Demonstrates RNAi-Mediated Knockdown of Previously "Non-Druggable" Targets in Liver and Bladder Cancers
BOTHELL, WA--(Marketwire - October 12, 2009) - MDRNA, Inc. (NASDAQ: MRNA), a leading
RNAi-based drug discovery and development company, today presented new in
vivo data demonstrating continued progress in the advancement of the
Company's oncology program. J. Michael French, President and CEO, reported
that MDRNA's UsiRNAs, delivered by the Company's DiLA2 platform,
down-regulated a previously "non-druggable" target with subsequent
reductions in tumor growth in models of liver and bladder cancer via both
systemic and local delivery.
In a presentation to BioPartnering Europe in London today, Mr. French said
that MDRNA has demonstrated successful delivery of a UsiRNA targeting
survivin, a protein involved in mitotic progression and inhibition of
apoptosis, via intravenous administration using its DiLA2 liposome
formulation in two liver cancer models. Knockdown ( > 60%) of survivin mRNA
in a rodent orthotopic model was noted as early as 24 hours after a second
(of six) dose and this was associated with an approximate 65% decrease in
tumor weight at study termination; this decrease was comparable to tumor
weight reduction with Avastin® (bevacizumab)-treated mice as a positive
control. A similar level of survivin mRNA knockdown was noted in
subcutaneously implanted liver tumors following intravenous administration
of the UsiRNA/DiLA2 liposomes.
Data from an orthotopic bladder cancer model were also presented, in which
localized application (intravesical dosing) of the survivin UsiRNA to a
bladder tumor was performed using a DiLA2 liposome formulation. Again, the
UsiRNA was highly active in providing gene silencing, demonstrating > 90%
inhibition of survivin mRNA which was dose-dependent and sustained over at
least a three week period. At study termination there was also a
dose-dependent decrease in bioluminescence of up to approximately 90% in
UsiRNA-treated mice which is a clear indication of reduced tumor growth.
Mr. French said, "We have always maintained that our RNAi discovery engine
can generate novel compounds with broad therapeutic applicability. These
data are a powerful indicator of the value and strength of that drug
discovery platform and represents a significant step in the advancement of
our product pipeline. Moreover, we now have evidence illustrating the
potential role of RNAi-based therapeutics in down-regulating typically
'non-druggable' targets."
The presentation given by Mr. French is posted on the Company website
(www.mdrnainc.com).
About UsiRNAs
A UsiRNA is a duplex siRNA containing at least one Unlocked Nucleobase
Analog (UNA). In a UsiRNA, UNAs are non-nucleotide monomers and
synthesized much like RNA in the construction of a double-stranded
oligonucelotide for use as an RNAi-based therapeutic. In the case of the
UsiRNA, UNA is substituted for specific nucleotides in both the guide and
passenger strands. UsiRNAs are fully recognized by the cellular RNAi
machinery, as demonstrated by their potent activity. MDRNA has also shown
that substitution of UNA for specific RNA increases stability to nucleases,
substantially reduces cytokine induction, and reduces passenger and guide
strand-mediated offtarget effects. The high potency, and improved drug-like
properties, associated with UsiRNAs provide the potential to greatly
enhance RNAi-based therapeutics.
About the DiLA2 Delivery Platform
The DiLA2 Delivery Platform is MDRNA's proprietary platform for creating
novel liposomal delivery systems based on di-alkylated amino acids (DiLA2).
The DiLA2 Platform enables MDRNA to tailor the charge, linker length, and
acyl chain characteristics to improve delivery of the liposomes to target
tissue of interest. In vivo studies have demonstrated effective delivery in
models of metabolic disease, cancer, and other diseases. DiLA2-based
liposomes are well tolerated for repeat dose, and systemic and local
administration. MDRNA is also utilizing condensing peptides to form
peptide-siRNA nanoparticles to further increase the delivery efficiency of
its DiLA2 delivery systems. In addition, the platform is designed to permit
attachment of peptides and other targeting molecules for delivery to a
variety of tissues, and thus provide for a diverse therapeutic portfolio.
About MDRNA, Inc.
MDRNA is a biotechnology company focused on the development and
commercialization of therapeutic products based on RNA interference (RNAi).
Our goal is to improve human health through the development of RNAi-based
compounds and drug delivery technologies that together provide superior
therapeutic options for patients. Over the past decade, we have developed
substantial capabilities in molecular biology, cellular biology, lipid
chemistry, peptide chemistry, pharmacology and bioinformatics, which we are
applying to a wide range of RNAi technologies and delivery approaches.
These capabilities plus the in-licensing of key RNAi-related intellectual
property have rapidly enabled us to become a leading RNAi-based
therapeutics company with a pre-clinical pipeline in oncology. Through our
capabilities, expertise and know-how, we are incorporating multiple RNAi
technologies as well as peptide- and lipid-based delivery approaches into a
single integrated drug discovery platform that will be the engine for our
clinical pipeline as well as a versatile platform for establishing broad
therapeutic partnerships with biotechnology and pharmaceutical companies.
We are also investing in new technologies that we expect to lead to safer
and more effective RNAi-based therapeutics while aggressively building upon
our broad and extensive intellectual property estate. By combining broad
expertise in siRNA science with proven delivery platforms and a strong IP
position, MDRNA is well positioned as a leading RNAi-based drug discovery
and development company. Additional information about MDRNA, Inc. is
available at http://www.mdrnainc.com.
MDRNA Forward-Looking Statements
Statements made in this news release may be forward-looking statements
within the meaning of Federal Securities laws that are subject to certain
risks and uncertainties and involve factors that may cause actual results
to differ materially from those projected or suggested. Factors that could
cause actual results to differ materially from those in forward-looking
statements include, but are not limited to: (i) the ability of MDRNA to
obtain additional funding; (ii) the ability of MDRNA to attract and/or
maintain manufacturing, research, development and commercialization
partners; (iii) the ability of MDRNA and/or a partner to successfully
complete product research and development, including preclinical and
clinical studies and commercialization; (iv) the ability of MDRNA and/or a
partner to obtain required governmental approvals; and (v) the ability of
MDRNA and/or a partner to develop and commercialize products that can
compete favorably with those of competitors. Additional factors that could
cause actual results to differ materially from those projected or suggested
in any forward-looking statements are contained in MDRNA's most recent
periodic reports on Form 10-K and Form 10-Q that are filed with the
Securities and Exchange Commission. MDRNA assumes no obligation to update
and supplement forward-looking statements because of subsequent events.