibody in the manufacture of a medicament for treating CD in a pediatric patient having a body weight of at least 35 kg, wherein an effective amount of an anti-TL1A antibody is to be administered to the patient in a dosing regimen comprising an induction phase and a maintenance phase, wherein:(a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 500 mg, wherein:(i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose;(ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and(iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and(b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks at a dose of about 450 mg,wherein the anti-TL1 A antibody comprises the following CDRs:(a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3;(b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4;(c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5;(d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6;(e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and(f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

106. Use of an anti-TL1 A antibody in the manufacture of a medicament for treating CD in a pediatric patient having a body weight of at least 35 kg, wherein an effective amount of an anti-TL1A antibody is to be administered to the patient in a dosing regimen comprising an induction phase and a maintenance phase, wherein:(a) the induction phase comprises intravenous administration of only four doses of the anti-TL1 A antibody at a dose of about 250 mg, wherein:(i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose;PATENTAttorney Docket No: 50474-373WO3Genentech Docket No: P39855-WO-1(ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and(iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and(b) the maintenance phase comprises subcutaneous administration of the anti-TL1 A antibody every four weeks at a dose of about 150 mg,wherein the anti-TL1 A antibody comprises the following CDRs:(a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3;(b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 4;(c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 5;(d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 6;(e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 7; and(f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 8.

107. Use of an anti-TL1 A antibody in the manufacture of a medicament for treating an IBD in a pediatric patient, wherein an effective amount of an anti-TL1 A antibody is to be administered to the patient in a dosing regimen comprising an induction phase, wherein the induction phase comprises administration of only four doses of the anti-TL1 A antibody, wherein:(i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose;(ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; and(iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose;wherein the anti-TL1 A antibody comprises:(a) a heavy chain comprising an amino acid sequence having the amino acid sequence of SEQ ID NO: 9; and(b) a light chain comprising an amino acid sequence having the amino acid sequence of SEQ ID NO: 10.

108. Use of an anti-TL1 A antibody in the manufacture of a medicament for treating an IBD in a pediatric patient, wherein an effective amount of an anti-TL1 A antibody is to be administered to the patient in a dosing regimen comprising an induction phase and a maintenance phase, wherein:(a) the induction phase comprises administration of only four doses of the anti-TL1 A antibody, wherein:(i) the second dose of the anti-TL1 A antibody is administered about two weeks after the first dose;(ii) the third dose of the anti-TL1 A antibody is administered about four weeks after the second dose; andPATENTAttorney Docket No: 50474-373WO3Genentech Docket No: P39855-WO-1(iii) the fourth dose of the anti-TL1 A antibody is administered about four weeks after the third dose; and(b) the maintenance phase comprises administration of the anti-TL1 A antibody every four weeks; wherein the anti-TL1 A antibody comprises:(a) a heavy chain comprising an amino acid sequence having the amino acid sequence of SEQ ID NO: 9; and(b) a light chain comprising an amino acid sequence having the amino acid sequence of SEQ ID NO: 10.

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