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

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Colin

Living with Porphyria

Second Quarter 2017 Financial Results

August 9, 2017

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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

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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;

• ur 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

• utcome 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.

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Q2 2017 Overview

John Maraganore, Ph.D. Chief Executive Officer

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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

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Alnylam Clinical Pipeline

Akshay Vaishnaw, M.D., Ph.D., Executive Vice President of R&D

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Alnylam ATTR Amyloidosis Portfolio

Committed to Continued Innovation for Patients Patisiran ALN-TTRsc02

• IV administration
• Phase 2 completed
• Phase 3 trial
• ngoing; fully enrolled with top-

line results expected in mid- 2017

• APOLLO-OLE study ongoing
• ESC “second generation”

chemistry

• Anticipate quarterly SC dose

regimen

• Phase 1 ongoing; initial positive

data presented December 2016

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ΔmNIS+7 from baseline to Month 24

• 35
• 30
• 25
• 20
• 15
• 10
• 5

5 10 15 20 25 30

Mean (SEM) ΔmNIS+7 from baseline at 24 mos~

• 35
• 30
• 25
• 20
• 15
• 10
• 5

5 10 15

Natural History (nonlinear; N=283)1#

Diflunisal Ph 3 Study2+

//

Placebo (N=66) Diflunisal (N=64)

//

Mean ΔmNIS+7 Across hATTR Amyloidosis Studies at 24 mos~

25.8 (9.4) 29.6 (3.1) 9.2 (2.7)

• 7.0

(2.0)

20 25 30

Patisiran Ph 2 OLE^ (N=26)

20 out of 27* patients (74%) with no change or an improvement in mNIS+7 at month 24 compared to baseline

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 fit1 +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)

• 1. Adams D et al. Neurology. 2015;85;675-682. 2. Berk JL et al. JAMA. 2013;310:2658-67.

Individual ΔmNIS+7 at Month 24 (n=26)

Patisiran Phase 2 OLE Final Study Results

Change in mNIS+7 at 24 Months

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• 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

Median Relative Change from Baseline in Dermal Amyloid Content Distal Thigh N Median Relative Percent Change (IQR)

6 months 22

• 52.5 (-75.7, 0)

12 months† 19

• 61.8 (-87.5, 0)

18 months 20

• 78.2 (-89.7, -8.3)

24 months† 19

• 23.8 (-78.3, 0)

Distal Leg N Median Relative Percent Change (IQR)

6 months 22

• 48.5 (-74.3, 0)

12 months 18

• 64.6 (-85.8, 0)

18 months† 18

• 67.5 (-91.3, -10)

24 months† 18

• 40.4 (-78.3, -21.6)

IQR, Interquartile Range; †1 patient excluded due to baseline value of 0 and a non-zero post-baseline value Baseline 24months

Distal thigh dermal amyloid content‡ in Patient 050-0003

• 4.58*
• 4.27
• 8.01*
• 3.81*
• 7.23*
• 9.48*
• 10.71*
• 6.38*
• 15
• 10
• 5

Distal Thigh

(Baseline Amyloid content (n=24): 10.9%)

Distal Leg

(Baseline Amyloid content (N=24): 15.8%)

* P<0.05

Mean Absolute Change from Baseline in Dermal Amyloid Content, %

6 months 12 months 18 months 24 months

N=22 N=18 N=20 N=20 N=19 N=20 N=19 N=22

Mean Absolute Change from Baseline in Dermal Amyloid Content

Patisiran Phase 2 OLE Final Study Results

TTR Amyloid Content in Skin: Lower Limb

Adams et al., AAN, April 2017

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• 7 patients (25.9%) with 10 reports of serious adverse

events (SAE); not related to study drug

• One discontinuation for gastroesophageal cancer at ~20

months; patient subsequently died

• One death due to myocardial infarction after patient completed

24 months of treatment

• One patient with 3 reports (distal femur fracture/proximal tibia

fracture/osteonecrosis/ligament rupture, dehydration/acute prerenal failure/urinary tract infection and thermal burn)

• One patient with 2 reports (ankle fracture/foot fracture/
• steonecrosis and ankle arthrodesis)
• One patient with venous thrombosis of the lower limb
• One patient with foot abscess and osteomyelitis
• One patient with pacemaker implantation due to amyloid

cardiomyopathy

• Majority of AEs were mild or moderate
• 5 patients (18.5%) had severe AEs not related to study drug
• Related AEs reported in ≥4 patients were infusion related

reaction (22.2%) and flushing (22.2%), all of which were mild

• No clinically significant changes in liver function tests,

renal function, or hematologic parameters, including platelets Adverse Events (AE) reported in ≥10% of patients

AE by Preferred Term Patisiran (N=27)

Flushing 7 (25.9%) Diarrhea 6 (22.2%) Infusion related reaction 6 (22.2%) Nasopharyngitis 6 (22.2%) Urinary tract infection 6 (22.2%) Vomiting 6 (22.2%) Wound 6 (22.2%) Nausea 5 (18.5%) Insomnia 4 (14.8%) Neuralgia 4 (14.8%) Pyrexia 4 (14.8%) Anemia 3 (11.1%) Bronchitis 3 (11.1%) Cataract 3 (11.1%) Infusion site extravasation 3 (11.1%) Edema peripheral 3 (11.1%) Macular degeneration 3 (11.1%) Musculoskeletal pain 3 (11.1%) Osteoporosis 3 (11.1%)

Patisiran Phase 2 OLE Final Study Results

Summary of Safety and Tolerability

Adams et al., AAN, April 2017

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ALN-TTRsc02 Opportunity

Potential for Best-in-Class Profile

Revusiran*/Inotersen ALN-TTRsc02

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DOSES PER YEAR

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DOSES PER YEAR ANTICIPATED

Ongoing Study in Normal Healthy Volunteers

Mean max TTR KD of 97.1 ± 0.5%; >80% TTR KD at Day 90 after single 50 mg dose**

Safety: Generally well tolerated in healthy volunteers (N=48)

• No SAEs or discontinuations due to AEs; all AEs mild or moderate
• 9 AEs in 5 subjects considered possibly related to treatment; all mild
• ISRs reported in 2 subjects – symptoms mild and transient
• No clinically significant changes in physical exams or lab parameters

(e.g., LFTs)

Most potent Alnylam RNAi therapeutic to date

*Alnylam discontinued development of revusiran in October 2016 **Data cut-off 26Oct2016; reported at Alnylam R&D Day in December 2016

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0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 Days since first dose 40 80 120 160 200 240 280 320 0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 Cohort Placebo (N=20) TTRSC02 (5mg) (N=6) TTRSC02 (25mg) (N=6) TTRSC02 (Optional; 25mg) (N=6) TTRSC02 (Subjects of Japanese descent; 25mg) (N=6) TTRSC02 (50mg) (N=6) TTRSC02 (Optional; 50mg) (N=6) TTRSC02 (Subjects of Japanese descent; 50mg) (N=6) TTRSC02 (100mg) (N=6) TTRSC02 (200mg) (N=6) TTRSC02 (300mg) (N=6)

ALN-TTRsc02 Phase 1 Preliminary Study Results

Single Ascending Dose Study in Healthy Volunteers

• No SAEs and no discontinuations due to AEs
• All AEs mild or moderate in severity
• 14 AEs in 8 subjects considered possibly related to treatment; majority mild
• Events included injection site erythema, injection site pain, injection site bruising, rhinorrhea,

pruritus, cough, nausea, fatigue, genital rash and abdominal pain

• No clinically significant changes in lab parameters, EKG or physical exam

As of data cutoff on 31May2017

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Fitusiran for Hemophilia

Potential to Restore Hemostasis in Hemophilia

Genetically validated, liver-expressed target gene Biomarker for POC in Phase 1 Definable path to approval and patient access

Established Endpoint Annualized Bleeding Rate (ABR)

AT FIX

FIXa FVIIa FVII FVIIIa FVa FV FX FXa Fibrinogen Fibrin

Thrombin

Prothrombin

Blood clot Hemophilia B Hemophilia A

AT

FIX FVIII Plasma Biomarkers AT Lowering, Thrombin Generation

20 40 60 80 100 120 140

AT Activity (%) Days

• 30

60 120 Peak Thrombin (nM)

20 40 60 80 100

Fitusiran Phase 1 results: Pasi et al., WFH, July 2016

Photo courtesy of Guy Young, M.D. Director, Hemostasis & Thrombosis Center at Children's Hospital Los Angeles and Professor of Pediatrics, USC Keck School of Medicine AT % Lowering Peak Thrombin

14 Safety in Phase 2 OLE: Generally well tolerated, median 11 months of dosing (N=33)

• 2 SAEs considered possibly related to study drug
• Asymptomatic ALT and AST elevation in patient with chronic HCV infection
• Seizure with confusion in patient with history of seizure disorder
• Majority of AEs mild or moderate in severity, unrelated to study drug
• Mild ISRs in 6 (18%) patients
• No thromboembolic events; no lab evidence for pathologic clot formation
• ALT increases >3x ULN observed in 11 (33%) patients
• All asymptomatic, with no concurrent elevations of bilirubin >2x ULN
• Reversible; all patients had medical history of HCV
• No instances of anti-drug antibody formation

Significant

increase in thrombin generation to

lower end of normal range Median estimated

ABR of

1

in all patients with up to 20 months treatment Median estimated

ABR of

in inhibitor patients Approximately

80%

AT lowering

Initial Evidence for Potential Restoration of Hemostasis in Severe Hemophilia A and B

DURABILITY

Monthly SC fixed dose regimen

*Clinical results as of Jun 15, 2017; Pasi et al., ISTH, July 2017 Alnylam, Sanofi Genzyme 50-50 US/Can/Western Europe; Sanofi Genzyme ROW

PLANNED NEXT STEPS

ATLAS Phase 3 results

in mid- to late 2019

Fitusiran Phase 2 OLE Study Results*

Ongoing Study in Hemophilia A & B Patients, Including Inhibitors

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Fitusiran ATLAS Phase 3 Program

Initiated in July 2017

• Adults and adolescents

with hemophilia A or B with inhibitors

• Currently manage bleeds

with on-demand bypassing agent therapy

• N~50

2:1 9 months fitusiran 9 months

• n-demand BPA

Primary Endpoints:

• ABR†

Secondary Endpoints:

• Spontaneous ABR
• Joint ABR
• QOL (Haem-A-QOL)

OR

• Adults and adolescents

with hemophilia A or B with

• r without inhibitors
• Currently manage bleeds

prophylactically

• N~100

7 months fitusiran 6 months PPX factor/BPA

• Adults and adolescents

with hemophilia A or B without inhibitors

• Currently manage bleeds

with on-demand (OD) factor replacement therapy

• N~100

2:1 Patients who complete the study may be eligible for fitusiran treatment in ATLAS-OLE study 9 months fitusiran 9 months

• n-demand factor

OR Primary Endpoints:

• ABR‡

Secondary Endpoints:

• Spontaneous ABR
• Joint ABR
• QOL (Haem-A-QOL)

Primary Endpoints:

• ABR in factor/BPA

and fitusiran period Secondary Endpoints:

• Spontaneous ABR
• Joint ABR
• QOL (Haem-A-QOL)

†ATLAS-INH powered to detect as little as a 60% reduction from control to fitusiran ‡ATLAS-A/B powered to detect as little as a 50% reduction from control to fitusiran

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Acute Hepatic Porphyrias

Disease Overview

Acute Hepatic Porphyrias (AHP)1,2

• Inborn errors of heme synthesis from liver enzyme

defects

• AIP (Acute Intermittent Porphyria) most common,

with a mutation in hydroxymethylbilane synthase (HMBS)

Disease Pathophysiology

• Induction of ALAS1 leads to accumulation of toxic

heme intermediates ALA/PBG that cause disease manifestations

Acute Attacks and Chronic Manifestations

• Autonomic Nervous System
• Severe abdominal pain, hypertension
• Central Nervous System
• Mental status changes, seizures
• Peripheral Nervous System
• Muscle weakness, paralysis

Treatment and Unmet Need

• Glucose and hemin used to treat acute attacks and

by some specialists to prevent attacks

• Unmet need for more efficacious, long acting, and

safer therapies to prevent attacks and improve chronic disease manifestations

Glycine Hydroxymethylbilane Uroporphyrinogen Coproporphyrinogen Protoporphyrinogen

Heme

δ- Aminolevulinic acid (ALA) Porphobilinogen (PBG) Protoporphyrin Succinyl CoA ALA Synthase 1 (ALAS1)

Fe 2+

Feedback inhibition

Disease triggers

HMBS

(PBGD)

Hereditary Coproporphyria (HCP) Variegate Porphyria (VP) Acute Intermittent Porphyria (AIP)

CPOX PPOX

ALAD Porphyria

ALAD FECH

1.Bonkovsky, et al. Am J Med. 2014;127(12):1233-41; 2.Elder, et al. JIMD. 2013;36(5):849-57.

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Givosiran: Investigational RNAi Therapeutic

Therapeutic Hypothesis

Reduction of Liver ALAS1 Protein to Lower ALA/PBG

ALAS1 protein Givosiran

Givosiran (ALN-AS1) results in knockdown of ALAS1 and lowers ALA/PBG production to prevent attacks and disease symptoms ALA/PBG induce porphyria symptoms

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73%

Mean Decrease in

Annualized Attack Rate** compared with placebo

73%

Mean Decrease in

Annualized Hemin Use

Initial evidence for further reductions in annualized attack rate with extended dosing in OLE

Up to

79%

lowering of ALA,

77%

lowering of PBG PLANNED NEXT STEPS

Start Phase 3

in late 2017

*Interim Phase 1 study results as of Apr 21, 2017; Sardh et al., ICPP, June 2017; ** Includes attacks treated in healthcare facility or with hemin Alnylam retains global rights to the givosiran program

Safety: Generally well tolerated (N=9)

• No drug-related SAEs and no discontinuations due to AEs
• As reported previously, one patient developed acute pancreatitis complicated

by pulmonary embolism resulting in death, considered unlikely related to study drug

• Majority of AEs mild-moderate in severity
• AEs possibly related include ISRs, hypersensitivity, myalgia, headache,

moderate renal impairment (in patient with history of same), and erythema

• No clinically significant changes in vital signs, EKG, or clin labs

DURABILITY

Monthly and possibly quarterly SC dose regimen

Initial Evidence for Clinical Activity in Recurrent Attack Porphyria Patients

Givosiran Interim Phase 1 Study Results*

Ongoing Randomized, Double-Blind, Placebo-Controlled Study in Recurrent Attack Porphyria Patients

FDA Breakthrough and EMA PRIME Designations

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41 10 4 5 10 15 20 25 30 35 40 45 Run-In Treatment OLE

Annualized Hemin Doses 27 9 5 5 10 15 20 25 30 Run-In Treatment OLE Annualized Attack Rate

Givosiran activity maintained, potential for further reductions in attack rate with extended dosing

Run-In Treatment OLE Mean Days on Study 90 169 111

Interim Givosiran Phase 1 (Part C, Cohorts 1-2 OLE) Study Results

Clinical Activity

Mean Annualized Attack Rate Cohorts 1 and 2

N=6 N=6 N=6 N=6 N=6 N=6

Mean Annualized Hemin Doses Cohorts 1 and 2

Data cut date of 21 Apr 2017

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Clinical Activity, Placebo

29 23 5 10 15 20 25 30 35 Run-In Placebo Treatment OLE

Mean Annualized Attack Rate Placebo

Annualized Attack Rate

N=2 N=2 N=2

Run-In Treatment OLE Mean Days on Study 77 169 31

Interim Givosiran Phase 1 (Part C, Cohorts 1-2 OLE) Study Results

Data cut date of 21 Apr 2017

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Interim Givosiran Phase 1 (Part C and OLE) Study Results

Safety and Tolerability

All Safety Data in database as of 5 May 2017

Part C (Cohorts 1-3)

• 3 patients had 4 SAEs (excluding porphyria attacks), none assessed as related to study drug
• 1 patient in Cohort 3 had fatal SAE of hemorrhagic pancreatitis, complicated by pulmonary embolism, as

previously reported. Assessed unlikely related due to presence of gallbladder sludge

• All randomized patients reported AEs
• Majority of AEs were mild to moderate; 25% patients had severe AEs, assessed as unrelated to study drug
• AEs in ≥3 patients: Abdominal pain, headache, nasopharyngitis, nausea, vomiting
• 4 patients had related AEs:

– Injection site reactions (mild and self-limiting), hypersensitivity, myalgia, headache, moderate renal impairment (in patient with history of moderate renal impairment) and erythema

• No other discontinuations due to AEs or other clinically significant changes in EKG, clinical

laboratory or physical examination

OLE (Cohorts 1-2)

• Overall safety experience in OLE is consistent with Phase 1 Study
• No SAEs (excluding porphyria attacks) or discontinuations due to AEs
• 4 patients reported AEs; Most assessed as mild or moderate in severity
• 2 patients experienced mild or moderate AEs that were considered related or possibly related to study drug

(epistaxis, hypertension and renal impairment, in same patient with history of moderate renal impairment as noted above)

• No clinically significant changes in EKG, clinical laboratory or physical examination reported

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Other Programs to Watch

Inclisiran for Hypercholesterolemia*

53%

mean LDL-C lowering at Day 180 after two quarterly doses1

ALN-CC5 for Complement-Mediated Diseases

Sustained control

• f disease hemolysis

with up to

67%

reduction in eculizumab dose in PNH patients2

ALN-HBV for Hepatitis B Virus (HBV) Infection ALN-GO1 for Primary Hyperoxaluria 1 (PH1)

Pre-clinical results:4

up to

3.6 log10

HBsAg reduction

Up to

8-fold

increase in plasma glycolate in healthy volunteers3

PLANNED NEXT STEPS FOR INCLISIRAN:

Start Phase 3 study

in late 2017

Safety (N=32):

• No SAEs, no discontinuations due to AEs
• All AEs mild or moderate, with exception
• f one subject with transient,

asymptomatic CPK elevation considered unrelated to study drug Safety (N=6):

• No SAEs, no discontinuations due to

AEs

• 1 AE of hemolysis in setting of URI;

moderate in severity and considered unrelated to study drug

• 1 AE of asymptomatic, transient grade 3

elevation of LFTs; considered possibly related Safety (N=501):

• No drug-related SAEs, no discontinuations

due to AEs

• Two patient deaths due to MI and stroke,

both unrelated to study drug

• No LFT elevations related to study drug
• Majority of AEs mild or moderate in severity

*The Medicines Company is leading and funding development of inclisiran from Phase 2

• nward and will commercialize the program, if successful

RECENT ACTIVITY FOR ALN-GO1:

First PH1 Patient Dosed

in March 2017

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Q2 2017 Financial Results

Manmeet Soni Chief Financial Officer

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Financial Summary and Guidance

2017 Q2 Financial Results

• Cash $1.25B
• Includes $355.2M of net proceeds from the May 2017 public offering
• Includes $21.4M of proceeds from Sanofi Genzyme’s purchase of common stock
• Includes $150.0M in restricted investments
• GAAP Revenues $15.9M
• Total GAAP Operating Expenses $136.4M
• Research and Development Expenses $90.6M
• General and Administrative Expenses $45.8M
• GAAP Net Loss $118.4M
• Non-GAAP Net Loss* $94.4M
• Shares Outstanding 91.7M

2017 Guidance

• Year-end cash >$1.0B
• Includes $150.0M in restricted investments

* Non-GAAP net loss excludes stock-based compensation expenses. See Appendix for a

reconciliation between GAAP and non-GAAP net loss.

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2017 Goals Update

Barry Greene President

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Transition to Potential Commercialization

Planned Rapid Launch Succession

Givosiran

~2020

Patisiran

~2018

Fitusiran

~2019

Building commercial capabilities to prepare for upcoming product launches

• Patisiran in US, Canada, and Western

Europe

• Fitusiran co-develop/co-commercialize

in US, Canada, and Western Europe

• Givosiran globally

Manufacturing build-out to ensure consistent drug supply underway

• Alewife facility fully operational and

ready for patisiran launch

• Norton drug substance facility

expected to be commercially

• perational in 2020

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2017*

Early Mid Late

PATISIRAN

(hATTR Amyloidosis)

Phase 2 OLE data APOLLO Phase 3 top-line APOLLO Phase 3 results NDA/MAA filing

FITUSIRAN

(Hemophilia and RBD)

Phase 2 OLE data ATLAS Phase 3 program start

GIVOSIRAN

(Acute Hepatic Porphyrias)

Phase 1, Part C data Phase 3 study start

INCLISIRAN**

(Hypercholesterolemia)

ORION-1 Phase 2 data ORION-2 HoFH study start ORION-3 Phase 2 OLE study start ASCVD Phase 3 study start

ADDITIONAL CLINICAL PROGRAMS

Continue to advance early/mid-stage pipeline; Present clinical data

*Early is Q1-Q2, Mid is Q2-Q3, and Late is Q3-Q4

Alnylam 2017 Pipeline Goals

**Based on The Medicines Company guidance as of January 2017

28

Q&A Session

Q2 2017 Financial Results

29

Thank You

30

Appendix

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Alnylam Pharmaceuticals, Inc. Reconciliation of GAAP Net Loss to Non-GAAP Net Loss (In thousands, except per share amounts)

2017 2016 2017 2016 GAAP net loss (118,420) $ (90,129) $ (225,710) $ (193,103) $ Adjustment: Stock-based compensation expenses 24,030 15,816 39,747 39,296 Non-GAAP net loss (94,390) $ (74,313) $ (185,963) $ (153,807) $ GAAP net loss per common share-basic and diluted (1.34) $ (1.05) $ (2.59) $ (2.26) $ Adjustment (as detailed above) 0.27 0.18 0.45 0.46 Non-GAAP net loss per common share-basic and diluted (1.07) $ (0.87) $ (2.14) $ (1.80) $ Three Months Ended June 30, Six Months Ended June 30,