third quarter 2018 financial results
TRANSCRIPT
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November 7, 2018
Third Quarter 2018 Financial Results
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Welcome• Christine Lindenboom
Vice President, Investor Relations & Corporate Communications
Q3 2018 Overview• John Maraganore, Ph.D.
Chief Executive Officer
Alnylam Clinical Pipeline• Akshay Vaishnaw, M.D., Ph.D.
President of R&D
Commercial Highlights• Barry Greene
President
Financial Summary and Guidance• Manmeet Soni
Chief Financial Officer
2018 Goals Update• Yvonne Greenstreet, MBChB
Executive Vice President, Chief Operating Officer
Q&A Session
Agenda
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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; successfully
launching, marketing and selling its approved products globally, its ability to successfully expand the indication for ONPATTRO in the
future; 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-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 expenses adjusted to exclude certain non-cash expenses and
non-recurring gains outside the ordinary course of the Company’s business. These measures are not in accordance with, or an
alternative to, GAAP, and may be different from non-GAAP financial measures used by other companies. The items included in GAAP
presentations but excluded for purposes of determining non-GAAP financial measures for the periods presented herein are stock-
based compensation expense and the gain on litigation settlement. The Company has excluded the impact of stock-based
compensation expense, which may fluctuate from period to period based on factors including the variability associated with
performance-based grants for stock options and restricted stock units and changes in the Company’s stock price, which impacts the
fair value of these awards. The Company has excluded the impact of the gain on litigation settlement because the Company believes
this item is a one-time event occurring outside the ordinary course of the Company’s business.
Alnylam Forward Looking Statements
& Non-GAAP Financial Measures
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Q3 2018 Overview
John Maraganore, Ph.D.
Chief Executive Officer
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Goal to Bring Innovation to Patients and Markets Around World
2018
ONPATTRO is indicated in the
U.S. for the treatment of the
polyneuropathy of hereditary
transthyretin-mediated
amyloidosis in adults^
Partnered programs*: 2020-2021
Fitusiran Inclisiran
Hemophilia Hypercholesterolemia
2019 2020 2021
Givosiran Lumasiran TTRsc02
Acute hepatic
porphyrias
Primary
hyperoxaluria
Type 1
ATTR
amyloidosis
* Sanofi Genzyme is leading and funding development (post-transition) of fitusiran and will commercialize program, if successful;
The Medicines Company is leading and funding development of inclisiran and will commercialize program, if successful
^ ONPATTRO is approved in the EU for the treatment of hATTR amyloidosis in adult patients with stage 1 or stage 2 polyneuropathy
Anticipated dates of launch based on current development timelines and assuming regulatory approval
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Alnylam Clinical Pipeline
Akshay Vaishnaw, M.D., Ph.D.
President of R&D
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Effects of Patisiran, an RNA Interference Therapeutic,
on Cardiac Parameters in Patients with Hereditary
Transthyretin-Mediated Amyloidosis:
An Analysis of the APOLLO Study
APOLLO Results Published in Leading Medical Journals
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Randomized, Open-Label Study in Hereditary ATTR Amyloidosis Patients
ALN-TTRsc02 Phase 3 Study
^ Primary endpoint for the study is at 9 months
* All-cause death and hospitalization endpoints assessed at 18 months only
Secondary Endpoints• 10-meter walk test (10-MWT)
• mBMI
• Activities of daily living (R-ODS)
• TTR reduction (within-study non-inferiority comparison)
• All-cause death and hospitalization (mITT)*
• All-cause death and hospitalization (patients w/ cardiac
involvement)*
Efficacy Assessments (vs APOLLO placebo)
Co-Primary Endpoints• Change in mNIS+7 from baseline
• Change in Norfolk QOL-DN from
baseline
Exploratory Endpoints Include
• NT-proBNP
• Echo parameters
• Technetium (select sites only,
change from baseline)
Patient Population
N ~ 160
• hATTR amyloidosis;
any TTR mutation
• Neuropathy
Impairment Score
(NIS) of 5-130
• Prior tetramer
stabilizer use
permitted
ALN-TTRsc02 25 mg SC
q3 months
Reference
Comparator
(patisiran)0.3 mg/kg
IV q3W
or
3:1
R
AN
DO
MIZ
AT
ION
ALN-TTRsc02
25 mg SC
q3 months
9-Month
Efficacy^Assessment
18-Month
EfficacyAssessment
Tre
atm
en
t E
xte
nsio
n
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Interim Results*Interim Efficacy Analysis & Safety
Interim analysis cohort• N = 43 AHP patients (41 AIP; 1 VP; 1 HCP)
• 23 randomized to givosiran; 20 randomized to placebo
• Treatment period: ≥3 months
Interim efficacy analysis (ALA levels at 3 months in AIP patients)• Statistically significant reduction in urinary ALA, relative to placebo (p < 0.001)
Safety• No deaths
• Serious Adverse Events (SAE) reported in:
• 5/23 (22%) of patients on givosiran
• 2/20 (10%) of patients on placebo
• One patient (4%) on givosiran discontinued treatment based on a protocol-defined stopping rule due to >8x ULN increase in liver transaminase, which resolved
• No treatment discontinuations in placebo group
Expect to initiate rolling NDA submission by year-end 2018
Topline results on completed Phase 3 study expected in early 2019
* Data cut-off date of August 22, 2018
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75% Mean Reduction in Urinary Oxalate
Lumasiran Phase 1/2 Study Updated Results*
* Part B data as of August 15, 2018; only data points with at least 3 contributing patients are represented; placebo data not shown due to limited valid collections† Patients randomized (3:1 drug:placebo) to placebo received subsequent dosing of lumasiran and are included in the lumasiran dosing cohort in which they were
randomized; Day 1 relative to first lumasiran dose; patient randomized to placebo 3 mg/kg quarterly received single dose of lumasiran on Day 1
Mean maximal reduction in urinary oxalate of 75% relative to baseline after lumasiran dosing in all cohorts (N=20)
Part B Safety (N=20):
• No discontinuations from study treatment
• Majority of AEs mild or moderate, unrelated to study drug
• AEs reported in >3 lumasiran patients: vomiting, pyrexia, cough (N=6); abdominal pain,
headache (N=5); rhinitis (N=4)
• No drug-related SAEs (most common: kidney stones (N=2 on lumasiran, 1 on placebo))
qMonth
†q3M
Mean [+
/-S
EM
] U
rine O
xala
te C
onte
nt
(mm
ol/24hr/
1.7
3m
2)
Lumasiran 1.0 mg/kg monthly (N=8)
Lumasiran 3.0 mg/kg monthly (N=8)
Lumasiran 3.0 mg/kg quarterly (N=4)
Day on Study
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Randomized, Double-Blind Study in Primary Hyperoxaluria Type 1 Patients
ILLUMINATE-A: Lumasiran Phase 3 Study
Patient Population
N = 30
• Adults & children ≥6 years
• Urinary oxalate excretion
≥0.7 mmol/24hr/1.73m2
• Confirmed alanine glyoxalate
aminotransferase (AGXT)
mutations
• eGFR >45 mL/min/1.73m2
2:1
Ra
nd
om
iza
tio
nLumasiran
3.0 mg/kg every 3 months
(following loading doses for patients
previously receiving placebo)
or
Lumasiran
Three monthly loading doses, then
maintenance dose of 3.0 mg/kg†
Placebo
Equivalent volume for 3 monthly
loading doses, then maintenance
6-Month Double Blind
Treatment Period 54-Month Extension Period
Secondary Endpoints• Change in 24-hour urinary
oxalate:creatinine ratio
• Proportion of patients with 24-hour urinary
oxalate leve below ULN and 1.5x ULN
• Change in eGFR
Primary Analysis at 6 Months
Primary Endpoint• Percent change in 24-hour urinary
oxalate excretion
Topline results expected in late 2019
NDA submission in early 2020
(assuming positive results)
FDA Breakthrough and EMA PRIME
Designations
† 3.0 mg/kg once monthly for 3 consecutive months (loading dose phase) followed by 3.0 mg/kg once every 3 months
(maintenance phase) starting 1 month after last loading dose
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Inclisiran & Fitusiran
Partnered Late Stage Programs
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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
OR
INCLISIRANhypercholesterolemia
FITUSIRANhemophilia and
rare bleeding disorders
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Alnylam Clinical Development PipelineFocused in 4 Strategic Therapeutic Areas (STArs):
Genetic Medicines
Cardio-Metabolic Diseases
Hepatic Infectious Diseases
CNS Diseases
1 POC, proof of concept – defined as having demonstrated target gene knockdown and/or additional evidence of activity in clinical studies2 Approved in the U.S. for the polyneuropathy of hATTR amyloidosis in adults, and in the EU for the treatment of hATTR amyloidosis in adult patients with
stage 1 or stage 2 polyneuropathy3 Includes marketing application submissions
As of September 2018
HUMAN
POC1
BREAKTHROUGH
DESIGNATIONEARLY STAGE
(IND or CTA Filed-Phase 2)
LATE STAGE (Phase 2-Phase 4)
REGISTRATION/
COMMERCIAL3
COMMERCIAL
RIGHTS
hATTR Amyloidosis2 ● Global
GivosiranAcute Hepatic
Porphyrias ● Global
FitusiranHemophilia and Rare
Bleeding Disorders ● 15-30% royalties
Inclisiran Hypercholesterolemia ● Milestones & up to
20% royalties
LumasiranPrimary Hyperoxaluria
Type 1 ● Global
ALN-TTRsc02 ATTR Amyloidosis ● Global
CemdisiranComplement-Mediated
Diseases ● Global
ALN-AAT02 Alpha-1 Liver Disease ● Subject to partner
option rights
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Limited Therapies to Prevent or Reverse Neurodegenerative Disease
RNAi Therapeutics in Development for CNS Diseases
Sequence specific target knockdown across brain and spinal cord in NHPs for two targets with single intrathecal dose*
• Confirmed siRNA uptake in several
different cell types
• Widespread distribution and
knockdown in all key anatomical
regions of brain and spinal cord tissue
• Successful translation to NHP with
robust silencing across CNS
* OTS 2018 Annual Meeting
Examples of dominantly inherited genes within
neurodegenerative diseases:
• Alzheimer’s disease
• Parkinson’s disease
• Frontotemporal dementia
• Huntington’s disease
• Amyotrophic lateral sclerosis (ALS)
• Spinocerebellar ataxia
Planned Next Steps
1st DC in late 2018
1st IND in late 2019/early 2020
1-2 INDs/year starting in 2020
Messag
e R
em
ain
ing
Lu
mb
ar
Sp
ine
Th
ora
cic
Sp
ine
Cerv
ical S
pin
e
Cere
bellu
m
Pre
fro
nta
l C
or t
ex
Tem
po
ral C
or t
ex
Hip
po
cam
pu
s
Bra
in S
tem
Liv
er
0 .0 0
0 .2 5
0 .5 0
0 .7 5
1 .0 0
1 .2 5
1 .5 0
P B S C o n tro l
C T N N B s iR N A
PBS
CTNNBTarget Gene Silencing in NHP CNS
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Commercial Highlights
Barry Greene
President
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Encouraging Initial Demand Through First 7 Weeks
ONPATTRO U.S. Launch Progress
125U.S. Patient
Start Forms
~60% from patients previously participating in patisiran EAP
NEUROLOGY CARDIOLOGY HEMATOLOGY
Start Form submissions received from key physician specialties, reflecting both
polyneuropathy & mixed patient phenotypes
Start Forms are requests submitted to Alnylam Assist patient hub to guide fulfillment of ONPATTRO prescriptions by physicians.
Submitted Start Forms do not reflect all demand.
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Global Commercialization Efforts Underway
EU and Asia in place
• EU launch underway (first
market in Germany)
• Japan team on-board
• Preparing Canada and
Switzerland
• Initiating Latin America,
starting with Brazil
Regional Support
• Market Access
• Supply Chain
Country organizations built
• Country Manager
• Medical Affairs
• Sales and Marketing
• Local Market Access
UNITED STATES CEMEA* LATIN AMERICA ASIA
* Canada, Europe, Middle East, North Africa
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U.S. Commercialization Underway
1 2 3
Diagnosis Brand Choice Treatment Experience
and Access
Unified Commercial, Market Access, & Medical Affairs teams driving disease education,
diagnosis & treatment, optimized patient experience, and access to care
TM
TM
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Financial Summary
and Guidance
Manmeet Soni
Chief Financial Officer
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Financial Summary and Guidance
2018 Q3 Financial Results
• Cash $1.27B
– Includes $44.8M in restricted investments
• ONPATTRO Net Product Revenues $0.5M
• Total GAAP Operating Costs and
Expenses $256.6M
– R&D Expenses $139.9M
– SG&A Expenses $116.6M
– Cost of Goods Sold $0.1M
• Non-GAAP Expenses
– Non-GAAP R&D Expenses* $94.2M
– Non-GAAP SG&A Expenses* $74.4M
• GAAP Net Loss $245.3M
• Non-GAAP Net Loss* $157.3M
• Shares Outstanding 101.0M
Re-Affirmed 2018 Financial Guidance
• Cash, including restricted cash and restricted
investments, of ~$1.0B
• Annual Non-GAAP Expenses
– Non-GAAP R&D Expenses* in the range of $420M to
$460M
– Non-GAAP SG&A Expenses* in the range of $280M to
$320M
* Non-GAAP measures and Non-GAAP Net Loss exclude stock-based compensation expenses
See Appendix for a reconciliation between GAAP and non-GAAP measures.
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2018 Goals Update
Yvonne Greenstreet, MBChB
Executive Vice President, Chief Operating Officer
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Alnylam 2018 Goals 2018*Early Mid Late
PATISIRAN(hATTR Amyloidosis)
Additional APOLLO Phase 3 data
FDA approval
U.S. launch
J-NDA filing
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
*Early is Q1-Q2, Mid is Q2-Q3, and Late is Q3-Q4
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Q&A Session
Q3 2018 Financial Results
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THANK YOU
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Appendix
Q3 2018 Financial Results
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Alnylam Pharmaceuticals, Inc.Reconciliation of Selected GAAP Measures to Non-GAAP Measures
(In thousands, except per share amounts)