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1 © 2026 Alnylam Pharmaceuticals, Inc. October 29, 2026 Third Quarter 2026 Financial Results
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2 Agenda Josh Brodsky Vice President, Investor Relations01 Welcome Yvonne Greenstreet, M.D. Chief Executive Officer02 Overview Tolga Tanguler Chief Commercialization Officer03 Commercial Highlights Pushkal Garg, M.D. Chief Research & Development Officer04 R&D and Pipeline Perspective Jeff Poulton Chief Financial Officer05 Financial Summary 06 Q&A Session
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3 Alnylam Forward-Looking Statements This presentation contains forward-looking statements. Forward looking statements include statements regarding Alnylam’s expectations, beliefs, goals, plans or prospects including, without limitation, statements regarding: the potential for continued growth of AMVUTTRA and Alnylam’s ATTR-CM franchise; the potential for Alnylam to achieve durable TTR leadership and for AMVUTTRA to be a foundational treatment and the first-line treatment of choice in ATTR-CM; the potential for Alnylam’s commercial initiatives and investments to broaden AMVUTTRA’s prescriber base, drive adoption at scale, and ultimately increase patient starts and demand for AMVUTTRA; the potential for prescriber utilization of AMVUTTRA to deepen with experience; the significant opportunity for ex-US markets to support Alnylam’s TTR global leadership ambitions; the potential for the ATTR-CM category to continue to grow and for such growth to be robust; the potential impact of any changes to the 340B Drug Pricing Program and payor utilization management policies such as step therapy requirements for AMVUTTRA or any of Alnylam’s other products, and the potential for any actions taken by Alnylam to mitigate potential risks to patient access on account of such changes; the potential success of the TRITON-PN and TRITON-CM clinical trials of nucresiran and the potential for nucresiran to strength Alnylam’s long-term TTR position; the potential for nucresiran to achieve regulatory approval for the treatment of hATTR-PN and/or ATTR-CM; the timeline for any potential launch of nucresiran in hATTR-PN and/or ATTR- CM; the potential for Alnylam to initiate a placebo-controlled, pivotal trial of brezosiran in 2027; the potential efficacy and safety of brezosiran for the treatment of Huntington’s disease; the timing of initiation, completion of enrollment, or sharing of data from, any of Alnylam’s clinical trials; the potential for any of the programs in Alnylam’s pipeline to improve human health and create value in the years ahead; Alnylam’s ability to build a more diversified, multi-franchise business; Alnylam’s ability to achieve the goals in its Alnylam 2030 strategy and to become the leading science-driven, fully integrated biopharmaceutical company and to maximize the potential of RNAi therapeutics for patients; and 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, including statements regarding where Alnylam’s actual results are expected to fall in relation to the expected range for any of these financial metrics. 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 Form10-Q or Annual Report on Form 10-K) filed with the SEC and in its other SEC filings. 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 Q3 2026 Results Summary 1 European Huntington’s Disease Network Clinical Research Congress, October 22 -24, 2026 in Krakow, Poland; 2 Pending alignment with regulatory agencies Pipeline Progress Presented Promising Initial Phase 1 Results for Brezosiran (ALN-HTT02)1 • Mean reduction of CSF HTT of 60-64% • Placebo-controlled pivotal trial to initiate in 20272 TTR Data at ESC 2026 Demonstrate Compelling Vutrisiran Profile • Consistent benefit regardless of baseline tafamidis use • Positive impact across multisystemic manifestations of ATTR-CM • Consistent treatment effect across sexes Financial Performance $4,700M to $5,100M Reiterated 2026 Total Net Product Revenue Guidance $1,292M (+52% YoY) Q3 Total Net Product Revenues TTR Leadership Q3 Total TTR Net Revenues $1,150M (+59% YoY) Upsized Enrollment Target for TRITON-CM N ~2,250
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6 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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7 Tolga Tanguler Chief Commercialization Officer Commercial Highlights
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8 Commercial Performance in Q3 2026 1 With FX impact. For growth at CER = constant exchange rate – see the Financial Summary slide for more information. $1.29B Combined Net Product Revenues +52% YoY growth1 vs. Q3’25 +10% QoQ growth1 vs. Q2’26 Q3 2026 Overall Portfolio Rare Franchise TTR Franchise
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9 ATTR-CM Launch Continues to Fuel Franchise Growth $1.15B Total TTR Global Q3 2026 Net Product Revenues Q3 2026 TTR Franchise Highlights QoQ % Growth YoY % Growth U.S. 12% 69% ROW 10% 28% Global 12% 59% $530M $642M $703M $809M $909M $155M $185M $187M $203M $222M $12M $27M Q3 2025 $12M $20M Q4 2025 $10M $10M Q1 2026 $10M $9M Q2 2026 $10M $10M Q3 2026 $724M $859M $910M $1,030M +59% +12% U.S. ONPATTRO U.S. AMVUTTRA ROW ONPATTRO ROW AMVUTTRA • U.S. 69% increase driven by strong demand growth from ATTR-CM launch offset modestly by lower net price • ROW 28% increase primarily driven by uptake in ATTR-CM sales in Japan and Germany offset by lower CM pricing in launch markets Q3’26 vs. Q3’25 (YoY) Highlights • U.S. 12% increase driven by $81M in demand growth, a $17M inventory benefit (ending inventory: Q2 19 days, Q3 21 days), and a modest increase in net price as Q3 was aided by ~$10M in beneficial one time gross-to-net adjustments • ROW 10% increase driven primarily by growth from ongoing ATTR-CM launches in Germany, Italy, and Japan, as well as the timing of orders in partner markets Q3’26 vs. Q2’26 (QoQ) Highlights +$99M U.S. TTR vs. Q2 +$20M ROW TTR vs. Q2 +$120M Global TTR vs. Q2 $1,150M
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10 Expanding AMVUTTRA Utilization & Reach in a Growing U.S. TTR Market TRx = Total prescriptions, comprised of new Rx starts + continuing patient refill Rx’s. • [+70% TTR TRx] +XX ~37% ATTR-CM Category TRx volume growth Q3’26 vs Q3’25 ~70% growth since March ’25 And yet, ~80% of ATTR-CM patients remain untreated Category Growth +XX ~24% TRx share (total prescriptions, including new starts + continuing patient refills) in ATTR (PN/CM), through Q3’26 Fueled by depth + expanding breadth of HCP prescriber base AMVUTTRA Total Rx Share in ATTR (TRx) +XX >2,000 Prescriber Expansion Balanced utilization across COE & community settings New, unique AMV prescribers added since March ’25
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11 Committed to Patient Access Options Exist to Mitigate Access Risks Resulting From Potential 340B Reimbursement Changes • Proposed rule change would reduce hospital outpatient reimbursement for Part B medicines acquired by 340B institutions • Final rule expected imminently; effective January 1, 2027, if implemented • Anticipate legal challenges CMS Proposal Potential Provider Responses • Continue traditional 340B purchasing • Shift to WAC purchasing • Utilize alternative site-of-care strategies (e.g., home care, 3rd party infusion clinics) Alnylam Approach • Options to address potential risks to patient access focused on: • Maintaining health system access via contracting • Enabling alternative sites of care
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12 Committed to Patient Access Today, patients have broad and favorable access to AMVUTTRA ~99% of covered lives have access; large majority in 1L ~90% of patients can access treatment within ~10 miles of home Most pay $0 in out-of-pocket costs
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13 Pushkal Garg, M.D. Chief Research & Development Officer R&D and Pipeline Perspective
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14 Strongly Positioned for Durable TTR Leadership AMVUTTRA HELIOS-B Data Support AMVUTTRA as the First-Line Treatment of Choice in ATTR-CM Consistency in effect across endpoints and subgroups reinforces our conviction in AMVUTTRA as a foundational treatment in ATTR-CM. NUCRESIRAN Learnings from CARDIO-TTRansform Strengthen Our Conviction in TRITON-CM TRITON-CM combines the depth of TTR knockdown, patient population and study design required to maximize the probability of success.
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15 Key Learnings from CARDIO-TTRansform More Advanced Patient Population Suboptimal Endpoint Selection Less TTR Knockdown
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16 TRITON-CM: Optimized for Success & Broad Patient Impact Nucresiran is an investigational therapeutic in development for the treatment of ATTR amyloidosis. The safety and efficacy of nucresiran have not been established or approved by the FDA, EMA or any other health authority. Enriched for patient population most likely to benefit • BNP limits specified in inclusion/exclusion criteria Event-driven outcomes study • Primary composite of all-cause mortality and recurrent cardiovascular events Enrollment expanded from N ~1,750 to ~2,250 • Ensures adequate study power under conservative estimates of outcome event rates • Expansion further enriched for patients with early disease, expected to experience greatest benefit • Largest study to-date in ATTR-CM Launch timeline intact; expected by 2030 • Ample time to amend statistical analysis plan, if needed
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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; Alnylam-owned, -led, or –co-developed PHASE 1 PHASE 2 PHASE 3 TTR Nucresiran Nucresiran CARDIOVASCULAR Zilebesiran2 Zilebesiran REVERSIR2 METABOLIC ALN-4324 (GRB14) Rapirosiran (ALN-HSD)1 ALN-PNP1 ALN-CIDEB1 ALN-ANG31 ALN-2232 (ACVR1C) ALN-6222 (INHBE) ALN-APOC31 NEUROSCIENCE Cemdisiran1 Mivelsiran Mivelsiran ALN-SOD3 Brezosiran (ALN-HTT02)4 ALN-5288 (MAPT)4 ALN-SNCA1 HEMATOLOGY Cemdisiran1 ALN-6400 (PLG) 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 Metabolic Dysfunction-Associated Steatohepatitis (MASH) Metabolic Dysfunction-Associated Steatohepatitis (MASH) Myasthenia Gravis Cerebral Amyloid Angiopathy Alzheimer’s Disease SOD1 Amyotrophic Lateral Sclerosis Huntington’s Disease Alzheimer’s Disease Paroxysmal Nocturnal Hemoglobinuria Hereditary Hemorrhagic Telangiectasia 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 Obesity & Weight Management Von Willebrand Disease
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18 Huntington’s Disease (HD) Robs Generations of Patients of Body and Mind Progressive, Fatal Monogenic Neurodegenerative Disease 1. Liu et al., J Neurol 2015; Internal analysis based on: Lanska et al., Neurology 1988; Rodrigues et al., Mov Disord Clin Pract 2017. 2. Internal analysis based on: Medina et al., Mov Disord 2022; Ibanez et al., Nat Med 2024. Average lifespan shortened to ~10–30y1 from diagnosis Mid-40s typical symptom onset, during prime working years 50% chance each child of an affected parent inherits HD >100K symptomatic patients globally2 Movement: chorea, incoordination, falls Thinking: executive dysfunction, memory loss Mood: depression, apathy, personality change, suicidality Nancy Wexler & patient PATIENT & HD RESEARCH PIONEER Woody Guthrie PATIENT
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19 One Gene, Two Potential Culprits CAG, cytosine-adenine-guanine; HD, Huntington's disease; HTT, huntingtin. 1. Tabrizi SJ, et al. Lancet Neurol. 2022;21(7):645-658. 2. Sampaio C. Parkinsonism Relat Disord. 2024;122:106049. 3. Bates GP, et al. Nat Rev Dis Primers. 2015;1:15005. 4. Handsaker, Cell 2025 https://doi.org/10.1016/j.cell .2024.11.0385. ; 5. Landles, Brain Com 2024 https://doi.org/10.1093/braincomms/fcae410; 6. Neueder, Sci Rep 2017 https://doi.org/10.1038/s41598-017-01510-z; 7. Ferguson MW, et al. J Cent Nerv Syst Dis. 2022;14:11795735221092517. HTT1a protein Full-length HTT protein HTT1a mRNA (Exon 1) HTT mRNA (Exon 1-67) mHTT accumulation One gene, two proteins The mutant gene gives rise to full-length mutant HTT (67 exons) and a shorter, toxic isoform, HTT1a (exon 1 only)² Both likely contribute to disease Full-length mutant HTT and the shorter HTT1a isoform implicated as toxicity drivers²˙⁴⁻⁶ Many approaches miss HTT1a Not all HTT-lowering strategies in development effectively address the shorter isoform¹˙⁷ Brezosiran designed to reduce all HTT isoforms Targets a conserved region in exon 1
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20 Robust, Dose-Dependent CSF mHTT Reduction Demonstrated with SMC Assay Up to 64% Mean Reduction at Month 3 and up to 80% Individual Reduction in CSF mHTT After a Single IT Dose of Brezosiran a,b Post-baseline values reported as less than the LLoQ are set to LLoQ/2, which is the case for 16 participants in figurea and 12 in table b. LLoQ = 26.5 fM. BL, baseline; CSF, cerebrospinal fluid; IT, intrathecal; LLoQ, lower limit of quantification; mHTT, mutant huntingtin; SD, standard deviation; SE, standard error; SMC, single molecule counting immunoassay. Participants with measurement below LLoQ, n (%) SMC 16 (33.3) Placebo (N=12) Brezosiran Dose 1 (N=5) Brezosiran Dose 2 (N=4) Brezosiran Dose 3 (N=9) Brezosiran Dose 4 (N=9) Brezosiran Dose 5 (N=9) mHTT reduction Placebo (N=12) Brezosiran Dose 1 (N=5) Dose 2 (N=4) Dose 3 (N=9) Dose 4 (N=9) Dose 5 (N=9) Mean maximum observed, % (SD)b 2.9 (25.5) 35.6 (18.0) 45.5 (15.7) 52.9 (22.5) 65.7 (11.8) 64.8 (10.2) Minimum individual, %b −36.8 19.0 23.5 6.7 49.3 52.0 Maximum individual, %b 60.8 63.2 59.7 79.6 80.7 77.2
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21 Encouraging Safety & Tolerability Profile CSF WBC dashed line denotes typical reference values. CSF NfL shaded placebo range indicates maximum and minimum observed ind ividual placebo values. CSF, cerebrospinal fluid; WBC, white blood cell; NfL, neurofilament light chain; SE, standard error CSF WBC CSF NfL – Fold Change Placebo range Placebo (N=12) Brezosiran Dose 1 (N=5) Brezosiran Dose 2 (N=4) Brezosiran Dose 3 (N=9) Brezosiran Dose 4 (N=9) Brezosiran Dose 5 (N=9)
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22 Advancing Brezosiran to Pivotal Trial, Pending Regulatory Alignment Phase 1 Open-Label Extension Study Continuing Illustrative only; sequencing is not to scale and no specific start dates or study durations are implied. Brezosiran is being developed by Alnylam in collaboration with Regeneron Pharmaceuticals, Inc. PLAN TO INITIATE IN 2027 Pivotal, placebo-controlled efficacy study (adults with HD) Definitive efficacy study to test whether brezosiran can slow HD progression ONGOINGONGOING Phase 1b study (adults with HD) Single ascending dose study to characterize target engagement and safety of brezosiran Phase 1b open-label extension study (adults with HD) All participants eligible; repeat dosing every 6 months Further characterizing safety of sustained HTT lowering and potential efficacy trends over time
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24 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 ASH 2026 Phase 2 Results in HHT Q4’26 Earnings ALN-4324 Type 2 Diabetes Mellitus Initiate Phase 2 Trial H1 Brezosiran Huntington’s Disease Phase 1 Data H2 ALN-2232 Obesity & Weight Management Phase 1 Data Q4’26 Earnings Additional Programs File 3-4 INDs 2026
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25 Jeff Poulton Chief Financial Officer Financial Summary
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26 Q3 2026 Financial Summary 1 Non-GAAP R&D expenses, Non-GAAP SG&A expenses, Non-GAAP operating income, 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 and loss related to convertible debt. A reconciliation of these non -GAAP financial measures to the comparable GAAP measu res, as well as additional information regarding our use of non -GAAP financial measures, are included in the Appendix to this pr esentation and in our press release dated October 29, 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 Q3 2026 perf ormance (restated using Q3 2025 exchange rates) to actual Q3 2025 reported performance. ($ in millions) Q4 2025 Q3 2026 Cash, Cash Equivalents & Marketable Securities (period end) 2,908 3,587 ($ in millions except where noted as percentages) Q3 2025 Q3 2026 Q3 2026 vs Q3 2025 (Reported) Q3 2026 vs Q3 2025 (CER2) Total Net Product Revenues $851 $1,292 52% 53% Net Revenues from Collaborations & Royalties 398 166 -58% Collaboration Revenue 352 71 -80% Royalty Revenue 46 95 105% Total Revenues 1,249 1,458 17% 17% Total Cost of Goods Sold, Collaborations & Royalties 200 362 Gross Margin on Product Revenues 77% 72% Gross Margin on Total Revenues 84% 75% Non-GAAP Combined R&D and SG&A Expenses1 573 671 17% R&D 310 376 21% SG&A 263 296 13% Non-GAAP Operating Income1 476 425 -11% Non-GAAP Operating Margin1 38% 29% Non-GAAP Net Income1 438 2,242
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27 2026 Reiterated Full Year Guidance 1 Our 2026 FY Guidance is based upon June 30, 2026 FX rates including 1 EUR = 1.14 USD and 1 USD = 162 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 $330M - $380M. Item FY 2026 Guidance Total Net Product Revenues1 $4,700 to $5,100 million • Total Rare Net Product Revenues (GIVLAARI, OXLUMO) $500 to $600 million • Total TTR Net Product Revenues (AMVUTTRA, ONPATTRO) $4,200 to $4,500 million Net Product Revenues Growth vs. 2025 at Reported FX Rates1 57% to 71% Net Product Revenues Growth vs. 2025 at constant exchange rates (i.e., operational growth)2 57% to 70% Net Revenues from Collaborations & Royalties $575 to $625 million Non-GAAP Combined R&D and SG&A Expenses3 $2,700 to $2,800 million
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28 Q3 2026 Financial Results Q&A Session
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29 Poised for Continued Growth Pipeline Momentum Progress Toward Alnylam 2030 Commercial Execution
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31 Q3 2026 Financial Results Appendix
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32 Q3 2026: Sustained Rare Franchise Performance $142M Total Rare Global Q3 2026 Net Product Revenues Q3 2026 Rare Franchise Highlights QoQ % Growth YoY % Growth GIVLAARI 0% 21% OXLUMO 1% (1%) TOTAL Rare 0% 12% • GIVLAARI YoY +21% growth highlights: – Primarily driven by increase in global patients on therapy and timing of orders in partner markets • OXLUMO YoY -1% growth highlights: – Primarily driven by increase in global patients on therapy offset by lower net price and timing of orders in partner markets $50M $56M $49M $58M $57M $23M $30M $26M $32M $32M $21M $18M $17M $19M $18M $32M $32M $34M $34M $34M Q3 2025 Q4 2025 Q1 2026 Q2 2026 Q3 2026 $126M +12% U.S. GIVLAARI ROW GIVLAARI U.S. OXLUMO ROW OXLUMO $136M $126M $142M $142M
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33 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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34 Alnylam Pharmaceuticals, Inc. Reconciliation of Product Revenue and Growth at Constant Currency Constant Currency = Constant Exchange Rate, or CER