Method2Model — Stage-0 Logic Check (Example Deliverable) Dual-Platform ABCD1 mRNA Program for X-Linked Adrenoleukodystrophy (ALD)(LNP + Engineered EVs; Peripheral-first → CNS) This Zenodo record publishes a Stage-0 Logic Check deliverable produced within the Method2Model pipeline, using a dual-platform ABCD1 mRNA therapy concept for X-linked adrenoleukodystrophy (ALD) as a real-world example. Stage-0 is designed to sit before Stage-1 (Assumptions Map + Architecture). It is a compact, decision-oriented review that prevents teams from entering modeling or wet-lab execution with undefined success criteria, unlocked decision gates, and hidden “first-break” assumptions. What Stage-0 Delivers (site-aligned outputs) This record includes the three core Stage-0 outputs: Feasibility Note: Yes / Yes with changes / Not a fit now (with brief rationale) Use-Case Selection: recommendation of 1–2 best-fit Method2Model use cases (plus secondary set if needed) Minimum Inputs List: the minimum information required to start Stage-1 without ambiguity What’s Inside the Stage-0 Deliverable The PDF deliverable includes: Verdict (Executive): scope/non-scope and feasibility verdict Project Feedback: what we understood from the client materials “First-break” expectation: what is most likely to fail first if something breaks Decision-Risk Map (standardized): bottlenecks with Impact/Evidence ratings and “what data changes the decision (minimum)” Gap-Closing Questions: prioritized as Question → Why it matters → Expected artifact Minimum Inputs List (Stage-1 intake): decision rules, endpoint hierarchy, assay variance basics, EV potency definition, regimen candidates, safety policy basics, and constraints Stage-1 readiness criteria: the minimum lock-ins required to start Stage-1 defensibly Note: Any numeric targets referenced are treated as proposed decision gates pending formal lock-in during Stage-1. Files in This Record ALD_mRNA_Therapy_Stage_0_Output.pdf — Stage-0 Logic Check deliverable (review-ready) ALD_mRNA_Therapy_Stage_0_Output.tex — LaTeX source for transparency, reuse, and adaptation Inputs Reviewed (as provided) This assessment is based on client-provided materials only (concept proposal, aims, endpoint checklist, draft question bank). It includes no independent verification of underlying claims, methods, or datasets. Intended Use and Disclaimer This record is intended to support research planning and modeling readiness. It is not medical advice and does not replace regulatory, clinical, or safety governance. License / Use This deposit is intended for research and educational use. For commercial use, redistribution, or inclusion in a paid deliverable, please follow the license terms listed on the Zenodo record and/or obtain permission from Method2Model. How to Cite Please cite this Zenodo record: DOI: 10.5281/zenodo.18074005 Contact Name: Dr. Ramyar Azar Role: Founder, Method2Model Email: drazar@method2model.com Website: https://method2model.com/ Stage-0 is where ambiguity is removed, “first-break” risks are surfaced, and Stage-1 becomes defensible, before time, budget, animals, or patients are committed.