Myotonic Dystrophy Type 1 (DM1)

DM1 is a rare, progressive genetic disease that is estimated to affect more than 40,000 people in the United States and over 74,000 people in Europe. DM1 is a monogenic, autosomal dominant disease caused by an abnormal expansion in a region of the DMPK gene.

Our DM1 investigational therapeutic, DYNE-101, consists of a proprietary Fab conjugated to an antisense oligonucleotide (ASO). Our DM1 program is designed to address the genetic basis of DM1 by reducing the levels of mutant DMPK RNA in the nucleus, releasing splicing proteins, allowing normal mRNA processing and translation of normal proteins and potentially stopping or reversing disease. In preclinical studies, we have observed reduction of nuclear foci and correction of splicing in DM1 patient cells, robust reduction in toxic human nuclear DMPK and correction of splicing in a novel in vivo model developed by Dyne, reversal of myotonia in a DM1 disease model, and enhanced muscle distribution as evidenced by reduced levels of cytoplasmic wild type DMPK RNA in non-human primates. DYNE-101 was granted orphan drug designation by the European Medicines Agency for the treatment of DM1.

Duchenne Muscular Dystrophy (DMD)

DMD is a rare disease caused by mutations in the gene that encodes for dystrophin, a protein critical for the normal function of muscle cells. These mutations, the majority of which are deletions, result in the lack of dystrophin protein and progressive loss of muscle function. DMD occurs primarily in males and affects an estimated 12,000 to 15,000 individuals in the U.S. and 25,000 in Europe.

DYNE-251 is our investigational therapeutic being developed for people living with DMD who are amenable to exon 51 skipping. DYNE-251 consists of a phosphorodiamidate morpholino oligomer (PMO) conjugated to a proprietary Fab. It is designed to enable targeted muscle tissue delivery and promote exon skipping in the nucleus, allowing muscle cells to create a truncated, functional dystrophin protein, with the goal of stopping or reversing disease progression. In preclinical studies with the FORCE platform, robust and durable exon skipping and dystrophin expression were observed in the mdx mouse model in skeletal and cardiac muscles as well as reduced muscle damage and increased muscle function. DYNE-251 demonstrated a favorable safety profile and achieved robust exon skipping in non-human primates, especially in the heart and diaphragm, muscles in people living with DMD that weaken over time leading to mortality. DYNE-251 was granted fast track, orphan drug and rare pediatric disease-designations by the U.S. Food and Drug Administration for the treatment of DMD mutations amenable to exon 51 skipping.

In addition to DYNE-251, Dyne is building a global DMD franchise and has preclinical programs targeting other exons, including 53, 45 and 44.

Facioscapulohumeral Muscular Dystrophy (FSHD)

FSHD is a rare disease characterized by progressive, skeletal muscle loss that is estimated to affect approximately 16,000 to 38,000 people in the U.S. and 35,000 people in Europe. FSHD is caused by an aberrant expression of the DUX4 gene in muscle tissue, which leads to death of muscle and replacement by fat. Our FSHD candidate, DYNE-301, consists of our proprietary Fab conjugated with our linker to an ASO that is designed to address the genetic basis of FSHD by reducing DUX4 expression in muscle tissue. We have an agreement with the University of Mons that provides us with exclusive access to intellectual property to target the genetic cause of FSHD and complements our own proprietary platform for precision delivery into muscle cells. We generated proof-of-concept data showing that DYNE-301 reduced expression of key DUX4 biomarkers in FSHD patient myotubes.