Entrada Reports Early Functional Benefit in Phase 1/2 Duchenne Study of ENTR-601-44

Entrada Therapeutics has reported positive topline results from Cohort 1 of its ongoing Phase 1/2 ELEVATE-44-201 study evaluating ENTR-601-44 in patients with Duchenne muscular dystrophy (DMD) amenable to exon 44 skipping. The data demonstrated favorable safety and tolerability alongside early signs of functional improvement and dystrophin restoration, supporting continued dose escalation in the study.¹

The clinical-stage biotechnology company said all treatment-emergent adverse events were mild to moderate, with no serious adverse events, treatment discontinuations, or clinically meaningful kidney safety findings observed during the trial. Biomarkers including estimated glomerular filtration rate, Cystatin C, and magnesium remained within normal ranges and comparable to placebo-treated participants.¹

Early Functional Signals Observed

The multiple ascending dose portion of the study enrolled ambulatory DMD patients between four and 20 years old with mutations amenable to exon 44 skipping. In Cohort 1, participants received three intravenous doses of 6 mg/kg ENTR-601-44 or placebo over approximately 12 weeks.

According to the company, treated participants demonstrated a 2.36% increase in dystrophin expression over a 4.00% baseline and a 2.31% increase in exon skipping over a 2.66% baseline. Although the absolute dystrophin increase was modest compared with some exon-skipping programs, Entrada emphasized that the cohort consisted of relatively young participants with low baseline dystrophin levels, a factor that can influence treatment response.

Notably, the company also reported statistically significant improvement in Time to Rise (TTR) velocity compared with placebo, a functional endpoint commonly used to assess disease progression in Duchenne. Entrada stated the improvement exceeded the minimal clinically important difference threshold by approximately 3.5-fold.¹

“The topline results from Cohort 1 of the ELEVATE-44-201 study are promising,” said Laurent Servais, MD, professor of pediatric neuromuscular diseases at the University of Oxford and principal investigator of the study, in the company announcement. “Individuals with Duchenne are in urgent need of new treatments that can provide functional improvements while also offering a more targeted treatment option.”¹

Pharmacokinetic Findings Shape Next Steps

Entrada said the study also revealed lower-than-expected plasma exposure in pediatric DMD participants compared with healthy adult volunteers. The company noted that the pharmacokinetic findings aligned with recently generated juvenile nonhuman primate data, prompting updated exposure modeling for future cohorts.

Based on those findings, Entrada has initiated dosing in Cohort 2 at an increased dose of 12 mg/kg and expects higher plasma exposure and potentially greater dystrophin production. Additional data from Cohort 2 and the open-label extension portion of Cohort 1 are expected by the end of 2026.

Company executives suggested the observed functional improvements may support differentiation within the increasingly competitive exon-skipping landscape.

“We believe we have a highly differentiated delivery mechanism, including the ability to access quiescent satellite cells,” said Natarajan Sethuraman, PhD, president of R&D at Entrada Therapeutics, in the release. “Access to satellite cells enables the repair of existing muscle fibers and importantly, the formation of new healthy fibers.”¹

Growing Competition in Exon-Skipping Therapies

DMD remains an active area of neuromuscular drug development, particularly in exon-skipping therapies designed to restore partial dystrophin production. Several approved therapies target exon 51 skipping, while developers continue advancing programs for additional exon targets, including exon 44.

Exon-skipping therapies use antisense oligonucleotides to modify pre-mRNA splicing and enable production of shortened but functional dystrophin protein.² Longitudinal studies of earlier exon-skipping agents have also highlighted the importance of functional endpoints such as ambulation and motor performance measures when evaluating clinical benefit in Duchenne muscular dystrophy.³

Entrada’s ENTR-601-44 uses the company’s proprietary Endosomal Escape Vehicle technology designed to improve intracellular delivery of oligonucleotide therapies. The therapy received Rare Pediatric Disease Designation from FDA in December 2025.

References

1. Entrada Therapeutics. (2026, May 7). Entrada Therapeutics announces positive topline results from Cohort 1 of participants with Duchenne muscular dystrophy treated with ENTR-601-44 in Phase 1/2 ELEVATE-44-201 study. GlobeNewswire. https://www.globenewswire.com/news-release/2026/05/07/3289797/0/en/entrada-therapeutics-announces-positive-topline-results-from-cohort-1-of-participants-with-duchenne-muscular-dystrophy-treated-with-entr-601-44-in-phase-1-2-elevate-44-201-study.html
   
2. Lim, K. R. Q., Maruyama, R., & Yokota, T. (2017 Feb 28). Eteplirsen in the treatment of Duchenne muscular dystrophy. Drug Design, Development and Therapy. https://doi.org/10.2147/DDDT.S97635
   
3. Mendell, J. R., Goemans, N., Lowes, L. P., Alfano, L. N., Berry, K., Shao, J., ... & Mercuri, E. (2015 Nov 17). Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy. Annals of Neurology. https://doi.org/10.1002/ana.24555