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Abstract Details

Initial Data from the DELIVER Trial of DYNE-251 in Males with DMD Mutations Amenable to Exon 51 Skipping
Neuromuscular and Clinical Neurophysiology (EMG)
ES1 - Emerging Science 1 (11:33 AM-11:39 AM)
004

Duchenne muscular dystrophy (DMD) is caused by absence of functional dystrophin protein. Approved PMO therapies induce exon skipping to restore the DMD mRNA reading frame leading to the production of truncated, functional dystrophin, but their potential is limited by poor muscle delivery. DYNE-251, an investigational therapeutic for DMD, consists of an exon 51-skipping PMO conjugated to a TfR1-targeting Fab to deliver increased levels of PMO to muscles.

Determine the safety and efficacy of DYNE-251 in ambulant and non-ambulant males aged 4-16 with DMD mutations amenable to exon 51 skipping (Phase 1/2 DELIVER trial, NCT05524883).

In the MAD portion of DELIVER, participants are randomized to receive DYNE-251 or placebo Q4W for 6 months across 7 PMO dose levels up to 40 mg/kg. For analysis of exon skipping and dystrophin data from the 5 mg/kg cohort, 4 participants received DYNE-251 and 2 received placebo. Safety and tolerability are based on 37 participants enrolled in DELIVER as of the data cutoff date.

At 6 months, 5 mg/kg DYNE-251 showed a mean 657 ng/g PMO concentration in muscle and mean absolute exon skipping level of 0.90% (0.80% difference from baseline). Mean absolute dystrophin level, measured by Western blot, increased from 0.60% at baseline to 0.88% of normal at 6 months, and the mean level of dystrophin positive fibers (PDPF) increased from 2.4% at baseline to 22.2% at 6 months. As of the data cut-off date, DYNE-251 demonstrated a favorable safety profile with mostly mild or moderate TEAEs. There was no treatment-emergent anemia or clinically meaningful changes in kidney parameters or electrolytes.

Based on these initial data, DYNE-251 had a favorable safety profile and reached levels of dystrophin expression, exon skipping, and PDPF at 6 months that exceeded levels reported at the same time point in prior clinical trials evaluating the standard of care PMO.

Authors/Disclosures
Perry Shieh (UCLA)
PRESENTER
Dr. Shieh has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sarepta. Dr. Shieh has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech. Dr. Shieh has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Shieh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion. Dr. Shieh has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Argenx. Dr. Shieh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for UCB. Dr. Shieh has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for CSL Behring. Dr. Shieh has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Grifols. Dr. Shieh has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Alexion. Dr. Shieh has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Biogen. Dr. Shieh has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Genentech. Dr. Shieh has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Argenx. Dr. Shieh has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Catalyst.
Craig Campbell Dr. Campbell has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Catabasis. Dr. Campbell has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Solid. The institution of Dr. Campbell has received research support from Biogen. The institution of Dr. Campbell has received research support from Genzyme. The institution of Dr. Campbell has received research support from Acceleron, AMO, Biogen, Sarepta, Wave, PTC, Pfizer, Roche.
Nicholas Deconinck Nicholas Deconinck has received personal compensation in the range of $500-$4,999 for serving as a Consultant for biogen. Nicholas Deconinck has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for roche. Nicholas Deconinck has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for avexis. Nicholas Deconinck has received publishing royalties from a publication relating to health care.
No disclosure on file
Kevin Flanigan (Nationwide CHildrens Hospital) Dr. Flanigan has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sarepta. Dr. Flanigan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Apic Bio. Dr. Flanigan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AavantiBio. Dr. Flanigan has stock in 4D Molecular Therapeutics. The institution of Dr. Flanigan has received research support from Abeona Therapeutics. The institution of Dr. Flanigan has received research support from Sarepta Therapeutics. The institution of Dr. Flanigan has received research support from Astellas Therapeutics. Dr. Flanigan has received intellectual property interests from a discovery or technology relating to health care.
No disclosure on file
Han Phan (Rare Disease Research, LLC) Dr. Phan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Wave Biosciences. Dr. Phan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Stealth.
No disclosure on file
No disclosure on file
No disclosure on file
Wildon Farwell Dr. Farwell has received personal compensation for serving as an employee of Biogen. Dr. Farwell has received stock or an ownership interest from Biogen.
No disclosure on file
Maria Naylor Dr. Naylor has received personal compensation for serving as an employee of Biogen. Dr. Naylor has received stock or an ownership interest from Biogen.
Michela Guglieri The institution of Michela Guglieri has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pfizer. The institution of Michela Guglieri has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Dyne. The institution of Michela Guglieri has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for NS Pharma. Michela Guglieri has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sarepta. The institution of Michela Guglieri has received research support from EC - H2020. The institution of Michela Guglieri has received research support from Duchenne UK. The institution of Michela Guglieri has received research support from Sarepta. The institution of Michela Guglieri has received research support from DMD Research Fund.