# Stage 13 — CPT:PSP Submission Package Report
**Model:** ASMD/Xenpozyme QSP v2.0
**Target journal:** CPT: Pharmacometrics & Systems Pharmacology

## Files produced

| File | Format | Purpose |
|---|---|---|
| `ASMD_Xenpozyme_QSP_v2_0_cover_letter.docx` + `.pdf` | DOCX + PDF | Editor-in-Chief cover letter |
| `ASMD_Xenpozyme_QSP_v2_0_manuscript_CPTPSP.docx` + `.pdf` | DOCX + PDF | Reformatted manuscript |
| `ASMD_Xenpozyme_QSP_v2_0_supplementary_index.docx` + `.pdf` | DOCX + PDF | Supplementary materials index (S1–S11) |

## CPT:PSP submission readiness

The manuscript follows the CPT:PSP author guidelines:
- **IMRAD format**: Abstract, Introduction, Methods (4 subsections), Results (4 subsections), Discussion, Conclusion
- **Continuous prose**: minimal bullet usage; bullets reserved for the cover letter's contribution list
- **Vancouver references**: 39 references R1–R39 in the separate landscape table
- **Funding, Conflicts of Interest, Data and Code Availability**: each as a labelled section
- **Open licensing**: MIT/CC-BY-4.0 dual-licence statement included
- **Word count target**: ~5500 words (within CPT:PSP 6000-word limit for original research)

## Cover letter highlights

The cover letter emphasises four novel contributions:

1. First mechanistic QSP model jointly calibrated on adult + paediatric olipudase alfa data with regulatory-grade ASME V&V40-2018 documentation (G1–G10 PASS or PASS-CONDITIONAL).
2. Hierarchical Bayesian random-effects meta-analysis (PyMC NUTS) yielding pooled estimates inside the 94 % HDI of the v2.0 model on every analysed endpoint.
3. Saturation as the structural mechanism for the absence of dose-response gradients above 3 mg/kg q2w in ASCEND-OLE — quantitative argument against further dose-escalation studies.
4. Cross-population coherence of GSA dominance pattern between adult and paediatric, supporting unified parameter framework with paediatric overrides — relevant to ICH E11(R1).

## Supplementary materials index (S1–S11)

The supplementary index documents 11 content groups: SBML files, synthetic data, calibration, V&V, GSA, identifiability, Bayesian, combination, master figures, regulatory artefacts, and reproducibility notes. Total package: ~70 files in 14 stage directories.

**Stage 13 status: COMPLETE — proceed to Stage 14 ATLAS web page.**
