Alnylam Pharmaceuticals Reports Fourth Quarter and Full Year 2018 Financial Results and Highlights Recent Period Activity

− Achieved Fourth Quarter 2018 ONPATTRO® Global Net Product Revenues
of $12.1 Million, with Over 200 Patients on Commercial Product in U.S.
and EU as of Year-End 2018 –

− Obtained Regulatory Alignment on APOLLO-B Phase 3 Study of
Patisiran in ATTR Amyloidosis with Cardiomyopathy and Initiated HELIOS-A
Phase 3 Study to Advance Vutrisiran to Market, Supporting Plan for
Sustained and Continuous Growth of ATTR Franchise –

− Advanced Additional Phase 3 Programs, Including Givosiran, with
Rolling Submission of New Drug Application (NDA) Initiated and Topline
ENVISION Phase 3 Results Expected in March, and Lumasiran, with
ILLUMINATE-A Phase 3 Study Initiated –

− Maintained Strong Balance Sheet with $1.13 Billion in Cash as of
Year-End 2018 –

− Provides 2019 Non-GAAP R&D and SG&A Expense Guidance –

CAMBRIDGE, Mass.–(BUSINESS WIRE)–Alnylam
Pharmaceuticals, Inc.
 (Nasdaq: ALNY), the leading RNAi therapeutics
company, today reported its consolidated financial results for the
fourth quarter and full year ended December 31, 2018 and reviewed recent
commercial and R&D highlights.

“In 2018, we saw the approval and launch of ONPATTRO, the world’s first
RNAi therapeutic, heralding the arrival of a whole new class of
medicines. With our planned APOLLO-B Phase 3 study to support potential
expansion of ONPATTRO to ATTR amyloidosis patients with cardiomyopathy
and advancement of subcutaneously administered vutrisiran in the
HELIOS-A Phase 3 study, we are committing further efforts to help ATTR
amyloidosis patients and to support our plans for the sustained and
continued growth in our ATTR amyloidosis franchise for years to come,”
said John Maraganore, Ph.D., Chief Executive Officer of Alnylam. “While
executing on our efforts to bring ONPATTRO to patients around the world,
we also made great strides advancing our pipeline of investigational
RNAi therapeutics. In 2019, we intend to execute on six Phase 3 programs
– of which two are being advanced together with partners – with Phase 3
data expected from three of these programs, and expect two NDA
submissions, assuming positive results. In the meanwhile, we’ll continue
to benefit from a sustainable RNAi research engine that we expect will
fuel future innovation and deliver important medicines for patients.”

“We are pleased with our commercial progress to date, as we strive to
make ONPATTRO available to patients around the world. Specifically, we
are encouraged by our fourth quarter 2018 results, with over 200
patients receiving treatment with commercial ONPATTRO in the U.S. and EU
since launch, reflecting what we believe to be strong patient and
physician demand and excellent performance by our customer-facing field
teams,” said Barry Greene, President of Alnylam. “In 2019, we’re focused
on continued execution of our ONPATTRO launch in the U.S. and EU, while
expanding our global commercial presence in Asia and Latin America.
Longer term, we’re excited by the opportunity for positive impact for
patients, patient families and caregivers, and meaningful growth
potential for our ATTR amyloidosis franchise.”

Fourth Quarter 2018 and Recent Significant Corporate Highlights

Commercial Performance at Year-End 2018

  • Achieved global net product revenues for the fourth quarter of 2018 of
    $12.1 million for ONPATTRO, and $12.5 million for the full year ended
    December 31, 2018.
  • Attained over 200 patients in the U.S. and EU on commercial ONPATTRO
    treatment.

    • Including patients on commercial drug and patients in clinical
      studies and in the Company’s global Expanded Access Program (EAP),
      approximately 550 total patients worldwide were being treated with
      patisiran.
  • Received a total of 250 Start Forms in the U.S., with approximately 50
    percent from patients not previously treated in the ONPATTRO EAP.

    • Start Forms came from a diverse range of prescribing physician
      specialties, including 44 percent from neurologists, 35 percent
      from cardiologists, and 21 percent from other specialties.
    • For Start Forms received, 62 percent of patients were covered by
      Medicare, 32 percent were covered by commercial insurers, and 6
      percent were covered by other government insurers.
  • Continued significant progress with value-based agreements (VBAs) with
    commercial payers in the U.S. and with market access efforts in the EU.

    • Since launch, Alnylam has completed definitive VBAs with Harvard
      Pilgrim Healthcare, Humana, and another top five U.S. payer.
      Additional VBAs are under negotiation with over 15 other
      commercial payers with the potential to cover over 90 percent of
      commercial lives in the U.S.
    • The Company announces today that it has advanced pricing &
      reimbursement procedures with authorities in 15 EU countries –
      representing the vast majority of the hATTR amyloidosis
      opportunity in Europe – with positive feedback from several EU
      payers. Recent examples include positive technology assessment
      reports from authorities in Germany and Sweden, the special
      innovation designation of ONPATTRO by the Italian authorities, and
      favorable alignment with authorities in The Netherlands, among
      others.

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.

    • Continued global efforts to bring ONPATTRO to patients with filing
      of a New Drug Submission (NDS) in Canada and a Marketing
      Authorisation Application (MAA) in Switzerland, which has now been
      accepted.
    • 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.

    • Initiated HELIOS-A Phase 3 study in hereditary ATTR amyloidosis
      with polyneuropathy.
    • Announced plans to initiate an additional Phase 3 study, HELIOS-B,
      of vutrisiran in hereditary and wild-type ATTR amyloidosis with
      cardiomyopathy in late 2019.
  • Advanced givosiran, an investigational RNAi therapeutic in development
    for the treatment of acute hepatic porphyria (AHP).

    • Initiated rolling submission of a New Drug Application (NDA) with
      plans to pursue full approval based on complete results – expected
      in March 2019 – from the ENVISION Phase 3 study. Assuming positive
      results, the Company expects to submit full clinical sections to
      the FDA in mid-2019.
    • Published data
      from Phase 1 study of givosiran
      in The New England Journal
      of Medicine.
    • Presented updated positive
      Phase 1/2 open-label extension (OLE) results
      at The Liver
      Meeting® 2018 of the American Association for the Study
      of Liver Diseases (AASLD).
  • Advanced lumasiran, an investigational RNAi therapeutic in development
    for the treatment of primary hyperoxaluria type 1 (PH1).

    • Initiated ILLUMINATE-A, a global Phase 3 pivotal trial of
      lumasiran in children and adult PH1 patients with preserved renal
      function. Alnylam expects to report topline results from
      ILLUMINATE-A in late 2019 and, if positive, submit filings for
      global regulatory approvals starting in early 2020.
    • Presented updated positive results from the Phase 1/2 study in PH1
      patients at the 2018
      European Society for Paediatric Nephrology (ESPN)
      and the American
      Society of Nephrology (ASN)
      annual meetings.
    • Announced alignment with the FDA on the trial design for
      ILLUMINATE-B, a Phase 3 study of lumasiran in PH1 patients less
      than six years of age with preserved renal function.
  • Alnylam’s partner, The Medicines Company, announced in January 2019
    that the Independent Data Monitoring Committee for the ongoing
    inclisiran Phase 3 clinical trials (ORION 9, 10, and 11) conducted its
    fifth 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 2,450
      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 fitusiran Phase
    3 ATLAS program in patients with hemophilia A or B with and without
    inhibitors.
  • Advanced early-stage RNAi pipeline programs.

    • Discontinued a Phase 2 study of cemdisiran in atypical hemolytic
      uremic syndrome (aHUS) due to recruitment challenges. Alnylam
      announces today that it has received regulatory approval to
      initiate a Phase 2 study of cemdisiran in IgA nephropathy.
    • Submitted a Clinical Trial Authorization (CTA) application for
      ALN-AAT02, an investigational RNAi therapeutic for the treatment
      of alpha-1 antitrypsin deficiency-associated liver disease
      (alpha-1 liver disease). Alnylam announces today that it has
      initiated a Phase 1 study of ALN-AAT02, with initial results
      expected in 2019.
    • With Vir Biotechnology, initiated a Phase 1/2 study of ALN-HBV02
      (also known as VIR-2218), with initial results expected in 2019.
    • Reported new
      platform innovations
      at the Oligonucleotide Therapeutics
      Society 2018 Annual Meeting, including pre-clinical results
      demonstrating potent, wide-spread, and highly durable CNS and
      ocular delivery of RNAi therapeutics in rats and non-human
      primates.
    • Selected its first CNS-targeted development candidate, ALN-APP, an
      investigational RNAi therapeutic targeting amyloid precursor
      protein (APP) for the treatment of cerebral amyloid angiopathy
      (CAA).

Additional Business Highlights

  • Entered into an exclusive distribution agreement with Medison Pharma
    for the commercialization of certain RNAi therapeutics in Israel.
  • Resolved all litigation worldwide with Silence Therapeutics.

Upcoming Events in Early 2019

  • Alnylam expects to report topline results from the ENVISION Phase 3
    study of givosiran in March 2019, and announces today that it plans to
    present full study results in an oral presentation at the The
    International Liver Congress™ 2019 of the European Association for the
    Study of the Liver (EASL) on Saturday, April 13, 2019 in Vienna,
    Austria.

Financial Results for the Quarter and Year Ended December 31, 2018

“We ended 2018 with cash and investments on our balance sheet of $1.13
billion, exceeding our 2018 guidance, and we’re pleased to have recently
strengthened our balance sheet further with our public offering in
January resulting in net proceeds of approximately $382 million,” said
Manmeet Soni, Chief Financial Officer of Alnylam. “Taken together with
our growing product revenues, we believe Alnylam is in a strong position
to continue executing on global commercialization plans while advancing
our pipeline of late- and early-stage programs.”

Cash and Investments

At December 31, 2018, Alnylam had cash, cash equivalents and marketable
debt securities and restricted investments, excluding equity securities,
of $1.13 billion, as compared to $1.73 billion at December 31, 2017.

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.

GAAP and Non-GAAP Net Loss

The net loss according to accounting principles generally accepted in
the U.S. (GAAP) for the fourth quarter of 2018 was $211.4 million, or
$2.09 per share on both a basic and diluted basis, as compared to a net
loss of $142.2 million, or $1.48 per share on both a basic and diluted
basis, for the same period in the previous year. For the year ended
December 31, 2018, the net loss was $761.5 million, or $7.57 per share
on both a basic and diluted basis, as compared to a net loss of $490.9
million, or $5.42 per share on both a basic and diluted basis, for the
prior year.

The non-GAAP net loss for the fourth quarter of 2018 was $183.5 million,
or $1.82 per share on both a basic and diluted basis, as compared to a
non-GAAP net loss of $115.1 million, or $1.20 per share on both a basic
and diluted basis for the same period in the previous year. The non-GAAP
net loss for the year ended December 31, 2018 was $624.3 million, or
$6.21 per share on both a basic and diluted basis, as compared to a
non-GAAP net loss of $398.1 million, or $4.40 per share on both a basic
and diluted basis, for the prior year.

The non-GAAP net loss excludes stock-based compensation expense and gain
on litigation settlement. 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 $12.1 million in the
fourth quarter of 2018. Net product revenues from sales of ONPATTRO were
$12.5 million in the year ended December 31, 2018.

Net Revenues from Collaborators

Net revenues from collaborators were $9.0 million in the fourth quarter
of 2018, as compared to $37.9 million in the fourth quarter of 2017. Net
revenues from collaborators were $62.4 million in the year ended
December 31, 2018, as compared to $89.9 million in the year ended
December 31, 2017.

GAAP and Non-GAAP Research and Development Expenses

GAAP research and development (R&D) expenses were $131.0 million in the
fourth quarter of 2018 as compared to $117.8 million in the fourth
quarter of 2017. GAAP R&D expenses were $505.4 million in the year ended
December 31, 2018 as compared to $390.6 million for the prior year.

Non-GAAP R&D expenses were $118.1 million in the fourth quarter of 2018
as compared to $102.9 million in the fourth quarter of 2017. Non-GAAP
R&D expenses were $424.9 million in the year ended December 31, 2018 as
compared to $338.8 million for the prior year. 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 $108.7
million in the fourth quarter of 2018 as compared to $67.5 million in
the fourth quarter of 2017. GAAP SG&A expenses were $382.4 million in
the year ended December 31, 2018 as compared to $199.4 million for the
prior year.

Non-GAAP SG&A expenses were $93.7 million in the fourth quarter of 2018
as compared to $55.2 million in the fourth quarter of 2017. Non-GAAP
SG&A expenses were $305.1 million in the year ended December 31, 2018 as
compared to $158.4 million for the prior year. 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 Financial Guidance

Alnylam expects its 2019 annual non-GAAP R&D expenses to be in the range
of $520 to $560 million and non-GAAP SG&A expenses to be in the range of
$390 to $420 million. Both non-GAAP R&D and non-GAAP SG&A expenses
exclude stock-based compensation expenses.

The Company expects its current cash, cash equivalents, and marketable
debt securities will support company operations for approximately two
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, we believe such reconciliations for our 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 fourth
quarter and year end 2018 results as well as expectations for the future
via conference call on Thursday, February 7, 2019 at 4:30 pm ET. To
access the call, please dial 800-667-5617 (domestic) or 334-323-0509
(international) five minutes prior to the start time and refer to
conference ID 4263166. A replay of the call will be available beginning
at 7:30 pm 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 4263166.

Alnylam – Sanofi Genzyme Alliance

Alnylam and Sanofi Genzyme, the specialty care global business unit of
Sanofi, established an alliance to accelerate the advancement of RNAi
therapeutics as a potential new class of medicines for patients around
the world with rare genetic diseases. The alliance enables Sanofi
Genzyme to expand its rare disease pipeline with Alnylam’s novel RNAi
technology and provides access to Alnylam’s R&D engine, while Alnylam
benefits from Sanofi Genzyme’s proven global capabilities to advance
late-stage development and, upon commercialization, accelerate market
access for these promising genetic medicines products.

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 U.S. Food and Drug Administration (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
improve the lives of people afflicted with rare genetic,
cardio-metabolic, hepatic infectious, and central nervous system
(CNS)/ocular diseases. Based on Nobel Prize-winning science, RNAi
therapeutics represent a powerful, clinically validated approach for the
treatment of a wide range of severe and debilitating diseases.

Contacts

Alnylam Pharmaceuticals, Inc.
Christine Regan Lindenboom
(Investors
and Media)
617-682-4340

Josh Brodsky
(Investors)
617-551-8276

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