BOSTON, October 14, 2026
Entrada Therapeutics, Inc. (Nasdaq: TRDA) announced positive topline results from Cohort 1 of its Phase 1/2 ELEVATE-45-201 clinical study, evaluating investigational therapy ENTR-601-45 in ambulatory participants with Duchenne muscular dystrophy (DMD) amenable to exon 45 skipping. The initial cohort met its primary objectives for safety and tolerability at the 5 mg/kg dose. Secondary assessments showed a mean increase of 0.10% in dystrophin production and a 0.15% increase in exon skipping from baseline among treated participants. The findings support continued dose escalation, with Cohort 2 enrollment complete and dosing at 10 mg/kg underway. The company expects to report Cohort 2 results in the first half of 2027.
Cohort 1 Meets Primary Safety and Tolerability Objectives
Cohort 1 enrolled eight participants who were randomized in a 3:1 ratio to receive intravenous ENTR-601-45 at 5 mg/kg or placebo. Participants received three doses on Days 1, 43 and 85 as part of the double-blind, placebo-controlled multiple ascending dose portion of the study. The most frequently reported treatment-emergent adverse event was headache, with five events recorded in two participants. One participant experienced two serious treatment-emergent adverse events, vomiting and fever, both of which subsequently resolved. No participants discontinued the study, and all enrolled in the open-label extension. The company also reported no hypomagnesemia or renal safety concerns. Kidney-function markers, including estimated glomerular filtration rate (eGFR) and cystatin C, remained within normal ranges in treated participants, as did magnesium levels. Plasma exposure to ENTR-601-45 was consistent with predictions based on juvenile non-human primate data. These initial findings provide safety and pharmacokinetic information to support further evaluation, although larger cohorts and longer follow-up will be needed to characterize the therapy’s safety profile.
Dystrophin Production and Exon Skipping Show Early Changes
Secondary assessments demonstrated changes in dystrophin production and exon skipping among participants receiving ENTR-601-45. Treated participants showed a mean 0.10% increase in dystrophin from baseline (n=6; nominal p=0.03), compared with a mean 0.02% decrease in the placebo group. Mean exon skipping increased by 0.15% from baseline in treated participants (n=5), while the placebo group experienced a mean decrease of 0.04%. No p-value was calculated for the exon-skipping result. The company noted that dystrophin measurements included observed values below the assay’s lower limit of quantification. Given the participants’ ages, baseline functional status and the limited number of doses administered, no observable functional benefit was expected or detected after the initial three-dose period. Functional outcomes will be assessed during longer treatment periods and in subsequent cohorts. Entrada expects higher doses to produce greater drug exposure and potentially increased dystrophin expression, but these expectations remain to be confirmed by clinical data. All Cohort 1 participants have transitioned to the open-label Phase 2 portion, where they are scheduled to receive six doses of ENTR-601-45 at 5 mg/kg.
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Dose Escalation to Continue in ELEVATE-45-201
ENTR-601-45 is an investigational oligonucleotide conjugated to Entrada’s proprietary Endosomal Escape Vehicle (EEV™) technology. Its sequence is designed for people with confirmed DMD gene mutations amenable to exon 45 skipping. The treatment aims to restore the messenger RNA reading frame, potentially enabling production of a shortened but functional dystrophin protein. The exon 45-skipping population represents approximately 9% of people with Duchenne muscular dystrophy globally, according to the company. ELEVATE-45-201 is a global, two-part Phase 1/2 study evaluating safety, pharmacokinetics, pharmacodynamics and functional parameters in ambulatory participants aged four to 20 years. Cohort 2, evaluating 10 mg/kg, has completed enrollment, and dosing is ongoing; results are expected in the first half of 2027. Cohort 3 is planned to evaluate doses up to 15 mg/kg, subject to the study’s progression and safety assessments. Entrada has highlighted a potential once-every-six-weeks dosing schedule, which could reduce administration frequency compared with weekly treatment regimens. Whether this schedule, higher doses or observed biomarker changes translate into meaningful functional benefits will require further investigation. Duchenne muscular dystrophy is a progressive genetic disease characterized by insufficient dystrophin production, leading to worsening muscle weakness and potentially serious cardiac and respiratory complications. Entrada is developing genetic medicines for neuromuscular and inherited retinal diseases, including programs targeting several DMD exon-skipping populations.
Source::Entrada Therapeutics press release
