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- **Revenue Growth**: Q3 2025 revenue $3.08B (+11% YoY), driven by CFTR modulators, ALYFTREK, CASGEVY, and JOURNAVX.
- **CF Breakthroughs**: ALYFTREK covers 95% U.S. CF patients, 50%+ achieve normal sweat chloride. TRIKAFTA 1-2 year-olds show 70% sweat chloride normalization.
- **Pain Innovation**: JOURNAVX reduces opioid use by 90%, CASGEVY nearing $100M annual revenue.
- **Kidney Pipeline**: Pove (IgAN) Phase III interim analysis complete, FDA breakthrough designation granted. Inaxaplin Phase III interim analysis underway.
- **Financial Strength**: Non-GAAP EPS $4.80 (+10% YoY). $12B cash balance, $1.1B Q3 share buybacks.
- **Strategic Expansion**: Building commercial infrastructure for renal portfolio, targeting 150,000+ IgAN patients.

**【CEO Summary Section】**
- **Revenue Growth**: Q3 2025 revenue of $3.08 billion, up 11% YoY, driven by CF franchise expansion, ALYFTREK and TRIKAFTA launches, CASGEVY momentum, and JOURNAVX contributions.
- **CF Portfolio**: ALYFTREK now covers 95% of U.S. CF patients, with 50%+ achieving normal sweat chloride levels. TRIKAFTA 1-2 year-old study shows 70% sweat chloride normalization. VX-828 Phase III underway, targeting even higher efficacy.
- **Pain Franchise**: JOURNAVX prescriptions exceed 300,000, reducing opioid use by 90% in aesthetic surgeries. CASGEVY nearing $100M annual revenue, with 39 patients treated globally.
- **Kidney Pipeline**: Pove (IgAN) Phase III interim analysis complete, FDA breakthrough designation granted. Inaxaplin (APOL1-mediated kidney disease) Phase III interim analysis underway. VX-407 (ADPKD) Phase II proof-of-concept study initiated.
- **Strategic Expansion**: Building commercial infrastructure for renal portfolio, targeting 150,000+ IgAN patients in U.S./Europe. Patient support program extended for JOURNAVX through 2026.

**【CFO Financial Commentary】**
- **Revenue Breakdown**: U.S. revenue +15% YoY, driven by CFTR modulators and ALYFTREK. Non-U.S. revenue +4% YoY, CASGEVY contributing $17M, JOURNAVX $20M.
- **Expenses**: Operating expenses $1.28B (19% YoY growth), driven by pove development and JOURNAVX commercialization. R&D/IPR&D expenses $55M vs. $15M YoY.
- **Profitability**: Non-GAAP EPS $4.80 (10% YoY growth). Cash balance $12B, with $1.1B share buybacks in Q3.
- **Guidance Update**: 2025 revenue $11.9-12B (8-9% growth). Operating expenses $5-5.1B, reflecting pove acceleration. Tax rate revised to 17-18% due to Alpine-related credits.

**【Q&A Highlights】**
- **ALYFTREK Uptake**: 95% of U.S. CF patients now eligible, with 50%+ achieving normal sweat chloride. Europe launch strong, 10x more rare mutation patients than U.S.
- **Pove Differentiation**: Dual BAFF/APRIL inhibition, subcutaneous auto-injector, and tissue-penetrating design. Phase II data shows significant proteinuria reduction, Gd-IgA1 normalization.
- **JOURNAVX Access**: 170M lives covered, 113M unrestricted. Third PBM negotiations ongoing. Patient support program ensures access for 300,000+ prescriptions.
- **Capital Allocation**: Prioritize R&D and commercialization, with $1.9B spent on buybacks YTD. Open to strategic acquisitions aligning with renal and pain franchises.
- **CASGEVY Safety**: Adverse events reported through clinical trials and commercial use, with preconditioning regimen and gene editing data disclosed per regulatory requirements.

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