Entrada Therapeutics has shared new data from a preclinical study evaluating ENTR-601-44, an exon-skipping therapy set to target individuals with Duchenne amenable to exon 44 skipping.
We are pleased to hear new data on this potential therapeutic and to learn that the company is on track to file an Investigational New Drug (IND) application to the FDA in Q4 2022 in hopes of initiating a clinical trial in participants with Duchenne.
Read the Press Release from Entrada:
Entrada Therapeutics Presents New Data Supporting its Growing Pipeline of Endosomal Escape Vehicle (EEV™) Therapeutics at TIDES USA 2022
New non-human primate data demonstrate a durability of response through 12 weeks for lead clinical candidate, ENTR-601-44, for the potential treatment of Duchenne muscular dystrophy
Second clinical candidate, ENTR-701, announced for the potential treatment of myotonic dystrophy type 1
On track to submit Investigational New Drug applications to the U.S. Food and Drug Administration for ENTR-601-44 targeting Duchenne muscular dystrophy in Q4 2022 and for ENTR-701 targeting myotonic dystrophy type 1 in 2023
BOSTON, May 11, 2022 (GLOBE NEWSWIRE) — Entrada Therapeutics, Inc. (Nasdaq: TRDA), a biopharmaceutical company aiming to transform the lives of patients by establishing intracellular Endosomal Escape Vehicle (EEV™) therapeutics as a new class of medicines, today 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).
“We are proud to present new data at TIDES USA for our lead clinical candidate, ENTR-601-44 for Duchenne muscular dystrophy, and to announce our clinical candidate for myotonic dystrophy type 1 as we continue to expand our pipeline of EEV therapeutics,” said Natarajan Sethuraman, PhD, Chief Scientific Officer of Entrada. “To date, we have generated robust in vitro and in vivo preclinical data supporting the advancement of our DMD and DM1 programs. These encouraging data reinforce the potential of our EEV therapeutic candidates to engage previously inaccessible and undruggable disease-causing targets within cells, and we look forward to presenting additional data at upcoming scientific meetings.”
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 (See Figure 1). 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.
Figure 1: A single IV dose of ENTR-601-44 resulted in robust exon skipping in both skeletal and cardiac muscles in NHP, as well as prolonged duration of effect for at least 12 weeks
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.
About Duchenne Muscular Dystrophy (DMD)
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 Q4 2022.