Entrada Therapeutics Shares Promising Phase 1 Data for Duchenne Muscular Dystrophy Trial

Entrada Therapeutics, Inc., a clinical-stage biopharmaceutical company, recently announced promising preliminary results from its Phase 1 clinical trial, ENTR-601-44-101. The data will be presented at the 29th Annual Congress of the World Muscle Society in Prague from October 8-12, 2024.

Dipal Doshi, CEO of Entrada Therapeutics, highlighted the positive outcomes of the trial. ENTR-601-44 was well-tolerated among healthy volunteers, showing significant plasma and muscle concentrations and exon skipping, which are crucial indicators for the upcoming Phase 2 patient trials. The trial's results suggest that a clinically meaningful starting dose has been identified for the next phase.

The primary goal of the Phase 1 trial was to assess the safety and tolerability of a single dose of ENTR-601-44. It also aimed to evaluate pharmacokinetics and target engagement, specifically exon skipping in skeletal muscle. The study involved 32 healthy male volunteers divided into four cohorts, with each cohort receiving different doses: 0.75 mg/kg, 1.5 mg/kg, 3 mg/kg, and 6 mg/kg. In each cohort, six participants received ENTR-601-44 and two received a placebo.

The trial observed no serious or drug-related adverse events and no significant changes in vital signs, ECGs, physical exams, or laboratory assessments. Notably, muscle concentration was detected in all subjects in the 6 mg/kg dose cohort, with a mean concentration of 53.8 ng/g. The mean target engagement measured by exon skipping was 0.44%, which was statistically significant compared to the placebo.

Francesco Muntoni, MD, a Professor of Paediatric Neurology, expressed optimism regarding these preliminary results. He noted that the data could represent a transformative treatment option for boys and young men with Duchenne muscular dystrophy (DMD) who are exon 44 skipping amenable. The safety data and the potential for dosing intervals of at least six weeks could significantly reduce the treatment burden for patients.

Based on the positive Phase 1 data, Entrada Therapeutics plans to submit regulatory applications in Q4 2024 to initiate global Phase 2 clinical trials for ENTR-601-44 and ENTR-601-45. Additionally, the company aims to submit applications in 2025 for a Phase 2 trial of its third Duchenne candidate, ENTR-601-50, for patients who are exon 50 skipping amenable.

ENTR-601-44, the lead candidate within Entrada's Duchenne muscular dystrophy portfolio, utilizes a proprietary Endosomal Escape Vehicle (EEV™)-conjugated phosphorodiamidate morpholino oligomer (PMO). This investigational therapy targets the underlying genetic cause of DMD by addressing mutations or missing exons in the DMD gene, potentially allowing for the production of a functional dystrophin protein.

Duchenne muscular dystrophy is a severe genetic disorder characterized by progressive muscle degeneration and weakness. It results from mutations in the DMD gene, leading to insufficient dystrophin production crucial for muscle cell integrity. DMD progressively impairs muscle function, affecting mobility and causing severe heart and respiratory complications.

Entrada Therapeutics is dedicated to developing innovative treatments that engage previously inaccessible intracellular targets. Their EEV-therapeutics are designed for efficient delivery into various tissues, aiming to improve the therapeutic index. The company's pipeline includes RNA-, antibody-, and enzyme-based programs targeting neuromuscular, ocular, metabolic, and immunological diseases. Their lead oligonucleotide programs focus on treating different subpopulations of Duchenne patients.

ENTR-601-44's promising Phase 1 results mark a significant step towards potentially effective treatments for DMD, providing hope for improved quality of life for patients suffering from this debilitating disease.