Alnylam Pharmaceuticals, Inc. · NASDAQ:ALNY
Alnylam Pharmaceuticals — Investor Day (March 2026)
47 slides from Alnylam Pharmaceuticals's investor day presentation, Mar 24, 2026
Slide 1: Establishing TTR Leadership
Establishing TTR Leadership Progress in First Year Following Launch March 24, 2026
Slide 2: AMVUTTRA approved in U.S. for ATTR-CM
amvuttra Y (vutrisiran) ste March 20, 2025 Approved in U.S. for the treatment of the cardiomyopathy of wild-type or hereditary ATTR amyloidosis (ATTR-CM) WAlnylam 11 ibd tt 1f fll ie ee ee Sn a a
Slide 3: The Future of ATTR Leadership
The Future of ATTR Leadership Accelerate Advance Invest in AMVUTTRA nucresiran Cutting-Edge Uptake Capabilities Scaling global presence and market Raising the bar for clinical efficacy Investing in early diagnosis, penetration. and experience.* coordinated care, and long-term outcomes. *Assumes posi
Slide 4: Execution is Translating into Results
Execution is Translating into Results Over 100% Proven Strong 2026 Revenue execution Outlook Growth TTR franchise revenues more than Delivered two consecutive guidance Guiding to 83% growth at the mid- doubled year-over-year in 2025. raises in 2025. point.
Slide 5: Today's Panel
Today’s Panel John P. Kennedy Tolga Tanguler Mark Soued Senior Vice President, TTR Senior Vice President, Franchise Commercialization Lead Chief Commercial Officer Head of U.S. & TTR Lead Sameer Bansilal, Christine Akinc MD, MS, FACC Chief Corporate Vice President, TTR Disease Area Lead Communicatio
Slide 6: Agenda
Agenda The Opportunity The AMVUTTRA Value Proposition Strengthening Leadership Competing in silencer class Anticipating stabilizer genericization Unlocking Category Growth
Slide 7: 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 8: Driving Broad Impact in First Year of Launch
Driving Broad Impact in First Year of Launch Exceptional Early Launch Momentum >12K ATTR Patients on ALNY Treatments Globally As of March 1, 2026 U.S. Japan AMVUTTRA In ATTR-CM 3 OCREVUS 1 VYNDA3 ~1,600 Quarterly Revenue family in CM Quarterly Revenue AMVUTTRA Unique U.S. Prescribers In ATTR -CM WIN
Slide 9: We Have Built a Foundation for Durable Growth
We Have Built a Foundation for Durable Growth Preference Patient Access Provider & Utilization & Affordability Network Established 1L leadership among ~90% have first-line access, ~90% of patients in the HCPs who have tried AMVUTTRA majority pay $0 OOP US can receive AMVUTTRA within ~10 miles of hom
Slide 10: Early Launch Momentum and Strong Foundation
Early Launch Momentum and Strong Foundation; Accelerating the Next Phase of Launch Average Share of New Starts Across Enablers First Three Quarters of Launch Experience Drives Preference ~35% Utilization Drives Depth new-to-brand share despite entering as Most requested ATTR-CM brand the 3rd ATTR-CM
Slide 11: AMVUTTRA Experience Reinforces Physician Confidence & Adoption
AMVUTTRA Experience Reinforces Physician Confidence & Adoption Physician Perceptions Prior AMVUTTRA Experience to AMVUTTRA Experience Drives Preference Prior authorization 85% of prior authorizations approved on first challenges submission Concerns about ~90% 1L access; Most pay $0 buy & bill ~90% o
Slide 12: ATTR-CM Category is Large, Underserved and Growing
ATTR-CM Category is Large, Underserved and Growing Significant Unmet Need Robust & Sustained Category Growth Accelerating Since Competitor Launches 77% Growth3 ~200K U.S. patients 1 Dec‘24 – Dec’25 80% 56% Growth3 Before Competition Jan’23-Nov’24 ATTR-CM patients untreated in the U.S.2 Dec’25 Jan’23
Slide 13: Agenda: The Opportunity
Agenda The Opportunity Mark Soued Senior Vice President, Head of U.S. & TTR Lead
Slide 14: ATTR-CM Category is Large, Underserved and Growing
ATTR-CM Category is Large, Underserved and Growing Significant Unmet Need Nearly 200K U.S. patients >500K Globally 80% Untreated Patients Source: ATTR-CM, based on Alnylam modeling data
Slide 15: Category Expansion Fuels Sustained Opportunity Across U.S. Patient Segments
Category Expansion Fuels Sustained Opportunity Across U.S. Patient Segments (First Line + Switch/Add) 80% Untreated Patients1 160K Not Actively Treated New to Treatment Stabilizer Progressors2 15K+ ~15K New to Treatment Treatment Progressors Patients Annually (50% of actively treating patients on co
Slide 16: Increased Competition & New Guidelines Expected to Accelerate Category Growth
Increased Competition & New Treatment Guidelines Expected to Accelerate Category Growth Over Time 70% Diagnosis Rate Potential Growth by 2030+ Analogues reach ~70% over time1 (e.g., MS, PAH, AFib) 2019 2030+ 1. ClearView Analysis
Slide 17: Significant Opportunity Ahead
Significant Opportunity Ahead ~200K Diagnosis Multiple U.S. patients and treatment pathways rates to sustained accelerating growth More than 80% of ATTR-CM patients Growing awareness, improved First-line and switch / add-on remain untreated diagnosis, and expanded treatment patients options are driv
Slide 18: Agenda: The AMVUTTRA Value Proposition
Agenda The Opportunity The AMVUTTRA Value Proposition Sameer Bansilal, MD, MS, FACC Vice President, TTR Disease Area Lead
Slide 19: Our ambition for ATTR-CM patients
Our ambition is that ATTR-CM patients live longer better lives and adhere to treatment and ensure that patients
Slide 20: What Matters to Clinicians
What Matters to Clinicians Most Important ATTR-CM Physicians Rate AMVUTTRA Product Attributes to HCPs1 Highly on These Attributes2 85% 84% Demonstrated efficacy rate AMVUTTRA highly for in reducing mortality reducing mortality Demonstrated efficacy in 100% 86% rate AMVUTTRA highly for reducing CV-re
Slide 21: Vutrisiran Demonstrated Profound Impact on Survival
Vutrisiran Demonstrated Profound Impact on Survival Increasing Mortality Benefit Over Time Relative reduction in mortality 29% Double-Blind 34% Open Label 39% Open Label Extension Extension 36mo1 42mo1 48mo2 1. Fontana M et al. N Engl J Med. 2025;392:33–44. 2. Garcia-Pavia, P. ESC Congress 2025. htt
Slide 22: Vutrisiran Nearly Halved Extra-Cardiac Adverse Effects
Vutrisiran Nearly Halved Extra-Cardiac Adverse Effects Overall Population 42% mean reduction in cumulative GI events1 1. Urey MA, et al. Oral presentation at the Heart Failure Society of America (HFSA) Annual Meeting, September 26-29, 2025, Minneapolis, MN.
Slide 23: Vutrisiran Drove Amyloid Regression and Cardiac Improvement
Vutrisiran Drove Amyloid Regression and Cardiac Structure And Function Improvement 220 LV Mass1* 22% 210 LV Mass (g) 200 190 180 170 0 12 24 36 Months 110 LV Stroke Volume1* amyloid regression LV Stroke Volume (ml) 100 90 in patients treated with vutrisiran 80 vs. 63% progressed on placebo1 70 60 0
Slide 24: Adhere to Treatment: Alnylam RNAi Treatment Persistence
Hi Adhere to Treatment | Alnylam RNAi Treatment Persistence; 2x Advantage vs. Once Daily Oral Stabilizer hATTR-PN Patients Peripheral Nerve Society 2025: Conciecao, I, et al.
Slide 25: Continuing to Add to a Robust Body of Evidence
Continuing to Add to a Robust Body of Evidence DemonsTTRate Observational Study Capture Range of Patient- & HCP-Function 2,000 Real-World Evidence and Outcomes patients Enabling Comparative & Combination Treatment Evidence Generation
Slide 26: Our ambition: live longer, live better, adhere to treatment
Our ambition is that ATTR-CM patients live longer and better lives and ensure that patients adhere to treatment Live Live Adhere to Longer Better Treatment ~40% reduction in mortality Lower incidence of self- Quarterly HCP dosing over 48 months reported GI adverse effects driving >90% verified adher
Slide 27: Agenda: Strengthening Leadership
Agenda The Opportunity The AMVUTTRA Value Proposition Strengthening Leadership Competing in Silencer Class John P. Kennedy Senior Vice President, TTR Franchise Commercialization Lead Anticipating Stabilizer Genericization Mark Soued Senior Vice President, Head of U.S. & TTR Lead Unlocking Category G
Slide 28: Sustaining Leadership in the Silencer Class
Sustaining Leadership in the Silencer Class
Slide 29: In hATTR-PN, Already Leading in Silencer Competition
In hATTR-PN, Already Leading in Silencer Competition In U.S., before CM label expansion Category Growth Accelerated 62% Growth Total Patients (k) Jan ‘24 – March ‘25 AMVUTTRA 2.5 captured ~80% of 2.0 Wainua all scripts Launch 1.5 and >70% 1.0 of new starts 0.5 Jan’23 Jan’24 Mar’25 AMVUTTRA & ONPATTR
Slide 30: Growing Real World Experience
Treatment Effect of AMVUTTRA on Background Stabilizer Already Established + Growing Included in AMVUTTRA Real World Experience Product Label These highlights do not include all the information needed to use AMVUTTRA safely and effectively. See full prescribing information for AMVUTTRA.
Slide 31: Favorable Read-Through of Corroborating Silencer Data
Favorable Read-Through of Corroborating Silencer Data When Choosing a Silencer A Large Look for Depth, Duration & Consistency Majority of of Knockdown Effect Cardiologists Believe positive AMVUTTRA Nucresiran combination data for Today for the Future from CARDIO- TTRansform 87% mean TTR >95% mean TT
Slide 32: AMVUTTRA Lays Groundwork Across Payer Environments
AMVUTTRA Lays Groundwork Across Payer Environments AMVUTTRA has broad access as a Medical Benefit Product ~99% ~90% coverage for AMVUTTRA have access to AMVUTTRA as 1L (with no step-through required) Majority pay $0 in out-of-pocket costs
Slide 33: Sustaining Leadership in the Silencer Class
Sustaining Leadership in the Silencer Class Competition Successfully More Depth, duration fuels competing combination & consistency expansion already in data supports of knockdown hATTR-PN class profile Robust and sustained Maintained clear leadership Corroborates HELIOS-B, AMVUTTRA today, category
Slide 34: Anticipating Genericization of the Stabilizer Class
Anticipating Genericization of the Stabilizer Class
Slide 35: Driving Competitive Preference
Establishing Leadership Demand for AMVUTTRA Silencing MOA Ahead of Stabilizer Genericization Before tafamidis LOE Driving Already challenging the 6-year Competitive incumbent for leadership share Building HCP and patient Preference experience and preference
Slide 36: 1L Access Will Remain Following Tafamidis LOE
Maintaining Broad & Durable Access Following tafamidis LOE Alternate MOA 1L Access Will Remain for Stabilizer For Large Segment of Patients Progressors Other Gov’t Commercial Medicare as many as FFS Medicare Advantage 50% of tafamidis patients AMVUTTRA Payer Mix in ATTR-CM Today may progress Source:
Slide 37: Unlocking Dual-MOA Treatment Strategies
A Catalyst to Unlock Dual-MOA Combination Treatment Following tafamidis LOE Unlocking Dual-MOA Treatment Strategies Cardiology Corroborating Generic Stabilizer Accustomed Dual-MOA Data Availability to Dual-MOA Anticipated from Reduces the Cost of Strategies CARDIO-TTRansform Dual-MOA Treatment
Slide 38: Silencer of Choice in a Genericized Stabilizer World
Silencer of Choice in a Genericized Stabilizer World Driving 1L Durable Access Unlocking Dual- Demand & & Patient Need MOA Treatment Preference Years ahead of anticipated Large segment of market to remain Reduced cost of dual-MOA strategies tafamidis LOE 1L accessible Growing body of data supporting
Slide 39: Agenda: Unlocking Category Growth
Agenda The Opportunity The AMVUTTRA Value Proposition Strengthening Leadership Competing in Silencer Class Anticipating Stabilizer Genericization Unlocking Category Growth John P. Kennedy Senior Vice President, TTR Franchise Commercialization Lead
Slide 40: A Strategic Approach to Drive Diagnosis Rate
A Strategic Approach to Drive Diagnosis Rate Diagnosis Awareness Suspicion (confirmed) Nuclear Scintigraphy Noninvasive, acceptable accuracy & accessible
Slide 41: A Strategic Approach to Drive Diagnosis Rate
A Strategic Approach to Drive Diagnosis Rate Diagnosis Awareness Suspicion (confirmed) Nuclear Scintigraphy Noninvasive, acceptable accuracy & accessible
Slide 42: Accelerating our Category Growth Investments
Accelerating our Category Growth Investments A focused, strategic approach Driving Growth in Expanding HCP Patient Awareness Prescriber Base & Engagement in ATTR-CM Enabling Advancing End-to-End AI-Enabled Health Diagnostic System Technology Engagements
Slide 43: Making AMVUTTRA Available Worldwide
Making AMVUTTRA Available Worldwide, Driving Impact & Growth Commercial Strong Submission Access Unlocked Momentum • Launched in Japan, Germany, Austria, UK • Engaging at the public health policy level • • Advancing additional regulatory submissions, and/or pricing and reimbursement negotiations APP
Slide 44: ATTR-CM Category Expansion Creates a Substantial Opportunity
ATTR-CM Category Expansion Creates a Substantial Opportunity U.S. estimated potential 75K treated patients in TTR category by 2030 Source: Internal estimate
Slide 45: We Have Built a Foundation for Durable Growth
We Have Built a Foundation for Durable Growth Driving Patient Provider Preference Access & Network & Utilization Affordability Category growth
Slide 46: Strong Foundation Accelerating the Next Phase of Launch
Strong Foundation Accelerating the Next Phase of Launch Sustained Breadth of Adherence / Category Prescribers Persistence Growth
Slide 47: Q&A
Q&A