Vertex Pharmaceuticals (VRTX) investor relations material

Strategic outlook and pipeline priorities

• Focused on execution-rich period through 2026, with expansion in cystic fibrosis (CF), pain, and kidney autoimmune franchises, and advancing multiple late-stage programs.

• CF leadership extended by reaching up to 95% of patients globally, expanding into new geographies and younger age groups, and developing nucleic acid therapies for the remaining 5,000 patients.

• Key late-stage programs include type 1 diabetes cell therapy, diabetic peripheral neuropathy, inaxaplin for APOL1-mediated kidney disease, and POVI for IgAN and membranous nephropathy.

• Capital allocation prioritizes innovation, with 60% of the clinical pipeline from internal R&D and 40% from external sources, highlighted by the Alpine acquisition.

• No plans for dividends; focus remains on reinvestment and stock buybacks as the balance sheet grows.

Cystic fibrosis franchise and next-generation therapies

• Near- and medium-term CF growth driven by new country launches, reimbursement expansion, and approvals for younger age groups.

• ALYFTREK, launched in January 2025, offers once-daily dosing and broader mutation coverage, with conversion rates expected to rise, especially as monitoring requirements differ by region.

• Next-gen correctors VX-828, VX-271, and VX-582 aim to bring more patients below the carrier threshold for sweat chloride, with VX-828 data expected in H2 2026.

• Data suggest further lowering sweat chloride below 30 mmol may not yield additional clinical benefit; focus is on maximizing patient outcomes at this threshold.

• No expectation of further FEV1 improvement beyond current therapies, as lung function gains have reached an asymptote.

Pain, kidney, and autoimmune pipeline updates

• JOURNAVX pain franchise saw over 500,000 prescriptions in 2025, with expectations to triple in 2026, driven by broad adoption in surgical and non-surgical settings and improved reimbursement.

• POVI, a once-monthly subcutaneous biologic for IgAN, is positioned as best-in-class for efficacy and convenience, with a PDUFA date set for November 30 and additional indications in development.

• Inaxaplin phase III (AMPLITUDE) for APOL1-mediated kidney disease completed enrollment, with results expected early next year; phase II studies address modest proteinuria and diabetic cohorts.

• Type 1 diabetes cell therapy in phase III showed 10 of 12 patients insulin-free with excellent glucose control; follow-on programs aim to reduce or eliminate immunosuppression.

• DM1 muscular dystrophy program includes a preclinical small molecule and a phase II oligo-circular peptide asset, with upcoming data focused on splicing and muscle strength.