Dyne Therapeutics presents data highlighting FORCE platform

Dyne Therapeutics announced that previously reported clinical and preclinical data across its pipeline will be featured in poster presentations at the 29th Annual Congress of the World Muscle Society, held virtually and in Prague, Czech Republic, October 8-12, 2024. The presentations highlight the promise of the FORCE platform to deliver targeted therapeutics to address neuromuscular diseases. The Phase 1/2 DELIVER trial evaluating DYNE-251 in males with Duchenne muscular dystrophy mutations amenable to exon 51 skipping includes 6-month biomarker and functional data from patients enrolled in the 20 mg/kg cohort and 12-month functional data from the 10 mg/kg cohort. DYNE-251 demonstrated dose dependent exon skipping and dystrophin expression and improvement in multiple functional endpoints in both cohorts. Patients treated with 20 mg/kg of DYNE-251 Q4W had a mean absolute dystrophin expression of 3.7% of normal and when adjusting for muscle content, it reached 8.7%. Importantly, treatment with DYNE-251 resulted in meaningful improvements in Stride Velocity 95th Centile, a digital objective outcome measure of ambulatory performance in a patient’s normal daily environment. The change from baseline in SV95C met the published minimal clinically important difference as defined by the European Medicines Agency at 6 months for both the 10 and 20 mg/kg cohorts. The Phase 1/2 ACHIEVE trial evaluating DYNE-101 in adult participants with myotonic dystrophy type 1 includes 12-month data from the 1.8 mg/kg Q4W cohort, 6-month data from the 3.4 mg/kg Q4W cohort, and 3-month data from the 5.4 mg/kg Q8W cohort. DYNE-101 demonstrated robust muscle delivery and dose-dependent, consistent splicing correction while also showing improvement in myotonia, muscle strength, and timed function tests and in the Myotonic Dystrophy Type 1 Activity and Participation Scale and the Myotonic Dystrophy Health Index patient reported outcomes. Patients in the 5.4 mg/kg Q8W cohort had a 27% mean splicing correction from baseline across a broad, 22-gene panel at 3 months, with all participants demonstrating splicing correction. Both DYNE-251 and DYNE-101 have demonstrated favorable safety profiles. Preclinical data for DYNE-302 in facioscapulohumeral muscular dystrophy, demonstrated robust and durable DUX4 suppression and functional benefit in an innovative hTfR1/iFLExD mouse model developed by Dyne. In hTfR1/iFLExD mice, a single intravenous dose of DYNE-302 resulted in dose-dependent and robust reduction of the DUX4 transcriptome that lasted up to three months, with benefit on muscle structure and function. Preclinical data in a Pompe disease model demonstrated the potential of the FORCE platform to deliver enzyme replacement therapy to cardiac and skeletal muscle and the central nervous system, potentially expanding the modularity of the platform beyond oligonucleotides.