Translate Bio to Present Preclinical Data Supporting MRT5005 at the 32nd Annual North American Cystic Fibrosis Conference
-- Findings support ongoing Phase 1/2 study of once-weekly nebulized MRT5005 in adults with cystic fibrosis --
“MRT5005 is engineered to deliver mRNA encoding fully functional CFTR protein to the lung epithelial cells through nebulization. These data demonstrate MRT5005’s ability to reach the lungs in animal studies, including in a disease model with increased mucus accumulation, resulting in functional protein expression,” said Dr.
Details of the thematic poster session are as follows:
Poster Title: In Vitro and In Vivo Evaluation of an mRNA Therapeutic (MRT) for the Treatment of Patients with Cystic Fibrosis (CF)
Thematic Poster Session:TPS02--CFTR: Novel Therapeutic Approaches to Treat CFTR Defects
Date and Time:
Abstract number: 281
Dr. Barbier will also present the poster during the NACFC poster session on
Preclinical study data
- Findings will be presented from functional experiments demonstrating the ability of MRT5005 to restore chloride ion channel activity in cells lacking CFTR as well as in a CFTR knockout animal model when compared to control conditions. Importantly, the increase in nasal potential difference observed in the knockout rat model indicate MRT5005 can cross the mucus layer and produce functional human CFTR (hCFTR) protein in nasal epithelia in vivo.
- Additional experiments show robust dose-dependent delivery of codon-optimized hCFTR mRNA with increased levels compared to endogenous CFTR mRNA in both rats (up to 1000-fold) and non-human primates (up to 1500-fold) after a single dose. Subsequent hCFTR protein production was observed by immunohistochemical staining with dose-dependent staining intensity that generally reflected the mRNA levels that were measured. Widespread CFTR protein expression was observed throughout the upper and lower airways after a single dose in both species. Importantly, at the highest doses, the observed levels of mRNA and expressed hCFTR were higher than the normal (endogenous) levels through 28 days after administration by nebulization.
- Successful repeat dosing experiments with MRT5005 was also conducted in rats and non-human primates. After five weekly nebulized treatments with MRT5005, the presence of hCFTR protein was observed 24 hours after the final dose as well as after the 28-day recovery period in both species. MRT5005 was well tolerated with no adverse effects seen in all doses tested.
The full abstract #281 can be found at
MRT5005 is the first clinical-stage mRNA product candidate designed to address the underlying cause of cystic fibrosis (CF) by delivering mRNA encoding fully functional cystic fibrosis transmembrane conductance regulator (CFTR) protein to the lung epithelial cells through nebulization. Once the inhaled MRT5005 has entered the epithelial cells lining the patient’s lungs, the therapeutic mRNA uses the cells’ own machinery for translation and expression of fully functional CFTR protein. This treatment aims to restore the essential ion channel that is defective or absent in patients with CF, addressing the pathology of CF directly regardless of genetic mutation. In 2015, the
About Cystic Fibrosis
Cystic fibrosis (CF) is the most common fatal inherited disease in
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include, but are not limited to, those regarding: the potential for MRT5005 to address the underlying cause of CF, the ability of MRT5005 to deliver mRNA encoding fully functional CFTR protein to the lung and to treat all patients with CF, regardless of the underlying genetic mutation, and the success of Translate Bio’s ongoing Phase 1/2 clinical trial of MRT5005. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from current expectations and beliefs, including but not limited to: Translate Bio’s ability to advance the development of its platform and programs under the timelines it projects, demonstrate the requisite safety and efficacy of its product candidates and replicate in clinical trials any positive findings from preclinical studies; Translate Bio’s ability to enroll patients in its ongoing clinical trial; the content and timing of decisions made by the
Source: Translate Bio, Inc.