Alnylam Pharmaceuticals, Inc. · NASDAQ:ALNY
Alnylam Pharmaceuticals — Q4 2023 Earnings Presentation
34 slides from Alnylam Pharmaceuticals's earnings presentation, Feb 15, 2024
Slide 1: Fourth Quarter and Full Year 2023 Financial Results
Fourth Quarter and Full Year 2023 Financial Results February 15, 2024 © 2024 Alnylam Pharmaceuticals, Inc. 1
Slide 2: Agenda
Agenda Welcome • Christine Lindenboom Senior Vice President, Investor Relations & Corporate Communications Overview • Yvonne Greenstreet, MBChB, MBA Chief Executive Officer Commercial Highlights • Tolga Tanguler Chief Commercial Officer Alnylam Pipeline • Pushkal Garg, M.D. Chief Medical Officer Fin
Slide 3: 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. All statements other than historical statements of fact regarding Alnylam’s expectations, b
Slide 4: Overview
Yvonne Greenstreet, MBChB, MBA Chief Executive Officer Overview 4
Slide 5: 2023 Delivered Strong Progress Across the Business
2023 Delivered Strong Progress Across the Business Driving Robust Product Growth Extending RNAi Leadership Building a Sustainable Business Landmark partnership to Human Proof of Concept for maximize global opportunity for RNAi therapeutics in CNS zilebesiran in hypertension Combined net product reve
Slide 6: Ambitious Five-Year Strategy to Drive Growth
Ambitious Five-Year Strategy to Drive Growth 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
Slide 7: Commercial Highlights
Tolga Tanguler Chief Commercial Officer Commercial Highlights 7
Slide 8: TTR Franchise Update: Q4 2023
TTR Franchise Update: Q4 2023 $254M >4,060 Total TTR Total TTR patients Global Q4 2023 worldwide at end of Net Product Revenues Q4 2023 >3,790 >4,060 Q4 TTR Franchise Highlights >3,490 Patients on Therapy >3,160 >2,975 YoY % Growth QoQ % Growth ~1,995 ~2,370 ~640 ~1,110 ~1,670 U.S. 38% 5% ROW 28% 18
Slide 9: Ultra Rare Franchise Update: Q4 2023
Ultra Rare Franchise Update: Q4 2023 $92M >1,080 Total Ultra Rare Total Ultra Rare Global Q4 2023 patients worldwide Net Product Revenues at end of Q4 2023 >1,080 Q4 Ultra Rare Franchise Highlights >1,000 >920 Patients on Therapy >850 YoY % Growth QoQ % Growth >800 ~430 ~375 ~350 ~280 ~300 GIVLAARI
Slide 10: Alnylam Pipeline
Pushkal Garg, M.D. Chief Medical Officer Alnylam Pipeline 10
Slide 11: Building an Industry-Leading TTR Franchise
Building an Industry-Leading TTR Franchise 2022 – 2024 2025+ LONGER-TERM Products ALN-TTRsc04 Hereditary ATTR amyloidosis Hereditary ATTR amyloidosis with polyneuropathy with polyneuropathy (ONPATTRO and AMVUTTRA) (ONPATTRO, AMVUTTRA, ALN-TTRsc04) Hereditary ATTR amyloidosis with polyneuropathy Here
Slide 12: Exceptional Growth Potential in ATTR-CM Market
Exceptional Growth Potential in ATTR-CM Market # of U.S. ATTR-CM Patients 200k U.S. ATTR-CM prevalence of ~150K expected Prevalence to grow ~3% annually as elderly population increases faster than overall population* 150k Diagnosed Patients 100k ~60% Estimated First approved therapy and new testing
Slide 13: Profile of Vutrisiran Expected to Support First-Line Positioning in ATTR-CM
Profile of Vutrisiran Expected to Support First-Line Positioning in ATTR-CM Tafamidis LOE Monotherapy +/- 250k Monotherapy (Q4’28) Combo therapy Cost of combo Generic tafamidis could allow for # of U.S. ATTR-CM Patients 200k is prohibitive combo therapy if data support Prevalence 150k Diagnosed Pati
Slide 14: Positioned to Deliver Outcomes Benefit in ATTR-CM
Positioned to Deliver Outcomes Benefit in ATTR-CM Supportive Data from Patisiran in APOLLO-B Design Execution from Baseline (±SEM) 6MWT, Mean Change • Powered for outcomes; • 10% overenrolled Evidence for ~2x size and ~3x length as Disease APOLLO-B • 60% monotherapy, Stabilization 40% baseline • Enr
Slide 15: Positioned to Deliver Outcomes Benefit in ATTR-CM
Positioned to Deliver Outcomes Benefit in ATTR-CM Supportive Data from Patisiran in APOLLO-B Design Execution from Baseline (±SEM) 6MWT, Mean Change • Powered for outcomes; • 10% overenrolled Evidence for Disease Key learnings heading into HELIOS-B : ~2x size and ~3x length as • 60% monotherapy, APO
Slide 16: Enhancing HELIOS-B Statistical Plan
Enhancing HELIOS-B Statistical Plan Supports Strong and Competitive Label Focused on outcomes measures in overall AND monotherapy populations; latter expected to have largest treatment effect Secondary endpoints honed to support differentiation and potential for disease stabilization Up to 3 additio
Slide 17: Updated HELIOS-B Statistical Analysis Methodology
Updated HELIOS-B Statistical Analysis Methodology Study Duration Original Updated Study Duration Study Duration • Double-blind period up to 36 months • Double-blind period up to 36 months • Three additional months of event collection for patients enrolled later in study, enhancing • Primary analysis
Slide 18: Updated HELIOS-B Statistical Analysis Methodology
Updated HELIOS-B Statistical Analysis Methodology Primary Endpoint Original Updated • Hospitalization and mortality viewed as most important outcomes; will be analyzed in: Primary Endpoint Primary Endpoint • Composite outcome of all-cause • Composite outcome of all-cause • Overall population (100%)
Slide 19: Updated HELIOS-B Statistical Analysis Methodology
Updated HELIOS-B Statistical Analysis Methodology Secondary Endpoints Original Updated Select Secondary Endpoints Secondary Endpoints • 6-MWT distance • 6-MWT distance • Kansas City Cardiomyopathy • KCCQ-OS • Secondary endpoints streamlined to clinically Questionnaire (KCCQ OS) score • All-cause mor
Slide 20: Vutrisiran Phase 3 HELIOS-B Study
Vutrisiran Phase 3 Study Randomized, Double-Blind Outcomes Study in ATTR Amyloidosis Patients with Cardiomyopathy N = 655 Primary Endpoint Vutrisiran 1:1 RANDOMIZATION Patient Population SC q3M • Composite outcome of all-cause mortality and recurrent CV • ATTR amyloidosis; events, assessed when last
Slide 21: If Approved, Vutrisiran Expected to Have Market-Leading Profile in ATTR-CM
If Approved, Vutrisiran Expected to Have Market-Leading Profile in ATTR-CM • Targeted RNAi mechanism enables rapid knockdown Unique MOA • Upstream of approved medicines, reduces pathogenic protein Rapidly growing market with high unmet patient need Potential for • Reduction in mortality and CV hospi
Slide 22: ALN-APP Achieved Rapid and Durable Reductions in Key Biomarkers
ALN-APP Achieved Rapid and Durable Reductions in Key Biomarkers Phase 1 Results* Mark First Demonstration of Gene Silencing by RNAi Therapeutics in Human Brain Rapid and Durable Reductions Marked Reductions in CSF Aβ42 in CSF sAPPβ and Aβ40 at Month 2 75 Placebo ALN-APP 25 mg ALN-APP 50 mg ALN-APP 7
Slide 23: ALN-APP Achieved Rapid and Durable Reductions in Key Biomarkers
ALN-APP Achieved Rapid and Durable Reductions in Key Biomarkers Phase 1 Results* Mark First Demonstration of Gene Silencing by RNAi Therapeutics in Human Brain Rapid and Durable Reductions Marked Reductions in CSF Aβ42 in CSF sAPPβ and Aβ40 at Month 2 75 Placebo ALN-APP 25 mg ALN-APP 50 mg ALN-APP 7
Slide 24: Recent Pipeline Progress
Recent Pipeline Progress • Positive results from KARDIA-1 Phase 2 dose-ranging study Zilebesiran • Up to 16.7 mmHg placebo-adjusted reduction of 24-hour mean systolic blood pressure at three months Hypertension • Encouraging safety and tolerability profile • Positive Phase 1 study in healthy volunte
Slide 25: Multiple Sources of Sustainable Innovation Drive Robust Pipeline
Multiple Sources of Sustainable Innovation Drive Robust Pipeline Targeting Nine Alnylam-Led INDs Across Four Tissues by End of 2025 Extrahepatic Delivery Platform Designs Human Genetics 12 months IKARIA Reversir GEMINI By End of 2025 new liver new CNS 5 INDs 2 INDs 2 new tissues with INDs 10+ includ
Slide 26: Financial Summary and Upcoming Milestones
Jeff Poulton Chief Financial Officer Financial Summary and Upcoming Milestones 26
Slide 27: Q4 and Full Year 2023 Financial Summary
Q4 and Full Year 2023 Financial Summary Q4 Reported Q4 CER FY23 Reported FY23 CER Financial Results ($ millions) Q4 2023 Q4 2022 FY 2023 FY 2022 Growth % Growth %3 Growth % Growth %3 Net Product Revenues $346 $262 32% 30% $1,241 $894 39% 39% Net Revenues from Collaborations $76 $71 $546 $135 Royalty
Slide 28: 2024 Full Year Guidance
2024 Full Year Guidance Guidance Key Assumptions Net Product Revenue1 ONPATTRO, AMVUTTRA, GIVLAARI, $1,400M to $1,500M • Uses January 31, 2024 FX rates OXLUMO Net Product Revenue Growth vs. 2023 13% to 21% • Uses January 31, 2024 FX rates at reported Fx rates1 Net Product Revenue Growth vs. 2023 at
Slide 29: Alnylam 2024 Goals
Alnylam 2024 Goals Early Mid Late Combined Net Product Revenue Guidance to be Provided L at Q4/YE 2023 Earnings HELIOS-B Topline Results L VUTRISIRAN ATTR Amyloidosis sNDA Submission L ALN-TTRsc04* ATTR Amyloidosis Initiate Phase 3 ATTR-CM Study L KARDIA-2 Phase 2 Topline Results L ZILEBESIRAN* Hype
Slide 30: Q&A Session
Q4 and Full Year 2023 Financial Results Q&A Session 30
Slide 31: Thank You!
| || Thank You! “LAlnylam
Slide 32: Appendix
Q4 and Full Year 2023 Financial Results Appendix 32
Slide 33: Reconciliation of Selected GAAP Measures to Non-GAAP Measures
Alnylam Pharmaceuticals, Inc. Reconciliation of Selected GAAP Measures to Non-GAAP Measures (In thousands) Three Months Ended Twelve Months Ended December 31, December 31, 2023 2022 2023 2022 Reconciliation of GAAP to Non-GAAP research and development: GAAP Research and development $ 272,141 $ 262,0
Slide 34: Reconciliation of Revenue and Growth at Constant Currency
Alnylam Pharmaceuticals, Inc. Reconciliation of Revenue and Growth at Constant Currency December 31, 2023 Three Months Twelve Months Ended Ended Total TTR net product revenue growth, as reported 33 % 40 % Add: Impact of foreign currency translation (2) — Total TTR net product revenue growth at const
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