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 translation from preclinical disease models to well-defined and rapid clinical development paths to approval.
Our therapies under development consist of three components: a proprietary antibody, a clinically validated linker and an oligonucleotide payload that we attach to our antibody using the linker.
Myotonic Dystrophy Type 1 (DM1)
DM1 is a rare, progressive genetic disease that is estimated to affect over 40,000 people in the United States and over 74,000 people in the European Union. DM1 is a monogenic, autosomal dominant, progressive disease caused by an abnormal expansion in a region of the DMPK gene.
Our DM1 program candidates consist of a proprietary antibody conjugated with our linker to an antisense oligonucleotide (ASO). They are 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 reversing disease. In preclinical studies, we have observed correction of splicing changes in DM1 patient cells, reversal of myotonia after a single dose in a DM1 model and enhanced muscle distribution as evidenced by reduced levels of cytoplasmic wild type DMPK RNA.
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. DMD is estimated to affect approximately 12,000 to 15,000 people in the U.S. and approximately 25,000 people in the E.U. Mutations in the dystrophin gene lead to certain exons being misread, thus resulting in the loss of function of the dystrophin protein, muscle cell death and progressive loss of muscle function.
Our DMD program candidates consist of a proprietary antibody conjugated with our linker to a phosphorodiamidate morpholino oligomer (PMO). They are designed to deliver a PMO to muscle tissue to promote the skipping of specific DMD exons in the nucleus, allowing muscle cells to create a more complete, functional dystrophin protein and stop or reverse disease progression. In in vitro and in vivo preclinical studies, our candidates have shown increased exon skipping, increased dystrophin expression, reduced muscle damage and increased muscle function. Our initial development efforts in DMD are focused on developing a therapy for patients with mutations amenable to skipping Exon 51. We plan to expand our DMD franchise and develop therapies for patients with other exon mutations, including mutations in Exons 53, 45 and 44.
Facioscapulohumeral Muscular Dystrophy (FSHD)
FSHD is a rare disease characterized by progressive skeletal muscle loss and affects an estimated 16,000 to 38,000 people in the U.S. and approximately 35,000 people in the E.U. 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 program candidates consist of a proprietary antibody conjugated with our linker to an ASO 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 gives Dyne 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 intend to utilize our FORCE platform to expand our portfolio by pursuing the development of programs in additional indications, including 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.