Dyne Therapeutics Achieves Milestone in Duchenne Muscular Dystrophy Treatment

Dyne Therapeutics, Inc., a clinical-stage company focused on muscle disease therapies, has announced new clinical data from its ongoing Phase 1/2 DELIVER trial of DYNE-251 for Duchenne muscular dystrophy (DMD) patients with mutations amenable to exon 51 skipping. The data revealed significant improvements in dystrophin expression and functional performance across multiple cohorts.

Dr. Wildon Farwell, Chief Medical Officer at Dyne, highlighted the transformative potential of these findings, noting that DYNE-251 has achieved the highest dystrophin expression levels reported for an exon 51 skipping therapy. A significant functional improvement in multiple endpoints was also observed over time. The treatment showed substantial benefits in SV95C, an approved primary endpoint for Duchenne clinical trials in Europe, prompting Dyne to initiate registrational cohorts in DELIVER. An update on the registration pathway is expected by the end of 2024.

The DELIVER trial's assessment included 6-month biomarker and functional data from eight male patients in the 20 mg/kg cohort and 12-month functional data from six participants in the 10 mg/kg cohort. DYNE-251 demonstrated dose-dependent exon skipping and dystrophin expression, with notable improvements in functional endpoints in both cohorts.

Key findings include:
- Dystrophin Expression: The 20 mg/kg cohort of DYNE-251 showed a mean absolute dystrophin expression of 3.71% of normal, over ten times higher than the 0.3% reported for eteplirsen, a standard care treatment. Adjusted for muscle content, this figure rose to 8.72%, surpassing levels reported by peptide conjugate PMOs in development.
- Functional Improvements: Both the 20 mg/kg and 10 mg/kg cohorts demonstrated meaningful improvements in functional measures such as the North Star Ambulatory Assessment (NSAA), Stride Velocity 95th Centile (SV95C), 10-Meter Walk/Run Time (10-MWR), and Time to Rise from Floor. The 10 mg/kg cohort continued to improve from 6 to 12 months. Changes in SV95C from baseline in both cohorts met the European Medicines Agency's minimal clinically important difference (MCID).

Safety and tolerability data, derived from 54 participants, indicate DYNE-251’s favorable safety profile, with most adverse events being mild or moderate. No serious treatment-related adverse events have been identified, except for two participants at the 40 mg/kg dose level, both of whom have recovered. The DELIVER trial has administered approximately 675 doses, equivalent to over 50 patient-years of follow-up.

Looking forward, Dyne is initiating registrational cohorts in the DELIVER trial based on these findings and regulatory discussions. They aim to provide an update on their registration pathway by the year's end. Additionally, Dyne is conducting the Phase 1/2 ACHIEVE trial for DYNE-101 in myotonic dystrophy type 1, which has shown a favorable safety profile up to the 6.8 mg/kg cohort. Updates on DYNE-101’s registration pathway and further clinical data are also planned for the end of 2024.

Dyne Therapeutics has scheduled a video webcast today to discuss these DELIVER trial data. The event, which includes a presentation and a replay available for 90 days, will be accessible through their website.

The DELIVER trial is a global Phase 1/2 clinical trial evaluating DYNE-251. It consists of a 24-week multiple ascending dose randomized placebo-controlled period, a 24-week open-label extension, and a 96-week long-term extension. The trial's primary endpoints are safety, tolerability, and changes in dystrophin levels. Secondary endpoints include muscle function measures, exon skipping, and pharmacokinetics.

DYNE-251, under evaluation for DMD patients amenable to exon 51 skipping, aims to deliver targeted muscle tissue therapy via a phosphorodiamidate morpholino oligomer (PMO) conjugated to a fragment antibody (Fab). The goal is to generate a truncated, functional dystrophin protein to halt or reverse disease progression. The U.S. FDA has granted DYNE-251 fast track, orphan drug, and rare pediatric disease designations for this treatment.

Dyne Therapeutics is developing therapies for genetically driven muscle diseases, leveraging its FORCE™ platform to enhance tissue delivery of therapeutics. Their pipeline includes programs for myotonic dystrophy type 1 (DM1), Duchenne muscular dystrophy (DMD), and facioscapulohumeral muscular dystrophy (FSHD).

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