Dicerna Receives Recommendation from EMA Committee to Designate DCR-PHXC an Orphan Medicinal Product for the Treatment of Primary Hyperoxaluria (PH) in the EU

Pharmaceuticals, Inc. (Nasdaq: DRNA), a leading developer of
investigational ribonucleic acid interference (RNAi) therapeutics, today
announced that the European Medicines Agency’s (EMA) Committee for
Orphan Medicinal Products (COMP) has recommended designating DCR-PHXC,
the Company’s lead GalXC™ product candidate, as an orphan medicinal
product for the treatment of primary hyperoxaluria (PH) in the European
Union (EU). The European Commission (EC) is expected to review the COMP
opinion and issue a final ruling within 30 days of receipt. Separately,
Dicerna recently announced that the U.S. Food and Drug Administration
(FDA) granted Orphan Drug Designation to DCR-PHXC for the treatment of

Dicerna is investigating DCR-PHXC for the treatment of all forms of PH,
a family of severe, rare, inherited disorders of the liver that often
result in kidney failure. The Company initiated the PHYOX Phase 1
clinical trial of DCR-PHXC in normal healthy volunteers in the fourth
quarter of 2017 and dosed the first patient with PH in May 2018, with
clinical proof-of-concept data anticipated in the second half of 2018.

“We are gratified to see regulators recognize the urgent need for a safe
and effective therapy for primary hyperoxaluria, as well as the
encouraging preclinical data for DCR-PHXC in various mouse models of
PH,” said Ralf Rosskamp, M.D., chief medical officer of Dicerna. “This
positive recommendation, as well as the Orphan Drug Designation from the
FDA, acknowledges the needs of this underserved patient population.”

The EMA grants orphan medicinal product designation to investigational
drugs intended to treat, prevent or diagnose a life-threatening or
chronically debilitating disease affecting fewer than five in 10,000
people in the EU, and for which no satisfactory treatment is available.
Orphan medicinal product designation provides regulatory and financial
incentives for companies to develop and market therapies, including
market exclusivity, protocol assistance, fee reductions, and EU-funded

In examining the orphan medicinal product application for DCR-PHXC, the
COMP concluded that Dicerna established the following:


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 GalXCTM 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 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 might 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
organ systems 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 idiopathic PH (IPH) or “no mutation
detected” (NMD) PH. 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

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 U.S. and EU 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 (ESRD) 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 diseases involving the liver, including rare
diseases, viral infectious diseases, chronic liver diseases, and
cardiovascular 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. For more
information, please visit www.dicerna.com.

Cautionary Note on Forward-Looking Statements

This press release includes forward-looking statements, including, for
example, Dicerna’s expected timeline and plans for development of
DCR-PHXC, as well as expected regulatory results and timing. Such
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. Applicable risks and uncertainties include
those relating to Dicerna’s clinical and preclinical research and others
identified under the heading “Risk Factors” included in the Company’s
filings with the Securities and Exchanges Commission (SEC). 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.


Oxalosis & Hyperoxaluria Foundation. Overview of hyperoxaluria.
2017. Available at: https://ohf.org/overview/.
Accessed July 6, 2017.

Rare Kidney Stone Consortium. Primary hyperoxaluria. 2010.
Available at: http://www.rarekidneystones.org/hyperoxaluria/physicians.html.
Accessed July 6, 2017.

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