Entrada Therapeutics advances ENTR‑601‑45 in Duchenne muscular dystrophy after DMC supports dose escalation; Cohort 1 data expected mid‑2026.
Written By: Fariha Sameen, PharmD
Reviewed By: Pharmacally Editorial Team
Entrada Therapeutics has cleared a key milestone in its Phase 1/2 ELEVATE-45-201 trial (NCT07038824) of ENTR-601-45 for Duchenne muscular dystrophy (DMD). Following a review of safety and pharmacokinetic (PK) data from eight participants in Cohort 1, who received 5 mg/kg, the independent Data Monitoring Committee (DMC) recommended advancing to Cohort 2 at 10 mg/kg. All Cohort 1 participants have transitioned into the open-label Phase 2 extension, where long-term safety and efficacy will be evaluated.
Exon 45 DMD Remains an Area of High Unmet Need
ENTR-601-45 is being developed for patients with mutations amenable to exon 45 skipping, a subgroup representing approximately 8% of the DMD population. DMD is a rare, progressive neuromuscular disorder caused by mutations in the dystrophin gene, leading to ongoing muscle degeneration, loss of mobility, respiratory decline, and premature mortality. Despite recent advances in exon-skipping therapies, treatment options for patients with exon 45-skipping amenable mutations remain limited.
EEV Platform Targets Intracellular Delivery
The investigational therapy utilizes Entrada’s proprietary Endosomal Escape Vehicle™ (EEV) platform to improve intracellular delivery of oligonucleotides to muscle tissue. Efficient intracellular delivery has remained a longstanding challenge for exon-skipping therapies, and the EEV platform is intended to enhance uptake and distribution within target cells, potentially improving therapeutic activity.
ELEVATE-45-201 Trial Design
ELEVATE-45-201 is a global, randomized, double-blind, placebo-controlled Phase 1/2 study enrolling 24 ambulatory participants aged 4 to 20 years. The trial includes three multiple ascending-dose cohorts, with planned doses ranging from 5 mg/kg to as high as 15 mg/kg.
Participants receive intravenous infusions once every six weeks during the multiple ascending-dose portion of the study. Investigators are evaluating safety, tolerability, pharmacokinetics, pharmacodynamics, dystrophin production, and functional outcomes. Following the initial three-dose treatment period, participants continue treatment in an open-label Phase 2 extension to assess longer-term safety and efficacy.
The six-week dosing interval may offer a practical advantage by reducing treatment burden compared with more frequent dosing schedules used by some currently available exon-skipping therapies.
Advancing Clinical Development
Natarajan Sethuraman, PhD, President of Research and Development at Entrada Therapeutics, said the DMC’s recommendation supports continued clinical advancement of ENTR-601-45 and enables progression to the next planned dose level. He added that the company remains on track to report Cohort 1 safety findings, along with early pharmacokinetic and dystrophin data, in mid-2026.
Entrada expects to report data from Cohort 1 in mid-2026, with results from Cohorts 2 and 3 expected to follow as dose escalation continues. The upcoming safety, pharmacokinetic, and dystrophin data will provide the first clinical assessment of ENTR-601-45 in patients amenable to exon 45 skipping and help inform the program’s future development strategy.
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About the Writer
Fariha Sameen, PharmD (LinkedIn), is a clinical pharmacy professional with hands-on experience in patient counselling, medication review, therapeutic monitoring, and clinical documentation across multiple departments. She has experience identifying and assessing drug-related problems and supporting medication safety practices. Her interests include pharmacovigilance, ADR reporting, clinical research, and medical writing focused on clear, evidence-based communication.