Alnylam Pharmaceuticals, Inc. · NASDAQ:ALNY
Alnylam Pharmaceuticals — Technical Presentation (April 2021)
30 slides from Alnylam Pharmaceuticals's technical presentation, Apr 19, 2021
Slide 1: HELIOS-A Phase 3 Study of Vutrisiran: Full 9-Month Results
HELIOS-A Phase 3 Study of Vutrisiran Full 9-Month Results April 19, 2021 © 2021 Alnylam Pharmaceuticals, Inc. 1
Slide 2: Agenda
Agenda Welcome • Christine Lindenboom Senior Vice President, Investor Relations & Corporate Communications Introduction • John Maraganore, Ph.D. Chief Executive Officer Disease Overview & HELIOS-A 9-Month Results • Akshay Vaishnaw, M.D., Ph.D. President of R&D Commercial Preparedness & Next Steps •
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, including expectations regarding our ability to achieve our “Alnylam P5x25” strategy, the p
Slide 4: Introduction
John Maraganore, Ph.D. Chief Executive Officer Introduction 4
Slide 5: 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 Patisiran Vutrisiran C Early ATTR Amyloidosis† CM (including Wild-Type)‡ Biannual Dosing Vutrisiran Vutrisiran Regimen CM (including Wild-Ty
Slide 6: Productivity of Alnylam RNAi Therapeutic Platform
Productivity of Alnylam RNAi Therapeutic Platform Comparison of Historical Industry Metrics to Alnylam Portfolio 1 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 % POS, Phase
Slide 7: Additional Launches Planned Over Next 12-24 Months
Additional Launches Planned Over Next 12-24 Months 2018 2019 2020 2020-2021 2022-2023 Leqvio® Vutrisiran Fitusiran5 (inclisiran) ONPATTRO is indicated in the GIVLAARI is indicated in the OXLUMO is indicated in the Leqvio is approved in the EU for ATTR amyloidosis Hemophilia U.S. for the treatment of
Slide 8: 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 9: Disease Overview & HELIOS-A 9-Month Results
Akshay Vaishnaw, M.D., Ph.D. President of R&D Disease Overview & HELIOS-A 9-Month Results 9
Slide 10: 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 11: RNAi Therapeutic Hypothesis in ATTR Amyloidosis
RNAi Therapeutic Hypothesis in ATTR Amyloidosis Silencing TTR Gene Expression Can Potentially Address Underlying Cause of Disease Production of variant and wild-type TTR in liver* Reduce circulating TTR Prevent or clear PATISIRAN / VUTRISIRAN tissue amyloid deposits siRNA sequences selected to silen
Slide 12: Alnylam's TTR Amyloidosis Franchise
Alnylam’s TTR Amyloidosis Franchise Approved Treatment Option and Investigational Programs Vutrisiran ONPATTRO® (patisiran) is an Approved RNAi Therapeutic Vutrisiran is an Investigational RNAi Therapeutic for for Treatment of Polyneuropathy of hATTR Amyloidosis* Potential Treatment of ATTR Amyloido
Slide 13: Vutrisiran Phase 3 Study Design
Vutrisiran Phase 3 Study Randomized, Open-Label Study in Hereditary ATTR Amyloidosis Patients with Polyneuropathy N=122 9-Month Efficacy Assessment Patient Population Vutrisiran N=164 Vutrisiran vs APOLLO Placebo 25 mg 3:1 RANDOMIZATION • 18–85 years old SC Q3M Primary Endpoint • ATTRv • Change from
Slide 14: Baseline Demographic and Disease Characteristics
Baseline Demographic and Disease Characteristics APOLLO HELIOS-A Placebo Vutrisiran Patisiran Characteristic N=77 N=122 (N=42) Age (years), median (range) 63 (34, 80) 60 (26, 85) 60 (31, 81) Males, n (%) 58 (75) 79 (65) 27 (64) TTR genotype, n (%) V30M 40 (52) 54 (44) 20 (48) Non-V30M 37 (48) 68 (56
Slide 15: Rapid and Sustained Reduction in Serum TTR Levels
Rapid and Sustained Reduction in Serum TTR Levels with Vutrisiran Similar to Patisiran in HELIOS-A • Vutrisiran achieved a mean steady-state* serum TTR reduction from baseline of 83% (SD: 14%) Percent Change from Baseline in Serum TTR Levels 0 Vutrisiran (HELIOS-A) (N=122) Mean (±SE) % Change from B
Slide 16: Significant Improvement in Neuropathy Impairment with Vutrisiran
Significant Improvement in Neuropathy Impairment with Vutrisiran • Vutrisiran achieved statistically significant improvement in mNIS+7 at 9 months, compared with external placebo group – Improvements across all pre-specified patient subgroups* and components of mNIS+7 (data not shown) 20 mNIS+7 LS M
Slide 17: Significant Improvement in Quality of Life and Gait Speed
Significant Improvement in Quality of Life and Gait Speed with Vutrisiran • Vutrisiran achieved statistically significant improvement in Norfolk QOL-DN and gait speed measured by 10-MWT at 9 months, compared with external placebo group – Improvements across all pre-specified patient subgroups* and d
Slide 18: Evidence of Reversal of Polyneuropathy Disease Manifestations
Evidence of Reversal of Polyneuropathy Disease Manifestations Majority of Patients Showed Improvement in Neuropathy Impairment and Quality of Life, Relative to Baseline* Binary Analysis at Month 9 100 (mITT Population) 90 Improvement in Improvement in 80 mNIS+7 Norfolk QoL-DN* Percent of Patients (9
Slide 19: HELIOS-A and APOLLO Month 9 Efficacy Results
HELIOS-A and APOLLO Month 9 Efficacy Results Post Hoc Cross-Study Comparison HELIOS-A APOLLO Vutrisiran Patisiran (N=122) (N=148) LS mean change Vutrisiran-Placebo LS mean change Patisiran-Placebo from baseline LS mean difference from baseline LS mean difference Endpoint (95% CI) (95% CI) (95% CI) (
Slide 20: Improvement in NT-proBNP with Vutrisiran
Improvement in NT-proBNP with Vutrisiran vs External Placebo Group Exploratory Endpoint Change from Baseline in NT-proBNP Change from Baseline in NT-proBNP (mITT Population)* (Cardiac Subpopulation)† 2 2 1.59 1.60 N=67‡ Adjusted Geometric Fold Change N=32‡ Adjusted Geometric Fold Change 1.5 1.5 Plac
Slide 21: HELIOS-A Safety Summary
HELIOS-A Safety Summary* Acceptable Safety Profile of Vutrisiran The majority of AEs were mild or moderate in severity • No drug-related discontinuations or deaths APOLLO† HELIOS-A • Two study discontinuations (1.6%) due to AEs in the Placebo Vutrisiran Patisiran vutrisiran arm by Month 9, both due
Slide 22: HELIOS-A 18-Month Data to Further Assess Vutrisiran Impact
HELIOS-A 18-Month Data to Further Assess Vutrisiran Impact 18-Month Results Expected Late 2021 Additional Secondary Endpoints • Extend mNIS+7, Norfolk QOL, and 10-MWT dataset beyond 9 months with longer follow-up • Assess new secondary endpoints: mBMI, R-ODS, serum TTR reduction Exploratory Endpoint
Slide 23: HELIOS-A Month 9 Data Summary
HELIOS-A Month 9 Data Summary • HELIOS-A is a phase 3, global, open-label study of vutrisiran 25 mg SC Q3M in patients with hATTR amyloidosis with polyneuropathy • Vutrisiran met primary and both secondary endpoints at 9 months – Statistically significant improvements in neuropathy impairment (mNIS+
Slide 24: Commercial Preparedness & Next Steps
Yvonne Greenstreet, MBChB, MBA President and Chief Operating Officer Commercial Preparedness & Next Steps 24
Slide 25: Vutrisiran Planned Next Steps
Vutrisiran Planned Next Steps File NDA Initiate q6M Data Generation Early 2021 HELIOS-A Topline 18-Month Results Late 2021 U.S. Launch Early 2022 25
Slide 26: hATTR Amyloidosis Market Opportunity
hATTR Amyloidosis Market Opportunity Estimated Disease Prevalence*† ~ 50,000 patients worldwide NEUROLOGIC PHENOTYPE CARDIAC PHENOTYPE† > 50% have cardiomyopathy > 50% have neuropathy PN & MIXED† 20K to 30K worldwide ~ 10K diagnosed‡ 10K to 15K in U.S. < 3K diagnosed 5K to 10K in EU ~ 2K diagnosed *
Slide 27: Key Drivers of Potential Market Expansion with Vutrisiran
Key Drivers of Potential Market Expansion with Vutrisiran* SIGNIFICANT EFFICACY Reversed PN manifestations of disease Building on ONPATTRO foundation, in majority of HELIOS-A patients vutrisiran has potential to become treatment of choice in hATTR amyloidosis with polyneuropathy PATIENT CHOICE Addre
Slide 28: Pictures of our patients
Pictures of our patients (different from last year) 28
Slide 29: Q&A Session
HELIOS-A 9-Month Results Q&A Session 29
Slide 30: Challenge Accepted
To those who say “impossible, impractical, unrealistic,” we say: CHALLENGE ACCEPTED © 2021 Alnylam Pharmaceuticals, Inc. 30
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