Alnylam Pharmaceuticals, Inc. · NASDAQ:ALNY
Alnylam Pharmaceuticals — Investor Presentation (October 2022)
33 slides from Alnylam Pharmaceuticals's investor presentation, October 2022
Slide 1: Alnylam Pharmaceuticals
Nathan (USA) Diagnosed with AHP Alnylam Pharmaceuticals October 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 Q2 Commercial Performance Reflects Continued Steady Patient Growth >2,400 patients >420 patients >200 patients as of June 30, 2022 >2,400 as of June 30, 2022 >420 as of June 30, 2022 >200 >400 >2,200 >2,050 >350 >1,875 >160 >1,725 >300 >140 >270 >120 ~100 Q2 20
Slide 5: AMVUTTRA (vutrisiran) Update: Initial Launch Progress
AMVUTTRA® (vutrisiran) Update: Initial Launch Progress Promising Early Indicators Following U.S. Approval on June 13 PERFORMANCE HCP & PATIENT OUTREACH HEALTH SYSTEMS & PAYERS EARLY HIGHLIGHTS Encouraging early demand signal Initial promotion / education efforts Positive payer interactions • 111 Sta
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: 2022 Expected to Deliver Multiple Catalysts with Value-Creation Potential
2022 Expected to Deliver Multiple Catalysts with Value-Creation Potential Full 18-Month HELIOS-A Phase 3 Results with Vutrisiran Early 2022 Cemdisiran Phase 2 Data in IgA Nephropathy Early 2022 FDA Approval of Vutrisiran Mid-2022 APOLLO-B Phase 3 Results with Patisiran Mid-2022 ALN-HSD Phase 1 Part
Slide 9: Alnylam P5x25 Goals: Performance and Profitability
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 10: 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) 10 Diagnosed with hATTR amyloidosis
Slide 11: 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 12: 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 Vutrisiran Phase 3 ATTR Amyloidosis with CM (incl. WT)‡ Stargardt Disease Biannual Dosing Vutrisiran Vutrisiran Re
Slide 13: Patisiran APOLLO-B Phase 3 Study
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 14: 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 15: 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 16: 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 17: Stargardt Disease
Stargardt Disease Promising New Opportunity for Vutrisiran 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 unmet medical need with
Slide 18: 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 18
Slide 19: 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 20: Capabilities Support Potential Expansion to Prevalent Diseases
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 21: 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 22: RNAi Could Potentially Reimagine Treatment of Hypertension
RNAi Therapeutics Could Potentially Reimagine Treatment of Hypertension Opportunity 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
Slide 23: 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 24: 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 Losartan: 24-Hour SBP at Week 4a 160 160 DAY NIGHT DAY NIGHT Mean (+/-) SEM SBP, mmHg 150 150 140 140 130 130 120 120 110 110 100 100 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 0 1 2 3 4 5 6 7 8 9 1
Slide 25: 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 26: 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 26
Slide 27: 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 28: Potential to Suppress Two Targets: GEMINI Platform
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 S-2 S-1 + • Potent
Slide 29: 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 30: 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) 30
Slide 31: 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 hATTR/ATTR Amyloidosis VUTRISIRAN* EMA Approval Biannual Dose Regime
Slide 32: Nurturing a Culture to Ensure Future Success
Nurturing a Culture to Ensure Future Success Commitment to People Scientific Innovation Diversity, Equity, & Inclusion Social Responsibility 32
Slide 33: Challenge Accepted
To those who say “impossible, impractical, unrealistic,” we say: CHALLENGE ACCEPTED 33 © 2022 Alnylam Pharmaceuticals, Inc.
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