Jessica Fye

Reshma: differentiation shows in time to ESRD; stronger proteinuria/hematuria/Gd-IgA1 reductions predict better outcomes.

Reshma provided detailed patient population estimates across IgAN (150K), membranous (100K), AMKD (250K), and ADPKD (300K), explaining each targets common rare diseases with transformative potential.

Charlie reiterated top priority is reinvesting in innovation internally and externally, followed by buybacks. Open to all deal types and stages that fit sandbox strategy. Deployed $1.9 billion YTD on share repurchases.

Reshma confirmed the first DPN trial may complete enrollment ahead of the second, with enrollment progressing well.

Duncan cited three factors: payer and P&T progress, positive physician/patient feedback, and strong promotional responsiveness in both face-to-face and digital channels.

Charlie quantified Russia headwind at $100M in Q1 and $200M for the full year, all included in current guidance of 8% growth at midpoint.

Charlie clarified immaterial assessment applies to current tariffs only, citing minimal China exposure and US-based CF manufacturing. Could not size potential sector-specific tariff impact.

Charlie explained US growth benefits from ALYFTREK, JOURNAVX, and CASGEVY launches, while ex-US is impacted by IP violation in one country, most pronounced in Q1.

Charlie declined to quantify but qualitatively cited favorable gross-to-net dynamics in US and one-time VAT rebates and settlements internationally.

Meury quantified the gross-to-net shift and framed the access investment as the right call; Cagnoni gave an early-next-year vitiligo submission timing.

Pablo said ET agreement creates framework for MF. More important issue in MF is primary endpoint: 989 normalizes hematopoiesis, which needs to be contemplated beyond traditional SVR35/TSS50 co-primaries. Constructive FDA dialogue anticipated.

Pablo clarified SVR35 is the key metric. SVR25 reported for directional spleen shrinkage signal, especially with shorter follow-up patients, but SVR35 is what truly matters for regulatory and clinical decision-making.

Pablo outlined framework: safety profile, clinical endpoints in monotherapy, translational endpoints, plus add-on activity in hardest-to-treat patients. Any improvement in suboptimal responders is highly meaningful given low benchmarks (SVR35 9-20%).

Bill emphasized no sacred cows internally and no shiny pennies externally. Doesn't force internal vs external ratio. Goal is to set new highs through growth portfolio (Opzelura, Niktimvo, 989, povo) and BD.

Herve prioritized internal R&D as primary capital allocation, with external BD focused on early-stage research partnerships like Genesis deal. Declined to comment on future share repurchases.

Pablo confirmed roughly directional split of biologic-naive vs exposed. Deferred on powering details and labeling scope, saying they'll wait for data before FDA discussions.

Pablo acknowledged the drop from 28% at week 12 to 17% at week 16 but emphasized week 12 was selected for Phase 3 due to rapid onset. Declined to set specific bar.

Pushkal named two broad buckets, enrollment enrichment and analytic plan changes, but explicitly declined to speculate on alternative approval paths such as a non-inferiority trial.

CCO emphasized AMVUTTRA's growth is driven by fundamental shift toward treating disease at its source, independent of stabilizer pricing dynamics. Category remains significantly underdiagnosed with >80% untreated.

CFO walked through Q4 TTR revenue implied at $850-900M with $125-175M Q/Q growth. Upper end close to Q2/Q3 delivery. Midpoint is most likely Q4 outcome.

CFO walked through math: $1B TTR growth implies $600M+ CM contribution given PN growing ~$300M. Management expressed high confidence in revised guidance based on Q2 momentum.

Management confirmed formulary inclusion goal is year-end completion, with progress running ahead of schedule. Q2 update will include revenue uptake and prescriber metrics.

Management pivoted to market growth narrative and product differentiation but did not address the pricing question despite multiple analysts probing the same topic.

Fye asked what underpins the raised BRINSUPRI peak estimate; Lewis grounded it in a full first year of performance that matched or exceeded internal modeling.

Management explained triangulation methodology using website registrations, institutional prescribing patterns, and internal modeling. On patient metrics, said transparency approach may or may not include patient numbers depending on dynamics.

CEO confirmed key unknowns (market access, refill dynamics, plan changes, reauthorizations, approval rates) are all trending positive versus internal benchmarks. Revenue guidance reflects confidence from these resolved unknowns. Both BRINSUPRI and ARIKAYCE are first-in-disease with no near-term competition.

CEO described net-net positive feedback from CHEST conference physician interactions. COO noted broad prescribing reflects enthusiasm; physicians in trial phase with more severe patients first. Market access experiencing honeymoon period with most prescriptions approved even without formal contracts.

CEO noted other CCOs told him actual results were wildly off from base case. Key factor is patient experience on drug, Phase 2 and 3 showed patients feel better. CFO reminded ~1 month lag from approval to booking revenue.

CEO quantified 250K eligible patients from 500K diagnosed, plus potentially larger comorbid COPD/asthma population.

Berman confirmed Moderna will issue a press release on the interim data; the small seven-patient translational set reflects leukapheresis burden.

Hoge confirmed Q1 delivery was for U.K. spring campaign. Second campaign planned for fall with additional delivery in Q3/Q4.

CFO confirmed U.S. tracking within $1B-$1.3B range. International low end raised to $600M. Canada already delivering, Australia Q4, UK Q1 2026. No UK revenue in 2025, pure growth in 2026.

CFO detailed high end as essentially flat ex-APAs and return adjustments; low end requires 5-10% market share and vaccination rate declines plus international plant licensure delays.

Hoge expressed confidence in no Southern Hemisphere delays. Confirmed CMV readout expected perhaps mid-2025, event-driven.