Contract Research Organization (CRO) Oversight Plan

Phase 2 clinical execution under the Master Services Agreement, with obligations transferred by written 21 CFR 312.52 schedule.

SOW-WP1 · Stage 3 · Phase 2 Execution

1 · Parties and Instrument

2 · Scope

This work package covers execution of the Phase 2 study for VTX-401. The Sponsor holds the IND, owns the protocol and carries the safety reporting duty; the CRO runs the study. That division is not a preference — it follows the transfer schedule in section 11, and everything not listed there as transferred remains the Sponsor's.

Phase 2 is where the program learns whether the compound does what the nonclinical package suggested. The commercial consequence is that scope definition matters more here than price: a Phase 2 study that has to be re-run costs the program a gate, not a line item.

In scope. Site identification and qualification for Sponsor approval; site activation and initiation; risk-based monitoring under the agreed model; 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 the clinical study report for this study.

Out of scope. IND maintenance and submissions, which are the Sponsor's as IND holder. Safety reporting to FDA and investigators — the CRO collects and processes, the reporting obligation stays with the Sponsor. Protocol interpretation. Selection of the general investigational plan. Central laboratory and bioanalytical services, contracted separately. Clinical supply manufacture, contracted separately.

Anything not described in this section is out of scope, and under 312.52 anything not listed in the transfer schedule is not transferred. Those two sentences say different things and both apply.

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

Sites identified, qualified and activated before the first participant is approached.

Phase B — Conduct

The study run under the risk-based monitoring model, with data and safety flowing on the agreed cadence.

Phase C — Database lock and report

The study closed out to a locked database and a clinical study report the Sponsor can file against.

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 $22,400,000 for this work package, payable against accepted Deliverables. The rate card annexed to the MSA governs any change order.

• 20% on acceptance of D-W1 — approved site list and activation.
• 40% across the conduct period against accepted D-W2 reporting.
• 20% on acceptance of D-W4 — database lock.
• 20% on acceptance of D-W5 — clinical study report.

⚠ No payment is contingent on a study outcome. A negative result is a correct result, and paying for one differently would corrupt the data the program is buying.

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.

• The protocol is final and approved before start-up begins. An amendment after site activation is a change order priced against the rate card.
• The Sponsor approves the final site list within ten Business Days of submission; activation dates move day-for-day with any delay.
• Clinical supply is available per the separately contracted supply agreement. The CRO ships and accounts for it but does not manufacture it.
• Central laboratory services are available per the separately contracted laboratory agreement.
• The Sponsor's medical monitor is available for safety queries within one Business Day.
• The Stage 3 tranche is released. Work is staged to tranches, and 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.