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1 © 2026 Alnylam Pharmaceuticals, Inc. February 12, 2026 Fourth Quarter and Full Year 2025 Financial Results
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2 Agenda Welcome • Christine Akinc Chief Corporate Communications Officer Overview • Yvonne Greenstreet, M.D. Chief Executive Officer Commercial Highlights • Tolga Tanguler Chief Commercial Officer Pipeline • Pushkal Garg, M.D. Chief Research & Development Officer Financial Summary • Jeff Poulton Chief Financial Officer Q&A Session
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3 Alnylam Forward-Looking Statements This presentation contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. All statements other than historical statements of fact regarding Alnylam’s expectations, beliefs, goals, plans or prospects including, without limitation, statements regarding Alnylam’s ability to achieve the goals in its “Alnylam 2030” strategy, including to achieve durable ATTR leadership, long-term sustainable innovation and exceptional financial results; Alnylam’s ability to deliver continued durable, long-term growth and to sustain profitability going forward; the potential for the siRELIS platform to be a best-in-class enzymatic ligation-based RNAi manufacturing platform and to greatly expand capacity and bring RNAi therapeutics to more patients around the world while reducing the cost of goods; Alnylam’s ability to launch AMVUTTRA for ATTR-CM in additional international markets during 2026, to compete effectively in those markets and to build global momentum; the size and future growth of the patient populations with hATTR-PN and ATTR-CM and the potential for broader engagement in those categories and other efforts to expand awareness, diagnosis and treatment, and to benefit patients; the potential success of the launch of AMVUTTRA in ATTR-CM; the success of Alnylam’s patient access efforts for AMVUTTRA and the potential for Alnylam to achieve broader patient access in 2026 as compared to 2025; the number of patients who will be enrolled in Alnylam’s clinical trials; the timing of commencement of, or of the completion of enrollment in, any of Alnylam’s clinical trials; the potential for any of Alnylam’s product candidates to successfully complete clinical development and to receive regulatory approval and launch commercially, and the timing of any such commercial launches; the potential efficacy, treatment effect and product profiles of any of Alnylam’s products and product candidates; the size of the market opportunities of the indications for which Alnylam’s product or product candidates would receive regulatory approval; Alnylam’s ability to achieve its pipeline goals for 2026; Alnylam’s projected commercial and financial performance, including the expected range for 2026 of TTR net product revenues, Rare net product revenues, total net product revenues, net revenues from collaborations and royalties, and non-GAAP R&D and SG&A expenses; and Alnylam’s expectations with respect to TTR revenue growth in Q1 2026 should be considered forward-looking statements. Actual results and future plans may differ materially from those indicated by these forward-looking statements as a result of various important risks, uncertainties and other factors, including, without limitation, risks and uncertainties relating to: Alnylam’s ability to successfully execute on its “Alnylam 2030” strategy; Alnylam’s ability to successfully launch, market and sell Alnylam’s approved products globally, including AMVUTTRA; Alnylam’s ability to discover and develop novel drug candidates and delivery approaches and successfully demonstrate the efficacy and safety of its product candidates; the pre-clinical and clinical results for Alnylam’s product candidates; actions or advice of regulatory agencies and Alnylam’s ability to obtain and maintain regulatory approval for its product candidates, as well as favorable pricing and reimbursement; delays, interruptions or failures in the manufacture and supply of Alnylam’s marketed products or its product candidates; obtaining, maintaining and protecting intellectual property; Alnylam’s ability to manage its growth and operating expenses through disciplined investment in operations; Alnylam’s ability to maintain strategic business collaborations; Alnylam’s dependence on third parties for the development and commercialization of certain products; the outcome of litigation and government investigations; the risk of future litigation and government investigations; and unexpected expenditures; as well as those risks and uncertainties more fully discussed in the “Risk Factors” filed with Alnylam’s most recent periodic report (Quarterly Report on Form 10-Q or Annual Report on Form 10-K) filed with the SEC and in its other SEC filings. In addition, any forward-looking statements represent Alnylam’s views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam explicitly disclaims any obligation, except to the extent required by law, to update any forward- looking statements. This presentation references non-GAAP financial measures. These measures are not in accordance with, or an alternative to, GAAP, and may be different from non-GAAP financial measures used by other companies. Percentage changes in revenue growth at Constant Exchange Rates, or CER, is a non-GAAP financial measure which is presented excluding the impact of changes in foreign currency exchange rates for investors to understand the underlying business performance. CER represents growth calculated as if the exchange rates had remained unchanged from those used during the prior fiscal year.
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4 Yvonne Greenstreet, M.D. Chief Executive Officer Overview
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5 Alnylam: A Unique Profile in the Biotech Industry Established, Sustainable Innovation Engine and Commercial Excellence to Drive Durable Growth Leadership in RNAi, with a Proven, Organic Product Engine High-Yielding Pipeline with >25 Active Clinical Programs 6 Medicines Collectively Generating Multi-Billion-Dollar Revenues
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6 2025: A Transformational Year for Alnylam Landmark Approval, Commercial Excellence Drove Outstanding Financial Performance Advanced Innovative RNAi Pipeline and Platform Capabilities Global launch of AMVUTTRA for ATTR-CM Initiated 3 Phase 3 Studies Combined net product revenues: $2,987 million (+81% YoY) Expanded clinical pipeline with 4 proprietary CTAs and 5 CTAs filed by partners Developed and launched siRELIS enzymatic ligation-based RNAi manufacturing platform 6 approved products ~500k patients >25 clinical programs ~50% revenue CAGR GAAP Profitability
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7 Alnylam 2030 Accelerating Innovation. Scaling Impact. Scale with Discipline & Agility DRIVE SUSTAINED, PROFITABLE GROWTH • Achieve 25%+ total revenue CAGR through YE 2030 • Deliver ~30% non-GAAP operating margin Achieve Global TTR Leadership BUILD A DURABLE TTR FRANCHISE • Lead TTR market in revenue by 2030 and cumulatively across 5-year period • Launch best-in-class, next-gen silencer, nucresiran, in PN by 2028 and CM by 2030 Grow Through Sustainable Innovation DELIVER THERAPIES THAT PREVENT, HALT, OR REVERSE DISEASE • Deliver 2+ new transformative medicines beyond TTR with blockbuster potential • Expand to 10 tissue types and > 40 clinical programs • Invest ~30% of revenues in non-GAAP R&D, including select external innovation
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8 Tolga Tanguler Chief Commercial Officer Commercial Highlights
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9 Continued Commercial Execution in Q4 2025 1 With FX impact. For growth at CER = constant exchange rate – see the Financial Summary slide for more information. $995M Combined Net Product Revenues +121% YoY growth1 vs. Q4’24 +17% QoQ growth1 vs. Q3’25 Q4 2025 Overall Portfolio $2,987M Combined Net Product Revenues +81% YoY growth1 vs. FY’24 Full Year 2025 Overall Portfolio Rare Franchise TTR Franchise
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10 Q4 2025: Sustained Rare Franchise Performance 1 CER = Constant exchange rate, which is a non-GAAP financial measure that represents growth calculated as if exchange rates had remained unchanged from those used during 2024 – see the Financial Summary slide for more information. $45M $44M $55M $50M $56M $20M $23M $26M $23M $30M$19M $14M $16M $21M $18M$25M $28M $31M $32M $32M Q4 2024 Q1 2025 Q2 2025 Q3 2025 Q4 2025 Revenues ($M) U.S. GIVLAARI ROW GIVLAARI U.S. OXLUMO ROW OXLUMO $136M Total Rare Global Q4 2025 Net Product Revenues QoQ % Growth YoY % Growth GIVLAARI 17% 34% OXLUMO -6% 14% TOTAL Rare 8% 26% • GIVLAARI YoY +34% growth highlights: – ~17% YoY increase in global patients on therapy – Additional growth contribution from U.S. gross-to-net favorability and timing of orders in partner markets • OXLUMO YoY +14% growth highlights: – ~19% YoY increase in global patients on therapy – Offset primarily by gross-to-net unfavorability in international markets • Modest FX tailwind +3% (YoY CER1 growth = 23%) Q4 2025 Rare Franchise Highlights $108M $109M $128M $127M $136M +26%
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11 Continued AMVUTTRA ATTR-CM Launch Momentum 1 CER = Constant exchange rate, which is a non-GAAP financial measure that represents growth calculated as if exchange rates had remained unchanged from those used during 2024 – see the Financial Summary slide for more information. $20M $16M $22M $12M $12M $183M $198M $361M $530M $642M $36M $34M $30M $27M $20M $103M $112M $131M $155M $185M Q4 2024 Q1 2025 Q2 2025 Q3 2025 Q4 2025 Revenues ($M) U.S. ONPATTRO U.S. AMVUTTRA ROW ONPATTRO ROW AMVUTTRA $858M Total TTR Global Q4 2025 Net Product Revenues Q4 2025 TTR Franchise Highlights QoQ % Growth YoY % Growth U.S. 20% 222% ROW 13% 47% Global 18% 151% • U.S. Q4’25 vs. Q3’25 (QoQ) +20% growth highlights: – Continued demand growth (+24%) driven by ATTR-CM launch – Partially offset by unfavorable inventory channel impact and increase in gross-to-net deductions • U.S. Q4’25 vs. Q4’24 (YoY) +222% growth highlights: – ~250% demand growth driven primarily by ATTR-CM launch – Partially offset by increase in gross-to-net deductions, in line with our expectations of a mid-single digit decrease in net price YoY • ROW YoY +47% growth primarily driven by continued ATTR-PN patient growth and uptake in ATTR-CM sales in Japan • Modest FX tailwind +2% (YoY CER1 growth = 149%) $343M $359M $544M $724M $858M +151% +$111M U.S. vs. Q3 +$23M ROW vs. Q3 +$134M Global vs. Q3
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12 Building Leadership in Large, Growing ATTR-CM Market Select U.S. analogs are 2nd+ to market with differentiated mechanism of action, specialty/rare, Buy & Bill, or part of direct competitive set. Select Japan analogs are successful launches in the Japanese market across rare, specialty, and prevalent indi cations or direct competitive set. 1 Internal estimate based on U.S. + EU5 + Japan. 2 Internal Estimates of commercial volume based on claims data. 3 Evaluate Pharma. 4 ALNY collaboration finance reporting. 5 VYNDA and BEYONTTRA revenues are calculated estimates based on IQVIA data. Significant Unmet Need Exceptional Early Launch Momentum U.S. Japan 0 1 2 3 4 WINREVAIR 3 ATTRUBY 3 LEQVIO 4 OCREVUS 3 SAPHNELO 3 VYVGART 3 VYNDA family3 Quarterly Revenue Quarters Post Launch AMVUTTRA In ATTR-CM Quarters Post Launch VYVGART 3 OPSUMIT 3 OPDIVO 3 0 1 2 3 4 AMVUTTRA In ATTR-CM GALAFOLD 3 Quarterly Revenue VYNDA family in CM 5 DUPIXENT 3 HEMLIBRA 3 BEYONTTRA 5 ~80% ATTR-CM patients undiagnosed globally1 >300K patients globally1 40%+ Average Annual Category Volume Growth Since 20192
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13 Establishing Preference Across Lines of Therapy Market share of new treatment starts (NRx), quarterly average. All market share numbers are estimates only. Internal estimat es based on claims data available through September 2025. Patient indication cohorts identified using latest diagnoses across me dical and pharmacy claims. Maintaining Broad Access and Patient AffordabilityATTR-CM: Building Leadership in Growing Category • First-line access (i.e., no step edit required) for large majority of U.S. covered lives • $0 in out-of-pocket costs for majority of patients • ~90% of patients can receive AMVUTTRA treatment within ~10 miles of where they live Competitive in New Starts Building First-Line Preference ALL new starts (both first- and second-line) Clear Second-Line Leadership Q1’25 Q2’25 Q3’25 Q1’25 Q2’25 Q3’25 Q1’25 Q2’25 Q3’25 AMVUTTRA VYNDAMAX ATTRUBY Market Share (NRx, Quarter Average) Market Share (NRx, Quarter Average) Market Share (NRx, Quarter Average) 41% 37% 22% 51% 27% 21% 6% 69% 25%
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Kelly, treated with Amvuttra J O I N U S F O R A W E B I N A R TO M A R K One Year Since FDA Approval of AMVUTTRA in ATTR-CM Highlighting progress in delivering for ATTR-CM patients and the long-term growth and durability of the Company’s flagship TTR franchise. SAVE THE DATE Tuesday, March 24TH 9:30 am ET Webcast Registration information forthcoming
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15 Pushkal Garg, M.D. Chief Research & Development Officer Pipeline
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16 Advanced Pipeline & Platform Capabilities in 2025 Initiated 3 Phase 3 Studies Expanded Clinical Pipeline Launched New RNAi Manufacturing Platform • ALN-2232 • ALN-5288 • ALN-4285 • ALN-4915 siRELIS Fully dedicated, proprietary siRNA enzymatic ligation manufacturing facility 4 Alnylam Proprietary CTAs 5 Partner-led CTAs
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17 Industry Leading Pipeline of RNAi Therapeutics 1 Out-licensed with milestones and/or royalties; 2 Partnered, Alnylam-led development with U.S. profit split and milestones/royalties ex -U.S.; 3 Partner-led with profit split; 4 Partnered, Alnylam-led with profit split PHASE 1 PHASE 2 PHASE 3 TTR Nucresiran Nucresiran CARDIOVASCULAR Zilebesiran2 Zilebesiran + REVERSIR2 METABOLIC Rapirosiran (ALN-HSD)1 ALN-ANG31 ALN-4324 (GRB14) ALN-2232 (ACVR1C) ALN-PNP3 ALN-APOC31 ALN-CIDEB1 NEUROSCIENCE Cemdisiran1 Mivelsiran Mivelsiran ALN-HTT024 ALN-5288 (MAPT)4 ALN-SOD3 ALN-SNCA3 HEMATOLOGY Cemdisiran1 ALN-6400 (PLG) AG-236 (ALN-TMP)1 ALN-CFB1 OTHER Cemdisiran1 Elebsiran1 ALN-BCAT ALN-4285 ALN-4915 ALN-F12021 ATTR Amyloidosis with Cardiomyopathy hATTR Amyloidosis with Polyneuropathy Hypertension Hypertension Metabolic Dysfunction-Associated Steatohepatitis (MASH) Dyslipidemia Type 2 Diabetes Mellitus Non-Alcoholic Fatty Liver Disease (NAFLD) MASH Myasthenia Gravis Cerebral Amyloid Angiopathy Alzheimer’s Disease SOD1 Amyotrophic Lateral Sclerosis Huntington’s Disease Alzheimer’s Disease Paroxysmal Nocturnal Hemoglobinuria Bleeding Disorders Polycythemia Vera Paroxysmal Nocturnal Hemoglobinuria Hepatitis D Virus Infection Diabetic Kidney Disease Hepatocellular Carcinoma Geographic Atrophy Healthy Volunteers Obesity & Weight Management Parkinson’s Disease Healthy Volunteers Healthy Volunteers
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18 Next Wave of Transformative Medicines Investigational Therapies with Multi-Billion-Dollar Potential MIVELSIRAN Cerebral Amyloid Angiopathy and Alzheimer’s Disease ZILEBESIRAN Hypertension ALN-HTT02 Huntington’s Disease ALN-6400 Bleeding Disorders ALN-4324 Type 2 Diabetes Mellitus ALN-2232 Obesity & Weight Management CARDIOVASCULAR + METABOLIC NEUROSCIENCE HEMATOLOGY
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19 2026 Pipeline Goals to Drive Our Next Phase of Growth Products mentioned above are not approved for any indication and conclusions regarding the safety or effectiveness of these d rugs have not been established. Nucresiran ATTR Amyloidosis Advance TRITON-CM Phase 3 Trial Ongoing Advance TRITON-PN Phase 3 Trial Ongoing Zilebesiran Hypertension Advance ZENITH Phase 3 Trial Ongoing Mivelsiran Cerebral Amyloid Angiopathy Complete Enrollment of cAPPricorn-1 Phase 2 Trial H1 Alzheimer’s Disease Initiate Phase 2 Trial H1 ALN-6400 Bleeding Disorders Initiate Phase 2 Trial in Second Bleeding Disorder H1 Phase 1 Data in Healthy Volunteers H2 Phase 2 Results in HHT H2 ALN-4324 Type 2 Diabetes Mellitus Initiate Phase 2 Trial H1 ALN-HTT02 Huntington’s Disease Phase 1 Data H2 ALN-2232 Obesity & Weight Management Phase 1 Data H2 Additional Programs File 3-4 INDs 2026
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20 Jeff Poulton Chief Financial Officer Financial Summary
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21 Q4 and Full Year 2025 Financial Summary 1 Non-GAAP R&D expenses, Non-GAAP SG&A expenses, Non-GAAP operating income / (loss), Non-GAAP Operating Margin, and Non-GAAP Net Income are non-GAAP financial measures that exclude from the corresponding GAAP measures costs related to stock -based compensation expense, loss related to convertible debt, and realized and unrealized gains or losses on marketable equity secu rities. A reconciliation of these non-GAAP financial measures to the comparable GAAP measures, as well as additional information re garding our use of non-GAAP financial measures, are included in the Appendix to this presentation and in our press release dated February 12, 2026, which is accessible in the Investors section of our website at www.alnylam.com. 2 CER growth rates represent growth at Constant Exchange Rates, a non-GAAP financial measure determined by comparing Q4 2025 performance (restated using Q4 2024 exchange rates) to actual Q4 2024 reported performance. 3 CER growth rates represent growth at Constant Exchange Rates, a non -GAAP financial measure determined by comparing 2025 performance (restated using 2024 exchange rates) to actual 2024 reported performance. ($ in millions except where noted as percentages) Q4 2024 Q4 2025 Q4 2025 vs Q4 2024 (Reported) Q4 2025 vs Q4 2024 (CER2) FY 2024 FY 2025 FY25 vs FY24 (Reported) FY25 vs FY24 (CER3) Total Net Product Revenues $451 $995 121% 119% $1,646 $2,987 81% 80% Net Revenues from Collaborations & Royalties 142 102 (28)% 602 727 21% Collaboration Revenue 107 41 (62)% 510 553 8% Royalty Revenue 35 61 73% 92 174 90% Total Revenues 593 1,097 85% 83% 2,248 3,714 65% 64% Total Cost of Goods Sold, Collaborations & Royalties 103 268 323 682 Gross Margin on Product Revenues 77% 73% 81% 77% Gross Margin on Total Revenues 83% 76% 86% 82% Non-GAAP Combined R&D and SG&A Expenses1 504 626 24% 1,830 2,182 19% R&D 260 341 31% 998 1,166 17% SG&A 244 285 17% 831 1,016 22% Non-GAAP Operating Income / (Loss) 1 (14) 203 95 850 Non-GAAP Operating Margin1 (2%) 19% 4% 23% Non-GAAP Net Income / (Loss)1 8 170 (3) 684 ($ in millions) Q4 2024 Q4 2025 Cash, Cash Equivalents & Marketable Securities (period end) 2,695 2,908
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22 2026 Full Year Guidance 1 Our 2026 FY Guidance is based upon December 31, 2025 FX rates including 1 EUR = 1.17 USD and 1 USD = 157 JPY 2 CER = constant exchange rate, representing growth calculated as if exchange rates had remained unchanged from those used in 2 025. CER is a non-GAAP financial measure 3 2026 Non-GAAP Combined R&D and SG&A Expenses guidance is a non-GAAP financial measure that excludes from the corresponding GAAP measure stock-based compensation expense estimated at $300M - $400M. Item FY 2026 Guidance Key Assumptions Total Net Product Revenues1 $4,900 to $5,300 million • Total Rare Net Product Revenues (GIVLAARI, OXLUMO) $500 to $600 million • Total TTR Net Product Revenues (AMVUTTRA, ONPATTRO) $4,400 to $4,700 million • U.S. TTR category growth consistent with recent run rate • U.S. AMVUTTRA mid-single digit net price decrease • International markets TTR $ growth similar to 2025 Net Product Revenues Growth vs. 2025 at Reported FX Rates1 64% to 77% • Uses December 31, 2025 FX rates Net Product Revenues Growth vs. 2025 at constant exchange rates (i.e., operational growth)2 64% to 77% • Uses 2025 actual FX rates Net Revenues from Collaborations & Royalties $400 to $500 million Non-GAAP Combined R&D and SG&A Expenses3 $2,700 to $2,800 million
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23 Q1 2026 TTR Revenue Phasing Expectations Item FY 2026 Guidance Key Assumptions Total Net Product Revenues1 $4,900 to $5,300 million • Total Rare Net Product Revenues (GIVLAARI, OXLUMO) $500 to $600 million • Total TTR Net Product Revenues (AMVUTTRA, ONPATTRO) $4,400 to $4,700 million • U.S. TTR category growth consistent with recent run rate • U.S. AMVUTTRA mid-single digit net price decrease • International markets TTR $ growth similar to 2025 Net Product Revenues Growth vs. 2025 at Reported FX Rates1 64% to 77% • Uses December 31, 2025 FX rates Net Product Revenues Growth vs. 2025 at constant exchange rates (i.e., operational growth)2 64% to 77% • Uses 2025 actual FX rates Net Revenues from Collaborations & Royalties $400 to $500 million Non-GAAP Combined R&D and SG&A Expenses3 $2,700 to $2,800 million $12M $12M $530M $642M $27M $20M$155M $185M Q3 2025 Q4 2025 Revenues ($M) U.S. ONPATTRO U.S. AMVUTTRA ROW ONPATTRO ROW AMVUTTRA • International Q1’26 TTR revenue expected to decrease ~ $25M from Q4 primarily due to updated CM launch pricing in Germany • Expect positive quarterly international TTR revenue growth beyond Q1 • U.S. Q1’26 TTR quarterly revenue growth expected to be more modest than $111M of Q4 growth primarily due to the following phasing effects: – Fewer product shipping weeks in Q1 vs Q4 – Insurance reauthorizations • Expect higher quarterly U.S. TTR revenue growth beyond Q1 $724M $858M +$134M Global vs. Q3 +$23M ROW vs. Q3 +$111M U.S. vs. Q3
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24 2026 Full Year Guidance 1 Our 2026 FY Guidance is based upon December 31, 2025 FX rates including 1 EUR = 1.17 USD and 1 USD = 157 JPY 2 CER = constant exchange rate, representing growth calculated as if exchange rates had remained unchanged from those used in 2 025. CER is a non-GAAP financial measure 3 2026 Non-GAAP Combined R&D and SG&A Expenses guidance is a non-GAAP financial measure that excludes from the corresponding GAAP measure stock-based compensation expense estimated at $300M - $400M. Item FY 2026 Guidance Key Assumptions Total Net Product Revenues1 $4,900 to $5,300 million • Total Rare Net Product Revenues (GIVLAARI, OXLUMO) $500 to $600 million • Total TTR Net Product Revenues (AMVUTTRA, ONPATTRO) $4,400 to $4,700 million • U.S. TTR category growth consistent with recent run rate • U.S. AMVUTTRA mid-single digit net price decrease • International markets TTR $ growth similar to 2025 Net Product Revenues Growth vs. 2025 at Reported FX Rates1 64% to 77% • Uses December 31, 2025 FX rates Net Product Revenues Growth vs. 2025 at constant exchange rates (i.e., operational growth)2 64% to 77% • Uses 2025 actual FX rates Net Revenues from Collaborations & Royalties $400 to $500 million Non-GAAP Combined R&D and SG&A Expenses3 $2,700 to $2,800 million
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25 Q4 and Full Year 2025 Financial Results Q&A Session
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27 Q4 and Full Year 2025 Financial Results Appendix
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28 Alnylam Pharmaceuticals, Inc. Reconciliation of Selected GAAP Measures to Non-GAAP Measures (In thousands) Please note that the figures presented above may not sum exactly due to rounding
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29 Alnylam Pharmaceuticals, Inc. Reconciliation of Product Revenue and Growth at Constant Currency Constant Currency = Constant Exchange Rate, or CER