Alnylam Pharmaceuticals Inc

AMVUTTRA/ATTR cardiomyopathy momentum is strong (and was “surprising” on speed): - Q2 2026 AMVUTTRA/TTR revenues: Alnylam hit first time AMVUTTRA revenues exceeded $1B in a single quarter → > $4B annual run rate only 15 months after U.S. ATTR-CM launch. - Q2 topline performance: Total net product revenues ~$1.2B (+74% YoY); TTR net revenues $1.03B (+89% YoY) and +13% QoQ. - Commercial drivers: Broad access/pull-through, >90% adherence, and growing penetration of prescribers: - ~80% of new AMVUTTRA treatment initiations are first-line (upward importance vs early launch “transition” effects). - AMVUTTRA represents >50% of new patient starts among prescribers already using it, and company added 1,700+ new prescribers since launch through end of Q2.

Guidance cut (bad) but explained as “second-line normalization” (key insight investors should track): - 2026 total net product revenue guidance revised to $4.7B–$5.1B (implies still ~75% YoY growth). - TTR guidance revised to $4.2B–$4.5B, a $200M reduction at the midpoint vs prior outlook. - Management attribution: early 2025 second-line demand had benefited from pent-up demand for a new therapy; as the launch progressed into 2026, second-line volume growth moderated toward a normalized level. - CEO/CFO emphasized they still view the fundamentals as intact, particularly first-line growth; company said it does better in 1st-line than analogs and is investing to expand the prescriber base.

2030 long-term confidence remains, centered on first-line expansion and a more favorable competitive setup (opportunity): - Company reiterated belief in ~25% revenue CAGR through Alnylam 2030 (though the near-term guidance was lowered). - Competitive tailwinds cited: - Anticipate tafamidis U.S. loss of exclusivity in 2031. - Based on eplontersen CARDIO-TTRansform top-line results, company expects fewer branded ATTR-CM competitors in both first-line and stabilizer-progressive segments (supporting AMVUTTRA share capture). - Category growth strategy: investing in diagnosis-enabling initiatives to treat more patients earlier (company estimates ~80% of ATTR-CM patients remain untreated).