Entrada Therapeutics (TRDA) Study result summary

Study overview and design

• ELEVATE-44-201 is a global, randomized, double-blind, placebo-controlled Phase 1/2 study in ambulatory DMD patients aged 4–20 amenable to exon 44 skipping, with 24 participants across three cohorts.

• Cohort 1 included eight participants (6 treated, 2 placebo), all ambulatory and on stable corticosteroids, with a mean age of 9.3 years and low baseline dystrophin levels.

• Participants received three intravenous doses of 6 mg/kg ENTR-601-44 or placebo, with muscle biopsies at baseline and day 127.

• The study includes a double-blind period, open-label extension, and follow-up, with all Cohort 1 participants transitioning to the open-label phase.

• Primary objective is safety and tolerability; secondary objectives include pharmacokinetics, exon skipping, dystrophin production, and functional measures.

Safety and tolerability

• All adverse events in Cohort 1 were mild to moderate, with no serious adverse events, discontinuations, or deaths.

• Headache was the most common adverse event, occurring equally in treatment and placebo groups.

• No hypomagnesemia or renal safety concerns; kidney function markers (eGFR, Cystatin C, magnesium) remained within normal ranges and comparable to placebo.

• All events resolved, and no deaths occurred during the study.

Pharmacokinetics and biomarker findings

• Plasma exposure (Cmax, AUC) in pediatric participants was lower than predicted and lower than in healthy adults, leading to lower exon skipping and dystrophin expression in Cohort 1.

• Mean increase in exon skipping was 2.31% and in MHC-normalized dystrophin was 2.36% at 6 mg/kg, with one patient reaching approximately 6%.

• Updated PK modeling, incorporating juvenile NHP data, predicts higher plasma AUC, exon skipping, and dystrophin levels in Cohorts 2 and 3 at increased doses.

• Initial PK projections overestimated exposures due to reliance on adult data; new analysis supports higher efficacy in future cohorts.