Alnylam Pharmaceuticals, Inc. · NASDAQ:ALNY
Alnylam Pharmaceuticals — Investor Day (October 2024)
87 slides from Alnylam Pharmaceuticals's investor day presentation, Oct 9, 2024
Slide 1: TTR Investor Day
TTR Investor Day October 9, 2024 © 2024 Alnylam Pharmaceuticals, Inc. 1
Slide 2: Leadership Here Today
Leadership Here Today Yvonne Greenstreet, MBChB Pushkal Garg, M.D. Jeff Poulton Tolga Tanguler Chief Executive Officer Chief Medical Officer Chief Financial Officer Chief Commercial Officer John Vest, M.D. John P. Kennedy Mark Soued Jason Gidelson Christine Lindenboom Senior Vice President, Vice Pre
Slide 3: TTR Investor Day Agenda
TTR Investor Day Agenda 8:30-8:45 AM Alnylam: A Leading Global Biotech Yvonne Greenstreet 15 min 8:45-9:05 AM ATTR-CM Disease & Unmet Needs Dr. Ahmad Masri 20 min 9:05-9:30AM The Promise of Vutrisiran for TTR Patients John Vest 25 min 9:30-9:50 AM Q&A Pushkal Garg (moderator) 20 min 9:50-10:15 AM Br
Slide 4: Event Logistics
Event Logistics Event Two moderated Replay will be scheduled Q&A sessions available on to end at during the Investors Page ~12:00 p.m. ET meeting of our website later today 4
Slide 5: 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 6: Alnylam: A Leading Global Biotech
Alnylam: A Leading Global Biotech Yvonne Greenstreet, MBChB Chief Executive Officer 6
Slide 7: Key Themes You'll Hear Today
Key Themes You’ll Hear Today Alnylam is at a Major Inflection Point High Unmet Need in ATTR-CM A devastating, progressive disease with a large, addressable, and growing market AMVUTTRA Poised to Be the Standard of Care for 1L Patients in ATTR-CM Strong clinical evidence in a population reflective of
Slide 8: Leading Biotech Profile
Leading Biotech Profile $ Outstanding Robust and Leading Commercial Strong Financial R&D Productivity High-Yielding Pipeline Capabilities Position Validated RNAi 15 >60 >$2.6B class of medicines clinical programs countries with commercial cash balance, presence through direct based on performance 5
Slide 9: Vutrisiran sNDA for ATTR-CM Submitted to FDA
Priority Review Voucher to Vutrisiran sNDA accelerate FDA review period for ATTR-CM Submitted to FDA Additional global regulatory submissions – late 2024 9 Note: Vutrisiran is an investigational therapeutic in development for ATTR-CM, and efficacy and safety in this patient population has not been e
Slide 10: Flagship Franchises & Category Leadership Catalyze Growth
Flagship Franchises & Category Leadership Catalyze Growth Poised for Leadership in TTR 10 Note: The safety and efficacy of AMVUTTRA (vutrisiran) for the treatment of ATTR amyloidosis with cardiomyopathy have not been established or evaluated by the FDA, EMA or any other health authority.
Slide 11: Marc
Marc Living with wild-type ATTR amyloidosis with cardiomyopathy 11
Slide 12: ATTR-CM Disease & Unmet Needs
ATTR-CM Disease & Unmet Needs 12
Slide 13: Guest Speaker Dr. Ahmad Masri
Guest Speaker Dr. Ahmad Masri, M.D., M.S. Associate Professor of Medicine, Division of Cardiovascular Medicine, Oregon Health & Science University Dr. Masri heads the Cardiomyopathy Section, the Cardiac Amyloidosis Program, and the Hypertrophic Cardiomyopathy Center at the Oregon Health & Science Un
Slide 14: ATTR-CM
ATTR-CM Ahmad Masri, MD MS Cardiomyopathy Section Head Director, Cardiac Amyloidosis Program Director, Hypertrophic Cardiomyopathy Center Associate Professor of Medicine Oregon Health & Science University 14
Slide 15: Disclosures
Disclosures • Research Grants from Pfizer, Ionis, Attralus, and Cytokinetics. • Fees from Cytokinetics, BMS, Eidos/BridgeBio, Pfizer, Ionis, Lexicon, Attralus, Alnylam, Haya, Alexion, Akros, Lexeo, Prothena, BioMarin, AstraZeneca, and Tenaya. 15
Slide 16: Transthyretin Amyloid Cardiomyopathy
Transthyretin Amyloid Cardiomyopathy 16 Masri A et al. J Nucl Med. 2020;61:965-970.
Slide 17: ATTR-CM is Prevalent in Heart Failure and in Aortic Stenosis
ATTR-CM is Prevalent in Heart Failure and in Aortic Stenosis Gonzalez-Lopez E et al. Eur Heart J. 2015;36:2585-94. Hahn VS et al. JACC HF. 2020;8:712–724. Castano A et al. Eur Heart J. 2017;38:2879-2887., 17
Slide 18: Systematic Screening Strategy is Better Than Clinical Evaluation
Systematic Screening Strategy is Better Than Clinical Evaluation 18 AbouEzzeddine OF et al. JAMA Cardiol. 2021;6:1267-1274.
Slide 19: Carpal tunnel biopsy amyloid findings
• 10% of biopsies from carpal tunnel release surgery had amyloid deposits • 2% had hereditary ATTR • 2% had cardiac disease • 3% were initiated on therapy 19 Sperry BW et al. J Am Coll Cardiol. 2018;72:2040-2050.
Slide 20: V122I (p.V142I)
V122I (p.V142I) • First described in 1988 in an African-American man • Unique – predominantly in patients with African descent • Age-dependent autosomal dominant • Prevalence of ~3.4% of African Americans • 1.6 Million carriers* • ~150,000, aged ≥65 years* *Estimation based on US Census. 20 Chandras
Slide 21: TTR Targets of Therapy
TTR Targets of Therapy • Patisiran* • Diflusinal** • NI006/ALXN2220 • Vutrisiran • Tafamidis*** • AT-02 • Eplontersen • Acoramidis • PRX004/NNC6019 • Inotersen • NTLA-2001 21 Ruberg et al. JACC 2019 (modified)
Slide 22: Early Diagnosis is Essential
Early Diagnosis is Essential 22 Maurer et al. NEJM 2018
Slide 23: Unmet Need to Truly Achieve Early Diagnosis
Unmet Need to Truly Achieve Early Diagnosis 23 Tini et al. ESC HF 2024
Slide 24: Concurrent AS+CA Associated with Increased Risk of Death
Concurrent AS+CA Was Associated with An Increased Risk of Death and HF-related Hospitalization Compared with AS Alone 24 Masri A et al. J Am Coll Cardiol. 2022;80 (12_Supplement): B175.
Slide 25: Significant Unmet Need on Tafamidis in ATTR-ACT and OLE
Significant Unmet Need on Tafamidis in ATTR-ACT and OLE 25 Elliott et al. Circ HF 2022
Slide 26: Real World Experience with Tafamidis and the Changing Natural History
Real World Experience with Tafamidis and the Changing Natural History 26 Masri et al. HFSA 2023
Slide 27: Monitoring ATTR-CM Progression
Monitoring ATTR-CM Progression Mortality NT-proBNP CV Hospitalizations Troponin Urgent visits TTR level Diuretics Intensification KCCQ NYHA class 6MWT 27
Slide 28: Future Goals in ATTR-CM
Future Goals in ATTR-CM • Better disease control • Improved survival and decreased hospitalizations • Improved function and quality of life • Addressing unintentional weight loss • Disease regression • Ongoing need for longer term studies 28
Slide 29: Conclusions
Conclusions • While ATTR-CM is being transformed through earlier recognition, better overall management, and targeted therapy such as tafamidis, there remains a significant unmet need. • New diagnostic approaches and new therapies open the door to further improving patients’ outcomes. 29
Slide 30: The Promise of Vutrisiran for TTR Patients
The Promise of Vutrisiran for TTR Patients John Vest, M.D. SVP, TTR Global Development Lead 30
Slide 31: RNAi Therapeutic Hypothesis in ATTR Amyloidosis
RNAi Therapeutic Hypothesis in ATTR Amyloidosis Silencing TTR Gene Expression to Address Underlying Cause of Disease Vutrisiran is a RNAi therapeutic targeting hepatic TTR production; dosing 25 mg once every Vutrisiran hATTR wtTTR 3 months Characterized by rapid Misfolded TTR knockdown Approved for
Slide 32: Profile of RNAi Therapeutics in Hereditary ATTR with Polyneuropathy
Profile of RNAi Therapeutics in Hereditary ATTR Amyloidosis with Polyneuropathy Transformational Profile in hATTR-PN Percent Change from Baseline in Serum TTR Levels Consistent results observed with both vutrisiran (HELIOS-A) and patisiran (APOLLO) Stabilization or improvement in neuropathy mNIS+7 S
Slide 33: Exploratory Analyses of All-Cause Mortality from APOLLO and APOLLO-B
Exploratory Analyses of All-Cause Mortality from APOLLO and APOLLO-B Previous Data From Patisiran Supported Potential for RNAi to Reduce Mortality APOLLO APOLLO-B Pooled APOLLO and APOLLO-B 12 12 12 10 10 10 Cumulative Mortality (%) Cumulative Mortality (%) Cumulative Mortality (%) 8 8 8 HR = 0.53 H
Slide 34: HELIOS-B Vutrisiran Phase 3 Study Design
Vutrisiran Phase 3 Study Randomized, Double-Blind Outcomes Study in ATTR Amyloidosis Patients with Cardiomyopathy Patient Population Primary Endpoints (N=655) Vutrisiran • Composite outcome of all-cause mortality and 1:1 RANDOMISATION2 • ATTR: wild-type or any TTR variant SC q3M recurrent CV events
Slide 35: HELIOS-B Enrolled Population Reflective of Today's Patient
HELIOS-B Enrolled Population Reflective of Today’s Patient Milder Patients on Substantial Background Therapy; Underscores Magnitude of Treatment Effect and Relevance of Data to Real World Use of Substantial Background Medications Patient Characteristics Real World Data* HELIOS-B ~50% 2002-2006 (n=35
Slide 36: HELIOS-B Enrolled Population Reflective of Today's Patient
HELIOS-B Enrolled Population Reflective of Today’s Patient Milder Patients on Substantial Background Therapy; Underscores Magnitude of Treatment Effect and Relevance of Data to Real World Use of Substantial Background Medications Patient Characteristics Real World Data* HELIOS-B ~50% 2002-2006 (n=35
Slide 37: Favorable Impact Across Sequential Parameters in ATTR-CM
Favorable Impact Across Sequential Parameters in ATTR Amyloidosis with Cardiomyopathy Observed Clinical Benefit Occurs Early and Cascades in a Biologically Rational Manner Rapid TTR Cardiac Functional, Outcomes Knockdown Biomarkers and Health Status, and Benefit Echocardiographic QoL Benefit Improve
Slide 38: Rapid TTR Knockdown and Durable Impact
Rapid TTR Knockdown and Durable Impact TTR Change Over Time in HELIOS-B Vutrisiran Placebo 20 0 -7.9% Median (IQR) % Change (-21.2, 13.4) –20 from Baseline –40 –60 –80 -86.8% (-92.4, -73.3) –100 0 3 6 9 12 15 18 21 24 30 Month Since First Dose TTR % change at Month 30: Mean (SD): placebo -1.98 (35.4
Slide 39: Vutrisiran Maintained Relative Stability of NT-proBNP and Troponin I
OVERALL POPULATION Vutrisiran Maintained Relative Stability of NT-proBNP and Troponin I Compared with Placebo Favorable Treatment Effect Observed as Early as 6 Months on Exploratory Endpoints, and Grew Over Time 32% Relative Reduction for Both Biomarkers at Month 30 NT-proBNP Troponin I Ratio (Vutri
Slide 40: Vutrisiran Improved Cardiac Structure and Function
OVERALL POPULATION Vutrisiran Improved Cardiac Structure and Function Exploratory Echocardiographic Assessments at M30 Provide Supportive Evidence of Disease-Modifying Effect Cardiac Structure Systolic Function Diastolic Function Absolute Global Mean LV Wall Thickness E/e’ Ratio Longitudinal Strain
Slide 41: Favorable Impact on Multiple Measures of Disease Progression
OVERALL POPULATION Favorable Impact on Multiple Measures of Disease Progression Preserved Functional Capacity, Health Status, and Quality of Life over 30 Months; Statistically Significant Impact Relative to Placebo Median Change over Time (Observed) Overall Population 0 Change from Baseline 6-MWT, m
Slide 42: Reduction in All-Cause Mortality and Recurrent CV Events
OVERALL POPULATION Reduction in All-Cause Mortality and Recurrent CV Events Time to First CV Event or All-Cause Mortality1 Overall population (N = 654) Freedom From CV Events or ACM, % 100 Primary endpoint: all-cause mortality and recurrent CV events up to month 36 (LWYY) 90 HR (95% CI) 0.718 (0.555
Slide 43: Consistent Efficacy Across All Prespecified Subgroups
OVERALL POPULATION Consistent Efficacy Across All Prespecified Subgroups Magnitude of Treatment Effect and Outsized Benefit in Key Subgroups Highlight Relevance to Today’s Patients and Supports First-Line Positioning Composite Outcome of All-Cause Mortality & Recurrent CV Events Secondary Endpoint o
Slide 44: Significant Outcomes Benefit with Vutrisiran Monotherapy
Significant Outcomes Benefit with Vutrisiran Monotherapy and Favorable Trends in Baseline Tafamidis Subgroup Monotherapy Population 33% 100 Time to First CV Event or All-Cause Mortality1 100 Time to All-Cause Mortality1 35% Freedom From CV Events or ACM, % reduction in reduction in Adjusted Survival
Slide 45: Key Takeaways From HELIOS-B
Key Takeaways From HELIOS-B In a population reflective of today’s patients, on substantial background therapy, HELIOS-B demonstrated profound benefit on outcomes Clinical effect seen early, starting with effects on well-established biomarkers predictive of outcomes in real world and within HELIOS-B
Slide 46: Putting It All Together; Vutrisiran Well-Positioned for 1L Use
Putting It All Together; Vutrisiran Well-Positioned for 1L Use HELIOS-B results were observed in a population reflective of today’s patients on substantial background therapy Magnitude of benefit was profound Trends of substantial benefit observed in patients on background tafamidis, highlighting un
Slide 47: Q&A Chat With Clinical Leadership and ATTR-CM Expert
Q&A Chat With Clinical Leadership and ATTR-CM Expert Pushkal Garg, M.D. Dr. Ahmad Masri, John Vest, M.D. Executive Vice President, M.D., M.S. Senior Vice President, Chief Medical Officer TTR Global Oregon Health & Science Development Lead MODERATOR University 47
Slide 48: TTR Investor Day
TTR Investor Day October 9, 2024 © 2024 Alnylam Pharmaceuticals, Inc. 48
Slide 49: Building a Flagship Franchise in ATTR-CM
Building a Flagship Franchise in ATTR-CM Tolga Tanguler EVP, Chief Commercial Officer 49
Slide 50: Large and Growing Category with Significant Unmet Need
Large and Growing Category with Significant Unmet Need Growing Category with Rapidly Improving Dx Large and Untapped Opportunity ATTR-CM Diagnoses >300K patients globally3 ~10x ~80% ATTR-CM patients undiagnosed globally3 growth in Diagnoses since 20191 New entrants expected to further grow the Diagn
Slide 51: Demonstrated Market Leadership in hATTR-PN
Demonstrated Market Leadership in hATTR-PN Alnylam TTR Product Sales >$1,200M Established hATTR-PN Category in U.S. +53% CAGR ’19-’23 $909M >45% YoY CAGR between 2019-2023 $651M $475M $306M Competed Effectively in EU & JP $166M >80% Estimated share of the hATTR-PN 2019 2020 2021 2022 2023 2024E mark
Slide 52: We Know What it Takes to Succeed
We Know What it Takes to Succeed $ Multi-Billion Market-Leading The Right Patient-Centric Market Potential Profile Talent Approach Organizational Focus and TTR Experience 52
Slide 53: We Have Built a World-Class Leadership Team
We Have Built a World-Class Leadership Team Joining us here today: Successful John Kennedy biopharma TTR Franchise leaders, with proven Commercialization Lead global experience Mark Soued Head of U.S. & TTR Lead Broad Leadership roles in therapeutic category-defining, area expertise multi-billion Ja
Slide 54: We Are On a Path to Leadership
We Are On a Path to Leadership Large, untapped and growing category with significant unmet need AMVUTTRA is poised to become the standard of care for first line patients in ATTR-CM1 Our success and strong leadership in hATTR-PN position us to be highly competitive in ATTR-CM We have a deep focus on
Slide 55: Driven by Patient Needs
Driven by Patient Needs John Kennedy TTR Franchise Commercialization Lead 55
Slide 56: ATTR-CM Market is Large, Growing and Underserved
ATTR-CM Market is Large, Growing and Underserved with Unmet Needs Across Three Patient Segments New to Treatment Stabilizer Progressors Undiagnosed Global Est. Size1 ~18K ~20K ~80% New to Treatment, Treatment Progressors Undiagnosed Patients Annually (and Growing) (Diagnosis/Treatment Rate Improving
Slide 57: Establish AMVUTTRA as First-Line Choice for Patients New to Treatment
Establish AMVUTTRA as First-Line Choice in ATTR-CM for Patients New to Treatment What We Know • >50% YoY growth in volume of ATTR-CM patients treated with approved therapy today1 • Largest & fastest growing patient segment aligned with HELIOS-B profile (milder disease)2 New to Treatment • ~20-30% mi
Slide 58: HELIOS-B Delivers First-Line Potential for AMVUTTRA
HELIOS-B Delivers First-Line Potential for AMVUTTRA Clinical Considerations Practical Considerations Compelling HELIOS-B Dataset Patient Experience Patients with milder symptoms on substantial background therapy underscore magnitude of 4x ~95% treatment effect and relevance of data to real world dos
Slide 59: Encouraging Cardiologist Response to HELIOS-B
Encouraging Cardiologist Response to HELIOS-B In an Independent Poll of ATTR-CM Treating Cardiologists Across U.S. & EU Based on the HELIOS-B Data Released... Likelihood to Prescribe AMVUTTRA Likelihood to Prescribe AMVUTTRA Data Support AMVUTTRA Becoming for ATTR-CM Patients as 1L Monotherapy for A
Slide 60: Encouraging Cardiologist Response to HELIOS-B
Encouraging Cardiologist Response to HELIOS-B In an Independent Poll of ATTR-CM Treating Cardiologists Across U.S. & EU Based on the HELIOS-B Data Released... Likelihood to Prescribe AMVUTTRA Likelihood to Prescribe AMVUTTRA Data Support AMVUTTRA Becoming for ATTR-CM Patients as 1L Monotherapy for A
Slide 61: Capture Stabilizer Progressors for Switch / Add-On Opportunity
Capture Stabilizer Progressors for Switch / Add-On Opportunity What We Know • ~50% of stabilizer treated patients experienced cardiac worsening* over ~12 mos (median), in recent US claims/EHR analysis (n > 800)1 • Progressor enrollment in APOLLO-B / Patisiran EAP illustrate the unmet need Stabilizer
Slide 62: Drive Earlier Diagnosis Across All Addressable ATTR-CM Patients
Drive Earlier Diagnosis Across All Addressable ATTR-CM Patients What We Know • ~ 10x growth in Diagnosis in US, 2019 – 20231 • Competition accelerates category growth as seen in analogous, under-served specialty treatment categories2 • Alnylam track record driving sustained growth Undiagnosed 53% CA
Slide 63: To Achieve Our Goals, We Must Be Ready to Scale
To Achieve Our Goals, We Must Be Ready to Scale Opportunity How We’ll Get There Establish AMVUTTRA Successful first launch in U.S. is as first-line choice key enabler of early momentum Capture switch / add-on opportunity Drive earlier diagnosis across ATTR-CM patients 63
Slide 64: Unlocking the U.S. Opportunity in ATTR-CM
Unlocking the U.S. Opportunity in ATTR-CM Mark Soued SVP, Head of U.S. & TTR Lead Jason Gidelson VP, U.S. Market Access 64
Slide 65: Three Foundations For a Successful Launch In ATTR-CM
Three Foundations For a Successful Launch In ATTR-CM Access Treatment Patient Selection Support U.S. Launch Strategy Entering ATTR-CM represents a step-up, NOT a giant leap 65
Slide 66: Expanded Field Teams Ready to Establish AMVUTTRA as Preferred 1L Treatment
Expanded Field Teams Ready to Establish AMVUTTRA as Preferred 1L Treatment Across Three Patient Segments Access Treatment Patient Selection Support U.S. Launch Strategy 66
Slide 67: AMVUTTRA Opportunity Spans Three Key Segments
AMVUTTRA Opportunity Spans Three Key Segments ~150K Prevalent Patients in the U.S. • ~5-10K ATTR-CM patients initiating treatment annually at increasing rate New To 1 • AMVUTTRA well positioned to compete as 1L choice Treatment • Fastest segment to unlock • ~15-25K patients currently on stabilizers
Slide 68: Field Teams Expanded to Deliver 100% Coverage At Launch
Field Teams Expanded to Deliver 100% Coverage At Launch FROM TO Today (PN) At Launch ~3,700 ~65% 100% HCPs treating ~95% of patient ALNY Coverage ALNY Coverage population (due to hATTR-PN diagnostic pathways) ~170 ~45% 100% Health systems accounting for ~80% of potential Rx volume ALNY Coverage ALNY
Slide 69: We Expect to Maintain Favorable Access in ATTR-CM
We Expect to Maintain Favorable Access in ATTR-CM Access Treatment Patient Selection Support U.S. Launch Strategy 69
Slide 70: In hATTR-PN, AMVUTTRA Maintains Broad Access
In hATTR-PN, AMVUTTRA Maintains Broad Access AMVUTTRA Has >99% Coverage1,2 Other Government Payers AMVUTTRA has ~9% maintained favorable Medicare Fee coverage since Commercial ~23% ~40% For Service launch (Part B) ~70% of AMVUTTRA ~28% patients today pay $0 OOP Medicare Advantage 70 1. Based on DKP
Slide 71: In ATTR-CM, HELIOS-B Provides Compelling Clinical Data
In ATTR-CM, HELIOS-B Provides Compelling Clinical Data Payers First Consider Clinical Data HELIOS-B Clinical Benefits and Then Cost in Coverage Policies1 Higher Clinical Efficacy There is an unmet need in ATTR-CM given limited Importance treatment options Safety HELIOS-B demonstrated that treatment
Slide 72: In ATTR-CM, AMVUTTRA Expected to Have Widespread Coverage
In ATTR-CM, AMVUTTRA Expected to Have Widespread Coverage Expected Future State Medicaid/Other ~5% Medicare FFS Payer mix in Commercial ~20% ATTR-CM expected ~38% to be similar to hATTR-PN, and consistent with current ATTR-CM ~37% dynamics Medicare Advantage Sources (non-exhaustive): Komodo and Alny
Slide 73: Most AMVUTTRA Patients Expected to Pay $0 Out of Pocket
In ATTR-CM, Most AMVUTTRA Patients Expected to Pay $0 Out of Pocket1,2 Expected Future State Medicaid/Other Median OOP $0 ~5% Medicare FFS Median OOP $0 (due to Medigap) Commercial Median OOP $0 ~20% (due to copay card) ~38% ~37% Medicare Advantage Median OOP ~$3,500 (ineligible for Medigap or copay
Slide 74: Inflation Reduction Act Has Important Implications For Part D
Inflation Reduction Act Has Important Implications For Part D Part D Part B Patient $2,000 Patient No Copay per year max Copay change2 Payer 4X Payer No Liability Increase1 Liability change 1. The IRA increases health plan liability in the catastrophic coverage phase from 15% to 60% of the drug cost
Slide 75: Existing Buy & Bill Network Will Be Leveraged to Scale
Existing Buy & Bill Network For AMVUTTRA in hATTR-PN Will Be Leveraged to Scale In ATTR-CM1 Treatment sites for… hATTR-PN ATTR-CM Group Practices & Clinics Most prescribers are affiliated (~5%) with, or referring to, treatment sites that buy and bill AMVUTTRA In the Home (~25%) ~900 Specialty Infusi
Slide 76: Robust Patient Support Is Essential to Access and Stay on Therapy
Our Robust Patient Support Is Essential to Ensure Patients Can Access Therapy and Stay on It Access Treatment Patient Selection Support U.S. Launch Strategy Entering ATTR-CM represents a step-up, NOT a giant leap 76
Slide 77: Robust Patient Services and Quarterly Dosing Support Adherence
Robust Patient Services Capabilities and Quarterly Dosing Will Support Strong Adherence in ATTR-CM Benefit Financial Disease & Caregiver Verification Assistance Product Guides ~95% Education Continuously adherence optimizing today1 our support for (supported by Provided by our dedicated quarterly do
Slide 78: We Are On a Path to Leadership
We Are On a Path to Leadership Large, untapped and growing category with significant unmet need AMVUTTRA is poised to become the standard of care for first line patients in ATTR-CM1 Our success and strong leadership in hATTR-PN position us to be highly competitive in ATTR-CM We have a deep focus on
Slide 79: Q&A Chat With Our Commercial Leadership
Q&A Chat With Our Commercial Leadership Tolga Tanguler John P. Kennedy Mark Soued Jason Gidelson Executive Vice President, TTR Franchise Senior Vice President, Vice President, Chief Commercial Officer Commercialization Lead Head Of U.S. & TTR Lead U.S. Market Access MODERATOR 79
Slide 80: Our Innovative Pipeline in TTR and Beyond
Our Innovative Pipeline in TTR and Beyond Yvonne Greenstreet, MBChB Chief Executive Officer 80
Slide 81: We Are Uniquely Positioned for Long-Term TTR Leadership
We Are Uniquely Positioned for Long-Term TTR Leadership AMVUTTRA Strong Positioned TTR franchise offers a market commercial to win in is built for leading profile, performance with ATTR-CM longevity well-positioned proven successful as a 1L track record treatment1 in hATTR-PN 81 1. Assuming regulato
Slide 82: ALN-TTRsc04 Reinforces Alnylam's Continuous Innovation in TTR
ALN-TTRsc04 Reinforces Alnylam’s Continuous Innovation in TTR ALN-TTRsc04 An Approved RNAi Therapeutic An Approved RNAi Therapeutic An Investigational RNAi for Treatment of Polyneuropathy for Treatment of Polyneuropathy Therapeutic for Potential of hATTR Amyloidosis1 of hATTR Amyloidosis2 Treatment
Slide 83: Expanding TTR Leadership with ALN-TTRsc04
Expanding TTR Leadership with ALN-TTRsc04 Initial Phase 1 Results Support Best-in-Class Profile • Single 300 mg dose resulted in 20 rapid, deep, and durable Mean Serum TTR Knockdown 0 knockdown of serum TTR: • >90% at Day 15 (percent, ± SEM) -20 • 97% at Day 29 -40 • 93% at Day 180 -60 • All doses o
Slide 84: Advancing a Robust and High-Yielding Pipeline of RNAi Therapeutics
Advancing a Robust and High-Yielding Pipeline of RNAi Therapeutics Positioned to Deliver Strong Growth and Innovation Across Multiple Disease Areas and Indications IND-ENABLING PHASE 1 PHASE 2 PHASE 3 APPROVED ONPATTRO® (patisiran) hATTR Amyloidosis with Polyneuropathy AMVUTTRA® (vutrisiran) hATTR A
Slide 85: Driving a Large Multi-Organ Pipeline to Clinic by End of 2025
Driving a Large Multi-Organ Pipeline to Clinic by End of 2025 From Liver Delivery to CNS Human PoC; Now Advancing to Adipose, Muscle, and More CNS 2 new ALNY-led CNS INDs MUSCLE 3+ including partnered programs First ALNY IND by end of 2025 LIVER 5 new ALNY-led liver INDs 10+ including partnered prog
Slide 86: We Have the Key Components for Success
We Have the Key Components for Success Established Leadership Durable Flagship Best-in-Class in hATTR-PN Franchise Team • >80% share in markets with an • Growing ATTR-CM market • Demonstrated success delivering approved competitor global blockbuster products to • Focused TTR team built for execution
Slide 87: Thank You
Thank You © 2024 Alnylam Pharmaceuticals, Inc. 87
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