Alnylam Pharmaceuticals Reports First Quarter 2019 Financial Results and Highlights Recent Period Activity

− Achieved First Quarter 2019 ONPATTRO^®
Global Net Product Revenues of $26.3 Million with Over 400 Patients on
Commercial Product Worldwide –

− Achieved Positive Results in ENVISION Phase 3 Study of Givosiran –

− Formed Broad Collaboration with Regeneron to Discover, Develop and
Commercialize RNAi Therapeutics Focused on Ocular and Central Nervous
System (CNS) Diseases –

− Strengthened Balance Sheet with New Equity-Based Capital and
Partnership-Based Funding –

CAMBRIDGE, Mass.–(BUSINESS WIRE)–Alnylam
Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics
company, today reported its consolidated financial results for the first
quarter 2019 and reviewed recent business highlights.

“The first quarter of 2019 and recent weeks were a remarkable period of
advancement for Alnylam toward our goal of building a leading
biopharmaceutical company. Specifically, we demonstrated good progress
in global commercialization of ONPATTRO, continued success in our R&D
efforts with positive Phase 3 results for givosiran, and a strong
commitment to future pipeline growth through our landmark ocular and CNS
disease alliance with Regeneron. In addition, we significantly
strengthened our balance sheet through both an equity offering in
January and partnership-based equity funding and cash that we’ll receive
upon closing of the Regeneron transaction,” said John Maraganore, Ph.D.,
Chief Executive Officer of Alnylam. “We believe we are now well
positioned to achieve our Alnylam 2020 goal of building a
multi-product, global biopharma company with a deep clinical pipeline
for future growth and a robust product engine for sustainable
innovation, a profile rarely achieved in our industry. Moreover, as
evidenced by the success of our ONPATTRO launch and the results of our
givosiran Phase 3 study in porphyria, we believe we’re delivering on our
most important goal of bringing potentially transformative medicines to
patients.”

“In the first quarter, we made significant progress in our global
commercialization of ONPATTRO, as we advanced our efforts to help
patients secure access to this important new medicine. With over 400
patients on commercial product, we’re very pleased with our team’s
launch execution in over 10 countries where ONPATTRO is now available,
and we look forward to continued growth in all existing and many new
countries in the months to come. Of note, we saw strong new patient
demand in the U.S. and EU in the first quarter, beyond the initial
stages of our launch that had been largely driven by conversion of
patients from our expanded access program as well as patients known to
clinical study sites,” said Barry Greene, President of Alnylam. “As we
reported last night, we believe an important highlight in our
commercialization efforts is the innovation we’ve demonstrated with
regard to patient access. Indeed, with 10 value-based agreements now
completed in the U.S. and with favorable HTA ratings and reimbursement
outcomes in key EU countries, we’re advancing our goal to ensure that
ONPATTRO reaches all patients in need.”

First Quarter 2019 and Recent Significant Corporate Highlights

Commercial Performance in First Quarter 2019

• Achieved global net product revenues for the first quarter of 2019 of
  $26.3 million for ONPATTRO.
• Attained over 400 patients worldwide on commercial ONPATTRO treatment
  since launch as of March 31, 2019.
• Received 77 Start Forms in the U.S. in the first quarter, with over 90
  percent from newly identified patients not previously treated in the
  ONPATTRO Expanded Access Program.
  • Start Forms in the first quarter came from a diverse range of
    prescribing physician specialties, including 55 percent from
    cardiologists and 35 percent from neurologists, with 65 percent of
    patients covered by Medicare.
  • In addition, the Company reports continued strength in the number
    of U.S. patients receiving ONPATTRO from channels outside of its
    Alnylam Assist patient hub where the Company does not receive
    Start Forms.
• Reported continued progress with value-based agreements (VBAs) with
  commercial payers in the U.S. and with market access efforts globally.
  • Since launch, Alnylam has achieved access to ONPATTRO, if
    prescribed, for greater than 90 percent of U.S. lives across
    commercial, Medicare, Medicaid, and other government payer
    categories. In addition, Alnylam has completed definitive VBAs
    with 10 commercial U.S. payers to date.
  • In the EU, Alnylam reported favorable Health Technology Assessment
    (HTA) ratings from health authorities in several countries,
    including in France (“ASMR III”), Germany (“considerable
    benefit”), Italy (“innovation status”), and the Netherlands where
    a first-of-its-kind VBA was reached with all health insurers to
    reimburse ONPATTRO. The Company remains on track with pricing and
    reimbursement procedures in nearly all EU markets, and encouraging
    discussions with authorities have progressed significantly over
    the quarter.

R&D Highlights

• Advanced patisiran (the non-branded name for ONPATTRO), an
  intravenously administered investigational RNAi therapeutic in
  development for the treatment of ATTR amyloidosis.
  • Obtained alignment with the U.S. Food and Drug Administration
    (FDA) on the design of APOLLO-B, a randomized, double-blind,
    placebo-controlled Phase 3 study of patisiran in hereditary and
    wild-type ATTR amyloidosis patients with cardiomyopathy, with the
    goal of starting the trial in mid-2019.
• Advanced vutrisiran (ALN-TTRsc02), a subcutaneously administered
  investigational RNAi therapeutic in development for the treatment of
  ATTR amyloidosis.
  • Continued enrollment in the HELIOS-A Phase 3 study of vutrisiran
    in hereditary ATTR amyloidosis patients with plans to initiate
    additional Phase 3 studies, including in hereditary and wild-type
    ATTR amyloidosis cardiomyopathy, in late 2019.
• Advanced givosiran, an investigational RNAi therapeutic in development
  for the treatment of acute hepatic porphyria (AHP).
  • Achieved positive
    results in the ENVISION Phase 3 study and presented data at
    the European Association for the Study of the Liver (EASL) 54^th
    Annual International Liver Congress.
  • On track to complete submission of a New Drug Application (NDA)
    and submit a Marketing Authorisation Application (MAA) for
    givosiran in mid-2019.
• Advanced lumasiran, an investigational RNAi therapeutic in development
  for the treatment of primary hyperoxaluria type 1 (PH1).
  • Continued enrollment in the ILLUMINATE-A Phase 3 study of
    lumasiran in PH1 patients aged six or older with mild-to-moderate
    renal impairment, and remain on track to report results by
    year-end 2019.
  • Presented new
    positive results from the ongoing Phase 2 open-label extension
    (OLE) study of lumasiran at the International Society of
    Nephrology (ISN) 2019 Annual Meeting.
  • Initiated ILLUMINATE-B, a global Phase 3 pediatric study of
    lumasiran in PH1 patients under six years of age.
• Alnylam’s partner, The Medicines Company, announced in April that the
  Independent Data Monitoring Committee for ongoing inclisiran Phase 3
  clinical trials (ORION 9, 10, and 11) conducted its sixth planned
  review of safety and efficacy data from the ORION trials and
  recommended that the trials continue without modification.
  • The safety database for inclisiran now provides more than 3,000
    patient-years of exposure to an RNAi therapeutic, representing the
    industry’s most comprehensive body of safety data for an RNA
    therapeutic.
• Alnylam’s partner, Sanofi, continues enrollment in the ATLAS Phase 3
  program with fitusiran in patients with hemophilia A or B with and
  without inhibitors.
• Advanced early- and mid-stage RNAi clinical pipeline.
  • Initiated a Phase 2 study of cemdisiran, an investigational RNAi
    therapeutic targeting complement C5 for the treatment of
    complement-mediated diseases, in IgA nephropathy.
  • Filed a Clinical Trial Authorisation (CTA) application and
    received approval to initiate a Phase 1 study of ALN-AGT, an
    investigational RNAi therapeutic targeting angiotensinogen (AGT)
    for the treatment of hypertension in high unmet need populations,
    including patients with resistant or refractory hypertension,
    chronic kidney disease or heart failure.

Additional Business Highlights

• Announced a broad collaboration with Regeneron Pharmaceuticals, Inc.
  to discover, develop, and commercialize RNAi therapeutics focused on
  ocular and CNS diseases. Subject to Hart-Scott-Rodino (HSR) clearance,
  the Company anticipates closing this transaction during the second
  quarter of 2019.
• Announced the conclusion of the research and option phase of the
  Company’s 2014 collaboration with Sanofi focused on advancing RNAi
  therapeutics for rare genetic diseases.
• Entered into a collaboration with 23andMe to support the addition of a
  new Genetic Health Risk report for Hereditary Amyloidosis
  (TTR-related), which will help 23andMe customers who have opted in to
  receive such reports learn more about their genetic risk for the three
  most common TTR variants in the United States (V122I, V30M, and T60A).
  Read more about the report here.

Upcoming Events in Mid-2019

• Alnylam expects to receive regulatory approvals for ONPATTRO in Japan
  and Canada.
• Alnylam plans to complete its rolling NDA submission and file an MAA
  for givosiran.
• Alnylam expects to complete enrollment in the ILLUMINATE-A Phase 3
  study of lumasiran.

• The Company also expects to initiate the ILLUMINATE-C Phase 3 study of
  lumasiran in patients with impaired renal function.

• Alnylam expects to initiate the APOLLO-B Phase 3 study of patisiran in
  hereditary and wild-type ATTR amyloidosis patients with cardiomyopathy.
• Alnylam’s partner, The Medicines Company, expects to report initial
  topline results from the inclisiran Phase 3 clinical trials in the
  third quarter.

Financial Results for the Quarter Ended March 31, 2019

“2019 is off to a strong start for Alnylam, as we ended the first
quarter with a balance sheet of $1.3 billion. During the quarter, our
financials were bolstered by encouraging ONPATTRO uptake as well as
proceeds from our January equity financing, and subsequently enhanced
with $800 million in additional cash expected to be received during the
second quarter upon close of our recently announced collaboration with
Regeneron,” said Manmeet Soni, Chief Financial Officer of Alnylam. “This
cash balance positions us for continued execution of potential
commercial launches on a global scale, while accelerating the
advancement of our promising pipeline of late- and early-stage programs.”

Cash and Investments
At March 31, 2019, Alnylam had cash,
cash equivalents and marketable debt securities and restricted
investments of $1.29 billion, as compared to $1.13 billion at December
31, 2018.

In January 2019, Alnylam sold an aggregate of 5,000,000 shares of its
common stock through an underwritten public offering at a price to the
public of $77.50 per share. As a result of the offering, Alnylam
received aggregate net proceeds of approximately $382 million.

Cash at March 31, 2019 excludes proceeds from the Regeneron
collaboration, which was announced after the quarter end and is subject
to customary closing conditions. On a pro forma basis, Alnylam
has cash, cash equivalents and marketable debt securities and restricted
investments of greater than $2 billion.

GAAP and Non-GAAP Net Loss
The net loss according to
accounting principles generally accepted in the U.S. (GAAP) for the
first quarter of 2019 was $181.9 million, or $1.73 per share on both a
basic and diluted basis, as compared to a net loss of $141.2 million, or
$1.41 per share on both a basic and diluted basis, for the same period
in the previous year.

The non-GAAP net loss for the first quarter of 2019 was $149.9 million,
or $1.42 per share on both a basic and diluted basis, as compared to a
non-GAAP net loss of $121.6 million, or $1.22 per share on both a basic
and diluted basis for the same period in the previous year.

See “Use of Non-GAAP Financial Measures” below for a description of
non-GAAP financial measures and a reconciliation between GAAP and
non-GAAP net loss appearing later in this press release.

ONPATTRO Revenues, Net
Net product revenues from sales of
ONPATTRO were $26.3 million in the first quarter of 2019.

Net Revenues from Collaborators
Net revenues from
collaborators were $7.0 million in the first quarter of 2019 as compared
to $21.9 million in the first quarter of 2018.

GAAP and Non-GAAP Research and Development Expenses
GAAP
research and development (R&D) expenses were $129.1 million in the first
quarter of 2019 as compared to $96.9 million in the first quarter of
2018.

Non-GAAP R&D expenses were $113.0 million in the first quarter of 2019
as compared to $86.7 million in the first quarter of 2018. Non-GAAP R&D
expenses exclude stock-based compensation expense. A reconciliation
between GAAP and non-GAAP R&D expenses appears later in this press
release.

GAAP and Non-GAAP Selling, General and Administrative Expenses
GAAP
selling, general and administrative (SG&A) expenses were $89.6 million
in the first quarter of 2019 as compared to $72.4 million in the first
quarter of 2018.

Non-GAAP SG&A expenses were $73.7 million in the first quarter of 2019
as compared to $63.0 million in the first quarter of 2018. Non-GAAP SG&A
expenses exclude stock-based compensation expense. A reconciliation
between GAAP and non-GAAP SG&A expenses appears later in this press
release.

2019 Updated Financial Guidance
Alnylam is updating its 2019
annual non-GAAP R&D expenses to be in the range of $550 to $590 million
and non-GAAP SG&A expenses to be in the range of $390 to $410 million.
Both non-GAAP R&D and non-GAAP SG&A expenses exclude stock-based
compensation expenses. The increase in non-GAAP R&D guidance of $30
million is due primarily to third party obligations based on assumed
closing of the Regeneron collaboration during the second quarter.

The Company expects its current cash, cash equivalents, and marketable
debt securities will support company operations for multiple years based
upon its current operating plan.

Use of Non-GAAP Financial Measures
This press release
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 in the
press release 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.

The Company believes the presentation of non-GAAP financial measures
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 and are better able to
compare the Company’s performance between periods. In addition, these
non-GAAP financial measures are 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 measures
is provided later in this press release.

The Company does not provide in this press release a reconciliation of
its estimated 2019 non-GAAP R&D and non-GAAP SG&A expense guidance to
the comparable GAAP measures because it is not able to estimate 2019
stock-based compensation expense without unreasonable efforts. The
Company’s stock-based compensation expense is subject to significant
fluctuations from period to period due to variability in the probability
of performance-based vesting events for stock options and restricted
stock units and changes in the Company’s stock price which materially
impacts the recognition, timing of expense and fair value of these
awards. In addition, the Company believes such reconciliations for its
2019 financial guidance would imply a degree of precision that would be
confusing or misleading to investors.

Conference Call Information
Management will provide an
update on the Company and discuss first quarter 2019 results as well as
expectations for the future via conference call on Wednesday, May 1,
2019 at 8:30 am ET. To access the call, please dial 800-289-0438
(domestic) or 323-794-2423 (international) five minutes prior to the
start time and refer to conference ID 4935120. A replay of the call will
be available beginning at 11:30 am ET on the day of the call. To access
the replay, please dial 888-203-1112 (domestic) or 719-457-0820
(international) and refer to conference ID 4935120.

About ONPATTRO^® (patisiran)
Patisiran,
based on Nobel Prize-winning science, is an intravenously administered
RNAi therapeutic targeting transthyretin (TTR) for the treatment of
hereditary ATTR amyloidosis. It is designed to target and silence TTR
messenger RNA, thereby blocking the production of TTR protein before it
is made. Patisiran blocks the production of TTR in the liver, reducing
its accumulation in the body’s tissues in order to halt or slow down the
progression of the disease. In August 2018, patisiran received FDA
approval for the treatment of the polyneuropathy of hATTR amyloidosis in
adults, as well as European Medicines Agency marketing authorization for
the treatment of hATTR amyloidosis in adults with Stage 1 or Stage 2
polyneuropathy.

Important Safety Information

Infusion-Related Reactions
Infusion-related reactions
(IRRs) have been observed in patients treated with ONPATTRO. In a
controlled clinical study, 19 percent of ONPATTRO-treated patients
experienced IRRs, compared to 9 percent of placebo-treated patients. The
most common symptoms of IRRs with ONPATTRO were flushing, back pain,
nausea, abdominal pain, dyspnea, and headache.

To reduce the risk of IRRs, patients should receive premedication with a
corticosteroid, paracetamol, and antihistamines (H1 and H2 blockers) at
least 60 minutes prior to ONPATTRO infusion. Monitor patients during the
infusion for signs and symptoms of IRRs. If an IRR occurs, consider
slowing or interrupting the infusion and instituting medical management
as clinically indicated. If the infusion is interrupted, consider
resuming at a slower infusion rate only if symptoms have resolved. In
the case of a serious or life-threatening IRR, the infusion should be
discontinued and not resumed.

Reduced Serum Vitamin A Levels and Recommended Supplementation
ONPATTRO
treatment leads to a decrease in serum vitamin A levels. Supplementation
at the recommended daily allowance (RDA) of vitamin A is advised for
patients taking ONPATTRO. Higher doses than the RDA should not be given
to try to achieve normal serum vitamin A levels during treatment with
ONPATTRO, as serum levels do not reflect the total vitamin A in the body.

Patients should be referred to an ophthalmologist if they develop ocular
symptoms suggestive of vitamin A deficiency (e.g. night blindness).

Adverse Reactions
The most common adverse reactions
that occurred in patients treated with ONPATTRO were respiratory-tract
infection (29 percent) and infusion-related reactions (19 percent).

About LNP Technology
Alnylam has licenses to Arbutus
Biopharma LNP intellectual property for use in RNAi therapeutic products
using LNP technology.

About RNAi
RNAi (RNA interference) is a natural cellular
process of gene silencing that represents one of the most promising and
rapidly advancing frontiers in biology and drug development today. Its
discovery has been heralded as “a major scientific breakthrough that
happens once every decade or so,” and was recognized with the award of
the 2006 Nobel Prize for Physiology or Medicine. By harnessing the
natural biological process of RNAi occurring in our cells, a new class
of medicines, known as RNAi therapeutics, is now a reality. Small
interfering RNA (siRNA), the molecules that mediate RNAi and comprise
Alnylam’s RNAi therapeutic platform, function upstream of today’s
medicines by potently silencing messenger RNA (mRNA) – the genetic
precursors – that encode for disease-causing proteins, thus preventing
them from being made. This is a revolutionary approach with the
potential to transform the care of patients with genetic and other
diseases.

About Alnylam Pharmaceuticals
Alnylam (Nasdaq: ALNY) is
leading the translation of RNA interference (RNAi) into a new class of
innovative medicines with the potential to transform the lives of people
afflicted with rare genetic, cardio-metabolic, hepatic infectious, and
central nervous system/ocular diseases. Based on Nobel Prize-winning
science, RNAi therapeutics represent a powerful, clinically validated
approach for the treatment of diseases with high unmet need. ONPATTRO^®
(patisiran) is the first-ever RNAi therapeutic approved by the U.S. FDA
for the treatment of the polyneuropathy of hereditary
transthyretin-mediated (hATTR) amyloidosis in adults and by the EMA for
the treatment of hATTR amyloidosis in adults with stage 1 or stage 2
polyneuropathy. Alnylam has a deep pipeline of investigational
medicines, including six product candidates in Phase 3 studies. Looking
forward, Alnylam will continue to execute on its “Alnylam 2020”
strategy of building a multi-product, commercial-stage biopharmaceutical
company with a sustainable pipeline of RNAi-based medicines to address
the needs of patients who have limited or inadequate treatment options.
Headquartered in Cambridge, MA, Alnylam employs over 1,000 people
worldwide. For more information, please visit www.alnylam.com
and engage with us on Twitter at @Alnylam
or on LinkedIn.

Alnylam Forward Looking Statements
Various statements in
this release concerning Alnylam’s future expectations, plans and
prospects, including, without limitation, Alnylam’s views with respect
to the potential for RNAi therapeutics, including patisiran, vutrisiran,
givosiran, lumasiran, inclisiran, fitusiran, cemdisiran, and ALN-AGT,
its plans for additional global regulatory filings and product launches
for ONPATTRO, its expectations regarding the status of pricing and
reimbursement procedures outside the U.S., its expectations regarding
the timing for the initiation of its APOLLO-B Phase 3 study of
patisiran, its plans to initiate additional Phase 3 studies for
vutrisiran in late 2019, its expectations regarding the complete
submission of an NDA for givosiran with the FDA and the filing of an MAA
for givosiran with the EMA, its expectations regarding the timing of
topline results from its ILLUMINATE-A Phase 3 study of lumasiran, its
plans to initiate the ILLUMINATE-C Phase 3 study of lumasiran, its
expectations regarding the timing of topline results to be reported by
The Medicines Company from the ORION-11, ORION-9 and ORION-10 studies of
inclisiran, its expected range of 2019 annual non-GAAP R&D expenses and
non-GAAP SG&A expenses, its expectations regarding the length of time
its current cash, cash equivalents and marketable debt securities will
support company operations based on its current operating plan, its
expectations regarding its cash position following the closing of its
alliance with Regeneron and the expected timing of such closing, and
expectations regarding its “Alnylam 2020” guidance for the advancement
and commercialization of RNAi therapeutics, constitute forward-looking
statements for the purposes of the safe harbor provisions under The
Private Securities Litigation Reform Act of 1995.

Contacts

Christine Regan Lindenboom
(Investors and Media)
617-682-4340

Josh Brodsky
(Investors)
617-551-8276

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