📚 Part of the TILA-278 Regulatory Dossier — Reader's Guide. This article shows the live document; edits to the source appear here automatically.

---

Clinical Development Plan (TILA-278)

Field	Value
Document ID	PM-007
Version	1.0
Compound	TILA-278 (anti-TL1A antagonist / IL-22R agonist bispecific)
Standard	program management
Confidentiality	Confidential

Program-management document for the TILA-278 development program.

Change History

Version	Date	Author	Summary
1.0	2026-07-08	Program Management	Initial issue

Program-level development plan for TILA-278 in ulcerative colitis, integrating the completed Phase 2b induction study (TILA278-201) with the proposed confirmatory Phase 3 program and the supporting nonclinical, clinical-pharmacology, and CMC activities. Pivotal figures trace to Study TILA278-201.

1. Purpose and Scope

This Clinical Development Plan (CDP) defines the strategy, design rationale, and decision framework for the clinical development of TILA-278 (Virtual Biopharma Inc.) for the treatment of moderate-to-severe ulcerative colitis (UC). It integrates the results of the completed Phase 2b dose-finding induction study (Protocol TILA278-201) with the proposed Phase 3 confirmatory program and the associated regulatory, nonclinical, clinical pharmacology, and Chemistry, Manufacturing, and Controls (CMC) supporting activities.

The plan serves as the program-management reference document for the transition from Phase 2b to Phase 3, anchors the End-of-Phase-2 (EOP2) interaction with the U.S. Food and Drug Administration (FDA) and the corresponding Scientific Advice procedure with the European Medicines Agency (EMA), and establishes the pre-specified go/no-go criteria governing subsequent investment decisions. It is written to be consistent with ICH E8(R1) (General Considerations for Clinical Studies), ICH E9(R1) (estimands and sensitivity analysis), and ICH E6(R3) (Good Clinical Practice).

2. Product and Program Overview

TILA-278 is a recombinant humanized immunoglobulin G1 (IgG1) bispecific monoclonal antibody administered subcutaneously (SC). The molecule engages two complementary, non-redundant pathways implicated in the pathophysiology of UC:

• Anti-TL1A (TNFSF15) antagonist arm — neutralizes TL1A signaling through death receptor 3 (DR3), dampening TH1/TH17-driven mucosal inflammation and attenuating the pro-fibrotic signaling associated with intestinal fibrosis and a stricturing disease course.
• IL-22 receptor (IL-22R) agonist arm — engages the IL-22RA1/IL-10RB receptor complex on intestinal epithelial cells to drive epithelial regeneration, mucin and antimicrobial-peptide production, and mucosal-barrier repair.

The dual mechanism couples an anti-inflammatory effect (TL1A antagonism) with an active mucosal-healing effect (IL-22R agonism) within a single molecular entity, addressing both the inflammatory and the barrier-dysfunction components of UC that mono-mechanistic biologics do not simultaneously target. The therapeutic hypothesis is that this combination will deliver deeper and more durable remission — including endoscopic and histologic healing — than is achievable with anti-inflammatory blockade alone.

3. Target Product Profile

The Target Product Profile (TPP) frames the development objectives and provides the reference standard against which go/no-go decisions and label projections are assessed.

Attribute	Minimum acceptable	Aspirational (base case)
Indication	Induction and maintenance of clinical remission in adults with moderate-to-severe UC with inadequate response, loss of response, or intolerance to conventional therapy	Same, positioned for use across biologic-naïve and biologic-experienced populations
Population	Second-line and later (post-biologic)	First-line advanced therapy and post-biologic
Mechanism	Anti-TL1A antagonism	Dual anti-TL1A antagonism + IL-22R agonism (inflammation control plus mucosal healing)
Route / presentation	SC injection, healthcare-administered	SC self-administration via single-use prefilled syringe and autoinjector
Induction efficacy	Clinical remission superior to placebo at Week 12	Clinical remission ≥30% with dose-ordered endoscopic and histologic healing
Maintenance efficacy	Superiority to placebo for clinical remission at Week 52 in induction responders	Corticosteroid-free remission and durable endoscopic-histologic healing at Week 52
Dosing frequency	Induction more frequent than maintenance	Induction every 2 weeks (Q2W) SC; maintenance every 4 weeks (Q4W) SC
Safety / tolerability	Safety profile consistent with class; no dose-dependent safety signal	No new safety signals; principal drug-attributable finding limited to injection-site reactions
Immunogenicity	Anti-drug antibodies (ADA) without clinically meaningful impact on efficacy/safety	Low ADA incidence with no meaningful impact on exposure or response

4. Development Strategy Overview

The clinical program follows a conventional, regulatory-endorsed UC development paradigm structured to move efficiently from proof-of-concept to registration:

1. Phase 1 (first-in-human): single- and multiple-ascending-dose SC study characterizing safety, tolerability, pharmacokinetics (PK), and immunogenicity, and bridging the drug-product presentations.
2. Phase 2b (dose-finding induction): completed Study TILA278-201, establishing efficacy, dose-response, and the induction dose for Phase 3 (Section 5).
3. Phase 3 (confirmatory): a replicate-induction plus maintenance program supporting registration of both an induction and a maintenance claim (Section 6).
4. Lifecycle: long-term extension for durability and safety, pediatric development, and planned label expansion into related indications (Section 10.4).

The strategy is designed so that a single dose selected on the totality of the Phase 2b data carries into confirmatory testing, minimizing exposure of the confirmatory program to dose-selection risk while preserving the option to characterize an alternative maintenance interval.

5. Completed and Ongoing Studies

5.1 Phase 2b Study TILA278-201 — design

TILA278-201 was a multicenter, randomized, double-blind, placebo-controlled, parallel-group, 12-week induction study in adults (18–75 years) with moderate-to-severe active UC (baseline modified Mayo score 4–9, centrally read endoscopy subscore ≥2, rectal bleeding subscore ≥1). Of 1,700 subjects screened, 900 were randomized 1:1:1 to TILA-278 High (n=299), TILA-278 Low (n=300), or placebo (n=301). Randomization was performed centrally via interactive response technology and stratified by baseline modified Mayo severity (4–6 vs 7–9) and prior biologic exposure (yes vs no). Study drug was administered SC at Weeks 0, 2, 4, and 8, with the Week 12 visit serving as the End-of-Treatment assessment; protocol assessments occurred at Weeks 0, 2, 4, 8, and 12. An independent Data Safety Monitoring Board provided ongoing safety oversight throughout the study.

A total of 840 subjects received at least one dose and had a baseline and at least one post-baseline efficacy assessment, comprising both the Full Analysis Set (FAS) and the Safety Set: TILA-278 High 284, TILA-278 Low 283, placebo 273. Sixty randomized subjects (High 15, Low 17, placebo 28) were not dosed or lacked a post-baseline assessment and were excluded from the analysis populations.

The primary endpoint was clinical remission at Week 12, defined as a modified Mayo score ≤2 with no individual subscore >1. Key secondary endpoints were change from baseline in modified Mayo score and endoscopic improvement at Week 12.

5.2 Phase 2b efficacy results

Both active doses met the primary endpoint with a clear, dose-ordered response and were statistically superior to placebo. The primary binary endpoint was analyzed by a stratified Cochran-Mantel-Haenszel (CMH) test with non-responder imputation; the continuous key secondary endpoint was analyzed by ANCOVA. The two analyses were concordant.

Table 5.2-1. Week-12 efficacy (FAS)

Analysis	TILA-278 High (N=284)	TILA-278 Low (N=283)	Placebo (N=273)
Primary — clinical remission (modified Mayo ≤2, no subscore >1; CMH, NRI)
Clinical remission, n/N (%)	106/284 (37.3%)	46/283 (16.2%)	2/273 (0.7%)
Risk difference vs placebo, pp (95% CI)	+36.6 (30.9, 42.3)	+15.5 (11.1, 19.9)	—
p-value vs placebo	<0.0001	<0.0001	—
Key secondary — change in modified Mayo (ANCOVA)
LS-mean change from baseline	−3.36	−2.76	−1.00
LS-mean difference vs placebo (95% CI)	−2.36 (−2.49, −2.23)	−1.77 (−1.90, −1.64)	—
p-value vs placebo	<0.0001	<0.0001	—

The High dose achieved clinical remission in 37.3% of subjects versus 0.7% on placebo — a risk difference of +36.6 percentage points (95% CI 30.9 to 42.3; p<0.0001) — with the Low dose intermediate at 16.2% (+15.5 percentage points; 95% CI 11.1 to 19.9; p<0.0001). The near-nil placebo remission rate, the consistent dose-ordering (High > Low > placebo) across both the responder-based and the continuous analyses, and concordant reductions in C-reactive protein and faecal calprotectin together provide a robust basis for dose selection.

5.3 Phase 2b safety results

Table 5.3-1. Overview of treatment-emergent adverse events (Safety Set; subjects, n [%])

Parameter	TILA-278 High (N=284)	TILA-278 Low (N=283)	Placebo (N=273)
≥1 TEAE	109 (38.4%)	131 (46.3%)	130 (47.6%)
Serious adverse events	3 (1.1%)	0	4 (1.5%)
Deaths (all assessed as unrelated)	2 (0.7%)	0	1 (0.4%)
Discontinued study	17 (6.0%)	17 (6.0%)	29 (10.6%)

The most frequently reported adverse events were nasopharyngitis, headache, worsening UC (more frequent on placebo), anaemia, arthralgia, upper respiratory tract infection, injection-site reactions (more frequent on active SC drug), and nausea. The proportion of subjects with at least one TEAE was similar across arms and did not increase with dose. Discontinuations and worsening UC were most frequent on placebo and were driven by lack of efficacy. The small number of deaths (High 2, Low 0, placebo 1) were all investigator-assessed as unrelated to study drug, and serious adverse events were numerically lower on both active doses than on placebo. No dose-dependent safety signal was identified; injection-site reactions were the principal drug-attributable finding, consistent with the SC route and the antibody class.

5.4 Dose selection for Phase 3

On the totality of the data — a substantially higher clinical remission rate, the largest LS-mean reduction in modified Mayo score, dose-ordered efficacy, concordant endoscopic and biomarker findings, and the absence of a dose-dependent safety signal — the TILA-278 High dose is selected as the Phase 3 induction dose. The maintenance regimen will evaluate a less-frequent SC interval consistent with the molecule's PK (Section 6.4). Exposure-response modeling anchored to TILA278-201 supports that the High dose lies on the plateau of the efficacy-exposure relationship while remaining well tolerated.

6. Phase 3 Program Design

The Phase 3 program comprises two replicate induction studies, one maintenance study using a randomized-withdrawal (responder re-randomization) design, and a long-term extension. This structure supports separate induction and maintenance claims within a single integrated label, consistent with regulatory expectations for advanced therapies in UC. An independent Data Monitoring Committee provides ongoing safety oversight across the program, consistent with the oversight model used in TILA278-201.

Study	Design	Phase / duration	Population	Planned N	Primary objective
TILA278-301	Randomized (2:1, TILA-278: placebo), double-blind, placebo-controlled	Induction, 12 weeks	Moderate-to-severe UC; conventional- and biologic-experienced strata	~700	Clinical remission at Week 12
TILA278-302	Randomized (2:1), double-blind, placebo-controlled (replicate)	Induction, 12 weeks	As TILA278-301	~700	Clinical remission at Week 12
TILA278-303	Randomized-withdrawal, double-blind, placebo-controlled	Maintenance, through Week 52	Week-12 clinical responders from 301/302	~600 re-randomized	Clinical remission at Week 52
TILA278-304	Open-label long-term extension	Up to Week 152	Completers of 303	All eligible	Long-term safety and durability

6.1 Induction studies (TILA278-301, TILA278-302)

Two identically designed, geographically distributed induction studies randomize subjects 2:1 to TILA-278 High (induction regimen) or placebo. Randomization is stratified by baseline modified Mayo severity, prior biologic/advanced-therapy exposure, and concomitant corticosteroid use. The 12-week induction period mirrors TILA278-201 to preserve comparability of the efficacy estimate. Replicate studies provide the two adequate and well-controlled trials expected to establish substantial evidence of effectiveness. Sample sizes are anchored to the Phase 2b treatment effect using deliberately conservative placebo-remission and treatment-difference assumptions, and are powered to support the ranked key secondary endpoints (endoscopic and endoscopic-histologic healing) in addition to the primary endpoint.

6.2 Maintenance study (TILA278-303)

Subjects achieving clinical response at Week 12 in either induction study are re-randomized in a double-blind fashion to continued TILA-278 (maintenance regimen) or withdrawal to placebo, and followed through Week 52. This randomized-withdrawal design isolates the maintenance effect of continued therapy and supports a corticosteroid-free remission claim. Induction non-responders and re-randomized subjects who lose response follow pre-specified rescue/escape pathways with appropriate analysis handling under the estimand framework (Section 7).

6.3 Long-term extension (TILA278-304)

An open-label extension enrolls maintenance-study completers to characterize durability of remission, endoscopic and histologic healing over time, long-term safety, and immunogenicity, and to support the periodic benefit-risk evaluation and post-marketing commitments.

6.4 Dose and regimen rationale

Phase 3 uses the Phase 2b High dose for induction (Q2W SC) and evaluates a Q4W SC maintenance interval, supported by population-PK and exposure-response modeling anchored to TILA278-201 observed exposures. PK is expected to be governed by target-mediated drug disposition (TMDD) with characteristic non-linearity at lower concentrations; SC bioavailability, TMDD, and the impact of ADA on exposure are prospectively incorporated into the model to justify the maintenance interval. No dedicated thorough-QT study is planned; the ICH E14/S7B waiver rationale for a monoclonal antibody with no expectation of direct ion-channel interaction applies.

7. Key Endpoints and Estimands

Phase 3 endpoints are defined to satisfy contemporary FDA and EMA expectations for UC, which require objective (endoscopic) and, increasingly, histologic evidence of healing in addition to symptomatic control. The Phase 3 remission definition adopts the regulator-preferred component-based modified Mayo definition, harmonized with the definition used in TILA278-201 (modified Mayo ≤2 with no individual subscore >1); the precise operational definition is a designated topic for EOP2 alignment (Sections 8 and 10.3).

Tier	Induction (Week 12)	Maintenance (Week 52)
Primary	Clinical remission — rectal bleeding subscore 0, stool-frequency subscore ≤1 and not increased from baseline, endoscopy subscore ≤1	Clinical remission at Week 52 among Week-12 responders
Key secondary	Endoscopic improvement; clinical response; symptomatic remission; bowel-urgency improvement	Corticosteroid-free clinical remission; durable remission (remission at both Week 12 and Week 52); endoscopic improvement
Additional	Endoscopic-histologic mucosal improvement (HEMI); IBDQ quality of life; biomarkers (faecal calprotectin, CRP)	HEMI; maintenance of endoscopic-histologic healing; sustained corticosteroid-free remission

Estimands are defined per ICH E9(R1). For the binary primary endpoint the primary estimand adopts a composite strategy: pre-specified intercurrent events — discontinuation of study treatment for lack of efficacy, initiation of prohibited rescue medication or advanced therapy, and UC-related surgery — are incorporated into the endpoint as treatment failure (non-responder imputation), and subjects with missing Week-12 status are likewise classified as non-responders. Tipping-point and multiple-imputation analyses assess robustness. For continuous endpoints, a treatment-policy strategy estimated by a mixed-model repeated-measures (MMRM) approach serves as the principal sensitivity framework. Strong control of the family-wise type I error rate at two-sided 0.05 is maintained across the primary and ranked key secondary endpoints via a pre-specified graphical (hierarchical) multiplicity procedure spanning both induction studies and the maintenance study.

8. Go/No-Go Decision Criteria

Decision gates are pre-specified to govern progression and investment. The Phase 2b gate has been met; subsequent gates are defined for the confirmatory program.

Gate	Timing	Go criterion	No-go / hold criterion
G1 — Phase 2b → Phase 3	Completed (TILA278-201)	Met: statistically significant, dose-ordered clinical remission at Week 12 (High 37.3% vs placebo 0.7%; +36.6 pp; p<0.0001) with no dose-dependent safety signal	Failure to separate from placebo, or a dose-limiting safety signal
G2 — EOP2 alignment	Q4 2026	FDA and EMA concurrence on Phase 3 design, endpoints, dose, and remission definition	Unresolved design/endpoint disagreement requiring redesign
G3 — Induction readout	301/302 topline	Both induction studies meet the primary endpoint (statistically significant clinical remission at Week 12); benefit-risk consistent with Phase 2b	One or both induction studies fail primary; new clinically important safety signal
G4 — Maintenance readout	303 topline	Statistically significant Week-52 clinical remission in responders; corticosteroid-free remission supportive; acceptable long-term safety/immunogenicity	Maintenance primary not met; durability or safety concern precluding a viable label
G5 — Filing readiness	Pre-BLA/MAA	Integrated efficacy/safety databases, CMC process validation, and clin-pharm package complete and internally consistent	Material CMC comparability or safety-database gap

9. Supporting Development (Cross-References)

Registration-enabling activities across modules are aligned to the clinical timeline and are documented in their respective CTD sections; the CDP tracks their readiness against the filing date.

• CMC (Module 3): The drug substance is a recombinant humanized IgG1 bispecific monoclonal antibody expressed in a Chinese hamster ovary (CHO) cell line and purified by Protein-A capture, polishing chromatography, and dedicated viral-clearance steps. It is characterized for identity, higher-order structure, purity and product-/process-related impurities (aggregates/high-molecular-weight species, charge variants, fragments, and glycosylation), and for both functional activities — anti-TL1A neutralization and IL-22R agonism — by orthogonal potency assays, with Fc-mediated effector function characterized as part of the functional profile. A quality target product profile (QTPP) and the associated critical quality attributes and control strategy are established consistent with ICH Q5A–Q5E, Q6B, and Q8–Q11. The drug product is a sterile SC solution (formulation buffer with polysorbate) presented as a single-use prefilled syringe and autoinjector. Process performance qualification and comparability across the clinical and intended commercial presentations and scales are on the critical path to filing.
• Nonclinical (Module 4): Because TILA-278 is specific for human TL1A and human IL-22R, conventional rodents are not pharmacologically relevant; disease-model pharmacology is therefore conducted using a surrogate/knock-in approach, and repeat-dose SC toxicology is conducted in the cynomolgus monkey — confirmed as a pharmacologically relevant species on the basis of target cross-reactivity — supported by tissue cross-reactivity and safety-pharmacology assessments. Consistent with ICH S6(R1), standalone genotoxicity and 2-year rodent carcinogenicity studies are not warranted for a monoclonal antibody; given the proliferative pharmacology of IL-22R agonism, carcinogenic potential is addressed through a weight-of-evidence assessment and evaluation of proliferative and pre-neoplastic endpoints in the chronic cynomolgus study.
• Clinical pharmacology (Module 5; 2.7.1/2.7.2): PK is dominated by TMDD, with expected non-linearity at lower concentrations; SC bioavailability and the dose/exposure-response relationship anchored to TILA278-201 exposures inform the Phase 3 induction and maintenance regimens through population-PK modeling. Immunogenicity is assessed by a validated tiered assay (screening, confirmatory, titer, and neutralizing-antibody tiers) with pre-specified evaluation of ADA impact on PK, efficacy, and safety. No dedicated QT study is required; the ICH E14/S7B waiver rationale for a monoclonal antibody with no expectation of direct ion-channel (hERG) interaction applies.

10. Regulatory Strategy

10.1 Filing strategy (BLA / MAA)

Marketing applications will seek approval for both induction and maintenance of clinical remission in adults with moderate-to-severe UC.

• United States: Biologics License Application (BLA) under section 351(a) of the Public Health Service Act, filed in eCTD format. The two replicate induction studies plus the maintenance study are intended to constitute the substantial evidence of effectiveness.
• European Union: Marketing Authorisation Application (MAA) via the centralized procedure (mandatory for this monoclonal-antibody biologic), with the EMA as reference.
• Other regions: sequential filings in the United Kingdom (MHRA), Canada, Japan, and additional markets are planned following the primary-region submissions, leveraging the common technical dossier.

10.2 Expedited programs

Program	Region	Position
Fast Track	US (FDA)	Primary expedited vehicle; the serious, chronic nature of moderate-to-severe UC and the unmet need in advanced-therapy-experienced patients support a Fast Track request, enabling rolling BLA review
Breakthrough Therapy	US (FDA)	Pursued conditionally if Phase 3 (or a well-controlled comparative analysis) demonstrates substantial improvement over available therapy on a clinically significant endpoint, particularly in the biologic-experienced subgroup
PRIME	EU (EMA)	Considered on the strength of the dual-mechanism rationale and Phase 2b remission data; provides enhanced scientific and regulatory support
Accelerated / priority review	US / EU	Requested at filing based on the totality of benefit-risk

Designations contingent on comparative or subgroup evidence are flagged as decision-dependent and are not assumed in the base-case timeline.

10.3 Health-authority interactions

An EOP2 meeting with the FDA and a parallel EMA Scientific Advice procedure (with the option of an FDA/EMA parallel scientific-advice track) will be sought to align on the Phase 3 design, the primary and key-secondary endpoints and their multiplicity control, the remission definition, dose selection, the immunogenicity strategy, and the pediatric plan. Pre-BLA and pre-MAA meetings will confirm filing content and format.

10.4 Pediatric and lifecycle strategy

An initial Pediatric Study Plan (iPSP) will be submitted to the FDA and a Paediatric Investigation Plan (PIP) to the EMA, proposing deferral of pediatric studies until adult efficacy and safety are established, with a pediatric UC development program to follow. Lifecycle plans include the long-term extension (TILA278-304), evaluation of an alternative maintenance interval, self-administration/autoinjector human-factors support, and assessment of label expansion into adjacent indications (e.g., Crohn's disease) leveraging the dual anti-inflammatory/mucosal-healing mechanism.

10.5 Safety, pharmacovigilance, and risk management

A proactive pharmacovigilance and risk-management strategy is maintained across development and into the post-approval period, documented in the EU Risk Management Plan (GVP Module V), the US risk-management/REMS assessment, and periodic safety reporting (DSUR during development; PBRER/PSUR post-approval), consistent with ICH E2E. Based on the mechanism and the Phase 2b profile, the safety specification tracks: injection-site reactions and hypersensitivity; serious and opportunistic infections associated with immunomodulation (including tuberculosis reactivation), managed by protocol screening and monitoring; immunogenicity and its potential impact on exposure, efficacy, and safety; and, as an important potential risk warranting long-term surveillance, gastrointestinal epithelial proliferation and neoplasia, given the proliferative pharmacology of IL-22R agonism. The long-term extension (TILA278-304) together with routine and additional pharmacovigilance activities is structured to characterize these topics over extended exposure.

11. Timeline and Milestones

The base-case timeline assumes successful gate transitions (Section 8) and no design-altering health-authority feedback. Dates are planning targets.

Milestone	Target
Phase 2b TILA278-201 database lock and topline	Completed
EOP2 meeting (FDA) / Scientific Advice (EMA)	Q4 2026
Phase 3 induction studies (301/302) first-patient-in	Q1 2027
Maintenance study (303) initiation (rolling from induction responders)	Q3 2027
Induction topline (301/302)	H2 2028
Maintenance topline (303, Week 52)	H2 2029
BLA submission (rolling, under Fast Track)	H1 2030
MAA submission	H1 2030
Anticipated FDA action / EU opinion	2031

12. Risk Assessment and Mitigation

Risk	Impact	Mitigation
Higher placebo response in Phase 3 than in TILA278-201	Reduced treatment effect / underpowering	Central endoscopy reading, rigorous eligibility (objective inflammation required), enrichment via stratification, adequate sizing with a conservative delta
Failure to replicate across two induction studies	Filing risk at G3	Identical designs and endpoints, harmonized central reading, pre-specified pooled analyses
Immunogenicity affecting exposure/efficacy	Efficacy attenuation, safety	Tiered ADA assay with pre-specified PK/efficacy/safety impact analyses; regimen chosen to maintain exposure above the target-saturation threshold
Injection-site reactions affecting adherence in SC self-administration	Tolerability / adherence	Human-factors and device optimization; injection-technique guidance; monitoring in the long-term extension
CMC comparability across presentations and to commercial scale	Filing delay at G5	Early comparability protocol, process performance qualification aligned to the filing date, orthogonal potency assays for both binding activities
Expedited-designation dependence on comparative data	Timeline optimism	Base case relies only on Fast Track; Breakthrough/PRIME treated as upside, not assumed

The completed Phase 2b results — a 37.3% Week-12 clinical remission rate on the selected High dose against a 0.7% placebo rate (+36.6 percentage points; p<0.0001), dose-ordered efficacy corroborated by the continuous modified Mayo analysis and inflammatory biomarkers, and the absence of a dose-dependent safety signal — establish a strong, internally consistent basis for advancing TILA-278 into the confirmatory program described above and for the associated regulatory interactions.

---

Abbreviations: ADA, anti-drug antibody; ANCOVA, analysis of covariance; BLA, Biologics License Application; CDP, Clinical Development Plan; CHO, Chinese hamster ovary; CI, confidence interval; CMC, Chemistry, Manufacturing, and Controls; CMH, Cochran-Mantel-Haenszel; CRP, C-reactive protein; CTD, Common Technical Document; DR3, death receptor 3; DSUR, Development Safety Update Report; EMA, European Medicines Agency; EOP2, End of Phase 2; FAS, Full Analysis Set; FDA, U.S. Food and Drug Administration; HEMI, endoscopic-histologic mucosal improvement; IBDQ, Inflammatory Bowel Disease Questionnaire; IgG1, immunoglobulin G1; IL-22(R), interleukin-22 (receptor); LS, least-squares; MAA, Marketing Authorisation Application; MMRM, mixed-model repeated measures; NRI, non-responder imputation; PBRER, Periodic Benefit-Risk Evaluation Report; PIP, Paediatric Investigation Plan; PK, pharmacokinetics; pp, percentage points; PSUR, Periodic Safety Update Report; Q2W/Q4W, every 2/4 weeks; QTPP, quality target product profile; REMS, Risk Evaluation and Mitigation Strategy; SAE, serious adverse event; SC, subcutaneous; TEAE, treatment-emergent adverse event; TL1A, TNF-like ligand 1A (TNFSF15); TMDD, target-mediated drug disposition; UC, ulcerative colitis.