zeleciment basivarsen (DYNE-101) / Dyne Therap - LARVOL DELTA

A translational and quantitative modeling framework for TfR-mediated delivery of gene silencing therapies for myotonic dystrophy type 1 (Neuroscience 2025) - "Parameters were translationally adjusted using physiological values and allometric scaling, and the model was used to predict PK/PD in DM1 patients participating in the AOC-1001 Phase 1/2 trial (MARINA). The same framework was applied in a reverse-translational manner, by calibrating to PK/PD data from patients receiving DYNE-101, a DMPK-targeting ASO conjugated to a Fab, in a Phase 1/2 trial (ACHIEVE), then predicting available NHP PD response...Lancet Neurol 2023, 22: 218-28 [2] www.aviditybiosciences.com/platform/publications [3] www.dyne-tx.com/our-forcetm-publications [4] Provenzano et al. J Clin Invest 2025, 135(4):e185426"

CNS Disorders • Myotonic Dystrophy

From molecular convergence to clinical divergence: Comparative pathogenic mechanisms and therapeutic trajectories in C9orf72-ALS/FTD and myotonic dystrophy. (PubMed, Neurobiol Dis) - "In contrast, RNA-targeting conjugates for DM1 (delpacibart etedesiran and DYNE-101) received FDA Breakthrough Therapy designation. Therapeutic success depends on tissue accessibility and addressing both shared and circuit-specific pathogenic cascades. While nuclear RNA targets appear druggable in myotonic dystrophy, the bidirectional transcription and compartmentalized pathology of C9orf72 ALS/FTD may require multi-targeted approaches for precision medicine."

Journal • Review • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • Genetic Disorders • Metabolic Disorders • Muscular Dystrophy • Myotonic Dystrophy • TARDBP

Dyne remains on track to initiate a confirmatory Phase 3 clinical trial in Q1 2026. (The Manila Times) - "Dyne also continues to pursue approval pathways outside of the U.S. for z-basivarsen in DM1."

New P3 trial • Regulatory • Myotonic Dystrophy

U.S. sites activated in ACHIEVE trial of zeleciment basivarsen (z-basivarsen, also known as DYNE-101) in DM1; completion of enrollment now expected in early Q2 2026 (The Manila Times) - "Dyne anticipates a potential BLA (Biologics License Application) submission for U.S. Accelerated Approval in early Q3 2027; Dyne expects a potential U.S. launch of z-basivarsen in Q1 2028, assuming FDA grants Priority Review."

FDA approval • Launch US • Trial status • Myotonic Dystrophy

Dyne Therapeutics Announces FDA Breakthrough Therapy Designation for DYNE-101 (GlobeNewswire) - "Dyne Therapeutics, Inc...today announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to DYNE-101 for the treatment of myotonic dystrophy type 1 (DM1)."

Breakthrough therapy • Myotonic Dystrophy

New Long-term Data from Multiple Ascending Dose (MAD) Portion of ACHIEVE Trial (GlobeNewswire) - P1/2 | N=104 | ACHIEVE (NCT05481879) | Sponsor: Dyne Therapeutics | "At the registrational dose of 6.8 mg/kg Q8W, DYNE-101 demonstrated robust and sustained improvement in myotonia as measured by vHOT as well as sustained improvements across multiple other endpoints; As previously disclosed, treatment with DYNE-101 led to an improvement in vHOT of 3.3 seconds as compared to placebo at 6 months; New data demonstrated that mean improvements at 6 months were sustained at 12 months for vHOT, 10MWR, 5xSTS, MDHI and QMT, which demonstrated a 10% improvement in strength at 6 months, increasing to 20% at 12 months relative to baseline; Dyne also reported updated safety and tolerability data1 from 56 patients enrolled through the 6.8 mg/kg Q8W cohort of the ACHIEVE trial. DYNE-101 continued to demonstrate a favorable safety profile, and no related serious treatment emergent adverse events have been identified."

P1/2 data • Myotonic Dystrophy

Accelerated Approval Milestones for DYNE-101 in DM1 (GlobeNewswire) - "Dyne plans to complete enrollment in the Registrational Expansion Cohort in Q4 2025; Data from this cohort are planned for mid-2026 to support a potential U.S. Accelerated Approval submission in late 2026; Dyne plans to initiate a confirmatory Phase 3 clinical trial in Q1 2026; Dyne is also pursuing expedited approval pathways globally for DYNE-101."

FDA filing • New P3 trial • P1/2 data • Trial status • Myotonic Dystrophy

Dyne Therapeutics to Host Investor Conference Call and Webcast to Provide Update on DYNE-101 for Myotonic Dystrophy Type 1, Tomorrow Tuesday, June 17 at 8:00 a.m. ET (GlobeNewswire) - "Dyne Therapeutics, Inc...today announced it plans to provide an update on DYNE-101 in myotonic dystrophy type 1 (DM1) tomorrow, June 17, 2025, and to host a webcast at 8:00 a.m. ET. The company intends to issue a press release prior to the start of the event."

Clinical • Myotonic Dystrophy

Safety and Efficacy of DYNE-101 in Adults with DM1 in the Phase 1/2 ACHIEVE Trial (ASGCT 2025) - P1/2 | "Data from the ACHIEVE trial suggest that DYNE-101 has a favorable safety profile and results in improvement in molecular biomarkers, such as CASI, that may have the ability to predict clinical outcomes in DM1. Disease Focus of Abstract:Muscle Disorders"

Clinical • P1/2 data • Alzheimer's Disease • Cognitive Disorders • Fatigue • Gastrointestinal Disorder • Genetic Disorders • Muscular Dystrophy • Myotonic Dystrophy • Pain • Pulmonary Disease • Respiratory Diseases

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-101 in DM1 (GlobeNewswire) - "Dyne participated in a Type C meeting with the Center for Drug Evaluation and Research (CDER) at the Food and Drug Administration (FDA) in May 2025 and discussed the path to regulatory approval, including U.S. Accelerated Approval, for DYNE-101 in DM1; Dyne has initiated a global placebo-controlled Registrational Expansion Cohort in the ACHIEVE trial that will include up to 48 participants with full enrollment planned for mid-2025; Data from this cohort is planned for H1 2026 to support a potential U.S. Accelerated Approval Biologics License Application (BLA) submission in H1 2026; Dyne also continues to advance preparations for a Phase 3 trial with the goal of initiating the trial in 2025; Management plans to provide a regulatory update for DYNE-101 following receipt of final FDA meeting minutes and the company’s incorporation of regulatory feedback; Dyne is also pursuing expedited approval pathways globally for DYNE-101."

FDA event • FDA filing • New P3 trial • P1/2 data • Myotonic Dystrophy

ACHIEVE: Safety, Tolerability, Pharmacodynamic, Efficacy, and Pharmacokinetic Study of DYNE-101 in Participants With Myotonic Dystrophy Type 1 (clinicaltrials.gov) - P1/2 | N=104 | Recruiting | Sponsor: Dyne Therapeutics | Trial completion date: Jul 2026 ➔ Jul 2029 | Trial primary completion date: Jul 2026 ➔ Jul 2029

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

Safety and Efficacy of DYNE-101 in Adults with DM1: Phase 1/2 ACHIEVE Trial Data (AAN 2025) - P1/2 | "DYNE-101 has a favorable safety profile and results in early improvement in molecular biomarkers and clinical outcomes in DM1."

Clinical • P1/2 data • Genetic Disorders • Muscular Dystrophy • Myotonic Dystrophy • TFRC

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

FORCE platform overcomes barriers of oligonucleotide delivery to muscle and corrects myotonic dystrophy features in preclinical models. (PubMed, Commun Med (Lond)) - "These data validate FORCE as a drug delivery platform and support the notion that DM1 may be treatable with low and infrequent dosing of DYNE-101."

Journal • Preclinical • CNS Disorders • Genetic Disorders • Muscular Dystrophy • Myotonic Dystrophy • TFRC

Dyne Therapeutics Receives FDA Fast Track Designation for DYNE-101 for the Treatment of Myotonic Dystrophy Type 1 (GlobeNewswire) - "Dyne Therapeutics, Inc...today announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for DYNE-101 for the treatment of myotonic dystrophy type 1 (DM1)....This Fast Track designation comes on the heels of robust clinical data from our ACHIEVE trial....Company Anticipates Submitting for U.S. Accelerated Approval in H1 2026"

Fast track • FDA filing • Myotonic Dystrophy

Dyne Therapeutics Reports New Clinical Data Showing Compelling Impact on Multiple Measures of Myotonic Dystrophy Type 1 (DM1) (GlobeNewswire) - P1/2 | N=104 | ACHIEVE (NCT05481879) | Sponsor: Dyne Therapeutics | "Analysis of muscle biopsy data for the 6.8 mg/kg Q8W cohort demonstrated a substantial knockdown of DMPK...Splicing correction at 3 months for the 6.8 mg/kg Q8W cohort was robust and was associated with improvement in multiple functional endpoints...Early and sustained improvement in myotonia as measured by video hand opening time (vHOT) was seen in the 6.8 mg/kg Q8W cohort, as well as at low doses with modest splicing correction, deepening with more time on drug...The majority of treatment emergent adverse events were mild or moderate, and no related serious treatment emergent adverse events have been identified...Dyne plans to initiate a global placebo-controlled Registrational Expansion Cohort in ACHIEVE...Dyne anticipates completion of enrollment of the Registrational Expansion Cohort in mid-2025 and submission for U.S. Accelerated Approval in H1 2026."

Enrollment status • FDA filing • P1/2 data • Myotonic Dystrophy

Dyne Therapeutics to Host Investor Conference Call and Webcast to Review New Clinical Data from the ACHIEVE Trial Friday, January 10 at 8:00 a.m. ET (GlobeNewswire) - "Dyne Therapeutics...announced it plans to report new clinical data from the Phase 1/2 ACHIEVE clinical trial on January 10, 2025, and to host a webcast at 8:00 a.m. ET. The company intends to issue a press release prior to the start of the event."

P1/2 data • Myotonic Dystrophy

ACHIEVE: Safety, Tolerability, Pharmacodynamic, Efficacy, and Pharmacokinetic Study of DYNE-101 in Participants With Myotonic Dystrophy Type 1 (clinicaltrials.gov) - P1/2 | N=104 | Recruiting | Sponsor: Dyne Therapeutics | N=72 ➔ 104

Enrollment change • Genetic Disorders • Muscular Dystrophy • Myotonic Dystrophy

Initial Data from the ACHIEVE Trial of DYNE-101 in Adults with Myotonic Dystrophy Type 1 (DM1) (MDA 2024) - P1/2 | "No participants demonstrated treatment-emergent anemia and there were no discontinuations. Safety and tolerability data from multiple cohorts and splicing data and analysis of the video hand opening time (vHOT) myotonia functional assessment from the 1.8 mg/kg cohort up to Week 25 will be presented."

Clinical • Anemia • CNS Disorders • Genetic Disorders • Hematological Disorders • Muscular Dystrophy • Myotonic Dystrophy • TFRC

Initial Data from the ACHIEVE Trial of DYNE-101 in Adults with Myotonic Dystrophy Type 1 (DM1) (MDA 2024) - No abstract available

Clinical • Genetic Disorders • Muscular Dystrophy • Myotonic Dystrophy

Dyne Therapeutics Receives FDA Orphan Drug Designation for DYNE-101 for the Treatment of Myotonic Dystrophy Type 1 (GlobeNewswire) - "Dyne Therapeutics, Inc...today announced that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation for DYNE-101 for the treatment of myotonic dystrophy type 1 (DM1). DYNE-101 is being evaluated in the Phase 1/2 global ACHIEVE clinical trial with initial data on safety, tolerability and splicing from the multiple ascending dose, placebo-controlled portion of the trial anticipated in the second half of 2023."

Orphan drug • P1/2 data • CNS Disorders • Myotonic Dystrophy

ACHIEVE, a Randomized, Placebo-Controlled, Multiple Ascending Dose Study of DYNE-101 in Individuals with DM1 (EAN 2023) - No abstract available

Clinical

Dyne Therapeutics Receives European Medicines Agency (EMA) Orphan Drug Designation for DYNE-101 (GlobeNewswire) - "Dyne Therapeutics, Inc...announced that the European Medicines Agency (EMA) has granted orphan drug designation for DYNE-101. DYNE-101 is being evaluated in the Phase 1/2 ACHIEVE global clinical trial in adults with myotonic dystrophy type 1 (DM1)."

Orphan drug • CNS Disorders • Muscular Atrophy • Myotonic Dystrophy