Alnylam Initiates ILLUMINATE-B Phase 3 Pediatric Study of Lumasiran for the Treatment of Primary Hyperoxaluria Type 1 and Presents New Positive Results from Phase 2 Open-Label Extension Study

− All Patients in Phase 1/2 Study Have Now Transitioned into Phase 2
OLE –

− Lumasiran Treatment Resulted in 72 Percent Mean Maximal Reduction
in Urinary Oxalate Relative to Phase 1/2 Baseline –

CAMBRIDGE, Mass.–(BUSINESS WIRE)–Alnylam
Pharmaceuticals, Inc.
 (Nasdaq:ALNY), the leading RNAi therapeutics
company, announced today that the Company has initiated ILLUMINATE-B, a
global Phase 3 pediatric study of lumasiran, an investigational,
subcutaneously administered RNAi therapeutic in development for the
treatment of primary hyperoxaluria type 1 (PH1). The study will enroll
approximately eight patients with PH1 under six years of age. The
primary endpoint is the percent reduction in urinary oxalate from
baseline to six months. The Company expects to report initial
ILLUMINATE-B results in mid-2020.

The Company also announced new positive efficacy results from the
ongoing Phase 2 open-label extension (OLE) study of lumasiran. The
results were presented at the International Society of Nephrology (ISN)
2019 Annual Meeting held on April 13-16 in Melbourne, Australia.

“We are pleased to start the ILLUMINATE-B pediatric trial, an important
step forward in our goal to assess the safety and efficacy of lumasiran
across the PH1 age and disease severity continuum, including patients in
early infancy. This study adds to our overall clinical development plan
for lumasiran, led by our ILLUMINATE-A pivotal study with results
expected by year-end 2019,” said Pritesh J. Gandhi, PharmD, Vice
President and General Manager, Lumasiran program at Alnylam. “We are
also pleased to report new results from our Phase 2 OLE study, and are
encouraged by the consistently sustained reductions we observe in
urinary oxalate and by the overall safety profile of lumasiran observed
thus far.”

All patients (N=20) from the Phase 1/2 study of lumasiran have now
transitioned to the Phase 2 OLE study designed to evaluate long-term
safety and efficacy of lumasiran. The new Phase 2 OLE results were
reported with 18 patients dosed in the OLE as of the data cut-off date
of February 8. Patients were on a range of lumasiran doses and regimens
(1.0 mg/kg monthly, 3.0 mg/kg monthly, and 3.0 mg/kg quarterly).

There were no discontinuations from study treatment. A single patient
(1/18; 5.6 percent) reported two serious adverse events (SAEs) of
traumatic brain injury and bone contusion sustained in a car accident;
neither was assessed as related to study drug. Adverse events (AEs) were
reported in 12/18 (66.7 percent) patients. Injection site reactions were
reported in 3/18 (16.7 percent) patients; all were mild and assessed as
related to study drug. There were no clinically significant laboratory
changes.

Lumasiran demonstrated a 72 percent mean maximal reduction (range: 41-90
percent) in urinary oxalate excretion relative to Phase 1/2 baseline
values across all dose cohorts (N=9). The mean reduction relative to
baseline at Day 85 was 69 percent (N=7). Lumasiran also demonstrated a
mean maximal reduction in urinary 24-hour oxalate:creatinine ratio of 77
percent (range: 57-91 percent) relative to Phase 1/2 baseline values
across all dose cohorts (N=10). The mean reduction relative to baseline
at Day 85 was 70 percent (N=9).

To view the results presented by Alnylam at ISN 2019 Annual Meeting,
please visit www.alnylam.com/capella.

About ILLUMINATE-B Phase 3 Study
The ILLUMINATE-B Phase 3
trial is an open-label, global, multicenter study to evaluate the
efficacy and safety of lumasiran in approximately eight patients less
than six years of age with a documented diagnosis of PH1. Dosing regimen
will be based on patient weight. The primary endpoint is the reduction
of urinary oxalate at six months relative to baseline. Key secondary and
exploratory endpoints will evaluate additional measures of urinary
oxalate, estimated glomerular filtration rate (eGFR), safety and
tolerability, and quality of life. For more information on ILLUMINATE-B
(NCT03905694) please visit www.clinicaltrials.gov,
email clinicaltrials@alnylam.com
or call 877-256-9526 in North America and +31 20 369 7861 in Europe.

About Lumasiran
Lumasiran (formerly known as ALN-GO1) is an
investigational RNAi therapeutic targeting glycolate oxidase (GO) in
development for the treatment of Primary Hyperoxaluria Type 1 (PH1).
Lumasiran is designed to reduce hepatic levels of the GO enzyme, thereby
depleting the substrate necessary for the production of oxalate – the
metabolite that directly contributes to the pathophysiology of PH1.
Lumasiran utilizes Alnylam’s Enhanced Stabilization Chemistry
(ESC)-GalNAc-conjugate technology, which enables subcutaneous dosing
with increased potency and durability and a wide therapeutic index.
Lumasiran has received both U.S. and EU Orphan Drug Designations, a
Breakthrough Therapy Designation from the U.S. Food and Drug
Administration (FDA), and a Priority Medicines (PRIME) designation from
the European Medicines Agency (EMA). The safety and efficacy of
lumasiran have not been evaluated by the FDA, EMA or any other health
authority.

About Primary Hyperoxaluria Type 1 (PH1)
PH1 is an
ultra-orphan disease in which excessive oxalate production results in
the deposition of calcium oxalate crystals in the kidneys and urinary
tract and can lead to the formation of painful and recurrent kidney
stones and nephrocalcinosis. Renal damage is caused by a combination of
tubular toxicity from oxalate, calcium oxalate deposition in the
kidneys, and urinary obstruction by calcium oxalate stones. Compromised
kidney function exacerbates the disease as the excess oxalate can no
longer be effectively excreted, resulting in subsequent accumulation and
crystallization in bones, eyes, skin, and heart, leading to severe
illness and death. Current treatment options are very limited and
include frequent renal dialysis or combined organ transplantation of
liver and kidney, a procedure with high morbidity that is limited due to
organ availability. Although a small minority of patients respond to
Vitamin B6 therapy, there are no approved pharmaceutical therapies for
PH1.

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 whole 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 (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. Founded in 2002, Alnylam is delivering
on a bold vision to turn scientific possibility into reality, with a
robust discovery platform. Alnylam’s first U.S. FDA-approved RNAi
therapeutic is ONPATTRO® (patisiran) lipid complex injection
available in the U.S. for the treatment of the polyneuropathy of
hereditary transthyretin-mediated (hATTR) amyloidosis in adults. In the
EU, ONPATTRO is approved for the treatment of hATTR amyloidosis in
adults with stage 1 or stage 2 polyneuropathy. Alnylam has a deep
pipeline of investigational medicines, including five product candidates
that are in late-stage development. 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. Alnylam
employs over 1,000 people worldwide and is headquartered in Cambridge,
MA. For more information about our people, science and pipeline, 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 potency, durability and therapeutic index of lumasiran and the
potential for lumasiran to address the significant unmet needs of PH1
patients, its expectations regarding the timing for reporting results
from the ILLUMINATE-A and ILLUMINATE-B clinical studies, and
expectations regarding “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. 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 its
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, successfully launching,
marketing and selling its approved products globally, Alnylam’s ability
to successfully expand the indication for ONPATTRO in the future,
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 Annual Report on
Form 10-K 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.

Lumasiran has not been approved by the FDA, EMA, or any other regulatory
authority and no conclusions can or should be drawn regarding the safety
or effectiveness of this investigational therapeutic.

Contacts

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

Josh Brodsky
(Investors)
617-551-8276