Dicerna Reports Potent Preclinical Activity with GalNAc-DsiRNA-EX Conjugates

CAMBRIDGE, Mass.–(BUSINESS WIRE)–Dicerna
Pharmaceuticals, Inc. (NASDAQ:DRNA), a leading developer of
investigational RNA interference (RNAi) therapeutics, today will present
updated preclinical data demonstrating the potency of its proprietary
GalNAc-DsiRNA-EX Conjugate technology in enabling direct delivery of
RNAi-based therapy to the liver via subcutaneous (SC) injection, with
potential utility against multiple therapeutic targets. The presentation
will take place at the 18^th Annual TIDES: Oligonucleotide and
Peptide Research, Technology and Product Development Conference in Long
Beach, Calif.
Bob D. Brown, Ph.D., chief scientific officer and senior vice president
of research at Dicerna, will present an updated case study of the
application of the GalNAc-DsiRNA-EX Conjugate technology to a
well-characterized hepatic disease gene, Alpha-1-antitrypsin (SERPINA1),
resulting in a reduction of serum Alpha-1-antitrypsin (A1AT) in a
transgenic mouse model of liver disease. Dr. Brown will also present
data showing approximately 80% knockdown of SERPINA1 messenger RNA
(mRNA) with a single 3-mg/kg dose of the GalNAc-DsiRNA-EX Conjugate, as
well as approximately 88% knockdown of HAO1, a gene implicated in the
pathogenesis of primary hyperoxaluria type 1 (PH1), a rare, inherited
liver disorder that often results in progressive and severe kidney
damage, at the same 3-mg/kg dose.
“Our proprietary DsiRNA-EX Conjugates exhibit potent in vivo activity
in rodents and monkeys, suggesting utility against multiple therapeutic
targets,” said Dr. Brown. “In addition to facilitating efficient
delivery and gene target knockdown in the liver, the ‘Tetraloop’
configuration of the GalNAc-DsiRNA-EX Conjugates confers the advantages
of potency, stability and ease of chemical modification without loss of
activity. Extensive testing of sequence versus chemical modifications in
vitro and in vivo has enabled efficient design of molecules
by stamping patterns on sequences, which are starting to yield
predictable in vivo performance. Moreover, the platform is
remarkably tolerant of conjugate linker lengths and chemistries,
offering a significant degree of flexibility in conjugate-mediated
delivery to the liver.”
“Our DsiRNA-EX Conjugate platform continues to generate robust
preclinical data supporting development as subcutaneously delivered,
gene-targeted therapies,” commented Douglas Fambrough, Ph.D., president
and chief executive officer of Dicerna. “We look forward to releasing
additional data throughout 2016 showing short- and long-term gene
knockdown in various animal models of liver disease.”
Dicerna has developed investigational DsiRNA-EX Conjugates for
liver-related diseases by attaching N-acetyl galactosamine (GalNAc)
sugars to one or more points on DsiRNA-EX molecules, yielding multiple
proprietary conjugate delivery configurations. The GalNAc sugars
specifically bind to receptors on target cells, leading to
internalization and access to the RNAi machinery within the cells.
Earlier this year, Dr. Brown presented data showing a greater than 75%
reduction in serum A1AT in non-human primates treated with a prototype
SERPINA1 GalNAc-DsiRNA-EX Conjugate, with effects lasting more than
seven weeks after the last of five SC doses. At the TIDES conference in
Long Beach, he reported that the prototype conjugate provided almost six
months of A1AT protein knockdown in monkeys. Dr. Brown also noted that
Dicerna scientists have identified GalNAc-DsiRNA-EX Conjugates with in
vivo half maximal inhibitory concentrations (IC₅₀, the
concentration needed to inhibit a biological or biochemical function by
half) of ≤1.0 mg/kg against multiple targets.
“We have initiated non-human primate studies of our DsiRNA-EX Conjugates
against multiple therapeutic targets with high-potency leads, and plans
are in place for additional programs,” Dr. Brown said. “As we continue
to advance this platform, we hope to benefit from enhanced understanding
of GalNAc conjugate medicinal chemistry, which appears to offer a unique
therapeutic approach to diseases of the liver and other potential
indications.”
Dr. Brown’s presentation will be available at 12:30 p.m. ET on
Wednesday, May 11, 2016 on the Events
& Presentations page in the Investors & Media section of the
Dicerna website.
About Dicerna Pharmaceuticals, Inc.
Dicerna Pharmaceuticals, Inc., is an RNA interference-based
biopharmaceutical company focused on the discovery and development of
innovative treatments for rare, inherited diseases involving the liver,
for other therapeutic areas in which the liver plays a key role, and for
cancers that are genetically defined. The Company is using its
proprietary RNA interference (RNAi) technology platform to build a broad
pipeline in these therapeutic areas. In many cases, Dicerna is pursuing
targets that have historically been difficult to inhibit using
conventional approaches, but where connections between targets and
diseases are well understood and documented. The Company intends to
discover, develop, and commercialize these 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. 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. DsiRNA-EX Conjugate-mediated delivery
technology is in preclinical development, and the process by which a
preclinical technology could potentially lead to an approved product is
long and subject to significant risks and uncertainties. Applicable
risks and uncertainties include those relating to our preclinical and
clinical research and other risks identified under the heading “Risk
Factors” included in our most recent Form 10-K filing and in other
future filings with the 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.