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Entrada Therapeutics (NASDAQ: TRDA) said initial data from the first cohort of its phase I/II ELEVATE-44-201 trial showed favorable safety and tolerability and early functional improvement in ambulatory Duchenne muscular dystrophy (DMD) patients with mutations amenable to exon 44 skipping.
The company reviewed the results during a conference call led by Chief Executive Officer Dipal Doshi, President of Research and Development Natarajan Sethuraman, and Laurent Servais, professor of paediatric neuromuscular diseases at the University of Oxford and an investigator in the study.
Entrada said the trial met its primary objective at the 6 mg/kg dose of ENTR-601-44. Cohort 1 enrolled eight ambulatory participants ages 6 to 17, randomized 3-to-1 to receive ENTR-601-44 or placebo via intravenous infusion on days 1, 43 and 85. Muscle biopsies were performed at screening and six weeks after the last dose.
According to Sethuraman, all treatment-emergent adverse events were mild to moderate, with headache the most common adverse event. No serious adverse events were reported, and no adverse events led to discontinuation. He also said no renal safety concerns were observed, with kidney function markers including eGFR, cystatin C and magnesium within normal ranges and comparable to placebo.
All eight participants have moved into the open-label portion of the study, receiving six additional doses of ENTR-601-44 at 6 mg/kg.
Entrada reported “earlier than expected functional responses,” including a statistically significant improvement in treated participants’ time-to-rise velocity versus placebo. Time-to-rise velocity is intended to measure motor function in DMD and, according to Sethuraman, is an approvable clinical endpoint in phase III studies.
The company reported a mean change in time-to-rise velocity of 0.08 rises per second, which Sethuraman said is 3.5 times higher than the minimal clinically important difference threshold of 0.023. Positive changes were reported across a majority of participants regardless of age or disease severity. Entrada also reported a positive trend in the 10-meter walk/run assessment.
At the same time, Entrada said plasma exposure in pediatric DMD patients was about 50% lower than levels seen in healthy adult volunteers and healthy non-human primates. Sethuraman said the lower exposure was consistent with data from juvenile non-human primate studies. The company reported exon skipping and dystrophin levels each about 2.3% above baseline, with one treated patient showing dystrophin of approximately 6% at day 127.
Sethuraman said Entrada updated its pharmacokinetic modeling and expects higher plasma concentration, exon skipping and dystrophin production in later cohorts. Doshi said the company expects “double-digit dystrophin levels” in Cohort 2, which is evaluating 12 mg/kg, and a further increase in Cohort 3.
Entrada executives pointed to the company’s delivery platform as a potential explanation for the functional signal. Sethuraman said the company believes ENTR-601-44 can access quiescent satellite cells, which are involved in muscle repair and regeneration.
Servais provided additional clinical context on DMD, describing dystrophin as the “shock absorber” of muscle cells. He said DMD affects multiple muscle groups, including the heart, and creates significant burdens for patients, families and society. Servais also noted that muscle biopsy results provide only a “snapshot” at a specific point in time and location, and that dystrophin expression may be time-sensitive.
Doshi said additional patients are being dosed in Cohort 2 of ELEVATE-44-201 at 12 mg/kg. Entrada expects to report data from both the Cohort 1 open-label period and Cohort 2 by the end of 2026.
The company also said its ELEVATE-45-201 study is fully enrolled, with Cohort 1 data expected in mid-2026. Doshi said Entrada expects plasma exposures in ELEVATE-45-201 to be similar to those seen in ELEVATE-44-201 Cohort 1, which could imply lower-than-expected exon skipping and dystrophin, but potential functional improvement at the 5 mg/kg dose.
Beyond ENTR-601-44 and ENTR-601-45, Entrada said ENTR-601-50 has received regulatory authorization from the U.K.’s MHRA and Research Ethics Committee. Doshi said the company plans to apply learnings from the 44 and 45 programs to the 50 and 51 programs before providing more detail later this year.
Entrada also highlighted progress outside DMD. Doshi said partner Vertex continues to enroll and dose the multiple ascending dose portion of the GALILEO phase I/II study of VX-670 in people with myotonic dystrophy type 1, with results expected in the second half of 2026. Entrada also plans to nominate a second inherited retinal disease candidate in the second half of 2026, following ENTR-801, its Usher syndrome type 2A candidate.
Doshi said Entrada has cash runway into the third quarter of 2027 and is positioned for multiple clinical catalysts across DMD and DM1.
Entrada Therapeutics (NASDAQ: TRDA) is a clinical-stage biotechnology company focused on enabling the development of protein-based therapeutics that can cross cell membranes and engage intracellular targets. Using its proprietary cell-penetrating miniature protein (CPMP) platform and intracellular targeting of proteins (iTOP) delivery technology, Entrada aims to expand the range of diseases addressable by large-molecule drugs.
The company’s pipeline includes programs in rare and serious diseases where conventional biologics have limited intracellular activity.
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