Alnylam Pharmaceuticals, Inc. · NASDAQ:ALNY
Alnylam Pharmaceuticals — Investor Presentation (April 2018)
33 slides from Alnylam Pharmaceuticals's investor presentation, April 2018
Slide 1: Corporate Overview
Corporate Overview April 2018 © 2018 Alnylam Pharmaceuticals, Inc. 1
Slide 2: 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. There are a number of important factors that could cause actual results to differ material
Slide 3: RNAi Therapeutics: New Class of Innovative Medicines
RNAi Therapeutics: New Class of Innovative Medicines Clinically Proven Approach with Transformational Potential Nobel Prize-winning science Silence any gene in genome Potent and durable mechanism of action Product engine for sustainable pipeline Now entering commercial stages 3
Slide 4: Alnylam Clinical Development Pipeline
Alnylam Clinical Development Pipeline Focused in 3 Strategic Therapeutic Areas (STArs): Genetic Medicines Cardio-Metabolic Diseases HUMAN BREAKTHROUGH EARLY STAGE LATE STAGE REGISTRATION/ COMMERCIAL Hepatic Infectious Diseases POC1 DESIGNATION (IND or CTA Filed-Phase 2) (Phase 2-Phase 3) COMMERCIAL2
Slide 5: Hereditary ATTR (hATTR) Amyloidosis
Hereditary ATTR (hATTR) Amyloidosis Patisiran Description Mutations in TTR gene lead to deposition of misfolded protein GI: as amyloid, causing multi-system Diarrhea Nausea disease manifestations1 Vomiting CARDIAC: GU: Heart failure Proteinuria Significant morbidity Arrhythmia Kidney failure UTI and
Slide 6: Phase 3 APOLLO Study Design
Phase 3 Study Design Randomized, Double-Blind, Placebo-Controlled Study in hATTR Amyloidosis Patients with Polyneuropathy Patient Population Patisiran Primary Endpoint 2:1 RANDOMIZATION 0.3 mg/kg • Change in mNIS+7 from baseline at 18 months • hATTR amyloidosis: IV q3W* any TTR mutation, Secondary S
Slide 7: Phase 3 Study Results
Phase 3 Study Results Patisiran Met Primary and all Secondary Endpoints Placebo Patisiran mNIS+7 Worsening Norfolk-QOL Worsening 35 20 LS mean (SEM) ∆Norfolk-QOL from baseline LS mean (SEM) ∆mNIS+7 from baseline 30 15 25 20 10 15 5 10 p=1.10 x 10-10 5 0 p=9.26 x 10-24 0 -5 -5 -10 -10 Improvement Bas
Slide 8: Phase 3 Study Results: Cardiac Subpopulation
Phase 3 Study Results Patisiran Met Key Exploratory Endpoints in Cardiac Subpopulation* Placebo Patisiran Biomarker Echocardiographic Functional NT-proBNP LV Wall Thickness Longitudinal Strain 10MWT Worsening Worsening Worsening Improvement 350 0.12 1.5 0.4 250 0.3 Mean ∆10-MWT gait speed from basel
Slide 9: Phase 3 Study Results: Safety & Tolerability
Phase 3 Study Results Encouraging Safety & Tolerability Profile Overall, 13 deaths in APOLLO study; no deaths considered related to study drug Type of Adverse Event, Placebo Patisiran • Similar frequency of deaths in patisiran and placebo Number of patients (%) (N=77) (N=148) treatment groups 143 •
Slide 10: hATTR Amyloidosis and APOLLO Assessments
hATTR Amyloidosis and APOLLO Assessments Patisiran Misfolded mutant & wild-type TTR amyloid fibrils in circulation Mutant & wild-type deposit in nerves and tissues TTR in liver of many organs Sensorimotor Nerves Autonomic Nerves Heart • Loss of sensation • Orthostatic hypotension • Heart failure Cli
Slide 11: hATTR Amyloidosis Market Opportunity
hATTR Amyloidosis Market Opportunity Estimated Disease Prevalence • ~50,000 hATTR Estimated Global Breakdown* amyloidosis patients worldwide with some endemic hot-spots • Continuum of ROW** U.S. EUCAN peripheral/autonomic neuropathy and cardiac Prevalence symptoms PN Mixed CM PN Mixed CM PN Mixed CM
Slide 12: Patisiran Pathway to Market
Patisiran Pathway to Market Building a Customer-Centric Organization Only product in hATTR amyloidosis, investigational or approved, to demonstrate disease reversal* Fast Track Orphan Drug Designation Accelerated Assessment Breakthrough Status MAA submitted ☐ J-NDA submission NDA submitted ☐ EMA app
Slide 13: Raising hATTR Awareness and Improving Care
Raising hATTR Awareness and Improving Care Diagnosis, Education, Patient Support, and Access are Key Priorities Diagnosis Education Support Access HCP Website Care Days Expanded Access Program • Local support program in • Providing expanded • Started 2014, expanded partnership with local access to p
Slide 14: ALN-TTRsc02 Opportunity
ALN-TTRsc02 Opportunity Advancing Continued Innovation for Patients with ATTR Amyloidosis Phase 1 Study – Healthy Volunteers -40 1.4 Mean [+/-SEM] TTR Knockdown Placebo (N=20) 5mg (N=6) -20 1.2 25mg (N=6) 50mg (N=6) Relative to Baseline (%) 100mg (N=6) 300mg (N=6) Mean max TTR KD of 97.1%; 1.00 ~80%
Slide 15: ALN-TTRsc02 Market Opportunity
ALN-TTRsc02 Market Opportunity* Potential for Significant Expansion in ATTR Amyloidosis hATTR Asymptomatic Wild-type amyloidosis hATTR carriers ATTR amyloidosis patients 15 *Intended to be illustrative and not intended to represent specific estimates of patient numbers
Slide 16: Acute Hepatic Porphyrias
Acute Hepatic Porphyrias Givosiran Description Family of ultra-rare orphan diseases causing incapacitating and potentially fatal attacks, leading to frequent hospitalizations and chronic pain Severe, burning pain Weakness, in abdomen, chest, numbness, back respiratory failure Predominantly female, c
Slide 17: Givosiran Interim Phase 1 Study Results
Givosiran Interim Phase 1 Study Results* Randomized, Double-Blind, Placebo-Controlled Study in Recurrent Attack Porphyria Patients 73% Mean Decrease in Annualized Attack Rate Run-in Period Run-in Treatment Period Treatment Givosiran Compared to Placebo 160 Givosiran – Patient 3 (2.5 mg/kg q3M) mmol/
Slide 18: Givosiran Phase 3 Study Design
Phase 3 Study Design Randomized, Double-Blind, Placebo-Controlled Study in Acute Hepatic Porphyria Patients N ~ 75 Givosiran Primary Endpoint 1:1 RANDOMIZATION SC qM • Attacks requiring Patient Population 2.5 mg/kg hospitalization, urgent • Age ≥ 12 years care visit, home IV hemin at 6 months Open-L
Slide 19: Interim Analysis for Potential Accelerated Approval
Phase 3 Study Interim Analysis for Potential Accelerated Approval Alignment with FDA that reduction of urinary ALA is reasonably likely to predict clinical benefit • Interim analysis with ~30 patients after 3 mo dosing; expect topline data in mid-2018 • Expect NDA submission in Late 2018 and potenti
Slide 20: Givosiran Market Opportunity
Givosiran Market Opportunity Givosiran has potential to address significant Initial opportunity in unmet needs recurrent population • Current treatment options inadequate Potential for further expansion • 65% of patients have chronic symptoms during and between attacks Variegate porphyria Significan
Slide 21: Other Programs to Watch
Other Programs to Watch 21
Slide 22: Hemophilia and Rare Bleeding Disorders: Fitusiran
Hemophilia and Rare Bleeding Disorders (RBD) DURABILITY Fitusiran Monthly SC fixed dose regimen Description Fitusiran Phase 2 OLE Study in Inhibitor Patients* Genetic deficiency results in inability to generate thrombin and stop bleeding, 40 38 leading to recurrent bleeds into joints, 35 muscles, an
Slide 23: Hypercholesterolemia: Inclisiran
Hypercholesterolemia Inclisiran DURABILITY Biannual SC dose Description regimen Highly prevalent disease caused by Inclisiran ORION-1 Phase 2 Study* elevated levels of LDL-C that increase risk of atherosclerotic cardiovascular disease (ASCVD) PATIENT POPULATION ~31 million in U.S. have LDL-C levels
Slide 24: Primary Hyperoxaluria Type 1: Lumasiran
Primary Hyperoxaluria Type 1 Lumasiran (ALN-GO1) Lumasiran Phase 1/2 Study; Initial Low-Dose Cohort (1 mg/kg, q4W) Description Lumasiran Rare autosomal recessive 2.2 Placebo Delayed initial dosing of lumasiran in patient randomized to placebo disorder of increased oxalate 2.0 24h Urine Oxalate corre
Slide 25: Complement-Mediated Diseases: Cemdisiran
Complement-Mediated Diseases Cemdisiran (ALN-CC5) Description Cemdisiran Phase 1/2 Study in Healthy Volunteers Numerous debilitating diseases -40 50 mg (N=3) 600 mg (N=3) Mean (+/- SEM) C5 knockdown relative to 200 mg (N=3) 900 mg (N=3) caused by abnormal complement -20 400 mg (N=3) Placebo (N=5) ac
Slide 26: Alpha-1 Antitrypsin Deficiency Associated Liver Disease
Alpha-1 Antitrypsin (AAT) Deficiency Associated Liver Disease ALN-AAT02 Description ALN-AAT Preclinical Study in Tg-PiZ mice1 Orphan disease where mutant Nucleus AAT misfolds and aggregates in hepatocytes, leading to liver cirrhosis PATIENT POPULATION2 ~12,000 worldwide Placebo-Treated ALN-AAT-Treat
Slide 27: Nonalcoholic Steatohepatitis (NASH)
Nonalcoholic Steatohepatitis (NASH) HSD17B13 Target Description HSD17B13 as a novel target1 Progressive disease characterized by hepatic fat buildup and inflammation, potentially leading to cirrhosis PATIENT POPULATION2 TA/TA (Variant) T/T (WT) Better Better >9 million adults in U.S. • Hepatocyte ex
Slide 28: UK Biobank Consortium
UK Biobank Consortium World-leading effort to connect genotype to full medical records for phenome-wide association studies • Goal to generate 500K exome sequences linked to medical records by end-2019 – 50K exomes sequenced to date • Consortium members receive broad, ongoing access to UK Biobank da
Slide 29: Guidance and Goals
Guidance and Goals 29
Slide 30: STArs, Marketed Products and Clinical Programs
ZL Alnylan. 3 STArs 3 Marketed Products 10 Clinical Programs 4 Late Stage Programs
Slide 31: Alnylam 2018 Goals
Alnylam 2018 Goals 2018* *Early is Q1-Q2, Mid is Q2-Q3, and Late is Q3-Q4 Early Mid Late Additional APOLLO Phase 3 data FDA approval U.S. launch PATISIRAN J-NDA submission (hATTR Amyloidosis) EMA approval EU launch Additional ROW submissions Additional Phase 1/Phase 2 OLE data GIVOSIRAN ENVISION Pha
Slide 32: Financial Summary and Guidance
Financial Summary and Guidance 2017 Q4 Financial Results 2018 Financial Guidance • Cash $1.73B • Cash, including restricted cash and – Includes $30.0M in restricted restricted investments of ~$1.0B investments • Annual Non-GAAP Operating • GAAP Revenues $37.9M Expenses • Total GAAP Operating Expense
Slide 33: Challenge Accepted
To those who say “impossible, impractical, unrealistic,” we say: CHALLENGE ACCEPTED © 2018 Alnylam Pharmaceuticals, Inc. 33
Alnylam Pharmaceuticals — Investor Presentation (April 2018) on 6ix