PhaseRx Demonstrates Therapeutic Efficacy of mRNA Therapeutics in Orphan Liver Disease Model

July 15, 2015

Lead Program to Advance into Clinical Development

SEATTLE, WA – PhaseRx, Inc., a leading biotechnology company focused on developing mRNA therapeutics to treat orphan liver diseases, today announced it has demonstrated therapeutic efficacy in an orphan liver disease model and selected a lead program to advance into clinical development.

Through the application of its Hybrid mRNA Delivery System, PhaseRx has demonstrated high-level expression of the luciferase reporter protein specifically in liver hepatocytes in vivo following the intravenous administration of luciferase mRNA. The Hybrid mRNA Delivery System showed highly specific and active delivery of mRNA directly to hepatocytes with minimal uptake in other major organs and tissues.

Utilizing this delivery system, PhaseRx has achieved preclinical proof of concept for its lead program in a well-accepted animal model of a human orphan liver disease. This has been demonstrated through the normalization of two well-validated therapeutic biomarkers. The treatment was well tolerated, with no toxicities associated with both single and multiple dosing regimens. The selected therapeutic indication is a single-gene disorder in the liver for which there are limited treatment options for patients and is associated with severe consequences for patients.

“The PhaseRx Hybrid mRNA Delivery System is designed to overcome a key stumbling block to the delivery of mRNA drugs into cells. It builds upon our highly efficacious and well tolerated SMARTT Polymer Technology® by enabling greater mRNA protection and uptake into hepatocytes. We are pleased to have successfully demonstrated the ability of this innovative system to specifically and actively target delivery of mRNA to hepatocytes and mediate efficacy in preclinical disease models,” said Robert Overell, Ph.D., President and Chief Executive Officer at PhaseRx. “Furthermore, we are excited to advance this technology into clinical development for orphan liver diseases and potentially address a large unmet medical need for patients.”

PhaseRx Hybrid mRNA Delivery System™

PhaseRx’s Hybrid mRNA Delivery System is designed to address the challenges of RNA delivery through protection of the mRNA in the systemic circulation, specifically targeting hepatocytes and by mediating endosome escape and mRNA delivery into cytoplasm. The system has been developed into an industrialized system that provides robust and scalable manufacture, that is well-tolerated and does not induce innate immunity. The system has demonstrated delivery of a wide range of therapeutic mRNAs to the liver including mRNAs to both cytosolic and mitochondrial proteins.

Unmet Medical Need in Orphan Liver Diseases

There are a large number of inherited metabolic diseases of the liver that are caused by single-gene defects. These genetic deficiencies, or inborn errors in metabolism, are orphan diseases that have severe consequences for patients. The few available drug therapies are often palliative and have significant shortcomings. In many cases, the only cure for these diseases is allogeneic liver transplantation.