First Patient Has Received DYNE-251 in DELIVER Trial, Dyne Announces

The company plans to report data from the first part of the study in 2Q 2023

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by Andrea Lobo |

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The first patient has received Dyne Therapeutics‘ investigational therapy DYNE-251 for treating Duchenne muscular dystrophy (DMD), the company has announced. The therapy is being tested in the DELIVER Phase 1/2 clinical trial and is indicated for patients with mutations amenable to exon 51 skipping.

“We are excited to bring our FORCE platform to the clinic for the first time with the initiation of patient dosing in the DELIVER trial,” Wildon Farwell, MD, chief medical officer of Dyne said in a company press release. Dyne is “focused on driving toward meaningful clinical data, including dystrophin, to understand the potential of DYNE-251 in DMD.”

DMD-causing mutations can result in missing exons  — segments within the gene important for protein production — leading to low levels or no dystrophin protein production and ultimately resulting in progressive muscle damage since dystrophin protects the integrity and structure of muscle fibers.

DYNE-251 is an exon-skipping therapy, composed of phosphorodiamidate morpholino oligomers (PMOs; short synthetic molecules) that allow exon 51 to be “skipped.” As a result, a smaller, but functional dystrophin protein is produced.

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The effectiveness of currently approved therapeutics using PMOs is limited by poor muscle delivery. Dyne developed a technology called FORCE platform wherein PMOs are linked to an antibody that binds a specific receptor (in this case, transferrin receptor 1 or TfR1) on muscle cells. This approach has several advantages including targeted delivery to muscle tissue, extended time between doses, and targeting the genetic basis of the disease to stop or reverse its progression, according to the company.

In a DMD mouse model, Dyne FORCE platform delivered its exon-skipping therapy directly to muscles, resulting in increased dystrophin production in skeletal and cardiac muscles, with reduced muscle damage and increased muscular function. Also, DYNE-251 was found to be safe and achieved exon-skipping in nonhuman primates, especially in the heart and diaphragm, according to the company’s website.

The DELIVER trial (NCT05524883) is a Phase 1/2 global clinical trial to evaluate DYNE-251’s  safety and tolerability, and to determine dystrophin protein levels in muscle tissue in DMD patients with mutations responsive to exon 51 skipping therapy.

The trial is expected to enroll about 46 males with DMD who can and cannot walk, aged 4–16. It consists of 3 periods: a multiple ascending dose randomized placebo-controlled period (24 weeks), an open-label extension (24 weeks), and a long-term extension (96 weeks).

Dyne intends to report data from the first part of the study in the second half of 2023. After the first period concludes, all patients will transition to DYNE-251 treatment in the open-label and long-term extensions.

“There is a significant need for new therapies for people living with Duchenne. The comprehensive preclinical data supporting DYNE-251 demonstrate the magnitude of dystrophin expression in cardiac and skeletal muscle. We look forward to being a part of the DELIVER trial to understand the potential of DYNE-251”  Kevin Flanigan, MD, said. Flanigan is the Robert F. and Edgar T. Wolfe Foundation Endowed Chair in Neuromuscular Research and the director of the Center for Gene Therapy in The Research Institute at Nationwide Children’s Hospital, Columbus, Ohio.

Dyne hosted a virtual event called “Spotlight on the Clinic” on Sept. 12 that focused on the clinical programs for DYNE-251 in DMD and similar therapies for other dystrophies, namely DYNE-101 for myotonic dystrophy type 1 (DM1).

“With our DYNE-251 and DYNE-101 clinical trials now underway, this is a very exciting time for Dyne and people living with DMD and DM1,” Joshua Brumm, president and CEO of Dyne, said in another company press release. “DELIVER and ACHIEVE [a Phase 1/2 trial testing DYNE-101] … are expected to report data in the second half of 2023, including evaluating important biomarkers of dystrophin in DMD.”