Alnylam Pharmaceuticals, Inc. · NASDAQ:ALNY
Alnylam Pharmaceuticals — Investor Presentation (January 2022)
35 slides from Alnylam Pharmaceuticals's investor presentation, January 2022
Slide 1: Alnylam Pharmaceuticals
Nathan (USA) Diagnosed with AHP Alnylam Pharmaceuticals January 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 expectations regarding our aspiration to become a leading biotech company and the
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 • 4 medicines approved in < 3 years • Robust clinical pipeline across rare and prevalent diseases • Global footprint with strong commercial capabilities • Leading IP estate with fund
Slide 4: Notable Accomplishments in 2021
Notable Accomplishments in 2021 Combined net product revenues of $662 million* Completed enrollment in two key Phase 3 studies in ATTR-CM (83% growth YoY) Advanced multiple Expanded commercial presence into >30 countries 2 NDA/sNDA submissions (vutrisiran, OXLUMO®) investigational products for preva
Slide 5: Continuing Strong Global Commercial Execution
Continuing Strong Global Commercial Execution Combined Net Product Revenues ($662M) at Upper End of Guidance Range, with 83% YoY Growth* ~$475M ~$128M ~$60M 2021 revenues 2021 revenues 2021 revenues $M ~139 $M $M ~19 ROW U.S. Global ROW U.S. Global ~41 ROW U.S. Global 120.3 113.8 16.3 102.0 69.1 14.
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 90 85.7 87.5 85.7 80 69.2 70 Percent POS 63.7 64.3 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 January 21, 2022 Société Francophone du Nerf Périphérique Potential FDA Approval of Vutrisiran Early 2022 (PDUFA date April 14, 2022) Cemdisiran Phase 2 Data in IgA Nephro
Slide 9: Alnylam P5x25 Strategy Goals
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
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 Novel siRNA Conjugates^ Potential to Expand Value to Patients Globally for Many Years to Come Ocular & CNS hATTR Amyloidosis ALN-TTRsc04 ATTR Amyloidosis Vutrisiran C Patisiran Early ATTR Amyloidosis† Vutrisiran Phase 3 ATTR Amyloidosis with CM (incl. WT)‡ Stargardt Disease Bia
Slide 13: HELIOS-A 9-Month Results
HELIOS-A 9-Month Results Randomized, Open-Label Study in Patients with Hereditary ATTR Amyloidosis with Polyneuropathy (N=164) mNIS+7 LS Mean Change from Baseline Binary Analysis at Month 9 (mITT Population) 20 100 14.76 (2.00) Percent of Patients (95% CI) 90 N=67‡ Improvement in Improvement in 15 8
Slide 14: HELIOS-A 18-Month Topline Results
HELIOS-A 18-Month Topline Results Sustained Treatment Benefit with Vutrisiran Through 18 Months Positive results for all Month 18 secondary efficacy Vutrisiran results in HELIOS-A generally comparable endpoints, relative to external placebo group to patisiran results from APOLLO*, across primary and
Slide 15: Potential Opportunity for Biannual Vutrisiran Dosing Regimen
Potential Opportunity for Biannual Vutrisiran Dosing Regimen q6M Regimen in Development to Strengthen Leadership Prospects for Future • Plan to generate TTR reduction and safety data in patients receiving 50mg q6M to support potential sNDA to add biannual dosing regimen aligned with FDA input • q6M
Slide 16: TTR Franchise Phase 3 Program
TTR Franchise Phase 3 Program Randomized, Double-Blind, Placebo-Controlled Studies in ATTR Amyloidosis Patients with Cardiomyopathy patisiran vutrisiran N = 360 N = 655 hereditary & wild-type hereditary & wild-type 6-minute walk test mortality & cardiovascular events 12 months 30 months Enrollment c
Slide 17: Reasons for Confidence in Design and Ongoing Execution of APOLLO-B
Reasons for Confidence in Design and Ongoing Execution of APOLLO-B Potential to Demonstrate Favorable Impact of Patisiran vs Placebo at 12 Months, as Measured by 6MWT Rigorous Diagnostic Criteria for Expertise in Study Design and Execution Broad Patient Population Enrolled Unique and Promisi
Slide 18: Evidence for Investigational RNAi Therapeutics in ATTR Cardiomyopathy
Evidence for Investigational RNAi Therapeutics in ATTR Cardiomyopathy1 Exploratory & Post-hoc Data from APOLLO2 Investigator-Sponsored Study from National Amyloidosis Centre, UK3 Composite Rate of All-Cause Hospitalization and Mortality2,4 • 55% Relative reduction in NT-proBNP vs. placebo2,† Patient
Slide 19: 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 20: Multiple Drivers of Future Growth
Multiple Drivers of Future Growth TTR Franchise Leadership Expansion into Prevalent Diseases Engine for Sustainable Innovation 20
Slide 21: 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-PN1 Fitusiran Patisiran: ATTR-CM2 Leqvio® (inclisiran)4 ALN-HSD GIVLAARI Belcesira
Slide 22: Commercial Capabilities Support Potential Expansion to Prevalent Diseases
Commercial 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-CM2 ALN-HBV02 (VIR-2218) ALN-XDH Vutrisiran
Slide 23: 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 24: RNAi Therapeutics 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 risk2 ~108 Million ~38 Million Stroke in U.S. in U.S. >71% of
Slide 25: 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 26: 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 27: 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 28: Multiple Drivers of Future Growth
Multiple Drivers of Future Growth TTR Franchise Leadership Expansion into Prevalent Diseases Engine for Sustainable Innovation 28
Slide 29: 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 30: Potential to Potently, Durably, Safely and Conveniently 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 S-2 S-1 + • Potent
Slide 31: 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 32: 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) 32
Slide 33: Alnylam 2022 Goals
Alnylam 2022 Goals Early Mid Late Combined Net Product Revenue Guidance to be Provided at Q4’21 Earnings APOLLO-B Phase 3 Topline Results PATISIRAN hATTR/ATTR Amyloidosis File sNDA for ATTR-CM FDA Approval (4/14/22 PDUFA) U.S. Launch hATTR/ATTR Amyloidosis VUTRISIRAN* EMA Approval Biannual Dose Regi
Slide 34: Nurturing a Culture to Ensure Future Success
Nurturing a Culture to Ensure Future Success Commitment to People Scientific Innovation Diversity, Equity, & Inclusion Social Responsibility 34
Slide 35: Challenge Accepted
To those who say “impossible, impractical, unrealistic,” we say: CHALLENGE ACCEPTED 35 © 2022 Alnylam Pharmaceuticals, Inc.
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