MDRNA, Inc. announced
today that it has advanced its RNAi pipeline with the selection of a Lead Candidate
in its hypercholesterolemia program targeting Apolipoprotein B (ApoB). The compound,
designated MDR-04227, was developed using MDRNA's propriety drug discovery engine,
which is built on a broad and enabling intellectual property estate and an in-house
novel and proprietary delivery technology.
"We continue to execute on our plan to advance our therapeutic programs
toward human clinical development," stated J. Michael French, President
and CEO of MDRNA, Inc. "The selection of a Lead Candidate in our hypercholesterolemia
program reflects the strength of our drug discovery engine, specifically the
rapid advances we've made in siRNA delivery. Further, I believe the speed and
efficiency by which we can develop a lead candidate demonstrates our ability
to utilize this drug discovery platform to support a broad therapeutic collaboration
with a pharmaceutical partner. MDRNA's unique combination of technology, in-house
capability and intellectual property portfolio permits us to broadly support
a potential partner's needs and develop siRNAs directed against any human gene
target."
MDR-04227 is a Dicer substrate siRNA formulated with a proprietary lipid-based
delivery formulation derived from the Company's DiLA2 Platform. In a preclinical
animal model of hypercholesterolemia, MDR-04227 was shown to be extremely potent
with an IC50 of less than 100 pM. When formulated for systemic administration
using DiLA2, MDR-04227 demonstrated approximately 85% knockdown in target messenger
RNA of ApoB and a similar level of reduction of serum cholesterol following
a single 1 mg/kg dose of siRNA. The Company has filed numerous patent applications
relating to this siRNA construct and delivery formulation.
"Our lead selection process, whose multifaceted criteria include potency,
cytokine induction, on-target specificity and resistance to nuclear degradation,
has led to the selection of MDR-04227," commented Steven C. Quay, M.D.,
Ph.D., Chairman of the Board of Directors and Chief Scientific Officer. "MDR-04227
is formulated in our DiLA2 delivery technology and optimized for systemic delivery
to the liver and gastrointestinal tract. The percentage of ApoB knockdown and
reduction of serum cholesterol achieved in our animal model appears to exceed
data in the published literature in which effects of this magnitude required
doses of more than 2 mg/kg and often up to 5 mg/kg siRNA. We believe these results
are a testament to the high potency of our Dicer substrate siRNAs as well as
the robustness of the DiLA2 delivery platform."