Dyne Therapeutics (DYN) Study Update summary

Study design and patient population

• DELIVER is a global Phase 1/2 trial for 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 muscle function, exon skipping, and pharmacokinetics.

• Participants previously treated with exon skipping therapy can enroll after a 12-week washout.

• The study enrolled a diverse population in age, BMI, corticosteroid use, and prior DMD therapy, representative of the broader DMD community.

Efficacy and functional outcomes

• DYNE-251 demonstrated dose-dependent increases in PMO muscle concentration, exon skipping, and dystrophin production, with 3.71% unadjusted and 8.72% muscle content-adjusted dystrophin at 20 mg/kg, over tenfold higher than standard of care.

• Functional improvements were observed in NSAA, SV95C, 10-meter walk/run, and Time to Rise, with benefits increasing over time and after dose escalation.

• Both 10 mg/kg and 20 mg/kg cohorts met the EMA's minimal clinically important difference for SV95C, supporting real-world benefit.

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

• Data from the 10 mg/kg cohort showed sustained benefit up to one year.

Safety profile and regulatory engagement

• DYNE-251 has shown a favorable safety profile across over 50 patient-years and 675 doses, with most adverse events mild or moderate.

• Two serious adverse events occurred in the 40 mg/kg cohort, both with confounding factors and full recovery; all participants are now dosed at 20 mg/kg.

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

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

• DYNE-251 has fast track, orphan drug, and rare pediatric disease designations from the FDA.