Dyne Therapeutics (DYN) Study Update summary

Study Overview and Objectives

• DELIVER is a global Phase 1/2 trial evaluating DYNE-251 in DMD patients amenable to exon 51 skipping, enrolling ambulant and non-ambulant males aged 4–16 years.

• The trial includes a 24-week randomized placebo-controlled period, a 24-week open-label extension, and a 96-week long-term extension.

• Primary endpoints are safety, tolerability, and change in dystrophin levels by Western blot; secondary endpoints include functional tests such as NSAA, SV95C, and pharmacokinetics.

• The FORCE platform aims for broad muscle tissue distribution, including cardiac and diaphragm muscles.

• Baseline characteristics show a diverse patient population in age, BMI, corticosteroid use, and prior DMD therapy.

Key Results and Efficacy Findings

• DYNE-251 at 20 mg/kg achieved 3.71% unadjusted and 8.72% muscle content-adjusted dystrophin at six months, the highest reported for exon 51 skipping therapies.

• Functional improvements were observed in multiple endpoints (NSAA, SV95C, 10-MWR, Time to Rise), with sustained gains from 6 to 12 months in the 10 mg/kg cohort.

• Both 10 mg/kg and 20 mg/kg cohorts met the EMA's minimal clinically important difference for SV95C.

• Dystrophin and functional improvements were dose-dependent and correlated with higher drug exposure.

• Functional benefit was consistent across cohorts with varying baseline characteristics, indicating broad applicability.

Safety and Tolerability

• DYNE-251 demonstrated a favorable safety profile across 54 participants and over 675 doses, representing more than 50 patient-years.

• Most adverse events were mild or moderate; two to three serious adverse events occurred in the 40 mg/kg cohort, with full recovery and no persistent anemia, thrombocytopenia, or kidney injury.

• The most common TEAEs included pyrexia, nasopharyngitis, headache, vomiting, fall, and infusion-related reactions.

• All participants are now dosed at 20 mg/kg, and ongoing monitoring continues.

• Regulators have been supportive of the safety management plan and dose adjustments.