Alnylam Pharmaceuticals, Inc. (ALNY) Earnings

Management highlights

- Commercial Launch & Market Position * Amvutra's ATTR cardiomyopathy launch is exceeding industry benchmarks, with 80% of new treatment starts now in the first-line setting, the company's core strategic focus. Adherence exceeds 90% and access remains broad with no meaningful reimbursement headwinds. * Over 1,700 new Amvutra prescribers have been added since launch, with Amvutra representing over 50% of new patient starts among existing prescribers, demonstrating strong physician preference. The company is intensifying investment to expand the prescriber base, as only ~1/3 of eligible TTR prescribers have experience with Amvutra. * The company announced an exclusive commercialization and distribution collaboration with B1 for Amvutra in Mainland China and Macau, pending marketing approval, to expand geographic access in an underserved market. * An estimated 80% of ATTR-CM patients remain untreated, and overall category growth is accelerating, driven by improved diagnosis and awareness initiatives. - Research & Development * Management maintains full confidence in the Nucreceran (Nucresiran) Phase III Triton-CM outcomes trial, despite the recent negative top-line result of competitor AstraZeneca's CardioTransform study of Eplon-Tersen. Confidence is grounded in fundamental differences between RNAi (Alnylam's platform) and antisense oligonucleotide (competitor) molecules, Nucreceran's best-in-class projected >95% TTR knockdown with low variability, optimized study design, and Alnylam's 15+ years of TTR development experience. The company will review full CardioTransform data and may adjust the Triton-CM protocol if needed. * New Phase II trials were initiated for ALN6400 (von Willebrand's disease / hereditary hemorrhagic telangiectasia) and Mivalceran (Down syndrome associated Alzheimer's disease) in the quarter. Four key data readouts are expected in H2 2026, including initial Phase 1 data for ALN-HTTO2 (Huntington's disease) at EHDN in October, and Phase 1/Phase 2 data for ALN2232 (obesity/weight management). * Nucreceran is on track for a projected 2028 launch in HATTR polyneuropathy (pending positive Phase III data and approval) and 2030 launch in ATTR cardiomyopathy. - Strategic Updates * The company executed new strategic AI collaborations spanning discovery (with Inceptive to expand RNAi therapeutic discovery), disease identification, evidence generation, and commercial execution, building on prior AI partnerships. * Long-term strategy is anchored by three core pillars: 1) Establish global leadership in TTR amyloidosis; 2) Grow via sustainable innovation that delivers disease-modifying and curative therapies; 3) Scale with discipline to deliver durable, profitable growth, aligned with the company's 2030 vision of becoming a leading fully integrated global biopharmaceutical company focused on RNAi therapeutics.

Guidance

- Total 2026 net product revenue guidance is revised to $4.7 to $5.1 billion, down from prior guidance, driven by a downward revision to TTR revenue guidance to $4.2 to $4.5 billion (a $200 million reduction at the midpoint). The revision reflects normalization of pent-up second-line demand that was higher than initially estimated in 2025, and the revised guidance still reflects robust 75% YoY growth for TTR revenue. - Collaboration and royalty revenue guidance is revised upward to $575 to $625 million, a $150 million increase at the midpoint, driven by higher-than-expected Lectio royalties from Novartis and higher development cost reimbursement from Roche for the Zenith Phase III trial. - All other non-GAAP financial guidance for 2026 remains unchanged. - Management reaffirmed confidence in hitting the company's long-term 2030 target of 25% annual TTR revenue growth, noting that stronger-than-expected first-line growth and favorable competitive developments offset the second-line demand normalization.

Segment performance

1. TTR Franchise (Amvutra): Global net product revenue of $1.03 billion in Q2 2026, increasing 13% quarter-over-quarter (QoQ) and 89% year-over-year (YoY). Amvutra revenues exceeded $1 billion in the quarter, representing 86% of total net product revenue. US TTR revenues grew 15% QoQ and 114% YoY; ex-US TTR revenues grew 7% QoQ and 31% YoY. 2. Rare Disease Portfolio (non-TTR): Net product revenue of $142 million in Q2 2026, up 11% YoY, accounting for 12% of total net product revenue. 3. Total Global Net Product Revenue: $1.2 billion in Q2 2026, representing 74% YoY growth. Additional non-product revenue segments: Collaboration revenue of $47 million (down 23% YoY); Royalty revenue of $72 million (up 79% YoY, driven by higher Novartis Lectio sales).

Risks & headwinds

- Uncertainty remains around the Triton-CM trial outcome for Nucreceran in ATTR cardiomyopathy, even as management remains confident. While the company has options to adjust the trial protocol based on competitor data, changes could impact trial timelines or success probability. - The company faces ongoing pricing headwinds for Amvutra in ex-US markets amid new launch reimbursement negotiations. Net pricing in the US is expected to continue seeing a mid-single-digit year-over-year decline in 2026, as previously guided. - Commercial adoption depends on successful physician education around the clinical differentiation of RNAi silencers like Amvutra relative to older stabilizer therapies, particularly among lower-experience community physician prescribers. - Reimbursement policies may in some cases restrict combination use of Amvutra with background stabilizer therapies, though management notes no new changes resulting from the competitor's trial failure.

Analyst Q&A

• Q: Given the downward guidance revision, can you discuss your 12-24 month outlook and confidence in meeting long-term 25% annual growth targets? /

  A: Management acknowledges the guidance miss and takes ownership, but emphasizes that core market fundamentals are strong. 80% of ATTR-CM patients remain untreated, and strong first-line growth has fully offset the slower normalized second-line demand. Favorable competitive developments (one less expected branded competitor, delayed 2031 US generic entry for the incumbent stabilizer tefamidus) have actually increased long-term confidence, and management confirms 25% annual growth remains achievable through 2030.

• Q: After AstraZeneca's negative CardioTransform trial, are you seeing payer pushback on combination use of Amvutra with stabilizers, and can you update US net price expectations? /

  A: It is too early to see any new payer pushback: prior coverage policies remain in place, combination use restrictions were already limited to a small number of Medicare Advantage plans, and fee-for-service coverage follows Amvutra's existing label. The CardioTransform result does not change Amvutra's clinical evidence or labeling, so no major coverage changes are expected. US net price is still on track for the previously guided mid-single-digit year-over-year decline in 2026, with modest quarterly decreases continuing in H2.

• Q: What potential protocol changes could you make to Triton-CM after the competitor trial failure, and are there alternative approval paths for Nucresiran? /

  A: Management emphasizes that no changes may be needed, as the existing molecule and study design are already strong. If changes are warranted, potential adjustments fall into two main buckets: modifying enrollment criteria to enrich for subpopulations most likely to benefit, and adjusting the analytic plan for trial endpoints. While alternative approval paths (such as a non-inferiority trial against Amvutra) are technically possible, management is focused on delivering a successful outcome with the existing Triton-CM study and will not speculate on alternative paths at this time.

• Q: What is the current share of first-line new starts, how is the prescriber base split, and how will you educate community physicians on Amvutra's differentiation from stabilizers? /

  A: 80% of all new category starts are now first-line, up from a more balanced split early in the launch. Growth is already balanced across centers of excellence, academic centers, and community practices, and the company is intensifying investment to expand community adoption. Management notes that Amvutra has a unique, well-documented clinical profile with strong mortality benefits and additive effects on top of stabilizers, and that physician experience with Amvutra consistently leads to higher preference, so expanding access to experience via broader outreach will drive continued share growth.