Gate Decision Framework

Program timeline · status Oct 15, 2026Read the full story →

Gate 0

Mar 2022

Stage 1

Nonclinical

Gate 1

Dec 2022

Stage 2

Investigational New Drug application (IND) & Phase 1

Gate 2

Jun 2023

Gate 3

May 2024

Gate 4

Jun 2026

Go w/ conditions

Stage 4

Phase 3

Gate 5

Sep 2028

Gate 6

Oct 2029

Launch

Nov 2029

Vitalis Therapeutics Inc. — The criteria against which every gate in the VitaFlow (VTX-401) program is decided: the two-tier must-meet and should-meet model, the scoring scale, the evidence standard, and the full criteria set for all seven gates. Operates alongside the Development Committee Charter, which defines who decides.

Gates

Criteria tiers

Threshold score

Possible outcomes

Contents

The Two-Tier Model
Scoring Scale
Evidence Standard
Gate Criteria
How an Outcome Is Derived
Worked Example — the Gate 4 Score Sheet
What a RECYCLE Would Have Looked Like
Evidence Packs
Criteria Change Control

1. The Two-Tier Model

Every gate assesses two kinds of criteria, and they behave differently on purpose.

Tier	Nature	Effect of a shortfall
Must-meet	Binary. Satisfied or not.	An unsatisfied must-meet cannot produce a GO. The outcome is RECYCLE if remediable, KILL if not. It is not outvotable — a majority cannot vote a criterion into satisfaction.
Should-meet	Scored 1–5 against a defined scale.	Scores at threshold (3) produce conditions. Scores below threshold drive RECYCLE. Scores at 4 or 5 carry no consequence.

Why the tiers are separated. A single blended score lets a strong commercial case compensate for a weak safety package. Separating them prevents that arithmetic: no amount of commercial upside converts an unsatisfied must-meet into a pass, because the two tiers do not share a scale.

2. Scoring Scale

Score	Meaning
5	Fully satisfied. Evidence complete and independently verifiable.
4	Satisfied. Minor gaps that do not affect the decision.
3	Threshold. Satisfiable inside the next stage — the score that produces a condition rather than a failure.
2	Materially short. Drives RECYCLE unless a must-meet is also unsatisfied.
1	Absent. No credible evidence tabled.

The threshold score is 3. It is deliberately defined as “satisfiable inside the next stage” rather than “adequate”, because the question a gate asks about a should-meet criterion is not whether the position is good — it is whether the gap can be closed with work the program is about to do anyway.

3. Evidence Standard

A criterion is assessed on evidence tabled at the gate, not on assurance given at the gate. The Chair certifies that what has been tabled meets the standard; the Committee decides what it means.

Acceptable	Not acceptable
Signed reports, agency minutes, validated datasets	Verbal summary of a report not yet issued
Executed contracts and dated commitments	Draft agreements and expressions of intent
Data from the running study	Extrapolation from an earlier phase
Independent verification where the criterion is contested	Self-assessment by the owning function alone

Assertion is not evidence. “The team is confident enrolment will recover” is an assertion. A site activation schedule with dated commitments and a screen-failure rate from the running study is evidence. Where only assertion is available, the criterion scores 1 — not 3 with a caveat.

4. Gate Criteria

Criteria are set when a gate is defined and are not revised inside the stage that leads to it. A criterion the program discovers it cannot meet is a matter to escalate, not a matter to rewrite.

Gate 0 — Candidate Selection — Mar 1, 2022 · GO (6-0)

Must-meet

Ref	Must-meet criterion	What decides it
M1	Target validated in at least two independent models	Two published or internal models, different modalities, both showing the effect. One model is a hypothesis.
M2	Freedom-to-operate opinion obtained	Written opinion from counsel on record. Not a database search.
M3	Candidate meets the minimum target product profile	Every minimum attribute in the Target Product Profile (TPP) met. Aspirational attributes may be unmet.

Should-meet

Ref	Should-meet criterion	Score	Why that score
S1	Differentiation against approved products in the class	4	Plausible advantage on at least one axis a payer recognizes; not yet demonstrated head-to-head, which is what holds it at 4.
S2	Projected development cost within portfolio tolerance	4	Within the band at the point estimate; the downside case exceeds it.
S3	Commercial case supports the therapeutic area	5	Category economics independently established; not contingent on this asset.

Gate 1 — IND-Enabling Readiness — Dec 31, 2022 · GO (5-1)

Must-meet

Ref	Must-meet criterion	What decides it
M1	GLP toxicology package complete and supportive of first-in-human	Repeat-dose studies in two species to GLP, with a defined no-observed-adverse-effect level supporting the proposed starting dose.
M2	Drug substance route defined and reproducible at scale	Three consecutive batches to specification at the intended scale. Two is a coincidence.
M3	Regulatory strategy agreed and pathway confirmed	Pathway confirmed in writing at the pre-IND meeting, not inferred from precedent.

Should-meet

Ref	Should-meet criterion	Score	Why that score
S1	Analytical methods qualified	3	Qualified, not validated. Validation is a Gate 3 expectation; holding this at 3 records that the gap is known rather than missed.
S2	Drug product formulation stable to the required shelf life	4	Accelerated data supports it; real-time data does not exist yet and cannot.
S3	Clinical development plan costed and resourced	4	Costed to a defensible basis; resourcing depends on a hiring plan not yet executed.

Gate 2 — IND Submission — Jun 30, 2023 · GO (6-0)

Must-meet

Ref	Must-meet criterion	What decides it
M1	IND submitted and accepted — thirty-day review clear	Thirty days elapsed with no clinical hold. Silence is the approval.
M2	Phase 1 protocol final and IRB-approved	Approved at the conducting site, with the consent form version recorded.
M3	Clinical supply released to specification	Qualified Person release against the specification, with a certificate of analysis.

Should-meet

Ref	Should-meet criterion	Score	Why that score
S1	Investigator sites contracted	4	Contracts executed at the sites needed for the first cohort; later cohorts in negotiation.
S2	Pharmacovigilance system operational	5	Safety database live, case processing tested end to end, reporting clocks configured.

Gate 3 — Phase 2 Readiness — May 31, 2024 · GO (6-0)

Must-meet

Ref	Must-meet criterion	What decides it
M1	Phase 1 safety and tolerability support continued development	No dose-limiting toxicity at the doses intended for Phase 2, adjudicated by the medical monitor rather than asserted by the program.
M2	Pharmacokinetic profile supports the intended dosing interval	Exposure sustained across the dosing interval in the majority of participants at the intended dose.
M3	Phase 2 protocol final, dose span justified	Dose span bracketing the predicted effective dose, justified from Phase 1 exposure rather than chosen for convenience.

Should-meet

Ref	Should-meet criterion	Score	Why that score
S1	Analytical methods validated and transferred	4	Validated at the sending site; transfer to the receiving site in progress.
S2	Chemistry, Manufacturing and Controls (CMC) capacity adequate for Phase 2 supply	4	Capacity confirmed for planned enrolment with no allowance for over-enrolment.
S3	Competitive landscape unchanged in a material way	3	Two competitor readouts fall inside the Phase 2 window, so this cannot be held higher with honesty.

Gate 4 — Phase 3 Initiation — Jun 30, 2026 · GO WITH CONDITIONS (5-0-1)

Must-meet

Ref	Must-meet criterion	What decides it
M1	Phase 2 efficacy demonstrated at a dose with acceptable tolerability	Primary endpoint met with statistical significance at a dose whose discontinuation rate is tolerable in chronic use.
M2	End-of-Phase-2 meeting held; pivotal design and endpoints agreed with the agency	Official minutes issued, recording agreement on the co-primary endpoints. Minutes, not the sponsor's note of the meeting.
M3	Phase 3 protocol final and statistically powered to the agreed endpoints	Power calculated at the pre-agreed level for both co-primaries, on the agreed analysis population.
M4	Manufacturing plan supports registration-batch timing	Registration batches scheduled to complete before the submission date with float that survives one failed batch.

Should-meet

Ref	Should-meet criterion	Score	Why that score
S1	CMC readiness — analytical method transfer complete	3	Transfer in progress at the commercial site. Held at 3 deliberately: this is the criterion most likely to move the filing date, and it is the weakest.
S2	Market access evidence plan in place	3	Plan exists; the payer evidence it calls for is not yet being collected, which is a cost of the Phase 3 design being fixed first.
S3	Phase 3 site and enrolment plan credible against the curve	4	Site count and activation rate support the curve at planned productivity; no allowance for the activation slippage that later became I-01.
S4	Business case clears the hurdle on refreshed assumptions	4	Clears at the point estimate; sensitivity on price erosion brings it close.

Three should-meet criteria scored 3 at Gate 4 — CMC method transfer, market access evidence, and (at 4) the enrolment plan. The two scored at threshold produced GC-01 and GC-03. This is the framework working as designed: the gate carried, and the two weakest areas were converted into dated, owned, verifiable obligations rather than absorbed as optimism.

Gate 5 — New Drug Application (NDA) Submission — Sep 30, 2028 · pending

Must-meet

Ref	Must-meet criterion	What decides it
M1	Both pivotal trials met the co-primary endpoints	Both co-primaries met in both trials, on the pre-specified analysis, against the locked database.
M2	Safety database complete and integrated summaries drafted	All events coded and reconciled; integrated summaries drafted against the final dataset rather than an interim extract.
M3	Registration batches manufactured, on stability, process validation complete	Three batches released, on stability, with process performance qualification complete. This is the criterion that most often moves a filing date.
M4	Pre-NDA meeting held and content agreed	Minutes recording agreement on submission content and format, so the application cannot be refused for structure.

Should-meet

Ref	Should-meet criterion	Score	Why that score
S1	Labeling strategy aligned to the data	not yet assessed	Assessed at the gate: the label sought must be supported by the data obtained, not by the data hoped for.
S2	Launch supply plan credible against the action date	not yet assessed	Supply must be releasable before approval, because approval does not wait for it.
S3	Payer evidence package complete	not yet assessed	Complete enough to open coverage discussions at launch, not to conclude them.

Gate 5 is the next gate. Should-meet criteria are recorded but not yet scored; scoring happens at the gate on evidence tabled, not in advance. Open items carried against them are tracked in the Gate Conditions Register, and live position against every criterion is maintained in the Gate 5 Readiness Assessment.

Gate 6 — Approval & Launch — Oct 11, 2029 · pending

Must-meet

Ref	Must-meet criterion	What decides it
M1	Approval granted	Approval letter received. Nothing about this criterion is within the program's control, which is why it is a gate rather than a milestone.
M2	Pre-approval inspection closed with no unresolved deficiency	Any observations responded to and accepted. An open observation blocks launch regardless of the clinical package.
M3	Launch supply released and in distribution	Released against the approved specification and physically in the channel.

Should-meet

Ref	Should-meet criterion	Score	Why that score
S1	Field force trained and deployed	not yet assessed	Trained on the approved label only. Training ahead of the label risks promoting beyond it.
S2	Payer coverage secured in the launch accounts	not yet assessed	Coverage in the accounts that carry the launch volume, not coverage in aggregate.

5. How an Outcome Is Derived

Assess must-meets first. If any is unsatisfied, the outcome is RECYCLE or KILL and the should-meet scoring is not reached. This ordering matters: scoring first invites the committee to weigh a strong overall picture against a specific unmet obligation.
Score should-meets against §2, on evidence per §3.
Derive the outcome. All must-meets satisfied and no should-meet below 4 → GO. All must-meets satisfied with one or more should-meets at 3 → GO WITH CONDITIONS, one condition per criterion at threshold. Any should-meet at 2 or below → RECYCLE.
Record. The score sheet is part of the minutes and is not amended after approval.

The outcome is derived, not negotiated. The Committee's judgment is exercised in the scoring — which is where judgment belongs — not in the step from scores to outcome. Once the scores are recorded the outcome follows mechanically, which is what stops a gate from becoming a negotiation about how much the program would like to proceed.

6. Worked Example — the Gate 4 Score Sheet

The framework above describes machinery. This section runs it, using the actual Gate 4 decision of Jun 30, 2026.

Step 1 — Must-meet assessment

Ref	Criterion	Evidence tabled	Assessment
M1	Phase 2 efficacy demonstrated at a dose with acceptable tolerability	Locked Phase 2 dataset; primary and secondary endpoint analyzes; discontinuation rates by dose arm	satisfied
M2	End-of-Phase-2 meeting held; pivotal design and endpoints agreed with the agency	Official minutes, May 19, 2026; agreed co-primary endpoints; CV safety expectation recorded	satisfied
M3	Phase 3 protocol final and statistically powered to the agreed endpoints	Final protocol v1.0; statistical analysis plan; power calculation at 90% for both co-primaries	satisfied
M4	Manufacturing plan supports registration-batch timing	CMC plan with registration-batch schedule; Aldergate capacity confirmation	satisfied

All four satisfied. The gate proceeds to scoring. Had any been unsatisfied, scoring would not have occurred — the ordering at §5 exists precisely so that a strong overall picture cannot be weighed against a specific unmet obligation.

Step 2 — Should-meet scoring

Ref	Criterion	Score	Basis
S1	CMC readiness — analytical method transfer complete	3	Two of three methods re-qualified at Aldergate; the third in progress with a dated plan. Closeable inside Stage 4, so threshold rather than below.
S2	Market access evidence plan in place	3	Evidence plan drafted; payer advisory board program scoped but not scheduled. Work identified, not started.
S3	Phase 3 site and enrolment plan credible against the curve	4	Site list with activation sequence and a reserve list; recruitment rates carried forward from Phase 2 with a stated haircut.
S4	Business case clears the hurdle on refreshed assumptions	4	Refreshed model returns 43.6% against a 15.0% hurdle. Minor gap: gross-to-net assumptions not re-tested against the latest payer landscape.

Step 3 — Outcome derivation

All must-meets satisfied; two should-meets at threshold. Per §5 the outcome is GO WITH CONDITIONS, with one condition per criterion at threshold. Nothing here is a judgment call at this step — the judgment was exercised in the scoring.

Threshold criterion	Condition issued	Owner	Due
S1 — CMC method transfer	GC-01 — complete re-qualification for all three methods	Dr. K. Oyelaran	Dec 18, 2026
S2 — Market access evidence	GC-03 — stand up the payer evidence plan and hold first advisory boards	J. Barrington	Mar 31, 2027

GC-02 was also issued at this gate, but not from a threshold score — it arose from the CR-02 scope addition approved shortly before, and attaches the (Independent) Data Monitoring Committee (DMC) protocol confirmation to the sub-study. Conditions may be issued for reasons other than a threshold score; a threshold score must always produce one.

Step 4 — The vote

Recorded outcome: GO WITH CONDITIONS (5-0-1). Five voting seats, four in favour, one abstention. The abstention was recorded by the Chief Financial Officer against S4 — specifically the un-refreshed gross-to-net assumptions — on the basis that a $125,800,000 release warranted a fully re-tested commercial model rather than one with a stated minor gap.

The abstention was not overruled and did not block the gate. It is part of the permanent record, and it is the reason the business case refresh carries a standing item at Gate 5. An abstention is a statement that a member cannot support the decision on the evidence tabled — recording the reason is what makes it useful eighteen months later, when the question of whether the commercial case was tested becomes live again.

7. What a RECYCLE Would Have Looked Like

Gate 4 carried. It is worth setting out what the same gate would have produced had the evidence been weaker, because a framework is only meaningful if the failure paths are as well defined as the success path.

Scenario — M1 unsatisfied

Suppose the Phase 2 dataset had shown efficacy at the top dose but with a discontinuation rate materially above the modelled figure, such that no dose demonstrated efficacy with acceptable tolerability. M1 is then unsatisfied.

Step	What happens
Scoring	Does not occur. The must-meet assessment terminates the gate.
Outcome	RECYCLE — the criterion is unsatisfied but remediable: an extended dose-escalation schedule is work the program can actually perform.
Tranche	The $125,800,000 Stage 4 tranche does not release. Phase 3 does not start, and no Contract Research Organization (CRO) Phase 3 work package is authorized.
Remediation scope	Chair produces it within ten working days: a tolerability sub-study on a revised escalation schedule, its cost, its owner, and the date Gate 4 re-convenes.
Funding	From contingency, against a named draw. The cost of the recycle is therefore visible in the Program Budget rather than absorbed.
Roster	Retained. Releasing and rebuilding a 109-person program team costs more than carrying it through a remediation window.
Agency	The End-of-Phase-2 position may require revisiting, since dose selection was agreed on the superseded data. This is usually the longest pole in a recycle, not the clinical work itself.

Why this scenario matters more than the one that happened. A committee with no RECYCLE option facing an unsatisfied M1 has two usable choices: pass anyway on an understanding that tolerability will be managed in Phase 3, or kill an asset that has cleared every other criterion. It will choose to pass, and the program will discover in Phase 3 — at $125,800,000 rather than at the cost of a sub-study — what it could have learned first.

8. Evidence Packs

Each criterion is assessed on a defined evidence pack, submitted at day −20 per the gate preparation timetable in the Development Committee Charter. Pack contents are fixed when the gate is defined.

Gate	Evidence pack contents
Gate 0	Target validation data from two independent models; freedom-to-operate opinion; target product profile; indicative development cost and timeline.
Gate 1	GLP toxicology study reports; drug substance route and reproducibility data; formulation stability data; regulatory strategy document; costed clinical development plan.
Gate 2	IND submission receipt and thirty-day clearance; final Phase 1 protocol with IRB approvals; certificate of analysis and release documentation for clinical supply; executed site contracts; pharmacovigilance system master file.
Gate 3	Phase 1 clinical study report; PK/PD analysis; final Phase 2 protocol with dose justification; site activation plan; CMC supply plan for Phase 2.
Gate 4	Locked Phase 2 dataset and analyzes; End-of-Phase-2 official minutes; final Phase 3 protocol and statistical analysis plan; power calculation; CMC plan with registration-batch schedule; refreshed business case model; site and enrolment plan.
Gate 5	Clinical study reports for both pivotals; integrated summaries of safety and efficacy; registration-batch release and stability data; process validation report; Pre-NDA meeting minutes; draft labeling; launch supply plan.
Gate 6	Approval letter; pre-approval inspection close-out; batch release documentation; distribution readiness confirmation; field deployment and training records; payer coverage position in launch accounts.

A pack is a list of documents, not a presentation. Slides may be used to walk the Committee through the pack; they are not themselves evidence, and a criterion supported only by a slide is supported only by assertion (§3).

9. Criteria Change Control

Criteria are set when a gate is defined and are not revised inside the stage leading to it.

A criterion may be added at any time by Committee decision, minuted, where a new obligation arises — a regulatory expectation, a change in the competitive or safety landscape.
A criterion may not be removed or weakened inside the stage that leads to the gate it governs. Removal requires a Committee decision taken at least one full stage before the gate, which makes it impossible to remove a criterion the program is currently failing.
Evidence-pack contents may be clarified but not reduced. A clarification specifies what form evidence must take; a reduction changes what must be shown.
Every change is recorded with the date, the rationale, and the gate from which it takes effect.

The one-stage rule is the whole provision. Without it, a program approaching a gate it will not pass has an obvious and entirely rational move: propose a criteria revision. The revision will be well-argued, the reasoning will be sound, and the gate will be rendered meaningless. Requiring a full stage of separation removes the option at exactly the moment it becomes tempting.