Alnylam Pharmaceuticals, Inc. · NASDAQ:ALNY

Alnylam Pharmaceuticals — Investor Presentation (May 2020)

38 slides from Alnylam Pharmaceuticals's investor presentation, May 2020

  1. Slide 1: Alnylam Pharmaceuticals

    Alnylam Pharmaceuticals May 2020 © 2020 Alnylam Pharmaceuticals, Inc. 1

  2. Slide 2: Forward Looking Statements & Non-GAAP Financial Measures

    Alnylam Forward Looking Statements & Non-GAAP Financial Measures 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. There are a number of important factors that could cause act

  3. Slide 3: RNAi Therapeutics: New Class of Innovative Medicines

    RNAi Therapeutics: New Class of Innovative Medicines Clinically Proven Approach with Transformational Potential Nobel Prize-winning science Silence any gene in genome Potent and durable mechanism of action Product engine for sustainable innovation Multiple products impacting patients globally 3

  4. Slide 4: The first RNAi therapeutic is approved

    The first RNAi therapeutic is APPROVED IN U.S., EU, CANADA, JAPAN, SWITZERLAND & BRAZIL 4

  5. Slide 5: ATTR Amyloidosis

    ATTR Amyloidosis Rare, Progressively Debilitating, and Often Fatal Disease Description Caused by misfolded TTR protein that accumulates as amyloid deposits in multiple GI: Diarrhea tissues including heart, nerves, and GI tract1 Nausea Vomiting CARDIAC: GU: Hereditary ATTR (hATTR) Amyloidosis Heart f

  6. Slide 6: ONPATTRO Launch Update: Q1 2020

    ONPATTRO® Launch Update: Q1 2020 Strong Performance with Significant Growth $66.7M >950 ONPATTRO Global Q1 Patients Worldwide on Commercial Net Product Revenues ONPATTRO at end of Q1 2020 ROW $66.7M Patients worldwide on commercial ONAPTTRO U.S. 29.5 >950 $55.8M 20.0 $46.1M >750 $38.2M 12.5 >600 10.

  7. Slide 7: Alnylam ATTR Amyloidosis Franchise

    Alnylam ATTR Amyloidosis Franchise Potential to Expand Value to Patients Globally for Many Years to Come Novel siRNA Conjugates^ Ocular & CNS hATTR Amyloidosis Vutrisiran C PN, Mixed, CM (including Wild-Type), Vutrisiran & Carriers† PN & Mixed† Vutrisiran PN, Mixed, & CM (including Wild-Type)† PN, M

  8. Slide 8: The second RNAi therapeutic is now approved in the U.S. & EU

    The second RNAi therapeutic is NOW APPROVED IN THE U.S. & EU 8

  9. Slide 9: Acute Hepatic Porphyria (AHP)

    Acute Hepatic Porphyria (AHP) Family of Rare Genetic Diseases with Significant Disease Burden Description Central Nervous System Causes potentially life-threatening • Confusion • Anxiety attacks and chronic manifestations Autonomic Nervous System • Severe abdominal pain • Depression • Memory loss th

  10. Slide 10: GIVLAARI (givosiran) U.S. Label

    GIVLAARI® (givosiran) U.S. Label Indication GIVLAARI is indicated for the treatment of adults with acute hepatic porphyria (AHP) Dosing & Dosing: Administration • 2.5 mg/kg via subcutaneous injection once monthly Administration: • GIVLAARI is intended for subcutaneous use only by a healthcare profes

  11. Slide 11: GIVLAARI Launch Update: Q1 2020

    GIVLAARI® Launch Update: Q1 2020 Strong Initial Demand in U.S. $5.3M >50 GIVLAARI Q1 Patients on Commercial GIVLAARI Net Product Revenues at end of Q1 2020 (U.S.) U.S. Patients on commercial GIVLAARI (U.S.) Submitted Start Forms* (since launch) >60 $5.3M 5.3 >50 13 $0.2M Q4 2019 Q1 2020 Q4 2019 Q1 2

  12. Slide 12: GIVLAARI Market Opportunity

    GIVLAARI® (givosiran) Market Opportunity Ultra-Rare Orphan Disease with Significant Disease Burden and Limited Treatment Options PREVALENCE DIAGNOSIS DISEASE BURDEN COST BURDEN ~3,000 ~20-50% 65% $400–650K patients in U.S./EU, diagnosed currently diagnosed; recurrent attack patients average annual e

  13. Slide 13: Multiple Launches Planned in Next 12-24 Months

    Multiple Launches Planned in Next 12-24 Months 2018 2019 2020 2021 Partnered programs*: 2020-2021 Lumasiran Vutrisiran Inclisiran Fitusiran ONPATTRO is indicated in the GIVLAARI is indicated in the Primary hyperoxaluria type 1 ATTR amyloidosis Hypercholesterolemia Hemophilia U.S. for the treatment o

  14. Slide 14: Commercial Products and Late Stage Clinical Development Pipeline

    Alnylam Commercial Products and Late Stage Clinical Development Pipeline Focused in 4 Strategic Therapeutic Areas (STArs): Genetic Medicines Cardio-Metabolic Diseases BREAKTHROUGH LATE STAGE REGISTRATION COMMERCIAL COMMERCIAL DESIGNATION (Phase 2-Phase 3) RIGHTS Infectious Diseases CNS/Ocular Diseas

  15. Slide 15: Patisiran Phase 3 Study

    Patisiran Phase 3 Study Randomized, Double-Blind, Placebo-Controlled Study in ATTR Amyloidosis Patients with Cardiomyopathy N ~ 300 Primary Endpoint Patient Population Patisiran • Change in 6-MWT at 12 months IV q3w† 1:1 RANDOMIZATION • ATTR amyloidosis; wild-type or 0.3 mg/kg any TTR mutation Key S

  16. Slide 16: Phase 3 Study Results: Patisiran in ATTR Cardiomyopathy

    Phase 3 Study Results Encouraging Evidence for Patisiran’s Potential in ATTR Cardiomyopathy1 ~50% Reduction in all-cause hospitalization and mortality in post-hoc analysis* • Relative reduction in NT-proBNP vs. placebo† Composite Rate of All-Cause 55% ‒ Effect noted as early as 9 months Hospitalizat

  17. Slide 17: Patisiran Treatment of hATTR Amyloidosis

    Patisiran Treatment of hATTR Amyloidosis Evidence for Potential Cardiac Amyloid Regression1 ~60 y.o. man with V30M mutation enrolled in EAP Mixed phenotype: polyneuropathy predominant Initiated patisiran (on top of diflunisal) due to disease progression Baseline 12 Months • Recent uncontrolled case

  18. Slide 18: Vutrisiran Opportunity

    Vutrisiran Opportunity Advancing Continued Innovation to Patients with ATTR Amyloidosis Mean max TTR KD of 83% after single 25 mg dose* Vutrisiran Phase 1 Study – Healthy Volunteers† DOSES -40 1.4 4 PER YEAR Mean [+/-SEM] TTR Knockdown Relative Placebo (N=20) 5mg (N=6) -20 1.2 25mg (N=6) 50mg (N=6)

  19. Slide 19: Vutrisiran Phase 3 Program

    Vutrisiran Phase 3 Program Robust Registrational Program to Evaluate Vutrisiran in Heredtiary & Wild-Type ATTR Amyloidosis Randomized, double-blind, placebo- Randomized, open-label study in controlled outcomes study in hereditary hereditary ATTR amyloidosis patients and wild-type ATTR amyloidosis pa

  20. Slide 20: Vutrisiran Phase 3 Study (HELIOS-A)

    Vutrisiran Phase 3 Study Randomized, Open-Label Study in Hereditary ATTR Amyloidosis Patients N ~ 160 Vutrisiran 3:1 RANDOMIZATION Patient Population SC q3M 25 mg • hATTR amyloidosis; 9-Month Efficacy^ 18-Month Efficacy any TTR mutation • Assessment vs. • Assessment vs. Open-Label • Neuropathy Impai

  21. Slide 21: Vutrisiran Phase 3 Study (HELIOS-B)

    Vutrisiran Phase 3 Study Randomized, Double-Blind Outcomes Study in ATTR Amyloidosis Patients with Cardiomyopathy Primary Endpoint N ~ 600 • Composite outcome of all-cause mortality and recurrent CV Vutrisiran hospitalizations (when last patient reaches Month 30) Patient Population SC q3M 1:1 RANDOM

  22. Slide 22: Primary Hyperoxaluria Type 1

    Primary Hyperoxaluria Type 1 Lumasiran Description Rare autosomal recessive disorder Retinal Oxalosis of increased oxalate synthesis resulting in kidney stones and renal failure, with subsequent oxalate accumulation in extra-renal tissues Cardiomyopathy Nephrocalcinosis Renal stones Onset generally

  23. Slide 23: Lumasiran NDA and MAA Filed

    Lumasiran NDA and MAA Filed Robust Registrational Program to Evaluate Lumasiran Across all Ages and Full PH1 Disease Spectrum Double-blind, placebo- Single arm, open-label study Single arm, open-label study controlled trial in PH1 in PH1 patients less than 6 in PH1 patients with impaired patients at

  24. Slide 24: Lumasiran Phase 3 Study

    Lumasiran Phase 3 Study Topline Results Primary Endpoint p-value Percent change from baseline in 24-hour urinary oxalate excretion, averaged across months 3 to 6 relative to placebo 1 . 6 9 x 1 0 -14 Secondary Endpoints p-value Absolute change from baseline in 24-hour urinary oxalate corrected for b

  25. Slide 25: Lumasiran Market Opportunity

    Lumasiran Market Opportunity First-in-Class Target Product Profile in Ultra-Rare Orphan Disease PREVALENCE DIAGNOSIS DISEASE BURDEN COST BURDEN ~3–5K ~50% 30–65% $1M+ patients in U.S./EU1 currently diagnosed2; mean time reach end-stage renal average cost (transplant & to diagnosis ~6 years3 disease

  26. Slide 26: Late Stage Partnered Program Opportunities

    Late Stage Partnered Program Opportunities INCLISIRAN FITUSIRAN Hypercholesterolemia Hemophilia A or B, with and without inhibitors Adults WW with high LDL-C; ASCVD Patients WW with hemophilia A or B, with 40% leading cause of death WW ~200K and without inhibitors Patients in key markets with ASCVD

  27. Slide 27: Early Stage Clinical Development and 2020 IND Pipeline

    Alnylam Early Stage Clinical Development and 2020 IND Pipeline Focused in 4 Strategic Therapeutic Areas (STArs): Genetic Medicines Cardio-Metabolic Diseases HUMAN BREAKTHROUGH 2020 IND EARLY STAGE COMMERCIAL POC1 DESIGNATION CANDIDATES (Phase 1-Phase 2) RIGHTS Infectious Diseases CNS/Ocular Diseases

  28. Slide 28: ALN-AGT for Hypertension

    ALN-AGT for Hypertension Unmet Need, Mechanism of Action, and Initial Phase 1 Topline Results Preventable Causes of Death in the U.S.1 Reduced Blood Pressure ALN-AGT Initial Phase 1 Topline Results (N=48)2 • >90% AGT knockdown Results to be presented at • >10 mmHg reduction in mean 24-h systolic blo

  29. Slide 29: COVID-19 Targeting Strategy

    COVID-19 Targeting Strategy Broad, Multifaceted RNAi Therapeutics Effort with Vir RNA TMPRSS2 ACE2 RNA Virus • SARS-CoV-2 RNA genome and viral transcripts • Selected development candidate, ALN-COV (VIR-2703), with potent and highly cross-reactive activity; plan for accelerated IND filing at or aroun

  30. Slide 30: RNAi Therapeutics for CNS and Ocular Diseases

    RNAi Therapeutics for CNS and Ocular Diseases Expand Alnylam Opportunities Beyond Liver Devastating diseases with enormous burden and unmet need • Alzheimer’s disease • Huntington’s disease • AMD, dry • Fuch’s dystrophy • Amyotrophic lateral sclerosis • Multi-system atrophy • AMD, wet • hATTR amyloi

  31. Slide 31: Guidance, Goals, & Perspective

    Guidance, Goals, & Perspective 31

  32. Slide 32: Alnylam STArs: Marketed Products and Clinical Programs

    LAlnylan. 3 STAs DEEEEL:,> 4 3 Marketed Products Sm 64 10 Clinical ProgramS =ommmm> 14 4 Late Stage Programs =m §=66

  33. Slide 33: Alnylam 2020 Goals

    Alnylam 2020 Goals 2020* *Early is Q1-Q2, Mid is Q2-Q3, and Late is Q3-Q4 Early Mid Late Global Commercial Execution Brazil Approval Additional Country Launches (ATTR Amyloidosis) APOLLO-B Enrollment EMA Approval Global Commercial Execution Additional ENVISION Results (Acute Hepatic Porphyria) Addit

  34. Slide 34: Productivity of Alnylam RNAi Therapeutic Platform

    Productivity of Alnylam RNAi Therapeutic Platform Comparison of Historical Industry Metrics to Alnylam Portfolio1 Probability of Success (POS) by Phase Transition 100 90 87.5 83.3 80.0 80 70 Percent POS 60.2 59.0 58.4 60 50 44.5 38.6 40 35.2 30 27.4 20 10.0 10 5.5 0 % POS, Phase 1 to 2 % POS, Phase

  35. Slide 35: Path to Self-Sustainability

    Path to Self-Sustainability A Top Priority for Alnylam $1,500,000 Non-GAAP Net Operating Income/Loss ($1,000s) Strong Q1 2020 balance sheet of $1.37B* • $2B strategic partnership with Blackstone anchors path toward self- $1,000,000 sustainable financial profile without need for future equity financi

  36. Slide 36: Building a Top-Tier Biotech

    Building a Top-Tier Biotech Potential for Significant Transformation of Alnylam over Next 6 Years Today 2025 Approved Approved Top 5 independent, global 2 Products 8+ Products biopharma company Late Stage Late Stage admired for its dedication to 6 Programs 10+ Programs patients, corporate culture, 4

  37. Slide 37: Financial Summary and Guidance as of May 6, 2020

    Financial Summary and Guidance as of May 6, 2020 Three Months Ended Three Months Ended Full Year 2020 Guidance Financial Results ($ millions) March 31, 2020 March 31, 2019 (as of May 6, 2020) ONPATTRO Net Product Revenues $66.7 $26.3 $270 - $300 GIVLAARI Net Product Revenues $5.3 - Net Revenue from

  38. Slide 38: Challenge Accepted

    To those who say “impossible, impractical, unrealistic,” we say: CHALLENGE ACCEPTED © 2020 Alnylam Pharmaceuticals, Inc. 38

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