Alnylam Pharmaceuticals, Inc. · NASDAQ:ALNY
Alnylam Pharmaceuticals — Investor Day (August 2026)
27 slides from Alnylam Pharmaceuticals's investor day presentation, Aug 30, 2026
Slide 1: Power of RNAi for ATTR-CM
Power of RNAi for ATTR-CM August 30, 2026 © 2026 Alnylam Pharmaceuticals, Inc. 1
Slide 2: Agenda
Agenda Yvonne Greenstreet, M.D. 01 Leadership in TTR Chief Executive Officer Pushkal Garg, M.D. 02 TRITON-CM: Designed for Success Chief R&D Officer 03 Q&A Session 2
Slide 3: Alnylam Forward-Looking Statements
Alnylam Forward-Looking Statements This presentation contains forward-looking statements. Forward looking statements include statements regarding Alnylam’s expectations, beliefs, goals, plans or prospects including, without limitation, statements regarding: Alnylam’s ability to achieve durable TTR l
Slide 4: Leadership in TTR
Leadership in TTR Yvonne Greenstreet, M.D. Chief Executive Officer 4
Slide 5: Strongly Positioned for Durable TTR Leadership
Strongly Positioned for Durable TTR Leadership AM V U T T R A N U C R E S I R AN HELIOS-B Data Support AMVUTTRA as the Learnings from CARDIO-TTRansform First-Line Treatment of Choice in ATTR-CM Strengthen Our Conviction in TRITON-CM Consistency in effect across endpoints and subgroups TRITON-CM comb
Slide 6: AMVUTTRA's Differentiated Clinical Profile Supports its Role as a Foundational, First-Line Therapy in ATTR-CM
AMVUTTRA’s Differentiated Clinical Profile Supports its Role as a Foundational, First-Line Therapy in ATTR-CM tafamidis acoramidis eplontersen Approved for the treatment of ATTR-CM in adults in the U.S. ✓ ✓ ✓ Approved for the treatment of hATTR-PN in adults in the U.S. ✓ ✓ Consistency in treatment e
Slide 7: Strong U.S. Fundamentals to Drive Future Growth of AMVUTTRA
Strong U.S. Fundamentals to Drive Future Growth of AMVUTTRA Emerging HCP Robust Continued Preference with Category Growth Broad Access Experience ~80% >1,700 ~99% ATTR-CM patients remain untreated New AMVUTTRA prescribers Overall coverage since ATTR-CM launch ~15K+ >50% >90% New to treatment ATTR-CM
Slide 8: Progressing Toward TTR Leadership
Progressing Toward TTR Leadership On the Path to Realizing Alnylam 2030 Ambitions Quarterly Sales by Product 2,000 Post AMVUTTRA CM Launch $1,762 1,800 $1,688 $1,615 $1,602 $1,591 1,600 $1,545 $1,486 1,400 1,200 $ Millions $1,030 1,000 $910 $858 800 $724 600 $544 $359 400 $343 $271 $210 $163 200 $12
Slide 9: 2H26 Readouts Unlocking the Next Wave of Transformative, RNAi-Powered Medicines
2H26 Readouts Unlocking the Next Wave of Transformative, RNAi-Powered Medicines ALN-HTT02 ALN-6400 ALN-2232 Huntington’s Disease Bleeding Disorders Obesity & Weight Management Ph 1 Data in Healthy Volunteers Phase 1 Data Phase 1 Data Ph 2 HHT Results EHDN October 23 Krakow, Poland 9
Slide 10: Alnylam 2030
Alnylam 2030 Accelerating Innovation. Scaling Impact. Achieve Global TTR Leadership BUILD A DURABLE TTR FRANCHISE • Lead TTR market in revenue by 2030 and cumulatively across 5-year period • Launch best-in-class, next-gen silencer, nucresiran, in PN by 2028 and CM by 2030 Grow Through Sustainable In
Slide 11: TRITON-CM: Designed for Success
TRITON-CM: Designed for Success Pushkal Garg, M.D. Chief Research & Development Officer 11
Slide 12: Overview
Overview • Data from a variety of amyloidotic diseases – AL, AA and hATTR-PN – all demonstrate that deep lowering of the pathogenic protein is essential to improving patient outcomes • Similarly, outcomes in these diseases further improve if therapies to reduce protein production are initiated early
Slide 13: AMVUTTRA: Powerful Efficacy from HELIOS-B Supports First-Line Use
AMVUTTRA: Powerful Efficacy from HELIOS-B Supports First-Line Use Time-to-First CV Event or ACM1 Time to ACM1 Large reductions in all-cause mortality and cardiovascular events Benefits greatest when initiated early in disease Early Patients Realize Greatest Benefit2 Consistent Effect Across Backgrou
Slide 14: TRITON-CM: Optimized for Success & Broad Patient Impact
TRITON-CM: Optimized for Success & Broad Patient Impact Targeting Launch by 2030 • Randomized, double-blind, event-driven outcomes study of nucresiran versus placebo • N ~1,750 • Includes patients on monotherapy and background stabilizer • Primary endpoint of all-cause mortality and recurrent CV eve
Slide 15: Key Cardio-TTRansform Questions Going Into ESC
Key Cardio-TTRansform Questions Going Into ESC Patient characteristics TTR knockdown disease severity across subgroups; background meds depth and time to achieve; variability Safety & tolerability Study execution adherence to study drug; competing risks completeness of follow-up Outcomes impact on e
Slide 16: What Have We Learned at ESC?
What Have We Learned at ESC? Potential Explanations for CARDIO-TTRansform Failure LESS TTR KNOCKDOWN MORE ADVANCED POPULATION ENDPOINT SELECTION Baseline CARDIO- characteristic HELIOS-B TTRansform Eplontersen1 Vutrisiran2 △ NYHA class III 17% 9% NAC stage 3 9% 5% NT-proBNP, 2,025 1,920 median pg/mL
Slide 17: Continued High Confidence in TRITON-CM Based on Data & Experience
Continued High Confidence in TRITON-CM Based on Data & Experience Our Molecule Our Study Our Track Record >15 years in TTR drug RNAi ~1,750 patients development Deep patient-level >95% TTR knockdown2 Event driven insights from prior studies Meticulous study execution 2 prior studies showing Enriched
Slide 18: Recent Datasets Suggest Advantages of RNAi Silencing
Recent Datasets Suggest Advantages of RNAi Silencing Target & Molecule Mechanism Dosing Regimen Target KD Key Trial Result AGT SBP ASO development shifted to Zilebesiran1 a follow-on asset, currently in RNAi 300 mg Q6M -93% @M6 -14.5 mmHg @M6 (monotherapy) development for a narrower, IONIS-AGT-LRX2
Slide 19: RNAi Benefit on Top of Stabilizers Supported by Strong Clinical Data
RNAi Benefit on Top of Stabilizers Supported by Strong Clinical Data ATTR Cardiomyopathy All-Cause Mortality in Patients on Background Stabilizer HELIOS-B (N=259)1 HR=0.59 (0.32, 1.08) Up to 42-month follow-up APOLLO-B (N=91)2 HR=0.56 (0.22, 1.44) 24-month follow-up 0.25 0.5 1 2 Favors drug Favors p
Slide 20: HELIOS-B Demonstrated Additive Benefit of Vutrisiran on Top of Stabilizer Therapy
HELIOS-B Demonstrated Additive Benefit of Vutrisiran on Top of Stabilizer Therapy Using CARDIO-TTRansform Primary Endpoint CARDIO-TTRansform1 HELIOS-B2 Composite of Cardiovascular Death and Recurrent Cardiovascular Events Mean Cumulative Cardiovascular Mortality and Cardiovascular Events by up to We
Slide 21: RNAi Drives Deep, Consistent Knockdown of TTR
RNAi Drives Deep, Consistent Knockdown of TTR Vutrisiran and Eplontersen Values Derived from hATTR-PN Studies Median TTR KD (%) Estimated Percent Above or Below Threshold1 100 100 99% 95% 91% 90 90 82% 80 84% 80 70 70 67% 60 60 50 50 40 40 33% 30 30 20 20 18% 10 10 1% 0 0 Eplontersen Vutrisiran Nucr
Slide 22: HELIOS-B Demonstrated Silencing Early Drives Greatest Benefit, Irrespective of Background Stabilizer Use
HELIOS-B Demonstrated Silencing Early Drives Greatest Benefit, Irrespective of Background Stabilizer Use Primary endpoint: ACM and recurrent CV events NEJM 2024 22
Slide 23: Modeling Relationship Between TTR and Outcomes in ATTR-CM Using HELIOS-B Data
Modeling Relationship Between TTR and Outcomes in ATTR-CM Using HELIOS-B Data Generate Large Develop TTR Identify Key Virtual Patient Validate Sample Patients Efficacy Model Covariates Pool Modeling from the Pool to describe association e.g., demographics, reflecting real-world by comparing model- t
Slide 24: Model Illustrates Deeper TTR Knockdown Associated with Better Outcomes in ATTR-CM
Model Illustrates Deeper TTR Knockdown Associated with Better Outcomes in ATTR-CM Modeling Time to ACM or First CV Event Model-Predicted Relationship Between Steady State TTR KD (Median) TTR KD and Hazard Ratio in HELIOS-B Population Eplontersen Vutrisiran On background stabilizer CARDIO- Nucresiran
Slide 25: Nucresiran Designed for Success in TRITON-CM
Nucresiran Designed for Success in TRITON-CM Deep TTR knockdown, early treatment and endpoint selection are critical to demonstrating outcomes benefits of TTR silencing in ATTR-CM, and point to potential reasons for CARDIO- TTRansform failure TRITON-CM optimized to demonstrate outcomes benefit • Bui
Slide 26: Q&A Session
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Slide 27: Silence disease, & Amplify life
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