Initial Data from the DELIVER Trial of DYNE-251 in Males with DMD Mutations Amenable to Exon 51 Skipping

Topic:

Clinical Trials

Poster Number: M156

Author(s):

Kevin Flanigan, Nationwide Children's Hospital, Columbus, OH, USA, Craig Campbell, University of Western Ontario, Department of Paediatrics, Children’s Hospital London Health Sciences, London, Ontario, Canada, Nicolas Deconinck, MD, Neuromuscular Reference Center UZ Gent, Gent, Belgium, Liesbeth De Waele, MD, University Hospitals Leuven, Leuven, Belgium, Michelle Lorentzos, MD, Children's Hospital at Westmead, Westmead, New South Wales, Australia, Han Phan, MD, Rare Disease Research, LLC., Atlanta, GA, USA, Perry Shieh, MD, PhD, University of California Los Angeles, Los Angeles, CA, USA, Chris Mix, MD, Dyne Therapeutics, Inc. Waltham, MA, USA, Soma Ray, Dyne Therapeutics, Inc. Waltham, MA, USA, Dazhe Wang, Dyne Therapeutics, Inc. Waltham, MA, USA, Wildon Farwell, MD, Dyne Therapeutics, Inc. Waltham, MA, USA, Ash Dugar, PhD, MBA, Dyne Therapeutics, Inc., Waltham, MA, USA, Maria Naylor, PhD, Dyne Therapeutics, Inc., Waltham, MA, USA, Michela Guglieri, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle-Upon-Tyne, UK

Duchenne muscular dystrophy (DMD) is a rare neuromuscular disorder caused by absence of functional dystrophin protein. Most therapeutic strategies are focused on restoring dystrophin expression as low residual levels can delay disease progression. One approach uses phosphorodiamidate morpholino oligomer (PMO)-induced exon skipping to restore the DMD mRNA reading frame leading to the production of truncated, functional dystrophin protein. However, the therapeutic potential of approved PMO therapies is limited by poor delivery to muscle.

The FORCE™ platform, developed to overcome this limitation, harnesses the natural expression of transferrin receptor (TfR)1 on muscle for targeted delivery of oligonucleotides. DYNE-251 is an investigational therapeutic for DMD designed based on the principles of the FORCE platform. It consists of an exon 51-skipping PMO conjugated to a TfR1-targeting fragment antibody with the goal of delivering increased levels of PMO to affected muscles.

The safety and efficacy of every-4-weeks intravenous administrations of DYNE-251 are being studied in the Phase 1/2 DELIVER trial in ambulant and non-ambulant males aged 4 to 16 with DMD mutations amenable to exon 51 skipping (NCT05524883). Primary endpoints include safety, tolerability, and change from baseline in dystrophin levels in muscle measured by Western blot. Secondary endpoints include measures of muscle function, exon skipping, and pharmacokinetics.

As of October 30, 2023, 32 participants were enrolled across five dose level cohorts [0.7 mg/kg (n=6), 1.4 mg/kg (n=6), 2.8 mg/kg (n=6), 5 mg/kg (n=6), and 10 mg/kg PMO (n=8)] with >175 doses of study drug administered. Enrollment was complete through the 10 mg/kg cohort and all participants who completed the 24-week placebo-controlled portion of the study had entered the 24-week open-label extension. No participants demonstrated treatment-emergent anemia and there were no discontinuations. Safety and tolerability data from multiple cohorts and dystrophin expression data from the 5 mg/kg cohort at 25 Weeks will be presented.