MRT5005 / Sanofi - LARVOL DELTA

Inhaled mRNA therapy for treatment of cystic fibrosis: Interim results of a randomized, double-blind, placebo-controlled phase 1/2 clinical study. (PubMed, J Cyst Fibros) - "MRT5005 was generally safe and well tolerated through 28 days of follow-up after the last dose, though febrile and hypersensitivity reactions were noted. The majority of these reactions resolved within 1-2 days with supportive care allowing continued treatment with MRT5005 and careful monitoring. In this small first-in-human study, FEV1 remained stable after treatment, but no beneficial effects on FEV1 were observed."

Clinical • Journal • P1/2 data • Cough • Cystic Fibrosis • Fibrosis • Gene Therapies • Genetic Disorders • Immunology • Pain • Pulmonary Disease • Respiratory Diseases • CFTR

CAMP4 poaches Translate Bio medical chief, adds ex-Biogen R&D leader Al Sandrock to advisory board (FierceBiotech) - "While at Translate, Barbier led the development of an inhaled messenger RNA therapy for cystic fibrosis. The asset, dubbed MRT5005, experienced mixed results in the clinic and was going through a phase 1/2 trial in the lung disorder. The drug does not appear on Sanofi's pipeline page."

Discontinued • Cystic Fibrosis

[VIRTUAL] A lipid nanoparticle–based delivery system for the treatment of CF (NACFC-I 2021) - "The first such therapeutic (MRT5005) is in clinical testing... Platform developments have allowed optimization of key properties of our LNP-based therapeutics. This work has the potential to be applied beyond CFTR to other inhaled therapeutic mRNAs."

CFTR

[VIRTUAL] Safety and tolerability of single and repeat doses of MRT5005, an inhaled CFTR mRNA replacement therapy, in adult CF patients (NACFC-I 2021) - P1/2 | "Interim results indicate that MRT5005 has an acceptable safety and tolerability profile. Detailed, unblinded safety results, pharma cokinetics, and immunogenicity data from the third interim analysis will be reported for all dose groups, with last patient last visit for this analysis complete this summer. Further development of MRT5005 will be informed by this dataset, as well as ongoing preclinical and translational work of MRT5005 and next-generation drug candidates."

Clinical • Immunology • Pain • Pulmonary Disease • Respiratory Diseases

Translate Bio Announces Second Quarter 2021 Financial Results and Provides Corporate Update (GlobeNewswire) - "mRNA Therapeutics Programs: Generated positive preclinical data for next-generation CF program: Data demonstrates CFTR protein expression in the lungs of animals after the delivery of the next-generation CF product candidate using the intended inhaled route of administration."

Preclinical • Cystic Fibrosis

Safety and tolerability of single and repeat doses of MRT5005, an inhaled CFTR mRNA replacement therapy, in adult CF patients (NACFC 2021) - No abstract available

Clinical

Translate Bio Announces First Quarter 2021 Financial Results and Provides Corporate Update (GlobeNewswire) - "Advanced preclinical pulmonary programs: The Company advanced its next-generation CF and primary ciliary dyskinesia (PCD) programs with positive preclinical data generated to support planned initiation of investigational new drug application (IND)-enabling studies in the second half of 2021...Continue ongoing and additional translational studies with MRT5005 and a next-generation CF candidate to support and optimize future clinical development, including research into dosing, formulation and nebulization."

New trial • Preclinical • Cystic Fibrosis

Why Translate Bio Shares Are Tanking Today (The Motley Fool) - "Shares of Translate Bio (NASDAQ:TBIO) were tanking 31.8% as of 11:26 a.m. EDT on Thursday. The big drop came after the company announced results following the market close on Wednesday from a second interim data analysis of a phase 1/2 study of MRT5005 in treating cystic fibrosis (CF)....Was that no clear improvement was observed in lung function among patients...summed it up in a note to investors by stating, 'the trial failed'....However, the primary focus of the phase 1/2 study was to evaluate the safety and tolerability of MRT5005."

P1/2 data • Stock price • Cystic Fibrosis • Genetic Disorders

Translate Bio Announces Results from Second Interim Data Analysis from Ongoing Phase 1/2 Clinical Trial of MRT5005 in Patients with Cystic Fibrosis (CF) (GlobeNewswire) - P1/2, N=40; RESTORE-CF (NCT03375047); Sponsor: Translate Bio; "In evaluating safety and tolerability, the primary outcome measure, repeat dosing of MRT5005 was generally safe and well tolerated with no serious adverse events; treatment-emergent adverse events (TEAEs) were mild to moderate; transient, mild to moderate symptoms of a febrile reaction such as fever, headache and chills occurred in three patients after the first dose of MRT5005 and did not recur with subsequent dosing in the two patients who continued dosing; the third patient discontinued due to the febrile reaction. Percent predicted forced expiratory volume in 1 second (ppFEV1), a measure of lung function, was assessed as a safety measure at pre-defined timepoints throughout the trial; there was no pattern of increases in ppFEV1."

P1/2 data • Cystic Fibrosis • Genetic Disorders

Translate Bio Announces Timing of Interim Results from mRNA Therapeutic Clinical Trial in Patients with Cystic Fibrosis; Data Expected in Early Q2 2021 (GlobeNewswire) - "Translate Bio...announced today that it has completed enrollment and dosing in the dose cohorts comprising the second interim data analysis from its Phase 1/2 clinical trial for MRT5005 in cystic fibrosis (CF). These include multiple-ascending dose (MAD) groups (8, 12 and 16 mg), and a 20 mg single-ascending dose (SAD) group. The Company anticipates reporting interim clinical data from these cohorts early in the second quarter of 2021."

P1/2 data • Trial status • Cystic Fibrosis • Genetic Disorders

Translate Bio Announces Third Quarter 2020 Financial Results and Reviews Recent Progress (GlobeNewswire) - "Preclinical data presented from the next-generation CF program demonstrated that the design of novel mRNA sequences encoding wild-type and rationally engineered CFTR protein produced active ion channels and enhanced protein expression when compared to reference experiments in vitro. Preclinical studies are ongoing to select the optimal mRNA sequence and LNP for the Company’s next-generation CFTR product candidate."

Preclinical • Cystic Fibrosis

Translate Bio Highlights mRNA Platform Potential for the Treatment of Cystic Fibrosis (CF) at the 34th Annual North American Cystic Fibrosis Conference (GlobeNewswire) - "In an oral presentation entitled, 'Delivering CFTR mRNA: An Inhaled, Mutation-agnostic Approach to Treat CF,' the Company discusses the potential of nucleic acid therapies to treat the underlying cause of cystic fibrosis (CF), particularly through the promise of messenger RNA (mRNA) therapeutics. The presentation underscores the remaining unmet need in treating CF and provides an overview of the development of its lead clinical candidate, MRT5005, currently being evaluated in a Phase 1/2 clinical trial in people with CF."

Clinical data • Cystic Fibrosis • Genetic Disorders

[VIRTUAL] DESIGN OF NEXT GENERATION CFTR MRNA THERAPEUTICS FOR THE TREATMENT OF PATIENTS WITH CYSTIC FIBROSIS (NACFC 2020) - "A clinical study with the first inhaled mRNA therapeutic, MRT5005, yielded encouraging initial data, and additional innovations to optimize the overall drug candidate profile of successive therapeutics are being explored... Design of novel mRNA sequences encoding rationally engineered CFTR protein was shown to produce highly active ion channels and significant protein expression when compared to a reference sequence encoding the native protein. These novel constructs, when combined with efficient delivery systems such as lipid nanoparticles, possess the potential to deliver a potent messenger RNA therapeutic for treatment of patients with cystic fibrosis, regardless of underlying mutation."

Clinical • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Respiratory Diseases

Translate Bio Resumes Enrollment and Dosing in Phase 1/2 Clinical Trial of MRT5005 in Cystic Fibrosis (GlobeNewswire) - "Translate Bio...today announced that enrollment and dosing in its Phase 1/2 clinical trial for MRT5005 in cystic fibrosis (CF) has resumed, with multiple clinical sites being open for enrollment...The Company plans to provide updated timing on the expected interim data readout of the additional single-ascending dose (SAD) group and the multiple-ascending dose (MAD) portion of the clinical trial at a later date."

Enrollment status • Cystic Fibrosis

Translate Bio provides MRT5005 program updates (GlobeNewswire) - “Translate Bio...today announced two updates related to its MRT5005 clinical development program in cystic fibrosis (CF). First, the U.S. Food and Drug Administration (FDA) has granted Rare Pediatric Disease (RPD) designation for MRT5005 for the treatment of CF….The Company anticipates related interruptions in enrollment, dosing and follow-up in the ongoing Phase 1/2 clinical trial in patients with CF. The Company plans to provide updated timing on the expected interim data readout of the additional single-ascending dose (SAD) group and the multiple-ascending dose (MAD) portion of the clinical trial at a later date.”

Enrollment status • P1/2 data • Cystic Fibrosis

"$TBIO FDA grants Rare Pediatric Disease designation for MRT5005 for treatment of cystic fibrosis" (@BioStocks)

Clinical

RESTORE-CF: Study to Evaluate the Safety & Tolerability of MRT5005 Administered by Nebulization in Adults With Cystic Fibrosis (clinicaltrials.gov) - P1/2; N=40; Recruiting; Sponsor: Translate Bio, Inc.; Trial completion date: Feb 2021 ➔ Dec 2021; Trial primary completion date: Jan 2021 ➔ Oct 2021

Trial completion date • Trial primary completion date

Translate Bio announces pipeline program update (GlobeNewswire) - "The Company’s prioritization of pulmonary diseases is supported by the previously reported positive single-ascending dose Phase 1/2 data from the CF program, which utilizes its proprietary lung delivery platform. MRT5005 is a first-in-class mRNA therapeutic designed to address the underlying cause of CF regardless of genetic mutation by delivering mRNA encoding fully functional cystic fibrosis transmembrane conductance regulator (CFTR) protein to cells in the lung through nebulization. The multiple-ascending dose portion of the clinical trial is ongoing with data expected in 2020."

P1/2 data

Translate Bio announces fourth quarter and full year 2018 financial results and reviews recent highlights (Nasdaq) - "In 2019, we are continuing to advance the Phase 1/2 clinical trial for MRT5005 in patients with cystic fibrosis for which we anticipate interim data in the second half of the year….Fourth Quarter 2018 and Recent Updates...Translate Bio initiated dosing of patients in the MAD portion of the ongoing first-in-human clinical trial of MRT5005."

P1/2 data • Trial status

Translate Bio Provides Updates on Cystic Fibrosis (CF) and Ornithine Transcarbamylase (OTC) Deficiency Programs (GlobeNewswire, Translate Bio, Inc.) - “Initiated multiple-ascending dose portion of the Phase 1/2 clinical trial of MRT5005 in patients with cystic fibrosis…The Company remains on track to report interim data from the clinical trial in the second half of 2019.”

P1/2 data • Trial status