1© 2018 Alnylam Pharmaceuticals, Inc.

April 2018

Corporate Overview

2

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 report on Form 10-K 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.

Alnylam Forward Looking Statements

3

Clinically Proven Approach with Transformational Potential

RNAi Therapeutics: New Class of Innovative Medicines

Potent and durable mechanism of action

Product engine for sustainable pipeline

Nobel Prize-winning science

Silence any gene in genome

Now entering commercial stages

4

Alnylam Clinical Development Pipeline

1POC, proof of concept – defined as having demonstrated target gene knockdown and/or additional evidence of activity in clinical studies2Includes marketing application submissions

HUMAN

POC1

BREAKTHROUGH

DESIGNATIONEARLY STAGE

(IND or CTA Filed-Phase 2)

LATE STAGE

(Phase 2-Phase 3)

REGISTRATION/

COMMERCIAL2

COMMERCIAL

RIGHTS

PatisiranHereditary ATTR

Amyloidosis ● Global

GivosiranAcute Hepatic

Porphyrias ● Global

FitusiranHemophilia and Rare

Bleeding Disorders ● 15-30%

Royalties

Inclisiran Hypercholesterolemia ● Milestones & up

to 20% Royalties

ALN-

TTRsc02ATTR Amyloidosis ● Global

LumasiranPrimary Hyperoxaluria

Type 1 ● Global

CemdisiranComplement-Mediated

Diseases ● Global

Focused in 3 Strategic Therapeutic Areas (STArs):

Genetic Medicines

Cardio-Metabolic Diseases

Hepatic Infectious Diseases

5

LeoLiving with hATTR Amyloidosis5

LeoLiving with hATTR Amyloidosis

Description

Mutations in TTR gene lead to

deposition of misfolded protein

as amyloid, causing multi-system

disease manifestations1

Patisiran

Hereditary ATTR (hATTR) Amyloidosis

Patient Population*

~50,000worldwide

Significant morbidity

and fatal within

2-15years from symptom onset

GU:

Proteinuria

Kidney failure

UTI

Incontinence

Impotence

CARDIAC:

Heart failure

Arrhythmia

GI:

Diarrhea

Nausea

Vomiting

PERIPHERAL:

Numbness/tingling

Pain

Weakness

Impaired walking

AUTONOMIC:

Falls

Lightheadedness

Weight loss

1Coelho T, et al. N Engl J Med. 2013;369(9):819-829

*Ando et al., Orphanet J Rare Dis, 2013; Ruberg et al., Circulation, 2012

6

99% of patients who completed APOLLO study enrolled in Global OLE study

Randomized, Double-Blind, Placebo-Controlled Study in hATTR Amyloidosis

Patients with Polyneuropathy

Phase 3 Study Design

*To reduce likelihood of infusion-related reactions, patients received following premedication or equivalent at least 60 min before each study drug infusion:

10 mg (low dose) dexamethasone; oral acetaminophen; H1 and H2 blockers.

Patisiran

0.3 mg/kg

IV q3W*

Placebo

IV q3W*

or2

:1 R

AN

DO

MIZ

AT

ION

Primary Endpoint• Change in mNIS+7 from baseline at 18 months

Select Exploratory

Endpoints• EQ-5D QOL

• NIS+7

• Serum TTR levels

• Cardiac

assessments

• Grip strength

• Skin biopsies for

nerve fiber density

and amyloid

Secondary

Endpoints• Norfolk QOL-DN

• NIS-weakness

• Activities of daily

living (R-ODS)

• 10-meter walk

• mBMI

• Autonomic

function

(COMPASS-31)

ClinicalTrials.gov Identifier: NCT01960348

Patient Population

• hATTR amyloidosis:

any TTR mutation,

FAP Stage 1 or 2

• Neurological

impairment score (NIS)

of 5-130

• Includes patients with

NYHA Class 1 or 2

cardiac disease

OLE, open-label extension; ClinicalTrials.gov Identifier: NCT02510261

Adams D, et al. BMC Neurology 2017

7

Phase 3 Study Results

• -6.0 point change relative to baseline

• 34.0 point difference relative to placebo

• 56.1% of patients improved*

• -6.7 point change relative to baseline

• 21.1 point difference relative to placebo

• 51.4% of patients improved*

All secondary endpoints encompassing QOL, walk speed, activities of daily living and autonomic dysfunction met

Patisiran Met Primary and all Secondary Endpoints

At 18 months At 18 months

Adams et al., EU-ATTR Meeting, Nov 2017

*Improvement defined as patients with <0 point increase from baseline to 18 months

PatisiranPlacebo

Improvement

Worsening

-10

-5

0

5

10

15

20

25

30

35

LS

me

an

(S

EM

) ∆

mN

IS+

7 f

rom

ba

se

lin

e

p=9.26 x 10-24

mNIS+7

Improvement

Worsening

Baseline 9 Months 18 Months-10

-5

0

5

10

15

20

LS

me

an

(S

EM

) ∆

No

rfo

lk-Q

OL

fro

m b

as

eli

ne

p=1.10 x 10-10

Norfolk-QOL

Baseline 9 Months 18 Months

8

Patisiran Met Key Exploratory Endpoints in Cardiac Subpopulation*

Phase 3 Study Results

Adams et al., EU-ATTR Meeting, Nov 2017

*Cardiac subpopulation: patients with pre-existing cardiac amyloid involvement without confounding medical conditions (i.e., patients

with baseline LV wall thickness ≥1.3 cm and no aortic valve disease or hypertension in medical history)

**p-values are nominal

Biomarker FunctionalEchocardiographic

LV Wall Thickness Longitudinal Strain 10MWT

PatisiranPlacebo

NT-proBNP

-350

-250

-150

-50

50

150

250

350

Me

dia

n ∆

NT

-pro

BN

P fro

m b

ase

line

a

t 1

8 m

os (

ng

/L)

p=7.74 x 10-8 **

0

Worsening

Improvement

Worsening

Improvement-0.12

-0.08

-0.04

0

0.04

0.08

0.12M

ea

n ∆

LV

wa

ll th

ickn

ess fro

m b

ase

line

a

t 1

8 m

os (

cm

)

p=0.0173**

Worsening

Improvement-1.5

-1

-0.5

0

0.5

1

1.5

Me

an

∆lo

ng

itu

din

al str

ain

fro

m b

ase

line

a

t 1

8 m

os (

%)

p=0.0154**

Worsening

Improvement

-0.4

-0.3

-0.2

-0.1

0

0.1

0.2

0.3

0.4

Me

an

∆1

0-M

WT

ga

it s

pe

ed

fro

m b

ase

line

a

t 1

8 m

os (

m/s

ec)

p=7.42 x 10-9 **

9

Phase 3 Study Results

Overall, 13 deaths in APOLLO study; no deaths considered related to study drug

• Similar frequency of deaths in patisiran and placebo

treatment groups

• Causes of death (e.g., cardiovascular, infection) consistent

with NH

Majority of AEs mild or moderate in severity

• Most common AEs more frequently observed in patisiran arm

vs. placebo included peripheral edema (29.7% vs. 22.1%)

and infusion-related reactions (18.9% vs. 9.1%)

– Both AEs decreased over time; IRRs led to discontinuation

in only 1 patient (0.7%); peripheral edema led to no

discontinuations

Additional notable safety findings

• Encouraging safety & tolerability in cardiac subpopulation

– Deaths in 5.6% of patisiran patients and 11.1% of

placebo patients

• No safety signals related to steroid pre-medication regimen

or TTR KD

• No safety signals regarding liver function tests, hematology

including thrombocytopenia, or renal dysfunction related

to patisiran

Encouraging Safety & Tolerability Profile

Type of Adverse Event,

Number of patients (%)

Placebo

(N=77)

Patisiran

(N=148)

Adverse event (AE) 75 (97.4)143

(96.6)

Severe AE 28 (36.4) 42 (28.4)

Serious AE (SAE) 31 (40.3) 54 (36.5)

AE w/ discontinuation 11 (14.3) 7 (4.7)

AE w/ withdrawal 9 (11.7) 7 (4.7)

Death 6 (7.8) 7 (4.7)

Adams et al., EU-ATTR Meeting, Nov 2017

10

hATTR Amyloidosis and APOLLO Assessments

Clinical

Manifestations

APOLLO

Assessments

Sensorimotor Nerves

• Loss of sensation

• Muscle weakness

• Impaired ambulation

• mNIS+7

• NIS-W subdomain

• QST subdomain

• Reflexes subdomain

• Norfolk-QOL

• R-ODS disability

• 10-MWT

• Grip strength

• AE profile

Autonomic Nerves

• Orthostatic hypotension

• Syncope/falls

• Constipation/diarrhea

• Urinary retention/UTIs

• mNIS+7

• Postural BP subdomain

• Norfolk-QOL

• Autonomic subdomain

• mBMI

• COMPASS-31

• Orthostatic hypotension

• GI & bladder subdomains

• AE profile

Heart

• Heart failure

• Arrythmias/syncope

• Impaired exercise tolerance

• NT-proBNP

• Echo longitudinal strain

• Echo LV thickness

• 10-MWT

• AE profile

Misfolded mutant & wild-type

TTR amyloid fibrils in circulation

deposit in nerves and tissues

of many organs

Mutant & wild-type

TTR in liver

Patisiran

11

hATTR Amyloidosis Market Opportunity

• ~50,000 hATTR

amyloidosis patients

worldwide with some

endemic hot-spots

• Continuum of

peripheral/autonomic

neuropathy and cardiac

symptoms

– >50% of patients with

neurologic phenotype

have cardiomyopathy

(“mixed phenotype”)

– >30% of patients with

cardiac phenotype have

neuropathy (“mixed

phenotype”)

Estimated Disease Prevalence

* Based on Alnylam estimates from interviews with key opinion leaders, THAOS registry, recent clinical trials and literature

** ROW prevalence includes only select countries (e.g., Japan, Brazil, Turkey); Prevalence likely higher (e.g., 36% of APOLLO

enrollment was from ROW countries)† Current diagnosis rates difficult to confirm and may be lower in initial launch years

Estimated Global Breakdown*

Current Diagnosis Rate†

Prevalence

U.S. EUCAN ROW**

PN

~3K

Mixed

8-12K

CM

15-22K

~10-30% ~20-50%

~7K

PN

1-3K

Mixed

2-4K

CM

~10-30%

~2K

PN

~4K

Mixed

~8K

CM

12

Building a Customer-Centric Organization

Patisiran Pathway to Market

Only product in hATTR amyloidosis, investigational or approved, to demonstrate disease reversal*

Fast Track

Orphan Drug Designation

Breakthrough Status

NDA submitted

☐ FDA approval

☐ U.S. launch

Accelerated Assessment

MAA submitted

☐ EMA approval

☐ Reimbursement

☐ EU launch

Staged build of >250

employees in customer-

facing activities WW

☐ J-NDA submission

☐ ROW submissions

☐ Japan launch

☐ ROW launches

Ongoing patient ID efforts

in U.S./EUCAN,

expanding WW

Manufacturing and supply

chain for U.S./EUCAN,

expanding WW

*Negative mean change from baseline for mNIS+7 and Norfolk QOL-DN scores

13

Diagnosis, Education, Patient Support, and Access are Key Priorities

Raising hATTR Awareness and Improving Care

Diagnosis

• Started 2014, expanded

in 2016

• Free genetic screening

• Now includes panels

for neuropathy, cardio

• >350 physicians

enrolled; >3000 tests,

identified ~300 patients

with hATTR mutations

• Screened heart failure

patients for prevalence

of TTR mutations

• >1000 enrolled,

identified 77 patients

with hATTR mutations

Education

hATTRbridge.com

HCP Website

Patient Website

hATTRamyloidosis.com

Data

Access

Expanded Access Program

• Providing expanded

access to patisiran to

patients who meet

program criteria

• Now open at >15 sites in

U.S.; compassionate use

ongoing in EU

Alnylam Patient Access

Principles

Big Data Projects

• Integrating data sources

to inform MD targeting

for field engagement

Advocacy

Support

Care Days

• Local support program in

partnership with local

KOLs

• Agenda includes disease

overview, tips for living

with hATTR, and support

and resources

• 4 programs hosted in

2017; total attendance

over 100 people

• Working collaboratively

to improve care for

hATTR

14

Advancing Continued Innovation for Patients with ATTR Amyloidosis

ALN-TTRsc02 Opportunity

Mean max TTR KD of 97.1%;

~80% TTR KD at nearly 1 year

after single 50 mg dose*

Expect to initiate

Phase 3 study

in Late 2018

Inotersen

52DOSES

PER YEAR

ALN-TTRsc02

4DOSES

PER YEAR

ANTICIPATED

Safety (N=80):• No SAEs and no

discontinuations

due to AEs

• All AEs mild or

moderate in severity

*As of data cutoff on 31May2017

Phase 1 Study – Healthy Volunteers

0.0

0.2

0.4

0.6

0.8

1.0

1.2

1.4

1 41 81 121 161 201 241 281 321

Me

an

[+

/-S

EM

] T

TR

Kn

ockd

ow

n

Re

lative

to

Ba

selin

e (

%)

Days Since First Dose

Placebo (N=20) 5mg (N=6)

25mg (N=6) 50mg (N=6)

100mg (N=6) 300mg (N=6)

0 40 80 120 160 200 240 280 320

-40

-20

0

20

40

60

100

80

15

Potential for Significant Expansion in ATTR Amyloidosis

ALN-TTRsc02 Market Opportunity*

hATTR

amyloidosis

Asymptomatic

hATTR carriers

Wild-type

ATTR amyloidosis patients

*Intended to be illustrative and not intended to represent specific estimates of patient numbers

RoseLiving with Porphyria16

RoseLiving with Porphyria16

Description

Family of ultra-rare orphan diseases causing incapacitating and potentially fatal attacks, leading to frequent hospitalizations and chronic pain

Givosiran

Acute Hepatic Porphyrias

Patient Population*

~5,000 Patients

with sporadic

attacks

in U.S./EU

~1,000Patients

with recurrent

attacks

in U.S./EU

Predominantly

female,

commonly misdiagnosed

Severe, burning pain

in abdomen, chest,

back

Weakness,

numbness,

respiratory failure

Confusion, anxiety,

seizures,

hallucinations

Lesions on sun-

exposed skin;

chronic/blistering

*ORPHANET; The Porphyria Consortium

17

Randomized, Double-Blind, Placebo-Controlled Study in Recurrent Attack

Porphyria Patients

Givosiran Interim Phase 1 Study Results*

Alnylam has global rights to givosiran program

*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

DURABILITY

Monthly

SC dose

regimen

Safety: Generally well tolerated (N=9)

• No drug-related SAEs and no discontinuations due to AEs

• 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

52

8681

73

Cohort 1 (N=3) Cohort 2 (N=3) Cohort 3 (N=3)Mean Cohort 1-3

(N=9)

Mean

% D

ecre

ase i

n A

nn

ualized

Att

ack R

ate

73% Mean Decrease in Annualized Attack Rate

Givosiran Compared to Placebo

30

40

10

60

70

20

50

0

80

90

2.5 mg/kg

q3M

(N=3)

2.5 mg/kg

qM

(N=3)

5 mg/kg

qM

(N=3)

All

Cohorts

(N=9)

Giv

osir

an

–P

ati

en

t 3 (

2.5

mg

/kg

q3M

)

TreatmentRun-in

0

20

40

60

80

100

120

140

160

-100 -50 0 50 100 150

mmol/mol/Cr

Study Day

PBG

ALA

Heme

Porphyria Attack

Run-in Period Treatment Period

18

Randomized, Double-Blind, Placebo-Controlled Study in Acute Hepatic Porphyria

Patients

Phase 3 Study Design

Interim analysis planned in mid-2018

Givosiran

SC qM

2.5 mg/kg

Placebo

SC qM

or

N ~ 75

Patient Population

• Age ≥ 12 years

• Diagnosis of AHP

• ≥ 2 attacks within prior 6 months

• Willing to discontinue and/or not initiate hemin prophylaxis

1:1

RA

ND

OM

IZA

TIO

N

Primary Endpoint• Attacks requiring

hospitalization, urgent

care visit, home IV hemin

at 6 months

Key Secondary

Endpoints• ALA and PBG

• Hemin doses

• Symptoms

• QOL

Open-Label

Extension

FDA Breakthrough

and EMA PRIME

Designations

Statistical Considerations:

• 70 patients will have at least 90% power to detect 45% reduction in annualized attack rate at 2-sided alpha of 0.05

• Unblinded interim analysis of urinary ALA levels in 30 patients at 3 months

• Includes blinded assessment to adjust sample size for primary endpoint

19

Phase 3 Study

Alignment with FDA that reduction of urinary ALA is reasonably likely to predict clinical benefit

• Interim analysis with ~30 patients after 3 mo dosing; expect topline data in mid-2018

• Expect NDA submission in Late 2018 and potential FDA approval in mid-2019

Interim Analysis for Potential Accelerated Approval

*Sardh et al., ICPP, June 2017; Includes attacks treated in healthcare facility or with hemin

Urinary

ALA

(m

mol/m

ol cre

atinin

e)

0

6

12

18

24

30

36

42

48

54

60

Time, Days

-120 -90 -60 -30 0 30 60 90 120 150 180

ULN

2.5 mg/kg/mo (N=3)

placebo (N=4)

Treatment PeriodRun-In Period

Relationship of ALA Lowering

with Annualized Attack Rate*ALA Lowering in Recurrent Attack Patients at 2.5 mg/kg qM

0

5

10

15

20

25

30

Annualiz

ed A

ttack R

ate

≤0% >25-50% >50-75%>0-25% >75%

ALA increased

from baselineMore ALA lowering from patient’s baseline

20

Givosiran Market Opportunity

Givosiran has potential to address significant

unmet needs

• Current treatment options inadequate

• 65% of patients have chronic symptoms during and

between attacks

Significant economic burden

• Average annual expenditure ranging from approximately

$400,000 to $650,000, not reflecting indirect costs

Disease significantly under-diagnosed

• Long diagnostic journey that can exceed 10 years

• Frequency of gene mutation (2-5:100,000) suggests

much larger opportunity

Education efforts underway to drive improved

diagnosis and disease awareness

• Primary focus on neurologists, hematologists,

gastroenterologists

• Partnerships with patient advocacy groups

Initial opportunity in

recurrent population

Potential for further

expansion

Variegate porphyria

Hereditary coproporphyria

Sporadic attacks

Expanding ALNYLAM

ACT to porphyria

patients

21

Other Programs to Watch

22

Description

Genetic deficiency results in inability to

generate thrombin and stop bleeding,

leading to recurrent bleeds into joints,

muscles, and major internal organs

DURABILITY

Monthly

SC fixed

dose regimen

Fitusiran

Hemophilia and Rare Bleeding Disorders (RBD)

PATIENT

POPULATION

200,000worldwide

4,000with inhibitors

Re-initiated Phase 2 OLE and ATLAS

Phase 3 studies in December 2017;

Expect topline ATLAS results in 2019

39

Preliminary Fitusiran Phase 3 Program*Plan to Initiate in Early 2017

*Preliminary plans subject to further diligence and health authority feedback;

Patients in ATLAS studies will be allowed to roll over into open-label extension

• Adults and adolescents

with hemophilia A or B

with inhibitors

• On-demand

• N~50

2:1

Fitusiran

OD BPA

Endpoints:

• ABR

• Bypassing agent

(BPA) consumption

• Quality of life

• Safety

OR

• Adults and adolescents

with hemophilia A or B

with or without

inhibitors

• Prophylaxis

• N~100

FitusiranPPX

Factor/BPA

Endpoints:

• ABR

• Factor/BPA

consumption

• Quality of life

• Safety

• Adults and adolescents

with hemophilia A or B

without inhibitors

• On-demand

• N~100

2:1

Fitusiran

OD Factor

Endpoints:

• ABR

• Factor VIII or IX

consumption

• Quality of life

• Safety

OR1Clinical results as of Jun 15, 2017; Pasi et al., ISTH, July 2017; updated to reflect cerebral venous sinus thrombosis case

noted in safety box

*Sanofi Genzyme is leading and fully funding development (post-transition) of fitusiran

Fitusiran Phase 2 OLE Study in Inhibitor Patients*

Median ABR=0with 6 months [1-11] median duration of dosing in observation period1

38

0

0

5

10

15

20

25

30

35

40

N=14Pre-Study

N=14Fitusiran Treatment

Me

dia

n A

BR

Updated Safety in Phase 2 OLE (N=33):• 3 SAEs considered possibly related to study drug

– Includes one fatal cerebral venous sinus thrombosis – enhanced bleed

management guidelines and risk mitigation measures added to study

protocols following event

• Majority of AEs mild or moderate in severity, unrelated to study drug

• Reversible ALT increases >3x ULN in 11 (33%) patients, all with prior history of

HCV infection

23

>50% mean LDL-C loweringat Day 180 after two quarterly doses1

Safety (N=501)1:

• 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

Description

Highly prevalent disease caused by

elevated levels of LDL-C that

increase risk of atherosclerotic

cardiovascular disease (ASCVD)

Inclisiran ORION-1 Phase 2 Study*

DURABILITY

Biannual

SC dose

regimen

Inclisiran

Hypercholesterolemia

PATIENT

POPULATION

~31 million

in U.S. have

LDL-C levels

>240 mg/dl

Completed Phase 3 enrollment

with ~3,500 patients;

Expect topline results in 2019

1ORION-1 Phase 2 Study; ESC, Aug 2017

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

commercialize program, if successful

24

Lumasiran (ALN-GO1)

Primary Hyperoxaluria Type 1

Description

Rare autosomal recessive

disorder of increased oxalate

synthesis resulting in kidney

stone formation and renal

failure

Part B Safety (N=8):

• No drug-related SAEs (most common: kidney stones (N=2))

• No discontinuations

• Majority of AEs mild or moderate

Lumasiran Phase 1/2 Study; Initial Low-Dose Cohort (1 mg/kg, q4W)

>50% mean reduction in oxalate excretion1

Expect to initiate Phase 3

study in late 2018

PATIENT

POPULATION

~3-5,000

in U.S./EU

1Phase 1/2 Study; Frishberg et al., ASN, Nov 2017

24

h U

rin

e O

xa

late

co

rre

cte

d f

or

BS

A

(mm

ol/2

4h

r/1

.73

m2)

0.2

0.4

0.6

0.8

1.0

1.2

1.4

1.6

1.8

2.0

2.2

Study Day-20 0 20 40 60 80 100 120 140 160 180 200

LumasiranPlacebo

Delayed initial dosing of lumasiran

in patient randomized to placebo

ULN: 0.46

FDA Breakthrough

and EMA PRIME

Designations

25

Cemdisiran (ALN-CC5)

Complement-Mediated Diseases

Description

Numerous debilitating diseases

caused by abnormal complement

activity

• Paroxysmal nocturnal

hemoglobinura (PNH), atypical

hemolytic-uremic syndrome (aHUS),

myasthenia gravis, neuromyelitis

optica, membranous nephropathy

Part A Safety (N=20):

• No SAEs

• No discontinuations due to AEs

• All reported AEs mild or moderate

Mean max C5 knockdown of 98%; Durability supports qM to q3M SC

dose regimen1

Cemdisiran Phase 1/2 Study in Healthy Volunteers

PATIENT

POPULATION

~5,000 aHUS

>100,000 total complement-

mediated diseases

Expect Phase 2 aHUS

initial data in late 20181Data as of 03/02/2016

Me

an

(+

/-S

EM

) C

5 k

no

ck

do

wn

re

lati

ve

to

ba

se

lin

e (

%)

100

80

60

40

20

0

-20

-40

Days since first visit

0 40 80 120 160 200 240 280

50 mg (N=3)

200 mg (N=3)

400 mg (N=3)

900 mg (N=3)

Placebo (N=5)

600 mg (N=3)

26

ALN-AAT02

Alpha-1 Antitrypsin (AAT) Deficiency Associated

Liver Disease

Description

Orphan disease where mutant

AAT misfolds and aggregates

in hepatocytes, leading to liver

cirrhosis

IND/CTA filing

expected in late 2018;

1st program to employ

ESC+ platform

PATIENT

POPULATION2

~12,000

worldwide

1Seghal et al., DDW, May 20152Stoller et al., GeneReviews, 2014

Nucleus

ALN-AAT Preclinical Study in Tg-PiZ mice1

Placebo-Treated ALN-AAT-Treated

27

HSD17B13 Target

Nonalcoholic Steatohepatitis (NASH)

Description

Progressive disease

characterized by hepatic fat

buildup and inflammation,

potentially leading to cirrhosis

• Hepatocyte expressed intracellular target

amenable to RNAi therapeutic approach

• Loss-of-function variant (TA) associated with

reduced risk of chronic liver disease,

including NASH

HSD17B13 as a novel target1

1Abul-Husn et al. NEJM 2018 378;12, 10962Spengler et al. Mayo Clinic Proceedings. 2015;90(9):1233-1246

PATIENT

POPULATION2

>9 millionadults in U.S.

TA/TA (Variant)

Better

T/T (WT)

Better

28

UK Biobank Consortium

World-leading effort to connect genotype to full medical records for

phenome-wide association studies

• Goal to generate 500K exome sequences linked to medical records by end-2019

– 50K exomes sequenced to date

• Consortium members receive broad, ongoing access to UK Biobank data linked

to exome sequences

– Exclusive for 1 year after generation

Substantial value to Alnylam R&D efforts

• Modern drug discovery must incorporate human genetics

• Provides additional genetic validation for existing programs

• Identify/de-risk new programs

• In silico natural history data for new and existing programs

• Patient finding efforts

29

Guidance and Goals

30

31

2018*Early Mid Late

PATISIRAN(hATTR Amyloidosis)

Additional APOLLO Phase 3 data

FDA approval

U.S. launch

J-NDA submission

EMA approval

EU launch

Additional ROW submissions

GIVOSIRAN(Acute Hepatic Porphyrias)

Additional Phase 1/Phase 2 OLE data

ENVISION Phase 3 interim analysis topline

NDA filing

Complete ENVISION Phase 3 enrollment

FITUSIRAN(Hemophilia and RBD)

Continue ATLAS Phase 3 enrollment

ALN-TTRsc02(ATTR Amyloidosis)

Start Phase 3

INCLISIRAN(Hypercholesterolemia)

Complete ORION 9/10/11 (LDL-C) enrollment

Start ORION 4 (CVOT) Phase 3

LUMASIRAN(Primary Hyperoxaluria Type 1)

Start Phase 3

ADDITIONAL CLINICAL

PROGRAMS

Continue to advance early/mid-stage pipeline;

File new INDs; Present clinical data

Alnylam 2018 Goals*Early is Q1-Q2, Mid is Q2-Q3, and Late is Q3-Q4

32

Financial Summary and Guidance

2017 Q4 Financial Results

• Cash $1.73B

– Includes $30.0M in restricted

investments

• GAAP Revenues $37.9M

• Total GAAP Operating Expenses

$185.2M

– R&D Expenses $117.8M

– G&A Expenses $67.4M

• Total Non-GAAP Operating

Expenses* $158.1M

– Non-GAAP R&D Expenses* $102.9M

– Non-GAAP G&A Expenses* $55.2M

• GAAP Net Loss $142.2M

• Non-GAAP Net Loss* $115.1M

• Shares Outstanding 99.7M

2018 Financial Guidance

• Cash, including restricted cash and

restricted investments of ~$1.0B

• Annual Non-GAAP Operating

Expenses

– Non-GAAP R&D Expenses* in the

range of $400 to $440M

– Non-GAAP SG&A Expenses* in the

range of $280 to $320M

* Non-GAAP measures exclude stock-based compensation expenses.

33

To those who say “impossible, impractical, unrealistic,” we say:

CHALLENGE ACCEPTED

© 2018 Alnylam Pharmaceuticals, Inc.

To those who say “impossible, impractical, unrealistic,” we say:

CHALLENGE ACCEPTED

© 2018 Alnylam Pharmaceuticals, Inc.