Alnylam Pharmaceuticals, Inc. · NASDAQ:ALNY
Alnylam Pharmaceuticals — Investor Presentation (May 2014)
38 slides from Alnylam Pharmaceuticals's investor presentation, May 2014
Slide 1: Corporate Overview
Corporate Overview May 2014
Slide 2: Recent Alnylam News
Recent Alnylam News International Symposium on Amyloidosis (April 27-May 1, Indianapolis) Patisiran » Positive initial data from Phase 2 OLE with sustained TTR knockdown at 80% » Natural History results in FAP showing rapid progression of NIS, correlation with disease severity Arteriosclerosis,
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. There are a number of important factors that could cause actual results to differ material
Slide 4: RNA Interference (RNAi)
RNA Interference (RNAi) A New Class of Innovative Medicines RNAi Therapeutics Harness natural pathway » Catalytic mechanism » Mediated by small interfering RNA or “siRNA” Therapeutic gene silencing » Any gene in genome » Distinct mechanism of action vs. other drug classes » Unique opportunities
Slide 5: RNAi Human Translation Achieved
RNAi Human Translation Achieved Multiple Alnylam Clinical Programs; IV and SC Delivery Human Proof of Mechanism: Human Safety and PK ALN-VSP >2,000 Doses administered RNAi-mediated target » Includes >2 years gene cleavage duration confirmed in biopsy Generally well tolerated samples Human Proo
Slide 6: Alnylam 5x15
Alnylam 5x15 TM Focused Product Development Pipeline for Genetic Medicines RNAi therapeutics as genetic medicines In 2011: 5 Key products in clinical development through 2015 Expect to exceed 2011 guidance » 6-7 Clinical-stage products » At least 2 in Phase 3 » 5-6 Human POCs 11 Programs discl
Slide 7: Global Commercialization Strategy for Value Creation
Alnylam 5x15 TM Global Commercialization Strategy for Value Creation Transformational alliance to expand and accelerate global product value Alnylam retains North America and EU » Leads development and commercialization Genzyme obtains ROW and certain additional rights » Includes co-development
Slide 8: Alnylam Development Pipeline
Alnylam Development Pipeline Discovery Development Phase 1 Phase 2 Phase 3 Patisiran (ALN-TTR02) TTR-Mediated Amyloidosis ALN-TTRsc Hemophilia and ALN-AT3 Rare Bleeding Disorders Complement-Mediated Diseases ALN-CC5 Hepatic Porphyrias ALN-AS1 Hypercholesterolemia ALN-PCSsc Alpha-1-Antitrypsin Defici
Slide 9: Transthyretin-Mediated Amyloidosis (ATTR) Program
Transthyretin-Mediated Amyloidosis (ATTR) Program Unmet Need and Product Opportunity RNAi to treat genetic disease ATTR is significant orphan disease » ~50,000 Patients worldwide Clinical pathology » Onset ~40 to >60 yr; fatal within 5-15 years » Two predominant forms – Familial amyloidotic poly
Slide 10: Patisiran (ALN-TTR02)
Patisiran (ALN-TTR02) Familial Amyloidotic Polyneuropathy (FAP) Patisiran in clinical development International Nonproprietary Name designation for ALN-TTR02 = Patisiran (Pa-TEE-sa-ran) Orphan drug status in US/EU Fast track designation by FDA Positive Phase 1 results in human volunteers » D
Slide 11: Patisiran Phase 2 Study Results
Patisiran Phase 2 Study Results Robust knockdown of both wild-type and mutant TTR in ATTR patients Open label, multi-center, multi-dose, dose escalation study Results (n=29) show up to 96% TTR knockdown; 84% and 87% mean TTR knockdown after 1st and 2nd doses in 0.30 mg/kg q3w cohort (p<0.001 vs.
Slide 12: Patisiran Open-Label Extension (OLE) Study
Patisiran Open-Label Extension (OLE) Study FAP patients dosed in Phase 2 trial eligible for Phase 2 OLE study Clinical endpoints evaluated every 6 months for up to 2 years » Clinical endpoints same as APOLLO Phase 3 study » Dosing at 0.30 mg/kg every 3 weeks Study objectives » Primary: Safety an
Slide 13: Patisiran OLE Preliminary Study Results
Patisiran OLE Preliminary Study Results* Sustained TTR Knockdown at 80% Target Level Sustained knockdown of TTR in ATTR patients Initial OLE study results presented at ISA 2014 Results (n=23) showed sustained TTR knockdown at the 80% target level for ~6 months and >8 doses » Blood samples obtain
Slide 14: Phase 3 Trial of Patisiran in FAP
Phase 3 Trial of Patisiran in FAP Randomized, double-blind, placebo-controlled, global study Study Ongoing Sample size and randomization » N=200 » 2:1, Patisiran vs. placebo Key eligibility criteria » V30M and non-V30M FAP » Baseline NIS 10-100 (FAP stages 1 and 2) Treatment regimen » Patisira
Slide 15: ALN-TTRsc
ALN-TTRsc Familial Amyloidotic Cardiomyopathy (FAC) ALN-TTRsc in clinical development Subcutaneous delivery Completed GLP tox studies confirming wide therapeutic index Positive Phase 1 study results » Normal healthy volunteer study in UK Pilot Phase 2 study ongoing Phase 3 start planned fo
Slide 16: ALN-TTRsc Phase 1 Study Results
ALN-TTRsc Phase 1 Study Results Randomized, double-blind, placebo-controlled SAD and MAD study in healthy volunteers Rapid, dose-dependent, consistent, and durable knockdown of serum TTR » Significant knockdown of serum TTR (p<0.01) up to 94% TTR knockdown; Mean knockdown up to 92.4% Generally w
Slide 17: ALN-TTRsc Phase 2 Study
ALN-TTRsc Phase 2 Study Study Design Open-label, multi-dose study in TTR cardiac amyloidosis » Includes patients with FAC and senile systemic amyloidosis (SSA) 25 Patients 5 mg/kg dose (qd x5 load, qw x5 maintenance) Primary Objective Assess safety and tolerability Secondary Objective Obta
Slide 18: Hemophilia and Rare Bleeding Disorders Program
Hemophilia and Rare Bleeding Disorders Program Unmet Need and Product Opportunity RNAi to treat hemophilia and rare bleeding disorders (RBD) Hemophilias are recessive X-linked monogenic bleeding disorders » Hemophilia A: loss of function in Factor VIII – >40,000 Patients in EU/US » Hemophilia B: l
Slide 19: Antithrombin and ALN-AT3 Program
Antithrombin and ALN-AT3 Program Intrinsic system Extrinsic system Antithrombin (AT) is genetically Hemophilia B FVIIa FVII FX defined target FIX FIXa AT is key natural anticoagulant Hemophilia A » Inactivates factors Xa and thrombin FVIII FVIIIa » Attenuates thrombin generation FXa AT AT Human
Slide 20: Genetic Validation for ALN-AT3
Genetic Validation for ALN-AT3 Co-Inheritance of Type 3 VWD and AT Deficiency Human genetic data support targeting AT for treatment of hemophilia and rare bleeding disorders Sib Sib ● Type 3 von Willebrand disease (VWD) is 1 2 severe genetic bleeding disorder ● Recently reported study of two Type 3
Slide 21: ALN-AT3 Pre-Clinical Efficacy
ALN-AT3 Pre-Clinical Efficacy Potent AT Knockdown and Normalization of Thrombin Generation ALN-AT3 achieves potent AT knockdown and fully corrects thrombin generation in non-human primates (NHP) Weekly SC doses for >5 months result in potent, dose-dependent, and durable AT knockdown In NHP hemop
Slide 22: ALN-AT3 Pre-Clinical Efficacy
ALN-AT3 Pre-Clinical Efficacy Potent AT Knockdown and Normalization of Thrombin Generation ALN-AT3 achieves potent AT knockdown and fully corrects thrombin generation in non-human primates (NHP) Weekly SC doses for >5 months result in potent, dose-dependent, and durable AT knockdown In NHP hemop
Slide 23: ALN-AT3 Phase 1 Study
ALN-AT3 Phase 1 Study Part Dose-escalation Study in Two Parts A Part Study Design B Study Design Randomized, single-blinded, Open-label, MAD study in placebo-controlled SAD study in subjects with moderate to severe healthy volunteers hemophilia A or B (N=up to 18) Max allowable knockdown of 40
Slide 24: Complement Disease Program
Complement Disease Program Unmet Need and Program Opportunity Complement-Mediated Diseases Excessive complement activity drives disease pathophysiology in many indications » Paroxysmal nocturnal hemoglobinuria (PNH) » Atypical hemolytic uremic syndrome (aHUS) » Neuromyelitis optica (NO) » Many oth
Slide 25: Complement C5 and ALN-CC5 Program
Complement C5 and ALN-CC5 Program Alternative Pathway Classical Pathway Lectin Pathway Initiation C3 C1 Complement C5 is genetically C3 validated target C4 and C2 Key component of terminal pathway C3 Convertase Factor B C3bBb C4bC2b » C5 cleavage releases C5a; initiates membrane attack complex (MA
Slide 26: ALN-CC5 Pre-Clinical Efficacy
ALN-CC5 Pre-Clinical Efficacy Potent C5 Knockdown and Hemolytic Activity Inhibition Potent and durable knockdown of complement C5 with SC dosing in non-human primates Potent dose-dependent C5 knockdown up to 98% » Mean knockdown of 97.5% (p<0.001) with effects lasting weeks after last dose » Confi
Slide 27: ALN-CC5 Pre-Clinical Efficacy
ALN-CC5 Pre-Clinical Efficacy Potent C5 Knockdown and Hemolytic Activity Inhibition Potent and durable knockdown of complement C5 with SC dosing in non-human primates Potent dose-dependent C5 knockdown up to 98% » Mean knockdown of 97.5% (p<0.001) with effects lasting weeks after last dose » Confi
Slide 28: Additional Programs
Alnylam 5x15 TM Additional Programs Acute Intermittent Porphyria AAT Deficiency Associated Liver Disease Beta-Thalassemia and Loss of function mutations in Alpha-1-antitrypsin (AAT) deficiency Iron-Overload Disorders porphobilinogen deaminase (PBGD) associated with lung and liver disease Need
Slide 29: Cardio-Metabolic Programs
Cardio-Metabolic Programs Hypercholesterolemia Mixed Hyperlipidemia and Severe Hypertriglyceridemia Elevated LDL-C validated risk Mixed hyperlipidemia is genetic disease with high levels of factor cholesterol and triglycerides >500,000 Patients with severe Severe hypertriglyceridemia include
Slide 30: ALN-PCSsc Pre-Clinical Efficacy in NHP
ALN-PCSsc Pre-Clinical Efficacy in NHP Potent and Durable PCSK9 Knockdown and LDL-C Lowering Highly durable PCSK9 knockdown and LDL-C reduction with single SC dose ALN-PCSsc employs ESC-GalNAc conjugate delivery platform Up to 96% PCSK9 knockdown and up to 77% LDL-C lowering in absence of statin
Slide 31: HBV Program
HBV Program Plasma Viral Load (bDNA) siRNA (mg/kg) 0.125 0.25 0.50 1 0 (relative to average pre-dose) Log10 Δ Viral Load -1 Chronic HBV infection is significant WW problem -2 400M Patients chronically infected WW -3 » 1-2M in US -4 A C Clinical manifestations severe B D Chronic inflammation lead
Slide 32: Alnylam 5x15 Strategy
TM Alnylam 5x15 Strategy A Reproducible and Modular Path for Genetic Medicines 2. POC achieved in Phase 1 Blood-based biomarker with strong disease correlation » e.g., Serum TTR, thrombin GCCCCUGGAGGG generation, hemolytic activity, LDL-C, HBsAg levels 3. Definable path to approval and market Es
Slide 33: Financials and Goals
Financials and Goals ay ZLAlnylam,
Slide 34: Financial Summary
Financial Summary 2014 Q1 Financial Results Cash >$1B GAAP Revenues $8.3M » Takeda, Monsanto, The Medicines Company and others Total GAAP Operating Expenses ~$277M » Research and Development Expense $43.8M » One-time charge for In-Process R&D Expense $224.7M – For acquisition of Sirna RNAi ass
Slide 35: Updated Alnylam 5x15 Pipeline Guidance
Updated Alnylam 5x15 Pipeline Guidance 6-7 Clinical Programs, at Least 2 in Phase 3, and 5-6 Human POC by End ’15 2014 2015 Subsequent 1-3 Years Patisiran Phase 2 OLE D D D TTR-FAP Human POC Phase 3 FAP D Phase 3 ALN-TTRsc Pilot Phase 2 D Phase 3 FAC TTR-FAC D Phase 3 Human POC ALN-AT3 Phase 2/3
Slide 36: Alnylam 2014 Goals
Alnylam 2014 Goals Pipeline Goals 2014* Early Mid Late APOLLO Phase 3 Accrual Patisiran (ALN-TTR02) Phase 2 OLE Accrual TTR-FAP Initial Phase 2 OLE data Phase 2 OLE data ALN-TTRsc Phase 2 FAC data Phase 2 OLE start TTR-FAC Phase 3 FAC start ALN-AT3 Phase 1 SAD start Phase 1 MAD start Initial P
Slide 37: Select Scientific and Clinical Meetings
Select Scientific and Clinical Meetings Early to Mid ’14 International Symposium on Amyloidosis Patisiran » April 27-May 1 in Indianapolis, IN Arteriosclerosis, Thrombosis and Vascular Biology ALN-PCSsc » May 1-3 in Toronto, Canada Digestive Disease Week ALN-AAT » May 4-6 in Chicago, IL Worl
Slide 38: Thank You
Thank You www.alnylam.com
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