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."