Alnylam Pharmaceuticals 8K Annual Health Care Conference | ALNY 7 Mar 12

March 7, 2012

Cowen and Company 32

Annual Health Care Conference

Exhibit 99.1

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 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, 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

third

parties

for

access

intellectual

property;

and

the

outcome of litigation, as well as those risks more fully discussed in our most

recent annual 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.

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

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

Keystone:

Adv

Biopharm.,

Jan

2010;

Oligo

Ther

Soc.,

Sep

2011

ALN-TTRSc

(GalNAc-Conjugate)

mg/kg

100

-20

100

-20

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

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

0.01 -

0.2

(n=12)

0.4

(n=3)

0.7

(n=3)

1.0

(n=5)

-20

-40

ALN-TTR01 Dose Cohorts (mg/kg)

* p=0.02

ALN-TTR

ALN-PCS

100

<0.15 mg/kg

0.15 mg/kg

ALN-PCS Dose Groups

p=0.028

Day Post Dose

% Target

Knockdown

100

RNAi Therapeutics Profile

Single

dose…

…Durable and reversible

(dosing q30-60 days)

Potent and rapid…

Potential for Major

Therapeutic

Impact

Alnylam 5x15™

Focused Product Development Pipeline for Innovative Medicines

RNAi for genetically defined disease

as core strategy

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

Alnylam 5x15™

Focused Product Development Pipeline for Innovative Medicines

RNAi for genetically defined disease

as core strategy

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

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 Vyndaqel™

(tafamidis) for FAP

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

ALN-TTR in clinical development

Targets mutant and wild-type TTR

Positive preliminary clinical results

with TTR01

ALN-TTR02 CTA accepted

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

ALN-TTR01

Control siRNA

Sciatic

nerve

Dorsal root

ganglion

Esophagus

Colon

Stomach

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; preliminary data reported Q4 ’11

Full data presentation H1 ’12

100

-20

-40

-60

Day Post Dose

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)

100

-20

-40

-60

0.4 mg/kg (n=3)

0.7 mg/kg (n=3)

1.0 mg/kg (n=4)

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

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

TTR protein

Vitamin A

RBP

Day Post Dose

siRNA Dose

Int'l.

Symp.

FAP,

Nov.

2011

Preliminary, Trial Ongoing

ALN-TTR Program

ALN-TTR02

>10-fold improved efficacy in

animal models

Uses proprietary 2

generation MC3 LNP

formulation

~90% Knockdown at 0.3

mg/kg

Potential for q30-q60 day

dosing

Oligo

Ther

Soc.,

Sep

2011

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 accepted

Expect start of study in H1 ’12 and data in Q3 ’12

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

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

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 (NovoSeven™) and

FEIBA

–

Very short half-life, requiring frequent dosing

–

Not optimally effective

*Gringeri et al., Blood;

102:2358-63(2003)

Protein C Target and ALN-APC Program

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 V

Leiden

)

Co-inheritance associated with milder

bleeding in hemophilia patients

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

(2007)

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 –

APC Resistance and FV

Leiden

in Hemophilia

Improved Hemostasis

in hemophilia (A or B) x FV

Leiden

mice

Improved Thrombin Generation

with FV

Leiden

in hemophilia A patient plasma

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

50:50 wt

FV:FV

Leiden

100% FV

Leiden

100% wt FV

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

Treatment

Infusion of

Clotting factors

+/-

Hemophilia

with FV

Leiden

ALN-APC Pre-Clinical Efficacy

Durable Silencing After Single Dose

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

PC (41 KD)

aPC (35 KD)

light

chain (21 KD)

ASH,

Dec.

2011

Hemophilia

Areas of Unmet Need

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 t

1/2

=2.5h)

<10% patients on prophylaxis

Significant number of bleeding

episodes annually

Potential for effective prophylaxis

Hemophilia

Areas of Unmet Need

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 t

1/2

=2.5h)

<10% patients on prophylaxis

Significant number of bleeding

episodes annually

Potential for effective prophylaxis

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

Alnylam 5x15™

Additional Programs

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 in Q1 ’12

Plan to report complete results in H1 ’12

ALN-PCS Phase I Study 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

B&W,

Jan.

2012

Preliminary, Trial Ongoing

Alnylam 5x15™

Programs

Definable Clinical Paths with Phase I POC

Program

Indication: Unmet Need

Phase I Serum

Biomarkers

Early

Development

Advanced

Development

ALN-TTR

ATTR:

Significant

morbidity

and

mortality

-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

•

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

•

Iron

•

Liver iron content

Dose/regimen for increase

in Hb

Increase in Hb/reduced red

cell transfusions

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

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

Financials and Goals

* * * * * * * * * * * * * * * * * * * * * * * * * *

Financial Summary

2011 Q4 Financial Results

Cash ~$261M

~$6.11 per share

GAAP Revenues ~$21M

Roche, Takeda, Cubist, and other licenses

GAAP Operating Expenses ~$34M

Includes non-cash stock-based compensation charges of ~$4M

Shares Outstanding ~43M

2012 Guidance

Year-end Cash >$250M

Alnylam Goals

Pipeline Goals 2012-2013

Additional Corporate Goals 2012

Additional partnerships

Year-end Cash >$250M

Thank You

Alnylam Pharmaceuticals (ALNY) 8-KAnnual Health Care Conference