공시 • May 12
Entrada Therapeutics, Inc. Presents New Data Supporting its Growing Pipeline of Endosomal Escape Vehicle (EEV(TM)) Therapeutics at TIDES USA 2022
Entrada Therapeutics, Inc. presented updates to its two lead programs at TIDES USA 2022: Oligonucleotide & Peptide Therapeutics Conference. The company announced new non-human primate (NHP) data demonstrating durability of response through 12 weeks for ENTR-601-44, an EEV-conjugated phosphorodiamidate morpholino oligomer (PMO) for the potential treatment of people with Duchenne muscular dystrophy (DMD) who are exon 44 skipping amenable. Entrada also announced its second clinical candidate, ENTR-701, an EEV-PMO that the company is developing as a potential allele-specific treatment for people living with myotonic dystrophy type 1 (DM1). The new data from a preclinical study evaluating ENTR-601-44 for the potential treatment of DMD, show robust exon 44 skipping in NHP biceps through 12 weeks following a single intravenous (IV) infusion, demonstrating durability of response. These data build on a previously reported NHP study indicating robust exon 44 skipping across different muscle groups at 7 days following a single IV infusion. The selection of ENTR-701 as Entrada’s clinical candidate for DM1 was supported by new preclinical data indicating prolonged splicing correction in the tibialis anterior, triceps and quadriceps, and amelioration of myotonia in a DM1 mouse model following a single dose.The presentation, entitled “Endosomal Escape Vehicle (EEV)-Conjugation Enhances Functional Delivery of Oligonucleotides,” given by Leo Ziqing Qian, PhD, Co-Founder and Vice President, Discovery Research at Entrada, will be made available on the Publications & Conferences section of the Entrada website following the conference. Duchenne muscular dystrophy is a rare, genetic disease that causes progressive muscle degeneration and weakness throughout the body. DMD is caused by mutations in the DMD gene, which leads to inadequate production of dystrophin, a protein essential to maintaining the structural integrity and function of muscle cells. DMD causes progressive loss of muscle function throughout the body, which limits mobility and causes heart and respiratory complications in the later stages of the disease. Currently approved therapies for DMD seek to improve dystrophin production, but to date, the clinical benefits of these products have not been confirmed. ENTR-601-44, a proprietary Endosomal Escape Vehicle (EEV™)-conjugated phosphorodiamidate morpholino oligomer, is the first novel clinical candidate from Entrada’s growing pipeline of EEV therapeutics. ENTR-601-44 is designed to address the underlying cause of Duchenne muscular dystrophy by skipping the mutated or missing exons in pre-mRNA inherent to DMD. ENTR-601-44 has the potential to restore the mRNA reading frame and allow for the translation of dystrophin protein that is slightly shortened but still functional. Entrada expects to file an IND application with the U.S. FDA for ENTR-601-44 for the potential treatment of patients with Duchenne muscular dystrophy who are amenable to exon 44 skipping in Fourth Quarter 2022. Myotonic dystrophy type 1 is a multi-systemic neuromuscular disease that causes progressive muscle loss and weakness, leading to physical impairment, activity limitations and decreased participation in social activities and work. DM1 is an autosomal dominant disease caused by a mutation to the dystrophia myotonica protein kinase gene, which leads to toxic mRNA that sequesters and reduces function of the muscle blind-like proteins. This causes mis-regulation of multiple RNA splicing events that are correlated with DM1 symptoms, which include muscle weakness, myotonia, cardiac conduction abnormalities, respiratory muscle impairment, gastrointestinal complications and fatigue. DM1 can occur at any age, however, classic disease onset typically occurs in the 20s and 30s and life expectancy can range from 45 to 60 years, with 70% of early mortality caused by cardiac or respiratory complications. There are currently no approved therapies for people living with DM1. Instead, treatment is focused largely on symptom management. ENTR-701, a proprietary Endosomal Escape Vehicle (EEV™)-conjugated phosphorodiamidate morpholino oligomer, is the second novel clinical candidate from Entrada’s growing pipeline of EEV therapeutics. ENTR-701 is designed to address the underlying cause of myotonic dystrophy type 1 through allele-specific targeting and blocking of the excess repeat-containing transcripts in dystrophia myotonica protein kinase mRNA. In doing so, ENTR-701 has the potential to restore the function of muscle blind-like proteins, correct the mis-splicing and aberrant expression of downstream transcripts and restore normal muscle function. Data from preclinical studies of ENTR-701 suggest correction of disease relevant biomarkers in various muscle groups. Entrada expects to file an IND application with the U.S. FDA for ENTR-701 in 2023.