Alnylam Pharmaceuticals, Inc. · NASDAQ:ALNY
Alnylam Pharmaceuticals — Investor Presentation (November 2022)
32 slides from Alnylam Pharmaceuticals's investor presentation, November 2022
Slide 1: Alnylam Pharmaceuticals
Nathan (USA) Diagnosed with AHP Alnylam Pharmaceuticals November 2022 1 © 2022 Alnylam Pharmaceuticals, Inc.
Slide 2: Alnylam Forward Looking Statements
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, including but not limited to expectations regarding our aspiration to become a leading biot
Slide 3: Alnylam Poised to Become a Top-Tier Biotech
Alnylam Poised to Become a Top-Tier Biotech Leader in RNAi Therapeutics • Pioneered new class of innovative medicines • 5 medicines approved in < 4 years • Robust clinical pipeline across rare and prevalent diseases • Global footprint with strong commercial capabilities • Leading IP estate with fund
Slide 4: Continuing Global Commercial Execution
Continuing Global Commercial Execution Q3 Commercial Performance Reflects Continued Steady Patient Growth TTR Ultra-Rare Disease Franchise Portfolio >2,580 >690 Patients on Therapy Patients on Therapy >2,400 >620 >2,200 >2,050 >1,875 >490 >460 >420 Q3 2021 Q4 2021 Q1 2022 Q2 2022 Q3 2022 Q3 2021 Q4
Slide 5: AMVUTTRA (vutrisiran) Update: Q3 2022
AMVUTTRA® (vutrisiran) Update: Q3 2022 Encouraging Early Launch Performance Following U.S. Approval on June 13th Doubled “New Start Form” Monthly Balanced Growth Across Broad Patient Base and Average Since Launch Account Types Encouraging Access Trends +100% PRESCRIBER BASE • Patient types: – Newly
Slide 6: Alnylam Clinical Development Pipeline
Alnylam Clinical Development Pipeline Focused in 4 Strategic Therapeutic Areas (STArs): EARLY/MID-STAGE LATE STAGE REGISTRATION/ COMMERCIAL Genetic Medicines Cardio-Metabolic Diseases (IND/CTA Filed-Phase 2) (Phase 2-Phase 3) COMMERCIAL1 RIGHTS Infectious Diseases CNS/Ocular Diseases (OLE/Phase 4/II
Slide 7: High-Yield Productivity of Alnylam RNAi Therapeutics 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 88.9 87.5 90 85.7 80 69.2 70 66.7 Percent POS 63.7 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 8: Alnylam P5x25 Goals: Performance: ≥40% revenue CAGR through YE 2025
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: Achieve sustainable non-GAAP
Slide 9: Multiple Drivers of Future Growth: TTR Franchise Leadership
Multiple Drivers of Future Growth TTR Franchise Leadership Expansion into Prevalent Diseases Engine for Sustainable Innovation Andreas (Sweden) 9 Diagnosed with hATTR amyloidosis
Slide 10: ATTR Amyloidosis
ATTR Amyloidosis Rare, Progressively Debilitating, and 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 failure
Slide 11: Alnylam TTR Franchise
Alnylam TTR Franchise Potential to Expand Value to Patients Globally for Many Years to Come Novel siRNA Conjugates^ Ocular & CNS hATTR Amyloidosis ALN-TTRsc04 ATTR Amyloidosis Patisiran TBD1 Phase 3 ATTR Amyloidosis with CM (incl. WT)‡ Stargardt Disease Biannual Dosing Vutrisiran Vutrisiran Regimen
Slide 12: Patisiran APOLLO-B Phase 3 Study Design
Patisiran Phase 3 Study Randomized, Double-Blind, Placebo-Controlled Study in ATTR Amyloidosis Patients with Cardiomyopathy N = 360 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 Secon
Slide 13: APOLLO-B Phase 3 Study Results
APOLLO-B Phase 3 Study Results Primary and First Secondary Endpoints Patisiran demonstrated statistically significant and clinically meaningful improvements in functional capacity, health status and quality of life compared to placebo at month 12 Change from Baseline in 6-MWTa Change From Baseline i
Slide 14: APOLLO-B Overall and Cardiac Safety Summary
APOLLO-B Phase 3 Study Results Overall and Cardiac Safety Summarya Patisiran Placebo At least one event, n (%) (n=181) (n=178) • Majority of AEs were mild or moderate in AEs 165 (91.2) 168 (94.4) severity SAEs 61 (33.7) 63 (35.4) Severe AEs 47 (26.0) 52 (29.2) AEs leading to treatment discontinuatio
Slide 15: Vutrisiran HELIOS-B Phase 3 Study
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 events (when Vutrisiran last patient reaches Month 30) Patient Population SC q3M 1:1 RANDOMIZATION •
Slide 16: Stargardt Disease
Stargardt Disease Promising New Opportunity for TTR-Lowering RNAi Therapeutic Description Therapeutic Hypothesis Rare, inherited, progressive form of blindness caused by accumulation of toxic vitamin A metabolites in retina leading to central vision loss Silence production of TTR in liver* High unme
Slide 17: Multiple Drivers of Future Growth: Expansion into Prevalent Diseases
Multiple Drivers of Future Growth TTR Franchise Leadership Expansion into Prevalent Diseases Engine for Sustainable Innovation 17
Slide 18: RNAi Therapeutics Profile Supports Potential Expansion to Prevalent Diseases
RNAi Therapeutics Profile Supports Potential Expansion to Prevalent Diseases • Durability • Clamped pharmacology • Safety profile evaluated in clinical trials • Improved access RARE SPECIALTY PREVALENT ONPATTRO: hATTR w/ PN1 Fitusiran Patisiran: ATTR w/ CM3 Leqvio® (inclisiran)4 ALN-HSD GIVLAARI Bel
Slide 19: Scalable Capabilities
Capabilities Support Potential Expansion to Prevalent Diseases Sophisticated, Scalable, and Global Medical and Commercial Organizations PREVALENT SPECIALTY PREVALENTALN-HSD Leqvio® (inclisiran)4 Zilebesiran (ALN-AGT) ALN-APP RARE Patisiran: ATTR w/ CM3 ALN-HBV02 (VIR-2218) ALN-XDH Vutrisiran: ATTR w
Slide 20: Reimagining Treatment of Prevalent Diseases
Reimagining Treatment of Prevalent Diseases Highly Differentiated, Infrequently Administered Therapies Against Validated Targets COMMERCIAL Hypercholesterolemia* • Biannually dosed lipid lowering therapy with effective and sustained LDL-C reduction of up to 52% • Potential to reduce ASCVD risks thro
Slide 21: RNAi Therapeutics Could Potentially Reimagine Treatment of Hypertension
RNAi Therapeutics Could Potentially Reimagine Treatment of Hypertension Need for Tonic Blood Pressure (BP) Control Potential Complications of Disease Overview Uncontrolled Hypertension Primary Hypertension1 Hypertension at high CV risk3 ~108 Million2 ~38 Million Stroke in U.S. in U.S. >71% of patien
Slide 22: Zilebesiran (ALN-AGT) Interim Phase 1 Results
Zilebesiran (ALN-AGT) Interim Phase 1 Results Results for Investigational Therapy Presented at AHA Scientific Sessions1 Dose-Dependent and Durable Reduction of Serum AGT ≥90% Sustained Reductions in SBP and DBP2 Sustained for 12 Weeks After Single Doses of zilebesiran ≥100 mg Mean 24h blood pressure
Slide 23: Early Evidence of Tonic BP Control Over Hours with Zilebesiran
Early Evidence of Tonic BP Control Over 24 Hours with Zilebesiran Zilebesiran: 24-Hour SBP at Week 6 160 DAY NIGHT Mean (+/-) SEM SBP, mmHg 150 140 130 120 110 100 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 0 1 2 3 4 5 6 7 8 Time (hour) Placebo AGT 800 mg Huang AH, Taubel J, Desai AS, et al., AHA S
Slide 24: HBV: Ongoing VIR-2218 Phase 2 Study
HBV: Global Health Problem Impacting Developed and Developing Countries Ongoing VIR-2218 Phase 2 Study Evaluating Impact of Concomitant PEG-IFNα in Chronic HBV Significant Proportion Achieve HBsAg <10 IU/mL, Including <LOQ • VIR-2218 alone or in combination with PEG- IFNα has been generally well tol
Slide 25: Multiple Drivers of Future Growth: Engine for Sustainable Innovation
Multiple Drivers of Future Growth TTR Franchise Leadership Expansion into Prevalent Diseases Engine for Sustainable Innovation 25
Slide 26: Sources of Sustainable Innovation
Sources of Sustainable Innovation Platform Innovation Extrahepatic Delivery Human Genetics GEMINI™ 12 months Novel conjugates IKARIA™ • Two-decade track record of industry • Potential for delivery to range of organs • Sourcing novel, genetically validated leadership in RNAi • C16 conjugate provides
Slide 27: GEMINI Platform: Suppress Two Targets
Potential to Potently, Durably, Safely and Conveniently Suppress Two Targets GEMINI Platform • Goal of silencing two gene transcripts using single chemical entity • Ensures uptake of both siRNAs in same cell • Potentially simplified development path vs. two entities or combination • Potential to add
Slide 28: ALN-APP: First Investigational RNAi Therapeutic for CNS
ALN-APP: First Investigational RNAi Therapeutic for CNS New Potential Approach in Alzheimer’s Disease and Cerebral Amyloid Angiopathy 100 CSF sAPPα and sAPPβ Knockdown Proprietary C16 conjugate for delivery to CNS (Single Intrathecal Dose in NHP) (% remaining relative to baseline) • IT administratio
Slide 29: Delivering Sustainable Innovation with RNAi Therapeutics
Delivering Sustainable Innovation with RNAi Therapeutics UK Our Future Literature Collaborations New Tissues Biobank Health (e.g., REGN) TRANSFORMATIVE MEDICINES Global Regulatory Development Phase 1 Phase 2 Phase 3 Submissions Candidate (e.g., NDA, MAA) 29
Slide 30: Alnylam 2022 Goals
Alnylam 2022 Goals Early Mid Late Combined Net Product Revenue Guidance $870 million – $930 million APOLLO-B Phase 3 Topline Results PATISIRAN hATTR/ATTR Amyloidosis Submit sNDA for ATTR with cardiomyopathy FDA Approval U.S. Launch VUTRISIRAN* hATTR/ATTR Amyloidosis EMA Approval Biannual Dose Regime
Slide 31: Nurturing a Culture to Ensure Future Success
Nurturing a Culture to Ensure Future Success Commitment to People Scientific Innovation Diversity, Equity, & Inclusion Social Responsibility 31
Slide 32: Challenge Accepted
To those who say “impossible, impractical, unrealistic,” we say: CHALLENGE ACCEPTED 32 © 2022 Alnylam Pharmaceuticals, Inc.
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