Ellie Merle

Reshma: for DM1 Phase II she watches splicing plus functional endpoints (vHOT, QMT); likes the oligo circular-peptide cell/nucleus delivery.

Duncan confirmed the year ended at roughly 50/50 retail-hospital split and expects the mix to shift more towards retail. Gross-to-net dynamics depend on prescription duration, patient type (commercial vs Medicaid), and patient support program utilization.

Reshma noted faster-than-expected P&T adoption at large systems. Phase IV trials in plastic surgery and orthopedic conditions showing positive data on pain control and opioid use reduction.

Duncan confirmed 95% retail coverage. Prescription duration averaging about 14 days, consistent with NSAID patterns. Initial prescriptions concentrated in discharge settings as expected while hospital formularies ramp.

Stuart cited ALYFTREK's clinical profile and once-daily dosing as key drivers but could not provide granularity on individual patient reasons for returning.

CMO highlighted nuceresiran, zalesiran (four positive studies), CAA/Alzheimer's, Huntington's, and plasminogen as most de-risked. CFO on pricing: gradual net price reductions expected as business scales, mid-single-digit in year two, with 25% CAGR goal built to incorporate competitive entry.

Management expects both first-line and progressor categories to continue growing but declined to provide specific patient start numbers, citing single-SKU inability to precisely split indications.

Management confirmed single price across PN and CM indications. Quick Start free-dose program seeing limited use as patients are converting to paid therapy quickly across all payer types.

Management declined to break down PN vs CM within TTR guidance. On VBAs, noted ~60% of PN lives covered by value-based agreements and expects carryover to CM.

Hoge said both blinded, event-driven studies with ~300 participants each. Registrational potential preserved. RCC as proof of INT efficacy across tumor types since it differs from melanoma in mutational burden. Timing uncertain, this year or early next.

Hoge estimated European market at ~700M shots. MNEXT Spike competitive profile strong. Combo under review in Europe with potential 2026 approval. European regulators showing appetite for later strain selection, with different strains circulating in U.S. vs rest of Northern Hemisphere.

Dietmar confirmed enrollment on track. Johanna added that a third of PBC patients are partial responders, representing 20,000-25,000 people in US and similar in Europe.