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miRagen Announces Preclinical Safety and Efficacy Data For miR-29 Replacement Product Candidate Intended for the Treatment of Idiopathic Pulmonary Fibrosis

Key Opinion Leader call on IPF scheduled for 11 a.m. ET on Tuesday, June 23rd BOULDER, Colo., June 22, 2020 (GLOBE NEWSWIRE) -- miRagen Therapeutics, Inc. (NASDAQ:MGEN), a clinical-stage biopharmaceutical company

Benzinga · -

Key Opinion Leader call on IPF scheduled for 11 a.m. ET on Tuesday, June 23rd

BOULDER, Colo., June 22, 2020 (GLOBE NEWSWIRE) -- miRagen Therapeutics, Inc. (NASDAQ:MGEN), a clinical-stage biopharmaceutical company focused on the discovery and development of RNA-targeted therapies, today announced preclinical safety and efficacy data for MRG-229, a next-generation miR-29 mimic intended for systemic administration and targeted delivery, in Idiopathic Pulmonary Fibrosis‎ (IPF).


“MRG-229 has demonstrated mechanistic biomarker regulation and antifibrotic activity in vitro using human model systems. In addition, subcutaneous administration of the product candidate induced the reversal of pathologic fibrotic gene expression and resulted in a significant reduction of fibrosis in the most commonly employed pre-clinical animal model of pulmonary fibrosis. Finally, high doses of MRG-229 in preclinical toxicology studies in rats showed no clinically significant toxicity,” stated William S. Marshall, Ph.D., President and Chief Executive Officer of miRagen Therapeutics. “We believe this body of evidence supports further development of MRG-229 as a potentially differentiated approach for the treatment of IPF.”

“In our recently published analysis of fibrosis progression in the human lung, miR-29 emerged as a key regulator of fibrotic pathways in IPF,” said Naftali Kaminski, M.D., Boehringer-Ingelheim Endowed Professor of Internal Medicine, Chief of Pulmonary, Critical Care and Sleep Medicine at Yale School of Medicine, and the principle investigator on NIH-NHLBI CADET grant focusing on mir-29 therapeutics in pulmonary fibrosis. “The most recent data, generated as part of our collaboration with miRagen and supported by an NIH CADET grant, is encouraging and suggests that miR-29 replacement may represent a novel paradigm in the treatment of IPF.”

A summary of the latest preclinical observations:

miR-29 expression was reduced in lungs of IPF patients compared to controls and circulating miR-29 correlates with survival.
Next-generation targeted miR-29 mimics demonstrated target pathway down-regulation assessed by fibrotic gene signatures in normal human lung fibroblasts in vitro. These anti-fibrotic effects extended to collagen secretion, assessed from the cell extract, from diseased lung fibroblasts in vitro, highlighting functional activity in addition to molecular readouts.
Next-generation targeted miR-29 mimics demonstrated efficacy in ex vivo in profibrotic--induced human precision cut lung slices as assessed by histopathology.
Next-generation miR-29 mimics blocked fibrosis in a therapeutic dosing-regimen of mouse bleomycin-induced pulmonary fibrosis with increased potency compared to first generation miR-29 mimics. Anti-fibrotic activity of next-generation miR-29 mimics in mouse bleomycin-induced pulmonary fibrosis was observed for both intravenous and subcutaneous routes of administration.
Potential biomarkers identified in bronchoalveolar lavage fluid and serum for miR-29 antifibrotic activity that could be relevant in future studies.
Preliminary toxicity studies in rats and mice showed MRG-229 showed no clear test article related adverse effects on organ histology, hematology, clinical chemistries, coagulation, or urinalysis when dosed up to 30 mg/kg twice a week for up to 4 weeks. Company believes these data support advancing into Non-Human Primate toxicology studies, which are currently initiating.