Alnylam Pharmaceuticals, Inc. · NASDAQ:ALNY
Alnylam Pharmaceuticals — Investor Presentation (April 2014)
37 slides from Alnylam Pharmaceuticals's investor presentation, April 2014
Slide 1: Corporate Overview
Corporate Overview April 2014
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: RNA Interference (RNAi): A New Class of Innovative Medicines
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 4: 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 5: 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 9 Programs disclo
Slide 6: 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 7: Alnylam 5x15 Development Pipeline
Alnylam 5x15 Development Pipeline TM 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-Antitrypsi
Slide 8: Alnylam 5x15 Development Pipeline: Delivery Technologies
Alnylam 5x15 Development Pipeline TM Delivery Technologies 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-PC
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=28) 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)
Slide 12: Patisiran Safety and Tolerability
Patisiran Safety and Tolerability Results from Phase 1 and 2 Studies Generally well tolerated in human volunteers (n=17) with single dose in Phase 11 No SAEs, no discontinuations due to study drug All AEs associated with drug administration mild or moderate in severity » Moderate infusion reacti
Slide 13: 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 14: Phase 3 Trial of Patisiran in FAP
Phase 3 Trial of Patisiran in FAP Study Ongoing Randomized, double-blind, placebo-controlled, global study 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) ~15 Patients 5 mg/kg dose (qd x5 load, qw x5 maintenance) Primary Objective Assess safety and tolerability Secondary Objective Obt
Slide 18: Patisiran and ALN-TTRsc Commercial Opportunity
Patisiran and ALN-TTRsc Commercial Opportunity Promising transformative approach for progressive, fatal disease Orphan disease with significant unmet need Breakthrough, disease-modifying treatment approach » >80% Knockdown of disease-causing TTR protein » Aim to halt disease progression, and pos
Slide 19: 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 20: 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 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 Dose-escalation Study in Two Parts Part 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 (N=~24) hemophilia A or B (N=up to 18) Primary Objective Prima
Slide 24: ALN-AT3 Commercial Opportunity
ALN-AT3 Commercial Opportunity New therapeutic approach in hemophilia and rare bleeding disorders Differentiated product with SC dosing that could change disease management by re-balancing coagulation system Hemophilia A and B represent >$9B market1 » Premium pricing established Potential fast
Slide 25: 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 26: 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 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: 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 29: Additional Programs (I)
Alnylam 5x15 TM Additional Programs (I) 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 N
Slide 30: Additional Programs (II)
TM Alnylam 5x15 Additional Programs (II) Hypercholesterolemia ALN-PCSsc Elevated LDL-C validated risk Targets PCSK9 factor Efficacy in multiple pre-clinical animal >500,000 Patients with severe models hypercholesterolemia DC selected; IND late ’14 / early ’15 Multiple genetically defined
Slide 31: 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, plasma ALA/PBG 3. Definable path to approval and market Establi
Slide 32: Financials and Goals
Financials and Goals ay DLAlnylam.
Slide 33: Financial Summary
Financial Summary 2013 Q4 Financial Results Cash ~$350.5M GAAP Revenues ~$10.8M » Takeda, Monsanto, The Medicines Company, others GAAP Operating Expenses ~$40.4M Shares Outstanding ~63.7M 2014 Guidance Year-end cash >$825M » >$1B pro forma balance sheet post-Genzyme alliance 33
Slide 34: 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 Phase 3 FAC TTR-FAC D D Phase 3 Human POC ALN-AT3 Phase 1 Pha
Slide 35: 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 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 Phase 1 data Hemophilia and RB
Slide 36: 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 37: Thank You
Thank You www.alnylam.com
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