Contract Research Organization (CRO) Oversight Plan

Both pivotal Phase 3 studies and the cardiovascular sub-study, under the Master Services Agreement and the 312.52 transfer schedule.

SOW-WP2 · Stage 4 · Phase 3 Execution — Both Pivotals and CV Sub-Study

1 · Parties and Instrument

2 · Scope

This work package covers both pivotal Phase 3 studies and the cardiovascular sub-study. It is the largest commitment in the program at $68,500,000 — 73% of the total Meridian contract — and the one whose failure cannot be recovered inside the program's schedule.

Scale changes what matters. At Phase 2 the risk is that the study answers the wrong question; at Phase 3 the risk is that it answers the right question badly, across hundreds of sites, in a way that is not visible until database lock. The monitoring model, the query cycle and the reconciliation cadence in this package exist to make problems visible early rather than at the end.

In scope. Site identification and qualification for Sponsor approval across both pivotals and the sub-study; activation and initiation; risk-based monitoring; investigational product shipment and accountability; data management and query resolution; safety data collection and processing for onward Sponsor reporting; trial master file maintenance with Sponsor right of access; and a clinical study report for each study.

Out of scope. IND maintenance and submissions. Safety reporting to FDA and investigators. Protocol interpretation. NDA authorship and submission, which is the Sponsor's. Central laboratory and clinical supply, contracted separately.

Anything not described in this section is out of scope, and anything not listed in the transfer schedule is not transferred.

3 · Approach

The work package is executed against the transfer schedule in section 11 rather than against custom. The CRO performs what has been transferred, the Sponsor performs what it retained, and where an obligation is shared the split is stated rather than assumed.

Reporting is designed so that a problem is visible before it is expensive. Enrollment, monitoring completion and query age are reported on a fixed cadence, and protocol deviations are reported as a compliance obligation rather than a service level — the distinction matters, because a service level invites a tolerance band and a compliance obligation does not.

SAE reconciliation is the one measure with no tolerance at all. Completeness is 100% or it is a finding. A reconciliation that is 98% complete is not 98% good; it means two percent of the safety picture is unaccounted for, and neither party can say which two percent.

Audit and inspection readiness is continuous rather than prepared for. The Sponsor retains right of access to trial records at any time, without notice, and the CRO maintains them accordingly.

4 · Delivery Phases

Phase A — Start-up across both pivotals

Sites qualified and activated at scale, with the sub-study's additional requirements handled at qualification rather than after.

Phase B — Conduct at scale

Both studies and the sub-study run concurrently, reported so that a problem in one is visible without reading three reports.

Phase C — Lock and reporting

Each study locked and reported to a standard the NDA can be built on.

5 · Acceptance

Each Deliverable is submitted with the evidence its acceptance criteria call for. The Sponsor has the stated Review Period to accept, or to reject in writing with specific, criterion-by-criterion reasons. Silence for the whole Review Period is acceptance — deemed acceptance.

⚠⚠ Deemed acceptance applies to deliverable documents only. It does not apply to any obligation the transfer schedule retains for the Sponsor, and it does not apply to SAE reconciliation: completeness is 100% or it is a finding, which leaves no tolerance band for silence to run against. Protocol deviation reporting is likewise a compliance obligation rather than a service level, and does not become acceptable by the passage of a review period.

6 · Timeline and Resourcing

Work packages are released by notice at the gate opening their stage, and work is staged to tranches: an unreleased tranche is not authority to proceed. The table below shows who is involved on each side. Sponsor effort is not charged under this Statement of Work; it is shown because the CRO's obligations depend on it, and because several of these roles hold duties the transfer schedule explicitly retains.

7 · Price and Payment

Fixed price of $68,500,000 for this work package, payable against accepted Deliverables. The rate card annexed to the MSA governs change orders.

• 15% on acceptance of D-P1 — site lists and activation.
• 45% across the conduct period against accepted D-P2 reporting.
• 20% on acceptance of D-P4 — database lock, all studies.
• 20% on acceptance of D-P5 — clinical study reports.

⚠ No payment is contingent on a study outcome, and none is contingent on enrollment rate. Paying for speed at Phase 3 buys enrollment the protocol did not intend.

8 · Assumptions

The price and the stage schedule rest on the following. Each is stated so that its failure is visible rather than argued about later; where one fails, the consequence is handled under Change Orders.

• Both protocols and the sub-study protocol are final before start-up. An amendment after activation is a change order against the rate card.
• The Sponsor approves site lists within ten Business Days per study.
• Clinical supply and central laboratory services are available per their separate agreements; a shortfall in either is outside the CRO's control and is handled under Change Orders.
• The Sponsor's medical monitor is available within one Business Day for safety queries across all studies.
• Reporting is per study throughout. The CRO does not merge study data into a single status figure.
• The Stage 4 tranche is released. An unreleased tranche is not authority to proceed.

9 · Change Orders

Either party may propose a change order. The CRO prices it against the rate card annexed to the MSA within ten Business Days, stating the effect on price, on the stage schedule, and on any other Deliverable. No change order takes effect until both parties sign.

⭐ Fixed price does not mean the Sponsor has stopped carrying risk — it means the Sponsor has concentrated its risk in scope definition. The program has approved four change orders totaling $3,100,000 against these work packages, with one further in dispute. That is the model working rather than failing: each one marks a place where the Sponsor's scope moved, and the fixed price made the movement visible and priced. A time-and-materials contract would have absorbed the same changes silently.

⚠ A change that would alter which regulatory obligations are transferred is never a change order. It requires an amended written transfer under 312.52 — the schedule is not a commercial term to be traded.

10 · Terminology

11 · Transfer of Regulatory Obligations (21 CFR 312.52)

This Statement of Work is accompanied by a written transfer of obligations under 21 CFR 312.52. The schedule below states which duties moved and which did not.

⚠ The default is retention. An obligation not written down is not transferred — however clearly both parties believed otherwise, and however competently the CRO has been performing it. That inverts ordinary commercial intuition, where an ambiguity is a negotiation whose answer depends on the contract's construction. Here the answer is fixed in advance and it is always the same: silence means the Sponsor kept it.

The corollary matters equally. Under 312.52(b) a CRO that assumes an obligation becomes subject to the same regulatory action as a Sponsor for failing it. Transfer is real; it is simply not implicit, and it is not a way of making a duty disappear.

12 · Governing Agreement

This Statement of Work is issued under the Master Services Agreement and creates no rights independent of it. Warranty, limitation of liability, intellectual property, confidentiality, insurance, indemnity and dispute resolution are governed by the MSA and are not restated here. Restating them invites the two documents to disagree.

Three instruments prevail over this Statement of Work on the matters they address: the written transfer of regulatory obligations under 312.52; the Pharmacovigilance Agreement, on safety data exchange; and the Quality Agreement where investigational product handling is engaged. The rate card annexed to the MSA governs change orders. Where this SOW and the MSA conflict on commercial terms the MSA prevails; on scope, deliverables and acceptance, this SOW does.

13 · Approval

⚠ A gate outcome is a Committee decision, minuted, and is not subject to reversal by any individual member including the Executive Sponsor. This work package is released against that decision; the table below records it rather than replacing it with signatures. The Program Director chairs and does not vote.