Dicerna™ Submits Updated IND Application for DCR-PHXC for Treatment of Primary Hyperoxaluria (PH) for the PHYOX™2 Pivotal Trial

– Update Reflects Alignment with FDA on Path to Full Approval for
Treatment of PH1 and Discussions Now Focusing on Appropriate Endpoints
for PH2 and PH3 –

CAMBRIDGE, Mass.–(BUSINESS WIRE)–Dicerna™
Pharmaceuticals, Inc. (Nasdaq:DRNA) (the “Company” or “Dicerna”), a
leading developer of investigational ribonucleic acid interference
(RNAi) therapeutics, today announced the submission of an updated
investigational new drug (IND) application to the U.S. Food and Drug
Administration (FDA) for DCR-PHXC, the Company’s lead GalXC™ product
candidate for the treatment of all forms of primary hyperoxaluria (PH).
The update reflects agreement on the primary endpoint for the PHYOX™2
pivotal clinical trial, which is enrolling patients with PH type 1 (PH1)
and PH type 2 (PH2), and alignment with the FDA regarding the path to
full approval for the treatment of patients with PH1, as conveyed during
a recent FDA Type A meeting. The Company will continue its ongoing
dialogue with the FDA regarding endpoints for studies involving patients
with PH2 and PH3, as part of the PHYOX clinical development program for
DCR-PHXC.

“We are pleased by the positive and constructive discussion with the FDA
regarding our DCR-PHXC program. The agency’s confirmation of the primary
endpoint for our pivotal trial provides a clear path forward to achieve
full approval of DCR-PHXC for the treatment of PH1,” said Ralf Rosskamp,
M.D., chief medical officer of Dicerna. “We also look forward to
continuing discussions with the FDA regarding the primary and secondary
endpoints in patients with PH2 and PH3, less prevalent subtypes of
primary hyperoxaluria for which there are relatively little natural
history data. We will continue to report our progress as the PHYOX
trials move forward.”

For the forthcoming pivotal PHYOX2 study, Dicerna reached agreement with
the FDA on a primary endpoint of 24-hour urinary oxalate burden,
expressed as the time-weighted standardized (TWS) area under the curve
(AUC) from Day 90 to 180, based on percent change from baseline. Dicerna
recently announced initiation of participant screening in the PHYOX2
trial, which will evaluate a multi-dose regimen of DCR-PHXC in
individuals with PH1 and PH2. The Company expects to begin enrolling
patients to the PHYOX2 trial in the second quarter of 2019.

“Urinary oxalate burden is increasingly recognized as an important issue
for patients with primary hyperoxaluria, as overproduction of oxalate is
implicated in all types of this devastating disease, for which there are
no approved therapies,” commented Craig Langman, M.D., a pediatric
nephrologist and the Isaac A. Abt, M.D. Professor of Kidney Diseases at
the Feinberg School of Medicine, Northwestern University and Head,
Kidney Diseases, at Lurie Children’s Hospital. “We expect that the PHYOX
trials will demonstrate reduction of oxalate, by targeting the lactate
dehydrogenase A enzyme, in the pathogenesis of PH2 and PH3.”

Dicerna recently presented updated data from the ongoing PHYOX1 Phase 1
clinical trial of DCR-PHXC, which showed post-dose reductions in 24-hour
urinary oxalate levels in adult and adolescent study participants with
PH1 and PH2. The PHYOX1 data also showed that a single dose of DCR-PHXC
led to normalization or near-normalization of urinary oxalate levels in
a majority of patients and was generally well-tolerated.

About DCR-PHXC
DCR-PHXC is an investigational drug in
development for the treatment of all forms of primary hyperoxaluria
(PH), and the most advanced product candidate utilizing Dicerna’s GalXC™
technology. GalXC is a proprietary platform invented by Dicerna
scientists to discover and develop next-generation RNAi-based therapies
designed to silence disease-driving genes in the liver. In animal models
of PH, DCR-PHXC selectively silences lactate dehydrogenase A enzyme, or
LDHA, in the liver, blocking the excess production of oxalate, a
hallmark of the disease. In preclinical studies of DCR-PHXC, the
compound was well tolerated with no adverse effects in the liver.
Studies have shown that people who are completely deficient in LDHA show
no liver dysfunction and can lead normal lives. LDHA deficiency in the
liver may be beneficial for patients with PH, as the LDHA enzyme is
implicated in the abnormal production of oxalate in PH, which in turn is
responsible for the severe damage to kidneys and other organs in
patients with PH.

About Primary Hyperoxaluria (PH)
Primary hyperoxaluria (PH)
is a family of severe, rare, genetic liver disorders characterized by
overproduction of oxalate, a natural chemical in the body that is
normally eliminated as waste through the kidneys. In patients with PH,
the kidneys are unable to eliminate the large amount of oxalate that is
produced, and the accumulation of oxalate can result in severe damage to
the kidneys and other organs. Currently, there are no approved therapies
for the treatment of PH. There are three known types of PH, each of
which results from a mutation in a specific gene, as well as PH for
which the molecular basis remains unknown, often referred to as “no
mutation detected” (NMD) PH or idiopathic PH (IPH). The known PH
mutations cause a decrease in the activity of a specific enzyme in the
liver, triggering an increase in oxalate production. In each case the
decreased enzyme activity changes the balance of intermediary
metabolites, resulting in overproduction of oxalate. The three
genetically known types of PH are: ^1,2

• PH1, which is caused by a mutation in the AGXT gene, causing a
  deficiency of the enzyme alanine:glyoxylate-aminotransferase (AGT),
• PH2, which is caused by a mutation in the GRHPR gene, causing a
  deficiency of the enzyme glyoxylate/hydroxypyruvate reductase
  (GR/HPR), and
• PH3, which is caused by a mutation in the HOGA1 gene, causing a
  deficiency of the enzyme 4-hydroxy-2-oxoglutarate aldolase (HOGA).

Patients with severe PH often undergo both liver and kidney transplants,
which are major surgical procedures, and subsequently must take
immunosuppressant drugs for the rest of their lives. Patients with
decreased renal function may also experience oxalosis, which involves a
build-up of oxalate in other organs such as the bone, skin, heart, and
retina, possibly causing other concomitant, debilitating complications.

PH occurs in an estimated 1 in 120,000 live births around the world.³ The
estimated genetic prevalence of PH1 is 1 in 151,887 births, which
implies more than 5,000 patients in the United States and European Union
have the disease.³ The estimated genetic prevalence of PH2 is
1 in 310,055 and that of PH3 is 1 in 135,866.³ The median age
at the first appearance of PH1 symptoms is 5.8 years.⁴ The
median age at diagnosis of PH1 is between 4.2 and 11.5 years, depending
on whether nephrocalcinosis (calcification in the renal parenchyma, the
functional part of the kidney) is present.⁵ Fifty percent of
patients with PH1 reach end-stage renal disease by their mid-30s.²

About Dicerna™ Pharmaceuticals, Inc.
Dicerna™
Pharmaceuticals, Inc., is a biopharmaceutical company focused on the
discovery and development of innovative, subcutaneously delivered
RNAi-based therapeutics for the treatment of diseases involving the
liver, including rare diseases, chronic liver diseases, cardiovascular
diseases and viral infectious diseases. Dicerna is leveraging its
proprietary GalXC™ RNAi technology platform to build a broad pipeline in
these core therapeutic areas, focusing on target genes where connections
between target gene and diseases are well understood and documented.
Dicerna intends to discover, develop and commercialize novel
therapeutics either on its own or in collaboration with pharmaceutical
partners. Dicerna has strategic collaborations with Eli Lilly and
Company, Alexion Pharmaceuticals, Inc. and Boehringer Ingelheim
International GmbH. For more information, please visit www.dicerna.com.

Cautionary Note on Forward-Looking Statements
This press
release includes forward-looking statements. Forward-looking statements
are subject to risks and uncertainties that could cause actual results
to differ materially from those expressed or implied in such statements.
Examples of forward-looking statements include, among others, statements
we make regarding: (i) the future discussions the Company plans to have
with the FDA regarding clinical endpoints for PH2 and PH 3 in the PHYOX
clinical trial; (ii) the monitoring and ultimate outcome of the PHYOX
clinical trial in PH1, PH2 and PH2 patients; research and development
plans and timelines related to DCR-PHXC; and (iii) the potential of
Dicerna™’s technology and DCR-PHXC in the Company’s research and
development pipeline. The process by which an early stage
investigational therapy such as DCR-PHXC and an early stage platform
such as GalXC could potentially lead to an approved product is long and
subject to highly significant risks. Applicable risks and uncertainties
include those relating to Dicerna’s clinical research and other risks
identified under the heading “Risk Factors” included in the Company’s
most recent Form 10-K filing and in other future filings with the
Securities and Exchange Commission. These risks and uncertainties
include, among others, the cost, timing and results of preclinical
studies and clinical trials and other development activities; the
likelihood of Dicerna’s clinical programs being executed within
timelines provided and reliance on the Company’s contract research
organizations and predictability of timely enrollment of subjects and
patients to advance Dicerna’s clinical trials; the potential for future
data to alter initial and preliminary results of early stage clinical
trials; the unpredictability of the duration and results of the
regulatory review of Investigational New Drug Applications (NDAs) and
Clinical Trial Applications that are necessary to continue to advance
and progress the Company’s clinical programs and the regulatory review
of NDAs; market acceptance for approved products and innovative
therapeutic treatments; competition; the possible impairment of,
inability to obtain and costs of obtaining intellectual property rights;
and possible safety or efficacy concerns that could emerge as new data
are generated in research and development, general business, financial
and accounting risks and litigation. The forward-looking statements
contained in this press release reflect Dicerna’s current views with
respect to future events, and Dicerna does not undertake and
specifically disclaims any obligation to update any forward-looking
statements.

Dicerna™, GalXC™, and PHYOX™ are trademarks of Dicerna Pharmaceuticals,
Inc.

Contacts

Investors:
Stern Investor Relations, Inc.
Kendra Packard,
212-698-8688
[email protected]

Media:
SmithSolve
Alex Van Rees, 973-442-1555 ext. 111
[email protected]