Alnylam Pharmaceuticals, Inc.

Overview

• Global commercial-stage biopharmaceutical company focused on RNA interference (RNAi) therapeutics.
• Pioneered RNAi-based medicines that silence disease-relevant mRNA.
• Two core delivery approaches:
  • GalNAc conjugates for liver-targeted delivery (subcutaneous administration; potential dosing intervals: monthly, quarterly, bi-annual).
  • Lipid nanoparticle (LNP) delivery for liver targeting (e.g., ONPATTRO).
• Developing extrahepatic delivery for brain/CNS and ocular targets using a hexadecyl (C16) moiety and other technologies.
• Alnylam 2030 strategy (launched early 2026) aims to expand to 10 tissue types and more than 40 clinical programs by 2030.
• Maintains a late-stage pipeline and multiple collaborations to access development, regulatory and commercialization capabilities, and milestone-based financing.

Products and commercial scope

Six marketed RNAi medicines, with additional products commercialized by collaborators:

• AMVUTTRA (vutrisiran)

  • Target: transthyretin (TTR) for ATTR amyloidosis with polyneuropathy.
  • Approvals: U.S. for hATTR polyneuropathy; EU/UK for adult polyneuropathy; Japan for TTR-type familial amyloidosis with polyneuropathy.
  • sNDA approved in 2025 for TTR cardiomyopathy in the U.S.; regulatory activity ongoing in EU/UK/Japan and other territories.

• ONPATTRO (patisiran)

  • Target: TTR for hATTR polyneuropathy.
  • Approvals: U.S. and EU for hATTR polyneuropathy; expanded approvals in Brazil (2025) for ATTR with cardiomyopathy; available in other territories.

• GIVLAARI (givosiran)

  • Target: acute hepatic porphyria (AHP).
  • Approvals: U.S. for adults; EU for adults and adolescents (12+); approvals in other countries; additional regulatory filings pending.

• OXLUMO (lumasiran)

  • Target: primary hyperoxaluria type 1 (PH1).
  • Approvals: U.S. for PH1 (all ages including pediatric); EU/UK and other countries; regulatory filings ongoing in additional territories.

• Leqvio (inclisiran) — developed and commercialized by Novartis

  • Target: PCSK9 for LDL-C lowering.
  • Approvals: EU and FDA for certain indications; approvals in China and Japan; registered in over 100 countries and marketed in 89 countries by end-2025.

• Qfitlia (fitusiran) — developed and commercialized by Sanofi under license

  • Target: antithrombin (AT) for hemophilia with or without inhibitors.
  • Approvals: FDA (March 2025) for routine prophylaxis in adults and patients aged 12+; NMPA approval in China (December 2025).
  • Sanofi holds global rights under collaboration/licensing terms.

• Context: Leqvio and Qfitlia had approvals or label expansions in 2025. Alnylam continues to pursue regulatory activity and launches across multiple territories.

Development and pipeline

• Six approved products plus multiple late- and early-stage RNAi programs.
• Next-generation and extrahepatic delivery programs include:
  • nucresiran (IKARIA platform) for ATTR amyloidosis
    • Phase 3: TRITON-PN (polyneuropathy) started Sept 2025; TRITON-CM (cardiomyopathy) started June 2025.
  • zilebesiran (ALN-AGT01) for hypertension
    • Roche collaboration for co-development/commercialization.
    • Phase 3 cardiovascular outcomes trial (ZENITH) initiated in 2025.
  • mivelsiran (ALN-APP) for CNS/brain targets (CAA/AD)
    • Regeneron collaboration; Phase 1/2 updates in 2025; Phase 2 planned in 2026.
  • ALN-HTT02 for Huntington’s disease (Regeneron collaboration)
    • Phase 1b initiated Oct 2025; data expected H2 2026.
  • ALN-6400 targeting bleeding disorders (PLG)
    • Early Phase 2 in HHT underway; additional Phase 2 planned in 2026.
• Early-stage and preclinical activity: plans to file three or more INDs/CTAs in 2026 and continued focus on extrahepatic delivery and CNS programs via the Regeneron collaboration.

Collaboration and licensing strategy

• Roche Collaboration and License Agreement (July 2023) — zilebesiran

  • Structure: Worldwide collaboration; Roche holds co-exclusive U.S. development and commercialization rights and exclusive rights outside the U.S.; non-exclusive manufacturing rights outside the U.S.
  • Financials: $310 million upfront; a $65 million development milestone (April 2024) for first patient in KARDIA-3; $300 million development milestone (Sept 2025) for first patient in ZENITH; potential contingent milestones up to $2.15 billion.
  • Economics: Development costs generally shared (40% Alnylam / 60% Roche for most development activities to regulatory approval); U.S. cost-sharing 50/50; Roche bears commercialization costs outside the U.S.; royalties and profit-sharing apply per agreement.

• Other collaborations and license arrangements

  • Regeneron: collaborations covering CNS programs (e.g., mivelsiran, ALN-HTT02) and joint development/commercialization terms.
  • Novartis: Leqvio (inclisiran) development and commercialization collaboration and prior licensing arrangements related to PCSK9 programs.
  • Vir Biotechnology: elebsiran for HBV/HDV; amended 2025 agreement assigns primary development/commercialization responsibility to Vir while Alnylam retains royalties and milestone entitlements.
  • Cemdisiran: Regeneron-led development and commercialization, including monotherapy and combination approaches with pozelimab; milestones/updates occurred in 2025.

Capital structure and liquidity (as of December 31, 2025)

• Convertible senior notes

  • 2028 Notes: aggregate principal $661.3 million; 0.00% interest; maturity Sept 15, 2028; convertible at holders’ option beginning June 15, 2028; settlement may be cash, stock, or a combination.
  • Capped calls were entered in connection with the issuance (initial cap price ~ $837.61 per share).
  • Note repurchase activity: Sept 2025 privately negotiated repurchases of approximately $637.8 million aggregate principal amount of 2027 Notes; Dec 2025 repurchases of approximately $34.4 million aggregate principal amount; outstanding 2027 Notes remaining approximately $362.8 million after these repurchases.

• Revolving credit facility

  • $500.0 million revolving line of credit with a $150.0 million letter of credit sublimit.
  • Maturity date: Sept 30, 2030 (subject to customary conditions and potential incremental facilities).
  • As of Dec 31, 2025: no borrowings under the facility; $17.5 million of letters of credit outstanding.
  • Covenants and fees: SOFR-based borrowings carry margins of 1.50%–2.50% depending on leverage; unused commitment fee of 0.20%–0.35%; obligations guaranteed by certain domestic subsidiaries and secured by assets.

Alnylam 2030 strategy and financial goals

• Revenue and profitability targets
  • Target: 25%+ total revenue CAGR through year-end 2030.
  • Target: approximately 30% non-GAAP operating margin.
• Growth and portfolio strategy
  • Launch next-generation therapies (e.g., nucresiran) and extend leadership in TTR to drive sustained growth.
  • Generate two or more new transformative medicines beyond TTR with blockbuster potential.
  • Expand to 10 tissue types and over 40 clinical programs.
  • Reinvest roughly 30% of revenues in non-GAAP R&D to sustain organic innovation while maintaining disciplined scaling and agile operations.

Summary

Alnylam is a leading RNAi therapeutics company with a diversified marketed portfolio, multiple late-stage programs, and active collaborations to support development and commercialization. The company focuses on liver-targeted therapies while advancing extrahepatic delivery for CNS and ocular targets, and it pursues strategic growth under the Alnylam 2030 plan. Financing is managed through convertible debt, a revolving credit facility, capped-call structures, and selective note repurchases.