Second Quarter 2017 Financial Results August 9, 2017 1 Agenda - PowerPoint PPT Presentation

Colin Living with Porphyria Second Quarter 2017 Financial Results August 9, 2017 1

Agenda Welcome • Christine Regan Lindenboom Vice President, Investor Relations & Corporate Communications Q2 2017 Overview • John Maraganore, Ph.D. Chief Executive Officer Alnylam Clinical Pipeline • Akshay Vaishnaw, M.D., Ph.D. Executive Vice President of R&D Financial Results • Manmeet Soni Chief Financial Officer 2017 Goals Update • Barry Greene President Q&A Session 2

Alnylam Forward Looking Statements & Non-GAAP Financial Measures 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 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 and successfully demonstrate the efficacy and safety of our product candidates; pre-clinical and clinical results for our product candidates; actions or advice of regulatory agencies; delays, interruptions or failures in the manufacture and supply of our product candidates; our ability to obtain, maintain and protect intellectual property, enforce our intellectual property rights and defend our patent portfolio; our ability to obtain and maintain regulatory approval, pricing and reimbursement for products; our progress in establishing a commercial and ex- United States infrastructure; competition from others using similar technology and developing products for similar uses; our ability to manage our growth and operating expenses, obtain additional funding to support our business activities and establish and maintain business alliances; the outcome of litigation; and the risk of government investigations; 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. This presentation contains non-GAAP financial measures, including net loss adjusted to exclude certain non-cash expenses. These measures are not in accordance with, or an alternative to, accounting principles generally accepted in the U.S. (GAAP), and may be different from non- GAAP financial measures used by other companies. The item included in GAAP presentations but excluded for purposes of determining non- GAAP financial measures for the periods presented in this presentation is stock-based compensation expense. The company believes the presentation of non-GAAP net loss provides useful information to management and investors regarding the company’s financial condition and results of operations. When GAAP financial measures are viewed in conjunction with non-GAAP financial measures, investors are provided with a more meaningful understanding of the company’s ongoing operating performance. In addition, non -GAAP net loss is among those indicators the company uses as a basis for evaluating performance, allocating resources and planning and forecasting future periods. Non-GAAP financial measures are not intended to be considered in isolation or as a substitute for GAAP financial measures. A reconciliation between GAAP and non-GAAP net loss is provided later in this presentation. 3

John Maraganore, Ph.D. Chief Executive Officer Q2 2017 Overview 4

Strategic Context for Q2 2017 Earnings Call APOLLO Phase 3 topline results expected in mid-2017 • If positive, plan to file NDA by year-end; MAA shortly thereafter Building world-class team and capabilities in preparation for potential transition to commercial stage • Includes Quality, Compliance, Medical Affairs, Manufacturing, and Commercial teams • Buildup in U.S., Canada and Western Europe, and then Global Initiated ATLAS Phase 3 for fitusiran in hemophilia and expect to initiate two additional Phase 3 studies by YE • ATLAS Phase 3 program for fitusiran, an investigational RNAi therapeutic for the treatment of hemophilia, initiated in July • Givosiran, an investigational RNAi therapeutic for the treatment of acute hepatic porphyrias, in late 2017 • In collaboration with The Medicines Company, inclisiran, an investigational RNAi therapeutic for the treatment of hypercholesterolemia, in late 2017 5

Akshay Vaishnaw, M.D., Ph.D., Executive Vice President of R&D Alnylam Clinical Pipeline 6

Alnylam ATTR Amyloidosis Portfolio Committed to Continued Innovation for Patients Patisiran ALN-TTRsc02 • IV administration • ESC “second generation” chemistry • Phase 2 completed • Anticipate quarterly SC dose • Phase 3 trial regimen ongoing; fully enrolled with top- • Phase 1 ongoing; initial positive line results expected in mid- 2017 data presented December 2016 • APOLLO-OLE study ongoing 7

Patisiran Phase 2 OLE Final Study Results Change in mNIS+7 at 24 Months 29.6 20 out of 27* patients (74%) with no change or an improvement in 30 30 (3.1) mNIS+7 at month 24 compared to baseline 25.8 (9.4) 25 Mean (SEM) Δ mNIS+7 from baseline at 24 mos~ 25 20 20 Δ mNIS+7 from baseline to Month 24 15 15 9.2 10 (2.7) 10 5 Patisiran 5 Ph 2 OLE ^ (N=26) 0 0 // // (nonlinear; N=283) 1# Placebo (N=66) Diflunisal (N=64) Natural History -5 -5 -7.0 -10 -10 Diflunisal (2.0) Ph 3 Study 2+ -15 -15 -20 -20 -25 -25 Mean Δ mNIS+7 Across -30 -30 hATTR Amyloidosis Studies Individual Δ mNIS+7 at Month 24 (n=26) at 24 mos ~ -35 -35 Adams et al. , AAN, April 2017; SEM: Standard Error of the Mean; *One patient discontinued prior to the Month 24 assessment and is included in the denominator ~Assessments drawn from studies in patients with similar baseline neurologic impairment and not based on head-to-head studies #Predicted progression of median NIS value from Gompertz curve fit 1 +Linear interpolation from 2-year NIS progression measurement in longitudinal analysis set ^Patisiran results similar in patients with/without concurrent TTR stabilizer therapy; mNIS+7 using full mNIS+7 set; partial imputation was used to recover mNIS+7 data points where components were missing at one or more replicate measurements (per patient/visit) 8 1. Adams D et al . Neurology. 2015;85;675-682. 2. Berk JL et al . JAMA. 2013;310:2658-67.

Patisiran Phase 2 OLE Final Study Results TTR Amyloid Content in Skin: Lower Limb • Blinded analysis of tandem skin punch biopsies performed at central lab; statistical significance testing performed post-hoc • Dermal amyloid content in both distal thigh and distal leg decreased over time relative to baseline ◦ Statistically significant decrease in absolute change for distal thigh at 6, 18 and 24 months and at all time points for distal leg Distal thigh dermal amyloid content ‡ in Patient 050-0003 Mean Absolute Change from Baseline Median Relative Change from Baseline in Dermal Amyloid Content in Dermal Amyloid Content 12 months 18 months 24 months 6 months Mean Absolute Change from Baseline in 0 Median Relative Percent Distal Thigh N Change (IQR) Dermal Amyloid Content, % 6 months 22 -52.5 (-75.7, 0) 12 months † 19 -61.8 (-87.5, 0) -3.81* -5 -4.27 -4.58* N=20 18 months 20 -78.2 (-89.7, -8.3) N=20 N=22 24 months † 19 -23.8 (-78.3, 0) -6.38* Baseline -7.23* N=19 -8.01* N=22 Median Relative Percent N=20 -10 Distal Leg N Change (IQR) -9.48* N=18 -10.71* 6 months 22 -48.5 (-74.3, 0) N=19 12 months 18 -64.6 (-85.8, 0) Distal Thigh (Baseline Amyloid content (n=24): 10.9%) 18 months † 18 -67.5 (-91.3, -10) -15 Distal Leg 24 months † 18 -40.4 (-78.3, -21.6) (Baseline Amyloid content (N=24): 15.8%) * P<0.05 IQR, Interquartile Range; † 1 patient excluded due to baseline value of 0 and a non-zero post-baseline value 24months ‡ Red: Amyloid by Congo red staining 9 Adams et al. , AAN, April 2017