We are building a leading muscle disease company focused on advancing innovative, life-transforming therapies for genetically driven diseases. Our initial focus is on myotonic dystrophy type 1 (DM1), Duchenne muscular dystrophy (DMD) and facioscapulohumeral muscular dystrophy (FSHD). Each of these disorders has a profound impact on affected communities around the world.
We are utilizing our proprietary FORCETM platform to overcome the current limitations of muscle tissue delivery and advance modern oligonucleotide therapeutics for muscle diseases. In selecting diseases to target with our FORCE platform, we seek those with clear translational potential from preclinical disease models to well-defined clinical development and regulatory pathways.
|Myotonic Dystrophy Type 1 (DM1) Myotonic Dystrophy Type 1 (DM1) Information||DMPK||
Safety, Tolerability & Splicing Data Expected in H2’23
|Duchenne Muscular Dystrophy (DMD) Duchenne Muscular Dystrophy (DMD) Information||
Safety, Tolerability & Dystrophin Data Expected in H2’23
|Facioscapulohumeral Muscular Dystrophy (FSHD) Facioscapulohumeral Muscular Dystrophy (FSHD) Information||DUX4||
|Pipeline Expansion Opportunities|
Metabolic Rare Skeletal
Cardiac Metabolic Information
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 product candidate, DYNE-101, consists of a proprietary Fab conjugated with our linker 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.
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 product candidate 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 impressive exon skipping in non-human primates, especially in the heart and diaphragm, muscles that weaken over time in people living with DMD leading to mortality.
We plan to expand our DMD franchise and develop therapies for patients with mutations amenable to skipping other exons, including exons 53, 45 and 44.
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.
We intend to utilize our FORCE platform to expand our portfolio by pursuing the development of programs in additional indications, including additional rare skeletal, cardiac and metabolic muscle diseases. By rationally selecting therapeutic payloads to conjugate with our proprietary antibody and linker, we believe we can develop product candidates to address the genetic basis of additional muscle diseases.Back to the pipeline