Welcome to R&D Day! Christine Lindenboom VP, Investor Relations & Corporate Communications

Transcription

1 Welcome to R&D Day! Christine Lindenboom VP, Investor Relations & Corporate Communications 1

2 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 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 our ability to discover and develop novel drug candidates and delivery approaches, successfully demonstrate the efficacy and safety of our drug candidates, obtain, maintain and protect intellectual property, enforce our patents and defend our patent portfolio, obtain regulatory approval for products, establish and maintain business alliances; our dependence on third parties for access to intellectual property; and the outcome of litigation, as well as those risks more fully discussed in our most recent quarterly report on Form 10-Q under the caption Risk Factors. If one or more of these factors materialize, or if any underlying assumptions prove incorrect, our actual results, performance or achievements may vary materially from any future results, performance or achievements expressed or implied by these forward-looking statements. All forward-looking statements speak only as of the date of this presentation and, except as required by law, we undertake no obligation to update such statements. 2

3 R&D Day 2015 December 10, Agenda and Speakers Time Topic Presenter 7:15 8:00am Breakfast 8:00 8:05 Welcome & Introduction Christine Lindenboom 8:05 8:20 Path to Alnylam 2020 John Maraganore 8:20 8:40 Pipeline Overview & Updates from ATTR and ALN-PCSsc Akshay Vaishnaw Fitusiran (ALN-AT3) 8:40 8:55 Hemophilia Disease Overview Guy Young 8:55 9:20 Fitusiran for Hemophilia and Rare Bleeding Disorders Benny Sorensen 9:20 9:30 Q&A session Barry Greene 9:30 9:40 10 minute break ALN-AS1 9:40 9:55 Acute Hepatic Porphyrias Overview Robert Desnick 9:55 10:20 ALN-AS1 for Acute Hepatic Porphyrias Rachel Meyers 10:20 10:30 Q&A session Barry Greene ALN-CC5 10:30 10:45 Paroxysmal Nocturnal Hemoglobinuria Overview Anita Hill 10:45 11:10 ALN-CC5 for Complement-Mediated Diseases Pushkal Garg 11:10 11:20 Q&A session Barry Greene 11:20 11:30 Looking Forward John Maraganore 3

4 Path to Alnylam 2020 R&D Day 2015 John Maraganore, Ph.D., Chief Executive Officer 1

5 What we re about: RNAi Therapeutics A New Class of Innovative Medicines 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 for innovative medicines Clinically validated platform Human POC in multiple programs Papers in NEJM and Lancet 2

6 Where we were: 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 greatly exceed 2011 guidance 8 in Clinic 2 in Phase with Human POCs Product characteristics Genetically defined target/disease Existing Alnylam delivery platform Phase 1 proof of concept Clear and rapid development Significant commercial opportunity 3

7 Where we re going 4

8 5

9 6 >10 Clinical Read-outs in 2016

10 7 >5 Programs in Phase 3 in 2017

11 8 1 st Phase 3 data read out in 2017

12 9 How do we get there?

13 #1: Capital Financial Resources to Drive Pipeline Forward Strong Cash Position Q3 15 cash ~$1.34B Year-end cash guidance >$1.2B Alnylam-Genzyme Genetic Medicine Alliance Valued at well over $1B Equity R&D funding Milestones Royalties CAMBRIDGE, MA 10

14 #2: Reproducible and Modular Platform Risk-Mitigating Development Strategy Applied Across Programs 1 Genetically validated, liverexpressed target gene Liver-expressed targets involved in disease with high unmet need and validated through human genetics Delivery with GalNAc conjugate platform 2 Biomarker for POC in Phase 1 Blood- or urine-based biomarkers with strong disease correlation Establish dose/regimen for latestage development 3 Definable path to approval and market Clinical development plans with focused trial size and established endpoints Definable value for payers 11

15 #2: Reproducible and Modular Platform Rapid Path from Idea to Human POC with 100% Success to Date IDEA DEVELOPMENT CANDIDATE CTA/IND HUMAN POC 6 months months 6-9 months Success Rate at each stage to date: 100% 100% 100% 12

16 % Men KD in human % Mean KD #2: Reproducible and Modular Platform Fundamentally New Approach to Drug Development Preclinical POC Excellent Translation Human POC Select Dose/Regimen Start of Phase 3 Increased POS due to Genetically Validated Targets Phase 3 Data % Mean KD in NHP Months 13

17 #3: Competitive and Differentiated Profiles Robust Human Experience to Date* Number of Programs 7 Number of Clinical Studies 16 Total Patients or Volunteers Dosed >300 Longest Duration of Exposure >24 months Total sirna Doses Administered >4,500 *Numbers are approximate as many studies are ongoing 14

18 Mean (SEM) % C5 Knockdown Mean (SEM) % ALA Reduction Mean (SEM) % AT Lowering Mean (SEM) PCSK9 Knockdown #3: Competitive and Differentiated Profiles Potent and Durable Knockdown of Target Proteins Fitusiran 225 mcg/kg 450 mg/kg 900 mcg/kg 1800 mcg/kg ALN-PCSsc Placebo 25 mg 100 mg 300 mg 500 mg 800 mg Time (Days) Time (Months) ALN-CC ALN-AS1 Placebo mg/kg 0.1 mg/kg 0.35 mg/kg 1.0 mg/kg mg 200 mg 400 mg 600 mg 900 mg Placebo Time (Days) Time (Days) 15

19 #3: Competitive and Differentiated Profiles RNAi vs. Monoclonal Antibody (MAb) MAbs Transiently block protein in stoichiometric process, consumed by ongoing protein synthesis Saw-tooth effect 26 doses/year Protein Synthesis GalNAc mrna Nucleus RNAi sirna durably blocks protein synthesis in catalytic process Clamped effect 2 doses/year 16

20 #3: Competitive and Differentiated Profiles RNAi vs. Monoclonal Antibody (MAb) Potential resurgence of disease symptoms MAbs Transiently block protein in stoichiometric process, consumed by ongoing protein synthesis Saw-tooth effect 26 doses/year Protein Synthesis GalNAc mrna Nucleus RNAi sirna durably blocks protein synthesis in catalytic process Sustained suppression of disease symptoms Clamped effect 2 doses/year 17

21 #3: Competitive and Differentiated Profiles ESC-GalNAc sirna vs. ASO Dosing Gen 2.0/2.5 ASO & 1st Gen STC-GalNAc sirna GalNAc-ASO aka LICA 2nd Gen ESC- GalNAc sirna 52 DOSES PER YEAR 12 DOSES PER YEAR 2 DOSES PER YEAR 18

22 #4 Large Number of Opportunities Liver Targets across 3 Strategic Therapeutic Areas (STArs) Genetic Medicines Genetically validated liver targets for rare orphan diseases High unmet needs in focused markets SC dosing Alnylam direct commercial in NA and EU Genzyme alliance for ROW commercial Through end-2019 Cardio-Metabolic Disease Genetically validated liver targets for dyslipidemia, NASH, type 2 diabetes, and hypertension Development path in genetically defined, high unmet need subpopulations o Access to larger populations thereafter Emerging genetics qm, qq, or potentially bi-annual SC dosing Partnership opportunities Hepatic Infectious Disease Liver pathogen and/or host targets Sub-acute duration of treatment (~12 mo) Multiple sirnas possible, if needed Defined opportunities with very large markets qm or qq SC dosing Partnership opportunities 19