ENTR-601-45

Table of contents

• What is ENTR-601-45?
• How does ENTR-601-45 work?
• Which conditions is ENTR-601-45 studied for?
• How is ENTR-601-45 given?
• What do the clinical trials show?
• What side effects are known?

What is ENTR-601-45?

ENTR-601-45 is an investigational nucleic acid-based substance developed by Entrada Therapeutics, Inc. It is being studied for Duchenne muscular dystrophy (DMD) in people whose genetic mutation is amenable to exon 45 skipping.^[1] The substance is classified in the therapeutic area of musculoskeletal diseases.^[2] ENTR-601-45 has no marketing authorisation in the product records, meaning it has not been approved as a medicine.^[1] It is part of a platform of endosomal escape vehicle phosphorodiamidate morpholino oligomer products, a type of exon-skipping therapy.^[2]

How does ENTR-601-45 work?

ENTR-601-45 is designed to increase dystrophin protein production in muscles. Dystrophin is a protein that helps muscles function properly, and people with Duchenne muscular dystrophy have little or no functional dystrophin.^[3] The therapy uses exon skipping, a technique that allows the body to produce a shorter but still functional version of the dystrophin protein. ENTR-601-45 specifically targets exon 45 of the dystrophin gene, making it suitable only for people whose mutation can be addressed by skipping this exon.^[3]

Which conditions is ENTR-601-45 studied for?

• Duchenne muscular dystrophy — a genetic muscle-wasting condition that mainly affects boys and leads to progressive muscle weakness. ENTR-601-45 is being studied only in people whose DMD mutation is amenable to exon 45 skipping.^[1][2]

How is ENTR-601-45 given?

ENTR-601-45 is given as a solution for infusion by intravenous infusion.^[1] In the long-term extension study, the dose of ENTR-601-45 is reported as 20 mg per kilogram of body weight.^[2] The trial records also list sodium chloride as an intravenous infusion, which serves as the placebo or comparison arm in the randomised study.^[1]

What do the clinical trials show?

Two authorised trials of ENTR-601-45 are listed in the EU Clinical Trials Information System. One trial is a Phase 1/2 randomised, double-blind, placebo-controlled study called ELEVATE-45, with 38 planned participants.^[1] The second is a Phase 2 open-label long-term extension study called ELEVATE-LTE, with 80 planned participants.^[2] Both studies are interventional and focus on safety and tolerability as their primary outcomes. The ELEVATE-45 study has two parts: Part A assesses safety, tolerability, pharmacokinetics (how the drug moves through the body) and pharmacodynamics (how the drug affects the body), while Part B evaluates safety and efficacy. Participants in Part A of ELEVATE-45 have a 75% chance of receiving ENTR-601-45 and a 25% chance of receiving placebo.^[3] Both trials measure treatment-emergent adverse events, vital signs, clinical laboratory results, electrocardiogram (ECG) parameters and physical examination findings as primary outcomes.^[1][2]

What side effects are known?

The trials are designed to identify side effects, and the primary outcomes include the incidence and severity of treatment-emergent adverse events.^[1][2] The research summary states that the study aims to identify any side effects of ENTR-601-45.^[3] No specific side effects have been reported in the available sources, as the trials are still in early phases and results have not been published.