zeleciment rostudirsen (DYNE-251) / Dyne Therap - LARVOL DELTA

DELIVER: Safety, Tolerability, Pharmacodynamic, Efficacy, and Pharmacokinetic Study of DYNE-251 in Participants With Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping (clinicaltrials.gov) - P1/2 | N=86 | Active, not recruiting | Sponsor: Dyne Therapeutics | Trial completion date: Nov 2029 ➔ Sep 2031 | Trial primary completion date: Nov 2029 ➔ Sep 2031

Trial completion date • Trial primary completion date • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Dyne Therapeutics Announces U.S. FDA Acceptance of Biologics License Application (BLA) for Z-Rostudirsen in Exon 51 Duchenne Muscular Dystrophy (DMD) (GlobeNewswire) - "The FDA has granted the BLA Priority Review and assigned a Prescription Drug User Fee Act (PDUFA) target action date of January 21, 2027. Dyne continues to expect a potential U.S. launch of z-rostudirsen in Q1 2027, assuming approval is received on the anticipated timeline....Submission for Accelerated Approval based on dystrophin as a surrogate endpoint."

FDA filing • Launch US • PDUFA • Priority review • Duchenne Muscular Dystrophy

FORZETTO, a Phase 3 Study of Z-Rostudirsen in Ambulatory Males With Exon 51 Amenable DMD (ICNMD 2026) - P1/2 | "Zeleciment rostudirsen (z-rostudirsen, also known as DYNE-251) leverages TfR1 to deliver an exon 51 skipping PMO to muscle, with the goal of producing near full-length, functional dystrophin... The Phase 3 FORZETTO study will further evaluate the clinical benefit and safety of z-rostudirsen in participants with DMD amenable to exon 51 skipping, with endpoints that measure functional improvement."

P3 data • CNS Disorders • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy • TFRC

Zeleciment Rostudirsen Increased Dystrophin and Led to Functional Improvement in Clinical Measures in DELIVER Trial (ICNMD 2026) - P1/2 | "Zeleciment rostudirsen (z-rostudirsen, also known as DYNE-251) leverages the transferrin receptor, TfR1, to deliver an exon 51 skipping Phosphorodiamidate Morpholino Oligomer (PMO) to muscle with the goal of producing near-full length functional dystrophin. In the Multiple Ascending Dose (MAD) portion of the Phase 1/2 DELIVER trial (NCT05524883), 54 participants received z-rostudirsen or placebo every 4 or 8 weeks for 6 months... Data from the DELIVER trial, including robust dystrophin expression, trends in functional improvement, favorable safety profile, and convenient dosing support the potential of z-rostudirsen to address the unmet needs of individuals with DMD pathogenic variants amenable to exon 51 skipping."

Clinical • TFRC

Efficacy, Safety, and Tolerability of Zeleciment Rostudirsen (DYNE-251) Administered Intravenously Every 4 Weeks in Ambulatory Participants With Duchenne Muscular Dystrophy (FORZETTO) (clinicaltrials.gov) - P3 | N=90 | Recruiting | Sponsor: Dyne Therapeutics

New P3 trial • Becker Muscular Dystrophy • CNS Disorders • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy • Myotonic Dystrophy

Dyne Therapeutics Announces Submission of Biologics License Application (BLA) to U.S. FDA for Z-Rostudirsen in Exon 51 Duchenne Muscular Dystrophy (DMD) (The Manila Times) - "Dyne has requested Priority Review for the BLA, which, if granted, would shorten the review process from 10 months to 6 months following the FDA’s 60-day filing review period. Dyne continues to expect a potential U.S. launch of z-rostudirsen in Q1 2027, assuming the FDA grants Priority Review and approval is received on the anticipated timeline."

FDA filing • Launch US • Duchenne Muscular Dystrophy

Dyne Therapeutics…announced the initiation of the Phase 3 FORZETTO trial of zeleciment rostudirsen (z-rostudirsen, also known as DYNE-251), in individuals with Duchenne muscular dystrophy (DMD) amenable to exon 51 skipping (GlobeNewswire) - "The design of the FORZETTO trial will be presented at the 19th International Congress on Neuromuscular Diseases (ICNMD) being held July 7-11, 2026, in Florence, Italy....FORZETTO is a global, randomized, placebo-controlled, double-blind, confirmatory Phase 3 trial designed to assess the efficacy, safety, and tolerability of z-rostudirsen administered intravenously to ambulatory male participants with DMD amenable to exon 51 skipping. The trial will enroll approximately 90 participants 4 to 18 years of age who will be randomized 1:1 to receive 20 mg/kg of z-rostudirsen or placebo every four weeks (Q4W). The first trial site is activated and open to enrollment."

Clinical protocol • Trial status • Duchenne Muscular Dystrophy

EXPERT CONSENSUS ON TREATMENT GUIDANCE FOR FDA-APPROVED AND SECOND-GENERATION EXON-SKIPPING THERAPIES IN DUCHENE MUSCULAR DYSTROPHY (DMD): A RAND/UCLA MODIFIED DELPHI PANEL (ISPOR 2026) - "We aimed to characterize the current therapeutic landscape for DMD, including exon-skipping therapies, gene therapy, and givinostat, as well as emerging second-generation exon-skipping agents. Using the RAND/UCLA modified Delphi panel method, nine US experts (seven pediatric neurologists, two physical therapists) rated the likelihood of recommending FDA-approved therapies (eteplirsen, golodirsen, viltolarsen, casimersen, GT, givinostat) and the anticipated clinical value of investigational therapies with Phase 1/2 data (delpacibart zotadirsen, DYNE-251, WVE-N531, and NS-089/NCNP-02)... The panel reached consensus that approved exon-skipping therapies provide modest benefit, particularly in earlier stages, while early data suggest that second-generation exon-skippers may have the potential to offer greater functional improvement. However, trials remain in early stages, and the full risks and benefits of these therapies are not yet known. The findings highlight the rapidly..."

Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy

Dyne Therapeutics Announces Upcoming Presentations Across Neuromuscular Pipeline at 2026 MDA Clinical & Scientific Conference (GlobeNewswire) - "Dyne’s posters and presentations at the 2026 MDA Clinical & Scientific Conference will include: (i) New analyses of the results of the DELIVER clinical trial of zeleciment rostudirsen (z-rostudirsen, also known as DYNE-251) in exon 51 skip amenable DMD; (ii) The design of a Phase 3 clinical trial assessing zeleciment basivarsen (z-basivarsen, also known as DYNE-101) in DM1."

Clinical protocol • P1/2 data • Duchenne Muscular Dystrophy • Myotonic Dystrophy

Topline data from Registrational Expansion Cohort of DELIVER trial of zeleciment rostudirsen (z-rostudirsen, also known as DYNE-251) in DMD on track for December 2025 to support potential submission for U.S. Accelerated Approval in Q2 2026 (The Manila Times)

FDA approval • P1/2 data • Duchenne Muscular Dystrophy

Z-rostudirsen remains on track for potential launch in Q1 2027 (The Manila Times)

Launch US • Duchenne Muscular Dystrophy

Dyne Therapeutics Receives Orphan Drug Designation in Japan for DYNE-251 in Duchenne Muscular Dystrophy (GlobeNewswire) - "Data from ongoing DELIVER trial demonstrated sustained functional improvement through 18 months; results from Registrational Expansion Cohort expected late 2025."

Orphan drug • P1/2 data • Duchenne Muscular Dystrophy

Dyne Therapeutics Announces FDA Breakthrough Therapy Designation for DYNE-251 in Duchenne Muscular Dystrophy (DMD) (The Manila Times) - "Dyne Therapeutics, Inc...announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to DYNE-251 for the treatment of patients with Duchenne muscular dystrophy (DMD), amenable to exon 51 skipping. The designation is based on data from the ongoing DELIVER clinical trial...Dyne has completed enrollment of 32 patients in the Registrational Expansion Cohort of the DELIVER trial. Data from this cohort are planned for late 2025.Dyne anticipates a potential BLA submission for U.S. Accelerated Approval in early 2026."

Breakthrough therapy • Duchenne Muscular Dystrophy

DELIVER: Safety, Tolerability, Pharmacodynamic, Efficacy, and Pharmacokinetic Study of DYNE-251 in Participants With Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping (clinicaltrials.gov) - P1/2 | N=86 | Active, not recruiting | Sponsor: Dyne Therapeutics | Recruiting ➔ Active, not recruiting

Enrollment closed • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

TfR1-mediated delivery of oligonucleotides for the treatment of neuromuscular diseases: translating research into clinic (ASGCT 2025) - "We leveraged the FORCE platform to develop DYNE-101 and DYNE-251 as potential treatments for myotonic dystrophy type 1 (DM1) and Duchenne muscular dystrophy (DMD), respectively. Clinical data in both programs support the potential of the FORCE platform to deliver functional improvement in serious neuromuscular disorders."

CNS Disorders • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy • Myotonic Dystrophy • TFRC

DYNE-251 in DMD (GlobeNewswire) - "Dyne has fully enrolled the Registrational Expansion Cohort of 32 patients as part of the DELIVER trial. Data from this cohort are planned for late 2025; Dyne anticipates a potential BLA submission for U.S. Accelerated Approval in early 2026; Dyne continues to pursue expedited approval pathways globally for DYNE-251 in patients with DMD who are amenable to exon 51 skipping."

FDA filing • P1/2 data • Duchenne Muscular Dystrophy

Dyne Therapeutics Receives European Medicines Agency (EMA) Orphan Drug Designation for DYNE-251 in Duchenne Muscular Dystrophy (GlobeNewswire) - "Dyne Therapeutics, Inc...today announced that the European Commission (EC) has granted orphan drug designation for DYNE-251 for the treatment of Duchenne muscular dystrophy (DMD)....Long-term clinical data from the ongoing DELIVER trial of DYNE-251 that demonstrated unprecedented and sustained functional improvement at the selected registrational dose were presented in March at the 2025 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference....With full enrollment of the registrational expansion cohort in the DELIVER trial complete, we look forward to sharing data from this cohort in late 2025....Dyne anticipates filing a Biologics License Application (BLA) submission for US accelerated approval in early 2026."

FDA filing • Orphan drug • P1/2 data • Duchenne Muscular Dystrophy

Key Milestones for the DELIVER Trial (GlobeNewswire) - "Dyne has fully enrolled the Registrational Expansion Cohort of 32 patients as part of the DELIVER trial. Data from this cohort are planned for late 2025."

Enrollment status • P1/2 data • Duchenne Muscular Dystrophy

Dyne Therapeutics Announces New Long-Term Clinical Data from Phase 1/2 DELIVER Trial of DYNE-251 in Duchenne Muscular Dystrophy Demonstrating Unprecedented and Sustained Functional Improvement Through 18 Months (GlobeNewswire) - P1/2 | N=88 | DELIVER (NCT05524883) | Sponsor: Dyne Therapeutics | "...Updated results from the trial are being presented this week at the 2025 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference....Key findings from the DELIVER Phase 1/2 trial presentation include: Function: Meaningful and sustained improvements from baseline in multiple functional endpoints were observed in both the 20 mg/kg (selected registrational dose) and 10 mg/kg DYNE-251 Q4W cohorts, through 12 and 18 months, respectively....Starting at the 6-month timepoint, the SV95C change from baseline observed in both the 10 mg/kg and 20 mg/kg cohorts of DELIVER exceeded the published proposed minimal clinically important difference (MCID)....At the 6-month time point, patients treated with 20 mg/kg of DYNE-251 Q4W had a mean absolute dystrophin expression of 8.72% of normal (adjusted for muscle content)."

P1/2 data • Duchenne Muscular Dystrophy

Safety and Efficacy of DYNE-251 in Males with DMD Mutations Amenable to Exon 51 Skipping (AAN 2025) - P1/2 | "DYNE-251 had a favorable safety profile and resulted in early improvements across multiple functional endpoints."

Clinical • Duchenne Muscular Dystrophy • Infectious Disease

Dyne Therapeutics Reports Fourth Quarter and Full Year 2024 Financial Results and Recent Business Highlights (GlobeNewswire) - "Furthermore, in DMD, we expect data from the ongoing DELIVER trial of DYNE-251 in late 2025 to support a potential submission for U.S. Accelerated Approval in early 2026, giving us the transformational opportunity to launch two important therapies in 2027...plans to initiate a global placebo-controlled Registrational Expansion Cohort in the ACHIEVE trial that will include up to 48 patients with full enrollment planned for mid-2025 and data from this cohort planned for H1 2026."

Enrollment status • FDA filing • Launch US • P1/2 data • Duchenne Muscular Dystrophy • Myotonic Dystrophy

Dyne Therapeutics Announces Upcoming Presentations at the 2025 MDA Clinical & Scientific Conference (GlobeNewswire) - "Dyne Therapeutics...announced that the company will be presenting two oral and five poster presentations at the 2025 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference being held March 16-19, 2025, in Dallas, TX, and virtually. The oral presentations include data from the ongoing DELIVER clinical trial in Duchenne muscular dystrophy (DMD) as well as the recent positive results from the ongoing ACHIEVE clinical trial in myotonic dystrophy type 1 (DM1) which will include a summary of data on the use of splicing correction as a prognostic biomarker of functional outcomes in DM1."

Clinical data • Duchenne Muscular Dystrophy • Myotonic Dystrophy

Phase 1/2 DELIVER Trial of DYNE-251 in DMD (GlobeNewswire) - P1/2 | N=88 | DELIVER (NCT05524883) | Sponsor: Dyne Therapeutics | "Dyne reported today updated safety and tolerability data based on 54 participants enrolled in the DELIVER trial. DYNE-251 demonstrated a favorable safety profile, and the majority of treatment emergent adverse events were mild or moderate.2 The safety profile remains unchanged, and no new treatment-related serious adverse events have been observed since the prior update provided as of August 21, 2024. Approximately 837 doses have been administered to date in the DELIVER trial, representing over 65 patient-years of follow-up, with some patients followed for up to 2.2 years...Dyne is currently enrolling a 20 mg/kg (approximate PMO dose) Q4W Registrational Expansion Cohort of approximately 32 participants as part of the DELIVER trial. Dyne anticipates completion of enrollment in Q1 2025 with data from this cohort expected in late 2025."

Enrollment status • P1/2 data • Duchenne Muscular Dystrophy

DELIVER: Safety, Tolerability, Pharmacodynamic, Efficacy, and Pharmacokinetic Study of DYNE-251 in Participants With Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping (clinicaltrials.gov) - P1/2 | N=88 | Recruiting | Sponsor: Dyne Therapeutics | Trial completion date: Nov 2026 ➔ Nov 2029 | Trial primary completion date: Nov 2026 ➔ Nov 2029

Trial completion date • Trial primary completion date • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Initial Data from the DELIVER Trial of DYNE-251 in Males with DMD Mutations Amenable to Exon 51 Skipping (AAN 2024) - P1/2 | "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."

Late-breaking abstract • Anemia • Duchenne Muscular Dystrophy • Hematological Disorders • TFRC