miRagen to Refocus on Development of Potential IPF Therapy MRG-229

Ana Pena, PhD avatar

by Ana Pena, PhD |

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miRagen Therapeutics is reshaping its strategy to focus on the development of MRG-229, a potential treatment for idiopathic pulmonary fibrosis (IPF).

The company expects to share new efficacy and safety preclinical data on MRG-229 during the first half of 2020.

MRG-229 is a second-generation mimic of miR-29, a microRNA naturally produced in our body. MicroRNAs are small RNA molecules that are able to “turn off” specific genes; that is, to block the ability of certain genes to instruct the making of proteins.

miR-29 is specifically found at abnormally low levels in patients with different types of fibrosis (scarring), including in the lungs of people with IPF. The low levels of miR-29 are thought to contribute to the accumulation of scar tissue.

There is evidence that miR-29 exerts an important anti-fibrotic activity, preventing key processes involved in fibrosis from happening, such as the accumulation of extracellular matrix — a mesh of proteins and sugars that gives support to tissues — and the release of profibrotic and inflammatory molecules such as transforming growth factor-beta (TGF-β).

The rationale behind agents that mirror the mode of action of miR-29 — such as MRG-229 — is that they are able to replace it and overcome its insufficient levels, helping prevent fibrosis.

Based on promising preclinical data, miRagen believes that MRG-229’s efficacy and safety speak to its potential as a treatment for IPF. Encouraged by these results, the company decided to reorient its pipeline strategy and future resources primarily to the development program of MRG-229.

This program is supported by the National Institutes of Health and Yale University.  

“We are executing on a strategy to streamline our operations, which we believe will allow us to focus our development efforts and deliver important milestones in 2020,” William S. Marshall, PhD, president and CEO of miRagen, said in a press release.

“We have … been encouraged by the preclinical data we have generated with our next generation microRNA-29 mimic, MRG-229, and will primarily focus our pipeline development efforts and allocation of future capital on advancing MRG-229,” Marshall said.

According to its CEO, miRagen believes that the preclinical data obtained so far with MRG-229 shows its “potential for superior efficacy in treating patients with IPF. If effective, MRG-229 possesses a mechanism of action that we believe could be particularly valuable for patients with this deadly disease,” Marshall said.

Another mimic of miR-29, called remlarsen, started its development earlier and is miRagen’s most advanced candidate for the treatment of fibrosis, specifically for keloids — excessive growths of scar tissue in the skin.

Remlarsen is currently being tested in a Phase 2 trial (NCT03601052) evaluating its safety and efficacy in the prevention or treatment of keloids. Preliminary data from this study suggest that remlarsen is generally safe, and appears to lower scar tissue formation in some patients compared to placebo.

Based on these early findings, miRagen decided to proceed with the trial analysis, and may seek additional collaborators to pursue the development of remlarsen, along with the MRG-229 program.