Salveen Richter

Duncan: strong Rx, 1,400 hospitals/130 IDNs, 2 new Part D plans; PSP bridges remaining access gaps.

Reshma: the blinded DSMB chose 80mg on safety plus RUBY-3 PLA2R reduction; Phase III is enrolling.

Reshma cited Vertex's superior 47.6% proteinuria reduction vs MACE's 35.6% and defended the decision to study homogeneous populations separately rather than mixing heterogeneous groups.

Charlie declined to break down CF guidance between ALYFTREK and other products. Duncan attributed Q4 ALYFTREK strength to European launches in UK, Germany, Denmark, Ireland, Norway, with continued momentum expected into 2026.

Reshma cited strong proteinuria-eGFR correlation in renal diseases, expects it to hold for pove. The medicine with best proteinuria/hematuria/Gd-IgA1 reductions will be best for long-term outcomes.

Reshma outlined step-wise approach: secure DPN first, broaden label through single indications like small fiber neuropathy, then pursue broad PNP potentially with NaV1.7+1.8 combination.

Stuart confirmed fastest ALYFTREK uptake from newly eligible rare mutation patients, followed by discontinued patients returning and TRIKAFTA transitions. Duncan detailed JOURNAVX payer goals of broad coverage with minimal restrictions.

Reshma framed success as ppFEV1 improvement between 3% (ORKAMBI level) and 14% (TRIKAFTA level), noting even 3% translated to 50%+ reduction in pulmonary exacerbations.

Stuart detailed working with national and regional retail chains, expecting broad U.S. availability with product at wholesalers by end of February.

Bradway reiterated a consistent BD strategy focused on smaller, earlier-stage assets in four core areas and said late-stage readouts do not directly gate near-term BD.

Jay explained monthly dosing is already well-characterized in Phase 3; the switch study focuses on less frequent regimens. Murdo added context on switching patients from weekly competitors.

Bradner explained CIDP involves autoantibodies to paranodal proteins in 5-10% of patients, making CD19 B cell depletion a compelling mechanism. Gordon estimated ~35,000 prevalent CIDP patients in U.S. with 7,000-10,000 new diagnoses annually. On Repatha, emphasized VESALIUS-CV data, broad formulary access, and Amgen Now direct-to-patient program as competitive differentiation.

Bradner emphasized best-in-class properties for frequency and depth of Lp(a) suppression but declined to guide on specific readout date. Bradway said restored leverage does not materially change BD approach, focused on earlier-stage opportunities.

Bradway kept comments high-level, saying it was premature to discuss specific proposals. Emphasized need to preserve innovation ecosystem while improving affordability and access.

Gordon described ~20,000 U.S. IgG4 patients, field force deployed for months engaging rheumatologists. Bradner highlighted 87% reduction in disease flares and UPLIZNA's every-6-month dosing advantage in GMG.

Griffith gave a comprehensive breakdown highlighting Repatha, EVENITY, TEZSPIRE, oncology, rare disease and biosimilars as underappreciated growth drivers. Part D redesign described as relatively neutral.

Singhal confirmed proof-of-concept and cited a crowded RRMS market and external BTK inflections, but did not address the safety question directly.

Alisha noted BBM adoption growing rapidly but primarily for triage, not yet confirmation. PCP pilot showing higher BBM usage among educated providers. CMS added BBM for therapy reimbursement confirmation, removing a major barrier. Q1 2026 is when first cohort of Kisunla patients hit 18-month mark. Physicians asking about switching to LEQEMBI maintenance; patients generally want to stay on therapy.

Priya detailed scientific rationale: BDCA2 targets plasmacytoid dendritic cells regulating type 1 interferon. Phase 2 data published in NEJM showed proof of concept in both SLE and CLE. TOPAZ trials use SRI-4 primary endpoint. Inclusion criteria targeted to skin and joint manifestations appropriate for mechanism of action.

Chris cited compelling Phase 2 data across programs: 80% AMR resolution for felzartamab, sustained 2-year IgAN benefit, strong litifilimab Phase 2 in CLE. Noted pipeline has evolved from moonshots to thoughtfully derisked programs. Peak sales potential of late-stage pipeline significant relative to existing business.

Chris outlined shift toward early-stage research collaborations like City Therapeutics to avoid future pipeline gaps. Revamped research organization with lower headcount but different investment approach. Late-stage M&A interest inversely proportional to pipeline confidence. Still looking at assets but increasingly focused on strategic fit and financial discipline.

Chris emphasized blood-based diagnostics could enable earlier treatment initiation. Cited data showing 70% of low-tau patients were stable after six months and 60% showed improvement.

Management detailed significant BD capacity with $2.4B cash, $3B+ EBITDA, and growing free cash flow. Emphasized discipline but said they are always looking at 15-20 projects.

Yancopoulos answered the differentiation question on genetics-driven mechanism but did not size the commercial opportunity as asked.

Schleifer declined to share specifics on competitive grounds, noting the team knows what they're doing and Sanofi has mutual agreement on collaboration.

Yancopoulos said study is powered for PFS matching current combo standard of care at minimum, with OS also powered at that level. Two dose groups being tested. Not using PD-L1 as inclusion/exclusion criteria, population represents true first-line advanced melanoma.

Yancopoulos confirmed GA Phase III is placebo-controlled measuring lesion growth slowing plus vision control. Cohort A results expected second half 2026. Systemic approach has advantages over bilateral intravitreal injections. For novel I&I targets, expects first new program (beyond CD3) to roll out within months with clinical initiation next year.

Schleifer said Regeneron approaches BD with an open mind daily but it's not their lifeline. Developing a metric combining internal R&D and external acquisition spend, arguing Regeneron may not spend much more overall because internal research is so productive. Has flexibility but prefers internal R&D.

Fenimore characterized the CapEx narrowing as minor timing adjustment, confirming full commitment to capital plans with nothing fundamentally changed.

McCourt quantified $85 million favorable EYLEA inventory impact partially offset by lower EYLEA HD inventory. Yancopoulos noted Federal Circuit patent wins may limit biosimilar competition to a single competitor.

Cagnoni described directional strength but gave no target profile numbers, tying the first-line regulatory path to the outcome of second-line FDA discussions.

Pablo explained bispecific binds different CALR epitope, designed for patients who don't respond to 989. V617F program: fully convinced mechanism will work, need to achieve right exposures with solid dispersion formulation. Data expected later this year.

Pablo emphasized three translational endpoints: VAF, CD34+ CALR cells, and malignant megakaryocytes. VAF is lagging indicator; bone marrow reduction is key. Bill expects margins to improve from sales growth and cost control without hard-coding percentage targets.

Pablo explained V617F delay is due to needing higher doses than expected plus longer follow-up, not signal concerns. Bill argued povo is competitive in HS given rapid pain relief, 50%+ clearance rates by week 16-18, and that IL-17s don't work almost half the time.

Pablo framed dual goals: near-term classic endpoints (blood counts, symptoms) plus early allele burden reduction as disease modification evidence. Herve confirmed US patent ownership.

Herve dismissed the week 12-16 drop as trial variability, expressed confidence in powering. Christiana noted Part D savings offset by 340B growth for Jakafi.

Berman declined to disclose statistical powering or interim thresholds and deferred press-release detail until the data is seen.

Hoge explained Stage 1 lung cancer currently treated with surgery alone. INT monotherapy offers IO-like protection with vaccine-like safety profile. Also evaluating combo with KEYTRUDA subcu to prevent Stage 1 from recurring as Stage 4.

CFO split reductions evenly across R&D and COGS. COGS from productivity, R&D from trial wind-downs and selective Phase II/III deprioritization. Also asked about Arbutus IP, Bancel said trial scheduled March 2026, confident in LNP technology.

Hoge explained secondary endpoints will capture virologic measures useful for broader populations including congenital CMV. Intismeran data cadence: Phase III melanoma interim first, then bladder and renal studies in coming 1-2 years.

CFO split reductions evenly across R&D and COGS. COGS from productivity, R&D from trial wind-downs and selective Phase II/III deprioritization.

Hoge described broad endpoint focus including hospitalizations but declined to disclose target product profile or powering assumptions.