Core Insights - Alnylam Pharmaceuticals achieved full-year GAAP profitability in 2025, driven by an 81% year-over-year growth in net product revenues [4] - The TTR franchise generated $858 million in Q4 2025, reflecting a 151% year-over-year increase, primarily due to the U.S. launch of Amvuttra for ATTR cardiomyopathy [4] - Amvuttra has nearly matched tafamidis in new treatment starts by its second full quarter post-launch, indicating a shift in prescribing dynamics [4] Strategic Performance and Platform Evolution - The company launched Cyrillis, a proprietary enzymatic ligation-based manufacturing platform aimed at expanding capacity and reducing costs for RNAi therapeutics [4] - Management attributes commercial success to broad first-line payer access, with over 90% of payers providing coverage without step-through requirements [4] 2026 Guidance and Long-term Strategic Goals - The 2026 TTR revenue guidance is projected between $4.4 billion and $4.7 billion, assuming continued category growth and a mid-single-digit net price decrease in the U.S. [8] - The 2030 strategy aims for a 25% revenue CAGR and 30% non-GAAP operating margins, supported by a pipeline of over 25 clinical programs [4][8] - Planned R&D investment will remain at approximately 30% of revenues to accelerate organic innovation and selectively access external technologies [8] Competitive Dynamics and Pricing Sustainability - Management anticipates a Q1 2026 revenue headwind due to pricing alignment in Germany and annual U.S. insurance reauthorizations [8] - International TTR revenue growth in 2026 is expected to align with 2025, moderated by lower launch pricing for cardiomyopathy in European markets [8] - Collaboration revenue is projected to decline by 38% in 2026 due to a one-time $300 million milestone from the zalesiran program not recurring [8]