Translate Bio is going to focus on the development of potential therapies to treat pulmonary diseases, including its lead candidate, MRT5005, targeting the underlying cause of cystic fibrosis (CF), the company announced.
MRT5005 is designed to restore the levels of working cystic fibrosis transmembrane conductance regulator (CFTR) protein and reverse the effects of any CF-related genetic mutation. The therapy is formulated to be directly delivered to airway lining cells via nebulization, and it contains the RNA sequence of functional CFTR gene, which will work as a template to produce the protein CF patients are lacking.
MRT5005 was granted orphan drug designation in 2015 by the U.S. Food and Drug Administration for CF treatment.
Translate Bio‘s decision to prioritize pulmonary diseases was based on the improved lung function seen with MRT5005 in the single ascending dose (SAD) part of the ongoing Phase 1/2 RESTORE-CF trial (NCT03375047).
This first part of the study enrolled 12 adult CF patients who received a single administration of MRT5005 at three different doses — 8 mg, 16 mg, or 24 mg. Interim data analysis showed that all patients who received the 16 mg dose, and one treated with the highest 24 mg dose, experienced lung function improvements, as assessed through the increase in the maximal percent predicted forced expiratory volume in one second.
The treatment was well-tolerated, with the most common adverse side effects being cough and headache. No serious treatment-emergent adverse reactions were reported upon treatment with MRT5005.
Translate Bio plans to present full data from this preliminary analysis at the upcoming North American Cystic Fibrosis Conference that will be held Oct. 31–Nov. 2, in Nashville, Tennessee.
Results of the multiple-ascending dose (MAD) portion of the trial, in which participants will be treated once weekly for five weeks with different MRT5005 doses, are expected in 2020. The company is planning to test two new doses (12 and 20 mg) in this second part.
“We believe that the success to date in our cystic fibrosis program positions us well to build on our lung delivery platform and maximize the potential of our mRNA technology in additional pulmonary diseases with unmet medical need,” Ronald Renaud, Translate Bio’s CEO, said in a press release.
Based on unsatisfactory preclinical results, Translate Bio discontinued the development of MRT5201, its therapy candidate intended to treat ornithine transcarbamylase deficiency, a metabolic liver enzyme disorder. Unlike delivery via nebulization in the pulmonary diseases programs, MRT5201 was a lipid nanoparticle (LNP) designed to be given via intravenously.
Despite this setback, Translate Bio continues its search for liver disease mRNA therapies. “We are always evaluating various methods for the delivery of mRNA and we continue to believe that LNPs are currently the most promising technology,” Renaud said, while noting the specific chemical structures and formulations used with LNP to optimize safety and potency.
“We are excited about the robust mRNA delivery effort underway at Translate Bio and we’ll continue to apply our expertise in the development of novel lipids,” he said.