Alnylam Pharmaceuticals, Inc. · NASDAQ:ALNY
Alnylam Pharmaceuticals — Cowen and Company 32nd Annual Health Care Conference (March 2012)
34 slides from Alnylam Pharmaceuticals's conference presentation, Mar 7, 2012
Slide 1: Cowen and Company 32nd Annual Health Care Conference
March 7, 2012 Cowen and Company 32 nd Annual Health Care Conference Exhibit 99.1
Slide 2: RNA Interference (RNAi): A New Class of Innovative Medicines
3 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
Slide 3: RNAi Delivery to Liver Solved
4 RNAi Delivery to Liver Solved I.V. and SubQ Platforms Enables advancement of innovative medicines to patients Potent, rapid, and durable target gene silencing with proprietary lipid nanoparticle (LNP) technology and i.v. dosing Advancement of conjugate platform for clinical translation and subQ do
Slide 4: RNAi Human Translation Achieved
5 RNAi Human Translation Achieved Multiple Alnylam Therapeutic Programs Human Safety and PK >500 Subjects/patients enrolled overall Systemic delivery in human trials » ~100 Patients dosed » >275 Doses administered » >18 Months of dosing RNAi therapeutics generally well tolerated Pharmacologically re
Slide 5: RNAi Therapeutics Profile
6 Day Post Dose % Target Knockdown RNAi Therapeutics Profile Single dose… …Durable and reversible …Durable and reversible (dosing q30-60 days) (dosing q30-60 days) Potent and rapid… Potent and rapid… Potential for Major Therapeutic Impact
Slide 6: Alnylam 5x15: Focused Product Development Pipeline
7 Alnylam 5x15 ™ Focused Product Development Pipeline for Innovative Medicines RNAi for genetically defined disease as core strategy Key products in clinical development through 20 15 Near term focus on TTR and APC programs Product characteristics Genetically defined target/disease Existing Alnylam
Slide 7: Alnylam 5x15: Focused Product Development Pipeline
8 Alnylam 5x15 ™ Focused Product Development Pipeline for Innovative Medicines RNAi for genetically defined disease as core strategy Key products in clinical development through 20 15 Near term focus on TTR and APC programs Product characteristics Genetically defined target/disease Existing Alnylam
Slide 8: Slide 8
Slide 9: TTR Target and ALN-TTR Program
10 ALN-TTR in clinical development Targets mutant and wild-type TTR Positive preliminary clinical results with TTR01 ALN-TTR02 CTA accepted ALN-TTRsc in R2D for 2012 IND TTR Target and ALN-TTR Program Mutant TTR is genetic cause of ATTR >100 Defined mutations; autosomal dominant Misfolds and forms a
Slide 10: ALN-TTR Therapeutic Efficacy
11 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 ALN-TTR01
Slide 11: ALN-TTR01 Phase I Study
12 ALN-TTR01 Phase I Study Study Design Randomized, placebo-controlled, single-blind, single-dose escalation study » 3:1 Randomization » 4 Patients/cohort » 7 Dose groups (0.01-1.0 mg/kg) 32 Patients with ATTR » Conducted in Portugal, Sweden, France and UK Primary Objective Evaluate safety and toler
Slide 12: gede
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Slide 13: ALN-TTR01 Phase I Study Results
14 ALN-TTR01 Phase I Study Results Robust RNAi in Patient at 1.0 mg/kg ALN-TTR01 Single 1.0 mg/kg dose TTR knockdown by 81% at nadir Similar reductions in RBP and vitamin A Rapid onset with >50% lowering at day 2 Nadir at ~day 7 Durable effect with ~50% lowering at day 28 TTR protein Vitamin A RBP D
Slide 14: ALN-TTR Program
15 ALN-TTR Program ALN-TTR02 >10-fold improved efficacy in animal models Uses proprietary 2 nd generation MC3 LNP formulation ~90% Knockdown at 0.3 mg/kg Potential for q30-q60 day dosing Oligo Ther Soc., Sep 2011
Slide 15: ALN-TTR02 Phase I Study
16 ALN-TTR02 Phase I Study Study Design Randomized, placebo-controlled, single-dose escalation study ~32 Healthy volunteer subjects » To be conducted in UK Primary Objective Safety and tolerability Secondary Objectives Characterize PK Assess preliminary PD activity and clinical activity » Serum TTR
Slide 16: TTR Knockdown and Clinical Outcomes
17 TTR Knockdown and Clinical Outcomes Rationale for Expected Benefit TTR knockdown is validated endpoint ~50% Knockdown in other systemic amyloidoses » Disease improvement or stabilization Elimination of mutant TTR following liver transplantation » Disease improvement or stabilization Stabilization
Slide 17: ALN-TTR Commercial Opportunity
18 ALN-TTR Commercial Opportunity ALN-TTR product profile and ATTR opportunity Orphan disease with significant unmet need Breakthrough potential of ALN-TTR » >80% TTR knockdown with single dose; rapid and durable » Achieve disease regression » 6 – 12 doses per year » Fastest initial opportunity with
Slide 18: Slide 18
Slide 19: Protein C Target and ALN-APC Program
20 ALN-APC in R2D Efficacy in pre-clinical animal models IND Filing 2013 No Co-Inheritance With Co-Inheritance Protein C Target and ALN-APC Program Protein C (PC) is genetically defined target Activated Protein C (APC) drives key natural anticoagulant pathway » Inactivates factors Va and VIIIa » Att
Slide 20: APC Resistance and FV Leiden in Hemophilia
21 APC Resistance and FV Leiden in Hemophilia Improved Hemostasis in hemophilia (A or B) x FV Leiden mice Improved Thrombin Generation with FV Leiden in hemophilia A patient plasma van ‘t Veer et al., Blood; 90:3067-3072 (1997) 50:50 wt FV:FV Leiden 100% FV Leiden 100% wt FV Schlachterman et al., J
Slide 21: Protein C mRNA Silencing
Protein C mRNA Silencing (% Control Pre-dose) Control siRNA (0.3mg/kg) ALN-APC (0.3mg/kg) 4 8 2 Time (days) 16
Slide 22: Hemophilia Areas of Unmet Need
23 Hemophilia Areas of Unmet Need Acute (acute bleed, surgery) Chronic Managed with factor replacement therapy Potential for adjunctive therapy for improved outcomes Replacement factor therapy » “On demand” or “Prophylaxis” regimens Inconvenience (i.v. 3x/wk) major issue Potential for adjunctive the
Slide 23: Hemophilia Areas of Unmet Need
24 Hemophilia Areas of Unmet Need Acute (acute bleed, surgery) Chronic Managed with factor replacement therapy Potential for adjunctive therapy for improved outcomes Replacement factor therapy » “On demand” or “Prophylaxis” regimens Inconvenience (i.v. 3x/wk) major issue Potential for adjunctive the
Slide 24: ALN-APC Commercial Opportunity
25 ALN-APC Commercial Opportunity ALN-APC product profile and hemophilia opportunity Hemophilia A and B represent $6+ Billion market » Tremendous potential for differentiated products that fundamentally change disease management Prophylaxis with replacement factors is standard of care – unmet need s
Slide 25: LAinylany.
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Slide 26: ALN-PCS Phase I Study
27 ALN-PCS Phase I Study Study Design Randomized, placebo-controlled, single-dose escalation study ~32 Healthy volunteer subjects with elevated baseline LDL-C (>116mg/dL) » Conducted in UK » 3:1 Randomization » 4 Patients/cohort » 5 Current dose groups (0.015-0.25 mg/kg) Primary Objective Safety and
Slide 27: ALN-PCS Phase I Study Results
28 ALN-PCS Phase I Study Results RNAi efficacy toward validated clinical end point Rapid, dose-dependent, and durable silencing of PCSK9 of up to 66% with mean lowering of 60% at current highest dose (p<0.001) Major reductions in LDL-C of over 50% with mean lowering of 39% at current highest dose at
Slide 28: Alnylam 5x15 Programs: Definable Clinical Paths with Phase I POC
29 Program Indication: Unmet Need Phase I Serum Biomarkers Early Development Advanced Development Alnylam 5x15 ™ Programs Definable Clinical Paths with Phase I POC ALN-TTR ATTR : Significant morbidity and mortality -60 yrs of age with neuropathy and cardiomyopathy • TTR • Vitamin A • Retinol binding
Slide 29: Alnylam Development Pipeline
30 Discovery Development Phase I Phase II Phase III TTR-Mediated Amyloidosis Hemophilia Severe Hypercholesterolemia Refractory Anemia Hemoglobinopathy Respiratory Syncytial Virus Liver Cancers Huntington’s Disease Alnylam Development Pipeline Partner Programs Alnylam 5x15 Programs ALN-RSV01 ALN-TTR0
Slide 30: Additional Alnylam Opportunities
31 Additional Alnylam Opportunities Focused on microRNA therapeutics Co-Founded by Alnylam and Isis Alnylam 45% equity ownership Partnerships with GSK and sanofi Lead programs Anti-miR122 for HCV infection Human POC established Anti-miR21 for cancer Anti-miR33 for hypercholesterolemia
Slide 31: Financials and Goals
32 Financials and Goals * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * *
Slide 32: Financial Summary
33 Financial Summary 2011 Q4 Financial Results Cash ~$261M » ~$6.11 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 2012 Guidance Year-end Cash >$250M
Slide 33: Alnylam Goals
34 Alnylam Goals Pipeline Goals 2012-2013 Additional Corporate Goals 2012 Additional partnerships Year-end Cash >$250M
Slide 34: Thank You
35 Thank You www.alnylam.com
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