ENTR-601-44

Table of contents

• What is ENTR-601-44?
• How does ENTR-601-44 work?
• Which conditions is ENTR-601-44 studied for?
• How is ENTR-601-44 given?
• What do the clinical trials show?
• What side effects are known?

What is ENTR-601-44?

ENTR-601-44 is an investigational substance with no marketing authorisation in the product records.^[1] It is a nucleic acid-based therapy, meaning it is built from nucleic acids rather than being a small chemical molecule or a protein.^[1] The substance is supplied by Entrada Therapeutics, Inc. and appears in the EU trial registry under the product name ENTR-601-44.^[1] A peer-reviewed article describes exon 44 skipping therapies as antisense oligonucleotide (ASO) treatments, a class of RNA-based therapy being explored for Duchenne muscular dystrophy.^[3]

How does ENTR-601-44 work?

ENTR-601-44 is being investigated for Duchenne muscular dystrophy amenable to exon 44 skipping.^[1] In DMD, mutations in the DMD gene disrupt the production of dystrophin, a protein that helps keep muscle cells intact. Antisense oligonucleotide therapies can skip over frame-disrupting exons in the DMD gene and partially restore dystrophin production.^[3] Exon 44 skipping is one such approach, targeting the specific exon 44 region of the gene.^[3] The trial records describe ENTR-601-44 as part of an endosomal escape vehicle phosphorodiamidate morpholino oligomer platform, a delivery technology designed to help the oligonucleotide reach its target.^[2]

Which conditions is ENTR-601-44 studied for?

• Duchenne muscular dystrophy (DMD) — a severe inherited muscle-wasting disorder associated with significant morbidity and mortality.^[3] Both authorised trials of ENTR-601-44 enrol participants with DMD amenable to exon 44 skipping.^[1][2]

How is ENTR-601-44 given?

ENTR-601-44 is formulated as a solution for infusion and is given by intravenous infusion.^[1] In the Phase 2 extension study, the planned dose of ENTR-601-44 is 18 mg/kg given intravenously.^[2]

What do the clinical trials show?

Two authorised trials of ENTR-601-44 are listed in the EU Clinical Trials Information System. The first, ELEVATE-44, is a Phase 1 randomised, double-blind, placebo-controlled study in participants with DMD amenable to exon 44 skipping.^[1] It is planned to enrol 41 participants and compares ENTR-601-44 with a sodium chloride placebo infusion.^[1] The second, ELEVATE-LTE, is a Phase 2 open-label long-term extension study in DMD amenable to exon skipping, with a planned enrolment of 80 participants.^[2] It evaluates ENTR-601-44 at 18 mg/kg and a related product, ENTR-601-45, at 20 mg/kg.^[2]

Both trials measure safety and tolerability as their primary focus. The outcomes include the incidence and severity of treatment-emergent adverse events (TEAEs), changes in vital sign measurements, changes in clinical laboratory results, changes in electrocardiogram (ECG) parameters, and changes in physical examination findings.^[1][2]

What side effects are known?

The peer-reviewed article on exon 44 skipping therapies notes that current DMD treatments are only palliative and that there is a need for more treatment options, but it does not report specific side effects for ENTR-601-44.^[3] The authorised trials are designed to measure safety and tolerability, including treatment-emergent adverse events.^[1][2]