Dyne Therapeutics’ novel exon-skipping molecules have favorable safety profiles, lead to pronounced exon skipping in the heart, diaphragm, and quadriceps in a nonhuman primate model of Duchenne muscular dystrophy (DMD), and achieve higher levels of exon skipping in myotubes derived from patients with DMD.

These results were presented at the 27th International Hybrid Annual Congress of the World Muscle Society that took place in Halifax, Nova Scotia, Canada, from October 11 to 15, 2022.

The novel molecules are part of Dyne Therapeutics’ FORCE platform, which targets transferrin receptor 1. This receptor is highly expressed on the surface of muscle cells. In the exon-skipping molecules, a phosphorodiamidate morpholino oligomer that is designed to skip specific exons in the DMD gene is conjugated to FORCE so that it is carried to muscle cells. This way, a truncated, but still functional, dystrophin protein can be made in muscle cells, which could stop or even reverse the progression of DMD.


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The chief scientific officer of Dyne Therapeutics, Oxana Beskrovnaya, PhD, said in a press release, “We are excited to present data which highlight the potential of our FORCE™ platform in building a global DMD franchise of exon skipping therapies.”

Data from 2 exon-skipping molecules were presented during the congress. The first was DYNE-251, which is designed to skip exon 51, and the second was another FORCE conjugate targeting exon 53, for which the first in vitro data were presented. According to Dyne’s findings, exon 53 skipping achieved with the FORCE conjugate was dose responsive and induced the restoration of dystrophin protein.

DYNE-251 is currently being tested in a phase 1/2 clinical trial in patients with DMD, and data are expected to be reported in the second half of 2023.

Reference

Dyne Therapeutics presents preclinical data from its Duchenne muscular dystrophy programs targeting exons 51 and 53 at World Muscle Society 2022 Congress. News release. Dyne Therapeutics, Inc; October 11, 2022.