Translate Bio has reported positive interim data from a Phase I/II clinical trial of its mRNA candidate MRT5005 for the treatment of cystic fibrosis (CF) patients.

Developed to target the disease’s underlying cause, MRT5005 delivers mRNA that encodes fully functional cystic fibrosis transmembrane conductance regulator (CFTR) protein to lung cells.

The drug candidate, formulated for nebulisation, is not dependent on the patient’s underlying genetic mutation.

In the single ascending dose (SAD) portion of the safety and efficacy trial, 12 patients received an 8mg, 16mg, or 24mg dose of MRT5005 and were followed for one-month after the treatment period.

The product was found to be generally well-tolerated at low and mid-dose levels, without any serious adverse events with any dose. The most common adverse events up to day 29 of the study were cough and headache.

All treatment-emergent adverse events (TEAEs) were observed to be mild to moderate, and no treatment-emergent serious adverse events (SAEs) have been reported.

Analysis for primary lung function measure, ppFEV1, revealed no marked improvements in the pooled 8mg dose and placebo arms.

Three patients treated with the 16mg dose showed maximal ppFEV1 elevations of 11.1%, 13.6%, and 22.2%, for a mean maximum increase from 15.7% baseline in the eight-day period post-dosing.

Of these three patients, two received a stable CFTR modulator therapy for a minimum of 28 days, while the third had a genotype that could not be addressed with the CFTR modulator treatment.

One participant on the 24mg dose of MRT5005 reached a maximum increase in ppFEV1 from baseline of 21.4% and two patients did not achieve a marked increase.

Translate Bio CEO Ronald Renaud said: “These encouraging interim results represent a milestone in the mRNA development landscape as this is the first time an mRNA therapeutic has been evaluated for its potential to treat a genetic disease.”

Based on these findings, the company intends to evaluate a 20mg dose in the SAD portion.

The multiple ascending dose (MAD) portion of the trial is ongoing and will see amendments to include 12mg and 20mg cohorts. This portion will not involve a 24mg cohort.

All new cohorts will enrol four patients each. Top-line data from the 20mg SAD and the MAD portion is expected to be reported next year.