Alnylam Presents Initial 2017 Pipeline Goals at R&D Day with Focus on Alnylam 2020 Strategy

CAMBRIDGE, Mass.–(BUSINESS WIRE)– Alnylam
Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics
company, is hosting its R&D Day in New York City today. During the
event, the Company will discuss its pipeline goals for 2017, focusing
primarily on three mid- to late-stage programs advancing toward
potential commercialization and on the path to achieving its Alnylam
2020 goals. The highlighted programs, all of which are expected to
be in Phase 3 trials or in registration in 2017, include patisiran in
development for the treatment of hereditary ATTR amyloidosis (hATTR)
with polyneuropathy, fitusiran in development for the treatment of
hemophilia and rare bleeding disorders, and givosiran (formerly ALN-AS1)
in development for the treatment of acute hepatic porphyrias. Alnylam
believes that all three investigational RNAi therapeutics have the
potential to become transformative medicines for patients afflicted with
these rare and ultra-rare orphan diseases with high unmet medical need.
In addition, Alnylam will present preliminary positive Phase 1 study
results for ALN-TTRsc02, an investigational RNAi therapeutic in
development for the treatment of ATTR amyloidosis.

“In the coming year, we look forward to the advancement of our mid- to
late-stage pipeline and the continued evolution of our organization, as
we prepare to make the planned transition from a development-stage
company toward a multi-product, commercial-stage biopharmaceutical
company,” said John Maraganore, Ph.D., Chief Executive Officer of
Alnylam. “As we near 2020, we continue to be focused on pipeline
execution and the building of capabilities that we believe will enable
us to achieve our Alnylam 2020 goals, bringing RNAi therapeutics
to patients in need around the world.”

2017 Pipeline Goals
Patisiran, an investigational RNAi
therapeutic in development for the treatment of hATTR with
polyneuropathy. Alnylam plans to:

• Complete APOLLO Phase 3 study in 2017.
  • The Company expects to report top-line data from the APOLLO Phase
    3 trial in mid-2017 and additional results in late 2017.
  • Assuming positive Phase 3 data, Alnylam plans to submit a New Drug
    Application (NDA) and Marketing Authorisation Application (MAA)
    for patisiran at year-end 2017.
• Present 36-month data from patients originally enrolled in the
  patisiran Phase 2 Open-Label Extension (OLE) study in late 2017.

Fitusiran, an investigational RNAi therapeutic for the treatment of
hemophilia and rare bleeding disorders. Alnylam plans to:

• Initiate the ATLAS Phase 3 program in early 2017.
  • The ATLAS program is expected to consist of three separate Phase 3
    trials: ATLAS-INH in severe hemophilia A and B patients with
    inhibitors; ATLAS-A/B in severe hemophilia A and B patients without
    inhibitors; and, ATLAS-PPX in severe hemophilia A and B patients
    with or without inhibitors, switching from prophylactic factor or
    bypassing agent therapy to fitusiran prophylaxis.
• Present data from ongoing fitusiran trials in mid- and late 2017.

Givosiran, an investigational RNAi therapeutic for the treatment of
acute hepatic porphyrias. Alnylam plans to:

• Present additional data from the ongoing randomized, double-blind,
  placebo-controlled Phase 1, Part C study in recurrent attack acute
  intermittent porphyria (AIP) patients in mid-2017.
• Initiate a givosiran Phase 3 trial in late 2017.

Alnylam also plans to continue support of The Medicines Company’s
advancement of inclisiran (formerly ALN-PCSsc) into Phase 3 studies in
early and mid-2017. In addition, the Company plans to continue
advancement of its earlier-stage clinical pipeline programs with
multiple data read-outs expected throughout 2017.

ALN-TTRsc02 Preliminary Phase 1 Data
The Company also
announced preliminary clinical data from its Phase 1 study of
ALN-TTRsc02, an investigational RNAi therapeutic in development for the
treatment of ATTR amyloidosis. The Phase 1 trial is a randomized,
placebo-controlled, single ascending-dose study in healthy volunteers
receiving fixed subcutaneous doses ranging from 5 mg to 300 mg.

New results (N=48) showed:

• Single subcutaneous doses of ALN-TTRsc02 achieved robust transthyretin
  (TTR) knockdown of up to 98.4 percent (mean max of 97.1 ± 0.5
  percent), with durability for well over four months. At a dose of 50
  mg, ALN-TTRsc02 achieved a mean knockdown at day 90 of 86.2%. Based on
  these results, the Company believes that a once-quarterly, fixed dose
  of 25 to 50 mg of ALN-TTRsc02 could achieve clamped and potentially
  clinically meaningful reductions exceeding 80% of TTR, the
  disease-causing protein in hATTR amyloidosis.
• In addition, ALN-TTRsc02 was generally well tolerated in healthy
  volunteers, with no serious adverse events and no discontinuations due
  to adverse events. All adverse events reported were mild or moderate
  in severity and included transient injection site reactions (redness
  and pain), pruritus, cough, nausea, fatigue and abdominal pain. No
  significant changes were reported in hematologic or laboratory
  parameters (e.g., liver function tests), vital signs or physical exams.

“At Alnylam, we remain committed to the goal of bringing RNAi
therapeutics to hATTR amyloidosis patients. We are encouraged by these
initial results from ALN-TTRsc02 and the broader advances of our
Enhanced Stabilization Chemistry (ESC) platform that have enabled an
over 100-fold improvement of potency and a meaningful improvement in
durability in our GalNAc-siRNA conjugate efforts,” said Eric Green, Vice
President, General Manager of the TTR Program. “Pending positive results
from the APOLLO Phase 3 study of patisiran, we plan to engage regulators
to align on a development path for ALN-TTRsc02. With potent TTR
knockdown and durability supportive of once-quarterly dosing, we believe
ALN-TTRsc02 has the potential to be a best-in-class therapeutic for
patients with all forms of ATTR amyloidosis.”

Sanofi Genzyme Alliance
In January 2014, Alnylam and Sanofi
Genzyme, the specialty care global business unit of Sanofi, formed an
alliance to accelerate and expand the development and commercialization
of RNAi therapeutics across the world. The alliance is structured as a
multi-product geographic alliance in the field of rare diseases. Alnylam
retains product rights in the United States, Canada and Western Europe,
while Sanofi Genzyme obtained the right to access certain programs in
Alnylam’s current and future Genetic Medicines pipeline in the rest of
the world (ROW) through the end of 2019, together with certain broader
co-development/co-commercialization rights and global rights for certain
products. In the case of patisiran, Alnylam will advance the product
in the United States, Canada and Western Europe, while Sanofi Genzyme
will advance the product in the ROW. In the case of fitusiran, Sanofi
Genzyme has elected to opt in to co-develop (through Sanofi R&D) and
co-commercialize fitusiran in the United States, Canada and Western
Europe, in addition to developing and commercializing fitusiran in its
ROW territories.

About RNAi
RNAi (RNA interference) is a revolution in
biology, representing a breakthrough in understanding how genes are
turned on and off in cells, and a completely new approach to drug
discovery and development. Its discovery has been heralded as “a major
scientific breakthrough that happens once every decade or so,” and
represents one of the most promising and rapidly advancing frontiers in
biology and drug discovery today which was awarded the 2006 Nobel Prize
for Physiology or Medicine. RNAi is a natural process of gene silencing
that occurs in organisms ranging from plants to mammals. By harnessing
the natural biological process of RNAi occurring in our cells, the
creation of a major new class of medicines, known as RNAi therapeutics,
is on the horizon. Small interfering RNA (siRNA), the molecules that
mediate RNAi and comprise Alnylam’s RNAi therapeutic platform, target
the cause of diseases by potently silencing specific mRNAs, thereby
preventing disease-causing proteins from being made. RNAi therapeutics
have the potential to treat disease and help patients in a fundamentally
new way.

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

About Alnylam Pharmaceuticals
Alnylam is a biopharmaceutical
company developing novel therapeutics based on RNA interference, or
RNAi. The company is leading the translation of RNAi as a new class of
innovative medicines. Alnylam’s pipeline of investigational RNAi
therapeutics is focused in 3 Strategic Therapeutic Areas (STArs):
Genetic Medicines, with a broad pipeline of RNAi therapeutics for the
treatment of rare diseases; Cardio-Metabolic Disease, with a pipeline of
RNAi therapeutics toward genetically validated, liver-expressed disease
targets for unmet needs in cardiovascular and metabolic diseases; and
Hepatic Infectious Disease, with a pipeline of RNAi therapeutics that
address the major global health challenges of hepatic infectious
diseases. In early 2015, Alnylam launched its « Alnylam 2020″ guidance
for the advancement and commercialization of RNAi therapeutics as a
whole new class of innovative medicines. Specifically, by the end of
2020, Alnylam expects to achieve a company profile with 3 marketed
products, 10 RNAi therapeutic clinical programs – including 4 in late
stages of development – across its 3 STArs. The company’s demonstrated
commitment to RNAi therapeutics has enabled it to form major alliances
with leading companies including Ionis, Novartis, Roche, Takeda, Merck,
Monsanto, The Medicines Company, and Sanofi Genzyme. In addition,
Alnylam holds an equity position in Regulus Therapeutics Inc., a company
focused on discovery, development, and commercialization of microRNA
therapeutics. Alnylam scientists and collaborators have published their
research on RNAi therapeutics in over 200 peer-reviewed papers,
including many in the world’s top scientific journals such as Nature,
Nature Medicine, Nature Biotechnology, Cell, New England Journal of
Medicine, and The Lancet. Founded in 2002, Alnylam maintains
headquarters in Cambridge, Massachusetts. For more information about
Alnylam’s pipeline of investigational RNAi therapeutics, please visit www.alnylam.com.

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, fitusiran,
givosiran, and ALN-TTRsc02, its expectations regarding the timing of
clinical studies and the presentation of clinical data, its expectations
regarding the filing of an NDA and MAA for patisiran, its expectations
regarding its STAr pipeline growth strategy, its « Alnylam 2020″ guidance
for the advancement and commercialization of RNAi therapeutics, and its
plans regarding the 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.
Actual results and future plans may differ materially from those
indicated by these forward-looking statements as a result of various
important risks, uncertainties and other factors, including, without
limitation, Alnylam’s ability to discover and develop novel drug
candidates and delivery approaches, successfully demonstrate the
efficacy and safety of its product candidates, the pre-clinical and
clinical results for its product candidates, which may not be replicated
or continue to occur in other subjects or in additional studies or
otherwise support further development of product candidates for a
specified indication or at all, actions or advice of regulatory
agencies, which may affect the design, initiation, timing, continuation
and/or progress of clinical trials or result in the need for additional
pre-clinical and/or clinical testing, delays, interruptions or failures
in the manufacture and supply of our product candidates, obtaining,
maintaining and protecting intellectual property, Alnylam’s ability to
enforce its intellectual property rights against third parties and
defend its patent portfolio against challenges from third parties,
obtaining and maintaining regulatory approval, pricing and reimbursement
for products, progress in establishing a commercial and ex-United States
infrastructure, competition from others using technology similar to
Alnylam’s and others developing products for similar uses, Alnylam’s
ability to manage its growth and operating expenses, obtain additional
funding to support its business activities, and establish and maintain
strategic business alliances and new business initiatives, Alnylam’s
dependence on third parties for development, manufacture and
distribution of products, the outcome of litigation, the risk of
government investigations, and unexpected expenditures, as well as those
risks more fully discussed in the « Risk Factors » filed with Alnylam’s
most recent Quarterly Report on Form 10-Q filed with the Securities and
Exchange Commission (SEC) and in other filings that Alnylam makes with
the SEC. In addition, any forward-looking statements represent Alnylam’s
views only as of today and should not be relied upon as representing its
views as of any subsequent date. Alnylam explicitly disclaims any
obligation, except to the extent required by law, to update any
forward-looking statements.

The scientific information referenced in this news release relating to
Alnylam’s investigational therapeutics is preliminary and investigative.
None of Alnylam’s investigational therapeutics have been approved by the
U.S. Food and Drug Administration, European Medicines Agency, or any
other regulatory authority and no conclusions can or should be drawn
regarding the safety or effectiveness of these therapeutics.

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