Alnylam Pharmaceuticals, Inc. · NASDAQ:ALNY

Alnylam Pharmaceuticals — Investor Presentation (September 2011)

29 slides from Alnylam Pharmaceuticals's investor presentation, September 2011

  1. Slide 1: Corporate Overview

    Corporate Overview September 2011

  2. Slide 2: Alnylam Forward Looking Statements

    Alnylam Forward Looking Statements This presentation contains forward-looking statements. There are a number of important factors that could cause actual results to differ materially from the results anticipated by these forward-looking statements. These important factors include those that we discu

  3. Slide 3: RNA Interference (RNAi)

    RNA Interference (RNAi) A New Class of Innovative Medicines RNAi Therapeutics  Harness natural pathway » Catalytic mechanism » Mediated by small interfering RNAs or “siRNAs”  Treat disease with therapeutic gene silencing » Any gene in genome – Creates unique opportunities for innovative medicines

  4. Slide 4: RNAi Therapeutics: The Time is Now: Reasons

    RNAi Therapeutics The Time is Now: 3 Reasons 1. Delivery breakthroughs 2. Growing human experience: safety and predictable PK enable clinical translation  >500 Subjects/patients enrolled overall  Systemic delivery in human trials 1.2 » > 60 Patients dosed Pre-Clinical Animal Studies » >200 Doses a

  5. Slide 5: Alnylam 5x15

    Alnylam 5x15 TM Focused Product Development Pipeline for Innovative Medicines RNAi for genetically defined disease ALN-HTT as core strategy  5 Products by 2015 in advanced clinical development  Product characteristics ALN-VSP Core Programs  Genetically defined target/disease 1. ALN-TTR 2. ALN-PCS

  6. Slide 6: Alnylam Development Pipeline

    Alnylam Development Pipeline Discovery Development Phase I Phase II Phase III ALN-TTR01 TTR-Mediated Amyloidosis ALN-TTR02 Severe Hypercholesterolemia ALN-PCS Hemophilia ALN-APC Refractory Anemia ALN-HPN Program 5 (TBA) Respiratory ALN-RSV01 Syncytial Virus Liver Cancers ALN-VSP Huntington’s ALN-HTT

  7. Slide 7: TTR-Mediated Amyloidosis (ATTR) Program: Unmet Need and Product Opportunity

    Transthyretin (TTR)-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 » Two predominant forms – Familial amyloidotic polyneuropathy (FAP) –

  8. Slide 8: TTR Target and ALN-TTR Program

    TTR Target and ALN-TTR Program Phe33Cys Ala45Asp Ser77Phe Leu12Pro Phe33Ile Ala45Ser Ser77Thy Phe33Leu Leu111Met Ala45Thr Gly53Glu Phe33Val Ala97Gly Glu61Lys Ala120Ser Pro24Ser Glu51Gly Ala97Ser Asp38Ala Ile73Val Ile68Leu Ala91Ser Ile107Val Thr118Met Val20Ile Glu42Asp Leu55Arg Val28Met Gly6Ser Glu42

  9. Slide 9: ALN-TTR Therapeutic Efficacy

    ALN-TTR Therapeutic Efficacy V30M TTR Transgenic Model ALN-TTR01 treatment results in TTR amyloid regression  Treatment paradigm in animals with existing amyloid plaques  >90% Regression of existing V30M hTTR deposits in peripheral tissues  Similar animal model data in prevention paradigm 70 Cont

  10. Slide 10: ALN-TTR01 Phase I Study

    ALN-TTR01 Phase I Study Study Design  Randomized, placebo-controlled, single-dose escalation study  ~36 Patients with ATTR » Conducted in Portugal, Sweden, UK and France  Primary objective » Safety and tolerability  Secondary objectives » Characterize pharmacokinetics » Assess preliminary pharma

  11. Slide 11: 2nd Generation ALN-TTR Program ALN-TTR02

    2nd Generation ALN-TTR Program 120 ALN-TTR02 Serum TTR Concentration (% Control Pre-dose) Control 100 ALN-TTR02 shows >10-fold improved in vivo efficacy in animal 80 models  ALN-TTR02 uses 2nd generation 60 MC3 LNP formulation ALN-TTR01  Single i.v. infusion; Serum TTR (1.0 mg/kg) 40 levels post-d

  12. Slide 12: Severe Hypercholesterolemia Program

    Severe Hypercholesterolemia Program Unmet Need and Product Opportunity RNAi to treat severe hypercholesterolemia  Elevated LDLc (“bad” cholesterol) is validated risk factor for coronary artery disease and MI » Current target level <70 mg/dL  Significant unmet medical need » >500,000 Patients with

  13. Slide 13: PCSK9 Target and ALN-PCS Program

    PCSK9 Target and ALN-PCS Program PCSK9 function well defined PCSK9 Peripheral  PCSK9 (proprotein convertase subtilisin/kexin type 9) cells expressed predominantly in liver  Both intracellular and extracellular PCSK9 regulate LDL LDL receptor (LDLr) levels on hepatocytes Liver » Increased PCSK9 dec

  14. Slide 14: ALN-PCS Pre-Clinical Efficacy

    ALN-PCS Pre-Clinical Efficacy Phenocopies Human Genetics ALN-PCS demonstrates potent efficacy after single dose  Rapid and dose-dependent reduction in PCSK9 protein  PCSK9 silencing results in >50% reduction in LDLc  Durable efficacy lasting >30 days  No decrease in HDL levels 800 100 control (1

  15. Slide 15: ALN-PCS Phase I Study

    ALN-PCS Phase I Study Study Design  Randomized, placebo-controlled, single-dose escalation study  ~32 healthy volunteer subjects with elevated baseline LDLc (>116mg/dL) » Conducted in UK  Primary objective » Safety and tolerability  Secondary objectives » Characterization of pharmacokinetics » A

  16. Slide 16: Hemophilia Program

    Hemophilia Program Unmet Need and Product Opportunity RNAi to treat hemophilia  Hemophilias are recessive X-linked monogenic bleeding disorders » Hemophilia A defined by loss of function mutations in Factor VIII – >40,000 Patients in EU/US » Hemophilia B defined by loss of function mutations in Fac

  17. Slide 17: Protein C Target and ALN-APC Program

    Protein C Target and ALN-APC Program Protein C (PC) is genetically defined target Intrinsic system Extrinsic system  Activated Protein C (APC) defines key Hemophilia B FVIIa FVII FX natural anticoagulant pathway FIX FIXa » Inactivates factors Va and VIIIa Hemophilia A » Attenuates thrombin generati

  18. Slide 18: ALN-APC Pre-clinical Efficacy

    ALN-APC Pre-clinical Efficacy Robust and Durable Silencing After Single Dose ALN-APC demonstrates potent efficacy after single dose  Dose-dependent silencing with ED50 ~0.02 mg/kg  Rapid and durable efficacy after single injection  Significant reduction in Protein C plasma levels Dose-Dependent S

  19. Slide 19: Refractory Anemia Program

    Refractory Anemia Program Unmet Need and Product Opportunity RNAi to treat refractory anemia  Anemia of chronic disease (ACD) across multiple populations » End-stage renal disease (ESRD) » Cancer » Chronic inflammatory disorders  Significant unmet need; e.g., ESRD » Resistant to high doses of EPO

  20. Slide 20: Hepcidin Pathway and ALN-HPN Program

    Hepcidin Pathway and ALN-HPN Program Liver Hepcidin pathway is genetically defined IL6 Infection, LPS Elevated Hepcidin  Hepcidin is central regulator of iron High serum iron hepcidin Other (e.g., uremia) levels homeostasis » Down-regulates ferroportin ─ Reduces iron uptake by enterocytes ─ Reduces

  21. Slide 21: Alnylam 5x15 Programs: Definable Clinical Paths with Phase I POC

    Alnylam 5x15 Programs TM Definable Clinical Paths with Phase I POC Unmet Phase I Serum Early Advanced Need Biomarkers Development Development ALN-TTR Significant morbidity • TTR Dose/regimen for FAP: Improvement and mortality 45-60 yrs • Vitamin A >50% TTR in neuropathy of age with neuropathy • Reti

  22. Slide 22: Partner Programs

    Partner Programs Respiratory Syncytial Virus Liver Cancer Huntington’s Disease  Significant unmet medical need  Prevalent solid tumor and common  Significant inherited » >125,000 Pediatric hosp./yr in US site of metastatic disease neurodegenerative disease » ~700,000/yr Incidence of HCC » Caused

  23. Slide 23: RNAi Technologies and New Ventures

    RNAi Technologies and New Ventures Bioprocessing/ Genomics Biologics RNAi RNAi pathway cartoon Stem Cells microRNA Therapeutics Other Non-Coding RNAs (e.g., RNAa) Vaccines 23

  24. Slide 24: Regulus Therapeutics

    Regulus Therapeutics Leading microRNA Therapeutics Company  Co-Founded by Alnylam and Isis  Focused on microRNA therapeutics  Key IP for microRNA therapeutics field  Lead programs  Anti-miR122 for HCV infection  Anti-miR21 for heart failure/fibrosis/cancer  Anti-miR33 for hypercholesterolemia

  25. Slide 25: Alnylam Biotherapeutics

    Alnylam Biotherapeutics Enabling Innovations in the Manufacture of Biologics  Transformative for biologics manufacturing  RNAi enables production of proteins and Mabs » Powerful and established cell biology tool applied at scale – Transient genetic manipulation – Target multiple pathways specifica

  26. Slide 26: Financials and Goals

    Financials and Goals a MACEUTICALS

  27. Slide 27: Financial Summary

    Financial Summary 2011 Q2 Financial Results  Cash ~$316M » ~$7.50 per share  GAAP Revenues ~$21M » Roche, Takeda, Cubist, and other licenses  GAAP Operating Expenses ~$34M » Includes non-cash stock-based compensation charges of ~$4M  Shares Outstanding ~43M 2011 Guidance  Year-end Cash >$250M 2

  28. Slide 28: Alnylam Goals

    Alnylam Goals Pipeline Goals 2011-2012 Phase I Phase II Phase II R2D IND Human POC Start Data ALN-TTR01   Q4 ’11 2012 ALN-TTR02  H2 ’11 H1 ’12 Alnylam 5x15 Programs ALN-PCS  H1 ’11  H2 ’11 ALN-HPN  2012 ALN-APC Q3 ’11 2013 Program 5 Q4 ’11 ALN-RSV01     2012 Programs Partner ALN-VSP   

  29. Slide 29: Thank You

    Thank You www.Alnylam.com 29

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