Alnylam Pharmaceuticals, Inc. · NASDAQ:ALNY
Alnylam Pharmaceuticals — Investor Presentation (January 2021)
39 slides from Alnylam Pharmaceuticals's investor presentation, January 2021
Slide 1: Alnylam Pharmaceuticals
Glaucienne Living with AHP (Brazil) Alnylam Pharmaceuticals January 2021 © 2021 Alnylam Pharmaceuticals, Inc. 1
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
Slide 3: Our Last 5-Year Strategy
Our Last 5-Year Strategy GOAL TARGET ACHIEVED Strategic Therapeutic Areas (STArs) 3 4 ✓ Marketed Products 3 4 ✓ Clinical Programs 10 12 ✓ 3 Late Stage Programs 4 6 ✓
Slide 4: Our New 5-Year Strategy
Our New 5-Year Strategy Patients: Over 0.5 million on Alnylam RNAi therapeutics globally Products: 6+ marketed products in rare and prevalent diseases Pipeline: Over 20 clinical programs, with 10+ in late stages and 4+ INDs per year Performance: ≥40% revenue CAGR through YE 2025 Profitability: Achie
Slide 5: RNAi Therapeutics: New Class of Innovative Medicines
RNAi Therapeutics: New Class of Innovative Medicines Clinically and Commercially Established Approach with Transformational Potential Nobel Prize-winning science Silence any gene in genome with siRNAs Potent and durable mechanism of action Product engine for sustainable innovation Multiple products
Slide 6: Transformational Medicines, Robust R&D Pipeline, Organic Product Engine
Mayah Living with PH1 (USA) TRANSFORMATIONAL ROBUST & HIGH-YIELD ORGANIC 6 MEDICINES R&D PIPELINE PRODUCT ENGINE
Slide 7: Transformational Medicines
Mayah Living with PH1 (USA) TRANSFORMATIONAL 7 MEDICINES
Slide 8: Transformational Medicines for Rare & Prevalent Diseases
RNAi Therapeutics: Transformational Medicines for Rare & Prevalent Diseases Four Global Approvals in Just Over 2 Years Leqvio® (inclisiran) Hereditary ATTR Amyloidosis Acute Hepatic Porphyria Primary Hyperoxaluria Type 1 Hypercholesterolemia with Polyneuropathy U.S. Switzerland U.S. EU EU EU Brazil
Slide 9: 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
Slide 10: ONPATTRO Launch Update: Q4 and Year-End 2020
ONPATTRO® Launch Update: Q4 and Year-End 2020 Strong Year 2 Performance with Continued Growth ~$306M ~1,350 ONPATTRO Global 2020 Patients Worldwide on Commercial Net Product Revenues (Preliminary*) ONPATTRO at YE 2020 ROW ~$90M* ~1,350 U.S. $82.5M ~47* 43.5 >1,150 $66.7M $66.5M >1,050 $55.8M 29.5 34
Slide 11: 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 Early ATTR Amyloidosis† CM (including Wild-Type)‡ Biannual Dosing Vutrisiran Vutrisiran Regimen CM (including Wild-Type)† PN &
Slide 12: 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
Slide 13: GIVLAARI Launch Update: Q4 and Year-End 2020
GIVLAARI® Launch Update: Q4 and Year-End 2020 Strong Year 1 Performance with Continued Growth ~$55M ~200 GIVLAARI Global 2020 Patients Worldwide on Commercial Net Product Revenues (Preliminary*) GIVLAARI at YE 2020 ~$22M* ROW ~5* ~200 U.S. $16.7M 4.6 ~17* >150 $11.0M 12.1 2.3 >100 8.7 $5.3M 5.3 >50
Slide 14: 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
Slide 15: Primary Hyperoxaluria Type 1
Primary Hyperoxaluria Type 1 Ultra-Rare Orphan Pediatric Disease with Significant Disease Burden 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 Car
Slide 16: The third RNAi therapeutic is now approved in the EU & U.S.
The third RNAi therapeutic is NOW APPROVED IN THE EU & U.S. 16
Slide 17: OXLUMO Market Opportunity
OXLUMO™ (lumasiran) Market Opportunity First-in-Class Target Product Profile in Ultra-Rare Orphan Disease PREVALENCE DIAGNOSIS DISEASE BURDEN COST BURDEN ~3,000 ~50% 30–65% $1M+ potentially symptomatic currently diagnosed1; mean time reach end-stage renal average cost (transplant & patients in U.S./
Slide 18: Additional Alnylam and Partner Launches Planned Over Next 12-24 Months
Additional Alnylam and Partner Launches Planned Over Next 12-24 Months Compelling Commercial Profile of Existing and Emerging Medicines 2018 2019 2020 2020 2022-2023 Leqvio® Vutrisiran Fitusiran* (inclisiran) ONPATTRO is indicated in the GIVLAARI is indicated in the OXLUMO is indicated in the Leqvio
Slide 19: Robust & High-Yield R&D Pipeline
Mayah Living with PH1 (USA) ROBUST & HIGH-YIELD 19 R&D PIPELINE
Slide 20: Alnylam Clinical Development Pipeline
Alnylam Clinical Development Pipeline Focused in 4 Strategic Therapeutic Areas (STArs): Genetic Medicines Cardio-Metabolic Diseases EARLY/MID-STAGE LATE STAGE REGISTRATION/ COMMERCIAL (IND/CTA Filed-Phase 2) (Phase 2-Phase 3) COMMERCIAL1 RIGHTS Infectious Diseases CNS/Ocular Diseases (OLE/Phase 4/II
Slide 21: High-Yield Productivity of Alnylam RNAi Platform
High-Yield Productivity of Alnylam RNAi Therapeutics Platform Comparison of Historical Industry Metrics to Alnylam Portfolio1 Probability of Success (POS) by Phase Transition 100 90 85.7 87.5 83.3 80 69.2 70 Percent POS 63.7 62.5 60 50 44.5 38.6 40 35.2 30 27.4 20 10.3 10 5.7 0 % POS, Phase 1 to 2 %
Slide 22: Vutrisiran Phase 3 Study
Vutrisiran Phase 3 Study Randomized, Open-Label Study in Hereditary ATTR Amyloidosis Patients N ~ 164 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 Impair
Slide 23: HELIOS-A Positive Topline Results
HELIOS-A Positive Topline Results Randomized, Open-Label Study in Patients with Hereditary ATTR Amyloidosis with Polyneuropathy (N=164) Positive results for all Month 9 primary and secondary efficacy endpoints, relative to APOLLO placebo Endpoint P-value Neuropathy Impairment (mNIS+7) 3.54 x 10 -12
Slide 24: Opportunity for Biannual Vutrisiran Dosing Regimen
Opportunity for Biannual Vutrisiran Dosing Regimen Plan to Further Strengthen Market Leadership • Plan to generate TTR reduction and safety data in patients receiving 50mg q6M to support sNDA to add biannual dosing regimen aligned with FDA input • Expect start of q6M dosing study in early 2021 Phase
Slide 25: RNAi Therapeutics Opportunity for ATTR Amyloidosis
RNAi Therapeutics Opportunity for ATTR Amyloidosis Potential for Broad Impact of TTR Silencing Across Disease Spectrum POLYNEUROPATHY CARDIOMYOPATHY ONPATTRO PATISIRAN PATISIRAN Primary endpoint Post hoc analyses1 IIS2 • mNIS+7 VUTRISIRAN • Reduction in mortality and • Clearance of cardiac All secon
Slide 26: ATTR Amyloidosis Franchise Phase 3 Program
ATTR Amyloidosis Franchise Phase 3 Program Randomized, Double-Blind, Placebo-Controlled Studies in ATTR Amyloidosis Patients with Cardiomyopathy patisiran vutrisiran N ~ 300 N ~ 600 hereditary & wild-type hereditary & wild-type 6-minute walk test mortality & cardiovascular events 12 months 30 months
Slide 27: Encouraging Evidence for RNAi Therapeutics in ATTR Cardiomyopathy
Encouraging Evidence for RNAi Therapeutics in ATTR Cardiomyopathy1 Results from Exploratory Endpoints in APOLLO2 and Matched Control Case Series3 • 55% Relative reduction in NT-proBNP vs. placebo2,† ~60 y.o. man with V30M mutation • 0.9mm Mean reduction in LV wall thickness vs. placebo2,‡ Mixed phen
Slide 28: RNAi Profile Supports Expansion to Prevalent Diseases
RNAi Therapeutics Profile Supports Expansion to Prevalent Diseases • Durability • Clamped pharmacology • Established safety profile • Improved access RARE SPECIALTY PREVALENT ONPATTRO-PN Fitusiran ONPATTRO-CM Leqvio® (inclisiran) ALN-HSD GIVLAARI ALN-AAT02 Vutrisiran-CM ALN-HBV02 (VIR-2218) ALN-XDH
Slide 29: RNAi Therapeutics to Reimagine Treatment of Hypertension
RNAi Therapeutics to Reimagine Treatment of Hypertension Opportunity for Tonic Blood Pressure Control Potential Complications of Uncontrolled Disease Overview Hypertension Primary Hypertension1 Hypertension at high CV risk2 ~108 Million ~38 Million Stroke in U.S. in U.S. >71% of patients have uncont
Slide 30: ALN-AGT Interim Phase 1 Results
ALN-AGT Interim Phase 1 Results Potent, Highly Durable Efficacy and Encouraging Safety Dose-Dependent AGT Lowering1 Dose-Dependent Reductions in SBP and DBP2 >95% AGT Knockdown following Single Injection >15 mmHg Systolic BP Reduction at Week 8 following Single Injection 30 5 20 10 0 Change from Bas
Slide 31: Organic Product Engine
Mayah Living with PH1 (USA) ORGANIC 31 PRODUCT ENGINE
Slide 32: 2-4 INDs per year from organic product engine
Over 25 Preclinical Programs in Four Tissues Feeding Sustainable Innovation Alnylam Alnylam/Regeneron Alnylam Alnylam/Vir • ALN-XDH • ALN-APP • ALN-TTRoc • ALN-COV • ALN-KHK • ALN-HTT • ALN-VIR2 (ACE2) • ALN-LEC • ALN-REGN-C3 Alnylam/Regeneron • ALN-VIR3 (TMPRSS2) • ALN-CC3 • ALN-REGN-C4 • ALN-REGN-
Slide 33: Alnylam Platform Expands Opportunities for Novel RNAi Therapeutics
Alnylam Platform Expands Opportunities for Novel RNAi Therapeutics Human Genetics New Tissues Novel mAb Combos + Bis-RNAi™ Reversir™ Novel Administration Target 1 Target 2 Linker BBB penetration 33
Slide 34: Guidance, Goals & Financials
Guidance, Goals & Financials 34
Slide 35: Alnylam 2021 Goals
Alnylam 2021 Goals Early Mid Late Global Commercial Execution (ATTR Amyloidosis) Complete APOLLO-B Phase 3 Enrollment Global Commercial Execution (Acute Hepatic Porphyria) Japan Approval Global Commercial Execution Brazil Approval (Primary Hyperoxaluria Type 1) ILLUMINATE-C Phase 3 Topline HELIOS-A
Slide 36: Transition to Self-Sustainable Financial Profile
Transition to Self-Sustainable Financial Profile Alnylam Entering Period of Projected Growth on Path to Profitability $2,000,000 Strong 2020 YE balance sheet of $1.9B* $1,500,000 • $2B strategic partnership with Blackstone anchors path toward self- Non-GAAP Operating Income/Loss sustainable financia
Slide 37: Financial Summary and Guidance as of November 5, 2020
Financial Summary and Guidance as of November 5, 2020 Three Months Ended Three Months Ended Full Year 2020 Guidance Financial Results ($ millions) September 30, 2020 September 30, 2019 (as of November 5, 2020) ONPATTRO Net Product Revenues $82.5 $46.1 $295 - $310 GIVLAARI Net Product Revenues $16.7
Slide 38: Building a Top-Five Biotech
Building a Top-Five Biotech Potential for Significant Transformation of Alnylam over Next 5 Years 2020 2025 Rare Rare & Prevalent Diseases Diseases Initial Multiple Indications Indications Top 5 independent, global biopharma company admired for its dedication to 4 STArs 4+ STArs patients, corporate
Slide 39: Challenge Accepted
To those who say “impossible, impractical, unrealistic,” we say: CHALLENGE ACCEPTED © 2021 Alnylam Pharmaceuticals, Inc. 39
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