January 2012

Corporate Overview

Alnylam Forward Looking Statements

This presentation contains forward-looking statements. 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 those that we discuss 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.

2

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

3

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 dosing

4 Keystone: Adv in Biopharm., Jan 2010; Oligo Ther Soc., Sep 2011

ALN-TTRSc (GalNAc-Conjugate)

mg/kg

100

80

60

40

20

0

-20

% T

TR m

RN

A Si

lenc

ing

(R

elat

ive

to C

ontr

ol)

100

80

60

40

20

0

-20

% T

TR m

RN

A Si

lenc

ing

(Rel

ativ

e to

Con

trol

)

0.03 0.1 0.3 ALN-TTR02 (MC3-LNP)

mg/kg

Control 5.0 1.0 0.2 Control

RNAi Human Translation Achieved Multiple Alnylam Therapeutic Programs

5

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 relevant human

tissue levels achieved

Human Proof of Mechanism

Human Proof of Concept Human Clinical Efficacy

Positive, p<0.001

Pre-

Post-

5’ location along VEGF transcript 3’

RNAi Cleavage

0.01 - 0.2 (n=12)

0.4 (n=3)

0.7 (n=3)

1.0 (n=5)

60

40

20

0

-20

-40

% S

erum

TTR

Kno

ckdo

wn

at N

adir

Geo

met

ric M

ean

Rel

ativ

e to

B

asel

ine

and

Pla

cebo

ALN-TTR01 Dose Cohorts (mg/kg)

* p=0.02 *

ALN-VSP

ALN-TTR ALN-PCS

% S

ubje

cts

Ac

hiev

ing

LDL-

c Ta

rget

100

0

20

40

60

80

<0.15 mg/kg ≥ 0.15 mg/kg

ALN-PCS Dose Groups

p=0.028

Day Post Dose

% Target Knockdown

10 15 20 25 30 100

80

60

40

20

0

0 5

RNAi Therapeutics Profile

6

Single dose…

…Durable and reversible (dosing q30-60 days)

Potent and rapid…

60

Potential for Major Therapeutic Impact

Alnylam 5x15TM

Focused Product Development Pipeline for Innovative Medicines

RNAi for genetically defined disease as core strategy • 5 Key products in clinical development

through 2015 • Near term focus on TTR and APC

programs Product characteristics Genetically defined target/disease Existing Alnylam delivery platform Early biomarkers in Phase I Clear and rapid development Significant commercial opportunity

7

ALN-RSV

ALN-VSP

ALN-HTT

Partner Programs

Programs 1. ALN-TTR 2. ALN-APC 3. ALN-PCS 4. ALN-HPN 5. ALN-TMP

Alnylam 5x15TM

Focused Product Development Pipeline for Innovative Medicines

RNAi for genetically defined disease as core strategy • 5 Key products in clinical development

through 2015 • Near term focus on TTR and APC

programs Product characteristics Genetically defined target/disease Existing Alnylam delivery platform Early biomarkers in Phase I Clear and rapid development Significant commercial opportunity

8

ALN-RSV

ALN-VSP

ALN-HTT

Partner Programs

Programs 1. ALN-TTR 2. ALN-APC 3. ALN-PCS 4. ALN-HPN 5. ALN-TMP

Transthyretin (TTR)-Mediated Amyloidosis (ATTR) Program Unmet Need and Product Opportunity

RNAi to treat genetic disease • ATTR is significant orphan disease

» ~50,000 Patients worldwide • Clinical pathology

» Onset ~40 to >60 yr » Two predominant forms

– Familial amyloidotic polyneuropathy (FAP) – Familial amyloidotic cardiomyopathy (FAC)

» Peripheral sensorimotor neuropathy, autonomic neuropathy, and/or cardiomyopathy

» Fatal within 5-15 years • Current treatments limited

» Liver transplant current standard of care – <3,000 Patients eligible

» Recent EU approval of Pfizer’s VyndaqelTM (tafamidis) for FAP

9

TTR Target and ALN-TTR Program

Mutant TTR is genetic cause of ATTR • >100 Defined mutations; autosomal dominant • Misfolds and forms amyloid deposits in

nerves and heart • Wild-type TTR also accumulates in

amyloid plaques » Limits benefits of liver transplantation

• Additional validation in mouse genetic models

10 10

Gly6Ser

Leu12Pro

Val20Ile

Pro24Ser

Val28Met

Phe33Cys Phe33Ile

Phe33Leu Phe33Val

Lys35Asn

Asp38Ala

Glu42Asp Glu42Gly

Ala45Asp Ala45Ser Ala45Thr

Thr49Ala Thr49Pro

Glu51Gly

Gly53Glu

Leu55Arg Leu55Pro Leu55Gln

Thr59Lys

Glu61Lys

Ile68Leu

Lys70Asn

Ile73Val

Ser77Phe Ser77Thy

Glu89Gln Glu89Lys

Ala97Gly Ala97Ser

Pro102Arg

Ile107Val

Leu111Met

Tyr114Cys Tyr114His

Ala120Ser

Pro125Ser

Ala91Ser Thr118Met

Asp18Glu Asp18Gly

Ala25Ser Ala25Thr

Arg34Thr

Ala36Pro

Trp41Leu

Gly47Ala Gly47Arg Gly47Glu Gly47Val

Ser50Arg

Glu54Gln Glu54Gly

Leu58Arg Leu58His

Thr60Ala

Phe64Leu Phe64Ser

Tyr69His Tyr69Ile

Val71Ala

Asp74His

Ile84Asn Ile84Ser

His90Asn

Gln92Lys

Gly101Ser

Arg104Cys Arg104His

Ala109Thr Ala109Val Ala109Ser

Ser112Ile

Tyr116Ser

Thr119Met

Val122Ala Val122Ile

Val122 (-) Cys10Arg

Ser23Asn Phe44Ser

Ser52Pro

Val30Ala Val30Gly Val30Leu

Val30 Met

5’ UTR

3’ UTR

ALN-TTR in clinical development • Targets mutant and wild-type TTR • Positive clinical results with TTR01 • ALN-TTR02 CTA filed • ALN-TTRsc in R2D for 2012 IND

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

11

ALN-TTR01

Control siRNA

0

10

20

30

40

50

60

70

Sciatic nerve

Dorsal root ganglion

Esophagus Colon Stomach

Rel

ativ

e TT

R T

issu

e Le

vels

Control siRNA ALN-TTR01

Dorsal Root Ganglion

100%

98.8%

98.5%

97%

98.8%

Int’l Amyloidosis Symp., April 2010

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 tolerability of ALN-TTR01

Secondary Objectives • Characterize PK • Assess preliminary PD and clinical activity

» Serum TTR levels » Serum retinol binding protein (RBP) and vitamin A levels

Study Status • Dose escalation completed; full data presentation H1 ’12

12

100

80

60

40

20

0

-20

-40

-60

* *

* * % S

erum

TTR

Kno

ckdo

wn

Geo

met

ric M

ean

TTR

Rel

ativ

e to

Bas

elin

e

Day Post Dose 0 8 12 4

0.4 mg/kg (n=3) 0.7 mg/kg (n=3) 1.0 mg/kg (n=5)

Placebo (n=7)

*p < 0.05 (ANOVA, vs placebo)

41% Avg. nadir at ~ day 7 relative to placebo (p=0.02)

ALN-TTR01 Phase I Study Results Dose-Dependent TTR Knockdown

Single dose results in rapid, dose-dependent, and durable knockdown of serum TTR protein levels • All patients show TTR knockdown at 1.0 mg/kg, ranging from 25-81% • Average nadir at approximately Day 7 of 41% relative to placebo (geometric mean vs. placebo, p=0.02)

13

100

80

60

40

20

0

-20

-40

-60

% S

erum

TTR

Kno

ckdo

wn

Geo

met

ric M

ean

TTR

Rel

ativ

e to

Bas

elin

e

0.4 mg/kg (n=3) 0.7 mg/kg (n=3) 1.0 mg/kg (n=4)

0 8 12 16 20 4 24 28

Day Post Dose

Int'l. Symp. FAP, Nov. 2011 Preliminary, Trial Ongoing

siRNA Dose

ALN-TTR01 Phase I Study Results Robust RNAi in Patient at 1.0 mg/kg ALN-TTR01

14

• 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 28 100

80

60

40

20

0

TTR protein Vitamin A RBP

Day Post Dose

% S

erum

TTR

/Vit

A/R

BP

Kno

ckdo

wn

Rel

ativ

e to

Bas

elin

e an

d P

lace

bo

siRNA Dose

Int'l. Symp. FAP, Nov. 2011 Preliminary, Trial Ongoing

0 8 12 16 20 4 24 28

ALN-TTR Program ALN-TTR02

>10-fold improved efficacy in animal models • Uses proprietary 2nd

generation MC3 LNP formulation

• ~90% Knockdown at 0.3 mg/kg

• Potential for q30-q60 day dosing

15 Oligo Ther Soc., Sep 2011

% S

erum

TTR

Kno

ckdo

wn

Day Post Dose

100

80

60

40

20

0

0 5 10 15 20 25 30

ALN-TTR01 (1.0 mg/kg)

ALN-TTR02 (0.1 mg/kg)

Control

ALN-TTR02 (0.3 mg/kg)

siRNA Dose

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 levels » Serum RBP and vitamin A levels

Study Status • CTA filed • Expect start of study in H1 ’12 and data in Q3 ’12

16

Subcutaneous ALN-TTR Program ALN-TTRsc

ALN-TTRsc achieves sustained silencing in pre-clinical animal model • Multi-dose subQ regimen; once weekly • Sustained TTR silencing achieved over multi-week period • Product differentiation across ATTR patient populations; planned IND in H2 ’12

17 Keystone: Nuc. Acid Ther., Jan 2012

100

80

60

40

20

0

0 2 4 6 8 10 12 14 16 18

% S

erum

TTR

Kno

ckdo

wn

(R

elat

ive

to C

ontro

l)

ALN-TTRsc (5.0 mg/kg)

ALN-TTRsc (25.0 mg/kg)

q Weekly Dosing Post Dosing Period

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 of TTR by tafamidis » Disease stabilization using NIS-LL

endpoint • V30M transgenic mouse model data

» Complete amyloid regression with TTR knockdown by ALN-TTR01

18

~50% Lowering in AL Amyloidosis

~50% Lowering in AA Amyloidosis

Gillmore et al., Lancet; 358:24-9 (2001) Lachmann et al., Br J Haematol; 122:78-84 (2003)

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 familial amyloidotic polyneuropathy (FAP)

• Value supported by pharmacoeconomics » Delay/reduce liver transplant » Reduced co-morbidities, hospitalizations

• Concentrated provider base; active patient base • Significant expansion opportunities

» Pre-FAP onset (e.g., TTR mutation carriers) » Familial amyloidotic cardiomyopathy (FAC) » Senile systemic TTR amyloidosis » Includes product differentiation with ALN-TTRsc

19

Hemophilia Program Unmet Need and Product Opportunity

RNAi to treat hemophilia • Hemophilias are recessive X-linked monogenic

bleeding disorders » Hemophilia A: loss of function mutations in Factor VIII

– >40,000 Patients in EU/US » Hemophilia B: loss of function mutations in Factor IX

– ~9,500 Patients in EU/US

• Hemophilia A “inhibitor” patients define segment of highest unmet need and cost* » ~1/3 Patients with severe hemophilia A

– >6 Bleeds/year; >5 in-hospital days/year – >$300,000/year – Very poor quality of life

» Only available therapies: rFVIIa (NovoSevenTM) and FEIBA – Very short half-life, requiring frequent dosing – Not optimally effective

20 *Gringeri et al., Blood; 102:2358-63(2003)

Protein C Target and ALN-APC Program

21

Protein C (PC) is genetically defined target • Activated Protein C (APC) drives key

natural anticoagulant pathway » Inactivates factors Va and VIIIa » Attenuates thrombin generation

• Heterozygous PC deficiency associated with increased thrombin generation

• Expressed in liver; circulates in plasma

ALN-APC in R2D • Efficacy in pre-clinical animal models • IND Filing 2013

APC Resistance (i.e., Factor VLeiden) • Co-inheritance associated with milder

bleeding in hemophilia patients

Kurnik et al., Hematologica; 92:982-5 (2007)

No Co-Inheritance

With Co-Inheritance

First bleed age (range)

0.9 (0.1– 4.0)

1.5 (0.5 – 7.1)

Annual bleeding frequency (range)

6.0 (0 – 30)

1.8 (0 – 7)

Intrinsic system

FIXaFVIIa FVII

FVIIIa

Extrinsic system

FVa FV

FX

FXa

Fibrinogen Fibrin

Thrombin

Hemophilia B

Hemophilia A

Prothrombin

APC PC

FIX

FVIII

Blood clot

APC Resistance and FVLeiden in Hemophilia

Improved Hemostasis

in hemophilia (A or B) x FVLeiden mice

22

Improved Thrombin Generation with FVLeiden in hemophilia A patient plasma

van ‘t Veer et al., Blood; 90:3067-3072 (1997)

50:50 wt FV:FVLeiden

100% FVLeiden

100% wt FV

Schlachterman et al., J Thromb Hemost; 3:2730-7 (2005)

No Treatment

Infusion of Clotting factors +/-

Hem

ophi

lia A

Hemophilia with FVLeiden

Hem

ophi

lia B

ALN-APC Pre-Clinical Efficacy Durable Silencing After Single Dose

23

ALN-APC demonstrates potent efficacy after single dose • Single-dose i.v. administration; 0.3 mg/kg • mRNA silencing of 90% within 24h; durable efficacy for weeks • Significant reduction in Protein C plasma levels

Knockdown of Protein C protein levels Duration of silencing on Protein C mRNA Purified human protein C (ng)

ALN-APC Control siRNA

150 100

75

50

35

25

20

PC (41 KD) aPC (35 KD)

light chain (21 KD)

100

200

500

ASH, Dec. 2011

100

80

60

40

20

0

0 4 8 12 16

Prot

ein

C m

RN

A Si

lenc

ing

(% C

ontr

ol P

re-d

ose)

ALN-APC (0.3mg/kg)

Control siRNA (0.3mg/kg)

Time (days)

siRNA Dose

Hemophilia Areas of Unmet Need

24

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 therapy with

“on demand” regimens

• rFVIIa and FEIBA used with unreliable effectiveness

• Patients are very high risk and complicated to manage

• Potential for new effective therapy

• Current treatments: low efficacy and impractical (rFVIIa t1/2=2.5h)

» <10% patients on prophylaxis

• Significant number of bleeding episodes annually

• Potential for effective prophylaxis

Non

-inhi

bito

r pa

tient

s In

hibi

tor

patie

nts

Hemophilia Areas of Unmet Need

25

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 therapy with

“on demand” regimens

• rFVIIa and FEIBA used with unreliable effectiveness

• Patients are very high risk and complicated to manage

• Potential for new effective therapy

• Current treatments: low efficacy and impractical (rFVIIa t1/2=2.5h)

» <10% patients on prophylaxis

• Significant number of bleeding episodes annually

• Potential for effective prophylaxis

Non

-inhi

bito

r pa

tient

s In

hibi

tor

patie

nts

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 still exists » Poor QOL » Spontaneous bleeds » Joint deterioration » Frequent i.v. injections; >120 injections/yr » Inhibitor patients » Long-acting factors provide marginal benefit

• Potential fast path to approval – inhibitor patients » ~6,500 Patients in EU and US

• Value supported by pharmacoeconomics • Broader opportunities also exist

» Adjunct to “on demand” therapy in non-inhibitor patients » Other genetic bleeding disorders (e.g., von Willebrand disease) » Bleeding associated with trauma

26

Alnylam 5x15TM

Additional Programs

27

Severe Hypercholesterolemia • Significant unmet medical need

» Elevated LDL-C (“bad” cholesterol) is validated risk factor for coronary artery disease and MI

» >500,000 Patients with severe hypercholesterolemia

» Multiple genetically defined patient subgroups with increasing delineation

Refractory Anemia • Anemia of chronic disease (ACD)

across multiple populations » End-stage renal disease (ESRD) » Cancer » Chronic inflammatory disorders

• Significant unmet need: Cancer, ESRD

ALN-PCS • Targets both intracellular and

extracellular PCSK9 • Efficacy in multiple pre-clinical

animal models • Phase I study

» Positive Phase I preliminary results » Complete data in H1

• Partner for Phase II

ALN-HPN • Targets transferrin receptor type 2

(TFR2) • Efficacy in pre-clinical animal

models • Partner for Phase I

ALN-TMP • Targets transmembrane protease,

serine 6 (Tmprss6) • Efficacy in pre-clinical animal models

showing disease modifying effects • Partner for Phase I

Hemoglobinopathies • Need for disease-modifying therapy

in beta-thalassemia and sickle cell anemia

» >200,000 beta-thal patients WW » ~70,000 SCA patients in US

• Additional need for improved management of iron overload disorders

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 tolerability

Secondary Objectives • Characterize PK • Assess preliminary PD activity and clinical activity

» Plasma PCSK9 levels » Plasma LDL-C levels

Study Status • Phase I trial ongoing with planned dose escalation >0.25 mg/kg • Reported positive preliminary clinical results • Plan to report complete results in H1 ’12

28

ALN-PCS Phase I Study Preliminary Clinical 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 day 4

(p<0.05) with sustained effects through at least day 14 • No significant decreases in HDL-C

29

LDL-C, Day 14

ANOVA: p = 0.0098 50

40

30

20

10

0

Placebo 0.015 0.045 0.09 0.15 0.25 ALN-PCS dose (mg/kg)

% L

DL-

C K

nock

dow

n R

elat

ive

to B

asel

ine

Day

% P

CSK

9 K

nock

dow

n R

elat

ive

to B

asel

ine

and

Pla

cebo

80

60

40

20

0

-20

-40

-60

0 5 10 15 20 25

siRNA Dose

ALN-PCS dose (mg/kg)

0.015 0.045 0.090

0.150 0.250

n=3/dose

PCSK9

B&W, Jan. 2012 Preliminary, Trial Ongoing

Hemoglobinopathy Program TMPRSS6 Target and ALN-TMP Program

30

Hemoglobin Improvement

Control ALN-TMP

<

Improvement of Spleen Histology

WT WT

ALN-TMP in Research • siRNA optimization ongoing • Efficacy in pre-clinical animal

models showing disease- modifying effects

Tmprss6 is genetically validated target • Tmprss6 (matriptase-2) cleaves hemojuvelin (HJV) resulting in

reduced hepcidin • Expressed on hepatocytes; membrane bound • Hemoglobinopathies associated with anemia, extra-medullary

hematopoiesis, and iron overload • Disease-modifying efficacy in beta-thalassemia animal model1

TMP

RS

S6/

M

atrip

tase

-2 B

MPR

BMP

promoter

hepcidin

R-SMAD R-SMAD P

R-SMAD

P SMAD4

7.50

12.50

17.50

Control siRNA ALN-TMP

WT Th3/+

p<0.01

Hem

oglo

bin,

g/d

L

H J V

1Gardenghi et al., JCI; 120:4466-4477 (2010) ASH, Dec. 2011

Alnylam 5x15TM Programs

Definable Clinical Paths with Phase I POC

31

Program Indication: Unmet Need Phase I Serum

Biomarkers Early

Development Advanced

Development

ALN-TTR ATTR: Significant morbidity and mortality 45-60 yrs of age with neuropathy and cardiomyopathy

• TTR • Vitamin A • Retinol binding

protein

Dose/regimen for >50% TTR reduction

FAP: Improvement in neuropathy score (NIS-LL)

ALN-APC

Hemophilia: Significant bleeding, hospitalizations, and costs associated with severe hemophilias, including “Inhibitor” pts

• Protein C • Thrombin

generation • Thrombo-

elastography

Dose/regimen to normalize thrombin generation

Reduced #bleeds over 6-12 mo period

ALN-PCS

Severe Hypercholesterolemia: Significant morbidity and mortality associated with LDL-C >200 mg/dL

• PCSK9 • LDL-C

Dose/regimen for >50% LDL-C reduction

LDL-C reduction in genetically defined high risk population

ALN-HPN

Refractory Anemia: Poor QOL and need for blood transfusions, very high EPO and i.v. iron doses

• Hepcidin • Iron • Hb • Transferrin

saturation

Dose/regimen for serum hepcidin reduction and increase in Hb

>1 g/dL increase in Hb in refractory anemia patients

ALN-TMP Hemoglobinopathy: Chronic anemia (repeated transfusions, iron overload), extra-medullary hematopoiesis, poor QOL

• Hb • Iron • Liver iron content

Dose/regimen for increase in Hb

Increase in Hb/reduced red cell transfusions

Partner Programs

Respiratory Syncytial Virus (RSV) • Significant unmet medical need

» >125,000 Pediatric hosp./yr in US » >170,000 Adult hosp./yr in US

• No effective therapies to treat RSV

Liver Cancer • Prevalent solid tumor and common

site of metastatic disease » ~700,000/yr Incidence of HCC WW » ~500,000/yr Patients with liver mets

32

Huntington’s Disease • Significant inherited

neurodegenerative disease » Caused by mutations in huntingtin gene » ~30,000 US pts; ~150,000 at risk

ALN-RSV01 • Targets key viral gene blocking

replication • Phase IIb RSV-infected lung

transplant patient study ongoing » Enrollment complete; ~90 patients » Data in mid-2012

• 50-50 US partnership with Cubist • Partnered with Kyowa in Asia

ALN-VSP • Targets two distinct genes involved in

cancer pathways » KSP for proliferation; VEGF for

angiogenesis • Phase I liver cancer study completed

» Results reported at ASCO 2011 ─ ALN-VSP generally well tolerated ─ 41 Patients ─ 3 Patients on extension study

» Demonstrated clinical activity and RNAi POM ─ 64% Disease control at Phase II dose ─ 1 PR in endometrial cancer patient ─ RNAi demonstrated in biopsy samples

• Partner prior to Phase II

ALN-HTT • Targets huntingtin gene • Pre-clinical development

» IND candidate 2012 • Drug-device combination • Collaboration with CHDI and

Medtronic » Alnylam/Medtronic 50/50 in US » CHDI funding

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

33

Partner Programs Alnylam 5x15 Programs

ALN-RSV01

ALN-TTR02

ALN-TTRsc

ALN-VSP

ALN-PCS

ALN-HTT

ALN-APC

ALN-HPN

ALN-TTR01

ALN-TMP

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

34

>700 microRNAs in human genome • Regulate expression of

> 1/3 of all human genes • Entire biological

pathways • Whole new frontier for

pharmaceutical research

35

Financials and Goals

36

Financial Summary

2011 Q3 Financial Results • Cash ~$286M

» ~$6.70 per share • GAAP Revenues ~$21M

» Roche, Takeda, and other licenses

• GAAP Operating Expenses ~$33M » Includes non-cash stock-based compensation charges of ~$4M

• Shares Outstanding ~43M 2011 Guidance • Increased year-end cash guidance to ~$260M

Alnylam Goals Pipeline Goals 2012-2013

37

Additional Corporate Goals 2012 • Additional partnerships • 2012 Financial guidance to be provided in YE/Q4 financial results

» YE 2011 ~$260M

ALN-TTR02 H2 ’12 Q3 ’12 / H1 ’12

ALN-TTRsc H2 ’12 H1 ’13

ALN-TMP

ALN-VSP Partner ALN-RSV01 Mid-’12

ALN-HTT H2 ’12

Phase II Clinical Data IND/Phase I Pivotal

Aln

ylam

5x1

5 Pr

ogra

ms

Part

ner

Prog

ram

s

2013

ALN-HPN Partner

ALN-PCS / H1 ’12 Partner

ALN-APC H1 ’13 H2 ’13

Partner

Thank You

www.alnylam.com

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