Governance & RACI (TILA-278)

Document ID: PM-002
Version: 1.0
Change History: 1.0 — Initial issue.
Standard(s): Program management

Governance & RACI — TILA-278

Decision rights and accountabilities for the TILA-278 programme: the steering committee, the core team roles, escalation paths, and a RACI matrix across clinical, nonclinical, CMC, regulatory, biostatistics, and operations.

1. Purpose and scope

This document defines the governance model and the decision-rights framework for the TILA-278 development programme (Virtual Biopharma Inc.), a recombinant humanized immunoglobulin G1 (IgG1) bispecific monoclonal antibody that couples anti-TL1A (TNFSF15) antagonism with IL-22 receptor (IL-22R) agonism, produced by Chinese hamster ovary (CHO) cell culture and administered subcutaneously (SC) for the treatment of moderate-to-severe ulcerative colitis (UC). It establishes the governance bodies and their remits, the accountable core-team roles, the delegation of authority for stage-gate decisions, the escalation paths, the oversight of the Sponsor's outsourced (virtual) operating model, and a Responsible/Accountable/Consulted/Informed (RACI) matrix spanning the clinical, nonclinical, CMC, regulatory, biostatistics, and operational domains.

The framework governs the transition of the programme from the completed Phase 2b induction study (Protocol TILA278-201) toward a confirmatory Phase 3 programme and marketing application, anchored to the End-of-Phase-2 (EOP2) interaction with health authorities and to a Biologics License Application (BLA) filed under 21 CFR Part 601. It is written to be consistent with the risk-based quality-management and oversight expectations of ICH E6(R3), the quality risk-management principles of ICH Q9(R1), and the biotechnology-specific technical standards that apply to the product (ICH S6(R1) for nonclinical assessment; ICH Q5A(R2), Q5C, and Q6B for viral safety, stability, and specifications). It is the companion governance instrument to the Project Charter (PM-001), the Program Risk Register (PM-004), the Vendor/CRO Management plan (PM-006), and the Clinical Development Plan (PM-007), and it does not restate their content but assigns the decision rights that operate over them.

2. Governance framework

Governance is structured as a four-tier model that separates executive/investment authority from programme-level integration, functional execution, and independent oversight. The tiers are deliberately kept distinct so that benefit-risk and investment decisions are made with the appropriate separation from day-to-day execution, and so that independent safety and data-integrity judgements are insulated from programme advocacy.

• Tier 1 — Executive and Board (investment authority). Approves programme continuation at major stage gates, authorizes the confirmatory-programme investment, and owns portfolio, financing, and partnering decisions for a capital-intensive first-in-class programme. Chaired by the Chief Executive Officer (CEO) with the Chief Business Officer (CBO).
• Tier 2 — Development Governance Committee (DGC) — the steering committee. The standing cross-functional decision body for the programme. It integrates clinical, nonclinical, CMC, regulatory, biostatistics, safety, and operational inputs; endorses the integrated development plan, the target label, and the health-authority strategy; approves benefit-risk positions for external interactions; and is the escalation destination for any risk crossing into the High band of the Program Risk Register. Chaired by the Chief Medical Officer (CMO).
• Tier 3 — Program Team (core team). The operational engine that executes the plan endorsed by the DGC. Led by the Program Director (PMO), it comprises the functional leads and is accountable for delivery to scope, timeline, budget, and quality, and for surfacing risks and decisions to the DGC.
• Tier 4 — Independent oversight. An independent Data Safety Monitoring Board (DSMB) and independent central endoscopy reading provide judgements that are structurally separated from the Program Team. The DSMB reviews unblinded safety data against a pre-agreed charter; central readers apply blinded, adjudicated endoscopy scoring so that the primary and key secondary endpoints are not subject to site-level or Sponsor influence.

Beneath the Program Team, standing functional sub-teams (working groups) execute defined workstreams and report into the core team: a Clinical Sub-team, a Clinical Pharmacology/PK-immunogenicity Sub-team, a CMC/Technical Operations Sub-team (including the combination-product/device workstream), a Nonclinical Sub-team, a Regulatory Sub-team, a Biostatistics and Data Management Sub-team, and a Safety Management Team (SMT) for ongoing signal detection and benefit-risk maintenance.

3. Governance bodies

Table 3-1. Governance bodies, remit, and cadence

Quorum, voting, and conflict-of-interest rules are defined in each body's terms of reference or charter. DGC and Board decisions are minuted with a documented rationale and are traceable to the supporting technical modules of the dossier (Modules 2, 3, and 5). The DSMB operates under an independent charter with a firewalled unblinded statistician; the Sponsor does not access unblinded comparative safety data outside the pre-specified process.

4. Core team roles and responsibilities

Accountable owners are the functional leaders empowered to direct execution within their domain and to escalate. The role key below is used consistently in the RACI matrix (Section 6) and aligns with the ownership taxonomy of the Program Risk Register (PM-004).

Table 4-1. Core team role key and accountabilities

5. Decision rights and delegation of authority

Decision rights are assigned so that each stage-gate has a single accountable authority, a designated recommending body, and defined consulted functions. Recommendations originate in the Program Team and its sub-teams; endorsement of externally facing or benefit-risk-bearing positions rests with the DGC; investment and continuity decisions rest with the Executive/Board.

Table 5-1. Stage-gate decision authority

6. RACI matrix

6.1 Legend and conventions

R — Responsible performs the work. A — Accountable is the single owner who signs off (exactly one A per row). C — Consulted provides input before the decision. I — Informed is notified of the outcome. Governance bodies (DGC) and the PMO appear as columns because they hold integration and endorsement roles distinct from functional execution. The matrix spans the six programme domains named in the scope; where a deliverable is externally facing, the DGC holds an endorsement role and the accountable function retains technical A.

Table 6-1. Programme RACI matrix

7. Escalation

Escalation is triggered by defined thresholds rather than by discretion alone, so that material issues reach the accountable authority without delay. The path runs sub-team → Program Team → DGC → Executive/Board, with independent safety judgements routed through the SMT and DSMB.

Standing escalation triggers include: any Program Risk Register item crossing into the High band or any new Critical-impact risk (to the DGC); a DSMB recommendation to modify, pause, or stop (binding on conduct, with CMO/DGC action); an adjudicated malignancy or proliferative-histopathology safety signal relevant to the IL-22R-agonist mechanism (SMT → DSMB → DGC); a confirmed neutralizing-ADA incidence or exposure attenuation above the pre-specified threshold affecting dose/interval assumptions (HCP → DGC); a CMC comparability-protocol deviation or a specification/stability failure that could affect bridging of the CHO process to commercial scale (VPCMC → DGC); a critical vendor audit finding or GCP data-integrity event (HQA/PMO → DGC); and enrollment or funding shortfalls threatening programme timeline or continuity (PMO/CBO → Executive/Board). Each triggered escalation carries a corrective-action plan with an accountable owner and a defined closure date, and is minuted at the receiving body.

8. Vendor and alliance governance

Virtual Biopharma Inc. operates a largely outsourced model, executing clinical, nonclinical, and manufacturing work through CROs and CDMOs while retaining in-house medical, regulatory, biostatistical, and technical accountability. Governance of this model is therefore explicit: the PMO owns the vendor-governance framework (defined in PM-006), including risk-based monitoring, quality and technical agreements, defined key performance indicators, and a QA audit and inspection-readiness program aligned to ICH E6(R3). CDMO oversight is weighted to the risks specific to a bispecific produced in CHO culture — heterodimer fidelity and product-related impurity control, Protein A capture plus polishing performance, viral safety per ICH Q5A(R2), and comparability across scale — with single-source dependencies tracked as governed risks. Alliance-level decisions (partnering, financing, second-source strategy) are owned by the CBO under Executive/Board authority. Decision rights are never delegated to vendors: recommendations may originate with a CRO or CDMO, but accountability (the A in the RACI matrix) remains with the named Sponsor function.

9. Meeting cadence and reporting

Table 9-1. Governance cadence and reporting flow

Reporting flows upward from the sub-teams through the Program Team to the DGC and Executive/Board, and the risk profile is reconciled by the PMO against the Program Risk Register (PM-004) and the integrated Clinical Development Plan (PM-007) at each cycle. The programme status reflected in this framework corresponds to the completed Phase 2b induction readout from Study TILA278-201, in which clinical remission (modified Mayo ≤ 2, no subscore > 1) at Week 12 was 37.3% (106/284) in the High-dose arm, 16.2% (46/283) in the Low-dose arm, and 0.7% (2/273) on placebo, with dose-ordered key secondary endpoints (endoscopic improvement 48.9% / 27.9% / 6.2%; modified-Mayo LS-mean change −3.36 / −2.76 / −1.00). These results anchor the EOP2 governance decision to advance to the confirmatory programme.

10. Records, interfaces, and document control

Governance records — terms of reference, charters, minutes, decision logs, and the RACI matrix — are maintained under the Sponsor's controlled document system and filed to the Trial Master File and the programme records where GxP-relevant. This framework interfaces directly with the Project Charter (PM-001), the Program Budget and Cost Model (PM-003), the Program Risk Register (PM-004), the Vendor/CRO Management plan (PM-006), and the Clinical Development Plan (PM-007), and it provides the decision-rights layer over the technical assessments held in Modules 2, 3, and 5 of the dossier. It is a living instrument, reviewed at each DGC cycle and updated as the programme advances through the confirmatory phase and marketing-application preparation; changes are version-controlled and reflected in the Change History above.